Nitrile /V-oxides

The cycloaddition of 1-halogeno-l-nitroethene with nitrile /V-oxides leads to the nitro derivatives of isoxazole [520-524], Thus, for example, the reaction of equimolar amounts of 1-chloro- or 1-bromonitroethene with benzonitrile /V-oxidc gave 5-nitro-3-phenylisoxazole [520], The same compound is formed in the reaction of nitrile /V-oxides with ra .s-2-chloro-1 -nitrocthcnc [485], The formation of nitroisoxazoles in these reactions can be explained by the fact that the initial products from the cycloaddition of halogenonitro-A2-isoxazolines more readily eliminate a molecule of hydrogen halide and not HNOr... 

Kubota, T., Yamakawa, M., Takasuka, M. et al. (1967) Molecular complexes of aromatic nitrile V-oxides with iodine, p-naphthof and phenol. 7. Phys. Chem., 71, 3597-3604. 

For Negishi reactions in which the pyridines are nucleophiles, the pyridylzinc reagents are usually prepared from the corresponding halopyridines [6, 20, 21]. An excess of 2-chlorozincpyridine /V-oxide (26), arising from 2-bromopyridine N-oxide hydrochloride (25), was coupled with vinyl triflate 27 in the presence of Pd(Ph3p)4 to furnish adduct 28 [20]. Recently, an efficient Pd-catalyzed cyanation of 2-amino-5-bromo-6-methylpyridine (29) using zinc cyanide has been reported to afford pyridyl nitrile 30 [22]. 

Solvents are rigorously dried by repeated distillation in vacuo from phosphorus-(V) oxide. The alkyl nitriles are generally predried by refluxing them over calcium hydride for several days, then distilling several times from phosphorus (V) oxide, and finally from potassium carbonate the liquid is then stored either over phosphorus (V) oxide on the vacuum line or in contact with molecular sieves in the dry-box. 

During thermolysis diacylfuroxans are transformed into the /V-oxides of a-keto nitriles, which form cyclic adducts in situ with various dipolarophiles [525], This method was used for the production of 4-nitro-3-(2-acetoxybomyl-2-carbonyl) isoxazole (yield 50%) by boiling bis(2-acetoxybomyl-2-carbonyl)furoxan with an excess of trans-/)-dimethylammonitroethene in toluene (Scheme 84). 

The nitrile group of (172) reacts with hydroxylamine to give the hydroxyamidine (173). Reduction of the nitro to an amino group and then treatment with trimethyl orthoformate gives the aminopyrazolopyrimidine (V-oxide (174) which, with care, can be hydrolyzed to the cyclic hydroxamic acid (175 Scheme 54) (70JHC863). 

Nitrile-A -oxides are reducible at rather positive potentials to the nitriles thus 2,4,6-trimethylbenzonitrile-A/ -oxide is reduced at —0.7 V at pH 6 in aqueous ethanol to the corresponding nitrile [254]. 

Mass spectra of a great variety of monocyclic and condensed 1,2,3-triazines have been published. Since all monocyclic 1,2,3-triazines show the same fragmentation pattern, mass spectrometry can be used to determine the structure of isomeric monocyclic 1,2,3-triazines and their V-oxides. In general, the mass spectrum of monocyclic 1,2,3-triazines show peaks for M+, [M+ -N2], for one or two nitriles and one or two acetylenes. This indicates the following fragmentation pattern.1,17,79,8( 89... 

This chapter contains reactions that prepare the oxides of nitrogen, sulfur, and selenium. Included are /V-oxides, nitroso and nitro compounds, nitrile oxides, sulfoxides, selenoxides, and sulfones. Oximes are considered to be amines and appear in those sections. Preparation of sulfonic acid derivatives is described in Chapter 2 and the preparation of sulfonate esters in Chapter 10. 

MJnsaturated acids are rarely formed from -hydroxy acids by means of dehydrating agents, which, instead, afford lactides and anhydrides or, with loss of formic acid, aldehydes. However,, / -unsaturated nitriles can be obtained from a-hydroxy nitriles (cyanohydrins) by means of thionyl chloride45 or phosphorus(v) oxide,46 and are readily hydrolysed to the corresponding <%,/ -unsaturated acids. 

Methylacrylonitrile, CH2==C(CH3)CN 46 Phosphorus(v) oxide (75 g) is weighed rapidly into a flask (500 ml) that is then fitted with a reflux condenser, dropping funnel, and drying tube and warmed in a water-bath at 10-15°. Acetone cyanohydrin (42.5 g) is dropped in with vigorous shaking during 0.5 h, after which the nitrile is removed by distillation from the viscous mass. A second distillation affords a 34.3% (11.5 g) yield of 2-methylacrylonitrile, b.p. 89-91°. 

The chemistry of heterocyclic V-oxides prior to 1970 has been the subject of an extensive review, but most of their reactions with benzyne have been studied more recently. In N-oxides the disposition of bonds at the nitrogen atom can be linear (nitrile oxides), trigonal (nitrones), or tetrahedral (tertiary... 

The reaction has been applied to substituted pyridinecarboxylic acids such as 2-methoxyisonicotinic acid (X-206), or to the parent 2-pyridone. These acid V-oxides form amides and nitriles via the esters. 

When the first HCN adds to butadiene, some undesired branched 2-methyl-3-butenenitrile, 9.29 in Figure 9.6, is formed along with the desired linear 3-butenenitrile. Interestingly, the first HCN addition to butadiene is reversible, because the branched nitrile can be isomerized to the linear form with NiL . This means that 9.29, which is an activated allylic nitrile, can oxidatively add to the nickel to give back the V-allyl nickel cyanide. Labelling studies suggest that this intermediate goes back to HCN and butadiene, before readdition... 

Ketenes also undergo [3+2] cycloaddition reactions with typical 1,3-dipoles, such as nitrones and nitrile oxides. For example, t-butylcyanide V-oxide reacts with diphenylketene... 

Alkylthiazoles can be oxidized to nitriles in the presence of ammonia and a catalyst. For example, 4-cyanothiazole was prepared from 4-methylthiazole by a one-step vapor-phase process (94) involving reaction with a mixture of air, oxygen, and ammonia at 380 to 460°C. The catalyst was M0O3 and V Oj or M0O3, VjOj, and CoO on an alumina support. 

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