Method for producing fluorinated organic compound and fluorinating reagent

Abstract

Object: An object of the present invention is to provide a method for producing, with a high yield, a fluorinated organic compound, the fluorinated organic compound having not been produced with a sufficient yield by a conventional method for producing a fluorinated organic compound using a fluorinating agent containing IF.sub.5-pyridine-HF alone. Another object of the present invention is to provide a fluorinating reagent. Means for achieving the object: A method for producing a fluorinated organic compound comprising step A of fluorinating an organic compound by bringing the organic compound into contact with (1) IF.sub.5-pyridine-HF and (2) at least one additive selected from the group consisting of amine hydrogen fluorides, X.sup.aF (wherein X.sup.a represents hydrogen, potassium, sodium, or lithium), oxidizers, and reducing agents.

Claims

1. A method for producing a fluorinated organic compound comprising step A of fluorinating an organic compound by bringing the organic compound into contact with (1) IF.sub.5-pyridine-HF and (2) at least one additive selected from the group consisting of amine hydrogen fluorides, X.sup.aF (wherein X.sup.a represents hydrogen, potassium, sodium, or lithium), oxidizers, and reducing agents, wherein the amount of the IF.sub.5-pyridine-HF used in step A is in the range of 1 to 10 mol per mol of the organic compound, the reaction temperature of step A is in the range of −20 to 140° C., and the reaction time of step A is in the range of 0.5 to 48 hours.

2. The method according to claim 1, wherein the additive is Et.sub.3N-nHF (wherein n is a real number of 1 to 9).

3. A fluorinating reagent comprising (1) IF.sub.5-pyridine-HF and (2) at least one additive selected from the group consisting of amine hydrogen fluorides, X.sup.aF (wherein X.sup.a represents hydrogen, potassium, sodium, or lithium), oxidizers, and reducing agents.

4. The fluorinating reagent according to claim 3, wherein the additive is Et.sub.3N-nHF (wherein n is a real number of 1 to 9).

Description

DESCRIPTION OF EMBODIMENTS

(1) The present invention is detailed below with reference to the Examples; however, it is not limited to the Examples.

Example 1-1

(2) ##STR00010##

(3) In air, IF.sub.5-pyridine-HF (370 mg, 1.15 mmol) and Et.sub.3N-6HF (1.15 mmol) were added to methylene chloride (2 mL) in a Teflon (trade name) container, and compound 1a (O-(4-isopropyl phenyl)S-methyl dithiocarbonate) (0.5 mmol) was added thereto at room temperature, followed by stirring at 60° C. for six hours. The reaction mixture was added to water (20 mL), and extraction was performed using methylene chloride three times (20 mL×3). The organic layer was washed with a saturated sodium bicarbonate aqueous solution (20 mL) and a saturated sodium thiosulfate aqueous solution (20 mL), and then dried with magnesium sulfate. After condensation, product 2a (trifluoromethyl 4-isopropyl phenyl ether) was obtained by silica gel column chromatography (hexane ether) with a yield of 70%.

Example 1-2

(4) ##STR00011##

(5) In air, IF.sub.5-pyridine-HF (321 mg, 1.00 mmol) and Et.sub.3N-6HF (553 mg, 2.50 mmol) were added to methylene chloride (1 mL) in a Teflon (trade name) container, and compound 1a (O-(4-isopropyl phenyl)S-methyl dithiocarbonate) (0.5 mmol) was added thereto at room temperature, followed by stirring at 60° C. for nine hours. The reaction mixture was added to water (30 mL), and extraction was performed using methylene chloride three times (20 mL×3). The organic layer was washed with a saturated sodium bicarbonate aqueous solution (20 mL) and a saturated sodium thiosulfate aqueous solution (20 mL), and then dried with magnesium sulfate. After condensation, product 2a (trifluoromethyl 4-isopropyl phenyl ether) was obtained by silica gel column chromatography (hexane ether) with a yield of 74%.

Comparative Example 1

(6) In air, IF.sub.5-pyridine-HF (321 mg, 1.00 mmol) was added to methylene chloride (1 mL) in a Teflon (trade name) container, and compound 1 (0.5 mmol) was added thereto at room temperature, followed by stirring at 60° C. for nine hours. The reaction mixture was added to water (30 mL), and extraction was performed using methylene chloride three times (20 mL×3). The organic layer was washed with a saturated sodium bicarbonate aqueous solution (20 mL) and a saturated sodium thiosulfate aqueous solution (20 mL), and then dried with magnesium sulfate. After condensation, product 2 was obtained by silica gel column chromatography (hexane ether) with a yield of 4%.

(7) It is obvious from the comparison of Example 1-1 and Comparative Example 1 that the use of additive Et.sub.3N-6HF remarkably increased the yield of product 2 in Example 1-1.

Comparative Example 2

(8) In air, IF.sub.5 (1.00 mmol), pyridine-HF (pyridine 1.00 mmol, HF 7.00 mmol), and Et.sub.3N (1.00 mmol) were added to methylene chloride (1 mL) in a Teflon (trade name) container, and compound (0.5 mmol) was added thereto at room temperature, followed by stirring at 60° C. for nine hours. The reaction mixture was added to water (20 mL), and extraction was performed using methylene chloride three times (20 mL×3). The organic layer was washed with a saturated sodium bicarbonate aqueous solution (20 mL) and a saturated sodium thiosulfate aqueous solution (20 mL), and then dried with magnesium sulfate. After condensation, product 2 was obtained by silica gel column chromatography (hexane ether) with a yield of 41%.

(9) It is obvious from the comparison of Example 1-1 and Comparative Example 2 that although IF.sub.5, pyridine, HF, and triethylamine were used in Comparative Example 2 in the same molar ratio as in Example 1-1, and the same reaction temperature, reaction time, and purification method were employed, product 2 was not obtained with a sufficient yield. This indicates that product 2 was not obtained with a high yield merely by adding Et.sub.3N as an additive to the reaction system.

(10) TABLE-US-00001 TABLE 1             Fluorinating reagent Example 1-1 (IF.sub.5-Py-HF) + Yield 70% (Et.sub.3N—6HF) Comparative (IF.sub.5-Py-HF) Yield 4% Example 1 Comparative IF.sub.5 + Py + Yield 41% Example 2 7HF + Et.sub.3N

Example 2

(11) Products were synthesized in the same manner as in Example 1, except that the substrate (compound 1a), reaction temperature, time, and solvent used in Example 1-1 were changed to those shown in Table 2.

(12) Regarding the “yield/%” in Table 2, the .sup.19F-NMR yield is based on the substrate. The value in parenthesis is an isolation yield.

(13) TABLE-US-00002 TABLE 2 Temperature/ Time/ Yield/ Substrate ° C. h Solvent Product % 60 24 (CH.sub.2Cl).sub.2 70 60 24 (CH.sub.2Cl).sub.2  65(55) r.t.  2 CH.sub.2Cl.sub.2  93(91) r.t.  3 CH.sub.2Cl.sub.2 0 100(67)  0 24 CH.sub.2Cl.sub.2 (70)

Example 3s

(14) Polyfluorination Reaction of Alkyl Sulfide

(15) ##STR00023##

(16) IF.sub.5-pyridine-HF (321 mg, 1 mmol) and dichloroethane (2.0 mL) were added to a Teflon (trade name) reaction vessel with a lid. Three drops of Et.sub.3N-7HF (54 mg, 0.22 mmol) were added thereto at room temperature. Subsequently, substrate 3 (122 mg, 0.5 mmol) was added thereto, followed by reaction at 80° C. for 14 hours. The reaction mixture was poured into water (30 mL) in a polycontainer, and neutralized with saturated NaHCO.sub.3 water, followed by ether extraction. After dehydration with magnesium sulfate, the solvent was removed under reduced pressure. An internal standard (monofluorobenzene) was added to the residue, and the product was quantified by .sup.19F-NMR. The results indicate that trifluoro body 4 was produced with a yield of 63%.

Example 4

(17) Addition to Alkene (1)

(18) ##STR00024##

(19) A substrate (alkene 5a, 0.5 mmol), methylene chloride (3 mL), and IF.sub.5-pyridine-HF (161 mg, 0.5 mmol) were added to a Teflon (trade name) container, and KI (83 mg, 0.5 mmol) was added thereto while stirring the mixture at 0° C. The mixture was then stirred at 0° C. for 30 minutes, and at room temperature for 17 hours. After the reaction, product 6a was extracted with methylene chloride, and purified by silica gel column chromatography (ethyl acetate-hexane) to obtain product 6a with a yield of 78%.

Example 5

(20) Addition to Alkene (2)

(21) ##STR00025##

(22) A substrate (alkene 5b, 0.5 mmol), methylene chloride (3 mL), and IF.sub.5-pyridine-HF (161 mg, 0.5 mmol) were added to a Teflon (trade name) container, and KI (83 mg, 0.5 mmol) was added thereto while stirring the mixture at 0° C. The mixture was then stirred at 0° C. for 30 minutes, and at room temperature for 17 hours. After the reaction, product 6b was extracted with methylene chloride, and purified by silica gel column chromatography (ethyl acetate-hexane) to obtain product 6b with a yield of 60%. The .sup.19F-NMR yield was 90%.

Example 6

(23) Addition to Alkyne

(24) ##STR00026##

(25) Alkyne 7 (0.5 mmol), IF.sub.5-pyridine-HF (1.0 mmol, 320 mg), and dichloroethane (5 mL) were added to a Teflon (trade name) container, and the mixture was stirred at 0° C. for 20 minutes. An additive shown in Table 3 (hydroquinone (1.0 mmol, 110 mg) or catechol (1.0 mmol, 110 mg) was added thereto, and the mixture was further stirred at 0° C. for 30 minutes, and at room temperature for 12 hours. After extraction with dichloroethane, isolation and purification was performed by silica gel column chromatography (ethyl acetate-hexane). Table 3 shows the yield of product 8.

(26) In Table 3, regarding the “yield/%,” the .sup.19F-NMR yield was based on the substrate. The value in parenthesis is the isolation yield.

(27) TABLE-US-00003 TABLE 3 8 Additive Yield/% Hydroquinone 82 (63) Catechol 75

Example 7

(28) Products were synthesized in the same manner as in Example 6, except that the substrate (compound 7), amount of IF.sub.5-pyridine-HF, additive, time, and reaction solvent used in Example 6 were changed to those shown in Table 4.

(29) Regarding the “yield/%” in Table 4, the .sup.19F-NMR yield is based on the substrate. The value in parenthesis is an isolation yield.

(30) TABLE-US-00004 TABLE 4 Time/ Yield/ Substrate IF.sub.5-pyridine-HF Additive h Solvent Product % Ph—≡—H 7b 1.5 eq. Hydroquinone 1.5 eq. 9 CH.sub.2Cl.sub.2 56 Ph—≡—Ph 7c 2.0 eq. Hydroquinone 2.0 eq. 15 CH.sub.2Cl.sub.2 90(72) Pr—≡—Pr 7d 2.0 eq. Hydroquinone 2.0 eq. 15 CH.sub.2Cl.sub.2 87 0 2.0 eq. Hydroquinone 2.0 eq. 19 CH.sub.2Cl.sub.2 73 2.0 eq. Hydroquinone 2.0 eq. 20 CH.sub.2Cl.sub.2 72 2.0 eq. Hydroquinone 2.0 eq. 20 CH.sub.2Cl.sub.2 67