CN102249899A - Process for synthesizing ferulic acid by microwave method - Google Patents
Process for synthesizing ferulic acid by microwave method Download PDFInfo
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- CN102249899A CN102249899A CN2011101179674A CN201110117967A CN102249899A CN 102249899 A CN102249899 A CN 102249899A CN 2011101179674 A CN2011101179674 A CN 2011101179674A CN 201110117967 A CN201110117967 A CN 201110117967A CN 102249899 A CN102249899 A CN 102249899A
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Abstract
The invention discloses a process for synthesizing ferulic acid by a microwave method. According to the method, vanillic aldehyde and malonic acid are used as starting raw materials and are subjected to reactant mixing, a microwave heating reaction, circulating reflux heating, reacting solution transferring, crystallizing by pure water and precipitating, and re-crystallizing to obtain a faint yellow needle-shaped crystal, namely the target compound [3-methoxy-4-hydroxy cinnamic acid]. By utilizing a microwave radiation technology, the reaction is catalyzed by ammonium acetate with low cost, no toxicity and no pollution in the absence of a solvent instead of the common organic bases, such as pyridine and the like, and the ferulic acid can be efficiently and rapidly synthesized in a pollution-free way; and the process conditions and parameters of the synthesis are optimized.
Description
Technical field
The present invention relates to a kind of forulic acid synthesis technique, relate in particular to a kind of microwave method synthetic forulic acid technology, the i.e. synthesis technique under the microwave heating state of [3-methoxyl group-4-hydroxycinnamic acid].
Background technology
Forulic acid, English name ferulic acid, another name An Weina, different name coffic acid, chemical name 3-methoxyl group-4-hydroxycinnamic acid, 2-Propenoic acid, 3-(4-hydroxy-3-methoxyphenl)-chemical name is, the 3-methyl ether, 3-O methyl coffic acid, molecular formula is C
10H
10O
1, structural formula is:
Physical properties: cis and trans two kinds are arranged, and cis is a yellow oil, and trans is square crystallization or fiber crystallization, and molten point is 174 ℃, is dissolved in hot water, and ethanol and ethyl acetate are dissolved in ether slightly, are insoluble in benzene and sherwood oil.
Forulic acid mainly is present in the biomass resources such as Ligusticum wallichii, Radix Angelicae Sinensis, rice bran, wheat bran, be widely used in aspects such as medicine, healthcare products, makeup, has platelet aggregation-against, suppressing the thrombocyte serotonin discharges, suppress the generation of the plain A2 of platelet thrombus (TXA2), strengthen the prostaglandin(PG) activity, analgesia, effects such as alleviating vascular spasm.Be to produce the basic raw material that is used for the treatment of disease medicines such as cardiovascular and cerebrovascular diseases and oligoleukocythemia.As Sodium Ferulate, sharp arteries and veins capsule, Mrs's oral liquid or the like.It has good ultraviolet radiation absorption near the 290nm-330nm simultaneously; and very strong antioxygenation and anti-aging effects arranged; be natural safe free radical quencher and antioxidant; can stimulate the secretion of hormone; and the effect of restraint of tyrosinase arranged; can be absorbed in and to play effect vigorous and graceful and protection skin in the human body, be acknowledged as best natural sun-prevention agent and skin-whitening agents.
At present, forulic acid mainly contains the source of two aspects, is to separate from natural product on the one hand, is synthetic by chemical synthesis process on the other hand.Because the content of forulic acid in natural product is lower, chemical synthesis has been introduced people's common attention.In natural product, separate, mainly be the biomass extractions, this technological operation is loaded down with trivial details, use the strong raw material of multiple corrodibility, and the degree of bad control hydrolysis, cause whole process recovery ratio extremely unstable, and finished product also needs purifying, its key factor is exactly the pros-and-cons type mixture of its forulic acid finished product, and it is higher that it splits cost, and industrial realization cost is very high.
In chemical synthesis, be raw material generally with Vanillin and propanedioic acid, pyridine is a solvent, is catalyzer with piperidines or aniline, prepare by the Knoevenagel-Doebner combined reaction, but this method long reaction time, solvent load is big, and the product recovery rate is low.
At present, the chemical industry synthesis technique of traditional preparation process forulic acid is a raw material with Vanillin and propanedioic acid just, in the condition of salt of wormwood as catalyzer, obtains through the Perkin reaction, and its operational path is as follows:
This arts demand high temperature, the reactivity of its product is lower, and by product is many, and reactant is the pros-and-cons type mixture, also needs to split, and its cost is kept high potential drop and is not got off.
The technology of above-mentioned two kinds of prior aries is difficult to industrialization, causes the market of forulic acid to keep high price and does not have the city, and the industrialization rate is lower.
Summary of the invention
The technical problem to be solved in the present invention provides simple, with low cost, the low pollution of a kind of technology, the synthetic forulic acid technology of microwave method anticorrosive, that do not have harm, and with Vanillin and propanedioic acid starting raw material, concrete steps are as follows:
1. reactant mixes, and Vanillin is mixed with ammonium acetate in propanedioic acid liquid, starts recycle pump, guarantees that reaction mixture speed with 3-25L in continuous recirculation reactor circulates, and gets mixture A1;
2. microwave heating reaction starts microwave reactor, and controlling its frequency is 300MHz～300GHz, and A1 is carried out radiation heating, and temperature of reaction rises 70 ℃ from room temperature, carries reactant A 2;
3. pump around circuit heats, and keeps system temperature at 78-80 ℃, with reactant A 2 pump around circuits reaction 2～6 hours, treats no suspended solid in the system, when becoming homogeneous state liquid and having gas to emit, stops microwave heating, gets reaction solution A3;
4. reaction solution shifts, and continues circulation pump around circuit heating A3, starts cooling system, when reducing by 5～15 ℃, gets reaction solution A4;
5. the pure water crystallization is separated out, and reaction solution A4 is transferred in the eddy current rotation crystallizer, and the guarantee system temperature is to room temperature, through stirring, uses 10 ℃ pure water washing, and crystallization obtains compound A-45;
6. recrystallization, it is to dissolve in 95～98% the ethanol that compound A-45 is transferred to massfraction, add pure water and carry out recrystallization, washing, faint yellow syringe needle crystal, i.e. target compound [3-methoxyl group-4-hydroxycinnamic acid].
Described 1. in, described Vanillin, propanedioic acid, ammonium acetate rate in molar ratio are 1: 2～4: 0.05～0.1.
Described 1. in, described catalyzer can be a pyridine, or piperidines, or ammonium acetate, or carboxylic acid potassium, or triethylamine, or diethylamine, or sodium bicarbonate, or yellow soda ash.
Described 2. in, described microwave heating, the design of its wavelength is at 1～10cm, frequency 300MHz～300GHz, power 400～850W.
Described 2. in, temperature of reaction rises to 70 ℃ from room temperature, room temperature is made a comment or criticism temperature in the normal environment between 12 ℃～25 ℃.
Described 6. in, described ethanol can use methyl alcohol or ethyl acetate.
Compared with prior art, the present invention has the following advantages:
1, owing to directly use reactant to make solvent, reduces the use of solvent, reduced the cost recovery of industrialization, solved the environmental pollution in the industrialization process, most suitable suitability for industrialized production.
2, owing to nontoxic, the free of contamination ammonium acetate alkaline matter of inexpensive thing, substituted conventional pyridine organic bases and made catalyst, thereby avoided using inflammable, explosive, poisonous class chemical substance.
3, owing to adopt the microwave circulating reaction technology, avoid using high temperature, reduce environmental pollution, technological operation is simple, and controllability is strong, and yield is high and stable, is fit to suitability for industrialized production.
4, owing to adopt ethanol to carry out recrystallize, in the process of preparation diacid, utilize the high resolution of forulic acid in ethanol, add cold pure water then, separate out purer forulic acid, avoid numerous and diverse purifying process of prior art, both made the suitable industrialization of technology, avoided the generation of a large amount of solid slag again.
5, owing to adopted confined reaction technology, all kinds of harm of avoiding in the reaction process being produced that human body is caused.
Embodiment
The present invention will be further described below in conjunction with embodiment:
A kind of microwave method of the present invention is synthesized forulic acid technology, and with Vanillin and propanedioic acid starting raw material, concrete steps are as follows:
1. reactant mixes, and Vanillin is mixed with ammonium acetate in propanedioic acid liquid, starts recycle pump, guarantees that reaction mixture speed with 3～25L in continuous recirculation reactor circulates, and gets mixture A1; Wherein the rate in molar ratio of Vanillin, propanedioic acid, ammonium acetate is 1: 2～4: 0.05～0.1; The catalyzer that uses can be a pyridine, or piperidines, or ammonium acetate, or carboxylic acid potassium, or triethylamine, or diethylamine, or sodium bicarbonate, or yellow soda ash.
2. microwave heating reaction starts microwave reactor, and controlling its frequency is 300MHz～300GHz, and wavelength designs at 1～10cm, power 400～850W.A1 is carried out radiation heating, and temperature of reaction rises 70 ℃ from room temperature, carries reactant A 2.
3. pump around circuit heats, and keeps system temperature at 78～-80 ℃, with reactant A 2 pump around circuits reaction 2～6 hours, treats no suspended solid in the system, when becoming homogeneous state liquid and having gas to emit, stops microwave heating, gets reaction solution A3.
4. reaction solution shifts, and continues circulation pump around circuit heating A3, starts cooling system, when reducing by 5～15 ℃, gets reaction solution A4;
5. the pure water crystallization is separated out, and reaction solution A4 is transferred in the eddy current rotation crystallizer, and the guarantee system temperature is to room temperature, through stirring, uses 10 ℃ pure water washing, and crystallization obtains compound A-45;
6. recrystallization, it is to dissolve in 95～98% the ethanol that compound A-45 is transferred to massfraction, add pure water and carry out recrystallization, washing, faint yellow syringe needle crystal, i.e. target compound [3-methoxyl group-4-hydroxycinnamic acid].
Get 500mL exsiccant there-necked flask, add 152g (1mol) Vanillin under the mechanical stirring, the ammonium acetate of 208g (2mol) propanedioic acid and 150mg (0.02mol), shake and evenly put microwave oven into, load onto reflux condensing tube, regulate current control power at 800～1000W, react after 1～1.5 hour, reaction mixture is melt into liquid fully and has gas to emit.
Cold slightly, take out reaction flask, add the 50ml pure water, rolled over same solid after fully stirring, solid is blended suction filtration.Add dehydrated alcohol (100mL, solvent) stirring and add the 500ml pure water after the dissolving fully, separate out solid extremely fully under stirring, suction filtration, filter cake washs with pure water, dry faint yellow syringe needle crystal forulic acid, the 169g altogether of getting.Thick yield: 87%.Mp:174-175 ℃, purity 〉=99% (HPLC).
The present invention adopts microwave irradiation technology, under condition of no solvent, replace conventional organic basess such as pyridine to do this reaction of catalyst with inexpensive nontoxic, free of contamination ammonium acetate, efficiently, fast and contamination-freely synthesized forulic acid, and synthetic processing condition and parameter have been carried out optimum combination.
Claims (6)
1. a microwave method is synthesized forulic acid technology, be characterised in that: this technology may further comprise the steps: 1. reactant mixes, Vanillin is mixed with ammonium acetate in propanedioic acid liquid, start recycle pump, guarantee that reaction mixture speed with 3-25L in continuous recirculation reactor circulates, and gets mixture A1; 2. microwave heating reaction starts microwave reactor, and controlling its frequency is 300MHz～300GHz, and A1 is carried out radiation heating, and temperature of reaction rises 70 ℃ from room temperature, carries reactant A 2; 3. pump around circuit heats, and keeps system temperature at 78-80 ℃, with reactant A 2 pump around circuits reaction 2～6 hours, treats no suspended solid in the system, when becoming homogeneous state liquid and having gas to emit, stops microwave heating, gets reaction solution A3; 4. reaction solution shifts, and continues circulation pump around circuit heating A3, starts cooling system, when reducing by 5～15 ℃, gets reaction solution A4; 5. the pure water crystallization is separated out, and reaction solution A4 is transferred in the eddy current rotation crystallizer, and the guarantee system temperature is to room temperature, through stirring, uses 10 ℃ pure water washing, and crystallization obtains compound A-45; 6. recrystallization, it is to dissolve in 95～98% the ethanol that compound A-45 is transferred to massfraction, add pure water and carry out recrystallization, washing, faint yellow syringe needle crystal target compound [3-methoxyl group-4-hydroxycinnamic acid].
2. a kind of microwave method according to claim 1 is synthesized forulic acid technology, it is characterized in that: described 1. in, described Vanillin, propanedioic acid, ammonium acetate rate in molar ratio are 1: 2～4: 0.05～0.1.
3. a kind of microwave method according to claim 1 is synthesized forulic acid technology, it is characterized in that: described 1. in, described catalyzer can be a pyridine, or piperidines, or ammonium acetate, or carboxylic acid potassium, or triethylamine, or diethylamine, or sodium bicarbonate, or yellow soda ash.
4. a kind of microwave method according to claim 1 is synthesized forulic acid technology, it is characterized in that: described 2. in, described microwave heating, the design of its wavelength is at 1～10cm, frequency 300MHz～300GHz, power 400～850W.
5. a kind of microwave method according to claim 1 is synthesized forulic acid technology, it is characterized in that: described 2. in, temperature of reaction rises to 70 ℃ from room temperature, room temperature is made a comment or criticism temperature in the normal environment between 12 ℃～25 ℃.
6. a kind of microwave method according to claim 1 is synthesized forulic acid technology, it is characterized in that: described 6. in, described ethanol can use methyl alcohol or ethyl acetate.
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| CN2011101179674A CN102249899A (en) | 2011-05-09 | 2011-05-09 | Process for synthesizing ferulic acid by microwave method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116082587A (en) * | 2023-01-30 | 2023-05-09 | 常州工程职业技术学院 | Production process of polyacetal copolymer modified by biological ferulic acid side chain |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1544409A (en) * | 2003-08-19 | 2004-11-10 | 丽珠集团利民制药厂 | Ferulic acid and ferulate preparation method |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1544409A (en) * | 2003-08-19 | 2004-11-10 | 丽珠集团利民制药厂 | Ferulic acid and ferulate preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 何良波: "微波辅助阿魏酸合成的工艺研究", 《石河子大学学报》 * |
| 程青芳: "无溶剂下微波辐射合成阿魏酸", 《日用化学工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116082587A (en) * | 2023-01-30 | 2023-05-09 | 常州工程职业技术学院 | Production process of polyacetal copolymer modified by biological ferulic acid side chain |
| CN116082587B (en) * | 2023-01-30 | 2024-02-09 | 常州工程职业技术学院 | Production process of polyacetal copolymer modified by biological ferulic acid side chain |
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Application publication date: 20111123 |