Method for preparing D, L-menthyl benzoate

Abstract

The invention provides a method for preparing D, L-menthyl benzoate, and belongs to the field of organic chemical synthesis, a sodium methoxide / magnesium oxide type solid base catalyst is used for replacing strong acid and sodium methoxide catalysts, equipment is not corroded, and the used solid base catalyst is convenient to separate and can be recycled; a safe and low-toxicity solvent is used, and a solvent reflux dropwise adding process is adopted, so that the reversible reaction is continuously carried out towards the direction of synthesizing the menthyl benzoate, and the yield of the menthyl benzoate is higher; compared with the traditional synthetic method of menthyl benzoate, the method has the advantages that the sodium methoxide / magnesium oxide type solid base catalyst is a good catalyst for synthesizing menthyl benzoate, and the reaction is promoted by using one or a mixed solvent of dichloromethane, cyclohexane, n-heptane, cyclooctane and other solvents; the yield of the menthyl benzoate is higher, the experimental synthesis process is simple, and the application value is higher.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis, and specifically relates to a method for preparing D,L-menthyl benzoate. Background Art

[0002] Menthyl benzoate is a white transparent crystal with a light and refreshing mint flavor at room temperature. It is an important compound that can be used as a fixative in daily chemical industries such as daily chemical flavors. It can also be used as a solvent for oils, resins, etc. At the same time, menthyl benzoate is an important intermediate in the synthesis process of L-menthol and is a high-end fragrance with broad prospects.

[0003] Its classic synthesis method is to produce menthyl benzoate by esterification reaction of menthol and benzoic acid under the catalysis of strong acidic substances such as sulfuric acid or p-toluenesulfonic acid, or to synthesize it by transesterification reaction of benzoyl chloride and alcohol. Patent application number CN201210294449.9 discloses a synthesis method of menthyl benzoate, which uses p-toluenesulfonic acid to catalyze the reaction of menthol and benzoic acid to synthesize menthyl benzoate. After the reaction, water washing, alkali washing, drying and other processes are required, and a large amount of alkaline wastewater and waste solids are generated.

[0004] Patent application number CN201510809332.9 discloses a process for synthesizing L-menthol, which uses sodium methoxide and toluene to catalyze the synthesis of menthyl benzoate from menthol and methyl benzoate by a process of reaction and distillation. During the reaction, toluene is used to remove the generated methanol to promote the transesterification reaction. However, as the solvent evaporates, sodium methoxide tends to foam in the reactor, and the reaction will reach equilibrium earlier, resulting in unstable yield.

[0005] The existing technology uses strong acid substances as catalysts to catalyze the esterification of benzoic acid and menthol, which not only corrodes equipment but also seriously pollutes the environment. The technology using toluene as a solvent for reaction and distillation, as toluene evaporates, the ability to carry methanol becomes weaker, resulting in a low yield in the reversible transesterification reaction. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a method for preparing D,L-menthyl benzoate, which adopts sodium methoxide / magnesium oxide type solid base as a catalyst, a solvent as a reflux agent, and a menthol dripping process to catalyze methyl benzoate and DL-menthol for ester exchange reaction to synthesize menthyl benzoate. Under this process, menthol is continuously dripped into the reaction system, which can shift the reaction equilibrium to the right; and the solvent is continuously refluxed in the reactor to continuously bring out the generated methanol, thereby promoting the right shift of the reaction equilibrium and achieving a higher yield of the ester; 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 invention first provides a method for preparing D,L-menthyl benzoate, comprising the following steps: S1, methyl benzoate as a reaction substrate, first add sodium methoxide / magnesium oxide type solid base as a catalyst, then add half of the amount of solvent, menthol and the other half of the amount of solvent are mixed and added by titration, and the reaction is carried out by heating reflux. After the reaction is completed, the reaction system is naturally cooled to below 50°C; S2, filtering the cooled system to remove the catalyst, distilling the filtered solution under normal pressure, removing the solvent and methanol generated by the reaction at a high temperature of 75-170° C., and then distilling the obtained crude product of menthyl benzoate under reduced pressure to evaporate the unreacted excess methyl benzoate and trace menthol, and collecting the fraction at 130° C.-150° C. as the product menthyl benzoate; The preparation of the sodium methoxide / magnesium oxide type solid base as a catalyst comprises the following steps: S101, dissolving magnesium nitrate in deionized water completely, slowly adding ammonia water, stopping the addition when the pH value reaches 8, continuing to stir after the addition of ammonia water, filtering and washing the resulting precipitate until the pH reaches neutral, and filtering to separate the solid; S102, drying the solid washed in step S101, calcining to obtain magnesium oxide, taking a 20% methanol solution of sodium methoxide, and soaking the magnesium oxide for 24 hours; S103, drying the magnesium oxide soaked in step S102 under vacuum conditions, and finally calcining under inert gas protection to obtain a sodium methoxide / magnesium oxide type solid base catalyst.

[0008] Preferably, the mass ratio of methyl benzoate to menthol in step S1 is 1-3:1.

[0009] Preferably, the amount of the catalyst in step S1 is 1% to 30% of the mass of menthol, and the mass of the half amount of the solvent is 30-60% of the mass of menthol.

[0010] Preferably, the solvent in step S1 is selected from any one or more of dichloromethane, cyclohexane, n-heptane and cyclooctane.

[0011] Preferably, the heating reflux temperature in step S1 is 100° C.-180° C., and the heating reflux time is 2-10 h.

[0012] Preferably, in step S101, the solid-liquid ratio of magnesium nitrate to deionized water is 180 g:1 L, the concentration of the ammonia water is 25%, and the stirring time is 2 h.

[0013] Preferably, in step S102, the drying temperature is 120°C and the time is 12 hours; the calcination temperature is 500°C and the time is 4 hours.

[0014] Preferably, in the step S103, the drying temperature is 100°C and the time is 12 hours; the calcination temperature is 300°C and the time is 2 hours.

[0015] The mechanism of the catalytic reaction in this scheme is as follows: Sodium methoxide / magnesium oxide type solid base is used as a catalyst, magnesium oxide is used as a carrier, sodium methoxide is loaded on magnesium oxide, and calcination is performed to avoid sodium methoxide dissolving in the reaction liquid, so that solid-liquid separation and reuse are more convenient, and the defect of needing to neutralize sodium methoxide with acetic acid after each reaction is overcome, thereby reducing resource waste and alleviating environmental pollution.

[0016] The solvent is used as a reflux agent, and the menthol dripping process is adopted to catalyze the transesterification reaction of methyl benzoate and DL-menthol to synthesize menthyl benzoate. Under this process, menthol is continuously dripped into the reaction system, which can shift the reaction equilibrium to the right; and the solvent is continuously refluxed in the reactor, continuously taking out the generated methanol, promoting the right shift of the reaction equilibrium, 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.

[0017] Compared with the prior art, the present invention has the following beneficial effects: (1) Compared with the traditional synthesis method of menthyl benzoate catalyzed by toluenesulfonic acid, this scheme does not require water washing, alkali washing and other procedures, does not produce wastewater, has little environmental pollution, and does not corrode equipment. Compared with the synthesis method using sodium methoxide as a catalyst and toluene as a solvent, the use of solid base catalysts is easier to separate and reuse. The reflux of one or a mixed solvent such as cyclohexane, n-heptane, cyclooctane, etc. promotes the reaction and makes the yield of menthyl benzoate higher. The solvent is common and easy to obtain, easier to separate, safer, and more environmentally friendly. The experimental synthesis process is simple and has high application value.

[0018] (2) Using magnesium oxide as a carrier, sodium methoxide is loaded on magnesium oxide and calcined to prevent sodium methoxide from dissolving in the reaction solution, making solid-liquid separation and reuse more convenient. This overcomes the defect of needing to neutralize sodium methoxide with acetic acid after each reaction, thereby reducing resource waste and alleviating environmental pollution.

[0019] (3) This scheme adopts a mixed dropwise reflux process of one of the reaction substrates and a solvent, which can make the reversible ester exchange equilibrium reaction proceed continuously in the forward direction. The yield of menthyl benzoate is high, which can reach more than 99%. In addition, the preparation method is simple, the operation steps are few, the catalyst can be reused, and the production cost is low. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 It is the distribution chromatogram of the reaction products of Experimental Example 1; Figure 2 Schematic diagram of the experimental setup of Experimental Example 1. DETAILED DESCRIPTION

[0022] In order to make the technical problems, technical solutions and advantages to be solved by the present invention more clear, a detailed description will be given below with reference to the accompanying drawings and specific embodiments.

[0023] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Without departing from the spirit and substance of the present invention, modifications or substitutions made to the methods, steps or conditions of the present invention are within the scope of the present invention.

[0024] Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art; unless otherwise specified, the reagents used in the examples are commercially available.

[0025] Example 1 Preparation of sodium methoxide / magnesium oxide type solid base catalyst.

[0026] S1. Take 180 g of magnesium nitrate and dissolve it in 1000 mL of deionized water until it is completely dissolved. Slowly add 25% ammonia water and stop adding when the pH value reaches 8. Continue stirring for 2 hours after adding the ammonia water. Filter and wash the resulting precipitate until the pH reaches neutral, and filter and separate the solid. S2, drying the washed solid at 120°C for 12 hours, and finally calcining at 500°C for 4 hours to obtain magnesium oxide; S3. Take 100 g of 20% sodium methoxide methanol solution, soak the above magnesium oxide for 24 hours; dry at 100° C. for 12 hours under vacuum conditions, and finally calcine at 300° C. for 2 hours under inert gas protection to obtain a sodium methoxide / magnesium oxide type solid base catalyst.

[0027] Experimental Example 1 Synthesis of D,L-menthyl benzoate.

[0028] S1. In a 500 ml three-necked flask equipped with a stirring magnet, a thermometer, a constant pressure dropping funnel and a reflux condenser with a water separator, 40.8 g of methyl benzoate, 3.1 g of the sodium methoxide / magnesium oxide type solid base catalyst prepared in Example 1, and 15.6 g of a mixed solvent of cyclohexane and n-heptane (1:1) were added. A mixed solution of 31.2 g of menthol and 15.6 g of a mixed solvent of cyclohexane and n-heptane (1:1) was added to the constant pressure dropping funnel. The reflux temperature was controlled at 110°C. When the target temperature was reached, the mixed solution of menthol and the solvent was added dropwise and the timing was started. The reaction was continued for 10 hours. After the reaction was completed, the mixture was naturally cooled to 40°C. S2. The cooled solution was filtered through a sand core funnel to separate the solid catalyst to obtain a clear liquid, and the solution was distilled under normal pressure to evaporate the reflux agent and methanol at 100°C, and the remaining crude menthyl benzoate was subjected to vacuum distillation to evaporate the unreacted methyl benzoate and menthol, and the fraction at 130°C was collected as the product D,L-menthyl benzoate, with a yield of 99.05%.

[0029] The preparation mechanism is shown below:

[0030] Figure 1 This is a chromatogram of the distribution of reaction products, from left to right, methanol, methyl benzoate, menthol and menthyl benzoate. Taking menthol as the base unit, according to the area normalization method, menthol accounts for about 0.95% of the figure, and menthyl benzoate accounts for about 99.05%. The yield of menthyl benzoate is 99.05%.

[0031] Synthetic devices such as Figure 2 As shown, in Figure 2 A reaction substrate, a catalyst and a solvent are added to a reaction device, and after being heated to a certain temperature, the reactants react in an ester exchange reaction under the action of the catalyst, and the product methanol and the solvent are azeotropically produced together and enter the condenser above the water separator for condensation. The condensed liquid mixture is separated using the water separator, the solvent in the upper layer is refluxed into the round-bottom flask, and the methanol in the lower layer is continuously extracted.

[0032] Experimental Example 2 Synthesis of D,L-menthyl benzoate.

[0033] S1. Add 92g of methyl benzoate, 4.0g of sodium methoxide / magnesium oxide solid base, 40g of dichloromethane and cyclohexane mixed solvent (1:1) to 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. Add a mixture of 80g of menthol and 40g of cyclohexane and a mixture of dichloromethane and cyclohexane (1:1) to the constant pressure dropping funnel. Control the heating reflux temperature at 160°C. When the target temperature is reached, start dropping the mixture of menthol and solvent and start timing. React for 8h. After the reaction is completed, cool naturally to 40°C. S2. The cooled solution was filtered through a sand core funnel to separate the solid catalyst to obtain a clear liquid, and the solution was distilled under normal pressure to evaporate the reflux agent and methanol at 110°C, and the remaining crude menthyl benzoate was distilled under reduced pressure to evaporate the unreacted methyl benzoate and menthol, and the fraction at 150°C was collected as the product D,L-menthyl benzoate, with a yield of 98.8%.

[0034] Experimental Example 3 Synthesis of D,L-menthyl benzoate.

[0035] 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, add 78g of methyl benzoate, 1.6g of sodium methoxide / magnesium oxide solid base, and 40g of dichloromethane. Add a mixture of 80g of menthol and 40g of dichloromethane to the constant pressure dropping funnel. Control the heating reflux temperature at 120°C, start dripping the mixture of menthol and solvent at the target temperature, start timing, react for 6h, and cool naturally to 30°C after the reaction is completed; S2. The cooled solution was filtered through a sand core funnel to separate the solid catalyst to obtain a clear liquid, and the solution was distilled under normal pressure to evaporate the reflux agent and methanol at 90°C, and the remaining crude menthyl benzoate was distilled under reduced pressure to evaporate the unreacted methyl benzoate and menthol, and the fraction at 140°C was collected as the product, with a yield of 98.3%.

[0036] Experimental Example 4 Synthesis of D,L-menthyl benzoate.

[0037] 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, add 78g of methyl benzoate, 4.0g of sodium methoxide / magnesium oxide solid base, and 40g of cyclooctane. Add a mixture of 80g of menthol and 40g of cyclooctane to the constant pressure dropping funnel. Control the heating reflux temperature at 140°C, start dripping the mixture of menthol and solvent when the target temperature is reached, and start timing. React for 6h, and cool naturally to 40°C after the reaction is completed; S2. The cooled solution was filtered through a sand core funnel to separate the solid catalyst to obtain a clear liquid, and the solution was distilled under normal pressure to evaporate the reflux agent and methanol at 75°C, and the remaining crude menthyl benzoate was distilled under reduced pressure to evaporate the unreacted methyl benzoate and menthol, and the fraction at 140°C was collected as the product, with a yield of 97.6%.

[0038] Experimental Example 5 Synthesis of D,L-menthyl benzoate.

[0039] 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, add 82g of methyl benzoate, 3.13g of sodium methoxide / magnesium oxide solid base, and 31.5g of cyclohexane. Add a mixture of 63g of menthol and 31.5g of cyclohexane to the constant pressure dropping funnel. Control the heating reflux temperature at 150°C. When the target temperature is reached, start dripping the mixture of menthol and solvent and start timing. React for 2h. After the reaction is completed, cool naturally to 40°C. S2. Filter the cooled solution with a sand core 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 the unreacted methyl benzoate and menthol. Collect the fraction at 130°C as the product with a yield of 96.3%. Comparative Example 1 D,L-menthyl benzoate was prepared using sodium methoxide as a catalyst.

[0040] 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 30mL of toluene were added respectively. After stirring evenly at room temperature, the temperature of the reaction system was raised to 110℃, and the reaction was carried out while distilling. The first materials distilled out were methanol and toluene, respectively. Then, the vacuum distillation was changed to obtain excess methyl benzoate and unreacted D,L-menthol, respectively. Finally, the product D,L-menthol benzoate was obtained by vacuum distillation with a yield of only 75%.

[0041] It can be seen from this that the yield of sodium methoxide as a catalyst alone is much lower than the yield achieved by the product catalyzed by sodium methoxide / magnesium oxide type solid base catalyst. This is because the use of sodium methoxide alone and the process of distillation during reaction will cause the solvent toluene to evaporate. In the later stage, there is only a small amount of solvent in the reactor, which cannot smoothly carry out the methanol generated by the reaction, causing the reaction to reach equilibrium prematurely, thereby significantly reducing the yield.

[0042] Experimental Example 6 The recycling characteristics of sodium methoxide / magnesium oxide type solid base catalyst were investigated.

[0043] S1. The reaction materials in Example 1 were filtered and separated, and the separated sodium methoxide / magnesium oxide solid base catalyst was added to a three-necked flask again, and 40.8g of methyl benzoate, 15.6g of dichloromethane, and a mixture of 31.2g of DL-menthol and 15.6g of dichloromethane as a reflux agent were added. The heating reflux temperature was controlled at 110°C, and when the target temperature was reached, the mixture of menthol and solvent was added dropwise and the timing was started. The reaction was continued for 2h, and the reaction was cooled naturally to 40°C after the reaction was completed.

[0044] S2. The cooled solution was filtered through a sand core funnel to separate the solid catalyst to obtain a clear liquid, and the solution was distilled under normal pressure to evaporate the reflux agent and methanol at 100°C, and the remaining crude menthyl benzoate was distilled under reduced pressure to evaporate the unreacted methyl benzoate and menthol, and the fraction at 130°C was collected as the product D,L-menthyl benzoate, with a yield of 98.1%.

[0045] After the catalyst was recycled for 8 times, the yield of each cycle was shown in Table 1 below, and a relatively high yield could still be obtained. After the reaction was completed, the yield of D,L-menthyl benzoate was 95.3%.

[0046]

[0047] This indicates that the catalyst prepared by this scheme is cyclically stable and can still achieve a yield of 95.3% after 8 cycles, which is significantly better than the single sodium methoxide catalyst.

[0048] The above is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments. For those skilled in the art, improvements and changes obtained without departing from the technical concept of the present invention should also be regarded as the protection scope of the present invention.

Claims

1. A method for preparing D,L-menthyl benzoate, characterized in that: The following steps are involved: S1, methyl benzoate as a reaction substrate, first add sodium methoxide / magnesium oxide type solid base as a catalyst, then add half of the amount of solvent, menthol and the other half of the amount of solvent are mixed and added by titration, and the reaction is carried out by heating reflux. After the reaction is completed, the reaction system is naturally cooled to below 50°C; S2, filtering the cooled system to remove the catalyst, distilling the filtered solution under normal pressure, removing the solvent and methanol generated by the reaction at a high temperature of 75-170° C., and then distilling the obtained crude product of menthyl benzoate under reduced pressure to evaporate the unreacted excess methyl benzoate and trace menthol, and collecting the fraction at 130° C.-150° C. as the product menthyl benzoate; The preparation of the sodium methoxide / magnesium oxide type solid base as a catalyst comprises the following steps: S101, dissolving magnesium nitrate in deionized water completely, slowly adding ammonia water, stopping the addition when the pH value reaches 8, continuing to stir after the addition of ammonia water, filtering and washing the resulting precipitate until the pH reaches neutral, and filtering to separate the solid; S102, drying the solid washed in step S101, calcining to obtain magnesium oxide, taking a 20% methanol solution of sodium methoxide, and soaking the magnesium oxide for 24 hours; S103, drying the magnesium oxide soaked in step S102 under vacuum conditions, and finally calcining under inert gas protection to obtain a sodium methoxide / magnesium oxide type solid base catalyst.

2. The preparation method according to claim 1, characterized in that: 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% to 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 preparation method according to claim 1, characterized in that: In step S1, the solvent is selected from any one or more of dichloromethane, cyclohexane, n-heptane, and cyclooctane.

5. The preparation method according to claim 1, characterized in that: The heating reflux temperature in step S1 is 100° C.-180° C., and the heating reflux time is 2-10 h.

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

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

8. The preparation method according to claim 1, characterized in that: In the step 103, the drying temperature is 100° C. and the time is 12 h; the calcination temperature is 300° C. and the time is 2 h.

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