Amines constitute an important class of organic compounds derived by replacing one or more hydrogen atoms of ammonia ($NH_3$) molecule by alkyl/aryl group(s).
In nature, they occur among proteins, vitamins, alkaloids, and hormones. Biologically active examples include:
Like ammonia, the nitrogen atom of amines is trivalent and carries an unshared pair of electrons. Nitrogen orbitals in amines are $sp^3$ hybridised, and the geometry of amines is pyramidal.
Each of the three $sp^3$ hybridised orbitals of nitrogen overlaps with orbitals of hydrogen or carbon. The fourth orbital contains an unshared pair of electrons. Due to the presence of this unshared pair, the angle $C-N-E$ (where $E$ is $C$ or $H$) is less than $109.5^\circ$ (e.g., $108^\circ$ in trimethylamine).
Amines are classified as primary ($1^\circ$), secondary ($2^\circ$), and tertiary ($3^\circ$) depending upon the number of hydrogen atoms replaced by alkyl or aryl groups in the ammonia molecule:
Amines are called 'simple' when all alkyl or aryl groups are the same, and 'mixed' when they are different.
In the common system, aliphatic amines are named by prefixing the alkyl group to amine (e.g., methylamine). In the IUPAC system, they are named as alkanamines (replacing the 'e' of alkane with 'amine').
For secondary and tertiary amines, the locant $N$ is used to designate substituents attached to the nitrogen atom (e.g., $CH_3NHCH_2CH_3$ is named as N-methylethanamine).
Arylamines are named as derivatives of aniline (or benzenamine).
Nitro compounds are reduced to amines by passing hydrogen gas in the presence of finely divided nickel, palladium, or platinum, or by reduction with metals in acidic medium.
$$R-NO_2 + 3H_2 \xrightarrow{Pd/Ethanol} R-NH_2 + 2H_2O$$
$$Ar-NO_2 \xrightarrow{Fe + HCl \text{ or } Sn + HCl} Ar-NH_2$$
Note: Reduction with iron scrap and hydrochloric acid is preferred because $FeCl_2$ formed gets hydrolysed to release hydrochloric acid, requiring only a small amount of $HCl$ to initiate the reaction.
The carbon-halogen bond in alkyl or benzyl halides can be cleaved by a nucleophile like ammonia. This process is called ammonolysis.
$$NH_3 + R-X \rightarrow R-\overset{+}{N}H_3 \bar{X} \xrightarrow{NaOH} R-NH_2 + H_2O + NaX$$
The primary amine can further react with alkyl halide to form secondary and tertiary amines, and finally quaternary ammonium salts:
$$R-NH_2 \xrightarrow{RX} R_2NH \xrightarrow{RX} R_3N \xrightarrow{RX} R_4\overset{+}{N}\bar{X}$$
Order of reactivity of halides: $RI > RBr > RCl$.
Nitriles on reduction with lithium aluminium hydride ($LiAlH_4$) or catalytic hydrogenation produce primary amines. This reaction is used for the ascent of the amine series (adding one carbon atom).
$$R-C\equiv N \xrightarrow{H_2/Ni \text{ or } Na(Hg)/C_2H_5OH} R-CH_2-NH_2$$
Amides on reduction with lithium aluminium hydride yield amines.
$$R-CO-NH_2 \xrightarrow{(i) LiAlH_4, (ii) H_2O} R-CH_2-NH_2$$
Used for the preparation of primary aliphatic amines. Phthalimide on treatment with ethanolic $KOH$ forms potassium phthalimide, which on heating with an alkyl halide followed by alkaline hydrolysis produces a primary amine.
Note: Aromatic primary amines cannot be prepared by this method because aryl halides do not undergo nucleophilic substitution with the phthalimide anion.
An amide is treated with bromine in an aqueous or ethanolic solution of sodium hydroxide, yielding a primary amine containing one carbon atom less than the starting amide.
$$R-CO-NH_2 + Br_2 + 4NaOH \rightarrow R-NH_2 + Na_2CO_3 + 2NaBr + 2H_2O$$
Amines are basic in nature and react with acids to form salts:
$$R-NH_2 + HX \rightleftharpoons R-\overset{+}{N}H_3 \bar{X}$$
The basic strength is expressed in terms of $K_b$ or $pK_b$ ($pK_b = -\log K_b$). A smaller $pK_b$ value indicates a stronger base.
Alkylation: Amines react with alkyl halides to undergo alkylation.
Acylation: Aliphatic and aromatic primary and secondary amines react with acid chlorides, anhydrides, and esters by nucleophilic substitution to form amides. The reaction is carried out in the presence of a base stronger than the amine (like pyridine) to remove $HCl$.
$$R-NH_2 + CH_3COCl \xrightarrow{\text{Pyridine}} R-NH-CO-CH_3 + HCl$$
Aliphatic and aromatic primary amines on heating with chloroform and ethanolic potassium hydroxide form foul-smelling isocyanides (carbylamines). This is used as a test for primary amines.
$$R-NH_2 + CHCl_3 + 3KOH \xrightarrow{\Delta} R-NC + 3KCl + 3H_2O$$
Benzenesulphonyl chloride ($C_6H_5SO_2Cl$) is used to distinguish primary, secondary, and tertiary amines:
Diazonium salts have the general formula $R-\overset{+}{N}_2 \bar{X}$ where $R$ is an aryl group and $X^-$ can be $Cl^-$, $Br^-$, $HSO_4^-$, $BF_4^-$, etc.
Prepared by the reaction of aniline with nitrous acid at $273\text{--}278\text{ K}$. This process is called diazotisation.
$$C_6H_5NH_2 + NaNO_2 + 2HCl \xrightarrow{273\text{--}278\text{ K}} C_6H_5\overset{+}{N}_2\bar{C}l + NaCl + 2H_2O$$
Benzenediazonium chloride is a colourless crystalline solid, readily soluble in water, stable in the cold but reacts with water when warmed.
Reactions are divided into two categories:
$$Ar\overset{+}{N}_2\bar{X} \xrightarrow{Cu_2Cl_2/HCl} ArCl + N_2$$
$$Ar\overset{+}{N}_2\bar{X} \xrightarrow{Cu_2Br_2/HBr} ArBr + N_2$$
$$Ar\overset{+}{N}_2\bar{X} \xrightarrow{CuCN/KCN} ArCN + N_2$$
Diazonium salts react with phenol or aniline to form brightly coloured azo compounds (dyes):
Diazonium salts are excellent intermediates for introducing groups like $-F$, $-Cl$, $-Br$, $-I$, $-CN$, $-OH$, and $-NO_2$ into the aromatic ring at positions that cannot be easily substituted directly.