Alkylation of phenol with 1-phenyl-3,5-dimethyl-4-chloromethylpyrazole under phase transfer catalysis

Full text of DOI:10.1134/S1070363211080330

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 8, pp. 1747–1748. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.I. Rstakyan, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81, No. 8, pp. 1405–1406.
LETTERS
TO THE EDITOR
Alkylation of Phenol with 1-Phenyl-3,5-dimethyl-4-
chloromethylpyrazole under Phase Transfer Catalysis
V. I. Rstakyan
Institute of Organic Chemistry, National Academy of Sciences of Armenia,
ul. Azatutyan 16, Yerevan, 375091 Armenia
e-mail: vrstakyan@gmail.com
Received March 10, 2011
DOI: 10.1134/S1070363211080330
It is known that heating of 1,3,5-trimethylpyrazol-
4-ylmethanol in the presence of benzyl and hexyl
alcohols affords mainly the mixed ethers of trimethyl-
pyrazolylcarbinol [1]. A similar reaction of trimethyl-
pyrazolylcarbinol with phenol does not yield the pyra-
zolylmethyl phenyl ether, but the products of phenol
C-alkylation in the ortho- and para-positions [2].
At the phenol alkylation the formation of ambident
ions is not excluded [4]. In this case both O- and C-
alkyl derivatives can be formed. Thus, at the alkylation
of phenol I with 1-phenyl-3,5-dimethyl-4-chloro-
methylpyrazole II we isolated and characterized the O-
(V) and C-alkylated products (III, IV) (1:1) in a
total yield of 63%. According to the 1H NMR data, the
C-alkylated products (III, IV) are a mixture of ortho-
and para-isomers in a ratio of 9:1. The proton signal of
the hydroxy group of the isomer III appears downfield
(8.99 ppm) in comparison with the corresponding
signal of the isomer IV (8.21 ppm). Isomer III was
isolated in pure form by crystallization.
In order to determine whether C-alkylated phenol is
a precursor of pyrazolylmethyl ether [3], in the present
work we report the results of phenol I alkylation with
1-phenyl-3,5-dimethyl-4-chloromethylpyrazole II under
phase transfer catalysis.
OH
HO
Me
Me
N
N
+
Me
Me
N
N
Cl
Me
Me
OH
N
phase transfer catalysis
N
IV
III
+
O
Me
II
I
N
Me
N
V
1747

1748
RSTAKYAN
Further investigation showed that the O-alkylated
tallization from a water–ethanol mixture (1:4) yields
pure isomer III, 8.2 g, mp 220°C. H NMR spectrum
1
phenol V is not subjected to any changes under heating
to 200°C (it is not transformed into a C-alkylated
product). Based on these data, one can conclude that
non-catalytic alkylation of phenol with 1,3,5-
trimethylpyrazol-4-ylmethanol leads exclusively to C-
alkylated products [2].
(DMSO-d6), δ, ppm (J, Hz): 2.12 s (3Н, СН3), 2.26 s
(3H, CH3), 3.64 s (2Н, СН2), 6.61 d.d.d (1H, J1 7.6, J2
4, J3 1.1), 6.76 d. d (1H, J1 8.0, J2 1.1), 6.80 d. d (1H,
J1 7.6, J2 1.6), 6.91 d. d. d (1H, С6Н4, J1 8.0, J2 7.4, J3
1.6), 7.25–7.32 and 7.37–7.45 m (5Н, С6Н5), 8.99 (1Н,
ОН). Found, %: С 77.31; Н 6.72; N 9.72. С18Н18N2О.
Calculated, %: С 77.69; Н 6.47; N 10.07.
The IR spectra were obtained on a Specord 75-UR
1
instrument (thin layer). The H NMR spectra were
recorded on a Varian Mercury instrument (300 MHz)
in DMSO-d6 and CDCl3.
After the solvent (CCl4) removal, the residue was
distilled to give 8.9 g (31.4%) of compound V, bp 170°C
(1 mm Hg), nD20 1.5960. IR spectrum, ν, cm–1: 1510
1-Phenyl-3,5-dimethyl-4-chloromethylpyrazole II
was synthesized by a known method [5], bp 160°C (1
mm Hg), nD20 1.5864.
1
(ring), 1580 (Ph). Н NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.32 s (6Н, СН3), 4.85 s (2H, CH2), 7.21–7.45
m (10Н, 2 С6Н5). Found, %: С 77.69; Н 6.47; N 10.07.
С18Н18N2О. Calculated, %: С 77.69; Н 6.47; N 10.07.
2-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-ylmethyl)-
phenol (III), 4-(3,5-dimethyl-1-phenyl-1H-pyrazol-
4-ylmethyl)phenol (IV), 3,5-dimethyl-4-phenoxy-
methyl-1-phenyl-1H-pyrazole (V). A mixture of 9.4 g
of phenol, 4 g of sodium hydroxide, 50 ml of dioxane,
and 1 g of benzyltriethylammonium chloride was
stirred for 0.5 h at 70°C. Then 11.0 g of 1-phenyl-3,5-
dimethyl-4-chloro-methylpyrazol II dissolved in 25 ml
of dioxane was added dropwise within 1 h, and the
stirring was continued for 12 h. After the dioxane
removal, the residue was washed with water and
extracted with chloroform (2×50 ml). After distilling
the chloroform off, to the residue was added 50 ml of
CCl4, and the mixture was kept for 1 day. The resulting
crystals were filtered off. Yield 9.1 g (32.3%),
mp 190–220°C. IR spectrum, ν, cm–1: 1510 (pyrazole),
1590 (Ph), 3200–3400 (OH). The ratio of ortho- (III)
and para-isomers (IV) is 9:1 (1H NMR). Recrys-
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 8 2011