CN114890856A - 一种合成2,2`-联苯基-1-羧酸衍生物的方法 - Google Patents
一种合成2,2`-联苯基-1-羧酸衍生物的方法 Download PDFInfo
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Abstract
本发明属于有机化学的技术领域,公开了一种合成2,2'‑联苯基‑1‑羧酸衍生物的方法。所述方法:在保护性氛围下,以有机溶剂为反应介质,将芳基羧酸与芳基卤化物在钌催化剂,配体和碱性化合物的作用下反应,获得2,2'‑联苯基‑1‑羧酸衍生物。本发明的方法具有产率高、底物适用性广等特点;而且本发明以羧酸和芳基卤化合物为原料,具有原料廉价易制备、操作简便、原子经济性高的优势。本发明方法底物适应性广、催化剂廉价、条件温和,因而有望实际应用于规模生产。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种合成2,2’-联苯基-1-羧酸衍生物的方法。
背景技术
多取代联苯类骨架普遍存在于天然化合物、药物中间体以及功能材料等功能分子中。需要特别指出的是,邻位含有酰胺基取代的2,2’-联苯基-1-羧酸衍生物具有很强的生物活性,例如以下结构的A1~A3化合物。A1化合物可作为FVIIa和TF·FVIIa的抑制剂,FVIIa是一种丝氨酸蛋白酶,可与组织因子(TF)结合,促进细胞凝血(Design,parallelsynthesis,and crystal structures of biphenyl antithrombotics as selectiveinhibitors of tissue factor FVIIa complex.Part 1:Exploration of S2 pocketpharmacophores[J].Bioorg.Med.Chem.,2009,17,3934-3958)。A2化合物作为sTF–FVIIa复合物抑制剂(Probing the S2 site of factor VIIa to generate potent andselective inhibitors:the structure of BCX-3607 in complex with tissue factor–factor VIIa[J].Acta Cryst.,2007.D63,689-697)。A3作为TbGalE的抑制剂,是一种潜在的治疗布鲁氏菌感染的药物(Computer-Aided Identification of Trypanosoma bruceiUridine Diphosphate Galactose 4′-Epimerase Inhibitors:Toward the Developmentof Novel Therapies for African Sleeping Sickness[J].J.Med.Chem.,2010,53,5025-5032)。因此,发展2,2’-联苯基-1-羧酸的合成和结构修饰方法具有重要意义,也引起了化学家的广泛关注。
迄今为止,构建联苯类骨架的方法有很多,例如,过渡金属交叉偶联、过渡金属导向C-H键的芳基化、脱氢交叉偶联、乌尔曼反应等。但制备2’-取代的2,2’-联苯基-1-羧酸的骨架仍十分有限。传统的方法使用芳基卤与邻取代的芳基硼酸、芳基锡、芳基锌等在钯催化或镍催化下可以构建。但以上方法使用的官能化的金属试剂价格昂贵,商业化程度低。尽管羧酸导向C-H的氧化偶联可以合成2’-取代的2,2’-联苯基-1-羧酸,但局限于自偶联或富电子羧酸与贫电子羧酸的交叉偶联(Rhodium(I)-Catalyzed Regiospecific Dimerizationof Aromatic Acids:Two Direct C-H Bond Activations in Water[J].Angew.Chem.Int.Ed.,2015,54,5718-5721;Ruthenium(II)Catalysis/NoncovalentInteraction Synergy for Cross-Dehydrogenative Coupling of Arene CarboxylicAcids[J].ACS Catal.,2018,8,10173-10179)。
因此,发展一种由原料廉价易得、底物适用范围广的2’-取代的2,2’-联苯基-1-羧酸衍生物的合成方法显得尤为重要。
发明内容
针对现有技术存在的问题和不足之处,本发明的目的在于提供一种简单且高效的合成2’-取代的2,2’-联苯基-1-羧酸衍生物的方法。本发明使用种类丰富且廉价易得的羧酸和芳基卤为原料,二价钌络合物作为催化剂,膦化合物或菲罗啉作为配体,碳酸钾作为碱,在有机溶剂中,实现羧酸与芳基卤的C-H芳基化反应,以高收率获得2’-取代的2,2’-联苯基-1-羧酸化合物。本发明的方法具有价格低廉,底物适用性广泛,合成的产物具有潜在的药物价值等优点。
本发明通过以下技术方案实现:
一种2’-取代的2,2’-联苯基-1-羧酸衍生物的合成方法,包括如下步骤:在保护性氛围下,以有机溶剂为反应介质,将芳基羧酸与芳基卤化物在钌催化剂,配体和碱性化合物的作用下反应,获得2,2’-联苯基-1-羧酸衍生物。所述碱性化合物为碳酸钾。
反应完后进行后续处理;所述后续处理是指冷却,加入稀酸至体系的pH=0.5~1.5,萃取,去除有机相中溶剂、分离纯化。
其中R1为甲基、甲氧基、苯基、氢;
R2为氢、甲基、氟、氯、甲氧基或三氟甲基;
R3为氢、甲基、甲氧基、甲硫基(CH3-S-)、N,N-二甲基、氟、氯或碘;
X为碘或溴;
R4为氢,烷基,甲氧基,卤素,三氟甲基,甲氧基,甲硫基,N,N-二甲基,乙酰氧基(CH3COO-),苯基,萘基,氰基,乙酰基,烯基,萘基,氨基;
所述烷基优选为C1~3烷基,如:甲基、乙基、异丙基。
所述卤素优选为氟,氯,溴或碘。
R5为氢,新戊酰胺基(叔丁基甲酰胺基),N-正丁基甲酰胺基(C4H9-NH-(C=O)-),N-(4-氟苯基)甲酰胺基、N-(3-腈基苯基)甲酰胺基、N-(3,4-二氯苯基)甲酰胺基,N-(2-溴-3-甲基苯基)甲酰胺基、N-异丙基甲酰胺基,N-叔丁基甲酰胺基、N-苄基甲酰胺基、N-苯基甲酰胺基、甲酰胺基、N,N-二甲基甲酰胺基、对氟苯基甲酰胺基、对氰基苯基甲酰胺基、酯基(CH3OCO-)、乙酮基、甲酰苯丙氨酸甲酯N-(4-甲基-2-氧代-2H-苯并吡喃-7-基)甲酰胺基
R4与R5不同时为氢;
R6为氢、甲基、MeO-C=O-、异丙基;R7为氢、酯基(CH3OCO-)、碘、氟;
R4与R5的基团可以相互替换。
R8为丁基或苯基;R9为CH3O或CH3
所述钌催化剂为二碘(对伞花烃)钌(II)二聚体或二氯(对伞花烃)钌(II)二聚体。
所述配体为三-环己基膦,三-甲基膦,三-丁基膦,三-辛基膦,二苯基甲基膦,三苯基膦,甘氨酸,N-Boc-L-缬氨酸,L-叔亮氨酸,L-脯氨酸,二金刚烷基正丁基膦,二-环己基-苯基膦,[1,1’-联苯]-2-基二-环己基膦,三(4-甲氧基苯基)膦,三呋喃基膦,哌啶-2-羧酸,5-(三氟甲基)吡啶-2-醇,联吡啶,4,4-二甲氧基联吡啶,4,4-二叔丁基联吡啶,菲罗啉,5H-环戊[2,1-b:3,4-b’]联吡啶-5-酮,1,10-菲罗啉-5,6-二酮,2,9-二甲基-菲罗啉,3,4,7,8-四甲基-1,2-菲罗啉,4,7-二苯基菲罗啉,4,7-二甲氧基-菲罗啉,(E)-N-苄基-1-(吡啶-2-基)甲苯胺,2E,3E)-N2,N3-二苯基丁烷-2,3-二亚胺,(2E,3E)-N2,N3-二异丙基丁烷-2,3-二亚胺,(2E,3E)-N2,N3双(2,6-二异丙基苯基)丁烷-2,3-二亚胺,N-苄基吡啶酰胺,N-(2-羟乙基)吡啶酰胺,N、N’-(乙烷-1,2-二酰基)二苯磺酰胺,[2,2’-联吡啶]-6,6’-二醇。
所述配体优选为三-辛基膦或3,4,7,8-四甲基菲罗啉中一种以上。
所述反应的温度为100~120℃,反应的时间为20~26小时。
所述芳基羧酸与芳基卤化合物的摩尔比为1:1.5~2。所述钌催化剂与芳基羧酸的摩尔比为(0.025~0.05):1。所述配体与芳基羧酸的摩尔比为(0.05~0.10):1。
所述有机溶剂为N-甲基吡咯烷酮或N,N-二甲基甲酰胺中一种以上。所述保护性氛围为氮气。
所述后续处理是指调节体系的pH=0.5~1.5,乙酸乙酯萃取,旋去除有机相中溶剂,柱层析分离。所述去除有机相中溶剂是指去除有机相中水,去除有机溶剂。此时后续处理为第一种后续处理方式。
所述去除有机相中水是指采用干燥剂进行干燥,干燥剂为无水硫酸镁,然后过滤;所述去除有机相中有机溶剂是指减压蒸馏去除有机溶剂。
所述柱层析的洗脱液为石油醚和乙酸乙酯的混合溶剂(石油醚与乙酸乙酯的体积比为(3~6):1),或者石油醚、乙酸乙酯和甲酸的混合溶剂,石油醚和乙酸乙酯和甲酸的体积比80:20:1-80:40:1。
为了提高羧酸衍生物的分离提纯效率,将上述反应得到的羧酸化合物进行甲基化,然后进行后续处理(此时的后续处理为第二种后续处理方式。)。所述羧酸化合物为2,2’-联苯基-1-羧酸。所述甲基化是指将羧酸化合物中羧基进行甲基化;所述甲基化是指将羧酸化合物与碘甲烷在碱性化合物的作用下进行反应。
具体地,所述2’-取代的2,2’-联苯基-1-羧酸衍生物的合成方法,包括如下步骤:在保护性氛围下,以有机溶剂为反应介质,将芳基羧酸与芳基卤化物在钌催化剂,配体和碱性化合物的作用下反应,然后进行甲基化,后续处理,获得2,2’-联苯基-1-羧酸衍生物。
此处的后续处理是指淬灭反应、萃取、去除有机相中溶剂、分离纯化。所述后续处理是指淬灭反应,乙酸乙酯萃取,旋去除有机相中溶剂,柱层析分离。所述去除有机相中溶剂是指去除有机相中水,去除有机溶剂。
所述淬灭反应是指向反应体系中加入饱和碳酸氢钠溶液;所述去除有机相中水是指采用干燥剂进行干燥,干燥剂为无水硫酸镁,然后过滤;所述去除有机相中有机溶剂是指减压蒸馏去除有机溶剂。
所述柱层析的洗脱液为石油醚和乙酸乙酯的混合溶剂(石油醚与乙酸乙酯的体积比为(3~6):1),或者石油醚、乙酸乙酯和甲酸的混合溶剂,石油醚和乙酸乙酯和甲酸的体积比80:20:1-80:40:1。
此时2,2’-联苯基-1-羧酸衍生物中1-羧酸为1-羧酸甲酯;羧基被甲基化后,可以通过去除甲基,恢复羧基。
一些2,2’-联苯基-1-羧酸(如:实施例18、19、21、28、35、65)采用第一种后续处理方式具有较高的分离提纯效率;一些2,2’-联苯基-1-羧酸采用第一种后续处理方式分离提纯效率较低,此时需要进行甲基化,采用第二种后续处理方式,提高分离提纯效率。
本发明的2’-取代的2,2’-联苯基-1-羧酸衍生物也可以称为2’-取代的2,2’-联芳基-1-羧酸衍生物。
本发明的合成方法的化学反应方程式:
本发明的合成方法具有如下优点及有益效果:
(1)本发明的方法以金属钌为催化剂,膦化合物或氮化合物为配体,具有产率高、底物适用性广等特点;而且本发明以羧酸和芳基卤化合物为原料,具有原料廉价易制备、操作简便、原子经济性高的优势。
(2)本发明合成方法底物适应性广、催化剂廉价、条件温和,因而有望实际应用于规模生产。
附图说明
图1为实施例1所得目标产物的氢谱图;
图2为实施例11所得目标产物的氢谱图;
图3为实施例19所得目标产物的氢谱图;
图4为实施例21所得目标产物的氢谱图;
图5为实施例24所得目标产物的氢谱图;
图6为实施例65所得目标产物的氢谱图。
具体实施方式
下面结合实施例对本发明作进一步详细的描述,但本发明的实施方式不限于此。
实施例1
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-乙基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率90%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.40-7.33(m,3H),7.28(d,J=8.0,1H),7.23(dt,J=12.0,8.0,2H),7.17(d,J=8.0,1H),3.53(s,3H),2.61(dt,J=20.0,4.0,2H),2.50(s,3H),1.19(t,J=8.0,3H).
13C NMR(100MHz,CDCl3)δ169.4,141.7,139.6,139.4,134.9,133.8,129.2,128.7,128.6,127.8,127.5,127.2,124.7,51.1,25.9,19.5,14.9.
根据以上数据推断所得产物的结构:
实施例2
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-甲基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率89%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.36(t,J=8.0,1H),7.25(t,J=4.0,3H),7.22–7.17(m,1H),7.14(d,J=8.0,1H),7.10(d,J=8.0,1H),3.50(s,3H),2.44(s,3H),2.17(s,3H).
13C NMR(100MHz,CDCl3)δ169.7,140.1,139.9,135.9,135.2,133.7,129.7,129.1,128.9,128.9,127.5,127.1,125.0,51.5,20.0,19.7.
根据以上数据推断所得产物的结构:
实施例3
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2,3-二甲基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率73%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.31(t,J=10.0,1H),7.19(d,J=5.0,1H),7.11(d,J=5.0,1H),7.05(t,J=10.0,2H),6.96(d,J=10.0,1H),3.46(s,3H),2.39(s,3H),2.31(s,3H),2.01(s,3H).
13C NMR(125MHz,CDCl3)δ169.8,140.6,140.2,136.6,135.0,134.5,133.8,129.0,128.9,128.7,127.4,127.0,124.6,51.5,20.5,19.7,16.8.
根据以上数据推断所得产物的结构:
实施例4
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔3-碘-4-甲基苯甲酸甲酯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率75%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.91(dd,J=8.0,2.0,1H),7.81(d,J=1.6,1H),7.35(t,J=7.6,1H),7.30(d,J=8.0,1H),7.24(d,J=7.6,1H),7.04(d,J=8.0,1H),3.88(s,3H),3.47(s,3H),2.41(s,3H),2.18(s,3H).
13C NMR(125MHz,CDCl3)δ169.4,167.0,141.9,140.5,139.0,135.6,133.6,130.3,129.8,129.4,129.2,128.8,127.2,127.1,51.9,51.6,20.3,19.8.
根据以上数据推断所得产物的结构:
实施例5
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-异丙基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率48%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.41–7.32(m,3H),7.25(d,J=7.6,1H),7.17(td,J=12.8,1.6,1H),7.10(d,J=7.6,2H),3.49(s,3H),2.87(dt,J=20.4,6.8,1H),2.44(s,3H),1.18(dd,J=6.8,1.2,6H).
13C NMR(100MHz,CDCl3)δ169.6,146.7,139.9,138.9,135.2,133.9,129.3,128.8,128.7,127.9,127.4,125.2,124.7,51.4,29.9,24.7,23.2,19.8.
根据以上数据推断所得产物的结构:
实施例6
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-甲氧基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率85%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.41–7.31(m,2H),7.23(t,J=6.4,3H),7.02(td,J=8.0,0.8,1H),6.96(d,J=8.2,1H),3.77(s,3H),3.57(s,3H),2.47(s,3H).
13C NMR(100MHz,CDCl3)δ169.6,156.2,137.3,135.7,133.3,130.5,130.0,129.3,129.3,128.8,128.4,120.4,110.5,55.3,51.4,20.2.
根据以上数据推断所得产物的结构:
实施例7
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-硫甲基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率61%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.37(t,J=7.6,1H),7.32(dt,J=10.8,6.0,2H),7.27(d,J=7.6,1H),7.23(d,J=7.6,1H),7.20–7.13(m,2H),3.53(s,3H),2.46(s,3H),2.39(s,3H);
13C NMR(100MHz,CDCl3)δ169.3,139.3,138.5,137.4,135.7,133.3,129.6,129.3,128.9,128.0,127.8,125.3,124.2,51.5,19.9,15.9;
根据以上数据推断所得产物的结构:
实施例8
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N,N-二甲基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率28%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.33(t,J=7.6,1H),7.25(dd,J=8.0,6.2,2H),7.17(d,J=7.0,1H),7.11(dd,J=7.5,1.5,1H),6.96(m,2H),3.55(s,3H),2.50(s,6H),2.42(s,3H).
13C NMR(125MHz,CDCl3)δ169.6,151.0,140.4,136.2,133.6,132.4,130.9,129.6,128.9,128.3,127.9,121.1,117.3,51.3,43.0,20.3
实施例9
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-甲氧基-5-氯-碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率81%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.34(t,J=7.7,1H),7.24(dd,J=8.7,2.6,1H),7.21(d,J=7.6,1H),7.18(d,J=2.6,1H),7.13(d,J=7.6,1H),6.82(d,J=8.7,1H),3.70(s,3H),3.58(s,3H),2.42(s,3H).
13C NMR(125MHz,CDCl3)δ169.2,154.9,136.0,133.1,131.7,130.2,129.9,129.5,128.3,128.2,125.3,111.6,55.6,51.3,20.2.
根据以上数据推断所得产物的结构:
实施例10
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-氧乙酰基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率76%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.97(d,J=7.8,1H),7.51(dt,J=7.5,3.8,1H),7.42(t,J=7.2,1H),7.35(t,J=7.6,1H),7.25(dd,J=14.6,7.6,2H),7.10(d,J=7.6,1H),3.67(s,3H),3.49(s,3H),2.42(s,3H).
13C NMR(100MHz,CDCl3)δ169.3,167.5,141.7,140.2,135.1,132.4,131.2,130.7,130.0,129.9,129.1,128.8,127.4,126.7,51.8,51.5,19.9.
根据以上数据推断所得产物的结构:
实施例11
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-苯基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率52%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.53–7.42(m,2H),7.39(td,J=8.8,1.6,1H),7.35–7.30(m,3H),7.25(m,3H),7.09(dt,J=21,6,7.4,2H),6.76(d,J=7.2,1H),3.62(s,3H),2.45(s,3H).
13C NMR(100MHz,CDCl3)δ169.9,141.1,140.6,140.0,139.3,135.4,133.8,130.2,129.8,129.6,128.7,128.6,127.7,127.7,126.8,126.4,51.6,19.9.
根据以上数据推断所得产物的结构:
实施例12
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-氰基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率59%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.75(d,J=7.2,1H),7.58(td,J=7.7,1.0,1H),7.43(dd,J=15.6,7.8,2H),7.34(dd,J=14.0,7.6,2H),7.25(d,J=7.6,1H),3.53(s,3H),2.45(s,3H).
13C NMR(100MHz,CDCl3)δ168.9,144.6,136.7,136.4,133.0,132.9,132.0,130.8,129.6,129.5,127.7,127.3,117.9,112.3,51.7,19.9.
根据以上数据推断所得产物的结构:
实施例13
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘苯甲酸甲酯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率73%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.86(dd,J=7.5,1.0,1H),7.41(td,J=7.5,1.0,1H),7.32(td,J=7.5,1.0,1H),7.25(t,J=7.5,1H),7.20–7.11(m,2H),6.99(d,J=8.0,1H),3.56(s,3H),3.39(s,3H),2.32(s,3H).
13C NMR(125MHz,CDCl3)δ169.4,167.5,141.7,140.2,135.1,132.4,131.2,130.7,130.0,129.9,129.1,128.9,127.4,126.7,51.8,51.5,19.9.
实施例14
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-(2-碘苯基)新戊酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率64%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ8.12(d,J=8.2,1H),7.41–7.31(m,3H),7.29(d,J=7.5,1H),7.16–7.07(m,3H),3.51(s,3H),2.41(s,3H),1.04(s,9H).
13C NMR(125MHz,CDCl3)δ176.3,169.4,135.9,135.5,135.4,134.2,131.5,129.9,129.7,129.2,128.6,127.4,123.8,122.0,51.89,39.4,27.1,19.6.
根据以上数据推断所得产物的结构:
实施例15
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-乙烯基溴苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率40%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.63(d,J=7.8,1H),7.32(td,J=7.5,3.0,2H),7.24(dd,J=12.5,5.5,2H),7.15(d,J=7.6,1H),7.06(d,J=7.5,1H),6.53(dd,J=17.5,11.0,1H),5.66(d,J=17.5,1H),5.13(d,J=11.0,1H),3.46(s,3H),2.42(s,3H).
13C NMR(125MHz,CDCl3)δ169.6,139.3,139.1,135.9,135.5,135.2,133.8,129.6,129.2,128.9,128.1,127.7,127.1,124.8,114.5,51.6,19.9.
根据以上数据推断所得产物的结构:
实施例16
在氮气保护下,向反应容器中依次加入0.6毫摩尔邻甲基苯甲酸,0.3毫摩尔1,2-二碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率40%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.30–7.24(m,4H),6.99(m,6H),3.59(s,6H),2.38(s,6H).
13C NMR(125MHz,CDCl3)δ170.2,139.5,139.3,134.9,133.7,129.5,128.5,128.5,128.3,127.0,51.6,19.8.
根据以上数据推断所得产物的结构:
实施例17
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔3-碘-2-甲氧基吡啶,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率58%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.36–7.30(m,2H),7.30–7.26(m,1H),7.19(d,J=7.5,2H),6.18(t,J=6.8,1H),3.71(s,3H),3.54(s,3H),2.43(s,3H);
13C NMR(125MHz,CDCl3)δ169.4,161.5,137.6,137.6,136.1,135.9,132.6,132.2,130.0,129.5,127.9,105.4,51.6,37.9,20.4.
根据以上数据推断所得产物的结构:
实施例18
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-丁基-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸水洗酸化、乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率90%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.33(d,J=7.5,1H),7.24(m,2H),7.15–7.09(m,2H),7.05(d,J=7.5,2H),6.70(m,1H),3.11(m,1H),2.99(td,J=12.5,6.5,1H),2.31(s,3H),1.19–1.08(m,2H),1.06–0.95(m,2H),0.70(t,J=7.3,3H).
13C NMR(125MHz,CDCl3)δ171.3,171.2,138.8,137.5,134.8,134.7,134.2,130.0,129.9,129.8,128.7,128.0,126.8,126.2,39.7,30.8,19.7,19.7,13.5.
根据以上数据推断所得产物的结构:
实施例19
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-丁基-2,5-二碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸水洗酸化、乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率62%。
所得产物的结构表征数据如下:
1H NMR(400MHz,DMSO)δ7.87(t,J=5.2,1H),7.85–7.78(m,2H),7.32(m,2H),6.97(d,J=8.0,1H),6.93(dd,J=5.2,3.2,1H),2.99(s,2H),2.36(s,3H),1.09(m,2H),0.97(m,2H),0.73(t,J=7.2,3H).
13C NMR(100MHz,DMSO)δ170.8,167.5,138.9,138.3,138.1,137.1,136.2,134.7,134.5,132.0,130.1,129.2,126.9,94.3,39.1,31.1,19.8,19.7,14.1.
根据以上数据推断所得产物的结构:
实施例20
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-(4-氟苯基)-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率81%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.51(s,1H),7.77(d,J=7.3,1H),7.48–7.41(m,2H),7.25(td,J=7.6,1.1,1H),7.17(dd,J=11.8,5.0,4H),7.08(d,J=7.5,1H),6.87(dd,J=12.5,4.7,2H),3.71(s,3H),2.42(s,3H).
13C NMR(125MHz,CDCl3)δ171.1,167.1,160.0,158.1,138.9,137.7,136.6,135.1,134.2,134.14,132.2,129.9,129.8(d,J=7.5Hz),129.1,128.6,128.2,127.2,121.1(d,J=7.5Hz),115.3,115.1,52.3,19.6.
根据以上数据推断所得产物的结构:
实施例21
在氮气保护下,向反应容器中依次加入0.3毫摩尔苯甲酸,0.45毫摩尔N-(3-氰基苯基)-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液加入稀盐酸酸化直到PH=1~2,加入乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率62%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.00(s,1H),7.85(d,J=7.6,1H),7.74–7.68(m,1H),7.44(d,J=7.2,3H),7.41(d,J=4.8,2H),7.39(d,J=7.6,1H),7.34(d,J=8.5,2H),7.19(d,J=7.3,1H),7.14–7.09(m,1H).
13C NMR(125MHz,CDCl3)δ172.4,168.5,141.8,140.7,138.9,135.2,133.1,132.2,130.8,130.5,129.8,129.6,129.5,128.2,128.1,128.1,119.4,118.7,106.9.
根据以上数据推断所得产物的结构:
实施例22
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-(3,4-二氯苯基)-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三-辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率79%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.74(s,1H),7.75–7.72(m,1H),7.53(d,J=2.4,1H),7.44(m,2H),7.25(t,J=7.7,1H),7.20–7.14(m,3H),7.05–7.01(m,2H),3.74(s,3H),2.42(s,3H).
13C NMR(125MHz,CDCl3)δ171.5,167.3,138.6,137.7,136.3,135.1,132.3,132.1,130.1,130.0,129.9,129.1,128.6,128.3,127.1,126.8,120.8,118.4,52.4,19.5.
根据以上数据推断所得产物的结构:
实施例23
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-(2-溴-3-甲基苯基)-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率27%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.04(s,1H),7.89(d,J=8.1,1H),7.81(dd,J=4.4,2.1,1H),7.47–7.44(m,2H),7.29(d,J=7.9,1H),7.19(d,J=7.2,3H),7.13(t,J=7.8,1H),6.94(d,J=7.3,1H),3.58(s,3H),2.41(s,3H),2.30(s,3H).
13C NMR(125MHz,CDCl3)δ169.6,167.6,138.8,138.3,136.3,136.0,135.9,132.9,130.1,130.0,129.8,129.4,129.0,128.0,127.4,127.1,126.4,120.6,117.0,51.9,23.7,19.9.
根据以上数据推断所得产物的结构:
实施例24
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗、乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率88%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ7.44(d,J=7.4,1H),7.35(t,J=7.6,1H),7.29(d,J=7.6,1H),7.26-7.21(m,2H),7.02(d,J=7.5,1H),6.95(s,1H),3.67(s,3H),3.25-3.16(m,1H),2.93–2.85(m,1H),2.40(s,3H),1.99(s,3H),1.00–0.93(m,4H),0.74(t,J=6.6,3H).
13C NMR(100MHz,CDCl3)δ171.0,169.5,138.0,137.9,136.2,136.0,134.9,133.0,130.8,130.3,129.5,127.9,127.0,125.4,52.2,39.0,31.1,19.9,19.8,19.7,13.7.
根据以上数据推断所得产物的结构:
实施例25
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-N-异丙基-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化,乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率54%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.31(d,J=7.3,1H),7.29-7.27(m,1H),7.26(s,1H),7.23(d,J=7.6,2H),6.74(dd,J=7.5,1.5,1H),6.29(d,J=7.5,1H),4.02-3.91(m,1H),2.44(s,3H),2.00(s,3H),1.13(d,J=6.6,3H),0.99(d,J=6.5,3H).
NMR(125MHz,CDCl3)δ171.5,170.5,138.3,138.1,135.5,135.4,135.0,134.9,132.4,130.0,129.1,128.1,125.2,123.3,42.4,22.2,22.1,19.8,19.7.
根据以上数据推断所得产物的结构:
实施例26
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-N-叔丁基-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化,乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率71%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.28(m,2H),7.25–7.20(m,3H),6.77(d,J=6.5,1H),6.25(s,1H),2.43(s,3H),2.00(s,3H),1.21(s,9H).
13C NMR(125MHz,CDCl3)δ172.0,170.7,138.0,137.8,135.9,135.5,135.4,134.8,132.0,129.8,129.0,128.0,125.3,123.1,52.5,28.2,19.8,19.7.
根据以上数据推断所得产物的结构:
实施例27
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-N-苄基-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率73%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.48(d,J=7.6,1H),7.36(s,1H),7.34–7.27(m,2H),7.23(d,J=7.6,1H),7.19–7.11(m,4H),7.01(d,J=7.5,1H),6.74(d,J=7.0,2H),4.48(dd,J=14.6,7.0,1H),4.04(dd,J=14.6,3.9,1H),3.57(s,3H),2.21(s,3H),1.95(s,3H).
13C NMR(125MHz,CDCl3)δ170.8,169.4,137.8,137.6,137.4,136.3,136.2,135.2,132.7,131.0,130.3,129.6,128.2,127.9,127.5,126.8,126.81,125.6,52.0,43.6,19.9,19.7.
根据以上数据推断所得产物的结构:
实施例28
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-N-苯基-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,将反应液用稀盐酸酸化,乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率95%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ8.29(d,J=13.7,1H),7.46(d,J=7.3,1H),7.44–7.38(m,3H),7.32(m,3H),7.27–7.20(m,2H),7.16(t,J=7.2,1H),6.82(d,J=6.9,1H),2.47(s,3H),2.04(s,3H).
13C NMR(125MHz,CDCl3)δ171.5,170.3,137.9,137.9,137.1,136.0,135.2,134.9,134.4,132.5,130.0,129.7,128.8,128.0,125.7,125.0,124.4,120.6,19.8,19.7;
根据以上数据推断所得产物的结构:
实施例29
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,合并有机相,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率65%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.50(d,J=7.3,1H),7.37(t,J=7.6,1H),7.31(t,J=7.5,1H),7.26(m,2H),7.02(d,J=7.5,1H),6.84(s,1H),5.43(s,1H),3.64(s,3H),2.40(s,3H),1.99(s,3H).
13C NMR(125MHz,CDCl3)δ171.8,170.8,137.9,136.6,136.5,136.3,135.2,132.9,131.4,130.4,129.7,128.0,127.0,125.7,52.1,20.0,19.8.
根据以上数据推断所得产物的结构:
实施例30
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔N-丁基-2-碘-3-甲氧基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,将反应液用稀盐酸酸化,乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏蒸去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率46%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.36(t,J=8.0,1H),7.29–7.25(m,1H),7.24(d,J=5.3,1H),7.05–6.99(m,2H),6.81(d,J=7.0,1H),6.40(s,1H),3.69(s,3H),3.20(td,J=7.2,1.6,2H),2.45(s,3H),1.34(m,2H),1.21(m,2H),0.84(t,J=7.3,3H).
13C NMR(125MHz,CDCl3)δ171.4,170.3,157.6,136.4,135.7,134.9,133.0,130.1,129.7,129.0,127.9,126.2,118.0,113.7,56.2,39.9,31.1,19.9,19.8,13.6.
根据以上数据推断所得产物的结构:
实施例31
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔3-氟-2-碘-N-苯基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,将反应液用稀盐酸酸化,乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率72%。
所得产物的结构表征数据如下:
1H NMR(400MHz,DMSO)δ9.94(s,1H),7.57(m,1H),7.51(d,J=7.5,1H),7.43(t,J=8.6,1H),7.40-7.33(m,3H),7.31–7.23(m,3H),7.11–7.02(m,2H),2.41(s,3H).
13C NMR(125MHz,DMSO)δ171.2,166.0,160.4,158.4,139.3,138.9,135.1,134.9,131.6,130.9,130.5(d,J=8.4Hz),129.8,129.2,127.9,126.6(d,J=19Hz),124.3(d,J=15Hz),119.7,117.4(d,J=23Hz),20.2.根据以上数据推断所得产物的结构:
实施例32
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔3-氯-2-碘-N-苯基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率41%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.07(s,1H),7.64(d,J=7.6,1H),7.50(d,J=8.0,1H),7.39(t,J=7.8,1H),7.32(t,J=7.6,1H),7.22(t,J=8.5,3H),7.19–7.16(m,2H),7.04(d,J=7.6,1H),7.00(t,J=7.2,1H),3.83(s,3H),2.43(s,3H).
13C NMR(125MHz,CDCl3)δ171.5,166.3,139.6,138.0,136.3,136.2,135.6,133.3,132.3,130.8,130.7,129.4,128.7,127.3,126.9,124.0,119.5,52.6,20.1.
根据以上数据推断所得产物的结构:
实施例33
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔正丁基-1-碘-2-萘酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率62%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.88(d,J=8.5,1H),7.83(d,J=8.2,1H),7.70(d,J=8.5,1H),7.49–7.44(m,1H),7.43–7.38(m,1H),7.36(t,J=4.3,2H),7.33(d,J=7.7,1H),7.15(t,J=6.5,1H),7.07(s,1H),3.35(s,3H),3.25-3.32(m,1H),2.98–2.89(m,1H),2.45(s,3H),1.02-0.95(m,4H),0.75(t,J=6.9,3H).
13C NMR(125MHz,CDCl3)δ170.8,169.5,136.8,134.8,134.2,133.6,133.5,131.3,130.3,129.9,128.3,128.1,127.8,126.5,126.4,126.3,124.8,51.9,39.0,31.1,19.8,19.7,13.6.
根据以上数据推断所得产物的结构:
实施例34
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔1-碘代-N-苯基-2-萘酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率68%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.08(s,1H),7.95(t,J=8.9,1H),7.88(d,J=8.2,1H),7.82–7.79(m,1H),7.53–7.48(m,1H),7.40(t,J=4.6,2H),7.36(t,J=5.6,1H),7.30(t,J=7.2,2H),7.25(s,1H),7.20(t,J=7.8,2H),7.17(d,J=7.6,1H),7.01(t,J=7.4,1H),3.45(s,3H),2.46(s,3H).
13C NMR(125MHz,CDCl3)δ171.5,167.8,138.3,136.6,134.9,134.8,134.6,133.8,133.2,131.4,130.7,130.4,128.7,128.2,128.0,126.8,126.7,126.6,125.0,123.9,119.4,52.2,19.8.
根据以上数据推断所得产物的结构:
实施例35
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔3-氨基-N-丁基-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化,加入乙酸乙酯萃取,合并有机相(重复以上操作3次以上),使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率32%。
所得产物的结构表征数据如下:
1H NMR(500MHz,DMSO)δ11.50(s,1H),8.55(t,J=5.3,1H),8.07(d,J=8.2,1H),7.57(t,J=7.8,1H),7.46(t,J=7.7,1H),7.41(d,J=7.3,1H),7.36(d,J=7.9,1H),7.04(d,J=6.7,1H),3.33(s,1H),3.28(dd,J=12.8,6.7,2H),2.87(s,3H),1.53(dt,J=14.5,7.1,2H),1.37–1.30(m,2H),0.92(t,J=7.3,3H);
13C NMR(125MHz,DMSO)δ171.0,162.2,141.4,137.8,136.9,135.3,131.8,131.4,129.1,125.1,124.5,122.6,116.6,115.0,39.3,31.0,24.4,20.2,14.1.
根据以上数据推断所得产物的结构:
实施例36
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔1-碘-2-萘甲酸甲酯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率51%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.99(d,J=8.7,1H),7.91–7.84(m,2H),7.53(t,J=7.0,1H),7.46–7.37(m,3H),7.32(d,J=8.5,1H),7.10(d,J=8.0,1H),3.67(s,3H),3.25(s,3H),2.46(s,3H).
13C NMR(125MHz,CDCl3)δ169.0,167.7,140.4,137.8,135.7,134.6,133.2,132.7,129.5,129.0,127.9,127.8,127.8,127.6,127.5,127.2,126.5,125.5,51.9,51.3,20.2.
根据以上数据推断所得产物的结构:
实施例37
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔1-(1-碘萘-2-基)乙烷-1-酮,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率67%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.89-7.82(m,2H),7.75(d,J=8.6,1H),7.53–7.46(m,2H),7.45–7.39(m,2H),7.36(d,J=7.6,1H),7.15(d,J=7.5,1H),3.25(s,3H),2.46(s,3H),2.10(s,3H).
13C NMR(125MHz,CDCl3)δ203.0,168.8,137.3,137.0,136.9,136.1,134.2,134.0,131.9,130.3,129.5,128.0,127.7,127.5,127.3,126.6,124.5,51.4,30.0,20.0.
根据以上数据推断所得产物的结构:
实施例38
在氮气保护下,向反应容器中依次加入0.3毫摩尔苯甲酸,0.45毫摩尔N-丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率75%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.85(d,J=7.7,1H),7.54(t,J=7.5,1H),7.45(dd,J=13.3,7.1,2H),7.30(t,J=7.6,1H),7.24(d,J=7.5,1H),7.20(d,J=7.6,1H),6.56(s,1H),3.77(s,3H),3.22–3.12(m,1H),2.97–2.83(m,1H),1.89(s,3H),0.98–0.92(m,4H),0.73(d,J=6.5,3H).
13C NMR(125MHz,CDCl3)δ169.7,169.2,140.4,137.4,137.1,135.3,132.4,130.8,130.7,130.7,129.0,127.6,127.6,125.2,52.5,39.0,31.1,20.1,19.7,13.6.
根据以上数据推断所得产物的结构:
实施例39
在氮气保护下,向反应容器中依次加入0.3毫摩尔4-(甲硫基)苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率67%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.71(s,1H),7.75(d,J=8.3,1H),7.56(d,J=7.5,1H),7.35(t,J=7.6,1H),7.29(d,J=7.5,1H),7.23(d,J=7.9,2H),7.18(t,J=7.7,3H),7.03–6.95(m,2H),3.82(s,3H),2.39(s,3H),1.92(s,3H).
13C NMR(125MHz,CDCl3)δ169.3,167.8,145.6,140.7,138.0,137.3,136.9,135.6,131.3,129.5,128.7,127.8,126.6,126.0,125.5,124.5,123.9,119.5,52.6,20.0,14.7.
根据以上数据推断所得产物的结构:
实施例40
在氮气保护下,向反应容器中依次加入0.3毫摩尔4-氟苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率77%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.66(s,1H),7.87(dd,J=8.7,5.7,1H),7.55(d,J=7.5,1H),7.37(t,J=7.6,1H),7.31(d,J=7.5,1H),7.25(d,J=8.5,2H),7.19(t,J=7.9,2H),7.05(td,J=8.4,2.6,1H),7.00(t,J=7.3,1H),6.94(dd,J=8.8,2.5,1H),3.84(s,3H),1.93(s,3H).
13C NMR(125MHz,CDCl3)δ168.2(d,J=135Hz),165.6,163.6,143.2,138.0,136.9,136.4,135.4,131.8(d,J=9Hz),131.5,128.8,128.2,126.5,125.5,124.0,119.5,118.1(d,J=23Hz),115.1(d,J=23Hz),52.9,20.0.
根据以上数据推断所得产物的结构:
实施例41
在氮气保护下,向反应容器中依次加入0.3毫摩尔4-氯苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率68%。
所得产物的结构表征数据如下:
H NMR(500MHz,CDCl3)δ8.66(s,1H),7.78(d,J=8.4,1H),7.55(d,J=7.5,1H),7.36–7.33(m,2H),7.30(d,J=7.5,1H),7.25(d,J=7.8,2H),7.22(d,J=1.8,1H),7.19(t,J=7.9,2H),7.00(t,J=7.3,1H),3.83(s,3H),1.92(s,3H).
13C NMR(125MHz,CDCl3)δ168.8,167.5,141.9,138.7,138.0,136.9,136.2,135.5,131.5,130.6,130.5,128.8,128.7,128.2,128.1,125.5,124.0,119.5,52.9,20.0.
根据以上数据推断所得产物的结构:
实施例42
在氮气保护下,向反应容器中依次加入0.3毫摩尔4-碘苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率64%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.64(s,1H),7.73(dd,J=8.2,1.6,1H),7.60(s,1H),7.54(t,J=9.1,2H),7.36(t,J=7.6,1H),7.30(d,J=7.6,1H),7.26–7.24(m,2H),7.21(d,J=7.4,2H),7.01(t,J=7.2,1H),3.82(s,3H),1.92(s,3H).
13C NMR(125MHz,CDCl3)δ169.1,167.5,141.6,139.2,138.0,137.1,136.9,136.1,135.6,131.5,130.4,130.3,129.8,128.8,128.2,125.5,124.0,119.6,99.7,52.9,20.1.
根据以上数据推断所得产物的结构:
实施例43
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲氧基苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率72%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.10(s,1H),7.54(d,J=7.5,1H),7.34(t,J=7.0,4H),7.29(d,J=7.4,1H),7.18(t,J=7.8,2H),6.98(t,J=7.3,1H),6.86(d,J=8.4,1H),6.78(d,J=7.6,1H),3.83(s,3H),3.75(s,3H),2.05(s,3H).
13C NMR(125MHz,CDCl3)δ170.0,167.7,156.2,138.9,138.4,137.8,136.2,135.5,131.9,131.4,128.5,128.2,125.8,123.7,122.2,121.6,119.4,110.7,56.0,52.7,19.8.
根据以上数据推断所得产物的结构:
实施例44
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻苯基苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率51%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.35(s,1H),7.56(d,J=7.5,1H),7.46(t,J=7.7,1H),7.43–7.38(m,5H),7.36–7.30(m,5H),7.22–7.18(m,3H),6.99(t,J=7.3,1H),3.41(s,3H),2.03(s,3H).
13C NMR(125MHz,CDCl3)δ171.9,167.8,140.1,140.1,138.3,138.1,137.9,136.4,135.9,131.8,131.4,130.6,129.4,128.7,128.5,128.4,128.3,128.0,127.7,125.7,123.8,119.4,52.4,19.9.
根据以上数据推断所得产物的结构:
实施例45
在氮气保护下,向反应容器中依次加入0.3毫摩尔2,4-二甲氧基苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率61%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.28(s,1H),7.55(d,J=7.5,1H),7.38–7.32(m,3H),7.30–7.25(m,1H),7.20(t,J=7.8,2H),6.99(t,J=7.4,1H),6.39(d,J=1.5,1H),6.27(d,J=1.4,1H),3.81(s,3H),3.74(s,3H),3.70(s,3H),2.06(s,3H).
13C NMR(125MHz,CDCl3)δ170.0,167.7,162.3,158.1,140.7,138.5,137.5,136.0,135.9,131.4,128.6,128.1,125.8,123.6,119.4,115.0,105.7,98.3,55.9,55.5,52.6,19.6.
根据以上数据推断所得产物的结构:
实施例46
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基-4-氯苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率66%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.12(s,1H),7.53(d,J=7.5,1H),7.37(d,J=7.9,2H),7.34(d,J=7.6,1H),7.29(d,J=7.5,1H),7.21(t,J=7.9,2H),7.01(t,J=7.4,1H),6.87(t,J=2.0,1H),6.82(d,J=1.6,1H),3.82(s,3H),3.75(s,3H),2.05(s,3H).
13C NMR(125MHz,CDCl3)δ169.3,167.3,157.0,140.2,138.3,137.7,137.4,136.1,134.3,131.5,128.7,128.7,128.6,125.9,123.8,121.6,120.9,119.4,111.5,56.3,52.9,19.8.
根据以上数据推断所得产物的结构:
实施例47
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基-4-氟苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率41%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.13(s,1H),7.53(d,J=7.6,1H),7.37(d,J=8.3,3H),7.29(d,J=7.6,1H),7.21(t,J=7.4,2H),7.01(t,J=7.4,1H),6.60(d,J=10.4,1H),6.53(d,J=8.3,1H),3.84(s,3H),3.76(d,J=0.5,3H),2.06(s,3H);
13C NMR(125MHz,CDCl3)δ169.4,167.4,165.2,163.2,158.2(d,J=10Hz),141.0(d,J=11Hz),138.4,137.7,136.0,134.7,131.5,128.7,128.6,125.9,123.8,119.4,118.6,108.8(d,J=22Hz),99.2(d,J=26Hz),56.3,52.9,19.7;
19F NMR(471MHz,CDCl3)δ-105.29(t,J=9Hz,1F).
根据以上数据推断所得产物的结构:
实施例48
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-萘甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率83%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.97(s,1H),8.40(s,1H),7.86(d,J=7.9,1H),7.76(d,J=7.9,1H),7.67(s,1H),7.61(d,J=7.7,1H),7.52–7.47(m,2H),7.37(t,J=7.6,1H),7.30(d,J=7.5,1H),7.18(d,J=7.9,2H),7.07(t,J=7.8,2H),6.88(t,J=7.4,1H),3.90(s,3H),1.90(s,3H);
13C NMR(125MHz,CDCl3)δ169.9,168.2,138.1 137.4,137.4,136.1,135.5,134.7,131.5,131.2,130.5,129.7,128.6,128.5,128.2,128.0,127.7,127.1,125.5,123.6,119.3,52.9,20.1;
根据以上数据推断所得产物的结构:
实施例49
在氮气保护下,向反应容器中依次加入0.3毫摩尔1-萘甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化直至PH=1,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率56%。
所得产物的结构表征数据如下:
1H NMR(400MHz,DMSO)δ10.24(s,1H),8.05–7.98(m,3H),7.69–7.58(m,2H),7.55(d,J=3.4,1H),7.49(s,2H),7.32(d,J=8.1,2H),7.26(d,J=8.4,1H),7.15(t,J=7.6,2H),6.96(t,J=7.3,1H),2.01(s,3H).
13C NMR(125MHz,DMSO)δ170.8,168.3,138.8,137.9,137.4,137.0,134.6,132.6,132.1,131.8,130.1,129.1,129.0,128.8,128.5,128.1,127.3,127.1,125.8,125.3,124.3,119.9,20.3.
根据以上数据推断所得产物的结构:
实施例50
在氮气保护下,向反应容器中依次加入0.3毫摩尔3-氯苯甲酸,0.45毫摩尔N-苯基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率45%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.63(s,1H),7.82(d,J=1.8,1H),7.53(d,J=7.5,1H),7.47(dd,J=8.2,1.9,1H),7.35(t,J=7.6,1H),7.30(d,J=7.6,1H),7.25(d,J=7.7,2H),7.20(t,J=7.8,2H),7.15(d,J=8.2,1H),7.01(t,J=7.3,1H),3.84(s,3H),1.91(s,3H).
13C NMR(125MHz,CDCl3)δ168.4,167.7,138.3,137.9,137.1,136.3,135.7,133.8,132.5,132.0,131.7,131.4,129.2,128.8,128.1,125.3,124.0,119.5,53.0,20.0.
根据以上数据推断所得产物的结构:
实施例51
在氮气保护下,向反应容器中依次加入0.3毫摩尔3-三氟甲基苯甲酸,0.45毫摩尔N-正丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率67%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.14(s,1H),7.80(dd,J=8.0,1.1,1H),7.43(d,J=7.4,1H),7.39–7.30(m,2H),7.28(d,J=6.5,1H),6.42(s,1H),3.81(s,3H),3.26–3.17(m,1H),2.94–2.83(m,1H),1.91(s,3H),1.00–0.93(m,4H),0.73(t,J=6.9,3H).
13C NMR(125MHz,CDCl3)δ169.3,167.6,144.2,136.9,136.3,135.1,131.5,131.4,131.0,130.1(q,J=33Hz),128.7(q,J=4Hz),128.1,126.1(q,J=4Hz),125.0,123.5(q,J=271Hz),52.8,39.0,31.2,20.0,19.7,13.4.
19F NMR(471MHz,CDCl3)δ-62.77(s,1F);
根据以上数据推断所得产物的结构:
实施例52
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-苯基苯甲酸,0.45毫摩尔N-正丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化直至PH=1,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率72%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.41(d,J=7.2,2H),7.33–7.26(m,4H),7.25–7.21(m,1H),7.18(t,J=7.5,1H),7.15–7.05(m,2H),6.84(s,1H),6.78–6.74(m,1H),3.17–2.95(m,2H),1.88(s,3H),1.19(d,J=9.3,2H),1.10–1.02(m,2H),0.71(t,J=7.3,3H).
13C NMR(125MHz,CDCl3)δ172.2,170.3,139.9,139.4,138.0,137.6,135.9,135.0,134.8,132.2,129.6,129.0,128.5,128.3,128.1,127.4,127.0,123.7,39.8,30.9,19.9,19.6,13.5.
根据以上数据推断所得产物的结构:
实施例53
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-苯基苯甲酸,0.45毫摩尔N-异丙基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。将反应液用稀盐酸酸化直至PH=1,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率69%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.49(d,J=7.2,2H),7.40(d,J=4.2,3H),7.38(d,J=7.7,2H),7.34(d,J=7.3,1H),7.30(d,J=7.3,1H),7.22(d,J=6.6,1H),6.89(t,J=4.4,1H),6.38(d,J=7.7,1H),4.01–3.93(m,1H),2.00(s,3H),1.07(d,J=6.6,3H),0.97(d,J=6.5,3H).
13C NMR(125MHz,CDCl3)δ171.3,170.2,139.9,139.6,138.3,137.7,136.0,135.2,134.9,132.4,129.7,129.1,128.5,128.4,128.2,127.6,127.0,123.6,42.4,22.1,22.1,20.0.
根据以上数据推断所得产物的结构:
实施例54
在氮气保护下,向反应容器中依次加入0.3毫摩尔1-萘甲酸,0.45毫摩尔1-碘代-N-苯基-2-萘酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率54%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ9.06(s,1H),8.02–7.99(m,2H),7.97(d,J=8.4,1H),7.90(t,J=8.1,2H),7.87(d,J=8.5,1H),7.66–7.62(m,1H),7.58(t,J=7.5,1H),7.54–7.50(m,1H),7.44–7.41(m,1H),7.39–7.35(m,2H),7.15(d,J=7.7,2H),7.05(t,J=7.9,2H),6.89(t,J=7.4,1H),3.58(s,3H).
13C NMR(125MHz,CDCl3)δ171.0,167.6,138.1,135.1,134.6,134.6,133.9,132.9,131.4,131.3,130.5,129.1,128.9,128.6,128.6,128.1,128.0,127.7,127.0,126.9,126.8,126.7,125.2,124.6,123.9,119.5,52.6.根据以上数据推断所得产物的结构:
实施例55
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基烟酸,0.45毫摩尔正丁基-1-碘-2-萘酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率52%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.31(d,J=5.1,1H),7.92(d,J=8.5,1H),7.87(d,J=8.2,1H),7.69(d,J=8.5,1H),7.50(t,J=7.3,1H),7.42(t,J=7.5,1H),7.37(d,J=8.4,1H),7.11(s,1H),6.90(d,J=5.1,1H),4.09(s,3H),3.45(s,3H),3.39–3.31(m,1H),3.01–2.93(m,1H),1.10–1.01(m,4H),0.79(t,J=7.1,3H);
13C NMR(125MHz,CDCl3)δ169.0,168.2,160.2,149.0,148.4,134.5,133.5,131.3,130.2,129.2,128.2,126.9,126.8,125.9,124.7,118.8,117.2,54.2,52.6,39.3,31.1,19.9,13.7;
根据以上数据推断所得产物的结构:
实施例56
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基烟酸,0.45毫摩尔N-正丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率62%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.25(d,J=5.1,1H),7.43(d,J=7.5,1H),7.32(t,J=7.6,1H),7.27(t,J=9.2,1H),6.99(d,J=7.3,1H),6.76(d,J=5.1,1H),4.03(s,3H),3.73(s,3H),3.35–3.22(m,1H),3.01–2.84(m,1H),2.02(s,3H),1.09–0.95(m,4H),0.77(t,J=6.9,3H).
13C NMR(125MHz,CDCl3)δ168.9,168.2,160.3,149.3,148.8,137.2,135.1,133.5,131.1,128.7,125.5,117.7,116.5,54.1,52.8,39.2,31.0,19.8,19.7,13.6.
根据以上数据推断所得产物的结构:
实施例57
在氮气保护下,向反应容器中依次加入0.3毫摩尔噻吩-2-羧酸,0.45毫摩尔N-正丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率69%。所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.57(d,J=5.0,1H),7.43–7.39(m,1H),7.33–7.28(m,2H),6.97(d,J=5.0,1H),5.93(s,1H),3.77(s,3H),3.26–3.20(m,1H),3.04–2.96(m,1H),2.00(s,3H),1.19–1.11(m,4H),0.83(t,J=7.0,3H).
13C NMR(125MHz,CDCl3)δ169.4,162.8,146.4,137.1,136.4,133.0,131.3,131.0,131.0,127.9,127.8,124.7,52.1,39.1,31.4,20.1,19.9,13.7.
根据以上数据推断所得产物的结构:
实施例58
在氮气保护下,向反应容器中依次加入0.3毫摩尔苯并呋喃-2-羧酸,0.45毫摩尔N-正丁基-2-碘-3-甲基苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为5:1的石油醚:乙酸乙酯的混合溶剂,产率31%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.62(d,J=8.4,1H),7.49(t,J=6.9,2H),7.42–7.38(m,2H),7.32(d,J=7.7,1H),7.29(d,J=7.1,1H),5.77(s,1H),3.86(s,3H),3.14–3.08(m,1H),3.04–2.98(m,1H),2.06(s,3H),1.06–0.97(m,4H),0.74(t,J=6.9,3H).
13C NMR(125MHz,CDCl3)δ169.0,160.3,154.5,140.5,138.0,137.4,131.4,128.6,128.4,128.4,127.6,127.4,125.2,124.2,122.1,112.3,52.4,39.2,31.2,20.1,19.8,13.6.
根据以上数据推断所得产物的结构:
实施例59
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2,5-二碘苯甲酸甲酯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率59%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.27(d,J=1.0,0.2H),8.00(d,J=8.5,1H),7.82(d,J=2.5,1H),7.39–7.34(m,1H),7.32(d,J=7.5,0.2H),7.26–7.23(m,1H),7.18(d,J=7.6,1H),7.15(dd,J=8.0,2.5,1H),7.04(t,J=7.0,0.3H),6.98(d,J=8.0,0.2H),3.92(s,3H),3.64(d,J=3.5,3.4H),3.52(s,0.6H),2.40(s,3.6H).
13C NMR(125MHz,CDCl3)δ169.7,169.1,166.6,166.0,141.3,140.9,140.1,138.7,137.8,135.9,135.4,134.9,132.9,132.4,132.3,131.8,130.8,129.9,129.6,129.5,129.0,126.9,126.6,93.0,92.5,52.5,52.1,52.0,51.6,20.0,19.7.
根据以上数据推断所得产物的结构:
实施例60
在氮气保护下,向反应容器中依次加入0.3毫摩尔苯甲酸,0.45毫摩尔1-(1-碘萘-2-基)乙烷-1-酮,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔4,4-二叔丁基联吡啶,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率57%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.14(dd,J=7.8,1.3,1H),7.92-7.87(m,2H),7.78(d,J=8.6,1H),7.62(td,J=7.5,1.3,1H),7.56(td,J=7.6,1.1,1H),7.53–7.49(m,1H),7.38–7.33(m,1H),7.30(d,J=8.4,1H),7.27–7.24(m,1H),3.46(s,3H),2.16(s,3H).
13C NMR(125MHz,CDCl3)δ202.6,166.9,140.1,139.0,135.5,134.3,132.2,132.1,131.9,131.1,130.4,128.1,128.0,127.7,127.2,126.9,126.7,124.5,51.9,30.0.
根据以上数据推断所得产物的结构:
实施例61
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基烟酸,0.45毫摩尔N-丁基-3-氯-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为3:1的石油醚:乙酸乙酯的混合溶剂,产率27%。所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.28(d,J=5.1Hz,1H),7.53(d,J=7.6Hz,1H),7.46(d,J=7.9Hz,1H),7.38(t,J=7.8Hz,1H),7.08(s,1H),6.77(d,J=5.1Hz,1H),4.04(s,3H),3.80(s,3H),3.34–3.22(m,1H),2.98–2.85(m,1H),1.06–0.97(m,4H),0.77(t,J=6.9Hz,3H).
13C NMR(125MHz,CDCl3)δ168.3,167.6,160.5,149.2,147.6,139.1,133.3,132.1,130.5,129.9,126.6,117.8,116.3,54.2,52.9,39.3,31.0,19.8,13.6.
根据以上数据推断所得产物的结构:
实施例62
在氮气保护下,向反应容器中依次加入0.3毫摩尔2-甲氧基烟酸,0.45毫摩尔N-丁基-3-溴-2-碘苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔3,4,7,8-四甲基-1,10-菲罗啉,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于120℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为3:1的石油醚:乙酸乙酯的混合溶剂,产率25%。
所得产物的结构表征数据如下:
1H NMR(400MHz,CDCl3)δ8.30(d,J=4.9,1H),7.66(d,J=7.9,1H),7.58(d,J=7.3,1H),7.33(d,J=8.0,1H),7.15(s,1H),6.77(d,J=4.7,1H),4.07(s,3H),3.82(s,3H),3.34–3.24(m,1H),2.93(d,J=6.9,1H),1.03(s,4H),0.80(d,J=6.2,3H).
13C NMR(100MHz,CDCl3)δ168.3,167.6,160.5,149.3,149.2,139.2,135.3,133.7,130.1,127.1,121.8,117.8,116.2,54.2,52.9,39.3,31.0,19.8,13.6.
根据以上数据推断所得产物的结构:
实施例63
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-三氟甲基碘苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率27%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ7.72(d,J=8.0,1H),7.50(t,J=8.0,1H),7.45(t,J=8.0,1H),7.33(t,J=7.5,1H),7.28–7.23(m,2H),7.12(d,J=7.5,1H),3.45(s,3H),2.43(s,3H).
13C NMR(100MHz,CDCl3)δ169.05,139.3(q,J=2.0),137.84,135.81,132.94,131.92,131.65,131.42,130.75,130.52,129.93,128.68,128.39,127.56,127.4(q,J=2.0),126.0(q,J=5.0),125.66,125.33,122.61,51.45,20.11;
19F NMR(471MHz,CDCl3)δ-57.73(s,3F).
根据以上数据推断所得产物的结构:
实施例64
在氮气保护下,向反应容器中依次加入0.3毫摩尔邻甲基苯甲酸,0.45毫摩尔2-碘-N-(4-甲基-2-氧代-2H-苯并吡喃-7-基)苯甲酰胺,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,再一次加入1.5毫摩尔碘甲烷,0.6毫摩尔碳酸钾,于60℃下搅拌反应2h。反应完成后,将反应液用饱和碳酸氢钠水洗,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为20:1的石油醚:乙酸乙酯的混合溶剂,产率16%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.96(s,1H),7.78(d,J=7.2,1H),7.48(dd,J=14.9,7.4,2H),7.42(q,J=8.9,2H),7.26(d,J=5.4,1H),7.18(d,J=8.3,3H),7.06(d,J=7.5,1H),6.14(s,1H),3.77(s,3H),2.44(s,3H),2.35(s,3H).
13C NMR(15MHz,CDCl3)δ171.6,167.5,161.0,154.1,152.1,141.6,138.7,137.8,136.3,135.3,132.1,130.2,130.1,130.0,129.3,128.8,128.4,127.3,125.1,115.9,115.1,113.2,106.4,52.6,19.7,18.5.
根据以上数据推断所得产物的结构:
实施例65
在氮气保护下,向反应容器中依次加入0.3毫摩尔间三氟甲基苯甲酸,0.45毫摩尔1-氟-4-碘-2-异丙基-5-甲氧基苯,0.015毫摩尔的二碘(对伞花烃)钌(II)二聚体,0.03毫摩尔三辛基膦,0.36毫摩尔碳酸钾,2毫升N-甲基吡咯烷酮,于100℃下搅拌反应24h,停止加热和搅拌,冷却至室温。反应完成后,加入稀盐酸酸化直到PH=1~2,乙酸乙酯萃取,使用无水硫酸镁干燥,过滤,减压蒸馏去除溶剂,并通过柱层析分离纯化,得到目标产物,所用的柱层析洗脱液为体积比为80:20:1的石油醚:乙酸乙酯:甲酸的混合溶剂,产率84%。
所得产物的结构表征数据如下:
1H NMR(500MHz,CDCl3)δ8.19(s,1H),7.81(d,J=7.9,1H),7.46(d,J=8.0,1H),7.10(d,J=8.4,1H),6.59(d,J=11.9,1H),3.67(s,3H),3.21(dt,J=13.8,6.9,1H),1.26(d,J=6.9,6H).
13C NMR(125MHz,CDCl3)δ172.4(s),162.1(s),160.2(s),154.9(d,J=10.2),142.4(s),132.4(s),131.2(s),129.5(q,J=33.3),128.1(d,J=7.4),127.9(dd,J=215.1,3.6),127.2(d,J=15.4),124.3(d,J=3.3),123.7(q,J=272.4),99.1(d,J=27.7),55.3(s),26.8(s),22.7(s).
根据以上数据推断所得产物的结构:
图1为实施例1所得目标产物的氢谱图;图2为实施例11所得目标产物的氢谱图;图3为实施例19所得目标产物的氢谱图;图4为实施例21所得目标产物的氢谱图;图5为实施例24所得目标产物的氢谱图;图6为实施例65所得目标产物的氢谱图。
Claims (10)
1.一种2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:包括如下步骤:在保护性氛围下,以有机溶剂为反应介质,将芳基羧酸与芳基卤化物在钌催化剂,配体和碱性化合物的作用下反应,获得2,2'-联苯基-1-羧酸衍生物;
其中R1为甲基、甲氧基、苯基、氢;
R2为氢、甲基、氟、氯、甲氧基或三氟甲基;
R3为氢、甲基、甲氧基、甲硫基、N,N-二甲基、氟、氯或碘;
X为碘或溴;
R4为氢,烷基,甲氧基,卤素,三氟甲基,甲氧基,甲硫基,N,N-二甲基,乙酰氧基,苯基,萘基,氰基,乙酰基,烯基,萘基,氨基;
R5为氢,新戊酰胺基,N-正丁基甲酰胺基,N-(4-氟苯基)甲酰胺基、N-(3-腈基苯基)甲酰胺基、N-(3,4-二氯苯基)甲酰胺基,N-(2-溴-3-甲基苯基)甲酰胺基、N-异丙基甲酰胺基,N-叔丁基甲酰胺基、N-苄基甲酰胺基、N-苯基甲酰胺基、甲酰胺基、N,N-二甲基甲酰胺基、对氟苯基甲酰胺基、对氰基苯基甲酰胺基、CH3OCO-、乙酮基、
R4与R5不同时为氢;R4与R5的基团能相互替换;
R6为氢、甲基、MeO-C=O-、异丙基;R7为氢、酯基,碘、氟;
R8为丁基或苯基;R9为CH3O或CH3;
所述钌催化剂为二碘(对伞花烃)钌(II)二聚体或二氯(对伞花烃)钌(II)二聚体;
所述配体为三-环己基膦,三-甲基膦,三-丁基膦,三-辛基膦,二苯基甲基膦,三苯基膦,甘氨酸,N-Boc-L-缬氨酸,L-叔亮氨酸,L-脯氨酸,二金刚烷基正丁基膦,二-环己基-苯基膦,[1,1'-联苯]-2-基二-环己基膦,三(4-甲氧基苯基)膦,三呋喃基膦,哌啶-2-羧酸,5-(三氟甲基)吡啶-2-醇,联吡啶,4,4-二甲氧基联吡啶,4,4-二叔丁基联吡啶,菲罗啉,5H-环戊[2,1-b:3,4-b']联吡啶-5-酮,1,10-菲罗啉-5,6-二酮,2,9-二甲基-菲罗啉,3,4,7,8-四甲基-1,2-菲罗啉,4,7-二苯基菲罗啉,4,7-二甲氧基-菲罗啉,(E)-N-苄基-1-(吡啶-2-基)甲苯胺,2E,3E)-N2,N3-二苯基丁烷-2,3-二亚胺,(2E,3E)-N2,N3-二异丙基丁烷-2,3-二亚胺,(2E,3E)-N2,N3双(2,6-二异丙基苯基)丁烷-2,3-二亚胺,N-苄基吡啶酰胺,N-(2-羟乙基)吡啶酰胺,N、N'-(乙烷-1,2-二酰基)二苯磺酰胺或[2,2'-联吡啶]-6,6'-二醇。
2.根据权利要求1所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:
R4中所述烷基为C1~3烷基,
R4中所述卤素为氟,氯,溴或碘;
所述配体为三-辛基膦或3,4,7,8-四甲基菲罗啉中一种以上;
所述碱性化合物为碳酸钾。
3.根据权利要求1所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:
所述反应的温度为100~120℃,反应的时间为20~26小时;
所述芳基羧酸与芳基卤化合物的摩尔比为1:1.5~2;所述钌催化剂与芳基羧酸的摩尔比为(0.025~0.05):1;所述配体与芳基羧酸的摩尔比为(0.05~0.10):1。
4.根据权利要求1所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:所述有机溶剂为N-甲基吡咯烷酮或N,N-二甲基甲酰胺中一种以上;所述保护性氛围为氮气。
5.根据权利要求1所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:
反应完后进行后续处理;所述后续处理是指冷却,加入稀酸至体系的pH=0.5~1.5,萃取,去除有机相中溶剂、分离纯化;此时2,2'-联苯基-1-羧酸衍生物为2,2'-联苯基-1-羧酸化合物。
6.根据权利要求5所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:
所述后续处理是指调节体系的pH=0.5~1.5,乙酸乙酯萃取,旋去除有机相中溶剂,柱层析分离;
所述去除有机相中溶剂是指去除有机相中水,去除有机溶剂;
所述去除有机相中水是指采用干燥剂进行干燥,干燥剂为无水硫酸镁,然后过滤;所述去除有机相中有机溶剂是指减压蒸馏去除有机溶剂;
所述柱层析的洗脱液为石油醚和乙酸乙酯的混合溶剂,或者石油醚、乙酸乙酯和甲酸的混合溶剂。
7.根据权利要求1所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:反应完后,或者将反应体系中的产物进行甲基化,然后进行后续处理;
此时2,2'-联苯基-1-羧酸衍生物为2,2'-联苯基-1-羧酸甲酯化合物。
8.根据权利要求7所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:所述甲基化是指将反应体系与碘甲烷以及碱性化合物混合,反应;
所述后续处理是指淬灭反应、萃取、去除有机相中溶剂、分离纯化。
9.根据权利要求8所述2'-取代的2,2'-联苯基-1-羧酸衍生物的合成方法,其特征在于:所述后续处理是指淬灭反应,乙酸乙酯萃取,旋去除有机相中溶剂,柱层析分离;所述去除有机相中溶剂是指去除有机相中水,去除有机溶剂;
所述淬灭反应是指向反应体系中加入饱和碳酸氢钠溶液;所述去除有机相中水是指采用干燥剂进行干燥,干燥剂为无水硫酸镁,然后过滤;所述去除有机相中有机溶剂是指减压蒸馏去除有机溶剂;
所述柱层析的洗脱液为石油醚和乙酸乙酯的混合溶剂,或者石油醚、乙酸乙酯和甲酸的混合溶剂。
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