A new process for the efficient synthesis of hydroxy acids and their derivatives

Abstract

The present invention relates to the field of new material chemicals, and in particular to widely used degradable green materials with excellent biocompatibility, degradability and excellent mechanical processing properties, providing key raw materials for hydroxy esters, glycolides, lactides and / or mixed lactides. The technology reports a new process for efficiently preparing hydroxy acids and their derivatives by reacting trihalohydrins or halogenated carbonyl compounds with alcohols or water, and has excellent cost competitiveness, safe and simple operation, high product purity, environmental friendliness and resource sustainability.

Description

[Technical field]

[0001] The present invention relates to the field of new material chemicals, and in particular to widely used degradable green materials with excellent biocompatibility, degradability and excellent mechanical processing properties, providing key raw materials for compounds such as hydroxy esters, glycolides, lactides and mixed lactides. The technology reports a new process for efficiently preparing hydroxy acids and their derivatives by reacting trihalohydrins or halogenated carbonyl compounds with alcohols or water, and has significant cost competitiveness, safe and simple operation, high product purity, environmental friendliness and resource sustainability. [Background technology]

[0002] It is reported that the global plastics industry output will reach 330 million tons by 2050. 9 Tons of plastics or recycled microplastics can survive in surface water, groundwater, soil and organisms for decades or even hundreds of years due to natural environmental factors such as acid and alkali erosion and oxidation. This long decomposition process has already brought serious harm to the human ecological environment.

[0003] In recent years, with the issuance of multiple batches of legal documents on "plastic restriction" by the state, the biodegradable plastic industry has entered a stage of rapid development. Its advantage is that it can be degraded in a short time and by microorganisms in nature, and the substances produced by degradation will not cause pollution to human health, animals, plants and the natural environment. 2 Copolymers (PPC, PPC-P), polylactic acid (PLA), polyhydroxyalkanoates (PHA) and polyglycolic acid (PGA) are important biodegradable plastic products that promote my country's reduction of plastic waste and realization of the "dual carbon" goals. They are aliphatic polyester polymer materials that can be completely decomposed and have excellent gas barrier properties, biocompatibility, biodegradability and excellent mechanical processing properties. Therefore, they are widely used in biomedicine, packaging, oil and gas extraction and other fields.

[0004] Among them, the synthesis of PGA mainly adopts the direct condensation polymerization of glycolic acid and the ring-opening polymerization of glycolide. Both processes start from the same glycolic acid raw material. As the smallest α-hydroxy acid and the smallest molecular weight fruit acid, glycolic acid is the simplest aliphatic hydroxy acid. The large-scale production of glycolic acid is mainly achieved by chemical synthesis. At present, there are many glycolic acid production process routes, mainly (1) chloroacetic acid hydrolysis method: chloroacetic acid is hydrolyzed under alkaline conditions of sodium hydroxide to obtain the finished product. This method consumes a large amount of alkali, increases costs and is difficult to separate after post-treatment, and the purity is low, which affects its use; (2) formaldehyde carbonylation method: formaldehyde, carbon monoxide and water catalyzed by acidic catalyst react under high temperature and high pressure and then refined to obtain solid glycolic acid. This method has high requirements on the corrosion resistance of the equipment, the catalyst cannot be reused and is mixed in glycolic acid, thereby reducing the purity of the product; (3) cyanidation method: formaldehyde and hydrocyanic acid are used as raw materials to first synthesize hydroxyacetonitrile, and then hydrolyzed to obtain glycolic acid. This method uses highly toxic cyanide, which poses great environmental pollution and safety pressures; (4) Dimethyl oxalate hydrogenation hydrolysis method: The raw material of dimethyl oxalate is synthesis gas, which is the main production process in China. The difficulty lies in the development of an efficient hydrogenation catalyst. If the catalytic effect is not good, a large amount of methanol by-product and over-hydrogenated ethylene glycol will be produced, resulting in reduced atomic utilization and selectivity. At the same time, glycolic acid is produced by the hydrolysis of methyl glycolate, and incomplete hydrolysis will also lead to a decrease in product yield; (5) Although other routes such as ethylene glycol selective oxidation, oxalic acid electrolysis, and bio-glycerol catalytic oxidation can produce glycolic acid, further exploration is needed to achieve industrialization.

[0005] In summary, based on all the currently disclosed technologies, there are many problems such as severe reaction conditions, high equipment requirements, toxic raw materials, high costs, subsequent separation difficulties and environmental pollution, which seriously limit the large-scale production of glycolic acid and violate the original intention of green production. Therefore, there is an urgent need to find a green and sustainable method for large-scale production of crystalline glycolic acid. This technology reports a new process for the efficient preparation of hydroxy acids and their derivatives by reacting trihalohydrins or halogenated carbonyl compounds with alcohols or water. The process has significant cost competitiveness, simple operation, process safety, high product purity, environmental friendliness and resource sustainability. [Summary of the invention]

[0006] The present invention is aimed at the above-mentioned deficiencies and provides a synthesis process for efficiently preparing hydroxy acids and their derivatives by reacting trihalohydrins or halogenated carbonyl compounds with alcohols or water, as shown in reaction formula (I-II). The process has significant cost competitiveness, simple operation, safe process, high product purity, environmental friendliness and resource sustainability.

[0007]

[0008] Where R 1 , R2 , R 3 or R 4 (including multiple R in the same structure 4 ) are independently hydrogen, or a straight-chain or branched aliphatic hydrocarbon group containing 1 to 24 carbon atoms, or a (hetero) aromatic hydrocarbon group containing 4 to 24 carbon atoms; X 1 , X 2 , or X 3 are independently F, Cl, Br, I. Preferably, X is Cl or OCH 3 or OCH 2 CH 3 .

[0009] The solvent can be selected from at least one of substituted or unsubstituted aromatic hydrocarbons, straight or branched aliphatic hydrocarbons, (sub) sulfones, amides, ethers, alcohols, esters, ketones, nitrile, carboxylic acids, water, amines, carbonates, ionic liquids, and supercritical carbon dioxide containing 1-24 carbons, or the substrate itself serves as a solvent medium at the same time. Preferably, the solvent is methanol, ethanol, ethyl acetate, butyl acetate, water, dimethyl sulfoxide, cyclopentane, methylene chloride, ethylene dichloride, dimethyl carbonate, diethyl carbonate, ethylene carbonate, propylene carbonate, chloroform, carbon tetrachloride, toluene, xylene, acetonitrile, chlorobenzene, dichlorobenzene, anisole, nitrobenzene, heptane, hexane, petroleum ether, dioxane, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, and ethylene glycol dimethyl ether. In step (1), preferably, it is selected from at least one of 10 degrees Celsius to 30 degrees Celsius.

[0010] The temperature is -50°C to 350°C. Preferably, it is selected from 0°C to 300°C. More preferably, it is selected from 50°C to 280°C.

[0011] The pressure is 0.001 atm-200 atm. Preferably, the pressure is 0.1 atm-100 atm.

[0012] The additives are reaction accelerators, synergists, catalysts, oxidants, polymerization inhibitors, reducing agents and / or functional additives.

[0013] Compared with the prior art, the technical solution provided by the present invention has the following significant effects:

[0014] 1. The hydroxy acid and its derivatives prepared by the above method can be used as key raw materials or intermediates for synthesizing degradable and compatible polymer materials.

[0015] 2. Significant cost competitiveness.

[0016] 3. Simple operation and safe process.

[0017] 4. The post-processing is simple and the product purity is high.

[0018] 5. Environmental friendliness and resource sustainability.

[0019] The gist of the present invention is further described below in conjunction with specific embodiments: [Specific implementation method]

[0020] Embodiment 1:

[0021]

[0022] At room temperature, 15 g of trichloroethanol, 130 mg of nickel chloride and 100 mL of distilled water were added to a 250 mL reaction bottle in sequence, and the system was heated to 160 ° C for 3 hours under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 7.2 g of glycolic acid as a colorless solid, with a yield of 95%.

[0023] Embodiment 2:

[0024]

[0025] At room temperature, 16.1 g of 1,1,1-trichloro-2-propanol, 136 mg of zinc chloride and 100 mL of distilled water were added to a 250 mL reaction bottle in sequence, and the system was heated to 130 ° C for 2 h under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 8.4 g of lactic acid colorless liquid, with a yield of 93%.

[0026] Embodiment three:

[0027]

[0028] At room temperature, 22.5 g of 2,2,2-trichloro-1-phenylethanol, 336 mg of platinum chloride and 100 mL of distilled water were added to a 250 mL reaction bottle in sequence, and the system was heated to 130 ° C for 2 h under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 14.4 g of mandelic acid as a white solid, with a yield of 95%.

[0029] Embodiment 4:

[0030]

[0031] At room temperature, 9.4 g of chloroacetic acid, 379 mg of tin dichloride and 50 mL of distilled water were added to a 100 mL reaction bottle in sequence, and the system was heated to 110 ° C for 1 hour under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 7.4 g of glycolic acid as a colorless solid, with a yield of 97%.

[0032] Embodiment five:

[0033]

[0034] At room temperature, 10.8 g of 2-chloropropionic acid, 520 mg of tin tetrachloride and 50 mL of distilled water were added to a 100 mL reaction bottle in sequence, and the system was heated to 110 ° C for 1 hour under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 8.6 g of lactic acid as a colorless solid, with a yield of 96%.

[0035] Embodiment six:

[0036]

[0037] At room temperature, 7.8 g of chloroacetaldehyde, 272 mg of zinc chloride and 50 mL of distilled water were added to a 100 mL reaction bottle in sequence, and the system was heated to 130 ° C for 1 hour under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 5.7 g of ethanolaldehyde colorless liquid, with a yield of 95%.

[0038] Embodiment seven:

[0039]

[0040] At room temperature, 10.8 g of methyl chloroacetate, 379 mg of tin dichloride and 80 mL of distilled water were added to a 200 mL reaction bottle in sequence, and the system was heated to 130 ° C for 2 h under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 8.6 g of methyl glycolate as a colorless liquid, with a yield of 96%.

[0041] Embodiment eight:

[0042]

[0043] At room temperature, 15 g of trichloroethanol, 177 mg of palladium chloride, 10 mL of methanol and 60 mL of chlorobenzene were added to a 250 mL reaction bottle in sequence, and the system was heated to 130 ° C for 3 hours under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the obtained residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 7.2 g of methyl glycolate as a colorless liquid, with a yield of 95%.

[0044] Embodiment nine:

[0045]

[0046] At room temperature, 15 g of trichloroethanol, 354 mg of palladium chloride, 20 mL of methanol and 60 mL of chlorobenzene were added to a 250 mL reaction bottle in sequence, and the system was heated to 150 ° C for 4 hours under sufficient stirring. After the reaction was completed, the mixed solution was concentrated under reduced pressure, and the residue was eluted with hexane / ethyl acetate on a silica gel column chromatography to obtain 9.5 g of methyl methoxyacetate as a colorless liquid, with a yield of 91%.

[0047] It should be emphasized that the above embodiments are merely illustrative and not restrictive. Based on the disclosure of this application, any adjustment or change in reaction conditions or parameters that may be commonly adopted by practitioners will not deviate from the gist of the present invention. The scope of protection of this patent shall be based on the relevant rights record items.

Claims

1. A new process for efficiently synthesizing hydroxy acids and their derivatives. As shown in reaction formula (I-II), under reaction conditions, a trihalohydrin represented by structural formula A or a halogenated carbonyl compound represented by structural formula B reacts with R3OH (alcohol or water) to prepare a hydroxy acid represented by structural formula C or D and its derivatives (general formula I-II): Wherein R1, R2, R3 or R4 (including multiple R4 in the same structure) are independently hydrogen, or a straight-chain or branched aliphatic hydrocarbon group containing 1 to 24 carbon atoms, or a (hetero) aromatic hydrocarbon group containing 4 to 24 carbon atoms; X1, X2, or X3 are independently F, Cl, Br, I. The conditions are at least one of a solvent, a temperature, a pressure (or a vacuum), and an additive.

2. According to claim (1), the hydroxy acid and its derivative C or D that can be prepared by the present invention include the following exemplary but non-limiting structures or mixtures thereof:

3. According to claim (1), the solvent can be selected from at least one of substituted or unsubstituted aromatic hydrocarbons, linear or branched aliphatic hydrocarbons, (sub)sulfones, amides, ethers, alcohols, esters, ketones, nitriles, carboxylic acids, water, amines, carbonates, ionic liquids, and supercritical carbon dioxide containing 1-24 carbon atoms, or the substrate itself can serve as a solvent medium at the same time.

4. According to claim (1), the temperature is -50°C to 350°C, preferably selected from 0°C to 300°C.

5. According to claim (1), the pressure is 0.001 atm-200 atm. The additive refers to a reaction accelerator, a synergist, a catalyst, an oxidant, an inhibitor, a reducing agent and / or a functional aid. Based on the substrate trihalohydrin A, the additive is used in an amount of 0.001-1000 equivalents.

6. According to claim (1), the hydroxy acid and its derivatives prepared by the above method can be used as key raw materials or intermediates for synthesizing degradable and compatible polymer materials.

Images