CN106336352A - Synthesis method of 6-fluorosalicylic acid - Google Patents
Synthesis method of 6-fluorosalicylic acid Download PDFInfo
- Publication number
- CN106336352A CN106336352A CN201610745061.XA CN201610745061A CN106336352A CN 106336352 A CN106336352 A CN 106336352A CN 201610745061 A CN201610745061 A CN 201610745061A CN 106336352 A CN106336352 A CN 106336352A
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- acid
- water
- value
- fluorosalicylic
- solid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
Abstract
The invention discloses a synthesis method of 6-fluorosalicylic acid, and belongs to the field of preparation of fine chemical compounds. The method includes the steps of mixing 2,6-difluorobenzonitrile, sodium hydroxide and water for reaction under the pressure of 0.25 MPa at the temperature of 150 DEG C, cooling and then adjusting the pH value of reaction liquid through acid liquor, taking out separated solid, washing and drying the solid, dissolving the solid in solvent for recrystallization, and obtaining 6-fluorosalicylic acid. The method is characterized in that the mixing molar ratio of 2,6-difluorobenzonitrile to sodium hydroxide to water is 1:3:10; the acid liquor for adjusting the pH value of the reaction liquid is a sulfuric acid aqueous solution and is used for adjusting the pH value to be 1; the solvent for recrystallization is an ethyl alcohol and water mixed solution. The method is low in production cost and high in yield.
Description
Technical field
The invention belongs to fine chemistry industry field of compound preparation.
Background technology
At present, the introduction to 6- fluorosalicylic acid both at home and abroad and synthetic method are little, according to other halogenation physical property salicylic
Matter and feature, can think deeply 6- fluorosalicylic acid and have very big utilization in terms of medicine and pesticide, such as 5- fluorosalicylic acid
It is that important Drugs Containing Fluorine intermediate ankenbauer etc. constructs salicylic acid synthesis blocking-up mutant sal-ia602,5- fluorine
Salicylic synthetic route fig 1 synthetic route of 5-fluoro-2-chlorobenzonitrile only finds
There is 5- fluorosalicylic acid etc. could generate corresponding microbial medicine, water in the biosynthesiss for pyochelin analog
Poplar acid halogenide has so big importance in this regard it is therefore desirable to further research and develop and break through.
Document discloses a kind of 6- fluorosalicylic acid production method, by 2,6- difluorobenzonilyile, sodium hydroxide and water with 1:2.5:
3 mixed in molar ratio post-heating flows back 3 hours, obtains 2,6- difluoro-benzoic acid sodium solution；Again pressure be 0.25mpa, temperature be
Under the conditions of 150 DEG C, reacting by heating is carried out to 2,6- difluoro-benzoic acid sodium solution；Adjust ph value to 2-3 with hydrochloric acid after reaction, separate out slightly
Band faint yellow solid, is carried out washing to solid, is dried with cold water, then again with toluene recrystallization obtains white crystals 6- fluorine bigcatkin willow
Acid.This method needs two and completes, and so that production is complicated, yield is low, increased cost.
Content of the invention
For the defect that existing production method exists above, the present invention seeks to proposing a kind of One-step production 6- fluorine water
The method of poplar acid, to reduce production cost, improves yield.
The technical scheme is that: by 2,6- difluorobenzonilyile, sodium hydroxide and water mix after 0.25mpa pressure, 150
React under the conditions of DEG C, after cooling, reactant liquor adjusted ph value with acid solution, obtain and separate out solid, take the washing of described solid, after drying,
Again solid is dissolved in recrystallization in solvent, obtains 6- fluorosalicylic acid；Its characteristic point is: described 2,6- difluorobenzonilyile, hydroxide
The mixing mol ratio of sodium and water is 1: 3: 10；Acid solution for reactant liquor is adjusted with ph value is aqueous sulfuric acid, and ph value is adjusted to
1；Solvent for recrystallization is ethanol and water mixed solution.
Contrast with existing method from above method, be only that the mixing ratio of raw material is different, the acid of whole ph value is changed to by hydrochloric acid
Sulphuric acid, ph value adjustment difference, the solvent difference of recrystallization.
What this invention embodied is that single step reaction generates 6- fluorosalicylic acid, and does not need to previously generate 2,6- difluorobenzene first
Sour sodium, simplifies process units.
In addition, because this cyan-hydrolysis becomes carboxyl to need finite concentration sodium hydrate aqueous solution, when only adding 2.5 times of equivalents
Sodium hydroxide when, also small part cyano group cannot hydrolyze, and increased the impurity of product, so the present invention adopts 2,6- difluoro
The mixing mol ratio of cyanophenyl, sodium hydroxide and water adopts 1: 3: 10, suitably increases sodium hydrate content, is to make raw material completely anti-
Should.
The present invention adjusts ph value to 1 using aqueous sulfuric acid, makes system become acid state, so can make 6- fluorosalicylic acid
Crystal separates out completely.
Because ethanol is volatile, the residual of the product ethanol after recrystallization is few, and with re crystallization from toluene, in possible product, meeting is residual
Stay toluene, the quality index of product is had an impact.Therefore recrystallization of the present invention when adopt ethanol and water mixed solution.
In addition, the present invention obtains target product using one-step method pressurized hydrolysis, post processing is simple, and purity may be up to purity
98%, yield can reach 85%
Further, sulphuric acid is for regulation system ph value, and use quality percent is 10% concentrated sulphuric acid, is for ease of control volume
The ph value of system.
Further, in described ethanol and water mixed solution the mixed volume of second alcohol and water than for 2: 1.6- fluorosalicylic acid is micro-
Be dissolved in cold water, ethanol can dissolved impurity very well, so having good refining effect with the mixed solution recrystallization of both.
Specific embodiment
(consumption of three rubs to add 139g 2,6- difluorobenzonilyile, 120g sodium hydroxide and 180g water to autoclave pressure
That ratio is: 1: 3: 10), is heated to 150 DEG C, reacts 10 hours, control pressure is 0.25mpa.
Reaction cools down after terminating, and reactant liquor is poured in beaker, is that 10% aqueous sulfuric acid adjusts ph value with mass percent
To 1, separate out slightly faint yellow solid.Through sucking filtration, take solid phase cold water to wash, dry, then with 300ml ethanol and water volume ratio be
The mixed solution recrystallization of 2:1 obtains white crystals 6- fluorosalicylic acid 168.2g.
The yield of 6- fluorosalicylic acid is: 85%.
The purity of 6- fluorosalicylic acid is: 98.5%.
Claims (3)
- A kind of synthetic method of 1.6- fluorosalicylic acid, in 0.25mpa pressure after 2,6- difluorobenzonilyile, sodium hydroxide and water are mixed Power, react under the conditions of 150 DEG C, after cooling, reactant liquor is adjusted ph value with acid solution, obtain and separate out solid, take described solid to wash, After drying, then solid is dissolved in recrystallization in solvent, obtains 6- fluorosalicylic acid；It is characterized in that described 2,6- difluorobenzonilyile, The mixing mol ratio of sodium hydroxide and water is 1: 3: 10；Acid solution for reactant liquor is adjusted with ph value is aqueous sulfuric acid, by ph Value is adjusted to 1；Solvent for recrystallization is ethanol and water mixed solution.
- 2. according to claim 1 a kind of synthetic method of 6- fluorosalicylic acid it is characterised in that the matter of described aqueous sulfuric acid Amount percent is 10%.
- 3. a kind of synthetic method of 6- fluorosalicylic acid according to claim 1 or claim 2 is it is characterised in that described second alcohol and water mixes In solution, the mixed volume of second alcohol and water is than for 2: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610745061.XA CN106336352A (en) | 2016-08-29 | 2016-08-29 | Synthesis method of 6-fluorosalicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610745061.XA CN106336352A (en) | 2016-08-29 | 2016-08-29 | Synthesis method of 6-fluorosalicylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106336352A true CN106336352A (en) | 2017-01-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201610745061.XA Pending CN106336352A (en) | 2016-08-29 | 2016-08-29 | Synthesis method of 6-fluorosalicylic acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115260010A (en) * | 2021-04-29 | 2022-11-01 | 新岸诺亚（北京）催化科技有限公司 | Method for preparing m-fluorophenol from 2, 6-difluorobenzonitrile |
| CN115260009A (en) * | 2021-04-29 | 2022-11-01 | 新岸诺亚（北京）催化科技有限公司 | Preparation method of m-fluorophenol |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293700A (en) * | 1993-04-08 | 1994-10-21 | Nippon Soda Co Ltd | Production of 6-salicylic acid |
| CN102320960A (en) * | 2011-08-02 | 2012-01-18 | 安徽东健化工科技有限公司 | Preparation method of 6-fluoro salicylic acid |
-
2016
- 2016-08-29 CN CN201610745061.XA patent/CN106336352A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06293700A (en) * | 1993-04-08 | 1994-10-21 | Nippon Soda Co Ltd | Production of 6-salicylic acid |
| CN102320960A (en) * | 2011-08-02 | 2012-01-18 | 安徽东健化工科技有限公司 | Preparation method of 6-fluoro salicylic acid |
Non-Patent Citations (1)
| Title |
|---|
| 陈红飙等: "5-氟水杨酸的合成", 《湘潭大学自然科学学报》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115260010A (en) * | 2021-04-29 | 2022-11-01 | 新岸诺亚（北京）催化科技有限公司 | Method for preparing m-fluorophenol from 2, 6-difluorobenzonitrile |
| CN115260009A (en) * | 2021-04-29 | 2022-11-01 | 新岸诺亚（北京）催化科技有限公司 | Preparation method of m-fluorophenol |
| CN115260009B (en) * | 2021-04-29 | 2023-11-24 | 新岸诺亚（北京）催化科技有限公司 | Preparation method of m-fluorophenol |
| CN115260010B (en) * | 2021-04-29 | 2023-11-24 | 新岸诺亚（北京）催化科技有限公司 | Method for preparing m-fluorophenol from 2, 6-difluorobenzonitrile |
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Application publication date: 20170118 |
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