Reaction of an Introverted Carboxylic Acid with Carbodiimide

Abstract

The reaction of carboxylic acids with carbodiimides is reviewed, and an "introverted" carboxylic acid is proposed as a means of trapping reactive intermediates along the reaction pathway. The introverted acid is a cavitand with the carboxylic function directed toward the floor of the cavity. Its reaction with diisopropyl carboodiimide gives a covalent adduct that is either the elusive O-acylisourea or the commonly encountered N-acylurea.

Figure 1

The introverted acid 1.

Figure 2

Upfield region of ¹H NMR spectrum (600 MHz, 300 K, benzene-d₆) in the reaction of 1 with diisopropylcarbodiimide.

Figure 3

a) External nucleophiles and the O-acylisourea 2 and b) intramolecular rearrangement to a tetrahedral intermediate.

Figure 4

Possible rearrangement to the N-acylurea via an acylium ion.

Scheme 1

Typical reactions of carboxylic acids and amines with dicyclohexylcarbodiimide.

Scheme 2

N-acylureas from the reaction of symmetrical anhydrides of BOC-protected amino acids with carbodiimides

Scheme 3

Trapping the reactive intermediate in the reaction of 1 with diisopropylcarbodiimide

Scheme 4

An improved procedure for synthesis of the introverted acid 1