阅读说明：本技术 一种气固相法高效合成1r,2r-环己烷二甲醇的方法 (Method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by gas-solid phase method ) 是由 李福伟 高广 赵泽伦 孙鹏 龙向东 石利军 岳成涛 聂超 于 2019-10-23 设计创作，主要内容包括：本发明公开了一种气固相法高效合成1R,2R-环己烷二甲醇的方法。所述方法包括：在还原性气氛中,将1R,2R-环己烷二甲酸和/或1R,2R-环己烷二甲酸衍生物溶液连续输入设置有催化剂的连续管式反应器中,于空速0.01-1000g/g·h的条件下连续反应,获得1R,2R-环己烷二甲醇。本发明充分利用气固相法的特点,原料和产物只在反应体系中短暂停留,有效的阻止了手性化合物在高温下消旋化的发生,实现了1R,2R-环己烷二甲醇的连续化生产,适用于进行工业化生产。(The invention discloses a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method. The method comprises the following steps: in a reducing atmosphere, continuously inputting the 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivative solution into a continuous tubular reactor provided with a catalyst, and continuously reacting at a space velocity of 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol. The invention fully utilizes the characteristics of the gas-solid phase method, the raw materials and the products only temporarily stay in the reaction system, effectively prevents the chiral compound from deswirling at high temperature, realizes the continuous production of 1R, 2R-cyclohexanedimethanol, and is suitable for industrial production.)

1. A method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method is characterized by comprising the following steps:

continuously feeding the 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivative solution into a continuous tubular reactor provided with a catalyst in a reducing atmosphere, and continuously reacting at a space velocity of 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol.

2. The method of claim 1, comprising:

in a reducing atmosphere, continuously inputting 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivatives dissolved in a solvent into a continuous tubular reactor provided with a catalyst, and continuously reacting under the conditions that the pressure is 0.1-30MPa, the temperature is 20-300 ℃, and the space velocity is 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol.

3. The method according to claim 1, wherein the 1R, 2R-cyclohexanedicarboxylic acid derivative comprises any one or a combination of two or more of methyl 1R, 2R-cyclohexanedicarboxylate, ethyl 1R, 2R-cyclohexanedicarboxylate, propyl 1R, 2R-cyclohexanedicarboxylate and butyl 1R, 2R-cyclohexanedicarboxylate.

4. The method of claim 1, wherein the catalyst comprises an oxide support, and a catalytically active component supported on the oxide support, wherein the catalytically active component comprises a co-catalytic element, a hydrogenation metal element, and a precipitant.

5. The method according to claim 4, wherein the oxide support comprises any one or a combination of two or more of silica, molecular sieve, cobalt oxide, iron oxide, titanium oxide, magnesium oxide, and niobium oxide;

and/or the synergistic catalytic element comprises any one or the combination of more than two of rhenium, molybdenum, tin, tungsten and vanadium elements;

and/or the hydrogenation metal comprises any one or the combination of more than two of cobalt, ruthenium, nickel, platinum, copper, iridium and silver;

and/or the precipitant comprises any one or the combination of more than two of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia water, urea and ammonium carbonate.

6. The method according to claim 4, wherein the content of the synergistic catalytic element in the catalyst is 0.01-50 wt%;

and/or the content of hydrogenation metal in the catalyst is 0.01 wt% -50 wt%.

7. The method of claim 1, wherein the catalyst is prepared by a method comprising:

dipping an oxide carrier in a solution containing a synergistic catalytic element, drying, calcining the dried substance in air at 200-1200 ℃ for 5-24h, dipping the calcined substance in a solution containing a hydrogenation metal element, drying to obtain a catalyst precursor, calcining the catalyst precursor in air at 200-1200 ℃ for 5-24h, and finally reducing in a reducing atmosphere at 100-1000 ℃ for 1-24h to obtain the catalyst;

or dipping the oxide carrier into a mixed solution containing a synergistic catalytic element and a hydrogenation metal element, drying to obtain a catalyst precursor, calcining the catalyst precursor in air at 200-1200 ℃ for 5-24h, and carrying out reduction reaction at 100-1000 ℃ in a reducing atmosphere for 1-24h to obtain the catalyst;

or, the oxide carrier is evenly mixed in a solution containing the synergistic catalytic element and the hydrogenation metal element, then an alkaline solution is added, the mixture is stirred for 0.5 to 24 hours, then the temperature is raised to 0 to 100 ℃, the aging is carried out for 0.5 to 48 hours, then the obtained solid is calcined for 0.5 to 24 hours at 200-1200 ℃ in the air, and then the solid is reduced for 0.5 to 24 hours at 100-1000 ℃ in a reducing atmosphere, thus obtaining the catalyst.

8. The method according to claim 7, wherein the alkaline substance in the alkaline solution comprises any one or a combination of two or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and ammonia water.

9. The method of any one of claims 1, 2 or 7, wherein the reducing atmosphere is formed from a reducing gas;

preferably, the reducing gas includes hydrogen and/or a mixed gas containing hydrogen.

10. The method according to claim 2, wherein the solvent comprises any one or a combination of two or more of water, an alcohol solvent, an ether solvent, and a hydrocarbon solvent;

preferably, the alcohol solvent comprises any one or a combination of more than two of methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol and glycerol;

preferably, the ether solvent comprises one or more of tetrahydrofuran, diethyl ether, 1, 4-dioxane, diphenyl ether and tert-butyl methyl ether;

preferably, the hydrocarbon solvent includes any one or a combination of two or more of pentane, hexane, benzene, toluene, petroleum ether, dichloromethane and chloroform.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method.

Background

Alcohols containing chiral groups are a typical high value-added fine chemical, and particularly have very wide application in medical synthesis. 1R, 2R-cyclohexanedimethanol is an important intermediate in the synthesis of lurasidone hydrochloride (antipsychotic, sold annually at approximately 20 billion dollars, where the price of chiral diol monomer is approximately 400 million RMB/ton). The main processes for preparing chiral alcohols, including the above chiral diols, are: acid acylation-esterification-chemical reduction. The use of environmentally unfriendly acid chloride reagents and excess NaBH is required₄Reducing agent, generating a large amount of inorganic waste salt and waste water, and having long process route and high cost.

With H₂In order to clean a hydrogen source, the chiral alcohol compound prepared by heterogeneous catalytic hydrogenation of chiral carboxylic acid has the advantages of high synthesis efficiency, short route, low cost, easy obtainment of raw materials and the like, is close to ideal zero-pollution emission, and meets the technical requirements of the state for establishing a green ecological society. But is subject to the fact that chiral compounds easily occur in a high-temperature environment for a long timeRacemization, so the heterogeneous catalytic hydrogenation technology of chiral carboxylic acid is very deficient. The preparation method of the chiral cyclohexane dimethanol compound provided in patent CN 201810709488.3 is only carried out in a kettle type reaction, compared with a kettle type reaction gas-solid phase method, the method can avoid the retention of raw materials and products in a reaction system for a long time, and compared with the kettle type reaction, the gas-solid phase method is more beneficial to industrial continuous production, more importantly, the gas-solid phase method can avoid the long-time high-temperature environment of the raw materials and timely separate the products, which is very important for the chiral maintenance of the chiral compound, can effectively avoid the racemization of the chiral compound in the high-temperature environment for a long time, and provides guarantee for the chiral maintenance of the products. At present, the catalytic technology which can realize the high-efficiency synthesis of 1R, 2R-cyclohexanedimethanol at home and abroad is very deficient, so the key technology for developing the heterogeneous catalytic hydrogenation preparation and green new process of chiral alcohol compounds has very important economic and social significance.

Disclosure of Invention

The invention mainly aims to provide a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol, so as to overcome the defects in the prior art.

In order to achieve the purpose, the technical scheme adopted by the invention comprises the following steps:

the embodiment of the invention provides a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method, which comprises the following steps:

in a reducing atmosphere, continuously inputting the 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivative solution into a continuous tubular reactor provided with a catalyst, and continuously reacting at a space velocity of 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol.

Further, the method comprises: in a reducing atmosphere, continuously pumping 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivatives dissolved in a solvent into a continuous tubular reactor provided with a catalyst, and continuously reacting under the conditions that the pressure is 0.1-30MPa, the temperature is 20-300 ℃, and the space velocity is 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol.

Compared with the prior art, the invention provides a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method, which takes 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivatives as raw materials, and in the method for synthesizing 1R, 2R-cyclohexanedimethanol, the raw materials and the products only temporarily stay in a reaction system by changing a catalyst and fully utilizing the characteristics of the gas-solid phase method, so that the deswirl of a chiral compound at high temperature is effectively prevented, the continuous production of 1R, 2R-cyclohexanedimethanol is realized, and the method is suitable for industrial production.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments described in the present application, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 shows Pt-Re/TiO in example 8 of the present invention₂A transmission electron microscope image;

FIG. 2 is a graph showing the results of the service life of the catalyst in example 14 of the present invention.

Detailed Description

In view of the defects of the prior art, the present inventors have long studied and extensively practiced to propose the technical solution of the present invention, and further explain the technical solution, the implementation process and the principle, etc. as follows.

One aspect of the embodiments of the present invention provides a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol by a gas-solid phase method, comprising:

in a reducing atmosphere, continuously inputting the 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivative solution into a continuous tubular reactor provided with a catalyst, and continuously reacting at a space velocity of 0.01-1000 g/g.h to obtain the 1R, 2R-cyclohexanedimethanol.

In some embodiments, the method for the high efficiency synthesis of 1R, 2R-cyclohexanedimethanol comprises:

in a reducing atmosphere, continuously pumping 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivatives dissolved in a solvent into a continuous tubular reactor filled with a catalyst, and continuously reacting under the conditions of pressure of 0.1-30MPa, temperature of 20-300 ℃ and space velocity of 0.01-1000 g/g.h to obtain 1R, 2R-cyclohexanedimethanol, wherein the chemical reaction formula is shown as a formula (1).

In some embodiments, the catalyst comprises an oxide support, and a catalytically active component supported on the oxide support, wherein the catalytically active component comprises a co-catalytic element, a hydrogenation metal element, and a precipitant.

Further, the oxide support includes any one or a combination of two or more of silica, molecular sieve, cobalt oxide, iron oxide, titanium oxide, magnesium oxide, and niobium oxide, and is not limited thereto.

Further, the co-catalytic element includes any one or a combination of two or more of rhenium, molybdenum, tin, tungsten, vanadium elements, and is not limited thereto.

Further, the hydrogenation metal includes any one or a combination of two or more of cobalt, ruthenium, nickel, platinum, copper, iridium, and silver, and is not limited thereto.

Further, the precipitant includes any one or a combination of two or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia, urea, and ammonium carbonate, and is not limited thereto.

Furthermore, the content of the synergistic catalytic element in the catalyst is 0.01 wt% -50 wt%.

Furthermore, the content of the hydrogenation metal in the catalyst is 0.01 wt% -50 wt%.

In some embodiments, the method of preparing the catalyst comprises:

dipping an oxide carrier in a solution containing a synergistic catalytic element, drying, calcining the dried substance in air at 200-1200 ℃ for 5-24h, dipping the calcined substance in a solution containing a hydrogenation metal element, drying to obtain a catalyst precursor, calcining the catalyst precursor in air at 200-1200 ℃ for 5-24h, and finally reducing in a reducing atmosphere at 100-1000 ℃ for 1-24h to obtain the catalyst;

or dipping the oxide carrier into a mixed solution containing a synergistic catalytic element and a hydrogenation metal element, drying to obtain a catalyst precursor, calcining the catalyst precursor in air at 200-1200 ℃ for 5-24h, and carrying out reduction reaction at 100-1000 ℃ in a reducing atmosphere for 1-24h to obtain the catalyst;

or, the oxide carrier is evenly mixed in a solution containing the synergistic catalytic element and the hydrogenation metal element, then an alkaline solution is added, the mixture is stirred for 0.5 to 24 hours, then the temperature is raised to 0 to 100 ℃, the aging is carried out for 0.5 to 48 hours, then the obtained solid is calcined for 0.5 to 24 hours at 200-1200 ℃ in the air, and then the solid is reduced for 0.5 to 24 hours at 100-1000 ℃ in a reducing atmosphere, thus obtaining the catalyst.

In some more specific embodiments, the method of making can comprise:

fully soaking the carrier in a solution containing the synergistic catalytic element, evaporating the solution, drying, and calcining in air at 200-1200 ℃ for 1-24 h; and then fully soaking the obtained material in a solution containing a hydrogenation metal element, evaporating the solution, drying, calcining for 1-24h at 200-1200 ℃ in air, and reducing for 0.5-24h at 100-1000 ℃ in a reducing atmosphere, or directly reducing for 0.5-24h at 100-1000 ℃ in a reducing atmosphere without calcining in air to form the catalyst.

In some more specific embodiments, the preparation method may further comprise:

the carrier is fully and uniformly stirred in a solution containing a synergistic catalytic element and a hydrogenation metal element, an alkaline solution with a certain concentration is slowly dripped, the stirring is continued for 0.5 to 24 hours, the temperature is increased to 0 to 100 ℃, the aging is carried out for 0.5 to 48 hours, the filtration, the water washing and the drying are carried out, then the calcination is carried out for 1 to 24 hours in the air at 200-1200 ℃, and the reduction is carried out for 0.5 to 24 hours in the reducing atmosphere at 100-1000 ℃, or the reduction is directly carried out for 0.5 to 24 hours in the reducing atmosphere at 100-1000 ℃ without the calcination in the air, thus forming the catalyst.

In some more specific embodiments, the preparation method may further comprise:

fully soaking the carrier in a solution containing the synergistic catalytic element and the hydrogenation metal element, evaporating the solution, drying, calcining at the temperature of 200-1200 ℃ in air for 0.5-24h, and then reducing at the temperature of 1000 ℃ in a reducing atmosphere for 0.5-24h, or directly reducing at the temperature of 1000 ℃ in the reducing atmosphere for 0.5-24h without calcining in air to form the catalyst.

Further, the alkaline substance in the alkaline solution includes any one or a combination of two or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and ammonia water, and is not limited thereto.

In some embodiments, the 1R, 2R-cyclohexanedicarboxylic acid derivative comprises any one or a combination of two or more of methyl 1R, 2R-cyclohexanedicarboxylate, ethyl 1R, 2R-cyclohexanedicarboxylate, propyl 1R, 2R-cyclohexanedicarboxylate, and butyl 1R, 2R-cyclohexanedicarboxylate, without being limited thereto.

Further, the reducing atmosphere is formed of a reducing gas.

Further, the reducing gas includes hydrogen and/or a mixed gas containing hydrogen.

In some embodiments, the solvent includes any one or a combination of two or more of water, an alcohol solvent, an ether solvent, and a hydrocarbon solvent, and is not limited thereto.

Further, the alcohol solvent includes any one or a combination of two or more of methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert-butanol, ethylene glycol, and glycerol, and is not limited thereto.

Further, the ether solvent includes any one or a combination of two or more of tetrahydrofuran, diethyl ether, 1, 4-dioxane, diphenyl ether, and t-butyl methyl ether, and is not limited thereto.

Further, the hydrocarbon solvent includes any one or a combination of two or more of pentane, hexane, benzene, toluene, petroleum ether, dichloromethane, and chloroform, and is not limited thereto.

By the technical scheme, the invention provides a method for efficiently synthesizing 1R, 2R-cyclohexanedimethanol, which takes 1R, 2R-cyclohexanedicarboxylic acid and/or 1R, 2R-cyclohexanedicarboxylic acid derivatives as raw materials, and in the method for synthesizing 1R, 2R-cyclohexanedimethanol, through changing catalysts and fully utilizing the characteristics of a gas-solid phase method, the raw materials and products only temporarily stay in a reaction system, so that the deswirl of a chiral compound at high temperature is effectively prevented, the continuous production of 1R, 2R-cyclohexanedimethanol is realized, and the method is suitable for industrial production.

The technical solution of the present invention is further described in detail with reference to several preferred embodiments, which are implemented on the premise of the technical solution of the present invention, and detailed embodiments and specific operation procedures are given, but the scope of the present invention is not limited to the following embodiments.