Sulfides, P-nitro

Nitro sulfides are conveniently prepared by simply mixing carbonyl compounds, nitroal-kanes, and thiols in the presence of triethylamine.2 P-Nitro sulfide, which is used for synthesis of rf-biotin, is prepared by this procedure (Eq. 4.2).3... 

Treatment of P-nitro acetates with thiols in the presence of base is also a simple method for the preparation of P-nitro sulfides (Eq. 4.3).4... 

The base-catalyzed joint reaction of nitroalkenes with thiophenol in the presence of aldehydes gives y-phenylthio-P-nitro alcohols in one pot (Eq. 4.5).8 The joint reaction of nitroalkenes with thiols and a,p-unsaturated nitriles (or esters) has also been achieved. (Eq. 4.6).9 P-Nitro sulfides thus prepared show unique reactivity toward nucleophiles or tin radicals. The nitro... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

Tin radical-induced elimination from P-nitro sulfones or P-nitro sulfides proceeds in a stereoselective way to give anti elimination products.153 When diastereomers of P-nitro sulfones can be separated, each diastereomer gives ( )- and (Z)-alkenes selectively (Eq. 7.111). Such... 

Stereoselective preparation of ( )-allyl alcohols via radical elimination from anti-j-phenylthio-P-nitro alcohols has been reported.154 The requisite anti-P-nitro sulfides are prepared by protonation of nitronates at low temperature (see Chapter 4), and subsequent treatment with Bu3SnH induces anti elimination to give (E)-alkenes selectively (see Eq. 7.112). Unfortunately, it is difficult to get the pure yyw-P-nitro sulfides. Treatment of a mixture of syn- and anti-P-nitrosulfides with Bu3SnH results in formation of a mixture of (E)- and (Z)-alkenes. 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

S times more efficient The rate difference is greater for substrates of loiiger acyl chains. Table 6—1 lists the second-order rate constant of the reaction of p-nitro-phenyl c roate (6, PNPC) with several polyethyleneimines. The reactivity of the amino group inaeases by SO times when 10% lauroyl groups are introduced. The reactivity of the SH group incorporated by the reaction of polyethyleneimine with ethylene sulfide 5 is about 100 times greater than those of small-molecule thiols. 

Quinoxaline-2-thione is readily converted into 2-hydrazinoqmnoxaline on treatment with hydrazine hydrate, and 3-hydrazinoquinoxaline-2-thione is readily hydrolyzed (2.5 M HCl at 70°) to quinoxaline-2,3-dione. The sodium salt of quinoxaline-2-thione has been S-alkylated with a wide range of alkyl halides to give 2-quinoxalinyl sulfides,but attempts to carry out a parallel reaction with p-nitrochlorobenzene failed. p-Nitrophenyl-2-quinoxalinyl sulfide (5) can however be prepared by reaction of 2-chloroquinoxaline with the sodium salt of p-nitro-benzenethiol. ... 

The operation is started by pumping up sufficient wash water from previous charges to cover the paddles of the agitator. The stirrers operating at 40 rpm are then started, and 1,000 lb of iron borings is slowly put into the tub. Then 100 lb of 20 B6 hydrochloric acid is added and the mixture agitated and heated until the iron is etched and a good paste of ferrous chloride is made. It should react immediately and distinctly when spotted with a weak sodium sulfide solution. Either dry or moist p-nitro-... 

Toward the end of the run, the reaction slows down, and it is necessary to introduce steam to carry on and complete the reduction. The test for soluble iron also becomes less distinct. As long as there is any p-nitro- aniline present, a yellow spot test will be obtained on filter paper. p-Phen-ylcnediamine yields a purple spot with a perfectly clear ring around the sludge spot. It is always advisable to test for soluble iron with sodium sulfide to ensure completeness of reduction. If the reduction is not carried on at the boiling temperature, intermediate azo and hydrazo products are sure to be formed. These are not so easily reduced and cause a lowering of the yield. 

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]. 

Hydrogenation of o-, m-, and p-nitro chlorobenzenes Pt/C-sulfided Chloroanilines, intermediates in pharmaceuticals and dyes Kosak (1980)... 

B. 2,4-Dinitrobenzenesulfenyl chloride. Dry 2,4-dinitrophenyl benzyl sulfide (232 g., 0.80 mole) and 400 ml. of dry ethylene chloride are placed in a 2-1., one-necked, round-bottomed flask equipped with a stirrer (Note 3). Sulfuryl chloride (119 g., 0.88 mole) (Note 4) is added to the resulting suspension at room temperature. A mildly exothermic reaction causes the solid to dissolve quickly, usually within 1 to 2 minutes, with a temperature rise of 10-15° (Note 5). The resulting clear yellow solution is concentrated to an oil by heating under aspirator vacuum on a steam bath (Note 6). Caution Do not heat with gas or electricity because the product, like many nitro compounds, can explode if overheated.) The residual oil is cooled to 50-60°, and 3-4 volumes of dry petroleum ether (b.p. 30-60°) are added with vigorous handswirling. The oil quickly crystallizes. The mixture is cooled to room temperature and filtered to separate 2,4-dinitrobenzene-sulfenyl chloride as a yellow crystalline solid. The sulfenyl chloride is washed well with dry petroleum ether and dried at 60-80° (Note 7) weight 150-170 g. (80-90%) m.p. 95-96° (Notes 8, 9). 

Similar reducing effects are obtained from alkali sulfides, hydrosulfides and polysulfides [241]. A peculiar reaction believed to be due to sodium polysulfide formed in situ by refluxing sulfur in aqueous-ethanolic sodium hydroxide is a conversion of p-nitrotoluene to p-aminobenzaldehyde [242]. Oxidation of the methyl group by the polysulfide generates hydrogen sulfide which then reduces the nitro group to the amino group. 

It was later shown by Laurence and coworkers that there are significant systematic differences between P values of solvents obtained with indicators with an oxygen donor atom and those with a nitrogen donor atom (Nicolet and Laurence 1986). These authors recommended the use of a single indicator, preferably 4-nitrophenol relative to 4-nitroanisole or else 4-nitroaniline relative to 4-nitro-N,N-di/rae%>/aniline (rather than 4-nitro-N,N-die// y/aniline used by Kamlet and Taft 1976), to establish a basicity scale. The main point of difference is with respect to solvents that do not have an oxygen donor atom, such as amines, pyridines, and sulfides. In order to save the P scale, Kamlet and Taft proposed a family-dependent covalency parameter, equal to -0.20 for P=0 bases, 0.00 for C=0, S=0, and N=0 bases, 0.20 for -O-bases, 0.60 for pyridines, and 1.00 for amines, for use in linear free energy relationships (Kamlet etal. 1985). 

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