NL8001176A - PYRIDYL ESTERS AND THIO-ESTERS OF AMINO ACIDS, INTERIM PRODUCTS FOR THE SAME AND METHODS FOR PREPARING AND USING THESE COMPOUNDS. - Google Patents
PYRIDYL ESTERS AND THIO-ESTERS OF AMINO ACIDS, INTERIM PRODUCTS FOR THE SAME AND METHODS FOR PREPARING AND USING THESE COMPOUNDS. Download PDFInfo
- Publication number
- NL8001176A NL8001176A NL8001176A NL8001176A NL8001176A NL 8001176 A NL8001176 A NL 8001176A NL 8001176 A NL8001176 A NL 8001176A NL 8001176 A NL8001176 A NL 8001176A NL 8001176 A NL8001176 A NL 8001176A
- Authority
- NL
- Netherlands
- Prior art keywords
- pyridyl
- methyl
- hydrogen atom
- formula
- phenoxy
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 34
- 238000000034 method Methods 0.000 title claims description 17
- 150000007970 thio esters Chemical class 0.000 title description 5
- 150000001413 amino acids Chemical class 0.000 title description 3
- -1 cyano, ethynyl Chemical group 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 229910052731 fluorine Chemical group 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 241000607479 Yersinia pestis Species 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 230000004308 accommodation Effects 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- 239000000243 solution Substances 0.000 description 21
- 239000004474 valine Substances 0.000 description 21
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 20
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 241000238876 Acari Species 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 241000238631 Hexapoda Species 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- LGNROYCDLXXDRN-UHFFFAOYSA-N (6-phenoxypyridin-2-yl)methanol Chemical compound OCC1=CC=CC(OC=2C=CC=CC=2)=N1 LGNROYCDLXXDRN-UHFFFAOYSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- LOQOJKZPSJTLLG-UHFFFAOYSA-N 2-hydroxy-2-(6-phenoxypyridin-2-yl)acetonitrile Chemical compound N#CC(O)C1=CC=CC(OC=2C=CC=CC=2)=N1 LOQOJKZPSJTLLG-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- YKSHSSFDOHACTC-UHFFFAOYSA-N 2-[2-chloro-4-(trifluoromethyl)anilino]-3-methylbutanoic acid Chemical compound CC(C)C(C(O)=O)NC1=CC=C(C(F)(F)F)C=C1Cl YKSHSSFDOHACTC-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000255925 Diptera Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- NYPJDWWKZLNGGM-UHFFFAOYSA-N fenvalerate Chemical compound C=1C=C(Cl)C=CC=1C(C(C)C)C(=O)OC(C#N)C(C=1)=CC=CC=1OC1=CC=CC=C1 NYPJDWWKZLNGGM-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- BITJWWCKVCSAIQ-UHFFFAOYSA-N methyl 2-[2-chloro-4-(trifluoromethyl)anilino]-3-methylbutanoate Chemical compound COC(=O)C(C(C)C)NC1=CC=C(C(F)(F)F)C=C1Cl BITJWWCKVCSAIQ-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VROZCADDFUUKKS-NSHDSACASA-N (2s)-2-(2-chloro-4-methylanilino)-3-methylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC1=CC=C(C)C=C1Cl VROZCADDFUUKKS-NSHDSACASA-N 0.000 description 1
- AJWAECPVBMQFSX-NSHDSACASA-N (2s)-3-methyl-2-(4-methylanilino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC1=CC=C(C)C=C1 AJWAECPVBMQFSX-NSHDSACASA-N 0.000 description 1
- FZRBKIRIBLNOAM-UHFFFAOYSA-N (E,E)-2-propynyl 3,7,11-trimethyl-2,4-dodecadienoate Chemical compound CC(C)CCCC(C)CC=CC(C)=CC(=O)OCC#C FZRBKIRIBLNOAM-UHFFFAOYSA-N 0.000 description 1
- ARAFEULRMHFMDE-UHFFFAOYSA-N 1,3-oxazolidine-2,5-dione Chemical compound O=C1CNC(=O)O1 ARAFEULRMHFMDE-UHFFFAOYSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- DLULJAUWRRKBML-UHFFFAOYSA-N 2-[2-fluoro-4-(trifluoromethyl)anilino]-3-methylbutanoic acid Chemical compound CC(C)C(C(O)=O)NC1=CC=C(C(F)(F)F)C=C1F DLULJAUWRRKBML-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
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- FVIPZEZSEOZNTN-UHFFFAOYSA-N 5,6-dimethylpyridin-3-amine Chemical compound CC1=CC(N)=CN=C1C FVIPZEZSEOZNTN-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000254173 Coleoptera Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 241000256257 Heliothis Species 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241001466007 Heteroptera Species 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 241000238887 Ornithodoros Species 0.000 description 1
- 241000238814 Orthoptera Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 241001674048 Phthiraptera Species 0.000 description 1
- ISRUGXGCCGIOQO-UHFFFAOYSA-N Rhoden Chemical compound CNC(=O)OC1=CC=CC=C1OC(C)C ISRUGXGCCGIOQO-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000916145 Tarsonemidae Species 0.000 description 1
- 241001454295 Tetranychidae Species 0.000 description 1
- 241000625014 Vir Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 1
- 229960005286 carbaryl Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- WCMMILVIRZAPLE-UHFFFAOYSA-M cyhexatin Chemical compound C1CCCCC1[Sn](C1CCCCC1)(O)C1CCCCC1 WCMMILVIRZAPLE-UHFFFAOYSA-M 0.000 description 1
- OEBRKCOSUFCWJD-UHFFFAOYSA-N dichlorvos Chemical compound COP(=O)(OC)OC=C(Cl)Cl OEBRKCOSUFCWJD-UHFFFAOYSA-N 0.000 description 1
- 229950001327 dichlorvos Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- FYQGBXGJFWXIPP-UHFFFAOYSA-N hydroprene Chemical compound CCOC(=O)C=C(C)C=CCC(C)CCCC(C)C FYQGBXGJFWXIPP-UHFFFAOYSA-N 0.000 description 1
- 229930000073 hydroprene Natural products 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229930001540 kinoprene Natural products 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930002897 methoprene Natural products 0.000 description 1
- 229950003442 methoprene Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- BUYMVQAILCEWRR-UHFFFAOYSA-N naled Chemical compound COP(=O)(OC)OC(Br)C(Cl)(Cl)Br BUYMVQAILCEWRR-UHFFFAOYSA-N 0.000 description 1
- 239000000025 natural resin Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960000490 permethrin Drugs 0.000 description 1
- RLLPVAHGXHCWKJ-UHFFFAOYSA-N permethrin Chemical compound CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- VEMKTZHHVJILDY-FIWHBWSRSA-N resmethrin Chemical compound CC1(C)[C@H](C=C(C)C)C1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-FIWHBWSRSA-N 0.000 description 1
- 229940108410 resmethrin Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
*. i s*. i s
Pyridylesters en thio-esters van aminozuren, tussenprodukten hiervoor en werkwijzen voor het bereiden en toepassen van deze verbindingen.Pyridyl esters and thioesters of amino acids, intermediates for these and methods of preparing and using these compounds.
De uitvinding heeft betrekking op nieuwe esters en thio-esters van aminozuren en op nieuwe tussenprodukten hiervoor en op werkwijzen voor het bereiden van deze esters en van preparaten die deze esters bevatten, alsmede op de onder toepassing van deze 5 laatste werkwijze verkregen gevormde preparaten en op een werkwijze voor het bestrijden van ongedierte.The invention relates to new esters and thio esters of amino acids and to new intermediates therefor and to processes for the preparation of these esters and of preparations containing these esters, as well as to the formed preparations obtained by the latter process and to a method of pest control.
De esters en thio-esters van de uitvinding hebben formule 5, waarin R' een waterstof- of fluoratoom, W zuurstof of zwavel, t nul, een of twee, Y een waterstof-, chloor- of fluor-10 atoom, Z een trifluormethylgroep, een chloor- of fluoratoom, een methoxy-, methyl-, ethyl-, difluormethoxy- of trifluormethoxygroep,The esters and thioesters of the invention have formula 5, wherein R 'is a hydrogen or fluorine atom, W oxygen or sulfur, t zero, one or two, Y is a hydrogen, chlorine or fluorine atom, Z is a trifluoromethyl group , a chlorine or fluorine atom, a methoxy, methyl, ethyl, difluoromethoxy or trifluoromethoxy group,
Rg een waterstofatoom, een methyl-,ethyl-, acetyl- of formylgroep en R^ een waterstofatoom, een cyaan-, ethynyl- of methylgroep, alsmede de zouten daarvan met sterke anorganische en organische 15 zuren.Rg is a hydrogen atom, a methyl, ethyl, acetyl or formyl group and Rg is a hydrogen atom, a cyano, ethynyl or methyl group, as well as its salts with strong inorganic and organic acids.
De verbindingen volgens de uitvinding met formule 5, waarin de substituenten en symbolen die de hiervoor aangegeven betekenissen hebben, zijn bruikbare middelen voor het bestrijden van ongedierte, zoals insecten en mijten.The compounds of the invention of formula 5, wherein the substituents and symbols having the meanings indicated above, are useful agents for controlling pests, such as insects and mites.
20 In de hierna volgende beschrijving en conclusies heeft elk van de substituenten en symbolen R1, R^, R^, W, Y, Z en t de hiervoor aangegeven betekenissen, tenzij anders vermeld.In the following description and claims, each of the substituents and symbols R1, R1, R2, W, Y, Z and t has the meanings indicated above, unless otherwise stated.
De verbindingen volgens de uitvinding met formule 5 kunnen volgens schema A afgebeeld op het formuleblad worden ge-25 synthetiseerd.The compounds of the invention of formula 5 can be synthesized according to scheme A depicted on the formula sheet.
Volgens de algemene praktijk van deze synthese laat men een zuur of een zout of zuurchloride hiervan met een alcohol met 800 1 1 76 2 formule 2 reageren tot de carbonzuurester met formule 6. Zo kan men bijvoorbeeld een zuurchloride van het zuur met formule 1 in een organisch oplosmiddel, zoals diethylether, in aanwezigheid van triethylamine laten reageren met een alcohol met formule 2. Volgens 5 een andere uitvoeringsvorm laat men een zuur met formule 1 en een alcohol met formule 2 in een organisch oplosmiddel, zoals methyleen-chloride, in aanwezigheid van U-dimethylaminopyridine en dicyclo-hexylcarbodiimide reageren tot een ester met formule 6. Volgens een andere uitvoeringsvorm worden de esters met formule 6 ge-10 synthetiseerd door reactie van een zuur met formule 1 met fosgeen in aanwezigheid van een ether, zoals 1,^-dioxan, onder vorming van het overeenkomstige oxazolidine-2,5-dion, dat men daarna met een alcohol met formule 2 laat reageren tot de overeenkomstige ester met formule 6. Volgens een andere synthese laat men een zuur met 15 formule 1 of een zout daarvan met het bromide, chloride of mesylaat van de alcohol met formule 2 reageren tot een ester met formule 6.According to the general practice of this synthesis, an acid or a salt or acid chloride thereof is reacted with an alcohol of 800 1 1 76 2 formula 2 to form the carboxylic acid ester of formula 6. For example, an acid chloride of the acid of formula 1 can be organic solvent, such as diethyl ether, in the presence of triethylamine, react with an alcohol of the formula 2. In another embodiment, an acid of the formula 1 and an alcohol of the formula 2 are left in an organic solvent, such as methylene chloride, in the presence of U-dimethylaminopyridine and dicyclohexylcarbodiimide react to form an ester of formula 6. In another embodiment, the esters of formula 6 are synthesized by reaction of an acid of formula 1 with phosgene in the presence of an ether such as 1, - dioxane, to form the corresponding oxazolidine-2,5-dione, which is then reacted with an alcohol of formula 2 to form the corresponding ester of formula 6. In another synthesis, an acid of formula 1 or a salt thereof is reacted with the bromide, chloride or mesylate of the alcohol of formula 2 to form an ester of formula 6.
De toegepaste uitgangsmaterialen met formule 1 zijn beschreven door Henrick en Garcia in het Duitse Offenlegungs-20 schrift 28 12 169· De alcoholen met formule 2 kunnen worden verkregen op de wijze als beschreven door Malhotra en Ricks in het Duitse Offenlegungsschrift 28 10 881 en door Maeda en Hirose, CA 81 13596k en 80 59873s, alsmede in de daarin geciteerde litera-tuurplaatsen.The starting materials of the formula I used are described by Henrick and Garcia in German Offenlegungs-20 28 28 169 · The alcohols of formula 2 can be obtained in the manner described by Malhotra and Ricks in German Offenlegungsschrift 28 10 881 and by Maeda and Hirose, CA 81 13596k and 80 59873s, as well as in the literature references cited therein.
25 Volgens weer een andere uitvoeringsvorm kan men ver bindingen met formule 5 verkrijgen door reactie van een amine met formule 3 met een cC -halogeenester met formule U (waarin X een broom- of chlooratoom voorstelt).In yet another embodiment, compounds of formula 5 can be obtained by reacting an amine of formula 3 with a cC-halogen ester of formula U (wherein X represents a bromine or chlorine atom).
De reactie van een amine met formule 3 en een halogeen-30 ester met formule 4 wordt in het algemeen al of niet in een organisch oplosmiddel, zoals hexamethyl — fosfortriamide, tetra-hydrofuran, dimethylformamide, dimethylsulfoxyde enz., uitgevoerd.The reaction of an amine of formula 3 and a halogen-ester of formula 4 is generally carried out in an organic solvent or not, such as hexamethylphosphoric triamide, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, etc.
De halogeenestezs met formule U kunnen worden verkregen door reactie van een zuurhalogenide daarvan met een alcohol met formule 2. 35 De thio-esters met formule 5 kunnen worden bereid door reactie van bijvoorbeeld het natriumzout van een thiozuur dat 800 1 1 76 3 >i' 4 overeenkomt met formule 1 met het bromide of mesylaat van een alcohol met formule 2.The haloestezes of the formula U can be obtained by reacting an acid halide thereof with an alcohol of the formula 2. The thioesters of the formula 5 can be prepared by reacting, for example, the sodium salt of a thioic acid containing 800 1 1 76 3> 1 '. 4 corresponds to Formula 1 with the bromide or mesylate of an alcohol of Formula 2.
De verbindingen volgens de uitvinding met formule 5 bezitten een of een aantal asymmetrische koolstofatomen. Het zal 5 duidelijk zijn dat de uitvinding zowel elk van de optische isomeren als racemische mengsels daarvan omvat. In de hierna volgende voorbeelden werden de verbindingen verkregen in de vorm van een race-misch mengsel, tenzij anders aangegeven.The compounds of the formula according to the invention have one or more asymmetric carbon atoms. It will be understood that the invention encompasses both of the optical isomers and racemic mixtures thereof. In the following examples, the compounds were obtained in the form of a racemic mixture, unless otherwise indicated.
Binnen het kader van de uitvinding vallen eveneens de IQ zouten van de verbindingen met formule 5· Deze zouten worden gevormd met behulp van sterke anorganische of organische zuren, zoals zoutzuur, zwavelzuur, fosforzuur, p-tolueensulfonzuur, p-benzeensulfonzuur, methaansulfonzuur, Lewiszuur en overeenkomstige zuren. Vele van de verbindingen met formule 5 zijn oliën, die je; terwille van het gemak van het hanteren en het samenstellen en ter verkrijging van een uitstekende stabiliteit worden omgezet in de zouten. Deze zouten zijn op dezelfde wijze als de verbindingen met formule 5 bruikbaar voor het bestrijden van ongedierte.Also within the scope of the invention are the IQ salts of the compounds of formula VI. These salts are formed using strong inorganic or organic acids, such as hydrochloric acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid, p-benzenesulfonic acid, methanesulfonic acid, Lewis acid and corresponding acids. Many of the compounds of formula 5 are oils that you; for ease of handling and assembly and to obtain excellent stability are converted to the salts. These salts are useful in the same manner as the compounds of formula 5 for pest control.
De verbindingen volgens de uitvinding met formule 5» 20 alsmede de zouten daarvan, zijn bruikbare middelen voor het bestrijden van ongedierte, in het bijzonder van insecten en mijten.The compounds of the formula (20) according to the invention, as well as the salts thereof, are useful agents for controlling pests, in particular insects and mites.
Voor het toepassen van de verbindingen volgens de uitvinding met formule 5 voor het bestrijden van insecten en mijten ter bescherming van landbouwgewassen, bijvoorbeeld sojabonen, katoen, alfalfa, 25 enz., brengt men ëën of een aantal verbindingen volgens de uitvinding met formule 5, en/of de zouten daarvan, desgewenst tezamen met een drager, in een doeltreffende hoeveelheid op de te behandelen gebieden. De eventueel toegepaste drager kan zowel vloeibaar als vast zijn en omvat toevoegsels, zoals bevochtigende midde-30 len, dispergeermiddelen en andere oppervlakte-aktieve middelen. De verbindingen volgens de uitvinding met formule 5 kunnen opgenomen worden in preparaten, zoals bevochtigbare poeders, oplossingen, verstuifbare preparaten, korrels, emulgeerbare geconcentreerde preparaten enz.. Voorbeelden van geschikte vaste dragers zijn 35 natuurlijke en synthetische silicaten en kleisoorten, koolprodukten en houtskoolkorrels, natuurlijke en synthetische harsen, wassen enz..For the use of the compounds of the invention of formula 5 to control insects and mites to protect agricultural crops, for example soybeans, cotton, alfalfa, etc., one or a number of compounds of the invention of formula 5 are introduced, and / or the salts thereof, optionally together with a carrier, in an effective amount on the areas to be treated. The optional carrier used can be either liquid or solid and includes additives such as wetting agents, dispersants and other surfactants. The compounds of the formula (I) according to the invention can be included in preparations such as wettable powders, solutions, sprayable preparations, granules, emulsifiable concentrated preparations, etc. Examples of suitable solid carriers are natural and synthetic silicates and clays, carbon products and charcoal granules, natural and synthetic resins, waxes etc.
8001176 k8001176 k
Voorbeelden van geschikte vloeibare dragers zijn vater, aromatische koolwaterstoffen, alcoholen, plantaardige en minerale, oliën, ketonen enz.. De toe te passen hoeveelheid van de verbinding(en) volgens de uitvinding met formule 5, en/of een zout daarvan, in het 5 preparaat kan sterk variëren, doch zal in het algemeen tussen ongeveer 0,01 en ongeveer 90,0 gev.Ji liggen.Examples of suitable liquid carriers are vater, aromatic hydrocarbons, alcohols, vegetable and mineral, oils, ketones, etc. The amount of the compound (s) according to the invention of formula 5, and / or a salt thereof, to be used, in the The composition can vary widely, but will generally be between about 0.01 and about 90.0 percent by weight.
Zoals hierna zal worden aangetoond zijn de verbindingen volgens de uitvinding, alsmede de zouten daarvan, doeltreffend voor het bestrijden van vele verschillende insecten en mijten. De 1Q verbindingen volgens de uitvinding zijn bijvoorbeeld doeltreffende bestrijdingsmiddelen tegen muggen, vliegen, luizen, kalanders en mijten, zoals de spilt en teken. Afhankelijk van de speciale combinatie van de substituenten in formule 5, bezitten de verbindingen volgens de uitvinding een breed of betrekkelijk smal 15 spectrum met een buitengewoon hoge werkzaamheid tegen insecten en mijten. Van het ongedierte waartegen de verbindingen volgens de uitvinding doeltreffend zijn kan men noemen insecten van de klassen Lepidoptera, Orthoptera, Heteroptera, Homoptera, Diptera, Coleoptera en Hymenoptera en mijten van de Acarina klasse, waar-20 onder mijten van de Tetranychidae en Tarsonemidae familie en teken, zoals Ornithodoros.As will be shown below, the compounds of the invention, as well as their salts, are effective in controlling many different insects and mites. The 1Q compounds according to the invention are, for example, effective pesticides against mosquitoes, flies, lice, calenders and mites, such as the spindle and ticks. Depending on the special combination of the substituents in formula 5, the compounds of the invention have a broad or relatively narrow spectrum with extremely high activity against insects and mites. Among the pests against which the compounds according to the invention are effective one can mention insects of the classes Lepidoptera, Orthoptera, Heteroptera, Homoptera, Diptera, Coleoptera and Hymenoptera and mites of the Acarina class, including mites of the Tetranychidae and Tarsonemidae family and ticks, such as Ornithodoros.
Desgewenst kan men de verbindingen volgens de uitvinding tezamen met andere pesticiden, zoals carbamaten, fosfaten en regulatoren van de insectengroei, zoals bijvoorbeeld propoxur, 25 carbaryl, naled, dichlorvos, methoprene, kinoprene, hydroprene, cyhexatin resmethrin, fenvalerate, permethrin en fluvalivate, aanwenden.If desired, the compounds according to the invention can be used together with other pesticides, such as carbamates, phosphates and regulators of insect growth, such as, for example, propoxur, carbaryl, naled, dichlorvos, methoprene, kinoprene, hydroprene, cyhexatin resmethrin, fenvalerate, permethrin and fluvalivate. .
In de volgende voorbeelden betekent RT: kamertemperatuur. Voorbeeld IIn the following examples, RT means room temperature. Example I
30 Men voegde aan een geroerde oplossing van 0,2 g (0,99 m.mol) (6-fenoxy-2-pyridyl)methanol en 0,1U g (1,38 m.mol) triethylamine in ongeveer 15 ml diethylether in een stikstofatmosfeer en via een injectiespuit een oplossing van 1,5 m.mol van het zuurchloride van N-(2-chloor-^-trifluormethylfenylJvaline in diethylether toe. Daarna 35 roerde men het mengsel 30 minuten en beëindigde daarna de reactie met be- 800 1 1 76 # * 5 hulp van een verzadigde oplossing van natriumbicarbonaat in water. Vervolgens waste men de etherfase achtereenvolgens met een oplossing van natriumbicarbonaat in water, water en een oplossing van natriumchloride en filtreerde door siliciumdioxyde. Door afdes-5 tilleren van het oplosmiddel, gevolgd door dunne-laag-chromatogra-fie met behulp van een ronde chromatograaf en elueren met 20$ diethylether/hexaan verkreeg men de (6-fenoxy-2-pyridyl)methylester van N-(2-chloor-l*-trifluormethylfenyl) valine als een vrijwel kleurloze, viskeuze olie.To a stirred solution of 0.2 g (0.99 mole) (6-phenoxy-2-pyridyl) methanol and 0.1U g (1.38 mole) triethylamine in about 15 ml diethyl ether were added in nitrogen atmosphere and via a syringe a solution of 1.5 mole mol of the acid chloride of N- (2-chloro-trifluoromethylphenyl] valine in diethyl ether. Then the mixture was stirred for 30 minutes and then the reaction was quenched with 800 1 1 76 # * 5 aid of a saturated solution of sodium bicarbonate in water The ether phase was then washed successively with a solution of sodium bicarbonate in water, water and a solution of sodium chloride and filtered through silica, by distilling off the solvent, followed by thin layer chromatography on a round chromatograph and eluting with 20% diethyl ether / hexane, the (6-phenoxy-2-pyridyl) methyl ester of N- (2-chloro-1 * -trifluoromethylphenyl) valine was obtained as a virtually colorless, viscous oil.
1010
Voorbeeld IIExample II
A. Men voegde aan een oplossing van 0,37g (1,ö m.mol) 6-fenoxypyridy1-2-carboxaldehyde in 25 ml diethylether eerst 25 ml water en vervolgens 0,1^9g (3,0^ m.mol) natriumcyanide toe. Daarna 15 roerde men dit mengsel krachtig, terwijl men gedurende ongeveer 5 minuten hieraan een oplossing van 0,257g (2,1*7 m.mol) natrium-bisulfiet in 15 ml water toevoegde. Vervolgens roerde men het reactiemengsel nog 2 uren. Daarna scheidde men de organische fase af, waste haar met water, droogde haar boven calciumsulfaat 20 en destilleerde het oplosmiddel af, waardoor men cyaan (6-fenoxy- 2-pyridyl)methanol verkreeg.A. To a solution of 0.37g (1.10 mole) of 6-phenoxypyridy1-2-carboxaldehyde in 25 ml of diethyl ether was added first 25 ml of water and then 0.1 ^ 9g (3.0 ^ mole) sodium cyanide. This mixture was then stirred vigorously while adding a solution of 0.257g (2.1 * 7 moles) sodium bisulfite in 15 ml of water for about 5 minutes. The reaction mixture was then stirred for an additional 2 hours. The organic phase was then separated, washed with water, dried over calcium sulfate and the solvent was distilled off to obtain cyan (6-phenoxy-2-pyridyl) methanol.
B. Men voegde aan 2,5 m.mol van het zuurchloride van N-(2-fluor-l+-trifluormethyl)valine in diethylether eerst 1,3 ml triethylamine en daarna in ongeveer 2 minuten cyaan (6-fenoxy-2- 25 pyridyl)methanol in 5 ml diethylether, van deel A hiervoor, toe. Vervolgens roerde men het reactiemengsel ongeveer 18 uren en beëindigde daarna de reactie met behulp van een verzadigde oplossing van natriumbicarbonaat in water. Vervolgens waste men de organische fase achtereenvolgens met een oplossing van natriumbicarbonaat in 30 water, water en een oplossing van natriumchloride, droogde boven calciumsulfaat en destilleerde het oplosmiddel af. Door chromato-graferen van het verkregen, ruwe produkt met een ronde chromatograaf en elueren met 20$ diethylether/hexaan verkreeg men de cyaan(6-fenoxy-2-pyridyl)methylester van N-(2-fluor-H-trifluor-35 methylfenyl)valine als een lichtgele, viskeuze vloeistof.B. To 2.5 moles of the acid chloride of N- (2-fluoro-1 + -trifluoromethyl) valine in diethyl ether was first added 1.3 ml of triethylamine and then cyan (6-phenoxy-2- 25) in about 2 minutes pyridyl) methanol in 5 ml of diethyl ether, from part A above. The reaction mixture was then stirred for about 18 hours and then the reaction was terminated using a saturated aqueous sodium bicarbonate solution. The organic phase was then washed successively with a solution of sodium bicarbonate in water, water and a solution of sodium chloride, dried over calcium sulfate and the solvent was distilled off. Chromatographing the crude product obtained with a round chromatograph and eluting with 20% diethyl ether / hexane gave the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (2-fluoro-H-trifluoro-35 methylphenyl) valine as a pale yellow, viscous liquid.
800 1 1 76 6800 1 1 76 6
Voorbeeld IIIExample III
Men voegde aan een geroerde oplossing van MOmg (1,8 m.mol) cyaan (6-fenoxy-2-pyridyl)methanol, 590mg (2,0 m.mol) N-(2-chloor-U-trifluormethylfenyl)valine en 0,65 m.mol dimethyl-5 aminopyridine in 20 ml methyleenchloride en 2 ml dimethylformamide 2,0 m.mol NjN'-dicyclohexylcarbodiimide toe. Daarna roerde men dit reactiemengsel in een stikstofatmosfeer gedurende 2 uren, filtreerde het en extraheerde het met water. De waterfase werd geëxtraheerd met diethylether. Vervolgens waste men de samengevoegde organische 10 fasen met een verzadigde oplossing van natriumbicarbonaat in water, water en een verzadigde oplossing van natriumchloride in water, droogde boven calciumsulfaat en destilleerde het oplosmiddel af. Door chromatograferen van het verkregen ruwe produkt met een roterende chromatograaf onder elutie met 25/5T s diethylester/hexaan 15 verkreeg men de cyaan (6-fenoxy-2-pyridyl)methylester van N-(2-chloor-U-trifluormethylfenyl)valine als een kleurloze, viskeuze vloeistof.To a stirred solution of MOmg (1.8 mMol) cyano (6-phenoxy-2-pyridyl) methanol, 590mg (2.0 mMol) N- (2-chloro-U-trifluoromethylphenyl) valine and 0.65 mole mole dimethyl-5-aminopyridine in 20 ml methylene chloride and 2 ml dimethylformamide 2.0 mole mole NjN'-dicyclohexylcarbodiimide. This reaction mixture was then stirred in a nitrogen atmosphere for 2 hours, filtered and extracted with water. The water phase was extracted with diethyl ether. The combined organic phases were then washed with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution, dried over calcium sulfate and the solvent distilled off. Chromatography of the crude product obtained with a rotary chromatograph eluting with 25 / 5T diethyl ester / hexane gave the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (2-chloro-U-trifluoromethylphenyl) valine as a colorless, viscous liquid.
Op overeenkomstige wijze heeft men de cyaan (6-fenoxy-2-pyridyl)methylester van N-(2-chloor-^-difluormethoxyfenyl)-valine, 20 MS m/e 5Q0(M+), verkregen.Similarly, the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (2-chloro-1-difluoromethoxyphenyl) -valine, 20 MS m / e 5Q0 (M +), was obtained.
Voorbeeld IVExample IV
Men voegde aan een oplossing van 336 mg (1,32 m.mol) S-i^-chloorfenylJ-U-isopropyloxazolidine^^-dion en dimethyl-25 aminopyridine in 5 ml droge tetrahydrofuran een oplossing van 25^ mg (1,26 m.mol) (6-fenoxy-2-pyridyl)methanol in 3 ml droge tetrahydrofuran toe. Daarna roerde men dit mengsel ongeveer 20 uren in droge lucht, verdunde het met diethylether en waste het achtereenvolgens met een verzadigde oplossing van natriumbicarbonaat in 30 water, water en een verzadigde oplossing van natriumchloride in water. Na drogen boven calciumsulfaat destilleerde men het oplosmiddel af. Door chromatograferen van het verkregen, ruwe produkt, een gele vloeistof, met een roterende chromatograaf onder elutie met 15? diethylether/hexaan verkreeg men de (6-fenoxy-2-35 pyridyl)methylester van N-(^-chloorfenyl)valine als een kleurloze olie.To a solution of 336 mg (1.32 mole) of Si 2 -chlorophenyl] -U-isopropyloxazolidine dione and dimethyl-25-aminopyridine in 5 ml of dry tetrahydrofuran was added a solution of 25 mg (1.26 m. mol) (6-phenoxy-2-pyridyl) methanol in 3 ml dry tetrahydrofuran. This mixture was then stirred in dry air for about 20 hours, diluted with diethyl ether and washed successively with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution. After drying over calcium sulfate, the solvent was distilled off. By chromatography of the obtained crude product, a yellow liquid, with a rotary chromatograph eluting with 15? diethyl ether / hexane, the (6-phenoxy-2-35 pyridyl) methyl ester of N - (? - chlorophenyl) valine was obtained as a colorless oil.
800 1 1 76 c*- < 7800 1 1 76 c * - <7
Volgens de hiervoor beschreven werkwijze heeft men 3-(U-methylfenyl)-U-isopropyloxazolidine-2,5-dion met (6-fenoxy-2-pyridyl)methanol laten reageren tot de (6-fenoxy-2-pyridyl)-methyl-ester van N-(4-methylfenyl)valine.According to the method described above, 3- (U-methylphenyl) -U-isopropyloxazolidine-2,5-dione was reacted with (6-phenoxy-2-pyridyl) methanol to form the (6-phenoxy-2-pyridyl) -methyl ester of N- (4-methylphenyl) valine.
5 Op dezelfde wijze heeft men 3-(^-triiluormethylfenyl)- U-isopropyloxazolidine-2,5-dion met (6-fenoxy-2-pyridyl)methanol laten reageren tot de (6-fenoxy-2-pyridyl)methylester van N-(^-trifluormethylfenyl) valine.In the same manner, 3 - ((- - trifluoromethylphenyl) - U-isopropyloxazolidine-2,5-dione was reacted with (6-phenoxy-2-pyridyl) methanol to form the (6-phenoxy-2-pyridyl) methyl ester of N - (^ - trifluoromethylphenyl) valine.
10 Voorbeeld V10 Example V
Volgens de methode van voorbeeld III heeft men elk van de zuren N-(U-chloor-2-fluorfenyl)valine, N-(2-fluor-H-methylfenyl)-valine, N-(2,U-dichloorfenyl)valine, N-(U-trifluormethylfenyl) valine, N-(2-chloor-4-methylfenyl)valine en N-(4-di fluormethoxyf enyl) 15 valine met cyaan-(6-fenoxy-2-pyridyl)methanol laten reageren tot de respectievelijke esters: de cyaan(6-fenoxy-2-pyridyl)methylester van N-(U- chloor-2-fluorf enyl)valine, de cyaan(6-fenoxy-2-pyridyl)methylester van N-(2-fluor-20 U-methylf enyl)valine, de cyaan(6-fenoxy-2-pyridyl)methylester van N-(2,k- dichloorf enyl)valine, de cyaan(6-fenoxy-2-pyridyl)methylester van N-(U-tri- fluormethylfenyl)valine, 25 de cyaan(6-fenoxy-2-pyridyl)methylester van N-(2-chloor-According to the method of Example III, each of the acids has N- (U-chloro-2-fluorophenyl) valine, N- (2-fluoro-H-methylphenyl) -valine, N- (2, U-dichlorophenyl) valine, N- (U-trifluoromethylphenyl) valine, N- (2-chloro-4-methylphenyl) valine and N- (4-difluoromethoxyphenyl) valine react with cyano (6-phenoxy-2-pyridyl) methanol until the respective esters: the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (U-chloro-2-fluorophenyl) valine, the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (2-fluoro-) 20 U-methylphenyl) valine, the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (2, k-dichlorophenyl) valine, the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (U -trifluoromethylphenyl) valine, the cyan (6-phenoxy-2-pyridyl) methyl ester of N- (2-chloro-)
If-methylfenyl)valine en de cyaan(6-fenoxy-2-pyridyl)methylester van N-(h-di- fluormet hoxy f enyl valine.If-methylphenyl) valine and the cyano (6-phenoxy-2-pyridyl) methyl ester of N- (h-difluoromethoxyphenyl valine).
30 Voorbeeld VIExample VI
Men liet volgens de werkwijze van voorbeeld III N-(H-f luorf enyl)valine /2-(U-fluorfenylamino)-3-methylbutaanzuur7 reageren met cyaan(6-fenoxy-2-pyridyl)methanol tot de cyaan(6-fenoxy-2-pyridyl)methylester van N-(i+-fluorfenyl)valine /cyaan 35 (6-fenoxy-2-pyridyl)methyl 2-(k-fluorfenylamino)-3-methyl- butanoaat7· 800 1 1 76 8N- (Hf-fluorophenyl) valine / 2- (U-fluorophenylamino) -3-methylbutanoic acid 7 was reacted with cyano (6-phenoxy-2-pyridyl) methanol to give the cyano (6-phenoxy-2) according to the procedure of Example III. -pyridyl) methyl ester of N- (i + -fluorophenyl) valine / cyano 35 (6-phenoxy-2-pyridyl) methyl 2- (k-fluorophenylamino) -3-methyl-butanoate7,800 1 1 76 8
Op dezelfde wijze, onder toepassing van de werkwijze van voorbeeld III, heeft men elk van de zuren vermeld onder kolom I door reactie met cyaan(6-fenoxy-2-pyridylJmethanol omgezet in de esters opgesomd in kolom II. .Likewise, using the procedure of Example III, each of the acids listed under column I was converted into the esters listed in column II by reaction with cyano (6-phenoxy-2-pyridylmethanol).
5 I5 I
2- (l+-methylfenylamino)-3-methylbutaanzuur, 2- (it-chloorf enylamino)-3-methylbut aanzuur, 2-( it-methoxyfenylamino )-3-methylbutaanzuur, 2-( it-ethylfenylamino)-3-methylbut aanzuur2- (1 + -methylphenylamino) -3-methylbutanoic acid, 2- (it-chlorophenylamino) -3-methylbutanoic acid, 2- (it-methoxyphenylamino) -3-methylbutanoic acid, 2- (it-ethylphenylamino) -3-methylbutanoic acid
10 II10 II
cyaan( 6-fenoxy-2-pyridyl )methyl 2-(it-methylfenylamino) -3-methyl- butanoaat, cyaan(6-fenoxy-2-pyridyl)methyl 2-(lt-chloorfenylamino)-3-methylbut anoaat , 15 cyaan(6-fenoxy-2-pyridyl)methyl 2-(it-methoxyfenylamino)-3-methyl but anoaat en cyaan(6-fenoxy-2-pyridyl)methyl 2(it-ethylfenylamino)-3-methylbut anoaat.cyano (6-phenoxy-2-pyridyl) methyl 2- (it-methylphenylamino) -3-methyl-butanoate, cyano (6-phenoxy-2-pyridyl) methyl 2- (1-chlorophenylamino) -3-methylbutanoate, 15 cyano (6-phenoxy-2-pyridyl) methyl 2- (it-methoxyphenylamino) -3-methyl but anoate and cyano (6-phenoxy-2-pyridyl) methyl 2 (it-ethylphenylamino) -3-methylbutanoate.
20 Voorbeeld VIIExample VII
Men heeft volgens de werkwijze van voorbeeld I het zuur-chloride van 2-(2-chloor-lt-trifluormethylfenylamino)-3-methylbut aanzutu: met /6- (it-fluorfenoxy) -2-pyridy]^7methanol laten reageren tot /6- (it-fluorfenoxy) -2-pyridyl7methyl 2-(2-chloor-lt-trifluor-25 methylfenylamino)-3-methylbutanoaat, MS m/e it9ö (M+).The acid chloride of 2- (2-chloro-1-trifluoromethylphenylamino) -3-methylbut was reacted with / 6- (it-fluorophenoxy) -2-pyridyl] -7-methanol according to the procedure of Example I to give / 6- (it-fluoro-phenoxy) -2-pyridyl-7-methyl-2- (2-chloro-1-trifluoro-methyl-phenylamino) -3-methyl-butanoate, MS m / e it-9 (M +).
Voorbeeld VIIIExample VIII
Men voegde aan een mengsel van 2,63 m.mol 2-(2-chloor-lt-trifluormethylfenylamino)-3-methylbutaanzuur, 5 ml koude methyleen-30 chloride en 0,21 m.mol dimethylaminopyridine bij 0°C eerst 2,79 m.mol c< -methyl(6-fenoxy-2-pyridyl)methanol in 2 ml methyleen-chloride en daarna 2,61 m.mol dicyclohexylcarbodiimide toe. Daarna roerde men het verkregen reactiemengsel ongeveer lt uren bij kamertemperatuur en werkte het vervolgens op op de wijze als beschreven 35 in voorbeeld III. Door chromatograferen van het verkregen ruwe produkt op dunne—laag-chromatografieplaten onder elutie met 30?'s 800 1 1 76 9 diethylether/hexaan verkreeg men cC-methyl(6-fenoxy-2-pyridyl) methyl 2-(2-chloor-4-trifluormethylfenylami.no)-3-methylbutanoaat, MS m/e 492 (M+).A mixture of 2.63 moles mole of 2- (2-chloro-1-trifluoromethylphenylamino) -3-methylbutanoic acid, 5 ml of cold methylene chloride and 0.21 moles of dimethylaminopyridine at 0 ° C was first added to 2. Add 79 moles mole of methyl methyl (6-phenoxy-2-pyridyl) methanol in 2 ml of methylene chloride and then 2.61 moles of dicyclohexylcarbodiimide. The resulting reaction mixture was then stirred at room temperature for about 1 hour and then worked up as described in Example III. Chromatography of the crude product obtained on thin layer chromatography plates, eluting with 30% 800 1 1 76 9 diethyl ether / hexane, afforded cC-methyl (6-phenoxy-2-pyridyl) methyl 2- (2-chloro) 4-Trifluoromethylphenylamine) -3-methylbutanoate, MS m / e 492 (M +).
De alcohol, o£ -methyl(6-fenoxy-2-pyridyl)methanol werd 5 bereid door een Grignard-reactie van 6-fenoxypyridyl-2-carboxalde-hyde en methylmagnesiumbromide in tetrahydrofuran.The alcohol, £ -methyl (6-phenoxy-2-pyridyl) methanol, was prepared by a Grignard reaction of 6-phenoxypyridyl-2-carboxaldehyde and methyl magnesium bromide in tetrahydrofuran.
6-Fenoxypyridyl-2-carboxaldehyde werd bereid door oxyda-tie van 6-fenoxy-2-pyridylmethanol met chroomtrioxyde en pyridine in methyleenchloride.6-Phenoxypyridyl-2-carboxaldehyde was prepared by oxidation of 6-phenoxy-2-pyridylmethanol with chromium trioxide and pyridine in methylene chloride.
10 Onder toepassing van de werkwijze van dit voorbeeld heeft men eveneens 2-(2-chloor-4-trifluormethylfenylamino)-3-methylbutaanzuur met oC-methyl ZS-(4-fluorfenoxy)-2-pyridyl7 methanol laten reageren tot oC-methyl/S-(4-fluorfenoxy)-2-pyridyl7 methyl 2-(2-chloor-4-trifluormethylfenylamino)-3-methylbutanoaat.Using the procedure of this example, 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoic acid was also reacted with oC-methyl ZS- (4-fluorophenoxy) -2-pyridyl7 methanol to make oC-methyl / S- (4-fluorophenoxy) -2-pyridyl7 methyl 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoate.
15 Op overeenkomstige wijze heeft men door reactie van 2-(2-fluor-4-trifluormethylfenylamino)-3-methylbutaanzuur met oC -methyl(6-fenoxy-2-pyridyl)-methanol 0^-methyl(6-fenoxy-2-pyridyl)methyl 2-(2-fluor-4-trifluormethylfenylamino)-3-methylbutanoaat, MS m/e 476 (M+), verkregen.Likewise, by reaction of 2- (2-fluoro-4-trifluoromethylphenylamino) -3-methylbutanoic acid with oC -methyl (6-phenoxy-2-pyridyl) -methanol, O 2 -methyl (6-phenoxy-2- pyridyl) methyl 2- (2-fluoro-4-trifluoromethylphenylamino) -3-methylbutanoate, MS m / e 476 (M +).
2020
Voorbeeld IXExample IX
Volgens de werkwijze van voorbeeld VIII heeft men 2-(2-chloor-4-trifluormethylfenylamino)-3-methylbutaanzuur met oC -ethynyl(6-fenoxy-2-pyridyl)methanol laten reageren tot de 25 ester -ethynyl (6-fenoxy-2-pyridyl)methyl 2-(2-chloor-4- trifluormethylfenyl-amino)-3-methylbutanoaat, MS m/e 502 (M+).2- (2-Chloro-4-trifluoromethylphenylamino) -3-methylbutanoic acid was reacted with oC-ethynyl (6-phenoxy-2-pyridyl) methanol to give the ester -ethynyl (6-phenoxy-) 2-pyridyl) methyl 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoate, MS m / e 502 (M +).
De hiervoor genoemde alcohol werd verkregen door Grignard-reactie van 6-fenoxypyridyl-2-carboxaldehyde en ethynylmagnesium-bromide in tetrahydrofuran.The aforementioned alcohol was obtained by Grignard reaction of 6-phenoxypyridyl-2-carboxaldehyde and ethynylmagnesium bromide in tetrahydrofuran.
3030
Voorbeeld XExample X.
Men voegde aan 0,29g 2-(2-chloor-4-trifluormethylfenylamino )-3-methyl-butaanzuur in 10 ml benzeen bij kamertemperatuur 0,21g oxalylchloride en dimethylformamide toe. Na ongeveer 5 minu- 35 ten verwarmde men het mengsel tot ongeveer 40°C en stripte het oplosmiddel en de overmaat oxalylchloride af. Vervolgens voegde 800 1 1 76 10 men aan het zuurchloride in tetrahydrofuran onder roeren 0,2g (6-fenoxy-2-pyridyl)-methylthiol en 0,22g dimethylaminopyridine toe. Daarna roerde men het reactiemengsel ongeveer 18 uren, werkte het op met diethylether, waste het met water en een oplossing van 5 natriumchloride en droogde boven natriumsulfaat. Door chromatogra- feren van het verkregen reactieprodukt op platen onder toepassing van 20$'s ethylacetaat/hexaan verkreeg men de S-(6-fenoxy-2-pyridyl) methylthiolester van 2-(2-chloor-l+-trifluormethylfenylamino)-3-methylbutaanzuur, MS m/e U9U (M+), formule 5» W = zwavel, Y = 10 chloor, t = een, Z - trifluormethyl en R^Rg^Rj. is waterstof.0.21 g of oxalyl chloride and dimethylformamide were added to 0.29 g of 2- (2-chloro-4-trifluoromethylphenylamino) -3-methyl-butanoic acid in 10 ml of benzene at room temperature. After about 5 minutes, the mixture was heated to about 40 ° C and the solvent and excess oxalyl chloride stripped off. Then 800 g of 1 76 ml were added to the acid chloride in tetrahydrofuran with stirring 0.2 g (6-phenoxy-2-pyridyl) methylthiol and 0.22 g dimethylaminopyridine. The reaction mixture was then stirred for about 18 hours, worked up with diethyl ether, washed with water and a solution of sodium chloride and dried over sodium sulfate. Chromatography of the reaction product obtained on plates using 20% ethyl acetate / hexane gave the S- (6-phenoxy-2-pyridyl) methylthiol ester of 2- (2-chloro-1 + -trifluoromethylphenylamino) -3- methyl butanoic acid, MS m / e U9U (M +), formula 5 »W = sulfur, Y = 10 chlorine, t = one, Z - trifluoromethyl and R 1 Rg ^ Rj. is hydrogen.
Op overeenkomstige wijze heeft men de S-(6-fenoxy-2-pyridyl)-methylthiolester van 2-(2-fluor-U-trifluormethylfenylamino )-3-methylbutaanzuur, MS m/e (M+), verkregen.The S- (6-phenoxy-2-pyridyl) -methylthiol ester of 2- (2-fluoro-U-trifluoromethylphenylamino) -3-methylbutanoic acid, MS m / e (M +), was obtained in a corresponding manner.
15 Voorbeeld XIExample XI
A. Men voegde aan een tot ongeveer 5°C gekoelde oplossing van 3,38 m.mol. 2-(2-chloor-lt-tri fluormethylfenylamino )-3-methyl-diaethylformamide butaanzuur in 25 ml*3,38 m.mol triethylamine en 3,38 m.mol ethyl-chloorformiaat toe. Daarna roerde men het reactiemengsel gedurende 20 ongeveer 15 minuten en voegde 6,76 m.mol natriumwaterstofsulfide en 10 ml dimethylformamide toe. Vervolgens roerde men het reactiemengsel ongeveer 1,5 uren bij 5°C. Daarna werd het reactiemengsel opgewerkt door toevoegen van diethylether en aanzuren met 5%'s zwavelzuur. Men waste de etherlaag met water en een oplossing van 25 natriumchloride, droogde boven natriumsulfaat en destilleerde het oplosmiddel af, waardoor men het thiozuur van 2-(2-chloor-l+-trifluormethylfenylamino)-3-methylbutaanzuur verkreeg.A. It was added to a solution of 3.38 mMol cooled to about 5 ° C. 2- (2-Chloro-1-trifluoromethylphenylamino) -3-methyl-diaethylformamide butanoic acid in 25 ml. * 3.38 mole triethylamine and 3.38 mole ethyl chloroformate. The reaction mixture was then stirred for about 15 minutes and 6.76 moles of sodium hydrogen sulfide and 10 ml of dimethylformamide were added. The reaction mixture was then stirred at 5 ° C for about 1.5 hours. The reaction mixture was then worked up by adding diethyl ether and acidifying with 5% sulfuric acid. The ether layer was washed with water and a solution of sodium chloride, dried over sodium sulfate and the solvent was distilled off to obtain the thioic acid of 2- (2-chloro-1 + -trifluoromethylphenylamino) -3-methylbutanoic acid.
B. Men voegde aan 15 ml dimethylformamide en 10 ml tetrahydrofuran 1,60 m.mol van het thiozuur van deel A, U,01 m.mol 30 ΚΗΟΟ^ en 1,60 m.mol van het mesylaat van -cyaan-(6-fenoxy-2- pyridyl)methanol toe. Daarna roerde men dit reactiemengsel ongeveer 18 uren bij kamertemperatuur. Vervolgens nam men het reactiemengsel op in diethylether, waste het met water en een oplossing van natriumchloride, droogde het boven natriumsulfaat en stripte 35 het oplosmiddel af, waardoor men de S- o( -cyaan-(6-fenoxy-2- pyridyl)-methylthioester van 2-(2-chloor-i+-trifluormethylfenyl- 800 1 1 76 11 amino)-3-methylbutaanzuur verkreeg.B. To 15 ml of dimethylformamide and 10 ml of tetrahydrofuran were added 1.60 mole mol of the thioic acid of part A, U, 01 mole mol 30 µm and 1.60 mole mol of the cyyl mesylate (6 phenoxy-2-pyridyl) methanol. This reaction mixture was then stirred at room temperature for about 18 hours. The reaction mixture was then taken up in diethyl ether, washed with water and a solution of sodium chloride, dried over sodium sulfate and stripped of the solvent to give the S- (cyano- (6-phenoxy-2-pyridyl) -) methyl thioester of 2- (2-chloro-1 + -trifluoromethylphenyl-800 1 1 76 11 amino) -3-methylbutanoic acid.
Op overeenkomstige wijze heeft men de S-oC -methyl-(6-fenoxy-2-pyridyl)methylthioester van 2-(2-chloor-U-trifluor-methylfenylamino)-3-methylbutaanzuur4MS m/e 508 (M+) en de S-5 oC-methyl-(6-fenoxy-2-pyridyl)methylthioester van 2- (2-fluor-1*-trifluormethylfenylamino)-3-methylbutaanzuur, MS m/e k92 (M+), verkregen.Similarly, the S-oC-methyl- (6-phenoxy-2-pyridyl) methylthioester of 2- (2-chloro-U-trifluoro-methylphenylamino) -3-methylbutanoic acid 4MS m / e 508 (M +) and the S -5 ° C-methyl- (6-phenoxy-2-pyridyl) methylthioester of 2- (2-fluoro-1 * -trifluoromethylphenylamino) -3-methylbutanoic acid, MS m / e k92 (M +).
Men behandelde twee groepen van 10 telkens 0-2k uren oude Heliothis vires censTu? de derde fase van de ontwikkeling met 10 1 /ul van (6-fenoxy-2-pyridyl)methyl 2-(2-chloor-U~trifluormethyl- fenoxy-2-pyridyl)methyl 2- (2-chloor-l*-trifluormethylfenylamino)-3-methylbutanoaat in aceton in vijf verschillende concentraties door dit middel aan de rugzijde van de thorax toe te dienen. Twee groepen van elk 10 werden op overeenkomstige wijze met alleen 15 1/il aceton als controle behandeld. Men hield de larven afzonderlijk 72 uren bij 25°C en 16 uren belichten in kunststofbekers van 30 ml waarin een kunstmatig medium was aangebracht. Na 72 uren berekende men het aantal dode larven als percentage van het totale aantal dat aanvankelijk was behandeld en corrigeerde dit percen-20 tage op eventuele mortaliteit in de controlegroepen volgens de formule van Abbott. De LD<-Q van de verbinding was minder dan 0,05*.Two groups of 10 were each treated 0-2k hours old Heliothis vires censTu? the third stage of the development with 10 µl of (6-phenoxy-2-pyridyl) methyl 2- (2-chloro-trifluoromethyl-phenoxy-2-pyridyl) methyl 2- (2-chloro-1 * - trifluoromethylphenylamino) -3-methylbutanoate in acetone in five different concentrations by administering this agent on the back of the thorax. Two groups of 10 each were similarly treated with 15 µl acetone alone as a control. The larvae were kept separately for 72 hours at 25 ° C and exposed for 16 hours in 30 ml plastic beakers in which an artificial medium was applied. After 72 hours, the number of dead larvae was calculated as a percentage of the total number initially treated and this percentage corrected for any mortality in the control groups according to Abbott's formula. The LD <-Q of the compound was less than 0.05 *.
800 1 1 76800 1 1 76
Claims (11)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1677579A | 1979-03-02 | 1979-03-02 | |
| US1677579 | 1979-03-02 | ||
| US06/069,445 US4226872A (en) | 1979-08-24 | 1979-08-24 | Pyridyl esters of α-substituted amino acids |
| US6944579 | 1979-08-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8001176A true NL8001176A (en) | 1980-09-04 |
Family
ID=26689048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8001176A NL8001176A (en) | 1979-03-02 | 1980-02-27 | PYRIDYL ESTERS AND THIO-ESTERS OF AMINO ACIDS, INTERIM PRODUCTS FOR THE SAME AND METHODS FOR PREPARING AND USING THESE COMPOUNDS. |
Country Status (9)
| Country | Link |
|---|---|
| AR (1) | AR226301A1 (en) |
| AU (1) | AU531723B2 (en) |
| CH (1) | CH644846A5 (en) |
| DE (1) | DE3005201A1 (en) |
| FR (2) | FR2450254A1 (en) |
| GB (1) | GB2046247B (en) |
| IL (1) | IL59385A (en) |
| IT (1) | IT8020045A0 (en) |
| NL (1) | NL8001176A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3005201A1 (en) * | 1979-03-02 | 1980-09-11 | Zoecon Corp | NEW ESTERS AND THIOLESTERS OF N-PHENYL-SUBSTITUTED VALINE DERIVATIVES |
| EP0145661A3 (en) * | 1983-12-02 | 1986-03-19 | Ciba-Geigy Ag | Alcohols |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4163787A (en) * | 1977-03-14 | 1979-08-07 | The Dow Chemical Company | Substituted pyridine methyl esters of cyclopropane carboxylic acids and their use as insecticides |
| GB1588111A (en) * | 1977-03-21 | 1981-04-15 | Zoecon Corp | Esters and thiolesters of amino acids intermediates therefor processes for their production and compositions including them |
| DE2861000D1 (en) * | 1977-07-20 | 1981-11-26 | Ciba Geigy Ag | Phenyl acetates of 2-oxypyridyl, process for their preparation and their use as pesticides |
| JPS5579368A (en) * | 1978-12-11 | 1980-06-14 | Nissan Chem Ind Ltd | Phenylcyclopropanecarboxylic acid derivative, its preparation, and insecticide and acaricide |
| DE3005201A1 (en) * | 1979-03-02 | 1980-09-11 | Zoecon Corp | NEW ESTERS AND THIOLESTERS OF N-PHENYL-SUBSTITUTED VALINE DERIVATIVES |
-
1980
- 1980-02-12 DE DE19803005201 patent/DE3005201A1/en not_active Withdrawn
- 1980-02-14 IL IL59385A patent/IL59385A/en unknown
- 1980-02-18 GB GB8005424A patent/GB2046247B/en not_active Expired
- 1980-02-20 IT IT8020045A patent/IT8020045A0/en unknown
- 1980-02-27 AR AR280110A patent/AR226301A1/en active
- 1980-02-27 NL NL8001176A patent/NL8001176A/en not_active Application Discontinuation
- 1980-02-28 FR FR8004483A patent/FR2450254A1/en active Granted
- 1980-02-29 AU AU56028/80A patent/AU531723B2/en not_active Ceased
- 1980-02-29 CH CH163980A patent/CH644846A5/en not_active IP Right Cessation
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1983
- 1983-03-23 FR FR8304764A patent/FR2521138A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AR226301A1 (en) | 1982-06-30 |
| FR2450254B1 (en) | 1984-02-24 |
| IT8020045A0 (en) | 1980-02-20 |
| GB2046247A (en) | 1980-11-12 |
| CH644846A5 (en) | 1984-08-31 |
| IL59385A0 (en) | 1980-05-30 |
| IL59385A (en) | 1983-11-30 |
| AU5602880A (en) | 1980-09-04 |
| FR2521138A1 (en) | 1983-08-12 |
| FR2450254A1 (en) | 1980-09-26 |
| GB2046247B (en) | 1983-03-30 |
| AU531723B2 (en) | 1983-09-01 |
| DE3005201A1 (en) | 1980-09-11 |
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