Reaction of Nα-acetyl-L-histidine with diazomethane: A model esterification reaction of carboxylic groups in the presence of imidazole rings

Abstract

The reaction of Nα-acetyl-L-histidine with diazomethane was studied in order to analyze the esterification reaction of a carboxylic group in the presence of an imidazole ring. The reaction produced the expected Nα-acetyl-L-histidine methyl ester (1) as a major product. However, important amounts of [S]Nα-acetyl-1-methylimidazole-4-alanine methyl ester (2) and [S]Nα-acetyl-1-methylimidazole-5-alanine methyl ester (3) were also produced. These compounds, which could be detected by capillary electrophoresis (HPCE) and thin layer chromatography, were fractionated by column chromatography and identified by gas chromatography coupled with mass spectrometry (GC-MS), and ¹H and ¹³C nuclear magnetic resonance spectroscopy. Structures for compounds 1-3 were confirmed by HPCE after acid hydrolysis. These results indicated that the use of diazomethane produces the methyl derivative of the heterocyclic ring in addition to the methyl ester. This reaction should be considered when preparing derivatives for GC-MS analysis.