Regioselectivity in azoles alkylation. Benzylation of indazole under conditions of the phase-transfer catalysis

Full text of DOI:10.1134/S1070428002120266

ISSN 1070-4280 Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 2, pp. 292-293. Ó Pleiades Publishing, Inc. 2006.
Original Russian Text Ó A.E. Shumeiko, A.A. Afon’kin, N.G. Pazumova, M.L. Kostrikin, 2006, published in Zhurnal Organicheskoi
Khimii, 2006, Vol. 42, no. 2, pp. 309-310.
SHORT
COMMUNICATIONS
Regioselectivity in Azoles Alkylation. Benzylation of Indazole
under Conditions of the Phase-transfer Catalysis
A.E. Shumeiko,A.A.Afon’kin, N.G. Pazumova, and M.L. Kostrikin
Litvinenko Institute of Physical Organic and Coal Chemistry, National Academy of Sciences of Ukraine,
Donetsk, 83114 Ukraine
e-mail: ashum@ukrtop.com
Received August 23, 2005
DOI: 10.1134/S1070428002120266
on one or another of the nitrogen atoms [3]. Two isomers
form at the indazole benzylation.
The alkylation of indazole and other nitrogen-containing
heterocycles under the conditions of the phase-transfer
catalysis may be regarded as a convenient procedure for
preparation of various heterocyclic and other compounds
[1, 2]. In these syntheses a problem exists of isomers
formation depending on the direction of the alkyl attack
The ratio of isomers I and II depends essentially on
the mode of performing reaction under the phase-transfer
conditions. The phas-transfer catalysis was carried out
in systems liquid–solid and liquid–liquid. The data obtained
for indazole benzylation are given in the table. As seen,
the isomer ratio is considerably affected by the reaction
temperature:At lower temperature increased the fraction
of isomer II (cf. runs nos. 1–3). At the same time the
isomer ratio at a constant temperature is sensitive to the
nature of the solvent (cf. runs nos. 3 and 5). The most
significantly the isomer ratio is affected by the nature of
1
1
1
1
,,
Benzylation of indazole under the conditions of the phase-transfer catalysis
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a System liquid–solid.b System liquid–liquid.
294

REGIOSELECTIVITY IN AZOLESALKYLATION.
295
b. In a system liquid–liquid. To a mixture of 3 mmol of
indazole, 3 mmol of benzyl chloride, and 0.015 mmol of
catalyst in 20 ml of solvent was added 20 ml of 50%
water solution of potassium hydroxide. The emulsion was
vigorously stirred with a magnetic stirrer for 6 h at room
temperature, the organic layer was separated, washed
with water till neutral washings, and dried with sodium
sulfate. Further workup was as described above.
The isomer composition was estimated by 1H NMR
spectroscopy. The 1H NMR spectra were registered from
solutions in deuterochloroform on a spectrometer Varian-
300 (operating frequency 300 MHz) using TMS as internal
reference. 1H NMR spectrum, d, ppm., isomer I: 8.03 s
(3H), 7.08–7.32 d (7H); isomer II: 7.81 s (3H), 7.59–
7.64 d (7H).
the catalyst. For instance, at growing hydrophobicity of
the catalyst in going from poly(ethylene glycol) to ammon-
ium salts an inversion of isomer ratio was observed (cf.
runs nos. 6 and 8). The reaction under the phase-transfer
conditions in the system liquid–liquid provided virtually
equal amounts of both isomers when the organic phase
was benzene. Yet at the use of carbon tetrachloride the
replacement of the ammonium salt catalyst by a crown
ether resulted in decrease in the content of isomer I in
the mixture of isomeric N-benzylindazoles (cf. runs nos.
12 and 13). Thus the use of the phase-transfer catalysis
makes it possible to carry out regioselective alkylation of
azoles furnishing the target products in high yield.
General procedure of indazole alkylation. a. In a
system liqiud–solid. A mixture of 3 mmol of indazole,
3 mmol of potassium carbonate, 3 mmol of powdered
potassium hydroxide, 0.015 mmol of catalyst, and 3 mmol
of benzyl chloride in 20 ml of solvent were boiled for 16
h, then the precipitate was filtered off and washed with
hot solvent, and the solution was dried with sodium sulfate.
On removing the solvent the residue was distilled.
REFERENCES
1. Dou, H. and Metzger, J., Bull. Soc. Chim. 1976, p. 1861.
2. Pilarski, B., Lieb. Ann., 1983, p. 1078.
3. Claramunt, R., Elguero, J., and Garceran, R., Heterocycles,
1985, p. 2895.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 2 2006