CN108658730A - A kind of preparation method of p-fluorophenol - Google Patents
A kind of preparation method of p-fluorophenol Download PDFInfo
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- CN108658730A CN108658730A CN201810448002.5A CN201810448002A CN108658730A CN 108658730 A CN108658730 A CN 108658730A CN 201810448002 A CN201810448002 A CN 201810448002A CN 108658730 A CN108658730 A CN 108658730A
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- hydrobromic acid
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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
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
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Abstract
This application involves a kind of preparation method of p-fluorophenol, demethylating reaction occurs for p-Fluoroanisole and hydrobromic acid, generates p-fluorophenol and bromomethane.The p-fluorophenol of synthesis is detached by extracting process and reaction system；Raffinate is passed through the use of bromination hydrogen retrieval.The bromomethane that demethylating reaction generates is passed directly into the aqueous solution containing 15% pair of methyl sodium benzene sulphinate, generates chloroacetic acid；It isolates to obtaining sodium bromide after concentrated in the mother liquor after methyl methyl sulfone.Obtained sodium bromide can be used in the step of hydrogen bromide occurs.It has thus been inherently eliminated the discharge of acid-bearing wastewater and by-product, has reached the requirement of cleanly production.
Description
Technical field
The invention belongs to chemical technology fields, are related to a kind of synthetic method preparing p-fluorophenol.
Background technology
P-fluorophenol (4-Fluorophenol) is white crystals, relative density 1.1889,48.2 DEG C of fusing point, boiling point
185.6℃.It is toxic.It is corrosive.It is dissolved in water, is soluble in the organic solvents such as ethyl alcohol, ethyl acetate.
P-fluorophenol is mainly used for depressor Nebivolol, 5-HT1AReceptor anti-agent and anti-inflammatory, platelet aggregation-against, antibacterial
The synthesis of the drugs such as class；It is also used for synthesizing efficient herbicide flumicloracpentryl；It can be also used for the production of liquid crystal material.
According to the literature,
(1) one fluoride process of diazonium：Using paraphenetidine as raw material, mistake after diazo-reaction is carried out in fluoboric acid medium
Filter obtains its NITRODIAZONIUM FLUOROBORATE, and heating hydrolysis in hydrofluoric acid is put into after vacuum drying can obtain p-Fluoroanisole, then exist
It is heated to reflux and is hydrolyzed in dense hydrobromic acid, p-fluorophenol can be obtained.Extremely unstable NITRODIAZONIUM FLUOROBORATE is generated simultaneously,
There is prodigious danger in industrialized production.In addition, yield only has 30% or so.
(2) one Hydrolyze method of bromination：Using fluorobenzene as raw material, fluorobromobenzene is made through bromination, the latter is high in strong alkali solution
P-fluorophenol can be also made by being hydrolyzed under warm high pressure.This method inevitably will produce phenol, 4,4 '-difluorodiphenyl ethers and
The byproducts such as the fluoro- 4 '-dihydroxy diphenyl ethers of 4-, however phenol is the byproduct for being especially not intended to generate, because of its impossible essence
The method evaporated separates it.In addition, this method uses a large amount of bromines due to being needed when bromination, environmental pollution is caused.High temperature is high
The strong alkali solution of pressure is quite big to the corrosion of equipment.In addition, the etching problem of production equipment is also than more serious.
(3) diazonium one hydrolyzes hydroxylating method：, as raw material, p-fluoronitrobenzene is obtained through mixed acid nitrification to fluorine, to fluorine nitro
The hydrogenated reduction of benzene generates para-fluoroaniline.Para-fluoroaniline carries out diazo-reaction in acid medium and diazonium salt solution is made, after
Person heats hydrolysis and can be prepared by p-fluorophenol.The technique is using high-risk, high pollution units such as nitrification plus hydrogen, diazo-reactions
Process, the danger and wastewater discharge of production are very big.
The synthesis technology of above several p-fluorophenols, in safety, environmental protection etc., there are many hidden danger.
Improve product yield, simplify reaction step, prevent security risk, to react used catalyst and byproduct into
Row recovery reduces discharge, reduces the influence to environment, is the problem of modern chemical industry production must take into consideration.
The present invention is using p-Fluoroanisole as raw material, and demethylation, synthesizes p-fluorophenol in the presence of a catalyst.And to catalyst
Recovery, rationally utilizing etc. for by-product bromomethane test, and yield good result.Thus from basic
On eliminate the discharge of acid-bearing wastewater and by-product, reached the requirement of cleanly production.Figure of description is shown in technological process.
Invention content
In order to solve the problems in the prior art, the purpose of the present invention is to using p-Fluoroanisole and hydrobromic acid, in catalyst
In the presence of prepare p-fluorophenol synthetic method, it is characterized in that being made of following steps：
(1) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, addition 126g p-fluorophenyls methyl ether (1mol), one
48% quantitative hydrobromic acid and a small amount of phase transfer catalyst, under nitrogen protection strong stirring, heating are reacted at a certain temperature
After a period of time, it is cooled to room temperature.Reaction solution is extracted with 300ml, 200ml, 100ml benzene respectively, static 1 hour, is closed
And organic phase.Normal pressure recycles benzene, and decompression collects 80-85 DEG C/20mmHg fractions, obtains p-fluorophenol, content 99.2%, yield
96.4%.
(2) sodium bromide and concentrated phosphoric acid are added in proportion in 500ml reaction bulbs, heating distillation obtains not brominated bromination
Hydrogen.Bromination hydrogen is led in the raffinate of step (1), temperature control is at 10 DEG C hereinafter, measurement hydrobromic acid content, reaches
Stop being passed through hydrogen bromide when 48%.48% hydrobromic acid solution is directly used in step (1).
(3) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 179 grams are added to methyl sodium benzene sulphinate
(1mol), 600 grams of distilled water are being heated with stirring to reflux strongly, are being slowly introducing the bromomethane caused by step (1), have led to
Afterwards, continue reflux 2 hours, be cooled to room temperature.Filtering is washed, and vacuum drying is obtained to lauseto neu.
Raw material proportioning is in above-mentioned steps (1)：P-Fluoroanisole：Hydrobromic acid=1：2.0-5.0；It is preferred that 1:3.0-4.0
Above-mentioned hydrobromic acid is 48% hydrobromic acid aqueous solution；
Above-mentioned phase transfer catalyst is tetrabutylammonium bromide, methyltributylammonichloride chloride, cetyl trimethyl chlorination
Ammonium, preferably tetrabutylammonium bromide；Dosage 0.1-5%, preferably 0.5-1%；
Required 40-100 DEG C of the reaction temperature of above-mentioned steps (1), preferably 60-85 DEG C；
Above-mentioned steps (1) required reaction time 1-10 hours, preferably 2-5 hours；
Beneficial effects of the present invention：
With the demethylating reaction of Catalyzed By Phase-transfer Catalyst p-Fluoroanisole and hydrobromic acid, p-fluorophenol and bromine first are generated
Alkane reduces reaction temperature, shortens the reaction time.After the p-fluorophenol of synthesis is by benzene extracting process and reaction system separation
Feed liquid, by being passed through the not brominated hydrogen bromide synthesized by sodium bromide and concentrated phosphoric acid, when bromination hydrogen content reaches 48%
Wait can recovery, while remaining phase transfer catalyst in raffinate being retained in the solution again, is not required to when applying mechanically
Phase transfer catalyst is added again.The bromomethane (being gas at room temperature) that demethylating reaction generates is due to not soluble in water, in nitrogen
Driving under, separated in gaseous form with reaction system, be passed directly into and be previously heated to 90 DEG C, contain 15% pair of methylbenzene
In the aqueous solution of sulfinic acid sodium, methylation reaction occurs, generates chloroacetic acid, isolates in the mother liquor after methyl methyl sulfone
Only sodium bromide it is concentrated after obtain anhydrous sodium bromide, obtained sodium bromide can cover uses occur hydrogen bromide the step of in.This
Sample has just been inherently eliminated the discharge of acid-bearing wastewater and by-product, has reached the requirement of cleanly production.
Description of the drawings
Fig. 1 is the process diagram for synthesizing p-fluorophenol
Specific implementation mode
The content that following embodiment is used for further illustrating the present invention is not intended to limit the application of the present invention.In embodiment
Percentage is mass fraction without exception.
Embodiment 1
(1) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 126 grams of p-fluorophenyl methyl ethers (1mol) are added,
590 gram of 48% hydrobromic acid and 1 gram of phase transfer catalyst tetrabutylammonium bromide, under nitrogen protection strong stirring, heating, 80
DEG C reaction 3 hours after, be cooled to room temperature.Reaction solution is extracted with 300ml, 200ml, 100ml benzene respectively, static 1 hour,
Merge organic phase.Normal pressure recycles benzene, and decompression collects 80-85 DEG C/20mmHg fractions, obtains 108 grams of p-fluorophenols, content
99.2%, yield 96.4%.
(2) sodium bromide and concentrated phosphoric acid are added in proportion in 500ml reaction bulbs, heating distillation obtains not brominated bromination
Hydrogen.Bromination hydrogen is led in the raffinate of step (1), temperature control is at 10 DEG C hereinafter, measurement hydrobromic acid content, reaches
Stop being passed through hydrogen bromide when 48%.48% hydrobromic acid solution is directly used in step (1).
(3) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 179 grams are added to methyl sodium benzene sulphinate
(1mol), 600 grams of distilled water are being heated with stirring to reflux strongly, are being slowly introducing the bromomethane caused by step (1), have led to
Afterwards, continue reflux 2 hours, be cooled to room temperature.Filtering is washed, vacuum drying, obtains 135 grams to lauseto neu, content 96.7%,
Yield 80%.
Embodiment 2
(1) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 126 grams of p-fluorophenyl methyl ethers (1mol) are added,
650 gram of 48% hydrobromic acid and 1.3 grams of phase transfer catalyst tetrabutylammonium bromide, strong stirring under nitrogen protection, heating,
After 80 DEG C are reacted 3 hours, it is cooled to room temperature.Reaction solution is extracted with 300ml, 200ml, 100ml benzene respectively, static 1 is small
When, merge organic phase.Normal pressure recycles benzene, and decompression collects 80-85 DEG C/20mmHg fractions, obtains 107 grams of p-fluorophenols, content
99.4%, yield 95.4%.
(2) sodium bromide and concentrated phosphoric acid are added in proportion in 500ml reaction bulbs, heating distillation obtains not brominated bromination
Hydrogen.Bromination hydrogen is led in the raffinate of step (1), temperature control is at 10 DEG C hereinafter, measurement hydrobromic acid content, reaches
Stop being passed through hydrogen bromide when 48%.48% hydrobromic acid solution is directly used in step (1).
(3) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 179 grams are added to methyl sodium benzene sulphinate
(1mol), 600 grams of distilled water are being heated with stirring to reflux strongly, are being slowly introducing the bromomethane caused by step (1), have led to
Afterwards, continue reflux 2 hours, be cooled to room temperature.Filtering is washed, vacuum drying, obtains 140 grams to lauseto neu, content 97.2%,
Yield 83%.
The above embodiments merely illustrate the technical concept and features of the present invention, and its object is to allow the people for being familiar with this technology
Member can understand present disclosure, and it is not intended to limit the scope of the present invention.It is all according in spirit of that invention essence
The equivalence changes done and modification, should be covered by the protection scope of the present invention.
Claims (1)
1. synthetic method prepared by a kind of p-fluorophenol, it is characterized in that being made of following steps：
(1) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 126g p-fluorophenyl methyl ethers (1mo l) are added, centainly
48% hydrobromic acid and a small amount of phase transfer catalyst of amount, under nitrogen protection strong stirring, heating react one at a certain temperature
After the section time, it is cooled to room temperature.Reaction solution is extracted with 300ml, 200ml, 100ml benzene respectively, static 1 hour, is merged
Organic phase.Normal pressure recycles benzene, and decompression collects 80-85 DEG C/20mmHg fractions, obtains p-fluorophenol, content 99.2%, yield
96.4%.
(2) sodium bromide and concentrated phosphoric acid are added in proportion in 500ml reaction bulbs, heating distillation obtains not brominated hydrogen bromide.It will
Bromination hydrogen is led in the raffinate of step (1), and temperature control is at 10 DEG C hereinafter, hydrobromic acid content is measured, when reaching 48%
Stop being passed through hydrogen bromide.48% hydrobromic acid solution is directly used in step (1).
(3) in the 1000ml four-hole bottles equipped with thermometer and condenser pipe, 179 grams are added to methyl sodium benzene sulphinate (1mol),
600 grams of distilled water are being heated with stirring to reflux strongly, are being slowly introducing the bromomethane caused by step (1), after having led to, continue
Reflux 2 hours, is cooled to room temperature.Filtering is washed, and vacuum drying is obtained to lauseto neu.
Raw material proportioning is in above-mentioned steps (1)：P-Fluoroanisole：Hydrobromic acid=1：2.0-5.0；It is preferred that 1:3.0-4.0
Above-mentioned hydrobromic acid is 48% hydrobromic acid aqueous solution；
Above-mentioned phase transfer catalyst be tetrabutylammonium bromide, methyltributylammonichloride chloride, hexadecyltrimethylammonium chloride, it is excellent
Select tetrabutylammonium bromide；Dosage 0.1-5%, preferably 0.5-1%；
Required 40-100 DEG C of the reaction temperature of above-mentioned steps (1), preferably 60-85 DEG C；
Above-mentioned steps (1) required reaction time 1-10 hours, preferably 2-5 hours.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112010913A (en) * | 2019-05-31 | 2020-12-01 | 南京正大天晴制药有限公司 | Preparation method of 4-deoxy daunorubicin |
| CN113683491A (en) * | 2021-09-01 | 2021-11-23 | 王传良 | Preparation method of 4- (2-bromoethyl) phenol |
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| CN101648895A (en) * | 2009-08-31 | 2010-02-17 | 潍坊玉成化工有限公司 | Preparing method of para methyl p-tolyl sulfone |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112010913A (en) * | 2019-05-31 | 2020-12-01 | 南京正大天晴制药有限公司 | Preparation method of 4-deoxy daunorubicin |
| CN113683491A (en) * | 2021-09-01 | 2021-11-23 | 王传良 | Preparation method of 4- (2-bromoethyl) phenol |
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