Oximino nitriles

Cekovic has examined the addition of electron-deficient olefins to 3-hydroxy radicals [164]. Addition to acrylonitrile of the carbon-centered radicals resulting from the Barton photolysis of alkyl nitrite 173 and subsequent 1,5-hydrogen transfer, yielded a-oximino nitrile 174 (63%, Scheme 57) [165]. 

Rearrangement-cyclization. 6-Oximino nitriles form 2-acetamidopyridines. n treatment with AC2O-ACCI under reflux. The reaction proceeds from rearrangement of iV-acetoxyenamines to C-acetoxy imines, which undergo elimination and csclization. 

The above methodology has been extremely useful for the synthesis of a variety of INOC precursors. For instance, treatment of 0-trimethylsilyl a-bro-moaldoximes 52b, e, f with F ion in presence of unsaturated alcohols 57 produces oximino ethers 58 which can be readily oxidized using NaOCl (Scheme 8) [29]. The transient nitrile oxide intermediates formed undergo spontaneous cyclization to fused isoxazolines 59. The preferred stereoisomer in the formation of the five-membered ring ethers is trans whereas in the six-membered ring ethers the cis isomer predominates (see Table 5). MM2 calculations helped rationalize the experimentally observed stereoselectivites (see Table 5). 

Selective reduction of the nitrile group in 87% yield without the reduction of the carbonyl was achieved by stannous chloride [1153]. Oximes of keto nitriles are reduced preferentially at the oximino group by catalytic hydrogenation in acetic anhydride over 5% platinum on carbon (yield 85%)... 

Construction of pyrazine rings from a-amino nitriles has been sometimes completed through multistep reactions. For example, 2-aminopyrazine 1-oxide 163 is synthesized via amide intermediate 162 formed by reaction of methyl a-aminocyanoacetate with a-oximino carboxylic acid (Scheme 45) <1994H(38)1581>. 

Pyrazine A -oxides have been conveniently synthesized by oxidation of pyrazines (Section 8.03.5.2), and by condensation of a-amino nitriles with a-oximino ketones (Section 8.03.9.3). 

The effect of varying the concentration of the 3-oximino-2-butanone methacrylate moiety was studied next. From the above results, it appears that the optimum nitrile concentration is roughly 15 to 22%. We chose to fix the methacrylonitrile mole fraction at the lower value in order to least perturb the solubility characteristics of the polymer. 

The indirect conversion of an aromatic aldehyde into the corresponding nitrile by dehydration of an oxime is illustrated by the synthesis of veratronitrile (Expt 6.170). The dehydrating agent is acetic anhydride which probably effects an initial acetylation of the oximino group followed by the elimination of acetic acid. 

Nitriles are also formed in excellent yields by the decarboxylation and dehydration of oximino acids with warm acetic anhydride. A good route for obtaining the starting materials consists in the condensation of aldehydes with rhodanine followed by cleavage of the product with alkali and treatment with hydroxylamine. 

A closely related reaction involves the conversion of a-oximino ketones to nitriles by pyrolysis or by the action of thionyl chloride (75%). This reaction constitutes a step in a series for the synthesis of aliphatic acids from valeric to lauric acids. 

Other reactions which form nitrile oxides or their cycloadducts from furoxans are known, but in the majority of these cases their course is not clear. 4-Phenylfuroxan with mild base rearranges to the isomeric a-oximino-phenylacetonitrile oxide (see Section VI). The distillation of 3-ethoxy-carbonylfuroxan-4-carboxylic acid (70) appears to generate the nitrile oxide 72, since one of the products isolated is diethyl furoxandicarboxylate (71).335,336 The diester (71) with anethole is reported to form ethyl 4-anisyI-5-methylisoxazole-3-carboxylate (73),337 but it is not established that the reaction involves the generation of 72 by dissociation of 71, as the authors suggested (see Section V,C,1). See also Section X. 

Oxidative conversion of aldehydes into nitriles. Aliphatic aldehydes are converted directly into nitriles when treated with excess hydroxylamine-O-sulfonic acid at 25° (60-90% yield). Aromatic aldehydes under the same conditions are converted into oximino derivatives, ArCH=NOS03H, which are converted into nitriles either by decomposition at 65 or by cleavage with sodium hydroxide (yields 80-95%). ... 

Nitriles. a-Oximino acids react with phenyl isocyanate in benzene solution at ambient temperatures to form nitriles (equation 1). ... 

N-(l-Oximino-l,2,3,4-tetrahydro-2-naphthyl)hydroxylamine in aq. 5%-NaOH stirred 3 days at room temp, in the presence of air o-(y-nitropropyl)benzo-nitrile. Y 47%. L. B. Volodarsky and V. A. Koptyug, Tetrah. Let. 1964, 2659. 

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