Isoxazole carboxylic Acids

Isoxazoles, isoxazolines, isoxazolidines and benzisoxazoles are all thermally stable, distilling without decomposition, but the stability of the system depends on the substitution pattern. For example, aminoisoxazoles distill unchanged but the isoxazole carboxylic acids usually decompose at or above their melting points without giving the corresponding isoxazole. 

Disubstituted and trisubstituted isoxazoles are generally stable to alcoholic and aqueous alkali. Such stability of the ring is characteristic both of alkyl-substituted compounds and of the esters, nitriles, etc., of isoxazole carboxylic acids,for example (127 ->128). 

The mechanism of the decarboxylation of isoxazole-3-car boxy lie acids has not yet been specially studied, but the available experimental evidence allows some suggestions to be made. It seems that on heating isoxazole carboxylic acids in solution, or in the presence of arylhydrazines, it is the acid anion (158) formed which is being de-... 

Another group of reactions with the predominant cleavage of the ring comprises catalytic hydrogenation of isoxazole derivatives and has been investigated only recently. The most commonly used catalyst has been Raney nickel,but use has sometimes been made of platinum catalysts. Hydrogenolysis of the 0—N bond (172—>173) occurs in isoxazole, its homologs,and their functional derivatives, for example, isoxazole carboxylic acids- and 5-aminoisoxazoles. ... 

Some hydroxamic acids of the isoxazole series also display a marked antituberculosis activity. The penicillin derivatives, acylated with isoxazole carboxylic acids possess an antibacterial activity similar to that of penicillin, against resistant species.Among other isoxazole derivatives possessing activity one should especially mention the sulfonamides of this series, and 4-hydroxyiminoisoxazol-5-... 

Sterically hindered derivatives of isoxazole carboxylic acids have yielded a goodly number of antibiotics. Chlorination of the oxime of the appropriately substituted benzaldehydes (15) leads to the intermediates, ( 16. Condensation of the chloro oximes with ethyl acetoacetate in base gives the esters (17) of the desired isoxazole carboxylic acids. Alternately, the esters... 

AMPA (= 2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid)] (isoxazole carboxylic acid)... 

By means of a synthesis of isoxazol derivs with fulminic acid, it was establish that the structure of the acid reported in Ref a is incorrect. It should be 3-isoxazol< carboxylic acid)... 

APA is duly acylated with 3-(o-chlorophenyl)-5-methyl-4-isoxazole carboxylic acid and the resulting cloxacillin base is adequately purified by reerystallization. The base thus obtained is converted to the corresponding sodium salt by treating with an equimolar concentration of NaOH. 

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. 

---