Nitro groups, reduction disulfides

Reductive cleavage of disulfides is very easy and can be accomplished without affecting some other readily reducible groups such as nitro groups. 

Alternatively, both peptide chains could be protected at one cysteine residue as a 5-Acm derivative and at the second cysteine residue by an acid-labile [Trt, Mob, Xan, or Bzl(4-Me)], base-labile (Fm), or reduction-labile (5-tBu) group. Both peptide chains may then be separately converted into the free thiol/Acm-protected form for selective activation of one chain as S-SPy or. S -Npys derivatives by reaction with di(2-pyridyl)disulfide or di[5-nitro(2-pyridyl)]disulfide, or as a sulfenohydrazide derivative by reaction with azodicarbocylic acid derivatives for formation of the first interchain disulfide bridge. 

A number of functional groups, such as nitro, diazo, carbonyl, disulfide sulfoxide, alkene, and pentavalent arsenic, are susceptible to reduction, although in many cases it is difficult to tell whether the reaction proceeds enzymatically or nonenzymatically by the action of such biologic reducing agents as reduced flavins or reduced pyridine nucleotides. In some cases, such as the reduction of the double bound in cinnamic acid (C6H5CH=CHCOOH), the reaction has been attributed to the intestinal microflora. Examples of reduction reactions are shown in Figure 7.12. 

A number of functional groups, such as nitro, diazo, carbonyls, disulfides, sulfoxides, and alkenes, are susceptible to reduction. In many cases it is difficult to determine whether these reactions proceed nonenzymatically by the action of biological reducing agents such as NADPFI, NADH, and FAD or through the mediation of functional enzyme systems. As noted above, the molybdenum hydroxylases can carry out, in vitro, a number of reduction reactions, including nitro, azo, A-oxidc, and sulfoxide reduction. Although the in vivo consequences of this are not yet clear, much of the distribution of reductases described below may be, in whole or in part, the distribution of molybdenum hydroxylases. 

This reaction has found little application to mercaptan syntheses since the mercaptans are usually as readily available (by other methods) as the disulfides. The S-S linkage is reduced by zinc in acetic or sulfuric " acid, lithium aluminum hydride, or metallic sodium. y-Hydroxy-propyl disulfide is reduced electrolytically in 70% yield. Reduction by sodium disulfide does not reduce the nitro group in the preparation of p-nitrothiophenol (65%), whereas zinc and acetic acid converts o-nitro-phenyl disulfide to o-aminothiophenol (90%). Disulfides made by the action of ammonium hydrogen sulfide on aldehydes are sources for difficultly available aromatic and heterocyclic mercaptans. The disulfides are reduced by aluminum amalgam and water. ... 

Aminobenzonitrile is prepared by reduction of 3-nitrobenzonitrile by sodium disulfide in aqueous suspension (63%). This reagent causes some hydrolysis of the cyano group. A selective hydrogenation of the more reactive nitro group in the presence of the cyano group can also be done, e.g., in the preparation of p-aminobenzyl cyanide (7S>%). ... 

Sodium borohydride reduces disulfides to thiols, which can then be used to reduce nitro groups. Based on the redox properties of 1,2-dithiolane, lipoamide (17) was used for the selective reduction of mono-substituted nitrobenzenes to the corresponding anilines. Lipoamide (17) can also be immobilized on hydrophilic polymers such as polyvinylamine, polyethyleneimine and chitosan. These polymeric reducing catalysts can be recycled and are easy to separate from the reaction mixture. The system has been used to reduce nitroarenes to anilines. ... 

Dunbrook and Zimmermann 113) report still higher yields, even with short reaction times, when sodium polysulfide and carbon disulfide are used (method C ). The essential appears to be the replacement of the chlorine atom by a mercapto group and the reduction of the nitro group to an amino group, followed by ring closure of the resulting o-aminothiophenol with carbon disulfide to the benzothiazoline-2-thione (method A). 

Reductions. Disulfides are cleaved, and nitroaryl azides are reduced to the amines without affecting the nitro group or other substituents. However, p.y-unsaturated nitroalkenes are reduced to enones, and m-nitrostyrenes give a-allyloxy arylacetaldoximes in the presence of allyl alcohol. ... 

Sulfanylbenzothiazole 3 (2-mercaptobenzothiazole) is produced industrially from l-chloro-2-nitro-benzene, sodium sulfide and carbon disulfide. In this synthesis, nucleophilic substitution of the Cl-atom is followed by reduction of the nitro group and finally by cyclocondensation ... 

Compared to oxidation, EC reduction has not been not widely used with HPLC. Reducible groups include hydroxylamines, nitrosamines, -oxides, peroxides, quinones, aromatic nitro compounds and disulfides. The antibiotic chloramphenicol can be assayed in blood by EC reduction using a mercury film electrode. ... 

At the same time that reduction of the nitro group occurs in NBT SAMs, cross-linking also occurs between adjacent biphenyl groups. This may be exploited to yield micro- and nanostructures. Eck et al. showed that freestanding sheets of cross-linked biphenyls may be formed by electron-induced cross-hnking and released by exposure of the samples to iodine vapor (which oxidizes the S-Au bond). Alternately, NBT SAMs may be cross-linked and the unexposed adsorbates removed by thermal desorption (thiols readily desorb from gold surfaces because the activation barrier for conversion of two thiolates to a disulfide is small). ... 

A mixture of o-nitrobenzyl disulfide (prepn. s. 640), 80%-hydrazine hydrate, and ethanol refluxed ca. 2 hrs. on a water hath o-nitrohenzylidenehydrazine. Y 74.6%.—Reduction of the nitro group did not occur. Also m- and p-isomers s. T. Kametani et al., Ghem. Pharm. Bull. 8, 995 (1960). 

Many other functional groups are reduced by Sml. For example, sulfonyl halides are converted to disulfides. The reduction of nitro compounds by this reagent enables synthesis of 1,2-diamines based on a reaction sequence initiated by nitronate addition to aldimines, and in the presence of nitriles it furnishes amidines, and that of isothiocyanates in the presence of conjugated esters, the half thioamide derivatives of succinic esters. 

Adamantyl sulfides 576 have been prepared by radical decarboxylation of [bis(l-adamantane-carboxy)iodo]benzene 575 (Ar = Ph) in the presence of disulfides 574 (Scheme 3.227). A study of the reactivity of various [bis(l-adamantanecarboxy)iodo]arenes 575 in this reaction has shown that the introduction of strong electron-withdrawing groups, such as nitro and perfluoro, into the aromatic ring of 575 leads to a significant reduction of the yield of product 576, which is explained by the lower reactivity of p-nitro and perfluorophenyl derivatives 575 in radical reactions due to the increased I—O bond strength in these compounds [619]. 

In summary, the reactivity of various functional groups toward Li 9-BBNH is classified into four broad categories [18] (1) rapid- or fast-reduction aldehyde, ketone, ester, lactone, acylchloride, acid anhydride, epoxide, disulfide, -alkyli-odide, and tosylate (2) slow-reduction tertiary amide, alkylbromide, and aromatic nitrile (3) sluggish-reduction carboxylic acid, aliphatic nitrile, primary amide, nitro and azoxy compounds, and secondary alkylbromide and tosylate (4) inert olefin, oxime, alkylchloride, sulfoxide, azo-compound, sulfide, sulfone, and sulfonic acid. 

---