CN102070563A - Method for preparing 2-benzothiazolylethyl sulfone - Google Patents
Method for preparing 2-benzothiazolylethyl sulfone Download PDFInfo
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- CN102070563A CN102070563A CN 201110023959 CN201110023959A CN102070563A CN 102070563 A CN102070563 A CN 102070563A CN 201110023959 CN201110023959 CN 201110023959 CN 201110023959 A CN201110023959 A CN 201110023959A CN 102070563 A CN102070563 A CN 102070563A
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- ethylmercapto group
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- benzo thiazole
- base ethyl
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Abstract
The invention discloses a method for preparing 2-benzothiazolylethyl sulfone, which takes 2-ethylthiobenzothiazole as a raw material and carbamide peroxide as an oxidant, and comprises the steps of: dissolving the 2-ethylthiobenzothiazole into a reaction solvent, dripping the obtained solution into solution obtained by dissolving the carbamide peroxide into the reaction solvent, and stirring the mixed solution for 4 to 6 hours at room temperature, wherein the molar ratio of the carbamide peroxide to the 2-ethylthiobenzothiazole is 3.5-5.0:1; and adding water and an extraction solvent into an obtained reaction solution, processing an obtained organic layer sequentially through washing, drying and filtration after solution separation, and removing the extraction solvent from an obtained filtrate through vacuum-rotary evaporation to obtain a product, namely the 2-benzothiazolylethyl sulfone. The 2-benzothiazolylethyl sulfone prepared by the method has the characteristics of high yield, low cost, and environmental friendliness and safety.
Description
Technical field
The present invention relates to a kind of synthetic method of organic compound, particularly the synthetic method of 2-[4-morpholinodithio base ethyl sulfone (2-Benzothiazolylethyl sulfone).
Background technology
2-[4-morpholinodithio base ethyl sulfone, its molecular formula are C
9H
9NO
2S
2, its structural formula is shown in S-1, and pure product are white needle-like crystals, and 111.0 ℃ of fusing points are dissolved in methylene dichloride, chloroform, tetracol phenixin, are slightly soluble in ethanol, and are water insoluble.This compound is the important intermediate of Julia-Kocienski alkene reaction.
According to bibliographical information, the synthetic method of 2-[4-morpholinodithio base ethyl sulfone is to generate 2-ethylmercapto group benzo thiazole with the 2-mercaptobenzothiazole alkylation, selects for use suitable oxidant reaction to generate the target product sulfone again.Document V M.Svetlaeva et al, Zh.Obshch.Khim., 1964,34,983. is oxygenant with 30% aqueous hydrogen peroxide solution, and acetate is solvent, reacts under 50～60 ℃ of conditions, and the yield with 60% obtains product, and reaction formula is shown in S-2.Document J.B.Baudin et al, Bull.Soc.Chim.Fr, 1993,130,856. have reported that with 30% aqueous hydrogen peroxide solution be oxygenant, Ammonium Molybdate Tetrahydrate is the reaction of catalyzer, yield 75%, reaction formula is shown in S-3.Patent documentation WO0240459 discloses the synthetic method of another kind of 2-[4-morpholinodithio base ethyl sulfone, be raw material with 2-ethylmercapto group benzo thiazole equally, be oxygenant with metachloroperbenzoic acid (mCPBA) in methylene dichloride, reaction overnight obtains product with 75% yield, and reaction formula is shown in S-4.
More than three kinds of methods exist following defective: be the reaction of oxygenant with the aqueous hydrogen peroxide solution, the danger of blast is arranged when superoxide is accumulated, side reaction simultaneously is more, causes reaction yield low; With the ammonium molybdate is catalyzer, causes the residual of heavy metal ion easily; With the metachloroperbenzoic acid is the reaction of oxygenant, expensive raw material price, and long reaction time (being about 24h), and reaction generates a part m-chlorobenzoic acid, aftertreatment difficulty.
Summary of the invention
The technical problem to be solved in the present invention provides that a kind of yield height, cost are low, the preparation method of the 2-[4-morpholinodithio base ethyl sulfone of green safety.
In order to solve the problems of the technologies described above, the invention provides a kind of preparation method of 2-[4-morpholinodithio base ethyl sulfone, with 2-ethylmercapto group benzo thiazole is raw material, with the urea peroxide is oxygenant, may further comprise the steps: 2-ethylmercapto group benzo thiazole is dissolved in reaction solvent, be added drop-wise in the solution that urea peroxide is dissolved in the reaction solvent gained, stir 4～6h down in room temperature (being generally 10～30 ℃); The mol ratio of urea peroxide and 2-ethylmercapto group benzo thiazole is 3.5～5.0: 1;
In the reaction solution of gained, add entry and extraction solvent, behind the separatory, the organic layer of gained is successively used the washing of saturated sodium carbonate solution and saturated nacl aqueous solution, use anhydrous magnesium sulfate drying again; After the filtration, the filtrate decompression rotary evaporation is removed extraction solvent, obtains product 2-[4-morpholinodithio base ethyl sulfone.
Improvement as the preparation method of 2-[4-morpholinodithio base ethyl sulfone of the present invention: reaction solvent is formic acid or acetate; Total consumption of reaction solvent (promptly being used to dissolve the used reaction solvent of 2-ethylmercapto group benzo thiazole and be used to dissolve the used reaction solvent of urea peroxide) with the ratio of 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000～4000ml reaction solvent/mol.
Further improvement as the preparation method of 2-[4-morpholinodithio base ethyl sulfone of the present invention: extraction solvent is ether, methylene dichloride or chloroform; The amount ratio of extraction solvent and 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000～4000ml extraction solvent/mol.
In the present invention, be the formic acid solution of massfraction 85%～90% as the formic acid of reaction solvent, be analytical pure as the acetate of reaction solvent.
In reaction process of the present invention, when at room temperature stirring, TLC monitoring reaction process treats that raw material (2-ethylmercapto group benzo thiazole) conversion finishes, and finishes reaction, and the reaction times is generally 4～6h.
The preparation method of 2-[4-morpholinodithio base ethyl sulfone of the present invention, it at first is raw material with the 2-mercaptobenzothiazole, with monobromethane prepared in reaction 2-ethylmercapto group benzo thiazole, the system of forming with urea peroxide and acetate or 85% formic acid is an oxygenant again, preparation 2-[4-morpholinodithio base ethyl sulfone.
The reaction equation that the present invention prepares 2-[4-morpholinodithio base ethyl sulfone is as follows:
Wherein, be that the method for raw material and monobromethane prepared in reaction 2-ethylmercapto group benzo thiazole is a known technology with the 2-mercaptobenzothiazole, for example can be with reference to Kendall, J.D.; Suggate, H.G.Journal of the Chemical Society 1949,1503-1509.Specific as follows: 2-mercaptobenzothiazole and ethanol drop into reactor simultaneously, add the NaOH aqueous solution, be heated to reflux state, slow dripping bromine ethane is treated that the 2-mercaptobenzothiazole reaction finishes to be cooled to room temperature, phase-splitting, the organic layer separation is dissolved in methylene dichloride, wash with water, use anhydrous sodium sulfate drying, underpressure distillation to obtain 2-ethylmercapto group benzo thiazole again.
The preparation method of 2-[4-morpholinodithio base ethyl sulfone of the present invention has following advantage:
1, with the urea peroxide be oxygenant, cheap, stability is high, is easy to storage;
2, in contrast to 30%H
2O
2The system of/acetate does not have bringing into of water, has avoided side reactions such as hydrolysis, has improved reaction yield, and reaction is simultaneously at room temperature carried out, and has greatly reduced superoxide and has accumulated the danger that is subjected to thermal explosion;
3, in contrast to the catalytic system of ammonium molybdate, do not have the residual of heavy metal ion;
4, for the system than metachloroperbenzoic acid, by product is a urea, can remove by washing, has simplified post-processing operation;
5, yield height.
Description of drawings
Below in conjunction with accompanying drawing the specific embodiment of the present invention is described in further detail.
Fig. 1 is a 2-ethylmercapto group benzo thiazole
1The HNMR spectrogram.
Fig. 2 is a 2-[4-morpholinodithio base ethyl sulfone
1The HNMR spectrogram.
Embodiment
The preparation method of embodiment 1, a kind of 2-ethylmercapto group benzo thiazole is a starting raw material with the 2-mercaptobenzothiazole, carries out following steps successively:
Three mouthfuls of round-bottomed flasks of 1000mL are mixed the mechanical stirring oar, spherical condensation tube, and constant pressure funnel adds industrial alcohol (being that percent by volume is 95% aqueous ethanolic solution) 250mL and mass concentration 20% aqueous sodium hydroxide solution 160mL, is heated to backflow.The disposable input flask of 2-mercaptobenzothiazole 100g stirs and obtains faint yellow clarifying reaction liquid.Measure the 50mL monobromethane, in 1h, dropwise add flask, dropwise and continue reaction 2h, find that through the TLC monitoring raw material (2-mercaptobenzothiazole) is exhausted.Question response liquid is cooled to room temperature, is divided into two-phase, after lower floor's organic phase is told, adds the 50mL methylene dichloride, and washes with water three times, dewaters with anhydrous sodium sulfate drying again.Underpressure distillation obtains faint yellow product 98g (yield 84%), 27.0～28.2 ℃ of melting ranges.Product is a 2-ethylmercapto group benzo thiazole, confirms that through nmr analysis structure is correct.
The preparation method of embodiment 2, a kind of 2-[4-morpholinodithio base ethyl sulfone, with 2-ethylmercapto group benzo thiazole is starting raw material, carry out following steps successively: with urea peroxide (18.8g, 0.2mol) be dissolved in the formic acid of 100mL mass concentration 85%, be transferred in the 250mL there-necked flask that mechanical stirring oar, thermometer are housed, open and stir.(9.77g 50.0mmol) is dissolved in 50mL 85% formic acid to 2-ethylmercapto group benzo thiazole, changes constant pressure funnel over to, slowly splashes in the flask.TLC detects, and the adularescent solid is separated out in the reaction, and raw material behind the 4h (2-ethylmercapto group benzo thiazole) primitive reaction finishes stopped reaction.
In the reaction solution of gained, add entry 200mL, shake up the back and add ether 150mL, tell upper organic phase (for organic layer), with saturated sodium carbonate solution washing (25mL * 3), use saturated common salt water washing (25mL * 3) again, add the 2g anhydrous magnesium sulfate drying at last; Filter, the diethyl ether solution of gained boils off the ether (15mmHg, 30 ℃) as extraction solvent on Rotary Evaporators, obtain white needles solid 10.4g (yield 91.5%), 112.5～113.0 ℃ of melting ranges.Product is 2-[4-morpholinodithio base ethyl sulfone (purity＞99%), confirms that through nmr analysis structure is correct.
Table 1
At last, it is also to be noted that what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (5)
1. the preparation method of 2-[4-morpholinodithio base ethyl sulfone, it is characterized in that: with 2-ethylmercapto group benzo thiazole is raw material, with the urea peroxide is oxygenant, may further comprise the steps successively: 2-ethylmercapto group benzo thiazole is dissolved in reaction solvent, be added drop-wise in the solution that urea peroxide is dissolved in the reaction solvent gained, under room temperature, stir 4 ~ 6 h; The mol ratio of described urea peroxide and 2-ethylmercapto group benzo thiazole is 3.5 ~ 5.0:1;
In the reaction solution of gained, add entry and extraction solvent, behind the separatory, the organic layer of gained is successively used the washing of saturated sodium carbonate solution and saturated nacl aqueous solution, use anhydrous magnesium sulfate drying again; After the filtration, the filtrate decompression rotary evaporation is removed extraction solvent, obtains product 2-[4-morpholinodithio base ethyl sulfone.
2. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 1 is characterized in that: described reaction solvent is formic acid or acetate.
3. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 2 is characterized in that: total consumption of described reaction solvent with the ratio of 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000 ~ 4000 ml reaction solvent/mol.
4. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 3 is characterized in that: described extraction solvent is ether, methylene dichloride or chloroform.
5. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 4 is characterized in that: the amount ratio of described extraction solvent and 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000 ~ 4000 ml extraction solvent/mol.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107698580A (en) * | 2017-09-28 | 2018-02-16 | 上海彩迩文生化科技有限公司 | A kind of benzothiazole sulfone compound, its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3519630A (en) * | 1969-02-06 | 1970-07-07 | Pennsalt Chemicals Corp | Antibacterial and antifungal treatment with sulfones |
| WO2002040459A1 (en) * | 2000-11-17 | 2002-05-23 | Bayer Cropscience Gmbh | Preparation of monofluoroalkenes |
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2011
- 2011-01-21 CN CN2011100239593A patent/CN102070563B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3519630A (en) * | 1969-02-06 | 1970-07-07 | Pennsalt Chemicals Corp | Antibacterial and antifungal treatment with sulfones |
| WO2002040459A1 (en) * | 2000-11-17 | 2002-05-23 | Bayer Cropscience Gmbh | Preparation of monofluoroalkenes |
Non-Patent Citations (2)
| Title |
|---|
| 《Tetrahedron Letters》 20071205 Benjamin Bourdon, et al. Synthesis of enol ethers from lactones using modified Julia olefination reagents: application to the preparation of tri- and tetrasubstituted exoglycals 747-749 1-5 第49卷, 2 * |
| 《Tetrahedron Letters》 20080711 Laura Palombi, et al. Electro- and acid-catalysis in tetrafluoroborate-based ionic liquid: new alternative routes for the oxidation of sulfides with UHP 5611-5613 1-5 第49卷, 2 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107698580A (en) * | 2017-09-28 | 2018-02-16 | 上海彩迩文生化科技有限公司 | A kind of benzothiazole sulfone compound, its preparation method and application |
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