苯并咪唑卡宾源与硒代异氰酸酯的亲核性研究
|
摘要
卡宾自被确认为是一种反应中间体后,就在有机化学中扮演着重要的角色。早期的卡宾多是N-杂环卡宾的金属络合物,但是他们参与的反应比较局限,仅限于金属络合物的研究。直至1991年,稳定的游离N-杂环卡宾被分离出来后,卡宾就已经摆脱只是作为金属配体的地位,在后面的一系列的研究中,发现其在benzoin反应、分子内不对称Stetter反应的催化中都有很突出的表现。
正是因为卡宾的活泼性,其在医药中间体的合成中的作用也越来越凸显出来。在药物中间片段中,苯并咪唑及其衍生物的作用一直都是不可忽视的,以苯并咪唑环构筑的药物分子因为其广泛的生物活性,常用于组胺受体拮抗剂、质子泵抑制剂、抗高血压、抗菌、抗病毒、抗癌、镇痛等药剂上。不仅如此,还在金属防腐、高性能复合材料、染料等各方面都有着很好的作用。本论文对苯并咪唑类化合物的结构、合成、应用、生物活性研究进展进行了综述,利用其卡宾亲核性较强的原理,将不同的硒代异氰酸酯基团引入反应,合成了5种偶极体,再将这5种偶极体与DMAD(丁炔二酸二甲酯)反应,生成了5种螺环化合物,并对反应进行了碱、溶剂和温度三个方面的条件实验,对反应进行了优化。
本论文一共分为4章,第一章是分别介绍卡宾、苯并咪唑类化合物、异氰酸酯类化合物、噻唑类化合物和四嗪类化合物的结构、生成、反应和应用;第二章介绍选题的依据,目的以及意义,第三章和第四章为实验部分,实验部分主要分为3个内容,第一个内容是1,3-二苄基苯并咪唑卡宾源在碱的作用下脱去2-位上的质子,形成1,3-二苄基苯并咪唑卡宾,其与对溴苯硒代异氰酸酯的反应,生成1,3-二苄基-2(对溴苯基硒代酰胺)-苯并咪唑的偶极体,由该偶极体与DMAD反应生成螺环化合物1,3-二苄基-2-(2-对溴苯基亚胺-4,5-二烯二甲酯-3-硒戊环)苯并咪唑,对反应的条件进行了优化;第二个内容是在优化了的条件下变换了苯并咪唑和硒代异氰酸酯的取代,对生成的螺环化合物进行了IR、1HNRM、13CNMR、MS的检测,证明了化合物结构的正确性;第三个内容是对3-苄基-4甲基噻唑卡宾源和3,6-苯基-1,2,4,5-四嗪反应的探索性实验。
Carbenes play an important role in organic chemistry, since it be determined intermediate. In early years, most of carbenes is N-heterocyclic carbene, the reactions about it were limited metal complexes. Until 1991, the first free N-heterocyclic carben was isolated, carbens is not only join metal complexes, but also got a great effect in benzoin reaction, and catalytic in intramolecular asymmetric of stetter reaction.
Because reactive of carbends has very high activity of reaction, it showing the status of pharmaceutical intermediates. Benzimidazole and its derivatives can not be neglected in drug intermediate fragments. Circle of benzimidazole structure many medical molecules are always used in antagonists, proton pump inhibitors, antihypertensive, antiparasitic, antibacterial, antifungal, anticancer and antiviral agents. It also be used in metal corrosion, high performance composites and dye. In this thesis, we have reviewed the recent advance in the studies on the structures, synthetic, applications and biological activity, use of its nucleophilic, take different substituent’selenium with isocyanate in reaction, synthesis 5 dipoles, and reactive with DMAD, reacted 5 spiro compounds,take condition experiment with base, solvent and temperature.
This thesis is divided into four chapters. In the first chapter, introduction the structure, synthetic, application and biological activity of carbenes, benzimidazole compounds, isocyanate compounds, thiazole compounds and tetrazine compounds. The second chapter is talk about the mean of this project and why to do this, the third and fourth chapter is the part of experimental, content include three parts, one part is reaction of 1,3-2 benzyl benzimidazole with bromobenzene seleno-isocyanate, react 1,3-2-benzyl-2(seleno-amidebromophenyl)-benzimidazole dipole, then it reactive with DMAD, got product 1,3-2-benzyl-2-(2-bromoimide-4,5-diendimethyl-3-Se-Ering) benzi -midazole, and optimum reaction conditions. Another part is change the substituent of benzimizole carbine and selenium with isocyanate, and determine them structures through IR, 1HNRM, 13CNMR, MS. Latest part is a experimental exploration of thiazole and tetrazine.
正是因为卡宾的活泼性,其在医药中间体的合成中的作用也越来越凸显出来。在药物中间片段中,苯并咪唑及其衍生物的作用一直都是不可忽视的,以苯并咪唑环构筑的药物分子因为其广泛的生物活性,常用于组胺受体拮抗剂、质子泵抑制剂、抗高血压、抗菌、抗病毒、抗癌、镇痛等药剂上。不仅如此,还在金属防腐、高性能复合材料、染料等各方面都有着很好的作用。本论文对苯并咪唑类化合物的结构、合成、应用、生物活性研究进展进行了综述,利用其卡宾亲核性较强的原理,将不同的硒代异氰酸酯基团引入反应,合成了5种偶极体,再将这5种偶极体与DMAD(丁炔二酸二甲酯)反应,生成了5种螺环化合物,并对反应进行了碱、溶剂和温度三个方面的条件实验,对反应进行了优化。
本论文一共分为4章,第一章是分别介绍卡宾、苯并咪唑类化合物、异氰酸酯类化合物、噻唑类化合物和四嗪类化合物的结构、生成、反应和应用;第二章介绍选题的依据,目的以及意义,第三章和第四章为实验部分,实验部分主要分为3个内容,第一个内容是1,3-二苄基苯并咪唑卡宾源在碱的作用下脱去2-位上的质子,形成1,3-二苄基苯并咪唑卡宾,其与对溴苯硒代异氰酸酯的反应,生成1,3-二苄基-2(对溴苯基硒代酰胺)-苯并咪唑的偶极体,由该偶极体与DMAD反应生成螺环化合物1,3-二苄基-2-(2-对溴苯基亚胺-4,5-二烯二甲酯-3-硒戊环)苯并咪唑,对反应的条件进行了优化;第二个内容是在优化了的条件下变换了苯并咪唑和硒代异氰酸酯的取代,对生成的螺环化合物进行了IR、1HNRM、13CNMR、MS的检测,证明了化合物结构的正确性;第三个内容是对3-苄基-4甲基噻唑卡宾源和3,6-苯基-1,2,4,5-四嗪反应的探索性实验。
Carbenes play an important role in organic chemistry, since it be determined intermediate. In early years, most of carbenes is N-heterocyclic carbene, the reactions about it were limited metal complexes. Until 1991, the first free N-heterocyclic carben was isolated, carbens is not only join metal complexes, but also got a great effect in benzoin reaction, and catalytic in intramolecular asymmetric of stetter reaction.
Because reactive of carbends has very high activity of reaction, it showing the status of pharmaceutical intermediates. Benzimidazole and its derivatives can not be neglected in drug intermediate fragments. Circle of benzimidazole structure many medical molecules are always used in antagonists, proton pump inhibitors, antihypertensive, antiparasitic, antibacterial, antifungal, anticancer and antiviral agents. It also be used in metal corrosion, high performance composites and dye. In this thesis, we have reviewed the recent advance in the studies on the structures, synthetic, applications and biological activity, use of its nucleophilic, take different substituent’selenium with isocyanate in reaction, synthesis 5 dipoles, and reactive with DMAD, reacted 5 spiro compounds,take condition experiment with base, solvent and temperature.
This thesis is divided into four chapters. In the first chapter, introduction the structure, synthetic, application and biological activity of carbenes, benzimidazole compounds, isocyanate compounds, thiazole compounds and tetrazine compounds. The second chapter is talk about the mean of this project and why to do this, the third and fourth chapter is the part of experimental, content include three parts, one part is reaction of 1,3-2 benzyl benzimidazole with bromobenzene seleno-isocyanate, react 1,3-2-benzyl-2(seleno-amidebromophenyl)-benzimidazole dipole, then it reactive with DMAD, got product 1,3-2-benzyl-2-(2-bromoimide-4,5-diendimethyl-3-Se-Ering) benzi -midazole, and optimum reaction conditions. Another part is change the substituent of benzimizole carbine and selenium with isocyanate, and determine them structures through IR, 1HNRM, 13CNMR, MS. Latest part is a experimental exploration of thiazole and tetrazine.
引文
[1]Heimann R B, Kleiman J, Salansky N M. A unified structuralapp roach to linear carbon polytypes[J]. N ature, 1984, 306 (5939): 164-170.
[2]Whittaker A G. Carbon: a new view of its high temperature behavior[J]. Science, 1978, 200 (4343) : 763-767.
[3]Akagi K, N ishiguchi M , Sh irakawa H, et al. One-dimen-sional conjugated carbyne - synthesis and p roperties [M]. Synth, 1987, 17 (123): 557-566.
[4]Kastner J, Kuzmany H, Kavan L, et al. Reductive p reparation of carbine with high yield and in situ Raman scattering study[J]. Macromolecules, 1995, 28: 344-350.
[5]Kijima M, Sakai Y, Shirakawa H. Electrochemical synthesis of carbine catalyzed by nickel complex[J]. Synthesis Met, 1995, 71:1837-1843.
[6]王世华,陈梓云,王茹.碳的线型同素异形体-卡宾研究进展[J].新型炭材料, 1999, 10: 73-79.
[7]Bourissou D, Grerret O, Gabbai P F, et al. Stable carbenes[J]. Chem Rev, 2000,100: 39-91.
[8]Boufatah N,Gellis A, Maldonado J,et al. Efficient microwave-assisted synthesis of new sulfonybenzimidzole-4,7-diones:heterocyclic quinines with potential antitumor activety[J]. Tetrahedron, 2004, 60: 9131-9137.
[9]彭游,陈智勇,刘燕,等.人工沸石:一种微波干法合成2-芳基取代苯并咪唑衍生物的高效催化剂[J].四川大学学报(自然科学版), 2005, 42: 1054-1055.
[10]Lu J, Yang B, Bai Y. Microwave irradiation synthesis of 2-substituted benzimidazoles using PPA as a catalyst under solvent-free condition[J]. Synth. Commun. 2002, 32, 24: 3703-3709.
[11]Lin S, Isome Y, Stewart E, Liu J, et al. Microwave-assisted one step high-throughput synthesis of benzimizole[J]. Tetrahedron Lett, 2006, 47, 17: 2883-2886.
[12]Nadaf R, Siddiqui N S A, Daniel T, et al. Room temperature ionic liquid promoted regioselective synthesis of 2-aryl benzimizoles, benzoxazoles and benzthiazole under ambient conditions[J]. J Mol Catal A: Chem. 2004, 214: 155-160.
[13]Chen C, Chen Y.Liquid-phase synthesis of 2-substituted benzimizoles, benzoxazoles and benzothiazoles[J]. Tetrahedron Lett. 2004, 45: 113-115.
[14]Wang Q, Mao Y, Zhu S. Novel synthesis of 2-per(poly)fluoroalk-1H-benzimidazoles or 2-per(poly)fluoroalkyl benzothiazoles[J]. J. Fluorine Chem.1999, 95: 141-141.
[15]Singh M P, Sasmal S, Lu W Chatterjee M N.Synthetic utility of catalytic Fe(Ⅲ)/Fe(Ⅱ) redox cycling towards fused heterocycles: a facile acess to substituted benzimidazole, bis-benzimidazole and imidazopyridine derivatives[J]. Synthesis, 2000:1380-1390.
[16]Lieu P, Hruno L, Moos H. E.Enantioselective addition of a trefluoromethyl anion to aryl ketones and aldehydes[J]. Synthesis 2003: 1683-1698.
[17]Lurini M, Epifano F, Montanari F,et al. Ytterbium triflate-promoted synthesis of benzimidazole derivatives[J]. Synlett, 2004:1832-1834.
[18]Liu S, Yang L. A simple and efficient procedure for the synthesis of benzimidazoles using air as the oxidant[J]. Tetrahedron Lett. 2005, 46: 4315-4319.
[19]Brain C T, Brunton S A. An intramolecular palladium-catalyzed aryl amination reaction to produce benzimidazole[J]. Tetrahedron Lett. 2002, 43: 1893-1895.
[20]Fonseca T, Gigante B,Gilchrist T.L.A short aynthesis of phenanthro[2,3-d]imdazoles from dehydrobietic acid. Application of the methodology as a convenient route to benzimidazoles[J]. Tetrahedron 2001, 57: 1793-1799.
[21]Harizi A , Zantour H. Ammonium sulfate-magnesium selective reduction of N-2-notrophenylimidates:synthesis of 2-substituted benzimidazoles[J]. Synth. Commun. 2002, 32: 387-392.
[22]刘长令,翟煜翥,张运晓等,防治灰霉病用杀菌剂的开发[J].农药: 2000, 39(3):1-6.
[23]徐扬,王凤山.南瓜胰蛋白酶抑制剂[J].中国新药杂志, 2007, 27(1): 49-51.
[24]李焱,马会强,王玉炉,苯并咪唑及其衍生物合成与应用研究进展[J].有机化学, 2008,28,2: 210-217.
[25]袁勇,周成合,刘嫱,等.新型合成抗菌药物研究进展[J].中国新药杂志, 2-7, 16(5): 343-349.
[26]Andries K, Moeremans M, Gevers T. Substituted benzimidazoles with nanomolar activity against respiratory syncytial vius[J]. Antiviral Res. 2003, 60: 209-219.
[27]宋春泽,周成合,袁勇.磺胺类碳酸酐酶抑制剂研究进展[J].重要新药杂志, 2007, 16(18): 1438-1444.
[28]Migawa M T, Girardet J L, Walker J A. Design, synthesis, and antiviral activity ofα-nucleosides: D-and L-isomers of lyxofuranosyl- and -5-deoxylyxofuranosy benzimidazoles[J]. J.Med. Chem. 1998, 41, 1242-1251.
[29]Porcari A R.,Devivar R V. Kucera, L. S. Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)-2-subsituted-5-6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole. [J]. Med Chem, 1998, 41: 1252-1262.
[30]Biron KK. Antiviral dugs for cytomegalovirus diseases[J]. Anticiral Res, 2006, 71(2-3): 154-163.
[31]高学军,李庆章.苯并咪唑氨基甲酸酯类抗蠕虫药物作用机理研究进展[J].东北农业大学学报, 2004, 35: 492-495.
[32]孟江平,耿荣霞,周成合,苯并咪唑药物研究进展[J],中国新药杂志, 2009, 18, 16: 1505-1514.
[33]毛煜,佘佳红,袁伯俊.苯并咪唑类质子泵抑制剂的药理和临床研究进展[J].中国新药杂志, 2006, 15 (1): 17 - 21.
[34]Labanauskas L K, Brukstus A B, Gaidelis P G. Synthesis and anti-inflammatory activity of some new 1-acyl derivatives of 5,6-diethoxy-2-(methylthio)benzimidazole[J]. Pharm Chem J, 2000, 34, 353-355.
[35] (a) Navarrete V G, Cedillo R, Hernández Campos A.Synthesis and antiparasitic active of 2-(trifluoromethyl)benzimidazole derivatives[J]. Bioorg Med Chem Lett, 2001, 11: 187-190. (b)杨鲁勒,阎世平,白令君.苯并咪唑双铜配合物合成表征和生物活性[J].化学研究与应用, 1995, 7: 28-31.
[36]于克贵,周成合,李东红.大环类药物研究进展[J].中国药学杂志, 2008, 43(7): 481-488.
[37]周晓湘,刘建平.酸洗缓蚀剂的应用研究现状及发展趋势[J].工业水处理, 2002, 22: 16-18, 22.
[38]沈建,余鼎声,庞正智.苯并咪唑化合物作为碳钢缓蚀剂的研究[J].北京化工大学学报, 2005, 32: 110-112.
[39]史志龙,庞正智.新型酮酸酸洗缓蚀剂烷基苯并咪唑的研究[J].北京化工大学学报, 2002, 29: 52-54.
[40]王清华,胡泽祥,娄方等.苯并咪唑的衍生物对润滑油抗磨及抗腐性能的影响[J].润滑与密封, 2001, 26, 22-22: 78-82. (b)王清华,杨官汉.苯并咪唑衍生物抗腐蚀作用机理的研究[J].润滑与密封, 2002, 26: 29-31.
[41]陆伟峰,虞鑫海.聚苯并咪唑树脂的合成及其应用[J].绝缘材料通讯, 2000, 5: 5-9.
[42]Hahn F E, Wittenbecher L, Wan D L et al. Novel 1,2,4-triphosphole, 1,2,3-triphoshetene and azaphospholene derivatives from N-heterocyclic carbenes and phosphaalkynes[J]. Phoshorus, Sulfurand silicon and the Related Elements, 2002,177(6-7): 1863-1867.
[43]蔡志彬,周茂,胡惟笑等.双光气法合成取代苯基异氰酸酯[J].合成化学, 2000(10): 164-166.
[44]俞传明,王亚频,来虎青等.二(-三氯甲基)碳酸酯的应用研究[J].浙江化工, 1998, 29(20): 20-21.
[45]杜晓华,许响声,徐振元.一种安全有效的合成芳基异氰酸酯的方法[J].农药学报, 2002, 12, 4(4): 83-85.
[46]魏文珑,曹桂荣,常宏宏等.固体光气法合成氯代苯基单异氰酸酯[J].应用化学, 2008, 25, 11: 1369-1371.
[47]冯桂荣,张会茹,芳香异氰酸酯的制备方法[J].河北理工学院学报, 2001, 23(4): 66-67.
[48]沈志勇.异氰酸酯合成方法的研析[J] .通化师范学院学, 2004, 25(4): 57-59.
[49]Vrbach Hans.烷基异氰酸酯制备方法[M].农药译丛, 1984,6(1):34-37.
[50]冯桂荣,沈玉龙,劳旺梅.固-液相转移催化法合成对甲基苯异氰酸酯[J].化工进展, 2002, 21(6): 407-409.
[51]Jun H K, Kin J S, No H k, et al. Chitosanasa Co2 agulant for Recovery of Protenaceous Solids From Tofu Wastewater[J]. J Agnc, Food Chem, 1994, 42: 1834-1838.
[52]赵季芝.光气化产品的开发和应用[J].氯碱工业, 1997(12): 35-38.
[53]王长皇.相转移催化技术在农药合成中的应用进展[J],湖北化工, 1991(3): 34-38.
[54] Aguilar E, Meyers A I, Rrinvestigation of a modified Hantzsch thiazole synthesis, Tetrahedron Lett. 1994,35:2473-2476.
[55] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006: 126.
[56] Lobell M, D H G,Grout. Pyruvate decarboxylase: Amolecular modeling study of pyruvate decarboxylation and acyloin formation[J].J Am Chem Soc,1996,118:1867-1872.
[57] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006: 127.
[58] Contant P, Forzy L, Heingartner U, et al. A new convergent synthesis of thiamine hydrochloride[J]. Helv Chim Acta, 1990, 73: 1300-1305.
[59] Ahmed I, Khazi M, Mahajanshetti C S, et al. Synthesis and antimicrobical activity of some 2-(substituted carboxamidomethyl/thyithio)-5-(2-thienyl)-1,3,4-oxadiazole[J]. Indian J Hetercocycli Chem, 2003, 13(1): 87-88.
[60] Kienle M, Dunst C, Knochel P. Oxidative amination of heteroaromatic zinc reagents mediated bu PhI(OAc)2[J]. Org Lett, 2009, 11(22): 5158-5161.
[61] Roush D M, Davis S G, Lutomski K A, et al. Ethynylbenzothiophene pesticides[P]. US 5073564, 1991, 12, 17.
[62] Dekeyser M A, Mcphee D J, Mcdonald P T. Miticidal hydrazine compounds and their intermediates [P]. US 5567723, 1995, 10, 03.
[63]Maienfisch P L, Gsell L, Rindlisbacher A. Synthesis and insecticidal activity of CGA 293, 343-a novel broadspectrum insecticide[J]. Pestic Sci, 1999, 55(3): 351-354.
[64]Maienfisch P L, Huerlimann H, Rindlisbacher A, et al. The discovery of thiamethoxam: a second-generation neonicotinoid [J]. Pest Manag Sci, 2001, 57(2): 165-176.
[65]Uneme H, Iwanaga K, Higuchi N, et al. Synthesis and insecticidal activity of nitroguanidinederivatives[J]. PesticSci, 1999, 55(2): 202-205.
[66]谢心宏,王福久.噻虫啉—一种新的叶面施用杀虫剂[J].农药, 2001, 40(1): 41-42.
[67]Song Y, Kim D S. Fungicidal composition containing n-(α-cyano-2-thenyl) -4-enthyl-2-enthylaylamino-5-thiazole carboxamide(ethaboxam) and as an adjust polyoxyakylene alkye ether [P]. US 2003 020 3949, 2003.
[68]梁芳珍,徐克花,任建成. 2-氨基噻唑缩取代水杨醛Zn(Ⅱ)配合物的合成、表征及抑菌活性[J] .合成化学, 1999,7(2): 121-124.
[69]刘长令.杀虫杀螨剂研究开发的新进展[J].农药,2003, 42(10): 1-4.
[70]Chavez D. 3-3’-Azobis(6-amino-S-tetrazine): A Novel High Nitrogen Energentic Material[J]. Angew Chem, 2000, 39(10): 1791-1793.
[71]Pilgrim K H G,Skiles R D.Tetrazine Herbicid~[P].us 3 860 589,1975.
[72]周茂,蔡志彬,杨忠愚,等.四嗪衍生物的合成及其抗癌性能研究(Ⅰ)-N, N-二苯基-3, 6-二甲基-1, 4-二氢-1, 2, 4, 5-四嗪-1, 4-二甲酰胺[J] .浙江工业大学学报, 1999, 6: 18-21.
[73]饶国武,周欣,杨忠愚,农药四螨嗪合成新工艺[J].农药, 2003, 42, 2:13-14.
[74] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006:389.
[75]董海山.高能量密度材料的发展及对策[J].含能材料, 2004(增刊), 1-11.
[76]Hiskey M, Chavez D. Insenstitive high nitrogen compounds [R]. NRIS No: DE-2001-776133, 2001.
[77]Hiskey M, Chavez D, et al. Progress in high-nitrogen chemistry in explosives, propellants and pyrotechnics [A]. Proc.27th International Pyrotechnics Seminar [C], July 16～21, USA: Colorado, 2000: 3 - 14.
[78]Hiskey M, Chavez D , et al. Propellant containing 3 ,6-bis(1H- 1, 2, 3, 4-etrazol-5-yl-amino)-1, 2, 4, 5-tetrazine or salts thereof [ P].US 6458227 , 2002.
[79]Yeu-Cherng Lu, Paul H Wierenga. Advanced propellant/ additive development for fire suppressing gas generators[A]. Proceedings of Halon Options Technical Working Conference[C]. 2000: 361-370.
[80]Burns S P. Moquin L A. Nonazide gas generating compositions for airbag inflation with low autoignition temperature[P]. US, 6007647, 1999.
[81]Liu M F, Wang B, Cheng Y. A N-heterocyclic carbine derived highly regioselective ambidengt C-C-S and C-C-N 1,3-dipolar system[J]. Org Comm, 2006: 1215-1217.
[82]Imming P, Kümmell A, Seitz G. Inverse[4+1] cycloadditions of 2-methyl-2,3-dihydro-1,3-benzothiazole-2-ylidene with 1,2,4,5-tetrazines Heterocycles, 1993,35:299-304.
[2]Whittaker A G. Carbon: a new view of its high temperature behavior[J]. Science, 1978, 200 (4343) : 763-767.
[3]Akagi K, N ishiguchi M , Sh irakawa H, et al. One-dimen-sional conjugated carbyne - synthesis and p roperties [M]. Synth, 1987, 17 (123): 557-566.
[4]Kastner J, Kuzmany H, Kavan L, et al. Reductive p reparation of carbine with high yield and in situ Raman scattering study[J]. Macromolecules, 1995, 28: 344-350.
[5]Kijima M, Sakai Y, Shirakawa H. Electrochemical synthesis of carbine catalyzed by nickel complex[J]. Synthesis Met, 1995, 71:1837-1843.
[6]王世华,陈梓云,王茹.碳的线型同素异形体-卡宾研究进展[J].新型炭材料, 1999, 10: 73-79.
[7]Bourissou D, Grerret O, Gabbai P F, et al. Stable carbenes[J]. Chem Rev, 2000,100: 39-91.
[8]Boufatah N,Gellis A, Maldonado J,et al. Efficient microwave-assisted synthesis of new sulfonybenzimidzole-4,7-diones:heterocyclic quinines with potential antitumor activety[J]. Tetrahedron, 2004, 60: 9131-9137.
[9]彭游,陈智勇,刘燕,等.人工沸石:一种微波干法合成2-芳基取代苯并咪唑衍生物的高效催化剂[J].四川大学学报(自然科学版), 2005, 42: 1054-1055.
[10]Lu J, Yang B, Bai Y. Microwave irradiation synthesis of 2-substituted benzimidazoles using PPA as a catalyst under solvent-free condition[J]. Synth. Commun. 2002, 32, 24: 3703-3709.
[11]Lin S, Isome Y, Stewart E, Liu J, et al. Microwave-assisted one step high-throughput synthesis of benzimizole[J]. Tetrahedron Lett, 2006, 47, 17: 2883-2886.
[12]Nadaf R, Siddiqui N S A, Daniel T, et al. Room temperature ionic liquid promoted regioselective synthesis of 2-aryl benzimizoles, benzoxazoles and benzthiazole under ambient conditions[J]. J Mol Catal A: Chem. 2004, 214: 155-160.
[13]Chen C, Chen Y.Liquid-phase synthesis of 2-substituted benzimizoles, benzoxazoles and benzothiazoles[J]. Tetrahedron Lett. 2004, 45: 113-115.
[14]Wang Q, Mao Y, Zhu S. Novel synthesis of 2-per(poly)fluoroalk-1H-benzimidazoles or 2-per(poly)fluoroalkyl benzothiazoles[J]. J. Fluorine Chem.1999, 95: 141-141.
[15]Singh M P, Sasmal S, Lu W Chatterjee M N.Synthetic utility of catalytic Fe(Ⅲ)/Fe(Ⅱ) redox cycling towards fused heterocycles: a facile acess to substituted benzimidazole, bis-benzimidazole and imidazopyridine derivatives[J]. Synthesis, 2000:1380-1390.
[16]Lieu P, Hruno L, Moos H. E.Enantioselective addition of a trefluoromethyl anion to aryl ketones and aldehydes[J]. Synthesis 2003: 1683-1698.
[17]Lurini M, Epifano F, Montanari F,et al. Ytterbium triflate-promoted synthesis of benzimidazole derivatives[J]. Synlett, 2004:1832-1834.
[18]Liu S, Yang L. A simple and efficient procedure for the synthesis of benzimidazoles using air as the oxidant[J]. Tetrahedron Lett. 2005, 46: 4315-4319.
[19]Brain C T, Brunton S A. An intramolecular palladium-catalyzed aryl amination reaction to produce benzimidazole[J]. Tetrahedron Lett. 2002, 43: 1893-1895.
[20]Fonseca T, Gigante B,Gilchrist T.L.A short aynthesis of phenanthro[2,3-d]imdazoles from dehydrobietic acid. Application of the methodology as a convenient route to benzimidazoles[J]. Tetrahedron 2001, 57: 1793-1799.
[21]Harizi A , Zantour H. Ammonium sulfate-magnesium selective reduction of N-2-notrophenylimidates:synthesis of 2-substituted benzimidazoles[J]. Synth. Commun. 2002, 32: 387-392.
[22]刘长令,翟煜翥,张运晓等,防治灰霉病用杀菌剂的开发[J].农药: 2000, 39(3):1-6.
[23]徐扬,王凤山.南瓜胰蛋白酶抑制剂[J].中国新药杂志, 2007, 27(1): 49-51.
[24]李焱,马会强,王玉炉,苯并咪唑及其衍生物合成与应用研究进展[J].有机化学, 2008,28,2: 210-217.
[25]袁勇,周成合,刘嫱,等.新型合成抗菌药物研究进展[J].中国新药杂志, 2-7, 16(5): 343-349.
[26]Andries K, Moeremans M, Gevers T. Substituted benzimidazoles with nanomolar activity against respiratory syncytial vius[J]. Antiviral Res. 2003, 60: 209-219.
[27]宋春泽,周成合,袁勇.磺胺类碳酸酐酶抑制剂研究进展[J].重要新药杂志, 2007, 16(18): 1438-1444.
[28]Migawa M T, Girardet J L, Walker J A. Design, synthesis, and antiviral activity ofα-nucleosides: D-and L-isomers of lyxofuranosyl- and -5-deoxylyxofuranosy benzimidazoles[J]. J.Med. Chem. 1998, 41, 1242-1251.
[29]Porcari A R.,Devivar R V. Kucera, L. S. Design, synthesis, and antiviral evaluations of 1-(substituted benzyl)-2-subsituted-5-6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole. [J]. Med Chem, 1998, 41: 1252-1262.
[30]Biron KK. Antiviral dugs for cytomegalovirus diseases[J]. Anticiral Res, 2006, 71(2-3): 154-163.
[31]高学军,李庆章.苯并咪唑氨基甲酸酯类抗蠕虫药物作用机理研究进展[J].东北农业大学学报, 2004, 35: 492-495.
[32]孟江平,耿荣霞,周成合,苯并咪唑药物研究进展[J],中国新药杂志, 2009, 18, 16: 1505-1514.
[33]毛煜,佘佳红,袁伯俊.苯并咪唑类质子泵抑制剂的药理和临床研究进展[J].中国新药杂志, 2006, 15 (1): 17 - 21.
[34]Labanauskas L K, Brukstus A B, Gaidelis P G. Synthesis and anti-inflammatory activity of some new 1-acyl derivatives of 5,6-diethoxy-2-(methylthio)benzimidazole[J]. Pharm Chem J, 2000, 34, 353-355.
[35] (a) Navarrete V G, Cedillo R, Hernández Campos A.Synthesis and antiparasitic active of 2-(trifluoromethyl)benzimidazole derivatives[J]. Bioorg Med Chem Lett, 2001, 11: 187-190. (b)杨鲁勒,阎世平,白令君.苯并咪唑双铜配合物合成表征和生物活性[J].化学研究与应用, 1995, 7: 28-31.
[36]于克贵,周成合,李东红.大环类药物研究进展[J].中国药学杂志, 2008, 43(7): 481-488.
[37]周晓湘,刘建平.酸洗缓蚀剂的应用研究现状及发展趋势[J].工业水处理, 2002, 22: 16-18, 22.
[38]沈建,余鼎声,庞正智.苯并咪唑化合物作为碳钢缓蚀剂的研究[J].北京化工大学学报, 2005, 32: 110-112.
[39]史志龙,庞正智.新型酮酸酸洗缓蚀剂烷基苯并咪唑的研究[J].北京化工大学学报, 2002, 29: 52-54.
[40]王清华,胡泽祥,娄方等.苯并咪唑的衍生物对润滑油抗磨及抗腐性能的影响[J].润滑与密封, 2001, 26, 22-22: 78-82. (b)王清华,杨官汉.苯并咪唑衍生物抗腐蚀作用机理的研究[J].润滑与密封, 2002, 26: 29-31.
[41]陆伟峰,虞鑫海.聚苯并咪唑树脂的合成及其应用[J].绝缘材料通讯, 2000, 5: 5-9.
[42]Hahn F E, Wittenbecher L, Wan D L et al. Novel 1,2,4-triphosphole, 1,2,3-triphoshetene and azaphospholene derivatives from N-heterocyclic carbenes and phosphaalkynes[J]. Phoshorus, Sulfurand silicon and the Related Elements, 2002,177(6-7): 1863-1867.
[43]蔡志彬,周茂,胡惟笑等.双光气法合成取代苯基异氰酸酯[J].合成化学, 2000(10): 164-166.
[44]俞传明,王亚频,来虎青等.二(-三氯甲基)碳酸酯的应用研究[J].浙江化工, 1998, 29(20): 20-21.
[45]杜晓华,许响声,徐振元.一种安全有效的合成芳基异氰酸酯的方法[J].农药学报, 2002, 12, 4(4): 83-85.
[46]魏文珑,曹桂荣,常宏宏等.固体光气法合成氯代苯基单异氰酸酯[J].应用化学, 2008, 25, 11: 1369-1371.
[47]冯桂荣,张会茹,芳香异氰酸酯的制备方法[J].河北理工学院学报, 2001, 23(4): 66-67.
[48]沈志勇.异氰酸酯合成方法的研析[J] .通化师范学院学, 2004, 25(4): 57-59.
[49]Vrbach Hans.烷基异氰酸酯制备方法[M].农药译丛, 1984,6(1):34-37.
[50]冯桂荣,沈玉龙,劳旺梅.固-液相转移催化法合成对甲基苯异氰酸酯[J].化工进展, 2002, 21(6): 407-409.
[51]Jun H K, Kin J S, No H k, et al. Chitosanasa Co2 agulant for Recovery of Protenaceous Solids From Tofu Wastewater[J]. J Agnc, Food Chem, 1994, 42: 1834-1838.
[52]赵季芝.光气化产品的开发和应用[J].氯碱工业, 1997(12): 35-38.
[53]王长皇.相转移催化技术在农药合成中的应用进展[J],湖北化工, 1991(3): 34-38.
[54] Aguilar E, Meyers A I, Rrinvestigation of a modified Hantzsch thiazole synthesis, Tetrahedron Lett. 1994,35:2473-2476.
[55] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006: 126.
[56] Lobell M, D H G,Grout. Pyruvate decarboxylase: Amolecular modeling study of pyruvate decarboxylation and acyloin formation[J].J Am Chem Soc,1996,118:1867-1872.
[57] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006: 127.
[58] Contant P, Forzy L, Heingartner U, et al. A new convergent synthesis of thiamine hydrochloride[J]. Helv Chim Acta, 1990, 73: 1300-1305.
[59] Ahmed I, Khazi M, Mahajanshetti C S, et al. Synthesis and antimicrobical activity of some 2-(substituted carboxamidomethyl/thyithio)-5-(2-thienyl)-1,3,4-oxadiazole[J]. Indian J Hetercocycli Chem, 2003, 13(1): 87-88.
[60] Kienle M, Dunst C, Knochel P. Oxidative amination of heteroaromatic zinc reagents mediated bu PhI(OAc)2[J]. Org Lett, 2009, 11(22): 5158-5161.
[61] Roush D M, Davis S G, Lutomski K A, et al. Ethynylbenzothiophene pesticides[P]. US 5073564, 1991, 12, 17.
[62] Dekeyser M A, Mcphee D J, Mcdonald P T. Miticidal hydrazine compounds and their intermediates [P]. US 5567723, 1995, 10, 03.
[63]Maienfisch P L, Gsell L, Rindlisbacher A. Synthesis and insecticidal activity of CGA 293, 343-a novel broadspectrum insecticide[J]. Pestic Sci, 1999, 55(3): 351-354.
[64]Maienfisch P L, Huerlimann H, Rindlisbacher A, et al. The discovery of thiamethoxam: a second-generation neonicotinoid [J]. Pest Manag Sci, 2001, 57(2): 165-176.
[65]Uneme H, Iwanaga K, Higuchi N, et al. Synthesis and insecticidal activity of nitroguanidinederivatives[J]. PesticSci, 1999, 55(2): 202-205.
[66]谢心宏,王福久.噻虫啉—一种新的叶面施用杀虫剂[J].农药, 2001, 40(1): 41-42.
[67]Song Y, Kim D S. Fungicidal composition containing n-(α-cyano-2-thenyl) -4-enthyl-2-enthylaylamino-5-thiazole carboxamide(ethaboxam) and as an adjust polyoxyakylene alkye ether [P]. US 2003 020 3949, 2003.
[68]梁芳珍,徐克花,任建成. 2-氨基噻唑缩取代水杨醛Zn(Ⅱ)配合物的合成、表征及抑菌活性[J] .合成化学, 1999,7(2): 121-124.
[69]刘长令.杀虫杀螨剂研究开发的新进展[J].农药,2003, 42(10): 1-4.
[70]Chavez D. 3-3’-Azobis(6-amino-S-tetrazine): A Novel High Nitrogen Energentic Material[J]. Angew Chem, 2000, 39(10): 1791-1793.
[71]Pilgrim K H G,Skiles R D.Tetrazine Herbicid~[P].us 3 860 589,1975.
[72]周茂,蔡志彬,杨忠愚,等.四嗪衍生物的合成及其抗癌性能研究(Ⅰ)-N, N-二苯基-3, 6-二甲基-1, 4-二氢-1, 2, 4, 5-四嗪-1, 4-二甲酰胺[J] .浙江工业大学学报, 1999, 6: 18-21.
[73]饶国武,周欣,杨忠愚,农药四螨嗪合成新工艺[J].农药, 2003, 42, 2:13-14.
[74] Theophil E,李海涛等译,杂环化学[Z],化学工业出版社, 2006:389.
[75]董海山.高能量密度材料的发展及对策[J].含能材料, 2004(增刊), 1-11.
[76]Hiskey M, Chavez D. Insenstitive high nitrogen compounds [R]. NRIS No: DE-2001-776133, 2001.
[77]Hiskey M, Chavez D, et al. Progress in high-nitrogen chemistry in explosives, propellants and pyrotechnics [A]. Proc.27th International Pyrotechnics Seminar [C], July 16～21, USA: Colorado, 2000: 3 - 14.
[78]Hiskey M, Chavez D , et al. Propellant containing 3 ,6-bis(1H- 1, 2, 3, 4-etrazol-5-yl-amino)-1, 2, 4, 5-tetrazine or salts thereof [ P].US 6458227 , 2002.
[79]Yeu-Cherng Lu, Paul H Wierenga. Advanced propellant/ additive development for fire suppressing gas generators[A]. Proceedings of Halon Options Technical Working Conference[C]. 2000: 361-370.
[80]Burns S P. Moquin L A. Nonazide gas generating compositions for airbag inflation with low autoignition temperature[P]. US, 6007647, 1999.
[81]Liu M F, Wang B, Cheng Y. A N-heterocyclic carbine derived highly regioselective ambidengt C-C-S and C-C-N 1,3-dipolar system[J]. Org Comm, 2006: 1215-1217.
[82]Imming P, Kümmell A, Seitz G. Inverse[4+1] cycloadditions of 2-methyl-2,3-dihydro-1,3-benzothiazole-2-ylidene with 1,2,4,5-tetrazines Heterocycles, 1993,35:299-304.