New Easily Removable Specific Protecting Groups

The Z-group plays an important role even today. The reagent usually applied for its introduction, benzyl chlorocarbonate, C6H5CH2—O—CO—Cl (also 

Sulfur, for instance in cysteine, can poison the catalyst, a disadvantage that prompted attempts to find alternative methods of reduction. The solution of sodium in liquid ammonia offered itself for this purpose. 

A further reagent for the relatively selective removal of the Z-group is a concentrated (33%) solution of hydrobromic acid in glacial acetic acid. This mixture, introduced by Ben Ishai and A. Berger in 1952, removes the benzyloxy-carbonyl group at room temperature within an hour through the catalyzed attack of the Br anion on its benzyl moiety which is converted thereby to benzyl bromide with the liberation of an unstable carbamoic acid (Fig. 9). 

Subsequently in 1959, Friedrich Weygand broadened the possibiUties for the acidolytic cleavage of the Z-group by recommending heating with anhydrous trifluoroacetic acid. In the process instead of benzyl bromide, benzyl trifluoro-acetate forms. 

The cleavage reagent known the longest, a mixture of hydroidodic acid and phosphonium iodide, discovered in E. Fischer s laboratory for the removal of the p-toluenesulfonyl residue (with the formation of thiocresol) and then systematically applied in peptide synthesis by R. Schonheimerin 1926, proved itself effective 

---