A kind of synthetic method of boson

Abstract

The present invention belongs to the field of organic synthesis, and in particular to a method for synthesizing boson. The method for synthesizing the present invention comprises the following steps: (1) under the condition of an alkaline compound as a catalyst, using D-xylose and 3-halogenated-2,4-pentanedione as reaction raw materials, under the condition of 30-90°C, reacting for 2-8h, synthesizing intermediate A; (2) intermediate A obtained by step (1), under the action of a catalyst, is reduced by catalytic hydrogenation to obtain the target compound hydroxypropyl tetrahydropyrantriol. The reaction material cost is low, and the intermediate compound can be precipitated from the aqueous solution after generation, and the post-processing operation is simple, reducing the desalination process, and the three wastes are less produced in the production process, effectively reducing the production cost, and being relatively more green and environmentally friendly. And the yield and purity are both high, and industrial production is possible.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing bosonine. Background Art

[0002] Pro-Xylane, chemical name is hydroxypropyl tetrahydropyrantriol, CAS registration number is 439685-79-7. Pro-Xylane is a biologically active ingredient extracted from beech trees and used in cosmetics. It has the effects of promoting the production and construction of protein polysaccharides in the extracellular matrix, promoting the production of hyaluronic acid and collagen, maintaining the elasticity of the skin dermis, and anti-aging. It is currently widely used in many fields such as food, pharmaceutical chemicals, and cosmetics.

[0003] There are only a few publicly available methods for chemically synthesizing bosogenin:

[0004] 1. Patent CN110467591A route:

[0005]

[0006] The raw materials of this route are xylose and ethyl acetoacetate, and rare earth metal complexes are used as catalysts to synthesize hydroxypropyl tetrahydropyrantriol in one pot. The catalyst has a complex structure and is difficult to prepare, which makes the production cost high. The use of heavy metal catalysts may cause heavy metal residues that affect the quality of the final product.

[0007] 2. Patent CN111876452A route

[0008]

[0009] This route uses xylose and isopropanol as substrates and uses multiple enzymes to catalyze the one-pot synthesis of hydroxypropyl tetrahydropyrantriol. This method is relatively green and environmentally friendly, but the enzyme preparation used is difficult to prepare. The post-treatment enzyme removal adopts ultrafiltration, which has high requirements on equipment and complex process operation, which is not conducive to industrial production.

[0010] 3. Patent CN114105922A route:

[0011]

[0012] This route first requires the preparation of intermediate 2. The preparation process is complicated and requires an overnight reaction, which takes a long time. The reaction must be carried out at -40°C, which is a relatively harsh condition. The preparation of bosine requires the use of ligands such as Mor_DalPhos and Me-DalPhos, which are expensive and not suitable for industrial production.

[0013] In current technology, the synthesis methods of boson have the defects of long reaction time, complex reaction operation, harsh reaction conditions, high reaction cost, and being unfavorable for industrial production. Therefore, it is of great significance to develop a synthesis route of boson that is simple to operate, safe and environmentally friendly, and has an ideal yield. Summary of the invention

[0014] In order to overcome the defects of the prior art, the present invention provides a method for synthesizing bosylcan. The method uses D-xylose and 3-halogenated-2,4-pentanedione as raw materials, and obtains bosylcan through acylation reaction and reduction reaction. The method has simple preparation process, safety, environmental protection, low cost, high product purity and high yield.

[0015] The synthesis method of boson described in the present invention comprises the following steps:

[0016] (1) Under the condition of an alkaline compound as a catalyst, D-xylose and 3-halogenated-2,4-pentanedione are used as reaction raw materials, and the reaction is carried out at 30-90° C. for 2-8 hours to synthesize intermediate A;

[0017] (2) The intermediate A obtained in step (1) is reduced by catalytic hydrogenation in the presence of a catalyst to obtain the target compound hydroxypropyl tetrahydropyrantriol.

[0018] The synthetic route is as follows:

[0019]

[0020] X is a halogen, wherein the halogen is Cl, Br, or I;

[0021] In the step (1):

[0022] The catalyst is one or more of sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide;

[0023] The molar ratio of D-xylose to 3-halogenated-2,4-pentanedione is: 1:(1-2), preferably: 1:(1.1-1.3);

[0024] The reaction temperature is preferably 30-50°C;

[0025] The reaction time is preferably 4-8h;

[0026] In the step (2), the catalyst is one or more of Raney nickel, palladium / carbon, and platinum / carbon;

[0027] The mass ratio of intermediate A to catalyst is: 1: (1% to 20%), preferably: 1: (3% to 10%);

[0028] The reaction temperature is: 40-80°C, preferably 40-60°C;

[0029] The reaction time is 4-6h.

[0030] Beneficial Effects

[0031] The invention provides a new synthesis reaction for preparing bosylamine, the material cost used in the reaction is low, and halogen (Cl, Br, I) is introduced into the reaction raw materials, so that the solubility of the generated intermediate compound A is greatly reduced, and it can be directly precipitated from the aqueous solution, the reaction solution is basically free of salt, and it is not easily destroyed by the alkaline environment, and the purification post-processing operations such as resin column are omitted, the desalination process is reduced, and the three wastes are generated less in the production process, the production cost is effectively reduced, and it is relatively more green and environmentally friendly. The yield and purity are both good, and industrial production can be carried out. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is the nuclear magnetic resonance spectrum of Bose. DETAILED DESCRIPTION

[0033] Taking X=Cl as an example, the synthesis reaction route is:

[0034]

[0035] The reaction conditions in step (1) are:

[0036] 1. Preparation of intermediate A from different basic compounds:

[0037] According to the method of step (1), D-xylose and 3-chloro-2,4-pentanedione are used as reaction raw materials, the molar ratio of D-xylose:3-chloro-2,4-pentanedione is 1:1.2, the reaction is carried out at 50°C for 4 hours, and different alkaline compounds are selected as catalysts to prepare intermediate A. The amount of catalyst is a conventional amount. Taking the molar ratio of D-xylose:alkaline compound as 1:1 as an example, the results are as follows:

[0038] Basic compounds Yield purity Sodium bicarbonate 76.4％ 98.5％ Sodium carbonate 78.5％ 98.6％ Potassium carbonate 84.4％ 98.4％ Sodium hydroxide 90.2％ 98.6％ Potassium hydroxide 86.5％ 98.4％

[0039] Conclusion: The yield of intermediate A varies slightly under different alkaline catalysts, but can reach more than 75%. When sodium hydroxide or potassium hydroxide is used as the alkaline catalyst, the yield of intermediate A can reach more than 85%.

[0040] 2. Preparation of intermediate A at different temperatures:

[0041] According to the method of step (1), D-xylose and 3-chloro-2,4-pentanedione were used as reaction raw materials, the molar ratio of D-xylose:3-chloro-2,4-pentanedione was 1:1.2, the reaction was carried out at 30-90°C for 4 hours, potassium carbonate was used as a catalyst, and different reaction temperatures were selected to prepare intermediate A. The results are as follows:

[0042] temperature Yield purity 30℃ 74.2％ 98.4％ 50℃ 84.4％ 98.3％ 70℃ 75.2％ 98.1％ 90℃ 69.3％ 97.9％

[0043] Conclusion: The yield of intermediate A varies greatly under different temperature conditions. Both higher and lower temperatures are not conducive to the reaction. The yield can reach more than 74% under 30-70℃ conditions, and the purity exceeds 98%. When the temperature is 50℃, the yield of intermediate A is the highest.

[0044] 3. Preparation of intermediate A with different molar ratios of D-xylose and 3-chloro-2,4-pentanedione:

[0045] According to the method of step (1), D-xylose and 3-chloro-2,4-pentanedione were used as reaction raw materials, the reaction was carried out at 50° C. for 4 h, potassium carbonate was used as a catalyst, and different molar ratios of D-xylose and 3-chloro-2,4-pentanedione were selected to prepare intermediate A. The results are as follows:

[0046] D-xylose:3-chloro-2,4-pentanedione molar ratio Yield purity 1：1.0 80.1％ 98.2％ 1：1.2 84.4％ 98.3％ 1：1.5 82.2％ 98.5％ 1：1.8 80.8％ 98.0％ 1：2.0 76.5％ 97.8％

[0047] Conclusion: When the molar ratio of D-xylose:3-chloro-2,4-pentanedione is 1:1.0-2.0, the yield of intermediate A is above 75%, and when the molar ratio of D-xylose:3-chloro-2,4-pentanedione is 1:1.0-1.8, the yield of the intermediate can reach above 80%.

[0048] 4. Preparation of intermediate A with different reaction times:

[0049] According to the method of step (1), D-xylose and 3-chloro-2,4-pentanedione were used as reaction raw materials, reacted at 50°C for 2-8h, potassium carbonate was used as a catalyst, and the molar ratio of D-xylose to 3-chloro-2,4-pentanedione was selected to be 1:1.2 to prepare intermediate A. The results are as follows:

[0050]

[0051]

[0052] Conclusion: When the reaction time is 4-8h, the yield can reach more than 80%.

[0053] According to step (1), intermediate A is prepared under the following conditions:

[0054]

[0055] Conclusion: In step (1), when potassium hydroxide or sodium hydroxide is used as an alkaline catalyst, the molar ratio of D-xylose:3-chloro-2,4-pentanedione is 1:1.0-1.8, the temperature is 30-50°C, and the reaction time is 4-8 hours, the yield of the prepared intermediate A can reach more than 80%, and the purity is more than 98%. When sodium hydroxide is used as an alkaline catalyst, the molar ratio of D-xylose:3-chloro-2,4-pentanedione is 1:1.2-1.8, the temperature is 50°C, and the reaction time is 4-6 hours, the yield of the intermediate A is more than 85%, and the purity is more than 98%.

[0056] The reaction conditions in step (2) are:

[0057] The intermediate A obtained in step (1) is reduced by catalytic hydrogenation in the presence of a catalyst at a temperature of 40° C., a mass ratio of the intermediate A to the catalyst of 1:5%, and a reaction time of 4 h.

[0058] 1. The influence of different catalysts on the yield and purity of the final product boson:

[0059] catalyst pressure Yield purity Raney Nickel 4MPa 82.7％ 98.1％ Palladium / Carbon 2MPa 83.2％ 98.5％ Platinum / Carbon 4MPa 79.2％ 98.8％ Sodium borohydride - 76.0％ 98.0％

[0060] Conclusion: Different catalysts have little effect on the reaction, the palladium / carbon catalytic yield is slightly higher and the pressure required for the reaction is slightly lower.

[0061] 2. Effect of different mass ratios of intermediate A to catalyst on the yield and purity of the final product:

[0062] The intermediate A obtained in step (1) is reduced by catalytic hydrogenation under the action of a nickel catalyst at a temperature of 40° C. for a reaction time of 4 h:

[0063]

[0064]

[0065] Conclusion: When the catalyst dosage is 1% of the intermediate A dosage, the yield is low, and when it exceeds 10%, the yield decreases, and the product purity exceeds 98%. Therefore, the preferred mass ratio is 1:5%-10%.

[0066] 3. Effect of different reaction temperatures on the yield and purity of the final product:

[0067] The intermediate A obtained in step (1) is reduced by catalytic hydrogenation under the action of a nickel catalyst, with a catalyst dosage of 5% and a reaction time of 4 hours.

[0068] Reaction temperature Yield purity 0 73.5％ 88.1％ 20 75.3％ 88.5％ 40 82.5％ 98.4％ 60 81.5％ 98.0％ 80 79.4％ 90.7％

[0069] Conclusion: When the reaction temperature is 40-80°C, the yield of the final product can reach more than 75%, and the purity is more than 90%; when the temperature is 40-60°C, the yield of the final product can reach more than 80%, and the purity can reach more than 98%.

[0070] Embodiment 1:

[0071] 100.00 g D-xylose (0.67 mol), 56.3 g sodium bicarbonate (0.67 mol), 99.17 g 3-chloro-2,4-pentanedione (0.74 mol), and 500 g water were added to a reaction flask, heated to 50° C., and stirred for reaction for 4 h. TLC detection of the reaction solution showed that xylose had basically disappeared, and the reaction was completed. The temperature was lowered, and a brown-yellow solid was precipitated. The solid was filtered and dried in a vacuum to obtain 115 g of intermediate A with a yield of about 76.4% and a purity of 98.4%.

[0072] The intermediate A obtained above was added into an autoclave, and 5.75 g of palladium / carbon catalyst and 550 ml of methanol were added. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times, and then replaced with hydrogen three times, and the pressure was increased to 2 MPa. The airtightness of the reactor was checked, and the mixture was stirred. The temperature was raised to 40°C, and the hydrogen pressure in the autoclave was maintained at 2 MPa. The reaction was carried out for 4 hours, and the heating was turned off. The mixture was cooled to room temperature, and the gas in the autoclave was slowly discharged. The stirring was stopped, and the catalyst in the system was filtered out. The mixture was concentrated under reduced pressure to obtain 81 g of a colorless to light yellow oil, i.e., the target product, boson, with a yield of about 83.2% and a purity of 98.4%.

[0073] Embodiment 2:

[0074] 100.00 g D-xylose (0.67 mol), 26.8 g sodium hydroxide (0.67 mol), 99.17 g 3-chloro-2,4-pentanedione (0.74 mol), and 500 g water were added to a reaction flask, heated to 50° C., and stirred for reaction for 6 h. TLC detection of the reaction liquid showed that xylose had basically disappeared, and the reaction was completed. The temperature was lowered, and a brown-yellow solid was precipitated. The solid was filtered and dried in a vacuum to obtain 135.46 g of intermediate A with a yield of about 90.0% and a purity of 98.5%.

[0075] The intermediate A obtained above was added into an autoclave, and 6.77 g of platinum / carbon catalyst and 550 ml of methanol were added. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times, and replaced with hydrogen three times, and the pressure was increased to 4 MPa. The airtightness of the reactor was checked, and the reactor was stirred, and the temperature was raised to 60°C, and the hydrogen pressure in the reactor was maintained at 4 MPa. The reaction was carried out for 4 hours, and the heating was turned off. The reactor was cooled to room temperature, and the gas in the autoclave was slowly discharged. The stirring was stopped, and the catalyst in the system was filtered out. The reaction was concentrated under reduced pressure to obtain 91.87 g of a colorless to light yellow oil, i.e., the target product, boson, with a yield of about 80.1% and a purity of 98.2%.

[0076] Embodiment 3:

[0077] 100.00g D-xylose (0.67mol), 92.6g potassium carbonate (0.67mol), 99.17g 3-chloro-2,4-pentanedione (0.74mol), 500g water were added to the reaction bottle, heated to 50°C, stirred and reacted for 4h, and the reaction liquid was tested by TLC. Xylose was almost gone, and the reaction was completed. The temperature was lowered, and a brown-yellow solid was precipitated. It was filtered and dried in vacuum to obtain 127g of intermediate A, with a yield of about 84.4% and a purity of 98.0%.

[0078] The intermediate A obtained above was added into an autoclave, and 6.35 g of Raney nickel catalyst and 550 ml of methanol were added. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times, and then replaced with hydrogen three times, and the pressure was increased to 4 MPa. The airtightness of the reactor was checked to be good, and the reaction was stirred. The temperature was raised to 40°C, and the hydrogen pressure in the autoclave was maintained at 4 MPa. The reaction was carried out for 4 hours, and the heating was turned off. The autoclave was cooled to room temperature, and the gas in the autoclave was slowly discharged. The stirring was stopped, and the catalyst in the system was filtered out. The reaction was concentrated under reduced pressure to obtain 88.71 g of a nearly colorless to light yellow oil, i.e., the target product boson, with a yield of 82.5% and a purity of 98.1%.

[0079] Example 4: 100.00 g D-xylose (0.67 mol), 37.6 g potassium hydroxide (0.67 mol), 99.17 g 3-chloro-2,4-pentanedione (0.74 mol), and 500 g water were added to a reaction flask, heated to 40°C, stirred and reacted for 4 h, and the reaction liquid was tested by TLC. Xylose was basically gone, and the reaction was completed. The temperature was lowered, and a brown-yellow solid was precipitated. It was filtered and vacuum dried to obtain 130 g of intermediate A, with a yield of about 86.4% and a purity of 98.4%.

[0080] The intermediate A obtained above was added into an autoclave, and 13.0 g of palladium / carbon catalyst and 550 ml of methanol were added. The autoclave was closed, and the air in the autoclave was replaced with nitrogen three times, and then replaced with hydrogen three times, and the pressure was increased to 2 MPa. The airtightness of the reactor was checked, and the mixture was stirred. The temperature was raised to 40°C, and the hydrogen pressure in the reactor was maintained at 2 MPa. The reaction was carried out for 6 hours, and the heating was turned off. The mixture was cooled to room temperature, and the gas in the autoclave was slowly discharged. The stirring was stopped, and the catalyst in the system was filtered out. The reaction was concentrated under reduced pressure to obtain 92.7 g of a colorless to light yellow oil, i.e., the target product, boson, with a yield of about 84.2% and a purity of 98.4%.

Claims

1. A method for synthesizing boson, characterized in that: The steps include: (1) Under the condition of alkaline compounds as catalysts, D-xylose and 3-halogenated-2,4-pentanedione are used as reaction materials, and the reaction is carried out at 30-90°C for 2-8 hours to synthesize intermediate A; (2) The intermediate A obtained in step (1) is reduced by catalytic hydrogenation in the presence of a catalyst to obtain the target compound hydroxypropyl tetrahydropyrantriol; wherein X is selected from Cl, Br, I; In step (1), the catalyst is one or more of sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide; In step (1), the molar ratio of D-xylose to 3-halogenated-2,4-pentanedione is 1:1-2; In step (2), the catalyst is one or more of Raney nickel, palladium / carbon, and platinum / carbon; In step (2), the mass ratio of intermediate A to catalyst is: 1:1%~20%; In step (2), the reaction temperature is 40-60°C and the reaction time is 4-6 h.

2. The method for synthesizing boson according to claim 1, characterized in that: In step (1), the molar ratio of D-xylose to 3-halogenated-2,4-pentanedione is 1:1.1-1.

3.

3. The method for synthesizing boson according to claim 1, characterized in that: In step (1), the reaction temperature is 30-50°C and the reaction time is 4-8h.

4. The method for synthesizing boson according to claim 1, characterized in that: In step (2), the mass ratio of intermediate A to catalyst is 1:3% to 10%.

5. Use of the synthesis method according to any one of claims 1 to 4 in the preparation of boson.

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