CN109020860A - 一种2-芳基-3-酯基多取代吡咯类化合物及其合成精制方法 - Google Patents
一种2-芳基-3-酯基多取代吡咯类化合物及其合成精制方法 Download PDFInfo
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
本发明属于化学合成领域,涉及一系列2‑芳基‑3‑酯基多取代吡咯类化合物及其合成精制方法。所述化合物的结构通式如式(Ⅰ)所示,其中R1=芳基或杂环基,R2=酯基或氰基。该合成方法以烯胺酯类化合物为原料,通过2‑碘酰基苯甲酸促进氧化环化生成2‑芳基‑3‑酯基多取代吡咯类化合物,操作简单,制备成本较低,相对收率和纯度更高,环境污染少。
Description
技术领域
本发明属于化学合成领域,具体而言,涉及一系列2-芳基-3-酯基多取代吡咯类化合物及其合成精制方法。
背景技术
吡咯结构已成为各种杂环化合物中最重要的核心骨架之一,作为一种重要的五元氮杂环化合物,其具有多种生物活性和药理活性,常出现在天然产物和重要的药物化合物中。另外,吡咯结构仍然是许多导电功能材料的重要组成部分,不仅如此,多取代吡咯类化合物在生物有机化学、植物化学和材料化学领域起着非常重要的作用。
由于多取代吡咯类化合物具有独特的生物活性和广泛的用途,近几年来,多取代吡咯类化合物的制备一直是有机合成化学中的研究热点。然而,传统构建吡咯环的方法都是由预先合成的中间体经过多步反应得到的,如经典的Hantzsch,Paal-Knorr和Knorr反应。最近,一些简单高效合成吡咯的方法被报道,包括杂原子取代不饱和化合物的环化反应、过渡金属催化的C-H活化反应和多组分反应等(文献Toh,K.K.;Wang,Y.-F.;Ng,E.P.J.;Chiba,S.J.Am.Chem.Soc.2011,133,13942)。本发明人在多取代吡咯类化合物的合成研究过程中,找到了一种新型的2-芳基-3-酯基多取代吡咯类化合物的合成方法,为吡咯衍生物的合成拓展了一条新路径。
发明内容
鉴于多取代吡咯类化合物独特性能和广泛应用,本发明人通过大量实验,建立了一种简单实用的2-芳基-3-酯基多取代吡咯类化合物制备方法,合成了一系列不同芳基和酯基取代的2-芳基-3-酯基多取代吡咯类化合物。
基于发明人实验结果,本发明的第一个目的在于提供一系列2-芳基-3-酯基多取代吡咯类化合物,结构通式如式(Ⅰ)所示:
其中R1=芳基或杂环基,R2=酯基或氰基。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中R1中所述芳基选自C6~C10芳基。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中R1中所述芳基被1~2个烷基、烷氧基、卤素或苯基取代,所述杂环基为噻吩基。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中R1中所述烷基、烷氧基的碳原子数为1~2。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中R2中所述酯基为-CO2R,R为C1~C4烷烃基或C6~C10芳基。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中R2中所述酯基为-CO2R,R为C1~C2烷烃基或苯基。
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物,其中该类化合物选自如下的任一种:
另外,本发明的第二个目的在于提供一种上述2-芳基-3-酯基多取代吡咯类化合物的合成方法,该方法以烯胺酯类化合物为原料,2-碘酰基苯甲酸为氧化剂,反应式如下:
进一步优选地,如上所述2-芳基-3-酯基多取代吡咯类化合物的合成方法,该方法中反应在空气环境中进行,具体是将烯胺酯类化合物溶解于四氢呋喃中,然后加入2-碘酰基苯甲酸,烯胺酯类化合物与2-碘酰基苯甲酸的摩尔比为1:(1.0~1.5),110~130℃回流反应8~16小时,得到2-芳基-3-酯基多取代吡咯类化合物的粗产物。
最后,本发明的第三个目的在于提供一种2-芳基-3-酯基多取代吡咯类化合物的精制方法,该方法包括将权利要求8反应所得2-芳基-3-酯基多取代吡咯类化合物的粗产物中加入乙酸乙酯和水,萃取,有机相备用,水相用再用乙酸乙酯萃取1~3次,然后合并有机相,无水硫酸钠干燥,过滤后减压浓缩,硅胶柱层析纯化,洗脱液是体积比为(2.8-3.2):1的石油醚-乙酸乙酯,得到2-芳基-3-酯基多取代吡咯类化合物纯品。
与现有技术相比,本发明提供的2-芳基-3-酯基多取代吡咯类化合物是一种结构新颖、具有多种潜在应用价值的活性物质。另外,本发明合成方法通过2-碘酰基苯甲酸促进氧化环化生成2-芳基-3-酯基多取代吡咯类化合物,该方法操作简单,制备成本较低,相对收率和纯度更高,环境污染少,取得到了较为理想的效果,是目前报道的2-芳基-3-酯基多取代吡咯类化合物合成的比较高效的方法之一。
附图说明
图1为化合物2a的的1H NMR氢谱图;
图2为化合物2a的的13C NMR碳谱图;
图3为化合物2b的的1H NMR氢谱图;
图4为化合物2b的的13C NMR碳谱图;
图5为化合物2e的的1H NMR氢谱图;
图6为化合物2e的的13C NMR碳谱图;
图7为化合物2g的的1H NMR氢谱图;
图8为化合物2g的的13C NMR碳谱图;
图9为化合物2j的的1H NMR氢谱图;
图10为化合物2j的的13C NMR碳谱图;
图11为化合物2n的的1H NMR氢谱图;
图12为化合物2n的的13C NMR碳谱图;
图13为化合物2o的的1H NMR氢谱图;
图14为化合物2o的的13C NMR碳谱图;
图15为化合物2p的的1H NMR氢谱图;
图16为化合物2p的的13C NMR碳谱图;
图17为化合物2q的的1H NMR氢谱图;
图18为化合物2q的的13C NMR碳谱图;
图19为化合物2r的的1HNMR氢谱图;
图20为化合物2r的的13C NMR碳谱图;
图21为化合物2s的的1HNMR氢谱图;
图22为化合物2s的的13C NMR碳谱图。
具体实施方式
以下是本发明的具体实施例,对本发明的技术方案做进一步作描述,但是本发明的保护范围并不限于这些实施例。凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。其中,各实施例的原料烯胺酯的结构式如下表所示。
实施例1:2-苯基-1H-吡咯-3-甲酸甲酯2a的合成,其结构式具体如下:
将1mmol烯胺酯1a和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率84%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.60(s,1H),7.55-7.58(m,2H),7.33-7.41(m,3H),6.71-6.73(m,2H),3.72(s,3H).13C NMR(100MHz,CDCl3):δ 165.6,137.3,132.1,129.0,128.4,128.3,117.9,112.2,111.9,51.1.HRMS(ESI):m/z calcd for C12H11NNaO2[M+Na]+224.0682,found:224.0682.
实施例2:2-(邻甲苯基)-1H-吡咯-3-甲酸甲酯2b的合成,其结构式具体如下:
将1mmol烯胺酯1b和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率90%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.23(s,1H),7.22-7.31(m,5H),6.77-6.78(m,1H),6.72-6.74(m,1H),3.67(s,3H),2.20(s,3H).13C NMR(100MHz,CDCl3):δ 165.2,138.0,132.4,130.4,130.1,128.9,125.5,117.4,111.0,86.4,51.0,20.0.HRMS(ESI):m/z calcdfor C13H13NNaO2[M+Na]+238.0838,found:238.0839.
实施例3:2-(间甲苯基)-1-吡咯-3-羧酸甲酯2c的合成,其结构式具体如下:
将1mmol烯胺酯1c和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率92%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.43(s,1H),7.38-7.40(m,2H),7.28-7.32(m,1H),7.17-7.19(m,1H),6.72-6.75(m,2H),3.74(s,3H),2.39(s,3H).13C NMR(100MHz,CDCl3):δ165.5,138.0,137.5,132.1,129.5,129.2,128.2,126.3,117.7,112.3,111.9,51.1,21.6.HRMS(ESI):m/z calcd for C13H13NNaO2[M+Na]+238.0838,found:238.0834.
实施例4:2-(对甲苯基)-1-吡咯-3-羧酸甲酯2d的合成,其结构式具体如下:
将1mmol烯胺酯1d和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率92%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.38(s,1H),7.48(d,J=8.1Hz,2H),7.23-7.23(m,1H),7.21-7.21(m,1H),6.72-6.75(m,2H),3.75(s,3H),2.39(s,3H).13C NMR(100MHz,CDCl3):δ165.5,138.4,137.5,129.3,129.1,128.9,117.6,112.3,111.8,51.1,21.5.HRMS(ESI):m/zcalcd for C13H13NNaO2[M+Na]+238.0838,found:238.0837.
实施例5:2-(3,4-二甲基苯基)-1H-吡咯-3-羧酸甲酯2e的合成,其结构式如下:
将1mmol烯胺酯1e和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率87%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.52(s,1H),7.31-7.33(m,2H),7.15-7.16(m,1H),6.68-6.71(m,2H),3.73(s,3H),2.29(s,3H),2.28(s,3H).13C NMR(100MHz,CDCl3):δ165.6,137.6,137.0,136.4,130.0,129.7,129.6,126.6,117.5,112.1,111.5,51.0,19.9,19.7.HRMS(ESI):m/z calcd for C14H15NNaO2[M+Na]+252.0995,found:252.0992.
实施例6:2-(2,4-二甲基苯基)-1H-吡咯-3-羧酸甲酯2f的合成,其结构式如下:
将1mmol烯胺酯1f和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率53%
其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.19(s,1H),7.16(d,J=7.7Hz,1H),7.09(s,1H),7.04(d,J=7.7Hz,1H),6.75-6.76(m,1H),6.71-6.72(m,1H),3.68(s,3H),2.36(s,3H),2.16(s,3H).13C NMR(100MHz,CDCl3):δ 165.2,138.6,137.8,130.9,130.2,129.5,126.2,117.2,113.4,111.0,110.2,51.0,21.4,19.9.HRMS(ESI):m/z calcd for C14H15NNaO2[M+Na]+252.0995,found:252.0994.
实施例7:2-(4-甲氧基苯基)-1-吡咯-3-羧酸甲酯2g的合成,其结构式具体如下:
将1mmol烯胺酯1g和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率75%。其主要理化性质如下:
1HNMR(400MHz,CDCl3):δ 8.65(s,1H),7.48(d,J=8.9Hz,2H),6.90(d,J=8.9Hz,2H),6.66-6.70(m,2H),3.81(s,3H),3.72(s,3H).13C NMR(100MHz,CDCl3):δ 165.7,159.7,137.4,130.3,124.6,117.5,113.7,112.0,111.2,55.4,51.0.HRMS(ESI):m/z calcd forC13H13NNaO3[M+Na]+254.0788,found:254.0781.
实施例8:2-(3-甲氧基苯基)-1H-吡咯-3-甲酸甲酯2h的合成,其结构式具体如下:
将1mmol烯胺酯1h和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率81%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.51(s,1H),7.29-7.33(m,1H),7.13-7.14(m,2H),6.89-6.92(m,1H),6.72-6.75(m,2H),3.83(s,3H),3.75(s,3H).13C NMR(100MHz,CDCl3):δ165.4,159.5,137.0,133.4,129.3,121.3,117.8,114.7,114.2,112.4,112.1,55.5,51.1.HRMS(ESI):m/z calcd for C13H13NNaO3[M+Na]+254.0788,found:254.0788.
实施例9:2-(3,4-二甲氧基苯基)-1H-吡咯-3-甲酸甲酯2i的合成,其结构式具体如下:
将1mmol烯胺酯1i和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率81%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.92(s,1H),7.17-7.18(m,1H),7.06-7.08(m,1H),6.82(d,J=8.4Hz,1H),6.66-6.68(m,2H),3.84(s,3H),3.81(s,3H),3.71(s,3H).13C NMR(100MHz,CDCl3):δ 165.7,149.1,148.4,137.2,124.9,121.4,117.3,112.8,112.1,111.3,110.9,55.9,51.0.HRMS(ESI):m/z calcd for C14H15NNaO4[M+Na]+284.0893,found:284.0890.
实施例10:2-(4-氟苯基)-1-吡咯-3-羧酸甲酯2j的合成,其结构式具体如下:
将1mmol烯胺酯1j和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率85%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.38(s,1H),7.55-7.58(m,2H),7.10(t,J=8.7Hz,2H),6.77(t,J=2.8Hz,1H),6.73(t,J=2.9Hz,1H),3.75(s,3H).13C NMR(100MHz,CDCl3):δ165.4,164.1,161.6,136.4,130.9(d,JC-F=8.3Hz),117.8,115.5,115.3,112.4,51.2.HRMS(ESI):m/z calcd for C12H10FNNaO2[M+Na]+242.0588,found:242.0587.
实施例11:2-(4-氯苯基)-1-吡咯-3-羧酸甲酯2k的合成,其结构式具体如下:
将1mmol烯胺酯1k和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率85%。其主要理化性质如下:
1HNMR(400MHz,CDCl3):δ 8.53(s,1H),7.51(d,J=8.5Hz,2H),7.37(d,J=8.5Hz,2H),6.73-6.76(m,2H),3.74(s,3H).13C NMR(100MHz,CDCl3):δ 165.4,137.0,134.4,130.6,130.3,128.5,118.2,112.5,112.4,51.2.HRMS(ESI):m/z calcd for C12H10ClNNaO2[M+Na]+258.0292,found:258.0287.
实施例12:2-(3-氯苯基)-1-吡咯-3-羧酸甲酯2l的合成,其结构式具体如下:
将1mmol烯胺酯1l和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率84%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.58(s,1H),7.56-7.56(m,1H),7.46-7.49(m,1H),7.31-7.33(m,2H),6.72-6.77(m,2H),3.75(s,3H).13C NMR(100MHz,CDCl3):δ 165.3,135.5,134.2,133.8,129.5,128.9,128.4,127.3,118.4,112.6,51.2.HRMS(ESI):m/zcalcd for C12H10ClNNaO2[M+Na]+258.0292,found:258.0292
.实施例13:2-(4-溴苯基)-1-吡咯-3-羧酸甲酯2m的合成,其结构式具体如下:
将1mmol烯胺酯1m和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率80%。其主要理化性质如下:
白色固体,熔点:175-177℃;1H NMR(400MHz,CDCl3):δ 8.09(br,1H),7.68-7.69(m,1H),7.50-7.56(m,3H),7.42-7.46(m,2H),7.28-7.35(m,2H),3.80(s,3H),3.61(s,3H);13C NMR(100MHz,CDCl3):δ 173.9,167.1,162.7,152.0,136.1,134.7,134.3,131.5,130.3,130.0,129.1,128.9,128
实施例14:2-([1,1'-联苯基]-4-基)-1H-吡咯-3-羧酸甲酯2n的合成,结构式如下:
将1mmol烯胺酯1n和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率92%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.55(s,1H),7.60-7.68(m,6H),7.44-7.48(m,2H),7.35-7.39(m,1H),6.75-6.78(m,2H),3.77(s,3H).13C NMR(100MHz,CDCl3):δ 165.6,141.1,140.7,137.0,131.0,129.3,129.0,127.6,127.2,127.0,118.0,112.5,112.1,51.2.HRMS(ESI):m/z calcd for C20H17NNaO4[M+Na]+358.1050,found:358.1057.
实施例15:2-(萘-2-基)-1-吡咯-3-羧酸甲酯2o的合成,其结构式具体如下:
将1mmol烯胺酯1o和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率77%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.45(s,1H),7.88-7.92(m,2H),7.65-7.67(m,1H),7.46-7.54(m,3H),7.40-7.44(m,1H),6.83-6.85(m,2H),3.53(s,3H).13C NMR(100MHz,CDCl3):δ 165.2,135.3,133.6,132.7,130.5,129.2,128.4,128.4,126.5,126.1,125.8,125.1,117.9,114.5,111.4,51.0.HRMS(ESI):m/z calcd for C16H13NNaO2[M+Na]+247.0838,found:247.0839.
实施例16:2-(噻吩-2-基)-1H-吡咯-3-甲酸甲酯2p的合成,其结构式具体如下:
将1mmol烯胺酯1p和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率89%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.50(s,1H),7.52-7.53(m,1H),7.34-7.35(m,1H),7.07-7.10(m,1H),6.72-6.75(m,2H),3.81(s,3H).13C NMR(100MHz,CDCl3):δ 165.2,133.2,130.5,127.4,127.4,126.1,118.0,112.6,112.4,51.2.HRMS(ESI):m/z calcd forC10H9NNaO2S[M+Na]+230.0246,found:230.0248.
实施例17:2-苯基-1h-吡咯-3-腈基2q的合成,其结构式具体如下:
将1mmol烯胺酯1q和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率47%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.74(s,1H),7.68-7.71(m,2H),7.45-7.49(m,2H),7.37-7.40(m,1H),6.82-6.84(m,1H),6.56-6.57(m,1H).13C NMR(100MHz,CDCl3):δ 139.1,129.9,129.4,129.9,125.9,119.2,117.6,114.0,90.5.HRMS(ESI):m/z calcd forC11H8N2Na[M+Na]+191.0580,found:191.0576.
实施例18:2-苯基-1-吡咯-3-羧酸乙酯2r的合成,其结构式具体如下:
将1mmol烯胺酯1r和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率77%。其主要理化性质如下:
白色固体,熔点:170-171℃;1H NMR(400MHz,CDCl3):δ 9.10(br,1H),8.30-8.31(m,1H),7.65-7.67(m,1H),7.41-7.44(m,2H),7.29-7.34(m,2H),3.77(s,3H),3.67(s,3H);13C NMR(100MHz,CDCl3):δ 174.8,167.5,163.4,147.1,134.3,131.2,128.8,128.1,127.9,126.2,1
实施例19:苯基(2-苯基-1H-吡咯-3-基)甲酮2s的合成,其结构式具体如下:
将1mmol烯胺酯1s和1.2mmol 2-碘酰基苯甲酸(IBX)加入到4mL四氢呋喃中,在120℃下回流反应12h。反应结束后,在反应液中加入乙酸乙酯(10mL)和水(20mL),萃取,有机相备用,水相用再用乙酸乙酯(10mL)萃取两次,然后合并3次有机相,无水硫酸钠干燥,过滤后减压浓缩,所得粗产品快速硅胶柱层析(V乙酸乙酯∶V石油醚=1∶3),纯化得到产品,产率45%。其主要理化性质如下:
1H NMR(400MHz,CDCl3):δ 8.87(s,1H),7.76-7.78(m,2H),7.40-7.43(m,3H),7.29-7.33(m,2H),7.23-7.27(m,3H),6.76-6.77(m,1H),6.58-6.59(m,1H).13C NMR(100MHz,CDCl3):δ 192.8,139.7,137.3,132.2,131.1,129.8,128.6,128.5,128.1,128.0,120.5,117.9,113.8.HRMS(ESI):m/z calcd for C17H13NNaO[M+Na]+270.0889,found:270.0885。
Claims (10)
1.一种2-芳基-3-酯基多取代吡咯类化合物,其结构通式如下:
其中R1=芳基或杂环基,R2=酯基或氰基。
2.根据权利要求1所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,R1中所述芳基选自C6~C10芳基。
3.根据权利要求2所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,R1中所述芳基被1~2个烷基、烷氧基、卤素或苯基取代,所述杂环基为噻吩基。
4.根据权利要求3所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,R1中所述烷基、烷氧基的碳原子数为1~2。
5.根据权利要求1所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,R2中所述酯基为-CO2R,R为C1~C4烷烃基或C6~C10芳基。
6.根据权利要求5所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,R2中所述酯基为-CO2R,R为C1~C2烷烃基或苯基。
7.根据权利要求1所述2-芳基-3-酯基多取代吡咯类化合物,其特征在于,该类化合物选自如下的任一种:
8.一种根据权利要求1-7任一项所述的2-芳基-3-酯基多取代吡咯类化合物的合成方法,其特征在于,该方法以烯胺酯类化合物为原料,2-碘酰基苯甲酸为氧化剂,反应式如下:
9.根据权利要求8所述2-芳基-3-酯基多取代吡咯类化合物的合成方法,其特征在于,所述反应在空气环境中进行,具体是将烯胺酯类化合物溶解于四氢呋喃中,然后加入2-碘酰基苯甲酸,烯胺酯类化合物与2-碘酰基苯甲酸的摩尔比为1:(1.0~1.5),110~130℃回流反应8~16小时,得到2-芳基-3-酯基多取代吡咯类化合物的粗产物。
10.一种2-芳基-3-酯基多取代吡咯类化合物的精制方法,其特征在于,该方法包括将权利要求8反应所得2-芳基-3-酯基多取代吡咯类化合物的粗产物中加入乙酸乙酯和水,萃取,有机相备用,水相用再用乙酸乙酯萃取1~3次,然后合并有机相,无水硫酸钠干燥,过滤后减压浓缩,硅胶柱层析纯化,洗脱液是体积比为(2.8-3.2):1的石油醚-乙酸乙酯,得到2-芳基-3-酯基多取代吡咯类化合物纯品。
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