CN108440375A - Using disulfide as the catalysis oxidation synthetic method of the 3- sulfydryl indole class compounds of sulphur source - Google Patents
Using disulfide as the catalysis oxidation synthetic method of the 3- sulfydryl indole class compounds of sulphur source Download PDFInfo
- Publication number
- CN108440375A CN108440375A CN201810343486.7A CN201810343486A CN108440375A CN 108440375 A CN108440375 A CN 108440375A CN 201810343486 A CN201810343486 A CN 201810343486A CN 108440375 A CN108440375 A CN 108440375A
- Authority
- CN
- China
- Prior art keywords
- formula
- substituted
- reaction
- phenyl
- indoles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 CC(C1C=C*(SC2=CNC3=CC=CC=CC23)=C)[C@@]1F Chemical compound CC(C1C=C*(SC2=CNC3=CC=CC=CC23)=C)[C@@]1F 0.000 description 8
- KUMOSZCIHPSDAK-UHFFFAOYSA-N CC1=CC=CC=C2C(/S=C(/C=CC=C3)\C=C3OC)=CNC12 Chemical compound CC1=CC=CC=C2C(/S=C(/C=CC=C3)\C=C3OC)=CNC12 KUMOSZCIHPSDAK-UHFFFAOYSA-N 0.000 description 1
- CHLICZRVGGXEOD-UHFFFAOYSA-N Cc(cc1)ccc1OC Chemical compound Cc(cc1)ccc1OC CHLICZRVGGXEOD-UHFFFAOYSA-N 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a kind of using disulfide as the catalysis oxidation synthetic method of 3 sulfydryl indole class compounds of sulphur source, using Benzazole compounds and disulfide as reaction substrate, using potassium iodide and sodium nitrite as catalyst, using acetic acid as auxiliary agent, using oxygen as oxidant, reaction substrate in organic solvent, reacts under conditions of normal pressure, 40~80 DEG C of temperature, obtains the 3 sulfydryl indole class compounds through separating treatment after reaction.Synthetic method of the present invention, it is easy to operate and safe, to clean oxygen as terminal oxidant, Environmental costs are greatly reduced, reaction condition is mild.
Description
Technical field
The present invention relates to a kind of using disulfide as the catalysis oxidation synthetic method of the 3- sulfydryl indole class compounds of sulphur source.
Background technology
3- sulfydryl indole class compounds have extraordinary bioactivity, have irreplaceable role in drug.Its
It is concerned in the notable therapeutic effect for the treatment of cancer, HIV, allergy, heart disease, bacterium infection etc..More than ten years in past close
Two kinds are can be mainly divided at the strategy of 3- sulfydryl indole class compounds, one is prepare 3- sulfydryl indole classes by cyclization
Compound；Another kind is to react synthesis 3- sulfydryl indole class compounds with the nucleopilic reagent of sulfur-bearing by Benzazole compounds.
It is main when the nucleopilic reagent using sulfur-bearing reacts synthesis 3- sulfydryl indole class compounds with Benzazole compounds
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；(7) thiosulfate.Most common of which and what is be easy to get is disulfide and mercaptan, but
The general foul smelling of mercaptan compound, effect on environment are very big.In addition, the nucleopilic reagent in sulfur-bearing reacts conjunction with Benzazole compounds
In reaction at 3- sulfydryl indole class compounds, transition-metal catalyst or the oxidant of stoichiometry are often used, very
The harsh reaction condition of comparison is also needed in the case of more, these leverage its application in actual production.
It is successfully used to Yin using iodine as catalyst, the catalytic oxidation system that dimethyl sulfoxide (DMSO) (DMSO) is oxidant
Diindyl class compound and disulfide are (Green Chem., 2012,14) in the reacting of Material synthesis 3- sulfydryl indole class compounds,
But dimethyl sulfide is generated when DMSO is used as oxidant, it is unfavorable to environmental protection.In recent years, the green of cleaning oxygen source is made with molecular oxygen
Color catalytic oxidation technologies are increasingly subject to the attention of people.Because molecular oxygen is the sustainable natural resources used, use cost is low,
Atom economy is high, and oxidation reaction by-products are only water, do not generate pollution.
Invention content
The object of the present invention is to provide one kind using Benzazole compounds and disulfide as raw material, by catalytic oxidation system
The method of standby 3- sulfydryl indole class compounds.
To achieve the above object, the present invention adopts the following technical scheme that：Using disulfide as the 3- sulfydryl indole classes of sulphur source
Close the catalysis oxidation synthetic method of object, it is characterised in that：Using Benzazole compounds and disulfide as reaction substrate, with potassium iodide and
Sodium nitrite is catalyst, using acetic acid as auxiliary agent, using oxygen as oxidant, reaction substrate in organic solvent, in normal pressure, temperature
It is reacted under conditions of 40~80 DEG C, obtains the 3- sulfydryl indole class compounds through separating treatment after reaction.
Shown in the structural formula such as formula (II) of the reaction substrate Benzazole compounds, the reaction substrate thiosulfate
Structural formula such as formula (III), shown in obtained product structure formula such as formula (I)；
In formula (I) or 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, I, nitro, cyano, ester group, C1~C4 alkyl
Or C1~C2 alkoxies, preferably R3For H, F, Cl, cyano, methyl or methoxy.
In formula (I) or formula (III), R4For C4~C12 alkyl, phenyl, substituted phenyl, heteroaryl perfume base, substituted heteroaryl
Perfume base, naphthalene, substituted naphthalene, benzyl or substituted benzyl.The heteroaryl perfume base can be that ring includes the hetero atoms such as N, O, S
Aromatic radical.Substituted phenyl, substituted heteroaryl perfume base, substituted naphthalene and the substituted benzyl refers to phenyl ring, heteroaryl
Fragrant ring, naphthalene nucleus and benzyl benzene ring hydrogen are substituted by one or more substituents, and the substituent group is each independently selected from following
One of：Halogen, the alkyl of C1~C4, the alkoxy of C1-C4, trifluoromethyl and nitro.It is preferred that R4For normal-butyl, phenyl, halogenated
Phenyl, alkyl-substituted phenyl, alkoxy substituted phenyl, benzyl or naphthalene.
In the present invention, the organic solvent is acetonitrile or ethyl alcohol.
In the present invention, the reaction substrate Benzazole compounds and disulfide, KI, NaNO2Substance amount ratio be 100：
40~60：15~25：8~20.
In the present invention, the acetic acid quality dosage is recommended as 4~20 times of reaction substrate.
In the present invention, the solvent quality dosage is recommended as 10~80 times of reaction substrate.
In the present invention, the reaction temperature is 40~80 DEG C.
In the present invention, the reaction time is 1~8h.
The method of usually reaction solution post-processing is：After reaction, it removes solvent under reduced pressure, it is molten that sodium thiosulfate is added
Liquid stirs, and is then extracted with dichloromethane, isolates organic layer, dichloromethane is removed under reduced pressure, then carry out column chromatography for separation, with second
Ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, collects the eluent containing target compound, solvent is evaporated off up to product
3- sulfydryl indole class compounds.
The synthetic method of the present invention is specifically recommended to be：In organic solvent, substrate Benzazole compounds and two are added
Thioether, potassium iodide (KI), sodium nitrite (NaNO2) and acetic acid (HOAc), under the conditions of atmospheric oxygen, react 1 at 40~80 DEG C~
8h removes solvent under reduced pressure, and hypo solution stirring is added, is then extracted with dichloromethane, isolates organic layer, and decompression is steamed
Except solvent, then column chromatography for separation is carried out, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, collects chemical combination containing target
Solvent is evaporated off up to product 3- sulfydryl indole class compounds in the eluent of object；Organic solvent used is acetonitrile or ethyl alcohol；React bottom
Object Benzazole compounds and thiosulfate, KI, NaNO2Substance amount ratio be 100：40~60：15~25：8~20；It is described
Acetic acid quality dosage is 4~20 times of reaction substrate；The solvent quality dosage is 10~80 times of reaction substrate.
Synthetic method of the present invention, easy to operate and safe, advantage essentially consists in：
A) to clean oxygen as terminal oxidant, Environmental costs are greatly reduced.
B) reaction condition is mild.
Specific implementation mode
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)~(15)：
Embodiment 1：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
In the glass tube of 15mL, two (the 3- methoxybenzenes of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
Base) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, with the closed bottleneck of rubber stopper
Afterwards, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C
In oil bath, lower reaction 2h is stirred.Hypo solution stirring is added in reaction solution, is then extracted, is isolated with dichloromethane
Organic layer removes solvent under reduced pressure, then carries out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent,
The eluent containing target compound is collected, solvent is evaporated off up to 3- meta-methoxy thiophenyl -1H- indoles, separation yield 83%.
Embodiment 2：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that reaction temperature is changed to 80 DEG C, 3- meta-methoxy thiophenyl -1H- indoles
Separation yield be 84%.
Embodiment 3：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that acetonitrile is changed to ethyl alcohol, point of 3- meta-methoxy thiophenyl -1H- indoles
It is 85% from yield.
Embodiment 4：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that NaNO2Dosage be changed to 0.2mmol, 3- meta-methoxies thiophenyl-
The separation yield of 1H- indoles is 82%.
Embodiment 5：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that the dosage of KI is changed to 0.25mmol, NaNO2Dosage be changed to
The separation yield of 0.08mmol, 3- meta-methoxy thiophenyl -1H- indoles is 79%.
Embodiment 6：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that the dosage of two (3- methoxyphenyls) disulfides is changed to 0.6mmol,
The dosage of KI is changed to 0.15mmol, and the separation yield of 3- meta-methoxy thiophenyl -1H- indoles is 79%.
Embodiment 7：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that the dosage of two (3- methoxyphenyls) disulfides is changed to 0.4mmol,
The separation yield of 3- meta-methoxy thiophenyl -1H- indoles is 70%.
Embodiment 8：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that reaction temperature is changed to 40 DEG C, the reaction time is changed to 4h, methoxy between 3-
The separation yield of base thiophenyl -1H- indoles is 65%.
Embodiment 9：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 1)
Reaction step is with embodiment 1, except that acetonitrile content is changed to 10mL, the dosage of HOAc is changed to 2mL, first between 3-
The separation yield of oxygroup thiophenyl -1H- indoles is 81%.
Embodiment 10：Preparations of the 3- to chlorophenylthio -1H- indoles (formula 2)
In the glass tube of 15mL, two (the 4- fluorophenyls) two of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
The NaNO of thioether, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted
Enter oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C of oil bath
In, stir lower reaction 2h.Hypo solution stirring is added in reaction solution, is then extracted, is isolated organic with dichloromethane
Layer, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, is collected
Solvent is evaporated off up to 3- to chlorophenylthio -1H- indoles, separation yield 88% in eluent containing target compound.
Embodiment 11：Preparations of the 3- to chlorophenylsulfanyl -1H- indoles (formula 3)
In the glass tube of 15mL, two (the 4- chlorphenyls) two of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
The NaNO of thioether, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted
Enter oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C of oil bath
In, stir lower reaction 2h.Hypo solution stirring is added in reaction solution, is then extracted, is isolated organic with dichloromethane
Layer, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, is collected
Solvent is evaporated off up to 3- to chlorophenylsulfanyl -1H- indoles, separation yield 87% in eluent containing target compound.
Embodiment 12：Preparations of the 3- to bromophenylthio -1H- indoles (formula 4)
In the glass tube of 15mL, two (the 4- bromophenyls) two of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
The NaNO of thioether, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted
Enter oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C of oil bath
In, stir lower reaction 2h.Hypo solution stirring is added in reaction solution, is then extracted, is isolated organic with dichloromethane
Layer, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, is collected
Solvent is evaporated off up to 3- to bromophenylthio -1H- indoles, separation yield 85% in eluent containing target compound.
Embodiment 13：The preparation of methylphenyl-sulfanyl -1H- indoles (formula 5) between 3-
In the glass tube of 15mL, two (the 3- aminomethyl phenyls) of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
The NaNO of disulfide, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper,
It is inserted into oxygen ball, then the HOAc of 1mL is added with syringe into reaction tube, reaction tube is put into and is previously heated to 60 DEG C of oil bath
In, stir lower reaction 2h.Hypo solution stirring is added in reaction solution, is then extracted, is isolated organic with dichloromethane
Layer, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, is collected
Solvent is evaporated off up to methylphenyl-sulfanyl -1H- indoles between 3-, separation yield 82% in eluent containing target compound.
Embodiment 14：The preparation of 3- meta-methoxy thiophenyl -1H- indoles (formula 6)
In the glass tube of 15mL, two (the 3- methoxybenzenes of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
Base) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, with the closed bottleneck of rubber stopper
Afterwards, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C
In oil bath, lower reaction 3h is stirred.Hypo solution stirring is added in reaction solution, is then extracted, is isolated with dichloromethane
Organic layer removes solvent under reduced pressure, then carries out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent,
The eluent containing target compound is collected, solvent is evaporated off up to 3- meta-methoxy thiophenyl -1H- indoles, separation yield 84%.
Embodiment 15：The preparation of 7- methyl -3- meta-methoxy thiophenyl -1H- indoles (formula 7)
In the glass tube of 15mL, two (the 3- first of the acetonitrile of 5mL, the 7- Methyl-1H-indoles of 1mmol, 0.5mmol are added
Phenyl) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, it is close with rubber stopper
After closing bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to
In 60 DEG C of oil bath, lower reaction 3h is stirred.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane,
Organic layer is isolated, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is to wash
De- agent, collects the eluent containing target compound, and solvent is evaporated off up to 7- methyl -3- Methoxv-phenylsulfanvl -1H- indoles, separation
Yield is 81%.
Embodiment 16：The preparation of 5- methoxyl group -3- meta-methoxy thiophenyl -1H- indoles (formula 8)
In the glass tube of 15mL, two (3- of the acetonitrile of 5mL, the 5- methoxyl group -1H- indoles of 1mmol, 0.5mmol are added
Methoxyphenyl) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, uses rubber stopper
After closed bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into advance heating
Into 60 DEG C of oil baths, lower reaction 3h is stirred.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane
It takes, isolates organic layer, remove solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor
For eluant, eluent, the eluent containing target compound is collected, solvent is evaporated off up to 5- methoxyl group -3- Methoxv-phenylsulfanvl -1H- Yin
Diindyl, separation yield 82%.
Embodiment 17：The preparation of the fluoro- 3- meta-methoxies thiophenyl -1H- indoles (formula 9) of 5-
In the glass tube of 15mL, the fluoro- 1H- indoles of 5- of acetonitrile, 1mmol that 5mL is added, two (the 3- methoxies of 0.5mmol
Base phenyl) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, it is closed with rubber stopper
After bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60
DEG C oil bath in, stir and lower react 3h.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane, point
Organic layer is separated out, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is elution
Agent collects the eluent containing target compound, solvent is evaporated off up to the fluoro- 3- Methoxv-phenylsulfanvls -1H- indoles of 5-, separation yield
It is 83%.
Embodiment 18：The preparation of the chloro- 3- meta-methoxies thiophenyl -1H- indoles (formula 10) of 5-
In the glass tube of 15mL, the chloro- 1H- indoles of 5- of acetonitrile, 1mmol that 5mL is added, two (the 3- methoxies of 0.5mmol
Base phenyl) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, it is closed with rubber stopper
After bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60
DEG C oil bath in, stir and lower react 3h.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane, point
Organic layer is separated out, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is elution
Agent collects the eluent containing target compound, solvent is evaporated off up to the chloro- 3- Methoxv-phenylsulfanvls -1H- indoles of 5-, separation yield
It is 75%.
Embodiment 19：Preparations of the 5- cyano -3- to Methoxv-phenylsulfanvl -1H- indoles (formula 11)
In the glass tube of 15mL, two (the 4- first of the acetonitrile of 5mL, the 5- cyano-1 H-indols of 1mmol, 0.5mmol are added
Phenyl) disulfide, the KI of 0.2mmol and 0.1mmol NaNO2, inner air tube is reacted with replacement of oxygen, it is close with rubber stopper
After closing bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to
In 60 DEG C of oil bath, lower reaction 5h is stirred.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane,
Organic layer is isolated, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is to wash
De- agent, collects the eluent containing target compound, and solvent is evaporated off up to 5- cyano -3- to Methoxv-phenylsulfanvl -1H- indoles, divides
It is 77% from yield.
Embodiment 20：Preparations of the 1- methyl -2- phenyl -3- to chlorophenylthio -1H- indoles (formula 12)
In the glass tube of 15mL, the acetonitrile of 5mL, the 1- methyl -2- phenyl -1H- indoles of 1mmol, 0.5mmol is added
The NaNO of two (4- fluorophenyls) disulfides, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, uses rubber
After filling in closed bottleneck, it is inserted into oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is added in advance
In the oil bath of heat to 60 DEG C, lower reaction 5h is stirred.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane
It takes, isolates organic layer, remove solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor
For eluant, eluent, the eluent containing target compound is collected, solvent is evaporated off up to 1- methyl -2- phenyl -3- to chlorophenylthio -1H-
Indoles, separation yield 83%.
Embodiment 21：Preparations of the 1- methyl -2- phenyl -3- to chlorophenylthio -1H- indoles (formula 12)
Reaction step is with embodiment 19, except that the dosage of acetonitrile is changed to 3mL, 1- methyl -2- phenyl -3- are to fluorobenzene
The separation yield of sulfenyl -1H- indoles is 79%.
Embodiment 22：The preparation of 3- (naphthalene -2- sulfenyls) -1H- indoles (formula 13)
In the glass tube of 15mL, two (naphthalene -2- bases) two of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol are added
The NaNO of thioether, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted
Enter oxygen ball, then the HOAc of 1mL is added into reaction tube with syringe, reaction tube is put into and is previously heated to 60 DEG C of oil bath
In, stir lower reaction 8h.Hypo solution stirring is added in reaction solution, is then extracted, is isolated organic with dichloromethane
Layer, removes solvent under reduced pressure, then carry out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, is collected
Solvent is evaporated off up to 3- (naphthalene -2- sulfenyls) -1H- indoles, separation yield 85% in eluent containing target compound.
Embodiment 23：The preparation of 3- benzyl -1H- indoles (formula 14)
In the glass tube of 15mL, be added the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol benzyldithio toluene,
The NaNO of the KI and 0.1mmol of 0.2mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted into oxygen
Balloon, then the HOAc of 1mL is added with syringe into reaction tube, reaction tube is put into and is previously heated in 60 DEG C of oil bath, is stirred
Mix lower reaction 5h.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane, isolates organic layer, subtracted
Solvent is evaporated off in pressure, then carries out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, collects and contains target
Solvent is evaporated off up to 3- benzyl -1H- indoles, separation yield 79% in the eluent of compound.
Embodiment 24：The preparation of 3- normal-butyl -1H- indoles (formula 15)
In the glass tube of 15mL, two sulphur of di-n-butyl of the acetonitrile of 5mL, the 1H- indoles of 1mmol, 0.5mmol is added
The NaNO of ether, the KI of 0.2mmol and 0.1mmol2, inner air tube is reacted with replacement of oxygen, after the closed bottleneck of rubber stopper, is inserted into
Oxygen ball, then the HOAc of 1mL is added with syringe into reaction tube, reaction tube is put into and is previously heated in 60 DEG C of oil bath,
Stirring is lower to react 4h.Hypo solution stirring is added in reaction solution, is then extracted with dichloromethane, isolates organic layer,
It removes solvent under reduced pressure, then carries out column chromatography for separation, with ether/petroleum ether volume ratio 1：5 mixed liquor is eluant, eluent, collects and contains mesh
The eluent for marking compound, is evaporated off solvent up to 3- normal-butyl -1H- indoles, separation yield 82%.
Claims (3)
1. using disulfide as the catalysis oxidation synthetic method of the 3- sulfydryl indole class compounds of sulphur source, which is characterized in that with indoles
Class compound and disulfide are reaction substrate, using potassium iodide and sodium nitrite as catalyst, using acetic acid as auxiliary agent, using oxygen as oxygen
Agent, reaction substrate in organic solvent, react under conditions of normal pressure, 40~80 DEG C of temperature, after reaction through separation at
Reason obtains the 3- sulfydryl indole class compounds；
Shown in the structural formula such as formula (II) of the reaction substrate Benzazole compounds, the structure of the reaction substrate thiosulfate
Formula such as formula (III), shown in obtained product structure formula such as formula (I)：
In formula (I) or formula (II), R1For H or C1~C4 alkyl, preferably R1For H or methyl；R2For H, C1~C4 alkyl, phenyl or
Substituted-phenyl, preferably R2For H, methyl or phenyl；R3For for H, F, Cl, Br, I, nitro, cyano, ester group, C1~C4 alkyl or C1
~C2 alkoxies, preferably R3For H, F, Cl, cyano, methyl or methoxy；
In formula (I) or formula (III), R4For C4~C12 alkyl, phenyl, substituted phenyl, heteroaryl perfume base, substituted heteroaryl perfume base,
Naphthalene, substituted naphthalene, benzyl or substituted benzyl；The heteroaryl perfume base can be that ring includes the heteroatomic virtue such as N, O, S
Perfume base；Substituted phenyl, substituted heteroaryl perfume base, substituted naphthalene and the substituted benzyl refer to phenyl ring, miscellaneous aromatic rings,
Naphthalene nucleus and benzyl benzene ring hydrogen are substituted by one or more substituents, and the substituent group is each independently selected from one of following：
Halogen, the alkyl of C1~C4, the alkoxy of C1-C4, trifluoromethyl and nitro；It is preferred that R4For normal-butyl, phenyl, halogenophenyl,
Alkyl-substituted phenyl, alkoxy substituted phenyl, benzyl or naphthalene.
2. the method as described in claim 1, it is characterised in that：The organic solvent is acetonitrile or ethyl alcohol.
3. the method as described in claim 1, it is characterised in that：The reaction substrate Benzazole compounds and disulfide, KI,
NaNO2Substance amount ratio be 100：40~60：15~25：8~20.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810343486.7A CN108440375B (en) | 2018-04-17 | 2018-04-17 | Catalytic oxidation synthesis method of 3-mercaptoindole compound with disulfide as sulfur source |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810343486.7A CN108440375B (en) | 2018-04-17 | 2018-04-17 | Catalytic oxidation synthesis method of 3-mercaptoindole compound with disulfide as sulfur source |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108440375A true CN108440375A (en) | 2018-08-24 |
| CN108440375B CN108440375B (en) | 2021-01-29 |
Family
ID=63200107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810343486.7A Active CN108440375B (en) | 2018-04-17 | 2018-04-17 | Catalytic oxidation synthesis method of 3-mercaptoindole compound with disulfide as sulfur source |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108440375B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232525A (en) * | 2018-09-27 | 2019-01-18 | 浙江工业大学 | A kind of photochemical catalytic oxidation synthetic method of thioxanthones compound |
| CN111303117A (en) * | 2020-03-13 | 2020-06-19 | 常州工程职业技术学院 | Preparation method of nitrogen heterocyclic ring substituted indole thioether compound |
| CN111848488A (en) * | 2020-06-19 | 2020-10-30 | 温州医科大学 | Method for synthesizing 3-selenoindole derivative |
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 |
| CN103641767A (en) * | 2013-11-22 | 2014-03-19 | 沈阳药科大学 | Substituted phenylindolyl selenide, selenoxide, selenone and application as tumor cell proliferation inhibitor |
-
2018
- 2018-04-17 CN CN201810343486.7A patent/CN108440375B/en active Active
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 |
| CN103641767A (en) * | 2013-11-22 | 2014-03-19 | 沈阳药科大学 | Substituted phenylindolyl selenide, selenoxide, selenone and application as tumor cell proliferation inhibitor |
Non-Patent Citations (1)
| Title |
|---|
| XIAOXIA LIU ET AL.: "Iodine-catalyzed Direct Thiolation of Indoles with Thiols Leading to 3-Thioindoles Using Air as the Oxidant", 《CATALYSIS LETTERS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232525A (en) * | 2018-09-27 | 2019-01-18 | 浙江工业大学 | A kind of photochemical catalytic oxidation synthetic method of thioxanthones compound |
| CN111303117A (en) * | 2020-03-13 | 2020-06-19 | 常州工程职业技术学院 | Preparation method of nitrogen heterocyclic ring substituted indole thioether compound |
| CN111848488A (en) * | 2020-06-19 | 2020-10-30 | 温州医科大学 | Method for synthesizing 3-selenoindole derivative |
| CN111848488B (en) * | 2020-06-19 | 2022-12-27 | 温州医科大学 | Method for synthesizing 3-selenoindole derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108440375B (en) | 2021-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104803898B (en) | Aryl-alkyl and aryl-aryl thioether compound and synthesis method thereof | |
| CN106928117B (en) | A kind of preparation method of deuterated aromatics organic compound | |
| CN108440375A (en) | Using disulfide as the catalysis oxidation synthetic method of the 3- sulfydryl indole class compounds of sulphur source | |
| CN107620088B (en) | A kind of method of electrochemical catalytic oxidation synthesis 3- sulfydryl indole class compound | |
| CN109320496B (en) | Selenocyanization reagent and preparation method and application thereof | |
| CN107056727A (en) | A kind of oxadiazole compound of 5 arylseleno of 2 aryl 1,3,4 and preparation method | |
| CN110386885B (en) | Preparation method of visible light promoted beta-carbonyl sulfone compound | |
| CN108586310A (en) | The catalysis oxidation synthetic method of 3- sulfydryl indole class compounds | |
| Dillon et al. | Synthesis of 2-substituted benzo [b] thiophenes via gold (i)–NHC-catalyzed cyclization of 2-alkynyl thioanisoles | |
| CN108530354A (en) | A kind of synthetic method of the compound of class containing phenylsulfonylquinoline | |
| CN107266414A (en) | A kind of synthetic method of aminomethyl thiophenes | |
| Uchiro et al. | Non-aqueous reduction of aromatic sulfonyl chlorides to thiols using a dichlorodimethylsilane-zinc-dimethylacetamide system | |
| CN105218540B (en) | A kind of preparation method of 3 thiocarbamoyl imidazoles of C simultaneously [1,2 a] pyridine compounds and their | |
| CN104557957B (en) | Synthetic method of spiro-oxoindole ethylene oxide derivative | |
| CN108129478A (en) | A kind of copper catalysis synthetic method of organic sulphones and application | |
| CN109810030B (en) | Preparation method of visible light-promoted asymmetric sulfoxide compound | |
| Nowak et al. | Synthesis of novel heteropentacenes containing nitrogen, sulfur and oxygen or selenium | |
| Ebdrup | Preparation of 3-substituted 10-methylphenothiazines | |
| CN105418481B (en) | A kind of preparation method of 3 indoles thioether | |
| CN108484518A (en) | A kind of 2-（2,4,6- trimethylbenzene selenos）- 5- methylbenzoxazoles compound and preparation method | |
| CN105693778B (en) | The method of N- methoxymethylamide guiding synthesis ferrocene and Pyridione derivatives | |
| CN109485594B (en) | Synthetic method of 3-alkynyl pyrrole compound | |
| CN107311958B (en) | A kind of synthetic method of benzothiazole-nitrogen-containing heterocycle hybrid | |
| CN109369497B (en) | Synthesis method of N-pyrrolylpiperidine compound | |
| CN106467481B (en) | The synthetic method of indoles -3- aryl ketone derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |