阅读说明：本技术 一种乳酸薄荷酯的纯化方法 (Purification method of menthyl lactate ) 是由 杜阳吉 许锦雄 卫娜 于 2020-10-19 设计创作，主要内容包括：本发明公开了一种乳酸薄荷酯的纯化方法,包括以下步骤：(1)选取薄荷醇和乳酸直接酯化反应产生的包含乳酸薄荷酯的混合物,加入低极性烷烃,搅拌萃取；(2)用碱性饱和食盐水洗涤有机层至中性,静置分层,减压蒸干有机溶剂,得萃取浓缩物；(3)将萃取浓缩物溶于低级醇中配制成萃取物的醇溶液,然后上样至大孔树脂HP-20层析柱中,随后用不同浓度的低级醇进行梯度洗脱,GC检测洗脱液,将乳酸薄荷酯段合并浓缩并回收溶剂得到乳酸薄荷酯粗品；(4)将乳酸薄荷酯粗品溶于异丙醇的水溶液中,过滤,将上清液降温进行析晶、过滤,烘干即得纯化的乳酸薄荷酯。该纯化方法选择性高,高效,成本低,所得乳酸薄荷酯纯度高。(The invention discloses a menthyl lactate purification method, which comprises the following steps: (1) selecting a mixture containing menthyl lactate generated by direct esterification of menthol and lactic acid, adding low-polarity alkane, and stirring and extracting; (2) washing the organic layer with alkaline saturated salt solution to neutrality, standing for layering, and evaporating the organic solvent under reduced pressure to obtain an extraction concentrate; (3) dissolving the extract concentrate in lower alcohol to prepare an alcohol solution of an extract, then loading the alcohol solution into a macroporous resin HP-20 chromatographic column, then performing gradient elution by using lower alcohol with different concentrations, detecting eluent by GC, merging and concentrating menthyl lactate sections, and recovering a solvent to obtain a crude menthyl lactate product; (4) dissolving the menthyl lactate crude product in isopropanol water solution, filtering, cooling the supernatant, crystallizing, filtering, and oven drying to obtain purified menthyl lactate. The purification method has high selectivity, high efficiency, low cost and high purity of the obtained menthyl lactate.)

1. A method for purifying menthyl lactate is characterized by comprising the following steps:

(1) selecting a mixture containing menthyl lactate generated by direct esterification of menthol and lactic acid, adding low-polarity alkane, and stirring and extracting;

(2) washing the organic layer with alkaline saturated salt solution to neutrality, standing for layering, and evaporating the organic solvent under reduced pressure to obtain an extraction concentrate;

(3) dissolving the extract concentrate in lower alcohol to prepare an alcohol solution of an extract, then loading the alcohol solution into a macroporous resin HP-20 chromatographic column, then performing gradient elution by using lower alcohol with different concentrations, detecting eluent by GC, merging and concentrating menthyl lactate sections, and recovering a solvent to obtain a crude menthyl lactate product;

(4) dissolving the menthyl lactate crude product in isopropanol water solution, filtering, cooling the supernatant, crystallizing, filtering, and oven drying to obtain purified menthyl lactate.

2. The method for purifying menthyl lactate according to claim 1, characterized in that: the low-polarity alkane in the step (1) is n-hexane, cyclohexane or heptane, and the dosage relationship of the low-polarity alkane and the menthyl lactate reactant is 3-5 mL: 1g of the total weight of the composition.

3. The method for purifying menthyl lactate according to claim 1, characterized in that: and (2) adjusting the temperature to be 20-70 ℃ during stirring extraction in the step (1), and stirring extraction for 1-3 h.

4. The method for purifying menthyl lactate according to claim 1, characterized in that: in the step (2), the mass percentage of alkali in the alkaline saturated salt solution is 2-5%, and the dosage of the alkaline saturated salt solution is 2-4 times of the total mass of the organic layer; the alkali is sodium hydroxide, potassium hydroxide or sodium carbonate.

5. The method for purifying menthyl lactate according to claim 1, characterized in that: the lower alcohol in the step (3) is methanol, ethanol or isopropanol, and the mass percentage of the extract in the alcoholic solution of the extract is 15-30%.

6. The method for purifying menthyl lactate according to claim 1, characterized in that: and (4) in the step (3), the loading capacity of the macroporous resin HP-20 is 3-6 times of the total mass of the extraction concentrate.

7. The method for purifying menthyl lactate according to claim 1, characterized in that: when the lower alcohols with different concentrations are used for gradient elution in the step (3), the volume percentage of the lower alcohols is respectively 15-25%, 35-45%, 55-65%, 75-85% and 90% -anhydrous lower alcohols.

8. The method for purifying menthyl lactate according to claim 1, characterized in that: and (4) when the elution liquid is detected by GC in the step (3), selecting elution liquid with the menthyl lactate mass percentage content higher than 90% and combining the elution liquid.

9. The method for purifying menthyl lactate according to claim 1, characterized in that: in the step (4), the mass percentage of the isopropanol in the isopropanol aqueous solution is 92-96%, and the amount of the isopropanol aqueous solution is 30-50% of the mass percentage of the menthyl lactate crude product.

10. The method for purifying menthyl lactate according to claim 1, characterized in that: the temperature during crystallization in the step (4) is-10-0 ℃, and the time is 14-24 h; the mass percentage of the purified menthyl lactate is higher than 98%.

Technical Field

The invention belongs to the technical field of menthyl lactate, and particularly relates to a menthyl lactate purification method.

Background

Menthyl Lactate (ML) is prepared by two main methods: the method is an ester exchange method taking ethyl lactate and menthol as raw materials, and the yield is low; the other is a direct esterification method which takes menthol and lactic acid as raw materials. The direct esterification method is the main method for industrially producing menthyl lactate at present, but the product menthyl lactate still contains hydroxyl groups and can be continuously reacted with lactic acid in a system to form "di-polyester" or "poly-ester" in the esterification process, and the process is as follows:

meanwhile, under the condition of acid catalysis, the lactic acid can generate side reactions such as intramolecular self-polymerization and alkene formation by alcohol dehydration. The side reactions lead to complex subsequent product components, especially the chemical properties of the dimers and the polymers are similar, and great difficulty is brought to subsequent purification.

In published reported patents, for example, U.S. patent No. 7173146 teaches esterification of menthol and menthyl lactate in a suitable solvent with a catalyst to obtain menthyl lactate and its dimers and trimers. The mixture obtained is subjected to strong base hydrolysis such as sodium hydroxide to degrade the dimers and polymers thereof, so as to selectively hydrolyze the dimers and polymers to menthyl lactate, but in practice, a large amount of menthyl lactate is hydrolyzed during the hydrolysis process and converted into sodium lactate and menthol as raw materials. Chinese patent CN101456812A also teaches a method for purifying menthyl lactate by dissolving menthyl lactate containing dimers, i.e. polymers, in a lower alcohol, performing a transesterification reaction under alkaline conditions in order to convert the dimers or polymers to menthyl lactate, and subsequently further purifying the product by distillation or recrystallization. The above-mentioned methods, either hydrolysis or alcoholysis, have the disadvantages of low selectivity, low cost, low efficiency, etc.

Disclosure of Invention

The invention aims to provide a menthyl lactate purification method which is high in selectivity, high in efficiency, low in cost and high in purity of the obtained menthyl lactate.

The above object of the present invention is achieved by the following technical solutions: a method for purifying menthyl lactate comprising the steps of:

(1) selecting a mixture containing menthyl lactate generated by direct esterification of menthol and lactic acid, adding low-polarity alkane, and stirring and extracting;

(2) washing the organic layer with alkaline saturated salt solution to neutrality, standing for layering, and evaporating the organic solvent under reduced pressure to obtain an extraction concentrate;

(3) dissolving the extract concentrate in lower alcohol to prepare an alcohol solution of an extract, then loading the alcohol solution into a macroporous resin HP-20 chromatographic column, then performing gradient elution by using lower alcohol with different concentrations, detecting eluent by GC, merging and concentrating menthyl lactate sections, and recovering a solvent to obtain a crude menthyl lactate product;

(4) dissolving the menthyl lactate crude product in isopropanol water solution, filtering, cooling the supernatant, crystallizing, filtering, and oven drying to obtain purified menthyl lactate.

In the above method for purifying menthyl lactate:

preferably, the mixture containing menthyl lactate in step (1) can be prepared by a conventional direct esterification method using menthol and lactic acid as raw materials.

It is recommended that menthyl lactate mixtures be prepared with reference to the following references: zhengheptuii, Wangkufen, Zhang Jing, etc. the synthesis and application of menthyl lactate [ J ]. Shandong chemical engineering, 1994, (1) 7-8.

Preferably, the low-polarity alkane in the step (1) is n-hexane, cyclohexane or heptane, and the dosage relationship between the low-polarity alkane and the menthyl lactate reactant is 3-5 mL: 1g of the total weight of the composition.

The technical scheme in the application adopts a direct esterification method, does not relate to hydrolysis of by-products such as dimer and the like, and adopts low-polarity alkane extraction to finish primary enrichment of menthyl lactate.

Preferably, the temperature is adjusted to 20-70 ℃ during stirring extraction in the step (1), and stirring extraction is carried out for 1-3 hours.

Preferably, the temperature is adjusted to 30-70 ℃ during stirring and extraction in the step (1), and stirring and extraction are carried out for 1-3 hours.

Excessive temperature during extraction will extract more impurities, and too low a temperature will result in reduced solubility of menthyl lactate.

Preferably, in the step (2), the mass percentage of alkali in the alkaline saturated common salt water is 2-5%, and the dosage of the alkaline saturated common salt water is 2-4 times of the total mass of the organic layer; the alkali is sodium hydroxide, potassium hydroxide or sodium carbonate.

Here, the organic layer is washed with a basic saturated brine in order to wash small amounts of acidic impurities such as lactic acid and p-toluenesulfonic acid, the concentration of the base should not be too high, which would hydrolyze the target product menthyl lactate.

Preferably, the lower alcohol in the step (3) is methanol, ethanol or isopropanol, and the mass percentage of the extract in the alcoholic solution of the extract is 15-30%.

The lower alcohol is used here not only for dissolving the target substance but more importantly also for chromatographic elution to obtain the initial eluent, unlike the alcoholysis carried out in the background art as a solution alone for dissolving menthyl lactate. Preferably, the loading amount of the macroporous resin HP-20 in the step (3) is 3-6 times of the total mass of the extraction concentrate.

Preferably, when the lower alcohols with different concentrations are used for gradient elution in the step (3), the volume percentage of the lower alcohols is 15-25%, 35-45%, 55-65%, 75-85% and 90% -anhydrous lower alcohols respectively.

More preferably, when the gradient elution is performed by using lower alcohols with different concentrations in step (3), the volume percentages of the lower alcohols are 20%, 40%, 60%, 80% and anhydrous lower alcohols, respectively.

Preferably, when the elution solution is detected by GC in the step (3), the elution solutions with the menthyl lactate content higher than 90 percent by mass are selected and combined.

When GC is used for detecting the eluent, the detection method can be carried out according to the method of national standard GB 28338-2012.

Preferably, in the step (4), the mass percentage of the isopropanol in the isopropanol aqueous solution is 92-96%, and the amount of the isopropanol aqueous solution is 30-50% of the mass percentage of the menthyl lactate crude product.

The target may be recrystallized from isopropanol.

Preferably, the temperature during the crystallization in the step (4) is-10-0 ℃, and the time is 14-24 hours; the mass percentage of the purified menthyl lactate is higher than 98%.

The invention has the following advantages:

(1) the purification method of menthyl lactate has the advantages of concise overall process, mild conditions, lower overall cost and easy realization of industrialization, and the prepared menthyl lactate has the content of more than 98 percent and higher purity;

(2) in the preparation method of menthyl lactate, the raw materials are firstly purified in advance and then resin adsorption and purification are carried out, the process is simple, the product enrichment capacity is high, the energy consumption is low, the raw materials are nontoxic, the resin can be regenerated and recycled, and the industrial production is easy to realize.

Detailed Description

The present invention will be further described with reference to specific embodiments, but the scope of the invention as claimed is not limited to the following embodiments.

Example 1

Taking menthyl lactate reactant (mixture containing higher lactoyl ester of menthyl lactate, 100g, ML 85%, mass percentage, preparation method referring to the above literature, or directly purchasing a commercial product), adding 300mL heptane, and extracting at 70 deg.C for 3h under stirring;

then 600 ml of alkaline saturated salt water with 2% sodium hydroxide concentration is used for washing the organic layer to be neutral, standing, layering, decompressing and evaporating the organic solvent to dryness, and about 95g of extraction concentrate is obtained;

dissolving the concentrate in methanol to prepare a methanol solution with the concentration of 15% (mass percentage content of the concentrate), then loading the alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 285g of the concentrate, then carrying out gradient elution by using methanol solutions with the concentrations of 20%, 40%, 60%, 80% and 100% (anhydrous methanol), detecting eluent by GC (the detection method is GB28338-2012), merging eluent with the menthyl lactate content higher than 90% (usually in the eluent with the content of more than 80%) and concentrating and recovering a solvent to obtain a crude product of 85g and ML 92;

dissolving the crude product in 92% isopropanol/water solution to prepare 30% isopropanol solution, filtering, cooling clear liquid to-10 deg.C for crystallization, adding seed crystal, maintaining for 14 hr, filtering, and oven drying filter residue to obtain product 78g with purity of 98.5% (according to national standard GB28338-2012, the same below).

Example 2

Taking a mixture of menthol and lactic acid directly esterified to produce higher lactoyl esters comprising one or more menthyl lactates, (100g, ML 85%, preparation method refer to literature above) adding 500ML n-hexane and extracting at 30 deg.c for 1h with stirring;

then 2000mL of alkaline saturated salt water with 3% (mass percentage content) potassium hydroxide concentration is used for washing the organic layer to neutrality, standing, layering, decompressing and evaporating the organic solvent to dryness, and about 94g of extraction concentrate is obtained;

dissolving the concentrate in ethanol to prepare an ethanol solution with the concentration of 30%, then loading an alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 475g of the concentrate, then carrying out gradient elution by using ethanol solutions with the concentrations of 20%, 40%, 60%, 80% and 100% (absolute ethanol), detecting the eluent by GC, combining the eluents with the menthyl lactate content higher than 90%, concentrating and recovering a solvent to obtain a crude product 86g, ML 93%;

dissolving the crude product in 96% isopropanol/water solution to prepare 50% isopropanol solution, filtering, cooling the clear solution to-5 deg.C for crystallization, adding seed crystal, maintaining for 18 hr, filtering, and oven drying the filter residue to obtain 79g product with purity of 98.6%.

Example 3

Taking a mixture of menthol and lactic acid directly esterified to produce a higher lactoyl ester comprising one or more menthyl lactates, (100g, ML 85%, source as in example 1) adding 400ML cyclohexane and extracting with stirring at 70 ℃ for 3 h;

then 1200mL of alkaline saturated saline solution with 5% sodium carbonate concentration is used for washing the organic layer to be neutral, standing, layering, decompressing and evaporating the organic solvent to dryness to obtain about 93g of extraction concentrate;

dissolving the concentrate in isopropanol to prepare 15% isopropanol solution, loading the alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 285g of concentrate, performing gradient elution by using 20%, 40%, 60%, 80% and 100% (anhydrous isopropanol) isopropanol solution, detecting the eluent by GC, combining the eluates with menthyl lactate content higher than 90%, concentrating and recovering the solvent to obtain crude products 87g and ML 95%;

dissolving the crude product in 92% isopropanol/water solution to prepare 30% isopropanol solution, filtering, cooling the clear solution to 0 deg.C for crystallization, adding seed crystal, maintaining for 24 hr, filtering, and oven drying the filter residue to obtain 77g product with purity of 98.9%.

Example 4

Taking a mixture comprising one or more higher lactoyl esters of menthyl lactate produced by direct esterification of menthol and lactic acid, (100g, ML 85%, source as in example 1) adding 350ML cyclohexane and extracting with stirring at 70 ℃ for 3 h;

then 1050mL of alkaline saturated saline solution with 5% sodium hydroxide concentration is used for washing the organic layer to be neutral, standing, layering, decompressing and evaporating the organic solvent to dryness, and about 95g of extraction concentrate is obtained;

dissolving the concentrate in methanol to prepare a methanol solution with the concentration of 20%, then loading an alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 285g of the concentrate, then carrying out gradient elution by using methanol solutions with the concentrations of 20%, 40%, 60%, 80% and 100% (anhydrous methanol), detecting the eluent by GC, combining the eluents with the menthyl lactate content higher than 90%, concentrating and recovering a solvent to obtain a crude product of 88g and ML 93%;

dissolving the crude product in 95% isopropanol/water solution to obtain 40% isopropanol solution, filtering, cooling the clear solution to 0 deg.C for crystallization, adding seed crystal, maintaining for 20 hr, filtering, and oven drying the filter residue to obtain 76g product with purity of 98.5%.

Example 5

Taking a mixture of menthol and lactic acid directly esterified to produce higher lactoyl ester containing one or more menthyl lactate, (100g, ML 85%, source same as example 1) adding 350mL of n-hexane and extracting at 70 deg.C for 3h with stirring;

then 1050mL of alkaline saturated saline solution with 5% potassium hydroxide concentration is used for washing the organic layer to be neutral, standing, layering, decompressing and evaporating the organic solvent to dryness, and about 96g of extraction concentrate is obtained;

dissolving the concentrate in isopropanol to prepare an isopropanol solution with the concentration of 25%, then loading an alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 285g of the concentrate, then carrying out gradient elution by using an isopropanol solution with the concentration of 20%, 40%, 60%, 80% and 100% (anhydrous isopropanol), detecting the eluent by GC, combining the eluents with the menthyl lactate content higher than 90%, concentrating and recovering a solvent to obtain 89g of crude product, ML 94%;

dissolving the crude product in 94% isopropanol/water solution to prepare 40% isopropanol solution, filtering, cooling the clear solution to 0 deg.C for crystallization, adding seed crystal, maintaining for 18 hr, filtering, and oven drying the filter residue to obtain 80g product with purity of 98.4%.

Example 6

Taking a mixture of menthol and lactic acid directly esterified to produce higher lactoyl esters containing one or more menthyl lactates, (100g, ML 85%, source same as example 1) adding 350mL of n-hexane and extracting with stirring at 50 deg.C for 2 h;

then 1050mL of alkaline saturated saline solution with 4% sodium carbonate concentration is used for washing the organic layer to be neutral, standing, layering, decompressing and evaporating the organic solvent to dryness, and about 92.5g of extract concentrate is obtained;

dissolving the concentrate in isopropanol to prepare an isopropanol solution with the concentration of 20%, then loading an alcohol solution into a macroporous resin HP-20 chromatographic column loaded with 285g of the concentrate, then carrying out gradient elution by using an isopropanol solution with the concentration of 20%, 40%, 60%, 80% and 100% (anhydrous isopropanol), detecting the eluent by GC, combining the eluents with the menthyl lactate content higher than 90%, concentrating and recovering a solvent to obtain a crude product 86g, ML 93%;

dissolving the crude product in 94% isopropanol/water solution to prepare 40% isopropanol solution, filtering, cooling the clear solution to 0 deg.C for crystallization, adding seed crystal, maintaining for 18 hr, filtering, and oven drying the filter residue to obtain 79g product with purity of 98.6%.

The present invention has been described above by referring to a part of specific embodiments, and it should be noted that the above-mentioned specific embodiments are only used for further description of the present invention and do not represent a limitation to the scope of the present invention. Other insubstantial modifications and adaptations of the present invention can be made without departing from the scope of the present invention.