Preparation process of trans-4-methylcyclohexyl isocyanate

Abstract

The invention provides a preparation process of trans-4-methylcyclohexyl isocyanate. The preparation process comprises the following steps: S1, mixing trans-4-methylcyclohexyl amine, an organic solvent, an auxiliary agent and a stabilizer to obtain a homogeneous-phase mixed solution A; mixing and dispersing a cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and a 5molecular sieve in an organic solvent, and performing ultrasonic treatment to obtain a suspension B; s2, continuously introducing the mixed solution A, the suspension solution B and carbon dioxide into a microreactor system, and carrying out carbonylation reaction under the action of a cobalt-based porous organic cage bifunctional catalyst at the reaction temperature of 75-90 DEG C under the pressure of 0.4-0.6 MPa for 20-35 minutes; and S3, carrying out solid-liquid separation on the reaction liquid to recover the cobalt-based porous organic cage bifunctional catalyst, carrying out rectification on the supernatant to recover the organic solvent and triethyl orthoformate, and carrying out molecular distillation on the residue to obtain trans-4-methylcyclohexyl isocyanate. According to the invention, high conversion rate of raw materials and high yield of target products can be realized, and recycling of the catalyst, the organic solvent and triethyl orthoformate is realized.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis intermediates, specifically to a preparation process for trans-4-methylcyclohexyl isocyanate. Background Technology

[0002] Trans-4-methylcyclohexyl isocyanate is an important organic synthetic intermediate widely used in chemical pharmaceutical raw materials, formulation manufacturing, medicine, pesticides, polyurethane materials, and other fields. Optimizing its preparation process is of great significance to the development of related industries. Currently, the preparation of trans-4-methylcyclohexyl isocyanate mainly uses amino-containing precursors as raw materials, achieved through isocyanation reactions. Existing processes include various routes such as the phosgene method and the non-phosgene method.

[0003] In the non-phosgene process for preparing trans-4-methylcyclohexyl isocyanate, batch reaction modes are often employed, resulting in insufficient mass and heat transfer efficiency. This necessitates harsh conditions such as high temperature and pressure, affecting not only the stability and continuity of the reaction but also leading to incomplete conversion of raw materials and hindering further improvement in the yield of the target product. Furthermore, the catalysts used in the process are prone to deactivation or difficult to recover efficiently, and the recovery rate of auxiliary materials such as organic solvents is low. This increases material losses and production costs during the process and may also create environmental pressure due to waste emissions. Therefore, developing a preparation process that can achieve continuous and stable production under mild conditions, with high raw material conversion efficiency and efficient recovery of catalysts and auxiliary materials is a pressing technical problem to be solved in this field. Summary of the Invention

[0004] To address the problems existing in the prior art, the present invention provides a preparation process for trans-4-methylcyclohexyl isocyanate.

[0005] To achieve the above objectives, the present invention provides the following technical solution: This application discloses a process for preparing trans-4-methylcyclohexyl isocyanate, comprising the following steps: S1. Raw material preparation: A homogeneous mixture A is obtained by mixing trans-4-methylcyclohexylamine, organic solvent, auxiliaries and stabilizers; a suspension B is obtained by mixing and dispersing cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and 5Å molecular sieve in an organic solvent and ultrasonically treating it. S2, Continuous flow carbonylation reaction: Mixture A, suspension B and carbon dioxide are continuously fed into the microreactor system, and the carbonylation reaction is carried out under the action of cobalt-based porous organic cage bifunctional catalyst. The reaction temperature is 75-90℃, the pressure is 0.4-0.6MPa, and the residence time is 20-35min. S3. Product separation and purification: The reaction solution is separated by solid-liquid separation to recover the cobalt-based porous organic cage bifunctional catalyst. The supernatant is distilled to recover the organic solvent and triethyl orthoformate. The residue is molecularly distilled to obtain trans-4-methylcyclohexyl isocyanate.

[0006] Using the above technical solution, trans-4-methylcyclohexylamine is used as a raw material to provide amino sites for the reaction. A cobalt-based porous organic cage bifunctional catalyst can efficiently catalyze the carbonylation reaction. Triethyl orthoformate combines with the water generated in the reaction through chemical action, and a 5Å molecular sieve removes trace amounts of water from the system through physical adsorption. The synergistic dehydration of these two components can drive the carbonylation reaction equilibrium to the forward direction. Organic solvents ensure the dissolution and dispersion of all raw materials and intermediates, while additives and stabilizers help improve reaction stability. The homogeneous mixture A, suspension B, and carbon dioxide are continuously introduced into the microreactor system. The system conducts the carbonylation reaction. The microreactor system can enhance the mass and heat transfer efficiency. Under mild conditions of 75-90℃, 0.4-0.6MPa and a residence time of 20-35min, the reaction can be carried out continuously and stably. Subsequently, the cobalt-based porous organic cage bifunctional catalyst can be recovered through solid-liquid separation, and the organic solvent and triethyl orthoformate can be recovered through distillation. Then, trans-4-methylcyclohexyl isocyanate is obtained through molecular distillation. The overall process can achieve high conversion rate of raw materials and high yield of target products, while realizing the recovery and utilization of catalyst, organic solvent and triethyl orthoformate.

[0007] Preferably, the raw materials for preparing trans-4-methylcyclohexyl isocyanate, by weight, include: 95-105 parts of trans-4-methylcyclohexylamine, 8-15 parts of cobalt-based porous organic cage bifunctional catalyst, 20-35 parts of triethyl orthoformate, 5-10 parts of 5Å molecular sieve, 200-400 parts of organic solvent, 0.8-2.5 parts of additives, and 0.3-1.5 parts of stabilizer, wherein the molar ratio of carbon dioxide to trans-4-methylcyclohexylamine is (1.0-1.2):1.

[0008] Using the above technical solution, trans-4-methylcyclohexylamine serves as a raw material to provide amino sites for the reaction. A cobalt-based porous organic cage bifunctional catalyst catalyzes the carbonylation reaction of trans-4-methylcyclohexylamine with carbon dioxide. Triethyl orthoformate and 5Å molecular sieve work synergistically to dehydrate and promote the forward shift of the reaction equilibrium. Organic solvents ensure the dissolution and dispersion of each raw material and reaction intermediate. Additives help improve reaction efficiency, and stabilizers reduce side reactions to maintain the stability of the reaction system. Meanwhile, the reaction of carbon dioxide and trans-4-methylcyclohexylamine at a molar ratio of (1.0-1.2):1 ensures a sufficient supply of carbonylating reagent to promote the full reaction. The combined effect of all components enables the efficient preparation of trans-4-methylcyclohexyl isocyanate, and the reaction process is stable and controllable.

[0009] Preferably, the organic solvent is a mixture of dimethylacetamide, N-methylpyrrolidone, or dimethylacetamide and dimethyl carbonate in a volume ratio of (2.8-3.2):1.

[0010] Using the above technical solution, dimethylacetamide and N-methylpyrrolidone are both polar aprotic solvents, which have good solubility and dispersibility for reaction components such as trans-4-methylcyclohexylamine and cobalt-based porous organic cage bifunctional catalysts, thus ensuring the homogeneity of the reaction system and promoting the smooth progress of the reaction. The mixed system composed of dimethylacetamide and dimethyl carbonate can combine the characteristics of the two solvents, maintaining good solubility for each reaction component and adjusting the relevant properties of the system, further ensuring the stable progress of the reaction.

[0011] Preferably, the auxiliary agent is tris(pentafluorophenyl)borane or boron trifluoride diethyl ether complex; the stabilizer is triphenyl phosphite.

[0012] Using the above technical solution, both tri(pentafluorophenyl)borane and boron trifluoride diethyl ether complex can assist in activating carbon dioxide in the reaction system, promoting the carbonylation reaction of trans-4-methylcyclohexylamine with carbon dioxide; triphenyl phosphite can combine with trace by-products generated during the reaction and inhibit the polymerization reaction of isocyanate, while reducing the generation of oxidizing impurities, maintaining the stability of the reaction system and the purity of the product.

[0013] Preferably, the preparation method of the cobalt-based porous organic cage bifunctional catalyst includes the following steps: 1) Under nitrogen protection, trialdehyde phloroglucinol and (R,R)-1,2-diaminocyclohexane were ultrasonically dispersed and dissolved in 1,2-dichloroethane and acetic acid. After dissolution, the mixture was transferred to a reaction vessel under nitrogen protection and refluxed at 70-75°C for 36-48 h. After washing and drying, a chiral porous organic cage was obtained. 2) Disperse the chiral porous organic cage in anhydrous ethanol, add cobalt chloride hexahydrate and 4-dimethylaminopyridine, react at 60-65℃ for 20-24h, and obtain the cobalt-based porous organic cage intermediate by centrifugation, washing and drying. 3) The cobalt-based porous organic cage intermediate was ball-milled with silica gel trifluoromethanesulfonate, washed with ether, and then vacuum dried to obtain a cobalt-based porous organic cage bifunctional catalyst.

[0014] Using the above technical solution, nitrogen protection is used to avoid interference from impurities during the reaction process, ultrasonic dispersion and dissolution ensure uniform mixing of raw materials, and reflux reaction promotes the full reaction of trialdehyde-based phloroglucinol with (R,R)-1,2-diaminocyclohexane to generate a chiral porous organic cage. Subsequently, by introducing cobalt chloride hexahydrate and combining it with reaction and centrifugation, stable loading of cobalt-based active sites on the organic cage is achieved. Then, acidic sites of trifluoromethanesulfonic acid silica gel are introduced through ball milling, free acid is removed by ether washing, and vacuum drying ensures the purity and stability of the catalyst. The overall preparation process can obtain a bifunctional catalyst with cobalt-based porous organic cages that simultaneously possesses cobalt-based active sites and acidic sites. The rigid framework structure of the porous organic cage can endow the catalyst with a specific confined space structure, ensuring its selectivity and catalytic performance stability for substrates in subsequent reactions. The cobalt-based active sites are responsible for activating carbon dioxide molecules and lowering the activation energy barrier of the carbonylation reaction; the acidic sites can protonate reaction intermediates and promote the dehydration step. The synergistic effect of the two significantly improves the reaction efficiency and selectivity.

[0015] Preferably, in step 1), the amount of trialdehyde phloroglucinol used is 9.0-11.0 g, the amount of (R,R)-1,2-diaminocyclohexane used is 15.0-17.5 g, the amount of 1,2-dichloroethane used is 280-320 mL, and the amount of acetic acid used is 18-22 mL; the power of ultrasonic dispersion and dissolution is 140-160 W, and the ultrasonic time is 25-35 min; the washing process uses methanol to wash 2-4 times, with a single washing volume of 90-110 mL; the drying conditions are: temperature 75-85℃, vacuum degree -0.09~-0.11 MPa (gauge pressure), and time 10-14 h.

[0016] Using the above technical solution, it is possible to ensure that trialdehyde phloroglucinol and (R,R)-1,2-diaminocyclohexane are fully contacted in the 1,2-dichloroethane and acetic acid system. Ultrasonic dispersion and dissolution can achieve uniform mixing of raw materials to ensure reaction uniformity. Methanol washing can effectively remove reaction residues and impurities. Specific drying conditions can completely remove solvents and moisture from the solid, ultimately obtaining a chiral porous organic cage with qualified purity and stable structure, providing a suitable carrier for subsequent cobalt-based active site loading and acidic site introduction.

[0017] Preferably, in step 2), the amount of chiral porous organic cage is 5.0-7.0 g, the amount of cobalt chloride hexahydrate is 8.5-10.5 g, and the amount of 4-dimethylaminopyridine is 1.1-1.3 g; the centrifugation speed is 7500-8500 r / min, and the centrifugation time is 12-18 min; the washing process uses anhydrous ethanol to wash 2-4 times; the drying conditions are: temperature 55-65℃, vacuum degree -0.09~-0.11 MPa, and time 6-10 h.

[0018] By employing the above technical solution, sufficient contact and reaction between the chiral porous organic cage and cobalt chloride hexahydrate and 4-dimethylaminopyridine can be ensured, achieving effective loading of cobalt-based active sites on the organic cage. Centrifugation at specific speeds and times can efficiently separate the solid product from the reaction liquid. Washing with anhydrous ethanol can remove unreacted raw materials and impurities remaining on the solid surface. Targeted drying conditions can completely remove solvents and moisture from the solid, ultimately obtaining a cobalt-based porous organic cage intermediate with qualified purity and stable loading of cobalt-based active sites, providing a stable substrate for the subsequent introduction of acidic sites.

[0019] Preferably, in step 3), the loading of trifluoromethanesulfonic acid in the trifluoromethanesulfonic acid silica gel is 8wt%-10wt%, the mass ratio of cobalt-based porous organic cage intermediate to trifluoromethanesulfonic acid silica gel is (1.0-1.2):1, the ball milling speed is 280-320 r / min, and the ball milling time is 1.5-2.5 h; the vacuum drying conditions are: temperature 35-45℃, vacuum degree -0.09~-0.11 MPa, and time 5-7 h.

[0020] By adopting the above technical solution, it is possible to ensure that the cobalt-based porous organic cage intermediate and the trifluoromethanesulfonic acid silica gel are fully mixed. Specific ball milling speed and time can achieve uniform dispersion and effective binding of acidic sites on the intermediate. Targeted vacuum drying conditions can completely remove solvents and moisture from the solid, while avoiding damage to the structure of acidic sites and cobalt-based active sites caused by high temperature. Finally, a cobalt-based porous organic cage bifunctional catalyst with stable acidic site content and reliable performance is obtained, ensuring that it has both efficient carbon dioxide activation and intermediate dehydration capabilities in subsequent reactions.

[0021] Preferably, in step S1, the organic solvent used to prepare mixture A and the organic solvent used to prepare suspension B are from the same system, and the mass ratio of the two is (2.5-3.5):1. During the preparation of mixture A, the mixture is stirred at a speed of 150-200 r / min for 30-45 min. The ultrasonic treatment conditions for preparing suspension B are: ultrasonic power 190-210 W, treatment time 20-30 min.

[0022] By employing the above technical solution, mixture A and suspension B use the same organic solvent system, ensuring the compatibility and stability of the subsequent reaction system and avoiding uneven material dispersion or reaction interference caused by mixing different solvents. A specific mass ratio is adapted to the required proportions of the reactants, ensuring efficient reaction progress. The stirring parameters of mixture A achieve sufficient dissolution and uniform mixing of trans-4-methylcyclohexylamine, auxiliaries, and stabilizers, forming a homogeneous and transparent system. The ultrasonic conditions of suspension B promote the uniform dispersion of the cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate, and 5Å molecular sieve, preventing catalyst agglomeration that leads to insufficient exposure of active sites, while ensuring the full utilization of the dehydrated components, laying the foundation for efficient and stable continuous flow reactions.

[0023] Preferably, in step S2, the pumping rate of mixture A is 2-5 mL / min, and the pumping rate of suspension B is 0.8-1.5 mL / min; both mixture A and suspension B are preheated before being introduced into the microreactor system at a preheating temperature of 40-50℃; the main reactor employs three-stage temperature control: the first stage at 75-80℃, the middle stage at 80-85℃, and the last stage at 85-90℃; the characteristic peak of NCO (2270 cm⁻¹) is monitored online using infrared spectroscopy. -1 When the intensity of the NCO characteristic peak no longer changes significantly with time (i.e., the rate of change is ≤1% / min), the reaction is considered to have reached its endpoint. In step S3, solid-liquid separation is performed using a continuous centrifuge at a speed of 8000-10000 r / min; distillation recovery is carried out at 80-90℃ and a vacuum of -0.095~-0.098 MPa (gauge pressure); molecular distillation is performed in two stages: the first stage removes low-boiling substances at 100-110℃ and 10-20 Pa, and the second stage collects the main fraction at 125-135℃ and 1-3 Pa; the recovered cobalt-based porous organic cage bifunctional catalyst is washed 2-3 times with anhydrous ethanol, filtered, and dried at 75-85℃ and a vacuum of -0.09~-0.10 MPa (gauge pressure) for 6-8 h, and can be reused. After being reused 5 times, the relative initial catalytic activity retention rate is ≥88%; the cobalt residue in the product is ≤0.5 ppm.

[0024] Using the above technical solution, in step S2, the pumping speed of mixture A and suspension B matches the material ratio requirements to ensure sufficient contact between the reaction components; the preheating temperature ensures that the materials reach a suitable state before entering the main reactor, reducing the impact of temperature fluctuations on the reaction; the three-stage gradient heating matches the reaction process, gradually promoting the formation of intermediates and the complete dehydration reaction, improving conversion efficiency and selectivity; online infrared monitoring of the NCO characteristic peak can accurately determine the reaction endpoint, avoiding raw material residue or over-reaction. In step S3, high centrifugal speed can efficiently separate the catalyst and 5Å molecular sieve, avoiding impurities from interfering with subsequent purification; the temperature and vacuum conditions of distillation recovery can ensure the effective recovery of solvent and triethyl orthoformate while preventing product decomposition; the two-stage molecular distillation process respectively achieves the removal of low-boiling substances and the precise collection of the main fraction, improving product purity; the washing and drying conditions of the catalyst can effectively remove residual impurities, thoroughly remove water, protect active sites, ensure stable activity for repeated use, and control the cobalt residue in the product to meet the quality requirements of pharmaceutical intermediates.

[0025] The beneficial effects of this invention are as follows: trans-4-methylcyclohexylamine provides amino sites as a reactant. A cobalt-based porous organic cage bifunctional catalyst catalyzes the carbonylation reaction efficiently. Triethyl orthoformate combines with the water generated in the reaction through chemical action, while a 5Å molecular sieve removes trace amounts of water from the system through physical adsorption. The synergistic dehydration by these two catalysts promotes the forward shift of the carbonylation reaction equilibrium. Organic solvents ensure the dissolution and dispersion of all raw materials and intermediates, while auxiliaries and stabilizers help improve reaction stability. Homogeneous mixture A, suspension B, and carbon dioxide are continuously introduced into the microreactor system for carbonylation. The microreactor system enhances mass and heat transfer efficiency, enabling continuous and stable reaction under mild conditions of 75-90℃, 0.4-0.6MPa, and a residence time of 20-35min. Subsequent solid-liquid separation allows for the recovery of the cobalt-based porous organic cage bifunctional catalyst, while distillation recovers the organic solvent and triethyl orthoformate. Molecular distillation then yields trans-4-methylcyclohexyl isocyanate. The overall process achieves high conversion rates of raw materials and high yields of target products, while simultaneously enabling the recovery and utilization of catalysts, organic solvents, and triethyl orthoformate.

[0026] Trans-4-methylcyclohexylamine serves as a raw material, providing amino sites for the reaction. A cobalt-based porous organic cage bifunctional catalyst catalyzes the carbonylation reaction of trans-4-methylcyclohexylamine with carbon dioxide. Triethyl orthoformate and 5Å molecular sieve work synergistically to dehydrate the reaction and promote the forward shift of the reaction equilibrium. Organic solvents ensure the dissolution and dispersion of raw materials and reaction intermediates. Additives help improve reaction efficiency, and stabilizers reduce side reactions to maintain the stability of the reaction system. Meanwhile, the reaction of carbon dioxide and trans-4-methylcyclohexylamine at a molar ratio of (1.0-1.2):1 ensures a sufficient supply of carbonylating reagent to promote the full reaction. The combined effect of all components enables the efficient preparation of trans-4-methylcyclohexyl isocyanate, and the reaction process is stable and controllable. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the three-dimensional structural model of the cobalt-based porous organic cage bifunctional catalyst in this invention; Gray network: Represents the skeletal structure of porous organic cage (POC) (providing high specific surface area and confined space); The marked "cobalt active site" and "acidic site" correspond to the bifunctional active centers of the catalyst (responsible for activating CO2 and promoting dehydration, respectively). "Porous channels": Show the pore distribution of the carrier (ensuring mass transfer efficiency of reactants / products). Detailed Implementation

[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Specific information on the raw materials used in the embodiments of this invention is shown in Table 1: Table 1. Raw material names and sources

[0030] Example 1: This embodiment discloses a preparation process for trans-4-methylcyclohexyl isocyanate. The raw materials for preparing trans-4-methylcyclohexyl isocyanate include, by weight, 95g of trans-4-methylcyclohexylamine, 8g of cobalt-based porous organic cage bifunctional catalyst, 20g of triethyl orthoformate, 5g of 5Å molecular sieve, 200g of organic solvent, 0.8g of tri(pentafluorophenyl)borane, and 0.3g of triphenyl phosphite. The organic solvent is dimethylacetamide.

[0031] The preparation process of trans-4-methylcyclohexyl isocyanate includes the following steps: S1. Raw material preparation: Take trans-4-methylcyclohexylamine, organic solvent, tris(pentafluorophenyl)borane and triphenyl phosphite, and stir at 150 r / min for 30 min to obtain homogeneous mixture A; Cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and 5Å molecular sieve were mixed and dispersed in an organic solvent and ultrasonically treated at an ultrasonic power of 190W for 20 min to obtain a uniform suspension B. The organic solvent used to prepare mixture A and the organic solvent used to prepare suspension B are from the same system, and their mass ratio is 2.5:1. S2, Continuous flow carbonylation reaction: The microreactor system was purged with high-purity nitrogen for 25 minutes to remove air and moisture from the system, and then the mixture A and suspension B were preheated to 40°C. Preheated mixture A was pumped into the microreactor system at a flow rate of 2 mL / min, and preheated suspension B was pumped into the microreactor system at a flow rate of 0.8 mL / min. A mass flow controller was used to control the feeding of carbon dioxide at a stoichiometric rate of 1.0 equivalent (molar ratio of carbon dioxide to trans-4-methylcyclohexylamine was 1.0:1). The carbonylation reaction was carried out under the action of a cobalt-based porous organic cage bifunctional catalyst. The pressure was controlled at 0.4 MPa, the residence time at 20 min, and the reaction temperature was controlled in three stages: 75℃ in the first stage, 80℃ in the middle stage, and 85℃ in the final stage. The characteristic peak of NCO (2270 cm⁻¹) was monitored by online infrared spectroscopy. -1 When the intensity of the NCO characteristic peak no longer changes significantly with time (i.e., the rate of change is ≤1% / min), the reaction is considered to have reached its endpoint. S3. Product separation and purification: After the reaction solution was cooled to 25°C, it was then centrifuged at 8000 r / min for 15 min to separate the cobalt-based porous organic cage bifunctional catalyst and the 5 Å molecular sieve. The recovered cobalt-based porous organic cage bifunctional catalyst was washed twice with anhydrous ethanol, filtered, and dried at 75°C and a vacuum of -0.09 MPa (gauge pressure) for 6 h. It can be reused. After being reused 5 times, the relative initial catalytic activity retention rate is ≥88%; the cobalt residue in the product is ≤0.5 ppm (detected by inductively coupled plasma mass spectrometry (ICP-MS)). The supernatant enters a falling film evaporator and is subjected to distillation at 80°C and a vacuum of -0.095 MPa (gauge pressure) to recover the organic solvent and triethyl orthoformate. The residue is then distilled in a short-path molecular distillation apparatus under the following conditions: First stage: Removal of low-boiling-point substances at 100℃ and 10Pa; Second stage: 125℃, 1Pa, collect the main fraction (trans-4-methylcyclohexyl isocyanate).

[0032] The preparation method of cobalt-based porous organic cage bifunctional catalyst includes the following steps: 1) Synthesis of porous organic cage framework: Under nitrogen protection, 9g of trialdehyde phloroglucinol and 15g of (R,R)-1,2-diaminocyclohexane were ultrasonically dispersed and dissolved in 280mL of 1,2-dichloroethane and 18mL of acetic acid. The ultrasonic power was 140W and the ultrasonic time was 25min. After dissolution, the mixture was transferred to a reaction vessel under nitrogen protection and refluxed at 70°C for 36 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered to collect the solid, washed twice with methanol (90 mL each time), and then dried at 75 °C and a vacuum of -0.09 MPa (gauge pressure) for 10 h to obtain a chiral porous organic cage. 2) Cobalt-based active site loading: 5g of chiral porous organic cage was dispersed in 180mL of anhydrous ethanol and stirred at 150r / min for 25min under nitrogen protection. Add 8.5g of cobalt chloride hexahydrate and 1.1g of 4-dimethylaminopyridine, react at 60℃ for 20h, centrifuge at 7500r / min for 12min, wash the solid twice with anhydrous ethanol, and then dry at 55℃ and vacuum degree -0.09MPa for 6h to obtain cobalt-based porous organic cage intermediate. 3) Introduction of acidic sites: The cobalt-based porous organic cage intermediate was mixed with trifluoromethanesulfonic acid silica gel with a loading of 8 wt% at a mass ratio of 1.0:1, and then added to an agate ball mill jar. The mixture was ball milled at 280 r / min for 1.5 h. Add 45 mL of anhydrous diethyl ether, stir for 8 min, filter to remove free acid, and dry the solid at 35 °C and -0.09 MPa for 5 h to obtain a cobalt-based porous organic cage bifunctional catalyst.

[0033] Example 2: This embodiment discloses a preparation process for trans-4-methylcyclohexyl isocyanate. The raw materials for preparing trans-4-methylcyclohexyl isocyanate include, by weight: 105g trans-4-methylcyclohexylamine, 15g cobalt-based porous organic cage bifunctional catalyst, 35g triethyl orthoformate, 10g 5Å molecular sieve, 400g organic solvent, 2.5g boron trifluoride diethyl ether complex, and 1.5g triphenyl phosphite. The organic solvent is N-methylpyrrolidone.

[0034] The preparation process of trans-4-methylcyclohexyl isocyanate includes the following steps: S1. Raw material preparation: Take trans-4-methylcyclohexylamine, organic solvent, boron trifluoride diethyl ether complex and triphenyl phosphite, and stir at 200 r / min for 45 min to obtain homogeneous mixture A; Cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and 5Å molecular sieve were mixed and dispersed in an organic solvent and ultrasonically treated at an ultrasonic power of 210W for 30 min to obtain a uniform suspension B. The organic solvent used to prepare mixture A and the organic solvent used to prepare suspension B are from the same system, and their mass ratio is 3.5:1. S2, Continuous flow carbonylation reaction: The microreactor system was purged with high-purity nitrogen for 35 minutes to remove air and moisture from the system, and then the mixture A and suspension B were preheated to 50°C. Preheated mixture A was pumped into the microreactor system at a flow rate of 5 mL / min, and preheated suspension B was pumped into the microreactor system at a flow rate of 1.5 mL / min. A mass flow controller was used to control the feeding of carbon dioxide at a stoichiometric rate of 1.2 equivalents (molar ratio of carbon dioxide to trans-4-methylcyclohexylamine was 1.2:1). The carbonylation reaction was carried out under the action of a cobalt-based porous organic cage bifunctional catalyst. The pressure was controlled at 0.6 MPa, the residence time at 35 min, and the reaction temperature was controlled in three stages: 80℃ in the initial stage, 85℃ in the middle stage, and 90℃ in the final stage. The characteristic peak of NCO (2270 cm⁻¹) was monitored by online infrared spectroscopy. -1 When the intensity of the NCO characteristic peak no longer changes significantly with time (i.e., the rate of change is ≤1% / min), the reaction is considered to have reached its endpoint. S3. Product separation and purification: After the reaction solution was cooled to 30°C, it was then centrifuged at 10,000 r / min for 20 min to separate the cobalt-based porous organic cage bifunctional catalyst and the 5 Å molecular sieve. The recovered cobalt-based porous organic cage bifunctional catalyst was washed three times with anhydrous ethanol, filtered, and dried at 85°C and a vacuum of -0.10 MPa (gauge pressure) for 8 h. It can be reused. After being reused five times, the relative initial catalytic activity retention rate is ≥88%; the cobalt residue in the product is ≤0.5 ppm (detected by inductively coupled plasma mass spectrometry (ICP-MS)). The supernatant enters a falling film evaporator and is subjected to distillation at 90°C and a vacuum of -0.098 MPa (gauge pressure) to recover the organic solvent and triethyl orthoformate. The residue is then distilled in a short-path molecular distillation apparatus under the following conditions: First stage: Removal of low-boiling-point substances at 110℃ and 20Pa; Second stage: 135℃, 3Pa, collect the main fraction (trans-4-methylcyclohexyl isocyanate).

[0035] The preparation method of cobalt-based porous organic cage bifunctional catalyst includes the following steps: 1) Synthesis of porous organic cage framework: Under nitrogen protection, 11 g of trialdehyde phloroglucinol and 17.5 g of (R,R)-1,2-diaminocyclohexane were ultrasonically dispersed and dissolved in 320 mL of 1,2-dichloroethane and 22 mL of acetic acid. The ultrasonic power was 160 W and the ultrasonic time was 35 min. After dissolution, the mixture was transferred to a reaction vessel under nitrogen protection and refluxed at 75°C for 48 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered to collect the solid, washed four times with methanol (110 mL each time), and then dried for 14 h at 85 °C and a vacuum of -0.11 MPa (gauge pressure) to obtain a chiral porous organic cage. 2) Cobalt-based active site loading: 7g of chiral porous organic cage was dispersed in 220mL of anhydrous ethanol and stirred at 180r / min for 35min under nitrogen protection. 10.5 g of cobalt chloride hexahydrate and 1.3 g of 4-dimethylaminopyridine were added and reacted at 65 °C for 24 h. After centrifugation at 8500 r / min for 18 min, the solid was washed four times with anhydrous ethanol and then dried at 65 °C and a vacuum of -0.11 MPa for 10 h to obtain a cobalt-based porous organic cage intermediate. 3) Introduction of acidic sites: The cobalt-based porous organic cage intermediate was mixed with trifluoromethanesulfonic acid silica gel with a loading of 10 wt% at a mass ratio of 1.2:1, and then added to an agate ball mill jar. The mixture was ball milled at 320 r / min for 2.5 h. Add 55 mL of anhydrous diethyl ether, stir for 12 min, filter to remove free acid, and dry the solid at 45 °C and -0.11 MPa for 7 h to obtain a cobalt-based porous organic cage bifunctional catalyst.

[0036] Example 3: This embodiment discloses a preparation process for trans-4-methylcyclohexyl isocyanate. The raw materials for preparing trans-4-methylcyclohexyl isocyanate include, by weight: 100g trans-4-methylcyclohexylamine, 11g cobalt-based porous organic cage bifunctional catalyst, 28g triethyl orthoformate, 7g 5Å molecular sieve, 300g organic solvent, 1.5g tri(pentafluorophenyl)borane, and 0.9g triphenyl phosphite. The organic solvent is a mixture of dimethylacetamide and dimethyl carbonate in a volume ratio of 3:1.

[0037] The preparation process of trans-4-methylcyclohexyl isocyanate includes the following steps: S1. Raw material preparation: Trans-4-methylcyclohexylamine, organic solvent, tris(pentafluorophenyl)borane and triphenyl phosphite were stirred at 175 r / min for 36 min to obtain homogeneous mixture A. Cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and 5Å molecular sieve were mixed and dispersed in an organic solvent and ultrasonically treated at an ultrasonic power of 200W for 25min to obtain a uniform suspension B. The organic solvent used to prepare mixture A and the organic solvent used to prepare suspension B are from the same system, and their mass ratio is 3:1. S2, Continuous flow carbonylation reaction: The microreactor system was purged with high-purity nitrogen for 30 minutes to remove air and moisture from the system, and then the mixture A and suspension B were preheated to 45°C. Preheated mixture A was pumped into the microreactor system at a flow rate of 4 mL / min, and preheated suspension B was pumped into the microreactor system at a flow rate of 1.2 mL / min. A mass flow controller was used to control the feeding of carbon dioxide at a stoichiometric ratio of 1.1 equivalents (molar ratio of carbon dioxide to trans-4-methylcyclohexylamine was 1.1:1). The carbonylation reaction was carried out under the action of a cobalt-based porous organic cage bifunctional catalyst. The pressure was controlled at 0.5 MPa, the residence time at 28 min, and the reaction temperature was controlled in three stages: 77℃ in the first stage, 83℃ in the middle stage, and 88℃ in the final stage. The characteristic peak of NCO (2270 cm⁻¹) was monitored by online infrared spectroscopy. -1 When the intensity of the NCO characteristic peak no longer changes significantly with time (i.e., the rate of change is ≤1% / min), the reaction is considered to have reached its endpoint. S3. Product separation and purification: After the reaction solution was cooled to 28°C, it was then centrifuged at 9000 r / min for 17 min to separate the cobalt-based porous organic cage bifunctional catalyst and the 5 Å molecular sieve. The recovered cobalt-based porous organic cage bifunctional catalyst was washed three times with anhydrous ethanol, filtered, and dried at 80°C and a vacuum of -0.095 MPa (gauge pressure) for 7 h. It can be reused. After being reused five times, the relative initial catalytic activity retention rate is ≥88%; the cobalt residue in the product is ≤0.5 ppm (detected by inductively coupled plasma mass spectrometry (ICP-MS)). The supernatant enters a falling film evaporator and is subjected to distillation at 85°C and a vacuum of -0.096 MPa (gauge pressure) to recover the organic solvent and triethyl orthoformate. The residue is then distilled in a short-path molecular distillation apparatus under the following conditions: First stage: Removal of low-boiling-point substances at 105℃ and 15Pa; Second stage: 130℃, 2Pa, collect the main fraction (trans-4-methylcyclohexyl isocyanate).

[0038] The preparation method of cobalt-based porous organic cage bifunctional catalyst includes the following steps: 1) Synthesis of porous organic cage framework: Under nitrogen protection, 10 g of trialdehyde phloroglucinol and 16.5 g of (R,R)-1,2-diaminocyclohexane were ultrasonically dispersed and dissolved in 300 mL of 1,2-dichloroethane and 20 mL of acetic acid. The ultrasonic power was 150 W and the ultrasonic time was 30 min. After dissolution, the mixture was transferred to a reaction vessel under nitrogen protection and refluxed at 72°C for 42 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered to collect the solid, washed three times with methanol (100 mL each time), and then dried for 12 h at 80 °C and a vacuum of -0.10 MPa (gauge pressure) to obtain a chiral porous organic cage. 2) Cobalt-based active site loading: Disperse 6g of chiral porous organic cage in 200mL of anhydrous ethanol and stir at 165r / min for 30min under nitrogen protection. Add 9.5g of cobalt chloride hexahydrate and 1.2g of 4-dimethylaminopyridine, react at 62℃ for 22h, centrifuge at 8000r / min for 15min, wash the solid three times with anhydrous ethanol, and then dry at 60℃ and vacuum degree -0.10MPa for 8h to obtain cobalt-based porous organic cage intermediate. 3) Introduction of acidic sites: The cobalt-based porous organic cage intermediate was mixed with trifluoromethanesulfonic acid silica gel with a loading of 9 wt% at a mass ratio of 1.1:1, and then added to an agate ball mill jar. The mixture was ball milled at 300 r / min for 2 h. Add 50 mL of anhydrous diethyl ether, stir for 10 min, filter to remove free acid, and dry the solid at 40 °C and -0.10 MPa for 6 h to obtain a cobalt-based porous organic cage bifunctional catalyst.

[0039] Comparative Example 1: A process for preparing trans-4-methylcyclohexyl isocyanate differs from Example 3 only in that the cobalt-based porous organic cage bifunctional catalyst is replaced with a porous organic cage supported rhodium bifunctional catalyst (the cobalt chloride hexahydrate in the preparation of the cobalt-based porous organic cage bifunctional catalyst is replaced with rhodium trichloride trihydrate, and the rhodium loading of the catalyst is 3.0 wt%).

[0040] Comparative Example 2: A preparation process for trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that the organic solvent is replaced with a perfluorinated tertiary amine (PFT).

[0041] Comparative Example 3: A preparation process for trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that the organic solvent is replaced with N,N-dimethylformamide (DMF).

[0042] Comparative Example 4: A preparation process for trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that the dehydrating agent (a composite system of triethyl orthoformate and 5Å molecular sieve) is replaced with a single triethyl orthoformate (5Å molecular sieve).

[0043] Comparative Example 5: A process for preparing trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that the reaction pressure (0.5 MPa) in step S2 is increased to 1.5 MPa.

[0044] Comparative Example 6: A preparation process for trans-4-methylcyclohexyl isocyanate differs from Example 3 only in that, in step 3) of the cobalt-based porous organic cage bifunctional catalyst preparation method, the acidic sites are prepared by liquid-phase dropwise addition. Specifically, the cobalt-based porous organic cage intermediate is dispersed in a mixed solvent to form a suspension. A trifluoromethanesulfonic acid silica gel dispersion (or trifluoromethanesulfonic acid dilution) is slowly added dropwise to the suspension at a rate of 0.5-1.0 mL / min. The mixture is stirred at 25-35°C, aged at 40-50°C for 2-4 h, centrifuged at 8500 r / min for 15 min, washed four times with methanol, and dried under vacuum of -0.11 MPa to obtain a bifunctional catalyst with both cobalt-based active sites and acidic sites.

[0045] Comparative Example 7: A process for preparing trans-4-methylcyclohexyl isocyanate differs from Example 3 only in that a batch reactor is used instead of a continuous flow microreactor.

[0046] Comparative Example 8: A process for preparing trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that the cobalt-based porous organic cage bifunctional catalyst is replaced with cobalt chloride hexahydrate (without POC loading).

[0047] Comparative Example 9: A preparation process for trans-4-methylcyclohexyl isocyanate, which differs from Example 3 only in that tris(pentafluorophenyl)borane (an auxiliary agent) is not added.

[0048] The trans-4-methylcyclohexyl isocyanates obtained in Examples 1-3 and Comparative Examples 1-9 were tested for product purity and isomer ratio, product yield, feed conversion rate, moisture content, color, NCO content, storage stability (NCO retention rate), reactivity (coupled with glimepiride synthesis), solvent recovery rate, catalyst recycling performance, catalyst acidity, heavy metal residue, energy consumption per unit product, and waste generation. The testing methods and standards for each performance are as follows: 1. Product purity and isomer ratio: Gas chromatography-mass spectrometry (GC-MS) was used, in accordance with SN / T4675.10-2016, with optimized column combination and temperature program conditions. The instrument was an Agilent 8890-5977B, equipped with FID and MSD. The chromatographic column was an HP-5MS (30m×0.25mm×0.25μm) connected in series with a chiral Beta-DEX 120 column (30m×0.25mm×0.25μm). The injection port temperature was 280℃, the detector temperature was 300℃, and the temperature program was as follows: 60℃ for 2 min, increased to 200℃ at 10℃ / min and held for 5 min, then increased to 240℃ at 5℃ / min and held for 10 min. The trans isomer ratio was calculated using the area normalization method: trans peak area / (trans + cis) peak area × 100%.

[0049] 2. Product yield: Quantitative analysis was performed using gas chromatography with internal standard method, in accordance with GB / T 32263-2015 General Rules for Gas Chromatography Analysis of Trace Impurities in High-Purity Chemicals; the internal standard was n-eicosane (purity ≥99.9%); the calculation formula was yield (%) = (actual weight of product / theoretical yield) × 100%. The actual weight of the product was determined by gas chromatography with internal standard method, and the theoretical yield was calculated based on 100% conversion of trans-4-methylcyclohexylamine to the target product.

[0050] 3. Raw material conversion rate: High performance liquid chromatography (HPLC) was used, according to GB / T 27576-2011 General Rules for High Performance Liquid Chromatography Analysis of Essential Oils; the instrument was a Waters Alliance e2695 equipped with a PDA detector; the chromatographic column was an Agilent ZORBAX SB-C18 (250mm×4.6mm, 5μm); the mobile phase was acetonitrile-water (65:35, v / v), the flow rate was 1.0mL / min, and the detection wavelength was 210nm; the calculation formula was conversion rate (%) = (1 - area of ​​amine peak after reaction / area of ​​amine peak before reaction) × 100%.

[0051] 4. Moisture content: The Karl Fischer coulometric method was used, according to GB / T 6283-2008 Determination of Moisture Content in Chemical Products by Karl Fischer Method (General Method); the instrument was a Mettler Toledo C30 coulometric moisture analyzer; the sample amount was 1.0 g, titrated to the endpoint.

[0052] 5. Colorimetry (APHA): The platinum-cobalt colorimetric method was used, according to GB / T 605-2006 General Method for Determination of Colorimetry of Chemical Reagents; the instrument was a Hach DR3900 spectrophotometer; the absorbance was measured at a wavelength of 410 nm, and the standard curve was used as a reference.

[0053] 6. NCO content: The di-n-butylamine method was used, according to "GB / T 12009.4-2016 Aromatic Isocyanates for Polyurethane Production - Part 4: Determination of Isocyanate Content"; the reagents were 0.1 mol / L di-n-butylamine toluene solution and 0.1 mol / L HCl standard solution; the calculation formula was: NCO content (%) = (V blank - V sample) × C(HCl) × 4.202 / m sample × 100%.

[0054] 7. Storage stability (NCO retention rate): Seal the sample in a nitrogen-filled ampoule and place it in a 40℃ constant temperature incubator; take samples every 5 days to determine the NCO content, and calculate the retention rate (%) = (NCO content on day n / initial NCO content) × 100%.

[0055] 8. Reactivity (coupled with glimepiride synthesis): This product was used in the synthesis of glimepiride with commercially available trans-4-methylcyclohexyl isocyanate (purity 99.0%) under the same conditions; the yield and purity of glimepiride were determined by high performance liquid chromatography (HPLC) according to the Chinese Pharmacopoeia or industry standards.

[0056] 9. Solvent recovery rate: Collect the recovered solvent and determine its purity and composition by GC method according to "GB / T 32263-2015 General Rules for Gas Chromatography Analysis of Trace Impurities in High Purity Chemicals"; the calculation formula is recovery rate (%) = (weight of recovered solvent / weight of input solvent) × 100%.

[0057] 10. Catalyst recycling performance: The used catalyst is recovered and reused 5 times; the conversion rate and yield of each reaction are measured, and the activity retention rate is calculated as (conversion rate of the 5th reaction / conversion rate of the 1st reaction) × 100%.

[0058] 11. Catalyst acidity: The NH3-programmed temperature desorption method (NH3-TPD) was used, and the instrument was Micromeritics AutoChem II 2920. The conditions were optimized according to GB / T 30730-2014 Test Method for Programmed Temperature Reduction and Programmed Temperature Oxidation of Coal. The acidity was quantitatively calculated by the desorption peak area.

[0059] 12. Heavy metal residue: The ICP-MS method was used according to GB / T 30799-2014 Test Methods for Food Detergents - Determination of Heavy Metals; the instrument was an Agilent 7900; the Co residue in the product was determined.

[0060] 13. Unit product energy consumption: According to the "GB / T 2589-2020 General Rules for Calculating Comprehensive Energy Consumption", the energy consumption of the entire process, including reaction, separation, and drying, is calculated and divided by the product mass.

[0061] 14. Amount of three wastes generated: The total amount of wastewater, waste residue and waste gas generated during the reaction process is divided by the mass of the product.

[0062] The results are shown in Tables 2 and 3.

[0063] Table 2. Basic performance test results of trans-4-methylcyclohexyl isocyanates obtained in Examples 1-3 and Comparative Examples 1-9 Group Product yield (%) Raw material conversion rate (%) Product purity (GC%) trans isomer ratio (%) Moisture content (ppm) Chromaticity (APHA) NCO content (%) Heavy metal residue (ppm) Example 1 85.3 92.6 99.2 99.0 25 20 29.5 0.38 (Co) Example 2 88.7 97.3 99.5 99.3 22 18 29.8 0.42 (Co) Example 3 90.5 98.5 99.6 99.5 19 15 30.0 0.35 (Co) Comparative Example 1 94.1 99.2 99.7 99.8 18 12 30.2 0.28 (Rh) Comparative Example 2 92.8 98.9 99.6 99.6 19 13 29.9 0.36 (Co) Comparative Example 3 87.2 95.8 99.3 99.1 24 21 29.4 0.40 (Co) Comparative Example 4 83.5 91.8 99.0 98.8 32 22 29.2 0.45 (Co) Comparative Example 5 91.2 98.8 99.6 99.5 18 14 30.1 0.34 (Co) Comparative Example 6 86.9 95.6 99.2 99.0 26 20 29.3 0.41 (Co) Comparative Example 7 72.3 85.7 98.5 98.2 35 30 28.8 0.52 (Co) Comparative Example 8 65.8 79.3 97.5 97.0 40 32 28.5 1.8 (Co) Comparative Example 9 82.4 90.7 99.0 98.7 28 23 29.1 0.43 (Co) Table 3. Test results of the process performance and application performance of trans-4-methylcyclohexyl isocyanate obtained in Examples 1-3 and Comparative Examples 1-9 Group 30-day NCO retention rate (%) Glimepiride synthesis yield (%) Solvent recovery rate (%) Catalyst activity retention rate (%) after 5 cycles Energy consumption per unit product (kWh / kg) Waste generation (g / kg product) Catalyst cost (relative value) Example 1 97.2 90.1 93.5 88.2 1.48 58 1.0 Example 2 97.5 91.3 92.8 89.5 1.42 55 1.1 Example 3 97.8 92.5 92.2 90.8 1.35 52 0.8 Comparative Example 1 98.2 93.1 92.3 92.6 1.22 45 10.0 Comparative Example 2 97.9 92.8 90.8 91.0 1.32 49 8.3 Comparative Example 3 97.0 90.5 91.5 87.6 1.45 60 0.9 Comparative Example 4 96.8 89.2 92.0 88.0 1.40 62 1.0 Comparative Example 5 97.7 92.2 92.1 90.5 1.41 51 0.8 Comparative Example 6 96.9 90.0 92.2 87.6 1.38 53 1.0 Comparative Example 7 95.6 88.5 88.2 75.3 2.85 98 1.0 Comparative Example 8 94.3 87.8 91.8 68.5 1.50 72 0.7 Comparative Example 9 96.7 88.8 92.0 85.5 1.42 59 0.9 Using Example 3 as the control group, the performance differences and causes of Comparative Examples 1-9 are analyzed as follows: (a) Comparative examples of catalysts and auxiliaries (Comparative Examples 1, 6, 8, and 9) Comparative Example 1 (Porous organic cage supported rhodium bifunctional catalyst): Product yield increased from 90.5% to 94.1%, an increase of 4.0%; feed conversion increased from 98.5% to 99.2%, an increase of 0.7%; and the proportion of trans isomers increased from 99.5% to 99.8%, an increase of 0.3%. This is because rhodium has slightly higher catalytic activity than Co, but rhodium is a scarce and precious metal. Although rhodium-based catalysts have slightly better catalytic performance, their cost is too high, making them unsuitable for industrial application.

[0064] Comparative Example 6 (Preparation of acidic sites by liquid-phase dropwise addition): The product yield decreased from 90.5% to 86.9%, a decrease of 3.9%; the catalyst activity retention rate after 5 cycles decreased from 90.8% to 87.6%, a decrease of 3.2%. The reason is that the liquid-phase dropwise addition method leads to uneven distribution and partial agglomeration of acidic sites, resulting in a decrease in dehydration efficiency compared to the ball milling composite process. This shifts the reaction equilibrium towards the feedstock, ultimately leading to a decrease in product yield.

[0065] Comparative Example 8 (without POC loading): Product yield decreased significantly from 90.5% to 65.8%, a decrease of 27.3%; raw material conversion rate decreased from 98.5% to 79.3%, a decrease of 19.2%; trans isomer proportion decreased from 99.5% to 97.0%, a decrease of 2.5%; Co residue increased from 0.35 ppm to 1.8 ppm. The reason is the lack of confined space and chiral environment provided by POC, the absence of confined loading by porous organic cages, and the fact that cobalt chloride hexahydrate is a soluble salt easily dissolved in the organic solvent of the reaction system. Continuous centrifugation could not completely separate soluble cobalt ions, resulting in a significant excess of cobalt residue in the product (1.8 ppm), which does not meet the heavy metal residue requirements for pharmaceutical intermediates.

[0066] Comparative Example 9 (without additives): Product yield decreased from 90.5% to 82.4%, a decrease of 8.9%; raw material conversion rate decreased from 98.5% to 90.7%, a decrease of 7.8%. The reason is that the additive tris(pentafluorophenyl)borane can synergistically activate carbon dioxide molecules with cobalt-based active sites, reducing the activation energy barrier of C=O bonds in carbon dioxide; without additives, the activation efficiency of carbon dioxide decreased significantly, the rate-controlling step of the carbonylation reaction was hindered, resulting in a simultaneous decrease in raw material conversion rate and product yield.

[0067] (ii) Comparative examples of solvent systems (Comparative Examples 2 and 3) Comparative Example 2 (solvent: perfluorotertiary amine PFT): Product yield increased from 90.5% to 92.8%, an increase of 2.3%; reaction rate increased by 15%. The reason is that the strong electron-withdrawing effect of PFT can further activate carbon dioxide, but the solvent cost and industrial application cost are relatively high.

[0068] Comparative Example 3 (DMF solvent): Product yield decreased from 90.5% to 87.2%, a decrease of 3.3%; feed conversion rate decreased from 98.5% to 95.8%, a decrease of 2.7%. The reason is that DMF has lower solubility for carbon dioxide than DMAC and a weaker stabilizing effect on intermediates, leading to the decomposition of some intermediates and a slight decrease in yield.

[0069] (III) Comparative examples of dewatering system and process parameters (Comparative examples 4, 5, and 7) Comparative Example 4 (Triethyl Orthoformate): The product yield decreased from 90.5% to 83.5%, a decrease of 7.0%; the moisture content increased from 19 ppm to 32 ppm, an increase of 68.4%. The reason is that without the physical adsorption assistance of molecular sieves, the chemical dehydrating agent could not remove trace amounts of moisture in time, resulting in a leftward shift of the reaction equilibrium and partial hydrolysis of the product.

[0070] Comparative Example 5 (1.5 MPa pressure): Product yield increased from 90.5% to 91.2%, an increase of 0.7%; raw material conversion rate increased from 98.5% to 98.8%, an increase of 0.3%. The reason is that carbon dioxide solubility increases slightly under high pressure, but the pressure requirement is high, equipment investment increases by 30%, and energy consumption increases.

[0071] Comparative Example 7 (batch reactor): Product yield decreased significantly from 90.5% to 72.3%, a decrease of 20.1%; energy consumption per unit product increased from 1.35 kWh / kg to 2.85 kWh / kg, an increase of 111.1%; and waste generation increased from 52 g / kg product to 98 g / kg product, an increase of 88.5%. This is because batch reactors lack the enhanced mass and heat transfer structure of microreactors, resulting in low mass and heat transfer efficiency. This leads to uneven dispersion of carbon dioxide in the reaction system, prolonged reaction time, increased side reactions, and a significant increase in energy consumption and waste emissions.

[0072] In summary, trans-4-methylcyclohexylamine provides amino sites as a reactant, the cobalt-based porous organic cage bifunctional catalyst can catalyze the carbonylation reaction efficiently, triethyl orthoformate and 5Å molecular sieve work together to dehydrate and promote the forward shift of the reaction equilibrium, organic solvents ensure the dissolution and dispersion of each raw material and intermediate, and auxiliaries and stabilizers help improve the reaction stability.

[0073] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for preparing trans-4-methylcyclohexyl isocyanate, characterized in that, Includes the following steps: S1. Raw material preparation: A homogeneous mixture A is obtained by mixing trans-4-methylcyclohexylamine, organic solvent, auxiliaries and stabilizers; a suspension B is obtained by mixing and dispersing cobalt-based porous organic cage bifunctional catalyst, triethyl orthoformate and 5Å molecular sieve in an organic solvent and ultrasonically treating it. S2, Continuous flow carbonylation reaction: Mixture A, suspension B and carbon dioxide are continuously fed into the microreactor system, and the carbonylation reaction is carried out under the action of cobalt-based porous organic cage bifunctional catalyst. The reaction temperature is 75-90℃, the pressure is 0.4-0.6MPa, and the residence time is 20-35min. S3. Product separation and purification: The reaction solution is separated by solid-liquid separation to recover the cobalt-based porous organic cage bifunctional catalyst. The supernatant is distilled to recover the organic solvent and triethyl orthoformate. The residue is molecularly distilled to obtain trans-4-methylcyclohexyl isocyanate.

2. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1, characterized in that, The raw materials for preparing trans-4-methylcyclohexyl isocyanate, by weight, include: 95-105 parts of trans-4-methylcyclohexylamine, 8-15 parts of cobalt-based porous organic cage bifunctional catalyst, 20-35 parts of triethyl orthoformate, 5-10 parts of 5Å molecular sieve, 200-400 parts of organic solvent, 0.8-2.5 parts of additives, and 0.3-1.5 parts of stabilizer. The molar ratio of carbon dioxide to trans-4-methylcyclohexylamine is (1.0-1.2):

1.

3. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1 or 2, characterized in that, The organic solvent is a mixture of dimethylacetamide, N-methylpyrrolidone, or dimethylacetamide and dimethyl carbonate in a volume ratio of (2.8-3.2):

1.

4. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1 or 2, characterized in that, The auxiliary agent is tris(pentafluorophenyl)borane or boron trifluoride diethyl ether complex; the stabilizer is triphenyl phosphite.

5. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1 or 2, characterized in that, The preparation method of cobalt-based porous organic cage bifunctional catalyst includes the following steps: 1) Under nitrogen protection, trialdehyde phloroglucinol and (R,R)-1,2-diaminocyclohexane were ultrasonically dispersed and dissolved in 1,2-dichloroethane and acetic acid. After dissolution, the mixture was transferred to a reaction vessel under nitrogen protection and refluxed at 70-75°C for 36-48 h. After washing and drying, a chiral porous organic cage was obtained. 2) Disperse the chiral porous organic cage in anhydrous ethanol, add cobalt chloride hexahydrate and 4-dimethylaminopyridine, react at 60-65℃ for 20-24h, and obtain the cobalt-based porous organic cage intermediate by centrifugation, washing and drying. 3) The cobalt-based porous organic cage intermediate was ball-milled with silica gel trifluoromethanesulfonate, washed with ether, and then vacuum dried to obtain a cobalt-based porous organic cage bifunctional catalyst.

6. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 5, characterized in that, In step 1), the amount of trialdehyde phloroglucinol used is 9.0-11.0g, the amount of (R,R)-1,2-diaminocyclohexane used is 15.0-17.5g, the amount of 1,2-dichloroethane used is 280-320mL, and the amount of acetic acid used is 18-22mL; the power of ultrasonic dispersion and dissolution is 140-160W, and the ultrasonic time is 25-35min; the washing process uses methanol to wash 2-4 times, with a single washing volume of 90-110mL; the drying conditions are: temperature 75-85℃, vacuum degree -0.09~-0.11MPa, and time 10-14h.

7. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 5, characterized in that, In step 2), the amount of chiral porous organic cage is 5.0-7.0 g, the amount of cobalt chloride hexahydrate is 8.5-10.5 g, and the amount of 4-dimethylaminopyridine is 1.1-1.3 g; the centrifugation speed is 7500-8500 r / min, and the centrifugation time is 12-18 min; the washing process uses anhydrous ethanol to wash 2-4 times; the drying conditions are: temperature 55-65℃, vacuum degree -0.09~-0.11 MPa, and time 6-10 h.

8. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 5, characterized in that, In step 3), the loading of trifluoromethanesulfonic acid in the trifluoromethanesulfonic acid silica gel is 8wt%-10wt%, the mass ratio of cobalt-based porous organic cage intermediate to trifluoromethanesulfonic acid silica gel is (1.0-1.2):1, the ball milling speed is 280-320 r / min, and the ball milling time is 1.5-2.5 h; the vacuum drying conditions are: temperature 35-45℃, vacuum degree -0.09~-0.11 MPa, and time 5-7 h.

9. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1, characterized in that, In step S1, the organic solvent used to prepare mixture A is the same system as the organic solvent used to prepare suspension B, and the mass ratio of the two is (2.5-3.5):

1. During the preparation of mixture A, the mixture is stirred at a speed of 150-200 r / min for 30-45 min. The ultrasonic treatment conditions for preparing suspension B are: ultrasonic power 190-210 W, treatment time 20-30 min.

10. The preparation process of trans-4-methylcyclohexyl isocyanate according to claim 1, characterized in that, In step S2, the pumping rate of mixture A is 2-5 mL / min, and the pumping rate of suspension B is 0.8-1.5 mL / min; both mixture A and suspension B are preheated before being introduced into the microreactor system at a preheating temperature of 40-50℃; the main reactor uses three-stage temperature control: 75-80℃ in the first stage, 80-85℃ in the middle stage, and 85-90℃ in the last stage; the reaction endpoint is determined by online infrared monitoring of the NCO characteristic peak. In step S3, solid-liquid separation is performed using a continuous centrifuge at a speed of 8000-10000 r / min; distillation recovery is carried out at 80-90℃ and a vacuum of -0.095 to -0.098 MPa; molecular distillation is performed in two stages: the first stage removes low-boiling substances at 100-110℃ and 10-20 Pa, and the second stage collects the main fraction at 125-135℃ and 1-3 Pa.

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