Synthesis of trifluoromethyl-substituted pyrazoles and 1,2,4-triazines by ring transformation of mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates with phenylhydrazine.
Mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates 1 were easily prepared by the cyclodehydration reaction of N-acyl-N-alkyl-alpha-amino acids with trifluoroacetic anhydride. Due to the presence of the trifluoromethyl ketone and the mesoionic five-membered oxazole, there are three reaction sites to be attacked by the nucleophiles at C-2, C-5 and the trifluoroacetyl group in 1. Based on this model, three modes of regioselective attack by phenylhydrazine were found to provide three different products, i.e., 6-trifluoromethyl-1,2,4-triazines 3, 3-trifluoromethyl-5-pyrazolones 5 and 5-trifluoromethyl-3-hydroxypyrazoles 4, in good yields, respectively, depending on the nature of the solvent and reaction temperature. These three types of different reactions may be explained by the polarity of the reaction solvent and the mesoionic oxazole-ketene tautomerism.
Kawase
Masami
M
Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan. kawase@cc.matsuyama-u.ac.jp
Koiwai
Hiromi
H
D005025:Ethylene Dichlorides; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010080:Oxazoles / Q000737:chemistry*; D010659:Phenylhydrazines / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D013696:Temperature; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology*
D005025:Ethylene Dichlorides; D007202:Indicators and Reagents; D010080:Oxazoles; D010659:Phenylhydrazines; D011720:Pyrazoles; D012997:Solvents; D014227:Triazines; C030299:phenylhydrazine; C024565:ethylene dichloride