731 benzonitrile oxide

Dihydrofuran (376) and 2,5-dihydrofuran (377) react with nitrile oxides to give furo[2,3-6 ]isoxazoles (378) and furo[3,4-rf]isoxazoles (379), respectively, as cycloadducts. The double bonds of furan, pyrrole and thiophene also react when the nitrile oxide is generated in situ. Thus furan and benzonitrile oxide gave (380), and with 2-methyl-2-oxazoline the cycloadduct (381) was obtained (71AG(E)810). These and related cycloadditions are discussed in Chapter 4.36. 

The addition of benzonitrile oxide to acrylic acid gave only the 4-carboxylic acid (441) (59MI41601), while addition to cis- and trans-cinnamic esters gave cis and trans diastereomeric pairs of 4-carboxylic acids (442) (Scheme 100) (59MI41600). Arbisono repeated the experiment and, when methyl c/s-cinnamate was used, in addition to the 4-carboxylic acid some 5-carboxylic acid (442) was isolated (66MI41600). The reaction of vinyl bromides with benzonitrile oxide yielded only an isoxazole and not a bromoisoxazoline (Scheme 101) (78JCR(S)192). 

When compound (443), which contains alkene and alkyne moieties, was reacted with benzonitrile oxide, both an isoxazoline (444) and isoxazole (445) were produced, with the former predominating. Oxidation of (444) with permanganate produced 3-phenyl-2-isoxazoline-5-carboxylic acid (446) (67ZOR82i). The reaction of 1-trimethylsilylbut-l-yne-3-ene produced only a compound which reacted at the alkenic unit. Oxidation of the adduct also produced (446) (68ZOB1820). These reactions are shown in Scheme 102. 

The reaction of benzonitrile oxide with (447) or (448) produced only (449). No isoxazoline (450) was observed in the reaction with (447) (80MI41601). 

The cycloaddition of benzonitrile oxide to cis- and rrans-l,2-dichloroethylene produced the appropriate cis- and trans-4,5-dichloro-3-phenyl-2-isoxazoline diastereomers. Base elimination produced only one compound, 4-chloro-3-phenyloxazole (Scheme 103) (70CJC3753). 

The addition of benzonitrile oxide to cyclooctatetraene produced a monoadduct which was induced to undergo valence tautomerism to produce a tricycloisoxazoline (Scheme 104). A similar reaction with tropone gave a minimum of eight adducts from which two monoadducts were isolated (Scheme 104) (70T5113). 

The reaction of benzonitrile oxide with the bicyclic isoxazoline (451) produced the three fused diisoxazoles shown in Scheme 105 (77JCS(Pi)2222). 

The reaction of arylnitrile oxides with 1,1-diphenylallenes gave a mixture of 4-methylene-2-isoxazolines (Scheme 106) with major attack at the C(2)—C(3) double bond (74JCS(P2)l30l, 76CSC67, 76CSC71, 72JCS(P2)1914) and not a mixture of the 4- and 5-methylene compounds. 1-Phenoxyallene and benzonitrile oxide produced a mixture of positional isomers and a spiro compound (Scheme 107) (79JOC2796). 

The reaction of benzonitrile oxide with dimethylsulfonium methylylide or triphenylar-sonium methylylide produced 3-phenyl-2isoxazoline (Scheme 116) (67MI4I602, 68G48). A similar reaction of benzonitrile oxide with diazomethane likewise gave 3-phenyl-2-isoxazo-line via intermediate (470) (Scheme 117). 

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

Alkynic esters react with nitrile oxides in a pH dependent reaction to product isoxazolin-5-ones (Scheme 145) (71JCS(C)86). Alkynic ethers also react with benzonitrile oxide to produce an isoxazole-ether which on treatment with HCl or HBr gave an isoxazolinone (Scheme 145) (63CB1088,58MI41600). The reaction of benzonitrile oxide with dimethoxyketene yielded a dimethyl acetal which was split with acid into the isoxazolinone (Scheme 145) (59G15H). 

Benzonitrile oxide reacted with 3-phenyl-4-benzylideneisoxazolinone to produce two isomeric spiro compounds (Scheme 153) (72MI41609,72MI41608). The reaction of benzonitrile oxide with ketene produced a spiro derivative (67MI41600) with allenes, bis(spiroisoxazo-lines) along with monoaddition products were formed (Scheme 154) (79JOC2796, 70CR(C)-(271)1468). 

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

The 1,3-dipolar eyeloaddition of nitrile oxides to 2(5//)-furanones substituted at C5 by sulfur-bearing groups were also studied with respeet to the regio- and ste-reoseleetivity of the reaetion (96T3457). Benzonitrile oxide (R = Ph), for... 

The 2,3-benzoxazepin-l(3//)-one 4 (NR2 = pyrrolidin-l-yl), a stable colorless solid, is obtained in low yield in the reaction of benzonitrile oxide with 3-(pyrrolidin-l-yl)-l//-2-benzopyran-l-one (3).5... 

Dipolar cycloaddition of benzonitrile oxide to 5-methoxy-6-methyl-6FM,4-diazepine results in a l,2,4-oxadiazolo[4,5-d][l,4]diazepine.189... 

An interpretation based on frontier molecular orbital theory of the regiochemistry of Diels Alder and 1,3-dipolar cycloaddition reactions of the triazepine 3 is available.343 2,4,6-Trimethyl-benzonitrile oxide, for example, yields initially the adduct 6.344... 

Interestingly, benzonitrile oxide does not react with thiirene dioxide 19b even in boiling benzene, whereas the electron-rich diene l-piperidino-2-methyl-l, 3-pentadiene (177) does react under the same reaction conditions to give the expected six-membered [4 + 2] cycloadduct 178, accompanied by sulfur dioxide extrusion and 1,3-hydrogen shift to form the conjugated system 179175 (equation 70). 

Aspects of benzonitrile oxide cycloaddition to all three parent diazines have been investigated <96T6421>, and the stereochemistry of resultant biscycloadducts determined <96JCR(S)220>. 

In the reaction of benzonitrile oxide (1,3-dipolar addition) with AyV -thiocarbonyldi-1,2,4-triazole the cyclic addition product has been isolated in 87% yield -170- ... 

The stannanimine [(Me3Si)2N] 2Sn=NDip(Dip = 2,6-diisopropylphe-nyl), undergoes a [2 + 3] cycloaddition with benzonitrile oxide depicted below,103 with 2,6-diethylphenyl azide, a stannatetrazole is formed.88... 

Corsaro and co-workers studied the reaction of pyridazine, pyrimidine, and pyrazine with benzonitrile oxide and utilized H NMR spectral analysis to determine the exact structure of all the cyclized products obtained from these reactions <1996T6421>, the results of which are outlined in Table 1. The structure of the bis-adduct product 21 of reaction of pyridazine with benzonitrile oxide was determined from the chemical shifts of the 4- and 5-isoxazolinic protons at 3.76 and 4.78 ppm and coupled with the azomethine H at 6.85 ppm and with the 5-oxadiazolinic H at 5.07 ppm, respectively. They determined that the bis-adduct possessed /(-stereochemistry as a result of the large vicinal coupling constant (9.1 Hz). Similarly, the relative stereochemistry of the bis-adducts of the pyrimidine products 22-25 and pyrazine products 26, 27 was determined from the vicinal coupling constants. 

As with other diazines, addition of benzonitrile oxide to pyridazines results in the formation of angular-fused tricyclic products C1995T11855, 1996T6421>. 

Compound 384 derived from the reaction of two molecules of benzonitrile oxide (341) with one of BCP (3). Its formation can be explained with the cycloaddition of a second molecule of 341 to the isoxazoline Ml to give the isoxazolidine M5, which undergoes a thermal rearrangement to 384 (Scheme 54). 

A DFT-HSAB study provides a quantitative rationalization of regioselectivity in 1,3-DC of 4-substituted benzonitrile oxides towards methyl propiolate not amenable to FMO and electron-demand theory <06CEJ1156>. 

Analogously, the mesoionic jV-methyl thiazol-5-ones and l,3-dithiol-4-ones afforded A-methyl-4-pyridones and thiapyran-4-ones when reacting with diphenyl cyclopropenone and its thione261. Benzonitrile oxide apparently gives a 1,3-dipolar cycloaddition to the C=0 group of diphenyl cyclopropenone rationalizing the formation of triphenyl-l,3-oxazin-6-one 41626i ... 

The reaction of the ( -configured Schiff base 315 with benzonitrile oxide gave the 4,5-dihydro-l,2,4-oxadiazole 316 as a single diastereomer (Equation 59) <1999AXC650>. 

High diastereomeric ratios were observed in the 1,3-DC of various nitrile oxides to the chiral acryloylhydrazide 38. For example benzonitrile oxide afforded the isoxazoline 40 in 98% de <00TL1453>. The levels of facial selectivity obtained in the same 1,3-DC with the chiral 3-acryloyl-2-oxazolidinone 39 was very low (dr 43 57), but in the presence of MgBr2 (1 equiv) the reaction proceeded with high diastereoselectivity to give preferentially the isoxazolidine 41 in 92% de <00TL3131>. 

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