Nitrophenylsulfenyl group

HCl, Et20, 6 h, 83-88% yield.Acidic deprotection of the BOC group could not be achieved with complete selectivity in the presence of an MTM ester. The trityl and NFS (2-nitrophenylsulfenyl) groups were the preferred nitrogen protective groups. 

If aqueous conditions are to be avoided, the 2-nitrophenylsulfenyl group can be installed using triethylamine as base in an aprotic solvent. In the example shown in Scheme 8.148. the sulfenamide product 148.2 was converted to the N-sulfenyl imine derivative 148.3 by oxidation with M-chJorosuceinimide.337 After nucleophilic addition of the enofate derived from 2-acetylpyridine, the /erf-butyl ester and 2-nitrophenylsulfenyl groups were removed with trifluoroacetic acid to give the Y-keto-a-amino acid 148.4. 

The 2,4,6-trimethylbenzyl ester has been prepared from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 12 h, 60-80% yield) it is cleaved by acidic hydrolysis (CF COOH, 25°, 60 min, 60-90% yield 2 N HBr/HOAc, 25°, 60 min, 80-95% yield) and by hydrogenolysis. It is stable to methanolic hydrogen chloride used to remove A-o-nitrophenylsulfenyl groups or triphenylmethyl esters. ... 

L Zervas, D Borovas, E Gazis. New methods in peptide synthesis. I. Tritylsulfenyl and o-nitrophenylsulfenyl groups as N-protecting groups. J Am Chem Soc 85, 3660, 1963. 

Introduction of the o-nitrophenylsulfenyl group is simple using commercially available 2-nitrobenzenesulfenyl chloride (mp 74-76 C) and aqueous base... 

Further work with diphenylmethyl, phenacyl, and p-methylthioethyl 5 esters disclosed useful combinations with K-protecting groups, particiilarly trityl and o-nitrophenylsulfenyl groups. 

Protection of amino group. The o-nitrophenylsulfenyl group has been used for protection of side-chain amino groups in peptide synthesis. The classical method for removal is treatment with acid, even acetic acid, but this method is not selective. The selective removal is now possible by cleavage with 2-mercapto-pyridine (2-thiopyridone) and 1 equiv. of HOAc in CH3OH, DMF, or CH2Cl2. ... 

Figure 7. Modifications of indole groups (a) HNBB or Koshland s reagent (b) photooxidation (c) 4-nitrophenylsulfenyl chloride.

Protection of thiols.1 The f-butyl group has been of limited service for protection of thiols because removal has involved rather drastic treatment with liquid HF. /-Butyl thioethers can be cleaved by treatment with o-nitrobenzene-sulfenyl chloride in acetic acid at 25° to give S-o-nitrophenylsulfenyl derivatives. These products are reduced to thiols with NaBH4, HSCH2C02H, or HOCH2CH2SH. 

The o-nitrophenylsulfenyl protective group proved very satisfactory in a large-scale synthesis of L-leucyl-L-methionine amide an added advantage was that on cleavage of the protective group the reagent could be recovered readily and used itgain. 

Deblocking cysteine protecting groups. The common S-protecting groups can be cleaved by reaction with 2-nitrophenylsulfenyl chloride in acetic acid followed by reduction of the S-(2-nitrophenylsulfenyl)cysteine residues (equation I). 

Selective removal of o-nitrophenylsulfenyl N-protective groups NSAr NH... 

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