EP1265902A1 - Verfahren zur herstellung von sulfonyl-imidazol-derivaten mittels phasen-transfer-katalyse - Google Patents
Verfahren zur herstellung von sulfonyl-imidazol-derivaten mittels phasen-transfer-katalyseInfo
- Publication number
- EP1265902A1 EP1265902A1 EP01916951A EP01916951A EP1265902A1 EP 1265902 A1 EP1265902 A1 EP 1265902A1 EP 01916951 A EP01916951 A EP 01916951A EP 01916951 A EP01916951 A EP 01916951A EP 1265902 A1 EP1265902 A1 EP 1265902A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- carbon atoms
- optionally substituted
- formula
- atoms
- chlorine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- MCNQDGXBYQRUGL-UHFFFAOYSA-N 2-sulfonylimidazole Chemical class O=S(=O)=C1N=CC=N1 MCNQDGXBYQRUGL-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 238000003408 phase transfer catalysis Methods 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 14
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 claims abstract description 13
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 7
- 239000011230 binding agent Substances 0.000 claims abstract description 7
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 6
- 239000003085 diluting agent Substances 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 173
- -1 cyano, thiocyanato Chemical group 0.000 claims description 137
- 239000000460 chlorine Chemical group 0.000 claims description 53
- 229910052801 chlorine Inorganic materials 0.000 claims description 51
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 48
- 239000011737 fluorine Substances 0.000 claims description 46
- 229910052731 fluorine Inorganic materials 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 26
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 26
- 229910052794 bromium Chemical group 0.000 claims description 26
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 229910052717 sulfur Chemical group 0.000 claims description 25
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 15
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- GZLPFEYTAAXJCP-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-sulfonyl chloride Chemical compound CC1=NOC(C)=C1S(Cl)(=O)=O GZLPFEYTAAXJCP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 7
- RMZRQZISNPQWEM-UHFFFAOYSA-N 2-chloro-6,6-difluoro-[1,3]dioxolo[4,5-f]benzimidazole Chemical compound C1=C2OC(Cl)OC2=CC2=NC(F)(F)N=C21 RMZRQZISNPQWEM-UHFFFAOYSA-N 0.000 claims description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000004149 thio group Chemical group *S* 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 4
- 125000005291 haloalkenyloxy group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- 125000005108 alkenylthio group Chemical group 0.000 claims description 3
- 125000005109 alkynylthio group Chemical group 0.000 claims description 3
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 3
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 description 38
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 25
- 125000001246 bromo group Chemical group Br* 0.000 description 22
- 150000003254 radicals Chemical class 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- 239000000203 mixture Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 4
- 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 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000005203 haloalkylcarbonyloxy group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 3
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 2
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 2
- NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical compound C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000005336 allyloxy group Chemical group 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 239000012973 diazabicyclooctane Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000005191 hydroxyalkylamino group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 230000003641 microbiacidal effect Effects 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 125000000177 propargylthio group Chemical group [H]C#CC([H])([H])S* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- RWHYUTSGEJYTMQ-UHFFFAOYSA-N 2,4-dibromo-5-methyl-1h-imidazole Chemical compound CC=1NC(Br)=NC=1Br RWHYUTSGEJYTMQ-UHFFFAOYSA-N 0.000 description 1
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
- VECOGDZPSCQNII-UHFFFAOYSA-N 3,5-dimethyl-2h-1,2-oxazole-3-sulfonyl chloride Chemical compound CC1=CC(C)(S(Cl)(=O)=O)NO1 VECOGDZPSCQNII-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 150000003868 ammonium compounds Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- BLHUAXIDWCQEPL-UHFFFAOYSA-M dibenzyl(dimethyl)azanium;methyl sulfate Chemical compound COS([O-])(=O)=O.C=1C=CC=CC=1C[N+](C)(C)CC1=CC=CC=C1 BLHUAXIDWCQEPL-UHFFFAOYSA-M 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 125000000232 haloalkynyl group Chemical group 0.000 description 1
- 125000005292 haloalkynyloxy group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- LQERIDTXQFOHKA-UHFFFAOYSA-N nonadecane Chemical compound CCCCCCCCCCCCCCCCCCC LQERIDTXQFOHKA-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- SDSMZSUWTYFEBO-UHFFFAOYSA-M tributyl(methyl)phosphanium;bromide Chemical compound [Br-].CCCC[P+](C)(CCCC)CCCC SDSMZSUWTYFEBO-UHFFFAOYSA-M 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Definitions
- the present invention relates to a new process for the production of known sulfonylimidazole derivatives which can be used as active ingredients with microbicidal properties.
- sulfonyl imidazole derivatives can be synthesized by reacting imidazole derivatives with sulfonyl halides in the presence of an acid binder and in the presence of a ner thinner (cf. WO
- R 1 and R 2 are the same or different and are independently hydrogen, halogen, cyano, thiocyanato, nitro, formyl, carboxy, carbamoyl, thiocarbamoyl, alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkenyl,
- Q represents oxygen or sulfur and the atoms marked with (*) are each connected to R 3 ,
- n 0, 1 or 2
- R 3 represents optionally substituted aryl or optionally substituted heterocyclyl
- R ⁇ R 5 , R 6 and R 7 independently of one another for hydrogen, halogen, cyano, nitro, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfonyl, alkylsulfonyl, haloalkylsulfonyl, optionally substituted cycloalkyl, hydroxycarbonyl, alkylcarbonyl,
- Z 1 stands for a direct bond, for -CH 2 -, O, S, SO, SO 2 , or CO or
- R 4 and R 5 , or R 5 and R 6 , or R 6 and R 7 each together represent an optionally substituted alkylene chain with 3 or 4 links, in which one or two (non-adjacent) carbon atoms can be replaced by oxygen atoms,
- R for alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkenyl, haloalkenyl, alkenyloxy, alkenylthio, alkynyl, alkynyloxy, alkynylthio, alkylamino, dialkylamino, optionally substituted aryl, optionally substituted aryloxy, optionally substituted
- Arylthio optionally substituted cycloalkyl, optionally substituted cycloalkyloxy, optionally substituted cycloalkylthio, optionally substituted cycloalkylamino, optionally substituted di-cycloalkylamino or represents an optionally substituted, saturated or unsaturated heterocyclic radical and
- X represents fluorine, chlorine or bromine
- R 1 , R 2 and X have the meanings given above, with sulfonyl chlorides
- 2-position carry a halogen atom are at least partially hydrolyzed in the presence of water and a phase transfer catalyst (cf. Houben-Weyl "Methods of Organic Chemistry", Volume E8c, page 365, Georg Thieme Verlag, Stuttgart, New York 1994 and Ind. J. Chem. 26 B, (1987) 985-986). Contrary to expectations, the implementation according to the invention is not adversely affected by such hydrolysis. It is also surprising that the target products are obtained in a significantly higher yield than according to the previously known methods.
- the ner driving according to the invention is characterized by a number of advantages. It enables the synthesis of sulfonylimidazole derivatives of the formula (I) in extremely high yield and excellent purity. It is also favorable that the implementation of the reaction and the isolation of the reaction products do not occur
- the method according to the invention can also be easily transferred to the industrial scale.
- Formula (II) provides a general definition of the imidazole derivatives required as starting materials when carrying out the process according to the invention. These imidazole derivatives can exist in the following two tautomeric forms.
- Preferred starting materials for carrying out the process according to the invention are imidazole derivatives of the formula (II) in which R 1 and R 2 are the same or different and are independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, thiocyanato, nitro, formyl, carboxy, carbamoyl, thiocarbamoyl, alkyl having 1 to 4 carbon atoms, alkoxy
- Halogen atoms dialkylamino with 1 to 4 carbon atoms in each alkyl group, alkylcarbonyl with 1 to 4 carbon atoms in the alkyl part, alkoximinoalkyl with 1 to 4 carbon atoms in the alkoxy part and 1 to 4 carbon atoms in the alkyl part, alkylcarbonyloxy with 1 to 4 carbon atoms in the alkyl part, haloalkylcarbonyloxy with 1 to 4 carbon atoms in the haloalkyl group and 1 to 5 identical or different halogen atoms, alkylthio with 1 to 4 carbon atoms, alkylsulfinyl with 1 to 4 carbon atoms, alkylsulfonyl with 1 to 4 carbon atoms, alkenyl with
- Q oxygen or sulfur
- n 0, 1 or 2
- R 3 is an unsaturated heterocyclyl radical with 5 or 6 ring members and 1 to 3
- Heteroatoms such as nitrogen, oxygen and / or sulfur, it being possible for these radicals to be substituted once to three times, identically or differently, by halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 up to 5 identical or different halogen atoms, haloalkoxy with 1 to 4
- X represents chlorine or bromine.
- Preferred starting materials for carrying out the process according to the invention are also imidazole derivatives of the formula
- R 4 , R 5 , R 6 and R 7 independently of one another are hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, straight-chain or branched alkyl having 1 to 8 carbon atoms, straight-chain or branched haloalkyl having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, straight-chain or branched alkoxy with 1 to 8 carbon atoms, straight-chain or branched haloalkoxy with 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, straight-chain or branched alkylthio with 1 to 8 carbon atoms, straight-chain or branched haloalkylthio with 1 up to 6 carbon atoms and 1 to 13 identical or different halogen atoms, straight-chain or branched alkylsulfinyl with 1 to 8 carbon atoms, straight-chain or branched haloalkylsulfinyl with
- haloalkylsulfonyl having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, optionally one to five times, identical or different by halogen and / or alkyl having 1 to 4
- R 8 represents aryl having 6 to 10 carbon atoms, where each of these radicals can be substituted once to three times, identically or differently by halogen, cyano, nitro, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 up to 4 carbon atoms, haloalkyl with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, haloalkoxy with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, haloalkylthio with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms,
- R 8 also for an unsaturated heterocyclyl radical with 5 or 6 ring members and 1 to 3 heteroatoms, such as nitrogen, oxygen and / or
- Sulfur is, where these radicals can be monosubstituted to trisubstituted, identical or different, by halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, Haloalkoxy with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, alkoxycarbonyl with 1 to 3 carbon atoms in the alkoxy part, cycloalkyl with 3 to 6 carbon atoms, cyano and / or nitro,
- Z 1 stands for a direct bond and for -CH 2 -, O, S, SO, SO ⁇ or CO, or
- R 4 and R 5 , or R 5 and R 6 , or R 6 and R 7 each together for an optionally single to six times by halogen, alkyl having 1 to 4 carbon atoms and / or haloalkyl having 1 to 4 carbon atoms and 1 to 9 halogen atoms are substituted alkylene chain with 3 or 4 links, in which one or two (non-adjacent) carbon atoms can be replaced by oxygen atoms, and
- X represents chlorine or bromine.
- Particularly preferred starting materials for carrying out the process according to the invention are imidazole derivatives of the formula (II) in which
- R 1 and R 2 independently of one another for hydrogen, fluorine, chlorine, bromine, iodine, cyano, thiocyanato, nitro, formyl, carboxy, carbamoyl, thiocarbamoyl, methyl, ethyl, n- or i-propyl, n-, i-, s - or t-butyl, mefhoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylthiohio, trifluoromethylthio trifluoromethylsulphinyl or Trifluormefhylsulfony
- Q oxygen or sulfur
- n 0, 1 or 2
- R represents phenyl or naphthyl, where each of these radicals can be monosubstituted to triple, identical or differently substituted by fluorine, chlorine, bromine, cyano, nitro, formyl, carbamoyl, thiocarbamoyl, methyl, ethyl, n- or i-propyl, n -, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulfmyl, ethylsulfinyl, methylsulfonyl or ethylsulfonyl, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoro- methoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio,
- Methoximinomethyl emoximinomethyl, methoximinoethyl or ethoximinoethyl, cyclopropyl, cyclobutyl, cyclopentyl and / or cyclohexyl,
- R represents an unsaturated heterocyclyl radical with 5 or 6 ring members and 1 to 3
- Heteroatoms such as nitrogen, oxygen and / or sulfur, where each of these radicals can be substituted once or twice, in the same or different manner, by fluorine, chlorine, bromine, methyl, ethyl, methoxy, ethoxy, haloalkyl having 1 or 2 carbon atoms and 1 up to 5 fluorine, chlorine and / or bromine atoms, haloalkoxy with 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, methoxycarbonyl, ethoxycarbonyl, cycloalkyl with 3 to 6 carbon atoms, cyano and / or nitro,
- X represents chlorine or bromine.
- Particularly preferred starting materials when carrying out the process according to the invention are also imidazole derivatives of the formula
- R 4 , R 5 , R 6 and R 7 independently of one another are hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, straight-chain or branched alkyl having 1 to 6 carbon atoms, haloalkyl having 1 or 2 carbon atoms and 1 to 5 fluorine , Chlorine and / or bromine atoms, straight-chain or branched alkoxy with 1 up to 6 carbon atoms, haloalkoxy with 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, straight-chain or branched alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, straight-chain or branched alkylsulfinyl with 1 to 6 carbon atoms,
- Methyl and / or ethyl substituted cycloalkyl with 3 to 6 carbon atoms for hydroxy carbonyl, alkylcarbonyl with 1 to 4 carbon atoms in the straight-chain or branched alkyl part, alkoxycarbonyl with 1 to 4 carbon atoms in the straight-chain or branched alkoxy part, cycloalkylcarbonyl with 3 to 6 carbon atoms in the Cycloalkyl part, cycloalkoxycarbonyl having 3 to 6 carbon atoms in the cycloalkyl part or for -Z * -R 8 , in which
- phenyl which can be monosubstituted to triple, identical or differently substituted by fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl,
- Z 1 stands for a direct bond and for CH 2 , O, S, SO, SO or CO, or
- R 4 and R 5 , or R 5 and R 6 , or R 6 and R 7 each together represent an alkylene chain with 3 or 4 links, optionally substituted up to six times by fluorine, chlorine, methyl and / or trifluoromethyl, in which one or two (not adjacent) carbon atoms can be replaced by oxygen,
- R 4 , R 5 , R 6 and R 7 independently of one another for hydrogen, fluorine, chlorine, bromine, cyano, nitro, for methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl .
- R 8 represents phenyl, which can be monosubstituted to triple, identical or differently substituted by fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n- or i-propyl, n-, i-, s- or t -Butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, difluoromethylthio, trifluoromethylethyl sulfon . or
- Z 1 stands for a direct bond and for CH2, O, S, SO, SO2 or CO, or
- R 4 and R 5 , or R 5 and R 6 , or R 6 and R 7 each together for the groups -CF2-O-CF2-, -O-CF 2 -O-, -O-CF2-CHF-O- , -O-CHF-CHF-O-, -O-CF 2 -CF2-O-, -O-CF2-CFCI-O- or -O-CFC1-CFC1-O-,
- the imidazole derivatives of the formula (LT) are known or can be prepared by known processes (cf. WO 97-06 171, WO 97-47 620, EP-A 0 893 445, DE-A 198 29 740 and JP-A 54-90 175).
- Formula (HI) provides a general definition of the sulfonyl chlorides which are further required as starting materials when carrying out the process according to the invention.
- R represents straight-chain or branched alkyl having 1 to 4 carbon atoms, straight-chain or branched haloalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, straight-chain or branched alkoxy having 1 to 4 carbon atoms, straight-chain or branched haloalkoxy having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, straight-chain or branched alkylthio having 1 to 4 carbon atoms, straight-chain or branched haloalkylthio having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, straight-chain or branched alkenyl having 2 to 4 carbon atoms, straight-chain or branched haloalkenyl with 2 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, straight-chain or branched alkenyloxy with 2 to 4 carbon atoms, straight-chain or branched alken
- R represents phenyl, phenoxy or phenylthio, where each of these radicals can be substituted once to three times, identically or differently, by fluorine, Chlorine, bromine, alkyl with 1 to 4 carbon atoms, haloalkyl with 1 to 4 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, alkoxy with 1 to 4 carbon atoms and / or haloalkoxy with 1 to 4 carbon atoms and 1 to 5 Fluorine, chlorine and / or bromine atoms,
- Morpholinyl where each of the abovementioned radicals can be substituted once to three times, in the same way or differently, by fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms and / or haloalkyl having 1 to 4 carbon atoms and 1 to 5 fluorine, chlorine, and / or bromine atoms,
- R represents an unsaturated heterocyclyl radical with 5 or 6 ring members and 1 to 3 heteroatoms, such as nitrogen, oxygen and / or sulfur, it being possible for these radicals to be monosubstituted to trisubstituted, identical or different, by halogen, cyano, nitro, hydroxyl, Amino, formyl, carboxy, carbamoyl, thiocarbamoyl, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, haloalkyl with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, haloalkoxy with 1 to 4 carbon atoms and 1 to 5 same or different halogen atoms,
- Particularly preferred starting materials are sulfonyl chlorides of the formula (III), in which
- R is methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, methylthio, ethylthio, n- or i-propylthio, difluoromethylthio, trifluoromethylthio, difluorochloromethylthio, allyl, n- or s-butenyl; Allyloxy, n- or s-butenyloxy; Allylthio, n- or s-butenylthio; Propargyl, n- or s-butinyl; propargyloxy; prop
- R represents phenyl, phenoxy or phenylthio, where each of these radicals can be monosubstituted to triple, identical or differently substituted by fluorine, chlorine, bromine, methyl, ethyl, n- or i-propyl, methoxy, ethoxy, n- or i-
- R represents an unsaturated heterocyclyl radical with 5 or 6 ring members and 1 to 3 heteroatoms, such as nitrogen, oxygen and / or sulfur, where each of these radicals can be mono- or disubstituted, identical or differently substituted by fluorine, chlorine, bromine or cyano , Nitro, hydroxy, amino, formyl, carboxy, carbamoyl, thiocarbamoyl, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, haloalkyl with 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, haloalkoxy with 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and / or bromine atoms, alkoxycarbonyl with 1 or 2 carbon atoms in the alkoxy part, cycloalkyl with 3 to 6 carbon atoms, haloalkylsulfinyl with 1 or 2 carbon atoms and 1 to
- R is methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n- or i-propoxy, n-, i-, s- or t-butoxy,
- R represents phenyl, phenoxy or phenylthio, where each of these radicals can be substituted once to three times, identically or differently, by fluorine,
- R stands for cyclopropyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclopentyloxy, cyclohexyloxy, cyclopropylthio, cyclopentylthio, cyclohexylthio, cyclopropylamino, cyclopentylamino, cyclohexylamino, 1-pyrrolidinyl, 1-piperidinyl or 1-each of these morpholinyls, simply being where bis-morpholinyl, , may be substituted identically or differently by fluorine, chlorine, bromine, methyl, ethyl, n- or i-propyl and / or trifluoromethyl,
- the sulfonyl chlorides of the formula (III) are known or can be prepared by known methods (cf. WO 97-06 171, WO 97-47 620 and DE-A 198 29 740).
- Suitable acid binders when carrying out the process according to the invention are preferably alkaline earth metal or alkali metal hydroxides, acetates, carbonates or bicarbonates.
- alkaline earth metal or alkali metal hydroxides, acetates, carbonates or bicarbonates examples include sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, calcium acetate, sodium carbonate, potassium carbonate, potassium hydrogen carbonate.
- Ammonium compounds and organic bases such as ammonium acetate or ammonium carbonate, or tertiary amines, such as trimethylamine, triethylamine, tri-butylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine , N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or diazabicycloundecene (DBU).
- DABCO diazabicyclooctane
- DBN diazabicyclonones
- DBU diazabicycloundecene
- Suitable diluents for carrying out the process according to the invention are all customary organic solvents which are not very miscible with water.
- Aliphatic, alicyclic or aromatic hydrocarbons such as petroleum, hexane, heptane, cyclohexane, methylcyclohexane, are preferably usable.
- halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane
- further ethers such as diethyl ether, diis
- Suitable phase transfer catalysts for carrying out the process according to the invention are all reaction accelerators which can normally be used for this purpose.
- Tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tributyl-methylphosphonium bromide can preferably be used, alkylammonium bromide, dibenzyl-dimethyl-ammonium methyl sulfate, dimethyl-C 12 / C 14-alkyl-benzylammonium chloride, dimethyl-C 1 2 / C 1 4 -alkyl-benzylammonium bromide, tetrabutylammonium hydroxide, triethylbenzylammonium chloride, methyl-trioctylchlorobenzylammonium chloride, Crown-5, 18-
- reaction temperatures can be varied within a substantial range when carrying out the process according to the invention. In general, temperatures between 0 ° C and 130 ° C, preferably between 20 ° C and 50 ° C.
- the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to work under increased or reduced pressure.
- an equivalent amount or also an excess of sulfonyl chloride of the formula (III) and an equivalent amount or also an excess of acid binder are generally employed per mole of imidazole derivative of the formula (II).
- the processing takes place according to usual methods. In general, the procedure is such that the organic phase is separated off, the aqueous phase is extracted with an organic solvent which is not very miscible with water, the combined organic phases are washed if necessary, then dried and concentrated. However, it is also possible to work up without adding water by filtering off the resulting solids of the formula (I). Any impurities that may still be present can be removed according to the usual methods Methods, such as by recrystallization or by chromatographic means, are separated.
- the sulfonylimidazole derivatives of the formula (I) which can be prepared by the process according to the invention are known as active ingredients with microbicidal, in particular fungicidal, properties (cf. WO 97-06 171, WO 97-47 620 and DE-A 198 29 740) ,
- the metering pump is rinsed with 2 kg of toluene and the rinsing liquid is added to the reaction mixture. After stirring for three hours at temperatures between 20 ° C and 30 ° C, the reaction mixture is filtered. The filter residue is washed three times with 200 kg of water each and then dried at 40 to 50 ° C under reduced pressure.
- a total of 132 kg of a product is obtained from the three batches, 94% of which consists of l- (3,5-dimethyl-isoxazole-4-sulfonyl) -2-chloro-6,6-difluoro- [1,3] -dioxolo - [4,5-f] -benz-imidazole exists.
- the yield is then calculated to be 66% of theory.
- the mother liquor contains a further 38 kg of l- (3,5-dimethyl-isoxazole-4-sulfonyl) -2-chloro-6,6-difluoro- [1,3] -dioxolo- [4,5-f] - Contain benzimidazole, which corresponds to an additional yield of 20% of theory.
- Comparative example A
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10005278 | 2000-02-07 | ||
| DE10005278A DE10005278A1 (de) | 2000-02-07 | 2000-02-07 | Verfahren zur Herstellung von Sulfonyl-imidazol-Derivaten |
| PCT/EP2001/000794 WO2001057043A1 (de) | 2000-02-07 | 2001-01-25 | Verfahren zur herstellung von sulfonyl-imidazol-derivaten mittels phasentransfer-katalyse |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1265902A1 true EP1265902A1 (de) | 2002-12-18 |
Family
ID=7630062
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP01916951A Withdrawn EP1265902A1 (de) | 2000-02-07 | 2001-01-25 | Verfahren zur herstellung von sulfonyl-imidazol-derivaten mittels phasen-transfer-katalyse |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20030040630A1 (OSRAM) |
| EP (1) | EP1265902A1 (OSRAM) |
| JP (1) | JP2003522179A (OSRAM) |
| AU (1) | AU2001244107A1 (OSRAM) |
| DE (1) | DE10005278A1 (OSRAM) |
| IN (1) | IN188923B (OSRAM) |
| WO (1) | WO2001057043A1 (OSRAM) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5400261B2 (ja) * | 2004-11-25 | 2014-01-29 | 日産化学工業株式会社 | インドール化合物の製造方法 |
| AU2021382384A1 (en) * | 2020-11-23 | 2023-03-23 | F. Hoffmann-La Roche Ag | New process for the manufacture of tetrazole derivatives |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD241412A1 (de) * | 1985-10-02 | 1986-12-10 | Univ Halle Wittenberg | Verfahren zur herstellung von n-sulfonyl-iminokohlensaeure-alkylester-dialkylamiden |
| HUP9802822A3 (en) * | 1995-08-10 | 1999-04-28 | Bayer Ag | Halobenzimidazol derivatives, intermediates, preparation thereof and microbocide compositions containing these compounds as active ingredients |
| DE19623207A1 (de) * | 1996-06-11 | 1997-12-18 | Bayer Ag | Imidazolderivate |
| DE19745692A1 (de) * | 1997-07-24 | 1999-01-28 | Bayer Ag | Verfahren zur Herstellung von 2-Chlor-benzimidazol-Derivaten |
| WO1999005116A1 (de) * | 1997-07-24 | 1999-02-04 | Bayer Aktiengesellschaft | Nitrophenyl-sulfonyl-imidazole und deren verwendung zur bekämpfung von pflanzlichen und tierischen schädlingen |
-
2000
- 2000-02-07 DE DE10005278A patent/DE10005278A1/de not_active Withdrawn
-
2001
- 2001-01-24 IN IN80MU2001 patent/IN188923B/en unknown
- 2001-01-25 WO PCT/EP2001/000794 patent/WO2001057043A1/de not_active Application Discontinuation
- 2001-01-25 US US10/182,965 patent/US20030040630A1/en not_active Abandoned
- 2001-01-25 JP JP2001557874A patent/JP2003522179A/ja active Pending
- 2001-01-25 AU AU2001244107A patent/AU2001244107A1/en not_active Abandoned
- 2001-01-25 EP EP01916951A patent/EP1265902A1/de not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0157043A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2003522179A (ja) | 2003-07-22 |
| US20030040630A1 (en) | 2003-02-27 |
| IN188923B (OSRAM) | 2002-11-23 |
| DE10005278A1 (de) | 2001-08-09 |
| AU2001244107A1 (en) | 2001-08-14 |
| WO2001057043A8 (de) | 2001-11-15 |
| WO2001057043A1 (de) | 2001-08-09 |
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