2-氰基吡嗪的合成研究
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摘要
本文对吡嗪类化合物在医药、农药、香料等领域中的用途进行了简单的介绍，对目的产物2—氰基吡嗪研发态势、市场前景及意义进行了论述，并综述了2—氰基吡嗪和2—甲基吡嗪的文献合成方法。
首先以乙二胺与1，2—丙二醇为原料，在固定床反应器中反应合成2-甲基吡嗪。用含CuO 41.26％，ZnO 41.79％，Al_2O_3 7.75％的KB-207型催化剂，分别改变反应温度、原料液配比、载气用量，得出这些工艺条件对收率的影响，实验表明，催化剂不经过活化，原料液中含水分40％时可得到较好的转化率和收率，反应温度380℃，最高收率可达68％。并对这种催化剂进行了稳定性实验。
接着以2—甲基吡嗪为原料，进行气相氨氧化催化合成2—氰基吡嗪的实验。分别用自制的三种催化剂进行了工艺研究。其中Mo_xP_yO_zXY型催化剂选择性为60％左右，收率可达40％以上，最合适的工艺条件是反应温度370℃，2—甲基吡嗪：氨气：氧气=1：2.5～3：6(摩尔比)。Sb_2O_3-V_2O_5-TiO_2/SiO_2型催化剂，反应温度380℃，2—甲基吡嗪：氨气：氧气=1：3～6：8.5(摩尔比)，选择性在70％以上，收率可达55％以上，并进行了催化剂稳定性实验，证明该催化剂具有较好的稳定性。
The uses of pyrazine derivatives in pharmaceutical products, agricultural chemicals and spices were introduced in this thesis. The research situation, market foreground and research purpose of the goal product cyanopyrazine were discussed. We also summarized the methods of sythesis of cyanopyrazine and 2-methylpyrazine.
First, ethylenediamine and 1,2-dihydroxypropane were chosen as raw materials to prepare 2-methylpyrazine with the method of catalytic action. The catalyst was KB-207 made by Sichuan Lianya, which compounds CuO 41.26%, ZnO 41.79%, Al2O3 7.75%. The reaction was preceded in fixed bed catalytic reactor. The effects of temperature, ratio of feeds, the carrier gas's use level on the yield were studied. The experiments showed, when the temperature was about 380 , catalyst was not activated, 40% water was used in the feed fluid, the high rate of conversion and yield can be get. The highest yield is 68%. Then ammoxidation catalytic synthesis of cyanopyrazine was studied with the raw material 2-methylpyrazine. We studied the process conditions with use of three kinds of catalysts made by ourselves. The yield can get more than 40% when use the catalyst MoxPyOzXY. The best process condition is temperature 370 , 2-methylpyrazine: ammonia: oxygen= 1:2.5-3:6 (mole ratio). When Sb2O3-V2O5-TiO2/SiO2 catalyst was used, the yield can be 55%, the selectivity is more than 70%. When the temperature was 380 , 2-methylpyrazine: ammonia: oxygen= 1:3 -6:8.5 (mole ratio). The experiments on stability of the catalyst were also done and the result shows that this catalyst is stable.
首先以乙二胺与1，2—丙二醇为原料，在固定床反应器中反应合成2-甲基吡嗪。用含CuO 41.26％，ZnO 41.79％，Al_2O_3 7.75％的KB-207型催化剂，分别改变反应温度、原料液配比、载气用量，得出这些工艺条件对收率的影响，实验表明，催化剂不经过活化，原料液中含水分40％时可得到较好的转化率和收率，反应温度380℃，最高收率可达68％。并对这种催化剂进行了稳定性实验。
接着以2—甲基吡嗪为原料，进行气相氨氧化催化合成2—氰基吡嗪的实验。分别用自制的三种催化剂进行了工艺研究。其中Mo_xP_yO_zXY型催化剂选择性为60％左右，收率可达40％以上，最合适的工艺条件是反应温度370℃，2—甲基吡嗪：氨气：氧气=1：2.5～3：6(摩尔比)。Sb_2O_3-V_2O_5-TiO_2/SiO_2型催化剂，反应温度380℃，2—甲基吡嗪：氨气：氧气=1：3～6：8.5(摩尔比)，选择性在70％以上，收率可达55％以上，并进行了催化剂稳定性实验，证明该催化剂具有较好的稳定性。
The uses of pyrazine derivatives in pharmaceutical products, agricultural chemicals and spices were introduced in this thesis. The research situation, market foreground and research purpose of the goal product cyanopyrazine were discussed. We also summarized the methods of sythesis of cyanopyrazine and 2-methylpyrazine.
First, ethylenediamine and 1,2-dihydroxypropane were chosen as raw materials to prepare 2-methylpyrazine with the method of catalytic action. The catalyst was KB-207 made by Sichuan Lianya, which compounds CuO 41.26%, ZnO 41.79%, Al2O3 7.75%. The reaction was preceded in fixed bed catalytic reactor. The effects of temperature, ratio of feeds, the carrier gas's use level on the yield were studied. The experiments showed, when the temperature was about 380 , catalyst was not activated, 40% water was used in the feed fluid, the high rate of conversion and yield can be get. The highest yield is 68%. Then ammoxidation catalytic synthesis of cyanopyrazine was studied with the raw material 2-methylpyrazine. We studied the process conditions with use of three kinds of catalysts made by ourselves. The yield can get more than 40% when use the catalyst MoxPyOzXY. The best process condition is temperature 370 , 2-methylpyrazine: ammonia: oxygen= 1:2.5-3:6 (mole ratio). When Sb2O3-V2O5-TiO2/SiO2 catalyst was used, the yield can be 55%, the selectivity is more than 70%. When the temperature was 380 , 2-methylpyrazine: ammonia: oxygen= 1:3 -6:8.5 (mole ratio). The experiments on stability of the catalyst were also done and the result shows that this catalyst is stable.
引文
[1] 何坚，孙宝国。香料化学与工艺学．化学工业出版社，2000：515．
[2] 公开特许公报 昭55-164606(1980)
[3] 公开特许公报 昭55-167266(1980)
[4] 特许公报 昭56-2977(1981)
[5] E. Felderand D.Pitré, in "Analytical Profiles of Drug Substances", (K.Florey Ed.), Academic Press,New York,1983.
[6] 陈浩凡，成志毅．促进经皮给药方法的研究进展[J]．广东药学，2000，10(2)：1．
[7] 王蓉麟，冯续，杜彩霞．气相氨氧化催化合成氰基吡嗪的研究．天然气化工，1993，18(5)：45
[8] O.V. Krylov, "Catalysis by Non Metals", Academic Press, New York,1970.
[9] D.J.Hucknall,"Selective Oxidation of Hydrocarbons",Academic Press,New York,1974.
[10] M.Sittig,"Handbook of Catalyst Manufacture",Noyes Data Corp.,Park Ridge,New Jersey,1978.
[11] L.Forni,"Ammoxidation of 2-Methylpyrazine over Oxide Catalysts", Appl.Catal.1986,20:219.
[12] 金文清，陈金华，顾龙勤等．2—甲基吡嗪氨氧化制2—氰基吡嗪研究．精细化工，2002，19(6)：324．
[l3] Kajiyama Shigeo et al.(Sankyo Chemical Industries Co.,Lid.).2-Cyanopyrazine from 2-methylpyrazine,JP 74-30382(1974).
[14] Bergstein, Wolfgang et al.(Degussa A.-G.).Catalysts for producing 2-cyanopyrazine,DE 3107756(1982).
[15] Lee,Young K.et al.(Korea Research Institute of Chemical Technology,S.Korea) Preparation of Cyanopyrazion,EP 698603(1996).
[16] Uchiumi Hiroshi et al.(Nitro Chem.Ind.CO.Lid.) Production of 2-cyanopyrazion,JP 9-295971(1977).
[17] 济南市轻工研究所，合成食用香料手册．轻工业出版社，740
[18] M.Subrahmanyam,S T Kullkarni,A V Rama,Indian Journal of Chemical Technology,1995,2,237.
[19] 冯续，刘蓓华，高定基，吕建德．吡嗪类化合物的制造方法CN 85105846，1985．
[20] 曲红梅等，2-甲基吡嗪研究进展，化学推进剂与高分子材料，2001，3．
[21] Okada Hisatavo.Pyrazine and alkylpyrazines by the reaction of ethylenediamine and glycols,alobols or monoketones in a gas phase in the presence of alumina catalysts.JP 74025947.1970-11-19.
[22] Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[23] 郭正，吕建明．烟用香精中烷基吡嗪类化合物的合成与应用．烟草科技，1996(3)：4．
[24] 罗铁军．2，3-二甲基吡嗪和2，3，5-三甲基吡嗪的合成．湖南化工，1998，28(1)：25．
[25] 殷伦祥，李来仲，梁芳珍，徐克花．2，3-二甲基吡嗪的合成研究．山东师大学报，1999，14(1)：44．
[26] 李加荣．制备吡嗪类化合物的改进方法．CN 1191220，1997．
[27] 李谦和，尹笃林，伏再辉．2，3-二甲基吡嗪合成工艺的改进．合成化学，1997，5(2)：189．
[28] 黄小凤，李中林，任晓斌．2，3，5-三甲基吡嗪的合成新工艺．精细化工，1993，10：14．
[29] kajiyama Shigeo.pyrazine and lower alkylpyrazines from piperazines.JP 74030383.1972-06-14.
[30] Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[31] 周立山，冯亚青等．2-甲基吡嗪的合成研究．香料香精化妆品，2000(4)：1．
[32] Gitis K M.Alumnium platinium catalysts in synthesis of nitrogen-containing heterocycles catalytic synthesis of pyrazines[J].Khim Geterotsikl Socdin.1993,(11):1515-1525.
[33] 花文廷．杂环化学，第10版，北京：北京大学出版社，1990．
[34] Yasuba Shinichi,JP7410139.1973-02-08;Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[35] 徐克勋．精细有机化工材料及中间体手册．化学工业出版社．4-106．
[36] 周立山，冯亚青等．2-甲基吡嗪合成研究．天津大学学报，2001，34(5)：694．
[37] B．C．盖茨 J．R．卡泽．催化过程的化学．化学工业出版社 1985：356．
[38] John N,et al.Production of Nitriles [P].US:2499055,1950-02-28．
[39] 陈金华 芳香氨氧化技术在精细化工合成中的应用．精细化工，1999，16(5)：6．
[2] 公开特许公报 昭55-164606(1980)
[3] 公开特许公报 昭55-167266(1980)
[4] 特许公报 昭56-2977(1981)
[5] E. Felderand D.Pitré, in "Analytical Profiles of Drug Substances", (K.Florey Ed.), Academic Press,New York,1983.
[6] 陈浩凡，成志毅．促进经皮给药方法的研究进展[J]．广东药学，2000，10(2)：1．
[7] 王蓉麟，冯续，杜彩霞．气相氨氧化催化合成氰基吡嗪的研究．天然气化工，1993，18(5)：45
[8] O.V. Krylov, "Catalysis by Non Metals", Academic Press, New York,1970.
[9] D.J.Hucknall,"Selective Oxidation of Hydrocarbons",Academic Press,New York,1974.
[10] M.Sittig,"Handbook of Catalyst Manufacture",Noyes Data Corp.,Park Ridge,New Jersey,1978.
[11] L.Forni,"Ammoxidation of 2-Methylpyrazine over Oxide Catalysts", Appl.Catal.1986,20:219.
[12] 金文清，陈金华，顾龙勤等．2—甲基吡嗪氨氧化制2—氰基吡嗪研究．精细化工，2002，19(6)：324．
[l3] Kajiyama Shigeo et al.(Sankyo Chemical Industries Co.,Lid.).2-Cyanopyrazine from 2-methylpyrazine,JP 74-30382(1974).
[14] Bergstein, Wolfgang et al.(Degussa A.-G.).Catalysts for producing 2-cyanopyrazine,DE 3107756(1982).
[15] Lee,Young K.et al.(Korea Research Institute of Chemical Technology,S.Korea) Preparation of Cyanopyrazion,EP 698603(1996).
[16] Uchiumi Hiroshi et al.(Nitro Chem.Ind.CO.Lid.) Production of 2-cyanopyrazion,JP 9-295971(1977).
[17] 济南市轻工研究所，合成食用香料手册．轻工业出版社，740
[18] M.Subrahmanyam,S T Kullkarni,A V Rama,Indian Journal of Chemical Technology,1995,2,237.
[19] 冯续，刘蓓华，高定基，吕建德．吡嗪类化合物的制造方法CN 85105846，1985．
[20] 曲红梅等，2-甲基吡嗪研究进展，化学推进剂与高分子材料，2001，3．
[21] Okada Hisatavo.Pyrazine and alkylpyrazines by the reaction of ethylenediamine and glycols,alobols or monoketones in a gas phase in the presence of alumina catalysts.JP 74025947.1970-11-19.
[22] Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[23] 郭正，吕建明．烟用香精中烷基吡嗪类化合物的合成与应用．烟草科技，1996(3)：4．
[24] 罗铁军．2，3-二甲基吡嗪和2，3，5-三甲基吡嗪的合成．湖南化工，1998，28(1)：25．
[25] 殷伦祥，李来仲，梁芳珍，徐克花．2，3-二甲基吡嗪的合成研究．山东师大学报，1999，14(1)：44．
[26] 李加荣．制备吡嗪类化合物的改进方法．CN 1191220，1997．
[27] 李谦和，尹笃林，伏再辉．2，3-二甲基吡嗪合成工艺的改进．合成化学，1997，5(2)：189．
[28] 黄小凤，李中林，任晓斌．2，3，5-三甲基吡嗪的合成新工艺．精细化工，1993，10：14．
[29] kajiyama Shigeo.pyrazine and lower alkylpyrazines from piperazines.JP 74030383.1972-06-14.
[30] Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[31] 周立山，冯亚青等．2-甲基吡嗪的合成研究．香料香精化妆品，2000(4)：1．
[32] Gitis K M.Alumnium platinium catalysts in synthesis of nitrogen-containing heterocycles catalytic synthesis of pyrazines[J].Khim Geterotsikl Socdin.1993,(11):1515-1525.
[33] 花文廷．杂环化学，第10版，北京：北京大学出版社，1990．
[34] Yasuba Shinichi,JP7410139.1973-02-08;Korea research institute of chemical technology.Preparation of methylpyrazine.JP 02184679.1990-07-19.
[35] 徐克勋．精细有机化工材料及中间体手册．化学工业出版社．4-106．
[36] 周立山，冯亚青等．2-甲基吡嗪合成研究．天津大学学报，2001，34(5)：694．
[37] B．C．盖茨 J．R．卡泽．催化过程的化学．化学工业出版社 1985：356．
[38] John N,et al.Production of Nitriles [P].US:2499055,1950-02-28．
[39] 陈金华 芳香氨氧化技术在精细化工合成中的应用．精细化工，1999，16(5)：6．