CN103804147A - Preparation method of 4-hydroxyphenethyl alcohol - Google Patents
Preparation method of 4-hydroxyphenethyl alcohol Download PDFInfo
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- CN103804147A CN103804147A CN201210442151.3A CN201210442151A CN103804147A CN 103804147 A CN103804147 A CN 103804147A CN 201210442151 A CN201210442151 A CN 201210442151A CN 103804147 A CN103804147 A CN 103804147A
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- 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
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention relates to a preparation method of 4-hydroxyphenethyl alcohol. The preparation method is characterized in that: p-bromophenol is taken as a raw material, and is subjected to a series of reactions such as hydroxyl protection, Grignard reaction, and protecting group removing so as to obtain 4-hydroxyphenethyl alcohol. Product yield of the preparation method reaches about 90%.
Description
Technical field:
The present invention relates to technical field of organic synthesis, particularly, the present invention relates to a kind of preparation method of p-hydroxyphenylethanol.
Background technology:
Base phenylethyl alcohol is a kind of important medicine and spices intermediate, with it can synthesize multiple useful medicine, as: metoprolol (Metoprolol), is used for the treatment of hypertension, stenocardia, irregular pulse and myocardial infarction, also can be used for hyperthyroidism, migraine; Betaxolol (Betaxolol), treatment hypertension, open angle glaucoma; Hordenine, the effective constituent of Fructus Hordei Germinatus, can help digestion and in, for accumulation of food in the stomach and intes tine due to indigestion, anorexia, the diseases such as the breast swell and pain due to abdominal distension and rich female ablactation or galactostasis.
More about its Study of synthesis method, early stage synthetic method is fermentation method, and fermentation time is long, and productive rate is low; Li Guoqing etc. proposed one take 4-hydroxyphenylacetic acid ethyl ether as raw material in 1996, through benzyloxy, reduction, hydrogenation, obtained p-hydroxyphenylethanol, adopted Lithium Aluminium Hydride to make reductive agent, and every step productive rate can reach 90% left and right; Also have take phenylethylamine as raw material, prepare p-hydroxyphenylethanol through digestion, reduction, diazotization, hydrolysis, but productive rate is very low, only have 45% left and right; Take phenylethyl alcohol as raw material, obtain p-hydroxyphenylethanol through esterification, nitration, reduction, hydrogenation, productive rate can reach 70% left and right.
Summary of the invention:
The invention provides a kind of preparation method of p-hydroxyphenylethanol.
For achieving the above object, the technical solution that the present invention adopts is as follows: a kind of preparation method of p-hydroxyphenylethanol, take p bromophenol as raw material, through series reaction such as hydroxyl protection, grignard reaction, Deprotections, prepares p-hydroxyphenylethanol.
Carbonyl-protection is: p bromophenol, 3-bromopropylene, Anhydrous potassium carbonate react and obtain allyloxy bromobenzene; acetone is solvent; temperature is 55 ℃ of backflows; 158 ℃ ~ 162 ℃ cuts are collected in suction filtration, air distillation, underpressure distillation again (10kPa); obtain the oily colourless transparent liquid of irritant strange smell, p bromophenol, 3-bromopropylene, Anhydrous potassium carbonate (molar percentage)=1:1:1.
Grignard reaction is: magnesium, anhydrous tetrahydro furan and two crystal iodine are added in the four neck round-bottomed flasks with magnetic stirring apparatus, soccer star's prolong (band Calcium Chloride Powder Anhydrous drying tube) and thermometer; under nitrogen protection, drip the solution to alkene phenoxy group bromobenzene and anhydrous tetrahydro furan formation.Control rate of addition, first drip on a small quantity, wait reaction to start to continue again to drip after (the brown of iodine shoals, gentle boil), control 50 ~ 55 ℃ of temperature, time for adding 1h left and right.After dropwising, react 15 minutes, water-bath refluxes half an hour again.Reaction solution is cooled to-10 ℃ with salt ice, drip saturated ammonium chloride solution, suction filtration, stratification, oil phase washs with saturated nacl aqueous solution, and anhydrous chlorides of rase sodium is dry, underpressure distillation after first air distillation, collect 140 ℃ of left and right cuts, obtain pungency greyish-green oily liquids, magnesium: alkene phenoxy group bromobenzene (molar percentage)=10:9.
De-carbonyl-protection is: sodium borohydride, alkene phenoxy group phenylethyl alcohol and anhydrous tetrahydro furan are added to four-hole boiling flask, be cooled to-5 ℃ with salt ice, drip the solution that iodine and anhydrous tetrahydro furan form under nitrogen protection.Control rate of addition and make temperature at-2 ℃ ~ 0 ℃, drip off rear continuation reaction 20 minutes, drip methyl alcohol termination reaction, air distillation, filter, obtain weak yellow liquid (mixture), sodium borohydride, to alkene phenoxy group phenylethyl alcohol: iodine (molar percentage)=18:14:7.
The present invention, take p bromophenol as raw material, through series reaction such as hydroxyl protection, grignard reaction, Deprotections, prepares p-hydroxyphenylethanol.Product yield can reach 90% left and right.
Embodiment:
Below in conjunction with specific embodiment, the invention will be further elaborated, but be not limited to these specific embodiments, and all embodiment are all by above-mentioned operation steps operation.
Embodiment 1, preparation to alkene phenoxy group bromobenzene:
In the 100mL tetra-neck flasks with mechanical stirrer, soccer star's prolong and thermometer, add 7g(0.04mol) p bromophenol, 5.1g(0.04mol) 3-bromopropylene and 30mL acetone, under vigorous stirring, add 5.4g(0.04mol) Anhydrous potassium carbonate.Warming-in-water to 55 ℃ backflow 4h, suction filtration, air distillation obtains acetone 14mL, then 158 ℃ ~ 162 ℃ cuts of underpressure distillation (10kPa) collection, obtains the oily colourless transparent liquid 6.4g of irritant strange smell, productive rate 74.3%.
Embodiment 2, preparation to allyloxy phenylethyl alcohol
Because grignard reaction is very strict to requirement of experiment, before experiment, each reactant and experimental installation are done to suitable processing.
The preparation of A, anhydrous tetrahydro furan (THF)
Whether step I, check superoxide exist
Get THF 1 ~ 2mL, add equal-volume 2%KI starch solution and several dilute hydrochloric acid, if be purple or blueness contains or oxide compound, need carry out second step operation, if be colourless or slightly faint yellow explanation without superoxide, can directly carry out Step II I.
Step II, remove superoxide
In 22mL water, splash into the 1.2mL vitriol oil, then add 1.2g ferrous sulfate, stirring and dissolving.In 250mL separating funnel, first place 100mL tetrahydrofuran (THF), copperas solution is added wherein, stopper concuss (venting) beyond the Great Wall, layering, abandons water, then check has or not superoxide.
Step II I, dry with sodium
In THF, add appropriate sodium, reflux, until do not produce hydrogen, distillation, is pressed into sodium silk and preserves.
B, processing to allyloxy bromobenzene
Dry to more than alkene phenoxy group bromobenzene 24h with Calcium Chloride Powder Anhydrous, underpressure distillation, puts into silica gel drier and preserves.
Being dried of C, magnesium powder
Magnesium powder is packed in beaker, and 80 ℃ are dried 1h, then put into silica gel drier and preserve.
Being dried of D, laboratory apparatus
Test required flask, glass stopper, prolong etc. and all need to be placed on 90 ℃ of baking 2h in baking oven, then put into silica gel drier stand-by.
Making solvent with anhydrous tetrahydro furan prepares alkene phenoxy group phenylethyl alcohol
By 2.4g(0.10mol) magnesium, 20mL anhydrous tetrahydro furan and two crystal iodine add in the 250mL tetra-neck round-bottomed flasks with magnetic stirring apparatus, soccer star's prolong (band Calcium Chloride Powder Anhydrous drying tube) and thermometer; under nitrogen protection, drip 19.2g(0.09mol) solution that alkene phenoxy group bromobenzene and 30mL anhydrous tetrahydro furan are formed.Control rate of addition, first drip 5mL left and right, warming-in-water to 50 ℃, waits reaction to start to continue to drip after (the brown of iodine shoals, gentle boil) again, controls 50 ~ 55 ℃ of temperature, time for adding 1h left and right.After dropwising, react 15 minutes, water-bath refluxes half an hour again.Reaction solution is cooled to-10 ℃ with salt ice, drip 50mL saturated ammonium chloride solution, suction filtration, stratification, 40mL saturated nacl aqueous solution washing three times for oil phase, more than the dry 24h of anhydrous chlorides of rase sodium, underpressure distillation after first air distillation (3kPa), collect 140 ° of C left and right cuts, obtain 9.7g pungency greyish-green oily liquids.
The preparation of embodiment 3, p-hydroxyphenylethanol
By 0.7g(0.018mol) sodium borohydride; 2.5g(0.014mol) alkene phenoxy group phenylethyl alcohol and 20mL anhydrous tetrahydro furan are added to 100mL four-hole boiling flask; be cooled to-5 ℃ with salt ice, under nitrogen protection, drip 1.8g(0.007mol) solution that forms of iodine and 10mL anhydrous tetrahydro furan.Control rate of addition and make temperature at-2 ℃ ~ 0 ℃, within approximately 15 minutes, drip off rear continuation reaction 20 minutes, drip 15mL methyl alcohol termination reaction, air distillation, filters, and obtains weak yellow liquid (mixture).
Claims (1)
1. a preparation method for p-hydroxyphenylethanol, is characterized in that: take p bromophenol as raw material, through hydroxyl protection, grignard reaction, deprotection reaction, prepare p-hydroxyphenylethanol;
Described carbonyl-protection is: p bromophenol, 3-bromopropylene, Anhydrous potassium carbonate react and obtain allyloxy bromobenzene, acetone is solvent, temperature is 55 ℃ of backflows, 158 ℃ ~ 162 ℃ cuts are collected in suction filtration, air distillation, underpressure distillation again (10kPa), obtain the oily colourless transparent liquid of irritant strange smell, p bromophenol, 3-bromopropylene, Anhydrous potassium carbonate (molar percentage)=1:1:1;
Described grignard reaction is: magnesium, anhydrous tetrahydro furan and two crystal iodine are added in the four neck round-bottomed flasks with magnetic stirring apparatus, soccer star's prolong (band Calcium Chloride Powder Anhydrous drying tube) and thermometer; under nitrogen protection, drip the solution to alkene phenoxy group bromobenzene and anhydrous tetrahydro furan formation.Control rate of addition, first drip on a small quantity, wait reaction to start to continue again to drip after (the brown of iodine shoals, gentle boil), control 50 ~ 55 ℃ of temperature, time for adding 1h left and right.After dropwising, react 15 minutes, water-bath refluxes half an hour again.Reaction solution is cooled to-10 ℃ with salt ice, drip saturated ammonium chloride solution, suction filtration, stratification, oil phase washs with saturated nacl aqueous solution, and anhydrous chlorides of rase sodium is dry, underpressure distillation after first air distillation, collect 140 ℃ of left and right cuts, obtain pungency greyish-green oily liquids, magnesium: alkene phenoxy group bromobenzene (molar percentage)=10:9;
Described de-carbonyl-protection is: sodium borohydride, alkene phenoxy group phenylethyl alcohol and anhydrous tetrahydro furan are added to four-hole boiling flask, be cooled to-5 ℃ with salt ice, drip the solution that iodine and anhydrous tetrahydro furan form under nitrogen protection.Control rate of addition and make temperature at-2 ℃ ~ 0 ℃, drip off rear continuation reaction 20 minutes, drip methyl alcohol termination reaction, air distillation, filter, obtain weak yellow liquid (mixture), sodium borohydride, to alkene phenoxy group phenylethyl alcohol: iodine (molar percentage)=18:14:7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201210442151.3A CN103804147A (en) | 2012-11-07 | 2012-11-07 | Preparation method of 4-hydroxyphenethyl alcohol |
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| CN201210442151.3A CN103804147A (en) | 2012-11-07 | 2012-11-07 | Preparation method of 4-hydroxyphenethyl alcohol |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111393264A (en) * | 2020-03-10 | 2020-07-10 | 杭州盛弗泰新材料科技有限公司 | Synthetic method of p-hydroxyphenylethanol |
| CN114790131A (en) * | 2021-01-25 | 2022-07-26 | 孚能科技(赣州)股份有限公司 | Positive electrode lithium supplement additive, positive electrode plate, preparation method of positive electrode plate and lithium ion battery |
-
2012
- 2012-11-07 CN CN201210442151.3A patent/CN103804147A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111393264A (en) * | 2020-03-10 | 2020-07-10 | 杭州盛弗泰新材料科技有限公司 | Synthetic method of p-hydroxyphenylethanol |
| CN111393264B (en) * | 2020-03-10 | 2022-07-15 | 杭州盛弗泰新材料科技有限公司 | Synthetic method of p-hydroxyphenylethanol |
| CN114790131A (en) * | 2021-01-25 | 2022-07-26 | 孚能科技(赣州)股份有限公司 | Positive electrode lithium supplement additive, positive electrode plate, preparation method of positive electrode plate and lithium ion battery |
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Application publication date: 20140521 |