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 Abstract: 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. 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 1 H NMR and 13 C 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. * Corresponding author. Fax: +98-7313938. E-mail: fakhraian@yahoo.com. (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. (5) (a) Seitetsu K. Co. Ltd. Jpn. Kokai Tokkyo Koho JP 58 154,561; Chem. 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 Xuebao 1996, 24(1), 16-23; Chem. Abstr. 1996, 125, 58283k. (10) Zhang, S.; Cao, R.; Li, G.; Liu, L. Huaxue Shiji 1993, 15(1), 54; Chem. Abstr. 1993, 119, 95277h. (11) Adaway, T. J.; Kershner, L. D. PCT Int. Appl. WO 97 05,112; Chem. Abstr. 1997, 126, 212052p. Scheme 1. Mechanism pathway for the reaction of 1 with 2 proposed by Pew et al. 8 in the preparation of 6 Organic Process Research & Development 2003, 7, 329-333 10.1021/op025610t CCC: $25.00 © 2003 American Chemical Society Vol. 7, No. 3, 2003 / Organic Process Research & Development • 329 Published on Web 04/03/2003