JP2696873B2 - Method for producing α-fluoro unsaturated aldehyde - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a general formula [I] useful as an intermediate for producing a fluorine-containing derivative of an insect pheromone and a fluorine-containing pyrethroid compound having insecticidal activity. ] [In the formula, R represents an alkyl group which may be substituted with a halogen atom. ] It concerns on the manufacturing method of (alpha) -fluoro unsaturated aldehyde shown by these.

<Prior Art> Conventionally, as a method for producing an α-fluoro unsaturated aldehyde, a method is known in which chlorofluorocarbene is added to an enol ether to obtain a cyclopropyl ether compound, and then hydrolysis is performed under heating.

For example, 2-methyl-1-propenyl methyl ether is reacted with chloroorcarbene generated from dichlorofluoromethane in an aqueous solution of potassium hydroxide to give 1-chloro-1-fluoro-2-methoxy-3,3-dimethyl. 2-Fluoro-3-methyl-2-butenal is prepared by obtaining cyclopropane and then heating the isolated cyclopropane compound to reflux in the presence of sodium dodecyl sulfate (Y. Bessire et al., Helv. Chim.Acta.60
Volume, 1789, 1977).

<Problems to be Solved by the Invention> However, in the above-mentioned method, (1) there is a problem in industrial availability of the enol ether used as a raw material. That is, it is generally known that an enol ether is synthesized by a two-step reaction via an acetal using a carbonyl compound as a starting material (for example, MS Newman et al., J. Org. Chem. 38, 2910, 197).
3 years), but there are many problems in the dealcoholization process by thermal decomposition from acetal, including the burden on industrial production equipment, such as the need for an extremely high number of rectification columns.

(2) A cyclopropyl ether compound obtained by adding chlorofluorocarbene to an enol ether is required to be once isolated and then separately subjected to a hydrolysis reaction in a different system, so that it is operationally complicated, and The hydrolysis reaction requires a long time under severe conditions of heating under reflux.

For these reasons, it is hardly necessarily advantageous in terms of economy, operability and the like, particularly as a production method on an industrial scale.

<Means for Solving the Problems> Under such circumstances, the present inventors have earnestly studied an advantageous method for producing an α-fluoro unsaturated aldehyde represented by the general formula [I], which is industrially advantageous. As a result, the present inventors have found that the aldehyde can be obtained by directly hydrolyzing in a reaction system without isolating a compound obtained by reacting morpholinoenamine with chlorofluorocarbene, leading to the present invention.

That is, the present invention relates to the general formula (II) [Wherein, R represents the same meaning as described above. Which provides a process for producing an α-fluoro unsaturated aldehyde represented by the above general formula [I] by adding chlorofluorocarbene to morpholino enamine represented by the formula and then hydrolyzing the resulting chlorofluorocyclopropyl morpholine compound. It is.

Note that chlorofluorocarbene can be generated from dichlorofluoromethane in the presence of a base.

 Hereinafter, the present invention will be described in more detail.

In the present invention, morpholino enamine used as a raw material can be obtained by reacting a corresponding aldehyde compound with two or more equivalents of morpholine in the presence of potassium carbonate (G. Stork et al., J. Am. Chem. Soc.85
Vol., 207, 1963).

In addition, chlorofluorocarbene can be generally generated from dichlorofluoromethane in the presence of a base. For example, dichlorofluoromethane can be produced in the presence of a phase transfer catalyst in an aqueous solution of an alkali hydroxide such as potassium hydroxide or sodium hydroxide. The reaction is carried out by reacting The amount of the alkali hydroxide used at that time is 2 equivalents or more, preferably 2.5 to 5.0 equivalents to morpholino enamine, and is usually used in a 30 to 60% aqueous solution. Examples of the phase transfer catalyst include tertiary amines such as tris (3,6-dioxaheptyl) amine; quaternary ammonium salts such as tetrabutylammonium bromide, benzyltriethylammonium chloride and phenyltriethylammonium chloride; 18-crown-6, dicyclohexano-
And crown ethers such as 18-crown-6. The amount of the phase transfer catalyst used is 0.005 equivalent or more, usually 0.01 to 0.1 equivalent, relative to dichlorofluoromethane.

The carbene addition reaction is usually carried out at −30 to 10 ° C., preferably −
The reaction is performed at a temperature of 10 to 5 ° C., and the reaction time depends on the blowing time of dichlorofluoromethane or the dripping time of the aqueous alkali hydroxide solution.

The subsequent hydrolysis reaction is performed at 10 to 70 ° C., preferably 20 to 50 ° C., and a reaction solvent is not essential, but if necessary, hydrocarbons such as hexane and toluene, ethers such as diethyl ether and tetrahydrofuran may be used. And an inert organic solvent.

The reaction solution after hydrolysis as described above is directly
The desired α-fluoro unsaturated aldehyde can be obtained by usual means such as separation of the product from the aqueous layer or extraction with a suitable organic solvent.

As the α-fluoro unsaturated aldehyde thus obtained, for example, those in which R in the general formula [I] is an ethyl group, an n-propyl group, an isopropyl group, a 2-fluoroethyl group, a 2-chloroethyl group, etc. No.

The α-fluoro unsaturated aldehyde obtained by the method of the present invention can be converted to a fluorinated insect pheromone derivative by reaction with a Wittig reagent (F. Camps).
Et al., Tetrahedron, 40, 2871, 1984).

Further, it can be converted to a secondary alcohol by reacting with an ethynyl Grignard reagent and then esterified to obtain a fluorinated pyrethroid compound having insecticidal activity (Japanese Patent Application Laid-Open No. Sho 61-280453, Japanese Patent Application No. Sho 62-28045). 116219
issue).

<Examples> Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 42.3 g of N- (1-butenyl) morpholine and tris (3,6
-Dioxaheptyl) amine 1.50 g, and mixed at -9 ° C.
A gas of 77.5 g of dichlorofluoromethane was blown in at to capture. The mixture was cooled to −14 ° C., and 113 g of a 54% aqueous potassium hydroxide solution was added dropwise. The dropwise addition was completed at -14 to -5C for 1 hour, and the temperature was kept at -5 to 2C for 3 hours. Then, the temperature was raised to 40 ° C. over 1 hour and kept at 40 ° C. for 6 hours. The reaction mixture was poured into 200 g of ice water, stirred for 10 minutes and separated.
The aqueous layer was extracted three times with 50 g of diethyl ether. All the organic layers were combined, and 140 g of cooled 18% hydrochloric acid was added thereto.
Stirred for hours. After liquid separation of the organic layer, the aqueous layer was extracted three times with 50 g of diethyl ether. The organic layers were all combined, washed once with 70 g of water and 70 g of saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 25.1 g of desired 2-fluoro-2-pentenal.

NMR (CDCl ₃ solvent, TMS internal standard) δ value (ppm) 1.13 (t, 3H), 2.10 to 2.75 (m, 10H) 5.99 (dt, 1H), 9.18 (d, 1H) Example 2 N- (1 -Pentenyl) morpholine 20.0 g and tris (3,6-dioxaheptyl) amine 1.25 g were mixed,
At 5 ° C., a gas of 36.0 g of dichlorofluoromethane was blown into and captured. Further, at 0 ° C., 48.0 g of a 54% aqueous solution of potassium hydroxide was added dropwise. The dropwise addition was completed at 0 ° C for 1 hour, and the temperature was kept at 0 to 5 ° C for 3 hours. Then 23 hours over 1 hour
The temperature was raised to 23 ° C. for 15 hours. The reaction mixture is added to ice water 10
0 g, stirred for 30 minutes and separated. The aqueous layer was extracted three times with 50 g of diethyl ether. All the organic layers were combined, and 140 g of 10% hydrochloric acid cooled was added thereto, followed by stirring at 20 ° C. for 2 hours.
After separating the organic layer, the aqueous layer was extracted three times with 30 g of diethyl ether. All the organic layers were combined, washed once with 40 g of water and 40 g of saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 11.8 g of desired 2-fluoro-2-hexenal.

NMR (CDCl ₃ solvent, TMS internal standard) δ value (ppm) 0.98 (t, 3H), 1.20 to 1.87 (m, 2H), 2.11 to 2.67 (m, 2H), 5.95 (dt, 1H), 9.20 (d , 1H) Example 3 N- (3-methyl-1-butenyl) morpholine 20.0 g
And 1.25 g of tris (3,6-dioxaheptyl) amine, and the mixture was trapped at -5 ° C. by blowing gas of 36.0 g of dichlorofluoromethane. Further, at 0 ° C., 48.0 g of a 54% aqueous solution of potassium hydroxide was added dropwise. The dropwise addition was completed at 0 ° C for 1 hour, and the temperature was kept at 0 to 5 ° C for 3 hours. Then, the temperature was raised to 23 ° C. over 1 hour and kept at 23 ° C. for 18 hours. The reaction mixture was poured into 100 g of ice water, stirred for 30 minutes, and separated. The aqueous layer was extracted three times with 50 g of diethyl ether. All the organic layers were combined, and 140 g of 10% hydrochloric acid cooled was added thereto, followed by stirring at 20 ° C. for 2 hours. After liquid separation of the organic layer, 30 g of diethyl ether was added to the aqueous layer.
, And the organic layers were all combined, washed once with 40 g of water and 40 g of saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 9.70 g of desired 2-fluoro-4-methyl-2-pentenal.

NMR (CDCl ₃ solvent, TMS internal standard) δ value (ppm) 1.10 (d, 6H), 2.59 to 3.41 (m, 1H), 5.82 (dd, 1H), 9.19 (d, 1H) <Effect of the Invention> The present invention relates to a process for producing an α-fluoro unsaturated aldehyde useful as an intermediate of a fluorine-containing derivative of an insect pheromone and an intermediate of a fluorine-containing pyrethroid compound having insecticidal activity. Can be manufactured.

Claims (1)

(57) [Claims] (1) General formula [In the formula, R represents an alkyl group which may be substituted with a halogen atom. A general formula characterized by adding chlorofluorocarbene to morpholino enamine represented by [Wherein, R represents the same meaning as described above. ] The manufacturing method of (alpha)-fluoro unsaturated aldehyde shown by these.