CN102320960A - Preparation method of 6-fluoro salicylic acid - Google Patents
Preparation method of 6-fluoro salicylic acid Download PDFInfo
- Publication number
- CN102320960A CN102320960A CN201110218286A CN201110218286A CN102320960A CN 102320960 A CN102320960 A CN 102320960A CN 201110218286 A CN201110218286 A CN 201110218286A CN 201110218286 A CN201110218286 A CN 201110218286A CN 102320960 A CN102320960 A CN 102320960A
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- Prior art keywords
- preparation
- salicylic acid
- acid
- solution
- water
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- BCEKGWWLVKXZKK-UHFFFAOYSA-N 2-fluoro-6-hydroxybenzoic acid Chemical compound OC(=O)C1=C(O)C=CC=C1F BCEKGWWLVKXZKK-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 239000007787 solid Substances 0.000 claims abstract description 4
- 238000000967 suction filtration Methods 0.000 claims abstract description 4
- 238000005406 washing Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 6
- WNIQENZFLQALAX-UHFFFAOYSA-N [Na].OC(=O)C1=C(F)C=CC=C1F Chemical compound [Na].OC(=O)C1=C(F)C=CC=C1F WNIQENZFLQALAX-UHFFFAOYSA-N 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract 2
- BNBRIFIJRKJGEI-UHFFFAOYSA-N 2,6-difluorobenzonitrile Chemical compound FC1=CC=CC(F)=C1C#N BNBRIFIJRKJGEI-UHFFFAOYSA-N 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000000575 pesticide Substances 0.000 abstract 1
- 230000001376 precipitating effect Effects 0.000 abstract 1
- NSAGNHHXPUCREY-UHFFFAOYSA-M sodium;2,6-difluorobenzoate Chemical compound [Na+].[O-]C(=O)C1=C(F)C=CC=C1F NSAGNHHXPUCREY-UHFFFAOYSA-M 0.000 abstract 1
- JWPRICQKUNODPZ-UHFFFAOYSA-N 5-fluoro-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1O JWPRICQKUNODPZ-UHFFFAOYSA-N 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 3
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
- HBTXAKDVIXNVHZ-UHFFFAOYSA-N 2-chloro-5-fluorobenzonitrile Chemical compound FC1=CC=C(Cl)C(C#N)=C1 HBTXAKDVIXNVHZ-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 101150004367 Il4i1 gene Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- NYBZAGXTZXPYND-GBIKHYSHSA-N pyochelin I Chemical class S1C[C@@H](C(O)=O)N(C)[C@H]1[C@@H]1N=C(C=2C(=CC=CC=2)O)SC1 NYBZAGXTZXPYND-GBIKHYSHSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 6-fluoro salicylic acid. The preparation method comprises the following steps of: adding 2,6-difluorobenzonitrile, sodium hydroxide and water in a certain ratio to a flask, and heating to obtain a sodium 2,6-difluorobenzoate solution; and then pouring the solution into a pressure kettle, heating and reacting, adjusting the pH value to 2-3 with hydrochloric acid, precipitating white solid, carrying out suction filtration, washing with cold water, drying and recrystallizing with toluene to obtain white crystal 6-fluoro salicylic acid. 6-fluoro salicylic acid disclosed by the invention is a novel compound which is not recorded in existing literature, and is a very useful intermediate in the aspects of drugs, pesticides, and the like; and the preparation method is simple and is low in cost.
Description
Technical field
The present invention relates to a kind of preparation method of 6-fluorosalicylic acid, belong to fine chemistry industry compound field.
Background technology
At present; Both at home and abroad seldom to the introduction of 6-fluorosalicylic acid and compound method; According to salicylic other halogenide character and characteristics; Can think deeply and the 6-fluorosalicylic acid and have very big utilization aspect medicine and the agricultural chemicals; Made up the synthetic blocking-up of Whitfield's ointment two mutants Sal-IA602 such as the 5-fluorosalicylic acid is important fluorine-containing pharmaceutical intermediate Ankenbauer etc., the synthetic route Fig1 Synthetic route of 5-fluoro-2-chlorobenzonitrile of 5-fluorosalicylic acid finds to have only 5-fluorosalicylic acid etc. to generate corresponding microbial medicine in the biosynthesizing that is used for the pyochelin analogue; Whitfield's ointment halogenide has so big importance in this regard, therefore needs further to research and develop and break through.
Summary of the invention
In order further breakthrough to be arranged, the object of the present invention is to provide a kind of preparation method of 6-fluorosalicylic acid in the research aspect agricultural chemicals and the medicine.
The present invention adopts following technical scheme to achieve these goals:
The preparation method of 6-fluorosalicylic acid is characterized in that may further comprise the steps:
(1) in flask, add 2 of certain proportioning, 6-difluorobenzonilyile, sodium hydroxide and water, reflux 3 hours gets 2,6-difluoro-benzoic acid sodium solution;
(2) above-mentioned solution is poured in the autoclave pressure, be heated to 140-160 ℃ of reaction 5 hours, control pressure is about 0.25MPa; After the cooling reaction solution is poured in the beaker, transferred pH value to 2-3, separate out white solid with hydrochloric acid; Suction filtration; Use cold water washing, oven dry gets white crystals 6-fluorosalicylic acid with 280-320ml toluene recrystallization again.
The preparation method of described 6-fluorosalicylic acid is characterized in that: described 2, the proportioning of 6-difluorobenzonilyile, sodium hydroxide and water is 1:2.5:2.7-3.0.
Beneficial effect of the present invention:
6-fluorosalicylic acid of the present invention is a novel cpd of not seeing the document record, be very useful as intermediates of medicine and agricultural chemicals and other a lot of aspects, and preparation method of the present invention is simple, and cost is low.
Embodiment
Embodiment:The preparation method of 6-fluorosalicylic acid may further comprise the steps:
(1) in the 1L flask, add 139g 2,6-difluorobenzonilyile, 100g sodium hydroxide and 500g water, reflux 3 hours gets 2,6-difluoro-benzoic acid sodium solution;
(2) above-mentioned solution is poured in the autoclave pressure, be heated to 150 ℃ of reactions 5 hours, control pressure 0.25MPa; After the cooling reaction solution is poured in the beaker, transferred pH value to 2-3, separate out white solid with hydrochloric acid; Suction filtration; Use cold water washing, oven dry gets white crystals 6-fluorosalicylic acid 80g with 300ml toluene recrystallization again.
Claims (2)
1. the preparation method of a 6-fluorosalicylic acid is characterized in that may further comprise the steps:
(1) in flask, add 2 of certain proportioning, 6-difluorobenzonilyile, sodium hydroxide and water, reflux 3 hours gets 2,6-difluoro-benzoic acid sodium solution;
(2) above-mentioned solution is poured in the autoclave pressure, be heated to 140-160 ℃ of reaction 5 hours, control pressure is about 0.25MPa; After the cooling reaction solution is poured in the beaker, transferred pH value to 2-3, separate out white solid with hydrochloric acid; Suction filtration; Use cold water washing, oven dry gets white crystals 6-fluorosalicylic acid with 280-320ml toluene recrystallization again.
2. the preparation method of 6-fluorosalicylic acid according to claim 1 is characterized in that: described 2, the proportioning of 6-difluorobenzonilyile, sodium hydroxide and water is 1:2.5:2.7-3.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110218286A CN102320960A (en) | 2011-08-02 | 2011-08-02 | Preparation method of 6-fluoro salicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110218286A CN102320960A (en) | 2011-08-02 | 2011-08-02 | Preparation method of 6-fluoro salicylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102320960A true CN102320960A (en) | 2012-01-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110218286A Pending CN102320960A (en) | 2011-08-02 | 2011-08-02 | Preparation method of 6-fluoro salicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102320960A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103224451A (en) * | 2013-05-20 | 2013-07-31 | 山东潍坊润丰化工有限公司 | Method for synthesizing 3,5-dichlorobenzoic acid |
| CN103242190A (en) * | 2013-05-20 | 2013-08-14 | 山东潍坊润丰化工有限公司 | Synthetic method of propyzamide |
| CN106336352A (en) * | 2016-08-29 | 2017-01-18 | 扬州天辰精细化工有限公司 | Synthesis method of 6-fluorosalicylic acid |
| JP2020536861A (en) * | 2017-10-11 | 2020-12-17 | キューペックス バイオファーマ， インコーポレイテッド | Boronic acid derivatives and their synthesis |
| US11180512B2 (en) | 2016-06-30 | 2021-11-23 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| 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 |
| CN117796401A (en) * | 2023-12-25 | 2024-04-02 | 江苏万隆化学有限公司 | Preparation process of an intermediate antibacterial agent containing 2-hydroxy-6-fluorobenzoic acid methyl ester |
| US12016868B2 (en) | 2018-04-20 | 2024-06-25 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1206399A (en) * | 1996-10-18 | 1999-01-27 | 伊哈拉化学工业株式会社 | 4-fluorosalicylic acid derivative and its preparation method |
-
2011
- 2011-08-02 CN CN201110218286A patent/CN102320960A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1206399A (en) * | 1996-10-18 | 1999-01-27 | 伊哈拉化学工业株式会社 | 4-fluorosalicylic acid derivative and its preparation method |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103242190A (en) * | 2013-05-20 | 2013-08-14 | 山东潍坊润丰化工有限公司 | Synthetic method of propyzamide |
| CN103242190B (en) * | 2013-05-20 | 2015-03-25 | 山东潍坊润丰化工股份有限公司 | Synthetic method of propyzamide |
| CN103224451A (en) * | 2013-05-20 | 2013-07-31 | 山东潍坊润丰化工有限公司 | Method for synthesizing 3,5-dichlorobenzoic acid |
| US11180512B2 (en) | 2016-06-30 | 2021-11-23 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| US11999759B2 (en) | 2016-06-30 | 2024-06-04 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| US12509475B2 (en) | 2016-06-30 | 2025-12-30 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| CN106336352A (en) * | 2016-08-29 | 2017-01-18 | 扬州天辰精细化工有限公司 | Synthesis method of 6-fluorosalicylic acid |
| EP3694864A4 (en) * | 2017-10-11 | 2021-10-13 | Qpex Biopharma, Inc. | BORONIC ACID DERIVATIVES AND SYNTHESIS OF THESE LATEST |
| KR20210005540A (en) * | 2017-10-11 | 2021-01-14 | 큐펙스 바이오파마 인코포레이티드 | Boronic acid derivatives and their synthesis |
| JP2020536861A (en) * | 2017-10-11 | 2020-12-17 | キューペックス バイオファーマ， インコーポレイテッド | Boronic acid derivatives and their synthesis |
| TWI800539B (en) * | 2017-10-11 | 2023-05-01 | 美商Ｑｐｅｘ生物製藥股份有限公司 | Boronic acid derivatives and synthesis thereof |
| JP7377545B2 (en) | 2017-10-11 | 2023-11-10 | キューペックス バイオファーマ， インコーポレイテッド | Boronic acid derivatives and their synthesis |
| KR102626967B1 (en) * | 2017-10-11 | 2024-01-18 | 큐펙스 바이오파마 인코포레이티드 | Boronic acid derivatives and their synthesis |
| US12016868B2 (en) | 2018-04-20 | 2024-06-25 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
| 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 |
| 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 |
| 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 |
| CN117796401A (en) * | 2023-12-25 | 2024-04-02 | 江苏万隆化学有限公司 | Preparation process of an intermediate antibacterial agent containing 2-hydroxy-6-fluorobenzoic acid methyl ester |
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Application publication date: 20120118 |