CN102675241B - Method for synthesizing multi-substituted benzothiazole derivative - Google Patents
Method for synthesizing multi-substituted benzothiazole derivative Download PDFInfo
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- CN102675241B CN102675241B CN201210132444.1A CN201210132444A CN102675241B CN 102675241 B CN102675241 B CN 102675241B CN 201210132444 A CN201210132444 A CN 201210132444A CN 102675241 B CN102675241 B CN 102675241B
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- disulphide
- aldehyde
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- YYYOQURZQWIILK-UHFFFAOYSA-N Nc1ccccc1SSc1ccccc1N Chemical compound Nc1ccccc1SSc1ccccc1N YYYOQURZQWIILK-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention provides a method for synthesizing a multi-substituted benzothiazole derivative by using o-amino disulfide and aldehyde as raw materials, and relates to the technical field of medicine. The synthesizing method comprises the following steps of: dissolving the o-amino disulfide and the aldehyde into a proper solvent, reacting for 10 to 30 minutes at room temperature, and thus obtaining a product. The o-amino disulfide and the aldehyde which are simple, readily available and convenient to use are used as the raw materials and reacted under the catalyst of a cheap iron salt to quickly and efficiently synthesize the multi-substituted benzothiazole derivative. The method has the advantages that the raw materials are readily available, the operation is convenient, the reaction conditions are mild, the yield is high and the like.
Description
Technical field
The present invention relates to medical technical field, particularly relate to the synthetic method of a kind of polysubstituted benzo thiazole derivative.
Background technology
Polysubstituted benzo thiazole derivative is the extremely important heterogeneous ring compound of a class, is widely used in agricultural chemicals, material engineering, medicine and other fields.In agricultural, it has anti-agricultural fungi, desinsection, kills mite, nematicide, Antiphytoviral, weeding isoreactivity; In material engineering field, it can be used as thiofide, dyeing of plastics agent, liquid crystal display material, electroluminescent material, photochromics and fluorescence probe material etc.Pharmaceutically, it can be used as sterilant, fungicides, parasiticide, can also be used for the treatment of diabetes, senile dementia and diagnostic reagent, tuberculosis disease, wind resistance diseases caused by dampness, antitumor as tumour, also has Study On The Radioprotective.Taking the adjacent amido disulphide of fragrance as raw material, the condition of synthetic benzothiazole analog derivative is harsher at present, need anhydrous and oxygen-free, high temperature or use the special reagents such as reductive agent, some synthesis steps are more numerous and diverse, operate more difficult, cost is high, is not easy to suitability for industrialized production.
Summary of the invention
The object of this invention is to provide a kind of easy and simple to handle, reaction conditions is gentle, the method for the synthetic polysubstituted benzo thiazole derivative of with low cost and high productivity.
The concrete grammar of synthetic polysubstituted benzo thiazole derivative provided by the present invention is, the adjacent amido disulphide of raw material fragrance is dissolved in suitable solvent, add molysite catalyzer, in reaction solution, add aromatic aldehyde again, stirring reaction 10-30 min under room temperature, reaction solution obtains product after concentrated purification.
Wherein, the adjacent amido disulphide of fragrance that described adjacent amido disulphide is various replacements, wherein R substituting group is alkyl and the combination thereof of hydrogen or monosubstituted, polysubstituted halogen, aryloxy, alkoxyl group, phenyl, amido, C1-C6; Described raw material is before use without processing.
Described solvent is the common solvent such as methyl alcohol, ethanol, propyl alcohol, butanols, methylene dichloride, trichloromethane, tetrahydrofuran (THF), toluene, Isosorbide-5-Nitrae-dioxane, acetone, water and DMF, and described solvent is before use without processing;
Described molysite is iron trichloride, ferric chloride (FeCl36H2O), iron nitrate, ferric sulfate, ferric fluoride, iron bromide, ferric iodide, after purchase, can directly use without processing.
Described aldehyde is the phenyl aldehyde of phenyl aldehyde or replacement, as substituting groups such as the alkyl of ortho position, a position, para-orientation, alkoxyl group, phenyl, amido, nitro, cyano group, halogens, after purchase, uses without processing directly.
The mol ratio of described reaction raw materials is: fragrant adjacent amido disulphide: molysite: aromatic aldehyde=1.0: 0.05-0.2: 1.2.
After having reacted, generally also need to obtain product through 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 synthetic polysubstituted benzo thiazole derivative general structure obtaining of the present invention is suc as formula shown in I.
Reaction formula is as follows:
The present invention uses and is easy to get the adjacent amido disulphide of fragrance stable is raw material, taking nontoxic, be easy to get, inexpensive molysite is as catalyzer, react with multiple aromatic aldehyde, fast and efficiently synthetic polysubstituted benzo thiazole derivative.The present invention has that reaction conditions gentleness, reaction times are short, easy and simple to handle, productive rate advantages of higher.
Embodiment
Synthetic (the R '=H in structural formula) of embodiment 1,6-(3 ,-dimethyl phenoxy)-2-phenyl benzothiazole-5-amine
1,6-(3,5 dimethyl phenoxy)-2-phenyl benzothiazole-5-amine is synthetic
In 25ml round-bottomed flask, add two (4-(3,5-dimethyl phenoxy) benzene-1 of 0.10mmol raw material 6,6 '-bis-sulphur, 3-diamines), 4ml methanol solvate, under agitation makes after material dissolution, add 0.02mmol ferric chloride (FeCl36H2O), and stirring makes its dissolving.Finally add 0.12mmol phenyl aldehyde, at room temperature stirring reaction 10min, TLC detects and finds that disulphide raw material reaction is complete, after employing Rotary Evaporators removes solvent under reduced pressure, obtains crude product.Crude product makees eluent by sherwood oil and ethyl acetate or methylene dichloride and ethyl acetate, adopt gradient elution, carry out after column chromatography for separation (200-300 order silica gel), obtain the white solid 6-(3 that purity is greater than 99%, 5-dimethyl phenoxy)-2-phenyl benzothiazole-5-amine 30.0mg, isolated yield is 43.3%, and fusing point is 136-138 DEG C.
2, the qualification of 6-(3,5-dimethyl phenoxy)-2-phenyl benzothiazole-5-amine
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): 2.33 (s, 6H), 3.99 (brs, 2H), 6.67 (s, 2H), 6.77 (s, 1H), 7.26 (s, 1H), 7.47-7.51 (m, 4H), 8.04 (s, 1H), 8.04 (s, 1H);
13c NMR (CDCl
3, TMS): 21.36,108.23,111.10,115.69,124.62,125.29,127.31,129.00,130.70,133.58,138.46,139.87,144.04,150.90,156.98,167.59.
Mass-spectrometric data: ESIMS calcd for C
21h
18n
2oS 346.45, found 347.01.
Analytical results shows, the object product of acquisition is correct.
Synthetic (the R '=Br in structural formula) of embodiment 2,6-(3,5-dimethyl phenoxy)-2-(4-bromophenyl) benzothiazole-5-amine
1,6-(3,5-dimethyl phenoxy)-2-(4-bromophenyl) benzothiazole-5-amine is synthetic
In 25ml round-bottomed flask, add two (4-(3,5-dimethyl phenoxy) benzene-1 of 0.10mmol raw material 6,6 '-bis-sulphur, 3-diamines), 4ml methanol solvate, under agitation makes after material dissolution, add 0.02mmol ferric chloride (FeCl36H2O), and stirring makes its dissolving.Finally add 0.12mmol p-bromobenzaldehyde, at room temperature stirring reaction 10min, TLC detects and finds that disulphide raw material reaction is complete, after employing Rotary Evaporators removes solvent under reduced pressure, obtains crude product.Crude product makees eluent by sherwood oil and ethyl acetate or methylene dichloride and ethyl acetate, adopt gradient elution, carry out column chromatography for separation (200-300 order silica gel), obtain the Off-white solid 6-(3 that purity is greater than 99%, 5-dimethyl phenoxy)-2-(4-bromophenyl) benzothiazole-5-amine 54.5mg, isolated yield is 64.1%, and fusing point is 192-195 DEG C.
2, the qualification of 6-(3,5-dimethyl phenoxy)-2-(4-bromophenyl) benzothiazole-5-amine
Nuclear magnetic resonance data:
1h NMR (CDCl
3, TMS): .2.30 (s, 6H), 4.04 (brs, 2H), 6.66 (s, 2H), 6.78 (s, 1H), 7.26 (s, 1H) 7.46 (s, 1H), 7.59 (d, 2H, J=8.5Hz), 7.90 (d, 2H, J=8.5Hz);
13c NMR (CDCl
3, TMS): 21.35,108.34,111.05,115.72,124.82,124.84,125.32,128.59,132.13,132.83,138.54,139.87,144.17,151.31,156.93,166.04.
Mass-spectrometric data: EIMS calcd for C
21h
17brN
2oS 425.34, found 426.02.
Analytical results shows, the object product of acquisition is correct.
Synthetic (the R '=OCH in structural formula of embodiment 3,6-(3 ,-dimethyl phenoxy)-2-(4-p-methoxy-phenyl) benzothiazole-5-amine
3)
1,6-(3,5-dimethyl phenoxy)-2-(4-p-methoxy-phenyl) benzothiazole-5-amine
In 25ml round-bottomed flask, add two (4-(3,5-dimethyl phenoxy) benzene-1 of 0.10mmol raw material 6,6 '-bis-sulphur, 3-diamines), 4ml methanol solvate, under agitation makes after material dissolution, add 0.02mmol ferric chloride (FeCl36H2O), and stirring makes its dissolving.Finally add 0.12mmol aubepine, at room temperature stirring reaction 10min, TLC detects and finds that disulphide raw material reaction is complete, after employing Rotary Evaporators removes solvent under reduced pressure, obtains crude product.Crude product makees eluent by sherwood oil and ethyl acetate or methylene dichloride and ethyl acetate, adopt gradient elution, carry out column chromatography for separation (200-300 order silica gel), obtain the Off-white solid 6-(3 that purity is greater than 99%, 5-dimethyl phenoxy)-2-(4-p-methoxy-phenyl) benzothiazole-5-amine 42.4mg, isolated yield is 56.3%, and fusing point is 132-136 DEG C.
2, the qualification of 6-(3,5-dimethyl phenoxy)-2-(4-p-methoxy-phenyl) benzothiazole-5-amine
Nuclear magnetic resonance data:
1h NMR (300MHz, DMSO-d
6): .2.22 (s, 6H), 3.83 (s, 3H), 5.11 (brs, 2H), 6.58 (s, 2H), 6.72 (s, 1H), 7.06-7.09 (m, 2H), 7.34 (s, 1H), 7.44 (s, 1H), 7.92-7.95 (m, 2H);
13c NMR (125MHz, DMSO-d
6): 20.89,55.40,106.80,112.47,114.59,114.68,121.52,124.30,125.99,128.34,139.05,140.39,141.94,151.57,157.36,161.29,166.14.
Mass-spectrometric data: EIMS calcd for C
22h
20n
2o
2s 376.47, found 376.06.
Analytical results shows, the object product of acquisition is correct.
Claims (4)
1. a method for synthetic polysubstituted benzo thiazole derivative taking adjacent amido disulphide and aldehyde as raw material, is dissolved in adjacent amido disulphide and aldehyde in solvent, obtains product after then adding ferric chloride catalyst to react 10-30min under the condition of room temperature
the adjacent amido disulphide of fragrance that described adjacent amido disulphide is various replacements
wherein R substituting group is alkyl and the combination thereof of hydrogen or monosubstituted, polysubstituted halogen, phenyl, C1-C6; Described aldehyde is substituted benzaldehyde
wherein R ' is hydrogen or ortho position, a position, the phenyl of para-orientation, nitro, cyano group, halogen; Described reaction raw materials mol ratio is adjacent amido disulphide: iron trichloride: aromatic aldehyde=1.0: 0.05-0.2: 1.2.
2. the method for synthetic polysubstituted benzo thiazole derivative according to claim 1, is characterized in that: described iron trichloride is ferric chloride (FeCl36H2O).
3. synthetic method according to claim 1, is characterized in that: described solvent is methyl alcohol, ethanol, propyl alcohol, butanols, and described solvent is before use without processing.
4. the method for synthetic polysubstituted benzo thiazole derivative according to claim 1, is characterized in that: described in obtain product needed through purification process.
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| CN103408505B (en) * | 2013-07-17 | 2015-11-25 | 内蒙古工业大学 | A kind of is the method that Material synthesis 2-replaces benzo thiazole derivative with carboxylic acid and disulphide |
| CN104761536B (en) * | 2015-03-12 | 2017-05-10 | 内蒙古工业大学 | Method of synthesizing 2-substituted benzothiazole-type derivative |
| CN105884714B (en) * | 2016-05-03 | 2018-11-23 | 内蒙古工业大学 | A kind of green syt 2- replaces the method for benzo thiazole derivative |
| CN105949147B (en) * | 2016-05-26 | 2018-10-19 | 内蒙古工业大学 | A kind of method of green syt 2-mercaptobenzothiazole analog derivative |
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| WO2008076916A2 (en) * | 2006-12-15 | 2008-06-26 | Molecular Devices Corporation | Thallium-sensitive agents and methods of using the same |
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| CN102272132A (en) * | 2008-11-06 | 2011-12-07 | 首尔大学教产学协力团 | Fluorinated benzothiazole derivatives, preparation method thereof and imaging agent for diagnosing altzheimer's disease using the same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008076916A2 (en) * | 2006-12-15 | 2008-06-26 | Molecular Devices Corporation | Thallium-sensitive agents and methods of using the same |
| EP2364976A1 (en) * | 2007-03-21 | 2011-09-14 | EPIX Pharmaceuticals, Inc. | S1P receptor modulating compounds and use thereof |
| CN102272132A (en) * | 2008-11-06 | 2011-12-07 | 首尔大学教产学协力团 | Fluorinated benzothiazole derivatives, preparation method thereof and imaging agent for diagnosing altzheimer's disease using the same |
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