Hydrogenation of nitroalkanes

Examples of the hydrogenation of nitroalkanes to nitroso or hydroxylimio compounds are rather few. On the other hand, more examples are known for the hydrogenation of nitroalkanes to the corresponding hydroxylamines. 

The a-hydrogen of nitroalkanes is acidic (less acidic than those of aldehydes and ketones). The anion is also resonance stabilized. 

In view of its industrial importance, a number of homogeneous catalysts have been examined for use in selective hydrogenations of nitroalkanes to amines.Tris(triphenylphosphine)ruthenium(II) chloride is particularly effective. The mechanism of this hydrogenation is known to involve nitronate anion formation. ... 

The a-hydrogens of nitroalkanes are appreciably acidic due to resonance stabilization of the anion [CH3NO2, 10.2 CH3CH2NO2, 8.5]. The anions derived from nitroalkanes give typical nucleophilic addition reactions with aldehydes (the Henry-Nef tandem reaction). Note that the nitro group can be changed directly to a carbonyl group via the Nef reaction (acidic conditions). Under basic conditions, salts of secondary nitro compounds are converted into ketones by the pyridine-HMPA complex of molybdenum (VI) peroxide. Nitronates from primary nitro compounds yield carboxylic acids since the initially formed aldehyde is rapidly oxidized under the reaction conditions. 

When a mixed catalyst containing silver is used, the hydrogenation of nitroalkanes can be conducted so that reduction stops at the oxime stage this has been studied in detail for nitrocyclohexane.74... 

Nitro groups can be introduced into aliphatic compounds by way of an aldol reaction between the anion of a nitroalkane and an aldehyde or a ketone. The a-hydrogens of nitroalkanes are sufficiently acidic that they are removed by bases such as aqueous NaOH and KOH. The of nitromethane, for example, is 10.2. The... 

Simple ketones and esters are inert. On the other hand, nitroalkanes react smoothly in r-butyl alcohol as a solvent with butadiene, and their acidic hydrogens are displaced with the octadienyl group. From nitromethane, three products, 64, 65, and 66, are formed, accompanied by 3-substituted 1,7-octadiene as a minor product. Hydrogenation of 65 affords a fatty amine 67 which has a primary amino function at the center of the long linear chain[46,61]. 

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

Thus, the reaction of alkyl halides and a-halo esters with sodium nitrite provides a very useful synthetic method for nitroalkanes and a-nitro esters. However, ethyl bromoacetate is exceptional in that it fails to give ethyl nitroacetate on treatment with sodium nitrite.93 This is due to the acidic hydrogen of the ethyl nitroacetate, which undergoes a further reaction with sodium nitrite to give the oxidized products (see Section 6.1, which discusses the Nef reaction). In a similar way, the reaction of benzyl bromide with sodium nitrite at 25 °C gives benzoic acid predominantly. To get phenylnitromethane, the reaction must be carried out at low temperature (-16 °C) (Eq. 2.48).93... 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Some recent advances have been reported in oxime oxidation, including the in situ generation of peroxytrifluoroacetic acid from the reaction of urea hydrogen peroxide complex with TFAA in acetonitrile at 0 °C This method gives good yields of nitroalkanes from aldoximes but fails with ketoximes. 

Nitroalkanols are intermediate compounds that are used extensively in many important syntheses 142). They can be converted by hydrogenation into / -aminoalcohols, which are intermediates for pharmacologically important chemicals such as chloroamphenicol and ephedrine. They are obtained by Henry s reaction by the condensation of nitroalkanes with aldehydes. The classical method for this transformation involves the use of bases such as alkali metal hydroxides, alkoxides, Ba(OH)2, amines, etc. 142-144). However, these catalysts give predominantly dehydrated products—nitroalkenes— which are susceptible to polymerization (Scheme 16). The reaction proceeds by the nucleophilic addition of the carbanion formed by the abstraction of a proton from the nitro compound to the carbon atom of the carbonyl group, finally forming the nitroaldol by abstraction of a proton from the catalyst. 

Scheme 6.54 Chiral nitroalkanes provided from the 54-catalyzed asymmetric transfer hydrogenation of nitroalkenes in the presence of 55.

Hydrogenation catalyst. C,ePd catalyzes hydrogenation of aromatic nitro compounds to anilines and of nitroalkanes to amines (both quantitative). It is also effective for hydrogenation of alkynes to (Z)-alkenes in 90-99% yield, particularly when cthylcnediamine is also present. In fact it is superior to palladium on carbon in the presence of EDA, even though the rate is somewhat slower. 

The most important reactions of nitroalkan.es are those involving the a hydrogens of the primary and secondary compounds. For example, nitro-methane is sufficiently acidic to dissolve in aqueous hydroxide solutions. The anion so produced has an electronic structure analogous to the nitrate anion ... 

In cases where there is strong solvation of the carbanion, as for example hydrogen bonding solvation of enolate or nitronate ions in hydroxylic solvents, the intrinsic barrier is increased further because the transition state cannot benefit significantly from this solvation. This is the reason why AG for the deprotonation of nitroalkanes in water is particularly high, i.e., much higher than in dipolar aprotic solvents, see, e.g., entry 11 versus 15 and entry 13 versus 16 in Table 1. These solvation effects will be discussed in more detail below. 

Catalytic hydrogenation of the title compound to the amine with hydrogen at 5—10 bar is described as hazardous, and an electrochemical reduction process is recommended. See other CATALYTIC NITRO REDUCTION PROCESSES, HYDROGENATION INCIDENTS See related NITROALKANES... 

Significant levels of syn diastereoselectivities (5 1 to 16 1) were observed for all substrates, with the exception of an ortho-chloro-substituted aryl imine, which provided only 2 1 syn selectivity. The catalyst was viable for a variety of nitroalkanes, and afforded adducts in uniformly high enantioselectivities (92-95% ee). The sense of enantiofacial selectivity in this reaction is identical to that reported for the thiourea-catalyzed Strecker (see Scheme 6.8) and Mannich (see Tables 6.18 and 6.22) reactions, suggesting a commonality in the mode of substrate activation. The asymmetric catalysis is likely to involve hydrogen bonding between the catalyst and the imine or the nitronate, or even dual activation of both substrates. The specific role of the 4 A MS powder in providing more reproducible results remains unclear, as the use of either 3 A or 5 A MS powder was reported to have a detrimental effect on both enantioselectivities and rates of reaction. 

The reaction of nitroalkanes and dinitroalkanes with sodium hydrogen telluride gives nitrosoalkane dimers and olefins, respectively.96 The reduction of other nitrogenated species such as hydroxylamines, azides, nitroso, azo, and azoxy compounds can also be performed by using tellurium reagents.6,11,12... 

The appearance of silicon tetrafluoride during an investigation of organic fluorine compounds in glass equipment is generally understood to imply the transient formation of hydrogen fluoride this interpretation should be applied here. An interesting point, not yet fully understood, is the appearance of nitroalkane and carbinol only in the reaction of trityl-difluoramine with excess acid. 

SAFETY PROFILE Moderately toxic by intraperitoneal and subcutaneous routes. Questionable carcinogen. Violent reaction with hydrogen peroxide. The oxide increases the sensitivity of nitroalkanes (e.g., nitromethane, nitroethane, and 1-nitropropane) to heat or detonation. See also COBALT COMPOUNDS. 

The reduction of nitroalkanes to A -monosubstituted hydroxylamines has not been extensively explored. The classical approach involves electrolytic reduction of primary and secondary nitroalkanes. Catalytic hydrogenation and hydride reductions of nitroalkenes also yield hydroxylamine derivatives. 

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