A method for preparing vitamin c ethyl ether

Abstract

The application discloses a preparation method of vitamin C ethyl ether. The preparation method of vitamin C ethyl ether comprises the following steps: S11, reacting vitamin C and cyclopentanone to obtain 5,6-O-cyclopentyl-ascorbic acid; S12, adding chlorosulfoxide dropwise into ethanol to react, then adding 5,6-O-cyclopentyl-ascorbic acid and triethylamine to perform refluxing reaction to obtain 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether; S13, reacting 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether with dilute hydrochloric acid to obtain vitamin C ethyl ether; in addition, a solid catalyst is added in step S12. The solid catalyst prepared by a novel method is added in step S12 of the preparation method of vitamin C ethyl ether; the reaction time of step S12 can be shortened to 3-5 hours, and meanwhile, the yield of step S12 can be ensured to reach more than 80%. Compared with the prior art, the method disclosed by the application greatly shortens the reaction time of the core step, which is helpful to improve the production efficiency and further reduce the production cost.

Description

Technical Field

[0001] This invention relates to the field of compound preparation technology, and specifically to a method for preparing vitamin C ethyl ether. Background Technology

[0002] Vitamin C ethyl ether is a vitamin C derivative that can improve skin elasticity, inhibit tyrosinase activity, and inhibit melanin formation; therefore, it is a commonly used ingredient in cosmetics.

[0003] Chinese invention patent CN 113214197A discloses a method for preparing vitamin C ethyl ether; the specific method includes the following steps: Step 1: Using vitamin C as the starting material and cyclopentanone as the reactant and solvent, the mixture is reacted at 20-30℃ for 4 hours under the catalysis of acetyl chloride, filtered, and 5,6-O-cyclopentyl-ascorbic acid is obtained; Step 2: Thionyl chloride is added dropwise to ethanol, reacted at 0-5℃ for 1 hour, 5,6-O-cyclopentyl-ascorbic acid and triethylamine are added, the mixture is refluxed for 12 hours, evaporated under reduced pressure, ethyl acetate and water are added, and after separation, about 1 / 4 of the ethyl acetate is evaporated, crystallized at 0-5℃ for 2 hours, and filtered to obtain 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether; Step 3: 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether is reacted with dilute hydrochloric acid at 50℃ for 2 hours, evaporated under reduced pressure, and the obtained product is recrystallized with ethanol to obtain vitamin C ethyl ether. Although the raw materials are readily available and the operation is simple, the core reaction step 2 requires a reaction time of 12 hours under reflux, which is relatively long and needs further improvement. Summary of the Invention

[0004] In order to overcome at least one of the technical problems existing in the prior art, the present invention provides a method for preparing vitamin C ethyl ether.

[0005] The technical solution of the present invention is as follows:

[0006] A method for preparing vitamin C ethyl ether includes the following steps:

[0007] S11. Reaction of vitamin C with cyclopentanone yields 5,6-O-cyclopentyl-ascorbic acid;

[0008] S12. Thionyl chloride was added dropwise to ethanol and reacted, followed by the addition of 5,6-O-cyclopentyl-ascorbic acid and triethylamine and refluxed to give 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether.

[0009] S13. Reaction of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether with dilute hydrochloric acid yields vitamin C ethyl ether;

[0010] Further, the solid catalyst is added in step S12.

[0011] Preferably, the solid catalyst is prepared by a method comprising the following steps:

[0012] S21. Take silica and add water, stir for 1-2 hours under ultrasonic condition to obtain a silica dispersion;

[0013] S22. Add zinc chloride and rare earth chloride into the silica dispersion, stir for 20-30 minutes, then add sodium bicarbonate, continue to stir for 3-5 hours, and then extract the solid by filtration;

[0014] S23. Calcine the solid at 1000-1200℃ for 2-4 hours to obtain a calcined solid;

[0015] S24. Soak the calcined solid in an aqueous phosphoric acid solution for 5-10 hours, take out, and then dry to obtain the solid catalyst.

[0016] The present application adds a solid catalyst prepared by a novel method in step S12 of preparing vitamin C ethyl ether; the reaction time of step S12 can be shortened to 3-5 hours, and the yield of step S12 can be ensured to be above 80%.

[0017] Preferably, the use amount ratio of silica to water in step S21 is 1kg:6-10L.

[0018] Preferably, the use amount ratio of silica to water in step S21 is 1kg:8L.

[0019] Preferably, the use amount ratio of silica dispersion to zinc chloride, rare earth chloride and sodium bicarbonate in step S22 is 10L:60-80g:130-150g:300-400g.

[0020] Preferably, the use amount ratio of silica dispersion to zinc chloride, rare earth chloride and sodium bicarbonate in step S22 is 10L:70g:140g:350g.

[0021] Preferably, the rare earth chloride in step S22 is selected from gadolinium chloride, thulium chloride or lutetium chloride.

[0022] Preferably, the rare earth chloride is composed of thulium chloride and lutetium chloride.

[0023] Preferably, the weight ratio of thulium chloride to lutetium chloride is 1-3:2-4.

[0024] Most preferably, the weight ratio of thulium chloride to lutetium chloride is 2:3.

[0025] The inventors surprisingly found in the research that, compared with adding single rare earth chloride gadolinium chloride, thulium chloride or lutetium chloride, adding rare earth chlorides composed of thulium chloride and lutetium chloride during preparation of the solid catalyst can greatly improve the yield of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether in the preparation step S12 of vitamin C ethyl ether. The solid catalyst prepared by adding rare earth chlorides composed of thulium chloride and lutetium chloride during preparation of the solid catalyst can synergistically improve the yield of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether in the preparation step S12 of vitamin C ethyl ether.

[0026] Preferably, the solid is calcined at 1100°C for 3h to obtain the calcined solid.

[0027] Preferably, the calcined solid is soaked in the aqueous phosphoric acid solution for 8h, then taken out and dried to obtain the solid catalyst.

[0028] Preferably, the aqueous phosphoric acid solution refers to an aqueous phosphoric acid solution with a mass fraction of 60%.

[0029] Preferably, the weight ratio of the solid catalyst to ethanol in step S12 is 1-3:100.

[0030] Beneficial effects: The present application provides a new preparation method of vitamin C ethyl ether. The present application adds a solid catalyst prepared by a new method in the preparation step S12 of vitamin C ethyl ether. The reaction time of step S12 can be shortened to 3-5h, and the yield of step S12 can be ensured to be more than 80%. Compared with the prior art, the method of the present application greatly shortens the reaction time of the core step, which helps to improve the production efficiency and further reduce the production cost. DETAILED DESCRIPTION

[0031] The present application will be further explained in combination with specific embodiments, but the embodiments do not limit the present application in any form.

[0032] Example 1: Preparation method of vitamin C ethyl ether

[0033] S11. 25kg of vitamin C, 175kg of cyclopentanone were added to a 500L reaction kettle, stirred uniformly, then 11.1kg of acetyl chloride was added, reacted at 25°C for 4h, then filtered, washed with cyclopentanone to obtain 5,6-O-cyclopentyl-ascorbic acid;

[0034] S12. Take 150 kg of ethanol into a 500 L reaction kettle, cool to 0°C, add 22.1 kg of thionyl chloride dropwise, stir at 0°C for 1 h, then add 30 kg of 5,6-O-cyclopentyl-ascorbic acid, and add 18.8 kg of triethylamine dropwise at 0°C, after the addition is completed, add 1.5 kg of solid catalyst, heat and stir to reflux, and reflux for 4 h, dry after concentration under reduced pressure to obtain a white solid; add 300 kg of ethyl acetate and 200 kg of water to the white solid, stir for 1 h, then separate the layers, remove 220 kg of ethyl acetate from the ethyl acetate layer under reduced pressure, cool to 0°C, and stir for 3 h, then filter and wash with cold ethyl acetate to obtain 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether;

[0035] S13. Take 27 kg of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether into a 500 L reaction kettle, then add 216 kg of hydrochloric acid, stir at 60°C for 2 h, then remove the solvent under reduced pressure to obtain a yellow oil; add 135 kg of ethanol to the yellow oil, heat to dissolve, then add 1.5 kg of activated carbon, heat to reflux for 0.5 h; after the reflux is completed, filter, cool the filtrate to -5°C, stir for 2 h, then filter again, and wash with cold ethanol to obtain vitamin C ethyl ether;

[0036] The solid catalyst in step S12 is prepared by the following method:

[0037] S21. Take silica and add water, stir for 1.5 h under ultrasonic conditions to obtain a silica dispersion; wherein the ratio of the amount of silica to water is 1 kg:8 L;

[0038] S22. Add zinc chloride and rare earth chloride to the silica dispersion, stir for 25 min, then add sodium bicarbonate, continue to stir for 4 h, then filter to obtain a solid; wherein the ratio of the amount of silica dispersion to zinc chloride, rare earth chloride, and sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is gadolinium chloride;

[0039] S23. Calcine the solid at 1100°C for 3 h to obtain a calcined solid;

[0040] S24. Soak the calcined solid in a 60% by mass phosphoric acid aqueous solution for 8 h, then take it out and dry to obtain the solid catalyst.

[0041] Preparation method of vitamin C ethyl ether according to Example 2

[0042] The preparation method of vitamin C ethyl ether according to Example 2 is different from Example 1 in that the preparation method of the solid catalyst in step S12 is different, and the rest is the same as Example 1.

[0043] The solid catalyst in step S12 is prepared by the following method:

[0044] S21. Take silica and add it to water, stir for 1.5 h under ultrasonic conditions to obtain a silica dispersion; wherein the use amount ratio of silica to water is 1 kg:8 L;

[0045] S22. Add zinc chloride and rare earth chloride to the silica dispersion, stir for 25 min, then add sodium bicarbonate, continue to stir for 4 h, and then suction filter to obtain a solid; wherein the use amount ratio of silica dispersion to zinc chloride, rare earth chloride and sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is thulium chloride;

[0046] S23. Calcine the solid at 1100℃ for 3 h to obtain a calcined solid;

[0047] S24. Soak the calcined solid in a 60% by mass phosphoric acid aqueous solution for 8 h, then take it out, and then dry to obtain the solid catalyst.

[0048] Preparation method of vitamin C ethyl ether

[0049] The preparation method of vitamin C ethyl ether in Example 3 is different from that in Example 1 in that the preparation method of the solid catalyst in step S12 is different, and the rest is the same as that in Example 1.

[0050] The solid catalyst in step S12 is prepared by the following method:

[0051] S21. Take silica and add it to water, stir for 1.5 h under ultrasonic conditions to obtain a silica dispersion; wherein the use amount ratio of silica to water is 1 kg:8 L;

[0052] S22. Add zinc chloride and rare earth chloride to the silica dispersion, stir for 25 min, then add sodium bicarbonate, continue to stir for 4 h, and then suction filter to obtain a solid; wherein the use amount ratio of silica dispersion to zinc chloride, rare earth chloride and sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is thulium chloride;

[0053] S23. Calcine the solid at 1100℃ for 3 h to obtain a calcined solid;

[0054] S24. Soak the calcined solid in a 60% by mass phosphoric acid aqueous solution for 8 h, then take it out, and then dry to obtain the solid catalyst.

[0055] Preparation method of vitamin C ethyl ether

[0056] The preparation method of the vitamin C ethyl ether in the embodiment 4 is different from the embodiment 1 in that the preparation method of the solid catalyst in the step S12 is different, and the rest is the same as the embodiment 1.

[0057] The solid catalyst in the step S12 is prepared by the following method:

[0058] S21. The silica is taken into water, and stirred under the ultrasonic condition for 1.5 h to obtain a silica dispersion liquid; wherein the use amount ratio of the silica to water is 1 kg:8 L;

[0059] S22. The zinc chloride and the rare earth chloride are added into the silica dispersion liquid, the sodium bicarbonate is added after stirring for 25 min, and the stirring is continued for 4 h, and then the solid is obtained by suction filtration; wherein the use amount ratio of the silica dispersion liquid to the zinc chloride, the rare earth chloride and the sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is composed of thulium chloride and lutetium chloride with a mass ratio of 2:3;

[0060] S23. The solid is calcined at 1100℃ for 3 h to obtain a calcined solid;

[0061] S24. The calcined solid is soaked in a phosphoric acid aqueous solution with a mass fraction of 60% for 8 h, taken out, and then dried to obtain the solid catalyst.

[0062] The preparation method of the vitamin C ethyl ether in the embodiment 5

[0063] The preparation method of the vitamin C ethyl ether in the embodiment 5 is different from the embodiment 1 in that the preparation method of the solid catalyst in the step S12 is different, and the rest is the same as the embodiment 1.

[0064] The solid catalyst in the step S12 is prepared by the following method:

[0065] S21. The silica is taken into water, and stirred under the ultrasonic condition for 1.5 h to obtain a silica dispersion liquid; wherein the use amount ratio of the silica to water is 1 kg:8 L;

[0066] S22. The zinc chloride and the rare earth chloride are added into the silica dispersion liquid, the sodium bicarbonate is added after stirring for 25 min, and the stirring is continued for 4 h, and then the solid is obtained by suction filtration; wherein the use amount ratio of the silica dispersion liquid to the zinc chloride, the rare earth chloride and the sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is composed of thulium chloride and lutetium chloride with a mass ratio of 2:3;

[0067] S23. The solid is calcined at 1100℃ for 3 h to obtain a calcined solid;

[0068] S24. The calcined solid is soaked in a 60% by mass aqueous phosphoric acid solution for 8 hours, taken out, and dried to obtain the solid catalyst.

[0069] The preparation method of the vitamin C ethyl ether in Example 6 is different from that in Example 1 in that the preparation method of the solid catalyst in step S12 is different, and the rest is the same as in Example 1.

[0070] The preparation method of the vitamin C ethyl ether in Example 6 is different from that in Example 1 in that the preparation method of the solid catalyst in step S12 is different, and the rest is the same as in Example 1.

[0071] The solid catalyst in step S12 is prepared by the following method:

[0072] S21. Silica is taken and added to water, and stirred under ultrasonic conditions for 1.5 hours to obtain a silica dispersion; wherein the ratio of the amount of silica to water is 1 kg:8 L;

[0073] S22. Zinc chloride and rare earth chloride are added to the silica dispersion, stirred for 25 minutes, then sodium bicarbonate is added, and stirring is continued for 4 hours, and then the solid is filtered out; wherein the ratio of the amount of the silica dispersion to zinc chloride, rare earth chloride and sodium bicarbonate is 10 L:70 g:140 g:350 g; the rare earth chloride is composed of gadolinium chloride and lutetium chloride in a mass ratio of 2:3;

[0074] S23. The solid is calcined at 1100°C for 3 hours to obtain a calcined solid;

[0075] S24. The calcined solid is soaked in a 60% by mass aqueous phosphoric acid solution for 8 hours, taken out, and dried to obtain the solid catalyst.

[0076] The yield results of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether in step S12 in the preparation of the vitamin C ethyl ether in Examples 1-6 are shown in Table 1.

[0077] Table 1. Yield of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether in step S12

[0078]

[0079]

[0080] As can be seen from the experimental data in Table 1, the yield of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether in step S12 in Examples 1-3 is all higher than 80%; this shows that in the preparation step S12 of the vitamin C ethyl ether, the solid catalyst prepared by the brand-new method described in the application is added; it can shorten the reaction time of step S12 to 3-5 hours, and at the same time can also ensure that the yield of step S12 reaches more than 80%.

[0081] As can be seen from the experimental data in Table 1, the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Example 4 reached 96.4%, which was much higher than the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Examples 2 and 3, and also much higher than the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Example 1. This indicates that the solid catalyst prepared by adding the rare earth chlorides composed of thulium chloride and lutetium chloride in the preparation process of the solid catalyst can synergistically improve the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of the preparation of vitamin C ethyl ether, and compared with adding a single rare earth chloride gadolinium chloride, thulium chloride or lutetium chloride, can greatly improve the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of the preparation of vitamin C ethyl ether.

[0082] As can be seen from the experimental data in Table 1, the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Example 4 reached 96.4%, which was much higher than the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Examples 2 and 3, and also much higher than the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of Example 1. This indicates that the solid catalyst prepared by adding the rare earth chlorides composed of thulium chloride and lutetium chloride in the preparation process of the solid catalyst can synergistically improve the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of the preparation of vitamin C ethyl ether, and compared with adding a single rare earth chloride gadolinium chloride, thulium chloride or lutetium chloride, can greatly improve the yield of 3-O-ethyl-5,6-O-cyclopentyl- ascorbic acid ether in step S12 of the preparation of vitamin C ethyl ether.

Claims

1. A method for preparing vitamin C ethyl ether, comprising the following steps: S11. Reaction of vitamin C with cyclopentanone yields 5,6-O-cyclopentyl-ascorbic acid; S12. Thionyl chloride was added dropwise to ethanol and reacted, followed by the addition of 5,6-O-cyclopentyl-ascorbic acid and triethylamine and refluxed to give 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether; S13. Reaction of 3-O-ethyl-5,6-O-cyclopentyl-ascorbic acid ether with dilute hydrochloric acid yields vitamin C ethyl ether; Its features are, A solid catalyst is also added in step S12; The solid catalyst is prepared by a method comprising the following steps: S21. Add silica to water and stir under ultrasonic conditions for 1-2 hours to obtain a silica dispersion; S22. Add zinc chloride and rare earth chloride to the silica dispersion, stir for 20-30 min, add sodium bicarbonate, continue stirring for 3-5 h, and then filter to obtain the solid. S23. The solid is calcined at 1000~1200℃ for 2~4 hours to obtain the calcined solid; S24. The calcined solid is soaked in a phosphoric acid aqueous solution for 5-10 hours, then removed and dried to obtain the solid catalyst described above; The rare earth chlorides mentioned in step S22 are selected from gadolinium chloride, thulium chloride, or lutetium chloride.

2. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, In step S21, the ratio of silicon dioxide to water is 1 kg: 6~10 L.

3. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, In step S22, the ratio of silica dispersion to zinc chloride, rare earth chloride, and sodium bicarbonate is 10L:60~80g:130~150g:300~400g.

4. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, In step S22, the ratio of silica dispersion to zinc chloride, rare earth chloride, and sodium bicarbonate is 10L:70g:140g:350g.

5. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, The solid was calcined at 1100℃ for 3 hours to obtain the calcined solid.

6. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, The calcined solid was soaked in a phosphoric acid aqueous solution for 8 hours, then removed and dried to obtain the solid catalyst.

7. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, In step S12, the weight ratio of the solid catalyst to ethanol is 1~3:

100.

8. The method for preparing vitamin C ethyl ether according to claim 1, characterized in that, The reflux reaction time in step S12 is 3-5 hours.

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