Nitro compounds, aliphatic nitronates

Under suitable conditions it is possible to isolate the A-substituted hydroxylamines that are formed as intermediates in the reduction of nitro compounds. For this purpose it is essential in the reduction of aromatic nitro compounds to work with neutral or nearly neutral solutions suitable reducing agents are hydrogen and platinum oxide catalysts in glacial acetic acid,82,83 zinc dust in ammonium chloride solution,84 aluminum amalgam,85 and ammonium sulfide.86 Aliphatic nitro compounds may be reduced as their alkali salts (nitronates) by diborane in tetrahydrofuran, then giving A-alkylhydroxyl-amines 87 for instance, A-cyclohexylhydroxylamine is thus obtained from nitrocyclohexane in 53% yield. However, aliphatic nitro compounds are converted into A-alkylhydroxylamines more simply by catalytic hydrogenation in the presence of palladium-barium sulfate unlike aromatic nitro compounds, aliphatic nitro compounds require an acid medium for reduction to hydroxylamines an oxalic acid medium has proved the most suitable. 

The closely related tributylstannyl nitronates 1120, which can be expected to react in the same way as O-silylnitronates, have been prepared by treatment of aliphatic nitro compounds 1035 with tributylstannylamine 1118 at 24°C or by heating of 1035 with tributylstannyl oxide 1119 in toluene with azeotropic removal of H2O [160] (Scheme 7.49). 

As already discussed in Section 7.4, hexamethyidisiiane 857 (which is produced on a technical scale), in the presence of catalytic amounts of tetrabutylammonium fluoride di- or trihydrate in THF, reduces aromatic heterocyclic N-oxides such as pyridine N-oxide 860, quinoline N-oxide 877, or isoquinoline N-oxide 879 to the heterocycles [95] and nitrones to Schiff-bases. Aromatic nitro compounds such as nitrobenzene are reduced analogously to azo compounds such as azobenzene [96]. As mentioned in Section 7.5, secondary aliphatic nitro groups are reduced to oximes. 

Acylation of the nitronate 9-71 leads to the iminium ion 9-72 which, by the addition of an isocyanide, forms the cation 9-73. Following two acyl group migrations, the compound 9-75 is obtained via 9-74. The best results were obtained when allylic nitro derivatives were used, as these can form the corresponding enolate in the presence of NEt3. Aliphatic nitro compounds could also be employed, but in these cases it was necessary to use the more basic DBU. 

Isoxazolines A-oxides have been synthesized from primary aliphatic nitro compounds and alkenes by a two-step procedure consisting of 1,3-DC of a 1-halo-substituted silyl nitronate followed by halosilane elimination <06S2265>. 

A general method for nitrone formation is based on the interaction of nitro compounds with carbanions. Interaction between nitroso compounds (175) and anions of aliphatic nitro compounds (178) leads to nitrones (179). The source of anions are metal salts of nitro compounds, triethylamines, and trimethylsilylni-tronates (Scheme 2.63) (334, 335). 

Butenylmagnesium chloride converts aromatic nitro compounds 383 (Ar = 2-Me(V I I4. 2- or 4-CIC6H4 or 2.6-Mei(VJ h) into the nitrones 384 aliphatic nitro compounds 385 (R = Pr or C5H11) yield allyl nitrones 386 in this reaction425. 

Reactions of aliphatic nitro compounds with nucleophiles have been reviewed442-444. The oxidative reaction of nitronate anions, e.g. 410, with thiocyanate anions to yield thiocyanates 411 proceeds by a radical radical-anion chain mechanism SrnI (equation 133). Analogous replacements by azide, benzenesulphinate and 4-chlorobenzenethiolate have been reported445. 

A second and related consequence in aliphatic nitro compounds is the acidification of the directly bonded CH unit through the attendant stabilization of the derived conjugate bases (5,6). As with all delocalized anions, reprotonation gives rise to tautomers, the original C-nitro compound (I) and the oci-nitro or isonitro form (II), Eq. 2.1. The aci-nitro tautomers are typically present in very minor concentrations, with equilibrium constants (A eq) between 10 and 10 (7). Alkylation of the delocalized anion leads to both a-substituted nitro compounds and the regioisomeric nitronic esters (nitronates). Nitronates were described as early as 1894 (8), however, the first isolated nitronic ester was obtained several years later upon the addition of diazomethane to phenylazonitromethane (1), Eq. 2.2 (9). 

Nitro compounds are versatile synthetic intermediates which have found widespread utility in industrial applications. Aromatic nitro compounds are the usual starting materials for commercial applications, but aliphatic compounds exhibit a greater diversity of chemical behavior under reducing conditions. " Nitroso compounds, hydroxylamines, oximes, amines, nitrones, ketones and silyl nitronates are frequently encountered during the reduction of nitro compounds. Several specialized reviews have appeared which highlight the versatility of the nitro group in organic chemistry. ... 

Removal of a proton from an aliphatic nitro compound gives a carbanion (R2C —NO2) that can be alkylated at oxygen or carbon. 0-Alkylation gives nitronic esters, which are generally unstable to heat but break down to give an oxime and an aldehyde or ketone. 

Silylation as new strategy of using of aliphatic nitro compounds in organic synthesis (cyclic silyl nitronates, heterocyclization) 01IZV1850. 

Aliphatic nitro-compounds, as their nitronate anions, react with molybdenum peroxide, MoO5.py.HMPA, to give carbonyl compounds. Primary nitroalkanes give the carboxylic acid. A re-appraisal of potassium permanganate as oxidant for primary nitroalkane salts indicates this can be an excellent reagent for the preparation of aldehydes, particularly quaternary aldehydes. ... 

TBDMSCl-Assisted Reactions. Nitro aldol (Henry) reactions have been reported to be promoted by TBDMSCl. To a THF solution of tetra-n-butylammonium fluoride is added sequentially equimolar amounts of the nitro compound, aldehyde, and EtsN, followed by an excess of TBDMSCl (eq 11). Substitution of TMSCl for TBDMSCl reduces the yield of nitro aldol product. The authors speculate that TBDMSCl is responsible for activation of the aldehyde while n-Bu4NF activates the nitro compound. In a related method, primary and secondary nitro alkanes were treated with LDA in THF followed by addition of TBDMSCl to give the corresponding silyl nitronates. The silyl nitronates reacted with a variety of aliphatic and aromatic aldehydes which gave vicinal nitro TBDMS aldol products. ... 

A significant improvement on the C-acylation of nitromethane anion (Vol. 3, p. 175) has been published, and the method extended to reaction with other aliphatic nitro-compounds. Thus, the generality of the reaction of acylimid-azoles with nitronate ions has been established and serves as a synthetic route to a variety of a-nitro-ketones and -esters (Scheme 38). Similarly, the C-carboxylation... 

Lypkalo IM, Ioffe SL, Strelenko Y, Tartakovsky VA (1996) A novel general method for the synthesis of nitrones by reaction of nitroso compounds with anions of aliphatic nitro compounds. Russ Chem Bull 45(4) 856-862. doi 10.1007/BE01431312... 

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