Isoxazoles acetylene derivs

The above reactions provide convenient methods for the preparation of poorly understood acetylene derivatives of pyrazole and isoxazole. 

As shown by the Italian school, the formation of isoxazole derivatives by the action of nitric acid or nitrogen oxides on acetylene derivatives and related reactions proceeds through intermediate nitrile oxides and must, therefore, be included with this type of synthesis. 

The reaction of ethoxycarbonylformohydroximinoyl chloride EtOiCCTNOH with acetylene derivatives gave isoxazoles 206 (R2 = H, C02Et, CC>2Me, C0C6H4N02-4 R3 = C02Et, C02Me, Ph, COPh) (366). 

Isoxazoles from nitrile oxides and acetylene derivatives—Diene syntheses s, 18, 758 isoxazoles from stable sterically hindered nitrile oxides s. G. Grund-mann and J. M. Dean, J. Org. Ghem. 30, 2809 (1965) reactions with cyanogen di-N-oxide s. G. Grundmann et al., A. 687, 191 (1965)... 

Isoxazoles from nitrile oxides and acetylene derivatives. Dicyanoacetylene added to an ethereal soln. of benzonitrile oxide, and refluxed 40 min. 

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

All the isoxazole derivatives formed from acetylene belong to the 3-mono-substituted series (Quilico [12a]). 

The course and orientation of 1,3-cycloadditions will be illustrated by listing examples of actual reactions. Most dipolarophiles have carbon-carbon unsaturated bonds, and give derivatives of 1,2,3-triazole, pyrazole, isoxazole and pyrrole according to the following reactions (unless otherwise indicated, reference is made to monosubstituted dipolarophiles olefins and acetylenes usually, but not always, behave similarly) ... 

Bharate et al. (2013) applied montmorillonite clay Cu(ll)/NaN3 as a heterogeneous catalytic system for the four-component synthesis of isoxazole derivatives in water. The desired 3,5-disubstituted isoxazoles were obtained in moderate to good yields using the domino reactions of aldehydes, hydroxylamine, Af-chlorosuccinimide (NCS), and acetylenes (Scheme 4.61) the catalytic system could be efficiently recycled. 

Methyl-4-nitro-3-isoxazolin-5-one (81) acts as a precursor of nitrile oxide 82. When 81 is reacted with acetylenes and with both electron-rich and electron-deficient alkenes in MeCN/H20 3 1 at room temperature, isoxazole 83 and isoxazohne derivatives 84 are produced regioselectively and in good yield, respectively (Scheme 5.22). In sole MeCN, the isoxazolinone 81 was recovered unchanged even under reflux. 

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