IV-Acylureas

NL Benoiton, FMF Chen. Reaction of A-t-butoxycarbonylamino acid anhydrides with tertiary amines and carbodiimides. New precursors for 2-f-butoxyoxazol-5(4//)-one and IV-acylureas. J Chem Soc Chem Commun 1225, 1981. 

O-acylisourea species 22 are generated easily by reacting car-bodiimides with a mixture of the desired carboxyUc acid and amine. Then, they undergo aminolysis readily to form the amide and the urea by-product (48). Often, formation of unreactive IV-acylurea 23 by acetyl transfer and racemization are observed (see Fig. 7). This side reaction can be minimized substantially by reacting the acid with the carbodiimides at 0°C before adding the amine or by using DMAP or HOBt 24 as adjuvants (49). 

It has been known for some time that carbodi-imides react with carboxylic acids (a) giving acid anhydrides and ureas, or (b) iV -acylureas. Khorana and Todd have been successful in converting dibenzyl hydrogen phosphate into the pyrophosphate by the following reaction with dicyciohexylcarbodi-imide ... 

In the dicyclohexylcarbodi-imide method of peptide-bond formation, the problems of racemization and rearrangement to A-acylureas can be avoided by interception of the intermediate activated ester with 1-hydroxybenzo-triazole. The ester so produced functions efficiently in amide-bond formation similar beneficial properties have already been noted with iV-hydroxy-succinimide. 

---