CN106432132A - Preparation method of 2-arylbenzothiazole compound - Google Patents
Preparation method of 2-arylbenzothiazole compound Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- C07D277/66—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2 with aromatic rings or ring systems directly attached in position 2
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Abstract
The invention relates to a preparation method of a 2-arylbenzothiazole compound. The method comprises the steps that a benzothiazole compound, diaryliodonium salt, a catalyst, a phosphine ligand and alkali are added into an organic solvent, reacting is conducted for 20-36 hours at the temperature of 60 DEG C to 100 DEG C, and after complete reacting is achieved, reaction liquid is obtained; after the reaction liquid is sequentially subjected to conventional extraction, drying, concentration and column chromatography separation, the compound is obtained. The preparation method belongs to a two-component one-pot reaction, the conditions are mild, the raw materials are easy to prepare and obtain, operation is easy, the yield is high, green environmental protection and economic conservation are achieved, large-scale production can be achieved, and the good application potential on medicine, pesticides, organic synthesis and materials and the good industrial application prospect are achieved.
Description
Technical field
The present invention relates to aryl compound substitution heterocycle class in synthetic organic chemical art, more particularly to a kind of 2- aryl benzene
And the preparation method of thiazole compound.
Background technology
Aryl benzothiazole compound is the important organic synthesiss of a class and medical synthetic intermediate, effectively can use
In the synthesis fragment for building anticancer class medicine, antitumor class medicine and HCV-Ab IgG virus type drug molecule, especially anti-in non-steroidal
Scorching class medicine（COX-2 II type epoxidase）Synthesis on application more cause synthesis chemist extensive concern.
Nineteen fifty-seven, aminothiophenol is mixed by Hein seminar first with benzoic acid, adds the polyphosphoric acids of q.s to enter
Row stirs to obtain pastel, is to slowly warm up to 250 DEG C and continues stirring 4 hours at such a temperature, locates after carrying out reactant liquor afterwards
Reason obtains 2- phenylbenzothiazol class compound, but its reaction condition is more harsh, and post-processing operation is relative complex（（Americanized
Association's will）J. Am. Chem. Soc. 1957, 79, 427.）.1964, Collings etc. was with N, S diacyl neighbour's amino
Phenylmercaptan. is converted into 2- phenylbenzothiazol for raw material high yield.Various countries' research group is in 2- aryl benzothiazoles in recent years
Achieve larger progress in terms of the study on the synthesis of compound, outstanding behaviours be with raw material simple and easy to get, the urging of cheap green
What the synthesis path of change system and easy strong operability carried out high yield obtains target product.Such as：Thanh seminar in 2014
With halogenated nitrobenzene, benzylamine and elemental sulfur as raw material, pyridine is simultaneously introduced, reacts 16 hours at 100 DEG C, with medium to higher
Yield obtain 2- phenylbenzothiazol（（Germany should change）Angew. Chem. 2014, 126, 14028-14032.）.2015
Year, Yang-Jie Wu seminar was simultaneously introduced nitre with adjacent mercaptoaniline with benzyl chloride as raw material with bivalence Schweinfurt green as catalyst
The additive such as sour potassium, potassium bicarbonate and Benzene Chloride, reaction at 140 DEG C obtains 2- phenyl benzo thiophene with 60% yield in 20 hours
Azoles（（Tetrahedron）Tetrahedron. 2015, 71, 57-63.）.Song-Lin Zhang seminar is with benzo within 2015
Thiazole and phenylboric acid are raw material, with trivalent iron salt and cupric salt as catalyst, to be simultaneously introduced tert-butyl alcohol lithium, di-t-butyl peroxide
Compound and 1,10- Phen etc. are additive, reacted 12 hours as solvent with toluene, obtained with 80% yield at 110 DEG C
To 2- phenylbenzothiazol class compound（（Synthesis）Synthesis. 2015, 47, 42-48.）.The same year Chikate,
R.C. seminar employs new photocatalyst with benzaldehyde and adjacent mercaptoaniline as raw material（Cadmium selenide (CdSe)/illiteracy takes off
Native (MMT) nanoparticle）Under the low light level, react 0.5 hour, finally target product has been obtained with 94% yield.But the method
Have the disadvantage that the preparation of catalyst is more complicated with sign（（Green Chemistry）Green. Chem. 2015, 17, 3879-
3888.）.From the point of view of known document, so far there is not yet being disclosed about using benzothiazole compound and Diaryl iodonium
The method that salt synthesizes 2- aryl benzothiazole compound as reaction raw materials high yield.
Content of the invention
The technical problem to be solved is to provide a kind of inexpensive, efficient, quick 2- aryl benzothiazole
The preparation method of class compound.
For solving the above problems, a kind of preparation method of 2- aryl benzothiazole compound of the present invention, which is special
Levy and be：The method is referred to successively will be organic for the addition of benzothiazole compound, diaryl group iodized salt, catalyst, Phosphine ligands and alkali
In solvent, react 20 ~ 36 hours at 60 ~ 100 DEG C, after reaction completely, obtain reactant liquor；The reactant liquor is successively through conventional extraction, dry
Obtain final product after dry, concentration, column chromatography for separation；Wherein：The catalyst is 1 with the mol ratio of the benzothiazole compound：50~
100；The benzothiazole compound is 1 with the mol ratio of the diaryl group iodized salt：1.5~3.0；The benzothiazoles
Compound is 1 with the mol ratio of the Phosphine ligands：50~100；The benzothiazole compound is 1 with the mol ratio of the alkali：
1.5~3.0；The benzothiazole compound is 1 with the mol ratio of the reaction dissolvent：150~360.
The benzothiazole compound is benzothiazole, 4- methylbenzothiazole, 5- bromo benzothiazole, 6- methyl benzo
Thiazole, 6- bromo benzothiazole, 6- chloro benzothiazole, 6- methoxybenzothiazole, 6- ethoxyl benzo thiazole, 4,6- dimethyl benzene
And any one in thiazole, 7- nitrobenzene thiazole.
The diaryl group iodized salt is diphenyl tetrafluoride boron iodine salt, 2- fluorophenyl（Phenyl）Tetrafluoride boron iodine salt, 2- toluene
Base（Phenyl）Tetrafluoride boron iodine salt, 4- nitrobenzophenone（Phenyl）Tetrafluoride boron iodine salt, 2- tolyl（4- tolyl）Tetrafluoride boron
Iodine salt, two（2- fluorophenyl）Tetrafluoride boron iodine salt, two（4- bromophenyl）In tetrafluoride boron iodine salt, diphenylsulfonium methanesulfonic acid iodine salt
Any one.
The catalyst refer to palladium, Palladous chloride., palladium bromide, palladium iodide, palladium trifluoroacetate, two（Acetylacetone,2,4-pentanedione）Palladium
A kind of.
The Phosphine ligands refer to that triphenylphosphine, 1,2- are double（Diphenylphosphine）Ethane, 1,1 ＇-bis-（Diphenylphosphine）Ferrocene,
1,3- is double（Diphenylphosphine）Any one in propane, tricyclohexyl phosphine, tri-o-tolyl phosphine.
The alkali is referred in potassium carbonate, potassium phosphate, potassium tert-butoxide, tetrabutylammonium acetate ammonium, cesium carbonate, triethylamine, pyridine
A kind of.
The solvent refers to N,N-dimethylformamide, 1,2- dichloroethanes, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, first
One kind in benzene, dimethylbenzene, dioxane.
The present invention has advantages below compared with prior art：
1st, the present invention is using diaryl group iodized salt as aromatic yl reagent-ing, and using bi-component one pot reaction, reaction condition is gentle, efficiency
High.
2nd, catalyst of the present invention using common palladium compound as reaction, with the use of phosphine compound, without system
Standby transition metal complex, it is not necessary to which anhydrous and oxygen-free is operated, operation is simple, product yield high；And whole substrate spectrum is relatively
Prior art report more extensive.
3rd, the inventive method environmental protection, the by-product aryl iodide use value height of generation, recyclable recycling, can
Effectively reduce production cost, accomplish scale production, in terms of medicine, pesticide, organic synthesiss and material, have good application
Potentiality, with preferable prospects for commercial application.
Specific embodiment
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 1, the method is referred to successively by benzo thiophene
Azoles, diphenyl tetrafluoride boron iodine salt, palladium, 1,3- are double（Diphenylphosphine）Propane and cesium carbonate add N,N-dimethylformamide
In, react 24 hours at 80 DEG C.
Wherein：Palladium is 1 with the mol ratio of benzothiazole：60；Benzothiazole is rubbed with diphenyl tetrafluoride boron iodine salt
You are than being 1：3.0；Benzothiazole is double with 1,3-（Diphenylphosphine）The mol ratio of propane is 1：60；Benzothiazole is rubbed with cesium carbonate
You are than being 1：3.0；Benzothiazole is 1 with the mol ratio of N,N-dimethylformamide：150.
Whole course of reaction is tracked with thin layer chromatography, i.e., sampled every 1 hour, dripped respectively with capillary tube on silica gel plate
Enter to react liquid spotting, material liquid benzothiazole and diphenyl tetrafluoride boron iodine salt point sample, at three point samples on the same line, so
Afterwards silica gel plate being put into volume ratio is filled for 10：1：In the exhibition bottle of 1 petroleum ether, ethyl acetate and dichloromethane mixed liquor.Walk
After the completion of plate, then silica gel plate is placed under uviol lamp or is observed in iodine flask, if do not had and material liquid benzothiazole in reactant liquor
The point for flushing, then show that reaction is complete, now obtains reactant liquor.
Reactant liquor is extracted three times respectively with the ethyl acetate with reaction dissolvent amount equivalent, is merged organic faciess, is obtained extract.
Anhydrous magnesium sulfate is added and is dried in extract, obtain filtrate after filtering；Then Shanghai Asia Rong Shenghua is adopted
The RE-52AA type Rotary Evaporators of company limited's production carry out removing solvent under reduced pressure at 40 DEG C, obtain concentrated solution；Again in concentrated solution
Add the silica gel of 2 ~ 3 times of concentrated solution quality to carry out sample is mixed, sample will be mixed and be put in chromatographic column, it is 10 to add volume ratio：1：1 oil
Ether-ethyl acetate-dichloromethane mixed liquor carries out eluting and separates, and finally collects eluent, eluent is put into Rotary Evaporators
In, 2- phenylbenzothiazol is obtained final product after being concentrated at 40 DEG C, yield is 92%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 2, the method is referred to successively by benzo thiophene
Azoles, two（2- fluorophenyl）Tetrafluoride boron iodine salt, Palladous chloride., 1,3- are double（Diphenylphosphine）Propane and tetrabutylammonium acetate ammonium add N, N-
In dimethylformamide, react 25 hours at 70 DEG C.
Wherein：Palladous chloride. is 1 with the mol ratio of benzothiazole：60, benzothiazole and two（2- fluorophenyl）Tetrafluoride boron iodine
The mol ratio of salt is 1：3, benzothiazole and 1,3- are double（Diphenylphosphine）The mol ratio of propane is 1：60, benzothiazole and the tetrabutyl
The mol ratio of ammonium acetate is 1：3, benzothiazole is 1 with the mol ratio of DMF：160.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- (2- fluorophenyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is 85%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 3, the method is referred to successively by raw material benzo
Thiazole, two（4- bromophenyl）Tetrafluoride boron iodine salt, palladium, triphenylphosphine and potassium carbonate are put in reaction dissolvent acetonitrile, 80
React 20 hours at DEG C.
Wherein：Palladium is 1 with the mol ratio of benzothiazole：65, benzothiazole and two（4- bromophenyl）Tetrafluoride boron iodine
The mol ratio of salt is 1：2.5, benzothiazole is 1 with the mol ratio of triphenylphosphine：65, benzothiazole with the mol ratio of potassium carbonate is
1：2.5, benzothiazole is 1 with the mol ratio of acetonitrile：175.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- (4- bromophenyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is 88%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 4, the method is referred to successively by raw material benzo
Thiazole, 2- tolyl（Phenyl）Tetrafluoride boron iodine salt, palladium bromide, triphenylphosphine and potassium phosphate are put in reaction dissolvent acetonitrile,
React 36 hours at 60 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of benzothiazole：50, benzothiazole and 2- tolyl（Phenyl）Tetrafluoride boron
The mol ratio of iodine salt is 1：2.5, benzothiazole is 1 with the mol ratio of triphenylphosphine：50, the mol ratio of benzothiazole and potassium phosphate
For 1：2.5, benzothiazole is 1 with the mol ratio of acetonitrile：150.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- (2- tolyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is 80%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 5, the method is referred to successively by raw material benzo
Thiazole, 4- nitrobenzophenone（Phenyl）Tetrafluoride boron iodine salt, palladium iodide, tricyclohexyl phosphine and potassium tert-butoxide are put into reaction dissolvent 1,2-
In dichloroethanes, react 24 hours at 80 DEG C.
Wherein：Palladium iodide is 1 with the mol ratio of benzothiazole：85, benzothiazole and 4- nitrobenzophenone（Phenyl）Tetrafluoride
The mol ratio of boron iodine salt is 1：2.5, benzothiazole is 1 with the mol ratio of tricyclohexyl phosphine：85, benzothiazole and potassium tert-butoxide
Mol ratio is 1：2.5, the mol ratio of benzothiazole and 1,2- dichloroethanes is 1：175.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- (4- nitrobenzophenone) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is 88%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 6, the method is referred to successively by raw material benzo
Thiazole, 2- tolyl（4- tolyl）Tetrafluoride boron iodine salt, palladium trifluoroacetate, 1,2- are double（Diphenylphosphine）Ethane and triethylamine are put
Enter in reaction dissolvent toluene, react 24 hours at 90 DEG C.
Wherein：Palladium trifluoroacetate is 1 with the mol ratio of benzothiazole：95, benzothiazole and 2- tolyl（4- tolyl）
The mol ratio of tetrafluoride boron iodine salt is 1：2.0, benzothiazole and 1,2- are double（Diphenylphosphine）The mol ratio of ethane is 1：95, benzo
Thiazole is 1 with the mol ratio of triethylamine：2.0, benzothiazole is 1 with the mol ratio of toluene：200.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- (2- tolyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is 75%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 7, the method is referred to successively by raw material benzo
Thiazole, diphenylsulfonium methanesulfonic acid iodine salt, two（Acetylacetone,2,4-pentanedione）Palladium, tri-o-tolyl phosphine and cesium carbonate are put into reaction dissolvent diformazan
In base sulfoxide, react 30 hours at 85 DEG C.
Wherein：Two（Acetylacetone,2,4-pentanedione）Palladium is 1 with the mol ratio of benzothiazole：50, benzothiazole and diphenylsulfonium first sulphur
The mol ratio of sour iodine salt is 1：2.0, benzothiazole is 1 with the mol ratio of tri-o-tolyl phosphine：50, benzothiazole and cesium carbonate
Mol ratio is 1：2.0, benzothiazole is 1 with the mol ratio of dimethyl sulfoxide：200.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 2- phenylbenzothiazol successively after extraction, dry, concentration, column chromatography for separation, and yield is 72%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 8, the method is referred to successively by raw material 4- first
Base benzothiazole, diphenyl tetrafluoride boron iodine salt, palladium bromide, tri-o-tolyl phosphine and cesium carbonate are put into reaction dissolvent tetrahydrofuran
In, react 30 hours at 90 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of 4- methylbenzothiazole：100,4- methylbenzothiazoles and diphenyl tetrafluoro
The mol ratio for changing boron iodine salt is 1：2.0,4- methylbenzothiazoles are 1 with the mol ratio of tri-o-tolyl phosphine：100,4- methylbenzene
And thiazole is 1 with the mol ratio of cesium carbonate：2.0,4- methylbenzothiazoles are 1 with the mol ratio of tetrahydrofuran：178.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 4- methyl -2- phenylbenzothiazol successively after extraction, dry, concentration, column chromatography for separation, and yield is 73%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 9, the method is referred to successively by raw material 5- bromine
Benzothiazole, diphenyl tetrafluoride boron iodine salt, palladium, tricyclohexyl phosphine and potassium phosphate are put in reaction dissolvent dimethylbenzene,
React 28 hours at 85 DEG C.
Wherein：Palladium is 1 with the mol ratio of 5- bromo benzothiazole：90,5- bromo benzothiazoles and diphenyl tetrafluoride boron
The mol ratio of iodine salt is 1：2.5,5- bromo benzothiazoles are 1 with tricyclohexyl phosphine mol ratio：90,5- bromo benzothiazoles and potassium phosphate
Mol ratio be 1：2.5,5- bromo benzothiazoles are 1 with the mol ratio of dimethylbenzene：150.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product the bromo- 2- phenylbenzothiazol of 5- successively after extraction, dry, concentration, column chromatography for separation, and yield is 80%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 10, the method is referred to successively by raw material 6-
Methoxybenzothiazole, diphenyl tetrafluoride boron iodine salt, Palladous chloride., 1,1 ＇-bis-（Diphenylphosphine）Ferrocene and pyridine are put into instead
Answer in solvent toluene, react 30 hours at 95 DEG C.
Wherein：Palladous chloride. is 1 with the mol ratio of 6- methoxybenzothiazole：75,6- methoxybenzothiazoles and diphenyl
The mol ratio of tetrafluoride boron iodine salt is 1：2.3,6- methoxybenzothiazoles and 1,1 ＇-bis-（Diphenylphosphine）Ferrocene mol ratio is
1：75,6- methoxybenzothiazoles are 1 with the mol ratio of potassium phosphate：2.3,6- methoxybenzothiazoles with the mol ratio of toluene are
1：150.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 6- methoxyl group -2- phenylbenzothiazol successively after extraction, dry, concentration, column chromatography for separation, and yield is 78%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 11, the method is referred to successively by raw material 6-
Bromo benzothiazole, diphenyl tetrafluoride boron iodine salt, palladium iodide, triphenylphosphine and tetrabutylammonium acetate ammonium are put into reaction dissolvent 1,2- bis-
In ethyl chloride, react 30 hours at 65 DEG C.
Wherein：Palladium iodide is 1 with the mol ratio of 6- bromo benzothiazole：90,6- bromo benzothiazoles and diphenyl tetrafluoride boron
The mol ratio of iodine salt is 1：1.5,6- bromo benzothiazoles are 1 with triphenylphosphine mol ratio：90,6- bromo benzothiazoles and tetrabutyl vinegar
The mol ratio of sour ammonium is 1：The mol ratio of 1.5,6- bromo benzothiazoles and 1,2- dichloroethanes is 1：250.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product the bromo- 2- phenylbenzothiazol of 6- successively after extraction, dry, concentration, column chromatography for separation, and yield is 85%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 12, the method is referred to successively by raw material 7-
Nitrobenzene thiazole, diphenyl tetrafluoride boron iodine salt, palladium bromide, tricyclohexyl phosphine and potassium carbonate are put into reaction dissolvent dioxane
In, react 36 hours at 95 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of 7- nitrobenzene thiazole：50,7- nitrobenzene thiazoles and diphenyl tetrafluoro
The mol ratio for changing boron iodine salt is 1：1.8,7- nitrobenzene thiazoles are 1 with tricyclohexyl phosphine mol ratio：50,7- nitrobenzene thiazoles
Mol ratio with potassium carbonate is 1：1.8,7- nitrobenzene thiazoles are 1 with the mol ratio of dioxane：190.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 7- nitro -2- phenylbenzothiazol successively after extraction, dry, concentration, column chromatography for separation, and yield is 78%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 13, the method is referred to successively by raw material 4,
6- dimethyl-benzothiazole, diphenyl tetrafluoride boron iodine salt, Palladous chloride., 1,3- are double（Diphenylphosphine）Propane and cesium carbonate are put into instead
Answer in solvent acetonitrile, react 28 hours at 85 DEG C.
Wherein：Palladous chloride. is 1 with the mol ratio of 4,6- dimethyl-benzothiazole：80,4,6- dimethyl-benzothiazoles and two
The mol ratio of phenyl tetrafluoride boron iodine salt is 1：2.0,4,6- dimethyl-benzothiazoles and 1,3- are double（Diphenylphosphine）Propane mole
Than for 1：80,4,6- dimethyl-benzothiazoles are 1 with the mol ratio of cesium carbonate：2.0,4,6- dimethyl-benzothiazoles and acetonitrile
Mol ratio is 1：300.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 4,6- dimethyl -2- phenylbenzothiazol successively after extraction, dry, concentration, column chromatography for separation, and yield is
77%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 14, the method is referred to successively by raw material 6-
Methylbenzothiazole, two（4- bromophenyl）Tetrafluoride boron iodine salt, palladium bromide, 1,3- are double（Diphenylphosphine）Propane and potassium phosphate are put into
In reaction dissolvent DMF, react 30 hours at 75 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of 6- methylbenzothiazole：80,6- methylbenzothiazoles and two（4- bromobenzene
Base）The mol ratio of tetrafluoride boron iodine salt is 1：2.0,6- methylbenzothiazoles and 1,3- are double（Diphenylphosphine）Propane mol ratio is 1：
80,6- methylbenzothiazoles are 1 with the mol ratio of potassium phosphate：2.0,6- methylbenzothiazoles are rubbed with DMF
You are than being 1：280.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 6- methyl -2- (4- bromophenyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is
80%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 15, the method is referred to successively by raw material 6-
Ethoxyl benzo thiazole, two（2- fluorophenyl）It is molten that tetrafluoride boron iodine salt, palladium, tri-o-tolyl phosphine and potassium carbonate are put into reaction
In agent toluene, react 36 hours at 100 DEG C.
Wherein：Palladium is 1 with the mol ratio of 6- ethoxyl benzo thiazole：78,6- ethoxyl benzo thiazoles and two（2- fluorine
Phenyl）The mol ratio of tetrafluoride boron iodine salt is 1：3.0,6- ethoxyl benzo thiazoles are 1 with tri-o-tolyl phosphine mol ratio：78,
6- ethoxyl benzo thiazole is 1 with the mol ratio of potassium carbonate：3.0,6- ethoxyl benzo thiazoles are 1 with the mol ratio of toluene：
350.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 6- ethyoxyl -2- (2- fluorophenyl) benzothiazole, yield successively after extraction, dry, concentration, column chromatography for separation
For 78%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 16, the method is referred to successively by raw material 4-
Methylbenzothiazole, two（2- fluorophenyl）Tetrafluoride boron iodine salt, Palladous chloride., 1,1 ＇-bis-（Diphenylphosphine）Ferrocene and the tert-butyl alcohol
Potassium is put in reaction dissolvent dimethylbenzene, is reacted 22 hours at 100 DEG C.
Wherein：Palladous chloride. is 1 with the mol ratio of 4- methylbenzothiazole：98,4- methylbenzothiazoles and two（2- fluorobenzene
Base）The mol ratio of tetrafluoride boron iodine salt is 1：1.6,4- methylbenzothiazoles and 1,1 ＇-bis-（Diphenylphosphine）Ferrocene mol ratio
For 1：98,4- methylbenzothiazoles are 1 with the mol ratio of potassium tert-butoxide：The mol ratio of 1.6,4- methylbenzothiazoles and dimethylbenzene
For 1：230.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 4- methyl -2- (2- fluorophenyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is
72%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 17, the method is referred to successively by raw material 7-
Nitrobenzene thiazole, 2- tolyl（Phenyl）Tetrafluoride boron iodine salt, two（Acetylacetone,2,4-pentanedione）Palladium, tri-o-tolyl phosphorus and triethylamine are put
Enter in reaction dissolvent dimethyl sulfoxide, react 30 hours at 90 DEG C.
Wherein：Two（Acetylacetone,2,4-pentanedione）Palladium is 1 with the mol ratio of 7- nitrobenzene thiazole：85,7- nitrobenzene thiazoles and 2-
Tolyl（Phenyl）The mol ratio of tetrafluoride boron iodine salt is 1：2.3,7- nitrobenzene thiazoles with tri-o-tolyl phosphine mol ratio are
1：85,7- nitrobenzene thiazoles are 1 with the mol ratio of triethylamine：The mol ratio of 2.3,7- nitrobenzene thiazoles and dimethyl sulfoxide
For 1：200.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product 7- nitro -2- (2- tolyl) benzothiazole successively after extraction, dry, concentration, column chromatography for separation, and yield is
82%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 18, the method is referred to successively by raw material 4,
6- dimethyl-benzothiazole, two（4- bromophenyl）Tetrafluoride boron iodine salt, Palladous chloride., 1,3- are double（Diphenylphosphine）Propane and cesium carbonate
It is put in reaction dissolvent acetonitrile, reacts 36 hours at 85 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of 4,6- dimethyl-benzothiazole：100,4,6- dimethyl-benzothiazoles and two
（4- bromophenyl）The mol ratio of tetrafluoride boron iodine salt is 1：2.5,4,6- dimethyl-benzothiazoles and 1,3- are double（Diphenylphosphine）Third
Alkane mol ratio is 1：100,4,6- dimethyl-benzothiazoles are 1 with the mol ratio of cesium carbonate：2.5,4,6- dimethyl-benzothiazoles
Mol ratio with acetonitrile is 1：300.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method is obtained final product 4,6- dimethyl -2- (4- bromophenyl) benzothiazole, produces successively after extraction, dry, concentration, column chromatography for separation
Rate is 85%.
A kind of preparation method of 2- aryl benzothiazole compound of embodiment 19, the method is referred to successively by raw material 6-
Chloro benzothiazole, 2- fluorophenyl（Phenyl）Tetrafluoride boron iodine salt, Palladous chloride., 1,3- are double（Diphenylphosphine）Propane and cesium carbonate are put into
In reaction dissolvent acetonitrile, react 36 hours at 85 DEG C.
Wherein：Palladium bromide is 1 with the mol ratio of 6- chloro benzothiazole：100,6- chloro benzothiazoles and 2- fluorophenyl（Phenyl）
The mol ratio of tetrafluoride boron iodine salt is 1：2.5,6- chloro benzothiazoles and 1,3- are double（Diphenylphosphine）Propane mol ratio is 1：100,
6- chloro benzothiazole is 1 with the mol ratio of cesium carbonate：2.5,6- chloro benzothiazoles are 1 with the mol ratio of acetonitrile：360.
Whole course of reaction thin layer chromatography as described in embodiment 1 tracks to obtain reactant liquor；The reactant liquor is as described in embodiment 1
Method obtains final product the chloro- 2- of 6- successively after extraction, dry, concentration, column chromatography for separation（2- fluorophenyl）Benzothiazole, yield is
75%.
Claims (7)
1. a kind of preparation method of 2- aryl benzothiazole compound, it is characterised in that：The method is referred to successively by benzo thiophene
Azole compounds, diaryl group iodized salt, catalyst, Phosphine ligands and alkali are added in organic solvent, and at 60 ~ 100 DEG C, reaction 20 ~ 36 is little
When, reactant liquor is obtained after reaction completely；The reactant liquor is obtained final product successively after conventional extraction, drying, concentration, column chromatography for separation；Wherein：
The catalyst is 1 with the mol ratio of the benzothiazole compound：50~100；The benzothiazole compound with described
The mol ratio of diaryl group iodized salt is 1：1.5~3.0；The benzothiazole compound is 1 with the mol ratio of the Phosphine ligands：50~
100；The benzothiazole compound is 1 with the mol ratio of the alkali：1.5~3.0；The benzothiazole compound and institute
The mol ratio for stating reaction dissolvent is 1：150~360.
2. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：The benzene
And thiazole compound is for benzothiazole, 4- methylbenzothiazole, 5- bromo benzothiazole, 6- methylbenzothiazole, 6- bromobenzene simultaneously
Thiazole, 6- chloro benzothiazole, 6- methoxybenzothiazole, 6- ethoxyl benzo thiazole, 4,6- dimethyl-benzothiazole, 7- nitro
Any one in benzothiazole.
3. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：Described two
Aryl salt is diphenyl tetrafluoride boron iodine salt, 2- fluorophenyl（Phenyl）Tetrafluoride boron iodine salt, 2- tolyl（Phenyl）Tetrafluoride
Boron iodine salt, 4- nitrobenzophenone（Phenyl）Tetrafluoride boron iodine salt, 2- tolyl（4- tolyl）Tetrafluoride boron iodine salt, two（2- fluorobenzene
Base）Tetrafluoride boron iodine salt, two（4- bromophenyl）Any one in tetrafluoride boron iodine salt, diphenylsulfonium methanesulfonic acid iodine salt.
4. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：Described urge
Agent refer to palladium, Palladous chloride., palladium bromide, palladium iodide, palladium trifluoroacetate, two（Acetylacetone,2,4-pentanedione）One kind of palladium.
5. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：The phosphine
Part refers to that triphenylphosphine, 1,2- are double（Diphenylphosphine）Ethane, 1,1 ＇-bis-（Diphenylphosphine）Ferrocene, 1,3- are double（Diphenyl
Phosphine）Any one in propane, tricyclohexyl phosphine, tri-o-tolyl phosphine.
6. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：The alkali
Refer to the one kind in potassium carbonate, potassium phosphate, potassium tert-butoxide, tetrabutylammonium acetate ammonium, cesium carbonate, triethylamine, pyridine.
7. a kind of preparation method of 2- aryl benzothiazole compound as claimed in claim 1, it is characterised in that：Described molten
Agent refers to N,N-dimethylformamide, 1,2- dichloroethanes, dimethyl sulfoxide, tetrahydrofuran, acetonitrile, toluene, dimethylbenzene, dioxy
One kind in six rings.
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