CN110078651A - 一种新型的多取代3,3’-联吡咯化合物的制备方法 - Google Patents

一种新型的多取代3,3’-联吡咯化合物的制备方法 Download PDF

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CN110078651A
CN110078651A CN201810074328.6A CN201810074328A CN110078651A CN 110078651 A CN110078651 A CN 110078651A CN 201810074328 A CN201810074328 A CN 201810074328A CN 110078651 A CN110078651 A CN 110078651A
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严汝龙
齐振杰
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Abstract

本发明提供了一种新型的利用高炔胺为原料在比较温和的反应条件下合成多取代的3，3’‑联吡咯类化合物的方法。本发明使用高炔胺为底物，在一价或二价铜盐的催化条件下，利用二甲亚砜等为溶剂，简单直接合成了多取代的3，3’‑联吡咯类化合物。该反应还有一个显著的优点就是二甲亚砜等物质在此反应中既是溶剂又是氧化剂，避免了该反应需要额外的氧化剂，符合当前的原子经济以及绿色化学的要求。同时本发明所用原料制备简单，廉价易得,操作安全，收率高的要求，具有极大的工业化应用价值。

Description

一种新型的多取代3,3’-联吡咯化合物的制备方法
技术领域
本发明属于有机合成技术领域，具体涉及一种新型的多取代3,3’-联吡咯化合物的制备方法。
背景技术
3,3’-联吡咯化合物及其衍生物是一类重要的杂环化合物，该类化合物不仅是许多天然产物的核心结构单元，而且大多具有生物活性，在医药、农药以及生物化学、天然产物合成，药物合成，材料化学等方面有广泛的应用。此外， 3,3’-联吡咯类化合物还可以发生取代反应、氧化反应等多种化学转化，是合成芳环以及杂环化合物等的重要中间体，在有机合成中有着广泛的应用。因此3,3’- 联吡咯类化合物的合成方法研究一直是有机化学邻域研究的难点之一，直到现在，3,3’-联吡咯类化合物的合成方法依然很少。
传统的3,3’-联吡咯类化合物合成方法主要有两种:一种是对已经存在的吡咯环或呋喃环进行结构修饰；另一种则是以不同的底物来构建3,3’-联吡咯结构单元,目前已经公开的主要方法列举如下：
(1)以吡咯为底物：
Hua小组发现在以三氯化铁或铜盐作为氧化剂时，通过1,2,5-三取代的吡咯上的C-H的活化，使其自身偶联形成3,3’-联吡咯类化合物。1a Ono小组发现在NH4OAc为催化剂的条件下吡咯甲醛1与硝基乙烷发生Knoevenagel反应生成硝基乙烯基吡咯2，2再与异氰乙酸乙酯在DBU的作用下通过Barton–Zard合成法形成3,3'-联吡咯。1b Imahori小组报道以溴代吡咯在氯化铜作为催化剂的强碱条件下可以完成吡咯的二聚生成对称的3,3'联吡咯。1c
(2)以呋喃类化合物为底物：
Daniel B.Werz小组报道呋喃在Cu(I)催化下与重氮化合物发生环化异构化反应生成中间体，该中间体可以进一步转化为三元环的二酮，该二酮在伯胺、对甲苯磺酸的作用下经过一系列反应如形成亚胺、环的扩大、消除等反应得到最终产物3,3’-联吡咯类化合物。2
(3)以炔胺为底物：
Ritter小组报道了一种相对简单地合成3,3’-联吡咯类化合物的方法，他们利用炔胺在Pd/C催化下发生炔的氧化、重排以及脱氢等反应得到3,3’-联吡咯类化合物。该方法的缺陷是底物合成步骤多，条件苛刻。3
(4)以联芳酰基乙炔和1,3-二羰基化合物为底物：
Jaisankar小组发现以联芳酰基乙炔和1,3-二羰基化合物为原料，在In盐存在的条件下发生Michael亲核加成反应，经质子化可得3,3’-联吡咯类化合物。 4
(5)以羰基类化合物为底物：
1993年，R.W.DeSimonet小组发现三羰基乙烯基试剂与伯胺经过串联环化加成反应形成2-羟基-3-吡咯烷酮-2-羧酸酯的化合物，该化合物在经过脱水、重排等反应后得到产物2，2再经过羟基的甲基化、氧化偶联反应得到最终对称的联吡咯产物。5a C.M.Baldino.小组以I和II为原料发生反应生成产物III，该产物先在臭氧条件下分解，再与甲胺作用脱去水分子生成单吡咯分子，该单吡咯分子与N-溴代琥珀酰亚胺在二氯甲烷中反应生成溴代的产物，最后该溴代产物与硫酸二甲酯经还原、偶联等反应最终合成出3,3’-联吡咯类化合物IX。5b N.V. Zorina小组发现2,5-己联酮与羟胺作用能够生成酮肟2，2与乙炔在KOH-DMSO强碱性催化体系下能够发生成环反应生成含有吡咯环结构的化合物，最后再在该条件下自身成环形成3,3’-联吡咯类化合物5。5c
以1,3-二烯类化合物为底物：
T.P.Ananthanarayan小组发现经过乙醚处理的氢化钠在0℃下与含有山梨酸乙酯和对甲基磺酰甲基异腈的DMSO溶液反应，得到1,6二加成的产物(IV 中A＝H),该产物再与甲磺酰氯发生取代反应得到产物IV,产物IV、对甲基磺酰甲基异腈与含有氢化钠、双三甲基硅胺的THF溶液反应，经重结晶得到一个吡咯类产物，此联吡咯再发生Mannich反应得到产物VII，VII与碘甲烷发生碱化反应得到碘甲烷的化合物，接着再与IX反应得到含氰基的化合物，最后该化合物在甲醇水解的作用下与氢氧化锂反应得到一个不对称的3,3’-联吡咯。6a R.W. Desimonet小组发现若以上述中1和2为原料在三氯甲烷溶液中发生Diels-Alder反应生成产物3，随后该产物在Zn/HOAc条件下发生环的还原，最后再与三氟乙酸酐反应生成对称的3,3’-联吡咯。6b
以上几种方法的缺点是原料大多需要事先制备，且制备复杂，反应条件苛刻，通常需要昂贵的过渡金属及复杂的配体，成本较高，对直接生成多取代3’3- 联吡咯的反应较少，无法实现工业化应用。
发明内容
本发明所要解决的技术问题在于针对上述现有技术合成反应条件苛刻，反应步骤复杂，工业成本高等的问题，提供一种新型的多取代3,3’-联吡咯化合物的制备方法。
为解决上述技术问题，本发明采用的技术方案是：在反应器中加入具有通式I化合物，溶剂A，催化剂B，在温度为100℃～120℃的条件下搅拌反应2h～ 6h，对反应完全后的反应体系通过有机溶剂萃取和柱层析分离纯化，得到具有通式II的多取代3’3-联吡咯化合物，反应方程式如下：
方程式中：R1均选自脂肪烷基、苯基、取代苯基；R2选自苯基、取代苯基、杂环芳烃；而R3选自取代苯基。
上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述溶剂 A为二甲基亚砜，N,N-二甲基甲酰胺，N,N-二甲基乙酰胺，N-甲基吡咯烷酮，六甲基膦酰三胺，硝基甲烷等溶剂的一种或几种的混合物，并且A为本反应的氧化剂。
上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述溶剂B为氯化亚铜，氯化铜，溴化亚铜，氧化亚铜，碘化亚铜，氧化铜等一价或二价的铜盐的一种或几种混合物。
上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述通式 I的化合物和催化剂用量的摩尔比为1:(0.05～0.1)。
本发明与现有技术相比具有以下优点：
1、本发明使用DMSO等物质既作为溶剂又作为氧化剂，合成了多取代 3,3’-联吡咯化合物。
2、本发明所用原料制备简单，廉价易得,具有反应催化剂简单易得，反应条件温和，产物收率高等优点。
3、本发明具有操作安全，环境友好，符合绿色合成的要求，具有极大的实际应用价值。
下面通过实施例，对本发明技术方案做进一步的详细说明。
具体实施方式
实施例1：本实施例的制备方法包括以下步骤：
在磨口管中依次加入化合物Ia(0.30mmol)、二甲基亚砜(2mL)、CuCl(0.015mmol),并在110℃条件下搅拌反应2.5h，薄层色谱监测反应进程，直至反应完全；加水中止反应，用15mL乙酸乙酯萃取三次，合并有机相，减压蒸除乙酸乙酯，用石油醚/乙酸乙酯＝20/1的流动相经硅胶柱层析分离纯化，得到多取代3,3’-联吡咯化合物IIa，收率74％。反应方程式如下：
参考文献
1.(a)T.Yin and R.Hua.Chem.Lett.,2013,42,836-837.(b)H.Uno,Y.Kitawaki andN.Ono.Chem.Commun.,2002,116-117.(c)T.Higashino and H.Imahori.Chem. Eur.J.,2015,21,13375-13381.
2.J.Kaschel,T.F.Schneider,D.Kratzert,D.Stalke,and D.B.Werz.Angew.Chem.Int.Ed.,2012,51,11153-11156.
3.R.Gleiter and J.Ritter.Tetrahedron,1996,52,10383-10388.
4.S.Dey,C.Pal,D.Nandi,V.S.Giri,M.Zaidlewicz,M.Krzeminski,L.Smentek,B.A.Hess,J.Gawronski,M.Kwit,N.J.Babu,A.Nangia,and P.Jaisankar.Org. Lett.,2008.10,1373-1376,
5.(a)H.H.Wasserman and R.W.Desimonet.J.Am.Chem.Soc.,1993,115, 8457-8458.(b)H.H.Wasserman,V.M.Rotello,R.Frechette,Robert W.Desimone, J.U.Yoo andC.M.Baldino.Terrahedron,1997,53,8731-8738.(c)B.A.Trofimov,
A.B.Zaitsev,E.Y.Schmidt,A.M.Vasiltsov,A.I.Mikhaleva,I.A.Ushakov,A.V.Vashchenko and N.V.Zorina.Tetrahedron Letters,2004,4,3789-3791.
6.(a)P.Magnus,T.Gallagher,J.Schultz,Y.-S.Or,and T.P.Ananthanarayan.J.Am.Chem.Soc.,1987,109,2706-2711.(b)H.H.Wasserman and R.W.Desimone,J.Am.Chem.Soc.1993,115,8457-8458.
实施例1所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.23-7.20(m,4H),7.17-7.13(m,2H), 7.06-7.00(m,10H),6.89-6.87(m,4H),6.84-6.83(d,J＝4.0Hz,2H),6.12(d,J＝ 2.8Hz,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.57,132.82,130.59,130.33, 128.59,127.48,125.92,125.57,122.27,118.99,111.23；HRMS calcd for C32H25N2 [M+H]+437.2012；found:437.1993.
实施例2～31除了使用的具有通式Ia的化合物不同外，其他反应条件均相同，具体为：
在磨口管中依次加入化合物I(0.30mmol)、二甲基亚砜(2mL)、CuCl (0.015mmol),并在110℃，空气条件下搅拌反应2.5h，薄层色谱监测反应进程，直至反应完全；加水中止反应，用15mL乙酸乙酯萃取三次，合并有机相，减压蒸除乙酸乙酯，用石油醚/乙酸乙酯＝20/1的流动相经硅胶柱层析分离纯化，得到多取代3,3’-联吡咯化合物II，收率32-80％。反应方程式如下：
实施例2所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):7.17-7.09(m,8H),6.90-6.88(d,J＝8.0 Hz,6H),6.76(s,4H),6.67-6.66(d,J＝4.0Hz,2H),6.25(s,2H),1.94(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.54,138.89,138.73,132.58,132.29,129.73, 128.48,127.67,127.59,125.58,125.37,124.62,121.13,121.07,119.11,118.92, 109.38,109.24,19.97,19.80；HRMS calcd for C34H29N2[M+H]+465.2325；found: 465.2317.
实施例3所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.23-7.18(m,4H),7.15-7.11(m,2H), 7.06-7.04(d,J＝8.0Hz,4H),6.91-6.88(m,2H),6.84-6.80(m,4H),6.71-6.69(d,J ＝8.0Hz,2H),6.57(s,2H),6.18-6.17(d,J＝4.0Hz,2H),2.06(s,6H)；13C NMR (100MHz,CDCl3,ppm):δ＝140.71,136.63,132.68,131.22,130.45,128.54,127.70, 127.21,126.54,125.79,125.54,122.10,119.06,111.27,21.28；HRMS calcd for C34H29N2[M+H]+465.2325；found:465.2305.
实施例4所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.24-7.12(m,4H),7.07-7.01(m,2H), 6.93-6.87(m,8H),6.85-6.79(m,6H),6.12-6.10(m,1H),6.08-6.06(m,1H), 2.24-2.23(d,J＝4.0Hz,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.70, 135.67,130.66,130.58,130.35,130.06,128.68,128.37,127.58,125.89,125.66, 122.36,122.10,118.98,118.82,111.33,111.22,21.33；HRMS calcd for C34H29N2 [M+H]+465.2325；found:465.2339.
实施例5所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.22-7.18(m,4H),7.14-7.11(m,2H), 7.07-7.05(m,4H),6.80-6.77(m,4H),6.67-6.64(m,2H),6.59(s,2H),6.14-6.13 (d,J＝4.0Hz,2H),2.12(s,6H),1.97(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.87,135.22,133.93,131.71,130.42,130.35,128.63,128.50,128.04,125.67, 125.55,121.86,118.93,111.26,19.53,19.45；HRMS calcd for C36H33N2[M+H]+ 493.2638；found:493.2619.
实施例6所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.24-7.20(m,4H),7.16-7.14(m,2H), 7.06-7.05(d,J＝4.0Hz,2H),6.84-6.83(d,J＝4.0Hz,2H),6.78(s,2H),6.62(s,2 H),6.40(s,4H),6.21(d,J＝2.8Hz,2H),2.03(s,12H)；13C NMR(100MHz, CDCl3,ppm):δ＝140.79,136.32,132.54,130.50,128.50,128.32,127.31,125.72, 125.52,119.09,114.84,111.27,21.15；HRMS calcd for C36H33N2[M+H]+493.2638； found:493.2625.
实施例7所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.25-7.22(m,4H),7.19-7.16(m,2H), 7.06-7.04(m,4H),6.91-6.85(m,4H),6.67-6.6.63(m,2H),6.50-6.48(d,J＝8.0Hz, 2H),6.39-6.36(d,J＝12.0Hz,2H),6.30-6.29(d,J＝4.0Hz,2H)；13C NMR(100 MHz,CDCl3,ppm):δ＝163.32-160.89(d,J＝243.0Hz,1C),140.22,134.78-134.70 (d,J＝8.0Hz,1C),128.98,128.79,128.67,126.33,126.05,125.60,123.09,119.32, 116.93-116.72(d,J＝21.0Hz,1C),112.74-112.53(d,J＝21.0Hz,1C),111.43； HRMS calcd for C32H23F2N2[M+H]+473.1824；found:473.1809.
实施例8所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.24-7.20(m,4H),7.18-7.15(m,2H), 7.03-7.01(m,4H),6.88-6.87(d,J＝4.0Hz,2H),6.71-6.62(m,8H),6.25-6.24(d,J ＝4.0Hz,2H)；13CNMR(100MHz,CDCl3,ppm):δ＝162.47-160.03(d,J＝244.0 Hz,1C),140.31,131.93-131.85(d,J＝8.0Hz,1C),129.24,128.73,126.17,125.62, 122.48,118.88,114.51-114.30(d,J＝21.0Hz,1C),111.21；HRMS calcd for C32H23F2N2[M+H]+473.1824；found:473.1812.
实施例9所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.25-7.20(m,4H),7.18-7.16(m,2H), 7.04-7.02(d,J＝8.0Hz,4H),6.91-6.89(m,6H),6.62-6.60(d,J＝8.0Hz,4H), 6.29-6.28(d,J＝4.0Hz,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.21, 131.74,131.48,131.13,128.99,128.82,127.61,126.28,125.60,122.96,119.17, 111.44；HRMS calcd for C32H23Cl2N2[M+H]+505.1233；found:505.1217.
实施例10所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.47-7.45(m,4H),7.38-7.33(m,4H), 7.20-7.15(m,8H),7.00-6.99(m,2H),6.57-6.56(m,2H),6.40-6.39(m,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.39,133.64,132.71,131.25,131.02,128.91, 128.71,128.02,127.65,126.29,126.07,125.97,125.67,125.00,124.74,122.96, 112.80,109.05；HRMS calcdfor C34H23N4[M+H]+487.1917；found:487.1901.
实施例11所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.32-7.28(m,4H),7.26-7.23(m,2H), 7.21-7.19(m,4H),7.14-7.12(m,2H),6.86-6.85(d,J＝4.0Hz,2H),6.81-6.79(m, 2H),6.58-6.57(m,2H),6.17(d,J＝2.8Hz,2H)；13C NMR(100MHz,CDCl3, ppm):δ＝140.35,134.03,128.68,127.98,126.65,126.36,126.06,125.74,123.98, 122.96,120.30,111.06；HRMS calcdfor C28H21N2S2[M+H]+449.1141；found: 449.1129.
实施例12所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.01-7.99(d,J＝8.0Hz,2H), 7.82-7.80(m,2H),7.75-7.73(d,J＝8.0Hz,2H),7.44-7.31(m,6H),7.22-7.20(m, 2H),7.14-7.03(m,10H),6.49-6.48(d,J＝4.0Hz,4H)；13C NMR(100MHz, CDCl3,ppm):δ＝140.35,133.62,132.66,131.22,128.90,128.71,128.03,127.64, 126.28,126.07,125.97,125.68,125.01,124.73,122.97,112.79,109.04；HRMS calcd for C40H29N2[M+H]+537.2325；found:537.2315.
实施例13所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.84-8.82(m,2H),7.98-7.96(m,2H), 7.91-7.89(d,J＝8.0Hz,2H),7.57-7.56(d,J＝4.0Hz,2H),7.48-7.45(m,2H), 7.35-7.30(m,6H),7.22-7.19(m,4H),7.02-7.01(m,2H),6.60-6.6.59(m,2H), 7.43-6.41(m,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝150.02,146.97,140.34, 135.89,132.90,131.25,130.24,129.11,128.94,128.19,126.03,125.94,125.65, 125.20,121.34,111.70,109.54；HRMScalcd for C38H27N4[M+H]+539.2230；found: 539.2217.
实施例14所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.17-09(m,8H),6.90-6.88(d,J＝8.0 Hz,6H),6.76(s,4H),6.67-6.66(d,J＝4.0Hz,2H),6.25(s,2H),1.94(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝139.97,135.69,132.74,131.51,130.43,129.65, 128.38,127.58,127.11,126.09,125.42,122.47,117.90,110.69,17.61；HRMS calcd for C34H29N2[M+H]+465.2325；found:465.2308.
实施例15所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.07-7.01(m,8H),6.96-6.88(m,8H), 6.81(d,J＝2.8Hz,2H),6.79-6.77(d,J＝8.0Hz,2H),6.10(d,J＝2.8Hz,2H), 2.23(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝140.48,138.49,132.91,130.57, 130.27,128.25,127.40,126.59,126.07,125.84,122.78,122.21,118.91,111.13, 21.25；HRMS calcd for C34H29N2[M+H]+465.2325；found:465.2311.
实施例16所所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.03-7.00(m,10H),6.94-6.92(d,J＝ 8.0Hz,4H),6.89-6.88(m,4H),6.80-6.79(d,J＝4.0Hz,2H),6.10-6.09(d,J＝4.0 Hz,2H),2.28(s,6H)；13C NMR(100MHz,CDCl3,ppm):δ＝138.15,135.57, 132.98,130.62,130.31,129.17,127.43,125.82,125.40,122.25,118.84,111.00, 20.91；HRMS calcd for C34H29N2[M+H]+465.2325；found:465.2312.
实施例17所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.07-6.98(m,6H),6.92-6.85(m,6H), 6.80-6.78(m,2H),6.74-6.72(m,2H),6.66-6.65(m,2H),6.26(d,J＝2.8Hz,1H), 6.22(d,J＝2.8Hz,1H),2.19(s,6H),1.82-1.80(d,J＝8.0Hz,6H)；13C NMR(100 MHz,CDCl3,ppm):δ＝139.99,139.94,137.59,134.52,134.47,132.90,132.84, 131.77,131.71,129.78,129.72,129.02,128.95,127.06,126.12,126.05,125.39, 125.33,125.27,122.71,122.64,110.54,110.48,20.28,14.20,14.12；HRMS calcd for C36H33N2[M+H]+493.2638；found:493.2623.
实施例18所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.04-7.02(m,6H),6.92-6.91(m,4H), 6.80-6.78(m,4H),6.66(s,4H),6.08-6.07(m,2H),2.18(s,12H)；13C NMR(100 MHz,CDCl3,ppm):δ＝140.39,138.12,133.00,130.57,130.21,127.45,127.34, 125.78,123.33,122.15,118.81,110.97,21.15；HRMS calcd for C36H33N2[M+H]+ 493.2638；found:493.2627.
实施例19所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.04-6.94(m,14H),6.89-6.87(m,4 H),6.81-6.80(d,J＝3.0Hz,2H),6.12-6.11(d,J＝3.0Hz,2H),2.61-2.54(m,4H), 1.21-1.16(m,6H)；13C NMR(75MHz,CDCl3,ppm):δ＝141.81,138.22,132.89, 130.56,130.23,127.92,127.39,125.75,125.38,122.27,118.79,110.97,28.21,15.35； HRMS calcd for C36H33N2[M+H]+493.2638；found:493.2622.
实施例20所所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.07-7.05(d,J＝8.0Hz,4H), 7.01-6.95(m,10H),6.87-6.86(m,4H),6.82-6.81(d,J＝4.0Hz,2H),6.12-6.11(d, J＝4.0Hz,2H),2.89-2.79(m,2H),1.21-1.19(d,J＝8.0Hz,12H)；13C NMR(100 MHz,CDCl3,ppm):δ＝146.50,138.35,132.96,130.59,130.33,127.37,126.50, 125.72,125.39,122.31,118.87,111.02,33.53,23.91；HRMS calcd for C38H37N2 [M+H]+521.2951；found:521.2937.
实施例21所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.13-7.05(m,12H),6.89-6.87(m,4 H),6.85-6.83(m,2H),6.81-6.80(d,J＝4.0Hz,2H),6.10-6.09(d,J＝4.0Hz,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝141.54,134.12,132.27,130.53,130.32, 129.49,127.71,126.34,126.01,125.37,123.83,122.14,119.12,111.66；HRMS calcd for C32H23Cl2N2[M+H]+505.1233；found:505.1219.
实施例22所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.19-7.17(m,4H),7.07-7.05(m,6H), 6.98-6.96(d,J＝8.0Hz,4H),6.88-6.85(m,4H),6.79(d,J＝2.8Hz,2H),6.09(d, J＝2.8Hz,2H)；13CNMR(100MHz,CDCl3,ppm):δ＝139.04,130.59,129.15, 128.79,128.33,128.19,127.71,126.78,126.61,126.26,124.16,122.14,111.52, 111.01,109.61；HRMS calcd forC32H23Cl2N2[M+H]+505.1233；found:505.1217.
实施例23所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝2.27-7.20(m,6H),7.13-7.08(m,6H), 6.93-6.90(m,8H),6.58-6.57(d,J＝4.0Hz,2H),6.05-6.04(d,J＝4.0Hz,2H), 4.91(s,4H)；13C NMR(100MHz,CDCl3,ppm):δ＝139.24,133.04,131.03,130.59, 128.42,127.78,127.00,126.48,126.31,120.82,117.61,109.71,50.34；HRMS calcd for C34H29N2[M+H]+465.2325；found:465.2311.
实施例24所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.21-7.17(m,6H),7.01-6.99(m,4H), 6.56(d,J＝2.8Hz,2H),6.89-6.88(d,J＝4.0Hz,2H),3.67-3.64(m,4H), 1.54-1.46(m,4H),1.16-1.09(m,4H),0.78-0.74(m,6H)；13C NMR(100MHz, CDCl3,ppm):δ＝133.85,130.85,130.26,127.82,126.31,119.71,117.38,108.82, 46.65,33.43,19.77,13.60；HRMS calcd forC28H33N2[M+H]+397.2638；found: 397.2621.
实施例25所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.19-7.17(m,6H),6.93-6.91(m,4 H),6.65(d,J＝2.8Hz,2H),6.92(d,J＝2.8Hz,2H),3.66-3.60(m,2H),1.87-1.84 (d,J＝12.0Hz,4H),1.74-1.71(m,4H),1.58-1.53(m,6H),1.12(s,6H)；13C NMR (100MHz,CDCl3,ppm):δ＝133.98,130.86,129.73,127.82,126.19,116.75,115.91, 108.68,54.76,34.73,25.81,25.41；HRMS calcd for C32H37N2[M+H]+449.2951； found:449.2937.
实施例26所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.20-7.19(m,6H),7.02-6.99(m,4H), 6.56(d,J＝2.8Hz,2H),5.88-5.87(d,J＝4.0Hz,2H),3.66-3.63(m,4H), 1.53-1.49(m,4H),1.23(m,6H),1.16-1.11(m,14H),0.87-0.83(m,6H)；13C NMR (100MHz,CDCl3,ppm):δ＝133.81,130.82,130.21,127.82,126.31,119.70,117.32, 108.76,46.88,31.70,31.28,29.06,29.01,26.53,22.60,14.07；HRMS calcd for C36H49N2[M+H]+509.3890；found:509.3873.
实施例27所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.21-7.17(m,6H),7.01-6.99(m,4H), 6.56-6.55(d,J＝4.0Hz,2H),5.88(d,J＝2.8Hz,2H),3.66-3.62(m,4H), 1.56-1.41(m,4H),1.32-1.11(m,60H),0.90-0.86(m,6H)；13C NMR(100MHz, CDCl3,ppm):δ＝133.81,130.82,130.21,127.82,126.30,119.69,117.31,108.76, 46.88,31.92,31.29,29.69,29.51,29.42,29.36,29.07,26.54,22.69,14.13,1.01； HRMS calcd for C56H89N2[M+H]+789.7021；found:789.7009.
实施例28所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.35-7.32(d,J＝8.0Hz,2H), 7.17-7.10(m,10H),7.08-7.02(m,6H),6.97-6.91(m,8H),6.80-6.78(m,4H),6.66 (s,2H)；13C NMR(100MHz,CDCl3,ppm):δ＝139.14,13402,133.43,130.80, 128.86,128.52,128.39,128.35,127.78,127.43,126.50,126.24,125.80,125.36, 117.16,110.91；HRMS calcdfor C44H33N2[M+H]+589.2638；found:589.2621.
实施例29所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.27-7.23(m,6H),7.19-7.11(m,8H), 7.06-7.00(m,8H),6.98-6.96(m,4H),6.47(s,4H)；13C NMR(100MHz,CDCl3, ppm):δ＝138.72,136.24,134.50,133.05,132.13,131.74,129.76,128.89,128.85, 128.72,128.10,127.89,127.44,126.37,110.20,110.00；HRMS calcd for C44H31Cl2N2[M+H]+657.1859；found:657.1838.
实施例30所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.02-7.00(d,J＝8.0Hz,4H), 6.95-6.93(d,J＝8.0Hz,4H),6.80-6.79(d,J＝4.0Hz,2H),6.61(s,2H),6.40(s,4 H),6.19-6.18(d,J＝4.0Hz,2H),2.29(s,6H),2.03(s,12H)；13C NMR(100MHz, CDCl3,ppm):δ＝138.35,136.23,135.33,132.63,130.41,129.08,128.33,127.23, 125.29,121.97,118.85,110.92,21.18,20.91；HRMS calcd for C38H37N2[M+H]+ 521.2951；found:521.2937.
实施例31所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.22-7.20(d,J＝8.0Hz,1H), 7.17-7.12(m,2H),7.10-7.02(m,5H),6.98-6.95(m,4H),6.90-6.86(m,4H),6.73 (d,J＝2.8 Hz,2 H),5.81(d,J＝2.8 Hz,1 H),5.77-5.76(d,J＝4.0 Hz,1 H), 2.57-2.51(m,4 H),1.92(s,3 H),1.78(s,3 H),1.17-1.14(m,6 H)；13C NMR(100 MHz,CDCl3,ppm):δ＝141.45,138.95,138.79,138.25,133.57,133.46,132.62, 132.32,129.64,128.97,128.86,127.81,127.56,127.47,125.31,124.45,121.13, 121.08,118.91,118.71,109.01,108.87,28.14,20.01,19.85,15.26；HRMS calcd for C38H37N2[M+H]+521.2951；found:521.2941。

Claims (5)

1.一种新型的多取代3,3’-联吡咯化合物的制备方法，其特征在于，包括以下步骤：在反应器中加入具有通式I的化合物，溶剂A，催化剂B，在温度为90℃的条件下搅拌反应2-6h，对反应完全后的反应体系进行降温，柱层析分离纯化，得到具有通式II的多取代3,3’-联吡咯化合物，反应方程式如下：
方程式中：R1均选自脂肪烷基、苯基、取代苯基；R2选自苯基、取代苯基、杂环芳烃；而R3选自取代苯基。
2.上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述溶剂A为二甲基亚砜，N,N-二甲基甲酰胺，N,N-二甲基乙酰胺，N-甲基吡咯烷酮，六甲基膦酰三胺，硝基甲烷等溶剂的一种或几种的混合物，并且A为本反应的氧化剂。
3.上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述催化剂B为氯化亚铜，氯化铜，溴化亚铜，氧化亚铜，碘化亚铜，氧化铜等一价或二价的铜盐的一种或几种混合物。
4.上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，所述通式I的化合物和催化剂用量的摩尔比为1:(0.05～0.2)。
5.上述的一种多取代3,3’-联吡咯化合物的制备方法，其特征在于，反应温度为80℃-130℃。
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