Question

Show how to synthesize the following amines from the indicated starting materials by reductive amination.

(a) benzylmethylamine from benzaldehyde

(b) N-benzylpiperidine from piperdine

(c) N-cyclohexylaniline from cyclohexanone

(d) cyclohexylamine from cyclohexanone

(e)

(f)

Short answer

(a)

(b)

(c)

(d)

(e)

(f)

Step-by-step solution

Reductive amination

The most useful method for synthesis of amines is the reductive amination. In this process, 1⁰ or 2⁰ alkyl group is added to the nitrogen atom. Generally, aldehyde is used to add 1⁰ alkyl group and ketone is used to add 2⁰ alkyl group.

Synthetic methodology

a.

Benzalhedyde combines with methylamine (a primary amine) to undergo a condensation process to form (E)-N-benzylidenemethanamine (a Schiff base) which on further reduction with LiAlH₄ (lithium aluminum hydride) gives N-methyl-1-phenylmethanamine ( a secondary amine).

reaction a

b.

Benzalhedyde combines with piperidine (a secondary amine) to undergo a condensation process to form an iminium salt (1-benzylidenepiperidin-1-ium) which on further reduction with NaBH(OAc)₃ (sodium triacetoxy borohydride)gives 1-benzylpiperidine ( a tertiary amine).

reaction b

c.

Cylohexanone combines with aniline (a primary amine) to undergo a condensation process to form N-cyclohexylideneaniline (a Schiff base) which on further reduction with LiAlH₄ (lithium aluminum hydride) gives N-cyclohexylaniline ( a secondary amine).

reaction c

d.

Cylohexanone combines with hydroxylamine (zero alkyl groups) to undergo a condensation process to form cyclohexanone oxime which on further reduction with LiAlH₄ (lithium aluminum hydride) gives cyclohexanamine ( a primary amine).

reaction d

e.

1-phenylpropan-2one combines with hydroxylamine (zero alkyl groups) to undergo a condensation process to form (Z)-1-phenylpropan-2-one oxime which on further reduction with LiAlH₄ (lithium aluminum hydride) gives ±amphetamine or 1-phenylpropan-2-amine ( a primary amine).

reaction e

f.

Cyclopenatnone combines with piperidine (a secondary amine) to undergo a condensation process to form an iminium salt (1-cyclopentylidenepiperidin-1-ium) which on further reduction with NaBH(OAc)₃ (sodium triacetoxy borohydride)gives 1-cyclopentylpiperidine ( a tertiary amine).

reaction f