3- -5-methyl isoxazole

METHYL-2-ISOPROPYL-3-PYRAZOLYL DIMETHYLCARBAMATE see DSK200 METHYL ISOSYSTOX see DAP400 METHYLISOTHIOCYANAAT (DUTCH) see ISEOOO METHYL-ISOTHIOCYANAT (GERMAN) see ISEOOO METHYL ISOTHIOCYANATE (DOT) see ISEOOO METHYL ISOVALERATE see ITCOOO METHYLISOVALERATE (DOT) see ITCOOO N -(5-METHYL-3-ISOXAZOLE)SULFANIL, NnDE see SNKOOO... 

Application of this method to heterocyclic acids permits easy preparation of acid chlorides previously requiring special procedures. Thus 5-methyl-3-isoxazole-carbonyl chloride was initially obtained only by the reaction of the sodium salt of the acid with phosphorus pentachloride" or with thionyl chloride the free acid does not react with thionyl chloride alone. An improved procedure is as follows."... 

Eqn. (a) shows the interaction between benzaldehyde and 5-methyl-3-isoxazole carboxylic acid hydrazide in the presence of ethanol at 4°C to 3neld l-benzylidene-2 (5-methyl-3-isoxazolylcarbonyl) hydrazine (I) with the elimination of one mole of water as indicated above. 

Chemicals Required. Benzaldehyde 80 g Ethanol [95% (v/v)] 750 ml 5-Methyl-3-isoxazole-carboxylic acid hydrazide 72 g l-Benzylidene-2-(5-methyl-3-isoxazolylcarbonyl) hydrazine 11.5 g Anhydrous Solvent Ether 500 ml Pure LiAlH 1.85 g Ethyl acetate 25 ml Benzene 20 ml Methanol q.s. 

Methyl-4,5-isoxaxoledione-4-((2-chloropenyl) hydrazone). See Drazoxolon N -(5-Methyl-3-isoxazole) sulfanilamide N -(5-Methyl-3-isoxazolyl) sulfanilamide. See Sulfamethoxazole Methyl jasmonate... 

The importance of this ring-opening reaction is illustrated by the following. 5-Methyl-isoxazole (110) on treatment with ammonia was partly converted into cyanoacetoneimine (111), and when refluxed with phenylhydrazine it yielded the 5-aminopyrazole (113) through the intermediate cyanoacetone (112) (63AHC(2)365). 

The reaction of methyl acetylpyruvate (312) with hydroxylamine hydrochloride gave the 3-carboxylate (313) in 76% yield together with traces of the isomeric 5-carboxylate (314) (78MIP41600). However, the sodium salt (315) of acetylpyruvic acid resulted in 3-methyl-isoxazole-5-carboxylic acid (316) as the major product. 

Fig. 10. Relative energy of the excited states of methyl isoxazole-3-carboxylate and of some reactive intermediates.

Acetonitrile oxide regioseleetively reaets with dialkylaminobutenones to form 5-aeetyl-3-methylisoxazole (322) and a small amount of 4-aeetyl-3-methyl-isoxazole (323) (92SC2902). 

The spectra of isoxazoles have recently been examined in detail. Pino et al. investigated the UV spectra of isoxazole and the methyl-isoxazoles. These spectra revealed characteristic shifts in the maxima depending on the number and position of methyl groups. Such regularities are characteristic only for aromatic systems. The shift is most marked for a C-4 methyl group, and is absent for a C-3 methyl group. 

The nucleophilic substitution reactions are still more limited in scope owing to the instability of the isoxazole ring toward nucleophilic reagents. Homolytic reactions appear to be unknown though some of the reactions being studied are possibly of this type. Besides those reactions which are characteristic of the reactivity of the isoxazole nucleus itself, we shall consider in this section some substitution reactions in the side chain organomagnesium synthesis in the isoxazole series, condensation reactions of the methyl groups of methyl-isoxazoles, and finally some miscellaneous reactions. 

It is only recently that the chloromethylation reaction, well known in the benzene series, has been extended to isoxazoles. It has been thereby found that this reaction results in 4-chloromethyl derivatives (69), their yield decreasing as follows 5-phenyl > 3,5-dimethyl > 5-methyl > 3-methyl isoxazoles > isoxazole. To prove the position of the chloromethyl group these compounds were oxidized to the known isoxazole-4-carboxylic acids (70). It is especially noteworthy that pyridine and its homologs do not undergo chloromethylation. 

Methyl-isoxazole-(3)-carboxylic acid chloride 4-(/3-Aminoethyl)benzene sulfonamide hydrochloride Chloroformic acid methyl ester N-Amlno-hexamethylene imine... 

There is obtained from 4-[)3-[5-methyl-isoxazolyl-(3)-carboxamido]-ethyl]-benzene-sulfonamide (prepared from 5-methyl-isoxazole-(3)-carboxylic acid chloride and 4-()3-aminoethyl)-benzene-sulfonamide hydrochloride, MP 213° to 214°C in pyridine) and chloroformic acid methyl ester, in a yield of 69%, the compound N-[ [-4-[)3-[5-methyl-isoxazolyl-(3)-carbox-amido] -ethyl] ] -benzene-sulfonyl] ] -methyl-urethane in the form of colorless crystals of MP 173°C. 

Carbethoxy-4-hydrOxy-2-methyl-2H-1 -benzothiazine-1,1-dioxide 3-Amino-5-methyl-isoxazole... 

Preparation of S-Acetylsulfanilamido-S-Methy/isoxazole 0.9 gram of 3-amino-5-methyl-isoxazole in 5 cc of pyridine was allowed to react with 2.0 grams of acetylsulfanil chloride accompanied by the generation of heat. After about one hour, water was added to the reaction mixture and the crystal precipitated out was recrystallized from alcohol to give 2.5 grams of 3-acetylsulfanilamido-5-methylisoxazole, melting point (decomposition) 220° to 221°C. 

Ethyl 5-methyl isoxazole-3-carbamate Sulfamethoxazole N-Ethylmorpholine Meclofenamic acid... 

Trifluoroacetonitrile oxide has been used in the synthesis of trifluoro-methyl isoxazoles and isoxazolines (84BCJ2184 86BCJ2631). In the presence of a base it dimerizes to a dioxadiazine (84JOC919). 

Enantiomerically pure 4.5-dihydro-3-[(/J)-(4-methylphenylsulfinyl)methyl]isoxazoles 16 arc readily available from the reaction of metalated 4,5-dihydro-3-methylisoxazoles 14 with (-)-menthyl (5)-4-methylbenzenesulfinate (15), under inversion of the configuration at sulfur, followed by separation of the resulting diastereoiners27-28. 

Dihydro-3- (/ )-(4-methylphenylsulfinyl)methyl isoxazoles 16 General Procedure28 ... 

Both of the 4,5-tran.v-diaslereomers of 4,5-dihydro-4-(4-methoxyphenyl)-5-methyl-3-[(7 )-(4-methylphenylsulfinyl)methyl]isoxazole (24) show excellent stereoselection in reactions with aldehydes. Despite the bulky substituents at the 4,5-dihydroisoxazole nucleus, the stereochemical outcome of the reaction is controlled by the sulfoxide stereogenicity. The pairs of 4,5-dihydro-3-(2-hydroxyalkyl)-4-(4-methoxyphenyl)-5-methylisoxazoles, obtained by desulfurization of the corresponding aldol adducts, have the same configuration at the hydroxy-substituted carbon (C-2 ) and opposite configuration in the 4- and 5-positions of the dihydroisoxazole ring24. 

Seizure maintenance is largely caused by glutamate acting on postsynap-tic N-methyl-D-aspartate and a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/akinate receptors. Sustained depolarization can result in neuronal death. 

This method gives a somewhat tower yield than method 1. Dissolve 14.1 g l-nitro-3-butanone in 30 ml glacial acetic acid and heat to 35° add slowly with stirring to a solution of 5.3 g bromine in 10 ml glacial acetic acid. Evaporate in vacuum, dissolve residue in ether and wash with water, NaHC03 and water. Dry and evaporate in vacuum the ether (can distill 84/2) to get 6 g 1 -nitro-4-Br-3-butanone (1). Add 4.4 g (I) to 25 ml 48% HBr and reflux three hours. Add 50 ml water and steam distill. Neutralize the distillate with K carbonate and extract with ether. Dry and evaporate the extract (can distill 128/20) to get 5.6 g 2-Br-5-Br-methyl-isoxazole... 

Isocarboxazid Isocarboxazid, 2-benzylhydrazid-5-methyl-3-isoxazolecarboxylate (7.2.6), can be synthesized from acetylacetone, which on nitrosation with nitrous acid gives 5-methyl-isoxazol-3-carboxyhc acid (7.2.2). Esterification of this product gives the ethyl ester of 5-methyl-isoxazol-3-carboxyhc acid (7.2.3). The synthesized ester (7.2.3) is further reacted with benzylhydrazine, to give isocarboxazide (7.2.6), or with hydrazine, which forms 5-methyl-isoxazol-3-carboxylic acid hydrazide (7.2.4). Reacting the latter with benzaldehyde gives hydrazone (7.2.5), which is further reduced to the isocarboxazide (7.2.6) [46,47]. 

NMDA, Af-methyl-D-aspartate AMPA, a-amino-3-hydroxy-5-methyl-isoxazole-4-proprionic add 1S,3R-ACPD, L-amino-cydopentane-lS,3R-dicarboxylic add IP3, inosine triphosphate... 

Sulfamethoxazole 4 - Amino -N- 5 -methyl-3 - isoxazolyl)benzene sulfonamide Sulfonylation of aniline, sulfphoamidation with 3-amino-5-methyl-isoxazol... 

ISOXAZOLE 3-SULPHANILAMIDO-5-METHYL-ISOXAZOLE SULPHISOMEZOLE TRIE TRIMETOPRIM-SULFA... 

Stanley, B. G., L. H. Ha, L. C. Spears and M. G. Dee, 2nd (1993). Lateral hypothalamic injections of glutamate, kainic acid, D,L-alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid or N-methyl-D-aspartic acid rapidly elicit intense transient eating in rats. Brain Res 613(1) 88-95. 

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