Process for synthesizing borneol glycolate from borneol, glycollic acid and methyl glycolate

Abstract

The invention discloses a process for synthesizing borneol glycolate from borneol, glycollic acid and methyl glycolate, which comprises the following steps: (1) adding borneol, glycollic acid, methyl glycolate, a catalyst and a water-carrying agent into a reaction kettle for reaction to obtain a liquid product; (2) after the reaction in the step (1) is finished, cooling to room temperature, adding water, washing at room temperature, and collecting washing water; (3) carrying out reduced pressure distillation on the oil layer collected in the step (2), and recovering the water-carrying agent; (4) pouring the product without the water-carrying agent in the step (3) into a storage tank, adding anhydrous MgSO4, and standing overnight to obtain a crude product of the bornyl glycolate; and (5) fractionating the crude product of the bornyl glycolate obtained in the step (4), and removing unreacted borneol and borneol dehydration byproducts to obtain a high-purity refined product of the bornyl glycolate. The method has the advantages of simple process, low cost, environmental protection and the like, and is beneficial to industrial popularization and application.

Description

Technical Field

[0001] The invention belongs to the technical field of deep processing of forest chemical products, and particularly relates to a process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate. Background Art

[0002] Borneol, also known as borneol, is one of the earliest organic drug ingredients used in nature. Its pharmacological effects are extensive and far-reaching, covering anti-inflammatory and analgesic, anti-myocardial ischemia, brain protection, and promoting drug penetration. In the field of traditional Chinese medicine, borneol is often used as an adjuvant drug in prescriptions to enhance the efficacy of the main and auxiliary drugs, and to guide the drugs directly to the lesions to improve the overall therapeutic effect. However, due to its inherent high volatility and potential toxicity, borneol is not suitable for long-term use alone.

[0003] In order to fully explore and optimize the medicinal potential of borneol, researchers have demonstrated the possibility of enhancing the efficacy of the parent drug while reducing its toxicity through chemical modification methods, such as the successful synthesis of new compounds such as tacrine-bornyl ester. The core of this strategy lies in the esterification method, which uses the principle of prodrug design to create borneol ester, a borneol derivative. After entering the body, borneol ester can gradually release the parent drug and borneol, which not only solves the problem that borneol is difficult to prepare directly due to its volatility, but also effectively reduces its toxic side effects, further enhancing the therapeutic efficacy.

[0004] It is worth noting that the Journal of Pharmaceutical Research, Vol. 39, No. 4, 2020, reported in detail the research progress of combining borneol with natural active molecules or existing drugs using prodrug strategies to form borneol esters. These results significantly reduced the toxicity of borneol and enhanced its efficacy. In addition, due to the particularity of the molecular structure of borneol esters, condensation agents are often required in its synthesis process. For example, EDCI (1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride) and DMAP (4-dimethylaminopyridine) played a key role in the synthesis of danshensu acyl-L-alanyl-L-proline borneol esters; while DDC (1,3-dicyclohexylcarbodiimide) was used in the synthesis of gallic acid borneol esters in different studies.

[0005] According to the Journal of Guangzhou University of Chinese Medicine, Vol. 38, No. 4, 2021, 4-toluenesulfonic acid was used as a catalyst to successfully synthesize 3,5-dinitrobenzoic acid bornyl ester with a maximum yield of 62%. This achievement further enriched the synthesis and application research of bornyl ester compounds and opened up a new way for the widespread application of bornyl in the field of modern medicine. However, there is still a problem of low yield, which cannot meet higher requirements. Summary of the invention

[0006] The present invention provides a process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate, so as to solve the problems that borneol is easy to volatilize in clinical medication, easy to lose in the preparation production and storage process, that is, affecting the quality and efficacy of the preparation, and having certain toxic and side effects. The method of the present invention can obtain a target product with high yield, high purity and easy separation, and has the advantages of simple process, less three wastes discharge, low cost, green environmental protection, etc.

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0008] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0009] (1) Adding borneol, glycolic acid, methyl glycolate, a catalyst, and a water-carrying agent into a reactor in a certain proportion, reacting for 3-7 hours at a stirring speed of 200-300 rpm and a reaction temperature of 60-125° C. to obtain a liquid product; the molar ratio of borneol, glycolic acid, and methyl glycolate is 1:1-4:1-1.5; the mass ratio of borneol to catalyst is 1:0.1-0.3; the mass ratio of reactants to water-carrying agent is 1:0.5-2.0; the catalyst comprises one or both of boric acid and boric oxide;

[0010] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 0.5-1.5 times of water is added to the product, and the mixture is washed 3-5 times at room temperature, and the washing water is collected;

[0011] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0012] (4) pouring the product from step (3) with the water removed into a storage tank, adding 0.5-1% of the mass of the product anhydrous MgSO4 and leaving it overnight to obtain a crude product of borneol glycolate;

[0013] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0014] Preferably, the catalyst in step (1) further comprises T i B2, wherein boric acid or boric oxide is mixed with T i The mass ratio of B2 is 1:0.5-0.8.

[0015] Preferably, the catalyst in step (1) is boric acid, boron oxide and T i B2, the mass ratio is 1:0.3-0.5:0.2-0.5.

[0016] Preferably, the molar ratio of borneol, glycolic acid and methyl glycolate in step (1) is 1:1.0-3.5:1.0-1.5.

[0017] More preferably, the molar ratio of borneol, glycolic acid and methyl glycolate in step (1) is 1:2.0:1.0.

[0018] Preferably, the water-carrying agent in step (1) comprises one or more of benzene, toluene, xylene, cyclohexane and chloroform.

[0019] Preferably, the mass ratio of the reactant to the water-carrying agent in step (1) is 1:1.2-1.5.

[0020] Preferably, the reaction temperature in step (1) is 70-75° C. for 4-7 hours.

[0021] Preferably, the washing water in step (2) is subjected to rotary evaporation at a vacuum degree of -0.1 MPa and a temperature of 80-85° C. to remove water until the mass concentration of glycolic acid is 85-90%; the concentrated glycolic acid solution is dissolved in methyl glycolate and reused as the raw material of step (1).

[0022] Preferably, the fractionation in step (5) needs to be carried out in an oil bath with a vacuum degree of -0.09 to -0.1 MPa, and the distillate is collected when the fractionation port temperature is 135-140°C.

[0023] Compared with the prior art, the present invention has the following technical advantages:

[0024] (1) This innovative process cleverly uses borneol and glycolic acid as raw materials to create a pioneering catalytic synthesis of borneol glycolate. This process not only achieves a high yield and purity of the product, but also greatly simplifies the separation process.

[0025] (2) In the process of promoting this synthesis reaction, the present invention introduces a high-efficiency catalyst, which includes boric acid, boron oxide, T i One or more of B2, their addition acts as a leader among catalysts, significantly accelerating the conversion efficiency of borneol to borneol glycolate, thereby increasing the yield of the final product.

[0026] (3) In order to further optimize the reaction pathway, the present invention innovatively introduces water-carrying agents such as chloroform or toluene, which combine with the water generated in the reaction to form an easily evaporated "low-azeotropic" complex, effectively removing water molecules from the reaction system and causing the esterification reaction equilibrium to shift toward the product, thereby achieving a significant increase in conversion rate.

[0027] (4) The process of the present invention can obtain borneol glycolate with a relatively high purity. In the example verification (such as Example 9), the present invention successfully prepared borneol glycolate with a purity of up to 98.1%, demonstrating the significant advantages of the present technology.

[0028] (5) In addition, this method can also recycle excess glycolic acid, methyl glycolate and catalyst for repeated use twice, and the reuse effect is good. The simplicity of the process, the low emission of three wastes, the high cost-effectiveness and the sustainability of green environmental protection have paved a solid road for large-scale industrial application and demonstrated broad market prospects and social value.

[0029] (6) Borneol glycolate prepared by the process of the present invention enhances the efficacy of the parent drug and reduces the toxicity of the parent drug by chemically modifying borneol. The process of the present invention effectively solves the problems that borneol is easy to volatilize in clinical medication, is easy to lose during preparation production and storage, affects the quality and efficacy of the preparation, and has certain toxic and side effects. DETAILED DESCRIPTION

[0030] To further explain the technical means and effects of the present invention, the technical solution of the present invention is further described below in conjunction with the embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.

[0031] In an embodiment of the present invention, a process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0032] (1) Adding borneol, glycolic acid, methyl glycolate, a catalyst, and a water-carrying agent into a reactor in a certain proportion, reacting for 3-7 hours at a stirring speed of 200-300 rpm and a reaction temperature of 60-125° C. to obtain a liquid product; the molar ratio of borneol, glycolic acid, and methyl glycolate is 1:1-4:1-1.5; the mass ratio of borneol to catalyst is 1:0.1-0.3; the mass ratio of reactants to water-carrying agent is 1:0.5-2.0; the catalyst comprises one or both of boric acid and boric oxide;

[0033] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 0.5-1.5 times of water is added to the product, and the mixture is washed 3-5 times at room temperature, and the washing water is collected;

[0034] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0035] (4) pouring the product from step (3) with the water removed into a storage tank, adding 0.5-1% of the mass of the product anhydrous MgSO4 and leaving it overnight to obtain a crude product of borneol glycolate;

[0036] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0037] The catalyst in step (1) also includes T i B2, wherein boric acid or boric oxide is mixed with T i The mass ratio of B2 is 1:0.5-0.8.

[0038] The catalyst described in step (1) is boric acid, boron oxide and T i B2, the mass ratio is 1:0.3-0.5:0.2-0.5.

[0039] The water-carrying agent described in step (1) includes one or more of benzene, toluene, xylene, cyclohexane, and chloroform.

[0040] The washing water in step (2) is subjected to rotary evaporation at a vacuum degree of -0.1 MPa and a temperature of 80-85°C to remove water until the mass concentration of glycolic acid is 85-90%; the concentrated glycolic acid solution is dissolved in methyl glycolate and reused as the raw material of step (1).

[0041] The fractionation described in step (5) needs to be carried out in an oil bath with a vacuum degree of -0.09 to -0.1 MPa, and the distillate is collected when the fractionation port temperature is 135-140°C.

[0042] Sample analysis test:

[0043] Aglient7890A gas chromatograph, Agilent, USA; chromatographic column: AT-35, quartz capillary column (60m×0.25mm×0.25μm). GC analysis conditions: carrier gas, high-purity nitrogen; program temperature: 70℃ (2min), increase to 150℃ at 50℃ / min, stay for 3min, increase to 230℃ at 30℃ / min, stay for 30min; injection port temperature: 250℃, total flow rate 130.5mL / min, split ratio 50:1, septum purge 3mL / min; FID detection, detection port temperature: 250℃, hydrogen flow rate 40mL / min, air 450mL / min, nitrogen purge, 25mL / min. Injection volume 0.2uL.

[0044] The content of each component was obtained from the gas chromatogram using the area normalization method.

[0045] In order to make the disclosure of the present invention more complete, it is described below through more specific embodiments.

[0046] Example 1

[0047] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0048] (1) borneol, glycolic acid, methyl glycolate, boric acid, and toluene were added into a reaction kettle in a ratio of 1:1.0:1.5:0.15:1.5, and the mixture was reacted at a stirring speed of 300 rpm and a reaction temperature of 122° C. for 6 h to obtain a liquid product;

[0049] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 0.5 times the amount of water as the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0050] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0051] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0052] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0053] The GC content of borneol glycolate obtained in this example is 60.7%; the GC content of borneol glycolate after purification is 92.3%.

[0054] Example 2

[0055] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0056] (1) borneol, glycolic acid, methyl glycolate, boric acid, and chloroform were added into a reaction kettle in a ratio of 1:1.5:1.0:0.2:1.0, and the mixture was reacted for 5 h at a stirring speed of 250 rpm and a reaction temperature of 72° C. to obtain a liquid product;

[0057] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, 0.8 times the amount of water as the product is added, and the mixture is washed 4 times at room temperature, and the washing water is collected;

[0058] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0059] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 0.8% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0060] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0061] The GC content of borneol glycolate obtained in this example is 56.3%; the GC content of borneol glycolate after purification is 89.5%.

[0062] Example 3

[0063] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0064] (1) borneol, glycolic acid, methyl glycolate, boric acid, and chloroform were added into a reaction kettle in a ratio of 1:2.0:1.2:0.1:0.8, and the mixture was reacted for 4 hours at a stirring speed of 280 rpm and a reaction temperature of 72° C. to obtain a liquid product;

[0065] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed three times at room temperature, and the washing water is collected;

[0066] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0067] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0068] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0069] The GC content of borneol glycolate obtained in this example is 54.8%; the GC content of borneol glycolate after purification is 88.7%.

[0070] Example 4

[0071] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0072] (1) borneol, glycolic acid, methyl glycolate, boric acid, and toluene were added into a reaction kettle in a ratio of 1:3.0:1.5:0.25:2.0, and the mixture was reacted for 3 hours at a stirring speed of 220 rpm and a reaction temperature of 122° C. to obtain a liquid product;

[0073] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 0.5 times the amount of water as the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0074] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0075] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0076] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0077] The GC content of borneol glycolate obtained in this example is 52.9%; the GC content of borneol glycolate after purification is 86.4%.

[0078] Example 5

[0079] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0080] (1) borneol, glycolic acid, methyl glycolate, boric acid, and chloroform were added into a reaction kettle in a ratio of 1:3.5:1.0:0.18:1.2, and the mixture was stirred at 200 rpm and 70° C. for 7 h to obtain a liquid product;

[0081] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, 0.8 times the amount of water as the product is added, and the mixture is washed 4 times at room temperature, and the washing water is collected;

[0082] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0083] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 0.8% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0084] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0085] The GC content of borneol glycolate obtained in this example is 66.5%; the GC content of borneol glycolate after purification is 95.8%.

[0086] Example 6

[0087] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0088] (1) borneol, glycolic acid, methyl glycolate, boric acid, and toluene were added into a reaction kettle in a ratio of 1:2.5:1.5:0.3:1.8, and the mixture was reacted for 4 hours at a stirring speed of 270 rpm and a reaction temperature of 122° C. to obtain a liquid product;

[0089] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 4 times at room temperature, and the washing water is collected;

[0090] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0091] (4) pouring the product from step (3) with the water removed into a storage tank, adding 0.6% of the mass of the product anhydrous MgSO4 and leaving it overnight to obtain a crude product of borneol glycolate;

[0092] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0093] The GC content of borneol glycolate obtained in this example is 65.2%; the GC content of borneol glycolate after purification is 94.6%.

[0094] Example 7

[0095] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0096] (1) adding borneol, glycolic acid, methyl glycolate, titanium boride and chloroform into a reaction kettle in a ratio of 1:2.0:1.0:0.2:1.0, stirring at a speed of 300 rpm and a reaction temperature of 75° C. for 7 h to obtain a liquid product;

[0097] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0098] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0099] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0100] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0101] The GC content of borneol glycolate obtained in this example is 47.5%; the GC content of borneol glycolate after purification is 83.2%.

[0102] Example 8

[0103] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0104] (1) adding borneol, glycolic acid, methyl glycolate, boric acid, titanium boride, and chloroform into a reaction kettle in a ratio of 1:2.0:1.0:0.1:0.02:1.0, and reacting for 7 hours at a stirring speed of 300 rpm and a reaction temperature of 75° C. to obtain a liquid product;

[0105] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0106] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0107] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0108] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0109] The GC content of borneol glycolate obtained in this example is 70.6%; the GC content of borneol glycolate after purification is 96.3%.

[0110] Example 9

[0111] A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate comprises the following steps:

[0112] (1) adding borneol, glycolic acid, methyl glycolate, boric acid, boric acid, boron oxide, titanium boride, and chloroform into a reaction kettle in a ratio of 1:2.0:1.0:0.1:0.02:0.02:1.0, and reacting for 7 hours at a stirring speed of 300 rpm and a reaction temperature of 75° C. to obtain a liquid product;

[0113] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0114] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0115] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0116] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0117] The GC content of borneol glycolate obtained in this example is 73.7%; the GC content of borneol glycolate after purification is 98.1%.

[0118] Comparative Example 1

[0119] (1) adding borneol, glycolic acid, methyl glycolate and toluene into a reaction kettle in a ratio of 1:3.0:1.0:1.2, and reacting at a stirring speed of 300 rpm and a reaction temperature of 122° C. for 7 h to obtain a liquid product;

[0120] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 5 times at room temperature, and the washing water is collected;

[0121] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0122] (4) pouring the product from step (3) with the water removed into a storage tank, adding anhydrous MgSO4 at 1% by mass of the product and leaving it overnight to obtain a crude product of borneol glycolate;

[0123] The GC content of bornyl glycolate obtained in this comparative example is 0%.

[0124] Comparative Example 2

[0125] The operation steps are basically the same as those of Comparative Example 1, except that in step (1), borneol and B2O3 are used in a mass ratio of 1:0.10, and the GC content of the obtained borneol glycolate is 59.4%.

[0126] Comparative Example 3

[0127] The operation steps are basically the same as those of Comparative Example 1, except that in step (1), borneol and sulfuric acid are used in a mass ratio of 1:0.10, and the GC content of the obtained borneol glycolate is 38.2%.

[0128] Table 1 shows the crude borneol glycolate content and the refined borneol glycolate content prepared in Examples 1-9

[0129]

[0130] As shown in the data analysis in detail in Table 1, borneol glycolate shows a high degree of controllability and optimization potential under the synergistic effect of three catalysts. In Example 9, by finely controlling the reaction conditions, including borneol and glycolic acid, methyl glycolate in molar ratio, borneol and boric acid, boron oxide and titanium boride in mass ratio, reactants and water-carrying agent chloroform in mass ratio, speed, reaction temperature and reaction time, etc., a significant improvement in the content of borneol glycolate fine products is achieved, reaching an astonishingly high 98.1%. This achievement is not only a major breakthrough in traditional synthesis methods, but also reflects the possibility of greatly improving product purity through fine control in complex chemical reaction systems. From a theoretical perspective, the acquisition of this high-purity product may be attributed to the precise control of the delicate balance of interaction between the components in the reaction system, so that the reaction path is more inclined to generate the target product and reduce the generation of by-products.

[0131] In addition, as a class of compounds with specific biological activity and application value, the high-purity synthesis of borneol glycolate is not only of great value for basic scientific research, but also provides a more reliable and efficient source of raw materials for fields such as drug synthesis, fragrance manufacturing and materials science.

[0132] Therefore, the high-purity synthesis technology demonstrated in Example 9 has undoubtedly laid a solid foundation for the further development of related fields, and has stimulated widespread interest in in-depth exploration of reaction mechanisms, optimization of synthesis conditions and expansion of application fields.

[0133] In order to evaluate the catalytic performance of various catalysts in the synthesis of borneol glycolate, this study selected widely used sulfuric acid as a catalyst for control experiments, and set up a blank test without adding any catalyst as a benchmark. The experimental results are summarized in Table 2. Through comparative analysis, it aims to reveal the efficiency differences of borneol glycolate synthesis under different catalytic conditions.

[0134] Table 2 is a comparison of the experimental results of different catalysts in Comparative Examples 1-3

[0135]

[0136] From the detailed data analysis in Table 2, we can gain insight into the chemical inertness of glycolic acid and borneol in a catalyst-free environment. This observation not only reveals the non-spontaneity of the direct reaction between the two, but also emphasizes the key role of catalysts in promoting such organic transformations. Furthermore, through comparative experimental design, we selected two very different catalysts - traditional, significantly corrosive sulfuric acid, and emerging, relatively mild B2O3 (boron trioxide) to explore their effects on the esterification reaction of glycolic acid and borneol.

[0137] The experimental results show that B2O3 as a catalyst exhibits significant superiority over sulfuric acid. This finding is not only reflected in the catalytic efficiency, but also in the purity and color of the product. Specifically, although sulfuric acid as a catalyst can drive the reaction, its strong corrosiveness often leads to an increase in side reactions, which in turn affects the purity of the target product, borneol glycolate, which is manifested as a darker product color, which usually indicates the presence of impurities. In contrast, B2O3, with its unique catalytic mechanism, not only effectively reduces the occurrence of side reactions, but also significantly improves the yield of the target product. Specifically, the content of borneol glycolate is 21.2% higher under B2O3 catalysis than that under sulfuric acid catalysis.

[0138] This improvement is not only a direct verification of the optimization of catalyst selection, but also theoretically supports the profound influence of catalysts on reaction pathways and product distribution. B2O3 may promote the effective approach and bonding between glycolic acid carboxyl and borneol hydroxyl through the interaction between its surface acidic sites and reactant molecules, while inhibiting the occurrence of adverse side reactions, thereby achieving higher conversion rate and selectivity.

[0139] In summary, this study not only enriches the practical cases in the field of organic catalysis, but also provides a strong theoretical basis for the subsequent development of efficient and environmentally friendly catalysts. As the preferred catalyst for the esterification reaction of glycolic acid and borneol, B2O3's superior catalytic performance provides a valuable reference for the green and efficient development of similar complex organic syntheses.

[0140] Catalyst reuse test adopted in Example 5:

[0141] A process for synthesizing borneol glycolate from borneol, recycled glycolic acid, methyl glycolate and a catalyst comprises the following steps:

[0142] The ratio of borneol to glycolic acid was 1:1, and the recovered glycolic acid, methyl glycolate, catalyst, and chloroform with water were added to the reaction kettle for stirring (the amount of borneol and the water with water was consistent with the amount added in Example 5), the speed was 200 rpm, the reaction temperature was controlled to be 70 ° C, and the reaction time was 7h to obtain a liquid product;

[0143] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, and water 1 times the amount of the product is added, and the mixture is washed 4 times at room temperature, and the washing water is collected;

[0144] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0145] (4) pouring the product from step (3) with the water removed into a storage tank, adding 0.6% of the mass of the product anhydrous MgSO4 and leaving it overnight to obtain a crude product of borneol glycolate;

[0146] (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

[0147] The test results of using the glycolic acid, methyl glycolate and catalyst recovered in Example 5 twice in succession are shown in Table 3.

[0148] Table 3 Test results of glycolic acid, methyl glycolate and catalyst recovered in Example 5 for two consecutive uses

[0149]

[0150] As can be seen from Table 3, after the catalyst used in Example 5 was reused twice, the crude borneol glycolate content dropped from 66.5% to only 54.2%, which shows that the catalyst still has a relatively high catalytic activity.

[0151] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate, characterized in that: The steps include: (1) Adding borneol, glycolic acid, methyl glycolate, a catalyst, and a water-carrying agent into a reactor in a certain proportion, reacting for 3-7 hours at a stirring speed of 200-300 rpm and a reaction temperature of 60-125° C. to obtain a liquid product; the molar ratio of borneol, glycolic acid, and methyl glycolate is 1:1-4:1-1.5; the mass ratio of borneol to catalyst is 1:0.1-0.3; the mass ratio of reactants to water-carrying agent is 1:0.5-2.0; the catalyst comprises one or both of boric acid and boric oxide; (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 0.5-1.5 times of water is added to the product, and the mixture is washed 3-5 times at room temperature, and the washing water is collected; (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent; (4) pouring the product from step (3) with the water removed into a storage tank, adding 0.5-1% of the mass of the product anhydrous MgSO4 and leaving it overnight to obtain a crude product of borneol glycolate; (5) fractionating the crude borneol glycolate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain a high-purity borneol glycolate product.

2. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The catalyst in step (1) also includes T i B2, wherein boric acid or boric oxide is mixed with T i The mass ratio of B2 is 1:0.5-0.

8.

3. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 2, characterized in that: The catalyst described in step (1) is boric acid, boron oxide and T i B2, the mass ratio is 1:0.3-0.5:0.2-0.

5.

4. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The molar ratio of borneol, glycolic acid and methyl glycolate in step (1) is 1:1.0-3.5:1.0-1.

5.

5. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 4, characterized in that: The molar ratio of borneol, glycolic acid and methyl glycolate described in step (1) is 1:2.0:1.

0.

6. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The water-carrying agent described in step (1) includes one or more of benzene, toluene, xylene, cyclohexane, and chloroform.

7. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The mass ratio of the reactant to the water-carrying agent in step (1) is 1:1.2-1.

5.

8. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: In step (1), the reaction temperature is 70-75° C. for 4-7 hours.

9. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The washing water in step (2) is subjected to rotary evaporation at a vacuum degree of -0.1 MPa and a temperature of 80-85°C to remove water until the mass concentration of glycolic acid is 85-90%; the concentrated glycolic acid solution is dissolved in methyl glycolate and reused as the raw material of step (1).

10. The process for synthesizing borneol glycolate from borneol, glycolic acid and methyl glycolate according to claim 1, characterized in that: The fractionation described in step (5) needs to be carried out in an oil bath with a vacuum degree of -0.09 to -0.1 MPa, and the distillate is collected when the fractionation port temperature is 135-140°C.

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