Studies on the disproportionation of mixed anhydrides of N‐alkoxycarbonylamino acids

• Published in: International Journal of Peptide and Protein Research
• Main Authors: BENOITON, N. LEO, LEE, YOUNG C., CHEN, FRANCIS M.F.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 1993
• Subjects: Syan; Carbonic acid
• Online Access: http://dx.doi.org/10.1111/j.1399-3011.1993.tb00449.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1399-3011.1993.tb00449.x; https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-3011.1993.tb00449.x

Mixed anhydrides from Z‐valine and ethyl, isobutyl, isopropyl and isopropenyl chloroformate, and from N‐tert ‐butoxycarbonyl‐ (Boc) and N ‐benzyloxycarbonyl‐ (Z) leucine and phenylalanine and Boc‐ and N ‐9‐fluorenylmethoxycarbonyl‐valine and ethyl chloroformate were purified and left in dichloromethane at 23°C. The symmetrical anhydride (SyAn) generated after 24 h was determined by normal phase high‐performance chromatography. No SyAn was produced from the anhyrides of Z‐ and Boc‐valine; SyAn was produced from the other anhydrides. Anhydrides examined without isolation generally produced more SyAn than the pure compounds. More SyAn was generated in dimethylformamide and tetrahydrofuran than in dichloromethane, or in the presence of an excess of N ‐methylmorpholine or triethylamine. The anhydride from isobutyl chloroformate was much more stable than the anhydride from ethyl chloroformate. It is suggested that disproportionation of pure mixed carboxylic acid – carbonic acid anhydrides occurs by a bimolecular mechanism.