CN105085343A - Preparation method of disulfide compound 3,3'-dithiodipropionic acid - Google Patents
Preparation method of disulfide compound 3,3'-dithiodipropionic acid Download PDFInfo
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- CN105085343A CN105085343A CN201510569327.5A CN201510569327A CN105085343A CN 105085343 A CN105085343 A CN 105085343A CN 201510569327 A CN201510569327 A CN 201510569327A CN 105085343 A CN105085343 A CN 105085343A
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Abstract
A preparation method of a disulfide compound 3,3'-dithiodipropionic acid comprises the steps of: subjecting the raw materials of sodium hydrosulfide, acrylonitrile, iodine solution and acid to Michael addition, acidification, oxidation and hydrolysis; and recrystallizing and purifying to obtain the disulfide compound 3,3'-dithiodipropionic acid. Compared with the prior art, the method has the beneficial effects of safety, simpleness, green, environment-friendliness, simple technology, high yield and low production costs.
Description
Technical field
The present invention relates to a kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid.
Background technology
Disulfide compound 3,3'-dithiodipropionic acid is the important intermediate of preparation 3,3'-dithio dipropyl dimethyl phthalate, 3,3'-dithio dipropyl dimethyl phthalate is the intermediate of synthesis isothiazole ketone industrial fungicide, also can be used as nickel plating brightener and metal surface detergent simultaneously.
Patent US20120040418A1 describes and a kind of first prepares 2-cyano group sulfur alcohol with Sodium sulfhydrate, vinyl cyanide, sulfuric acid, chloroform for raw material; Prepare 3,3'-dithio dipropyl nitrile by iodine oxidation again, by column chromatography, crude product is purified; The preparation method of disulfide compound 3,3'-dithiodipropionic acid is obtained finally by cyan-hydrolysis enzymic hydrolysis.In this preparation method, souring agent is sulfuric acid, generates a large amount of sodium sulfate in reaction process, because sodium sulfate solubleness is lower, in last handling process, constantly there is sulfate crystal to separate out along with temperature reduces, aftertreatment is difficult to carry out in order, and in waste water, sodium sulphate content is higher, and environmental pollution is serious; Use chloroform as the extraction agent of 2-cyano group sulfur alcohol in this preparation method, because chloroform has anesthesia, carcinogenic possibility, serious to personal injury, environmental pollution; Purified by column chromatography to 3,3'-dithio dipropyl nitrile crude product, the time of purifying is long, and yield is lower, and production cost is high; Obtain 3,3'-dithiodipropionic acid by cyan-hydrolysis enzymic hydrolysis, because enzyme has the high feature of reactive behavior, not easily store, and enzyme is expensive, raw materials cost is higher, and this preparation method is not suitable for suitability for industrialized production.
Therefore explore a kind of simple to operate, personal injury, the preparation method of environmental pollution is lower, production cost is low disulfide compound 3,3'-dithiodipropionic acid has very important meaning.
Summary of the invention
The technical problem that the present invention mainly solves overcomes complex process in above-mentioned preparation method, serious to personal injury, environmental pollution, the problem that product yield is low, production cost is high, the disulfide compound 3 that a kind of safe, green, environmental protection, technique are simple, with low cost is provided, the preparation method of 3'-dithiodipropionic acid, its structure is as follows:
S
2（CH
2CH
2COOH）
2。
Disulfide compound 3 of the present invention, the preparation method of 3'-dithiodipropionic acid is Sodium sulfhydrate, vinyl cyanide, iodine solution, acid is raw material, successively by Michael addition, acidifying, oxidation, be hydrolyzed the crude product that three steps obtain disulfide compound, purifying finally by recrystallization obtains disulfide compound 3,3'-dithiodipropionic acid; Concrete preparation method is as follows:
A kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid, is characterized in that: preparation process is as follows:
A) 70% Sodium sulfhydrate in add water stirring and dissolving by the weight ratio of 1:0.9, at 35 ~ 40 DEG C, vinyl cyanide 1h is added drop-wise in sodium hydrosulfide by the mol ratio according to 1:1.15 ~ 1.3,2 ~ 3h is incubated at 35 ~ 40 DEG C, insulation terminates the rear mol ratio according to 1:1.75 ~ 2 and adds souring agent, the pH value of reaction solution is adjusted to after below 2.0, with hydrogen sulfide absorption liquid, secondary absorption is carried out to the hydrogen sulfide produced under negative pressure during acidifying, hydrogen sulfide is converted into Sodium sulfhydrate; Then add organic solvent according to the weight ratio of 1:0.2, extract 2 times, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
Reaction is followed the tracks of, the content of detection compound I by vapor-phase chromatography;
Wherein souring agent is the hydrochloric acid soln of 30%;
Hydrogen sulfide absorption liquid is the sodium hydroxide solution of 30%;
Organic solvent is toluene;
B) in chemical compounds I a) obtained, add water according to the weight ratio of 1:1.25, be cooled to 5 DEG C; At 5 ~ 25 DEG C, with 1h by compound Ι: iodine solution mol ratio is that the iodine solution of 1:0.5 ~ 0.6 is added drop-wise in the aqueous solution of chemical compounds I, slaking 1 ~ 2h at 5 ~ 25 DEG C, filter, with water cleaning, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) according to compound ii: sour mol ratio is that the ratio of 1:4 ~ 4.2 adds hydrolytic reagent in solid b) obtained, and is warming up to 100 ~ 115 DEG C, backflow 1 ~ 2h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
Wherein hydrolytic reagent to be massfraction be 30% hydrochloric acid soln;
D) target compound crude product III recrystallization solvent c) obtained is dissolved, obtain highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization;
Wherein recrystallization solvent is dehydrated alcohol.
Target compound by magnetic resonance detection product purity, and measures its fusing point.
The present invention strictly controls reaction conditions in three-step reaction process, and in step a) Michael addition reaction, controlling addition temperature is 35 ~ 40 DEG C, and reaction end is followed the tracks of vinyl cyanide disappearance with gas-chromatography and is as the criterion; Souring agent use hydrochloric acid, the sodium-chlor generated in reaction process reclaim, waste water recycling to production in, non-wastewater discharge pair in production process; Extracted by toluene intermediate I, toluene is minimum to personal injury, environmental pollution, and the use of extraction agent is safer.In step b) oxidizing reaction, controlled oxidization temperature is 5 ~ 25 DEG C, and reaction end is followed the tracks of chemical compounds I disappearance with gas-chromatography and is as the criterion.In step c) hydrolysis reaction, hydrolytic reagent uses hydrochloric acid, does not need to purify to second oxidation reaction product, shortens preparation time, improves the yield of intermediate II; Hydrochloric acid is cheap and easy to get, and easily preserves, and reduces and produces and storage cost; Be 100 ~ 115 DEG C by controlled hydrolysis temperature, ensure that intermediate II can be converted into 3,3'-dithio dipropyl acid crude completely, improve target compound yield, reduce production cost; By organic solvent recrystallization, 3,3'-dithio dipropyl acid crude is purified, ensure the purity of target product.
The invention has the beneficial effects as follows: the souring agent prepared selected by disulfide compound is hydrochloric acid, waste water recycling to production in, non-wastewater discharge in production; The extraction agent toluene low toxicity used, minimum to personal injury, environmental pollution; Intermediate is not needed to be purified by column chromatography, has saved the production time, improve the yield of intermediate; By using hydrolytic reagent hydrochloric acid to be hydrolyzed, reducing raw material and storage cost, improve the yield of target compound simultaneously, reduce production cost.
Embodiment
Embodiment 1
A kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid, comprises the following steps:
A) Sodium sulfhydrate of 48.1g-70% is added 43.5g water dissolution, at 35 DEG C, 31g vinyl cyanide 1h is added drop-wise in the Sodium sulfhydrate aqueous solution, 2h is incubated at 35 DEG C, the hydrochloric acid adding 125g-30% after insulation terminates carries out acidifying, the pH value of reaction solution is adjusted to after below 2.0, and the sodium hydroxide solution under negative pressure with alkali lye 30% during acidifying carries out secondary absorption to the hydrogen sulfide produced; Then extract 2 times with 50g toluene, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
By gas chromatographic detection chemical compounds I content, content is 98.5%
B) in chemical compounds I a) obtained, add water according to the weight ratio of 1:1.25, be cooled to 5 DEG C.At 5 DEG C, be added drop-wise in the aqueous solution of chemical compounds I with 1h by the iodine solution of 254mL-0.5mol/L, slaking 1h at 5 DEG C, filter, with water cleaning, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) in solid b) obtained, add the hydrochloric acid soln of 285g-30%, be warming up to 100 DEG C, backflow 2h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
D) target product crude product III anhydrous alcohol solution will c) obtained, obtains highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization.
Target compound yield is 56%, the target compound product purity by magnetic resonance detection, and without assorted peak on spectrogram, and determine fusing point, melting range is 152 ~ 153 DEG C.
Embodiment 2
A kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid, comprises the following steps:
A) Sodium sulfhydrate of 48.1g-70% is added 43.5g water dissolution, at 40 DEG C, 31g vinyl cyanide 1h is added drop-wise in the Sodium sulfhydrate aqueous solution, 2h is incubated at 40 DEG C, the hydrochloric acid adding 125g-30% after insulation terminates carries out acidifying, the pH value of reaction solution is adjusted to after below 2.0, and the sodium hydroxide solution under negative pressure with 30% during acidifying carries out secondary absorption to the hydrogen sulfide produced.Then use the hcl as extraction agent 2 times of 50g-30%, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
By passing through gas chromatographic detection chemical compounds I content, content is 99.3%;
B) in chemical compounds I a) obtained, add water according to the weight ratio of 1:1.25, at 25 DEG C, with 1h, the iodine solution of 254mL-0.5mol/L is added drop-wise in the aqueous solution of chemical compounds I, slaking 1h at 25 DEG C, filters, cleans with water, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) in solid b) obtained, add the hydrochloric acid soln of 285g-30%, be warming up to 115 DEG C, backflow 2h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
D) target product crude product III anhydrous alcohol solution will c) obtained, obtains highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization.
Target compound yield is 78%, the target compound product purity by magnetic resonance detection, and without assorted peak on spectrogram, and determine fusing point, melting range is 152 ~ 153 DEG C.
Embodiment 3
A kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid, comprises the following steps:
A) Sodium sulfhydrate of 60.8g-70% is added 43.5g water dissolution, at 40 DEG C, 31g vinyl cyanide 1h is added drop-wise in the Sodium sulfhydrate aqueous solution, 2h is incubated at 40 DEG C, the hydrochloric acid adding 142g-30% after insulation terminates carries out acidifying, the pH value of reaction solution is adjusted to after below 2.0, and the sodium hydroxide solution under negative pressure with 30% during acidifying carries out secondary absorption to the hydrogen sulfide produced.Then extract 2 times with 50g toluene, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
By passing through gas chromatographic detection chemical compounds I content, content is 95.8%;
B) in chemical compounds I a) obtained, add water according to the weight ratio of 1:1.25, at 25 DEG C, with 1h, the iodine solution of 235mL-0.5mol/L is added drop-wise in the aqueous solution of chemical compounds I, slaking 1h at 25 DEG C, filters, cleans with water, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) in solid b) obtained, add the hydrochloric acid soln of 299g-30%, be warming up to 115 DEG C, backflow 2h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
D) target compound crude product III anhydrous alcohol solution will c) obtained, obtains highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization.
Target compound yield is 47%, the target compound product purity by magnetic resonance detection, and spectrogram finds 3,3'-thio-2 acid is mixed peak, and determine fusing point, melting range is 152 ~ 155 DEG C.
Embodiment 4
A kind of preparation method of disulfide compound 3,3'-dithiodipropionic acid, comprises the following steps:
A) Sodium sulfhydrate of 48.1g-70% is added 43.5g water dissolution, at 40 DEG C, 31g vinyl cyanide 1h is added drop-wise in the Sodium sulfhydrate aqueous solution, 1h is incubated at 40 DEG C, the hydrochloric acid adding 125g-30% after insulation terminates carries out acidifying, the pH value of reaction solution is adjusted to after below 2.0, and the sodium hydroxide solution under negative pressure with alkali lye 30% during acidifying carries out secondary absorption to the hydrogen sulfide produced.Then extract 2 times with 50g toluene, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
By passing through gas chromatographic detection chemical compounds I content, content is 86.7%;
B) add water in chemical compounds I a) obtained, at 25 DEG C, be added drop-wise in the aqueous solution of chemical compounds I with 1h by the iodine solution of 254mL-0.5mol/L, slaking 1h at 25 DEG C, filter, with water cleaning, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) in solid b) obtained, add the hydrochloric acid soln of 285g-30%, be warming up to 115 DEG C, backflow 1h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
D) target compound crude product III anhydrous alcohol solution will c) obtained, obtains highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization.
Target compound yield is 28%, the target compound product purity by magnetic resonance detection, and spectrogram finds 3,3'-thio-2 acid is mixed peak, and determine fusing point, melting range is 138 ~ 150 DEG C.
Claims (1)
1. the preparation method of disulfide compound 3, a 3'-dithiodipropionic acid, is characterized in that: preparation process is as follows:
A) 70% Sodium sulfhydrate in add water stirring and dissolving by the weight ratio of 1:0.9, at 35 ~ 40 DEG C, vinyl cyanide 1h is added drop-wise in sodium hydrosulfide by the mol ratio according to 1:1.15 ~ 1.3,2 ~ 3h is incubated at 35 ~ 40 DEG C, insulation terminates the rear mol ratio according to 1:1.75 ~ 2 and adds souring agent, the pH value of reaction solution is adjusted to after below 2.0, with hydrogen sulfide absorption liquid, secondary absorption is carried out to the hydrogen sulfide produced under negative pressure during acidifying, hydrogen sulfide is converted into Sodium sulfhydrate; Then add organic solvent according to the weight ratio of 1:0.2, extract 2 times, merge organic phase, under reduced pressure concentrate, raffinate is carried out underpressure distillation under 45 ~ 48 DEG C/3torr, obtains chemical compounds I, its structural formula is as follows:
HSCH
2CH
2CN
Reaction is followed the tracks of, the content of detection compound I by vapor-phase chromatography;
Wherein souring agent is the hydrochloric acid soln of 30%;
Hydrogen sulfide absorption liquid is the sodium hydroxide solution of 30%;
Organic solvent is toluene;
B) in chemical compounds I a) obtained, add water according to the weight ratio of 1:1.25, be cooled to 5 DEG C; At 5 ~ 25 DEG C, with 1h by compound Ι: iodine solution mol ratio is that the iodine solution of 1:0.5 ~ 0.6 is added drop-wise in the aqueous solution of chemical compounds I, slaking 1 ~ 2h at 5 ~ 25 DEG C, filter, with water cleaning, obtain compound ii, its structural formula is as follows:
S
2(CH
2CH
2CN)
2
C) according to compound ii: sour mol ratio is that the ratio of 1:4 ~ 4.2 adds hydrolytic reagent in solid b) obtained, and is warming up to 100 ~ 115 DEG C, backflow 1 ~ 2h, lowers the temperature reaction solution, filters, washing filter cake, and obtain target compound crude product III, its structure is as follows:
S
2(CH
2CH
2COOH)
2
Wherein hydrolytic reagent to be massfraction be 30% hydrochloric acid soln;
D) target compound crude product III recrystallization solvent c) obtained is dissolved, obtain highly purified target compound disulfide compound 3,3'-dithiodipropionic acid by organic solvent recrystallization;
Wherein recrystallization solvent is dehydrated alcohol.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283107A (en) * | 2019-06-25 | 2019-09-27 | 山西其右建材科技有限公司 | A kind of inexpensive green production process of novel 3- sulfydryl propionitrile coproduction thiodipropionetrile |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3280163A (en) * | 1963-05-06 | 1966-10-18 | Phillips Petroleum Co | Production of mercapto-substituted nitriles |
| CN1793117A (en) * | 2005-12-20 | 2006-06-28 | 顾建荣 | Process for preparing 3-mercaptopropyl acid |
| CN102575273A (en) * | 2009-04-30 | 2012-07-11 | 三井化学株式会社 | Process for production of 3-mercaptopropionic acid or salt thereof |
-
2015
- 2015-09-10 CN CN201510569327.5A patent/CN105085343A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3280163A (en) * | 1963-05-06 | 1966-10-18 | Phillips Petroleum Co | Production of mercapto-substituted nitriles |
| CN1793117A (en) * | 2005-12-20 | 2006-06-28 | 顾建荣 | Process for preparing 3-mercaptopropyl acid |
| CN102575273A (en) * | 2009-04-30 | 2012-07-11 | 三井化学株式会社 | Process for production of 3-mercaptopropionic acid or salt thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283107A (en) * | 2019-06-25 | 2019-09-27 | 山西其右建材科技有限公司 | A kind of inexpensive green production process of novel 3- sulfydryl propionitrile coproduction thiodipropionetrile |
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