JPH0610158B2 - Method for producing 3-fluorobenzoic acids - Google Patents
Method for producing 3-fluorobenzoic acidsInfo
- Publication number
- JPH0610158B2 JPH0610158B2 JP60248995A JP24899585A JPH0610158B2 JP H0610158 B2 JPH0610158 B2 JP H0610158B2 JP 60248995 A JP60248995 A JP 60248995A JP 24899585 A JP24899585 A JP 24899585A JP H0610158 B2 JPH0610158 B2 JP H0610158B2
- Authority
- JP
- Japan
- Prior art keywords
- reaction
- acid
- producing
- fluorobenzoic
- fluorobenzotrifluorides
- 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.)
- Expired - Lifetime
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、医薬品の中間体や液晶の原料として有用なる
３−フルオロ安息香酸類の製造方法に関するものであ
る。TECHNICAL FIELD The present invention relates to a method for producing 3-fluorobenzoic acids, which is useful as an intermediate for pharmaceuticals and a raw material for liquid crystals.
［従来の技術］ ３−フルオロ安息香酸類の製法には、特開昭５８−７４
６６７や特開昭５８−１５０５４３に示される方法が知
られている。特開昭５８−７４６６７によれば、下記反
応経路に従つて、2,4-ジクロロ-5-フルオロ安息香酸を
製造する方法が示されている。[Prior Art] A method for producing 3-fluorobenzoic acids is described in JP-A-58-74.
667 and the method disclosed in JP-A-58-150543 are known. Japanese Unexamined Patent Publication No. 58-74667 discloses a method for producing 2,4-dichloro-5-fluorobenzoic acid according to the following reaction route.
又、特開昭５８−１５０５４３によれば、下記反応経路
に従つて、2,4,5-トリフルオロ安息香酸を製造する方法
が示されている。 Further, JP-A-58-150543 discloses a method for producing 2,4,5-trifluorobenzoic acid according to the following reaction route.
［発明の解決しようとする問題点］ 特開昭５８−７４６６７の方法においては、反応操作上
危険性の高いＨＦを130〜140℃の高温で使用せざるを得
ず、出発原料の2,4-ジクロロ-5-メチルアニリンは入手
が容易でないという問題点がある。又、ジフルオロやト
リフルオロ安息香酸類の製造は、さらに困難である。特
開昭５８−１５０５４３の方法においては、可燃性で工
業化が容易でないグリニャール反応を用いる点、及び入
手が容易でない原料2,4,5-トリフルオロブロモベンゼン
を用いる点が問題である。 [Problems to be Solved by the Invention] In the method of JP-A-58-74667, HF, which has a high risk in reaction operation, must be used at a high temperature of 130 to 140 ° C. -Dichloro-5-methylaniline has a problem that it is not easily available. Further, the production of difluoro or trifluorobenzoic acids is more difficult. The method of JP-A-58-150543 is problematic in that it uses a Grignard reaction that is flammable and is not easily industrialized, and that the raw material 2,4,5-trifluorobromobenzene is not easily available.
［問題点を解決するための手段］ 本発明は、従来技術が有していた、原料入手の困難性、
グリニャール反応を用いたり、ＨＦを高温で使用するこ
とによる危険性といつた欠点を解決すべくなされたもの
であり、下記一般式（Ｉ）で表わされる３−フルオロベ
ンゾトリフルオライド類と酸とを反応せしめた後、水と
反応せしめることにより、下記一般式（II）で表わされ
る３−フルオロ安息香酸類を得ることを特徴とする３−
フルオロ安息香酸類の製造方法に関するものである。[Means for Solving Problems] The present invention has the difficulty of obtaining raw materials, which the conventional technology has,
The purpose of the present invention is to solve the dangers and drawbacks caused by using the Grignard reaction or using HF at high temperature. The 3-fluorobenzotrifluorides represented by the following general formula (I) and an acid are After reacting, it is reacted with water to obtain 3-fluorobenzoic acid represented by the following general formula (II).
The present invention relates to a method for producing fluorobenzoic acids.
（式中、X,Y,ZはそれぞれH,Cl,F,又はBr）出発原料の３
−フルオロベンゾトリフルオライド類は、入手容易で安
価なp-クロルベンゾトリフルオライド，2,4,5-トリフル
オロベンゾトリフルオライド，3,4-ジクロロベンゾトリ
フルオライド，2,4-ジクロロベンゾトリフルオライド等
を用いて合成可能である。例えば、以下の反応により容
易に３−フルオロベンゾトリフルオライド類を得ること
ができる。 (In the formula, X, Y, and Z are H, Cl, F, or Br, respectively) 3 of the starting material
-Fluorobenzotrifluorides include p-chlorobenzotrifluoride, 2,4,5-trifluorobenzotrifluoride, 3,4-dichlorobenzotrifluoride and 2,4-dichlorobenzotrifluoride, which are easily available and inexpensive. Can be synthesized using. For example, 3-fluorobenzotrifluorides can be easily obtained by the following reaction.
３−フルオロベンゾトリフルオライド類と酸との反応
は、自圧又は加圧下の液相反応が好ましい。反応温度
は、80〜200℃、好ましくは100〜150℃の範囲から選択
すると良い。３−フルオロベンゾトリフルオライド類の
トリフルオロメチル基と酸との反応により、エステル化
物が生成すると考えられるが、このエステル化物が安定
に存在することが重要である。従つて、好ましい酸とし
ては、安定なエステル化物を与えるものから選択され、
硫酸，リン酸，発煙硫酸等が特に好ましい。発煙硫酸と
しては、含有三酸化イオウ濃度が１〜10重量％の常温で
液体のものが好ましく、三酸化イオウ含有率の高いもの
は、スルホン化が起こりやすいため好ましくない。無水
の酸が３−フルオロベンゾトリフルオライド類との反応
性が高いため特に好ましく、水の含有量が増加するに従
つて反応性が低下するため、酸中の水の含有量を少なく
とも50重量％以下、好ましくは20重量％以下とすること
が重要である。 The reaction between 3-fluorobenzotrifluorides and an acid is preferably a liquid phase reaction under self-pressure or under pressure. The reaction temperature may be selected from the range of 80 to 200 ° C, preferably 100 to 150 ° C. It is considered that an esterified product is produced by the reaction of the trifluoromethyl group of 3-fluorobenzotrifluorides with an acid, but it is important that this esterified product is stably present. Therefore, the preferred acid is selected from those which give stable esterification products,
Sulfuric acid, phosphoric acid, fuming sulfuric acid and the like are particularly preferable. As fuming sulfuric acid, those containing sulfur trioxide at a concentration of 1 to 10% by weight and liquid at room temperature are preferable, and those having a high sulfur trioxide content are not preferable because sulfonation easily occurs. The anhydrous acid is particularly preferable because it has high reactivity with 3-fluorobenzotrifluorides, and the reactivity decreases as the content of water increases, so that the content of water in the acid is at least 50% by weight. It is important to set the content below, preferably 20% by weight or less.
酸の使用量は、出発原料の３−フルオロベンゾトリフル
オライド類に対して１〜10倍モル、好ましくは３〜６倍
モルが適当であり、酸の量が少なすぎると、反応が充分
に進行せず、又多すぎると後処理時の配廃液量が増える
ため好ましくない。反応生成物としてエステル化物の
他、ＨＦが発生するため、反応器材質はハステロイやイ
ンコネル製が好ましく、ＨＦはＫＯＨ等のアルカリ水溶
液に吸収し分離する。反応はは、およそ６時間以内で、
反応条件によつてはおよそ３時間以内で完結する。The amount of the acid used is appropriately 1 to 10 times mol, preferably 3 to 6 times mol, of the starting 3-fluorobenzotrifluorides. If the amount of the acid is too small, the reaction proceeds sufficiently. If it is not added, or is too large, the amount of waste liquid to be distributed during post-treatment increases, which is not preferable. Since HF is generated as a reaction product in addition to an esterified product, the material of the reactor is preferably made of Hastelloy or Inconel, and HF is absorbed by an alkaline aqueous solution such as KOH and separated. The reaction is within about 6 hours,
Depending on the reaction conditions, it will be completed within about 3 hours.
酸との反応で得られるエステル化物と水との反応は、液
相が好ましい。反応温度は０℃〜100℃、好ましくは０
℃〜30℃である。水の使用量は、エステル化物に対して
１〜50倍モル、好ましくは３〜20倍モルが適当である。
反応は常温常圧で容易に進行し、ろ過、水洗後、乾燥し
て目的とする３−フルオロ安息香酸類を得ることができ
る。反応は、通常約２時間以内で、反応条件によつては
約10分以内で完結する。The reaction between the esterified product obtained by the reaction with an acid and water is preferably in the liquid phase. The reaction temperature is 0 ° C to 100 ° C, preferably 0 ° C.
It is ℃ ~ 30 ℃. The amount of water used is 1 to 50 times mol, preferably 3 to 20 times mol, of the esterified product.
The reaction easily proceeds at room temperature and atmospheric pressure, and after filtration, washing with water, and drying, the desired 3-fluorobenzoic acids can be obtained. The reaction is usually completed within about 2 hours, and within about 10 minutes depending on the reaction conditions.
実施例１ 200mlハステロイＣ製反応器に2,4-ジクロロ-5-フルオロ
ベンゾトリフルオリド40ｇと濃硫酸（96%硫酸）40gを仕
込み、100℃から140℃の反応温度で約３時間反応させ
た。発生するＨＦはＫＯＨ水溶液に吸収させた。反応液
を冷却後、約500ccの氷水に投入し、１時間反応させ、
生成する固体をろ過、水洗後、乾燥した。得られた固体
を19F-NMR,1H-NMR,IRで分析した結果、2,4-ジクロロ-5-
フルオロ安息香酸であることがわかつた。乾燥後の収量
は33.8ｇであった。Example 1 A 200 ml Hastelloy C reactor was charged with 40 g of 2,4-dichloro-5-fluorobenzotrifluoride and 40 g of concentrated sulfuric acid (96% sulfuric acid) and reacted at a reaction temperature of 100 to 140 ° C. for about 3 hours. . The generated HF was absorbed in a KOH aqueous solution. After cooling the reaction solution, add it to about 500cc of ice water and let it react for 1 hour.
The produced solid was filtered, washed with water, and then dried. The obtained solid was analyzed by 19 F-NMR, 1 H-NMR, and IR, and it was found that 2,4-dichloro-5-
It was found to be fluorobenzoic acid. The yield after drying was 33.8 g.
実施例２〜７ 実施例１と同様の条件で、種々の３−フルオロベンゾト
リフルオリド類を反応させ、対応する３−フルオロ安息
香酸類を得た。結果を表１に示す。収率は、原料に対す
る３−フルオロ安息香酸類の収率である。Examples 2 to 7 Various 3-fluorobenzotrifluorides were reacted under the same conditions as in Example 1 to obtain corresponding 3-fluorobenzoic acids. The results are shown in Table 1. The yield is the yield of 3-fluorobenzoic acids based on the raw materials.
実施例８ 濃硫酸を80％硫酸に代えた以外、実施例１と同様の条件
で反応させ、2-クロロ-4,5-ジフルオロベンゾトリフル
オリドから2-クロロ-4,5-ジフルオロ安息香酸を収率38
％で得た。 Example 8 2-chloro-4,5-difluorobenzoic acid was converted from 2-chloro-4,5-difluorobenzotrifluoride by reacting under the same conditions as in Example 1 except that concentrated sulfuric acid was changed to 80% sulfuric acid. Yield 38
Earned in%.
実施例９ 200mlハステロイＣ製反応器に2,4-ジクロロ-5-フルオロ
ベンゾトリフルオリド30ｇと80％硫酸63ｇを、120〜135
℃で約６時間反応させた。その後、反応液を氷水に投入
し、１時間反応させ生成物を塩化メチレンで抽出し、ガ
スクロマトグラフィーで分析した処、原料の反応率は46
％であった。この塩化メチレン溶液から再結晶し、目的
とする2,4-ジクロロ-5-フルオロ安息香酸10ｇを得た。Example 9 In a 200 ml Hastelloy C reactor, 2,4-dichloro-5-fluorobenzotrifluoride (30 g) and 80% sulfuric acid (63 g) were added to 120-135.
The reaction was carried out at ℃ for about 6 hours. Then, the reaction solution was poured into ice water, reacted for 1 hour, the product was extracted with methylene chloride and analyzed by gas chromatography.
%Met. Recrystallization from this methylene chloride solution gave 10 g of the desired 2,4-dichloro-5-fluorobenzoic acid.
［発明の効果］ 本発明では、３−フルオロ安息香酸類を３−フルオロベ
ンゾトリフルオリド類から容易に高収率で得ることがで
き、反応収率への原料の構造の影響も小さい。又、反応
に用いる酸も安価である。又、反応は一般に常圧で行な
えることより、反応装置が簡単である。さらに、原料と
目的物あるいは酸と目的物の分離が容易なため、高純度
の目的化合物を再結晶等の複雑な精製工程を用いること
なしに得ることができる。[Effect of the Invention] In the present invention, 3-fluorobenzoic acids can be easily obtained from 3-fluorobenzotrifluorides in a high yield, and the influence of the structure of the raw material on the reaction yield is small. The acid used for the reaction is also inexpensive. Further, the reaction can be generally carried out at atmospheric pressure, and thus the reaction apparatus is simple. Furthermore, since the raw material and the target substance or the acid and the target substance can be easily separated, a highly pure target compound can be obtained without using a complicated purification step such as recrystallization.
Claims (1)
ロベンゾトリフルオライド類と酸とを反応せしめた後、
水と反応せしめることにより、下記一般式（II）で表わ
される３−フルオロ安息香酸類を得ることを特徴とする
３−フルオロ安息香酸類の製造方法。 （式中、X,Y,ZはそれぞれH,Cl,F,又はBr）1. After reacting 3-fluorobenzotrifluorides represented by the following general formula (I) with an acid,
A method for producing 3-fluorobenzoic acid, which comprises reacting with water to obtain 3-fluorobenzoic acid represented by the following general formula (II). (In the formula, X, Y, and Z are H, Cl, F, or Br, respectively)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60248995A JPH0610158B2 (en) | 1985-11-08 | 1985-11-08 | Method for producing 3-fluorobenzoic acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60248995A JPH0610158B2 (en) | 1985-11-08 | 1985-11-08 | Method for producing 3-fluorobenzoic acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62108839A JPS62108839A (en) | 1987-05-20 |
| JPH0610158B2 true JPH0610158B2 (en) | 1994-02-09 |
Family
ID=17186445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60248995A Expired - Lifetime JPH0610158B2 (en) | 1985-11-08 | 1985-11-08 | Method for producing 3-fluorobenzoic acids |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0610158B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0342849A3 (en) * | 1988-05-19 | 1990-03-14 | Pfizer Inc. | Intermediates for preparing 1,4-dihydro-4-oxo-quinoline-3-carboxylic acid esters |
| JPH02215744A (en) * | 1989-02-15 | 1990-08-28 | Sds Biotech Kk | Benzoic acid derivative and production thereof |
| CN100357245C (en) * | 2004-08-26 | 2007-12-26 | 大连绿源药业有限责任公司 | Prepn process of 2,5-dihalogeno benzoic acid |
| CN1328238C (en) * | 2004-09-06 | 2007-07-25 | 大连绿源药业有限责任公司 | Preparation of 2,4,5-trifluo-benzoic acid |
| CN110357773A (en) * | 2019-07-08 | 2019-10-22 | 南通嘉禾化工有限公司 | The synthesis of 3- chloro-4-hydroxyl benzoic acid |
| CN114790134A (en) * | 2021-01-26 | 2022-07-26 | 江苏中旗科技股份有限公司 | Method for synthesizing 2-chloro-4-fluorobenzoic acid through Meerwein arylation reaction |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3165721D1 (en) * | 1980-02-05 | 1984-10-04 | Ici Plc | Method of preparing fluorine-substituted diphenyl ether derivatives and fluorine-substituted halogeno benzene derivatives for use therein |
| DE3142856A1 (en) * | 1981-10-29 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING 2,4-DICHLOR-5-FLUOR-BENZOYL CHLORIDE |
-
1985
- 1985-11-08 JP JP60248995A patent/JPH0610158B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62108839A (en) | 1987-05-20 |
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