JPH02225438A - Production of 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid - Google Patents
Production of 2,3,5,6-tetrafluoro-4-hydroxybenzoic acidInfo
- Publication number
- JPH02225438A JPH02225438A JP4524089A JP4524089A JPH02225438A JP H02225438 A JPH02225438 A JP H02225438A JP 4524089 A JP4524089 A JP 4524089A JP 4524089 A JP4524089 A JP 4524089A JP H02225438 A JPH02225438 A JP H02225438A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- tetrafluoro
- pentafluorobenzoic
- aqueous solution
- alkali
- Prior art date
- 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.)
- Granted
Links
- FTLHGQOBAPTEHE-UHFFFAOYSA-N 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=C(O)C(F)=C1F FTLHGQOBAPTEHE-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- MEXUTNIFSHFQRG-UHFFFAOYSA-N 6,7,12,13-tetrahydro-5h-indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-one Chemical compound C12=C3C=CC=C[C]3NC2=C2NC3=CC=C[CH]C3=C2C2=C1C(=O)NC2 MEXUTNIFSHFQRG-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000000126 substance Substances 0.000 claims abstract description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 30
- 150000001447 alkali salts Chemical class 0.000 claims abstract description 25
- 239000007864 aqueous solution Substances 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 12
- 239000012736 aqueous medium Substances 0.000 claims abstract description 12
- 238000005805 hydroxylation reaction Methods 0.000 claims abstract description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 8
- 230000002378 acidificating effect Effects 0.000 claims abstract description 6
- 238000010306 acid treatment Methods 0.000 claims description 8
- 238000006386 neutralization reaction Methods 0.000 claims description 7
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 25
- 239000003513 alkali Substances 0.000 abstract description 6
- 239000000243 solution Substances 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 230000000640 hydroxylating effect Effects 0.000 abstract 2
- 230000003472 neutralizing effect Effects 0.000 abstract 2
- 238000006757 chemical reactions by type Methods 0.000 abstract 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 5
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000003916 acid precipitation Methods 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000005187 foaming Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- -1 2,3.5.6-tetrafluoro-4-hydroxybenzoic acid monohydrate Chemical class 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 159000000011 group IA salts Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- QXYLYYZZWZQACI-UHFFFAOYSA-N 2,3,4,5-tetrafluorophenol Chemical compound OC1=CC(F)=C(F)C(F)=C1F QXYLYYZZWZQACI-UHFFFAOYSA-N 0.000 description 1
- BTXKLSXOHABRQQ-UHFFFAOYSA-N 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid;hydrate Chemical compound O.OC(=O)C1=C(F)C(F)=C(O)C(F)=C1F BTXKLSXOHABRQQ-UHFFFAOYSA-N 0.000 description 1
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 101100489867 Mus musculus Got2 gene Proteins 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- UGUYWPVNVFXIAP-UHFFFAOYSA-M potassium;2,3,4,5,6-pentafluorobenzoate Chemical compound [K+].[O-]C(=O)C1=C(F)C(F)=C(F)C(F)=C1F UGUYWPVNVFXIAP-UHFFFAOYSA-M 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、高分子材料、液晶材料、医薬品および農薬の
出発原料として有用な化合物である２、 ３．５．６−
チトラフルオｏ−４−ヒドロキシ安息香酸を、ペンタフ
ルオロ安息香酸を出発原料として用いて、高純度品を安
全かつ工業的に製造する改良された方法に関するもので
ある。[Detailed Description of the Invention] <Industrial Application Field> The present invention provides compounds useful as starting materials for polymeric materials, liquid crystal materials, pharmaceuticals, and agricultural chemicals2, 3.5.6-
The present invention relates to an improved method for safely and industrially producing a highly pure product of titrafluoro-4-hydroxybenzoic acid using pentafluorobenzoic acid as a starting material.
〈従来の技術〉
本発明者らは、ずでに特開昭６０−２０４７４２号で、
ペンタフルオロ安息香酸をアルカリ性物質と水溶液中７
０〜１００℃で反応させ、２．３．５．６−チトラフル
オロー４−とドロキシ安息香酸の塩を生成させ、ついで
生成した２、 ３．５．６−テトラフルオロ−４−ヒド
ロキシ安息香酸塩をＩ）８２〜６の範囲の酸性水溶液に
接触させることを特徴とする２、３゜５．６−テトラフ
ルオロ−４−ヒドロキシ安息香酸の製造方法を提供した
。<Prior art> The present inventors disclosed in Japanese Patent Application Laid-Open No. 60-204742,
Pentafluorobenzoic acid in an aqueous solution with an alkaline substance
The reaction is carried out at 0 to 100°C to produce a salt of 2,3,5,6-titrafluoro-4- and droxybenzoic acid, and then the produced 2,3,5,6-tetrafluoro-4-hydroxybenzoate is I) Provided is a method for producing 2,3°5,6-tetrafluoro-4-hydroxybenzoic acid, which is characterized by contacting with an acidic aqueous solution in the range of 82 to 6.
〈発明が解決しようとする問題点〉
しかし、この方法はその後の検討によると、工業的な大
ロスケールで２．３．５．６−テトラフルオロ−４−ヒ
ドロキシ安息香酸を製造する場合には、以下のような問
題点を有していることが判明した。<Problems to be solved by the invention> However, according to subsequent studies, this method has problems when producing 2.3.5.6-tetrafluoro-4-hydroxybenzoic acid on an industrial large scale. It was found that the following problems were encountered.
すなわち、
■発熱反応の為、反応温度の制御が困難であり、突沸環
条が起こること。That is, (1) Because the reaction is exothermic, it is difficult to control the reaction temperature, and bumping rings occur.
■反応時ホイップクリーム状のスラリーになり、泡立つ
為に容器外に反応物が江溢すること。■During the reaction, it becomes a whipped cream-like slurry and foams, causing the reactants to overflow outside the container.
■反応後に行う酸処理工程において、有毒なフッ化水素
が発生すること。■Toxic hydrogen fluoride is generated during the acid treatment step after the reaction.
である。It is.
そこで、本発明の目的は上記問題点を解消してペンタフ
ルオロ安息香酸から２．３．５．６−テ１−ラフルオロ
ー４−ヒドロキシ安息香酸を高純度で安全かつ工業的に
製造するための改良された方法を提供することにある。SUMMARY OF THE INVENTION Therefore, the purpose of the present invention is to solve the above-mentioned problems and improve the production of 2.3.5.6-te-1-rafluoro-4-hydroxybenzoic acid from pentafluorobenzoic acid in a safe and industrial manner with high purity. The goal is to provide a method for
〈問題点を解決するための手段〉
本発明者らは、上記目的を達成すべく鋭意検討した結果
、
■ペンタフルオロ安息香酸を必要量のアルカリ性物質で
中和反応せしめペンタフルオロ安息香酸のアルカリ塩に
する工程と、ヒドロキシル化の工程を別々にする２段階
の反応型式をとる。<Means for Solving the Problems> As a result of intensive studies to achieve the above object, the present inventors have found that: - Neutralize pentafluorobenzoic acid with a necessary amount of an alkaline substance to form an alkali salt of pentafluorobenzoic acid. A two-step reaction pattern is adopted in which the step of oxidation and the step of hydroxylation are separated.
■ヒドロキシル化反応の際ペンタフルオロ安息香酸のア
ルカリ塩の含有する水媒体中にアルカリ性物質の水溶液
を徐々に滴下する方法を採用する。この２点から反応温
度の制御及び泡立ら現象の１ｌｔｌｌが可能になる。(2) During the hydroxylation reaction, a method is adopted in which an aqueous solution of an alkaline substance is gradually dropped into an aqueous medium containing an alkali salt of pentafluorobenzoic acid. These two points make it possible to control the reaction temperature and control the bubbling phenomenon.
■アルカリ性物質として水酸化ナトリウムおよび／また
は炭酸ナトリウムを用いるのが好ましい。その理由は、
これらを用いることによって生成したフッ化物の大部分
が水に溶解せず、よってあらかじめ濾過等の手法によっ
て反応液からフッ化物を分離できる。よって、反応後に
行う酸処理工程での大間のフッ化水素の発生が防止でき
る。(2) It is preferable to use sodium hydroxide and/or sodium carbonate as the alkaline substance. The reason is,
By using these, most of the fluoride produced is not dissolved in water, and therefore the fluoride can be separated from the reaction solution in advance by a method such as filtration. Therefore, generation of Oma's hydrogen fluoride in the acid treatment step performed after the reaction can be prevented.
以上の知見に基づいて本発明を完成させた。The present invention was completed based on the above findings.
すなわち、本発明はペンタフルオロ安息香酸を出発原料
として２．３．５．６−テトラフルオロー４−ヒドロキ
シ安息香醒を製造するに際し、ω水媒体中においてペン
タフルオロ安息香酸とアルカリ性物質とを反応せしめ、
ペンタフルオロ安息香酸のアルカリ塩を得る中和反応工
程、
（へ）次いで、えられたペンタフルオロ安息香酸のアル
カリ塩を含有する水媒体中にアルカリ性物質の水溶液を
滴下し、７０〜９５℃の温度範囲でペンタフルオロ安Ｑ
香酸のアルカリ塩とアルカリ性物質とを反応ぜしめて２
．３．５．６＝テトラフルオロ−４−ヒドロキシ安息香
酸のアルカリ塩をえるヒト０キモ
（ハ）次いで、えられた２、 ３．５．６−テトラフル
オロ−４−ヒドロキシ安息香酸のアルカリ塩をｐＨ２〜
６の範囲の酸性水溶液に接触させる酸処理工程、
上記のω〜ぐ９の各工程を含むことを特徴とする２、
３．５．６−テトラフルオロ−４−ヒドロキシ安息香酸
の製造方法である。That is, in the present invention, when producing 2.3.5.6-tetrafluoro-4-hydroxybenzoic acid using pentafluorobenzoic acid as a starting material, pentafluorobenzoic acid and an alkaline substance are reacted in an ω aqueous medium. ,
Neutralization reaction step to obtain an alkali salt of pentafluorobenzoic acid, (f) Then, an aqueous solution of an alkaline substance is dropped into an aqueous medium containing the obtained alkali salt of pentafluorobenzoic acid, and the temperature is 70 to 95°C. Pentafluoroan Q in the range
By reacting an alkaline salt of aromatic acid with an alkaline substance, 2
．． 3.5.6=Human zero ability to obtain an alkali salt of tetrafluoro-4-hydroxybenzoic acid (c) Then, the obtained alkali salt of 2,3.5.6-tetrafluoro-4-hydroxybenzoic acid pH2～
2, characterized in that it includes an acid treatment step of contacting with an acidic aqueous solution in the range of 6, and each step of ω to 9 above;
3.5. A method for producing 6-tetrafluoro-4-hydroxybenzoic acid.
以下、本発明の具体的態様を説明する。Hereinafter, specific embodiments of the present invention will be explained.
本発明では第１工程として、水媒体中でペンタフルオロ
安息香酸とアルカリ性物質とからペンタフルオロ安息香
酸のアルカリ塩を生成せしめる中和反応工程を行う。ア
ルカリ性物質としては、水酸化リチウム、水酸化ナトリ
ウム、水酸化カリウム、水酸化セシウムの如くのアルカ
リ金属水酸化物、炭酸ナトリウム、炭酸カリウムの如く
のアルカリ金属炭酸塩等の水溶液中でアルカリ性を示す
ものならばいずれも使用することができる。In the present invention, as a first step, a neutralization reaction step is performed in which an alkali salt of pentafluorobenzoic acid is produced from pentafluorobenzoic acid and an alkaline substance in an aqueous medium. Examples of alkaline substances include those that exhibit alkalinity in aqueous solutions, such as alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, and cesium hydroxide, and alkali metal carbonates such as sodium carbonate and potassium carbonate. If so, you can use either one.
アルカリ性物質の使用量としては、ペンタフルオロ安息
香酸１モル部に対して０．７〜１．３モル部の範囲で加
えるのが好ましい。特に０．９〜１．１モル部の範囲で
加えるのが好ましい。多量に加えた場合発熱反応が著し
くなったり、また泡立ち現象が起こり易くなる。少量の
場合、次工程において発熱反応が著しくなったり、また
泡立ち現象が起こり易くなる。The alkaline substance is preferably used in an amount of 0.7 to 1.3 parts by mole per 1 part by mole of pentafluorobenzoic acid. In particular, it is preferably added in an amount of 0.9 to 1.1 parts by mole. If a large amount is added, the exothermic reaction becomes significant and foaming tends to occur. If the amount is small, the exothermic reaction will be significant in the next step, and foaming will likely occur.
反応温度としては５〜８５℃の範囲が好ましく、特に５
〜４０℃の範囲が好ましい。反応温度が高すぎた場合、
２．３．５．６−テトラフルオロ−４−ヒドロキシ安息
香酸のアルカリ塩が生成し易くなり、次工程で泡立ち現
象が起こり易くなる。従って、できるだ（プ低い温度で
反応を行うのが望ましい。The reaction temperature is preferably in the range of 5 to 85°C, particularly 5 to 85°C.
A range of 40°C to 40°C is preferred. If the reaction temperature is too high,
2.3.5. An alkali salt of 6-tetrafluoro-4-hydroxybenzoic acid is likely to be formed, and a foaming phenomenon is likely to occur in the next step. Therefore, it is desirable to carry out the reaction at a lower temperature.
中和操作を行う際には、ペンタフルオロ安息香酸の含有
する水媒体中に徐々にアルカリ性物質の水溶液を滴下す
るのが好ましい。滴下速度とじてはペンタフルオロ安息
香酸１モル部に対してアルカリ性物質を単位時間当り０
．３〜１．０モル部の範囲、好ましくは０．４〜０．８
モル部の範囲が好ましい。When performing the neutralization operation, it is preferable to gradually drop an aqueous solution of an alkaline substance into an aqueous medium containing pentafluorobenzoic acid. The dropping rate is 0% alkaline substance per mol part of pentafluorobenzoic acid per unit time.
．． In the range of 3 to 1.0 mole parts, preferably 0.4 to 0.8
A range of molar parts is preferred.
次に、本発明では第２工程として、第１工程で得られた
ペンタフルオロ安息香酸のアルカリ塩をアルｈり性物質
と反応せしめて２．３．５．６−テトラフルオロ−４−
ヒドロキシ安息香酸のアルカリ塩を生成せしめるヒドロ
キシ化反応工程を行う。該反応工程で使用するアルカリ
性物質としては、前工程の中和反応工程で使用したもの
と同樟であっＣも異種であってもよい。また、その使用
量は次の反応式に従ってペンタフルオロ安息香酸のアル
カリ塩１モルに対して１．７〜２．５モル倍の範囲、特
に１．９〜２．３モル倍の範囲で加えるのが好ましト
Ｍｅ
（但し、Ｍｅはアルカリ性物質を表わす、）その際、ペ
ンタフルオロ安息香酸のアルカリ塩の水媒体中に、アル
カリ性物質の水溶液を滴下しながら徐々に加えるのが良
い。滴下速度としては、ペンタフルオロ安息香酸のアル
カリ塩１モル部に対してアルカリ性物質を単位時間当り
０．１〜０．６モル部の範囲、特に０．２〜０．４モル
部の範囲で行うのが好ましい。滴下速度が速い場合、反
応温度の制御が困難になり、また泡立ち現象が起こり易
くなる。滴下速度が遅くなると、生産性が悪くなり好ま
しくない。ヒドロキシ化反応工程での反応温度は７０〜
９５℃の範囲が好ましく、特に７５〜９０℃の範囲が好
ましい。反応温度が高い場合、２、３．５．６−チトラ
フルオｏ−４−ヒドロキシ安息香酸のアルカリ塩の異性
体であるテトラフルオロオルソオキシ安息香酸のアルカ
リ塩および脱炭酸反応した形のテトラフルオロフェノー
ルのアルカリ塩が生成しやすくなり、２．３．５．６−
テトラフルオロ−４−ヒドロキシ安息香酸のアルカリ塩
の収率が低下する。反応温度が低い場合、ヒドロキシル
化反応が）＾下速度よりも著しく遅くなる為に、未反応
のアルカリ性物質が蓄積し、ある時点で反応が急激に起
こり、反応制御が困難になる。Next, in the present invention, as a second step, the alkali salt of pentafluorobenzoic acid obtained in the first step is reacted with an alkaline substance to obtain 2.3.5.6-tetrafluoro-4-
A hydroxylation reaction step is carried out to produce an alkali salt of hydroxybenzoic acid. The alkaline substance used in the reaction step may be the same camphor as that used in the neutralization reaction step of the previous step, or C may be a different kind. In addition, the amount used is 1.7 to 2.5 times, particularly 1.9 to 2.3 times by mole per mole of alkali salt of pentafluorobenzoic acid, according to the following reaction formula. (Me represents an alkaline substance) In this case, it is preferable to gradually add an aqueous solution of the alkaline substance dropwise to the aqueous medium of the alkali salt of pentafluorobenzoic acid. The dropping rate is such that the alkaline substance is added per unit time in the range of 0.1 to 0.6 mol parts, particularly in the range of 0.2 to 0.4 mol parts, per 1 mol part of the alkali salt of pentafluorobenzoic acid. is preferable. If the dropping rate is high, it becomes difficult to control the reaction temperature and bubbling phenomenon tends to occur. If the dropping speed is slow, productivity will deteriorate, which is not preferable. The reaction temperature in the hydroxylation reaction step is 70~
A temperature range of 95°C is preferred, and a range of 75 to 90°C is particularly preferred. When the reaction temperature is high, the alkali salt of tetrafluoroorthooxybenzoic acid, which is an isomer of the alkali salt of 2,3.5.6-titrafluoro-4-hydroxybenzoic acid, and the decarboxylated form of tetrafluorophenol are Alkaline salts are easily generated, 2.3.5.6-
The yield of the alkali salt of tetrafluoro-4-hydroxybenzoic acid decreases. When the reaction temperature is low, the hydroxylation reaction is significantly slower than the rate of )^ reduction, so unreacted alkaline substances accumulate, and at a certain point the reaction occurs rapidly, making it difficult to control the reaction.
また、該ヒドロキシル化反応工程でｌＶｊ生ずるフッ化
アルカリは次工程の酸処理工程によって有毒なフッ化水
素を発生するので、ヒドロキシル化反応工程終了後に権
力反応液から除去しておくことが好ましい。本発明者ら
は種々検討した結果、水酸化ナトリウムおよび／または
炭酸ナトリウムを用いて該ヒドロキシル化反応を行い副
生ずる水に難溶性のフッ化ナトリウムを反応液から分離
除去する方法を採用すれば、２．３．５．６−チトラフ
ルオロー４−ヒドロキシ安゛息香酸の製法において全工
程を通して最も有利であることを児い出した。すなわち
、該ヒドロキシル化反応工程で使用するアルカリ性物質
の中で最も高い収率を与えるのｔよ水酸化カリ「クムで
あるが、副生ずるフッ化カリウムは水に対する溶解度が
高いために、フッ化カリウムを除去するのは困難であり
、従って、酸処理工程においてフッ化水素発生対策が必
要となるなど不都合が多い。これに対して、水酸化すｉ
・リウムおよび／または炭酸ナトリウムを使用した場合
、２、３．５．６−テｌ〜ラフルオロ−４−ヒトＯキシ
安息香酸の収率は少々犠牲にされるものの、フッ化水素
発生対策が実質的に不要にるなどの工程および操作２Ｆ
の利点を有する。Further, since the alkali fluoride generated in the hydroxylation reaction step generates toxic hydrogen fluoride in the next acid treatment step, it is preferable to remove it from the power reaction solution after the hydroxylation reaction step is completed. As a result of various studies, the present inventors have found that if a method is adopted in which the hydroxylation reaction is performed using sodium hydroxide and/or sodium carbonate and the by-produced sodium fluoride, which is sparingly soluble in water, is separated and removed from the reaction solution, 2.3.5. The most advantageous process for producing 6-titrafluoro-4-hydroxybenzoic acid was found throughout the entire process. That is, potassium hydroxide gives the highest yield among the alkaline substances used in the hydroxylation reaction process, but potassium fluoride, which is a by-product, has a high solubility in water. It is difficult to remove hydroxide, and therefore there are many inconveniences such as the need to take measures against hydrogen fluoride generation in the acid treatment process.On the other hand, hydroxide
・When using sodium carbonate and/or sodium carbonate, although the yield of 2,3.5.6-tel~lafluoro-4-human O-oxybenzoic acid is slightly sacrificed, it is practically effective as a countermeasure against hydrogen fluoride generation. 2nd floor of processes and operations that are no longer necessary
It has the following advantages.
次に、本発明では第３■稈として、生成した２゜３、５
．６−テトラフルオロ−４−ヒドロキシ安息香酸のアル
カリ塩含有の水溶液にｐＨ２〜６になるように酸性水溶
液を加えて、いわゆる酸析を行い２、３．５．６−チト
ラフルオ０−４−ヒドロキシ安息香酸を生成させる（酸
処理工程）。この際に使用する酸性水溶液を１ｍ製する
ための酸としては、上記のアルカリ塩を中和できるもの
ならばあらゆるものが使用できる。その中でも一般的に
酸析に使用されるｉｕあるいはＭＡ２１が適当である。Next, in the present invention, as the third culm, the generated 2゜3,5
．． An acidic aqueous solution is added to an aqueous solution containing an alkali salt of 6-tetrafluoro-4-hydroxybenzoic acid so that the pH becomes 2 to 6, and so-called acid precipitation is performed to obtain 2,3.5.6-titrafluoro-4-hydroxybenzoic acid. Generate acid (acid treatment step). As the acid for producing 1 m of the acidic aqueous solution used in this case, any acid that can neutralize the above-mentioned alkali salt can be used. Among them, iu or MA21, which is generally used for acid precipitation, is suitable.
酸析後えられた２、 ３．５．６−テトラフルオロ−４
−ヒトＤキシ安息香酸の分離は、抽出溶媒、例えばエー
テル、塩化メチレン、ベンゼン、トルエン等を使って、
２．３．５．６−テトラフルオロ−４−ヒドロキシ安息
香酸を有機層に抽出し分液侵蒸発乾固することによって
行われろ。このようにしてえられた２、 ３．５．６−
テトラフ安息香酸４−ヒドロキシ安息香酸は、白色の高
純度の物質である。2,3.5.6-tetrafluoro-4 obtained after acid precipitation
- Separation of human D-xybenzoic acid using extraction solvents such as ether, methylene chloride, benzene, toluene, etc.
2.3.5. Extract 6-tetrafluoro-4-hydroxybenzoic acid into the organic layer and evaporate to dryness. 2 obtained in this way, 3.5.6-
Tetrafubenzoic acid 4-hydroxybenzoic acid is a white, highly pure substance.
したがって、本発明の方法によってえられる２゜３、５
．６−テトラフルオロ−４−ヒドロキシ安息香酸はこの
ままでも製品となりつるが、さらに再結晶等の方法によ
って緒製して、より高純度の製品としてえることもでき
る。Therefore, the 2°3,5 obtained by the method of the present invention
．． Although 6-tetrafluoro-4-hydroxybenzoic acid can be used as a product as it is, it can also be prepared as a product of higher purity by a method such as recrystallization.
く実 滴 例〉
以下、本発明を実施例によりさらに具体的に説明するが
、本発明はこれらに限定されるものではない。Example> The present invention will be described in more detail below with reference to Examples, but the present invention is not limited thereto.
実施例 １
２０１の釜にペンタフルオロ安息香酸５．０Ｋｙ（２３
，６モル）および水５．０Ｋｇを仕込んだ。そこへ撹拌
下室温に保ちながら３８．５重量％濃度の水酸化ナトリ
ウム水溶液２．４６Ｎ９（水酸化ナトリウム換ｆｉ：２
３．６モル）を定量ポンプを用いて、１．２３Ｎ９／ｈ
ｒの速度で滴下してペンタフルオロ安息香酸ナトリウム
塩を生成させた。その後８５℃に昇温し、同温度を保持
しながら３８．５重陽％濃度の水酸化ナトリウム５．６
５Ｎｙ（水酸化ナトリウム換ｆ’ｉ：５４．２モル）を
定量ポンプを用いて、０．７１にｇ、’ｈｒの速度で滴
下した。Example 1 5.0 Ky of pentafluorobenzoic acid (23
, 6 mol) and 5.0 kg of water were charged. While stirring and keeping at room temperature, add a 38.5% by weight aqueous sodium hydroxide solution 2.46N9 (sodium hydroxide exchange fi: 2
3.6 mol) using a metering pump, 1.23N9/h
The sodium salt of pentafluorobenzoic acid was produced by dropping at a rate of r. After that, the temperature was raised to 85℃, and while maintaining the same temperature, sodium hydroxide with a concentration of 38.5% deuterium was heated to 5.6℃.
Using a metering pump, 5Ny (f'i in terms of sodium hydroxide: 54.2 mol) was added dropwise to 0.71 g, 'hr.
次に、放冷後析出してきた白色のフッ化ツートリウム（
乾燥重量換ｔｉ：９０．１ＧＩ）を炉別し、ついでか液
に対して４４申吊％の硫酸水溶液６．２６ Ｋ９を滴下
して、２．３．５．６−テトラフルオロ−４−ヒドロキ
シ安息香酸をえた。えられた２、 ３．５．６−テトラ
フルオロ−４−ヒドロキシ安息香酸を含む水溶液にイソ
プロピルエーテル２０１を加え、有機層に２．３．５．
６−テトラフルオロ−４−ヒドロキシ安息香酸を抽出し
た。この抽出操作を２回繰り返し、えられたエーテル層
を蒸発乾固して、白色の２、３．５．６−テトラフルオ
ロ−４−ヒドロキシ安息香酸の一水ｊ！！５．２１ｙ（
対ペンタフルオロ安息香酸収率９７．５モル％、純度９
９．３％）をえた。Next, the white fluoride precipitated after being left to cool (
2.3.5.6-tetrafluoro-4-hydroxy I got benzoic acid. Isopropyl ether 201 was added to the obtained aqueous solution containing 2,3.5.6-tetrafluoro-4-hydroxybenzoic acid, and 2.3.5.
6-tetrafluoro-4-hydroxybenzoic acid was extracted. This extraction operation was repeated twice, and the resulting ether layer was evaporated to dryness to give white 2,3.5.6-tetrafluoro-4-hydroxybenzoic acid monohydrate! ! 5.21y(
Yield 97.5 mol% based on pentafluorobenzoic acid, purity 9
9.3%).
実施例 ２
２０Ｊの釜にペンタフルオロ安息香１！１５．０ Ｋｇ
（２３，６モル）および水５．０ Ｋｙを仕込んだ。そ
こへ撹拌上室温に保ちながら３８．５重ω％ａ度の水酸
化カリウム水溶液３．４．４ Ｋｇ（水酸化カリウム換
ｎ：２３．６モル）を定量ポンプを用いて、１．７２／
（ｇ／ｈｒの速度で滴下してペンタフルオロ安息香酸カ
リウム塩を生成させた。その！！８０℃に臂温し、同温
度を保持しながら３８．５重分％濃度の水酸化カリウム
７．９０７（９（水酸化カリウム換算：５４．２モル）
を定量ポンプを用いて、０．７９Ｋｙ／ｈｒの速度で滴
下した。Example 2 1.15.0 kg of pentafluorobenzoin in a 20J pot
(23.6 mol) and 5.0 Ky of water were charged. Thereto, while stirring and keeping at room temperature, 3.4.4 Kg (n: 23.6 mol of potassium hydroxide) of a 38.5 wt ω% a degree potassium hydroxide aqueous solution was added using a metering pump, and 1.72/
Potassium pentafluorobenzoate salt was produced by dropping at a rate of (g/hr). Potassium hydroxide with a concentration of 38.5% by weight was heated to 80°C and maintained at the same temperature.7. 907 (9 (potassium hydroxide equivalent: 54.2 mol)
was added dropwise using a metering pump at a rate of 0.79 Ky/hr.
次に、放冷後４４重怨％のＦＡＲ水溶液６．２６ Ｋｇ
を滴下して、２．３．５．６−チトラフルオロー４−と
ドロキシ安息香酸をえた。えられた２、 ３．５．６−
チトラフルオロー４−ヒドロキシ安息香酸を含む水溶液
にイソプロピルエーテル２０４を加え、有機層に２．３
．５．６−チトラフルオロー４−とドロキシ安息香酸を
抽出した。この抽出操作を２回繰り返し、えられたエー
テル層を蒸発乾固して、白色の２、３．５．６−テトラ
フルオロ−４−ヒドロキシ安息香酸の一水塩５．３０Ｋ
ｇ（対ペンタフルオロ安息香酸収率９８．４モル％４純
度９８．５％）をえた。Next, after cooling, 6.26 kg of 44% FAR aqueous solution was added.
was added dropwise to obtain 2.3.5.6-titrafluoro-4- and droxybenzoic acid. Got 2, 3.5.6-
Isopropyl ether 204 was added to an aqueous solution containing titrafluoro-4-hydroxybenzoic acid, and 2.3
．． 5.6-Titrafluoro-4- and droxybenzoic acid were extracted. This extraction operation was repeated twice, and the resulting ether layer was evaporated to dryness to yield 5.30K of white 2,3.5.6-tetrafluoro-4-hydroxybenzoic acid monohydrate.
g (yield 98.4 mol% based on pentafluorobenzoic acid, purity 98.5%) was obtained.
Claims (1)
５，６−テトラフルオロ−４−ヒドロキシ安息香酸を製
造するに際し、 （イ）水媒体中においてペンタフルオロ安息香酸とアル
カリ性物質とを反応せしめペンタフ ルオロ安息香酸のアルカリ塩を得る中和反 応工程、 （ロ）次いで得られたペンタフルオロ安息香酸のアルカ
リ塩を含有する水媒体中にアルカリ 性物質の水溶液を滴下し、７０〜９５℃の 温度範囲でペンタフルオロ安息香酸のアル カリ塩とアルカリ性物質とを反応せしめて ２，３，５，６−テトラフルオロ−４−ヒドロキシ安息
香酸のアルカリ塩を得るヒドロキシル化反応工程、 （ハ）次いで、えられた２，３，５，６−テトラフルオ
ロ−４−ヒドロキシ安息香酸のアルカリ塩 をｐＨ２〜６の範囲の酸性水溶液に接触さ せる酸処理工程、 上記（イ）〜（ハ）の各工程を含むことを特徴とする２
，３，５，６−テトラフルオロ−４−ヒドロキシ安息香
酸の製造方法。 ２、中和反応工程（イ）において、５〜４０℃の温度範
囲でペンタフルオロ安息香酸を含有する水媒体中にアル
カリ性物質の水溶液を滴下することを特徴とする請求項
１記載の方法。 ３、アルカリ性物質がアルカリ金属水酸化物および／ま
たはアルカリ金属炭酸塩であることを特徴とする請求項
１記載の方法。 ４、アルカリ性物質が水酸化ナトリウムおよび／または
炭酸ナトリウムであることを特徴とする請求項３記載の
方法。 ５、請求項４記載の方法において、ヒドロキシル化反応
工程（ロ）後、副生するフッ化ナトリウムを分離除去し
、次いで酸処理工程（ハ）を行なうことを特徴する２，
３，５，６−テトラフルオロ−４−ヒドロキシ安息香酸
の製造方法。 ６、中和反応工程（イ）において、５〜４０℃の温度範
囲でペンタフルオロ安息香酸を含有する水媒体中に水酸
化ナトリウムおよび／または炭酸ナトリウムの水溶液を
滴下することを特徴とする請求項５記載の方法。[Claims] 1. Using pentafluorobenzoic acid as a starting material, 2.3.
When producing 5,6-tetrafluoro-4-hydroxybenzoic acid, (a) a neutralization reaction step of reacting pentafluorobenzoic acid with an alkaline substance in an aqueous medium to obtain an alkali salt of pentafluorobenzoic acid; b) Next, an aqueous solution of an alkaline substance is dropped into the aqueous medium containing the obtained alkali salt of pentafluorobenzoic acid, and the alkali salt of pentafluorobenzoic acid and the alkaline substance are reacted at a temperature range of 70 to 95°C. a hydroxylation reaction step to obtain an alkali salt of 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid; (c) then the obtained 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid; Acid treatment step of contacting an alkali salt of an acid with an acidic aqueous solution having a pH range of 2 to 6, characterized in that it includes each of the steps (a) to (c) above.
, 3,5,6-tetrafluoro-4-hydroxybenzoic acid production method. 2. The method according to claim 1, wherein in the neutralization reaction step (a), the aqueous solution of the alkaline substance is dropped into the aqueous medium containing pentafluorobenzoic acid at a temperature range of 5 to 40°C. 3. The method according to claim 1, wherein the alkaline substance is an alkali metal hydroxide and/or an alkali metal carbonate. 4. The method according to claim 3, wherein the alkaline substance is sodium hydroxide and/or sodium carbonate. 5. The method according to claim 4, characterized in that after the hydroxylation reaction step (b), by-produced sodium fluoride is separated and removed, and then the acid treatment step (c) is performed.
A method for producing 3,5,6-tetrafluoro-4-hydroxybenzoic acid. 6. A claim characterized in that in the neutralization reaction step (a), an aqueous solution of sodium hydroxide and/or sodium carbonate is dropped into an aqueous medium containing pentafluorobenzoic acid at a temperature range of 5 to 40°C. 5. The method described in 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1045240A JPH0662498B2 (en) | 1989-02-28 | 1989-02-28 | Method for producing 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1045240A JPH0662498B2 (en) | 1989-02-28 | 1989-02-28 | Method for producing 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02225438A true JPH02225438A (en) | 1990-09-07 |
| JPH0662498B2 JPH0662498B2 (en) | 1994-08-17 |
Family
ID=12713729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1045240A Expired - Fee Related JPH0662498B2 (en) | 1989-02-28 | 1989-02-28 | Method for producing 2,3,5,6-tetrafluoro-4-hydroxybenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0662498B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5446198A (en) * | 1992-12-17 | 1995-08-29 | Hoechst Aktiengesellschaft | 4-hydroxy-2,3,5-trifluorobenzoic acid and a process for its preparation |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022061045A1 (en) | 2020-09-16 | 2022-03-24 | Ceres Greenhouse Solutions Llc | Multi-source heat exchange system employing a ground-energy storage system for controlled environment enclosures |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60204742A (en) * | 1984-03-30 | 1985-10-16 | Nippon Shokubai Kagaku Kogyo Co Ltd | Preparation of tetrafluoro-4-hydroxybenzoic acid |
-
1989
- 1989-02-28 JP JP1045240A patent/JPH0662498B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60204742A (en) * | 1984-03-30 | 1985-10-16 | Nippon Shokubai Kagaku Kogyo Co Ltd | Preparation of tetrafluoro-4-hydroxybenzoic acid |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5446198A (en) * | 1992-12-17 | 1995-08-29 | Hoechst Aktiengesellschaft | 4-hydroxy-2,3,5-trifluorobenzoic acid and a process for its preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0662498B2 (en) | 1994-08-17 |
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