JP2719604B2 - Fluorine-substituted pyridine derivatives - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel fluorine-substituted pyridine derivative.

2. Description of the Related Art Some of the fluorine-containing heterocyclic compounds have strong physiological activity, for example, antibacterial or herbicidal action. Such compounds (for example, fluorine-containing pyrrolidone and its derivatives, fluorine-containing imidazole derivatives) , Fluorine-containing nucleic acid-related compounds, etc.) are used in the fields of medicine and agricultural chemicals.
In recent years, synthesis of various fluorinated heterocyclic compounds has been attempted by paying attention to such properties of fluorinated heterocyclic compounds, but a fluorine atom is selectively used as compared with another halogen atom such as a chlorine atom. The method for synthesizing a fluorine-containing heterocyclic compound is limited due to the difficulty of the substitution reaction.

An object of the present invention is to easily synthesize a novel fluorine-substituted pyridine derivative by a one-step reaction.

Means for Solving the Problems The present invention provides a compound of the general formula [I]: [In the formula, X is a 2-pyridine group, a 4-pyridyl group, an alkoxycarbonyl group, an N, N-dimethylcarbamoyl group, a phenyl group, a 2- (1,3-dithianyl) group or a 3-C ₁ -C
_{3 represents} an alkyl-5-isoxazolyl group, Y represents a phenyl group or a pyridyl group] and a process for producing the same.

Fluorine-substituted pyridine derivative represented by the general formula [I] is, for example perfluoro-2-methyl-2-pentene _{(CF 3) 2 C = CFC} 2 F 5 and the general formula N- silyl enamine represented by (II) non 4.5 hours in water solvent at -75 ° C, then
It is obtained by reacting at room temperature for 2 days.

However, the non-aqueous solvent may be an ordinary non-aqueous solvent such as ethers, acetonitrile, THF, DMF, and preferably diethyl ether or THF. The reaction time and the reaction temperature may be appropriately selected depending on the solvent. In addition, a method for synthesizing N-silylenamine represented by the general formula (II) can be easily prepared according to a previously reported synthesis example [Bulletin of Chemical Society of Japan]. Society
of Japan), 56, 1241-1242 (1983), by Takeo Konakahara et al.].

 This is represented by the following reaction formula.

[Wherein X and Y have the same meanings as above] The fluorine-substituted pyridine derivative according to the present invention described above has a significant physiological activity, and is particularly useful as a raw material for pharmaceuticals and agricultural chemicals.

 Hereinafter, the present invention will be described with reference to examples.

Example 1 4-fluoro-5- (3-methyl-5-isoxazolyl) -2-pentafluoroethyl-6-phenyl-3-
Synthesis of trifluoromethylpyridine 3-methyl-5- (trimethylsilyl) methylisoxazole (3.56 g, 0.02 mol) was added to a solution of THF (54 ml) in -7.
At 5 ° C., a 15% n-butyllithium hexane solution (9 g, 0.02
Mol) was slowly added dropwise. After stirring at −75 ° C. for 30 minutes, a solution of benzonitrile (2.2 g, 0.02 mol) in THF (10 ml) was slowly added dropwise, and the mixture was stirred at −75 ° C. for 1 hour and at room temperature for 2 hours to give N-silyl-1-yl. A solution of azaallyl anion in THF was obtained. The solution was cooled again to -75 ° C. and trifluoro-2-methyl-2-pentene (6.4 g, 0.02 mol) in THF
(10 ml) The solution was slowly added dropwise. Then at -75 ° C
After stirring for 4.5 hours at room temperature for 2 days, 50 ml of water was added under cooling to stop the reaction. The reaction mixture was extracted with ether,
After drying over anhydrous sodium sulfate, the solvent was removed to obtain a brown crude product. This crude product was purified by silica gel column chromatography (eluent: chloroform-ether system) to obtain the target product as yellowish white crystals in a yield of 52%.

Appearance: yellowish white crystals mp: 97.8-98.4 ° C. (recrystallized from hexane) IR (KBr method): Based on C-F absorption 1150~1310cm based ^-1 isoxazole absorption 1620,1400Cm ^-1 benzene ring or a pyridine ring Absorption based on 1580,1545,
^{1500,145cm -1 1 H-NMR (60MHz} , solvent: CCl _4, internal standard: TMS): δ 2.17 (3H , s) 5.66 (1H, s) 7.08 (5H, s) MS (70eV): m / z Molecular ion peak 440 Since this compound can lead the isoxazole ring to an α, β-unsaturated ketone [J. Org. Chem., 40 52
6 (1975)] It can be used as a starting material for compounds having a fluorinated pyridyl group.

Effect of the Invention The present invention makes it possible to obtain a novel fluorine-containing pyridine compound useful as a raw material for medicines, agricultural chemicals and the like by an extremely simple method.

Claims (2)

(57) [Claims] 1. A compound of the general formula [I]: [In the formula, X is a 2-pyridyl group, a 4-pyridyl group, an alkoxycarbonyl group, an N, N-dimethylcarbamoyl group, a phenyl group, a 2- (1,3-dithianyl) group or a 3-C ₁ -C
_{3 represents} an alkyl-5-isoxazolyl group, and Y represents a phenyl group or a pyridyl group]. 2. The general formula [II]: [In the formula, X is a 2-pyridyl group, a 4-pyridyl group, an alkoxycarbonyl group, an N, N-dimethylcarbamoyl group, a phenyl group, a 2- (1,3-dithianyl) group or a 3-C ₁ -C
_{3 represents} an alkyl-5-isoxazolyl group, and Y represents a phenyl group or a pyridyl group.] N-silylenamine and perfluoro-2-methyl-2-pentene are reacted in a nonaqueous solvent. General formula [I]: [Wherein X and Y have the same meanings as described above].