CN111440091A - 一种(e)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法 - Google Patents
一种(e)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法 Download PDFInfo
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- CN111440091A CN111440091A CN202010381409.8A CN202010381409A CN111440091A CN 111440091 A CN111440091 A CN 111440091A CN 202010381409 A CN202010381409 A CN 202010381409A CN 111440091 A CN111440091 A CN 111440091A
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- aryl
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- enenitrile
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- -1 aromatic olefin compounds Chemical class 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种(E)‑2,2‑二甲基‑4‑芳基‑丁‑3‑烯腈类化合物的合成方法，该方法是将芳香烯烃类化合物与AIBN在单质碘催化下一锅反应，得到(E)‑2,2‑二甲基‑4‑芳基‑丁‑3‑烯腈类化合物。该方法无需采用金属催化剂及有毒溶剂，有利于环保，且反应条件温和，步骤简单，目标产物收率高，原子利用率高，有利于工业化生产。
Description
技术领域
本发明涉及一种烯腈类化合物的合成方法，特别涉及一种通过芳香烯烃类化合物与偶氮二异丁腈在碘催化作用下通过直接交叉偶联获得(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的方法，属于有机合成领域。
背景技术
丙烯腈类化合物是一种广泛存在于药物产品中的重要化合物，例如维生素D受体，农药和抗HIV药物等。此外，由于丙稀晴类化合物中的氰基可以通过加成、水解、还原等化学反应很容易转化为胺、酰胺和羧酸等官能基团，因此，丙稀晴类化合物等含氰基(CN)的化合物已被广泛用于引入胺、酰胺和羧酸等修饰功能基团的通用中间体。因此，化学家对丙烯腈类化合物的关注度仍然很高。
在过去的几十年中，人们一直致力于合成丙烯腈类化合物。在早期的合成丙稀晴类化合物的方法中，主要选择带有良好离去基团的底物来合成丙稀晴类化合物，例如卤化物、羟基或乙酸酯等，这些底物用于与腈源偶合以合成丙烯腈类化合物([1]R.Yoneda,S.Harusawa and T.Kurihara,J.Org.Chem.,1991,56,1827.[2]M.Rad,A.Khalafi-Nezhad,S.Behrouz and M.Faghihi,Tetrahedron Lett.2007,48,6779.[3]F.Teng,J.-T.Yu,Y.Jiang,H.Yang and J.Cheng,Chem.Commun.,2014,50,8412.[4](a)D.Munemori,H.Tsuji,K.Uchida,T.Suzuki,K.Isa,M.Minakawa and M.Kawatsura,Synthesis,2014,46,2747.[5]J.Wang,Y.Masui and M.Onaka,ACS Catal.,2011,1,446.[6]Y.Tsuji,T.Kusui,T.Kojima,Y.Sugiura,N.Yamada,S.Tanaka,M.Ebihara and T.Kawamura,Organometallics,1998,17,4835；[7]Y.Tsuji,N.Yamada and S.Tanaka,J.Org Chem.,1993,58,16.)。
但是，这些方法大多采用氰化物MCN(M＝Li，Na，Cu)作为腈化试剂不是理想的选择，因为它们具有高毒性(如1a)。在最近报道的合成方法中，通过使用偶氮二腈化合物作为腈化试剂来替代早期的腈化试剂来合成丙烯腈类化合物，例如AIBN(2,2'-Azobis(2-methylpropionitrile))和ACCN(1,1'-azobis(环己烷-1-甲腈)是新报道的氰化试剂，如([8]F.Teng,J.-T.Yu,Z.Zhou,H.Chu and J.Cheng,J.Org Chem.,2015,80,2822.[9]F.Teng,J.-T.Yu,H.Yang,Y.Jiang and J.Cheng,Chem.Commun.,2014,50,12139.[10]X.-W.Lan,N.-X.Wang,C.-B.Bai,C.-L.Lan,T.Zhang,S.-L.Chen and Y.Xing,Org.Lett.,2016,18,5986.[11]W.Wei,J.Wen,D.Yang,M.Guo,L.Tian,J.You and H.Wang,RSC Adv.,2014,4,48535.[12]G.Rong,D.Liu,H.Yan,J.Chen,Y.Zheng,G.Zhang and J.Mao,Adv.Synth.Catal.,2015,357,71.[13]H.Xu,P.-T.Liu,Y.-H.Li and F.-S.Han,Org.Lett.,2013,15,3354.[14]Y.Xie,S.Guo,L.Wu,C.Xia and H.Huang,Angew.Chem.Int.Ed.,2015,54,5900.[15]R.Wang and W.Bao,RSC Adv.,2015,5,57469.)。Mao和Mi分别报道了炔基与AIBN的铜催化氰化反应，通过Csp-Csp键的加成氰化反应合成丙烯腈类化合物(如1b)，如((a)G.Rong,J.Mao,Y.Zheng,R.Yao and X.Xu,Chem.Commun.,2015,51,13822；(b)C.Huang,G.Li,L.Zhang,Y.Zhang,L.Mi and H.Hou,Chem.Eur.J.,2019,25,10366.)。Huang的研究小组开发了在CuBr2和AgOAc存在的情况下肉桂酸和ACCN的脱羧交叉偶联反应，从而获得了这些不饱和腈(如1c)，如(B.Gao,Y.Xie,L.Yang andH.Huang,Org.Biomol.Chem.,2016,14,2399.)。在2017年，Lee等人最新提出了铜或胺催化的方法，通过炔基羧酸的脱羧及与偶氮二异丁腈反应选择性合成(E)-或(Z)-烯丙基腈(如1d)(F.Irudayanathan and S.Lee,Org.Lett.,2017,19,2318.)。最近报道的这些合成丙烯腈类化合物的方法已经取得了明显的进展，避免了使用有毒的氰化物，并且以较高产率获得了许多芳族丙烯腈。然而，这些基于偶氮二腈的反应主要依赖于金属盐催化，并且反应中的溶剂(例如吡啶或二甲苯等)对环境不友好，且产物收率也并不高，原子利用率较低，由此，炔烃的金属催化加成氰化及不饱和酸脱羧氰化均不是丙烯腈类化合物合成的理想选择。
发明内容
针对现有技术中丙烯酸类化合物或炔基羧酸化合物的脱羧反应以及与偶氮二腈化合物的氰化反应合成丙稀腈类化合物存在的技术问题，本发明的目的是在于提供一种通过芳香烯烃类化合物与偶氮二异丁腈在碘催化作用下通过直接交叉偶联获得(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的方法，该方法无需采用金属催化剂及有毒溶剂，有利于环保，且反应条件温和，步骤简单，目标产物收率高，原子利用率高，有利于工业化生产。
为了实现上述技术目的，本发明提供了一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，该方法是将芳香烯烃类化合物与AIBN在单质碘催化下一锅反应，得到(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物；
所述芳香烯烃类化合物具有式1结构：
所述(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物具有式2结构：
其中，
Ar选自芳基或芳杂环基；
R1选自氢或烷基。
优选的方案，所述芳基选自苯基、含取代基的苯基或萘基；所述芳杂环基选自噻吩基、呋喃基、吡啶基或吡咯基。较优选的方案，所述含取代基的苯基包含至少一个取代基，所述取代基为C1～C10烷基、卤素取代基或C1～C10的烷氧基。
优选的方案，R1选择烷基时，R1选自C1～C5的烷基。
本发明的芳香烯烃类化合物中与烯烃相连的主要是芳基或芳杂环，芳基和芳杂环由于具有共轭大π键，可以提高烯烃上氢的反应活性，因此芳香烯烃类化合物相对一般的烷基烯烃类化合物在与AIBN交叉偶联过程中表现出更高的反应活性。而关于芳香烯烃类化合物中芳基上的取代基对交叉偶联存在一定影响，由于芳香烯烃与AIBN之间的交叉偶联反应主要是自由基取代反应，而有利于自由基亲核的取代基均有利于提高反应收率。本发明的芳香烯烃类化合物中芳基可以选自苯基、含取代基的苯基或萘基。含取代基的苯基包含至少一个常见的取代基，取代基的位置不限，可以为苯环的任意位置，但最好是在对位。取代基可以是卤素，具体如氟、氯或溴；取代基可以是烷基，烷基为C1～C10烷基，优选为短链烷基如C1～C5的烷基，烷基可以为直链烷基或者为带支链的烷基；取代基也可以为烷氧基，如C1～C10的烷氧基，更优选为C1～C5的烷氧基，烷氧基上的烷基可以为直链或带支链的烷基。本发明的芳香烯烃类化合物中R1取代基团可以为烷基也可以为氢，R1选自烷基时，可以为短链烷基如C1～C5的烷基，可以为直链烷基或带支链的烷基，但是R1不能选择芳基，如为苯环时，得到的是顺式的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物。
优选的方案，芳香烯烃类化合物与AIBN的摩尔比为1:1～1.5；最优选为1:1.1～1.3。
优选的方案，单质碘的摩尔量为芳香烯烃类化合物摩尔量的20～60％。最优选为芳香烯烃类化合物摩尔量的30～50％。
优选的方案，所述反应在由乙腈、二甲基亚砜、四氢呋喃、苯、水中至少一种组成的溶剂体系中进行。最优选的方案，反应在二甲基亚砜溶剂体系中进行。反应溶剂的选择较广，在综合考虑环保及收率后，最佳的溶剂为二甲基亚砜。
优选的方案，所述反应条件为：在氮气保护下，于60～120℃温度下反应2～10小时。较优选的反应条件为：在氮气保护下，于70～90℃温度下反应4～8小时。
本发明的芳香烯烃类化合物与AIBN的反应主要为自由基反应机理，以下采用苯乙烯为例进行具体说明，具体反应式如下反应式。具体反应机理为：AIBN在加热条件下，热解为异丁腈自由基，异丁腈自由基进攻苯乙烯的烯基，获得中间体M，中间体M经过自由基重排反应，并在单质碘作用下脱去氢自由基，转化成(E)-2,2-二甲基-4-芳基-丁-3-烯腈。
相对现有技术，本发明的技术方案带来的有益技术效果：
1、本发明的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物合成方法无需采用过渡金属或贵金属等催化剂，在单质碘作用下即可促进交叉偶联反应进行，不但降低催化剂成本，同时避免金属催化剂废液的产生，有利于环保。
2、本发明的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物合成方法反应条件温和，步骤简单，通过在较低的温度条件下通过一锅法实现，有利于工业化生产。
3、本发明的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物合成方法可以获得高选择性反式产物，且产物收率较高，原子利用率高。
4、本发明的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物合成方法可以采用常见的有机溶剂或水来实现，避免了有毒溶剂的使用。
附图说明
图1为实施例1的(E)-2,2-dimethyl-4-phenylbut-3-enenitrile核磁氢谱图；
图2为实施例1的(E)-2,2-dimethyl-4-phenylbut-3-enenitrile核磁碳谱图；
图3为实施例2的(E)-2,2-dimethyl-4-(p-tolyl)but-3-enenitrile核磁氢谱图；
图4为实施例2的(E)-2,2-dimethyl-4-(p-tolyl)but-3-enenitrile核磁碳谱图；
图5为实施例17的(E)-2,2,3-trimethyl-4-phenylbut-3-enenitrile核磁氢谱图；
图6为实施例17的(E)-2,2,3-trimethyl-4-phenylbut-3-enenitrile核磁碳谱图。
具体实施方式
以下具体实施例旨在进一步说明本发明内容，而不是限制本发明权利要求的保护范围。
除非另有说明，以下实施例中所有溶剂和反应物均购自商业来源，无需进一步纯化即可使用。
所有目标化合物均根据NMR(1H和13C)光谱数据表征。
NMR测量在Bruker AV400 MHz上进行，数据以相对于三甲基硅烷(ppm＝0)的ppm记录，并相对于氘代氯仿的信号(1H为7.26ppm，13C为77.00ppm)进行测量。
GC-MS分析采用Shimadzu GC-MS(QP-2010)。
反应在带螺纹末端的密封管(25ml)中进行。
溶剂(DMSO)采用活化分子筛处理。
条件优化实验：
在密封管中加入DMSO(3mL)，然后在同一管中引入芳香烯烃类化合物(0.5mmol)，AIBN(0.6mmol)和I2(0～60mol％)。将N2引入试管2分钟后，将试管的螺纹端密封，并在室温～120℃的油浴中加热6小时。当反应完成时，将管冷却至室温。将反应混合物用3mL EA稀释，并将Na2S2O3加入混合物中以除去I2。然后，将混合物洗涤并用H2O(饱和NaCl)和EA萃取两次。最后，萃取液用旋转蒸发仪浓缩，并通过柱色谱法纯化，使用硅胶(200-300目大小)，用石油醚(PE)/乙酸乙酯(EA)作为洗脱剂。最终得到目标产物。
本发明以苯乙烯(1a)和AIBN(2a)为底物合成3aa(实验结果列于表1)为例，为腈化反应寻求最佳条件。从表1中可以看出在无催化剂的条件下不能获得所需的产物3aa(条目1)。本发明研究了不同类型的碘化物催化剂，KI和TBAI均未以令人满意的产率提供所需的产物3aa(表1的条目2和3)。值得注意的是，1当量的1a和1.2当量的2a与40mol％的I2可以在DMSO溶剂中于80℃在N2中反应6h，以最佳收率88％获得所需化合物3aa(条目4)。当I2的负载降低到20mol％或增加到60mol％时，获得了较低的产率(条目5和6)。同样，减少或增加AIBN(2a)的用量都不会对产量产生较大的负面影响(条目7和8)。溶剂的性质将直接影响反应，MeCN、THF、苯和H2O能够获得反应产物，但并不能获得高产率，而经过不同配比下的DMSO/H2O混合溶剂获得最高产率也不超过55％(条目9至13)。然后，在不同温度下进行了反应，结果表明，较低的温度(例如r.t.和60℃)或较高的温度(例如100℃和120℃)都不能提供比80℃更高的产率(条目14至17)。该反应还可以在不同的气氛中进行，在该气氛中，空气和氧气可以分别提供75％和66％收率的3aa(条目18和19)。
通过上述实验，可以确定最佳的反应条件，以下通过实施例来考察含不同取代基的芳香烯烃与AIBN的交叉偶联反应：
在密封管中加入DMSO(3mL)，然后在同一管中引入芳香烯烃(0.5mmol)，AIBN(1.2当量，0.6mmol)和I2(40mol％，50mg)。将N2引入试管2分钟后，将试管的螺纹端密封，并在80℃的油浴中加热6小时。当反应完成时，将管冷却至室温。将反应混合物用3mL EA稀释，并将Na2S2O3加入混合物中以除去I2。然后，将混合物洗涤并用H2O(饱和NaCl)和EA萃取两次。最后，萃取液用旋转蒸发仪浓缩，并通过柱色谱法纯化，使用硅胶(200-300目大小)，用石油醚(PE)/乙酸乙酯(EA)作为洗脱剂。
实施例1
原料：苯乙烯；
产物：(E)-2,2-dimethyl-4-phenylbut-3-enenitrile
洗脱剂PE/EA＝80:1。获得黄色油状液体产物72mg，产率85％。
1H NMR(400MHz,CDCl3)δ7.27(d,J＝7.2Hz,1H),7.22(t,J＝7.0Hz,2H),7.16(d,J＝6.4Hz,1H),6.65(d,J＝15.9Hz,1H),5.92(d,J＝15.9Hz,1H),1.42(s,6H).13C NMR(101MHz,CDCl3)δ135.65,130.29,129.74,128.59,128.05,126.47,123.33,34.82,27.56.m/z＝171.
实施例2
原料：4-甲基苯乙烯；
产物：(E)-2,2-dimethyl-4-(p-tolyl)but-3-enenitrile
洗脱剂PE/EA＝80:1。获得亮黄色油状液体产物79mg，产率86％。
1H NMR(400MHz,CDCl3)δ7.27(d,J＝7.2Hz,2H),7.13(d,J＝7.4Hz,2H),6.71(d,J＝15.8Hz,1H),5.97(d,J＝15.9Hz,1H),2.33(s,3H),1.52(s,6H).13C NMR(101MHz,CDCl3)δ138.00,132.92,129.64,129.34,129.32,126.41,123.52,34.83,27.67,21.17.m/z＝185.
实施例3
原料：4-异丁基苯乙烯；
产物：(E)-4-(4-(tert-butyl)phenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得桔色油状液体产物103mg，产率91％。
1H NMR(400MHz,CDCl3)δ7.34(q,J＝7.9Hz,4H),6.74(d,J＝15.9Hz,1H),5.99(d,J＝15.9Hz,1H),1.54(s,6H),1.32(s,9H).13C NMR(101MHz,CDCl3)δ151.33,132.94,129.61,129.52,126.26,125.61,123.54,34.89,34.60,31.23,27.72.m/z＝227.
实施例4
原料：4-甲氧基苯乙烯；
产物：(E)-4-(4-methoxyphenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝40:1。获得黄色油状液体产物85mg，产率85％。
1H NMR(400MHz,CDCl3)δ7.27(d,J＝7.7Hz,2H),6.82(d,J＝7.7Hz,2H),6.65(d,J＝15.9Hz,1H),5.86(d,J＝15.9Hz,1H),3.74(s,3H),1.47(s,6H).13C NMR(101MHz,CDCl3)δ159.36,128.96,128.20,127.98,127.56,123.41,113.85,55.01,34.59,27.48.m/z＝201.
实施例5
原料：4-氟苯乙烯；
产物：(E)-4-(4-fluorophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得亮黄色油状液体产物81mg，产率86％。
1H NMR(400MHz,CDCl3)δ7.25(t,J＝5.9Hz,2H),6.92(t,J＝7.9Hz,2H),6.62(d,J＝15.9Hz,1H),5.85(d,J＝15.9Hz,1H),1.43(s,6H).13C NMR(101MHz,CDCl3)δ162.44(d,J＝247.6Hz),131.81(d,J＝3.2Hz),130.08(d,J＝2.0Hz),128.56,128.04(d,J＝8.1Hz),123.25,115.50(d,J＝21.7Hz),34.78,27.50.m/z＝189.
实施例6
原料：4-氯苯乙烯；
产物：(E)-4-(4-chlorophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得淡黄色油状液体产物92mg，产率90％。
1H NMR(400MHz,CDCl3)δ7.28(s,4H),6.70(d,J＝15.9Hz,1H),6.00(d,J＝15.9Hz,1H),1.52(s,6H).13C NMR(101MHz,CDCl3)δ134.12,133.62,130.92,128.70,128.53,127.67,123.11,34.81,27.44.m/z＝205.
实施例7
原料：3-甲基苯乙烯；
产物：(E)-2,2-dimethyl-4-(m-tolyl)but-3-enenitrile
洗脱剂PE/EA＝80:1。获得亮黄色油状液体产物77mg，产率83％。
1H NMR(400MHz,CDCl3)δ7.28–7.16(m,3H),7.11(d,J＝7.0Hz,1H),6.75(d,J＝15.9Hz,1H),6.04(d,J＝15.9Hz,1H),2.37(s,3H),1.55(s,6H).13C NMR(101MHz,CDCl3)δ138.15,135.57,130.07,129.78,128.82,128.48,127.14,123.63,123.37,34.80,27.56,21.25.m/z＝185.
实施例8
原料：3-氟苯乙烯；
产物：(E)-4-(3-fluorophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得亮黄色油状液体产物75mg，产率80％。
1H NMR(400MHz,CDCl3)δ7.29(dd,J＝16.4,9.2Hz,1H),7.14(d,J＝7.7Hz,1H),7.09(d,J＝10.0Hz,1H),6.97(t,J＝8.1Hz,1H),6.73(d,J＝15.9Hz,1H),6.04(d,J＝15.9Hz,1H),1.55(s,1H).13C NMR(101MHz,CDCl3)δ163.06(d,J＝245.9Hz),138.05,131.78,130.17(d,J＝8.4Hz),128.90(d,J＝2.5Hz),123.15,122.57(d,J＝2.7Hz),114.98(d,J＝21.4Hz),112.99(d,J＝22.0Hz),34.94,27.60.m/z＝189.
实施例9
原料：3-氯苯乙烯；
产物：(E)-4-(3-chlorophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得黄色油状液体产物84mg，产率82％。
1H NMR(400MHz,CDCl3)δ7.26(s,1H),7.13(s,3H),6.59(d,J＝15.9Hz,1H),5.92(d,J＝15.9Hz,1H),1.42(s,6H).13C NMR(101MHz,CDCl3)δ137.53,134.55,131.81,129.86,128.56,128.02,126.29,124.90,123.07,34.91,27.50n.m/z＝205.
实施例10
原料：2-氯苯乙烯；
产物：(E)-4-(2-chlorophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得黄色油状液体产物85mg，产率83％。
1H NMR(400MHz,CDCl3)δ7.48(d,J＝6.7Hz,1H),7.37(d,J＝6.8Hz,1H),7.28–7.19(m,2H),7.13(d,J＝15.9Hz,1H),6.05(d,J＝15.9Hz,1H),1.57(s,6H).13C NMR(101MHz,CDCl3)δ133.99,133.34,133.15,129.78,129.12,126.95,126.87,126.42,123.19,34.90,27.41.m/z＝205.
实施例11
原料：2-溴苯乙烯；
产物：(E)-4-(2-bromophenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝80:1。获得桔色油状液体产物96mg，产率77％。
1H NMR(400MHz,CDCl3)δ7.56(d,J＝7.8Hz,1H),7.46(d,J＝7.6Hz,1H),7.28(t,J＝7.5Hz,1H),7.17–7.10(m,2H),6.00(d,J＝15.8Hz,1H),1.57(s,6H).13C NMR(101MHz,CDCl3)δ135.77,133.29,132.99,129.35,129.06,127.50,127.14,123.79,123.17,34.81,27.38.m/z＝249.
实施例12
原料：2-萘乙烯；
产物：(E)-2,2-dimethyl-4-(naphthalen-2-yl)but-3-enenitrile
洗脱剂PE/EA＝80:1。获得黄色油状液体产物81mg，产率73％。
1H NMR(400MHz,CDCl3)δ7.86–7.79(m,3H),7.78(s,1H),7.57(d,J＝8.5Hz,1H),7.51–7.45(m,2H),6.93(d,J＝15.9Hz,1H),6.16(d,J＝15.9Hz,1H),1.59(s,6H).13C NMR(101MHz,CDCl3)δ133.48,133.16,130.67,129.99,128.35,128.02,127.64,126.86,126.41,126.16,123.44,123.33,35.02,27.73.m/z＝221.
实施例13
原料：2-乙基苯乙烯；
产物：(E)-4-(2-ethylphenyl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝100:1。获得深橙色油状液体产物33mg，产率33％。
1H NMR(400MHz,CDCl3)δ7.34–7.27(m,1H),7.27–7.18(m,2H),7.12(d,J＝6.9Hz,1H),6.75(d,J＝15.9Hz,1H),6.03(d,J＝15.9Hz,1H),2.65(q,J＝7.5Hz,2H),1.55(s,6H),1.25(t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ144.66,135.74,130.12,130.02,128.63,128.16,127.76,126.12,123.90,34.88,28.77,27.68,15.53.m/z＝199.
实施例14
原料：2-呋喃基乙烯；
产物：(E)-4-(furan-2-yl)-2,2-dimethylbut-3-enenitrile
洗脱剂PE/EA＝60:1。获得深黄色油状液体产物51mg，产率63％。
1H NMR(400MHz,CDCl3)δ7.36(s,1H),6.57(d,J＝15.9Hz,1H),6.39(s,1H),6.00(d,J＝15.8Hz,1H),1.52(s,6H).13C NMR(101MHz,CDCl3)δ142.38(s),128.86(s),118.32(s),111.46(s),109.24(s),34.82(s),27.66(s).m/z＝161.
实施例15
原料：2-噻吩基乙烯；
产物：(E)-2,2-dimethyl-4-(thiophen-2-yl)but-3-enenitrile
洗脱剂PE/EA＝60:1。获得深黄色油状液体产物60mg，产率68％。
1H NMR(400MHz,CDCl3)δ7.19(d,J＝4.9Hz,1H),7.04–6.95(m,2H),6.89(d,J＝15.7Hz,1H),5.88(d,J＝15.7Hz,1H)1.53(s,6H).13C NMR(101MHz,CDCl3)δ140.52,129.69,127.47,126.69,124.82,123.25,123.18,34.80,27.62.m/z＝177.
实施例16
原料：2-吡啶基乙烯；
产物：(E)-2,2-dimethyl-4-(pyridin-2-yl)but-3-enenitrile
洗脱剂PE/EA＝1:1。获得桔黄色油状液体产物60mg，产率68％。
1H NMR(400MHz,CDCl3)δ8.57(s,1H),7.67-7.70(m,1H),7.26(d,J＝4.0Hz,1H),7.23-7.15(m,1H),6.83(d,J＝15.6,1H),6.70(d,J＝15.6,1H),1.58(s,6H).13C NMR(101MHz,CDCl3)δ153.85,149.46,136.99,135.03,129.07,123.17,122.85,122.80,35.00,27.55).m/z＝172.
实施例17
原料：(E)-β-甲基苯乙烯；
产物：(E)-2,2,3-trimethyl-4-phenylbut-3-enenitrile
洗脱剂PE/EA＝100:1。获得亮黄色油状液体产物54mg，产率58％。
1H NMR(400MHz,CDCl3)δ7.35(t,J＝7.5Hz,2H),7.23(d,J＝7.8Hz,3H),6.72(s,1H),1.93(s,3H),1.59(s,6H).13C NMR(101MHz,CDCl3)δ137.08,136.89,128.97,128.17,126.84,126.06,124.19,39.24,26.39,14.22.m/z＝185.
实施例18
原料：(E)-1,2-二苯乙烯；
产物：(Z)-2,2-dimethyl-3,4-diphenylbut-3-enenitrile(4b)
洗脱剂PE/EA＝70:1。获得黄色油状液体产物65mg，产率53％。
1H NMR(400MHz,CDCl3)δ7.40–7.36(m,3H),7.20–7.12(m,2H),7.08(d,J＝4.4Hz,3H),6.97(s,1H),6.87–6.79(m,2H),1.55(s,6H).13C NMR(101MHz,CDCl3)δ141.10,136.53,135.66,130.12,129.26,128.73,128.43,127.94,127.26,126.16,124.13,39.32,27.18.m/z＝247.
该实施例可以看出，当与烯烃β位连接基团为芳基时，产物为顺式产物。
实施例19
原料：十四碳烯；
产物：2,2-dimethylhexadec-3-enenitrile
洗脱剂PE/EA＝60:1。获得橙色油状液体产物43mg，产率33％。
1H NMR(400MHz,CDCl3)δ5.82(m,1H),5.31(d,J＝15.5Hz,1H),2.32–1.94(m,2H),1.37(m,6H),1.33–1.19(m,20H),0.88(t,J＝5.9Hz,3H).13C NMR(101MHz,CDCl3)δ136.39,130.98,123.38,43.98,34.39,32.53,31.90,29.63,29.45,29.42,29.33,29.13,29.07,28.96,27.70,26.25,22.67,14.09.m/z＝263.
该实施例可以看出，当与烯烃连接基团为烷基时，产物的收率相对较低。
以上实施例中获得的(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物可以通过现有技术常见的方法进一步转化成酰胺类化合物：3aa(0.5mmol)，并在引入2ml DMF的管中加入。然后，在同一管中加入2.0当量的K2CO3和10.0当量的H2O2。反应在60℃下进行36小时，并通过TLC和GC-MS进行监测。反应完成后，将混合物冷却至室温并洗涤，并用H2O(饱和NaCl)和EA萃取。最后，萃取液用旋转蒸发仪浓缩，并通过柱色谱法纯化，使用硅胶(200-300目大小)，用石油醚(PE)/乙酸乙酯(EA)作为洗脱剂。
Claims (9)
1.一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：将芳香烯烃类化合物与AIBN在单质碘催化下一锅反应，得到(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物；
所述芳香烯烃类化合物具有式1结构：
所述(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物具有式2结构：
其中，
Ar选自芳基或芳杂环基；
R1选自氢或烷基。
2.根据权利要求1所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：
所述芳基选自苯基、含取代基的苯基或萘基；
所述芳杂环基选自噻吩基、呋喃基、吡啶基或吡咯基。
3.根据权利要求2所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述含取代基的苯基包含至少一个取代基，所述取代基为C1～C10烷基、卤素取代基或C1～C10的烷氧基。
4.根据权利要求1所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述烷基选自C1～C5的烷基。
5.根据权利要求1所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：
芳香烯烃类化合物与AIBN的摩尔比为1:1～1.5；
单质碘的摩尔量为芳香烯烃类化合物摩尔量的20～60％。
6.根据权利要求1所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述反应在由乙腈、二甲基亚砜、四氢呋喃、苯、水中至少一种组成的溶剂体系中进行。
7.根据权利要求6所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述反应在二甲基亚砜溶剂体系中进行。
8.根据权利要求1～7任一项所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述反应条件为：在氮气保护下，于60～120℃温度下反应2～10小时。
9.根据权利要求8所述的一种(E)-2,2-二甲基-4-芳基-丁-3-烯腈类化合物的合成方法，其特征在于：所述反应条件为：在氮气保护下，于70～90℃温度下反应4～8小时。
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