Mandelic acid borneol ester synthesized by borneol and mandelic acid and method

Abstract

The invention discloses a mandelic acid borneol ester synthesized by borneol and mandelic acid and a method, and belongs to the technical field of deep processing of forest chemical products. The method comprises the following steps: adding borneol, mandelic acid, a catalyst and a water-carrying agent into a reaction kettle, stirring, and controlling the reaction temperature and the reaction time to obtain a liquid product; after the reaction is finished, cooling to room temperature, adding water, washing at room temperature, and collecting washing water; carrying out reduced pressure distillation on the collected oil layer, and recovering the water-carrying agent; pouring the product without the water-carrying agent into a storage tank, adding anhydrous MgSO4, and standing overnight to obtain a bornyl mandelate crude product; and carrying out fractionation on the obtained borneol mandelate crude product, and removing unreacted borneol and borneol dehydration byproducts to obtain refined borneol mandelate. The product obtained by the method is high in yield, high in purity and easy to separate, the used catalyst has the characteristics of being high in catalytic activity, simple to prepare, non-toxic and low in corrosivity, and industrial production is easy to realize.

Description

Technical Field

[0001] The invention belongs to the technical field of deep processing of forest chemical products, and particularly relates to borneol mandelate synthesized from borneol and mandelic acid and a method thereof. Background Art

[0002] Borneol is a natural active product with diverse pharmacological activities and good development prospects. It can change the structure of the blood-brain barrier, cornea, skin and other mucous membranes, and promote other drugs to reach the site of action through these structures. However, in long-term clinical use, borneol is not suitable for single synthetic preparations and long-term continuous use due to its volatility and toxicity. In order to better exert the medicinal value of borneol, a series of examples represented by new synthetic drugs such as tacrine-bornyl ester have proved that chemical modification can enhance the efficacy of the parent drug and reduce the toxicity of the parent drug.

[0003] Esterification is commonly used in the modification and modification of borneol structure, such as the synthesis of danshensu acyl alanyl proline bornyl ester, danshensu bornyl ester, catechin bornyl ester, gallic acid bornyl ester, benzoic acid bornyl ester, caffeic acid bornyl ester and ibuprofen bornyl ester, which can reduce the toxicity of borneol and enhance its own effects. Journal of Pharmaceutical Research, Vol. 39, No. 4, 2020, disclosed the use of the prodrug principle to synthesize borneol esters with natural active molecules or finished drugs, and found that it can reduce the toxicity of borneol and enhance its own effects. Due to the large steric hindrance, the synthesis of these bornyl esters often requires a condensation agent: for example, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) are used as condensation agents to synthesize danshensu acyl-L-alanyl-L-proline bornyl ester; 1,3-dicyclohexylcarbodiimide (DDC) is used as a condensation agent to synthesize gallic acid bornyl ester. The Journal of Guangzhou University of Chinese Medicine published in Volume 38, Issue 4, 2021 that the maximum yield of synthesizing 3,5-dinitrobenzoic acid bornyl ester using 4-toluenesulfonic acid as a catalyst is only 62%, which is a low yield problem.

[0004] The disclosure of the above background technology content is only used to assist in understanding the inventive concept and technical solution of the present invention. It does not necessarily belong to the prior art of this patent application. In the absence of clear evidence that the above content has been disclosed on the filing date of this patent application, the above background technology should not be used to evaluate the novelty and creativity of the present application. Summary of the invention

[0005] The present invention provides a method for synthesizing borneol mandelate from borneol and mandelic acid. 2 O 3 or ZrB 2Catalyzing the esterification of borneol and preparing borneol mandelate, a target product with high yield, high purity and easy separation is obtained, which has the advantages of simple process, less three wastes discharge, low cost and green environmental protection. It can solve the problems that borneol is easy to volatilize in clinical medication, easy to lose in the production and storage of preparations, which affects the quality and efficacy of the preparations, and has certain toxic and side effects.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0007] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0008] (1) Add borneol, mandelic acid, catalyst and water-carrying agent in a molar ratio of 1:1-3:0.05-0.3:0.3-1.5 into a reaction kettle, stir, control the reaction temperature to 60-130°C and the reaction time to 4-8h, and obtain a liquid product; the catalyst is boric acid, B 2 O 3 , ZrB 2 One or more of the following;

[0009] (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;

[0010] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0011] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.5-1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0012] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0013] Furthermore, the catalyst in step (1) is a mixture of boric acid or boron oxide and ZrB 2 The composition has a mass ratio of 1:0.5-0.8.

[0014] Furthermore, the catalyst in step (1) is boric acid, boron oxide and ZrB 2 , the mass ratio is 1:0.3-0.5:0.2-0.5.

[0015] Furthermore, the water-carrying agent in step (1) includes one or more of benzene, toluene, xylene, cyclohexane, and chloroform.

[0016] Furthermore, 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 mandelic acid is 95-98%; the concentrated mandelic acid and catalyst are dissolved in the water-carrying agent and reused as the raw materials of step (1).

[0017] Furthermore, the water-carrying agent is toluene and chloroform, and the mass ratio thereof is 1-2:1.

[0018] Further, in step (4), the anhydrous MgSO 4 The mass of the product is 0.5-1%.

[0019] Furthermore, 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.

[0020] Further, the distillate at the fractionation port temperature of 160-170° C. is collected.

[0021] Compared with the prior art, the present invention has the following technical advantages:

[0022] 1. The method of the present invention uses borneol and mandelic acid as raw materials, and catalyzes borneol and mandelic acid to synthesize borneol mandelate for the first time, thereby obtaining a high-yield, high-purity and easily separable product.

[0023] 2. The method of the present invention uses a highly active catalyst, and boric acid, B 2 O 3 , ZrB 2 One or more of the above are used as catalysts to better promote the conversion of borneol into borneol mandelate and improve the product yield.

[0024] 3. The method of the present invention adds a water-carrying agent chloroform / methane to the borneol and mandelic acid raw materials, so that the water generated by the reaction forms a "low azeotropic" substance with chloroform / methane and is evaporated, so that the equilibrium of the esterification reaction is shifted to the right, thereby improving the equilibrium conversion rate.

[0025] 4. The method of the present invention can obtain borneol mandelate with higher purity. In Example 10, the content of borneol mandelate fine product is as high as 99.6%, and the yield is 86.3%, which is 24.3% higher than the highest yield (62.0%) of 3,5-dinitrobenzoic acid bornyl ester disclosed in the Journal of Guangzhou University of Chinese Medicine in Volume 38, Issue 4, 2021.

[0026] 5. The method of the present invention also recycles excess mandelic acid and catalyst for reuse, and the effect of repeated use is better. At the same time, the method has the advantages of simple process, less three wastes, low cost, green environmental protection, etc., which is conducive to industrial promotion and application.

[0027] 6. The borneol mandelate prepared by the method of the present invention enhances the efficacy of the parent drug and reduces the toxicity caused by the parent drug by chemically modifying borneol. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The present invention is a flow chart of a method for synthesizing borneol mandelate from borneol and mandelic acid. DETAILED DESCRIPTION

[0029] 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.

[0030] like Figure 1 As shown, a method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0031] (1) Add borneol, mandelic acid, catalyst and water-carrying agent in a molar ratio of 1:1-3:0.05-0.3:0.3-1.5 into a reaction kettle, stir, control the reaction temperature to 60-130°C and the reaction time to 4-8h, and obtain a liquid product; the catalyst is boric acid, B 2 O 3 , ZrB 2 One or more of the following;

[0032] (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;

[0033] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0034] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.5-1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0035] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0036] Furthermore, the catalyst in step (1) is a mixture of boric acid or boron oxide and ZrB 2 The composition has a mass ratio of 1:0.5-0.8.

[0037] The catalyst described in step (1) is boric acid, boron oxide and ZrB 2 , the mass ratio is 1:0.3-0.5:0.2-0.5.

[0038] The water-carrying agent in step (1) includes one or more of benzene, toluene, xylene, cyclohexane, and chloroform.

[0039] 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 mandelic acid is 95-98%; the concentrated mandelic acid and catalyst are dissolved in the water-carrying agent and reused as the raw materials of step (1).

[0040] The water-carrying agent is toluene and chloroform, and the mass ratio thereof is 1-2:1.

[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 160-170°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 method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0048] (1) adding borneol, mandelic acid, boric acid and toluene in a molar ratio of 1:1.0:0.15:1 into a reaction kettle, stirring, controlling the reaction temperature to 120° C. and the reaction time to 5 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 4 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) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.5% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0052] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0053] The GC content of borneol mandelate obtained in this example is 82.4%, and the GC content of borneol mandelate after purification is 96.8%. The yield of borneol mandelate fine product reaches 75.3%.

[0054] Example 2

[0055] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0056] (1) adding borneol, mandelic acid, boric acid and chloroform in a molar ratio of 1:1.5:0.15:0.8 into a reaction kettle, stirring, controlling the reaction temperature to 70° C. and the reaction time to 6 h, to obtain a liquid product;

[0057] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, 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;

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

[0059] (4) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 0.8% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0060] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0061] The GC content of borneol mandelate obtained in this example is 83.5%, and the GC content of borneol mandelate after purification is 97.8%. The yield of borneol mandelate fine product reaches 78.5%.

[0062] Example 3

[0063] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0064] (1) adding borneol, mandelic acid, boric acid and chloroform in a molar ratio of 1:2:0.1:0.5 into a reaction kettle, stirring, controlling the reaction temperature to 70° C. and the reaction time to 4 h, to obtain a liquid product;

[0065] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.5 times the amount of water as 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) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0068] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0069] The GC content of borneol mandelate obtained in this example is 81.8%, and the GC content of borneol mandelate after purification is 95.7%. The yield of borneol mandelate fine product reaches 73.8%.

[0070] Example 4

[0071] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0072] (1) adding borneol, mandelic acid, boric acid and toluene in a molar ratio of 1:2.5:0.2:1.5 into a reaction kettle, stirring, controlling the reaction temperature to 120° C. and the reaction time to 6 h, to obtain a liquid product;

[0073] (2) After the reaction of 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;

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

[0075] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.6% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0076] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0077] The GC content of borneol mandelate obtained in this example is 82.3%, and the GC content of borneol mandelate after purification is 96.6%. The yield of borneol mandelate fine product is 74.9%.

[0078] Example 5

[0079] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0080] (1) adding borneol, mandelic acid, boric acid and chloroform in a molar ratio of 1:3.0:0.05:1.2 into a reaction kettle, stirring, controlling the reaction temperature to 70° C. and the reaction time to 7 h, to obtain a liquid product;

[0081] (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;

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

[0083] (4) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0084] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0085] The GC content of borneol mandelate obtained in this example is 78.1%, and the GC content of borneol mandelate after purification is 94.3%. The yield of borneol mandelate fine product reaches 70.6%.

[0086] Example 6

[0087] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0088] (1) adding borneol, mandelic acid, boric acid and toluene in a molar ratio of 1:1.8:0.15:0.5 into a reaction kettle, stirring, controlling the reaction temperature to 125° C. and the reaction time to 5 h, to obtain a liquid product;

[0089] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.5 times the amount of water as the product is added, and the mixture is washed three 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) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0092] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0093] The GC content of borneol mandelate obtained in this example is 85.7%, and the GC content of borneol mandelate after purification is 98.5%. The yield of borneol mandelate fine product reaches 83.3%.

[0094] Example 7

[0095] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0096] (1) adding borneol, mandelic acid, zirconium boride and chloroform in a molar ratio of 1:1.5:0.20:1.0 into a reaction kettle, stirring, controlling the reaction temperature to 75° C. and the reaction time to 7 h, to obtain a liquid product;

[0097] (2) After the reaction in step (1) is completed, the mixture is cooled to room temperature, 1.2 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;

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

[0099] (4) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 0.8% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0100] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0101] The GC content of borneol mandelate obtained in this example is 50.9%, and the GC content of borneol mandelate after purification is 90.6%. The yield of borneol mandelate fine product is 47.9%.

[0102] Example 8

[0103] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0104] (1) adding borneol, mandelic acid, boric oxide and chloroform in a molar ratio of 1:1.5:0.10:1.0 into a reaction kettle, stirring, controlling the reaction temperature to 75° C. and the reaction time to 6 h, to obtain a liquid product;

[0105] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.0 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;

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

[0107] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.6% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0108] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0109] The GC content of borneol mandelate obtained in this example is 82.2%, and the GC content of borneol mandelate after purification is 95.9%. The yield of borneol mandelate fine product is 74.5%.

[0110] Example 9

[0111] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0112] (1) adding borneol, mandelic acid, boric acid, zirconium boride and chloroform in a molar ratio of 1:1.5:0.10:0:02:1.0 into a reaction kettle, stirring, controlling the reaction temperature to 75°C and the reaction time to 6 hours, to obtain a liquid product;

[0113] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.0 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;

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

[0115] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.5% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0116] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0117] The GC content of borneol mandelate obtained in this example is 86.6%, and the GC content of borneol mandelate after purification is 99.1%. The yield of borneol mandelate fine product is 84.7%.

[0118] Example 10

[0119] A method for synthesizing borneol mandelate from borneol and mandelic acid comprises the following steps:

[0120] (1) adding borneol, mandelic acid, boric acid, boron oxide, zirconium boride, and chloroform in a molar ratio of 1:1.5:0.10::0.01:0.02:1.0 into a reaction kettle, stirring, controlling the reaction temperature to 75°C and the reaction time to 7 hours, to obtain a liquid product;

[0121] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.0 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;

[0122] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0123] (4) Pour the product from step (3) after removing the water-containing agent into a storage tank, and add 0.5% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0124] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0125] The GC content of borneol mandelate obtained in this example is 88.9%, and the GC content of borneol mandelate after purification is 99.6%. The yield of borneol mandelate fine product is 86.3%.

[0126] Comparative Example 1

[0127] (1) adding borneol, mandelic acid and toluene in a molar ratio of 1:1.5:1.0 into a reaction kettle, stirring, controlling the reaction temperature to 120° C. and the reaction time to 6 h, to obtain a liquid product;

[0128] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.5 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;

[0129] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0130] (4) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 1% of the product mass of anhydrous MgSO 4 After being left to stand overnight, a crude product of borneol mandelate was obtained.

[0131] The GC content of bornyl mandelate in the product obtained in this comparative example is 0%.

[0132] Comparative Example 2

[0133] The operation steps are basically the same as those in Comparative Example 1, except that borneol and B are used in step (1). 2 O 3 At a mass ratio of 1:0.10, the GC content of the obtained borneol mandelate is 82.9%.

[0134] Comparative Example 3

[0135] 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 mandelate is 60.3%.

[0136] Table 1 shows the crude content of borneol mandelate and the refined content of borneol mandelate prepared in Examples 1-10

[0137]

[0138]

[0139] In the detailed discussion of Examples 1-10, the synthesis process of borneol mandelate shows excellent efficiency and high yield under the joint action of three catalysts. This achievement not only reflects the exquisiteness of chemical synthesis technology, but also the direct application of in-depth understanding of the catalytic reaction mechanism. By accurately controlling the reaction temperature, the present invention cleverly utilizes the effect of temperature on the speed of molecular motion, so that the frequency of collisions of reactant molecules increases, the number of activated molecules increases, and then accelerates the occurrence of effective collisions, directly improving the reaction rate. It is worth noting that the selectivity of the reaction is not sacrificed in this process, that is, the generation of borneol mandelate occupies a dominant position, and its fine product content is maintained at more than 90%, which fully demonstrates the high accuracy of catalyst design and the ability to optimize reaction conditions.

[0140] Particularly worth mentioning is the technical highlight in Example 10, in which the fine product content of borneol mandelate reaches an astonishingly high 99.6%. The achievement of this achievement is inseparable from the fine control of reaction conditions and the innovative application of purification technology. By further optimizing parameters such as reaction time, temperature, catalyst dosage, and adopting advanced separation and purification methods, by-products and impurities are effectively removed, and the high-purity preparation of borneol mandelate is achieved. This significant technological progress not only enhances the market competitiveness of the product, but also provides a purer raw material basis for subsequent application research.

[0141] In addition, the success of this series of experiments also reflects the in-depth practice of the concept of green chemistry. By selecting environmentally friendly catalysts and solvents and recycling them, the generation of harmful by-products is reduced, the impact on the environment is reduced, and a win-win situation of economic benefits and environmental protection is achieved. In summary, the synthesis of borneol mandelate in Examples 1-10 is not only an important breakthrough in chemical synthesis technology, but also a vivid example of significant technological progress in the fields of green chemistry and efficient catalysis.

[0142] In order to investigate the catalytic effect of different catalysts on the synthesis of borneol mandelate, borneol mandelate was synthesized using a commonly used sulfuric acid catalyst and compared with a blank test. The test results are shown in Table 2.

[0143] Table 2 is a comparison of the experimental results of different catalysts in Comparative Examples 1-3

[0144]

[0145] As shown in Table 2, when we explore the reaction characteristics of mandelic acid and borneol in a catalyst-free environment, we deeply analyze the basic principles of chemical reactions. In the absence of a catalyst, the molecules of these two compounds lack sufficient activation energy to overcome the reaction barrier, so they remain relatively stable and do not undergo significant chemical reactions. This phenomenon deeply reveals the importance of catalysts in promoting organic synthesis reactions, that is, by reducing the reaction activation energy, reactions that are not easy to occur can be carried out under mild conditions.

[0146] The research then focused on comparing two different types of catalysts - traditional, highly corrosive sulfuric acid and the emerging B 2 O 3 (boron trioxide) in the catalytic esterification reaction of mandelic acid and borneol. Sulfuric acid, as a traditional catalyst, is widely used in a variety of chemical syntheses due to its strong acidity and wide reactivity, but in Comparative Example 3, its significant corrosiveness not only increases the danger of experimental operation, but also may have an adverse effect on the reaction product, such as causing an increase in side reactions and a darkening of the product color, which directly affects the purity of the product and subsequent application potential.

[0147] In contrast, B 2 O 3 As a new type of catalyst, it exhibits more excellent catalytic performance. Its unique surface structure and chemical properties enable it to effectively adsorb and activate mandelic acid and borneol molecules, reducing the activation energy required for the esterification reaction between them. This efficient catalytic mechanism not only accelerates the reaction rate, but also significantly improves the yield and purity of the target product, mandelic acid borneol ester. Specifically, B 2 O 3The content of borneol mandelate obtained under catalysis is 22.6% higher than that under sulfuric acid catalysis conditions. This significant technological advancement not only improves production efficiency, but also reduces production costs, providing a more economical and environmentally friendly option for industrial production.

[0148] In addition, B 2 O 3 The non-corrosive nature of the catalyst is also a major highlight. This means that during the reaction process, it can reduce corrosion damage to the equipment, extend the service life of the equipment, and reduce the safety threat to operators, making the entire production process safer and more controllable.

[0149] In summary, B 2 O 3 The application of this catalyst in the esterification of mandelic acid and borneol is not only an important technological innovation for traditional sulfuric acid catalysts, but also reflects the significant trend of the modern chemical industry moving towards high efficiency, green and sustainable development. This discovery not only enriches the theoretical system of organic catalytic chemistry, but also opens up a new path for industrial production and application research in related fields.

[0150] The catalyst reuse test adopted in Example 6: A process for synthesizing borneol mandelate from borneol, recovered mandelic acid and a catalyst comprises the following steps:

[0151] (1) Add borneol and mandelic acid in a molar ratio of 1:1, the recovered mandelic acid and catalyst, and toluene with water to a reaction kettle and stir (the amount of borneol and water toluene is consistent with the amount added in Example 6), stir, control the reaction temperature to 125° C., and the reaction time to 5 h to obtain a liquid product;

[0152] (2) After the reaction of step (1) is completed, the mixture is cooled to room temperature, 1.5 times the amount of water as the product is added, and the mixture is washed three times at room temperature, and the washing water is collected;

[0153] (3) subjecting the oil layer collected in step (2) to vacuum distillation to recover the water-carrying agent;

[0154] (4) Pour the product after removing the water-containing agent in step (3) into a storage tank and add 1% of the product mass of anhydrous MgSO 4 After being left overnight, a crude product of borneol mandelate was obtained;

[0155] (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

[0156] The test results of using the recovered mandelic acid and catalyst twice in succession in Example 6 are shown in Table 3.

[0157] Table 3 Test results of two consecutive uses of the recovered mandelic acid and catalyst used in Example 6

[0158]

[0159] As can be seen from Table 3, after the catalyst used in Example 6 was reused twice, the crude borneol mandelate content dropped from 85.7% to only 75.6%, which shows that the catalyst still has a relatively high catalytic activity.

[0160] 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 method for synthesizing borneol mandelate from borneol and mandelic acid, characterized in that: The steps include: (1) adding borneol, mandelic acid, catalyst and water-carrying agent in a molar ratio of 1:1-3:0.05-0.3:0.3-1.5 into a reaction kettle, stirring, controlling the reaction temperature to 60-130°C and the reaction time to 4-8h, to obtain a liquid product; the catalyst is one or more of boric acid, B2O3 and ZrB2; (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-containing agent removed into a storage tank, adding anhydrous MgSO4 and leaving overnight to obtain a crude product of borneol mandelate; (5) fractionating the crude borneol mandelate obtained in step (4) to remove unreacted borneol and borneol dehydration by-products to obtain refined borneol mandelate.

2. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 1, characterized in that: The catalyst described in step (1) is composed of boric acid or boron oxide and ZrB2, and the mass ratio thereof is 1:0.5-0.

8.

3. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 1, characterized in that: The catalyst described in step (1) is boric acid, boron oxide and ZrB2, and the mass ratio thereof is 1:0.3-0.5:0.2-0.

5.

4. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 1, characterized in that: The water-carrying agent in step (1) includes one or more of benzene, toluene, xylene, cyclohexane, and chloroform.

5. The method for synthesizing borneol mandelate from borneol and mandelic acid 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 mandelic acid is 95-98%; the concentrated mandelic acid and catalyst are dissolved in the water-carrying agent and reused as the raw materials of step (1).

6. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 5, characterized in that: The water-carrying agent is toluene and chloroform, and the mass ratio thereof is 1-2:

1.

7. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 1, characterized in that: The mass of anhydrous MgSO4 described in step (4) is 0.5-1% of the mass of the product.

8. The method for synthesizing borneol mandelate from borneol and mandelic acid 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.

9. The method for synthesizing borneol mandelate from borneol and mandelic acid according to claim 8, characterized in that: The distillate was collected when the distillation port temperature was 160-170°C.

10. Bornyl mandelate synthesized according to the method according to any one of claims 1 to 9.

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