A-nitroketone

Alkali salts of primary nitroparaffins, but not of secondary nitroparaffins, react with acyl cyanides to yield a-nitroketones by C-acylation (27). 

A number of reductive procedures have found general applicability. a-Azidoketones may be reduced catalytically to the dihydropyrazines (80OPP265) and a direct conversion of a-azidoketones to pyrazines by treatment with triphenylphosphine in benzene (Scheme 55) has been reported to proceed in moderate to good yields (69LA(727)23l). Similarly, a-nitroketones may be reduced to the a-aminoketones which dimerize spontaneously (69USP3453279). The products from this reaction are pyrazines and piperazines and an intermolecular redox reaction between the initially formed dihydropyrazines may explain their formation. Normally, if the reaction is carried out in aqueous acetic acid the pyrazine predominates, but in less polar solvents over-reduction results in extensive piperazine formation. 

Nitroacetone (237 g) was generated in dichloromethane-ethyl acetate solution by treating its dicyclohexylamine aci-salt with sulfuric acid. Towards the end of concentration of the solution by rotary vacuum evaporation at 40-50°C, a small explosion occurred. Extreme caution and small scale handling of a-nitroketones are urged [1], If exact neutralisation of the dicyclohexylamine salt had not been achieved, presence of excess sulfuric acid (or of some undecomposed aci-salt) may have reduced the stability of the nitroacetone [2],... 

One-pot syntheses of 1,4-diketones, y-oxoaldehydes, y-ketoesters, and co-oxoalkanoates have been reported by bond cleavage of cyclic a-nitroketones with KOH in methanol and subsequent Nef reaction (Section 6.1) with KMn04 (Eq. 5.16).31... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

The high acidity of a-nitroketones makes it possible to perform the Henry reactions or Michael additions under extremely mild conditions. The reaction proceeds in the presence of catalytic amounts of Ph3P to give the C-C bond formation products under nearly neutral conditions. Thus, 1,5-dicarbonyl compounds78 and a-methylenecarbonyl compounds79 are prepared by the denitration of a-nitroketones, as shown in Eqs. 7.67 and 7.68, respectively. 

Although this method is not a general procedure, being specific for a-nitroketones, it has several merits to avoid the use of toxic reagents such as organotin compounds. Functionalized ketones have been prepared by this denitration reaction, in which functionalized nitroalkanes are used as alkyl anion synthons. For example, 3-nitropropanal ethylene acetal can be used as synthon of the 3-oxo-propyl anion and 1,4-dicarbonyl compounds are prepared, as shown in Eq. 7.88.135... 

The simultaneous denitration-deoxygenation of a-nitroketones is performed on treatment with TsNHNH2 and NaBH4 at 80 °C to give alkanes (Eq. 7.90).137... 

No. Enol silyl ether (eV) a-Nitroketone Time (h) Yield (%)c Time (h) Yield (%) ... 

The facile nitration of a wide variety of ketones with TNM in Table 2 is illustrative of the synthetic utility of enol silyl ethers in facilitating a-substitution of carbonyl derivatives. It is necessary to emphasize here that the development of a strong charge-transfer (orange to red) coloration immediately upon the mixing of various ESEs with TNM invariably precedes the actual production of a-nitroketones in the thermal nitration (in the dark). The increasing conversion based on the time/yields listed in Table 2 qualitatively follows a trend in which electron-rich ESE from 6-methoxy-a-tetralone reacts faster than the relatively electron-poor ESE from cyclohexanone. 

Comments on the thermal nitration of enol silyl ethers with TNM. The strikingly similar color changes that accompany the photochemical and thermal nitration of various enol silyl ethers in Table 2 indicates that the preequilibrium [D, A] complex in equation (15) is common to both processes. Moreover, the formation of the same a-nitroketones from the thermal and photochemical nitrations suggests that intermediates leading to thermal nitration are similar to those derived from photochemical nitration. Accordingly, the differences in the qualitative rates of thermal nitrations are best reconciled on the basis of the donor strengths of various ESEs toward TNM as a weak oxidant in the rate-limiting dissociative thermal electron transfer (kET), as described in Scheme 4.40... 

In a significant addition to the synthesis of 1,2,4-oxadiazoles (Scheme 41), Itoh et al. discovered that the treatment of nitriles with iron(lll) nitrate in the presence of acetone or acetophenone gives the 3-acetyl- or 3-benzoyl-l,2,4-oxadiazoles 260, proposing that enolization and nitration gives an a-nitroketone, which then undergoes an acid-catalyzed dehydration to give the nitrile oxides 259 <2005S1935>. 

Haloalkanes are readily oxidized to the corresponding aldehydes or ketones. The best yields are attained with secondary alcohols and unsaturated hydroxyl groups [5]. a-Nitroketones, which are valuable intermediates in organic synthesis, are... 

Solutions of acetyl nitrate have also been used for the synthesis of a-nitroketones from enol esters and ethers. ° ... 

The addition to alkenes of radicals derived from an a-nitroketone is also catalysed by manganese(III) [30]. During the reaction between a-nitroacetophenone 8 and m-but-2-ene, the stereochemical relationship between the methyl substituents is not preserved. The process terminates with the formation of a nitrone. A related process will generate nitromethyl radicals from nitromethane and these add to benzene to give phenyinitromethane [31],... 

Finally, other a-activated carbonyl compounds such as a-nitroketones have been used successfully in very interesting and novel MCRs. Our group proposed an unprecedented reactivity of a-nitroalkanones towards two-substituted acroleins under aqueous conditions, with participation of water as third component [168]. 

Scheme 64 MCRs from a-nitroketones synthesis of bicyclic macrolactones...

Finally, we must mention a number of reports concerning bis chelates, either mononuclear square planar or trinuclear octahedral, with anionic ligands which bear some resemblance to /3-diketones, namely acetophenone,1592 a -nitroketones,1593,1594 hydroxymethylenecamphor and related ligands.1595-1597... 

A new method for the reductive conversion off-keto- -nitroesters to pyrroles involves the use of formamidinesulfinic acid (thiourea S,S-dioxide) as the reducing agent. <95TL9469> The ester substituent seems to be required since no reaction occurred with simple a-nitroketones. 

Another approach used in the empirical characterization of liquid polarity is the study of the outcome of a chemical reaction. Earle et al. [216] report a preliminary study of the keto-enol tautomerization of pentane-2,4-dione, and create an empirical correlation between the degree of tautomerization and the dielectric constant of molecular liquids. They then predict dielectric constants for a series of ILs based on the observed keto-enol equilibrium the values range from 40 to 50, slightly higher than those of short-chain alcohols. A more detailed study by Angelini et al. [217] considers the tautomerization of a nitroketone complex in a series of five imidazolium-based ILs. The results, parameterized as a linear free energy analysis of the behavior of the equilibrium constant, indicates an overall polarity comparable to that of acetonitrile, consistent with the partitioning and spectroscopic studies referenced above. 

Pyrazines and piperazines are obtained by catalytic reduction of a-nitroketones thus, reduction of l-nitro-2-butanone in the presence... 

The reduction of a nitroketone with H2 and Raney nickel in EtOH directly provided the bridged myosmine (42) (76%), presumably via an intermediate amino ketone which undergoes an intramolecular Schiff base cyclization (Equation (17)) <83JOC492>. 

Ballini, R., Rosini, G., and Zanotti, V. 1983. Denitration of a-nitroketones by treatment of their tosylhydrazones with lithium aluminum hydride new applications of the Henry... 

Nitration of ketones. Direct nitration proceeded poorly and a-nitroketones were obtained in only low yield by use of the enol acetate. ... 

---