Isoxazole, 5- 3,5-diphenyl

Isoxazole, 3,5-dimethyl-4-(p-nitrophenyl)-bromination, 6, 51 Isoxazole, 3,5-dimethyl-4-vinyl-oxidation, 6, 27, 54 Isoxazole, diphenyl-mass spectra, 6, 6-7 Isoxazole, 3,4-diphenyl-... 

Phototransformation of pyridazine 1,2-dioxides sharply contrasts with that of pyridazine 1-oxides. Pyridazine 1,2-dioxide derivatives give 3a,6a-dihydroisoxazolo[5,4- f]isoxazoles (53) through postulated bisiminoxyl radicals. 3,6-Diphenylpyridazine 1,2-dioxide gives, besides the corresponding bicyclic derivative (53), 3-phenylisoxazole (54) and 4,5-diphenyl-furoxan (55). The last two products can be explained by generation of the nitrile oxide from the intermediate (53) with subsequent dimerization to the furoxan (55 Scheme 18) (79T1267). 

Isoxazoles largely undergo photochemical isomerization to azirines, which sometimes undergo a further thermal or photochemical reaction. 3,4,5-Triarylisoxazole (529) formed the 2,3-diphenyl-3-benzoylazirine (530) which underwent further reaction to the oxazole (531) 72JA1199). A small amount of the corresponding benzoyl ketenimine was also obtained. 

In theory, three isoxazolines are capable of existence 2-isoxazoline (2), 3-isoxazoline and 4-isoxazoline. The position of the double bond may also be designated by the use of the prefix A with an appropriate numerical superscript. Of these only the 2-isoxazolines have been investigated in any detail. The preparation of the first isoxazoline, 3,5-diphenyl-2-isoxazoline, from the reaction of )3-chloro-)3-phenylpropiophenone with hydroxylamine was reported in 1895 (1895CB957). Two major syntheses of 2-isoxazolines are the cycloaddition of nitrile A-oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamine. Since 2-isoxazolines are readily oxidized to isoxazoles and possess some of the unique properties of isoxazoles, they also serve as key intermediates for the synthesis of other heterocycles and natural products. 

The treatment of 4-benzoyl-3-phenylisoxazolin-5-one with KOH generated 3,5-diphenyl-isoxazole-3-carboxylic acid via a ring-opened intermediate as shown in Scheme 69 (61CB1956). 

Disubstituted and trisubstituted 3-isonitrosopyrroles rearrange to 3-acylisoxazoles under the influence of hot, dilute mineral acids. For example, isonitrosotriphenylpyrrole (436), when treated with boiling alcoholic mineral acid, is converted into 3-benzoyl-4,5-diphenyl-isoxazole (437) (62HC(17)1, p. 34). 

The treatment of 3-acylisoxazoles (438) with hydroxylamine hydrochloride gives furazan ketones (439). On the other hand, furazan ketones (439) rearrange to 3-acylisoxazoles (438) with a loss of hydroxylamine under the influence of a mineral acid. Thus, by refluxing phenacylphenylfurazan with concentrated alcoholic hydrogen chloride, 3-benzoyl-5-phenyl-isoxazole is formed similarly, phenyl(phenacylphenyl)furazan gives 3-benzoyl-3,5-diphenyl-isoxazole (62HC(17)1, p. 35). 

Furazano[3,4-/]quinoxaline, 7,8-diphenyl-synthesis, 6, 412 Furazanothiophene synthesis, 6, 417 Furazans, 6, 393-426 biological activity, 6, 425 bond angles, 6, 396 bond lengths, 6, 396 coordination compounds, 6, 403 diamagnetic susceptibilities, 6, 395 dipole moments, 6, 395, 400 heats of combustion, 6, 400 heterocyclic ring reactions, 6, 400-403 IR spectra, 6, 398 isoxazoles from, 6, 81 mass spectra, 6, 399 microwave spectroscopy, 6, 395, 396 MO calculations, 6, 395 monosubstituted... 

Isocyanide, benzyl, 55, 98 Isocyanide, butyl-, 55, 98 Isocyanide, cyclohexyl-, 55, 98 ISOCYANIDE, 1,1-dimethylethyl- [Isocy-amde, tert-butyl-], 55,96 Isocyanide, dodecanyl- 55,98 Isocyanide, ethyl- 55,98 Isocyanide, methyl-, 55, 98 Isocyanide, phenyl-, 55, 98 1//Isoindole 1,3(2//) dione, 2 amino [Phthahmidc, N-amino-], 55, 115 1//-ISOINDOLE-1,3(2//)-DIONE, trans-( )-2-(2,3-diphenyl-l-aziridinvl)-[Azindine, frans-2,3-diphenyl-l-phthalimido-], 55, 115 ISOXAZOLE, 3-(4-chlorophenyl)-5-(4-methoxy phenyl)-, 55, 39 Isoxazole 5-(4-chlorophenyl)-3-(4-meth-oxyphenyl)-, 55, 42... 

The synthesis of isoxazoles by use of azolides is illustrated by the following example of 3,4-diphenyl-5-methylisoxazoles, prepared by conversion of the deoxybenzoin oximes with JV-acetylimidazole with the aid of butyllithium 1381... 

Analogous dienophilic behavior is shown by diphenyl cyclopropenone towards oxazoles235 (isoxazoles behave quite different, see p. 78) giving rise to 3-ethoxy-2,6-diphenyl pyrone-4 (366), which may result from a primary Diels-Alder adduct 365 stabilized by elimination of nitrile ... 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

I.4.I.4. Synthetic Biologically Active Compounds Silyl- and carbonyl-substituted isoxazoles have been prepared and screened for their cytotoxic activity (497). Some exhibited moderate cytotoxicity toward the HT-1080 and MG-22A cell lines. The highest activity level has been displayed by 3-methyl-5-diphenyl-methylsilylisoxazole. 

Kinetic studies on alkyl- and phenyl-isoxazoles in 85% acetic acid at 150°C have shown that isoxazoles are 100-1000 times more reactive than benzene. The relative 4-bromination rates for 5-phenyl- 3,4-diphenyl- ... 

The tetrahydro-derivatives of the oxazole and isoxazole system are unstable. As a consequence, only acyclic products have been reported from the reductions with complex metal hydrides. 2,5-Diphenyl-oxazole (119) gave 2-benzylamino-l-phenylethanol (120),141 and 3,5-diphenyl-2-isoxazoline (121) was converted to 3-amino-l,3-diphenylpropanol (122)142 on reduction with lithium aluminum hydride. 3-Phenylbenzisoxazole was resistant to reduction with lithium aluminum hydride and sodium borohydride,143 but benz-oxazole (123), benzoxazol-2-one (124), and benzoxazol-2-thione (125) have been reported 141 to yield 2-methylaminophenol (126) on reduction with lithium aluminum hydride. 

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