2，3，5-三甲基吡嗪的合成研究
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摘要
本论文研究以异丙醇胺为原料经催化氨化合成1,2-丙二胺的方法,考察了Raney Ni催化剂用量、原料配比、反应温度、反应时间和氢气加入量对实验结果的影响。确定了合成1,2-丙二胺的最佳反应条件:Raney Ni催化剂用量为异丙醇胺质量的4%,异丙醇胺与氨气的物质的量比为1:3.5,反应温度为160℃,氢气加入量与原料异丙醇胺的物质的量之比为1:5,反应时间为5h。1,2-丙二胺收率在90.3%以上,纯度99.5%以上。大大减少了工业三废的排放量,探索出了一条绿色的合成工艺。
以1,2-丙二胺和2,3-丁二酮为原料经缩合氧化合成了2,3,5-三甲基吡嗪,分别考察了影响缩合反应和氧化反应的各种因素,确定了缩合反应的最佳条件为:将原料2,3-丁二酮溶于乙醇(2,3-丁二酮与乙醇的质量比为1:5),匀速滴加到1,2-丙二胺的乙醇溶液(1,2-丙二胺与乙醇质量比为1:6)中,滴加时间3h,反应温度为-5℃,1,2-丙二胺与2,3-丁二酮的物质的量比为1.1:1。最佳的脱氢氧化反应条件为:以空气做氧化剂,氢氧化钾与2,3,5-三甲基-5,6-二氢吡嗪的物质的量比为3:1,乙醇与2,3,5-三甲基-5,6-二氢吡嗪的质量比10:1,反应温度68℃,反应时间7h,两步反应的总收率为83.0%,产物2,3,5-三甲基吡嗪的纯度可达99.5%。
1,2-Diaminopropane was synthesized by amination of isopropanolamine in the presence of ammonia and a hydrogenation catalyst Raney Ni.The effect of the amount of Raney Ni catalyst,the molar ratio of materials,reaction temperature and reaction time on the experiment were studied.The optimum conditions were as follows:the amount of catalyst used was 4%by weight of the amount of isopropanolamine used,the molar ratio of isopropanolamine to ammomia was 1:3.5,the reaction temperature was 160℃,the reaction was 5h,the molar ratio of hydrogen to isopropanolamine was 1:5.Yield of 1,2-diaminopropane as high as 89%was obtainable and the purity is above 99.5%.The green synthesis technology with very little emission was developed.
Synthesis of 2,3,5-trimethylpyrazine from 2,3-butanedione and 1,2-diaminopropane through 2,3,5-trimethyl-5,6-dihydropyrazine was studied.The reaction was comprised of synthesis of 2,3,5-trimethyl-5,6-dihydropyrazine and 2,3,5-trimethylpyrazine.(1) The optimum conditions of 2,3,5-trimethyl-5,6-dihydropyrazine synthesis were established: 2,3-butanedione which was mixed with anhydrous ethyl alcohol(the mass ratio of anhydrous ethyl alcohol to 2,3-butanedione was 5:1) was droped to the mixture of anhydrous ethyl alcohol and 1,2-diaminopropane(the mass ratio of anhydrous ethyl alcohol to 1,2-diaminopropane was 6:1) at the even pace for 3h,the molar ratio of 2,3-butanedione to 1,2-diaminopropane was 1:1.1,the condensation reaction temperature was -5℃.(2) The best dehydrogen oxidation conditions were as follows:air was used as oxidant,the molar ratio of potassium hydroxide and 2,3,5-Trimethyl-5,6-dihydro-pyrazine was 3:1,the mass ratio of ethanol to 2,3,5-trimethyl-5,6-dihydro-pyrazine 10:1,reaction temperature 68℃,reaction time 7h,the total yield of this two-step reaction was 83.0%.
以1,2-丙二胺和2,3-丁二酮为原料经缩合氧化合成了2,3,5-三甲基吡嗪,分别考察了影响缩合反应和氧化反应的各种因素,确定了缩合反应的最佳条件为:将原料2,3-丁二酮溶于乙醇(2,3-丁二酮与乙醇的质量比为1:5),匀速滴加到1,2-丙二胺的乙醇溶液(1,2-丙二胺与乙醇质量比为1:6)中,滴加时间3h,反应温度为-5℃,1,2-丙二胺与2,3-丁二酮的物质的量比为1.1:1。最佳的脱氢氧化反应条件为:以空气做氧化剂,氢氧化钾与2,3,5-三甲基-5,6-二氢吡嗪的物质的量比为3:1,乙醇与2,3,5-三甲基-5,6-二氢吡嗪的质量比10:1,反应温度68℃,反应时间7h,两步反应的总收率为83.0%,产物2,3,5-三甲基吡嗪的纯度可达99.5%。
1,2-Diaminopropane was synthesized by amination of isopropanolamine in the presence of ammonia and a hydrogenation catalyst Raney Ni.The effect of the amount of Raney Ni catalyst,the molar ratio of materials,reaction temperature and reaction time on the experiment were studied.The optimum conditions were as follows:the amount of catalyst used was 4%by weight of the amount of isopropanolamine used,the molar ratio of isopropanolamine to ammomia was 1:3.5,the reaction temperature was 160℃,the reaction was 5h,the molar ratio of hydrogen to isopropanolamine was 1:5.Yield of 1,2-diaminopropane as high as 89%was obtainable and the purity is above 99.5%.The green synthesis technology with very little emission was developed.
Synthesis of 2,3,5-trimethylpyrazine from 2,3-butanedione and 1,2-diaminopropane through 2,3,5-trimethyl-5,6-dihydropyrazine was studied.The reaction was comprised of synthesis of 2,3,5-trimethyl-5,6-dihydropyrazine and 2,3,5-trimethylpyrazine.(1) The optimum conditions of 2,3,5-trimethyl-5,6-dihydropyrazine synthesis were established: 2,3-butanedione which was mixed with anhydrous ethyl alcohol(the mass ratio of anhydrous ethyl alcohol to 2,3-butanedione was 5:1) was droped to the mixture of anhydrous ethyl alcohol and 1,2-diaminopropane(the mass ratio of anhydrous ethyl alcohol to 1,2-diaminopropane was 6:1) at the even pace for 3h,the molar ratio of 2,3-butanedione to 1,2-diaminopropane was 1:1.1,the condensation reaction temperature was -5℃.(2) The best dehydrogen oxidation conditions were as follows:air was used as oxidant,the molar ratio of potassium hydroxide and 2,3,5-Trimethyl-5,6-dihydro-pyrazine was 3:1,the mass ratio of ethanol to 2,3,5-trimethyl-5,6-dihydro-pyrazine 10:1,reaction temperature 68℃,reaction time 7h,the total yield of this two-step reaction was 83.0%.
引文
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[44]罗铁军.2,3-二甲基吡嗪和2,3,5-三甲基吡嗪的合成[J].湖南化工,1998,8(1):25-26.
[45]许良忠,殷树梅,陈青等.新型食用香料2,3,5-三甲基吡嗪的合成[J].山东化工,1997(2):15-16.
[46]李谦和,尹笃林,伏再辉.2,3,5-三甲基吡嗪生产新工艺的研究[J].精细石油化工,1998(1):19-21.
[47]Akiyama J;Enomoto R;Shibamoto P.A New Method of Pyrazine Synthesis for Flavor Use[J].J Agric Food Chem,1978,26(5):1315-1319.
[48]An Adams;Norbert De Kimpe.Formation of Pyrazine and 2-Acetyl-1-pyrroline by Bacillus[J].Food Chemistry,2007(101):1230-1238.
[49]Langdon William K.Method for Preparing Alkyl-substituted Piperazines and Mixtures[P].US 3067199,1962-07-11.
[50]白国义,孙春玲,李阳.正丁醇催化胺化合成正丁胺反应的研究[J].化学推进剂与高分子材料,2002(86):30-34.
[51]王积涛等.高等有机化学[M].北京:高等教育出版社,1979.
[2]Bartkowiak M;Milchert E.The Properties and Applications of 1,2-Propylenediamine and Polypropyleneamines[J].Przem Chem,2003(82):277-281.
[3]Domanska Aleksandra;Ropuszynski Stanislaw.Properties and Applieation of 1,2-Propylenediamine[J].Prate Naukowe Instytutu Yeehnology Organieznej Tworzyw Sztucznych Politechniki Wroelawskiej,1977(23):49-61.
[4]Zienko Jaroslaw;Milchert Eugeniusz;Myszkowski Jerzy.Synthesis Method and Uses of Propyleneamines[J].Chemik,1989,42(7):175-177.
[5]全国原料药生产工艺汇编编写组.全国原料药生产工艺汇编[M].北京:国家医药管理总局,1980.
[6]陈磊,王金伟,马天右.丙二胺改性虫胶涂料用于铜表面防腐蚀性能的研究[J].中国涂料,2006(04):22-24.
[7]张建国,曹正祥.二氯丙烷(DCP)氨化合成丙二胺的开发和应用[J].北工科技市场,2000(4):14-16.
[8]聂颖.环氧氯丙烷的生产工艺与改进[J].化工时刊,2004,(7):33-35.
[9]苏玉光.N,N-二甲基-1,3-丙二胺[J].应用化工,1988(2):57-59
[10]邓远平,孙烈刚,胡秀华.2,3,5-三甲基毗嗦生产工艺的改进[J].化工时刊,2002,16(8):51-53.
[11]王玉玲,宋宏锐,宋爱华.丙二胺的拆分及右雷佐生的合成[J].中国药物化学杂,2003,13(2):106-108.
[12]崔青霞,张武,郝允玲等.1,2-丙二胺单Schiff碱镍(Ⅱ)配合物的合成与晶体结构[J].化学研究,2008,19(1):32-35.
[13]崔青霞,张武,郝允玲等.1,2-丙二胺Schiff碱双核铜配合物合成与晶体结构[J].河南大学学报(自然科学版),2007,37(6):590-594.
[14]陈浩龙,蒋琳兰.格列吡嗪缓释片的制备及其体外释放度考察[J].广州医药,2009,40(2):60-62.
[15]周晓映,原淑鸿,张红漫.吡嗪酰胺的不良反应概述[J].2008,19(5):387-389.
[16]连小洁,王松,朱鹤孙.川芎嗪衍生物改性丝素材料体外抗凝血性研究[J].郑州大学学报(工学版),2009,30(1):134-138.
[17]李海波,程碧波,李洪珍等.2,6-二氮基-3,5-二硝基吡嗪-1-氧化物的合成[J].有机化学,2007.27(1):112-115.
[18]R.NotrisShreve L.WRothenberger.Amination in Liquidarnrnonia[J].Industrial And Engineering Chemistry,1967,29(12):1361-1364.
[19]Rodney A;James;Helena,etal.Prparation of Alkylamines by the Ammonolysis of Alkyl Halides[P].US 3389179,1968-06-17.
[20]KimSeok Su;Lee Su Hwan;Lee Sang Gu.Method for Producing 1,2-diaminoPropane using Cu/ZSM-5 as catalyst with high yield[P].KR 100442111B,2004-07-19.
[21]Wright Fowler George.Preparation of Propylenediamine[P].US 2519560,1950-08-12.
[22]Siegfried Winderl;Erich Haarer;Hubert Corr,etal.Production of Diaminoalkanes[P],US 3270059,1966-04-09.
[23]Cesare Barbierl;Heard Joseph R.Continuous Process of Manufacturing Amines with Emulsions[P].US 2113640,1938-12-06.
[24]Cesare Barbierl.Production of Amines by Emulsion Method[P].US 2078555,1937-03-16.
[25]George Wright Fowler;Charleston W Va.Preparation of Propylenediamine[P].US 2519560,1950-08-22.
[26]Shatzmiller,Shimon;Bercoviei Sorin.Use of A-bromo-oxime Ethers in the Synthesis of 1,2-Diamines.Liebigs Annalender Chemie,1992(10):1005-1009.
[27]Moses Cenker;Trenton,etal.Process for Making Pyrazine and Alkylpyrazines[P],US 3005820,1958-07-11.
[28]James Kenneth Dixon;Riverside Conn.Pyrazine[P].US 2400398,1946-08-23.
[29]J A Kemp.Improvements in or relating to the Manufacture of Pyrazine[P].Brit 609924,1948-09-1.
[30]Zed;Eng;Chem;Prod.Res Develop,1964,3(1):11-16.
[31](日)公开特许公报 昭49-30383.
[32](日)公开特许公报 昭51-56479.
[33](日)公开特许公报 昭55-45610.
[34](日)公开特许公报 昭55-122769.
[35]石黑武雄等.药学杂志(日)1971,91(3):4216-4219.
[36](日)公开特许公报 昭49-117480.
[37](日)公开特许公报 昭49-25947.
[38]Sato Kanji.Verfahren Zur Herstellung Von Pyrazine[P].Ger 2722307,1978-06-03.
[39](日)公开特许公报 昭55-50024.
[40]Marion J.Method for Producing Pyrazine[J].Przem Chem,1967,21(10):5-10.
[41]Shauima Z,etal.Flavouring Agent[P].FR 1576580,1969-08-15.
[42]Takuya Akiyama.The Manufacture of Pyrazine[J].J Agric Food Chem,1978,26(5):1176-1179.
[43]Cheema Z;Formaini R,etal.Method for the Preparation of 1,2-Diaminopropane[P].US 3737462,1973-11-07.
[44]罗铁军.2,3-二甲基吡嗪和2,3,5-三甲基吡嗪的合成[J].湖南化工,1998,8(1):25-26.
[45]许良忠,殷树梅,陈青等.新型食用香料2,3,5-三甲基吡嗪的合成[J].山东化工,1997(2):15-16.
[46]李谦和,尹笃林,伏再辉.2,3,5-三甲基吡嗪生产新工艺的研究[J].精细石油化工,1998(1):19-21.
[47]Akiyama J;Enomoto R;Shibamoto P.A New Method of Pyrazine Synthesis for Flavor Use[J].J Agric Food Chem,1978,26(5):1315-1319.
[48]An Adams;Norbert De Kimpe.Formation of Pyrazine and 2-Acetyl-1-pyrroline by Bacillus[J].Food Chemistry,2007(101):1230-1238.
[49]Langdon William K.Method for Preparing Alkyl-substituted Piperazines and Mixtures[P].US 3067199,1962-07-11.
[50]白国义,孙春玲,李阳.正丁醇催化胺化合成正丁胺反应的研究[J].化学推进剂与高分子材料,2002(86):30-34.
[51]王积涛等.高等有机化学[M].北京:高等教育出版社,1979.