CN115093360B - Synthesis method of indole derivatives - Google Patents
Synthesis method of indole derivatives Download PDFInfo
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- CN115093360B CN115093360B CN202210789173.0A CN202210789173A CN115093360B CN 115093360 B CN115093360 B CN 115093360B CN 202210789173 A CN202210789173 A CN 202210789173A CN 115093360 B CN115093360 B CN 115093360B
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- indole
- thionyl chloride
- phenyl
- cdcl
- dimethyl sulfoxide
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- 150000002475 indoles Chemical class 0.000 title claims abstract description 14
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims abstract description 12
- 238000001308 synthesis method Methods 0.000 title claims abstract description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- KURPPWHPIYBYBS-UHFFFAOYSA-N 2-ethenylaniline Chemical class NC1=CC=CC=C1C=C KURPPWHPIYBYBS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 4
- -1 p-toluenesulfonyl Chemical group 0.000 claims description 10
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 21
- 230000035484 reaction time Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 10
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- LQXHLFGPRYWSLD-UHFFFAOYSA-N BrC1=CC(=C(C=C1)NS(=O)(=O)C1=CC=C(C)C=C1)C(=C)C1=CC=CC=C1 Chemical compound BrC1=CC(=C(C=C1)NS(=O)(=O)C1=CC=C(C)C=C1)C(=C)C1=CC=CC=C1 LQXHLFGPRYWSLD-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- CSSYWWHHYTXGNS-UHFFFAOYSA-N n-[4-chloro-2-(1-phenylethenyl)phenyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(Cl)C=C1C(=C)C1=CC=CC=C1 CSSYWWHHYTXGNS-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- ULFRLSNUDGIQQP-UHFFFAOYSA-N rizatriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CN1C=NC=N1 ULFRLSNUDGIQQP-UHFFFAOYSA-N 0.000 description 1
- 229960000425 rizatriptan Drugs 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- KCFYEAOKVJSACF-UHFFFAOYSA-N umifenovir Chemical compound CN1C2=CC(Br)=C(O)C(CN(C)C)=C2C(C(=O)OCC)=C1CSC1=CC=CC=C1 KCFYEAOKVJSACF-UHFFFAOYSA-N 0.000 description 1
- 229960004626 umifenovir Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
Abstract
The invention discloses a synthesis method of indole derivatives, which comprises the following steps: dissolving raw material o-vinylaniline derivative (II) in dimethyl sulfoxide, dropwise adding thionyl chloride, and reacting to obtain indole derivative (I); the reaction formula is as follows:
Description
Technical field:
the invention relates to a synthetic method of indole derivatives.
The background technology is as follows:
indole derivatives are an important class of heterocyclic compounds, the backbone of which is one of the scaffold structures with distinct advantages in many bioactive and functional molecules as well as in natural products. Many small molecule drugs also contain indole structures such as tadalafil, rizatriptan, fluvastatin, and arbidol. In addition, sulfur-substituted indole derivatives have shown good therapeutic efficacy in the treatment of a number of diseases. Chemical synthesis of indole derivatives has been reported so far, but in these synthetic methods using o-vinylaniline derivatives (II) as raw materials, formation of 2-methylthio-substituted indole derivatives (I) under the combined action of thionyl chloride and dimethyl sulfoxide has not been reported.
The invention comprises the following steps:
the invention aims to overcome the defects of the prior art and provides a synthetic method of indole derivatives which simply realize intramolecular cyclization.
The technical scheme of the invention is summarized as follows:
a synthetic method of indole derivatives comprises the following steps: dissolving raw material o-vinylaniline derivative (II) in dimethyl sulfoxide, dropwise adding thionyl chloride, and reacting to obtain indole derivative (I);
wherein:
R 1 is a hydrogen atom, a chlorine atom, a bromine atom, a methyl group or a trifluoromethyl group;
R 2 phenyl, 3-fluorophenyl or 4-bromophenyl;
R 3 is p-toluenesulfonyl or 4-chlorobenzenesulfonyl;
the molar ratio of the o-vinylaniline derivative (II) to thionyl chloride is preferably 1:4.
The method has the advantages of simple operation, low-cost and easily obtained raw materials, mild reaction conditions, short reaction time, ideal yield and the like.
The specific embodiment is as follows:
thionyl chloride (SOCl) 2 ) Analytically pure thionyl chloride is commercially available.
Dimethyl sulfoxide (DMSO) is commercially available absolute anhydrous dimethyl sulfoxide.
The starting material required in the examples, o-vinylaniline (II), was prepared by the literature reference method. ( (1) Xia, h. -d; zhang, y. -d.; wang, y. -h; zhang, C.org.Lett.2018,20,4052-4056 )
The invention is further illustrated by the following examples.
Example 1
Preparation of 2- (methylthio) -3-phenyl-1-tosyl-1H-indole-l-a
4-methyl-ethyl acetateThe base-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide ll-a (0.5 mmol,174 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 157mg of white solid in 80% yield and melting point 116-118 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.42(d,J＝8.5Hz,1H),7.85(d,J＝8.3Hz,2H),7.54–7.36(m,7H),7.28(s,1H),7.21(d,J＝8.3Hz,2H),2.36(s,3H),2.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.8,138.0,136.1,132.6,131.6,130.1,129.8,129.6,129.5,128.4,127.9,127.3,126.0,123.8,120.1,115.6,21.7,21.4.HRMS(ESI)calcd for C 22 H 19 NNaO 2 S 2 + [M+Na + ]416.0749,found 416.0755.
Example 2
Preparation of 5-chloro-2- (methylthio) -3-phenyl-1-tosyl-1H-indole-b
N- (4-chloro-2- (1-phenylvinyl) phenyl) -4-methylbenzenesulfonamide ll-b (0.5 mmol,192 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then with saturated brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 139mg of white solid with a yield of 65% and a melting point of 148-150 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.34(d,J＝9.0Hz,1H),7.82(d,J＝8.4Hz,2H),7.50–7.44(m,2H),7.41(td,J＝5.9,2.3Hz,4H),7.36(dd,J＝9.0,2.2Hz,1H),7.23(d,J＝8.1Hz,2H),2.37(s,3H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.1,136.3,135.8,132.0,131.4,130.7,130.6,130.0,129.7,129.7,128.5,128.1,127.3,126.0,119.5,116.7,21.7,21.3.HRMS(ESI)calcd for C 22 H 18 ClNNaO 2 S 2 + [M+Na + ]450.0360,found 450.0366.
Example 3
Preparation of 5-bromo-2- (methylthio) -3-phenyl-1-tosyl-1H-indolyl-c
N- (4-bromo-2- (1-phenylvinyl) phenyl) -4-methylbenzenesulfonamide ll-c (0.5 mmol,214 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C, and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 172mg of a white solid with a yield of 73% and a melting point of 139-141 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.28(d,J＝8.7Hz,1H),7.88–7.78(m,2H),7.55(d,J＝1.7Hz,1H),7.52–7.44(m,3H),7.40(tt,J＝7.8,1.6Hz,3H),7.23(d,J＝8.0Hz,2H),2.37(s,3H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.1,136.6,135.8,132.0,131.3,131.2,130.5,130.0,129.7,128.7,128.5,128.1,127.3,122.6,117.4,117.0,21.7,21.3.HRMS(ESI)calcd for C 22 H 18 BrNNaO 2 S 2 + [M+Na + ]493.9855,found 493.9858.
Example 4
Preparation of 6-methyl-2- (methylthio) -3-phenyl-1-tosyl-1H-indole-d
4-methyl-N- (5-methyl-2- (1-phenylvinyl) ethyl)Phenyl) benzenesulfonamide ll-d (0.5 mmol,182 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol, 235 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 179mg of white solid in 88% yield with a melting point of 139-140 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.23(s,1H),7.84(d,J＝8.4Hz,2H),7.48–7.36(m,5H),7.33(d,J＝8.1Hz,1H),7.21(d,J＝8.1Hz,2H),7.09(d,J＝7.4Hz,1H),2.54(s,3H),2.36(s,3H),2.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.7,138.4,136.2,132.8,131.7,130.1,129.8,129.6,128.9,128.3,127.8,127.3,127.1,125.3,119.7,115.6,22.2,21.7,21.5.HRMS(ESI)calcd for C 23 H 21 NNaO 2 S 2 + [M+Na + ]430.0906,found 430.0902.
Example 5
Preparation of 2- (methylthio) -3-phenyl-1-tosyl-6- (trifluoromethyl) -1H-indole-e
4-methyl-N- (2- (1-phenylvinyl) -5- (trifluoromethyl) phenyl) benzenesulfonamide ll-e (0.5 mmol,209 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 113mg of a white solid with a yield of 49% and a melting point of 121-123 ℃. 1 H NMR(600MHz,CDCl 3 )δ8.72(s,1H),7.86(d,J＝8.4Hz,2H),7.53(d,J＝8.3Hz,1H),7.51–7.45(m,3H),7.42(dd,J＝5.5,1.9Hz,3H),7.25(d,J＝9.6Hz,2H),2.38(s,3H),2.27(s,3H). 13 C NMR(151MHz,CDCl 3 )δ145.3,137.0,135.8,132.9,131.9,131.8,130.7,130.0,129.7,128.5,128.2,127.8(q, 2 J C-F ＝32.1Hz),127.5,124.6(q, 1 J C-F ＝270.5Hz),120.4,113.0(q, 4 J C-F ＝4.4Hz),21.6,21.1.HRMS(ESI)calcd for C 23 H 18 F 3 NNaO 2 S 2 + [M+Na + ]484.0623,found 484.0625.
Example 6
Preparation of 3- (3-fluorophenyl) -2- (methylthio) -1-tosyl-1H-indole-l-f
N- (2- (1- (3-fluorophenyl) vinyl) phenyl) -4-methylbenzenesulfonamide ll-f (0.5 mmol,184 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C, and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then with saturated brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 146mg of white solid in 71% yield and 83-84 ℃. 1 H NMR(600MHz,CDCl 3 )δ8.42(d,J＝8.5Hz,1H),7.85(d,J＝8.3Hz,2H),7.42(dd,J＝15.7,7.3Hz,3H),7.28(d,J＝7.5Hz,1H),7.22(d,J＝8.4Hz,3H),7.16(d,J＝9.8Hz,1H),7.09(td,J＝8.4,2.3Hz,1H),2.37(s,3H),2.31(s,3H). 13 C NMR(151MHz,CDCl 3 )δ162.7(d, 1 J C-F ＝244.3Hz),144.9,138.0,136.1,134.8(d, 3 J C-F ＝8.4Hz),130.24(d, 4 J C-F ＝2.0Hz),130.21,129.8(d, 3 J C-F ＝8.4Hz),129.6,129.1,127.3,126.1,125.9,123.9,119.8,117.1(d, 2 J C-F ＝21.8Hz),115.6,114.7(d, 2 J C-F ＝20.9Hz),21.6,21.3.HRMS(ESI)calcd for C 22 H 18 FNNaO 2 S 2 + [M+Na + ]434.0655,found 434.0658.
Example 7
Preparation of 3- (4-bromophenyl) -2- (methylthio) -1-tosyl-1H-indole-g
N- (2- (1- (4-bromophenyl) vinyl) phenyl) -4-methylbenzenesulfonamide ll-g (0.5 mmol,214 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C, and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 186mg of white solid with a yield of 79% and a melting point of 116-117 ℃. 1 H NMR(600MHz,CDCl 3 )δ8.42(d,J＝8.5Hz,1H),7.85(d,J＝8.4Hz,2H),7.59(d,J＝8.4Hz,2H),7.42(dd,J＝16.0,7.6Hz,2H),7.32(d,J＝8.4Hz,2H),7.27(d,J＝7.7Hz,1H),7.22(d,J＝8.2Hz,2H),2.36(s,3H),2.30(s,3H). 13 C NMR(151MHz,CDCl 3 )δ144.9,138.0,136.1,131.8,131.6,130.4,130.0,129.6,129.0,127.3,126.1,123.9,122.0,119.8,115.6,21.6,21.4.HRMS(ESI)calcd for C 22 H 18 BrNNaO 2 S 2 + [M+Na + ]493.9855,found 493.9848.
Example 8
Preparation of 3-methyl-2- (methylsulfanyl) -1-tosyl-1H-indole-H
4-methyl-N- (2- (prop-1-en-2-yl) phenyl) benzenesulfonamide ll-h (0.5 mmol,144 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol,239 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 mL. Times.3), the organic phases were combined, firstThe organic phase was washed with saturated sodium bicarbonate, then with saturated brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 119mg of colorless oily liquid in 72% yield with a melting point of 116-117 ℃. 1 H NMR(400MHz,CDCl 3 )δ8.34(d,J＝8.5Hz,1H),7.78(d,J＝8.4Hz,2H),7.43(d,J＝8.9Hz,1H),7.38(ddd,J＝8.5,7.3,1.4Hz,1H),7.31–7.27(m,1H),7.17(d,J＝8.0Hz,2H),2.38(s,3H),2.33(s,3H),2.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ144.5,138.0,136.3,130.2,129.5,129.2,127.4,127.1,125.8,123.4,119.3,115.5,21.6,20.9,10.2.HRMS(ESI)calcd for C 17 H 17 NNaO 2 S 2 + [M+Na + ]354.0598,found 354.0599.
Example 9
Preparation of 1- ((4-chlorophenyl) sulfonyl) -2- (methylsulfanyl) -3-phenyl-1H-indole-H
4-chloro-N- (2- (1-phenylvinyl) phenyl) benzenesulfonamide ll-h (0.5 mmol,185 mg) was dissolved in dimethyl sulfoxide (1 mL), thionyl chloride (2.0 mmol, 235 mg) was added dropwise at 0deg.C and reacted at 70deg.C until TLC showed complete reaction of the substrate. The reaction was extracted with water (20 mL) and dichloromethane (20 ml×3), the organic phases were combined, washed with saturated sodium bicarbonate and then brine, dried over anhydrous sodium sulfate, and separated by column chromatography (ethyl acetate: petroleum ether=2:98) to give 147mg of white solid in 71% yield and melting point 114-115 ℃. 1 H NMR(600MHz,CDCl 3 )δ8.39(d,J＝8.5Hz,1H),7.90(d,J＝8.6Hz,2H),7.49–7.45(m,3H),7.45–7.38(m,6H),7.28(t,J＝7.6Hz,1H),2.34(s,3H). 13 C NMR(151MHz,CDCl 3 )δ140.4,138.0,137.4,132.4,132.2,130.1,129.69,129.66,129.3,128.7,128.4,128.0,126.2,124.1,120.3,115.5,21.3.HRMS(ESI)calcd for C 21 H 16 ClNNaO 2 S 2 + [M+Na + ]436.0203,found 436.0208.
The foregoing description is only a few examples of the present invention, and is not intended to limit the present invention in any way, and any simple modification, equivalent variations and modification of the above-described examples according to the technical principles of the present invention are within the scope of the present invention.
Claims (2)
1. The synthesis method of the indole derivative is characterized by comprising the following steps of: dissolving raw material o-vinylaniline derivatives in dimethyl sulfoxide, dropwise adding thionyl chloride, and reacting to obtain indole derivatives, wherein the structure of the o-vinylaniline derivatives is shown as follows:
；
the structure of the indole derivative is shown as follows:
；
R 1 is a hydrogen atom, a chlorine atom, a bromine atom, a methyl group or a trifluoromethyl group; r is R 2 Phenyl, 3-fluorophenyl or 4-bromophenyl; r is R 3 Is p-toluenesulfonyl or 4-chlorobenzenesulfonyl.
2. The method for synthesizing indole derivatives according to claim 1, wherein the method comprises the steps of: the molar ratio of the o-vinylaniline derivative to the thionyl chloride is 1:4.
Priority Applications (1)
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| CN112358432A (en) * | 2020-11-02 | 2021-02-12 | 天津大学 | Synthetic method of indole derivatives |
| CN113173899A (en) * | 2021-04-26 | 2021-07-27 | 都创(上海)医药科技股份有限公司 | Method for synthesizing isobenzofuran-1 (3H) -ketone compound |
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| CN110938027A (en) * | 2019-11-20 | 2020-03-31 | 天津大学 | Synthetic method of indole derivatives |
| CN112358432A (en) * | 2020-11-02 | 2021-02-12 | 天津大学 | Synthetic method of indole derivatives |
| CN113173899A (en) * | 2021-04-26 | 2021-07-27 | 都创(上海)医药科技股份有限公司 | Method for synthesizing isobenzofuran-1 (3H) -ketone compound |
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| Divergent synthesis of 2-methylthioindole and 2-unsubstituted indole derivatives mediated by SOCl2 and dimethyl/diethyl sulfoxides;Jingran Zhang，等;《Organic & Biomolecular Chemistry》;第20卷(第40期);第7886-7890页 * |
| Intramolecular cyclization using methylbis(methylthio)sulfonium salts. Part 4. Synthesis of functionalized indoles and dihydroindoles;Capozzi, Giuseppe，等;《Heterocycles》;第24卷(第3期);第583-587页 * |
| Methylbis(methylthio)sulfonium hexachloroantimonate;Capozzi, Giuseppe，等;《e-EROS Encyclopedia of Reagents for Organic Synthesis》;第102页 * |
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