Abstract
A simple and efficient method for the synthesis of 2-aryl-4-bromomethyl-5-methyl-1,3-oxazoles 2 and 2-aryl-4-chloromethyl-5-methyl-1,3-oxazoles 3 is described. The reaction of 2-aryl-4,5-dimethyl-1,3-oxazoles 1 with N -bromosuccinimide and N -chlorosuccinimide in acetonitrile under mild conditions provides 4-halomethyl isomers with exceptionally high regioselectivity in moderate to good yields.
Key words
oxazoles - halogenation - regioselectivity - heterocycles - drugs
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12a The structures of 2 and 3 were confirmed by synthesizing the 2-aryl-5-halomethyl-4-methyloxazoles (the regioiso-mers of 2 and 3 ) according to a known procedure (Scheme
[4 1 H/13 C NMR spectroscopy and HPLC analysis. Compounds 2 or 3 and their regioisomers are distinguishable clearly by chemical shifts on 1 H/13 C NMR and retention time on a HPLC analysis.
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13 The regioselectivity was determined by HPLC analysis (HPLC conditions; YMC Pack-SIL A-002 column with 40:1-10:1 n -hexane-THF as the mobile phase). To investigate regioselectivity, we used HPLC with the normal phase, while the 5-halomethyl-4-methyl regioisomers easily decomposed during a HPLC analysis with the reverse phase.
14 One referee kindly suggested other plausible mechanisms (Schemes
[5 6
