Alcohols Phenols And Ethers

Alcohols can be regarded as derivatives of hydrocarbons, saturated or unsaturated, where one or more of the hydrogens have been replaced by hydroxyl group(s).

Ethyl alcohol (C₂H₅OH) has been known since ancient times. It is an important constituent of alcoholic beverages, like beer, wine and brandy. It is also used in making tincture iodine (I₂+ C₂H₅OH), cough syrups and tonics.

Isopropyl alcohol [(CH₃)₂ CHOH] is the common ‘rubbing alcohol’ which is used as a 70% solution in water for its antibacterial properties. Methyl alcohol is widely used as an industrial solvent. Glycol is widely used as a solvent and antifreeze for fuels. Glycerol is used in medicines and cosmetics.

When the hydroxyl group is connected to a carbon atom of a benzene ring, the compound is known as a phenol. Phenols possess the general formula Ar-OH where Ar is a phenyl or substituted phenyl group. Phenol containing a small amount of water is known as carbolic acid, which is used as a disinfectant. Phenol was the firs compound to be used as an antiseptic (1867).

Phenols are considered to be different from alcohols because their chemical properties are rather different.

Ethers: Ethers are compounds in which two carbon atoms are connected to a single oxygen (C-O-C). Diethyl eth has since long been used as a general anaesthetic. It is also used as a solvent.

⇒ CH₃– O- CH₃
(Dimethyl ether)

⇒ CH₃-CH₂OCH₃
(Ethyl Methyl Ether)

If the C-O-C unit is part of a ring, the molecule is known as a cyclic ether, examples being (tetrahydrofuran) and dioxane. If the two ether-linkage carbons are directly bonded to each other to form a t-membered ring, the molecule is known as an oxirane (or epoxide).

Example 1:  Can you what petroleum ether is

Solution: Petroleum ether is in fact not an ether, but a mixture of alkanes.

Classification Alcohols Phenols And Ethers

Depending upon the number of hydroxyl groups, alcohols and phenols are classified into monohydric (one-OH group) dihydric (two-OH groups) and trihydric (three-OH groups) and polyhydric (more than three -OH groups) compounds.

Structures of some monohydric, dihydric, trihydric and polyhydric compounds:

Monohydric alcohols may be classified on the basis of the hybridisation of the carbon atom to which the hydroxyl group is attached.

Compounds Containing An Sp³ C-OH Bond

Primary, secondary and tertiary alcohols:

Monohydric alcohols are classified into primary, secondary and tertiary alcohols, depending upon the number of alkyl groups attached to the carbon atom carrying the hydroxyl group.

Thus, a primary alcohol contains a monovalent —CH₂ OH group, a secondary alcohol contains a bivalent ->CHOH group and a tertiary alcohol has a trivalent ->C-OH group.

Allyl alcohol:

In an allyl alcohol, the hydroxyl group is attached to that sp³-hybridised carbon which is bonded to the carbon-carbon double bond.

Benzyl alcohol:

In benzyl alcohol, the hydroxyl group is attached to that sp³-hybridised carbon which is bonded to the benzene ring.

Alcohols Containing An Sp² C-OH Bond

Vinyl alcohol:

In vinyl alcohol, the hydroxyl group is bonded to the sp² -hybridised carbon atom of a carbon-carbon double bond.

Phenol:

In phenol, the hydroxyl group is attached to the sp²-hybridised carbon atom of a benzene ring.

Example 2: Classify the following as primary (1°), secondary (2°) and tertiary (3°) alcohols.

Solution:  

1. 1 and 3 are primary alcohols.
2. 2 and 6 are secondary alcohols.
3. 4 and 5 are tertiary alcohols.

Ethers:

Ethers are said to be symmetrical or simple when the two alkyl groups are the same and unsymmetrical or mixed when they are different.

Symmetrical Ethers:

⇒ CH₃ – O- CH₃
(Dimethyl ether)

⇒  C₂H₅ – O-  C₂H₅
(Diethyl ether)

Unsymmetrical Ethers:

⇒  CH₃ – O- C₂H₅
(Ethyl methyl ether)

⇒  CH₃ – O- CH₂– CH₂ -CH₃
(Methyl n – propyl ether)

Nomenclature

There are three different systems of naming alcohols, and two systems of naming phenols and ethers.

Trivial name

Simple alcohols are commonly known by their trivial names or common names. According to this system, the name of an alcohol is derived by writing the name of the alkyl group and then the word alcohol. The name is always written as two separate words.

In the common system of nomenclature, the position of an additional substituent is indicated by letters of the Greek alphabet rather than by numbering, the carbon attached to the OH group being labelled α.

Any simple group that has a common name may be used in the alkyl alcohol system, with one exception. The group C₆H₅-is phenyl, but the compound C₆H₅-OH is phenol and not phenyl alcohol.

Substituted phenols are considered to be derivatives of the parent compound phenol.

However, phenyl-substituted alkyl alcohols are normal alcohols. For example,
CH₂OH

The Carbinol System

In the carbinol system, the simplest alcohol, CH₃OH, is called carbinol. More complex alcohols are considered to be alkyl-substituted carbinols. The whole name is written as one word.

The IUPAC System

Alcohols:

In the IUPAC system, alcohols are named by replacing the ‘e’ of the corresponding alkane by the suffix ‘ol’.

CH₃OH – Methane-e + ol = Methanol

CH₃CH₂OH –  Ethane-e+ol Ethanol

The positions of the hydroxyl group and other substituents are indicated by numbers, the lowest possible number being given to the carbon atom attached to the hydroxyl group.

In the IUPAC system, if two-OH groups are present in a compound (as in CH₂OH CH₂OH), the suffix becomes ‘diol’ instead of ‘ol’. If three – OH groups are present (as in CH₂OH – CHOH- CH₂OH), the suffix becomes’triol’ instead of ‘ool’. Thus:

(Note that terminal ‘e’ of the parent alkane has not been removed because the suffix ‘diol’ or triol begins with a consonant.)

Gives the common and IUPAC names of certain typical alcohols:

Monocyclic alcohols are named using the prefix cyclo and considering the -O-H group to be attached to C-1.

Phenols:

In the IUPAC system, a compound with the hydroxyl group directly attached to a benzene ring is called phenol.

Substituted phenols are named as derivatives of the parent compound phenol as illustrated by the following IUPAC names.

The common and IUPAC names of some phenols:

Ethers:

In the common system, ethers are named by first writing the names of the two alkyl groups in alphabetical order and adding the word ether.

⇒ CH₃OCH₂CH
( Ethyl Methyl Ether)

⇒  CH₃OC(CH₃)
(t-Butyl methyl ether)

In symmetrical ethers, the prefix ‘di’ is used.

Diethyl Ether

⇒ (CH₃)₂ CHOCH(CH₃)₂
(Disopropyl ether)

In the IUPAC system ethers are considered to be alkoxyalkanes. For complex molecules, the simplest organic group along with the oxygen atom is named as an alkoxy group and used as a substituent on a more complex chain.

The Common And IUPAC names of some ethers:

A few examples of IUPAC nomenclature:

Cyclic ethers are known as epoxides The term ‘epoxy’ is derived from epoxide

Example 3:  Draw the structures of the folloeing compounds.

1. 2,2,4 – Trimethyl – 3 pentanol
2. 2- Ethoxypropane
3. 5 – Methyl – 2, 4 – Hepatanediol
4. 2 – Ethyl – 6- Methylphenol
5. 2- Fluoro – 3- Methyl – 2 buten-1 – ol

Solution:

Structures of Alcohols, Ethers And Phenols

In alcohol, the hybridisation of carbon is approximately sp³. So is the hybridisation of oxygen. Oxygen share one bond with carbon and one with hydrogen. The two lone pairs of electrons on oxygen occupy orbitals that ar each approximately sp²-hybridised.

The  bond angle in an alcohol is 108.9° (a little less than the tetrahedral angle 109° 28′). This is due to the repulsion between the two lone pairs of electrons on oxygen.

In dimethyl ether the bond angle is 111.7° (a little more than the value of the tetrahedral angle). This is due to repulsion between the hydrogens marked H, in the above structural formula.

The C-O bond length of (136 pm) in phenol is slightly less than the C-O bond length (141 pm) in methanol. This is because the hydroxyl group in phenol is directly attached to the sp²-hybridised carbon of the benzene ring, which acts as an electron-withdrawing group.

General Methods Of Preparing Alcohols

Alcohols can be prepared by several methods. In this chapter, we will discuss methods which are generally used to prepare alcohols in the laboratory.

From Alkenes

By hydration:

Alcohols are prepared commercially by the hydration of alkenes (obtained cheaply from the cracking of crude oil) in the presence of an acid catalyst. The addition of a molecule of water to an alkene takes place according to the Markovnikov rule. Except for the hydration of ethylene, the reaction produces secondary and tertiary alcohols.

By hydroboration oxidation:

Alkenes react with diborane to give trialkyl boron compounds, which yield alcohols on oxidation with alkaline hydrogen peroxide.

Hydroboration Mechanism:

Because of the vacant orbital on boron, borane may be regarded as an electrophile and attacks the electrons of an alkene in accordance with the Markovnikov rule. But the chief product of the overall reaction, n-propyl alcohol, arises from the anti-Markovnikov addition of a molecule of water at the site of the double bond.

By The Hydrolysis Of Alkyl Halides

Alkyl halides can easily be hydrolysed to the corresponding alcohols by boiling with an aqueous alkali or moist silver oxide (AgOH).

The hydrolysis of alkyl halides in an aqueous alkali may occur by either the S_N1 or the S_N2 mechanism. The hydrolysis of most primary halides occurs by the S_N2 mechanism and yields alcohols in appreciable quantities.

Tertiary halides also undergo hydrolysis, but these reactions occur by the S_N1 rather than the S_N2 mechanism.

By The Reduction Of Aldehydes And Ketones

Carbonyl compounds can be reduced to the corresponding alcohols by a number of methods, either catalytically or by the use of chemical reagents.

Catalytic reduction:

Aldehydes and ketones are reduced by hydrogen in the presence of Ni, Pt or Pd catalyst at room temperature and moderate pressure to the corresponding alcohols.

⇒ \(\mathrm{RCHO} \stackrel{\mathrm{H}_2 / \mathrm{Ni}}{\longrightarrow} \mathrm{RCH}_2 \mathrm{OH}\)

During the process, the double bond is converted into a single bond.

⇒ \(\mathrm{CH}_3 \mathrm{CH}=\mathrm{CH}-\mathrm{CHO} \stackrel{\mathrm{H}_2 / \mathrm{Ni}}{\longrightarrow} \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{OH}\)

Reduction by metal hydrides:

Aldehydes and ketones are easily converted to alcohols in dry ether by LIAIH₄. LIAIH₄ is a specific reagent an does not ordinarily reduce the ethylenic double bond in the molecule to a single bond.

Sodium borohydride is a milder reducing agent and reduces aldehydes and ketones only.

⇒ \(\mathrm{CH}_3 \mathrm{CH}=\mathrm{CH}-\mathrm{CHO} \stackrel{\mathrm{Li} \mathrm{AlH}_4}{\longrightarrow} \mathrm{CH}_3 \mathrm{CH}=\mathrm{CH}-\mathrm{CH}_2 \mathrm{OH}\)

Aldehydes are reduced to primary alcohols. Ketones are reduced to secondary alcohols.

By The Reduction Of Carboxylic Acids And Esters

Carboxylic acids and esters are usually reduced by LiAlH₄ in dry ether.

In order to reduce a carboxylic acid to an alcohol, the carboxylic acid is first converted to an ester and then reduced catalytically by hydrogen to yield an alcohol.

⇒ \(\mathrm{RCOOH}+\mathrm{R}^{\prime} \mathrm{OH} \stackrel{\mathrm{H}^{+}}{\longrightarrow} \mathrm{RCOOR} \stackrel{\mathrm{H}_2}{\longrightarrow} \mathrm{RCH}_2 \mathrm{OH}+\mathrm{R}^{\prime} \mathrm{OH}\)

Grignard Reagents

Primary, secondary and tertiary alcohols can be prepared by the use of Grignard reagents.

The addition of a Grignard reagent to formaldehyde yields a primary alcohol

The addition of a Grignard reagent to formaldehyde yields a Secondary alcohol

The addition of a Grignard reagent to formaldehyde yields a Tertiary alcohol

Physical Properties Of Alcohols

The introduction of a hydroxyl group in a hydrocarbon brings about a marked change in its physical properties like melting point, boiling point and solubility in water.

Boiling point:

The boiling and melting points of alcohols show a regular increase with the increase in the number of carbon atoms. The boiling point rises by about 20 K for each additional carbon atom. This is due to the increase in van der Waals attraction. In the case of isomeric alcohols, the boiling points show a regular decrease with an increase in branching as there is a decrease in van der Waals attraction due to branching (less surface area).

The boiling points of some alcohols:

When compared to hydrocarbons, alkyl halides and ethers of comparable molecular weights the boiling points of alcohols are unusually high due to the association of their molecules through intermolecular hydrogen bonding. The high boiling point of alcohols may be attributed to the high energy required to break the hydrogen bond.

Solubility:

The lower members of the class of alcohols like methyl, ethyl, n-propyl, t-butyl and many polyhydric alcohols are completely soluble in water. This may be attributed to the intermolecular hydrogen bonding between the molecules of alcohol and water.

The solubility of alcohols decreases in water as the alkyl chain increases in length. Alcohols have both hydrophilic (waterlike, due to the OH group) and hydrophobic (alkane like, due to the carbon chain) moieties. With the increase in molecular weight, the hydrophobic character of alcohols increases. This reduces their solubility in water.

Among isomeric alcohols, tertiary alcohols are more soluble than primary and secondary alcohols. This can be attributed to a decrease in the relative volume of the hydrophobic portion.

Chemical Properties Of Alcohols

Alcohols react both as nucleophiles and electrophiles.

The O-H bond is broken when alcohols react as nucleophiles.

The reactions of alcohol can be divided into the following four types.

1. Those in which the O-H bond is cleaved,
2. Those in which the C-O bond is cleaved,
3.  Those in which the oxygen acts as a base, and
4. Oxidation.

Reactions Due To Fission Of O-H Bond

Reactions with metals-Acidic nature:

Alcohols behave as weak acids. This characteristic can be explained on the basis of the fact that the hydrogen atom is attached to the electronegative oxygen atom, which attracts the pair of electrons of the O-H bond. Due to this attraction, there is a tendency for the loss of hydrogen as a proton. Thus, alcohols react with strong electropositive metals, evolving hydrogen

The order of acid strength of various types of alcohols is primary > secondary > tertiary.

This is because oxygen is considerably more electronegative than either carbon or hydrogen. Therefore the C-O and O-H bonds are polarised towards the oxygen atom.

The tertiary alcohol is the weakest because of the presence of three electron-releasing alkyl groups on the carbon atom attached to oxygen. This increases the electron density on oxygen tending to decrease the polarity of the O-H bond. This causes a decrease in acid strength.

Reaction with Grignard reagent

Alcohols react with Grignard reagent to form alkanes.

In these reactions, the order of reactivity of alcohols is primary>Secondary> Tertiary

Esterification

Alcohols react with

1. Carboxylic acids
2. Acid halides and
3. Acid anhydrides to form esters

The reaction of an alcohol with carboxylic acid is reversible. It is catalysed by concentrated H₂SO₄. Concentrated H₂SO₄ removes water as soon as it is formed so that the forward reaction is favoured.

Esterification Mechanism:

The reaction of an alcohol with an acid chloride occurs rapidly and does not require an acid catalyst. Pyridine (a base) is usually added to the reaction mixture to neutralise HCl as soon as it is formed during the reaction. Alcohols react with acid anhydrides to form esters in the absence of a catalyst.

Reactions Of Alcohols Involving C-O Bond Cleavage

Formation of an alkyl halide

Alcohols react with a variety of reagents to yield alkyl halides. The most commonly used reagents are hydrogen halides (HCl, HBr or HI), phosphorus tribromide (PBr₃) and thionyl chloride (SOCI₂).

Reactions with hydrogen halides

Alcohols react with dry HCl(g) in the presence of anhydrous ZnCl₂ as a catalyst. CH₃CH₂OH + HCl(g)- anhydrous →CH₃CH₂Cl+ H₂O ZnCl₂ Ethyl chloride (chloroethane)

Hydrogen halides Mechanism

Lucas reagent

Low-molecular-weight primary, secondary and tertiary alcohols react at different rates with a solution of anhydrous zinc chloride in concentrated hydrochloric acid (Lucas reagent) (alcohols are soluble in the Lucas reagent) to give alkyl halides which are not soluble in the reaction mixture and can be seen as a separate oily layer (and on shaking give a cloudy appearance).

The ease with which the alkyl halide forms depends upon the ease with which the alcohol is converted into a carbocation. Tertiary alcohols react instantly, secondary alcohol within two or three minutes, and primary alcohols do not produce turbidity at room temperature.

The difference in reaction rates described above is the basis of the Lucas test by means of which primary, secondary and tertiary alcohols are distinguished.

Alcohols react with HBr (formed by the reaction between KBr and concentrated H₂SO₄) to yield alkyl bromides.

Alcohols give alkyl iodides on reaction with hydrogen iodide.

Reaction with phosphorus halides

Alcohols react with phosphorus halides to form alkyl halides.

⇒ \(\mathrm{R}-\mathrm{OH}+\mathrm{PX}_5 \rightarrow \mathrm{RX}+\mathrm{POX}_3+\mathrm{HX}\)

⇒ \(3 \mathrm{R}-\mathrm{OH}+\mathrm{PX}_3 \rightarrow 3 \mathrm{RX}+\mathrm{H}_3 \mathrm{PO}_3\)

For example:

⇒ \(\mathrm{C}_2 \mathrm{H}_5 \mathrm{OH}+\mathrm{PCl}_5 \rightarrow \underset{\text { Ethyl chloride }}{\mathrm{C}_2 \mathrm{H}_5 \mathrm{Cl}}+\mathrm{POCl}_3+\mathrm{HCl}\)

⇒ \(3 \mathrm{C}_2 \mathrm{H}_5 \mathrm{OH}+\underset{\left(2 \mathrm{P}+3 \mathrm{Br}_2\right)}{\mathrm{PBr}_3} \rightarrow \underset{\text { Ethyl bromide }}{3 \mathrm{C}_2 \mathrm{H}_5 \mathrm{Br}}+\mathrm{H}_3 \mathrm{PO}_3\)

⇒ \(3 \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{OH}+\mathrm{PI}_3 \rightarrow \underset{\text { Ethyl iodide }}{3 \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{I}}+\mathrm{H}_3 \mathrm{PO}_3\)

Victor Meyer Test (Distinction between primary, secondary and tertiary alcohols):

Reaction with thionyl chloride

Alcohols react with thionyl chloride in the presence of pyridine to form alkyl chlorides.

⇒ \(\mathrm{ROH}+\underset{\begin{array}{c}
\text { Thionyl } \\
\text { chloride }
\end{array}}{\mathrm{SOCl}_2} \stackrel{\text { Pyridine }}{\longrightarrow} \mathrm{RCl}+\underbrace{\mathrm{SO}_2+\mathrm{HCl}}_{\text {gas }}\)

⇒ \(\mathrm{CH}_3 \mathrm{CH}_2 \mathrm{OH}+\mathrm{SOCl}_2 \stackrel{\text { Pyridine }}{\longrightarrow} \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{Cl}+3 \mathrm{SO}_2 \uparrow+\mathrm{HCl} \uparrow\)

Reaction with concentrated H₂SO₄

Like other acids, concentrated H₂SO₄ also reacts with an alcohol to form an ester (alkyl hydrogen sulphate).

Reaction with Ammonia:

A mixture of primary, secondary and tertiary amines is formed when vapours of alcohol and ammonia are passed through heated alumina at 633 K.

Dehydration

Alcohols can easily be dehydrated to olefins at high temperatures in the presence of an acid

This is a ẞ-elimination reaction and is favoured by high temperature.

An elimination reaction in which a proton is lost from one carbon (B-carbon) and a nucleophile is lost from the adjacent carbon (a-carbon) is called a -elimination reaction or 1, 2-elimination reaction. The most common examples of B-elimination reactions include the dehydrohalogenation of alkyl halides and the dehydration of alcohols

In order of decreasing acidity, the acids commonly used in the reaction are H₂SO₄>H₃PO₄ >(COOH)₂ >HCOOH> KHSO₄ > Al₂O₃

The dehydration of primary alcohols requires a higher temperature than is needed for the dehydration of secondary or tertiary alcohols.

Secondary alcohols undergo dehydration in milder conditions.

Tertiary alcohols undergo dehydration at a much lower temperature.

Thus, the relative ease with which alcohols undergo dehydration is in the following order.

Dehydration Mechanism:

In case the olefin concerned has an isomer, the more stable isomer is formed (Saytzev rule).

Some Primary and secondary alcohols undergo rearrangement during dehydration. For example,

Oxidation And Dehydrogenation Of Alcohols

The oxidation of alcohol takes place with the cleavage of O-H and C-H bonds to form the C = O bond.

This type of cleavage and formation of bonds occurs in oxidation and dehydrogenation reactions.

Primary, secondary and tertiary alcohols differ in their behaviour towards oxidising agents. In general, primary alcohols yield aldehydes, which are readily oxidised further to carboxylic acids. Secondary alcohols give ketones, which are relatively resistant to further oxidation.

Tertiary alcohols do not have a hydrogen atom on the carbon attached to the hydroxyl group and are resistant to oxidation.

The orange-red colour of a solution of chromic anhydride (CrO₃ in aqueous sulphuric acid) is immediately discharged when this solution is added dropwise to a solution of a primary or secondary alcohol in acetone. Tertiary alcohols fail to react immediately.

Reactions of primary, secondary and tertiary alcohols with CrO₃ in aqueous H₂SO₄:

Acidic or basic aqueous potassium permanganate is often used to oxidise primary alcohols to carboxylic acids directly.

⇒ \(\mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{OH} \frac{\mathrm{KMnO}_4 / \mathrm{H}_2 \mathrm{SO}_4}{[\mathrm{O}]} \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{COOH}\)

Tertiary alcohols are not easily oxidised by acidified KMnO4. However, at elevated temperatures, the use of strong oxidising agents (acidified KMnO₄ ) leads to the breaking of C-C bonds and the formation of a carboxylic acid containing a fewer number of carbons.

Primary alcohols are mainly oxidised to aldehydes by a weak oxidising agent, pyridinium chloromate (PCC).

⇒ \(\mathrm{R}-\mathrm{CH}_2-\mathrm{OH} \underset{[\mathrm{O}]}{\stackrel{\mathrm{PCC}}{\longrightarrow}} \mathrm{R}-\mathrm{CHO}\)

Pyridinium chlorochromate is a complex compound of chromium trioxide, pyridine and concentrated HCl.

This compound oxidises a primary alcohol to an aldehyde and the reaction stops at this stage. Pyridinium chlorochromate does not attack double bonds.

When alcohol vapour is passed over copper at 573 K, dehydrogenation occurs; a primary alcohol yields an aldehyde and a secondary alcohol yields a ketone. A tertiary alcohol undergoes dehydration to yield an alkene.

⇒ \(\mathrm{CH}_3-\mathrm{CH}_2-\mathrm{OH} \underset{573 \mathrm{~K}}{\stackrel{\mathrm{Cu}}{\longrightarrow}} \underset{\text { Acetaldehyde }}{\mathrm{CH}_3-\mathrm{CHO}}+\mathrm{H}_2\)

⇒ \(\underset{\text { Isopropyl alcohol }}{\mathrm{CH}_3 \mathrm{CHOHCH}_3} \underset{573 \mathrm{~K}}{\stackrel{\mathrm{Cu}}{\longrightarrow}} \underset{\text { Acetone }}{\mathrm{CH}_3 \mathrm{COCH}_3}+\mathrm{H}_2\)

This reaction may be used for differentiating primary, secondary and tertiary alcohols.

Example 4: Give the structures of the products of the following reactions. Give reasons for your answer.

Solution:

This is an electrophilic addition reaction. In an acid medium water adds according to the Markovnikov rule.

NaBH₄ is a weak reducing agent>It reduces the ketonic group selectively.

This s the nucleophilic addition reaction of a Grignard regent with a carbonyl compound

Some Commercially Important Alcohols

Methanol

Methanol is known as wood alcohol or wood spirit because it was first obtained by the destructive distillation of wood. Today methanol is produced commercially by passing a mixture of carbon monoxide and hydrogen over a catalyst containing oxides of chromium, copper and zinc at a temperature of 623-723 K and a pressure of 200 atm.

Methanol is highly toxic. Ingestion of even small quantities of methanol can cause blindness; large quantities cause death. It is used as a laboratory reagent and as a solvent for paints and varnishes. It is also used in the preparation of formaldehyde.

Ethanol

Ethanol is manufactured on a large scale from molasses, a brown syrup prepared from raw sugar during the sugar-manufacturing process. Molasses is diluted with water whereby some of the cane sugar dissolves. The diluted solution is fermented with yeast.

The enzymes invertase and zymase are present in yeast. Invertase converts sugar into a mixture of the isomers glucose and fructose. Zymase converts this mixture into ethanol and carbon dioxide. After fermentation is over the alcohol is distilled. The alcohol so obtained is 95% pure, the rest being water. This is referred to as rectified spirit.

⇒  \(\mathrm{C}_{12} \mathrm{H}_{22} \mathrm{O}_{11}+\mathrm{H}_2 \mathrm{O} \stackrel{\text { invertase }}{\longrightarrow} \underset{\text { Glucose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}+\underset{\text { Fructose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}\)

⇒ \(\underset{\text { Glucose and fructose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6} \stackrel{\text { zymase }}{\longrightarrow} \underset{\text { Ethyl alcohol (ethanol) }}{2 \mathrm{C}_2 \mathrm{H}_5 \mathrm{OH}}+2 \mathrm{CO}_2\)

Pure ethanol (absolute alcohol) cannot be obtained by fractionation. It is difficult and expensive to remove the last traces of water. Water can be removed by distilling the rectified spirit with anhydrous benzene. A ternary azeotropic mixture of 7.5% water, 18.5% alcohol and 74% benzene is formed, which distils out first. The residual liquid in the distilling flask is absolute alcohol (99.9%).

The last traces of water can be removed by distilling it over metallic magnesium. Absolute alcohol is hygroscopic and should be carefully preserved away from moisture. Rectified spirit and absolute alcohol, like alcoholic drinks, are taxed at a very high rate. For many industrial purposes pure alcohol is not needed and it is made undrinkable by adding various other chemicals.

This industrial methylated spirit or denatured alcohol is a mixture of 95% rectified spirit and 5% methanol, which is extremely poisonous. Sometimes CuSO₄ is added to give a blue colour to methylated spirit, so that people do not drink it by mistake. Alcohol is mainly used as a solvent for paints, varnishes, perfurmes, and so on. It may be a useful fuel some day, since it burns to form CO₂ and water, producing a considerable amount of heat.

Wine production

• Wine is made from grapes, which contain sugar. The grapes are crushed to squeeze out the juice. A fungus (yeast) grows naturally on the skins of the grapes. Its enzymes start the fermentation of the sugar in the juice as soon as the grapes have been crushed.
• Fermentation is carried out in the absence of air (anaerobic condition). This is because the oxygen of air oxidises ethanol to acetic acid, which destroys the taste of alcoholic drinks.
• Fermentation is complete when all the sugar has been converted into alcohol after several days. The wine is stored for several months, or even years, to mature before being bottled for sale.
• Red wine is produced from black grapes by mixing some of the skins of black grapes into the juice during fermentation so that the colouring matter from the skins passes into the wine. Sparkling wines, like champagne, are made by bottling the wine before fermentation is complete. Fermentation continues inside the bottle and the carbon dioxide produced dissolves in the wine.
• When the bottle is opened, the pressure is released and the carbon dioxide bubbles out slowly. Wine contains between 10% and 12% of alcohol by weight. To make stronger wines like sherry and port, brandy (34% of alcohol by weight) is added to increase the ethanol content to about 17% by weight. The average strengths of some alcoholic drinks are given in the following table.

The alcohol content of some common alcoholic drinks:

The effects of alcohol on the body

In small quantities, ethyl alcohol (generally called alcohol) is a stimulant and can be beneficial. In small quantities, alcohol increases the flow of the digestive juices and stimulates the appetite. In larger quantities, alcohol makes the whole nervous system less sensitive. An excessive intake of alcohol over a long period can cause addiction (alcoholism), affect the liver and kidneys, and eventually cause damage to the brain.

Phenols

Phenol was discovered in the middle oil fraction during the distillation of coal tar sometime in the nineteenth century and was named carbolic acid.

Phenol Methods of Preparation

Phenol is prepared by the following methods.

1. Laboratory methods:

From benzene diazonium salts: Aniline is diazotised with NaNO₂ and HCl at 0-5°C (278 K) and the resulting benzene diazonium salt forms phenol with water.

From benzene sulphonic acid:  The fusion of the sodium salt of benzene sulphonic acid with solid NaOH at 623 K followed by acidification yields phenol.

From chlorobenzene: Chlorobenzene reacts with aqueous sodium hydroxide solution at 623 K and 300 atm to produce sodium phenoxide, which on acidification yields phenol.

2. Commercial method (from cumene):

The oxidation of isopropylbenzene (cumene) with air in the presence of an acid catalyst (H₂SO₄) gives cumene hydroperoxide which on hydrolysis with an acid yields phenol and acetone.

Cumene itself is prepared by the Friedel-Crafts alkylation of benzene with propyl chloride

Physical Properties of Phenols

Phenol is a colourless, crystalline, low-melting (315 K) solid. The O-H bond of phenol is polar and therefore involved in intermolecular hydrogen bonding as shown below.

Due to intermolecular hydrogen bonding, the boiling point of phenol (455 K) is higher than that of toluer (383 K), which has a comparable molecular weight.

Phenol is moderately soluble in water because it forms hydrogen bonds with water.

Chemical Properties of Phenols

Reactions of the phenolic (-OH) group

Acidic nature:  The acidic nature of phenol is indicated by the following reactions.

1. Phenol turns blue litmus red.

2. Phenol reacts with sodium metal to evolve hydrogen gas.

⇒ 2C₆H₅OH + 2Na →2C₆H₅ONa+ H₂

3. Phenol reacts with sodium hydroxide to give sodium phenoxide.

⇒ C₆H₅ OH + NaOH→ C₆H₅ONa+ H₂O

4. Phenols fail to react with Na₂CO₃ or NaHCO₃. In fact, phenols are precipitated from an aq solution of sodium phenoxide by bubbling CO₂ gas.

⇒ C₆H₅ONa + CO₂+ H₂O→ C₆H₅OH+NaHCO₃

The hydroxyl group of phenol is directly attached to the sp²-hybridised carbon of the benzene ring. Due to the higher electronegativity of the sp²-hybridised carbon of phenol, the electron density decreases on the oxygen atom. This increases the polarisation of the O-H bond and results in an increase in the ionisation of phenol.

The negative charge on the oxygen atom of the phenoxide anion gets delocalised in the benzene ring. This delocalisation makes the phenoxide anion more stable and favours the ionisation of phenol.

The delocalisation, no doubt, is also possible in phenol as shown below.

As these resonating structures involve charge separation, phenol is much less stable than the phenoxide anion. The presence of an electron-withdrawing group (NO₂) at the o and p positions enhances the acidic strength of phenol.Thus, p-nitrophenol is more acidic than phenol. On the other hand, an electron-releasing group attached to the benzene ring decreases the acid strength. Cresols, for example, are less acidic than phenol.

Phenol is more acidic than ethyl alcohol. Let us see how.

Phenol is soluble in aqueous sodium hydroxide solution and forms sodium phenoxide. Ethyl alcohol, on the other hand, does not react at all with sodium hydroxide.

In phenol, the hydroxyl group is bonded directly to an sp²-hybridised carbon atom of the aromatic ring. Being more electronegative than the sp³-hybridised carbon, the sp²-hybridised carbon polarises the O-H bond. This means that the ionisation of phenol is greater than that of ethyl alcohol (in which the OH group is attached to a -hybridised carbon).

The greater acidity of phenol as compared to ethyl alcohol is attributed to the greater stability of the phenoxide anion than that of the ethoxide anion. In the ethoxide (C₂H₅, O^–) anion, the full negative charge is localised on the oxygen atom and therefore the anion is not stable.

As a consequence, this anion is strongly basic and the corresponding acid (C₂ H₅ OH) is very weak. On the other hand, in the phenoxide anion, the negative charge is delocalised over the entire molecule as shown below.

The delocalisation of charge stabilises the phenoxide anion and favours ionisation of the phenol to the phenoxide anion and H.

pk, values of some phenols and ethanol:

The greater the pK, value, the weaker the acid.

Reaction with Zn dust:

On distillation with Zn dust, phenol is converted to benzene.

⇒ C₆H₅OH + Zn→ C₆H₆ + ZnO

Alkylation The sodium salt of phenol (sodium phenoxide) reacts with an alkyl halide to form the corresponding ether.

Acylation Phenol reacts with acetyl chloride in the presence of pyridine (a base) to yield phenyl acetate

Reaction with Ammonia

Phenol reacts with ammonia at 573 K in the presence of anhydrous ZnCI₂ to yield aniline.

Reaction with phosphorus pentachloride:

On treatment with phosphorus pentachloride, phenol gives chlorobenzene (poor yield)

⇒ C₆H₅OH+ PCI₅→ C₆H₅CI+ HCI (Chlorobenzene)

Mainly, triphenyl phosphate is formed in the side reaction.

⇒ 3C₆H₆OH + POCI₆ → (C₆H₅)₃ PO₄ +3HCI Triphenyl phosphate

Substitution reactions in the benzene nucleus

The presence of the OH group in phenols activates the benzene ring and electrophilic substitution becomes possible. Phenols undergo electrophilic substitution reactions more readily than benzene. The hydroxyl group directs the incoming group to ortho- and para-positions as these positions become electron-rich.

Phenol undergoes nitration, halogenation, sulphonation and Friedel-Crafts reaction readily.

Nitration Phenol can be nitrated in dilute aqueous nitric acid even at room temperature. Ortho- as well as para- para-nitrophenols are formed.

The ortho- and para-isomers can be separated by steam distillation. o-nitrophenol is steam volatile. It has higher volatility because of the intramolecular hydrogen bonding between the hydroxyl group and the nitro group.

p-nitrophenol is less volatile because intermolecular hydrogen bonding causes association between its molecules. Thus, o-nitrophenol passes over with the steam, and p-nitrophenol remains in the distillation flask.

Phenol is first sulfonated and then nitrated to form picric acid. It is not treated with nitric acid first because phenol is easily oxidised by nitric acid.

Halogenation: When bromine water is added to phenol, a white precipitate of 2, 4, 6-tribromophenol is formed

Bromination in a nonpolar solvent (carbon disulphide) affords p-bromophenol as the main product.

Halogenation takes place even in the absence of a Lewis acid because the hydroxyl group in phenol activates the benzene ring towards electrophilic substitution.

Sulphonation:

Phenol reacts with concentrated H₂SO₄, to form a mixture of ortho- and para-hydroxybenzene sulphonic acid. At higher temperatures, predominantly the p-isomer is formed because it is less reactive than the ortho-isomer due to less steric interference of the bulky sulphonic acid group.

Friedel-Crafts reaction: 

Phenol reacts with methyl chloride in the presence of anhydrous AICI₃ to give o-cresol and p-cresol.

Kolbe reaction:

On being heated with CO₂ at 393-413 K and 1.5 atm the sodium salt of phenol yields the sodium salt of salicylic acid. On acidification, the latter salt gives salicylic acid. This entire sequence of reactions comprises what is known as the Kolbe reaction.

Reimer-Tiemann reaction:

On being heated with chloroform and caustic alkali, phenol gives salicylaldehyde.

In this reaction, dichlorocarbene (: CCl₂) is a reactive intermediate, which is formed by the alkaline hydrolysis of chloroform.

⇒ \(\stackrel{\ominus}{\mathrm{O}}+\mathrm{H}-\mathrm{CCl}_3 \rightleftharpoons \mathrm{H}_2 \mathrm{O}+: \stackrel{\ominus}{\mathrm{C}} \mathrm{Cl}_3 \rightarrow \stackrel{\ominus}{\mathrm{C}}+: \mathrm{CCl}_2\)

: CCl₂ is an electrophilic reagent. It reacts with the phenoxide anion to form salicylaldehyde

Coupling reaction: In the presence of an alkali, phenol couples with benzene diazonium chloride to form p-hydroxy azobenzene, which is a red dye.

Reaction with phthalic anhydride:

On being heated with phthalic anhydride in the presence of concentrated H₂SO₄, phenol gives phenolphthalein. Phenolphthalein gives a red colour with an alkali. It is used as an indicator in acid-base titration.

Reaction with FeCl₃: On treatment with a neutral FeCl3 solution, phenol gives a violet colouration. The violet colour is due to the formation of a water-soluble iron complex.

6C₆H₅OH + FeCl₃ →3H⁺ [Fe(OC₆H₅)₆]^-3+3HCl [complex ion (violet)]

This reaction is used as a test for the presence of phenol.

Liebermann’s nitroso reaction:

Phenol forms a deep blue solution on treatment with sodium nitrite and concentrated H₂SO₄ in cold conditions.

The colour turns red when the solution is diluted with water. The red solution becomes blue when it is made alkaline. This reaction is known as Liebermann’s nitroso reaction and is used as a test for the presence of phenol.

Oxidation:  On oxidation with chromic acid, phenol gives benzoquinone.

Phenol Uses

Phenol is used in the preparation of

1. Bakelite (synthetic resin),
2. Picric acid (as an explosive),
3. Phenolphthalein (as an indicator), and
4. Salol, aspirin, salicylic acid (as drugs).

Ethers

Ethers Methods of preparation

By the dehydration of alcohol:

Ethers are usually prepared by heating alcohols with concentrated H₂SO₄.

⇒ \(2 \mathrm{ROH} \stackrel{\Delta, \mathrm{H}_2 \mathrm{SO}_4}{\longrightarrow} \mathrm{R}-\mathrm{O}-\mathrm{R}+\mathrm{H}_2 \mathrm{O}\)

Diethyl ether is prepared by heating ethyl alcohol with concentrated H₂SO₄ at 413 K. The reaction occurs in two steps. At a low temperature, ethyl alcohol reacts with concentrated H₂SO₄ to form ethyl hydrogen sulphate which again reacts with ethyl alcohol at 413 K to yield diethyl ether

Ethers Mechanism

This is a nucleophilic bimolecular substitution (SN₂) reaction.

This method is only used in the preparation of ethers having unhindered primary alkyl group dehydration secondary or tertiary alcohols, yield alkenes as elimination competes with substitution.

From alcohol vapours and heated alumina:

Diethyl ether is formed when vapours of alcohol are passed through heated alumina at 513-533 K. anhydrous

⇒ \(\mathrm{CH}_3-\mathrm{CH}_2-\mathrm{OH}+\mathrm{H} \mathrm{O}-\mathrm{CH}_2-\mathrm{CH}_3 \frac{\text { anhydrous } \mathrm{Al}_2 \mathrm{O}_3}{513-533 \mathrm{~K}} \mathrm{CH}_3-\mathrm{CH}_2-\mathrm{O}-\mathrm{CH}_2-\mathrm{CH}_3+\mathrm{H}_2 \mathrm{O}\)

By Williamson Synthesis

Diethyl ether is formed when ethyl iodide is heated with an alcoholic solution of sodium ethoxide. (produced by the action of sodium on ethyl alcohol).

⇒ \(\mathrm{CH}_3-\mathrm{CH}_2-\mathrm{I}+\mathrm{Na}-\mathrm{O}-\mathrm{CH}_2-\mathrm{CH}_3 \rightarrow \mathrm{CH}_3-\underset{\text { Diedium ethoxide }}{\mathrm{CH}_2-\mathrm{O}-\mathrm{CH}_2-\mathrm{CH}_3+\mathrm{NaI}}\)

This is an example of Williamson’s synthesis.

 Williamson’s synthesis Mechanism

Williamson synthesis involves the displacement of a halide ion from an alkyl halide by an alkoxide. It follows the S_N2 mechanism.

Symmetrical as well as unsymmetrical ethers can be synthesised. However, the alkyl halide must be a primary alkyl halide. For example, sodium f-butoxide reacts with methyl bromide to yield t-butyl methyl ether.

If a tertiary alkyl halide is treated with sodium ethoxide, then an alkene is formed due to the dehydrohalogenation of the alkyl halide. For example, the reaction of CH₃CH₂ONa with (CH₃)₃ C-Br gives 2-methylpropene exclusively.

The ethoxide anion (a strong base) reacts with t-butyl bromide, leading to an elimination reaction. Phenol can also be converted into an ether by Williamson synthesis.

From an alkyl halide and dry silver oxide:

Diethyl ether is formed on heating ethyl iodide with dry silver oxide.

⇒ \(2 \mathrm{CH}_3-\mathrm{CH}_2-\mathrm{I}+\mathrm{Ag}_2 \mathrm{O} \rightarrow \mathrm{CH}_3-\mathrm{CH}_2-\mathrm{O}-\mathrm{CH}_2-\mathrm{CH}_3+2 \mathrm{AgI}\)

Physical Properties of Ethers

Diethyl ether is a colourless, volatile liquid. The C–O bonds in ethers are polar and ethers do have a dipole noment (for diethyl ether, HD = 1.18), revealing the angular nature of the molecule. The bond angle in diethyl ther is around 110°.

Boiling point:

Ethers have lower boiling points than the corresponding isomeric alcohols since there is no association between the molecules due to hydrogen bonding. The boiling points of ethers are close to those of alkanes of comparable molecular weight.

Solubility:

The rule of thumb which states that compounds having no more than four carbons per oxygen are water-soluble holds for ethers as well as for alcohols. The solubility of ethers in water is comparable to that of alcohols of nearly the same molecular weights. The solubility of diethyl ether and 1-butanol is about 10 g per 100 g of H₂O at 298 K. This is because of their capability to form hydrogen bonds with water.

Chemical Properties of Ethers

Ethers are relatively inert to most reagents. They are stable to bases, to catalytic hydrogenation, and to most other reducing agents.

Reactions with acids

Ethers are stable to dilute acids but do react with hot concentrated acids. Strong HBr or HI causes cleavage of the C-O bond in ethers.

Reaction with HI:

Two molecules of an alkyl iodide are formed when an ether is boiled with HI. Initially a molecule of an alcohol is also formed, which reacts further to form a second molecule of an alkyl iodide.

⇒ \(\mathrm{C}_2 \mathrm{H}_5-\mathrm{O}-\mathrm{C}_2 \mathrm{H}_5+2 \mathrm{HI} \stackrel{\Delta}{\longrightarrow} 2 \mathrm{C}_2 \mathrm{H}_5 \mathrm{I}+\mathrm{H}_2 \mathrm{O}\)

 Ether Mechanism:

The ether first dissolves in the acid due to its basic nature with the formation of an oxonium ion. This is followed by an S_N2 reaction with the iodide ion.

In the next step, the ethyl alcohol formed reacts with HI to produce a second mole of ethyl iodide.

In the case of an unsymmetrical ether, the iodide ion (a nucleophile) attacks the least substituted carbon (carbon the smaller alkyl group) of the oxonium ion and displaces an alcohol molecule by the S_N2 mechanism.

At High Temperature, the excess HI reacts with Ethyl Alcohol to yield ethyl iodide

However, when one of the alkyl groups is the tertiary butyl group, the iodide formed is t-butyl iodide through the S 1 mechanism. In this reaction, the nucleophilic iodide ion attacks the more substituted carbon (carbon of the bigger alkyl group i.e.,

Anisole (an aromatic ether) reacts with HI to form methyl iodide and phenol. Alkyl aryl ethers are cleaved at the alkyl-oxygen bond because neither S_N1 nor S_N2 processes can normally occur at the aromatic carbon. The phenyl group is electron-rich and tends to repel any nucleophile.

Phenol does not react further to give a halide as the nucleophilic substitution reaction of phenol is rather difficult.

The C-O bond in ethers can also be cleaved upon their reactions with HBr and with HCl. Since these acids are less reactive than HI (because CI and Br are poorer nucleophiles than I), higher concentrations and temperatures are required for them to be effective.

The cyclic ether tetrahydrofuran is cleaved by HCI in the presence of ZnCl₂ to yield 1, 4 dichlorobutane, a valuable intermediate in the manufacture of nylon.

Reaction due to ethereal oxygen:

Ethers are bases and can react with acids such as sulphuric acid, boron trifluoride, and Grignard reagents.

Auto – Oxidation:

Ethers react with atmospheric oxygen to form peroxides

Peroxides explode violently on heating. During the distillation of an ether, the residue in the distilling flask becomes rich in peroxides. Therefore, ethers should not be distilled to dryness.
The presence of peroxide in an ether can be detected by shaking a small volume of an ether mixed with an aqueous KI solution.  A purple colour confirms the presence of peroxide.

Electrophilic substitution reactions:

The alkoxy group (OR) activates the benzene ring towards electrophilic substitution. It directs the incoming group to ortho- and para-positions as these positions become electron-rich as shown below.

Halogenation:  Bromination of anisole (methyl phenyl ether) in an acetic acid medium mainly gives p-bromoanisole

Nitration:  In the presence of concentrated H₂SO₄, anisole reacts with concentrated HNO₃ at 323-333 K to give ortho- and para- para-nitro anisole.

Friedel-Crafts reaction:  Anisole reacts with an alkyl halide or acyl halide in the presence of anhydrous AICI₃ as a catalyst. The alkyl or acyl groups are introduced at the ortho- and para-positions

Example 5: Give the structures of the products of the following reactions. Explain your answers.

Solution:

This is an S_N2 reaction. The nucleophile Br attacks the less substituted alkyl group.

In this case, the nucleophile (I) cannot attack the electron-rich carbon of benzene. It preferentially attacks the more stable tertiary carbonium ion.

This is an electrophilic aromatic substitution reaction. Since the OCH, group is o- and p- directing, NO₂ (HNO₃ + 2H₂SO₄→2HSO₄ + NO₂ + H₂O) is substituted at the o- and p-positions.

This is an S_N2 reaction. The nucleophile Br attacks the less-substituted alkyl group.

Alcohols Phenols And Ethers Multiple-Choice Questions

Question 1. Glycerol is a

1. Monohydric alcohol
2. Trihydric alcohol
3. Dihydric alcohol
4. None of these

Answer: 3. Dihydric alcohol

Question 2. Methyl alcohol and ethyl alcohol are distinguished by the reaction with

1. I₂/NaOH
2. Na
3. CH₃COOH
4. None of these

Answer: 1. I₂/NaOH

Question 3. C₂H₂OH and CH₃-O-CH, are

1. Position isomers
2. Chain isomers
3. Functional isomers
4. Metamers

Answer: 2. Functional isomers

Question 4. Which of the following compounds will give an ester with an acid?

1. Paraffin
2. Alcohol
3. Alkene
4. Alkyl halide

Answer: 2. Alcohol

Question 5. The first component formed on the oxidation of a primary alcohol is a/an

1. Ketone
2. Ester
3. Carboxylic acid
4. Aldehyde

Answer: 4. Aldehyde

Question 6. Alcohols contains the functional group

1. -OH
2. -CHO
3. C=O
4. -NH₂

Answer: 1. -OH

Question 7. Lucas reagent is

1. Concentrated HCl + anhydrous ZnCl₂
2. Dilute HCl + Hydrated ZnCl₂
3. Concentrated HNO₃+ anhydrous ZnCl₂
4. Concentrated HNO₃ + anhydrous MgCl₂

Answer: 1. Concentrated HCl + anhydrous ZnCl₂

Question 8. Ethanol and methanol are distinguished by

1. The chloroform test
2. The Victor Meyer test
3. Their rates of esterification
4. The iodoform test

Answer: 4. The iodoform test

Question 9. A primary alcohol contains a

1. CHOH group
2. -CH₂OH
3. ->C-OH group
4. None of these

Answer: 2. -CH₂OH

Question 10. On distillation with zinc, phenol gives

1. Nitrobenzene
2. Aniline
3. Benzene
4. Zinc Phenoxide

Answer: 3. Benzene

Question 11. On reaction with bromine-water, phenol gives

1. Bromobenzene
2. Dibromorphenol
3. 2,4,6 – tribromophenol
4. Picric acid

Answer: 3. 2,4,6 – tribromophenol

Question 12. Methyl propyl ether is

1. Asymmetrical ether
2. An unsymmetrical ether
3. A simple ether
4. None of these

Answer: 2. An unsymmetrical ether

Question 13. In reaction with a mineral acid, an ether gives an

1. Oxonium salt
2. Ether peroxide
3. Alkane
4. Aldehyde

Answer: 1. Oxonium salt

Question 14. Diethyl ether and methyl propyl ether are

1. Functional isomers
2. Metamers
3. Position isomers
4. Chain isomers

Answer: 2. Metamers

Question 15. The IUPAC name of CH₃OC₂H₅ is

1. Methoxy ethane
2. Propoxymetane
3. Ethyl methyl ether
4. Diethyl ether

Answer:  1. Methoxy ethane

Question 16. To prepare diethyl ether, bromoethane is heated with which of the following compounds?

1. Ethanol
2. Sodium ethoxide in dry ether
3. C₂H₂OH/Na
4. HI

Answer: 2. Sodium ethoxide in dry ether

Question 17. Diethyl ether and 1-butanol are

1. Position isomers
2. Functional Isomers
3. Optical isomers
4. Metamers

Answer: 2. Functional Isomers

Question 18. The correct order of the boiling points of primary (1), secondary (2°) and tertiary (3°) alcohols is

1. 1°> 2° >3°
2. 3° 2° 1°
3. 2>1° >30
4. 2° >30 > 1°

Answer: 1. 1°> 2° >3°

Question 19. Among the following, which is the most acidic?

1. Phenol
2. Benzyl alcohol
3. m-Chlorophenol
4. Cyclohexanol

Answer: 1. Phenol

Question 20. Which of the following forms hydrogen bonds to a greater extent?

1. Ethanol
2. Diethyl ether
3. Triethyl amine
4. Ethyl chloride

Answer: 1. Ethanol

Question 21. Which of the following will respond positively to the iodoform test?

1. CH₂OH
2. (CH₃)₂CHOH
3. (CH₃), COH
4. CH₃ OH

Answer:  2. (CH₃)₂CHOH

Question 22. Formaldehyde reacts with CH₃MgBr to give

1. C₂H₂OH
2. CH₃COOH
3. CH₃CHO
4. HCHO

Answer: 1. C₂H₂OH

Question 23. On treatment with B₂H₆/H₂O₂, R-CH=CH₂ gives

1. RCOCH₃
2. RCHOH CH₂OH
3. RCH₂ CHO
4. RCH₂CH₂OH

Answer: 4. RCH₂CH₂OH

Question 24. Which of the following will give a yellow precipitate with I₂/NaOH?

1. CH₃COCH₂CH₃
2. CH₃COOCOCH₃
3. CH₃CONH₂
4. CH₃CH(OH)CH₂CH₃

Answer:  1 and 4 – CH₃COCH₂CH₃  and CH₃CH(OH)CH₂CH₃

Question 25. Phenol reacts with CHCl₃/aqueous NaOH. The electrophilic reagent which attacks the benzene nucleus is

1. CHCl₃
2. CHC1₂
3. COCI₂
4. CCl₂

Answer: 4. CCl₂

Question 26. Upon reacting with neutral FeCl₃, phenol gives a

1. Green colour
2. Violet colour
3. Red colour
4. Blue colour

Answer: 2. Violet colour

Question 27. The reaction of

Answer: 1 and 4

Question 28. The central oxygen atom of ether is

1. Sp-hybridised
2. Sp²-hybridised
3. Sp³d²-hybridised
4. sp-hybridised

Answer: 3.  Sp³d²-hybridised

Question 29. What is the order of dehydration of the following?

1. 1 < 2 < 3 <4
2. 2<3<4<1
3. 1< 3< 2<4
4. 1 < 4 < 2 = 3

Answer: 1. 1 < 2 < 3 <4

Question 30. How many isomeric acyclic alcohols and ethers are possible for C₄H₈O?

1. 7
2. 9
3. 5
4. 8

Answer: 4. 8

Question 31. Among the following reagents, phenol can be distinguished from ethyl alcohol by all except

1. NaOH
2. FeCl₃
3. Br₂/H₂O
4. Na

Answer: 4. Na

Question 32. The order of esterification of alcohol is

1. 3° > 2° > 1°
2. 1° > 2° >3°
3. 2° >3° 1°
4. None of these

Answer: 3. 2° >3° 1°

Aldehydes, Ketones and Carboxylic Acids

Aldehydes And Ketones

Aldehydes and ketones are compounds containing the carbonyl group (CO). When two alkyl groups are attached to the carbonyl group, the compound is a ketone. When two hydrogens, or one hydrogen and one alkyl group, are attached to the carbonyl group, the compound is an aldehyde.

The chemistry of the carbonyl group is extremely important. Aldehydes and ketones are reactive in nature. Many useful products such as dyes, resins, perfumes, plastics and cloths are made from them. Many useful compounds containing these functional groups can be obtained from plants.

For example, vanillin (from vanilla beans), salicylaldehyde (from meadow sweet) and cinnamaldehyde (from cinnamon). These are flavouring compounds. Vanillin is used for the vanilla flavour in ice creams. Salicylaldehyde has an odour like bitter almonds and is used in perfumery. Cinnamaldehyde is responsible for the flavour of cinnamon.

Nomenclature Of Aldehydes

Aldehydes are named using either of two different systems.

Trivial name

Simple aldehydes are commonly known by their trivial names or common names. According to this system, the name of an aldehyde is derived from the name of the corresponding carboxylic acid by dropping the suffix ic (oic) acid and adding in its place the suffix aldehyde.

In the common system of nomenclature, the position of an additional substituent is indicated by the Greek letters α, β, γ, etc., a being the carbon attached to the carbonyl group, β being the next carbon, and so on.

IUPAC name

In the IUPAC system, aldehydes are named by adding the suffix al to the name of the corresponding hydrocarbon, the ‘e’ of the hydrocarbon being omitted.

The substituents on the chain are prefixed in alphabetical order along with the numbers indicating their positions. These numbers are allocated by considering the aldehydic carbon to be the first carbon.

The IUPAC name of a simple aromatic aldehyde in which the aldehydic group is directly attached to the benzene ring is benzenecarbaldehyde. However, the common name benzaldehyde is also retained in IUPAC nomenclature. Other aromatic aldehydes are named as substituted benzaldehydes.

The common and IUPAC names of some aldehydes:

The following are examples of some more aldehydes and their IUPAC names:

A molecule with a double bond and a triple bond is called an enyne (ene + yne). A molecule with a double bond, triple bond and an aldehyde group is known as a enynal (ene + yne + al). The term is used as a suffix.

The numbering of carbons begins with the carbon of the aldehyde group. The substituents and the functional are located accordingly.

A molecule with two double bonds and an aldehyde group is known as a dienal (diene + al). The term is used as a suffix. Numbering of carbons begins with the carbon of the aldehyde group. The substituents and the functional groups are located accordingly.

If an unbranched chain is directly linked to more than two aldehydic groups, these aldehydes are named from the parent hydrocarbon by the substitutive use of a suffix, example,tricarbaldehyde. The suffix ‘al’ is not used. Numbering of carbons begins at the end nearest the functional group. The functional groups are located accordingly.

Nomenclature Of Ketones

Ketones too are named using either of two different systems.

Trivial names

Simple ketones may be named by using the names of the alkyl groups attached to the carbonyl group followed by the word ketone. The names of the alkyl groups are written alphabetically.

IUPAC names

In the IUPAC system ketones are named by adding the suffix ‘one’ to the name of the corresponding hydrocarbon and omitting the final ‘e’ of the hydrocarbon.

The position of the carbonyl group is given by a number which can be placed before the parent name as given below or immediately before the suffix (for example, pentane-2-one).

The common and IUPAC names of some ketones:

In the IUPAC system, the longest chain containing the carbonyl group is taken as the parent hydrocarbon and the positions of the carbonyl as well as any other substituent present in the molecule are indicated by numbers The longest chain containing the carbonyl group is numbered from the end that gives the carbonyl carbon the lowest number.

A molecule with a double bond and a ketone is called an enone (ene + one) and the term is used as a suffix. The numbering of carbons begins at the end nearest the functional group.

In cyclic ketone the carbonyl carbon is a

Example 1: Draw the structures of the following compounds.

1. β -Ethoxybutyraldehyde
2. 3-Methylcyclopentanecarbaldehyde
3. 3-Oxob utanal
4. Diisopropyl ketone
5. 4-Bromoacetophenone

Solution:

The allocation of Greek letters to the carbon atoms in the common system starts from the carbon next to the aldehyde group, whereas the numbers in the IUPAC system always begin with the carbon of the aldehyde group.

⇒ \(\stackrel{\beta}{\mathrm{C}}-\stackrel{\gamma}{\mathrm{C}}-\stackrel{\beta}{\mathrm{C}}-\stackrel{\alpha}{\mathrm{C}}-\mathrm{CHO}\) (Used In Common names)

⇒  \(\stackrel{5}{\mathrm{C}}-\stackrel{4}{\mathrm{C}}-\stackrel{3}{\mathrm{C}}-\stackrel{2}{\mathrm{C}}-\stackrel{1}{\mathrm{C}} \mathrm{HO}\)(Used In IUPAC names

Structures Of The Carbonyl Group Used In IUPAC Names

The carbon atom of the carbonyl group is sp2-hybridised and three of its electrons form three o bonds. The molecule is planar and the bond angles are close to 120°. The remaining p orbital of the carbon with one electron overlaps a p orbital of oxygen with one electron to form a bond between these atoms. The oxygen atom also has two lone pairs of electrons that occupy the remaining orbital.

The electrons in the bond of the carbonyl group are not equally shared. They are pulled more towards the more electronegative oxygen atom. As a result, the C-O bond is polarised in the direction C-O. Therefore, the electron-deficient carbonyl carbon is electrophilic (a Lewis acid) in nature and the electron-rich carbonyl oxygen is nucleophilic (Lewis base) in nature.

Due to bond polarity, carbonyl compounds have substantial dipole moments.

General Methods Of Preparation Of Aldehydes And Ketones

By the oxidation of alcohol

Aldehydes Primary alcohols yield aldehydes upon oxidation with pyridinium chlorochromate (PCC) in a CH₂ Cl₂ medium. Aqueous methods like Jones oxidation (Na₂Cr₂O₇ and dilute H₂SO₄ in acetone) are not useful for this purpose since the aldehyde that is formed is further oxidised to a carboxylic acid.

Ketones Secondary alcohols yield ketones upon oxidation with K₂Cr₂O₇/H₂SO₄ in an acetone medium.

Tertiary alcohols are stable to oxidation under these conditions.

Oppenauer oxidation

Oppenauer oxidation involves the oxidation of primary alcohols and secondary alcohols to aldehydes and ketones respectively in the presence of aluminium isopropoxide, Al[OCH(CH₃)₂]₃

By the dehydrogenation of alcohol

When the vapours of a primary alcohol are passed over hot copper at about 573 K, the alcohol is readily dehydrogenated to yield an aldehyde.

⇒ \(\underset{\text { (Primary alcohol) }}{\mathrm{R}-\mathrm{CH}_2 \mathrm{OH}} \underset{573 \mathrm{~K}}{\stackrel{\mathrm{Cu}}{\longrightarrow}} \underset{\text { (Aldehyde) }}{\mathrm{R}}-\mathrm{CHO}+\mathrm{H}_2\)

On dehydrogenation, secondary alcohols give ketones.

⇒ \(\underset{\text { (Secondary alcohol) }}{\mathrm{R}-\mathrm{CHOH}-\mathrm{R}^{\prime}} \underset{573 \mathrm{~K}}{\stackrel{\mathrm{Cu}}{\longrightarrow}} \underset{\text { (Ketone) }}{\mathrm{R}}-\mathrm{CO}-\mathrm{R}^{\prime}+\mathrm{H}_2\)

By the pyrolysis of calcium salts of carboxylic acids

When the calcium salts of carboxylic acids are heated to high temperatures, symmetrical ketones are obtained.

Formation of an aldehyde: On dry distillation, calcium formate gives formaldehyde.

On dry distillation, a mixture of calcium acetate and calcium formate yields acetaldehyde.

Formation of a ketone:  On dry distillation, the calcium salt of a carboxylic acid, other than formic acid, gives a ketone. For example, in dry distillation, calcium acetate gives acetone.

By the hydrolysis of gem-dihalides (1, 1-dihalides)

Formation of an aldehyde Boiling a gem-dihalide with aqueous NaOH gives a dihydroxy compound. Being unstable, this compound loses a water molecule readily to form an aldehyde.

Formation of a ketone If the halo groups are not present on the terminal carbon atom, i.e., the gem-dihalide is an internal dihalide, then a ketone is obtained.

By the hydration of alkynes

The hydration of alkynes with 20% H₂SO₄ in the presence of a mercuric salt (HgSO₄) gives aldehydes or ketones. Formation of an aldehyde On hydration with 20% H₂SO₄ in the presence of HgSO₄ at 353 K, acetylene gives an unstable enol, which soon isomerises to acetaldehyde.

Hydration of alkynes Mechanism:

Formation of ketones: On hydration with 20% H2SO4 in the presence of HgSO4 (catalyst) at 353 K, substituted alkynes give ketones.

By ozonolysis

Depending on the structure of an alkene, aldehydes and ketones are obtained by making the alkenes react with ozone and subsequent treatment with zinc dust and water.

The ozonide may also react with oxidising agents such as H₂O₂ to give carboxylic acids or with more powerful reducing agents such as NaBH, to give alcohols.

The ozonolysis of cyclohexene is particularly useful as it gives 1, 6-dicarbonyl compounds that are otherwise difficult to make. In the simplest case we get hexane-1, 6-dioic acid (adipic acid), a monomer used in the manufacture of nylon.

By the reduction of acid chlorides

Aldehydes Acid chlorides are reduced with hydrogen gas in the presence of palladised BaSO₄ or BaCO₃ (Rosenmund reduction) to aldehydes. Ketones are not prepared by this method.

⇒ \(\underset{\text { (Acid chloride) }}{\mathrm{R}-\mathrm{COCl}}+2 \mathrm{H} \stackrel{\mathrm{Pd} / \mathrm{BaSO}_4}{\longrightarrow} \underset{\text { (Aldehyde) }}{\mathrm{R}-\mathrm{CHO}+\mathrm{HCl}}\)

⇒ \(\underset{\text { Acetyl chloride }}{\mathrm{CH}_3-\mathrm{COCl}}+2 \mathrm{H} \stackrel{\mathrm{Pd} / \mathrm{BaSO}_4}{\longrightarrow} \underset{\text { Acetaldehyde }}{\mathrm{CH}_3 \cdot \mathrm{CHO}}+\mathrm{HCl}\)

The function of BaSO₄ is to poison the catalyst. This prevents the reduction of the aldehyde to an alcohol.

Ketones Acid chlorides react with dimethyl cadmium to yield ketones.

Grignard reagents, being more reactive than dimethyl cadmium, react with ketones to yield 3° alcohols. For this reason, Grignard reagents are not used in such reactions. Dimethyl cadmium does not react with ketones. Dimethyl cadmium can be prepared by making a Grignard reagent react with cadmium chloride.

⇒\(\underset{\text { Methylmagnesium bromide }}{2 \mathrm{CH}_3 \mathrm{MgBr}}+\mathrm{CdCl}_2 \rightarrow \underset{\text { Dimethylcadmium }}{\left(\mathrm{CH}_3\right)_2 \mathrm{Cd}}+2 \mathrm{MgBrCl}]\)

From alkyl cyanides

Aldehydes On reduction by stannous chloride and concentrated HCl, an alkyl cyanide (also called an alkyl nitrile) yields an imino chloride, which on hydrolysis with water yields an aldehyde. This reaction is known as the Stephen reaction.

Alkyl cyanides Mechanism:

Nitriles may also be selectively reduced by di-isobutylaluminium hydride (DIBAL-H) to imines, which upon hydrolysis give aldehydes.

DIBAL-H is sterically congested and therefore not very reactive. For this reason, it does not reduce the Di isobutyl aluminium hydride (DIBAL-H).

Ethylenic bond of unsaturated nitriles.

The reaction of an ester with exactly 1 equivalent of DIBAL-H at low temperature gives an aldehyde.

Ketones: On treatment with Grignard reagents, alkyl cyanides give ketones.

Physical Properties Of Aldehydes And Ketones

Formaldehyde is a gas while aldehydes or ketones containing up to 11 carbon atoms are colourless liquid Aldehydes and ketones containing more carbon atoms are solids.

Aldehydes and ketones are polar in nature. Their boiling points are higher than those of alkanes of similar molecular masses due to dipole-dipole interaction.

Because aldehydes and ketones are not associated with hydrogen bonds, their boiling points are lower than those of alcohols and carboxylic acids of comparable molecular weights.

The first few members of aliphatic aldehydes and ketones are soluble in water. For example, formaldehyde, acetaldehyde and acetone are soluble in water in all proportions. As the length of the alkyl group chain increases, the solubility of the compound decreases as in alcohols.

The solubility of lower aldehydes and ketones in water arises from the ability of the oxygen of the carbonyl group to form hydrogen bonds with water molecules.

All aldehydes and ketones are soluble to quite an extent in organic solvents like benzene and methyl alcohol. Formaldehyde and acetaldehyde have an unpleasant odour but higher aldehydes have a fruity smell.

Some of the ketones have a sweet smell. Many naturally occurring aldehydes and ketones are used as additives in perfumes and as flavouring agents.

Chemical Properties Of Aldehydes And Ketones

Aldehydes and ketones undergo similar chemical reactions because they contain the carbonyl functional group.

Nucleophilic addition reactions

The carbonyl group is represented by the two contributing structures

This imparts a substantial dipole moment to the carbonyl group, with the carbon bearing a partial positive harge and the oxygen bearing a partial negative charge.

The polar nature of the carbonyl group and the ability of the oxygen atom to accommodate the extra electron-air facilitates the attack of the nucleophile at the carbonyl carbon. The nucleophile normally adds to the carbony

Carbon from a direction approximately perpendicular to the plane of the sp2-hybridised orbitals of the carbonyl carbon. In this process, the hybridisation of the carbonyl carbon changes from sp’ to sp and a tetrahedral alkoxide anion intermediate is formed. The reaction is completed by the abstraction of a proton from the reaction medium to give the addition product.

Reactivity of aldehydes and ketones

Aldehydes are more reactive than ketones because of two factors.

Inductive effect The carbonyl carbon atom of a ketone carries two electron-donating groups, whereas that of an aldehyde has only one. Thus the ketone carbonyl carbon atom has less tendency to attract a nucleophile.

Steric effect Bulky groups adjacent to >C=O cause more steric strain in the addition product than in the parent carbonyl and reduce reactivity towards addition.

The order of reactivity of different carbonyl compounds towards nucleophilic addition is given below.

Example 2: Arrange the following carbonyl compounds in increasing order of their reactivity in nucleophilic addition reactions. Give reasons.

1. CH₃CHO, CH₃CH₂CHO, CH₃COCH₃, CH₃COCH₂CH₃

2.

Solution: 

1. The reactivity of aldehydes and ketones towards a nucleophile is influenced by the nature of the alkyl group attached to the carbonyl carbon in the following two ways.

• First, an electron-donating alkyl group reduces the positive charge of the carbonyl carbon and makes it less susceptible to nucleophilic attack.
• Secondly, the bulkier alkyl group attached to the carbonyl carbon presents greater steric hindrance than the smaller hydrogen atom to the approaching nucleophile.

From the above considerations, the increasing reactivity of the given compounds towards the nucleophile is as follows.

⇒ CH₃COCH₂CH₃<CH₃COCH₃<CH₃CH₂CHO<CH₃CHO

2. Similar influences are exerted by an aryl substituent as delocalised orbitals of the ring act as an electron source.

In the case of p-nitrobenzaldehyde, the electron-withdrawing nitro group at the p-position increases the positive character of the carbonyl carbon and thus facilitates the attack of nucleophiles.

In p-tolualdehyde, the methyl group at the p-position increases the electron density on the carbon of the carbonyl group by hyperconjugation as shown and makes it less reactive than benzaldehyde towards nucleophilic addition.

Acetophenone (a ketone) is less reactive than all the given aldehydes. The electron-donating methyl group and л-orbital of the benzene ring, acting as an electron source, make the carbonyl carbon electron-rich and less susceptible to nucleophilic attack. Further, the phenyl group and methyl group attached to the carbonyl carbon present greater steric hindrance to the approaching nucleophile.

On the basis of the above considerations, the order of increasing reactivity of the given compounds towards nucleophiles is as follows.

Ketones and aldehydes undergo very similar reactions. In this chapter, unless mentioned otherwise, each reaction discussed is equally applicable to both aldehydes and ketones and a generic structure is used for both.

Examples of nucleophilic addition reactions

Aldehydes and ketones undergo the following nucleophilic addition reactions.

Reaction with hydrocyanic acid (HCN) HCN adds to aldehydes and ketones to produce cyanohydrins.

The reaction is slow with pure HCN. However, in the presence of a base, CN (a stronger nucleophile) is generated, which readily adds to carbonyl compounds to yield the corresponding cyanohydrin.

⇒ \(\mathrm{HCN}+\mathrm{OH}^{-} \rightarrow: \overline{\mathrm{CN}}+\mathrm{H}_2 \mathrm{O}\)

Nucleophilic Mechanism:

The cyanide anion, the nucleophile, adds to the carbonyl carbon to yield an unstable intermediate oxygen anion, which, being a strong base, abstracts a proton from the solvent or HCN to give cyanohydrin.

Some plants produce cyanohydrins. The seeds of cherries, plums, peaches and apricots contain cyanohydrins. The odour and flavour of almonds is due to benzaldehyde and the cyanohydrin of benzaldehyde.

Addition of sodium bisulphite (NaHSO₄)

Aldehydes and ketones react with an aqueous, saturated solution of sodium bisulphite to yield a bisulphite product. This product is sparingly soluble in water and can be separated by filtration and decomposed by mineral acids to give back the carbonyl compound. The method is often used for separating a carbonyl compound from a noncarbonyl impurity.

Sodium bisulphite Mechanism:

Addition of Grignard reagents

Aldehydes and ketones react with Grignard reagents to produce alcohols. Formaldehyde yields primary (1°) alcohols, other aldehydes give secondary (2°) alcohols and all ketones give tertiary (3°) alcohols.

Grignard reagents Mechanism:

Addition of alcohol

In the presence of dry HCl gas, one mole of an aldehyde reacts with one mole of alcohol to give a hemiacetal (alkoxy alcohol), which again reacts with one mole of the alcohol to yield an acetal (gem-alkoxy compound).

Alcohol Mechanism:

Ketones do not react with monohydric alcohols in the presence of dry HCl but react with ethylene glycol (a dihydric alcohol) to form cyclic ketals.

In the presence of dry HCl gas, the oxygen atom of a carbonyl compound is bonded to H*, leaving a stabilised \(\left(>\mathrm{C}=\mathrm{O}+\mathrm{H}^{+} \rightleftharpoons>\mathrm{C}=\stackrel{+}{\mathrm{O}}-\mathrm{H} \leftrightarrow \stackrel{+}{\mathrm{C}}-\mathrm{OH}\right)\) arbonium ion, which can react with ethylene glycol (a nucleophile) to yield a cyclic ketal.

Reaction with ammonia derivative (NH₂-Y):

Several derivatives of ammonia such as

Can take part in addition reactions with aldehydes and ketones. The reaction is catalysed both by acids and alkalis. Under their influence, a molecule of water is eliminated, introducing a double bond between C and N. The products are crystalline, high-melting solids, very useful as derivatives for identification.

Ammonia derivative Mechanism:

Reaction with PCI₅

When aldehydes and ketones are treated with PCl₅, the oxygen atom of the carbonyl group is substituted by two chlorine atoms and gem-dihalides are formed.

Reduction

Reducing agents such as LiAlH₄, NaBH₄ and H₂/Ni reduce aldehydes to primary alcohols and ketones to secondary alcohols.

LiAlH₄ is a versatile reducing agent. It reduces not only aldehydes and ketones but carboxylic acids, esters and nitriles as well. Sodium borohydride is a weak and selective reducing agent and reduces aldehydes and ketones only, but not carboxylic acids. NaBH₄ is also unreactive towards C = C and C=C bonds.

If a molecule contains both an aldehyde and an ester, only the aldehyde will be reduced by NaBH₄.

Aldehydes and ketones may be reduced to hydrocarbons on treatment with Zn (Hg) and concentrated HCl. In this reaction, the >C=O group is converted into the >CH2 group. This reaction is known as Clemmensen reduction.

⇒ \(>\mathrm{C}=\mathrm{O}+4 \mathrm{H} \frac{\mathrm{Zn}-\mathrm{Hg}}{\mathrm{HCl}}>\mathrm{CH}_2+\mathrm{H}_2 \mathrm{O}\)

Aldehydes and ketones are also easily reduced to hydrocarbons in the presence of excess hydrazine and a strong base on heating. This reaction is known as Wolff-Kishner reduction.

Oxidation of aldehydes

Aldehydes are among the most readily oxidised classes of organic compounds. They are converted to carboxylic acid by numerous oxidising agents such as KMnO₄, K₂Cr₂O7 and HNO₃

Aldehydes are also oxidised by relatively weak oxidising agents such as Tollens reagent and Fehling’s solution.

Oxidation by Tollens reagen:

When an aldehyde is warmed with ammoniacal silver nitrate (Tollens reagent), the aldehyde is oxidised to carboxylic acid and the silver ion is reduced to free silver, which deposits in the form of a mirror on the inner wall of the test tube.

Ordinary mirrors are prepared in this way, using formaldehyde.

Tollens reagent is prepared by adding one drop of an aqueous solution of NaOH to a silver nitrate solution (10 mL) and dissolving the resultant precipitate in a minimum quantity of ammonium hydroxide solution.

⇒ \(\mathrm{AgNO}_3+\mathrm{NaOH}+2 \mathrm{NH}_4 \mathrm{OH} \rightarrow \underset{\text { Tollens reagent }}{\mathrm{Ag}\left(\stackrel{+}{\mathrm{NH}_3}\right)_2 \overline{\mathrm{O}} \mathrm{H}}+\mathrm{NaNO}_3+2 \mathrm{H}_2 \mathrm{O}\)

Oxidation by Fehling’s solution:

When heated with Fehling’s solution, an aldehyde is oxidised to a carboxylic acid and the Fehling’s solution is reduced to cuprous oxide (Cu₂O) as a brick-red precipitate.

Fehling’s solution is a deep blue solution prepared by mixing equal volumes of Fehling’s solution (1) and Fehling’s solution (2). Fehling’s solution (1) is an aqueous copper sulphate solution. Fehling’s solution (2) is an alkaline solution of sodium potassium tartrate (Rochelle salt).

When Fehling’s solution (1) is mixed with Fehling’s solution (2), a deep blue soluble complex is formed, which reacts with an aldehyde to form the sodium salt of a carboxylic acid and a red-brown precipitate of Cu₂O.

⇒ \(\mathrm{CuSO}_4+2 \mathrm{NaOH} \longrightarrow \mathrm{Cu}(\mathrm{OH})_2+\mathrm{Na}_2 \mathrm{SO}_4\)

Fehling’s solution can oxidise aliphatic aldehydes only, while Tollens reagent can oxidise aliphatic as well as aromatic aldehydes. These reagents have no effect on ketones.

The aldehyde group undergoes aerial oxidation. For example, crystals of benzoic acid grow inside a bottle filled with benzaldehyde in the presence of sunlight.

Oxidation by Benedict’s reagent:

Benedict’s reagent is an alkaline solution of copper sulphate, sodium carbonate and sodium citrate. On heating with Benedict’s reagent, aliphatic aldehydes yield a red-brown precipitate of Cu₂O

Using Benedict’s reagent we can detect the presence of sugar in urine.

Oxidation of ketones

The oxidation of ketones requires stronger oxidising agents such as permanganate and high temperatures. It involves the cleavage of a carbon-carbon bond adjacent to the carbonyl group, and different carboxylic acids are formed.

Oxidation of methyl ketones (haloform reaction) Aldehydes and ketones containing a keto methyl group are oxidised by sodium hypohalite (NaOX). Sodium salts of carboxylic acids containing one carbon less than the methyl ketone are formed. The methyl group forms a haloform.

For example, acetone is oxidised by I₂/NaOH to give iodoform. The three hydrogens in the methyl group are acidic and are readily displaced by the halogen to yield a triiodo compound which is cleaved under the influence of the alkali to yield iodoform and the corresponding carboxylic acid.

Iodoform is a pale yellow solid and its appearance indicates the presence of a methyl ketone.

Methyl ketones give the corresponding chloroform or bromoform with hypochlorite or hypobromite and so this reaction is known as a haloform reaction.

The hypohalite does not attack a double bond, if present in the molecule.

Compounds containing the methylcarbinol group also respond positively to the iodoform test.

Thus, even ethyl alcohol responds positively to the iodoform test.

Reactions due to α-hydrogen

A carbon atom located next to a carbonyl carbon is known as an a-carbon and hydrogens attached to an a-carbon are called a-hydrogens. These hydrogens are acidic due to the electron-withdrawing nature of the carbonyl group and resonance stabilisation of the conjugate base.

Aldol condensation:

Two molecules of an aldehyde or a ketone containing a-hydrogen undergo condensation in the presence of a dilute alkali to give a β-hydroxy aldehyde (aldol) or a β-hydroxy ketone (ketol). These reactions are called aldol condensation reactions.

Aldols (aldehyde-alcohols) can be dehydrated easily by heating to yield α, and β unsaturated aldehydes. For example, on heating, β-hydroxybutyraldehyde yields crotonaldehyde.

In the presence of Ba(OH)₂, two molecules of acetone condense to yield diacetonyl alcohol.

Aldol Condensation Mechanism:

Cross-aldol condensation:

An aldol condensation between two different carbonyl compounds, each containing a-hydrogen, gives a mixture of four products. This reaction is called a cross-aldol condensation.

It is generally difficult to separate a mixture of four products. A cross-aldol condensation yielding a pure product can, however, be obtained when one of the reactants has no α -hydrogen (for example, benzaldehyde, or maldehyde).

Other reactions

Cannizzaro reaction:

When an aldehyde that has no a-hydrogens is treated with a concentrated aqueous alkali, a disproportionation reaction occurs. One molecule of the aldehyde is reduced to a primary alcohol, and another molecule is oxidised to the corresponding carboxylic acid salt.

This reaction is known as the Cannizzaro reaction.

Cannizzaro reaction Mechanism:

Crossed Cannizzaro reaction: 

When an aldehyde that has no a-hydrogens is treated with formaldehyde and a strong base, it is the formaldehyde rather than the other aldehyde that is oxidised. Such a reaction is known as a crossed Cannizzaro reaction. For example,

Aromatic Aldehydes

Methods of preparation:

Aromatic aldehydes and ketones are prepared by the following methods.

Aromatic aldehydes

By the oxidation of toluene (Etard reaction), The partial oxidation of toluene by chromyl chloride (CrO₂ Cl₂) gives a chromium complex, which on hydrolysis yields benzaldehyde.

This reaction is known as the Etard reaction. If a strong oxidising agent is used, toluene is oxidised to benzoic acid.

Upon treatment with chromic oxide in acetic anhydride, toluene gives benzylidene diacetate. On hydrolysis with a dilute acid, Benzylidene diacetate yields benzaldehyde.

By the hydrolysis of benzal chloride:

On hydrolysis, benzal chloride yields benzaldehyde. Hydrolysis is done by using an aqueous NaOH solution. Benzal chloride is prepared by the chlorination of toluene in the presence of sunlight.

By the Gattermann-Koch synthesis:

Benzaldehyde is prepared by treating benzene or its derivative with CO+ HCl in the presence of anhydrous AlCl₃ and Cu₂Cl₂

Gattermann-Koch synthesis Mechanism:

Aromatic ketones

By the acylation of benzene:

Aromatic hydrocarbons react with acyl chloride in the presence of anhydrous AlCl₃ to yield aromatic ketones. For example, on treatment with acetyl chloride in the presence of anhydrous AlCl₃ benzene or substituted benzene gives acetophenone.

Acylation of benzene Mechanism:

Chemical Reactions

Most of the chemical reactions of benzaldehyde are similar to those of aliphatic aldehydes. We will now discuss some reactions of benzaldehyde which are different from those of aliphatic aldehydes.

Perkin reaction:

On being heated with acetic anhydride in the presence of sodium acetate, benzaldehyde gives cinnamic acid (a, B- unsaturated acid).

⇒ \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{CHO}+\left(\mathrm{CH}_3 \mathrm{CO}\right)_2 \mathrm{O} \stackrel{\mathrm{CH}_3 \mathrm{COONa}}{\longrightarrow} \mathrm{C}_6 \mathrm{H}_5 \mathrm{CH}=\mathrm{CHCOOH}+\mathrm{CH}_3 \mathrm{COOH}\)

This reaction is known as the Perkin reaction.

Perkin reaction Mechanism:

Benzoin condensation

Benzaldehyde and most other aromatic aldehydes undergo a self-condensation, known as benzoin condensation, when treated with potassium cyanide in an alcoholic solution. The product formed from benzaldehyde is called benzoin.

Benzoin condensation Mechanism

Claisen-Schmidt reaction

Benzaldehyde undergoes condensation with aldehydes and ketones in the presence of a dilute alkali at room temperature to yield unsaturated carbonyl compounds.

Reaction with aniline

On being heated with aniline, benzaldehyde yields benzylidene aniline (Schiff base).

Electrophilic substitution reactions

The benzene ring of aromatic aldehydes and ketones undergoes nitration, sulphonation and halogenation to yield the corresponding meta-substituted product.

Example 3: Complete each reaction below by supplying the missing starting material, reagent(s) or product. 

1. \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{CH}_2 \mathrm{OH} \rightarrow \mathrm{C}_6 \mathrm{H}_5 \mathrm{CHO}\)

2. \(\mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CN} \rightarrow \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CHO}\)

3. \(\mathrm{CH}_3 \mathrm{CH}=\mathrm{CHCH}_3 \rightarrow \mathrm{CH}_3 \mathrm{CHO}\)

Solution: 

1.  \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{CH}_2 \mathrm{OH} \stackrel{\mathrm{PCC}}{\longrightarrow} \mathrm{C}_6 \mathrm{H}_5 \mathrm{CHO}\)

A primary alcohol is oxidised to an aldehyde by PCC. (i) CH,CH,CN DIBAL-HCH,CH,CHO

2. \(\mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CN} \stackrel{\text { DIBAL-H }}{\longrightarrow} \mathrm{CH}_3 \mathrm{CH}_2 \mathrm{CHO}\)

A nitrile is converted to an aldehyde by DIBAL-H.

This is an Etard reaction. The partial oxidation of p-fluorotoluene by chromyl chloride (CrO₂Cl₂) gives a chromium complex, which on hydrolysis yields p-fluorobenzaldehyde.

5.  \(\mathrm{CH}_2=\mathrm{CH}-\mathrm{CH}_2 \mathrm{OH} \stackrel{\mathrm{PCC}}{\longrightarrow} \mathrm{CH}_2=\mathrm{CH}-\mathrm{CHO}\)

A primary alcohol is oxidised to aldehyde by PCC. The double bond is not affected by oxidation with PCC.

NaBH₄ is a weak reducing agent. It only reduces the ketonic group to a secondary alcoholic group. Double bonds are not affected by NaBH₄. H₂ Pt (cat.)

In catalytic hydrogenation, only ethylenic double bonds are reduced. The ketonic group remains unaffected.

LiAlH is a versatile reducing agent. It reduces the aldehydic group to a primary alcoholic group.

11. \(2 \mathrm{CH}_3 \mathrm{COCl} \stackrel{\left(\mathrm{CH}_3\right)_2 \mathrm{Cd}}{\longrightarrow} 2 \mathrm{CH}_3 \mathrm{COCH}_3+\mathrm{CdCl}_2\)

Acid chlorides react with dimethyl cadmium to give ketones.

This is a Friedel-Crafts acylation reaction.

Mechanism:

Uses Of Aldehydes And Ketones

1. Formalin (40% aqueous solution of formaldehyde) is used to preserve biological specimens.
2. Formaldehyde is used to prepare the most important plastic bakelite (a phenol-formaldehyde plastic).
3. Acetaldehyde is used for manufacturing organic compounds such as acetic acid, ethyl acetate, acetic anhydride and 1-butanol.
4. Benzaldehyde is used in perfumery and the dye industry.
5. Butyraldehyde, vanillin and camphor are used as flavouring agents in the perfume industry.

Carboxylic Acids

Organic compounds which contain a carboxyl group  are termed carboxylic acids. The group is so named because it can be considered as a combination of the carbonyl and hydroxyl groups.

Carboxylic acids may be aliphatic or aromatic. Aliphatic carboxylic acids are compounds in which the carbon of the carboxyl group is attached to an alkyl group and aromatic carboxylic acids are those in which the carbon of the carboxyl group is attached to an aryl group.

The unbranched long-chain monocarboxylic acids (C₁₃ -C₁₈) (monocarboxylic acids are compounds in which only one -COOH group is present) are commonly called fatty acids because many of them are obtained by the hydrolysis of animal fats or vegetable oils. Oils and fats are in fact esters of glycerol and fatty acids. Important fatty acids are stearic acid (C₁₇H₃₃COOH), palmitic acid (C₁₅ H₃₁ COOH) and oleic acid (C₁₇H₃₃COOH).

Formic acid is produced by ants and nettles. The sting of ants and nettles irritates the skin. Acetic acid is responsible for the sour taste of vinegar.

Nomenclature

Two systems of nomenclature are currently in use for carboxylic acids.

Trivial name

Simple carboxylic acids are known by their trivial names or common names derived from their natural sources, e.g., formic acid (Latin: formica, ant), acetic acid (Latin: acetum, vinegar), butyric acid (Latin: butyrum, butter). In substituted acids, the positions of the substituents are indicated by the Greek letters a, ẞ, 7, 8 and so on. The carbon atom next to the carboxyl group is a. For example,

IUPAC name

The IUPAC name of a monocarboxylic acid is derived from the name of the corresponding alkane by dropping the last ‘e’ of the alkane and adding the suffix ‘oic acid’. Positions of substituents on the chain are worked out by considering the carboxylic carbon to be C(1).

Carboxylic acids containing more than one carboxylic acid group are named by retaining the ending’-e’ of the alkane and the number of carboxylic acids are indicated by adding the prefix di, tri, etc., to the term ‘oic acid’. The positions of carboxylic acid groups are located by numbers.

The common and IUPAC names of some carboxylic acids

The following are some formulae and IUPAC names of carboxylic acids

[Note: If an unbranched chain is directly linked to more than two carboxyl groups, these carboxylic acids are named from the parent hydrocarbon by the substitutive used of a suffix such as ‘tricarboxylic acid’, etc., in place of the suffix ‘oic acid’.]

Alicyclic carboxylic acids are also named by adding the suffix ‘carboxylic acid’ to the name of a parent hydrocarbon. For example,

Methods Of Preparation

By the oxidation of primary alcohols or aldehydes

The oxidation of primary alcohols yields a carboxylic acid. The oxidising agent most often used is potassium permanganate in an acidic or alkaline medium, or potassium dichromate or chromium trioxide in an acid medium.

⇒ \(\mathrm{RCH}_2 \mathrm{OH} \underset{\text { 2. } \mathrm{H}_3 \mathrm{O}^{+}}{\stackrel{\text { alkaline } \mathrm{KMnO}_4}{\longrightarrow}} \mathrm{RCOOH}\)

⇒ \(\mathrm{RCH}_2 \mathrm{OH} \stackrel{\mathrm{K}_2 \mathrm{Cr}_2 \mathrm{O}_7 / \mathrm{H}_2 \mathrm{SO}_4}{\longrightarrow} \mathrm{RCOOH}\)

The initial product in the oxidation of a primary alcohol is the corresponding aldehyde. However, the aldehyde undergoes oxidation more rapidly than the primary alcohol. So it is normally not shown in the equation. Both aliphatic and aromatic aldehydes are readily oxidised to carboxylic acids even by mild oxidising agents like Tollens reagent. But usually, acid dichromate or permanganate solutions are used for oxidation.

By the oxidation of alkylbenzenes (Side-chain oxidation)

Aromatic compounds with alkyl side chains are oxidised with alkaline KMnO₄, acidified K₂Cr₂O₇ or chromic acid to carboxylic acids. For example, toluene, propylbenzene and isopropylbenzene are oxidised to benzoic acid on oxidation with alkaline KMnO₄. As t-butylbenzene does not possess hydrogen on the benzyl carbon, it is not oxidised to benzoic acid.

By the hydrolysis of nitriles and amides

Aliphatic and aromatic nitriles give carboxylic acids on hydrolysis upon boiling with acids or alkalis.

Nitriles and Amides Mechanism:

In order to obtain amides rather than carboxylic acids, mild reaction conditions are used. (Then the reaction stops at the amide stage.)

Grignard reagents: Grignard reagents (RMgX) react with carbon dioxide (dry ice is a convenient source of CO₂) to yield salts of carboxylic acids. Treatment of the salt with a mineral acid liberates the carboxylic acid.]

Grignard reagents Mechanism :

By the hydrolysis of esters, amides, acid halides and acid anhydrides

On hydrolysis, esters, amides, acyl halides and acid anhydrides give carboxylic acids.

(Y = OR,X,NH₂,OCOR)

Hydrolysis of esters Esters undergo hydrolysis by refluxing with dilute HCl or dilute alkali to yield carboxylic acids. Acidic hydrolysis gives carboxylic acid directly but alkaline hydrolysis with dilute NaOH gives the sodium salt of a carboxylic acid, which on acidification yields carboxylic acid.

With acid:

⇒ \(\mathrm{CH}_3-\mathrm{COOC}_2 \mathrm{H}_5+\mathrm{H}_2 \mathrm{O} \stackrel{\mathrm{H}^{+}}{\rightleftharpoons} \mathrm{CH}_3 \mathrm{COOH}+\mathrm{C}_2 \mathrm{H}_5 \mathrm{OH}\)

With alkali:

⇒ \(\mathrm{CH}_3 \mathrm{COOC}_2 \mathrm{H}_5+\mathrm{H}_2 \mathrm{O} \stackrel{\mathrm{OH}^{-}}{\rightleftharpoons} \mathrm{CH}_3 \mathrm{COOH}+\mathrm{C}_2 \mathrm{H}_5 \mathrm{OH}\)

⇒ \(\mathrm{CH}_3 \mathrm{COOH}+\mathrm{OH}^{-} \rightleftharpoons \mathrm{CH}_3 \mathrm{COO}^{-}+\mathrm{H}_2 \mathrm{O}\)

Mechanism of alkaline hydrolysis of esters:

Hydrolysis of amides: On Hydrolosis with acid or alkaline amides yield carboxylic acids

 Alkaline hydrolysis of amides Mechanism:

Hydrolysis of acid halides and acid anhydrides:

Acid halides and Acid anhydrides Mechanism:  

Physical Properties Of Monocarboxylic Acids

Lower carboxylic acids (with up to nine carbon atoms) are liquids with disagreeable odours. Higher members are waxlike solids. They are less volatile and almost odourless. Formic acid and acetic acid are present in traces in the secretions of our skin.

The ability of a dog to differentiate one person from another depends upon its highly developed sense of smell. Since the metabolic processes of different persons are different, the composition of lower carboxylic acids secreted by the skin is different in case of different people and a dog is able to distinguish one person from another.

The boiling points of carboxylic acids are higher than those of other classes of compounds of comparable molecular weight. For example, acetic acid (molecular weight 60) boils at 393 K, but propanol (molecular weight 60) boils at 370 K, and ethyl chloride (molecular weight 64) boils at only 286 K.

The increase in boiling point is attributed to the hydrogen bonding between the carboxylic acid molecules. More heat is required to break hydrogen bonds in the dimeric structure of carboxylic acids.

Example 4: Arrange te following compounds in increasing order of their boiling points give reasons

C₂H₅–O–C₂H₅, CH₃CH₂COOH, CH₃CH₂CH₂CH₂OH, CH₃CH₂CH₂CHO, CH₃CH₂CH₂ CH₂CH₃.

Solution:  

The boiling points of carboxylic acids are higher than those of other classes of compounds of comparable molecular mass. For example, propanoic acid (molecular mass = 74) boils at 414 K, 1-butanol (molecular mass = 74) boils at 391 K, butanal (molecular mass = 72) boils at 347.7 K, ethoxyethane (molecular mass = 74) boils at 318 K and n-pentane (molecular mass = 72) boils at 319 K. The high boiling point of propanoic (propionic) acid is attributed to the dimeric structure due to hydrogen bonding.

Propionic acid forms even stronger hydrogen bonds than does 1-butanol. The O-H bond of propionic acid is more strongly polarised as O-H due to the adjacent electron-attracting carbonyl group and the hydrogen bridge may be bonded to the more negatively charged carbonyl group rather than to the oxygen of another O-H bond of the carboxylic acid group.

The carbonyl group of butanal  is more polar in nature than the C-O-C group in ethoxyethane (C₂H₅-O-C₂H₅). The dipole-dipole attraction of the molecules of butanal is stronger than in ethoxyethane. Therefore, the boiling point of butanal is higher than that of ethoxyethane.

On the other hand, butanal does not form hydrogen bonds, and its boiling point is lower than those of 1-butanol and propanoic acid. n-pentane is nonpolar in nature, the only attractive forces among the molecules of n-pentane being the weak van der Waals attractive forces.

Therefore, the increasing order of boiling points of the given compounds is as follows.
CH₃CH₂CH₂CH₂CH₃ <CH₃CH₂OCH₂CH₃<CH₃CH₂CH₂CHO <CH₃CH₂CH₂CH₂OH
<CH₃CH₂COOH

Lower members of the carboxylic acids are completely soluble in water. This is because of the ability of the carboxyl group to form hydrogen bonds with water molecules. 

Higher fatty acids are insoluble in water due to the increased hydrophobic nature of long-chain alkyl groups.

Structure Of Carboxylic Acids

A carboxylic acid may be thought of as a resonance hybrid of the following two structures.

This resonance interaction has two important consequences.

1. The O-H bond is weakened by the electron-withdrawing effect of the carbonyl group so that typical carboxylic acids (pK_a =4±1) are much more acidic than alcohol (pK_a 17). The conjugate base of a carboxylic acid is also stabilised by resonance. The negative charge is shared equally by both oxygens, making them completely equivalent.

2. The electrophilicity of the carbonyl group is reduced by the electron-donating effect of the O-H group. Therefore, carboxyl carbon is less reactive towards nucleophiles than the carbonyl group of aldehydes and ketones.

Due to the diminished electron-withdrawing capacity of the carbonyl group in carboxylic acids (and their derivatives), α -hydrogens in such compounds are less acidic than those in ketones and aldehydes.

Strength Of Carboxylic Acids

The strength of a Bronsted acid is usually expressed in terms of its pK_a value. The lower the pKa value, the stronger is the acid. The pK_a values for a large number of carboxylic acids are known.

Table 12.5 pKa values for selected carboxylic acids (R-COOH)

From the table, it is evident that substituted acids (CICH₂-COOH, CI₂ CH-COOH and CI₂ C-COOH) as well as formic acid are stronger than acetic acid.

It is reasonable to expect that electron-donating substituents [Example, CH₃-C₂H₃-,(CH₃)₂, CH-,(CH₃)₃C-1 should be acid weakening while electron-withdrawing substituents (-Cl₂ -NO₂, CN₂ etc.) should be acid strengthening. The closer the substituent group is to the carboxyl group, the greater the effect it will have.

Further, if the number of electronegative halogens on the a-carbon is increased from one to three, the pK value reaches that of a strong mineral acid. The three halogens of trichloroacetic acid exert strong as shown. Due to this, the hydrogen of the -COOH group can readily leave as a proton.

When groups such as C₆H₅, and vinyl (CH₂=CH-) are attached to the carboxyl group then the acid strength should decrease due to resonance, as shown below.

But, in fact, the acid strength increases because an sp² carbon has greater effective electronegativity than an sp carbon.

In the presence of electron-attracting groups (NO₂, Cl, SO₃ H), the acid strength of aromatic carboxylic acids increases and in the presence of electron-donating groups (CH₃, OH, OCH₃, etc.), the acid strength decreases.

Example: Among the following pairs of acids, which is stronger? Give reasons

1. CH₃COOH or CICH₂COOH

2. FCH₂COOH or CICH₂COOH

Solution:

Generally, the acidity of a compound is increased by electron-attracting substituents whi electron-donating substituents decrease acid strength. Chloroacetic acid is more acidic tha acetic acid. The higher acidity of chloroacetic acid is attributed to inductive effect. The chlori atom on chloroacetic acid assists in loosening the O-H bond and making the proton eas removable by pulling the electron towards itself due to its high electronegativity.

The electron-donating methyl group in acetic acid decreases the acid strength.

The larger the electron-withdrawing inductive effect, the greater is the acidity. As a result, fluoroacetic acid is stronger than chloroacetic acid-fluorine is considerably more electronegative than chlorine.

Inductive effect decreases rapidly with distance. The carboxylic acid in which the electron-attracting nitro group is closer to the carboxyl group is stronger because it can pull electrons more effectively. Therefore, 3-nitrobutanoic acid is stronger than 4-nitrobutanoic acid.

The electronegative CCl₃– group attracts electrons from the benzene ring, resulting in a positive charge on the carbon atom adjacent to the carboxylic group.

This in turn induces a positive charge on the carboxyl carbon. This results in the release of a proton to yield the carboxylate anion. The carboxylate anion is readily stabilised through resonance and increases the acid strength.

The effect in p-methylbenzoic acid is opposite to that in 4-trichloromethylbenzoic acid. The methyl group is able to donate electrons to the benzene ring through hyperconjugation and built up a negative charge on the carboxyl carbon. This additional charge tends to hold the proton and thus decreases the acid character.

Chemical Properties Carboxylic Acids

The chemical reactions of the carboxylic group involve the following.

1. Cleavage of the O-H bond,
2. Cleavage of the C-OH bond,
3. The COOH group, and
4. Substitution reactions in the hydrocarbon part.

Reactions involving cleavage of the O-H bond

Reactions with metals and alkali Like alcohols, carboxylic acids also evolve hydrogen with sodium metal and like phenols, carboxylic acids react even with weak bases, such as sodium carbonate and sodium bicarbonate, to evolve carbon dioxide.

2CH₃COOH + 2Na→2CH₃COONa+ H₂

CH₃COOH + NaOH → CH₃COONa +H₂O

CH₃COOH + NaHCO₃-CH₃COONa +H₂O+CO₂↑

Note that the evolution of CO₂ is from NaHCO₃ and not from the carbxylic acid. This reaction is used to detect the -COOH group in an unknown organic compound. Carboxylic acids evolve CO₂ with effervescence.

Carboxylic acids are only partially ionised in an aqueous solution and thus display weak acidic properties. A convenient way to measure the acidity of an acid is in terms of its ionisation constant (K_a) and PK_avalues. For acetic acid, the expression for K_a is obtained as follows.

⇒ \(\mathrm{CH}_3 \mathrm{COOH}+\mathrm{H}_2 \mathrm{O} \rightleftharpoons \mathrm{CH}_3 \mathrm{COO}^{-}+\mathrm{H}_3 \stackrel{+}{\mathrm{O}}\)

For the above reaction

⇒ \(K_{\mathrm{a}}=\frac{\left[\mathrm{CH}_3 \mathrm{COO}^{-}\right]\left[\mathrm{H}_3 \stackrel{+}{\mathrm{O}}\right]}{\left[\mathrm{CH}_3 \mathrm{COOH}\right]}\)

The concentration term for water is neglected since it is not affected to any appreciable extent by the ionisation of the acid. A higher value for K_a implies a strong acid.

The strength of an acid is also indicated by its pK, value.

pK_a = -log K_a

Thus, for acetic acid, whose K_a is 1.8 × 10-5, the pK_a can be calculated.

PK-log (1.8 × 10^-5)=

-0.3+5=4.7.

A smaller value of pK_a implies a stronger acid (excellent proton donor). For hydrochloric acid, the pK, value is -7.0. The corresponding values for trifluoroacetic acid, benzoic acid and acetic acid are 0.23, 4.19 and 4.7 respectively.

Stronger acids have pK, values < 1, moderately strong acids have pK, values between 1 and 5, weak acids have pK, values between 5 and 15, and extremely weak acids have pK, values > 15.

Reactions involving cleavage of the C-OH bond

Esterification Carboxylic acids react readily with alcohols or phenol in the presence of catalytic amounts of mineral acids (concentrated H₂SO₄) to yield esters. The process is called esterification. The conversion of a carboxylic acid into an ester involves nucleophilic substitution at the carbonyl (acyl) carbon.

First of all, the carbonyl oxygen of the -COOH group is protonated, which fascilitates the nucleophilic addition of the alcohol (the alcohol serving as the nucleophile) to the carbonyl group, yielding a tetrahedral intermediate.

Proton transfer of the intermediate converts the acid’s OH group to the protonated form which, being a good leaving group, departs as a water molecule. The protonated ester so formed finally loses a proton to give an ester.

C-OH bond Mechanism:

The reaction has several notable characteristics.

• It is reversible. Completion of the reaction requires either water to be removed by azeotropic distillation o an excess of one of the reagents (usually alcohol) to be used.
• The alcohol’s oxygen is retained in the ester, indicating that the R-O bond does not break during the reaction.
• The reaction requires catalysis by strong acids.

Reactions with PCI₅, PCI₃ and SOCI₂ The reaction of a carboxylic acid with PCl₅, PCI₃ or

SOCI₂ yields an acid chloride.

⇒ RCOOH + PCI₅→ RCOC1 + POCl₃ + HCl

⇒ 3RCOOH+ PCl₃, 3RCOCI+ H₃PO₃

⇒ RCOOH + SOCI₂→ RCOCI+ HCI ↑+ SO₂ ↑

With thionyl chloride, the by-products are both gases. With the phosphorus halide, the by-products are either nonvolatile phosphorus acid or the volatile liquid phosphorus oxychloride (boiling point 378 K). The latter may be difficult to separate from the acid chloride if the boiling points of the two are similar. Therefore, thionyl chloride is preferred for the preparation of acid chlorides.

Reaction with ammonia:

Carboxylic acids react with ammonia to yield ammonium salts, which give amides on being heated. For example,

Formation of anhydrides:

On being heated with concentrated H₂SO₄ or P₂O₅, a carboxylic acid gives an acid anhydride.

Carboxylic acids may be converted to their anhydrides by making their sodium salts react with the corresponding acid chloride.

⇒ RCOONa + RCOC1→ R–COO–COR+NaCl

Mixed anhydrides can also be prepared by this process.

⇒ RCOONa + R’COC1→ RCO—0—COR’ + NaCl

Reactions involving the carboxyl group

Reduction:

Carboxylic acids are conveniently reduced to primary alcohols upon reaction with lithium aluminium hydride in ether or with diborane, which reduces esters, nitro and halo groups with difficulty. Sodium borohydride is a weak reducing agent and does not reduce the carboxyl group.

Decarboxylation: on dry distillation with soda lime, the sodium salt of a carboxylic acid gives an alkane.

The decarboxylation (removal of CO₂) of a carboxylic acid takes place through the carboxylate anion from which the group ^–CH₃ departs along with its bonding electron pair. The carbanion (carbon carrying a negative charge) reacts with a proton to give the alkane.

Decarboxylation Mechanism:

Kolbe’s electrolytic method: In this method, an aqueous solution of a sodium salt of carboxylic acid is subjected to electrolysis to yield an alkane.

⇒ 2CH₃COONa+ 2H₂O→C₂H6 +2CO₂ + 2NaOH + H₂ at anode at cathode

In another reaction, dry distillation with calcium formate, the calcium salt of a carboxylic acid gives an aldehyde. For example, a mixture of calcium acetate and calcium formate yields acetaldehyde on dry distillation.

On dry distillation, the calcium salt of a carboxylic acid gives a ketone. For example, calcium acetate, on dry distillation, yields acetone.

Hunsdiecker reaction:

Carboxylic acids form silver salts when their ammoniacal solutions are treated with silver nitrate. On being refluxed with Br₂, the salt forms an alkyl bromide. This is known as the Hunsdiecker reaction.

⇒  \(\underset{\text { Silver carboxylate }}{\mathrm{RCOOAg}}+\mathrm{Br}_2 \underset{\Delta}{\stackrel{\mathrm{CCl}_4}{\longrightarrow}} \underset{\text { Alkyl bromide }}{\mathrm{R}-\mathrm{Br}}+\mathrm{CO}_2+\mathrm{AgBr}\)

Substitution reactions in the hydrocarbon part

Halogenation:  When treated with chlorine or bromine in the presence of red phosphorus, aliphatic carboxylic acids containing a-hydrogen form a-halogen acids.

Similarly,

This reaction is called the Hell-Volhard-Zelinsky reaction or HVZ reaction.

Halogenation Mechanism:

Reducing properties of formic acid

Formic acid shows reducing properties in the following reactions.

Reaction with Tollens reagent:  On gently warming with Tollens reagent, formic acid gives a grey precipitate of metallic silver.

⇒ HCOOH + 2Ag(NH₃)₂(Tollens reagent)OH → Ag + CO₃ +H₃O+4NH₃

Reaction with Fehling’s reagent: Upon being heated with Fehling’s reagent, formic acid gives a brick-red precipitate of Cu₂O.)

Reaction with mercuric chloride: Formic acid reduces mercuric chloride to mercuric chloride (Hg₂Cl₂) as a white precipitate. Mercurous chloride is further reduced to mercury as a grey precipitate.

⇒ HCOOH+2HgCl₂Hg₂Cl₂ + CO₂ + 2HCl

⇒ HCOOH+Hg₂Cl₂→ 2Hg(grey ppt.) +CO₂+2HCl

Electrophilic substitution reactions of benzoic acid

Nitration:

Aromatic carboxylic acids undergo electrophilic substitution reactions. In benzoic acid, the -COOH group deactivates the benzene ring and is meta-directing. On nitration with concentrated HNO₃ and concentrated H₂SO₄, benzoic acid gives m-nitrobenzoic acid.

Benzoic acid does not undergo Friedel-Crafts reaction (alkylation or acylation) because this reaction is not possible with a deactivated aromatic nucleus and the catalyst anhydrous AICI₃ (Lewis acid) gets bonded with the COOH group as shown below.

Halogenation:

In the presence of ferric bromide, which acts as a catalyst, benzoic acid reacts with bromine to form m-bromobenzoic acid.

Carboxylic Acids Uses 

• Formic acid is used in the rubber, cloth, dye and leather industries.
• Acetic acid is used as a solvent and in the preparation of vinegar.
• .Higher fatty acids are used in the manufacture of soaps and detergents.

Aldehydes, Ketones and Carboxylic Acids Multiple-Choice Questions

Question 1. The functional group of an aldehyde is

Answer: 2.

Question 2. The general formula of aldehydes and ketones is

1. C_n H_2n-2O
2. C_n H_2nO
3. C_nH_2n+1O
4. C_nH_2nO₂

Answer: 2. C_n H_2nO

Question 3. The IUPAC name of acetone is

1. Methanal
2. Ethanal
3. Propanone
4. Ethanone

Answer:  3. Propanone

Question 4. Which of the following is used to distinguish between an aldehyde and a ketone?

1. Concentrated H₂SO₄
2. Hydrazine
3. Tollens reagent
4. Nitrous acid

Answer: 3. Tollens reagent

Question 5. On being heated with NaOH solution, formaldehyde gives

1. Formic acid
2. Acetonw
3. Methyl alcohol
4. Ethyl formate

Answer: 3. Methyl alcohol

Question 6. Which of the following is formed when a mixture of calcium acetate and calcium formate is dry distilled?

1. Methanol
2. Ethanol
3. Ethanal
4. Acetic acid

Answer:  4. Acetic acid

Question 7. Which of the following is involved in the Cannizzaro reaction?

1. CH₃CHO
2. HCHO
3. HCOOH
4. CH₃COCH₃

Answer: 2. HCHO

Question 8. On dry distillation, calcium acetate gives

1. Ethyl acetate
2. Calcium formate
3. Acetone
4. Acetaldehyde

Answer: 3. Acetone

Question 9. Which of the following reagents reacts with aldehydes as well as ketones?

1. Tollens reagent
2. Fehling’s solution
3. Schiff base
4. Grignard reagent

Answer: 4. Grignard reagent

Question 10. Which of the following can be used to distinguish between aldehydes and ketones?

1. Fehling’s solution
2. H₂SO₄
3. NaHSO₃
4. NH₃

Answer: 1. Fehling’s solution

Question 11. Which of the following responds positively to the iodoform test?

1. C₂H₂OH
2. CH₃OH
3. CH₃CHO
4. C₂H₄c

Answer: 1 and 3 Or C₂H₂OH and CH₃CHO

Question 12. Which of the following is oxidised to acetone?

1. CH₃ CHO
2. C₂H₅OH
3. CH₃OH
4. CH₃-CHOH-CH₃

Answer: 3. CH₃OH

Question 13. On reacting with chlorine, acetaldehyde gives

1. Acetyl chloride
2. Chloral
3. Dichloroacetic acid
4. None of these

Answer:  2. Chloral

Question 14. On being heated with ammoniacal silver nitrate, acetaldehyde gives

1. Acetone
2. Silver acetate
3. A silver mirror
4. Formaldehyde

Answer: 3. A silver mirror

Question 15. In the following reaction, what is the appropriate reagent?

1. NH-NH₂, KOH
2. Zn/Hg,
3. H₃/Ni
4. NaBH₄

Answer: 1. NH-NH₂, KOH

Question 16. What is the correct order of reactivity of C₆H₅ MgBr with the following?

1. 1 > 2> 3
2. 3 >2 >1
3. 2>3>1
4. 1 >2 >3

Answer: 3. 2>3>1

Question 17. Which of the following reagents is used to separate acetaldehyde from acetophenone?

1. NaHSO₃
2. C₆H₅NHNH₃
3. NH₂OH
4. NaOH/I₂

Answer: 4. NaOH/I₂

Question 18. On treatment with 1% HgSO₄ and 20% H₂SO₄, but-1-yne gives

1. CH₃CH₂COCH₃
2. CH₃CH₂CH₂CHO
3. CH₃CH₂CHO and HCHO
4. CH₃CH₂CHOO and HCOOH

Answer: 1.

Question 19. The boiling points of the compounds

1. CH₃CH₂CH₂CHO
2. CH₃CH₂COOH and HCOOH
3. CH₃CH₂CH₂OH
4. CH₃COOH I

Answer: 3. CH₃CH₂CH₂OH

Question 20. The formation of cyanohydrin from CH₃COCH₃ is an example of

1. Electrophilic substitution
2. Nucleophilic substitution
3. Nucleophilic addition
4. Electrophilic addition

Answer: 3. Nucleophilic addition

Question 21. Which of the following products is obtained when CH₃MgBr reacts with formaldehyde?

1. C₂H₂OH
2. CH₃COOH
3. HCHO
4. CH₃CHO

Answer: 1. C₂H₂OH

Question 22. In which of the following reactions does an aromatic aldehyde react with acetic anhydride in the presence of sodium acetate to give an unsaturated aromatic acid?

1. Friedel-Crafts reaction
2. Wurtz reaction
3. Perkin reaction
4. None of these

Answer: 2. Wurtz reaction

Question 23. Which of the following does not respond positively to the iodoform test?

1. 2-pentanone
2. 3-pentanone
3. Ethanal
4. Ethonol

Answer: 2. 3-pentanone

Question 24. Which of the following is Tollens reagent?

1. [Ag(NH₃)₂]+ ion
2. Cu(OH)₂
3. CuO
4. Ag₂O

Answer: 1. [Ag(NH₃)₂]+ ion

Question 25. Which of the following is used to distinguish between aliphatic and aromatic aldehydes?

1. Tollens reagent
2. Benedict’s reagent
3. Schiff base
4. Iodoform reaction

Answer: 4. Iodoform reaction

Question 26. Which of the following reactions does benzaldehyde not undergo?

1. Aldol condensation
2. Benzoin condensation
3. Cannizzaro reaction
4. Perkin reaction

Answer: 1. Aldol condensation

Question 27. Which of the following will yield acetaldehyde?

1. The dry distillation of calcium acetate
2. The reduction of acetic acid by LIAIH
3. The oxidation of isopropyl alcohol by K₂Cr₂O₇/H₂SO₄
4. The ozonolysis of 2-butene

Answer: 4. The ozonolysis of 2-butene

Question 28. Which of the following reagents is used to distinguish between formic acid and acetic acid?

1. Phosphorus pentachloride
2. Sodium
3. Grignard reagent
4. Tollens reagent

Answer: 3. Grignard reagent

Question 29. Carbon dioxide is evolved when propanoic acid is treated with a NaHCO₃ solution. The carbon atom of CO₂ results from the

1. Methyl group
2. Carboxylic acid group
3. Methylene group
4. Bicarbonate

Answer: 4. Bicarbonate

Question 30. Which of the following does not reduce Fehling’s solution?

1. Formic acid
2. Acetic acid
3. Formaldehyde
4. Acetaldehyde

Answer: 2. Acetic acid

Question 31. An organic compound (X), on being heated with K₂Cr₂O, and H₂SO₄ gives another compound (Y). The latter on heating with I, and Na₂CO₃ solution forms an iodoform. Among the following, which one could be the compound (X)?

1. CH₃COCH₃
2. CH₃OH
3. CH₃CHO
4. CH₃CHOHCH₃

Answer:  4. CH₃CHO

Question 32. Which of the following is used to distinguish between formic acid and acetic acid?

1. Sodium
2. Mercuric chloride
3. Sodium ethoxide
4. 2,4-Dinitrophenylhydrazine

Answer: 2. Mercuric chloride

Question 33. An ester is hydrolysed by KOH and acidified to get a white precipitate. The ester is

1. Methyl acetate
2. Ethyl acetate
3. Ethyl formate
4. Ethyl benzoate

Answer: 4. Ethyl benzoate

Question 34. What are the products formed in the following reaction? \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{COOCH}_3 \stackrel{\mathrm{LiAlH}_4}{\longrightarrow}\)

1. C₆H₅COOCH and CH₃OH
2. C₆H₅C₃OOH and CH₃OH
3. C₆H₅CH₂OH and CH₃CHO and CH₃COOH
4. All of these

Answer: 4. C₆H₅CH₂OH and CH₃CHO and CH₃COOH

Biomolecules

All living beings are made up of complex molecules called biomolecules. Biomolecules not only help make up the structure of the body but also provide the energy required to carry out life processes. Examples of biomolecules are carbohydrates, proteins, nucleic acids and lipids. Apart from biomolecules, some simple molecules like vitamins and mineral salts play an important part in the functioning of living beings.

The study of these molecules and their interaction is called biochemistry.

Carbohydrates

Carbohydrates are compounds with the general formula C_n (H₂O)_m · Originally, they were thought to be hydrates of carbon, hence the name. However, they are not considered to be so any more for the following reasons. 1. Carbon does not form hydrates.

Some carbohydrates, like rhamnose (C₆H₁₂O₅) and deoxyribose (C₅H₁₀O₄

Several compounds, such as formaldehyde (CH₂O) and acetic acid (C₂H₄O₂), have the same general formula as carbohydrates but differ from them in their properties.

In terms of their functional groups, carbohydrates are polyhydroxy aldehydes or polyhydroxy ketones, or compounds which yield polyhydroxy aldehydes and polyhydroxy ketones on hydrolysis. The simplest carbohydrate is glyceraldehyde

⇒\(\left[\mathrm{C}_3\left(\mathrm{H}_2 \mathrm{O}\right)_3\right]\)

Carbohydrates are mainly produced by plants. In nature, C₆H₁₂O₆ (glucose) is produced by photosynthesis. Cellulose, which makes up the cell wall of plant cells, is a carbohydrate. Carbohydrates are an important constituent of the food we eat (they are found in rice, potatoes and bread, among other things). They provide us with the energy we require to carry out our life processes.

Classification And Nomenclature

Carbohydrates may be classified as monosaccharides (containing 1 sugar molecule), disaccharides (containing 2 sugar molecules) and polysaccharides (containing many sugar molecules). The names of carbohydrates have an ‘ose’ at the end, for example, glucose, fructose and sucrose.

Monosaccharides are the simplest sugars, and cannot be broken down or hydrolysed into simpler ones. They contain three to nine carbon atoms and are further categorised as trioses, tetroses, pentoses, hexoses, etc. Functionally, those containing an aldehydic group are known as aldoses and those with a ketonic group, are ketoses.

Often, the nature of the carbonyl functional group and the number of carbon atoms present in a monosaccharide are also indicated, example , aldopentoses, aldohexoses, ketopentoses and ketohexoses.

Carbohydrates which on hydrolysis give two to nine monosaccharide units are called oligosaccharides. They are further categorised as disaccharides, trisaccharides, etc., depending upon the number of monosaccharides obtained on hydrolysis.

Disaccharides are hydrolysed to give two molecules of monosaccharides, which may be the same or different. For instance, maltose gives two molecules of glucose, while sucrose yields one molecule each of glucose and fructose.

⇒ \(\underset{\text { Maltose }}{\mathrm{C}_{12} \mathrm{H}_{22} \mathrm{O}_{11}}+\mathrm{H}_2 \mathrm{O} \rightarrow \underset{\text { Glucose }}{2 \mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}\)

⇒ \(\underset{\text { Sucrose }}{\mathrm{C}_{12} \mathrm{H}_{22} \mathrm{O}_{11}}+\mathrm{H}_2 \mathrm{O} \rightarrow \underset{\text { Glucose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}+\underset{\text { Fructose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}\)

Trisaccharides (For example, raffinose) are hydrolysed to yield three molecules of monosaccharides.

⇒ \(\underset{\text { Raffinose }}{\mathrm{C}_{18} \mathrm{H}_{32} \mathrm{O}_{16}}+\underset{\text { Galactose }}{2 \mathrm{H}_2 \mathrm{O}} \rightarrow \underset{\text { Glucose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}+\underset{\text { Fructose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}+\underset{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}{\text { Gluction }}\)

Polysaccharides are high-molecular-weight carbohydrates that contain several monosaccharide units. In contrast to monosaccharides and disaccharides, which are water-soluble and sweet in taste, polysaccharides are tasteless, water-insoluble substances. The hydrolysis of a polysaccharide yields many molecules of monosaccharides. For example, starch gives many molecules of glucose.

⇒ \(\underset{\text { Starch }}{\left(\mathrm{C}_6 \mathrm{H}_{10} \mathrm{O}_5\right)_n+n \mathrm{H}_2 \mathrm{O} \rightarrow n \mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}\)

Carbohydrates which are sweet in taste are called sugars and those that are not are called nonsugars. Monosaccharides and disaccharides are sugars and polysaccharides are nonsugars.

Carbohydrates may also be classified as reducing and nonreducing sugars. All carbohydrates which reduce Fehling’s solution and Tollens reagent are called reducing sugars. All monosaccharides (aldose or ketose) are reducing sugars.

For example, glucose reduces Fehling’s solution to Cu₂O (red precipitate) and Tollens reagent to metallic silver. Glucose also reduces Benedict’s solution (an aqueous solution of CuSO₄ and sodium citrate) to Cu₂O (red precipitate).

This reaction is the traditional one used for the diabetes test in which urine is tested for glucose. Fructose (an a-hydroxy ketone) also responds positively to these tests because a-hydroxyketones, in general, are oxidised very easily to diketones by these reagents.

Maltose and lactose are reducing sugars as they reduce Fehling’s solution and Tollen’s reagent. These can produce a free aldehydic group in solution.

Sugars in which the carbonyl group is tied up in an acetal linkage are nonreducing sugars. Sucrose is an example of a non-reducing sugar.

Monosaccharides

Monosaccharides are crystalline substances and exhibit many reactions characteristic of the carbonyl and hydroxyl groups. They usually contain asymmetric carbon atoms, and exist as several optical isomers.

Glyceraldehyde is an aldotriose with one asymmetric carbon atom and exists in the (+) and (−) forms. It is chosen as a standard in describing the configurations of higher monosaccharides.

The D and L configurations (1 and 2) of glyceraldehyde are given below.

The sugars related to D-glyceraldehyde (1) form the D-series and those that are derived from L-glyceraldehyde (2) form the L-series.

Glucose

Glucose is the most widely occurring monosaccharide in nature and is found in the free state in sweet fruits and honey. Glucose was originally isolated from grapes. Glucose, because of its origin, is sometimes called grape sugar. It is also obtained by the hydrolysis of starch and cellulose. The alternative name dextrose originated from the fact that the common form of glucose rotates a plane of polarised light to the right, i.e., it is dextrorotatory.

Glucose is involved in the metabolic activities of living organisms. In the blood stream, a definite concentration of glucose must be maintained because both an excess and a deficiency are harmful. Excess glucose is excreted in urine. The concentration of glucose in the body is maintained by the action of insulin.

Preparation

On hydrolysis with dilute HCl or dilute H₂SO₄ in the presence of alcohol, sucrose (cane sugar) gives glucose and fructose in equal amounts.

⇒ \(\mathrm{C}_{12} \mathrm{H}_{22} \mathrm{O}_{11}+\mathrm{H}_2 \mathrm{O} \stackrel{\mathrm{H}^{+}}{\longrightarrow} \underset{\text { Glucose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}+\underset{\text { Fructose }}{\mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6}\)

Glucose is obtained on a commercial scale from the hydrolysis of starch in the presence of a mineral acid.

⇒ \(\underset{\text { Starch }}{\left(\mathrm{C}_6 \mathrm{H}_{10} \mathrm{O}_5\right)_n}+n \mathrm{H}_2 \mathrm{O} \underset{393 \mathrm{~K}, 2-3 \mathrm{~atm}}{\stackrel{\mathrm{H}_2 \mathrm{SO}_4}{\longrightarrow}} n \mathrm{C}_6 \mathrm{H}_{12} \mathrm{O}_6\)

Starch is hydrolysed with dilute H₂SO₄ The mixture is heated under pressure. When the hydrolysis is complete, the excess acid is neutralised with Ca(OH)2 and filtered. The filtrate is decolourised with animal charcoal, filtered and finally concentrated and cooled to get crystals of glucose.

Structure Of Glucose

1. Analytical data and molecular weight suggest that the molecular formula of glucose should be C₆H₁₂O₆.

2. On prolonged heating with HI, glucose gives n-hexane, indicating that all six carbon atoms are linked in a straight chain.

3. Glucose reacts with hydroxylamine to form an oxime. This suggests the presence of a carbonyl group.

4. On mild oxidation with bromine water, glucose is converted to carboxylic acid (gluconic acid), which has six carbon atoms. This indicates that the carbonyl group present in glucose is an aldehydic group.

5. With acetic anhydride, glucose yields a pentaacetate derivative.

This shows the presence of five hydroxyl groups in the glucose molecule. Since glucose is stable, all five hydroxyl groups are attached to different carbon atoms.

6. On strong oxidation with HNO₃, glucose yields saccharic acid (a dicarboxylic acid).

This reaction indicates the presence of a primary alcoholic group (-CH₂OH).

On the basis of the above reactions, the following open-chain structure may be assigned to glucose.

In Structure 1, there are four asymmetric carbon atoms indicated by an asterisk.

The spatial arrangement of five hydroxyl groups in glucose (1) was established by Fisher on the basis of his study of different reactions.

The prefix D- before glucose (2) indicates that the hydroxyl group attached to the bottom asymmetric carbon atom is on the right-hand side and it would be L-glucose if the hydroxyl group were on the left. Usually, D- and L- configurations are assigned to sugars by comparing their structures with the configuration of D- of D- and L- glyceraldehyde.

It must be remembered that, here, the symbols D- and L- refer to the configuration of the compound and have no relationship with the sign of rotation.

Cyclic structure of glucose:

The structure of D-glucose (2) accounts for most of its reactions satisfactorily but fa to explain the following facts.

1. The structure shows the presence of an aldehydic group but the compound does not respond to the Schiff test nor does it form a bisulphite addition compound with NaHSO₃.

2. D-glucose forms two isomeric pentacetates which fail to undergo condensation with NH₂OH.

3. D-glucose itself exists in two isomeric forms known as α- and β-D-glucose, which have different specific rotations. This phenomenon of change in specific rotation is termed mutarotation.

Specific rotation

Specific rotation [a] is defined as the rotation in degrees brought about by a solution containing 1 g of a substance in 1 mL of solution, examined in a polarimeter tube 1 decimetre long.

⇒ \([\alpha]=\frac{\text { observed rotation }}{\text { tube length }(\mathrm{dm}) \times \text { concentration }(\mathrm{g} / \mathrm{mL})}\)

α -D-glucose → α -D-glucos e ←β -D-glucose

[α]_D = +112° → [α]_D = +52° → [α]_D = + 19°

α -D-glucose (m.p. 419 K) is obtained by crystallisation from a concentrated solution of glucose at 303 K while β-D-glucose (m.p. 423 K) is obtained by crystallisation from a hot and saturated aqueous solution of glucose at 371 K.

It appears that in D-glucose the aldehydic group is not free. Rather it forms a cyclic hemiacetal with the —OH group originally situated at C₅. As the aldehydic group enters into hemiacetal formation, the aldehydic carbon becomes asymmetric.

Hence, two oxide ring structures differing in their C₁ configuration are possible. Such diastereomers, which differ in their C₁ configuration only, are known as anomers. An equilibrium mixture is obtained containing both the anomers as well as the open-chain form.

This interconversion is a manifestation of the phenomenon of mutarotation.

Haworth proposed a pyranose structure for these two anomeric forms (α- and β-). These structures resemble the six-membered heterocyclic pyran ring.

Fructose

Fructose is a ketohexose. In nature, it is found, along with glucose, principally in fruits and honey. It is also formed by the hydrolysis of table sugar. Fructose forms a furanose ring and is the sweetest of all the sugars. It is also called laevulose, indicating its laevorotatory property.

Structure

1. The molecular formula of fructose is C₆H₁₂O₆
2. It forms an oxime with hydroxylamine. This shows that it contains a carbonyl group.
3. The oxidation of fructose gives a mixture of glycolic acid, tartaric acid and trihydroxyglutaric acid (all of which have fewer carbon atoms than fructose). Therefore, it must be a ketone.
4.  On acetylation, fructose gives a pentaacetate, proving the presence of five hydroxyl groups.
5.  The reduction of fructose (Pd/H₂) yields a hexahydric alcohol, which on further reduction with hot HI gives n-hexane. Therefore, six carbon atoms of fructose form a straight chain.
6. On treatment with HCN, fructose gives cyanohydrin, which on hydrolysis yields the corresponding acid. The resulting acid on reduction with hot HI gives 2 – methylhexanoic acid (3). This shows that the carbonyl group in fructose is adjacent to the terminal carbon.

Considering all the facts, the open-chain structure (4) may be assigned to fructose.

The structure of D-(-)-fructose (4) (the minus sign indicates its laevorotatory nature) accounts for most of the reactions satisfactorily but is unable to explain the following facts.

1. It does not add on to NaHSO₃ as ketones do.
2. It shows mutarotation.
3. It forms two isomeric fructosides.

All these can be accounted for by a ring structure for fructose. The C=O group of fructose reacts with the -OH group at C₅ to form a five-membered ring and is named as furanose. The two furanose structures resemble the five-membered heterocyclic furan ring.

Haworth represented the above two cyclic structures of fructofuranose as follows.

Disaccharides

A disaccharide is a compound that can be hydrolysed to two different monosaccharides or two molecules of the same monosaccharide. Three important disaccharides are sucrose, lactose and maltose. All are isomers of each other and have the empirical formula C₁₂H₂₂O₁₁.

In a disaccharide, the two monosaccharides are joined together by a glycoside linkage. A glycoside bond is formed when two monosaccharides are joined together by an oxide linkage (-O) formed by the loss of a
water molecule.

Sucrose (nonreducing)

Sucrose is the technical name for table sugar (also called cane or beet sugar). Upon hydrolysis, sucrose yields an equimolar mixture of the monosaccharides D-(+)-glucose and D-(-)-fructose.

Sucrose is composed of an α-glucose plus β-fructose. When these two molecules are joined together a water molecule is released.

The OH group on C_n of a-glucose is bonded to the OH group attached to C₂ of β-fructose. This is called a 1- linkage. The oxygen atom bridging the two monosaccharides constitutes a glycoside bond.

Sucrose is dextrorotatory (optical rotation = +66) and the equilibrium mixture of glucose has an optical rotation of +52°, while fructose has a large negative rotation of -92°. At the end of the hydrolysis of sucrose, the equimolar mixture of glucose and fructose has a negative rotation (it is laevorotatory). Thus, the reaction proceeds with an inversion of rotation from a positive to a negative value. This is called the inversion of sucrose and the product mixture is called inverted sugar.

Maltose (reducing)

Maltose, called malt sugar, is found in the germinating seeds of barley or malt. Upon hydrolysis, it yields two molecules of glucose.

Maltose has a 1 → 4 linkage between two a-glucose molecules. The glycosidic 1-hydroxy group of the second molecule of glucose is free and can produce an aldehydic group at C₁ in the solution.

Therefore it shows a reducing property and is called a reducing sugar. Like sucrose, maltose is easily fermented into ethyl alcohol and CO₂

Lactose (reducing)

Lactose, also called milk sugar, is found in the milk of all mammals. Upon hydrolysis, it yields glucose and galactose.

Lactose + H₂O→glucose + galactose

In lactose, the OH group on C₁ of β-D-galactose is bonded to the OH group on C₄ of β-D-glucose. This is a 1 → 4 linkage.

The glycosidic hydroxy group of C₁ of the second molecule of glucose is free to produce an aldehydic group located at C₁. Therefore, lactose shows reducing properties and is said to be a reducing sugar.

Cow’s milk usually contains about 5% lactose by volume whereas human milk contains about 7%. Milk turns sour if kept for some time at 35°C because of the bacteria present in the air. These bacteria convert the lactose of milk into lactic acid, which is sour.

Polysaccharides

Polysaccharides are complex polymers. They have a high molecular weight and are made up of several monosaccharide (D-glucose) units linked together through oxygen atoms. They occur widely in plants and animals. Two important polysaccharides are starch and cellulose, both of which can be represented by the general formula (C₆H₁₀5)_n. Polysaccharides do not exhibit the characteristic reactions of the aldehyde group.

Starch

Plants store energy mainly in the form of starch. It forms the most important source of carbohydrates in the food we eat. It is found in wheat, rice, potatoes and some other vegetables.

Starch is insoluble in water, and forms a colloidal dispersion. Starch hydrolyses to form a number of α-D(+)- glucose molecules. It is not homogeneous. It consists of 15-20% amylose, which has a straight chain, and amylopectin (80-85%), which has a great deal of branching.

The amylose polymer consists of 200-1000 α-D(+)-glucose molecules joined by a (1→4) glycosidic linkages (Figure 14.8). Amylose is soluble in water, and gives a blue colour with iodine. Amylopectin, which is insoluble in water, consists of a number of amylose chains joined by a (1→6) glycosidic linkages.

Starch hydrolyses through the following stages.

Starch → dextrin → maltose → glucose

In the laboratory, the degree of hydrolysis can be observed by testing the solution with an iodine reagent. Starch reacts with this reagent to produce a deep blue-black colour while maltose and glucose produce no colour change.

As a fruit ripens, starch is hydrolysed to glucose and the fruit becomes sweet. Unlike cellulose, starch can be hydrolysed by enzymes. If you chew bread thoroughly before swallowing it, it will taste sweet. The sweetness is due to the sugar formed from the hydrolysis of starch.

Cellulose

Cellulose is present only in plants and is the most widely occurring organic substance found among them. The cell wall of a plant is mainly cellulose. Cellulose also forms a considerable part of cotton, wood and jute.

Cellulose is a polymer of ẞ-glucose. It is insoluble in water. A molecule of cellulose has a linear chain. On complete hydrolysis, cellulose yields D(+) glucose only. The D(+) glucose units in cellulose are 1,4-B-linked.

The human digestive tract breaks down starch to glucose but does not contain the enzymes required to hydrolyse B-glucose linkages and thus cellulose cannot be digested by human beings. Various derivatives of cellulose, such as cellulose nitrate and cellulose acetate, find commercial use. Cellulose nitrate is used to prepare smokeless gunpowder. Cellulose acetate can be spun into yarn or extruded into film (cellophane).

Glycogen

Starch is converted to a-glucose by animal metabolism. Glucose is repolymerised to form glycogen in the liver. Glycogen is also found in muscles and the brain. When exercise depletes blood sugar, the hydrolysis of liver glycogen maintains the normal glucose content of the blood. Glycogen consists of branched chains of glucose molecules. It is also called animal starch because its structure is similar to that of amylopectin. However, there is more branching in glycogen than in amylopectin.

Example 1:

1. Why is glucose soluble in water? Explain.
2.  How do you explain the absence of an aldehydic group in glucose pentaacetate?

Solution:

1. Glucose contains five hydroxyl groups, which form intermolecular hydrogen bonds with wat
2. In an aqueous solution, D-(+)-glucose may be regarded as the equilibrium mixture of the following three forms.

During the acetylation of glucose, the anomeric hydroxyl group at C1 is acylated and hence glucose pentaacetate can no longer attain the open-chain form. Thus, there is no aldehydic group.

Proteins

Approximately 16% of the total weight of a human being is protein. With the exception of water, which comprises 65% of our body weight, no other material constitutes more of the body than does protein. Among the main sources of protein are meat, fish, pulses, cheese and soya.

Many different proteins are responsible for the body’s innumerable functions. For example, the protein myoglobin in muscle tissue stores oxygen until the muscle cells need it. The red blood cells contain the protein haemoglobin, which takes oxygen from the lungs to the tissues.

There are proteins in the saliva, gastric juices, and intestinal juices, all of which help digest food. The pituitary gland secretes a protein, called human growth hormone, which regulates growth. Other hormones (also proteins), control processes in reproduction.

Certain cells in the pancreas secrete insulin, a protein that regulates the amount of sugar in blood. Human skin is made of protein. Thus proteins are involved in all life processes. Since they are fundamental to the living system, these compounds were given the name ‘protein’, from the Greek proteins, which means ‘primary’ or first.

The protein molecules present in animal and plant tissues have large numbers of C, H, O and N atoms and take up a considerable amount of space. Many proteins contain more than ten thousand atoms. Although they vary greatly in size, a protein with a length of 44 Å, a height of 44 Å and a width of 25 Å is considered relatively small.

Amino Acids (The Building Blocks Of Proteins)

How the atoms in a protein molecule are put together is of great concern to scientists. To gain an insight into the nature of proteins, a protein was heated with a solution of hydrochloric acid for a long period of time to break some bonds in the protein molecule.

The reaction mixture was found to contain a variety of smaller molecules. These molecules were isolated and examined, and were given the name amino acids. Amino acids contain an amino group and a carboxyl group. The formula and structure of glycine, a typical amino acid, is NH₂CH₂COOH.

Examination of the reaction mixture revealed other amino acids as well as glycine. There are 20 different amino acids known to exist in the various proteins.

Proteins are condensation polymers of the amino acid monomers. Amino acids which occur in nature have an amino group (-NH₂) attached to an a-carbon atom (the carbon of the first —CH₂– group attached to -COOH).

These amino acids differ from each other-they have distinctive side chains attached to the a-carbon atom replacing the H atom of glycine. An amino acid is often represented by the following general structure.

Where R may be aliphatic, aromatic or heterocyclic.

In all amino acids except glycine, the a-carbon atom is bonded to four different atoms or groups. Any molecule which contains a carbon atom bonded to four different groups is one of a pair of optical isomers.

One optical isomer is designated as the L isomer and the other as the D isomer. The amino acids of proteins are all L isomers.

Naturally occurring amino acids from plant and animal sources have the L configuration and are designated as L(+) or L(-), depending upon their behaviour towards a plane of polarised light.

Amino acids are often represented by a three-letter symbol, for example, Gly for glycine, ala for alanine, and so on.

Classification Of Amino Acids

Amino Acids Are Classified In Three Different Ways.

1. As you know, amino acids are compounds containing an amino as well as an acidic (mostly carboxylic) group. A simple classification is based on the position of the amino group with respect to the carboxylic group.

Thus a-amino acids have an amino group attached to the a-carbon with respect to the carboxylic group, β-amino acids contain the amino group attached to the β-carbon, and so on.

In this chapter, we shall discuss only amino acids as these are the building units of proteins.

2. Most amino acids have only one basic and one acidic group and exhibit amphoteric properties. They are called neutral amino acids. In some cases, however, an amino acid may contain more carboxylic groups than amino groups.

They are termed acidic amino acids, examples being aspartic and glutamic acids. Amino acids with a greater number of basic (amino) groups than acidic groups, for example, lysine, arginine, and histidine, are basic in nature.

3. Certain amino acids can be synthesised in the body while others have to be obtained through the food we eat. The former are called nonessential amino acids while the latter are called essential amino acids.  gives the structures, names and abbreviations of some common amino acids that have been isolated by protein hydrolysis. Essential amino acids are marked with an asterisk.

The most common natural amino acids: 

Electrical Properties-Zwitterion Structure

Amino acids are high-melting solids, which, because of their polar groups, are insoluble in organic solvents but soluble in water. They behave like salts rather than simple amines or carboxylic acids.

Since the carboxylic acid group is acidic and the amino group is basic, amino acids actually exist as dipolar ions (zwitterions), rather than in the un-ionised form.

From Amino Acids To Proteins (The Peptide Bond)

Proteins are formed by the linking together of amino acids. The amino group of one molecule reacts with the carboxyl group of another, with the elimination of a molecule of water. When two amino acids combine, they form a dipeptide.

If three amino acids combine, they form a tripeptide, when four combine, they form a tetrapeptide, and so on. When more than ten combine, they are said to form a polypeptide.

The -CONH group (the amide group), which joins amino acids together, is called a peptide link. A polypeptide molecule might have the structure given in below

A polypeptide has 1 free -NH₂ at one end of the chain and 1 free -COOH group at the other end. The amino end is referred to as the N-terminal and the carboxylic acid end as the C-terminal.

A polypeptide with more than a hundred amino acid residues, with a molecular mass higher than 10,000 u, is called a protein. In a polypeptide or protein, the peptide bond is the strongest chemical bond.

Classification Of Proteins

• Proteins may be categorised as fibrous and globular.
• Fibrous proteins are water-insoluble. They have long threadlike molecules that lie side by side to form fibres. Typical examples are keratin (present in hair, wool, silk) and myosin (present in muscles).
• The polypeptide chains in fibrous proteins are held together by hydrogen and disulphide bonds.
• Globular proteins are soluble in water and dilute acids, bases and salt solutions. Molecules of globular proteins are folded into spherical units. Albumin and plasma proteins are common examples of globular proteins.

Structure Of Proteins

The structure of proteins is studied at four different levels-primary, secondary, tertiary and quaternary. Each successive level is more complex than the previous one.

The Primary Structure

• In the context of the primary structure of a protein, we are concerned with the way amino acid residues join together to form chains. There are two aspects to this.
• The first of these is the geometry of the peptide link. Secondly, the sequence in which the amino acid residues appear in a chain is important.

The Secondary Structure

• In the context of the secondary structure of a protein, we are concerned with the arrangements of polypeptide chains, which results in a particular shape. This shape arises as a consequence of hydrogen bonding.
• The way in which the hydrogen bonds are arranged results in the formation of two possible structures—the a-helix structure and the β-sheet structure (or pleated-sheet structure).
• In the a-helix structure, hydrogen bonding within the chain twists it into a coil.
•   Hydrogen bonding occurs between the C=O group of one turn and the >N-H group of the turn below. An example of a protein with such a structure is keratin, which is found in hair and nails.
• In the pleated-sheet structure, hydrogen bonding occurs between different chains. The chains are arranged in the form of sheets of proteins type of structure is found in silk.

Tertiary structure

• The tertiary structure represents how the protein molecule is folded upon itself. It comes about on account of the folding and superposition of various secondary structures.
• The tertiary structure is found in two most important shapes-the globular and the fibrous. The secondary structure represents fibrous proteins.
• The folded molecule is held together by hydrogen bonding between side chains, salt bridges, disulphide bonds and other weak bonds. Myoglobin has an a-helical coil that is folded in upon itself.

Quaternary Structure

• Several polypeptide units, known as subunits (not always identical), can aggregate to form large complexes. The structure of the protein that results on account of the spatial arrangement of several subunits is known as the quaternary structure.
• Haemoglobin is composed of 4 protein chains that are held together by hydrogen bonding, salt bridges and other weak bonds.

Denaturation Of Proteins

• Under appropriate conditions the delicate three-dimensional structure of globular proteins may be disturbed. This process is called denaturation.
• Denaturation commonly occurs when the protein is subjected to extremes in temperature or when there is a change in pH. It is usually accompanied by a considerable decrease in the water solubility of the protein.
• An example is the coagulation that results in the hardening of the white and the yolk of an egg upon heating.
• Denaturation is essentially a disorganisation of the helical structure of the protein molecule caused by the breaking up of the cross-linked chains in the protein structure.
• Not only the hydrogen bonds but also the disulphide (-S-S-) bonds, salt bridges and other weak bonds are broken. This bond breaking results in loss of biological activity because the unique three-dimensional structure involving secondary and tertiary structures is destroyed.
• This is often accompanied by precipitation and coagulation. Remember that only the weak bonds of the protein molecules are broken and none of the peptide linkages are affected.

Enzymes

All life processes, such as the digestion of food, involve a series of reactions. These reactions occur very rapidly under mild conditions. These reactions, if performed in the laboratory, might take hours or days even under very vigorous conditions. Somehow the body manages to increase greatly the rate of these reactions without heating. This is achieved by the catalysis of biochemical reactions by a type of molecule known as an enzyme.

• Most enzymes are globular proteins, and a few are nonproteins. Apart from being rapid, the reactions involving enzymes are quantitative and highly specific—a single enzyme will catalyse only a specific metabolic reaction.
• One series of enzymes catalyses the breakage of the peptide bonds in proteins so that amino acids are formed.
• Enzymes in saliva begin the process of breaking down starch into a-glucose.
• Some enzymes catalyse the formation of blood clots when necessary; others dissolve the clots after a wound has healed. Certain enzymes help the body to fight infections. Fruits ripen because of the action of enzymes. As the list suggests, enzymes are involved in a variety of processes.
• An enzyme is commonly named by adding the suffix ‘ase’ to the name of the substrate with which it reacts. For example, the enzyme urease catalyses the hydrolysis of urea into carbon dioxide and ammonia while maltase catalyses the hydrolysis of maltose to D (+) glucose. Some enzymes are popularly known by their trivial names, for example, pepsin.
• Enzymes are classified according to the type of reaction they catalyse.

The major classes of enzymes are as follows:

1. Oxidoreductases catalyse oxidation-reduction reactions.
2. Transferases catalyse the transfer of a characteristic chemical group from one molecule to another.
3. Hydrolases catalyse the reaction of the substrate with water.
4. Isomerases catalyse various types of isomerisation.

An enzyme is a biological catalyst. It is required only in small quantities for the progress of a reaction. Like a chemical catalyst, an enzyme reduces the magnitude of activation energy of a reaction.

For example, the activation energy for the acid hydrolysis of sucrose is 6.22 kJ mol1, while it is only 2.15 kJ mol1 when hydrolysed by the enzyme sucrose.

Mechanism Of Enzyme Action

A number of active sites (cavities) are present on the surface of an enzyme. These active sites are characterised by the presence of functional groups such as -NH2, -COOH, -SH and -OH.

These functional groups form weak bonds, such as hydrogen bonds or van der Waals bonds, with the corresponding substrate. The shape of a substrate is complementary to that of the corresponding enzyme.

So an enzyme fits into a substrate just like a key fits into a lock. Thus, an enzyme-substrate complex is formed, which then decomposes to yield the products.

Coenzymes

• A coenzyme is a nonprotein substance, needed for enzyme activity, that forms part of certain enzymes.
• Vitamins frequently form part of the coenzyme molecule.

Factors Affecting Enzyme Activity

• Since most enzymes are proteins, any of the factors that denature proteins also prevent them from acting.
• Enzymes in the body are the most active at normal body temperature, 98.5°F or 37°C.
• Temperatures above normal reduce enzyme activity and enzymes stop acting at extremes of temperature. Temperatures below normal also reduce enzyme activity.
• Each enzyme is the most active at its own optimum pH. On either side of this pH, its activity is markedly decreased.

Vitamins

• Vitamins are organic compounds which are essential for normal growth in human beings but most of them are not synthesised by the human body.
• However, plants can synthesise nearly all vitamins. Although required in small quantities, a lack of vitamins in the diet causes various diseases, known as deficiency diseases.
• Therefore these substances must be part of the diet along with carbohydrates, fats, proteins and minerals. Remember, however, that an excess of vitamins is harmful and you should not take vitamin pills unless the doctor advises you to.
• Vitamins are denoted by letters of the alphabet. They are classed as either water-soluble or fat-soluble. The B-complex vitamins and vitamin C are water-soluble.
• Vitamins A, D, E and K are fat-soluble. The table lists certain vitamins, their sources and the corresponding deficiency diseases.

Example 2:

1. Why are amino acids high-melting solids and water-soluble?
2. Why can vitamin C not be stored in our body?
3. Where does the water present in an egg go after the egg is boiled?

Solution:

1. Amino acids exist as internal salts called dipolar ions or zwitterions.

Due to the polar nature of amino acids, their molecules are attracted to each other by a strong dipole-dipole force. Therefore, their melting points are high. Because of their dipolar ionic structure, amino acids are soluble in water.

2. Vitamin C is soluble in water and is readily excreted in urine.

3. Upon heating, the proteins in eggs undergo denaturation and then coagulation, causing hardening of the white and the yolk. The water present in the egg gets absorbed/adsorbed in the coagulated proteins through hydrogen bonding.

Nucleic Acids

• Nucleic acids are those substances that are responsible for the passing on of hereditary traits and for the synthesis of proteins. They are high-molecular-weight polymers, consisting of repeating units called nucleotides.
• Nucleotides are made up of three parts—a nitrogen base, a five-carbon sugar and a phosphoric acid residue. The bases of nucleotides are derived from either pyrimidine or purine.
• The bases derived from pyrimidine are thymine (T), cytosine (C) and uracil (U). Those derived from purine are adenine (A) and guanine (G).
• A typical nucleotide how nucleotides combine to form a nucleic acid chain.
• Ribonucleic acid (RNA) is produced in the nucleus and migrates to the cytoplasm. It is involved in protein synthesis. Also, the genetic material of some microorganisms, such as many viruses, is RNA.
• The nucleus also contains deoxyribonucleic acid (DNA), the substance which is responsible for cell replication and is sometimes called the genetic code.

Structure Of Nucleic Acids

Like proteins, RNA and DNA have a high molecular weight; molecular weights of up to 10 million have been observed. On hydrolysis, both types of nucleic acids yield phosphoric acid, a sugar and a mixture of bases derived from purine and those from pyrimidine.

The sugar obtained from RNA is B-D-ribose, while that obtained from DNA is B-D-2-deoxyribose. The major bases obtained from DNA are the purine bases adenine and guanine and the pyrimidine bases cytosine and thymine.

RNA yields mainly adenine, guanine, cytosine and another pyrimidine base, uracil.

The mild degradation of nucleic acid yields nucleotides. Each nucleotide contains one purine or pyrimidine base, one phosphate unit, and one pentose unit.

The phosphate unit may be selectively removed by further careful hydrolysis. Then the nucleotide is converted into a nucleoside, a molecule built up of a pentose joined to a purine or pyrimidine base.

In a nucleotide, C₁ of the sugar is joined to N₁ of a pyrimidine or N₉ of a purine; the phosphoric acid unit is present as an ester at C₅ of the sugar.

Example 3: Name the three products which are formed when a nucleotide from RNA containing adenine is hydrolysed.

Solution:

The three products are

1. Adenine,
2. β-D-ribose and
3. Phosphoric acid.

In a nucleic acid chain, the phosphoric acid is esterified to form a bridge between C₅ of the sugar of one nucleoside and C₃ of the sugar of another nucleoside.

In this way, the sugar-phosphate units can form a long backbone or framework, which bears purine and pyrimidine bases at regular intervals.

A typical segment of a DNA chain is given in below

• The manner in which the sugar, phosphate and bases are linked with one another in nucleic acids determines the primary structure of the nucleic acids.
• Nucleic acids have a secondary structure also. Watson and Crick in 1953 proposed the now-accepted double helical structure of DNA.
• According to their of two DNA analyses, the molecule actually consists of complementary strands which are twisted about a common axis as helices with the same chirality (handedness).
• Each adenine unit of one chain is specially hydrogen-bonded to a thymine of the opposite chain and each guanine of one chain is similarly bonded to a complementary cytosine unit.
• It should be noted that the base pairing is restricted by hydrogen bonding requirements.
• The hydrogen atoms in purine and pyrimidine bases have well-defined positions. Adenine cannot pair with cytosine because there would be two hydrogen atoms near one of the bonding positions and none at the other.
• Similarly, guanine cannot pair with thymine. The G-C bond is stronger by 50% than the A-T bond.
• The double helical structure of DNA is shown schematically in Figure 14.29. The helical strands represent the sugar-phosphate backbones, which are held nicely in place by hydrogen bonding between the complementary base units.
• The order of the bases on the chain of the DNA molecule is extremely significant biologically. It is the fundamental unit of the hereditary information carried by genes.
• There are three different kinds of RNA molecules— messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA).
• The RNA molecule is helical and single-stranded but occasionally small portions of it have a double-helical structure.
• This feature is observed when part of the molecule folds back upon itself to form complementary base pairs.

DNA Fingerprinting

Just as every person in the world can be positively identified by his or her fingerprints, so can every individual be identified nowadays by DNA fingerprinting.

This is because the base sequence of the DNA of every individual is unique and cannot be altered by any means.

DNA fingerprinting is now used to:

1.  Identify Criminals In Forensic Laboratories,
2.  Determine The Paternity Of An Individual, And
3.  Identify Dead Bodies By Comparing The Dnas Of Parents Or Children.

Biological Functions Of Nucleic Acids

• The DNA regulates two life processes. First, it can duplicate itself and secondly, it acts as a template for providing RNAs, which carry out protein synthesis.
• A molecule of DNA reproduces (or duplicates) itself by a remarkably simple mechanism. The two strands of the DNA molecule dissociate (an ‘unzipping’ process).
• Each strand then serves as a template for the synthesis of a complementary, new strand (Figure 14.30). The new (daughter) DNA molecules are identical to the original (parent) molecule—they contain all the original genetic information.
• The synthesis of identical copies of DNA is called replication. This process is the reason why children look much more like their relatives than like animals or trees.
• DNA has not only the critical function of reproducing itself, but also the important function of transferring information by causing the synthesis of a second type of nucleic acid called RNA.
• This transfer of information is called transcription. The major function of RNA is to transfer this information from nucleic acids to proteins, a process called translation.
• The three different kinds of RNA molecules-messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA)-perform different functions.

Biomolecules Multiple-Choice Questions

Question: 1. A carbohydrate contains at least

1. 6 Carbons
2. 3 Carbons
3. 4 Carbons
4. 2 Carbons

Answer: 2. 3 Carbons

Question: 2. Which of the following is laevorotatory?

1. Glucose
2. Fructose
3. Sucrose
4. None Of These

Answer: 2. Fructose

Question: 3. Which of the following carbohydrates forms a silver mirror on being treated with Tollens reagent?

1. Sucrose
2. Fructose
3. Glucose
4. Starch

Answer: 3. Glucose

Question: 4. Which of the following carbohydrates is an essential component of plant cells?

1. Starch
2. Cellulose
3. Sucrose
4. Vitamins

Answer: 2. Cellulose

Question: 5. The hydrolysis of sucrose leads to

1. Saponification
2. Hydration
3. Esterification
4. Inversion

Answer: 4. Inversion

Question: 6. Which of the following is the sweetest of all the sugars?

1. Sucrose
2. Maltose
3. Fructose
4. Lactose

Answer: 2. Maltose

Question: 7. On hydrolysis, maltose yields

1. Glucose And Mannose
2. Galactose And Glucose
3. Glucose
4. Mannose

Answer: 3. Glucose

Question: 8. The function of enzymes is to

1. Provide Energy
2. Provide Immunity
3. Transport Oxygen
4. Catalyse Biochemical Reactions

Answer: 4. Catalyse Biochemical Reactions

Question: 9. A deficiency of which of the following may cause night blindness?

1. Vitamin B₁₂
2. Vitamin A
3. Vitamin C
4. Vitamin E

Answer: 2. Vitamin A

Question: 10. Which of the following functional groups is/are present in amino acids?

1. -COOH group
2. -NH₂ group
3. -CH₃ group
4. ‘a’ and ‘b’

Answer: 4. ‘a’ and ‘b’

Question: 11. What is the order in which a base, a phosphate and a sugar are arranged in nucleic acids?

1. Base-Phosphate-Sugar
2. Phosphate-Base-Sugar
3. Sugar-Base-Phosphate
4. Base-Sugar-Phosphate

Answer: 4. Base-Sugar-Phosphate

Question: 12. Which of the following is related to steroids?

1. Vitamin E
2. Vitamin K
3. Vitamin B
4. Vitamin D

Answer: 4. Vitamin D

Question: 13. A deficiency of vitamin C causes

1. Beriberi
2. Night Blindness
3. Rickets
4. Scurvy

Answer: 4. Scurvy

Question: 14. Which of the following is capable of forming a zwitterion?

1. H₂NCH₂COOH
2. CH₃COOH
3. CH₃CH₂NH₂
4. CCl₃NO₂

Answer: 1. H₂NCH₂COOH

Question: 15. Which of the following are generally not produced in our body?

1. Enzymes
2. Vitamins
3. Proteins
4. Hormones

Answer: 2. Vitamins

Question: 16. Nucleic acids are

1. Polymers Of Nucleotides
2. Polymers Of Nucleosides
3. Polymers Of Purine Bases
4. Polymers Of Phosphate Esters

Answer: 1. Polymers Of Nucleotides

Question: 17. The bases common to DNA and RNA are

1. Adenine, Cytosine And Uracil
2. Guanine, Adenine And Cytosine
3. Guanine, Uracil And Thymine
4. Adenine, Thymine And Guanine

Answer: 2. Guanine, Adenine And Cytosine

Question: 18. The functions of DNA are

1. To Synthesise Rna
2. To Synthesise Proteins
3. To Carry Genetic Information From Parent To Offspring
4. A, B And C

Answer: 4. A, B And C

Question: 19. The purine base present in RNA is

1. Guanine
2. Thymine
3. Cytosine
4. Uracil

Answer: 4. Uracil

Question: 20. In respect of which base does RNA differ from DNA?

1. Thymine
2. Adenine
3. Cytosine
4. Guanine

Answer: 1. Thymine

Question: 21. Insulin is

1. An Amino Acid
2. A Protein
3. A Carbohydrate
4. A Lipid

Answer: 2. A Protein

Question: 22. The secondary structure of a protein refers to the

1. Fixed Configuration Of The Polypeptide Backbone
2. A-Helical Backbone
3. Hydrophobic Interactions
4. Sequence Of A-Amino Acids

Answer: 2. A-Helical Backbone

Question: 23. Which of the following is/are disaccharides with the molecular formula C₁₂H₂₂O₁₁?

1. Cane Sugar
2. Fruit Sugar
3. Lactose
4. A Ketohexose

Answer: 1. Cane Sugar, 3. Lactose, 4. A Ketohexose

Question: 24. Fructose is

1. Grape Sugar
2. Laevulose
3. Raffinose
4. Maltose

Answer: 2. Laevulose, 3. Raffinose, 4. Maltose

Amines

Amines are derivatives of ammonia. Alkylamines are derived from ammonia by replacing one, two, or three of the hydrogen atoms of ammonia by alkyl groups. In arylamines, one, two, or three of the hydrogen atoms of ammonia are replaced by aryl groups. The amino group (NH₂, NH, or N) is present in a number of important substances. The most significant of them are amino acids, proteins, and alkaloids. Some alkaloids have medicinal properties and some are poisonous.

Morphine, one of the most effective painkillers known, quinine, an important drug for the treatment of malaria, and nicotine, the toxic component in tobacco, are among some of the alkaloids that have been isolated and used by mankind.

Many vitamins, antibiotics, and drugs contain amino groups. Adrenalin, a secondary amine, causes constriction of blood vessels and an increase in blood pressure. Novocaine (a quaternary ammonium salt) is frequently used as a local anesthetic by dentists. A well-known antihistaminic drug diphenylhydramine (Benadryl), is a tertiary amine.

Iodofore, a quaternary ammonium salt, is used as an antiseptic. The synthetic fiber nylon is made from two raw materials, one of which is a simple diamine. Benzene diazonium salts are useful intermediates for the preparation of a variety of aromatic compounds. Aniline, an aromatic amine, is used in the synthesis of various types of dyes. It is also used in the synthesis of sulpha drugs.

Amines Structure

In an amine, nitrogen is sp³ hybridized and the molecule is nearly tetrahedral. Of the four sp³-hybridised orbitals, three having one electron each form one sigma bond each with three alkyl groups or two alkyl groups and one hydrogen atom or one alkyl group and two hydrogen atoms.

The fourth hybridized orbital of nitrogen is completely filled with an electron pair and does not take part in bond formation. Therefore, the geometry of an amine is pyramidal, like that of ammonia.

The C-N-C bond angle in trimethylamine is 108°, less than the tetrahedral bond angle of 109.5°. The contraction in bond angle in trimethylamine is possibly due to repulsion between the electrons forming the lone pair and repulsion between the three alkyl groups.

Classification Of Amines With Examples

Amines are classified as primary (1°), secondary (2°), and tertiary (3°), depending on whether one, two, or three hydrogen atoms of ammonia have been replaced by an alkyl or aryl group.

The general formulae and functional groups of primary, secondary and tertiary amines:

In secondary and tertiary amines, the alkyl or aryl groups may be the same or different. Amines are said to be ‘simple’ when all the alkyl or aryl groups are the same, and ‘mixed’ when they are different.

Nomenclature

The common names of amines are derived by placing the suffix -amine after the name of the alkyl group. The names are written as single words. In the IUPAC system, primary aliphatic amines are named by adding the suffix -amine to the name of the corresponding alkane, the final ‘e’ of the name of the alkane being omitted. For example, methane-e+amine methanamine.

The common and IUPAC names of some primary amines:

In case of secondary aliphatic amines, the common name is derived by writing the names of the two alkyl groups in alphabetical order. When two identical groups are attached to the nitrogen atom, ‘di’ is prefixed to the name of the alkyl group. In the IUPAC system, secondary amines are named as N-substituted derivatives of alkanamines. The longest carbon chain containing an alkyl group attached to nitrogen is taken as the corresponding alkane of the alkanamine.

The common and IUPAC names of some secondary amines:

In the case of tertiary amines, the common name is derived by writing the names of the three alkyl groups in alphabetical order. When three identical groups are attached to the nitrogen atom, tri is prefixed to the name of the alkyl group. In the IUPAC system, tertiary amines are named N, N-disubstituted derivatives of alkanamines. The longest carbon chain containing an alkyl group attached to nitrogen is taken as the corresponding alkane of the alkanamine.

The common and IUPAC names of some tertiary amines:

Ethylmethylpropylamine N-Ethyl-N-methyl propanamide

The common and IUPAC name of the simplest aryl amine is aniline. It is also an accepted IUPAC name.

Simple derivatives are named substituted anilines. Also, in the IUPAC system, arylamines are named by adding the suffix ‘amine’ to the name of the arene after removing the ‘e’ of the arenes. Thus C₆H₅ NH₂ is named benzenamine.

The common and IUPAC names of some arylamines and substituted arylamines:

Some examples on IUPAC nomenclature:

1. \(\left(\mathrm{CH}_3\right)_3 \stackrel{3}{\mathrm{C}} \stackrel{2}{\mathrm{C}} \mathrm{H}_2 \stackrel{1}{\mathrm{C}} \mathrm{H}_2 \mathrm{NHCH}_3\)

N,3,3 – Trimethyllbutamine

The formula is expended as follows:

The compound is a secondary amine. Its longest chain has 4 carbons. So, it is an N-substituted butanamine. Here, one methyl group is attached to nitrogen (N) and two methyl groups are attached to C-3.

Therefore, its IUPAC name is N, 3, 3-Trimethylbutanamine.

2. 

The compound is a tertiary amine. Its longest chain has 4 carbons. So, it is an N, N-disubstituted butanamine. Here nitrogen is attached with one ethyl group and one methyl group. In alphabetical order, ‘ethyl’ would be placed before ‘methyl’. Therefore, the IUPAC name of the compound is N-Ethyl-N-methylbutanamine.

Example 1: What are the eight amines with the formula C₄H₁₁N? Classify them as primary secondary and tertiary and write their IUPAC names.

Solution:

Primary amines:

Secondary Amines

Tertiary Amines:

Methods Of Preparation From Alkyl Halides

Aliphatic amines can be prepared by heating alkyl halides with aqueous or alcoholic ammonia solution (excess) in a sealed tube at 373 K.

⇒ \(\mathrm{RX}+\text { conc. } \mathrm{NH}_3 \text { (excess) } \stackrel{\Delta}{\longrightarrow} \mathrm{R}^{+} \mathrm{H}_3 \mathrm{X}^{-}+\mathrm{NH}_3 \stackrel{-\mathrm{NH}_4 \mathrm{X}}{\longrightarrow} \underset{\text { Primary amine }}{\mathrm{RNH}_2}\)

Alkyl halides Mechanism:

This is a nucleophilic substitution reaction.

The free amine can also be obtained from the ammonium salt by treatment with NaOH.

⇒ \(\mathrm{R}-\stackrel{+}{\mathrm{NH}_3} \overline{\mathrm{X}} \stackrel{\mathrm{NaOH}}{\longrightarrow} \mathrm{R}-\mathrm{NH}_2+\mathrm{H}_2 \mathrm{O}+\mathrm{NaX}\)

The process of cleavage of the C-X bond by an ammonia molecule called ammonolysis. The following is the order of reactivity of alkyl halides towards nucleophilic reagents.

RI > RBr> RCl

If a large excess of an alkyl halide is present in the reaction mixture, the primary amine obtained reacts further with the alkyl halide. Then secondary and tertiary amines are formed, and finally a quaternary ammonium salt.

⇒ R-Br+ NH₃R-NH₂ + HBr

⇒ R-NH₂+ R-Br→ R₂NH + HBr

⇒ R₂ NH+R-Br→ R₃N+ HBr

⇒ R₃N+R-Br→R₄ N⁺Br^–

In this method a mixture of primary, secondary and tertiary amines and also a quaternary ammonium salt is obtained. However, the primary amine is obtained as the major product when a large excess of ammonia is used.

In normal conditions, an aryl halide does not react with ammonia as the halogen is firmly bound to the aryl ring. The reaction occurs under the conditions mentioned in the following chemical equation

By The Reduction Of Nitroalkanes, Cyanides (Nitriles), Amides And Oximes

From nitroalkanes

Nitroalkanes are reduced to primary amines by hydrogen in the presence of finely divided nickel, palladium or platinum as catalyst.

⇒ \(\mathrm{R}-\mathrm{NO}_2+3 \mathrm{H}_2 \stackrel{\mathrm{Ni}}{\longrightarrow} \mathrm{R}-\mathrm{NH}_2+2 \mathrm{H}_2 \mathrm{O}\)

Nitroalkanes are also reduced by LiAlH4 or Fe/HCl.

⇒ \(\mathrm{R}-\mathrm{NO}_2+6[\mathrm{H}] \stackrel{\mathrm{LiAlH}_4}{\longrightarrow} \mathrm{R}-\mathrm{NH}_2+2 \mathrm{H}_2 \mathrm{O}\)

LiAlH₄, is expensive and therefore Fe/HCl is preferred.

In the laboratory, nitrobenzene is reduced to aniline by Sn/HCI.

Aromatic nitro compounds are not usually reduced by LiAlH_4.

From alkyl cyanides (alkyl nitriles)

Alkyl cyanides are reduced to primary amines by LiAlH₄ or Pd/H₂

The reduction of an alkyl isocyanide forms a secondary amine.

From acid amides

Acid amides are reduced to primary amines by LiAlH₄.

⇒ \(\mathrm{R}-\mathrm{CONH}_2+4[\mathrm{H}] \stackrel{\mathrm{LiAlH}_4}{\longrightarrow} \mathrm{R}-\mathrm{CH}_2-\mathrm{NH}_2+\mathrm{H}_2 \mathrm{O}\)

The reduction of N-substituted amides by LiAlH₄ gives secondary amines.

Dialkyl substituted amides, on reduction with LiAIH₄ form tertiary amines.

Example 2: Write equations showing how the following conversions may be accomplished

Solution:

From oximes

The oximes of aldehydes and ketones are reduced to amines by Ni/H₂ or LiAlH₄.

From The Hofmann Bromoamide Degradation Reaction

Acid amides are converted into primary amines with the loss of one carbon atom by the action of hypobromite (Br₂/NaOH).

⇒ \(\underset{\text { Acid amide }}{\mathrm{R}-\mathrm{CONH}_2}+4 \mathrm{NaOH}+\mathrm{Br}_2 \rightarrow \underset{\text { Primary amine }}{\mathrm{R}-\mathrm{NH}_2}+2 \mathrm{NaBr}+\mathrm{Na}_2 \mathrm{CO}_3+2 \mathrm{H}_2 \mathrm{O}\)

Mechanism Of Hoffmann Bromide Degradation Reaction:

The conversion of the amide to the primary amine involves the migration of the alkyl or aryl group from the carbon atom to the electron-deficient nitrogen atom.

This is known as Hofmann rearrangement. The entire reaction is also called Hofmann degradation because the amine formed has one carbon atom less than the amide we start with.

On treatment with Br₂/NaOH, benzamide gives aniline.

C₆H₅CONH₂+ Br₂+ 4NaOH → C₆H₅NH₂+ Na₂CO₃ + 2NaBr + 2H₂O

Example: Illustrate the following processes by means of equations giving reagents and conditions.

1. Conversion of an amide to a primary amine with one carbon atom less
2. Conversion of an amide to a primary amine with the same number of carbon atoms

Solution: 

⇒ \(\mathrm{RCONH}_2+4 \mathrm{NaOH}+\mathrm{Br}_2 \rightarrow \underset{\text { (amine with one } \mathrm{C} \text { atom less) }}{\mathrm{R}-\mathrm{NH}_2}+2 \mathrm{NaBr}+\mathrm{Na}_2 \mathrm{CO}_3+2 \mathrm{H}_2 \mathrm{O}\)

⇒ \(\mathrm{RCONH}_2 \underset{2 . \mathrm{H}_3 \mathrm{O}^{+}}{\stackrel{1 . \mathrm{LiAlH}_4}{\longrightarrow}} \underset{\text { (amine with same number of } \mathrm{C} \text { atoms) }}{\mathrm{RCH}_2 \mathrm{NH}_2}\)

Gabriel phthalimide Synthesis

Gabriel phthalimide synthesis is used to prepare aliphatic primary amines. Phthalimide is acidic and reacts with alcoholic KOH to yield potassium phthalimide, which on being heated with an alkyl halide gives N-alkylphthalimide. On hydrolysis, N-alkyl phthalimide gives an amine and phthalic acid.

Example 3: Will Gabriel synthesis be useful for the preparation of t-butylamine? Explain.

Solution: No, because we cannot alkylate potassium phthalimide with (CH₃)₃ C-X. (By dehydrohalogenation, isobutylene will be formed).

Example 4: In each of the following, how will you obtain the final product from the starting material?

Solution:

Physical Properties

Lower aliphatic amines are gases or low-boiling liquids. Methylamine and ethylamine are gases. n-Propylamine is a liquid at room temperature.

1. Pure aniline is a colorless liquid that slowly turns brown due to atmospheric oxidation.
2. Diphenylamine (m.p. 327 K) and triphenylamine (m.p. 400 K) are solids.

Boiling point:

Primary and secondary amines are polar and participate in hydrogen bonding.

Since nitrogen is not as electronegative as oxygen, the nitrogen-hydrogen bond (N-H—N) is less polar than the oxygen-hydrogen bond (O-H—O). The boiling points of amines are, therefore, lower than those of alcohols of similar molecular weight, but higher than the boiling points of hydrocarbons and other compounds in which no hydrogen bonding is possible, e.g., tertiary amines. We will illustrate the trend in boiling points by considering the examples of n-pentane, butylamine, and n-butyl alcohol.

⇒ CH₃ CH₂CH₂CH₂CH₃-( n-Pentane mol. wt. 72b.p. 309 K)(no hydrogen bonding)

⇒ CH₃ CH2CH₂CH₂NH₂ Butylamine mol. wt. 73 b.p. 351 K

⇒ CH₃CH₂CH₂CH₂OH n-Butyl alcohol mol. wt. 74 b.p. 391 K

The molecules of primary amines are associated due to intermolecular hydrogen bonding between the nitrogen of one molecule and the hydrogen of another. The molecules of secondary amines are also associated in a similar fashion but to a lesser extent than in primary amines.

A primary amine has two hydrogen atoms available for hydrogen bonding as compared to one hydrogen in a secondary amine. The molecules of tertiary amines are not associated similarly due to the absence of hydrogen atoms available for hydrogen-bond formation.

As the ability to form hydrogen bonds decreases from primary to tertiary amines the boiling points of primary, secondary, and tertiary amines of similar molecular weight also decrease in that order.

⇒ CH₃CH₂CH₂NH₂ mol. wt. 59 b.p. 321 K

⇒  CH₃NHCH₂CH₃ b.p. 309 K

Solubility:

Primary, secondary, and tertiary amines with five or fewer carbons are soluble in water as they can form hydrogen bonds with water. The solubility decreases as the hydrophobic alkyl part of the amine increases in size. Amines are soluble in polar solvents like alcohol and ether.

Chemical Properties

The reactivity of amines can be attributed chiefly to the presence of a lone pair of electrons on an electronegative nitrogen. Amines therefore act as nucleophiles.

The basic character of amines

Aliphatic as well as aromatic amines are Lewis bases. The basicity of amines depends upon the readiness with which the lone pair of electrons is available to a proton or to a Lewis acid.

Nitrogen is less electronegative than oxygen, and hence it has a greater tendency to donate its lone pair than does oxygen. Therefore, amines are stronger bases than alcohol, ether or water. However, amines are far weaker bases than hydroxide ions, alkoxide ions, and carbanions.

Relative basicity of amines:

Aliphatic amines (CH₃NH₂, C₂H, NH₂, etc.) are more basic than ammonia because the electron-releasing alkyl groups increase the electron density around the nitrogen, thereby increasing the availability of the lone pair of electrons.

We might expect to see an increase in basic strength on going from NH₃→RNH₂ → R₂NH → R₃N, due to the increasing inductive  effect of successive alkyl groups. The basicity of amines in the gaseous phase follows the expected order

⇒ R₃N>R₂NH>R-NH₂> NH₃

But this order is not observed in the aqueous state as evidenced by their pK, values given in Table.

The pK values of some amines:

The introduction of an alkyl group into ammonia increases the basic strength. The introduction of a second alkyl group further increases the basic strength. However, the introduction of a third alkyl group (as in a tertiary amine) decreases the basic strength.

This is because the basic strength of an amine in an aqueous medium is determined not only by electron availability on the nitrogen atom, but also by the extent to which the cation, formed by the uptake of a proton, can undergo solvation, and so become stabilized. The greater the number of hydrogen atoms attached to nitrogen in the cation, the greater is the possibility of solvation via hydrogen bonding between the cation and water.

Thus on going along the series, NH₃ →R-NH₃→ R₂NH→R₃N, the inductive effect will tend to increase the basicity, but progressively less stabilization of the cation by hydration will occur, which will tend to reduce the basicity.

Therefore, in an aqueous solution, a tertiary amine becomes less basic than a secondary amine. Also, the three alkyl groups around nitrogen in a tertiary amine interfere with protonation, making it less basic. In fact, the basic strength of alkyl amines in an aqueous medium is decided by a combination of the inductive effect, solvation effect, and steric hindrance of the alkyl groups.

The order of basicity of amines changes if the alkyl group is bigger (for example,C₂H₅) than the CH₃ group due to steric hindrance to hydrogen bonding. The order of basic strength of methyl-substituted amines and ethyl-substituted amines in an aqueous medium is as follows.

⇒ (C₂H₅)₂NH)> (C₂H₂)₃N =C₂H₅NH₂>NH₃

⇒ (CH₃)₂NH >CH₃−NH₂ > (CH₃)₃ N > NH₃

Aniline is less basic than methylamine. The low basicity of aniline is due to the delocalization of the lone pair of electrons on nitrogen with the electrons of the benzene ring, making the lone pair of electrons on nitrogen less available for protonation. The delocalization of the lone pair of electrons with the electrons of the benzene ring is shown in the following resonating structures of aniline.

On the other hand, the anilinium ion obtained by the acceptance of a proton is a resonance hybrid of only two structures.

Thus aniline (5 resonating structures) is more stable than the anilinium ion (2 resonating structures) (the greater the number of resonating structures, the greater is the stability). Therefore, the basic nature (or capacity to accept protons) of aniline is less.

Electron-releasing groups like -CH₃,-OH and -OMe in the para position increase the basicity of an aromatic amine, while electron-withdrawing groups like -NO₂,-CHO, and -COOH reduce the basicity.

Ammonium Salt Formation

Since amines are basic they react with mineral acids to form ammonium salts.

The free amine can be obtained from the ammonium salt by treatment with NaOH.

⇒ \(\mathrm{R}-\stackrel{+}{\mathrm{NH}_3} \mathrm{X}^{-} \stackrel{\mathrm{NaOH}}{\longrightarrow} \mathrm{RNH}_2+\mathrm{H}_2 \mathrm{O}+\mathrm{NaX}\)

Ammonium salts are soluble in water and are insoluble in organic solvents (example, ether).

On the basis of the above reactions, we can separate amines from nonbasic organic compounds insoluble in water. Suggest how aniline is separated from acetophenone (a ketone) on the basis of the above reactions.

Alkylation

An alkylamine reacts with an alkyl halide to yield a dialkylamine, a trialkylamine, and a tetraalkylammonium halide (quaternary ammonium salt). For example,

Acylation

Primary and secondary amines react with acyl halides, acid anhydrides, and esters to give substituted amides. This reaction is known as acylation. Tertiary amines do not have a free hydrogen atom and thus do not form amides. The acetylation reaction with acetyl chloride is often carried out in pyridine. Pyridine removes the HCl formed and shifts the equilibrium to the right-hand side.

Mechanism The amine acts as a nucleophile:

Because of the low basicity of amides, they do not readily undergo further acylation by acid chlorides. Amines react with benzoyl chloride (C₆H₅COCI) to form substituted benzamides. The reaction is known as benzoylation.

⇒ RNH₂+C₂₆H₅COCI→ C₆H₅CONHR (Substituted benzamide)+ HCI

Carbylamine Reaction (Carbylamine Test)

Primary amines (aliphatic or aromatic) react with chloroform and ethanolic potassium hydroxide solution to yield isocyanides.

This reaction is often used as a test for the identification of a primary amine.

Secondary and tertiary amines do not undergo this reaction.

Reaction With Grignard Reagent

Primary and secondary amines react with a Grignard reagent to yield an alkane containing the same number of carbons as are present in the alkyl group of the Grignard reagent.

Tertiary amines do not undergo this reaction.

Reaction With Nitrous Acid

The reaction of aliphatic primary amines with nitrous acid (NaNO₂ + HCl) at 273 K yields an unstable alkyl diazonium salt which decomposes to give an alcohol and liberate nitrogen quantitatively. The quantitative evolution of nitrogen is used in the estimation of amino acids and proteins.

⇒ \(\mathrm{R}-\mathrm{NH}_2 \underset{\left(\mathrm{NaNO}_2 / \mathrm{HCl}\right)}{\stackrel{\mathrm{HONO}}{\longrightarrow}}\left(\mathrm{R}-\stackrel{+}{\mathrm{N}_2}\right) \mathrm{Cl}^{-} \stackrel{\mathrm{H}_2 \mathrm{O}}{\longrightarrow} \mathrm{ROH}+\mathrm{N}_2 \uparrow\)

Example 5: Give The Mechanism of the  following reaction

Solution: 

Aromatic primary amines react with NaNO₂/HCl to form stable diazonium salts.

Secondary amines, both aliphatic and aromatic, react with nitrous acid to produce N-nitrosamines, which separate from the reaction mixture as yellow oily liquids.

Nitrosamines are poisonous compounds and are carcinogenic.

Tertiary amines simply dissolve in nitrous acid, forming a salt.

N, N-dimethylaniline an aromatic tertiary amine, reacts with nitrous acid to yield p-nitroso-N, N-dimethylaniline.

In this reaction, the nitroso group is substituted at the p-position of the benzene ring.

Example 6: Suggest a mechanism for the following reaction.

Solution:

Reaction With Aldehydes And Ketones

Primary and secondary amines react with aldehydes and ketones to form a-hydroxylamines, which usually lose water to give a substituted amine, frequently referred to as a Schiff base.

⇒ CH₃CH₂NH₂ +CH₃CHO→ C₂H₅N (Aldimine (Schiff base) =CHCH₃ + H₂O

Aniline condenses with an aldehyde to form an imine or Schiff base with the loss of water. An aromatic amine forms a more stable Schiff base than an aliphatic amine.

⇒  C₆H₅NH₂+C₆H₅CHO→C₆H₅N=CHC₆ H₅ + H₂O

Reaction With Benzene Sulphonyl Chloride

Primary amines react with benzene sulphonyl chloride (Hinsberg reagent) to yield N-alkylbenzene sulphonamide.

⇒ \([\mathrm{R}-\mathrm{NH}_2+\mathrm{C}_6 \mathrm{H}_5 \mathrm{SO}_2 \mathrm{Cl} \rightarrow \underset{\text { N-Alkylbenzenesulphonamide }}{\mathrm{R}-\mathrm{NH}-\mathrm{SO}_2 \mathrm{C}_6 \mathrm{H}_5}\)

N-alkylbenzene sulphonamides have an N-H group, the hydrogen of which is acidic due to the powerful electron-withdrawing sulphonyl group. As a result, N-alkylbenzene sulphonamides are soluble in an excess of a cold NaOH solution.

⇒ \(\mathrm{R}-\mathrm{NH}-\mathrm{SO}_2-\mathrm{C}_6 \mathrm{H}_5+\mathrm{NaOH} \rightarrow \mathrm{R}-\stackrel{\ominus}{\mathrm{N}}-\mathrm{SO}_2-\mathrm{C}_6 \mathrm{H}_5 \stackrel{+}{\mathrm{Na}}+\mathrm{H}_2 \mathrm{O}\)

Secondary amines react with benzenesulphonyl chloride to yield N, N dialkylbenzenesulphonamide, which does not dissolve in an NaOH solution.

Tertiary amines do not react with benzene sulphonyl chloride.

These reactions are used to distinguish between primary, secondary and tertiary amines, and to separate them. The test is known as the Hinsberg test.

Hinsberg test:

• To differentiate primary, secondary, and tertiary amines, the unknown amine is shaken in a test tube with benzene sulphonyl chloride and dilute sodium hydroxide solution. A primary amine is present if a clear solution is obtained.
• If an insoluble layer remains, it can be either due to a secondary or tertiary amine, because a secondary amine forms an insoluble sulphonamide whereas a tertiary amine does not react.
• These two can be distinguished by acidifying the mixture with dilute HCl. If the layer disappears it is a tertiary amine because it will form a water-soluble salt.
• However, the separation of an insoluble compound, a neutral sulphonamide, indicates the presence of a secondary amine.

Separation of primary, secondary, and tertiary amines-Hinsberg method:

• The mixture of amines is treated with aqueous KOH followed by benzene sulphonyl chloride (or p-toluene sulphonyl chloride).
• Primary amines form benzenesulfonamide (soluble in alkalis); the secondary amines also form benzenesulfonamide (but insoluble in alkalis); the tertiary amines remain unaffected.
• The mixture is warmed in a water bath to complete the reaction. The alkaline mixture is acidified with dilute HCI, whereby sulphonamides of primary and secondary amines are precipitated. The solid is filtered and washed with a little cold water. The tertiary amine remains in the filtrate.
• The solid is then boiled with aqueous KOH. The alkali-insoluble sulphonamide of the secondary amine is filtered off. The filtrate is acidified with dilute HCl to precipitate the sulphonamides of the primary amine.
• On boiling the sulphonamides of the primary and secondary amine with 80% H₂SO₄, and rendering them alkaline with aqueous KOH, the original primary and secondary amines may be recovered.

Electrophilic Substitution Reactions Of An Aromatic Amine (Aniline)

The amino group in aromatic amines is a powerful activating group and is ortho-para directing. This is due to the delocalization of the lone pair of electrons of nitrogen with the electrons of the benzene ring, as shown

The maximum electron density occurs at the o- and p-positions. Aromatic amines, therefore, undergo typical electrophilic substitution reactions rapidly. In some cases, the rate of the reaction is so great that the poly-substituted product is formed even in mild conditions. In order to prepare a monosubstituted product, the activating influence of the -NH₂ group is moderated by introducing an acetyl group.

Halogenation

Halogenation of aniline takes place readily at room temperature and does not require the presence of a catalyst. For example, aniline, when treated with bromine water, gives 2, 4, and 6-tribromoaniline.

2, 4, 6-tribromoaniline is formed readily because aniline is extremely susceptible to electrophilic substitution. The substitution tends to occur readily at the ortho and para positions. In order to prepare a monosubstituted aniline, the activating effect of the NH₂ group has to be controlled.

This is usually done by protecting the NH₂ group by acetylation with acetic anhydride to get acetanilide. This electrophilic substitution with Br₂ in acetic acid gives p-bromoacetanilide. On hydrolysis, this yields p-bromoaniline.

In acetanilide, the lone pair of electrons on nitrogen is attracted toward the strong electron-attracting carbonyl group due to resonance.

Thus, the lone pair of electrons on nitrogen becomes less available for delocalisation with the electrons of the benzene ring. The reactivity of the NHCOCH, group is thus reduced as compared to that of the -NH₂ group.

Nitration

Aniline is susceptible to oxidation and a lot of it is decomposed as tarry material when made to react with concentrated HNO₃. On treatment with concentrated HNO₃ and concentrated H₂SO₄, aniline forms the anilinium cation (CH-NH₃) by accepting a proton (H*). The anilinium ion is m-directing. Therefore, the product obtained is mainly m-nitroaniline, together with o- and p-nitroaniline.

Monosubstituted p-nitroaniline may be obtained according to the following set of reactions. Aniline is first acylated to prepare acetanilide. Acetanilide on nitration (concentrated HNO₃ + concentrated H₂SO₄) gives p-nitroacetanilide, which on hydrolysis yields p-nitroaniline.

Sulphonation

Aniline reacts with concentrated H₂SO₄ to give anilinium hydrogen sulfate. The salt on heating with concentrated H₂SO₄, to 453 K forms sulphanilic acid (p-amino benzene sulphonic acid).

Since sulphanilic acid contains both an acidic group (-SO₃H) and a basic group (-NH₂) in the same molecule, an ‘inner-salt’ is formed as a zwitterion or dipolar ion. Aniline does not respond to Friedel-Crafts alkylation and acetylation reactions because it forms a salt with AICI₃ (Lewis acid) used as a catalyst.

⇒  C₆H₅NH₂ + AlCl₃ → C₆H₅N⁺H₂ AICI^–₂

Due to this, the nitrogen of aniline becomes positively charged and deactivates the ring. Deactivated compounds usually do not undergo Friedel-Crafts reaction.

Benzenediazonium Salts

The term diazonium is derived from the Greek word azote (nitrogen). A benzenediazonium salt has the general formula \(\mathrm{C}_6 \mathrm{H}_5-\stackrel{+}{\mathrm{N}} \equiv \mathrm{N} \bar{X}\)where X may be Cl^–, Br^–, NO₃^–, or HSO₄^–. The group N = N- is called the azo group.

The prefix azo is used when both nitrogen atoms (-N-N-) are attached to carbon. When one is attached to carbon and one to some other atom, the suffix diazo is used. While naming these compounds, the suffix diazonium is added to the name of the aromatic hydrocarbon and then the name of the anion is written as a separate word.

Aromatic amines form aromatic diazonium salts. These are more stable than alkyl diazonium salts. The greater stability of the aromatic diazonium ion is due to resonance.

Preparation

Aniline is dissolved or suspended in a mineral acid (HCI) and cooled to 0°C. Then a cold solution of sodium nitrite is added slowly in slight excess.

⇒ \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{NH}_2+\mathrm{HCl} \rightarrow \mathrm{C}_6 \mathrm{H}_5 \mathrm{NH}_2 \cdot \mathrm{HCl}\)

⇒ \(\mathrm{NaNO}_2+\mathrm{HCl} \rightarrow \mathrm{HNO}_2+\mathrm{NaCl}\)

⇒ \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{NH}_2 \cdot \mathrm{HCl}+\mathrm{HNO}_2 \rightarrow \underset{\begin{array}{c}
\text { Benzenediazonium } \\
\text { chloride }
\end{array}}{\mathrm{C}_6 \mathrm{H}_5 \mathrm{~N}_2 \mathrm{Cl}}+2 \mathrm{H}_2 \mathrm{O}\)

The process of converting aromatic primary amines to diazonium salts by the action of nitrous acid is known as diazotization.

Physical Properties

Benzenediazonium chloride is a colourless crystalline solid and is readily soluble in water. Aqueous solutions of benzene diazonium chloride are not stable. Nitrogen gas is evolved slowly in cold conditions and rapidly on warming this compound. This compound is relatively stable below 273 K. Bezenediazonium fluoroborate is stable, and can be dried and stored.

Chemical Reactions

Benzene diazonium salts are highly reactive compounds that serve as intermediates in the synthesis of a wide variety of aromatic compounds. The reactions of benzene diazonium salts may be divided into the following two categories.

1. Substitution of the diazonium group, and
2. Coupling reactions.

1. Substitution of the diazonium group

By Cl^–, Br^– and CN^– When a diazonium salt solution is treated with hydrogen chloride, bromide, or cyanide in the presence of the corresponding cuprous halide or the cyanide as catalyst, the diazo group is replaced by the halide group or cyanide group. This is known as the Sandmeyer reaction.

In another reaction, when a diazonium salt solution is treated with hydrogen chloride, bromide or cyanide in the presence of copper powder, the diazo group is replaced by the halide group or the cyanide group. This is known as the Gattermann reaction.

The yield of the halobenzene or cyanobenzene is greater in the Sandmeyer reaction than in the Gattermann reaction.

By iodine:

lodine cannot substitute the diazonium group in the benzene ring by halogenation. Therefore, iodobenzene is prepared by making benzene diazonium chloride react with potassium iodide.

By fluorine:

Aqueous fluoroboric acid, HBF₄ reacts with a benzenediazonium salt to yield C₆H₅N₂^– BF₄^–, On gentle heating in the absence of a solvent, the latter decomposes to give fluorobenzene.

By NO₂ group:

On being heated with sodium nitrite in the presence of copper powder, benzene diazonium fluoroborate yields nitrobenzene.

By OH group:

At 283 K, an aqueous solution of benzenediazonium chloride yields phenol.

By hydrogen:

Benzene diazonium chloride is reduced by hypophosphorous acid (H₃ PO₂) to benzene.

In all the above reactions, nitrogen is displaced from the aromatic ring and escapes as a gas.

Summary of the syntheses using diazonium salts:

2. Coupling reactions

When diazonium salts are treated with phenols or aromatic amines in a basic medium, azo compounds (azo compounds contain the group-N-N-) are formed. These are known as coupling reactions.

These reactions are a kind of electrophilic aromatic substitution in which aromatic diazonium ions act as poor electrophiles. They attack a benzene ring that has an activating group on the ring.

The coupling takes place para to the OH or -NR₂ group unless this position is blocked. The azo compounds are usually colored (orange, red, or yellow). The double-bonded nitrogen atoms are largely responsible for giving the azobenzenes their colors. A group like -NN-is called a chromophore.

The last coupling reaction described above is used in the detection of primary aromatic amines. Aromatic amines on diazotization give diazonium salts which on treatment with β-naphthol form a red/orange dye. The formation of a red/orange dye confirms the presence of an aromatic amino group.

When a benzene diazonium ion reacts with aniline, a somewhat different reaction takes place. Instead of attacking the ring, the ion bonds to the nitrogen atom of aniline, and a yellow solid is obtained.

Diazoaminobenzene reacts with excess aniline and acid to give the aromatic substitution product, p-aminoazobenzene.

Amines Multiple-Choice Questions

Question 1. Which of the following is the functional group of a primary amine?

1. —NH–
2. -NH₂
3. ⁺NH₃
4. NH₃

Answer: 2. -NH₂

Question 2. Amines are derivatives of

1. CO₂
2. Urea
3. NH₃
4. None of these

Answer: 3. NH₃

Question 3. Which of the following is formed when ethylamine reacts with nitrous acid?

1. C₂H₂OH
2. CH₃COOH
3. C₂H₂NO₂
4. None of these

Answer: 1. C₂H₂OH

Question 4. Which of the following is formed when methylamine is heated with chloroform and alcoholic KOH?

1. CH₃NC
2. CH₂CN
3. CH₃CHO
4. CH₃OH

Answer: 1. CH₃NC

Question 5. A Grignard reagent reacts with a primary amine to produce

1. An alkane
2. Tertiary amine
3. None of these
4. A secondary amine

Answer:  1. An alkane

Question 6. The reduction of nitroalkane gives a

1. Secondary amine
2. Primary amine
3. A higher amine
4. Quaternary salt

Answer: 3. A higher amine

Question 7. Which of the following is formed when acetamide reacts with Br₂/NaOH?

1. Acetone
2. Methylamine
3. Ammonia
4. Acetaldehyde

Answer:  2. Methylamine

Question 8. Which of the following is formed when aniline reacts with fuming sulphuric acid?

1. Sulphonic acid
2. Sulphanilic acid
3. Benzene sulphonic acid
4. Benzoic acid.

Answer: 2. Sulphanilic acid

Question 9. Which of the following is formed when aniline is heated with chloroform and alcoholic KOH?

1. Chlorobenzene
2. p-Hydroxyaniline
3. Carbylamine
4. Acetanilide

Answer: 3. Carbylamine

Question 10. What is the hybridization state of N in an amine?

1. Sp³
2. Sp²
3. Sp
4. Sp³d

Answer: 1. Sp³

Question 11. Among the following, which is the correct order of basic strength?

1. NH>CH₃NH₂> NF₃
2. CH₃NH₂>NH₃>NF₃
3. NF₃> CH₃NH₂> NH₃
4. NH₃> NF₃> CH₃NH₂

Answer: 2. CH₃NH₂>NH₃>NF₃

Question 12. Which of the following is the most basic?

1. C₆H₅NH₂
2. (CH₃)₂> NH
3. (CH₃)₃N
4. NH₃

Answer:  2. (CH₃)₂> NH

Question 13. Which of the following is the order of basic strength of amines in a benzene solution?

1. CH₃NH₂> (CH₃)₃N> (CH₃)₂NH
2. (CH₃)₃N> (CH₃)2NH> CH₃NH₂
3. CH₃NH₂> (CH₃)2NH> (CH₃)₃N
4. (CH₃)₃N> CH₃NH₂>(CH₃)₂NH

Answer: 2. (CH₃)₃N> (CH₃)2NH> CH₃NH₂

Question 14. Which of the following is the most reactive towards electrophilic substitution?

1. Nitrobenzene
2. Aniline
3. Aniline hydrochloride
4. N-Acetylaniline

Answer: 2.  Aniline

Question 15. Which of the following is the most basic?

1. C₆H₅NH₂
2. p-NO₂-C₆H₄NH₂
3. m-NO₂-C₆H₄NH₂
4. C₆H₅CH₂NH₂

Answer: 4. m-NO-CH₄NH₂

Question 16. What are the products formed when aniline is heated with concentrated HNO, and concentrated H₂SO₄?

1. o- and p-Nitroaniline
2. p-Nitroaniline
3. Tarry material
4. There is no reaction.

Answer: 3. Tarry material

Question 17. The reaction of a primary amine with chloroform and ethanolic KOH is called the

1. Carbylamine reaction
2. Kolbe reaction
3. Reimer-Tiemann reaction
4. None of these

Answer: 1. Carbylamine reaction

Question 18. Benzene diazonium chloride reacts with phenol in a weak basic medium to give

1. Diphenyl ether
2. p-hydroxy azobenzene
3. Chlorobenzene
4. Benzene

Answer: 2. p-hydroxy azobenzene

Question 19. Which of the following does not react with acetyl chloride?

1. Methylamine
2.  Ethylamine
3. Dimethylamine
4. Trimethylamine

Answer: 3. Dimethylamine

Question 20. Hinsberg reagent is

1.  Benzene sulphonic acid
2. Benzenesulphonamide
3.  p-Toluenesulphonyl chloride
4.  None of these

Answer: 3.  p-Toluenesulphonyl chloride

Question 21. How many primary amines have the molecular formula C₄H₁₁N?

1. 1
2. 2
3. 3
4. 4

Answer: 4. 4

Question 22. In reaction with aqueous HNO₂ at low temperatures, a compound produces an oily nitrosamine. The compound is likely to be

1. Methylamine
2. Ethylamine
3. Diethylamine
4. Triethylamine

Answer: 3. Diethylamine

Question 23. An amine reacts with benzenesulphonyl chloride and the product is insoluble in NaOH. The amine is likely to be

1. A primary amine
2. A secondary amine
3. A tertiary amine
4. All of these

Answer: 2. A secondary amine

Question 24. Which of the following compounds is the least basic? a secondary amine

Answer: 3

Question 25. What is the correct order of basicity of the following compounds?

1. (2)>(1)>(3) > (4)
2. (3)> (1)>(2) > (4)
3. (1)>(3)>(2)>(4)
4. (1)>(2)>(3)>(4)

Answer: 3. (1)>(3)>(2)>(4)

Polymers

Many things of everyday use are made of polymers. For example, fabric for clothing and furniture, plastic utensils, containers, toys, toothbrushes, synthetic rubber for automobile tyres, paints and varnishes, paper and pens.

• Large molecules (macromolecules) formed by a series of chemical reactions between small molecules are called polymers; the word is derived from the Greek polymers meaning “many parts” (poly = many, meros = parts).
• The small molecules that make up the giant polymer are called monomers, meaning “of one part”. The formation of large molecules by the linking together of small molecules is called polymerisation.
• The structural formulae of some common polymers, along with the monomers from which they are made, are given below.

• Polymers made up of a few monomers are called oligomers. An example is crystalline sulphur, a molecule of which has eight sulphur atoms arranged in a ring. As is obvious, the monomeric unit is a sulphur atom.
• – OH
• The properties of polymers are related to molecular mass, size and structure. The molecular mass of a polymer depends on the conditions of polymerisation.
• The length of the polymer chain depends upon the availability of monomer molecules in the reaction mixture. Thus, a polymer contains chains of varying lengths.
• Therefore the molecular mass of a polymer is expressed as an average.

Polymers Classification

Polymers May Be Classified In Several Ways.

On the basis of the type of chain

Polymers may be made up of three types of chains-linear, branched and crosslinked.

1. Linear-chain polymers:

High-density polymers with long straight chains are called linear-chain polymers. Examples are polyethene and polyvinyl chloride. The chains in such a polymer may be depicted as follows.

2. Branched-chain polymers:

Low-density polymers having linear chains with some branches are called branched-chain polymers. An example of such a polymer is polypropylene. The chains in a branched-chain polymer may be shown as follows.

3. Crosslinked polymers:

Crosslinked polymers contain strong covalent bonds between various linear chains. Examples of such polymers are bakelite and melamine. The chains in the polymer may be depicted. The monomers in a crosslinked polymer generally have two or three functional groups.

On The Basis Of Intermolecular Force

Polymers are known for their special mechanical properties such as toughness, elasticity and tensile strength. The degree of toughness, elasticity and so on depends upon the intermolecular forces in the large polymer molecules.

These forces may be van der Waals forces, forces due to hydrogen bonds, etc. Such forces are present in smaller molecules too but their effect is not so pronounced. The larger the molecule, the greater is the effect.

Polymers may be divided into four groups based on the strength of their intermolecular forces—

1. Thermoplastics,
2. Thermosetting Polymers,
3. Elastomers And
4. Fibres.

Thermoplastics

• As you know, a polymer may be linear, branched or crosslinked. The first two types of polymers are said to be thermoplastic as they can be moulded into different shapes, after being heated and then cooled.
• They soften on heating and harden on cooling. They also dissolve in the appropriate solvents.. These polymers possess an intermolecular force of attraction that is between those of elastomers and fibres.
• Common examples of thermoplastics are polythene, polystyrene and polyvinyl chloride.

Thermosetting polymers

• A crosslinked polymer, i.e., one in which the monomer chain is crosslinked to other adjacent chains to form a three-dimensional network, is a thermosetting polymer. It is less soluble in solvents than a thermoplastic is.
• It hardens on heating and can be moulded only once because it becomes rigid and heat cannot soften it for remoulding. Examples of thermosetting polymers are bakelite and urea-formaldehyde resins.

Elastomers

• Polymers with elastic qualities are known as elastomers. In these polymers, each chain is held together by weak van der Waals forces of attraction. Among the polymers, the binding force is the weakest in elastomers.
• These weak forces allow the polymer to be stretched. Elastomers also contain a few short chains of sulphur atoms, which serve as linkages between the polymer chains.
• The sulphur chains help align the polymer chains, so the material does not undergo a permanent change when stretched, but springs back to its original shape and size when the stress is removed.
• Vulcanised rubber is a common example of an elastomer. Other examples are buna-S, buna-N and neoprene.

Stretched vulcanised rubber retains its elasticity.

Fibres

• Synthetic fibres are thread forming semicrystalline solids which possess high tensile strength and high modulus of elasticity.
• In order to have a high tensile strength, the chains of atoms in a polymer should be able to attract one another, but not so strongly that the plastic cannot be initially extended to form the fibres.
• Ordinary covalent bonds would be too strong. Hydrogen bonds, with a strength of about one-tenth that of ordinary covalent bonds, link the chains in the desired manner.
• Examples of fibres are polyamides [nylon 6, 6, nylon 6 and polyesters (Terylene)].

On The Basis Of Their Sources

On the basis of their sources, polymers are classified as natural, semi-synthetic and synthetic.

Natural polymers

• Plants produce an enormous number of molecules, which vary in size, shape and function. Some of them, such as cellulose, starch and rubber, are large polymers.
• The polymer cellulose is a constituent of cotton, wood and the cell walls of plants. It is a condensation polymer whose monomer unit is the molecule β-glucose.

• Another natural polymer is starch. It is a constituent of many plants, including potatoes, wheat, rye, oats, corn and rice. The a-glucose molecule is the monomer unit for this polymer.
• This molecule differs from that of B-glucose only in respect of the relative position of the OH group bonded to Cl. In a-glucose, this -OH group is pointed towards the bottom of the ring; in γ-glucose, it is pointed towards the top.

The structures of cellulose and starch

Another naturally occurring polymer is rubber. The name rubber was given to this substance when it was found to rub out pencil marks. Rubber is formed from the monomer isoprene, C₅H₈ and is also called cis-polyisoprene.

Where n = 11, 000 to 20,000

The structure may be represented as

The cis structure of natural rubber is vital to its elasticity.

Gutta-percha is a naturally occurring isomer of rubber in which all the -CH₂-CH₂-groups are trans.

• Poly trans isoprene (the-CH₂-CH₂– groups are trans)
• The trans compound is hard and brittle.
• Rubber is extracted from trees. It occurs as latex (a suspension of rubber particles in water) that oozes from rubber trees when their trunks are slit.
• On treatment with 1% acetic acid, the rubber particles are precipitated from the latex as a gummy mass. The gummy mass is not only elastic and water-repellent but also very sticky, especially when warm.
• In 1839, Charles Goodyear discovered that heating latex with sulphur produces a material (vulcanised rubber) that is no longer sticky, but still elastic and water-repellent.
• Vulcanised rubber contains short chains of sulphur atoms which bind the polymer chains of natural rubber. It is an elastomer, and its structure may be represented.

The composition of a car tyre:

Semisynthetic polymers

• Cellulose was the first polymer to be chemically modified to new substances useful to human beings. When made to react with acetic anhydride in acetic acid using a little sulphuric acid as a catalyst, cellulose is converted into its acetate.
• When a solution of cellulose triacetate is forced through small holes into a solution of dilute acetic acid, the water precipitates it in the form of a continuous thread that can be used to weave fabrics.
• The use of cellulose in a variety of other products is based on similar modifications of structure. For example, the hydroxyl groups in cellulose are converted into alkoxide anions by a base. These anions add to CS₂ to give compounds known as xanthate esters.
• The basic solution of cellulose xanthate salts can be forced out of spinners into dilute H₂SO₄ to form rayon threads. If thin slits are used, sheets of cellophane are formed. Both rayon and cellophane are essentially cellulose in a transformed physical state.

Synthetic polymers

These are polymers synthesised in the laboratory or in manufacturing units and may be obtained by two processes polymerisation or chain-growth polymerisation and condensation polymerisation or step-growth polymerisation.

Addition polymerisation:

• Addition polymerisation generally occurs between molecules containing one or more double bonds. No small molecules are liberated during this process.
• A very important group of olefinic compounds that undergoes addition polymerisation is of the type CH₂=CH-Y, where Y may be H, X, COOR, CN, etc.

⇒\(n \mathrm{CH}_2=\mathrm{CH}-\mathrm{Y} \longrightarrow\left(\mathrm{CH}_2-\mathrm{CH}-\mathrm{Y}\right)_n\)

Polymerisation Mechanism:

Alkenes and their derivatives polymerise by the free-radical mechanism in the presence of organic peroxides such as benzoyl peroxide, acetyl peroxide and t-butyl peroxide.

• For example, ethylene polymerises under high pressure (1000 atm) at an elevated temperature (473 K). The reaction is initiated by a free radical (catalyst) produced by organic peroxides, for example benzoyl peroxide, acetyl peroxide, and t-butyl peroxide.
• The polymerisation of ethylene, initiated by dibenzoyl peroxide, is a radical chain reaction. The peroxide is first cleaved homolytically to give two benzoate radicals, which produce the phenyl radical. The phenyl radical adds to the alkene to give an unstable primary carbon radical.
• This step is called the chain-initiating step. The primary carbon radical adds to another molecule of the alkene, and so on. This step is termed as the chain-propagating step. Finally, the chain is terminated by combination with another radical (the chain-terminating step).

The following steps are involved.

1. Chain Initiation:

2. Chain Propagation:

⇒ \(\mathrm{C}_6 \mathrm{H}_5 \mathrm{CH}_2 \dot{\mathrm{C}} \mathrm{H}_2+\mathrm{CH}_2=\mathrm{CH}_2 \rightarrow \mathrm{C}_6 \mathrm{H}_5 \mathrm{CH}_2 \mathrm{CH}_2 \mathrm{CH}_2 \dot{\mathrm{C}} \mathrm{H}_2 \rightarrow \mathrm{C}_6 \mathrm{H}_5\left(\mathrm{CH}_2-\mathrm{CH}_2-\mathrm{CH}_2-\dot{\mathrm{C}} \mathrm{H}_2\right.\)

3. Chain Termination:

Anionic and cationic polymerisations also take place, but they are not as common as the free radical processes. Ionic polymerisations are usually very fast and exothermic.

Example 1. Give the mechanism for the formation of a segment of polyvinyl chloride containing three units of vinyl chloride initiated by HO.

Solution:

Addition polymers:

Polymers synthesised by addition polymerisation are called addition polymers. A polymer made of only one type of monomer is known as a homopolymer. A polymer made of more than one type of monomer is known as a copolymer.

Polyethylene or polyethene: There are two varieties of polythene-

1. Low-density polyethene (Ldp) And
2. High-density polythene (Hdp).

1. Low-density polythene:

Low-density polythene is produced at high temperatures (473 K) and high pressure (≈ 1000 to 2000 atmospheres) using oxygen or peroxide as the initiator (catalyst). Under these circumstances, free radicals attack the chain at random positions, thus causing irregular branching.

• The polythene with irregular branching is less dense and more flexible since the molecules are generally far apart and their arrangement is not so precisely ordered. this material is used for making squeeze bottles toys and flexible pipes , among other things

⇒ \(\underset{\text { Ethylene }}{n\left(\mathrm{CH}_2=\mathrm{CH}_2\right)} \underset{473 \mathrm{~K}}{\stackrel{\mathrm{O}_2}{\longrightarrow}}+\underset{\text { Polythene }}{\left.\mathrm{CH}_2-\mathrm{CH}_2-\right)_n}\)

2. High-density polythene:

High-density polyethene is produced at low temperatures (333 K To 343K) and comparatively low pressure(6-7atmospheres) in the presence of a catalyst (C₂H₂)₃ Al/TiCl₄ (Ziegler-Natta catalyst).

• This catalyst yields almost exclusively linear polythene. The molecules in linear polythene are strongly attracted to one another by van der Waals forces, yielding a tough, high-density compound due to close packing, which is useful in making toys, bottles and buckets.

Polythenes formed under different pressures and catalytic conditions have different molecular structures and hence different physical properties.

Polypropylene:

Polypropylene was prepared for the first time by the Italian chemist Natta in 1960, an achievement for which he was awarded the Nobel Prize in 1963.

He prepared polypropylene by dissolving propylene in the inert solvent heptane containing triethylaluminium and titanium chloride catalyst at a high temperature (373 K) under a pressure of 10 atm.

Polypropene is a substitute for polythene. It is lighter and stronger than the latter. Its softening point is relatively high, and it is used for making hard fibres because it has a high tensile strength.

These fibres are used for making carpets and ropes. Polypropene is also used to make bottles, glasses, pens, toys, electrical goods and pipes.

Polystyrene:

Polystyrene On polymerisation in the presence of dibenzoyl peroxide (catalyst), styrene yields polystyrene.

Styrene itself is prepared from benzene by the following method.

Polystyrene is a transparent polymer and is used in manufacturing food containers, bottles, plastic cups, combs, toys and television cabinets.

Teflon:

Teflon is prepared by heating tetrafluoroethene under high pressure in the presence of ammonium peroxy sulphate.

Teflon is incombustible and is not affected by acids or alkalis. It is used for making insulating material, bearings and nonstick utensils.

Polyvinyl chloride (PVC):

Polyvinyl chloride is obtained by heating vinyl chloride in the presence of benzoyl peroxide in an inert solvent.

Vinyl chloride itself is obtained by the reaction of ethyne (acetylene) with HCl in the presence of HgCl₂ catalyst.

PVC is used in making pipes, plastic syringes, hard plastic bottles, raincoats, shoes, curtains and garden hoses.

Polyacrylonitrile (orlon):

Orlon is prepared by the polymerisation of acrylonitrile (vinyl cyanide) in the presence of FeSO₂/H₂O₂

Orlon is water-resistant and is used in making carpets and blankets.

Polymethyl methacrylate (PMMA):

It is prepared by the polymerisation of methyl methacrylate in the presence of benzoyl peroxide (catalyst).

It is tough and transparent, and is popularly known as plexiglass. It finds use in the manufacture of aeroplane windows, contact lenses, automobile tail lights and in plastic surgery.

Neoprene:

Neoprene, a synthetic rubber, is a polymer of chloroprene (2-chloro-1, 3-butadiene).

Chloroprene:

Chloroprene itself is prepared from ethyne (acetylene).

Neoprene is more resistant than natural rubber to oils and solvents. It is tougher and wears better than rubber. It is used mostly in applications where its toughness and resistance to oil and grease are important, such as in gaskets, sealing rings, and engine mountings. It is also used in making automobile tyres.

Example 2: Draw the structures of the monomers used to synthesise the following polymers.

Solution:

Buna-N-rubber:

 The polymerisation of butadiene in the presence of sodium gives a polymer known as buna-N- rubber. It was the first synthetic rubber to be manufactured. However, it is not very useful.

All the addition polymers described above are homopolymers—they contain the same type of monomer units.

Copolymerisation

• If two or more monomers polymerise to give a single polymer containing different subunits, the product is a copolymer and the process is called copolymerisation.
• The copolymer can be made by addition polymerisation (chain-growth polymerisation) and condensation polymerisation (step-growth polymerisation).
• A copolymer can have useful properties that are different from and often superior to those of a homopolymer. Buna-S-rubber is an example of a copolymer.

Buna-S-rubber:

 Buna-S-rubber is a copolymer prepared by the polymerisation of three moles of butadiene and one mole of styrene. This polymer is tough and possesses properties close to those of natural rubber.

The double bonds in the chain allow this polymer to undergo vulcanisation like a natural rubber polymer chain.

Buna-S-rubber is manufactured on a large scale and used to make automobile and truck tyres. A pure form this polymer is used as a replacement for the latex in chewing gum.

All synthetic rubbers can be vulcanised and can be stretched to twice their length. Once the external force is removed, they return to their initial size and shape.

Condensation polymers:

Condensation polymers are formed when bifunctional monomer molecules are linked. This happens when the monomer molecules react, and a small molecule such as that of water, HCl or alcohol is released. Polyesters and polyamides are examples of condensation polymers.

Polyester:

A typical polyester is prepared by heating a alcohol (ethylene glycol) and a diacid (terephthalic acid) in the presence of a catalyst.

Terephthalic acid (containing two carboxylic acid groups) and ethylene glycol (containing two alcohol groups) can react at both ends.

The reaction of one carboxylic acid group of terephthalic acid with one alcohol group of ethylene glycol initially produces an ester molecule with an acid group at one end and an alcohol group at the other.

Subsequently, the remaining acid group can react with another alcohol group, and the alcohol group can react with another acid molecule. The process continues until an extremely large polymer molecule, known as a polyester, is produced with a molecular weight in the range of 10,000-20,000.

This condensation polymerisation is also called step-growth polymerisation since each step produces a distinct functionalised species.

Polyester can be spun into a fibre from the melt. The fibre is used in making textile fibres marketed under the names Dacron and Terylene. The blending of polyester with cotton provides a fabric with high durability and anticrease properties.

Polyamides (nylons):

Polyamides Many nylons have been prepared and tried in the consumer market. Two of them  nylon 6, 6 and nylon 6-have been the most successful.

Nylon 6, 6 is prepared by the reaction of equimolecular quantities of hexamethylenediamine and adipic acid under high pressure and at high temperatures. The resultant melt is spun into fibre.

The polymer is made up of alternating —NH(CH₂)₆ NH- and -(C₂) 4 4O— units, each having six carbon atoms, and is called nylon 6, 6.

Nylon 6 is prepared by heating caprolactum with water at a high temperature.

This caprolactum monomer is a cyclic amide and the polymer does not have alternating units—each unit is the same containing six carbon atoms and is called nylon 6.

Caprolactum itself is synthesised from cyclohexanone in the following manner.

Nylons have been widely accepted as textile fibres because they are strong, have desirable elastic properties, and can be drawn into very fine fibres. They are used to prepare fishing nets, ropes and brushes, among other things.

Example 3: Identify the monomer units used to make the following polymers.

Solution:

Example 4:  What is the significance of the numbers 6, 6 and 6 in nylon 6, 6 and nylon 6?

Solution:

• The numbers 6, 6 in the name of nylon 6, 6 refer to the six carbon atoms of hexamethylenediamine and the six carbon atoms of adipic acid.
• The number 6 in nylon 6 indicates that six carbon atoms are contributed by the reactant caprolactum.

Glyptal:

Glyptal is prepared by the reaction of ethylene glycol with phthalic acid. It is used to prepare paints and lacquers.

Bakelite or phenol-formaldehyde plastic:

Bakelite is obtained by condensing phenol with formaldehyde under either acidic or basic conditions. Under acidic conditions, polymerisation proceeds to give a three-dimensional network of phenol rings held together at the ortho- and para-positions by methylene groups.

Bakelite is a stiff material with little solubility in organic solvents and a high resistance to electricity and heat. It is used to make a variety of household objects and electrical fixtures. The polymer has the useful property of being thermosetting.

The reaction of phenol with formaldehyde also produces o-hydroxymethylphenol which further reacts with phenol to give a linear product-novolac-used in paints. On being heated with formaldehyde, novolac undergoes cross-linking to form bakelite.

Urea-formaldehyde plastic:

On being heated with formaldehyde in the presence of a dilute acid, urea gives urea-formaldehyde plastic. This plastic is colourless and does not fade in sunlight. It is used to make household materials and kitchenware. Formica, used to cover the surfaces of furniture, cupboards, and so on, is also prepared from urea-formaldehyde plastic. In the form of an ion-exchange resin, urea-formaldehyde plastic is used to purify water.

Melamine-formaldehyde plastic:

Melmac, a polymer used in the manufacture of unbreakable kitchenware, is made by the condensation polymerisation of melamine and formaldehyde.

Melamine itself is produced by the trimerisation of cyanamide (NH₂)—CN).

Hard plastics are made softer by mixing them with a plasticizer. Di-isooctylphthalate is generally used as a plasticizer.

Biodegradable Polymers

Plastics are not very easily degraded and cause environmental problems such as soil pollution. In view of the current global concern for the environment, researchers have been attempting to come up with biodegradable polymers.

In recent years, synthetic polymers have been produced that have built-in susceptibility to bacteria or fungi. The functional groups of the polymers are similar to those of biopolymers.

Aliphatic polyesters and polyamides are important biodegradable polymers.

Poly (B-hydroxybutyrate-ß-hydroxy valerate), PHBV

It is a biodegradable copolymer obtained by the reaction of B-hydroxybutyric acid with β-hydroxyvaleric acid.

Nylon 2-nylon 6:

This a biodegradable copolymer obtained by the reaction of glycine with 6 aminohexanoic acid.

This polymer is made up of alternating -NH-CH₂)-C- and -NH(CH₂)₂)₅ C— units having two carbon atoms and six carbon atoms respectively, and is called nylon 2-nylon 6.

Polymers Multiple-Choice Questions

Question 1. Natural rubber is a polymer of

1. Ethylene
2. Benzene
3. Isoprene
4. None Of These

Answer: 3. Isoprene

Question 2. The polymerisation of which of the following leads to the formation of neoprene rubber?

1. Chloroprene
2. Isoprene
3. 1,3-Butadiene
4. Acetylene

Answer: 1. Chloroprene

Question 3. Which of the following is a natural polymer?

1. Protein
2. Polythene
3. Buna-S
4. Bakelite

Answer: 1. Protein

Question 4. Which of the following contains ester linkages?

1. Terylene
2. Nylon
3. Teflon
4. Bakelite

Answer: 1. Terylene

Question 5. Which of the following is obtained by the condensation of adipic acid and hexamethylene diamine?

1. Rayon
2. Terylene
3. Nylon 6, 6
4. Carbon Fibre

Answer: 3. Nylon 6, 6

Question 6. Teflon, polystyrene and neoprene are

1. Copolymers
2. Condensation Polymers
3. Homopolymers
4. Monomers

Answer: 3. Homopolymers

Question 7. Which of the following contains an amide linkage?

1. Nylon 6, 6
2. Terylene
3. Teflon
4. Bakelite

Answer: 1. Nylon 6, 6

Question 8. Phenol is used in the formation of which of the following?

1. Bakelite
2. Polystyrene
3. Nylon
4. PVC

Answer: 1. Bakelite

Question 9. In the Ziegler method, which of the following catalysts is used in the formation of polythene?

1. Lithium Tetrachloride And Triphenylaluminium
2. Titanium Tetrachloride And Triethylaluminium
3. Titanium Oxide
4. Titanium Isoperoxide

Answer: 2. Titanium Tetrachloride And Triethylaluminium

Question 10. PMMA is a polymer of which of the following?

1. Methyl Methacrylate
2. Methyl acrylate
3. Ethyl acrylate
4. All Of These

Answer: 1. Methyl Methacrylate

Question 11. Orlon is a polymer of which of the following?

1. Tetrafluoroethylene
2. Acrylonitrile
3. Ethanoic acid
4. Benzene

Answer: 2. Acrylonitrile

Question 12. Natural rubber is a polymer of which of the following?

1. Trans-Isoprene
2. Cis-Isoprene
3. Co-Cis- And Trans Isoprene
4. None Of These

Answer: 2. Cis-Isoprene

Question 13. Which of the following is used in making nonstick cookware?

1. Polystyrene
2. Polytetrafluoroethene
3. Polythene
4. None Of These

Answer: 2. Polytetrafluoroethene

Question 14. Which of the following is an example of a copolymer?

1. Nylon 6
2. Nylon 6, 6
3. PMMA
4. Polythene

Answer: 2. Nylon 6, 6

Question 15. Which of the following is formed by condensation polymerisation?

1. Polythene
2. PVC
3. Teflon
4. Nylon 6, 6

Answer: 4. Nylon 6, 6

Question 16. Using which of the following can PVC be prepared?

1. CH₃CH=CH₂
2. C₆H5CH=CH₂
3. CH₂=CH-CI
4. CH₂ = CH

Answer: 3. CH₂=CH-CI

Question 17. Which of the following is a thermosetting polymer?

1. Nylon 6
2. Nylon 6, 6
3. Bakelite
4. SBR

Answer: 3. Bakelite

Question 18. In an elastomer, the intermolecular forces are

1. Nil
2. Weak
3. Strong
4. Very Strong

Answer: 2. Weak

Question 19. Which of the following is a biodegradable polymer?

1. Polythene
2. PVC
3. Bakelite
4. PHBV

Answer: 4. PHBV

Question 20. Which of the following is formed by condensation polymerisation?

1. Rayon
2. Nylon
3. Dacron
4. Artificial Silk

Answer: 1. Rayon and 4. Artificial Silk

Question 21. Which of the following is formed by condensation polymerisation?

1. Polyethylene
2. Bakelite
3. Melamine
4. Vulcanised Rubber

Answer: 2. Bakelite 3. Melamine and 4. Vulcanised Rubber

Question 22. Which of the following pairs of monomer molecules will form an addition polymer?

Answer: 1

Question 23. Which of the following pairs of monomer molecules will form a condensation polymer?

Answer: 3

Chemistry In Every Day Life

Chemistry influences every aspect of life. Food, clothing, furniture, medicines, and so on, are all associated with chemistry. Sugar and rubber (from plants); oils, fats, and proteins (from animals); insecticides, dyes, perfumes, explosives, lubricants, solvents, refrigerants, and fuels (petroleum) are products of organic compounds.

In this chapter, we shall discuss some important aspects of the chemistry of drugs, food, and cleansing agents.

Drugs

• A drug is a chemical that has a low molecular mass (~100 to 500 u). It interacts with a macromolecular target(s) and brings about a biological response. If this biological response helps prevent, manage or cure a disease, the chemical is called a medicine. Medicines are also used to alleviate pain.
• However, medicines should not be taken in dosages higher than required. Doing so would cause adverse effects. Remember that contraceptives and nutrients are not considered to be medicines/drugs.
• WHO (1966) has given a more comprehensive definition.
• “A drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient.”
• Ehrlich defined the term chemotherapy as treatment with chemicals that are toxic to infectious microorganisms but harmless to humans.

Classification Of Drugs

Drugs are classified in four different ways.

1. One classification is based on the pharmacological effect of the drugs available for the treatment of a particular type of symptom/disease. For example, analgesics are painkillers, antipyretics reduce fever, and antiseptics destroy or arrest the growth of microorganisms (bacteria).
2. Some drugs have a similar action on any biochemical process. For example, antihistamines inhibit the action of histamines, which cause allergic reactions.
3. Yet another classification is based on chemical structure. Drugs with common structural features do have similar pharmacological activity. For example, sulphonamides have the following common structural feature.

Drugs may also be classified on the basis of molecular targets. They usually interact with macromolecules such as carbohydrates, lipids, proteins, and nucleic acids. These macromolecules are called target molecules or drug targets. Drugs with common structural features may have the same mechanism of action on targets.

Catalytic Activity Of Enzymes

Almost all biological reactions in our body are carried out under the catalytic influence of enzymes. Hence, enzymes are a very important target of drug action. Drugs can either increase or decrease the rate of enzymatically mediated reactions.

Enzymes perform two major functions in their catalytic activity.

1. The catalytic activity of an enzyme is due to the presence of a specific site, on its surface, called the active site.

• This site is characterized by the presence of functional groups which form weak bonds, such as ionic bonds, hydrogen bonds or van der Waals bonds, with the substrate molecule.
• The enzyme can also be attached to the substrate through dipole-dipole attraction.
• An enzyme has a distinct cavity in which the substrate is bound. The cavity contains an active centre in which the amino acids are grouped in such a way as to enable them to combine with the substrate (Figure 16.1). The substrate induces a conformational change in the enzyme.
• This aligns amino acid residues or the other groups on the enzyme in the correct spatial orientation for substrate binding.

2. After attaining the abovementioned appropriate steric orientation, the reactants (enzyme and substrate) react to form the products. As the enzyme surface has no affinity for the product molecules, the latter leaves the enzyme surface quickly to make room for fresh molecules of substrates to be bound at the active site.

Inhibition Of Enzymes

Inhibition of enzymes is a common mode of drug action. Drugs can block the binding site of an enzyme and thus prevent the binding of the substrate. Such drugs are called enzyme inhibitors.

Drugs inhibit the attachment of the substrate to the active site in two different ways.

1. Some drugs compete with the normal substrate for attachment to the active site of the enzyme. Such drugs are called competitive inhibitors.

2. Some drugs react with an adjacent site (called an allosteric site) and not with the active site of the enzyme. They alter the enzyme in such a way that it loses its catalytic property—the attachment of inhibitors at the allosteric site changes the shape of the active site in such a way that the substrate is unable to recognize the active site.

The enzyme is made ineffective permanently if the bond formed between the inhibitor and the enzyme is a strong covalent bond. In such a case, the enzyme-inhibitor complex is degraded by the body, and a new enzyme is synthesised.

Receptors As Drug Targets

Many drugs exert their physiological effects by binding to a specific cellular binding site called a receptor. A drug (agonist) interacts with its receptor by the same kinds of bonding interactions-hydrogen bonding, electrostatic attractions, and van der Waals interactions.

The most important factor in bringing together a drug and a receptor is a close fit: the greater the affinity of a drug for its binding site, the higher is the drug’s potential biological activity.

Agonists: These are drugs that mimic a natural messenger and activate a receptor to produce an effect. These come into play when the natural messenger is not available.

Antagonists: Antagonists attach themselves to receptors and prevent them from functioning. They are useful when a message is required to be blocked.

Transfer Of Message Into The Cell By The Receptor

Our body has a large number of different receptors which interact with different chemical messengers. (Chemical messengers are in fact chemicals.) These receptors bind with specific chemical messengers because their binding sites (active sites) have different shapes, structures and amino acid compositions.

To accommodate a chemical messenger, the shape of the receptor site changes. This causes the transfer of a message into the cell. The chemical messenger gives a message to the cell without in fact entering the cell.

Types Of Drugs

Antacids

Under normal conditions, the stomach contains a certain amount of hydrochloric acid. The H+ ion of HCl participates in the process of digestion. An excess of this acid causes indigestion.

Excess HCl can be produced due to various reasons-overeating, the ingestion of certain kinds of spicy food, and increased stress.

The function of an antacid is to relieve indigestion by reducing the amount of stomach acid (gastric acid) to a normal level by neutralisation. Various compounds such as magnesium hydroxide, aluminium hydroxide and sodium bicarbonate, which have basic properties, can reduce acidity.

⇒ \(\mathrm{NaHCO}_3+\mathrm{H}^{+} \rightarrow \mathrm{H}_2 \mathrm{O}+\mathrm{CO}_2+\mathrm{Na}^{+}\)

⇒ \(\mathrm{Mg}(\mathrm{OH})_2+2 \mathrm{H}^{+} \rightarrow 2 \mathrm{H}_2 \mathrm{O}+\mathrm{Mg}^{2+}\)

⇒ \(\mathrm{Al}(\mathrm{OH})_3+3 \mathrm{H}^{+} \rightarrow 3 \mathrm{H}_2 \mathrm{O}+\mathrm{Al}^{3+}\)

However, excessive use of bicarbonate can cause hypersecretion of hydrochloric acid by the cells of the stomach lining, causing ulcers. Such ulcers can be life-threatening in advanced stages and the only treatment is to remove the ulcerated part of the stomach by surgery.

Metal hydroxides such as magnesium hydroxide and aluminum hydroxide are better options because they are insoluble and do not increase the pH value above 7. Although antacids do relieve acidity, they do not cure the cause of hyperacidity. Unless the cause of the hyperacidity is removed, antacids bring only temporary relief.

Histamine, a chemical, also stimulates the secretion of pepsin and hydrochloric acid in the stomach. A major breakthrough in the treatment of hyperacidity came when cimetidine, an antihistamine, was discovered to prevent the interaction of histamine with the receptors present in the stomach wall.

When cimetidine is administered, less acid is released in the stomach. Later, another drug, ranitidine (Zantac) was discovered and widely used in the treatment of hyperacidity.

Antihistamines

• Histamine has various functions. It causes dilation of blood capillaries. In addition, it makes the capillaries more permeable to blood fluids.
• Thus these fluids can readily leak out of the capillaries and cause swelling of the tissues. The compound causes contraction and spasms of the smooth muscles in the bronchial tubes.
• It can produce skin swellings and stimulate the glands that secrete watery nasal fluids, mucus, tears, saliva, and so on.
• Histamine is released in the body due to an allergic reaction caused by dust, pollen or certain kinds of food.
• The net effect of its actions includes runny nose, congestion, and sneezing. Antihistamine compounds work against the action of histamine.

Antihistamines and histamines have certain structural features in common, as shown below.

Due to the similarity in their structural features, antihistamines mimic histamines in their chemical reactions and can take the place of histamines. This, in effect, blocks the action of histamines and the symptoms caused by histamines begin to disappear.

Some commonly used antihistamines are Diphenylhydramine (Benadryl), Brompheniramine (Dimetapp), Promethazine (Phenergan), and Terfenadine (Trexyl, Seldane).

Antihistaminic agents are used primarily in the management of certain allergic disorders.

Many antihistamines such as diphenylhydramine and brompheniramine produce variable degree of central nervous system depression and as such they all have sedative action. Terfenadine is a nonsedative antiallergic.

Some antihistaminic drugs and their brand names:

Excess histamine production by the body also causes the hypersecretion of hydrochloric acid by the cells of the stomach lining, leading to the development of ulcers.

The antihistamines that block the histamine receptors, thereby preventing the allergic responses associated with excess histamine production, have no effect on HC1 production.

The reason is that a second kind of histamine receptor triggers the release of acid into the stomach.