CN100430360C - Method for improving synthesis of coenzyme Q10 - Google Patents
Method for improving synthesis of coenzyme Q10 Download PDFInfo
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- CN100430360C CN100430360C CNB2005100107870A CN200510010787A CN100430360C CN 100430360 C CN100430360 C CN 100430360C CN B2005100107870 A CNB2005100107870 A CN B2005100107870A CN 200510010787 A CN200510010787 A CN 200510010787A CN 100430360 C CN100430360 C CN 100430360C
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Abstract
The present invention discloses an improved method for synthesizing coenzymes Q10, which comprises: solanesol as raw material reacts with phosphorus trichloride to obtain a compound (I) nonylisoprenyl chloride and reacts with ethyl acetoacetate to obtain a compound (II) nonylisoprenyl acetone; the compound (II) reacts with chloroethylene Grignard reagents to obtain a compound (III) isodecylisopentenyl alcohol; under the function of composite catalysts, the compound (III) reacts with 2, 3-dimethoxy-5-methyl-1, 4-benzenediol to obtain a compound (IV) 2-(decyliso pentenyl)-3-methyl-5, 6-dimethoxy-1-4-benzenediol which is oxidized by the composite catalysts to obtain high-yield coenzymes Q10. The improved method has the advantages of simple and direct steps, high yield and realization of commercial process.
Description
Technical field:
The present invention relates to a kind of ubiquinone
10Synthetic is improved one's methods.
Background technology:
Ubiquinone
10(can abbreviate Co Q as
10If, when comprising homologue, then abbreviating Co Q as, the IUPAC-IUB-CBN name is called Ubiquinone-10, nomenclature of drug is Ubibecarenone), be to obtain at first by separating in the myocardial mitochondria of ox.Being present in the mitochondrial inner membrance of many senior animals and plants based on the mankind, is the neccessary composition of forming respiratory chain.The people in the time of 20 years old, the body coenzyme Q
10Reach maximum, reduced gradually later in 20 years old.Need ubiquinone of fine quality, inexpensive, the energy suitability for industrialized production in the market
10Product.
Summary of the invention:
The objective of the invention is to invent a kind of is starting raw material with eggplant Buddhist nun alcohol, obtain compound (I) prenyl in ninth of the ten Heavenly Stems chlorine with the phosphorus trichloride reaction, obtain compound (II) isoprene in ninth of the ten Heavenly Stems benzylacetone with the methyl aceto acetate reaction again, II and the reaction of vinylchlorid Grignard reagent obtain compound III: isodecyl isopentene group alcohol (III) and 2,3-dimethoxy-5-methyl isophthalic acid, the 4-dihydroxy-benzene under the effect of composite catalyst, take place to pay a gram react compound IV: 2-(prenyl in the last of the ten Heavenly stems)-3-methyl-5,6-dimethoxy 1-4-dihydroxy-benzene, IV gets high yield ubiquinone in the combination catalyst oxidation
10, can realize suitability for industrialized production.
The present invention seeks to realize like this: a kind of ubiquinone
10Synthetic is improved one's methods, it is characterized in that with eggplant Buddhist nun alcohol be raw material, in normal hexane and DMF liquid, obtain compound (I) prenyl in ninth of the ten Heavenly Stems chlorine with the phosphorus trichloride reaction, compound (I) obtains compound (II) isoprene in ninth of the ten Heavenly Stems benzylacetone with the methyl aceto acetate reaction again, compound (II) obtains compound (III) isodecyl isopentene group alcohol with the reaction of vinylchlorid Grignard reagent, compound (III) and 2,3-dimethoxy-5-methyl isophthalic acid, the 4-dihydroxy-benzene under the effect of composite catalyst, react compound (IV) 2-(prenyl in the last of the ten Heavenly stems)-3-methyl-5,6-dimethoxy 1-4-dihydroxy-benzene, compound (IV) gets high yield ubiquinone in the combination catalyst oxidation
10
The chemical name of Compound I～IV and structural formula:
Compound I: the ninth of the ten Heavenly Stems prenyl chlorine
Compound I I: the ninth of the ten Heavenly Stems isoprene benzylacetone
Compound III: isodecyl isopentene group alcohol
Compound IV: 2. (prenyl in the last of the ten Heavenly stems)-3-methyl-5,6-dimethoxy-1,4 diphenol
Catalyzed reaction composite catalyst SA05+Lewi s acid (AlCl
3, ZnCL
2, BF
3); Catalytic oxidant: FERRIC CHLORIDE ANHYDROUS+SB05; In magnesium chips and anhydrous tetrahydro furan mixing solutions, heating feeds vinyl chloride production vinylchlorid Grignard reagent down.
Synthesizing coenzyme Q of the present invention
10Improve one's methods that to have step simple and direct, the advantage that yield is high can realize suitability for industrialized production.
Embodiment:
Compound is assisted plum Q
10Preparation condition:
1, the preparation of Compound I:
Reaction mass optimum mole ratio: eggplant Buddhist nun alcohol: phosphorus trichloride=1: 1.2; Eggplant Buddhist nun alcohol: normal hexane: DMF mass ratio=1: 3: 1.5; Temperature of reaction is a room temperature; Reaction solvent normal hexane, ether; Reaction times is 1-1.2h; Reaction yield: 100%.
2, the preparation of Compound I I:
Reaction mass optimum mole ratio: Compound I: methyl aceto acetate: sodium=1: 1.5: 1.5; Reaction solvent: dehydrated alcohol; Temperature of reaction is a room temperature; Reaction times is 6h-8h; Reaction yield: 92%.
3, the preparation of compound III:
Reaction mass optimum mole ratio: Compound I I: vinylchlorid Grignard reagent=1: 1.2; Reaction solvent is anhydrous tetrahydro furan or ether; Temperature of reaction is a room temperature; Reaction yield reaches 91.95%
4, the preparation of composite catalyst: commercially available SA05 (giving birth to biotechnology Advisory Services from the Kunming favour buys), 5g+2mgLewis acid (AlCl
3, ZnCL
2, BF
3)+10ml Nitromethane 99Min..
5, compound IV and ubiquinone
10Preparation:
The preparation of compound IV:
The preparation of assembly catalyze oxygenant: SB05 (giving birth to biotechnology Advisory Services from the Kunming favour buys)+iron trichloride+Virahol; Reaction mass optimum quality ratio: compound (III): FERRIC CHLORIDE ANHYDROUS+sherwood oil+SB05=1: 0.8: 0.2; Reaction solvent selects normal hexane-Virahol, and temperature of reaction is a room temperature; About 1h of reaction times; Reaction yield (with respect to compound III) is 55%.
Embodiment 1
Get 32.4g (0.05mol) eggplant Buddhist nun alcohol and be dissolved in the 100mL normal hexane, splash into the 30mL hexane solution that is dissolved with 6.4g (0.06mol) phosphorus trichloride under 50ml N, N dimethyl formamide (DMF) room temperature, 15min drips off, stir 45min then, add the 200mL saturated aqueous common salt, tell the upper strata, anhydrous sodium sulfate drying, evaporate to dryness gets compound (I) 33.35g, yield 100%.
Get 9.75g (0.075mol) methyl aceto acetate and dissolve in the 50mL dehydrated alcohol, add sodium Metal 99.5 1.72g (0.075mol), treat sodium Metal 99.5 molten intact after, above-mentioned compound (I) 33.35g (0.05mol) that gets of impouring, stir 2h, add the sodium hydroxide solution of 200mL5%, stir 4h, petroleum ether extraction, drying, evaporate to dryness, chromatography, vacuum-drying get compound (II) 30.7g, yield 92%.
Compound (II) 30.7g (0.046mol) of gained is added in the anhydrous tetrahydrofuran solution of vinyl-chloride-containing Grignard reagent 4.3g (0.05mol), stir 1h, leave standstill petroleum ether extraction, anhydrous sodium sulfate drying, evaporate to dryness, column chromatography get compound (III) 28.23g, yield 91.95%.
Embodiment 2
The preparation SA05 of composite catalyst, 5g+2mgLewis acid (AlCl
3, ZnCL
2, BF
3)+10ml Nitromethane 99Min..
Get compound (III) 10g (0.014mol) and be dissolved in the 15mL normal hexane, 2,3-dimethoxy-5-methyl isophthalic acid, 4-dihydroxy-benzene 5g (0.027mol) is dissolved in the 10ml Nitromethane 99Min., and the two mixing adds composite catalyst 11g, 45 ℃, stir 0.5h, tell the upper strata, add the 3g SB05 that contains the 8g FERRIC CHLORIDE ANHYDROUS, 20mL Virahol petroleum ether solution stirs 1h, tells the upper strata, lower floor's petroleum ether extraction, merging, drying, evaporate to dryness, column chromatography, acetone recrystallization get ubiquinone
10Heavy 7g, MP:50-51 ℃.
Claims (2)
1, a kind of ubiquinone
10Synthetic is improved one's methods, it is characterized in that with eggplant Buddhist nun alcohol be raw material, at normal hexane and N, obtain compound (I) prenyl in ninth of the ten Heavenly Stems chlorine with the phosphorus trichloride reaction in the N dimethyl formamide liquid, compound (I) obtains compound (II) isoprene in ninth of the ten Heavenly Stems benzylacetone with the methyl aceto acetate reaction again, compound (II) obtains compound (III) isodecyl isopentene group alcohol with the reaction of vinylchlorid Grignard reagent, compound (III) and 2,3-dimethoxy-5-methyl isophthalic acid, the 4-dihydroxy-benzene under the effect of composite catalyst, react compound (IV) 2-(prenyl in the last of the ten Heavenly stems)-3-first 5,6-dimethoxy 1-4-dihydroxy-benzene, compound (IV) get high yield ubiquinone under the effect of assembly catalyze oxygenant
10, the chemical name of Compound I～IV and structural formula:
Compound I: the ninth of the ten Heavenly Stems prenyl chlorine
Compound I I: the ninth of the ten Heavenly Stems isoprene benzylacetone
Compound III: isodecyl isopentene group alcohol
Compound IV: 2. (prenyl in the last of the ten Heavenly stems)-3-methyl-5,6-dimethoxy-1,4-dihydroxy-benzene
Described catalyzed reaction composite catalyst SA05+Lewis acid AlCl
3, ZnCl
2, BF
3,
Described catalytic oxidant: FERRIC CHLORIDE ANHYDROUS+SB05.
2, a kind of ubiquinone according to claim 1
10Synthetic is improved one's methods, and it is characterized in that in magnesium chips and anhydrous tetrahydro furan mixing solutions, and heating feeds vinyl chloride production vinylchlorid Grignard reagent down.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100107870A CN100430360C (en) | 2005-04-30 | 2005-04-30 | Method for improving synthesis of coenzyme Q10 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100107870A CN100430360C (en) | 2005-04-30 | 2005-04-30 | Method for improving synthesis of coenzyme Q10 |
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| Publication Number | Publication Date |
|---|---|
| CN1696095A CN1696095A (en) | 2005-11-16 |
| CN100430360C true CN100430360C (en) | 2008-11-05 |
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ID=35349009
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100107870A Expired - Fee Related CN100430360C (en) | 2005-04-30 | 2005-04-30 | Method for improving synthesis of coenzyme Q10 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106316777B (en) * | 2016-08-17 | 2019-01-08 | 巨化集团技术中心 | A kind of preparation method of 2,3,3,3- tetrafluoropropene |
| CN112147256A (en) * | 2020-09-25 | 2020-12-29 | 上海普康药业有限公司 | Coenzyme Q determination based on LC-MS10Method for preparing solanesol chloride in capsule |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6686485B2 (en) * | 2001-04-19 | 2004-02-03 | Daniel David West | Synthesis of coenzyme Q10, ubiquinone |
-
2005
- 2005-04-30 CN CNB2005100107870A patent/CN100430360C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6686485B2 (en) * | 2001-04-19 | 2004-02-03 | Daniel David West | Synthesis of coenzyme Q10, ubiquinone |
Non-Patent Citations (2)
| Title |
|---|
| a novel solvent effect in the practical synthesis ofubiquinone-10. Hirozumi ETO.CHEMISTRY LETTERS. 1988 |
| a novel solvent effect in the practical synthesis ofubiquinone-10. Hirozumi ETO.CHEMISTRY LETTERS. 1988 * |
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|---|---|
| CN1696095A (en) | 2005-11-16 |
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