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CN108250115B - 从叔胺偶联合成芳基硫醚的方法 - Google Patents

从叔胺偶联合成芳基硫醚的方法 Download PDF

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CN108250115B
CN108250115B CN201810173730.XA CN201810173730A CN108250115B CN 108250115 B CN108250115 B CN 108250115B CN 201810173730 A CN201810173730 A CN 201810173730A CN 108250115 B CN108250115 B CN 108250115B
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thiophenol
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CN108250115A (zh
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曾庆乐
江文龙
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Chengdu Univeristy of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/26—Separation; Purification; Stabilisation; Use of additives
    • C07C319/28—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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
    • C07D233/84—Sulfur atoms
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    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles 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 in position 2
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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    • C07—ORGANIC CHEMISTRY
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    • 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
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Abstract

芳基硫醚在医药、农业、染料工业和功能材料领域有着广泛的用途，对人类的生产生活有着深远的影响。本发明首次以芳基叔胺一步合成芳基硫醚类化合物的方法,即在铜盐催化N,N‑二甲基‑1‑芳基乙胺与(杂)芳基硫酚进行C‑S偶联合成芳基硫醚。本发明提供的方法具有产率高，原料易得，条件简单，环保等优点。

Description

从叔胺偶联合成芳基硫醚的方法
技术领域
该专利涉及有机合成、药物合成、有机化工的研究领域，具体的讲，就是从N,N-二甲基-1-芳基乙胺和巯基化合物一步催化合成芳基硫醚，特别是手性的硫醚。
背景技术
芳基硫醚广泛存在于药物和生物活性的化合物中(J. Med. Chem., 2000, 43：4025-4040; J. Med. Chem., 2001, 44：202-1210; J. Med. Chem., 2007, 50: 3046-3053)。手性芳基硫醚还可以作为手性配体和有机催化剂用于不对称催化反应(Eur. J.Org. Chem., 2002: 2776; J. Mol. Catalysis A: Chem., 2009, 307(1): 149-153; J.Am. Chem. Soc., 2018, 140 (7), 2693–2699)。此外，芳基硫醚还可以作为有机合成的中间体(J. Med. Chem., 1996, 39:3556-3563; J. Med. Chem., 2006, 49：947-954;US5149357, 1992)。
经典的芳基硫醚的合成方法(Bull. Chem. Soc. Jpn., 1980, 50(5): 1385-1389; J. Org, Chem. 2001, 66(5):8677-8681；Adv. Synth. Catal., 2009, 351(16):2558-2562)，经典合成的主要方法：硫酚或硫醇在碱性条件下与卤代烃反应能够生成对称或不对称硫醚、砜类或亚砜类化合物被还原生成对称或不对称硫醚、利用不同金属及配体来催化偶联合成硫醚。该系列的方法适合对称或不对称硫醚合成，但是合成中操作条件复杂、复杂昂贵的配体、部分反应底物活性不高、成本高、污染环境。最近文献报道了通过利用苯炔前体活化N,N-二甲基-1-芳基乙胺(Org. Lett. 2017, 19, 1554-1557)来合成硫醚，但是只能利用苯炔前体来活化，其他试剂未能活化进行反应，而且苯炔前体的合成操作繁琐、成本高，危险性大。还有一些合成芳基硫醚的方法，而且原料结构比较复杂(Tetrahedron Lett. 2007, 48, 8125.)，或者其它一些缺点。
铜催化C-S偶联被科研人员发现以后一直在研究，但是未见与本申请类似的文献报道。
发明内容
本发明提供一种芳基硫醚的合成方法。
本发明公开的芳基硫醚的合成方法由一步完成，即在碱存在下，铜催化N,N-二甲基-1-芳基乙胺和芳基硫酚发生C-S偶联反应一步合成芳香硫醚。
结合下面的实施例更详细地阐述本发明，并不认为它们是对本发明范围的限制。
具体实施方式
实施例一
往烘干带磁力搅拌子的磨口试管里加入N,N-二甲基-1-苯基乙胺(1.0摩尔)、三氟甲磺酸甲酯(1.1毫摩尔)、二氧六环(2.0毫升)反应5分钟，然后依次加入对甲基硫酚(2.0摩尔)、碳酸钾(2.0毫摩尔)、六氟磷酸四乙腈铜(0.1毫摩尔)、二氧六环(3毫升)，最后用橡皮塞密封磨口试管。把该试管放到110oC油浴锅中加热搅拌反应20小时。然后让反应混合液冷却到室温，用饱和食盐水淬灭反应，用10毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥。滤液浓缩所得的粗产物用硅胶柱层析、以石油醚洗脱得到无色油状液体(1-苯乙基)(4-甲苯基)硫醚，产率94%。1H NMR (400 MHz, CDCl3) δ = 7.28– 7.22 (m, 4H), 7.22– 7.15 (m, 3H), 7.01 (d, J = 7.9 Hz, 2H), 4.25 (q, J = 7.0 Hz, 1H), 2.28 (s,3H), 1.59 (d, J = 7.0 Hz, 3H).13C NMR (100 MHz, CDCl3) δ = 143.39 (s), 137.39(s), 133.22 (s), 131.30 (s), 129.48 (s), 128.36 (s), 127.32 (s), 127.07 (s),77.37 (s), 77.05 (s), 76.73 (s), 48.40 (s), 22.20 (s), 21.13 (s).
实施例二
往烘干带磁力搅拌子的磨口试管里加入(S)-N,N-二甲基-1-苯基乙胺(1.0摩尔)、三氟甲磺酸甲酯(1.1毫摩尔)、二氧六环(2.0毫升)反应5分钟，然后把对甲基硫酚(2.0摩尔)、碳酸钾(2.0毫摩尔)、六氟磷酸四乙腈铜(0.1毫摩尔)、二氧六环(3毫升)用橡皮塞密封的试管。把该试管放到110oC油浴锅中加热搅拌反应20小时。然后让反应混合液冷却到室温，用饱和食盐水淬灭反应，用10毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸钠干燥。滤液浓缩所得的粗产物用硅胶柱层析、以石油醚洗脱得到无色油状液体(R)-(1-苯乙基)(4-甲苯基)硫醚，产率92%。该(R)-(1-苯乙基)(4-甲苯基)硫醚在液相色谱仪上用手性液相色谱柱日本大赛璐公司生产的Chiralcel OJ-H高效柱(4.6毫米直径、250毫米长、5微米粒径)(流动相：正己烷/异丙醇体积比99.5/0.5)进行对映体过量分析，在室温下检测的出峰时间为9.3分钟(S构型)和13.8分钟(R构型)，分析结果表明，该产物的对映体过量值为97%ee(R构型)。
[α]D 20 =-168.0o(c= 1.7, EtOAc); 1H NMR (400 MHz, CDCl3)δ= 7.28-7.22 (m,4H), 7.22-7.15 (m, 3H), 7.01 (d, J = 7.9 Hz, 2H), 4.25 (q, J = 7.0 Hz, 1H),2.28 (s, 3H), 1.59 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ = 143.39(s), 137.39 (s), 133.22 (s), 131.30 (s), 129.48 (s), 128.36 (s), 127.32 (s),127.07 (s), 77.37 (s), 77.05 (s), 76.73 (s), 48.40 (s), 22.20 (s), 21.13 (s).
实施例三
碘化亚铜代替实施例一中的六氟磷酸四乙腈铜，得到无色油状液体(1-苯乙基)(4-甲苯基)硫醚的产率为85%。
实施例四
碳酸铯代替实施例一中的碳酸钾，得到无色油状液体(1-苯乙基)(4-甲苯基)硫醚的产率为87%。
实施例五
磷酸钾代替实施例一中的碳酸钾，得到无色油状液体(1-苯乙基)(4-甲苯基)硫醚的产率为85%。
实施例六
邻甲基硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(1-苯乙基)(2-甲苯基)硫醚的产率为85%。
实施例七
(S)-N,N-二甲基-1-苯基乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，邻甲基硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(R)-(1-苯乙基)(2-甲苯基)硫醚的产率为84%。该(R)-(1-苯乙基)(2-甲苯基)硫醚在液相色谱仪上用手性液相色谱柱日本大赛璐公司生产的Chiralcel OJ-H高效柱(4.6毫米直径、250毫米长、5微米粒径)(流动相：正己烷/异丙醇体积比97/3)进行对映体过量分析，在室温下检测的出峰时间为10.5分钟(S构型)和14.5分钟(R构型)，分析结果表明，该产物的对映体过量值为97%ee(R构型)。
实施例八
对溴苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(4-溴苯基) (1-苯乙基)硫醚的产率为83%。
实施例九
(S)-N,N-二甲基-1-苯基乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，对溴苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(R)-(4-溴苯基) (1-苯乙基)硫醚的产率为81%。该(S)-(4-溴苯基) (1-苯乙基)硫醚在液相色谱仪上用手性液相色谱柱日本大赛璐公司生产的Chiralcel OJ-H高效柱(4.6毫米直径、250毫米长、5微米粒径)(流动相：正己烷/异丙醇体积比99.5/0.5)进行对映体过量分析，在室温下检测的出峰时间为7.9分钟(S构型)和15.1分钟(R构型)，分析结果表明，该产物的对映体过量值为97%ee(R构型)。
实施例十
2-巯基苯并噁唑代替实施例一中的对甲基苯硫酚，得到无色油状液体2-((1-苯乙基)巯基)苯并噁唑的产率为75%。
实施例十一
(S)-N,N-二甲基-1-苯基乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，2-巯基苯并噁唑代替实施例一中的对甲基苯硫酚，得到无色油状液体(R)-2-((1-苯乙基)巯基)苯并噁唑的产率为78%。该(R)-2-((1-苯乙基)巯基)苯并噁唑在液相色谱仪上用手性液相色谱柱日本大赛璐公司生产的Chiralcel OJ-H高效柱(4.6毫米直径、250毫米长、5微米粒径)(流动相：正己烷/异丙醇体积比95/5)进行对映体过量分析，在室温下检测的出峰时间为4.9分钟(S构型)和7.9分钟(R构型)，分析结果表明，该产物的对映体过量值为97%ee(R构型)。
实施例十二
对氟苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(4-氟苯基)(1-苯乙基)硫醚的产率为85%。1H NMR (400 MHz, CDCl3) δ = 7.22 – 7.10 (m, 7H), 6.86 –6.78 (m, 2H), 4.15 (q, J = 7.0 Hz, 1H), 1.53 (d, J = 7.0 Hz, 3H). 13C NMR (100MHz, CDCl3) δ = 163.78 (s), 161.32 (s), 143.03 (s), 135.72 (d, J = 8.2 Hz),129.77 (d, J = 3.3 Hz), 128.37 (s), 127.25 (d, J = 11.7 Hz), 115.83 (s),115.62 (s), 77.36 (s), 77.04 (s), 76.73 (s), 48.91 (s), 29.77 (s),21.93 (s).
实施例十三
3,4-二甲基苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(3,4-二甲基苯基)(1-苯乙基)硫醚的产率为87%。1H NMR (400 MHz, CDCl3) δ = 7.24 – 7.10 (m,5H), 7.02 – 6.89 (m, 3H), 4.20 (q, J = 7.0 Hz, 1H), 2.12 (d, J = 11.5 Hz,6H), 1.53 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ = 143.44 (s), 137.02(s), 136.04 (s), 134.33 (s), 131.52 (s), 130.55 (s), 129.96 (s), 128.33 (s),127.34 (s), 127.04 (s), 77.35 (s), 77.03 (s), 76.72 (s), 48.29 (s), 29.72(s), 22.23 (s), 19.52 (d, J = 19.1 Hz).
实施例十四
4-氯苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(4-氯苯基)(1-苯乙基)硫醚的产率为80%。1H NMR (400 MHz, CDCl3) δ = 7.22 – 7.16 (m, 4H), 7.13(ddd, J = 7.2, 4.8, 2.4 Hz, 1H), 7.10 (d, J = 5.4 Hz, 4H), 4.21 (q, J = 7.0Hz, 1H), 1.54 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ =142.90 (s),133.97 (s), 133.45 (d, J = 15.3 Hz), 128.83 (s), 128.47 (s), 128.24 (s),127.29 (d, J = 2.0 Hz), 77.37 (s), 77.06 (s), 76.74 (s), 48.29 (s), 29.74(s), 22.21 (s).
实施例十五
3-甲基苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(1-苯乙基)(3-甲苯基)硫醚的产率为81%。1H NMR (400 MHz, CDCl3) δ = 7.39 – 7.29 (m, 4H),7.29 – 7.24 (m, 1H), 7.20 – 7.12 (m, 3H), 7.10 – 7.01 (m, 1H), 4.39 (q, J =7.0 Hz, 1H), 2.32 (s, 3H), 1.69 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3)δ = 143.33 (s), 138.43 (s), 134.91 (s), 133.15 (s), 129.43 (s), 129.05 –128.40 (m), 128.08 (d, J = 20.0 Hz), 127.45 (d, J = 19.4 Hz), 127.15 (s),77.42 (s), 77.10 (s), 76.78 (s), 47.94 (s), 29.77 (s), 22.38 (s), 21.29 (s).
实施例十六
2,4-二氯苯硫酚代替实施例一中的对甲基苯硫酚，得到无色油状液体(2,4-二氯苯基)(1-苯乙基)硫醚的产率为70%。1H NMR (400 MHz, CDCl3) δ = 7.29 (d, J = 2.2Hz, 1H), 7.26 – 7.16 (m, 4H), 7.15 – 7.10 (m, 1H), 7.04 (t, J = 6.7 Hz, 1H),6.95 (dd, J = 8.4, 2.2 Hz, 1H), 4.37 (q, J = 7.0 Hz, 1H), 1.56 (d, J = 7.0Hz, 3H). 13C NMR (100 MHz, CDCl3) δ = 142.36 (s), 136.85 (s), 133.76 (s),133.22 (d, J = 4.5 Hz), 129.54 (s), 128.59 (s), 127.48 (s), 127.20 (d, J =4.2 Hz), 77.39 (s), 77.07 (s), 76.75 (s), 46.73 (s), 29.74 (s), 22.25 (s).
实施例十七
3-氟苯硫酚代替实施例一中的对甲基苯硫酚,得到无色油状液体(3-氟苯基)(1-苯乙基)硫醚的产率为84%。1H NMR (400 MHz, CDCl3) δ = 7.26 – 7.16 (m, 4H), 7.16 –7.02 (m, 2H), 6.97 – 6.92 (m, 1H), 6.91 – 6.86 (m, 1H), 6.77 (tdd, J = 8.5,2.5, 0.9 Hz, 1H), 4.28 (q, J = 7.0 Hz, 1H), 1.55 (d, J = 7.0 Hz, 3H). 13C NMR(100 MHz, CDCl3) δ 163.79 (s), 161.32 (s), 142.80 (s), 137.74 (d, J = 7.8Hz), 129.93 (d, J = 8.5 Hz), 128.57 (s), 128.33 (s), 127.50 (d, J = 19.8 Hz),127.37 – 126.86 (m), 118.46 (s), 118.24 (s), 113.98 (s), 113.77 (s), 77.42(s), 77.11 (s), 76.79 (s), 47.75 (s), 29.78 (s), 22.47 (s).
实施例十八
2-巯基-1,3,4-噻二唑代替实施例一中的对甲基苯硫酚, 2-((1-苯乙基)巯基)-1,3,4-噻二唑的产率为78%。1H NMR (400 MHz, CDCl3) δ = 8.91 (d, J = 10.6 Hz, 1H),7.37 – 7.32 (m, 2H), 7.28 – 7.22 (m, 2H), 7.22 – 7.17 (m, 1H), 5.01 (q, J =7.0 Hz, 1H), 1.75 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 152.01 (s),141.29 (s), 128.81 (s), 128.69 (d, J = 20.6 Hz), 128.05 (s), 127.44 (s),77.43 (s), 77.11 (s), 76.79 (s), 48.49 (s), 29.72 (s), 22.38 (s).
实施例十九
甲巯咪唑代替实施例一中的对甲基苯硫酚,1-甲基-2-((1-苯乙基)巯基)-1H-咪唑的产率为77%。1H NMR (400 MHz, CDCl3) δ = 7.21 – 7.13 (m, 3H), 7.08 – 7.02 (m,3H), 6.76 (d, J = 1.1 Hz, 1H), 4.42 (q, J = 7.1 Hz, 1H), 3.08 (s, 3H), 1.63(d, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ = 142.84 (s), 139.85 (s),129.84 (s), 128.42 (s), 127.45 (s), 126.92 (s), 122.58 (s), 77.40 (s), 77.09(s), 76.77 (s), 49.27 (s), 33.12 (s), 32.76 (s), 29.39 (s), 22.72 (s).
实施例二十
1-甲基-5-巯基-1H-四氮唑代替实施例一中的对甲基苯硫酚,1-甲基-5-((1-苯乙基)巯基)-1H-四唑的产率为83%。1H NMR (400 MHz, CDCl3) δ = 7.30 – 7.12 (m, 5H),4.89 (q, J = 7.0 Hz, 1H), 3.61 (s, 3H), 1.76 (d, J = 7.0 Hz, 3H). 13C NMR (100MHz, CDCl3) δ 152.92 (s), 140.99 (s), 128.94 – 128.17 (m), 127.18 (d, J =22.1 Hz), 126.75 (s), 77.49 (s), 77.17 (s), 76.85 (s), 60.40 (s), 48.43 (s),33.40 (s), 21.90 (s).
实施例二十一
2-巯基-5-甲基-1,3,4-噻二唑代替实施例一中的对甲基苯硫酚，2-甲基-5-((1-苯乙基)巯基)-1,3,4-噻二唑的产率为77%。1H NMR (400 MHz, CDCl3) δ = 7.33 (dd, J =5.3, 3.4 Hz, 2H), 7.27 – 7.21 (m, 2H), 7.20 – 7.15 (m, 1H), 4.91 (q, J = 7.0Hz, 1H), 2.59 (s, 3H), 1.71 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ =165.67 (s), 164.38 (s), 141.52 (s), 128.73 (s), 128.49 (s), 128.02 (d, J =17.2 Hz), 127.43 (s), 77.47 (s), 77.15 (s), 76.83 (s), 48.30 (s), 29.73 (s),22.38 (s), 15.68 (s).
实施例二十二
N,N-二甲基-1-(2-溴苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(2-溴苯基)乙基)(4-甲苯基)硫醚的产率为80%。1H NMR (400 MHz,CDCl3) δ = 7.55 (s, 1H), 7.23 (s, 3H), 7.17 – 6.97 (m, 4H), 4.93 (s, 1H),2.32 (s, 3H), 1.70 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 143.50 (d), 137.59(s), 133.79 (s), 132.96 (s), 132.22 (s), 130.73 (s), 129.44 (s), 128.29 (s),127.57 (d, J = 19.2 Hz), 121.75 (s), 42.52 (s), 21.96 (s), 21.15 (s).
实施例二十三
N,N-二甲基-1-(4-甲基苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体4-甲苯基(1-(4-甲苯基)乙基)硫醚的产率为88%。1H NMR (400 MHz,CDCl3) δ = 7.18 (s, 1H), 7.11 (t, J = 8.2 Hz, 4H), 6.98 (dd, J = 17.1, 7.9Hz, 4H), 4.16 (p, J = 7.0 Hz, 1H), 2.24 (dd, J = 13.3, 5.5 Hz, 6H), 1.50 (dd,J = 7.0, 2.5 Hz, 3H).
实施例二十四
N,N-二甲基-1-(2-氟苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(2-氟苯基)乙基)(4-甲苯基)硫醚的产率为82%。1H NMR (400 MHz,CDCl3) δ = 7.29 (tt, J = 4.8, 2.4 Hz, 1H), 7.15 – 7.06 (m, 3H), 7.05 – 6.94(m, 3H), 6.92 – 6.86 (m, 1H), 4.57 (q, J = 7.1 Hz, 1H), 2.23 (s, 3H), 1.53(d, J = 7.1 Hz, 3H).
实施例二十五
N,N-二甲基-1-萘乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(1-萘基)乙基)(4-甲苯基)硫醚的产率为90%。1H NMR (400 MHz, CDCl3) δ = 8.24(d, J = 8.5 Hz, 1H), 7.90 – 7.85 (m, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.59 –7.46 (m, 3H), 7.40 (dd, J = 14.9, 7.4 Hz, 1H), 7.24 – 7.20 (m, 2H), 7.04 (d,J = 7.9 Hz, 2H), 5.09 (q, J = 6.9 Hz, 1H), 2.30 (s, 3H), 1.76 (d, J = 6.9 Hz,3H).
实施例二十六
N,N-二甲基-1氢-茚1-胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(2,3-二氢-1H-茚-1-基)乙基)(4-甲苯基)硫醚的产率为88%。1H NMR (400 MHz,CDCl3) δ = 7.33 – 7.25 (m, 3H), 7.23 – 7.13 (m, 3H), 7.10 (d, J = 7.9 Hz,2H), 4.69 (dd, J = 7.4, 4.0 Hz, 1H), 3.00 (dt, J = 15.7, 7.8 Hz, 1H), 2.83(ddd, J = 15.8, 8.4, 4.4 Hz, 1H), 2.58 – 2.43 (m, 1H), 2.33 (d, J = 6.2 Hz,3H), 2.25 – 2.14 (m, 1H), 1.55 (s, 1H).
实施例二十七
N,N-二甲基-1-(4-溴苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(4-溴苯基)乙基)(4-甲苯基)硫醚的产率为84%。1H NMR (400 MHz,CDCl3) δ = 7.41 – 7.35 (m, 2H), 7.18 – 7.09 (m, 4H), 7.03 (d, J = 7.9 Hz,2H), 4.27 – 4.13 (m, 1H), 2.30 (s, 3H), 1.58 (d, J = 7.0 Hz, 3H).
实施例二十八
N,N-二甲基-1-(4-氟苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(4-氟苯基)乙基)(4-甲苯基)硫醚的产率为76%。1H NMR(400 MHz, CDCl3)δ = 7.23 (d, J = 5.0 Hz, 4H), 7.18 (dd, J = 55.0, 20.0 Hz, 8H), 4.33 (s, 1H),2.32 (s, 3H), 1.72 (s, 3H).
实施例二十九
N,N-二甲基-1-(4-甲氧基苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(4-甲氧基苯基)乙基)(4-甲苯基)硫醚的产率为83%。1H NMR (400MHz, CDCl3) δ =7.23 (d, J = 5.0 Hz, 4H), 7.16 (s, 2H), 7.09 (s, 2H), 4.33 (s,1H), 2.32 (s, 3H), 1.72 (s, 3H).
实施例三十
N,N-二甲基-1-(3-硝基苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(1-(4-硝基苯基)乙基)(4-对甲苯基)硫醚的产率为87%。1H NMR (400MHz, CDCl3) δ = 8.04 (ddd, J = 4.8, 3.8, 2.2 Hz, 2H), 7.60 – 7.53 (m, 1H),7.41 (ddd, J = 12.2, 8.7, 4.6 Hz, 1H), 7.18 – 7.10 (m, 2H), 7.03 (d, J = 7.9Hz, 2H), 4.32 (q, J = 7.0 Hz, 1H), 2.29 (s, 3H), 1.65 (d, J = 7.1 Hz, 3H).
实施例三十一
N,N-二甲基-1-(4-三氟甲基苯基)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体(4-甲苯基)(1-(4-三氟甲基苯基)乙基)硫醚的产率为85%。1H NMR(400 MHz, CDCl3) δ = 7.51 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 7.19– 7.13 (m, 2H), 7.03 (d, J = 7.9 Hz, 2H), 4.28 (q, J = 7.0 Hz, 1H), 2.31 (d,J = 6.7 Hz, 3H), 1.62 (d, J = 7.0 Hz, 3H).
实施例三十二
N,N-二甲基-1-(2-噻吩)乙胺代替实施例一中的N,N-二甲基-1-苯基乙胺，得到无色油状液体2-(1-(4-对甲苯巯基)乙基)噻吩的产率为83%。1H NMR (400 MHz, CDCl3) δ =7.24 (dt, J = 3.8, 2.4 Hz, 2H), 7.17 (dd, J = 5.1, 1.2 Hz, 1H), 7.07 (d, J =7.9 Hz, 2H), 6.86 (dd, J = 5.1, 3.5 Hz, 1H), 6.80 – 6.76 (m, 1H), 4.54 (q, J= 6.8 Hz, 1H), 2.32 (s, 3H), 1.68 (d, J = 7.0 Hz, 3H).
实施例三十三
N,N-二甲基-L-苯丙氨酸甲酯代替实施例一中的N,N-二甲基-1-苯基乙胺，得到白色固体(R)-2-苯基-2-(4-对甲苯巯基)乙酸甲酯的产率为90%。1H NMR (400 MHz, CDCl3) δ7.40 – 7.31 (m, 2H), 7.28 – 7.20 (m, 4H), 7.19 (s, 1H), 7.00 (d, J = 7.9 Hz,2H), 4.77 (s, 1H), 3.65 – 3.53 (m, 3H), 2.24 (s, 3H)。

Claims (2)

1.一种芳基硫醚的合成方法，其特征在于：在三氟甲磺酸甲酯和碱存在下，铜催化N,N-二甲基-1-芳基乙胺和硫酚在二氧六环中进行C-S偶联一步合成芳基硫醚；所说的N,N-二甲基-1-芳基乙胺为N,N-二甲基-1-苯基乙胺、N,N-二甲基-1-(4-甲基苯基)乙胺、N,N-二甲基-1-(2-溴苯基)乙胺、N,N-二甲基-1-(4-溴苯基)乙胺、N,N-二甲基-1-(2-氟苯基)乙胺、N,N-二甲基-1-(4-氟苯基)乙胺、N,N-二甲基-1-(4-三氟甲基苯基)乙胺、N,N-二甲基-1-(3-硝基苯基)乙胺、N,N-二甲基-1-(4-甲氧基苯基)乙胺、N,N-二甲基-1-萘乙胺；有手性点的N,N-二甲基-1-芳基乙胺的构型为R构型、S构型和消旋体；产物的构型由N,N-二甲基-1-芳基乙胺的构型决定，反应过程中原料的构型发生翻转；所说的硫酚为4-甲基苯硫酚、4-氟苯硫酚、3,4-二甲基苯硫酚、4-溴苯硫酚、4-氯苯硫酚、3-甲基苯硫酚、2,4-二氯苯硫酚、2-甲基苯硫酚、3-氟苯硫酚，2-巯基苯并噁唑、2-巯基-1,3,4-噻二唑、2-巯基-5-甲基-1,3,4-噻二唑、2-巯基-4,6-二甲基嘧啶、甲巯咪唑、1-甲基-5-巯基-1H-四氮唑；所说的铜催化剂为六氟磷酸四乙腈铜和碘化亚铜。
2.权利要求书1所述的一种芳基硫醚的合成方法，其特征在于所说的碱为碳酸钾、碳酸铯或者磷酸钾。
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