CN113149953A - Method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one - Google Patents
Method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one Download PDFInfo
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- CN113149953A CN113149953A CN201911287882.3A CN201911287882A CN113149953A CN 113149953 A CN113149953 A CN 113149953A CN 201911287882 A CN201911287882 A CN 201911287882A CN 113149953 A CN113149953 A CN 113149953A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D317/34—Oxygen atoms
- C07D317/40—Vinylene carbonate; Substituted vinylene carbonates
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one by using diphenyl carbonate as a high-activity green carbonyl source, which comprises the steps of adding 2, 3-butanediol and diphenyl carbonate serving as raw materials into an organic solvent, and carrying out heat preservation and stirring reaction under the action of a catalyst; and carrying out reduced pressure distillation on the obtained reaction solution to remove the solvent, and further recrystallizing to obtain the high-purity 4, 5-dimethyl-1, 3-dioxol-2-one, wherein the method also comprises the steps of washing the recrystallized mother solution by using an alkali liquor, separating to obtain a water phase, and then adjusting the pH value of the water phase to 5-7 to recover phenol.
Description
Technical Field
The invention belongs to the technical field of synthesis of intermediates, and particularly relates to a method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one by using diphenyl carbonate as a green high-activity carbonyl source.
Background
4, 5-dimethyl-1, 3-dioxol-2-one (DMDO) is used as a key intermediate for synthesizing a plurality of medicines, and the medicine effect is improved to a greater extent and the side effect of the medicines is reduced mainly by carrying out specific chemical reaction with some pharmacodynamic groups. In recent years, a series of ester drugs with good curative effect, less toxic and side effect and good stability are continuously developed through structure modification of various drugs, such as: antihypertensive (olmesartan), and antibiotic (lenacilin, prulifloxacin, etc.).
The synthesis method of the compound mainly comprises the following synthesis routes:
(1) phosgene, diphosgene (trichloromethyl chloroformate), triphosgene method: US6117885, US4428806, JP6010571, US448732 and the like propose to obtain the product by using hydroxy butanone as a raw material through the steps of acylation, cyclization, high-temperature hydrogen chloride removal and the like. Phosgene is a toxic chemical gas which is strictly limited to use internationally, so that phosgene is not suitable for industrial production. The phosgene substitute diphosgene and triphosgene can slowly release the virulent phosgene during high-temperature reaction. Meanwhile, the product DMDO is unstable to heat, hydrogen chloride is separated at the high temperature of 160-170 ℃, carbonization and decomposition are easy, the yield is low, the product quality is poor, and the industrial requirement can be met only by further purification. And the hydrogen chloride has strong corrosivity at high temperature in the reaction process and has high requirements on equipment.
(2) Solid phosgene is used as an acylation reagent, and the DMDO is prepared by removing hydrogen chloride by a solvent method, for example, in an article of synthesis of 4, 5-dimethyl-1, 3-dioxol-2-one, such as Indian patent 2013CH00686, Hu Yue and the like, dimethylacetamide or toluene is used as a solvent, and the hydrogen chloride is removed at 90-110 ℃. The method avoids the carbonization and decomposition of products caused by the removal of hydrogen chloride at high temperature without solvent, but the hydrogen chloride generated in the reaction process has strong corrosivity on equipment, and the virulent phosgene is decomposed from the solid phosgene in the reaction.
(3) In U.S. Pat. No. 4,4344881, Strege et al, Americans synthesized DMDO using ethyl trichloroacetate with 2, 3-butanediol as the main raw material, and the reaction yield was up to 88%. Although the method has high yield, the reaction conditions are severe and the requirements on equipment are high, and the hydrogen chloride needs to be removed at 160 ℃.
The Chinese patent with publication number CN103483307A discloses a preparation method of 4, 5-dimethyl-1, 3-dioxol-2-one, which takes 3-hydroxy-2-butanone and dimethyl carbonate as raw materials and comprises the following steps: (1) in a reactor with a rectification reaction device, alkali metal alkoxide is used as a catalyst, fatty ether is used as a solvent, 3-hydroxy-2-butanone and dimethyl carbonate are added according to a certain proportion, a reaction mixture is heated at 60-100 ℃, ester exchange reaction is carried out for 3-6h, and a by-product methanol is synchronously distilled out to obtain monomethyl carbonate-3-hydroxy-2-butyl ketone ester; wherein, the mol ratio of the 3-hydroxy-2-butanone to the dimethyl carbonate is 1: 1-5.0; the addition amount of the alkali metal alkoxide is 1 to 6 percent of the mass of the 3-hydroxy-2-butanone; the dosage of the fatty ether is 3-7 times of the mass of the 3-hydroxy-2-butanone; (2) raising the temperature of the reaction mixture to 110-160 ℃, keeping the temperature for reaction for 2-5h, and continuously distilling off byproducts such as methanol and the like; (3) after the reaction is finished, cooling the reaction mixture to room temperature, and slowly adding concentrated hydrochloric acid to neutralize the reaction catalyst until the pH value of the reaction mixture is about 7; after the dimethyl carbonate is recovered by fractional distillation, a proper amount of fatty ether is evaporated under reduced pressure; cooling the distillation residue to 0-5 ℃, crystallizing, filtering or centrifuging to obtain a crude product of the 4, 5-dimethyl-1, 3-dioxol-2-one. The method adopts alkali metal salt as a catalyst, a large amount of hydrochloric acid is needed for neutralization subsequently, the cost is increased, and after the concentrated hydrochloric acid is added, the dimethyl carbonate can be hydrolyzed, so that the raw materials cannot be recycled.
The invention aims to overcome the defects of the prior art and provide a method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one by using diphenyl carbonate as a high-activity green carbonyl source. The method has the advantages of simple process, mild reaction conditions, and high yield and purity. The diphenyl carbonate used can be recycled for a plurality of times through simple recovery and regeneration treatment, so that the process has low cost, is easy to implement industrially and has good economic benefit.
The invention relates to a method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one by using diphenyl carbonate as a high-activity green carbonyl source, which specifically comprises the steps of adding 2, 3-butanediol and diphenyl carbonate serving as raw materials into an organic solvent, and carrying out heat preservation and stirring reaction under the action of a catalyst; and distilling the obtained reaction solution under reduced pressure to remove the solvent, and further recrystallizing to obtain the high-purity 4, 5-dimethyl-1, 3-dioxol-2-one.
Preferably, the method further comprises the steps of washing the mother liquor after recrystallization with an alkali liquor, separating to obtain an aqueous phase, and then adjusting the pH of the aqueous phase to 5-7 to recover phenol.
Preferably, the organic solvent comprises more than one of tetrahydrofuran, acetone, dioxane, acetonitrile, 2-methyltetrahydrofuran or dimethylformamide; more preferably, tetrahydrofuran and/or acetonitrile are included.
Preferably, the amine catalyst comprises more than one of pyridine, Triethylamine (TEA), 1,5, 7-triazabicyclo [4.4.0] dec-5-ene (TBD), 7-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene (MTBD), 1, 8-diazabicycloundece-7-ene (DBU) and 4-Dimethylaminopyridine (DMAP), and the use amount of the amine catalyst is 5-20% of the use amount of 2, 3-butanediol by weight.
Preferably, the diphenyl carbonate is used in an amount of 1.5 to 3.0 times by weight of the 2, 3-butanediol.
Preferably, the heat preservation temperature is 20-50 ℃, and the heat preservation time is 1-5 h.
Preferably, the solvent used for recrystallization comprises more than one of methanol, ethanol, dichloromethane, chloroform, toluene, n-hexane, ethyl acetate or petroleum ether; more preferably, the solvent includes one or more of toluene, n-hexane, and ethyl acetate.
Preferably, the alkali liquor comprises more than one of NaOH and KOH.
Preferably, the pH value of the water phase is adjusted by dropwise adding a hydrochloric acid solution into the water phase or introducing carbon dioxide gas into the water phase.
The reaction mechanism of the present invention is as follows:
compared with the prior art, the invention has the following beneficial effects:
(1) the diphenyl carbonate replaces phosgene raw materials, the process is safe and environment-friendly, and the raw material diphenyl carbonate can be regenerated by the byproduct phenol and recycled for multiple times, so that the process is low in cost and has good economic benefit.
(2) Compared with the traditional process for preparing DMDO by three steps of acylation, cyclization and high-temperature dehydrochlorination, the invention can prepare the target product by one-step reaction, and has safe and reliable production and simple operation. Meanwhile, the defects that the product is easy to be carbonized and decomposed during high-temperature dehydrochlorination, the yield is low, the product quality is poor, and the hydrochloric acid has strong corrosivity at high temperature in the reaction process and has high requirements on equipment are avoided.
(3) Compared with the prior art, the method has the advantages of simplified production process, mild reaction conditions, higher product purity, safety, environmental protection and low production cost, and the diphenyl carbonate can be regenerated by the byproduct phenol.
(4) Since diphenyl carbonate is used as a raw material, phenol which is a by-product of the reaction is stable and difficult to be reversibly reacted, and thus the reaction can be carried out at a relatively low temperature.
(5) Washing the crystallized mother liquor by using alkali liquor, and enabling the phenol to exist in a soluble salt form and a water phase, so that the phenol can be recycled.
Detailed Description
In order to better explain the present invention and to facilitate the understanding of the technical solutions of the present invention, the present invention is further described in detail below. However, the following examples are only illustrative of the present invention and do not represent or limit the scope of the present invention, which is defined by the claims.
Example 1
9.01g (0.10 mol) of 2, 3-butanediol, 22g (0.11 mol) of diphenyl carbonate, 0.28g of TBD and 200mL of tetrahydrofuran are sequentially added into a dry 500mL four-neck round-bottom flask, the temperature is raised to 40 ℃ under stirring, the reaction is kept for 4 hours, the solvent is evaporated by rotary drying, and 10.26g of DMDO white crystals are obtained after recrystallization and drying by petroleum ether, the GC purity is 99.1 percent and the molar yield is 90.0 percent.
Example 2
9.01g (0.10 mol) of 2, 3-butanediol, 25g (0.12 mol) of diphenyl carbonate, 0.9g of TEA and 200mL of tetrahydrofuran are sequentially added into a dry 500mL four-neck round-bottom flask, the temperature is raised to 30 ℃ under stirring, the reaction is kept for 2h, the solvent is evaporated by rotary drying, and 10.49g of DMDO white crystals are obtained after recrystallization from petroleum ether and drying, the GC purity is 99.3 percent, and the molar yield is 92.0 percent.
Example 3
9.01g (0.10 mol) of 2, 3-butanediol, 25g (0.12 mol) of diphenyl carbonate, 0.28g of DMAP and 200mL of acetonitrile are sequentially added into a dry 500mL four-neck round-bottom flask, the temperature is raised to 40 ℃ under stirring, the reaction is kept for 4h, the solvent is removed by spin-drying, and the 10.38DMDO white crystal is obtained by recrystallization from normal hexane and drying, the GC purity is 99.0 percent and the molar yield is 91.0 percent.
Example 4
9.01g (0.10 mol) of 2, 3-butanediol, 22g (0.11 mol) of diphenyl carbonate, 0.28g of TBD and 200mL of 2-methyltetrahydrofuran are sequentially added into a dry 500mL four-neck round-bottom flask, the temperature is raised to 50 ℃ under stirring, the reaction is kept for 2 hours, the solvent is evaporated by spin drying, and the mixture is recrystallized by ethyl acetate and dried to obtain 10.40g of DMDO white crystals with the GC purity of 99.0 percent and the molar yield of 91.2 percent.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (9)
1. A process for preparing 4, 5-dimethyl-1, 3-dioxol-2-one, characterized in that: adding 2, 3-butanediol and diphenyl carbonate serving as raw materials into an organic solvent, and carrying out heat preservation and stirring reaction under the action of a catalyst; removing the solvent from the obtained reaction liquid by reduced pressure distillation and further recrystallizing to obtain the high-purity 4, 5-dimethyl-1, 3-dioxol-2-one, wherein the temperature for the heat preservation stirring reaction is
2. The method of claim 1, wherein: the method also comprises the steps of washing the mother liquor after recrystallization by using alkali liquor, separating to obtain an aqueous phase, and then adjusting the pH value of the aqueous phase to 5-7 to recover phenol.
3. The method according to claim 1 or 2, characterized in that: the organic solvent comprises more than one of tetrahydrofuran, acetone, dioxane, ethylene wax, 2-methyl tetrahydrofuran or dimethylformamide.
4. The method according to claim 1 or 2, characterized in that: the catalyst comprises pyridine, Triethylamine (TEA), 1,5, 7-triazabicyclo [4.4.0]Dec-5-ene (TBD), 7-methyl-1, 5, 7-triazabicyclo [4.4.0]More than one of deca-5-ene (MTBD), 1, 8-diazabicycloundec-7-ene (DBU), 4-Dimethylaminopyridine (DMAP), wherein the amine catalyst is present in an amount of 2,3-T diol by weight
5. The method according to claim 1 or 2, characterized in that: the diphenyl carbonate is used in an amount of 2,3-7 diols by weight
6. The method according to claim 1 or 2, characterized in that: the reaction time of the heat preservation stirring is as follows
7. The method according to claim 1 or 2, characterized in that: the solvent for recrystallization comprises more than one of methanol, ethanol, dichloromethane, chloroform, toluene, n-hexane, ethyl acetate or petroleum ether.
8. The method according to claim 1 or 2, characterized in that: the alkali liquor comprises more than one of NaOH and KOH.
9. The method according to claim 1 or 2, characterized in that: and the step of adjusting the pH value of the water phase comprises the step of dropwise adding a hydrochloric acid solution into the water phase or introducing carbon dioxide gas into the water phase.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911287882.3A CN113149953A (en) | 2019-12-16 | 2019-12-16 | Method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one |
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| CN201911287882.3A CN113149953A (en) | 2019-12-16 | 2019-12-16 | Method for preparing 4, 5-dimethyl-1, 3-dioxol-2-one |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113912580A (en) * | 2021-11-03 | 2022-01-11 | 瑞孚信江苏药业股份有限公司 | Method for purifying 4- (hydroxymethyl) -5-methyl- [1,3] dioxol-2-one |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4344881A (en) * | 1981-02-02 | 1982-08-17 | The Dow Chemical Company | Process for making alkylene carbonates |
| GB2280672A (en) * | 1993-08-06 | 1995-02-08 | Exxon Chemical Patents Inc | Process for the production of alcohol carbonates |
| CN101654448A (en) * | 2008-08-20 | 2010-02-24 | 厚成株式会社 | Method of manufacturing vinylethylene carbonate |
| CN103483307A (en) * | 2013-09-27 | 2014-01-01 | 六安科瑞达新型材料有限公司 | Preparation method of 4,5-dimethyl-1,3-dioxole-2-ketone |
| CN109942534A (en) * | 2019-03-06 | 2019-06-28 | 珠海市赛纬电子材料股份有限公司 | A kind of thricarbonate vinyl acetate and preparation method thereof |
-
2019
- 2019-12-16 CN CN201911287882.3A patent/CN113149953A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4344881A (en) * | 1981-02-02 | 1982-08-17 | The Dow Chemical Company | Process for making alkylene carbonates |
| GB2280672A (en) * | 1993-08-06 | 1995-02-08 | Exxon Chemical Patents Inc | Process for the production of alcohol carbonates |
| CN101654448A (en) * | 2008-08-20 | 2010-02-24 | 厚成株式会社 | Method of manufacturing vinylethylene carbonate |
| CN103483307A (en) * | 2013-09-27 | 2014-01-01 | 六安科瑞达新型材料有限公司 | Preparation method of 4,5-dimethyl-1,3-dioxole-2-ketone |
| CN109942534A (en) * | 2019-03-06 | 2019-06-28 | 珠海市赛纬电子材料股份有限公司 | A kind of thricarbonate vinyl acetate and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| EK RAJ BARAL等: ""Diphenyl Carbonate: A Highly Reactive and Green Carbonyl Source for the Synthesis of Cyclic Carbonates"", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| 潘岩: ""4,5-二甲基-1,3-二氧杂环戊烯-2-酮（DMDO）合成工艺研究"", 《信阳农林学院学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113912580A (en) * | 2021-11-03 | 2022-01-11 | 瑞孚信江苏药业股份有限公司 | Method for purifying 4- (hydroxymethyl) -5-methyl- [1,3] dioxol-2-one |
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Application publication date: 20210723 |