CN103232328B - Method for preparing p-hydroxyphenyl ethanol - Google Patents
Method for preparing p-hydroxyphenyl ethanol Download PDFInfo
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- CN103232328B CN103232328B CN201310183569.1A CN201310183569A CN103232328B CN 103232328 B CN103232328 B CN 103232328B CN 201310183569 A CN201310183569 A CN 201310183569A CN 103232328 B CN103232328 B CN 103232328B
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- hydroxyphenylethanol
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- hydroxyphenylaceticacid
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Abstract
The invention provides a method for preparing p-hydroxyphenyl ethanol, relating to a preparation method of a compound. The method for preparing the p-hydroxyphenyl ethanol, provided by the invention, has the advantages of simplicity in operation, environmental friendliness, high yield, reusable catalyst and applicability to industrial production. The method comprises the steps of: putting p-hydroxyphenyl acetate serving as a raw material, a copper-based catalyst serving as a hydrogenation catalyst, and a reaction solvent in a reaction vessel, replacing air in the reaction vessel with nitrogen gas and hydrogen gas respectively, and then, reacting; and carrying out depressurized spin drying on a solution after reacting, recovering the reaction solvent so as to obtain white solids, recrystallizing by using chloroform so as to obtain colorless needle-like crystals, filtering out precipitated crystals, washing filter cakes with water, and then, carrying out vacuum drying, thereby obtaining the p-hydroxyphenyl ethanol. The copper-based catalyst is used, so that the catalyst is little in consumption and can be reused; used solvents can be all recovered, so that the environmental protection and cost reduction are benefited; and the yield of the p-hydroxyphenyl ethanol is high and can reach over 80% at highest.
Description
Technical field
The present invention relates to a kind of preparation method of compound, especially a kind of by the method for p-hydroxyphenylaceticacid ester catalysis Hydrogenation for p-hydroxyphenylethanol.
Background technology
P-hydroxyphenylethanol (has another name called β-p-hydroxyphenylethanol, tyrosol) be a kind of important medicine and fragrance intermediates, many useful medicines can be synthesized, as being used for the treatment of the betaxolol of open-angle mass color eye, being used for the treatment of the rhodioloside of cough due to lung-heat and seasonal febrile diseases and being used for the treatment of the metoprolol etc. of hypertension and myocardial infarction.
Synthesis p-hydroxyphenylethanol method comprise fermentation method, 4 replace phenol derivatives be Material synthesis method, with aldehyde be the synthesis method of intermediate, phenylethylamine synthesis method, phenylethyl alcohol synthesis method, with 4 replace oil of mirbane for Material synthesis method and ester reduction method etc.It is raw material with 4-hydroxyphenylacetic acid ethyl ether that method disclosed in Chinese patent CN101225023A proposes, and obtain corresponding alcohol with Lithium Aluminium Hydride or sodium borohydride low-temperature reduction ester, yield is 72%, but there is the more expensive and shortcoming that consumption is large of reductive agent.Method disclosed in Chinese patent CN100432035C for raw material, prepares p-hydroxyphenylethanol through over-churning, haloalkylation and hydrolysis three technological processs with phenol and diacetyl oxide, although raw material sources are extensive, and complex process.Method disclosed in Chinese patent CN101066911A is with the mixing of palkoxy benzene ethanol, organic solvent, mineral acid and water, and at 30 ~ 60 DEG C, hydrolysis reaction prepares p-hydroxyphenylethanol, and yield is 72%.In European patent EP 0449603 and U.S. US5003115, adopt 4-acetoxy-styrene to be raw material, adopt peroxycarboxylic acid oxidation, hydrogen reducing reaction, saponification reaction, finally obtained p-hydroxyphenylethanol.But no matter with palkoxy benzene ethanol or 4-acetoxy-styrene for raw material, all because raw material difficulty is asked, be difficult to realize industrialized production.In Japanese Patent JP200327610, phenol and oxyethane is adopted to be raw material, with metallic compound or Lewis acid for catalyzer, one-step synthesis p-hydroxyphenylethanol at low temperatures, but catalyzer be the organometallic compound such as butyllithium, butyl potassium, because air very easily spontaneous combustion met by these catalyzer, working conditions is harshness and dangerous property comparatively.In sum, although the method for synthesis p-hydroxyphenylethanol has a lot, commonly have that cost is high, reaction conditions requirement is high, use dangerous greatly, complex process and the deficiency such as yield is low, be difficult to realize industrialization.
Summary of the invention
The object of the present invention is to provide simple to operate, environmental friendliness, yield are high and catalyzer is reusable, be applicable to a kind of preparation method of p-hydroxyphenylethanol of suitability for industrialized production.
The present invention includes following steps:
1) with p-hydroxyphenylaceticacid ester for raw material, take copper-based catalysts as hydrogenation catalyst, raw material, hydrogenation catalyst and reaction solvent thrown in reaction vessel, react after air with in nitrogen, hydrogen exchange reaction vessel respectively;
2) reacted solution decompression is spin-dried for, reclaims reaction solvent, obtain white solid, carry out recrystallization with chloroform, obtain colourless acicular crystal, leach the crystal of precipitation, carry out vacuum-drying after filter cake washing, obtain p-hydroxyphenylethanol.
In step 1), the mass ratio of described raw material, hydrogenation catalyst and reaction solvent can be raw material: hydrogenation catalyst: reaction solvent=1: (0.05 ~ 1): (0.02 ~ 0.5); The temperature of described reaction can be 150 ~ 270 DEG C, and the pressure of reaction can be 5 ~ 10MPa, and the time of reaction can be 2 ~ 24h; Described p-hydroxyphenylaceticacid ester can be selected from the one in p-hydroxyphenylaceticacid methyl esters, 4-hydroxyphenylacetic acid ethyl ether etc., preferred p-hydroxyphenylaceticacid methyl esters; Described copper-based catalysts can be selected from CuO-ZnO-Al
2o
3, CuO-Cr
2o
3, CuO-ZrO
2, CuO-MnO
2, CuO-SiO
2deng the one in catalyzer, in catalyzer, CuO content can be 10% ~ 90% by mass; Described reaction solvent can be selected from the one in the haloalkane, acetone, tetrahydrofuran (THF) etc. of the alcohol of C1 ~ C4, C1 ~ C4, and the alcohol of described C1 ~ C4 can be selected from the one in methyl alcohol, ethanol, Virahol etc., particular methanol; The haloalkane of described C1 ~ C4 can be selected from the one in ethylene dichloride, chloroform, tetracol phenixin etc.
The present invention compares with existing technology has following distinguishing feature: the present invention uses copper-based catalysts, and catalyst levels is few and reusable; Use solvent all can recycle, be conducive to environment protection and reduce costs; P-hydroxyphenylethanol yield is high, reaches as high as more than 80%.
Embodiment
The present invention is described further by the following examples.
Embodiment 1
With in the 100ml autoclave of whipping appts, 20.0g p-hydroxyphenylaceticacid methyl esters is dissolved in 40.0ml methyl alcohol, adds the CuO-ZnO-Al after 2g reduction
2o
3catalyzer, passes into nitrogen and to get rid of in autoclave air three times, then pass into hydrogen exchange three times.Be 5.0MPa in reaction pressure, temperature of reaction is keep 24h under 220 DEG C of conditions.Collect the rear solution of reaction, adopt high performance liquid chromatography to detect product, chromatographic column is C18 post, UV-detector, ultraviolet detection wavelength 277nm, column temperature 25 DEG C.P-hydroxyphenylethanol yield is 50.2%.
Purification of products: be spin-dried for by reacted solution decompression, recycling design methyl alcohol, obtains white solid.Carry out recrystallization with chloroform, obtain colourless acicular crystal.Leach the crystal of precipitation, carry out vacuum-drying after filter cake washing and obtain p-hydroxyphenylethanol.
Embodiment 2
The preparation method of p-hydroxyphenylethanol, detection method and method of purification with embodiment 1, but during reaction in autoclave reaction pressure be 7.5MPa, the reaction times is 8h.Other condition is constant, and p-hydroxyphenylethanol yield is 82.4%.
Embodiment 3
The preparation method of p-hydroxyphenylethanol, detection method and method of purification with embodiment 1, but during reaction in autoclave reaction pressure be 10.0MPa, but the reaction times is 2h.Other condition is constant, and p-hydroxyphenylethanol yield is 40.7%.
Embodiment 4
The preparation method of p-hydroxyphenylethanol, detection method and method of purification with embodiment 2, but this reaction response time be 16h, other condition is constant, and p-hydroxyphenylethanol yield is 88.6%.
Embodiment 5
The preparation method of p-hydroxyphenylethanol, detection method and method of purification with embodiment 2, but this reaction response time be 24h, other condition is constant, and p-hydroxyphenylethanol yield is 92.2%.
Embodiment 6
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but autoclave interior reaction temperature is 150 DEG C, and the reaction times is 24h, and other condition is constant, and p-hydroxyphenylethanol yield is 60.2%.
Embodiment 7
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but autoclave interior reaction temperature is 270 DEG C, and the reaction times is 1h, and other condition is constant, and p-hydroxyphenylethanol yield is 55.5%.
Embodiment 8
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but catalyzer adopts the CuO-Cr after reduction
2o
3catalyzer, raw material choose 4-hydroxyphenylacetic acid ethyl ether, ethanol selected by solvent.P-hydroxyphenylethanol yield is 70.8%.
Embodiment 9
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but catalyzer adopts the CuO-MnO after reduction
2catalyzer, tetracol phenixin selected by solvent.P-hydroxyphenylethanol yield is 72.8%.
Embodiment 10
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but catalyzer adopts the CuO-ZrO after reduction
2catalyzer, acetone selected by solvent.P-hydroxyphenylethanol yield is 57.7%.
Embodiment 11
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2, but catalyzer adopts the CuO-SiO after reduction
2catalyzer, tetrahydrofuran (THF) selected by solvent.P-hydroxyphenylethanol yield is 68.7%.
Embodiment 12
The preparation method of p-hydroxyphenylethanol, detection method and method of purification are with embodiment 2.Wherein, after reaction terminates, reacted liquid is taken out, rejoin solvent methanol and the p-hydroxyphenylaceticacid methyl esters of same dosage.React under the same conditions, result is shown in table 1.
Table 1. reactive behavior and stability test
| Catalyst reaction number of times | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| P-hydroxyphenylethanol yield/% | 82.4 | 83.1 | 82.5 | 82.1 | 82.3 | 82.4 | 82.2 |
Can see from table 1, adopt and prepare p-hydroxyphenylethanol in this way that there is higher reactive behavior and stability.
Claims (5)
1. a preparation method for p-hydroxyphenylethanol, is characterized in that comprising the following steps:
1) with p-hydroxyphenylaceticacid ester for raw material, take copper-based catalysts as hydrogenation catalyst, raw material, hydrogenation catalyst and reaction solvent thrown in reaction vessel, react after air with in nitrogen, hydrogen exchange reaction vessel respectively; The temperature of described reaction is 220 DEG C, and the pressure of reaction is 7.5MPa, and the time of reaction is 8 ~ 24h; Described copper-based catalysts is CuO-ZnO-Al
2o
3, in catalyzer, CuO content is 10% ~ 90% by mass; The mass ratio of described raw material, hydrogenation catalyst and reaction solvent is raw material: hydrogenation catalyst: reaction solvent=1: (0.05 ~ 1): (0.02 ~ 0.5); Described p-hydroxyphenylaceticacid ester is selected from the one in p-hydroxyphenylaceticacid methyl esters, 4-hydroxyphenylacetic acid ethyl ether; Described reaction solvent is selected from the one in the alcohol of C1 ~ C4, the haloalkane of C1 ~ C4, acetone, tetrahydrofuran (THF);
2) reacted solution decompression is spin-dried for, reclaims reaction solvent, obtain white solid, carry out recrystallization with chloroform, obtain colourless acicular crystal, leach the crystal of precipitation, carry out vacuum-drying after filter cake washing, obtain p-hydroxyphenylethanol.
2. the preparation method of a kind of p-hydroxyphenylethanol as claimed in claim 1, is characterized in that described p-hydroxyphenylaceticacid ester is selected from p-hydroxyphenylaceticacid methyl esters.
3. the preparation method of a kind of p-hydroxyphenylethanol as claimed in claim 1, is characterized in that the alcohol of described C1 ~ C4 is selected from the one in methyl alcohol, ethanol, Virahol.
4. the preparation method of a kind of p-hydroxyphenylethanol as claimed in claim 3, is characterized in that the alcohol of described C1 ~ C4 is selected from methyl alcohol.
5. the preparation method of a kind of p-hydroxyphenylethanol as claimed in claim 1, is characterized in that the haloalkane of described C1 ~ C4 is selected from the one in ethylene dichloride, chloroform, tetracol phenixin.
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| CN105435798B (en) * | 2014-08-27 | 2018-10-23 | 中国石油化工股份有限公司 | Carboxylate hydrogenation copper base catalyst |
| CN104370706A (en) * | 2014-11-24 | 2015-02-25 | 苏州乔纳森新材料科技有限公司 | Preparation method of p-hydroxyphenylethyl alcohol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19711404A1 (en) * | 1997-03-19 | 1998-09-24 | Hoechst Ag | Process for the preparation of aromatic alcohols |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19711404A1 (en) * | 1997-03-19 | 1998-09-24 | Hoechst Ag | Process for the preparation of aromatic alcohols |
Non-Patent Citations (1)
| Title |
|---|
| 对羟基苯乙醇的合成;缪震元等;《合成化学》;20021230;第10卷(第06期);481-484 * |
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