CN102070563B - Method for preparing 2-benzothiazolylethyl sulfone - Google Patents
Method for preparing 2-benzothiazolylethyl sulfone Download PDFInfo
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- CN102070563B CN102070563B CN2011100239593A CN201110023959A CN102070563B CN 102070563 B CN102070563 B CN 102070563B CN 2011100239593 A CN2011100239593 A CN 2011100239593A CN 201110023959 A CN201110023959 A CN 201110023959A CN 102070563 B CN102070563 B CN 102070563B
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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 compound method of organic cpds, particularly the compound 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 article 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 compound 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 title 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, under 50～60 ℃ of conditions, reacts, 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 compound method of another kind of 2-[4-morpholinodithio base ethyl sulfone; Be raw material with 2-ethylmercapto group benzo thiazole equally; In methylene dichloride, be oxygenant with metachloroperbenzoic acid (mCPBA), 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, the aftertreatment difficulty.
Summary of the invention
The technical problem that the present invention will solve provides that a kind of yield is high, cost is 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 present invention provides a kind of preparation method of 2-[4-morpholinodithio base ethyl sulfone; With 2-ethylmercapto group benzo thiazole is raw material, is oxygenant with the urea peroxide, 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 successively with saturated sodium carbonate solution and saturated nacl aqueous solution washing, is used 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 again is an oxygenant, preparation 2-[4-morpholinodithio base ethyl sulfone.
The reaction equation that the present invention prepares 2-[4-morpholinodithio base ethyl sulfone is following:
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 drum simultaneously, add the NaOH aqueous solution, are 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; Use water washing, 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 receives 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 through washing, has simplified post-processing operation;
5, yield is high.
Description of drawings
Do further explain below in conjunction with the accompanying drawing specific embodiments of the invention.
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 phases, after lower floor's organic phase is told, adds the 50mL methylene dichloride, and with water washing 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, TM 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),, use saturated common salt water washing (25mL * 3) again, add the 2g anhydrous magnesium sulfate drying at last with saturated sodium carbonate solution washing (25mL * 3); 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.
Embodiment 3～6 is identical with elementary operation with substrate (the 2-ethylmercapto group benzo thiazole) consumption of embodiment 2; But the total amount (promptly be 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) of urea peroxide (UHP) consumption, used reaction solvent) and extraction solvent different; Therefore each condition and the result with embodiment 2～6 classifies table 1 as, so that contrast.The purity of products therefrom 2-[4-morpholinodithio base ethyl sulfone all＞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 (4)
1.2-the preparation method of benzothiazolyl 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, is added drop-wise in the solution that urea peroxide is dissolved in the reaction solvent gained, under room temperature, stir 4～6h; The mol ratio of said urea peroxide and 2-ethylmercapto group benzo thiazole is 3.5～5.0: 1; Said reaction solvent is formic acid or acetate;
In the reaction solution of gained, add entry and extraction solvent, behind the separatory, the organic layer of gained successively with saturated sodium carbonate solution and saturated nacl aqueous solution washing, is used 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: total consumption of said reaction solvent with the ratio of 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000～4000ml reaction solvent/mol.
3. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 2 is characterized in that: said extraction solvent is ether, methylene dichloride or chloroform.
4. the preparation method of 2-[4-morpholinodithio base ethyl sulfone according to claim 3 is characterized in that: the amount ratio of said extraction solvent and 2-ethylmercapto group benzo thiazole is: the 2-ethylmercapto group benzo thiazole of 2000～4000ml extraction solvent/mol.
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