Q38E - Organic Chemistry (Mcmurry)

Question

21-38 Treatment of an a-amino acid with DCC yields a 2,5-diketopiperazine.Propose a mechanism.

Step-by-Step Solution

Answer

When an $\stackrel{°}{\mathrm{I}}\pm -$  amino acid is treated with DCC, two steps are required to produce 2,5-diketopiperazine.

1. A dipeptide is formed, and 
2. The dipeptide is converted to 2,5-diketopiperazine.

The following is the mechanism for the production of a dipeptide.

Below is the mechanism for converting the dipeptide to 2,5-diketopiperazine.

Step 1: Introduction to the Concept

A nucleophilic substitution reaction occurs when an electron-rich nucleophile contacts a positively charged electrophile in order to replace a leaving group.

Step 2: Solution Explanation

i)  Formation of the dipeptide: 

An intermediate is produced by the nucleophilic attack of the carboxylate group on the carbon in DCC's $\mathrm{C}=\mathrm{N}$  followed by a proton abstraction. Another intermediate is produced by a nucleophilic attack by the amino group of the second amino acid and the consequent loss of a proton. The dipeptide is produced after the intermediate removes dicyclohexylurea.

ii)  Conversion of the dipeptide to 2,5-diketopiperazine:

The intermediate is produced by the nucleophilic assault of the carboxylate end of the dipeptide on the carbon in DCC's $\mathrm{C}=\mathrm{N}$ followed by a proton abstraction. Another intermediate is produced by another intermolecular nucleophilic attack by the amino terminus of the dipeptide on a carbonyl carbon and subsequent proton loss. 

Dicyclohexylurea is subsequently removed from the intermediate, yielding 2,5-diketopiperazine.

Below is the mechanism for converting the dipeptide to 2,5-diketopiperazine.