The preparation and reactions of mixed anhydrides of N-alkoxycarbonylamino acids

Pure mixed anhydrides R 1 OCO-Xxx-O-COOR 2 (Xxx=NHCHRCO) have been obtained by reaction of N-alkoxycarbonyl-amino acids R 1 OCO-Xxx-OH with alkyl chloroformate R 2 OCOCl (R 2  = methyl, ethyl, isobutyl, menthyl) in the presence of N-methylmorpholine or N-methylpiperidine (NMP) in dichloromethane at −5 °C, followed by washing the mixtures with aqueous solutions and removal of the solvent. R 1 OCO-Xxx-O-COOR 2 (R 2  = ethyl, tert-butyl) have been obtained by reaction of R 1 OCO-Xxx-O − • + HNMP with the corresponding dialkyl dicarbonates followed by the same work-up. Mixed anhydride generation is much slower when triethylamine is used as base. The initial reaction in the decomposition of mixed anhydrides is cyclization to the 2-alkoxy-5(4H)-oxazolone (R 1 O-oxazolone) followed by release of alcohol R 2 OH. Symmetrical anhydride (R 1 OCO-Xxx) 2 O and ester R 1 OCO-Xxx-OR 2 are also formed. The ease of cyclization depends on R 2 , and is in the order methylsulfonylethyl (Ms) [Formula: see text] methyl/ethyl/isobutyl [Formula: see text] menthyl. R 1 OCO-Xxx-O-COOMs preparations contained a substantial amount of R 1 O-oxazolone. Attempts to use this reaction as a preparative procedure for obtaining R 1 O-oxazolones failed because they are too sensitive to hydrolysis and react too quickly with the product, forming the symmetrical anhydride. The effect of various parameters on the amount of urethane generated by aminolysis at the carbonate moiety of R 1 OCO-Xxx-O-COOR 2 was examined without the uncertainty that any urethane arose from aminolysis of unconsumed chloroformate.