MXPA97008891A - N-piperidins (substitute arilmetil) -4- (bis (substitute fenil or piridil) methyl) insectici - Google Patents
N-piperidins (substitute arilmetil) -4- (bis (substitute fenil or piridil) methyl) insecticiInfo
- Publication number
- MXPA97008891A MXPA97008891A MXPA/A/1997/008891A MX9708891A MXPA97008891A MX PA97008891 A MXPA97008891 A MX PA97008891A MX 9708891 A MX9708891 A MX 9708891A MX PA97008891 A MXPA97008891 A MX PA97008891A
- Authority
- MX
- Mexico
- Prior art keywords
- bis
- compound according
- methyl
- grams
- piperidine
- Prior art date
Links
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title claims abstract description 14
- WGNUNYPERJMVRM-UHFFFAOYSA-N 3-pyridylacetic acid Chemical compound OC(=O)CC1=CC=CN=C1 WGNUNYPERJMVRM-UHFFFAOYSA-N 0.000 title description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical group 0.000 claims abstract description 12
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 7
- 229910052720 vanadium Inorganic materials 0.000 claims abstract description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 6
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 4
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims abstract description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- -1 cyano, aminocarbonyl Chemical group 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 49
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 41
- 241000238631 Hexapoda Species 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 2
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 2
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 1
- XGVWUTHPRSDCGD-UHFFFAOYSA-N [1-[(4-pyridin-2-yloxyphenyl)methyl]piperidin-4-yl]-bis[4-(trifluoromethyl)phenyl]methanol Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C=1C=CC(=CC=1)C(F)(F)F)(O)C(CC1)CCN1CC(C=C1)=CC=C1OC1=CC=CC=N1 XGVWUTHPRSDCGD-UHFFFAOYSA-N 0.000 claims 1
- QBZLONOZPJUPBM-UHFFFAOYSA-N [1-[(4-pyridin-2-ylphenyl)methyl]piperidin-4-yl]-bis[4-(trifluoromethyl)phenyl]methanol Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C=1C=CC(=CC=1)C(F)(F)F)(O)C(CC1)CCN1CC(C=C1)=CC=C1C1=CC=CC=N1 QBZLONOZPJUPBM-UHFFFAOYSA-N 0.000 claims 1
- AONOIZJWDLQVOR-UHFFFAOYSA-N [1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-yl]-bis[4-(trifluoromethyl)phenyl]methanol Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C=1C=CC(=CC=1)C(F)(F)F)(O)C(CC1)CCN1CC(C=C1)=CC=C1OC1=NC=CC=N1 AONOIZJWDLQVOR-UHFFFAOYSA-N 0.000 claims 1
- OSFHLWVQRKIIKM-UHFFFAOYSA-N [1-[[4-(2-ethyltetrazol-5-yl)phenyl]methyl]piperidin-4-yl]-bis[4-(trifluoromethyl)phenyl]methanol Chemical compound CCN1N=NC(C=2C=CC(CN3CCC(CC3)C(O)(C=3C=CC(=CC=3)C(F)(F)F)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 OSFHLWVQRKIIKM-UHFFFAOYSA-N 0.000 claims 1
- CUJNHIPIMVQOGF-UHFFFAOYSA-N [1-[[4-(2-methyltetrazol-5-yl)phenyl]methyl]piperidin-4-yl]-bis[4-(trifluoromethyl)phenyl]methanol Chemical compound CN1N=NC(C=2C=CC(CN3CCC(CC3)C(O)(C=3C=CC(=CC=3)C(F)(F)F)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 CUJNHIPIMVQOGF-UHFFFAOYSA-N 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 239000002917 insecticide Substances 0.000 abstract description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical group [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 42
- 239000000243 solution Substances 0.000 description 36
- 238000012360 testing method Methods 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 33
- 238000003786 synthesis reaction Methods 0.000 description 33
- 239000007787 solid Substances 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000007864 aqueous solution Substances 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 230000000749 insecticidal effect Effects 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 235000005911 diet Nutrition 0.000 description 10
- 230000037213 diet Effects 0.000 description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 229910052749 magnesium Inorganic materials 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 241000256244 Heliothis virescens Species 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 150000004820 halides Chemical class 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- SEAOBYFQWJFORM-UHFFFAOYSA-N 1-bromo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(Br)C=C1 SEAOBYFQWJFORM-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000002270 dispersing agent Substances 0.000 description 6
- 239000004495 emulsifiable concentrate Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 244000045195 Cicer arietinum Species 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 description 5
- IFNYKKVGUPRJDA-UHFFFAOYSA-N [1-[(4-propoxyphenyl)methyl]piperidin-4-yl]-bis[2-(trifluoromethyl)phenyl]methanol Chemical compound C1=CC(OCCC)=CC=C1CN1CCC(C(O)(C=2C(=CC=CC=2)C(F)(F)F)C=2C(=CC=CC=2)C(F)(F)F)CC1 IFNYKKVGUPRJDA-UHFFFAOYSA-N 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- CPPOGPUWURTIKD-UHFFFAOYSA-N piperidin-4-yl-bis[4-(trifluoromethoxy)phenyl]methanol Chemical compound C=1C=C(OC(F)(F)F)C=CC=1C(C=1C=CC(OC(F)(F)F)=CC=1)(O)C1CCNCC1 CPPOGPUWURTIKD-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 240000007124 Brassica oleracea Species 0.000 description 4
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 4
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 4
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- XFJYCXYUEHJPTD-UHFFFAOYSA-N [1-[[4-(2-methyltetrazol-5-yl)phenyl]methyl]piperidin-4-yl]-bis[4-(trifluoromethoxy)phenyl]methanol Chemical compound CN1N=NC(C=2C=CC(CN3CCC(CC3)C(O)(C=3C=CC(OC(F)(F)F)=CC=3)C=3C=CC(OC(F)(F)F)=CC=3)=CC=2)=N1 XFJYCXYUEHJPTD-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- 230000017066 negative regulation of growth Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- NUBFWKKIXMLXAF-UHFFFAOYSA-N (1-benzylpiperidin-4-yl)-bis[4-(trifluoromethoxy)phenyl]methanol Chemical compound C=1C=C(OC(F)(F)F)C=CC=1C(C=1C=CC(OC(F)(F)F)=CC=1)(O)C(CC1)CCN1CC1=CC=CC=C1 NUBFWKKIXMLXAF-UHFFFAOYSA-N 0.000 description 3
- IGYQMYPWCOXXRI-UHFFFAOYSA-N (1-benzylpiperidin-4-yl)-bis[4-(trifluoromethoxy)phenyl]methanol;hydrochloride Chemical compound Cl.C=1C=C(OC(F)(F)F)C=CC=1C(C=1C=CC(OC(F)(F)F)=CC=1)(O)C(CC1)CCN1CC1=CC=CC=C1 IGYQMYPWCOXXRI-UHFFFAOYSA-N 0.000 description 3
- KTRYYFCAVWLDRN-UHFFFAOYSA-N (2-ethyl-1,3-benzoxazol-5-yl)methanol Chemical compound OCC1=CC=C2OC(CC)=NC2=C1 KTRYYFCAVWLDRN-UHFFFAOYSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- XRBXPIMJKHVDAZ-UHFFFAOYSA-N 2-methyl-4-(4-methylphenyl)-1,2,4-triazol-3-one Chemical compound C1=CC(C)=CC=C1N1C(=O)N(C)N=C1 XRBXPIMJKHVDAZ-UHFFFAOYSA-N 0.000 description 3
- WHIFEKRDYLWPBO-UHFFFAOYSA-N 4-(2-methyltetrazol-5-yl)benzaldehyde Chemical compound CN1N=NC(C=2C=CC(C=O)=CC=2)=N1 WHIFEKRDYLWPBO-UHFFFAOYSA-N 0.000 description 3
- 235000016068 Berberis vulgaris Nutrition 0.000 description 3
- 241000335053 Beta vulgaris Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-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
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- NWOUTWBXYWCULM-UHFFFAOYSA-N [2-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]methanol Chemical compound FC(OC1=CC=C(C=C1)C1N(CCCC1)CO)(F)F NWOUTWBXYWCULM-UHFFFAOYSA-N 0.000 description 3
- HUKHPQDHDJJCFK-UHFFFAOYSA-N [4-(2-methyltetrazol-5-yl)phenyl]methanol Chemical compound CN1N=NC(C=2C=CC(CO)=CC=2)=N1 HUKHPQDHDJJCFK-UHFFFAOYSA-N 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- VWLICBPRIGYGMT-UHFFFAOYSA-N ethyl 1-[(2-ethyl-1,3-benzoxazol-5-yl)methyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1CC1=CC=C(OC(CC)=N2)C2=C1 VWLICBPRIGYGMT-UHFFFAOYSA-N 0.000 description 3
- NKNJKFOIJYBVKB-UHFFFAOYSA-N ethyl 1-[2-(4-methoxyphenyl)ethyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1CCC1=CC=C(OC)C=C1 NKNJKFOIJYBVKB-UHFFFAOYSA-N 0.000 description 3
- WTHNCYHQTJXAEL-UHFFFAOYSA-N ethyl 1-trimethylsilylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN([Si](C)(C)C)CC1 WTHNCYHQTJXAEL-UHFFFAOYSA-N 0.000 description 3
- PWYYLVBUFQGBPR-UHFFFAOYSA-N ethyl 2-ethyl-1,3-benzoxazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2OC(CC)=NC2=C1 PWYYLVBUFQGBPR-UHFFFAOYSA-N 0.000 description 3
- FBHJNBWUGONVNS-UHFFFAOYSA-N ethyl 4-hydroxy-3-nitrobenzoate Chemical compound CCOC(=O)C1=CC=C(O)C([N+]([O-])=O)=C1 FBHJNBWUGONVNS-UHFFFAOYSA-N 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
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- FSDMUCPKRVKUCG-UHFFFAOYSA-N piperidin-4-yl-bis[2-(trifluoromethoxy)phenyl]methanol Chemical compound C=1C=CC=C(OC(F)(F)F)C=1C(C=1C(=CC=CC=1)OC(F)(F)F)(O)C1CCNCC1 FSDMUCPKRVKUCG-UHFFFAOYSA-N 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920005552 sodium lignosulfonate Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000006387 trifluoromethyl pyridyl group Chemical group 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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Abstract
The compounds of structure (1), the corresponding N-oxides and the agriculturally acceptable salts are described as effective insecticides. In said formula, U is - (CH2) n, Q is hydroxy, R is formula (11), in which, V, W, Y, Z are each hydrogen, X is a 5-6 membered heterocycle; optionally substituted with halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, or aminocarbonyl, and the heterocycle is optionally connected to the phenyl ring via a -O-, -S-, - (CH2) p, - C (O) -, or -O- (CR3R4) q; R1 and R2 are independently selected from phenyl or pyridyl substituted with haloalakyl or haloalkoxy; R3 and R4 is independently selected from hydrogen and methyl, n and p are independently 1, 2, or 3,; and q is 1 or 2, with the proviso that at least one of R1 and R2 is substituted in the para position, no more than two of R3 and R4 are methyl, each aliphatic portion contains no more than 4 carbon atoms; Halogen means bromide, chloride or fluoride, each heterocycle contains 1 to 4 carbon atoms, or 1 or 2 oxygen atoms of sulfur, or 1 or 2 atoms of nitrogen. trogen and a sulfur oxygen atom
Description
N-IARILMETIL PIPERIPINES SUBSTITUTE) -4-rBIS (FEIMIL OR PIRIDIL SUBSTITU.PAS iMETIU INSECTICIDES
DESCRIPTION OF THE INVENTION
The present invention relates to methods for insect control. In particular, it refers to the control by the application of certain novel N- (arylmethyl substituted) -4- [bis (phenyl or pyridyl substituted) methyl piperidines to the site where insect control is needed. It has now been found that the compounds of the following structure and their corresponding N-oxides, as well as their agriculturally acceptable salts, are active as insecticides:
wherein: U is - (CH2) p; Q is hydroxy; R is
wherein, V, W, Y, Z are each hydrogen;
X is a 5-6 membered heterocycle; optionally substituted with halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, haloalkoxyalkyl, or aminocarbonyl; and the heterocycle is optionally connected to the phenyl ring through a ligation -O-, -S-, - (CH2) P, -C (O) -, or -O- (CR3R4) q; R1 and R2 are independently selected from phenyl or pyridyl substituted with haloalkyl or haloalkoxy; R3 and R4 are independently selected from hydrogen and methyl; n and p are independently 1, 2, or 3; and q is 1 or 2; with the proviso that at least one of R1 and R2 is substituted in the para position of the phenyl ring or the 5 position of a 2-pyridyl ring; no more than two of R3 and R4 are methyl; each aliphatic portion contains no more than 4 carbon atoms; halogen means bromide, chloride or fluoride; each heterocycle contains from 1 to 4 carbon atoms, or 1 or 2 oxygen or sulfur atoms, or 1 or 2 nitrogen atoms and an oxygen or sulfur atom; and the corresponding N-oxides the agriculturally acceptable salts. Preferred are those compounds in which in X the heterocycle is selected from 1, 2, 4-oxadiazolyl, oxazolinyl, pyridazinyl, pyrazinyl, pyrazolyl, pyridyl, pyrimidyl, pyrolyl, 2H-tetrazol-5-yl, 1, 2,3 -thiadiazolyl, 1,3,5-triazinyl, and 1,4-triazolyl, optionally substituted halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, or haloalkoxyalkyl, and the optional ligation is selected from -O-, - (CH2) P, or -O- (CHR3) q; R1 and R2 are independently selected from trifluoromethyl-phenyl, trifluoromethoxyphenyl, trifluoromethylpyridyl and trifluoromethoxy-pyridyl; n 2s 1, and p and q are independently 1 or 2; as long as halogen means chlorine or fluoro; and the corresponding N-oxides and the agriculturally acceptable salts. Particularly preferred are those compounds in which X is a heterocycle selected from 1,4-oxadiazol-5-yl, oxazolin-2-yl, pyrazol-3-yl, pyrid-2-yl, pyrimidin-2-yl. , pyrol-2-yl, pyrol-3-yl, 2H-tetrazol-5-yl, 1, 2,3-thiadiazol-4-yl, 1, 2,4-triazol-3-yl, optionally substituted with halogen, cyano, alkyl, haloalkyl, or alkoxyalkyl, and the optional ligation is selected from -O-, -O-CH2-, or -O-CH (CH3); R1 and R2 are independently selected from p-trifluoromethoxy phenyl, p-trifluoromethylphenyl, 5-trifluoromethylpyrid-2-yl, and 5-trifluoro-methoxypyrid-2-yl; and the corresponding N-oxides and the agriculturally acceptable salts. The N-oxides include the N-oxides of piperidine, the N-oxides of pyridine, or both. The compounds of the present invention are prepared by methods generally known to those skilled in the art. In the method in Scheme 1, where R1 and R2 are the same, ethyl piperidin-4-ylcarboxylate was reacted with either appropriately substituted alkyl halide, for example, 4-methoxyphenylmethyl bromide, or with an appropriately substituted aldehyde. under reductive conditions, for example, 4-phenoxy-benzaldehyde, providing the ethyl carboxylate N-alkylpiperodin-4-yl-substituted (A). The intermediate (A) was then treated with more than two molar equivalents of the Grignard reagent of an appropriately substituted halide, for example, 4-trifluoromethoxy phenyl magnesium bromide., yielding the N- (substituted alkyl) -4- [bis-hydroxymethyl (substituted) methyl] (I) piperidine, for example, N- (4-methoxyphenyl-methyl) -4- [bis (4-trifluoromethoxy-phenyl) -hydroxymethyl) ] pipe ridine (Compound 1). Example 1 provides a detailed description of how these reactions are conducted. Another method, again for cases where R1 and R2 are the same, is shown in Scheme 2. In this method, ethyl piperidin-4-ylcarboxylate was reacted with diethyl carbamoyl chloride, under basic conditions, providing the corresponding intermediate Ethyl N-diethylaminocarbonylpiperidin-4-yl carboxylate (B). The intermediate (BJ was treated with more than two molar equivalents of the appropriately substituted halide Grignard reagent, yielding the piperidine N-diethylaminocarbonyl-4- [bis (phenyl or substituted pyridyl) methyl] (C) The intermediate (C) after is treated with lithium aluminum hydride, providing the piperidine 4- [bis (phenyl or substituted pyridyl) hydroxymethyl] (JJJ, for example 4- [bis (4-trifluoromeoxyphenyl) hydroxymethyl] piperidine, as presented in Scheme 2a, the intermediate (Mj can be reacted with either an appropriately substituted alkyl halide or with an appropriately substituted aldehyde, as previously described, providing the N- (substituted alkyl) -4- [bis (phenyl or substituted pyridyl) hydroxymethyl] piperidine] ([), for example, N- [4- (2-methyltetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine (Compound 9) For the preparation of those compounds wherein R 1 and R2 can be pyridyl, pyridyl bromide or appropriate is lithiated at 78 ° C with tert-butyllithium, and the resulting product was used as described for magnesium Grignard reagents. The preparation of the intermediate (HJ, using the method described above, provided relatively low (M.) yields.) In a preferred method for preparing the intermediary of piperidine 4- [bis (substituted phenyl) hydroxymethyl] (H.), reacting ethyl piperidin-4-ylcarboxylate with chlorotrimethylsilane under basic conditions in diethyl ether, affording ethyl N- (trimethylsilyl) piperidin-4-yl-carboxylate The thus prepared ethyl carboxylate was then reacted with more than two equivalents of the reactant Grignard of an appropriately substituted halide, a previously described method, providing in intermediary (MJ) Both steps of this method provided the product in a good yield.Example 3 provides a detailed description of how this reaction is conducted. The intermediary piperidine 4- [bis (phenyl or substituted pyridyl) -hydroxymethyl] (MJ described above, can also react, com or is shown in Scheme 2a, with an appropriately substituted acid chloride, for example, 4- (1-methyl-tetrazol-5-yl) benzoyl chloride, under basic conditions, yielding the N- (carbonyl substituted) piperidine. [bis- (phenyl or substituted pyridyl) -hydroxymethyl] corresponding (GJ. The intermediate (G) is reduced with the borane-methyl sulfide complex, providing the N- (substituted alkyl) -4- [bis (hydroxymethyl) substituted] piperidine (I), for example, N- [4- (1 -methyltetrazol-5-yl) -phenylmethyl] -4- [bis (4-trifluoromethoxyphenyl) -hydroxymethyl] piperidine (Compound 8). Scheme 4 shows the method used when R1 and R2 are not equal. Here, 4-aminocarbonylpiperidine was reacted with an appropriately substituted alkyl halide, for example, 4- (1,3-dioxolan-2-yl) phenylmethyl chloride, under basic conditions, providing the piperidine N- (substituted alkyl) - 4-amino-carbonyl (). Treatment of the intermediate (H) with phosphorous oxychloride yields the corresponding N- (alkyl substituted) -4-cyanocarbonyl piperidine (JJ, which in turn is reacted with the Grignard reagent of an appropriately substituted halide, for example, bromide of 2-trifluoromethoxyphenyl magnesium, yielding the corresponding N- (substituted alkyl) -4- (carbonyl substituted) piperidine (K) The intermediate (KJ was reacted with a Grignard reagent different from an appropriately substituted halide, for example, 4-trifluoromethoxyphenyl magnesium bromide, yielding the N- (alkyl substituted) -4- [di (substituted phenyl) hydroxymethyl] () piperidine, for example, N- [4- (1,3-dioxolan-2 -yl) phenylmethyl] -4 - [(4-trifluoromethoxyphenyl) (2-trifluoromethoxyphenyl) hydroxymethyl] piperidine (Compound 103). In an alternative step route, the dehydroxy compounds (IB.) Are also prepared by reducing N- (alkyl substituted) -4- [bis (phenyl or pyridyl substituted) -hydroxymethyl] () piperidines with trifluoroacetic acid and triethyl. Isilane in methylene chloride.
SCHEME 1
n «1-3 (C2Hs) (i-Pr) 2N / Nal« halogen (Br, Cl)?
CaHsOH
> 2 moles of an intermediate containing halide, e.g.
J? SCHEME 2
fi
> 2 moles of an intermediate containing halide v.gr.,
Mg / (C2H5) 20 / BrCHaCHjBr where R1 «R2«
11 SCHEME 2A
- (CH2) n-X (C2Hs) (i-Pr) 2N / Nal
J? SCHEME 3
(C2HS) 20 M
> 2 moles of an intermediate containing halide, e.g.
where R '- R2 «IJL, ^ OCF3
SCHEME 4
- X = h
R1-MgBr
1? Included within the scope of the present invention are the N-oxides (JAJ) of the compounds prepared through the methods described above.The N-oxides (LA) were prepared by treating the parent compounds, for example, N- [4 ( 2-methyl-2H-tetrzol-5-yl) phenylmethyl] -4-] bis (4-trifluoromethylphenyl) hydroxymethyl] (Compound 31) with an oxidizing agent, such as 3-chloro-peroxybenzoic acid, producing the N-oxide corresponding, for example, N- [4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine N-oxide (Compound 32). provides a detailed description of how this reaction is conducted The following examples illustrate general methods by which the compounds of the present invention were prepared.
EXAMPLE 1 Synthesis of N- (4-Methoxy in i I met I, -4-1bis (4-trif luoro methoxyf enyl) -hydroxymethylpiperidine (Compound 1)
To a stirred mixture of 1.1 grams (0.045 grams-atom) of magnesium versions in 30 ml of diethyl ether was added dropwise 15 ml of a solution of 11.0 grams (0.045 moles) of bromide 4- trifluoromethoxyphenyl in 30 ml of diethyl ether. Once the reaction was started, the remaining 15 ml of the bromide solution was added in portions over a period of 45 minutes. When the reaction decreased, a solution of 5.0 grams (0.018 moles) of ethyl N- (4-methoxyphenylmethyl) piperidin-4-ylcarboxylate in 10 ml of diethyl ether was added dropwise over a period of five minutes. After the end of the addition, the reaction mixture was heated to reflux, where it was stirred for about 30 minutes. The reaction mixture was then allowed to cool to room temperature, where it was stirred for about 18 hours. After this time, an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The mixture was then partitioned between water and diethyl ether. The diethyl ether layer was separated and washed first with a solution saturated with sodium chloride and then with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel, with 10% diethyl ether in hexane, 100% diethyl ether, and 10% methanol in diethyl ether as eluents. The fractions containing the product were combined and concentrated under reduced pressure, yielding 6.7 grams of N- (4-methoxyphenylmethyl) -4-] bis (4-trifluoromethoxyphenyl) -hydroxymethyl] piperidine, m.p. 86-69 ° C. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 2 Synthesis of Nr2- (4-Methoxyphenyl) -4-bis (4-trifluoromethoxyphenyl) -hydroxymethylpiperidine (Compound 2)
Step A Synthesis of ethyl N- [22- (4-methoxyphenyl) ethyl] piperidin-4-yl-carboxylate as an intermediate A stirred mixture of 5.0 grams (0.032 moles) of ethyl piperidin-4-ylcarboxylate, 5.4 grams ( 0.32 moles) of 1- (2-chloroethyl) -4-methoxybenzene and 4.4 grams (0.032 moles) of potassium carbonate in 50 ml of dry N, N-dimethylformamide was heated at 70 ° C for about 16 hours. After this time, the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether / hexane mixtures as eluents. The fractions containing the product were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N- [2- (4-methoxyphenyl) ethyl] -piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.
Step B: Synthesis of N- [2- (4-methoxyphenyl) ethyl] -4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine (Compound 2) This compound was prepared in a manner analogous to that of Example 1, with 1. 6 grams (0.005 moles) of ethyl N- [2- (4-methoxyphenyl) ethyl] -piperidin-4-ylcarboxylate, 2.4 grams (0.010 moles) of 4-trifluoromethoxyphenyl bromide, and 0.3 grams (0.01 1 gram-atom) ) of magnesium versions in approximately 35 ml of diethyl ether as reagents. This reaction differed from Example 1 in that once the Grignard reaction begins, ethyl N- [2- (4-methoxyphenyl) ethyl] piperidin-4-ylcarboxylate is added to the diethyl ether solution of 4-trifluoromethoxyphenyl bromide. The combination was then added dropwise to the reaction mixture, thus introducing the piperidin-4-ylcarboxylate into the reaction mixture as the Grignard reagent was formed. After the end of the addition, the reaction mixture was stirred at room temperature for about 18 hours. After this time, an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The reaction mixture was then extracted with methylene chloride. The combined extracts were washed with a dilute aqueous solution of hydrochloric acid and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with combinations of hexane / diethyl ether and ethyl acetate / methanol as eluents. A second column chromatography on silica gel, with diethyl ether as the eluent, was required to provide the pure product. The fractions containing the product were combined and concentrated under reduced pressure, yielding 0.3 grams of N- [2- (4-methoxyphenyl) ethyl] -4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] -piperidine. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 3 Alternative Synthesis of 4-rbis (4-trifluoromethoxyphenyl) -hydroxymethylpiperidine To Be Used as an Intermediary
Step A Synthesis of ethyl N- (trimethylsilyl) piperidin-4-ylcarboxylate as an intermediate Under a nitrogen atmosphere, a stirred solution of 100.0 grams (0.64 moles) of ethyl piperidin-4-ylcarboxylate and 94 ml (0.67 moles) of triethylamine in 1400 ml of diethyl ether was cooled to 15 ° C, and a solution of 86 ml (0.68 moles) of chlorotrimethylsilane in 100 ml of diethyl ether was added dropwise over a period of 30 minutes. After the completion of the addition, the thick reaction mixture was stirred vigorously for one hour, while heating to room temperature. The reaction mixture was then filtered, and the solid was collected and washed with diethyl ether. The combined wash and filtrate were concentrated under reduced pressure to a residual oil. The oil was distilled under reduced pressure, yielding 15.0 grams (79% yield) of ethyl N- (trimethylsilyl) piperidin-4-ylcarboxylate, p. and. 75 ° C / 0.1 mm Hg. The NMR spectrum was consistent with the proposed structure.
Step B: Synthesis of 4- [bis (trifluoromethoxyphenyl) hydroxymethyl-piperidine as an intermediate A stirred mixture of 5.0 grams (0.021 moles) of 4-trifluoromethoxyphenyl bromide, 13.8 grams (0.570 grams-atom) of magnesium versions, and an iodide crystal in 25 ml of anhydrous tetrahydrofuran was heated to 50-60 ° C. Once the Grignard reaction started, 500 ml of anhydrous tetrahydrofuran was added, and the temperature of the reaction mixture was adjusted to 45 ° C. To this was added a solution of 53.0 (0.230 moles) of ethyl N- (trimethylsilyl) piperidin-4-ylcarboxylate and 128.8 grams (0.534 moles) of 4-trifluoromethoxyphenyl bromide in 475 ml of anhydrous tetrahydrofuran at a rate to maintain The temperature of the reaction mixture at 45-55 ° C. After the end of the addition, the reaction mixture was heated to reflux for about two hours, after which the reaction mixture was poured into a stirred mixture of 550 ml of an aqueous solution saturated with ammonium chloride and 200 grams of ice. The mixture was then extracted with 650 ml of ethyl acetate. The organic layer was stirred with a 250 ml portion of an aqueous solution saturated with sodium bicarbonate, a 250 ml portion of an aqueous 10% sodium hydroxide solution, and with two 200 ml portions of a saturated aqueous solution. with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 10 grams of residual oil. The oil was titrated with 500 ml of petroleum ether, and 67.0 grams of 4- [bis (trifluoromethoxy-phenyl) hydroxymethyl] piperidine were collected by filtration. The filtrate was cooled, and 15.5 grams of 4- [bis (trifluoromethoxyphenyl) -hydroxymethyljpiperidine were collected by filtration. The total production was 82%. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 4 Synthesis of N-f4- (Methylcarbonylamino) phenylmethyl-4-fbis (4-trifluoromethoxyphenyl) hydroxymethylpiperidine (Compound 3)
Step A: Synthesis of N-phenylmethyl-4- [bis (4-trifluoromethoxy-phenyl) hydroxymethyl] piperidine The compound was prepared in a manner analogous to that of Step B of Example 2, with 6.0 grams (0.024 moles) of N-phenylmethylpiperidine. Ethyl 4-ethylcarboxylate, 1.8 grams (0.073 grams-atom) of magnesium versions, and 17.5 grams (0.73 moles) of 4-trifluoromethoxy-phenyl bromide in about 80 ml of tetrahydrofuran as reagents. The production of N-phenylmethyl-4- [bis (4-trifluoromethoxyphenyl) -hydroxymethyl] piperidine was 9.7 grams. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of N-Phenylmethyl-4- [bis (4-trifluoromethoxy-phenyl) hydroxymethyl] piperidine hydrochloride as an intermediate
A solution of 1.0 grams (0.002 moles) of N-phenylmethyl-4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine in 30 ml of diethyl ether was cooled to 0 ° C, and hydrogen chloride was bubbled thereinto. An oily solid precipitate formed. After the end of the precipitation, the reaction mixture took up to 25 ml of hexane and was stored in a refrigerator for about 18 hours. After this time, the supernatant liquid was decanted from the precipitate. The precipitate was then stirred with about 20 ml of diethyl ether, and the mixture was concentrated under reduced pressure to a residue. The solid residue was stirred with about 20 ml of hexane, which was then decanted from the solid. The solid was dried under reduced pressure, yielding 0.8 grams of N-phenylmethyl-4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine hydrochloride. The NMR spectrum was consistent with the proposed structure.
Step C: Synthesis of 4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine as an intermediate. Under a nitrogen atmosphere, 0.8 grams of 10% palladium on carbon (catalyst) was placed in a reaction vessel. To this was cautiously added 25 ml of nitrogen-purged methanol, a solution of 0.8 grams (0.001 mole) of N-phenylmethyl-4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] -piperidine hydrochloride in 10 ml of methanol, and then 0.9 grams (0.010 moles) of formate d ammonium. After the addition was complete, the reaction mixture was heated to reflux for about 45 minutes. The reaction mixture was then cooled to room temperature and diluted with 1: 1 methylene chloride / methanol. The mixture was filtered through a pad of diatomaceous earth / glass fiber, and the filtrate was concentrated at about 30 ° C under reduced pressure to a residue. The residue was taken up in about 70 ml of ice / water and made basic with a 5% aqueous sodium hydroxide solution. The mixture was extracted with methylene chloride, and the extract was washed with an aqueous solution saturated with sodium chloride. The organic layer was then dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was stirred with petroleum ether, and 0.5 grams of 4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine were collected by filtration. The NMR spectrum was consistent with the proposed structure.
Step D Synthesis of N- [4- (methylcarbonylamino) phenylmethyl-4- [bis (4-trif luoro methoxyfyl) h id roxy methy] piperidin (Compound 3) To a stirred solution of 0.4 gram (0.0008 mole) of 4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine in 10 ml of dimethyl sulfoxide was added to a mixture of 0.2 grams (0.0008 mole) of 4- (methylcarbonylamino) phenylmethyl chloride and 0.6 ml (0.003 mole) of N , N-diisopropylethylamine. After the end of the addition, the reaction mixture was stirred at room temperature for about 18 hours. After that time, the reaction mixture was partitioned between a saturated aqueous solution with sodium bicarbonate and ethyl acetate. The organic layer was separated and washed with an aqueous solution saturated with sodium chloride. The organic layer was then concentrated under reduced pressure to a residue, it was subjected to column chromatography on silica gel, with methylene chloride and mixtures of 10-50% acetone in methylene chloride as eluents. The fractions containing the product were combined and concentrated under reduced pressure, yielding approximately 0.3 grams of N- [4- (methylcarbonyl-amino) phenylmethyl] -4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 5 Synthesis of N- (4-Propoxyphenylmethyl) -4bis (4-trifluoromethylphenyl) hydroxymethylpiperidine (Compound 102)
Step A Synthesis of 4-propoxyphenylmethyl chloride as an intermediate A mixture of 53.8 grams (.33 moles) of 4-propoxybenzaldehyde, 200 ml of ethanol and 200 ml of tetrahydrofuran was stirred, and 3.3 grams (0.09 moles) of sodium borohydride were added. they were added in portions during a period of 30 minutes. The reaction caused the temperature of the reaction mixture to increase to about 45 ° C. After the end of the addition, the reaction mixture was stirred for one hour and then emptied into 500 ml of water containing 50 grams of ammonium chloride. The mixture was extracted with two 500 ml portions of diethyl ether, and the combined extracts were washed with a 500 ml portion of an aqueous solution saturated with sodium chloride: The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 53.6 grams of a white solid. The solid was dissolved in 75 ml of methylene chloride and 0.75 ml of pyridine was added. The solution was added dropwise to a cooled (10 ° C) stirred solution of 28 ml (0.38 mole) of thionyl chloride in 350 ml of methylene chloride. The complete addition required one hour, during which the time of the reaction mixture was maintained at 10 ° C. After the end of the addition, the reaction mixture was stirred for one hour and emptied into a solution of 350 ml of water containing 100 ml of an aqueous solution saturated with ammonium chloride. The organic layer was washed with two 250 ml portions of an aqueous solution saturated with sodium bicarbonate, and dried with magnesium chloride. The mixture was filtered and the filtrate was concentrated under reduced pressure, yielding 56.4 grams of the material. The material was distilled under reduced pressure, yielding 52.5 grams of 4-propoxyphenylmethyl chloride, e.g. 92 C / 0.3 mm Hg.
Step B Synthesis of ethyl N- (4-propoxyphenylmethyl) piperidi n-4-ylcarboxylate as an intermediate To a stirred solution of 47.5 grams (0.03 mole) of ethyl piperidin-4-ylcarboxylate in 70 ml (0.40 mole) of N , N-diisopropylethylamine was added dropwise to a solution of 52.5 grams (0.29 mole) of 4-propyxyphenylmethyl chloride in 50 ml of dimethyl sulfoxide. The reaction caused the temperature of the reaction mixture to increase to about 35 ° C. After the end of the addition, the reaction mixture was stirred for 30 minutes, heated to 40 ° C and then allowed to cool to room temperature. After this time, the reaction mixture was poured into 500 ml of 10% aqueous ammonium chloride. The mixture was extracted with three 250 ml portions of diethyl ether, and the combined extracts were washed with two 250 ml portions of an aqueous solution saturated with ammonium chloride, a 250 ml portion of water, and a 250 ml portion. of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 80.0 grams of ethyl N- (4-propoxyphenyl-methyl) piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of N- (4-propoxyphenylmethyl) -4- [bis (trifluoromethylphenyl) hydroxymethyl] piperidine (Compound 102) This compound was prepared in a manner analogous to that of
Step B of Example 2, with 1.5 grams (0.005 moles) of N- (4-propoxy-phenylmethyl) piperidin-4-ylcarboxylate-style, 3.4 grams (0.015 moles) of 4-trifluoromethylphenyl bromide, and 0.4 grams (0.015 grams-atom) of magnesium versions in 15 ml of tetrahydrofuran as reagents. The crude product was subjected to column chromatography on silica gel, with 1: 1 ethyl acetate: heptane as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 1.4 grams of N- (4-propoxyphenylmethyl) -4- [bis (trifluoromethylphenyl) hydroxymethyl] piperidine. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 6 (Illustrative) Synthesis of N-r4- (2-ethylbenzoxazol-5-yl) metill-4-rbis (4- trifl uo rometoxifen i I) h id roxi metí ll Piperidina
Step A Synthesis of ethyl 3-nitro-4-hydroxybenzoate as an intermediate To a stirred solution of 20.0 grams (0.12 mole) of ethyl 4-hydroxybenzoate in 200 ml of acetic acid was added a solution of 7.5 ml (excess) of 70% of nitric acid in 30 ml of acetic acid. After stirring the reaction mixture for about 1 hour, it gradually became orange and heated to about 40 ° C. The reaction mixture was stirred for an additional 18 hours and then was poured into 800 ml of ice-water. The mixture was stirred until the ice was melted and filtered to collect a solid, which was dissolved in ethyl acetate and dried over magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure, yielding 22.0 grams of ethyl 3-nitro-4-hydroxybenzoate, mp 70-71 ° C. The NMR spectrum was consistent with the proposed structure.
Step Synthesis of Ethyl (2-ethylbenzoxazol-5-yl) carboxylate as an intermediate A mixture of 10.4 grams (0.05 moles) of ethyl 3-nitro-4-hydroxybenzoate, 0.3 grams of platinum oxide (catalyst) in 200 ml of ethyl acetate was stirred in a Parr hydrogenator until the theoretical amount of hydrogen was collected. The mixture was filtered to remove the catalyst, and the filtrate was concentrated under reduced pressure, yielding 9.6 grams of ethyl 3-amino-4-hydroxybenzoate as a solid. The NMR spectrum was consistent with the proposed structure. This 3-amino derivative, 9.0 grams (0.05 moles), was dissolved in 500 ml of ethanol and 9.7 grams (0.06 moles) of triethyl ortho-propionate were added. The reaction mixture was refluxed for three hours, then cooled to room temperature and concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, with 1: 4 ethyl acetate: heptane as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 8.7 grams of ethyl (2-ethylbenzoxazol-5-yl) carboxylate, m.p. 35-37 ° C. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of (2-ethylbenzoxazol-5-yl) methanol as an intermediate A stirred solution of 8.0 grams (0.037) of ethyl (2-ethylbenzoxazol-5-yl) carboxylate in 100 ml of anhydrous tetrahydrofuran was cooled to 0 ° C, and 20 ml (0.02 moles) of a 1.0 molar solution of lithium aluminum hydride in tetrahydrofuran was added in portions from a syringe. After the end of the addition, the reaction mixture was stirred at 0 ° C for 15 minutes, then allowed to warm to room temperature, where it was stirred for about 18 hours. The reaction mixture was poured into a mixture of 250 ml of an aqueous solution saturated with ammonium chloride and ice. The mixture was then extracted with two 250 ml portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium chloride, dried with magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with ethyl acetate as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 4.1 grams of (2-ethylbenzoxazol-5-yl) methanol. The NMR spectrum was consistent with the proposed structure.
Step D Synthesis of ethyl N- (2-ethylbenzoxazol-5-ylmethyl) piperidin-4-ylcarboxylate as an intermediate To a stirred solution of 3.4 grams (0.019 mole) of (2-ethylbenzoxazol-5-yl) methanol in 25 ml of toluene was added 1.6 grams (0.006 moles) of phosphorous tribromide from a syringe. Immediately a precipitate formed, and additional toluene was added to the reaction mixture to aid the agitation. The reaction caused the temperature of the reaction mixture to increase to about 35 ° C. After the end of the addition, the reaction mixture was stirred for an additional 20 minutes. The reaction mixture was then concentrated under reduced pressure to a residual solid. The solid was dissolved in 30 ml of dimethyl sulfoxide and, with stirring, 3.7 grams (0.029 mole) of N, N-diisopropylethylamine and 3.1 grams (0.019 mole) of ethyl piperidin-4-ylcarboxylate were added simultaneously from syringes . The resulting reaction caused the temperature of the reaction mixture to increase to about 40 ° C. The reaction mixture was allowed to cool to room temperature, as it was stirred for about 18 hours. The reaction mixture was evacuated and extracted with ethyl acetate and then with diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium bicarbonate, and then with an aqueous solution saturated with sodium chloride. The organic layer was concentrated under reduced pressure to a residual oil, which was subjected to column chromatography on silica gel, with ethyl acetate as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 2.1 grains of ethyl N- (2-ethylbenzoxazol-5-ylmethyl) piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.
Step E Synthesis of N- [4- (2-ethylbenzoxazol-5-yl) methyl] -4- [bis (4-trifluoromethoxy-phenyl) -hydroxymethyl] pipe ridine This compound was prepared in a manner analogous to that described in Step B of Example 2, with 1.9 grams (0.006 moles) of ethyl N- (2-ethylbenzoxazol-5-ylmethyl) piperidin-4-ylcarboxylate, 3.6 grams (0.015 moles) of 4-trifluoromethoxyphenyl bromide, and 0.4 grams ( 0.015 grams-atom) of magnesium versions in 35 ml of tetrahydrofuran as reagents. The crude reaction product was subjected to column chromatography on silica gel, with methylene chloride and then ethyl acetate as eluents. The fractions containing the product were combined and concentrated under reduced pressure, yielding 2.1 grams of N- [4- (2-ethylbenzoxazol-5-yl) methyl] -4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 7 Synthesis of N-r4- (2-methyl-2H-tetrazol-5-yl) phenyl-methyl-4-bis (4-trifluoromethoxy-phenyl) -hydroxy-methyl-piperidine (Compound 9)
Step A Synthesis of 4- (2-methyl-2H-tetrazol-5-yl) benzaldehyde as an intermediate A stirred solution of 2.2 grams (0.009 mole) of bromide 4- (2-methyl-2H-tetrol-5-yl) ) phenyl in 70 ml of dry tetrahydrofuran, cooled to -70 ° C, and 7.4 ml (0.018 mole) of n-butyllithium (2.5 M in hexanes) were added dropwise from a syringe. The resulting reaction caused the temperature of the reaction to increase to about -50 ° C. The reaction mixture was cooled again to -70 ° C, and stirring was continued for about 30 minutes. After this time, 0.8 ml (0.10 mole) of N, N-dimethylformamide was added over a period of 90 seconds. The reaction mixture was then stirred for 30 minutes at the temperature of the ice-water bath, after which it was allowed to warm to room temperature. The reaction mixture was poured into 200 ml of an aqueous solution saturated with ammonium chloride. The mixture was stirred for about 90 minutes and then extracted with three 150 ml portions of ethyl acetate. The combined extracts were washed with a 400 ml portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to an oily oil, which was subjected to column chromatography on silica gel, with 3: 7 ethyl acetate: heptane as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 0.5 grams of 4- (2-methyl-2H-tetrazol-5-yl) benzaldehyde. The NMR spectrum was consistent with the proposed structure.
Step B: Synthesis 4- (2-methyl-2H-tetrazol-5-yl) phenylmethanol as an intermediate This compound was prepared in a manner analogous to that of Step A of Example 5, with 0.5 grams (0.003 moles) of 4- ( 2-methyl-2 H-tetrazol-5-yl) benzaldehyde and 0.1 gram (0.003 mole) of sodium borohydride in 17 ml of ethanol. The production of 4- (2-methyl-2H-tetrazol-5-yl) phenylmethanol was approximately 0.4 grams. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of 4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl bromide as an intermediate This compound was prepared in a manner analogous to that of Step D of Example 6, with 0.4 grams (0.002 mole) of 4- (2-methyl-2 H-tetrazol-5-yl) phenylmethanol and 0.07 ml (0.0007 mole) of phosphorus tribromide in 7 ml of tetrahydrofuran as the reactants. The production of 4- (2-methyl-2H-tetrazo-5-yl) phenylmethyl bromide was 0.7 grams, which was used in the next reaction without further characterization.
Step D: Synthesis of N- [4- (2-methyl-2H-tetrazol-5-yl) phenyl-methyl] -4- [bis (4-trifluoromethoxyphen-I) hydroxymethyl] piperidine (Compound 9) This compound was prepared in the manner analogous to that of Step D of Example 4, with 0.3 grams (0.001 moles) of 4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl bromide, 0.5 grams (0.001 moles) of 4- [ bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine (prepared as in Step C of Example 4), and 0.6 grams (or 0.004 moles) of N, N-diisopropylamine in about 5 ml of dimethyl sulfoxide as reagents. The crude reaction product was subjected to column chromatography on silica gel, with 3: 7 acetone methylene loride as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding approximately 0.2 grams of N- [4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethoxyphenyl) -hydroxymethyljpiperidine. . The NMR spectrum was consistent with the proposed structure.
EXAMPLE 8 Synthesis of N-f4- (4,5-dihydro-1-methyl-5-oxo-1 H-1, 2,4-triazole-4- D-phenylmethyl-4-bis (4-trifluoromethylphenyl) hydroxymethylpiperidine (Compound 12)
Step A Synthesis of 4,5-dihydro-1-methyl-5-oxo-4- (4-methyl-phenyl) -1 H-1, 2,4-triazole as an intermediate To a stirred solution of 3.5 grams (0.08 moles) of methylhydrazine in 50 ml of tetrahydrofuran, cooled to 0 ° C, 10.0 grams (0.08 moles) of 4-methylphenyl isocyanate were added dropwise. After the end of the addition, the reaction mixture was stirred at 0 ° C for 30 minutes, then allowed to warm to room temperature, where it was stirred for one hour. After this time, the reaction mixture was concentrated under reduced pressure to a residual solid. The solid was dissolved in 100 ml of dioxane and 1 1.1 grams (0.08 mole) of triethyl orthoformate and three drops of concentrated sulfuric acid were added. The reaction mixture was heated to reflux for about three hours, during which about 75 ml of an azeotrope of water-dioxane was collected by distillation, after which, the reaction mixture was stirred at room temperature for about 60 hours. The reaction mixture was then concentrated under reduced pressure to a residual solid. The solid was dissolved in about 150 ml of ethyl acetate, and washed with a 50 ml portion of an aqueous solution saturated with sodium bicarbonate and a 50 ml portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual solid, which was subjected to column chromatography on silica gel, with 3: 7 ethyl acetate: heptane as the eluent. The fractions containing the product were combined and concentrated under reduced pressure, yielding 5.6 grams of a non-cyclized intermediate of the intended product. This intermediate was then stirred with 10 ml of Eaton's Reagent (a 7.5% w / w solution of phosphorous pentoxide in methanesulfonic acid) for about 18 hours. The mixture was then poured into ice-water and the resulting precipitate was collected by filtration, yielding 3.3 grams of 4,5-dihydro-1-methyl-5-oxo-4- (4-methylphenyl) -1H-1, 2 , 4-triazole. The NMR spectrum was consistent with the proposed structure.
Step B: Synthesis of 4,5-dihydro-1-methyl-5-oxo-4- (4-bromo-methylphenyl) -1 H-1, 2,4-triazole as an intermediate To a stirred solution of 2.6 grams (0.013) moles) of 4,5-dihydro-1-methyl-5-oxo-4- (4-methylphenyl) -1H-1, 2,4-triazole in 150 ml of carbon tetrachloride was added 0.3 grams of benzoyl peroxide ( catalyst) and 2.5 grams (0.014 moles) of N-bromosuccinimide. The reaction mixture was heated to reflux for 3 hours, after which it was cooled and concentrated under reduced pressure, yielding 2.6 grams of 4,5-dihydro-5-oxo-4- (4-bromomeylphenyl) -1 H- 1, 2,4-triazole, which was used in the next reaction without further characterization.
Step C Synthesis of N- [4- (4,5-dihydro-1-methyl-5-oxo-1 H-1, 2,4-triazol-4-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl ) hydroxymethyl] piperidine (Compound 12) this compound was prepared in a manner analogous to that of Step D of Example 4, with 2.0 grams (0.007 moles) of 4,5-dihydro-1-methyl-5-oxo-4 - (4-bromomethylphenyl) -1H- 1, 2,4-triazole, 2.0 grams (0.005 mole) of 4- [bis (4-trifluoromethoxyphenyl) hydroxymethyl] piperidine (prepared as in Step C of Example 4), and 3.2 grams (0.025 moles) of N, N-diisopropylethylamine in about 15 ml of dimethyl sulfoxide as reagents. The crude reaction product was subjected to column chromatography on silica gel, with 2: heptane: ethyl acetate, and then pure ethyl acetate as eluents. The fractions containing the product were combined and concentrated under reduced pressure, yielding 1.6 grams of N- [4- (4,5-dihydro-1-methyl-5-oxo-1 H- 1,2,4-triazole- 4-yl) phenyl-methyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 9 Synthesis of N-r4- (2-methyl-2H-tetrazol-5-yl) phenylmetm-4-rbis (4-trifluoromethylphenhydroxymethylpiperidine (Compound 31)
This compound was prepared in the manner described in Step E of Example 6, with 2.4 grams (0.007 moles) of N- [4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl] piperidin-4-ylcarboxylate of ethyl, 2.8 ml (0.019 moles) of 4-trifluoromethylphenyl bromide and 0.4 grams (0.018 grams-atom) of magnesium versions in 50 ml of tetrahydrofuran. The production of N- [4- (2-methyl-2 H-tetrzol-5-yl) -phenyl-methyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine was 2.0 grams. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 10 Synthesis of N-r4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl-4-rbis (4-trifluoromethylphenyl) hydroxymethyl piperidine N-oxide (Compound 32)
A solution of 1.1 grams (0.002 moles) of N- [4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl-4- [bis (4-trifluoromethylphenyl) hydroxy methyl] piperidine (Compound 31 - prepared in Example 9) in 100 ml of methylene chloride was stirred, and 0.6 grams (excess) of 50-85% of 3-chloroperoxybenzoic acid was added thereto. After the end of the addition, the reaction mixture was stirred at room temperature for about one hour. After this time, the reaction mixture was washed with a 10% aqueous solution of sodium hydroxide. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 1.0 grams of N- [4- (2-methyl-2-H-tetrazol-5-yl) phen i-methyl] -4- [bis (4- trifluoromethylfen i I) hydroxy methyl] piperidine. The NMR spectrum was consistent with the proposed structure. The representative compounds prepared by the methods illustrated above are listed in Table 1. The characterization properties are given in Table 2.
Biological Data Candidate insecticides were incorporated to an artificial diet to evaluate the insecticidal activity against the tobacco budworm (Heliothis virescens [Fabricius]) in the following manner. Solutions for the supply of test chemicals in dimethyl sulfoxide, ranging from 50 micromolar to 0.005 micromolar. 100 microliters of each of the supply solutions was manually stirred in 50 ml of a molten artificial diet based on wheat germ (65-70 ° C). The 50 ml of the melted diet containing the test chemical was emptied uniformly into 20 cavities in the two outer rows on each side of a five-row, 25-well plastic tray. (Each cavity in the tray has a depth of approximately 1 cm, with an opening of 3 cm by 4 cm in the lip). The molten diet containing only the dimethyl sulfoxide at the levels used in the diet treated with the test chemical was emptied at the five cavities in the third (central) row of the tray. Each tray, therefore, contained a test chemical to an individual application regime, along with an untreated control. The application regimes, expressed as the negative log of the molar concentration, and the corresponding concentrations of the supply solution prepared for each regime are shown below:
Supply Solution Application Regime 50 micromolar 4 5 5 0.5 6 0.05 7 0.005 8
Worm larvae were placed from the individual second instar tobacco bud, selected in a growth stage to which they weighed uniformly around 5 mg each, in each cavity. After the end of the infestation, a transparent plastic sheet was heat sealed over the top of the tray through the use of a common household flat iron. The trays were kept at 25 ° C at a relative humidity of 60% for 5 days in a growth chamber. Lighting was set to 14 hours of light and 10 hours of darkness. After an exposure period of 5 days, mortality counts were taken, and the insects that survived were heavy. From the weights of the surviving insects that were fed in the treated diet compared with those insects that were fed with the untreated diet, the percentage of inhibition of growth caused by each test chemical was determined. From these data, the negative log of the concentration of the test chemical that provided 50% inhibition of growth (floor) was determined by linear regression, when possible, for each test chemical. Also, when possible, the negative log of the concentration of the test chemical that provided 50% mortality (pLCS0) was determined. Candidate insecticides with high pl50 values of the diet test for insecticidal activity were tested in foliar evaluations against the tobacco budworm, devastating beetworm (Spodoptera exigua [Hubner]), and caterpillar of the cabbage (Trichpl? Sia nor [Hubner [). In these tests against the tobacco budworm and the devastating worm of the beet, nine-day-old chickpea plants (Cicer arietinum) were sprayed with 1,406 kg / cm2 that ran on the upper and lower leaf surfaces with chemical test solutions to provide application regimes as high as 1000 ppm of the test chemical. The solvent used to prepare the solutions of the test chemical was 10% acetone or methanol (v / v) and 0.1% of the surfactant octylphenoxypolyethoxyethanol in distilled water.
Four replicas, each containing a chickpea plant, for each application regime of the test chemical, were sprayed, the treated plants were transferred to an awning, where they were kept until the spray dried. The four chickpea plants for each replica treated with the test chemical, as described above, were removed from their containers by cutting the rods just above the soil line. The leaves and cut stems of the four plants in each replica were placed in 226.8 gram paper cups, each containing a moistened filter paper. Five worms from the second instar (6 days old) tobacco bud or devastating beet worms (7-8 days old) were counted in each cup, being careful not to cause damage. An opaque plastic cap was placed on each cup, which was then held in a growth chamber for an exposure period of 96 hours at 25 ° C and 50% relative humidity. At the end of the 96-hour exposure period, the cups were opened, and the number of dead, dying and alive insects counted. Using insect counts, the efficacy of the test chemical was expressed as a percentage of control. The percentage of control was derived from the total number of dead insects (TD) plus the total number of dying insects (TM) as compared to the total number of insects (TI) in the test:% Control = TD + TM x 100 TI The condition of the test plants was also observed for phytotoxicity and for the reduction of feeding damage as compared to an untreated control. The leaf tests with caterpillar of the cabbage were conducted in the same way as described above, the difference being that plants of pinto bean (Phaseolus vulgaris) were used instead of chickpea plants. The compounds of the present invention were active in the diet test against the tobacco budworm. More than the 40 compounds listed in Table 1 exhibited pl50 values of 6.0 or greater. Compounds 9, 15, 31-34, 43, 53, 54, 72, 73, 95, 96, 98-101, 103 and 104 all exhibited pl50 values of 6.5 or greater. Table 3 gives the data of the insecticidal activity for the compounds tested in the diet test. The compounds of the present invention also showed insecticidal activity in the foliar test of good to excellent against the tobacco budworm, devastating worm of the beet and caterpillar of the cabbage. It can be seen in Table 4, that many compounds provided control of 80% or greater of one or more of the test insect species at a 100 ppm application rate in the foliar test. For insecticidal application, the active compounds are formulated to insecticidal compositions through the mixture, in an insecticidally effective amount, with auxiliaries and vehicle normally employed in the art to facilitate the dispersion of the active ingredients for the particular utility desired, recognizing the fact that the formulation and the mode of application of toxic can affect the activity of the material in a given application. Thus, for agricultural use, the insecticidal compounds of the present invention can be formulated as granules of a relatively large particle size, such as water-soluble or water-dispersible granules, as powders, as wettable powders, as emulsifiable concentrates, as solutions , or as any of the other known types, depending on the desired mode of application. These insecticidal compositions can be applied either as sprays diluted in water, or powders, or granules, to areas where insect control is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% as much as 95% or more by weight of the active ingredient. The powders are free-flowing mixtures of the active ingredients with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shells and cottonseed flours, and other organic and inorganic solids, which act as dispersants and vehicles for the toxic; these finely divided solids have an average particle size of less than about 50 microns. A typical powder formulation useful herein is one that contains 1.0 parts or less of the insecticidal compound and 99.0 parts of talc. The wettable powders are in the form of finely divided particles, which are easily dispersed in water or other dispersant. The wettable powder is finally applied to the site where insect control is desired, either as a dry powder or as an emulsion in water or other liquids. Typical vehicles for wettable powders include Fuller's earth, kaolin clays, silica, and other highly absorbent, easily wettable and inorganic diluents. Wettable powders are usually prepared to contain about 5-80% of the active ingredient, depending on the absorbency of the vehicle, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a wettable powder formulation contains 80.8 parts of the insecticidal compound, 17.9 parts of Palmetto clay, 1.0 parts of sodium lignosulfonate and 0.3 parts of sulfonated aliphatic polyester as wetting agents. Other useful formulations for insecticidal applications are emulsifiable concentrates (ECs), which are homogeneous liquid dispersible dispersions in water or other dispersant, and may consist entirely of the insecticidal compound and an liquid or solid emulsifying agent, or may also contain a liquid carrier , such as xylene, heavy aromatic naphthas, isophorone, or other volatile organic solvent. For insecticidal application, these concentrates are dispersed in water or another liquid vehicle, and normally applied as a spray to the area to be treated. The weight percentage of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general it comprises from 0.5 to 95% of the active ingredient by weight of the insecticidal composition. Fluid formulations with similar to ECs, except that the active ingredient is suspended in a liquid vehicle, usually water. Fluid formulations, such as ECs, may include a small amount of a surfactant, and contain an active ingredient in the range of 0.5 to 95%, often 10 to 50%, by weight of the composition. For the application, the flowable formulations can be diluted in water or another liquid vehicle, and are usually applied as a spray to the area to be treated. Moistening, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, alkyl and alkylsulphonates and sulfates and their sodium salts; polyaryl alkylaryl alcohols; sulfated higher alcohols; polyethylene oxides; sulphonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of the long chain mercaptans and ethylene oxide. Many other types of useful surfactants are commercially available. The surfactants, when used, typically comprise from 1 to 15% by weight of the composition. Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol or other suitable solvents. Still other useful formulations for insecticidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granulated formulations, in which the toxic is carried in relatively thick particles, are of particular utility for air distribution or for the penetration of cover awning for grains. Pressurized sprays, typically aerosols, wherein the active ingredient is dispersed in a finely divided form as a result of vaporization of a low boiling dispersant solvent vehicle, such as carbon dioxide, propane, or butane, may also be used. Water-soluble or water-dispersible granules are also useful formulations for insecticidal applications of the compounds herein. Said granulated formulations are free-flowing, non-dusting and easily soluble in water or miscible with water. The soluble or dispersible granulated formulations described in the patent of E.U.A. No. 3, 920,442 are useful herein with the insecticidal compounds herein. When used by the farmer in the field, granulated formulations, emulsifiable concentrates, flowable concentrates, solutions, etc. , can be diluted in water to give a concentration of the active ingredient in the range of 0.1% or 0.2% to 1.5% or 2%. The active insecticidal compounds of this invention can be formulated and / or applied with other insecticides, fungicides, nematicides, plant growth regulators, fertilizers, or other agricultural chemicals. By using an active compound of this invention, either formulated alone or with other agricultural chemicals, to control insects, an effective amount and concentration of the active compound is applied to the site where control is desired. The site can be, v. gr. , the same insects, the plants on which the insects feed, or the habitat of the insect. When the place is the earth, v. gr. , the land where the agricultural grains have been or will be planted, the composition of the active compound can be applied to and optionally incorporated into the soil. For most applications, the effective amount may be as low as, for example, about 10 to 500 g / ha, preferably about 100 to 250 g / ha. It is evident that various modifications can be made in the formulation and application of the compounds of this invention without departing from the inventive concepts herein, as defined in the inventive concepts defined herein, as defined in the appended claims.
TABLE 1
N- (alkyl substituted) -4-rdi (hydroxymethyl) substituted piperidines!
where V, W, Y, and 2 are hydrogen Comp. No. Comp. Do not.
5Hn TABLE 1 (Cont.)
Comp. No. Comp. Do not.
N-oxide
where U is - Res R1 v and R «2 • = • are (CH2) n-,
where V, W, Y, and 2 are hydrogen TABLE 1 (Cont.)
- NO-oxide
TABLE 1 (Cont.)
N-oxide
N-oxide
N-oxide OCH3 TABLE 1 (Cont.)
N-oxide
N-oxide
N-oxide TABLE 1 (Cont.)
N-oxide
TABLE 1 (Cont.)
N-oxide
N-oxide
N-oxide TABLE 1 (Cont.)
N-oxide N-oxide
N-oxide
TABLE 1 (Cont.)
N-oxide
N-oxide
102 -. 102 -OC3H7
where Q is -OH; U is- { CH2) n-.ßn where n is 1; and R is
where V, W, Y and 2 are hydrogen
TABLE 1 (Cont.)
where V, W.YyZ are hydrogen
Comp. No. Comp. Do not.
TABLE 2 Characterization Data
1 86-96 ßC 43 75-89
2 GEL 44 198-202 DEC
3 OIL 45 115-125 DEC.
4 OIL 46 171-191 DEC
FOAM 47 88-91 C
6 FOAM 48 214-215 DEC
7 240 DEC 49 80-85 C
8 FOAM 50 212-215 DEC
9 OIL 51 78-87
OIL 52 114-118 DEC
11 FOAM 53 71-77
12 FOAM 54 208-210
13 FOAM 55 104-120 DEC
14 SEMI-SOLID 56 166-186 DEC
165-170 C 57 78-82
18 90-95 58 209-213
19 91-94 59 105-110
125-128 60 77-83
21 226-228 61 208-212 DEC.
22 118-121 62 SOLID
23 200-202 63 SOLID
24 94-100 64 SOLID
SOLIDO BLANCO 65 105-113
26 110-120 66 SOLID
27 98-102 67 SOLID
28 203 DEC 68 72-77
29 OIL 69 153-159
188-190 70 69-77
31 57-62 71 215-220 DEC
32 > 200 72 82-85
33 60-65 73 216-220 DEC
34 > 210 74 179-182
SOLID WHITE 75 73-77
36 FOUNTAIN 76 144-145
37 77-80 77 170-174
38 70-74 78 61-68
39 142-148 79 199-204 DEC
40 65-67 80 214-217 DEC
41 OIL 81 54-68
42 210-211 82 210-215 DEC TABLE 2 (Cont.) Characterization Data
83 51-55 94 199-203
84 143-147 95 88-94
85 155-170 96 185-197 DEC
86 65-75 97 SOLID
87 SOLID 98 SOLID
88 188-194 99 SOLID
89 166-171 100 SOLID
90 80-88 101 SOLID
91 185-192 102 FOAM
92 203-206 103 FOAM GOMOSA SOLIDA 93 187-189 104 SOLIDA
CUADR O 3 Insecticide Activity When 1 Incorporates the Sprout Worm Diet d < a Tobacco Regime of% Inhibition% of 5 Comp. No. Application1 of Increase2-3 .504 Mortality p? C50? 1 4 100 * 6.1 * 100 * 4.6 * 2 4 98 5.6 25 < 4.0 3 4 95 4.7 0 ~ _
4 4 100 * 5.5 * 100 * 5.5 * 5 4 100 5.5 100 4.6
6 4 100 6.0 100 5.1 7 4 92 * 5.0 * 0 * - 8 4 79 * 4.5 * 0 * - 9 4 100 6.6 100 5.6
4 49 * 4.0 * 0 * -
11 3.5 2 - 0 _ 12 4 98 5.4 35 < 4.0
13 4 98 5.4 30 < 4.0
14 4 99 5.5 100 4.5
4 100 6.6 100 5.9
18 4 73 4.2 0 NM
19 4 98 4.5 90 4.4
4 93 5.3 10 < 3.5
21 4 95 5.0 10 < 3.5
22 4 99 5.5 35 3.9
23 4 100 5.5 65 4.2
24 4 86 4.5 0 < 3.5
4 33 3.8 0 NM
26 4 90 5.2 15 NM
27 4 100 6.2 100 5.5
28 4 100 5.6 100 5.1
29 4 98 5.2 60 4.2
4 98 5.1 40 < 4.0
31 4 100 6.5 100 5.6
32 4 100 6.5 100 5.6
33 4 99 6.6 100 6.1
34 4 100 6.5 100 5.9
4 100 6.4 100 5.5
36 4 100 6.1 100 5.4
37 4 100 5.5 100 5.4
38 4 100 6.2 100 5.6 TABLE 3 (Cont.)
% Inhibition% e ß BOX 3 (Cont.)% Inhibition% of 5 Comp. No. Application1 of Increment2'3 P < 504 Mortality pLC50e
78 4 100 6.0 100 4.5
79 4 100 6.0 100 4.5
80 4 96 5-2 15 NM
81 4 93 4.5 20 NM
82 4 93 4.7 25 < 4.0
83 4 100 6.0 100 4.5
84 4 100 6.0 100 4.6
85 4 88 5.2 0 NM
86 4 95 6.1 30 < 4.0
87 4 75 4.4 5 NM
88 4 74 4.6 10 NM
89 4 44 < 4.0 0 NM
90 4 38 < 4.0 10 NM
91 4 74 4.3 0 NM
92 4 43 < 4.0 20 NM
93 4 93 4.9 0 NM
94 4 88 4.7 0 NM
95 4 100 6.5 100 5.5
96 4 100 6.5 100 5.6
97 4 100 5.2 0 NM
98 4 100 6.6 100 6.5
99 4 100 6.5 100 6.4
100 4 100 6.5 100 6.4
101 4 100 6.5 100 5.4
102 4 100 > 6.0 100 5.5
103 4 100 6.5 100 4.9
104 4 100 6.8 100 6.4
The rate of application is expressed as the negative log of the molar concentration of the test compound in the diet. The percentage of inhibition of growth is derived from the total weight of the insects (IW) in each application regime in the test in relation to the total weight of the insects in an untreated control:
% Gr. Inh = ÍIW (control) - IW (control) l x 100 [IW (control)] A minimum growth inhibition% indicates that the insects weighed more at the end of the test than those in the untreated control. p o is the negative log of the concentration of the test chemical that provides 50% inhibition of growth in the test species. The percentage of mortality is derived from the number of dead insects (TD) in relation to the number of insects (TI) used in the test,
% Mortality = TD 100 TI
This is the negative log of the concentration of the test chemical that provides 50% mortality of the test insects. * Average of more than one test. NM is not measured.
TABLE 4 Insecticide Activity When Applied as Foliar Appearances
D t? Cng¡impiAc.i- uAc -_-. % of Control1 Comp. No. Application (ppm) TBW2 Cl3 BAW4
1 100 80 100 55 4 100 89 70 30 9 100 100 100 100 25 100 0 20 0 26 100 15 47 0 27 100 100 100 100 31 100 100 100 100 * 32 100 100 100 100 * 33 100 100 95 100 34 100 100 100 100 35 100 100 95 100 36 100 ** 97.5 ** 97.5 ** 100 **
43 100 100 95 100 44 100 100 100 100 49 100 100 100 100 50 100 100 100 100 53 100 100 ** 100 ** 94 ** 100 **
54 100 95 100 100 57 100 75 55 90 60 100 100 100 100 66 100 90 100 100 72 100 100 100 100 75 100 100 100 100 78 100 40 75 26 79 100 65 100 60 95 100 85 100 100 96 100 95 100 100 98 30 100 100 100 99 30 100 100 100 102 100 98 * 100 * 100 *
1 The control percentage is derived from the total number of dead insects (TD) plus the total number of moribund insects (MT) as compared to the total number of insects (TI) used in the test:% Control = TD + TM x 100 TI 2 TBW is the tobacco budworm (Heliothis veriscens)
[Fabricius]) 3 CL is the caterpillar of the cabbage (Trochoplusia ni [Hubner]) 4 BAW is the devastating worm of the beet (Spodoptera exigua [Hubner]) * Average of more than one test.
Claims (8)
- CLAIMS A compound of the formula: wherein: U is - (CH2) "; Q is hydroxy; R is wherein, V, W, Y, Z are each hydrogen; X is a 5-6 membered heterocycle; optionally substituted with halogen, alkyl, alkoxy, alkoxyalkyl, cyano, aminocarbonyl, haloalkyl, haloalkoxy, haloalkoxyalkyl; and the heterocycle is optionally connected to the phenyl ring through a ligation -O-, -S-, - (CH2) P, -C (O) -, or -O- (CR3R4) q; R1 and R2 are independently selected from phenyl or pyridyl substituted with haloalkyl or haloalkoxy; R3 and R4 are independently selected from hydrogen and methyl; n and p are independently 1, 2, or 3; and q is 1 or 2; with the proviso that at least one of R1 and R2 is substituted in the para position; no more than two of R3 and R4 are methyl; each aliphatic portion contains from 1 to 4 carbon atoms; halogen means bromide, chloride or fluoride; each heterocycle contains from 1 to 4 carbon atoms, or 1 or 2 oxygen or sulfur atoms, or 1 or 2 nitrogen atoms and an oxygen or sulfur atom; and the corresponding N-oxides the agriculturally acceptable salts.
- 2. A compound according to claim 1, wherein in X, the heterocycle is selected from 1,4-oxadiazol-5-yl, oxazolin-2-yl, pyrazol-3-yl, pyridin-2- ilo, pyrimidin-2-yl, pyrol-3-yl, 2H-tetrazol-5-yl, 1, 2, 3-thiadiazol-4-yl, and 1, 2,4-triazol-3-yl, optionally substituted with halogen, alkoxy alkyl, alkoxyalkyl, cyano, aminocarbonyl or haloalkyl and the optional linkage is selected from -O-, - (CH2) p-, -C (O) -, or -O- (CHR3) q .; R1 and R2 are independently selected from trifluoromethyl-phenyl, trifluoromethoxyphenyl, 5-trifluoromethylpyrid-2-yl, and 5-trifluoro-methoxypyrid-2-yl; n is 1 and p and q are independently selected from 1 and 2; whenever halogen means chlorine or fluorine.
- 3. A compound according to claim 2, wherein in optional X, the substituent is selected from alkyl, alkoxy, cyano, - (CH2) rF, wherein r is 1, 2 or 3, CHF2, CF3, and CH2OCH3; the optional ligature is selected from -O-, -O-CH2-, and -O-CH (CH3); and both R1 and R2 are substituted in the para position.
- 4. A compound according to claim 3, wherein R1 and R2 are independently selected from trifluoromethyl phenyl and trifluoromethoxyphenyl.
- 5. A compound according to claim 4, wherein in the heterocycle X is 2H-tetrazol-5-yl substituted in the 2-position.
- 6. A compound according to claim 5, which is N- [ 4- (2-methyl-2 H -tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hyd roxymethyl] pipe ridine.
- 7. A compound according to claim 5, which is N- [4- (2-methyl-2H-tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl N-oxide. ] piperidine.
- 8. A compound according to claim 5, which is N- [4- (2-ethyl-2H-tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine. 9 - A compound according to claim 5, which is N- [4- [2- (2-fluoroethyl) -2H-tetrazol-5-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxy metí I] pipe ridina. 10. A compound according to claim 4, wherein in the heterocycle, X is pyridin-2-yl, optionally substituted in the 6-position. 1-A compound according to claim 10, which is N- [4- (pyridin-2-yl) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine. 12. A compound according to claim 10, which is N- [4- (pyridin-2-yloxy) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine. 13. A compound according to claim 4, wherein in the heterocycle, X is pyrimidin-2-yl, optionally substituted in the 4-position. 14. A compound according to claim 13, which is N- [4- (pyrimidin-2-yloxy) phenylmethyl] -4- [bis (4-trifluoromethylphenyl) hydroxymethyl] piperidine. 15. A compound according to claim 12, which is N- [4- (pi rim id i n-2-yl) f-enyl methyl] -4- [bis (4-trifluoro methylphenyl) hydroxy- methyl] piperidine. 16. A compound according to claim 3, wherein R1 and R2 are independently selected from 5-trifluoromethylpyrid-2-yl and 5-trifluoromethoxy-pyrid-2-yl. 17. A compound according to claim 16, which is N- [4- (2-ethyl-2H-tetrazol-5-yl) phenylmethyl] -4- [bis (5-trifluoromethylpyrid-2-yl) hydroxymethyl. ] piperidine. 18. A composition containing an insecticidally effective amount of a compound according to claim 1 in admixture with at least one extensor or agriculturally acceptable auxiliary. 19. A method for controlling insects comprising applying to the site where control is desired, an insecticidally effective amount of a composition according to claim 18.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US44469895A | 1995-05-19 | 1995-05-19 | |
PCT/US1996/007206 WO1996036228A1 (en) | 1995-05-19 | 1996-05-17 | Insecticidal n-(substituted arylmethyl)-4-[bis(substituted phenyl or pyridyl)methyl]piperidines |
US444698 | 2006-06-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
MX9708891A MX9708891A (en) | 1998-03-31 |
MXPA97008891A true MXPA97008891A (en) | 1998-10-15 |
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