CN109232184B - Method for improving optical purity of L-isopulegol through chiral resolution - Google Patents
Method for improving optical purity of L-isopulegol through chiral resolution Download PDFInfo
- Publication number
- CN109232184B CN109232184B CN201811166606.7A CN201811166606A CN109232184B CN 109232184 B CN109232184 B CN 109232184B CN 201811166606 A CN201811166606 A CN 201811166606A CN 109232184 B CN109232184 B CN 109232184B
- Authority
- CN
- China
- Prior art keywords
- isopulegol
- linalool
- agent
- resolving
- purity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/88—Separation; Purification; Use of additives, e.g. for stabilisation by treatment giving rise to a chemical modification of at least one compound
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Abstract
The invention provides a method for improving the optical purity of L-isopulegol by chiral resolution. Reacting D, L-isopulegol and a resolving agent L-linalool in a dispersing agent and an auxiliary agent at 70-80 ℃ for 3-4 hours, cooling to 10-25 ℃, and performing centrifugal separation to obtain an intermediate L-isopulegol.L-linalool; and (3) carrying out alkali resolution on the intermediate, decomposing the intermediate, and preparing the high-purity L-isopulegol by gel chromatography. The method has low cost of raw materials and low energy consumption of reaction, and is suitable for large-scale industrial production.
Description
Technical Field
The invention belongs to the technical field of crystallization separation, and particularly relates to a method for improving the optical purity of L-isopulegol through chiral resolution.
Background
Menthol is an important aromatic chemical, has a strong cooling effect, is widely applied to the fields of cosmetics, foods, beverages, medicines and the like, and is one of the most important synthetic flavors in industry.
Menthol has 8 isomers, which differ in their flavor properties: wherein the L-menthol has the strongest mint fragrance and the most obvious cooling effect, the racemic menthol has weaker cooling effect, and other isomers have no cooling effect.
In the process flow for synthesizing L-menthol, L-isopulegol is an important intermediate. The conventional method for the industrial preparation of L-isopulegol is the cyclization of citronellal under Lewis acid catalysis, but mixtures of L-isopulegol with its several isomers are usually obtained. Of these, most of the diastereoisomers of L-isopulegol can be removed by rectification, but the enantiomer D-isopulegol is difficult to separate out because of their close boiling points. The low optical purity is an important reason for restricting the use of L-isopulegol and L-menthol.
Patent CN101248032A discloses a process for the preparation of enriched L-isopulegol by melt crystallization. However, the process needs to be carried out under anhydrous and oxygen-free conditions, the conditions are severe, and in the crystallization process, the L-isopulegol and the enantiomer D-isopulegol thereof need to be crystallized out at first, and then the L-isopulegol is heated and melted to obtain the high-purity L-isopulegol, so that the steps are complicated, the requirements on equipment are high, and the cost for applying the process to industrial production is high.
Patent US5663460 discloses a process for purifying the optical purity of L-isopulegol by crystallization from petroleum ether or acetone at a temperature of-20 ℃ to-60 ℃. However, the process has strict requirements on temperature, consumes huge energy, does not induce crystallization by seed crystals, causes too wide metastable zone and too long crystallization time, influences experiment and production efficiency, has too low yield which is less than 10 percent, and is not suitable for industrial production.
Therefore, there is a need to develop an improved process that can improve the optical purity of L-isopulegol.
Disclosure of Invention
The invention aims to develop an improved method for improving the optical purity of L-isopulegol by chiral resolution aiming at the problems of low optical purity of L-isopulegol, low process yield of the existing crystallization separation scheme, harsh condition requirements and the like in the prior art. The method has low cost of raw materials and low energy consumption of reaction, and is suitable for large-scale industrial production.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for improving the optical purity of L-isopulegol by chiral resolution, comprising the steps of:
(1) reacting the D, L-isopulegol with a resolving agent L-linalool in a dispersing agent and an auxiliary agent, cooling, and performing centrifugal separation to obtain an intermediate L-isopulegol.L-linalool;
(2) and (3) carrying out alkali analysis on the intermediate to decompose the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography.
In the present invention, the D, L-isopulegol of step (1) is completely racemic or partially racemic.
In the invention, the mole ratio of the resolving agent L-linalool to the D, L-isopulegol in the step (1) is 0.5: 1-1.2: 1, preferably 0.8: 1-1: 1. L-linalool belongs to chain terpene alcohols, and has general characteristics of alcohols and olefin compounds, such as capability of dehydration reaction. Two C ═ C double bonds in the structure of the resolving agent can play a great role in promoting the reaction between the resolved substance D, L-isopulegol and the resolving agent L-linalool. The structure of the L-linalool contains a chiral center, and compared with the optical isomer D-linalool, the reaction activity of the L-linalool is higher.
In the invention, the auxiliary agent in the step (1) is sodium dodecyl sulfate, and the mass ratio of the sodium dodecyl sulfate to the D, L-isopulegol is 0.0001: 1-0.0010: 1. The sodium dodecyl sulfate is a typical anionic surfactant, has excellent wetting and penetrating effects, and simultaneously contains hydrophilic group sulfonic group and lipophilic group dodecyl group in the structure, and the asymmetry caused by the amphiphilic group can obviously change the interphase interfacial tension of the sodium dodecyl sulfate, so that the split D, L-isopulegol and the splitting agent L-linalool are combined more easily, the salt forming reaction rate is accelerated, and the kinetic splitting efficiency is improved.
In the invention, the dispersant in the step (1) is one or more of ethanol, n-propanol, isopropanol, ethyl acetate, propyl acetate, isopropyl acetate, acetonitrile and toluene, preferably ethyl acetate and/or toluene; the mass ratio of the dispersing agent to the D, L-isopulegol is 5: 1-20: 1, preferably 10: 1-15: 1.
In the invention, the reaction temperature in the step (1) is 70-80 ℃, the reaction time is 3-4 hours, and the temperature is cooled to 10-25 ℃.
In the invention, the resolving alkali in the step (2) is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate, preferably sodium bicarbonate and/or potassium bicarbonate, and is added in the form of aqueous solution.
In the invention, the pH adjusting end point of the alkali analysis in the step (2) is 6.5-7.5.
In the invention, the gel chromatography in the step (2) adopts gel permeation chromatography columns which are connected in series, the mobile phase is tetrahydrofuran, the flow rate is 0.5-2.0 mL/min, the time is 45min, and the temperature of the chromatography columns is 35-40 ℃. The gel chromatography is adopted to separate the high-purity L-isopulegol and the resolving agent L-linalool, so that the L-linalool can be recycled and reused, is beneficial to environmental protection, and meets the requirements of green chemical industry. According to chemical structure analysis, the structure of L-isopulegol contains 1 benzene ring, so that the molecular skeleton is small, L-linalool is polyhydric alcohol, the molecular skeleton is large, and the L-linalool and the linalool can sequentially pass through the inside and gaps of gel particles respectively when being separated by gel chromatography, so that different outflow rates are caused, and a good separation effect can be obtained.
In the invention, the total yield of the L-isopulegol product prepared by the chiral resolution method is 80-90.5%, and the optical purity is 99.0-99.9% e.e..
The chiral resolution method for preparing the L-isopulegol product has the positive effects that:
(1) the total yield of the L-isopulegol product prepared by the chiral resolution method can reach 80-90.5%, and the optical purity can reach 99.0-99.9% e.e.;
(2) the prices of the resolving agent, the dispersing agent, the auxiliary agent and the resolving alkali are all relatively low, so that the cost of raw materials is greatly reduced;
(3) the reaction conditions of the resolution reaction, the crystallization separation and the alkaline hydrolysis reaction are mild, the production energy consumption and the equipment cost are reduced, and the method is suitable for large-scale industrial production.
Drawings
FIG. 1 shows the results of gas chromatography detection of D, L-isopulegol before resolution in example 3;
FIG. 2 shows the results of gas chromatography for high purity L-isopulegol in example 3 after the resolution;
FIG. 3 shows the results of gas chromatography detection of high purity L-isopulegol after resolution in comparative example 1.
Detailed Description
The following examples are provided to further illustrate the technical solutions provided by the present invention, but the present invention is not limited to the listed examples, and includes any other known modifications within the scope of the claims of the present invention.
Information of main raw materials:
d, L-isopulegol, chemical purity of 99%, optical purity of 50% -99% e.e., pharmaceutical chemical limited of huge dragon hall of north of lake;
l-linalool with a chemical purity of 99% and an optical purity of 99% e.e., alatin reagent, ltd;
sodium dodecyl sulfate, chemical purity 99.5%, alatin reagent ltd;
ethanol, n-propanol, isopropanol, ethyl acetate, propyl acetate, isopropyl acetate, acetonitrile, toluene, chemical purity of 99%, alatin reagent limited;
sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, with a chemical purity of 99%, alatin reagent ltd.
Gel chromatography: series connection of chromatographic columns is adopted, the model is LC-20AD/RID-10A, the chromatographic columns are MZ-Gel SDplus 10E3A 5 mu m (8.0 multiplied by 300mm), MZ-Gel SDplus 500A 5 mu m (8.0 multiplied by 300mm), MZ-Gel SDplus 100A5 mu m (8.0 multiplied by 300mm), Shimadzu; mobile phase: tetrahydrofuran; flow rate: 0.5-2.0 mL/min; time: 45 min; temperature of the column: 35-40 ℃.
The characterization method of the L-isopulegol comprises the following steps: gas chromatograph: GC 2010-plus; chromatography column BETA-DEX-225; sample inlet temperature: 220 ℃; the split ratio is 50: 1; carrier gas flow: 30 ml/min; temperature rising procedure: maintaining at 95 deg.C for 35min, increasing to 200 deg.C at 20 deg.C/min, and maintaining for 5 min; detector temperature: at 300 ℃.
Example 1
15.4g (0.1mol) of D, L-isopulegol, 7.7g (0.05mol) of L-linalool, 0.003g of sodium dodecylsulfonate and 75g of ethanol were charged into a 200mL jacketed crystallization vessel, heated to 70 ℃ and reacted at that temperature with stirring for 3 hours. After the reaction is finished, slowly cooling to 10 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L aqueous solution of sodium hydroxide to adjust the pH value to 6.5, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 0.5mL/min, the time is 45min, and the temperature of the chromatography column is 35 ℃). The optical purity of the product was 99.0% e.e. and the total yield was 90.3% as determined by gas chromatography.
Example 2
15.4g (0.1mol) of D, L-isopulegol, 18.5g (0.12mol) of L-linalool, 0.015g of sodium dodecylsulfonate and 300g of isopropyl acetate were charged into a 500mL jacketed crystallization vessel, heated to 80 ℃ and reacted at that temperature with stirring for 4 hours. After the reaction is finished, slowly cooling to 25 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L sodium carbonate aqueous solution to adjust the pH value to 7.5, stirring for 4 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 2.0mL/min, the time is 45min, and the temperature of the chromatography column is 40 ℃). The optical purity of the product was 99.4% e.e. and the total yield was 81.2% as determined by gas chromatography.
Example 3
15.4g (0.1mol) of D, L-isopulegol, 12.3g (0.08mol) of L-linalool, 0.008g of sodium dodecylsulfonate and 150g of ethyl acetate were charged into a 500mL jacketed crystallization vessel, heated to 75 ℃ and reacted at that temperature with stirring for 3 hours. After the reaction is finished, slowly cooling to 15 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L aqueous solution of sodium bicarbonate to adjust the pH value to 6.8, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns in series connection, the mobile phase is tetrahydrofuran, the flow rate is 1.0mL/min, the time is 45min, and the temperature of the chromatography column is 40 ℃). The optical purity of the product was 99.8% e.e. and the total yield was 86.4% as determined by gas chromatography.
Example 4
15.4g (0.1mol) of D, L-isopulegol, 15.4g (0.1mol) of L-linalool, 0.005g of sodium dodecylsulfonate and 230g of toluene were charged into a 500mL jacketed crystallization vessel, heated to 75 ℃ and reacted at that temperature with stirring for 3 hours. After the reaction is finished, slowly cooling to 15 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L potassium bicarbonate aqueous solution to adjust the pH value to 7.1, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns in series connection, the mobile phase is tetrahydrofuran, the flow rate is 1.0mL/min, the time is 45min, and the temperature of the chromatography column is 35 ℃). The optical purity of the product was 99.9% e.e. and the total yield was 84.8% as determined by gas chromatography.
Example 5
15.4g (0.1mol) of D, L-isopulegol, 9.2g (0.06mol) of L-linalool, 0.004g of sodium dodecylsulfate and 120g of isopropanol were charged into a 200mL jacketed crystallization vessel, heated to 70 ℃ and reacted at that temperature with stirring for 3 hours. After the reaction is finished, slowly cooling to 10 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L potassium hydroxide aqueous solution to adjust the pH value to 7.0, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 1.5mL/min, the time is 45min, and the temperature of the chromatography column is 35 ℃). The optical purity of the product was 99.2% e.e. and the total yield was 88.5% as determined by gas chromatography.
Example 6
15.4g (0.1mol) of D, L-isopulegol, 15.4g (0.1mol) of L-linalool, 0.006g of sodium dodecylsulfonate and 180g of acetonitrile were charged into a 500mL jacketed crystallization vessel, heated to 80 ℃ and reacted at that temperature with stirring for 4 hours. After the reaction is finished, slowly cooling to 15 ℃, and obtaining an intermediate L-isopulegol.L-linalool through centrifugal separation.
Dissolving the intermediate L-isopulegol L-linalool in 100mL of water, adding 0.1mol/L potassium carbonate aqueous solution to adjust the pH value to 6.8, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 2.0mL/min, the time is 45min, and the temperature of the chromatography column is 35 ℃). The optical purity of the product was 99.6% e.e. and the total yield was 80.2% as determined by gas chromatography.
Comparative example 1
15.4g (0.1mol) of D, L-isopulegol, 15.0g (0.1mol) of L-tartaric acid and 150g of ethyl acetate were charged into a 500mL jacketed crystallization vessel, heated to 75 ℃ and reacted at that temperature with stirring for 3 hours. After the reaction is finished, slowly cooling to 15 ℃, and obtaining an intermediate L-isopulegol.L-tartaric acid through centrifugal separation.
Dissolving the intermediate L-isopulegol L-tartaric acid in 100mL of water, adding 0.1mol/L aqueous solution of sodium bicarbonate to adjust the pH value to 6.9, stirring for 3 hours, decomposing the intermediate, and obtaining the high-purity L-isopulegol by gel chromatography (adopting gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 1.0mL/min, the time is 45min, and the temperature of the chromatography column is 40 ℃). The optical purity of the product was 79.7% e.e. and the total yield was 75.2% as determined by gas chromatography.
Claims (12)
1. A method for improving the optical purity of L-isopulegol by chiral resolution, comprising the steps of:
(1) reacting the D, L-isopulegol with a resolving agent L-linalool in a dispersing agent and an auxiliary agent, cooling, and performing centrifugal separation to obtain an intermediate L-isopulegol.L-linalool;
(2) performing alkali analysis on the intermediate to decompose the intermediate, and performing gel chromatography to obtain high-purity L-isopulegol;
the auxiliary agent in the step (1) is sodium dodecyl sulfate;
the dispersing agent in the step (1) is one or more of ethanol, n-propanol, isopropanol, ethyl acetate, propyl acetate, isopropyl acetate, acetonitrile and toluene.
2. The process according to claim 1, wherein the D, L-isopulegol of step (1) is fully racemic or partially racemic.
3. The process according to claim 1 or 2, wherein the molar ratio of the resolving agent L-linalool to D, L-isopulegol in step (1) is 0.5:1 to 1.2: 1.
4. The method according to claim 3, wherein the molar ratio of the resolving agent L-linalool to D, L-isopulegol in step (1) is 0.8:1 to 1: 1.
5. The method according to claim 1 or 2, wherein the mass ratio of the auxiliary agent of step (1) to the D, L-isopulegol is 0.0001:1 to 0.0010: 1.
6. The method according to claim 1 or 2, wherein the dispersant of step (1) is one or both of ethyl acetate and toluene; the mass ratio of the dispersing agent to the D, L-isopulegol is 5: 1-20: 1.
7. The method according to claim 6, wherein the mass ratio of the dispersant to the D, L-isopulegol is 10:1 to 15: 1.
8. The method according to claim 1 or 2, wherein the reaction temperature in the step (1) is 70-80 ℃, the reaction time is 3-4 hours, and the temperature is cooled to 10-25 ℃.
9. The method of claim 1, wherein the resolving base of step (2) is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, and the resolving base is added in the form of an aqueous solution.
10. The method according to claim 9, wherein the resolving base of step (2) is one or both of sodium bicarbonate and potassium bicarbonate.
11. The method according to claim 1 or 9, wherein the pH adjustment endpoint of the alkali desorption in the step (2) is 6.5 to 7.5.
12. The method according to claim 1 or 9, wherein the gel chromatography of step (2) adopts gel permeation chromatography columns connected in series, the mobile phase is tetrahydrofuran, the flow rate is 0.5-2.0 mL/min, the time is 45min, and the temperature of the chromatography columns is 35-40 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811166606.7A CN109232184B (en) | 2018-10-08 | 2018-10-08 | Method for improving optical purity of L-isopulegol through chiral resolution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811166606.7A CN109232184B (en) | 2018-10-08 | 2018-10-08 | Method for improving optical purity of L-isopulegol through chiral resolution |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109232184A CN109232184A (en) | 2019-01-18 |
| CN109232184B true CN109232184B (en) | 2021-05-14 |
Family
ID=65055038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811166606.7A Active CN109232184B (en) | 2018-10-08 | 2018-10-08 | Method for improving optical purity of L-isopulegol through chiral resolution |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109232184B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232184B (en) * | 2018-10-08 | 2021-05-14 | 万华化学集团股份有限公司 | Method for improving optical purity of L-isopulegol through chiral resolution |
| CN110845305B (en) * | 2019-11-25 | 2022-06-28 | 安徽一帆香料有限公司 | Method for preparing L-menthol by adopting modified homogeneous catalyst |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101087746A (en) * | 2004-12-22 | 2007-12-12 | 巴斯福股份公司 | Method for the production of isopulegol |
| CN108484355A (en) * | 2018-04-13 | 2018-09-04 | 浙江新和成股份有限公司 | A kind of preparation method of isopulegol |
| CN109232184A (en) * | 2018-10-08 | 2019-01-18 | 万华化学集团股份有限公司 | A method of L- isopulegol optical purity is improved by chiral resolution |
-
2018
- 2018-10-08 CN CN201811166606.7A patent/CN109232184B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101087746A (en) * | 2004-12-22 | 2007-12-12 | 巴斯福股份公司 | Method for the production of isopulegol |
| CN108484355A (en) * | 2018-04-13 | 2018-09-04 | 浙江新和成股份有限公司 | A kind of preparation method of isopulegol |
| CN109232184A (en) * | 2018-10-08 | 2019-01-18 | 万华化学集团股份有限公司 | A method of L- isopulegol optical purity is improved by chiral resolution |
Non-Patent Citations (2)
| Title |
|---|
| 左旋异胡薄荷醇的催化合成;李锐;《香料香精化妆品》;20100430(第02期);第3页结论部分 * |
| 手性香料的不对称催化合成研究进展;樊超等;《应用技术学报》;20180930(第03期);第189-219页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109232184A (en) | 2019-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109232184B (en) | Method for improving optical purity of L-isopulegol through chiral resolution | |
| CN109761867B (en) | Vitamin D production by using lanolin as raw material3Is a new method for industrialization | |
| CN110467519B (en) | Ethynylation method | |
| CN108329194B (en) | Method for preparing isopulegol from citronellal and recovery method of catalyst of isopulegol | |
| US8404890B2 (en) | Production of 2,4-hexadienoic acid and 1,3-pentadiene from 6-methyl-5,6-dihydro-2-pyrone | |
| EP2079675A1 (en) | Process for the preparation of beta -ionones and vitamin a, vitamin a derivatives, carotenes and carotenoids | |
| CN103420979A (en) | Esomeprazole sodium refining method | |
| CN110845305B (en) | Method for preparing L-menthol by adopting modified homogeneous catalyst | |
| US20080207946A1 (en) | Process for preparation of highly pure isotretinoin | |
| CN113501752B (en) | Acid purification method of coenzyme Q10 | |
| CN113861034A (en) | Preparation method of 2-fluoro-3-nitrobenzoic acid | |
| CN103086852A (en) | Novel method for preparing 6,6-dimethylbicycol[3.1.1]heptane-2, 3-dione | |
| CN109134204B (en) | Synthesis method of intermediate 2-bromo-4-fluoro-5-chlorophenol | |
| CN109503447B (en) | A method for preparing cryptoxanthin from flos Tagetis Erectae extract | |
| CN102757367A (en) | Splitting process of racemic ethyl benzene sulfonic acid | |
| CN106588698A (en) | Preparation method of N-Boc biphenyl alaninal | |
| CN112778114A (en) | Efficient and environment-friendly method for synthesizing vitamin K1 | |
| CN107935858B (en) | Preparation method of 5-fluoro-2-nitrophenol | |
| CN109678738A (en) | A kind of method synthesizing (2S, 3S) -3- amino-two ring [2.2.2] octane -2- formic acid esters | |
| CN104529908A (en) | Method for preparing rosuvastatin calcium | |
| CN111253215B (en) | L-menthol recovery process method | |
| CN103910597B (en) | By the method for Deoxycholic Acid purified lycopene | |
| CN114315512B (en) | Synthesis method of alpha-terpineol | |
| CN111763193B (en) | Synthesis method of 1, 4-cyclohexanedione monoethylene glycol ketal | |
| CN109096047B (en) | Preparation method of (1R) -1, 3-diphenyl-1-propanol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |