In Situ Formation of N-Trifluoroacetoxy Succinimide (TFA-NHS): One-Pot Formation of Succinimidyl Esters, N-Trifluoroacetyl Amino Acid Succinimidyl Esters, and N-Maleoyl Amino Acid Succinimidyl Esters

• Published in: Journal of organic chemistry Vol. 76; no. 21; pp. 9169 - 9174
• Main Authors: Leonard, Nicholas M, Brunckova, Jarmila
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 04-11-2011
• Subjects: Amino Acids - chemistry; Chemistry; Esters; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics and mechanisms; Molecular Structure; Organic chemistry; Preparations and properties; Reactivity and mechanisms; Stereoisomerism; Succinimides - chemical synthesis; Succinimides - chemistry; One pot reaction; Ester; Imide; Trifluoroacetic acid; Nitrogen heterocycle; Aminoacid; Reaction mechanism; Pyrrolidine derivatives; Optimization
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo201686e

A method for the in situ formation of N-trifluoroacetoxy succinimide (TFA-NHS) and its application in the formation of succinimidyl esters is presented. The developed method provides N-trifluoroacetyl and N-maleoyl amino acid succinimidyl esters from a variety of amino acids using a one-pot, high-yielding protocol. Investigations into the formation of an N-maleoyl amino acid succinimidyl ester supported the proposal of a revised reaction mechanism, and contributed to the optimization of the reaction conditions.