Subscribe to RSS
DOI: 10.1055/s-2001-14572
Synthesis of 2-Alkylpyrazole-1-oxides: A Facile Access to 1-Alkyl-5-halopyrazoles
Publication History
Publication Date:
30 September 2004 (online)
Abstract
Selective N-alkylation of 1-hydroxypyrazole 1 into the corresponding 2-alkyl-pyrazole-1-oxides 2a-f has been achieved by treatment with alkyl bromides in the absence of base. Subsequent deoxygenation/halogenation into 1-alkyl-5-halopyrazoles 3a-d and 4a-d using phosphorus oxyhalides is described.
Key words
pyrazoles - alkylations - halogenation - deoxygenation - N-oxides
- 1
Begtrup M.Larsen P.Vedsø P. Acta Chem. Scand. 1992, 46: 972 - 2
Parnell EW. Tetrahedron Lett. 1970, 3941 - 3
Begtrup M.Vedsø P. Acta Chem. Scand. 1996, 50: 549 - 5
Begtrup M. J. Chem. Educ. 1987, 74: 974 ; The reaction with 4-methoxybenzyl bromide was performed in a standard flask under N2 at a positive pressure of 0.4 bar - 6
Rodríguez-Franco MI.Dorronsoro I.Hernández-Higueras AI.Antequera G. Tetrahedron Lett. 2001, 42: 863 ; and references cited therein - 7 5-Iodo-1-methylpyrazole has been prepared in 67% yield using C-5 lithiation of 1-methylpyrazole (hampered by competitive deprotonation at the N-methyl group) followed by reaction with I2, see:
Effenberger F.Krebs A. J. Org. Chem. 1984, 49: 4687 - 9
Ferguson IJ.Schofield K.Barnett JW.Grimmet MR. J. Chem. Soc., Perkin Trans. 1 1977, 672 - 11
Hung DT.Nerenberg JB.Schreiber SL. J. Am. Chem. Soc. 1996, 118: 11054 - 12
Begtrup M. Acta Chem. Scand. 1973, 27: 2051
References
Note that the numbering in the pyrazole ring changes upon reduction.
8We previously described the preparation of 5-chloro- and 5-bromo-1-benzylpyrazole via selective chlorination/bromination of 2-benzylpyrazole-1-oxide and subsequent deoxygenation using POCl3, for details see ref. 1.
105-Chloro-1-methylpyrazole and 5-chloro-1-benzylpyrazole have been prepared by treatment of the corresponding
5-hydroxy-1-alkylpyrazoles with POCl3 at 155 °C, for details see ref. 12.