1. A method for preparing 2, 6-dichlorotoluene by chlorination of a chlorine-containing organic solvent in a subcritical state is characterized by comprising the following steps: adding a reactant 2-chloro-6-nitrotoluene into a chlorine-containing organic solvent, heating the chlorine-containing organic solvent in a closed container by using a gas with stable chemical properties as a filling gas, reacting for 1-24 h under the conditions of 200-: 100 mL to obtain a mixture, and finally separating and purifying to obtain the target product 2, 6-dichlorotoluene.

2. The method for preparing 2, 6-dichlorotoluene by subcritical chlorination of chlorine-containing organic solvent according to claim 1, wherein the chlorine-containing organic solvent is at least one of carbon tetrachloride, chloroform, trichloroethane, tetrachloroethane and sulfuryl chloride.

3. The method of claim 1, wherein the chemically stable gas is at least one of nitrogen, helium, neon, argon, krypton, xenon, and carbon dioxide.

4. The method for preparing 2, 6-dichlorotoluene through subcritical chlorination of chlorine-containing organic solvent according to claim 1, wherein the closed container is a stainless steel autoclave lined with polytetrafluoroethylene.

5. The method for preparing 2, 6-dichlorotoluene through subcritical chlorination of chlorine-containing organic solvent according to claim 1, wherein the separation process is heating stirring silica gel column chromatography or reduced pressure distillation.

6. The method for preparing 2, 6-dichlorotoluene by subcritical chlorination of chlorine-containing organic solvent according to claim 5, wherein the heated stirred silica gel column chromatography method comprises the following steps: heating the mixture in a fume hood by using a heating device of an oil bath method and a magnetic stirrer, keeping the temperature at 100-400 ℃, stirring the solution at the rotating speed of 100-1000 r/min, heating for 0.5-8 h, carrying out silica gel chromatography on the residue, using hexane as an eluent, activating the silica gel at 80-300 ℃, then loading dry silica gel into a column, adding the eluent for mixing, beating left and right to enable bubbles to rise and be discharged, carrying out pressurization operation, carrying out wet loading on the silica gel column, directly adding the liquid sample into the silica gel column, allowing the liquid to pass through the silica gel, enabling the silica gel to be adsorbed and stabilized, and then starting elution; and (4) using hexane as an eluent, and passing through a column at normal temperature and normal pressure to finally obtain the target product.

Background

2, 6-dichlorotoluene has the chemical formula C₇H₆Cl₂. 2, 6-dichlorotoluene is an important intermediate in industries such as dye, pesticide, medicine and the like, and can be used for synthesizing 2, 6-bis (dichlorotoluene)The compounds such as chlorobenzaldehyde, 2, 6-difluorobenzamide, 2, 6-difluorobenzonitrile, 2, 6-dichlorobenzonitrile, 2, 6-dichlorobenzoic acid, 2, 6-dichloroaniline, 2, 6-difluoroaniline and the like are basic raw materials of diclosoxacillin and can also be used for synthesizing a plurality of important medical products, such as 6-acetyl benzothiazole ketone.

There are many methods for synthesizing 2, 6-dichlorotoluene, such as: 3-chloro-2-methylaniline is used as a reactant, and is subjected to diazotization substitution and rectification to obtain 2, 6-dichlorotoluene; chlorinating p-tert-butyl toluene, removing tert-butyl, and finally rectifying to obtain 2, 6-dichlorotoluene; taking p-toluenesulfonic acid as a reactant, using sodium hypochlorite, sulfonyl chloride or concentrated hydrochloric acid to chlorinate with 30% hydrogen peroxide to obtain 3, 5-dichloro-4-toluenesulfonic acid, then removing sulfonic acid groups, and finally rectifying to obtain 2, 6-dichlorotoluene; taking p-methylbenzoic acid as a reactant, chlorinating, decarboxylating, and finally rectifying to obtain 2, 6-dichlorotoluene. In general terms: the existing synthesis method of 2, 6-dichlorotoluene has low yield and high manufacturing cost, or needs to use a catalyst and the like.

Disclosure of Invention

The technical problem to be solved is as follows: aiming at the problems in the prior art, the invention provides a method for preparing 2, 6-dichlorotoluene by chlorination of a chlorine-containing organic solvent in a subcritical state, and the method has the advantages of simple process, stable yield and the like.

The technical scheme is as follows: a method for preparing 2, 6-dichlorotoluene by chlorination of a chlorine-containing organic solvent under a subcritical state comprises the following steps: adding a reactant 2-chloro-6-nitrotoluene into a chlorine-containing organic solvent, heating the chlorine-containing organic solvent in a closed container by using a gas with stable chemical properties as a filling gas, reacting for 1-24 h under the conditions of 200-: 100 mL to obtain a mixture, and finally separating and purifying to obtain the target product 2, 6-dichlorotoluene.

Preferably, the chlorine-containing organic solvent is at least one of carbon tetrachloride, chloroform, trichloroethane, tetrachloroethane, and sulfuryl chloride.

Preferably, the chemically stable gas is at least one of nitrogen, helium, neon, argon, krypton, xenon, and carbon dioxide.

Preferably, the closed container is a stainless steel autoclave lined with polytetrafluoroethylene.

Preferably, the separation process is heating and stirring silica gel column chromatography or reduced pressure distillation.

Preferably, the method for the heated stirred silica gel column chromatography comprises the following steps: heating the mixture in a fume hood by using a heating device of an oil bath method and a magnetic stirrer, keeping the temperature at 100-400 ℃, stirring the solution at the rotating speed of 100-1000 r/min, heating for 0.5-8 h, carrying out silica gel chromatography on the residue, using hexane as an eluent, activating the silica gel at 80-300 ℃, then loading dry silica gel into a column, adding the eluent for mixing, beating left and right to enable bubbles to rise and be discharged, carrying out pressurization operation, carrying out wet loading on the silica gel column, directly adding the liquid sample into the silica gel column, allowing the liquid to pass through the silica gel, enabling the silica gel to be adsorbed and stabilized, and then starting elution; and (4) using hexane as an eluent, and passing through a column at normal temperature and normal pressure to finally obtain the target product.

The invention prepares 2, 6-dichlorotoluene by chlorination of 2-chloro-6-nitrotoluene, and chloric organic solvent is utilized to reach subcritical state under high temperature and high pressure condition, so that chlorine free radical generated by cracking C-Cl bond chlorinates 2-chloro-6-nitrotoluene, and 2, 6-dichlorotoluene is obtained.

The chemical reaction formula is as follows:

wherein the reaction condition is that a chlorine-containing organic solvent is added into a closed container, the chlorine-containing organic solvent is in a subcritical state at a certain temperature and under a certain pressure, an inactive gas is used as a filling gas, and the product is obtained after the system is reacted for a certain time. Subcritical fluids refer to substances in which certain compounds exist as fluids at temperatures above their boiling points but below their critical temperatures and at pressures below their critical pressures.

Has the advantages that: the method is simple and convenient, and the yield is stable. The chlorine with stronger toxicity needed by the existing research method is avoided, the safety of the synthetic method is improved, and the use and subsequent treatment of harmful substrates are reduced; on the other hand, the method does not need to additionally add a catalyst, is favorable for purifying and separating the product, and reduces the preparation cost.

Detailed Description

Specific embodiments of the present invention are further described below to provide those skilled in the art with a further understanding of the present invention, but are not to be construed as limiting the invention.

Example 1

The method for preparing 2, 6-dichlorotoluene by chlorination of 2-chloro-6-nitrotoluene comprises the following specific steps:

putting 2-chloro-6-nitrotoluene (4.0 mmol) into carbon tetrachloride (15 mL) in a fume hood, and fully stirring to completely dissolve the 2-chloro-6-nitrotoluene to obtain a mixture of the 2-chloro-6-nitrotoluene and the carbon tetrachloride;

putting the mixture into a 28 mL stainless steel autoclave lined with polytetrafluoroethylene, and introducing nitrogen as filling gas to ensure that the internal pressure of the reactor reaches 9 MPa;

heating a stainless steel autoclave lined with polytetrafluoroethylene at the constant temperature of 320 ℃ for 20 hours to fully react;

cooling the stainless steel autoclave lined with polytetrafluoroethylene to 20 ℃ by using clear water;

the components of the mixture are detected by a gas chromatograph, the temperature of a sample inlet is 260 ℃, the temperature of a column box is 160 ℃, and the conversion rate of the 2, 6-dichlorotoluene is 13.16 percent according to the correction factor.

Pouring the mixture into a beaker, heating in a fume hood by using an oil bath method and a heating device of a magnetic stirrer, keeping the temperature at 110 ℃, stirring the solution at the rotating speed of 600r/min, and heating for 1 h;

the residue was chromatographed on silica gel using hexane as eluent;

loading dried silica gel into column after silica gel is melted at 120 deg.C, adding eluent, mixing, beating left and right to make bubbles rise and discharge, and pressurizing;

carrying out wet loading on the silica gel column, directly adding a liquid sample into the silica gel column, allowing the liquid to pass through the silica gel, and starting elution after the silica gel is stably adsorbed; the mixture was passed through a column at ordinary temperature and pressure using hexane as an eluent to obtain 0.48mmol of 2, 6-dichlorotoluene.

Example 2

The method for preparing 2, 6-dichlorotoluene by chlorination of 2-chloro-6-nitrotoluene comprises the following specific steps:

in a fume hood, 2-chloro-6-nitrotoluene (4.0 mmol) is put into chloroform (15 mL) and fully stirred to completely dissolve the 2-chloro-6-nitrotoluene, so as to obtain a mixture of the 2-chloro-6-nitrotoluene and the chloroform;

putting the mixture into a 28 mL stainless steel autoclave lined with polytetrafluoroethylene, introducing helium gas serving as filling gas into the autoclave, and enabling the pressure inside the reactor to be accumulated to 8 MPa;

heating a stainless steel autoclave lined with polytetrafluoroethylene at a constant temperature of 270 ℃ for 7 hours to fully react;

cooling the stainless steel autoclave lined with polytetrafluoroethylene to 20 ℃ by using clear water;

the components of the mixture are detected by a gas chromatograph, the injection port temperature is 260 ℃, the column box temperature is 160 ℃, and the conversion rate of the 2, 6-dichlorotoluene obtained according to the correction factor is 71.35%.

The mixture was rectified under reduced pressure and the eluent was evaporated off by means of a vacuum pump and a rotary evaporator at a water temperature of 50 ℃ to give 2.82mmol of 2, 6-dichlorotoluene.

The existing research results show that the product yield is highest by using chloroform as a solvent and a chlorinating agent.

Example 3

The method for preparing 2, 6-dichlorotoluene by chlorination of 2-chloro-6-nitrotoluene comprises the following specific steps:

in a fume hood, 2-chloro-6-nitrotoluene (4.0 mmol) is put into trichloroethane (15 mL) and fully stirred to completely dissolve the 2-chloro-6-nitrotoluene, so as to obtain a mixture of the 2-chloro-6-nitrotoluene and the trichloroethane;

putting the mixture into a 28 mL stainless steel autoclave lined with polytetrafluoroethylene, introducing neon gas serving as filling gas into the autoclave to enable the pressure inside the reactor to be accumulated to 8MPa, and heating the autoclave at 250 ℃;

heating a stainless steel autoclave lined with polytetrafluoroethylene at a constant temperature of 250 ℃ for 7 hours to fully react;

cooling the stainless steel autoclave lined with polytetrafluoroethylene to 20 ℃ by using clear water;

the components of the mixture are detected by a gas chromatograph, the temperature of a sample inlet is 260 ℃, the temperature of a column box is 160 ℃, and the conversion rate of the 2, 6-dichlorotoluene obtained according to the correction factor is 68.33%.

Pouring the mixture into an evaporating dish, heating in a fume hood by using an oil bath method and a heating device of a magnetic stirrer, keeping the temperature at 110 ℃, stirring the solution at the rotating speed of 600r/min, and heating for 1 h;

the residue was chromatographed on silica gel using hexane as eluent;

activating silica gel at about 105 deg.C, loading dry silica gel into column, adding eluent, beating to make bubbles rise and discharge, and pressurizing;

the silica gel column was loaded and passed through the column at normal temperature and pressure using hexane as an eluent to give 2.69mmol of 2, 6-dichlorotoluene.

Example 4

The method for preparing 2, 6-dichlorotoluene by chlorination of 2-chloro-6-nitrotoluene comprises the following specific steps:

2-chloro-6-nitrotoluene (4.0 mmol) is put into tetrachloroethane (15 mL) in a fume hood and fully stirred to completely dissolve the 2-chloro-6-nitrotoluene, so as to obtain a mixture of the 2-chloro-6-nitrotoluene and the tetrachloroethane;

putting the mixture into a 28 mL stainless steel autoclave lined with polytetrafluoroethylene, and introducing nitrogen as filling gas to ensure that the pressure inside the reactor is accumulated to reach 7 MPa;

heating a stainless steel autoclave lined with polytetrafluoroethylene at a constant temperature of 310 ℃ for 13 hours to fully react;

cooling the stainless steel autoclave lined with polytetrafluoroethylene to 15 ℃ by using clear water;

the components of the mixture are detected by a gas chromatograph, the injection port temperature is 260 ℃, the column box temperature is 160 ℃, and the conversion rate of the 2, 6-dichlorotoluene obtained according to the correction factor is 12.77%.

Pouring the mixture into an evaporating dish, heating in a fume hood by using an oil bath method and a heating device of a magnetic stirrer, keeping the temperature at 110 ℃, stirring the solution at the rotating speed of 700r/min, and heating for 1 h;

the residue was chromatographed on silica gel using hexane as eluent;

activating silica gel at about 105 deg.C, loading dry silica gel into column, adding eluent, beating to make bubbles rise and discharge, and pressurizing;

the silica gel column was loaded and passed through the column at normal temperature and pressure using hexane as an eluent to give 2.93mmol of 2, 6-dichlorotoluene.