2,4.6-trimethylbenzonitrile oxide

The cycloaddition of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to tricar-bonylchromium complexed styrenes proceeds with high stereoselectivity (Scheme 1.17), thus offering a new synthetic route to optically active 3,5-di-substituted 4,5-dihydroisoxazoles (213). The preferred formation of cycloadducts 44 rather than 45 shows that nitrile oxide attacks the it face opposite to Cr(CO)3 and the reactive rotamer of the dipolarophile is transoid (213). 

Allenes add nitrile oxides either to one or two double bonds. For mono- and 1,1-disubstituted allenes, relative activity of the two bonds depends on the nature of substituents. The reaction (Scheme 1.18) of N-propadienylanilines 54 with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide proceeds site- and regioselectively to give 5-substituted 4-methylene-4,5-dihydroisoxazoles 55, which add a second molecule of nitrile oxide to afford 4,5/-spirobi-(4,5-dihydroisoxazoles) 56. Dihy-droisoxazoles 55 isomerize to 4-(2-aminobenzyl)isoxazoles 57 via a Claisen-type rearrangement (224). 

Reactions of arylsulfonylallenes with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide (227) proceed in a manner similar to that of the above-mentioned sulfides. Probably, both 4- and 5-alkylidene-4,5-dihydroisoxazole cycloadducts are initially formed which then undergo different transformations. 4-Alkylidene isomers give spiro adducts such as 60 with an additional molecule of nitrile oxide, while 5-isomers convert to isoxazoles 61, products of their prototropic rearrangement. 

Coumarin reacts with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide affording a single regioisomer 101 (R = 3,5-020, Me ) in high yield (269). 

Stable 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide reacts with 2- and 4-aminopyridines in their imino forms, if acids are present to promote the formation of imine, to give cycloadducts such as 168 (337). 

The kinetic data for cycloadditions of 2,4,6-trimethylbenzonitrile oxide to benzonitriles are consistent with a concerted although asynchronous reaction with a transition state, in which the formation of the O—C bond is more advanced than the making of the C—N bond <90JCS(P2)245>. 

Thermal addition (105°-142°) of DMAD to other N-substituted pyrroles (19a-d)80 83 gave azabicycloheptadienes (20) in yields of 30-45% lower temperatures sufficed for 19e-h. The reversibility of the addition was demonstrated for 20f, 60% of which after 9 hours at 65° in carbon tetrachloride was converted back into 19f compound 20h, however, was unaffected. The azabicycloheptadiene 20 (R = C02Et) undergoes cycloaddition with 1 mole of 2,4,6-trimethylbenzonitrile oxide at both double bonds to give 26 and 27, and both these products... 

The chiral induction of carbohydrate enol ethers in 1,3-DC with some aromatic nitrile oxides was investigated. The highest diastereoseletivity (28 1 dr) was achieved with a 3-0-vinyl-p-D-fructopyranose derivative and 2,4,6-trimethylbenzonitrile oxide <02TA2535>. 

This concept can also be applied for the synthesis of 3-perfluoroalkyl-and 3,4-bis(perfluoroalkyl)-substituted pyrroles [82JOC4779 91JFC(53)-285]. The Diels-Alder adduct from A-(tert-butoxycarbonyl)pyrrole and perfluoro-2-butyne exhibits remarkable thermal stability, but after a second [4 + 2] addition of 2,4,6-trimethylbenzonitrile oxide the newly formed adduct is capable of a retro-Diels-Alder reaction, giving 3,4-bis(trifluoro-methyDpyrroles (82S313). 

Heating of several heterocyclic ring compounds gives rise to the formation of carbodiimides. For example, 3-methyl-2-phenyl-l-azirine 140 on treatment with 2,4,6-trimethylbenzonitrile oxide affords the carbodiimide 141, mp 39 1... 

Benzocyclopropene reacted with benzonitrile oxide to give a Diels-Alder adduct 2a with norcaradiene structure in 10% yield together with a mixture of stereoiso- and regioisomeric bis-adducts using 2,4,6-trimethylbenzonitrile oxide the yield of monoadduct 2b increased to 27%. The bis-adducts are derived from reaction of the nitrile oxide with the diene moiety of the monoadducts. 

Diaryl-l,3,4-oxadiazin-6-ones (147) undergo a stepwise 1,3-dipolar cycloaddition with 2,4,6-trimethylbenzonitrile oxide to yield the bis-adducts (148) together with varying amounts of the hydrolysis products (149) (Scheme 20) <90JHC1425>. The adducts, whose structures are confirmed by x-ray analysis, arise by sequential addition of the nitrile oxide at the N4—C5 imine bond and the carbonyl group. 

Polymethyl 3a,4,7,7a-tetrahydroindoxazenes (77) are obtained by thermal rearrangement of the benzonitrile oxide-hexamethyl-Dewar-benzene cycloadducts (76).90 Reaction of 2,4,6-trimethylbenzonitrile oxide with 3,6-dimethyl-p-benzoquinone yields the 4,7-dioxo-3a,4,7,7a-tetrahydroin-doxazene78(Ar = 2,4,6-Me3C6H2) or its regioisomer, and addition proceeds similarly with 2,6-dimethyl-p-benzoquinone. In a number of other examples, nitrile oxides were found to cycloadd to the C=0 bond of quinones.91... 

The compounds (33) and (72), where Ar is 3,5-dichloro-2,4,6-trimethylphenyl, were also prepared <77JCS(P2)706>. Thus boiling a solution of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide in thiophen... 

The spiroisoxazoline 18, obtained from the nitrone 17 and dicyanoacetylene, rearranges to the pyiTolidinone 19 below 0 °C <97LA1691>. Irradiation of solvent-free mixtures of polycyclic aromatic hydrocarbons (anthracene, phenanthrene and pyrene) and the nitrile oxides mesitonitrile oxide or 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide in a microwave oven at 650 W for 3.5-10 min. yields isoxazolines, e.t . 20, from phenanthrene <97H(45)1567>. 

Full details of the reaction of hexahuoro-Dewar-benzene with the 1,3-dipoles, phenyl azide and diazomethane (see Vol. 1, p. 268) are available, and further examples of reactions with 2,2,2-trifluorodiazoethane, 2,4,6-trimethylbenzonitrile oxide, and benzonitrile JV-phenylimide have been described. 2-Methoxypenta-fluorobicyclo[2,2,0]hexa-2,5-diene yields an adduct with phenyl azide by addition to the CF=<1F bond, and cji o-5,6-dibromohexafluorobicyclo[2,2,0]hex-2-ene, but not the corresponding tra/u-dibromo-compound, yields adduct (125). 

A soln. of chlorocarbonyl isocyanate in chloroform added dropwise with stirring over 20 min to a soln. of 2,4,6-trimethylbenzonitrile oxide in the same solvent at 0-5, and stirred at this temp, for 2 h then at room temp, for 10 h - 4-chlorocarbonyl-3-(2,4,6-trimethylphenyl)-5-oxo-4,5-dihydro-l,2,4-oxadiazole. Y 75%. F.e.s. K.R. Rao et al.. Synthesis 1988, 994-5. 

Aldimines and ketimines react with benzonitrile oxide to give A -oxadia-zolines (111) in good yields, and 2,4,6-trimethylbenzonitrile oxide combines with phenyl isocyanate to give a 1,2,4-oxadiazolin-5-one (112). 2 Nitrile oxides are also used in the preparation of 1,3,4-dioxazoles (113) from carbonyl... 

The strained allene 316, generated in situ at —78 °C, reacts with 2,4,6-trimethylbenzonitrile oxide across the C=P bond to give the cycloadduct 317 in 72 % yield... 

Also the reaction of a,a-dichloroisocyanate 847 with anilines was studied by Samarai and Vovk in presence of equimolar amounts of 2,4,6-trimethylbenzonitrile oxide [546]. The role of nitrile oxide consists in its unique blocking of the initial stage of the reaction to form 904 [547]. Nitrile oxide can be recovered in almost quantitative yield after completion of the process. It was estabhshed by IR spectroscopy that the reaction actually proceeds through isocyanates 901, which undergo intramolecular cyclization (Scheme 186). 

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