Nitrocyclohexanes

When cyclohexane is nitrated to produce nitrocyclohexane [1122-60-7] the foUowiag techniques minimise undesired C—C breakage ia the ring low temperature nitrations with NO2 (31), carefiil control of the reactor temperatures, and use of halogen additives. Oxygen iacreases the level of C—C bond breakage. 

The only other nitroparaffin manufactured on a large scale was nitrocyclohexane [1122-60-7] made by Hquid-phase nitration of cyclohexane. Nitrocyclohexane was the starting material for S-caprolactam via reduction to cyclohexanone oxime. This process has been superseded by other, more efficient processes (see Caprolactam). Nitrocyclohexane is not being produced ia large quantities for either captive use or sale. 

Double Michael addiQoas of rutro compounds beanng tethered acidic carbons to 3-butyn-3-one under NaH catalysis give nitrocyclohexanes v/ith high stereoselectivity The products are transformed into rrruii -fused bicyclic compounds via the Dickmarm reaction on treatment with base fEq 4 139 ... 

Barco and coworkers have reported a more elegant synthesis of the nitrocyclohexan the double Michael addidon of nltromethane with enones. fEq. 4.130. ... 

Primary aliphatic nitro compounds can be reduced to nitriles with sodium dihydro(trithio)borate " or with f-BuN=C/BuN=C=0. Secondary compounds give mostly ketones (e.g., nitrocyclohexane gave 45% cyclohexanone, 30% cyclohexanone oxime, and 19% A-cyclohexylhydroxylamine). Tertiary aliphatic nitro compounds do not react with this reagent. See also 19-41. 

Whereas secondary nitroalkanes such as 1-nitrocyclohexane 1766 are reduced to the corresponding oximes, for example 1767 [24], primary nitro compounds such as a-nitro-o-xylene 1768 or unsaturated nitro compounds such as 1770 are transformed into nitriles such as 1769 and 1771 [24] (Scheme 12.6). 

The kinetics and mechanisms of the MnO oxidations of nitrocyclohexane and nitrocyclopentane are entirely similar . The combined rate data for solutions at 0.5 M ionic strength are... 

Chiral multiple-coupling reagents have been prepared in enantiomerically pure form by enantio-selective saponification of diesters of meso-2-nitrocyclohexane-l,3-diols (Eq. 3.44) with pig liver esterase (PLE).69... 

Nixan [Nitrocyclohexane] A process for making cyclohexane oxime (an intermediate in the manufacture of nylon) from benzene by liquid phase nitration, followed by hydrogenation of the nitrobenzene. Invented by Du Pont and operated from 1963 to 1967. 

Nitroalkenes are good candidates for the rhodium-catalyzed asymmetric 1,4-addition of organoboronic acids. Hayashi et al. reported that the reaction of 1-nitrocyclohexene with phenylboronic acid in the presence of rhodium/ -BINAP catalyst gave 99% ee of 2-phenyl-1-nitrocyclohexane (Scheme 38).117... 

In addition to the present method,2 1-amino-1-methylcyclo-hexane has been synthesized by the following procedures Ritter reaction, e.g., with 1-methylcyclohexanol (76%, 67%)3i 4 or 1-methylcyclohexene (35%,) 4 5 Hofmann reaction with 1-methyl-cyclohexanecarboxamide (80% as hydrochloride) 6 reduction of 1-methyl-l-nitrocyclohexane (63%) 6 Schmidt reaction with 1-methylcyclohexanecarboxylic acid (42%).6... 

In a recent application of this strategy, nitrocyclohexane 143 (prepared from nitrosugar 142 by intramolecular Henry reaction) was subjected to a radical denitration by HSnBu3, after protection of the hydroxyl groups to avoid side reactions. Inositol 146 was selectively obtained in good yield, once the hydroxyl protecting groups were removed (Scheme 45).101... 

The potassium salts of nitro compounds, such as 2-nitropropane, nitrocyclohexane and ethyl w-nitroacetate, are halogenated at the -position by /V-chloro- or N-bromosuccinimide, e.g. equation 127416. 

Treatment of aromatic nitro compounds with allylmagnesium chloride, followed by 1.4 equiv. of LiAlH LAH) and a trace of palladium on charcoal affords hydroxylamines 387 (Ar = Ph, 4-CIC6H4, 2-FC6H4 or 3-MeOC6H4). If the amount of LAH is increased to 2.5 equiv. iV-allylarylamines 388 result. 1-Nitrohexane and nitrocyclohexane react analogously426. 

Nitrocyclohexane is also reduced to cyclohexylamine with a yield of 62%. 

For the cyclization of dialdehydes, however, its utility seems limited. Being a nitromethane addition product, it can readily undergo retro-nitromethane addition with alkali to give formaldehyde and nitromethane. Thus, it is not surprising that reaction of glutaraldehyde with 2-nitroethanol under the usual conditions (i.e. 1 molar equivalent of sodium hydroxide in aqueous ethanol) should yield 2-nitrocyclohexane-1,3-diol 5), a nitromethane cyclization product With catal5dic amounts of sodium hydroxide (pH 8—9), however, 1-hydroxymethyl-l-nitro-cyclohexane-2-6-diol (80) can be isolated in yields of 24—29%... 

Reaction of 1-nitropropane with glutaraldehyde in aqueous ethanol in the presence of sodium hydroxide yields a mixture of two products, the major component of which, lr-ethyl-l-nitrocyclohexane-2c,6f-diol (98), can be isolated in 36% yield ). Acid-catalyzed acetylation converts (98) into the di-O-acetate, hydrogenation yields the corresponding amine, which has been characterized as the hydroacetate, N-acetate and triacetate. Configurational assignments followed from NMR data, which clearly showed the steric non-equivalence of the two hydroxyl groups vicinal to the tertiary center. 

On treatment of glutaraldehyde with 2-hydroxy-3-nitropropionic acid, only 2-nitrocyclohexane-l,3-diol could be isolated in 10% yield, indicating that, under the conditions used, a retro-aldol degradation takes place with liberation of nitromethane. However, when using methyl 2-methoxy-3-nitropropionate, which cannot undergo a retro-nitro-methane addition", products (101) and (102) are obtained in yields of 7 and 13% respectively... 

Pig liver esterase (PLE, E.C. 3.1.1.1) is one of the most successful enzymes for the enantiotopos-differentiating hydrolysis of dicarboxylic diesters and diacetates of diols as exemplified by the two examples, dimethyl cv. y-4-cydohexene-l,2-dicaiboxylate (I)100 - " 2 and (l/ ,2.S,3S)-l,3-di-acetoxy-2-nitrocyclohexane (3)113. The monoester 2 is obtained with the same results when prepared on a 100 mol scale114. The ee values of the monoester 2 may be determined conveniently by H-NMR spectroscopy in the presence of (+)- or ( )-ephedrine and that of the monoacetate 4, after conversion to the corresponding Mosher ester, by 19F-NMR spectroscopy. 

Of the miscellaneous solvents investigated, nitrocyclohexane and Tetralin look promising for concentrated DDT solutions. Because nitrocyclohexane is not commercially available, only Tetralin represents a practical DDT solvent. 

Primary aliphatic nitro compounds can be reduced to nitriles with sodium di-hydro(trithio)borate.584 Secondary compounds give mostly ketones (e.g., nitrocyclohexane... 

In 70 % HF/pyridine. maintained at — 70 C in a polyethylene flask, was dissolved nitronium tetrafluoroborate (14 g. 0.1 mol). Cyclohexene (4.2 g. 0.05 mol) was added to the solution with stirring over 10 min at — 70 C. The mixture was then w armed up to 0 C over 10 min stirring was continued for 1 h at 0°C. The mixture w as poured into ice water and extracted with Et20. The ethereal layer was washed with H20, aq NaHCOj. H20 again, and dried (Na2S04). After evaporation of the solvent, the residue was distilled and l-fluoro-2-nitrocyclohexane was obtained yield 5.1 g (70%) bp 50 C/3 Torr. 

---