26. Amines

Show how you would accomplish the following synthetic conversions.

(c) pentanoic acid → pentan-1-amine

Reductive amination of aldehydes and ketones is a versatile method for attaching alkyl groups to amines, but the alkyl group is restricted to a 1° or 2° carbon by this method. Prof. Phil Baran of Scripps Research Institute has reported (Science, 2015, 348 (6237), 886–891) a novel way to reduce an aromatic nitro group and add the resulting amine to an alkene so that the aromatic amine is bonded to a 3° carbon—all in a continuous sequence of reactions.

For example:

Predict the products using these starting materials, all of which are reported in this paper.

(c)

(d)

Predict the products of the following reactions:

(k)

Propose a mechanism for the coupling of acetic acid and aniline using DCC as a coupling agent.

At the end of a reduction, there was found to be a small amount of unreacted amide along with the amine product dissolved in diethyl ether. How might you remove the amine from the ether?

How can the following compounds be prepared from the given starting materials?

d.

Predict the products of the following reactions:

(d)

Show how m-toluidine can be converted to the following compounds, using any necessary reagents.

(b)

Give the expected products of lithium aluminum hydride reduction of the following compounds (followed by hydrolysis).

(a) butyronitrile

(b) N-cyclohexylacetamide

(c) ε-caprolactam

Several additional amine syntheses are effectively limited to making primary amines. The reduction of azides and nitro compounds and the Gabriel synthesis leave the carbon chain unchanged. Formation and reduction of a nitrile adds one carbon atom. Show how these amine syntheses can be used for the following conversions.

(c) 1-bromo-3-phenylheptane → 3-phenylheptan-1-amine

How could you convert N-methylbenzamide to the following compounds?

a. N-methylbenzylamine

Synthesize from benzene. (Hint: All of these require diazonium ions.)

(d) 4-methoxyaniline

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses.

(a) benzoic acid → benzylamine