CN110511166A - 一种二芳甲基烃基砜的合成方法 - Google Patents

一种二芳甲基烃基砜的合成方法 Download PDF

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CN110511166A
CN110511166A CN201910910246.5A CN201910910246A CN110511166A CN 110511166 A CN110511166 A CN 110511166A CN 201910910246 A CN201910910246 A CN 201910910246A CN 110511166 A CN110511166 A CN 110511166A
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曾庆乐
库楚酷拉·拉纳卡·雷德
郑文婷
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Chengdu Univeristy of Technology
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Abstract

砜是重要的药物和生物活性化合物。现在广受欢迎的除草剂甲基磺草酮和生物活性化合物(例如γ‑分泌酶抑制剂)属于砜类化合物。此外，砜类的药物可以预防阿尔茨海默氏病。砜类化合物还被广泛用作有机合成的中间体。在砜类化合物中，二芳甲基烃基砜是合成三芳基甲烷的重要起始原料，作为无色染料、光致变色剂、生成树枝状聚合物的结构单元以及用于理论和生物学研究的底物，它受到了广泛的关注。本专利开发了一种可回收的离子交换树脂催化剂Amberlyst‑15催化的三组分反应，以良好的收率和优异的收率在广泛的底物范围内合成二芳甲基烃基砜。以容易获得的芳基/烷基醛，芳基/烷基亚磺酸钠和多甲氧基苯为原料一锅法合成二芳甲基烃基砜，通过C‑C和C‑S键的形成制备二芳甲基烃基砜。该合成工艺具有反应条件特别温和，操作简单，产率普遍较高，和底物范围广等优点。

Description

一种二芳甲基烃基砜的合成方法
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，具体的方法就是烃基亚磺酸钠、芳基/烷基醛和多甲氧基苯进行三组分反应一步合成二芳甲基烃基砜类化合物。
背景技术
砜是重要的药物和生物活性化合物。现在广受欢迎的除草剂甲基磺草酮和生物活性化合物 (例如γ-分泌酶抑制剂)属于砜类化合物(D.Cornes,Patent:WO 2002/100173.R.A.Wichert and T.H.Beckett,WO 2002/019823.)。此外，砜类的药物可以预防阿尔茨海默氏病(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 andJ.D.J.Wrigley,Bioorg.Med.Chem.Lett.,2006,16,280.)。
它们也被广泛用作有机合成中的重要中间体(M.Nambo,Z.T.Ariki,D.C.Gonzalez,D.D. Beattie and C.M.Crudden,Org.Lett.,2016,18,2339.)。其中二芳基砜作为无色染料(R.Muthyala, in:Chemistry and Applications of Leuco Dyes(Eds.:A.R.Katrizky,G.J.Sabongi),Plenum,New York,1997.)，光致变色剂(D.F.Duxbury,Chem.Rev.,1993,93,381；R.Aldag,in:Photochroism: Molecules and Systems(Eds.:H.Dürr,H.Bouas-Laurent),Elsevier,London,1990.)，生成树枝状聚合物的结构单元(L.A.Baker,L.Sun and R.M.Crooks,Bull.Korean Chem.Soc.,2002,23,647.)以及用于理论(M.S.Baptista and G.L.Indig,J.Phys.Chem.B 1998,102,4678；F.Terrier,T.Boubaker,L.Xiao and P.G.Farrell,J.Org.Chem.,1992,57,3924.)和生物学研究(M.R.Detty,S.L. Gibson and S.J.Wagner,J.Med.Chem.,2004,47,3897；M.Wainwright,D.Phoenix,A.S.M. Burrow and J.Waring,J.Chemother.,1999,11,61；R.A.Al-Qawasmeh,Y.Lee,M.-Y.Cao,X.Gu, A.Vassilakos,J.A.Wright and A.Young,Bioorg.Med.Chem.Lett.,2004,14,347.)的底物，它受到了广泛的关注。
关于二芳甲基烃基砜的报道很少，主要有以下几种：(1)在FeCl3存在下，通过α-酰胺基砜的芳基化反应合成二芳甲基烃基砜(P.Thirupathi and S.S.Kim,Eur.J.Org.Chem.,2010,2010, 1798.)。(2)在钯催化剂的存在下，通过甲基苯砜的芳基化制得二芳甲基烃基砜(M.Nambo and C.M.Crudden,Angew.Chem.Int.Ed.,2014,53,742.)。(3)在铁(III)酞菁-氯化铁存在下由磺酰腙合成砜(J.L.Zhao,S.H.Guo,J.Qiu,X.F.Gou,C.W.Hua and B.Chen,Tetrahedron Lett., 2016,57,2375.)。(4)通过对醌甲基化物与磺酰肼的1,6-共轭加成/芳构化/磺酰化反应制备二芳甲基烃基砜(T.Liu,J.Liu,S.Xia,J.Meng,X.Shen,X.Zhu,W.Chen,C.Sun and F.Cheng,ACS Omega,2018,3,1409.)。然而，在所有先前的报道中，都涉及两个步骤的反应来合成二芳甲基烃基砜，即芳基醛首先将其转化为相应的中间体，然后在第二步中将其进一步转化为二芳甲基烃基砜。
因此，为避免使用金属催化剂，有机溶剂和多步反应，我们开发了一种二芳甲基烃基砜的绿色合成方法，即在水中，可循环利用的催化剂Amberlyst-15催化芳基/烷基醛、烃基亚磺酸钠和多甲氧基苯的三组分反应合成二芳甲基烃基砜。
尽我们所知，未见与本申请相同的文献报道。
发明内容
本发明提供一种二芳甲基烃基砜的合成方法。
本发明公开的二芳甲基烃基砜的合成方法均一步完成，即在水中，Amberlyst-15催化芳基 /烷基醛、烃基亚磺酸钠和多甲氧基苯发生三组分反应，一步合成二芳甲基烃基砜，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。多甲氧基苯为二甲氧基苯和三甲氧基苯。烃基亚磺酸钠为芳基亚磺酸钠和烷基亚磺酸钠。
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
往烘干带磁力搅拌子的磨口试管里加入苯甲醛(1.5毫摩尔)、苯基亚磺酸钠(1.0毫摩尔)、 1,3,5-三甲氧基苯(1.0毫摩尔)、Amberlyst-15(相对于1,3,5-三甲氧基苯质量的50％)、水(1毫升)，最后用橡皮塞密封磨口试管。把该试管置于60℃油浴锅中搅拌反应6小时。然后向反应混合物中加入水(10mL)，将离子交换树脂过滤并用乙酸乙酯(5mL)洗涤3次。将滤液用乙酸乙酯(10mL)萃取3次，并将合并的有机层用无水MgSO4干燥，然后在旋转蒸发仪上在减压下吸附在一些硅胶上。将吸附了样品的硅胶转移到硅胶柱上。用硅胶柱色谱法(石油醚：乙酸乙酯＝5∶1作为洗脱剂)纯化后，得到白色固体1,3,5-三甲氧基-2-(苯基(苯基磺酰基) 甲基)苯产率为88％。反应方程式如下所示。
产物1,3,5-三甲氧基-2-(苯基(苯基磺酰基)甲基)苯的结构表征数据如下：
1H NMR(400MHz,CDCl3):δ＝7.69-7.63(m,2H),7.61-7.49(m,3H),7.45-7.24(m,5H),6.21 (s,1H),6.06(s,2H),3.80(s,3H),3.66(s,6H).
13C NMR(101MHz,CDCl3)δ161.72,141.02,134.19,132.64,130.18,128.67,128.15,127.91, 127.64,104.12,91.00,67.77,55.59,55.30.
HRMS(ESI):calculated for C22H22O5SNa[M+Na]+＝421.1086,found C22H22O5SNa[M+ Na]+＝421.1079.
Melting point:106-107℃.
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)(苯基磺酰基)甲基) -1,3,5-三甲氧基苯的产率为90％。
1H NMR(400MHz,DMSO-d6):δ7.70–7.60(m,1H),7.59–7.45(m,6H),7.20–7.08(m,2H),6.18(s,2H),6.09(s,1H),3.76(s,3H),3.62(s,6H)；
13C NMR(400MHz,DMSO-d6):δ167.99,166.74,165.56,145.29,138.48,137.31,137.23, 135.31,135.28,133.86,133.23,120.07,119.85,108.10,96.41,71.66,60.88,60.50.
HRMS(ESI):calculated for C22H21FO5SNa[M+Na]+＝439.0991,found C22H21FO5SNa[M+ Na]+＝439.0992.
Melting point:87-88℃.
实施例三
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)(苯基磺酰基)甲基) -1,3,5-三甲氧基苯的产率为91％。
1H NMR(400MHz,CDCl3):δ＝7.71-7.62(m,2H),7.59-7.49(m,3H),7.46-7.22(m,4H),6.14 (s,1H),6.05(s,2H),3.80(s,3H),3.64(s,6H).
13C NMR(101MHz,CDCl3)δ161.91,140.66,133.51,132.81,131.54,128.64,128.26,128.03, 103.50,91.00,66.83,55.59,55.31.
HRMS(ESI):calculated for C22H21ClO5SNa[M+Na]+＝455.0696,foundC22H21ClO5SNa[M +Na]+＝455.0696.
Melting point:118-119℃.
实施例四
4-硝基苯甲醛代替实施例一中的苯甲醛，得到白色固体1,3,5-三甲氧基-2-((4-硝基苯基) (苯基磺酰基)甲基)苯的产率为90％。
1H NMR(400MHz,CDCl3):δ8.06(d,J＝8.9Hz,2H),7.71(d,J＝8.7Hz,2H),7.59(d,J＝ 7.2Hz,2H),7.48(t,J＝7.4Hz,1H),7.34(t,J＝7.8Hz,2H),6.14(s,1H),5.93(s,2H),3.71(s,3H), 3.51(s,6H).
13C NMR(101MHz,CDCl3):δ162.34,146.96,142.16,140.09,133.15,130.79,128.72,128.35, 122.91,102.55,90.89,66.33,55.56,55.34.
HRMS(ESI):calculated for C22H21NO7SNa[M+Na]+＝466.0936,found C22H21NO7SNa[M+ Na]+＝466.0911.
Melting point:130-131℃.
实施例五
2-甲氧基苯甲醛代替实施例一中的苯甲醛，得到白色固体1,3,5-三甲氧基-2-((2-甲氧基苯基)(苯基磺酰基)甲基)苯的产率为70％。
1H NMR(400MHz,CDCl3):δ8.22(dd,J＝7.8,1.7Hz,1H),7.71–7.62(m,2H),7.53–7.44(m,1H),7.41–7.32(m,2H),7.20(ddd,J＝8.2,7.4,1.7Hz,1H),6.96(td,J＝7.6,1.2Hz,1H), 6.70(dd,J＝8.3,1.2Hz,1H),6.62(s,1H),6.01(s,2H),3.76(s,3H),3.60(s,6H),3.46(s,3H)；
13C NMR(101MHz,CDCl3):161.50,156.88,141.53,132.36,132.32,128.75,128.73,127.98, 122.59,119.99,110.25,104.01,91.22,59.89,55.72,55.36,55.22.
HRMS(ESI):calculated for C23H24O6SNa[M+Na]+＝451.1191,found C23H24O6SNa[M+ Na]+＝451.1193.
Melting point:150-151℃.
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-((苯基磺酰基)(2,4,6-三甲氧基苯基)甲基)苯酚的产率为75％。
1H NMR(400MHz,DMSO-d6)δ9.3(bs,1H),8.06(d,J＝7.9Hz,1H),7.55(td,J＝21.3,19.1, 7.4Hz,4H),7.32(d,J＝6.2Hz,1H),7.05(t,J＝7.7Hz,1H),6.77(t,J＝7.6Hz,1H),6.67(d,J＝ 8.0Hz,1H),6.53(s,1H),6.11(s,2H),3.73(s,3H),3.52(s,6H)；
13C NMR(101MHz,DMSO)δ161.70,155.61,148.72,141.20,133.42,132.66,128.90,128.90, 128.86,128.60,128.11,125.94,120.57,118.23,115.05,103.40,91.75,59.70,56.10,55.71.
HRMS(ESI):calculated for C23H24O6SNa[M+Na]+m/z＝437.1035,foundC23H24O6SNa[M +Na]+m/z＝437.1036.
Melting point:116-117℃.
实施例七
2-吡啶甲醛代替实施例一中的苯甲醛，得到白色固体-((苯基磺酰基)(2,4,6-三甲氧基苯基)甲基)吡啶的产率为75％。
1H NMR(400MHz,CDCl3):δ8.46(ddd,J＝4.9,1.9,0.9Hz,1H),8.07(dt,J＝8.0,1.1Hz, 1H),7.75–7.62(m,3H),7.56–7.46(m,1H),7.38(dd,J＝8.4,7.2Hz,2H),7.14(ddd,J＝7.6,4.9, 1.1Hz,1H),6.35(s,1H),5.98(s,2H),3.75(s,3H),3.50(s,6H).
13C NMR(101MHz,CDCl3):δ162.09,154.76,148.64,140.75,135.73,132.81,128.97,128.11, 125.09,122.18,102.75,90.98,68.64,55.54,55.27.
HRMS(ESI):calculated for C21H21NO5SNa[M+Na]+＝422.1038,found C21H21NO5SNa[M+ Na]+＝422.1039.
Melting point:130-131℃.
实施例八
苯乙醛代替实施例一中的苯甲醛，得到浅色固体1,3,5-三甲氧基-2-(2-苯基-1-(苯基磺酰基)乙基)苯的产率为70％。
1H NMR(400MHz,CDCl3):δ7.78–7.66(m,2H),7.54(t,J＝7.6Hz,1H),7.42(t,J＝7.6 Hz,2H),7.20–7.01(m,5H),6.00(d,J＝2.3Hz,1H),5.81(d,J＝2.3Hz,1H),5.27(dd,J＝11.6, 4.7Hz,1H),3.89(dd,J＝13.6,11.6Hz,1H),3.74(s,3H),3.67(s,4H),3.38(s,3H).
13C NMR(101MHz,CDCl3)δ161.59,160.78,159.85,139.83,138.45,132.71,128.93,128.67, 128.11,128.03,126.06,100.92,91.02,90.34,63.97,55.74,55.26,55.14,31.65.
HRMS(ESI):calculated for C23H24O5SNa[M+Na]+＝435.1242,found C22H21FO5SNa[M+ Na]+＝435.1242.
实施例九
甲醛代替实施例一中的苯甲醛，得到浅色固体1,3,5-三甲氧基-2-((苯基磺酰基)甲基) 苯的产率为82％。
1H NMR(400MHz,CDCl3):δ7.73–7.63(m,2H),7.59–7.47(m,1H),7.46–7.36(m,2H),5.96(s,2H),4.48(s,2H),3.76(s,3H),3.46(s,6H).
13C NMR(101MHz,CDCl3)δ161.88,159.58,140.16,132.80,128.63,128.19,98.11,90.16, 55.38,55.29,51.65.
HRMS(ESI):calculated for C16H18O5SNa[M+Na]+＝345.0773,found C16H18O5SNa[M+ Na]+＝345.0772.
实施例十
乙醛代替实施例一中的苯甲醛，得到浅色固体1,3,5-三甲氧基-2-(1-(苯基磺酰基)乙基) 苯的产率为79％。
1H NMR(400MHz,CDCl3)δ7.78–7.64(m,2H),7.62–7.48(m,1H),7.48–7.36(m,2H),6.00(dd,J＝36.1,2.3Hz,2H),5.06(q,J＝7.3Hz,1H),3.80(s,3H),3.55(d,J＝15.4Hz,6H),1.84 (d,J＝7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ161.54,161.15,159.23,139.50,132.62,129.06,128.04,103.04, 91.08,90.17,57.86,55.62,55.24,12.81.
HRMS(ESI):calculated for C17H20O5SNa[M+Na]+＝359.0929,found C17H20O5SNa[M+ Na]+＝359.0921.
Melt point:123-124℃；
实施例十一
4-氯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-氯苯基)磺酰基) (苯基)甲基)-1,3,5-三甲氧基苯的产率为90％。
1H NMR(400MHz,CDCl3):δ7.52–7.43(m,4H),7.31–7.25(m,2H),7.24–7.16(m,3H),6.08(s,1H),5.98(s,2H),3.72(s,3H),3.58(s,6H).
13C NMR(101MHz,CDCl3):δ161.85,139.54,139.21,133.89,130.19,130.15,128.38,128.00, 127.79,103.82,92.88,91.02,68.04,55.57,55.31.
HRMS(ESI):calculated for C22H21ClO5SNa[M+Na]+＝455.0696,foundC22H21ClO5SNa [M+Na]+＝455.0695.
Melting point:125-126℃.
实施例十二
4-溴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-溴苯基)磺酰基) (苯基)甲基)-1,3,5-三甲氧基苯的产率为80％。
1H NMR(400MHz,CDCl3)δ7.62–7.50(m,4H),7.53–7.45(m,2H),7.35–7.24(m,3H),6.17(s,1H),6.08(s,2H),3.81(s,3H),3.67(s,6H).
13C NMR(101MHz,CDCl3):δ161.90,159.63,140.10,134.49,131.42,130.34,130.19,129.76, 129.02,128.06,127.86,103.80,92.91,91.05,68.08,55.61,55.36.
HRMS(ESI):calculated for C22H21BrO5SNa[M+Na]+＝499.0191,foundC22H21BrO5SNa[M +Na]+＝499.0149.
Melting point:127-128℃.
实施例十三
4-甲基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到1,3,5-三甲氧基-2-(苯基(对甲苯磺酰基)甲基)苯的产率为79％。
1H NMR(400MHz,CDCl3):δ7.61–7.50(m,4H),7.33–7.25(m,3H),7.20(dd,J＝7.4,1.3 Hz,2H),6.18(s,1H),6.08(s,2H),3.80(s,3H),3.67(s,6H),2.40(s,3H).
13C NMR(101MHz,CDCl3):δ161.64,143.35,138.21,134.40,130.21,128.80,128.68,127.88, 127.58,104.34,91.05,67.80,55.61,55.30,21.51.
HRMS(ESI):calculated for C23H24O5SNa[M+Na]+＝435.1242,found C23H24O5SNa[M+ Na]+＝435.1228.
实施例十四
4-甲氧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1,3,5-三甲氧基-2-(((4- 甲氧基苯基)磺酰基)(苯基)甲基)苯的产率为75％。
1H NMR(400MHz,CDCl3):δ7.65–7.53(m,4H),7.33–7.22(m,3H),6.90–6.83(m,2H),6.17(s,1H),6.08(s,2H),3.83(d,J＝18.2Hz,6H),3.68(s,6H).
13C NMR(101MHz,CDCl3):δ162.95,161.65,161.53,134.52,134.50,132.84,130.83,130.23, 129.76,129.02,127.91,127.58,113.36,104.48,92.91,91.09,67.94,55.68,55.57,55.33.
HRMS(ESI):calculated for C23H24O6SNa[M+Na]+＝451.1191,found C23H24O6SNa[M+ Na]+＝451.1187.
Melting point:120-121℃.
实施例十五
4-叔丁基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到黄色固体2-(((4-(叔丁基)苯基)磺酰基)(苯基)甲基)-1,3,5-三甲氧基苯的产率为76％。
1H NMR(400MHz,CDCl3):δ7.58(ddt,J＝9.0,4.3,2.7Hz,4H),7.44–7.37(m,2H),7.35– 7.23(m,3H),6.19(s,1H),6.05(s,2H),3.80(s,3H),3.63(s,6H),1.34(s,9H).
13C NMR(101MHz,CDCl3):δ161.71,156.38,138.10,134.50,134.44,130.17,129.76,129.01, 128.55,128.45,127.87,127.53,125.59,125.15,104.34,92.91,91.02,67.59,55.60,55.34,55.32, 35.11,31.12,29.71.
HRMS(ESI):calculated for C26H30O5SNa[M+Na]+＝477.1712,found C26H30O5SNa[M+ Na]+＝477.1705.
Melting point:115-116℃.
实施例十六
叔丁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-((叔丁基磺酰基)(苯基)甲基)-1,3,5-三甲氧基苯的产率为75％。
1H NMR(400MHz,CDCl3):δ7.78–7.70(m,2H),7.26–7.11(m,3H),6.30(s,1H),6.05(t,J ＝1.9Hz,2H),3.83(s,3H),3.81(s,3H),3.70(s,3H),1.29(s,9H).
13C NMR(101MHz,CDCl3):δ161.35,160.29,157.84,137.12,130.36,128.02,127.51,105.97, 91.71,91.07,62.36,57.62,56.18,55.77,55.31,24.18.
HRMS(ESI):calculated for C20H26O5SNa[M+Na]+＝401.1399,found C20H26O5SNa[M+ Na]+＝401.1383.
Melting point:112-113℃.
实施例十七
1,2,4-三甲氧基苯代替实施例一中的1,3,5-三甲氧基苯，得到1,2,4-三甲氧基-5-(苯基(苯基磺酰基)甲基)苯的产率为80％。
1H NMR(400MHz,CDCl3):δ7.70–7.57(m,5H),7.56–7.50(m,1H),7.42–7.29(m,5H),6.32(s,1H),6.03(s,1H),3.94(s,3H),3.85(s,3H),3.51(s,3H)；
13C NMR(101MHz,CDCl3):δ151.64,149.97,143.14,138.84,133.34,133.16,129.99,128.86, 128.61,128.34,128.33,113.25,112.74,96.78,66.32,56.61,56.33,55.95.
HRMS(ESI):calculated for C22H22O5SNa[M+Na]+＝421.1086,found C22H22O5SNa[M+ Na]+＝421.1091.
实施例十八
1,3-二甲氧基苯代替实施例一中的1,3,5-三甲氧基苯，得到白色固体2,4-二甲氧基-1-(苯基(苯基磺酰基)甲基)苯的产率为69％。
1H NMR(400MHz,CDCl3):δ7.86(d,J＝8.7Hz,1H),7.59–7.52(m,2H),7.53–7.47(m,2H),7.47–7.40(m,1H),7.34–7.21(m,4H),7.19(s,1H),6.49(dd,J＝8.7,2.5Hz,1H),6.17(d,J ＝2.5Hz,1H),5.90(s,1H),3.71(s,3H),3.41(s,3H).
13C NMR(101MHz,CDCl3)δ160.95,157.86,138.92,133.45,133.09,130.88,130.10,128.94, 128.53,128.27,128.25,114.13,109.99,104.67,98.24,66.32,55.37,55.34.
Melting point:111-112℃.
实施例十九
4-氯苯甲醛代替实施例一中的苯甲醛，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-((4-氯苯基)(对甲苯磺酰基)甲基)-1,3,5-三甲氧基苯的产率为81％。
1H NMR(400MHz,CDCl3):δ7.61–7.47(m,4H),7.31–7.17(m,4H),6.11(s,1H),6.06(s, 2H),3.81(s,3H),3.76–3.54(s,6H),2.41(s,3H).
13C NMR(101MHz,CDCl3):δ161.81,143.59,137.87,133.46,133.01,131.55,128.90,128.66, 128.01,103.76,91.02,66.86,55.61,55.31,21.52.
HRMS(ESI):calculated for C23H23ClO5SNa[M+Na]+＝469.0852,foundC23H23ClO5SNa [M+Na]+＝469.0830.
Melting point:108-109℃.
实施例二十
4-硝基苯甲醛代替实施例一中的苯甲醛，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1,3,5-三甲氧基-2-((4-硝基苯基)(对甲苯磺酰基)甲基)苯的产率为86％。
1H NMR(400MHz,CDCl3):δ8.09–8.01(m,2H),7.76–7.65(m,2H),7.50–7.40(m,2H),7.13(d,J＝8.0Hz,2H),6.11(s,1H),5.94(s,2H),3.71(s,3H),3.52(s,6H),2.32(s,3H).
13C NMR(101MHz,CDCl3):δ162.25,146.93,144.03,142.37,137.25,130.83,128.99,128.72, 122.88,102.76,90.95,66.39,55.58,55.35,21.54.
HRMS(ESI):calculated for C23H23NO7SNa[M+Na]+＝480.1093,found C23H23NO7SNa[M +Na]+＝469.1061.
Melting point:133-134℃.
实施例二十一
2-吡啶甲醛代替实施例一中的苯甲醛，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-(甲苯磺酰基(2,4,6-三甲氧基苯基)甲基)吡啶的产率为72％。
1H NMR(400MHz,CDCl3):δ8.44(ddd,J＝4.9,1.9,1.0Hz,1H),8.08(dt,J＝8.1,1.1Hz, 1H),7.66(td,J＝7.8,1.9Hz,1H),7.61–7.54(m,2H),7.20–7.16(m,2H),7.13(ddd,J＝7.5,4.9, 1.1Hz,1H),6.32(s,1H),5.99(s,2H),3.76(s,3H),3.52(s,6H),2.37(s,3H).
13C NMR(101MHz,CDCl3):δ162.00,154.92,148.60,143.55,137.92,135.72,128.97,128.76, 125.15,122.14,102.97,91.02,68.71,55.55,55.28,21.51.
HRMS(ESI):calculated for C22H23NO5SNa[M+Na]+＝436.1195,found C22H23NO5SNa[M +Na]+＝436.1194.
Melting point:131-132℃.
实施例二十二
4-氯苯甲醛代替实施例一中的苯甲醛，4-氯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-氯苯基)((4-氯苯基)磺酰基)甲基)-1,3,5-三甲氧基苯的产率为93％。
1H NMR(400MHz,CDCl3):δ7.52–7.40(m,4H),7.33–7.25(m,2H),7.21–7.14(m,2H),6.01(s,1H),5.96(s,2H),3.71(s,3H),3.56(s,6H).
13C NMR(101MHz,CDCl3)δ162.03,139.47,139.15,133.70,132.48,131.48,130.16,129.32, 128.50,128.13,127.19,103.18,90.97,67.04,55.58,55.34.
HRMS(ESI):calculated for C22H20Cl2O5SNa[M+Na]+m/z＝489.0306,foundC22H20Cl2O5SNa[M+Na]+m/z＝489.0322.
Melting point:133-134℃.
实施例二十三
2-溴-5-甲氧基苯甲醛代替实施例一中的苯甲醛，4-氯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-溴-5-甲氧基苯基)((4-氯苯基)磺酰基)甲基)-1,3,5-三甲氧基苯的产率为71％。
1H NMR(400MHz,CDCl3):δ8.02(d,J＝3.1Hz,1H),7.61–7.45(m,2H),7.39–7.28(m,2H),7.28–7.14(m,1H),6.64(dd,J＝8.8,3.1Hz,1H),6.27(s,1H),5.96(s,2H),3.78(s,3H),3.72 (s,3H),3.56(s,6H).
13C NMR(101MHz,CDCl3)δ162.06,158.11,139.59,139.04,134.64,132.83,130.49,128.59, 118.51,115.97,115.54,102.34,91.05,66.20,55.57,55.47,55.28.
HRMS(ESI):calculated for C23H22BrClO6SNa[M+Na]+m/z＝562.9907,foundC22H20Cl2O5SNa[M+Na]+m/z＝562.9906.
Melting point:161-162℃.
实施例二十四
4-氯苯甲醛代替实施例一中的苯甲醛，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-((4-氯苯基)(乙基磺酰基)甲基)-1,3,5-三甲氧基苯的产率为75％。
1H NMR(400MHz,CDCl3):δ7.54–7.45(m,2H),7.24–7.17(m,2H),6.10(s,2H),6.05(s, 1H),3.75(s,3H),3.73(s,6H),2.88(ddq,J＝45.8,13.7,7.5Hz,2H),1.22(t,J＝7.5Hz,3H).
13C NMR(101MHz,CDCl3)δ161.91,133.80,132.53,131.11,128.37,103.49,91.36,65.15, 55.78,55.36,46.70,6.14.
HRMS(ESI):calculated for C18H21ClO5SNa[M+Na]+＝407.0696,foundC18H21ClO5SNa[M+Na]+＝407.0676.
Melting point:88-89℃.
实施例二十五
1,2,4-三甲氧基苯代替实施例一中的1,3,5-三甲氧基苯，4-甲基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到1,2,4-三甲氧基-5-(苯基(对甲苯磺酰基)甲基)苯的产率为80％。
1H NMR(400MHz,CDCl3):δ7.63–7.54(m,3H),7.54–7.48(m,2H),7.36–7.28(m,3H),7.16(d,J＝7.9Hz,2H),6.33(s,1H),5.98(s,1H),3.92(s,3H),3.84(s,3H),3.52(s,3H),2.37(s, 3H).
13C NMR(101MHz,CDCl3):δ151.66,149.89,144.00,143.18,135.98,133.54,130.01,128.97, 128.88,128.54,128.25,113.26,97.03,66.40,56.61,56.44,55.97,21.54.
HRMS(ESI):calculated for C23H24O5SNa[M+Na]+＝435.1242,found C23H24O5SNa[M+ Na]+＝435.1225.
实施例二十六
1,2,4-三甲氧基苯代替实施例一中的1,3,5-三甲氧基苯，4-硝基苯甲醛代替实施例一中的苯甲醛，得到白色固体1,2,4-三甲氧基-5-((4-硝基苯基)(苯基磺酰基)甲基)苯的产率为89％。
1H NMR(400MHz,CDCl3):δ8.20–8.12(m,2H),7.83–7.71(m,2H),7.68–7.58(m,2H),7.59–7.49(m,1H),7.43(s,1H),7.37(t,J＝7.8Hz,2H),6.27(s,1H),6.08(s,1H),3.88(s,3H), 3.81(s,3H),3.45(s,3H).
13C NMR(101MHz,CDCl3):δ151.66,150.53,147.60,143.32,140.85,138.28,133.65,130.88, 128.82,128.58,123.64,112.94,111.31,96.64,65.69,56.72,56.15,55.98.
HRMS(ESI):calculated for C22H20NO7S[M-H]+＝442.0955,found C22H20NO7S[M-H]+＝442.0951.
Melting point:160-161℃.
实施例二十七
1,2,4-三甲氧基苯代替实施例一中的1,3,5-三甲氧基苯，4-硝基苯甲醛代替实施例一中的苯甲醛，4-甲基苯亚磺酸钠代替实施例一中的苯亚磺酸钠，得到产物1,2,4-三甲氧基-5-((4- 硝基苯基)(对甲苯磺酰基)甲基)苯的产率为80％。
1H NMR(400MHz,CDCl3):δ8.21–8.09(m,2H),7.74(d,J＝8.8Hz,2H),7.53–7.48(m,2H),7.47(s,1H),7.21–7.13(m,2H),6.30(s,1H),6.04(s,1H),3.89(s,3H),3.82(s,3H),3.49(s, 3H),2.36(s,3H).
13C NMR(101MHz,CDCl3)δ151.67,150.42,147.57,144.68,143.33,141.06,135.39,130.89, 129.24,128.84,123.60,112.87,111.63,96.81,65.79,56.70,56.25,55.99,21.59.
HRMS(ESI):calculated for C23H22NO7S[M-H]+＝456.1111,found C22H20NO7S[M-H]+＝456.1114。

Claims (5)

1.一种二芳甲基烃基砜的合成方法，其特征在于：在催化剂量的离子交换树脂催化剂Amberlyst-15的催化下，醛、烃基亚磺酸钠和多甲氧基苯在水中60℃温度下进行三组分反应合成二芳基甲基砜。
2.权利要求1所述的一种二芳甲基烃基砜的合成方法，其特征在于所说的醛为苯甲醛、4-氟苯甲醛、4-氯苯甲醛、4-硝基苯甲醛、2-甲氧基苯甲醛、2-羟基苯甲醛、2-吡啶甲醛、苯乙醛、甲醛、乙醛。
3.权利要求1所述的一种二芳甲基烃基砜的合成方法，其特征在于所说的烃基亚磺酸钠为苯亚磺酸钠、4-甲基苯亚磺酸钠、4-氯苯亚磺酸钠、4-溴苯亚磺酸钠、4-甲氧基苯亚磺酸钠、4-叔丁基苯亚磺酸钠、叔丁基亚磺酸钠。
4.权利要求1所述的一种二芳甲基烃基砜的合成方法，其特征在于所说的多甲氧基苯为1,3,5-三甲氧基苯、1,2,4-三甲氧基苯。
5.权利要求1所述的一种二芳甲基烃基砜的合成方法，其特征在于所说的催化剂量指的是Amberlyst-15和多甲氧基苯的质量比是0.5。
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CN113230239B (zh) * 2021-01-29 2023-08-29 江西亿森傲游医药科技有限公司 一种用于治疗阿尔兹海默症的学习记忆能力药物的用途

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