Nitrile-N-oxides

Hi) Preparation of isoxazoles from nitrile N-oxides The reaction between a nitrile //-oxide and an alkyne is so facile that it is usually sufficient to leave an ether solution of the reactants at room temperature to obtain the desired isoxazole in good yield. The reaction is in general sensitive to the size of the substituent on the alkyne but not on the nitrile -oxide. In the case of poorly reactive alkynes, the difficulty may be overcome by generating the nitrile -oxide in situ and keeping its concentration low. 

On the whole, the cycloaddition of alkynes to nitrile N-oxides is one of the most important routes to isoxazoles, but in spite of its potentially wide application, its synthetic utility is less than that of the corresponding reaction with alkenes for the following reasons. (1)... 

Table 14 Isoxazoles from Nitrile N-Oxides and C=C Dipolarophiles...

Nitroisoxazoles have been synthesized by reaction of l-chloro-2-nitroethylene with nitrile N-oxides (75C350). 

Thermochemical parameters of some unstable nitrile oxides were evaluated using corresponding data for stable molecules. Thus, for 2,4,6-trimethylbenzo-nitrile N-oxide and 2,4,6-trimethoxybenzonitrile N-oxide, the standard molar enthalpies of combustion and sublimation at 298.15 K were measured by static-bomb calorimetry and by microcalorimetry, respectively, this made it possible to derive the molar dissociation enthalpies of the N—O bonds, D(N—O) (17). 

An unusual solvent effect was observed in cycloadditions of aromatic nitrile N-oxides with alkyl-substituted p-benzoquinones in ethanol-water (60 40) the reaction rates were 14-fold greater than those in chloroform (148). The use of ion pairs to control nitrile oxide cycloadditions was demonstrated. A chiral auxiliary bearing an ionic group and an associated counterion provides enhanced selectivity in the cycloaddition the intramolecular salt effect controls the orientation of the... 

Irradiation of 1-methyl-2-nitrocyclohexene 200 in benzene in the presence of methyl acrylate showed a dual pathway to give both isoxazoline 201 (54%) and the C-nitroso dimer 202 (22%)118 (equation 96). The isoxazoline 201 arose from an excited-state intramolecular cyclization and scission to give a nitrile N-oxide which is trapped by the acrylate. Concurrently, the photoinduced nitro-nitrite inversion also occurs competitively to give the C-nitroso compound which is isolated as the dimer 202. 

Both 4,5-dimethylisoxazole and 3,4-dimethylisoxazole are formed on treatment of the sodium derivative of a - methy lacetaldehyde with hydroxylamine hydrochloride. The two isomers can be separated by fractional distillation (62HC(17)1, p. 54). 4,5-Dialkylisoxazole or 3,4-dialkylisoxazole can be obtained as the sole reaction product from an appropriate nitrile N-oxide and an appropriate vinyl acetate. 

In contrast to this imide-based synthesis, amides of the type RC(0)NH2 are decarbonylated to primary amines (RNH2) with chlorine in the presence of base. This process, often called the Hofmann reaction, involves an intermediate isocyanate (R-N = C = 0) (Fieser and Fieser, 1961 Sandler and Karo, 1983). Aromatic oximes, lacking an a-hydrogen, react with chlorine to form intermediates that are converted to nitrile Af-oxides with base. (Nitrile N-oxides are highly reactive species.)... 

In more detailed accounts, a range of aromatic and aliphatic nitrile N-oxides, prepared in situ by reaction of the corresponding hydroxamoyl chloride with triethylamine, underwent cycloaddition to 1,3,3-trimethylcylopropene to give 2-oxa-3-azabicyclo[3.1.0]hex-3-enes 2.274,275... 

A2-Isoxazolines are readily available from the 1,3-dipolar cycloaddition of nitrile N-oxides with alkenes and from the condensation reaction of enones with hydroxylamine. Therefore, methods of conversion of A2-isoxazolines into isoxazoles are of particular interest and of synthetic importance. 

However, the thermolysis of diacylfuroxans (429) yielded two types of nitrile Af-oxides. An uncrowded diacylfuroxan such as (429a) rearranged to the a-acyloximino nitrile N-oxide (430) the diacylfuroxan with bulky substituents such as in (429b) gave rise to the half molecule acyl nitrile N-oxide (431). Both types of nitrile IV-oxides (431) and (430) have been trapped with DMAD and hexafluoro-2-butyne to give isoxazoles in good yield. These reactions are shown in Scheme 97. 

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