JPS6136743B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula (In the formula, R represents a phenyl group or a phenyl group substituted with a chlorine atom, a methyl group, or a dimethylamino group, and R' represents a lower alkyl group.)
This invention relates to a method for producing esters. α-Fluoro-β-(arylketo)esters, along with compounds having active fluoromethylene groups 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, P.77]. Conventionally, α-fluoro- A method for synthesizing β-(arylketo)esters is a Claisen-type reaction between ethyl monofluoroacetate and benzoyl chloride in the presence of a base such as sodium hydride or an alkoxide. (J.Chem.Soc., 1959 , 3278) is known. However, this method is not suitable for the target α-fluoro-β
- Yield of (arylketo)esters is 20-30%
However, the raw material compound ethyl monofluoroacetate is extremely toxic, which poses problems in handling and is impractical. As a result of intensive studies to solve these conventional drawbacks, the present inventors obtained a hexafluoropropene-diethylamine adduct by reacting hexafluoropropene and diethylamine, which are industrially available at low cost and easily. , then hydrolyze this N,
By obtaining N-diethyl-1,2,2,2-tetrafluoropropionamide and further reacting it with a Grignard reagent, the general formula (In the formula, R has the above-mentioned meaning.) A polyfluoroalkyl ketone represented by the formula is obtained, and this is subjected to a dehydrofluorination reaction and a solvolysis reaction in an alcohol solvent in the presence of a basic compound. Surprisingly, the inventors discovered that the desired α-fluoro-β-(arylketo)esters represented by the above general formula () can be obtained under mild conditions and in high yields, leading to the completion of the present invention. . That is, the present invention is characterized in that the polyfluoroalkyl ketones represented by the general formula () are subjected to a dehydrofluorination reaction and a solvolysis reaction in one step in the presence of a basic compound in an alcohol solvent. α-Fluoro- represented by the general formula ()
This is a method for producing β-(arylketo)esters. The polyfluoroalkyl ketones represented by the general formula () used as raw materials in the method of the present invention include phenyl=1,2,2,2-tetrafluoroethyl ketone, 4-fluorophenyl=1,2 ,2,2-tetrafluoroethyl=
Ketone, 4-chlorophenyl = 1,2,2,2-
Tetrafluoroethyl=ketone, 4-methylphenyl=1,2,2,2-tetrafluoroethyl=
Ketone, 4-methoxyphenyl = 1,2,2,2
-tetrafluoroethyl ketone, 4-dimethylaminophenyl 1,2,2,2-tetrafluoroethyl ketone, 3-methylphenyl 1,
Examples include 2,2,2-tetrafluoroethyl ketone. These polyfluoroalkyl ketones are produced by a method of reacting hexafluoropropene with diethylamine [Bull.Chem.Soc., Jpn.,
52 , 3377 (1979)], N,N-diethyl-1,2,2,
2-tetrafluoropropionamide was obtained, which was further heated at -40 to -30°C in tetrahydrofuran.
It can be obtained by reacting with Grignard reagent at Examples of the basic compound used in the dehydrofluorination 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 (). Practically speaking, a range of 3.5 to 4 times the mole is appropriate. In addition, examples of the alcohol solvent used in the dehydrofluorination reaction and solvolysis reaction in the method of the present invention include alcohols such as methanol and ethanol, and the alcohol may contain water; The amount used is not particularly limited for the polyfluoroalkyl ketone represented by the general formula (), but usually 1
2 to 3 per mole is suitable. 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 dehydrofluorination 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, the reaction mixture obtained is poured into water, extracted with an organic solvent such as ether,
Next, unreacted orthoesters are decomposed by treatment with hydrochloric acid, followed by washing with water, and α-fluoro-β-(arylketo)esters can be obtained by known purification methods such as solvent distillation and distillation. General formula () produced by this reaction method
α-fluoro-β-(arylketo) represented by
Examples of esters include α-benzoyl-α
-Methyl fluoroacetate, α-benzoyl-α-ethyl fluoroacetate, α-(4-fluorobenzoyl)-α-methyl fluoroacetate, α-(4-chlorobenzoyl)-α-methyl fluoroacetate, α-(4-fluorobenzoyl)-α-methyl fluoroacetate, α-(4-fluorobenzoyl)-α-methyl fluoroacetate,
-methylbenzoyl)-α-methyl fluoroacetate, α-(4-methoxybenzoyl)-α-methyl fluoroacetate, α-(4-dimethylaminobenzoyl)-α-methyl fluoroacetate, α-(3-methylbenzoyl) -α-methyl fluoroacetate and the like. The method of the present invention is characterized by using raw materials that are industrially inexpensive, easily obtainable, and non-toxic to handle, and can be used in a mild manner and in high yields to produce the desired α-fluorocarbon compound represented by the general formula (). -β-(arylketo)ester is produced, and has superior effects compared to conventional methods. Reference example 1 Stirrer, thermometer, reflux condenser (dry ice)
Add 105 g (1.4 mol) of diethylamine and 200 ml of dry ether to a round-bottomed flask equipped with a gas inlet tube extending into the liquid, cool to 0-5°C, and add gas at below 10°C while stirring. 240 g (1.6 mol) of hexafluoropropene was introduced from the inlet over 2 hours and reacted. After the reaction, the reaction mixture was left overnight at room temperature, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain a hexafluoropropene-diethylamine adduct (Et ₂ NCF ₂ CHFCF ₃ :Et ₂ NCF=CFCF ₃ =1:
1) 273g (yield 89%) was obtained. Reference Example 2 21 g (0.1 mol) of the hexafluoropropenediethylamine adduct obtained in Reference Example 1 was gradually added dropwise to 250 g (0.1 mol) of a 5% aqueous sodium hydrogen carbonate solution, and after stirring for an additional 30 minutes, the oil layer was extracted with ether. After washing with water, dry with anhydrous magnesium sulfate,
The solvent was distilled off, and the residue was distilled under reduced pressure to give N,N-diethyl-
1,2,2,2-tetrafluoropropionamide was obtained. Reference Example 3 Magnesium strips in 80 ml of dry tetrahydrofuran were placed in a 500 ml round bottom flask equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser under a stream of nitrogen.
Grignard reagent prepared from 4.4 g (180 mg atoms) and 28.3 g (180 mmol) of bromobenzene in 50 ml of tetrahydrofuran in 50 ml of tetrahydrofuran.
N,N-diethyl-1,2, obtained in Reference Example 2
2,2-tetrafluoropropionamide 20.1g
(100 mmol) was gradually added dropwise at -40 to -30°C, and the temperature was maintained at -40 to -30°C for an additional hour. The reaction mixture was decomposed with ice water, neutralized with concentrated hydrochloric acid, extracted with ether, washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was distilled under reduced pressure to obtain bp. Phenyl = 85−87℃/18mmHg
1,2,2,2-tetrafluoroethyl ketone
11.2g (66% yield) was obtained. Table 1 shows the results of producing various polyfluoroalkyl ketones using various aryl bromides in place of bromobenzene.

【table】

[Table] Example 1 Phenyl = 1,2,2,2-tetrafluoroethyl = ketone 2.06g (10 mmol) and methanol
10ml and 2N sodium hydroxide aqueous solution 18ml
was added and stirred at room temperature for 1 hour to react. The reaction mixture was treated with concentrated hydrochloric acid, extracted with ether, washed with water, and dried over anhydrous magnesium sulfate.
The solvent was removed under reduced pressure, and the residue was removed under reduced pressure to obtain bp144.
1.71 g (yield: 87%) of methyl α-benzoyl-α-fluoroacetate was obtained at −145° C./10 mmHg. Example 2 The procedure was the same as in Example 1 except that ethanol was used instead of methanol. bp.120-121℃/12
1.49 g (yield 71%) of ethyl α-benzoyl-α-fluoroacetate was obtained at mmHg. Examples 3 to 8 Table 2 shows the results of reacting various polyfluoroalkyl ketones under the same reaction conditions as in Example 1.

【table】

【table】

Claims (1)

[Claims] 1. In alcohol solvent, general formula (In the formula, R represents a phenyl group, or a phenyl group substituted with a chlorine atom, a methyl group, or a dimethylamino group.) General formula characterized by carrying out the solvolysis reaction in one step (In the formula, R represents the same meaning as above, and R' represents a lower alkyl group.) α-fluoro-β-(arylketo) represented by
Method for producing esters.