CN111233600B - 一种芳基(硫属杂芳基)甲基砜的合成方法 - Google Patents

一种芳基(硫属杂芳基)甲基砜的合成方法 Download PDF

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CN111233600B
CN111233600B CN202010089739.XA CN202010089739A CN111233600B CN 111233600 B CN111233600 B CN 111233600B CN 202010089739 A CN202010089739 A CN 202010089739A CN 111233600 B CN111233600 B CN 111233600B
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曾庆乐
库楚酷拉·拉纳卡·雷德
郑文婷
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Abstract

砜是重要的药物和生物活性化合物。砜被广泛用作药物，例如用于预防阿尔茨海默氏病的药物γ‑分泌酶抑制剂，并且广泛的应用于生物活性化合物，天然产物和农业化学品中，例如现在流行的除草剂甲基磺草酮。砜也最常被用作有机合成的中间体。另一方面，硫属元素杂环支架具有生物活性，例如抗肿瘤药和抗增殖药。众所周知，噻吩，呋喃和硒化合物具有多种生物活性，例如抗炎药，抗HIV PR抑制剂，NQO2抑制剂和抗癌剂。本专利开发了一种简便高效的布朗斯特酸，即硫酸，催化的三组分在水中反应合成芳基(硫属杂芳基)甲基砜，产率良好至很高，底物范围宽。我们的合成方法是环保，经济，无需金属催化。该砜产物可以有效地转化成杀菌剂类似物和芳基杂芳基酮。

Description

一种芳基(硫属杂芳基)甲基砜的合成方法
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，具体的方法就是亚磺酸钠、芳基 /烷基醛和硫属杂环化合物进行三组分反应一步合成芳基(硫属杂芳基)甲基砜类化合物。
背景技术
砜被广泛用作药物，例如用于预防阿尔茨海默氏病的药物γ-分泌酶抑制剂(I.Churcher,D. Beher,J.D.Best,J.L.Castro,E.E.Clarke,A.Gentry,T.Harrison,L.Hitzel,E.Kay,S.Kerrad,H. D.Lewis,P.M.Gutierrez,R.M.Smith,P.J.Oakley,M.Reilly,D.E.Shaw,M.S.Shearman,M.R. Teall,S.Williams and J.D.J.Wrigley,Bioorg.Med.Chem.Lett.,2006,16,280.)，也应用于生物活性化合物((a)G.Andrei,L.Naesens,R.Snoeck and C.E.Stephens,Patent:WO 2012/113920；(b)J. M.Caron,Patent:WO 2010/141956；(c)P.K.Chakravarty,P.P.Shao,Patent:WO 2010/036596；(d)Y.Harrak,G.Casula,J.Basset,G.Rosell,S.Plescia,D.Raffa,M.G.Cusimano,R.Pouplanaand M. D.Pujol,J.Med.Chem.,2010,53,6560；(e)T.K.Sasikumar,L.Qiang,D.A.Burnett,D.Cole,R. Xu,H.Li,W.J.Greenlee,J.Clader,L.Zhang and L.Hyde,Bioorg.Med.Chem.Lett.,2010,20, 3632；(f)L.Legros,J.R.Dehli and C.Bolm,Adv.Synth.Catal.,2005,347,19.)，天然产物((a)M. R.Prinsep,J.W.Blunt,M.H.G.Munro,J.Nat.Prod.,1991,54,1068.(b)S.S.P.Chou and C.J.J. Wu,Tetrahedron,2012,68,5025.(c)L.Chen,Z.Hua,G.Li,and Z.Jin,Org.Lett.,2011,13,3580.)，和农业化学品，例如现在流行的除草剂甲基磺草酮((a)D.Cornes,Patent:WO 2002/100173.(b)R.A.Wichert and T.H.Beckett,WO 2002/019823.)。砜也最常被用作有机合成的中间体。它们也被广泛用作有机合成中的重要中间体(N.S.Simpkins,Sulfones in OrganicSynthesis； Pergamon Press:Oxford,1993.)。
另一方面，硫属杂环支架具有生物活性，例如抗肿瘤药(V.Alcolea,D.Plano,I.Encío,J.A. Palop,A.K.Sharma,C.Sanmartín.,Eur.J.Med.Chem.2016,123,407)和抗增殖药(P.Begines,A. Oliete,O.Lopez,I.Maya,G.B.Plata,J.M.Padron andJ.G.F.Bolanos FutureMed.Chem.2018, 10,319.)。众所周知，噻吩，呋喃和硒化合物具有多种生物活性，例如抗炎药(P.R.Kumar,S. Raju,P.S.Goud,M.Sailaja,M.R.Sarma,G.O.Reddy,M.P.Kumar,V.V.R.M.K.Reddy,T. Suresha,P.Hegdeb,Bioorg.Med.Chem.2004,12,1221.)，抗HIV PR抑制剂(Bonini,C.；Chiummiento,L.；Bonis,M.D.；Funicello,M.；Lupattelli,P.；Suanno,G.；Berti,F.；Campaner,P. Tetrahedron 2005,61,6580.)，NQO2(Soraya Alnabulsi,Buthaina Hussein,Elham Santina,Izzeddin Alsalahat,Manikandan Kadirvel,Rachael N.Magwaza,Richard A.Bryce,Carl H.Schwalbe,Alex G.Baldwin,Ilaria Russo,Ian J.Stratford,Sally Freeman,Bioorg.Med.Chem.Lett.2018,28,1292.)抑制剂和抗癌剂((a)A.P.Fernandes,V.Gandin,Biochim.Biophys.Acta 2015,1850,1642.(b)M. Wallenberg,S.Misra,M.Bjornstedt,BasicClin.Pharmacol.Toxicol.2014,114,377.)。最近，在药物化学项目中着手研究α-支化杂环苄基砜的结构-活性关系(SAR)(T.Knauber and J.Tucker,J. Org.Chem.2016,81,5636.)。基于此重要性，我们拟开发芳基(硫属杂芳基)甲基砜的新合成方法。
我们在此提供一种在水中进行布朗斯特酸催化的无金属三组分反应，得到具有广泛底物范围的芳基(硫属杂芳基)甲基砜，并通过新的合成方法将产物转化为其他有价值的分子。
尽我们所知，未见与本申请相同的文献报道。
发明内容
本发明提供一种芳基(硫属杂芳基)甲基砜的合成方法。
本发明公开的芳基(硫属杂芳基)甲基砜的合成方法均一步完成，即在水中，布朗斯特酸 (优选的布朗斯特酸催化剂是硫酸)催化芳基/烷基醛，烃基亚磺酸钠和硫属杂环化合物发生三组分反应，一步合成芳基(硫属杂芳基)甲基砜，反应通式如下。其中，芳基/烷基醛为烷基醛、芳基醛和杂芳基醛。硫属杂环化合物为噻吩、呋喃和硒吩。烃基亚磺酸钠为芳基亚磺酸钠和烷基亚磺酸钠。
Figure DEST_PATH_IMAGE001
结合下面的实施例，更详细地阐述本发明，但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
向装有搅拌子的25mL玻璃试管中加入苯甲醛(1.5mmol)，2-甲基噻吩(1mmol)，硫酸 (0.5当量)和2mL水。在60℃下预热的油浴中将试管搅拌15分钟，然后缓慢加入苯亚磺酸钠(1mmol)。将反应混合物在60℃下搅拌。7小时后，通过TLC检查反应进程并确认反应完成。将反应混合物冷却至室温。然后将水(10mL)加入到反应混合物中，将其用乙酸乙酯(10mL)萃取三次。合并的有机层经无水MgSO4干燥，过滤，并在减压下浓缩。残余物通过硅胶快速柱色谱纯化(石油醚：乙酸乙酯＝10∶1用作洗脱剂)，纯化后，得到白色固体 2-甲基-5-(苯基(苯磺酰基)甲基)噻吩产率为82％。反应方程式如下所示。
Figure BDA0002382664790000031
产物2-甲基-5-(苯基(苯磺酰基)甲基)噻吩的结构表征数据如下：
1H NMR(400MHz,Chloroform-d)δ7.68–7.59(m,2H),7.58–7.45(m,3H),7.41–7.28(m, 5H),6.96(d,J＝3.5Hz,1H),6.62(dq,J＝3.4,1.1Hz,1H),5.45(s,1H),2.44(d,J＝1.1Hz,3H).
13C NMR(101MHz,CDCl3)δ142.08,137.54,133.79,133.56,132.68,130.95,130.21,129.98, 129.85,129.31,129.18,128.98,128.65,128.61,128.50,125.12,72.63,15.31.
HRMS(ESI):calculated for C18H16O2S2Na[M+Na]+＝351.0489,found C18H16O2S2Na[M+ Na]+＝351.0489.
Melting point:144-145℃.
实施例二
4-氟苯甲醛代替实施例一中的苯甲醛，得到白色固体2-((4-氟苯基)(苯磺酰基)甲基) -5-甲基噻吩的产率为89％。
1H NMR(400MHz,Chloroform-d)δ7.76–7.33(m,7H),7.12–6.87(m,3H),6.63(dq,J＝3.5, 1.1Hz,1H),5.44(s,1H),2.45(s,3H).
13C NMR(101MHz,cdcl3)δ164.23,161.75,142.17,137.30,133.68,131.82,131.74,130.71, 129.78,129.09,128.69,128.49,125.15,115.76,115.55,71.64,15.29.
HRMS(ESI):calculated for C18H15FO2S2Na[M+Na]+＝369.0395,foundC18H15FO2S2Na[M+ Na]+＝369.0373.
Melting point:129-130℃.
实施例三
2-氯苯甲醛代替实施例一中的苯甲醛，得到白色固体2-((2-氯苯基)(苯磺酰基)甲基) -5-甲基噻吩的产率为88％。
1H NMR(400MHz,Chloroform-d)δ8.23–8.16(m,1H),7.74–7.65(m,2H),7.63–7.55(m, 1H),7.47–7.35(m,3H),7.26–7.23(m,2H),7.00(d,J＝3.5Hz,1H),6.66(dd,J＝3.6,1.2Hz, 1H),6.29(s,1H),2.47(d,J＝1.1Hz,3H).
13C NMR(101MHz,CDCl3)δ142.43,137.63,134.73,133.77,130.99,130.70,130.26,130.13, 130.10,129.55,129.08,128.70,127.23,125.15,66.83,15.36.
HRMS(ESI):calculated for C18H15ClO2S2Na[M+Na]+＝385.0100,foundC18H15ClO2S2Na[M +Na]+＝385.0089.
Melting point:100-101℃.
实施例四
4-氯苯甲醛代替实施例一中的苯甲醛，得到白色固体2-((4-氯苯基)(苯磺酰基)甲基) -5-甲基噻吩的产率为88％。
1H NMR(400MHz,Chloroform-d)δ8.09–7.99(m,1H),7.68–7.61(m,2H),7.60–7.53(m, 1H),7.49–7.37(m,4H),7.31–7.28(m,1H),6.93(d,J＝3.5Hz,1H),6.62(dq,J＝3.4,1.1Hz, 1H),5.42(s,1H),2.44(d,J＝1.0Hz,3H).
13C NMR(101MHz,CDCl3)δ142.27,137.32,135.19,133.77,131.56,131.27,131.18,130.52, 129.87,129.16,128.89,128.87,128.76,125.20,71.80,15.31.
HRMS(ESI):calculated for C18H15ClO2S2Na[M+Na]+＝385.0100,foundC18H15ClO2S2Na[M +Na]+＝385.0089.
Melting point:125-126℃.
实施例五
2-溴苯甲醛代替实施例一中的苯甲醛，得到白色固体2-((2-溴苯基)(苯磺酰基)甲基) -5-甲基噻吩的产率为86％。
1H NMR(400MHz,Chloroform-d)δ8.22(dd,J＝7.9,1.6Hz,1H),7.77–7.64(m,2H),7.66– 7.53(m,1H),7.43(dddd,J＝10.8,8.3,5.0,2.2Hz,4H),7.18(td,J＝7.7,1.7Hz,1H),7.00(d,J＝3.5Hz,1H),6.66(dq,J＝3.4,1.1Hz,1H),6.31(s,1H),2.47(d,J＝1.1Hz,3H).
13C NMR(101MHz,CDCl3)δ142.46,137.64,133.81,132.95,132.73,130.75,130.36,130.21, 130.13,129.11,128.74,127.88,125.79,125.16,69.76,15.37.
HRMS(ESI):calculated for C18H15BrO2S2Na[M+Na]+＝428.9595,foundC18H15BrO2S2Na[M +Na]+＝428.9594.
Melting point:103-104℃.
实施例六
2-羟基苯甲醛代替实施例一中的苯甲醛，得到白色固体2-((5-甲基噻吩-2-基)(苯磺酰基) 甲基)苯酚的产率为77％。
1H NMR(400MHz,Chloroform-d)δ7.77–7.68(m,2H),7.67–7.53(m,3H),7.42(t,J＝7.8 Hz,2H),7.21(td,J＝7.8,1.7Hz,1H),7.02(d,J＝3.5Hz,1H),6.95(td,J＝7.6,1.2Hz,1H),6.82 (dd,J＝8.1,1.2Hz,1H),6.64(dd,J＝3.6,1.2Hz,1H),6.10(s,1H),2.45(d,J＝1.0Hz,3H).
13C NMR(101MHz,cdcl3)δ154.15,142.06,137.15,133.74,130.58,130.37,130.35,130.27, 129.11,129.05,128.66,128.60,125.03,120.94,119.21,116.82,65.08,15.32.
HRMS(ESI):calculated for C18H16O3S2Na[M+Na]+＝367.0439,found C18H16O3S2Na[M+ Na]+＝367.0426.
Melting point:124-125℃.
实施例七
4-甲基苯甲醛代替实施例一中的苯甲醛，得到白色固体2-甲基-5-((苯磺酰基)(对甲苯基) 甲基)噻吩的产率为77％。
1H NMR(400MHz,Chloroform-d)δ7.69–7.58(m,2H),7.58–7.51(m,1H),7.38(dd,J＝8.1, 6.8Hz,4H),7.11(d,J＝7.9Hz,2H),6.93(d,J＝3.5Hz,1H),6.61(dt,J＝3.6,1.1Hz,1H),5.42(s, 1H),2.43(d,J＝1.0Hz,3H),2.32(s,3H).
13C NMR(101MHz,cdcl3)δ144.64,141.95,138.96,137.50,133.51,131.20,130.23,129.79, 129.71,129.49,129.34,129.20,129.15,128.57,126.49,125.04,72.27,21.20,15.32.
HRMS(ESI):calculated for C19H18O2S2Na[M+Na]+＝365.0646,found C19H18O2S2Na[M+Na]+＝365.0635.
Melting point:151-152℃.
实施例八
甲醛代替实施例一中的苯甲醛，得到白色固体2-甲基-5-((苯磺酰基)甲基)噻吩的产率为72％。
1H NMR(400MHz,Chloroform-d)δ7.83–7.69(m,2H),7.68–7.58(m,1H),7.49(t,J＝7.8 Hz,2H),6.65–6.51(m,2H),4.43(s,2H),2.43(d,J＝1.1Hz,3H).
实施例九
乙醛代替实施例一中的苯甲醛，得到白色固体2-甲基-5-(1-(苯磺酰基)乙基)噻吩的产率为74％。
1H NMR(400MHz,Chloroform-d)δ7.70–7.53(m,3H),7.50–7.37(m,2H),6.62–6.51(m, 2H),4.42(q,J＝7.1Hz,1H),2.43(d,J＝1.0Hz,3H),1.74(d,J＝7.2Hz,3H).
13C NMR(101MHz,CDCl3)δ141.51,136.41,133.66,133.00,129.29,129.00,128.69,128.58, 124.93,61.97,15.43,15.37.
HRMS(ESI):calculated for C13H14O2S2Na[M+Na]+＝289.0333,found C13H14O2S2Na[M+ Na]+＝289.0325.
Melting point:89-90℃.
实施例十
2-呋喃甲醛代替实施例一中的苯甲醛，得到白色固体2-((5-甲基噻吩-2-基)(苯磺酰基) 甲基)呋喃的产率为69％。
1H NMR(400MHz,Chloroform-d)δ7.66–7.54(m,3H),7.48–7.35(m,3H),6.96(d,J＝3.5 Hz,1H),6.65(dt,J＝3.6,1.2Hz,1H),6.52(d,J＝3.4Hz,1H),6.37(dd,J＝3.4,1.9Hz,1H),5.62 (s,1H),2.46(d,J＝1.0Hz,3H).
13C NMR(101MHz,CDCl3)δ145.45,143.45,142.61,136.98,133.81,130.52,129.31,128.66, 128.13,125.23,112.10,111.11,66.68,15.34.
HRMS(ESI):calculated for C16H14O3S2Na[M+Na]+＝341.0282,found C16H14O3S2Na[M+ Na]+＝341.0277.
Melt point:132-133℃；
实施例十一
3-噻吩甲醛代替实施例一中的苯甲醛，得到白色固体2-甲基-5-((苯磺酰基)(噻吩-3-基) 甲基)噻吩的产率为71％。
1H NMR(400MHz,Chloroform-d)δ7.65–7.58(m,2H),7.58–7.51(m,1H),7.43–7.36(m, 2H),7.34(dd,J＝3.0,1.4Hz,1H),7.31–7.27(m,1H),6.90(d,J＝3.5Hz,1H),6.62(dq,J＝3.5,1.2 Hz,1H),5.62(s,1H),2.45(d,J＝1.1Hz,3H).
13C NMR(101MHz,CDCl3)δ142.25,137.25,133.64,132.45,130.66,129.94,129.13,128.65, 128.43,126.58,126.09,125.17,68.13,15.38.
HRMS(ESI):calculated for C16H14O2S3Na[M+Na]+＝357.0054,found HRMS(ESI):calculated for HRMS(ESI):calculated for C16H14O2S3Na[M+Na]+＝357.0036.
Melt point:138-139℃；
实施例十二
2-氟苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-((((2-氟苯基)磺酰基) (苯基)甲基)-5-甲基噻吩的产率为84％。
1H NMR(400MHz,Chloroform-d)δ7.68–7.56(m,3H),7.53–7.46(m,1H),7.34–7.28(m, 3H),7.19–7.07(m,2H),7.03(d,J＝3.5Hz,1H),6.60(dq,J＝3.4,1.1Hz,1H),5.86(s,1H),2.42 (d,J＝1.1Hz,3H).
13C NMR(101MHz,cdcl3)δ142.33,135.97,135.88,133.75,131.93,131.57,130.16,129.94, 129.85,129.13,128.69,128.48,125.16,124.40(d,J＝3.6Hz),116.58(d,J＝21.7Hz),71.53, 15.30.
HRMS(ESI):calculated for C18H15FO2S2Na[M+Na]+＝369.0395,foundC18H15FO2S2Na[M+ Na]+＝369.0371.
Melting point:127-128℃.
实施例十三
4-三氟甲基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-甲基-5-(苯基(((4- (三氟甲基)苯基)磺酰基)甲基)噻吩的产率为87％。
1H NMR(400MHz,Chloroform-d)δ7.75(d,J＝8.2Hz,2H),7.64(d,J＝8.2Hz,2H),7.56– 7.44(m,2H),7.40–7.28(m,3H),6.98(d,J＝3.6Hz,1H),6.64(dd,J＝3.5,1.2Hz,1H),5.47(s,1H), 2.45(d,J＝1.0Hz,3H).
13C NMR(101MHz,cdcl3)δ142.55,141.16,135.28,131.92,130.14,130.08,129.96,129.74, 129.30,128.80,125.71,125.67,125.63,125.60,125.23,121.69,109.98,72.68,15.31.
HRMS(ESI):calculated for C19H15F3O2S2Na[M+Na]+＝419.0363,foundC19H15F3O2S2Na[M +Na]+＝419.0360.
Melting point:121-122℃.
实施例十四
4-氯苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到2-(((4-氯苯基)磺酰基)(苯基) 甲基)-5-甲基噻吩的产率为86％。
1H NMR(400MHz,Chloroform-d)δ7.64–7.45(m,5H),7.42–7.30(m,4H),6.98(d,J＝3.5 Hz,1H),6.64(dq,J＝3.4,1.1Hz,1H),5.43(s,1H),2.45(d,J＝1.1Hz,3H).
13C NMR(101MHz,cdcl3)δ171.51,142.32,140.34,135.95,133.78,132.26,130.58,130.48, 130.18,129.98,129.94,129.16,128.93,128.75,128.48,125.18,109.98,72.69,15.34.
HRMS(ESI):calculated for C18H15ClO2S2Na[M+Na]+＝385.0100,found HRMS(ESI): calculated for HRMS(ESI):calculated for C18H15ClO2S2Na[M+Na]+＝385.0076.
Melting point:154-155℃.
实施例十五
3-氟苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-(((3-氟苯基)磺酰基) (苯基)甲基)-5-甲基噻吩的产率为80％。
1H NMR(400MHz,Chloroform-d)δ7.68-7.46(m,3H),7.45–7.29(m,5H),7.26–7.20(m, 1H),6.99(d,J＝3.5Hz,1H),6.64(dq,J＝3.4,1.1Hz,1H),5.46(s,1H),2.45(d,J＝1.1Hz,3H).
13C NMR(101MHz,Chloroform-d)δ162.00(d,J＝251.9Hz),142.38,133.75,132.16,130.38, 130.31,130.17,130.03,129.92,129.20,129.14,128.74,128.48,125.19,124.98,124.94,120.85(d,J ＝21.1Hz),116.46(d,J＝24.4Hz),72.62,15.32.
HRMS(ESI):calculated for C18H15FO2S2Na[M+Na]+＝369.0395,foundC18H15FO2S2Na[M+ Na]+＝369.0371.
Melting point:127-128℃.
实施例十六
4-叔丁基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-((((4-(叔丁基) 苯基)磺酰基)(苯基)甲基)-5-甲基噻吩的产率为75％。
1H NMR(400MHz,Chloroform-d)δ7.55–7.44(m,4H),7.40–7.34(m,2H),7.33–7.27(m, 3H),6.96(d,J＝3.5Hz,1H),6.62(dq,J＝3.5,1.1Hz,1H),5.42(s,1H),2.44(d,J＝1.1Hz,3H).
13C NMR(101MHz,cdcl3)δ157.52,141.92,134.37,133.78,132.84,131.14,130.18,129.93, 129.71,129.13,128.99,128.85,128.52,128.48,125.71,125.55,125.03,72.61,35.16,31.05,30.99, 15.30.
HRMS(ESI):calculated for C22H24O2S2Na[M+Na]+＝407.1115,found C22H24O2S2Na[M+ Na]+＝407.1110.
Melting point:154-155℃.
实施例十七
4-甲基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-甲基-5-(苯基(甲苯磺酰基)甲基)噻吩的产率为76％。
1H NMR(400MHz,Chloroform-d):δ7.45–7.37(m,4H),7.24(dt,J＝5.4,2.7Hz,3H),7.09 (d,J＝8.0Hz,2H),6.89(d,J＝3.5Hz,1H),6.55(dd,J＝3.5,1.3Hz,1H),5.35(s,1H)2.37(d,J＝ 1.1Hz,3H),2.31(s,3H).
13C NMR(101MHz,cdcl3)δ144.53,141.95,134.46,133.75,132.79,131.12,130.17,129.92, 129.73,129.24,129.16,128.88,128.59,128.48,125.05,72.54,21.65,15.33.
HRMS(ESI):calculated for C19H18O2S2Na[M+Na]+＝365.0646,found HRMS(ESI):calculated for HRMS(ESI):calculated for C19H18O2S2Na[M+Na]+＝365.0624.
Melting point:153-154℃.
实施例十八
甲基亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-甲基-5-((甲基磺酰基)(苯基)甲基)噻吩的产率为71％。
1H NMR(400MHz,Chloroform-d)δ7.72–7.58(m,2H),7.51–7.35(m,3H),7.12(d,J＝3.5 Hz,1H),6.70(dd,J＝3.5,1.2Hz,1H),5.47(s,1H),2.79(s,3H),2.47(d,J＝1.1Hz,3H).
13C NMR(101MHz,CDCl3)δ142.30,132.39,130.86,129.69,129.54,129.35,129.09,125.43, 70.83,39.15,15.35.
HRMS(ESI):calculated for C13H14O2S2Na[M+Na]+＝289.0333,found C13H14O2S2Na[M+ Na]+＝289.0316.
Melting point:129-130℃.
实施例十九
乙基亚磺酸钠代替实施例一中的苯亚磺酸钠，得到白色固体2-((乙基磺酰基)(苯基)甲基)-5-甲基噻吩的产率为72％。
1H NMR(400MHz,Chloroform-d)δ7.69–7.61(m,2H),7.46–7.36(m,3H),7.11(d,J＝3.5 Hz,1H),6.69(dq,J＝3.5,1.2Hz,1H),5.47(s,1H),2.90(qd,J＝7.5,1.7Hz,2H),2.46(d,J＝1.1 Hz,3H),1.34(t,J＝7.5Hz,3H).
13C NMR(101MHz,CDCl3)δ142.19,132.30,130.87,130.18,129.72,129.39,129.24,129.04, 128.51,125.39,68.34,45.67,15.34,6.75.
HRMS(ESI):calculated for C14H16O2S2Na[M+Na]+＝303.0489,found HRMS(ESI):calculated for HRMS(ESI):calculated for C14H16O2S2Na[M+Na]+＝303.0477.
实施例二十
2-乙基噻吩代替实施例一中的2-甲基噻吩，得到白色固体2-乙基-5-(苯基(苯磺酰基) 甲基)噻吩的产率为74％。
1H NMR(400MHz,Chloroform-d)δ8.16–8.08(m,1H),7.68–7.47(m,5H),7.43–7.31(m, 4H),7.02(d,J＝3.5Hz,1H),6.68(dt,J＝3.6,1.1Hz,1H),5.47(s,1H),2.92–2.75(m,2H),1.29(t, J＝7.5Hz,3H).
13C NMR(101MHz,cdcl3)δ149.72,137.44,133.73,133.54,132.59,130.41,130.16,129.96, 129.64,129.12,128.96,128.62,128.57,128.48,123.25,72.62,23.43,15.76.
HRMS(ESI):calculated for C19H18O2S2Na[M+Na]+＝365.0646,found C19H18O2S2Na[M+ Na]+＝365.0639.
Melting point:136-137℃.
实施例二十一
2-羟乙基噻吩代替实施例一中的2-甲基噻吩，得到白色固体2-(5-(苯基(苯磺酰基)甲基)噻吩-2-基)乙-1-醇的产率为72％。
1H NMR(400MHz,Chloroform-d)δ7.61(dd,J＝8.3,1.3Hz,2H),7.58–7.44(m,3H),7.37 (t,J＝7.8Hz,2H),7.34–7.26(m,3H),7.07(d,J＝3.6Hz,1H),6.75(d,J＝3.6Hz,1H),5.46(s, 1H),3.81(t,J＝6.3Hz,2H),3.01(t,J＝6.2Hz,2H).
13C NMR(101MHz,CDCl3)δ143.18,137.40,133.67,132.49,131.92,129.97,129.91,129.15, 129.09,128.71,128.66,125.64,72.54,63.23,33.48.
HRMS(ESI):calculated for C19H18O3S2Na[M+Na]+＝381.0595,found HRMS(ESI):calculated for HRMS(ESI):calculated for C19H18O3S2Na[M+Na]+＝381.0569.
Melting point:147-148℃.
实施例二十二
2-硫代甲基噻吩代替实施例一中的2-甲基噻吩，得到白色固体2-(甲硫基)-5-(苯基(苯磺酰基)甲基)噻吩的产率为79％。
1H NMR(400MHz,Chloroform-d)δ7.65–7.59(m,2H),7.54(ddt,J＝8.8,7.1,1.3Hz,1H), 7.49–7.44(m,2H),7.42–7.35(m,2H),7.34–7.27(m,3H),7.04(dd,J＝3.7,0.7Hz,1H),6.92(d, J＝3.7Hz,1H),5.44(s,1H),2.47(s,3H).
13C NMR(101MHz,CDCl3)δ139.77,137.28,135.36,133.75,132.20,130.25,130.17,129.96, 129.19,129.17,128.77,128.72,72.61,21.85.
HRMS(ESI):calculated for C18H16O2S3Na[M+Na]+＝383.0210,found 383.0198.
Melting point:128-129℃.
实施例二十三
噻吩代替实施例一中的2-甲基噻吩，得到白色固体2-(苯基(苯磺酰基)甲基)噻吩的产率为70％。
1H NMR(400MHz,Chloroform-d)δ7.66–7.58(m,2H),7.58–7.45(m,3H),7.42–7.23(m,6H), 7.23(dt,J＝3.6,1.0Hz,1H),6.99(dd,J＝5.2,3.6Hz,1H),5.54(s,1H).
实施例二十四
2-甲基呋喃代替实施例一中的2-甲基噻吩，得到白色固体2-甲基-5-(苯基(苯磺酰基) 甲基)呋喃的产率为69％。
1H NMR(400MHz,Chloroform-d)δ7.66–7.28(m,10H),6.43(d,J＝3.2Hz,1H),5.95(dd,J ＝3.2,1.1Hz,1H),5.36(s,1H),2.22(d,J＝1.0Hz,3H).
13C NMR(101MHz,CDCl3)δ153.39,143.55,137.71,133.78,133.61,130.75,130.42,130.20, 129.87,129.27,129.02,128.69,128.55,128.51,112.97,107.13,71.07,13.62.
HRMS(ESI):calculated for C18H16O3SNa[M+Na]+＝335.0718,found 335.0695.
Melting point:137-138℃.
实施例二十五
2-乙基呋喃代替实施例一中的2-甲基噻吩，得到白色固体2-乙基-5-(苯基(苯磺酰基) 甲基)呋喃的产率为67％。
1H NMR(400MHz,Chloroform-d)δ7.64–7.51(m,3H),7.54–7.45(m,2H),7.48–7.30(m, 5H),7.26(s,1H),6.45(d,J＝3.2Hz,1H),5.96(dt,J＝3.3,1.1Hz,1H),5.37(s,1H),2.56(qd,J＝ 7.6,1.0Hz,2H),1.15(t,J＝7.5Hz,3H).
13C NMR(101MHz,CDCl3)δ207.19,158.96,143.49,137.75,133.59,130.75,130.45,130.15, 129.25,129.01,128.57,128.55,128.48,112.75,105.57,71.10,21.35,12.07.
HRMS(ESI):calculated for C19H18O3SNa[M+Na]+＝349.0874,found 349.0857.
Melting point:126-127℃.
实施例二十六
苯并呋喃代替实施例一中的2-甲基噻吩，得到白色固体2-(苯基(苯磺酰基)甲基)苯并呋喃的产率为66％。
1H NMR(400MHz,Chloroform-d)δ7.72–7.52(m,5H),7.48–7.22(m,9H),7.03(s,1H), 5.57(s,1H).
13C NMR(101MHz,cdcl3)δ154.95,148.44,137.33,133.89,130.43,130.24,129.29,129.24, 128.71,128.67,127.75,124.90,123.11,121.32,111.32,108.64,71.21.
HRMS(ESI):calculated for C21H16O3SNa[M+Na]+＝371.0718,found C21H16O3SNa[M+ Na]+＝371.0707.
Melting point:164-165℃.
实施例二十七
硒吩代替实施例一中的2-甲基噻吩，得到白色固体2-(苯基(苯磺酰基)甲基)硒吩的产率为67％。
1H NMR(400MHz,Chloroform-d)δ7.97(dd,J＝5.6,1.2Hz,1H),7.61–7.53(m,2H),7.53– 7.38(m,3H),7.36–7.21(m,6H),7.12(dd,J＝5.7,3.8Hz,1H),5.53(s,1H).
13C NMR(101MHz,CDCl3)δ139.78,137.34,133.68,133.40,133.05,132.36,129.91,129.23, 129.12,128.97,128.77,128.67,74.40.
HRMS(ESI):calculated for C17H14O2SSeNa[M+Na]+＝384.9777,foundC17H14O2SSeNa[M +Na]+＝384.9772.
Melting point:161-162℃.

Claims (1)

1.一种芳基（硫属杂芳基）甲基砜的合成方法，其特征在于：在催化剂量的硫酸催化下，醛、烃基亚磺酸钠和硫属杂环化合物在水中60℃下进行三组分反应合成芳基（硫属杂芳基）甲基砜；所述的醛为苯甲醛、4-氟苯甲醛、2-氯苯甲醛、4-氯苯甲醛、2-溴苯甲醛、4-甲基苯甲醛、2-羟基苯甲醛；所述的烃基亚磺酸钠为苯亚磺酸钠、2-氟苯亚磺酸钠、3-氟苯亚磺酸钠、4-氯苯亚磺酸钠、4-甲基苯亚磺酸钠、4-三氟甲基苯亚磺酸钠、4-叔丁基苯亚磺酸钠、甲基亚磺酸钠、乙基亚磺酸钠；所述的硫属杂环化合物为2-甲基噻吩、2-乙基噻吩、2-羟乙基噻吩、2-硫代甲基噻吩、噻吩、2-甲基呋喃、2-乙基呋喃、苯并呋喃、硒吩。
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