A process for the preparation of D,L-menthyl benzoate

Abstract

The application provides a method for preparing D,L-menthyl benzoate, belongs to the field of organic chemical synthesis, uses a sodium methoxide / magnesium oxide type solid base catalyst instead of a strong acid catalyst and a sodium methoxide catalyst, does not corrode equipment, and the used solid base catalyst is convenient to separate and can be recycled; safe and low-toxicity solvents are used, a solvent reflux dropping process is adopted, a reversible reaction continuously proceeds in the direction of synthesizing menthyl benzoate, and the yield of menthyl benzoate is higher; compared with a traditional menthyl benzoate synthesis method, the sodium methoxide / magnesium oxide type solid base catalyst is a good catalyst for synthesizing menthyl benzoate, and the use of one or mixed solvents of solvents such as dichloromethane, cyclohexane, n-heptane and cyclooctane promotes the reaction, so that the yield of menthyl benzoate is higher, the synthesis process of the experiment is simple, and the method has high application value.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic chemical synthesis, and particularly relates to a method for preparing D,L-menthyl benzoate. BACKGROUND

[0002] Menthyl benzoate is a white transparent crystal with a faint cool mint flavor at room temperature, which is an important compound and can be used as a fixative in the daily chemical industry such as daily-use chemical fragrances, and can also be used as a solvent for oils, resins and the like; meanwhile, menthyl benzoate is an important intermediate in the synthesis of L-menthol and is a high-grade fragrance with broad prospects.

[0003] A classic synthesis method is to catalyze esterification of menthol and benzoic acid by using strong acidic substances such as sulfuric acid or p-toluenesulfonic acid to produce menthyl benzoate, or to use ester exchange reaction of benzoyl chloride and alcohol to synthesize. A patent with application number CN201210294449.9 discloses a synthesis method of menthyl benzoate, which uses p-toluenesulfonic acid to catalyze reaction of menthol and benzoic acid to synthesize menthyl benzoate, and after the reaction is completed, water washing, alkali washing, drying and the like processes are required, and a large amount of alkali-containing wastewater and waste solid are generated.

[0004] A patent with application number CN201510809332.9 discloses a synthesis process of L-menthol, which uses sodium methoxide and toluene, adopts a process of distillation during reaction, catalyzes menthol and methyl benzoate to synthesize menthyl benzoate, and uses toluene to carry out the generated methanol during the reaction to promote the ester exchange reaction, but as the solvent is distilled out, the sodium methoxide is easy to foam in the reactor, and the reaction reaches equilibrium earlier, resulting in unstable yield.

[0005] The existing technology uses strong acid substances as catalysts to catalyze esterification of benzoic acid and menthol, which not only corrodes the equipment, but also seriously pollutes the environment. The technology of using toluene as a solvent to distill during reaction, as the toluene is distilled out, the ability to carry methanol becomes weaker, resulting in low yield in the reversible ester exchange reaction. SUMMARY

[0006] In order to solve the above technical problems, the present application provides a method for preparing D,L-menthyl benzoate, which uses sodium methoxide / magnesium oxide type solid base as a catalyst, uses a solvent as a refluxing agent, adopts a process of dropping menthol, catalyzes ester exchange reaction of methyl benzoate and DL-menthol, and synthesizes menthyl benzoate. Under this process, the menthol is continuously added to the reaction system, which can make the reaction equilibrium right shift; and the solvent continuously refluxes in the reactor to continuously carry out the generated methanol, which promotes the reaction equilibrium right shift and the ester yield is higher; the sodium methoxide / solid base catalyst is not only simple to separate, but also can be recycled.

[0007] To achieve the above object, the present scheme first provides a method for preparing D, L-menthyl benzoate, comprising the following steps:

[0008] S1, methyl benzoate as a reaction substrate, first add sodium methoxide / magnesium oxide type solid base as catalyst, then add half the amount of solvent, menthol and the other half of the amount of solvent mixed by titration, the reaction is carried out in a heated reflux manner, the reaction system is naturally cooled to below 50℃ after the reaction is completed;

[0009] S2, the cooled system is filtered to remove the catalyst, and the filtered solution is distilled at normal pressure, and the solvent and the generated methanol are removed at a high temperature of 75-170℃, then the obtained crude product of menthyl benzoate is subjected to vacuum distillation, and the unreacted excess methyl benzoate and trace menthol are distilled off, and the fraction of 130℃-150℃ is collected as the product menthyl benzoate;

[0010] The preparation of the sodium methoxide / magnesium oxide type solid base catalyst comprises the following steps:

[0011] S101, take magnesium nitrate and dissolve it in deionized water to completely dissolve, slowly add ammonia water, stop adding when the pH value is 8, continue stirring after adding the ammonia water, filter and wash the obtained precipitate until the pH value is neutral, and separate the solid by filtration;

[0012] S102, dry the solid washed in step S101, calcine to obtain magnesium oxide, take 20% sodium methoxide in methanol solution, and soak the magnesium oxide for 24h;

[0013] S103, dry the soaked magnesium oxide in step S102 under vacuum, and finally calcine the sodium methoxide / magnesium oxide type solid base catalyst under the protection of inert gas.

[0014] As a preferred, the mass ratio of methyl benzoate to menthol in step S1 is 1-3:1.

[0015] As a preferred, the amount of catalyst used in step S1 is 1%~30% of the mass of menthol, and the mass of the half amount of solvent is 30-60% of the mass of menthol.

[0016] As a preferred, the solvent in step S1 is selected from any one or several of dichloromethane, cyclohexane, n-heptane, and cyclooctane.

[0017] As a preferred, the temperature of heating reflux in step S1 is 100℃-180℃, and the time of heating reflux is 2-10h.

[0018] As preferred, the solid-liquid ratio of magnesium nitrate and deionized water in the step S101 is 180g:1L, the concentration of ammonia water is 25%, and the stirring time is 2h.

[0019] As preferred, in the step S102, the drying temperature is 120 DEG C, and the time is 12h; the calcination temperature is 500 DEG C, and the time is 4h.

[0020] As preferred, in the step S103, the drying temperature is 100 DEG C, and the time is 12h; the calcination temperature is 300 DEG C, and the time is 2h.

[0021] The mechanism of the catalytic reaction of the scheme is as follows:

[0022] The sodium methoxide / magnesium oxide type solid base is used as the catalyst, the magnesium oxide is used as the carrier, the sodium methoxide is loaded on the magnesium oxide, and calcination is carried out, so that the sodium methoxide is prevented from being dissolved in the reaction liquid, solid-liquid separation and recycling are more convenient, the defect that sodium methoxide needs to be neutralized by acetic acid after each reaction is overcome, resource waste is reduced, and environmental pollution is reduced.

[0023] The solvent is used as a refluxing agent, the menthol is used for dropwise processing, the ester exchange reaction of methyl benzoate and DL-menthol is catalyzed, and menthol benzoate is synthesized. Under the process, the menthol is continuously added to the reaction system, the reaction equilibrium can be right shifted, the solvent is continuously refluxed in the reactor, the generated methanol is continuously taken out, the reaction equilibrium is right shifted, and the yield of the ester is higher. The sodium methoxide / solid base catalyst is not only simple to separate, but also can be recycled.

[0024] Compared with the prior art, the present application has the following beneficial effects:

[0025] (1) Compared with the traditional p-toluene sulfonic acid catalyzed synthesis method of menthol benzoate, the scheme does not need water washing, alkali washing and other procedures, does not produce wastewater, has small environmental pollution, does not corrode equipment, and compared with the synthesis method using sodium methoxide as a catalyst and methylbenzene as a solvent, the solid base catalyst is easier to separate and reuse, the refluxing use of one or mixed solvents of the solvents such as cyclohexane, n-heptane and cyclooctane promotes the reaction, the yield of menthol benzoate is higher, the solvent is common and easy to obtain, is easier to separate, is safer, and is more friendly to the environment. The synthesis process of the experiment is simple, and has high application value.

[0026] (2) The magnesium oxide is used as the carrier, the sodium methoxide is loaded on the magnesium oxide, and calcination is carried out, so that the sodium methoxide is prevented from being dissolved in the reaction liquid, solid-liquid separation and recycling are more convenient, the defect that sodium methoxide needs to be neutralized by acetic acid after each reaction is overcome, resource waste is reduced, and environmental pollution is reduced.

[0027] (3) The scheme adopts a reflux process of mixing and dropping one of the reaction substrates and the solvent, which can continuously make the reversible ester exchange equilibrium reaction proceed to the positive direction, and the yield of the menthyl benzoate is higher, and can reach more than 99%, and the preparation method is simple, the operation steps are less, the catalyst can be reused, and the production cost is low. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiment or prior art description. Obviously, the drawings in the following description are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0029] Figure 1 The chromatogram of the reaction product distribution of experimental example 1 is shown in the following figure.

[0030] Figure 2 The schematic diagram of the experimental device of experimental example 1 is shown in the following figure. DETAILED DESCRIPTION

[0031] In order to make the technical problems, technical solutions and advantages of the present application more clear, the following will be described in detail in combination with the drawings and specific embodiments.

[0032] The following examples are used to illustrate the present application, but not to limit the scope of the present application. Modifications or replacements of the methods, steps or conditions of the present application without departing from the spirit and essence of the present application all belong to the scope of the present application.

[0033] If not specifically indicated, the technical means used in the examples is the conventional means familiar to those skilled in the art; if not specifically indicated, the reagents used in the examples are commercially available.

[0034] Example 1: Preparation of sodium methoxide / magnesium oxide type solid base catalyst.

[0035] S1, 180 g of magnesium nitrate was dissolved in 1000 mL of deionized water to completely dissolve, and 25% concentration of ammonia water was slowly added dropwise, and the dropping was stopped when the pH value was 8; after the addition of ammonia water was completed, the stirring was continued for 2 h; the obtained precipitate was filtered, washed to neutral pH, and the solid was separated by filtration;

[0036] S2, the washed solid was dried at 120℃ for 12 h, and finally calcined at 500℃ for 4 h to prepare magnesium oxide;

[0037] S3, 100 g of 20% sodium methoxide methanol solution was taken, and the above magnesium oxide was soaked for 24 h; dried at 100℃ under vacuum for 12 h, and finally calcined at 300℃ under the protection of inert gas for 2 h to prepare sodium methoxide / magnesium oxide type solid base catalyst.

[0038] Experimental Example 1: Synthesis of D,L-benzoic acid menthyl ester.

[0039] S1. In a 500ml three-necked flask equipped with a magnetic stir bar, thermometer, constant pressure dropping funnel and reflux condenser with water separator, add 40.8g of methyl benzoate, 3.1g of sodium methoxide / magnesium oxide type solid base catalyst prepared in Example 1, and 15.6g of cyclohexane and n-heptane mixed solvent (1:1). Add a mixture of 31.2g of menthol and 15.6g of cyclohexane and n-heptane mixed solvent (1:1) to the constant pressure dropping funnel. Heat the reflux temperature to 110℃. When the target temperature is reached, start adding the mixture of menthol and solvent dropwise and start timing. React for 10 hours. After the reaction is completed, allow it to cool naturally to 40℃.

[0040] S2. Filter the cooled solution using a sintered glass funnel to separate the solid catalyst and obtain a clear liquid. Distill the solution under normal pressure to remove the reflux agent and methanol at 100°C. Distill the remaining crude menthyl benzoate under reduced pressure to remove unreacted methyl benzoate and menthol. Collect the fraction at 130°C as the product D,L-menthyl benzoate, with a yield of 99.05%.

[0041] The preparation mechanism is shown in the following formula:

[0042]

[0043] Figure 1 The chromatogram shows the distribution of the reaction products, from left to right: methanol, methyl benzoate, menthol, and menthyl benzoate. Using menthol as the base unit, according to the area normalization method, menthol accounts for approximately 0.95% and menthyl benzoate accounts for approximately 99.05%, resulting in a yield of 99.05% for menthyl benzoate.

[0044] Synthesis apparatus such as Figure 2 As shown, in Figure 2 The reaction apparatus is filled with reaction substrate, catalyst and solvent. After being heated to a certain temperature, the reactants undergo transesterification under the action of the catalyst. The product methanol and solvent azeotropically enter the condenser above the water separator for condensation. The condensed liquid mixture is separated by the water separator. The upper layer of solvent is refluxed into the round bottom flask, and the lower layer of methanol is continuously collected.

[0045] Experimental Example 2: Synthesis of D,L-benzoic acid menthyl ester.

[0046] S1, in a 500ml three-necked flask equipped with a magnetic stirrer, a thermometer, a constant pressure dropping funnel and a reflux condenser with a water separator, add methyl benzoate 78g, sodium methoxide / magnesium oxide type solid base 4.0g, cyclooctane 40g, in the constant pressure dropping funnel add a mixture of menthol 80g and cyclooctane 40g. Control the heating reflux temperature at 140°C, start dropping the mixture of menthol and solvent when the temperature reaches the target temperature and start timing, reaction for 6h, after the reaction is completed, cool down to 40°C naturally;

[0047] S2, filter the cooled solution with a sand core funnel, separate the solid catalyst, get a clear liquid, distill the solution under normal pressure, distill the refluxing agent and methanol at 110°C, distill the unreacted methyl benzoate and menthol from the remaining crude menthyl benzoate, collect the fraction at 150°C as the product D,L-menthyl benzoate, the yield is 98.8%.

[0048] Experimental Example 3 Synthesis of D,L-menthyl benzoate.

[0049] S1, in a 500ml three-necked flask equipped with a magnetic stirrer, a thermometer, a constant pressure dropping funnel and a reflux condenser with a water separator, add methyl benzoate 78g, sodium methoxide / magnesium oxide type solid base 4.0g, cyclooctane 40g, in the constant pressure dropping funnel add a mixture of menthol 80g and cyclooctane 40g. Control the heating reflux temperature at 140°C, start dropping the mixture of menthol and solvent when the temperature reaches the target temperature and start timing, reaction for 6h, after the reaction is completed, cool down to 40°C naturally;

[0050] S2, filter the cooled solution with a sand core funnel, separate the solid catalyst, get a clear liquid, distill the solution under normal pressure, distill the refluxing agent and methanol at 110°C, distill the unreacted methyl benzoate and menthol from the remaining crude menthyl benzoate, collect the fraction at 150°C as the product D,L-menthyl benzoate, the yield is 98.8%.

[0051] Experimental Example 3 Synthesis of D,L-menthyl benzoate.

[0052] S1, in a 500ml three-necked flask equipped with a magnetic stirrer, a thermometer, a constant pressure dropping funnel and a reflux condenser with a water separator, add methyl benzoate 78g, sodium methoxide / magnesium oxide type solid base 4.0g, cyclooctane 40g, in the constant pressure dropping funnel add a mixture of menthol 80g and cyclooctane 40g. Control the heating reflux temperature at 140°C, start dropping the mixture of menthol and solvent when the temperature reaches the target temperature and start timing, reaction for 6h, after the reaction is completed, cool down to 40°C naturally;

[0053] S2, the cooled solution was filtered with a sand core funnel to separate the solid catalyst, obtaining a clear liquid, the solution was subjected to atmospheric distillation, distilling off the refluxing agent and methanol at 75°C, the remaining crude menthyl benzoate was subjected to vacuum rectification, distilling off the unreacted methyl benzoate and menthol, collecting the fraction at 140°C as the product, with a yield of 97.6%.

[0054] Experimental Example 5 Synthesis of D,L-menthyl benzoate.

[0055] S1, in a 500ml three-necked flask equipped with a stirring magnet, a thermometer, a constant pressure dropping funnel and a reflux condenser with a water separator, 82g of methyl benzoate, 3.13g of sodium methoxide / magnesium oxide type solid base and 31.5g of cyclohexane were added, a mixture of 63g of menthol and 31.5g of cyclohexane was added to the constant pressure dropping funnel. The heating reflux temperature was controlled at 150°C, the mixture of menthol and solvent was added when the temperature reached the target temperature and the reaction time was started, the reaction was carried out for 2h, and then the reaction was naturally cooled to 40°C

[0056] S2, the cooled solution was filtered with a sand core funnel to separate the solid catalyst, obtaining a clear liquid, the solution was subjected to atmospheric distillation, distilling off the refluxing agent and methanol at 100°C, the remaining crude menthyl benzoate was subjected to vacuum rectification, distilling off the unreacted methyl benzoate and menthol, collecting the fraction at 130°C as the product, with a yield of 96.3%. D,L-menthyl benzoate was obtained.

[0057] Comparative Example 1 Preparation of D,L-menthyl benzoate using sodium methoxide as catalyst.

[0058] In a 500ml three-necked flask equipped with a stirring magnet, a thermometer and a spherical reflux condenser, D,L-menthol (31.2g), methyl benzoate (54.4g), 30% sodium methoxide (13g) and toluene 30 mL were added respectively, and stirred uniformly at room temperature, then the temperature of the reaction system was raised to 110°C, and the reaction was carried out by distillation, the first distilled materials were methanol and toluene in turn, then vacuum distillation was carried out, and the excess methyl benzoate, unreacted D,L-menthol and the product D,L-menthol benzoate were obtained in turn, with a yield of only 75%.

[0059] It can be seen that the yield of sodium methoxide as a catalyst alone is much lower than that of sodium methoxide / magnesium oxide type solid base catalyst, because the process of using sodium methoxide alone and distilling during the reaction will cause the toluene solvent to evaporate, and there will be only a small amount of solvent in the reactor at the later stage, which cannot smoothly carry out the generated methanol, leading to the reaction reaching equilibrium in advance, thus the yield is significantly reduced.

[0060] Experimental Example 6: Investigation of the characteristics of the sodium methoxide / magnesium oxide type solid base catalyst in the recycling process.

[0061] S1: The reaction mixture in Example 1 was filtered to separate the sodium methoxide / magnesium oxide type solid base catalyst, which was then added to a three-necked flask, and 40.8 g of methyl benzoate, 15.6 g of dichloromethane and 31.2 g of DL-menthol mixed with 15.6 g of refluxing agent dichloromethane were added. The reaction was heated to 110°C, and the mixture of menthol and solvent was added dropwise when the temperature reached the target temperature, and the reaction was allowed to proceed for 2 hours. After the reaction was completed, the solution was naturally cooled to 40°C.

[0062] S2: The cooled solution was filtered with a sand core funnel to separate the solid catalyst, and the clear liquid was obtained. The solution was subjected to atmospheric distillation, and the refluxing agent and methanol were distilled at 100°C. The remaining crude menthyl benzoate was subjected to vacuum distillation, and the unreacted methyl benzoate and menthol were distilled off. The product D, L-menthyl benzoate was collected at 130°C, and the yield was 98.1%.

[0063] The yield of each cycle of the catalyst recycling process is shown in Table 1 below. After 8 cycles, the yield of D, L-menthyl benzoate was still as high as 95.3%.

[0064]

[0065] The catalyst prepared by the above method is stable in recycling, and the yield of D, L-menthyl benzoate can reach 95.3% after 8 cycles, which is significantly better than the sodium methoxide catalyst alone.

[0066] The above description is only a preferred embodiment of the present application, and the protection scope of the present application is not limited to the above examples. Any improvement and modification obtained by those skilled in the art without departing from the technical concept of the present application should be considered as the protection scope of the present application.

Claims

1. A process for the preparation of D,L-menthyl benzoate, characterized in that, The method comprises the following steps: S1, methyl benzoate is used as a reaction substrate, sodium methoxide / magnesium oxide type solid base is used as a catalyst, half of the solvent is added, menthol and the other half of the solvent are mixed and added dropwise, and the reaction is carried out in a heating reflux mode, and the reaction system is naturally cooled to below 50 DEG C after the reaction is completed; S2, the cooled system is filtered to remove the catalyst, the filtered solution is distilled at normal pressure, the solvent and the generated methanol are removed at a high temperature of 75-170 DEG C, then the obtained crude product of menthyl benzoate is subjected to vacuum distillation, the unreacted excess methyl benzoate and a small amount of menthol are distilled off, and the product menthyl benzoate is collected by collecting the fraction at 130 DEG C-150 DEG C; The preparation of the sodium methoxide / magnesium oxide type solid base catalyst comprises the following steps: S101, magnesium nitrate is dissolved in deionized water, ammonia water is slowly added dropwise, the addition is stopped when the pH value is 8, the obtained precipitate is filtered and washed until the pH value is neutral, and the solid is separated by filtration; S102, the washed solid in step S101 is dried, calcined to obtain magnesium oxide, and 20% sodium methoxide methanol solution is used to soak the magnesium oxide for 24 h; S103, the soaked magnesium oxide in step S102 is dried under vacuum, and finally calcined under the protection of inert gas to obtain the sodium methoxide / magnesium oxide type solid base catalyst.

2. The production method according to claim 1, characterized by, The mass ratio of methyl benzoate to menthol in step S1 is 1-3:

1.

3. The preparation method according to claim 1, characterized in that, The amount of the catalyst in step S1 is 1%-30% of the mass of menthol, and the mass of the half amount of the solvent is 30-60% of the mass of menthol.

4. The production method according to claim 1, characterized by, The solvent in step S1 is selected from any one or several of dichloromethane, cyclohexane, n-heptane and cyclooctane.

5. The method of claim 1, wherein, The heating reflux temperature in step S1 is 100 DEG C-180 DEG C, and the heating reflux time is 2-10 h.

6. The method of claim 1, wherein, In step S101, the solid-liquid ratio of magnesium nitrate to deionized water is 180 g:1 L, the concentration of ammonia water is 25%, and the stirring time is 2 h.

7. The preparation method according to claim 1, characterized in that, In step S102, the drying temperature is 120 DEG C, and the time is 12 h; the calcination temperature is 500 DEG C, and the time is 4 h.

8. The method of claim 1, wherein, In step S103, the drying temperature is 100 DEG C, and the time is 12 h; the calcination temperature is 300 DEG C, and the time is 2 h.

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