4- benzyl esters, to protect carboxyl groups

Protection of carboxyl groups, p-Chlorobenzyl esters are about twice as Stable as benzyl esters to hydrolysis by trifluoroacetic acid in methylene chloride at 45°. They can be removed by liquid HF at 0°. These esters are recommended for protection of the P- and y-carboxyl group of aspartic acid and glutamic acid in the synthesis of moderate-sized peptides. 

For protecting carboxyl groups, methyl esters (OMe), ethyl esters (OEt), benzyl esters (OBZL), p-nitrobenzyl esters (ONB), /-butyl esters (OBut) or substituted hydrazides (e.g., —N2H2—Z) are used. Coupling occurs according to the azide method. 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

Section 27 16 Carboxyl groups are normally protected as benzyl methyl or ethyl esters Hydrolysis m dilute base is normally used to deprotect methyl and ethyl esters Benzyl protecting groups are removed by hydrogenolysis... 

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

Benzyl esters of carboxylic acids are frequently used in organic synthesis for the protection of carboxyl groups. The C-O bond in benzyl esters can be cleaved more easily than the corresponding benzyl ether bond. The hydrogenolysis of an ester leads to carboxylic acid and toluene. Examples of debenzylation of benzyl esters of carboxylic acids on Pd/C catalysts are summarized in Table 4.4. 

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