Fluorinating agent

Abstract

An object of the present invention is to provide a novel substance that has a high reactivity as a fluorinating agent, is effectively used in various fluorination reactions, and is safely handled even in air. As the solution for achieving this object, the present invention provides a complex obtained by reacting bromine trifluoride with at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals in a nonpolar solvent. This complex serves as a fluorinating agent that provides excellent fluorination performance and that is stable in air.

Claims

1. A method for fluorinating a compound, the method comprising: bringing the compound into contact with a complex consisting of bromine trifluoride and at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals.

2. The method according to claim 1, wherein the complex exhibits an exothermic decomposition onset temperature in nitrogen of 40 C. or higher.

3. The method according to claim 1, wherein the complex is a reaction product obtained by mixing bromine trifluoride with at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals, in a nonpolar solvent.

4. The method according to claim 3, wherein the reaction product is obtained by reacting 0.5 mol or more of the metal halide, per mol of bromine trifluoride.

5. The method according to claim 1, wherein the metal halide is at least one member selected from the group consisting of a halogenated metal represented by the formula: MX, wherein M is M.sup.1 or (M.sup.2).sub.1/2), M.sup.1 is an alkali metal, and M.sup.2 is an alkaline earth metal, and X is a halogen atom; and a halogenated metal represented by the formula: MHX.sup.2, wherein M and X are as defined above.

6. The method according to claim 1, wherein the metal halide is at least one potassium halide selected from the group consisting of halogenated potassium and halogenated hydrogen potassium.

7. The method according to claim 1, wherein the metal halide is at least one potassium fluoride selected from the group consisting of fluorinated potassium and fluorinated hydrogen potassium.

Description

DESCRIPTION OF EMBODIMENTS

(1) The following describes the present invention in more detail with reference to Examples. The symbols and abbreviations used in the Examples are as they are usually used in the chemical field, unless otherwise stated.

Example 1 (Production of Complex)

(2) KHF.sub.2 (5.17 g, 66 mmol) and CH.sub.2Cl.sub.2 (30 mL) were placed in a Teflon (registered trademark) container, and cooled to 78 C., followed by dropwise addition of BrF.sub.3 (4.54 g, 33 mmol). While the temperature was maintained, the mixture was stirred for 30 minutes, and the temperature was increased to room temperature. The liquid portion was removed, and the solid portion was washed by adding 20 mL of CH.sub.2Cl.sub.2, the procedure of which was repeated three times. The resulting product was then stirred while nitrogen was blown in to obtain a complex (BrF.sub.3-2KHF.sub.2 complex) (8.84 g, 91%) as a solid by reacting 2 mol of KHF.sub.2, per mol of BrF.sub.3.

(3) .sup.19F-NMR (30 KHz) 10-65 (m), 150 (s).

(4) The obtained complex was mixed with methylene chloride at room temperature; however, an exothermic phenomenon was not observed, and no reaction occurred. The exothermic decomposition onset temperature in nitrogen of the complex was measured by the method described above and was 197 C.

Example 2 (Production of Complex)

(5) KF (2.5 g, 44 mmol) and CH.sub.2Cl.sub.2 (10 mL) were placed in a Teflon (registered trademark) container and cooled to 78 C., followed by dropwise addition of BrF.sub.3 (3.0 g, 22 mmol). While the temperature was maintained, the mixture was stirred for 30 minutes, and the temperature was increased to room temperature. The liquid portion was removed, and the solid portion was washed by adding 5 mL of CH.sub.2Cl.sub.2, the procedure of which was repeated three times. The resulting product was then stirred while nitrogen was blown in to obtain a complex (BrF.sub.3-2KF complex) as a solid by reacting 2 mol of KF, per mol of BrF.sub.3.

(6) .sup.19F-NMR (30 KHz) 133 (s), 150 (s).

(7) The obtained complex was mixed with methylene chloride at room temperature; however, an exothermic phenomenon was not observed, and no reaction occurred. The exothermic decomposition onset temperature in nitrogen of the complex was measured by the method described above and was 252 C.

Example 3 (Desulfurization-Difluorination Reaction)

(8) The BrF.sub.3-2KHF.sub.2 complex (193 mg, 0.66 mmol) obtained in Example 1 and CH.sub.2Cl.sub.2 (2.4 mL) were placed in a Teflon (registered trademark) container. Then, compound 1a (100 mg, 0.3 mmol) shown in Table 1 below was added thereto at room temperature and stirred for 1 hour while the temperature was maintained. After the completion of the reaction, the resulting product was quenched with the addition of water, and after separation, the washing was performed with a saturated aqueous NaHCO.sub.3 solution and a saturated aqueous Na.sub.2S.sub.2O.sub.3 solution. The organic layer was dried over MgSO.sub.4 and concentrated, followed by purification by silica column chromatography. In this manner, compound 2a (57 mg, 84%) shown in Table 1 below was obtained.

Examples 4 to 6 (Desulfurization-Difluorination Reaction)

(9) The desulfurization-difluorination reaction was performed as in Example 3, except that compounds 1b to 1d shown in Table 1 below were used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 1. Table 1 shows the resulting products and their yields. In each table below, the values shown in the Yield columns are isolated yields, and the values in parentheses are yields calculated from F-NMR.

(10) TABLE-US-00001 TABLE 1 Molar ratio of fluorinating agent (to starting Reaction Ex. Starting material material) time Product Yield (%) 3 2.2 1 h 84 4 0 3.0 15 min 76 (85) 5 3.0 15 min 91 (99) 6 2.2 3 h (92)

Example 7 (Desulfurization-Difluorination Reaction)

(11) The desulfurization-difluorination reaction was performed as in Example 3, except that compound 1e shown in Table 2 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 2. Table 2 shows the resulting product and the yield.

(12) TABLE-US-00002 TABLE 2 Molar ratio of fluorinating agent (to starting Reaction Yield Ex. Starting material material) time Product (%) 7 3.0 3.5 h (80)

Examples 8 and 9 (Desulfurization-Fluorination Reaction)

(13) The desulfurization-fluorination reaction was performed as in Example 3, except that compound 1f or 1g shown in Table 3 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material, the reaction temperature, and the reaction time were changed to the values shown in Table 3. Table 3 shows the resulting products and their yields.

(14) TABLE-US-00003 TABLE 3 Molar ratio of fluorinating agent (to starting Reaction Ex. Starting material material) conditions Product Yield (%) 8 3.1 0 C., 1 h 81 9 0 3.2 0 C., 15 min 52 (62)

Examples 10 and 11 (Desulfurization-Fluorination Reaction)

(15) The desulfurization-fluorination reaction was performed as in Example 3, except that compound 1h or 1i shown in Table 4 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 4. Table 4 shows the resulting products and their yields.

(16) TABLE-US-00004 TABLE 4 Molar ratio of fluorinating agent (to starting Reaction Yield Ex. Starting material material) conditions Product (%) 10 2.2 Room temperature, 45 min 81 (90) 11 3.2 Room temperature, 45 min (84)

Example 12 (Desulfurization-Fluorination Reaction)

(17) The desulfurization fluorination reaction was performed as in Example 3, except that compound 1j shown in Table 5 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 5. The resulting product and the yield are shown in Table 5. The yield of the -form was 52% while the yield of the -form was 31%, and the total yield of both was 83%.

Example 12-2 (Desulfurization-Fluorination Reaction)

(18) The desulfurization fluorination reaction was performed as in Example 3, except that compound 1j-2 shown in Table 5 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 5. The resulting product and the yield are shown in Table 5. The yield of the -form was 52% while the yield of the -form was 31%, and total yield of both was 83%.

(19) TABLE-US-00005 TABLE 5 Molar ratio of fluorinating agent Starting (to starting Reaction Yield Ex. material material) conditions Product (%) 12 1.5 4 h 83 (86) (: = 52:31) 12-2 1.5 4 h 83 (86) (: = 52:31)

Example 13 (Denitrification-Fluorination Reaction)

(20) The desulfurization-fluorination reaction was performed as in Example 3, except that compound 1k shown in Table 6 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 6. Table 6 shows the resulting product and the yield.

(21) TABLE-US-00006 TABLE 6 Molar ratio of fluorinating agent Starting (to starting Reaction Yield Ex. material material) time Product (%) 13 0 2.2 3.5 h 54 (73)

Example 14 (Addition of BrF to Olefin)

(22) The BrF.sub.3-2(KHF.sub.2) complex (293 mg, 1 mmol) obtained in Example 1 and CH.sub.2Cl.sub.2 (5 mL) were placed in a Teflon (registered trademark) container. Then, compound 1l (68 mg, 0.5 mmol) shown in Table 7 below was added thereto at 40 C. and stirred for 24 hour while the temperature was maintained. After the completion of the reaction, the resulting product was quenched with the addition of water, and after separation, the washing was performed with a saturated aqueous NaHCO.sub.3 solution and a saturated aqueous Na.sub.2S.sub.2O.sub.3 solution. The organic layer was dried over MgSO.sub.4 and concentrated, followed by purification by silica column chromatography. In this manner, compound 2l (58 mg, 50%) was obtained.

(23) TABLE-US-00007 TABLE 7 Molar ratio of fluorinating agent Starting (to starting Reaction Yield Ex. material material) conditions Product (%) 14 2.0 40 C., 24 h 50

Example 15 (Desulfurization-Difluorination Reaction)

(24) The desulfurization-difluorination reaction was performed as in Example 3, except that compound 1m shown in Table 8 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material and the reaction time were changed to the values shown in Table 8. Table 8 shows the resulting product and the yield.

(25) In the structural formula of compound 1m, Ar represents p-chlorophenyl.

(26) TABLE-US-00008 TABLE 8 Molar ratio of fluori- nating agent (to Re- starting action Yield Ex. Starting material material) time Product (%) 15 2.0 3 h (84)

Examples 16 to 18 (Desulfurization-Fluorination Reaction)

(27) The desulfurization fluorination reaction was performed as in Example 3, except that compounds 1o to 1q shown in Table 9 below were used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material, the reaction temperature, and the reaction time were changed to the values shown in Table 9. Table 9 shows the resulting products and their yields.

(28) TABLE-US-00009 TABLE 9 Molar ratio of fluorinating agent (to starting Reaction Yield Ex. Starting material material) conditions Product (%) 16 2.2 Room temperature, 45 min (91) 17 2.2 Room temperature, 15 min 91(99) 18 0 2.2 0 C., 60 min (81)

Examples 19 to 21 (Desulfurization-Fluorination Reaction)

(29) The desulfurization-fluorination reaction was performed as in Example 3, except that compounds 1r to 1t shown in Table 10 below were used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material, the reaction temperature, and the reaction time were changed to the values shown in Table 10. Table 10 shows the resulting products and their yields.

(30) TABLE-US-00010 TABLE 10 Molar ratio of fluorinat- ing agent (to starting Reaction Yield Ex. Starting material material) conditions Product (%) 19 1.1 0 C., 15 min 89 (94) 20 1.1 Room temperature, 15 min 87 21 1.1 Room temperature, 15 min (66)

Example 22 (Desulfurization-Fluorination Reaction)

(31) The desulfurization fluorination reaction was performed as in Example 3, except that compound 1u shown in Table 11 below was used as the starting material in place of compound 1a used in Example 3, and that the molar ratio of the fluorinating agent to the starting material, the reaction temperature, and the reaction time were changed to the values shown in Table 11. Table 11 shows the resulting product and the yield.

(32) TABLE-US-00011 TABLE 11 Molar ratio of fluorinating agent (to starting Reaction Yield Ex. Starting material material) conditions Product (%) 23 3.2 0 C., 15 min 76 (83)