JPH0316342B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to 2,3,5,6-tetrafluoro-4- which is a compound useful as a starting material for the synthesis of polymeric materials, liquid crystal materials, pharmaceuticals and agricultural chemicals. This invention relates to a method for producing mercaptobenzoic acid.

Prior Art Methods for synthesizing 2,3,5,6-tetrafluoro-4-mercaptobenzoic acid include, for example, US Pat. No. 3,459,794 and GM Brooke et al. J. Chem.
Soc.(C), 1967, p. 865. According to the method described in U.S. Pat. No. 3,459,794, 2,3.5,6-tetrafluorobenzoic acid and n-butyllithium are reacted at -65°C in anhydrous tetrahydrofuran, and then sulfur is introduced into the aromatic ring using elemental sulfur. By subsequent acid precipitation, the desired product was obtained with a yield of 68.7%. Also, J.Chem.Soc.
(C) According to the method described on page 865 of 1967, 2,3,5,6-tetrafluorothiophenol and n-butyllithium are reacted at -67°C in anhydrous tetrahydrofuran, and then aromatized with carbon dioxide gas. By introducing a carboxyl group into the ring and subsequent acid precipitation, the desired product was obtained in a crude yield of 73%.

Since all of these methods use n-butyllithium as a reaction reagent, severe reaction conditions such as anhydrification of the solvent and low-temperature reaction are unavoidable. Moreover, in both methods, the starting materials are not only very expensive, but also the yield of the desired product is not high, making them disadvantageous as industrial production methods.

Structure of the Invention In view of the current situation as described above, the present inventors have discovered that 2,3,5,6-
As a result of intensive research aimed at providing a method for producing tetrafluoro-4-mercaptobenzoic acid in high yield, we found that pentafluorobenzoic acid and a thiolating agent were heated to 40 to 100°C in an aqueous medium to produce tetrafluoro-4-mercaptobenzoic acid. - producing a salt of 4-mercaptobenzoic acid;
Then, they discovered that highly pure 2,3,5,6-tetrafluoro-4-mercaptobenzoic acid could be obtained in high yield by contacting the reaction mixture with an acidic substance, thereby completing the present invention. It came to this.

Hereinafter, specific embodiments of the present invention will be explained.

The present invention is completely different from the above-mentioned conventional technology, and the present invention is characterized in that pentafluorobenzoic acid and a thiolating agent (herein referred to as A thiolating agent is a basic inorganic compound containing a sulfur atom, and is used separately from the basic substances described below. The feature is that it is generated at a high rate.

When the reaction temperature is low, the solubility of the salt of pentafluorobenzoic acid is poor, and the reaction rate is significantly reduced.
Conversely, if the reaction temperature is high, tetrafluoro-
This is not preferred because large amounts of by-products such as isomers of 4-mercaptobenzoic acid, tetrafluoro-4-hydroxybenzoic acid, and decarboxylated products thereof are produced.

As the thiolating agent used in the present invention, alkali metal hydrogen sulfide, alkali metal sulfide, or a mixture thereof can be used.

The alkali metal hydrogen sulfide is, for example, at least one selected from the group consisting of sodium hydrogen sulfide, potassium hydrogen sulfide, and lithium hydrogen sulfide, and preferably sodium hydrogen sulfide and potassium hydrogen sulfide. The alkali metal hydrogen sulfide may be in either hydrated or anhydrous form.

The alkali metal sulfide is, for example, at least one selected from the group consisting of sodium sulfide, potassium sulfide, and lithium sulfide, and preferably sodium sulfide and potassium sulfide. The alkali metal sulfide may be in either hydrated or anhydrous form.

This first-stage reaction can also be carried out without the presence of a basic substance, which will be described later. In this case, the molar ratio of alkali metal hydrogen sulfide to pentafluorobenzoic acid is preferably in the range of 3:1 to 6:1, more preferably in the range of 3:1 to 4:1.

Furthermore, when using an alkali metal sulfide, the molar ratio of the alkali metal sulfide to pentafluorobenzoic acid is preferably in the range of 1.5:1 to 6:1, more preferably in the range of 1.5:1 to 3:1. It is.

When using either an alkali metal hydrogen sulfide thiolating agent or an alkali metal sulfide thiolating agent, if less than the lower limit of the above range is used for pentafluorobenzoic acid, the conversion of pentafluorobenzoic acid will be incomplete and side reactions will occur. also occurs.
Further, even if the amount is used in excess of the upper limit, no particularly advantageous effect is observed and it is economically disadvantageous.

Under the conditions specified above, it is possible to carry out the first stage reaction described above without the presence of the basic substance described below, but in this case, the amount necessary for converting pentafluorobenzoic acid to a thiol derivative is Since the above-mentioned alkali metal hydrogen sulfide or alkali sulfide is consumed and hydrogen sulfide, which is a highly toxic by-product, is generated, it is desirable to carry out the process in the presence of a basic substance, which will be described later. Next, a mode will be described in which this first stage reaction is carried out in the presence of a basic substance (the basic substance in this specification refers to a group of compounds excluding the above-mentioned thiolating agent).

An example of the first stage reaction when sodium hydroxide is used as the basic substance and sodium hydrogen sulfide is used for thiolation can be expressed as shown in the following formula (A).

The molar ratio of alkali metal hydrogen sulfide or alkali metal sulfide to pentafluorobenzoic acid is preferably 1:1 to 1.3:1, more preferably 1:
It is 1.

Amount of alkali metal hydrogen sulfide or alkali metal sulfide used relative to pentafluorobenzoic acid
Even if more than 1.3 times the molar amount is used, not only will it not bring about any particularly advantageous effect on the reaction, but it will also remain as an unreacted product after the reaction, and a large amount of hydrogen sulfide gas will be generated in the acid precipitation step described later, which will cause problems in the treatment. It requires a lot of labor, and if less than this molar amount is used, pentafluorobenzoic acid will remain unreacted in the product or the by-product tetrafluoro-4-hydroxybenzoic acid will be mixed in, reducing the purity of the product. Therefore, it is not desirable.

The purpose of using basic materials, as mentioned above, is to reduce the amount of expensive alkali metal hydrogen sulfide and alkali metal sulfide needed to convert pentafluorobenzoic acid to thiol derivatives, and to reduce the use of the highly toxic alkali metal sulfides. The aim is to eliminate the generation of hydrogen sulfide, which is a highly expensive by-product.

Therefore, any basic substance that exhibits the above-mentioned effects can be used without any particular restrictions, such as organic bases such as ammonia, triethylamine, and pyridine, and lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. alkali metal hydroxides, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, alkaline earth metals such as magnesium oxide and calcium oxide. Examples of inorganic bases include oxides of alkali metals, but from an industrial standpoint, it is desirable to use alkali metal hydroxides and/or carbonates.

The amount of the basic substance used is such that at least pentafluorobenzoic acid and the generated thiol are neutralized to form a salt of tetrafluoro-4-mercaptobenzoic acid such as intermediate () in reaction formula (A). More than enough amount is required. For example, when alkali metal hydrogen sulfide is used as a thiolating agent, the molar ratio of the alkaline substance to pentafluorobenzoic acid is preferably in the range of 2:1 to 5:1, more preferably 2:1 to 3:1. range. For example, when using an alkali sulfide as a thiolating agent, the molar ratio of the basic substance and pentafluorobenzoic acid should be within the range of 1:1 to 4:1 since the thiol described above takes a neutralized form. is preferable, more preferably 1:1 to 2:1
is within the range of If the amount of the basic substance used is less than the lower limit of the above range, hydrogen sulfide will be generated, which is undesirable, and if it is more than the upper limit, a considerable amount of tetrafluoro-4-hydroxybenzoic acid as a by-product will be produced. So I don't like it. on the other hand,
If the concentration of the alkaline substance is too high, it will be difficult for the raw materials to dissolve, so the concentration of the alkaline substance should be 5 to 5.
A range of 50% by weight is preferred.

Pentafluorobenzoic acid may be used in part or in its entirety as a salt of pentafluorobenzoic acid, which is a basic substance, as long as the stoichiometric ratio of the basic substance used is within the above-mentioned range. It is convenient to bring a predetermined amount of the basic substance into contact with pentafluorobenzoic acid in a clean water medium.

The reaction time varies depending on the reaction temperature, but is approximately 1
20 hours is appropriate.

Tetrafluoro- produced by the above first stage reaction
2,3,5,6-tetrafluoro-4-mercaptobenzoic acid is produced by bringing a reaction mixture containing a salt of 4-mercaptobenzoic acid into contact with an acidic substance, so-called acid precipitation.

As the acidic substance used for this acid precipitation, any substance can be used as long as it can neutralize the above-mentioned salt of tetrafluoro-4-mercaptobenzoic acid, but among them, sulfuric acid, which is generally used for acid precipitation, can be used. Alternatively, an aqueous solution of hydrochloric acid is suitable. The reaction mixture and the acidic substance may be brought into contact by adding the reaction mixture to an acidic aqueous solution, or vice versa.

2,3,5,6-tetrafluoro-4-mercaptobenzoic acid can be separated from the aqueous solution containing 2,3,5,6-tetrafluoro-4-mercaptobenzoic acid obtained after acid precipitation using, for example, ether, 2, using an extraction solvent such as methylene chloride or benzene.
It is also possible to extract 3,5,6-tetrafluoro-4-mercaptobenzoic acid into an organic layer, separate the layers, and then evaporate to dryness.

The 2,3,5,6-tetrafluoro-4-mercaptobenzoic acid obtained in this way can be used as a product as is, but it can be further purified by methods such as recrystallization to produce a product of higher purity. It can also be expressed as

EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.

Example 1 In a 300 ml four-necked flask equipped with a stirrer, a thermometer, a Dimroth condenser, and an addition funnel, 8.42 g (0.200 mol) of 95% sodium hydroxide dissolved in 100 g of water and pentane were added under a nitrogen atmosphere. After adding 21.28 g (0.100 mol) of fluorobenzoic acid and 8.00 g (0.100 mol) of 70% sodium hydrogen sulfide dissolved in 30 g of water, the temperature was maintained at 70-80°C under stirring for 5 hours. I reacted.

Next, after cooling, this reaction solution was poured into 100 ml of 6N aqueous hydrochloric acid solution to produce tetrafluoro-4-mercaptobenzoic acid. Tetrafluoro-4-mercaptobenzoic acid was extracted from the obtained aqueous solution containing tetrafluoro-4-mercaptobenzoic acid into an organic layer using 100 ml of diethyl ether. This extraction operation is done in 3
The obtained diethyl ether layer was dried over magnesium sulfate and then evaporated to dryness to obtain 21.42 g of tetrafluoro-4-mercaptobenzoic acid (yield 94.8 mol % based on pentafluorobenzoic acid).

Example 2 The same procedure as in Example 1 was performed except that 21.2 g of sodium carbonate was used instead of 95% sodium hydroxide. Tetrafluoro-4-mercaptobenzoic acid was 92%
It was obtained with a yield of mol%.

Example 3 95 mol% sodium hydroxide 5.05 g (0.12 mol),
and 28.8 g of sodium sulfide nonahydrate (Na ₂ S 9H ₂ O,
The same procedure as in Example 1 was carried out except that 0.12 mol) of tetrafluoro-4-mercaptobenzoic acid was used, and the
The yield was 71.2 mol%.

Example 4 Using the same reactor as in Example 1, 28.1 g (0.35 mol) of 70% sodium hydrogen sulfide dissolved in 130 g of water and 21.25 g of pentafluorobenzoic acid were prepared.
(0.100 mol) was added thereto, and the mixture was reacted for 5 hours while maintaining the temperature at 75 to 80°C while stirring. After cooling, the reaction mixture was gradually added to 100 ml of a 6N aqueous hydrochloric acid solution to precipitate tetrafluoro-4-mercaptobenzoic acid. Thereafter, the same procedure as in Example 1 was carried out, and tetrafluoro-4-mercaptobenzoic acid was obtained in a yield of 91.3 mol% based on the raw material pentafluorobenzoic acid.

Claims (1)

[Claims] 1. Tetrafluorobenzoic acid and a thiolating agent are heated to 40 to 100°C in an aqueous medium to form tetrafluoro-4
- 2,3,5,6-tetrafluoro-4-, characterized in that a salt of mercaptobenzoic acid is produced, and then the reaction mixture is contacted with an acidic substance.
Method for producing mercaptobenzoic acid. 2. The method according to claim 1, wherein the thiolating agent is at least one selected from the group consisting of alkali metal hydrogen sulfide and alkali metal sulfide. 3. The method according to claim 2, wherein the alkali metal hydrogen sulfide is sodium hydrogen sulfide and/or potassium hydrogen sulfide, and the alkali metal sulfide is sodium sulfide and/or potassium sulfide. 4. The method according to claim 1, 2 or 3, wherein a basic substance is present in the reaction mixture. 5. The method according to claim 4, wherein the basic substance is an inorganic base. 6. The method according to claim 4, wherein the basic substance is an alkali metal hydroxide and/or carbonate. 7. The method according to claim 4, wherein the basic substance is at least one selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.