Fluorinated organic compound production method

Abstract

An object of the present invention is to provide a method for producing a fluorinated organic compound, whereby an iodosylbenzene derivative can be easily separated and recovered. The above object can be achieved by a method for producing a fluorinated organic compound, comprising step A of fluorinating an organic compound (1) by reaction with a fluorine source (3) in the presence of a hypervalent iodine aromatic ring compound (2a), or in the presence of an iodine aromatic ring compound (2b) and an oxidant (2bo); wherein the fluorine source (3) is a fluorine source (3a) represented by formula: MF.sub.n, wherein M is H, a metal of Group 1 of the periodic table, or a metal of Group 2 of the periodic table; and n is 1 or 2; and step B of separating the iodine aromatic ring compound from a reaction liquid after step A is started.

Claims

1. A method for producing a fluorinated organic compound, comprising: step A of fluorinating an organic compound (1) by reaction with a fluorine source (3) in the presence of a hypervalent iodine aromatic ring compound (2a), or in the presence of an iodine aromatic ring compound (2b) and an oxidant (2bo); wherein the fluorine source (3) is a fluorine source (3a) represented by formula: MF.sub.n, wherein M is H, a metal of Group 1 of the periodic table, or a metal of Group 2 of the periodic table; and n is 1 or 2; step B of separating the iodine aromatic ring compound from a reaction liquid after step A is started; and step C of oxidizing the iodine-substituted aromatic ring compound separated from the reaction liquid in step B with an oxidant (C), wherein the organic compound (1) is: an organic compound represented by formula (1a): ##STR00014## wherein A is a hydrogen atom, an aromatic group optionally having one or more substituents, an alkyl group optionally having one or more substituents, a halogen atom, —OR, or —NR.sub.2, R.sup.1 is a hydrogen atom, an organic group, or a halogen atom, R.sup.2 is a hydrogen atom, an organic group, or a halogen atom, and R is independently at each occurrence a hydrogen atom or an organic group; or an organic compound represented by formula (1b): ##STR00015## wherein R.sup.3 is a hydrogen atom, an aromatic group optionally having one or more substituents, an alkyl group optionally having one or more substituents, a halogen atom, —OR, or —NR.sub.2, R.sup.4 is a hydrogen atom, an aromatic group optionally having one or more substituents, an alkyl group optionally having one or more substituents, a halogen atom, —OR, or —NR.sub.2, R.sup.5 is a hydrogen atom, an aromatic group optionally having one or more substituents, an alkyl group optionally having one or more substituents, a halogen atom, —OR, or —NR.sub.2, and R is independently at each occurrence a hydrogen atom or an organic group; and wherein the hypervalent iodine aromatic ring compound (2a) is an organic compound represented by formula (2a1): ##STR00016## wherein Ar is an aromatic ring, R.sup.p1 is independently at each occurrence a group: —O—(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a group: —(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a group: —O—(CH.sub.2).sub.q-A, wherein q is a number greater than or equal to 1; A is —SO.sub.3Y or —COOY; Y is independently at each occurrence H, a metal atom, or NR.sup.5.sub.4; and R.sup.5 is independently at each occurrence H or an organic group, a group: —(CH.sub.2).sub.q-A, wherein q is a number greater than or equal to 1; A is —SO.sub.3Y or —COOY; Y is independently at each occurrence H, a metal atom, or NR.sup.5.sub.4; and R.sup.5 is independently at each occurrence H or an organic group, a carboxylic acid group, or a sulfonic acid group; R.sup.p2 is independently at each occurrence an alkyl group, an alkoxy group, a group: —O—(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a group: —(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a halogen atom, a cyano group, a nitro group, a carboxylic acid group, a sulfonic acid group, a hydroxy group, or a phosphoryloxy group; or two R.sup.p2 bonded to one iodine atom optionally together form ═O; n1 is a number greater than or equal to 1; n2 is a number greater than or equal to 1; and the sum of n1 and n2 is in the range of 2 to 11; and the iodine aromatic ring compound (2b) is an organic compound represented by formula (2b1): ##STR00017## wherein Ar is an aromatic ring; R.sup.p1 is independently at each occurrence a group: —O—(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a group: —(CH.sub.2).sub.q—NR.sub.3X, wherein q is a number greater than or equal to 1; R is H or a C.sub.1-C.sub.20 alkyl group; and X is a halogen atom, an arylsulfonyloxy group, or an alkylsulfonyloxy group, a group: —O—(CH.sub.2).sub.q-A, wherein q is a number greater than or equal to 1; A is —SO.sub.3Y or —COOY; Y is independently at each occurrence H, a metal atom, or NR.sup.5.sub.4; and R.sup.5 is independently at each occurrence H or an organic group, a group: —(CH.sub.2).sub.q-A, wherein q is a number greater than or equal to 1; A is —SO.sub.3Y or —COOY; Y is independently at each occurrence H, a metal atom, or NR.sup.5.sub.4; and R.sup.5 is independently at each occurrence H or an organic group, a carboxylic acid group, or a sulfonic acid group; n1 is a number greater than or equal to 1; n2 is a number greater than or equal to 1; and the sum of n1 and n2 is in the range of 2 to 11.

2. The production method according to claim 1, wherein R.sup.p1 in formulas (2a1) and (2b1) is independently at each occurrence a carboxylic acid group, or a sulfonic acid group.

3. The production method according to claim 1, wherein R.sup.p2 in formula (2a1) is independently at each occurrence a halogen atom, an acetic acid group, a trifluoroacetic acid group, a tosic acid group, a hydroxy group, a phosphoryloxy group, a trifluoromethanesulfonic acid group, a propionic acid group, a 3,3,3-trifluoropropionic acid group, a perfluoropropionic acid group, a perfluorobutyric acid group, or a methanesulfonic acid group.

4. The production method according to claim 1, wherein the oxidant (2bo) is one or more members selected from the group consisting of metachloroperbenzoic acid, hydrogen peroxide, peracetic acid, perbenzoic acid, tert-butyl hydroperoxide, cumene hydroperoxide, potassium persulfate, and a potassium hydrogen persulfate-potassium hydrogen sulfate-potassium sulfate mixture.

5. The method according to claim 1, wherein the oxidant (C) is one or more members selected from the group consisting of metachloroperbenzoic acid, hydrogen peroxide, peracetic acid, perbenzoic acid, tert-butyl hydroperoxide, cumene hydroperoxide, potassium persulfate, and a potassium hydrogen persulfate-potassium hydrogen sulfate-potassium sulfate mixture.

Description

EXAMPLES

(1) The present invention is described in more detail below with reference to Examples; however, the present invention is not limited thereto.

(2) The meanings of the symbols and abbreviations in the Examples are shown below.

(3) Py: pyridine

Example 1 (Synthesis 1 of Ethyl Monofluorobenzoylacetate)

(4) Ethyl benzoylacetate (1.0 mmol), p-iodobenzoic acid (0.2 eq.), dichloromethane (4 ml), Py.Math.HF (20 eq. HF), and mCPBA (1.3 eq.) were added, and the mixture was stirred at room temperature for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 18%.

(5) On the other hand, NaOH water was added to the reaction liquid, and the aqueous layer was separated by liquid separation. HCl water was added thereto, and the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 88% of p-iodobenzoic acid.

Example 1-1 (Synthesis 1 of Ethyl Monofluorobenzoylacetate)

(6) It was confirmed that the target product was obtained in a yield of 16% in the same manner as in Example 1, except that p-iodobenzoic acid was changed to the one recovered in Example 1. Further, 84% of p-iodobenzoic acid was recovered.

Example 2 (Synthesis 2 of Ethyl Monofluorobenzoylacetate)

(7) Ethyl benzoylacetate (1.0 mmol), p-iodobenzoic acid (0.2 eq.), dichloromethane (4 ml), Py.Math.HF (40 eq. HF), and mCPBA (1.3 eq.) were added, and the mixture was stirred at room temperature for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 43%.

(8) On the other hand, NaOH water was added to the reaction liquid, and the aqueous layer was separated by liquid separation. HCl water was added thereto, and the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 89% of p-iodobenzoic acid.

Example 2-1 (Synthesis 2 of Ethyl Monofluorobenzoylacetate)

(9) It was confirmed that the target product was obtained in a yield of 40% in the same manner as in Example 2, except that p-iodobenzoic acid was changed to the one recovered in Example 2. Further, 88% of p-iodobenzoic acid was recovered.

Example 3 (Synthesis 3 of Ethyl Monofluorobenzoylacetate)

(10) Ethyl benzoylacetate (1.0 mmol), N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine (0.2 eq.), dichloromethane (4 ml), Py.Math.HF (20 eq. HF), and mCPBA (1.5 eq.) were added, and the mixture was stirred at 40° C. for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 70%.

(11) On the other hand, ethyl acetate and water were added to the reaction liquid, and then the organic layer was separated by liquid separation. HCl water was added thereto, and then the aqueous layer was separated by liquid separation. NaOH water and ethyl acetate were added thereto, and then the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 23% of N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine.

Example 3-1 (Synthesis 3 of Ethyl Monofluorobenzoylacetate)

(12) It was confirmed that the target product was obtained in a yield of 65% in the same manner as in Example 3, except that N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine was changed to the one recovered in Example 3. Further, 20% of N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine was recovered.

Example 4 (Synthesis 4 of Ethyl Monofluorobenzoylacetate)

(13) Ethyl benzoylacetate (1.0 mmol), N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine (0.2 eq.), dichloromethane (4 ml), 55% HF water (28 eq. HF), and mCPBA (1.5 eq.) were added, and the mixture was stirred at 40° C. for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 79%.

(14) On the other hand, ethyl acetate and water were added to the reaction liquid, and then the aqueous layer was separated by liquid separation. NaOH water and ethyl acetate were added thereto, and then the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 20% of N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine.

Example 4-1 (Synthesis 4 of Ethyl Monofluorobenzoylacetate)

(15) It was confirmed that the target product was obtained in a yield of 75% in the same manner as in Example 4, except that N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine was changed to the one recovered in Example 4. Further, 20% of N,N-diethyl-2-(3-iodophenoxy)ethan-1-amine was recovered.

Example 5 (Synthesis 5 of Ethyl Monofluorobenzoylacetate)

(16) Ethyl benzoylacetate (1.0 mmol), 3-(3-iodophenoxy)-N,N-dimethylpropan-1-amine (0.2 eq.), dichloromethane (4 ml), Py.Math.HF (20 eq. HF), and mCPBA (1.5 eq.) were added, and the mixture was stirred at 40° C. for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 60%.

(17) On the other hand, ethyl acetate and water were added to the reaction liquid, and then the organic layer was separated by liquid separation. HCl water was added thereto, and then the aqueous layer was separated by liquid separation. NaOH water and ethyl acetate were added thereto, and then the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 21% of 3-(3-iodophenoxy)-N,N-dimethylpropan-1-amine.

Example 5-1 (Synthesis 5 of Ethyl Monofluorobenzoylacetate)

(18) It was confirmed that the target product was obtained in a yield of 55% in the same manner as in Example 3, except that 3-(3-iodophenoxy)-N,N-dimethylpropan-1-amine was changed to the one recovered in Example 5. Further, 20% of 3-(3-iodophenoxy)-N,N-dimethylpropan-1-amine was recovered.

Example 6 (Synthesis 6 of Ethyl Monofluorobenzoylacetate)

(19) Ethyl benzoylacetate (1.0 mmol), m-iodosylphenylacetic acid (1.3 eq.), dichloromethane (4 ml), and 55% HF water (14 eq. HF) were added, and the mixture was stirred at 45° C. for 17 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 43%.

(20) On the other hand, a sodium hydrogen carbonate aqueous solution and dichloromethane were added to the reaction liquid, and then the aqueous layer was separated by liquid separation. HCl water and dichloromethane were added thereto, and then the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 97% of m-iodophenylacetic acid.

Example 6-1 (Synthesis 6 of Ethyl Monofluorobenzoylacetate)

(21) Ethyl benzoylacetate (1.0 mmol), the m-iodophenylacetic acid (0.2 eq.) recovered in Example 6, dichloromethane (2 ml), Py.Math.HF (20 eq. HF), and mCPBA (1.5 eq.) were added, and the mixture was stirred at 40° C. for 24 hours. The reaction liquid was analyzed by F-NMR, and it was confirmed that the title target product was obtained in a yield of 50%.

(22) On the other hand, a sodium hydrogen carbonate aqueous solution and dichloromethane were added to the reaction liquid, and then the aqueous layer was separated by liquid separation. HCl water and dichloromethane were added thereto, and then the organic layer was separated by liquid separation. Then, the solvent was concentrated, thereby recovering 95% of m-iodophenylacetic acid.