Ring-contraction compounds of perfluoro cyclic sulfonylimide compounds substituted with benzene-based aromatic hydrocarbon groups, and method for producing the same

Abstract

To provide a method for producing compounds having a perfluoro five-membered ring sulfonylamide and compounds having perfluoro azacyclobutane (azetidine).SOLUTION: There is provided a method for producing compounds represented by formulas (2) and (3) by subjecting a benzene-based aromatic hydrocarbon-substituted perfluoro cyclic sulfonylimide compound represented by formula (1) (where R represents a benzene-based aromatic hydrocarbon group) to the action of a photosensitizer under light irradiation.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a compound obtained by ring contraction of a perfluorocyclic sulfonylimide compound substituted with a benzene-based aromatic hydrocarbon group, and a method for producing the same. [Background technology]

[0002] Organofluorine compounds are known to have several advantages due to the characteristic size and electronic properties of the fluorine atom, including the mimic effect of three-dimensional molecular recognition in living organisms (due to the similarity of the atomic radii of fluorine and hydrogen), the blocking effect (protection of metabolic sites and avoidance of associated toxicity due to the stronger C—F bond compared to C—H bond), and the lipophilic effect (facilitation of absorption and transport in the body due to improved lipid solubility). Chemical modifications that take advantage of these effects have led to the development of numerous pharmaceuticals and agricultural chemicals. Furthermore, methods for introducing fluoroalkyl groups, which mimic alkyl group substituents, are currently being developed.

[0003] Meanwhile, compounds having sulfonylamides, including compounds having cyclic sulfonylamides, are widely used as herbicides and fungicides. Patent Document 1 discloses a method for producing vinyltrifluoromethanesulfonylamides having fluoroalkyl groups. In addition, azacyclobutane (azetidine) is a useful molecular skeleton that can serve as the basis for the development of pharmaceuticals and agricultural chemicals.

[0004] Based on the above effects and past achievements, research and development of pharmaceutical and agricultural raw materials containing perfluorocyclic sulfonylamides is underway. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 63-150258 [Non-patent literature]

[0006] [Non-Patent Document 1] Bishop, BC; Hynes, JB ;Bigelow, LAJ Am. Chem. Soc. 1962, 84, 3409-3410 Summary of the Invention [Problem to be solved by the invention]

[0007] Although Patent Document 1 discloses a method for producing vinyltrifluoromethanesulfonylamide having a perfluoroalkyl group introduced therein, it is unclear whether this method can be applied to the production of compounds having cyclic sulfonylamides. Furthermore, no method for producing compounds having five-membered cyclic sulfonylamides in which all C-H bonds are fluorinated has been reported to date, including Patent Document 1. Furthermore, although Non-Patent Document 1 describes a method for producing perfluoroazacyclopentane, it is unclear whether this method can be applied to the production of compounds having perfluoroazacyclobutane (azetidine). Therefore, although research and development of pharmaceutical raw materials and agricultural chemical raw materials having perfluorocyclic sulfonylamides is progressing, it has been difficult to design precise molecular structures for these raw material compounds. In view of the above circumstances, an object of the present invention is to provide a compound having a perfluoro five-membered ring sulfonyl amide and a compound having a perfluoroazacyclobutane (azetidine), as well as methods for producing the same. [Means for solving the problem]

[0008] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that by treating a naphthyl-substituted perfluorocyclic sulfonylimide compound with a photosensitizer under light irradiation, some or all of the sulfur dioxide is eliminated, and a ring contraction reaction proceeds, thereby completing the present invention.

[0009] That is, the present invention relates to the following: [1] A method for producing compounds represented by formula (2) and formula (3) by reacting a photosensitizer with a benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide compound represented by formula (1) (wherein R represents a benzene-based aromatic hydrocarbon group) under light irradiation. [ka] [2] The method according to the above [1], wherein the benzene-based aromatic hydrocarbon group is a naphthyl group. [3] The method according to the above [1], wherein the benzene-based aromatic hydrocarbon group is substituted with an optionally substituted aromatic hydrocarbon group or an optionally substituted heterocyclic group. [4] The method according to the above [3], wherein the aromatic hydrocarbon group which may have a substituent is an aromatic hydrocarbon group substituted with a halogen. [5] The method according to [4] above, wherein the halogen is fluorine. [6] A compound represented by formula (2) (wherein R represents a benzene-based aromatic hydrocarbon group). [ka] [7] A compound represented by formula (3) (wherein R represents a benzene-based aromatic hydrocarbon group). [ka] [Effects of the Invention]

[0010] According to the production method of the present invention, a compound having a contracted ring can be obtained by eliminating part or all of the sulfur dioxide from a perfluoroalkyl cyclic sulfonylimide compound having a predetermined substituent under mild conditions in a simple manner and in a short time. DETAILED DESCRIPTION OF THE INVENTION

[0011] The method for producing the compounds represented by formula (2) and formula (3) of the present invention is a method for reacting a photosensitizer with a benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide compound represented by formula (1) (wherein R represents a benzene-based aromatic hydrocarbon group) under light irradiation. [ka]

[0012] In the compound represented by formula (1) used in the production method of the present invention, R in the formula represents a benzene-based aromatic hydrocarbon group. The benzene-based aromatic hydrocarbon group is not particularly limited, but includes a phenyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-azulenyl group, a 3-indenyl group, a 1-azulenyl group, an anthracenyl group, a phenanthrenyl group, and the like.

[0013] The "benzene-based aromatic hydrocarbon group" may have a substituent, and examples of the substituent include an aromatic hydrocarbon group that may have a substituent and a heterocyclic group that may have a substituent. Examples of the aromatic hydrocarbon group that may have a substituent include an optionally substituted phenyl group and an optionally substituted 1-naphthyl group. Further, examples of the substituent include a linear or branched lower alkyl group, a halogen atom, and an aromatic hydrocarbon group. Examples of the heterocyclic group that may have a substituent include a 5- to 10-membered heterocyclic group containing at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom. Further, examples of the substituent include a linear or branched lower alkyl group, a halogen atom, and an aromatic hydrocarbon group. Whether the substituent of the benzene-based aromatic hydrocarbon group is an aromatic hydrocarbon group or a heterocyclic group, the substituent on the aromatic hydrocarbon group or the heterocyclic group is preferably a halogen atom, and particularly preferably fluorine.

[0014] Specific examples of the compound represented by formula (1) include compounds represented by the following formulas. [ka]

[0015] The production method of the present invention involves reacting a benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide compound represented by formula (1) with a photosensitizer in an organic solvent under light irradiation.

[0016] The organic solvent in the production method of the present invention is not particularly limited, but examples thereof include organic halogen-based solvents such as chloroform, dichloromethane, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane, and chlorobenzene, as well as acetonitrile, tetrahydrofuran, toluene, benzotrifluoride (trifluorotoluene), hexane, dimethyl sulfoxide, and ethyl acetate. Of these, organic halogen-based solvents, particularly dichloromethane, can be preferably used. The amount of the organic solvent is not particularly limited, but is preferably about 20 times by weight relative to the compound of formula (1).

[0017] The light source for light irradiation in the production method of the present invention is not particularly limited to a particular type, but may be a black light, an LED light having a single wavelength peak such as a blue LED, or an LED light having multiple wavelength peaks such as an LED aquarium light. Preferably, a black light is used. The photosensitizer used in the production method of the present invention is not particularly limited as long as it is a compound that can transition from the ground state to the triplet excited state by absorbing light, and examples thereof include thioxanthone, anthraquinone, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, diacetyl, benzyl, benzophenone, 4-CzIPN, etc. Preferably, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 is used.

[0018] The reaction in the production method of the present invention involves stirring, and the stirring temperature is not particularly limited, but can be carried out at room temperature. Furthermore, as for the reaction (stirring) time, by extending the reaction (stirring) time, the compound represented by formula (2) is converted to the compound represented by formula (3), and thus a larger amount of the compound represented by formula (3) is produced. Therefore, the reaction (stirring) time can be appropriately set within the range of, for example, 2 to 20 hours depending on whether the compound represented by formula (2) or the compound represented by formula (3) is desired.

[0019] The production method of the present invention can synthesize a compound represented by the following formula (2): R in formula (2) is the same benzene-based aromatic hydrocarbon group as R in formula (1). [ka] The compound represented by formula (2) obtained by the production method of the present invention has both a fluorine atom and a sulfonamide structure, and therefore has the effects of both a fluorine atom and a sulfonamide, and can therefore be suitably used in the medical and agrochemical fields as a raw material for pharmaceuticals and agrochemicals.

[0020] The production method of the present invention can synthesize a compound represented by the following formula (3): R in formula (3) is the same benzene-based aromatic hydrocarbon group as R in formula (1). [ka] The compound represented by formula (3) obtained by the production method of the present invention has both a fluorine structure and an azacyclobutane (azetidine) structure, and therefore has the effects of both fluorine and azacyclobutane (azetidine), and can therefore be suitably used in the medical and agricultural chemical fields as a pharmaceutical raw material and an agricultural chemical raw material. [Example]

[0021] The present invention will be described in more detail below using examples, but the present invention is not limited to these examples in any way. [Example 1]

[0022] A 50 mL pear-shaped flask was charged with 4,4,5,5,6,6-hexafluoro-2-(3-(4-fluorophenyl)naphthalen-1-yl)-1,3,2-dithiazinane 1,1,3,3-tetraoxide (128 mg, 0.25 mmol, 1 equiv) as the benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide compound of formula (1) and the photosensitizer thioxanthone (5 mg, 0.02 mmol, 0.08 equiv). The atmosphere was then purged with nitrogen. Next, the organic solvent dichloromethane (CHCl: 5 mL) was added. The mixture was irradiated with five 5 mm artillery LEDs with a peak wavelength of 385 nm. The pear-shaped flask was cooled with water and stirred for 18 hours. After stirring was completed, the reaction mixture was transferred to a 50 mL pear-shaped flask and concentrated using an evaporator and a vacuum pump to obtain a crude product (114.1 mg). The resulting mixture was purified by column chromatography to give 3,3,4,4,5,5-hexafluoro-2-(3-(4-fluorophenyl)naphthalen-1-yl)isothiazolidine 1,1-dioxide (65.9 mg, 0.15 mmol, 59%) as the compound of formula (2), and 2,2,3,3,4,4-hexafluoro-1-(3-(4-fluorophenyl)naphthalen-1-yl)azetidine (30.2 mg, 0.078 mmol, 31%) as the compound of formula (3). [ka] (wherein X represents fluorine).

[0023] The synthesis of the compound represented by formula (2) was confirmed as follows. [ka] 3,3,4,4,5,5-hexafluoro-2-(3-(4-fluorophenyl)naphthalen-1-yl)isothiazolidine 1,1-dioxide 1H-NMR (500 MHz, CHLOROFORM-D) δ 8.24 (d, J = 1.6 Hz, 1H), 8.00-7.97 (m, 2H), 7.89 (s, 1H), 7.70-7.65 (m, 4H), 7.24-7.20 (m, 2H); 19F-NMR (470 MHz, CHLOROFORM-D) δ -86.6--87.0 (m, 1F), -97.1--97.5 (m, 1F), -113.7--113.8 (m, 1F), -118.2--118.7 (m, 1F), -119.6--120.1 (m, 1F), -125.9--126.5 (m, 1F), -128.1--128.6 (m, 1F); HRMS (ASAP-TOF) calc. for C 19 H 10 NO2F7S + [M]+ 449.0320, found 449.0319.

[0024] The synthesis of the compound represented by formula (3) was confirmed as follows. [ka] 2,2,3,3,4,4-hexafluoro-1-(3-(4-fluorophenyl)naphthalen-1-yl)azetidine 1H-NMR (500 MHz, CHLOROFORM-D) δ 8.15 (d, J = 1.6 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1H), 7.98-7.96 (m, 1H), 7.75 (d, J = 1.7 Hz, 1H), 7.68-7.61 (m, 4H), 7.23-7.19 (m, 2H); 19F-NMR (470 MHz, CHLOROFORM-D) δ -93.5 (s, 4F), -114.1--114.2 (m, 1F), -128.4 (t, J = 4.3 Hz, 2F); HRMS (ASAP-TOF) calc. for C 19 H 10 NF7 + [M]+ 385.0701, found 385.0699. [Example 2]

[0025] The reaction was carried out in the same manner as in Example 1 except that the stirring time was changed from 18 hours to 2 hours. The reaction conditions other than the stirring time were the same as in Example 1. [Example 3]

[0026] In Example 1, the compound represented by formula (1) was changed to 4,4,5,5,6,6-hexafluoro-2-(3-(4-chlorophenyl)naphthalen-1-yl)-1,3,2-dithiazinane 1,1,3,3-tetraoxide, and the stirring time was changed to 45 hours, and the reaction was carried out. The reaction conditions other than the compound represented by formula (1) and the stirring time were the same as in Example 1.

[0027] The results of Examples 1 to 3 are shown in Table 1 below. [Table 1] [Example 4]

[0028] [ka] A 20- or 30-mL two-necked round-bottom flask was charged with 4,4,5,5,6,6-hexafluoro-2-(3-phenylnaphthalen-1-yl)-1,3,2-dithiazinane 1,1,3,3-tetraoxide (0.1 mmol, 1 equiv) as a benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide compound of formula (1) and a photosensitizer (0.1, 0.05, or 0.01 equiv). The flask was then purged with nitrogen. Dichloromethane (CHCl: 2.5 mL) was then added. The round-bottom flask was cooled with water and irradiated with light, followed by stirring for 2 hours. After stirring, the reaction mixture was transferred to a 50 mL eggplant-shaped flask and concentrated using an evaporator and vacuum pump to obtain the crude product. The yields of the five-membered ring product, 3,3,4,4,5,5-hexafluoro-2-(3-phenylnaphthalen-1-yl)isothiazolidine 1,1-dioxide, and the four-membered ring product, 2,2,3,3,4,4-hexafluoro-1-(3-phenylnaphthalen-1-yl)azetidine, were calculated by F NMR using benzotrifluoride (PhCF3) as an internal standard. The recovery rate (unreacted rate) of SM (starting material) was calculated by 1H NMR. The reaction conditions for the light source, photosensitizer, and number of equivalents of photosensitizer were investigated based on the yield of the five-membered ring product, the yield of the four-membered ring product, and the recovery rate of SM. The results are shown in Table 2 below. [Table 2] The purple LED used was an LED aquarium light with a peak at 398 nm, the black light used was a fluorescent lamp with a peak at 360 nm, and the blue LED used was an LED light with a peak at 455 to 460 nm. [Example 5]

[0029] In Example 4, black light was used as the light source, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 was used as the photosensitizer, and the effect of the organic solvent on the yield of the five-membered ring product, the yield of the four-membered ring product, and the recovery rate of SM was investigated by changing the organic solvent. The results are shown in Table 3 below. [Table 3] In the table, THF represents tetrahydrofuran and DMSO represents dimethyl sulfoxide. [Example 6]

[0030] In Example 4, black light was used as the light source, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 was used as the photosensitizer, and dichloromethane was used as the organic solvent. The stirring time was varied to examine the effect of stirring time on the yield of the five-membered ring product and the four-membered ring product. The results are shown in Table 4 below. [Table 4] [Industrial Applicability]

[0031] According to the production method of the present invention, a compound in which some or all of the sulfur dioxide constituting the compound is eliminated from a perfluoroalkyl cyclic sulfonylimide compound having a predetermined substituent, and a ring-contracted compound can be obtained simply and quickly under mild conditions. Furthermore, according to the production method of the present invention, novel compounds having both fluorine and sulfonamide structures and novel compounds having both fluorine and azacyclobutane (azetidine) structures, which could not be synthesized by conventional production methods, can be synthesized, which can contribute to the development of pharmaceuticals and agricultural chemicals. Therefore, the applicability of the present invention in the pharmaceutical and agricultural chemical fields is extremely high.

Claims

1. A method for producing compounds represented by formula (2) and formula (3) by allowing a photosensitizer to act on a compound having a benzene-based aromatic hydrocarbon group-substituted perfluorocyclic sulfonylimide represented by formula (1) (wherein R represents a benzene-based aromatic hydrocarbon group) under light irradiation. 【Chemical 1】

2. 2. The method according to claim 1, wherein the benzene-based aromatic hydrocarbon group is a naphthyl group.

3. 2. The method according to claim 1, wherein the benzene-based aromatic hydrocarbon group is substituted with an optionally substituted aromatic hydrocarbon group or an optionally substituted heterocyclic group.

4. 4. The method according to claim 3, wherein the aromatic hydrocarbon group which may have a substituent is an aromatic hydrocarbon group substituted with a halogen.

5. 5. The method of claim 4, wherein the halogen is fluorine.

6. A compound represented by formula (2) (wherein R represents a benzene-based aromatic hydrocarbon group): 【Chemistry 2】

7. A compound represented by formula (3) (wherein R represents a benzene-based aromatic hydrocarbon group). 【Chemistry 3】

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