JPS6136742B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula (In the formula, R represents an alkyl group having 1 to 10 carbon atoms, and R' represents a lower alkyl group.)
This invention relates to a method for producing esters. α-Fluoro-β-(alkylketo)esters, along with compounds having a fluoromethylene group such as α-fluoro-β-diketones and α-fluoro-β-diesters, are of interest from a biological standpoint as medicines, agricultural chemicals, etc. α-fluorocarbonyl or monofluoroheterocyclic compounds [for example, (a) REBanks ed. “Organofluorine Chemicals
and Their Industrial Applications”, Ellis
Horwood, London (1979) P.123, P154. (b) Edited by R. Filler, “Biochemistry Involving
Carbon‐Fluorine Bonds”, Am.Chem.Soc.
Washington (1976) P.23, P77]. Conventionally, methods for synthesizing α-fluoro-β-(alkylketo)esters represented by the above general formula () include 1. Leformatosky-type reaction of ethyl acetate and chlorofluoroacetate (J.
Chem.Soc., 1959 , 3278) 2 Method using Claisen-type reaction of fluoroacetate and acetyl chloride in the presence of a base such as sodium hydride or alkoxide etc. are known. However, these methods have a yield of 20% of the target α-fluoro-β-(alkylketo)esters.
The disadvantage is that the raw material compound fluoroacetic acid derivative and mercuric chloride are extremely toxic, causing problems in handling, and the raw material compound chlorofluoroacetic acid ester is difficult to obtain. However, it was impractical due to its shortcomings. As a result of intensive studies to solve these conventional drawbacks, the present inventors found that when Friedel-Crafts reaction is carried out using trifluoroethene, which is industrially inexpensive and easily available, the general formula (In the formula, R represents an alkyl group having 1 to 10 carbon atoms.) A polyfluoroalkyl ketone represented by the following formula is obtained, which is subjected to dehydrochlorination reaction and solvation reaction in an alcohol solvent in the presence of a basic compound. The inventors have surprisingly discovered that the desired α-fluoro-β-(alkylketo)esters represented by the above general formula () can be obtained under mild conditions and in high yields by carrying out a decomposition reaction, and have completed the present invention. It came to this. That is, the present invention is characterized in that a polyfluoroalkyl ketone represented by the general formula () is subjected to a dehydrochlorination reaction and a solvolysis reaction in one step in the presence of a basic compound in an alcohol solvent. α-Fluoro-β represented by the formula ()
- A method for producing (alkylketo)esters. The polyfluoroalkyl ketones represented by the general formula () used as raw materials in the method of the present invention include methyl=2-chloro-1,2,
2-trifluoroethyl ketone, propyl 2
-chloro-1,2,2-trifluoroethyl ketone, pentyl 2-chloro-1,2,2-trifluoroethyl ketone, nonyl 2-chloro-
Examples include 1,2,2-trifluoroethyl ketone. These polyfluoroalkyl ketones can be obtained by Friedel-Crafts reaction of trifluoroethene and excess acetyl chloride [Izvestia Academy Nauka SSR Selia Hiemicieska (Izv.Akad.
Nauk, SSSR, Ser. Khim., 1958 , 296], the present inventors selectively used dichloromethane as the solvent to free various aliphatic carboxylic acid chlorides and trifluoroethene. It has been found that it can be obtained in high yield by conducting a Del-Crafts reaction, and it has been obtained by this method. Further, examples of the basic compound used in the dehydrochlorination reaction and solvolysis reaction in the method of the present invention include relatively strong bases such as alkoxides and sodium hydroxide. The amount used must be at least three times the mole of the polyfluoroalkyl ketone represented by the general formula (). In practice, a range of 3.5 to 4 times the mole is appropriate. In addition, examples of the alcohol solvent used in the dehydrochlorination reaction and solvolysis reaction in the method of the present invention include methanol, ethanol, etc. The alcohol may contain water, and the amount used is as described above. There are no particular limitations on the polyfluoroalkyl ketone represented by the general formula (), but usually 2 to 3
is appropriate. The method of the present invention is carried out by adding a polyfluoroalkyl ketone represented by the general formula () to a basic compound and an alcohol solvent, and simultaneously performing a dehydrochlorination reaction and a solvolysis reaction. The reaction is completed in 1 to 2 hours at room temperature, and the reaction temperature is preferably room temperature. After the reaction, post-treatment may be carried out according to a conventional method, for example, by pouring into water, extracting with an organic solvent such as ether, and then treating with hydrochloric acid to decompose unreacted orthoester, followed by washing with water. α-fluoro-β-(alkylketo)esters can be obtained by well-known purification methods such as , solvent distillation, and distillation. General formula () produced by this reaction method
α-fluoro-β-(alkyl keto) represented by
Examples of esters include α-acetyl-α-
Examples include ethyl fluoroacetate, ethyl α-butyryl-α-fluoroacetate, ethyl α-heptanoyl-α-fluoroacetate, ethyl α-decanoyl-α-fluoroacetate, and the like. The method of the present invention is characterized by using raw materials that are industrially easily available at low cost and are not toxic to handle, and which can produce the desired α-fluorinated compound represented by the general formula () in a mild and high yield. -β-(alkylketo)ester can be produced, and the method has superior effects compared to conventional methods. Reference Example Synthesis of Polyfluoroalkyl Ketones 16.0 g (0.12 mol) of anhydrous aluminum chloride, 7.85 g (0.10 mol) of acetyl chloride, and 100 ml of dichloromethane were added to a pressure-resistant container under dry ice-acetone cooling. Next, 9.0 g (0.11 mol) of trifluoroethene was introduced into this, and 48
Stir for an hour and then pour onto a mixture of ice and 10 ml of concentrated hydrochloric acid. The organic layer was separated, washed with an aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Distill the residue to bp98−
10.2 g (yield 64%) of methyl 2-chloro-1,2,2-trifluoroethyl ketone at 100°C was obtained. Table 1 shows the results of producing various polyfluoroalkyl ketones using various aliphatic carboxylic acid chlorides in place of acetyl chloride.

[Table] Example 1 0.45 g (20 mmol) of sodium metal was dissolved in 10 ml of ethanol to produce sodium ethoxide, and then methyl 2-chloro-1,
2,2-trifluoroethyl ketone 0.80g
After adding (5 mmol), the mixture was stirred at room temperature for 2 hours to react. The resulting reaction mixture was poured into water and extracted with ether. Several drops of 1N hydrochloric acid were added, and after stirring at room temperature for 15 hours, the ether layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was distilled to give 0.65 g of ethyl α-acetyl-α-fluoroacetate at bp 102°C/53 mmHg (88% yield).
I got it. Examples 2 to 4 The results obtained in the same manner using various polyfluoroalkyl ketones in place of methyl 2-chloro-1,2,2-trifluoroethyl ketone are shown in the second example.
Shown in the table.

【table】

Claims (1)

[Claims] 1. In alcohol solvent, general formula (In the formula, R represents an alkyl group having 1 to 10 carbon atoms.) A dehydrochlorination reaction and a solvolysis reaction are performed on polyfluoroalkyl ketones represented by the following in the presence of a basic compound in one step. General formula for (In the formula, R represents the same meaning as above, and R' represents a lower alkyl group.) α-Fluoro-β-(alkyl keto)
Method for producing esters.