CN102701933A - Method for synthesizing curcumin through catalysis of alumina supported potassium fluoride solid base - Google Patents

Abstract

The invention provides a green synthetic method of curcumin, which comprises the steps as follows: alumina supported potassium fluoride solid base is taken as a catalyst, and boric anhydride is used for protecting active methylene groups of diacetone; diacetone and 4-hydroxyl-3-methoxy-benzaldehyde are dissolved in a polar aprotic solvent, and condensation reaction is performed; a hydrophobic organic solvent is added, the catalyst is filtered out and recovered for reutilization; dilute hydrochloric acid is added for hydrolysis; liquid separation and washing are carried out; the solvent is removed through rotary evaporation; and recrystallization and drying are carried out so as to obtain curcumin. The green synthetic method has the advantages as follows: the operation of the synthetic method is simple, the reaction yield coefficient is high, the product purity is high, and zero environmental contamination can be achieved; the catalyst is convenient to prepare, is economical to buy, achieves good stability, and can be reused through simple treatment or no treatment; the catalyst and products are easy to be separated, and the reaction condition is mild; and the green synthetic method is a green aseptic synthetic route, and achieves a favorable industrialized prospect.

Description

A kind of method adopting aluminum oxide supported potassium fluoride solid base to catalyze the method for synthesizing curcumin

technical field

The invention relates to a method for synthesizing curcumin, in particular to a green method for synthesizing curcumin from acetylacetone and 4-hydroxy-3-methoxybenzaldehyde by using aluminum oxide supported potassium fluoride as a catalyst.

Background technique

Curcumin is a natural pigment extracted from the ancient herbal medicine turmeric, and its content in turmeric is about 3% to 6%. Curcumin has been used in food coloring and traditional Chinese medicine. Because of its anti-inflammatory, anti-oxidant, antibacterial, anti-tumor, blood lipid-lowering, anti-aging and prolonging life and many other effects, it has become a research hotspot in the natural medicine industry in recent years. As an ideal yellow natural pigment, curcumin is non-toxic, strong in coloring power, good in dispersibility, light and heat resistant. Curcumin also has important applications in functional cosmetics. For example, Shiseido has found out the mechanism of facial wrinkles due to ultraviolet rays, and has successfully developed a drug "Yujin Jing" that successfully inhibits the formation of wrinkles with curcumin as the main component.

At present, almost all synthetic routes of curcumin are obtained through the condensation of acetylacetone and 4-hydroxy-3-methoxybenzaldehyde, wherein boric anhydride is used to protect the active methylene in acetylacetone. Its reaction equation is as follows:

According to the patent CN 101454267A, curcumin is obtained as follows: using high-grade, aprotic solvents, using aliphatic or araliphatic amines as catalysts, using azeotropes to remove the water produced by the reaction, making vanillin and acetylacetone condense, and then Do postprocessing. The yield of curcumin obtained by the method is good, and the price of the catalyst used in the reaction is relatively low. However, the catalyst is difficult to separate, cannot be recycled, causes waste of resources, and has certain harm to human beings, which aggravates environmental pollution.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies of the prior art and provide a green preparation method of curcumin under the catalysis of aluminum oxide supported potassium fluoride solid base.

To achieve the above object, the technical solution adopted in the present invention is:

1. Dissolve a certain amount of boric anhydride in solvent A, add acetylacetone to react, and use tributyl borate as a dehydrating agent. 0.5-1 mol% boric anhydride is used relative to acetylacetone, the reaction time is 10-40min, the reaction temperature is 45-75°C, solvent A is an aprotic polar solvent, including but not limited to DMF, DMAC, HMP, etc. .

2. Add 4-hydroxy-3-methoxybenzaldehyde and aluminum oxide supported potassium fluoride solid base catalyst to continue the reaction. After the reaction is finished, add solvent B, heat filter, and recycle the aluminum oxide-supported potassium fluoride solid base catalyst. The molar ratio of 4-hydroxy-3-methoxybenzaldehyde to acetylacetone is 1.8-1:1-4, the reaction time is 0.5-10 hours, and the reaction temperature is 70-130°C. Solvent B is a hydrophobic organic solvent, including but not limited to ethyl acetate, cyclohexane, 1,2-dichloroethane and the like. The catalyst used is aluminum oxide supported potassium fluoride solid base catalyst, and the catalyst consumption is 0.5～15wt.% of raw material 4-hydroxyl-3-methoxybenzaldehyde quality, and the mass fraction of loaded KF is 5% of the total amount of catalyst. ~40wt.%, the calcination temperature in the catalyst preparation process is 120-550°C. After the reaction is completed, the catalyst can be used directly after being filtered or washed with methanol, dried and reused.

3. Add excess 0.4mol/L dilute hydrochloric acid solution to the mixture to complete the reaction. The reaction time is 0.5-2 hours, and the reaction temperature is 40-65°C. The layers were allowed to stand, the aqueous layer was extracted with solvent B, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried.

Compared with the prior art, the positive effects of the present invention are: the synthesis method is simple to operate, the reaction yield is high, the product purity is good, no pollution to the environment, the catalyst is convenient to prepare, economical to purchase, good in stability, and can be easily processed or It can be reused without treatment, the catalyst and the product are easy to separate, and the post-treatment of the product is simple. It is a green and clean synthesis route with environmental protection functions. Therefore, the solid base prepared by supporting potassium fluoride on alumina is expected to become a new generation of environmentally friendly catalysts for the synthesis of curcumin.

Detailed ways

The present invention will be described in detail below through the examples, but it should not be considered as a limitation of the present invention.

Embodiment 1: in the 100ml there-necked flask that has stirrer, thermometer, reflux condenser, drying tube, add boric acid anhydride 5mmol, DMF 1ml, after dissolving, add in the acetylacetone of 5mmol. Raise the temperature to 65°C, add 10 mmol of tributyl borate, and stir for 10 min. Subsequently, 9 mmol of 4-hydroxy-3-methoxybenzaldehyde was added, stirred and dissolved, and the temperature was raised to 95° C., and reacted for 6 hours. Add 20ml of ethyl acetate, and after the temperature drops to 50°C, add 20ml of 0.4mol/L dilute hydrochloric acid solution to react for 1h. The layers were allowed to stand, the aqueous layer was extracted three times with ethyl acetate, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. The yield was 31.9%.

Example 2: Add 5 mmol of boric anhydride and 1 ml of DMF to a 100 ml three-neck flask equipped with a stirrer, a thermometer, a reflux condenser, and a drying tube. After dissolving, add 5 mmol of acetylacetone. Raise the temperature to 65°C, add 10 mmol of tributyl borate, and stir for 10 min. Subsequently, 9 mmol of 4-hydroxy-3-methoxybenzaldehyde was added, stirred and dissolved. Add 0.1 g of 15wt.% KF/Al ₂ O ₃ calcined at 450°C, heat to 90°C, and react for 4 hours. Add 20ml of ethyl acetate, filter while hot, and recycle the catalyst. Add 20ml of 0.4mol/L dilute hydrochloric acid solution to the reaction solution, and react at 50°C for 1h. The layers were allowed to stand, the aqueous layer was extracted three times with ethyl acetate, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. The yield was 62%.

Example 3: Add 5 mmol of boric anhydride and 1 ml of DMF to a 100 ml three-neck flask equipped with a stirrer, a thermometer, a reflux condenser, and a drying tube. After dissolving, add 5 mmol of acetylacetone. Raise the temperature to 65°C, add 10 mmol of tributyl borate, and stir for 10 min. Subsequently, 9 mmol of 4-hydroxy-3-methoxybenzaldehyde was added, stirred and dissolved. Add 0.1 g of 37wt.% KF/Al ₂ O ₃ calcined at 450°C, heat to 90°C, and react for 4 hours. Add 20ml of ethyl acetate, filter while hot, and recycle the catalyst. Add 20ml of 0.4mol/L dilute hydrochloric acid solution to the reaction solution, and react at 50°C for 1h. The layers were allowed to stand, the aqueous layer was extracted three times with ethyl acetate, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. The yield was 45%.

Example 4: Add 5 mmol of boric anhydride and 1 ml of DMF to a 100 ml three-neck flask equipped with a stirrer, a thermometer, a reflux condenser, and a drying tube. After dissolving, add 5 mmol of acetylacetone. Raise the temperature to 65°C, add 10 mmol of tributyl borate, and stir for 10 min. Subsequently, 9 mmol of 4-hydroxy-3-methoxybenzaldehyde was added, stirred and dissolved. Add 0.3 g of 15wt.% KF/Al ₂ O ₃ calcined at 450°C, heat to 90°C, and react for 4 hours. Add 20ml of ethyl acetate, filter while hot, and recycle the catalyst. Add 20ml of 0.4mol/L dilute hydrochloric acid solution to the reaction solution, and react at 50°C for 1h. The layers were allowed to stand, the aqueous layer was extracted three times with ethyl acetate, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. The yield was 57%.

Example 5: Add 5 mmol of boric anhydride and 1 ml of DMF to a 100 ml three-neck flask equipped with a stirrer, a thermometer, a reflux condenser, and a drying tube. After dissolving, add 5 mmol of acetylacetone. Raise the temperature to 65°C, add 10 mmol of tributyl borate, and stir for 10 min. Subsequently, 9 mmol of 4-hydroxy-3-methoxybenzaldehyde was added, stirred and dissolved. Add 0.3 g of 10% KF/Al ₂ O ₃ calcined at 250°C, heat to 90°C, and react for 4 hours. Add 20ml of ethyl acetate, filter while hot, and recycle the catalyst. Add 20ml of 0.4mol/L dilute hydrochloric acid solution to the reaction solution, and react at 50°C for 1h. The layers were allowed to stand, the aqueous layer was extracted three times with ethyl acetate, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. The yield was 63.2%.

The above descriptions are only preferred implementations of the present invention, and it should be pointed out that those skilled in the art will not depart from the concept of the present invention. Several improvements and modifications can also be made, and these improvements and modifications should also be considered within the protection scope of the present invention.

Claims (2)

1. a kind of method that adopts aluminum oxide to support potassium fluoride solid alkali catalysis to synthesize curcumin, is characterized in that: one, boric anhydride is dissolved in aprotic polar solvent, and this aprotic polar solvent includes but not limited to DMF , DMAC, HMP, then add acetylacetone to react, and use tributyl borate as a dehydrating agent; 2. Add 4-hydroxyl-3-methoxybenzaldehyde and aluminum oxide supported potassium fluoride solid base catalyst to continue the reaction. After the reaction is over, add a hydrophobic organic solvent, which includes but not limited to ethyl acetate, cyclohexane, 1,2-dichloroethane, and then hot filter, the aluminum oxide loaded potassium fluoride solid base catalyst Recycling; 3. Add excessive 0.4mol/L dilute hydrochloric acid solution to the filtrate to complete the reaction. The layers were allowed to stand, the aqueous layer was extracted three times with a hydrophobic organic solvent, the organic layers were combined, washed with water until neutral, the solvent was removed by rotary evaporation, recrystallized to obtain orange-yellow crystals, and dried. 2. a kind of method that adopts alumina-loaded potassium fluoride solid base catalysis to synthesize curcumin according to claim 1 is characterized in that the catalyzer that second step uses is alumina-loaded potassium fluoride solid base catalyst, and the catalyst consumption It is 0.5-15wt.% of the mass of the raw material 4-hydroxy-3-methoxybenzaldehyde, the mass fraction of the loading KF is 5-40wt.% of the total amount of the catalyst, and the calcination temperature in the catalyst preparation process is 120-550°C After the reaction is completed, the catalyst can be used directly after being filtered or washed with methanol, dried and reused.