CN1041302C - Synthesis for high purity beta ionone - Google Patents
Synthesis for high purity beta ionone Download PDFInfo
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- CN1041302C CN1041302C CN94116569A CN94116569A CN1041302C CN 1041302 C CN1041302 C CN 1041302C CN 94116569 A CN94116569 A CN 94116569A CN 94116569 A CN94116569 A CN 94116569A CN 1041302 C CN1041302 C CN 1041302C
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Abstract
The present invention discloses a method for synthesizing high-purity beta-ionone from citral, which comprises two steps that firstly, a clasien-Schmidt condensation reaction of citral and propanone is carried out in strong alkali liquor under the action of phase transfer to synthesize pseudoionone; secondly, concentrated sulphuric acid is used as a cyclizing agent to cyclize the pseudoionone to produce beta-ionone. The content of the beta-ionone in synthetic products of the present invention is higher than 96%, the content of alpha-ionone is lower than 1%, or even no alpha-ionone exists. Moreover, the method of the present invention is simple and easy to operate, and has no specific requirements for equipment. The obtained product beta-ionone not only can be used as a perfume raw material, but also is an important intermediate body for synthesizing vitamin A in pharmaceutical industry.
Description
The invention belongs to flavor chemistry and medicine industry field, relate to the preparation of intermediate product in a kind of synthetic method of violet aromatic compound and the process.
Jononeionone is the synthetic perfume of a quasi-tradition.Wherein alpha, beta-lonone also has an important purposes except that making spices usefulness, is exactly as synthesise vitamins A (V
A) the synthetic of important intermediate alpha, beta-lonone finish through the reaction of two steps usually, at first be that citral and acetone the Claisen-Schmidt condensation reaction takes place under alkaline condition obtain the intermediate pseudo ionone; Cyclization takes place in pseudo ionone in acidic medium, generate alpha, beta-lonone and isomer α-Zi Luolantong
Citral acetone pseudo ionone alpha, beta-lonone α-Zi Luolantong
At two reaction process of synthetic alpha, beta-lonone, relevant in recent years research report is also many, and the method for synthetic pseudo ionone is under the catalysis of highly basic such as sodium hydroxide, potassium hydroxide, hydrated barta etc. at first, makes solvent with methyl alcohol or ethanol.But condensation product with this understanding is often very complicated, because in highly basic, complicated condensation reaction also can take place in citral and citral, citral and pseudo ionone, pseudo ionone and pseudo ionone, generate high boiling material, product postprocessing difficulty and yield are lower.Some propositions of improving one's methods are as making catalyzer [Paul A Vatakencherry, Chemistry and Industry 2 March 1987, P163-164 with alkaline aluminium or alkali alumina; Wang Qiuan " chemistry world " 1991, No.10, P449-451]; Make catalyzer [CN1065471A with strong anion-exchange resin; Zhang Nengfang " ion-exchange and absorption " 1,991 7 (2) 142-146], compare with the method for highly basic catalyzing and condensing, the purity of pseudo ionone and productive rate all obviously improve, and it is simple to operate, but common shortcoming be exactly in the reaction process catalyst levels big, the recycling complicated operation needs to use a large amount of organic solvent washings, brings difficulty to suitability for industrialized production.
Can see that from the reaction of front the product that generates after the pseudo ionone cyclisation is two kinds of jononeionone isomer, and at synthetic V
AProcess in, the purity of alpha, beta-lonone is to final V
AQuality influence very big, international standard is to being used for synthetic V
AThe purity of alpha, beta-lonone regulation is arranged, i.e. β-position 〉=95%, alpha-position≤2%.The high-content of the alpha, beta-lonone of domestic production producer only is 88%, and major cause is that the acetic acid that adopt are made cyclizing agent more, and is acid on the weak side, and temperature of reaction is higher, and generally more than 25 ℃, these all have a strong impact on the content of β-position in the product.United States Patent (USP) U.S.P 4,55,894, propose on the basis of various researchs in early days further to improve, the continuous production processes of alpha, beta-lonone is disclosed, adopt the thin film evaporation reactor, make the content of alpha, beta-lonone reach 9%, be higher than 2%, this cyclization process equipment requirements height more but wherein the content of α-Zi Luolantong is also, complicated operation, industrialization has certain degree of difficulty.
The objective of the invention is to propose high purity alpha, beta-lonone that a kind of suitability for industrialized produces and as the synthesis technique of intermediate pseudo ionone.
Realization of the present invention is divided into two parts.
First part is to be raw material with citral and acetone, and the Claisen-Schmidt condensation reaction takes place the effect by phase-transfer catalyst in strong base solution, generates pseudo ionone.
In the reaction, the mol ratio of citral and acetone is 1: 1-1: 10, preferably 1: 5-1: 9, citral adds with the mode that drips, 0.5-1.5 hour dropping time, preferably 1 hour, and keep the temperature 4 '-thiobis (the 6-tertiary butyl) meta-cresol, three-(3, the 5-di-tert-butyl-hydroxy phenyl) isocyanuric acid ester, 1,3-dimethylbutyl-N-phenyl-to benzyl diamines, N-phenyl-N '-sec.-propyl-Ursol D, 6-oxyethyl group-2,2,4-trimethylammonium-1,2 ,-dihyaroquinoline, antioxidant 1076, antioxidant 1010, antioxidant D NP, antioxidant 4010 etc.
Reacting used aqueous alkali can be sodium hydroxide, potassium hydroxide, also can be the mixture of yellow soda ash and sodium hydroxide, yellow soda ash and potassium hydroxide.Concentration of lye is better in 1～10% effect, and preferably 3～8%.
Need not cooling after reaction finishes, add the acetum neutralization, reclaim acetone then, it is refining that the thick pseudo ionone that obtains is carried out underpressure distillation.The highest yield of this step can be up to 91%, and through gas chromatographic analysis, its content is more than 98%.
Second section of the present invention is that cyclization takes place in acid pseudo ionone, synthetic alpha, beta-lonone.The key of reaction is to control that reaction conditions improves the alpha, beta-lonone content in the product as far as possible and the content that reduces α-Zi Luolantong.
The present invention is cyclizing agent with the vitriol oil, and vitriol oil concentration is 95-98%, and consumption is 1～5 times (by weight) of pseudo ionone, preferably 2.5～4.5 times.
The present invention requires to carry out at low temperatures, temperature of reaction is advisable with-20 ℃～20 ℃, be preferably in-18 ℃～10 ℃, make like this and form stable milk sap in the reaction process, both avoided local reaction overheated, and caused α-Zi Luolantong content to increase, and also avoided pseudo ionone to issue green resinization simultaneously in vitriol oil effect, high boiling material is increased, and product yield reduces.
The present invention makes solvent with proportion greater than 1.0 chlorinated hydrocarbon, solvent load is 3～5 times (weight meters) of pseudo ionone, the material that can be used as solvent is: orthodichlorobenzene, monochloroethane, 1,2-ethylene dichloride, methylene dichloride, trichloromethane, trifluorochloromethane, 1, tetracol phenixin, it also can be their mixture, wherein preferentially select 1 for use.
For the yield that improves β in the product-position product and prevent that β-position from transforming to alpha-position, the present invention has added transposition and has prevented agent in the cyclization process, effect is preferably the benzophenone compound of absorbing wavelength more than 230nm, comprise 2-hydroxyl-4-methoxy benzophenone, 2-hydroxyl-4-octyloxy benzophenone, 2-hydroxyl-4-oxygen in last of the ten Heavenly stems base benzophenone, 2-hydroxyl-4-dodecyl benzophenone or 2,2 '-dihydroxyl-4,4 '-dimethoxy-benzophenone etc., this transposition prevents that the consumption of agent from being 0.01～1.0% (mol ratio) of pseudo ionone.
Another characteristics of the present invention are to adopt vitriol to make emulsion splitter.The reaction mixture dilution must be hydrolyzed after reaction finishes, but mixture formed the very big milk sap of viscosity this moment, and agitator is obstructed, must add emulsion splitter, the consumption of emulsion splitter is 0.1～1.0 times of sulfuric acid amount.Available vitriol comprises Tai-Ace S 150, sodium sulfate or blue vitriol etc., and concentration is 10～30%.The sulfur waste acid and corresponding metal, metallic compound or oxyhydroxide prepared in reaction of discharging during these vitriol can be used and produce.
The cyclization time is 1.5～2 hours.
The total recovery in second step of the present invention is up to 87.0%, and through gas chromatographic analysis and ultraviolet spectrophotometry analysis, alpha, beta-lonone content can be higher than 96%, and α-Zi Luolantong content is lower than 1%.
Accompanying drawing one, two is respectively the infrared spectrogram and the gas chromatogram of alpha, beta-lonone.
The easily row that is easy to implement of the present invention.The initial feed citral can be from natural perfume litsea cubeba oil.China's litsea cubeba oil aboundresources also is producing country the biggest in the world and export State, so raw material is easy to get, and entire synthesis process does not have special requirement to equipment.The process of synthetic pseudo ionone adds phase-transfer catalyst and condensation inhibitor and control reaction temperature, makes to be reflected under the optimal conditions and finishes, also be simultaneously second the step the synthetic of alpha, beta-lonone lay the first stone.In cyclization, control low temperature (20 ℃～20 ℃) effectively, and solvent, transposition prevent that selecting for use of agent and emulsion splitter from all being to realize key link of the present invention.In a word, in the final product of the present invention, alpha, beta-lonone purity height, and just trace existence of α-Zi Luolantong is the synthetic V of pharmaceutical industry
AImportant material is provided.
The present invention also is applicable to methylionone, particularly important perfume material isoraldeine synthetic.
The present invention is further illustrated below by embodiment.
Embodiment one
Acetone 180.0g, water 200.0g, potassium hydroxide 4.5g, antioxidant 1010 4.0g, Polyethylene Glycol-600 6.0g are added one to be had in the 1000ml there-necked flask of thermometer, dropping funnel, start agitator, the conditioned reaction liquid temp is 30 ℃, drip the 100.0g citral while stirring, the control rate of addition dropwised in 1 hour, continue to stir and be warming up to 40 ℃, kept this temperature stirring reaction 2 hours.Add acetate and be neutralized to PH=7, standing demix is told the upper strata oil reservoir and is carried out underpressure distillation, collects 118～124 ℃/533Pa of cut, obtains pseudo ionone product 115.2g, yield 91.0%,
The cyclization time is 1.5-2 hour.
The total recovery in second step of the present invention is up to 87.0%, and through gas chromatographic analysis and ultraviolet spectrophotometry analysis, alpha, beta-lonone content can be higher than 96%, and α-Zi Luolantong content is lower than 1%.
Figure one, two is respectively the gas chromatogram and the infrared spectrogram of alpha, beta-lonone.
The easily row that is easy to implement of the present invention, the initial feed citral can be from natural perfume litsea cubeba oil, China's litsea cubeba oil aboundresources, also be producing country the biggest in the world and export State, therefore raw material is easy to get, and entire synthesis process does not have special requirement to equipment, and the process of synthetic pseudo ionone adds phase-transfer catalyst and condensation inhibitor and control reaction temperature, make to be reflected under the optimal conditions and finish, simultaneously also be second the step the synthetic of alpha, beta-lonone lay the first stone.In cyclization, control low temperature (20-20 ℃) effectively, and solvent, transposition prevent that selecting for use of agent and emulsion splitter from all being to realize key link of the present invention.In a word, in the final product of the present invention, alpha, beta-lonone purity height, and just trace existence of α-Zi Luolantong is the synthetic V of pharmaceutical industry
AImportant material is provided.
The present invention also is applicable to the synthetic of the particularly important perfume material isoraldeine of methylionone
The present invention is further illustrated below by embodiment.
Embodiment one
With acetone 180.0g, water 200.0g, potassium hydroxide 4.5g, antioxidant 1010 4.0g, Polyethylene Glycol-600 6.0g adds one and has thermometer, in the 1000ml there-necked flask of dropping funnel, start agitator, the conditioned reaction liquid temp is 30 ℃, drip the 100.0g citral while stirring, the control rate of addition dropwised in 1 hour, continued to stir and be warming up to 40 ℃, kept this temperature stirring reaction 2 hours.Add acetate and be neutralized to PH=7, standing demix is told the upper strata oil reservoir and is carried out underpressure distillation, collects 118-124 ℃/533Pa of cut, obtains pseudo ionone product 115.2g, yield 91.0%, N
d 20: 1.5331.
Embodiment two
Acetone 800kg, water 1200kg, sodium hydroxide 120.0g, cetyl trimethylammonium bromide 38kg drops into reactor, start stirrer and regulate 20 ℃ of water temperatures, Dropwise 5 00kg citral and 10kg 6-oxyethyl group-2 while stirring, 2, the mixture of 4-trimethylammonium-1,2 dihyaroquinoline, be controlled in 1 hour and dropwise, continue to stir and made temperature of charge be raised to 30 ℃ in 0.5 hour, continue reaction 4 hours, other is operated with embodiment one, get pseudo ionone 560.0kg, yield is 80.5%.
Embodiment three
With 1,1,1-trichloroethane 180.0g, vitriol oil 240.0g drops in 1 liter of three mouthfuls of reaction flask, starting agitator makes temperature of reaction reduce to 10 ℃, drip the mixed solution of pseudo ionone 60.0g and 2-hydroxyl-4-octyloxy benzophenone 2.0g this moment, and dropping temperature is no more than 10 ℃, and the control flow velocity added in about 1 hour.Be cooled to 0 ℃ then, reaction is 1 hour under this temperature.Drip 30% aqueous sodium persulfate solution 200.0g in mixed liquid, dropping temperature should not surpass 10 ℃, standing demix, and water layer extracts with 3 * 100ml, 1 washing.Merge oil reservoir, underpressure distillation is collected 98-100 ℃/133Pa of cut and is got product 52.2g, yield 87.0%, and ultraviolet spectrophotometer and gas Chromatographic Determination are alpha, beta-lonone content 〉=97.0%, alpha-position content trace.
Embodiment four
900 liters of methylene dichloride, vitriol oil 900kg is in reactor, stirring is cooled to-5 ℃, drip pseudo ionone 300kg and 2-hydroxyl-4-methoxy benzophenone 3.0kg mixed solution, dropping temperature is no more than 8 ℃, and the control flow velocity dripped off in 1 hour, restir reaction 30 minutes, all the other operations get product 253.5kg, yield 84.5% with embodiment three.
Ultraviolet spectrophotometer is measured, and β-position content is 97.5%, and alpha-position content is very little, ignores.
Claims (11)
1, a kind of method of synthetic alpha, beta-lonone, be condensed into pseudo ionone by citral and acetone Clasien-Schmidt reaction, pseudo ionone further is cyclized into alpha, beta-lonone, it is characterized in that, the condensation reaction of citral and acetone is carried out in strong base solution, and adding phase-transfer catalyst and condensation inhibitor, the mol ratio of citral and acetone is 1: 1～1: 10 in the reaction, concentration of lye 1～10%, the add-on of phase-transfer catalyst is 1～10% (mol ratio) of citral, the consumption of condensation inhibitor is 0.01～1.0% (mol ratio) of citral, 20～60 ℃ of temperature of reaction, 2～4 hours reaction times, reaction directly is neutralized to PH=7 with acetic acid after finishing, the condensation product pseudo ionone carries out cyclization with 95～98% the vitriol oil as cyclizing agent, the consumption of the vitriol oil is 1～5 times (weight meter) of pseudo ionone, cyclization carries out under-20～20 ℃ low temperature, make solvent with hydrochloric ether, consumption is 3～5 times (weight meters) of pseudo ionone, and the adding transposition prevents agent, add-on is 0.01～1.0% (mol ratio) of pseudo ionone, 1.5～2 hours cyclization time, the thin up reactant made it hydrolysis after reaction finished, the vitriol that adds 0.1～1.0 times of vitriol oil amount simultaneously is as emulsion splitter, and the concentration of vitriol is 10～30%.
2, method according to claim 1 is characterized in that, the mol ratio of citral and acetone is 1: 5～1: 9 in the condensation reaction, and citral adds in the mode that drips, and the dropping time is 0.5～1.5 hour.
3, method according to claim 1 is characterized in that, condensation reaction is carried out in strong base solution, and concentration of lye is 3～8%.
4, method according to claim 1, it is characterized in that, the phase-transfer catalyst of the citral consumption 1～10% that adds in this condensation reaction comprises following material or its mixture: polyoxyethylene glycol (polymerization degree is 200～1000), crown ether, Tetrabutyl amonium bromide, 4-butyl ammonium hydrogen sulfate, cetyl trimethylammonium bromide or triethyl benzyl ammonia chloride.
5, method according to claim 1, it is characterized in that, the condensation inhibitor that uses in this condensation reaction comprises following material or its mixture: 2,6-di-t-butyl-4-hydroxyl meta-cresol, 4,4-thiobis (the 6-tertiary butyl) meta-cresol, three-(3,5-di-t-butyl-4 hydroxy phenyl) isocyanuric acid ester, 1,3-dimethyl-N-phenyl-to benzyl diamines, N-phenyl-N '-sec.-propyl-Ursol D, 6-oxyethyl group-2,2,4-trimethylammonium-1,2-dihyaroquinoline, antioxidant 1076, antioxidant 1010, antioxidant D NP or antioxidant 4010.
6, method according to claim 1 is characterized in that, in this cyclization, the vitriol oil is as cyclizing agent, and consumption is 2.5～4.5 times (weight meters) of pseudo ionone.
7, method according to claim 1 is characterized in that, this cyclization carries out at low temperatures, and temperature is-18～10 ℃.
8, method according to claim 1 is characterized in that, the used solvent of this cyclization is a proportion greater than 1.0 chlorinated hydrocarbon, comprise orthodichlorobenzene, monochloroethane, 1,2-ethylene dichloride, methylene dichloride, trichloromethane, trifluorochloromethane, 1 or tetracol phenixin.
9, method according to claim 1, it is characterized in that, adopt the benzophenone compound of absorbing wavelength more than 230mm to prevent agent in this cyclization as transposition, comprise 2-hydroxyl-4-methoxy benzophenone, 2-hydroxyl-4-octyloxy benzophenone, 2-hydroxyl-4-oxygen in last of the ten Heavenly stems base benzophenone, 2-hydroxyl-4-dodecyl benzophenone or 2,2 '-dihydroxyl-4,4 '-dimethoxy-benzophenone.
10, method according to claim 1 is characterized in that, pseudo ionone drips under-20～10 ℃ low temperature and carries out in this cyclization, and the dropping time is controlled within an hour, continues reaction 0.5 hour then, and the reaction times is 1.5 hours altogether.
11, method according to claim 1 is characterized in that, the emulsion splitter that this cyclization finishes the back adding comprises Tai-Ace S 150, sodium sulfate or blue vitriol.
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| Application Number | Priority Date | Filing Date | Title |
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| CN94116569A CN1041302C (en) | 1994-10-08 | 1994-10-08 | Synthesis for high purity beta ionone |
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| CN94116569A CN1041302C (en) | 1994-10-08 | 1994-10-08 | Synthesis for high purity beta ionone |
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| CN1041302C true CN1041302C (en) | 1998-12-23 |
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| CN94116569A Expired - Fee Related CN1041302C (en) | 1994-10-08 | 1994-10-08 | Synthesis for high purity beta ionone |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7115553B2 (en) * | 2003-07-10 | 2006-10-03 | International Flavors & Fragrances Inc. | Acetonide fragrance compound |
| CN108329200B (en) * | 2018-03-21 | 2021-03-09 | 万华化学集团股份有限公司 | Method for preparing beta-ionone by using pseudoionone as raw material |
| CN109096073A (en) * | 2018-07-16 | 2018-12-28 | 南京雪郎化工科技有限公司 | A kind of preparation method of pseudo ionone |
| CN109988064B (en) * | 2019-04-28 | 2021-11-19 | 上海应用技术大学 | Selective cyclization method of pseudo ionone |
| CN113979848B (en) * | 2021-10-21 | 2022-11-15 | 上海应用技术大学 | Method for reducing polymerization of beta-ionone in kettle in rectification process |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US455894A (en) * | 1891-07-14 | Method of binding books | ||
| JPS6157530A (en) * | 1984-08-24 | 1986-03-24 | バスフ アクチェン ゲゼルシャフト | Manufacture of ionone |
| CN1065481A (en) * | 1991-03-30 | 1992-10-21 | 厦门大学 | The method of fixed base catalytic synthetic false violet ketone |
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1994
- 1994-10-08 CN CN94116569A patent/CN1041302C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US455894A (en) * | 1891-07-14 | Method of binding books | ||
| JPS6157530A (en) * | 1984-08-24 | 1986-03-24 | バスフ アクチェン ゲゼルシャフト | Manufacture of ionone |
| CN1065481A (en) * | 1991-03-30 | 1992-10-21 | 厦门大学 | The method of fixed base catalytic synthetic false violet ketone |
Non-Patent Citations (1)
| Title |
|---|
| CEREALFOODSWORLD,VOL36 1991.11.11;Carbonell,"Extrationofflavors Withsupercritical Carbon DIOXIDE" * |
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