JPH10101659A - Production of substituted thiazolidine-dione derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a substituted thiazolidine-dione derivative at a high yield by using a material easy to be produced by catalytic hydrogenation of a benzylidenethiazolidine-dione derivative in the presence of a nickel-containing catalyst in a specific alcohol-based solvent. SOLUTION: This substituted thiazolidine-dione derivative of formula II is produced by hydrogenation of a benzylidenethiazolidine-drine derivative of formula I (R<1> and R<2> are each H, OH, a straight or branched chain alkyl, etc.), for example, 5-benzylidenethiazolidine-2,4-dione, in the presence of a nickel- containing catalyst (preferably Raney nickel, etc.) preferably in a quantity of (1:10) to (1:100) to the compound of formula I, in a C2 or lower alcohol-based solvent (preferably methanol) at temperature of 0-40 deg.C, preferably at 0-30 deg.C, preferably at a hydrogen pressure of 10-50kg/cm<2> for 0.5-6 hours of reaction time.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a substituted thiazolidinedione derivative. The compounds obtained by the present invention are useful as raw materials for medicines, agricultural chemicals and the like.

[0002]

2. Description of the Related Art As a method for producing a substituted thiazolidinedione derivative, an α-halo-β-phenylpropionic acid derivative is reacted with thiourea and then hydrolyzed (for example, see Chemical Pharmaceutical Bulletin, 30 , 3563 (198).
2)) is known. However, this method uses the α-
There are drawbacks in that it is difficult to obtain a halo-β-phenylpropionic acid derivative, a complicated process is required for its production, and a copper catalyst that is difficult to dispose must be used.

[0003] Since benzylidenethiazolidinedione derivatives contain sulfur in the molecule, they are difficult to be reduced by the catalytic poisoning of sulfur by ordinary hydrogenation, and S is also reduced by desulfurization.
It is known that bond cleavage occurs (eg, Or
g. Reactions, 12 , 356 (1962)). When palladium is used as a catalyst for catalytic hydrogenation (Tokuhei 6-503353)
No. 2) tends to decrease the catalytic activity, and it is economically disadvantageous that a catalyst having the same weight or more as the raw material must be used.

The inventors of the present invention have found that when a benzylidene thiazolidinedione derivative is hydrogenated in the presence of a catalyst such as nickel or cobalt, the S bond in the ring is cleaved or removed despite the presence of the S bond in the ring. A method for producing a target benzylthiazolidinedione derivative by selectively hydrogenating a double bond without separation was found (Japanese Patent Application No. 7-103220). However,
The reaction concentration could not be increased so much, and the efficiency of the apparatus was not satisfactory.

[0005]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned various problems of the prior art, and an object of the present invention is to use a benzylidenethiazolidinedione derivative which is easy to produce as a raw material and to provide a high yield. To provide a method by which a benzylthiazolidinedione derivative can be produced.

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, have found that a benzylidene thiazolidione derivative can be converted into a catalyst containing nickel in an alcohol solvent having 2 or less carbon atoms. The present inventors have found that the desired substituted thiazolidione derivative can be produced in high yield by catalytic hydrogenation in the presence of the compound, and have reached the present invention.

That is, the present invention provides a compound represented by the general formula (1): (Wherein, R ¹ and R ² are the same or different and each represents a hydrogen atom, a hydroxyl group, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms) Group, or R ¹ and R ² together represent a methylenedioxy group) to produce a substituted thiazolidinedione derivative represented by the general formula (2) (Wherein R ¹ and R ² are as defined above),
The present invention relates to a method for producing a substituted thiazolidinedione derivative, which comprises hydrogenating an alcohol solvent having 2 or less carbon atoms in the presence of a catalyst containing nickel at a temperature of 0 to 40 ° C.

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
The benzylidenethiazolidinedione derivative represented by the general formula (2) used as a raw material in the present invention is, specifically, 5-benzylidenethiazolidine-2,4-dione,
5- (4-hydroxybenzylidene) thiazolidine-
2,4-dione, 5- (4-methoxybenzylidene) thiazolidine-2,4-dione, 5- (4-ethoxybenzylidene) thiazolidine-2,4-dione, 5- (4-
Methylbenzylidene) thiazolidine-2,4-dione;
5- (4-t-butylbenzylidene) thiazolidine-
2,4-dione, 5- (3,4-methylenedioxybenzylidene) thiazolidine-2,4-dione, 5- (3-
(Hydroxybenzylidene) thiazolidine-2,4-dione, 5- (3-methoxybenzylidene) thiazolidine-
2,4-dione, 5- (3-methylbenzylidene) thiazolidine-2,4-dione, 5- (2-hydroxybenzylidene) thiazolidine-2,4-dione, 5- (2-
(Methoxybenzylidene) thiazolidine-2,4-dione, 5- (2-methylbenzylidene) thiazolidine-
2,4-dione, 5- (3,4-dihydroxybenzylidene) thiazolidine-2,4-dione, 5- (3,4-
Dimethoxybenzylidene) thiazolidine-2,4-dione, 5- (3-hydroxy-4-methoxybenzylidene) thiazolidine-2,4-dione, 5- (4-hydroxy-3-methylbenzylidene) thiazolidine-2,4
-Dione and the like.

These benzylidene thiazolidine derivatives can be easily obtained by dehydrating and condensing the corresponding benzaldehyde derivative with thiazolidine-2,4-dione.

[0010] The catalyst used in the present invention contains nickel. The present catalyst can be used as a simple substance of these metals or a compound such as a salt such as a nitrate, a sulfate or a chloride, an oxide or a hydroxide thereof. Further, it can be used by being supported on a carrier. in this case,
Activated carbon, silica, alumina, silica-alumina and the like are used as the carrier, and the amount of the supported catalyst is 5 to 70% by weight.
It is good to use within the range. Specific examples of preferred catalysts include Raney nickel, nickel-silica gel, nickel-alumina and the like.

The amount of the catalyst used is usually in the range of 1 to 1/1000 weight, preferably 1/10 to 1/100 weight, based on the benzylidene thiazolidine derivative as the raw material.

The reaction solvent in the method of the present invention includes:
Alcohol-based solvents having 2 or less carbon atoms, such as methanol and ethanol, have high solubility of the benzylidenethiazolidione derivative as a raw material and can be set to have a high reaction concentration. Particularly, methanol is preferable from the viewpoint of economy.

The reaction temperature is in the range of 0 to 40 ° C., but at a higher temperature, the formed substituted diazolidinedione derivative tends to be decomposed. The preferred reaction temperature is 0 to 35 ° C, more preferably 0 to 30 ° C. Hydrogen pressure reaction is applied in the range of usually 1 to 100 kg / cm ^2, the range of 10 to 50 kg / cm ² is preferred. The reaction time varies depending on the reaction conditions such as the amount of the catalyst, the reaction temperature, and the hydrogen pressure.
It is applied in the range of 0.5 to 6 hours.

The benzylthiazolidinedione derivative produced by the method of the present invention can be separated and purified from the reaction system by general operations such as distillation, recrystallization and extraction.

[0015]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

The synthesis of the starting benzylidenethiazolidinedione derivative is shown as a reference example. Reference Example 5- (4-hydroxybenzylidene) thiazolidine-
Synthesis of 2,4-dione 122.2 g of 4-hydroxybenzaldehyde, 117.2 g of thiazolidine-2,4-dione, 8 of piperidine.
5 g, 6.0 g of acetic acid and 2,000 ml of toluene were mixed and heated under reflux for 2 hours. After the reaction, the reaction solution was cooled to room temperature, and the precipitated crystals were filtered.
Washed with 0 ml. The obtained crystals were dried under vacuum to give 5-
(4-hydroxybenzylidene) thiazolidine-2,4
198.8 g of yellow crystals of -dione were obtained.

EXAMPLE 1 10 g of 5- (4-hydroxybenzylidene) thiazolidine-2,4-dione and 150 g of methanol were placed in a pressurized reaction vessel.
Then, 3.5 g of Raney nickel was added, the inside of the vessel was replaced with hydrogen, and the mixture was stirred at a hydrogen pressure of 30 kg / cm ² and 30 ° C. for 1 hour. After the reaction, the reaction mixture was filtered to remove the catalyst, and the filtrate was concentrated under reduced pressure to give 5- (4-hydroxybenzyl) thiazolidine-2,4-dione as colorless crystals.
0.1 g was obtained. The yield was 99%.

Examples 2 to 9 The corresponding substituted thiazolidinedione derivatives were produced in the same manner as in Example 1, except that the starting benzylidenethiazolidinedione derivative was changed to those shown in Table 1 below. The raw materials and the reaction times are shown in Table 1, and the target products and the yields are shown in Table 2.

Table 1 Example Raw material Reaction time Benzylidenethiazolidinedione derivative (Hr) ────────────────────────────────────25- (4-methoxybenzylidene) thiazolidine- 2,4-dione 23 5- (4-ethoxybenzylidene) thiazolidine-2,4-dione 14 5- (3-hydroxybenzylidene) thiazolidine-2,4-dione 25 5- (3,4-methylenedi Oxybenzylidene) thiazolidine-2,4-dione 26 5- (3,4-dihydroxybenzylidene) thiazolidine-2,4-dione 47 5- (2-hydroxybenzylidene) thiazolidine-2,4-dione 28 5- Benzili Denthiazolidine-2,4-dione 29 5- (4-methylbenzylidene) thiazolidine-2,4-dione 2} ────────────

Table 2 Example Example Target Product Yield Substituted Thiazolidine Dione derivative (%) ──────────────────────────────────── 25- (4-methoxybenzyl) Thiazolidine-2,4-dione 98 3 5- (4-ethoxybenzyl) thiazolidine-2,4-dione 97 4 5- (3-hydroxybenzylidene) thiazolidine-2,4-dione 955 5- (3,4- Methylenedioxybenzylidene) thiazolidine-2,4-dione 93 6 5- (3,4-dihydroxybenzylidene) thiazolidine-2,4-dione 92 7 5- (2-hydroxybenzylidene) thiazolidine-2,4-dione 958 5-benzylidene Thiazolidine-2,4-dione 96 9 5- (4-methylbenzylidene) thiazolidine-2,4-dione 97 ───────────

Comparative Example 1 10 g of 5- (4-hydroxybenzylidene) thiazolidine-2,4-dione and 150 g of methanol were placed in a pressurized reaction vessel.
Then, 3.5 g of Raney nickel was added, the inside of the vessel was replaced with hydrogen, and the mixture was stirred at 30 kg / cm ^{2 of} hydrogen at 50 ° C. for 3 hours. After the reaction, the reaction mixture was filtered to remove the catalyst, and the filtrate was concentrated under reduced pressure to obtain 8.8 g of a yellow solid, which was the target 5- (4-hydroxybenzyl) thiazolidine- 2,4-dione and 5-
(4-hydroxybenzylidene) thiazolidine-2,4
A mixture having a dione ratio of 4: 1. An attempt was made to purify this mixture by recrystallization, but it was difficult to remove the raw materials.

According to the method of the present invention, a benzylidenethiazolidinedione derivative which is easy to produce is used as a raw material,
A substituted thiazolidinedione derivative can be produced in high yield without requiring special operations or equipment.

Claims (3)

[Claims] 1. The general formula (1) (Wherein, R ¹ and R ² are the same or different and each represents a hydrogen atom, a hydroxyl group, a linear or branched alkyl group having 1 to 4 carbon atoms, a linear or branched alkoxy group having 1 to 4 carbon atoms) Group, or R ¹ and R ² together represent a methylenedioxy group) to produce a substituted thiazolidinedione derivative represented by the general formula (2) (Wherein R ¹ and R ² are as defined above),
A method for producing a substituted benzylthiazolidinedione derivative, comprising hydrogenating an alcoholic solvent having 2 or less carbon atoms in the presence of a catalyst containing nickel at a temperature of 0 to 40 ° C. 2. The method according to claim 1, wherein the temperature of the hydrogenation is from 0 to 35 ° C. 3. The method according to claim 1, wherein the temperature of the hydrogenation is 0 to 30 ° C.