CN107382819A - A kind of preparation method of 3 thioindole class compound - Google Patents
A kind of preparation method of 3 thioindole class compound Download PDFInfo
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- CN107382819A CN107382819A CN201710683089.XA CN201710683089A CN107382819A CN 107382819 A CN107382819 A CN 107382819A CN 201710683089 A CN201710683089 A CN 201710683089A CN 107382819 A CN107382819 A CN 107382819A
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- OPNLYPQYOOHTDG-UHFFFAOYSA-N CC1(C=C(C)N2C)C2=CC=CC1 Chemical compound CC1(C=C(C)N2C)C2=CC=CC1 OPNLYPQYOOHTDG-UHFFFAOYSA-N 0.000 description 1
- QGHRBKXRJLUWCO-UHFFFAOYSA-N CC1C=CC=C2C=CNC12 Chemical compound CC1C=CC=C2C=CNC12 QGHRBKXRJLUWCO-UHFFFAOYSA-N 0.000 description 1
- SFWZZSXCWQTORH-UHFFFAOYSA-N C[n](c(-c1ccccc1)c1)c2c1cccc2 Chemical compound C[n](c(-c1ccccc1)c1)c2c1cccc2 SFWZZSXCWQTORH-UHFFFAOYSA-N 0.000 description 1
- SBOITLSQLQGSLO-UHFFFAOYSA-N C[n](ccc1c2)c1ccc2Br Chemical compound C[n](ccc1c2)c1ccc2Br SBOITLSQLQGSLO-UHFFFAOYSA-N 0.000 description 1
- BRBWMNNHHDSBOY-UHFFFAOYSA-N C[n]1c(cccc2)c2c(Sc(c(F)c(c(F)c2F)F)c2F)c1 Chemical compound C[n]1c(cccc2)c2c(Sc(c(F)c(c(F)c2F)F)c2F)c1 BRBWMNNHHDSBOY-UHFFFAOYSA-N 0.000 description 1
- IKDGLTRLCJTPJX-UHFFFAOYSA-N Cc([n](C)c1ccccc11)c1Sc1ccc(C)cc1C Chemical compound Cc([n](C)c1ccccc11)c1Sc1ccc(C)cc1C IKDGLTRLCJTPJX-UHFFFAOYSA-N 0.000 description 1
- COBWNPLTULHJGN-UHFFFAOYSA-N Cc(cc1)ccc1Sc(c1c2)c[nH]c1ccc2Cl Chemical compound Cc(cc1)ccc1Sc(c1c2)c[nH]c1ccc2Cl COBWNPLTULHJGN-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N Fc1ccc2[nH]ccc2c1 Chemical compound Fc1ccc2[nH]ccc2c1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
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- 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
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Abstract
The present invention relates to technical field of organic synthesis, provide a kind of preparation method of 3 thioindole class compound, phenyl-sulfhydrate compounds and Benzazole compounds are subjected to substitution reaction under the photocatalysis of organic solvent and photochemical catalyst and obtain 3 thioindole class compounds, the photochemical catalyst includes affixing one's name to the one or more in red B, the red Y of administration and Bengal rose red；Preparation method reaction condition provided by the invention is gentle, alkali and oxidant need not be added, participation without transition-metal catalyst, adverse effect of the metal residual for product property can effectively be prevented, improve product property, product yield can be improved simultaneously to 70%, and reaction raw materials synthesize without multistep, simplify technological process.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly to a kind of preparation method of 3- thioindoles class compound.
Background technology
3- substituted indoles are widely present in various natural products, due to good bioactivity, having caused people
Extensive concern.Wherein, 3- thioindoles structure, it is the basic of many natural products, bioactive molecule and drug molecule
Construction unit, and these compounds have an a variety of physiologically actives, such as active anticancer, HIV-resistant activity, antibacterial activity, it is anti-it is fat with
And suppress tubulin polymerization and suppress growth breast cancer cell etc..
In recent years, those skilled in the art have developed the effective ways of some structure 3- thioindole class compounds,
Specific such as palladium, vanadium transition-metal catalysis (Nishimura.T.；Uemura.S.J.Org.Chem.2004,69,
7688-7693；Zhu.D.；Gu.Y.J.Am.Chem.Soc,2015,137,10547–10553).Although Yin is substituted to 3- at present
The study on the synthesis of diindyl class compound has been made significant headway, but the initiation material used in building-up process generally require it is more
Step synthesis, its complex process, and due to using expensive transition metal such as palladium, vanadium etc. to be used as catalyst, can react
Residual fraction metallic element in the product when process and separation, and the introducing of metal ion can reduce 3- thioindole class compounds
Performance and product yield.
The content of the invention
In view of this, it is an object of the invention to provide a kind of preparation method of 3- thioindoles class compound, this method
Participated in without transition metal, required raw material is cheap and easy to get, and one-step synthesis 3- thioindole class compounds can be achieved.
In order to realize foregoing invention purpose, the invention provides following technical scheme：A kind of 3- thioindoles class compound
Preparation method, comprise the following steps：
Phenyl-sulfhydrate compounds and Benzazole compounds are carried out into photocatalysis in the presence of organic solvent and photochemical catalyst to take
Generation reaction obtains 3- thioindole class compounds；
The phenyl-sulfhydrate compounds have structure shown in formula I：
The Benzazole compounds have structure shown in formula II：
The 3- thioindoles class compound has structure shown in formula III：
R in the formula I1For the phenyl of the phenyl of methoxy substitution, alkyl-substituted phenyl or halogen substitution；
R in the formula II2For hydrogen, alkyl, halogen, methoxyl group, nitro, itrile group, methylol, aminomethyl or trifluoromethyl；
R3For hydrogen, alkyl, aminomethyl, aminoethyl, formoxyl or N, N- dimethyl；
R4For hydrogen, alkyl, aminomethyl, methylol, phenyl or tolyl；
The photochemical catalyst includes affixing one's name to the one or more in red B, the red Y of administration and Bengal rose red.
Preferably, the R1And R2In halogen independently be F, Cl or Br.
Preferably, in the formula I R1 be p-methoxyphenyl, a fluorophenyl, o-fluorophenyl, p-fluorophenyl, rubigan,
Between chlorphenyl, p-bromophenyl, 2,3,4,5,6- pentafluorophenyl groups, 2,5- dichlorophenyls, the chloro- 4- fluorophenyls of 2-, the double (fluoroforms of 3,5-
Base) phenyl, p-methylphenyl, an aminomethyl phenyl, 4- isopropyl phenyls or 3,4- 3,5-dimethylphenyls.
Preferably, the organic solvent is polar organic solvent.
Preferably, the polar organic solvent includes dimethyl sulfoxide (DMSO), DMF, toluene, ethanol, acetonitrile
With the one or more in dichloromethane.
Preferably, the ratio between amount of material of the phenyl-sulfhydrate compounds, Benzazole compounds and photochemical catalyst be 1.5~
2.0：1：0.01~0.1.
Preferably, the concentration of the phenyl-sulfhydrate compounds in organic solvent is 1.5~2mol/L.
Preferably, the photocatalysis substitution reaction is carried out under air atmosphere or inert atmosphere.
Preferably, the wavelength of light source is 200~1000nm in the photocatalysis substitution reaction.
Preferably, the reaction temperature of the photocatalysis substitution reaction is 15~30 DEG C；
The reaction time of the photocatalysis substitution reaction is 6~24h.
The invention provides a kind of preparation method of 3- thioindoles class compound, by phenyl-sulfhydrate compounds and indoles
Compound carries out photocatalysis substitution reaction in the presence of organic solvent and photochemical catalyst and obtains 3- thioindole class compounds；This hair
The synthetic method of the 3- thioindole class compounds of bright offer can be carried out under conditions of room temperature, anaerobic agent, alkali-free, not had
Any catalyst containing transition metal ions is added, can effectively prevent metal residual for 3- thioindole class compounds
Performance adverse effect, product yield reaches 70%；And the present invention directly uses phenyl-sulfhydrate compounds as reaction reagent,
Synthesized without multistep, it is simple easy, it is cheap, it is good to functional group adaptability, it is environment-friendly to substrate wide adaptability, have
Good prospects for commercial application.
Brief description of the drawings
The present invention is further detailed explanation with reference to the accompanying drawings and detailed description.
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 1；
Fig. 2 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 1；
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 2；
Fig. 4 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 2；
Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 3；
Fig. 6 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 3；
Fig. 7 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 4；
Fig. 8 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 4；
Fig. 9 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 5；
Figure 10 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 5；
Figure 11 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 6；
Figure 12 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 6；
Figure 13 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 7；
Figure 14 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 7；
Figure 15 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 8；
Figure 16 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 8；
Figure 17 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 9；
Figure 18 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 9；
Figure 19 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 10；
Figure 20 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 10；
Figure 21 is the hydrogen nuclear magnetic resonance spectrogram of the products obtained therefrom of the embodiment of the present invention 11；
Figure 22 is the carbon-13 nmr spectra figure of the products obtained therefrom of the embodiment of the present invention 11.
Embodiment
The invention provides a kind of preparation method of 3- thioindoles class compound, comprise the following steps：
Phenyl-sulfhydrate compounds and Benzazole compounds are carried out into photocatalysis in the presence of organic solvent and photochemical catalyst to take
Generation reaction obtains 3- thioindole class compounds；
The phenyl-sulfhydrate compounds have structure shown in formula I：
The Benzazole compounds have structure shown in formula II：
The 3- thioindoles class compound has structure shown in formula III：
R in the formula I1For the phenyl of the phenyl of methoxy substitution, alkyl-substituted phenyl or halogen substitution；
R in the formula II2For hydrogen, alkyl, halogen, methoxyl group, nitro, itrile group, methylol, aminomethyl or trifluoromethyl；
R3For hydrogen, alkyl, aminomethyl, aminoethyl, formoxyl or N, N- dimethyl；
R4For hydrogen, alkyl, aminomethyl, methylol, phenyl or tolyl；
The photochemical catalyst includes affixing one's name to the one or more in red B, the red Y of administration and Bengal rose red.
Phenyl-sulfhydrate compounds and Benzazole compounds are carried out light by the present invention in the presence of organic solvent and photochemical catalyst
Catalysis substitution reaction obtains 3- thioindole class compounds.
In the present invention, the phenyl-sulfhydrate compounds have structure shown in formula I, R described in formula I1For methoxy substitution
The phenyl of phenyl, alkyl-substituted phenyl or halogen substitution；The phenyl of the methoxy substitution be preferably p-methoxyphenyl or
4- methoxyphenyls；The alkyl-substituted phenyl is preferably the alkyl-substituted phenyl of 1~5 carbon atom, can be specially pair
Aminomethyl phenyl, an aminomethyl phenyl, 4- isopropyl phenyls or 3,4- 3,5-dimethylphenyls；The phenyl of the halogen substitution is preferably F, Cl
Or Br substitution phenyl, can be specially between fluorophenyl, o-fluorophenyl, p-fluorophenyl, rubigan, a chlorphenyl, p-bromophenyl,
The chloro- 4- fluorophenyls of 2,3,4,5,6- pentafluorophenyl groups, 2,5- dichlorophenyls, 2- or double (trifluoromethyl) phenyl of 3,5-.
In the present invention, the structure of formula I is more preferably：
In the present invention, the Benzazole compounds have a structure shown in formula II, R in the formula II2Can be with substituted benzene ring
Hydrogen on upper optional position carbon atom；In the present invention, R2The position of substituent is preferably 4,5,6,7 carbon atoms (with N position
1 is set to, counterclockwise).
In the present invention, R described in formula II2For hydrogen, alkyl, halogen, methoxyl group, nitro, itrile group, methylol, aminomethyl
Or trifluoromethyl；The alkyl is preferably the alkyl of 1~5 carbon atom, can be specially methyl, ethyl or propyl group；The halogen
Preferably F, Cl or Br.
In the present invention, the R3For hydrogen, alkyl, aminomethyl, aminoethyl, formoxyl or N, N- dimethyl；The alkyl
The alkyl of preferably 1~5 carbon atom, can be specially methyl, ethyl or propyl group；The halogen is preferably F, Cl or Br；
The R4For hydrogen, alkyl, aminomethyl, methylol, phenyl or tolyl；The alkyl is preferably 1~5 carbon atom
Alkyl, can be specially methyl, ethyl or propyl group.
In the present invention, the structure of formula II is more preferably：
In the present invention, the organic solvent is preferably polar organic solvent；The polar organic solvent preferably includes two
One or more in methyl sulfoxide, N,N-dimethylformamide, toluene, ethanol, acetonitrile and dichloromethane；The preferred pole of the present invention
Property organic solvent can increase the dissolubility of reaction raw materials relative to non-polar organic solvent.
The present invention does not have particular/special requirement to the source of the phenyl-sulfhydrate compounds, Benzazole compounds and organic solvent, adopts
With commercially available prod.
The present invention adds photochemical catalyst after preferably mixing phenyl-sulfhydrate compounds, Benzazole compounds and organic solvent；
In the present invention, the ratio between amount of material of the phenyl-sulfhydrate compounds, Benzazole compounds and photochemical catalyst is preferably 1.5~2：1：
0.01~0.1；More preferably 1.6~1.8：1：0.02~0.05, most preferably 1.7：1：0.03.
In the present invention, the concentration of the phenyl-sulfhydrate compounds in organic solvent is 1.5~2mol/L, more preferably
1.6~1.8mol/L, most preferably 1.7mol/L.
In the present invention, the photocatalysis substitution reaction is preferably carried out under air atmosphere or inert atmosphere；The inertia
Atmosphere is preferably nitrogen atmosphere or argon gas atmosphere.Photocatalysis substitution reaction of the present invention does not occur instead under vacuum
Should.
In the present invention, the photocatalysis substitution reaction is carried out under the conditions of light irradiation, and the wavelength of irradiation light source is excellent
Elect 200~1000nm, more preferably 300~800nm, most preferably 500nm as.
In the present invention, the reaction temperature of the photocatalysis substitution reaction is preferably 15~30 DEG C, more preferably 20~25
℃。
In the present invention, the reaction time of the photocatalysis substitution reaction is preferably 6~24h, more preferably 10~20h,
Most elect 15~18h as.
The present invention does not have particular/special requirement to device used in photocatalysis substitution reaction, preferably using equipped with stirring magneton
Reaction bulb, if expanding as industrial production, the corresponding device that can industrially realize of selection, in the present invention, specifically
Reactor may be selected.
After the substitution reaction terminates, the reaction product of preferred pair photocatalysis substitution reaction of the present invention is purified, and is obtained
To 3- thioindole class pure compounds；
In the present invention, the preferred column chromatography purification of the purification；In the present invention, the eluent of the column chromatography is preferably
The mixed solvent of petroleum ether and ethyl acetate, the volume ratio of the in the mixed solvent petroleum ether and ethyl acetate is preferably 5~30：
1, more preferably 10~20：1, most preferably 15：1.
The reaction mechanism of the present invention is specific as follows：
Under illumination condition, photochemical catalyst (RB) produces excited state species RB, at the same time reaction atmosphere such as O2Pass through
Energy transfer produces its excitation state1O2；In this process, excitation state RB returns to its ground state RB.Generated1O2From sulphur
Hydrogen atom is extracted in phenolic compound 1 to obtain sulfenyl free radical.Sulfydryl free radical A or disulfide B and compound 2 occur
Electrophilic addition generates intermediate C, and intermediate C, which is oxidized, obtains cationic intermediates D, and it is final by obtaining that intermediate D loses proton
Product 3- thioindole class compounds.
The preparation method of 3- thioindoles class compound provided by the invention is carried out at ambient temperature, reaction condition temperature
With, it is not necessary to alkali and oxidant are added, safe operation is simple, the participation of no transition-metal catalyst, can effectively prevent metal
The adverse effect of the performance for 3- thioindole class compounds is remained, improves product property, while product yield can improve
To 70%, and reaction raw materials are synthesized without multistep, simple and easy to get, cheap, good to functional group adaptability, and substrate is adapted to
Property is wide, environment-friendly, has good prospects for commercial application.
The preparation method of 3- thioindoles class compound provided by the invention is carried out specifically with reference to embodiment
It is bright, but they can not be interpreted as limiting the scope of the present invention.
Embodiment 1
0.1mmol 1- methyl indols are added in reaction bulb, 0.2mmol adds to methoxybenzenethiol, 0.02mmol Meng
Rose-red, 0.1ml dichloromethane are drawn, under the irradiation of 400nm light sources, stirring reaction 20 hours under 22 DEG C of temperature conditionss, reaction terminates
Afterwards by column chromatographic isolation and purification, the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 24：1, obtain after purification
Target product, yield 64%.The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.62 (d, J=8.0Hz, 1H), δ=7.35 (d, J=8.0Hz, 1H), δ=
7.29 (d, J=8.0Hz, 1H), δ=7.24 (d, J=8.0Hz, 1H), δ=7.17-7.10 (m, 3H), δ=6.71-6.71 (m,
2H), δ=3.81 (s, 3H), δ=3.71 (s, 3H)；
13C NMR(100MHz,CDCl3) δ=157.7,137.5,134.5,128.4,119.7,114.5,109.7,
102.3,55.3,33.1；
MS(EI,70eV)：M/z (%)=269 (M+), 254,237,222,210,162,135,120,102 (100).
As depicted in figs. 1 and 2, wherein Fig. 1 is the products obtained therefrom of the embodiment of the present invention 1 to the structural characterization spectrogram of products therefrom
Hydrogen spectrogram；Fig. 2 is the carbon spectrogram of the products obtained therefrom of the embodiment of the present invention 1.
It can be seen from data above and spectrum analysis, products therefrom is target product, and its structure is as follows：
Embodiment 2
0.2mmol1- methyl indols, 0.3mmol are added in reaction bulb to fluoro thiophenol, the 0.002mmol red Y of administration,
0.2ml dichloromethane, under the irradiation of 350nm light sources, for stirring reaction after 6 hours, reaction passes through column chromatography after terminating under the conditions of 26 DEG C
Isolate and purify, the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 8：1, target product after purification is obtained, is produced
Rate 30%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.58 (d, J=8Hz, 1H), δ=7.36 (d, J=8Hz, 1H), δ=
7.30-7.26 (m, 2H), δ=7.17-7.14 (m, 1H), δ=7.08-7.05 (m, 2H), δ=6.86-6.82 (m, 2H), δ=
3.80(s,3H)；
13C NMR(100MHz,CDCl3) δ=162.1,159.7,137.6,134.9,134.5,129.6,127.8,
127.7,122.7,120.6,119.6,115.8,115.6,109.8,101.4,33.1；
MS(EI,70eV)：M/z (%)=257 (M+), 242,225,183,162,121 (100).
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 3
0.2mmol1- methyl indols, the chloro- 4- fluoro thiophenols of 0.4mmol2-, 0.008mmol administration are added in reaction bulb
Red B, 0.2ml dimethyl sulfoxide (DMSO), under the irradiation of 450nm light sources, after 24 hours, reaction passes through stirring reaction after terminating under the conditions of 22 DEG C
Column chromatographic isolation and purification, obtains target product, and the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 25：1, obtain
Target product after purification, yield 66%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.55 (d, J=8Hz, 1H), δ=7.38 (d, J=8Hz, 1H), δ=
7.32-7.28 (m, 2H), δ=7.18-7.15 (m, 1H), δ=7.09-7.06 (m, 1H), δ=6.65-6.59 (m, 2H), δ=
3.82(s,3H)；
13C NMR(100MHz,CDCl3) δ=161.3,158.9,137.7,135.6,134.2,130.4,130.3,
129.6,127.6,127.5,122.9,120.8,119.5,116.9,116.6,114.5,114.3,110.0,98.9,33.3；
MS(EI,70eV)：M/z (%)=291.1,276.1,256.1,241.1,223.2,183.1,162.1,145.9,
128.0,117.2,104.2。
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 4
0.2mmol1- methyl indols, 0.3mmol2,3,4,5,6- phenyl-pentafluoride thiophenols, 0.004mmol are added in reaction bulb
Red Y, 0.2ml toluene of administration, under the irradiation of 200nm light sources, stirring reaction after 6 hours under the conditions of 24 DEG C, reaction passes through post after terminating
Chromatography purifies, and obtains target product, and the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 5：1, obtain pure
Target product after change, yield 26%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.77 (d, J=8Hz, 1H), δ=7.38 (s, 1H), δ=7.23 (d, J=
7.2Hz, 1H), δ=7.24-7.18 (m, 2H), δ=3.75 (s, 3H)；
13C NMR(100MHz,CDCl3) δ=148.6,146.1,142.7,140.1,138.9,136.9,135.8,
129.5,122.7,120.9,119.2,109.8,99.8,33.1；
MS(EI,70eV)：M/z (%)=329 (M+), 314,296,279,269,255,237,224,211,162,139,
121,102(100)。
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 5
0.2mmol1- methyl indols, double (trifluoromethyl) benzenethiols of 0.35mmol3,5- are added in reaction bulb,
0.002mmol red B, 0.2ml dichloromethane of administration, under the irradiation of 600nm light sources, stirring reaction is after 10 hours under the conditions of 24 DEG C, instead
By column chromatographic isolation and purification after should terminating, the volume of target product, column chromatography eluent petrochina ether and ethyl acetate is obtained
Than for 5：1, obtain target product after purification, yield 34%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.53 (d, J=8Hz, 2H), δ=7.47 (s, 2H), δ=7.42 (d, J=
8Hz, 1H), δ=7.38 (s, 1H), δ=7.35-7.31 (m, 1H), δ=7.21-7.18 (m, 1H), δ=3.89 (s, 3H)；
13C NMR(100MHz,CDCl3)：δ=143.9,137.7,135.5,132.3,132.0,131.7,131.3,
129.1,125.1,124.5,123.1,121.1,119.1,118.3,110.1,97.6,33.3；
MS(EI,70eV)：M/z (%)=375 (M+), 360,343,291,162,121 (100).
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 6
Add 0.15mmol1 in reaction bulb, 2- dimethyl indoles, 0.25mmol to methylbenzene phenyl-sulfhydrate, 0.002mmol's
Bengal rose red, 0.15ml ethanol, under the irradiation of 800nm light sources, stirring reaction is after 24 hours under the conditions of 24 DEG C, after reaction terminates
By column chromatographic isolation and purification, target product is obtained, the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 28：1,
Obtain target product after purification, yield 71%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.57 (d, J=8Hz, 1H), δ=7.25 (d, J=8Hz, 1H), δ=
7.20-7.16 (m, 1H), δ=7.11-7.08 (m, 1H), δ=6.92 (s, 3H), δ=3.62 (s, 3H), δ=2.44 (s, 3H),
δ=2.20 (s, 3H)；
13C NMR(100MHz,CDCl3) δ=142.8,137.1,136.3,134.3,129.9,129.6,125.8,
121.8,120.5,119.0,109.1,98.6,30.3,20.9,10.9；
MS(EI,70eV)：M/z (%)=267 (M+), 252,235,219,176,144,132 (100).
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 7
0.15mmol7- methyl indols are added in reaction bulb, 0.3mmol adds to methylbenzene phenyl-sulfhydrate, 0.002mmol Meng
Rose-red, 0.15ml acetonitriles are drawn, under the irradiation of 400nm light sources, after 20 hours, reaction passes through stirring reaction after terminating under the conditions of 25 DEG C
Column chromatographic isolation and purification, obtains target product, and the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 20：1, obtain
Target product after purification, yield 62%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=8.24 (s, 1H), δ=7.45 (d, J=7.2Hz, 1H), δ=7.36 (d, J
=2.8Hz, 1H), δ=7.05-7.00 (m, 4H), δ=6.94 (d, J=8Hz, 2H), δ=2.45 (s, 3H), δ=2.22 (s,
3H)；
13C NMR(100MHz,CDCl3) δ=136.1,135.6,134.6,130.3,129.5,128.8,126.3,
123.5,121.0,120.8,117.4,103.8,20.9,16.5；
MS(EI,70eV)：M/z (%)=253 (M+), 237,220,205,178,162,151,134,118 (100).
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 8
0.15mmol indoles, 0.25mmol are added in reaction bulb to methylbenzene phenyl-sulfhydrate, 0.002mmol bengal rose
Red, 0.15ml acetonitriles, under the irradiation of 460nm light sources, for stirring reaction after 15 hours, reaction passes through column chromatography after terminating under the conditions of 22 DEG C
Isolate and purify, obtain target product, the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 15：1, obtain after purification
Target product, yield 47%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=8.32 (s, 1H), δ=7.62 (d, J=8Hz, 1H), δ=7.43 (d, J=
2.8Hz, 1H), δ=7.40 (d, J=8Hz, 1H), δ=7.25-7.22 (m, 1H), δ=7.17-7.13 (m, 1H), δ=7.04-
6.95 (m, 1H), δ=2.24 (s, 3H)；
13C NMR(100MHz,CDCl3) δ=136.5,135.5,134.7,130.4,129.5,129.1,126.3,
123.0,120.6,119.7,111.6,103.5,20.9；
MS(EI,70eV)：M/z (%)=239 (M+), 223,207,179,165,148,121 (100).
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 9
0.1mmol1- methyl -2-phenylindone, 0.2mmol are added in reaction bulb to methylbenzene phenyl-sulfhydrate, 0.004mmol
Red B, 0.1ml acetonitrile of administration, under the irradiation of 365nm light sources, stirring reaction after 8 hours under the conditions of 30 DEG C, reaction passes through post after terminating
Chromatography purifies, and obtains target product, and the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 10：1, obtain pure
Target product after change, yield 34%.
The structural characterization data of products therefrom are as follows：
1H NMR(400MHz,CDCl3)：δ=7.64 (d, J=7.6Hz, 1H), δ=7.38 (d, J=8.4Hz, 6H), δ=
7.30-7.26 (m, 1H), δ=7.18-7.14 (m, 1H), δ=6.96-6.90 (m, 4H), δ=3.67 (s, 3H), δ=2.20
(s,3H)；
13C NMR(100MHz,CDCl3) δ=145.8,137.7,136.4,134.2,130.7,130.6,129.9,
129.5,128.8,128.3,125.9,122.9,121.0,119.9,109.8,100.2,31.8,21.0；
MS(EI,70eV)m/z 329.3,314.2,297.2,281.2,252.1,237.1,223.1,204.2,178.2,
165.0,152.1,139.2,120.1,103.1。
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 10
0.15mmol5- chloro-indoles, 0.3mmol are added in reaction bulb to methylbenzene phenyl-sulfhydrate, the 0.01mmol red B of administration,
0.2ml acetonitriles, under the irradiation of 465nm light sources, for stirring reaction after 12 hours, reaction passes through column chromatography for separation after terminating under the conditions of 15 DEG C
Purifying, obtains target product, and the volume ratio of column chromatography eluent petrochina ether and ethyl acetate is 5：1, obtain mesh after purification
Mark product, yield 38%.
The structural characterization data of products therefrom are as follows：
1H NMR (400MHz, DMSO) δ 11.87 (d, J=18Hz, 1H), 7.84 (d, J=2.8Hz, 1H), 7.51 (d, J
=8.4Hz, 1H), 7.33 (s, 1H), 7.19-7.17 (m, 1H), 7.03 (d, J=8Hz, 2H), 6.95 (d, J=8Hz, 2H),
2.20(s,3H)ppm；
13CNMR(100MHz,DMSO)δ135.7,135.4,134.9,134.4,131.7,130.4,130.1,126.4,
125.3,122.6,117.8,114.5,100.5,20.8ppm；
MS(EI,70eV)m/z 273.1,258.0,238.1,223.1,205.1,182.1,155.0,136.6,123.0,
111.5。
Infer that the structure of products therefrom is as follows according to data above：
Embodiment 11
0.15mmol6- fluoro indoles, 0.3mmol are added in reaction bulb to methylbenzene phenyl-sulfhydrate, 0.003mmol Bangladesh
Rose-red, 0.15mlN, dinethylformamide, under the irradiation of 365nm light sources, stirring reaction is after 16 hours under the conditions of 24 DEG C, reaction
By column chromatographic isolation and purification after end, the volume ratio of target product, column chromatography eluent petrochina ether and ethyl acetate is obtained
For 20：1, obtain target product after purification, yield 54%.
The structural characterization data of products therefrom are as follows：
1H NMR (400MHz, DMSO) δ 11.71 (d, J=22.4Hz, 1H), 7.74 (d, J=2.4Hz, 1H), 7.35-
7.32 (m, 1H), 7.35-7.32 (m, 1H), 7.27-7.24 (m, 1H), 7.22 (s, 2H), 7.02 (d, J=8Hz, 2H), 6.94
(d, J=8.4Hz, 2H), 2.19 (s, 3H) ppm；
13CNMR(100MHz,DMSO)δ135.5,134.8,133.2,130.6,130.4,130.0,126.4,125.7,
120.0,109.2,108.8,101.0,99.0,98.7,20.8ppm；
MS(EI,70eV)m/z 257.1,241.1,225.1,209.1,166.0,139.0,120.9,107.1。
Infer that the structure of products therefrom is as follows according to data above：
As seen from the above embodiment, it is only the preferred embodiment of the present invention that the present invention is described above, it is noted that for
For those skilled in the art, under the premise without departing from the principles of the invention, can also make it is some improvement and
Retouching, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of 3- thioindoles class compound, comprises the following steps：
By with the phenyl-sulfhydrate compounds of structure shown in formula I and the Benzazole compounds with structure shown in formula II in organic solvent
With progress photocatalysis substitution reaction in the presence of photochemical catalyst, the 3- thioindole class chemical combination with structure shown in formula III is obtained
Thing；
R in the formula I1For the phenyl of the phenyl of methoxy substitution, alkyl-substituted phenyl or halogen substitution；
R in the formula II2For hydrogen, alkyl, halogen, methoxyl group, nitro, itrile group, methylol, aminomethyl or trifluoromethyl；
R3For hydrogen, alkyl, aminomethyl, aminoethyl, formoxyl or N, N- dimethyl；
R4For hydrogen, alkyl, aminomethyl, methylol, phenyl or tolyl；
The photochemical catalyst includes affixing one's name to the one or more in red B, the red Y of administration and Bengal rose red.
2. preparation method according to claim 1, it is characterised in that the R1And R2In halogen independently be F, Cl or
Br。
3. preparation method according to claim 1, it is characterised in that R in the formula I1For p-methoxyphenyl, a fluorobenzene
Base, o-fluorophenyl, p-fluorophenyl, rubigan, a chlorphenyl, p-bromophenyl, 2,3,4,5,6- pentafluorophenyl groups, 2,5- dichloro-benzenes
The chloro- 4- fluorophenyls of base, 2-, 3,5- double (trifluoromethyl) phenyl, p-methylphenyl, an aminomethyl phenyl, 4- isopropyl phenyls or 3,
4- 3,5-dimethylphenyls.
4. preparation method according to claim 1, it is characterised in that the organic solvent is polar organic solvent.
5. preparation method according to claim 4, it is characterised in that the polar organic solvent include dimethyl sulfoxide (DMSO),
One or more in N,N-dimethylformamide, toluene, ethanol, acetonitrile and dichloromethane.
6. preparation method according to claim 1, it is characterised in that the phenyl-sulfhydrate compounds, Benzazole compounds with
The ratio between amount of material of photochemical catalyst is 1.5~2.0：1：0.01~0.1.
7. the preparation method according to claim 1 or 4, it is characterised in that the phenyl-sulfhydrate compounds are in organic solvent
Concentration be 1.5~2mol/L.
8. preparation method according to claim 1, it is characterised in that the photocatalysis substitution reaction is in air atmosphere or lazy
Carried out under property atmosphere.
9. the preparation method according to claim 1 or 8, it is characterised in that the ripple of light source in the photocatalysis substitution reaction
A length of 200~1000nm.
10. preparation method according to claim 1, it is characterised in that the reaction temperature of the photocatalysis substitution reaction is
15~30 DEG C；
The reaction time of the photocatalysis substitution reaction is 6~24h.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109369645A (en) * | 2018-10-31 | 2019-02-22 | 西北大学 | A kind of green synthesis method of the 3- arylthio -7- azaindole compounds of base catalysis |
| CN111205215A (en) * | 2020-02-23 | 2020-05-29 | 苏州大学 | Application of copper dichloride dihydrate in photocatalysis reaction of indole compounds and thiocyanate compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558020A (en) * | 2011-12-12 | 2012-07-11 | 温州大学 | Method for synthesizing 3-aryl sulfydryl indole compound |
| CN104945305A (en) * | 2015-07-03 | 2015-09-30 | 北京石油化工学院 | Method for achieving indole derivative selective aromatic thiolation |
-
2017
- 2017-08-11 CN CN201710683089.XA patent/CN107382819A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558020A (en) * | 2011-12-12 | 2012-07-11 | 温州大学 | Method for synthesizing 3-aryl sulfydryl indole compound |
| CN104945305A (en) * | 2015-07-03 | 2015-09-30 | 北京石油化工学院 | Method for achieving indole derivative selective aromatic thiolation |
Non-Patent Citations (1)
| Title |
|---|
| WEI GUO ET AL.: "Photocatalytic direct C–S bond formation: facile access to 3-sulfenylindoles via metal-free C-3 sulfenylation of indoles with thiophenols", 《RSC ADV.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109369645A (en) * | 2018-10-31 | 2019-02-22 | 西北大学 | A kind of green synthesis method of the 3- arylthio -7- azaindole compounds of base catalysis |
| CN109369645B (en) * | 2018-10-31 | 2021-08-24 | 西北大学 | Base-catalyzed green synthesis method of 3-arylthio-7-azaindole compound |
| CN111205215A (en) * | 2020-02-23 | 2020-05-29 | 苏州大学 | Application of copper dichloride dihydrate in photocatalysis reaction of indole compounds and thiocyanate compounds |
| CN111205215B (en) * | 2020-02-23 | 2021-11-09 | 苏州大学 | Application of copper dichloride dihydrate in photocatalysis reaction of indole compounds and thiocyanate compounds |
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