CN108530380B - Synthesis method of N-methyl-1, 2-benzisothiazolin-3-one - Google Patents
Synthesis method of N-methyl-1, 2-benzisothiazolin-3-one Download PDFInfo
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- CN108530380B CN108530380B CN201810397189.0A CN201810397189A CN108530380B CN 108530380 B CN108530380 B CN 108530380B CN 201810397189 A CN201810397189 A CN 201810397189A CN 108530380 B CN108530380 B CN 108530380B
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- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
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Abstract
The invention provides a synthetic method of N-methyl-1, 2-benzisothiazolin-3-ketone, which comprises the following steps: step one, introducing methyl chloride into a first system formed by 1, 2-benzisothiazolin-3-one, liquid caustic soda and water, stopping introducing the methyl chloride until the content of the 1, 2-benzisothiazolin-3-one in the mixture is less than 1%, cooling, standing and layering, and collecting an upper organic layer; step two, collecting an upper water layer, adding 1, 2-benzisothiazole-3-ketone, caustic soda flakes and a composite catalyst into the upper water layer to form a second system, heating, introducing chloromethane until the content of the 1, 2-benzisothiazole-3-ketone is below 1%, cooling, standing and layering, and distilling an upper organic layer under reduced pressure; collecting the lower aqueous layer of the second system and repeating the second step. The method has the advantages of fewer reaction steps and shorter route; the raw materials are cheap and easy to obtain, and the cost is reduced; the raw materials and the byproducts of the invention have no odor or less odor, and are relatively friendly to the environment; the invention avoids generating a large amount of waste liquid to reduce the environmental protection pressure of enterprises.
Description
Technical Field
The invention belongs to a synthesis method, and particularly relates to a synthesis method of N-methyl-1, 2-benzisothiazolin-3-one.
Background
The prior art mainly comprises two processes, wherein one process takes 2-methylthiobenzoic acid as a raw material and prepares N-methyl-1, 2-benzisothiazolin-3-ketone through acylation, methylamino and chlorination cyclization; the other is N-methyl-1, 2-benzisothiazolin-3-one prepared with 1, 2-benzisothiazolin-3-one sodium salt as material and methyl reagent dimethyl carbonate, dimethyl sulfate, etc. in aprotic polar solvent DMF, DMSO, etc.
The first raw material in the prior art has various and expensive types, long process route, complex working procedures, high difficulty and low product yield.
In the second method in the prior art, an aprotic polar solvent is used as a medium, the solvent cannot be recycled due to the influence of impurities, a large amount of waste liquid is generated, and in actual production, the organic solvent has certain safety risk and the yield of the product is low.
Disclosure of Invention
The invention provides a synthesis method of N-methyl-1, 2-benzisothiazolin-3-one, which has fewer reaction steps and a shorter route.
According to one aspect of the present invention, there is provided a method for synthesizing N-methyl-1, 2-benzisothiazolin-3-one, comprising the steps of:
step one, introducing methyl chloride into a first system formed by 1, 2-benzisothiazolin-3-one, liquid caustic soda and water, stopping introducing the methyl chloride until the content of the 1, 2-benzisothiazolin-3-one in the mixture is less than 1%, cooling, standing and layering, and collecting an upper organic layer, and performing reduced pressure distillation to obtain N-methyl-1, 2-benzisothiazolin-3-one with the content of more than 99%;
step two, collecting an upper water layer, adding 1, 2-benzisothiazolin-3-one, caustic soda flakes and a composite catalyst into the upper water layer to form a second system, heating, introducing methyl chloride until the content of the 1, 2-benzisothiazolin-3-one is below 1%, cooling, standing and layering, and distilling an upper organic layer under reduced pressure to obtain N-methyl-1, 2-benzisothiazolin-3-one with the content of more than 99%;
and collecting the lower water layer of the second system, filtering and repeating the step two.
In some embodiments, the first step is: adding 1mol of 1, 2-benzisothiazolin-3-one and 1mol of liquid alkali into 400g of water, stirring and dissolving to form a first system, adding 6% of composite catalyst into the first system, heating the first system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting 1, 2-benzisothiazolin-3-one residue below 1% by high performance liquid chromatography, stopping introducing chloromethane, cooling to 30-40 ℃, standing and layering, collecting a lower water layer, distilling an upper organic layer under reduced pressure to obtain N-methyl-1, 2-benzisothiazolin-3-one, wherein the yield is 90-95%, and the content is more than 99%;
in some embodiments, the second step is: adding 1mol of 1, 2-benzisothiazolin-3-one, 1mol of caustic soda and 1% of composite catalyst into the collected lower water layer to form a second system, heating the second system to 80-100 ℃, introducing methyl chloride, leading the solution to become turbid, detecting that the 1, 2-benzisothiazolin-3-one is remained below 1% by high performance liquid chromatography, stopping introducing methyl chloride, cooling to 30-40 ℃, standing for layering, separating out sodium chloride in the lower water layer, filtering, collecting for reuse, distilling the upper organic layer under reduced pressure to obtain the N-methyl-1, 2-benzisothiazolin-3-one, wherein the yield is 95-98%, and the content is more than 99%;
in some embodiments, the composite catalyst consists of a halogenated salt and a phase transfer catalyst, the mass ratio of the halogenated salt to the phase transfer catalyst is 1:1, the halogenated salt is selected from sodium iodide, potassium iodide or sodium bromide, and the phase transfer catalyst is selected from tetrabutylammonium bromide or benzyltriethylammonium chloride.
In some embodiments, the reaction equation is:
the beneficial effects are as follows: the method has the advantages of fewer reaction steps and shorter route; the raw materials are cheap and easy to obtain, and the cost is reduced; the raw materials and the byproducts of the invention have no odor or less odor, and are relatively friendly to the environment; the invention avoids generating a large amount of waste liquid to reduce the environmental protection pressure of enterprises.
Detailed Description
The present invention will be further described with reference to the following examples.
A synthetic method of N-methyl-1, 2-benzisothiazolin-3-ketone comprises the following steps: step one, introducing methyl chloride into a first system formed by 1, 2-benzisothiazolin-3-one, liquid caustic soda and water, stopping introducing the methyl chloride until the content of the 1, 2-benzisothiazolin-3-one in the mixture is less than 1%, cooling, standing, layering, collecting an upper organic layer, and distilling under reduced pressure to obtain the N-methyl-1, 2-benzisothiazolin-3-one with the content of more than 99%. The method specifically comprises the following steps: adding 1mol of 1, 2-benzisothiazolin-3-one (BIT) and 1mol of liquid alkali into 400g of water, stirring and dissolving to form a first system, adding 6% of a composite catalyst into the first system, wherein the composite catalyst consists of a halogenated salt and a phase transfer catalyst, the mass ratio of the halogenated salt is 1:1, the halogenated salt is selected from sodium iodide, potassium iodide or sodium bromide, the phase transfer catalyst is selected from tetrabutylammonium bromide or benzyltriethylammonium chloride, heating the first system to 80-100 ℃, introducing methyl chloride, enabling the solution to become turbid, and stopping introducing the methyl chloride and cooling when the BIT is detected to be below 1% by High Performance Liquid Chromatography (HPLC); cooling to 30-40 deg.C, standing for layering, collecting lower water layer, and distilling upper organic layer under reduced pressure to obtain N-methyl-1, 2-benzisothiazolin-3-one (MBIT), with yield of 90-95% and content of more than 99%;
and step two, collecting the upper water layer, adding 1, 2-benzisothiazolin-3-one, caustic soda flakes and a composite catalyst into the upper water layer to form a second system, heating the second system, introducing chloromethane until the content of the 1, 2-benzisothiazolin-3-one is less than 1%, cooling, standing and layering the mixture, and distilling the upper organic layer under reduced pressure to obtain the N-methyl-1, 2-benzisothiazolin-3-one with the content of more than 99%. The method specifically comprises the following steps: adding 1mol of BIT, 1mol of caustic soda and 1% of composite catalyst into the collected lower water layer to form a second system, heating the second system to 80-100 ℃, introducing methyl chloride, leading the solution to become turbid, detecting BIT residue below 1% by HPLC, stopping introducing methyl chloride, cooling to 30-40 ℃, standing for layering, separating out sodium chloride in the lower water layer, filtering, collecting for reuse, and distilling the upper organic layer under reduced pressure to obtain MBIT, wherein the yield is 95-98%, and the content is more than 99%;
the collected lower aqueous layer was filtered and the above procedure was repeated.
The reaction equation is:
example one:
adding 151g of BIT and 125g of 32% liquid caustic soda into 400g of water, stirring for dissolving, adding 4.5g of potassium iodide and 4.5g of benzyltriethylammonium chloride composite catalyst into the system, heating the system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting by HPLC, stopping introducing chloromethane when the BIT is below 1%, cooling to 30-40 ℃, standing for layering, collecting the lower water layer for reuse, and distilling the upper organic layer under reduced pressure to obtain 154g of MBIT, wherein the yield is 93.4%, and the content is 99.1%.
Adding 151g of BIT and 40g of caustic soda flakes into the collected water layer, stirring for dissolving, adding 0.8g of potassium iodide and 0.8g of benzyltriethylammonium chloride composite catalyst into the system, heating the system to 80-100 ℃, introducing methyl chloride, leading the solution to become turbid, detecting by HPLC (high performance liquid chromatography), stopping introducing methyl chloride, cooling to 30-40 ℃, standing for layering, separating out partial sodium chloride from the lower water layer, filtering, collecting for reuse, and distilling the upper organic layer under reduced pressure to obtain 161g of MBIT, wherein the yield is 97.6%, and the content is 99.2%.
Example two:
adding 151g of BIT and 125g of 32% liquid caustic soda into 400g of water, stirring for dissolving, adding 4.5g of sodium iodide and 4.5g of tetrabutylammonium bromide composite catalyst into the system, heating the system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting by HPLC (high performance liquid chromatography), stopping introducing chloromethane, cooling to 30-40 ℃, standing for layering, collecting a lower water layer for reuse, and distilling an upper organic layer under reduced pressure to obtain 152g of MBIT, wherein the yield is 92.5%, and the content is 99.0%.
Adding 151g of BIT and 40g of caustic soda flakes into the collected water layer in the second embodiment, stirring for dissolving, adding 0.8g of sodium iodide and 0.8g of tetrabutylammonium bromide composite catalyst into the system, heating the system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting by HPLC (high performance liquid chromatography), stopping introducing the BIT below 1%, cooling to 30-40 ℃, standing for layering, separating out part of sodium chloride in the lower water layer, filtering, collecting for use, and distilling the upper organic layer under reduced pressure to obtain 159g of MBIT, wherein the yield is 96.4%, and the content is 99.1%.
Example three:
adding 151g of BIT and 125g of 32% liquid caustic soda into 400g of water, stirring for dissolving, adding 4.5g of potassium bromide and 4.5g of benzyltriethylammonium chloride composite catalyst into the system, heating the system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting by HPLC, stopping introducing chloromethane when the BIT is below 1%, cooling to 30-40 ℃, standing for layering, collecting the lower water layer for reuse, and distilling the upper organic layer under reduced pressure to obtain 149g of MBIT, wherein the yield is 90.3%, and the content is 99.0%.
Adding 151g of BIT and 40g of caustic soda flakes into the collected water layer in the third embodiment, stirring for dissolving, adding 0.8g of potassium bromide and 0.8g of benzyltriethylammonium chloride composite catalyst into the system, heating the system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting by HPLC (high performance liquid chromatography), stopping introducing the BIT below 1%, cooling to 30-40 ℃, standing for layering, separating out part of sodium chloride in the lower water layer, filtering, collecting for use, and distilling the upper organic layer under reduced pressure to obtain 157g of MBIT, wherein the yield is 95.2%, and the content is 99.0%.
What has been described above are merely some embodiments of the present invention. It will be apparent to those skilled in the art that various changes and modifications can be made without departing from the inventive concept thereof, and these changes and modifications can be made without departing from the spirit and scope of the invention.
Claims (2)
1. A synthetic method of N-methyl-1, 2-benzisothiazolin-3-ketone is characterized by comprising the following steps:
the method comprises the following steps: adding 1mol of 1, 2-benzisothiazolin-3-one and 1mol of liquid alkali into 400g of water, stirring and dissolving to form a first system, adding 6% of composite catalyst into the first system, heating the first system to 80-100 ℃, introducing chloromethane, leading the solution to become turbid, detecting 1, 2-benzisothiazolin-3-one residue below 1% by high performance liquid chromatography, stopping introducing chloromethane, cooling to 30-40 ℃, standing and layering, collecting a lower water layer, distilling an upper organic layer under reduced pressure to obtain N-methyl-1, 2-benzisothiazolin-3-one, wherein the yield is 90-95%, and the content is more than 99%;
adding 1, 2-benzisothiazolin-3-one, caustic soda flakes and a composite catalyst into the collected lower water layer to form a second system, heating, introducing methyl chloride until the content of the 1, 2-benzisothiazolin-3-one is below 1%, cooling, standing and layering, and distilling the upper organic layer under reduced pressure to obtain N-methyl-1, 2-benzisothiazolin-3-one with the content of more than 99%;
collecting the lower water layer of the second system, filtering and repeating the second step;
the composite catalyst consists of halogenated salt and a phase transfer catalyst, the mass ratio of the halogenated salt to the phase transfer catalyst is 1:1, the halogenated salt is selected from sodium iodide, potassium iodide or sodium bromide, and the phase transfer catalyst is selected from tetrabutylammonium bromide or benzyltriethylammonium chloride.
2. The method for synthesizing N-methyl-1, 2-benzisothiazolin-3-one according to claim 1, wherein the second step is: adding 1mol of 1, 2-benzisothiazolin-3-one, 1mol of caustic soda and 1% of composite catalyst into the collected lower water layer to form a second system, heating the second system to 80-100 ℃, introducing methyl chloride, leading the solution to become turbid, detecting that the 1, 2-benzisothiazolin-3-one is remained below 1% by high performance liquid chromatography, stopping introducing methyl chloride, cooling to 30-40 ℃, standing for layering, separating out sodium chloride in the lower water layer, filtering, collecting for reuse, distilling the upper organic layer under reduced pressure to obtain the N-methyl-1, 2-benzisothiazolin-3-one, wherein the yield is 95-98%, and the content is more than 99%.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103694194A (en) * | 2014-01-04 | 2014-04-02 | 寿光新泰精细化工有限公司 | Synthesis method of 2-methyl-1, 2-benzisothiazolin-3-ketone |
| WO2015106959A1 (en) * | 2014-01-16 | 2015-07-23 | Thor Gmbh | Method for producing n-alkyl-1,2-benzisothiazolin-3-ones |
| CN105593218A (en) * | 2013-09-25 | 2016-05-18 | 泰坦化工有限公司 | Process for preparing benzisothiazolinones |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105593218A (en) * | 2013-09-25 | 2016-05-18 | 泰坦化工有限公司 | Process for preparing benzisothiazolinones |
| CN103694194A (en) * | 2014-01-04 | 2014-04-02 | 寿光新泰精细化工有限公司 | Synthesis method of 2-methyl-1, 2-benzisothiazolin-3-ketone |
| WO2015106959A1 (en) * | 2014-01-16 | 2015-07-23 | Thor Gmbh | Method for producing n-alkyl-1,2-benzisothiazolin-3-ones |
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