CN103910615A - Method for synthesizing curcumin - Google Patents
Method for synthesizing curcumin Download PDFInfo
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- CN103910615A CN103910615A CN201410140444.5A CN201410140444A CN103910615A CN 103910615 A CN103910615 A CN 103910615A CN 201410140444 A CN201410140444 A CN 201410140444A CN 103910615 A CN103910615 A CN 103910615A
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- curcumine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
Abstract
The invention discloses a method for synthesizing curcumin, and belongs to the technical field of chemical synthesis. According to the technical scheme, the method comprises the following steps: fully and uniformly stirring vanillic aldehyde, acetylacetone, tributyl borate and N, N-dimethylformamide at the temperature of 40-45 DEG C to obtain a boric anhydride-protected acetylacetone complex; dropwise adding a catalyst, namely, n-butylamine to continue reacting; and finally, adding acetic acid for damaging the complex into the reaction system to obtain crude curcumin. The synthetic method is wide in raw material source, and easy to operate; the reaction energy consumption is low since the heating reaction temperature is low (40-45 DEG C), and the crude curcumin can be synthesized by adding acetic acid for damaging the complex after the catalyst, namely, n-butylamine, is dropwise added for reacting; the number of reaction steps is small, and the process route is simplified, so that the deterioration rate is low, and the product yield is increased by about 20 percent than that of the prior art; the reaction conditions are easy to meet and control, and the method is environment-friendly and suitable for industrial mass production.
Description
Technical field
The invention belongs to chemosynthesis technical field, be specifically related to a kind of method of synthetic curcumine.
Background technology
Curcumine (curcumin) is a kind of phenol pigment extracting from Zingiber curcuma turmeric rhizome, and the structure of this compound is as follows:
Curcumine has important economic worth and pharmacological action widely.As anti-oxidant, anti-inflammatory, atherosclerosis, reducing blood-fat etc.; Curcumine is widely applied to (E100) in foodstuffs industry as a kind of natural pigment.It is stable to reductive agent, strong coloring force, and not fugitive color, but to light, heat and iron ion sensitivity.Be mainly used in the dyeing of can, intestines based article, sauce spiced and stewed food.There is report to point out that curcumine is effective anti-mutation agent, can inducing cell cycle arrest and apoptosis, be a kind of very promising antitumour drug.
Curcumine obtained by synthetic method in 1910, and had determined its chemical structure, but building-up reactions needs eight steps, and productive rate is very low.Existing synthetic method craft route complexity, yield is low, and synthetic curcumine content do not reach requirement, and the pollution to environment in building-up process is larger, is therefore not suitable for amplifying on a large scale production application.
Summary of the invention
In order to overcome the defect existing in above-mentioned prior art, the object of the present invention is to provide a kind of method of synthetic curcumine, the method is simple to operate, environmental friendliness, yield is high, and the curcumine content being synthesized by the method is high.
The present invention is achieved through the following technical solutions:
A kind of method of synthetic curcumine; by Vanillin, methyl ethyl diketone, tri-n-butyl borate and N; N dimethyl formamide; at 40～45 ℃; stir, obtain the acetylacetonate complex of boron trioxide protection, be then added dropwise to catalyzer n-Butyl Amine 99 and continue reaction; in the most backward reaction system, add the acetic acid for destroying complex compound, obtain curcumine crude product.
Also comprise the step of with ethanol, curcumine crude product being carried out recrystallization, make curcumine sterling.
A method for synthetic curcumine, comprises the following steps:
1) press 1:(5～10): (0.4～0.6): (1～2): the mol ratio of (0.2～2), get Vanillin, N, N dimethyl formamide, methyl ethyl diketone, tri-n-butyl borate and n-Butyl Amine 99, by Vanillin, N, N dimethyl formamide, methyl ethyl diketone and tri-n-butyl borate add in reaction vessel, at 40～50 ℃, after stirring reaction 1～2h, drip n-Butyl Amine 99, continue reaction 2～5h;
2) be 5%～10% acetum to dripping while stirring 100～200mL massfraction in reaction system, after separating out red solid, continue to stir 1～3h, then suction filtration, washing filter residue, obtains curcumine crude product.
Also comprise the step of with ethanol, curcumine crude product being carried out recrystallization, concrete operations are: the curcumine crude product alcohol heating reflux making is processed to 1～2h, be then cooled to room temperature, reaction solution suction filtration is obtained to filter residue, residue washing post-drying, obtains faint yellow solid, i.e. curcumine sterling.
When reflux is processed, the amount ratio of curcumine crude product and ethanol is 1g:(3～5mL).
Adopt washing with alcohol filter residue.
The massfraction of described ethanol is 30%～50%.
The temperature of reflux is 50～80 ℃.
The temperature that filter residue is dried is 50～65 ℃.
Compared with prior art, the present invention has following useful technique effect:
The method of the synthetic curcumine of the present invention; by Vanillin, methyl ethyl diketone, tri-n-butyl borate and N; after N dimethyl formamide mixes; under heating condition, stir; obtain the acetylacetonate complex of boron trioxide protection; then be added dropwise to catalyzer n-Butyl Amine 99, in the most backward system, add acetic acid to destroy complex compound, thereby make curcumine crude product.Synthetic method raw material sources of the present invention are extensive, simple to operate; Reacting by heating temperature low (40～45 ℃), thereby energy consumption of reaction is low, drips after the reaction of catalyzer n-Butyl Amine 99, adds acetic acid to destroy complex compound and just can synthesize and obtain curcumine crude product; It is few that step is gone through in reaction, and operational path is simplified, thereby damage rate is low, and product yield improves approximately 20% compared with prior art; Do not re-use boron oxide, cost is lower; Reaction conditions easily meets easy to control, and environmental friendliness is applicable to industrial amplification production.
Accompanying drawing explanation
Fig. 1 is the nucleus magnetic hydrogen spectrum of the curcumine that makes of the present invention;
Fig. 2 is the HPLC figure of the curcumine that makes of the present invention.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, and the explanation of the invention is not limited.
Embodiment 1
A method for synthetic curcumine, comprises the following steps:
1) in clean clean reactor, drop into 0.10mol Vanillin, 0.5molN, N dimethyl formamide, 0.04mol methyl ethyl diketone and 0.10mol tri-n-butyl borate, at 50 ℃, after stirring reaction 1h, drip 0.02mol n-Butyl Amine 99, insulation reaction 2h;
2) be 5% acetum to dripping while stirring 100mL massfraction in reaction system, after separating out red crystals, continue to stir 2h, then suction filtration, washing filter residue, obtains curcumine crude product;
3) press the amount ratio of 1g:3mL, the ethanol that is 50% by the curcumine crude product massfraction making reflux at 60 ℃ is processed 1～2h, then be cooled to room temperature, reaction solution suction filtration is obtained to filter residue, after residue washing, at 50 ℃, dry, obtain faint yellow solid, i.e. curcumine sterling, purity reaches 99.1%, and productive rate is 71.3%.
Referring to Fig. 1, for the curcumine nucleus magnetic hydrogen spectrum that the present invention makes, prove by analysis, be curcumine, nuclear magnetic data
1h-NMR (DMSO-d
6) and resolve as shown in table 1:
The curcumine nucleus magnetic hydrogen spectrum data that table 1 the present invention makes
| Node | Shift | ? | Comment |
| CH 3 | 3.841 | 6H | methyl |
| H | 6.060 | 1H | ethylene |
| CH | 6.745 | 1H | benzene |
| CH | 6.784 | 1H | benzene |
| CH | 6.817 | 1H | benzene |
| CH | 6.837 | 1H | benzene |
| CH | 7.145 | 1H | benzene |
| CH | 7.168 | 1H | benzene |
| H | 7.328 | 2H | ethylene |
| H | 7.531 | 1H | ethylene |
| H | 7.569 | 1H | ethylene |
| OH | 9.679 | 2H | aromatic?C-OH |
| OH | 16.435 | 1H | enol |
Embodiment 2
A method for synthetic curcumine, comprises the following steps:
1) in clean clean reactor, drop into 0.10mol Vanillin, 0.8molN, N dimethyl formamide, 0.05mol methyl ethyl diketone and 0.15mol tri-n-butyl borate, at 45 ℃, after stirring reaction 2h, drip 0.08mol n-Butyl Amine 99, insulation reaction 4h;
2) be 8% acetum to dripping while stirring 140mL massfraction in reaction system, after separating out red crystals, continue to stir 1h, then suction filtration, washing filter residue, obtains curcumine crude product;
3) press the amount ratio of 1g:4mL, the ethanol that is 40% by the curcumine crude product massfraction making reflux at 50 ℃ is processed 1～2h, then be cooled to room temperature, reaction solution suction filtration is obtained to filter residue, after residue washing, at 55 ℃, dry, obtain faint yellow solid, i.e. curcumine sterling, purity reaches 99.3%, and productive rate is 69.6%.
Embodiment 3
A method for synthetic curcumine, comprises the following steps:
1) in clean clean reactor, drop into 0.10mol Vanillin, 1.0molN, N dimethyl formamide, 0.06mol methyl ethyl diketone and 0.20mol tri-n-butyl borate, at 40 ℃, after stirring reaction 2h, drip 0.20mol n-Butyl Amine 99, insulation reaction 5h;
2) be 10% acetum to dripping while stirring 200mL massfraction in reaction system, after separating out red crystals, continue to stir 3h, then suction filtration, washing filter residue, obtains curcumine crude product;
3) press the amount ratio of 1g:5mL, the ethanol that is 30% by the curcumine crude product massfraction making reflux at 80 ℃ is processed 1～2h, then be cooled to room temperature, reaction solution suction filtration is obtained to filter residue, after residue washing, at 65 ℃, dry, obtain faint yellow solid, i.e. curcumine sterling, purity reaches 99.0%, and productive rate is 72.4%.
Referring to Fig. 2, the curcumine making for the present invention and the HPLC collection of illustrative plates of curcumine reference substance, testing conditions is as follows: chromatographic column is: C18(4.6mm × 250mm, 5 μ m), column temperature: 30 ℃; Moving phase: methyl alcohol: water: phosphoric acid (60:40:0.5%) v/v; Sample size 10 μ l; Flow velocity: 1.0ml/min detects wavelength: 420nm.
Wherein, 1,2 is reference substance, 3, the 4 curcumine products that make for the present invention, as can be seen from the figure, and the curcumine that the present invention makes and the appearance time of reference substance, peak type, peak area is all close.
In sum, the method for the synthetic curcumine of the present invention, simple to operate, the order in no particular order that feeds intake, directly adds raw material, is easy to suitability for industrialized production; Product yield significantly improves, than synthetic method raising in the past 20%; Approach the low yield of room temperature reaction energy consumption high; Add 5% acetic acid to destroy complex compound and obtain curcumine crude product, effectively reduce contaminated wastewater; Product content is higher, can reach more than 98% through simple process.
Claims (9)
1. the method for a synthetic curcumine; it is characterized in that; by Vanillin, methyl ethyl diketone, tri-n-butyl borate and N; N dimethyl formamide, at 40～45 ℃, stirs; obtain the acetylacetonate complex of boron trioxide protection; then be added dropwise to catalyzer n-Butyl Amine 99 and continue reaction, in the most backward reaction system, add the acetic acid for destroying complex compound, obtain curcumine crude product.
2. the method for a kind of synthetic curcumine according to claim 1, is characterized in that, also comprises the step of with ethanol, curcumine crude product being carried out recrystallization, makes curcumine sterling.
3. the method for a kind of synthetic curcumine according to claim 1, is characterized in that, comprises the following steps:
1) press 1:(5～10): (0.4～0.6): (1～2): the mol ratio of (0.2～2), get Vanillin, N, N dimethyl formamide, methyl ethyl diketone, tri-n-butyl borate and n-Butyl Amine 99, by Vanillin, N, N dimethyl formamide, methyl ethyl diketone and tri-n-butyl borate add in reaction vessel, at 40～50 ℃, after stirring reaction 1～2h, drip n-Butyl Amine 99, continue reaction 2～5h;
2) be 5%～10% acetum to dripping while stirring 100～200mL massfraction in reaction system, after separating out red solid, continue to stir 1～3h, then suction filtration, washing filter residue, obtains curcumine crude product.
4. the method for a kind of synthetic curcumine according to claim 3, it is characterized in that, also comprise the step of with ethanol, curcumine crude product being carried out recrystallization, concrete operations are: the curcumine crude product alcohol heating reflux making is processed to 1～2h, then be cooled to room temperature, reaction solution suction filtration is obtained to filter residue, residue washing post-drying, obtain faint yellow solid, i.e. curcumine sterling.
5. the method for a kind of synthetic curcumine according to claim 4, is characterized in that, when reflux is processed, the amount ratio of curcumine crude product and ethanol is 1g:(3～5mL).
6. the method for a kind of synthetic curcumine according to claim 4, is characterized in that, adopts washing with alcohol filter residue.
7. according to the method for a kind of synthetic curcumine described in claim 4 or 5 or 6, it is characterized in that, the massfraction of described ethanol is 30%～50%.
8. according to the method for a kind of synthetic curcumine described in claim 4 or 5, it is characterized in that, the temperature of reflux is 50～80 ℃.
9. the method for a kind of synthetic curcumine according to claim 4, is characterized in that, the temperature that filter residue is dried is 50～65 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410140444.5A CN103910615A (en) | 2014-04-09 | 2014-04-09 | Method for synthesizing curcumin |
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| CN201410140444.5A CN103910615A (en) | 2014-04-09 | 2014-04-09 | Method for synthesizing curcumin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106748705A (en) * | 2016-12-23 | 2017-05-31 | 杭州瑞树生化有限公司 | A kind of method of artificial synthesized curcumin and its derivative |
| CN108101761A (en) * | 2017-12-08 | 2018-06-01 | 陕西嘉禾生物科技股份有限公司 | A kind of preparation method of curcumin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101454267A (en) * | 2006-03-29 | 2009-06-10 | 帝斯曼知识产权资产管理有限公司 | Curcumin synthesis |
| CN102911022A (en) * | 2012-10-25 | 2013-02-06 | 山东鲁诺动物药业有限公司 | Method for artificially synthesizing natural curcumin compound |
-
2014
- 2014-04-09 CN CN201410140444.5A patent/CN103910615A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101454267A (en) * | 2006-03-29 | 2009-06-10 | 帝斯曼知识产权资产管理有限公司 | Curcumin synthesis |
| CN102911022A (en) * | 2012-10-25 | 2013-02-06 | 山东鲁诺动物药业有限公司 | Method for artificially synthesizing natural curcumin compound |
Non-Patent Citations (3)
| Title |
|---|
| H.J.J.PABON: "A SYNTHESIS OF CURCUMIN AND RELATED COMPOUNDS", 《RECUEIL》, vol. 83, 31 December 1964 (1964-12-31), pages 379 - 386 * |
| 国大亮等: "天然姜黄素类化合物的合成", 《药学研究》, vol. 32, no. 3, 31 December 2013 (2013-12-31), pages 125 - 127 * |
| 邹春阳等: "天然产物姜黄素合成工艺研究", 《中华中医药学刊》, vol. 29, no. 9, 30 September 2011 (2011-09-30), pages 2101 - 2103 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106748705A (en) * | 2016-12-23 | 2017-05-31 | 杭州瑞树生化有限公司 | A kind of method of artificial synthesized curcumin and its derivative |
| CN106748705B (en) * | 2016-12-23 | 2020-05-05 | 杭州瑞树生化有限公司 | Method for artificially synthesizing curcumin and derivatives thereof |
| CN108101761A (en) * | 2017-12-08 | 2018-06-01 | 陕西嘉禾生物科技股份有限公司 | A kind of preparation method of curcumin |
| CN108101761B (en) * | 2017-12-08 | 2021-08-03 | 陕西嘉禾生物科技股份有限公司 | Preparation method of curcumin |
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Application publication date: 20140709 |