Preparation method of glycolaldehyde dimer

Abstract

The present application relates to a method for preparing glycolaldehyde dimer, which comprises the following steps: under the condition of the presence of a catalyst, subjecting glycolide to a hydrogenation reduction reaction to prepare the glycolaldehyde dimer; the catalyst is a supported catalyst, comprising a carrier and an active component supported on the carrier, and the active component is a ruthenium complex of β-cyclodextrin. This preparation method uses glycolide as a raw material, and under the condition of the presence of a catalyst supported with a ruthenium complex of β-cyclodextrin, prepares the glycolaldehyde dimer through a hydrogenation reduction reaction. The steps of this preparation method for preparing the glycolaldehyde dimer are simple, the cost is low, the post-treatment is simple, it is suitable for large-scale production, and has good industrial application value.

Description

Technical Field

[0001] This application relates to the technical field of compound synthesis, and particularly to a preparation method of glycolaldehyde dimer. Background Art

[0002] Glycolaldehyde dimer, also known as 1,4-dioxane-2,5-diol, can be used in the production of pesticides, photoresists, resins, coatings and dyes, and is also an important intermediate for a variety of drugs, such as anticancer targeted drugs, HIV protease inhibitors, antiviral drugs, etc. Marketed drugs such as Troxacitabine (English name: Troxacitabine, CAS: 145918-75-8), Lamivudine (English name: lamivudine, CAS: 134678-17-4), Emtricitabine (English name: Emtricitabine, CAS: 143491-57-0), Capecitabine (English name: Capecitabine, CAS: 154361-50-9), etc. all use glycolaldehyde dimer in their synthesis processes. Especially for Troxacitabine, it is an antitumor cytidine targeted drug developed by Yale University in the United States, which has significant curative effects on various cancers such as leukemia, lung cancer, liver cancer, prostate cancer, etc., and also has the characteristics of inhibiting hepatitis B virus and anti-hepatoma cells, and has important medicinal value and development prospects. There is a method to obtain various crystal forms of Troxacitabine, especially the crystal form stable at room temperature, through the configuration change using glycolaldehyde dimer as the raw material, which is convenient for the popularization and application of Troxacitabine.

[0003] However, most of the traditional synthesis methods of glycolaldehyde dimer have problems such as harsh reaction conditions, expensive raw materials, high cost, basically being produced in the form of by-products, and having no industrial application value. Summary of the Invention

[0004] Based on this, this application provides a preparation method of glycolaldehyde dimer, which has simple steps, low cost, simple post-treatment, and has good industrial application value.

[0005] In the first aspect of this application, a preparation method of glycolaldehyde dimer is provided, including the following steps:

[0006] Under the condition of the presence of a catalyst, perform a hydrogenation reduction reaction on glycolide to prepare the glycolaldehyde dimer;

[0007] The catalyst is a supported catalyst, including a carrier and an active component supported on the carrier, and the active component is a ruthenium complex of β-cyclodextrin.

[0008] In one embodiment, the glycolaldehyde dimer is cis-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a first solvent, which is one or more of alcohol solvents.

[0009] In one embodiment, the first solvent is one or more of alcohol solvents with a carbon chain length of C2-C10; further, the first solvent is one or more of isopropanol, isobutanol, isopentanol, isohexanol and isooctanol.

[0010] In one embodiment, the glycolaldehyde dimer is trans-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a second solvent, which is one or more of ketone solvents.

[0011] In one embodiment, the second solvent is one or more of ketone solvents with a carbon chain length of C2-C10; further, the second solvent is one or more of acetone, methyl ethyl ketone, butanone, pentanone, hexanone, octanone and cyclohexanone.

[0012] In one embodiment, the mass ratio of the glycolide to the first solvent or the second solvent is (20-100):100.

[0013] In one embodiment, the mass ratio of the catalyst to the glycolide is (2-10):100.

[0014] In one embodiment, the conditions of the hydrogenation reduction reaction include at least one of the following features (1)-(3):

[0015] (1) The reaction temperature is 100°C-150°C;

[0016] (2) The reaction time is 4 h-5 h;

[0017] (3) Hydrogen is introduced and the reaction pressure is maintained at 1.5 MPa-2.5 MPa.

[0018] In one embodiment, in the active component, the molar ratio of β-cyclodextrin to ruthenium is 1:(3-6).

[0019] In one embodiment, the carrier is a carbon-based material;

[0020] Further, the specific surface area of the carbon-based material is 800-1200 m 3 / g, and the total pore volume is 0.6-1.8 mL / g;

[0021] Further, the carbon-based material is one or more of activated carbon, carbon nanotubes and graphene.

[0022] In one embodiment, in the catalyst, the loading amount (wt%) of ruthenium is 8% to 12%.

[0023] In one embodiment, the preparation steps of the catalyst include:

[0024] Mix β-cyclodextrin, ruthenium chloride and water, and add a reducing agent under stirring to carry out a reduction reaction to prepare an active component solution;

[0025] Add a carrier to the active component solution, stir, filter and dry to prepare the catalyst.

[0026] In one embodiment, the reducing agent is one or more of sodium borohydride, potassium borohydride and lithium aluminum hydride.

[0027] In one embodiment, after the hydrogenation reduction reaction, a post-treatment step is further included:

[0028] Filter the reaction solution after the hydrogenation reduction reaction to remove the catalyst, cool the filtrate, collect the precipitated solid, and dry it to prepare the glycolaldehyde dimer.

[0029] The above preparation method uses glycolide as a raw material, and under the condition of the catalyst loaded with ruthenium complex of β-cyclodextrin, prepares glycolaldehyde dimer through a hydrogenation reduction reaction. The steps for preparing glycolaldehyde dimer by this preparation method are simple, the cost is low, and the post-treatment is simple, which is suitable for large-scale production and has good industrial application value. At the same time, the yield of glycolaldehyde dimer is relatively high.

[0030] In addition, glycolide is an intermediate of the biodegradable material polyglycolic acid (PGA), which is cheap, easy to obtain, and the preparation method is simple, feasible, green and environmentally friendly. Description of the Drawings

[0031] Figure 1 It is the total ion current chromatogram of GC-MS of the glycolaldehyde dimer prepared in Example 1;

[0032] Figure 2 It is the total ion current chromatogram of GC-MS of the glycolaldehyde dimer prepared in Example 2;

[0033] Figure 3 It is the total ion current chromatogram of GC-MS of the glycolaldehyde dimer prepared in Example 3. Detailed Embodiments

[0034] The following further elaborates on the preparation method of the glycolaldehyde dimer of the present application in combination with specific examples. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosed content of the present application more thorough and comprehensive.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this application belongs. The terms used in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0036] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0037] In this application, "the first aspect", "the second aspect", "the third aspect", "the fourth aspect", etc. are for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor should they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "the first", "the second", "the third", "the fourth", etc. are only for non-exhaustive enumeration and description purposes and should be understood not to constitute a closed limitation on quantity.

[0038] In this application, among the technical features described in an open-ended manner, it includes a closed technical solution composed of the listed features, as well as an open technical solution including the listed features.

[0039] In this application, regarding numerical ranges, unless otherwise specified, the above numerical ranges are considered continuous and include the minimum and maximum values of the range, as well as each value between such minimum and maximum values. Further, when the range refers to integers, it includes each integer between the minimum and maximum values of the range. In addition, when multiple ranges are provided to describe features or characteristics, these ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0040] Regarding the percentage content involved in this application, unless otherwise specified, for solid-liquid mixtures and solid-solid mixtures, it refers to the mass percentage, and for liquid-liquid mixtures, it refers to the volume percentage.

[0041] Regarding the percentage concentration involved in this application, unless otherwise specified, it refers to the final concentration. The final concentration refers to the proportion of the added component in the system after adding this component.

[0042] For the temperature parameters in this application, unless otherwise specified, it allows both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument.

[0043] Room temperature in this application generally refers to 4°C to 30°C, preferably 20 ± 5°C.

[0044] In this application, the general formula of the term "alcohol solvent" is R1-OH, where R1 is an alkyl group or a cycloalkyl group. The "alcohol solvent with a carbon chain length of C2-C10" means that the number of carbon atoms contained in R is 2-10. Without limitation, the number of carbon atoms can be independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

[0045] In this application, the general formula of the term "ketone solvent" is R2(C=O)R3, where R2 and R3 are each independently an alkyl group or a cycloalkyl group, or R2, R3 and the connected C atom together form a cycloalkyl group. The "ketone solvent with a carbon chain length of C2-C10" means that the total number of carbon atoms contained in the general formula (R2+R3+1) is 2-10. Without limitation, the number of carbon atoms can be independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

[0046] As used herein, the term "alkyl" refers to a monovalent residue formed by removing one hydrogen atom from a saturated hydrocarbon containing primary (normal) carbon atoms, or secondary carbon atoms, or tertiary carbon atoms, or quaternary carbon atoms, or a combination thereof. Suitable examples include, but are not limited to: methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (n-Pr, n-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3), 2-methyl-1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), 2-butyl (s-Bu, s-butyl, -CH(CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2CH(CH3)CH2CH3), 1-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3 and octyl (-(CH2)7CH3).

[0047] As used herein, the term "cycloalkyl" refers to a non-aromatic hydrocarbon containing ring carbon atoms, which can be a monocyclic alkyl group, or a spiroalkyl group, or a bridged cycloalkyl group. Suitable examples include, but are not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

[0048] In some examples of the present application, a method for preparing glycolaldehyde dimer is provided, including the following steps:

[0049] Under the condition of the presence of a catalyst, perform a hydrogenation reduction reaction on glycolide to prepare the glycolaldehyde dimer;

[0050] The catalyst is a supported catalyst, including a carrier and an active component supported on the carrier, and the active component is a ruthenium complex of β-cyclodextrin.

[0051] Understandably, the hydrogenation reduction reaction is carried out in the presence of hydrogen.

[0052] Understandably, a solvent can be further added to the hydrogenation reduction reaction, or not added, and the molten glycolide can be directly used as the solvent.

[0053] Furthermore, glycolaldehyde dimer is a structurally symmetric ester cycloaliphatic diol, and its chemical structure contains 2 primary hydroxyl groups, and there are two configurations, cis- and trans-, as follows:

[0054]

[0055] cis-glycolaldehyde dimer and trans-glycolaldehyde dimer are important intermediates for pesticides and pharmaceutical chemicals respectively. Different configurations correspond to different important pharmaceutical effects and development prospects. However, most of the traditional synthesis methods of glycolaldehyde dimer cannot separate cis-glycolaldehyde dimer and trans-glycolaldehyde dimer, which limits their uses.

[0056] During the research process of this application, it was also found that by regulating the type of solvent in the preparation method of the above glycolaldehyde dimer to regulate the compatibility and spatial stereoselectivity during the reaction, the preparation of cis-glycolaldehyde dimer and trans-glycolaldehyde dimer can be realized respectively, which lays a foundation for the application of cis-glycolaldehyde dimer and trans-glycolaldehyde dimer in different scenarios, and is conducive to the purification synthesis of various crystal forms in related products such as medicine and pesticide, especially conducive to obtaining a crystal form that is stable and efficient at room temperature.

[0057] Specifically, the glycolaldehyde dimer is cis-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a first solvent, and the first solvent is one or more of alcohol solvents.

[0058] In some examples, the first solvent is one or more of alcohol solvents with a carbon chain length of C2-C10. Further, the first solvent is one or more of isopropanol, isobutanol, isopentanol, isohexanol and isooctanol.

[0059] Specifically, the glycolaldehyde dimer is trans-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a second solvent, and the second solvent is one or more of ketone solvents.

[0060] In some of these examples, the second solvent is one or more of ketone solvents with a carbon chain length of C2 - C10. Further, the second solvent is one or more of acetone, methyl ethyl ketone, butanone, pentanone, hexanone, octanone, and cyclohexanone.

[0061] In addition, in some of these examples, the mass ratio of the glycolide to the first solvent or the second solvent is (20 - 100):100. Specifically, the mass ratio of the glycolide to the first solvent or the second solvent includes, but is not limited to: 20:100, 30:100, 40:100, 50:100, 60:100, 70:100, 80:100, 90:100, 20:100.

[0062] In some of these examples, the mass ratio of the catalyst to the glycolide is (2 - 10):100. Specifically, the mass ratio of the catalyst to the glycolide includes, but is not limited to: 2:100, 3:100, 4:100, 5:100, 6:100, 7:100, 8:100, 9:100, 10:100.

[0063] In some of these examples, the reaction temperature of the hydrogenation reduction reaction is 100°C - 150°C. Specifically, the reaction temperature of the hydrogenation reduction reaction includes, but is not limited to: 100°C, 110°C, 120°C, 130°C, 140°C, 150°C.

[0064] In some of these examples, the reaction time of the hydrogenation reduction reaction is 4h - 5h. Specifically, the reaction time of the hydrogenation reduction reaction includes, but is not limited to: 4h, 4.5h, 5h.

[0065] In some of these examples, during the hydrogenation reduction reaction, hydrogen is introduced and the reaction pressure is maintained at 1.5MPa - 2.5MPa. Specifically, the reaction pressure includes, but is not limited to: 1.5MPa, 2MPa, 2.5MPa.

[0066] It can be understood that before introducing hydrogen, the air in the reaction environment is removed by means of vacuum pumping and nitrogen replacement, and then hydrogen is introduced.

[0067] In some of these examples, after the hydrogenation reduction reaction, there is also a post-treatment step:

[0068] The reaction solution after the hydrogenation reduction reaction is filtered to remove the catalyst, the filtrate is cooled, the precipitated solid is collected and dried to prepare the glycolaldehyde dimer.

[0069] Through the above simple post-treatment, a glycolaldehyde dimer with a relatively high purity can be obtained, especially cis-glycolaldehyde dimer and trans-glycolaldehyde dimer can be obtained respectively.

[0070] Understandably, the cooling method can be medium cooling or natural cooling. Usually, cooling from the reaction temperature to room temperature can cause the solid to precipitate, or it can be further cooled to 0 - 5°C to make the solid precipitation more complete. The collection method can be suction filtration, and the drying method can be directly carried out under negative pressure drying on the basis of suction filtration to simplify the operation, or it can be further vacuum dried. Without limitation, the temperature of vacuum drying is 30°C - 60°C, and the pressure is -0.05 MPa - -0.1 MPa. During the suction filtration process, fresh solvent the same as that in the reaction process can also be added for washing.

[0071] In addition, in some of these examples, regarding the catalyst, the molar ratio of β-cyclodextrin to ruthenium element in the active component is 1:(3 - 6). Specifically, the molar ratio of β-cyclodextrin to ruthenium element includes but is not limited to: 1:3, 1:4, 1:5, 1:6.

[0072] In some of these examples, the carrier is a carbon-based material. Without limitation, the carbon-based material can be one or more of activated carbon, carbon nanotubes, and graphene. Further, the activated carbon is non-polar. Understandably, the activated carbon is commercially available medical-grade activated carbon.

[0073] In some of these examples, the specific surface area of the carrier is 800 - 1200 m 3 / g, and the total pore volume is 0.6 - 1.8 mL / g. Using the carbon-based material with this specific surface area and total pore volume can effectively adsorb β-cyclodextrin (β-CD) and stabilize ruthenium nanoparticles.

[0074] In some of these examples, the ruthenium loading (wt%) in the catalyst is 8% - 12%. Specifically, the ruthenium loading in the catalyst includes but is not limited to: 8%, 9%, 10%, 11%, 12%.

[0075] In some of these examples, the preparation steps of the catalyst include:

[0076] Mix β-cyclodextrin, ruthenium chloride, and water, and add a reducing agent under stirring to carry out a reduction reaction to prepare an active component solution;

[0077] Add a carrier to the active component solution, stir, filter, and dry to prepare the catalyst.

[0078] In some of these examples, the reducing agent is one or more of sodium borohydride, potassium borohydride, and lithium aluminum hydride.

[0079] Without limitation, the preparation process of the catalyst is as shown below:

[0080]

[0081] Among them, β-CD refers to β-cyclodextrin, and its structure is shown as follows:

[0082]

[0083] β-CD is a cyclic oligosaccharide composed of seven D-(+)-glucopyranose units linked by α-1,4-glycosidic bonds, presenting a truncated conical shape, and forms a complex with the catalytically active metal ion Ru 3+ As a ligand of the metal ion, β-CD shortens the distance between the substrate and the active center, promoting Ru + / Ru 0 to nucleophilically attack the carbonyl carbon atom (C=O), increasing the reaction rate, enabling the hydrogenation of glycolide to generate glycolaldehyde dimer. Especially under the combined action of a solvent with a specific spatial structure, different conformations of glycolaldehyde dimer are generated.

[0084] Without limitation, first prepare an aqueous solution of β-cyclodextrin, and then mix it with an aqueous solution of ruthenium chloride. The preparation method of the aqueous solution of β-cyclodextrin includes: mixing β-cyclodextrin with water and stirring while heating to 45°C to 65°C.

[0085] Without limitation, the mixing time of β-cyclodextrin, ruthenium chloride and water is 15 min to 25 min.

[0086] Without limitation, the temperature of the reduction reaction is room temperature and the time is 1 h to 3 h. It can be understood that during the addition of the reducing agent, the stirring should be intense.

[0087] Without limitation, after adding a carrier to the active component solution, the stirring time can be 40 min to 80 min, and drying can be carried out in a nitrogen atmosphere at 90°C to 110°C for 48 h to 72 h. <s

[0088] The following are specific examples. Unless otherwise specified, the raw materials used in the examples are commercially available products.

[0089] (1) The activated carbon used in the examples: the specific surface area is 1050 m 3 / g, the total pore volume is 1.1 mL / g, and it is medical-grade activated carbon.

[0090] (2) The preparation method of the catalyst used in the examples is as follows:

[0091] In a 2000 mL beaker, add 500 mL of deionized water and 76 g (0.3 mol) of ruthenium(III) chloride trihydrate (RuCl3·3H2O); prepare an aqueous solution by heating 113.5 g (0.1 mol) of β-cyclodextrin and 400 mL of deionized water to 50 °C and stirring; mix the ruthenium(III) chloride aqueous solution and the β-cyclodextrin aqueous solution, and stir the mixture for 20 min. Under vigorous stirring, slowly add a newly prepared solution of 28.4 g (0.75 mol) of sodium borohydride (NaBH4) and 100 mL of deionized water.

[0092] Stir the resulting reaction solution at room temperature for 2 h to prepare a ruthenium-based metal β-cyclodextrin aqueous suspension colloid solution, then add 140 g of activated carbon, and continue stirring for 60 min. Filter to collect the catalyst, wash it 3 times with 500 mL of deionized water, and dry it in a nitrogen atmosphere at 100 °C for 48 h after thorough washing.

[0093] The prepared catalyst is Ru-β-CD / C, where β-CD is β-cyclodextrin complexed with Ru element and is also the complexing ligand of this catalyst. The ruthenium (Ru) loading can be obtained by ICP-MS elemental analysis, and the average value is 10.0 ± 0.2 wt%.

[0094] (3) GC-MS was used for in-process control during the reaction and for the determination of different structural forms of 1,4-dioxane-2,5-diol in the products in the examples. The specific detection conditions are as follows:

[0095] ① GC conditions: Carrier gas He, column temperature maintained at 130 °C for 3 min, programmed temperature increase to 280 °C at a rate of 15 °C / min,

[0096] Chromatographic column: DB-5 60 m × 0.25 mm;

[0097] ② MS conditions: EI source, ion source temperature 200 °C, interface temperature 280 °C, scanning range m / z 40 - 600.

[0098] The reaction process involved in the examples is as follows:

[0099]

[0100] Among them, type I solvent refers to alcohol solvents, and type II solvent refers to ketone solvents.

[0101] Example 1

[0102] In a 2 L autoclave, 1000 g of glycolide and 60 g of the above-prepared Ru-β-CD / C were added. The autoclave was sealed, evacuated, and purged with nitrogen three times continuously. Hydrogen was charged, and the temperature was raised to 130 °C. The glycolide melted, the stirring was started, hydrogen was supplemented, and the pressure was controlled at 1.5 - 2.0 MPa. The reaction was carried out under insulation for 4 hours. Samples were taken and detected by gas chromatography, and the conversion rate of glycolide reached 100%. After the reaction was completed, the temperature was lowered to about 100 °C, evacuated and purged with nitrogen, the catalyst was filtered out under insulation, and the temperature was further lowered to room temperature to precipitate a solid, obtaining glycolaldehyde dimer (96.67 g of 1,4-dioxane-2,5-diol).

[0103] The prepared glycolaldehyde dimer was detected by GC-MS. The total ion current chromatogram of GC-MS is shown in Figure 1 , and the results are shown in Table 1 below:

[0104] Table 1

[0105] Retention time (min) Molecular weight (EI) Component 12.186 60、88、119、103、120 Peak 1 1,4-Dioxane-2,5-diol (cis-isomer) 12.767 60、88、103、119、120 Peak 2 1,4-Dioxane-2,5-diol (cis-isomer)

[0106] It can be seen that there are mainly two product peaks, peak 1 and peak 2, in the prepared glycolaldehyde dimer. The retention times are peak 1: 12.186 min and peak 2: 12.767 min. The corresponding molecular ion peaks and fragment peaks are the same; only the peak 2 at 12.767 min is slightly weaker than the molecular ion peak at 12.186 min, and the corresponding component has a slightly higher boiling point; the abundances of the 1 and 2 fragment peaks are not completely the same. However, the mass-to-charge ratio is the same (total molecular weight). Therefore, the components corresponding to peak 1 and peak 2 are isomers of each other. Also, because the two major primary hydroxyl groups corresponding to peak 1 and peak 2 are not completely symmetric and have cis and trans configurations. So the component corresponding to peak 1 is: cis-1,4-dioxane-2,5-diol; the component corresponding to peak 2 is: trans-1,4-dioxane-2,5-diol. Combining the calculation of the peak area, the content of cis-1,4-dioxane-2,5-diol is 39.8%; the content of trans-1,4-dioxane-2,5-diol is 59.7%; the content of other components (the component with a retention time of 8.819) is 0.50%.

[0107] Example 2

[0108] In a 2L autoclave, 1000g of glycolide isopropanol solution (mass concentration of glycolide is 20%) is added, and then 60g of the same hydrogenation catalyst as in Example 1 is added. The autoclave is sealed, evacuated, and purged with nitrogen for 3 consecutive operations. Hydrogen is charged, the temperature is raised to 130°C, stirring is started, and nitrogen is used for pressure compensation. The pressure is controlled at 1.5 - 2.0 MPa, and the reaction is carried out under insulation for 4 hours. Samples are taken and analyzed by gas chromatography. The conversion rate of lactide reaches 100%. After the reaction is completed, the temperature is lowered to about 40°C for safe evacuation. After evacuation and nitrogen replacement, the catalyst is filtered out at 40°C under insulation. The filtrate is cooled to 0 - 5°C, and cis-1,4-dioxane-2,5-diol precipitates. It is centrifuged and filtered, washed with fresh solvent multiple times, and dried under negative pressure to obtain 136.9g of the product.

[0109] The GC-MS total ion current chromatogram of the prepared glycolaldehyde dimer with 98.3% content of cis-1,4-dioxane-2,5-diol and 1.7% content of trans-1,4-dioxane-2,5-diol is shown in Figure 2 .

[0110] Example 3

[0111] In a 2L autoclave, 1000g of glycolide acetone solution (mass concentration of glycolide is 20%) is added, and then 60g of the same hydrogenation catalyst as in Example 1 is added. The autoclave is sealed, evacuated, and purged with nitrogen for 3 consecutive operations. Hydrogen is charged, the temperature is raised to 130°C, stirring is started, and nitrogen is used for pressure compensation. The pressure is controlled at 1.5 - 2.0 MPa, and the reaction is carried out under insulation for 4 hours. Samples are taken and analyzed by gas chromatography. The conversion rate of lactide reaches 100%. After the reaction is completed, the temperature is lowered to about 40°C for safe evacuation. After evacuation and nitrogen replacement, the catalyst is filtered out at 40°C under insulation. The filtrate is cooled to 0 - 5°C, and trans-1,4-dioxane-2,5-diol precipitates. It is centrifuged and filtered, washed with fresh solvent multiple times, and dried under negative pressure to obtain 127.8g of the product.

[0112] The GC-MS total ion current chromatogram of the prepared glycolaldehyde dimer with 1.2% content of cis-1,4-dioxane-2,5-diol and 98.8% content of trans-1,4-dioxane-2,5-diol is shown in Figure 3 .

[0113] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity in description, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope recorded in this specification.

[0114] The above-described embodiments merely represent several implementation manners of the present application, facilitating a specific and detailed understanding of the technical solutions of the present application. However, it should not be construed as a limitation on the scope of patent protection of the application. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can be made, and these all fall within the protection scope of the present application. It should be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments based on the technical solutions provided by the present application are all within the protection scope of the appended claims of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the content of the appended claims, and the specification and the drawings can be used to interpret the content of the claims.

Claims

1. A preparation method of glycolaldehyde dimer, characterized in that, It includes the following steps: Under the presence of a catalyst, glycolide is subjected to a hydrogenation reduction reaction to prepare the glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of hydrogen; The catalyst is a supported catalyst, including a carrier and an active component supported on the carrier, and the active component is a ruthenium complex of β-cyclodextrin; The preparation steps of the catalyst include: Mix β-cyclodextrin, ruthenium chloride and water, and add a reducing agent under stirring to carry out a reduction reaction to prepare an active component solution; Add a carrier to the active component solution, stir, filter and dry to prepare the catalyst.

2. The preparation method of glycolaldehyde dimer according to claim 1, characterized in that, The glycolaldehyde dimer is cis-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a first solvent, and the first solvent is one or more of alcohol solvents.

3. The preparation method of glycolaldehyde dimer according to claim 2, wherein The first solvent is one or more of alcohol solvents with a carbon chain length of C2-C10.

4. The preparation method of glycolaldehyde dimer according to claim 3, wherein, The first solvent is one or more of isopropanol, isobutanol, isopentanol, isohexanol and isooctanol.

5. The preparation method of glycolaldehyde dimer according to claim 1, characterized in that, The glycolaldehyde dimer is trans-glycolaldehyde dimer, and the hydrogenation reduction reaction is carried out in the presence of a second solvent, and the second solvent is one or more of ketone solvents.

6. The preparation method of glycolaldehyde dimer according to claim 5, characterized in that, The second solvent is one or more of ketone solvents with a carbon chain length of C2-C10.

7. The preparation method of glycolaldehyde dimer according to claim 6, characterized in that, The second solvent is one or more of acetone, methyl ethyl ketone, butanone, pentanone, hexanone, octanone and cyclohexanone.

8. The preparation method of glycolaldehyde dimer according to any one of claims 2 to 7, characterized in that, The mass ratio of the glycolide to the first solvent or the second solvent is (20-100):

100.

9. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, The mass ratio of the catalyst to the glycolide is (2-10):

100.

10. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, The conditions of the hydrogenation reduction reaction include at least one of the following features (1)-(3): (1) The reaction temperature is 100°C-150°C; (2) The reaction time is 4h-5h; (3) Hydrogen is introduced and the reaction pressure is maintained at 1.5MPa-2.5MPa.

11. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, In the active component, the molar ratio of β-cyclodextrin to ruthenium element is 1:(3-6).

12. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, The carrier is a carbon-based material.

13. The preparation method of glycolaldehyde dimer according to claim 12, characterized in that, The specific surface area of the carbon-based material is 800 to 1200 m 3 / g, and the total pore volume is 0.6 to 1.8 mL / g.

14. The preparation method of glycolaldehyde dimer according to claim 12, wherein, The carbon-based material is one or more of activated carbon, carbon nanotubes and graphene.

15. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, In the catalyst, the ruthenium loading is 8%-12%.

16. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, The reducing agent is one or more of sodium borohydride, potassium borohydride and lithium aluminum hydride.

17. The preparation method of glycolaldehyde dimer according to any one of claims 1 to 7, characterized in that, After the hydrogenation reduction reaction, a post-treatment step is further included: Filter the reaction solution after the hydrogenation reduction reaction to remove the catalyst, cool the filtrate, collect the precipitated solid, and dry it to prepare the glycolaldehyde dimer.

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