JPH08333358A - Perfluoro(2-methyl-1,2-epoxypropyl) ether compound and its production - Google Patents

Abstract

PURPOSE: To obtain the subject compound useful as a synthetic raw material for a medicine, an agrochemical, a liquid crystal, etc., or a synthetic intermediate for an α-(trifluoromethyl)arylacetic acid as an optically active purity determining reagent, etc. CONSTITUTION: This perfluoro(2-methyl-1,2-epoxypropyl) ether compound is shown by the formula (R is a lower alkyl, an aryl or benzyl) such as perfluoro(2- methyl-1,2-epoxypropyl) methyl ether. The compound shown by the formula, for example, is obtained by oxidizing heptafluoroisobutenyl ether compound of the formula (CF3 )2 C=CF(OR) with ozone. The epoxy group of the compound of the formula is readily cleft in the presence or absence of a catalyst, is reacted with an aromatic compound to form an α,α-bis(trifluoromethyl)arylacetic aid ester and then to form a carboxylic acid salt by action of a base and water. The carboxylic acid salt is decarboxylated and hydrolyzed to give an α-(trifluoromethyl)arylacetic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a perfluoro (2-methyl-1,2-epoxypropyl) ether compound and a process for producing the same. More specifically, it relates to a perfluoro (2-methyl-1,2-epoxypropyl) ether compound effectively used as a synthetic intermediate of α- (trifluoromethyl) arylacetic acid and a method for producing the same.

[0002]

PRIOR ART General formula The α- (trifluoromethyl) arylacetic acid represented by is used as a raw material for producing pharmaceuticals, agricultural chemicals, liquid crystals, etc., or as a reagent for determining optical purity.

It has been conventionally proposed to produce α- (trifluoromethyl) arylacetic acid having such various uses by the following method. (1) Journal of Organic Chemistry, 32, 2797 (196
7)

(2) Journal of Fluorine Chemistry, 22
Volume, 561 (1983)

(3) Journal of Organic Chemistry, 49
Volume, 3702 (1984)

(4) Synthesis, 10 volumes, 965 pages (1992)

[0007] However, each of these methods has drawbacks such as expensive raw materials, multiple steps of synthesis steps, and inability to synthesize a large amount, all of which are economically advantageous methods. Not really.

[0008]

The object of the present invention is to easily produce α- (trifluoromethyl) arylacetic acid, which is used as a raw material for producing pharmaceuticals, agricultural chemicals, liquid crystals, etc., or as an optical purity determining reagent, etc. It is to provide a compound useful as an intermediate and a method for producing the same.

[0009]

According to the present invention, the general formula (Wherein R is a lower alkyl group, an aryl group or a benzyl group) represented by perfluoro (2-methyl-1,2-
Epoxypropyl) ether compounds are provided.

Such a perfluoro (2-methyl-1,2-epoxypropyl) ether compound has the general formula (CF ₃ ) ₂ C═CF (O
It is produced by ozone-oxidizing a heptafluoroisobutenyl ether compound represented by R).

The heptafluoroisobutenyl ether compound used as a raw material is an addition reaction product obtained by addition-reacting octafluoroisobutene (CF ₃ ) ₂ C = CF ₂ with a lower alcohol, phenol, benzyl alcohol or the like.
It can be easily obtained by subjecting (CF ₃ ) ₂ CHCF ₂ OR to a dehydrofluorination reaction using potassium hydroxide or the like.

For the ozone oxidation reaction of the heptafluoroisobutenyl ether compound, a glass reaction vessel or the like is used.
After charging the raw material there, in the absence of a solvent or in the presence of a solvent such as hydrocarbons, halogenated hydrocarbons, ethers, water, ozone-containing oxygen gas or air at about -70 ~ under stirring conditions. It is carried out by contacting at a temperature of 110 ° C, preferably about -40 to 60 ° C. The ozone concentration in oxygen gas or air is not particularly limited, but is generally about 0.
It is used in an amount of 1 to 1000 mg / L, preferably about 1 to 500 mg / L, and a molar ratio of ozone to the raw material of about 1.

The reaction product, perfluoro (2-methyl-1,
The structure of the 2-epoxypropyl) ether compound can be confirmed by the following means. (a) Characteristic absorption at a wave number of 1230 cm ^-1 derived from oxirane ring in infrared absorption spectrum (b) Bonding mode of fluorine atom by ¹⁹ F-NMR (c) Bonding mode of hydrogen atom by ¹ H-NMR (d) Mass Characteristic strong peak derived from spectrum (M / Z) = 228

The epoxy group contained in the obtained perfluoro (2-methyl-1,2-epoxypropyl) ether compound is
It has a very high activity and is easily cleaved in the presence or absence of a catalyst to react with an aromatic compound (ArH) to form an α, α-bis (trifluoromethyl) aryl acetic acid ester. , It is converted to the corresponding carboxylate salt by the action of base and water, which is decarboxylated to form an olefinic compound, which is further hydrolyzed to form α- (trifluoromethyl) arylacetic acid. .

[0015]

EFFECTS OF THE INVENTION By oxidizing a heptafluoroisobutenyl ether compound with ozone, perfluoro is easily
A (2-methyl-1,2-epoxypropyl) ether compound can be obtained. This compound is reacted with an aromatic compound to obtain α, α-bis (trifluoromethyl) aryl acetic acid ester, and then α- (is used by a very general reaction means such as hydrolysis, decarboxylation and hydrolysis. Trifluoromethyl) aryl acetic acid can be prepared.

[0016]

EXAMPLES The present invention will now be described with reference to examples.

Example A three-necked flask having a capacity of 300 ml equipped with a Dimroth condenser, a stirrer and a gas introduction tube was charged with 200 g (0.88 mol) of heptafluoroisobutenyl methyl ether (purity 93%), and the Dimroth condenser was equipped with Flow the brine at -20 ° C, then 0 ° C
While agitating, oxygen gas having an ozone concentration of 125 mg / L was bubbled for about 11 hours and 18 minutes at about 340 L (ozone amount of about 0.88 mol). After the reaction was completed, 134.8 g of a reaction product was taken out and distilled, and 73.0 g of perfluoro (2-methyl-1,2-epoxypropyl) methyl ether was obtained as a fraction having a boiling point of 82 to 85 ° C (yield 36.5%). %)Obtained. Infrared absorption spectrum: 1230 cm ^-1 (oxirane ring) ¹⁹ F-NMR (TFA, CH ₂ Cl ₂ ): -15.3ppm (d, J = 2.19Hz, 1F) + 0.58ppm (dq, J = 2.19, 2.63Hz, 3F) + 1.90ppm (q, J = 2.
63Hz, 3F) ¹ H-NMR (TMS, CDCl ₃ ): 3.58ppm (s, 3H)

Reference Example 1 A three-necked flask having a capacity of 100 ml equipped with a stirrer and a dropping funnel was charged with 6.67 g of anhydrous aluminum chloride and 50 ml of dry benzene, the flask was cooled to 0 ° C., and 30 ml of dry benzene was stirred therein. Diluted with perfluoro (2
-Methyl-1,2-epoxypropyl) methyl ether 11.4 g
(0.05 mol) was added dropwise. After stirring and reacting at room temperature for 10 hours, the reaction mixture was poured into ice water, and the separated organic layer was dried over anhydrous MgSO ₄ . The aqueous layer was extracted with dichloromethane, and the extract was dried over anhydrous MgSO ₄ . After these two organic layers were combined and concentrated, the residue was distilled under a reduced pressure of 15 mmHg at a bath temperature of 120 to 130 ° C. to give 10.05 g of α, α-bis (trifluoromethyl) phenylacetic acid methyl ester (yield 70 %)Obtained. Infrared absorption spectrum: 1810 cm ^-1 (C = O) ¹⁹ F-NMR (TFA, CH ₂ Cl ₂ ): + 4.1ppm (s) ¹ H-NMR (TMS, CDCl ₃ ): 3.7ppm (s, 3H) 7.1 ppm (m, 5H)

Reference Example 2 A three-necked flask having a capacity of 50 ml equipped with a stirrer and a dropping funnel was charged with 2.67 g of anhydrous aluminum chloride and 10 ml of dry isobutylbenzene, the flask was cooled to 0 ° C., and dried while stirring. 4.56 g (0.02 mol) of perfluoro (2-methyl-1,2-epoxypropyl) methyl ether diluted with 2 ml of benzene was added dropwise. After stirring and reacting at room temperature for 10 hours, the reaction mixture was poured into ice water, and the separated organic layer was dried over anhydrous MgSO ₄ . The aqueous layer was extracted with dichloromethane, and the extract was dried over anhydrous MgSO ₄ . After combining and concentrating the two organic layers, the residue (1
0.98 g) was distilled under a reduced pressure of 5 mmHg at a bath temperature of 40 to 120 ° C., and the fraction was subjected to silica gel column chromatography using n-hexane as a mobile phase to obtain α, α-bis (trifluoromethyl) -p- 4.05 g of isobutylphenylacetic acid methyl ester
(Yield 59%) was obtained. Infrared absorption spectrum: 1790 cm ^-1 (C = O) ¹⁹ F-NMR (TFA, CH ₂ Cl ₂ ): -3.2 ppm (s) ¹ H-NMR (TMS, CDCl ₃ ): 0.87 ppm (d, J = 7.2) Hz, 6H) 1.35 ~ 2.34ppm (m, 1H) 2.43ppm (d, J = 6.3Hz, 2H) 3.81ppm (s, 3H) 7.02ppm (s, 4H)

Reference Example 3 In a three-necked flask having a capacity of 100 ml equipped with a stirrer and a dropping funnel, 1.28 g (0.01 mol) of naphthalene, 50 ml of dry dichloromethane and 2.28 of perfluoro (2-methyl-1,2-epoxypropyl) methyl ether. g (0.01 mol) was charged, the flask was cooled to 0 ° C, and while stirring, BF ₃ · Et ₂ O was added thereto.
1.23 ml was added. After reacting by stirring at 45 ° C for 24 hours,
The reaction mixture was poured into ice water and the separated organic layer was washed with anhydrous MgSO 4.
Dried at ₄ . The aqueous layer was extracted with dichloromethane, and the extract was dried over anhydrous MgSO ₄ . After combining and concentrating these two organic layers, the residue (2.86 g) was heated to a bath temperature of 60 mm under a reduced pressure of 20 mmHg.
Sublimation was performed at ~ 120 ° C to obtain 1.47 g of a sublimate. This was subjected to silica gel column chromatography using n-hexane / dichloromethane as a mobile phase to give 0.84 g of α, α-bis (trifluoromethyl) naphthylacetic acid methyl ester (yield 25
%)Obtained. Infrared absorption spectrum: 1800 cm ^-1 (C = O) ¹⁹ F-NMR (TFA, CH ₂ Cl ₂ ): -5.3 ppm (s) ¹ H-NMR (TMS, CDCl ₃ ): 3.82 ppm (s, 3H) 6.90 ~ 8.20ppm (m, 7H)

Reference Example 4 A 3-necked flask having a capacity of 10 ml equipped with a stirrer and a dropping funnel was charged with 0.67 g (0.01 mol) of pyrrole, and the flask was cooled to 0.
After cooling to ℃ and stirring, 2.28 g of perfluoro (2-methyl-1,2-epoxypropyl) methyl ether (0.01
Mol) was added dropwise. After completion of dropping, dichloromethane and water were added and stirred, the aqueous layer was neutralized as it was with sodium hydrogen carbonate, and the separated organic layer was dried over anhydrous MgSO ₄ . After the two organic layers were combined and concentrated, the residue (0.97 g) was n-
Silica gel column chromatography using hexane as a mobile phase gave 0.3 g (yield 10%) of α, α-bis (trifluoromethyl) -2-pyrrolyl acetic acid methyl ester. Infrared absorption spectrum: 1740cm ^-1 (C = O) 3435cm ^-1 (NH) ¹⁹ F-NMR (TFA, CH ₂ Cl ₂ ): -1.0ppm (s) ¹ H-NMR (TMS, CDCl ₃ ): 3.46ppm (s, 3H) 6.05 to 7.14ppm (m, 3H) 7.76 to 9.34ppm (br, 1H)

Reference Example 5 In an eggplant-shaped flask having a capacity of 100 ml equipped with a Marine type cooling tube, 2.9 g (10 mmol) of α, α-bis (trifluoromethyl) phenylacetic acid methyl ester and 2.5 g of sodium hydroxide (63
(Mmol), 3.0 g of water and 3.0 ml of methanol were charged, and 90
Reflux for 6 hours at a bath temperature of ° C. Methanol was distilled off from the reaction mixture under reduced pressure, 30 ml of 3N hydrochloric acid was added to the residue to dissolve it, and the mixture was extracted with ether. The ether layer was dried over anhydrous MgSO _4.
After drying at 50 ° C. and concentration under reduced pressure, the residue was subjected to silica gel column chromatography using n-hexane / dichloromethane as a mobile phase to remove α- (trifluoromethyl) phenylacetic acid.
1.26 g (yield 62%) was obtained. Infrared absorption ^{spectrum: 3210cm -1 (OH) 1720cm -1} (C = O) 19 F-NMR (TFA, CH 2 Cl 2): - 1.29ppm (d, J = 7.6Hz) 1 H-NMR (TMS, CDCl ₃ ): 4.26ppm (q, 1H, J = 7.2Hz, methine-H) 7.28ppm (s, 5H, ph) 11.9ppm (br, 1H, OH)

Claims (2)

[Claims] 1. A general formula (Wherein R is a lower alkyl group, an aryl group or a benzyl group) represented by perfluoro (2-methyl-1,2-
Epoxypropyl) ether compound. 2. The general formula (CF ₃ ) ₂ C═CF (OR) (wherein R is a lower alkyl group, an aryl group or a benzyl group).
The heptafluoroisobutenyl ether compound represented by (Wherein R is the same as defined above), and a method for producing a perfluoro (2-methyl-1,2-epoxypropyl) ether compound.