Amines

1. Introduction

Alkyl or aryl derivatives of ammonia are regarded as amines. These are obtained by replacing one or more hydrogen atoms by alkyl or aryl groups. Amines are classified as primary, secondary or tertiary depending upon whether one, two or three atoms of hydrogen have been replaced by alkyl or aryl groups.

NH3−→+CH3– HCH3NH2Methylamine1°(Primary)−→+CH3– H(CH3)2NHDimethylamine2°(Secondary)−→+CH3– H(CH3)3NTrimethylamine   3°(Tertiary)

Thus, characteristic functional groups for 1°, 2° or 3° amines are:

—NH2      Primary—N|H    Secondary—N|— Tertiary

Amines are said to be ‘simple’ when all the alkyl or aryl groups are the same, and ‘mixed’ when they are different.

There is another class of compounds wherein all the four hydrogen atoms of an ammonium salt have been replaced by alkyl or aryl groups. Such compounds are named as quaternary ammonium salts.

[NH4]+X–→+4R–4H[NR4]+X–Tetraalkylammoniumhalide

2. Structure of Amines

Like ammonia, nitrogen atom of amines is trivalent and carries an unshared pair of electrons. Nitrogen orbitals in amines are therefore sp3 hybridised and the geometry of amines is pyramidal. Each of the three sp3 hybridised orbitals of nitrogen overlap with orbitals of hydrogen or carbon depending upon the composition of the amines. The fourth orbital of nitrogen in all amines contains an unshared pair of electrons. Due to the presence of unshared pair of electrons, the angle C—N—E, (where E is C or H) is less than 109.5°; for instance, it is 108° in case of trimethylamine as shown in Fig. 13.1 alongside.

3. Nomenclature

In the trivial system, amines are named as alkylamine but in the IUPAC system, these are named as alkanamine (replacing ‘e’ of alkane with amine).

Table 13.1: Nomenclature of Some Amines

Common Name	Structural Formula	IUPAC Name
Ethyl amine	CH3—CH2—NH2	Ethanamine
Isopropyl amine	CH3—CH—|CH3NH2	Propan-2-amine
Ethyl methyl amine	CH3—CH2—NH—CH3	N-Methylethanamine
N, N-Diethylbutylamine	C2H5—N—|C2H5CH2—CH2—CH2—CH3	N, N-Diethylbutan-1- amine
Allylamine	CH2—CH—CH2—NH2	Prop-2-en-1-amine
Hexamethylenediamine	H2N—(CH2)6—NH2	Hexane-1, 6-diamine
Aniline		Benzenamine or Aniline
o-Toluidine		2-Methylaniline
N, N-Dimethylaniline		N, N-Dimethylbenzenamine

4. Preparation of Amines: Amines are prepared by the following methods:

(a) Reduction of nitro compounds:

R—NO2+3H2→NiR—NH21° amine+2H2O

CH3—CH2—NO2Nitroethane+6[H]−→−−−−orSn/HCl (conc.)Fe/HCl (conc.)CH3—CH2—NH2+Ethanamine2H2O

(b) Ammonolysis of alkyl halides:

R—X +2NH3(excess)→R—NH21° amine(Major product)+NH4X

If alkyl halide is in excess, the amine formed further reacts with alkyl halide to form 2°, 3° amines and finally quaternary ammonium salts.

R—NH21° amine−→+R—XR2NH2° amine−→+R—XR3N3° amine−→+R—XR4N+X–Quaternaryammonium salt

(c) Reduction of nitriles:

R—C≡≡N+2H2→NiR—CH2—NH21° amine

R—C≡≡N+4[H]−→−−−or LiAlH4Na(Hg)/C2H5OHR—CH2—NH21° amine

(d) Reduction of amides:

R—CONH2Acid amide+4[H]−→−−LiAlH4/etherR—CH2—NH21°amine+H2O

(e) Hoffmann’s bromamide degradation reaction:

R—CONH2Acid amide+Br2+4NaOH→R—NH21° amine+Na2CO3+2NaBr+2H2O

(f) Gabriel phthalimide synthesis:

Aromatic amines cannot be prepared by this method because aryl halides do not undergo nucleophilic substitution with the anion formed by phthalimide.

Preparation of Aniline:

(i) From nitrobenzene

(ii) By Hoffmann bromamide degradation reaction

5. Physical Properties

(i) The lower members are combustible gases, members from C3 to C11 are volatile liquids and from C12 onwards are solids. Lower aromatic amines are liquids while the higher ones are low melting solids.

(ii) Pure amines are almost colourless but develop colour on keeping in air for long time, especially, the aromatic amines. The colouration is due to oxidation of amines by air.

(iii) The boiling point increases with the increase in molecular weight. However, primary and secondary amines have higher boiling points than the tertiary amines of the same molecular weight. This is again due to the possibility of intermolecular hydrogen bonding between molecules of primary as well as secondary amines.

The hydrogen bonding between amine molecules is weaker than that between alcohols or carboxylic acids therefore amines have lower boiling points than the alcohols or carboxylic acids of comparable molecular masses.

(iv) The lower members are readily soluble in water, the solubility in water decreases and in organic solvents (alcohol and ether) increases with the increase in molecular weight.

Solubility of all the three classes of aliphatic amines in water is due to the formation of hydrogen bond between amine and water molecules. However, in higher amines, the alkyl group predominates over the amino group with the result that they have less tendency for forming hydrogen bond with water. This explains why the higher amines are insoluble in water.

Aromatic amines are insoluble in water. This is because of the larger hydrocarbon part. Thus, aniline is almost insoluble in water. However, all amines are quite soluble in organic solvents like benzene, ether, alcohol, etc.

6. Basic Character of Amines: Amines have a lone pair of electrons on nitrogen atom due to which they behave as Lewis base. Basic character of amines can be better understood in terms of Kb and pKb values as explained below.

R—NH2+H2O⇌R—N+H3+O–H

Kb=[R—N+H3][O–H][R—NH2]

pKb = – log Kb

Larger the value of Kb or smaller the value of pKb stronger is the base.

(a) Amines versus alcohols, ethers and esters: Since nitrogen is less electronegative than oxygen, it is in a better position to accommodate the positive charge of the proton. Therefore, amines are more basic than alcohols, ethers, esters, etc.

(b) Alkylamines versus ammonia: In aliphatic amines, the electron-releasing alkyl groups stabilise their ammonium cations by dispersing the positive charge, and in parent amines make the nitrogen unshared electrons more available for sharing with a proton. Thus, the basic character of aliphatic amines should increase with the increase of alkyl substitution. But it does not occur in a regular manner as a secondary aliphatic amine is unexpectedly more basic than a tertiary amine in solutions.

Basicity Order: (Et)2NH > Et3N > EtNH2 > NH3; (Me)2NH > MeNH2 > (Me)3N > NH3

In gas phase, where the solvent effect is missing, the basic trend in nature is as expected, i.e., tertiary amine > secondary amine > primary amine > ammonia.

Anomalous basic strength of tert-alkylamines: In aqueous solution, the substituted ammonium cations are stabilised not only by electron-releasing effect of the alkyl groups but also by solvation with water molecules. It is a combination of electron-releasing, H-bonding and steric factors that determine the stability of the ammonium cations in solution and thereby resulting in the basic strength order of aliphatic amines as secondary > tertiary > primary amines.

(c) Aromatic amines versus ammonia and aliphatic amines: Aromatic amines are weaker bases than ammonia and aliphatic amines. Since resonance stabilises an aromatic amine more than it stabilises its ammonium cation, the proton acceptability and thereby basic strength of aromatic amines would be less. It may also be argued that due to resonance, unshared electrons on nitrogen in aromatic amines are less available for sharing with a proton—a feature opposite to that in alkyl amines.

(d) Effect of substituent on the basicity of aromatic amines:

(i) Electron-donating groups such as —CH3, —OCH3, –NH2, etc., increase the basicity while electron-withdrawing substituents such as —NO2, —CN, halogens, etc., decrease the basicity of amines. The effect of these substituents is more at p- than at m-positions.

(ii) Among the isomeric toluidines, the basic strength with respect to aniline decreases as:

(iii) The order of basic strength of some amino compounds:

Ortho-substituted anilines are weaker bases than aniline irrespective of the nature of the substituent. This is called ortho-effect and it is probably due to a combination of steric and electronic factors.

7. Chemical Properties of Amines:

(a) Alkylation:

(b) Acylation:

R—NH2+R′—C||O—Cl→BaseR—NH—C||O—R′N−substituted amide+HCl

(c) Reaction with chloroform (Carbylamine reaction):

R—NH2 +CHCl3+3KOH (alc.)→ΔR—NCAlkylcarbylamine   +3KCl+3H2O

(d) Reaction with nitrous acid:

Reaction with nitrous acid helps in distinguishing between amines. Primary amines react with nitrous acid to form alcohols.

R—NH21° amine+HONO−→−−NaNO2/HClR—OH+N2+H2O

Secondary amines react with nitrous acid to form a yellow green oily layer of N-nitrosoamines. N-Nitrosoamines on warming with a crystal of phenol and a few drops of conc. H2SO4 form green solution which when treated with aqueous NaOH, turns deep blue and then red on dilution. This reaction is called Liebermann’s nitroso reaction.

R2NH2° Amine+HNO2→R2N—N==ON−Nitrosoamine+H2O

tert-Amines readily dissolve in nitrous acid forming crystalline trialkyl ammonium nitrite.

R3N +HNO2→R3N+HNO–2Trialkyl ammonium nitrite

(e) Diazotization:

(f) Electrophilic substitution reactions:

Due to resonance, electron density increases at ortho and para positions as compared to meta positions. Therefore, —NH2 group directs the incoming group to ortho and para positions.

(i) Bromination:

(ii) Nitration:

In strongly acidic medium, significant amount of meta isomer is obtained. This is due to the formation of anilinium ion which is meta directing. However, the p-nitro derivative can be obtained as the major product by protecting the —NH2 group by acetylation reaction.

(iii) Sulphonation:

(iv) Friedel–Crafts reaction:

Due to salt formation, nitrogen of aniline acquires positive charge and thus acts as a strong deactivating group and hence does not allow Friedel–Crafts reaction to occur.

8. Diazonium Salts

(a) General formula: RN2+X–

where R stands for an aryl group and X– ion may be Cl–, Br–, HSO4–, BF4–, etc. The N+2(—N+≡N) is called the diazonium group.

(b) Stability of diazonium salts:

Arenediazonium salts are much more stable than alkyl diazonium salts. The stability of arene diazonium salt is due to the dispersal of the positive charge over the benzene ring as shown below.

(c) Preparation of diazonium salts

This process of conversion of a primary aromatic amine into its diazonium salt is called diazotization.

9. Chemical Properties of Diazonium Salts:

The reactions of diazonium salts can be divided into two categories, namely

(a) Reactions involving displacement of nitrogen.

(b) Reactions involving retention of diazo group.

(a) Reactions involving displacement of nitrogen:

(i) Replacement by halide or cyanide ion:

ArN2+X–−→−−−  Cu2Cl2/HCl  ArCl +  N2ArN2+X–−→−−− Cu2Br2/HBr  ArBr +  N2ArN2+X–−→−−CuCN/KCNArCN +  N2⎫⎭⎬⎪⎪⎪⎪⎪⎪⎪⎪Sandmeyer’s reactions

ArN2+X–−→−  Cu/HCl  ArCl+N2+CuXArN2+X–−→− Cu/HBr  ArBr+N2+CuX⎫⎭⎬Gatterman’s reaction

(ii) Replacement by iodide ion:

ArN2+Cl–Benzene diazoniumchloride+KI→ArIIodobenzene +KCl+N2

(iii) Replacement by fluoride ion:

ArN2+Cl–+HBF4→ArN2+BF–4→ΔAr—F+BF3+N2

(iv) Replacement by H:

ArN2+Cl–+H3PO2+H2O→ArH+N2+H3PO3+HClArN2+Cl–+CH3—CH2—OH→ArH+N2+CH3—CHO+HCl

(v) Replacement by hydroxyl group:

ArN2+Cl–+H2O→ΔArOHPhenol+N2+HCl

(vi) Replacement by —NO2 group:

(b) Reactions involving retention of diazo group:

Coupling reaction: The reaction of diazonium salts with phenols and aromatic amines to form azo compounds of the general formula, Ar—N—N—Ar is called coupling reaction. The mechanism is basically that of electrophilic substitution where the diazonium ion is electrophile. In this reaction, the nitrogen atoms of the diazo group are retained in the product. The coupling with phenols takes place in mildly alkaline medium while with amines, it occurs under faintly acidic conditions. For example,

Coupling generally occurs at the p-position, w.r.t., the hydroxyl or the amino group, if free, otherwise it takes place at the o-position.

10. Some Important Name Reactions

(a) Gabriel phthalimide synthesis: This reaction is used for the preparation of aliphatic primary amines. In this reaction, phthalimide is first of all treated with ethanolic KOH to form potassium phthalimide. Potassium phthalimide on treatment with alkyl halide gives N-alkyl phthalimide, which on hydrolysis with dilute hydrochloric acid gives a primary amine as the product.

(b) Hoffmann bromamide reaction: When a primary acid amide is heated with an aqueous or ethanolic solution of NaOH or KOH and bromine (i.e., NaOBr or KOBr), it gives a primary amine with one carbon atom less.

R—CONH2Acid amide+Br2+4NaOH→R—NH21° amine   +Na2CO3+2NaBr+2H2O

(c) Sandmeyer’s reaction: The Cl–, Br– and CN – nucleophiles can easily be introduced in the benzene in the presence of Cu (I) ion. This reaction is called Sandmeyer’s reaction.

(d) Gatterman’s reaction: Chlorine or bromine can be introduced in benzene ring by treating the diazonium salt solution with corresponding halogen acid in the presence of copper powder.

(e) Carbylamine reaction (Isocyanide test): Aliphatic and aromatic primary amines when heated with chloroform and alcoholic solution of KOH give isocyanides (carbylamines) which have extremely unpleasant smell.

R—NH21° amine+CHCl3+3KOH (alc.)→ΔR—NCAlkylisocyanide+3KCl+3H2O

11. Uses of Amines:

(i) The quaternary ammonium salts of long chain aliphatic amines are used as detergents, e.g., cetyltrimethyl ammonium chloride.

(ii) Low molecular mass aliphatic amines are used as reagents in organic synthesis and as intermediates in the manufacture of drugs.

(iii) Aniline is used in the manufacture of dyes, dye intermediates and sulpha drugs.

12. Test for Amines

(a) Hinsberg’s test: In this test, the amine is first treated with Hinsberg’s reagent (benzenesulphonyl chloride) and then shaken with aqueous KOH solution when the three amines behave in different ways.

(i) A 1° amine gives a clear solution which on acidification gives an insoluble N-alkyl benzene sulphonamide.

(ii) A 2° amine gives an insoluble N, N-dialkyl benzene sulphonamide which remains unaffected on addition of acid.

(iii) A 3° amine does not react at all.

C6H5SO2ClBenzenesulphonylchloride+R3N3°amine→KOHNoreaction

(b) Isocyanide test (Carbylamine test): Primary amines (aliphatic as well as aromatic) react with chloroform in the presence of alcoholic KOH to form foul smelling carbylamine.

R—NH21° amine+CHCl3+3KOH (alc.)→ΔR—NCAlkylisocyanide+3KCl+3H2O

Secondary and tertiary amines (aliphatic as well as aromatic) do not give this test.

(c) Azo dye test: It involves the reaction of any aromatic primary amine with HNO2 (NaNO2 + dil. HCl) at 273–278 K followed by treatment with an alkaline solution of 2-naphthol, where a brilliant yellow, orange or red coloured dye is obtained.

Aliphatic primary amines under these conditions give a brisk evolution of N2 gas with the formation of primary alcohols, i.e., the solution remains clear.

RNH2+HONO−→−273−278KR—OH    Alcohol+N2↑⏐⏐+H2OC2H5NH2Ethylamine+HONO−→−273−278KC2H5OHEthylalcohol+N2↑⏐⏐⏐+H2O

RNH2+HONO−→−273−278KR—OH    Alcohol+N2↑⏐⏐+H2OC2H5NH2Ethylamine+HONO−→−273−278KC2H5OHEthylalcohol+N2↑⏐⏐⏐+H2O