CN107620088A - A kind of method that electrochemical catalytic oxidation synthesizes 3 sulfydryl indole class compounds - Google Patents
A kind of method that electrochemical catalytic oxidation synthesizes 3 sulfydryl indole class compounds Download PDFInfo
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Abstract
The invention discloses a kind of method that electrochemical catalytic oxidation synthesizes 3 sulfydryl indole class compounds, using three-electrode system, negative electrode and anode are graphite electrode, and reference electrode is used as using 0.1mol/L silver nitrate acetonitrile solution；In sodium tetrafluoroborate acetonitrile solution, Benzazole compounds, disulfide and KI are added, after stirring 3~24h of cell reaction under 45~75 DEG C of temperature, 0.2~0.6V constant-pressure conditions, reaction solution is post-treated to obtain the sulfydryl indole class compound of product 3.Synthetic method of the present invention, easy to operate and safe, the sulfydryl indole class compound yield of product 3 is high；Reaction condition is gentleer；The electric energy for having used cleaning is reductant-oxidant, greatly reduces Environmental costs.
Description
Technical field
The present invention relates to a kind of method of electrochemical catalytic oxidation synthesis 3- sulfydryl indole class compounds.
Background technology
3- sulfydryl indole class compounds have extraordinary bioactivity, have the function that in medicine irreplaceable.Its
Received much concern in the notable therapeutic effect for the treatment of cancer, HIV, allergy, heart disease, bacterium infection etc..More than ten years in past, close
Strategy into 3- sulfydryl indole class compounds can be largely classified into two kinds, and one kind is to prepare 3- sulfydryl indole classes by cyclization
Compound；Another kind is to react synthesis 3- sulfydryl indole class compounds by the nucleopilic reagent of Benzazole compounds and sulfur-bearing.
When the nucleopilic reagent using sulfur-bearing is with Benzazole compounds reaction synthesis 3- sulfydryl indole class compounds, main
Sulphur source can be divided into following several：(1) phthalimide of N- virtues vulcanization；(2) sulfinic acid；(3) benzene sulfinic acid sodium salt；(4)
Benzene sulfonyl chloride；(5) disulfide；(6) mercaptan.Most common of which and what is be easy to get is disulfide and mercaptan, but mercaptan compound is general
Foul smelling, effect on environment are very big.In addition, in the nucleopilic reagent and Benzazole compounds reaction synthesis 3- sulfydryl indole classes of sulfur-bearing
In the reaction of compound, transition-metal catalyst, or the oxidant of stoichiometry are often used, is also needed in many cases
Compare harsh reaction condition, these leverage its application in actual production.
In recent years, with the tremendous development of Green Chemistry, electrochemistry formated have become important green synthesis method it
One.Under electrochemical conditions, selected reductant-oxidant is electric energy, is the reductant-oxidant of cleaning green.And in electrification
Learn in reaction system and do not add other oxidants, be advantageous to the separating-purifying of product.Document (Angewandte Chemie
International Edition,2017,56:3009-3013) report using Benzazole compounds and mercaptan as raw material, through straight
The method for connecing electrochemistry formated 3- sulfydryl indole class compounds.But reaction need to be carried out under higher current potential, so easily be caused
The peroxidating of the electropolymerization and mercaptan of Benzazole compounds；And aliphatic mercaptan when making substrate reaction substantially without；In addition,
Mercaptan used in amounts is twice of indoles substrate.
The content of the invention
It is an object of the invention to provide one kind using Benzazole compounds and disulfide as raw material, pass through electrocatalysis oxidation reaction
The method for preparing 3- sulfydryl indole class compounds.
To achieve the above object, the present invention adopts the following technical scheme that：A kind of electrochemical catalytic oxidation synthesis 3- sulfydryls Yin
The method of diindyl class compound, using three-electrode system, negative electrode and anode are graphite electrode, with 0.1mol/L silver nitrate acetonitrile
Solution is as reference electrode；It is characterized in that：In sodium tetrafluoroborate acetonitrile solution, add Benzazole compounds, disulfide and
KI, after stirring 3~24h of cell reaction under 45~75 DEG C of temperature, 0.2~0.6V constant-pressure conditions, reaction solution is located after
Reason obtains product 3- sulfydryl indole class compounds.
Shown in the structural formula such as formula (II) of the reaction substrate Benzazole compounds, the reaction substrate disulfide compound
Structural formula such as formula (III), shown in obtained product structure formula such as formula (I)；
In formula (I) and formula (II), R1For H or C1~C4 alkyl, preferably R1For H or methyl；R2For H, C1~C4 alkyl, benzene
Base or substituted-phenyl, preferably R2For H, methyl or phenyl；R3For for H, F, Cl, Br, NO2, C1~C4 alkyl or C1~C2 alcoxyls
Base, preferably R1For H, Br, methyl or methoxy.
In formula (I) and formula (III), R4Heteroaryl for C1~C4 alkyl, phenyl, the phenyl of substitution, heteroaryl perfume base, substitution is fragrant
Base, naphthyl or substituted naphthyl.Described heteroaryl perfume base can be that ring includes the heteroatomic aromatic radical such as N, O, S.Described takes
The phenyl in generation, the heteroaryl perfume base of substitution and substituted naphthyl refer to that phenyl ring, miscellaneous aromatic rings and naphthalene ring hydrogen are one or more
Substituent substitutes, and described substituent is each independently selected from one of following：Halogen, C1~C4 alkyl, C1-C4 alkoxy,
Amino and hydroxyl.It is preferred that R4For n-propyl, phenyl, halogenophenyl, alkyl-substituted phenyl, alkoxy substituted phenyl, amino substitution
Phenyl, hydroxyl substituted-phenyl, pyridine radicals or thienyl.
The concentration of synthetic method of the present invention, preferably sodium tetrafluoroborate in acetonitrile is 0.05~0.2mol/L.
The quality dosage for recommending acetonitrile is 20~120 times of the reaction substrate Benzazole compounds quality.
Described reaction substrate Benzazole compounds and disulfide, the mol ratio 100 of KI：40~60：2~8, preferably
For 100：45~55：4~6.
It is preferred that described electrolysis temperature is 55~65 DEG C；It is preferred that decomposition voltage is 0.3~0.5V, the reaction time is 5~
15h。
The method of generally reaction solution post processing is：After reaction terminates, solvent is removed under reduced pressure, then carry out column chromatography point
From with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is eluant, eluent, collects the eluent containing target compound, is evaporated off
Solvent produces product 3- sulfydryl indole class compounds.
The synthetic method of the present invention is specifically recommended to be：Reaction uses three-electrode system, and negative electrode and anode are graphite
Electrode, 0.1mol/L silver nitrate acetonitrile solution is as reference electrode.In 0.05~0.2mol/L sodium tetrafluoroborate acetonitrile solutions
In, Benzazole compounds, disulfide and KI are added, electricity is stirred under 55~65 DEG C of temperature, 0.3~0.5V constant-pressure conditions
After 5~15h of solution reaction, solvent is removed under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 it is mixed
Conjunction liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 3- sulfydryl indole class compounds.It is described
The ratio between the amount of material 100 of reaction substrate Benzazole compounds and disulfide, KI：45~55：4~6.
Synthetic method of the present invention, easy to operate and safe, its advantage essentially consists in：
(A) product 3- sulfydryl indoles class compound yield is high.
(B) reaction condition is gentleer.
(C) electric energy for having used cleaning is reductant-oxidant, greatly reduces Environmental costs.
Embodiment
Below by specific embodiment, the invention will be further described, but protection scope of the present invention is not limited to this.
The structural formula of 3- sulfydryl indole class compounds obtained by following embodiments is respectively as shown in formula (1)~(26)：
Embodiment 1：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V is anti-after 6h
It should terminate.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is to wash
De- agent, collects the eluent containing target compound, solvent is evaporated off and produces product 2- methyl -3- thiophenyl -1H- indoles.Separation is received
Rate is 94%.
Embodiment 2：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that voltage is changed to 0.6V, react 5h, 2- methyl -3- thiophenyl -1H- Yin
The separation yield of diindyl is 94%.
Embodiment 3：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that voltage is changed to 0.2V, react 24h, 2- methyl -3- thiophenyls -1H-
The separation yield of indoles is 90%.
Embodiment 4：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that reaction temperature is changed to 45 DEG C, react 12h, and 2- methyl -3- thiophenyls -
The separation yield of 1H- indoles is 92%.
Embodiment 5：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that reaction temperature is changed to 75 DEG C, react 5h, and 2- methyl -3- thiophenyls -
The separation yield of 1H- indoles is 94%.
Embodiment 6：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
For reactions steps with embodiment 1, except that reaction temperature is changed to 65 DEG C, voltage is changed to 0.5V, reacts 7h, 2- first
The separation yield of base -3- thiophenyl -1H- indoles is 93%.
Embodiment 7：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that Diphenyl disulfide ether dosage is changed to 0.6mmol, voltage is changed to 0.3V,
9h is reacted, the separation yield of 2- methyl -3- thiophenyl -1H- indoles is 86%.
Embodiment 8：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that Diphenyl disulfide ether dosage is changed to 0.4mmol, 2- methyl -3- benzene sulphur
The separation yield of base -1H- indoles is 72%.
Embodiment 9：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that Diphenyl disulfide ether dosage is changed to 0.55mmol, iodate potassium application rate changes
For 0.04mmol, the separation yield of 2- methyl -3- thiophenyl -1H- indoles is 88%.
Embodiment 10：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that Diphenyl disulfide ether dosage is changed to 0.45mmol, iodate potassium application rate changes
For 0.06mmol, the separation yield of 2- methyl -3- thiophenyl -1H- indoles is 88%.
Embodiment 11：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that voltage is changed to 0.6V, iodate potassium application rate is changed to 0.8mmol, reaction
The separation yield of 3h, 2- methyl -3- thiophenyl -1H- indoles is 82%.
Embodiment 12：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that iodate potassium application rate is changed to 0.2mmol, react 15h, 2- methyl -3- benzene
The separation yield of sulfenyl -1H- indoles is 86%.
Embodiment 13：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that the acetonitrile solution concentration of sodium tetrafluoroborate is changed to 0.2mol/L reactions
The separation yield of 6h, 2- methyl -3- thiophenyl -1H- indoles is 94%.
Embodiment 14：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that the acetonitrile solution concentration of sodium tetrafluoroborate is changed to 0.05mol/L reactions
The separation yield of 9h, 2- methyl -3- thiophenyl -1H- indoles is 87%.
Embodiment 15：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that the acetonitrile solution dosage of sodium tetrafluoroborate is changed to 35mL, 2- methyl-
The separation yield of 3- thiophenyl -1H- indoles is 94%.
Embodiment 16：The preparation of 2- methyl -3- thiophenyl -1H- indoles (formula 1)
Reactions steps are with embodiment 1, except that the acetonitrile solution dosage of sodium tetrafluoroborate is changed to 6mL, 2- methyl -3-
The separation yield of thiophenyl -1H- indoles is 72%.
Embodiment 17：Preparations of the 2- methyl -3- to chlorophenylsulfanyl -1H- indoles (formula 2)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (rubigan) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- to chlorophenylsulfanyl -1H- Yin
Diindyl.Separation yield is 90%.
Embodiment 18：The preparation of chlorophenylsulfanyl -1H- indoles (formula 3) between 2- methyl -3-
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (chlorphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces chlorophenylsulfanyl -1H- Yin between product 2- methyl -3-
Diindyl.Separation yield is 97%.
Embodiment 19：The preparation of 2- methyl -3- neighbour's chlorophenylsulfanyl -1H- indoles (formula 4)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (Chloro-O-Phenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- neighbour chlorophenylsulfanyl -1H- Yin
Diindyl.Separation yield is 92%.
Embodiment 20：Preparations of the 2- methyl -3- to bromophenylthio -1H- indoles (formula 5)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-bromophenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- to bromophenylthio -1H- Yin
Diindyl.Separation yield is 97%.
Embodiment 21：Preparations of the 2- methyl -3- to chlorophenylthio -1H- indoles (formula 6)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-fluorophenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- to chlorophenylthio -1H- Yin
Diindyl.Separation yield is 90%.
Embodiment 22：Preparations of the 2- methyl -3- to Methoxv-phenylsulfanvl -1H- indoles (formula 7)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-methoxyphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- to methoxybenzene sulphur
Base -1H- indoles.Separation yield is 96%.
Embodiment 23：The preparation of 2- methyl -3- meta-methoxy thiophenyl -1H- indoles (formula 8)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (m-methoxyphenyl) thiophenols (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 7h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- meta-methoxy benzene sulphur
Base -1H- indoles.Separation yield is 90%.
Embodiment 24：The preparation of 2- methyl -3- O-methoxy thiophenyl -1H- indoles (formula 9)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (o-methoxyphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- O-methoxy benzene sulphur
Base -1H- indoles.Separation yield is 94%.
Embodiment 25：Preparations of the 2- methyl -3- to methylphenyl-sulfanyl -1H- indoles (formula 10)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-methylphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- to methylbenzene sulphur
Base -1H- indoles.Separation yield is 96%.
Embodiment 26：The preparation of 2- methyl -3- p-isopropyl thiophenyl -1H- indoles (formula 11)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-isopropyl phenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 7h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- cumic aldehyde sulphur
Base -1H- indoles.Separation yield is 90%.
Embodiment 27：The preparation of 2- methyl -3- p-aminophenyl sulfenyl -1H- indoles (formula 12)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-aminophenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 8h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 2- methyl -3- p-aminophenyl sulphur
Base -1H- indoles.Separation yield is 92%.
Embodiment 28：The preparation of hydroxy benzenes sulfenyl -1H- indoles (formula 13) between 2- methyl -3-
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (hydroxy phenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 12h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces hydroxyphenyl thio between product 2- methyl -3-
Base -1H- indoles.Separation yield is 93%.
Embodiment 29：The preparation of 2- methyl -3- (2- thienyls) sulfenyl -1H- indoles (formula 14)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (2- thienyls) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 9h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, be evaporated off solvent produce product 2- methyl -3- (2- thienyls) sulfenyl -
1H- indoles.Separation yield is 86%.
Embodiment 30：The preparation of 2- methyl -3- (2- pyridine radicals) sulfenyl -1H- indoles (formula 15)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (2- pyridine radicals) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, be evaporated off solvent produce product 2- methyl -3- (2- pyridine radicals) sulfenyl -
1H- indoles.Separation yield is 95%.
Embodiment 31：The preparation of 2- methyl -3- positive rosickyite base -1H- indoles (formula 16)
Acetonitrile solution (15mL), the 2- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), diη-propyl disulfide (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V, after 6h
Reaction terminates.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is
Eluant, eluent, the eluent containing target compound is collected, solvent is evaporated off and produces product 2- methyl -3- positive rosickyite base -1H- indoles.Point
It is 82% from yield.
Embodiment 32：The preparation of 1- methyl -3- thiophenyl -1H- indoles (formula 17)
Acetonitrile solution (15mL), the 1- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V is anti-after 6h
It should terminate.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is to wash
De- agent, collects the eluent containing target compound, solvent is evaporated off and produces product 1- methyl -3- thiophenyl -1H- indoles.Separation is received
Rate is 92%.
Embodiment 33：Preparations of the 1- methyl -3- to chlorophenylsulfanyl -1H- indoles (formula 18)
Acetonitrile solution (15mL), the 1- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (rubigan) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixing
Liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 1- methyl -3- to chlorophenylsulfanyl -1H- Yin
Diindyl.Separation yield is 95%.
Embodiment 34：Preparations of the 1- methyl -3- to methylphenyl-sulfanyl -1H- indoles (formula 19)
Acetonitrile solution (15mL), the 1- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-methylphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 6h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, be evaporated off solvent produce product 1- methyl -3- to Tolylsulfanvl -
1H- indoles.Separation yield is 83%.
Embodiment 35：The preparation of 3- thiophenyl -1H- indoles (formula 20)
Added in 30ml beaker the acetonitrile solutions (15mL) of 0.1mol/L sodium tetrafluoroborates, 1H- indoles (1mmol),
Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V, react after 12h and terminate.
Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is eluant, eluent, is received
Collect the eluent containing target compound, solvent is evaporated off and produces product 3- thiophenyl -1H- indoles.Separation yield is 86%.
Embodiment 36：The preparation of 5- methyl -3- thiophenyl -1H- indoles (formula 21)
Acetonitrile solution (15mL), the 5- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V is anti-after 12h
It should terminate.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is to wash
De- agent, collects the eluent containing target compound, solvent is evaporated off and produces product 5- methyl -3- thiophenyl -1H- indoles.Separation is received
Rate is 95%.
Embodiment 37：Preparations of the 5- methyl -3- to chlorophenylsulfanyl -1H- indoles (formula 22)
Acetonitrile solution (15mL), the 5- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (rubigan) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 12h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 it is mixed
Conjunction liquid is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 5- methyl -3- to chlorophenylsulfanyl -1H-
Indoles.Separation yield is 93%.
Embodiment 38：Preparations of the 5- methyl -3- to methylphenyl-sulfanyl -1H- indoles (formula 23)
Acetonitrile solution (15mL), the 5- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), two (p-methylphenyl) disulfides (0.5mmol) and KI (0.05mmol).60 DEG C, constant potential electricity under 0.4V
Solve, react and terminate after 12h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100
Mixed liquor is eluant, eluent, collects the eluent containing target compound, and solvent is evaporated off and produces product 5- methyl -3- to methylbenzene sulphur
Base -1H- indoles.Separation yield is 94%.
Embodiment 39：The preparation of 5- methoxyl group -3- thiophenyl -1H- indoles (formula 24)
Acetonitrile solution (15mL), the 5- Methyl-1H-indoles of 0.1mol/L sodium tetrafluoroborates are added in 30ml beaker
(1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V is anti-after 12h
It should terminate.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is to wash
De- agent, collects the eluent containing target compound, solvent is evaporated off and produces product 5- methoxyl group -3- thiophenyl -1H- indoles.Separation
Yield is 84%.
Embodiment 40：The preparation of 1- methyl -2- phenyl -3- thiophenyl -1H- indoles (formula 25)
Added in 30ml beaker the acetonitrile solutions (15mL) of 0.1mol/L sodium tetrafluoroborates, 1- methyl -2- phenyl -
1H- indoles (1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.4V,
Reaction terminates after 12h.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 it is mixed
Conjunction liquid is eluant, eluent, collects the eluent containing target compound, be evaporated off solvent produce product 1- methyl -2- phenyl -3- thiophenyls -
1H- indoles.Separation yield is 89%.
Embodiment 41：The preparation of the bromo- 3- thiophenyls -1H- indoles (formula 26) of 5-
The bromo- 1H- indoles of acetonitrile solution (15mL), 5- of 0.1mol/L sodium tetrafluoroborates is added in 30ml beaker
(1mmol), Diphenyl disulfide ether (0.5mmol) and KI (0.05mmol).60 DEG C, potentiostatic deposition under 0.6V is anti-after 20h
It should terminate.Remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is to wash
De- agent, collects the eluent containing target compound, solvent is evaporated off and produces the bromo- 3- thiophenyls -1H- indoles of product 5-.Separation yield
For 67%.
Claims (5)
1. a kind of method of electrochemical catalytic oxidation synthesis 3- sulfydryl indole class compounds, using three-electrode system, negative electrode and sun
Pole is graphite electrode, and reference electrode is used as using 0.1mol/L silver nitrate acetonitrile solution；It is characterized in that：In sodium tetrafluoroborate
In acetonitrile solution, Benzazole compounds, disulfide and KI are added, in 45~75 DEG C of temperature, 0.2~0.6V constant-pressure conditions
After 3~24h of lower stirring cell reaction, reaction solution is post-treated to obtain product 3- sulfydryl indole class compounds；
Shown in the structural formula such as formula (II) of the reaction substrate Benzazole compounds, the knot of the reaction substrate disulfide compound
Structure formula such as formula (III), shown in obtained product structure formula such as formula (I)：
In formula (I) and formula (II), R1For H or C1~C4 alkyl；R2For H, C1~C4 alkyl, phenyl or substituted-phenyl；R3For H, F,
Cl、Br、NO2, C1~C4 alkyl or C1~C2 alkoxies；
In formula (I) and formula (III), R4For C1~C4 alkyl, phenyl, the phenyl of substitution, heteroaryl perfume base, the heteroaryl perfume base of substitution, naphthalene
Base or substituted naphthyl；Described heteroaryl perfume base can be that ring includes the heteroatomic aromatic radical such as N, O, S；Described substituted benzene
Base, the heteroaryl perfume base of substitution and substituted naphthyl refer to phenyl ring, miscellaneous aromatic rings and naphthalene ring hydrogen by one or more substituents
Substitution, described substituent is each independently selected from one of following：Halogen, C1~C4 alkyl, C1-C4 alkoxy, amino and
Hydroxyl.
2. the method as described in claim 1, it is characterised in that：In formula (I) and formula (II), R1For H or methyl；R2For H, methyl
Or phenyl；R3For H, Br, methyl or methoxy；
In formula (I) and formula (III), R4For n-propyl, phenyl, halogenophenyl, alkyl-substituted phenyl, alkoxy substituted phenyl, amino
Substituted-phenyl, hydroxyl substituted-phenyl, pyridine radicals or thienyl.
3. method as claimed in claim 1 or 2, it is characterised in that：Concentration of the sodium tetrafluoroborate in acetonitrile be 0.05~
0.2mol/L；The quality dosage of acetonitrile is 20~120 times of the reaction substrate Benzazole compounds quality；Described reaction bottom
The mol ratio of thing Benzazole compounds and disulfide, KI is 100：45~55：4~6.
4. method as claimed in claim 1 or 2, it is characterised in that：It is preferred that described electrolysis temperature is 55~65 DEG C；It is preferred that electricity
Solution voltage is 0.3~0.5V, and the reaction time is 5~15h.
5. method as claimed in claim 1 or 2, it is characterised in that：The method of reaction solution post processing is：Reaction terminates
Afterwards, remove solvent under reduced pressure, then carry out column chromatography for separation, with ethyl acetate/n-hexane volume ratio 1：100 mixed liquor is elution
Agent, the eluent containing target compound is collected, solvent is evaporated off and produces product 3- sulfydryl indole class compounds.
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| CN113862705A (en) * | 2021-11-18 | 2021-12-31 | 浙江工业大学 | Electrochemical synthesis method of 2-aryl-3-halo-2H-indazole compound |
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