3-Methylisoxazole groups

Modification of functional groups incorporated in a heterocycle is possible via ylide reactions. The 5-methylisoxazole (578) on reaction with n-butyllithium and methanesulfenyl... 

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. 

Four main types of glutamate receptor have been identified and cloned. These are the ionotropic receptors (NMDA and alpha-amino-3-hydroxy-5-methylisoxazole, AMP A, and kainate types) and a group of metabotropic receptors of which eight types have been discovered. The AMP A and kainate receptors are involved in fast excitatory transmission whereas the NMDA receptors mediate slower excitatory responses and play a more complex role in mediating synaptic plasticity. 

The effects of an ortho-methyl substituent are summarized in Table 7.1. The majority of the results demonstrates the differences in the bond orders within a given molecule, which causes activation across the 4,5-bond to be greater than that across the 3,4-bond. Curiously the combined effects of two methyl groups are not additive, nor are the discrepancies between observed and calculated reactivities in the same direction di-methylisoxazole is less reactive than predicted (the expected result), whereas the other dimethylazoles and 1,2-dimethylpyrazolium are more reactive than predicted. There are no obvious explanations for these discrepancies other than the fact that large extrapolations of rate data are required in this work. This latter may account for the fact that activation by the ortho-methyl group in I-methylpyrazolium is in the opposite direction expected from the bond-order difference. 

Radical bromination with fV-bromosuccinimide often succeeds. Thus, 2,5-disubstituted 4-methyloxazoles on bromina-tion give the 4-bromomethyl compounds, and methyl groups at the 4- or 5-positions of isoxazoles 568 and 569 can be brominated with NBS. Controlled mono- or dibromination of 3-aryl-5-methylisoxazole-4-carboxylates allows access to aldehydes <2004T2301>. 

E. Condensation Involving Activated Methyl Groups of Methylisoxazoles... 

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