Carbonyl compounds from nitroalkanes

The nitroso compound could be directly observed in the reduction of t-nitro-butane at potentials less negative than -1.0 V (SCE) for primary and secondary nitroalkanes, the isolation of carbonyl compounds from the reduction constitutes indirect evidence ... 

Reduction in acid solution of nitroalkenes prepared from carbonyl compounds and nitroalkanes has been employed for the synthesis of oximes and carbonyl compounds [30-32] with a longer carbon chain. 

Manganese(III) can oxidize carbonyl compounds and nitroalkanes to carboxy-methyl and nitromethyl radicals [186]. With Mn(III) as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [186, 187). Further Mn(III)-mediated anodic additions of 1,3-dicarbonyl and l-keto-3-nitroalkyl compounds to alkenes and alkynes are reported in [110, 111, 188). Sorbic acid precursors have been obtained in larger scale and high current efficiency by a Mn(III)-mediated oxidation of acetic acid acetic anhydride in the presence of butadiene [189]. Also the nitromethylation of benzene can be performed in 78% yield with Mn(III) as electrocatalyst [190]. A N03 radical, generated by oxidation of a nitrate anion, can induce the 1,4-addition of aldehydes to activated olefins. NOj abstracts a hydrogen from the aldehyde to form an acyl radical, which undergoes addition to the olefin to afford a 1,4-diketone in 34-58% yield [191]. 

Chlorination. Amides and carbamates undergo iV-chlorination by NaCl-Oxone. Under the same conditions, oximes afford a-chloro nitroalkanes. - When the chlorine source is absent, regeneration of carbonyl compounds from oximes and hydrazones occurs. ... 

The majority of recent contributions for the conjugate addition of C-H acids to a,p-unsaturated carbonyl compounds catalysed through iminium ion intermediates have come from the laboratories of Jprgensen. The ease with which 1,3-dicarbonyl compounds and nitroalkanes can be deprotonated, together with the soft nature of the nucleophile mean this is a particularly facile reaction which conveniently leads to useful precursors for further synthetic manipulation. 

Since hydrocarbon subunits (methyl, methylene and methine groups) are not polarized to a great extent, their nature can be defined by a polar substituent. The high acidity of the a-hydrogen atoms of carbonyl compounds, nitriles, sulfones, and nitroalkanes follows from polarity alternation, the carbon atoms being a donor next to the acceptor substituent. 

Oxidation with potassium permanganate of the nitronate salts to yield carbonyl compounds has been discussed in Section 5.7.7, p. 599 the method is very suitable for the preparation of ketones from secondary nitroalkanes and the experimental details may be readily adapted from Expt 5.84. 

The oxidation of oximes offers an attractively simple route to nitroalkanes from carbonyl compounds. The most effective reagent is pertrifluoroacetic acid in acetonitrile in the presence of sodium hydrogen carbonate as a buffer. Yields are improved by the addition of small quantities of urea to remove oxides of nitrogen. The reaction is illustrated by the conversion of dipropyl ketoxime into 4-nitroheptane (Expt 5.190). 

Protonation of the anion of the aci form, the nitronate anion, takes place at the highest rate on the oxygen the aci form is unstable and either tautomerizes to the nitroalkane or is hydrolyzed to a carbonyl compound and N2O. The reduction of an aci nitro compound, prepared from the anion, is thus generally difficult to study, but its polaro-graphic behavior can be investigated during the reduction of a-halonitroalkanes. 

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. 

The first examples of the conversion of nitroalkanes to carbonyl compounds were described in 1893 by Konovaloff, who was examining the reactivity of nitroalkanes obtained from nitration of alkanes with nitric acid.1 Konovaloff reported that treatment of 2-nitrohexane (3) with strong soda (NaOH) followed by reaction with Zn/HOAc afforded a mixture of methyl butyl ketone (4) and 2-aminohexane (5). Additionally, the reaction of the potassium salt of 2-phenylnitroethane with dilute aqueous acid provided mixtures of acetophenone and 2-phenylnitroethane. 

An interesting variant is the multicomponent synthesis of pyrroles from carbonyl compounds, primary amines, and nitroalkanes first described by Ishii et al. 

A more traditional reaction is the condensation of nitroalkanes with carbonyl compounds (Henry reaction). Nitroaldol products can be isolated but are more commonly oxidised or dehydrated. The nitroaldol products formed from methyl-8-nitrooctanoate and aldehydes, in the presence of Amberlyst A21 resin, were oxidised with... 

Nitroalkanes can be converted to carbonyl compounds in acceptable yields using vanadium(ii) chloride in aqueous dimethylformamide. Treatment of nitroalkanes with acylcarbonylferrate(o) gives a new synthetic route to amides. JViV -Disub-stituted ureas have been prepared, by the same workers, from nitroalkanes (and arenes), bromomagnesium alkylamides, and pentacarbonyliron. The catalytic hydrogenation of nitrosoalkane dimers is a useful route to symmetrical azoxy-alkanes. ... 

A good example of behaviour of this kind is provided by the ionization of carbonyl compounds (equation 6), to which additional data for proton transfer from nitroalkanes to various bases may be added [13, 14]. The isotope effect on these reactions rises to a maximum of 10 at AG° = 0, just where the Bronsted exponent is one-half, and it falls off to considerably lower values on either side of this point. The endothermic side of AG° = 0 is particularly well documented here kyjk-o drops to about 3 when AG° 25 kcal mole" and the Bronsted exponent becomes ca. 0.9. Aromatic hydrogen exchange shows a similar correspondence between isotope effect [15] and Bronsted exponent [16], and additional examples may be found in the hydrolysis of vinyl ethers [17] and diazocompounds [18], as well as in the diazo-coupling reaction [19]. 

It is convenient, for the purpose of seeing how this difference in charge type operates, to view the aromatic protonation reaction in the reverse direction. The process then becomes, just like the ionization of a nitroalkane or of a carbonyl compound, a proton transfer from saturated carbon situated next to some group Z into which the electron pair left behind can delocalize (equation 11). In the reaction... 

Aromatic and heteroaromatic nitroalkenes 353 gave the nitroalkanes 354 [521] in excellent yields. From oximes [522] chiral amines were obtained [308], whereas hydra-zones were hydrolyzed to the corresponding carbonyl compounds [523]. 

Other compounds with reactive methylene and methyl groups are completely analogous to the nitroalkanes. Compounds with ketonic carbonyl groups are the most important. Their simplest representatives, formaldehyde and acetone, were considered for many decades to be unreactive with diazonium ions until Allan and Podstata (1960) demonstrated that acetone does react. Its reactivity is much lower, however, than that of 2-nitropropane, as seen from the extremely low enolization equilibrium constant of acetone ( E = 0.9 x 10-7, Guthrie and Cullimore, 1979 Guthrie, 1979) and its low CH acidity (pK = 19.1 0.5, Guthrie et al., 1982). ... 

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. 

Nitro groups can be added to organic molecules through an aldol reaction between the anion of a nitroalkane and an aldehyde or ketone carbonyl. Intramolecular aldol reactions can be used to create five- or six-membered rings from dicarbonyl compounds (either aldehydes or ketones), which form in preference to smaller or larger rings that may be possible. 

We review in this chapter the nature of the photodecomposition pathways of several of the major products of atmospheric oxidation of the hydrocarbons, namely, the acyclic aldehydes in section IX-B the aldehydes containing additional functional groups in section IX-C the acyclic ketones in section IX-D the cyclic ketones in section IX-E the ketones containing additional functional groups in section IX-F the acyl halides and carbonyl halides in section IX-G nitrous acid, the alkyl nitrites, the nitroalkanes, and the nitroso-compounds in section IX-H nitric acid and the alkyl nitrates in section IX-I the peroxyacyl nitrates in section IX-J the alkyl hydroperoxides in section IX-K and some oxygenates derived from the aromatic hydrocarbons in section IX-L. 

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