Amines — Study Notes

1. Introduction

Amines are organic derivatives of ammonia in which one or more hydrogen atoms of NH3 are replaced by alkyl or aryl groups. They are characterised by the presence of a basic nitrogen atom bearing a lone pair of electrons, which gives them their distinctive basic character. Amines are found throughout nature in amino acids, alkaloids, and neurotransmitters, and they are industrially important as intermediates in the manufacture of dyes, drugs, and polymers.

Amines are classified as primary, secondary, or tertiary depending on the number of organic groups attached to the nitrogen atom. The chemistry of amines is dominated by the lone pair on nitrogen, which is responsible for their basicity, their nucleophilicity, and their ability to form hydrogen bonds. The basicity of amines depends on the electronic effects of the attached groups and the solvation of the ammonium ion formed on protonation.

The chapter covers the nomenclature and classification of amines, their methods of preparation including ammonolysis, reduction of nitro compounds and nitriles, and the Gabriel phthalimide synthesis. The physical properties and the reactions of amines, including acylation, diazotisation, and the reactions of diazonium salts, are studied. Distinguishing primary, secondary, and tertiary amines through the Hinsberg test and the carbylamine reaction is an important practical skill.

2. Classification and Nomenclature

Classification

• Primary (1°) amines: One alkyl or aryl group attached to nitrogen, e.g., CH3NH2.
• Secondary (2°) amines: Two organic groups attached, e.g., (CH3)2NH.
• Tertiary (3°) amines: Three organic groups attached, e.g., (CH3)3N.

Amines are further classified as aliphatic or aromatic depending on whether the nitrogen is attached to an aliphatic or aromatic group.

Nomenclature

In the IUPAC system, primary amines are named by replacing the -e of the parent alkane with -amine: CH3NH2 is methanamine, and CH3CH2CH2NH2 is propan-1-amine. In common nomenclature, they are named as alkylamines: CH3NH2 is methylamine and C2H5NH2 is ethylamine. Secondary and tertiary amines use the prefix N for substituents on nitrogen, for example, N-methylethanamine.

3. Methods of Preparation

Ammonolysis of Alkyl Halides

Alkyl halides react with ammonia to give primary, secondary, and tertiary amines, along with quaternary ammonium salts. The reaction gives a mixture, so an excess of ammonia is used to favour the primary amine: $$CH_3Br + NH_3 \rightarrow CH_3NH_2 + HBr$$

Reduction of Nitro Compounds

Nitroalkanes and nitroarenes are reduced to amines using H2/Pd, Fe/HCl, or LiAlH4: $$C_6H_5NO_2 \xrightarrow{[H]} C_6H_5NH_2$$

Reduction of Nitriles

Nitriles are reduced by LiAlH4 or H2/Ni to primary amines: $$RCN \xrightarrow{[H]} RCH_2NH_2$$

Reduction of Amides

Amides are reduced by LiAlH4 to primary amines.

Gabriel Phthalimide Synthesis

This is a convenient method for preparing pure primary aliphatic amines. Potassium phthalimide reacts with an alkyl halide to form N-alkylphthalimide, which on hydrolysis with dilute acid or alkali gives the primary amine and phthalic acid. This method avoids the formation of secondary and tertiary amines.

Hoffmann Bromamide Degradation

Acetamide reacts with bromine and sodium hydroxide to give methylamine: $$CH_3CONH_2 + Br_2 + 4NaOH \rightarrow CH_3NH_2 + 2NaBr + Na_2CO_3 + 2H_2O$$

4. Physical Properties

• Lower aliphatic amines are gases with a fishy smell; higher amines are liquids or solids.
• Amines are polar compounds that can form hydrogen bonds, so their boiling points are higher than the corresponding alkanes but lower than alcohols.
• The order of boiling points among isomeric amines is 1° > 2° > 3° because primary amines form the strongest hydrogen bonds.
• Lower amines are soluble in water because of hydrogen bonding; solubility decreases with increasing size of the alkyl group.

5. Basicity of Amines

Amines are basic because the nitrogen lone pair can accept a proton: $$R-NH_2 + H_2O \rightleftharpoons R-NH_3^+ + OH^-$$

The basicity depends on the availability of the lone pair. In the gas phase, basicity increases with increasing alkyl substitution: 3° > 2° > 1° > NH3, because alkyl groups donate electrons. In aqueous solution, solvation of the ammonium ion is important, and the order becomes 2° > 1° > 3° > NH3 because tertiary ammonium ions are less solvated and sterically hindered.

Aromatic amines such as aniline are much weaker bases than aliphatic amines because the lone pair on nitrogen is delocalised into the benzene ring by resonance. Electron-withdrawing groups on the ring further decrease basicity, while electron-donating groups increase it.

6. Chemical Reactions of Amines

Reactions with Acids

Amines react with acids to form ammonium salts: $$R-NH_2 + HCl \rightarrow R-NH_3^+Cl^-$$

Acylation

Primary and secondary amines react with acid chlorides or anhydrides to form amides. Tertiary amines do not undergo acylation because they have no hydrogen on nitrogen.

Carbylamine Reaction (Isocyanide Test)

Primary amines react with chloroform and alcoholic potassium hydroxide to give foul-smelling isocyanides: $$R-NH_2 + CHCl_3 + 3KOH \rightarrow R-NC + 3KCl + 3H_2O$$ This reaction is used to distinguish primary amines from secondary and tertiary amines.

Hinsberg Test

The Hinsberg reagent (benzenesulphonyl chloride) reacts differently with primary, secondary, and tertiary amines: - Primary amines give a soluble sulphonamide in alkali. - Secondary amines give an insoluble sulphonamide. - Tertiary amines do not react.

Reaction with Nitrous Acid

Primary aliphatic amines react with nitrous acid to give alcohols with evolution of nitrogen gas. Primary aromatic amines react to form diazonium salts: $$C_6H_5NH_2 + NaNO_2 + HCl \xrightarrow{273-278\ K} C_6H_5N_2^+Cl^- + NaCl + 2H_2O$$ Secondary amines give N-nitrosamines, and tertiary amines give water-soluble products.

Electrophilic Substitution in Aniline

Aniline is an ortho and para directing, highly activating group for electrophilic aromatic substitution. It reacts with bromine water to give tribromoaniline, but direct bromination with bromine in a suitable solvent can give the monobrominated product.

7. Diazonium Salts

Diazonium salts have the general formula ArN2+X- and are prepared from aromatic primary amines at low temperature. They are highly versatile synthetic intermediates.

Reactions of Diazonium Salts

• Replacement by Cl, Br, I: Sandmeyer reaction using cuprous halides; Gattermann reaction using copper powder and the halogen acid.
• Replacement by -OH: Boiling diazonium salt with water gives phenol.
• Replacement by -CN: Gives aryl cyanides, which can be hydrolysed to acids.
• Coupling reactions: Diazonium salts couple with phenols and anilines to form highly coloured azo compounds, used as dyes.

Quick Revision Tables

Table 1: Methods of Preparation

Table 2: Distinguishing Tests

Mind Map

Important Diagrams (SVG)

Diagram 1: Basicity Comparison of Amines

Diagram 2: Preparation and Reactions of Diazonium Salts

Common Mistakes

1. Believing tertiary amines are the strongest bases in water; the aqueous order is 2° > 1° > 3° > NH3 because of solvation effects.
2. Stating that aniline is a strong base; it is much weaker than aliphatic amines because the nitrogen lone pair is delocalised into the ring.
3. Applying the carbylamine reaction to secondary and tertiary amines; it is specific to primary amines.
4. Forgetting that the Gabriel phthalimide synthesis gives only primary amines and cannot be used for aromatic primary amines.
5. Confusing the products of the Hinsberg test: primary amines give soluble sulphonamides, secondary give insoluble ones, and tertiary do not react.
6. Running the diazotisation at room temperature; it must be carried out at 273-278 K because diazonium salts decompose on warming.
7. Believing that ammonolysis gives a pure product; it always gives a mixture of primary, secondary, and tertiary amines.

Exam Tips

1. Memorise the aqueous basicity order 2° > 1° > 3° > NH3 and justify it with hydration and inductive effects.
2. Learn the carbylamine reaction and the Hinsberg test as the standard way to distinguish the three classes of amines.
3. Remember the Gabriel phthalimide synthesis produces pure primary amines without contamination.
4. Know that diazonium salts must be kept at 273-278 K and that the Sandmeyer reaction uses cuprous halides.
5. For aniline, remember its electrophilic substitution gives ortho and para products, and bromine water gives tribromoaniline.
6. Practise naming amines both by IUPAC (propan-1-amine) and common (propylamine) systems, and use N- for substituents on nitrogen.

Conclusion

Amines are fundamental nitrogen-containing compounds whose chemistry is defined by the lone pair on nitrogen. Their basicity, which depends on alkyl substitution, solvation, and resonance in aromatic systems, governs their reactivity and their behaviour in biological systems. The multiple methods of preparation, from ammonolysis to the Gabriel phthalimide synthesis, provide controlled routes to primary, secondary, and tertiary amines. Distinguishing tests such as the carbylamine reaction and the Hinsberg test allow chemists to identify amine classes, while diazonium salts open a vast array of synthetic transformations from haloarenes to azo dyes. Understanding amines completes the picture of functional group chemistry needed for amino acids, peptides, and many pharmaceuticals, and forms a foundation for the study of biomolecules in the next chapter.

Test Your Understanding

1. Classify CH3NH2, (CH3)2NH, and (CH3)3N as primary, secondary, or tertiary amines.
2. Explain why aniline is a weaker base than cyclohexylamine.
3. Write the reaction for the Gabriel phthalimide synthesis of propylamine.
4. How would you distinguish a primary amine from a secondary amine using the Hinsberg test?
5. Give two important reactions of benzenediazonium chloride.