CN103864714A - 一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 - Google Patents
一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 Download PDFInfo
- Publication number
- CN103864714A CN103864714A CN201410075861.6A CN201410075861A CN103864714A CN 103864714 A CN103864714 A CN 103864714A CN 201410075861 A CN201410075861 A CN 201410075861A CN 103864714 A CN103864714 A CN 103864714A
- Authority
- CN
- China
- Prior art keywords
- thiazole
- ethyl formate
- phenyl
- tbhp
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- GNILQILJGXGQDZ-UHFFFAOYSA-N CCOC(c1cnc(-c(c(C(c(cc2)ccc2Br)=O)ccc2)c2C(C(CC2)=CC=C2Br)=O)[s]1)=O Chemical compound CCOC(c1cnc(-c(c(C(c(cc2)ccc2Br)=O)ccc2)c2C(C(CC2)=CC=C2Br)=O)[s]1)=O GNILQILJGXGQDZ-UHFFFAOYSA-N 0.000 description 1
- UDUDWQJIYUHPCL-UHFFFAOYSA-N CCOC(c1cnc(-c(c(C(c(cc2)ccc2F)=O)cc(OC)c2)c2C(c(cc2)ccc2F)=O)[s]1)=O Chemical compound CCOC(c1cnc(-c(c(C(c(cc2)ccc2F)=O)cc(OC)c2)c2C(c(cc2)ccc2F)=O)[s]1)=O UDUDWQJIYUHPCL-UHFFFAOYSA-N 0.000 description 1
- MVSGULNBTGODLO-UHFFFAOYSA-N CCOC(c1cnc(-c(c(C(c(cc2)ccc2F)=O)ccc2)c2C(c(cc2)ccc2F)=O)[s]1)=O Chemical compound CCOC(c1cnc(-c(c(C(c(cc2)ccc2F)=O)ccc2)c2C(c(cc2)ccc2F)=O)[s]1)=O MVSGULNBTGODLO-UHFFFAOYSA-N 0.000 description 1
- MTTRWSXFSDZPHM-UHFFFAOYSA-N CCOC(c1cnc(-c(c(C(c2ccccc2)=O)cc(I)c2)c2C(c2ccccc2)=O)[s]1)=O Chemical compound CCOC(c1cnc(-c(c(C(c2ccccc2)=O)cc(I)c2)c2C(c2ccccc2)=O)[s]1)=O MTTRWSXFSDZPHM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
本发明涉及有机化学领域,具体涉及一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法。以2-苯基噻唑-5-甲酸乙酯衍生物和取代苯甲醛作为底物,以二乙腈氯化钯为催化剂,三苯基膦为配体,三甲基乙酸为添加剂,在TBHP氧化条件下,经自由基机理反应合成得到2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物;本发明合成方法具有收率高,原料易得,反应设备简单,原子经济性高等诸多优点。
Description
技术领域
本发明涉及一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法,属于有机化学合成方法学领域。
背景技术
芳基酮结构是一类重要的合成中间体,易于进一步官能团化,因此在天然产物以及活性化合物的合成中发挥不可替代的作用。传统的Fried-Crafts酰化反应需要化学计量的酰氯试剂,反应条件苛刻且区域选择性差,因此过渡金属催化的醛与芳香化合物的偶联反应已经成为有机合成中构建芳基酮结构的重要方法。
其中钯催化的交叉脱氢偶联反应由于底物均不需要预活化,极大地实现原子经济性。这类反应能通过不同导向基的导向作用来实现邻位的C-H键直接酰基化。目前报道的导向基有吡啶环(Xiaofei Jia.;Shouhui Zhang.;Wenhui Wang.;Fang Luo.;Jiang Cheng.Org.Lett.2009,11,3120),肟醚(Chun-Wo Chan.;Zhongyuan Zhou.;Albert S.C.Chan.;Wing-Yiu Yu.Org.Lett.2010,12,3926),酰基(Yinuo Wu.;Baozhu Li.;Fei Mao.;Xingshu Li.;Fuk Yee Kwong.Org.Lett.2011,13,3258)等。这些方法都只实现导向基邻位的单酰基化反应,且某些反应中导向基的修饰位点有限。现缺乏活性更高、易于修饰或移除的新型导向基,导向双酰基化反应的发生。
本发明以高活性的取代噻唑环作为导向基,其取代基酯链易于修饰或脱除;以2-苯基噻唑-5-甲酸乙酯衍生物和取代苯甲醛作为底物,以二乙腈氯化钯为催化剂,三苯基膦为配体,三甲基乙酸为添加剂,在TBHP氧化条件下,经自由基机理反应合成得到2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物;本发明合成方法具有收率高,原料易得,反应设备简单,原子经济性高等诸多优点。
发明内容
本发明的目的是提供一种合成上述2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的方法;
本发明的目的是通过以下技术方案来实现的,其特征在于通式I所示的:
其中,R1选自氢、卤素、三氟甲基、硝基、甲基或甲氧基;R1优选氢、氯、甲基或甲氧基。R2选自氢、卤素、三氟甲基、甲基或甲氧基;优选氟,氯,溴。
2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法(反应1),包括以下步骤:在反应管中加入2-苯基噻唑-5-甲酸乙酯衍生物和取代苯甲醛,钯催化剂,配体,TBHP(65%水溶液),添加剂和溶剂,加热反应24小时。所述的钯催化剂包括Pd(CH3CN)2Cl2,Pd(OAc)2Pd(TFA)2,PdCl2,Pd(PPh3)2Cl2,优选为Pd(CH3CN)2Cl2;所述的配体选自AsPPh3,Pcy3,dppe,dppf,PPh3P=O,Dave Phos,X-Phos,优选为PPh3;所述的氧化剂选自TBHP,air,Cu(OAc)2·H2O,oxone,BQ,IBX,AgF,AgNO3,Cu(CF3SO2O)2,Ag3PO4,优选为TBHP。所述的添加剂选自PivOH,AcOH,TsOH,NaH2PO4,NaOAc,Et3N,K2CO3,CSF,CSCO3,优选为PivOH;所述的有机溶剂选自氯苯,邻二氯苯,甲苯,二甲苯,NMP,水,DMF,对二甲苯,间二甲苯,优选为邻二氯苯。催化剂2%-10mol%,选用5mol%;配体10mol%、20mol%,选用10mol%;氧化剂2-6equiv.,选用4equiv.;添加剂1-4equiv.,选用2equiv.;有机溶剂优选用2mL;反应温度选自80℃-160℃,优选160℃。
反应1
参照反应1所示:
在反应管中加入2-苯基噻唑-5-甲酸乙酯衍生物和取代苯甲醛,Pd(CH3CN)2Cl2,PPh3配体,TBHP(65%水溶液),PivOH和邻二氯苯,于160℃油浴中加热反应24小时。得到2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物。
具体实施方式
下面结合具体实施例来进一步描述本发明,本发明的优点和特点将会随着描述而更为清楚。但这些实施例仅是范例性的,并不对本发明的范围构成任何限制。本领域技术人员应该理解的是,在不偏离本发明的精神和范围下可以对本发明技术方案的细节和形式进行修改或替换,但这些修改和替换均落入本发明的保护范围内。
实施例1
2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯(1)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品184mg,产率83.4%。
IR(KBr):3481,3416,3134,3098,2360,2331,1711,1671,1587,1449,1399,1294,1097,1004,919,709,677cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.26(t,3H,J=7.1Hz),4.22(q,2H,J=7.1Hz),7.36(t,4H,J=7.4Hz),7.50(t,2H,J=7.4Hz),7.69-7.75(m,7H),8.00(s,1H);13CNMR(75MHz,CDCl3)δ:195.8,167.3,160.3,147.6,140.5,136.1,133.1,131.4,130.1,129.9,129.4,129.2,128.0,61.1,13.7;MS(ESI)m/z442.3[M+H]+.mp:110-111℃.
实施例2
2-(2,6-二对氯苯甲酰苯基)噻唑-5-甲酸乙酯(2)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg, 0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品175mg,产率68.9%
IR(KBr):3418,3134,2987,1724,1668,1657,1585,1571,1401,1309,1265,1253,1092,1006,919,848,751,683cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.29(t,3H,J=7.1Hz),4.25(q,2H,J=7.1Hz),7.32(t,4H,J=12.5Hz),7.69(m,6H),7.75(s,1H),8.00(s,1H);13C NMR(75MHz,CDCl3)δ:195.0,167.2,160.1,148.1,140.6,140.2,134.9,132.3,131.2,130.3,130.0,128.9,128.5,61.8,14.2;MS(ESI)m/z510.2[M+H]+.mp:160-161℃.
实施例3
2-(2,6-二间氯苯甲酰苯基)噻唑-5-甲酸乙酯(3)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色固体产品190mg,产率74.6%。
IR(KBr):3475,3415,3133,2360,2324,1718,1681,1663,1570,1511,1399,1249,1094,765,690,648cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.29(t,3H,J=7.38Hz),4.26(q,2H,J=7.14Hz),7.31(t,3H,J=7.71Hz),7.47(d,2H,J=7.98Hz),7.56(d,2H,J=7.71Hz),7.67-7.76(m,5H),8.02(s,1H);13C NMR(75MHz,CDCl3)δ:194.8,167.3,160.6,148.1,140.4,138.1,134.9,133.5,132.3,130.7,130.6,129.9,129.5,128.1,61.8,14.2;MS(ESI)m/z510.2[M+H]+.mp:102-103℃.
实施例4
2-(2,6-二对氟苯甲酰苯基)噻唑-5-甲酸乙酯(4)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色晶体172mg,产率72.3%。
IR(KBr):3481,3415,3126,2925,2850,1728,1673,1659,1597,1517,1505,1400,1311,1251,1156,1091,1001,853,600cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.29(t,3H,J=7.2Hz),4.25(q,2H,J=7.2Hz),7.04(t,4H,J=8,.58Hz),7.66-7.78(m,7H),8.00(s,1H);13C NMR(75MHz,CDCl3)δ:194.2,167.1,166.9,163.7,160.1,147.6,140.2,132.5,132.5,132.1,132.0,131.6,129.8,129.4,115.4,115.1,61.2,13.6;MS(ESI)m/z478.2[M+H]+.mp:137-138℃.
实施例5
2-(2,6-二对溴苯甲酰苯基)噻唑-5-甲酸乙酯(5)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再 经硅胶柱层析得到白色固体产品136mg,产率45.6%。
IR(KBr):3475,3415,3133,1722,1666,1585,1400,1302,1249,1069,1004,842,748cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.30(t,3H,J=7.02Hz),4.26(q,2H,J=7.02Hz),7.50-7.60(m,8H),7.66-7.72(m,3H),8.01(s,1H);13C NMR(75MHz,CDCl3)δ:194.8,166.7,160.2,147.7,140.0,134.8,131.8,131.4,130.7,129.8,129.4,128.6,61.3,13.7;MS(ESI)m/z598.0[M+H]+.mp:173-174℃.
实施例6
2-(2,6-二苯甲酰-4-甲基苯基)噻唑-5-甲酸乙酯(6)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色固体产品182mg,产率80.2%。
IR(KBr):3422,3128,2925,2855,1715,1676,1662,1590,1511,1400,1249,1092,712,650,518cm-1;1HNMR(CDCl3,300MHz,ppm)δ:1.16(t,3H,J=7.1Hz),4.11(q,2H,J=7.1Hz),7.34(t,4H,J=7.5Hz),7.46-7.51(m,4H),7.72(d,4H,J=7.5Hz),7.95(s,1H);13C NMR(75MHz,CDCl3)δ:196.7,167.9,160.8,148.1,140.9,140.5,136.7,133.5,131.6,130.8,129.8,128.5,127.7,61.6,21.3,14.2;MS(ESI)m/z456.0[M+H]+.mp:119-120℃.
实施例7
2-(2,6-二苯甲酰-4-甲氧基苯基)噻唑-5-甲酸乙酯(7)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色固体产品188mg,产率79.9%。
IR(KBr):3546,3487,3414,1714,1663,1514,1446,1399,1328,1253,1225,1128,1095,1007,709,653,527cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.24(t,3H,J=7.1Hz),3.81(s,3H),4.10(q,2H,J=7.1Hz),7.09(s,2H),7.25(t,4H,J=7.7Hz),7.39(t,2H,J=7.2Hz),7.63(d,4H,J=7.3Hz),7.83(s,1H);13C NMR(75MHz,CDCl3)δ:196.2,167.7,160.8,160.3,148.0,142.5,136.4,133.6,131.3,129.8,128.5,122.6,115.7,61.5,56.0,14.1;MS(ESI)m/z472.2[M+H]+.mp:125-126℃.
实施例8
2-(2,6-二苯甲酰-4-氟苯基)噻唑-5-甲酸乙酯(8)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品146mg,产率63.6%。
IR(KBr):3423,3133,3016,1713,1670,1594,1514,1446,1400,1253,1090,1010,857,709cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.31(t,3H,J=7.1Hz),4.26(q,2H,J=7.1Hz),7.42(t,6H,J=8.0Hz),7.56(t,2H,J=7.4Hz),7.77(d,4H,J=7.4Hz),8.00(s,1H);13C NMR(75MHz,CDCl3)δ:194.4,166.1,163.6,160.2,147.6,142.9,142.8,135.5,133.4,129.4,128.1,117.2,116.9,61.2,13.6;MS(ESI)m/z460.0[M+H]+.mp:111-112℃.
实施例9
2-(2,6-二苯甲酰基4-氯苯基)噻唑-5-甲酸乙酯(9)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品188mg,产率79%。
IR(KBr):3552,3414,3133,3003,2360,1713,1658,1617,1514,1400,1252,1098,1010,712,645cm-1;1HNMR(CDCl3,300MHz,ppm)δ:1.26(t,3H,J=7.1Hz),4.22(q,2H,J=7.1Hz),7.38(t,4H,J=7.7Hz),7.52(t,2H,J=7.4Hz),7.65(s,2H),7.72(d,4H,J=7.2Hz),7.96(s,1H);13C NMR(75MHz,CDCl3)δ:194.9,166.5,160.6,148.1,142.4,136.4,136.1,133.9,132.2,130.1,129.9,128.8,128.7,61.7,14.1;MS(ESI)m/z476.0[M+H]+.mp:143-144℃.
实施例10
2-(2,6-二苯甲酰-4-溴苯基)噻唑-5-甲酸乙酯(10)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品164mg,产率63.1%。
IR(KBr):3398,3129,2991,1712,1680,1664,1590,1514,1448,1399,1312,1250,1146,1098,1009,969, 886,801,710,650,518cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.26(t,3H,J=6.8Hz),4.21(q,2H,J=6.8Hz),7.38(t,4H,J=7.0Hz),7.52(t,2H,J=6.9Hz),7.72(d,4H,J=7.3Hz),7.80(s,2H),7.96(s,1H);13C NMR(75MHz,CDCl3)δ:194.8,166.5,160.6,148.2,142.4,136.1,133.9,132.9,132.2,129.9,129.2,128.7,124.3,61.7,14.2;MS(ESI)m/z520.2[M+H]+.mp:163-164℃.
实施例11
2-(2,6-二苯甲酰-4-碘苯基)噻唑-5-甲酸乙酯(11)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品130mg,产率45.8%。
IR(KBr):3398,3128,2991,2903,1711,1679,1664,1587,1513,1447,1400,1313,1272,1252,1097,1008,969,886,754,709,649cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.26(t,3H,J=7.1Hz),4.21(q,2H,J=7.1Hz),7.37(t,4H,J=7.5Hz),7.52(t,2H,J=7.2Hz),7.71(d,4H,J=7.5Hz),7.97(d,3H,J=10.4Hz);13C NMR(75MHz,CDCl3)δ:194.7,166.7,160.6,148.2,142.2,138.7,136.1,133.9,132.2,129.9,129.7,128.7,95.9,61.7,14.2;MS(ESI)m/z568.0[M+H]+.mp:156-157℃.
实施例12
2-(2,6-二苯甲酰-4-三氟甲基苯基)噻唑-5-甲酸乙酯(12)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(13mg,0.05mmol,0.1eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol, 2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品189mg,产率74.2%。
IR(KBr):3416,3132,2997,2366,2324,1721,1672,1595,1511,1451,1401,1357,1311,1267,1176,1136,1096,1009,913,798,709,650cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.17(t,3H,J=7.1Hz),4.13(q,2H,J=7.1Hz),7.39(t,4H,J=7.5Hz),7.53(t,2H,J=7.4Hz),7.72(d,4H,J=7.3Hz),7.93(s,2H),8.00(s,1H);13C NMR(75MHz,CDCl3)δ:194.9,165.9,160.5,148.3,141.8,135.9,134.1,133.6,132.7,132.1,131.7,129.9,128.7,126.9,126.9,61.8,14.1;MS(ESI)m/z510.0[M+H]+.mp:128-129℃.
实施例13
2-(2,6-二对氟苯甲酰-4-甲基苯基)噻唑-5-甲酸乙酯(13)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色固体产品184mg,产率74.8%。
IR(KBr):3422,3126,2979,2372,1716,1669,1597,1505,1401,1282,1253,1153,1092,848,753,603cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.28(t,3H,J=7.1Hz),2.52(s,3H),4.24(q,2H,J=7.1Hz),7.03(t,4H,J=8.6Hz),7.49(s,2H),7.75(dd,4H,J=5.4Hz,8.8Hz),7.98(s,1H);13C NMR(75MHz,CDCl3)δ:194.5,167.0,163.6,160.2,147.5,140.4,140.1,132.6,132.6,132.0,131.9,131.3,130.3,126.9,115.4,115.1,61.2,20.8,13.6;MS(ESI)m/z492.2[M+H]+.mp:134-135℃.
实施例14
2-(2,6-二间氯苯甲酰-4-甲基苯基)噻唑-5-甲酸乙酯(14)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到白色固体产品184mg,产率70.4%。
IR(KBr):3416,3128,3003,1718,1680,1655,1400,1308,1258,1204,1091,777,721,695cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.29(t,3H,J=7.0Hz),2.53(s,3H),4.25(q,2H,J=7.0Hz),7.29(t,2H,J=7.8Hz),7.50(m,6H),7.73(s,2H),7.99(s,1H,J=7.2Hz);13C NMR(75MHz,CDCl3)δ:194.6,166.8,160.2,147.6,140.4,139.8,137.6,134.3,132.9,131.5,130.6,129.3,128.9,127.6,127.3,61.2,21.9,13.7;MS(ESI)m/z524.0[M+H]+.mp:120-121℃.
实施例15
2-(2,6-二对溴苯甲酰-4-甲基苯基)噻唑-5-甲酸乙酯(15)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色固体产品229mg,产率75.0%。
IR(KBr):3416,3132,3093,2980,1725,1661,1585,1506,1398,1248,1237,1156,1091,1068,1007,861, 836,776,747,661cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.29(t,3H,J=7.1Hz),2.51(s,3H),4.24(q,2H,J=7.1Hz),7.46-7.59(m,10H),7.97(s,1H);13C NMR(75MHz,CDCl3)δ:195.0,166.8,160.2,147.6,140.4,139.9,134.8,131.4,131.0,130.7,130.4,128.4,127.0,61.3,20.9,13.7;MS(ESI)m/z634.0[M+Na]+.mp:129-130℃.
实施例16
2-(2,6-二对氟苯甲酰-4-甲氧基苯基)噻唑-5-甲酸乙酯(16)
取一反应管,加底物0.5mmol和取代苯甲醛(3mmol,6eq),二乙腈氯化钯(6.5mg,0.025mmol,0.05eq),三苯基膦(13mg,0.05mmol,0.1eq),三甲基乙酸(0.115mL,1mmol,2eq),TBHP(65%溶液)(0.3mL,2mmol,4eq),邻二氯苯2mL,在160℃油浴中反应24小时。反应体系冷却至室温,乙酸乙酯稀释,硅藻土过滤除去金属残渣。滤液经饱和NaOH溶液、饱和Na2SO3溶液、饱和食盐水洗涤,无水Na2SO4干燥,减压浓缩得到深色粗品,再经硅胶柱层析得到淡黄色油状产品169mg,产率66.6%。
IR(KBr):3180,3074,2985,2020,2855,1715,1671,1596,1505,1422,1332,1297,1236,1154,1133,1094,1012,850,787,755,602cm-1;1H NMR(CDCl3,300MHz,ppm)δ:1.28(t,3H,J=7.1Hz),3.92(s,3H),4.23(q,2H,J=7.1Hz),7.02(t,4H,J=8.6Hz),7.17(s,2H),7.76(dd,4H,J=5.4Hz,8.7Hz),7.94(s,1H);13C NMR(75MHz,CDCl3)δ:194.6,167.6,167.3,164.2,160.7,160.5,148.0,142.2,132.8,132.8,132.5,132.4,131.5,122.2,115.9,115.6,61.7,56.0,14.1;MS(ESI)m/z508.2[M+H]+。
Claims (8)
2.权利要求1所述的方法,其特征在于所述的钯催化剂包括Pd(CH3CN)2Cl2,Pd(OAc)2,Pd(TFA)2,PdCl2,Pd(PPh3)2Cl2,优选为Pd(CH3CN)2Cl2。
3.权利要求1所述的方法,其特征在于所述的配体选自AsPPh3,Pcy3,dppe,dppf,PPh3P=O,Dave Phos,X-Phos,优选为PPh3。
4.权利要求1所述的方法,其特征在于所述的氧化剂选自TBHP,air,Cu(OAc)2·H2O,oxone,BQ,IBX,,AgF,AgNO3,Cu(CF3SO2O)2,Ag3PO4,优选为TBHP。
5.权利要求1所述的方法,其特征在于所述的添加剂选自PivOH,AcOH,TsOH,NaH2PO4,NaOAc,Et3N,K2CO3,CSF,CSCO3,优选为PivOH。
6.权利要求1所述的方法,其特征在于所述的有机溶剂选自氯苯,邻二氯苯,甲苯,二甲苯,NMP,水,DMF,对二甲苯,间二甲苯,优选为邻二氯苯。
7.权利要求1所述的方法,其特征在于底物2-苯基噻唑-5-甲酸乙酯衍生物投料0.5mmol,其中底物、醛、催化剂、配体、氧化剂、添加剂投料摩尔比为:1∶6∶0.05∶0.1∶4∶2。
8.权利要求1所述的方法,其特征在于反应温度选自80℃-160℃,优选160℃。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410075861.6A CN103864714A (zh) | 2014-03-04 | 2014-03-04 | 一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410075861.6A CN103864714A (zh) | 2014-03-04 | 2014-03-04 | 一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN103864714A true CN103864714A (zh) | 2014-06-18 |
Family
ID=50903784
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410075861.6A Pending CN103864714A (zh) | 2014-03-04 | 2014-03-04 | 一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103864714A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104725174A (zh) * | 2015-02-16 | 2015-06-24 | 湘潭大学 | 一种非金属催化直接合成联芳烃化合物的制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102174028A (zh) * | 2011-03-17 | 2011-09-07 | 中国药科大学 | 一种噻唑-4-甲酸乙酯类衍生物的制备方法 |
-
2014
- 2014-03-04 CN CN201410075861.6A patent/CN103864714A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102174028A (zh) * | 2011-03-17 | 2011-09-07 | 中国药科大学 | 一种噻唑-4-甲酸乙酯类衍生物的制备方法 |
Non-Patent Citations (4)
Title |
---|
ARGHYA BANERJEE ET AL.: "Palladium-Catalyzed ortho-Aroylation of 2-Arylbenzothiazoles and 2-Arylbenzoxazoles with Aldehydes", 《EUR. J. ORG. CHEM.》 * |
FUHONG XIAO ET AL.: "Palladium-Catalyzed Oxidative sp2 C-H Bond Acylation with Alcohols", 《ORGANIC LETTERS》 * |
QIUPING DING ET AL.: "Palladium-catalyzed direct ortho-acylation through an oxidative coupling of 2-arylbenzothiazoles with benzylic alcohols", 《TETRAHEDRON》 * |
QIUPING DING ET AL.: "Pd(II)-catalyzed ortho arylation of 2-arylbenzothiazoles with aryl iodides via benzothiazole-directed CeH activation", 《JOURNAL OF ORGANOMETALLIC CHEMISTRY》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104725174A (zh) * | 2015-02-16 | 2015-06-24 | 湘潭大学 | 一种非金属催化直接合成联芳烃化合物的制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107250102B (zh) | 通过钌催化由偶氮苯制备联苯胺的方法 | |
CN105801575A (zh) | 一种咪唑并[1,2-a]吡啶的合成方法 | |
CN103833672A (zh) | 一种n-丁基-5-苯基噻唑-4-甲酰胺类衍生物的制备方法 | |
CN102070586B (zh) | 一种合成4-位杂原子取代环己烯基卤代物的工艺方法 | |
WO2016086710A1 (zh) | 一种羧酸的制备方法 | |
KR20100101315A (ko) | 트리플루오로아세트산을 이용한 페난트리딘 유도체의 제조방법 | |
CN112442008B (zh) | 一种温度调控单质硫与活泼内炔制备1,4-二噻烯和噻吩类化合物的方法及其转化反应 | |
WO2010122794A1 (ja) | ピラジンカルボン酸誘導体の製造方法及びその中間体 | |
KR101728443B1 (ko) | 2-아미노니코틴산벤질에스테르 유도체의 제조 방법 | |
JP5578809B2 (ja) | 3−メチル−2−チオフェンカルボン酸の製造方法 | |
CN105622302A (zh) | 一种取代连苯三酚的合成方法 | |
CN103864714A (zh) | 一种2-(2,6-二苯甲酰苯基)噻唑-5-甲酸乙酯类衍生物的制备方法 | |
KR20120117831A (ko) | 2-아미노-4-트리플루오로메틸피리딘류의 제조 방법 | |
CN105566260A (zh) | 一种呋塞米的制备方法 | |
CN113200841B (zh) | 一种基于Heck偶联合成消旋萘普生的新工艺 | |
CN110520411A (zh) | 吡啶化合物的制造方法 | |
CN108358866B (zh) | 一种非布司他中间体的制备方法及其在制备非布司他中的应用 | |
CN103755657B (zh) | 一种利伐沙班中间体的制备方法 | |
CN109232316B (zh) | 一类α-三级腈结构β-二羰基化合物的合成方法 | |
CN102791661A (zh) | 二氟环丙烷化合物的制造方法 | |
CN111393364A (zh) | 一种含C(sp2)-S键芳基砜化合物的合成方法 | |
Wang et al. | 2, 2′-Diamino-6, 6′-dimethylbiphenyl as an efficient ligand in the CuI-catalyzed Sonogashira reaction of aryl iodides and bromides with terminal alkynes | |
CN107935909A (zh) | 一种尼达尼布(nintedanib)及其中间体的合成方法 | |
CN104418805B (zh) | 一种达比加群酯中间体及其制备方法和应用 | |
CN105175370A (zh) | 一种2-氟-5-[(3-氧代-1(3h)-异苯并呋喃亚基)甲基]苯腈的合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140618 |