KR20200001327A - Method for preparing curcumin hydrogenation products - Google Patents

Abstract

The present invention relates to a method for manufacturing curcumin hydride for antioxidant, antibacterial, and anti-inflammatory uses. According to the present invention, there is an effect of providing the method for manufacturing hydride by continuously conducting hydrogenation of curcumin with a high melting point and low solubility in a solvent under a solid catalyst.

Description

Method for preparing curcumin hydride {METHOD FOR PREPARING CURCUMIN HYDROGENATION PRODUCTS}

The present invention relates to a method for preparing curcumin hydride for antioxidant, antibacterial, and anti-inflammatory applications, and more particularly, a method for preparing hydride by continuously hydrogenating curcumin under a solid catalyst with high melting point and low solubility in a solvent. It is about.

Various health functional foods and health supplements have been proposed for disease-free longevity, and in particular, they are used for various purposes through the direct use of natural products or through extraction and conversion. Turmeric is used in various foods and natural medicines, especially in India. The effectiveness of turmeric is due to its potent antioxidant, anti-inflammatory and antibacterial activity. In addition, curcumin has optical properties, and because it absorbs ultraviolet rays, it is also used for sun protection purposes in India. Turmeric has an antioxidant effect on the whole body when ingested, and when applied to the skin, the same action occurs on the skin, thereby relieving and treating skin diseases such as atopic dermatitis, psoriasis and eczema. In India, creams formulated by grinding turmeric are sold for skin treatment. Curcumin content of 2-4% when turmeric is used, it does not show a great effect because the skin absorption is low, it is difficult to apply the skin due to the strong yellow color of curcumin. In the case of tetrahydrocurcumin can be obtained by adding hydrogen to the oxygen contained in the curcumin structure, 50% of curcumin absorbed by the human body when ingesting curcumin is converted to tetrahydrocurcumin has been reported to work. Prior arts related to the effects and preparation methods of such curcumin derivatives are disclosed in Korean Patent Laid-Open No. 2012-0040957.

Specifically, hydrogenation of curcumin has been reported in many literatures. For example, in the case of the synthesis of tetrahydrocurcumin through hydrogenation in a batch reactor, curcumin was dissolved in an organic solvent in a pressurized reactor and a catalyst was added and then pressurized with hydrogen. The reaction is performed by mixing in a state. However, such a batch reaction requires a time that is substantially independent of the reaction, such as input of raw materials, heating up to the reaction temperature, discharge of the reaction product, and there is a problem that the productivity of the reactor is lowered. In addition, in order to repeatedly use the catalyst, a separation process between the catalyst and the product is required, and there is a problem of premature deactivation of the catalyst due to a change in temperature or the like.

Therefore, there is a need to develop a method and a related device for continuously producing a high-efficiency curcumin hydride and a low solubility in a solvent.

An object of the present invention is to continuously prepare a hydride of the desired curcumin by performing a hydrogenation reaction in a continuous manner in the presence of a solid catalyst using a curcumin high melting point and low solubility in a solvent, which was difficult to efficiently continuously react conventionally A method and apparatus are provided.

While the present inventors have studied how to efficiently carry out the hydrogenation reaction of curcumin in a continuous manner, the hydrogen supply device used as the reaction gas is connected to the hydrogenation reactor and the raw material storage tank, and the curcumin raw material is hydrogenated under pressurization with hydrogen. The hydrogen gas supplied to the reactor and discharged was confirmed to be capable of carrying out a continuous reaction in a fixed bed reactor or the like according to a method of recycling, and thus, the present invention was completed.

According to one embodiment of the present invention, a method for continuously producing a hydride of curcumin by hydrogenating curcumin having a melting point of 180 ° C. or higher in a solvent in the presence of a solid catalyst, the hydrogen gas discharged from the reactor is introduced into the reactor The present invention provides a method for preparing curcumin hydride in which a hydrogenation reaction is performed in a state of compensating hydrogen adsorption efficiency of a solid catalyst in a reactor by circulating the curcumin as a raw material.

According to another embodiment of the present invention, in the apparatus for continuously producing a hydride of curcumin by hydrogenating curcumin having a melting point of 180 ℃ or more in a solvent in the presence of a solid catalyst, a hydrogenation reactor, a storage tank of curcumin raw material, and hydrogen It includes a supply device, it provides a device for producing a curcumin hydride which is connected to the hydrogen supply reactor and the storage tank of the curcumin raw material.

According to the present invention, the hydrogen supply device used for the reaction is connected to the hydrogenation reactor and the raw material storage tank, and the hydrogen gas is supplied to the hydrogenation reactor while the raw material is pressurized with hydrogen, and the discharged hydrogen gas is recycled in a fixed bed without a separate catalyst separation process. By optimizing the continuous reaction in the reactor, etc., it is possible to compensate for the disadvantages of the conventional batch reactor and to increase the energy efficiency and productivity.

1 is a view showing a hydrogenation apparatus of curcumin according to the present invention.
2 is a diagram showing the results of infrared spectroscopy analysis of tetrahydrocurcuminoids, which are curcumin hydrides synthesized according to an embodiment of the present invention.
3 is a graph showing the correlation between the reaction temperature, the reaction pressure and the conversion rate, which is an operating condition for synthesizing the tetrahydrocurcuminoid synthesized curcumin hydride according to an embodiment of the present invention.
4 is a graph showing a correlation between space velocity and conversion rate in the synthesis of tetrahydrocurcuminoid, a curcumin hydride synthesized according to an embodiment of the present invention.
FIG. 5 is a graph showing a correlation between a reaction pressure and a conversion rate at a constant reaction temperature, which is an operating condition for synthesizing tetrahydrocurcuminoid, which is a curcumin hydride synthesized according to an embodiment of the present invention.

Hereinafter, with reference to the accompanying drawings will be described in detail with respect to the continuous production method of the curcumin hydride of the present invention.

Curcumin of the present invention is an aromatic dicarboxylic acid having a melting point of 180 ° C. or higher, and such aromatic dicarboxylic acid has low solubility in water or various organic solvents.

The reaction targeted by the present invention is a hydrogenation reaction in the presence of a solid catalyst using the above raw material, specifically, a reaction in which curcumin is contacted with hydrogen gas in the presence of a solid catalyst to hydrogenate the unsaturated group contained in the backbone.

Examples of the hydride of curcumin obtained by these reactions (hereinafter referred to as reaction products) include hydrogenated unsaturated groups contained in the backbone, hexahydrocurcumin, tetrahydrocurcumin, or beta-diketone thereof.

For example, the hydride of curcumin can be represented by the following reaction scheme:

Since these compounds generally have a lower melting point than curcumin as a raw material, they can be taken out of the reactor in a molten state. For example, the melting point of curcumin is 180-185 ° C, while the melting point of hexahydrocurcumin is 80-82 ° C, and the melting point of tetrahydrocurcumin is 93-98 ° C.

The solvent used in the present invention is not particularly limited as long as it meets the purpose, but a solvent having high reactivity with curcumin as a raw material is not used. For example, ethanol or acetone is preferably used.

In the present invention, the hydrogenation reaction is continuously performed using a solid catalyst, and the type of solid catalyst to be used is not particularly limited as long as it is a solid catalyst suitable for hydrogenation of curcumin. For example, when tetrahydrocurcumin is produced by hydrogenating the side chain of curcumin, a catalyst in which metal such as palladium or ruthenium is supported on a carbon support having high hydrogen selectivity such as activated carbon can be used.

According to one embodiment of the present invention, a method for continuously producing a hydride of curcumin by hydrogenating curcumin having a melting point of 180 ° C. or higher in a solvent in the presence of a solid catalyst, the hydrogen gas discharged from the reactor is introduced into the reactor The present invention provides a method for preparing curcumin hydride in which a hydrogenation reaction is performed in a state of compensating hydrogen adsorption efficiency of a solid catalyst in a reactor by circulating the curcumin as a raw material.

1 shows a configuration of a manufacturing apparatus according to an embodiment of the present invention.

Referring to FIG. 1, the solvent in which curcumin is dissolved is supplied by the pressure difference between the hydrogenation reactor 11 and the storage tank 12 of curcumin raw material, and the residence time, which is the reaction time, is adjusted by adjusting the flow rate using a valve. . As the hydrogenation reactor 11, the solution is passed through a fixed packed column (for example, a cylinder type single column), and the solution is completed in the collection vessel 14. The tetrahydrocurcumin conversion solution stored in the collection container 14 is discharged from the bottom to separate the solvent and tetrahydrocurcumin to recover the tetrahydrocurcumin.

According to the present invention, since the storage tank 12 filled with the curcumin solution is pressurized with hydrogen, hydrogen may be dissolved in a solvent to improve reactivity.

As the catalyst charged in the hydrogenation reactor 11, various palladium precursors are taken and dissolved in various solvents to prepare a palladium precursor solution. The carbon selected as a support for the palladium catalyst having a very high selectivity for hydrogen uses activated carbon, graphene, carbon nanotubes, etc. in order to use a large specific surface area. The carbon carrier is preferably used after washing with nitric acid solution and washing it three more times with purified water and then drying. The support of the palladium can also obtain a high degree of dispersion by the excess solution impregnation method.

The washed and dried carbon carrier (eg activated carbon) is placed in a round flask, followed by the addition of a palladium precursor solution, followed by mixing and supporting using a rotary evaporator. After the purified water is evaporated and removed, the carbon body carrying the palladium precursor is dried in a drier. The dried carbon bodies are reduced by heating to 400-500 ° C. in a hydrogen atmosphere in an electric furnace to complete the carbon bodies loaded with palladium. In this case, the reduction temperature may be a temperature of a conventional reduction reaction.

The prepared Pd / C catalyst is charged to the tubular reactor 11 installed vertically. After charging, the reactor temperature is maintained at 100 to 500 ° C. to remove the adsorbed impurities to complete the catalyst filling of the reactor.

The storage tank 12 of the raw curcumin is charged by dissolving curcumin in ethanol or acetone at a concentration of 0.5 to 5.0 wt.%, Or 0.5 to 2.0 wt.%. Curcumin is insoluble and exhibits the highest solubility in alcohols in organic solvents. After filling the feed tank it is pressurized to 1.1-100 bar with hydrogen gas. At this time, since the pressurized pressure is proportional to the amount of hydrogen dissolved in alcohol, using a high pressure may improve the reaction rate. It is desirable to maintain a pressure above which the feed can be made by keeping it above the pressure in the catalyst packed column. The catalyst packed column is adjusted to a range of 1 to 10 bar using hydrogen gas, and the reaction rate decreases due to the adsorption of hydrogen at 1 bar or less, and the increase of the reaction rate is very insignificant above 10 bar. Therefore, the pressure is optimal 2 to 4 bar. In addition, the temperature is performed in the range of room temperature to 60 ℃. Below room temperature, the reaction rate is slow, and above 60 ° C, the catalytic surface adsorption of hydrogen is reduced, thereby reducing the reactivity. Optimum conditions are 50-60 degreeC is the best (refer FIG. 3). Since the hydrogen selectivity of the carbon carrier and palladium is very high, the effect of the above pressure on the reactivity improvement is insignificant. After the catalyst packed column 11 is pressurized with hydrogen, an ethanol solution in which curcumin is dissolved is supplied to the top of the column 11 using the liquid mass feeder 21. The supplied curcumin solution flows to the lower part of the column 11 by gravity, and comes into contact with the catalyst to undergo a hydrogenation reaction.

 That is, according to another embodiment of the present invention, in the apparatus for continuously producing a hydride of curcumin by hydrogenating curcumin having a melting point of 180 ℃ or more in a solvent in the presence of a solid catalyst, the hydrogenation reactor (11), storage of curcumin raw material A tank 12 and a hydrogen supply device 13, wherein the hydrogen supply device 13 is connected to the hydrogenation reactor 11 and the storage tank 12 of curcumin raw material. It provides a manufacturing apparatus.

Referring again to FIG. 1, curcumin, which is a raw material mixed with a solvent, is pressurized with hydrogen gas discharged from the supply tank 13 of hydrogen in the supply tank 12 or from the reactor in the reactor 13, and the pressure conditions in the reactor In this case, the entire amount of the raw material is adjusted to a concentration that can be dissolved in the solvent containing the reaction product.

When pressurized by the hydrogen gas discharged from the reactor in the reactor 13 and when pressurized by the hydrogen gas discharged from the hydrogen supply tank 13, respectively, the flow rate using the control valve 23 or the like as shown in FIG. Etc. can be adjusted. The hydrogen supply position may be other than the reactor 13, the raw material supply tank 12 for pressurizing the curcumin solution as the raw material with hydrogen, or the raw material supply line for supplying the raw material solution to the reactor 13.

The supply position of curcumin, which is a raw material, is preferably at the upper end of the reactor 13 because it can maximize the reaction rate.

In the reactor 13, the curcumin solution, which is a raw material, is brought into contact with the fixed-phase catalyst and hydrogen to generate a hydrogenation reaction. At this time, the reactor 13 is provided through the liquid mass feeder 21 and the control valve 22 provided at the upper end of the reactor 13. It is possible to control the amount of raw curcumin solution to be automatically and semi-automatically added into the solution, and the amount and speed of hydrogen.

Usually, the hydrogenation reaction rate of curcumin is influenced by the amount of hydrogen gas dissolved in the reaction liquid. In the method of the present invention, the hydrogen adsorption amount of the catalyst can be increased by automatically or semi-automatically introducing the raw material of curcumin pressurized with hydrogen. It is therefore possible to proceed the reaction advantageously.

According to the method of the present invention, the hydrogen gas continuously discharged from the reactor is circulated, and the raw material of curcumin is recycled to the reactor under pressure.

In particular, since the general hydrogenation reaction is exothermic, it may be necessary to cool the reaction liquid by flowing it to a heat exchanger for heat control in order to control the heat, but in the present invention, the hydrogen gas continuously circulated from the reactor is circulated. It has advantages that are not related to processing.

In addition, the reaction product generated in the reactor is discharged to a separate collection container 14, it can be separated from the solvent to obtain a high purity product. Separation of the reaction product and the solvent may use a method used in a conventional chemical product manufacturing process. For example, the reaction product may be heated or cooled and then the solvent may be distilled off or the reaction product crystals may be produced and then the product may be recovered or the product crystals recovered.

According to the method of the present invention, since the raw material is completely dissolved in the reactor to perform the hydrogenation reaction in the reactor, it provides the advantage that there is no need to separate the catalyst separately. That is, according to the method of the present invention, it is possible to perform the reaction of the high melting point and poorly soluble curcumin in a continuous reaction under appropriate reaction conditions without using a large amount of solvent, so that the desired reaction product can be produced very efficiently. .

Hereinafter, the present invention will be described with reference to specific embodiments, but the technical spirit of the present invention is not limited by the following embodiments.

<Example>

Preparation Example 1 Tetrahydrocurcumin Synthesis Using 1 wt.% Pd / C Catalyst

Palladium nitrate [Pd (NO ₃ ) ₂ ] [Aldrich Chemical, USA] Take 1.912 g and dissolve in 130 g of purified water to prepare a palladium precursor solution. Activated carbon [Aldrich Chem, USA] was used to use carbon having a large specific surface area. Activated carbon was separated into 0.359 mm or less and washed with 0.5 mol of nitric acid, which was washed with purified water three more times and then dried. The supporting of palladium was used as an excess solution impregnation method, and the washed and dried activated carbon was put into a 1000 ml round flask, and then the palladium precursor solution was added, followed by mixing and supporting using a rotary evaporator. After the purified water was evaporated and removed, the carbon body carrying the palladium precursor was dried in a drier. The dried carbon body was reduced by heating to 400 ° C. in a hydrogen atmosphere in an electric furnace to complete a carbon body loaded with 1 wt.% Palladium.

Preparation Example 2 Tetrahydrocurcumin Synthesis Using 2 wt.% Pd / C Catalyst

The same procedure as in Preparation Example 1 was performed, except that 2 wt.% Pd / C was used instead of 1 wt.% Pd / C.

Preparation Example 3 Tetrahydrocurcumin Synthesis Using 5 wt.% Pd / C Catalyst

The same procedure as in Preparation Example 1 was carried out, except that 5 wt.% Pd / C was used instead of 1 wt.% Pd / C.

<Example 1>

The hydrogenation reactor 11 includes a reaction part and is made of stainless steel (SUS) having a diameter of 10 cm and a height of 80 cm, and the reaction part is filled with 1.5 kg of Pd / C, which is a heterogeneous catalyst.

Here, the Pd / C was charged using the one prepared in Preparation Example 1, and after the filling, the reactor temperature was maintained at 150 ° C. to remove adsorbed impurities, thereby completing the configuration of the reactor.

The raw material curcumin storage tank 12 was filled with 5 liters of curcumin dissolved in ethanol at a concentration of 1 wt.%. After filling, pressurized to 15 bar with hydrogen gas. At this time, since the pressurized pressure is proportional to the amount of hydrogen dissolved in alcohol, using a high pressure may improve the reaction rate.

The catalyst packed column 11 was adjusted to a range of 1 to 5 bar using hydrogen gas. Since the hydrogen selectivity of the carbon carrier and palladium is very high, the effect of the above pressure on the reactivity improvement is insignificant. The catalyst packed column 11 was pressurized with hydrogen, and then an ethanol solution in which curcumin was dissolved was supplied to the top of the column 11 using the liquid mass feeder 21. The supplied curcumin solution flowed to the lower part of the column 11 by gravity, and contacted with a catalyst to carry out a hydrogenation reaction.

<Example 2>

The same method as Example 1 was repeated except that 2 wt.% Pd / C of Preparation Example 2 was used instead of 1 wt.% Pd / C of Preparation Example 1, and the same method as Example 1 was repeated. .

<Example 3>

The same method as Example 1 was repeated except that 5 wt.% Pd / C of Preparation Example 3 was used instead of 1 wt.% Pd / C of Preparation Example 1, and the same method as Example 1 was repeated. .

<Example 4>

The same method as in Example 1 was repeated except that 2 wt.% Curcumin solution was used instead of 1 wt.% Curcumin solution.

Example 5

The same method as in Example 1 was repeated except that acetone solvent was used in 1 wt.% Curcumin solution instead of 1 wt.% Curcumin ethanol solution.

<Evaluation>

<Purity Assessment>

The purity of the tetrahydrocurcumin sample synthesized by the method shown in Example 1 and Aldrich, Inc., a standard used in the art, is shown in Table 1 below. Infrared spectroscopic analysis of the results are shown in FIG.

Tetrahydrocurcumin Purity Example 1 Comparative example 97.0 95.5

As shown in Table 1, it was confirmed that the tetrahydrocurcumin synthesized by the method provided by the present invention shows a high purity, infrared spectroscopy also confirmed the high purity.

<Conversion Rate Assessment>

Conversion rate according to temperature and reaction pressure during the reaction was measured and shown in FIG. 3. 3 is a graph comparing the results of using the apparatus of FIG. 1, using ethanol as a solvent, and supplying curcuminoids at a concentration of 1 mg / cc. The conversion rate of tetrahydrocurcumin according to temperature and pressure, respectively, was found to show excellent conversion at 30 to 60 psi in the range of 50 to 60 ° C.

In addition, Figure 4 shows the conversion rate for the flow rate at 60 ℃, 60 psi was confirmed that the conversion rate similar to the general batch reaction in the range of 75 minutes to 30 minutes in space time.

5 also shows the effect of pressure at the same temperature. The pressure affects the adsorption rate of hydrogen to carbon and palladium, and it was confirmed that it showed excellent conversion at about 4 atm.

11: hydrogenation reactor
12: storage tank of curcumin raw material
13: supply of hydrogen
14: collection container
21: liquid mass feeder
22: control valve

Claims (10)

A method for continuously producing curcumin hydride by hydrogenating curcumin having a melting point of 180 ° C. or higher in a solvent in the presence of a solid catalyst. A method for preparing curcumin hydride in which a hydrogenation reaction is performed in a state in which hydrogen adsorption efficiency of a solid catalyst is compensated for. The method of claim 1,
The hydrogenation reactor pressure is adjusted to within the range 1 ~ 10bar. The method of claim 1,
The curcumin raw material is prepared by dissolving curcumin in ethanol or acetone at a concentration of 0.5 to 5.0% by weight and then pressurizing the hydrogen to 1.1 to 100 bar with hydrogen gas. The method of claim 1,
The hydrogenation reactor temperature is controlled to be controlled at room temperature to 60 ℃ range. The method of claim 1,
Wherein said liquid tetrahydrocurcuminoid component is separated out of said reactor and said gaseous component is recycled to said gas storage device. The method of claim 1,
The hydrogenation reactor is a method in which the high activity catalyst is filled inside the carbon-supported state. An apparatus for continuously producing a hydride of curcumin by hydrogenating curcumin having a melting point of 180 ° C. or higher in a solvent in the presence of a solid catalyst, the apparatus comprising a hydrogenation reactor, a storage tank of curcumin raw material, and a hydrogen supply device. And a supply device connected to the hydrogenation reactor and the storage tank of curcumin raw material. The method of claim 7, wherein
An apparatus for producing a liquid tetrahydrocurcumin collection unit at the bottom of the hydrogenation reactor. The method of claim 7, wherein
The hydrogenation reactor is a cylinder type single column reactor. The method of claim 7, wherein
Wherein said cylinder type single column is internally charged with at least one high activity catalyst selected from the group consisting of palladium, nickel, platinum, ruthenium and rhodium.

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