CN104387240A - Synthetic method of 2-(3,4-dihydroxyphenyl) ethanol - Google Patents
Synthetic method of 2-(3,4-dihydroxyphenyl) ethanol Download PDFInfo
- Publication number
- CN104387240A CN104387240A CN201410663592.5A CN201410663592A CN104387240A CN 104387240 A CN104387240 A CN 104387240A CN 201410663592 A CN201410663592 A CN 201410663592A CN 104387240 A CN104387240 A CN 104387240A
- Authority
- CN
- China
- Prior art keywords
- catechol
- water
- ethanol
- solvent
- glycoloyl
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
-
- 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
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
-
- 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
- C07C45/64—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 introduction of functional groups containing oxygen only in singly bound form
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthetic method of 2-(3,4-dihydroxyphenyl) ethanol. The synthetic method of 2-(3,4-dihydroxyphenyl) ethanol comprises the following steps: preparing 4-chloroacetyl catechol; preparing 4-hydroxyacetyl catechol; and preparing 2-(3,4-dihydroxyphenyl) ethanol by taking pyrocatechol and phosphorus oxychloride as raw materials and Lewis acid (or chloroacetyl chloride) as a catalyst. The synthetic method of 2-(3,4-dihydroxyphenyl) ethanol is low in cost, short in reaction time, simple in after treatment and high in yield and product content.
Description
Technical field
The invention belongs to organic chemistry filed, relate to the chemical synthesis process of natural product 2-(3,4-dihydroxy phenyl) ethanol.
Background technology
2-(3,4-dihydroxy phenyl) ethanol, popular name, Hydroxytyrosol (Hydroxytyrosol).Be a kind of natural polyphenolic compound, it is mainly present in each position of olive with the form of carboxylate Oleuropein, and Oleuropein can obtain the Hydroxytyrosol dissociated after hydrolysis.It is active that research finds that Hydroxytyrosol has the bio-pharmacology being much of value to HUMAN HEALTH, dark in attention that is biological and medical circle in recent years.In scientific research process afterwards, found Hydroxytyrosol also have other a lot of pharmaceutical uses as: Hydroxytyrosol has unusual effect to the prevention of the diseases such as arteriosclerosis, hypertension, heart trouble, Intracerebral hemorrhage and treatment; To person in middle and old age's preventing osteoporosis, bone density is kept to have good effect; There is anti-cancer and cancer-preventing and spectrum antibacterial effect.
The preparation method of 2-(3,4-dihydroxy phenyl) ethanol mainly contains plant extract, chemosynthesis.
Plant extract take Oleuropein as raw material, or enzyme or acid-catalyzed hydrolysis, extracts and obtain from the waste material producing sweet oil.Chemosynthesis mainly contains:
1) with 3,4-dimethoxy phenylethyl alcohol for raw material, demethylation single step reaction obtains product, and demethylating reaction gained yield is lower, and aftertreatment is complicated; 2) with 3,4-dihydroxyl base toluylic acid for raw material.Adopt lithium aluminum hydride as reductive agent in reaction process, severe reaction conditions, be difficult to control, and lithium aluminum hydride cost of material is higher; 3) take tyrosol as raw material.Also use lithium aluminum hydride in this reaction process, be only applicable to the preparation in a small amount in laboratory; 4) take pyrocatechol as raw material.DSM company has applied for two preparation 2-(3,4-dihydroxy phenyl) patent of ethanol route, article 1, route is with pyrocatechol synthesis 3,4-dihydroxyphenyl ethanol acid intermediate, reduction obtains amygdalic acid and carries out reduction again and obtain Hydroxytyrosol, this route needs at substantial solvent, produces a large amount of waste water, and the reaction times is longer; Article 2, route is that pyrocatechol obtains the chloro-1-of 2-(3,4-dihydroxyl) methyl phenyl ketone through Friedel-Crafts reaction, then is hydrolyzed, the obtained Hydroxytyrosol of reduction.Used valuable metal-salt in this method hydrolytic process, long reaction time, aftertreatment is relative complex also, and reduction step then uses the method for high-pressure hydrogenation, and yield and content are not very desirable.
Summary of the invention
In order to solve technical problem existing in background technology, the invention provides the synthetic method of a kind of 2-(3,4-dihydroxy phenyl) ethanol, this synthetic method yield is high, and cost is low, is applicable to suitability for industrialized production.
The concrete technical solution of the present invention is as follows:
A kind of synthetic method of 2-(3,4-dihydroxy phenyl) ethanol, comprises the following steps:
1] preparation of 4-chloracetyl catechol
Pyrocatechol and phosphorus oxychloride are reacted as mixed solvent and catalyzer Lewis acid (or chloroacetyl chloride), underpressure distillation, then adds water and stirs, and is cooled to room temperature, filters, is washed to neutrality, both obtains 4-chloracetyl catechol; The mass ratio 1:3-8:1-3 of described pyrocatechol, phosphorus oxychloride, chloroacetyl chloride;
2] preparation of 4-glycoloyl catechol
Under weakly alkaline system, add the 4-chloracetyl catechol of step 1 gained, be warming up to 80 DEG C-120 DEG C reactions, TLC controls reaction end, then underpressure distillation, extracts to obtain 4-glycoloyl catechol with solvent extraction; Described solvent is toluene, ethyl acetate; Described alkaline system refers to NaHCO
3+ water, NaOH+ water, water+DMF, water+acetonitrile+DMF, water+dioxane;
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
Step 2 gained 4-glycoloyl catechol is joined containing NaBH
4with in the solvent of LiCl, stirring at normal temperature is even, adds the reaction of catalyzer methanol eddy, TLC controls reaction end, then underpressure distillation, is extracted with ethyl acetate to obtain organic phase, namely drying, filtration, concentrating under reduced pressure obtain 2-(3,4-dihydroxy phenyl) ethanol; Described solvent is glycol dimethyl ether or tetrahydrofuran (THF), and the mass ratio of described LiCl, NaBH4,4-glycoloyl catechol is 0.4:1:2.5-3.5; The mass ratio of described methyl alcohol, solvent, 4-glycoloyl catechol is 0.5:3-5:1.
Extract described in above-mentioned steps 2-3 and at least carry out three times.
In above-mentioned steps 2, weakly alkaline system preference is water+DMF, and wherein the mass ratio of water and DMF is 1:1-3.
Advantage of the present invention is as follows:
The synthetic method cost of this 2-(3,4-dihydroxy phenyl) ethanol is low, the reaction times is short, post-processed is simple, yield and content high.
Embodiment
The synthetic method of this 2-(3,4-dihydroxy phenyl) ethanol comprises following synthetic route:
Embodiment 1
1] preparation of 4-chloracetyl catechol
In four mouthfuls of dry reaction flasks, add pyrocatechol 50g, 375g phosphorus oxychloride, 100g chloroacetyl chloride reflux about 5h, and raw material reaction is complete, underpressure distillation solvent to two/mono-, be cooled to 80 DEG C, slowly drip water 100ml, stir, continue the 100ml stirring that adds water, be cooled to room temperature, filter, be washed to neutrality and obtain product 69g.
2] preparation of 4-glycoloyl catechol
In reaction flask, drop into above-mentioned reaction product 4-chloracetyl catechol 20g, DMF55ml, water 45ml, heat up about 110 DEG C of reactions, TLC detects, and 3h has reacted, and decompression and solvent recovery is to half-dried, add water 40ml, 120ml ethyl acetate divides three extractions, merges the recovery of organic solvent under reduced pressure and obtains residue 14.8g, directly carry out the next step.
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
In reaction flask, namely above-mentioned reaction residue adds glycol dimethyl ether 50ml, 7g NaBH4,2.8gLiCl stirring at normal temperature 1h, adds 4-glycoloyl catechol 20g, then slowly drips methyl alcohol 4ml, about 5h drips off, and continues backflow 2h, TLC detection raw material reaction complete, stopped reaction, decompression and solvent recovery is to half-dried, and slowly add water 20ml, extraction into ethyl acetate, merges organic phase, anhydrous sodium sulfate drying, filter, concentrating under reduced pressure obtains product as clear oil and is about 14.2g.
Embodiment 2
1] preparation of 4-chloracetyl catechol
In four mouthfuls of dry reaction flasks, add pyrocatechol 50g, 450g phosphorus oxychloride, 120g chloroacetyl chloride reflux about 5h, and raw material reaction is complete, underpressure distillation solvent to two/mono-, be cooled to 80 DEG C, slowly drip water 100ml, stir, continue the 100ml stirring that adds water, be cooled to room temperature, filter, be washed to neutrality and obtain product 71g.
2] preparation of 4-glycoloyl catechol
In reaction flask, drop into above-mentioned reaction product 4-chloracetyl catechol 15g, DMF45ml, water 40ml, heat up about 105 DEG C of reactions, TLC detects, 2h has reacted, and decompression and solvent recovery is to half-dried, and add water 40ml, 100ml ethyl acetate divides three extractions, merges the recovery of organic solvent under reduced pressure and obtains resistates 11.2g.Directly carry out the next step.
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
In reaction flask, namely above-mentioned reaction residue adds tetrahydrofuran (THF) 60ml, 8g NaBH4,3.2gLiCl stirring at normal temperature 1h, adds 4-glycoloyl catechol 20g, then slowly drips methyl alcohol 4ml, about 4h drips off, and continues backflow 2h, TLC detection raw material reaction complete, stopped reaction, decompression and solvent recovery is to half-dried, and slowly add water 20ml, extraction into ethyl acetate, merges organic phase, anhydrous sodium sulfate drying, filter, concentrating under reduced pressure obtains product as clear oil and is about 13.8g.
Embodiment 3
1] preparation of 4-chloracetyl catechol
In four mouthfuls of dry reaction flasks, add pyrocatechol 50g, 400g phosphorus oxychloride, 150g chloroacetyl chloride reflux about 5h, and raw material reaction is complete, underpressure distillation solvent to two/mono-, be cooled to 80 DEG C, slowly drip water 100ml, stir, continue the 100ml stirring that adds water, be cooled to room temperature, filter, be washed to neutrality and obtain product 73g.
2] preparation of 4-glycoloyl catechol
In reaction flask, drop into above-mentioned reaction product 4-chloracetyl catechol 15g, DMF45ml, water 45ml, heat up about 120 DEG C of reactions, TLC detects, 1.5h has reacted, and decompression and solvent recovery is to half-dried, and add water 40ml, 100ml toluene divides three extractions, merges the recovery of organic solvent under reduced pressure and obtains resistates 10.8g.Directly carry out the next step.
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
In reaction flask, namely above-mentioned reaction residue adds tetrahydrofuran (THF) 80ml, 7.5g NaBH4,2.8gLiCl stirring at normal temperature 1h, adds 4-glycoloyl catechol 20g, then slowly drips methyl alcohol 4ml, about 4h drips off, and continues backflow 3h, TLC detection raw material reaction complete, stopped reaction, decompression and solvent recovery is to half-dried, and slowly add water 20ml, extraction into ethyl acetate, merges organic phase, anhydrous sodium sulfate drying, filter, concentrating under reduced pressure obtains product as clear oil and is about 12.6g.
Embodiment 4
1] preparation of 4-chloracetyl catechol
In four mouthfuls of dry reaction flasks, add pyrocatechol 50g, 300g phosphorus oxychloride, 150g chloroacetyl chloride reflux about 6h, and raw material reaction is complete, underpressure distillation solvent to two/mono-, be cooled to 80 DEG C, slowly drip water 120ml, stir, continue the 100ml stirring that adds water, be cooled to room temperature, filter, be washed to neutrality and obtain product 67g.
2] preparation of 4-glycoloyl catechol
In reaction flask, drop into above-mentioned reaction product 4-chloracetyl catechol 15g, DMF50ml, water 70ml, heat up about 115 DEG C of reactions, TLC detects, 2h has reacted, and decompression and solvent recovery is to half-dried, and add water 40ml, 100ml ethyl acetate divides three extractions, merges the recovery of organic solvent under reduced pressure and obtains resistates 11.5g.Directly carry out the next step.
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
In reaction flask, namely above-mentioned reaction residue adds tetrahydrofuran (THF) 60ml, 8g NaBH4,3.2gLiCl stirring at normal temperature 1h, adds 4-glycoloyl catechol 20g, then slowly drips methyl alcohol 4ml, about 4h drips off, and continues backflow 2h, TLC detection raw material reaction complete, stopped reaction, decompression and solvent recovery is to half-dried, and slowly add water 20ml, 150ml toluene extracts, and merges organic phase, anhydrous sodium sulfate drying, filter, concentrating under reduced pressure obtains product as clear oil and is about 12.9g.
Embodiment 5
1] preparation of 4-chloracetyl catechol
In four mouthfuls of dry reaction flasks, add pyrocatechol 50g, 350g phosphorus oxychloride, 100g chloroacetyl chloride reflux about 6h, and raw material reaction is complete, underpressure distillation solvent to two/mono-, be cooled to 80 DEG C, slowly drip water 100ml, stir, continue the 120ml stirring that adds water, be cooled to room temperature, filter, be washed to neutrality and obtain product 70g.
2] preparation of 4-glycoloyl catechol
In reaction flask, drop into above-mentioned reaction product 4-chloracetyl catechol 15g, DMF45ml, water 65ml, heat up about 90 DEG C of reactions, TLC detects, 2h has reacted, and decompression and solvent recovery is to half-dried, and add water 40ml, 100ml ethyl acetate divides three extractions, merges the recovery of organic solvent under reduced pressure and obtains resistates 10.6g.Directly carry out the next step.
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
In reaction flask, namely above-mentioned reaction residue adds tetrahydrofuran (THF) 60ml, 6.8g NaBH4,2.7gLiCl stirring at normal temperature 1h, adds 4-glycoloyl catechol 206g, then slowly drips methyl alcohol 4ml, about 4h drips off, and continues backflow 2h, TLC detection raw material reaction complete, stopped reaction, decompression and solvent recovery is to half-dried, and slowly add water 20ml, extraction into ethyl acetate, merges organic phase, anhydrous sodium sulfate drying, filter, concentrating under reduced pressure obtains product as clear oil and is about 13.4g.
Claims (3)
1. the synthetic method of 2-(3, a 4-dihydroxy phenyl) ethanol, is characterized in that, comprise the following steps:
1] preparation of 4-chloracetyl catechol
Pyrocatechol and phosphorus oxychloride are reacted as mixed solvent and catalyzer Lewis acid (or chloroacetyl chloride), underpressure distillation, then adds water and stirs, and is cooled to room temperature, filters, is washed to neutrality, both obtains 4-chloracetyl catechol; The mass ratio 1:3-8:1-3 of described pyrocatechol, phosphorus oxychloride, chloroacetyl chloride;
2] preparation of 4-glycoloyl catechol
Under weakly alkaline system, add the 4-chloracetyl catechol of step 1 gained, be warming up to 80 DEG C-120 DEG C reactions, TLC controls reaction end, then underpressure distillation, extracts to obtain 4-glycoloyl catechol with solvent extraction; Described solvent is toluene, ethyl acetate; Described alkaline system refers to NaHCO
3+ water, NaOH+ water, water+DMF, water+acetonitrile+DMF, water+dioxane;
3] preparation of 2-(3,4-dihydroxy phenyl) ethanol
Step 2 gained 4-glycoloyl catechol is joined containing NaBH
4with in the solvent of LiCl, stirring at normal temperature is even, adds the reaction of catalyzer methanol eddy, TLC controls reaction end, then underpressure distillation, is extracted with ethyl acetate to obtain organic phase, namely drying, filtration, concentrating under reduced pressure obtain 2-(3,4-dihydroxy phenyl) ethanol; Described solvent is glycol dimethyl ether or tetrahydrofuran (THF), and the mass ratio of described LiCl, NaBH4,4-glycoloyl catechol is 0.4:1:2.5-3.5; The mass ratio of described methyl alcohol, solvent, 4-glycoloyl catechol is 0.5:3-5:1.
2. the synthetic method of 2-according to claim 1 (3,4-dihydroxy phenyl) ethanol, is characterized in that: the extraction in described step 2-3 at least carries out three times.
3. the synthetic method of 2-according to claim 2 (3,4-dihydroxy phenyl) ethanol, is characterized in that: in described step 2, weakly alkaline system preference is water+DMF, the mass ratio of water and DMF is 1:1-3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410663592.5A CN104387240B (en) | 2014-11-19 | 2014-11-19 | A kind of synthetic method of 2-(3,4-dihydroxy phenyl) ethanol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410663592.5A CN104387240B (en) | 2014-11-19 | 2014-11-19 | A kind of synthetic method of 2-(3,4-dihydroxy phenyl) ethanol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104387240A true CN104387240A (en) | 2015-03-04 |
| CN104387240B CN104387240B (en) | 2016-01-20 |
Family
ID=52605219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410663592.5A Active CN104387240B (en) | 2014-11-19 | 2014-11-19 | A kind of synthetic method of 2-(3,4-dihydroxy phenyl) ethanol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104387240B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101641316A (en) * | 2007-03-07 | 2010-02-03 | 帝斯曼知识产权资产管理有限公司 | Process for the preparation of hydroxytyrosol |
| CN103664536A (en) * | 2012-09-17 | 2014-03-26 | 天津科技大学 | Synthetic method of hydroxytyrosol |
-
2014
- 2014-11-19 CN CN201410663592.5A patent/CN104387240B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101641316A (en) * | 2007-03-07 | 2010-02-03 | 帝斯曼知识产权资产管理有限公司 | Process for the preparation of hydroxytyrosol |
| CN103664536A (en) * | 2012-09-17 | 2014-03-26 | 天津科技大学 | Synthetic method of hydroxytyrosol |
Non-Patent Citations (1)
| Title |
|---|
| 王红亮等: "羟基酪醇的研究进展", 《化工进展》, vol. 29, no. 6, 31 December 2010 (2010-12-31), pages 1133 - 1137 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104387240B (en) | 2016-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106242971B (en) | A kind of chloracetate synthesis in water technology and its new method for preparing 2,4-D ester | |
| CN103435564A (en) | Preparation method of tebuconazole | |
| CN101940947A (en) | Method for preparing polystyrene resin-immobilized Salon-Co (III) catalyst | |
| CN102190628B (en) | Preparation method of 5-fluoro-6-ethyl-4-hydroxypyrimidine intermediate and Voriconazole | |
| CN109776364A (en) | The preparation method of florfenicol midbody V a kind of and Florfenicol preparation method using intermediate V | |
| CN108047012A (en) | A kind of synthetic method of chalcone sanjuanolide | |
| CN101195575B (en) | process for producing (E)-3-dimethoxy-4'-acetoxy diphenyl ethylene | |
| CN104387240B (en) | A kind of synthetic method of 2-(3,4-dihydroxy phenyl) ethanol | |
| CN101870682A (en) | Preparation method of 4-methylthiazolaldehyde-5 | |
| CN102180773B (en) | Method for preparing resveratrol | |
| CN105348063A (en) | New method for synthesizing and refining medicinal paeonol | |
| CN105061172A (en) | Synthetic method for 2-hydroxyl-5-(3-methoxyl propyl) benzaldehyde | |
| CN103319356A (en) | One-step green synthesis process of antimalarial raw material benflumetol | |
| CN104341345B (en) | A kind of synthetic method of 2-methoxyl group-6-ketone-5,6,7,8-tetrahydroquinoline | |
| CN100457722C (en) | Method for synthesis of rivastigmine | |
| CN101003530B (en) | Method for preparing perfluoroalkyl group sulfonyl isoflavone of possessing anticarcinogenesis | |
| CN106866384B (en) | Preparation method of hydroxytyrosol | |
| CN107793379A (en) | A kind of Chinese cassia tree acetal diglycidyl ether and preparation method thereof and purposes | |
| CN103772188B (en) | The preparation method of R-(+)-α-Cyclo hexyl mandelic acid | |
| CN106674135A (en) | Uracil synthesizing method | |
| CN108530280A (en) | The method of acid immobilized ionic liquid-catalyzed synthesis raspberry ketone | |
| CN106187791A (en) | The new preparation process of Toremifene Citrate intermediate | |
| CN103804147A (en) | Preparation method of 4-hydroxyphenethyl alcohol | |
| CN106496089B (en) | A method of preparing Oxiracetam | |
| CN103922943A (en) | Method for preparing fingolimod hydrochloride |
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 | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 710075 Xi'an high tech Zone, Shaanxi hi tech Road, No. 25 Maple Leaf Garden District, block C, No. 157 Patentee after: SHAANXI JIAHE PHYTOCHEM CO., LTD. Address before: 710075 Xi'an high tech Zone, Shaanxi hi tech Road, No. 25 Maple Leaf Garden District, block C, No. 157 Patentee before: Shanxi Jiahe Plant Chemical Co., Ltd. |