A method for preparing borneol by continuously dehydrogenating isoborneol and hydrogenating

Abstract

The application discloses a method for preparing borneol by continuously dehydrogenating and hydrogenating isoborneol, which comprises the following steps: dissolving isoborneol in an organic solvent, mixing the isoborneol with hydrogen, and carrying out dehydrogenation and hydrogenation reaction in a catalytic reactor by a two-stage temperature method, so as to realize the preparation of borneol products; and the reactor is loaded with a catalyst which takes one or more of Ru, Rh, Pd, Pt, Cu, Co, Ni and Fe as an active component and takes alumina, titania or silicon oxide as a carrier. The method can improve the conversion rate of isoborneol and the yield of borneol, and the content of borneol in the obtained product meets the requirements of pharmacopoeia.

Description

Technical Field

[0001] This invention belongs to the field of chemical production, and specifically relates to a method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol. Background Technology

[0002] Borneol, also known as camphor, has the chemical formula C 10 H 18 Borneol has a bidirectional regulatory and protective effect on the central nervous system, both refreshing the mind and calming the nerves. It also helps to clear blood impurities, improves vascular permeability, and has a good inhibitory effect on hyperlipidemia, hypertension, and heart disease. Furthermore, it can improve hematopoietic function and reduce liver and kidney damage. In addition, borneol can quickly replenish water, deeply moisturize, promote apoptosis in mutated cells, induce apoptosis in cancer cells, and inhibit the occurrence and development of breast cancer, nasopharyngeal carcinoma, and lung cancer. Borneol is also used in the fragrance and cosmetics industry, where it can be used to formulate rosemary and lavender-type fragrances, and it has no toxic effects on the human body. Borneol can also be used as a cooling additive in the beverage industry. Furthermore, borneol also has mosquito-repellent, insect-repellent, and preservative properties. Borneol can be divided into natural borneol and synthetic borneol. Natural borneol is called borneol, but due to its high cost, high price, and limited resources, naturally obtained borneol can no longer meet the ever-increasing market demand. Synthetic borneol, on the other hand, has readily available and inexpensive raw materials, so many businesses use synthetic borneol to replace natural borneol. The pharmacopoeia stipulates that the borneol content in synthetic borneol must not be less than 55.0%. Under current technology, synthetic borneol produces a large amount of isoborneol. Isoborneol can be dehydrogenated to produce camphor, and camphor can be hydrogenated to produce borneol. Therefore, how to directly and effectively utilize isoborneol to produce borneol, and improve the selectivity and yield of borneol, is a problem that urgently needs to be solved.

[0003] Patent application CN101857883A discloses a method for preparing borneol using microbial strains isolated from nature. After fermentation, the cells are collected and used as a biocatalyst in an organic solvent-buffered salt system containing bornyl acetate for enzymatic hydrolysis. Following separation and purification, a borneol product with a borneol content of over 75% is obtained. Patent application CN103290065A discloses a method for preparing borneol using microorganisms isolated from nature. This method utilizes a pinene microbial process to generate bornyl acetate, followed by steam distillation to remove unreacted pinene, and finally saponification hydrolysis to prepare borneol with a borneol content of 66%-75%. Both methods are still in the research stage, are small-scale, and the space-time yield of the fermentation method is low, making large-scale application difficult.

[0004] Patent application CN110818530A discloses a method for obtaining borneol by mixing α-pinene and oxalic acid using Ag / H-ZSM-5 as a catalyst, followed by esterification after programmed heating to the reaction temperature, and then saponification, separation, and distillation. The product obtained using this method has a borneol content of over 78%. Similarly, patent application CN113683485A uses toluenesulfonic acid as a catalyst, achieving a borneol content of 77.91% in the obtained product. These methods involve vigorous exothermic reactions, poor production safety, extremely inconvenient operation, and high equipment requirements. Patent application CN104030889A discloses a method for obtaining borneol by reacting anhydrous oxalic acid with crude borneol dissolved in an organic solvent under the action of a catalyst, followed by filtration, washing, distillation, and saponification. The main characteristic of this method is that it uses the crude synthetic borneol intermediate product from the production process as the main raw material. It separates borneol and isoborneol by utilizing the difference in the rate at which they react with oxalic acid to form oxalate esters, thereby obtaining a borneol product with a content of up to 88.1%. This method is cumbersome, the separation and purification are difficult, and it has certain requirements on the initial borneol content in the crude synthetic borneol, which needs to be above 50%. These stringent conditions restrict the large-scale industrialization of synthetic borneol. Summary of the Invention

[0005] This invention provides a method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol, which has the characteristics of high yield and high selectivity. The entire process is simple, low-cost, and has less environmental pollution, and is expected to be put into industrial production.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A method for preparing borneol via continuous dehydrogenation and hydrogenation of isoborneol, using isoborneol as raw material, employing a two-stage temperature method, and carrying out a catalytic dehydrogenation and hydrogenation reaction in a catalytic reactor to prepare borneol; the method includes the following steps:

[0008] (1) Using isoborneol as a reaction raw material, isoborneol is dissolved in an organic solvent, and then the solution is mixed with hydrogen in proportion, and then reacted in a reactor containing a supported catalyst at a temperature of 140℃~200℃, and the liquid mixture after the reaction is collected.

[0009] (2) The liquid mixture collected in step (1) is used as the reaction raw material, mixed with hydrogen in proportion, and then reacted in a reactor with a supported catalyst at a temperature of 90~140℃. The resulting product is separated into gas and liquid to obtain crude borneol product.

[0010] Further, the organic solvent in step (1) includes any one or more of petroleum ether, dimethyl ether, diethyl ether, pentane, ethanol, n-heptane, butanol, and dimethyl sulfoxide.

[0011] Furthermore, in steps (1) and (2), the molar ratio of the reactants and hydrogen is 0.002235-0.02235.

[0012] Further, the active component of the supported catalyst in steps (1) and (2) is one or more of the noble metals Ru, Rh, Pd, and Pt, or one or more of the non-noble metals Cu, Co, Ni, and Fe; the support is alumina, titanium oxide, or silicon oxide; wherein the loading of the noble metal or non-noble metal is 1 to 20 wt%.

[0013] Furthermore, during the reaction processes in steps (1) and (2), the hydrogen pressure inside the reactor is 2~10 MPa.

[0014] Furthermore, during the reaction processes in steps (1) and (2), the hydrogen flow rate in the reactor is 10~100 mL / min.

[0015] Furthermore, during the reaction processes in steps (1) and (2), the flow rate of the solution in the reactor is 0.1~20 mL / min.

[0016] Furthermore, during the reaction processes in steps (1) and (2), the concentration of solute in the solution inside the reactor is 10 wt%~40 wt%.

[0017] This invention uses isoborneol as raw material, and further treats the camphor-rich product obtained by dehydrogenation in a high-temperature stage with hydrogenation in a low-temperature stage to obtain a borneol product that meets the requirements. Compared with the prior art, the method of this invention can efficiently and selectively produce the product, greatly increasing the yield of borneol, ensuring that the borneol content in the obtained product meets the pharmacopoeia requirements, and its entire process is simple, low-cost, and has less environmental pollution. Detailed Implementation

[0018] A method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol, comprising the following steps:

[0019] (1) Dissolve isoborneol in an organic solvent, and then mix the solution with hydrogen in a gas-liquid mixer using a high-pressure constant flow pump at a molar ratio of isoborneol to hydrogen of 0.002235-0.02235. Then, react the mixture in a reactor containing a supported catalyst at a temperature of 140℃~200℃, and collect the resulting liquid mixture.

[0020] (2) The liquid mixture obtained in step (1) is used as the reaction raw material and mixed in a gas-liquid mixer at a molar ratio of 0.002235-0.02235 with hydrogen. Then it is reacted in a reactor containing a supported catalyst at a temperature of 90~140℃. After gas-liquid separation, the resulting liquid product is the borneol finished product.

[0021] The organic solvent includes any one or more of petroleum ether, methyl ether, diethyl ether, pentane, ethanol, n-heptane, butanol, and dimethyl sulfoxide.

[0022] The active component of the supported catalyst is one or more of the noble metals Ru, Rh, Pd, and Pt, or one or more of the non-noble metals Cu, Co, Ni, and Fe; the support is alumina, titanium oxide, or silicon oxide; it is prepared by impregnation method, wherein the loading of noble metals or non-noble metals is 1~20 wt%.

[0023] During the reaction, the hydrogen pressure in the reactor is 2~10 MPa, the hydrogen flow rate is 10~100 mL / min, the solution flow rate is 0.1~20 mL / min, and the solute concentration in the solution is 10 wt%~40 wt%.

[0024] To make the content of this invention easier to understand, the technical solution of this invention will be further described below with reference to specific embodiments, but this invention is not limited thereto.

[0025] The catalysts used in the examples were all prepared by impregnation method. The specific steps are as follows: First, the active metal salt and the support are accurately weighed into a beaker, and water is added. The mixture is stirred at room temperature for 4 h until it is in a suspended state. Then, the suspension is heated in a 60 ℃ water bath to evaporate the water. The resulting solid is ground into powder and dried overnight in a 60 ℃ oven. The dried powder is placed in a vertical tube furnace, and 5% H2 / N2 mixed gas is introduced. The mixture is heated at 500 ℃ for 4 h for reduction. After the furnace cools to room temperature, 1% O2 / N2 mixed gas is introduced for passivation for 12 h. The resulting solid powder is stored in a vacuum for later use.

[0026] Example 1

[0027] 0.5 g of 5 wt% Cu / Al₂O₃, 1 g of isoborneol, and 40 ml of n-heptane were weighed into a high-pressure reactor. The reactor was sealed, and hydrogen gas was introduced at a certain pressure and purged 6-9 times to remove air from the reactor. The hydrogen pressure was then maintained at 3 MPa. The reaction temperature of the reactor was set to 160℃, and the stirring speed was 500 rpm. After the temperature stabilized, the timer was started, and the reaction was stopped after 8 h. The reactor was allowed to cool to room temperature, and the gas inside was released. A certain amount of the solution in the reactor was filtered through an organic membrane and subjected to gas chromatography-mass spectrometry (GC-MS) analysis. The results showed that the borneol content in the product was 2.02%, the isoborneol content was 76.35%, and the camphor content was 18.87%.

[0028] Example 2

[0029] 0.5 g of 5 wt% Co / Al₂O₃, 1 g of isoborneol, and 40 ml of n-heptane were weighed into a high-pressure reactor. The reactor was sealed, and hydrogen gas was introduced at a certain pressure and purged 6-9 times to remove air from the reactor. The hydrogen pressure was maintained at 3 MPa. The reaction temperature of the reactor was set to 160℃, and the stirring speed was 500 rpm. After the temperature stabilized, the timer was started, and the reaction was stopped after 8 h. The reactor was allowed to cool to room temperature, and the gas inside was released. A certain amount of the solution in the reactor was filtered through an organic membrane and subjected to gas chromatography quantitative analysis. The results showed that the borneol content in the product was 0.00%, the isoborneol content was 95.92%, and the camphor content was 1.26%.

[0030] Example 3

[0031] 0.5 g of 5 wt% Ni / Al₂O₃, 1 g of isoborneol, and 40 ml of n-heptane were weighed into a high-pressure reactor. The reactor was sealed, and hydrogen gas at a certain pressure was introduced and purged 6-9 times to remove air from the reactor. The hydrogen pressure was then maintained at 3 MPa. The reaction temperature of the reactor was set to 160℃, and the stirring speed was 500 rpm. After the temperature stabilized, the timer was started, and the reaction was stopped after 8 h. The reactor was allowed to cool to room temperature, and the gas inside was released. A certain amount of the solution in the reactor was filtered through an organic membrane and subjected to gas chromatography-mass spectrometry (GC-MS). The results showed that the borneol content in the product was 0.00%, the isoborneol content was 95.31%, and the camphor content was 1.95%.

[0032] Example 4

[0033] 0.5 g of 1 wt% Ru / Al₂O₃, 1 g of isoborneol, and 40 ml of n-heptane were weighed into a high-pressure reactor. The reactor was sealed, and hydrogen gas was introduced at a certain pressure and purged 6-9 times to remove air from the reactor. The hydrogen pressure was then maintained at 3 MPa. The reaction temperature in the reactor was set to 160 °C, and the stirring speed was 500 rpm. After the temperature stabilized, the timer was started, and the reaction was stopped after 8 h. The reactor was allowed to cool to room temperature, and the gas inside was released. A certain amount of the solution in the reactor was filtered through an organic membrane and subjected to gas chromatography quantitative analysis. The results showed that the borneol content in the product was 37.44%, the isoborneol content was 48.70%, and the camphor content was 11.13%.

[0034] Example 5

[0035] 0.5 g of 1 wt% Ru / Al₂O₃, 1 g of isoborneol, and 40 ml of petroleum ether were weighed into a high-pressure reactor. The reactor was sealed, and hydrogen gas was introduced at a certain pressure and purged 6-9 times to remove air from the reactor. The hydrogen pressure was then maintained at 3 MPa. The reaction temperature of the reactor was set to 160℃, and the stirring speed was 500 rpm. After the temperature stabilized, the timer was started, and the reaction was stopped after 8 h. The reactor was allowed to cool to room temperature, and the gas inside was released. A certain amount of the solution was filtered through an organic membrane and subjected to gas chromatography-mass spectrometry (GC-MS) analysis. The results showed that the borneol content in the product was 56.87%, the isoborneol content was 34.68%, and the camphor content was 5.79%.

[0036] Based on the results obtained in Examples 1-5, Ru / Al2O3 was selected as the catalyst and n-heptane as the solvent for a fixed-bed continuous reaction.

[0037] Example 6

[0038] 30 g of 1 wt% Ru / Al2O3 catalyst was weighed and loaded into a fixed-bed reactor (GHSV = 0.02 min). -1 Isobromide was dissolved in n-heptane to prepare a 20 wt% solution, which was then directly pumped into a gas-liquid mixer and mixed with hydrogen at a molar ratio of isobromide to hydrogen of 0.00447. The mixture was then passed through the reaction section of a fixed-bed reactor at 160°C (pressure 5 MPa, material flow rate 1.6 mL / min, hydrogen flow rate 50 mL / min) to achieve rapid fixed-bed dehydrogenation and hydrogenation. After the reaction stabilized, the end-of-reaction solution was collected, filtered through an organic membrane, and subjected to gas-phase quantitative analysis. The results showed that the product contained 41.82% borneol, 47.20% isobromide, and 8.29% camphor.

[0039] Example 7

[0040] 30 g of 1 wt% Ru / Al2O3 catalyst was weighed and loaded into a fixed-bed reactor (GHSV = 0.02 min). -1 Isobromide was dissolved in n-heptane to prepare a 20 wt% solution, which was then directly pumped into a gas-liquid mixer and mixed with hydrogen at a molar ratio of isobromide to hydrogen of 0.00447. The mixture was then passed through the reaction section of a fixed-bed reactor at 180°C (pressure 5 MPa, material flow rate 1.6 mL / min, hydrogen flow rate 50 mL / min) to achieve rapid fixed-bed dehydrogenation and hydrogenation. After the reaction stabilized, the end-of-reaction solution was collected, filtered through an organic membrane, and subjected to gas-phase quantitative analysis. The results showed that the product contained 52.59% borneol, 31.32% isobromide, and 13.46% camphor.

[0041] Based on the results of Examples 6 and 7, the reaction solution obtained in Example 7 was filtered for further use.

[0042] Example 8

[0043] The temperature of the fixed-bed reactor reaction section was lowered to 90 °C, while other parameters remained unchanged. The solution filtered in Example 7 was then directly pumped into a gas-liquid mixer via a high-pressure pump, where it was mixed with hydrogen at a molar ratio of 0.00447 before passing through the reactor reaction section to achieve a rapid fixed-bed hydrogenation process. After the reaction stabilized, the end-of-reaction solution was collected, filtered through an organic membrane, and subjected to quantitative gas-phase analysis. The results showed that the product contained 62.00% borneol, 35.53% isoborneol, and 0.59% camphor.

[0044] Comparative Example

[0045] Weigh 0.5 g of 1 wt% Ru / Al₂O₃, 1 g of isobath, and 40 ml of n-heptane into a high-pressure reactor. Seal the reactor and purge with hydrogen gas at a certain pressure, replacing the air 6-9 times to remove all air from the reactor. Maintain a hydrogen pressure of 3 MPa. Set the reaction temperature to 160℃ and the stirring speed to 500 rpm. Start timing after the temperature stabilizes. After 8 hours of reaction, stop heating and allow the reactor to cool to room temperature. Release the gas from the reactor. Repeat the process, purging with hydrogen gas at a certain pressure 6-9 times to remove all air from the reactor. Maintain a hydrogen pressure of 3 MPa and set the reaction temperature to 90℃ and the stirring speed to 500 rpm. Start timing after the temperature stabilizes. After 8 hours of reaction, stop heating and allow the reactor to cool to room temperature. Release the gas from the reactor. Take a sample of the solution from the reactor, filter it through an organic membrane, and perform quantitative gas chromatography analysis. The results showed that the product contained 33.28% borneol, 55.24% isoborneol, and 11.13% camphor.

[0046] The above description of the embodiments is merely for the purpose of helping to understand the method and core ideas of the present invention, and is intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. It is not intended to limit the scope of patent protection of the present invention. All equivalent changes or modifications made according to the spirit and essence of the present invention should be included within the scope of patent protection of the present invention.

Claims

1. A method for preparing borneol through continuous dehydrogenation and hydrogenation of isoborneol, characterized in that, Includes the following steps: (1) Using isoborneol as the reaction raw material, isoborneol is first dissolved in an organic solvent, and then the solution is mixed with hydrogen in proportion, and then reacted in a reactor containing a supported catalyst at a temperature of 140℃~200℃, and the liquid mixture after the reaction is collected. (2) The collected liquid mixture is used as a reaction raw material and mixed with hydrogen in proportion. Then it is reacted in a reactor with a supported catalyst at a temperature of 90~140℃. After gas-liquid separation, the liquid product is collected to obtain the borneol product. The supported catalyst is 1 wt% Ru / Al2O3.

2. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: The organic solvent in step (1) includes any one or more of petroleum ether, dimethyl ether, diethyl ether, pentane, ethanol, n-heptane, butanol, and dimethyl sulfoxide.

3. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: In steps (1) and (2), the molar ratio of the reactants and hydrogen is 0.002235-0.02235.

4. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: During the reaction in steps (1) and (2), the hydrogen pressure in the reactor is 2~10 MPa.

5. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: During the reaction in steps (1) and (2), the hydrogen flow rate in the reactor is 10~100 mL / min.

6. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: During the reaction in steps (1) and (2), the flow rate of the solution in the reactor is 0.1~20 mL / min.

7. The method for preparing borneol by continuous dehydrogenation and hydrogenation of isoborneol according to claim 1, characterized in that: During the reaction in steps (1) and (2), the solute concentration in the solution inside the reactor is 10 wt%~40 wt%.