Blocking of a-Amino Groups

This opened up the attractive possibihty of incorporating the amino group into an ester of carbamoic acid. In the resulting urethane cleavage of the ester and the ensuing decarboxylation regenerate the free amine  

It was, therefore, an invention of major significance when in 1932 Bergmann and Zervas proposed replacement of the ethyloxycarbonyl group by the benzyl-oxycarbonyl (or carbobenzoxy or carbobenzyloxy , Cbz or Z) group. The latter smoothly undergoes homolytic fission on catalytic hydrogenation. The reaction is concluded with spontaneous decarboxylation  

The recognition (Ben Ishai and Berger 1951) that the benzyloxycarbonyl group is cleaved by acidolysis, particularly by HBr in acetic acid, had a major impact on the development of protecting groups. In the heterolytic fission of the carbon-oxygen bond the benzyl cation plays an important role by facilitating the decomposition of the protonated itermediate  

Neither the lachrimatory effect of benzyl bromide, the by-product of the reaction, nor its ability to alkylate various amino acid side chains should escape attention. 

The classical reagent, HBr in acetic acid, can be replaced by HBr in triflu-oroacetic acid, HBr in liquid SO2 or by liquid SO2 itself. Of course the benzyloxycarbonyl group is rapidly cleaved by liquid HF or by a solution of trifluo-romethanesulfonic acid in trifluoroacetic acid. It should be mentioned that it is removed by the much less aggressive trifluoroacetic acid as well. At elevated temperatures the reaction proceeds fairly rapidly, at room temperature it requires several days for completion. Addition of thioanisole (Yajima et al 1978) greatly accelerates the process 

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Blocking of a-Amino Groups 77 and similar results could be achieved with 4-methylthiophenol,... 

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