4-Nitrobenzyloxycarbonyl group

Originally, the photoremovable 4,5-dimethyl-2-nitrobenzyloxycarbonyl group (Nvoc, 3) introduced by Patchornik (Scheme 3)bl was utilized for temporary protection of the a-amino group of the growing peptide chain. However, photolysis under optimized conditions (12 min in 5 mM sulfuric acid/dioxane) sometimes causes side reactions and does not always proceed quantitatively. 

The use of the 4-nitrobenzyloxycarbonyl group as protecting group is discussed in Chapter 23. 

Orr/w-nitrobenzyloxycarbonyl group is used as a photolabile linker for the attachment of encoding molecules in combinatorial synthesis of p tides. 

Patchornik et al. have developed the 2-nitrobenzyl-based amino protecting groups 4,5-di-methoxy-2-nitrobenzyloxycarbonyl (Nvoc) and 2-nitrobenzyloxycarbonyl [Z(2-NQ2)], which... 

The use of protecting groups is common in penicillin chemistry the amino function is normally protected by a triryl, benzyloxycarbonyl. p-nitrobenzyloxycarbonyl. tridlloroethyloxycarbonyl. or trimethylsilyl group and the carboxylic acid is usually protected as a benzyl, p-nitrobenzyl. p-methoxybenzyl. or trichloroethyl ester. Acylations may thus be carried out... 

Amino protecting groups fall into four broad categories nitrobenzyl (e.g., nitrobenzyloxy-carbonyl and 4,5-dimethoxy-2-nitrobenzyloxycarbonyl), phenacyl (e.g., 4-methoxyphen-acyloxycarbonyl), benzyloxycarbonyl (e.g., a,a-dimethyl-3,5-dimethoxybenzyloxycarbonyl), and arylsulfonamides (e.g., tosyl). All but the sulfonamides mask the amino group as a carbamate. Removal of the blocking moiety releases an unstable carbamic acid, which spontaneously decarboxylates to give the unprotected amine. 

Protection of amino groups as carboxamides is generally not useful however, ben-zyloxycarbonyl derivatives of primary and secondary amines may be reduced at vitreous carbon cathodes in DMF at very negative potentials, with cleavage to toluene and free amine in good yield (>80%) [174,175]. However, 4-nitrobenzyloxycarbonyl derivatives may be deprotected at 1.2 V (SCE) the cleavage of the initially formed radical anion is slow on the time scale of CV but sufficiently fast for a preparative-scale reduction. 

Figure 17.1 The 6-nitroveratryloxycarbonyl (NVOC) and 2-nitrobenzyloxycarbonyl (NBOC) groups.

Protection of Amines. Reaction of o-NBA with Phosgene yields the stable compound o-nitrobenzyloxycarbonyl chloride (eq 6). Subsequent reaction with 2-amino-2-deoxy-o-glucose cleanly affords the protected amine. The yields of the free amines obtained upon irradiation (eq 7) are lowered by side reactions with the o-nitrobenzaldehyde generated under the reaction conditions. - - Yields are increased by the addition of polymeric aldehydes or sulfuric acid to the reaction mixture during irradiation, or by utilizing the related 2,6-dinitrobenzyl alcohol in the first step. Functional group tolerance for this entire reaction sequence is impressively high. 

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