Method for preparing 4'-hydroxy-2,4,6-trimethoxy dihydrocharcone
Technical Field This invention involves a kind of lourerin B that is, the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method. The dihydrochalcone technical field of organic chemical synthesis technology. Background Art Lourerin B (4 the [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone) made from traditional Chinese medicine Longxuejie separating and extracting a dihydrochalcone. Dihydrochalcone is a very important active ingredient, with anti-oxidation, anti-tumor, anti-diabetic, anti-bacterial and estrogen-like effect. Lourerin B the traditional Chinese medicine has been used for the quality control of the dragon in one of the standard reference material. Through in vitro activity experiment is, prove that it has good promote blood circulation. Wide in application of the product, with very good market prospects. Its structural formula is as follows: By retrieving relevant documentation: found at present, only similar foreign parent structure have been synthesized (Phytochemistry, 27 (6), 1835-1841,1988). In the above-mentioned literature, reported in an aldol condensation reaction at room temperature for 24 hours, after the reaction, separation of the chromatographic column for purification. As Zn catalyst for the reduction of the for generating dihydrochalcone. In the above-mentioned method, long reaction time, the obtained product by column separation, time-consuming, tedious operation. As Zn catalyst for the reduction of, after treatment troublesome. Yet at home and abroad synthetic lourerin B reports. Content of the invention The purpose of this invention is to offer a kind of lourerin B that is, the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalcone synthesis method, in order to overcome the traditional Chinese medicine Longxuejie separating and extracting the content, time-consuming, wastes force, consumption of natural resources. Technical conception of the present invention is such that: in order to 4-benzyloxy acetophenone as the raw material, and then under the action of the potassium hydroxide solution with 2, 4, 6-trimethoxy-aldol condensation formaldehyde, the obtained intermediate in the presence of a catalyst reduction and remove the protecting group, to obtain the target product of the invention lourerin B. Reaction are as follows: The method of the invention uses the raw material 4-benzyloxy acetophenone is reference literature and benzyloxybenzaldehyde Synthesis HL-60 derivatives of anticancer activity against cells.Lin Chin-Fen; Yang Jai-Sing; et al. , Chemistry & Medicinal Bioorganic (2005), 13 (5), 1537-1544. The synthesized by the method reported in. The invention relates to a the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method, which is characterized in that has the following process and steps: A. To 4-benzyloxy acetophenone as raw materials, under the protection of nitrogen in the alcoholic solution of alkali 2, 4, 6-trimethoxy-aldol reaction of formaldehyde, the reaction temperature is the 60-100 [...] , time is 3-16 hours, reaction is ended, the filtered to obtain the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalcone intermediates, raw material 4-benzyloxy acetophenone with 2, 4, 6-trimethoxy-the amount of formaldehyde, the molar ratio of the two the quality of both the 1 [...] the 1-1 [...] 1.2; B. Intermediate of the above-mentioned by the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone placed in the alcoholic solution of alkali, Pd/C the presence of the catalyst under hydrogenation conditions and reduce and remove the protecting group. The temperature of the reduction reaction for the 25-40 [...] , time is 2-8 hours, reaction is ended, is filtered, get the crude product, then recrystallized with ethanol, final to obtain the target product lourerin B that is, the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone. The alcoholic solution of alkali is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and any one of methanol, ethanol, propanol, isopropanol in any one of the preparation of alcoholic solution of alkali, alkali and alcohol volume ratio of the weight of the 1 [...] the 5-1 [...] 10, that is, according to each 1 a gram alkali uses 5-10 ml preparation of alcohol solution of alkali. The above-mentioned raw material 4-benzyloxy acetophenone with the invention the volume ratio the quality of the 1 [...] the 20-1 [...] 50, that is, per 1 gram of raw materials with the 20-50 milliliter mellowness to the proportion of the solution. In the above-mentioned hydrogenation reduction reaction, the proportion of the catalyst it Pd/C a 2%, 5% and 10%, any one of which can be used, according to the amount of catalyst intermediate the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone of the dosage, the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone and the mass ratio of the catalyst consumption Pd/C the 1 [...] 0.5-1 the [...] 2, the conditions of the hydrogenation of the pressure of the hydrogen gas is maintained 5-15mmHg. Specific real-time mode The embodiments of the invention described in the rear. Embodiment 1 In N2 of the three-port in the bottle protection, adding 2.26g (0.01mol) 4-benzyloxy acetophenone, 1.96g (0.01 mol) 2, 4, 6-trimethoxybenzene formaldehyde, add under agitation by the 83 ml propahol and 9.3g (0.16mol) into a solution of KOH. Complete heating reflux, TLC for tracking of the reaction, 3 hours, disappearance of the raw material point. In the reaction process of gradually separate out a large amount of the yellow solid substance, the leach reaction is finished yellow solid, that is, the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, drying to 3.5g, using 50 ml ethanol recrystallization to obtain yellow acicular crystal 3.2 g. Using high performance liquid chromatography to detect the purity is 99% ; yield: 80%. In three-mouth bottle (with mercury seal) adding 1.2g (2.97mmol) the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, 150 ml ethanol is dissolved, add 11.88 ml 1mol/L KOH solution, 0.8g 10% Pd/C catalyst. Magnetic stirring at room temperature, hydrogen gas with hydrogen. Sealing system, control air inlet valve, keeping the mercury 10mmHg. When the mercury seal to maintain mercury in the 30 min is no longer changing, stopping reaction, filtration removing the catalyst. Rotary evaporation of the solvent, crude 0.83g, with 10 ml ethanol re-crystallization. To obtain yellowish crystal 0.8 g. Melting point: 132.2-133 the [...]. Melting point and structure analysis UV-VIS, IR, NMR, MS the various parameters of the extracted from dragon B lourerin of the line of fire. Using high performance liquid chromatography to detect the purity of 99.2%, yield: 85%. Embodiment 2 In N2 of the three-port in the bottle protection, adding 2.26g (0.01mol) 4-benzyloxy acetophenone, 2.15g (0.011mol) 2, 4, 6-trimethoxybenzene formaldehyde, by stirring in 50 ml ethanol and 5.6g (0.1 mol) of KOH solution. Complete heating reflux, TLC for tracking of the reaction, 6 hours, disappearance of the raw material point. In the reaction process of gradually separate out a large amount of the yellow solid substance, the leach reaction is finished yellow solid, that is the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, drying shall 3.4g, using 50 ml ethanol recrystallization to obtain yellow acicular crystal 3.1 g. HPLC: by high performance liquid chromatography to detect the purity of 99.3%, yield: 76.7%. In three-mouth bottle (with mercury seal) adding 1.2g (2.97mmol) the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, 100 ml ethanol is dissolved, adding 11.8 ml NaOH solution lmol/L, 2g 5% Pd/C catalyst. Magnetic stirring at room temperature, hydrogen gas with hydrogen. Sealing system, control air inlet valve, keeping the mercury 15mmHg. When the mercury seal to maintain mercury in the 30 min is no longer changing, stopping reaction, filtration removing the catalyst. Rotary evaporation of the solvent, crude 0.8g, with 10 ml ethanol re-crystallization. To obtain yellowish crystal 0.75 g. Melting point :-132.1 the 132.8 [...]. Melting point and structure analysis UV-VIS, IR, NMR, MS the various parameters of the extracted from dragon B lourerin of the line of fire. Using high performance liquid chromatography to detect the purity is 99%, yield: 80%. Embodiment 3 In N2 of the three-port in the bottle protection, adding 2.26g (0.01mol) 4-benzyloxy acetophenone, 2.35g (0.012 mol) 2, 4, 6-trimethoxybenzene formaldehyde, by stirring in 100 ml ethanol and 16.8g (0.3mol) into a solution of KOH. Heating to complete the 60 [...] , TLC for tracking of the reaction, 15 hours, disappearance of the raw material point. In the reaction process of gradually separate out a large amount of the yellow solid substance, the leach reaction is finished yellow solid, that is, the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, drying shall 3.3g, using 50 ml ethanol recrystallization to obtain yellow acicular crystal 3.15 g. Using high performance liquid chromatography to detect the purity is 99%, yield: 78%. In three-mouth bottle (with mercury seal) adding 1.2g (2.97mmol) the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone, 100 ml ethanol is dissolved, add 18.88 ml 1mol/L NaOH solution, 0.8g 10% Pd/C catalyst. Magnetic stirring at room temperature, hydrogen gas with hydrogen. Sealing system, control air inlet valve, keeping the mercury 5mmHg. When the mercury seal to maintain mercury in the 30 min is no longer changing, stopping reaction, filtration removing the catalyst. Rotary evaporation of the solvent, crude 0.81g, with 10 ml ethanol re-crystallization. To obtain yellowish crystal 0.73 g. Melting point: 132.6-133.4 the UV-VIS [...] melting point and structure analysis, IR, NMR, MS the various parameters of the extracted from dragon B lourerin of the line of fire. Using high performance liquid chromatography to detect the purity of 98.8%, yield: 78%. The invention relates to a method of the preparation of loureirin B i.e. 4' -hydrox-2, 6-trimethoxychalcone, pertaining to the technical field of the chemical synthesis of dihydrochalcone. The invention takes 4-benzyloxy acetophenone as raw material to conduct aldol condensation reaction with 2, 4, 6-trimethoxybenzaldehyde in alkaline alcohol solution to achieve intermediate 4'- benzyloxy-2, 4, 6- trimethoxychalcone; subsequently, the intermediate is added with hydrogen for reduction under the existence of catalyst Pd/C, and de-protecting group, and finally, the desired loureirin B is achieved. The invention provides a method for the chemical synthesis of loureirin B, the operation method is simple and safe, the achieved product has high purity and has activity as high as that of the loureirin B extracted from Longxuejie (Chinese medicine). 1. A the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method, which is characterized in that has the following process and steps: A. To 4-benzyloxy acetophenone as raw materials, under the protection of nitrogen in the alcoholic solution of alkali 2, 4, 6-trimethoxy-aldol reaction of formaldehyde, the reaction temperature is the 60-100 [...] , time is 3-16 hours, reaction is ended, filtered to obtain the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalcone intermediates, raw material 4-benzyloxy acetophenone with 2, 4, 6-trimethoxy-the amount of formaldehyde, the molar ratio of the two the quality of both the 1 [...] the 1-1 [...] 1.2; B. Intermediate of the above-mentioned by the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone placed in the alcoholic solution of alkali, Pd/C the presence of the catalyst under hydrogenation conditions reduce and remove the protecting group, the temperature of the reduction reaction for the 25-40 [...] , time is 2-8 hours, reaction is ended, is filtered, get the crude product, then recrystallized with ethanol, final to obtain the target product lourerin B that is, the 4 [...] -hydroxy -2, 4, 6-trimethyl oxygen radical dihydro chalkone. 2. A the 4 [...] -hydroxy -2 according to Claim 1, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method, characterized in that on the said alkali alcoholic solution of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and any one of methanol, ethanol, propanol, isopropanol in any one of the preparation of alcoholic solution of alkali, alkali and alcohol volume ratio of the weight of the 1 [...] the 5-1 [...] 10, that is, according to each 1 a gram alkali uses 5-10 ml proportion of alcohol to prepare a solution of alkali. 3. A the 4 [...] -hydroxy -2 according to Claim 1, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method, characterized in that the raw material 4-benzyloxy acetophenone with the invention the volume ratio the quality of the 1 [...] the 20-1 [...] 50, that is, per 1 gram of raw materials with the 30-100 milliliter mellowness to the proportion of the solution. 4. A the 4 [...] -hydroxy -2 according to Claim 1, 4, 6-trimethyl oxygen radical dihydro chalkone preparation method, characterized in that the hydrogenation reduction reaction, the proportion of the catalyst it Pd/C a 2%, 5% and 10%, any one of which can be used, according to the amount of catalyst intermediate the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone of the dosage, the 4 [...] -benzyloxy -2, 4, 6-trimethoxy chalkone and the mass ratio of the catalyst consumption Pd/C the 1 [...] 0.5-1 the [...] 2, the conditions for the hydrogenation of the pressure of the hydrogen gas is maintained 5-15mmHg.