Question

Write chemical equations of three methods of preparation of amine and also write the mechanism of ammonolysis of alkyl halides.

Hint:

Ammonolysis of \(\mathrm{R{-}X}\) is $S_N2$; use excess ammonia to limit over-alkylation and prefer primary halides for best yield.

Answer 1

Part–II: Three methods of preparation of amines + mechanism of ammonolysis
(A) Three preparations (with equations)
1) Reduction of nitro compounds:
\[ \mathrm{ArNO_2 \xrightarrow{Sn/HCl \; or \; H_2/Ni} ArNH_2 + H_2O} \]
2) Gabriel phthalimide synthesis (only 1$^\circ$ alkyl amines):
\[ \mathrm{Phth{-}NH \xrightarrow{KOH} Phth{-}N^-K^+ \xrightarrow{R{-}X} Phth{-}NR \xrightarrow{H_2N{-}NH_2} RNH_2 + \text{phthalylhydrazide}} \]
3) Hofmann bromamide degradation (1 carbon less):
\[ \mathrm{RCONH_2 \xrightarrow{Br_2/NaOH} RNH_2 + CO_2} \]
(B) Mechanism of ammonolysis of alkyl halides (formation of amines)
Overall reaction (primary example):
\[ \mathrm{R{-}X + NH_3 \xrightarrow{EtOH,\;sealed\ tube} RNH_2 + HX} \]
Step 1: $S_N2$ backside attack (rate = $k$[R–X][NH$_3$]).
\[ \mathrm{R{-}X + :NH_3 \rightarrow [R\cdots NH_3 \cdots X]^\ddagger \rightarrow R{-}NH_3^+ + X^-} \]
Step 2: Base deprotonation.
\[ \mathrm{R{-}NH_3^+ + NH_3 \rightarrow R{-}NH_2 + NH_4^+} \]
Side reactions (over-alkylation):
\[ \mathrm{R{-}NH_2 + R{-}X \rightarrow R_2NH \rightarrow R_3N \rightarrow [R_4N]^+X^-} \]
Hence, to maximize 1$^\circ$ amine, use \(\mathrm{NH_3}\) in excess and primary halides (less steric hindrance). Tertiary halides undergo elimination rather than $S_N2$.