Base-free ester aminolysis

Base-free ester aminolysis An efficient method of amide synthesis by solvent-free ester aminolysis under the action of microwave activation has been described by Toma et al. [119] (Eq. 35) ... 

The most common industrial syntheses of carbamate esters are based on either the alcoholysis of phosgene, followed by aminolysis of the intermediate chlorofor-mate, or the reaction of an alcohol with an isocyanate, usually prepared from COCl2 [6, 7]. The development of phosgene-free routes to carbamates represents an important synthetic challenge, and several synthetic strategies are currently under investigation in this area. 

The azide procedure for peptide synthesis and particularly for fragment condensations is considered to be a mainly racemization free method. This low racemization tendency of azides was explained by several theories, which have been reviewed.t l The most plausible cause of racemization is the formation of oxazoles (Scheme 3) and the related enolization. In presence of bases the a-carbon proton is readily abstracted to form an anionic oxazol-5(4//)-one resonance system.For the formation of the oxazol-5(4//)-one the influence of the substituent Y on the a-carbonyl is essential. Since the a-carbonyl group of amino acid azides are less activated and thus relatively insensitive to oxygen containing nucleophiles such as water and alcohols, oxazol-5(4//)-one formation is largely prevented. It was proposed that the soft electron shell of the azide shields the a-carbonyl atom, so that only strong nucleophiles can attack it.t 1 The reactivity towards amines can be explained in a manner analogous to the aminolysis of anchimerically assisted active esters.h 1... 

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