CN103435591B - Chemical synthesis method of piperine - Google Patents
Chemical synthesis method of piperine Download PDFInfo
- Publication number
- CN103435591B CN103435591B CN201310394873.0A CN201310394873A CN103435591B CN 103435591 B CN103435591 B CN 103435591B CN 201310394873 A CN201310394873 A CN 201310394873A CN 103435591 B CN103435591 B CN 103435591B
- Authority
- CN
- China
- Prior art keywords
- piperonyl cyclonene
- piperine
- preparation
- chemical synthesis
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention relates to a chemical synthesis method of piperine, which comprises the following steps: (1) preparation of bromopiperidine; (2) preparation of alpha-p-tolylsulfonylfuran hydrazone; (3) preparation of piperidinyl-alpha-diolefine aldehyde; (4) preparation of piperidinyl-alpha-diolefine acid; and (5) preparation of piperine.In the invention, the piperidine and bromine react to generate the bromopiperidine, so the bromation selectivity is high; and the bromine mainly goes to the beta position of the piperidine, the yield can reach more than 78%, and the byproducts are fewer. The raw materials, including piperidine, bromine, furfural, p-toluenesulfonhydrazide, piperidine and the like are common raw materials in the market, and are easy to purchase and low in price, so that the raw material cost for producing the piperine is much lower than that of other methods.
Description
Technical field
The invention belongs to field of medicine and chemical technology, especially a kind of chemical synthesis process of piperine.
Background technology
Piperine (piperine) belongs to cassia bark phthalein amine alkaloid, has many effects clinically: antibacterial, anti-inflammatory, treatment gastroenteropathy, rheumatic arthritis, wound and nervosa analgesia.Highly purified piperine analgesia injection, all has the severe pain of the generation such as extensive wound and cancer of late stage and significantly subtracts pain curative effect, therefore may be used for tumor aid treatment.Piperine is as a kind of wide spectrum anticonvulsive drug, and in drug rehabilitation, application is also more extensive.Test prove its almost to be addicted to drugs all there is powerful drug treatment function.At home and abroad, particularly South East Asia one is with, and it has been widely used in clinical treatment drug addiction.In addition, piperine is also widely used in the additive of modern pharmaceutical, perfume, makeup, high quality wine and drink food etc.The piperine that current China produces mainly extracts from piper nigrum or white pepper.Pepper is abounded with in the South Asia such as India, Vietnam and south east asia, and China is only in minority southern area plantations such as Guangdong, Guangxis, and cultivated area is limited, so most of pepper raw material needs from external import, thus limits the output of China's piperine.The general extracting method of piperine is after adopting selected pepper dry powder to be broken into pepper powder, carries out lixiviate and obtains soaking body fluid, then go out alcohol through fractionation by distillation, obtain the tan concentrated solution containing piperine with edible ethanol; Carry out crystallization and purification again, obtain the piperine xln that content is higher.In pepper, the content of piperine is generally no more than 10%, and through repeatedly recrystallization after extracting, after reaching the content of more than 99%, its yield is lower.In addition, be subject to the impact of domestic pepper raw material output, the production cost of piperine is at 3000 yuan/more than Kg, and price is at 4000 yuan/about Kg.In recent years, along with the market demand amount of piperine increases, the output of product can not meet the needs in market, and the price of product rises year by year.Increasing enterprise wishes to adopt chemical synthesis to produce highly purified piperine.Synthesis method not by the restriction of pepper raw material, and can increase substantially output, and production cost is more much lower than extraction method.Product can reach the content of more than 99%, and quality meets the needs in market.Namely this patent is adopt chemical synthesis to produce piperine, and is applied in synthesis technique by Huang-min-long dexterously.The reaction of this patent technique is novel, and synthetic route is short, and yield is high, and purity can reach more than 99%, and by product is few, and the pollutent of generation is few, and the raw material of utilization is piperonyl cyclonene cheap and easy to get and furfural, so technique has very strong advance.In addition, the synthesis technique that patent adopts is easy to industrialization, and production capacity is comparatively large, can be good at the demand meeting domestic and international market, makes up the shortcoming that piperine output is subject to raw material impact.
Summary of the invention
The object of the present invention is to provide a kind of chemical synthesis process of piperine.
The present invention is achieved by the following technical solutions:
A chemical synthesis process for piperine, its step is as follows:
(1) preparation of bromo piperonyl cyclonene:
Be dissolved in by piperonyl cyclonene in glacial acetic acid, slowly drip bromine at 0 DEG C in 1h, maintenance temperature of reaction is 0 DEG C, drips and finishes, and continues reaction 2h, washes twice to neutrality with water, obtain product bromo piperonyl cyclonene after drying, for subsequent use;
(2) preparation of α-tolysulfonyl furans hydrazone:
Furfural is dissolved in anhydrous methanol, then adds p-toluene sulfonyl hydrazide, form pale yellow solution, after reacting 2h under normal temperature, reaction solution is poured in frozen water, and place 1h in refrigerator, separate out yellow solid, suction filtration, obtains α-tolysulfonyl furans hydrazone after drying at 100 DEG C of temperature, for subsequent use;
(3) preparation of piperonyl cyclonene-α-diene aldehyde:
Step (1) gained bromo piperonyl cyclonene is added anhydrous tetrahydro furan dilution evenly, obtain bromo piperonyl cyclonene tetrahydrofuran solution, for subsequent use;
Under nitrogen protection, magnesium rod is after treatment added in anhydrous tetrahydro furan, add a small amount of iodine again as initiator, stirring and dissolving, then drip bromo piperonyl cyclonene tetrahydrofuran solution, drip complete reflux 2 hours, until magnesium all dissolves, stop heating, be cooled to room temperature, obtain Grignard reagent, for subsequent use;
Step (2) gained α-tolysulfonyl furans hydrazone is dissolved in anhydrous tetrahydro furan, then the Grignard reagent prepared in advance is at room temperature slowly added drop-wise in the tetrahydrofuran solution of hydrazone, after dropwising, room temperature reaction 2h; The quencher of reacted mixed solution saturated ammonium chloride solution, then be extracted with ethyl acetate, organic layer, through washing twice, finally uses anhydrous magnesium sulfate drying, suction filtration, and filtrate obtains product after revolving steaming, after recrystallization, obtain piperonyl cyclonene-α-diene aldehyde, for subsequent use;
(4) preparation of piperonyl cyclonene-α-diene acid:
Step (3) gained piperonyl cyclonene-α-diene aldehyde is dissolved in the trimethyl carbinol, add the aqueous solution of sodium chlorate and sodium phosphate again, stirring at room temperature reaction 2h, steams after reaction and desolventizes, residuum adds water, divide three extractions with ether, merge ether, with cold wash, dry, steam except ether, obtain piperonyl cyclonene-α-diene acid, for subsequent use;
(5) preparation of piperine:
Sodium methylate is dissolved in methyl alcohol, then adds step (4) gained piperonyl cyclonene-α-diene acid and piperidines, reflux 20 hours.Cooling, reaction mixture is poured into water, and stirs and obtains light yellow solid, and through precipitation, filter, vacuum-drying, recrystallization, obtains piperine finished product.
The weight ratio of the glacial acetic acid in this chemical synthesis process step (1) of a kind of chemical synthesis process of piperine, piperonyl cyclonene, bromine, water is 1:0.3:0.4:1.
The weight ratio of the furfural in this chemical synthesis process step (2) of a kind of chemical synthesis process of piperine, anhydrous methanol, p-toluene sulfonyl hydrazide is 1:23.81:1.86.
The weight ratio of the bromo piperonyl cyclonene in this chemical synthesis process step (3) of a kind of chemical synthesis process of piperine, magnesium rod, anhydrous tetrahydro furan, α-tolysulfonyl furans hydrazone is 1:0.12:7.74:0.87.
The weight ratio of the piperonyl cyclonene-α-diene aldehyde in this chemical synthesis process step (4) of a kind of chemical synthesis process of piperine, the trimethyl carbinol, clorox, sodium phosphate, water, ether is 1:8.26:0.41:0.41:4.1:24.79.
The weight ratio of the piperonyl cyclonene-α-diene acid in this chemical synthesis process step (5) of a kind of chemical synthesis process of piperine, sodium methylate, methyl alcohol, piperidines, α-tolysulfonyl furans hydrazone is 1:0.6:10:3.75.
Advantage of the present invention and beneficial effect are:
1, in the present invention, piperonyl cyclonene and bromine react and generate bromo piperonyl cyclonene, and the selectivity ratios of bromo is higher, and bromine is the upper β position to piperonyl cyclonene mainly, and yield can reach more than 78%, and by product is few.
2, the present invention uses Huang-min-long that the reaction of aldehyde and hydrazine is rested on the stage of hydrazone, activate the aldehyde radical of furfural, be beneficial to the attack of grignard reagent, and then make furan nucleus open loop form diene, the polystep reaction avoided required by other synthetic routes becomes the shortcoming of conjugated dienes, substantially increases the yield of target product.Total recovery can reach 50-60%, is easy to large-scale industrial production.
3, raw material piperonyl cyclonene required for the present invention, bromine, furfural, p-toluene sulfonyl hydrazide, piperidines etc. are easy to buy, and are all that raw material is commonly used in market, and low price, make the raw materials cost that the raw materials cost of production piperine is produced well below additive method.
Embodiment
The present invention is described in further detail by following examples.It should be noted that: following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
Piperonyl cyclonene in the present invention, bromine, furfural, p-toluene sulfonyl hydrazide, piperidines all commercially can be bought and obtain.
Embodiment 1
A chemical synthesis process for piperine, its step is as follows:
(1) preparation of bromo piperonyl cyclonene:
Be dissolved in by piperonyl cyclonene 30g in 100ml glacial acetic acid, slowly drip 40g bromine at 0 DEG C in 1h, maintenance temperature of reaction is 0 DEG C, drips and finishes, and continues reaction 2h, washes twice to neutrality with water, obtain product bromo piperonyl cyclonene 38.7g, yield 78.2% after drying, for subsequent use;
(2) preparation of α-tolysulfonyl furans hydrazone:
Furfural 42g is dissolved in 1000ml anhydrous methanol, then p-toluene sulfonyl hydrazide 78g is added, form pale yellow solution, after reacting 2h under normal temperature, reaction solution is poured in frozen water, and 1h is placed in refrigerator, separate out yellow solid, suction filtration, at 100 DEG C of temperature, obtain α-tolysulfonyl furans hydrazone 103g after drying, yield 92.3%, for subsequent use;
(3) preparation of piperonyl cyclonene-α-diene aldehyde:
Step (1) gained bromo piperonyl cyclonene 32.3g is added the dilution of 100ml anhydrous tetrahydro furan evenly, obtain bromo piperonyl cyclonene tetrahydrofuran solution, for subsequent use;
Under nitrogen protection, magnesium rod 3.9g is after treatment added in 50ml anhydrous tetrahydro furan, add a small amount of iodine again as initiator, stirring and dissolving, then drip bromo piperonyl cyclonene tetrahydrofuran solution, drip complete reflux 2 hours, until magnesium all dissolves, stop heating, be cooled to room temperature, obtain Grignard reagent, for subsequent use;
Step (2) gained α-tolysulfonyl furans hydrazone 28g is dissolved in 100ml anhydrous tetrahydro furan, is more at room temperature slowly added drop-wise in the tetrahydrofuran solution of hydrazone by the Grignard reagent prepared in advance, after dropwising, room temperature reaction 2h; The quencher of reacted mixed solution saturated ammonium chloride solution, then be extracted with ethyl acetate, organic layer is through washing twice, finally use anhydrous magnesium sulfate drying, suction filtration, filtrate obtains product after revolving steaming, piperonyl cyclonene-α-diene aldehyde 27.6g is obtained, yield 85% after recrystallization, for subsequent use;
(4) preparation of piperonyl cyclonene-α-diene acid:
Step (3) gained piperonyl cyclonene-α-diene aldehyde 24.2g is dissolved in the 200ml trimethyl carbinol, then adds the 100ml aqueous solution of 10g sodium chlorate and 10g sodium phosphate, stirring at room temperature reaction 2h, steam after reaction and desolventize, residuum adds 300ml water, divides three extractions with 600ml ether, merges ether, use 100ml cold wash, drying, steams except ether, obtains piperonyl cyclonene-α-diene acid 23.5g, yield 89.8%, for subsequent use;
(5) preparation of piperine:
6g sodium methylate is dissolved in 100m methyl alcohol, add step (4) gained piperonyl cyclonene-α-diene acid 10g and piperidines 37.5g again, reflux 20 hours, cooling, reaction mixture is poured into water, stirring obtains light yellow solid, through precipitation, filters, vacuum-drying, recrystallization, obtains piperine finished product 11.3g, yield 86.2%.
Embodiment 2
A chemical synthesis process for piperine, its step is as follows:
(1) preparation of bromo piperonyl cyclonene:
Piperonyl cyclonene 25g is dissolved in 100ml formic acid, slowly drips 33.3g bromine at-5 DEG C in 1h, maintenance temperature of reaction is-5 DEG C, drips and finishes, and continues reaction 2h, washes twice to neutrality with water, obtain product bromo piperonyl cyclonene 31.1g, yield 75.5% after drying, for subsequent use;
(2) preparation of α-tolysulfonyl furans hydrazone:
Furfural 42g is dissolved in 1000ml dehydrated alcohol, then p-toluene sulfonyl hydrazide 78g is added, form pale yellow solution, after reacting 2h under normal temperature, reaction solution is poured in frozen water, and 1h is placed in refrigerator, separate out yellow solid, suction filtration, at 100 DEG C of temperature, obtain α-tolysulfonyl furans hydrazone 100g after drying, yield 86.6%, for subsequent use;
(3) preparation of piperonyl cyclonene-α-diene aldehyde:
Step (1) gained bromo piperonyl cyclonene 32.3g is added the dilution of 100ml anhydrous diethyl ether evenly, obtain bromo piperonyl cyclonene anhydrous ether solution, for subsequent use;
Under nitrogen protection, magnesium rod 3.9g is after treatment added in 50ml anhydrous diethyl ether, add a small amount of iodine again as initiator, stirring and dissolving, then drip bromo piperonyl cyclonene anhydrous ether solution, drip complete reflux 2 hours, until magnesium all dissolves, stop heating, be cooled to room temperature, obtain Grignard reagent, for subsequent use;
Step (2) gained α-tolysulfonyl furans hydrazone 28g is dissolved in 100ml anhydrous diethyl ether, is more at room temperature slowly added drop-wise in the anhydrous ether solution of hydrazone by the Grignard reagent prepared in advance, after dropwising, room temperature reaction 2h; The quencher of reacted mixed solution saturated ammonium chloride solution, then be extracted with ethyl acetate, organic layer is through washing twice, finally use anhydrous magnesium sulfate drying, suction filtration, filtrate obtains product after revolving steaming, piperonyl cyclonene-α-diene aldehyde 27.6g is obtained, yield 85% after recrystallization, for subsequent use;
(4) preparation of piperonyl cyclonene-α-diene acid:
Step (3) gained piperonyl cyclonene-α-diene aldehyde 25g is dissolved in 200ml Virahol, then adds the 100ml aqueous solution of 10g sodium chlorate and 10g sodium phosphate, stirring at room temperature reaction 2h, steam after reaction and desolventize, residuum adds 300ml water, divides three extractions with 600ml ether, merges ether, use 100ml cold wash, drying, steams except ether, obtains piperonyl cyclonene-α-diene acid 22.1g, yield 81.6%, for subsequent use;
(5) preparation of piperine:
6g sodium methylate is dissolved in 100m ethanol, add step (4) gained piperonyl cyclonene-α-diene acid 10g and piperidines 37.5g again, reflux 40 hours, cooling, reaction mixture is poured into water, stirring obtains light yellow solid, through precipitation, filters, vacuum-drying, recrystallization, obtains piperine finished product 10.2g, yield 77.8%.
Embodiment 3
A chemical synthesis process for piperine, its step is as follows:
(1) preparation of bromo piperonyl cyclonene:
Be dissolved in by piperonyl cyclonene 35g in 100ml glacial acetic acid, slowly drip 46.5g bromine at 10 DEG C in 1h, maintenance temperature of reaction is 10 DEG C, drips and finishes, and continues reaction 2h, washes twice to neutrality with water, obtain product bromo piperonyl cyclonene 45.2g, yield 78.4% after drying, for subsequent use;
(2) preparation of α-tolysulfonyl furans hydrazone:
Furfural 45g is dissolved in 1000ml anhydrous methanol, then p-toluene sulfonyl hydrazide 82g is added, form pale yellow solution, after reacting 2h under normal temperature, reaction solution is poured in frozen water, and 1h is placed in refrigerator, separate out yellow solid, suction filtration, at 100 DEG C of temperature, obtain α-tolysulfonyl furans hydrazone 114.5g after drying, yield 92.5%, for subsequent use;
(3) preparation of piperonyl cyclonene-α-diene aldehyde:
Step (1) gained bromo piperonyl cyclonene 32.3g is added the dilution of 100ml anhydrous tetrahydro furan evenly, obtain bromo piperonyl cyclonene tetrahydrofuran solution, for subsequent use;
Under nitrogen protection, magnesium rod 3.9g is after treatment added in 50ml anhydrous tetrahydro furan, add a small amount of iodine again as initiator, stirring and dissolving, then drip bromo piperonyl cyclonene tetrahydrofuran solution, drip complete reflux 2 hours, until magnesium all dissolves, stop heating, be cooled to room temperature, obtain Grignard reagent, for subsequent use;
Step (2) gained α-tolysulfonyl furans hydrazone 28g is dissolved in 100ml anhydrous tetrahydro furan, is more at room temperature slowly added drop-wise in the tetrahydrofuran solution of hydrazone by the Grignard reagent prepared in advance, after dropwising, room temperature reaction 2h; The quencher of reacted mixed solution saturated ammonium chloride solution, then be extracted with ethyl acetate, organic layer is through washing twice, finally use anhydrous magnesium sulfate drying, suction filtration, filtrate obtains product after revolving steaming, piperonyl cyclonene-α-diene aldehyde 27.6g is obtained, yield 85% after recrystallization, for subsequent use;
(4) preparation of piperonyl cyclonene-α-diene acid:
Step (3) gained piperonyl cyclonene-α-diene aldehyde 25g is dissolved in 200ml ethanol, then adds the 100ml aqueous solution of 10g sodium chlorate and 10g sodium phosphate, stirring at room temperature reaction 2h, steam after reaction and desolventize, residuum adds 300ml water, divides three extractions with 600ml ether, merges ether, use 100ml cold wash, drying, steams except ether, obtains piperonyl cyclonene-α-diene acid 20.8g, yield 77.1%, for subsequent use;
(5) preparation of piperine:
6g sodium methylate is dissolved in 100m methyl alcohol, add step (4) gained piperonyl cyclonene-α-diene acid 10g and piperidines 37.5g again, reflux 20 hours, cooling, reaction mixture is poured into water, stirring obtains light yellow solid, through precipitation, filters, vacuum-drying, recrystallization, obtains piperine finished product 11.3g, yield 86.2%.
Claims (3)
1. a chemical synthesis process for piperine, is characterized in that: the step of this chemical synthesis process is as follows:
(1) preparation of bromo piperonyl cyclonene:
Be dissolved in by piperonyl cyclonene in glacial acetic acid, slowly drip bromine at-5-10 DEG C in 1h, maintenance temperature of reaction is-5-10 DEG C, drips and finishes, and continues reaction 2h, washes twice to neutrality with water, obtain product bromo piperonyl cyclonene after drying, for subsequent use;
(2) preparation of α-tolysulfonyl furans hydrazone:
Furfural is dissolved in anhydrous methanol, then adds p-toluene sulfonyl hydrazide, form pale yellow solution, after reacting 2h under normal temperature, reaction solution is poured in frozen water, and place 1h in refrigerator, separate out yellow solid, suction filtration, obtains α-tolysulfonyl furans hydrazone after drying at 100 DEG C of temperature, for subsequent use;
(3) preparation of piperonyl cyclonene-α-diene aldehyde:
Step (1) gained bromo piperonyl cyclonene is added anhydrous tetrahydro furan dilution evenly, obtain bromo piperonyl cyclonene tetrahydrofuran solution, for subsequent use;
Under nitrogen protection, magnesium rod is after treatment added in anhydrous tetrahydro furan, add a small amount of iodine again as initiator, stirring and dissolving, then drip bromo piperonyl cyclonene tetrahydrofuran solution, drip complete reflux 2 hours, until magnesium all dissolves, stop heating, be cooled to room temperature, obtain Grignard reagent, for subsequent use;
Step (2) gained α-tolysulfonyl furans hydrazone is dissolved in anhydrous tetrahydro furan, then the Grignard reagent prepared in advance is at room temperature slowly added drop-wise in the tetrahydrofuran solution of hydrazone, after dropwising, room temperature reaction 2h; The quencher of reacted mixed solution saturated ammonium chloride solution, then be extracted with ethyl acetate, organic layer, through washing twice, finally uses anhydrous magnesium sulfate drying, suction filtration, and filtrate obtains product after revolving steaming, after recrystallization, obtain piperonyl cyclonene-α-diene aldehyde, for subsequent use;
(4) preparation of piperonyl cyclonene-α-diene acid:
Step (3) gained piperonyl cyclonene-α-diene aldehyde is dissolved in the trimethyl carbinol, add the aqueous solution of sodium chlorate and sodium phosphate again, stirring at room temperature reaction 2h, steams after reaction and desolventizes, residuum adds water, divide three extractions with ether, merge ether, with cold wash, dry, steam except ether, obtain piperonyl cyclonene-α-diene acid, for subsequent use;
(5) preparation of piperine:
Sodium methylate is dissolved in methyl alcohol, then adds step (4) gained piperonyl cyclonene-α-diene acid and piperidines, backflow 20-40 hour, cooling, reaction mixture is poured into water, and stirs and obtains light yellow solid, through precipitation, filters, vacuum-drying, recrystallization, obtains piperine finished product.
2. the chemical synthesis process of piperine according to claim 1, is characterized in that: the weight ratio of the glacial acetic acid in this chemical synthesis process step (1), piperonyl cyclonene, bromine, water is 1:0.3:0.4:1.
3. the chemical synthesis process of piperine according to claim 1, is characterized in that: the weight ratio of the furfural in this chemical synthesis process step (2), anhydrous methanol, p-toluene sulfonyl hydrazide is 1:23.81:1.86.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310394873.0A CN103435591B (en) | 2013-09-03 | 2013-09-03 | Chemical synthesis method of piperine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310394873.0A CN103435591B (en) | 2013-09-03 | 2013-09-03 | Chemical synthesis method of piperine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103435591A CN103435591A (en) | 2013-12-11 |
| CN103435591B true CN103435591B (en) | 2015-07-08 |
Family
ID=49689332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310394873.0A Expired - Fee Related CN103435591B (en) | 2013-09-03 | 2013-09-03 | Chemical synthesis method of piperine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103435591B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110452213B (en) * | 2019-08-02 | 2021-09-17 | 西北大学 | Synthetic method of piperine |
-
2013
- 2013-09-03 CN CN201310394873.0A patent/CN103435591B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| Addition of carbon nucleophiles to aldehyde tosylhydrazones of aromatic and heteroaromatic-compounds: total synthesis of piperine and its analogs;S. Chandrasekhar et al.;《Tetrahedron Letters》;20001231;第41卷;2667-2670 * |
| 窦艳容等.4-溴-1,2-亚甲二氧基苯合成新工艺的研究.《精细化工中间体》.2011,第41卷(第6期),66-68. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103435591A (en) | 2013-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102040606A (en) | Synthetic method of vinpocetine | |
| CN105218621B (en) | Dehydroabietic acid benzimidazole Schiff base heterocyclic derivatives with anti-tumor activity and preparation method therefor and application thereof | |
| CN106977572A (en) | A kind of method using hyodesoxycholic acid as Material synthesis lithocholic acid | |
| CN102875511B (en) | Method for comprehensively extracting dye lignin and kaempferol from sophora fruit | |
| CN103709126B (en) | The synthetic method of the hydroxymethyl tetrahydrofuran of pesticide dinotefuran intermediate 3 | |
| CN103509037B (en) | A kind of clopidogrel and the preparation method of intermediate thereof | |
| CN106243121B (en) | Substituted furan-flavone alcohol derivatives and preparation method thereof | |
| CN103435591B (en) | Chemical synthesis method of piperine | |
| CN103304478B (en) | Alkaloidal intermediate of one class synthesis renieramycins type and preparation method thereof | |
| CN104163786A (en) | Method for preparing 5-methyl-3-bromomethylpyridine hydrobromide | |
| CN109776407B (en) | Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof | |
| CN104710347B (en) | (R) synthetic method of the tetrahydrochysene piperidines of 1 benzyl, 3 methyl 1,2,3,6 | |
| CN110922415A (en) | Synthesis and application of novel anti-tumor active compound | |
| CN104649966A (en) | Method for synthesizing organic intermediate 5-cyano-3-methylpyridine formic acid | |
| CN105111155A (en) | Synthesis method of tert-butyl 4,7-diazaspiro[2.5]octyl-7-formate | |
| CN106866608B (en) | A kind of preparation method of fluoro -3,4- dihydrocoumarin derivative | |
| CN107200763A (en) | A kind of method using chenodeoxycholic acid as Material synthesis lithocholic acid | |
| CN105085267A (en) | Synthetic method for salvianolic acid A | |
| CN105085255B (en) | A kind of synthesis technique of the oxo succinate of 2 alkoxy of imidazolinone herbicide intermediate 3 | |
| CN102977077A (en) | Method for preparing dabigatran etexilate intermediate | |
| CN102993155B (en) | Preparation method of polysubstituted-diarylnaphthopyran photochromic compounds | |
| CN105481814A (en) | Synthetic method for isorhamnetin | |
| CN107629107A (en) | A kind of synthetic method of CDB-2914 | |
| CN108383831A (en) | A kind of preparation method of 4-[(S)-(4-chlorophenyl)-2-pyridinylmethoxy important intermediate | |
| CN106674050B (en) | A kind of synthetic method of benzophenone substituted isoquinoline compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150708 Termination date: 20160903 |