CN110746393A - Synthesis method of 3-methylthio substituted benzofuran compound - Google Patents

Synthesis method of 3-methylthio substituted benzofuran compound Download PDF

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CN110746393A
CN110746393A CN201911050493.9A CN201911050493A CN110746393A CN 110746393 A CN110746393 A CN 110746393A CN 201911050493 A CN201911050493 A CN 201911050493A CN 110746393 A CN110746393 A CN 110746393A
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phenyl
ethynyl
anisole
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CN110746393B (en
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杜云飞
张蓓蓓
赵康
李孝贤
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Hebei Kainuo Zhongxing Technology Co ltd
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Tianjin University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

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Abstract

The invention discloses a synthesis method of a 3-methylthio substituted benzofuran compound, which comprises the following steps: dissolving a compound I and dimethyl sulfoxide in toluene, dropwise adding thionyl chloride, and reacting at room temperature to obtain a 3-methylthio-substituted benzofuran compound (II);
Figure DDA0002255212750000011
the compound I is 2- ((2-R)2) -ethynyl) anisole or 2- ((2-R)2) -ethynyl) phenol; the method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, no need of metal catalysis, short reaction time, high yield and the like.

Description

Synthesis method of 3-methylthio substituted benzofuran compound
Technical Field
The invention relates to a synthesis method of 3-methylthio substituted benzofuran derivatives.
Background
Benzofuran as an important benzo heteroaromatic ring compound widely exists in a plurality of natural products and medical intermediates1Having a wide range of pharmacological activities including anti-cancer activity2And anti-rheumatoid activity3Anti-viral pathogen Activity4And antifungal activity5And the activity of immunosuppression6And anti-platelet activity7AntiActivity of oxidation8And insecticidal activity9Anti-inflammatory activity10Anti-food activity11And cancer prevention activity12And the like. In view of their importance, several structural benzo [ b ] s have been developed]A method for preparing furan structure skeleton. It should be noted that, although most of the existing synthetic methods are effective and reliable, the existing synthetic methods still have the defects of metal catalysis, complex operation, low atom economy and the like, so that the existing synthetic methods cannot be widely applied to actual production. Therefore, the synthesis of benzo [ b ] via simple procedures using inexpensive and readily available reagents as starting materials has been studied and developed]The furan compound has important theoretical significance and application value.
See in particular the following references:
1.Dean,F M.The Total Synthesis of Natural Products；ApSimon,J.,Ed,Wiley:New York,1973,vol.1,pp 467-562.
2.Navarro,E.；Alonso,S.J.；Trujillo,J.；Jorge,E.；Perez,C.J.Nat.Prod.2001,64,134.
3.Ikeda,R.；Nagao,T.；Okabe,H.；Nakano.Y.；Matsunaga,H.；Katano,M.；Mori,M.Chem.Pharm.Bull.1998,46,871.
4.Leung.C.；Charlton,J.L.；Cow,C.Can.J.Chem.2000,78,553.
5.Carter,G.A.；Chamberlain,K.；Wain,R.L.Ann.Appl.Bio.1978,88,57.
6.Cho.J.Y.；Kim,A.R.；Yoo,E.S.；Baik,K.U.；Park,M.H.J.Pharm.Pharmacol.1999,51,1267.
7.Chen,C.C.；Hsin,W.C.；Ko,F.N.；Huang,Y.L.；Ou,J.C.；Teng,C.M.J.Nat.Prod.1996,59,1149.
8.Masuda,S.；Hasuda,H.；Tokoroyama,T.Chem.Pharm.Bull.1994,42,2500.
9.Findlay,J.A.；Buthelezi,S.；Li,G.；Seveck,M.；Miller,J.D.J.Nat.Prod.1997,60,1214.
10.Day,S.H.；Chiu,N.Y.；Tsao.L.T.；Wang,J.P.；Lin,C.N.J.Nat.Prod.2000,63,1560.
11.Ward,R.S.Nat.Prod.Rep.1995,12,183.
12.Oikannen,S.I.；Pajari,A.M.；Mutanen,M.CancerLett.2000,159,183.
disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for synthesizing a 3-methylthio substituted benzofuran derivative by simply realizing intramolecular cyclization and methionine tandem cyclization.
The technical scheme of the invention is summarized as follows:
the synthesis method of the 3-methylthio substituted benzofuran derivative comprises the following steps: dissolving a compound I and dimethyl sulfoxide in toluene, dropwise adding thionyl chloride, and reacting at room temperature to obtain a 3-methylthio-substituted benzofuran compound (II);
Figure BDA0002255212740000021
the compound I is 2- ((2-R)2) -ethynyl) anisole or 2- ((2-R)2) -ethynyl) phenol;
in the formula:
R1is a hydrogen atom, a methyl group or a chlorine atom;
R2is a hydrogen atom, a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-trifluoromethylphenyl group, a 3-methylphenyl group, a 3-methoxyphenyl group, a 3-chlorophenyl group, a 3-bromophenyl group, a 3-trifluoromethylphenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group, a 2-chlorophenyl group, a 2-bromophenyl group, a 2-thienyl group or a cyclopropyl group;
R3is a hydrogen atom or a methyl group.
Preferably, the molar ratio of compound I to thionyl chloride is 1: 2.
The synthesis method of the 3-methylthio substituted benzofuran derivative is characterized by comprising the following steps of: dissolving the compound I in deuterated dimethyl sulfoxide, dropwise adding thionyl chloride, and reacting at room temperature to obtain a 3-methylthio-substituted benzofuran compound (II');
Figure BDA0002255212740000022
the compound I is 2- ((2-R)2) -ethynyl) anisole or 2- ((2-R)2) -ethynyl) phenol;
in the formula:
R1is a hydrogen atom, a methyl group or a chlorine atom;
R2is a hydrogen atom, a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-trifluoromethylphenyl group, a 3-methylphenyl group, a 3-methoxyphenyl group, a 3-chlorophenyl group, a 3-bromophenyl group, a 3-trifluoromethylphenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group, a 2-chlorophenyl group, a 2-bromophenyl group, a 2-thienyl group or a cyclopropyl group;
R3is a hydrogen atom or a methyl group;
preferably, the molar ratio of compound I to thionyl chloride is 1: 2.
The invention has the advantages that:
the method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, no need of metal catalysis, short reaction time, high yield and the like.
Detailed Description
Thionyl chloride (SOCl)2) Analytically pure thionyl chloride purchased commercially.
Dimethyl sulfoxide (DMSO) is a commercially available absolute anhydrous dimethyl sulfoxide.
Deuterated dimethyl sulfoxide (DMSO-d)6) Commercially available deuterated dimethyl sulfoxide of 99.9% purity.
The present invention will be further illustrated by the following specific examples.
Example 1
Preparation of 2-phenyl-3-methylthiobenzofuran II-a
Figure BDA0002255212740000031
2- ((2-phenyl) -ethynyl) anisole I-a (0.5mmol,104mg), dimethyl sulfoxide (1.0mmol,78mg) were dissolved in toluene (0.5mL), thionyl chloride (1.0mmol,119mg) was added dropwise, and the reaction was carried out at room temperature (25 ℃ C.) until TLC showed complete reaction of the substrate. The reaction mixture was extracted with water (20mL) and ethyl acetate (20mL × 3), the organic phases were combined, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, added to column chromatography silica gel and evaporated to dryness, and the mixture was separated by column chromatography (petroleum ether) to give 102mg of a colorless liquid with a yield of 85%.1HNMR(600MHz,CDCl3)δ8.29-8.28(m,2H),7.70(dd,J＝6.6,1.8Hz,1H),7.50(d,J＝7.2Hz,1H),7.46(t,J＝7.8Hz,2H),7.37(t,J＝7.8Hz,1H),7.32-7.27(m,2H),2.35(s,3H).13C NMR(150MHz,CDCl3)δ155.3,153.7,131.2,130.4,129.1,128.6,127.3,125.1,123.4,120.1,111.4,109.3,18.5.HRMS(ESI)calcd forC15H13OS+[M+H+]241.0682 and found 241.0689 is II-a.
With 2- (2-phenyl-ethynyl) phenol
In place of 2- ((2-phenyl) -ethynyl) anisole I-a of this example, otherwise as in this example, there was prepared:
2-phenyl-3-methylthiobenzofuran.
Example 2
Preparation of 2- (4-methyl) phenyl-3-methylthiobenzofuran II-b
2- (2- (4-methyl) phenyl) -ethynyl) anisole I-b (0.5mmol,111mg), dimethyl sulfoxide (1.0mmol,78mg) were dissolved in toluene (0.5mL), thionyl chloride (1.0mmol,119mg) was added dropwise and the reaction was carried out at room temperature (25 ℃ C.) until TLC showed complete reaction of the substrate. Extracting the reaction solution with water (20mL) and ethyl acetate (20 mL. times.3), combining the organic phases, washing the organic phase with saturated saline solution, adding anhydrous sodium sulfate for drying, adding the organic phase into column silica gel for drying by distillation, and separating by column chromatography (petroleum ether) to obtain a yellow-green solid of 109mg, wherein the yield is 86% and the melting point is 51-52 ℃.1H NMR(600MHz,CDCl3)δ8.32(dd,J＝7.8,1.2Hz,1H),8.22(d,J＝7.8Hz,1H),8.07(dd,J＝3.6,1.2Hz,1H),7.85-7.82(m,1H),7.55-7.51(m,2H),7.16(dd,J＝5.4,4.8Hz,1H),2.32(s,3H).13C NMR(150MHz,CDCl3)δ160.8,152.5,138.6,135.3,134.0,131.4,131.3,129.9,128.1,126.9,125.5,120.4,108.0,18.6.HRMS(ESI)calcd for C16H15OS+[M+H+]255.0838, found 255.0839, is II-b.
With 2- (2- (4-methoxy) phenyl) -ethynyl) anisole, 2- (2- (4-fluoro) phenyl) -ethynyl) anisole, 2- (2- (4-chloro) phenyl) -ethynyl) anisole, 2- (2- (4-bromo) phenyl) -ethynyl) anisole, 2- (2- (4-trifluoromethyl) phenyl) -ethynyl) anisole, 2- (2- (3-methyl) phenyl) -ethynyl) anisole, 2- (2- (3-methoxy) phenyl) -ethynyl) anisole, 2- (2- (3-fluoro) phenyl) -ethynyl) anisole, 2- (2- (3-chloro) phenyl) -ethynyl) anisole, 2- (4-bromo) phenyl) -ethynyl) anisole, 2, 2- (2- (3-bromo) phenyl) -ethynyl) anisole, 2- (2- (3-trifluoromethyl) phenyl) -ethynyl) anisole, 2- (2- (2-methyl) phenyl) -ethynyl) anisole, 2- (2- (2-methoxy) phenyl) -ethynyl) anisole, 2- (2- (2-fluoro) phenyl) -ethynyl) anisole, 2- (2- (2-chloro) phenyl) -ethynyl) anisole or 2- (2- (2-bromo) phenyl) -ethynyl) anisole were substituted for 2- (2- (4-methyl) phenyl) -ethynyl) anisole of this example, respectively, as in this example, respectively preparing: 2- (4-methoxy) phenyl-3-methylthiobenzofuran, 2- (4-fluoro) phenyl-3-methylthiobenzofuran, 2- (4-chloro) phenyl-3-methylthiobenzofuran, 2- (4-bromo) phenyl-3-methylthiobenzofuran, 2- (4-trifluoromethyl) phenyl-3-methylthiobenzofuran, 2- (3-methyl) phenyl-3-methylthiobenzofuran, 2- (3-methoxy) phenyl-3-methylthiobenzofuran, 2- (3-fluoro) phenyl-3-methylthiobenzofuran, 2- (3-chloro) phenyl-3-methylthiobenzofuran, 2- (4-fluoro) benzofuran, 2- (3-chloro) phenyl-3-methylthiobenzofuran, and mixtures thereof, 2- (3-bromo) phenyl-3-methylthiobenzofuran, 2- (3-trifluoromethyl) phenyl-3-methylthiobenzofuran, 2- (2-methyl) phenyl-3-methylthiobenzofuran, 2- (2-methoxy) phenyl-3-methylthiobenzofuran, 2- (2-fluoro) phenyl-3-methylthiobenzofuran, 2- (2-chloro) phenyl-3-methylthiobenzofuran, or 2- (2-bromo) phenyl-3-methylthiobenzofuran.
Example 3
Preparation of 2- (2-thienyl) -3-methylthiobenzofuran II-c
Figure BDA0002255212740000051
2- (2)- (2-thienyl) -ethynyl) anisole I-c (0.5mmol,107mg), dimethyl sulfoxide (1.0mmol,78mg) were dissolved in toluene (0.5mL), and thionyl chloride (1.0mmol,119mg) was added dropwise and reacted at room temperature (25 ℃) until TLC indicated complete reaction of the substrate. Extracting the reaction solution with water (20mL) and ethyl acetate (20 mL. times.3), combining the organic phases, washing the organic phase with saturated saline solution, adding anhydrous sodium sulfate for drying, adding the organic phase into column silica gel for drying by distillation, and separating by column chromatography (petroleum ether) to obtain a yellow-green solid of 80mg, wherein the yield is 65%, and the melting point is 57-58 ℃.1H NMR(400MHz,CDCl3)δ7.88(dd,J＝8.0,0.8Hz,1H),7.67-7.65(m,1H),7.48-7.46(m,1H),7.42(dd,J＝5.2,1.2Hz,1H),7.32-7.26(m,2H),7.37(t,J＝7.8Hz,1H),7.32-7.27(m,2H),7.13(dd,J＝5.2,4.0Hz,1H),2.38(s,3H).13C NMR(100MHz,CDCl3)δ153.7,152.5,131.8,130.8,127.6,127.4,125.,123.4,119.7,111.3,107.9,18.3.HRMS(ESI)calcd for C13H11OS2 +[M+H+]247.0246, found247.0256, is II-c.
In this example, 2- (2- (2-thienyl) -ethynyl) anisole was replaced with 2- (2- (1-cyclopropyl) ethynyl) anisole or 2- (2- (1-naphthyl) ethynyl) anisole, and otherwise the same as in this example, prepared: 2- (2-cyclopropyl) -3-methylthiobenzofuran or 2- (2-naphthyl) -3-methylthiobenzofuran.
Example 4
Preparation of 2-phenyl-3- (methylthio) -5-methylbenzofuran II-d
Figure BDA0002255212740000052
2- (2-phenyl) -ethynyl-4-methyl-anisole I-d (0.5mmol,121mg), dimethyl sulfoxide (1.0mmol,78mg) were dissolved in toluene (0.5mL), thionyl chloride (1.0mmol,119mg) was added dropwise and the reaction was carried out at room temperature (25 ℃ C.) until TLC showed complete reaction of the substrate. The reaction mixture was extracted with water (20mL) and ethyl acetate (20mL × 3), the organic phases were combined, the organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, the organic phase was evaporated to dryness on silica gel column chromatography, and the white solid was isolated in a yield of 81% at 103mg by column chromatography (ethyl acetate: petroleum ether: 5:95),the melting point is 61-62 ℃.1H NMR(400MHz,CDCl3)δ8.28-8.26(m,2H),8.49-8.44(m,3H),7.37(d,J＝8.4Hz,2H),7.11(dd,J＝8.4,1.2Hz,1H),2.47(s,3H),2.36(s,3H).13C NMR(100MHz,CDCl3)δ155.4,152.2,132.8,131.3,130.5,128.9,128.6,127.3,126.4,119.8,110.9,108.9,21.5,18.5.HRMS(ESI)calcd for C16H15OS+[M+H+]255.0838, found 255.0828 is II-d.
This example was followed by substituting 2- (2-phenyl) -ethynyl-4-methyl-anisole for 2- (2-phenyl) -ethynyl-4-chloro-anisole to prepare: 2-phenyl-3- (methylthio) -5-chlorobenzofuran.
Example 5
2-phenyl-3- ((methyl-d)3) Preparation of thio) benzofurans II-a
Figure BDA0002255212740000061
2- ((2-phenyl) -ethynyl) anisole I-a (0.5mmol,104mg) was dissolved in deuterated dimethyl sulfoxide (0.5mL), thionyl chloride (1.0mmol,119mg) was added dropwise, and the reaction was carried out at room temperature (25 ℃ C.) until TLC indicated complete reaction of the substrate. Extracting the reaction solution with water (20mL) and ethyl acetate (20 mL. times.3), combining the organic phases, washing the organic phase with saturated saline solution, adding anhydrous sodium sulfate for drying, adding the organic phase into column silica gel for drying by distillation, and separating by column chromatography (petroleum ether) to obtain a white solid 99mg with a yield of 81% and a melting point of 69-70 ℃.1H NMR(400MHz,CDCl3)δ8.30-8.27(m,2H),7.72-7.69(m,1H),7.51-7.49(m,3H),7.38(td,J＝7.6,2.0Hz,1H),7.34-7.27(m,2H).13C NMR(100MHz,CDCl3)δ155.3,153.7,131.2,130.4,129.0,128.6,127.3,125.1,123.2,120.1,111.4,109.2.HRMS(ESI)calcd for C15H10D3OS+[M+H+]244.0870, found 244.0879, is II-a'.
With 2- (2- (4-methyl) phenyl) -ethynyl) anisole, 2- (2- (4-methoxy) phenyl) -ethynyl) anisole, 2- (2- (4-fluoro) phenyl) -ethynyl) anisole, 2- (2- (4-chloro) phenyl) -ethynyl) anisole, 2- (2- (4-bromo) phenyl) ethynyl) anisole) -ethynyl) anisole, 2- (2- (4-trifluoromethyl) phenyl) -ethynyl) anisole, 2- (2- (3-methyl) phenyl) -ethynyl) anisole, 2- (2- (3-methoxy) phenyl) -ethynyl) anisole, 2- (2- (3-fluoro) phenyl) -ethynyl) anisole, 2- (2- (3-chloro) phenyl) -ethynyl) anisole, 2- (2- (3-bromo) phenyl) -ethynyl) anisole, 2- (2- (3-trifluoromethyl) phenyl) -ethynyl) anisole, 2- (2- (2-methyl) phenyl) -ethynyl) anisole, 2- (3-trifluoromethyl) phenyl) -ethynyl) anisole, 2- (2-methyl) phenyl) -ethynyl) anisole, and, 2- (2- (2-methoxy) phenyl) -ethynyl) anisole, 2- (2- (2-fluoro) phenyl) -ethynyl) anisole, 2- (2- (2-chloro) phenyl) -ethynyl) anisole, 2- (2- (2-bromo) phenyl) -ethynyl) anisole, 2- (2- (2-thienyl) -ethynyl) anisole, 2- (2- (1-cyclopropyl) ethynyl) anisole, 2- (2- (1-naphthyl) ethynyl) anisole, 2- (2-phenyl) -ethynyl-4-methyl-anisole or 2- (2-phenyl) -ethynyl-4-chloro-anisole in place of the 2- ((2-phenyl) of this example Ethynyl) anisole I-a, otherwise as in this example, was prepared separately: 2- (4-methyl) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (4-methoxy) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (4-fluoro) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (4-chloro) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (4-bromo) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (4-trifluoromethyl) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (3-methyl) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (3-methoxy) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (3-fluoro) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (3-chloro) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (3-bromo) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (3-trifluoromethyl) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (2-methyl) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (2-methoxy) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (2 fluoro) phenyl-3- (methyl-d3) Thiobenzofuran, 2- (2-chloro) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (2-bromo) phenyl-3- (methyl-d)3) Thiobenzofuran, 2- (2-thienyl) -3- (methyl-d3) Thiobenzofuran, 2- (2-cyclopropyl) -3- (methyl-d3) Thiobenzofuran, 2- (2-naphthyl) -3- (methyl-d3) Thiobenzofuran, 2-phenyl-3- ((methyl-d)3) Thio) -5-methylbenzofuran or 2-phenyl-3- ((methyl-d)3) Thio) -5-chlorobenzofuran.

Claims (4)

  1. A method for synthesizing 3-methylthio substituted benzofuran derivatives is characterized by comprising the following steps of: dissolving a compound I and dimethyl sulfoxide in toluene, dropwise adding thionyl chloride, and reacting at room temperature to obtain a 3-methylthio-substituted benzofuran compound (II);
    Figure FDA0002255212730000011
    the compound I is 2- ((2-R)2) -ethynyl) anisole or 2- ((2-R)2) -ethynyl) phenol;
    in the formula:
    R1is a hydrogen atom, a methyl group or a chlorine atom;
    R2is a hydrogen atom, a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-trifluoromethylphenyl group, a 3-methylphenyl group, a 3-methoxyphenyl group, a 3-chlorophenyl group, a 3-bromophenyl group, a 3-trifluoromethylphenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group, a 2-chlorophenyl group, a 2-bromophenyl group, a 2-thienyl group or a cyclopropyl group;
    R3is a hydrogen atom or a methyl group.
  2. 2. The process as set forth in claim 1, characterized in that the molar ratio of compound I to thionyl chloride is 1: 2.
  3. The synthesis method of the 3-methylthio substituted benzofuran derivative is characterized by comprising the following steps of: dissolving the compound I in deuterated dimethyl sulfoxide, dropwise adding thionyl chloride, and reacting at room temperature to obtain a 3-methylthio-substituted benzofuran compound (II');
    Figure FDA0002255212730000012
    the compound I is 2- ((2-R)2) -ethynyl) anisole or 2- ((2-R)2) -ethynyl) phenol;
    in the formula:
    R1is a hydrogen atom, a methyl group or a chlorine atom;
    R2is a hydrogen atom, a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-trifluoromethylphenyl group, a 3-methylphenyl group, a 3-methoxyphenyl group, a 3-chlorophenyl group, a 3-bromophenyl group, a 3-trifluoromethylphenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group, a 2-chlorophenyl group, a 2-bromophenyl group, a 2-thienyl group or a cyclopropyl group;
    R3is a hydrogen atom or a methyl group.
  4. 4. The process as set forth in claim 3, characterized in that the molar ratio of compound I to thionyl chloride is 1: 2.
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