WO2020029720A1 - 一种2-氯-6-甲硫基甲苯的制备方法 - Google Patents

一种2-氯-6-甲硫基甲苯的制备方法 Download PDF

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WO2020029720A1
WO2020029720A1 PCT/CN2019/094294 CN2019094294W WO2020029720A1 WO 2020029720 A1 WO2020029720 A1 WO 2020029720A1 CN 2019094294 W CN2019094294 W CN 2019094294W WO 2020029720 A1 WO2020029720 A1 WO 2020029720A1
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compound
chloro
reaction
methylthiotoluene
preparation
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PCT/CN2019/094294
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French (fr)
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沈运河
熊国银
赵晓俊
范富云
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安徽久易农业股份有限公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
    • C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
    • C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides

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  • the invention relates to the technical field of organic chemical engineering, and in particular to a method for preparing 2-chloro-6-methylthiotoluene.
  • Sulfonone is a new type of triketone herbicide with high activity, low dosage and relatively safe.
  • 2-Chloro-6-methylthiotoluene is a key intermediate for the production of sulfanone.
  • Foreign patent (US6211216B) The synthetic method reported in this article uses 2,6-dichlorotoluene as a raw material and highly polar and highly toxic hexamethylphosphoryl triamine as a solvent. This method is highly harmful to the environment and uses formazan, which is unsafe in industrial production.
  • Solid sodium thiolate Traditional method for the synthesis of hexamethylphosphoryl triamine in 2-chloro-6-methylthiotoluene is difficult to recycle, high cost, and high environmental pollution; it has high cost, is not easy to operate, has large pollution, and has a high safety risk , Not environmental protection and other shortcomings, not suitable for large-scale industrial production.
  • the technical problem to be solved by the present invention is to provide a method for preparing 2-chloro-6-methylthiotoluene.
  • the method has fewer reaction steps, low cost, easy operation and less pollution. Suitable for the preparation of 2-chloro-6-methylthiotoluene required for large-scale industrial production.
  • the invention provides a method for preparing 2-chloro-6-methylthiotoluene, including:
  • the step 1) is specifically: mixing a compound of the formula (I), sodium nitrite and an acid to obtain a compound of the formula (III);
  • the acid is hydrochloric acid or sulfuric acid.
  • the molar ratio of the compound I to the acid is 1: 2 to 1: 5;
  • the molar ratio of the compound I to sodium nitrite is from 1: 1 to 1: 1.5.
  • the solvent used in step 1) is one or more of acetone, tetrahydrofuran, water, toluene, xylene, hexane and cyclohexane.
  • the reaction temperature in step 1) is -10-10 ° C, and the reaction time is 1-10h.
  • the step 2) is specifically a mixed reaction of a compound having the formula (III), sodium methyl mercaptan and a base catalyst to obtain 2-chloro-6-methylthiotoluene having the formula (V).
  • the base catalyst is one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
  • the molar ratio of the compound III to the sodium methyl mercaptan is 1: (1-3).
  • the solvent of the reaction in step 2) is one or more of water, acetone, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, toluene, xylene, ethyl acetate and ether.
  • the temperature of the reaction in step 2) is 10-130 ° C, and the reaction time is 2-10h.
  • the reaction scheme of the 2-chloro-6-methylthiotoluene is specifically:
  • Step b
  • the molar ratio of Compound I to HCl is 1: 2-1: 5; the molar ratio of Compound I to Compound II is 1: 1-1: 1.5.
  • the reaction temperature is -10-10 ° C and the reaction time is 1-10h.
  • the base catalyst is selected from one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
  • the reaction solvent is one or more of water, acetone, tetrahydrofuran, water, toluene, xylene, hexane and cyclohexane.
  • the reaction solvent is one or more of water, dichloromethane, dichloroethane, chloroform, toluene, xylene, ethyl acetate and ether.
  • the molar ratio of compound III to compound IV is 1: 1-3.
  • the reaction temperature is 10-130 ° C, and the reaction time is 2-10 h.
  • step a the weight ratio of the reaction solvent to the compound I is 2-8: 1; in step b, the weight ratio of the reaction solvent to the compound III is 2-8: 1.
  • the method for preparing 2-chloro-6-methylthiotoluene provided by the present invention uses 2-chloro-6-aminotoluene as a reactant, avoiding the use of highly polar and highly toxic hexamethyl Phosphoryl triamine as a solvent has the disadvantage of greater safety risks, and also avoids the disadvantages of using sodium methyl mercaptan solid reagent ethyl chloroformate, which is unsafe in industrial production, and other organic reagents that are more harmful to the environment. Low cost, easy operation, less pollution, safety and environmental protection, etc., suitable for large-scale industrial production.
  • the method for preparing 2-chloro-6-methylthiotoluene provided by the present invention has fewer reaction steps, higher reaction yield, and more economical and environmentally friendly production.
  • the invention provides a method for preparing 2-chloro-6-methylthiotoluene, including:
  • the present invention converts a compound having the structure of formula (I) into a compound having the structure of formula (III); specifically, the compound of the structure of the formula (I), sodium nitrite, and an acid are mixed and reacted to obtain the formula (III) Structured compound; wherein the acid is preferably hydrochloric acid or sulfuric acid; the mass concentration of the hydrochloric acid or sulfuric acid is preferably 25 to 40% by weight, more preferably 30 to 35% by weight; the molar ratio of the compound I to the acid is preferably It is 1: 2 to 1: 5, and more preferably 1: 3 to 1: 4.
  • the molar ratio of the compound I to sodium nitrite is preferably 1: 1 to 1: 1.5, and more preferably 1: 1.1 to 1: 1.4;
  • the solvent of the reaction is preferably one or more of acetone, tetrahydrofuran, water, toluene, xylene, hexane and cyclohexane, more preferably water;
  • the reaction temperature is preferably -10 to 10 ° C,
  • the reaction time is more preferably -5 to 5 ° C, and the reaction time is preferably 1 to 10 hours, and more preferably 2 to 8 hours.
  • the present invention has no special requirements on the feeding order of the reaction, and those skilled in the art can select a suitable feeding order according to actual needs.
  • the present invention converts a compound of the formula (III) into 2-chloro-6-methylthiotoluene of the structure of the formula (V); this step is particularly preferably to convert the compound of the formula (III), methyl mercaptan
  • the sodium and base catalysts are mixed and reacted to obtain 2-chloro-6-methylthiotoluene having the structure of formula (V).
  • the reaction temperature is preferably -5 to 10 ° C.
  • the methyl mercaptan is added.
  • the concentration of the aqueous sodium methyl mercaptan solution is 15-30% by weight, more preferably 20-25% by weight.
  • the added alkali catalyst is an aqueous solution of an alkali catalyst, and the concentration of the aqueous solution of the alkali catalyst is 25-40% by weight. It is preferably 30 to 35% by weight;
  • the base catalyst is one or more of sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide, and more preferably one or two of sodium hydroxide and potassium hydroxide
  • the molar ratio of the compound III to the sodium methyl mercaptan is 1: (1-3), more preferably 1: (1.5 to 2);
  • the solvent of the reaction is preferably water, acetone, tetrahydrofuran, dichloromethane, One or more of dichloroethane, chloroform, toluene, xylene, ethyl acetate and ether, more preferably water And one or two of ethyl acetate;
  • the reaction temperature is preferably -5 to 50 ° C, more preferably 0 to 30 ° C, most preferably
  • reaction flow of the method for preparing 2-chloro-6-methylthiotoluene provided by the present invention is as follows:
  • Step b
  • step a the molar ratio of compound I to HCl is 1: 2-1: 5; the molar ratio of compound I to compound II is 1: 1 to 1: 1.5.
  • step a the reaction temperature is -10 to 10 ° C, and the reaction time is 1 to 10 h.
  • the base catalyst is selected from one or more of sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide.
  • the reaction solvent is one or more of water, acetone, tetrahydrofuran, water, toluene, xylene, hexane, and cyclohexane.
  • the reaction solvent is one or more of water, acetone, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, toluene, xylene, ethyl acetate, and ether.
  • step b the molar ratio of compound III to compound IV is 1: 1-3.
  • step b the reaction temperature is -10 to 60 ° C and the reaction time is 2 to 10 h.
  • step a the weight ratio of the reaction solvent to the compound I is 2 to 8: 1; in step b, the weight ratio of the reaction solvent to the compound III is 2 to 8: 1, respectively.
  • the beneficial effects of the present invention are as follows: the method for preparing 2-chloro-6-methylthiotoluene provided by the present invention, and 2-chloro-6-aminotoluene as a reactant, avoiding the use of highly polar and highly toxic hexamethylphosphorus Acyltriamine is a solvent, which has the disadvantage of greater safety risks. At the same time, it avoids the disadvantages of using sodium methyl mercaptan solid reagent ethyl chloroformate and other organic reagents which are more harmful to the environment in industrial production, and has a cost. Low, easy to operate, less pollution, safe and environmentally friendly, suitable for large-scale industrial production.
  • the method for preparing 2-chloro-6-methylthiotoluene provided by the present invention has fewer reaction steps, higher reaction yield, and more economical and environmentally friendly production.
  • Step a Add 30% hydrochloric acid (182g, 1.49mol) and water to the reaction flask, and dropwise add 53g of 2-chloro-6-aminotoluene, and control the temperature below 50 ° C. After the addition is complete, stir for 10 minutes and cool to At -5-10 ° C, add the prepared sodium nitrite (90.25g, 0.52mol) solution dropwise, add it in about 2 hours, the temperature does not exceed 10 ° C, continue to stir for 30 minutes, store at about 0 ° C, and reserve.
  • Step b Add a 20 wt% aqueous solution of sodium methyl mercaptan (184.7 g, 0.53 mol) into another reaction bottle, cool to about 0 ° C, add a 30 wt% aqueous solution of sodium hydroxide (23.3 g, 0.17 mol), and stir until all Dissolve, start to add the cold diazo solution dropwise, and control the temperature not to exceed 10 ° C. After the dropwise addition is completed in about 2 hours, remove the ice bath, continue stirring for 4 hours, add toluene, remove the freezing, continue to stir for 2 hours, and warm to 30 ° C Layered and washed once. Desolvate to 110-115 ° C under reduced pressure to obtain 59.5 g of a dark red liquid with a GC normalized content of 98.6% or more and a yield of 94%, which can be directly used in the next reaction.
  • Step a Add 30% dilute sulfuric acid (244g, 0.75mol) and water to the reaction bottle, and dropwise add 53g of 2-chloro-6-aminotoluene, and control the temperature below 40 ° C. After the dropwise addition, stir for 10 minutes and cool down To -10-10 ° C, add the prepared sodium nitrite (90.25g, 0.52mol) solution dropwise, add it in about 2 hours, the temperature does not exceed 10 ° C, continue to stir for 1 hour, store at about 0 ° C, and reserve.
  • Step b Add a 20% aqueous solution of sodium methyl mercaptan (184.7g, 0.53mol) to another reaction bottle, cool to about 3 ° C, add a 30% aqueous solution of sodium carbonate (18.2g, 0.17mol), and stir until all is dissolved Start to add the cold diazo solution dropwise, and control the temperature not to exceed 10 °C. After the dropwise addition is completed in about 2 hours, remove the ice bath, continue stirring for 4 hours, add toluene, remove the freezing, continue stirring for 2 hours, and raise the temperature to about 30 ° C. Layer, washed once. Desolvate to 110-115 ° C under reduced pressure to obtain 60.2 g of a dark red liquid with a GC content of 98.5% and a yield of 95%, which can be directly used in the next reaction.
  • Step a Add 30% hydrochloric acid (182g, 1.49mol) and water to the reaction flask, and dropwise add 53g of 2-chloro-6-aminotoluene, and control the temperature below 50 ° C. After the addition is complete, stir for 10 minutes and cool to At -5-10 ° C, add the prepared sodium nitrite (90.25g, 0.52mol) solution dropwise, add it in about 2 hours, the temperature does not exceed 10 ° C, continue to stir for 30 minutes, store at about 0 ° C, and reserve.
  • Step b Add 20% sodium methyl mercaptan (184.7g, 0.53mol) aqueous solution to another reaction bottle, cool to about 0 ° C, add 30% potassium carbonate (23.5g, 0.17mol), and stir until all dissolve. Start to add the cold diazo solution, and control the temperature not to exceed 10 °C. After the addition is completed in about 2 hours, remove the ice bath, continue stirring for 4 hours, add dichloromethane, remove the freezing, continue to stir for 2 hours, and raise the temperature to about 30 °C Layered and washed once. Desolvate to 50-60 ° C under reduced pressure to obtain 58 g of a dark red liquid with a GC content of 97% and a yield of 93%, which can be directly used in the next reaction.
  • Step a Add 30% sulfuric acid (244g, 0.75mol) and water to the reaction bottle, and dropwise add 53g of 2-chloro-6-aminotoluene, and control the temperature below 40 ° C. After the dropwise addition is complete, stir for 10 minutes and cool to At -5-10 ° C, add the prepared sodium nitrite (90.25g, 0.52mol) solution dropwise, add it in about 2 hours, the temperature does not exceed 10 ° C, continue to stir for 30 minutes, store at about 0 ° C, and reserve.
  • Step b Add a 20% aqueous solution of sodium methyl mercaptan (184.7g, 0.53mol) to another reaction bottle, lower the temperature to about 0 ° C, add a 30% potassium hydroxide (9.6g, 0.17mol) aqueous solution, and stir until all Dissolve, start to add the cold diazo solution dropwise, and control the temperature not to exceed 10 °C. After the dropwise addition is completed in about 2 hours, remove the ice bath, continue stirring for 4 hours, add ethyl acetate, remove the freeze, continue stirring for 2 hours, and warm to 30. Layered around °C, washed once with water. Desolvate to 60-65 ° C under reduced pressure to obtain 61 g of a dark red liquid with a GC content of 97% and a yield of 96%, which can be directly used in the next reaction.

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Abstract

本发明公开了一种2-氯-6-甲硫基甲苯的制备方法，该方法采用2-氯-6-氨基甲苯和甲硫醇钠水溶液为原料经重氮化生成2-氯-6-甲硫基甲苯。本发明提供的2-氯-6-甲硫基甲苯的制备方法，克服了传统合成方法中用2，6-二氯甲苯为原料及高极性高毒性的六甲基磷酰三胺为溶剂以及对环境危害大且使用不方便甲硫醇钠固体试剂的缺点；同时也解决了传统方法合成2-氯-6-甲硫基甲苯中六甲基磷酰三胺溶剂难回收，成本高、环境污染大等难题，具有成本低、易操作、污染少、安全环保等优点，适合大规模工业化生产。

Description

一种2-氯-6-甲硫基甲苯的制备方法
本申请要求于2018年8月10日提交中国专利局、申请号为201810913577.x、发明名称为“一种2-氯-6-甲硫基甲苯的制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及有机化工技术领域，具体涉及一种2-氯-6-甲硫基甲苯的制备方法。
背景技术
环磺酮是活性较高、用量较少，且比较安全的一类新型三酮类除草剂，2-氯-6-甲硫基甲苯是生产环磺酮的关键中间体，国外专利(US6211216B)中报道的合成方法是用2，6-二氯甲苯为原料及强极性高毒性的六甲基磷酰三胺为溶剂，该方法对环境危害大且使用了在工业生产上不安全的甲硫醇钠固体；传统方法合成2-氯-6-甲硫基甲苯中六甲基磷酰三胺溶剂难回收，成本高、环境污染大；具有成本高、不易操作、污染大、安全风险大，不环保等缺点，不适合大规模工业化生产。
发明内容
针对上述现有技术中存在的缺陷，本发明所要解决的技术问题是提供一种2-氯-6-甲硫基甲苯的制备方法，该方法反应步骤少，成本低、易操作、污染少，适合大规模工业化生产要求的2-氯-6-甲硫基甲苯的制备。
本发明提供了一种2-氯-6-甲硫基甲苯的制备方法，包括：
1)将式(I)结构的化合物转化为式(III)结构的化合物；
Figure PCTCN2019094294-appb-000001
2)将式(III)结构的化合物转化为式(V)结构的2-氯-6-甲硫基甲 苯；
Figure PCTCN2019094294-appb-000002
优选的，所述步骤1)具体为：将式(I)结构的化合物、亚硝酸钠和酸混合反应，得到式(III)结构的化合物；
其中，所述酸为盐酸或硫酸。
优选的，所述化合物I与所述酸的摩尔比为1∶2～1∶5；
所述化合物I与亚硝酸钠的摩尔比为1∶1～1∶1.5。
优选的，步骤1)反应的溶剂为丙酮、四氢呋喃、水、甲苯、二甲苯、己烷和环己烷中的一种或几种。
优选的，步骤1)反应的温度为-10-10℃，反应时间为1-10h。
优选的，所述步骤2)具体为将式(III)结构的化合物、甲硫醇钠和碱催化剂混合反应，得到式(V)结构的2-氯-6-甲硫基甲苯。
优选的，所述碱催化剂为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种或几种。
优选的，所述化合物III与所述甲硫醇钠的摩尔比为1∶(1-3)。
优选的，所述步骤2)反应的溶剂为水、丙酮、四氢呋喃、二氯甲烷、二氯乙烷、氯仿、甲苯、二甲苯、乙酸乙酯和乙醚中的一种或几种。
优选的，所述步骤2)反应的温度为10-130℃，反应时间为2-10h。优选的，所述2-氯-6-甲硫基甲苯的反应流程具体为：
步骤a：
Figure PCTCN2019094294-appb-000003
步骤b：
Figure PCTCN2019094294-appb-000004
优选的，步骤a中，化合物I与HCl的摩尔比为1∶2-1∶5；化合物I与化合物II的摩尔比为1∶1-1∶1.5。
优选的，步骤a中，反应温度为-10-10℃，反应时间为1-10h。
优选的，所述碱催化剂选自为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种或几种。
优选的，步骤a中，反应溶剂为水、丙酮、四氢呋喃、水、甲苯、二甲苯、己烷和环己烷中的一种或几种。
优选的，步骤b中，反应溶剂为水、二氯甲烷、二氯乙烷、氯仿、甲苯、二甲苯、乙酸乙酯和乙醚中的一种或几种。
优选的，步骤b中，化合物III与化合物IV的摩尔比为1∶1-3。
优选的，步骤b中，反应温度为10-130℃，反应时间为2-10h。
优选的，步骤a中，反应溶剂与化合物I的重量比分别为2-8∶1；步骤b中，反应溶剂与化合物III的重量比分别为2-8∶1。
与现有技术相比，本发明提供的2-氯-6-甲硫基甲苯的制备方法，以2-氯-6-氨基甲苯作为反应物，避免了使用强极性高毒性的六甲基磷酰三胺为溶剂，存在较大安全隐患的缺点，同时也避免了使用在工业生产上不安 全的甲硫醇钠固体试剂氯甲酸乙酯及其他对环境危害较大有机试剂的缺点，具有成本低、易操作、污染少、安全环保等优点，适合大规模工业化生产。且本发明提供的2-氯-6-甲硫基甲苯的制备方法，反应步骤少，反应收率较高，生产更经济环保。
具体实施方式
为了使本领域的技术人员更好地理解发明的技术方案，下面结合具体实施方式对本发明作进一步的详细说明。
本发明提供了一种2-氯-6-甲硫基甲苯的制备方法，包括：
1)将式(I)结构的化合物转化为式(III)结构的化合物；
Figure PCTCN2019094294-appb-000005
2)将式(III)结构的化合物转化为式(V)结构的2-氯-6-甲硫基甲苯；
Figure PCTCN2019094294-appb-000006
按照本发明，本发明将式(I)结构的化合物转化为式(III)结构的化合物；具体优选为：将式(I)结构的化合物、亚硝酸钠和酸混合反应，得到式(III)结构的化合物；其中，所述酸优选为盐酸或硫酸；所述盐酸或硫酸的质量浓度优选为25～40wt％，更优选为30～35wt％；所述化合物I与所述酸的摩尔比优选为1∶2～1∶5，更优选为1∶3～1∶4；所述化合物I与亚硝酸钠的摩尔比优选为1∶1～1∶1.5，更优选为1∶1.1～1∶1.4；所述反应的溶 剂优选为丙酮、四氢呋喃、水、甲苯、二甲苯、己烷和环己烷中的一种或几种，更优选为水；反应的温度优选为-10～10℃，更优选为-5～5℃，反应时间优选为1～10h，更优选为2～8小时；本发明对反应的加料顺序没有特殊要求，本领域技术人员可以根据实际需要选择合适的加料顺序。
按照本发明，本发明将式(III)结构的化合物转化为式(V)结构的2-氯-6-甲硫基甲苯；该步骤具体优选为将式(III)结构的化合物、甲硫醇钠和碱催化剂混合反应，得到式(V)结构的2-氯-6-甲硫基甲苯；其中，原料混合时，反应温度优选为-5～10℃，混合时，加入的为甲硫醇钠的水溶液，所述甲硫醇钠水溶液的浓度为15～30wt％，更优选为20～25wt％，加入的碱催化剂为碱催化剂水溶液，所述碱催化剂水溶液的浓度为25～40wt％，更优选为30～35wt％；所述碱催化剂为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种或几种，更优选为氢氧化钠和氢氧化钾中的一种或两种；所述化合物III与所述甲硫醇钠的摩尔比为1∶(1-3)，更优选为1∶(1.5～2)；反应的溶剂优选为水、丙酮、四氢呋喃、二氯甲烷、二氯乙烷、氯仿、甲苯、二甲苯、乙酸乙酯和乙醚中的一种或几种，更优选为水和乙酸乙酯中的一种或两种；反应的温度优选为-5～50℃，更优选为0～30℃，最优选为5～20℃，反应时间优选为2～10h，更优选为3～8小时；
具体的，本发明提供的2-氯-6-甲硫基甲苯的制备方法的反应流程如下：
步骤a：
Figure PCTCN2019094294-appb-000007
步骤b：
Figure PCTCN2019094294-appb-000008
进一步改进在于，步骤a中，化合物I与HCl的摩尔比为1∶2-1∶5；化合物I与化合物II的摩尔比为1∶1～1∶1.5。
进一步改进在于，步骤a中，反应温度为-10～10℃，反应时间为1～10h。
进一步改进在于，步骤b中，所述碱催化剂选自为碳酸钠、碳酸钾、氢氧化钠、氢氧化钾中的一种或几种。
进一步改进在于，步骤a中，反应溶剂为水、丙酮、四氢呋喃、水、甲苯、二甲苯、己烷、环己烷中的一种或几种。
进一步改进在于，步骤b中，反应溶剂为水、丙酮、四氢呋喃、二氯甲烷、二氯乙烷、氯仿、甲苯、二甲苯、乙酸乙酯、乙醚中的一种或几种。
进一步改进在于，步骤b中，化合物III与化合物IV的摩尔比为1∶1-3。
进一步改进在于，步骤b中，反应温度为-10～60℃，反应时间为2～10h。
进一步改进在于，步骤a中，反应溶剂与化合物I的重量比分别为2～8∶1；步骤b中，反应溶剂与化合物III的重量比分别为2～8∶1。
本发明的有益效果在于：本发明提供的2-氯-6-甲硫基甲苯的制备方法，2-氯-6-氨基甲苯作为反应物，避免了使用强极性高毒性的六甲基磷酰三胺为溶剂，存在较大安全隐患的缺点，同时也避免了使用在工业生产上不安全的甲硫醇钠固体试剂氯甲酸乙酯及其他对环境危害较大有机试剂的缺点，具有成本低、易操作、污染少、安全环保等优点，适合大规模工业化生产。
另外，本发明提供的2-氯-6-甲硫基甲苯的制备方法，反应步骤少， 反应收率较高，生产更经济环保。
以上是对发明内容的详细分析，下面结合实施例对本申请作进一步详细描述，有必要在此指出的是，以下具体实施方式只用于对本申请进行进一步的说明，不能理解为对本申请保护范围的限制，该领域的技术人员可以根据上述申请内容对本申请作出一些非本质的改进和调整。
实施例1
步骤a：将30％盐酸(182g，1.49mol)和水加入到反应瓶中，滴加2-氯-6-氨基甲苯53g，控制温度在50℃以下，滴加完毕，搅拌10分钟，降温至-5-10℃，滴加配制好的亚硝酸钠(90.25g，0.52mol)溶液，约2小时内加毕，温度不超过10℃，继续搅拌30分钟，于0℃左右保存、备用。
步骤b：将20wt％甲硫醇钠(184.7g，0.53mol)水溶液加入到另一反应瓶中，降温至0℃左右，加入30wt％氢氧化钠(23.3g，0.17mol)水溶液，搅拌至全部溶解，开始滴加冷的重氮液，控制温度不超过10℃，约2小时滴加完毕，撤去冰浴，继续搅拌4小时，加入甲苯，撤去冷冻，继续搅拌2小时，升温至30℃左右分层，水洗一次性。减压脱溶至110-115℃，得到深红色液体59.5g，GC归一含量98.6％以上，收率94％，可直接用于下步反应。
实施例2
步骤a：将30％稀硫酸(244g，0.75mol)和水加入到反应瓶中，滴加2-氯-6-氨基甲苯53g，控制温度在40℃以下，滴加完毕，搅拌10分钟，降温至-10-10℃，滴加配制好的亚硝酸钠(90.25g，0.52mol)溶液，约2小时内加毕，温度不超过10℃，继续搅拌1小时，于0℃左右保存、备用。
步骤b：将20％甲硫醇钠(184.7g，0.53mol)水溶液加入到另一反应瓶中，降温至3℃左右，加入30％碳酸钠(18.2g，0.17mol)水溶液，搅拌至全部溶解，开始滴加冷的重氮液，控制温度不超过10℃，约2小时滴加完毕，撤去冰浴，继续搅拌4小时，加入甲苯，撤去冷冻，继续搅拌2小时，升温至30℃左右分层，水洗一次性。减压脱溶至110-115℃，得到深红色液体60.2g，GC含量98.5％，收率95％，可直接用于下步反应。
实施例3
步骤a：将30％盐酸(182g，1.49mol)和水加入到反应瓶中，滴加2-氯-6-氨基甲苯53g，控制温度在50℃以下，滴加完毕，搅拌10分钟，降温至-5-10℃，滴加配制好的亚硝酸钠(90.25g，0.52mol)溶液，约2小时内加毕，温度不超过10℃，继续搅拌30分钟，于0℃左右保存、备用。
步骤b：将20％甲硫醇钠(184.7g，0.53mol)水溶液加入到另一反应瓶中，降温至0℃左右，加入30％碳酸钾(23.5g，0.17mol)，搅拌至全部溶解，开始滴加冷的重氮液，控制温度不超过10℃，约2小时滴加完毕，撤去冰浴，继续搅拌4小时，加入二氯甲烷，撤去冷冻，继续搅拌2小时，升温至30℃左右分层，水洗一次性。减压脱溶至50-60℃，得到深红色液体58g，GC含量97％，收率93％，可直接用于下步反应。
实施例4
步骤a：将30％硫酸(244g，0.75mol)和水加入到反应瓶中，滴加2-氯-6-氨基甲苯53g，控制温度在40℃以下，滴加完毕，搅拌10分钟，降温至-5-10℃，滴加配制好的亚硝酸钠(90.25g，0.52mol)溶液，约2小时内加毕，温度不超过10℃，继续搅拌30分钟，于0℃左右保存、备用。
步骤b：将20％甲硫醇钠(184.7g，0.53mol)水溶液加入到另一反应瓶中，降温至0℃左右，加入30％氢氧化钾(9.6g，0.17mol)水溶液，搅拌至全部溶解，开始滴加冷的重氮液，控制温度不超过10℃，约2小时滴加完毕，撤去冰浴，继续搅拌4小时，加入乙酸乙酯，撤去冷冻，继续搅拌2小时，升温至30℃左右分层，水洗一次性。减压脱溶至60-65℃，得到深红色液体61g，GC含量97％，收率96％，可直接用于下步反应。
以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出，对于本技术领域技术人员来说，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这些改进和修饰也落入本发明权利要求的保护范围内。

Claims (19)

  1. 一种2-氯-6-甲硫基甲苯的制备方法，包括：
    1)将式(I)结构的化合物转化为式(III)结构的化合物；
    Figure PCTCN2019094294-appb-100001
    2)将式(III)结构的化合物转化为式(V)结构的2-氯-6-甲硫基甲苯；
    Figure PCTCN2019094294-appb-100002
  2. 根据权利要求1所述的制备方法，其特征在于，所述步骤1)具体为：将式(I)结构的化合物、亚硝酸钠和酸混合反应，得到式(III)结构的化合物；
    其中，所述酸为盐酸或硫酸。
  3. 根据权利要求2所述的制备方法，其特征在于，所述化合物I与所述酸的摩尔比为1∶2～1∶5；
    所述化合物I与亚硝酸钠的摩尔比为1∶1～1∶1.5。
  4. 根据权利要求1所述的制备方法，其特征在于，步骤1)反应的溶剂为丙酮、四氢呋喃、水、甲苯、二甲苯、己烷和环己烷中的一种或几种。
  5. 根据权利要求1所述的制备方法，其特征在于，步骤1)反应的温度为-10～10℃，反应时间为1～10h。
  6. 根据权利要求1所述的制备方法，其特征在于，所述步骤2)具体为将式(III)结构的化合物、甲硫醇钠和碱催化剂混合反应，得到式(V)结构的2-氯-6-甲硫基甲苯。
  7. 根据权利要求6所述的制备方法，其特征在于，所述碱催化剂为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种或几种。
  8. 根据权利要求6所述的制备方法，其特征在于，所述化合物III与所述甲硫醇钠的摩尔比为1∶(1～3)。
  9. 根据权利要求1所述的制备方法，其特征在于，所述步骤2)反应的溶剂为水、丙酮、四氢呋喃、二氯甲烷、二氯乙烷、氯仿、甲苯、二甲苯、乙酸乙酯和乙醚中的一种或几种。
  10. 根据权利要求1所述的制备方法，其特征在于，所述步骤2)反应的温度为-5～50℃，反应时间为2～10h。
  11. 根据权利要求1所述的制备方法，其特征在于，所述2-氯-6-甲硫基甲苯的反应流程具体为：
    步骤a：
    Figure PCTCN2019094294-appb-100003
    步骤b：
    Figure PCTCN2019094294-appb-100004
  12. 根据权利要求11所述的制备方法，其特征在于，步骤a中，化合物I与HCl的摩尔比为1∶2-1∶5；化合物I与化合物II的摩尔比为1∶1-1∶1.5。
  13. 根据权利要求11所述的制备方法，其特征在于：步骤a中，反应温度为-10～10℃，反应时间为1～10h。
  14. 根据权利要求11所述的制备方法，其特征在于：步骤b中，所述碱催化剂选自为碳酸钠、碳酸钾、氢氧化钠和氢氧化钾中的一种或几种。
  15. 根据权利要求11所述的制备方法，其特征在于：步骤a中，反应溶剂为丙酮、四氢呋喃、水、甲苯、二甲苯、己烷和环己烷中的一种或几种。
  16. 根据权利要求11所述的制备方法，其特征在于：步骤b中，反应溶剂为水、丙酮和四氢呋喃中的一种或几种。
  17. 根据权利要求11所述的制备方法，其特征在于：步骤b中，化合物III与化合物IV的摩尔比为1∶(1～3)。
  18. 根据权利要求11所述的制备方法，其特征在于：步骤b中，反应温度为-10～60℃，反应时间为2～10h。
  19. 根据权利要求11所述的制备方法，其特征在于：步骤a中，反应溶剂与化合物I的重量比分别为(2～8)∶1；步骤b中，反应溶剂与化合物III的重量比分别为(2～8)∶1。
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