CN111574472A - Synthesis method of 1, 2-benzisothiazolin-3-ketone compound - Google Patents
Synthesis method of 1, 2-benzisothiazolin-3-ketone compound Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 1, 2-benzisothiazolin-3-ketone compounds, belonging to the field of chemical synthesis. 2-sulfenyl substituted benzoic acid extracted from BIT process waste water is used as a starting material, and the 1, 2-benzisothiazolin-3-ketone compound is synthesized through acyl chlorination, amidation and cyclization reactions. The method disclosed by the invention has the advantages of mild reaction conditions, simplicity and convenience in operation, strong practicability, less wastewater, high product purity and the like, and is suitable for the requirement of large-scale industrial production. The technical scheme provided by the invention provides a feasible method for resource utilization of the wastewater extract generated in the BIT production process and preparation of the 1, 2-benzisothiazolin-3-one compound.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a synthesis method of a 1, 2-benzisothiazolin-3-one compound.
Background
The industrial bactericide is a preparation for killing or inhibiting the growth of microorganisms in the industrial field, and bactericides, bacteriostats, preservatives, mildewcides, algicides and the like used in industry are all called industrial bactericides. The 1, 2-benzisothiazolin-3-one compound is a novel high-efficiency industrial bactericide, and has the characteristics of no halogen, no need of metal ion stability, stability in a pH range of 2-12, high temperature resistance, low toxicity and the like. The 1, 2-benzisothiazolin-3-ketone compound has important functions of effectively preventing the diffusion and the propagation of bacteria, avoiding and reducing the immunity reduction caused by bacterial infection and effectively removing the bacteria, and plays an important role in the normal production and life of people. Therefore, the development of a new synthetic method for industrially producing the 1, 2-benzisothiazolin-3-one compound is of great significance.
Patent CN103694194 reports a synthesis method of 2-methyl-1, 2-benzisothiazolin-3-one, which comprises the steps of taking o-methylthiobenzoic acid as a raw material, carrying out thionyl chloride chlorination reaction and methylamine amination reaction, finally introducing chlorine gas or adding liquid bromine for cyclization reaction, and distilling to obtain the 2-methyl-1, 2-benzisothiazolin-3-one with the purity of 98%, wherein the yield is 67-77%. The method uses thionyl chloride and chlorine or liquid bromine as raw materials, the raw materials are extremely toxic, and a large amount of hydrogen chloride and sulfur dioxide waste gas generated in the reaction process needs to be treated. Patent US8884024 reports a method for synthesizing 2-methyl-1, 2-benzisothiazolin-3-one from BIT as a raw material, wherein dimethyl sulfate is dropwise added to BIT lithium salt in butanone as a solvent to obtain a mixture of 2-methyl-1, 2-benzisothiazolin-3-one and 3-methoxy-1, 2-benzisothiazolin. The method has the defects of poor selectivity during the N-alkylation reaction, higher raw material cost and limited industrial application.
In the process of producing 1, 2-benzisothiazolin-3-one (BIT) by a chlorine chlorination method, a large amount of wastewater with high salt and high organic matters which are difficult to treat is generated, and the harmless treatment of the wastewater becomes the problem which is mainly solved by BIT production enterprises, which directly determines whether the production can be normally carried out.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for synthesizing the 1, 2-benzisothiazolin-3-one compound, which has the advantages of low cost, high yield and good quality, is suitable for industrial production of the 1, 2-benzisothiazolin-3-one compound, and provides a feasible method for resource utilization of a wastewater extract generated in the BIT production process and preparation of the 1, 2-benzisothiazolin-3-one compound.
In order to achieve the purpose, the invention adopts the following technical scheme:
the 1, 2-benzisothiazolin-3-one compound has the following structural characteristics:
wherein R is2Represents hydrogen, alkyl, aryl; the alkyl group comprises straight chain alkyl and substituted alkyl with the carbon number of 1-8, branched chain alkyl and substituted alkyl, and cycloalkyl with the carbon number of 3-6 and substituted cycloalkyl, and the substituent on the alkyl group comprises chlorine, bromine, methyl, ethyl, methoxy and ethoxy; the aryl group comprises phenyl, substituted phenyl, benzyl and substituted benzyl, and the substituent group on the aryl group comprises chlorine, bromine, hydroxyl, methyl, ethyl, isopropyl, tert-butyl, methoxyl and ethoxyl.
In order to obtain the compounds with the main structure of 1, 2-benzisothiazolin-3-one, the following synthetic route is designed to prepare the compounds based on o-methylthiobenzoic acid and o-dithiodibenzoic acid extracted from BIT production wastewater:
the synthetic route has three steps of reactions, namely acyl chlorination, amidation and cyclization. The raw materials used in the route are o-methylthiobenzoic acid and o-dithiodibenzoic acid, and are obtained from the production wastewater of BIT;
(1) acyl chlorination reaction: the method comprises the following steps of (1) reacting o-methylthiobenzoic acid or o-dithiodibenzoic acid serving as a raw material with trichloromethyl chloroformate or bis (trichloromethyl) carbonate to generate o-methylthiobenzoyl chloride or o-dithiodibenzoyl chloride: in the step, the molar ratio of the o-methylthiobenzoic acid to the trichloromethyl chloroformate is 1: 0.5 to 2.5, preferably 1: 0.5 to 1.0; the molar ratio of the o-dithiodibenzoic acid to the trichloromethyl chloroformate is 1: 1.0 to 5.0, preferably 1: 1.0 to 2.0; the molar ratio of o-methylthiobenzoic acid to bis (trichloromethyl) carbonate is 1: 0.33 to 1.7, preferably 1: 0.35 to 0.7; the molar ratio of ortho-dithiodibenzoic acid to bis (trichloromethyl) carbonate is 1: 0.66-3.4, preferably 1: 0.7 to 1.4. The solvent used in the reaction is one or more of dichloromethane, dichloroethane, trichloromethane, tetrachloroethane, N-dimethylformamide, N-dimethylacetamide, toluene, xylene, chlorobenzene, dichlorobenzene and the like, and the reaction temperature ranges from-5 ℃ to 130 ℃, preferably 30 ℃ to 80 ℃;
(2) amidation reaction: amidating o-methylthio benzoyl chloride or o-dithio dibenzoyl chloride with primary amine containing different substituents to obtain o-methylthio benzamide or o-dithio dibenzoyl amide containing different substituents. In this step, the molar ratio of o-methylthiobenzoyl chloride to primary amine is 1: 1.0-3.5, preferably 1: 1.1-2.5; the molar ratio of the o-dithiodibenzoyl chloride to the primary amine is 1: 2.0 to 7.0, preferably 1: 2.2 to 4.5. The solvent used in the reaction is one or more of dichloromethane, dichloroethane, tetrachloroethane, tetrahydrofuran, methyltetrahydrofuran, dioxane and the like, and the reaction temperature ranges from-20 ℃ to 60 ℃, preferably from-10 ℃ to 30 ℃;
(3) cyclization reaction: n-alkyl-o-methylthiobenzamide or N-alkyl-o-dithio-benzamide containing different substituents is subjected to cyclization reaction under the action of halide positive ions to synthesize the 2-alkyl-1, 2-benzisothiazolin-3-one compound. In this step, the molar ratio of N-alkyl-o-methylthiobenzamide to halide cation of different substituents is 1: 0.6-2.8, preferably 1: 0.9 to 1.6; the molar ratio of N-alkyl-o-dithiodibenzoyl amide to halocation is 1: 1.2-5.6, preferably 1: 1.8 to 3.2. The solvent used in the reaction is one or more of dichloromethane, dichloroethane, tetrachloroethylene, tetrachloroethane and the like. The halide positive ions are one or more of chloride positive ions, bromide positive ions and iodide positive ions, the positive ion providing reagent is one or more of N-chlorosuccinimide, N-chlorophthalimide, N-bromosuccinimide, N-bromophthalimide, N-iodosuccinimide, N-iodophthalimide, 1, 3-dichloro-5, 5-dimethylhydantoin, 1, 3-dibromo-5, 5-dimethylhydantoin, 1, 3-diiodo-5, 5-dimethylhydantoin, trichloroisocyanuric acid, chlorobromoisocyanuric acid and the like, and the reaction temperature ranges from minus 10 ℃ to 140 ℃, and is preferably 35 ℃ to 70 ℃.
Compared with the prior art, the invention has the following beneficial effects:
the invention effectively realizes the resource recycling of the BIT production wastewater extract, and the synthesis method has the advantages of mild reaction conditions, simple and convenient operation, strong practicability, less wastewater, high product purity and the like, and is suitable for the requirement of large-scale industrial production. The technical scheme provided by the invention provides a feasible method for resource utilization of the wastewater extract generated in the BIT production process and preparation of the 1, 2-benzisothiazolin-3-one compound.
Drawings
FIG. 1 is a liquid chromatogram of 1, 2-benzisothiazolin-3-one standard (HPLC purity 100%) from example 6.
FIG. 2 is a liquid chromatogram of the experimental 1, 2-benzisothiazolin-3-one of example 6 (HPLC purity 99.9%).
FIG. 3 is a liquid chromatogram of 2-n-butyl-1, 2-benzisothiazolin-3-one standard (HPLC purity 100%) from example 8.
FIG. 4 is a liquid chromatogram of 2-n-butyl-1, 2-benzisothiazolin-3-one sample from example 8 (HPLC purity 99.3%).
Detailed Description
Comparative example 1
The o-methylthiobenzoyl chloride is prepared as follows:
adding 33.6g of o-methylthiobenzoic acid (0.20 mol) and 100mL of dichloroethane into a reaction bottle, heating to 70-80 ℃, continuing to stir for 0.5h, dropwise adding 28.9g of thionyl chloride (0.24 mol), carrying out heat preservation reaction, removing residual thionyl chloride after the raw materials are completely converted (about 4-5 h), and carrying out decompression desolventizing to obtain 30.6g of o-methylthiobenzoyl chloride with the yield of 82%; the hydrogen chloride gas generated in the reaction process is absorbed into hydrochloric acid with the concentration of 30 percent by water, and the generated sulfur dioxide gas is absorbed into sodium sulfite solution with the concentration of 14.6 percent by 10 percent of sodium hydroxide alkali liquor.
Comparative example 2
The preparation process of N-N-butyl-o-methylthiobenzamide comprises the following steps:
adding o-methylthiobenzoyl chloride (35.5g, 0.19mol) and 100mL of dichloroethane into a reaction bottle, adding triethylamine (21.3g, 0.21mol) at room temperature, stirring for 0.5h, cooling to 0-5 ℃, slowly adding N-butylamine (15.4g, 0.21mol) dropwise, after dropwise addition is finished, carrying out heat preservation reaction until all raw materials are converted (about 2-3 h), washing with water, extracting an aqueous phase with dichloroethane, combining organic phases, drying the organic phases with anhydrous magnesium sulfate, filtering, and carrying out vacuum desolventization to obtain 36.9g of N-N-butyl-o-methylthiobenzamide, wherein the yield is 87%.
Comparative example 3
The preparation process of the 2-n-butyl-1, 2-benzisothiazolin-3-one comprises the following steps:
adding N-N-butyl-o-methylthiobenzamide (39.0g, 0.18mol) and 150mL of tetrachloroethane into a reaction bottle, slowly heating to 35-45 ℃, slowly introducing chlorine (14.2g, 0.2mol), heating to 70 ℃, preserving heat for reaction, cooling after raw materials are completely converted (about 4-5 h), adjusting the pH value to 2-3 by using a 5% sodium carbonate aqueous solution, standing for layering, extracting a water phase by using tetrachloroethane, washing an oil phase by using water, combining organic phases, drying the organic phases by using anhydrous magnesium sulfate, concentrating under reduced pressure, rectifying under reduced pressure to obtain 28.4g of 2-N-butyl-1, 2-benzisothiazolin-3-one, wherein the yield is 79%, and the liquid phase normalized purity is 98.2%; the hydrogen chloride gas generated in the reaction process is absorbed into hydrochloric acid with the concentration of 30% by water, and the generated methyl chloride gas is subjected to cryogenic cooling by liquid nitrogen.
Therefore, the traditional production process using thionyl chloride and chlorine has the defects of extremely toxic raw materials, severe and complicated reaction conditions, large amount of hydrogen chloride and sulfur dioxide waste gas generated in the reaction process, tail gas treatment, large amount of waste water and the like.
Example 1
The o-methylthiobenzoyl chloride is prepared as follows:
adding 33.6g of o-methylthiobenzoic acid (methyl o-toluic acid, 0.20mol), 100mL of dichloroethane and a catalytic amount of N, N-dimethylformamide into a reaction bottle, heating to 50-60 ℃, continuing to stir for 0.5h, then dropwise adding a solution prepared from 20.8g of bis (trichloromethyl) carbonate and 90mL of dichloroethane, carrying out heat preservation reaction, cooling after the raw materials are completely converted (about 2-3 h), concentrating under reduced pressure, crystallizing, and drying under vacuum to obtain 35.5g of o-methylthiobenzoyl chloride with the yield of 95%.
Example 2
The o-methylthiobenzoyl chloride is prepared as follows:
adding o-methylthiobenzoic acid (33.6g, 0.20mol), dichloroethane (100 mL) and a catalytic amount of N, N-dimethylformamide into a reaction bottle, heating to 30-40 ℃, continuing to stir for 0.5h, then dropwise adding a solution prepared from trichloromethyl chloroformate (21.8g, 0.11mol) and 90mL dichloroethane, carrying out heat preservation reaction, cooling after the raw materials are completely converted (about 2-3 h), concentrating under reduced pressure, crystallizing, and drying under vacuum to obtain o-methylthiobenzoyl chloride (34.8 g), wherein the yield is 93%.
Example 3
The preparation process of N-methyl-o-methylthiobenzamide is as follows:
adding o-methylthiobenzoyl chloride (35.5g, 0.19mol) and tetrahydrofuran (100 mL) into a reaction bottle, stirring at room temperature for 0.5h, cooling to-5-0 ℃, slowly dropwise adding a 40% monomethylamine aqueous solution (32.6g, 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 1-2 h), filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 31.3g of N-methyl-o-methylthiobenzamide, wherein the yield is 91%.
Example 4
The preparation process of 2-methyl-1, 2-benzisothiazolin-3-one is as follows:
adding N-methyl-o-methylthiobenzamide (31.3g, 0.17mol), N-bromosuccinimide (33.8g, 0.19mol) and 150mL of tetrachloroethane into a reaction bottle in sequence, slowly heating to 50-60 ℃, preserving heat for reaction, cooling after raw materials are completely converted (about 7-8 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phase with anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and distilling under reduced pressure to obtain 24.6g of 2-methyl-1, 2-benzisothiazolin-3-one, wherein the yield is 86% and the liquid phase normalized purity is more than 99.0%.
Example 5
The preparation process of o-methylthiobenzamide is as follows:
adding 35.5g of o-methylthio benzoyl chloride (0.19 mol) and 100mL of tetrahydrofuran into a reaction bottle, stirring for 0.5h at room temperature, cooling to-15-10 ℃, slowly introducing ammonia gas (7.2g, 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 3-4 h), filtering, washing filter cakes with water, pulping, and drying in vacuum to obtain 29.6g of o-methylthio benzamide, wherein the yield is 93%.
Example 6
The preparation process of the 1, 2-benzisothiazolin-3-ketone comprises the following steps:
adding 28.9g of o-methylthiobenzamide (0.17 mol), 42.9g of N-bromophthalimide (0.19 mol) and 150mL of tetrachloroethane into a reaction bottle in sequence, slowly heating to 50-60 ℃, preserving heat for reaction, cooling after raw materials are completely converted (about 5-6 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phase with anhydrous magnesium sulfate, concentrating under reduced pressure, crystallizing, and drying in vacuum to obtain 22.2g of 1, 2-benzisothiazolin-3-one, wherein the yield is 85%, the liquid phase normalized purity is more than 99.5%, and the HPLC detection purity is 99.9%.
Example 7
The preparation process of N-N-butyl-o-methylthiobenzamide comprises the following steps:
adding 35.5g of o-methylthiobenzoyl chloride (0.19 mol) and 100mL of tetrahydrofuran into a reaction bottle, stirring for 0.5h at room temperature, cooling to 0-5 ℃, slowly dropwise adding N-butylamine (30.7g and 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 2-3 h) after dropwise adding is finished, filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 39.0g of N-N-butyl-o-methylthiobenzamide, wherein the yield is 92%.
Example 8
The preparation process of the 2-n-butyl-1, 2-benzisothiazolin-3-one comprises the following steps:
sequentially adding N-N-butyl-o-methylthiobenzamide (39.0g, 0.18mol), trichloroisocyanuric acid (16.3g, 0.07mol) and 150mL of tetrachloroethane into a reaction bottle, slowly heating to 50-60 ℃, carrying out heat preservation reaction, cooling after raw materials are completely converted (about 6-7 h), filtering, washing filtrate, extracting an aqueous phase by tetrachloroethane, combining organic phases, drying the organic phase by anhydrous magnesium sulfate, concentrating under reduced pressure, and rectifying under reduced pressure to obtain 29.5g of 2-N-butyl-1, 2-benzisothiazolin-3-one, wherein the yield is 82%, the liquid phase normalized purity is more than 99.0%, and the HPLC detection purity is 99.3%.
Example 9
The preparation process of N-cyclohexyl-o-methylthiobenzamide is as follows:
adding 35.5g of o-methylthiobenzoyl chloride (0.19 mol) and 100mL of tetrahydrofuran into a reaction bottle, stirring at room temperature for 0.5h, cooling to 0-5 ℃, slowly dropwise adding cyclohexylamine (41.7g, 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 2-3 h), filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 42.7g of N-cyclohexyl-o-methylthiobenzamide with the yield of 90%.
Example 10
The preparation process of 2-cyclohexyl-1, 2-benzisothiazolin-3-one is as follows:
adding N-cyclohexyl-o-methylthiobenzamide (42.7g, 0.17mol), N-bromophthalimide (42.9g, 0.19mol) and 150mL of tetrachloroethane into a reaction bottle in sequence, slowly heating to 50-60 ℃, carrying out heat preservation reaction, cooling after raw materials are completely converted (about 5-6 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phase with anhydrous magnesium sulfate, concentrating under reduced pressure, crystallizing, and drying in vacuum to obtain 34.1g of 2-cyclohexyl-1, 2-benzisothiazolin-3-one, wherein the yield is 86%, and the normalized purity of the liquid phase is more than 99%.
Example 11
The preparation process of N-tert-butyl-o-methylthiobenzamide is as follows:
adding o-methylthiobenzoyl chloride (35.5g, 0.19mol) and tetrahydrofuran (100 mL) into a reaction bottle, stirring for 0.5h at room temperature, cooling to 0-5 ℃, slowly dropwise adding tert-butylamine (30.7g, 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 2-3 h), filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 38.6g of N-tert-butyl-o-methylthiobenzamide, wherein the yield is 91%.
Example 12
The preparation process of 2-tert-butyl-1, 2-benzisothiazolin-3-one is as follows:
sequentially adding N-tert-butyl-o-methylthiobenzamide (38.0g, 0.17mol), N-bromosuccinimide (33.8g, 0.19mol) and 150mL of tetrachloroethane into a reaction bottle, slowly heating to 50-60 ℃, preserving heat for reaction, cooling after raw materials are completely converted (about 5-6 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phase with anhydrous magnesium sulfate, concentrating under reduced pressure, crystallizing, and drying in vacuum to obtain 30.1g of 2-tert-butyl-1, 2-benzisothiazolin-3-one with the yield of 88% and the liquid phase normalized purity of more than 99%.
Example 13
The preparation process of N- (4-methoxy) benzyl-o-methylthio benzamide is as follows:
adding o-methylthiobenzoyl chloride (35.5g, 0.19mol) and tetrahydrofuran (100 mL) into a reaction bottle, stirring at room temperature for 0.5h, cooling to 0-5 ℃, slowly dropwise adding 4-methoxybenzylamine (57.5g, 0.42mol), keeping the temperature for reaction until the raw materials are completely converted (about 2-3 h), filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 51.9g of N- (4-methoxy) benzyl-o-methylthiobenzamide with the yield of 95%.
Example 14
The preparation process of 2- (4-methoxy) benzyl-1, 2-benzisothiazolin-3-one is as follows:
adding N- (4-methoxy) benzyl-o-methylthiobenzamide (51.9g, 0.18mol), trichloroisocyanuric acid (16.3g, 0.07mol) and tetrachloroethane 150mL into a reaction bottle in sequence, slowly heating to 50-60 ℃, carrying out heat preservation reaction, cooling after raw materials are completely converted (about 5-6 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phases with anhydrous magnesium sulfate, concentrating under reduced pressure, crystallizing, and drying in vacuum to obtain 43.9g of 2- (4-methoxy) benzyl-1, 2-benzisothiazolin-3-one, wherein the yield is 90%, and the normalized purity of the liquid phase is more than 99%.
Example 15
The o-dithiodibenzoyl chloride was prepared as follows:
adding 61.3g of o-dithiodibenzoic acid (0.20 mol), 150mL of dichloroethane and catalytic amount of N, N-dimethylformamide into a reaction bottle, heating to 30-40 ℃, continuing to stir for 0.5h, then dropwise adding a solution prepared from 43.5g of trichloromethyl chloroformate and 130mL of dichloroethane, carrying out heat preservation reaction, cooling after the raw materials are completely converted (about 2-3 h), concentrating under reduced pressure, crystallizing, and drying in vacuum to obtain 61.1g of o-dithiodibenzoyl chloride with the yield of 89%.
Example 16
The disulfide-2, 2' -bis (N-phenylbenzamide) was prepared as follows:
adding 200mL of o-dithiodibenzoyl chloride (61.1g, 0.18mol) and tetrahydrofuran into a reaction bottle, stirring at room temperature for 0.5h, cooling to-5-0 ℃, slowly dropwise adding aniline (72.6g, 0.78mol), keeping the temperature for reaction until the raw materials are completely converted (about 3-4 h), filtering, washing a filter cake with water, pulping, and drying in vacuum to obtain 68.2g of disulfide-2, 2' -bis (N-phenylbenzamide) with the yield of 84%.
Example 17
The preparation process of 2-phenyl-1, 2-benzisothiazolin-3-one is as follows:
adding dithio-2, 2' -bis (N-phenylbenzamide) (68.2g, 0.15mol), 1, 3-dichloro-5, 5-dimethylhydantoin (33.5g, 0.17mol) and 300mL of tetrachloroethane into a reaction bottle in sequence, slowly heating to 40-50 ℃, carrying out heat preservation reaction, cooling after raw materials are completely converted (about 6-7 h), washing with water, extracting an aqueous phase with tetrachloroethane, combining organic phases, drying the organic phase with anhydrous magnesium sulfate, concentrating under reduced pressure, and crystallizing to obtain 58.0g of 2-phenyl-1, 2-benzisothiazolin-3-one, wherein the yield is 85% and the normalized purity of the liquid phase is more than 98.5%.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Claims (8)
1. A synthetic method for preparing 1, 2-benzisothiazolin-3-one compounds of the following formula (1),
wherein R is2Represents hydrogen, alkyl, aryl; the alkyl group comprises straight chain alkyl and substituted alkyl with the carbon number of 1-8, branched chain alkyl and substituted alkyl, and cycloalkyl with the carbon number of 3-6 and substituted cycloalkyl, and the substituent on the alkyl group comprises chlorine, bromine, methyl, ethyl, methoxy and ethoxy; the aryl group comprises phenyl, substituted phenyl, benzyl and substituted benzyl, and the substituent group on the aryl group comprises chlorine, bromine, hydroxyl, methyl, ethyl, isopropyl, tert-butyl, methoxyl and ethoxyl;
the synthesis method comprises the following reaction:
(1) acyl chlorination reaction: reacting o-methylthiobenzoic acid or o-dithiodibenzoic acid serving as a raw material with trichloromethyl chloroformate or bis (trichloromethyl) carbonate to generate o-methylthiobenzoyl chloride or o-dithiodibenzoyl chloride; in the step, the molar ratio of the o-methylthiobenzoic acid to the trichloromethyl chloroformate is 1: 0.5 to 2.5; the molar ratio of the o-dithiodibenzoic acid to the trichloromethyl chloroformate is 1: 1.0 to 5.0; the molar ratio of o-methylthiobenzoic acid to bis (trichloromethyl) carbonate is 1: 0.33 to 1.7; the molar ratio of ortho-dithiodibenzoic acid to bis (trichloromethyl) carbonate is 1: 0.66 to 3.4; the solvent used in the reaction is one or more of dichloromethane, dichloroethane, trichloromethane, tetrachloroethane, N-dimethylformamide, N-dimethylacetamide, toluene, xylene, chlorobenzene and dichlorobenzene solvents; the reaction temperature is-5 to 130 ℃;
(2) amidation: amidating o-methylthio benzoyl chloride or o-dithio dibenzoyl chloride with primary amine containing different substituents to obtain o-methylthio benzamide or o-dithio dibenzoyl amide containing different substituents; in this step, the molar ratio of o-methylthiobenzoyl chloride to primary amine is 1: 1.0 to 3.5; the molar ratio of the o-dithiodibenzoyl chloride to the primary amine is 1: 2.0 to 7.0; the solvent used in the reaction is one or more of dichloromethane, dichloroethane, tetrachloroethane, tetrahydrofuran, methyltetrahydrofuran and dioxane solvent, and the reaction temperature is-20 to 60 ℃;
(3) cyclization reaction; n-alkyl-o-methylthiobenzamide or N-alkyl-o-dithio-benzamide containing different substituents is subjected to cyclization reaction under the action of halide positive ions to synthesize 2-alkyl-1, 2-benzisothiazolin-3-one compounds; in this step, the molar ratio of N-alkyl-o-methylthiobenzamide containing different substituents to the halide cation is 1: 0.6 to 2.8; the molar ratio of N-alkyl-o-dithio-dibenzoyl amide containing different substituents to halide positive ions is 1: 1.2 to 5.6; the solvent used in the reaction is one or more of dichloromethane, dichloroethane, tetrachloroethylene and tetrachloroethane; the halide positive ions are one or more of chloride positive ions, bromide positive ions and iodide positive ions, the reagent for providing the halide positive ions is one or more of N-chlorosuccinimide, N-chlorophthalimide, N-bromosuccinimide, N-bromophthalimide, N-iodosuccinimide, N-iodophthalimide, 1, 3-dichloro-5, 5-dimethylhydantoin, 1, 3-dibromo-5, 5-dimethylhydantoin, 1, 3-diiodo-5, 5-dimethylhydantoin, trichloroisocyanuric acid and chlorobromoisocyanuric acid, and the reaction temperature is-10-140 ℃.
2. The synthesis method according to claim 1, wherein the molar ratio of the o-methylthiobenzoic acid to the trichloromethyl chloroformate in the step (1) is 1: 0.5 to 1.0; the molar ratio of the o-dithiodibenzoic acid to the trichloromethyl chloroformate is 1: 1.0 to 2.0.
3. The synthesis method according to claim 1, wherein the molar ratio of the o-methylthiobenzoic acid to the bis (trichloromethyl) carbonate in the step (1) is 1: 0.35 to 0.7; the molar ratio of ortho-dithiodibenzoic acid to bis (trichloromethyl) carbonate is 1: 0.7 to 1.4.
4. The synthesis method according to claim 1, wherein the reaction temperature in the step (1) is 30-80 ℃.
5. The synthesis method according to claim 1, wherein the molar ratio of o-methylthiobenzoyl chloride to primary amine in the step (2) is 1: 1.1-2.5; the molar ratio of the o-dithiodibenzoyl chloride to the primary amine is 1: 2.2 to 4.5.
6. The synthesis method according to claim 1, wherein the reaction temperature in the step (2) is-10 to 30 ℃.
7. The synthesis method according to claim 1, wherein the molar ratio of the N-alkyl-o-methylthiobenzamide containing different substituents in the step (3) to the halide positive ion is 1: 0.9 to 1.6; the molar ratio of N-alkyl-o-dithio-dibenzoyl amide containing different substituents to halide positive ions is 1: 1.8 to 3.2.
8. The synthesis method according to claim 1, wherein the reaction temperature in the step (3) is 35-70 ℃.
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