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佘川, 余佩, 骆兴霆, 田再文, 张万轩. 三溴化金催化端炔与二芳基二硒醚反应合成炔基硒醚[J]. 应用化学, 34(10): 1134-1139
SHE Chuan, YU Pei, LUO Xingting, et al. Synthesis of Alkynyl Selenides by Gold Tribromide Catalyzed Reaction of Terminal Alkynes with Diaryl Diselenides[J]. Chinese Journal of Applied Chemistry, 34(10): 1134-1139  
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三溴化金催化端炔与二芳基二硒醚反应合成炔基硒醚
佘川, 余佩, 骆兴霆, 田再文, 张万轩*
湖北大学有机化工新材料湖北省协同创新中心,有机功能分子合成与应用教育部重点实验室 武汉 430062
通讯联系人:张万轩,教授; Tel:027-88662747; Fax:027-88663043; E-mail:zhangwx@hubu.edu.cn; 研究方向:有机合成
收稿日期:2016-12-19 修回日期:2017-02-13 接受日期:2017-03-29
基金:湖北大学有机功能分子合成与应用教育部重点实验室和大学生创新训练计划(201410512002)资助项目;
摘要

炔基硒醚是合成一些有机硒化合物的重要起始物。 本文研究发现,在三溴化金(AuBr3)催化下,端位炔和二芳基二硒醚在弱碱(如碳酸钾)存在下反应,生成炔基芳基硒醚,产率为69%~98%;在空气参与下,于80 ℃下进行反应,反应条件简单,且二硒醚的两个硒原子均可以被利用。 二甲基亚砜(DMSO)是合适的溶剂,在极性较小的溶剂(如甲苯、四氢呋喃)中,此反应不能进行。 芳基炔(如苯乙炔、对甲基苯乙炔、对氯苯乙炔等)、烯基炔(如环己烯乙炔)和烷基炔(如1-壬炔)均能顺利进行此反应。 当芳基炔苯环的间位或邻位连有取代基时,反应产率较低(69%~82%),而对位无论是连有吸电子基还是给电子基,该反应均可以得到很高的产率(95%)。

关键词: 三溴化金; 端炔; 二芳基二硒醚; 炔基硒醚
中图分类号:O627 文献标志码:A 文章编号:1000-0518(2017)10-1134-06
Synthesis of Alkynyl Selenides by Gold Tribromide Catalyzed Reaction of Terminal Alkynes with Diaryl Diselenides
SHE Chuan, YU Pei, LUO Xingting, TIAN Zaiwen, ZHANG Wanxuan
Key Laboratory for the Synthesis and Application of Organic Functional Molecules,Ministry of Education,Hubei Collaborative Innovation Center for Advanced Organic Chemical Material,Hubei University,Wuhan 430062,China
Corresponding author:ZHANG Wanxuan, professor; Tel:027-88662747; Fax:027-88663043; E-mail:zhangwx@hubu.edu.cn; Research interests:organic synthesis
Received:2016-12-19 Revised:2017-02-13 Accepted:2017-03-29
Fund:Supported by the Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, Hubei University and Stu-dent Innovation Training Program(No.201410512002)
Abstract

Alkynyl selenides are important starting materials for the synthesis of some organic selenides. In this paper, alkynyl selenides were synthesized by the reaction between terminal alkynes and diaryl diselenides catalyzed by gold tribromide(AuBr3) in the presence of a base such as potassium carbonate in good to excellent yields(69%~98%). The reaction was performed at 80 ℃ in air, and all the selenium atoms of diaryl diselenides could be taken into use. Dimethyl sulfoxide is a proper solvent. The reaction does not occur when less polar tetrahydrofuran or toluene is used as the solvent. Aryl, alkenyl and alkyl alkynes can smoothly react with diaryl diselenides under the above conditions. Para-substituted phenylacetylene(such as 4-ethynyltoluene, 1-ethynyl-4-methoxybenzene, 4-fluorophenylacetylene, 4-chlorophenylacetylene, etc.) gives rise to alkynyl selenides in good to excellent yields(78%~98%) whether the substituents are electron-donating or -withdrawing. Ortho- and meta-substituted phenylacetylene leads to relatively low yields(69%~82%). Non-aryl alkynes(such as 1-nonyne and 1-ethynylcyclohexene) also afford corresponding alkynyl selenides with high yields(95%).

Keyword: gold tribromide; terminal alkynes; diselenides; alkynyl selenides

有机硒化合物化学性质丰富多样,常常用作有机合成的中间体,而且一些含硒有机化合物具有重要的生理活性,因此有机硒化合物的合成是人们感兴趣的研究领域之一[1]。 炔基硒醚可以转化为多种有机硒化合物,是有机合成中重要的合成子[2,3,4]:它们可以通过氯羰基化反应、氢卤化反应、氢磺化反应、硼氢化反应转化为取代烯烃[5];此外,炔基硒化物可以作为环加成反应的亲双烯体[6]或用作 δ-氨基乙酰丙酸脱氢酶等氧化酶的抑制剂[7]。 因此,炔基硒醚是一类用途广泛的有机硒化合物。

利用炔基卤代物与二硒醚反应或者使用苯硒酰溴与RC≡CM(M=Li,Na,Mg)反应可以制得炔基硒醚类物质[8,9],但利用端位炔与二硒醚直接反应合成炔基硒醚,是更为原子经济的方法。 研究表明使用碘化亚铜[10,11]、三氯化铟[12]、纳米氧化铜[13]、纳米四氧化三铁[14]、氢氧化铯[15]作为催化剂,可以催化端位炔与二硒醚反应合成炔基硒醚。 我们研究发现利用三溴化金作为催化剂时,端位炔1很容易与二芳基二硒醚2反应得到炔基硒醚3,该反应在空气中可以顺利进行。 反应方程式如Scheme 1所示。

Scheme 1 The reaction of terminal alkynes with diaryl diselenides catalyzed by gold tribromide

1 实验部分
1.1 仪器和试剂

GCMS-QP2010型气质联用仪(日本岛津公司);Vario Micro Cube型元素分析仪(德国 Elementar公司);INOVA 600 MHz型核磁共振仪(美国瓦里安公司)或WIPM 400 MHz 型核磁共振仪(中国中科开物公司)。

三溴化金(99%)购于上海晶纯生化科技股份有限公司,二苯基二硒醚(97%)购于梯希爱(TCI)上海化成工业发展有限公司。 其它试剂或溶剂均为市售分析纯或化学纯试剂,购自上海阿拉丁试剂公司或武汉欣申试化工科技有限公司。

1.2 实验方法

先将端位炔(0.5 mmol)、三溴化金(0.05 mmol)加入反应管中,然后向反应管中依次加入二芳基二硒醚(0.25 mmol)、碳酸钾(0.5 mmol)和二甲基亚砜(2 mL),将反应混合物加热到80 ℃, 搅拌约8 h(用薄层色谱TCL监测反应)。 反应结束后加入水,用乙酸乙酯萃取,萃取所得有机层用无水硫酸钠干燥,过滤,旋蒸除去溶剂,剩余物用柱色谱分离(洗脱剂为石油醚)提纯。

1.3 产物表征

产物炔基硒醚3的测试数据如下。

苯基苯乙炔硒醚(3a)[14]:1H NMR(400 MHz,CDCl3), δ:7.61~7.56(m,2H),7.46~7.54(m,2H),7.36~7.22(m,6H);13C NMR(100 MHz,CDCl3), δ:131.87,129.69,128.9,128.18,127.23,123.27,103.09,69.32。

苯基-4-甲基苯乙炔硒醚(3b)[8]:1H NMR(400 MHz,CDCl3), δ:7.48(m,4H),7.34~7.28(m,3H),7.14(d, J=7.6 Hz,2H),2.33(m,3H);13C NMR(100 MHz,CDCl3), δ:137.36,131.82,130.51,130.47,129.62,129.56,128.60,128.6,125.04,123.40,102.45,68.88,21.18。

苯基-4-乙基苯乙炔硒醚(3c)[8]:1H NMR(400 MHz,CDCl3), δ:7.57(d, J=7.3 Hz,2H),7.42(d, J=8.2 Hz,2H),7.34~7.28(m,3H),7.27~7.23(m,1H),2.68~2.60(m,2H),1.25~1.19(m,3H) ;13C NMR (100 MHz,CDCl3), δ:145.28,132.00,129.63,129.24,128.97,128.04,127.10,120.44,103.22,68.23,28.97,15.46。

苯基-4-甲氧基苯乙炔硒醚(3d)[14]:1H NMR(400 MHz,CDCl3), δ:7.59~7.54(m,2H),7.47~7.42(m,2H),7.34~7.21(m,3H),6.87~6.81(m,2H),3.78(s,3H);13C NMR(100 MHz,CDCl3), δ:160.08,133.72,129.62,129.35,128.93,127.06,115.36,113.99,103.07,67.27,55.42。

苯基-4-氟苯乙炔硒醚(3e):1H NMR(400 MHz,CDCl3), δ:7.64~7.57(m,2H),7.49~7.43(m,1H),7.37~7.25(m,4H),7.14~7.05(m,2H);13C NMR(100 MHz,CDCl3), δ:162.62(d, J=248.7 Hz),133.76(d, J=7.4 Hz),129.54,129.04,128.72,127.13,119.24(d, J=3.0 Hz),115.60(d, J=22.0 Hz),101.68,69.01;MS(EI) m/z(%)=276(M+,48);C14H9FSe计算值/%:C 61.11,H 3.30;实测值/%:C 61.16,H 3.27。

苯基-4-氯苯乙炔硒醚(3f)[8]:1H NMR(400 MHz,CDCl3), δ:7.18~7.67(m,9H);13C NMR(100 MHz,CDCl3), δ:134.57;132.89;129.60;129.16;128.68;128.56,127.25;121.61;101.63;74.63。

苯基-2-氟苯乙炔硒醚(3g):1H NMR(400 MHz,CDCl3), δ:7.56(d, J=7.3 Hz,2H),7.49~7.42(m,2H),7.34~7.27(m,2H),7.25~7.21(m,1H),7.06~6.94(m,2H);13C NMR(100 MHz,CDCl3), δ:162.78(d, J=251.0 Hz),133.33,130.14(d, J=7.8 Hz),129.59,128.98,128.55,127.16,123.94(d, J=3.3 Hz),115.52(d, J=20.7 Hz),111.82(d, J=15.5 Hz),96.23,74.94(d, J=2.9 Hz);MS(EI) m/z(%)=276(M+,48);C14H9FSe计算值/%:C 61.11,H 3.30;实测值/%:C 61.08,H 3.31。

苯基-3-氯苯乙炔硒醚(3h):1H NMR(400 MHz,CDCl3), δ:7.57(d, J=7.3 Hz,2H),7.46(s,1H),7.40~7.23(m,6H);13C NMR(100 MHz,CDCl3), δ:134.16,131.40,129.68,129.62,129.55,129.21,128.72,128.41,127.31,124.79,101.34,71.27;MS(EI) m/z(%)=292(M+,47);C14H9ClSe计算值/%:C 57.66,H 3.11;实测值/%:C 57.62,H 3.14。

苯基壬炔硒醚(3i):1H NMR(400 MHz,CDCl3), δ:7.54~7.48(m,2H),7.32~7.22(m,3H),2.45 (t, J=7.08 Hz,2H),1.63~1.26(m,10H),0.89(t, J=7.0 Hz,3H);13C NMR(100 MHz,CDCl3), δ:129.35,129.31,128.53,126.65,104.74,57.34,31.71,28.81,28.76,28.68,22.59,20.53,14.03;MS(EI) m/z(%)=280(M+,46);C15H20Se计算值/%:C 64.51,H 7.22;实测值/%:C 64.43,H 7.16。

苯基环己烯乙炔硒醚(3j)[16]:1H NMR(400 MHz,CDCl3), δ:7.40(d, J=6.64 Hz,2H),6.19(s,3H),6.22~6.16(s,3H),2.55~2.40(m,4H),2.01~1.89(m,4H);13C NMR(100 MHz,CDCl3), δ:135.93,135.89,129.36,128.55,126.75,126.73,120.86,105.10,65.42,29.10,25.64,22.20,21.35。

4-甲基苯基苯乙炔硒醚(3k)[12]:1H NMR(400 MHz,CDCl3), δ:7.56~7.40(m,4H),7.38~7.27(m,3H),7.13(d, J=7.0 Hz,2H),2.32(s,3H);13C NMR(100 MHz,CDCl3), δ:137.19,130.34,130.29,129.45,129.40,128.29,124.87,123.23,102.28,69.70,21.01。

4-氯苯基苯乙炔硒醚(3l)[14]:1H NMR(400 MHz,CDCl3), δ:7.54~7.44(m,4H),7.35~7.26(m,5H);13C NMR(100 MHz,CDCl3), δ:133.21,131.75,130.30,129.63,128.74,128.36,127.07,122.86,103.32,68.59。

4-甲基苯基-4-甲基苯乙炔硒醚(3m)[17]:1H NMR(400 MHz,CDCl3), δ:7.46(d, J=8.0 Hz,2H),7.36(d, J=8.0 Hz,2H),7.11(d, J=6.3 Hz,4H),2.34(s,3H),2.32 (s,3H);13C NMR(100 MHz,CDCl3), δ:138.66,137.06,131.66,130.26,129.34,129.04,125.08,120.20,102.48,68.56,21.47,21.00。

4-氯苯基-4-甲基苯乙炔硒醚(3n)[17]:1H NMR(400 MHz,CDCl3), δ:7.48(d, J=8.56 Hz,2H),7.38(d, J=7.96 Hz,2H),7.27(d, J=8.56 Hz,2H),7.12(d, J=7.96 Hz,2H),2.34(s,3H);13C NMR(100 MHz,CDCl3), δ:139.05,133.13,131.75,130.17,129.57,129.11,127.29,119.81,103.53,67.56,21.49。

4-甲基苯基-4-甲氧基苯乙炔硒醚(3o):1H NMR(400 MHz,CDCl3), δ:7.50~7.40(m,4H),7.14(d, J=7.88 Hz,2H),6.86(d, J=8.84 Hz,2H),3.84~3.80(s,3H),2.34(s,3H);13C NMR(100 MHz,CDCl3), δ:159.85,137.01,133.48,130.27,129.21,125.22,115.35,113.90,102.26,67.60,53.30,21.00;MS(EI) m/z(%)=302(M+,37);C16H14OSe计算值/%:C 63.79,H 4.68;实测值/%:C 63.72,H 4.64。

4-氯苯基-4-甲氧基苯乙炔硒醚(3p):1H NMR(400 MHz,CDCl3), δ:7.56~7.40(m,4H),7.36(d, J=6.96 Hz,2H),6.86(d, J=8.72 Hz,2H),3.84~3.80(s,3H);13C NMR(100 MHz,CDCl3), δ:160.11,133.65,133.10,130.13,129.57,127.49,114.97,114.01,103.38,66.58,55.31;MS(EI) m/z(%)=322(M+,45);C16H11OSe计算值/%:C 56.01,H 3.45;实测值/%:C 56.08,H 3.48。

2 结果与讨论
2.1 反应条件的优化

首先以苯乙炔1a和二苯二硒醚2a为例,对反应条件进行了探讨。 发现在三溴化金催化下,以碳酸钾作为碱,二甲基亚砜(DMSO)为溶剂, 1a和2a在80 ℃时反应,可以得到目标产物炔基硒醚。 当物质量的比为 n(苯乙炔): n(二苯二硒醚):(碳酸钾)=1:0.5:1时,目标产物3a的产率达到92%。 在极性较小的溶剂(如THF或甲苯)中,反应不能进行;采用三乙胺或氢氧化钾作碱时,产率明显降低(产率分别为53%和35%);如果反应中不加碱,反应则不能进行。

2.2 多种端炔与二芳基二硒醚的反应

在优化的反应条件下,研究了一系列端位炔与不同的二芳基二硒醚的反应(表1)。 从表1可以看出,所尝试的底物均获得了良好到优秀的产率,达到69%~98%。 当苯炔的苯环上对位分别连有不同的吸电子基或供电子基时,对反应产率影响不大(表1,Entries 1~6),而相同取代基处在苯环不同的位置时,反应产率有明显的差别,如2-氟苯乙炔和3-氯苯乙炔与相应对位取代苯乙炔比,产率明显降低(表1,Entries 5和7;Entries 6和8),这可能是因为邻位或间位的取代基增大了位阻。 烷基炔和烯基炔也可以和二芳基二硒醚反应生成炔硒醚:分别以壬炔和环己烯乙炔为底物时,目标产物的收率均可以达到95%(表1,Entries 9和10)。 二苯基二硒醚的苯环上对位连有取代基(如—CH3或—Cl)时,产率稍低 (表1,Entries 11~16)。

表1 多种端炔与二芳基二硒醚的反应 a Table 1 Results for the reactions of terminal alkenes with diaryl diselenides a
2.3 反应机理的探讨

以上反应均是在敞口反应器中进行。 为了研究无空气参与时的反应情况,进行了以下对比实验:先向反应溶剂二甲基亚砜中鼓入N2气,持续约1 h后,加入1a(0.5 mmol)、2a(0.25 mmol)、碳酸钾(0.5 mmol)和三溴化金,在N2气保护下反应至苯乙炔消耗完,分离得到炔基硒醚3a(产率为65%)和 α, β-二苯硒基苯乙烯A(产率为35%)两种产物,化合物A应是PhSe-与3a进一步发生亲核加成反应而得到的(Scheme 2)[18,19]。

Scheme 2 The side reaction in the absence of air

以上实验说明反应体系中缺乏空气时,PhSe-不能被有效氧化,导致副反应发生而产生化合物A, 同时也导致3a的产率下降。 因此,推测该反应机理如Scheme 3所示[15]:在反应开始时,三溴化金与端炔配位形成中间体4,然后在碳酸钾作用下脱去质子形成中间体5, 中间体5中的炔负离子亲核进攻二硒醚中硒原子形成炔硒醚3和中间体6。 空气中的氧将6中的芳基硒负离子氧化生成原料二硒醚2,再参与下一轮反应循环,这样使二硒醚中的两个硒原子均可能与炔反应生成炔基硒醚;同时,6中芳基硒负离子被氧化后脱离金离子,使三溴化金再生,实现催化循环。

Scheme 3 Proposed mechanism for the reaction

3 结 论

本文发展了一种高效合成炔硒醚的新方法。 在三溴化金催化下,以碳酸钾为碱,二甲基亚砜为溶剂,温度为80 ℃时顺利地实现了端位炔与二芳基二硒醚的反应,生成炔基硒化物。 反应底物适用性广、产率高,反应可以在空气存在下进行,操作方便。

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