CN108516930A - A kind of synthetic method of 4- fluorine phthalic acid - Google Patents
A kind of synthetic method of 4- fluorine phthalic acid Download PDFInfo
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- CN108516930A CN108516930A CN201810478172.8A CN201810478172A CN108516930A CN 108516930 A CN108516930 A CN 108516930A CN 201810478172 A CN201810478172 A CN 201810478172A CN 108516930 A CN108516930 A CN 108516930A
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- phthalic acid
- fluorine
- thionyl chloride
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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
- C07C51/04—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid halides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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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
- C07C51/58—Preparation of carboxylic acid halides
Abstract
The invention discloses a kind of synthetic methods of 4 fluorine phthalic acid, 4 nitrophthalic acid of raw material is dissolved in thionyl chloride and carries out chloride, denitration fluoro is carried out by dry fluorination reagent potassium fluoride after chloride, it adds thionyl chloride and removes the by-product generated in fluorination process, 4 fluorine phthalic acid of target compound is can be obtained after purification.The processing route of the present invention is simple, and the three wastes of generation are few, while efficiently solving the problems, such as that product is detached with solvent, and using 4 nitrophthalic acids as raw material, the raw material is cheap and easy to get；And during the synthetic method, chloride process uses thionyl chloride as solvent, obtained product yield high；Due to the influence of acyl chlorides, the energy consumption of fluoro denitration reaction is largely reduced, phase transfer catalyst is not needed not only, but also reaction temperature is milder, improves yield.
Description
Technical field
The present invention relates to compound synthesis fields, and in particular to the synthetic method of 4- fluorine phthalic acids.
Background technology
4- fluorine phthalic acid is widely used in fields such as medicine, pesticide, plastics, dyestuffs:Can be used as fluorochemical has
Machine intermediate, fluorine-containing substitute and fluorine-containing surfactant and a kind of for medicine, polymer, dyestuff and plasticizer
Intermediate, the document that it is studied by the country at present is fewer, and yield is also less high, therefore we study a kind of new 4- fluorine
The synthetic method of phthalic acid.
Invention content
The object of the present invention is to provide a kind of synthetic methods of new 4- fluorine phthalic acids.
To achieve the above object, the technical solution that the present invention takes is：
A kind of synthetic method of 4- fluorine phthalic acid, includes the following steps：
The synthesis of S1,4- nitro o-phthaloyl chloride
4- nitrophthalic acids 5g is placed in bottle with two necks, the thionyl chloride of 12ml is added at one time, stirring is warming up to
78 DEG C, flow back 15min after, raw material all dissolve, continue at this temperature flow back 3h, stop reaction, stand cooling, with decompression steam
Distillation unit steams extra thionyl chloride, and a large amount of pale yellow powder is precipitated later, is dried to obtain by vacuum drying chamber
4.25g 4- nitro o-phthaloyl chlorides；
The synthesis of S2,4- fluorine O-phthalic acyl fluorides
4- nitro o-phthaloyl chlorides 1g, dried KF 0.7g, sulfolane 2.5ml are placed in bottle with two necks, oil bath dress
It sets down after being heated with stirring to 130 DEG C of reaction 2h, stops reaction, after cooling, the thionyl chloride of addition 0.5ml into reaction solution, 78
Flow back 30min at DEG C, and extra thionyl chloride is evaporated under reduced pressure and is removed；Then 0.5ml sulfolane, 0.5g are added into bottle with two necks
Potassium fluoride is heated to 130 DEG C, and generating unit dividend Brown gas, after reacting 1.5h, no rufous gas generates, and stops reaction, obtains
Reaction solution；
The synthesis of S3,4- fluorine phthalic acid.
Preferably, the step S3 specifically comprises the following steps：
A certain amount of water is added into the reaction solution obtained by step S2, until the powder in solution disappears, adjusts liquid PH
To alkalinity, after ethyl acetate extracts 3 times, water phase is adjusted into PH to acidity, ethyl acetate extracts 3 times again, is evaporated under reduced pressure to get 4-
Fluorine phthalic acid.
Preferably, the step S3 specifically comprises the following steps：
Reaction solution obtained by step S2 is filtered, after filter residue is washed by ethyl acetate, vacuum distillation removes extra second
Acetoacetic ester adjusts liquid PH to alkalinity, after ethyl acetate extracts 3 times, water phase is adjusted PH to acidity, ethyl acetate extracts 3 again
It is secondary, it is evaporated under reduced pressure to get 4- fluorine phthalic acids.
Wherein, the absorption plant of the sodium hydroxide solution in the step S1 equipped with saturation between distilling apparatus and water pump is inhaled
Thionyl chloride gas is received, prevents the pump housing from damaging.
Wherein, a large amount of rufous gas is generated after reacting 30min in the step S2, the gas of generation is passed through quality
The sodium hydroxide solution that score is 30% carries out tail gas absorption.
Wherein, the dosage of each ethyl acetate extraction is 50ml.
The invention has the advantages that：
The processing route of the present invention is simple, and the three wastes of generation are few, at the same it is efficient solve that product detaches with solvent ask
Topic, using 4- nitrophthalic acids as raw material, the raw material is cheap and easy to get；And during the synthetic method, chloride process uses
Thionyl chloride is as solvent, obtained product yield high；Due to the influence of acyl chlorides, fluoro denitration reaction is largely reduced
Energy consumption, do not need phase transfer catalyst not only, but also reaction temperature is milder, improve yield.
Description of the drawings
Fig. 1 is the synthetic line figure of step S1 in the embodiment of the present invention.
Fig. 2 is the synthetic line figure of step S2 in the embodiment of the present invention.
Fig. 3 is the synthetic line figure of step S3 in the embodiment of the present invention.
Fig. 4 is the whole synthetic line figure of the embodiment of the present invention.
Specific implementation mode
In order to make objects and advantages of the present invention be more clearly understood, the present invention is carried out with reference to embodiments further
It is described in detail.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to limit this hair
It is bright.
Embodiment 1
A kind of synthetic method of 4- fluorine phthalic acid, includes the following steps：
The synthesis of S1,4- nitro o-phthaloyl chloride
4- nitrophthalic acids 5g (0.0237mol) is placed in bottle with two necks, 12ml (0.165mol) is added at one time
Thionyl chloride, stirring is warming up to 78 DEG C, and after the 15min that flows back, raw material all dissolves, and continues the 3h that flows back at this temperature, stops
Reaction stands cooling, is steamed extra thionyl chloride (equipped with saturation between distilling apparatus and water pump with vacuum distillation apparatus
The absorption plant of sodium hydroxide solution absorbs thionyl chloride gas, prevents the pump housing from damaging), a large amount of yellowish toner is precipitated later
End is dried to obtain 4- nitro o-phthaloyl chloride 4.25g (0.022mol), yield 93% by vacuum drying chamber；
The synthesis of S2,4- fluorine O-phthalic acyl fluorides
The sulfolane of 4- nitro o-phthaloyl chloride 1g (4mmol), dried KF 0.7g (12mmol), 2.5ml are set
In bottle with two necks, it is heated with stirring to 130 DEG C under oil bath device, a large amount of rufous gas is generated after 30min, by the gas of generation
It is passed through the sodium hydroxide solution that mass fraction is 30% and carries out tail gas absorption.Stop reacting after reacting 2h, after cooling, passes through nuclear-magnetism
Data find that the ratio of raw material and product is 0.5:1, conversion ratio 67%.After analysis, by-product is produced in the reaction process
By-product is become raw material progress next step reaction by object by the way that thionyl chloride is added again, and reaction process is as follows:
Again into reaction solution be added 0.5ml thionyl chloride (for removing the by-product generated in reaction process), 78 DEG C
Extra thionyl chloride is evaporated under reduced pressure and removes by lower reflux 30min.0.5ml sulfolane, 0.5g fluorine is added into bottle with two necks again
Change potassium, is heated to 130 DEG C, while generating unit dividend Brown gas, after reacting 1.5h, no rufous gas generates, and stops reaction,
It takes a small amount of reaction solution to carry out nuclear-magnetism detection, finds almost without raw material, conversion ratio 95%.
The synthesis of S2,4- fluorine phthalic acid
A part of water is added into reaction solution, until the powder in solution disappears, adjusts liquid PH to alkalinity, passes through acetic acid
Ethyl ester (3 × 50ml) comes out the sulfolane extraction in solution, then water phase is adjusted PH to acidity, by ethyl acetate (3 ×
50ml) product in water phase is extracted, organic solution is evaporated under reduced pressure to obtain product 4- fluorine phthalic acids 0.59g
(3.2mmol), yield 80%；Obtained product is pale yellow powder,1H NMR(CDCl3,400MHz)δ:8.26 (d, J=
8.0Hz, 2H), 8.78 (dd, J=8.0Hz, 1H), 8.84 (d, J=4.0Hz, 1H)；13C NMR(CDCl3,100MHz)δ:
(121.14,127.25,131.09,132.78,135.43,152.81,160.29,160.58)。
Embodiment 2
A kind of synthetic method of 4- fluorine phthalic acid, includes the following steps：
The synthesis of S1,4- nitro o-phthaloyl chloride
4- nitrophthalic acids 5g (0.0237mol) is placed in bottle with two necks, 12ml (0.165mol) is added at one time
Thionyl chloride, stirring is warming up to 78 DEG C, and after the 15min that flows back, raw material all dissolves, and continues the 3h that flows back at this temperature, stops
Reaction stands cooling, is steamed extra thionyl chloride (equipped with saturation between distilling apparatus and water pump with vacuum distillation apparatus
The absorption plant of sodium hydroxide solution absorbs thionyl chloride gas, prevents the pump housing from damaging), a large amount of yellowish toner is precipitated later
End is dried to obtain 4- nitro o-phthaloyl chloride 4.25g (0.022mol), yield 93% by vacuum drying chamber；
The synthesis of S2,4- fluorine O-phthalic acyl fluorides
The sulfolane of 4- nitro o-phthaloyl chloride 1g (4mmol), dried KF 0.7g (12mmol), 2.5ml are set
In bottle with two necks, it is heated with stirring to 130 DEG C under oil bath device, a large amount of rufous gas is generated after 30min, by the gas of generation
It is passed through the sodium hydroxide solution that mass fraction is 30% and carries out tail gas absorption.Stop reacting after reacting 2h, after cooling, passes through nuclear-magnetism
Data find that the ratio of raw material and product is 0.5:1, conversion ratio 67%.After analysis, by-product is produced in the reaction process
By-product is become raw material progress next step reaction by object by the way that thionyl chloride is added again, and reaction process is as follows:
Again into reaction solution be added 0.5ml thionyl chloride (for removing the by-product generated in reaction process), 78 DEG C
Extra thionyl chloride is evaporated under reduced pressure and removes by lower reflux 30min.0.5ml sulfolane, 0.5g fluorine is added into bottle with two necks again
Change potassium, is heated to 130 DEG C, while generating unit dividend Brown gas, after reacting 1.5h, no rufous gas generates, and stops reaction,
A small amount of progress nuclear-magnetism detection is taken, is found almost without raw material, conversion ratio 95%.
The synthesis of S2,4- fluorine phthalic acid
First reaction solution is filtered, filter residue is washed by ethyl acetate, is evaporated under reduced pressure extra ethyl acetate removes later,
Liquid PH is adjusted to alkalinity, is come out the sulfolane extraction in solution by ethyl acetate (3 × 50ml), then water phase is adjusted into PH
To acidity, the product in water phase is extracted by ethyl acetate (3 × 50ml), organic solution is evaporated under reduced pressure to obtain product
4- fluorine phthalic acid 0.54g (2.93mmol), yield 73%；Obtained product is pale yellow powder,1H NMR(CDCl3,
400MHz)δ:(8.26 d, J=8.0Hz, 2H), 8.78 (dd, J=8.0Hz, 1H), 8.84 (d, J=4.0Hz, 1H)；13C NMR
(CDCl3,100MHz)δ:(121.14,127.25,131.09,132.78,135.43,152.81,160.29,160.58)。
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the principle of the present invention, it can also make several improvements and retouch, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (6)
1. a kind of synthetic method of 4- fluorine phthalic acid, which is characterized in that include the following steps：
The synthesis of S1,4- nitro o-phthaloyl chloride
4- nitrophthalic acids 5g is placed in bottle with two necks, the thionyl chloride of 12ml is added at one time, stirring is warming up to 78 DEG C,
It flows back after 15min, raw material all dissolves, and continues the 3h that flows back at this temperature, stops reaction, stands cooling, is filled with vacuum distillation
It sets and steams extra thionyl chloride, a large amount of pale yellow powder is precipitated later, 4.25g is dried to obtain by vacuum drying chamber
4- nitro o-phthaloyl chlorides；
The synthesis of S2,4- fluorine O-phthalic acyl fluorides
4- nitro o-phthaloyl chlorides 1g, dried KF 0.7g, sulfolane 2.5ml are placed in bottle with two necks, under oil bath device
After being heated with stirring to 130 DEG C of reaction 2h, stop reaction, after cooling, the thionyl chloride of addition 0.5ml into reaction solution, at 78 DEG C
Flow back 30min, and extra thionyl chloride is evaporated under reduced pressure and is removed；Then 0.5ml sulfolane, 0.5g fluorinations are added into bottle with two necks
Potassium is heated to 130 DEG C, and generating unit dividend Brown gas, after reacting 1.5h, no rufous gas generates, and stops reaction, must react
Liquid；
The synthesis of S3,4- fluorine phthalic acid.
2. a kind of synthetic method of 4- fluorine phthalic acid as described in claim 1, which is characterized in that the step S3 is specific
Include the following steps：
A certain amount of water is added into the reaction solution obtained by step S2, until the powder in solution disappears, adjusts liquid PH to alkali
Property, after ethyl acetate extracts 3 times, water phase is adjusted into PH to acidity, ethyl acetate extracts 3 times again, and vacuum distillation is adjacent to get 4- fluorine
Phthalic acid.
3. a kind of synthetic method of 4- fluorine phthalic acid as described in claim 1, which is characterized in that the step S3 is specific
Include the following steps：
Reaction solution obtained by step S2 is filtered, after filter residue is washed by ethyl acetate, vacuum distillation removes extra acetic acid second
Ester adjusts liquid PH to alkalinity, after ethyl acetate extracts 3 times, water phase is adjusted PH to acidity, ethyl acetate extracts 3 times again, subtracts
Pressure distillation is to get 4- fluorine phthalic acids.
4. a kind of synthetic method of 4- fluorine phthalic acid as described in claim 1, which is characterized in that steamed in the step S1
The absorption plant of sodium hydroxide solution equipped with saturation between distillation unit and water pump absorbs thionyl chloride gas, prevents the pump housing from damaging
It is bad.
5. a kind of synthetic method of 4- fluorine phthalic acid as described in claim 1, which is characterized in that anti-in the step S2
Generate a large amount of rufous gas after answering 30min, by the gas of generation be passed through mass fraction be 30% sodium hydroxide solution into
End of line aspiration.
6. such as a kind of synthetic method of 4- fluorine phthalic acid of Claims 2 or 3 any one of them, which is characterized in that every time
The dosage of ethyl acetate extraction is 50ml.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868415A (en) * | 1973-10-03 | 1975-02-25 | Merck & Co Inc | Preparation of 5-fluoro-2-methyl-1-(p-methyl-sulfinylbenzylidene)-indenyl-3-acetic acid |
| US5405995A (en) * | 1994-06-20 | 1995-04-11 | Occidental Chemical Corporation | Difluorophthalic compounds and their preparation |
| EP1598331A1 (en) * | 2004-05-17 | 2005-11-23 | Lanxess Deutschland GmbH | Process for the preparation of phthalic acid dichloride |
| CN101967111A (en) * | 2009-12-16 | 2011-02-09 | 辽宁师范大学 | 5-(4-hydroxyphenyl azo)-1,3-phthaloyl glycine and preparation method thereof |
| CN104003868A (en) * | 2014-05-26 | 2014-08-27 | 中国平煤神马能源化工集团有限责任公司技术中心 | Preparation and purification method of paraphthaloyl chloride with high purity |
-
2018
- 2018-05-18 CN CN201810478172.8A patent/CN108516930A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3868415A (en) * | 1973-10-03 | 1975-02-25 | Merck & Co Inc | Preparation of 5-fluoro-2-methyl-1-(p-methyl-sulfinylbenzylidene)-indenyl-3-acetic acid |
| US5405995A (en) * | 1994-06-20 | 1995-04-11 | Occidental Chemical Corporation | Difluorophthalic compounds and their preparation |
| EP1598331A1 (en) * | 2004-05-17 | 2005-11-23 | Lanxess Deutschland GmbH | Process for the preparation of phthalic acid dichloride |
| CN101967111A (en) * | 2009-12-16 | 2011-02-09 | 辽宁师范大学 | 5-(4-hydroxyphenyl azo)-1,3-phthaloyl glycine and preparation method thereof |
| CN104003868A (en) * | 2014-05-26 | 2014-08-27 | 中国平煤神马能源化工集团有限责任公司技术中心 | Preparation and purification method of paraphthaloyl chloride with high purity |
Non-Patent Citations (4)
| Title |
|---|
| DAVID J. MILNER: ""An Improved Procedure for the Synthesis of 3-Fluoroanthranilic Acid"", 《SYNTHETIC COMMUNICATIONS》 * |
| P. MARGHERITA ET AL.: ""A New Synthesis of 3-Fluorophthalic Anhydride"", 《JOURNAL OF FLUORINE CHEMISTRY》 * |
| 李学敏等: ""有机化合物的氟化反应研究进展"", 《精细与专用化学品》 * |
| 江体乾: "《化工工艺手册》", 29 February 1992, 上海科学技术出版社 * |
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