AP65A - Pestcidal compounds. - Google Patents
Pestcidal compounds. Download PDFInfo
- Publication number
- AP65A AP65A APAP/P/1986/000045A AP8600045A AP65A AP 65 A AP65 A AP 65A AP 8600045 A AP8600045 A AP 8600045A AP 65 A AP65 A AP 65A
- Authority
- AP
- ARIPO
- Prior art keywords
- phenyl
- octane
- group
- alkyl
- trioxabicyclo
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 153
- -1 4-dibromomethylphenyl Chemical group 0.000 claims abstract description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 135
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 125
- 239000000203 mixture Substances 0.000 claims description 111
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 239000001257 hydrogen Substances 0.000 claims description 65
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 37
- 125000000304 alkynyl group Chemical group 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 238000009472 formulation Methods 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 241000607479 Yersinia pestis Species 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000001246 bromo group Chemical group Br* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 239000005864 Sulphur Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- 230000000361 pesticidal effect Effects 0.000 claims description 8
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 239000011630 iodine Chemical group 0.000 claims description 6
- 229910052740 iodine Chemical group 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 206010061217 Infestation Diseases 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- WZWNCSJQQMWTMS-UHFFFAOYSA-N 1-ethyl-4-(4-ethynylphenyl)-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(CC)(CO2)COC12C1=CC=C(C#C)C=C1 WZWNCSJQQMWTMS-UHFFFAOYSA-N 0.000 claims description 3
- 230000000895 acaricidal effect Effects 0.000 claims description 3
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 238000007269 dehydrobromination reaction Methods 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 230000000749 insecticidal effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- RIZZXCJMFIGMON-UHFFFAOYSA-N prop-2-ynyl acetate Chemical compound CC(=O)OCC#C RIZZXCJMFIGMON-UHFFFAOYSA-N 0.000 claims description 3
- QVCOXWYMPCBIMH-UHFFFAOYSA-N prop-2-ynyl carbamate Chemical compound NC(=O)OCC#C QVCOXWYMPCBIMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- VXQAPGCBJDOBGN-UHFFFAOYSA-N 1-(2,2-dimethylpropyl)-4-(4-ethynylphenyl)-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(CC(C)(C)C)(CO2)COC12C1=CC=C(C#C)C=C1 VXQAPGCBJDOBGN-UHFFFAOYSA-N 0.000 claims description 2
- PEMCJTGVXDHHGC-UHFFFAOYSA-N 1-propyl-4-(4-prop-1-ynylphenyl)-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CC)C=C1 PEMCJTGVXDHHGC-UHFFFAOYSA-N 0.000 claims description 2
- VTUKKVHSZDBIPA-UHFFFAOYSA-N 3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC2COC1OC2 VTUKKVHSZDBIPA-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- FMLJQWIMQVSUMF-UHFFFAOYSA-N trimethyl-[2-[4-(1-propyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]ethynyl]silane Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#C[Si](C)(C)C)C=C1 FMLJQWIMQVSUMF-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 19
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- WUJXRLUSCOFFIK-UHFFFAOYSA-N 1-tert-butyl-4-[4-(3-methoxyprop-1-ynyl)phenyl]-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound C1=CC(C#CCOC)=CC=C1C1(OC2)OCC2(C(C)(C)C)CO1 WUJXRLUSCOFFIK-UHFFFAOYSA-N 0.000 claims 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims 1
- YJVVJOQVKMBUMF-UHFFFAOYSA-N 2-[4-(1-cyclohexyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]ethynyl-trimethylsilane Chemical compound C1=CC(C#C[Si](C)(C)C)=CC=C1C1(OC2)OCC2(C2CCCCC2)CO1 YJVVJOQVKMBUMF-UHFFFAOYSA-N 0.000 claims 1
- MDAICTYEICDMCR-UHFFFAOYSA-N 4-[4-(3-ethoxyprop-1-ynyl)phenyl]-1-propyl-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CCOCC)C=C1 MDAICTYEICDMCR-UHFFFAOYSA-N 0.000 claims 1
- OPVIBLCKPJHWAK-UHFFFAOYSA-N 4-[4-(4-methoxybut-1-ynyl)phenyl]-1-propyl-3,5,8-trioxabicyclo[2.2.2]octane Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CCCOC)C=C1 OPVIBLCKPJHWAK-UHFFFAOYSA-N 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- PTMCQFYJMIDACW-UHFFFAOYSA-N methyl 3-[4-(1-propyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]prop-2-ynoate Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CC(=O)OC)C=C1 PTMCQFYJMIDACW-UHFFFAOYSA-N 0.000 claims 1
- WUVLAIKRGCITRH-UHFFFAOYSA-N n-[3-[4-(1-propyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]prop-2-ynyl]acetamide Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CCNC(C)=O)C=C1 WUVLAIKRGCITRH-UHFFFAOYSA-N 0.000 claims 1
- HCJTYESURSHXNB-UHFFFAOYSA-N propynamide Chemical compound NC(=O)C#C HCJTYESURSHXNB-UHFFFAOYSA-N 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 abstract description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 abstract 1
- 150000001345 alkine derivatives Chemical class 0.000 abstract 1
- 238000007256 debromination reaction Methods 0.000 abstract 1
- 239000002917 insecticide Substances 0.000 abstract 1
- 239000000575 pesticide Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 44
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
- 229960004132 diethyl ether Drugs 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000007787 solid Substances 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 25
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 229910021529 ammonia Inorganic materials 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 238000001030 gas--liquid chromatography Methods 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000012442 inert solvent Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- YACFFSVYSPMSGS-UHFFFAOYSA-N 3-methoxyprop-1-yne Chemical compound COCC#C YACFFSVYSPMSGS-UHFFFAOYSA-N 0.000 description 10
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 10
- 241000238631 Hexapoda Species 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000007921 spray Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000451 chemical ionisation Methods 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 239000004495 emulsifiable concentrate Substances 0.000 description 7
- 229960005235 piperonyl butoxide Drugs 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 241000238421 Arthropoda Species 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000003350 kerosene Substances 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 4
- 239000004540 pour-on Substances 0.000 description 4
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- 241000254179 Sitophilus granarius Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241001492664 Solenopsis <angiosperm> Species 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- 238000000944 Soxhlet extraction Methods 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241001494139 Stomoxys Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000255626 Tabanus <genus> Species 0.000 description 1
- 241001454293 Tetranychus urticae Species 0.000 description 1
- 241000333689 Tineola Species 0.000 description 1
- 241000254086 Tribolium <beetle> Species 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 241001414985 Zygentoma Species 0.000 description 1
- GLYOPNLBKCBTMI-UHFFFAOYSA-N [2-chloro-2-(1-chloro-2-phenylethoxy)ethyl]benzene Chemical compound C=1C=CC=CC=1CC(Cl)OC(Cl)CC1=CC=CC=C1 GLYOPNLBKCBTMI-UHFFFAOYSA-N 0.000 description 1
- AOIYANWKFZQWRQ-UHFFFAOYSA-N [Na].[Na].CC(C)OS(=O)(=O)C1=CC=CC=C1 Chemical compound [Na].[Na].CC(C)OS(=O)(=O)C1=CC=CC=C1 AOIYANWKFZQWRQ-UHFFFAOYSA-N 0.000 description 1
- YSVDXOJUVQMPCX-UHFFFAOYSA-N [propoxy(prop-2-ynoxy)phosphoryl]benzene Chemical compound CCCOP(=O)(OCC#C)C1=CC=CC=C1 YSVDXOJUVQMPCX-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000005257 alkyl acyl group Chemical group 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 229960000892 attapulgite Drugs 0.000 description 1
- 239000005667 attractant Substances 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- VEMKTZHHVJILDY-UXHICEINSA-N bioresmethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UXHICEINSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 235000013339 cereals Nutrition 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
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
- 238000005828 desilylation reaction Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- FXORZKOZOQWVMQ-UHFFFAOYSA-L dichloropalladium;triphenylphosphane Chemical compound Cl[Pd]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FXORZKOZOQWVMQ-UHFFFAOYSA-L 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- LPTRPYKRNYNINY-UHFFFAOYSA-N diethyl 2-(2,2-dimethylpropyl)propanedioate Chemical compound CCOC(=O)C(CC(C)(C)C)C(=O)OCC LPTRPYKRNYNINY-UHFFFAOYSA-N 0.000 description 1
- RPNFNBGRHCUORR-UHFFFAOYSA-N diethyl 2-butylpropanedioate Chemical compound CCCCC(C(=O)OCC)C(=O)OCC RPNFNBGRHCUORR-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 244000078703 ectoparasite Species 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- NSNYHHADKMKJJE-UHFFFAOYSA-N ethyl 3-[4-(1-ethyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]prop-2-ynoate Chemical compound C1=CC(C#CC(=O)OCC)=CC=C1C1(OC2)OCC2(CC)CO1 NSNYHHADKMKJJE-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 231100001225 mammalian toxicity Toxicity 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 201000002266 mite infestation Diseases 0.000 description 1
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
- KKQCXOPSDOZLQK-UHFFFAOYSA-N n-methyl-3-[4-(1-propyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]prop-2-ynamide Chemical compound O1CC(CCC)(CO2)COC12C1=CC=C(C#CC(=O)NC)C=C1 KKQCXOPSDOZLQK-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052625 palygorskite Inorganic materials 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- GQOYBAHZFVZDEM-UHFFFAOYSA-N trimethyl-[2-[4-(1-pentyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)phenyl]ethynyl]silane Chemical compound O1CC(CCCCC)(CO2)COC12C1=CC=C(C#C[Si](C)(C)C)C=C1 GQOYBAHZFVZDEM-UHFFFAOYSA-N 0.000 description 1
- 150000004072 triols Chemical class 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- 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
- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K19/00—Liquid crystal materials
- C09K19/04—Liquid crystal materials characterised by the chemical structure of the liquid crystal components, e.g. by a specific unit
- C09K19/06—Non-steroidal liquid crystal compounds
- C09K19/34—Non-steroidal liquid crystal compounds containing at least one heterocyclic ring
- C09K19/3402—Non-steroidal liquid crystal compounds containing at least one heterocyclic ring having oxygen as hetero atom
- C09K2019/3422—Non-steroidal liquid crystal compounds containing at least one heterocyclic ring having oxygen as hetero atom the heterocyclic ring being a six-membered ring
- C09K2019/3425—Six-membered ring with oxygen(s) in fused, bridged or spiro ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Bicyclo-[2,2,1]-heptanes, bicyclo-[2,2,2]-octanes and bicyclo-[2,2,3]-nonanes having 2 or 3 ring hetero atoms selected from o, s and n, substituted at the 1-position by a 4-alkynylphenyl group and at the 4-position and optionally at the 3 and/or 5-position are valuable pesticides, particularly insecticides and acaracides. The compounds may be prepared by reacting an alkyne with the corresponding 4-iodophenyl substituted compound or by debromination of the corresponding 4-dibromomethylphenyl substituted compound.
Description
PESTICIDAL COMPOUNDS
The present invention relates to novel chemical compounds having pesticidal activity, to methods for their preparation, to compositions containing them and to their use in the control of pests. More particularly the invention relates to a class of heterobicycloalkanes.
The use of certain 2,6,7-trioxabicyclo[2,2,2]octanes is disclosed in European Patent Application No. 152229. It has now been discovered that derivatives of these compounds have interesting pesticidal activity.
Accordingly the present invention provides a compound of the formula (I)
wherein R is C2 jg alkyl, alkenyl or alkynyl, each optionally substituted by, or methyl substituted by, cyano, halo, Cj cycloalkyl alkoxy,or a group
4
S(O)mR where R is alkyl and m is 0, 1 or 2, or R is cycloalkyl, ^4-10 or Phenyl, each optionally substituted by alkoxy, j alkyl, C2.i1 al|<ynyb halo, cyano or a group SiO^R^ as defined hereinbefore;
r! and R^ may be the same or different, and is hydrogen, halo, j alkyl, C
2-3 alkenyl or alkynyl, the alkyl, alkenyl or alkynyl each being optionally substituted by halo, cyano,or alkoxy; alkyl carbalkoxy containing up to 6 carbon atoms, a group S(O) R^ as defined hereinbefore or alkynyl substituted by 1m tri-C^ alkylsilyl, or R is COO-C^-alkyl, cyano, gem dimethyl, gem dicyano, gem-dihalo, gem di-ethynyl, spiro-cyclopropyl, spiro-oxirane or spirooxetane, substituted spiro oxirane or spiro-oxetane, oxo or methylene optionally substituted by cyano , halo or trifluoromethyl or R and R and the carbon atoms to which they/.are-attachedUorm a carbocyclic ring optionally
AJR/EB$.9.86
-· t' ‘^D ORIGIN .0.
-, 2 P16 substituted by C^_3 alkyl or alkoxy or C2-3 adenyl;
5
F\ is a phenyl group substituted at the 4-position by a group -(C=C)nFv and optionally substituted at other positions of the phenyl ring, wherein n is 1 or 2, is hydrogen, bromine, chlorine, iodine, a group S(O) R^x wherein R^x is
Λ trifluoromethyl or a group R and m and R are as hereinbefore defined, an optionally substituted aliphatic or cycloaliphatic group containing up to 9 carbon atoms, a group -CX.R^ where X is oxygen or sulphur and R^ is a hydrocarbyl or hydrocarbyloxy group optionally substituted by fluoro or an amino group optionally substituted by one or two alkyl groups or R3 is cyano, or a silyi group substituted by three alkyl groups or two Cj_4 alkyl groups and a phenyl group;
Y and Y^ are the same or different and are each selected from oxygen and S(0) where m is 0, 1 or 2; Z is CR^CR^, CR^CR^O, sulphur, CR^O, CR^S, CHR^XNR^ 15 wherein Rlx is hydrogen, cyano, halo, a group CC^R^ or alkyl, C2 3 alkenyl or alkynyl each optionally substituted by halo, cyano, Δ alkoxy, alkyl carbalkoxy containing up to 6 carbon atoms or a group S(O) R4 wherein m and
7 m 8
R are as hereinbefore defined and R is hydrogen, benzyl, C-, Δ alkyl, C(O) R
9 9 14 wherein R is alkyl, alkoxy or a group NHR wherein R is alkyl, C? θ aralkyl or phenyl optionally substituted by halo or Z is -CO.CH,- or 20 in in lCH(OR )CH2-wherein R is hydrogen, alkyl, acyl or 3 carbamoyl, except that when R^ is hydrogen or a silyi group substituted by three alkyl groups and Y and Y are oxygen and Z is CR^O, then and R^ must be hydrogen.
In the definition of Z, the first mentioned atom is adjacent to the 4-position of the bicyclic ring system.
Suitably R is propyl, butyl, pentyl, alkenyl or alkynyl, y cycloalkyl or
3Q phenyl each optionally substituted by fluoro, chloro or bromo. Most suitably R is n-propyl,n-butyi, i-butyl, sec-butyl, t-butyl, cyclopentyl or cyclohexyl and preferably R is n-propyl, n-butyl, i-butyl, t-butyl or cyclohexyl.
Suitably R^ is hydrogen, cyano, methyl or ethyl each optionally substituted by cyano, methoxy, methylthio, chloro, bromo or fluoro. Most suitably R^ is 35 * 1 hydrogen, methyl, cyano, trifluoromethyl or ethyl. Preferably R is hydrogen, methyl, cyano or trifluoromethyl.
AP 0 0 0 0 6 5
BAD ORIGINAL $
AJR/EB/2.9.86
- 3 Ρ16 ? Μ Ο ο ο C)a
Suitable substituents on the phenyl group in R include halo, cyano, azido, nitro, j alkyl or alkoxy each optionally substituted by halo, or C2-3 elkenyl or alkynyl each optionally substituted by halo. Preferably the halo substituent will be fluoro, chloro or bromo. Suitably there are up to two substituents which are preferably at the 3- and/or 5-positions, but fluoro may also be at the 2-and/or 6positions.
Suitably is hydrogen, methyl or trifluoromethyl. Most suitably R^ is hydrogen.
Preferably n is 1.
Suitably R^ is hydrogen, optionally substituted methyl or ethyl, cyano, tri C, . 6 6 alkyl silyl or a group COR wherein R is alkyl or alkoxy or amino optionally substituted by one or two C^ alkyl groups. Suitable substituents when R^ is methyl or ethyl include hydroxy, a group OSO£R^^wherein R^^is
C} alkyl, phenyl or tolyl, alkoxy, Cj_^ acyloxy optionally substituted by an amino group mono or di substituted by Cj_^ alkyl groups or mono-substituted by phenyl optionally substituted by one to three halogen atoms, a group SCOR^ or S(O) R^ wherein m and R^ are as hereinbefore defined or a group NR^R^ m 11 12 wherein R is hydrogen or alkyl, R is hydrogen, C. alkyl or a group
C0r13 wherein R^ is alkyl or alkoxy or NR^R^ is a five or six membered heterocyclic ring. Most suitably is hydrogen, trimethylsilyl or substituted methyl or substituted ethyl, the substituents being hydroxy or methoxy.
Suitably Z is -CP^S-, -CP^O- or Preferably Z is -CP^S- or -CP^O-.
Suitably Y and Y^ are both oxygen.
One group of compounds of the formula is that of the formula (IA);
AJR/EB/9.9.86
- 4 P16 θ
wherein R is η alkyl, alkenyl or alkynyl, each optionally substituted by cyano, halogen or alkoxy, or R is cycloalkyl, cycloalkenyl or phenyl, each optionally substituted by alkoxy, alkyl, C2_^ alkynyl, halogen or cyano; R is hydrogen, alkyl, C2_^ alkenyl or alkynyl each optionally substituted by cyano, alkoxy, aikylthio, alkyl carbalkoxy ο 1 o containing up to 6 carbon atoms or halo, or R is cyano, gem dimethyl or R and R and the carbon atoms to which they are attached form a ? carbocyclic ring optionally substituted by alkyl, or C2_-j alkoxy or alkenyl;
R^a is a phenyl group substituted at the 4-position by a group -C=C-R^a and
1Q optionally substituted at other positions of the phenyl ring, wherein R^a is an optionally substituted aliphatic group, a group -C0.R^a where R^a is a hydrocarbyl or hydrocarbyioxy group or an amino group optionally substituted by one or two C, . alkyl groups or R is cyano, or a silyl group substituted by 3a three alkyl groups or two alkyl groups and a phenyl group; and R is hydrogen, Cj alkyl, C2 alkenyl or alkynyl each optionally substituted by cyano, aikylthio, alkoxy or halo; Ya and Y^a are the same or different and are each selected from oxygen or S(0)m where m is 0, 1 or 2; Za is CH2CH2, CH2CH20, sulphur, CH2O, CH2S or CR^NR?2 3 wherein R?a is hydrogen, benzyl, Cy alkyl, C(0) R^a wherein R^a is alkyl or alkoxy, or Z is -CO.CH2~ or 20 CH(OR^^a)CH2- wherein R^a is hydrogen, alkyl acyl or C·^ -j carbamoyl.
Suitably Ra is propyl, butyl, pentyl, C25 alkenyl or alkynyl, C^_7 cycioalkyl or phenyl each optionally substituted by fluoro, chloro or bromo. Most suitably Ra is n-propyl, i-butyl, sec-butyl, t-butyl, cyclopentyl or cyclohexyi and preferably
R is n-propyl, i-butyl, t-butyl or cyclohexyl.
Suitably R is hydrogen, cyano, methyl or ethyl each optionally substituted by cyano, methoxy, methylthio, chloro, bromo or fluoro. Most suitably R^a is g
3q hydrogen, methyl, trifluoromethyl or ethyl. Preferably R is hydrogen, methyl or trifluoromethyi
3
Suitable substituents on the phenyl group in R include halo, cyano, azido, nitro, *
alkyl or alkoxy each optionally substituted by halo, or C2 alkenyl or alkynyl each optionally substituted by halo. Preferably the halo substituent will be fluoro, chloro or bromo. Suitably there are up to two substituents which are preferably at the 3- and/or 5-positions.
AP ft ft ft 0 * 5
ba^oSginal
AJR/EB/2.9.86
- 5 Ρ16
3 s
Suitably R?a is hydrogen, methyl or trifluoromethyl. Most suitably R is hydrogen.
Suitably R^a is an optionally substituted methyl or ethyl group or a cyano or tri C1 4 9rouP or a 9rouP COR6a wherein R°a is alkyl or alkoxy or amino optionally substituted by one or two C, . alkyl groups. Suitable 5a substituents when R is methyl or ethyl include hydroxy, C, Δ alkoxy, C, .
11a 12a 11a 1-4 1-4 acyloxy, C. alkylthio or a group NR R wherein R is hydrogen or alkyl, R123 js hydrogen, C, , alkyl or a group CORlla wherein Rila is as lla 12a hereinbefore defined or NR R is a five or six membered heterocyclic ring.
*11 Most suitably R^a is methyl or ethyl substituted by hydroxy or methoxy or
V trimethylsilyl.
Suitably Za is -CH^S-, -CP^O- or -CP^CP^-. Preferably Z is -CP^S- or -CP^O-, the heteroatom being adjacent to the carbon atom substituted by R^a.
Suitably Ya and Y^3 are both oxygen.
Preferred compounds of the present invention include l-[3-nitro-4-(2-trimethylsilylethynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane l-(4-ethynylphenyI)-4-n-propyI-2,6,7-trioxabicyclo[2,2,2]octane
4-n-butyI-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane
4-i_-butyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane l-(4-ethynylphenyl)-4-n-pentyl-2,6,7-trioxabicyclo[2,2,2]octane
4-n-pentyI-l-[4-(2-trimethylsilylethynyl)phenyi]-2,6,7-trioxabicyclo[2,2,2]octane l-[3-chloro-4-(2-trimethylsiIylethynyl)phenyI]-4-n-propyl-2,6,7’trioxabicyclo[2,2,2joctane
4-propyl-l-[4-(2-trimethylsiiylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane l-[4-(3-methoxyprop-l-ynyl)phenyl]-4-propyI-2,6,7-trioxabicyclo[2,2,2]octane
4-n-butyl-l-[4-(2-trimethylsilylethynyI)phenyl]-2,6,7-trioxabicyclo(2,2,2]octane
4-Pbutyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo(2,2,2]octane l-[4-(3-ethoxyprop-l-ynyl)phenyl]-4-n-propyI-2,6,7-trioxabicyclo[2,2,2]octane
4-methoxy-l-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyI]but-l-yne
4-j-butyl-l-[4-(3-methoxyprop-l-ynyl-phenyl]-2,6,7-trioxabicyclo[2,2,2]octane
N-[3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyi}prop-2-ynyl acetamide
4-(2,2-di-methylpropyl)-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane methyl 3-[4-(4-n-propyi-2,6,7-trioxabicyclo[2,2,2)oct-l-yl)phenyl]prop-2-ynoate l-(3-chloro-4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane l-(4-ethynyl-3-nitrophenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
BAD ORIGINAL ¢5
AJR/EB/2.9.86
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Zi-^-butyl-l-^-ethynylphenyD^.S^-trioxabicycloR^Zloctane
4-cyciohexyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane
4-t-butyl-l-[4-(3-methoxyprop-l-ynyl)phenyI]-2,6,7-trioxabicyclo[2,2,2)octane
4-cyclohexyI-l-[4-(2-trimethylsiIylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2Joctane
4-ethyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo(2,2,2]octane
4-t-butyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane l-[3-chloro-4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
4-cyclohexyl-l-[4-(3-methoxyprop-l-ynyl)phenyl]2,6,7-trioxabicyclo[2,2,2]octane 4-n-butyl-l-(4-(3-metboxyprop-l-ynyJ)phenyl)2,6,7-trioxabjcyclof2,2,2]octane l-(4-(3-methoxyprop-l-ynyl)phenyl]-4-n-pentyl-2,6,7-trioxabicyclo(2,2,2]octane l-[4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propyl-3-tri fluoromethyl-2,6,7-trioxabicyclo[2,2,2]octane
3- cyano-l-(4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
4- (2,2-dime thy Ipropy 1)-1-[4-(3-methox yprop-l-yl)-phenyl)-2,6,7-trioxabicyclo[2.2.2] octane
4-(2,2-dimethylpropyl)-l-l4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2.2.2] octane
N-melhyl-3-[4-n-(4-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl)prop-2-ynyl carbamate
3-[4-(4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octyl)phenyl]prop-2-yn-l-ol
3- [4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l'yl)phenyI]prop-2-ynyl acetate
4- n-propyl-l-[4-(prop-l-ynyl)-phenyI]-2,6,7-trioxabicyclo[2,2,2]octane l-(4-(3-methoxyprop-l-ynyl)-phenyl]-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2) octane l-[4-(2-t^-butyldimethylsilylethynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2.2.2] octane
3.[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynylmethanesulphonate
N-methyl-3-(4-(4-n-propyl-2,6,7-trioxabicyclo(2,2,2]oct-2-yl)phenyl]-prop-2ynamide
N-methyl-3-(4-(4-n-propyl-2,6,7-trioxabicyclo(2,2,2]oct-l-yl)phenyl]-prop-2ynthioamide
4-n-butyl-l-[4-(3-methoxyprop-l-yny l)phenyl]-3-tri fluoromethy 1-2,6,7-trioxabicyclo[2,2,2]octane l-[4-(pent-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2)octane l-(4-ethynylphenyl)-4-phenyl-2,6,7-trioxabicyclo£2,2,2}octane
4-Pheny1-1-(/1-(2-trimethylsilylethynylphenyl )J-2,6,7-trioxabicyclo[2,2,2]octane
4-n-propyl-l-[4-(2-trimethylsilylethynylphenyl)3-2,6-dioxa-7-thiabicyclo[2,2,2joctane l-(4-ethynylphenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo^2,2,2^octane
ORIGINAL 4
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j. .. i
- 7 P16
By the term hydrocarbyl group is meant alkyl, alkenyl (including cyclic alkyl and alkenyl, and alkyl and alkenyl substituted by cyclic alkyl and alkenyl), alkynyl, aryl and aralkyl groups. Hydrocarbyloxy means a hydrocarbyl group as defined where linked to oxygen.
In a further aspect, the present invention provides a process for the preparation of a compound of the formula (I). The process for the preparation of a compound of the formula (I) may be any method known in the art for preparing analogous compounds, for example :
‘Ί* 10 (i) by the reaction of the corresponding compound which contains iodo in place of -CxC-R^ with a compound HC^CR'’ wherein R^ is as hereinbefore defined. This reaction is carried out in the presence of a suitable palladium catalyst well known to those skilled in the art for this type of reaction, for example bis15 triphenylphosphine palladium dichloride, and a catalytic amount of a cuprous halide, such as cuprous iodide. The reaction will normally be carried out in the presence of basic solvent such as diethylamine or triethylamine at a non-extreme temperature, for example between -50°and 100°C and conveniently at room temperature. The starting material, i.e. the iodophenylbicycloalkane, wherein V 20 and are oxygen and Z is CR^O may be prepared by the cyclisation of a compound of the formula (II) ;
3 2x wherein R, R and R are as hereinbefore defined and R is an iodo substituted phenyl group, in the presence of an acid catalyst. Boron trifluoride etherate is a particularly preferred acid catalyst for this cyclisation which will normally be carried out in an inert solvent, such as a halogenated hydrocarbon, conveniently dichloromethane, at below ambient temperature, for example between -100 and
0°C and conveniently between -70 and -50°C
BAD ORIGINAL C
AJR/EB/2.9.86
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The compounds of the formula (II) may be prepared by the reaction of compounds of the formula (III) and (IV):
(III) r2x-c(=o)l (IV) where is a group and R, r\ R^x and are as hereinbefore defined and
L is leaving group such as halo. This reaction conveniently takes place in an inert solvent in the presence of base at a non-extreme temperature. Halogenated hydrocarbons, such as dichloromethane are particularly suitable solvents, pyridine is a preferred base and the reaction will conveniently be carried out at between -50 and 100°C, preferably at 0°C.
AP 0 0 0 0 6 5
The compounds of the formula (III) may in turn be prepared from compounds of the formula (V):
wherein R, and R^ are as defined above and Y and are oxygen and Z is CH^OH, by reaction with diethyl carbonate in the presence of a strong base, for example potassium hydroxide, in a polar solvent, such as an alcohol, for example ethanol, at an elevated temperature, for example between 50 and 100°C. This is a preferred method of making compounds of the formula (III) wherein
R1=R14=CF.
» -/
The compounds of the formula (III) may alternatively be prepared by the reaction of a Grignard reagent R^MgHal with a compound of the formula (VI)
AJR/EB/2.9.86
ORIGINAL ft
- 9 P16
ο ©
© jQ wherein R, and R^ are as hereinbefore defined and Hal is a halogen atom such as bromine or iodine. This reaction is conveniently carried out in an inert solvent, suitably an ether for example diethyl ether, at a non-extreme temperature, for example between -50 and 50°C and preferably between -10° and 10°C. The compounds of the formula (VI) may be prepared by oxidation of compounds of the formula (III) wherein R^ is hydrogen by using oxalyl chloride and dimethyl sulphoxide in an inert solvent, such as a halogenated hydrocarbon, for example dichloromethane, followed by a base such as triethylamine or by using pyridinium chlorochromate in an inert solvent, such as a halogenated hydrocarbon, for example dichloromethane.
The compounds of the formula (III) wherein R^ is hydrogen may be prepared from compounds of formula (V) in an analogous manner to the preparation of the compounds of the formula (III) where R is trifluoromethyl.
The triol of the formula (V) may be prepared :
(i) In certain cases, it may be convenient to prepare triol derivatives where r\ r3 are hydrogen and one of the hydroxy groups is protected, by reduction of an ester of the formula (VII):
(VII) wherein R^ is a hydroxy protecting group such as benzyl and R^ is alkyl. This reduction is suitably carried out by a complex hydride such as lithium aluminium hydride in an inert solvent conveniently an ether. The
AJR/EB/2.9.86 />
< /»·
riginal
- 10 P16 compound of the formula (VII) may be prepared from the corresponding compound RCHCCO^R^)^ by reaction with a compound XCh^OR^, wherein X is a leaving group such as a halogen, in the presence of a strong base, such as sodium hydride.
(ii) when it is required to prepare a compound of the formula (I) wherein R^ is hydrogen, by the reduction of a compound of the formula (VIII):
(VIII) wherein R, R^ and R^ are as hereinbefore defined. This reduction is suitably carried out by means of a complex hydride, such as lithium aluminium hydride in an inert solvent such as an ether, for example diethyl ether.
When R and R^ are linked to form a carbocyclic ring, the compound of the formula (VIII) is conveniently prepared by the reaction of a compound of the formula (IX)
(IX) with a compound hal-CO2R16> wherein R, R1 and Ri6 are as hereinbefore defined and hal is halogen, for example chlorine. This reaction is conveniently ^ADjORIGINAL
AJR/EB/2.9.86
- 11 P16 carried out in the presence of a Grignard reagent for example ethyl magnesium bromide, in an inert solvent such as an ether, for example tetrahydrofuran. Other compounds of the formula (VIII) are conveniently prepared by the reaction of a compound RCF-KCC^R^^ with a compound hal CO.R^ wherein R, r\ R^ and hal are as hereinbefore defined or trifluoroacetic anhydride. This reaction is conveniently carried out in the presence of a strong base, such as a metal hydride in a non-polar solvent, for example an aromatic hydrocarbon such as benzene or toluene.
The compounds which contain iodo in place of -C=C-R^ may also be prepared V from the corresponding bromo compound. This reaction proceeds by the reaction of the bromo compound with an alkyllithium compound, for example nbutyllithium, in an inert solvent, such as an ether, conveniently diethyl ether, at y a non-extreme temperature, for example between -80* and 20 *C and conveniently between -70 and O’C, to give the corresponding lithium intermediate which is then reacted with iodine in an inert solvent such as an ether, conveniently diethyl ether. The reaction sequence is conveniently carried out in situ, the organo lithium intermediate not being isolated.
The bromo-compound may be prepared by the cyclisation of a compound of the formula (II) wherein R is a bromosubstituted phenyl group under the conditions previously described for the corresponding iodo compound. Alternatively, it may be prepared by the reaction of a compound analogous to that of the formula (V) and wherein R, r\ R”\ Y, Y^ and Z are as defined in relation to formula (I) with 2x 17 2k an orthocarboxylate of the formula R C(OR ), wherein R is a ? bromosubstituted phenyl group and R is C, . alkyl, phenyl or C, aralkyl. Suitably R is methyl or ethyl, preferably methyl. The reaction is normally carried out in the presence of an acid such as a mineral acid, conveniently hydrochloric acid or a sulphonic and derivative, such as toluene sulphonic acid, or an acid resin, or in the presence of a trialkylamine, such as triethylamine, at an elevated temperature, for example between 50 and 200 *C, conveniently between 120 and 170 *C. The reaction may conveniently be carried out in the absence of a solvent but a suitable solvent may be added if desired. The preparation of such bromophenylsubstituted bicyclooctanes is described in published
European Patent Appln. No. 152229 and in our copending Applns·
No. AP/P/86/00038 and one filed simultaneously herewith, which are incorporated by reference herein.
(ii) The compounds of the formula (I) wherein R^ is hydrogen may also be prepared by dehydrobromination of the corresponding 1,2-bromoethyl compound,
BAD ORIGINAL
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i.e. a compound wherein fv is replaced by a (l,2-bromoethyl)phenyl group. This reaction is conveniently carried out in the presence of sodamide in liquid ammonia. The reaction may be carried out in an inert solvent, such as an ether, for example tetrahydrofuran at a non-extreme temperature, for example between -20 and 50 *C and conveniently at room temperature.
(iii) It is often convenient to prepare compounds of the formula (I) by interconversion from other compounds of the formula (I), for example:
(i): when it is desired to prepare a compound of the formula (I) wherein R^ is other than hydrogen by the reaction of the corresponding compound wherein R^ is hydrogen with a compound Hal R^ wherein hal is halogen and
R^ is other than hydrogen. This reaction is particularly suitable for the preparation of those compounds wherein R^ is a C. . alkyl group or a 6 6 group COR wherein R is a C^ alkoxy group. The reaction is normally carried out in the presence of a strong base, such as an alkyllithium conveniently butyllithium in an inert solvent, such as an ether, for example tetrahydrofuran, at a non-extreme temperature, for example between -50° and 50°C and conveniently between -10 and 30°C. The starting material,
i.e. the unsubstituted alkynylphenyl bicycloalkane may be prepared as described above.
s 9 0 0 0 0 dV (ii) when it is desired to prepare a compound of the formula (I) wherein R^ is hydrogen by the desilylation of a compound of the formula (I) wherein R^ is a tri-C^ alkylsilyI group. This reaction may be carried out by methods well known to those skilled in the art, for example by reaction with tetrabutyl-ammonium fluoride in an ether, such as tetrahydrofuran, at a non-extreme temperature, for example between 0* and 70 *C and conveniently at room temperature.
The compounds of Formula (I) may be used to control arthropods such as insect and acarine pests. Thus, the present invention provides a method for the control of arthropods which comprises administering to the arthropod or to its envirtjnment on arthropodically effective amount of a compound of the formula (I). The present invention also provides a method for the control and/or eradication of arthropod infestations on animals (including humans) which comprises administering to the animal an effective amount of a compound of the formula (I). The present invention further provides for the compounds of the
AJR/EB/2.9.86
BAD ORIGINAL
- 13 P16 formula (I) for use in human and veterinary medicine for the control of arthropod pests.
The compounds of Formula (I) may be used for such purposes by application of the compounds themselves or in diluted form in known fashion as a dip, spray, lacquer, foam, dust, powder, aqueous suspension, paste, gel, shampoo, grease, combustible solid, vapourising mat, combustible coil, bait, wettable powder, granule, aerosol, emulsifiable concentrate, oil suspensions, oil solutions, pressure-pack, impregnated article or pour on formulation. Dip concentrates are not applied per se, but diluted with water and the animals immersed in a dipping bath containing the dip wash. Sprays may be applied by hand or by means of a spray race or arch. The animal, plant or surface being treated may be saturated with the spray by means of high volume application or superficially coated with the spray by means of light or ultra low volume application. Aqueous suspensions may be applied in the same manner as sprays or dips. Dusts may be distributed by means of a powder applicator or, in the case of animals, incorporated in perforated bags attached to trees or rubbing bars. Pastes, shampoos and greases may be applied manually or distributed over the surface of an inert materia] against which animals rub and transfer the material to their skins. Pour-on formulations are dispensed as a unit of liquid of small volume on to the backs of animals such that all or most of the liquid is retained on the animals.
The compounds of Formula (I) may be formulated either as formulations ready for use on the animals, plants or surface or as formulations requiring dilution prior to application, but both types of formulation comprise a compound of Formula (I) in intimate admixture with one or more carriers or diluents. The carriers may be liquid, soiid or gaseous or comprise mixtures of such substances, and the compound of Formula (I) may be present in a concentration of from 0.025 to 99% w/v depending upon whether the formulation requires further dilution.
Dusts, powder and granules comprise the compound of Formula (I) in intimate admixture with a powdered solid inert carrier for example suitable clays, kaolin, talc, mica, chalk, gypsum, vegetable carriers, starch and diatomaceous earths.
Sprhys of a compound of Formula (I) may comprise a solution in an organic solvent (e.g. those listed below) or an emulsion in water (dip wash or spray wash) prepared in the field from an emulsifiable concentrate (otherwise known as a water miscible oil) which may also be used for dipping purposes. The concentrate preferably comprises a mixture of the active ingredient, with or without an
AJR/EB/2.9.86 bad original d
- 14 PI6 organic solvent and one or more emulsifiers. Solvents may be present within wide limits but preferably in an amount of from 0 to 90% w/v of the composition and may be selected from kerosene, ketones, alcohols, xylene, aromatic naphtha, and other solvents known in the formulating art. The concentration of emulsifiers may be varied within wide limits but is preferably in the range of 5 to 25 % w/v and the emulsifiers are conveniently non-ionic surface active agents including polyoxyalkylene esters of alkyl phenols and polyoxyethylene derivatives of hexitol anhydrides and anionic surface active agents including Na lauryl sulphate, fatty alcohol ether sulphates, Na and Ca salts of alkyl aryl sulphonates and alkyl sulphosuccinates.
co
Wettable powders comprise an inert solid carrier, one or more surface active agents, and optionally stabilisers and/or anti-oxidants.
Emulsifiable concentrates comprise emulsifying agents, and often an organic solvent, such as kerosene, ketones, alcohols, xylenes, aromatic naphtha, and other solvents known in the art.
Wettable powders and emulsifiable concentrates will normally contain from 5 to 20 95% by weight of the active ingredient, and are diluted, for example with water, before use.
Lacquers comprise a solution of the active ingredient in an organic solvent, together with a resin, and optionally a plasticiser.
Dip washes may be prepared not only from emulsifiable concentrates but also from wettable powders, soap based dips and aqueous suspensions comprising a compound of Formula (I) in intimate admixture with a dispersing agent and one or more surface active agents.
Aqueous suspensions of a compound of Formula (I) may comprise a suspension in water together with suspending, stabilizing or other agents. The suspensions or solutions may be applied per se or in a diluted form in known fashion.
Greases (or ointments) may be prepared from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base such as soft paraffin. A compound of Formula (I) is preferably distributed uniformly through the mixture in solution or suspension. Greases may also be made from emulsifiable concentrates by diluting them with an ointment base.
bad original
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Pastes and shampoos are also semi-solid preparations in which a compound of Formula (I) may be present as an uniform dispersion in a suitable base such as soft or liquid paraffin or made on a non-greasy basis with glycerin, mucilage or a suitable soap. As greases, shampoos and pastes are usually applied without further dilution they should contain the appropriate percentage of the compound of Formuia (I) required for treatment.
Aerosol sprays may be prepared as a simple solution of the active ingredient in the aerosol propellant and co-solvent such as halogenated alkanes and the r-jj)o solvents referred to above, respectively. Pour-on formulations may be made as a solution or suspension of a compound of Formula (I) in a liquid medium. An '' avian or mammal host may also be protected against infestation of acarine ectoparasites by means of carrying a suitably-moulded, shaped plastics article v impregnated with a compound of Formula (I). Such articles include impregnated collars, tags, bands, sheets and strips suitably attached to appropriate parts of the body. Suitably the plastics material is a polyvinyl chloride (PVC).
The concentration of the compound of Formula (I) to be applied to an animal will vary according to the compound chosen, the interval between treatments, the nature of the formulation and the likely infestation, but in general 0.001 to
20.0% w/v and preferably 0.01 to 10% of the compound should be present in the applied formulation. The amount of the compound deposited on an animal will vary according to the method of application, size of the animal, concentration of the compound in the applied formulation, factor by which the formulation is diluted and the nature of the formulation but in general will lie in the range of from 0.0001% to 0.5% except for undiluted formulations such as pour-on formulations which in general will be deposited at a concentration in the range from 0.1 to 20.0% and preferably 0.1 to 10%.
The compounds of formula (I) are also of use in the protection and treatment of plant species, in which case an effective insecticidal or acaricidal amount of the active ingredient is applied. The application rate will vary according to the compound chosen, the nature of the formulation, the mode of application, the plant species, the planting density and likely infestation and other like factors but ih general, a suitable use rate for agricultural crops is in the range 0.001 to
3kg/Ha and preferably between 0.01 and lkg/Ha. Typical formulations for agricultural use contain between 0.0001% and 50% of a compound of formula (I) and conveniently between 0.1 and 15% by weight of a compound of the formula (I).
BAD ORIGINAL
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Particular crops include cotton, wheat, maize, rice, sorghum, soya, vines, tomatoes, potatoes, fruit trees and spruce.
Dusts, greases, pastes and aerosol formulations are usually applied in a random fashion as described above and concentrations of 0.001 to 20% w/v of a compound of Formula (I) in the applied formulation may be used.
The compounds of formula (I) have been found to have activity against the common housefly (Musca domestica). In addition, certain compounds of formula (I) have activity against other arthropod pests including Tetranychus urticae Plutella xylostella, Culex spp. and Blattella qermanica) The compounds of formula (I) are thus useful in the control of arthropods e.g. insects and acarines in any environment where these constitute pests, e.g. in agriculture, in animal husbandry, in public health control and in domestic situations.
Insect pests include members of the orders Coleoptera (e.g. Anobium, Tribolium, Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), Lepidoptera (e.g. Fphestia, Plutella, Chilo, Heliothis, Spodoptera or Tineola spp.), Diptera (e.g. Musca, Aedes, Culex, Glossina, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomia, Callitroqa, Dermatobia, Hypoderma, Liriomyza and Melophaqus spp.), Phthiraptera (Malophaqa e.g. Damalina spp. and Anoplura e.g. Linoqnathus and Haematopinus spp.), Hemiptera (e.g. Aphis, Bemisia, Aleurodes, Nilopavata, Nephrotetix or Cimex spp.), Orthoptera (e.g. Schistocerca or Acheta spp.), Dictyoptera (e.g. Blattella, Periplaneta or Blatta spp.), Hymenoptera (e.g. Solenopsis or Monomorium spp.), Isoptera (e.g. Reticulitermes spp.), Siphonaptera (e.g. Ctenocephalides or Pulex spp.), Thysanura (e.g. Lepisma spp.), Dermaptera (e.g. Forficula spp.) and Pscoptera (e.g. Peripsocus spp.).
Acarine pests include ticks, e.g. members of the genera Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermocentor and Anocentor, and mites and manges such as T etranychus, Psoroptes, Notoednes, Psorerqates, Chorioptes and Demodex spp.
Corflpounds of the invention may be combined with one or more other active ingredients (for example pyrethroids, carbamates and organophosphates) and/or with attractants and the like. Furthermore, it has been found that the activity of the compounds of the invention may be enhanced by the addition of a synergist or potentiator, for example: one of the oxidase inhibitor class of
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- 17 P16 synergists, such as piperonyl butoxide or propyl 2-propynylphenylphosphonate; a second compound of the invention; or a pyrethroid pesticidal compound. When an oxidase inhibitor synergist is present in a formula of the invention, the ratio of synergist to compound of Formula (I) will be in the range 25:1-1:25 eg about
10:1.
Stabilisers for preventing any chemical degradation which may occur with the compounds of the invention include, for example, antioxidants (such as tocopherols, butylhydroxyanisole and butylhydroxytoluene) and scavengers (such as epichlorhydrin) and organic or inorganic bases e.g. trialkylamines such as triethylamine which can act as basic stabilisefc’and as scavengers.
Λ
O
The following Examples illustrate, in a non-limiting manner, preferred aspects of >15 the invention. All temperatures are in degrees Celsius.
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Example 1
4-Ethyl-l-[4-(2-trimethylsilylethynyl)-phenylj-2,6,7-trioxabicyclo(2,2,2]octane (i) A mixture of 2-ethyl-2-hydroxymethyl-propan-l,3-diol(13.4gms) (prepared in an anologous method to 2-n-propyl-2-hydroxymethyl-propan-l,3-diol (Ex.3(i)), diethyl carbonate (12.3ml), potassium hydroxide (O.lgm) and dry ethanol (lml)was heated to gentle reflux (oil bath 110-120°) under a stream of nitrogen for 30 minutes. After this time the ethanol formed was removed by distillation at atmospheric pressure (oil bath 130 - 140°, still head temperature <76°). The pressure was reduced to 20 mm Hg and the oil bath temperature adjusted to 230°. 3-ethyl-3hydroxymethyloxetane distilled as a colourless liquid (9.1g., head temperature 150°).
Gas-liquid chromatography (g.l.c.) : OV-210 at 100° produced one peak. Nuclear magnetic resonance spectrum (N.M.R.) was as follows : ^H(ppm from TMS in CDCl^,integral, multiplicity, JHz): 4.40, 4H, s; 3.70, 2H, m; 1.7, 2H, q, 8; 0.9, 3H, t, 8.
(ii) A solution of 4-iodobenzoyl chloride (11.5 gms) in dry ether (50ml) was added to a stirred solution of 3-ethyl-3-hydroxymethyloxetane (5 gms) and pyridine (3.5mls) in ether (100 ml) at 0°C. The resulting mixture was allowed to warm to room temperature and stirred for 24 hours. After this time the mixture was washed with water and brine. The organic extracts were dried over anhydrous magnesium sulphate and then evaporated in vacuo. The residue was purified by column chromatography on silica (preeluted with 1% triethylamine in hexane) and eluted with 5% ethyl acetate in hexane. 3-Ethyl-3-(4-iodobenzoyloxymethyl) oxetane was obtained as a colourless oil (8.1 gms).
Nuclear magnetic resonance spectrum (N.M.R.) was as follows : (ppm from TMS in CDCly integral, multiplicity JHz): 7.60, 4H, s; 4.60-4.35, 6H, m; 1.8, 2H, q, 8; 0.95, 3H, q, 8.
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- 19 P16 (:ii) Boron trifluoride etherate (0.44 ml) was added to a stirred solution of 3ethyl-3-(4-iodobenzoyloxymethyl-oxetane 4.9 gms) in dry dichloromethane (30ml) at -70° under nitrogen. The resulting mixture was allowed to warm to room temperature and then stirred for 20 hours. After this time triethylamine (2mls) was added. The reaction mixture was washed with water and the organic layer was dried over anhydrous potassium carbonate and then evaporated jn vacuo. The residue was purified by chromatography on alumina, eluting with 40% hexane in dichloromethane saturated with ammonia. 4-Ethyl-l-(4-iodophenyl)-2,6,710 trioxabicyclo[2,2,2]octane was obtained as a white solid (2.9gms).
··© © Gas-liquid chromatography (g.l.c.) : OV-210 at 230° produced one peak.
O \ Nuclear magnetic resonance spectrum (N.M.R.) was as follows : (ppm *
from TMS in CDCl^, integral, multiplicity, JHz) :
7.60, 2H, d, Θ; 7.30, 2H, d, 8; 4.05, 6H, s; 1.5-0.7, 5H, m.
(iv) Bis-triphenylphosphine palladium dichloride (60mg) and cuprous iodide (lOmg) were added to a stirred solution of 4-ethyl-l-(4-iodophenyl)-2,6,7trioxabicyclo[2,2,2]octane (1.5gms) and trimethylsilylacetylene (0.92ml) in dry diethylamine (40 mi) under nitrogen. The resulting mixture was stirred at room temperature for 16 hours. After this time the solvent was removed under vacuum and the residue extracted with diethylether. The ethereal solution was washed with water, dried over anhydrous magnesium sulphate and evaporated m vacuo. The residue was purified by column chromatography on alumina, eluting with 30% dichloromethane in hexane saturated with ammonia. 4-Ethyi-l-[4-(2-trimethylsilylethynyl)-phenyl]2,6,7-trioxabicyclo[2,2,2]octane (1.2 gms) was obtained as an off-white solid (1.2gms) after recrystallisation from hexane.
Gas liquid chromatography (g.l.c.): OV-210 at 230° produced one peak.
Using the methodology described above starting with the appropriate aryl iodide and trimethylsilylacetylene, the following compounds were prepared :4-ethyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane
4-n-propyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2Joctane
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4-n-butyl-l-(4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane
4-t_-butyl-l-[4-(2-trimethyIsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,21octane
4-t-butyl-l-[3-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicycio[2,2,2]octane
4-i-butyl-l-(4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane
4-n-pentyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane l-[3-chloro-4-(2-trimethylsilylethynyI)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane l-[3-nitro-4-(2-trimethylsilyIethynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
4-phenyl-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2)octane
4-cyclohexyl-l-(4-(2-trimethylsilylethynyl)phenyl-2,6,7-trioxabicyclo[2,2,2]octane
The 3-chloro-4-iodobenzoic acid and 3-nitro-4-iodobenzoic acid starting materials were prepared by the method of Hodgson and Beard (J.Chem.Soc., 1927,20).
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Example 2
Ethyl 3-[4-(4-ethyl-2!6>7-trioxabicyclo[2)2,2]oct-l-yl)phenyl]prop-2-ynoate.
(i) Tetrabutyl ammonium fluoride solution (3.3ml,lM in tetrahydroforan) was added to a stirred solution of 4-ethyl-l-[4-(2-trimethyIsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane (0.87gms) in tetrahydrofuran (15ml). The mixture was stirred for 30 minutes at room temperature when the solvent was removed under vacuum. The residue was taken up in ether and washed with water and brine. The ethereal solution was dried over anhydrous magnesium sulphate and evaporated jn vacuo. Recrystallisation from hexane gave 4-ethyl-l-(4-ethynylphenyl)-2,6,7trioxabicyclo[2,2,2]octane as an off-white solid (0.66gms).
Gas-liquid chromatography (g.l.c.): OV-210 at 230° produced one peak.
Nuclear magnetic resonance spectrum (N.M.R.) was as follows : (ppm from TMS in CDClyintegral, multiplicity);
7.50, 4H, m; 4.1, 6H, s; 3.1, 1H, s; 1.6-0.7, 5H, m.
(ii) n-Butyl lithium solution (0.67ml, 1.6M in hexane) was added to a stirred solution of 4-ethyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo(2,2,2)octane (200mg) in tetrahydrofuran (5ml) at 0°C under nitrogen. The solution was
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- 21 P16 maintained at 0°C for 10 minutes when ethyl chloroformate (0.1ml) was added neat. The solution was allowed to warm to room temperature over
1.5 hours. The reaction was quenched with water (1 ml) and the solvent was removed under vacuum. The residue was taken up in ether and washed with water and brine. The ethereal solution was dried over anhydrous 5 magnesium sulphate and then evaporated jn vacuo. The residue was extracted with boiling hexane and afforded ethyl 3-[4-(4-ethyl-2,6,7trioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynoate (67 mg) as an off-white t
crystalline solid on cooling.
Mu*
O 10 Gas-liquid chromatography (g.l.c.) : OV-17 at 230° produced one peak.
Using the methodology described in (i) above, starting from the appropriate trimethylsilyiethynyl analogues prepared in example 1, the following compounds were prepared :15
4-ethyl-l-(4-ethynyiphenyl)-2,6,7-trioxabicyclo(2,2,2)octane l-(4-ethynyIphenyl)-4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octane 4-n-butyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo(2,2,2]octane 4-l·butyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane l-(4-ethynyiphenyl)-4-n-pentyl-2,6,7-trioxabicyclo[2,2,2]octane
4-(2,2-di-methylpropyl)-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane l-(3-chloro-4-ethynyiphenyI)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane l-(4-ethynyl-3-nitrophenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane 4-phenyl-l-(4-ethynylphenyl)-2,6,7-trioxabicycl o[2,2,2] octane
4-_t-butyl-l-(3-ethynylphenyl)-2,6,7-trioxabicyclo(2,2,2]octane
4-_t-butyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo(2,2,2]octane
Using the methodology described in (ii) above and starting from 1-(4ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octane and methyl chloroformate, methyl 3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-lyl)phenyl]prop-2-ynoate was prepared.
*
The nmr data for these products is provided in the table other than for 4-^-butyll-(3-ethynylphenyI)-2,6,7-trioxabicyclo[2,2,2]octane which gave the following
NMR spectrum : (ppm from TMS in CDCl^, integral, number of peaks):
7.75-7.20,4H,m; 4.15,6H,s; 3.0,lH,s; 0.90,9H,s.
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Example 3
1-(^-(3-Met ho xyprop-l-ynyl)phenyl]-4-propy 1-2,6,7-trioxabicyclo[2,2,2]octane (i) To a stirred mixture of n-valeraldehyde (172g) and water (2 J.) was added solid calcium hydroxide (112g.) and formaldehyde solution (1.4 1. of 40% aqueous solution). The reaction temperature was maintained below 40* and the addition took about 45 minutes. The mixture was then maintained at 60 * for 5 hours. The reaction mixture was filtered through Kieselguhr and the filtrates were evaporated jn vacuo. The residue was treated with hot methanol (2 1.) and the mixture was filtered through Kieselguhr. The filtrates were evaporated in vacuo. A viscous oily product was obtained (458 g.) and was purified as follows :15
A solution of the crude product and acetic acid (200 mi.) was stirred at room temperature. Acetic anhydride (1.2 1.) was added over 4 hours. The temperature rose to 65*. Stirring was continued for 12 hours. The reaction mixture was added over 5 hours to cold water (3 1.) with stirring. Stirring was continued for 3 hours. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with aqueous sodium hydrogen carbonate solution and then with brine. The extracts were dried over anhydrous magnesium sulphate and then evaporated in vacuo.
S u M Mu MdV
Distillation gave 2-n-propyl-2-hydroxymethyl-propan-l,3-diol triacetate (238 g.), a colourless oil (b.pt. 120-140*, 1.5 mm).
Nuclear magnetic resonance spectrum (NMR) was as follows : ·*Ή (ppm from TMS in CDClp integral, number of peaks):
4.00, 6H, s; 2.10, 9H, s; 1.40, 4H, m; 1.00, 3H, m.
Sodium (0.5g.) was added to a stirred solution of the above triacetate (238g.) in methanol (2.5 1.). The mixture was refluxed, with stirring, for 72 hours. The mixture was evaporated i_n vacuo.
2-n-Propyl-2-hydroxymethyl-propan-l,3-diol (87 g.) was obtained as colourless crystals (m.pt. 93 ·).
ref. W.E.Conrad, L.A.Levasseur, R.F.Murphy, N.L.Hare and H.E. Conrad.
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Example 3 l-(4-(3-Methoxyprop-l-ynyl)phenyl]-4-propyl-2,6,7-trioxabicyclo[2,2,2]octane (i) To a stirred mixture of n-valeraldehyde (172g) and water (2 1.) was added solid calcium hydroxide (112g.) and formaldehyde solution (1.4 1. of 40% aqueous solution). The reaction temperature was maintained below 40* and the addition took about 45 minutes. The mixture was then maintained at 60* for 5 hours. The reaction mixture was filtered through Kieselguhr > and the filtrates were evaporated jn vacuo. The residue was treated with ^10 hot methanol (2 1.) and the mixture was filtered through Kieselguhr. The filtrates were evaporated in vacuo. A viscous oily product was obtained , (458 g.) and was purified as follows :-g
A solution of the crude product and acetic acid (200 ml.) was stirred at 15 room temperature. Acetic anhydride (1.2 1.) was added over 4 hours. The temperature rose to 65*. Stirring was continued for 12 hours. The reaction mixture was added over 3 hours to cold water (3 1.) with stirring.
Stirring was continued for 3 hours. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with aqueous sodium hydrogen carbonate solution and then with brine. The extracts were dried over anhydrous magnesium sulphate and then evaporated in vacuo.
Distillation gave 2-n-propyl-2-hydroxymethyl-propan-l,3-diol triacetate (238 g.), a colourless oil (b.pt. 120-140*, 1.5 mm).
25 1
Nuclear magnetic resonance spectrum (NMR.) was as follows : H (ppm from TMS in CDCly integral, number of peaks):
4.00, 6H, s; 2.10, 9H, s; 1.40, 4H, m; 1.00, 3H, m.
Sodium (0.5g.) was added to a stirred solution of the above triacetate (238g.) in methanol (2.5 1.). The mixture was refluxed, with stirring, for 72 hours. The mixture was evaporated in vacuo.
2-n-Propyl-2-hydroxymethyl-propan-l,3-diol (87 g.) was obtained as colourless crystals (m.pt. 93*).
ref. W.E.Conrad, L.A.Levasseur, R.E.Murphy, N.L.Hare and H.E. Conrad.
_bad original 0'
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- 24 P16 extracted with diethyl ether. The ethereal solution was washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
The residue was purified by column chromatography on alumina, eluting with 30% dichloromethane in hexane saturated with ammonia. 1-(4-(3Methoxyprop-l-ynyl)phenyI]-4-propyl-2,6,7-trioxabicyclo[2,2,2)octane was obtained as an off-white solid (67mg) after recrystallisation from hexane.
Gas-liquid chromatography (g.l.c.) : OV-17 at 240°produced one peak.
In an analogous manner the following compounds were prepared from 1-(4iodophenyl)-4-propyl-2,6,7-trioxabicyclo[2,2,2] octane and the respective acetylene components (which are indicated in brackets) :
4-propyl-l-[4-(2-tri methylsilylethynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2] octane, (trimethylsiiylacetylene).
3- (4-(4-propyl-2,6,7-trioxabicyclo[2,2,2]octyi)phenyl]-prop-2-yn-l-ol.
(propargyl alcohol).
l-(4-(2-phenylethynyl)phenyl]-4-propyl-2,6,7-trioxabicyclo[2,2,2)octane (phenylacetylene).
l,l-dimethyl-3-[4-(4-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynl-ol.
(l,l-dimethylprop-2-yn-l-ol)
4- (4-(4-propyl-2,6,7-trioxabicyclo[2,2,2]octyl)phenyl]but-3-yn-l-ol.
(but-3-yn-l-ol) l-(4-(2-_t-butylethynyl)phenyl]-4-propyl-2,6,7-trioxabicyclo(2,2,2]octane (3,3-dimethylbut-l-yne))
In an analogous manner the following compounds were prepared from the ' appropriate l-(4-iodophenyl)-4-substituted-2,6,7-trioxabicyclo(2,2,2Joctane and the respective acetylene component (which is indicated in brackets in each case).
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>
4-t-butyl-l-[4-(3-metboxyprop-l-ynyl)phenyl]-2,6,7-trioxabicyclo(2,2,2]octane (methyl propargyl ether) l-[3-chloro-4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane (methyl propargyl ether)
4-cyclohexyl-l-[4-(3-methoxyprop-l-ynyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane (methyl propargyl ether) l_[4-(3-ethoxyprop-l-ynyl)phenyl]4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane (ethyl propargyl ether)
4-methoxy-l-[4-(4-n-propyl-2,6,7-trioxabicyclo(2,2,2]oct-l-yl)phenyl]but-l-yne (4-methoxybut-l-yne)
4-j-butyl-l-[4-(3-methoxyprop-l-ynyl)phenyl]-2.6.7-trioxabicyclo[2,2,2]octane (methyl propargyl ether)
N-[3-[4-(4-n-propyl-2,6,7-trioxabicyclo(2,2,2]oct-l-yl)phenyl]prop-2-ynyl]acetamide (N-prop'2-ynyl acetamide - Chem.Abs., 54; 3178h)
4-n-butyl-l-[4-(3-methoxyprop-l-ynyl)phenyi]-2,6,7-trioxabicycIo[2,2,2]octane (methyl propargyl ether) l-(4-(3-methoxyprop-l-ynyl)phenyl]-4-n-pentyl-2,6,7-trioxabicyclo[2,2,2]octane (methyl propargyl ether) l-[4-(pent-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octane (pent-l-yne)
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Example 4 l-[4-(3-Methoxyprop-l-ynyl)phenyl]-4-n-propyl-3-trifluoromethyl-2,6,7trioxabicyclo[2,2,2]octane (i) Sodium hydride (8.0g 60% dispersion in oil) was added to a stirred solution of diethyl n-propylmalonate (40g.) in dry benzene (200 ml.). The mixture was maintained at 60*, with stirring, for 1 hour. The mixture was cooled and trifluoracetic anhydride (28ml.) was added carefully. The mixture
1θ was stirred at room temperature for 2 hours. Water was added and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
Distillation gave diethyl 2-n-propyl-2-trifluoroacetyImalonate, a colourless oil (b.pt, 73*, 0.2m.m.)(35g.).
Gas-liquid chromatography (g.l.c.) : OV 210 at 130 * produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TM5 in CDCl-j, integral, number of peaks, J^z
AP 0 0 0 0 6 5
4.30, 4H, q, 8; 2.00, 2H, m; 1.50 - 0.70, 11H, m.
(ii) Lithium aluminium hydride (5.5g.) in dry diethyl ether (200 ml.) was stirred at 0 · under a current of nitrogen. Diethyl 2-n-propyI-2trifluoroacetyl-malonate (25.Og.) in dry diethyl ether (50 ml) was added and the mixture was stirred at room temperature for 3 hours. The mixture was then refluxed, with stirring, for 4 hours. The mixture was cooled and a solution of sodium hydroxide (20 g.) and potassium hydrogen phosphate (20g.) in water (150 ml.) was added carefully. The solid was filtered off and air-dried. The filtrates were evaporated to dryness in vacuo. All the solids were combined and extracted with hot chloroform , for 48 hours (soxhlet extraction). The extracts were evaporated in vacuo.
3,3-Di-(hydroxymethyl)-l,l,l-trifluorohexan-2-ol was obtained as a yellow viscous oil (11.0 g.) and was used without further purification.
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Infrared spectrum (1R) liquid film:
3340 (strong and broad), 1155(s), 1100(s), 1040(m), 1020(m).
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCl^, integral, number of peaks):
4.20, 1H, m; 4.00-3.10, 7H, m; 1.30, 4H, m; 0.90, 3H, m.
M
O o
o .0 (iii) A mixture of 3,3-di-(hydroxymethyl)-l,l,l-trifluorohexan-2-ol (2.8g.), diethyl carbonate (1.6ml.), potassium hydroxide (O.lg) and dry ethanol (4.0 mis) was refluxed gently (oil bath 110°), under a current of nitrogen, for 30 minutes. The ethanol was then removed by distillation. Distillation gave 3-(l-hydroxy-2,2,2-trifluoroethyl)-3-n-propyloxetane (1.7g.), a colourless oil (b.p. 112°, 20-25 m.m.).
Gas-liquid chromatography (g.l.c.) : OV 210 at 120° produced one peak.
Infrared spectrum (1R) (liquid film) :
3450 (s,br), 1300 (s), 1170(s), 1130(s), 1045 (s).
(iv) A solution of 4-iodobenzoyl chloride (2.1g.) in dry dichloromethane (25mls) was added to a stirred solution of 3-(l-hydroxy-2,2,2-trifluoroethyl)-3-npropyl-oxetane (1.55g.) and pyridine (1.0ml.) in dry dichloromethane, at 0°. The reaction mixture was stirred for 24 hours, at room temperature.
3q The mixture was poured into water and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
. The residue was purified by column chromatography on silica, eluting with 1% triethylamine in hexane.
3_[l-(4-Iodobenzoyloxy)-2,2,2-trifluoroethyl)-3-n-propyloxetane was obtained as a colourless oil (2.4g.).
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Gas-liquid chromatography (g.l.c.) : OV 210 at 200° produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCl-j, integral, number of peaks) :
7.70, 4H, m; 4.80 - 4.20, 5H, m; 2.20 - 0.80, 7H, m.
(v) Boron trifluoride etherate (0.54ml.) was added to a stirred solution of 3(l-(4-iodobenzoyloxy)-2,2,2-trifluoroethyl]-3-n-propyloxetane (2.3g.) in dry dichloromethane (50mls.) at -70°. The mixture was allowed to warm up slowly to room temperature and was then stirred for 12 hours. Triethylamine (1.0ml.) was added and the mixture was poured into water.
The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on alumina eluting with 1 : 4 dichloromethane : hexane saturated with ammonia.
l-(4-Iodophenyl)-4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo(2,2,2]octane was obtained as a colourless solid (0.53g.).
Gas-liquid chromatography (g.l.c.) : OV210 at 220° produced one peak.
Nuclear magnetic resonance spectrum (N.M.R.) was as follows : (ppm from TMS in CDCl^, integral, number of peaks, J^z) ·
7.70, 2H, d, 8; 7.30, 2H, d, 8; 4.80 - 3.80, 5H, m; 1.40, 4H, m;
1.00, 3H, m (vi) l-[4-(3-Methoxyprop-l-ynyl)phenyl]-4-n-propyl-3-trifluoromethyl-2,6,7trioxabicyclo(2,2,2]octane was prepared from l-(4-iodophenyl)-4-n-propyl3- trifiuoromethyl-2,6,7-trioxabicyclo[2,2,2]octane and methyl propargyl ether using the methodology described in Example 3.
' 4-n-Butyl-l-(4-(3-methoxyprop-l-ynyl)phenyl]-3-trifluoromethyl-2,6,7-trioxabicyclo[2,2,2]octane was prepared from diethyl n-butyl-malonate in a manner analogous to the synthesis of l-[4-(3-methoxyprop-l-ynyl)phenyl]4- n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo{2,2,2)octane
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Example 5 i~U
V ° 10
4-(2,2-Dimethylpropyl)-l-[4-(3-methoxyprop-l-yl)phenyl)-2>6>7-trioxabicyclo[2,2,2] octane (i) Diethyl 2,2-dimethylpropylmalonate (18.8g.) (Brandstrom, Acta. Chem. Scand., 1958, 13, 615) was added to a stirred suspension of sodium hydride (4.0g., 60% dispersion in oil) in dry tetrahydrofuran (150 ml.), at 0*, under nitrogen. The mixture was refluxed, with stirring, for one hour. The mixture was cooled and benzyl chloromethyl ether (13.3g.) in dry tetrahydrofuran (50 ml.) was added dropwise. The reaction mixture was stirred for 24 hours and poured into cold water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water and dried over anhydrous magnesium sulphate. The solvent was removed jn vacuo.
Diethyl 2-benzyloxymethyl-2-(2,2-dimethyl-propyl) malonate was obtained as an oil (28.8g.) and was used without further purification.
(ii) Diethyl 2-benzyloxymethyl-2-(2,2-dimethylpropyl)malonate (15g.) in dry diethyl ether (50 ml.) was added slowly to a stirred suspension of lithium aluminium hydride (7.0g.) in dry diethyl ether (200 ml.) at 0*, under nitrogen. The mixture was stirred at room temperature for 12 hours. Aqueous sodium hydroxide solution (25 mi., 10% solution) was added carefully. The mixture was filtered and the solid was washed with diethyl ether. The filtrates were dried over anhydrous magnesium sulphate and evaporated in vacuo.The residue was purified by chromatography on silica, eluting with 1:4 ethyl acetate : hexane. 2-Benzyloxymethyi-2-(2,2dimethylpropyl)-propan-l,3-diol was obtained as a colourless oil (5.5g.).
(iii) 2-Benzyloxymethyl-2-(2,2-dimethylpropyl)-propan-l,3-diol (5.5g.) in dry diethyl ether (50ml.) was added to liquid ammonia (200 ml.) at -70*. Sodium (2.5g.) was added to the stirred solution. Stirring was maintained at -70*, for 1 hour. The mixture was allowed to warm up to -30* and solid ammonium chloride (15g.) was added cautiously. The ammonia was removed from the reaction mixture under a current of nitrogen. Methanol (25 ml.) was added to the stirred mixture to destroy residual sodium. Dichloromethane (400 ml.) was added and the mixture was filtered. The ii/n bad original d
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- 30 P16 filtrates were evaporated in vacuo. 2-(2,2-Dimethylpropyl)-2hydroxymethyl-propan-l,3-diol was obtained as a colourless solid (3.5g.).
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDClp integral, number of peaks);
4.20, 3H, broad, exchanged with D2O» 3.80, 6H, s; 1.40, 2H, s; 1.20, 9H, s.
(iv) Trimethyl 4-bromo-orthobenzoate (1.5g.) (McElvain and Venerable, J. 10 Amer.Chem.Soc., 1950,72,1661) was added to 2-(2,2-dimethylpropyl)-2hydroxymethyl-propan-l,3-diol (l.Og.). One drop of concentrated hydrochloric acid was added and the mixture was maintained at 140* for one hour, under a current of nitrogen. The volatile components were removed in vacuo (1.0 mm), at 140 *C.
The residue was purified by chromatography on alumina (Alumina Woelm TSC), eluting with 1:20 dichloromethane:hexane, saturated with ammonia. l-(4-Bromophenyl)-4-(2,2-dimethylpropyl)-2,6,7-trioxabicyclo[2,2,2]octane was obtained as a colourless solid (0.7Qg.).
Gas-liquid chromatography (g.l.c.) :
0V101 at 250* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCly integral, number of peaks):
7.50, 4H, s; 4.20, 6H, s; 1.20, 2H, s; 1.00, 9H, s.
Mass Spectrum (M.S.), Chemical Ionisation:
M + 1 341 343
APO 00 0 6 5 (v) n-Butylithium (5.0 mi.of 1.6 M solution in hexane) was added to a stirred 35 * solution of l-(4-bromophenyl)-4-(2,2-dimethylpropyl)-2,6,7trioxabicyclo(2,2,2]octane (0.5g.) in dry diethyl ether (50 ml) at -70·, under a current of nitrogen. The reaction mixture was allowed to warm up slowly to room temperature and the progress of the reaction was monitored by gas liquid chromatographic analysis. When all the starting
bad original f, <
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- 31 P16 material had disappeared iodine (l.Og.) in dry diethyl ether (50 ml.) was added to the stirred reaction mixture. After 10 minutes on aqueous solution of sodium thiosulphate (3g. in 40 ml. water) was added. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.The residue was purified by chromatography on alumina, eluting with 5% dichloromethane : hexane, saturated with ammonia.
4-(2,2-Dimethylpropyl)-l-(4-iodophenyl)-2,6,7-trioxabicyclo(2,2,2]octane was obtained as a colourless solid.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCly integral, number of peaks):
Mass Spectrum (M.S.), Chemical Ionisation
M + 1 389 vi) Using methodology described in Example 3, 4-(2,2-dimethylpropyl)-l-[4(3-methoxyprop-l-ynyl)phenyl]-2,6,7-trioxabicycIo [2,2,2] octane was prepared from 4-(2,2-Dimethylpropyl)-l-(4-iodophenyl)-2,6,7-trioxabicyclo [2,2,2]octane and methyl propargyl ether.
vii) Using methodology described in Example 1, 4-(2,2-dimethylpropyl)-l-[4(2-trimethylsilylethynyl)phenyl]-2,6,7-trioxabicyclo(2,2,2]octane was prepared from 4-(2,2-dimethyi-propyl)-l-(4-iodophenyl)-2,6,7trioxabicyclo (2.2.2] octane and trimethylsilylacetylene.
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Example 6
N-Methyl-3-[^-(4-n-propyl-2,6,7-trioxabicyclo[2,2,21oct-I-yl)phenyl]prop-2-ynyl carbamate
A solution of 3-[4-(4-n-propyl-2,6,7-trioxabicycIo [2,2,2] octyl)phenyl]-prop-2-ynl-ol (0.5g), methyl isocyanate (0.2g), and triethylamine (O.lg) in dry benzene (50ml) was refluxed for 6 hours. The solution was cooled and evaporated m vacuo.
The residue was purified by chromatography on alumina, eluting with 1:5 dichloromethane: hexane, saturated with ammonia.
N-Methyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl) phenyl] prop-2-ynyI carbamate was obtained as a colourless solid (0.25g m.p.t. 136.2°).
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Example 7
3-[4-(4-n-Propyl-2,6,7-trioxabicyclo [2,2,2} oct-l-yl) phenyl] prop-2-ynyl acetate
Acetyl chloride (0.33ml) was added to a stirred solution of 3-[4-(4-n-propyl-2,6,7 trioxabicyclo[2,2,2]octyl)phenyl]-prop-2-yn-l-ol (l.lg) and triethylamine (0.8ml) in dry diethyl ether, at 0°C, under nitrogen. The mixture was stirred for 12 hours at room temperature and poured into water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
The residue was· purified by chromatography on alumina, eluting with 3:2 dichloromethane:hexane, saturated with ammonia.
3-[4-(4-n-Propyl-2,6,7-trioxabicyclo [2,2,2] oct-l-yl) phenyl] prop-2-ynyl acetate was obtained as colourless crystals (0.90g m.p.t. 98.0°).
N,N-Dimethyi-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yi)phenyl]-prop-2ynamide and N,N-dimethyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-lyl)phenyl]-prop-2-ynthioamide were prepared using similar methodology from 1(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane and dimethylcarbamoyl chloride and dimethylthiocarbamoyl chloride respectively.
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Example 8
4-η-Ρ ropy l-l-[4-(prop-l-ynyl)-phenyll-2,617-trioxabi cyclo [2,2,2] octane n-Butyllithium (0.79ml of 1.6M solution, in hexane) was added to a stirred solution of l-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane (0.25g) in dry tetrahydrofuran, at 0°, under nitrogen. The reaction was stirred at 0° for 10 minutes. Methyl iodide (90 vl) was added and the mixture was stirred at room temperature for 5 hours. The solvent was removed in vacuo.
Water was added and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
*>15 4-n-Propyl-l-[4-(prop-l-ynyl)-phenyl]-2,6,7-trioxabicyclo[2,2,2]octane was obtained as colourless crystals (0.20g., recrystallised from dichloromethane:hexane).
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Example 9
3-Cyano-l-[4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane
i) A mixture of 2-n-propyl-2-hydroxymethyl-propan-l,3-dioI (24.6g), diethyl carbonate (20.1ml.), potassium hydroxide (0.3g) and dry ethanol (2ml) was heated to gentle reflux (oil bath 110—120°) under a stream of nitrogen for 30 minutes. After this time the ethanol formed was removed by distillation at atmospheric pressure (oil bath 130-140°, still head temperature 76°). The pressure was reduced to 20mm.Hg and the oil bath temperature adjusted to 230°. 3-hydroxymethyl-3-n-propyl oxetane distilled as a colourless liquid (16.7 gms, head temperature 120-126°).
Gas-liquid chromatography (g.l.c.): OV-210 at 120° produced one peak. Nuclear magnetic resonance spectrum (N.M.R.) was as follows; (ppm from TMS in CDCl^, integral, multiplicity);
AP 0 0 0 0 6 5
4.35, 4H, s; 3.60, 2H, mj 1.8-0.7, 7H, m.
ii) A solution of dimethyl sulphoxide (12ml) in dry dichloromethane (4.0ml) was added to a solution of oxalyl chloride (7.4ml) in dichloromethane (25ml) stirred at -70° under nitrogen. After the addition was complete the resulting mixture was stirred for a futher 5 minutes at -70° before a solution of 3-hydroxymethyl-3-n-propyloxetane (10.Og) in dichloromethane (25ml) was added, dropwise, over 10 minutes. The resulting mixture was allowed to stir for a further 30 minutes when neat triethylamine (54ml) was added over approximately 30 minutes. The reaction mixture was allowed to warm to room temperature over 3 hours when it was poured into water. The organic phase was separated and the aqueous layer further extracted with fresh dichloromethane. The combined organic extracts were washed with dilute hydrochloric acid, saturated sodium bicarbonate and brine. The resulting organic phase was dried over anhydrous magnesium sulphate and evaporated in vacuo to give 3-formyl3-n-propyloxetane (10.5g) as a yellow oil.
Gas-liquid chromatography (g.l.c.); OV-210 at 120° produced one peak. Infrared spectrum (1R) (liquid film); 1730cm”^
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Nuclear magnetic resonance spectrum (N.M.R]) was as follows: (ppm from TMS in CDCl^, integral, multiplicity, JHz; 9.0, 1H, s; 4.90, 2H, d, 6; 4.60, 2H, d, 6; 2.30-1.0, 7H, m.
w tf 10 ;>
p iii) To a stirred solution of 3-formyl-3-n-propyl-oxetane (3.0g) and 4iodobenzoyl chloride (6.2g) in diethyl ether (75ml), under nitrogen, was added a solution of sodium cyanide (1.6g) in water (2.0ml). The mixture was stirred overnight. The mixture was poured into water (50ml) and the aqueous mixture was extracted diethyl ether. The ethereal solution was dried over anhydrous sodium sulphate and then evaporated in vacuo. The residue was chromatographed on silica pre-treated with triethylamine and eluting with hexane:chloroform 1:3.
The 4-iodobenzoate of 3-(a-cyano-hydroxymethyl)-3-n-propyl-oxetane was obtained as a colourless solid (6.5g m.p.t. 90°)
Nuclear magnetic resonance spectrum (NMR) was as follows: (pp from TMS in CDClj, integral, number of peaks, JHz):
7.90, 2H, d, 7; 7.80, 2H, d, 7; 5.70, 1H, s; 4.65, 4H, m; 1.95, 2H, m;
1.50, 2H, m; 1.00, 3H, t, 6.
Mass Spectrum (M.5.), Chemical Ionisation
386 iv) Using methodology described in stage iii of Example 1, 3-cyano-l-(4iodophenyl)-4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane (colourless, crystals, mpt 129°) was prepared from the 4-iodobenzoate of 3-(a-cyano30 hydroxymethyl)-3-n-propyI-oxetane.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDCl-j, integral, number of peaks, JH^):
35 . 7.75, 2H, d, 7; 7.35, 2H, d, 7; 4.95, lH,d, 2; 4.40, 1H, m; 4.15, 3H, m;
1.60-1.40, 4H, m; 1.00, 3H, t, 6.
Mass Spectrum (MS), Chemical Ionisation , _ BAD ORIGINAL
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Μ + 1 386
ν) Using methodology described in Example 3, 3-cyano-l-[4-(3-methoxypropl-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2] octane was prepared from 3-cyano-l-(4-iodophenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane.
£ 'u
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Example 10 $0 □>
£ l-(4-(3-Methoxyprop-l-ynyl)-phenyl]-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane
i) Diethyl n-propyl malonate (20.Og) was added to a stirred suspension of sodium hydride (4.8g. 50% dispersion in oil) in dry toluene (200 ml.), under nitrogen. The mixture was stirred at 80* for one hour. The mixture was cooled and benzyl chioromethyi thioether (J.L. Wood and V.du Vigneaud, J.Biol.Chem.1939,131,267) (16.Og.) in dry toluene (50ml) was added and the mixture was stirred at 80 * for two hours. The mixture was cooled and poured into water. The aqueous mixture was extracted into diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Diethyl 2benzylthiomethyl-2-n-propyl malonate (30.Og.) was obtained as a yellow oil and was used without further purification.
ii) Diethyl 2-benzylthiomethyl-2-n-propyl malonate (30.Og.) in dry diethyl ether (60ml.) was added to a stirred suspension of lithium aluminium hydride (7.0g.) in dry diethyl ether (400ml.), at 0*, under nitrogen. The mixture was stirred at room temperature for three hours and then refluxed with stirring for a further three hours. The mixture was cooled and 10% aqueous sodium hydroxide solution (25ml.) was added very carefully. The mixture was filtered and the solid was washed with ether. The filtrates were dried over anhydrous magnesium sulphate and evaporated in vacuo. 2-Benzylthiomethyl-2-n-propyl-propan-l,3-diol was obtained as a colourless solid (20g.) and was used without further purification.
iii) 2-Benzylthiomethyi-2-n-propyl-propan-l,3-diol (7.0g.) in dry diethyl ether (150ml.) was added to liquid ammonia (150ml.) at -70*. Sodium (1.8g.) was added to the stirred solution. Stirring was maintained at -70*, for one hour. The mixture was then allowed to warm up to -30* and solid ammonium chloride (lOg.) was added cautiously.
» The ammonia was removed from the reaction mixture under a current of nitrogen. The residue was washed with dry dichloromethane and the filtrates were evaporated jn vacuo. 2,2-Di-hydroxymethyl-pentan-l-thiol (3.2g.) was obtained as a colourless smelly oil and was used without further purification.
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Using a method analogous to that described in stage iv of Example 5 2,2di-hydroxymethyl-pentan-l-thiol and trimethyl 4-bromo-orthobenzoate were reacted together to give l-(4-bromophenyl)-4-n-propyl-2,6-dioxa-7thiabicyclo[2,2,2]octane (colourless solid).
Gas-liquid chromatography (glc): OV 210 at 200* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCl-j, integral, number of peaks):
Infrared spectrum (lR)(nujol mull): 1080(s),1040(s),1020(m).
Mass spectrum (MS), chemical ionisation:
M+l 329,331.
n-Butyliithium (16ml., 1.6M solution in hexane) was added to a stirred solution of l-(4-bromophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2.2.2] octane (1.7g) in dry diethyl ether (150ml) at -70°, under nitrogen. The reaction mixture was allowed to warm up slowly to room temperature and the progress of reaction was monitored by g.l.c. analysis. When all the starting material had disappeared iodine (6.6g) in dry diethyl ether (50ml) was added and this was followed immediately by the addition of an aqueous solution of sodium thiosulphate (lOg in 70ml water). The mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulphate. The solvent was removed in vacuo.
The residue was purified by chromatography on alumina (Alumina Woelm TSC) eluting with 1:10 dichloromethane:hexane, saturated with ammonia.
. l-(4-Iodophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo(2,2,2]octane was obtained as colourless crystals (0.8g mpt 128-132°)
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClp integral, number of peaks, JHz)jAJR/EB/2.9.86
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7.70, 2H, d, 7; 7.40, 2H, d, 7; 4.15, 4H, m;3.10, 2H, m; 1.30, 4H, m; 0.95, 3H, m.
Mass spectrum (MS), chemical ionisation;
M + 1 377 vi) A mixture of l-(4-iodophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo [2,2,2)octane (0.20g), methyl propargyl ether (67 yl) bis(triphenylphosphine)palladium (II) chloride (50mg) and cuprous iodide (25g) in dry triethylamine (10ml) was stirred at room temperature, under nitrogen for 24 hours.
The solvent was removed m vacuo. The residue was extracted with diethyl ether and the ethereal extracts were washed with water. The 15 extracts were dried over anhydrous magnesium sulphate and the solvent was removed in vacuo.
The residue was purified by chromatography on alumina (alumina Woelm TSC), eluting with 1:5 dichloromethane:hexane, saturated with ammonia.
l-[4-(3-Methoxyprop-l-ynyl)phenyl) 4-n-propyl-2,6-di oxa-7-thi abicyclo[2,2,2]octane was obtained as a colourless solid (20mg).
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDCl-j, integral, number of peaks, JHz);7.60, 2H, d, 6; 7.45, 2H, d, 6; 4.30, 2H, s;4.20, 4H, m; 3.50, 3H, s; 3.10, 2H, m; 1.30, 4H, m; 0.95, 3H, m.
Mass spectrum (MS), chemical ionisation
M +1 319
Using the methodology outlined above 4-n-propyl-l-[4-(235 trimethylsilylethynyl)phenyl)-2,6,-dioxa-7-thiabicyclo[2,2,2]octane was prepared from l-(4-iodophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane and trimethylsilylacetylene and using diethylamine instead of triethylamine as solvent.
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4-n-propy l-l-[4-(2-trimethylsilylethynyl)phenyl]-2,6-di oxa-7-thiabicy cl o(2,2,2] octane was obtained as a colourless crystalline solid.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDClj, integral, number of peaks, J(_|z);·
7.50,4H,m; 4.20,4H,m; 3.15,2H,m; 1.35,4H,m; 1.05,3H,m; 0.40,9H,m.
Mass spectrum (MS), chemical ionisation
M + 1 347 l-(4-Ethynylphenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane was prepared from 4-n-propyl-l~(4-(2-trimethylsiIylethynyl)phenyl]-2,6-dioxa-7thiabicyclo[2,2,2]octane using methodology outlined in stage (i) of Example 2.
15 l-(4-Ethynylphenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane was obtained as a colourless solid.
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDClp integral, number of peaks, JHz)s7.50,4H,m; 4.20,4H,m; 3.20,3H,m; 1.30,4H,m; 1.00,3H,m.
Mass spectrum (MS), chemical ionisation 25
M + 1 275
59000OdV »
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Example 11
4-t-Butyl-I-(4-ethynylphenyl)-2,6,7-trioxabicyclo [2,2,2] octane
Vb000063
i) To a solution of £-vinylbenzoic acid (5g, 34 mmol) in chloroform (50mi) at
0°C was added Br^ (35 mmol) in chloroform with stirring. The mixture was allowed to stand overnight and then was evaporated to dryness, leaving crude 4-(1,2-dibromoethyl)benzoic acid, 10.4g, (99%). This was suspended in dry benzene (100ml), thionyl chloride (8.3g) was added and the mixture was heated sufficiently to cause it to reflux for 3 hours. The solution was evaporated to dryness to give the acid chloride as a solid.
ii) To a stirred solution to 3-t-butyl-3-hydroxymethyIoxetane (2.16g, 15 mmol) in dry dichloromethane (30ml) containing pyridine (1.5ml) at 0°C 15 under a nitrogen atmosphere was added a solution of 4-(1,2-dibromoethylbenzoyl chloride (5g, 16 mmol) from above. The mixture was allowed to warm to room temperature and was stirred overnight. The resulting solution was washed with water, dried over sodium sulfate and evaporated to leave the oxetane ester, 6.5g. The product was characterised by NMR 20 (300 MHz, CDCI3): δ 1.05, 9H, s; 3.95-4.1, 2H, m; 4.45, 2H, s; 4.6, 4H, d of d; 5.15 1H, d of d; 7.5, 2H, dj 8.1, 2H, d;
To a stirred solution of the oxetane ester (6.5g, 15mmol) in dry dichloromethane (35 ml) under a nitrogen atmosphere at -70 *C was added boron trifluoride etherate (1 ml). The solution was allowed to warm to room temperature and was stirred overnight. The reaction mixture was quenched with dry triethylamine and evaporated to dryness. The residue was partitioned between water and dichloromethane and the organic layer was separated, dried over K^CO^ and evaporated to leave crude 4-t30 butyI-l-[4-(l,2-dibromoethyl)phenyl]-2,6,7-trioxabicyclo[2,2,2]octane.
This compound was characterized by NMR (300 MHz, CDCl^); δ 0.9, 9H, s; 3.9-4.05, 2H, m; 4.15, 6H, s; 5.1, 1H, d of d; 7.35, 2H, d; 7.6, 2H, d;
Small pieces of sodium were added to liquid ammonia until a blue colour 35 * persisted. Ferric nitrate (100 mg) was added and the solution was stirred.
When the solution turned colourless, sodium (6g) was added in small pieces. After about 30 to 35 minutes following the addition the blue colour disappeared and a solution of the above dibromoethylphenyl bicyclooctane in tetrahydrofuran was added to the solution. The ammonia
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Utilizing the procedure described above (i) 4-cyclohexyl-l-(4ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane and (ii) 4-n-propyl-l-(4ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane were prepared from the respective oxetanes.
Thus 3-cyclohexyl-3-hydroxymethyloxetane and 3-n-propyl-3hydroxymethyloxetane were reacted with 4-(1,2-dibromoethyl)benzoyl chloride by the method of example 11. The resulting products were characterized by NMR (300 MHz, CDClj).
The oxetane esters so produced were reacted with boron trifluoride etherate as described above to yield (i) 4-cyclohexyl-l-(4-(l,2dibromoethyl)phenyl)-2,6,7-trioxabicyclo[2,2,2]octane and (ii) 4-n-propyl1-(4-(1,2-dibromoethyl)phenyl)-2,6,7-trioxabicyclo[2,2,2]octane. The products were characterized by NMR (300 MHz, CDCl-j); (i) δ 0.9 - 1.3 and 1.5 -1.9, 11H, m; 3.9 - 4.1, 2H, m; 4.1 6H,s; 5.1 1H, d of d; 7.35 2H, d; 7.6, 2H, d; (ii) δ 0.9, 3H, t, 1.15 - 1.35, 4H, m, 3.9 - 4.1,
2H, m; 4.1, 6H, s; 5.1, 1H, d of d; 7.35, 2H,d, aromatic; 7.6, 2H, d;
S 9 0 0 0 0 dV
The dibromoethylphenyl bicyclics were dehydrobrominated as described above to yield the desired l-(4-ethynylphenyl)-2,6,7trioxabicyclo[2,2,2]octanes.
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AJR/EB/2.9.86
- 43P16 eaooeoqi'
Example 12 l-]4-(2-t-Butyldimethylsilylethynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octane n-Butyllithium (0.79 ml of 1.6 M solution, in hexane) was added to a stirred solution of l-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicycl o[2,2,2] octane (0.25g.) in dry tetrahydrofuran (15 mi) at 0*, under nitrogen. The reaction mixture was stirred at 0 * for 10 minutes. _t-Butyldimethylsilyl chloride (0.23g.) was added and the mixture was stirred at room temperature for 6 hours. The reaction mixture was evaporated m vacuo. Water was added and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated jn vacuo. The residue was purified by chromatography on alumina (Alumina Woelm TSC), eluting with 2:3 dichloromethane : hexane saturated with ammonia. l-[4-(2-tButyldimethylsilylethynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo(2,2,2]octane was obtained as pale yellow crystals (0.32g.)
Using the above methodology l-[4-(2-methylthioethynyl)phenyl]-4-n-propyl-2,6,720 trioxabicyclo[2,2,2]octane was prepared from l-(4-ethynylphenyl)-4-n-propyl2,6,7-trioxabicyclo[2,2,2Joctane and s-methyl methanethiosulphonate (Eluka
A.G.).
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AJR/EB/9.9.86
- 44 P16
Example 13
N-Methyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]-prop-2-yn-amide n-Butyllithium (1.6 ml) of 1.6 M solution in hexane) was added to a stirred solution of l-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane (0.5g) in dry tetrahydrofuran (15 ml), under nitrogen, at 0*. The mixture was stirred at 0 * for 10 minutes and methyl isocyanate (0.17 ml.) was added. After 1 hour the mixture was evaporated in vacuo. Water was added and the aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
The residue was purified by chromatography on alumina (Alumina Woelm TSC), eluting with 1: 4 dichloromethane : hexane saturated with ammonia.
N-Methyl-3-[4-(4-n-propyl-2,6,7-trioxabicycio[2,2,2]oct-l-yl)phenyI]-prop-2-ynamide was obtained as colourless crystals (0.095g.).
N-Methyi-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]-prop-2-yn20 thioamide was prepared from l-(4-ethynylphenyl)-4-n-propyl-2,6,7trioxabicyclo[2,2,2]octane and methyl isothiocyanate in a manner analogous to the synthesis of N-Methyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-lyl)phenyl]-prop-2-ynamide.
AP000065
AJR/EB/2.9.86
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-45Ρ16
Example 14 j-(4-(4-n-Propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl)prop-2-ynyl methanesulphonate
Methanesulphonyl chloride (0.19 ml.) was added to a stirred solution of 3-[4-(4-n propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]-prop-2-yn-l-ol (0.6g.) in dry pyridine (0.34 ml.) and dry dichloromethane (20 ml.) at 0*, under nitrogen. The mixture was stirred for 1 hour at 0*. The mixture was poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated jn vacuo.
The residue was purified by chromatography on alumina (Alumina Woelm TSC) eluting with 1 : 1 dichloromethane : hexane saturated with ammonia.
3-[4-(4-n-Propyl-2,6,7-trioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynyl methanesulphonate was obtained as colourless crystals (0.18g.).
BAD ORIGINAL
AJR/EB/9.9.86
- 45A P16
Example 15 l-[4-(3-Ethylthioprop-l-ynyl)phenyll-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
To a solution of ethanethioi (O.O53ml.) in dry tetrahydrofuran (20ml.) at 0*,under nitrogen, was added n-butyllithium (0.45ml. of 1.6M solution in hexane). The solution was stirred for 10 minutes and a solution of 3-[4-(4-n-propyl-2,6,7trioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynyl methanesulphonate (0.25g.) in dry tetrahydrofuran (5ml.) was added dropwise. After 2 hours the mixture was evaporated jn vacuo.Water was added and the aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous megnesium sulphate and evaporated in vacuo.
The residue was purified by chromatography on alumina (Alumina Woelm TSC), eluting with 1:1 dichloromethane : hexane saturated with ammonia.
l-[4-(3-Ethylthioprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane was obtained as an off-white waxy solid (0.21g.).
AP000065
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Example 16 l-[4-(3-EthylsuIphinylprop-l-ynyl)phenyll-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane
A solution of l-[4-(3-ethylthioprop-l-yny!)phenyl]-4-n-propyl-2,6,7trioxabicyclo(2,2,2]octane (0.20g.) and 3-chloroperoxybenzoic acid (0.16g.) in
Vb ο o (feo e a dichloromethane (25ml.) was stirred at room temperature for 30 minutes. The solution was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and finally brine. The dichloromethane solution was dried over anhydrous magnesium sulphate and then evaporated in vacuo.
The residue was purified by chromatography on alumina (Alumina Woelm T5C) eluting with 1:1 dichloromethane : hexane saturated with ammonia.
-(4-(3 -E thy lsulphinylprop-l-ynyl)phenyl]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane was obtained as an off-white solid (0.08g.).
l-[4-(2-Methylsulphinylethynyl)phenyI]-4-n-propyl-2,6,7-trioxabicyclo[2,2,2]octane was prepared by the above method from l-[4-(2-methylthioethynyl)phenyl]-4-npropyl-2,6,7-trioxabicyclo(2,2,2]octane.
The various spectra and nuclear magnetic resonance spectra of various compounds of the invention are set in the Tables below.
AJR/EB/9.9.86
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- 53 PI6 ii) BIOLOGICAL ACTIVITY
A. Lethal Activity Against Houseflies
The activity of compounds of the invention against unanaesthetised female
Musca domestica (WRL strain), was demonstrated by the topical application to the test insect of a solution of the compound under test in butanone.
The activity of the test compound was also assessed when applied topically in conjun ction with the synergist piperonyl butoxide (6vg piperonyl butoxide (PB) per insect). Mortality was assessed after 24 and 48 hours.
The following compounds were active at less than 30 vg/fly:
1,2,3,13,14,15,16,17,19,20,21,22,23,26,27
The following compounds were active at less than 1 vg/fly:
8, 11
B. Lethal Activity Against Blattella germanica
The activity of compounds of the invention against anaesthetised male Blattella germanica (WRL strain) was demonstrated by the topical application to the test insect of a solution of the compound under test in butanone.
The activity of the test compound was assessed when applied topically in conjunction with the synergist piperonyl butoxide(10vg piperonyl butoxide per insect). Mortality was assessed after 24 and 48 hours.
The following compounds were active at less than 50 vg/insect:
1,7,8,11,13,17,20 35
The following compounds were active at less than 5vg/insect:
2,3,15,16,19,21
AP 0 0 0 0 6 5
4-5 -e4OOR|GmMt $
AJR/EB/2.9.86
- 54 Ρ16
Vb Ο Ο 041 ο .>
Ο
C. Lethal Activity Against Sitophilus qranarius
The activity of the compounds of the invention against S.granarius adults was demonstrated by addition of the compound in acetone solution to grain, to which the insects were later infested. Mortality was assessed after 6 days.
The following compounds gave activity at less than 200 ppm solution of acetone:
8,11,15,20,21,22,23,26
The following compounds gave activity at less than 50 ppm solution of acetone:
2.14.16.19.27
D. Lethal activity against Culex quinquefasciatus
The activity of the compounds of the invention against female Culex adults was demonstrated by direct spraying of 0.5 ml of compound in OPD/Methylene chloride. Mortality was assessed after 24 hours.
The following compounds were active at less than 1.0%
1.14.19.21.23.26.27
E. Mammalian Toxicity
Compound 2 has an LD^g value of approximately 20mg/kg when given orally to mice (Charles River CD1).
Compound 4 has an LD^g value of greater than 200mg/kg when given orally to mice (Charles River CD1).
AJR/EB/2.9.86
- 55 P16
Formulations
1. Emulsifiable Concentrate
Compound of formula (I)
Ethylan KEO
Xylene
Butylated Hydroxyanisole
10.00
20.00
67.50
2.50
100.00
AP000065
2. Wettable Powder
Compound of formula (1)
Attapulgite
Sodium isopropylbenzene sulphonate Sodium salt of condensed naphthalene sulphonic acid
Butylated hydroxytoluene
25.0
69.50 0.50
2.50 2.50
100.00
3. Dust
Compound of formula (I) Butylated Hydroxyanisole Talc
0.50
0.10
99.40
100.00
AJR/EB/2.9.86
- 56 P16
4. Bait
Compound of formula (I) Icing Sugar
Butyiated hydroxy toluene
40.25
59.65
0.10
100.00
5. Lacquer
Compound of formula (I) Resin
Butyiated Hydroxy anisole High aromatic white spirit
2.5
5.0
0.5
92.0
100.00
6. Aerosol
Compound of formula (I) 2q Butyiated Hydroxy anisole
1,1,1-T richloroethane
Odourless Kerosene Arcton 11/12. 50:50 mix
7. Spray
Compound of formula (I) ^Butyiated Hydroxy anisole
Xylene jn Odourless Kerosene
0.30
0.10
4.00
15.60
80.00
100.00
0.1
0.1
10.0
89.8
100.00
Λ f, »
AJR/EB/2.9.86
- 57 P16
8. Potentiated Spray
Compound of formula (I) 0.1
Piperonyl Butoxide 0.5
Butylated Hydroxyanisole 0.1
Xylene 10.1
Odourless Kerosene 89.2
100.0
Claims (2)
1. A compound of the formula (I):
R
Αϊ
4>
(I) wherein R is C2_10 alkyl, alkenyl or alkynyl, each optionally substituted by, or methyl substituted by,
5 cyano, halo, C3_4 cycloalkyl, Cj_4 alkoxy, or a group
S(O)mR4 where R4 is C^_4 alkyl and m is 0, 1 or 2, or R i C3-10 cycloalkyl, C4_1Q cycloalkenyl or phenyl, each optionally substituted by C^_4 alkoxy, C^_^ alkyl, C2_4 alkynyl, halo, cyano or a group S(0)mR4 as defined
10 hereinbefore;
1 3
R and R , which are the same or different, each is hydrogen, halo, C^_3 alkyl, C2_3 alkenyl or alkynyl, the alkyl, alkenyl or alkynyl each being optionally substituted by halo, cyano or C^_4 alkoxy; alkyl
15 carbalkoxy containing up to 6 carbon atoms, a group
S(0) R as defined hereinbefore or alkynyl substituted by m .
tri-C^_4 alkylsilyl, or R is COO-C^_4~alkyl, cyano, gemdimethyl, gem-dicyano, gem-dihalo, gem-diethynyl, spirocyclopropyl, spiro-oxirane or oxetane, substituted
20 spiro-oxirane or oxetane, oxo or methylene optionally substituted by cyano, halo or
-CF3 or r! and R and the carbon atoms to which they are attached form a carbocyclic ring optionally substituted by C^_3 alkyl or alkoxy or C2_3 alkenyl;
25 *R2 is a phenyl group substituted at the 4-position by a group -(CfC)nR^ and optionally substituted at other
SET B
P16 positions of the phenyl ring, wherein n is 1 or 2, is 4 x hydrogen, bromine, chlorine, iodine, a group S(0) R
4x 4 m 4 wherein R is trifluoromethyl or a group R and m and R are as hereinbefore defined, an optionally substituted
5 aliphatic or cycloaliphatic group containing up to 9 carbon atoms, a group -CX.R® where X is oxygen or sulphur and r6 is a hydrocarbyl or hydrocarbyloxy group optionally substituted by fluoro or an amino group optionally substituted by one or two C^_4 alkyl groups or
10 r5 is cyano, or a silyl group substituted by three 4 alkyl groups or two C^_4 alkyl groups and a phenyl group;
Y and γΐ are the same or different and are each selected from oxygen and S(0)m where m is 0, 1 or 2;
Z is CH2CHg, CH2CH20, sulphur, CH20, CH2S, CHR1XNR7
15 wherein R^ is hydrogen, cyano, halo, a group CO2R^ or alkyl, C2-3 al*<enyl or alkynyl each optionally substituted by halo, cyano, C, . alkoxy, alkyl carbalkoxy 1-4 4 containing up to 6 carbon atoms or a group S(0) R wherein
4 7 m m and R are as hereinbefore defined and R is hydrogen, p p
20 benzyl, C, , alkyl, C(0)R wherein R is C,_. alkyl, 14 9 9 14 alkoxy or a group NHR wherein R is C^_4 alkyl, C^_g aralkyl or phenyl optionally substituted by halo or Z is -CO.CH2~ or -CH (Or1%CH2- wherein R^ is hydrogen, C^_4 alkyl, C^_4 acyl or C-^_g carbamoyl, the first-mentioned
25 atom in the definition of Z being adjacent to the 4-position of the bicyclic ring system;
with the proviso that when R5 is hydrogen or a silyl group substituted by three alkyl groups and Y and Y1 are oxygen 1 3 and Z is CH20, then R and R must be hydrogen.
30 2. A compound according to claim 1 in which R is n-propyl, n-butyl, i^-butyl, t-butyl, or cyclohexyl.
AP0 00 0 6 5.
SET B ί » Zf .
/ n
9 ‘ /
P16
-v
Ο
Ο ο
3. A compound according to either claim 1 or 2 in which is hydrogen, methyl, trifluoromethyl or cyano.
4. A compound according to any one of the preceding claims wherein is hydrogen, trimethylsilyl,
5 substituted methyl or substituted ethyl, the substituents being at least one hydroxy or methoxy group.
5. A compound according to any one of the preceding claims wherein n is 1 and the phenyl group R is further substituted in positions 3 and/or 5 by halo;
10 cyano; azido; nitro; c^_3 alkyl or alkoxy, each optionally substituted by halo; or C2_^ alkenyl or alkynyl, each optionally substituted by halo.
6. A compound preceding claims in which trifluoromethyl.
according to any one of the R5 is hydrogen, methyl or
7. A compound according to any one of the preceding claims wherein Y is 0, is 0 and Z is Cf^O or ch2s.
8. A compound of the formula IA:
(IA) wherein Ra is C2-7 alkenyl or alkynyl, each optionally substituted by cyano, halogen or C|_4 alkoxy, or Ra is cycloalkyl, cycloalkenyl or phenyl, each optionally substituted by C^_^, alkoxy, C^_3 alkyl, C2_4 alkynyl, halogen or cyano;
SET B
BAD ORIGINAL CM
- X P16
Rla is hydrogen, C3_3 alkyl, C2_3 alkenyl or alkynyl each optionally substituted by cyano, C^_4 alkoxy, C^_4 alkylthio, alkyl carbalkoxy containing up to 6 carbon atoms or halo, or R^a is cyano, gem-dimethyl or R^a and Ra and the carbon atoms to which they are attached form a C5_7 carbocyclic ring optionally substituted by Cj_3 alkyl, or C2_3 alkoxy or alkenyl;
R^a is a phenyl group substituted at the 4-position by a group -C=C-R^a and optionally substituted at other 5a positions of the phenyl ring, wherein R is an optionally substituted C^_g aliphatic group,a group -CO.R^a where R^a is a hydrocarbyl or hydrocarbyloxy group or an amino group optionally substituted by one or two C, . alkyl 5a groups or R is cyano, or a silyl group substituted by three C^_4 alkyl groups or two C^_4 alkyl groups and a phenyl group; and R^a is hydrogen, C^_3 alkyl, C2_3 alkenyl or alkynyl each optionally substituted by cyano, C^_4 alkylthio, C^_4 alkoxy or halo;
Ya and Y^a are the same or different and are each selected from oxygen or S(O)m where m is 0, 1 or 2;
Za is CH2CH2, CH2CH20, sulphur, CH20, CH2S or CH2NR7a wherein R7a is hydrogen, benzyl, C, , alkyl, C(0)R®a 8 a wherein R is C^_4 alkyl or alkoxy, or Z is -CO.CH2~ or -CH(OR1Oa)CH2~ wherein R10a is hydrogen, C3_4 alkyl, C^_4 acyl or C3_3 carbamoyl.
9. l-[3-nitro-4-(2-trimethylsilylethynyl)phenyl]-4-n-propy1-2,6,7-trioxabicyclo[2,2,2]octane; l-(4-ethynylphenyl)-4-n-propy1-2,6,7-trioxabicyclo[2,2,2]octane;
,4-n-butyl-l-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane;
4-_i-butyl-l- (4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane;
AP000065
SET B
P16 •Xl-(4-ethynylphenyl)-4-n-pentyl-2,6,7-trioxabicyclo[2,2,2]octane;
4-ri-pentyl-l- [4- (2-tr imethyls ilylethynyl) phenyl]-2,6,7trioxabicyclo[2,2,2]octane;
5 l-[3-chloro-4-(2-trimethylsilylethynyl)phenyl]-2,6,7trioxabicyclo[2,2,2]octane;
4-propyl-1-[4-(2-tr imethylsilylethynyl) phenyl] - 2,6,7trioxabicyclo[2,2,2]octane;
1-[4-(3-methoxyprop-l-ynyl) phenyl]-4-propyl-2,6,710 trioxabicyclo[2,2,2] octane;
4-ri-butyl-l- [4-(2-trimethylsilylethynyl) phenyl )-2,6,7trioxabicyclo-[2,2,2]octane;
4-_i-buty 1-1- [4 - (2-tr imethy Is ilylethynyl) phenyl )-2,6,7trioxabicyclo-[2,2,2]octane;
15 1-[4-(3-ethoxyprop-l-ynyl) phenyl]-4-n-propyl-2,6,7trioxabicyclo[2,2,2]octane;
4-methoxy-l-[4-(4-n-propyl-2,6,7-tr ioxabicyclo[2,2,2]oct-l-yl)phenyl]but-l-yne;
4-i-butyl-1-[4-(3-methoxyprop-l-ynyl-phenyl)-2,6,720 trioxabicyclo[2,2,2]octane;
N-[3-[4-(4-n-propyl-2,6,7-tr ioxabicyclo[2,2,2]oct-l-yl) phenyl]prop-2-ynyl]acetamide;
4-(2,2-dimethylpropyl)-1-(4-ethynylphenyl)-2,6,7trioxabicyclo[2,2,2]octane;
25 methyl 3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct -1-yl)-phenyl]prop-2-ynoate l-(3-chloro-4-ethynylphenyl)-4-n-propyl-2,6,7trioxabicyclo[2,2,2]octane;
1- (4-ethynyl-3-nitrophenyl)-4-n-propyl-2,6,730 trioxabicyclo[2,2,2]octane;
4-(t-butyl-1-(4-ethynylphenyl )-2,6,7-trioxabicyclo[2,2,2]octane;
SET B
BAD ORIGINAL
- X63
P16
4-cyclohexyl-l-(4-ethynylpheny1)-2,6,7-trioxabicyclo[2,2, 2]octane;
4-t-butyl-l - [4-(3-methoxyprop-l-ynyl)phenyl]-2,6,7trioxabicyclo-[2,2,2]octane;
5 l-[3-chloro-4-(3-methoxyprop-l-ynyl)phenyl]-4-npropy 1- 2 , 6 , 7- tr ioxabicyclo[2,2,2]octane;
4-cyclohexyl-1-[4-(3-methoxyprop-l-ynyl)phenyl]2.6.7- tr ioxabicyclo(2,2,2]octane;
4-n-butyl-l-[4-(3-methoxyprop-l-ynyl)phenyl]10 2,6,7-trioxabicyclo[2,2,2]octane;
1-[4-(3-methoxyprop-l-ynyl)phenyl]-4-n-penty1-2,6,7tr ioxabicyclo[2,2,2]octane;
1-(4-(3-methoxyprop-l-ynyl)phenyl]-4-n-propy1-3tr i fluoromethyl-2,6,7-tr ioxabicyclo[2,2,2]octane;
15 3-cyano-l-[4-(3-methoxyprop-l-ynyl)phenyl] - 4-n-propy1
-2,6,7-trioxabicyclo[2,2,2]octane;
4-(2,2-dimethylpropyl )-1-[4-(3-methoxyprop-l-yl)phenyl]2.6.7- trioxabicyclo [2,2,2]octane;
4-(2,2-dimethylpropy1) —1 — [4—(2 — trimethylsilylethynyl) 20 phenyl]2,6,7-trioxabicyclo[2,2,2]octane;
N-methyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]— oct-l-y1)phenyl]prop-2-ynyl carbamate?
3- (4-(4-n-propy1-2,6,7-tr ioxabicyclo[2,2,2]octyl)pheny1]prop-2-yn-l-ol;
25 3-(4-(4-n-propy1-2,6,7-tr ioxabicyclo[2,2,2]oct-l-yl)phenyl]prop-2-ynyl acetate;
4- n-propyl-1-[4-(prop-l-ynyl)-phenyl]-2,6,7trioxabicyclo[2,2,2]octane;
1-(4-(3-methoxyprop-l-ynyl)-phenyl]-4-n-propy1-2,6-d ioxa-7
30 -thiabicyclo[2,2,2]octane;
•1- [4- (2-t-butyld ime thyl si lyle thynyl) phenyl] -4-n-propyl2.6.7- trioxabicyclo[2,2,2]octane;
APO00065
SET B sad
Ρ16
Vb Ο 0 o o ·)
3- [4-(4-n-propyl-2,6,7-trioxabicyclo]2,2,2]oct-l-yl)pheny 11 prop-2-yny 1 methanesulphonate;
N-methyl-3-14-(4-n-propyl-2,6,7-trioxabicyclo]2,2,2) oct-l-yl)phenyl]prop-2-ynamide;
5 N-methyl-3-[4-(4-n-propyl-2,6,7-trioxabicyclo[2,2,2]oct-1-y1) phenyl]prop-2-ynth ioamide;
4- n-butyl-l-[4-(3-methoxyprop-l-ynyl)phenyl]-3tr ifluotomethy1-2,6,7-trioxabicyclo[2,2,2]octane; 4-t-butyl-l-14-(2-tr imethylsilylethynyl)phenyl]10 2,6,7-trioxabicyclo]2,2,2]octane;
4-cyclohexyl-l-[4-(2-trimethylsilylethynyl)phenyl]2,6,7-trioxabicyclo[2,2,2]octane;
1-14-(pent-l-ynyl)phenyl]-4-n-propyl-2,6,7trioxabicyclo[2,2,2]octane;
15 4-ethyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2,2,2]octane;
1-(4-ethynylphenyl)-4-phenyl-2,6,7-trioxabicyclo/T,2,2~7octane ;
4-Phenyl-l-/4-(2-trimethylsilylethynylphenyl)_^2,6,720 trioxabicyclo/2,2, j?7octane ;
4-n-Propyl-l-/4-(2-trimethylsilylethynylphenyl2/-2,6dioxa-7-thiabicyclo/2,2,27°ctane;
1-(4-ethynylphenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo/2,2,27octane ·
25 10· A process for the preparation of a compound as defined in any one of claims 1 to 9 which comprises reacting a compound of the formula CH=C-R^ where is as defined in any one of claims 1 to 9 with a compound of the formula :
where R, R , R , Y, Y^ and Z are as defined in any one of claims 1 to 9 and R2x is a group as defined for R2 in any one of claims 1 to 9 except that the substituent at the 4-position on the phenyl ring is iodo. BAD ORIGINAL
P16
- X11. A process according to claim 10 for the production of a compound in which both Y and Y^ are 0 and Z is wherein the compound of formula IB is prepared by cyclisation of a compound of formula II:
R^x and R^ are (II)
AP 0 0 0 0 6 5 where R,
R1, as defined in claim 10.
12. A process for the preparation of a compound as defined in any one of claims 1 to 9 wherein R^ is H and n is 1 which comprises dehydrobromination of a compound of
10 formula:
,2y (IC) where R, claims 1 to 9 and R 1 is a group as defined for R in any one of claims 1 to 9 except the substituent at the 4-position on the phenyl ring is 1,2-dibromoethyl.
15 13. A process according to any one of claims 10 to 12 substantially as hereinbefore described with reference to any of Examples 1 to 14.
SET B
- zP16
14. A compound of formula I as defined in any one of claims 1 to 9 whenever obtained by a process
. An insecticidal or acaricidal composition compound of formula (I) as defined in any or to 9 in admixture with a carrier or diluent, . A synergised pesticidal composition compound of formula (I), as defined in any one of claims 1 to 9, a synergist for the formula I compound and a carrier or diluent.
17. A mixture of a compound of formula (I) as defined in any one of claims 1 to 9 and another pesticidal compound .
18. A composition or mixture according to any 15 one of claims 15 to 17 substantially as hereinbefore described with reference to any one of Formulations 1 to 7.
19. A method for the control of pests comprising application to the pest or to an environment
20 susceptible to pest infestation of a compound according to any one of claims 1 to 9 or 14 or a composition or mixture according to any one of claims 15 to 18.
-, 2 P16 substituted by Cj_-j alkyl or alkoxy or C2_j alkenyl; i
R/is a phenyl group substituted at the 4-position by a group -(C^C)nRJ and optionally substituted at other positions of the phenyl ring, wherein n is 1 or 2,
R^ is hydrogen, bromine, chlorine, iodine, a group S(O)mR^x wherein R^x is trifluoromethyl or a group R4 and m and R^ are as hereinbefore defined, an optionally substituted aliphatic or cycloaliphatic group containing up to 9 carbon atoms, a group -CX.R^ where X is oxygen or sulphur and R^ is a Cj hydrocarbyl or hydrocarbyloxy group optionally substituted by fluoro or an amino group optionally substituted by one or two alkyl groups or R^ is cyano, or a silyl group substituted by three alkyl groups or two Cj alkyl groups and a phenyl group;
Y and γΐ are the same or different and are each selected from oxygen and S(0) where m is 0, 1 or 2; Z is CP^CP^, CP^CP^O, sulphur, CP^O, CP^S, CPIR^NR^ wherein r1x is hydrogen, cyano, halo, a group CC^R^ or alkyl, C2 3 alkenyl or alkynyl each optionally substituted by halo, cyano, Cj alkoxy, alkyl carbalkoxy containing up to 6 carbon atoms or a group S(O) R4 wherein m and
4 7 m 8
R are as hereinbefore defined and R is hydrogen, benzyl, C, < alkyl, C(O) R
G 99 1-4 wherein R is C^_^ alkyl, alkoxy or a group NPIR wherein R is alkyl, C? θ aralkyl or phenyl optionally substituted by halo or Z is -CO.CP^- or CH(OR10)CPl2-wherein R10 is hydrogen, C^ alkyl, C14 acyl or C^ carbamoyl, except that when R^ is hydrogen or a silyl group substituted by three alkyl I 13 groups^ and Y and Y are oxygen and Z is CP^O? then R and R must be hydrogen.
In the definition of Z, the first mentioned atom is adjacent to the 4-position of the bicyclic ring system.
Suitably R is propyl, butyl, pentyl, C2_c, alkenyl or alkynyl, C^ 7 cycloalkyl or phenyl each optionally substituted by fluoro, chloro or bromo. Most suitably R is n-propyl,n-butyl, i-butyl, sec-butyl, t-butyl, cyclopentyl or cyclohexyl and preferably R is n-propyl, n-butyl, i-butyl, t-butyl or cyclohexyl.
Suitably R^ is hydrogen, cyano, methyl or ethyl each optionally substituted by cyano, methoxy, methylthio, chloro, bromo or fluoro. Most suitably R1 is hydrogen, methyl, cyano, trifluoromethyl or ethyl. Preferably R* is hydrogen, methyl, cyano or trifluoromethyl.
or R is bromine, chlorine or iodine s 9 0 0 0 0 dV
AJR/EB/2.9.86
6 _ °RIGINAL
P16
J3 positions of the phenyl ring, wherein n is 1 or 2, R^ is 4 x hydrogen, bromine, chlorine, iodine, a group S(0) R
4 x 4 m 4 wherein R is trifluoromethyl or a group R and m and R are as hereinbefore defined, an optionally substituted
5 aliphatic or cycloaliphatic group containing up to 9 carbon atoms, a group -CX.R^ where X is oxygen or sulDhur and is a 0·^_θ hydrocarbyl or hydrocarbyloxy group optionally substituted by fluoro or an amino group optionally substituted by one or two C. . alkyl groups or
5 1-4
10 R is cyano, or a silyl group substituted by three 0^.-4 alkyl groups or two C, . alkyl groups and a phenyl group;
1 1 4
Y and Y are the same or different and are each selected from oxygen and S(0) where m is 0, 1 or 2;
Z is CH2CH2, CH2CH20, sulphur, CH20, CH2S, CHR1XNR7 lx 4
15 wherein R is hydrogen, cyano, halo, a group CO2R or alkyl, C2_2 alkenyl or alkynyl each optionally substituted by halo, cyano, C._. alkoxy, alkyl carbalkoxy • · 14 4 containing up to o carbon atoms or a group S(0) R wherein
4 7 m m and R are as hereinbefore defined and R is hydrogen,
20 benzyl, C, . alkyl, C(0)R^ wherein Ηθ is C, . alkyl, 4 9 9 4 alkoxy or a group NHR wherein R is C^ alkyl, C-j _θ aralkyl or phenyl optionally substituted by halo or Z is - CO.CH2~ or -CH (OR·*·^) CH2~ wherein is hydrogen, C^_^ alkyl, acyl or C^_^ carbamoyl, the first-mentioned
25 atom in the definition of Z being adjacent to the 4-position of the bieye 1ic ring system;
with the proviso that when R^ is hydrogen or a silyl group 1 substituted by three alkyl groups^and Y and Y are oxygen and Z is CH20, then and R^ must be hydrogen.
30 2. A compound according to claim 1 in which R is n-propyl, n-butyl, ^“butyl, t-butyl, or cyclohexyl.
SET B or is bromine, chlorine or iodine
Bad ORIGi^t
P16 . A compound of formula I as defined in any one of claims 1 to 9 whenever obtained bv a process /J ' according to any one of claims 10 to )S5.
. An insecticidal or acaricidal composition comprising a compound of formula (I) as defined in any one or 13 of claims 1 to 9λιπ admixture with a carrier or diluent.
/£·
X.
A synergised pesticidal composition comprising a compound of formula (1), as defined in any or 13 one of claims 1 to a bynergist for the formula I comoound and a carrier or diluent.
AP000065 yf. A mixture of a compound ~ c formula (I) as ot defined in any one of claims 1 to 9^and another pesticidal comoound .
com one of claims 15 described with re 1 to 7.
ion ar^mixture according to any tantially as hereinbefore one of Formulations /? S ys. A method for the control of pests comprising application to the pest or to an environment susceptible to pest infestation of a compound according to any one of claims 1 to 9 or or a composition or mixture /-x z£according to any one of claims to P8.
Ρ16
11. A process according to claim 10 for the production of a compound in which both Y and YA are 0 and Z is CH20 wherein the compound of formula 13 is prepared by cyclisation of a compound of formula II:
(II.
1 2x 3 where R, R , R and R are as defined in claim 10,
12. A process for the preparation of a compound as def i ned in any one of claims 1 to 9 wherein R^ is H and n is 1 which comprises dehydrobromination of a compound of
10 formula:
(1C) where R, RJ
R^, γ, γΐ and Z are as defined in any one of
2v 2 claims 1 to 9 and R - is a group as defined for R in any one of claims 1 to 9 except the substituent at the rim the phenyl ring is 1,2-dibromoethy1 iZ
A process
Sordino to anv one of claims 10 to 12 substantially a s ^h,e\e i nbe f o r e described with reference’ to any of Examples, 1 to 14.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/779,167 US4772624A (en) | 1985-01-23 | 1985-09-23 | 1,4-bis-substituted-2,6,7-trioxabicyclo(2.2.2)-octanes having ethynyl substituted phenyl group |
Publications (2)
Publication Number | Publication Date |
---|---|
AP8600045A0 AP8600045A0 (en) | 1986-08-01 |
AP65A true AP65A (en) | 1989-12-12 |
Family
ID=25115548
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
APAP/P/1986/000045A AP65A (en) | 1985-09-23 | 1986-09-22 | Pestcidal compounds. |
Country Status (4)
Country | Link |
---|---|
US (1) | US4772624A (en) |
AP (1) | AP65A (en) |
DD (2) | DD260497A5 (en) |
ZA (1) | ZA867208B (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5098929A (en) * | 1985-07-30 | 1992-03-24 | The Wellcome Foundation Limited | Pesticidal compounds |
GB8606130D0 (en) * | 1986-03-12 | 1986-04-16 | Wellcome Found | Pesticidal compounds |
US5116862A (en) * | 1985-09-24 | 1992-05-26 | The Wellcome Foundation Limited | Pesticidal compounds |
US5466710A (en) * | 1988-03-21 | 1995-11-14 | Roussel Uclaf | Heterobicycloalkanes as pesticidal compounds |
CA2008348A1 (en) * | 1989-01-24 | 1990-07-24 | John P. Larkin | Pesticidal compounds |
TWI550071B (en) | 2011-03-25 | 2016-09-21 | 捷恩智股份有限公司 | Orthoester compound,liquid crystal composition and liquid crystal display device |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3686224A (en) * | 1970-02-24 | 1972-08-22 | Gulf Research Development Co | 2,6,7-trioxabicyclo(2.2.2)octane compounds |
EP0052229A1 (en) * | 1980-11-14 | 1982-05-26 | Societe Des Produits Nestle S.A. | Canning process and apparatus |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3113068A (en) * | 1960-09-19 | 1963-12-03 | Diamond Alkali Co | Aromatic ethynyl pesticides |
JPS59985A (en) * | 1982-06-25 | 1984-01-06 | Nec Corp | Drive circuit for semiconductor laser |
FI863091A (en) * | 1985-07-30 | 1987-01-31 | Wellcome Found | OIL PESTICID. |
-
1985
- 1985-09-23 US US06/779,167 patent/US4772624A/en not_active Expired - Lifetime
-
1986
- 1986-09-22 DD DD86294595A patent/DD260497A5/en not_active IP Right Cessation
- 1986-09-22 ZA ZA867208A patent/ZA867208B/en unknown
- 1986-09-22 AP APAP/P/1986/000045A patent/AP65A/en active
- 1986-09-22 DD DD86321060A patent/DD275604A5/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3686224A (en) * | 1970-02-24 | 1972-08-22 | Gulf Research Development Co | 2,6,7-trioxabicyclo(2.2.2)octane compounds |
EP0052229A1 (en) * | 1980-11-14 | 1982-05-26 | Societe Des Produits Nestle S.A. | Canning process and apparatus |
Also Published As
Publication number | Publication date |
---|---|
DD260497A5 (en) | 1988-09-28 |
US4772624A (en) | 1988-09-20 |
AP8600045A0 (en) | 1986-08-01 |
ZA867208B (en) | 1988-05-25 |
DD275604A5 (en) | 1990-01-31 |
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