阅读说明：本技术 一种二芳甲基烃基砜的合成方法 (A kind of synthetic method of two arylmethyls alkyl sulfone ) 是由 曾庆乐 库楚酷拉·拉纳卡·雷德 郑文婷 于 2019-09-25 设计创作，主要内容包括：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。(Sulfone is important drug and bioactive compound.Now very popular herbicide mesotrione and bioactive compound (such as inhibitors of gamma-secretase) belongs to sulfone compound.In addition, the drug of sulfone class can prevent Alzheimer's disease.Sulfone compound is also widely used as the intermediate of organic synthesis.In sulfone compound, two arylmethyl alkyl sulfones are the important starting materials for synthesizing triarylmethane, as leuco dye, photochromic agent, the structural unit for generating dendritic and for theoretical and biological study substrate, it is had received widespread attention.This patent develops a kind of three component reactions of recyclable ion-exchange resin catalyst Amberlyst-15 catalysis, and two arylmethyl alkyl sulfones are synthesized in extensive substrate spectrum with good yield and excellent yield.With the aryl groups per alkyl group aldehyde being easy to get, aryl groups per alkyl group sulfinic acid sodium and Polymethoxylated benzene are two arylmethyl alkyl sulfone of raw material one pot process, prepare two arylmethyl alkyl sulfones by the formation of C-C and C-S key.The advantages that synthesis technology has reaction condition especially mild, easy to operate, and yield is generally higher and substrate spectrum is wide.)

1. a kind of synthetic method of two arylmethyl alkyl sulfones, it is characterised in that: in the ion-exchange resin catalyst of catalytic amount Under the catalysis of Amberlyst-15, it is anti-that aldehyde, alkyl sulfinic acid sodium and Polymethoxylated benzene carry out three components at a temperature of 60 DEG C in water Answer synthesis of diaryl methyl sulfone.

2. a kind of synthetic method of two arylmethyls alkyl sulfone described in claim 1, it is characterised in that described aldehyde be benzaldehyde, 4- fluorobenzaldehyde, 4- chlorobenzaldehyde, 4- nitrobenzaldehyde, Benzaldehyde,2-methoxy, Benzaldehyde,2-hydroxy, 2- pyridine carboxaldehyde, benzene Acetaldehyde, formaldehyde, acetaldehyde.

3. a kind of synthetic method of two arylmethyls alkyl sulfone described in claim 1, it is characterised in that described alkyl sulfinic acid Sodium is benzene sulfinic acid sodium salt, 4- methyl sodium benzene sulphinate, 4- chlorobenzene sulfinic acid sodium, 4- bromine benzene sulfinic acid sodium salt, 4- methoxybenzene Asia sulphur Sour sodium, 4- tert-butyl benzene sulfinic acid sodium salt, tert-butyl sulfinic acid sodium.

4. a kind of synthetic method of two arylmethyls alkyl sulfone described in claim 1, it is characterised in that described Polymethoxylated benzene For 1,3,5- trimethoxy-benzene, 1,2,4- trimethoxy-benzene.

5. a kind of synthetic method of two arylmethyls alkyl sulfone described in claim 1, it is characterised in that described catalytic amount refers to Be the mass ratio of Amberlyst-15 and Polymethoxylated benzene be 0.5.

Technical field

The patent be related to organic synthesis, pharmaceutical synthesis, organic chemical industry research field, specific method is exactly alkyl Asia sulphur Sour sodium, aryl groups per alkyl group aldehyde and Polymethoxylated benzene carry out three component reaction one-step synthesis, two arylmethyl alkyl sulfone compound.

Background technique

Sulfone is important drug and bioactive compound.Now very popular herbicide mesotrione and biology is living Property compound (such as inhibitors of gamma-secretase) belongs to sulfone compound (D.Cornes, Patent:WO 2002/ 100173.R.A.Wichert and T.H.Beckett,WO 2002/019823.).In addition, the drug of sulfone class can prevent Ah Er Cihai Mo's disease (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.)。

They be also widely used as in organic synthesis important intermediate (M.Nambo, Z.T.Ariki, D.C.Gonzalez,D.D. Beattie and C.M.Crudden,Org.Lett.,2016,18,2339.).Wherein diaryl Sulfone as leuco dye (R.Muthyala, in:Chemistry and Applications of Leuco Dyes (Eds.: A.R.Katrizky, G.J.Sabongi), Plenum, New York, 1997.), photochromic agent (D.F.Duxbury, Chem.Rev.,1993,93,381；R.Aldag,in:Photochroism: Molecules and Systems(Eds.:H.D ü rr, H.Bouas-Laurent), Elsevier, London, 1990.), generate the structural unit of dendritic (L.A.Baker, L.Sun and R.M.Crooks, Bull.Korean Chem.Soc., 2002,23,647.) and for managing By (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.) and biological study (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., substrate 2004,14,347.), it has received widespread attention.

Report about two arylmethyl alkyl sulfones is seldom, mainly include the following types: (1) is in FeCl₃In the presence of, pass through α-acyl The arylation reaction of amido sulfone synthesize two arylmethyl alkyl sulfones (P.Thirupathi and S.S.Kim, Eur.J.Org.Chem.,2010,2010, 1798.).(2) in the presence of palladium catalyst, pass through the arylation of methylbenzene sulfone It is made two arylmethyl alkyl sulfones (M.Nambo and C.M.Crudden, Angew.Chem.Int.Ed., 2014,53,742.). (3) in the presence of iron (III) phthalocyanine-iron chloride by sulphonyl hydrazone synthesize sulfone (J.L.Zhao, S.H.Guo, J.Qiu, X.F.Gou, C.W.Hua and B.Chen,Tetrahedron Lett., 2016,57,2375.).(4) by quinone methides and sulphur 1,6- conjugate addition/aromatisation of hydrazides/two arylmethyl alkyl sulfones of sulfonylation preparation (T.Liu, J.Liu, S.Xia, J.Meng,X.Shen,X.Zhu,W.Chen,C.Sun and F.Cheng,ACS Omega,2018,3,1409.).However, In In all previous reports, the reaction of two steps is directed to synthesize two arylmethyl alkyl sulfones, i.e., aryl aldehyde is first by its turn Corresponding intermediate is turned to, two arylmethyl alkyl sulfones are then further converted in second step.

Therefore, to avoid using metallic catalyst, organic solvent and multistep reaction, we have developed a kind of two arylmethyl hydrocarbon The green synthesis method of base sulfone, i.e., in water, recyclable catalyst Amberlyst-15 are catalyzed aryl groups per alkyl group aldehyde, hydrocarbon Three component reactions of base sulfinic acid sodium and Polymethoxylated benzene synthesize two arylmethyl alkyl sulfones.

To the greatest extent known to us, document report same as the present application is had no.

Summary of the invention

The present invention provides a kind of synthetic method of two arylmethyl alkyl sulfones.

The uniform step of the synthetic method of two arylmethyls alkyl sulfone disclosed by the invention is completed, i.e., in water, Amberlyst-15 It is catalyzed aryl groups per alkyl group aldehyde, alkyl sulfinic acid sodium and Polymethoxylated benzene and three component reactions, two arylmethyl alkyl of one-step synthesis occurs Sulfone, reaction formula are as follows.Wherein, aryl groups per alkyl group aldehyde is alkyl aldehydes, aryl aldehyde and heteroaryl aldehyde.Polymethoxylated benzene is dimethoxy Base benzene and trimethoxy-benzene.Alkyl sulfinic acid sodium is sodium arylsulfinate and sodium alkyl-sulfinate.

In conjunction with the following examples, the present invention is explained in more detail, but is not regarded as that they are the limits to the scope of the invention System.

Specific embodiment