Continuous flow preparation method of menthecarboxylic acid
By using a dynamic tubular reactor for continuous flow reaction, the problem of low efficiency in batch reaction was solved, enabling the efficient preparation of high-purity menthol formic acid and improving raw material utilization and product consistency.
Patent Information
- Application Number
- CN202511738858.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-25
- Publication Date
- 2026-02-27
AI Technical Summary
Traditional batch reactor processes have low reaction efficiency and low raw material utilization, resulting in unstable quality of menthol formic acid products.
A dynamic tubular reactor was used for continuous flow reaction. Temperature, pressure, feed rate and gas inlet rate were set to realize the continuous carboxylation reaction of menthol Grignard reagent with CO2. Post-processing yielded pure menthol formic acid.
The reaction time is shortened to the minute level, the Grignard reagent conversion rate reaches over 98%, the menthol formic acid yield reaches over 80%, the product purity is as high as 95%, the batch consistency is good, the degree of automation is high, and the emission of waste is reduced.
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Figure CN121574047A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of fine chemical technology, in particular to a continuous flow preparation method of menthofolic acid. BACKGROUND
[0002] As an important intermediate, menthofolic acid is widely used in medicine, food, tobacco and daily chemical products. Due to its ability to impart a cool, fresh feeling, it has a refreshing and brain-awakening effect, and is an indispensable additive in people's daily life. With the increasing demand for natural cool products, the demand for high-quality menthofolic acid is also increasing.
[0003] Traditional menthofolic acid preparation methods usually use kettle reactions, the most common of which is the preparation by reacting menthyl Grignard reagent with carbon dioxide; however, the existing kettle reaction process has low reaction efficiency and low raw material utilization rate, resulting in unstable product quality in different batches.
[0004] In view of the above defects, the present inventors have finally obtained the present application after long-term research and practice. SUMMARY
[0005] To solve the above technical defects, the technical solution adopted by the present application provides a continuous flow preparation method of menthofolic acid, comprising the following steps: S1, preparing menthyl Grignard reagent under argon protection; S2, heating the dynamic tubular reactor to the reaction temperature using a high-low temperature all-in-one machine, and setting the rotation speed of the dynamic tubular reactor and the reaction pressure in the dynamic tubular reactor; S3, feeding the menthyl Grignard reagent and CO2 into the dynamic tubular reactor for continuous carboxylation reaction, and setting the feeding speed of the menthyl Grignard reagent, the residence time in the dynamic tubular reactor, and the feeding speed of CO2; S4, obtaining the reaction product after the reaction in the dynamic tubular reactor is completed, acidifying and separating the reaction product to obtain menthofolic acid crude product, and then obtaining menthofolic acid pure product after post-treatment.
[0006] Preferably, in the step S2, the reaction temperature is set to 70-120℃.
[0007] Preferably, in the step S2, the reaction temperature is set to 90℃.
[0008] Preferably, in the step S2, the reaction pressure is set to 0.2-1.5 MPa.
[0009] Preferably, in the step S2, the reaction pressure is set to 1 MPa.
[0010] Preferably, in the step S3, the residence time is set to 5-15 min.
[0011] Preferably, in the step S3, the residence time is set to 10 min.
[0012] Preferably, in the step S3, the feeding speed of the menthyl Grignard reagent is set to 10-30 mL / min.
[0013] Preferably, in the step S3, the feeding speed of the CO2 is set to 0.5-1.8 L / min.
[0014] Preferably, in the step S3, the ratio of the feeding speed of the menthyl Grignard reagent to the feeding speed of the CO2 is set to 18:1000-20:1000.
[0015] Compared with the prior art, the present application has the beneficial effects that the present application adopts the dynamic tubular reactor to perform the continuous flow reaction at the set temperature, shortens the several hours required by the traditional kettle type reaction to the minute level, the total reaction time from the Grignard reagent to the carboxylation reaction is not more than 15 min, and the conversion rate of the Grignard reagent can reach more than 98%, and the yield of menthyl formate can reach more than 80%. BRIEF DESCRIPTION OF DRAWINGS
[0016] Figure 1 is a synthetic flow chart of the continuous flow preparation method of the menthyl formate; Figure 2 is an equipment connection schematic diagram of the continuous flow preparation method of the menthyl formate.
[0017] The numbers in the figure represent: 1-Grignard reagent raw material storage tank; 2-plunger pump; 3-dynamic tubular reactor; 4-high-low temperature all-in-one machine; 5-CO2 bottle; 6-menthyl formate acidification tank. DETAILED DESCRIPTION
[0018] The above and other technical features and advantages of the present application will be described in more detail below in conjunction with the accompanying drawings.
[0019] As shown in Figure 1 and Figure 2 , the synthetic flow chart of the continuous flow preparation method of the menthyl formate is shown in Figure 1 , and the equipment connection schematic diagram of the continuous flow preparation method of the menthyl formate is shown in Figure 2 .
[0020] The continuous flow preparation method of the menthyl formate of the present application comprises the steps of: S1, preparing the menthyl Grignard reagent under the condition of argon protection; S2, a high and low temperature integrated machine 4 is used to heat the dynamic tubular reactor 3 to the reaction temperature, and the rotation speed of the dynamic tubular reactor 3 and the reaction pressure inside the dynamic tubular reactor 3 are set. S3, the Grignard reagent raw material storage tank 1 containing the menthol Grignard reagent is connected to the liquid inlet of the dynamic tubular reactor 3 via a plunger pump 2, and the feed rate of the menthol Grignard reagent and the residence time in the dynamic tubular reactor 3 are set; the CO2 bottle 5 is connected to the gas inlet of the dynamic tubular reactor 3 via a feed valve, and the CO2 inlet rate is set to realize the continuous carboxylation reaction of the menthol Grignard reagent and CO2. S4. After the reaction in the dynamic tubular reactor 3 is completed, the reaction product flows out through the outlet of the dynamic tubular reactor 3 to the menthol formic acid acidification tank 6. The reaction product is acidified and separated to obtain crude menthol formic acid, which is then post-processed to obtain pure menthol formic acid.
[0021] Preferably, in step S2, the reaction temperature is set to 70°C to 120°C.
[0022] Preferably, in step S2, the reaction temperature is set to 90°C.
[0023] Preferably, in step S2, the reaction pressure is set to 0.2 MPa to 1.5 MPa.
[0024] Preferably, in step S2, the reaction pressure is set to 1 MPa.
[0025] Preferably, in step S3, the dwell time is set to 5 min to 15 min.
[0026] Preferably, in step S3, the dwell time is set to 10 minutes.
[0027] Preferably, in step S3, the feed rate of the menthol Gigermann reagent is set to 10 mL / min to 30 mL / min.
[0028] Preferably, in step S3, the CO2 intake rate is set to 0.5 L / min to 1.8 L / min.
[0029] Preferably, in step S3, the ratio of the feed rate of the menthol Gigermann reagent to the inlet rate of the CO2 is set to 18:1000 to 20:1000.
[0030] The present invention uses the dynamic tubular reactor 3 to carry out a continuous flow reaction at a set temperature, which shortens the hours required for traditional batch reaction to the minute level. The total reaction time from Grignard reagent to carboxylation reaction completion does not exceed 15 minutes, and the conversion rate of Grignard reagent can reach more than 98%, and the yield of menthol formic acid can reach more than 80%.
[0031] This invention utilizes continuous flow microreaction technology, which ensures that only a very small amount of reactive intermediates exist in the preparation system, fundamentally eliminating the risk of large amounts of Grignard reagents accumulating in traditional batch reactions. Furthermore, the microchannels in the dynamic tubular reactor 3 have highly efficient heat transfer characteristics, which can remove the heat of reaction in a timely manner and avoid temperature runaway.
[0032] In the dynamic tubular reactor 3, carbon dioxide is fully contacted with Grignard reagents, which greatly improves mass transfer efficiency and carbon dioxide utilization rate can reach more than 90%, reducing raw material costs. The continuous flow process parameters are precisely controllable, the product purity is as high as 95% or more, the batch consistency is significantly better than traditional methods, and the degree of automation is high, energy consumption is reduced, carbon dioxide utilization rate is high, and the emission of waste gas, wastewater, and solid waste is reduced, which meets the requirements of green chemical industry.
[0033] Comparative example (traditional autoclave process) The menthol-based magnesium chloride solution was cooled to room temperature, and CO2 was slowly introduced. The temperature was controlled below 30°C during the reaction. The Grignard reagent content was measured during the aeration process. The total aeration time was 4 hours, after which the aeration was stopped. After acidification with 10% dilute sulfuric acid, the purity of menthol formic acid was 95.6%, the Grignard reagent conversion rate was 68%, the CO2 utilization rate was only 38%, and the total yield of menthol formic acid was 58.7%. Example 1
[0034] At 90℃, the feed rate of the menthol Grignard reagent was 30 mL / min, the residence time was 5 min, the CO2 gas flow rate was 1.57 L / min, and the purity of menthol formic acid after acidification with 10% dilute sulfuric acid was 97.3%, the conversion rate of Grignard reagent was 98%, and the total yield of menthol formic acid was 68.7%. Example 2
[0035] At 90℃, the feed rate of the menthol Grignard reagent was 20 mL / min, the residence time was 7.5 min, the CO2 gas flow rate was 1.05 L / min, and the purity of menthol formic acid after acidification with 10% dilute sulfuric acid was 97.4%, the conversion rate of Grignard reagent was 98%, and the total yield of menthol formic acid was 74.8%. Example 3
[0036] At 90℃, the feed rate of the menthol Grignard reagent was 10 mL / min, the residence time was 15 min, the CO2 gas flow rate was 0.53 L / min, and the purity of menthol formic acid after acidification with 10% dilute sulfuric acid was 92.6%, the conversion rate of Grignard reagent was 98%, and the total yield of menthol formic acid was 82%. Example 4
[0037] At 90℃, the feed rate of the menthol Grignard reagent was 20 mL / min, the residence time was 7.5 min, the CO2 gas flow rate was 1.05 L / min, and the purity of menthol formic acid after acidification with 10% dilute sulfuric acid was 98.2%, the conversion rate of Grignard reagent was 98%, and the total yield of menthol formic acid was 78.6%.
[0038] The above description is merely a preferred embodiment of the present invention and is illustrative rather than restrictive. Those skilled in the art will understand that many changes, modifications, and even equivalents can be made within the spirit and scope defined by the claims of the present invention, all of which will fall within the protection scope of the present invention.
Claims
1. A continuous flow preparation method for mentholic acid, characterized in that, Including the following steps: S1, peppermint Gibberellic reagent was prepared under argon protection; S2, a high and low temperature integrated machine is used to heat the dynamic tubular reactor to the reaction temperature, and the rotation speed of the dynamic tubular reactor and the reaction pressure inside the dynamic tubular reactor are set. S3, the peppermint Girdle reagent and CO2 are introduced into the dynamic tubular reactor for continuous carboxylation reaction, and the feed rate of the peppermint Girdle reagent, the residence time in the dynamic tubular reactor, and the inlet rate of CO2 are set. S4. After the reaction in the dynamic tubular reactor is completed, the reaction product is obtained. The reaction product is acidified and separated to obtain crude menthol formic acid. After further processing, pure menthol formic acid is obtained.
2. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S2, the reaction temperature is set to 70℃~120℃.
3. The continuous flow preparation method of menthol as described in claim 1, characterized in that, In step S2, the reaction temperature is set to 90°C.
4. The continuous flow preparation method of menthol as described in claim 1, characterized in that, In step S2, the reaction pressure is set to 0.2 MPa to 1.5 MPa.
5. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S2, the reaction pressure is set to 1 MPa.
6. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S3, the dwell time is set to 5 min to 15 min.
7. The continuous flow preparation method of menthol as described in claim 1, characterized in that, In step S3, the dwell time is set to 10 minutes.
8. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S3, the feed rate of the peppermint Gigermann reagent is set to 10 mL / min to 30 mL / min.
9. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S3, the CO2 intake rate is set to 0.5 L / min to 1.8 L / min.
10. The continuous flow preparation method of menthol formic acid as described in claim 1, characterized in that, In step S3, the ratio of the feed rate of the menthol Gigermann reagent to the inlet rate of the CO2 is set to 18:1000 to 20:1000.