CN1042350A - N, the preparation method of N '-dimethyl-3,3 '-dithio dipropyl acidamide - Google Patents
N, the preparation method of N '-dimethyl-3,3 '-dithio dipropyl acidamide Download PDFInfo
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Abstract
The present invention is the synthetic intermediate N of sanitas 2-methyl 4-isothiazoline-3-ketone and 5-chloro-2-methyl-4-isothiazoline-3-ketone, the preparation method of N '-dimethyl-3,3 '-dithio dipropyl acidamide.It is to be reacted under the effect of ammonium sulfide solution and hydrochloric acid by methyl acrylate and sodium polysulphide, again through sodium sulfite aqueous solution handle obtain intermediate 3,3 '-dimethyl propionate of dithio, addings-aqueous methylamine solution direct reaction acquisition then.Prepare N with this method, N '-dimethyl-3,3 '-dithio dipropyl acidamide, technology is simple, and is easy to operate, and the yield height does not have environmental pollution, is easy to suitability for industrialized production.
Description
The invention belongs to thioamides synthetic technology in the sulfur chemistry.
N, N '-dimethyl-3,3 '-dithio dipropyl acidamide (II) are the synthetic precursors of sanitas 2-methyl-4-isothiazoline-3-ketone and 5-chloro-2-methyl-4-isothiazoline-3-ketone.
For synthesizing of compound (II), the contained method of EP95907 is to 3,3 '-toluene-methanol solution of dithio dipropyl acid esters (I) in feeding-methylamine gas, continuously stirring is 20 hours then, steam solvent and obtain impure crude product, behind the Virahol recrystallization, obtain elaboration (II) again.
For synthesizing of compound (I), at US3,769, the existing argumentation in 315, this method are to adopt hydrogen sulfide and sulphur and methyl acrylate reaction, generate the two methyl propionates of polythio, handle with sodium sulfite aqueous solution, obtain compound (I), its preparation route is as follows:
The method main drawback of above-mentioned synthetic compound (I) is:
This route is the solid, liquid, gas phase reaction, and the utilization ratio of hydrogen sulfide is low, and unreacted hydrogen sulfide is discharged by tail gas, the device that needs a cover absorbing hydrogen sulphide, not only uneconomical but also contaminate environment, the operator's of serious harm simultaneously health is difficult to use aborning.
The method main drawback of above-mentioned synthetic compound (II) is:
-methylamine gas absorbs not exclusively, not only wasted but also contaminate environment, need long-time the stirring during reaction, big energy-consuming, must remove unreacted-methylamine, toluene and methyl alcohol by underpressure distillation after the reaction, the compound of gained (II) crude product purity is very poor, must just can obtain the compound (II) of required purity with organic solvent Virahol periodic crystallisation.Also need reclaim solvent, complex operation, equipment complexity.
The objective of the invention is to improve operational path, reduce cost, reduce toxicity, be convenient to suitability for industrialized production and strengthen practicality.
The present invention adopts sodium polysulphide and hydrochloric acid and methyl acrylate to react in ammonium sulfide solution, generate the two methyl propionates of polythio earlier, handle with sodium sulfite aqueous solution again and obtain compound (I), allow then-direct and compound (I) reaction of aqueous methylamine solution, obtain compound (II).Its synthetic route is as follows:
Sodium polysulphide is the mixture that X=2-5 sulfur-bearing number does not wait
With sodium polysulphide and hydrochloric acid and methyl acrylate reaction, generate the two methyl propionates of polythio, handle the entire reaction obtain intermediate compound (I) with sodium sulfite aqueous solution again and carry out in liquid phase, temperature of reaction is-20-30 ℃, optimal reaction temperature is-and 10-20 ℃; Reaction times is more than 0.25 hour, and optimum reacting time is 0.25-10 hour; The mol ratio of methyl acrylate sodium polysulphide is 1: 0.3-2; The mol ratio of methyl acrylate and hydrochloric acid is 1: 0.7-1.8.When the feed proportioning mol ratio is a methyl acrylate: sodium polysulphide: hydrochloric acid=1: 0.5-0.8: during 0.8-1.3, utilization ratio of raw materials is for the highest, and is most economical.
When-aqueous methylamine solution directly reacted with compound (I), not with an organic solvent, (I) do not need drying, and it is also harmless both just to have contained more moisture content.Temperature of reaction is at-10-45 ℃, and optimum temps is 5-35 ℃.Reaction does not need long-time stirring, only needs general-aqueous methylamine solution to splash in the compound (I).Be stirred to after dripping off to place after the crystallization and get final product.Reaction and placement total time are 0.5-72 hour.Reactant (I) and-mol ratio of methylamine is 1: can make compound (II) between the 1.5-60, but optimum proportion is: (I) :-methylamine=1: 2.0-3.5.
Its advantage of method that the present invention prepares compound (II) and intermediate (I) thereof is:
1. replace hypertoxic gas vulcanization hydrogen with sodium polysulphide and hydrochloric acid, reduced environmental pollution, ensured operator's health.
2. become phase reaction and be homogeneous reaction, improved utilization ratio of raw materials, increased yield.
3. equipment is simple, and is easy to operate, uses aborning easily.
4. the compound that makes with this method (II) purity is very high, generally can be directly used in preparation 5-chloro-2-methyl-4-isothiazoline-3-ketone and 2-methyl-4-isothiazoline-3-ketone without recrystallization.Both made and contained small amount of impurities, also a water recrystallization once can be removed.
Example 1
In 1000 milliliters of there-necked flasks, add 460.3 gram sodium polysulphide and 96 gram ammonium sulfide solutions, after the cooling, stir and dripped 135.6 gram vinylformic acid formicester and 103 milliliters of hydrochloric acid in following minute two the road simultaneously, maintain the temperature at 0-5 ℃, after dropwising, keep low temperature to continue to stir 1.5 hours.
Tell organic phase, with 750 milliliters of 1M S-WATs, 50 ℃ of thermal treatment 3 hours.Put and tell organic phase after cold with 2 * 150 milliliters of washing secondaries, tell organic layer after leaving standstill and be 3,3 '-dimethyl propionate of dithio (I).
Must measure: 174.5 grams; Content: 95.21%; Yield: 93.03%.
Digest compound (I) to prepared 174.5 and place the there-necked flask that agitator is housed, stir down, temperature 20 ℃ splash into 36%-aqueous methylamine solution 125.9 gram, being stirred to crystallization produces, place after 72 hours, go into refrigerator and placed 4 hours for 10 ℃, filter with the clean mother liquor of 3 * 100 ml waters flushing decompression filter, weigh behind the crystallizing and drying 117.5 the gram, m.p 113.5-115 ℃.
Crude product is behind the water recrystallization: m.p 114.5-115.5 ℃.
Example 2
In 1000 milliliters of there-necked flasks, add 411.6 gram sodium polysulphide and 75 gram ammonium sulfide solutions, after the cooling, stir and dripped 135.6 gram methyl acrylate and 167 milliliters of hydrochloric acid in following minute two the road simultaneously, maintain the temperature at 5-10 ℃, after dropwising, keep low temperature to continue to stir 1 hour.
Tell organic phase, with 750 milliliters of 1M S-WATs, 50 ℃ of thermal treatment 3 hours.Put and tell organic phase after cold with 2 * 150 milliliters of washing secondaries.Tell organic layer after leaving standstill, be 3,3 '-dimethyl propionate of dithio.
Must measure 170 grams, content 95.78%, yield 91.16%.
Get compound (I) 168 gram, place the there-necked flask that stirring is housed, stir following 20 ℃ splash into 36%-aqueous methylamine solution 197.9 grams, be stirred to crystallization and produced, placed 5 hours, go into 3 ℃ of placements of refrigerator 2 hours.Filter 23 * 100 ml waters flushing, the clean mother liquor of decompression filter, 116.5 grams of weighing behind the crystallizing and drying.m.p 113.5-115℃。
Crude product is behind the water recrystallization: m.p 114.5-115.5 ℃.
Example 3
In 1000 milliliters of there-necked flasks, add 288.4 gram sodium polysulphide and 57 gram ammonium sulfide solutions, after the cooling, stir and dripped 135.6 gram methyl acrylate and 125 milliliters of hydrochloric acid in following minute two the road simultaneously, maintain the temperature at-5-0 ℃, after dropwising, keep low temperature to continue to stir 0.5 hour.
Tell organic phase, with 750 milliliters of 1M S-WATs, 50 ℃ of thermal treatment 3 hours is put the cold organic phase of telling and is washed secondaries with 2 * 150 milliliters, tell organic layer after leaving standstill and be 3,3 '-dimethyl propionate of dithio.
Must heavily be 176 grams, content 94.59%, yield 93.22%.
Get the compound (I) that makes 168 grams, place the there-necked flask that stirring is housed, stir following 20 ℃ splash into 36%-aqueous methylamine solution 197.9 grams, be stirred to crystallization and produced, placed 5 hours, go into 3 ℃ of placements of refrigerator 2 hours.Filter 23 * clean the mother liquor of 100 ml waters flushing decompression filter, 116.5 grams of weighing behind the crystallizing and drying.m.p 113.5-115℃。
Crude product is behind the water recrystallization: m.p 114.5-115.5 ℃.
Check to be a spot with the thin layer folding.
Ultimate analysis: calculated value: C:40.65 H:6.84
N：11.85 S：27.13
Analytical value: C:40.69 H:6.82
N：11.92 S：26.71
Nuclear magnetic resonance spectroscopy: solvent: CDCl
3
Accompanying drawing is: N, N '-dimethyl-3,3 '-dithio dipropyl acidamide
EP95907 prepares the route block diagram.
Claims (7)
1, a kind of N, N '-dimethyl-3,3 '-preparation method of dithio dipropyl acidamide (II), it is characterized in that sodium polysulphide and hydrochloric acid and methyl acrylate react under the ammonium sulfide solution effects, generate earlier the two methyl propionates of polythio, again with sodium sulfite aqueous solution handle obtain compound 3,3 '-dithio dipropyl acid esters (I), allow then-direct and compound (I) reaction of aqueous methylamine solution, obtain compound (II).Its synthetic route is as follows:
Sodium polysulphide is the mixture that X=2-5 sulfur-bearing number does not wait.
2, preparation method according to claim 1 is characterized in that the mol ratio for preparing compound (I) desired raw material dosage is:
Methyl acrylate: sodium polysulphide: hydrochloric acid=1: 0.3-2: 0.7-1.8
Optimum ratio, methyl acrylate: sodium polysulphide: hydrochloric acid=
1∶0.5-0.8∶0.8-1.3;
3, preparation method according to claim 1 is characterized in that preparing the required temperature of compound (I) and is-20 ℃-30 ℃, and optimum temps is-10-20 ℃.
4, preparation method according to claim 1, it is characterized in that preparing the required time of compound (I) is more than 0.25 hour, Best Times is 0.25-10 hour.
5, preparation method according to claim 1, the mol ratio that it is characterized in that preparing compound (II) required compound (I) and-methylamine is (I) :-methylamine=1: 1.5-60; Optimum proportion is (I) :-methylamine=1: 2.0-3.5.
6, preparation method according to claim 1, the temperature of reaction that it is characterized in that preparing compound (II) is-10-45 ℃, optimal reaction temperature is 5-35 ℃.
7, preparation method according to claim 1, the reaction times and the storage period that it is characterized in that preparing compound (II) are 0.5-72 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 88107418 CN1024546C (en) | 1988-10-31 | 1988-10-31 | Production of N,N'-dimethyl,3,3'-dithiodipropionamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 88107418 CN1024546C (en) | 1988-10-31 | 1988-10-31 | Production of N,N'-dimethyl,3,3'-dithiodipropionamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1042350A true CN1042350A (en) | 1990-05-23 |
| CN1024546C CN1024546C (en) | 1994-05-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 88107418 Expired - Fee Related CN1024546C (en) | 1988-10-31 | 1988-10-31 | Production of N,N'-dimethyl,3,3'-dithiodipropionamide |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006037274A1 (en) * | 2004-10-10 | 2006-04-13 | Ocean University Of China | Alkoxypropyl isothiazolinone and preparation method and use thereof |
| CN1709868B (en) * | 2005-04-18 | 2010-05-05 | 中国海洋大学 | Dithio dipropyl acidamide, and its preparing method and use |
| CN102180819A (en) * | 2011-04-08 | 2011-09-14 | 李绍通 | 3,3'New process for synthesizing 3,3'-dithio-bispropionate |
| CN102791685A (en) * | 2009-12-16 | 2012-11-21 | Sk化学株式会社 | Method for preparing N,N'-dialkyl-3,3'-dithiodipropionamides |
-
1988
- 1988-10-31 CN CN 88107418 patent/CN1024546C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006037274A1 (en) * | 2004-10-10 | 2006-04-13 | Ocean University Of China | Alkoxypropyl isothiazolinone and preparation method and use thereof |
| JP2008515820A (en) * | 2004-10-10 | 2008-05-15 | 中国海洋大学 | Alkoxypropylisothiazolinone, and its production and use |
| US7442240B2 (en) | 2004-10-10 | 2008-10-28 | Ocean University Of China | Alkoxylpropylisothiazolinone and preparation method and use thereof |
| JP4789950B2 (en) * | 2004-10-10 | 2011-10-12 | 中国海洋大学 | Alkoxypropylisothiazolinone, and its production and use |
| CN1709868B (en) * | 2005-04-18 | 2010-05-05 | 中国海洋大学 | Dithio dipropyl acidamide, and its preparing method and use |
| CN102791685A (en) * | 2009-12-16 | 2012-11-21 | Sk化学株式会社 | Method for preparing N,N'-dialkyl-3,3'-dithiodipropionamides |
| CN102180819A (en) * | 2011-04-08 | 2011-09-14 | 李绍通 | 3,3'New process for synthesizing 3,3'-dithio-bispropionate |
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| Publication number | Publication date |
|---|---|
| CN1024546C (en) | 1994-05-18 |
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