MXPA98005645A - N-arylsulfilimine compounds and their use as catalysts in the preparation of n-arylarylsulfonamide compounds - Google Patents
N-arylsulfilimine compounds and their use as catalysts in the preparation of n-arylarylsulfonamide compoundsInfo
- Publication number
- MXPA98005645A MXPA98005645A MXPA/A/1998/005645A MX9805645A MXPA98005645A MX PA98005645 A MXPA98005645 A MX PA98005645A MX 9805645 A MX9805645 A MX 9805645A MX PA98005645 A MXPA98005645 A MX PA98005645A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- compound
- triazolo
- formula
- aromatic
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 120
- 239000003054 catalyst Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims description 36
- -1 aromatic sulfonyl chloride compounds Chemical class 0.000 claims abstract description 152
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 12
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical compound S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 106
- 229910052801 chlorine Inorganic materials 0.000 claims description 53
- 229910052794 bromium Inorganic materials 0.000 claims description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 44
- 229910052731 fluorine Inorganic materials 0.000 claims description 42
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 40
- 229910052717 sulfur Inorganic materials 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 29
- 125000003342 alkenyl group Chemical group 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 229910052740 iodine Inorganic materials 0.000 claims description 22
- 201000002674 obstructive nephropathy Diseases 0.000 claims description 20
- YBBRCQOCSYXUOC-UHFFFAOYSA-N Sulfuryl chloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 16
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 16
- SMWDFEZZVXVKRB-UHFFFAOYSA-N quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-Methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 235000005152 nicotinamide Nutrition 0.000 claims description 5
- 239000011570 nicotinamide Substances 0.000 claims description 5
- 229960003966 nicotinamide Drugs 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 230000003197 catalytic Effects 0.000 claims description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 3
- ZLKWIPGKQOYHSY-UHFFFAOYSA-N 5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonyl chloride Chemical compound N1=C(C)C=CN2N=C(S(Cl)(=O)=O)N=C21 ZLKWIPGKQOYHSY-UHFFFAOYSA-N 0.000 claims description 2
- MRYRRTMVGNLFNC-UHFFFAOYSA-N 8-chloro-5-methoxy-[1,2,4]triazolo[1,5-a]pyridine-2-sulfonyl chloride Chemical compound COC1=CC=C(Cl)C2=NC(S(Cl)(=O)=O)=NN12 MRYRRTMVGNLFNC-UHFFFAOYSA-N 0.000 claims description 2
- 229910005948 SO2Cl Inorganic materials 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- VEQWDHZZNKYRKB-UHFFFAOYSA-N 5-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridine-2-sulfonyl chloride Chemical compound COC1=CC(C)=CC2=NC(S(Cl)(=O)=O)=NN12 VEQWDHZZNKYRKB-UHFFFAOYSA-N 0.000 claims 1
- LSZZFHSZXLBXIL-UHFFFAOYSA-N 5-methoxy-7-methyl-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonyl chloride Chemical compound COC1=NC(C)=CC2=NC(S(Cl)(=O)=O)=NN12 LSZZFHSZXLBXIL-UHFFFAOYSA-N 0.000 claims 1
- ORPWCYLOEPEKCR-UHFFFAOYSA-N 8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonyl chloride Chemical compound COC1=NC=C(F)C2=NC(S(Cl)(=O)=O)=NN12 ORPWCYLOEPEKCR-UHFFFAOYSA-N 0.000 claims 1
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 1
- LNDCSJHELOGTGE-UHFFFAOYSA-N 5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonyl chloride Chemical compound CCOC1=NC(F)=CC2=NC(S(Cl)(=O)=O)=NN12 LNDCSJHELOGTGE-UHFFFAOYSA-N 0.000 abstract description 7
- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 abstract description 5
- QNXAVFXEJCPCJO-UHFFFAOYSA-N Diclosulam Chemical compound N=1N2C(OCC)=NC(F)=CC2=NC=1S(=O)(=O)NC1=C(Cl)C=CC=C1Cl QNXAVFXEJCPCJO-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
- 239000000203 mixture Substances 0.000 description 58
- 238000003756 stirring Methods 0.000 description 57
- 238000001816 cooling Methods 0.000 description 45
- 239000007787 solid Substances 0.000 description 45
- 239000000460 chlorine Substances 0.000 description 42
- 239000000243 solution Substances 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- WEVYAHXRMPXWCK-FIBGUPNXSA-N 2,2,2-trideuterioacetonitrile Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- QMMFVYPAHWMCMS-UHFFFAOYSA-N methyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 150000004982 aromatic amines Chemical class 0.000 description 7
- BXRYSXCIRIKKJV-UHFFFAOYSA-N methyl 2-amino-6-chlorobenzoate Chemical compound COC(=O)C1=C(N)C=CC=C1Cl BXRYSXCIRIKKJV-UHFFFAOYSA-N 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- ODUZJBKKYBQIBX-UHFFFAOYSA-N 2,6-difluoroaniline Chemical compound NC1=C(F)C=CC=C1F ODUZJBKKYBQIBX-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- AKEJUJNQAAGONA-UHFFFAOYSA-N Sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N Trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- 238000002211 ultraviolet spectrum Methods 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002363 herbicidal Effects 0.000 description 3
- MSXSZFYRADEEJA-UHFFFAOYSA-N methyl 2-amino-3-chlorobenzoate Chemical compound COC(=O)C1=CC=CC(Cl)=C1N MSXSZFYRADEEJA-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000004434 sulfur atoms Chemical group 0.000 description 3
- NCYNKWQXFADUOZ-UHFFFAOYSA-N 1,1-dioxo-2,1$l^{6}-benzoxathiol-3-one Chemical compound C1=CC=C2C(=O)OS(=O)(=O)C2=C1 NCYNKWQXFADUOZ-UHFFFAOYSA-N 0.000 description 2
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N Benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N Chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- 229940093912 Gynecological Sulfonamides Drugs 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229940079867 intestinal antiinfectives Sulfonamides Drugs 0.000 description 2
- 230000004301 light adaptation Effects 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atoms Chemical group N* 0.000 description 2
- 229940005938 ophthalmologic antiinfectives Sulfonamides Drugs 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- WJJBIYLGJUVNJX-UHFFFAOYSA-N pyrimidine-2-sulfonamide Chemical compound NS(=O)(=O)C1=NC=CC=N1 WJJBIYLGJUVNJX-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- NBNBICNWNFQDDD-UHFFFAOYSA-N sulfuryl dibromide Chemical class BrS(Br)(=O)=O NBNBICNWNFQDDD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 229940026752 topical Sulfonamides Drugs 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VENMDXUVHSKEIN-UTLUCORTSA-N (2S)-2-[[(2S)-2-[[(2R)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(N)=NCCC[C@@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VENMDXUVHSKEIN-UTLUCORTSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 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
- HWIVGBQUEUPWHG-UHFFFAOYSA-N 1-thia-2,3-diazacyclopent-2-en-4-yne Chemical group S1N=NC#C1 HWIVGBQUEUPWHG-UHFFFAOYSA-N 0.000 description 1
- ZOCCDAJTQGGXAG-UHFFFAOYSA-N 1H-triazolo[1,5-c]pyrimidine-2-sulfonamide Chemical compound C1=NC=CC2=CN(S(=O)(=O)N)NN21 ZOCCDAJTQGGXAG-UHFFFAOYSA-N 0.000 description 1
- LBJZNWGDORSXJS-UHFFFAOYSA-N 1H-triazolo[1,5-c]pyrimidine-2-sulfonic acid Chemical compound C1=NC=CC2=CN(S(=O)(=O)O)NN21 LBJZNWGDORSXJS-UHFFFAOYSA-N 0.000 description 1
- NATVSFWWYVJTAZ-UHFFFAOYSA-N 2,4,6-trichloroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1Cl NATVSFWWYVJTAZ-UHFFFAOYSA-N 0.000 description 1
- RWJDANBKQBNXSN-UHFFFAOYSA-N 2,5-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=C(C)C=CN2N=C(C)N=C21 RWJDANBKQBNXSN-UHFFFAOYSA-N 0.000 description 1
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- SNNFWLRRGFJXOE-UHFFFAOYSA-N 2-chloro-4-propan-2-yloxypyridin-3-amine Chemical compound CC(C)OC1=CC=NC(Cl)=C1N SNNFWLRRGFJXOE-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- RGYOYFIMSWZBKB-UHFFFAOYSA-N 2-methoxy-6-(trifluoromethyl)phenol Chemical compound COC1=CC=CC(C(F)(F)F)=C1O RGYOYFIMSWZBKB-UHFFFAOYSA-N 0.000 description 1
- FCMRHMPITHLLLA-UHFFFAOYSA-N 2-methyl-6-nitroaniline Chemical compound CC1=CC=CC([N+]([O-])=O)=C1N FCMRHMPITHLLLA-UHFFFAOYSA-N 0.000 description 1
- ZMPRRFPMMJQXPP-UHFFFAOYSA-N 2-sulfobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1S(O)(=O)=O ZMPRRFPMMJQXPP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-Methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 1
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-Methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 1
- ODFDZOQJRPDQDF-UHFFFAOYSA-N 4-bromo-2-methylpyrazol-3-amine Chemical compound CN1N=CC(Br)=C1N ODFDZOQJRPDQDF-UHFFFAOYSA-N 0.000 description 1
- SEWNAJIUKSTYOP-UHFFFAOYSA-N 4-chloro-3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=CC=C1Cl SEWNAJIUKSTYOP-UHFFFAOYSA-N 0.000 description 1
- VSVXOFAFPAPGNS-UHFFFAOYSA-N 4-chloro-N-(2,6-difluorophenyl)benzenesulfonamide Chemical compound FC1=CC=CC(F)=C1NS(=O)(=O)C1=CC=C(Cl)C=C1 VSVXOFAFPAPGNS-UHFFFAOYSA-N 0.000 description 1
- RBVWYRXVVWQTTI-UHFFFAOYSA-N 4-chloro-N-(2-methyl-6-nitrophenyl)-3-nitrobenzenesulfonamide Chemical compound CC1=CC=CC([N+]([O-])=O)=C1NS(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 RBVWYRXVVWQTTI-UHFFFAOYSA-N 0.000 description 1
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
- RKQZHGLRHBTDTP-UHFFFAOYSA-N 5,7-dimethoxy-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonyl chloride Chemical compound N1=C(OC)C=C(OC)N2N=C(S(Cl)(=O)=O)N=C21 RKQZHGLRHBTDTP-UHFFFAOYSA-N 0.000 description 1
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
- SZEFAGSXNXVNDB-UHFFFAOYSA-N 5-ethoxy-2-[(5-ethoxy-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)disulfanyl]-7-fluoro-[1,2,4]triazolo[1,5-c]pyrimidine Chemical compound N1=C2C=C(F)N=C(OCC)N2N=C1SSC1=NN2C(OCC)=NC(F)=CC2=N1 SZEFAGSXNXVNDB-UHFFFAOYSA-N 0.000 description 1
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1H-pyrazole Chemical compound CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N Butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- QYGUSXVMTGMSFW-UHFFFAOYSA-N C(C)OC1=NC=2N(C(=C1)C)N=C(N2)S(=O)(=O)Cl Chemical compound C(C)OC1=NC=2N(C(=C1)C)N=C(N2)S(=O)(=O)Cl QYGUSXVMTGMSFW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate dianion Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- NHOWDZOIZKMVAI-UHFFFAOYSA-N Fenarimol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 description 1
- 102100009854 MID1 Human genes 0.000 description 1
- 101700079340 MID1 Proteins 0.000 description 1
- DADSZOFTIIETSV-UHFFFAOYSA-N N,N-dichloroaniline Chemical compound ClN(Cl)C1=CC=CC=C1 DADSZOFTIIETSV-UHFFFAOYSA-N 0.000 description 1
- WHFAKELBPYBZRJ-UHFFFAOYSA-N N-(2,6-dichlorophenyl)-7-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide Chemical compound N=1N2C(OC)=NC(F)=CC2=NC=1S(=O)(=O)NC1=C(Cl)C=CC=C1Cl WHFAKELBPYBZRJ-UHFFFAOYSA-N 0.000 description 1
- NVEMIOGUKOYSHZ-UHFFFAOYSA-N N-(2,6-difluorophenyl)-8-fluoro-N-[(8-fluoro-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)sulfonyl]-5-methoxy-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide Chemical compound N=1N2C(OC)=NC=C(F)C2=NC=1S(=O)(=O)N(S(=O)(=O)C1=NN2C(OC)=NC=C(F)C2=N1)C1=C(F)C=CC=C1F NVEMIOGUKOYSHZ-UHFFFAOYSA-N 0.000 description 1
- GOEWZPICEGNTPR-UHFFFAOYSA-N N-(2-chlorophenyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC=C1Cl GOEWZPICEGNTPR-UHFFFAOYSA-N 0.000 description 1
- DJVKPXCLNPLPPI-UHFFFAOYSA-N N-(5-bromopyrimidin-2-yl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=NC=C(Br)C=N1 DJVKPXCLNPLPPI-UHFFFAOYSA-N 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N Sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N Tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- ZSTJFLDTAMURNS-UHFFFAOYSA-N [SH2]=Nc1ccccc1 Chemical class [SH2]=Nc1ccccc1 ZSTJFLDTAMURNS-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001010 compromised Effects 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001627 detrimental Effects 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 229940064982 ethylnicotinate Drugs 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- CYDFZRJJVXDMIK-UHFFFAOYSA-N methyl 3-chloro-2-[(dimethyl-$l^{4}-sulfanylidene)amino]benzoate Chemical compound COC(=O)C1=CC=CC(Cl)=C1N=S(C)C CYDFZRJJVXDMIK-UHFFFAOYSA-N 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N methylsulfanylbenzene Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- BYBCSHJGFWTWAB-UHFFFAOYSA-N pyrimidine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=NC=CC=N1 BYBCSHJGFWTWAB-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 229960001663 sulfanilamide Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
N-arylsulfilimine compounds, such as S,S-dimethyl-N-(2,6-dichlorophenyl)sulfilimine, were prepared and found to catalyze the reaction of aromatic sulfonyl chloride compounds, such as 2-chlorosulfonyl-7-fluoro-5-ethoxy[1,2,4]-triazolo[1,5-c]pyrimidine, with aromatic amine compounds, such as 2,6-dichloroaniline, to form N-arylarylsulfonamide compounds, such as N-(2, 6-dichlorophenyl)-7-fluoro-5-ethoxy-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide. The aryl moiety of the N-arylsulfilimine catalyst and the aryl moiety of the aromatic amine compound were generally chosen to be identical.
Description
COMPU THESE OF N-ARILSULFILIMINE AND ITS USE AS CATALYSTS IN THE PREPARATION OF COMPOUNDS OF N-AR1LARILSU LFONAMIDA
The present invention relates to the use of N-aryl sulphimymine compounds as catalysts in the reaction of aromatic sulfonyl chloride compounds with aromatic amines to form N-arylarylsulfonamide compounds and to novel N-arylsulphimycin compounds. The preparation of N-arylarylsulfonamide compounds by the
The reaction of aromatic sulfonyl chloride compounds with aromatic amine compounds typically yields unsatisfactory results because the reaction is slow and the yields are poor. The preparation of such compounds wherein the aromatic amine compound and / or the aromatic sulfonyl chloride compound possesses one or,
In particular, two ortho substituents are frequently unsatisfactory in particular due to the steric deactivation effect and, when the substituents are electron withdrawers, the electronic deactivation effect of ortho substituents. Pyridine, picolines and lutidines have long been known to catalyze the reaction of many compounds
of sulfonyl chloride with amines to form sulfonamides. Recently, it was reported that a mixture of a pyridine base and dimethyl sulfoxide gave improved results in many cases (U.S. Patent 5, 177,206). Many N-arylarylsulfonamide compounds are known in the art to be valuable herbicides and methods to obtain them more easily and in improved yields are desirable. A number of substituted N-phenylsulfiimine compounds are known, for example from J. Org. Chem .. 39. 3365-3372 (1974), and the preparation and more of the chemistry of these compounds have been reviewed in the literature, for example, in Russian Chemical Reviews. 59. 819-831
(1990). Certain of these compounds have been reported to be useful intermediates for further synthesis. For example, rearrangement of such compounds having at least one unsubstituted ortho position to obtain 2-alkylthiomethyl-aniline compounds has been reported in U.S. Patent 4,496,765. The use of N-phenylsulfilimine compounds as catalysts for the preparation of sulfonamides has not been reported. It has now been found that N-arylsulfilimine compounds catalyze the reaction of aromatic sulfonyl chloride compounds with aromatic amines to form N-arylarylsulfonamide compounds. The effect is especially important in such reactions involving a relatively unreactive aromatic sulfonyl chloride compound and / or a relatively unreactive aromatic amine compound. Higher reaction rates and improved yields are obtained. The invention includes a process for the preparation of an N-arylarylsulfonamide compound of Formula IV:
Q-SO2NH-AR wherein Q and AR each independently represent a portion of aromatic hydrocarbyl or of aromatic heterocyclyl which comprises combining a sulfonyl chloride compound of Formula I I: Q- -S02CI
wherein Q is as defined above with an amine compound of Formula I I I:
AR- N H2
wherein AR is as defined above in the presence of an aromatic tertiary amine base and a catalytic amount added of an N-arylsulfilimine compound of Formula I:
R / AR'- N = S \ R 'wherein R represents methyl, ethyl or n-propyl; R 'represents R, benzyl or phenyl; or R and R 'together represent tetramethylene; and AR 'represents a portion of aromatic hydrocarbyl or aromatic heterocyclyl.
It is greatly preferred that AR 'in the sulfilimine compound is selected to be identical with AR in the amine compound. The preparation of an N-arylarylsulfonamide compound of Formula IV wherein AR represents a phenyl, pyridinyl, or a 1-alkylpyrazolyl portion optionally having 1 to 3 substituents selected from F, Cl, Br, I, NO2, CN, O (C3 C4 alkenyl), or O (C3-C4 alkynyl); d-C4 alkyl, O (d-C4 alkyl), N (C? -C4 alkyl) 2, S (d-C4 alkyl), SO2 (d-C4 alkyl), CO2 (dC alkyl), CONH (d-C4) alkyl), or CON (d-C4 alkyl) 2 (each alkyl optionally mono to fully substituted with fluorine); or phenyl or phenoxy (each optionally possessing 1 to 3 substituents selected from the group consisting of F, Cl, Br, CN, CF3, NO2, and CH3), is a preferred embodiment of the invention. A process for the preparation of N-arylarylsulfonamide compounds of Formula I I I, wherein AR represents an aromatic portion selected from a) a substituted phenyl portion of the formula:
wherein A represents F, Cl, Br, NO2, CN, C? -C fluoroalkyl, CO2 (C? -C4 alkyl), CONH (C? -C4 alkyl), CON (C? -C4 alkyl) 2, SO2 ( C? -C4 alkyl), or SO2 (C? -C fluoroalkyl);
B represents d-C4 alkyl, F, Cl, Br, 0 (d-C4 alkyl), 0 (d-C4
* fluoroalkyl), S (d-C alkyl), S (d-C4 fluoroalkyl), N (C? -C alkyl) 2; or phenyl, phenoxy or phenylthio each optionally possessing 1 to 3 substituents selected from the group consisting of F, Cl, Br, CN, CF3, N02, and CH3; and D and J each independently represents H or CH3 with the proviso that at least one of D and J represents H; b) a substituted 3-pyridinyl portion of the formula:
wherein 15 L and M each independently represent H, C? -C4 alkyl, dC4 fluoroalkyl, 0 (C1-C4 alkyl), O (dC fluoroalkyl), 0 (C2-C alkoxyalkyl), O (C3-C4 alkenyl), O (C3-C alkynyl), S (C? -C4 alkyl), S (C? -C4 fluoroalkyl), SO2 (d-C4 alkyl), SO2 (d-C4 fluoroalkyl), F, Cl, Br , I, CN, NO2, C6H5, CO2 (C? -C4 alkyl), CO2 (C3-C4 alkenyl), CO2 (C3-C4)
Alkynyl), CON (C? -C4 alkyl) 2, or CONH (C? -C alkyl), with the proviso that not more than one of L and M represents H; and T represents H, F, Cl, Br, I, CH3, or CF3; or c) a portion of 3-, 4- or 5-pyrazolyl substituted with a C1-C3 alkyl group in the 1-position, with at least one Cl, Br, i or CF3, and
Optionally, with an OCH3 or CH3 group are sometimes especially preferred. Such compounds wherein Q represents 5-amino-1, 2,4-triazin-3-yl or a [1, 2,4] triazolo [1, 5-a] pyrimidin-1-yl, [1, 2, 4] triazolo [1, 5-c] pyrimidin-2-i !, or [1, 2,4] triazolo [1, 5-a] pyridin-2-yl each substituted with one or more F, Cl groups, Br, I, C1-C3 alkyl, C1-C3 fluoroalkyl, O (d-C3 alkyl) constitute a class of special interest because the resulting compounds of Formula II I are valuable herbicidal compounds or are intermediates for the preparation of valuable herbicidal compounds . The invention further includes substituted N-arylsulfilimine compounds of Formula I: R / AR'- N = S R 'wherein R represents methyl, ethyl, or n-propyl; R 'represents R, benzyl or phenyl; or R and R 'together represent tetramethylene; and AR 'represents an aromatic portion selected from a) a substituted phenyl portion of the formula:
wherein A represents F, Cl, Br, N02, CN, C? -C4 fluoroalkyl, CO2 (d-C4 alkyl), CON H (d-C4 alkyl), CON (d-C4 alkyl) 2, SO2 (C1- C alkyl), or S02 (C? -C4 fluoroalkyl); B represents d-C4 alkyl, F, Cl, Br, O (dC alkyl), O (d-C4 fluoroalkyl), S (C? -C alkyl), S (C? -C4 fluoroalkyl), N (C? C4 alkyl) 2; or phenyl, phenoxy or phenylthio each optionally possessing 1 to 3 substituents selected from the group consisting of F, Cl, Br, CN, CF3, N02, and CH3; and D and J each independently represents H or CH3 with the proviso that at least one of D and J represents H; c) a substituted 3-pyridinyl portion of the formula:
wherein L and M each independently represent H, C? -C4 alkyl, Ci-C4 fluoroalkyl, O (d-C4 alkyl), O (C1-C fluoroalkyl), O (C2-C4 alkoxyalkyl), O (C3- C alkenyl), O (C3-C4 alkynyl), S (dC alkyl), S (C? -C4 fluoroalkyl), SO2 (C? -C4 alkyl), SO2 (dC fluoroalkyl), F, Cl, Br, I, CN, NO, C6H5, CO2 (d-C4 alkyl), CO2 (C3-C4 alkenyl), CO2 (C3-C4 alkynyl), CON (C? -C alkyl) 2, or CONH (C? -C4 alkyl), with the proviso that no more than one of L and M represents H; and T represents H, F, Cl, Br, I, CH3, or CF3; or c) a 3-, 4- or 5-pyrazolyl portion substituted with a C1-C3 alkyl group in the 1-position, with at least one Cl, Br, I or CF3, and optionally, with an OCH3 or CH3 group. The catalytic N-arylsulfilimine compounds of the invention, which may be represented by Formula I:
/ AR'- N = S \ R '
or, alternatively, through the formula:
- + R / AR'- N- S \ R '
they are characterized by having a nitrogen-sulfur semipolar ligature. This ligature can be shown as a double ligature, the sulfur atom of which is tetravalent as in Formula I, or can be shown as a simple bond, the nitrogen atom of which is negatively charged and the sulfur atom of which is positively charged as in Formula la. Compounds possessing such ligatures are often referred to as ylides. For simplicity, the compounds of the invention are shown herein to be compounds having the structure of Formula I with the understanding that these compounds are the same as the compounds shown.
# for having the structure of Formula la. The substituents on the sulfur atom are R and R ', wherein R represents methyl, ethyl or n-propyl and R' represents R, phenyl, or benzyl; or wherein R and R 'together represent tetramethylene. Such compounds, wherein R and R 'represent both methyl are generally preferred. The portion attached to the nitrogen atom is AR, which represents a portion of aromatic hydrocarbyl or aromatic heterocyclyl. This
* definition is inclusive of all aromatic hydrocarbons and portions of
Aromatic heterocyclyl, whether or not these portions possess substituents. Examples of suitable aromatic hydrocarbyl moieties include phenyl, naphthyl, phenanthrenyl and indenyl. Examples of suitable aromatic heterocyclic portions include pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3,5-triazinyl, quinolinyl,
-quinazolinyl, quinoxalinyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 1,4-oxadiazolyl, 1,4-oxadiazolyl, 1,3-thiadiazolyl, 1,4-thiadiazolyl , 1, 2,4-triazolyl, benzofuranyl, benzo [b] thienyl, indolyl, [1, 2,4] triazolo [1, 5-a] pyrimidinyl, [1, 2,4] triazolo [1, 5-c] ] pyrimidinyl, [1, 2,4] triazolo [1, 5-a] pyridinyl, pyrazolo [1, 5,20 ajpyrimidinyl, and [1, 2,4] triazolo [1, 5-a] [1, 3, 5] triazinyl. AR 'is preferably a substituted phenyl portion, a substituted pyridinyl moiety or a substituted pyrazolyl moiety. Compounds wherein AR 'represents a substituted phenyl or substituted pyridinyl moiety are often of special interest.
The substituents possessed by the hydrocarbyl portions and
# AR aromatic heterocyclyl include any substituent that is stable in the presence of other substituents on the N-arylsulphimymine compound and which does not react with the starting materials used to make the sulphimymine compound. Suitable substituents include F, Cl, Br, I, N02, CN, C? -C8 alkyl, 0 (d-C8 alkyl), 0 (C3-C3 alkenyl), 0 (C3-C8 alkenyl), N (d-) C8 alkyl) 2, S (d-C8 alkyl), S (C3-C8 alkenyl), S (C3-C8 alkenyl), SO2 (C? -8 alkyl), SO2 (C3-C8 alkenyl),
# S02 (C3-C8 alkenyl), CO2 (C? -C8 alkyl), CO2 (C3-C8 alkenyl), CO2 (C3-C8)
alkenyl), CON H (d-C8 alkyl), CON (C? -C8 alkyl) 2, Si (C? -8 alkyl) 3, phenyl, phenoxy, thiophenoxy, pyridinyloxy, and pyridinylthio. Each alkyl in the substituents noted above can be mono to fully substituted with fluorine or mono or disubstituted with, for example, Cl, Br, I, NO2, CN, C? -C8 alkyl, O (d-C8 alkyl), N ( d-C8 alkyl) 2, S (d-C8 alkyl), or SO2 (d-C8
Alkyl), CO2 (C? -C8 alkyl), CONH (d-C8 alkyl), CON (C? -C8 alkyl) 2, or Si (d-C8 alkyl) 3. Each portion of phenyl, phenoxy, thiophenoxy, pyridinyloxy and pyridinylthio in the substituents noted above can be mono- or tri-substituted with, for example, F, Cl, Br, I, NO, CN, C? -C8 alkyl, O (C? C8 alkyl), N (C? -C8 alkyl) 2, S (d-C8 alkyl), or SO2 (C? -C8 alkyl),
CO2 (C? -C8 alkyl), CONH (d-C8 alkyl), CON (C? -C8 alkyl) 2, and Si (C? -C alkyl) 3. Preferred substituents include F, Cl, Br, I, NO2, CN, O (C3-C alkenyl), or O (C3-C4 alkynyl); d-C alkyl, O (C1-C4 alkyl), N (C? -C alkyl) 2, S (C? -C4 alkyl), SO2 (d-C4 alkyl), CO2 (d-C alkyl),
CONH (C? -C alkyl), or CON (d-C alkyl) 2 (each alkyl optionally mono to completely substituted with fluorine); or phenyl or phenoxy (each
# optionally possessing 1 to 3 substituents selected from the group consisting of F, Cl, Br, CN, CF3, N02, and CH3). Phenyl, pyridinyl and 1-alkylpyrazolyl portions possessing one to three such substituents 5 are frequently preferred. One embodiment of the invention which is frequently of special interest are compounds of Formula I wherein AR 'represents a substituted phenyl portion of the formula:
where A represents F, Cl, Br, NO, CN, d-C4 fluoroalkyl, CO2 (d-C)
Alkyl), CONH (C? -C4 alkyl), CON (d-C4 alkyl) 2, SO2 (d-C4 alkyl), or
SO2 (C? -C4 fluoroalkyl); B represents C? -C alkyl, F, Cl, Br, O (C? -C alkyl), O (C? -C4 fluoroalkyl), S (C1-C alkyl), S (C1-C4 fluoroalkyl),
N (C? -C4 alkyl) 2; or phenyl, phenoxy or phenylthio each optionally possessing 1 to 3 substituents selected from the group consisting of
F, Cl, Br, CN, CF3, NO2, and CH3; and D and J each independently represents H or CH3 with the proviso that at least one of D and J represents H. Compounds of this type wherein A represents F, Cl, Br,
CF3, NO2, or CO2CH3; B represents F, Cl, Br, CH 3, OCH 3; D represents H or
CH3; and J represents H are frequently preferred. Such compounds
Wherein Ar 'represents 2,6-dichlorophenyl, 2,6-difluorophenium, 2-chloro-6-fluorophenyl, 2-methoxycarbonyl-6-methylphenyl, 2-chloro-6-methoxycarbonylfenyl,
^ ~ 2-f luoro-6-methoxycarbonylfenyl, 2-methoxy-6- (trifluoromethyl) phenol, 2,6-dichloro-3-methylphenyl and 2,6-difluoro-3-methylphenyl are often especially preferred . Another embodiment of the invention which is often of special interest are compounds of Formula I wherein AR 'represents a substituted 3-pyridinyl moiety of the formula:
wherein L and M each independently represents H, d-C4 alkyl,
C? -C fluoroalkyl, O (C? -C4 alkyl), O (C? -C4 fluoroalkyl), O (C2-C4 alkoxyalkyl), O (C3-C4 alkenyl), O (C3-C4 alkynyl), S (C1-C4 alkyl),
S (C? -C4 fluoroalkyl), SO2 (C? -C4 alkyl), SO2 (d-C4 fluoroalkyl), F, Cl,
Br, I, CN, NO2, C6H5, CO2 (d-C4 alkyl), CO2 (C3-C4 alkenyl), CO2 (C3-C4 alkynyl), CON (C1-C alkyl) 2, or CONH (C? -C4 alkyl), with the condition of
that no more than one of L and M represents H; and T represents H, F, Cl, Br, I,
CH3, or CF3. Such compounds wherein AR 'represents a 2- (chloro, bromo or tpfluoromethyl) -4- (C? -C2 alkyl) -3-pyridinyl, or 4-methoxycarbonyl-3-pyridinyl are frequently more preferred. Specifically preferred AR 'portions of this type include 2-fluoro-4-methyl-3-pyridinyl, 2-chloro-4-methoxy-3-pyridinyl, 2-chloro-4-ethoxy-3-pyridinyl, 2-chloro- ^ 4- (1-methylethoxy) -3-pyridinyl, 2-chloro-4-propoxy-3-pyridinyl and 4-methoxycarbonyl-3-pyridinyl. A third embodiment of the invention which is often of special interest are compounds of Formula I wherein AR 'represents
A portion of 3-, 4-, or 4-pyrazolyl substituted with a d-C3 alkyl group in the 1-position, with at least one Cl, Br, I or CF3, and, optionally, with an OCH3 or CH3 group . Compounds of this type wherein AR 'represents a portion of 1-methyl-4-halo-3-pyrazolyl, 1-methyl-4-halo-5-pyrazolyl or 1-tf-ethyl-3- (trifluoromethyl) - 5- (methyl, methoxy or halo) -4-pyrazolyl are sometimes
most preferred. The term "alkyl" as used herein includes linear, branched and cyclic alkyl portions. Examples include methyl, ethyl, 1-methylethyl, butyl, 2-methylpropyl, 1,1-dimethyl-ethyl, cyclopropyl, and cyclopropylmethyl. The term fluoroalkyl includes alkyl portions
replaced with up to the maximum possible number of fluorine atoms. Examples include trifluoromethyl, 2-fluoroethyl, and 1,1, 2,2-tetrafluoroethyl. The term "halo" includes fluoro, chloro, bromo and iodo. Some specifically preferred compounds of Formula I include S, S-dimethyl-N- (2,5-dichlorophenyl) sulphimimine, S, S-dimethyl-N- (2,6-20 dichloro-3-methylphenyl) sulphimimine, S, S -dimethyl-N- (2,6-difluorofenyl) sulphimimine, S, S-dimethyl-N- (2,6-difluoro-3-methylphenyl) sulfimlimin, S, S-dimethyl-N- (2 -chloro-6-fluorophenyl) sulphimimine, S, S-dimethyl-N- (2-methoxycarbonyl-6-chlorophenyl) sulphimimine, S, S-dimethyl-N- (2-methoxycarbonyl-6-fluorophenyl) sulphonimine, S, S -dimethyl-N- (2-methoxycarbonyl-6-methylphenyl) sulphimimine, S, S-dimethyl-N- (2-methoxy-6-trifluoromethyl) phenyl) sulfyrimine, S, S-dimethyl-N- (2-fluoro-4-methyl-3-pyridinyl) sulphimimine, S, S-dimethyl-N- (2-chloro-4-methoxy-3-pyridinyl) sulphimimine, S, S-dimethyl-N- (1 -ethyl-5-methyl-3- (trifluoromethyl) -4-pyrazolyl) sulfyrimine, S, S-dimethyl-N- (1-methyl-4-bromo-3-pyrazolyl) sulphimimine, and S, S-dimethyl -N- (1-methyl-5, 4-bromo-5-pyrazolyl) sulfilimine. The N-arylsulfilimine compounds of Formula I can be prepared by various general methods known in the art. The methods described in Chemical Reviews. 77. 409-435 (1977),
• Svnthesis, 165-185 (1981), and Russian Chemical Reviews. 59. 819-831 10 (1990) and references cited herein may be used with only routine adaptation. It is often preferred to use the method of preparation which involves the reaction of a sulfoxide compound of the formula:
R / O = S \ R '
wherein R and R 'are as defined for the compounds of Formula I
with an arylamine compound of Formula Il la: AR'-NH2 wherein AR 'is as defined for the compounds of Formula I and an activator such as sulfur trioxide, 2-sulfobenzoic acid cyclic anhydride, trifluoroacetic anhydride, chloride of carbonyl or chloride
oxalyl. The reaction mixture is treated with a base, such as an alkali metal hydroxide, to complete the process. The process is generally carried out at temperatures between about -70 ° C and about 20 ° C in an organic solvent, such as dichloromethane. Typically, a mixture of the activator and the solvent is prepared and cooled to the desired reaction temperature and the sulfoxide compound is then added. After a short reaction period, the arylamine compound is added and allowed to react for one to four hours. Finally, an aqueous solution of an alkali metal hydroxide is added and the phases are separated. The product of
The compound of N-arylsulfilimine can be recovered by evaporative removal of the volatile organic components from the reaction mixture and can be purified by conventional means, such as by recrystallization. However, it is not necessary to recover the compound; the N-arylsulfilimine compound can be used as a catalyst in
the form of the solution in an organic solvent obtained in the separation of the phases. Alternatively, the N-arylsulfilimine compounds of Formula I can be prepared by reacting a sulfide compound of the formula R-S-R 'with an arylamine compound of Formula
I l and chloride. The process is generally carried out at temperatures between about -20 ° C and about 20 ° C in an organic solvent, such as dichloromethane. Typically, a solution of the sulfide compound in the solvent is prepared and cooled to the desired reaction temperature. Approximately one molar equivalent of chlorine is added and
Then approximately one molar equivalent of each of the arylamine compound and an aromatic tertiary amine base, such as
# pyridine, a picoline, a collidine, a (mono or poly) halopyridine, nicotinamide, ethyl nicotinate, quinoline and the like are added. Alternatively, an aqueous base, such as a solution of a hydroxide
Alkali metal or carbonate can be used as the base. After a short reaction period, a solution of an N-arylsulfilimine compound as a solution in an organic solvent is formed. The N-arylsulfilimine compound can be recovered by means of
, f conventional or can be used in the form of the solution in a
obtained organic solvent. The aromatic tertiary amine hydrochloride by-product sub-product obtained when an aromatic tertiary amine base is used can be removed from the mixture by extraction with water before use, if desired. The N-arylsulfilimine compounds of Formula I are useful as catalysts in the preparation of N-arylarylsulfonamide compounds of Formula IV: Q- SO2NH-AR
by the reaction of aromatic sulfonyl chloride compounds of Formula I I: Q- SO2Cl
with arylamine compounds of Formula I II:
AR- NH2 wherein Q and AR each independently represents a portion of aromatic hydrocarbyl or aromatic heterocyclyl. A N-arylsulphimyl compound of Formula I wherein the AR 5 portion is identical with the AR portion of the arylamine compound of Formula I I I is very frequently used and is highly preferable. The use of an N-arylsulphimymine catalyst wherein AR 'is different from the AR portion of the arylamine compound generally produces an N- compound.
* arylarylsulfonamide of Formula IV, wherein AR is the AR 'of the catalyst
N-arylsulphyrimine in addition to the desired compound of Formula IV wherein AR is the AR portion of the arylamine compound. This generally reduces the performance based on the sulfonyl chloride compound and can create a significant separation problem. It is essential that the AR 'of the N-arylsulfilimine compound is identical to the AR of the
A compound of arylamine when the N-arylarylsulfonamide compound prepared is an agricultural chemical or a pharmaceutical chemist, since the commercial utility of such chemicals would be compromised by the presence of the related compounds that are formed when the AR 'portion is not identical to the AR portion. The portions AR of the compounds of Formula III which are employed in the process of the invention are the same as those described and characterized herein by the portions AR 'of the N-arylsulphimine catalysts of Formula I. The preferences by categories of AR, by substituents, and by substituent patterns
specific ones are the same as those described for AR '.
The Q portion of the compounds of Formula I I represents a portion of aromatic hydrocarbyl or aromatic heterocyclyl. This definition is inclusive of all portions of aromatic hydrocarbyl and aromatic heterocyclyl whether or not these portions possess
substituents Examples of suitable aromatic hydrocarbyl moieties include phenyl, naphthyl, phenanthrenyl and indenyl. Examples of suitable aromatic heterocyclic portions include pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3-triazinyl, quiolinyl, quinazolinyl, quinoxalinyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl,
pyrazolyl, 1,4-oxadiazolyl, 1,4-oxadiazolyl, 1,4-thiadiazolyl, 1,4-thiadiazolyl, 1,4-triazolyl, benzofuranyl, benzo [b] thienyl. , indolyl, [1, 2,4] triazolo [1, 5-a] pyrimidinyl, [1, 2,4] triazolo [1, 5-c] -pyrimidinyl, [1, 2,4] triazolo [1, 5 -a] pyridinyl, pyrazolo- [1, 5-a] pi rim idin ilo, and [1, 2,4] triazolo [1, 5-a] [1, 3,5] -triazinyl. The chloride compounds of
Sulfonyl wherein Q represents substituted phenyl are very frequently employed and processes involving such compounds, especially
E ^ * ~ such compounds having one or two ortho substituents are frequently preferred accordingly. The compounds wherein Q represents a substituted pyridinyl moiety, especially such
compounds that possess at least one ortho substituent are also sometimes preferred. The sulfonyl chloride compounds wherein Q represents 5-amino-1, 2,4-triazin-3-yl or [1, 2,4] triazolo- [1, 5-a] pyridin-2-yl moiety are often of special interest. Substituents possessed by hydrocarbyl portions
aromatic and heterocyclyl Q include any substituent that is stable in the presence of the other substituents in the
'f' aryl sulfonyl and which does not react with the arylamine compound or the sulfilimine catalyst. Suitable substituents include F, Cl, Br, I, N02, CN, d-C8 alkyl, O (d-C8 alkyl), O (C3-C8 alkenyl), O (C3-C8 alkenyl), N (d-) C8 alkyl) 2, S (d-C8 alkyl), S (C3-C8 alkenyl), S (C3-C8 alkenyl), SO2 (C1-C8 alkyl), SO2 (C3-C8 alkenyl), SO2 (C3-C8 alkenyl), C02 (d-C8 alkyl), CO2 (C3-C8 alkenyl), CO2 (C3-C8 alkenyl), CONH (d- C8 alkyl), CON (C? -8 alkyl) 2, Si (C? C8 alkyl) 3, phenyl, phenoxy, thiophenoxy, pyridinyloxy, and pyridinylthio. Each alkyl in the substituents noted above
can be mono to fully substituted with fluorine or mono or disubstituted with, for example, Cl, Br, I, NO, CN, C? -C8 alkyl, O (C? -C8 alkyl), N (C? -C? Alkyl) ) 2, S (d-C8 alkyl), or SO2 (d-C8 alkyl), CO2 (d- C8 alkyl), CONH (d-C8 alkyl), CON (d-C8 alkyl) 2, or Si (d- C8 alkyl) 3. Each portion of phenyl, phenoxy, thiophenoxy, pyridinyloxy and pyridinylthio in the
Substituents noted above may be mono- or trisubstituted with, for example, F, Cl, Br, I, NO2, CN, d-C8 alkyl, O (d-C8 alkyl), N (C? -8
^^ alkyl) 2, S (C? -C8 alkyl), or SO2 (C? -C8 alkyl), CO2 (d-C8 alkyl), CONH (C? -C8 alkyl), CON (d-C8 alkyl) 2 , and Si (C? -C8 alkyl) 3. Preferred substituents include F, Cl, Br, I, NO, CN, O (C3-C20 alkenyl), or O (C3-C alkynyl); C1-C4 alkyl, O (C? -C4 alkyl), N (C? -C4 alkyl) 2, S (d-C4 alkyl), SO2 (C1-C4 alkyl), CO2 (C? -C4 alkyl), CONH (C? -C4 alkyl), or CON (C? -C4 alkyl) 2 (each alkyl optionally mono to completely substituted with fluorine); or phenyl or phenoxy (each optionally possessing 1 to 3 substituents selected from the group
consisting of F, Cl, Br, CN, CF3, NO2, and CH3).
Compounds of fluoride or sulfonyl bromide compounds
- Jfc corresponding to the sulfonyl chloride compounds of Formula II could be employed in the process of the invention in place of the compounds of Formula I I. The compounds of fluoride and sulfonyl bromide, however, are not commercially available. generally available, especially at a cost comparable to the cost of the compounds of Formula II, and are not commonly used. Some specifically preferred sulfonyl chloride compounds of formula II for use in the process of the invention include
2-chlorosulfonyl-5-ethoxy-7-fluoro [1, 2-4] -triazolo [1, 5-c] pyrimidine, 2-chlorosuifonyl-5-methoxy-8-fluoro [1, 2,4] triazolo [ 1, 5-c] pip "midin, 2-chloro-3,5-l-methoxy-7-methyl [1, 2,4] triazolo [1, 5-c] pyrimidine, 2-chlorosulfonyl-5-ethoxy-7 methyl [1, 2,4] triazolo [1, 5-a] pyrimidine, 2-chlorosulfonyl-5,7-dimethoxy [1, 2,4] triazolo [1, 5-a] -pyrimidine, 2-chlorosulfonyl-5 , 7- 15 dimethyl [1, 2,4] triazolo- [1, 5-a] pyrimidine, 2-chlorosulfonyl-5-methoxy-7-methyl [1, 2,4] -triazolo [1, 5] a] pyridine, and 2-chlorosulfonyl-5-methoxy-8-chloro [1, 2,4] triazolo [1, 5-a] pyridine The process is carried out by contacting a sulfonyl chloride compound of Formula II with an arylamine compound of Formula II I in
the presence of an aromatic tertiary amine compound and a catalytic amount added of an N-arylsulphimyne compound of Formula I: R / AR'- = S \ R 'where AR', R, and R 'are as defined above, preferably in
< * where AR is selected to be identical to AR in the arylamine compound. Any of the known methods for contacting the reagents and catalyst can be used. For example, the sulfonyl chloride compound of Formula II can be mixed with an organic solvent and then an arylamine compound of Formula II I, one molar equivalent or more of an aromatic tertiary amine , such as pyridine, a picoline , a collidine, a (mono or poly) halopyridine,
# nicotinamide, quinoline and the like, and a catalytically effective amount
of a N-arylsulphimine compound of Formula I are added. The amount of the arylamine compound of Formula I I I employed - including the arylamine compound contained in the N-arylsulphimimine catalyst - is at least about one molar equivalent. Quantities in excess of a molar equivalent are not detrimental to the process, but
are generally not necessary. The reagents can be combined in any order. Frequently it is preferable to prepare the N-arylsulphimine catalyst of Formula I in a vessel and to add the arylamine compound of Formula II I, the sulfonyl chloride compound of Formula II, and the aromatic tertiary amine thereto. When AR of reagent
arylamine and AR 'of the sulfilimine catalyst are selected to be identical, the arylamine reagent of Formula III may be present during the preparation of the N-arylsulphimymine catalyst; that is, an excess of arylamine can be used in the preparation of the N-arylsulphimymine catalyst and the excess employed as all or a portion of the arylamine reagent in the process. The product of N-arylarylsulfonamide
* desired of Formula IV is prepared in the resulting reaction. A catalytically effective amount of the N-arylsulphyl compounds of Formula I can be easily determined for each preparation of N-arylarylsulfonamide by routine experimentation. In most cases, an amount between 2 and 30 percent mole of the amount of sulfonyl chloride compound of Formula II is employed. The process is generally carried out at a temperature between -
# 20 ° C and 50 ° C. The lower limit is because the reaction becomes
too slow to be practical at very low temperatures and the higher limit is because the N-arylsulfilimine catalysts become unstable at elevated temperatures. Temperatures between 0 ° C and 30 ° C are frequently preferred. The pressure in the reactor is not believed to be critical; pressures near atmospheric are generally
preferred. Continuous and effective mixing is usually useful. A reaction period of 30 minutes to 16 hours is typical for the process to be completed. The reaction is generally carried out under essentially anhydrous conditions. Solvents that are suitable for such processes are solvents
Organic compounds in which the aromatic sulfonyl chloride compound of formula II, the N-arylsulphimine compound of Formula I, and the arylamine compound of Formula I I I have some solubility and which are inert with respect to the reagents employed. Suitable solvents include acetonitrile, butyronitrile, benzonitrile, dichloromethane, 1,2,2-dichloroethane, tetrahydrofuran, 1,2-dimethoxyethane, toluene, chlorobenzene, and the like. Sufficient organic solvent is used to facilitate the agitation of the reaction mixture and, thereby, achieve homogeneity and promote good contact between the reagents. The aromatic tertiary amine base used is a factor to determine the results obtained. Pyridine or a picoline (2-, 3-, or 4-picoline, or a mixture) are frequently preferred because they are the least expensive. Quinoline and nicotynamide are also sometimes preferred because, in some cases, higher yields are effected. The base that is optimal in any specific situation depends on the nature of other reagents employed, including the N-arylsulphimymine catalyst, and the nature (particularly the pKa) of the N-arylarylsulfonamide product being prepared. The by-product formation of N-arylbisarylsulfonimide can be minimized and the yield of the desired N-arylarylsulfonamide can be maximized by the
selection of the most appropriate tertiary amine base. The optimum aromatic tertiary amine base for any combination of aryl sulfonyl chloride compound and arylamine compound can be determined by routine experimentation. The N-arylarylsulfonamide products of Formula IV can be
recovered from the process medium by standard procedures, including by filtration to collect insoluble solids and by extracting the final reaction mixture with water and removing the solvent and any other volatile material by evaporation, preferably under reduced pressure. The products obtained in the recovery can be + • purified generally by standard procedures, such as recrystallization. The aromatic sulfonyl chloride compounds of Formula I I and the arylamine compounds of Formula I I I are known in the art or can be prepared by routine adaptation of the methods described in the art. The following examples are provided to illustrate the invention. They should not be interpreted as limiting the claims. 10 EJ EMPLOS
1 . Preparation of N- (2,6-difluorophenyl) -S.S-dimethyl-sulfilimine A paste of 2.39 g (grams) (13.0 mmol (millimoles)) of anhydride
Cyclic 2-sulfobenzoic acid in 20 ml (milliliters) of dichloromethane was prepared and cooled to 3 ° C. To this was added 0.85 ml (0.94 g., 12 mmol) of dimethyl sulfoxide (DMSO) in the form of drops over a period of 1 min with stirring and cooling. The temperature was raised to 5 ° C and the mixture became homogeneous. After 5 min, 1.41 g (11 mmol) of 2,6-difluoroaniline was added with stirring and cooling over a period of 2 min. A white precipitate formed and the temperature rose to 9 ° C. After 2 hours, the precipitate, which amounted to 3.2 g, was collected by filtration and made into 15 ml of fresh dichloromethane. Ten ml of 2N aqueous sodium hydroxide was added and the mixture was stirred. The
Two light liquid phases which formed were separated and the organic phase was dried over magnesium sulfate and concentrated by evaporation under reduced pressure to obtain a clear oil. This oil was dissolved in 5 ml of ether and 5 ml of cyclohexane was added. The mixture was cooled to 5 ° C and the white needles that formed were collected by filtration and dried to obtain 0.88 g of the title compound. 1 H NMR [300 MHz] (CD3CN) ppm: 6.80-6.75 (m, 2H), 6.64-6.5 (m, 1 H), 2.70 (s, 6H); Mass Spectrum (m / z): 189 (M +, 75), 174 (M + -CH 3, 100), 159 (M + -C 2 H 6, 90).
2. Preparation of N- (2,6-dichlorophenyl) -S, S-dimethyl-sulphylamine A paste of 23.9 g (130 mmol) of 2-sulfobenzoic acid cyclic anhydride in 205 ml of dichloromethane was prepared and cooled to 4 ° C. To this was added 9.46 g (120 mmol) of dimethyl sulfoxide in three portions over a period of 3 to 4 min with stirring and cooling, rinsing the vessel with about 10 ml of dichloromethane to insure complete transfer. The temperature rose to between 5 and 6 ° C. After 10 min, 17.9 g (1 10 mmol) of 2,6-dichloroaniline was added with stirring and cooling over a period of 4 min. A white precipitate formed. After 90 min, the mixture was a thick paste and the temperature was 15 ° C. The mixture was treated with 207 g of 1 N and then 5 ml of 50 percent aqueous sodium hydroxide. The two clear liquid phases that formed were separated and the aqueous phase was extracted with 150 ml of dichloromethane. The organic phase and extract were combined and washed with 100 ml of water, dried over magnesium sulfate, filtered and concentrated by evaporation under reduced pressure to obtain a light golden oil. This oil was crystallized from diethyl ether to obtain the title compound in two batches weighing 1.94 and 2.03 g (16 percent theory) as a white solid. 5 1 H N MR [300 MHz] (CD3CI) ppm: 7.21 -7.18 (d, 2H), 6.68-6.63 (dd, 1 H), 2.68 (s, 6H); Mass Spectrum (m / z): 221 (M +, 50), 206 (M + -CH 3, 100), 191 (M + -C 2 H 6, 45).
3. Preparation of N- (2-chloro-6-methoxycarbonylphenyl) -S, S-10 dimethylsulphimimine Method A) A solution of 5.0 ml (0.068 mol) of dimethyl sulfide in 80 ml of dichloromethane was prepared in a round bottom flask and it was cooled to -10 ° C. Chlorine gas (4.6 g, 0.065 mol) was added to the vapor space of the flask through a spray tube with cooling and stirring
and, after about 2 min, 12 g (0.065 mol) of methyl 3-chloroanthranilate was added (2-chloro-6-methoxycarbonyl-phenylamine) with stirring and cooling. After about 2 min, 10.2 g (0.13 mol) of pyridine was added slowly with stirring and cooling and the mixture was allowed to react at -10 ° C for 10 min. The
The mixture was analyzed by HPLC (high pressure liquid chromatography) (5 mm pack of Shandon Hypersil Phenyl, 60:40:01 levigant acetonitrile: water: phosphoric acid, and UV detector set at 237 nm (nanometer)) and it was found to be 20 percent methyl 3-chloroanthronilate and 80 percent of the title compound (normalized on these
two substances). The volatile components of the mixture were removed by evaporation under reduced pressure to obtain the title compound in crude form as a white solid. 1H NMR [300 MHz] (CD3CI) ppm: 7.82 (dd, 1H, J = 1.3, 8.1), 7.69 (dd, 1H, J = 1.3, 8.1), 7.33 (t, 1H, J = 8.1), 3.89 (s, 3H9, 3.37 (s, 6H); Ultraviolet spectrum: maximum at 213 and 298 nm; Mass Spectrum (m / z): 246 (M +, 60), 184 (M + -SC2H6, 100), 154 (M + -OSC3H8, 65) The following compounds were prepared in a similar manner: N- (2-chlorophenyl) -S, S-dimethylsulphimycin; 1H NMR [300 MHz] (CD3CN) ppm: 7.52 (dd, 1H, J = 7.7, 1.7), 7.49 (dd, 1H, J = 7.7, 1.8), 7.35 (dt, 1H, J = 7.6, 1.7), 7.29 (dt, 1H, J = 7.6, 1.7), 2.56 (s, 6H); Ultraviolet spectrum: maximum at 210 and 260 nm;
N- (2-methoxy-6- (trifluoromethyl) phenyl) -S, S-dimethyl-sulphylamine; 1H NMR [300 MHz] (CD3CN) ppm: 7.43 (t, 1H, J = 8.0), 7.30 (d, 1H, J = 8.0), 7.24 (d, 1H, J = 8.0), 3.93 (s, 3H) 3.29 (s, 6H);
2,6-dichloro-3-methylphenyl) -S, S-dimethyl-sulphonimine; • NMR [300 MHz] (CD3CN) ppm: 7.10 (d, 1H, J = 8.2), 6.61 (d, 1H, J = 8.2), 2.84 (s, 6H), 2.27 (s, 3H); Mass Spectrum (m / z): 236 (MH +), 208, 195, 174, 147;
N- (2-methoxycarbonylphenyl) -S, S-dimethylsuflimine; • NMR [300 MHz] (CD3CN) ppm: 7.92 (dd, 1H, J = 8.0, 1.5), 7.48 (dt, 1H, J = 7.8, 1.4), 7.14 (d, 1H, J = 8.1), 7.06 ( dt, 1H, J = 8.1, 1.0), 3.85 (s, 3H), 2.56 (s, 6H);
N- (2-methyl-6-nitrophenyl) -S, S-dimethylsu! Fimiline; 1 H NMR [300 MHz] (CD 3 CN) ppm: 7.82 (d, 1 H, J = 8.2), 7.58 (d, 1 H, J = 7.4), 7.34 (brdd, 1 H, J = 7.8, 7.3), 3.38 (s, 6H), 2.48 (s, 3H); 13C NMR [75.5MHz) (CD3CN) ppm: 146.0, 138.5, 137.4, 132.6, 128.2, 124.6, 33.9, 19.3;
N- (2-chloro-4- (1-methylethoxy) -3-pyridinyl) -S, S-dimethyl-sulphorylimine; H NMR [300 MHz] (CD3CN) ppm: 8.08 (d, 1 H, J = 5.8), 7.03 (d, 1 H, J = 5.8), 4.8 (septet, 1 H, J = 6.1), 3.26 (s) , 6H), 1 .37 (d, J = 6.0, 6H);
N- (5-bromo-2-pyridinyl) -S, S-dimethylsulphimimine; • N MR [300 MHz] (CD3CN) ppm: 8.21 (d, 1 H, J = 2.3), 7.74 (dd, 1 H, J = 8.8,
2. 4), 6.98 (d, 1 H, J = 8.8), 3.36 (s, 6H).
Method B) A mixture of 7.3 g (94 mmol) of dimethyl sulfoxide and 100 ml of dichloromethane was prepared and cooled to -60 ° C and then 19.8 g (94 mmol) of trifluoroacetic anhydride was added slowly with stirring. A white solid formed in about 5 min at which time a solution of 24 g (130 mmol) of methyl 6-chloroanthranilate in 15 ml of dichloromethane was added slowly with stirring. The mixture was allowed to react and warm to about 0 ° C with stirring. The white solid that formed first was redissolved. The mixture was then neutralized with 70 ml of 10 percent by weight potassium hydroxide in water with stirring for 30 min. The mixture turned brown. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane. The organic phase and the extracts were combined and concentrated by evaporation under reduced pressure. The brown tarry residue was triturated with diethyl ether to induce solidification, recovered by filtration and washed with diethyl ether to obtain the title compound in crude form as a greenish-brown solid. It was found by HPLC that the solid consists of about 80 percent of the title compound and about 20 percent of methyl 6-chloroanthranilate.
Method C) A solution of 3.2 g (0.039 mol) of sulfur trioxide in 6 ml of dichloromethane was cooled to 0 ° C and 1.4 g (0.018 mol) of dimethyl sulfoxide was added slowly with stirring and cooling. After 10 min, 3.3 g (0.018 mol) of methyl 6-chloroanthranilate was added as a solid with stirring and cooling. The mixture was allowed
will react for 15 min and then 2.8 g (0.035 mol) of pyridine is added. It was determined by HPLC that the resulting solution contained the title compound and unreacted methyl 6-chloroanthranilate in a ratio of 61:39.
4. Preparation of N- (2-chloro-6-methoxycarbonylphenyl) -S, S-tetramethylene-sulphonimine A solution of 3.0 ml (34 mmol) of tetrahydrothiophene and 50 ml of dichloromethane was cooled to -10 ° C and then 2.3 g ( 32 mmol) of chlorine was sprayed with cooling and stirring. An amount of 6.3 g (34 mmol) of methyl 6-25-chloroanthranilate and then 5.4 g (68 mmol) of pyridine were added. It was found that the ratio of the title compound to unreacted methyl 6-chloroanthranilate in the product mixture was 65:35 by HPLC. 1 H NMR [300 MHz] (CD3CN) ppm: 7.78 (d, 1 H, J = 8.0), 7.44 (d, 1 H, J = 8.0), 5 6.64 (t, 1 H, J = 8.0 =, 3.63 (s, 3H), 3.24 (m, 4H), 2.37 (m, 2H), 2.16 (m, 2H), Ultraviolet spectrum: maximum at 220 nm, Mass Spectrum (m / z): 272 (MH +, 100 ), 240 (M + -OCH4, 15), 184 (M + -SC4H8, 100), 87 (SC4H7 +, 40).
. Preparation of N- (2-chloro-6-methoxycarbonylphenyl) -S-methyls-10-phenylsulphimimine A solution of 3.0 g (24 mmol) of methyl phenyl sulfide in 30 ml of dichloromethane was cooled to -10 ° C and 1 .7 g (24 mmol) of chlorine was sprayed with cooling and stirring. To this were added with cooling and stirring 4.5 g (24 mmol) of solid methyl 6-chloroanthranilate and then
3.8 g (48 mmol) of pyridine. The product mixture contained the title compound and methyl 6-chloroanthranilate in a ratio of 60:40 as determined by HPLC. Ultraviolet spectrum: maximum at 215 and 300 nm; Mass Spectrum (m / z): 308 (MH +, 40), 276 (M + -OCH4, 35), 261 (M + -OC2H7, 10), 184 (M + -SC7H8,
35), 124 (SC7H8 +, 40).
6. Preparation of N- (2,4,6-trichlorophenyl) -S, Sd-methyl-sulphylamine A solution of 1.1 ml (15 mmol) of dimethyl sulfide in 170 ml of dichloromethane was cooled to -10 ° C and 0.90 g ( 13 mmol) of chlorine
additions through a spray tube with cooling and stirring.
Subsequently 23.3 g (120 mmol) of 2,4,6-trichloroaniine and then
# 22 g (170 mmol) of quinoline were added with cooling and stirring. The resulting product was a mixture of the title compound and unreacted 2,4,6-trichloroaniline. 7. Preparation of N- (4-bromo-1-methyl-5-pyrazolyl) -S, S-dimethylsulphimimine A solution of 0.60 ml (8.2 mmol) of dimethyl sulfide in 30 ml of dichloromethane was cooled to -20 °. C and 0.50 g (7.0 mmol) of chlorine are
"^ r added through a spray tube with cooling and stirring.
Subsequently, 1.0 g (5.7 mmol) of 5-amino-4-bromo-1-methylpyrazole and then 1.0 g (12.7 mmol) of pyridine were added with cooling and stirring. A 2 ml aliquot of this mixture was removed and the light yellow solids present were collected by filtration and washed with deuteroacetonitrile. 15 1 H NMR [300 MHz] (CD3CN / D2O) ppm: 7.58 (s, 1 H), 3.77 (s, 3H), 3.17 (s, 6H).
8. Preparation of N- (2,6-dif-luo-phenyl) -8-f-luoro-5-methoxy-2,41-triazolori-5-clpyrimidine-2-sulfonamide using catalyst
Sulfilimine A mixture consisting of 1.4 g (11 mmol) of 2,6-difluoroaniline, 0.86 g (11 mmol) of pyridine, and 30 ml of dry acetonitrile was prepared and cooled to 1 -3 ° C. N- (2,6-difluorophenyl) -S, S-dimethylsulphimimine (0.15 g, 0.78 mmol) was added and then 2.7 g (10 mmol) of 2-chlorosulfonyl-8-fluoro-5-methoxy [1, 2, 4-] triazole [1,5-c] pyrimidine in 10 ml of dry acetonitrile was added dropwise over a period of 30 s with stirring and cooling to the yellow solution. An exotherm raising the temperature to 10 ° C was observed and a white precipitate formed gradually. After 80 min, the mixture was analyzed quantitatively by HPLC using standards and it was found that 70 percent of the chlorosulfonyl compound was converted to the title compound, 24 percent was converted to N, N-bis ((8-fluoro-5- methoxy [1, 2,4] triazolo [1, 5-c] pyrimidin-2-yl) sulfonyl) -2,6-difluorophenylamine and 4 parts were converted to 8-fluoro-5-methyloxy [1, 2.4 ] triazolo [1, 5-c] -pyrimidine-2-sulfonic acid. 9. Preparation of N- (2,6-dichlorophenyl) -7-fluoro-5-ethoxy-1, 2,4-triazolo [1,5-clpyrimidine-2-sulfonamide using sulfilimine catalyst. A mixture consisting of 7.33 g (42.5 mmol) of 2,6-dichloroaniline,
14.13 g 847.4 mmol) of 94.2 percent purity 2-chlorosulfonyl-7-fluoro-5-ethoxy [1, 2,4] triazolo- [1, 5-c] pyrimidine, 6.72 g (55.0 mmol) of nicotinamide, and 81 .4 g of dry acetonitrile was prepared and cooled to 4 ° C. N- (2,6-dichlorophenyl) -SS-dimethylsulphimimine (1.15 g, 5.15 mmol) was then added with stirring and cooling. Cooling and stirring were maintained
for 3 hours and then the mixture was allowed to warm to room temperature. After 6 hours, the mixture was analyzed quantitatively by HPLC using standards and the yield of the title compound was found to be 87 percent of the theory. A yield of 3 percent of 7-fluoro-5-ethoxy [1, 2,4] -triazolo [1,5- 25 c] pyrimidine-2-sulfonic acid was also found.
. Preparation of N- (2-chloro-6-methoxycarbonyl-phenyl) -7-fluoro-5-ethoxy-1, 2,4-triazole-1, 5-clpyrimidine-2-sulfonamide using sulphimimine catalyst without recovering a solution of 0.7 ml (96 mmol) of Dimethyl sulphide in 20 ml of dichloromethane was prepared in a round bottom flask and cooled to -10 ° C. Chlorine gas (0.60 g, 85 mmol) was added to the vapor space of the flask through a spray tube with cooling and stirring and, after about 2 min, 18 g (97 mmol) of 3-chloroanthranilate
Methyl (2-chloro-6-methoxycarbonylphenylamine) was added with stirring and cooling. After about 2 min, 9.8 g (124 mmol) of pyridine was added slowly with stirring and cooling and the mixture was allowed to react at -10 ° C for 10 min. A solution of 21 g (75 mmol) of 2-chlorosulfonyl-7-fluoro-5-ethoxy [1, 2,4] triazolo- [1, 5-c] pyrimidine
In 90 ml of dichloromethane was prepared, cooled to 0 ° C and then added with cooling and stirring. The reaction was essentially completed by HPLC analysis in 5-6 hours. After settling overnight, about 50 ml of dichloromethane was removed by distillation and 50 ml of 2-propanol was added. He
The remaining dichloromethane was removed by distillation until the upper temperature was 62-64 ° C and the kettle temperature was 72-74 ° C. The resulting 2-propanol paste was cooled to 5 ° C and, after 30 min, filtered. The collected solids were rinsed with 2x50 ml of methanol and air dried to obtain 29.8 g (85 percent theory)
of the title compound.
The same product was obtained in a similar way using the
# N- (2-chloro-6-methoxycarbonylphenyl) -S, S-tetramethylene-sulphonimine product mixture of Example 4 as the catalyst. A 9 ml portion of that product was diluted with 75 ml of dichloromethane, the solution was cooled to -10 ° C, and 9.3 g (50 mmol) of methyl 3-chloroanthranilate and then 4.8 g (60 mmol) of pyridine were added. they were added with cooling and stirring. 2-Chlorosulfonyl-7-fluoro-5-ethoxy [1, 2,4] triazolo [1, 5-c] -pyrimidine
(15.5 g of 91 pure percent, 50 mmol) was added with cooling to 0- _____ mf 2 ° C. The reaction was completed in 6 hours and a yield of 90
percent of the purity title compound of 98 percent was obtained in recovery. The same product was obtained in a similar way using the
. N- (2-chloro-6-methoxycarbonylphenyl) -S-methyl-S-phenylsulphimimine product mixture of Example 5 as the catalyst. A performance of 55
percent of a purity product of 98 percent was obtained. The following compounds were prepared in a similar manner using N- (2-chloro-6-methoxycarbonylphenyl) -S, S-dimethylsulfilimine as the catalyst:
N- (2-chloro-6-methoxycarbonylphenyl) -7,8-dichloro [1,4] triazolo [1,5-c] pyrimidine-2-sulfonamide, a white solid obtained in about 85 percent yield; 'NMR [300 MHz] (D6-DMSO) ppm: 1 1 .15 (s, 1 H), 7.70 (d, 1 H, J = 8.0), 7.68 (d, 1 H, J = 7.8), 7.47 ( dd, 1 H, J = 8.0, 7.8), 4.68 (q, 2H, J = 7.0), 3.71 (s,
3H), 1.45 (t, 3H, J = 7.0);
N- (2-chloro-6-methoxycarbonylpheni) -7-fluoro-5-methoxy- [1,2,4] triazoIo [1,5- c] pyrimidine-2-sulfonamide, a white solid obtained in about 70 percent of performance; 5 1 H NMR [300 MHz] (D 6 -DMSO) ppm: 11.1 (s, 1H), 7.70 (d, 1H, J = 7.9), 7.68 (d, 1H, J = 7.9), 7.46 (t, 1H, J = 7.9), 7.36, /.36 (s, 1H), 4.23 (s, 3H), 3.67 (s, 3H);
'Ww N- (2-chloro-6-methoxycarbonylphenyl) -8-chloro-5-ethoxy-7-fluoro [1, 2,4] triazolo [1,5- 10 c] pyrimidine-2-sulfonamide, a yellow solid clear obtained in approximately 80 percent yield; 1H NMR [300 MHz] (De-DMSO) ppm: 11.15 (s, 1H), 7.71 (d, 1H, J = 8.0), 7.70 (d, 1H, J = 7.9), 7.47 (dd, 1H, J = 8.0, 7.9), 4.68 (q, 2H, J = 7.1), 3.71 (s, 3H), 1.45 (t, 3H, J = 7.1); and 15 N- (2-chloro-6-methoxycarbonylphenyl) -7-chloro-5-ethoxy [1,2,4] triazolo [1,5- c] pyrimidin-2-suphonamide, a pale yellow solid obtained in approximately 82 percent of performance; 'H NMR [300 MHz] (D6-DMSO) ppm: 11.0 (s, 1H), 7.79 (s, 1H), 7.71 (d, 1H, 20 J = 8.0), 7.68 (d, 1H, J = 7.9) , 7.46 (dd, 1H, J = 8.0, 7.9), 4.68 (q, 2H, J = 7.1), 3.69 (s, 3H), 1.45 (t, 3H, J = 7.1).
11. Preparation of N- (2,6-dichlorophenyl) -7-fluoro-5-ethoxy-ri, 2,41-triazole-1,5-clpyrimidine-2-sulfonamide using sulphimimine catalyst without recovering A first solution containing about 76 mmol of 2-chlorosulfonyl- 7-fluoro-5-ethoxy [1, 2,4] triazolo [1, 5-c] pyrimidine in about 1 10 g of dichloromethane was prepared by combining 21.8 g of 75 percent purity (approximately 38 mmol) of bis (5-ethoxy-7-fluoro [1, 2,4] triazolo [1, 5-c] pyrimidin-2-yl) disulfide, 16.0 g of water and 190 g of dichloromethane, cooling the mixture to 5 ° C and adding 15.1 g (240 mmol) of chlorine gas with stirring and cooling over a period of 75 min. Another 73.0 g of water were added and the phases separated. The aqueous phase was extracted with 22.0 g of dichloromethane. The two fresh dichloromethane solutions were combined and a total of 18.3 g of water and the dichloromethane was removed by azeotropic distillation using a Dean-Stark trap. Another 105.8 g of dichloromethane were added and another 101.5 g of solvents removed by azeotropic distillation. Another approximately 10 g of dichloromethane was used to facilitate transfer to a holding vessel. A second solution of 1.35 g (22 mmol) of dimethyl sulfide in 68.2 g of dichloromethane was prepared in a round bottom flask and cooled to about 7 ° C. The gaseous chlorine (1.5 g, 21 mmol) was added to the vapor space of the flask through a spray tube with cooling and stirring, and after about 3 min, 15.3 g (94 mmol) of 2.6 g. dichloroaniline, 19.4 g (160 mmol) of nicotinamide, and 32.2 dichloromethane were added with stirring and cooling. After 30 min, 7.6948 g of 1,4-dichlorobenzene (internal standard for subsequent gas-liquid chromatographic analysis) and then the first prepared solution was added with stirring. The reaction mixture was allowed to warm slowly to room temperature and was analyzed by gas-liquid chromatography for the disappearance of the chlorosulfonyl starting material. After 4.5 hours, the mixture was diluted with 42.8 g of water and the resulting paste was filtered to recover the solids. The solids were re-pulped in a mixture of 41.7 g of water and 40.2 g of 2-propanol and re-recovered by filtration and then re-pulped in 13.2 g of 2-propanol and recovered again by filtration. The recovered solids were dried under reduced pressure at 40 ° C to obtain 26.9 g of 95 percent purity sulfonamide product (83 percent theory) as determined by quantitative H PLC using an external standard. There was another 4.8 percent of the theory product in the leaks.
12. Preparation of N- (2,6-dichlorophenyl) -7,8-dichloro-f1 .2.41-triazolori, 5-clpyrimidin-2-sulfonamide using sulphimimine catalyst without recovering A solution of 0.6 ml (8 mmol) of dimethyl sulfide in 65 ml of dichloromethane was cooled to -20 ° C and then 0.4 g (6 mmol) of chlorine was slowly sprayed with stirring and cooling to keep the temperature below -15 ° C. A mixture of 5.0 g (31 mmol) of 2,6-dichloroaniline and 6.3 g (49 mmol) of quinoline was then added with cooling and stirring to form a mixture of sulphilline catalyst, unreacted 2,6-dichloroaniline and quinoline. The mixture was allowed to warm to 0 ° C and 10 g (45 mmol) of 2-chlorosulfonyl-7,8-di-chlorotl-1-triazoloyl-c-pyrimidine were added with stirring and cooling. The mixture was allowed to warm to about 20 ° C and stir for about 16 hours. Then it was diluted with 50 ml of methanol and the solids that formed were collected by filtration, washed 2x30 ml with methanol, and dried to obtain 6.2 g (80 percent theory) of the title compound as a white solid having maximum uv at 210 and 270 nm. 1 H NMR [300 MHz] (D6-DMSO) ppm: 8.6 (brs, 1 H), 7.44 (d, 2H, J = 8.2), 7.32 (dd, 1 H, J = 8.2), 4.72 (q, 2H , J = 7.1), 1.50 (t, 3H, J = 7.1). The following compounds were prepared in a similar manner using the same sulfilimine catalyst: N- (2,6-dichlorophenyl) -7-fluoro-5-methoxy [1, 2,4] triazolo- [1,5-c] pyrimidine- 2-sulfonamide, a white-grayish solid obtained at approximately 21 percent yield: 'H NMR [300MHz] (D6-DMSO) ppm: 8.21 (s, 1 H), 7.44 (d, 2H, J = 8.3), 7.33 ( dd, 1 H, J = 8.3), 6.98 (d, 1 H, J = 1 .1), 4.28 (s, 3H);
N- (2,6-dichlorophenyl) -8-chloro-7-fluoro-5-ethoxy [1, 2,4] -triazolo [1, 5-c] pyrimidine-2-sulfonamide, a whitish solid obtained in approximately 85 percent yield; 'H NMR [300MHz] (CD3CN) ppm: 7.45 (d, 2H, J = 8.3), 7.34 (dd, 1 H, J = 8.3), 4.73 (q, 2H, J = 7.1), 1.51 (t, 3H , J = 7.1);
N- (2,6-dichlorophenyl) -7-chloro-5-ethoxy [1, 2,4] triazolo- [1, 5-c] pyrimidine-2-sulfonamide, a white solid obtained in about 90 percent of performance;
1H NMR [300MHz] (CD3CN) ppm: 8.29 (brs, 1 H), 7.47 (s, 1 H), 7.44 (d, 2H, J = 8.2), 7.33 (dd, 1 H, J = 8.2), 4.70 (q, 2H, J = 7.1), 1 .51 (t, 3H, J = 7.1);
N- (2,6-d-chlorofenyl) -7-fluoro-5- (1-methyletoxy) [1, 2, 4] -triazolo [1, 5-c] pyrimidine-5-sulfonamide, a brown solid -slight yellow obtained in approximately 77 percent yield; 1 H NMR [300MHz] (D6-DMSO) ppm: 7.82 (d, 2H, J = 8.2), 7.35 (d, 1 H, J = 8.2), 7.32 (s, 1 H), 5.47 (septet, 1 H , J = 6.1), 1 .46 (d, 6H, J = 6.1); 13C NMR [75.5MHz] (De-DMSO) ppm: 165.9, 161.9 (JC-F = 242.3), 157.1 (JC.F = 15.2),
# 10 150.4, 148.6 (JC-F = 26.0), 135.9, 130.3, 128.7, 86.4 (JC-F = 41.3), 76.6, 21.2.
13. Preparation of N-2-chlorophenyl-S-dimethylsulphimimine and its use as a catalyst to prepare N- (2-chlorophenyl) -4-methylbenzenesulfonamide A solution of 12.1 ml (0.17 mol) of dimethyl sulfide in 150 ml
dichloromethane was cooled to -10 ° C and then 10.8 g (0.15 mol) of chlorine was slowly sprayed with stirring and cooling to keep the temperature below -10 ° C. To this were added 19.1 g (0.15 mol) of 2-chloroaniline and then 38.7 g (0.30 mol) of quinoline with cooling and stirring to form the sulfilimine catalyst. An aliquot of 105 g
of the 272 g mixture was diluted with 200 ml of dichloromethane and then 25.5 g (0.20 mol) of 2-chloroaniline, 38.7 g (0.30 mol) of quinoline and finally 47.6 g (0.25 mol) of 4-methyl chloride. Benzenesulfonyl were added with cooling (-10 ° C) and stirring. The mixture was allowed to warm to room temperature and was stirred for 2 days.
The volatile components were then removed by w evaporation under reduced pressure and the oily residue obtained was dissolved in 300 ml of dichloromethane. The resulting solution was washed with 200 ml of 1 N aqueous hydrochloric acid and the wash water was back-extracted with 100 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated by evaporation under reduced pressure. The residue was dissolved in 175 ml of acetonitrile and re-precipitated by adding 200 ml of water slowly. The solids that were formed were collected by filtration, washed with 2-propanol, and dried under reduced pressure to obtain 44.7 g (64 percent theory) of the title compound as a whitish solid. 1 H NMR [300MHz] (CD3CN) ppm: 9.93 (s, 1 H), 7.60 (d, 2H, J = 8.2), 7.37 (d, 1 H, J = 7.4), 7.33 (d, 2H, J = 8.0), 7.24 (m, 2H), 7.16 (ddd, 1 H, J = 7.8, 5.2, 3.7), 2.33 (s, 3H); 13C NMR [75.5MHz] (D6-DMSO) ppm: 143.1, 137.5, 133.6, 130.1, 129.8, 129.5, 128.8, 127.6, 127.3, 126.9, 126.6, 20.9. 15. Sulphilimine-catalyzed preparation of N- (2,6-difluoro-phenyl) -5-methyl-1, 2,4-l-triazole, 5-alpyrimidine-2-sulfonamide A solution of 7.0 ml (0.096 mol) of dimethyl sulfide in 70 ml of dichloromethane was cooled to -10 ° C and then 5.5 g (0.078 mol) of chlorine
was slowly sprayed with stirring and cooling to keep the temperature below -10 ° C. To this was added with cooling and stirring 10.0 g (0.078 mol) of 2,6-difluoroaniline and then 50.0 g (0.39 mol) of quinoline to form the sulfilimine catalyst. An aliquot of 105 g of the 317 g mixture was diluted with 135 ml of dichloromethane and
Then 10.0 g (0.078 mol) of 2,6-difluoroaniline and 0.095 mol of 2-chlorosulfonyl-5-methyl [1,2,4] triazolo [1,5-a] pyrimidine were added with
* stirring and cooling to 0 ° C. After 20 min, 8.4 g (0.065 mol) of quinoline was added with stirring and the mixture was allowed to warm to room temperature overnight. The resulting mixture was filtered to collect the title compound as an insoluble light brown solid. The filtrate was washed with 150 ml of 1 N aqueous hydrochloric acid and the wash water was back-extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered to remove the magnesium sulfate. The magnesium sulfate was extracted
with 50 ml of acetonitrile, which was added to the filtrate. The filtrate was concentrated under reduced pressure and the solid residue obtained was pulped in water. The solids were collected by filtration and dried to obtain the title compound. The additional title compound was obtained from the filtrates. In all, 29.8 g of the title compound
(87 percent theory) were obtained as a white solid. 1 HN MR [300MHz] (CD3CN) ppm: 7.71 (d, 2H, J = 8.7), 7.53 (d, 2H, J = 8.7), 7.33 (tt, 1 H, J = 8.5, 6.1), 6.98 (dd) , 2H, J = 8.3, 8.2).
. Sulphurimine-catalyzed preparation of N- (2-methoxy-6- (trifluoromethyl) phenyl) -5-ethoxy-7-fluorori .2.41-azolo-p.5-clpyrimidine-2-sulfonamide A mixture containing about 10 mmol of N- (2-methoxy-6- (trifluoromethyl) phenyl-S, Sdmethyl-sulphonimine in about 17 ml of dichloromethane solution prepared as in Example 3A, omitting the recovery step, was diluted with 30 ml of dichloromethane and 10.0 g (52 mmol) of 2-methoxy-6- (trifluoromethyl) anililine, 4.6 (58 mmol) of pyridine, and 54 mmol of 2-chlorosulfonyl-5-ethoxy-7-fluoro [1, 2,4] - triazolo [1, 5-c] pyrimidine dissolved in 30 ml of dichloromethane were added sequentially with stirring at about -10 ° C. The mixture was allowed to stir overnight.A small amount of pyridine was added and The mixture was allowed to stir for a further 6 hours, the volatiles were then removed by evaporation under reduced pressure and the remaining thick paste was diluted with 30 ml. Methanol The solids present were recovered by filtration, re-pulped in methanol, and recovered again, washed with methanol and dried. The title compound was obtained as a yellow solid in 63 percent yield (14.9 g). 1 H NMR [300MHz] (CD3CN) ppm: 8.06 (1 s, 1 H), 7.47 (dd, 1 H, J = 8.5), 7.31 (d, 1 H, J = 8.1), 7.15 (d, 1 H , J = 8.4), 6.98 (d, 1 H, J = 1 .5), 4.73 (q, 2H, J = 7.1), 3.27 (s, 3H), 1.52 (t, 3H, J = 7.1).
16. Sulphurimine-catalyzed preparation of N- (2-chloro-4- (1-methyletoxy) -3-pyridinyl) -5-ethoxy-7-f luorof 1.2.4ltriazolo-f1.5-cl-pyrimidine-2-sulfonamide A mixture containing about 10 mmol of N- (2-chloro-4- (1-methylethoxy) -3-pyridinyl-S, S-dimethylsulphimimine in about 18 ml of dichloromethane solution prepared as in Example 3A omitting the recovery step , was diluted with 45 ml of dichloromethane and 4.5 g (24 mmol) of 3-amino-2-chloro-4- (1-methylethoxy) -pyridine, 3.2 g (41 mmol) of pyridine, and 36 mmol of 2-chlorosulfonyl 5-Ethoxy-7-fluoro [1, 2,4] -triazolo [1,5-cjpyrimidine dissolved in 19 ml of dichloromethane were added sequentially with stirring and cooling to about -10 [deg.] C. The mixture was allowed to stir The volatiles were then removed by evaporation under reduced pressure.The solid residue was dissolved in acetonitrile and methanol 1.1 and 0.5N aqueous hydrochloric acid was added until solids were recovered by filtration, washed 2x75 ml with water and dried to obtain 11.0 g (73 percent theory) of the title compound as a white solid. Another 1 .7 g (1 1 percent theory) of product was obtained from the aqueous phases by extraction. 1 H NMR [300MHz] (CD3CN) ppm: 10.6 (s, 1 H), 8.16 (d, 1 H, J = 5.8), 7.41 (s, 1 H), 7.1 1 (d, 1 H, J = 5.9 ), 4.71 (d, 1 H, J = 7.0), 4.56 (septet, 1 H, J = 6.0), 1.45 (t, 3H, J = 7.0), 0.82 (d, 6H, J = 6.0).
17. Sulphurimine catalyzed preparation of N- (5-bromo-2-pyrimidinyl) -4-methyl-phenylsulfonamide A mixture containing approximately 17 mmol of N-5-bromo-2-pyridinyl-S, S-dimethylsulphimin in approximately 30 ml of dichloromethane solution prepared as in Example 3A omitting the recovery step, was diluted with 43 ml of dichloromethane and then 10.0 g (58 mmol) of 2-amino-5-bromopyridine, 5.5 g (70 mmol) of pyridine, and 14.2 (74 mmol) of 4-methyIbenzenesulfonyl chloride were added sequentially with stirring and cooling to -10 ° C. The mixture was allowed to warm to 20 ° C with stirring. A white precipitate formed quickly. 1.6 g (20 mmol) of additional pyridine was added and the mixture allowed to settle for 3 days. Dichloromethane (25 ml) was added to dissolve all solids and the resulting solution was washed with 150 ml of 0.1 N aqueous hydrochloric acid. The aqueous layer was back-extracted with dichloromethane and the combined organic phases were dried over magnesium sulfate and concentrated by evaporation under reduced pressure. The yellow solid residue was recrystallized from 175 ml of acetonitrile and the resulting yellow solid (a first round of 8.3 g and a second round of 1.5 g) was recovered to obtain the title compound (41 percent theory). 1 H NMR [300MHz] (D6-DMSO) ppm: 1 1 .26 (s, 1 H), 8.26 (d, 1 H, J = 2.4), 7.87 (dd, 1 H, J = 8.8, 2.4) , 7.78 (d, 2H, J = 8.2), 7.34 (d, 2H, J = 8.1), 7.03 (d,
1 H, J = 8.8), 2.31 (s, 3H); 13C N MR [75.5MHz] (D6-DMSO) ppm: 150.4, 148.3,
143. 4, 140.8, 137.2, 129.5, 127.0, 1 13.7, 1 13.2, 20.9.
18. Sulphurimine catalyzed preparation of N- (2-methyl-6-nitro-phenyl) -4-chloro-3-nitrophenylsulfonamide A mixture containing about 22 mmol of N- (2-methyl-6-nitrophenyl) -S, S-dimethyl-sulphonimine in about 25 ml of dichloromethane solution prepared as in Example 3A, omitting the recovery step, was diluted with 15 ml of dichloromethane and then 11.0 g (72 mmol) of 2-methyl-6-nitroaniline, 15 g (120 mmol) of quinoline and, 24 g (95 mmol) of 4-chloro-3-nitrobenzenesulfonyl chloride were added sequentially with stirring and cooling to -10 ° C. The mixture was allowed to slowly warm to 20 ° C and was stirred overnight. 6.0 g (76 mmol) of additional pyridine were added in two equal portions. After a short time, 100 ml of acetonitrile was added and the resulting solution was washed with 1N aqueous hydrochloric acid. The aqueous phase was extracted with 50 ml of dichloromethane and then 50 ml of acetonitrile. The combined organic phases were dried over magnesium sulfate (washing the magnesium sulfate with 2x50 ml of acetonitrile), and
The combined organic solutions were concentrated by evaporation under reduced pressure. The resulting oil was dissolved in warm 2-propanol and re-precipitated by adding 200 ml of 1 N aqueous hydrochloric acid. The resulting solids were recovered by filtration, washed with 2-propanol, and dried to obtain 18.5 g (66 g).
percent theory) of the title compound. 1 H NMR [300MHz] (CD3CN) ppm: 7.71 (d, 2H, J = 8.7), 7.53 (d, 2H, J = 8.7), 7.33 (tt, 1 H, J = 8.2, 6.1), 6.98 (dd) , 2H, J = 8.3, 8.2).
19. Sulphurimine-catalyzed preparation of N- (4-bromo-1-methyl-5-15 pyrazolyl) -5-ethoxy-7-fluoro [1,24-triazolo-p, 5-clpyrimidine-2-sulfonamide A mixture containing approximately 53 mmol of N- (4-bromo-1-methyl-5-pyrrazolyl) -S, S-dimethylsulphimimine in about 28 ml of dichloromethane solution prepared in Example 7 omitting the recovery step, cooled to -10 ° C and 1.0 g (5.7 mmol) of 5-amino-4-bromo-1-20 methylpyrazole, 0.54 g (6.8 mmol) of pyridine, 1.8 mmol of 2-chlorosulfonyl-5-ethoxy-7-fluoro- [1, 2,4] triazolo [1, 5-c] pyrimidine, and 5 ml of dichloromethane were added sequentially with stirring and cooling to about -10 ° C. The mixture was allowed to stir at room temperature for 2 days. The solids present were recovered by filtration, washed with a small amount of 2-propoanol, and dried to obtain 5.7 g of the title compound as a
• ß »white solid. A purer sample amounting to 4.6 g (26 percent theory) was obtained by dissolving this in dimethyl sulfoxide and then adding water to re-precipitate it. 5 1 H NMR [300MHz] (CD3CN) ppm: 10.9 (s, 1 H), 7.86 (s, 1 H), 7.36 (d, 1 H, J = 0.72), 4.68 (q, 2H, J = 7.1 ), 3.68 (s, 3H), 1 .46 (t, 3H, J = 7.1).
. Sulphurimine catalyzed preparation of N- (2,6-difluoro-phenyl) -4-chlorobenzenesulfonamide A solution of 7.0 ml (96 mmol) of dimethyl sulfide in 70 ml of dichloromethane was prepared in a round bottom flask and cooled to - 10 ° C. Chlorine gas (5.5 g, 78 mmol) was added to the vapor space of the flask through a spray tube with cooling and stirring. After a short period, 10.0 g (78 mmol) of 2,6-difluoroaniline and
Then 50 g (390 mmol) of quinoline were added with stirring and cooling. An aliquot of 109 g of the obtained 317 g mixture was diluted with 15 ml of dichloromethane and 13.5 g (105 mmol) of 2,6-difluoroaniline and then 27.3 g (125 mmol) of 4-chlorobenzenesulfonyl chloride were added with stirring and cooling at 0 ° C.
The mixture was stirred cold for 1 hour, an additional 8.4 g (65 mmol) of quinoline was added, and the mixture was allowed to warm to room temperature and stir overnight. The acetonitrile was added to dissolve the solids present and the resulting solution was washed with 1 N aqueous hydrochloric acid. The aqueous phase was extracted with a
mixture of 70 ml of dichloromethane and 50 ml of acetonitrile. The organic phases were combined, diluted with 75 ml of acetonitrile, and dried over magnesium sulfate (washing the magnesium sulfate with 2x25 ml of acetonitrile). The combined organics were concentrated by evaporation under reduced pressure. The solid residue was dissolved in
Aqueous methanol to 90 percent and the product was precipitated by adding 300 ml of water. The solids were collected by filtration, washed with water and dried to obtain 30.5 g of the title compound as a light brown solid. Another 4.0 g of the title compound were obtained
* of the filtrate for a total of 34.5 g (87 percent theory). 10 1 H NMR [300MHz] (CD3CN) ppm: 7.71 (d, 2H, J = 8.7), 7.53 (d, 2H, J = 8.7), 7.33 (tt, 1 H, J = 8.5, 6.1 Hz), 6.98 (dd, 2H, J = 8.3, 8.2).
Claims (19)
- REIVI NDICATIONS 1 . A substituted N-arylsulphimimine compound of the formula: 5 AR'- N = S \ R 'wherein R represents methyl, ethyl or n-propyl; * R 'represents R, benzyl or phenyl; 10 or R and R 'together represent tetramethylene; and AR 'represents an aromatic portion selected from d) a substituted phenyl portion of the formula: wherein A represents F, Cl, Br, NO2, CN, dC fluoroalkyl, CO2 (C? -C4 alkyl), CONH (C? -C4 alkyl), CON (C? -C4 alkyl) 2, SO2 (C? -C alkyl), or SO2 (C? -C fluoroalkyl); B represents C? -C4 alkyl, F, Cl, Br, O (C? -C alkyl), O (C? -C4 fluoroalkyl), S (C? -C alkyl), S (C? -C fluoroalkyl), N (C? -C alkyl) 2; or phenyl, phenoxy or phenylthio each optionally possessing 1 to 3 substituents selected from the group consisting of F, Cl, Br, CN, CF3, NO2, and CH3; and D and J each independently represents H or CH3 with the proviso that at least one of D and J represents H; e) a substituted 3-pyridinyl portion of the formula: wherein L and M each independently represent H, C? -C alkyl, d- C4 fluoroalkyl, O (C? -C4 alkyl), O (C1-C fluoroalkyl), O (C2-C alkoxyalkyl), 0 (C3 -C alkenyl), 0 (C3-C4 alkynyl), S (dC alkyl), S (dC fluoroalkyl), SO2 (C? -C4 alkyl), SOz (dC fluoroalkyl), F, Cl, Br, I, CN, NO2, C6H5, CO2 (C? -C4 alkyl), CO2 (C3-C4 alkenyl), CO2 (C3-C alkynyl), CON (C1-C4 alkyl) 2, or CONH (C? - C alkyl), with the proviso that not more than one of L and M represents H; and T represents H, F, Cl, Br, I, CH3, or CF3; or c) a 3-, 4- or 5-pyrazolyl moiety substituted with a d-C3 alkyl group in the 1-position, with at least one Cl, Br, I or CF3, and optionally, with an OCH3 or CH3 group.
- 2. A compound according to claim 1, wherein R and R 'each represents methyl.
- 3. A compound according to claim 1, wherein AR 'is a substituted phenyl portion and A represents F, Cl, Br, CF3, NO2, or CO2CH3; B represents F, Cl, Br, CH 3, OCH 3; D represents H or CH 3; and J represents H. 5
- 4. A compound according to claim 1 wherein AR 'is a substituted pyridinyl moiety, wherein T represents H and a) M represents Cl, Br, or CF3 and L represents O (d-C3 alkyl) or O (C? -C3 alkenyl) or b) M represents F and L represents C1-C2 alkyl.
- 5. A compound according to claim 1, wherein AR 'is a substituted pyrazolyl moiety selected from 1-methyl-4-halo-3-pyrazolyl, 1-methyl-4-halo-5-pyrazolyl and 1 - ethyl-3- (trifluoromethyl) -5- (methyl, methoxy, or halo) -4-pyrazolyl.
- 6. A compound according to claim 3, which is one of S, S-dimethyl-N- (2,5-dichloro-3-methylphenyl) sulphonamine, S, S-dimethyl-N- (2, 5- 15 dichlorophenyl) sulphimimine, S, S-dimethyl-N- (2,6-difluorophenyl) sulphimimine, and S, S-dimethyl-N- (2-methoxycarbonyl-6-chlorophenyl) sulphonimine.
- 7. A process for the preparation of an N-arylarylsulfonamide compound of the formula: Q-SO2NH-AR 20 wherein Q and AR each independently represent an aromatic hydrocarbyl or an aromatic heterocyclyl portion which comprises combining a sulfonyl of Formula: Q-SO2Cl wherein Q is as defined above with an amine compound of Formula: AR- N H2 wherein AR is as defined above in the presence of an aromatic tertiary amine base and a catalytic amount added with an N-arylsulphimine compound of Formula I: AR'- N = S \ R 'wherein R represents methyl, ethyl or n-propyl; R 'represents R, benzyl or phenyl; or R and R 'together represent tetramethylene; and AR 'represents a portion of aromatic hydrocarbyl or aromatic heterocyclyl.
- 8. A process according to claim 7, wherein AR 'of the N-arylsulphimin compound is selected to be identical to AR in the amine compound.
- 9. A process according to claim 8, wherein the N-arylsulphimin compound is a compound of any of claims 1 to 6.
- 10. A process according to claim 8, wherein AR is selected from 2,6-dichloro-3-methylphenyl, 2,6-diclphenyl, 2,6-difluorophenyl, and 2-methoxycarbonyl-6-chlorophenyl. eleven .
- A process according to claim 8, wherein Q represents a portion of substituted phenyl, substituted pyridinyl, [1, 2,4] triazolo [1, 5-c] primidin-2-yl substituted, [1, 2.4 ] substituted triazolo [1, 5-a] pyrimidine-2-yl, or [1, 2,4] triazolo [1, 5-a] pyridine-2-yl substituted.
- 12. A process according to claim 1, wherein the substituents are selected from F, Cl, Br, I, NO2, CN, O (C3-C ahenynyl), or O (C3-C4 alkynyl); d-C4 alkyl, O (C? -C4 alkyl), N (dC alkyl) 2, S (C? -C4 alkyl), SO2 (d-C4 alkyl), CO2 (C? -C alkyl), CONH (C ? -C4 alkyl), or CON (C? -C alkyl) 2 (each alkyl optionally mono a completely substituted with fluorine); or phenyl or phenoxy (each optionally possessing 1 to 3 substituents selected from the group consisting of f, Cl, Br, CN, CF3, NO2, and CH3).
- 13. A process according to claim 7, wherein the sulfonyl chloride compound is selected from 2-chlorosulfonyl-5-ethoxy-7- 15 fluoro [1, 2,4] triazolo [1, 5-c] pyrimidine , 2-chloro-sulfonyl-5-methoxy-8-fluoro [1, 2,4] triazolo [1, 5-c] pyrimidine, 2-chlorosulfonyl-5-methoxy-7-methyl [1, 2,4] triazolo [1, 5-c] pyrimidine, 2-chlorosulfonyl-5-ethoxy-7-methyl [1, 2,4] triazolo- [1, 5-c] primidine, 2-chlorosulfonyl-5-methyl [1, 2 , 4] triazolo- [1, 5-a] pyrimidine, 2-chlorosulfonyl-5,7-dimethoxy [1, 2,4] triazolo [1, 5- 20 ajpyrimidine, 2-chlorosulfonyl-5,7-dimethyl] , 2,4] -triazolo [1, 5-a] pyrimidine, 2-chlorosulfonyl-5-methoxy-7-methyl [1, 2,4] triazolo [1, 5-a] pyridine, and 2-chlorosulfonyl-5 -methoxy-8-chloro [1, 2,4] triazolo [1, 5-a] pyridine.
- 14. A process according to claim 7, wherein the aromatic tertiary amine base is selected from pyridine, a picoline, 25 nicotinamide and quinoline.
- 15. A process according to claim 7, wherein the sulfilimine catalyst is prepared essentially immediately before use and is used in the form of the reaction mixture in which it was prepared or in a partially purified form.
- 16. A process according to claim 7, wherein the temperature is maintained at -20 to 50 ° C.
- 17. A process according to claim 7, wherein the amount of catalyst used is between 2 to 30 percent mole of the aromatic sulfonyl chloride compound.
- 18. A method of using an N-arylsulphimine compound of any of claims 1 to 6 to catalyze the reaction between an aromatic sulfonyl chloride compound of the formula: Q-SO2CI wherein Q represents a hydrocarbyl portion aromatic or aromatic heterocyclyl with an aromatic amine compound of the formula: ff AR-NH2 wherein AR represents an aromatic hydrocarbyl or aromatic heterocyclyl portion to obtain an N-arylarylsulfonamide compound of the Formula: Q- SO2NH-AR in where Q and AR are as defined above.
- 19. A method of use according to claim 18, wherein AR 'of the N-arylsulphimin compound is selected to be identical to AR 25 of the aromatic amine compound.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US030896 | 1996-11-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA98005645A true MXPA98005645A (en) | 1999-05-31 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5973148A (en) | N-arylsulfilimine compounds and their use as catalysts in the preparation of N-arylarylsulfonamide compounds | |
KR101111014B1 (en) | An improved process for the preparation of n-[1,2,4]triazolopyrimidin-2-ylaryl sulfonamides | |
Elgemeie et al. | Synthesis of some novel α-cyanoketene S, S-acetals and their use in heterocyclic synthesis | |
CN111315742B (en) | Process for preparing aminopyrimidine derivatives | |
EP0537611B1 (en) | Process for the preparation of substituted N-(aryl)-1,2,4-triazolopyrimidine-2-sulfonamides | |
Wu et al. | Copper-Catalyzed, Aerobic Synthesis of N H-Sulfonimidamides from Primary Sulfinamides and Secondary Amines | |
Ramos et al. | ZnEt2 as a Precatalyst for the Addition of Alcohols to Carbodiimides | |
MXPA98005645A (en) | N-arylsulfilimine compounds and their use as catalysts in the preparation of n-arylarylsulfonamide compounds | |
CA2241263C (en) | N-arylsulfilimine compounds and their use as catalysts in the preparation of n-arylarylsulfonamide compounds | |
JP4838146B2 (en) | Method for preparing triazolopyrimidine | |
Coe et al. | Reactions of polyfluoropyridines with bidentate nucleophiles: attempts to prepare deazapurine analogues | |
EP1932846B1 (en) | Method for producing sulfonyl chloride compound | |
Srivastava et al. | A Solid Phase Approach to Substituted Pyrimidines and Their Conversion into Condensed Heterocycles for Potential Use in Combinatorial Chemistry | |
RU2241710C1 (en) | Method for preparing substituted pyrido[1,2-a][1,3]-benzimidazoles | |
EP3669869A1 (en) | Drug for treating tumor diseases, and having antibacterial, antivirus and anti-inflammatory effects | |
EP0188225A1 (en) | Process for the preparation of herbicidal sulfonamides derived from substituted 2-amino-1,2,4 triazolo (1,5-a) pyrimidines and novel intermediates provided therein | |
CZ20024130A3 (en) | Process for preparing pyrazolopyrimidinones | |
CN117659021A (en) | Method for preparing propyrisulfuron | |
KR20050003080A (en) | 3,4-Dihydroquinazoline Derivatives and Process for the Preparation Thereof | |
NZ275334A (en) | Process for synthesis of 2-amino-3,5-dihydro-7-substituted-4h pyrrolo[3,2-d]pyrimidin-4-one derivatives | |
NZ329428A (en) | N-phenylsuponamides and o-aminophenyl ketones as intermediates in the manufacture of sulfamoyl urea herbicides | |
JP2007197395A (en) | Method for producing sulfonylurea compound |