Organic Process Research & Development 2003, 7, 329−333
Reinvestigation of the Reaction of Trichloroacetyl Chloride and Acrylonitrile in
the Preparation of 3,5,6-Trichloropyridin-2-ol
H. Fakhraian,* A. Moghimi, A. Bazaz, H. Hadj-Ghanbary, and M. Sadeghi
Department of Chemistry, Imam Hossein UniVersity, Tehran, Iran
Scheme 1. Mechanism pathway for the reaction of 1 with
Abstract:
2 proposed by Pew et al.8 in the preparation of 6
The synthesis of 3,5,6-trichloropyridin-2-ol via the CuCl-
catalyzed reaction of trichloroacetyl chloride and acrylonitrile
under both pressure and atmospheric conditions and the
hydrolysis of the reaction mixture were reinvestigated. The
products and byproducts formed in each case, before the
hydrolysis step, were characterized, and the factors causing
their formation are discussed. It was found that two newly
identified byproducts influence the yield of the reaction.
Introduction
3,5,6-Trichloropyridin-2-ol (6) is a valuable intermediate
for the commercial production of chlorpyrifos (Dursban
insecticide) and triclopyr (Garlon herbicide). Different
methods for the preparation of this compound have already
been reported,1-11 among which the CuCl-catalyzed addition
of trichloroacetyl chloride (1) to acrylonitrile (2) is the most
attractive and well-known method for the large-scale produc-
tion of this compound.6-11
The mechanism of this reaction has been studied, and a
three-stepreaction (addition, cyclization, and aromatization
(Scheme 1)) has been proposed.8 2,2,4-Trichloro-4-cyanobu-
tanoyl chloride (3) is produced by the addition of 1 to 2
under atmospheric pressure using a nitrogen stream.8,11 The
cyclization of 3 in the presence of HCl and under pressure
conditions has led to 3,3,5,6-tetrachloro-3,4-dihydropyridin-
2(1H)-one (4) and the hydrolysis of 4 has afforded 6.8
Nevertheless, the reaction of 1 with 2 and the hydrolysis
of the reaction mixture is an attractive method, involving
fewer separation and purification steps; Carrying out this
reaction in the absence of a nitrogen stream has led directly
to 4, and the aromatization of 4 to 6 is performed using a
mineral base (e.g., NaOH).7,9,10
The above-mentioned reaction has also been studied under
pressure conditions, and co-joint formation of 2,3,5,6-
tetrachloropyridine (5) and 6 has been observed.6 The
hydrolysis of 5 to afford 6 has been well documented.5
Although considerable attention has been paid to the major
products formed under different reaction conditions, the
nature of the byproducts, as a limiting factor that affects the
yield of target product 6, has not been studied and discussed
in detail yet. In this contribution, we propose the mechanism
of the reaction of 1 with 2 under both pressure and
atmospheric conditions in more detail. Considering the
mechanism, we also introduce the optimized conditions to
minimize the byproducts.
(1) Rigterink, R. H. U.S. Patent 3,244, 586; Chem. Abstr. 1966, 65, 681e.
(2) Rigterink, R. H.; Kenega, E. E. J. Agric. Food Chem. 1966, 14, 4(3), 304-
306.
(3) Orth, W. Ger. Offen. DE 3, 308,800; Chem. Abstr. 1951, 45, 8013f.
(4) Hertog H. J.; de Bruyn, J. Recl. TraV. Chim. Pays-Bas 1951, 70, 182-
190.
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Abstr. 1984, 100, 120891w. (b) Yamagiwa, S.; Takabe, A. Jpn. Kokai
Tokkyo Koho JP 62 39,570; Chem. Abstr. 1987, 107, 58877k. (c) Shishido,
S.; Sanada, H.; Noda, S. Jpn. Kokai Tokkyo Koho JP 63 313,771; Chem.
Abstr. 1989, 110, 154165j. (d) Kamei, N. Jpn. Kokai Tokkyo Koho JP 01
68,357; Chem. Abstr. 1989, 111, 115051v. (e) Kamei, N. Jpn. Kokai Tokkyo
Koho JP 01 203,364; Chem. Abstr. 1990, 112, 55624t. (f) Kamei, N.;
Nishiwaki, F. Jpn. Kokai Tokkyo Koho JP 01 203,363; Chem. Abstr. 1990,
112, 76966w.
(6) Martin, P. Eur. Pat. Appl. 30,214; Chem. Abstr. 1981, 95, 150459g.
(7) Martinuzzi, E. A.; Colonna, A. O. Braz. Pedido PI BR 87 03,983; Chem.
Abstr. 1989, 111, 97100d.
(8) Pew, G. R. Eur. Pat. Appl. EP 397,281; Chem. Abstr. 1991, 114, 164019m.
Pew, G. R.; Gall, J. A. J. Org. Chem. 1994, 59, 9(22), 6783-6785.
(9) Xu, D.; Xu, Z.; Dai, J.; Chen, M.; Zhang, M. Zhejiang Gongye Daxue
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Abstr. 1993, 119, 95277h.
Results and Discussion
The CuCl-catalyzed reaction of 1 with 2 was performed
under both pressure and atmospheric conditions. The reaction
mixture components were separated and characterized by 1H
NMR and 13C NMR spectroscopy (see Experimental Sec-
tion). In addition to reactant 2, four products (3, 4, 5, and 6)
and two byproducts (7 and 8) have been recognized, the
amounts of which depend on the reaction conditions, as
summarized in Scheme 2 and Table 1. The different
approaches to convert each of the products 3, 4, and 5 to
the main product (6) are stated above.
(11) Adaway, T. J.; Kershner, L. D. PCT Int. Appl. WO 97 05,112; Chem. Abstr.
1997, 126, 212052p.
10.1021/op025610t CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/03/2003
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