CN1827612A - Process for synthesizing daphnetin - Google Patents
Process for synthesizing daphnetin Download PDFInfo
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- CN1827612A CN1827612A CN 200610016731 CN200610016731A CN1827612A CN 1827612 A CN1827612 A CN 1827612A CN 200610016731 CN200610016731 CN 200610016731 CN 200610016731 A CN200610016731 A CN 200610016731A CN 1827612 A CN1827612 A CN 1827612A
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Abstract
The invention provides a new technology for synthesizing daphnetin. It consists of homogeneously mixing pyrogallic acid and malic acid, adding concentrated sulfuric acid, then adding desiccant and organic solvent, agitating slowly and heating-up progressively, pouring them into ice water after the reaction, dispensing, depositing, filtrating, washing the filtered deposition with ice water to neutral phase, and drying to obtain lateritious powder. The invention is excellent in that its reaction condition is moderate, its reaction process can be easily controlled, and it is of few byproducts, high apparent mass and purity of products, and it is easy for refinement. The solid catalyst and organic solvent used in the process can be retrieved and reused, so it can reduce production cost and pollution to the environment. Especially, in relation to the traditional synthetic process, the yield rate and the purity are improved a lot, in which the yield rate increases by more than 30 % and the purity increases to 93 %, so it is more suitable for industrial production.
Description
Technical field
The present invention discloses a kind of novel process of synthetic Daphnetin, has characteristics such as productive rate and purity height, belongs to chemicals synthesis technology field.
Background technology
Daphnetin is one of cardio-cerebrovascular medication, anti-inflammatory, platelet aggregation-against and antithrombotic, vasodilation, increase coronary flow, anti-hypoxia are arranged, improve effect such as myocardial metabolism through pharmacology proof, be used for the treatment of thromboangiitis obliterans and coronary heart disease clinically, and analgesic activity is preferably arranged.Its common name is: Daphnetin, and chemistry is by name: 7, the 8-dihydroxycoumarin, its chemical structure is as follows:
Document (Aust.J., Chem.) synthesis technique of report Daphnetin is to be raw material with pyrogallol and oxysuccinic acid, do to take place under the situation of catalyzer, dewatering agent the Pechman condensation at the vitriol oil and come synthetic, the shortcoming of this method is that productive rate is low, purity is low, the easy charing of raw material, the product visual appearance is poor, and caking phenomenon very easily takes place reaction system.
Summary of the invention
The invention provides a kind of novel process of synthetic Daphnetin, purpose is intended to solve the above-mentioned shortcoming that exists in the traditional synthesis.
Technical solution of the present invention is as follows: existing processes is a catalyzer with the vitriol oil and solid drier on former technology basis, alleviates the charing phenomenon with organic solvent as solvent, synthetic Daphnetin, and its reaction formula is as follows:
The starting raw material pyrogallol that feeds intake in the above-mentioned reaction: oxysuccinic acid weight ratio 1: 0.8～5 is for best.
Reaction system uses the vitriol oil and organic solvent weight ratio 1: 0.2～2.5 to be advisable, and it is slowly suitable to heat up, and temperature of reaction is controlled at 90-140 ℃ for best, and the reaction times should be at 10 minutes-1 hour.
Concrete synthesis technique may further comprise the steps (mark ratio by weight):
Pyrogallol and oxysuccinic acid with 1: 0.8～5 mix, adding and pyrogallol portion rate are 1～10 part the vitriol oil, add again with vitriol oil portion rate be 0.1～10 part siccative and with vitriol oil portion rate be 0.2～2.5 part organic solvent, slowly stir and heat temperature raising 90-140 ℃ gradually, reacted 10～60 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter precipitation through frozen water washing to being neutral, at 105 ℃ of dry brick-red powder.
Above-mentioned siccative can be silica gel, resin, Calcium Chloride Powder Anhydrous, calcium oxide, Vanadium Pentoxide in FLAKES, soda-lime, the vitriol oil, molecular sieve, anhydrous calciumsulphate, anhydrous cupric sulfate, in anhydrous magnesium sulfate, the anhydrous sodium sulphate one or more are mixed, can add fast response and carry out speed.
Above-mentioned organic solvent can be mixed in dioxane, tetracol phenixin, dimethylbenzene, vinyl acetic monomer, butanone, Virahol, butanols, acetone, methylethylketone, cyclohexanone, tetrahydrofuran (THF), toluene, mono chloro benzene, methylene dichloride, the ethylene dichloride one or more, prevents charing.
Synthesis technique of the present invention is compared with traditional synthesis, has following advantage: the reaction conditions gentleness, and the reaction process easy operation control, by product is few, and the visual appearance of product and purity height are easily purified.Used solid catalyst and organic solvent are recyclable in the production utilizes again, thereby has reduced production cost and to the pollution of environment.Particularly compare with traditional synthesis technique, productive rate and purity have had very big raising, and yield can increase more than 30 percentage points, and purity can be increased to and be more suitable for suitability for industrialized production more than 93%.
Following experimental example further proves the product comparative result of production technique of the present invention and traditional processing technology:
Can draw independent use sulfuric acid from above-mentioned comparison test and make catalyzer, yield is between 25-35%, and purity is between the 60-80%, but when sulfuric acid and siccative coupling, yield can increase more than 15 percentage points, and purity can be increased to more than 90%.
Can draw independent use sulfuric acid from above-mentioned comparison test and make catalyzer, yield is between 25-35%, and purity is between the 60-80%, but when sulfuric acid and organic solvent coupling, yield can increase by 20 percentage points, and purity can be increased to more than 90%.
Can draw independent use sulfuric acid from above-mentioned comparison test and make catalyzer, yield is between 25-35%, and purity is between the 60-80%, but when sulfuric acid and siccative, solvent coupling, yield can increase by 30 percentage points, and purity can be increased to more than 93%.
In sum, this technology obviously is better than traditional technology, and can obviously improve yield and purity.
Embodiment:
By following examples the present invention is described for example further, and do not limit the present invention in any way, under the prerequisite that does not deviate from technical solution of the present invention, any change or change that those of ordinary skills that the present invention did are realized easily all will fall within the claim scope of the present invention.
Embodiment 1:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (37.8g) that mixes, oxysuccinic acid (67.5g), with the 75g anhydrous magnesium sulfate, add the 90ml dioxane and the 90ml vitriol oil again, slowly stir and heat temperature raising 100-130 ℃ gradually, reacted 40 minutes, and poured in the frozen water, placed 48 hours, precipitation, filter, filter precipitation through the frozen water washing to being neutral, at 105 ℃ of dry brick-red powder 31.5g, yield is 59%, and purity is 96.3%.
Embodiment 2:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (37.8g) that mixes, oxysuccinic acid (53.6g), with the 45g Vanadium Pentoxide in FLAKES, add the 120ml tetracol phenixin and the 90ml vitriol oil again, slowly stir and heat temperature raising 110-140 ℃ gradually, reacted 1 hour, and poured in the frozen water, placed 48 hours, precipitation, filter, filter precipitation through the frozen water washing to being neutral, at 105 ℃ of dry brick-red powder 35.7g, yield is 66.9%, and purity is 94.2%.
Embodiment 3:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (37.8g) that mixes, oxysuccinic acid (80.4g), with the 100g molecular sieve, add the 160ml tetrahydrofuran (THF) and the 80ml vitriol oil again, slowly stir and heat temperature raising 110-140 ℃ gradually, reacted 1 hour, and poured in the frozen water, placed 48 hours, precipitation, filter, filter precipitation through the frozen water washing to being neutral, at 105 ℃ of dry brick-red powder 30.3g, yield is 56.7%, and purity is 97.6%.
Embodiment 4:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (37.8g) that mixes, oxysuccinic acid (40.2g) with 60g molecular sieve and 50g Calcium Chloride Powder Anhydrous, adds the 110ml toluene and the 100ml vitriol oil again, slowly stir and heat temperature raising 115-125 ℃ gradually, reacted 1 hour, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 37.8g, yield is 70.8%, and purity is 98.3%.
Embodiment 5:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (63g) that mixes, oxysuccinic acid (73.7g) with 60g anhydrous cupric sulfate and 25g silica gel, adds the 160ml vinyl acetic monomer and the 140ml vitriol oil again, slowly stir and heat temperature raising 105-140 ℃ gradually, reacted 30 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 59.8g, yield is 67.2%, and purity is 96.5%.
Embodiment 6:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (63g) that mixes, oxysuccinic acid (89.3g) with the 200g molecular sieve, adds 80ml toluene, 70ml dioxane and the 170ml vitriol oil again, slowly stir and heat temperature raising 90-105 ℃ gradually, reacted 45 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 61.3g, yield is 68.9%, and purity is 95.7%.
Embodiment 7:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (50.4g) that mixes, oxysuccinic acid (103.5g) with the 70g anhydrous sodium sulphate, adds 90ml methylene dichloride, 30ml ethylene dichloride and the 120ml vitriol oil again, slowly stir and heat temperature raising 95-120 ℃ gradually, reacted 25 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 44.1g, yield is 61.9%, and purity is 95.3%.
Embodiment 8:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (63g) that mixes, oxysuccinic acid (107.2g) with 75g resin and 35g calcium oxide, adds the 180ml toluene and the 160ml vitriol oil again, slowly stir and heat temperature raising 115-140 ℃ gradually, reacted 40 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 62.5g, yield is 70.2%, and purity is 94.9%
Embodiment 9:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (37.8g) and the oxysuccinic acid (67g) that mix, add the 100ml dioxane and the 130ml vitriol oil again, slowly stir and heat temperature raising 90-120 ℃ gradually, reacted 50 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 27.1g, yield is 50.7%, and purity is 94.3%.
Embodiment 10:
In three mouthfuls of round-bottomed flasks, add the pyrogallol (50.4g) that mixes, oxysuccinic acid (67g) with the 35g anhydrous cupric sulfate, adds the 140ml vitriol oil again, slowly stir and heat temperature raising 115-140 ℃ gradually, reacted 30 minutes, pour in the frozen water, placed 48 hours, precipitation is filtered, filter to such an extent that precipitation is washed to being neutral through frozen water, at 105 ℃ of dry brick-red powder 30.6g, yield is 43%, and purity is 92.1%.
Claims (4)
1, a kind of novel process of synthetic Daphnetin, may further comprise the steps (by ratio of weight and the number of copies): pyrogallol and oxysuccinic acid with 1: 0.8～5 mix, and add 1～10 part the vitriol oil, and adding and vitriol oil portion rate are 0.2～2.5 part organic solvent again, slowly stir and heat temperature raising 90-140 ℃ gradually, reacted 10～60 minutes, and poured in the frozen water, placed 48 hours, precipitation, filter, filter precipitation through the frozen water washing to being neutral, at 105 ℃ of dry brick-red powder.
2, according to the described production technique of claim 1, it is characterized in that: described organic solvent is that in dioxane, tetracol phenixin, dimethylbenzene, vinyl acetic monomer, butanone, Virahol, butanols, acetone, methylethylketone, pimelinketone, tetrahydrofuran (THF), toluene, mono chloro benzene, methylene dichloride, the ethylene dichloride one or more are mixed.
3, the novel process of synthetic Daphnetin according to claim 1 is characterized in that: with weight ratio is after 1: 0.8～5 pyrogallol and oxysuccinic acid mix, and adding with vitriol oil portion rate is 0.1～10 part siccative.
4, according to the described production technique of claim 3, it is characterized in that: described siccative is silica gel, resin, Calcium Chloride Powder Anhydrous, calcium oxide, Vanadium Pentoxide in FLAKES, soda-lime, the vitriol oil, molecular sieve, anhydrous calciumsulphate, anhydrous cupric sulfate, and one or more in anhydrous magnesium sulfate, the anhydrous sodium sulphate are mixed.
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| CN2006100167310A CN1827612B (en) | 2006-03-31 | 2006-03-31 | Process for synthesizing daphnetin |
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| CN2006100167310A CN1827612B (en) | 2006-03-31 | 2006-03-31 | Process for synthesizing daphnetin |
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