JP2552319B2 - 3-amino-2,4,5-trifluorobenzoic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Field of Industrial Application> The present invention relates to a novel 3-amino-2,4,5-trifluorobenzoic acid.

Novel 3-amino-2,4,5 provided by the present invention
Trifluorobenzoic acid is useful as a raw material for polyamides, pharmaceuticals, especially as a starting material in the synthesis of antibacterial agents.

<Prior Art> The 3-amino-2,4,5-trifluorobenzoic acid and the method for producing the same in the present invention have not been reported at all until now.

<Structure of the Invention> As a result of examining the novel method for producing 3-amino-2,4,5-trifluorobenzoic acid, the present inventors found that the compound was 4
It has been found that -amino-3,5,6-trifluorophthalonitrile can be prepared by decarboxylation and hydrolysis in the presence of acid. As the acid, any of the acids used in general hydrolysis reactions such as phosphoric acid, sulfuric acid and mineral acids such as hydrochloric acid can be used, but the use of sulfuric acid is preferred.

 The acid is usually used in the form of an aqueous solution.

Specifically illustrating the production method of the present invention, 4-amino-3,
90 ~ 1 of 5,6-trifluorophthalonitrile in aqueous acid solution
By heating in the temperature range of 70 ° C., novel 3-amino-2,4,5-trifluorobenzoic acid can be produced in high yield by hydrolysis and then decarboxylation reaction.

It is considered that this reaction causes decarboxylation at the same time as hydrolysis as shown in the following formula (A) to generate 3-amino-2,4,5-trifluorobenzoic acid.

The concentration of the aqueous acid solution used in the reaction in the present invention is preferably 20 to 90% by weight, preferably 40 to 70% by weight.
The range of weight% is good. If the acid concentration is high, a rapid reaction is likely to occur, and heat is generated, which is dangerous. If the acid concentration is low,
It is not preferable because the reaction rate decreases and the productivity falls.
Therefore, it is necessary to select an appropriate acid concentration.

The reaction temperature is preferably selected in the temperature range of 90 to 170 ° C, particularly 110 to 150 ° C.

When the reaction temperature is high, it is dangerous because a rapid reaction occurs and an exothermic reaction occurs. When the reaction temperature is low, the reaction rate decreases and the productivity decreases, which is not preferable.

The reaction is preferably carried out under reflux and normal pressure. When the reaction is carried out under reflux, the reaction temperature is particularly controlled by the acid concentration, but the reaction may be carried out under pressure or under reduced pressure so that the temperature is not controlled by the acid temperature. Further, even when it is carried out under normal pressure, it does not necessarily have to be carried out under reflux, and it may be carried out by controlling to a lower temperature.

The reaction time is not particularly limited, but is preferably in the range of 3 to 20 hours.

The concentration of 4-amino-3,5,6-trifluorophthalonitrile charged is preferably 100-1000 parts of the aqueous acid solution with respect to 100 parts of 4-amino-3,5,6-trifluorophthalonitrile. . It is preferable to charge in the range of 200 to 700 parts. The reaction is carried out by simultaneously charging 4-amino-3,5,6-trifluorophthalonitrile and an aqueous acid solution. Further, there are the following methods for controlling the reaction and performing it more safely.

A method of reacting 4-amino-3,5,6-trifluorophthalonitrile by continuously or intermittently adding it to an aqueous acid solution.

A method in which an acid or an aqueous acid solution is continuously or intermittently added to an aqueous slurry of 4-amino-3,5,6-trifluorophthalonitrile to cause a reaction.

4-amino-3,5,6-trifluorophthalonitrile and a low-concentration aqueous acid solution were charged at the same time to start the reaction, and further acid or aqueous acid solution was added continuously or intermittently with the progress of the reaction to obtain the acid concentration. A method of controlling the reaction rate by gradually increasing the reaction temperature by changing the temperature. In that case, the acid concentration charged before the start of the reaction is preferably 10 to 70% by weight, and the acid concentration to be added is preferably 40 to 98% by weight.

The reaction temperature initially starts at 90 to 140 ° C, and the reaction temperature is raised by gradually adding more acid as the reaction progresses.
The reaction is preferably carried out at 120 to 170 ° C.

In any method, an inert organic solvent such as acetone, ketones such as methyl ethyl ketone, nitriles such as acetonitrile, dimethylformamide, and aprotic polar solvent such as sulfolane may be present in the reaction system in any method. good.

Further, the novel substance 3-amino-2,4,5-trifluorobenzoic acid of the present invention is hydrolyzed and decarboxylated at the same time using 4-amino-3,5,6-trifluorophthalonitrile as a starting material. Although it is desirable that the process is simplified because the process is simplified, 4-amino-3,5,6-trifluorophthalonitrile is hydrolyzed in advance to temporarily produce 4-amino-3,5,6-trifluorophthalic acid. It may be produced by decarboxylation reaction. Alternatively, 4-amino-3,5,6-trifluorophthalic acid may be produced by, for example, derivatizing an esterified product such as a methyl ester and then decarboxylation.

4-amino-3,5,6- which is the starting material in the present invention
Trifluorophthalonitrile is a known substance, for example, Ishikawa et al., Journal of Organic Synthetic Chemistry, Vol. 29, No. 8, No.
794 (1971), or Birchall et al., Journal
Of the Chemical Society (Journal of the c
hemical Society (C), Volume 1970, Page 456 (1970)
Year) method can be easily obtained.

Hereinafter, the method for producing a novel substance according to the present invention will be specifically described with reference to Examples, and the analysis results for identifying the obtained novel substance are also shown.

Needless to say, the method for producing 3-amino-2,4,5-trifluorobenzoic acid of the present invention is not limited to the following.

Example 1 A 60% aqueous solution of sulfuric acid 2 was placed in a 4-neck separable flask having a capacity of 200 ml equipped with a stirrer, a thermometer and a Dimroth condenser.
Charge 00g, then charge 4-amino-3,5,6-trifluorophthalonitrile 30.0g (0.152mol) and then raise the temperature,
The mixture was reacted at 128 to 130 ° C. for 3 hours under reflux with sufficient stirring.

Then, after cooling, the reaction solution was poured into ice water, and then 400 mL of an aqueous solution containing 3-amino-2,4,5-trifluorobenzoic acid was added.
3-amino-2,4,5 with ml of isopropyl ether
-Trifluorobenzoic acid was extracted. The obtained isopropyl ether layer was dried over anhydrous magnesium sulfate, and then isopropyl ether was evaporated to dryness to give 3-amino-2,
4,5-Trifluorobenzoic acid 27.7 g (0.145 mol, relative to 4-
Amino-3,5,6-trifluorophthalonitrile yield 95.2
Mol%) was obtained.

Further, this product was purified by recrystallization from a mixed solvent of benzene-ethanol, and the following physical property values were obtained for the purified 3-amino-2,4,5-trifluorobenzoic acid to obtain 3-amino-2 The structure of 4,4,5-trifluorobenzoic acid was determined.

Melting point 140-141 ° C Elemental analysis C (%) H (%) N (%) F (%) Theoretical 43.99 2.11 7.33 29.82 Analytical 44.12 2.13 7.41 29.96 Infrared absorption spectrum (KBr tablet, unit cm ^-1 ) 3420 , 3335 (Amino ν-N-H) 2500-3200 (Hydroxy ν-O-H) 1965 (Carbonyl ν> C = O) (Infrared absorption spectrum is shown in FIG. 1) ¹⁹ F NMR (solvent: acetone -d ⁶ internal standard: CF ₃ COO
H) ppm F ₂ δ −55.87, ddd (J = 19.5,13.4,6.4) F ₄ δ −73.91, ddd (J = 19.5,20.4,8.8) F ₅ δ −67.90, ddd (J = 13.4,20.4,10.7) Example 2 In Example 1, the sulfuric acid concentration was 45% and the reaction temperature was 12
The same procedure as in Example 1 was carried out except that the reaction time was 0 ° C. and the reaction time was 12 hours, and then the same operation was performed.

As a result, 3-amino-2,4,5-trifluorobenzoic acid 2
8.1 g was obtained (relative to 4-amino-3,5,6-trifluorophthalonitrile yield 96.6 mol%).

Example 3 A 60% aqueous solution of sulfuric acid 2 was added to a 4-neck separable flask having a capacity of 200 ml equipped with a stirrer, a thermometer and a Dimroth condenser.
00 g was added, and the mixture was heated with stirring and kept at 130 ° C. To this 4
-Amino-3,5,6-trifluorophthalonitrile 30.0 g
(0.152 mol) was added little by little over 3 hours and the reaction was continued for 2 hours.

Next, the same extraction operation as in Example 1 was carried out, and 27.2 g of 3-amino-2,4,5-trifluorobenzoic acid (0.142 mol, relative to 4-amino-3,5,6-trifluorophthalonitrile yield 9
3.5 mol%) was obtained.

Example 4 76.3 g of water and 30.g (0.152 mol) of 4-amino-3,5,6-trifluorophthalonitrile were charged into a 4-neck separable flask having a capacity of 200 ml equipped with a stirrer, a thermometer and a Dimroth condenser. The mixture was heated under stirring and maintained at 100 ° C. 123.7 g of 97% concentrated sulfuric acid was added dropwise to this over 2 hours at 100 ° C.
To 128 ° C. and further reacted at 128 to 130 ° C. for 3 hours.

Next, the same extraction operation as in Example 1 was performed, and 27.5 g of 3-amino-2,4,5-trifluorobenzoic acid (0.144 mol, relative to 4-amino-3,5,6-trifluorophthalonitrile yield 9
4.5 mol%) was obtained.

Example 5 A 55% sulfuric acid aqueous solution 1 was placed in a 4-neck separable flask having a capacity of 200 ml equipped with a stirrer, a thermometer and a Dimroth condenser.
40 g was added, and then 50 g (0.254 mol) of 4-amino-3,5,6-trifluorophthalonitrile was charged, the temperature was raised, and the reaction was carried out at 128 to 129 ° C. for 7 hours under reflux with sufficient stirring. Thereafter, 9.2 g of 97% by weight concentrated sulfuric acid was gradually added to the reaction solution, and the mixture was reacted under reflux at 131 to 134 ° C for 4 hours in the same manner. 134 ~ 135 ℃
The reaction was completed for 4 hours.

Next, the same extraction operation as in Example 1 was carried out, and 46.8 g (0.246 mol, 3-amino-2,4,5-trifluorobenzoic acid)
The yield was 96.5 mol% based on 4-amino-3,5,6-trifluorophthalonitrile.

[Brief description of drawings]

FIG. 1 is an infrared absorption spectrum diagram of 3-amino-2,4,5-trifluorobenzoic acid obtained in Example 1.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Nobuo Takatani No. 5-8 Nishimitabicho, Suita City, Osaka Prefecture, Central Research Laboratory, Nippon Chemical Chemical Industry Co., Ltd. (56) Reference JP-A-63-88157 (JP, A) )

Claims (1)

(57) [Claims] 1. 3-Amino-2,4,5-trifluorobenzoic acid.