阅读说明：本技术 一种制备4-氯-3,5-二甲基苯酚的方法 (Method for preparing 4-chloro-3, 5-dimethylphenol ) 是由 王加琦 袁帅 丰茂英 卢福广 曹娜 丛鑫 刘振峰 刘超 黄少峰 崔乾 余炎冰 于 2020-04-28 设计创作，主要内容包括：本发明公开了一种制备4-氯-3,5-二甲基苯酚的方法。所述方法是以光气为氯化试剂,以饱和氮氧杂环化合物为促进剂,由3,5-二甲基苯酚进行氯化反应得到4-氯-3,5-二甲基苯酚。本发明所述方法具有无气体硫化物产生、对位选择性高、操作简便等优点。(The invention discloses a method for preparing 4-chloro-3, 5-dimethylphenol. The method takes phosgene as a chlorination reagent and a saturated nitrogen-oxygen heterocyclic compound as an accelerating agent to carry out chlorination reaction on 3, 5-dimethylphenol to obtain the 4-chloro-3, 5-dimethylphenol. The method has the advantages of no generation of gas sulfide, high para-position selectivity, simple and convenient operation and the like.)

1. The method for preparing 4-chloro-3, 5-dimethylphenol is characterized in that phosgene is used as a chlorination reagent, a saturated nitrogen-oxygen heterocyclic compound is used as an accelerating agent, and chlorination reaction is carried out on 3, 5-dimethylphenol to obtain the 4-chloro-3, 5-dimethylphenol.

2. The method of claim 1, wherein the saturated nitroxide compound has the structure of formula I,

in the formula (I), the compound is shown in the specification,the heterocyclic ring is a saturated multi-element heterocyclic ring containing nitrogen and oxygen atoms, the number of ring-forming atoms of the saturated multi-element heterocyclic ring is not less than 5, preferably 5-18, and more preferably the saturated multi-element heterocyclic ring is a saturated six-element heterocyclic ring;

r is selected from substituted or unsubstituted alkyl and cycloalkyl, preferably C1-6 alkyl or cycloalkyl; more preferably, the substituted alkyl and cycloalkyl have substituents selected from alkoxy and chlorine.

3. The method of claim 1 or 2, wherein the saturated nitroxide compound is a substituted morpholine derivative having the structure shown in formula II,

in the formula, R is selected from substituted or unsubstituted alkyl and cycloalkyl, preferably C1-6 alkyl or cycloalkyl; preferably, the substituted alkyl and cycloalkyl have substituents selected from alkoxy and chlorine.

4. A process according to any one of claims 1 to 3, wherein the saturated nitroxide compound is one or more of N-methylmorpholine, N-ethylmorpholine, 4-cyclopentylmorpholine, 4-cyclohexylmorpholine, 4- (2-methoxyethyl) morpholine, 4- (cyclohexylmethyl) morpholine, 4- (2-chloroethyl) morpholine, further preferably N-methylmorpholine, 4-cyclopentylmorpholine, 4-cyclohexylmorpholine, 4- (cyclohexylmethyl) morpholine.

5. The method according to any one of claims 1 to 4, wherein the molar ratio of the phosgene to the 3, 5-dimethylphenol is (1-3): 1, preferably (2-3): 1;

preferably, the charging time of the phosgene is controlled to be 0.5-2 hours, preferably 0.5-1 hour; the feeding time of the 3, 5-dimethylphenol is controlled to be 0.5-2 hours, preferably 0.5-1 hour, and preferably the 3, 5-dimethylphenol and phosgene are fed simultaneously.

6. A process according to any one of claims 1 to 5, wherein the promoter is used in an amount of 0.5 to 20 wt%, preferably 0.5 to 5 wt%, more preferably 1 to 2.5 wt% of the 3, 5-dimethylphenol.

7. The method according to any one of claims 1 to 6, wherein the chlorination reaction is carried out at a temperature of 30 to 120 ℃, preferably 80 to 100 ℃; the reaction time is 2-8 h, preferably 2-5 h; the reaction pressure is less than or equal to 5MPaA, and the normal pressure is preferred.

8. The process according to any one of claims 1 to 7, wherein the atmosphere of the chlorination reaction gas is an inert gas, preferably nitrogen or argon.

9. The process according to any one of claims 1 to 8, wherein the chlorination reaction is carried out in the presence of a solvent selected from 1, 2-dichloroethane, one or more of dichloromethane, chloroform, tetrachloroethylene, preferably tetrachloroethylene;

preferably, the solvent is used in an amount of 20 to 300 wt%, preferably 150 to 250 wt%, of the 3, 5-dimethylphenol;

preferably, the solvent is divided into two parts and added into a chlorination reaction system, wherein one part is mixed with 3, 5-dimethylphenol and a saturated nitrogen-oxygen heterocyclic compound to prepare a solution; the other part is directly added into the reaction kettle; more preferably, the ratio of the two parts of solvent is (0.2-2): 1, preferably (0.5 to 1): 1.

10. the method according to any one of claims 1 to 9, wherein the chlorination reaction further comprises crystallization and filtration operations after completion of the chlorination reaction.

Technical Field

The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for preparing 4-chloro-3, 5-dimethylphenol.

Background

4-chloro-3, 5-dimethylphenol (parachlorometaxylenol, PCMX) is a high-efficiency broad-spectrum mildew-proof antibacterial agent and is widely applied in the fields of daily use, medical use, industrial sterilization and the like. With the banning of triclosan and triclocarban and the increase of the living quality of people to the increase of the sterilization demand, 4-chloro-3, 5-dimethylphenol has a greater use demand.

4-chloro-3, 5-dimethylphenol is obtained by chlorinating 3, 5-dimethylphenol, when chlorine is used as a chlorinating agent, the P/O ratio of a para-substitution product 4-chloro-3, 5-dimethylphenol (PCMX) to an ortho-substitution product 2-chloro-3, 5-dimethylphenol (OCMX) is only 1.5, and when sulfuryl chloride is used, the reaction effect of P/O >6 can be achieved, and the method is mostly used in industry at present, but the byproduct also contains sulfur dioxide besides hydrogen chloride, thereby bringing troubles to the post-treatment of three wastes. US patent 4245127 also describes the use of organic sulphides and metal chlorides as co-catalysts, with a PCMX yield of 91.5%, a P/O value of 14.4 and a not high para-selectivity.

Wufei introduces a method of using hydrochloric acid as a chlorination reagent and copper chloride as a catalyst in the text of 'technical research on synthesizing 4-chloro-3, 5-xylenol by oxidizing and chlorinating 3, 5-dimethylphenol', the PCMX selectivity can reach 95.47%, and the P/O ratio is 31.40; the method has certain control on reaction byproducts, but relates to heterogeneous reaction, and has certain influence on mass transfer of the reaction.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provide a method for preparing 4-chloro-3, 5-dimethylphenol by chlorinating 3, 5-dimethylphenol with high selectivity under the synergistic chlorination catalysis of phosgene and saturated nitrogen-oxygen heterocycle. The method has the characteristics of no generation of gas sulfide, high para-position selectivity, simple and convenient operation and the like.

In order to achieve the above purpose, the invention adopts the following technical scheme:

a method for preparing 4-chloro-3, 5-dimethylphenol is characterized in that phosgene is used as a chlorination reagent, a saturated nitrogen-oxygen heterocyclic compound is used as an accelerating agent, and chlorination reaction is carried out on 3, 5-dimethylphenol to obtain the 4-chloro-3, 5-dimethylphenol.

In the method, the saturated nitrogen-oxygen heterocyclic compound has a structure shown in a formula I,

in the formula (I), the compound is shown in the specification,the heterocyclic ring is a saturated multi-element heterocyclic ring containing nitrogen and oxygen atoms, the number of ring-forming atoms of the saturated multi-element heterocyclic ring is not less than 5, and preferably, the number of ring-forming atoms is 5-18; more preferably the saturated multinary heterocycle is a saturated six-membered ring;

r is selected from substituted or unsubstituted alkyl and cycloalkyl, preferably C1-6 alkyl or cycloalkyl; more preferably, the substituted alkyl and cycloalkyl have substituents selected from alkoxy and chlorine.

Preferably, the saturated nitrogen-oxygen heterocyclic compound is a substituted morpholine derivative and has a structure shown in a formula II,

wherein R is the same as R in formula I; the method comprises the following specific steps: selected from substituted or unsubstituted alkyl and cycloalkyl, preferably C1-6 alkyl or cycloalkyl; preferably, the substituted alkyl and cycloalkyl have substituents selected from alkoxy and chlorine.

Further preferably, the saturated nitrogen-oxygen heterocyclic compound is one or more of N-methylmorpholine, N-ethylmorpholine, 4-cyclopentylmorpholine, 4-cyclohexylmorpholine, 4- (2-methoxyethyl) morpholine, 4- (cyclohexylmethyl) morpholine, 4- (2-chloroethyl) morpholine, further preferably N-methylmorpholine, 4-cyclopentylmorpholine, 4-cyclohexylmorpholine, 4- (cyclohexylmethyl) morpholine.

In the method, the molar ratio of the phosgene usage amount to the 3, 5-dimethylphenol is (1-3): 1, preferably (2-3): 1;

preferably, during the chlorination reaction, after the temperature is raised to the reaction temperature, the feeding rate needs to be controlled, and phosgene and 3, 5-dimethylphenol are slowly fed in;

further preferably, the charging time of the phosgene is controlled to be 0.5-2 hours, preferably 0.5-1 hour;

the feeding time of the 3, 5-dimethylphenol is controlled to be 0.5-2 hours, preferably 0.5-1 hour, and preferably the 3, 5-dimethylphenol and phosgene are fed simultaneously.

In the method of the invention, the amount of the promoter is 0.5-20 wt%, preferably 0.5-5 wt%, and more preferably 1-2.5 wt% of 3, 5-dimethylphenol.

In the method, the chlorination reaction is carried out at the reaction temperature of 30-120 ℃, preferably 80-100 ℃; the reaction time is 2-8 h, preferably 2-5 h; the reaction pressure is less than or equal to 5MPaA, and the normal pressure, namely 0.1MPaA is preferred.

Preferably, the atmosphere of the chlorination reaction gas is an inert gas, preferably nitrogen or argon.

In the method, the chlorination reaction is carried out in the presence of a solvent, wherein the solvent is selected from one or more of 1, 2-dichloroethane, dichloromethane, chloroform and tetrachloroethylene, and preferably tetrachloroethylene;

preferably, the solvent is used in an amount of 20 to 300 wt%, preferably 150 to 250 wt%, based on the weight of 3, 5-dimethylphenol.

Preferably, the solvent is divided into two parts and added into a chlorination reaction system, wherein one part is mixed with 3, 5-dimethylphenol and a saturated nitrogen-oxygen heterocyclic compound to prepare a solution; the other part is directly added into the reaction kettle; more preferably, the ratio of the two parts of solvent is (0.2-2): 1, preferably (0.5 to 1): 1, most preferably 1: 1.

in the method, after the chlorination reaction is finished, the method further comprises a post-treatment operation, wherein the post-treatment is a conventional operation method, does not need to be specific, and preferably comprises conventional operation methods such as crystallization, filtration and the like.

The method specifically comprises the following steps in some preferred examples: dissolving 3, 5-dimethylphenol and a promoter saturated nitrogen-oxygen heterocyclic compound in a part of solvent to obtain a 3, 5-dimethylphenol solution; and putting the other part of the solvent into a reaction kettle, heating to the reaction temperature of 30-120 ℃, slowly introducing phosgene and a 3, 5-dimethylphenol solution within 0.5-2 h, stirring to perform chlorination reaction for 2-8 h, stopping the reaction after the target conversion rate is reached, and cooling, crystallizing and filtering the reaction solution to obtain the 4-chloro-3, 5-dimethylphenol.

In the method, after the chlorination reaction is finished, a tail gas separation and recovery device is also arranged so as to conveniently recover and use unreacted phosgene, CO, HCl and other byproducts.

The research of the invention finds that in the method for preparing 4-chloro-3, 5-dimethylphenol by chlorination reaction, when phosgene is used as a chlorinating reagent alone, the chlorination effect is not ideal, after a saturated nitrogen-oxygen heterocyclic compound is introduced as an accelerating agent, nitrogen or oxygen atoms of the saturated nitrogen-oxygen heterocyclic compound and phenolic hydroxyl form intermolecular hydrogen bonds, on one hand, carbonyl of the phosgene is difficult to generate hydrogen bonds with the phenolic hydroxyl, and the chlorination performance of the phosgene is improved, on the other hand, the adjacent position of the 3, 5-dimethylphenol has larger steric hindrance and is difficult to participate in the chlorination reaction, hydrogen at the para position of the 3, 5-dimethylphenol is easier to be chlorinated, and the synergistic effect of the phosgene and nitrogen oxide obviously improves the chlorination efficiency and the para position selectivity of the 3, 5-dimethylphenol.

The invention has the beneficial effects that:

the method takes phosgene as a chlorination reagent, and avoids the generation of gas sulfide compared with the traditional method; the synergistic effect of phosgene and saturated nitrogen-oxygen heterocyclic accelerant obviously improves the chlorination efficiency and the para-position selectivity, the conversion rate of the raw material 3, 5-dimethylphenol can reach more than 97 percent, and the para-position chlorination selectivity is more than 96 percent. The method has the characteristics of environmental friendliness, high para-selectivity and the like, and has an industrial prospect.

Detailed Description

The method according to the invention will be further illustrated by the following examples, but the invention is not limited to the examples listed, but also encompasses any other known modification within the scope of the claims of the invention.

The conversion of 3, 5-dimethylphenol and the selectivity of 4-chloro-3, 5-dimethylphenol were determined by gas chromatography:

gas chromatograph: agilent 7890; a chromatographic column: DB-5; sample inlet temperature: 280 ℃; the split ratio is 10: 1; h₂：Air：N₂40: 400: 30(mL/min) column flow rate 5.0 mL/min; temperature rising procedure: keeping the temperature at 50 ℃ for 2min, heating from 50 ℃ to 280 ℃ at the speed of 15 ℃/min, and keeping the temperature at 280 ℃ for 5 min; FID detector temperature: 280 ℃.

The P/O ratio is calculated as follows: W/O-W1/W2, W1 indicates the content (wt%) of 4-chloro-3, 5-dimethylphenol (PCMX), and W2 indicates the content (wt%) of 2-chloro-3, 5-dimethylphenol (OCMX).

Reagent information: 3, 5-dimethylphenol (99%) was purchased from carbofuran technologies; dichloromethane, chloroform, tetrachloroethylene (99%) were purchased from mclin biochemistry; n-methylmorpholine, 4- (2-methoxyethyl) morpholine, 4-cyclohexylmethylmorpholine, 1, 4-dioxane (99%) purchased from Tatan science; 3-Methyloxazolidines, benzoxazine (99%) were purchased from Jinjinle Chemicals; phosgene (not less than 95 percent) is prepared by a method provided by patent document CN 104415770A.