A method for preparing benzothiophene sulfone compounds with pharmaceutical and fluorescent activity

Abstract

This invention provides a method for preparing 2-alkylthiobenzo[b]thiophene sulfone compounds. Using acylsulfonylmethylthio ylide compounds as raw materials, cyclization in the presence of an acid anhydride or acyl halide is induced to achieve the preparation of 2-alkylthiobenzo[b]thiophene sulfone compounds. This preparation method uses readily available and simple raw materials and is easy to operate. The obtained compounds can be applied to important organic materials, such as luminescent materials, antibacterial and anticancer drugs, and pesticides. They can also be used as intermediates in the synthesis of organic materials and drugs, and for the preparation of various materials and drugs.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing benzothiophene sulfone compounds. Background Technology

[0002] Benzo[b]thiophene sulfones, especially benzo[b]thiophene sulfones, are an important class of sulfur-containing heterocyclic compounds that can be used as antibacterial agents, exhibiting good inhibitory effects against both bacteria and fungi (Relyea, DIDE 2002800, 1970-07-30; Li, WZ; Xi, HZ; Wang, YJ; Ma, HB; Cheng, ZQ; Yang, Y.; Wu, ML; Liu, TM; Yang, W.; Wang, Q.; Liao, MY; Xia, Y.; Zhang, YW; Chem. Biol. Drug). Des.2021,98,835-849;Kummari,LK;Butler,MS;Furlong,E.;Blundell,R.;Nouwens,A.;Silva,AB;Kappler,U.;Fraser,JA;Kobe,B.;Cooper,MA;Robertson,AABBioorg.Med.Chem.2018 , 26, 5408-5419), and can also be used in anticancer drugs (Zhang, W.; Ma, T.; Li, S.; Yang, Y.; Guo, J.; Yu, W.; Kong, L. Eur. J.Med.Chem.2017,125,538-550; Ji, P.; Xu, X.; Ma, S.; Fan, J.; Zhou, Q.; Mao, X.; Qiao, C.ACS Med.Chem.Lett.2015,6,1010-1014;Chen,H.;Yang,Z.;Ding,C.;Xiong,A.;Wild,C.;Wang,L.;Ye,N.;Cai,G.;Flores,RM;Ding,Y .;Shen, Q.; Zhou, J. Eur. J. Med. Chem. 2014, 82, 195-203; Chen, H.; Yang, Z.; Ding, C.; Chu, L.; Zhang, Y.; Terry, K.; Liu, H.; Shen, Q.; Zhou, J. Eur. J. Med. Chem. 2013, 62, 498-507.), can also be used as a luminescent material (Guo, J.; Hu, S.; Luo, W.; Hu, R.; Qin, A.; Zhao, Z.; Tang, BZA Chem. Commun. 2017, 53, 1463-1466; Chen, S.; Chen, LJ; Yang, HB; Tian, ​​H.; Zhu, WJA M. Chem. Soc. 2012, 134, 13596-13599; Chen, S.; Yang, Y.(Wu, Y.; Tian, ​​H.; Zhu, WJ Mater. Chem. 2012, 22, 5486-5494.). Furthermore, benzo[b]thiophene sulfones are important organic synthetic intermediates with wide applications in medicinal chemistry, pesticides, and synthetic chemistry.

[0003] Because benzo[b]thiophene sulfones have wide applications in pharmaceuticals and organic synthesis of materials, several preparation methods have been developed. Benzo[b]thiophene sulfones are prepared via a [4+1] cyclization reaction of o-alkynylarylboronic acid or diazonium salt with sulfur dioxide (DABCO) complexes (Mao, R.; Zheng, DQ; Xia, HG; Wu, J. Org. Chem. Front. 2016, 3, 693-696; Luo, Y.; Pan, X.; Chen, C.; Yao, L.; Wu, J. Chem. Commun. 2015, 51, 180-182). Benzo[b]thiophene sulfones are prepared via a [3+2] cyclization reaction of arylsulfonyl hydrazine with diarylalkynyl hydrazine (Ma, Y.; Wang, K.; Zhang, D.; Su...). (n, P. Adv. Syn. Catal. 2019, 361, 597-602). This reaction can also be achieved via electrochemical reactions, extending the alkyne range to aliphatic alkynes (Li, R.; Yuan, D.; Ping, M.; Zhu, Y.; Ni, S.; Li, M.; Wen, L.; Zhang, L B Chem. Sci. 2022, 13, 9940-9946), and synthesizing benzo[b]thiophene sulfones via silver-catalyzed oxidative functionalization (Chen, YR; Duan, WL J Am. Chem. Soc. 2013, 135, 16754–16757.). These methods all have limited substrate applicability and are difficult to synthesize structurally diverse benzo[b]thiophene sulfones, especially 2-alkylthiobenzo[b]thiophene sulfones.

[0004] This invention uses readily available acylsulfonylmethylthioylide as a starting material to induce a cyclization reaction in the presence of a base via an acid anhydride or acyl halide to yield 2-alkylthiobenzo[b]thiophene sulfone compounds. The reactants are simple and readily available, and the process is easy to operate. The obtained compounds can be applied in many fields, including important organic synthesis intermediates, organic materials, pharmaceuticals, and pesticides. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing 2-alkylthiobenzo[b]thiophene sulfone compounds. These compounds can be used as important organic materials, pharmaceuticals, and pesticides, and can also be used as intermediates in the synthesis of organic materials, pharmaceuticals, and pesticides, for the preparation of various materials, pharmaceuticals, and pesticides. The preparation method of the compounds of this invention uses acylsulfonylmethylthioylide as a raw material. The raw material is simple and readily available, and does not require cumbersome operations, making it a simple method suitable for large-scale preparation.

[0006] The technical solution of the present invention is as follows:

[0007] Acylsulfonylmethylthioylide compounds (Formula 1) are cyclized in the presence of a base via acid anhydride or acyl halide to prepare 2-alkylthiobenzo[b]thiophene sulfone compounds (Formula 2).

[0008]

[0009] In the above reaction formula:

[0010] R 1 R 2 R 3 and R 4 This indicates alkyl groups having 1 to 6 carbon atoms, cycloalkyl groups having 3 to 6 carbon atoms, and R. 1 R 2 and R 3 An aryl group having 6 to 12 carbon atoms, which may contain alkyl, fluorine, chlorine, bromine, cyano, nitro, or dimethylamino groups as substituents; R 1 It can also be hydrogen, halogen, alkoxy group with 1 to 6 carbon atoms, alkynyl group with 3 to 9 carbon atoms, or ester group with 2 to 6 carbon atoms; R 1 R 2 R 3 and R 4 They can be the same or different.

[0011] The alkyl group referred to therein refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, isopentyl, sec-pentyl, neopentyl, hexyl, isohexyl, and particularly preferred are straight-chain or branched alkyl groups having 1 to 3 carbon atoms, with methyl and ethyl being the most preferred.

[0012] The cycloalkyl group refers to a cycloalkyl group having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, methylcyclopentyl, and dimethylcyclopropyl.

[0013] The aryl group refers to an aryl group having 6 to 12 carbon atoms. Preferably, it is phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-ethylphenyl, m-ethylphenyl, p-ethylphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-ethoxyphenyl, m-ethoxyphenyl, p-ethoxyphenyl, 2,3-methyleneoxyphenyl, 3,4-methyleneoxyphenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, m-chlorophenyl, p-chlorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl, o-cyanophenyl, m-cyanophenyl, p-cyanophenyl, naphth-1-yl, naphth-2-yl, biphenyl, pyridyl, thiophene, etc.

[0014] The alkoxy group refers to a straight-chain or branched alkoxy group having 1 to 6 carbon atoms, such as: methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, sec-butoxy, pentoxy, isopentoxy, sec-pentoxy, neopentoxy, hexoxy, isohexoxy, particularly preferred are straight-chain or branched alkoxy groups having 1 to 3 carbon atoms, and most preferably methoxy and ethoxy.

[0015] The alkynyl group refers to an alkynyl group having 3 to 9 carbon atoms, such as: prop-1-alkynyl, prop-2-alkynyl, but-1-alkynyl, but-2-alkynyl, but-2-alkynyl, pent-1-alkynyl, pent-2-alkynyl, pent-3-alkynyl, pent-4-alkynyl, hex-1-alkynyl, hex-2-alkynyl, hex-3-alkynyl, hex-4-alkynyl, hex-5-alkynyl, hep-1-alkynyl, hep-2-alkynyl, hep-3-alkynyl, hep-4-alkynyl, hep-5-alkynyl, hep-6-alkynyl Oct-1-ynyl, Oct-2-ynyl, Oct-3-ynyl, Oct-4-ynyl, Oct-5-ynyl, Oct-6-ynyl, Oct-7-ynyl, Non-1-ynyl, Non-2-ynyl, Non-3-ynyl, Non-4-ynyl, Non-5-ynyl, Non-6-ynyl, Non-7-ynyl, Non-8-ynyl, Phenylacetyl, 3-phenylprop-1-ynyl, 3-phenylprop-2-ynyl, o-m-p-methylphenylacetyl, with particular preference for phenylacetyl and o-m-p-methylphenylacetyl.

[0016] The ester group refers to an ester group having 2 to 6 carbon atoms, such as: methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, sec-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl, sec-pentoxycarbonyl, neopentoxycarbonyl, hexoxycarbonyl, isohexoxycarbonyl, and isohexoxycarbonyl. Straight-chain or branched alkoxycarbonyl groups having 2 to 3 carbon atoms are particularly preferred, and methoxycarbonyl and ethoxycarbonyl are most preferred.

[0017] The 2-alkylthiobenzo[b]thiophene sulfone compounds prepared include, for example, the following twenty-six compounds 1a to 1z:

[0018] (R 1 The position of a substituent refers to its location within the product structure; unless otherwise specified, R... 4 =Me)

[0019] 1a: R 1 =6-Me,R 2 =Ph,R 3 =Me;

[0020] 1b: R 1 =6-Me,R 2 =4-FC6H4,R 3 =Me;

[0021] 1c:R 1 =6-Me,R 2 =4-ClC6H4,R 3 =Me;

[0022] 1d:R 1 =6-Me,R 2 =4-BrC6H4,R 3 =Me;

[0023] 1e:R 1 =6-Me,R 2 =4-IC6H4,R 3 =Me;

[0024] 1f:R 1 =6-Me,R 2 =2-ClC6H4,R 3 =Me;

[0025] 1g:R 1 =6-Me,R 2 =3-ClC6H4,R 3 =Me;

[0026] 1h: R 1 =6-Me,R 2 =4-MeC6H4,R 3 =Me;

[0027] 1i:R 1 =6-Me,R 2 =4-cyclohexylC6H4,R 3 =Me;

[0028] 1j:R 1 =6-Me,R2 =4-PhC6H4,R 3 =Me;

[0029] 1k:R 1 =6-Me,R 2 =(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthalen-2-yl),R 3 =Me;

[0030] 1l:R 1 =6-Me,R 2 =4-MeO2CC6H4,R 3 =Me;

[0031] 1m:R 1 =6-MeO,R 2 =4-MeO2CC6H4,R 3 =Me;

[0032] 1n:R 1 =6-Me,R 2 =2-Naph,R 3 =Me;

[0033] 1o:R 1 =6-Me,R 2 =4-(2,6-dichloropyridin-3-yl)C6H4,R 3 =Me;

[0034] 1p:R 1 =6-Me,R 2 =thiophen-3-yl,R 3 =Me;

[0035] 1q:R 1 =6-F,R 2 =Ph,R 3 =Me;

[0036] 1r:R 1 =6-CMe3,R 2 =Ph,R 3 =Me;

[0037] 1s:R 1 =6-CHMe2,R 2 =Ph,R 3 =Me;

[0038] 1t:R 1 =6-MeO,R 2 =Ph,R3 =Me;

[0039] 1u:R 1 =6-Ph,R 2 =Ph,R 3 =Me;

[0040] 1v:R 1 =6-PhC≡C,R 2 =Ph,R 3 =Me;

[0041] 1w:R 1 =benzo[g],R 2 =Ph,R 3 =Me;

[0042] 1x:R 1 =6-Me,R 2 =Ph,R 3 =Et; (R in Equation 2) 4 =Et)

[0043] 1y:R 1 =6-Me,R 2 =Ph,R 3 =Ph;

[0044] 1z:R 1 =6-Me,R 2 =Ph,R 3 =CD3;

[0045] The above-mentioned preparation method usually involves preparing 2-alkylthiobenzo[b]thiophene sulfone compounds by cyclization of acylsulfonylmethylthioylide compounds (Formula 1) in the presence of a base induced by acid anhydride or acyl halide.

[0046] In the above preparation method, the acylsulfonylmethylthioylide compound raw material can be prepared directly according to the literature method.

[0047] The above preparation method uses sulfonic anhydride or carboxylic anhydride, such as trifluoromethanesulfonic anhydride, methanesulfonic anhydride, pentafluoroethanesulfonic anhydride, ethanesulfonic anhydride, isosulfonic anhydride, benzenesulfonic anhydride, p-toluenesulfonic anhydride, p-chlorobenzenesulfonic anhydride, p-fluorobenzenesulfonic anhydride, p-bromobenzenesulfonic anhydride, p-cyanobenzenesulfonic anhydride, p-nitrobenzenesulfonic anhydride, p-methoxycarbonylbenzenesulfonic anhydride, trifluoroacetic anhydride, trichloroacetic anhydride, acetic anhydride, propionic anhydride, benzoic anhydride, phthalic anhydride, etc.

[0048] The acyl halide used in the above preparation method is a sulfonyl halide or a carboxylic acid acyl halide, such as trifluoromethanesulfonyl chloride, methanesulfonyl chloride, pentafluoroethanesulfonyl chloride, ethanesulfonyl chloride, isosulfonyl chloride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-chlorobenzenesulfonyl chloride, p-fluorobenzenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-cyanobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride, p-methoxycarbonylbenzenesulfonyl chloride, trifluoroacetyl chloride, trichloroacetyl chloride, acetyl chloride, propionyl chloride, benzoyl chloride, etc.

[0049] The above preparation method uses organic bases such as tertiary amines or pyridine and their derivatives, or inorganic bases such as organic bases such as trimethylamine, triethylamine, tripropylamine, tributylamine, tripentylamine, trihexylamine, pyridine, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, quinoline, isoquinoline, 2-fluoroquinoline, 2-chloroquinoline, 2-bromoquinoline, 1-fluoroisoquinoline, 1-chloroisoquinoline, 1-bromoisoquinoline, 3-fluoroisoquinoline, 3-chloroisoquinoline, 3-bromoisoquinoline, DBU, DBN, DABCO, etc.; and inorganic bases such as potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium isopropoxide, sodium isopropoxide, lithium isopropoxide, sodium hydride, potassium hydride, lithium hydride, potassium carbonate, sodium carbonate, potassium acetate, sodium acetate, etc.

[0050] The solvents commonly used in the above preparation methods are dichloromethane, chloroform, 1,2-dichloroethane, tetrachloroethylene, dimethyl sulfoxide, cyclobutane sulfoxide, dimethyl sulfone, cyclobutane sulfone, acetonitrile, propionitrile, butyronitrile, valerate, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, benzene, toluene, xylene, trimethylbenzene, ethylbenzene, propylbenzene, isopropylbenzene, chlorobenzene, dichlorobenzene, trichlorobenzene, or mixtures thereof.

[0051] The above preparation method uses a reaction temperature of 0-150℃. The reaction can be carried out using an ice-water bath, a low-temperature bath, an acetone dry ice bath, or acetone plus liquid nitrogen for cooling. Heating can be carried out using traditional steam heating, electric heating, or microwave heating.

[0052] The above preparation method uses reaction conditions that can be carried out under nitrogen or argon protection in an anhydrous solvent.

[0053] Advantages and positive effects of the present invention:

[0054] The 2-alkylthiobenzo[b]thiophene sulfone compounds prepared in this invention are a very important class of organic intermediates with wide applications in pharmaceutical, pesticide chemistry and synthetic chemistry. They also exhibit various biological activities such as antiviral, antibacterial and enzyme inhibitory effects, and can be used as luminescent materials.

[0055] The preparation method provided by this invention uses readily available acylsulfonylmethylthioylide compounds as raw materials, which can be prepared using known methods. This method is simple to operate, has a short synthetic route, and can be used to synthesize 2-alkylthiobenzo[b]thiophene sulfone compounds with diverse structures. It is suitable for large-scale preparation and is of great significance for the preparation and application of such compounds. Detailed Implementation

[0056] The present invention will be further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein.

[0057] Example 1

[0058] 6-Methyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1a

[0059] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), trifluoromethanesulfonic anhydride (50.5 μL, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Eluents of petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) were used to give pale yellow crystals, 45 mg, 74% yield. Mp 148-150 °C; R f =0.53(PE / EA5:1,v / v). 1 H NMR (400MHz, CDCl3) δ7.60(s,1H),7.58-7.46(m,3H),7.46-7.38(m,2H),7.29(d,J=7.8Hz,1H),7.11(d,J=7.8Hz,1H),2.57(s,3H),2.44(s,3H). 13 CNMR (101MHz, CDCl3) δ141.1,140.7,137.1,134.1,134.0,130.7,130.3,129.8,129.0,128.9,123.4,122.4,21.5,15.8.

[0060] Example 2

[0061] 3-(4-fluorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1b

[0062] Following the method described in Example 1, 3-(4-fluorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 4-fluorobenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material; it was a pale yellow crystal, 40 mg, 63% yield. MP 130-131℃; R f =0.51(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.60 (dq, J=1.2, 0.4Hz, 1H), 7.42 (dd, J=8.8, 5.2Hz, 1H), 7.30 (ddd, J =7.8,1.6,0.8Hz,1H),7.26-7.19(m,2H),7.08(d,J=7.8Hz,2H),2.58(s,3H),2.44(s,3H). 13 C NMR (101MHz, CDCl3) δ163.4 (d, J = 250.6Hz), 140.8, 139.9, 137.1, 134.3, 134.2, 131.1 ( d,J=8.5Hz),130.1,126.6(d,J=3.0Hz),123.2,122.5,116.2(d,J=21.9Hz),21.5,15.7. 19 F NMR (376MHz, CDCl3) δ-110.2.

[0063] Example 3

[0064] 3-(4-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1c

[0065] Following the method described in Example 1, 3-(4-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 4-chlorobenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material; it was a pale yellow crystal, 39 mg, 58% yield. MP 139-140℃; R f =0.60(PE / EA5:1,v / v). 1 H NMR (400MHz, CDCl3) δ7.60(dq,J=1.7,0.8Hz,1H),7.51(d,J=8.5Hz,2H),7.37(d,J=8.5Hz ,2H),7.30(ddd,J=7.8,1.7,0.8Hz,1H),7.07(d,J=7.8Hz,1H),2.59(s,3H),2.44(s,3H). 13C NMR (101MHz, CDCl3) δ140.8,139.6,137.0,135.9,134.6,134.2,130.4,129.9,129.3,129.1,123.1,122.5,21.5,15.6.

[0066] Example 4

[0067] 3-(4-bromophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1d

[0068] Following the method described in Example 1, 3-(4-bromophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 4-bromobenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material, as a yellow oil, 45 mg, 59% yield. MP 144-145℃; R f =0.51(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.67(d,J=8.0Hz,2H),7.60(s,1H),7.30(d,J=8.0Hz,3H),7.07(d,J=7.9Hz,1H),2.59(s,3H),2.44(s,3H). 13 C NMR (101MHz, CDCl3) δ140.9,139.6,137.0,134.6,134.2,132.3,130.6,129.9,129.6,124.2,123.1,122.6,21.5,15.6.

[0069] Example 5

[0070] 3-(4-iodophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1e

[0071] Following the method described in Example 1, 3-(4-iodophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 4-iodobenzoyl-p-toluenesulfonyl methyl dimethyl sulfonate as a starting material; it was a pale yellow crystal, 40 mg, 47% yield. MP 150-151℃; R f =0.28(PE / EA1:1,v / v). 1 H NMR (400MHz, CDCl3) δ7.89(d,J=8.4Hz,2H),7.62(s,1H),7.32(d,J=7.8Hz,1H),7.18(d,J=8.4Hz,2H),7.09(d,J=7.9Hz,1H),2.61(s,3H),2.46(s,3H). 13C NMR (101MHz, CDCl3) δ140.8,139.7,138.2,137.0,134.5,134.2,130.7,130.1,129.8,123.1,122.5,96.0,21.5,15.6.

[0072] Example 6

[0073] 3-(2-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1f

[0074] Following the method described in Example 1, 3-(2-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 2-chlorobenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. It was a colorless crystal, 30 mg, 74% yield. MP 129-130℃; R f =0.40(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.59(s,1H),7.55(dd,J=7.8,1.5Hz,1H),7.45(ddd,J=9.6,7.6,1.5Hz,1H),7. 41(ddd,J=9.2,7.6,1.2Hz,1H),7.30-7.25(m,2H),6.81(d,J=7.8Hz,1H),2.57(s,3H),2.43(s,3H). 13 C NMR (101MHz, CDCl3) δ140.7,139.2,136.7,136.5,134.2,133.3,131.0,130.6,130.3,130.1,129.8,127.3,123.2,122.3,21.5,15.4.

[0075] Example 7

[0076] 1g of 3-(3-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone

[0077] Following the method described in Example 1, 3-(3-chlorophenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained from 3-chlorobenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. The precipitate was a pale yellow crystal, 50 mg, 45% yield. MP 115-116℃; R f =0.46(PE / EA 5:1, v / v). 1H NMR (400MHz, CDCl3) δ7.61 (s, 1H), 7.51-7.47 (m, 2H), 7.43-7.41 (m, 1H), 7.35-7.28 (m, 2H), 7.08 (d, J = 7.8Hz, 1H), 2.61 (s, 3H), 2.45 (s, 3H). 13 C NMR (101MHz, CDCl3) δ140.9,139.0,137.0,135.1,135.0,134.3,132.5,130.3,130.0,129.0,128.7,127.3,123.1,122.6,21.5,15.5.

[0078] Example 8

[0079] 6-Methyl-3-(4-methylphenyl)-2-methylthiobenzo[b]thiophene sulfone 1h

[0080] Following the method described in Example 1, 6-methyl-3-(4-methylphenyl)-2-methylthiobenzo[b]thiophene sulfone was obtained from 4-methylbenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. It was a colorless crystal, 46 mg, 73% yield. MPa: 145-146 °C. f =0.38(PE / EA10:1,v / v). 1 H NMR (400MHz, CDCl3) δ7.59 (s, 1H), 7.35-7.30 (m, 4H), 7.32-7.25 (m, 1H), 7.13 (d, J = 7.8Hz, 1H), 2.56 (s, 3H), 2.44 (s, 3H), 2.43 (s, 3H). 13 C NMR (101MHz, CDCl3) δ141.4,140.6,140.1,137.2,134.1,133.4,130.4,129.6,128.9,127.6,123.5,122.3,21.6,21.5,15.9.

[0081] Example 9

[0082] 3-(4-cyclohexylphenyl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1i

[0083] Following the method described in Example 1, 3-(4-cyclohexylbenzoyl-p-toluenesulfonylmethyldimethylsulfonate) was obtained from 4-cyclohexylbenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. The resulting product was a pale yellow crystal, 32 mg, 42% yield. MP 179-180℃; R f =0.36(PE / EA 10:1, v / v).1 H NMR (400MHz, CDCl3) δ7.59(s,1H),7.35(s,4H),7.28(d,J=7.9Hz,1H),7.17(d,J=7.9Hz,1H),2.61-2.54(m, 1H),2.57(s,3H),2.44(s,3H),2.00-1.84(m,4H),1.84-1.70(m,1H),1.50-1.38(m,4H),1.30-1.25(m,1H). 13 CNMR (101MHz, CDCl3) δ150.0,141.4,140.6,137.2,134.0,133.3,130.5,129.0,127.9,127.3,123.6,122.3,44.6,34.4,27.0,26.2,21.5,16.0.

[0084] Example 10

[0085] 6-Methyl-2-methylthio-3-(4-phenylphenyl)benzo[b]thiophene sulfone 1j

[0086] Following the method described in Example 1, 6-methyl-2-methylthio-3-(4-phenylphenyl)benzo[b]thiophene sulfone was obtained from 4-phenylbenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. It was a colorless crystal, 40 mg, 53% yield. MP 191-192 °C; R f =0.29(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.75 (d, J = 8.3Hz, 2H), 7.69-7.62 (m, 2H), 7.62 (s, 1H), 7.54-7.44 (m, 4H), 7.40 (t,J=7.4Hz,1H),7.31(ddd,J=7.8,1.7,0.9Hz,1H),7.19(d,J=7.9Hz,1H),2.60(s,3H),2.45(s,3H). 13 C NMR (101MHz, CDCl3) δ142.7,140.8,140.7,140.2,137.1,134.1,133.9,130 .3,129.52,129.48,129.1,128.0,127.6,127.3,123.5,122.4,21.5,15.9.

[0087] Example 11

[0088] 3-(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthyl-2-yl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1k

[0089] Following the method described in Example 1, using (3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthyl-2-yl)formyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material, 3-(3,5,5,6,8,8-hexamethyl-5,6,7,8-tetrahydronaphthyl-2-yl)-6-methyl-2-methylthiobenzo[b]thiophene sulfone was obtained as colorless crystals, 42 mg, 49% yield. Dr = 1:1, MP 181-183℃; R f =0.50(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.59-7.58(m,1H),7.27-7.26(m,1H),7.25-7.23(m,1H),7.05(s,0.5H),7.05(s,0.5H),6.86(d ,J=7.8Hz,0.5H),6.83(d,J=7.8Hz,0.5H),2.54(s,1.5H),2.53(s,1.5H),2.43(s,3H),2.16(s,1.5H),2.15(s,1.5H), 1.95-1.84(m,1H),1.66(t,J=13.2Hz,1H,)1.40(dd,J=13.2,3.2Hz,0.5H),1.38(dd,J=13.2,3.2Hz,0.5H),1.37(s,1. 5H),1.36(s,1.5H),1.27(s,1.5H),1.25(s,1.5H),1.24(s,3H),1.11(s,1.5H),1.10(s,1.5H),1.01(d,J=6.8Hz,3H), 13 C NMR (101MHz, CDCl3) δ147.5,142.85,142.79,142.0,141.9,140.4,137.04,137.00 ,134.6,134.5,134.17,134.15,132.8,132.7,131.0,130.9,129.2,129.1,127.34, 127.33,127.2,127.0,123.6,122.1,43.7,43.6,37.9,34.7,34.6,34.28,34.26,32.55,32.50,32.2,32.1,28.8,28.6,25.2,25.1,21.5,19.7,19.6,17.0,15.5,15.4.

[0090] Example 12

[0091] 1l of methyl 4-(6-methyl-2-methylthio-1,1-dioxanebenzo[b]thiophene-3-yl)benzoate

[0092] Following the method described in Example 1, methyl 4-(6-methyl-2-methylthio-1,1-dioxane-benzo[b]thiophene-3-yl)benzoate was obtained from 4-methoxycarbonylbenzoyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. The methyl benzoate was a light yellow crystal, 17 mg, 24% yield. MPa: 162-164 °C; R f =0.20(PE / EA 10:1, v / v). 1 H NMR(400MHz, CDCl3)δ8.20(d,J=8.5Hz,2H),7.64-7.60(m,1H),7.51(d,J=8.4Hz,2H),7.30 (ddd,J=7.8,1.7,0.8Hz,1H),7.06(d,J=7.9Hz,1H),3.97(s,3H),2.60(s,3H),2.45(s,3H). 13 C NMR (101MHz, CDCl3) δ166.5,140.9,139.5,137.0,135.3,135.2,134.3,131.3,130.2,129.8,129.1,123.1,122.6,52.6,21.5,15.5.

[0093] Example 13

[0094] 4-(6-methoxy-2-methylthio-1,1-dioxanebenzo[b]thiophene-3-yl)methyl benzoate 1m

[0095] Following the method described in Example 1, methyl 4-(6-methoxy-2-methylthio-1,1-dioxane-benzo[b]thiophene-3-yl)benzoate was obtained from 4-methoxycarbonylbenzoyl-p-methoxybenzenesulfonylmethyldimethylsulfonate as a starting material. The methyl benzoate was a light yellow crystal, 40 mg, 53% yield. MP 158-160℃; R f =0.30(PE / EA5:1,v / v). 1 H NMR (400MHz, CDCl3) δ8.20(d,J=8.5Hz,2H),7.52(d,J=8.4Hz,2H),7.35(d,J=2.4Hz,1H), 7.09(d,J=8.5Hz,1H),6.99(dd,J=8.5,2.4Hz,1H),3.97(s,3H),3.90(s,3H),2.56(s,3H).13 C NMR (101MHz, CDCl3) δ166.4,161.7,141.0,138.6,135.3,133.7,131.4,130.1,129.1,124.7,124.6,119.2,107.9,56.2,52.5,16.2.

[0096] Example 14

[0097] 6-Methyl-2-methylthio-3-(naphth-2-yl)benzo[b]thiophene sulfone 1n

[0098] Following the method described in Example 1, 6-methyl-2-methylthio-3-(naphthyl-2-yl)benzo[b]thiophene sulfone was obtained from (naphthyl-2-yl)formyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material. The precipitate was a pale yellow crystal, 30 mg, 43% yield. MPa: 143-144 °C; R f =0.45(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.99 (d, J = 8.5Hz, 1H), 7.95-7.85 (m, 3H), 7.63 (s, 1H), 7.61-7.54 (m, 2H), 7.52 (dd ,J=8.4,1.7Hz,1H),7.29(ddd,J=7.8,1.6,0.9Hz,1H),7.15(d,J=7.8Hz,1H),2.58(s,3H),2.45(s,3H). 13 C NMR (101MHz, CDCl3) δ141.0,140.7,137.2,134.3,134.2,133.7,133.1,130.4,12 9.0,128.7,128.5,128.1,128.0,127.5,127.0,125.8,123.5,122.4,21.5,15.8.

[0099] Example 15

[0100] 3-(2,6-Dichloropyridin-3-yl)phenyl-6-methyl-2-methylthiobenzo[b]thiophene sulfone 1o

[0101] Following the method described in Example 1, 3-(2,6-dichloropyridin-3-yl)benzoyl-p-toluenesulfonylmethyldimethylsulfonate was obtained from 4-(2,6-dichloropyridin-3-yl)phenyl-6-methyl-2-methylthiobenzo[b]thiophene sulfone, pale yellow crystals, 46 mg, 51% yield. MP 185-186℃; R f =0.48(PE / EA 3:1, v / v). 1H NMR (400MHz, CDCl3) δ7.73(d,J=7.9Hz,1H),7.61(s,1H),7.61(d,J=8.2Hz,2H),7.54(d,J=8.2Hz, 2H),7.41(d,J=7.9Hz,1H),7.33(d,J=7.9Hz,1H),7.18(d,J=7.9Hz,1H),2.63(s,3H),2.46(s,3H). 13 C NMR (101MHz, CDCl3) δ149.6,148.6,141.9,140.8,139.8,137.6,137.0,134.8 ,134.2,131.1,130.1,130.0,129.8,129.2,123.4,123.3,122.5,21.5,15.6.

[0102] Example 16

[0103] 6-Methyl-2-methylthio-3-(thiophen-3-yl)benzo[b]thiophene sulfone 1p

[0104] Following the method described in Example 1, 6-methyl-2-methylthio-3-(thien-3-yl)benzo[b]thiophene sulfone was obtained from (thien-3-yl)formyl-p-toluenesulfonylmethyldimethylsulfonate as a starting material; colorless crystals, 32 mg, 52% yield. MP 128-129℃; R f =0.40(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.63-7.55(m,2H),7.51(dd,J=5.0,2.9Hz,1H),7.36-7.27(m,3H),2.60(s,3H),2.44(s,3H). 13 C NMR (101MHz, CDCl3) δ140.6,137.1,135.9,134.2,133.5,130.7,130.1,127.8,127.6,126.6,123.3,122.4,21.5,15.8.

[0105] Example 17

[0106] 6-Fluoro-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1q

[0107] Following the method described in Example 1, 6-fluoro-2-methylthio-3-phenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-fluorobenzenesulfonyl methyl dimethyl sulfonate as a starting material; it was a pale yellow crystal, 14 mg, 23% yield. MP 144-146℃; R f=0.42(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.60-7.45(m,4H),7.45-7.37(m,2H),7.24-7.15(m,2H),2.58(s,1H). 13 C NMR (101MHz, CDCl3) δ163.6 (d, J = 255.9Hz), 140.2, 138.8 (d, J = 7.6Hz), 135.28, 135.27, 130. 2,130.1,129.1,128.9,125.2(d,J=8.0Hz),120.4(d,J=22.5Hz),110.4(d,J=26.6Hz),15.8. 19 F NMR (376MHz, CDCl3) δ-108.6.

[0108] Example 18

[0109] 6-tert-butyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1r

[0110] Following the method described in Example 1, 6-tert-butyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-tert-butylbenzenesulfonylmethyldimethylsulfonate as a starting material. The precipitate was a pale yellow crystal, 40 mg, 58% yield. MPa: 176-178 °C; R f =0.48(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.83(d,J=1.8Hz,1H),7.61-7.49(m,4H),7.46-7.34(m,2H),7.16(d,J=8.1Hz,1H),2.57(s,3H),1.35(s,9H). 13 C NMR (101MHz, CDCl3) δ154.1,141.1,137.0,134.3,130.66,130.63,130.2,129.8,129.0,128.9,123.3,118.9,35.5,31.2,15.9.

[0111] Example 19

[0112] 6-Isopropyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1s

[0113] Following the method described in Example 1, 6-isopropyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-isopropylbenzenesulfonylmethyldimethylsulfonate as a starting material. The precipitate was a pale yellow crystal, 50 mg, 76% yield. MPa 10³-10⁴ °C. f =0.50(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.67(d,J=1.6Hz,1H),7.57-7.46(m,3H),7.44-7.39(m,2H),7.34(dd,J=7.9 ,1.7Hz,1H),7.14(d,J=8.0Hz,1H),2.99(hept,J=6.9Hz,1H),2.57(s,3H),1.28(d,J=6.9Hz,6H). 13 C NMR (101MHz, CDCl3) δ 151.6, 141.2, 137.1, 134.1, 131.8, 130.63, 130.55, 129.8, 128.91, 128.88, 123.6, 119.8, 34.2, 23.7, 15.8. Example 20

[0114] 6-Methoxy-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1t

[0115] Following the method described in Example 1, 6-methoxy-2-methylthio-3-phenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-methoxybenzenesulfonylmethyldimethylsulfonate as a starting material; it was a pale yellow crystal, 46 mg, 72% yield. MPa 106-108℃; R f =0.29(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.57-7.47(m,3H),7.44-7.38(m,2H),7.34(d,J=2.4Hz,1H ),7.15(d,J=8.5Hz,1H),6.98(dd,J=8.5,2.5Hz,1H),3.89(s,3H),2.53(s,3H). 13 C NMR (101MHz, CDCl3) δ161.5,142.5,138.7,132.6,130.7,129.9,129.0,128.9,125.1,125.0,119.1,107.7,56.2,16.5.

[0116] Example 21

[0117] 2-Methylthio-3,6-diphenylbenzo[b]thiophene sulfone 1u

[0118] Following the method described in Example 1, 2-methylthio-3,6-diphenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-phenylbenzenesulfonylmethyldimethylsulfonate as a starting material. The crystalline powder was pale yellow, 40 mg, 55% yield. MP 178-178℃; R f =0.55(PE / EA 5:1, v / v). 1 H NMR (400MHz, CDCl3) δ8.01 (d, J = 1.7Hz, 1H), 7.70 (dd, J = 8.0, 1.7Hz, 1H), 7.63-7.51 (m, 5H), 7.50-7.40 (m, 5H), 7.29 (d, J = 7.9Hz, 1H), 2.61 (s, 3H). 13 C NMR (101MHz, CDCl3) δ143.1,140.3,138.8,137.8,135.1,132.1,131.6,130.6,129.9,129.3,129.03,129.00,128.7,127.1,123.9,120.4,15.6.

[0119] Example 22

[0120] 2-Methylthio-3-phenyl-6-phenylethynyl-benzo[b]thiophene sulfone 1v

[0121] Following the method described in Example 1, 2-methylthio-3-phenyl-6-phenylethynyl-benzo[b]thiophene sulfone was obtained from benzoyl-p-phenylethynylbenzenesulfonylmethyldimethylsulfonate as a starting material. The precipitate was a pale yellow crystal, 35 mg, 45% yield. MP 165-166℃; R f =0.31(PE / EA 10:1, v / v). 1 H NMR (400MHz, CDCl3) δ7.91 (d, J=1.5Hz, 1H), 7.61 (dd, J=8.0, 1.5Hz, 1H), 7.59-7.4 9(m,5H),7.47-7.40(m,2H),7.40-7.35(m,3H),7.19(d,J=7.9Hz,1H),2.62(s,3H). 13 C NMR (101MHz, CDCl3) δ 139.4, 137.2, 136.5, 136.2, 132.0, 131.9, 130.4, 130.0, 129.2, 129.1, 129.0, 128.6, 125.1, 124.6, 123.2, 122.4, 93.6, 87.6, 15.3. Example 23

[0122] 2-Methylthio-3-phenylnaphtho[1,2-b]thiophene sulfone 1w

[0123] Following the method described in Example 1, 2-methylthio-3-phenylnaphtho[1,2-b]thiophene sulfone was obtained from benzoyl(naphthalene-2-yl)sulfonylmethyldimethylsulfonate as a starting material; yellow crystals, 45 mg, 67% yield. MP 144-146℃; R f =0.50(PE / EA 5:1, v / v). 1 H NMR(400MHz, CDCl3)δ8.37(dd,J=8.4,1.0Hz,1H),8.00-7.94(m,1H),7.89(d,J=8.2Hz,1H),7.71(dd d,J=8.3,6.9,1.2Hz,1H),7.62-7.51(m,4H),7.49-7.44(m,2H),7.32(d,J=8.5Hz,1H),2.65(s,3H). 13 C NMR (101MHz, CDCl3) δ140.3,135.8,134.1,133.8,131.5,131.2,130.7,129.9,129.6,129.1,129.0,128.9,127.7,126.2,123.4,120.0,15.6.

[0124] Example 24

[0125] 2-Ethylthio-6-methyl-3-phenylbenzo[b]thiophene sulfone 1x

[0126] Following the method described in Example 1, 2-ethylthio-6-methyl-3-phenylbenzo[b]thiophene sulfone was obtained from benzoyl-p-toluenesulfonyl methyl diethyl sulfonate as a starting material; a pale yellow oil, 44 mg, 70% yield. f =0.35(PE / EA 10:1, v / v). 1 H NMR(400MHz, CDCl3)δ7.62(s,1H),7.56-7.47(m,3H),7.44-7.38(m,2H),7.29(ddd,J=7.8,1.7 ,0.8Hz,1H),7.12(d,J=7.8Hz,1H),3.07(q,J=7.4Hz,2H),2.44(s,3H),1.27(t,J=7.4Hz,3H). 13C NMR (101MHz, CDCl3) δ143.1,140.9,137.2,134.1,133.2,130.7,130.4,129.8,129.0,128.9,123.7,122.5,27.4,21.5,15.1.

[0127] Example 25

[0128] 6-Methyl-3-phenyl-2-phenylthiobenzo[b]thiophene sulfone 1y

[0129] Following the method described in Example 1, 6-methyl-3-phenyl-2-phenylthiobenzo[b]thiophene sulfone was obtained from benzoyl-p-toluenesulfonylmethylmethylphenylsulfonium salt as a starting material; yellow crystals, 42 mg, 58% yield. MP 162-163℃; R f =0.12(PE / EA 10:1, v / v). 1 H NMR(400MHz, CDCl3)δ7.62(s,1H),7.50-7.44(m,3H),7.45-7.40(m,2H),7.39-7.3 5(m,2H),7.33-7.28(m,1H),7.26-7.18(m,3H),7.17(d,J=7.8Hz,1H),2.44(s,3H). 13 C NMR (101MHz, CDCl3) δ147.6,142.0,137.2,134.0,131.9,131.0,130.3,130.1,129.9,129.2,128.9,128.8,128.0,124.4,122.7,21.6.

[0130] Example 26

[0131] 6-Methyl-2-trideuterated methylthio-3-phenylbenzo[b]thiophene sulfone 1z

[0132] Benzoyl-p-toluenesulfonylmethyl di(trideuterated methyl)sulfonium salt (68 mg, 0.20 mmol), trifluoromethanesulfonic anhydride (50.5 μL, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Eluent was obtained from petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) to give pale yellow crystals, 40 mg, 66% yield. Mp 151-153 °C; R f =0.58(PE / EA 5:1, v / v). 1H NMR (400MHz, CDCl3) δ7.60 (s, 1H), 7.58-7.45 (m, 3H), 7.46-7.37 (m, 2H), 7.29 (d, J = 7.8, 1H), 7.11 (d, J = 7.9Hz, 1H), 2.44 (s, 3H). 13 C NMR (101MHz, CDCl3) δ141.0,140.6,137.1,134.1,133.9,130.7,130.3,129.8,129.0,128.9,123.4,122.4,21.5.

[0133] Example 27

[0134] 6-Methyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1a

[0135] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), trifluoromethanesulfonic anhydride (50.5 μL, 0.3 mmol), and triethylamine (33 mg, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Elution with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) yielded pale yellow crystals, 13 mg, 22% yield.

[0136] Example 28

[0137] 6-Methyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1a

[0138] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), trifluoromethanesulfonic anhydride (50.5 μL, 0.3 mmol), and DBU (49 mg, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Elution with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) yielded pale yellow crystals, 11 mg, 18% yield.

[0139] Example 29

[0140] 6-Methyl-2-methylthio-3-phenylbenzo[b]thiophene sulfone 1a

[0141] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), methanesulfonic anhydride (52 mg, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Elution with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) yielded pale yellow crystals, 11 mg, 18% yield.

[0142] Example 30

[0143] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), trifluoroacetic anhydride (63 mg, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Elution with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) yielded pale yellow crystals, 12 mg, 20% yield.

[0144] Example 31

[0145] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), trifluoromethanesulfonyl chloride (50.5 mg, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. Elution with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) yielded pale yellow crystals, 26 mg, 48% yield.

[0146] Example 32

[0147] Benzoyl-p-toluenesulfonyl methyl dimethyl sulfonium salt (66.8 mg, 0.20 mmol), methanesulfonyl chloride (34 mg, 0.3 mmol), and 2-chloropyridine (30 μL, 0.32 mmol) were added to a dry reaction tube under nitrogen atmosphere. 3 mL of dichloroethane was added, and the mixture was stirred at 90 °C for 8 hours. After cooling, the solvent was evaporated, and the residue was separated by silica gel column chromatography. The residue was eluted with petroleum ether, ethyl acetate, and dichloromethane (25:1:1, v / v) to give pale yellow crystals, 13 mg, 22% yield.

Claims

1. A 2-hydrothiobenzo[a] as shown in Formula 2 b The preparation method of thiophene sulfone compounds involves reacting an acylsulfonylmethylthioylide compound of formula 1 with an acid anhydride or acyl halide in the presence of a base to obtain 2-alkylthiobenzo[] as shown in formula 2. b Thiophene sulfone compounds; in: R 1 Represents hydrogen, halogen, alkyl group having 1 to 6 carbon atoms, cycloalkyl group having 3 to 6 carbon atoms, alkynyl group having 3 to 9 carbon atoms, alkoxy group having 1 to 6 carbon atoms, ester group having 2 to 6 carbon atoms, aryl group having 6 to 12 carbon atoms, wherein the aryl group may contain alkyl group having 1 to 6 carbon atoms, fluorine, chlorine, bromine, cyano, nitro, or dimethylamino as substituents; R 2 and R 3 This indicates an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, or an aryl group having 6 to 12 carbon atoms. The aryl group may contain alkyl groups having 1 to 6 carbon atoms, fluorine, chlorine, bromine, cyano, nitro, or dimethylamino groups as substituents; R 4 Indicates alkyl groups having 1 to 6 carbon atoms, or cycloalkyl groups having 3 to 6 carbon atoms; R 1 R 2 R 3 and R 4 They can be the same or different.

2. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The anhydride used is a sulfonic acid anhydride or a carboxylic acid anhydride, specifically selected from trifluoromethanesulfonic anhydride, methanesulfonic anhydride, pentafluoroethanesulfonic anhydride, ethanesulfonic anhydride, isosulfonic anhydride, benzenesulfonic anhydride, p-toluenesulfonic anhydride, p-chlorobenzenesulfonic anhydride, p-fluorobenzenesulfonic anhydride, p-bromobenzenesulfonic anhydride, p-cyanobenzenesulfonic anhydride, p-nitrobenzenesulfonic anhydride, p-methoxycarbonylbenzenesulfonic anhydride, trifluoroacetic anhydride, trichloroacetic anhydride, acetic anhydride, propionic anhydride, benzoic anhydride, and phthalic anhydride.

3. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The acyl halide used is a sulfonyl halide or a carboxylic acid acyl halide, specifically selected from trifluoromethanesulfonyl chloride, methanesulfonyl chloride, pentafluoroethanesulfonyl chloride, ethanesulfonyl chloride, isosulfonyl chloride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-chlorobenzenesulfonyl chloride, p-fluorobenzenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-cyanobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride, p-methoxycarbonylbenzenesulfonyl chloride, trifluoroacetyl chloride, trichloroacetyl chloride, acetyl chloride, propionyl chloride, and benzoyl chloride.

4. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The base used is selected from trimethylamine, triethylamine, tripropylamine, tributylamine, tripentylamine, trihexylamine, pyridine, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, quinoline, isoquinoline, 2-fluoroquinoline, 2-chloroquinoline, 2-bromoquinoline, 1-fluoroisoquinoline, 1-chloroisoquinoline, 1-bromoisoquinoline, 3-fluoroisoquinoline, 3-chloroisoquinoline, 3-bromoisoquinoline, DBU, DBN, DABCO; inorganic bases such as potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium isopropoxide, sodium isopropoxide, lithium isopropoxide, sodium hydride, potassium hydride, lithium hydride, potassium carbonate, sodium carbonate, potassium acetate, sodium acetate; or mixtures thereof.

5. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The solvents used are dichloromethane, chloroform, 1,2-dichloroethane, tetrachloroethylene, dimethyl sulfoxide, cyclobutane sulfoxide, dimethyl sulfone, cyclobutane sulfone, acetonitrile, propionitrile, butyronitrile, valerate, tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, benzene, toluene, xylene, trimethylbenzene, ethylbenzene, propylbenzene, isopropylbenzene, chlorobenzene, dichlorobenzene, trichlorobenzene, or mixtures thereof.

6. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The reaction temperature used is 0–150 °C o C. The reaction can be cooled by an ice-water bath, a low-temperature bath, an acetone dry ice bath, or acetone plus liquid nitrogen. Heating can be carried out by traditional steam heating, electric heating, or microwave heating.

7. The 2-hydroxythiobenzo[] as described in claim 1 b The method for preparing thiophene sulfone compounds is characterized by... The reaction was carried out under nitrogen or argon protection in an anhydrous solvent.

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