阅读说明：本技术 一种2,6-二羟基甲苯的合成方法 (Synthesis method of 2, 6-dihydroxytoluene ) 是由 舒恺 邹远林 华阳 黄友元 史丹丹 刘足和 方靖 刘郝敏 吴晓东 于 2021-09-01 设计创作，主要内容包括：本发明属于有机化学合成技术领域,具体涉及一种2,6-二羟基甲苯的合成方法；所述合成工艺包括以下步骤：S1：将2,6-二卤代甲苯,碱,重金属盐催化剂和吸附剂混合,加热水解得到2,6-二羟基甲苯的盐溶液；S2：将上述步骤得到的2,6-二羟基甲苯盐溶液用酸调节pH值至弱酸性,分离析出的固体,纯化得到2,6-二羟基甲苯的纯品；所使用的主要原料如2,6-二氯甲苯,氯化亚铜,十二烷基磺酸钠,氢氧化钾等均为市场上常见的化工原料,廉价易得,来源广泛；合成路线短,步骤少操作简便,节约了大量生产成本；反应条件温和,方便进行工业化生产；工艺路线三废较少,催化剂和吸附剂可以重复套用,进一步减少了三废的排放,对环境友好；全路线收率较高,有显著的成本优势。(The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a synthetic method of 2, 6-dihydroxytoluene; the synthesis process comprises the following steps: s1: mixing 2, 6-dihalogenotoluene, alkali, a heavy metal salt catalyst and an adsorbent, and heating and hydrolyzing to obtain a salt solution of 2, 6-dihydroxytoluene; s2: adjusting the pH value of the 2, 6-dihydroxytoluene salt solution obtained in the step to be weakly acidic by using acid, separating out precipitated solid, and purifying to obtain a pure product of the 2, 6-dihydroxytoluene; the main raw materials such as 2, 6-dichlorotoluene, cuprous chloride, sodium dodecyl sulfonate, potassium hydroxide and the like are common chemical raw materials in the market, are cheap and easily available, and have wide sources; the synthetic route is short, the steps are few, the operation is simple and convenient, and the mass production cost is saved; the reaction condition is mild, and the industrial production is convenient to carry out; the process route has less three wastes, the catalyst and the adsorbent can be repeatedly used, the discharge of the three wastes is further reduced, and the method is environment-friendly; the yield of the whole route is high, and the cost advantage is obvious.)

1. A method for synthesizing 2, 6-dihydroxytoluene is characterized in that: the synthesis process comprises the following steps:

s1: mixing 2, 6-dihalogenotoluene, alkali, a heavy metal salt catalyst and an adsorbent, and heating and hydrolyzing to obtain a salt solution of 2, 6-dihydroxytoluene;

s2: and (3) adjusting the pH value of the 2, 6-dihydroxytoluene salt solution obtained in the step to be weakly acidic by using acid, separating the separated solid, and purifying to obtain a pure product of the 2, 6-dihydroxytoluene.

Wherein the 2, 6-dihalotoluene isThe 2, 6-dihydroxytoluene salt isThe target product is

2. The method of claim 1, wherein the method comprises the steps of: the structural formula of the 2, 6-dihalotoluene in the step S1 isAnd the X and the Y are selected from one or two of chlorine, bromine and iodine.

3. The method of claim 1, wherein the method comprises the steps of: the alkali in step S1 is selected from one of solid or solution of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium hydride, sodium tert-butoxide and potassium tert-butoxide.

4. The method of claim 1, wherein the method comprises the steps of: the heavy metal salt in the step S1 is one of monovalent halides of copper, silver, gold and mercury, and the halogen is one of halogen chloride, bromine or iodine.

5. The method of claim 1, wherein the method comprises the steps of: the adsorbent in the step S1 is selected from one of sodium dodecyl sulfate, montmorillonite, diatomite and silica gel.

6. The method of claim 1, wherein the method comprises the steps of: the hydrolysis temperature in the step S1 is 60-140 ℃.

7. The method of claim 1, wherein the method comprises the steps of: the molar ratio of the 2, 6-dihalogenated toluene to the alkali to the catalyst to the adsorbent is 1: 3-5: 0.1:0.1: 3-5.

8. The method of claim 1, wherein the method comprises the steps of: the molar ratio of the 2, 6-dihalogenated toluene, the alkali, the catalyst and the adsorbent is 1:3:0.1:0.1: 3.

9. The method of claim 1, wherein the method comprises the steps of: the acid in step S2 is one of a sulfuric acid aqueous solution, a hydrochloric acid aqueous solution, a phosphoric acid aqueous solution, and an acetic acid aqueous solution.

10. The method of claim 1, wherein the method comprises the steps of: the pH value in the step S2 is 2-5.

Technical Field

The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a synthesis method of 2, 6-dihydroxytoluene.

Background

2, 6-dihydroxytoluene is an important chemical intermediate, and has wide application in the fields of synthetic resin, dyeing, medicines, pesticides, dyes, photosensitive materials and the like. In the field of medicine, the intermediate can be used as a raw material of short-thorn damnacanthus. In the field of pesticides, 2, 6-dihydroxytoluene can be used as an intermediate to synthesize a bipyrimidine salicylate herbicide. In the field of materials, 2, 6-dihydroxytoluene is used as a raw material to synthesize a series of porphyrin porphin compounds, and the compounds are widely applied to the aspects of high molecular materials and chemical catalysis.

Currently, the main synthesis methods of 2, 6-dihydroxytoluene include the following methods:

1. 3-chloro-2-methylaniline is used as a raw material, diazotization hydrolysis is carried out to obtain 3-chloro-2-methylphenol, and hydrolysis is carried out to obtain a target product. The diazotization reaction in the first step of the route has serious pollution and more three wastes. The second step reaction needs expensive rare earth catalyst and has high cost.

2. The second step is carried out under high temperature, high pressure and acidic conditions by using 2, 6-dinitrotoluene as a raw material, and has high requirements on equipment and harsh production conditions. If diazotisation is used, the contamination is serious and dangerous.

3. 1, 3-cyclohexanedione is used as a raw material and is finished by three steps of formaldehyde condensation, hydrogenation reduction and dehydrogenation. The steps are longer, more palladium carbon catalyst is needed to be consumed, and the cost is higher.

4. The target product is synthesized by using resorcinol as a raw material and methanol ammonium chloride at high temperature and high pressure. High requirements on equipment, more side reactions and unsuitability for large-scale industrial production.

Disclosure of Invention

The invention aims to: overcomes the defects in the prior art and provides a synthesis process of 2, 6-dihydroxytoluene with short synthesis route, less three wastes and low cost.

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

a synthetic method of 2, 6-dihydroxytoluene comprises the following steps:

s1: mixing 2, 6-dihalogenotoluene, alkali, a heavy metal salt catalyst and an adsorbent, and heating and hydrolyzing to obtain a salt solution of 2, 6-dihydroxytoluene;

s2: and (3) adjusting the pH value of the 2, 6-dihydroxytoluene salt solution obtained in the step to be weakly acidic by using acid, separating the separated solid, and purifying to obtain a pure product of the 2, 6-dihydroxytoluene.

Wherein the 2, 6-dihalotoluene isThe 2, 6-dihydroxytoluene salt isThe target product is

Further, the structural formula of the 2, 6-dihalotoluene in the step S1 isThe X and the Y are selected from one or two of chlorine, bromine and iodine, and are preferably 2, 6-dichlorotoluene.

Further, the base in step S1 is selected from one of solid or solution of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium hydride, sodium tert-butoxide, and potassium tert-butoxide, and preferably potassium hydroxide.

Further, the heavy metal salt in step S1 is one of monovalent halides of copper, silver, gold and mercury, and the halogen is one of halogen chloride, bromine and iodine, preferably cuprous chloride.

Further, the adsorbent in step S1 is selected from one of sodium dodecyl sulfate, montmorillonite, diatomaceous earth and silica gel, and is preferably sodium dodecyl sulfate.

Further, the hydrolysis temperature in the step S1 is 60-140 ℃.

Furthermore, the molar ratio of the 2, 6-dihalogenated toluene, alkali, catalyst and adsorbent is 1: 3-5: 0.1:0.1: 3-5.

Further, the molar ratio of the 2, 6-dihalotoluene, the alkali, the catalyst and the adsorbent is 1:3:0.1:0.1: 3.

Further, the acid in step S2 is one of an aqueous solution of sulfuric acid, an aqueous solution of hydrochloric acid, an aqueous solution of phosphoric acid, and an aqueous solution of acetic acid, and preferably an aqueous solution of hydrochloric acid.

Further, the pH value in step S2 is 2 to 5, preferably 3 to 4.

The technical scheme adopted by the invention has the beneficial effects that:

compared with other reported synthetic routes, the invention has the following advantages

1. The main raw materials such as 2, 6-dichlorotoluene, cuprous chloride, sodium dodecyl sulfonate, potassium hydroxide and the like are common chemical raw materials in the market, are cheap and easily available, and have wide sources.

2. The synthetic route is short, the steps are few, the operation is simple and convenient, and the mass production cost is saved.

3. The reaction condition is mild, and the industrial production is convenient to carry out.

4. The process route has less three wastes, the catalyst and the adsorbent can be repeatedly used, the discharge of the three wastes is further reduced, and the method is environment-friendly.

5. The yield of the whole route is high, and the cost advantage is obvious.

Detailed Description

The following will clearly and completely describe the technical solutions in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

The synthetic method of 2, 6-dihydroxytoluene comprises the following steps:

wherein, X and Y are one of chlorine, bromine and iodine, which can be the same or different; a is one of alkali metals such as potassium, sodium, lithium and the like. The heavy metal salt is 1-valent halogen salt of copper, silver, gold or mercury, such as cuprous chloride, cuprous iodide, silver chloride, etc. The adsorbent is sodium dodecyl sulfate, diatomite, montmorillonite, silica gel, etc.

The specific operation steps are as follows:

example 1

A1L autoclave was charged with 161 g of 2, 6-dichlorotoluene, 120g of sodium hydroxide, 5g of cuprous chloride, 1.6g of sodium dodecylsulfate and 480g of water. The reaction was heated to 120 ℃ for 8 hours with stirring closed and monitored by TLC until complete conversion of the starting material (the developing solvent was petroleum ether: ethyl acetate: 10: 1). Cooling to 40-50 ℃, and carrying out suction filtration. And (3) putting the filter cake into an oven for drying at the temperature of 80-100 ℃ to constant weight, and using the filter cake as a catalyst for feeding in the next batch.

Adjusting the pH value of the filtrate, namely the 2, 6-dihydroxy toluene sodium salt aqueous solution, to be 3-4 by using concentrated hydrochloric acid, stirring for 2 hours at 0-10 ℃, and performing suction filtration. Yellow solid is obtained, and the white crystal, namely 87 g of finished 2, 6-dihydroxytoluene product, is obtained by steam distillation and purification, the HPLC purity is more than 99 percent, and the yield is 75 percent.

Example 2

A1L autoclave was charged with 161 g of 2, 6-dichlorotoluene, 168g of potassium hydroxide, 5g of cuprous chloride, 3g of diatomaceous earth, and 480g of water. The reaction was heated to 100 ℃ for 6 hours with stirring closed and monitored by TLC until complete conversion of the starting material (the developing solvent was petroleum ether: ethyl acetate: 10: 1). Cooling to 40-50 ℃, and carrying out suction filtration. And drying the filter cake, and mechanically using the filter cake as a catalyst for feeding of the next batch.

Adjusting the pH value of the filtrate, namely the 2, 6-dihydroxytoluene sylvite aqueous solution, to be 3-4 by using concentrated hydrochloric acid, stirring for 2 hours at the temperature of 0-10 ℃, and performing suction filtration. Yellow solid is obtained, and 93 g of 2, 6-dihydroxytoluene finished product is obtained by steam distillation and purification, the HPLC purity is more than 99 percent, and the yield is 75 percent.

Example 3

250 g of 2, 6-dibromotoluene, 200g of sodium hydroxide, 10g of cuprous bromide, 5g of montmorillonite and 700g of water are put into a 2L autoclave. The reaction was heated to 140 ℃ for 7 hours with stirring closed and monitored by TLC until complete conversion of the starting material (the developing solvent was petroleum ether: ethyl acetate: 10: 1). Cooling to 40-50 ℃, and carrying out suction filtration. And drying the filter cake, and mechanically using the filter cake as a catalyst for feeding of the next batch.

Adjusting the pH value of the filtrate, namely 2, 6-dihydroxytoluene sodium salt aqueous solution, to 3-4 by using concentrated hydrochloric acid, stirring for 2 hours at 0-10 ℃, performing suction filtration to obtain a 2, 6-dihydroxytoluene crude product, recrystallizing toluene to obtain a finished product of 74g, wherein the HPLC purity is more than 99%, and the yield is 60%.

Example 4

Into a 2L autoclave were charged 320g of 2, 6-dichlorotoluene, 320g of sodium hydroxide, 20g of cuprous chloride, 20g of diatomaceous earth, and 1000g of water. The reaction was heated to 100 ℃ for 5 hours with stirring closed and monitored by TLC until complete conversion of the starting material (the developing solvent was petroleum ether: ethyl acetate: 10: 1). Cooling to 40-50 ℃, and carrying out suction filtration. And drying the filter cake, and mechanically using the filter cake as a catalyst for feeding of the next batch.

Adjusting the pH value of the filtrate, namely 2, 6-dihydroxytoluene sodium salt aqueous solution, to 3-4 by using concentrated hydrochloric acid, stirring for 2 hours at 0-10 ℃, performing suction filtration to obtain a crude product of 2, 6-dihydroxytoluene, and performing steam distillation to obtain 166g of a finished product of 2, 6-dihydroxytoluene, wherein the HPLC purity is more than 99%, and the yield is 67%.

It should be noted that: the autoclave is used in the present invention because the pressure may be high in the reaction process, and the pressure may be about 1MPa at 150 ℃ and about 0.5MPa at 120 ℃ and therefore, the autoclave is preferred for the closed heating reaction for safety.

Although the present invention has been described with reference to a preferred embodiment, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.