Isoxazolo- -isoxazoles, preparation

A-phenylmaleimide/ ° The complex nitrile oxide (736), prepared from dichloroglyoxime (HON=CCl—CC1=N0H) and dipropargylamine, forms the intramolecular cyclo-adduct 137) 3,6-Diphenylpyridazine 1,2-dioxide (738) rearranges photochemically to the isoxazolo-isoxazole (739), which is also produced by the oxidation of the dioxime HON=CPhCH=CHCPh=NOH. Regiospecific cycloaddition of benzonitrile oxide to the pyrazoline (740) affords the pyrazolo-oxadiazole (741)/ ... 

Isoxazolo[5,4-, [l,2,4]triazine-4-ones are prepared by six-membered cyclizations of diazonium salts onto adjacent ester or amide substituents on the isoxazole ring (Section 10.13.9.1.2(i)). [l,2,5]Oxadiazolo[3,4- ]pyrazines (Section 10.13.9.1.2(ii)) and [l,2,5]oxadiazolo[3,4- pyridazines (Section 10.13.9.1.2(iii)) are traditionally accessed by reliable six-membered condensation reactions to give the fused pyrazine and pyridazine rings, respectively. 

The isoxazole-to-oxazole rearrangement has been also used in the synthesis of benzocondensed derivatives. The irradiation of benzisoxazoles 81 in water (high-pressure Hg lamp) produces almost quantitative yields of the corresponding ben-zoxazoles 82 (Scheme 12.24) [53]. Benzoxazolin-2-ones 83 are similarly obtained [54], Furthermore, oxazolo[5,4-b]pyridines 84 and oxazolo[5,4-b]quinoline 85 are obtained by preparative-scale photolysis in ether with a high-pressure Hg lamp of the corresponding isoxazolo[5,4-b]pyridines or isoxazolo[5,4-b]quinoline, respectively (Scheme 12.24) [55]. 

Neither of these systems has been prepared in the fully conjugated state. The tetrahydro-isoxazolo[4,3-e][l,2,4]triazine (145) is prepared by cyclization of the benzylidene triazinone (144) with hydroxylamine (Equation (18)) <82iJC(B)ii5>. Manganese dioxide oxidation of the isoxazole (146) forms the isoxazolo[4,5-e]triazine derivative (147) (Equation (19)) <86JHC1795>. 

Azine approach. Acid-catalyzed cyclization of 2-/3 -oxoalkylpyridine 1-oxides (37) constitutes a general method for the preparation of the isoxazolo[2,3-a]pyridinium ring system (77JOC1364). By analogy to the synthesis of isoxazoles from nitrile oxides, the oxo chain should be replaceable by an alkynyl or ethenyl chain, the latter containing a substituent which can readily be eliminated from the cyclic product. 

Amino derivatives of isoxazole, 1,3,4-oxadiazole, thiazole, 1,2,4-thiadiazole and 1,3,4-thiadiazole containing the amino group as part of a partial amidine structure react with trichloromethanesulfenyl chloride to give isolable trichloromethanesulfenamides which react with substituted anilines to yield fused thiadiazoles of general structure shown in equation (9). The method has been used to prepare 3H-isoxazolo[3,2-c]-, 3H-thiadiazolo[2,3-c]-, 3H- l,3,4-thiadiazolo[2,3-c]- and 3//-[l,2,4]thiadiazolo[4,3-d]-[l,2,4]thiadiazoles, as well as 3//-[l,2,4]thiadiazolo[3,4-6][ 1,3,4]oxadiazoles (75JOC2600). 

Beginning in 1946 when it was shown that treatment of acid chlorides of hydroxamic acids with alkali hydroxide gave nitrile oxides (46G148), numerous isoxazole derivatives have been prepared. This method lead to isoxazolo[4,5-d]isoxazoles (equation 31) (59G571). 

The standard procedure including treatment with bromoacetyl bromide and then with hexamethylenetetramine was used to prepare isoxazolo[5,4-e]1.4-diazepin-7-one 59 from 5-amino-4-benzoyl-isoxazole (74HCA1934) (Scheme 25). 

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