连续流微反应器中简单咪唑的制备
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摘要
研究了微反应器中Radziszewski反应连续高效制备咪唑的工艺过程,考察了停留时间、反应温度、甲醛/乙二醛摩尔比、醋酸铵/乙二醛摩尔比、乙二醛浓度及不同氨源等工艺参数对咪唑收率的影响,优化了咪唑合成的工艺路线。以醋酸铵为氨源、压力为1.7 MPa、反应温度为140℃、乙二醛浓度为0.25 mol/L、甲醛/乙二醛摩尔比为1.4、醋酸铵/乙二醛摩尔比为2.0、停留时间为159.4 s的条件下,咪唑收率高达81.6%。此外,探索了所构建的微反应器系统对于2-甲基咪唑、2-乙基咪唑和2-异丙基咪唑的合成过程适用性,并对其合成过程中存在的问题进行了讨论。
Highly efficient process of imidazole synthesis by Radziszewski reaction was explored in a continuous-flow microreactor. Process variables of residence time, reaction temperature, molar ratio of formaldehyde to glyoxal, molar ratio of ammonium acetate to glyoxal, glyoxal concentration, and different ammonia sources on imidazole yield were studied to obtain optimized condition for imidazole synthesis in the continuous-flow microreactor. Under the optimal operating conditions of ammonium acetate as ammonia source, pressure 1.7 MPa, reaction temperature 140℃, glyoxal concentration 0.25 mol/L, molar ratio of formaldehyde to glyoxal 1.4, molar ratio of ammonium acetate to glyoxal 2.0, and residence time 159.4 s, yield of imidazole could be reached to 81.6%. Besides, the continuous-flow microreactor was tentatively investigated for preparation of 2-methylimidazole, 2-ethylimidazole, 2-isopropylimidazole and challenges appeared in the process were discussed.
Highly efficient process of imidazole synthesis by Radziszewski reaction was explored in a continuous-flow microreactor. Process variables of residence time, reaction temperature, molar ratio of formaldehyde to glyoxal, molar ratio of ammonium acetate to glyoxal, glyoxal concentration, and different ammonia sources on imidazole yield were studied to obtain optimized condition for imidazole synthesis in the continuous-flow microreactor. Under the optimal operating conditions of ammonium acetate as ammonia source, pressure 1.7 MPa, reaction temperature 140℃, glyoxal concentration 0.25 mol/L, molar ratio of formaldehyde to glyoxal 1.4, molar ratio of ammonium acetate to glyoxal 2.0, and residence time 159.4 s, yield of imidazole could be reached to 81.6%. Besides, the continuous-flow microreactor was tentatively investigated for preparation of 2-methylimidazole, 2-ethylimidazole, 2-isopropylimidazole and challenges appeared in the process were discussed.
引文
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[19]CHEN Y Z,ZHAO Y C,HAN M,et al.Safe,efficient and selective synthesis of dinitro herbicides via a multifunctional continuous-flow microreactor:one-step dinitration with nitric acid as agent[J].Green Chemistry,2013,15(1):91-94.
[20]CHEN Y Z,SU Y H,JIAO F J,et al.A simple and efficient synthesis protocol for sulfonation of nitrobenzene under solvent-free conditionsvia a microreactor[J].RSC Advances,2012,2(13):5637-5644.
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[22]WIRTH T.Microreactors in Organic Synthesis and Catalysis[M].Weinheim:Wiley-VCH,2008.
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[25]ZHAO Y C,CHEN G W,YUAN Q.Liquid-liquid two-phase mass transfer in the T-junction microchannels[J].AICh E Journal,2007,53(12):3042-3053.
[26]YUE J,CHEN G W,YUAN Q,et al.Hydrodynamics and mass transfer characteristics in gas-liquid flow through a rectangular microchannel[J].Chemical Engineering Science,2007,62(7):2096-2108.
[27]尧超群,乐军,赵玉潮,等.微通道内气-液弹状流动及传质特性研究进展[J].化工学报,2015,66(8):2759-2766.YAO C Q,YUE J,ZHAO Y C,et al.Review on flow and mass transfer characteristics of gas-liquid slug flow in microchannels[J].CIESC Journal,2015,66(8):2759-2766.
[28]SCHULZE H.Imidazole synthesis:US3715365[P].1973-02-06.
[29]MAXUT A,NOZIERE B,FENET B,et al.Formation mechanisms and yields of small imidazoles from reactions of glyoxal with NH4+in water at neutral p H[J].Physical Chemistry Chemical Physics,2015,17(31):20416-20424.
[2]KONG L,LV X,LIN Q,et al.Efficient synthesis of imidazoles from aldehydes and 1,2-diketones under superheating conditions by using a continuous flow microreactor system under pressure[J].Organic Process Research&Development,2010,14(4):902-904.
[3]谢玉艳,施先义.2-甲基咪唑的合成及应用[J].广东化工,2010,37(6):93-94.XIE Y Y,SHI X Y.Synthesis and application of 2-methylimidazole[J].Guangdong Chemical Industry,2010,37(6):93-94.
[4]李京海,王中洋,袁军,等.咪唑及其衍生物合成的研究进展[J].化工中间体,2012,(11):4-8.LI J H,WANG Z Y,YUAN J,et al.Research progress of the synthesis of imidazole and its derivatives[J].Chemical Intermediate,2012,(11):4-8.
[5]伍晓春.咪唑类化合物的合成与应用研究[J].精细与专用化学品,2010,18(7):51-55.WU X C.Study on synthesis and applications of imidazole derivatives[J].Fine and Specialty Chemicals,2010,18(7):51-55.
[6]邢其毅.基础有机化学[M].北京:高等教育出版社,1983:1029.XING Q Y.Fundamental Organic Chemistry[M].Beijing:Higher Education Press,1983:1029.
[7]章思规,辛忠.精细有机化工制备手册[M].北京:科学技术文献出版社,1994:609.ZHANG S G,XIN Z.Handbook of Fine Organic Chemical Preparation[M].Beijing:Scientific and Technical Documentation Press,1994:609.
[8]PHILLIPS M A.The formation of 2-methylbenziminazoles[J].Journal of the Chemical Society(Resumed),1928:172-177.
[9]PHILLIPS M A.The formation of 2-substituted benziminazoles[J].Journal of the Chemical Society(Resumed),1928:2393-2399.
[10]WEIDENHAGEN R,HERRMANN R.Eine neue synthese von imidazol-derivaten[J].European Journal of Inorganic Chemistry,1935,68(10):1953-1961.
[11]WEIDENHAGEN R,HERRMANN R,WEGNER H.über neue abk?mmlinge des imidazols(IV.Mitteil.über Imidazole)[J].European Journal of Inorganic Chemistry,1937,70(3):570-583.
[12]刘纪寿,王珏.2-甲基咪唑的合成[J].中国医药工业杂志,1989,20(5):237.LIU J S,WANG J.Synthesis of 2-methylimidazole[J].Chinese Journal of Pharmaceuticals,1989,20(5):237.
[13]高学民,缪留福,李向欣.N-甲基咪唑的制备[J].化学试剂,1992,14(4):248-248.GAO X M,LIAO L F,LI X X.Preparation of N-methylimidazole[J].Chemical Reagents,1992,14(4):248-248.
[14]张平,汤琳,张婷,等.N-甲基咪唑合成工艺研究[J].安徽科技学院学报,2016,50(2):71-75.ZHANG P,TANG L,ZHANG T,et al.Research on the synthetic technology of N-methylimidazole[J].Journal of Anhui Science and Technology University,2016,50(2):71-75.
[15]于宏伟,施继成.1-烃基咪唑的合成[J].精细石油化工进展,2014,15(4):48-50.YU H W,SHI J C.Synthesis of 1-alkylimidazole[J].Advances in Fine Petrochemicals,2014,15(4):48-50.
[16]钱永,杨海,王建军,等.咪唑的合成工艺改进[J].化工中间体,2012,09(4):49-52.QIAN Y,YANG H,WANG J J,et al.Improvement on the synthesis of imidazole[J].Chemical Intermediate,2012,09(4):49-52.
[17]杨卉,丁一刚,杨昌炎,等.咪唑合成工艺优化[J].武汉工程大学学报,2011,33(11):19-22.YANG H,DING Y G,YANG C Y,et al.Optimization for synthesis of imidazole[J].Journal of Wuhan Institute of Technology,2011,33(11):19-22.
[18]孟江平,徐强,宋仲容,等.微波辅助合成咪唑类化合物的研究[J].重庆高教研究,2011,30(3):42-45.MENG J P,XU Q,SONG Z R,et al.Research on microwave-assisted synthesis of imidazole derivatives[J].Chongqing Higher Education Research,2011,30(3):42-45.
[19]CHEN Y Z,ZHAO Y C,HAN M,et al.Safe,efficient and selective synthesis of dinitro herbicides via a multifunctional continuous-flow microreactor:one-step dinitration with nitric acid as agent[J].Green Chemistry,2013,15(1):91-94.
[20]CHEN Y Z,SU Y H,JIAO F J,et al.A simple and efficient synthesis protocol for sulfonation of nitrobenzene under solvent-free conditionsvia a microreactor[J].RSC Advances,2012,2(13):5637-5644.
[21]SHEN J N,ZHAO Y C,CHEN G W,et al.Investigation of nitration processes of iso-octanol with mixed acid in a microreactor[J].Chinese Journal of Chemical Engineering,2009,17(3):412-418.
[22]WIRTH T.Microreactors in Organic Synthesis and Catalysis[M].Weinheim:Wiley-VCH,2008.
[23]DIETRICH T R.Microchemical Engineering in Practice[M].Hoboken,NJ:John Wiley&Sons,2011.
[24]NO?L T,SU Y H,HESSEL V.Beyond organometallic flow chemistry:the principles behind the use of continuous-flow reactors for synthesis[J].Topics in Organometallic Chemistry,2015,9(1):27-35.
[25]ZHAO Y C,CHEN G W,YUAN Q.Liquid-liquid two-phase mass transfer in the T-junction microchannels[J].AICh E Journal,2007,53(12):3042-3053.
[26]YUE J,CHEN G W,YUAN Q,et al.Hydrodynamics and mass transfer characteristics in gas-liquid flow through a rectangular microchannel[J].Chemical Engineering Science,2007,62(7):2096-2108.
[27]尧超群,乐军,赵玉潮,等.微通道内气-液弹状流动及传质特性研究进展[J].化工学报,2015,66(8):2759-2766.YAO C Q,YUE J,ZHAO Y C,et al.Review on flow and mass transfer characteristics of gas-liquid slug flow in microchannels[J].CIESC Journal,2015,66(8):2759-2766.
[28]SCHULZE H.Imidazole synthesis:US3715365[P].1973-02-06.
[29]MAXUT A,NOZIERE B,FENET B,et al.Formation mechanisms and yields of small imidazoles from reactions of glyoxal with NH4+in water at neutral p H[J].Physical Chemistry Chemical Physics,2015,17(31):20416-20424.