A comparative study of the preparations of p-nitrophenyl and n-hydroxysuccinimido tert-butyloxycarbonyl amino acid esters, and synthesis of carboxamide protected isoasparagine and glutamine derivatives

Abstract

This investigation was aimed at the synthesis of two new potential protecting groups for the carboxamide side chain of the asparagine and glutamine. A comparative study of preparations of p-nitrophenyl and N-hydroxysuccinimido tert-Butyloxycarbonyl amino acid esters was carried out. The synthesis of 4-methoxy~-methylbenzylamine and 3-methylbenzhydrylamine precursors for the carboxamide protecting groups was attempted. The 4-methoxy- 2-methylaniline was diazotized and Sandmeyer reaction was utilized to obtain 4-methoxy-Z-methylbenzonitrile. This nitrile was reduced with lithium aluminium hydride to give 4-methoxy-Z-methylbenzylamine. The synthesis of m-bromotoluen was carried out by acetylating ptoluidine, followed by bromination and the removal of ,: the acetyl group by hydrolysis, diazotization, and replacement o£-NZ with hydrogen. Grignard reagent, 3-methylphenyl magnesium bromide, was prepared in anhydrous ether solution from. magnesium turnings and the m-bromotoluene. The 3-mehylpnenyl magnesium bromide was coupled with benzonitrile followed by acid hydrolysis to give 3-methylbenzophenone. The synthesis of 3-methylbenzhydrylamine from the 3-methylbenzophenone by the Leuckart reaction was unsuccessful