JPS62108839A - Production of 3-fluorobenzoic acid compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for pharmaceuticals and raw material of liquid crystal, easily in high yield and purity with a simple reaction apparatus, by using a 3-fluorobenzotrifluoride compound as a raw material, reacting with an inexpensive acid under normal pressure and reacting with water. CONSTITUTION:The objective compound can be produced by reacting 1mol of a 3-fluorobenzotrifluoride compound of formula I (X, Y and Z are H, Cl, F or Br) with 1-10mol of an acid such as concentrated sulfuric acid under autogeneous pressure or externally applied pressure at 80-200 deg.C for <=6hr in liquid phase and reacting 1mol of the resultant esterified compound with 1-50mol of water preferably in liquid phase under normal temperature and pressure condition for <=2hr. It is important to keep the water-content of the acid to <=50wt%. EFFECT:The objective compound can be easily separated from the raw material and the acid and can be produced in high purity without using complicate procedures such as recrystallization.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 3-fluorobenzoic acids useful as intermediates for pharmaceuticals and raw materials for liquid crystals.

[Prior art] A method for producing 3-fluorobenzoic acids is disclosed in Japanese Patent Application Laid-Open No. 58-74.
667 and Japanese Unexamined Patent Publication No. 58-15-0543 are known. According to JP-A-58-74667, a method for producing 2,4-dichloro-5-fluorobenzoic acid, ρ-aroic acid, is disclosed according to the following reaction route.

Furthermore, JP-A-58-150543 discloses a method for producing 2,4.5-trifluorobenzoic acid according to the following reaction route.

[Problems to be solved by the invention] In the method of JP-A-58-74667, HF, which is highly dangerous in reaction operation, must be used at a high temperature of 130 to 140°C, and 2.4% of the starting material -Dichloro-5-methylaniline has a problem in that it is not easily available. Furthermore, production of difluoro and trifluorobenzoic acids is even more difficult.

In the method of JP-A-58-150543.

Problems include the use of the Grignard reaction, which is flammable and not easy to industrialize, and the use of 2,4.5-trifluorobromobenzene, a raw material that is not easy to obtain.

[L-stage for solving the problems] The present invention solves the difficulty of raw material input, which the prior art had.
It was developed to solve the disadvantages of using Grignard reaction and the dangers of using HF at high temperatures, and it is a reaction between 3-fluorobenz trifluoride represented by general formula (I) of F and an acid. The present invention relates to a method for producing 3-fluorobenzoic acids, which is characterized in that 3-fluorobenzoic acids represented by the general formula (ir) are obtained by allowing the 3-fluorobenzoic acids to react with water.

(where x, y, z are H, CI, F, or B, respectively)
r) The starting materials 3-fluorobenzotrifluoride include p-chlorobenzotrifluoride, 2,4.5-trifluorobenzotrifluorite, 3,4-dichlorobenzotrifluoride, and 2.
It can be synthesized using 4-dichlorobencytrifluoride or the like. For example, 3-fluorobensitrifluorides can be easily obtained by the following reaction.

The reaction between 3-fluorobensitrifluoride and an acid is a liquid phase reaction under autogenous pressure or under pressure. The reaction temperature is 80 to 200°C, preferably 100 to 150°C.
It is best to choose from the range. It is thought that an esterified product is produced by the reaction of the trifluoromethyl group of 3-fluorohair citrifluoride with an acid, but it is important that this esterified product exists stably. Therefore,
Preferred acids are selected from those that yield stable esterification products, and sulfuric acid, phosphoric acid, 9 fuming sulfuric acid, and the like are particularly preferred. As fuming sulfuric acid, the concentration of trioxide contained is 1 to 1
It is preferable to use a liquid containing 0% by weight at room temperature, and a substance with a high trioxide content is not preferable because sulfonation tends to occur. Anhydrous acids are particularly preferred because they have high reactivity with 3-fluorobensitrifluorides, and the reactivity decreases as the wood content increases. It is important that the F content is preferably 20% by weight or less.

The amount of acid used is 1 to 10 times the mole of 3-fluorobensitrifluoride as the starting material, preferably 3 to 6 times.
A double molar ratio is appropriate; if the amount of acid is too small, the reaction will not proceed sufficiently, and acid waste liquid will increase in a colander during post-treatment, which is not preferable. Since HF is generated in addition to the esterified product as a reaction product, the reactor material is preferably made of Hastelloy or Inconel.The zero reaction in which HF is absorbed and separated in an alkaline aqueous solution such as KOH takes about 6 hours or less, and the reaction conditions are In some cases, it can be completed within 3 hours.

The reaction between the esterified product obtained by the reaction with the acid and the wood is preferably carried out in a liquid phase. The reaction temperature is O'C to 100C5, preferably θC to 30C. The appropriate amount of water to be used is 1 to 50 times the mole of the esterified product, preferably 3 to 20 times the mole.
After washing with water and drying, the reaction in which the desired 3-fluorobenzoic acids can be obtained is usually completed within about 2 hours, and depending on the reaction conditions, within about 10 minutes.

Example 1 2,4-dichloro- on a 200 Q Hastelloy C reaction base
40 g of 5-fluorobenzotrifluoride and concentrated sulfuric acid (9
6z sulfuric acid) 40gti: Preparation, 100℃ to 140℃
The IF generated after reacting for about 3 hours at a reaction temperature of KO
After cooling the 0 reaction solution absorbed in H aqueous solution, about 500cc
The mixture was poured into water ice and reacted for 1 hour, and the resulting solid was filtered, washed with water, and dried.

The obtained solid was subjected to 19F-NMR, 1H-NMR, J
As a result of analysis using R, it was found to be 2,4-cyclo-5-fluoroamine Q, 6m. Yield after drying is 3
It was 3.8g.

Examples 2 to 7 Various 3-fluorobennes under the same conditions as Example 1]
-Reacted refluorides to obtain the corresponding 3-fluoroamyl Ω and aromatic acids. The results are shown in Table 1. The yield is the yield of 3-fluoroamic acid compounds based on the raw materials.

Example 8 A reaction was carried out under the same conditions as in Example 1 except that concentrated sulfuric acid was replaced with 80% sulfuric acid, and 2-chloro-4,5-difluorobenzoic acid was produced from 2-chloro-4,5-difluorobenzotrifluoride. Obtained with a yield of 38%.

Example 9 30 g of 2,4-dichloro-5-fluorobenzotrifluoride and 83 g of 80% sulfuric acid were reacted in a 200 m(2) Hastelloy C reactor at 120 to 135° C. for about 6 hours.

Thereafter, the reaction solution was poured into ice water and allowed to react for 1 hour. The product was extracted with methylene chloride and analyzed by gas chromatography, and the reaction rate of the raw materials was 48%. Recrystallization was performed from this methylene chloride solution to obtain 10 g of the desired 2,4-dichloro-5-fluorobenzoic acid.

[Effects of the Invention] In the present invention, 3-fluorobenzoic acids can be easily obtained from 3-fluorobenzotrifluorides in high yields, and the structure of the raw materials has little influence on the reaction yield. The acid used for this is also cheap. Furthermore, since the reaction can generally be carried out at normal pressure, the reaction apparatus is simple. Furthermore, since it is easy to separate raw materials and LI-like substances or acids and 1-1 substances,
A highly pure target compound can be obtained without using complicated purification steps such as recrystallization.

Hand-completed City Paperback December 10, 1985 El 4 ￥ Authorized Office Commissioner's Palace 1. 13 Displays 1985 Patent Application No. 248995 62, Title of Invention 3 - Process for Producing Fluorobenzoic Acids 3, Amendment Relationship with the case of a person who does
(OO4) Asahi Glass Co., Ltd. Toranomon Chiyoda Building Voluntary amendment 6, Number of inventions increased by amendment None 8, Contents of amendment I (2) Lines 9 from page 4 of the specification] "...3-
"Fluoro mouth..." is corrected to "...3-Fluoro...".

Shil I ■――

Claims (1)

[Claims] 1. 3-fluorobenzotrifluorides represented by the following general formula (I) are reacted with an acid, and then reacted with water to produce 3-fluorobenzotrifluorides represented by the following general formula (II). - A method for producing 3-fluorobenzoic acids, which comprises obtaining fluorobenzoic acids. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formulas, X, Y, and Z are H, Cl, F, or Br, respectively)
)