CN1803754A - High-content 9,11 conjugated linoleic acid composition and preparation method thereof - Google Patents
High-content 9,11 conjugated linoleic acid composition and preparation method thereof Download PDFInfo
- Publication number
- CN1803754A CN1803754A CN 200610042189 CN200610042189A CN1803754A CN 1803754 A CN1803754 A CN 1803754A CN 200610042189 CN200610042189 CN 200610042189 CN 200610042189 A CN200610042189 A CN 200610042189A CN 1803754 A CN1803754 A CN 1803754A
- Authority
- CN
- China
- Prior art keywords
- content
- conjugated linolic
- preparation
- viscotrol
- composition
- 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.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The disclosed preparation method for the compositions contained 95-99% 9, 11-conjugate linoleic acid, 1-5% other fatty acids and no 10, 12CLA comprises: selecting castor oil as material; sulfonylating directly the hydroxyl of ricinoleic acid connected with triglyceride without dissociating the ricinoleic acid from triglyceride; with desacylation catalyst instead of costly DBU, taking desacylation hydrolysis and acidifying with HCl to prepare the final product. This invention simplifies process and reduces cost.
Description
Technical field
The present invention relates to the improvement of conjugated linolic acid technology, specifically is a kind of composition and method of making the same of high-content 9,11 conjugated linolic acids, and it belongs to pharmaceutical chemistry technical field.
Background technology
In the prior art, useful Viscotrol C synthesis of conjugated linoleic acid (Body et al, 1965; Berdeaux et al, 1997).It is with methyl ricinoleate (12-hydroxyl-cis Octadec-9-enoic Acid) mass production c9, t11 methyl linoleate.Viscotrol C is in methylene dichloride and methanol solution, and esterification takes place down for sodium and reflux conditions, through the separation and purification methyl ricinoleate.With hexane and methyl alcohol is solvent, separates methyl ricinoleate by the troposphere analysis method, and the purity of the methyl ricinoleate that obtains behind the purifying is 98.5%.With this methyl ricinoleate and Methanesulfonyl chloride reaction, generate 12-first sulphur oxygen based oleic acid methyl esters.The toluene solution of 12-methylsulfonyl oxygen Witconol 2301 is back flow reaction under the catalysis of alkali DBU (1,8-diazabicyclo [5.4.0] undecane-7-alkene) or DBN (1,5-diazabicyclo [4.3.0] nonane-5-alkene), and the product that obtains mainly is c9, the t11CLA methyl esters.
Chinese patent CN01141302.6 relates to a kind of method that is prepared conjugated linolic acid by synourin oil; this method is to be raw material with synourin oil; isomerization is induced in employing; hydrolysis separates with multistep makes; concrete steps are pressed example and are carried out: induce isomerization reaction a; propylene glycol or ethylene glycol or methyl-sulphoxide or nitrogen dimethylformamide 200-600 gram and highly basic potassium hydroxide or the mixing of sodium hydroxide 100-300 gram are placed reaction vessel; under mechanical stirring, blast nitrogen protection and be heated to 150-170 ℃; churning time 15-30 minute; 200-400 being restrained synourin oil adds again; be warming up to 175-190 ℃; drop to room temperature in nitrogen protection, it is standby to obtain alternative.B, a part of alternative charged into nitrogen under airtight after in 60 times irradiations of cobalt, absorption dose 1-40 kilogray (kGy).C, place microwave oven to heat another part alternative, time 0.5-8 minute.Hydrolysis reaction: with b, c gained alternative be hydrolyzed respectively the reaction d, b, c gained alternative are put into reaction vessel respectively, nitrogen protection under mechanical stirring respectively, be heated to 180 ℃ of sustained reactions 2.5 hours, be cooled to room temperature, adding the 180ml concentrated hydrochloric acid stirred 20 minutes, adjust PH=2-4, reduce to room temperature after hydrolysis finishes, leave standstill that branch anhydrates and glycerine, wash 5-6 time then, be washed till PH=6.5-7.5, elder generation's sedimentation divides water, separates organic phase and water with whizzer again, and the organic phase that separation obtains is stand-by, obtain being mainly 9c, 11t; 10t, 12cCLA target product conjugated linolic acid, cla levels 〉=80% wherein, linoleic acid content 〉=15% contains a small amount of other conjugated linoleic acid isomers.
Above-mentioned prior art is produced 9c, and the 11t conjugated linolic acid (be called for short: 9,11 conjugated linolic acids, or 9, the problem that method 11CLA) exists are, complex manufacturing, and product purity is low, the production cost height.
Summary of the invention
Goal of the invention of the present invention is: the drawback that overcomes prior art, at the problem that existing method exists, simplify technology, reduce cost, improve product purity, design a kind of new processing technology routine, realize with the Viscotrol C being raw material, the preparation 9 of adopting new technology, 11CLA, reduce reactions steps, 9,11 CLA content reach at least 95 in the product---and 99%.
The objective of the invention is to realize, developed a kind of composition of high-content 9,11 conjugated linolic acids by following technical scheme.9 of said composition, 11-conjugated linolic acid total content is at least 95---and 99%, other fatty acid content 1---5%; Said composition is a colourless oil liquid.
A kind of preparation method of composition of above-mentioned high-content 9,11 conjugated linolic acids, it carries out as follows:
(1) with the Viscotrol C be raw material, it be dissolved in the solvent that mixes, add an amount of triethylamine, stir and be cooled to 0---5 ℃;
(2) in ice bath, drip methylsulfonyl chloride, carry out the methylsulfonyl reaction, temperature of reaction 0---5 ℃, the stirring reaction time 30---60 minutes;
(3) add an amount of hydrochloric acid in the reaction product that reaction is finished, acid elution twice is used distilled water wash three times again;
(4) the reaction product anhydrous sodium sulfate drying that the washing of (3) step is finished;
(5) dried reaction product of (4) step is filtered with the conventional filtration device, remove anhydrous sodium sulphate;
(6) with the conventional rotatory evaporator of reaction product after the filtration of (5) step, remove and reclaim solvent, make the methylsulfonyl Viscotrol C;
(7) take by weighing the methylsulfonyl Viscotrol C that (6) step makes, add the catalyst based solution of deacylated tRNA and carry out deacylated tRNA base hydrolysis reaction,---reacted 2 under 70 ℃---8 hours 50;
(8) reaction product that the reaction of (7) step is finished is taken out and is placed to room temperature, adds an amount of distilled water, uses an amount of hcl acidifying again, and 9,11 conjugate linoleates are converted into 9,11 conjugated linolic acids;
(9) 9,11 conjugated linolic acids of the conversion that (8) are gone on foot wash with saturated nacl aqueous solution;
(10) with 9, the 11 conjugated linolic acids anhydrous sodium sulfate drying of (9) step flush away hydrochloric acid, remove its moisture, filter with the conventional filtration device again, remove anhydrous sodium sulphate;
(11) (10) step exsiccant conjugated linolic acid is concentrated through three grades of molecule distillation purifyings again, obtaining content is 95---the colourless oil liquid of 99% 9,11 conjugated linolic acids.
The solvent of described (1) step dissolving Viscotrol C is methylene dichloride, chloroform, toluene or dimethylbenzene.
It is that g/ml ratio in Viscotrol C/triethylamine is 1: 1 that described (1) step adds an amount of triethylamine.
The add-on of described (2) ground beetle SULPHURYL CHLORIDE is that the mol/mol ratio in Viscotrol C/methylsulfonyl chloride is 1: 1.05---1.20.
Described (4) or (10) step use anhydrous sodium sulfate drying, wherein the weight ratio of Viscotrol C/anhydrous sodium sulphate is 1: 1.
Described (7) step deacylated tRNA is catalyst based to be sodium hydroxide, potassium hydroxide, sodium ethylate, potassium ethylate, sodium methylate, potassium methylate, sodium propylate, potassium tert.-butoxide or potassium isopropoxide; The catalyst based mol/mol ratio of methylsulfonyl Viscotrol C/deacylated tRNA is 1: 1.10---1.20.
The consumption that described (8) step adds distilled water is 1.10 times of 5 heavy---10 times, the hydrochloric acid consumption of hcl acidifying are 1.05 of an alkali consumption---of Viscotrol C.
Described (9) step washs with saturated nacl aqueous solution, washing 2---and 3 times.
Three grades of molecule distillations in described (11) step, its processing condition: first step vacuum tightness 200---400Pa, temperature 110---120 ℃; Second stage vacuum tightness 120---150Pa, temperature 140---150 ℃; Third stage vacuum tightness 5-10Pa, temperature 120---130 ℃.
Innovation part of the present invention is: the particularly important is high-content 9,11 conjugated linolic acids of the present invention composition its with 9,11CLA is a main component, does not contain 10,12CLA, 9,11 cla levels reach more than 95% in the product.
Owing at first adopt the methylsulfonyl reaction, promptly, directly will be connected the alcoholic extract hydroxyl group sulfonylation of the ricinoleic acid on the triglyceride level, make the ricinoleic acid sulfonylation, needn't earlier ricinoleic acid be dissociated out from triglyceride level, just can make the methylsulfonyl Viscotrol C, save esterification technology, reduce reactions steps;
Owing to adopt deacylated tRNA catalyst based, this methylsulfonyl Viscotrol C of making again through the catalyst based deacylated tRNA base hydrolysis reaction of deacylated tRNA, is used an amount of hcl acidifying again, 9,11 conjugate linoleates that hydrolysis is produced are converted into 9,11 conjugated linolic acids; In this deacylated tRNA base hydrolysis reaction, adopt sodium hydroxide, potassium hydroxide, sodium ethylate; potassium ethylate; sodium methylate, potassium methylate, sodium propylate; potassium tert.-butoxide or potassium isopropoxide are catalyst based as deacylated tRNA; replaced expensive dewatering agent DBU, its cost reduces widely, and is to take off alkylsulfonyl and hydrolysis is carried out simultaneously; make preparation technology simple, be easy to suitability for industrialized production.
Embodiment
Embodiments of the invention are as follows:
Embodiment 1,
Take by weighing 10g Viscotrol C (10.79mmol); add the 30ml chloroform, stir and be cooled to 0 ℃, drip methylsulfonyl chloride (5.7ml); react 45min in the ice bath; add 10ml hydrochloric acid (2N), add the 100ml washed twice, anhydrous sodium sulfate drying; after the filtration; rotary evaporation removes and reclaims solvent, obtains the methylsulfonyl Viscotrol C, 10.7g (9.61mmol).Take by weighing 2g (1.80mmol) methylsulfonyl Viscotrol C, 49.7mgNa (2.16mmol) is dissolved in 20ml methyl alcohol, and 50 ℃, reaction 5h; take out and place room temperature, add 20ml distilled water, hcl acidifying, saturated nacl aqueous solution washing; anhydrous sodium sulfate drying obtains 1.7g 9,11 conjugated linolic acids.Refining through molecular distillation, obtain content and be 95.64% 9,11 conjugated linolic acid colourless oil liquid 1.36g.
Embodiment 2---and 10 see Table 1:
Table 1, the present invention 9,11 conjugated linolic acid preparation methods' main technique condition and result
| 1 | 10 | Chloroform/0/45 | Sodium methylate/2.16 | 5/50 | 95.64 |
| 2 | 50 | Chloroform/5/45 | Sodium methylate/59.4 | 3/50 | 95.06 |
| 3 | 50 | Chloroform/5/45 | Sodium ethylate/59.4 | 4/70 | 96.04 |
| 4 | 50 | Methylene dichloride/0/60 | Sodium hydroxide/59.4 | 5/60 | 97.36 |
| 5 | 50 | Methylene dichloride/0/60 | Sodium propylate/59.4 | 3/50 | 97.15 |
| 6 | 100 | Toluene 2/45 | Potassium hydroxide/129.5 | 2/60 | 95.10 |
| 7 | 100 | Dimethylbenzene 2/45 | Potassium ethylate/129.5 | 8/60 | 96.30 |
| 8 | 100 | Chloroform/5/45 | Potassium methylate/129.5 | 5/50 | 96.72 |
| 9 | 100 | Chloroform/5/45 | Potassium tert.-butoxide/129.5 | 5/50 | 97.20 |
| 10 | 100 | Chloroform/5/45 | Potassium isopropoxide/129.5 | 5/50 | 95.60 |
The content assaying method of 9,11 conjugated linolic acids of the present invention is gas chromatography determination (capillary column AC20, internal diameter 0.25mm * 30m, a chromatographic condition: 195 ℃ of column temperatures, 260 ℃ of detectors, 250 ℃ of vaporizers, splitting ratio 60).
Those of ordinary skill in the art can understand, and in protection scope of the present invention, makes amendment for the foregoing description, and it all is possible adding and replacing, and it does not all exceed protection scope of the present invention.
Claims (10)
1, a kind of composition of high-content 9,11 conjugated linolic acids is characterized in that: 9 of said composition, 11-conjugated linolic acid total content be at least at 95-99%, other fatty acid content 1-5%; Said composition is a colourless oil liquid.
2, a kind of preparation method of composition of 9,11 conjugated linolic acids of high-content according to claim 1, it is characterized in that: described preparation method carries out as follows:
(1) with the Viscotrol C is raw material, it is dissolved in the solvent that mixes, add an amount of triethylamine, stir and be cooled to 0-5 ℃;
(2) in ice bath, drip methylsulfonyl chloride, carry out the methylsulfonyl reaction, temperature of reaction 0-5 ℃, 30-60 minute stirring reaction time;
(3) add an amount of hydrochloric acid in the reaction product that reaction is finished, acid elution twice is used distilled water wash three times again;
(4) the reaction product anhydrous sodium sulfate drying that the washing of (3) step is finished;
(5) dried reaction product of (4) step is filtered with the conventional filtration device, remove anhydrous sodium sulphate;
(6) with the conventional rotatory evaporator of reaction product after the filtration of (5) step, remove and reclaim solvent, make the methylsulfonyl Viscotrol C;
(7) take by weighing the methylsulfonyl Viscotrol C that (6) step makes, add the catalyst based solution of deacylated tRNA and carry out deacylated tRNA base hydrolysis reaction, reacted 2-8 hour down at 50--70 ℃;
(8) reaction product that the reaction of (7) step is finished is taken out and is placed to room temperature, adds an amount of distilled water, uses an amount of hcl acidifying again, and 9,11 conjugate linoleates are converted into 9,11 conjugated linolic acids;
(9) 9,11 conjugated linolic acids of the conversion that (8) are gone on foot wash with saturated nacl aqueous solution;
(10) with 9, the 11 conjugated linolic acids anhydrous sodium sulfate drying of (9) step flush away hydrochloric acid, remove its moisture, filter with the conventional filtration device again, remove anhydrous sodium sulphate;
(11) (10) step exsiccant conjugated linolic acid is concentrated through three grades of molecule distillation purifyings again, obtaining content is the colourless oil liquid of 9,11 conjugated linolic acids of 95-99%.
3, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: the solvent of described (1) step dissolving Viscotrol C is methylene dichloride, chloroform, toluene or dimethylbenzene.
4, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: it is that g/ml ratio in Viscotrol C/triethylamine is 1: 1 that described (1) step adds an amount of triethylamine.
5, according to the preparation of compositions method of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: the add-on of described (2) ground beetle SULPHURYL CHLORIDE is that the mol/mol ratio in Viscotrol C/methylsulfonyl chloride is 1: 1.05-1.20.
6, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: described (4) or (10) step use anhydrous sodium sulfate drying, wherein the weight ratio of Viscotrol C/anhydrous sodium sulphate is 1: 1.
7, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: described (7) step deacylated tRNA is catalyst based to be sodium hydroxide, potassium hydroxide, sodium ethylate, potassium ethylate, sodium methylate, potassium methylate, sodium propylate, potassium tert.-butoxide or potassium isopropoxide; The catalyst based mol/mol ratio of methylsulfonyl Viscotrol C/deacylated tRNA is 1: 1.10-1.20.
8, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: the consumption that described (8) step adds distilled water is the heavy 5-10 of Viscotrol C times, and the hydrochloric acid consumption of hcl acidifying is 1.05--1.10 a times of alkali consumption.
9, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: described (9) step washs 2-3 time with the saturated nacl aqueous solution washing.
10, according to the preparation method of composition of described high-content 9,11 conjugated linolic acids of claim 2, it is characterized in that: three grades of molecule distillations in described (11) step, its processing condition: first step vacuum tightness 200-400Pa, temperature 110-120 ℃; Second stage vacuum tightness 120-150Pa, temperature 140-150 ℃; Third stage vacuum tightness 5-10Pa, temperature 120-130 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100421896A CN100369881C (en) | 2006-01-13 | 2006-01-13 | High-content 9,11 conjugated linoleic acid composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100421896A CN100369881C (en) | 2006-01-13 | 2006-01-13 | High-content 9,11 conjugated linoleic acid composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1803754A true CN1803754A (en) | 2006-07-19 |
| CN100369881C CN100369881C (en) | 2008-02-20 |
Family
ID=36865931
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100421896A Expired - Fee Related CN100369881C (en) | 2006-01-13 | 2006-01-13 | High-content 9,11 conjugated linoleic acid composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100369881C (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3017108B2 (en) * | 1996-10-30 | 2000-03-06 | リノール油脂株式会社 | Method for producing conjugated linoleic acid |
| US6153774A (en) * | 1997-02-18 | 2000-11-28 | Seidel; Michael C. | Silver ion chromatography of high purity conjugated linoleic acid (CLA) |
| US5892074A (en) * | 1997-02-18 | 1999-04-06 | Seidel; Michael C. | Synthesis of conjugated linoleic acid (CLA) |
| US6410763B1 (en) * | 1999-04-01 | 2002-06-25 | Michael C. Seidel | Liquid chromatography of high purity conjugated fatty acid |
| CN1289758A (en) * | 1999-09-27 | 2001-04-04 | 济南建基生物基因有限公司 | Process for preparing conjugated linoleic acid |
| CN1137975C (en) * | 2001-09-25 | 2004-02-11 | 中国科学院新疆理化技术研究所 | Process for preparing conjugated linoleic acid from dewatered castor oil |
| CN1596884A (en) * | 2004-07-22 | 2005-03-23 | 国家海洋局第一海洋研究所 | Composition containing high content conjugated linoleic acid and its preparation method |
-
2006
- 2006-01-13 CN CNB2006100421896A patent/CN100369881C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN100369881C (en) | 2008-02-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104619680B (en) | The production method of polyol ester | |
| Ikawa et al. | Preparation and regioselective Diels–Alder reactions of borylbenzynes: Synthesis of functionalized arylboronates | |
| CN1176094C (en) | Synthesis of trichlorosucrose | |
| CN103897025A (en) | Preparation method of pidotimod | |
| CN100369881C (en) | High-content 9,11 conjugated linoleic acid composition and preparation method thereof | |
| CN111499661A (en) | Preparation method of tin oxide complex diisooctanoate | |
| CN103304623B (en) | Synthetic method of 6[beta],19-epoxy androstane-3,17-dione | |
| WO2015094548A1 (en) | Control of color-body formation in isohexide esterification | |
| CN1131871C (en) | Preparation of steriod esters | |
| CN1827216A (en) | Supported catalyst for preparing chiral secondary alcohol under normal pressure and method for preparing the same | |
| CN106674330A (en) | 34-Dimethyl apratoxin A/E preparation method | |
| CN101613279B (en) | Method for preparing chiral compound of (R)-2-hydroxy-4-phenylbutyrate | |
| CN1566064A (en) | Process for preparing azelaic acid by oleic acid phase transfer catalytic oxidation | |
| CN102030632B (en) | Preparation method of 6,8,11,13-tetra-abietic olefine acid | |
| CN114591173B (en) | Plasticizer based on dicyclopentadiene structure and preparation method thereof | |
| CN111233637A (en) | High-purity triglycerol monolaurate and preparation method and application thereof | |
| CN112239406A (en) | Preparation method of hydroxy ester | |
| CN1724557A (en) | Preparation method of 9 alpha, 11 alpha-epoxy-17 beta-hydroxy-3-oxo-17 alpha-pregn-4-ene-7 alpha, 21-dicarboxylic acid gamma-lactone 7-methyl ester | |
| CN112521278B (en) | Method for preparing carboxylic ester compound | |
| CN1844065A (en) | Selective alkylation reaction of acid anhydride or ester | |
| KR101947243B1 (en) | Method of manufacturing muconate including recovery and recycling of spent catalyst | |
| WO2022134297A1 (en) | Preparation method for carboxylate ester compound | |
| CN117886892A (en) | Preparation method of Fuciclosporin | |
| CN114133421A (en) | Preparation method of beta-mouse cholic acid | |
| CN113233980A (en) | Synthesis method of beta-chloroacid ester and alpha, beta-unsaturated acid ester 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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |