Other C-linked substituents

In theory two carbanions, (189) and (190), can be formed by deprotonation of 3,5-dimethylisoxazole with a strong base. On the basis of MINDO/2 calculations for these two carbanions, the heat of formation of (189) is calculated to be about 33 kJ moF smaller than that of (190), and the carbanion (189) is thermodynamically more stable than the carbanion (190). The calculation is supported by the deuterium exchange reaction of 3,5-dimethylisoxazole with sodium methoxide in deuterated methanol. The rate of deuterium exchange of the 5-methyl protons is about 280 times faster than that of the 3-methyl protons (AAF = 13.0 kJ moF at room temperature) and its activation energy is about 121 kJ moF These results indicate that the methyl groups of 3,5-dimethylisoxazole are much less reactive than the methyl group of 2-methylpyridine and 2-methylquinoline, whose activation energies under the same reaction conditions were reported to be 105 and 88 kJ moF respectively (79H(12)1343). 

The 2-alkyl group of 2-alkylisoxazolium salts is also susceptible to a -deprotonation. For example, treatment of 3,5-distyrylisoxazolium salt (199) with potassium methoxide followed by acid hydrolysis gave the natural /3-diketone curcumine (77H(7)24l). 

With l,3-dimethyl-2,l-benzisoxazolium salts, however, considerable reactivity has been reported. Condensation occurs readily with aldehydes, ketones, orthoesters and diazonium salts to yield styryl, cyanine and azo compounds, respectively (78JOC1233). In the presence of triethylamine, dimerization was observed, and the reactions of the cation were considered to involve the intermediacy of the anhydro base (77JOC3929). 

3-Methyl-2,l-benzisoxazole and its 6-methoxy derivative are both readily brominated at the 3-methyl group with NBS (79TL4687, 74RTC139). The 4-methoxy isomer gives only the 7-bromo compound unless excess of the reagent is used, when 7-bromo-3-(bromomethyl)-2,l-benzisoxazole is obtained in 52% yield (74RTC139). However, there is 

The condensation of 5-phenyl-3-(p-tolyl)isoxazole (210) with benzylidineaniline gave the stilbene derivative (211) (78AHC(23)l7l). 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxyIic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyI-5-methylisoxazoIe (215) 73OS(53)70). 

Derivatives of this type formed from 4-dimethylaminopyridine possess considerably more stability and can be isolated readily. 

The typical reaction is Michael addition of nucleophiles thus, 1-vinylpyridinium ion (967) adds A-, S- and C-nucleophiles to give products of type (968). A-Vinyl groups can also undergo polymerization. 

A-Allyl compounds can be rearranged to A-propenyl derivatives. Similarly, A-propargyl compounds (969) give A-allenyl derivatives (970). 

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Other C-Linked Substituents 4.07.3.2.1 Saturated alkyl groups... 

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