JPS61186363A - Production of pyridylpyridone derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound having anti-inflammatory, analgesic, antibacterial and insecticidal activities, etc., in high efficiency, at a relatively low temperature, without using a copper catalyst, by reacting a pyridine derivative with pyridone in the presence of a base. CONSTITUTION:The objective compound of formula III, e.g. [1(2H),3-chloro-5- trifluoromethyl-5'-trifluoromethyl-2'-bip-yridin]2-one is produced by reacting the compound of formula I (X is halogen; R1 and R2 are H, halogen, lower alkyl, NO2, CF3 or CN), e.g. 2-chloro-5-trifluoromethylpyridine, with the compound of formula II (R3 and R4 are H, halogen, lower alkyl, NO2, CF3 or CN), e.g. 3-chloro-5-trifluoromethyl-2-pyridone, in the presence of a base such as potassium carbonate, sodium hydride, etc., at 50-150 deg.C, preferably 70-120 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing pyridylpyridone derivatives, and more specifically, the present invention relates to a method for producing pyridylpyridone derivatives, and more particularly, compounds of the general formula (1) [wherein , R1, Rz, Rs and R4 are each the same or different and represent a hydrogen atom, a halogen atom, a lower alkyl group, a nitro group, a trifluoromethyl group or a cyano group. ] Pyridylpyridone derivative (
Hereinafter, it will be referred to as the compound of the present invention. ).

Generally, the following methods are generally known as methods for producing pyridylpyridone derivatives.

■ A method of reacting halogenopyridine, pyridone, and a gold steel catalyst at high temperatures (e.g., 200°C) (J,
Pharm, Soc, Japan, vol. 78.

1158 pages (1958).

(2) A method of reacting pyridine-N-oxide and halopyridine in the presence of an acid catalyst (Chem.

& Ind. (London), 1957, 46
page).

However, the above method (1) requires a copper catalyst and requires a reaction at a high temperature, and the method (2) has a low yield and isomer by-products. In this respect, it is difficult to say that the manufacturing method is necessarily sufficient.

Under these circumstances, the present inventors conducted various studies on the method for producing the compound of the present invention represented by the general formula (R), and found that a pyridine derivative having a trifluoromethyl group at the 5-position was used as a raw material. The present inventors have discovered that the compound of the present invention can be efficiently produced by carrying out the reaction in the presence of a base, without requiring a copper catalyst, and by the reaction at a relatively low temperature range, leading to the present invention.

That is, the present invention provides a general formula (n) in which X represents a halogen atom, and R1 and R2 have the same meanings as above. ] In the general formula (2) 1 formula, a pyridine derivative represented by
8 and R4 have the same meaning as above. ] The present invention provides a method for producing the compound of the present invention represented by the general formula (I) by reacting pyridone represented by the following in the presence of a base.

The method of the present invention will be explained in detail below.

In the method of the present invention, the bases include alkali metals,
Examples of the base include alkali metal hydrides and alkali metal salts, and examples of such bases include potassium carbonate, sodium hydride, and metallic sodium.

The reaction temperature is arbitrary in the range of 50 to 150°C depending on the type of base used, but usually a range of 70 to 120°C is sufficient to achieve the purpose.

In the method of the present invention, a reaction solvent is not essential, but a polar solvent can be used in order to make the reaction proceed more smoothly. Specific examples of such solvents include dimethylformamide, pyridine, dimethylacetamide, dimethylsulfoxide, and the like.

The amount of the reaction reagent used is usually 0.5 to 2.0 moles of pyridone represented by general formula (2) per 1 mole of pyridine derivative represented by general formula (II).

Although the reaction time may vary depending on the type of base used, the reaction temperature, and the presence or absence of a solvent, the objective can usually be achieved within a range of 2 to 48 hours.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Procedure A Add 100q (60%) of sodium hydride to 10-dimethylformamide, add 500q of 8-chloro-5-trifluoromethyl-2-pyridone to ξ at 20°C,
After stirring for 10 minutes, 2-chloro-5-
Add 600q of trifluoromethylpyridine and heat to 100℃
I stirred it for 24 hours. After cooling the reaction solution, place it on ice; 2
: and extracted with ethyl acetate. After washing the ethyl acetate layer with brine, the solvent was distilled off, and the resulting residue was subjected to silica gel column chromatography.
1), 8-chloro-5-trifluoromethyl-51-trifluoromethyl-21-bipyridin]-2-one (compound (1)) was obtained as white crystals.

Yield 680M! (Yield 78%) Melting point 146.2°C INMR (δ value, deuterated chloroform) 7.64 (d, 1) 1) 8.1 (2H) 8.85 (m, IH) 8.8 (IH) Example 2 Procedure B Potassium carbonate 1.52jF, dimethyl sulfoxide 20
m,5-trifluoromethyl-2-pyridone 1.63F
and 2.8Of of 2,8-dichloro-5-trifluoromethylpyridine were mixed and stirred at 70°C for 48 hours.

Thereafter, after performing the same post-treatment as in Example 1, it was subjected to silica gel column chromatography to obtain [1(2H), 5-
Trifluoromethyl-8'-chloro-5'-trifluoromethyl-2'-bipyridin]-2-one (compound (2)
)) was obtained as white crystals.

Yield 2.09 f (yield: 6196) Melting point 187
．． 8°C NMR (δ value, deuterated chloroform) 6.88 (IH, d) 7.6-8.0 (2H, m) 8.82 (IH, d) 8.98 (IH, S) Example 8 Procedure Method C Potassium carbonate 1.52f, 8-chloro-5-trifluoromethyl-2-pyridone 2. Of and 2.8 Of of 2,8-dichloro-5-trifluoromethylpyridine were mixed and stirred at 120°C for 24 hours. Thereafter, after performing the same post-treatment as in Example 1, it was subjected to silica gel column chromatography to obtain [1(2H),8-chloro-5-trifluoromethyl-8'-chloro-5'-trifluoromethyl- 2'-bipyridin]-2-one (compound (8))
was obtained as white crystals.

Yield: 2.45 IC yield: 65%) Melting point: 108.5°C NMR (δ value, deuterated chloroform) 7.77 (2H, s) 8.19 (IH) 8.77 (LH) Below, according to the method of the present invention Examples of the obtained compounds are shown below.

Pot Substituents R1, Rz of the compound represented by the above general formula,
Written amendment to the contents and procedures of Rs, R4゜RIs and R6 (voluntary) August 2r, 1985 l Indication of the case 1985 Patent Application No. 26882 2. Name of invention Process for producing pyridylpyridone derivatives 3. Amendments made Address related to the incident: 5-15 Kitahama, Higashi-ku, Osaka Name (20
9) Hijikata, Representative of Sumitomo Chemical Industries, Ltd.
Takeshi 4, agent

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, X represents a halogen atom, R_1 and R_
2 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a nitro group, a trifluoromethyl group or a cyano group. ] Pyridine derivatives represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. Represents a methyl group or a cyano group. ] A general formula characterized by reacting a pyridone represented by . ] A method for producing a pyridylpyridone derivative.