WO2021095577A1 - 含フッ素ピラゾール化合物およびその製造方法 - Google Patents
含フッ素ピラゾール化合物およびその製造方法 Download PDFInfo
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- WO2021095577A1 WO2021095577A1 PCT/JP2020/040923 JP2020040923W WO2021095577A1 WO 2021095577 A1 WO2021095577 A1 WO 2021095577A1 JP 2020040923 W JP2020040923 W JP 2020040923W WO 2021095577 A1 WO2021095577 A1 WO 2021095577A1
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- WIPO (PCT)
- Prior art keywords
- group
- fluorine
- ring
- general formula
- pyrazole compound
- Prior art date
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- -1 pyrazole compound Chemical class 0.000 title claims abstract description 78
- 229910052731 fluorine Inorganic materials 0.000 title claims abstract description 53
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 239000011737 fluorine Substances 0.000 title claims abstract description 51
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 28
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 16
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Chemical group 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- GRLHOORFDPGKMC-UHFFFAOYSA-N 1-fluoro-2-methylprop-1-ene Chemical group CC(C)=CF GRLHOORFDPGKMC-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 239000002516 radical scavenger Substances 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 abstract description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 125000004434 sulfur atom Chemical group 0.000 abstract description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 125000003226 pyrazolyl group Chemical group 0.000 description 15
- 239000000047 product Substances 0.000 description 8
- 125000006413 ring segment Chemical group 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- FSDLLONBRLBIBL-UHFFFAOYSA-N 1,3,3,3-tetrafluoro-1-methoxy-2-(trifluoromethyl)prop-1-ene Chemical compound COC(F)=C(C(F)(F)F)C(F)(F)F FSDLLONBRLBIBL-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- AJPYXWNMWRDHMA-UHFFFAOYSA-N COC1=NN(C(=C1C(F)(F)F)F)C2=CC=CC=N2 Chemical compound COC1=NN(C(=C1C(F)(F)F)F)C2=CC=CC=N2 AJPYXWNMWRDHMA-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 125000002723 alicyclic group Chemical group 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 4
- IIHLPLOLAIBGID-UHFFFAOYSA-N COC1=NN(C(=C1C(F)(F)F)F)C2=C(C=C(C=N2)C(F)(F)F)Cl Chemical compound COC1=NN(C(=C1C(F)(F)F)F)C2=C(C=C(C=N2)C(F)(F)F)Cl IIHLPLOLAIBGID-UHFFFAOYSA-N 0.000 description 4
- QZPFDRDMJCMBLE-UHFFFAOYSA-N COC1=NN(C(=C1C(F)(F)F)F)C2=CN=CC=C2 Chemical compound COC1=NN(C(=C1C(F)(F)F)F)C2=CN=CC=C2 QZPFDRDMJCMBLE-UHFFFAOYSA-N 0.000 description 4
- XOMHZNPLIBYLKO-UHFFFAOYSA-N COC1=NN(C(=C1C(F)(F)F)F)C2=NC3=CC=CC=C3S2 Chemical compound COC1=NN(C(=C1C(F)(F)F)F)C2=NC3=CC=CC=C3S2 XOMHZNPLIBYLKO-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000705989 Tetrax Species 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 229910000039 hydrogen halide Inorganic materials 0.000 description 4
- 239000012433 hydrogen halide Substances 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 description 3
- AQHKYFLVHBIQMS-UHFFFAOYSA-N 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane Chemical compound COC(F)(F)C(C(F)(F)F)C(F)(F)F AQHKYFLVHBIQMS-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 241000209094 Oryza Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000005620 boronic acid group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LWNGJAHMBMVCJR-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenoxy)boronic acid Chemical compound OB(O)OC1=C(F)C(F)=C(F)C(F)=C1F LWNGJAHMBMVCJR-UHFFFAOYSA-N 0.000 description 2
- 0 *OC(F)=C(C(F)(F)F)C(F)(F)F Chemical compound *OC(F)=C(C(F)(F)F)C(F)(F)F 0.000 description 2
- KZJUHXVCAHXJLR-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,4-nonafluoro-n-(1,1,2,2,3,3,4,4,4-nonafluorobutylsulfonyl)butane-1-sulfonamide Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F KZJUHXVCAHXJLR-UHFFFAOYSA-N 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- GCSPSGQVZXMPKU-UHFFFAOYSA-N 2-fluorobutanoic acid Chemical compound CCC(F)C(O)=O GCSPSGQVZXMPKU-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- HFKJQIJFRMRSKM-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenoxy]boronic acid Chemical compound OB(O)OC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HFKJQIJFRMRSKM-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- CGAWEMQCFPPWHK-UHFFFAOYSA-N butylimino(tripyrrolidin-1-yl)-$l^{5}-phosphane Chemical group C1CCCN1P(N1CCCC1)(=NCCCC)N1CCCC1 CGAWEMQCFPPWHK-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 150000003983 crown ethers Chemical class 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- JGTNAGYHADQMCM-UHFFFAOYSA-N perfluorobutanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JGTNAGYHADQMCM-UHFFFAOYSA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 2
- RJSAWRPVTKYGIZ-UHFFFAOYSA-N pyridin-3-ylhydrazine;hydrochloride Chemical compound Cl.NNC1=CC=CN=C1 RJSAWRPVTKYGIZ-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- 239000003799 water insoluble solvent Substances 0.000 description 2
- JYSUYJCLUODSLN-UHFFFAOYSA-N 1,3-benzothiazol-2-ylhydrazine Chemical compound C1=CC=C2SC(NN)=NC2=C1 JYSUYJCLUODSLN-UHFFFAOYSA-N 0.000 description 1
- NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical compound C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- XXTPHXNBKRVYJI-UHFFFAOYSA-N 2-pyrazol-1-ylpyridine Chemical group C1=CC=NN1C1=CC=CC=N1 XXTPHXNBKRVYJI-UHFFFAOYSA-N 0.000 description 1
- QDFXRVAOBHEBGJ-UHFFFAOYSA-N 3-(cyclononen-1-yl)-4,5,6,7,8,9-hexahydro-1h-diazonine Chemical compound C1CCCCCCC=C1C1=NNCCCCCC1 QDFXRVAOBHEBGJ-UHFFFAOYSA-N 0.000 description 1
- YJLYGWOUDNVDMM-UHFFFAOYSA-N 3-pyrazol-1-ylpyridine Chemical group C1=CC=NN1C1=CC=CN=C1 YJLYGWOUDNVDMM-UHFFFAOYSA-N 0.000 description 1
- CHMOXOZMBYAKCO-UHFFFAOYSA-N 4-(cyclodecen-1-yl)-2-methyl-5,6,7,8,9,10-hexahydro-1h-triazecine Chemical compound CN1NCCCCCCC(C=2CCCCCCCCC=2)=N1 CHMOXOZMBYAKCO-UHFFFAOYSA-N 0.000 description 1
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- 230000002378 acidificating effect Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
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- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
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- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005070 decynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000005066 dodecenyl group Chemical group C(=CCCCCCCCCCC)* 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- AFFLGGQVNFXPEV-UHFFFAOYSA-N n-decene Natural products CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005071 nonynyl group Chemical group C(#CCCCCCCC)* 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- KVFIZLDWRFTUEM-UHFFFAOYSA-N potassium;bis(trifluoromethylsulfonyl)azanide Chemical compound [K+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F KVFIZLDWRFTUEM-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108091008743 testicular receptors 4 Proteins 0.000 description 1
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000005065 undecenyl group Chemical group C(=CCCCCCCCCC)* 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- the present invention relates to a fluorine-containing pyrazole compound and a method for producing the same.
- fluorine-containing pyrazole compounds have various biological activities.
- compounds having a heterocycle as a substituent at the 1-position of the pyrazole ring and a substituent at the 3- and 5-positions of the pyrazole ring are expected to be used in the fields of pharmaceuticals and agrochemicals.
- Non-Patent Document 1 reports that a compound having a 1- (2-pyridyl) -pyrazole structure has an insecticidal activity of armyworm and diamondback moth.
- Non-Patent Document 2 reports that a compound having a 1- (3-pyridyl) -pyrazole structure has an inhibitory activity on a stress response kinase (Transforming growth factor beta-active kinase 1 (TAK1)).
- TAK1 Transforming growth factor beta-active kinase 1
- the pyrazole ring has a heterocyclic substituent at the 1-position, a substituent at the 3- and 5-positions of the pyrazole ring, and the pyrazole ring.
- I was interested in the development of a compound having a trifluoromethyl group at the 4-position.
- the present inventors have discovered that a heterocyclic structure can be introduced at the 1-position of the pyrazole ring, a trifluoromethyl group at the 4-position, and a specific substituent at the 3- and 5-positions by reacting a specific raw material.
- the present invention comprises a novel fluorine-containing pyrazole compound having a heterocyclic structure at the 1-position, a trifluoromethyl group at the 4-position, and specific substituents at the 3- and 5-positions, which have not been known conventionally. It provides a production method capable of easily producing the fluorine-containing pyrazole compound.
- the gist structure of the present invention is as follows.
- a fluorine-containing pyrazole compound represented by the following general formula (1) represented by the following general formula (1).
- R represents a hydrocarbon group having 1 to 12 carbon atoms
- ring Z is an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. Represents.
- the ring Z contains at least a nitrogen atom as the hetero atom, and the ring Z contains at least a nitrogen atom.
- the fluoroisobutylene derivative represented by the following general formula (2) with the compound represented by the following general formula (3) or a salt thereof, the inclusion represented by the following general formula (1) is included.
- a method for producing a fluorine-containing pyrazole compound which comprises a step of obtaining a fluorine pyrazole compound.
- R represents a hydrocarbon group having 1 to 12 carbon atoms.
- Ring Z represents an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur.
- a method for producing a fluorine-containing pyrazole compound which comprises a step of obtaining a fluorine pyrazole compound.
- R represents a hydrocarbon group having 1 to 12 carbon atoms.
- X represents a halogen atom, -OA 1 , -SO m A 1 (m is an integer of 0 to 3), or -NA 1 A 2 .
- a 1 and A 2 independently represent a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms.
- Ring Z represents an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur.
- the ring Z contains at least a nitrogen atom as the hetero atom and contains at least a nitrogen atom.
- the fluorine-containing pyrazole compound of the present invention is represented by the following general formula (1).
- R represents a hydrocarbon group having 1 to 12 carbon atoms
- ring Z is an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. Represents.
- the fluorine-containing pyrazole compound of the present invention has an aromatic heterocyclic Z group on the 1-position of the pyrazole ring, and specific substituents (-OR, -CF 3 ,) on the 3-position, 4-position, and 5-position of the pyrazole ring. Since it has ⁇ F), it can have an excellent effect from the viewpoint of structural expandability.
- desired biological activity for example, inhibitory activity of hormones and enzymes, bactericidal activity, insecticidal activity, herbicidal activity
- examples of the bactericidal activity include the bactericidal activity of bacteria that have a harmful effect on agricultural products such as the human body and rice.
- the aromatic heterocycle Z located on the 1-position of the pyrazole ring contains at least one atom selected from the group consisting of nitrogen, oxygen, and sulfur as a heteroatom, and the ring Z further has a substituent. You do not have to have it.
- Ring Z imparts desired properties to the fluorine-containing pyrazole compound depending on the number and type of heteroatoms, ring size, number of ring atoms, number of ⁇ electrons constituting ring Z, number, type and presence of substituents, etc. can do. Further, since the substituents on the 3- and 5-positions of the pyrazole ring are different groups (-OR and -F), these groups can be eliminated or reacted to easily derivatize into an asymmetric structure.
- a derivative can be obtained by modifying -OR by reacting a fluorine-containing pyrazole compound under acidic conditions. Further, by reacting the fluorine-containing pyrazole compound under basic conditions, -F can be modified to obtain a derivative.
- the fluorine-containing pyrazole compound of one embodiment is useful in the field of electronic materials such as organic semiconductors and liquid crystals.
- R is not particularly limited as long as it is a hydrocarbon group having 1 to 12 carbon atoms and is composed of a carbon atom and a hydrogen atom, and examples thereof include a chain hydrocarbon group, an aromatic hydrocarbon group, and an alicyclic hydrocarbon group. it can.
- the chain hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 1 to 12, and may be a branched chain hydrocarbon group or a non-branched chain hydrocarbon group.
- the aromatic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 5 to 12, and even if it is an aromatic hydrocarbon group having a substituent, it is an aromatic hydrocarbon group having no substituent. May be good.
- the aromatic hydrocarbon group may have a condensed polycyclic structure.
- the alicyclic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 3 to 12, and even an alicyclic hydrocarbon group having a substituent does not have a substituent. It may be. Further, the alicyclic hydrocarbon group may have a bridging ring structure.
- chain hydrocarbon group examples include methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group, t-butyl group, pentyl group and hexyl group.
- Alkyl groups such as heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group; Alkenyl groups such as ethenyl group, propenyl group, butenyl group, pentenyl group, hexenyl group, heptenyl group, octenyl group, nonenyl group, decenyl group, undecenyl group, dodecenyl group; Examples thereof include an alkynyl group such as an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a hexynyl group, a heptynyl group, an octynyl group, a nonynyl group, a decynyl group, an undecynyl group and a dodecynyl group.
- aromatic hydrocarbon group examples include a phenyl group and a naphthyl group.
- Examples of the alicyclic hydrocarbon group include a saturated or unsaturated cyclic hydrocarbon group, and examples of the cyclic hydrocarbon group include a cyclopropyl group, a cyclobutyl group, a cyclohexyl group, a cyclopentyl group, an adamantyl group, and a norbornyl group.
- the groups can be mentioned.
- R is an alkyl group having 1 to 10 carbon atoms. Since R is an alkyl group having 1 to 10 carbon atoms, the fluoroisobutylene derivative of the general formula (2) and the fluoroisobutane derivative of the general formula (4), which are raw materials for the fluorine-containing pyrazole compound, can be easily prepared. it can.
- Ring Z represents an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur. Ring Z is not particularly limited as long as it is an aromatic heterocycle containing at least one atom of a heteroatom, a nitrogen atom, an oxygen atom, and a sulfur atom, as a ring atom. Ring Z contains one, two, or three heteroatoms. Further, the ring Z may have a monocyclic structure or a condensed ring structure.
- the number of ⁇ electrons constituting the ring Z is 4n + 2 (n is a positive integer), but the number of ⁇ electrons is preferably 6, 10 or 14. It is more preferable that the ring Z contains at least a nitrogen atom as a hetero atom and the number of ⁇ electrons constituting the ring Z is 6 or 10.
- the polarity and flatness of the fluorine-containing pyrazole compound are controlled, so that the dynamics are improved and more effective biological activity can be imparted.
- a fryl group a thienyl group, a pyrrolyl group, a pyridyl group, an oxazolyl group, an isooxazolyl group, a thiazolyl group, an isothiazolyl group, a benzofuranyl group, a benzothienyl group, an indolyl group and an isoindrill Group
- benzothiazolyl group benzoxazolyl group, pyrazinyl group, pyrimidinyl group, pyridadinyl group, quinolinyl group, isoquinolinyl group, naphthyldinyl group, pyridopyrimidinyl group, pyridopyrazinyl group, triazolyl group, benzotriazolyl group, flopyridyl group, floridyl group.
- Examples thereof include a pyrimidinyl group, a thienopyridyl group, a thienopyridinyl group, a pyrolopyrryl group, a chlorotrifluoromethylpyridyl group and the like.
- the group composed of ring Z is preferably a 2-benzothiazolyl group, a 2-pyridyl group, a 3-pyridyl group, or a 3-chloro-5-trifluoromethyl-2-pyridyl group. Substituents may or may not be further bonded to the ring atom in the group composed of ring Z.
- Examples of the substituent bonded to the ring atom include a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C n F 2n + 1 (where n is an integer of 1-10), a nitro group, a boronic acid group, -OA 1, -SO m a 1 (m is an integer of 0 ⁇ 3), - NA 1 a 2, -COOA 1 or -CONA 1 a 2 (a 1, a 2 are each independently a hydrogen atom or a C (Representing a hydrocarbon group of numbers 1 to 10) can be mentioned.
- the method for producing the fluorine-containing pyrazole compound of one embodiment is (A) By reacting the fluoroisobutylene derivative represented by the following general formula (2) with the compound represented by the following general formula (3) or a salt thereof, the inclusion represented by the following general formula (1) is included. It has a step of obtaining a fluoropyrazole compound.
- R represents a hydrocarbon group having 1 to 12 carbon atoms.
- Ring Z represents an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur.
- the step of obtaining the fluorine-containing pyrazole compound (a) is preferably carried out in the presence of a fluoride ion scavenger. It is preferable to react the fluoroisobutylene derivative represented by the general formula (2) with the compound represented by the general formula (3) or a salt thereof in the presence of a fluoride ion scavenger.
- the fluoride ion trapping agent is not particularly limited as long as it is a substance having a function of trapping fluoride ions, and the fluoride ion trapping agent includes lithium, sodium, magnesium, potassium, calcium, tetramethylammonium, trifluoroacetic acid, and hepta.
- Fluorobutyric acid methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid, nonafluorobutanesulfonic acid, bis (trifluoromethanesulfonyl) imide, bis (nonafluorobutanesulfonyl) imide, N, N -Hexafluoropropane-1,3-disulfonylimide, tetraphenylboric acid, tetrax [3,5-bis (trifluoromethyl) phenyl] boric acid, tetrax (pentafluorophenyl) borate can be mentioned.
- the cation derived from the fluoride ion scavenger captures the fluorine ion liberated from the fluoroisobutylene derivative represented by the general formula (2) during the reaction and precipitates it as a salt having low solubility in an organic solvent. It is considered that the fluorine-containing pyrazole compound represented by the above general formula (1) can be obtained in a high yield.
- the ring Z may have a monocyclic structure or a condensed ring structure.
- the number of ⁇ electrons constituting the ring Z is preferably 6, 10 or 14, and the ring Z contains at least a nitrogen atom as a hetero atom, and the number of ⁇ electrons constituting the ring Z is 6 or 10. More preferably.
- R in the general formulas (1) and (2) preferably represents an alkyl group having 1 to 10 carbon atoms. Substituents may or may not be further bonded to the ring atom in the group composed of ring Z.
- Examples of the substituent bonded to the ring atom include a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C n F 2n + 1 (where n is an integer of 1-10), a nitro group, a boronic acid group, -OA 1, -SO m a 1 (m is an integer of 0 ⁇ 3), - NA 1 a 2, -COOA 1 or -CONA 1 a 2 (a 1, a 2 are each independently a hydrogen atom or a C (Representing a hydrocarbon group of numbers 1 to 10) can be mentioned.
- reaction of the above (a) between the fluoroisobutylene derivative represented by the general formula (2) and the compound represented by the general formula (3) is represented by the following reaction formula (A).
- the counterion is not particularly limited as long as it is a monovalent anion, and examples thereof include halide ions such as F ⁇ , Cl ⁇ , Br ⁇ , and I ⁇ .
- the reaction (a) above can be carried out in one step in the presence of a hydrogen halide scavenger. Therefore, the fluorine-containing pyrazole compound of the above general formula (1) can be easily obtained.
- a cyclic pyrazole structure is formed between the fluoroisobutylene derivative and the amidino group of the compound of the general formula (3).
- a group derived from the ring structure Z of the compound of the general formula (3) is located at the 1-position of the pyrazole structure.
- -OR, CF 3 , and F derived from the fluoroisobutylene derivative are located at the 3-position, 4-position, and 5-position of the pyrazole structure, respectively.
- the hydrogen halide trapping agent is formed from a hydrogen atom derived from an amidino group in the compound of the general formula (3) in the reaction formula of the above (A) and a fluorine atom derived from a fluoroisobutylene derivative of the general formula (2). It is a substance having a function of capturing hydrogen fluoride (HF).
- Hydrogen halide trapping agents include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium fluoride, potassium fluoride, pyridine, triethylamine, diisopropylethylamine, diazabicyclononen, and diazabicycloun.
- Organic nitrogen derivatives such as decene, methyltriazabicyclodecene, diazabicyclooctane, and phosphazene base can be used.
- the reaction temperature during the reaction of (a) above is preferably 0 to 100 ° C., more preferably 5 to 50 ° C., and even more preferably 10 to 20 ° C.
- the reaction time during the reaction of (a) above is preferably 1 to 48 hours, more preferably 2 to 36 hours, still more preferably 4 to 24 hours.
- Solvents used in the reaction (a) above include aprotices such as tetrahydrofuran, monoglime, jigglime, triglime, tetraglyme, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethyleneurea, tetramethylurea, dimethylsulfoxide, and sulfolane. Examples thereof include a sex polar solvent or a two-phase solvent in which a protonic polar solvent such as water and a water-insoluble solvent such as dichloromethane, toluene and diethyl ether are used.
- quaternary ammonium halides such as benzyltriethylammonium chloride, quaternary phosphonium halides, crown ethers and the like can be used.
- the method for producing the fluorine-containing pyrazole compound of another embodiment is (B) By reacting the fluoroisobutane derivative represented by the following general formula (4) with the compound represented by the following general formula (3) or a salt thereof, the inclusion represented by the following general formula (1) is included. It has a step of obtaining a fluoropyrazole compound.
- R represents a hydrocarbon group having 1 to 12 carbon atoms.
- X represents a halogen atom, -OA 1 , -SO m A 1 (m is an integer of 0 to 3), or -NA 1 A 2 .
- a 1 and A 2 independently represent a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms.
- Ring Z represents an aromatic heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur.
- the step of obtaining the fluorine-containing pyrazole compound of (b) above is preferably carried out in the presence of a fluoride ion scavenger. It is preferable to react the fluoroisobutane derivative represented by the general formula (4) with the compound represented by the general formula (3) or a salt thereof in the presence of a fluoride ion scavenger.
- the fluoride ion trapping agent is not particularly limited as long as it is a substance having a function of trapping fluoride ions, and the fluoride ion trapping agent includes lithium, sodium, magnesium, potassium, calcium, tetramethylammonium, trifluoroacetic acid, and hepta.
- Fluorobutyric acid methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, trifluoromethanesulfonic acid, nonafluorobutanesulfonic acid, bis (trifluoromethanesulfonyl) imide, bis (nonafluorobutanesulfonyl) imide, N, N -Hexafluoropropane-1,3-disulfonylimide, tetraphenylboric acid, tetrax [3,5-bis (trifluoromethyl) phenyl] boric acid, tetrax (pentafluorophenyl) borate can be mentioned.
- the cation derived from the fluoride ion scavenger captures the fluorine ion liberated from the fluoroisobutane derivative represented by the general formula (4) during the reaction and precipitates it as a salt having low solubility in an organic solvent. It is considered that the fluorine-containing pyrazole compound represented by the above general formula (1) can be obtained in a high yield.
- the ring Z may have a monocyclic structure or a condensed ring structure.
- the number of ⁇ electrons constituting the ring Z is preferably 6, 10 or 14, and the ring Z contains at least a nitrogen atom as a hetero atom, and the number of ⁇ electrons constituting the ring Z is 6 or 10. More preferably.
- R in the general formulas (1) and (4) preferably represents an alkyl group having 1 to 10 carbon atoms. Substituents may or may not be further bonded to the ring atom in the group composed of ring Z.
- Examples of the substituent bonded to the ring atom include a halogen atom, a hydrocarbon group having 1 to 10 carbon atoms, -C n F 2n + 1 (where n is an integer of 1-10), a nitro group, a boronic acid group, -OA 1, -SO m a 1 (m is an integer of 0 ⁇ 3), - NA 1 a 2, -COOA 1 or -CONA 1 a 2 (a 1, a 2 are each independently a hydrogen atom or a C (Representing a hydrocarbon group of numbers 1 to 10) can be mentioned.
- reaction formula (B) The reaction of the above (b) between the fluoroisobutane derivative represented by the general formula (4) and the compound represented by the general formula (3) is represented by the following reaction formula (B).
- each of the compounds of the general formula (3) may be in the form of a salt.
- the counterion is not particularly limited as long as it is a monovalent anion, and examples thereof include halide ions such as F ⁇ , Cl ⁇ , Br ⁇ , and I ⁇ .
- halogen atom that is X examples include F, Cl, Br, and I.
- -OA 1 is X
- a 1 is a hydrogen atom or a C 1-10 contained.
- a 1 and A 2 contained in -NA 1 A 2 which are X independently represent a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms.
- a 1 and A 2 represent a hydrocarbon group having 1 to 10 carbon atoms, for example, it can be a hydrocarbon group having 1 to 10 carbon atoms in the above R.
- the above reaction (B) can be carried out in one step. Therefore, the fluorine-containing pyrazole compound of the above general formula (1) can be easily obtained.
- a cyclic pyrazole structure is formed between the fluoroisobutane derivative (4) and the amidino group of the compound of the general formula (3).
- a group derived from the ring structure Z of the compound of the general formula (3) is located at the 1-position of the pyrazole structure.
- -OR, CF 3 , and F derived from the fluoroisobutane derivative are located at the 3-position, 4-position, and 5-position of the pyrazole structure, respectively.
- the reaction temperature during the reaction of (b) above is preferably 0 to 100 ° C., more preferably 5 to 50 ° C., and even more preferably 10 to 20 ° C.
- the reaction time during the reaction of (b) above is preferably 1 to 48 hours, more preferably 2 to 36 hours, still more preferably 4 to 24 hours.
- the same hydrogen halide scavenger as in (a) above can be used.
- the solvent used in the reaction (b) is aprotic such as tetrahydrofuran, monoglime, jiglime, triglime, tetraglime, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethyleneurea, tetramethylurea, dimethylsulfoxide, and sulfolane.
- aprotic such as tetrahydrofuran, monoglime, jiglime, triglime, tetraglime, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethyleneurea, tetramethylurea, dimethylsulfoxide, and sulfolane.
- quaternary ammonium halides such as benzyltriethylammonium chloride, quaternary phosphonium halides, crown ethers and the like can be used.
- Example 2 Production of 5-Fluoro-3-methoxy-1- (2-pyridyl) -4-trifluoromethylpyrazole Under ice-water cooling, in 100 g of THF (tetrahydrofuran), 5 g (46 mmol) of 2-hydrazinopyridine, 1,3,3 , 3-Tetrafluoro-1-methoxy-2-trifluoromethyl-1-propen 13 g (60 mmol) was added to obtain THF solution 1. Subsequently, 40 g of diazabicycloundecene 27 g (180 mmol) in THF solution 2 was added dropwise to the THF solution 1 so that the internal temperature did not exceed 10 ° C.
- THF tetrahydrofuran
- Example 3 Production of 5-Fluoro-3-methoxy-1- (3-pyridyl) -4-trifluoromethylpyrazole Under ice-water cooling, in 100 g of THF (tetrahydrofuran), 5 g (34 mmol) of 3-hydrazinopyridine hydrochloride, 1,3 , 3,3-Tetrafluoro-1-methoxy-2-trifluoromethyl-1-propen (9.5 g) (45 mmol) was added to obtain THF solution 1. Subsequently, 40 g of diazabicycloundecene 27 g (180 mmol) in THF solution 2 was added dropwise to the THF solution 1 so that the internal temperature did not exceed 10 ° C.
- THF tetrahydrofuran
- Example 4 Instead of 1,3,3,3-tetrafluoro-1-methoxy-2- (trifluoromethyl) -1-propen of Example 1, 1,1,1,3,3-pentafluoro-3-methoxy Production of 5-fluoro-3-methoxy-1- (2-benzothiazolyl) -4-trifluoromethylpyrazole using -2- (trifluoromethyl) -propane
- THF tetrahydrofuran
- 2 -Hydradinobenzthiazole 5 g bis (trifluoromethanesulfonyl) imide potassium 39 g (120 mmol)
- THF solution 2 of 49 g (160 mmol) of tertiary butyliminotripyrrolidinophosphorane was added dropwise to the above THF solution 1 so that the internal temperature did not exceed 10 ° C.
- the mixed solution of THF solutions 1 and 2 was kept warm to room temperature for about 72 hours.
- the analysis result of the obtained compound was similar to the product of Example 1.
- Example 5 Instead of 1,3,3,3-tetrafluoro-1-methoxy-2- (trifluoromethyl) -1-propen of Example 2, 1,1,1,3,3-pentafluoro-3-methoxy Production of 5-fluoro-3-methoxy-1- (2-pyridyl) -4-trifluoromethylpyrazole using -2- (trifluoromethyl) -propane under ice-water cooling, in 100 g of THF (tetrahydrofuran), 2 -Hydrazinopyridine 5 g (46 mmol) and 1,1,1,3,3-pentafluoro-3-methoxy-2- (trifluoromethyl) -propane 14 g (60 mmol) were added to obtain THF solution 1.
- THF tetrahydrofuran
- Example 6 Instead of 1,3,3,3-tetrafluoro-1-methoxy-2- (trifluoromethyl) -1-propen of Example 3, 1,1,1,3,3-pentafluoro-3-methoxy Production of 5-fluoro-3-methoxy-1- (3-pyridyl) -4-trifluoromethylpyrazole using -2- (trifluoromethyl) -propane in 100 g of THF (tetrahydrofuran) under ice-water cooling, 3 -Hydrazinopyridine hydrochloride 5 g (34 mmol) and 1,1,1,3,3-pentafluoro-3-methoxy-2- (trifluoromethyl) -propane 10 g (45 mmol) were added to obtain THF solution 1.
- THF tetrahydrofuran
- Example 7 Production of 1- (3-chloro-5-trifluoromethyl-2-pyridyl) -5-fluoro-3-methoxy-4-trifluoromethylpyrazole 3-chloro-2-hydrazinyl-5- (trifluoro) in 15 ml of tetrahydrofuran 2.3 g (7.2 mmol) of potassium bis (trifluoromethanesulfonyl) imide in a solution in which 0.5 g (2.4 mmol) of methyl) pyridine is dissolved, 1,3,3,3-tetrafluoro-1-methoxy.
Abstract
Description
[1]下記一般式(1)で表される、含フッ素ピラゾール化合物。
[2]前記環Zを構成するπ電子数が6個、10個または14個である、上記[1]に記載の含フッ素ピラゾール化合物。
[3]前記環Zは、前記ヘテロ原子として少なくとも窒素原子を含み、
前記環Zを構成するπ電子数が6個または10個である、上記[1]または[2]に記載の含フッ素ピラゾール化合物。
[4]下記一般式(2)で表されるフルオロイソブチレン誘導体と、下記一般式(3)で表される化合物またはその塩とを反応させることにより、下記一般式(1)で表される含フッ素ピラゾール化合物を得る工程を有する、含フッ素ピラゾール化合物の製造方法。
Rは炭素数1~12の炭化水素基を表し、
環Zは窒素、酸素、および硫黄からなる群から選択される少なくとも一種のヘテロ原子を含む芳香族複素環を表す。)
[5]下記一般式(4)で表されるフルオロイソブタン誘導体と、下記一般式(3)で表される化合物またはその塩とを反応させることにより、下記一般式(1)で表される含フッ素ピラゾール化合物を得る工程を有する、含フッ素ピラゾール化合物の製造方法。
Rは炭素数1~12の炭化水素基を表し、
Xはハロゲン原子、-OA1、-SOmA1(mは0~3の整数である)、または-NA1A2を表し、
A1、A2はそれぞれ独立して、水素原子または炭素数1~10の炭化水素基を表し、
環Zは窒素、酸素、および硫黄からなる群から選択される少なくとも一種のヘテロ原子を含む芳香族複素環を表す。)
[6]前記含フッ素ピラゾール化合物を得る工程は、フッ化物イオン捕捉剤の存在下で行われる、上記[4]または[5]に記載の含フッ素ピラゾール化合物の製造方法。
[7]前記環Zを構成するπ電子数が6個、10個または14個である、上記[4]から[6]までの何れか1つに記載の含フッ素ピラゾール化合物の製造方法。
[8]前記環Zは、前記ヘテロ原子として少なくとも窒素原子を含み、
前記環Zを構成するπ電子数が6個または10個である、上記[4]から[7]までの何れか1つに記載の含フッ素ピラゾール化合物の製造方法。
本発明の含フッ素ピラゾール化合物は下記一般式(1)で表される。
エテニル基、プロペニル基、ブテニル基、ペンテニル基、ヘキセニル基、ヘプテニル基、オクテニル基、ノネニル基、デセニル基、ウンデセニル基、ドデセニル基等のアルケニル基;
エチニル基、プロピニル基、ブチニル基、ペンチニル基、ヘキシニル基、ヘプチニル基、オクチニル基、ノニニル基、デシニル基、ウンデシニル基、ドデシニル基等のアルキニル基等を挙げることができる。
これらの基の中でも、環Zから構成される基は、2-ベンゾチアゾリル基、2-ピリジル基、3-ピリジル基、3-クロロ-5-トリフルオロメチル-2-ピリジル基であることが好ましい。環Zから構成される基中の環原子にはさらに置換基が結合していても、置換基が結合していなくてもよい。環原子に結合する置換基としては例えば、ハロゲン原子、炭素数1~10の炭化水素基、-CnF2n+1(nは1~10の整数である)、ニトロ基、ボロン酸基、-OA1、-SOmA1(mは0~3の整数である)、-NA1A2、-COOA1または-CONA1A2(A1、A2はそれぞれ独立して、水素原子または炭素数1~10の炭化水素基を表す)を挙げることができる。
一実施形態の含フッ素ピラゾール化合物の製造方法は、
(a)下記一般式(2)で表されるフルオロイソブチレン誘導体と、下記一般式(3)で表される化合物またはその塩とを反応させることにより、下記一般式(1)で表される含フッ素ピラゾール化合物を得る工程
を有する。
Rは炭素数1~12の炭化水素基を表し、
環Zは窒素、酸素、および硫黄からなる群から選択される少なくとも一種のヘテロ原子を含む芳香族複素環を表す。)
好ましくは、上記(a)の含フッ素ピラゾール化合物を得る工程は、フッ化物イオン捕捉剤の存在下で行われるのが好ましい。上記一般式(2)で表されるフルオロイソブチレン誘導体と、上記一般式(3)で表される化合物またはその塩とを、フッ化物イオン捕捉剤の存在下で反応させるのが好ましい。フッ化物イオン捕捉剤はフッ素イオンを捕捉する機能を有する物質であれば特に限定されず、フッ化物イオン捕捉剤としては、リチウム、ナトリウム、マグネシウム、カリウム、カルシウム、テトラメチルアンモニウム、トリフルオロ酢酸、ヘプタフルオロ酪酸、メタンスルホン酸、エタンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸、トリフルオロメタンスルホン酸、ノナフルオロブタンスルホン酸、ビス(トリフルオロメタンスルホニル)イミド、ビス(ノナフルオロブタンスルホニル)イミド、N,N-ヘキサフルオロプロパン-1,3-ジスルホニルイミド、テトラフェニルホウ酸、テトラキス[3,5-ビス(トリフルオロメチル)フェニル]ホウ酸、テトラキス(ペンタフルオロフェニル)ホウ酸塩を挙げることができる。フッ化物イオン捕捉剤に由来するカチオンは、反応中に一般式(2)で表されるフルオロイソブチレン誘導体から遊離したフッ素イオンを捕捉し、有機溶媒への溶解性の低い塩として析出させることで反応が促進され、高い収率で、上記一般式(1)で表される含フッ素ピラゾール化合物を得ることができるものと考えられる。
(b)下記一般式(4)で表されるフルオロイソブタン誘導体と、下記一般式(3)で表される化合物またはその塩とを反応させることにより、下記一般式(1)で表される含フッ素ピラゾール化合物を得る工程
を有する。
Rは炭素数1~12の炭化水素基を表し、
Xはハロゲン原子、-OA1、-SOmA1(mは0~3の整数である)、または-NA1A2を表し、
A1、A2はそれぞれ独立して、水素原子または炭素数1~10の炭化水素基を表し、
環Zは窒素、酸素、および硫黄からなる群から選択される少なくとも一種のヘテロ原子を含む芳香族複素環を表す。)
好ましくは、上記(b)の含フッ素ピラゾール化合物を得る工程は、フッ化物イオン捕捉剤の存在下で行われるのが好ましい。上記一般式(4)で表されるフルオロイソブタン誘導体と、上記一般式(3)で表される化合物またはその塩とを、フッ化物イオン捕捉剤の存在下で反応させるのが好ましい。フッ化物イオン捕捉剤はフッ素イオンを捕捉する機能を有する物質であれば特に限定されず、フッ化物イオン捕捉剤としては、リチウム、ナトリウム、マグネシウム、カリウム、カルシウム、テトラメチルアンモニウム、トリフルオロ酢酸、ヘプタフルオロ酪酸、メタンスルホン酸、エタンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸、トリフルオロメタンスルホン酸、ノナフルオロブタンスルホン酸、ビス(トリフルオロメタンスルホニル)イミド、ビス(ノナフルオロブタンスルホニル)イミド、N,N-ヘキサフルオロプロパン-1,3-ジスルホニルイミド、テトラフェニルホウ酸、テトラキス[3,5-ビス(トリフルオロメチル)フェニル]ホウ酸、テトラキス(ペンタフルオロフェニル)ホウ酸塩を挙げることができる。フッ化物イオン捕捉剤に由来するカチオンは、反応中に一般式(4)で表されるフルオロイソブタン誘導体から遊離したフッ素イオンを捕捉し、有機溶媒への溶解性の低い塩として析出させることで反応が促進され、高い収率で、上記一般式(1)で表される含フッ素ピラゾール化合物を得ることができるものと考えられる。
5-フルオロ-3-メトキシ-1-(2-ベンゾチアゾリル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、2-ヒドラジノベンズチアゾール5g(30mmol)、ビス(トリフルオロメタンスルホニル)イミドカリウム29g(91mmol)、および1,3,3,3-テトラフルオロ-1-メトキシ-2-トリフルオロメチル-1-プロペン8.3g(39mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ターシャリーブチルイミノトリピロリジノホスホラン37g(120mmol)のTHF溶液2を60g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持することで5-フルオロ-3-メトキシ-1-(2-ベンゾチアゾリル)-4-トリフルオロメチルピラゾールを製造した。その後、ヘキサン-酢酸エチル=7:3(体積比)の混合溶媒を用いたシリカゲルのカラム精製により、下記式(C)で表される5-フルオロ-3-メトキシ-1-(2-ベンゾチアゾリル)-4-トリフルオロメチルピラゾール(分子量317.26)を950mg、単離した。5-フルオロ-3-メトキシ-1-(2-ベンゾチアゾリル)-4-トリフルオロメチルピラゾールの単離収率は10%であった。
マススペクトル(APCl、m/z):317([M]+)
1H-NMR(300MHz、CDCl3) δppm:7.97(d,1H)、7.84(d,1H)、7.51(dt,1H)、7.40(dt,1H)、4.07(s,3H)
19F-NMR(300MHz、C6F6) δppm:-58.9(d,3F)、-114.2(dd,1F)
5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、2-ヒドラジノピリジン5g(46mmol)、1,3,3,3-テトラフルオロ-1-メトキシ-2-トリフルオロメチル-1-プロペン13g(60mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ジアザビシクロウンデセン27g(180mmol)のTHF溶液2を40g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持することで5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールを製造した。その後、ヘキサン-酢酸エチル=7:3(体積比)の混合溶媒を用いたシリカゲルのカラム精製により、下記式(D)で表される5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾール(分子量261.18)を360mg、単離した。5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールの単離収率は3%であった。
マススペクトル(APCl、m/z):261([M]+)
1H-NMR(300MHz、CDCl3) δppm:8.32(d,1H)、7.67(dt,1H)、7.50(d,1H)、7.09(m,1H)、3.86(s,3H)
19F-NMR(300MHz、C6F6) δppm:-58.1(d,3F)、-115.7(dd,1F)
5-フルオロ-3-メトキシ-1-(3-ピリジル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、3-ヒドラジノピリジン塩酸塩5g(34mmol)、1,3,3,3-テトラフルオロ-1-メトキシ-2-トリフルオロメチル-1-プロペン9.5g(45mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ジアザビシクロウンデセン27g(180mmol)のTHF溶液2を40g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持することで5-フルオロ-3-メトキシ-1-(3-ピリジル)-4-トリフルオロメチルピラゾールを製造した。その後、ヘキサン-酢酸エチル=7:3(体積比)の混合溶媒を用いたシリカゲルのカラム精製により、下記式(E)で表される5-フルオロ-3-メトキシ-1-(3-ピリジル)-4-トリフルオロメチルピラゾール(分子量261.18)を621mg、単離した。5-フルオロ-3-メトキシ-1-(3-ピリジル)-4-トリフルオロメチルピラゾールの単離収率は7%であった。
マススペクトル(APCl、m/z):261([M]+)
1H-NMR(300MHz、CDCl3) δppm:8.92(s,1H)、8.61(d,1H)、7.93(m,1H)、7.44(m,1H)、4.02(s,3H)
19F-NMR(300MHz、C6F6) δppm:-58.5(d,3F)、-119.7(dd,1F)
実施例1の1,3,3,3-テトラフルオロ-1-メトキシ-2-(トリフルオロメチル)-1-プロペンの代わりに、1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパンを使用した、5-フルオロ-3-メトキシ-1-(2-ベンゾチアゾリル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、2-ヒドラジノベンズチアゾール5g(30mmol)、ビス(トリフルオロメタンスルホニル)イミドカリウム39g(120mmol)、および1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパン9.1g(39mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ターシャリーブチルイミノトリピロリジノホスホラン49g(160mmol)のTHF溶液2を80g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持した。得られた化合物の分析結果は、実施例1の生成物と同様であった。
実施例2の1,3,3,3-テトラフルオロ-1-メトキシ-2-(トリフルオロメチル)-1-プロペンの代わりに、1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパンを使用した、5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、2-ヒドラジノピリジン5g(46mmol)、1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパン14g(60mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ジアザビシクロウンデセン36g(240mmol)のTHF溶液2を80g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持した。得られた化合物の分析結果は、実施例2の生成物と同様であった。
実施例3の1,3,3,3-テトラフルオロ-1-メトキシ-2-(トリフルオロメチル)-1-プロペンの代わりに、1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパンを使用した、5-フルオロ-3-メトキシ-1-(3-ピリジル)-4-トリフルオロメチルピラゾールの製造
氷水冷下、THF(テトラヒドロフラン)100gに、3-ヒドラジノピリジン塩酸塩5g(34mmol)、1,1,1,3,3-ペンタフルオロ-3-メトキシ-2-(トリフルオロメチル)-プロパン10g(45mmol)を加えてTHF溶液1を得た。続いて、上記THF溶液1中に、内温が10℃を越えないようにして、ジアザビシクロウンデセン34g(220mmol)のTHF溶液2を60g、滴下した。THF溶液1と2の混合溶液を室温まで昇温したまま約72時間、保持した。得られた化合物の分析結果は、実施例3の生成物と同様であった。
1-(3-クロロ-5-トリフルオロメチル-2-ピリジル)-5-フルオロ-3-メトキシ-4-トリフルオロメチルピラゾールの製造
テトラヒドロフラン15mlに3-クロロ-2-ヒドラジニル-5-(トリフルオロメチル)ピリジン0.5g(2.4mmol)を溶解させた溶液中に、カリウムビス(トリフルオロメタンスルホニル)イミド2.3g(7.2mmol)、1,3,3,3-テトラフルオロ-1-メトキシ-2-トリフルオロメチル-1-プロペン0.6g(2.8mmol)と1,8-ジアザビシクロ[5.4.0]-7-ウンデセン1.1g(7.2mmol)を加え室温で17.6時間攪拌して反応液を得た。この後、反応液をカラム精製し、下記式(F)で示される1-(3-クロロ-5-トリフルオロメチル-2-ピリジル)-5-フルオロ-3-メトキシ-4-トリフルオロメチルピラゾール(分子量:363.62)を0.1g(0.2mmol)得た。1-(3-クロロ-5-トリフルオロメチル-2-ピリジル)-5-フルオロ-3-メトキシ-4-トリフルオロメチルピラゾールの単離収率は28.0%であった。
マススペクトル(APCI、m/z):363.6([M]+)
1H-NMR(400MHz,CDCl3) δppm:8.78(dd,J=2.2,1.1Hz,1H),8.20(d,J=1.8Hz,1H),4.01(s,3H)
・イネいもち病に対する評価試験
実施例2で作製した5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールをアセトンに溶かし、100,000ppmの5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールを含有するアセトン溶液を調製した。このアセトン溶液1mlに滅菌水を加えて50mlとし、2000ppm被験液を調製した。2000ppm被験液を、別途作製したオートミール培地に1000μl滴下処理した後、風乾させた。続いて、8mmのイネいもち病ディスクを、菌叢がオートミール培地の処理面に接するように設置した。その後、オートミール培地を25℃の恒温室に7日間静置した後、菌糸の伸長長さを調査した。下記式に従って算出した防除価は80であり、実施例2で作製した5-フルオロ-3-メトキシ-1-(2-ピリジル)-4-トリフルオロメチルピラゾールは優れた殺菌活性を有することを確認できた。
防除価={(無処理の菌糸伸長長さ平均-処理済の菌糸伸長長さ平均)/無処理の菌糸伸長長さ平均 }×100。
なお、上記式において「無処理」とは、被験液として滅菌水のみを培地に滴下処理したことを表す。
「処理済」とは、設定濃度に希釈調整処理を行った被験液を培地に滴下処理したことを表す。
Claims (8)
- 前記環Zを構成するπ電子数が6個、10個または14個である、請求項1に記載の含フッ素ピラゾール化合物。
- 前記環Zは、前記ヘテロ原子として少なくとも窒素原子を含み、
前記環Zを構成するπ電子数が6個または10個である、請求項1または2に記載の含フッ素ピラゾール化合物。 - 下記一般式(4)で表されるフルオロイソブタン誘導体と、下記一般式(3)で表される化合物またはその塩とを反応させることにより、下記一般式(1)で表される含フッ素ピラゾール化合物を得る工程を有する、含フッ素ピラゾール化合物の製造方法。
Rは炭素数1~12の炭化水素基を表し、
Xはハロゲン原子、-OA1、-SOmA1(mは0~3の整数である)、または-NA1A2を表し、
A1、A2はそれぞれ独立して、水素原子または炭素数1~10の炭化水素基を表し、
環Zは窒素、酸素、および硫黄からなる群から選択される少なくとも一種のヘテロ原子を含む芳香族複素環を表す。) - 前記含フッ素ピラゾール化合物を得る工程は、フッ化物イオン捕捉剤の存在下で行われる、請求項4または5に記載の含フッ素ピラゾール化合物の製造方法。
- 前記環Zを構成するπ電子数が6個、10個または14個である、請求項4から6までの何れか1項に記載の含フッ素ピラゾール化合物の製造方法。
- 前記環Zは、前記ヘテロ原子として少なくとも窒素原子を含み、
前記環Zを構成するπ電子数が6個または10個である、請求項4から7までの何れか1項に記載の含フッ素ピラゾール化合物の製造方法。
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