Nitro compounds with methanol

Hydroxyaminopyridazine 1-oxides are usually formed by catalytic hydrogenation of the corresponding nitro derivatives over palladium-charcoal in methanol, provided that the reaction is stopped after absorption of two moles of hydrogen. 3-Hydroxyaminopyridazine 1-oxide and 6-amino-4-hydroxyamino-3-methoxypyridazine 1-oxide are prepared in this way, while 5-hydroxyamino-3-methylpyridazine 2-oxide and 5-hydroxyamino-6-methoxy-3-methylpyridazine 2-oxide are obtained by chemical reduction of the corresponding nitro compounds with phenylhydrazine. 

Swarts778 in 1922 this amine is prepared by nitrating benzotrifluoride and reducing the nitro compound in methanol catalytically with Raney nickel.779,780 The yield of trifluoroacetic acid amounts to 90-95% if suitable technique is used — apparatus is described in detail by Wachter.781... 

Nitrobiphenyl gave 2-aminobiphenyl, but no carbazole therefore a nitrene intermediate appeared unlikely in this reduction. The reaction between Kj[HFe(CO)43 and aromatic nitro compounds proceeds vigorously and exothermally in alcohol at room temperature to give the corresponding aromatic amines in excellent yields[76j. The reaction is not catalytic and is not affected by reaction atmospherearomatic nitro compounds with Fe3methanol-benzene is catalysed by the crown ether, 18 crown-6, with aqueous K0H[77j, or by PhCH2N3+Cl " with aqueous NaOH[64,78l. 

Nitroso compounds are formed selectively via the oxidation of a primary aromatic amine with Caro s acid [7722-86-3] (H2SO ) or Oxone (Du Pont trademark) monopersulfate compound (2KHSO KHSO K SO aniline black [13007-86-8] is obtained if the oxidation is carried out with salts of persulfiiric acid (31). Oxidation of aromatic amines to nitro compounds can be carried out with peroxytrifluoroacetic acid (32). Hydrogen peroxide with acetonitrile converts aniline in a methanol solution to azoxybenzene [495-48-7] (33), perborate in glacial acetic acid yields azobenzene [103-33-3] (34). 

The Zinin reduction is also usehil for the reduction of aromatic nitro compounds to amines in the laboratory. It requires no special equipment, as is the case with catalytic hydrogenations, and is milder than reductions with iron and acid. Usually ammonium or alkah sulfides, hydrosulftdes or polysulftdes are used as the reactant with methanol or ethanol as the solvent. 

Nucleophilic aromatic substitutions involving loss of hydrogen are known. The reaction usually occurs with oxidation of the intermediate either intramoleculady or by an added oxidizing agent such as air or iodine. A noteworthy example is the formation of 6-methoxy-2-nitrobenzonitrile from reaction of 1,3-dinitrobenzene with a methanol solution of potassium cyanide. In this reaction it appears that the nitro compound itself functions as the oxidizing agent (10). 

Coulometry. Even in water, controlled potential or potentiostatic coulometry is a difficult and often time-consuming technique, as the analyte must participate in a direct electrode reaction. Therefore, in non-aqueous media there are only a few examples of its application, e.g., the potentiostatic coulometry of nitro and halogen compounds in methanol (99%) with graphical end-point prediction, as described by Ehlers and Sease153. 

Hydrogen gas can be replaced by ammonium formate for the reduction of nitro compounds to amines. The ammonium formate method is efficient, and the rapid workup procedure by simple filtration makes it widely used for converting the N02 to the NH2.96 For example, a-nitro esters are reduced to cx-amino esters in excellent yields on treatment with HC02NH4 and Pd/C in methanol.96... 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

However, the character of the reaction of 3-nitro-substituted TV-oxide (169) with the C,C triple bond is changed 371. Apparently, the first step affords the normal cycloadduct A, which is successively rearranged into aziridine B. Elimination of the nitronate anion from the latter compound gives rise to ambident cations C and D, which, after quenching with methanol, form dihydrooxazines (170) or (171) depending on the nature of the substituent R. 

The tetrahydro derivative 47 was obtained from an unexpected cyclization of the nitro compound 46 by deprotonation with NaOMe in methanol followed by a treatment with TiCh, then with H20. This side product was observed in the approach of amathaspiramide F 48 (Equation 4) <2002AGE4556>. 

The bimolecular reduction of aromatic nitro compounds, depending on reaction conditions, may produce azoxy compounds, azo compounds, hydrazo compounds (1,2-diarylhydrazines), benzidines, or amines. Whereas the reduction with zinc and sodium hydroxide leads to azo compounds, zinc and acetic acid/acetic anhydride produces azoxy compounds. Other reducing agents suggested are stannous chloride, magnesium with anhydrous methanol, a sodium-lead alloy in ethanol, thallium in ethanol, and sodium arsenite. 

Conversion of nitro compounds to ketones. This reaction has usually involved reductive or oxidative hydrolysis of the corresponding alkali nilronates. A recent method involves direct oxidation with 30% H202 and K2C03 in methanol at room temperature. Yields are 75-95%. ... 

A variant of the preceding strategy was applied to the total syntheses of ( )-elwesine (439), ( )-epielwesine (449), and ( )-oxocrinine (415) (Scheme 39) 200). This approach featured a new methodology for the construction of substituted tetrahydrobenzazepine ring systems that was based on a two-step Tscher-niac-Einhom-like aromatic amidoalkylation as exemplified by the conversion of 443 to 444. To this end, the unsaturated nitrile 440 was allowed to react with nitromethane in the presence of Triton B, and the intermediate nitro compound was converted to the acetal 441 by reaction with methanolic sodium methoxide followed by concentrated sulfuric acid in dry methanol. Transketalization of 441... 

---