CN104098528A - 2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide - Google Patents
2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide Download PDFInfo
- Publication number
- CN104098528A CN104098528A CN201410380338.4A CN201410380338A CN104098528A CN 104098528 A CN104098528 A CN 104098528A CN 201410380338 A CN201410380338 A CN 201410380338A CN 104098528 A CN104098528 A CN 104098528A
- Authority
- CN
- China
- Prior art keywords
- synthetic method
- raw material
- mercaptobenzothiazole
- metal sulfide
- inorganic metal
- 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.)
- Pending
Links
- YXIWHUQXZSMYRE-UHFFFAOYSA-N Sc1nc(cccc2)c2[s]1 Chemical compound Sc1nc(cccc2)c2[s]1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
- C07D277/72—2-Mercaptobenzothiazole
-
- 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
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention relates to the technical field of agriculture, industry and pharmacy and provides a 2-mercapto benzothiazole derivative synthetic method. According to the 2-mercapto benzothiazole derivative synthetic method, 2-mercapto benzothiazole derivatives are synthesized by take 2-halogen phenylamine, carbon disulfide and inorganic metal sulfide as the raw materials and through catalysis of copper salt. The method comprises dissolving the 2-halogen phenylamine, the inorganic metal sulfide and copper salt catalyst inside an appropriate solvent, adding the carbon disulfide inside the mixture for recreation under 50-110 DEG C for a certain time and performing purification treatment to obtain the 2-mercapto benzothiazole derivatives. The 2-mercapto benzothiazole derivative synthetic method with the copper-catalyzed carbon disulfide is rapid and efficiency, by taking the nontoxic, cheap and easily-obtained copper salt as the catalyst, omits ligand for recreations, and has the advantages of being high in yield rate, mild in conditions, low in the amount of by-products and the like.
Description
Technical field
The present invention relates to agricultural, industry and medical technical field, particularly relate to a kind of synthetic method of benzothiazole analog derivative of 2-sulfydryl replacement.
Background technology
2-mercaptobenzothiazole analog derivative is the important component part of benzothiazole compound, in agricultural, industry and field of medicaments extensive application, is worth.In agricultural, 2-mercaptobenzothiazole is the intermediate of synthetic herbicide mefenacet.Industrial, 2-mercaptobenzothiazole, as general purpose rubber vulcanization accelerator, is widely used in and promotes natural rubber and elastomeric sulfuration.At field of medicaments, 2-mercaptobenzothiazole compounds has the functions such as anticancer, antibacterial, also can be used as protease inhibitor simultaneously.In addition, 2-mercaptobenzothiazole also for the preparation of mycocide, nitrogen fertilizer potentiating agent, cut organic anti-fogging agent in disappear oil and slip additive, photographic chemistry, metal corrosion inhibitor etc.Therefore, the research of 2-mercaptobenzothiazole analog derivative and application enjoy the concern of researcher.
The synthetic method of 2-mercaptobenzothiazole is a lot, there are o-Nitrochlorobenzene method, aniline process, nitrobenzene method, nitrosobenzene method, benzothiazole method, oil of mirbane and aniline hybrid system, methylphenylamine method, N, dinethylformamide method, dimethylamine method, halo aniline process and near amino thiophenols method etc., but these methods are long reaction time mostly, productive rate is not high, and by product is more.
Summary of the invention
The object of the invention is to utilize dithiocarbonic anhydride, adjacent halobenzene amine and inorganic metal sulfide is raw material, and mantoquita is catalyzer, and a kind of novel method of a kind of mild condition, the synthetic 2-mercaptobenzothiazole analog derivative of simple to operate, high yield is provided.
The concrete grammar of synthetic 2-mercaptobenzothiazole analog derivative provided by the present invention is; adjacent halobenzene amine, inorganic metal sulfide and copper salt catalyst are dissolved in suitable solvent; under the protection of rare gas element, add dithiocarbonic anhydride; at 50-110 ℃, react certain hour; after TLC detection raw material reaction is complete; be cooled to room temperature and add mineral acid, then reaction mixture is finally obtained to product through purification process.
The adjacent halobenzene amine of described raw material as shown in the formula, wherein X is chlorine, bromine and iodine, R substituting group is alkoxyl group, trifluoromethyl, phenyl, the amido of hydrogen or monosubstituted, polysubstituted halogen, phenoxy group, C1-C6, alkyl and the combination thereof of C1-C6; Described inorganic metal sulfide is nine water cure sodium, Sodium sulphate anhydrous, 99min, nine water cure potassium and anhydrous potassium sulphide, and described raw material is before use without processing.
Described solvent is DMF, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO) and ethanol, and solvent for use is before use without processing.
Described copper salt catalyst is cuprous chloride, cuprous iodide, neutralized verdigris, after purchase, can directly use without special processing.
Described reaction raw materials mol ratio is: adjacent halobenzene amine: dithiocarbonic anhydride: inorganic metal sulfide: mantoquita=1.0: 1.2-5.0: 0.3-2.0: 0.05-0.1.
After having reacted, reaction solution need be cooled to room temperature, add dilute hydrochloric acid acidifying (1N-4N), then with ethyl acetate or dichloromethane extraction, extraction liquid obtains product after concentrated and purge process.Described concentration process is to adopt the methods such as air distillation, underpressure distillation, as uses Rotary Evaporators vacuum concentration.Described purge process refers to column chromatography or recrystallization separating and purifying technology.The general structure of the synthetic 2-mercaptobenzothiazole analog derivative obtaining of the present invention is suc as formula shown in I.
Reaction formula is as follows:
X＝I，Br，Cl；Y＝Na，K
It is raw material that adjacent halobenzene amine, dithiocarbonic anhydride and inorganic metal sulfide are take in the present invention, utilizes mantoquita nontoxic, cheap and easy to get for the synthetic method of catalyst development 2-mercaptobenzothiazole analog derivative.Synthetic method of the present invention is raw materials used inexpensive, nontoxic, pollution-free, and synthetic method has reaction conditions gentleness, easy and simple to handle, productive rate advantages of higher.
Embodiment
Embodiment 1, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (90 ℃ of temperature of reaction) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 1.00mmol (0.2402g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL solvent N, the dithiocarbonic anhydride of dinethylformamide and 2.50mmol (0.1904g), at 90 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 68.1mg that purity is greater than 99%, isolated yield is 81.5%, and fusing point is 176-179 ℃.
Embodiment 2, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (50 ℃ of temperature of reaction) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 1.00mmol (0.2402g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 2.50mmol (0.1904g), at 50 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 60.4mg that purity is greater than 99%, isolated yield is 72.2%, and fusing point is 177-179 ℃.
Embodiment 3, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (70 ℃ of temperature of reaction) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 68.5mg that purity is greater than 99%, isolated yield is 82.0%, and fusing point is 176-178 ℃.
Embodiment 4, take adjacent Iodoaniline as synthetic 2-mercaptobenzothiazole (the adjacent Iodoaniline: dithiocarbonic anhydride: nine water cure sodium=1: 3: 0.3) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 0.15mmol (0.0360g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 51.0mg that purity is greater than 99%, isolated yield is 61.0%, and fusing point is 175-177 ℃.
Embodiment 5, take adjacent Iodoaniline as synthetic 2-mercaptobenzothiazole (the adjacent Iodoaniline: dithiocarbonic anhydride: nine water cure sodium=1: 1.2: 0.5) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 0.60mmol (0.0457g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 37.9mg that purity is greater than 99%, isolated yield is 45.3%, and fusing point is 176-178 ℃.
Embodiment 6, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (adjacent Iodoaniline: dithiocarbonic anhydride: potassium sulphide=1: 3: 0.5) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the cuprous iodide of the potassium sulphide of 0.25mmol (0.0276g) and 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, dinethylformamide does and the dithiocarbonic anhydride of 1.50mmol (0.1142g), under 70 ℃ of stirrings, react 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 60.7mg that purity is greater than 99%, isolated yield is 72.6%, and fusing point is 177-178 ℃.
Embodiment 7, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (cuprous chloride is made catalyzer) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 1.00mmol (0.2402g) and the cuprous chloride of 0.05mmol (0.0049g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 2.50mmol (0.1904g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3 mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 25.9mg that purity is greater than 99%, isolated yield is 31.0%, and fusing point is 176-179 ℃.
Embodiment 8, take adjacent Iodoaniline as the synthetic 2-mercaptobenzothiazole (neutralized verdigris is made catalyzer) of raw material
The adjacent Iodoaniline that adds 0.50mmol (0.1095g) in reaction tube, the nine water cure sodium of 1.00mmol (0.2402g) and the neutralized verdigris of 0.05mmol (0.0100g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 2.50mmol (0.1904g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 60.1mg that purity is greater than 99%, isolated yield is 71.9%, and fusing point is 176-177 ℃.
Embodiment 9, take o-bromoaniline as the synthetic 2-mercaptobenzothiazole of raw material
The o-bromoaniline that adds 0.50mmol (0.0860g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3 mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 27.0mg that purity is greater than 99%, isolated yield is 32.3%, and fusing point is 178-180 ℃.
Embodiment 10, take Ortho-Chloro aniline as the synthetic 2-mercaptobenzothiazole of raw material
The Ortho-Chloro aniline that adds 0.50mmol (0.0638g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the pale yellow powder 2-mercaptobenzothiazole 37.9mg that purity is greater than 99%, isolated yield is 45.4%, and fusing point is 177-179 ℃.
The evaluation of 2-mercaptobenzothiazole
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): 7.27-7.39 (m, 3H), 7.48 (d, 1H, J=8.0Hz), 11.41 (brs, 1H).
Mass-spectrometric data: EIMS calcd for C
7h
5nS
2167.99 found 168.19.
Analytical results shows, the target product of acquisition is correct.
The fluoro-2-Iodoaniline of embodiment 11, the 4-of take is the synthetic fluoro-2-mercaptobenzothiazole of 6-of raw material
1, the fluoro-2-Iodoaniline of 4-that adds 0.50mmol (0.1185g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain the fluoro-2-mercaptobenzothiazole 58.3mg of white powder 6-that purity is greater than 99%, isolated yield is 63.0%, and fusing point is 205-209 ℃.
2, the evaluation of the fluoro-2-mercaptobenzothiazole of 6-
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): 7.11 (dt, 1H, J=9.0Hz, 2.5Hz), 7.21 (dd, 1H, J=7.5Hz, 2.5Hz), 7.24 (dd, 1H, J=9.0Hz, 4.5Hz), 11.05 (brs, 1H).
Mass-spectrometric data: ESIMS calcd for C
7h
4fNS
2185.98 found 185.19.
Analytical results shows, the target product of acquisition is correct.
The iodo-4-monomethylaniline of embodiment 12, the 2-of take is the synthetic 6-methyl-2-mercaptobenzothiazole of raw material
1, the iodo-4-monomethylaniline of 2-that adds 0.50mmol (0.1165g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain pale yellow powder 6-methyl-2-mercaptobenzothiazole 66.1mg that purity is greater than 99%, isolated yield is 73.0%, and fusing point is 150-152 ℃.
2, the evaluation of 6-methyl-2-mercaptobenzothiazole
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): 7.23,7.18,7.16,2.41,11.89 (brs, 1H);
13c NMR (CDCl
3, TMS): 138.17,134.92,130.12,128.31,121.36,111.96,77.03,190.22;
Mass-spectrometric data: ESIMS calcd for C
8h
7nS
2182.00 found 181.74.
Analytical results shows, the target product of acquisition is correct
Embodiment 13, the iodo-4-of the 2-of take (trifluoromethyl) aniline are the synthetic 6-trifluoromethyl-2-mercaptobenzothiazole of raw material
1, the iodo-4-of 2-(trifluoromethyl) aniline that adds 0.50mmol (0.1435g) in reaction tube, the nine water cure sodium of 0.25mmol (0.0600g) and the cuprous iodide of 0.05mmol (0.0095g), under the environment of rare gas element, add again 2mL N, the dithiocarbonic anhydride of dinethylformamide and 1.50mmol (0.1142g), at 70 ℃, stirring reaction is 8 hours, after TLC detects adjacent Iodoaniline and reacts completely, reaction solution is cooled to room temperature, add the hydrochloric acid of 3mL4N to stir 15min, then by dichloromethane extraction three times of this reaction solution, merge organic phase, anhydrous magnesium sulfate drying removed by filter siccative after 2 hours, finally remove dichloromethane solvent under reduced pressure and obtain crude product.Crude product carries out column chromatography for separation (200-300 order silica gel), adopt sherwood oil and ethyl acetate to carry out gradient elution (8: 1-2: 1), obtain white powder 6-trifluoromethyl-2-mercaptobenzothiazole 77.5mg that purity is greater than 99%, isolated yield is 65.9%, and fusing point is 251-253 ℃.
2, the evaluation of 6-trifluoromethyl-2-mercaptobenzothiazole
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): 7.38-7.74 (m, 3H), 11.07 (brs, 1H);
13c NMR (CDCl
3, TMS): 191.98,142.19,130.35,127.25,124.75,122.58,118.90,111.86.
Mass-spectrometric data: ESIMS calcd for C
8h
4f
3nS
2235.97 found 235.46.
Analytical results shows, the target product of acquisition is correct.
Claims (8)
1. take adjacent halobenzene amine, dithiocarbonic anhydride and the inorganic metal sulfide method as raw material synthetic 2-mercaptobenzothiazole analog derivative under mantoquita catalysis for one kind, adjacent halobenzene amine, inorganic metal sulfide and copper salt catalyst are dissolved in organic solvent, after adding dithiocarbonic anhydride, at 50-110 ℃, react certain hour, cooling, acidizing neutralization after TLC detection raw material reaction is complete, then carry out obtaining product after purification process
wherein R group comes from adjacent halobenzene amine.
2. synthetic method according to claim 1, is characterized in that: the structural formula of the adjacent halobenzene amine of described raw material is
wherein X is chlorine, bromine or iodine, and R substituting group is alkoxyl group, trifluoromethyl, phenyl, the amino of hydrogen or monosubstituted, polysubstituted halogen, phenoxy group, C1-C6, alkyl and the combination thereof of C1-C6, and described raw material is before use without processing.
3. synthetic method according to claim 1, is characterized in that: described raw material inorganic metal sulfide is nine water cure sodium, Sodium sulphate anhydrous, 99min, nine water cure potassium and anhydrous potassium sulphide, and described raw material is before use without processing.
4. synthetic method according to claim 1, is characterized in that: the mantoquita in described synthetic method is cuprous chloride, cuprous iodide, neutralized verdigris, after purchase, can directly use without special processing.
5. synthetic method according to claim 1, is characterized in that: the organic solvent in described synthetic method is DMF, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO) and ethanol, and solvent for use is before use without processing.
6. synthetic method according to claim 1, is characterized in that: described reaction raw materials mol ratio is adjacent halobenzene amine: dithiocarbonic anhydride: inorganic metal sulfide: mantoquita=1.0: 1.2-5.0: 0.3-2.0: 0.05-0.1.
7. synthetic method according to claim 1, is characterized in that: the hydrochloric acid that in described synthetic method, acidifying mineral acid used is 1-4mol/L.
8. synthetic method according to claim 1, is characterized in that: described in the product needed that obtains through column chromatography, carry out purification process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410380338.4A CN104098528A (en) | 2014-08-05 | 2014-08-05 | 2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410380338.4A CN104098528A (en) | 2014-08-05 | 2014-08-05 | 2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104098528A true CN104098528A (en) | 2014-10-15 |
Family
ID=51667114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410380338.4A Pending CN104098528A (en) | 2014-08-05 | 2014-08-05 | 2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104098528A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108017594A (en) * | 2017-12-14 | 2018-05-11 | 武汉工程大学 | A kind of preparation method of sulfydryl substituted nitrogen heterocyclic cycle compound |
| JP2018531286A (en) * | 2015-10-09 | 2018-10-25 | 聖奥化学科技有限公司Ｓｅｎｎｉｃｓ Ｃｏ．，Ｌｔｄ． | Method for preparing 2-mercaptobenzothiazole |
| CN110845439A (en) * | 2019-11-26 | 2020-02-28 | 南京工业大学 | Method for synthesizing 2-substituted benzothiazole by one-pot method |
| CN111285823A (en) * | 2020-03-01 | 2020-06-16 | 西北工业大学 | Preparation method of naphtho [1,8-de ] [1,3] thiazine-2-thiol |
| CN111704591A (en) * | 2020-07-08 | 2020-09-25 | 衡阳师范学院 | Synthesis method of copper-catalyzed thio-naphthothiazolone compound |
| CN111892553A (en) * | 2020-08-05 | 2020-11-06 | 衡阳师范学院 | Method for synthesizing ammonium acetate mediated benzothiazole compound |
| CN113912564A (en) * | 2021-10-27 | 2022-01-11 | 河南省化工研究所有限责任公司 | Novel method for preparing 2-mercaptobenzothiazole by mild catalytic oxidation of metalloporphyrin |
| CN114644603A (en) * | 2020-12-21 | 2022-06-21 | 内蒙古工业大学 | Method for catalytically activating carbon dioxide as carbonylation reagent by using inorganic sulfur |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070213321A1 (en) * | 2005-05-09 | 2007-09-13 | Hydra Biosciences, Inc. | Compounds for modulating TRPV3 function |
-
2014
- 2014-08-05 CN CN201410380338.4A patent/CN104098528A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070213321A1 (en) * | 2005-05-09 | 2007-09-13 | Hydra Biosciences, Inc. | Compounds for modulating TRPV3 function |
Non-Patent Citations (1)
| Title |
|---|
| 竺宁等: "《2-取代苯并噻唑类衍生物合成方法研究的新进展》", 《有机化学》 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018531286A (en) * | 2015-10-09 | 2018-10-25 | 聖奥化学科技有限公司Ｓｅｎｎｉｃｓ Ｃｏ．，Ｌｔｄ． | Method for preparing 2-mercaptobenzothiazole |
| CN108017594A (en) * | 2017-12-14 | 2018-05-11 | 武汉工程大学 | A kind of preparation method of sulfydryl substituted nitrogen heterocyclic cycle compound |
| CN110845439A (en) * | 2019-11-26 | 2020-02-28 | 南京工业大学 | Method for synthesizing 2-substituted benzothiazole by one-pot method |
| CN110845439B (en) * | 2019-11-26 | 2023-04-11 | 南京工业大学 | Method for synthesizing 2-substituted benzothiazole by one-pot method |
| CN111285823A (en) * | 2020-03-01 | 2020-06-16 | 西北工业大学 | Preparation method of naphtho [1,8-de ] [1,3] thiazine-2-thiol |
| CN111285823B (en) * | 2020-03-01 | 2022-07-26 | 西北工业大学 | Preparation method of naphtho [1,8-de ] [1,3] thiazine-2-thiol |
| CN111704591A (en) * | 2020-07-08 | 2020-09-25 | 衡阳师范学院 | Synthesis method of copper-catalyzed thio-naphthothiazolone compound |
| CN111704591B (en) * | 2020-07-08 | 2023-05-16 | 衡阳师范学院 | Synthesis method of copper-catalyzed thionaphthothiazolone compound |
| CN111892553A (en) * | 2020-08-05 | 2020-11-06 | 衡阳师范学院 | Method for synthesizing ammonium acetate mediated benzothiazole compound |
| CN114644603A (en) * | 2020-12-21 | 2022-06-21 | 内蒙古工业大学 | Method for catalytically activating carbon dioxide as carbonylation reagent by using inorganic sulfur |
| CN113912564A (en) * | 2021-10-27 | 2022-01-11 | 河南省化工研究所有限责任公司 | Novel method for preparing 2-mercaptobenzothiazole by mild catalytic oxidation of metalloporphyrin |
| CN113912564B (en) * | 2021-10-27 | 2023-01-31 | 河南省化工研究所有限责任公司 | Method for preparing 2-mercaptobenzothiazole by mild catalytic oxidation of metalloporphyrin |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104098528A (en) | 2-mercapto benzothiazole derivative synthetic method with copper-catalyzed carbon disulfide | |
| Bao et al. | Molecular iodine-mediated synthesis of thiocarbamates from thiols, isocyanides and water under metal-free conditions | |
| US20220340520A1 (en) | Rreparation method of 3-mercaptopropionic acid | |
| CN102911135B (en) | The synthetic method of 2-mercaptobenzothiazole analog derivative | |
| Tong et al. | A simple approach to benzothiazoles from 2-chloronitrobenzene, elemental sulfur, and aliphatic amine under solvent-free and catalyst-free conditions | |
| Wang et al. | A general method for synthesis of Se-trifluoromethyl esters through Iron-catalyzed trifluoromethylselenolation of acid chlorides | |
| CN109206335B (en) | Process for preparing ortho-trifluoromethylanilines and intermediates thereof | |
| CA2829866A1 (en) | 1,2-benzisothiazol-3-one compound production method | |
| JP2008529986A (en) | Intermediate preparation method | |
| JP2013043882A (en) | Method for producing 1,2-benzisothiazolin-3-one compound | |
| CN103408505B (en) | A kind of is the method that Material synthesis 2-replaces benzo thiazole derivative with carboxylic acid and disulphide | |
| WO2009122834A1 (en) | Method for producing 4-perfluoroisopropylaniline | |
| CN102675241B (en) | Method for synthesizing multi-substituted benzothiazole derivative | |
| CN105566260B (en) | A kind of preparation method of frusemide | |
| CN104098529B (en) | Inorganic metal sulfide promotes the method for dithiocarbonic anhydride and adjacent halobenzene amine Reactive Synthesis 2-mercaptobenzothiazole | |
| CN104046351B (en) | There is the luminous organic material of afterglow performance and synthetic method thereof and application | |
| CN104829553A (en) | New method of synthesizing 2,4-di-substituted benzothiazole | |
| JP2007186453A (en) | Method for producing thiazole compound | |
| US8586792B2 (en) | Process for the preparation of 4-iodo-3-nitrobenzamide | |
| WO2014208296A1 (en) | Method for manufacturing nitrobenzene compound | |
| CA2930089C (en) | Fingolimod hydrochloride process | |
| WO2015113192A1 (en) | Benzo-lactam compound, synthesis method and application thereof | |
| CN103922975B (en) | Synthesis method of sulfonamide compound | |
| CN104230713B (en) | The method for being used to prepare 2- (2- hydroxy phenyl) alkyl acetate | |
| JP4869739B2 (en) | Fluorine-containing dihydroquinoline compound and method for producing fluorine-containing quinoline compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20141015 |