A method for preparing boson

Abstract

The invention belongs to the field of organic synthesis, fine chemicals and daily chemicals, and specifically relates to a method for preparing bosine from xylose and acetylacetone in one pot. The method is simple to operate, the reagents are cheap and readily available, and has good industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, fine chemicals and daily chemicals, and particularly relates to a method for preparing bosogenin by a one-pot process. Technical Background

[0002] Pro-Xylane is a xylose derivative commonly found in cosmetics, also known as hydroxypropyl tetrahydropyrantriol (CAS No. 439685-79-7). This bioactive substance was first derived from natural xylose by the L'Oreal Lancome laboratory. Pro-Xylane can directly affect the extracellular matrix in the three-layer structure of the skin, promote the synthesis of glycosaminoglycans in the skin, affect the secretion of glycosaminoglycans, thereby improving the adhesion between the epidermis and the dermis, promoting the regeneration of damaged skin tissue, and helping to maintain the elasticity of the dermis. The mechanism of action of Pro-Xylane is mainly reflected in stimulating the synthesis of glycosaminoglycans GAGs, promoting the production of hyaluronic acid and collagen, preventing skin aging, and effectively keeping the skin firm and delicate, delaying skin aging.

[0003] The commonly used synthetic routes are:

[0004]

[0005] At present, the chemical preparation of pro-Xylane mostly adopts a two-step method. For example, Cavezza et al. used xylose as the raw material. In the first step, it reacted with acetylacetone in the presence of a strong inorganic base for 12 hours, and then used a strong acidic cation exchange resin for acidification to obtain β-acetone xyloside; in the second step, NaBH4 was used to reduce the carbonyl group for 12 hours to successfully obtain pro-Xylane [Synthesis of Pro-Xylane TM: a new biologically active C-glycoside in aqueous media. Bioorg Med Chem Lett, 2009, 19 (3): 845-849]; this reaction is regarded as one of the successful cases of green chemical synthesis of pro-Xylane. Using metal hydrides such as NaBH4 or LiAlH4 to reduce β-acetone xyloside to synthesize pro-Xylane is a commonly used method in the second step of the two-step method. This has the problem that the subsequent process uses ion exchange resin for desalination, and the amount of wastewater for ion resin regeneration is very large. The wastewater must be treated when the production is scaled up, which is costly and pollutes the environment.

[0006] The invention patent CN 113735811 A discloses a method for synthesizing bosonine by acylation protection and then reduction. The method is divided into three steps: (1) acetylacetone or acetoacetate ester compound, xylose and alkaline substance are mixed in a solvent and heated to react to obtain a first intermediate product, β-acetone xyloside; (2) the β-acetone xyloside is acylated with an acylating agent to obtain a second intermediate product in which all hydroxyl groups are protected by acyl groups; (3) the second intermediate product is reduced with a reducing agent (one or more of lithium aluminum hydride, diisobutyl aluminum hydride and red aluminum) in a solvent to obtain bosonine; wherein the heating reaction time for synthesizing the first intermediate product, β-acetone xyloside, is 10-16 hours, preferably 12-14 hours; the acylation reaction time for synthesizing the second intermediate product is 20-30 hours; and the reduction reaction time is preferably 10-14 hours. It can be seen that the three-step synthesis method has the problems of many steps, long time and low production efficiency.

[0007] Patent CN 113773291 A discloses an improved method for synthesizing bosonine, which comprises dissolving β-acetone xyloside and triphenylboron (BPh3) in isopropanol and then preheating the mixture to 60-70°C; simultaneously filling a palladium carbon catalyst into a reactor, opening a hydrogen feed valve and a nitrogen feed valve, controlling the flow rate, and then adding the preheated raw material solution to a reaction module to perform a gas-liquid-solid three-phase reaction, followed by post-treatment to obtain the target product bosonine; the BPh3 used in the present invention is expensive, and the investment in the fully automatic hydrogenation reactor equipment is high. Summary of the invention

[0008] The technical task of the present invention is to make up for the deficiencies of the prior art and provide a method for preparing boson, which is a one-pot chemical synthesis, has low raw material cost, simple preparation process, easy operation, low reaction energy consumption, and has industrial application prospects.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] D-xylose, acetylacetone, a solid inorganic base and isopropanol are mixed, and the mixture is placed in a variable frequency microwave synthesizer. When the mixture is heated to 45-50° C., the mixture is kept warm and stirred for 5-10 minutes. The temperature is further raised to 70-76° C., a nano nickel catalyst is added, and the mixture is stirred and reacted for 10-15 minutes. The heating is stopped, the mixture is cooled to room temperature, and the catalyst is removed by centrifugation. The obtained liquid is rotary evaporated in a water bath to obtain a light yellow crude product of bosquine. The crude product is purified by column chromatography (silica gel, n-hexane / ethyl acetate) to obtain a bosquine product with a yield of 82-85%.

[0011] The solid inorganic base is NaOH and KOH;

[0012] The molar ratio of D-xylose, acetylacetone and inorganic base is 1:1.2-1.5:2.0-2.3;

[0013] The amount of isopropanol used is 6-7 times the mass of xylose;

[0014] The variable frequency microwave synthesizer has a power of 0-1000W;

[0015] The nano nickel catalyst is used in an amount of 0.3-0.5% of the mass of xylose;

[0016] The nano nickel catalyst is prepared in the following steps:

[0017] Nickel acetylacetonate (5 mmol) and oleylamine (100 mL) were mixed evenly, transferred to a stainless steel autoclave, sealed and heated to 220°C, kept warm for 1 hour, cooled naturally to room temperature, centrifuged, and the obtained solid was washed with n-hexane and ethanol for 3 times respectively, and vacuum dried at 80°C for 4 hours to obtain a nano nickel catalyst;

[0018] The size of the nano nickel catalyst is about 100 nm.

[0019] Beneficial technical effects of the present invention:

[0020] (1) The preparation method of bosonine of the present invention is a one-pot synthesis, which eliminates the need for complex post-processing processes such as separation of intermediate products; the cost of the raw materials used is low, the preparation time is short, the process is simple, the conditions are mild, the operation is easy, the reaction energy consumption is low, and it has industrial application prospects.

[0021] (2) The preparation method of bosogenin of the present invention directly uses solid NaOH or KOH to catalyze xylose to prepare β-acetone xyloside, abandoning the method of catalysis by NaOH, KOH or NaHCO3 aqueous solution. The use of this raw material significantly simplifies the post-treatment process.

[0022] (3) As a high-frequency electromagnetic wave, microwaves can promote many chemical reactions. They have the advantages of simple operation, low synthetic energy consumption, short reaction time, less reaction, easy purification, high yield, and environmental friendliness. Microwaves can shorten many reaction times from hours to minutes. With the development of society, environmentally friendly green chemical preparation will become the goal pursued by chemists. This method uses microwave synthesis and combines nano-nickel catalysts to reduce the synthesis time of the intermediate product β-acetone xyloside to 5-10 minutes; the synthesis time of isopropanol reduction of β-acetone xyloside to bosylamine is 10-15 minutes. It can be seen that the reaction efficiency is significantly improved.

[0023] (4) The preparation method of bosogen of the present invention uses a nano-nickel catalyst and combines microwave radiation to successfully achieve a short time and high efficiency reduction of β-acetone xyloside to bosogen using isopropanol as a hydrogen source. This method avoids the complicated process of introducing an inorganic reducing agent NaBH4 or LiAIH4 as a hydrogen source to reduce the carbonyl group to the hydroxyl group. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The accompanying drawings are used to provide a further understanding of the present invention, and the embodiments of the present invention and their descriptions are used to explain the present invention, and do not constitute improper limitations on the present invention.

[0025] Figure 1 This is the XRD pattern of the nano-nickel catalyst synthesized in Example 1.

[0026] Figure 2 SEM morphology of the nano-nickel catalyst synthesized in Example 1

[0027] Figure 3 This is the TEM morphology of the nano-nickel catalyst synthesized in Example 1. DETAILED DESCRIPTION

[0028] The present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to the embodiments, and all changes made to the technical solution of the present invention by professionals in the field should fall within the protection scope of the present invention.

[0029] Example 1 Preparation method of nano nickel catalyst

[0030] Nickel acetylacetonate (5 mmol) and oleylamine (100 mL) were mixed evenly, transferred to a stainless steel autoclave, sealed and heated to 220°C, kept warm for 1 hour, cooled naturally to room temperature, centrifuged, and the obtained solid was washed with n-hexane and ethanol for 3 times respectively, and vacuum dried at 80°C for 4 hours to obtain a nano nickel catalyst;

[0031] The nano-nickel catalyst was characterized by XRD patterns. Figure 1 As shown in the figure, three obvious diffraction peaks appeared at 2θ values ​​of 44.5°, 51.8°, and 76.4°, corresponding to the (111), (200), and (220) crystal planes of the nickel metal face-centered cubic phase, which is consistent with the standard PDF database (JCPDS card number 04-0850), indicating that nano-nickel was successfully synthesized under the current conditions; the diffraction peak of the sample is sharp and narrow, indicating that it has a good crystal structure; Figure 2 shows the SEM image of the obtained nickel catalyst, indicating that the product consists of nanoparticles with a size of approximately 100 nm; Figure 3 The transmission electron microscopy (TEM) images further confirmed the morphology of the nano-nickel catalyst.

[0032] Example 2 A method for preparing boson

[0033] D-xylose, acetylacetone, solid inorganic base and isopropanol are mixed, and the mixture is placed in a variable frequency microwave synthesizer, heated to 45°C, and stirred for 10 minutes; the temperature is further raised to 70°C, a nano nickel catalyst is added, and the reaction is stirred for 15 minutes, the heating is stopped, the mixture is cooled to room temperature, and the catalyst is removed by centrifugation, and the obtained liquid is evaporated in a water bath to obtain a light yellow phosgene crude product, and the crude product is purified by column chromatography (silica gel, n-hexane / ethyl acetate) to obtain a phosgene product with a yield of 82%;

[0034] The solid inorganic base is NaOH;

[0035] The amounts of D-xylose, acetylacetone and inorganic base are 0.1 mol, 0.12 mol and 0.2 mol respectively;

[0036] The isopropanol is used in an amount of 90 g;

[0037] The nano nickel catalyst is used in an amount of 4.5 g;

[0038] The power of the variable frequency microwave synthesizer is 0-1000W.

[0039] Example 3

[0040] D-xylose, acetylacetone, a solid inorganic base and isopropanol are mixed, and the mixture is placed in a variable frequency microwave synthesizer. When heated to 50° C., the mixture is stirred for 5 minutes; the temperature is further raised to 76° C., a nano nickel catalyst is added, and the reaction is stirred for 10 minutes. The heating is stopped, the mixture is cooled to room temperature, and the catalyst is removed by centrifugation. The obtained liquid is evaporated in a water bath to obtain a light yellow crude product of bosquine. The crude product is purified by column chromatography (silica gel, n-hexane / ethyl acetate) to obtain a bosquine product with a yield of 83%.

[0041] The solid inorganic base is KOH;

[0042] The amounts of D-xylose, acetylacetone and inorganic base are 0.1 mol, 1.5 mol and 2.3 mol respectively;

[0043] The isopropanol is used in an amount of 105 g;

[0044] The nano nickel catalyst is used in an amount of 7.5 g;

[0045] The power of the variable frequency microwave synthesizer is 0-1000W.

[0046] Example 4

[0047] D-xylose, acetylacetone, a solid inorganic base and isopropanol are mixed, and the mixture is placed in a variable frequency microwave synthesizer. When heated to 47°C, the mixture is kept warm and stirred for 7 minutes; the temperature is further raised to 73°C, a nano nickel catalyst is added, and the reaction is stirred for 13 minutes. The heating is stopped, the mixture is cooled to room temperature, and the catalyst is removed by centrifugation. The obtained liquid is evaporated in a water bath to obtain a light yellow crude product of bosquine. The crude product is purified by column chromatography (silica gel, n-hexane / ethyl acetate) to obtain a bosquine product with a yield of 83%.

[0048] The solid inorganic base is NaOH;

[0049] The molar ratio of D-xylose, acetylacetone and inorganic base is 0.1 mol, 0.135 mol and 2.15 mol;

[0050] The isopropanol is used in an amount of 97.5 g;

[0051] The variable frequency microwave synthesizer has a power of 0-1000W;

[0052] The amount of nano nickel catalyst used is 6 g.

[0053] The raw materials and reagents used in the following examples are all commercially available.

Claims

1. A method for preparing boson, characterized in that: The steps are as follows: D-xylose, acetylacetone, solid inorganic base and isopropanol are mixed, the mixture is placed in a variable frequency microwave synthesizer, heated to 45-50°C, and stirred for 5-10 minutes; the temperature is further increased to 70-76°C, a nano nickel catalyst is added, the reaction is stirred for 10-15 minutes, the heating is stopped, the mixture is cooled to room temperature, the catalyst is removed by centrifugation, the obtained liquid is subjected to water bath rotary evaporation to obtain a light yellow phosgene crude product, the crude product is purified by column chromatography on silica gel and n-hexane / ethyl acetate to obtain a phosgene product with a yield of 82-85%; The solid inorganic base is NaOH and KOH; The variable frequency microwave synthesizer has a power of 0-1000 W; The molar ratio of D-xylose, acetylacetone and inorganic base is 1:1.2-1.5:2.0-2.3; The amount of isopropanol used is 6-7 times the mass of D-xylose; The nano nickel catalyst is used in an amount of 0.3-0.5% of the mass of D-xylose; The size of the nano nickel catalyst is about 100 nm.

2. A method for preparing bosonine according to claim 1, characterized in that: The preparation steps of the nano nickel catalyst are as follows: nickel acetylacetonate and oleylamine are mixed evenly, transferred to a stainless steel autoclave, sealed and heated to 220°C, kept warm for 1 hour, naturally cooled to room temperature, centrifuged, and the obtained solid is washed with n-hexane and ethanol for 3 times respectively, and vacuum dried at 80°C for 4 hours to obtain a nano nickel catalyst; the nickel acetylacetonate is 5 mmol; the oleylamine is 100 mL.

Images