3，5，6-三氯吡啶-2-醇钠合成实验和工艺研究
摘要
3，5，6-三氯吡啶-2-醇钠(简称三氯吡啶醇钠)是一种重要的化工原料和性能优良的螯合浮选剂，更是合成多种农药的重要中间体，特别是用于生产广谱有机磷杀虫杀螨剂毒死蜱。
三氯吡啶醇钠的合成路线按起始原料分主要有吡啶法、三氯乙酰氯法、三氯乙酸苯酯法和丙烯酸法，其中以三氯乙酰氯和丙烯腈为原料，氯化亚铜为催化剂是该产品合成的主要路线。国内外均有关于这一路线合成工艺条件研究的论文和专利发表。从文献报道来看，该路线合成三氯吡啶醇钠的收率多在50～70％之间。
浙江新安化工集团股份有限公司已有一套1000吨／年的毒死蜱生产装置，采用以三氯乙酰氯和丙烯腈为原料的常压一锅法生产三氯吡啶醇钠，但其收率一直较低(平均在56％以下)，迫切需要提高收率以降低最终产品毒死蜱的生产成本，提高其品质和增强市场竞争能力。
从结构上看，以三氯乙酰氯和丙烯腈为原料合成三氯吡啶醇钠包括加成、环化和芳构化三个反应过程。其中以加成反应最为关键，它不仅是最慢的过程，其收率的多少也决定了目的产品三氯吡啶醇钠含量的高低，是整个过程的关键步骤。
本文首先对各步反应的历程进行了研究，把握各步反应的一般特性和规律，重点分析其决定作用的关键过程；其次考察了反应温度、压力、时间，催化剂的种类和助催化剂的选择，溶剂和助溶剂的选择以及各原料之间的配比等因素对三氯吡啶醇钠合成收率和含量的影响。确定了最优的工艺控制指标，并创新性的提出在环化反应中增加降温过程，将丙烯腈的投料方式由一次性加入改为连续滴加或分批加入，最终使三氯吡啶醇钠的合成收率由原来的56％左右提高至65％以上。
Sodium 3,5,6-trichloropyridin-2-ol is an important chemical material, chelating floating agent of choiceness performance, main intermediate for synthesizing several herbicides, fungicides, and insecticides, for example, the organic phosphorus insecticide O-O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate.
According to the original material, the method for producing trichloropyridinol sodium including pyridine route, acrylic acid way, benzene trichloroacetate and trichloroacetyl chloride way etc. However, trichloroacetyl chloride technology is adopt broadly at home. A great deal of thesis and patents on the synthesis technique of trichloropyridinol sodium which using trichloroacetyl chloride (TCAC) and acrylonitrile (VCN) had been published over the seas. From the literature, the yield of product is mostly 50 percent to 70 percent.
Zhejiang xin'an chemical co., Ltd. has a set of lOOOt/a production devices of chlorpyrifos which using TCAC and VCN to synthesize trichloropyridinol sodium at atmospheric pressure. Whereas, the yield of trichloropyridinol sodium which is always under 56 percent. In order to reduce the producing cost and enhance competition of market of chlorpyrifos , it is essential to improve the yield of trichloropyridinol sodium.
See from the structure, the'process which to synthesize trichloropyridinol sodium with TCAC and VCN including Addition, Cyclization and Aromatization. Among the three steps, Addition reaction is the crucial step in that it is not only the slowest process but also how much its yield decides stand or fall of content of trichloropyridinol sodium.
The thesis mastered the general characteristic and rule, analyzing especially the crucial process that is decisively from the principle of every step at first. In the second, the paper discussed the following factors such as reaction temperature, pressure, times, the kind of catalyst or co-catalyst, and the kind of solvent or co-solvent, and proportion of all kinds of materials and so on, which is how to influence the yield and content of trichloropyridinol sodium. At last, the thesis brought forward optional control parameters of technology;' Innovatively add a process of reducing temperature in the Cyclization. Changing the manner joining of acrylonitrile from join-one-off to titration or batch. The data of production indicate that the yield of trichloropyridinol sodium has proved over nine percent.
三氯吡啶醇钠的合成路线按起始原料分主要有吡啶法、三氯乙酰氯法、三氯乙酸苯酯法和丙烯酸法，其中以三氯乙酰氯和丙烯腈为原料，氯化亚铜为催化剂是该产品合成的主要路线。国内外均有关于这一路线合成工艺条件研究的论文和专利发表。从文献报道来看，该路线合成三氯吡啶醇钠的收率多在50～70％之间。
浙江新安化工集团股份有限公司已有一套1000吨／年的毒死蜱生产装置，采用以三氯乙酰氯和丙烯腈为原料的常压一锅法生产三氯吡啶醇钠，但其收率一直较低(平均在56％以下)，迫切需要提高收率以降低最终产品毒死蜱的生产成本，提高其品质和增强市场竞争能力。
从结构上看，以三氯乙酰氯和丙烯腈为原料合成三氯吡啶醇钠包括加成、环化和芳构化三个反应过程。其中以加成反应最为关键，它不仅是最慢的过程，其收率的多少也决定了目的产品三氯吡啶醇钠含量的高低，是整个过程的关键步骤。
本文首先对各步反应的历程进行了研究，把握各步反应的一般特性和规律，重点分析其决定作用的关键过程；其次考察了反应温度、压力、时间，催化剂的种类和助催化剂的选择，溶剂和助溶剂的选择以及各原料之间的配比等因素对三氯吡啶醇钠合成收率和含量的影响。确定了最优的工艺控制指标，并创新性的提出在环化反应中增加降温过程，将丙烯腈的投料方式由一次性加入改为连续滴加或分批加入，最终使三氯吡啶醇钠的合成收率由原来的56％左右提高至65％以上。
Sodium 3,5,6-trichloropyridin-2-ol is an important chemical material, chelating floating agent of choiceness performance, main intermediate for synthesizing several herbicides, fungicides, and insecticides, for example, the organic phosphorus insecticide O-O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate.
According to the original material, the method for producing trichloropyridinol sodium including pyridine route, acrylic acid way, benzene trichloroacetate and trichloroacetyl chloride way etc. However, trichloroacetyl chloride technology is adopt broadly at home. A great deal of thesis and patents on the synthesis technique of trichloropyridinol sodium which using trichloroacetyl chloride (TCAC) and acrylonitrile (VCN) had been published over the seas. From the literature, the yield of product is mostly 50 percent to 70 percent.
Zhejiang xin'an chemical co., Ltd. has a set of lOOOt/a production devices of chlorpyrifos which using TCAC and VCN to synthesize trichloropyridinol sodium at atmospheric pressure. Whereas, the yield of trichloropyridinol sodium which is always under 56 percent. In order to reduce the producing cost and enhance competition of market of chlorpyrifos , it is essential to improve the yield of trichloropyridinol sodium.
See from the structure, the'process which to synthesize trichloropyridinol sodium with TCAC and VCN including Addition, Cyclization and Aromatization. Among the three steps, Addition reaction is the crucial step in that it is not only the slowest process but also how much its yield decides stand or fall of content of trichloropyridinol sodium.
The thesis mastered the general characteristic and rule, analyzing especially the crucial process that is decisively from the principle of every step at first. In the second, the paper discussed the following factors such as reaction temperature, pressure, times, the kind of catalyst or co-catalyst, and the kind of solvent or co-solvent, and proportion of all kinds of materials and so on, which is how to influence the yield and content of trichloropyridinol sodium. At last, the thesis brought forward optional control parameters of technology;' Innovatively add a process of reducing temperature in the Cyclization. Changing the manner joining of acrylonitrile from join-one-off to titration or batch. The data of production indicate that the yield of trichloropyridinol sodium has proved over nine percent.
引文
[1] Manclus, J. J. etc. Journal of Agricultural and Food Chemistry, 44 (12):4052-4062(1996).
[2] Frank H. Murphy, Alvin, Tex. Process for producing 2,3,5,6-tetrachloropyridine, US4, 703, 123, Oct. 27, 1987.
[3] Pierre Martin, Process for producing 2,3,5,6-Tetrachloropyridin and 3,5,6-trichloropyridin-2-ol [P]. US4,327,216, Apr. 27, 1982.
[4] Yamaiwa S, Takabe A, Process of the preparation of 3,5,6-trichloro-2-pyridinol as an intermediate for insecticides. JP6239520. Feb. 1987.
[5] Youval shvo, K. far shemaryahu, Israel. Production of 2,3,5,6-tetrachloropyridine. [P]US5, 618, 942. Apr. 8, 1997
[6] The Journal of Organic Chemistry, Vol. 29. pp:2104-2105(1964).
[7] 化工部农药情报中心站，国外农药品种手册，1981。
[8] 农业部农药鉴定所，新编农药手册，1991。
[9] 中国化工学会农药专业委员会第七周年会议论文集，1994。
[10] 徐保明，秦勇，张绍春，单书香，高收率毒死蜱的合成工艺研究，四川化工，1996(4)：1-3．
[11] 张柏青，周曙光，胡军，袁剑峰，毒死蜱的合成研究，Pesticides. Vol.38, No.7(1999):4-6。
[12] 许丹倩，毒死蜱及其中间体的合成述评，浙江化工，1995：4-8。
[13] 秦琪，甲基毒死蜱合成工艺的比较和制备，宁波化工，17-19。
[14] 曹育才，三氯吡啶酚合成及浮选剂定量构效关系研究〔D〕，长沙：中南工业大学矿物工程系，1999。
[15] Manclus，J．J．etc．Journal of Agricultural and Food Chemistry，44(11)：3703-3709(1996)．
[16] Rigerink R H, Kenaga E E，Agr. Agr. Food chem., 1966, 14:304．
[17] Kamei N, Preparation of chloro-2-pyridinols as intermedi ates for insecticides, JP01203363, Aug. 1989.
[18] MARINAK MICHAEL J; SIMONSON JOHN L, Production of polychlorinated pyridine mixtures by liquid phase chlorination of pyridine or pyridine hydroch-Ioride, US4, 515, 953, 1985-05-07.
[19] MARINAK MICHAEL J; SlMONSON JOHN L, Production of polychlorinated pyridine mixtures by liquid phase chlorination of beta-picoline or beta-picoline hydrochloride, US4, 483, 993 1984-11-20.
[20] Kamei N, Prepartion of chloro-2-pyridrnol derivatives as intermediat efor insecticides. JP0168357, Mar. 1989。
[21] Lorraine M K, Walnut C. Process for preparing phosphorothioates and pheny-lphosphorothioates [P]. US3, 907, 815, 1973-05-21.
[22] Becker Y, Preparation of 3,5,6-trichloropyridin-2-ol and its intermediates, EPO, 341, 585, Sep. 1989.
[23] Recueil Trav. Chim. 70. 182 (1951).
[24] 阿加思·皮尤，制备3，5，6-三氯吡啶-2-醇的改进方法〔P〕ZL90102727．8，1995-01-04。
[25] Ger. offen 2,943,433.
[26] 金炼铁，三氯吡啶酚的合成述评，湖北化工，1998年第2期，1-3页。
[27] MARTIN PIERRE; BELLUS DANIEL, 3,3,5-Trichloroglutaric acid imide US4,360,676, 1982-11-23.
[28] Niels Friis. Bekmarksbro; Process for the preparation of 2,3,5,6-tetrac hloropyridine[P] US5,599,939. Feb.4, 1997.
[29] Timothy J. Adsway; Larry D. Kershner. Process for the preparation of 3,3,5-trichloroglutarimide[P] US5,688,953. Nov.18,1997.
[30] Pierre Martin, 3,3,5-trichloroglutaric acid Amine. [P] EPO,030,215, Nov.23.1982
[31] 杨伟，甲基毒死蜱的最新合成工艺，农药，1990年第23卷第3期，51-52页。
[32] 特开昭62-39570(1987)。
[33] 谢思勉等，三氯吡啶醇合成副产物四氯吡啶的转化研究，湖北化工，1996(增刊)：60-61页。
[34] Kawamvra Masao. Preparation of 2-hydroxyhalogeno pyri dine. [P] JP58-154-561,1983-09-14.
[35] Yigal Becket, Tel Aviv, Israel. Production of 3,5,6-trich-loropyridin2-ol and novel intermediates there of [P], US5,017,705. May.21.1991.
[36] Youval shvo. Production of 2,3,5,6-tetrachloropyridine [P]. US5,618,942, Apr.8.1997
[37] Pews G R. Use of chloride ion as a catalyst for dehydrochlorination reaction: The synthesis of 3,5,6-trichoylopyyidin-2-ol [J]. J. org. chem.1994,59, 6783-6785.
[38] Pews R G, Process for the preparation of 3,5,6-trichlorop-yridin-2-ol, EPO,397,281, Sep.1990.
[39] 孙致远 卢建华等，毒死蜱的合成〔J〕，农药，Vol．37，No．4，1998：13-14。
[40] 程春生，汪灿明等，3，5，6-三氯-2-吡啶醇钠的合成，农药，第37卷，第10期(1998)。
[41] GATLING STERLING C, Process for preparing phosphorothioates and phosphates and phosphonothioates and phosphonates. EPO,307,501.1989-03-22.
[42] 许丹倩、徐振元，3，5，6-三氯吡啶-2-酚的合成，浙江工业大学学报，Vol．24，No．1，Mar．1996：16-22。
[43] 曹育才、蒋玉仁等，3，5，6-三氯吡啶-2酚的合成与波谱特征，中南工业大学学报，Vol．31，No．1，Feb．2000。
[44] Winfried Orth, Hassloch, Method for the preparati-on of 3,3,5-trich 1-oro-1H-pyridine-2-on[P], US:4,546,190. Oct.8.1985.
[45] 许丹倩，3，5，6-三氯吡啶-2-酚电位滴定分析方法的研究，Pesticides．Vol．34，No．11，1995。
[46] 张树奎、曹如珍等，3，5，6三氯吡啶-2-酚的合成方法，化学试剂，15(1)，1993：54-56。
[47] Martinuzzi E A, colonna AO, Process for synthesis of Insecticide intermediate of 2-hydroxy-3,5,6-t-richloropyridine, BP: 8703983,Feb. 14. 1989.
[48] 金烁铁、余红杰，三氯吡啶酚及其钠盐的合成，精细化工，Vol．19，No．8，Aug．2002。
[49] 杨浩 肖国民，杀虫剂毒死蜱的合成进展，应用化工，第32卷第2期，2003年4月：9-12。
[50] 三氯吡啶酚的合成新工艺，精细化工经济与技术信息，2002．000(010)．-18-19。
[51] 于忠伟、魏伟，三氯吡啶醇、三氯吡啶醇钠的高效液相色谱分析，农药，第36卷第12期，1997：22-23。
[52] 张上玉，紫外分类光光度法测定三氯吡啶酸钠的含量，浙江化工52-53(1999)。
[53] Takei, G. H. et al. Bull Environ. Contaim. Toxical. 27(6), 842-849(1981).
[54] 潭天恩 麦本熙等，化工原理，化学工业出版社
[55] 化工产品物性数据手册。
[2] Frank H. Murphy, Alvin, Tex. Process for producing 2,3,5,6-tetrachloropyridine, US4, 703, 123, Oct. 27, 1987.
[3] Pierre Martin, Process for producing 2,3,5,6-Tetrachloropyridin and 3,5,6-trichloropyridin-2-ol [P]. US4,327,216, Apr. 27, 1982.
[4] Yamaiwa S, Takabe A, Process of the preparation of 3,5,6-trichloro-2-pyridinol as an intermediate for insecticides. JP6239520. Feb. 1987.
[5] Youval shvo, K. far shemaryahu, Israel. Production of 2,3,5,6-tetrachloropyridine. [P]US5, 618, 942. Apr. 8, 1997
[6] The Journal of Organic Chemistry, Vol. 29. pp:2104-2105(1964).
[7] 化工部农药情报中心站，国外农药品种手册，1981。
[8] 农业部农药鉴定所，新编农药手册，1991。
[9] 中国化工学会农药专业委员会第七周年会议论文集，1994。
[10] 徐保明，秦勇，张绍春，单书香，高收率毒死蜱的合成工艺研究，四川化工，1996(4)：1-3．
[11] 张柏青，周曙光，胡军，袁剑峰，毒死蜱的合成研究，Pesticides. Vol.38, No.7(1999):4-6。
[12] 许丹倩，毒死蜱及其中间体的合成述评，浙江化工，1995：4-8。
[13] 秦琪，甲基毒死蜱合成工艺的比较和制备，宁波化工，17-19。
[14] 曹育才，三氯吡啶酚合成及浮选剂定量构效关系研究〔D〕，长沙：中南工业大学矿物工程系，1999。
[15] Manclus，J．J．etc．Journal of Agricultural and Food Chemistry，44(11)：3703-3709(1996)．
[16] Rigerink R H, Kenaga E E，Agr. Agr. Food chem., 1966, 14:304．
[17] Kamei N, Preparation of chloro-2-pyridinols as intermedi ates for insecticides, JP01203363, Aug. 1989.
[18] MARINAK MICHAEL J; SIMONSON JOHN L, Production of polychlorinated pyridine mixtures by liquid phase chlorination of pyridine or pyridine hydroch-Ioride, US4, 515, 953, 1985-05-07.
[19] MARINAK MICHAEL J; SlMONSON JOHN L, Production of polychlorinated pyridine mixtures by liquid phase chlorination of beta-picoline or beta-picoline hydrochloride, US4, 483, 993 1984-11-20.
[20] Kamei N, Prepartion of chloro-2-pyridrnol derivatives as intermediat efor insecticides. JP0168357, Mar. 1989。
[21] Lorraine M K, Walnut C. Process for preparing phosphorothioates and pheny-lphosphorothioates [P]. US3, 907, 815, 1973-05-21.
[22] Becker Y, Preparation of 3,5,6-trichloropyridin-2-ol and its intermediates, EPO, 341, 585, Sep. 1989.
[23] Recueil Trav. Chim. 70. 182 (1951).
[24] 阿加思·皮尤，制备3，5，6-三氯吡啶-2-醇的改进方法〔P〕ZL90102727．8，1995-01-04。
[25] Ger. offen 2,943,433.
[26] 金炼铁，三氯吡啶酚的合成述评，湖北化工，1998年第2期，1-3页。
[27] MARTIN PIERRE; BELLUS DANIEL, 3,3,5-Trichloroglutaric acid imide US4,360,676, 1982-11-23.
[28] Niels Friis. Bekmarksbro; Process for the preparation of 2,3,5,6-tetrac hloropyridine[P] US5,599,939. Feb.4, 1997.
[29] Timothy J. Adsway; Larry D. Kershner. Process for the preparation of 3,3,5-trichloroglutarimide[P] US5,688,953. Nov.18,1997.
[30] Pierre Martin, 3,3,5-trichloroglutaric acid Amine. [P] EPO,030,215, Nov.23.1982
[31] 杨伟，甲基毒死蜱的最新合成工艺，农药，1990年第23卷第3期，51-52页。
[32] 特开昭62-39570(1987)。
[33] 谢思勉等，三氯吡啶醇合成副产物四氯吡啶的转化研究，湖北化工，1996(增刊)：60-61页。
[34] Kawamvra Masao. Preparation of 2-hydroxyhalogeno pyri dine. [P] JP58-154-561,1983-09-14.
[35] Yigal Becket, Tel Aviv, Israel. Production of 3,5,6-trich-loropyridin2-ol and novel intermediates there of [P], US5,017,705. May.21.1991.
[36] Youval shvo. Production of 2,3,5,6-tetrachloropyridine [P]. US5,618,942, Apr.8.1997
[37] Pews G R. Use of chloride ion as a catalyst for dehydrochlorination reaction: The synthesis of 3,5,6-trichoylopyyidin-2-ol [J]. J. org. chem.1994,59, 6783-6785.
[38] Pews R G, Process for the preparation of 3,5,6-trichlorop-yridin-2-ol, EPO,397,281, Sep.1990.
[39] 孙致远 卢建华等，毒死蜱的合成〔J〕，农药，Vol．37，No．4，1998：13-14。
[40] 程春生，汪灿明等，3，5，6-三氯-2-吡啶醇钠的合成，农药，第37卷，第10期(1998)。
[41] GATLING STERLING C, Process for preparing phosphorothioates and phosphates and phosphonothioates and phosphonates. EPO,307,501.1989-03-22.
[42] 许丹倩、徐振元，3，5，6-三氯吡啶-2-酚的合成，浙江工业大学学报，Vol．24，No．1，Mar．1996：16-22。
[43] 曹育才、蒋玉仁等，3，5，6-三氯吡啶-2酚的合成与波谱特征，中南工业大学学报，Vol．31，No．1，Feb．2000。
[44] Winfried Orth, Hassloch, Method for the preparati-on of 3,3,5-trich 1-oro-1H-pyridine-2-on[P], US:4,546,190. Oct.8.1985.
[45] 许丹倩，3，5，6-三氯吡啶-2-酚电位滴定分析方法的研究，Pesticides．Vol．34，No．11，1995。
[46] 张树奎、曹如珍等，3，5，6三氯吡啶-2-酚的合成方法，化学试剂，15(1)，1993：54-56。
[47] Martinuzzi E A, colonna AO, Process for synthesis of Insecticide intermediate of 2-hydroxy-3,5,6-t-richloropyridine, BP: 8703983,Feb. 14. 1989.
[48] 金烁铁、余红杰，三氯吡啶酚及其钠盐的合成，精细化工，Vol．19，No．8，Aug．2002。
[49] 杨浩 肖国民，杀虫剂毒死蜱的合成进展，应用化工，第32卷第2期，2003年4月：9-12。
[50] 三氯吡啶酚的合成新工艺，精细化工经济与技术信息，2002．000(010)．-18-19。
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