Isoxazoles quaternary salts

King and Durst have recently found the ring opening of trisubsti-tuted isoxazole quaternary salts to result in the formation of 1,3-(2 )-oxazine derivatives. ... 

Quatemization of the isoxazole nitrogen atom makes the ring particularly susceptible toward nucleophilic attack there is a certain analogy here with pyridine. The cleavage of the ring proceeds extremely readily in quaternary salts of isoxazole, even occurring by the action of such weak nucleophilic agents as the anions of carboxylic acids. 

The cleavage proceeds under extremely mild conditions in aqueous solution at room temperature and can therefore be used for complicated syntheses. The mechanism of this reaction proved to be very complicated and has been elucidated only recently. The ring opening of quaternary salts of trisubstituted isoxazoles by nucleophiles proceeds under similar conditions, and the mechanism of this reaction was extensively studied by Kohler et The authors... 

The early stages of the reaction of the quaternary salt can be regarded as proceeding in a manner exactly analogous to that by which the isoxazoles themselves are degraded, the j8-oxoketene imine structure (148) being one mesomeric form of a compound which could alternatively be formulated as a nitrilium betaine. However, by contrast with the products from the isoxazoles (i.e., enolates of /3-keto-nitriles), this is electrically neutral and susceptible to further nucleophilic attack. 

Two new syntheses to fused isoxazoles are worth mentioning. In a study for the synthesis of various related fused [l,3,5]triazinium salts, Okide described <1994JHC535> the conversion of 3-amino-5-methylisoxazole 223 with the iminium salt 224. The quaternary perchlorate salt 225 was obtained in medium yield (44%). A Russian research group <2004KGS592> reported that the isoxazole derivative 226 undergoes thermal cyclization when heated in xylene at higher temperature for an extended time, and the cyclized product 227 can be obtained in 53% yield. 

Dicyanoketene ethylene acetal reacts with tertiary amines to give quaternary ammonium inner salts.3 Similarly, it reacts with sulfides to give sulfonium inner salts.3 These products are generally solids that can be used to characterize tertiary amines, and sulfides. Dicyanoketene acetals can be converted to pyrimidines, pyrazoles, or isoxazoles in one step.4... 

Dicyanoketene ethyleneketal reacts with triethylamine in tetrahydrofurune to form the quaternary ammonium inner salt (1) it reacts with dimethyl sulfide to form the sulfonium inner salt (2). The ketal can be converted Into pyrimidines, pyra/oles, or isoxazoles In one step. "... 

---