CN107673997A - 2,3‑二取代环丙烷‑1‑甲腈 - Google Patents

2,3‑二取代环丙烷‑1‑甲腈 Download PDF

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CN107673997A
CN107673997A CN201710968535.1A CN201710968535A CN107673997A CN 107673997 A CN107673997 A CN 107673997A CN 201710968535 A CN201710968535 A CN 201710968535A CN 107673997 A CN107673997 A CN 107673997A
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cyclopropane
organic phase
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2mmol
hexanes
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卞小琴
王立中
马永刚
王存德
王婷
代晨路
叶伟建
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Yangzhou University
Taizhou Polytechnic College
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Taizhou Polytechnic College
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Abstract

本发明涉及一种2,3‑二取代环丙烷‑1‑甲腈，其结构式如下：其中，R1、R2对应于下表的一种：具体为如下10个化合物：

Description

2,3-二取代环丙烷-1-甲腈
技术领域
本发明属于化学合成领域，涉及到2,3-二取代环丙烷-1-甲腈，具体是2,3-二取代环丙烷-1-甲腈10个化合物。
背景技术
多取代的环丙烷是环状化合物中一类重要分支，他们的重要性一般主要在于作为天然产物的结构修饰【D.Y.K.Chen,R.H.Pouwer and J.A.Richard,Chem.Soc.Rev.2012,41,4631.Y.Li,M.Carbone,R.M.Vitale,P.Amodeo,F.Castelluccio,G.Sicilia,E.Mollo,M.Nappo,G.Cimino,Y.W.Guo and M.Gavagnin,J.Nat.Prod.,2010,73,133.】。特别是他们的生物活性，许多药学上的化合物都是以几个取代三元环作为母核【G.Nowak,L.A.Siwek,E.Niedzielska,B.Pomierny,A. andA.Pilc,Neuropharmacology,2014,84,46.A.Gagnon,M.Duplessis and L.Fader,Org.Prep.Proced.Int.,2010,42,1.】。例如，2014年1月31日，他司美琼(Figure 1)在被FDA批准的治疗盲人非24小时睡眠紊乱的药物。在他们中，1,2,3-三取代环丙烷也已经被用作潜在的选择性治疗mGluR2拮抗剂【M.Marinozzi,B.Natalini,G.Costantino,P.Tijskens,C.Thomsen and R.Pellicciari,Bioorg.Med.Chem.Lett.,1996,6,2243；N.Jullian,I.Brabet,J.P.Pin and F.C.Acher,J.Med.Chem.,1999,42,1546.】，选择性肾素抑制剂【S.F.Martin,R.E.Austin,C.J.Oalmann,W.R.Baker,S.L.Condon,E.DeLara,S.H.Rosenberg,K.P.Spina,H.H.Stein,J.Cohen and H.D.Kleinert,J.Med.Chem.,1992,35,1710.】，作为治疗亨廷顿氏病组蛋白去乙酰化酶抑制剂(HDAC)【R.W.Bürli,C.A.Luckhurst,O.Aziz,K.L.Matthews,D.Yates,K.A.Lyons,M.Beconi,G.McAllister,P.Breccia,A.J.Stott,S.D.Penrose,M.Wall,M.Lamers,P.Leonard,I.Müller,C.M.Richardson,R.Jarvis,L.Stones,S.Hughes,G.Wishart,A.F.Haughan,C.O’Connell,T.Mead,H.McNeil,J.Vann,J.Mangette,M.Maillard,V.Beaumont,I.Munoz-Sanjuan andC.Dominguez,J.Med.Chem.,2013,56,9934.】。三元环作为最重要的环状化合物之一，取代三元环作为合成中间体在有机合成方面有非常广泛的应用【C.J.Thibodeaux,W.C.Changand H.W.Liu,Chem.Rev.,2012,112,1681.D.Y.K.Chen,R.H.Pouwerb and J.A.Richardc,Chem.Soc.Rev.,2012,41,4631.G.W.Wang,N.G.McCreanor,M.H.Shaw,W.G.Whittinghamand J.F.Bower,J.Am.Chem.Soc.,2016,138,13501.】
Figure 1 1,2,3-三取代环丙烷生物活性分子例子
三元环衍生物通常通过Simmons-Smith环丙烷化反应，这是从烯烃制备多取代环丙烷的最重要的方法之一【A.B.Charette and A.Beauchemin,Org.React.,2001,58,1.】。此外还有Corey-Chaykovsky环丙烷化反应、金属催化重氮化合物与烯烃的反应、卡宾与烯烃的环化反应【R.J.Paxton and R.J.K.Taylor,Synlett,2007,633；A.Hartikka andP.I.Arvidsson,J.Org.Chem.,2007,72,5874.】。
虽然这些经典而有效合成环丙烷衍生物的方法证明是非常有效，但是，寻求有效合成多取代环丙烷仍然是合成化学家们追求的目标。近年来，许多使用Pd催化环丙烷芳基化反应成为合成各种1,2,3-三取代环丙烷的有效方法【J.M.M.Dunn,J.T.Kuethe,R.K.Orr,M.Tudge and L.C.Campeau,Org.Lett.,2014,16,6314.】。最近，Yan等人提供了一种更高效合成2-芳甲酰基-3-芳基-1-氰基环丙烷-1-羧酸酯【Q.Wang,X.Song,J.Chen and C.Yan,J.Combi.Chem.,2009,11,1007；V.Rama,K.Kanagaraj,T.Subramanian,P.Suresh andK.Pitchumani,Catal.Commun.,2012,26,39；A.E.Raveendran,R.R.Paul,E.Suresh andV.Nair,Org.Biomole.Chem.,2010,8,901.】。沿着这条思路，各种合成具有重要生物活性的1,2,3-三取代环丙烷衍生物的方法已经被报道。所有这些报道都没有研究2-芳甲酰基-3-芳基-1-氰基环丙烷-1-羧酸酯脱脂化反应(Scheme 1)。
发明内容
针对以上所述缺陷，本发明提供了一种2,3-二取代环丙烷-1-甲腈，其结构式如下：
其中，R1、R2对应于下表的一种：
其化合物有如下10个：
本发明中C2位为芳甲酰基，C3位为芳基，C1位为氰基。
采用以上技术方案后，本发明中保留了三元环活性结构单元对生物活性重要作用，脱脂化反应形成1,2,3-三取代环丙烷。
本发明2,3-二取代环丙烷-1-甲腈可以作为药物前体，作为临床药物筛选化合物，进一步研究可以与一种或多种药用辅料形成药学上可以接受的任一剂型。
具体实施方式
本发明一种2,3-二取代环丙烷-1-甲腈，其结构式如下：
其中，R1、R2对应于下表的一种：
其化合物有如下10个：
本发明中C2位为芳甲酰基，C3位为芳基，C1位为氰基。
测试仪器
红外光谱分析：Bruker tensor 27红外光谱仪，KBr压片法，检测范围为4000～400cm-1；熔点测量：WRR熔点仪(上海精密科学仪器有限公司)，数据未经校正。1H-NMR及13C-NMR分析：Bruker Advance 600(德国Bruker公司)；反应进程用TLC跟踪检测。
2,3-二取代环丙烷-1-甲腈(2a-j)的合成
Scheme 1 2,3-二取代环丙烷-1-甲腈衍生物的合成
实施例1 2-(4-溴苯甲酰基)-3-(4-甲苯基)环丙烷-1-甲腈(2a)的合成
称取2-(4-溴苯甲酰基)-3-(p-甲苯基)-1-氰基环丙烷-1-羧酸酯0.804g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率91％；m.p.151.2-151.9℃(EA/PE)；IR(KBr,cm-1):ν＝3041,2953,2917,2236,1722,1584,1491,1434,1404,1353,1266,1221,1170,1097,1015,816,529,483；1H-NMR(600MHz,CDCl3)δ(ppm):7.83(d,J＝8.4Hz,2H),7.59(d,J＝7.8Hz,2H),7.09(d,J＝7.8Hz,2H),7.00(d,J＝7.2Hz,2H),3.26(dd,J＝6.0 and 7.8Hz,1H),3.21(dd,J＝6.0 and 7.8Hz,1H),2.27(s,3H),2.26(dd,J＝6.0 and 7.8Hz,1H)；13C-NMR(CDCl3,150MHz)δ(ppm):191.8,138.1,135.4,132.4,132.2,129.9,129.7,129.3,126.5,116.6,32.3,31.0,21.1,15.9；HRMS(ESI)calcd.forC18H15BrNO[(M+H)+]:340.0332.Found:340.0324.
实施例2 2-(4-溴苯基)-3-(4-氯苯甲酰基)环丙烷-1-甲腈(2b)的合成
称取2-(4-溴苯基)-3-(4-氯苯甲酰基)-1-氰基环丙烷-1-羧酸酯0.865g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率92％；m.p.169.8-170.6℃(EA/PE)；IR(KBr,cm-1):ν＝3051,2961,2919,2240,1730,1586,1492,1437,1401,1351,1264,1223,1175,1094,1011,810,526,481；1H-NMR(400MHz,CDCl3)δ(ppm):7.91(d,J＝8.4Hz,2H),7.43(d,J＝8.4Hz,2H),7.41(d,J＝8.4Hz,2H),7.00(d,J＝8.4Hz,2H),3.27(dd,J＝6.0 and 7.2Hz,1H),3.23(dd,J＝6.0 and 7.2Hz,1H),2.28(dd,J＝6.0 and7.2Hz,1H)；13C-NMR(CDCl3,100MHz)δ(ppm):191.1,140.7,134.7,134.4,132.2,129.8,129.3,128.3,122.1,116.2,110.0,106.8,31.5,30.8,15.8；HRMS(ESI)calcd.forC17H12BrClNO[(M+H)+]:359.9785.Found:359.9778.
实施例3 2-苯甲酰基-3-(p-甲苯基)环丙烷-1-甲腈(2c)的合成
称取2-苯甲酰基-3-(p-甲苯基)-1-氰基环丙烷-1-羧酸酯0.664g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率84％；m.p.157.6-158.9℃(EA/PE)；IR(KBr,cm-1):ν＝3055,2919,2236,1667,1590,1519,1446,1401,1352,1270,1223,1034,1000,941,797,713,687,648,532；1H-NMR(400MHz,CDCl3)δ(ppm):7.97(d,J＝7.6Hz,2H),7.58(dd,J＝7.6 and 7.2Hz,1H),7.47(d,J＝7.6Hz,2H),7.20(d,J＝8.0Hz,2H),7.14(d,J＝8.0Hz,2H),3.52(dd,J＝6.0 and 5.2Hz,1H),2.95(dd,J＝6.0 and5.2Hz,1H),2.63(dd,J＝6.0 and 5.2Hz,1H),2.29(s,3H)；13C-NMR(CDCl3,100MHz)δ(ppm):192.7,138.0,136.7,133.9,132.6,129.7,128.9,128.4,126.5,116.8,32.1,31.0,21.1,15.8；HRMS(ESI)calcd.for C18H16NO[(M+H)+]:262.1226.Found:262.1222.
实施例4 2-(4-氯苯甲酰基)-3-(2-甲氧基苯基)环丙烷-1-甲腈(2d)的合成
称取2-(4-氯苯甲酰基)-3-(2-甲氧基苯基)-1-氰基环丙烷-1-羧酸酯0.767g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率82％；m.p.140.6-141.1℃(EA/PE)；IR(KBr,cm-1):ν＝3412,3054,2976,2248,1667,1605,1514,1429,1358,1266,1231,1179,1028,868,823,789,731,689,596；1H-NMR(400MHz,CDCl3)δ(ppm):7.91(d,J＝8.4Hz,2H),7.39(d,J＝8.4Hz,2H),7.21(dd,J＝8.4 and 7.6Hz,1H),7.00(d,J＝7.6Hz,1H),6.86(d,J＝7.6Hz,1H),6.81(d,J＝8.4Hz,1H),3.74(s,3H),3.30(d,J＝7.2Hz,2H),2.39(dd,J＝7.6 and 7.2Hz,1H)；13C-NMR(CDCl3,100MHz)δ(ppm):192.4,158.2,140.2,135.2,129.8,129.3,129.1,127.7,123.6,120.6,117.3,110.7,55.4,29.5,29.4,14.6；HRMS(ESI)calcd.for C18H14ClNNaO2[(M+Na)+]:334.0600.Found:334.0613.
实施例5 2-苯甲酰基-3-(3-氯苯基)环丙烷-1-甲腈(2e)的合成
称取2-苯甲酰基-3-(3-氯苯基)-1-氰基环丙烷-1-羧酸酯0.675g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率78％；m.p.144.4-145.1℃(EA/PE)；IR(KBr,cm-1):ν＝3057,2979,2244,1665,1602,1512,1427,1355,1263,1234,1176,1027,865,828,782,733,682,599；1H-NMR(600MHz,CDCl3)δ(ppm):7.98(d,J＝7.8Hz,2H),7.58(dd,J＝7.8 and 7.2Hz,1H),7.46(dd,J＝7.8 and 7.2Hz,2H),7.22(d,J＝4.2Hz,2H),7.10(s,1H),7.04(dd,J＝4.2 and 4.2Hz,1H),3.34-3.29(m,2H),2.28(dd,J＝7.8 and 7.2Hz,1H)；13C-NMR(CDCl3,150MHz)δ(ppm):192.2,137.7,136.5,135.0,134.1,130.3,129.0,128.5,128.3,126.7,125.2,116.3,31.4,30.9,15.8；HRMS(ESI)calcd.forC17H12ClNNaO[(M+Na)+]:304.0500.Found:304.0495.
实施例6 2-(4-溴苯甲酰基)-3-(3-氯苯基)环丙烷-1-甲腈(2f)的合成
称取2-(4-溴苯甲酰基)-3-(3-氯苯基)-1-氰基环丙烷-1-羧酸酯0.893g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率81％；m.p.147.6-148.3℃(EA/PE)；IR(KBr,cm-1):ν＝3051,2972,2243,1664,1605,1513,1428,1359,1268,1237,1176,1026,865,824,785,732,688,579；1H-NMR(400MHz,DMSO-d6)δ(ppm):8.21(d,J＝8.8Hz,2H),7.68(d,J＝8.4Hz,2H),7.52(s,1H),7.43-7.34(m,3H),3.99(dd,J＝6.0 and6.4Hz,1H),3.36(dd,J＝6.0 and 6.4Hz,1H),3.01(dd,J＝6.0 and 6.4Hz,1H)；13C-NMR(DMSO-d6,100MHz)δ(ppm):192.6,139.5,139.1,135.3,133.8,130.9,130.6,129.5,127.9,127.0,126.6,117.8,31.4,31.0,16.2；HRMS(ESI)calcd.for C17H12BrClNO[(M+H)+]:359.9785.Found:359.9778.
实施例7 2-(3-溴苯基)-3-(4-甲氧基苯甲酰基)环丙烷-1-甲腈(2g)的合成
称取2-(3-溴苯基)-3-(4-甲氧基苯甲酰基)-1-氰基环丙烷-1-羧酸酯0.884g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率87％；m.p.142.8-144.6℃(EA/PE)；IR(KBr,cm-1):ν＝3052,2974,2244,1656,1600,1512,1424,1353,1264,1229,1175,1021,860,824,785,736,687,591；1H-NMR(400MHz,CDCl3)δ(ppm):7.96(d,J＝8.0Hz,2H),7.36(d,J＝7.6Hz,1H),7.24(s,1H),7.15(dd,J＝8.0 and 7.6Hz,1H),7.08(d,J＝8.0Hz,1H),6.91(d,J＝8.0Hz,2H),3.82(s,3H),3.27(d,J＝7.6Hz,2H),2.24(dd,J＝7.6 and 7.2Hz,1H)；13C-NMR(CDCl3,100MHz)δ(ppm):190.4,164.3,138.2,131.1,130.9,130.5,129.5,129.4,125.7,123.0,116.6,114.1,55.6,31.1,30.6,15.5；HRMS(ESI)calcd.for C18H14BrNNaO2[(M+Na)+]:378.0100.Found:378.0095.
实施例8 2-(4-溴苯甲酰基)-3-(2-氯苯基)环丙烷-1-甲腈(2h)的合成
称取2-(4-溴苯甲酰基)-3-(2-氯苯基)-1-氰基环丙烷-1-羧酸酯0.893g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率86％；m.p.146.5-147.1℃(EA/PE)；IR(KBr,cm-1):ν＝3075,3033,2960,2243,1669,1584,1482,1425,1360,1272,1225,1179,1068,1001,826,759,456；1H-NMR(400MHz,CDCl3)δ(ppm):7.87(d,J＝8.4Hz,2H),7.61(d,J＝8.4Hz,2H),7.35(d,J＝6.8Hz,1H),7.24-7.20(m,2H),7.10(d,J＝6.0Hz,1H),3.43(dd,J＝6.0Hz and 6.4Hz,1H),3.19(dd,J＝6.0Hz and 6.4Hz,1H),2.32(dd,J＝7.2Hz and 7.2Hz,1H)；13C-NMR(CDCl3,100MHz)δ(ppm):191.6,135.7,135.3,133.4,132.2,129.9,129.6,129.4,128.2,127.2,116.5,113.7,31.1,29.8,15.0；HRMS(ESI)calcd.forC17H12BrClNO[(M+H)+]:359.9785.Found:359.9781.
实施例9 2-苯甲酰基-3-(2-硝基苯基)环丙烷-1-甲腈(2i)的合成
称取2-苯甲酰基-3-(2-硝基苯基)-1-氰基环丙烷-1-羧酸酯0.754g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体，产率79％；m.p.154.7-155.4℃(EA/PE)；IR(KBr,cm-1):ν＝3075,3034,2240,1666,1596,1524,1422,1347,1269,1229,1169,1076,1040,1001,793,739,690；1H-NMR(400MHz,CDCl3)δ(ppm):8.01(dd,J＝8.0Hzand 1.2Hz,1H),7.96(dd,J＝8.0Hz and 1.6Hz,2H),7.60(dd,J＝8.0Hz and 1.6Hz,1H),7.56(dt,J＝8.0Hz and 1.2Hz,1H),7.48-7.43(m,3H),7.35(d,J＝7.6Hz,1H),3.76(dd,J＝6.4Hz and 6.4Hz,1H),3.27(dd,J＝6.4Hz and 6.4Hz,1H),2.35(dd,J＝6.4Hz and6.4Hz,1H)；13C-NMR(CDCl3,100MHz)δ(ppm):192.0,149.6,136.4,134.0,133.8,131.0,129.9,129.4,128.9,128.4,125.4,116.3,30.5,29.6,15.0；HRMS(ESI)calcd.forC17H12N2NaO3[(M+Na)+]:315.0740.Found:315.0732.
实施例10 2-苯甲酰基-3-(2-氯苯基)环丙烷-1-甲腈(2j)的合成
称取2-苯甲酰基-3-(2-氯苯基)-1-氰基环丙烷-1-羧酸酯0.733g(2mmol)、碘510mg(2mmol)加入到2mL DMF和10mL甲苯混合液中，再加入三乙胺909mg(9mmol)，室温下搅拌15min。混合液搅拌回流18h，反应进程通过TLC(Hexanes/EtOAc,5:1)进行跟踪，待反应完全后，减压蒸去溶剂，残留物加入10mL水，CH2Cl2萃取2次，每次10mL，合并有机相，有机相依次用10mL水、10mL饱和食盐水洗涤，无水硫酸钠干燥，蒸去有机相，粗产物通过快速色谱法进行提纯(silica gel,EtOAc/hexanes,1/8)得到白色固体,产率88％；m.p.141.7-142.5℃(EA/PE)；IR(KBr,cm-1):ν＝3078,3031,2962,2243,1665,1582,1486,1428,1369,1271,1223,1172,1061,1000,824,758,453；1H-NMR(600MHz,CDCl3)δ(ppm):8.01(d,J＝7.8Hz,2H),7.58(dd,J＝7.2Hz and 7.8Hz,1H),7.46(dd,J＝7.2Hz and 7.8Hz,2H),7.36(d,J＝7.2Hz,1H),7.23-7.20(m,2H),7.11(d,J＝7.8Hz,1H),3.46(dd,J＝6.6Hz and 6.6Hz,1H),3.27(dd,J＝6.6Hz and 6.6Hz,1H),2.29(dd,J＝6.6Hz and 6.6Hz,1H)；13C-NMR(CDCl3,150MHz)δ(ppm):192.4,136.6,135.8,134.0,133.7,129.9,129.5,128.9,128.5,128.2,127.1,116.6,30.9,29.9,15.0；HRMS(ESI)calcd.for C17H12ClNNaO[(M+Na)+]:304.0500.Found:304.0493.
化合物2c、2g的晶体通过X-射线单晶衍射进行表征，晶体数据信息列于表1中。晶体结构进一步验证了目标化合物的结构，并且可以看出目标化合物为1,2,3-三取代以及存在三元环结构。
化合物2c分子结构
化合物2g的分子结构
表1化合物2c和2g的晶体参数

Claims (2)

1.一种2,3-二取代环丙烷-1-甲腈，其特征在于：其结构式如下：
其中，R1、R2对应于下表的一种：
2.根据权利要求1所述的一种2,3-二取代环丙烷-1-甲腈，其特征在于：具体
为如下10个化合物：
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Publication number Priority date Publication date Assignee Title
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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