沙坦联苯的高效合成
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摘要
沙坦类药物是临床上备受关注的一类新型抗高血压药物。沙坦联苯是沙坦类药物的关键中间体。以邻氯苯氰和对甲基苯硼酸为原料,通过对反应溶剂、反应温度、反应时间、催化剂、碱等关键条件的优化,开发了一个合成沙坦联苯的催化体系。此催化体系以PEG400为反应介质,以Pd(OAc)_2为催化剂,以K_2CO_3、Na_2CO_3或K_3PO_4为碱,在60℃下反应24 h,沙坦联苯的产率可达99%。该体系是一个绿色、简单、高效合成沙坦联苯的催化体系,为沙坦联苯的合成提供了一个有效的新方法。
Sartan drug is a new type of antihypertensive drug which has been paid much attention in clinic.Sartan biphenyl is a key intermediate for sartan drugs.To develop a new and efficient synthetic method for sartan biphenyl,the effects of solvent,reaction time,catalyst and base on the reaction of o-chlorobenzonitrile and p-tolylboronic acid was investigated.By optimizing above reaction conditions,a green,simple and highly efficient catalytic system for the synthesis of sartan biphenyl was developed. Using PEG400 as solvents and Pd( OAc)_2 as catalysts,sartan biphenyl could be obtained in 99% yield in the presence of K_2 CO_3,Na_2 CO_3 or K_3 PO_4 at 60 ℃ for 24 h.
Sartan drug is a new type of antihypertensive drug which has been paid much attention in clinic.Sartan biphenyl is a key intermediate for sartan drugs.To develop a new and efficient synthetic method for sartan biphenyl,the effects of solvent,reaction time,catalyst and base on the reaction of o-chlorobenzonitrile and p-tolylboronic acid was investigated.By optimizing above reaction conditions,a green,simple and highly efficient catalytic system for the synthesis of sartan biphenyl was developed. Using PEG400 as solvents and Pd( OAc)_2 as catalysts,sartan biphenyl could be obtained in 99% yield in the presence of K_2 CO_3,Na_2 CO_3 or K_3 PO_4 at 60 ℃ for 24 h.
引文
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[19]LIU L,WANG W,XIAO C.A simple and efficient protocol for Suzuki coupling reactions of aryl chlorides and aryl bromides in aqueous DMF[J]. J. Organometal.Chem.,2014,749:83-87.
[20]秦宏宇,刘雷芳.聚乙二醇中氯苯的Suzuki偶联反应研究[J].化学试剂,2014,36(9):781-787.
[2]赵波,张仕禄,罗杰伟,等.醚键桥连的咪唑[1,5-a]吡啶鎓盐的合成及其原位催化Suzuki偶联反应[J].化学试剂,2014,36(11):1 029-1 032.
[3]姜祎,徐虹,莫玲超,等.Suzuki反应合成联苯酚类化合物[J].化学试剂,2017,39(2):211-214.
[4]ZHONG R,POTHIG A,FENG Y,et al. Facile-prepared sulfonated water-soluble PEPPSI-Pd-NHC catalysts for aerobic aqueous Suzuki-Miyaura cross-coupling reactions[J].Green Chem.,2014,16(12):4 955-4 962.
[5]SCHAARSCHMIDT D,LANG H.P,O-Ferrocenes in Suzuki-Miyaura C,C couplings[J]. ACS Catal.,2011,1(4):411-416.
[6]LITTKE A F,DAI C,FU G C.Versatile catalysts for the Suzuki cross-coupling of arylboronic acids with aryl and vinyl halides and triflates under mild conditions[J]. J.Am.Chem.Soc.,2000,122(17):4 020-4 028.
[7]DAI Q,GAO W,LIU D,et al.Triazole-based monophosphine ligands for palladium-catalyzed cross-coupling reactions of aryl chlorides[J].J.Org.Chem.,2006,71(10):3 928-3 934.
[8]SEECHURN C C C J,PARISEL S L,COLACOT T J.Insight into the structure-activity relationship and catalyst activation pathway[J]. J. Org. Chem.,2011,76(19):7 918-7 932.
[9]LIU D,GAO W,DAI Q,et al.Triazole-based monophosphines for Suzuki-Miyaura coupling and amination reactions of aryl chlorides[J].Org.Lett.,2005,7(22):4 907-4 910.
[10]CARROW B P,CHEN L.Tri(1-adamantyl)phosphine:exceptional catalytic effects enabled by the synergy of chemical stability,donicity,and polarizability[J]. Synlett,2017,28:280-288.
[11]亓亮,闻永举,吕美云,等.沙坦联苯的合成研究[J].化学研究与应用,2015,27(1):107-109.
[12]INADA K,MIYAURA N.The cross-coupling reaction of arylboronic acids with chloropyridines and electron-deficient chloroarenes catalyzed by a polymer-bound palladium complex[J]. Tetrahedron,2000,56(44):8 661-8 664.
[13]DEY R,SREEDHAR B,RANU B C. Molecular sievessupported palladium(Ⅱ)catalyst:suzuki coupling of chloroarenes and an easy access to useful intermediates for the synthesis of irbesartan,losartan and boscalid[J].Tetrahedron,2010,66(13):2 301-2 305.
[14]BALEIZAO C,CORMA A,GARCIA H,et al.Oximecarbapalladacycle covalently anchored to high surface area inorganic supports or polymers as heterogeneous green catalysts for the Suzuki reaction in water[J]. J. Org.Chem.,2004,69(2):439-446.
[15]PANDARUS V,DESPLANTIER-GISCARD D,GINGRAS G,et al.Greening the valsartan synthesis:scale-up of key Suzuki-Miyaura coupling over Silia Cat DPP-Pd[J].Org.Process Res.Dev.,2013,17(12):1 492-1 497.
[16]PANDARUS V,GINGRAS G,BELAND F,et al.Process intensification of the Suzuki-Miyaura reaction over solgel entrapped catalyst siliacat DPP-Pd under conditions of continuous flow[J]. Org. Process Res. Dev.,2014,18(11):1 550-1 555.
[17]LIU L,ZHANG Y,WANG Y.Phosphine-free palladium acetate catalyzed Suzuki reaction in water[J]. J. Org.Chem.,2005,70(15):6 122-6 125.
[18]HAN W,LIU C,JIN Z. In situ generation of palladium nanoparticles:a simple and highly active protocol for oxygen-promoted ligand-free Suzuki coupling reaction of aryl chlorides[J].Org.Lett.,2007,9(20):4 005-4 007.
[19]LIU L,WANG W,XIAO C.A simple and efficient protocol for Suzuki coupling reactions of aryl chlorides and aryl bromides in aqueous DMF[J]. J. Organometal.Chem.,2014,749:83-87.
[20]秦宏宇,刘雷芳.聚乙二醇中氯苯的Suzuki偶联反应研究[J].化学试剂,2014,36(9):781-787.