JPH0656734A - 1-hydroxy-2,2,2-trifluoroethyl alkyl ketone and its production - Google Patents

Abstract

PURPOSE:To efficiently obtain this readily handleable compound useful as an intermediate raw material for a ferroelectric liquid crystal, a building blocking agent, etc., from easily obtainable starting raw materials in a high yield. CONSTITUTION:Trifluorolactic acid ethyl ester of formula I is reacted with a Grignard reagent of formula II (R is a 3-10C straight-chain alkyl) at -100 to -40 deg.C to give an alkoxide intermediate of formula III. The intermediate of formula III is hydrolyzed with a mineral acid, preferably hydrochloric acid to give a fluorine-containing compound of formula IV such as 1-hydroxy-2,2,2- trifluoroethyl butyl ketone. The first-stage reaction of the reaction is preferably carried out by dripping a solution of the compound of formula II in an ether solvent to a solution of the compound of formula I in an ether solvent in terms of sufficient yield.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The present invention is useful, for example, as an intermediate raw material for ferroelectric liquid crystal which is a raw material for electronic devices, or as a building block agent capable of introducing various functional groups into compounds used for pharmaceuticals and agricultural chemicals. Which relates to a novel method for producing a fluorine-containing compound.

[0002]

As a fluorine-containing carbonyl compound useful as a building block agent, 2-alkoxy-3,
3,3-trifluoroethyl methyl ketone is known. However, this compound has a low boiling point and high volatility, which makes it difficult to handle. Therefore, there is a demand for a fluorine-containing carbonyl compound which is easy to handle and versatile.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have proposed a novel fluorine-containing carbonyl compound represented by the formula (1), which is expected as a raw material for a liquid crystal compound having ferroelectricity and is useful as a building block agent or the like. The present invention was completed as a result of intensive research on a method for producing the compound using an invented and easily available raw material.

[0004]

[Chemical 2]

[0005]

The present invention is characterized in that trifluorolactic acid ethyl ester is reacted with a Grignard reagent represented by the formula (2), and then the reaction product is hydrolyzed with a mineral acid. 1-shown by equation (1)
It is a method for producing hydroxy-2,2,2-trifluoroethyl alkyl ketone.

[0006]

[Chemical 3]

RMgBr (2) (In the formula, R is a linear alkyl group having 3 to 10 carbon atoms and corresponds to R in the formula (1).)

In the compound represented by the formula (1) in the present invention (hereinafter also referred to as the compound of the present invention), the alkyl group represented by R in the formula is an alkyl group having 3 to 10 carbon atoms,
That is, n-propyl, n-butyl, n-pentyl,
Among them, n-hexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl are useful compounds, and R is a straight-chain alkyl group having 4 to 8 carbon atoms because of its ease of production. is there. Specific examples of the compound that can be advantageously produced in the present invention are 1-hydroxy-2,2,2-trifluorobutyl ketone, 1-hydroxy-2,2,2-trifluoropentyl ketone, and 1-hydroxy-2. , 2,2-trifluorohexyl ketone, 1-hydroxy-2,2,
2-trifluoroheptyl ketone, 1-hydroxy-
It is 2,2,2-trifluorooctyl ketone.

In the present invention, trifluorolactic acid ethyl ester (hereinafter also referred to as starting compound) is added to the Grignard reagent represented by the formula (2) (hereinafter referred to as Grignard reagent).
Are first added to cause a reaction (first-step reaction), and then the reaction product is hydrolyzed with a mineral acid (second-step reaction). RMgBr (2) (In the formula, R is a linear alkyl group having 3 to 10 carbon atoms and corresponds to R in the formula (1).)

The production method from the starting compound will be described in detail below. [First-step reaction] The first-step reaction is represented by the reaction formula (3).
And the reaction first produces the alkoxide intermediate.

[0011]

[Chemical 4]

The reaction of the formula (3) is carried out by adding dropwise a solution of the Grignard reagent in an ether solvent to a solution of trifluorolactic acid ethyl ester in an ether solvent. It is preferable in that it can be obtained.

On the contrary, when trifluorolactic acid ethyl ester is added dropwise to the Grignard reagent, the compound represented by the formula (4) becomes the main component, and the yield of the desired product is remarkably reduced.

[0014]

[Chemical 5]

The Grignard reagent is represented by the above formula (2), wherein R corresponds to R of the formula (1) in the compound of the present invention. If the alkyl group has more than 10 carbon atoms, it is difficult to prepare the Grignard reagent.

The mixing ratio of the Grignard reagent and the ether solvent is preferably 1,000 ml to 4,000 ml of ether and particularly preferably 2,000 ml to 3,000 ml with respect to 1 mol of the Grignard reagent. 1 ether
If it is less than 4,000 ml, side reactions are likely to occur and 4,000 ml
If it exceeds, it will not be economical.

Examples of the ether solvent include diethyl ether, diglyme, THF and the like, and diethyl ether is particularly preferable.

The preferred mixing ratio of trifluorolactic acid ethyl ester and ether solvent is 3,000 ml of ether to 1 mol of trifluorolactic acid ethyl ester.
7,000 ml, particularly preferably 4,000 ml-
It is 6,000 ml. If the amount of ether is less than 3,000 ml, side reactions may proceed, and if it exceeds 7,000 ml, it cannot be said to be economical.

The trifluorolactic acid ethyl ester and the Grignard reagent are supplied at a ratio of 1.9 to 2.
1 mol is preferred. If the amount of the Grignard reagent is less than 1.9 mol, the yield of the alkoxide intermediate may decrease,
If the amount exceeds 2.1 mol, the Grignard reagent further reacts with the carbonyl group of the alkoxide intermediate in the above formula (3) to produce the by-product represented by the above formula (4), and the yield of the desired product is increased. Lead to a decline.

The feed rate of the Grignard reagent to trifluorolactic acid ethyl ester is preferably such that 1 mol of the Grignard reagent is added dropwise over about 300 to 500 minutes.
If the feeding time is short, a side reaction for forming the compound of the above formula (4) may proceed, and the yield of the desired addition product may be reduced. Will be less advantageous.

The reaction temperature of the formula (3) is -40 ° C to -100.
C is preferred. Since the temperature can be kept at -78 ° C by using a dry ice-acetone bath, it is industrially particularly advantageous to carry out the reaction at this temperature. When the temperature is lower than -100 ° C, the reaction product takes a long time because the production rate of the desired alkoxide intermediate is slow, and when the temperature is higher than -40 ° C, a side reaction proceeds and the yield of the addition product decreases. .

After the completion of supplying the Grignard reagent to the reaction system, the mixture is stirred for about 2 hours to sufficiently react the unreacted trifluorolactic acid ethyl ester to form an alkoxide intermediate.

[Second Stage Reaction] An example of the reaction formula of the second stage reaction is shown in formula (5) when hydrochloric acid is used as the mineral acid, and the alkoxide obtained in the first stage reaction is The intermediate is hydrolyzed with mineral acid to form the desired compound.

[0024]

[Chemical 6]

Examples of the mineral acid include hydrochloric acid, sulfuric acid, nitric acid and the like, and a particularly preferred mineral acid is hydrochloric acid. The mineral acid is preferably 2 to 3 gram equivalent with respect to 1 mol of trifluorolactic acid ethyl ester used as a raw material. If it is less than 2 gram equivalent, hydrolysis of the addition product tends to be gram, and if it exceeds 3 gram equivalent, it is not economical.

When hydrolyzing with a mineral acid, the concentration of the mineral acid is preferably 1 to 5N. If it is less than 1N, the amount of the aqueous layer is large, so that the target substance is also dissolved in the aqueous layer, the extraction operation becomes complicated, which is not economical, and there is a possibility that an undesired side reaction proceeds. If it exceeds 5N, there is a possibility that the amount of by-products will increase.

The hydrolysis reaction is generally carried out by dropping an aqueous solution of a mineral acid into the reaction solution obtained in the first-step reaction, but the reaction obtained in the first-step reaction is added to the aqueous solution of a mineral acid. The method of dropping the liquid may be used.

The hydrolysis reaction is preferably carried out at a temperature as mild as possible, and room temperature is particularly suitable. If the temperature is too high, there is a risk that the solvent, ether, may catch fire, and side reactions may proceed.

After the dropping of the mineral acid, the reaction may be completed by leaving the mixture to stir at room temperature for 30 minutes or more.

After completion of the hydrolysis reaction, the target product was separated from the reaction solution by an operation such as extraction with ether, and anhydrous magnesium sulfate was added to the extraction solution to remove water, and then the solvent was distilled off under reduced pressure to remain. The syrup-like substance can be purified by column chromatography or the like to obtain a colorless and transparent liquid target product.

[0031]

The present invention is to produce a novel fluorine-containing carbonyl compound by using trifluorolactic acid ethyl ester and a Grignard reagent as starting materials and converting the ester into a ketone by a simple two-step reaction.

[0032]

EXAMPLES The present invention will be specifically described below based on Reference Examples and Examples.

Reference Example 1 [Production of trifluorolactic acid ethyl ester] In a three-necked round bottom flask equipped with a reflux condenser, a thermometer, and a stirrer, 14.4 g (100 mmol) of trifluorolactic acid was added.
300 ml of ethanol and 150 ml of concentrated sulfuric acid were added, and the mixture was heated under reflux with stirring. As a result of heating and refluxing for 10 hours while tracing the lactic acid peak by ¹⁹ F-NMR, it was confirmed that lactic acid in the reaction solution was lost. Then, the reaction solution was neutralized with a saturated aqueous solution of sodium hydrogen carbonate, and the aqueous solution was added until the pH reached 8-9. The obtained product was extracted with ether, anhydrous magnesium sulfate was added to the extract to remove water as hydrous magnesium sulfate, ether was distilled off under reduced pressure from the filtrate, and the remaining syrup-like substance was distilled under reduced pressure to obtain the desired product. I got a thing. The yield of product obtained is 15.
It was 5 g (90 mmol) and the yield was 90%.

The boiling point, nuclear magnetic resonance spectrum ( ¹ HNMR spectrum and ¹⁹ FNMR spectrum), infrared absorption spectrum (IR absorption spectrum) and mass spectrum [MS spectrum] of this product were measured to find that it was trifluorolactic acid ethyl ester. It was confirmed. Boiling point: 58 ° C / 28mmHg ¹ H NMR spectrum (CCl ₄ ): 1.33ppm (t, J = 7.0Hz, 3H): 4.31ppm (q, J = 7.0Hz, 2H): 4.42ppm (S, 1H): 4.50ppm (q, J = 7.0Hz, 1H) ¹⁹ FNMR spectrum (from ext. CF ₃ COOH): -2.50 ppm (d, J = 7.0Hz) IR absorption spectrum (neat): 3,480 cm ^-1 (OH): 1,750 cm ^-1 (CO) MS spectrum: m / z 172 (M ⁺ )

(Reference Example 2) [Production of ether solution of Grignard reagent] Under argon atmosphere, a mixture of 24 g (300 mmol) of magnesium (shavings) and 30 ml of ether was vigorously stirred, and n-hexyl = Bromide 9.9g
90 ml of an ether solution of (60 mmol) was added dropwise so that the reaction would continue, and after all was added, the mixture was refluxed for 30 minutes.
-Hexyl magnesium = bromide 56.7 g (300
(Mmol) of ether solution was obtained.

(Example) [1-Hydroxy-2,2,2]
-Production of trifluoroethylhexyl ketone] In a four-necked round bottom flask equipped with a reflux condenser, thermometer, stirrer, and funnel, 17.2 g (100 mmol) of an ether solution of trifluorolactic acid ethyl ester obtained in Reference Example 1 was added. Add 500 ml and immerse in a dry ice-acetone bath,
Cooled to -78 ° C with stirring. While stirring this solution, an ether solution 50 of 37.8 g (200 mmol) of n-hexylmagnesium bromide obtained in Reference Example 2 was added.
0 ml was added dropwise from the dropping funnel over 100 minutes, taking care not to raise the reaction temperature. After completion of dropping
After left to stir at −78 ° C. for 2 hours, the dry ice-acetone bath was removed, and the temperature was raised to room temperature over 1 hour with stirring. Then, 200 ml of 2N hydrochloric acid aqueous solution was added at room temperature for 3 hours.
The solution was added dropwise over 0 minutes, and after completion of the addition, the mixture was stirred for 30 minutes. The obtained reaction solution was extracted with ether, anhydrous magnesium sulfate was added to the extract solution to remove water as hydrous magnesium sulfate, and ether was distilled off from the filtrate under reduced pressure. The remaining syrup-like substance was subjected to column chromatography (packing). Agent: silica gel, eluent: hexane / chloroform = 3/1) for purification to obtain 12.7 g (60 mmol, 60% yield) of a colorless transparent liquid target product.

Nuclear magnetic resonance spectrum ( ¹ H
NMR spectrum and ¹⁹ F NMR spectrum), infrared absorption spectrum (IR absorption spectrum) and mass spectrum (MS spectrum) were measured and the results are as follows: 1-hydroxy-2,2,2-trifluoroethylhexyl ketone It was confirmed. Also, ¹
HNMR spectrum chart and IR absorption spectrum chart
They are shown in FIGS. 1 and 2, respectively. ¹ H NMR spectrum (CDCl ₃ ): 0.5 to 2.05 ppm (11H, m): 2.20 to 2.95 ppm (2H, m): 3.45 ppm (1H, q J = 6.8Hz): 3.72 to 4.50 ppm (1H, br) ¹⁹ FNMR spectrum (from ext. CF ₃ COOH): -2.17 ppm (q, J = 6.8Hz) IR absorption spectrum (neat): 3,510cm ^-1 (OH): 1,730cm ^-1 (CO) MS spectrum: m / z 212 (M ⁺ )

[0038]

INDUSTRIAL APPLICABILITY The present invention is used as an intermediate raw material such as a ferroelectric liquid crystal which is a raw material of an electronic device, or as a medicine,
A novel 1-hydroxy-2,2,2-trifluoroethylalkylketone that is useful as a building block agent that can introduce various functional groups into compounds used for agricultural chemicals and is easy to handle is called trifluorolactic acid ethyl ester. In addition, it is possible to industrially advantageously manufacture the starting material which is easily available.

[Brief description of drawings]

FIG. 1 shows 1-hydroxy-2, obtained in an example of the present invention.
^1- HNM of 2,2-trifluoroethyl alkyl ketone
It is an R spectrum figure.

FIG. 2 shows 1-hydroxy-2, which was obtained in the example of the present invention.
It is an IR absorption spectrum figure of 2,2-trifluoroethyl alkyl ketone.

[Procedure amendment]

[Submission date] January 28, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0008

[Correction method] Change

[Correction content]

In the compound represented by the formula (1) in the present invention (hereinafter also referred to as the compound of the present invention), the alkyl group represented by R in the formula is an alkyl group having 3 to 10 carbon atoms,
That is, n-propyl, n-butyl, n-pentyl,
Among them, n-hexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl are useful compounds, and R is a straight-chain alkyl group having 4 to 8 carbon atoms because of its ease of production. is there. Specific examples of the compound that can be advantageously produced in the present invention are 1-hydroxy-2,2,2-trifluoro.
Ethyl butyl ketone, 1-hydroxy-2,2,2-trifluoroethyl-pentyl ketone, 1-hydroxy -
2,2,2-trifluoroethyl hexyl ketone, 1-
Hydroxy-2,2,2-trifluoroethyl heptyl ketone, 1-hydroxy-2,2,2-trifluoro-et
It is chill octyl ketone.

Claims (1)

[Claims] 1. A trifluorolactic acid ethyl ester is reacted with a Grignard reagent represented by the formula (2).
Then, the reaction product is hydrolyzed with a mineral acid, and 1-hydroxy-2,2,2-represented by the formula (1) is shown.
Method for producing trifluoroethyl alkyl ketone. [Chemical 1] RMgBr (2) (In the formula, R is a linear alkyl group having 3 to 10 carbon atoms and corresponds to R in the formula (1).)