CN116283820A - Preparation method of 3-halogeno-1, 2-benzisothiazole - Google Patents
Preparation method of 3-halogeno-1, 2-benzisothiazole Download PDFInfo
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- CN116283820A CN116283820A CN202310289089.7A CN202310289089A CN116283820A CN 116283820 A CN116283820 A CN 116283820A CN 202310289089 A CN202310289089 A CN 202310289089A CN 116283820 A CN116283820 A CN 116283820A
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- benzisothiazole
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000003880 polar aprotic solvent Substances 0.000 claims abstract description 98
- 239000000203 mixture Substances 0.000 claims abstract description 86
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 claims abstract description 70
- 238000005406 washing Methods 0.000 claims abstract description 65
- 238000006243 chemical reaction Methods 0.000 claims abstract description 59
- 239000012454 non-polar solvent Substances 0.000 claims abstract description 44
- -1 thionyl halide Chemical class 0.000 claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- 238000001816 cooling Methods 0.000 claims abstract description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 189
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 15
- 229940117389 dichlorobenzene Drugs 0.000 claims description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 6
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 3
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 claims description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 claims description 3
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 claims description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
- 229940078552 o-xylene Drugs 0.000 claims description 3
- 230000001351 cycling effect Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 89
- BCPVKLRBQLRWDQ-UHFFFAOYSA-N 3-chloro-1,2-benzothiazole Chemical compound C1=CC=C2C(Cl)=NSC2=C1 BCPVKLRBQLRWDQ-UHFFFAOYSA-N 0.000 abstract description 81
- 238000004821 distillation Methods 0.000 abstract description 54
- 239000002994 raw material Substances 0.000 abstract description 17
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 238000005260 corrosion Methods 0.000 abstract description 2
- 230000007797 corrosion Effects 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 112
- 239000000047 product Substances 0.000 description 55
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 36
- 238000004458 analytical method Methods 0.000 description 23
- 238000004811 liquid chromatography Methods 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
- 235000010269 sulphur dioxide Nutrition 0.000 description 18
- 230000000052 comparative effect Effects 0.000 description 14
- 239000007788 liquid Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002351 wastewater Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 5
- 239000002699 waste material Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 230000032798 delamination Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000004291 sulphur dioxide Substances 0.000 description 1
- 238000004065 wastewater treatment Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
The invention relates to the technical field of fine chemical engineering, in particular to a preparation method of 3-halogenated-1, 2-benzisothiazole, which aims to solve the problems of corrosion reaction equipment, bad production conditions and the like existing in the prior art that 3-chloro-1, 2-benzisothiazole is directly purified by a concentration distillation mode. For this purpose, the preparation method of the invention comprises: s1: reacting 1, 2-benzisothiazol-3-one, thionyl halide, polar aprotic solvent, and nonpolar solvent under preset conditions to obtain a mixture containing 3-halo-1, 2-benzisothiazole; s2: cooling a mixture containing 3-halogeno-1, 2-benzisothiazole to a temperature of between 10 ℃ below zero and 40 ℃ and standing for layering to obtain a non-oil phase and an oil phase; s3: and (3) washing and distilling the oil phase in the S2 to obtain the 3-halogeno-1, 2-benzisothiazole and a nonpolar solvent. According to the invention, the proportion of raw materials is controlled, the temperature is reduced and layering is carried out after the reaction, and the oil phase is used for purifying the target product in a mode of washing with water and then distilling, so that the production condition can be effectively improved.
Description
Technical Field
The invention relates to the technical field of fine chemical engineering, and particularly provides a preparation method of 3-halogenated-1, 2-benzisothiazole.
Background
Currently, 3-chloro-1, 2-benzisothiazole can be obtained by reacting 1, 2-benzisothiazol-3-ones, dimethylformamide, and thionyl chloride in a solvent. However, the activity of the reaction is not high, and more dimethylformamide is required in the reaction process. And, the mixture obtained by the above reaction generally includes dimethylformamide, a solvent, remaining thionyl chloride, and by-products of the reaction (e.g., hydrogen chloride, sulfur dioxide, etc.). For this mixture, it is now common to purify the 3-chloro-1, 2-benzisothiazole in the mixture directly by means of concentrated distillation. However, since the mixture contains a large amount of dimethylformamide and strongly acidic substances such as hydrogen chloride and sulfur dioxide generated by side reactions, the reaction equipment is corroded during the concentration and distillation, and the production conditions are relatively bad.
Accordingly, there is a need in the art for a new solution to the above-mentioned problems.
Disclosure of Invention
The invention aims to solve the technical problems, namely the problems of corrosion reaction equipment, bad production conditions and the like existing in the prior art that 3-chloro-1, 2-benzisothiazole is directly purified by a concentration distillation mode.
The invention provides a preparation method of 3-halogenated-1, 2-benzisothiazole, which is characterized by comprising the following steps:
s1: reacting 1, 2-benzisothiazole-3-ketone, thionyl halide, polar aprotic solvent and nonpolar solvent under preset conditions to obtain a mixture containing 3-halogeno-1, 2-benzisothiazole, wherein the molar ratio of 1, 2-benzisothiazole-3-ketone to thionyl halide is a first molar ratio, the first molar ratio is in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazole-3-ketone to polar aprotic solvent to nonpolar solvent is 1 (1.2-4): (1.5-8);
s2: cooling a mixture containing 3-halogeno-1, 2-benzisothiazole to a temperature of between 10 ℃ below zero and 40 ℃ and standing for layering to obtain a non-oil phase and an oil phase;
s3: and (3) washing and distilling the oil phase in the step (S2) to obtain the 3-halogenated-1, 2-benzisothiazole and a nonpolar solvent.
Under the condition of adopting the technical scheme, the mixture containing 3-halogeno-1, 2-benzisothiazole is cooled and kept stand after being reacted to obtain the mixture containing the 3-halogeno-1, 2-benzisothiazole by controlling the proportion of each raw material, and then the oil phase is washed with water and distilled to obtain the final product 3-halogeno-1, 2-benzisothiazole. Because the byproducts of hydrogen chloride and sulfur dioxide generally enter the non-oil phase, the hydrogen chloride and sulfur dioxide in the oil phase are very little, and only a small amount of water is needed to wash the hydrogen chloride and sulfur dioxide in the oil phase basically when the oil phase is washed, equipment cannot be corroded when the oil phase is distilled, and no irritant gas is generated, so that the production condition is improved. Meanwhile, as only the oil phase is required to be washed, the amount of waste water generated in the washing process is small, the waste water treatment pressure is not large, and the required treatment cost is low.
In a preferred technical scheme of the preparation method, the preparation method further comprises the following steps:
s4: adding a preset amount of polar aprotic solvent to the non-oil phase in the step S2 to obtain a mixture containing the polar aprotic solvent;
s5: replacing the polar aprotic solvent in S1 with the mixture containing the polar aprotic solvent in S4, and enabling the mixture to react with 1, 2-benzisothiazol-3-one, thionyl halide and nonpolar solvent under the preset conditions in S1 to obtain a new mixture containing 3-halogeno-1, 2-benzisothiazol, wherein the molar ratio of 1, 2-benzisothiazol-3-one to thionyl halide is a second molar ratio, and the second molar ratio is in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazol-3-one to nonpolar solvent is 1 (1.5-8);
s6: and cycling from S2 to S5.
Under the condition of adopting the technical scheme, a mode of adding a small amount of polar aprotic solvent into the non-oil phase is adopted to replace a large amount of polar aprotic solvent which is required to be added in the original reaction process, and residual 1, 2-benzisothiazole-3-ketone, thionyl halide and polar aprotic solvent, especially polar aprotic solvent in the non-oil phase are fully utilized, so that the dosage of the polar aprotic solvent can be effectively reduced, the waste of effective raw materials can be effectively avoided, and the production cost can be greatly reduced.
In the preferred technical scheme of the preparation method, the preset amount of the polar aprotic solvent added in the S4 is 5% -10% of the amount of the polar aprotic solvent in the S1.
Under the condition of adopting the technical scheme, a large amount of polar aprotic solvent which is originally required can be replaced by adding a small amount of polar aprotic solvent, and the polar aprotic solvent fully reacts with 1, 2-benzisothiazole-3-ketone, thionyl halide and nonpolar solvent to obtain the target product 3-halogenated-1, 2-benzisothiazole, so that the use amount of the polar aprotic solvent can be greatly reduced, the utilization efficiency of the polar aprotic solvent is improved, and the production cost of enterprises is reduced.
In a preferred embodiment of the above preparation method, the first molar ratio is greater than the second molar ratio; and/or
And in the step S6, the number of the loops from the step S2 to the step S5 is more than or equal to 5.
Thus, the polar aprotic solvent in the non-oil phase can be fully utilized by circulating the S2 to S5 for several times, the utilization efficiency of the polar aprotic solvent can be better improved, and the waste of effective raw materials can be avoided.
In a preferred technical scheme of the preparation method, the reaction temperature in the preset condition in the step S1 is 65-120 ℃ and the reaction time is 2-6 hours.
In a preferred technical scheme of the preparation method, the reaction temperature in the S1 is 75-100 ℃ and the reaction time is 3-4 hours.
By reacting 1, 2-benzisothiazol-3-one, thionyl halide, polar aprotic solvent, and nonpolar solvent at 75-100 ℃ for 3-4 hours, higher reaction efficiency and thus higher yield of 3-halo-1, 2-benzisothiazole can be obtained.
In a preferred technical scheme of the preparation method, the nonpolar solvent is at least one of toluene, chlorobenzene, o-dichlorobenzene, benzene, m-dichlorobenzene, o-xylene, m-xylene, p-xylene, dichloroethane, chlorobutane, bromobutane and pentane.
In a preferred embodiment of the above preparation method, the nonpolar solvent is chlorobenzene, dichlorobenzene or toluene.
In a preferred embodiment of the above preparation method, the polar aprotic solvent is at least one of dimethylformamide, dimethylacetamide, 1, 3-dimethyl-2-imidazolidinone and hexamethylphosphoric triamide.
In a preferred embodiment of the above preparation method, the polar aprotic solvent is dimethylformamide.
Drawings
Preferred embodiments of the present invention are described below with reference to the accompanying drawings, in which:
FIG. 1 is a flow chart of a method of preparing 3-halo-1, 2-benzisothiazoles in accordance with one embodiment of the present invention;
FIG. 2 is a liquid chromatograph of the target product obtained by the first reaction in embodiment 1 of the present invention;
FIG. 3 is a liquid chromatograph of the target product obtained by the second reaction in embodiment 1 of the present invention;
FIG. 4 is a liquid chromatograph of the target product obtained by the reaction in comparative example 1 of the present invention.
Detailed Description
Preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are merely for explaining the technical principles of the present invention, and are not intended to limit the scope of the present invention.
At present, a large amount of wastewater is generated in the process of preparing 3-chloro-1, 2-benzisothiazole by using 1, 2-benzisothiazole-3-ketone, dimethylformamide and thionyl chloride, and the subsequent treatment cost is high. Therefore, the 3-halogeno-1, 2-benzisothiazole can be obtained by standing and layering a mixture generated after the reaction of the 1, 2-benzisothiazole-3-ketone, thionyl halide, a polar aprotic solvent and a nonpolar solvent, and only water washing and distillation are needed for an oil phase, so that the amount of generated wastewater is greatly reduced, the subsequent treatment cost is reduced, and the use amount of the polar aprotic solvent is reduced.
In the invention, 1, 2-benzisothiazole-3-ketone, thionyl halide, polar aprotic solvent and nonpolar solvent are taken as raw materials to prepare 3-halogeno-1, 2-benzisothiazole. The following steps for preparing 3-halo-1, 2-benzisothiazoles are illustrated in connection with FIG. 1:
s1: reacting 1, 2-benzisothiazole-3-ketone, thionyl halide, polar aprotic solvent and nonpolar solvent under preset conditions to obtain a mixture containing 3-halogeno-1, 2-benzisothiazole, wherein the molar ratio of 1, 2-benzisothiazole-3-ketone to thionyl halide is a first molar ratio, the first molar ratio is in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazole-3-ketone to polar aprotic solvent to nonpolar solvent is 1 (1.2-4) (1.5-8).
In this example, the chemical formula (1) of 1, 2-benzisothiazol-3-one is:
wherein R is 1 Represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, an alkoxycarbonyl group having 2 to 5 carbon atoms, a nitro group or a halogen atom.
The chemical formula (2) of the 3-halogeno-1, 2-benzisothiazole is:
wherein R is 1 R in the formula (1) 1 And X represents a halogen atom.
In one possible embodiment, the preset conditions in S1 generally include a reaction temperature and a reaction time, wherein the reaction temperature ranges from 65 to 120 ℃ and the reaction time ranges from 2 to 6 hours.
Preferably, the reaction temperature is 75-100 ℃, and the raw materials can fully participate in the reaction within the temperature range, so that the reaction activity is better, the reaction efficiency is higher, and the yield of the target product 3-halogenated-1, 2-benzisothiazole is higher.
Preferably, the reaction time is in the range of 3 to 4 hours, and the raw materials can sufficiently participate in the reaction within the reaction time, and more 3-halogeno-1, 2-benzisothiazole can be produced, thereby obtaining a higher yield.
S2: cooling the mixture containing 3-halogeno-1, 2-benzisothiazole to-10-40 ℃ and standing for layering to obtain a non-oil phase and an oil phase.
S3: and (3) washing and distilling the oil phase in the S2 to obtain the 3-halogeno-1, 2-benzisothiazole and the nonpolar solvent.
In the prior art, after the reaction of 1, 2-benzisothiazol-3-one, thionyl halide, polar aprotic solvent and nonpolar solvent to give a mixture containing 3-halo-1, 2-benzisothiazole, the mixture is usually directly subjected to concentration distillation to purify 3-halo-1, 2-benzisothiazole. However, since the mixture contains a large amount of polar aprotic solvents, by-products of hydrogen chloride and sulfur dioxide, which are strong acidic substances, the reaction equipment is corroded during the concentration and distillation process, and the production conditions are relatively bad. For this purpose, the invention controls the proportion of each raw material and the reaction condition (specific proportion is stated below), so that the mixture containing 3-halogeno-1, 2-benzisothiazole generated by the reaction in S1 can automatically delaminate after being cooled to-10-40 ℃ and form an oil phase positioned at the upper layer and a non-oil phase positioned at the lower layer, and then the oil phase and the non-oil phase are separated by a liquid separation mode (such as liquid separation by using a separating funnel, etc.), wherein the oil phase mainly comprises 3-halogeno-1, 2-benzisothiazole and a non-polar solvent, and the non-oil phase mainly comprises unreacted polar aprotic solvent and thionyl halide, and hydrogen chloride and sulfur dioxide generated by side reaction in the reaction process, etc.
The oil phase may also have a small amount of polar aprotic solvent. Meanwhile, part of hydrogen chloride and sulfur dioxide enter the oil phase, and although the amount of hydrogen chloride and sulfur dioxide is small, the equipment and the production conditions are affected. Therefore, the oil phase is washed with a small amount of water before the oil phase is distilled, and after each washing, the oil phase is stood and layered to obtain a new oil phase and a new water phase. After water washing, most of polar aprotic solvents, hydrogen chloride and sulfur dioxide can be washed into water, so that hydrogen chloride and sulfur dioxide do not corrode reaction equipment during subsequent distillation of the oil phase, and the production condition is improved. The water phase obtained in the water washing process mainly comprises hydrogen chloride and sulfur dioxide, and is used as wastewater generated in the production process for treatment.
Preferably, after the oil phase obtained in the step S2 is washed three times, the obtained new oil phase basically only comprises 3-halogeno-1, 2-benzisothiazole and a nonpolar solvent, is slightly acidic, is favorable for subsequent distillation treatment, does not substantially corrode reaction equipment in the distillation treatment process, and well improves the production conditions. Meanwhile, less wastewater is generated by three times of water washing.
In one possible embodiment, distillation is carried out by distillation under reduced pressure when the oil phase is distilled. Specifically, in the reduced pressure distillation process, the vacuum degree is-0.09 MPa to 0.095MPa, the boiling point of the nonpolar solvent is different from that of the 3-halogenated-1, 2-benzisothiazole, and the nonpolar solvent belongs to fractions with different temperature sections respectively. Taking non-polar solvent as chlorobenzene, 3-halogeno-1, 2-benzisothiazole as 3-chloro-1, 2-benzisothiazole as example, distillation is carried out under the condition of vacuum degree of-0.095 MPa, the fraction between 80 ℃ and 132 ℃ is chlorobenzene, and the fraction between 135 ℃ and 165 ℃ is 3-chloro-1, 2-benzisothiazole. Chlorobenzene obtained in the reduced pressure distillation process can be used as the nonpolar solvent in S1.
S4: adding a predetermined amount of a polar aprotic solvent to the non-oil phase in S2 to obtain a mixture comprising the polar aprotic solvent.
The non-oil phase obtained in the step S2 mainly comprises unreacted polar aprotic solvent, thionyl halide, hydrogen chloride and sulfur dioxide generated by side reaction in the reaction process, and a preset amount of polar aprotic solvent is added into the non-oil phase, so that the obtained mixture contains more polar aprotic solvent. It is noted that the preset amount is much smaller than the amount of polar aprotic solvent required in S1.
S5: replacing the polar aprotic solvent in S1 with the mixture containing the polar aprotic solvent in S4, and reacting the 1, 2-benzisothiazol-3-one, the thionyl halide, the mixture containing the polar aprotic solvent and the nonpolar solvent under the preset conditions in S1 to obtain a new mixture containing 3-halogeno-1, 2-benzisothiazol. Wherein the molar ratio of the 1, 2-benzisothiazole-3-ketone to the thionyl halide is a second molar ratio, the second molar ratio ranges from 1:1.6 to 1:1.2, and the molar ratio of the 1, 2-benzisothiazole-3-ketone to the polar aprotic solvent is unchanged.
The preset conditions (reaction temperature and reaction time) in S5 are the same as those in S1, changing only the source of the polar aprotic solvent and the molar ratio of 1, 2-benzisothiazol-3-one to thionyl halide. That is, the non-oil phase in S2 added with a small amount of polar aprotic solvent is used to replace a large amount of polar aprotic solvent originally required, so that the residual 1, 2-benzisothiazolin-3-one, thionyl halide and polar aprotic solvent in the non-oil phase are fully utilized, and particularly the polar aprotic solvent is not needed to be added as in S1, thereby effectively reducing the dosage of the polar aprotic solvent, avoiding the waste of effective raw materials and greatly reducing the production cost. The nonpolar solvent required for the reaction in S5 may be the nonpolar solvent obtained by distillation in S3 in whole or in part, and may be used fully.
S6: and (5) circulating S2 to S5.
After the reaction in S5 to give a new mixture comprising 3-halo-1, 2-benzisothiazole, S2 to S5 are recycled. That is, the new mixture obtained in S5 is cooled to-10 to 40 ℃, and then left to stand for delamination, thus obtaining a new non-oil phase and a new oil phase. The new oil phase is washed with water and distilled to obtain 3-halogeno-1, 2-benzisothiazole and nonpolar solvent. Adding proper polar aprotic solvent into the new non-oil phase, and reacting the formed mixture with 1, 2-benzisothiazole-3-ketone, thionyl halide and nonpolar solvent again to obtain the new mixture containing 3-halogeno-1, 2-benzisothiazole. The method is repeated for a plurality of times, so that the polar aprotic solvent remained in the non-oil phase can be more fully utilized, the dosage of the polar aprotic solvent is reduced, and the production cost is reduced.
Preferably, when the number of cycles of S2 to S5 is greater than or equal to 5, the polar aprotic solvent in the non-oil phase can be more fully utilized, the utilization efficiency of the polar aprotic solvent can be better improved, the waste of effective raw materials can be avoided, and the production cost can be reduced. Obviously, the number of cycles of S2 to S5 described above may also be less than 5.
In one possible embodiment, the preset amount of the polar aprotic solvent added in S4 is 5% to 10% of the amount of the polar aprotic solvent in S1. Therefore, only a small amount of polar aprotic solvent is required to be added, and the reaction can be fully carried out with 1, 2-benzisothiazole-3-ketone, thionyl halide and nonpolar solvent to obtain the target product 3-halogenated-1, 2-benzisothiazole. In addition, under the condition that only a small amount of polar aprotic solvent is newly added, the yield of the 3-halogeno-1, 2-benzisothiazole obtained by the reaction is slightly higher than that when the polar aprotic solvent is directly used as a raw material (specific application is given in specific examples 1-6 below), which also shows that the polar aprotic solvent in the non-oil phase in S2 is fully utilized, so that the use amount of the polar aprotic solvent can be greatly reduced, the use efficiency of the polar aprotic solvent is improved, and the production cost of enterprises is reduced.
The preset amount of the polar aprotic solvent added in S4 may be 3%, 4% or the like of the amount of the polar aprotic solvent, or 13%, 18% or the like of the amount of the polar aprotic solvent.
In one possible embodiment, the molar ratio of 1, 2-benzisothiazol-3-one to polar aprotic solvent to nonpolar solvent in S1 is 1 (1.2-4): 1.5-8. The first molar ratio of 1, 2-benzisothiazol-3-one to thionyl halide in S1 and the second molar ratio in S5 are both in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazol-3-one to nonpolar solvent in S5 is still 1 (1.5-8). Under the raw material proportion, the mixture containing 3-halogeno-1, 2-benzisothiazole obtained by reacting the 1, 2-benzisothiazole-3-ketone, thionyl halide, polar aprotic solvent and nonpolar solvent in S1 and S5 can be layered by standing after being cooled to-10-40 ℃ to form a non-oil phase and an oil phase. This is because the inventors found that when the mixture obtained by the reaction under the above reaction conditions in the above raw material ratio is cooled to-10 to 40 ℃, part of the by-product hydrogen chloride and sulfur dioxide react with a weakly basic polar aprotic solvent (for example, dimethylformamide or the like) to form a strong acid and weak base salt, and an acid-base equilibrium is achieved. This also results in the formation of a new phase, i.e. a non-oil phase, of the polar aprotic solvent, the thionyl halide, and hydrogen chloride and sulphur dioxide, which is no longer miscible with the non-polar solvent and 3-halo-1, 2-benzisothiazole, thus forming two mutually immiscible phases and achieving delamination. That is, the invention controls the proportion of the raw materials, so that the mixture obtained by the reaction in S1 and S5 can be layered up and down after being cooled to-10-40 ℃, and the main target product 3-halogeno-1, 2-benzisothiazole can be separated from unreacted raw materials and reaction byproducts by standing, thus reducing the processing amount of the oil phase which needs washing and distillation in the follow-up process and simplifying the production process.
In S5, the non-oil phase added with the polar aprotic solvent is used for replacing the original polar aprotic solvent in S1, and when the reaction in S1 occurs, the acid-base balance is destroyed because the reaction temperature is far higher than the cooling temperature of minus 10-40 ℃, and the polar aprotic solvent is dissociated from hydrogen chloride and sulfur dioxide and takes part in the reaction as a raw material. New hydrogen chloride and sulfur dioxide are generated in the reaction process, and after the reaction is finished and the temperature is reduced to-10 ℃ to 40 ℃, the hydrogen chloride and the sulfur dioxide react with a weak alkaline polar aprotic solvent (such as dimethylformamide and the like) again to reach acid-base balance, so that two phases are formed.
In one possible embodiment, the first molar ratio is less than or equal to the second molar ratio, that is, when the amount of the starting 1, 2-benzisothiazol-3-one is the same and the amount of the target product obtained is the same, the amount of thionyl halide required in S5 can be smaller than that in S1 (see in particular examples 1 to 6 below), which also means that the non-oil phase in S2 also contains thionyl halide and is recycled in S5, which also achieves recycling of thionyl halide in the non-oil phase, reduces consumption of the starting thionyl halide and improves the utilization of the starting material. Obviously, the first molar ratio may also be greater than the second molar ratio.
In one possible embodiment, the non-polar solvent is at least one of toluene, chlorobenzene, o-dichlorobenzene, benzene, m-dichlorobenzene, o-xylene, m-xylene, p-xylene, dichloroethane, chlorobutane, bromobutane, pentane.
Preferably, the nonpolar solvent is chlorobenzene, dichlorobenzene or toluene.
In one possible embodiment, the polar aprotic solvent is at least one of dimethylformamide, dimethylacetamide, 1, 3-dimethyl-2-imidazolidinone, and hexamethylphosphoric triamide.
Preferably, the polar aprotic solvent is dimethylformamide.
In this embodiment, the halogen atom X in the chemical formula (2) of 3-halo-1, 2-benzisothiazole may be a fluorine atom, a chlorine atom, a bromine atom or the like.
The following will specifically illustrate possible implementation manners of the preparation method of the present invention by taking X in the chemical formula (2) as a chlorine atom and repeating steps S2 to S5 once as an example. Correspondingly, when X is a chlorine atom, the thionyl halide is thionyl chloride.
Example 1
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, the temperature is controlled between 80 ℃ and 85 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, then the mixture is cooled to about 20 ℃, and then the mixture is stood and layered.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 99g of target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.36% through liquid chromatography analysis.
0.109mol of DMF was added to the lower non-oil phase and reacted with 0.66mol of BIT, 2.665mol of chlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 20 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to the above-mentioned upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 103g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was determined to be 98.92% by liquid chromatography analysis.
Comparative example 1
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 90g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 98.42% through liquid chromatography analysis.
Example 2
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 1.36mol of dichlorobenzene and 1.09mol of dimethylformamide (DMF for short) were added, the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, the temperature is controlled between 80 ℃ and 85 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, and then the mixture is cooled to about 20 ℃. Then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of dichlorobenzene and a target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 95g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.4% through liquid chromatography analysis.
To the lower non-oil phase was added 0.109mol of DMF which was reacted with 0.66mol of BIT, 1.36mol of dichlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 20 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to those of the upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 105g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was 99.1% as determined by liquid chromatography analysis.
Comparative example 2
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 1.36mol of dichlorobenzene and 1.09mol of dimethylformamide (DMF for short) were added, the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of dichlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 92g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 98.6% through liquid chromatography analysis.
Example 3
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 3.256mol of toluene and 1.09mol of dimethylformamide (DMF for short) were added, and the mixture was heated to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, the temperature is controlled between 80 ℃ and 85 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, and then the mixture is cooled to about 20 ℃. Then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of dichlorobenzene and a target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 98g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.28% through liquid chromatography analysis.
To the lower non-oil phase was added 0.054mol of DMF which was reacted with 0.66mol of BIT, 3.256mol of toluene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 20 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to those of the upper oil phase, and after 3 times of water washing, reduced pressure distillation was performed to obtain 103g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was 99.1% as determined by liquid chromatography analysis.
Comparative example 3
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 3.256mol of toluene and 1.09mol of dimethylformamide (DMF for short) were added, and the mixture was heated to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of dichlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 91g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 98.6% through liquid chromatography analysis.
Example 4
2.665mol of chlorobenzene and 1.36mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, the temperature is controlled between 80 ℃ and 85 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, and then the mixture is cooled to about 25 ℃. Then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 100g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.38% through liquid chromatography analysis.
0.136mol of DMF was added to the lower non-oil phase and reacted with 0.66mol of BIT, 2.665mol of chlorobenzene and 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 25 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to the above-mentioned upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 104g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was determined to be 99.06% by liquid chromatography analysis.
Comparative example 4
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 93g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 98.6% through liquid chromatography analysis.
Example 5
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, the temperature is controlled between 80 ℃ and 85 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, and then the mixture is cooled to about 30 ℃. Then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 100g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.45% through liquid chromatography analysis.
To the lower non-oil phase was added 0.054mol of DMF which was reacted with 0.66mol of BIT, 2.665mol of chlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 20 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to the above-mentioned upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 102g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was determined to be 99.12% by liquid chromatography analysis.
Comparative example 5
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 4 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 90g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 98.7% through liquid chromatography analysis.
Example 6
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 0.906mol of dichlorobenzene and 1.09mol of dimethylformamide (DMF for short) were added, the mixture was heated to 80℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dripping thionyl chloride, the temperature is controlled between 80 ℃ and 85 ℃. After the dripping is completed, the temperature is controlled between 85 ℃ and 90 ℃, BIT, chlorobenzene, DMF and thionyl chloride react for 3 hours, and then the mixture is cooled to about 20 ℃. Then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 101g of target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.6% through liquid chromatography analysis.
0.067mol of DMF was added to the lower non-oil phase and reacted with 0.66mol of BIT, 0.906mol of dichlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to about 20 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to those of the upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 105g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was 99.4% as determined by liquid chromatography analysis.
Comparative example 6
To 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), 0.906mol of dichlorobenzene and 1.09mol of dimethylformamide (DMF for short) were added, the mixture was heated to 80℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dripping thionyl chloride, the temperature is controlled between 80 ℃ and 85 ℃. After the dripping is completed, controlling the temperature between 85 and 90 ℃, after BIT, chlorobenzene, DMF and thionyl chloride react for 3 hours, adding 400g of water into the mixture for water washing, standing and layering, and continuously water-washing the obtained oil phase twice, wherein the water consumption is 400g each time. The oil phase after 3 times of water washing is subjected to reduced pressure distillation, the vacuum degree is-0.095 MPa in the reduced pressure distillation process, two fractions of dichlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, 92g of target product 3-chloro-1, 2-benzisothiazole can be obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.1% through liquid chromatography analysis.
Example 7
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, reacting BIT, chlorobenzene, DMF and thionyl chloride for 4 hours, cooling to 40 ℃, and then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 98g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.40% through liquid chromatography analysis.
0.109mol of DMF was added to the lower non-oil phase and reacted with 0.66mol of BIT, 2.665mol of chlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to 40 ℃, then left to stand and delaminated. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to those of the upper oil phase, and after 3 times of water washing, reduced pressure distillation was performed to obtain 102g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was 98.82% as determined by liquid chromatography analysis.
Example 8
2.665mol of chlorobenzene and 1.09mol of Dimethylformamide (DMF) were added to 0.66mol of 1, 2-benzisothiazol-3-one (BIT for short), the mixture was warmed to 75℃and then 0.92mol of thionyl chloride was slowly dropped. In the process of dropwise adding thionyl chloride, the temperature is controlled between 75 ℃ and 80 ℃. After the dripping is completed, controlling the temperature between 80 and 85 ℃, reacting BIT, chlorobenzene, DMF and thionyl chloride for 4 hours, cooling to-10 ℃, and then standing and layering.
Adding 50g of water into the upper oil phase for water washing, standing and layering to obtain an oil phase, and continuing water washing twice, wherein the water consumption is 50g each time. And (3) carrying out reduced pressure distillation on the oil phase subjected to the water washing for 3 times, wherein the vacuum degree is-0.095 MPa in the reduced pressure distillation process, and two fractions of chlorobenzene and target product 3-chloro-1, 2-benzisothiazole are respectively obtained, wherein 100g of the target product 3-chloro-1, 2-benzisothiazole is obtained, and the purity of the 3-chloro-1, 2-benzisothiazole is determined to be 99.28% through liquid chromatography analysis.
0.109mol of DMF was added to the lower non-oil phase and reacted with 0.66mol of BIT, 2.665mol of chlorobenzene, 0.85mol of thionyl chloride in the same manner as described above to give a novel 3-chloro-1, 2-benzisothiazole containing mixture. The new mixture was cooled to-10 ℃ and then allowed to stand and delaminate. The obtained upper oil phase was substantially similar in treatment process and treatment conditions to the above-mentioned upper oil phase, and after 3 times of water washing, reduced pressure distillation was carried out to obtain 101g of the target product 3-chloro-1, 2-benzisothiazole, and the purity of the 3-chloro-1, 2-benzisothiazole was determined to be 98.92% by liquid chromatography analysis.
Based on the above examples 1-8 and comparative examples 1-6, it can be seen that the non-oil phase added with a small amount of polar aprotic solvent (chlorobenzene, dichlorobenzene, toluene) is used to replace the reaction with a reduced dosage of thionyl chloride, which is a reaction with a large amount of polar aprotic solvent originally participating in the reaction, in the examples, that is, the second reaction, and the yield of the obtained 3-chloro-1, 2-benzisothiazole is equivalent to, or even slightly higher than, the yield of the first reaction, which also means that the polar aprotic solvent and thionyl chloride in the non-oil phase are fully utilized in the second reaction. Therefore, the utilization efficiency of raw materials is improved, and the production cost of enterprises is reduced. Furthermore, as can be seen from examples 1 to 8 and comparative examples 1 to 6, the amount of water used in washing the oil phase before distillation was smaller in each example than in each comparative example, that is, the amount of wastewater generated in the process of producing the target product 3-chloro-1, 2-benzisothiation by the method of the present invention was smaller and the amount of wastewater to be treated was smaller.
In this example, the purity of the target product 3-chloro-1, 2-benzisothiazole obtained in examples 1 to 8 and comparative examples 1 to 6 described above was analyzed by means of liquid chromatography.
Wherein, the manufacturer of the liquid chromatograph is Shanghai Wu Feng scientific instrument Co., ltd, and the model is LC100. The column was manufactured by Akzo Nobel, sweden, model Kromasil100A C, 7 μm, size 250mm 4.6mm. The detection wavelength is 254nm, the mobile phase is methanol and water, the molar ratio of methanol to water is 3:1, the flow rate is 0.8ml/min, and the chromatographic column temperature is 25 ℃.
And (3) dissolving 0.1g of the target product 3-chloro-1, 2-benzisothiazole in 4ml of methanol, putting into an ultrasonic instrument, and shaking and mixing for a plurality of minutes (for example, 6 minutes and the like) to prepare the liquid to be detected. 2 μl of the solution to be measured was injected into the liquid chromatograph, the chromatogram was recorded according to the conditions described above, and the content of each component in the chromatogram was calculated by using an area normalization method.
Specifically, in order to clearly illustrate the purity of the target product, liquid chromatograms and analysis results of 3-chloro-1, 2-benzisothiazole obtained in the above example 1 and comparative example 1 are shown in fig. 2 to 4 of the specification, respectively.
As can be seen from the graphs shown in FIGS. 2 to 4, the main components in the liquid to be tested are 3-chloro-1, 2-benzisothiazole. Wherein the content of 3-chloro-1, 2-benzisothiazole in the target product obtained by the first reaction in example 1 was 99.36%, the content of 3-chloro-1, 2-benzisothiazole in the target product obtained by the second reaction was 98.92%, and the content of 3-chloro-1, 2-benzisothiazole in the target product obtained by the reaction in comparative example 1 was 98.42%.
From this, it is apparent that the purity of the target product obtained by the reaction in example 1 of the present invention, which was obtained by first standing and layering after the reaction, washing the oil phase with water and distilling the oil phase was higher, and the purity of the target product obtained by the reaction by using the non-oil phase with a small amount of polar aprotic solvent instead of a large amount of polar aprotic solvent was approximately equal to that obtained in comparative example 1. The non-oil phase added with a small amount of polar aprotic solvent can effectively replace the pure polar aprotic solvent, so that the polar aprotic solvent in the non-oil phase can be fully utilized on the basis of ensuring the purity of a target product, and the popularization and application of the technology are facilitated.
In summary, in the preferred technical scheme of the invention, the mixture obtained by reacting 1, 2-benzisothiazol-3-one, thionyl halide, polar aprotic solvent and nonpolar solvent is cooled to-10-40 ℃, then the mixture is stood for layering, the oil phase is washed with water and distilled to obtain a target product, a small amount of polar aprotic solvent is added into the non-oil phase and then reacts with 1, 2-benzisothiazol-3-one, thionyl halide and nonpolar solvent to obtain a new mixture, the new mixture is cooled and stood for layering to obtain a new oil phase and a non-oil phase, the oil phase and the non-oil phase are treated respectively according to the treatment mode, and the steps are repeated. Therefore, the polar aprotic solvent in the non-oil phase can be recycled, the dosage of the polar aprotic solvent is reduced, and the production cost is further reduced. Meanwhile, the oil phase is distilled after being washed, so that the production condition is effectively improved. In addition, as only the oil phase is required to be washed, less waste water is generated in the washing process, and the subsequent treatment cost is low.
Although the steps are described in the above-described sequential order in the above-described embodiments, it will be appreciated by those skilled in the art that, in order to achieve the effects of the present embodiments, the steps need not be performed in such order, and may be performed simultaneously (in parallel) or in reverse order, and these simple variations are within the scope of the present application.
Thus far, the technical solution of the present invention has been described in connection with the preferred embodiments shown in the drawings, but it is easily understood by those skilled in the art that the scope of protection of the present invention is not limited to these specific embodiments. Equivalent modifications and substitutions for related technical features may be made by those skilled in the art without departing from the principles of the present invention, and such modifications and substitutions will fall within the scope of the present invention.
Claims (10)
1. A method for preparing 3-halo-1, 2-benzisothiazole, which is characterized by comprising the following steps:
s1: reacting 1, 2-benzisothiazole-3-ketone, thionyl halide, polar aprotic solvent and nonpolar solvent under preset conditions to obtain a mixture containing 3-halogeno-1, 2-benzisothiazole, wherein the molar ratio of 1, 2-benzisothiazole-3-ketone to thionyl halide is a first molar ratio, the first molar ratio is in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazole-3-ketone to polar aprotic solvent to nonpolar solvent is 1 (1.2-4): (1.5-8);
S2: cooling a mixture containing 3-halogeno-1, 2-benzisothiazole to a temperature of between 10 ℃ below zero and 40 ℃ and standing for layering to obtain a non-oil phase and an oil phase;
s3: and (3) washing and distilling the oil phase in the step (S2) to obtain the 3-halogenated-1, 2-benzisothiazole and a nonpolar solvent.
2. The method of manufacturing according to claim 1, further comprising the steps of:
s4: adding a preset amount of polar aprotic solvent to the non-oil phase in the step S2 to obtain a mixture containing the polar aprotic solvent;
s5: replacing the polar aprotic solvent in S1 with the mixture containing the polar aprotic solvent in S4, and enabling the mixture to react with 1, 2-benzisothiazol-3-one, thionyl halide and nonpolar solvent under the preset conditions in S1 to obtain a new mixture containing 3-halogeno-1, 2-benzisothiazol, wherein the molar ratio of 1, 2-benzisothiazol-3-one to thionyl halide is a second molar ratio, and the second molar ratio is in the range of 1:1.6-1:1.2, and the molar ratio of 1, 2-benzisothiazol-3-one to nonpolar solvent is 1 (1.5-8);
s6: and cycling from S2 to S5.
3. The preparation method according to claim 2, wherein the preset amount of the polar aprotic solvent added in S4 is 5% to 10% of the amount of the polar aprotic solvent in S1.
4. The method of preparing according to claim 2, wherein the first molar ratio is less than or equal to the second molar ratio; and/or
And in the step S6, the number of the loops from the step S2 to the step S5 is more than or equal to 5.
5. The method according to claim 1, wherein the reaction temperature in the preset condition in S1 is in the range of 65 to 120 ℃ and the reaction time is 2 to 6 hours.
6. The process according to claim 5, wherein the reaction temperature in S1 is 75 to 100℃and the reaction time is 3 to 4 hours.
7. The method according to claim 1, wherein the nonpolar solvent is at least one of toluene, chlorobenzene, o-dichlorobenzene, benzene, m-dichlorobenzene, o-xylene, m-xylene, p-xylene, dichloroethane, chlorobutane, bromobutane, and pentane.
8. The method according to claim 7, wherein the nonpolar solvent is chlorobenzene, dichlorobenzene or toluene.
9. The method according to claim 1, wherein the polar aprotic solvent is at least one of dimethylformamide, dimethylacetamide, 1, 3-dimethyl-2-imidazolidinone, and hexamethylphosphoric triamide.
10. The method of claim 9, wherein the polar aprotic solvent is dimethylformamide.
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