Preparation method of low-boron low-salt configuration proportion-controllable glassine

Abstract

The invention relates to a preparation method of a low-boron low-salt configuration proportion-controllable glassine, and relates to the technical field of chemical synthesis. The method provided by the invention is a production method for preparing colorless, odorless, low-salt and low-borate-residue glass pigment which is easy to amplify, low in three wastes and low in cost in a large scale, and the configuration proportion of the glass pigment is easy to control. The method not only solves the technical problems of high boron-containing inorganic matter content and high salt content of glass color in the prior art, but also achieves the technical effects of cheap and easily available reaction raw materials, high purity, efficient reaction and few three wastes.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical synthesis, and in particular to a method for producing colorless, odorless, low-salt, low-boron and metal-residue-free bosonine. Background Art

[0002] Pro-Xylane is the brand name of the cosmetic raw material independently developed by L'Oreal Group. Its specific components are hydroxypropyl tetrahydropyrantriol solution (the remaining components are water and alcohol compounds for preservation. The most common specification is 30% concentration solution). The effective active substance is hydroxypropyl tetrahydropyrantriol. Pro-Xylane can effectively promote collagen synthesis, resist skin aging, and improve skin fine lines. At present, the domestic cosmetic raw material industry refers to hydroxypropyl tetrahydropyrantriol as Pro-Xylane.

[0003] At present, there are many related patents and literatures on the preparation methods of bosine, but most of the domestic processes use alkaline metal reduction and hydrogenation reduction, which have some problems: 1. During the production process, reduction by alkaline metal compounds will lead to the production of a large amount of salts that are difficult to remove. 2. The use of metal catalysts for hydrogenation reduction will result in heavy metal residues in the product. 3. Most preparation methods are difficult to control the isomer ratio.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] In view of the technical problems existing in the prior art, the present invention provides a method for producing boson. The present invention provides a method for preparing colorless, odorless, metal-free and low-borate boson in large quantities, which is easy to scale up, has low three wastes and low cost, and can provide boson products with any isomer ratio.

[0006] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0007] The synthetic route of the present invention is as follows:

[0008]

[0009] A method for preparing boson, the method comprising the following steps:

[0010] (1) Using D-xylose and acetylacetone as raw materials and an inorganic base as a catalyst to prepare intermediate 2;

[0011] (2) reacting intermediate 2 with acetic anhydride in the presence of triethylamine to obtain intermediate 3;

[0012] (3) removing the acetyl group from intermediate 3 under base catalysis, and recrystallizing the crude product to obtain intermediate 4;

[0013] (4) subjecting the intermediate 4 to a reduction reaction with sodium borohydride in a reaction solvent in the presence of an acid to obtain hydroxypropyl tetrahydropyrantriol; filtering the reaction solution to remove salt, replacing the solvent with water to obtain an aqueous solution of hydroxypropyl tetrahydropyrantriol, and subjecting the aqueous solution of hydroxypropyl tetrahydropyrantriol to ion exchange with an ion exchange resin to obtain a bosquine solution.

[0014] The preparation method of bosogen of the present invention may further include:

[0015] (5) The solvent of the aqueous solution of bosine is replaced with alcohol, the temperature is lowered to -5 to 5°C, a solid is precipitated, and bosine is obtained.

[0016] Furthermore, in step (1), the molar ratio of D-xylose, acetylacetone and inorganic base is 1:1.1-2.5:1.1-2.5, preferably 1:1.2-2.0:1.2-2.0.

[0017] Furthermore, in step (1), the inorganic base is selected from at least one of hydroxide, carbonate and bicarbonate; preferably, the inorganic base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate and potassium bicarbonate.

[0018] Furthermore, in step (1), the reaction solvent is selected from at least one of an alcohol solvent, an ether solvent, an ester solvent, and a halogenated hydrocarbon; preferably, the reaction solvent is selected from at least one of methanol, ethanol, ether, tetrahydrofuran, ethyl acetate, dichloromethane, and chloroform.

[0019] Furthermore, in step (1), the reaction temperature is 20 to 60° C., preferably 30 to 50° C.; the reaction time is 1 to 8 hours, preferably 1 to 4 hours.

[0020] Furthermore, in step (1), after the reaction, the pH of the solution is adjusted to 7 to 8. Preferably, the pH of the solution is adjusted to 7 to 8 using an acid such as glacial acetic acid, hydrochloric acid, or sulfuric acid.

[0021] Furthermore, in step (1), D-xylose and acetylacetone are added to a reaction solvent at 15-25°C, an inorganic base is added, and the reaction is stirred at 20-60°C; after the reaction is completed, the pH is adjusted to 7-8, and the solvent in the organic phase is removed under reduced pressure to obtain intermediate 2.

[0022] Furthermore, in step (2), the molar ratio of intermediate 2, triethylamine and acetic anhydride is 1:2-6:2-6, preferably 1:3-5:3-5.

[0023] Furthermore, 4-dimethylaminopyridine can be added in step (2); the molar ratio of the intermediate 2 to 4-dimethylaminopyridine is 1:0.01-0.1, preferably 1:0.03-0.06.

[0024] Furthermore, in step (2), the reaction solvent is selected from at least one of ether solvents, ester solvents, and halogenated hydrocarbons; preferably, the reaction solvent is selected from at least one of diethyl ether, ethyl acetate, dichloromethane, and chloroform.

[0025] Furthermore, in step (2), the reaction temperature is 20 to 50° C., preferably room temperature; and the reaction time is 1 to 12 hours, preferably 2 to 8 hours.

[0026] Furthermore, in step (2), after the reaction is completed, the organic phase is washed with purified water to remove salt and triethylamine.

[0027] Furthermore, in step (2), intermediate 2, triethylamine and optional 4-dimethylaminopyridine are added to the reaction solvent, the temperature is controlled at 0-10°C, acetic anhydride is slowly added dropwise, and after reacting at 20-50°C for 1-12 hours, the organic phase is washed with purified water, and the organic phase is concentrated to obtain intermediate 3.

[0028] Furthermore, in step (3), the molar ratio of intermediate 3 to base is 1:0.005-0.05, preferably 1:0.01-0.02.

[0029] Furthermore, in step (3), the base is selected from at least one of hydroxides, carbonates, and bicarbonates; preferably, the base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, and potassium bicarbonate.

[0030] Furthermore, in step (3), the reaction solvent is selected from at least one of an alcohol solvent, an ether solvent, an ester solvent, and a halogenated hydrocarbon; preferably, the reaction solvent is selected from at least one of methanol, ethanol, ether, tetrahydrofuran, ethyl acetate, dichloromethane, and chloroform.

[0031] Furthermore, in step (3), the reaction temperature is 20 to 60° C., preferably room temperature; and the reaction time is 1 to 8 hours, preferably 1 to 6 hours.

[0032] Furthermore, in step (3), the solvent used for recrystallization is selected from commonly used crystallization solvents for saccharide compounds, such as methanol, ethanol, and isopropanol.

[0033] Furthermore, in step (3), intermediate 3 is added to a reaction solvent, a base is added, and the mixture is reacted at 20 to 60° C. for 1 to 8 hours. The organic phase is concentrated and recrystallized to obtain intermediate 4.

[0034] Further, in step (4), the molar ratio of intermediate 4, acid, and sodium borohydride is 1:0.1 to 1:0.3 to 0.8. Preferably, the molar ratio of intermediate 4 to acid is 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0; the molar ratio of intermediate 4 to sodium borohydride is 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8. Therefore, the molar ratio of intermediate 4, acid, and sodium borohydride is preferably 1:0.2 to 1.0:0.4 to 0.6.

[0035] Furthermore, in step (4), the reaction solvent is selected from water, methanol, ethanol, and isopropanol.

[0036] Furthermore, in step (4), the ratio of intermediate 4 to reaction solvent is 1 mol: 500-3000 ml, preferably 1 mol: 800-1200 ml.

[0037] Furthermore, in step (4), the acid includes organic acid and inorganic acid. The organic acid includes acetic acid and oxalic acid. The inorganic acid includes hydrochloric acid and sulfuric acid.

[0038] Furthermore, in step (4), the reaction temperature is -10 to 60°C, preferably 0 to 30°C, and more preferably room temperature. The reaction temperature has a certain influence on the product configuration ratio, and the product configuration ratio can be accurately controlled within 5% of the ratio under room temperature.

[0039] Furthermore, in step (4), the reaction time is 1 to 10 hours, preferably 1 to 6 hours.

[0040] Furthermore, in step (4), the ion exchange resin includes an anion exchange resin, a cation exchange resin, an ion exchange resin for boron removal and optionally a metal ion exchange resin.

[0041] Furthermore, in step (5), the alcohol is selected from methanol, ethanol and isopropanol.

[0042] Furthermore, in step (5), the temperature is lowered to 0°C.

[0043] Furthermore, in the present invention, the ratio of S and R configurations at the β position in the Bose-containing product (including Bose-containing solution and solid Bose-containing) can be adjusted at will, wherein the ratio of the S configuration can be 30% to 100%, for example, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, 100%.

[0044] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0045] 1. The present invention provides a method of intervening the chiral selection in the reaction process by adding a small amount of acid to the sodium borohydride reduction reaction system for catalysis, and accurately controlling the ratio of bosones with different configurations, which effectively solves the problem of too low effective configuration components of bosones in the prior art. In addition, by changing the temperature of the reaction system, the ratio of the product configuration can be accurately controlled to be adjusted within 5% of the original ratio.

[0046] 2. The present invention also provides a method for effectively reducing the salt content of the boson product, firstly removing most of the salt by filtration, and then using ion exchange resin to remove ppm level residues, which effectively solves the problem of difficulty in removing impurities in the boson product in the prior art.

[0047] 3. The preparation method of the present invention has simple process, readily available raw materials, low cost, easy purification of intermediate products and final products, high yield and purity, and is very suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 : The relationship between Bose configuration and the amount of acid added. DETAILED DESCRIPTION

[0049] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0050] The experimental methods in the following examples are conventional methods unless otherwise specified. If no specific techniques or conditions are specified in the examples, they are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0051] Example 1

[0052] A method for preparing low-salt and low-boron bosonine comprises the following steps:

[0053] Step 1: Preparation of Intermediate 1

[0054] At 15-25°C, D-xylose (15 g, 0.1 mol, 1.0 eq.) and acetylacetone (12 g, 0.12 mol, 1.2 eq.) were added to a reaction bottle containing methanol (45 ml), and a sodium hydroxide aqueous solution (10%, 75 ml, 1.5 eq.) was added dropwise. After the addition was completed, the system was heated to 35°C and stirred for reaction for 2 hours, and the reaction was completed;

[0055] After the reaction was completed, glacial acetic acid (2.4 g, 0.04 mol, 0.4 eq.) was added to adjust the pH to 7, and the solvent in the organic phase was removed under reduced pressure to obtain intermediate 2 (19 g) for standby use;

[0056] Step 2: Preparation of Intermediate 2

[0057] Dichloromethane (40 ml) was added to the reactor, and then intermediate 2 (19 g, 0.1 mol, 1.0 eq.), triethylamine (40.4 g, 0.4 mol, 4 eq.) and DMAP (0.6 g, 0.005 mol, 0.05 eq.) were added to the above solution, and acetic anhydride (46 g, 0.4 mol, 4 eq.) was added dropwise at a temperature of 0-10° C., and stirred at room temperature for 6 hours. The organic phase was washed with purified water to remove salt and triethylamine, and the organic phase was concentrated to obtain intermediate 3 (12.9 g).

[0058] Step 3: Preparation of Intermediate 3

[0059] Intermediate 3 (12.9 g, 0.04 mol, 1 eq.) was added to methanol (65 ml), and sodium carbonate (39 mg, 0.01 eq.) was added. After stirring at room temperature for 2 hours, the organic phase was concentrated and the solvent was replaced with ethanol. The temperature was raised to 50°C and stirred until the product was completely dissolved. The temperature was lowered for crystallization and filtered to obtain a light yellow solid intermediate 4 (7.8 g, more than 99% of the single configuration at the α position).

[0060] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0061] The intermediate 4 (7.8 g, 0.04 mol, 1 eq.) was added to an ethanol solution (39 ml), and glacial acetic acid (0.74 g, 0.01 mol, 0.3 eq.) and sodium borohydride (0.78 g, 0.02 mol, 0.5 eq.) were added. After stirring at room temperature for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride, and most of the salt was removed by filtration. The solution was concentrated, and the solvent was replaced with purified water. An anion exchange resin (Purolite A103SPlus), a cation exchange resin (Mingzhu brand T211), and an ion exchange resin for boron removal (Purolite S108) were used to exchange and remove the residual sodium salt and borate and other inorganic substances in the system to obtain a colorless, odorless, metal-free, low-salt and low-boron boson solution (30% aqueous solution, 23 g, σ≤30 μS / cm, β-position configuration ratio S: R=60:40).

[0062] 1H NMR (600MHz, Deuterium Oxide) δ4.00 (q, J=6.4Hz, 1H), 3.90 (dd, J=11.3, 5.5Hz, 1H), 3.55 (td, J=10.0, 5.4Hz, 1H), 3.36 (t, J=9.1Hz, 1H), 3.30 (td, J=9. 7, 2.6Hz, 1H), 3.22 (t, J=11.0Hz, 1H), 3.15 (t, J=9.3Hz, 1H), 1.94-1.85 (m, 1H), 1.62 (ddd, J=14.7, 9.6, 5.9Hz, 1H), 1.16 (d, 3H).

[0063] Example 2

[0064] Step 3: Preparation of Intermediate 3

[0065] Intermediate 3 (15 g, 0.05 mol, 1 eq.) was added to methanol (75 ml), and potassium carbonate (65 mg, 0.01 eq.) was added. After stirring at room temperature for 2 hours, the mixture was filtered and concentrated. The organic phase was concentrated and the solvent was replaced with ethanol. The mixture was heated to 50°C and stirred until the product was completely dissolved. The temperature was lowered for crystallization and the light yellow solid intermediate 4 (11 g, more than 99% single configuration) was obtained by filtration.

[0066] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0067] The intermediate 4 (10 g, 0.05 mol, 1 eq.) was added to water (50 ml), and glacial acetic acid (0.5 g, 0.006 mol, 0.2 eq.) and sodium borohydride (1 g, 0.025 mol, 0.4 eq.) were added. After stirring at room temperature for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride, and most of the salt was removed by filtration. The solution was concentrated, and the solvent was replaced with purified water. An anion exchange resin (Purolite A103SPlus), a cation exchange resin (Mingzhu brand T211), and an ion exchange resin for boron removal (Purolite S108) were used to exchange and remove the residual sodium salt and borate and other inorganic substances in the system to obtain a colorless, odorless, metal-free, low-salt and low-boron boson solution (30% aqueous solution, 33 g, σ≤30 μS / cm, β-position configuration ratio S: R=46:54).

[0068] Example 3

[0069] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0070] The intermediate 4 (10 g, 0.05 mol, 1 eq.) was added to methanol (50 ml), and glacial acetic acid (0.5 g, 0.006 mol, 0.2 eq.) and sodium borohydride (1 g, 0.025 mol, 0.5 eq.) were added. After stirring at room temperature for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride, and most of the salt was removed by filtration. The mixture was concentrated, and the solvent was replaced with purified water. An anion exchange resin (Purolite A103SPlus), a cation exchange resin (Mingzhu brand T211), and an ion exchange resin for boron removal (Purolite S108) were used to remove the residual sodium salt and borate and other inorganic substances in the system to obtain a colorless, odorless, metal-free, low-salt, low-boron boson solution (30% aqueous solution, 33 g, σ≤30 μS / cm, β-position configuration ratio S: R=35:65).

[0071] Example 4

[0072] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0073] The intermediate 4 (10 g, 0.05 mol, 1 eq.) was added to ethanol (50 ml), and dilute hydrochloric acid (0.5 g, 0.006 mol, 0.2 eq.) and sodium borohydride (1 g, 0.025 mol, 0.5 eq.) were added. After stirring at room temperature for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride, and most of the salt was removed by filtration. The mixture was concentrated, and the solvent was replaced with purified water. An anion exchange resin (Purolite A103SPlus), a cation exchange resin (Mingzhu brand T211), and an ion exchange resin for boron removal (Purolite S108) were used to exchange and remove the residual sodium salt and borate and other inorganic substances in the system to obtain a colorless, odorless, metal-free, low-salt and low-boron boson solution (30% aqueous solution, 33 g, σ≤30 μS / cm, β-position configuration ratio S: R=57:43).

[0074] Example 5

[0075] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0076] The intermediate 4 (10 g, 0.05 mol, 1 eq.) was added to ethanol (50 ml), and dilute hydrochloric acid (0.5 g, 0.006 mol, 0.2 eq.) was added. After cooling to 0°C, sodium borohydride (1 g, 0.025 mol, 0.5 eq.) was added under temperature-controlled conditions. After stirring at 0°C for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride. Most of the salt was removed by filtration, and the mixture was concentrated. The solvent was replaced with purified water, and the residual sodium salt and borate and other inorganic substances in the system were removed by anion exchange resin (Purolite A103SPlus), cation exchange resin (Mingzhu brand T211), and ion exchange resin for boron removal (Purolite S108) to obtain a colorless, odorless, metal-free, low-salt, low-boron boson solution (30% aqueous solution, 32.7 g, σ≤30 μS / cm, β-position configuration ratio S: R=59:41).

[0077] Example 6

[0078] Step 4: Preparation of Hydroxypropyl Tetrahydropyrantriol

[0079] The intermediate 4 (10 g, 0.05 mol, 1 eq.) was added to isopropanol (50 ml), and glacial acetic acid (1.5 g, 0.02 mol, 0.6 eq.) and sodium borohydride (2 g, 0.05 mol, 1 eq.) were added. After stirring at room temperature for 2 hours, dilute hydrochloric acid was added dropwise to quench the sodium borohydride, and the mixture was filtered and concentrated. The solvent was replaced with purified water, and an anion exchange resin (Purolite A103SPlus), a cation exchange resin (Mingzhu brand T211), and an ion exchange resin for boron removal (Purolite S108) were used to exchange and remove inorganic substances such as residual sodium salt and borate in the system. The solvent was replaced with ethanol, and the temperature was lowered to 0°C and stirred for 6 hours to precipitate a solid. The solid was filtered and dried to obtain a colorless, odorless, metal-free, low-salt, low-boron white solid of boron (8.7 g, σ≤30 μS / cm (based on 30% aqueous solution), β-position configuration ratio S:R=99.3:0.7).

[0080] Referring to Example 2, the amount of solvent and glacial acetic acid added in the fourth step was adjusted, and the configuration ratio of Bose-containing protein obtained under different conditions was measured. The results are as follows: Figure 1 The horizontal axis of the figure is the corresponding molar equivalent of glacial acetic acid added, and the vertical axis is the S configuration ratio.

[0081] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing boson, the method comprising the following steps: (1) Using D-xylose and acetylacetone as raw materials and an inorganic base as a catalyst to prepare intermediate 2; (2) reacting intermediate 2 with acetic anhydride in the presence of triethylamine to obtain intermediate 3; (3) removing the acetyl group from intermediate 3 under base catalysis, and recrystallizing the crude product to obtain intermediate 4; (4) subjecting the intermediate 4 to a reduction reaction with sodium borohydride in a reaction solvent in the presence of an acid to obtain hydroxypropyl tetrahydropyrantriol; filtering the reaction solution to remove salt, replacing the solvent with water to obtain an aqueous solution of hydroxypropyl tetrahydropyrantriol, and subjecting the aqueous solution of hydroxypropyl tetrahydropyrantriol to ion exchange with an ion exchange resin to obtain a bosquine solution.

2. The preparation method according to claim 1, characterized in that: The preparation method further comprises: (5) The solvent of the aqueous solution of bosine is replaced with alcohol, the temperature is lowered to -5 to 5°C, a solid is precipitated, and bosine is obtained.

3. The preparation method according to claim 1, characterized in that: In step (2), the molar ratio of intermediate 2, triethylamine and acetic anhydride is 1:2-6:2-6, preferably 1:3-5:3-5.

4. The preparation method according to claim 1, characterized in that: 4-Dimethylaminopyridine can also be added in step (2); the molar ratio of the intermediate 2 to 4-dimethylaminopyridine is 1:0.01-0.1, preferably 1:0.03-0.

06.

5. The preparation method according to claim 1, characterized in that: In step (2), intermediate 2, triethylamine and optional 4-dimethylaminopyridine are added to the reaction solvent, the temperature is controlled at 0-10°C, acetic anhydride is slowly added dropwise, and after reacting at 20-50°C for 1-12 hours, the organic phase is washed with purified water and concentrated to obtain intermediate 3.

6. The preparation method according to claim 1, characterized in that: In step (3), the molar ratio of intermediate 3 to base is 1:0.005-0.05, preferably 1:0.01-0.02; the base is selected from at least one of hydroxide, carbonate, and bicarbonate; preferably, the base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, and potassium bicarbonate.

7. The preparation method according to claim 1, characterized in that: In step (4), the molar ratio of intermediate 4, acid and sodium borohydride is 1:0.1 to 1:0.3 to 0.8, preferably 1:0.2 to 1.0:0.4 to 0.

6.

8. The preparation method according to claim 1, characterized in that: In step (4), the reaction solvent is selected from water, methanol, ethanol, and isopropanol; the acid includes organic acids and inorganic acids; the organic acid includes acetic acid and oxalic acid; the inorganic acid includes hydrochloric acid and sulfuric acid.

9. The preparation method according to claim 1, characterized in that: In step (4), the reaction temperature is -10 to 60°C, preferably -0 to 30°C.

10. The preparation method according to claim 1, characterized in that: The ratio of the S and R configurations at the β position in the Bose product can be adjusted at will, wherein the ratio of the S configuration can be 30% to 100%.

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