Ketoximes cyclization

Although 1,2-benzisothiazoles can be prepared by the oxidation method, they are also available by cyclization of o-mercaptobenzaldoximes and ketoximes with polyphosphoric acid (72AHC 14)43, 73JCS(P1)356, 77JCS(P2)1114). This method has been improved by the use of S-t- butyl analogues, which do not suffer from the instability of the free thiols (79SST 5)345). 

The lOOC reactions were extended to cyclization of ketoxime 234 which provided the isoxazolidine 235 stereospecifically in 75% yield (Eq. 25). 

Phenyl- and 2-(2-thienyl)-3,3-dimethyl-3//-pyrroles (58) were obtained by the reaction of the corresponding ketoximes 56 with acetylene catalyzed by MOH (M = Na, K) in DMSO. The reaction intermediate observed is the corresponding O-vinyl oxime 57 which undergoes [3,3] sigmatropic rearrangement and cyclization to products 58 (equation 24). The yield of the products obtained strongly depends on the structure of the ketoxime . 

Hydrogenated isoxazole derivatives were obtained by single electron transfer (SET) cyclization of /9,y-unsaturated oximes , by thermal [4- -2] cycloaddition of aldox-imes or ketoximes to conventional dienophiles or isomerization/cyclization of an ortho halogeno or nitro-substituted amidoximes. Preparation of 1,4-disubstituted 3-hydroximino-2-nitro-l-butenes and their oxidative cyclization to 4-nitroisoxazoles are reported " . Synthesis of fluorine-containing substituted isoxazolidines as well as isoxazoles by ultrasonic methods has been also described. 

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

Since oximes are more stable to oxidation and often more available than the corresponding carbonyl compounds they also can be used as starting material for the cyclizations. For instance, quinoxaline-2-aldehyde oxime 49a as well as ketoxime 49b are converted by hydrazine in acidic medium into flavazoles 50 (Scheme 14) (01JHC829). Hydroxylamine, which is liberated in the first step, may act as a hydride ion acceptor. This minimizes using a large excess of arylhydrazine or any another oxidant. 

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

Quinoxaline-3-ketoximes in the presence of pyridine can be cyclized the reaction proceeds by addition of the oxime hydroxy group to the electron-deficient diazine to form a cyclic dihydro derivative which expels the ring function substituent to regain aromaticity, e.g. (45) (66HCA2426). 

The Beckmann rearrangement of ketoximes to the corresponding amides (31), the Fischer indole cyclization, isomerization of epoxides to the corresponding aldehydes, ketones, or alcohols, hydration and ammo-nolysis of epoxides, oxygen-sulfur interchange, formation of diaryl-ureas and -thioureas from condensation of aniline and carbonyl sulfide, and olefin carbonylation occur over zeolite catalysts (62). The oxo reaction over rhodium and cobalt containing zeolites recently has been claimed (22). 

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