AP66A - Pestcidal compounds. - Google Patents
Pestcidal compounds. Download PDFInfo
- Publication number
- AP66A AP66A APAP/P/1986/000046A AP8600046A AP66A AP 66 A AP66 A AP 66A AP 8600046 A AP8600046 A AP 8600046A AP 66 A AP66 A AP 66A
- Authority
- AP
- ARIPO
- Prior art keywords
- alkyl
- octane
- compound
- formula
- dioxa
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 125
- 238000000034 method Methods 0.000 claims abstract description 22
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 113
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 238000009472 formulation Methods 0.000 claims description 19
- -1 CH20 Chemical compound 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 241000607479 Yersinia pestis Species 0.000 claims description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 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 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 239000005864 Sulphur Substances 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 230000000361 pesticidal effect Effects 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 150000002367 halogens Chemical group 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 230000000895 acaricidal effect Effects 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000000749 insecticidal effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
- STYFZWLGHRPJGN-UHFFFAOYSA-N 1-(4-chlorophenyl)-4-propyl-2,6-dioxabicyclo[2.2.2]octan-8-ol Chemical compound C1C(O)C(CCC)(CO2)COC12C1=CC=C(Cl)C=C1 STYFZWLGHRPJGN-UHFFFAOYSA-N 0.000 claims 1
- NQNNNGWTZIELFS-UHFFFAOYSA-N 1-(4-chlorophenyl)-4-propyl-2,6-dioxabicyclo[2.2.2]octan-8-one Chemical compound C1C(=O)C(CCC)(CO2)COC12C1=CC=C(Cl)C=C1 NQNNNGWTZIELFS-UHFFFAOYSA-N 0.000 claims 1
- PPLFMIYKAAOLGZ-UHFFFAOYSA-N 1-tert-butyl-4-cyclohexyl-5,8-dioxa-3-thiabicyclo[2.2.2]octane Chemical compound O1CC(C(C)(C)C)(CS2)COC12C1CCCCC1 PPLFMIYKAAOLGZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- DHBUOJMHAPQWHL-UHFFFAOYSA-N 4-(4-bromophenyl)-1-butan-2-yl-5,8-dioxa-3-thiabicyclo[2.2.2]octane Chemical compound O1CC(C(C)CC)(CS2)COC12C1=CC=C(Br)C=C1 DHBUOJMHAPQWHL-UHFFFAOYSA-N 0.000 claims 1
- XBYYJHCCTQDJSG-UHFFFAOYSA-N 4-(4-bromophenyl)-1-propyl-5,8-dioxa-3-thiabicyclo[2.2.2]octane Chemical compound O1CC(CCC)(CS2)COC12C1=CC=C(Br)C=C1 XBYYJHCCTQDJSG-UHFFFAOYSA-N 0.000 claims 1
- KXSLCMKULJZFCY-UHFFFAOYSA-N 4-(4-bromophenyl)-1-propyl-8-oxa-3,5-dithiabicyclo[2.2.2]octane Chemical compound S1CC(CCC)(CS2)COC12C1=CC=C(Br)C=C1 KXSLCMKULJZFCY-UHFFFAOYSA-N 0.000 claims 1
- LFGMNSJCRMRTRX-UHFFFAOYSA-N 4-(4-bromophenyl)-1-tert-butyl-5,8-dioxa-3-thiabicyclo[2.2.2]octane Chemical compound O1CC(C(C)(C)C)(CS2)COC12C1=CC=C(Br)C=C1 LFGMNSJCRMRTRX-UHFFFAOYSA-N 0.000 claims 1
- SHGMFUZIPNWULV-UHFFFAOYSA-N 4-(4-bromophenyl)-2-methyl-1-propyl-5,8-dioxa-3-thiabicyclo[2.2.2]octane Chemical compound O1CC(CCC)(C(S2)C)COC12C1=CC=C(Br)C=C1 SHGMFUZIPNWULV-UHFFFAOYSA-N 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 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 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims 1
- 239000000575 pesticide Substances 0.000 abstract description 2
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 239000002917 insecticide Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 72
- 239000000243 solution Substances 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 238000001819 mass spectrum Methods 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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 46
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- 239000003921 oil Substances 0.000 description 36
- 235000019198 oils Nutrition 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 238000000451 chemical ionisation Methods 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 23
- 239000000284 extract Substances 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 238000002329 infrared spectrum Methods 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000001030 gas--liquid chromatography Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 239000007921 spray Substances 0.000 description 11
- 241000238631 Hexapoda Species 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- CFOZPJJVBOHJPL-UHFFFAOYSA-N 1-bromo-4-(trimethoxymethyl)benzene Chemical compound COC(OC)(OC)C1=CC=C(Br)C=C1 CFOZPJJVBOHJPL-UHFFFAOYSA-N 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 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 7
- 239000006185 dispersion Substances 0.000 description 7
- 239000004495 emulsifiable concentrate Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 6
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003350 kerosene Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- 241000238421 Arthropoda Species 0.000 description 4
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 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 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 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
- 229960005235 piperonyl butoxide Drugs 0.000 description 4
- 239000004540 pour-on Substances 0.000 description 4
- 239000002453 shampoo Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- ZYGASOKADXEEFS-UHFFFAOYSA-N 2-(2-methylpropyl)-2-(sulfanylmethyl)propane-1,3-diol Chemical compound CC(C)CC(CO)(CO)CS ZYGASOKADXEEFS-UHFFFAOYSA-N 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 3
- 241000256054 Culex <genus> Species 0.000 description 3
- 206010061217 Infestation Diseases 0.000 description 3
- 241000257159 Musca domestica Species 0.000 description 3
- 239000004133 Sodium thiosulphate Substances 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- OFRFGNSZCYDFOH-UHFFFAOYSA-N diethyl 2-(2-methylpropyl)propanedioate Chemical compound CCOC(=O)C(CC(C)C)C(=O)OCC OFRFGNSZCYDFOH-UHFFFAOYSA-N 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 239000004922 lacquer Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- OKKVLEFAHISYEI-UHFFFAOYSA-N (3-cyclohexyloxetan-3-yl)methanol Chemical compound C1CCCCC1C1(CO)COC1 OKKVLEFAHISYEI-UHFFFAOYSA-N 0.000 description 2
- AHRXGYCFTIZWPO-UHFFFAOYSA-N 1-(3-cyclohexyloxetan-3-yl)-n-methylmethanamine Chemical compound C1CCCCC1C1(CNC)COC1 AHRXGYCFTIZWPO-UHFFFAOYSA-N 0.000 description 2
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- 239000003380 propellant Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003573 thiols 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
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (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 0, s and n substituted at the 1-position by a carbocyclic group other than an alkynylphenyl group, and substituted at the 4 position and optionally substituted at the 3 and/or 5 position, are valuable pesticides, particularly insecticides and acaracides. Various cyclisation processes are disclosed to form the various bicyclo ring systems.
Description
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 heterabicycloalkanes.
The use of certain 2,6,7-trioxabicyclo {2,2,2)octanes as pesticides is disclosed in European Patent Application No. 152229; it has now been discovered that derivatives of these compounds in which at least one of the ring oxygens has been substituted have interesting pesticidal activity.
Accordingly the present invention provides a compound of the formula (I):
wherein R is alkyl, alkenyl or alkynyl, each optionally substituted by, or methyl substituted by, cyano, cycloalkyl, , halo, alkoxy or a group
S(0)m R^ where R^1 is alkyl and m is 0, 1 or 2; or R is cycloalkyl, cycloalkenyl or phenyl, each optionally substituted by alkoxy, alkyl, alkynyl, halo,cyano or a group SCOJmR^ as defined hereinbefore;
is hydrogen, halo, a group CO^R^ wherein R^ is alkyl, or is alkyl, C2 j alkenyl or alkynyl each optionally substituted by halo, cyano, alkoxy, alkyl carbalkoxy containing up to 6 carbon atoms or a group S(O)mRu as defined hereinbefore or or R1 is cyano, gem dimethyl, spiro-cyclopropyl, gem dicyano, gem diethynyl, oxo or methylene optionally substituted by cyano, or trifluoromethyl, or R^ is C2 alkynyl substituted by tri alkylsilyl or and R and the carbon atoms to which they are attached form a carbocyclic ring optionally substituted by halo, alkyl or alkoxy, or C2_^ alkenyl;
,2 .
R is phenyl, cycloalkyl or cycloalkenyl each optionally substituted ;
R^ is hydrogen, Cj alkyl, C? alkenyl or alkynyl each optionally substituted by cyano, Cj alkylthio, alkoxy or halo or R^is cyano or halo; and Y and γΐ are the same or different and are e^^i^lected from oxygen or S(O)m where m is 0, 1 or 2 and Z is CH2 c CH2O, CH2S, CHRlxNR5 < 2_SEH9do Be ώ·*·..
8SB^ —
AJR/EB/2.9.86 &AD Original
-2P7/12 lx 6 wherein R is hydrogen, cyano, halo, a group CC^R or alkyl, C2^ alkenyl or alkynyl each optionally substituted by halo, cyano, alkoxy, alkyl carbalkoxy containing up to 6 carbon atoms or a group S(O)mR^ wherein rn and
R^ are as hereinbefore defined and R^ is hydrogen, benzyl, C. , alkyl or C(O)
6 7 1 7
R wherein R is C, . alkyl, alkoxy or a group NHR wherein R is C, , alkyl,
J. * Μ I g*
C7 θ aralkyl or phenyl optionally substituted by halo or Z is -CH(OR ) -CH~ wherein R is hydrogen, alkyl, Cj acyl, C2 carbamoyl or a group SC^R wherein R^ is alkyl or -CH(OR )-CH2- is -CO.CH2-; provided : (i) that when Z is CHR^XNR^’ R^ and R^ are hydrogen,(ii) that when Y and Y' are both oxygen, Z is not CH^O, and (iii) that R is not phenyl substituted by an optionally substituted C2 alkynyl group.
In the definition of Z the first atom is adjacent to the 4-position of the bicyclic ring system.
Suitably R is propyl, butyl, pentyl, C2 alkenyl or alkynyl, ? cycloalkyl or phenyl. Most suitably R is n-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, cyclopentyl, cyclohexyl or phenyl and preferably R is n-propyl, n-butyl, i-butyl, t-butyl or cyclohexyl.
Suitably is hydrogen, cyano, ethynyl, methyl or ethyl optionally substituted by cyano, methoxy, methylthio or fluoro. Most suitably R^ is hydrogen, methyl, cyano, trifluoromethyl or ethyl. Preferably R^ is hydrogen, methyl or trifluoromethyl.
When R is a substituted phenyl, cycloalkyl or cycloalkenyl group, suitable substituents include halo, cyano, azido, nitro, alkyl or alkoxy optionally substituted by halo or alkenyl optionally substituted by halo. Suitably when R2 is phenyl it is substituted by up to three substituents which are preferably at the 3,4 and/or 5-positions.
Suitably R is cyclohexyl, cycloheptyl or phenyl optionally substituted at the 3,4- and/or 5 position by chloro, bromo, iodo, cyano, azido or nitro and/or phenyl optionally substituted at the 2-and/or 6-position by fluoro. Most suitably R is cyclohexyl or phenyl optionally substituted at the 4-position by chloro, bromo iodo or cyano.
Suitably is hydrogen or alkyl, preferably R^ is hydrogen.
AP 0 0 0 0 6 6
AJR/EB/2.9.86
BAD ORIGINAL A
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Suitably Z is -CH^S-, -CH^O- or -CHjCHp Preferably Z is -CR^S- or -CR^CR.
Suitably Y and Y1 are both oxygen or both sulphur.
One group of compounds of formula (1) is that of formula (IA):
Cl
,1a (IA)
5-7
Q wherein R is C2 η alkyl, alkenyl or alkynyl, each optionally substituted by cyano halogen or alkoxy, or R is Cj.jq cycloalkyl, C^_^g cycloalkenyl or phenyl, each optionally substituted by alkoxy, C·^ alkyl, alkynyl, halogen or cyano; R is hydrogen, C^ alkyl, alkenyl or alkynyl each optionally substituted by cyano,alkoxy, Cj alkylthio, alkyl carbalkoxy T 3 13 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 C 2d carbocyclic ring optionally substituted by C, , alkyl or alkoxy, R is phenyl, jg cycloalkyl or cycloalkenyl each optionally substituted and R?a is hydrogen, Cj, j alkyl, C2 3 alkenyl or alkynyl each optionally substituted by cyano, Cj alkylthio, Δ alkoxy or halo; Ya and Y^a are the same or different and are each selected from oxygen and S(O) where m is 0, 1 or 2 ; Z is CRL m Δ ά 2
CR^jCR^CR^O, sulphur, CR^O, CR^S, CRL NR a wherein R a is hydrogen, Cj alkyl, benzyl or C(O) R^a wherein R a is C^ alkyl or alkoxy,or Za is CH(OR^a) CH2- wherein R^a is hydrogen, C^ alkyl or C^_^ acyl or -CRI(OR^a)CRI2- is -CO.CRI2-; except that when Ya and Y^a are both oxygen, then Za is not ch2o.
Suitably R is propyl, butyl, ? cycloalkyl or phenyl. Most suitably R is npropyl, t-butyl, cyclopentyl or cyclohexyl and preferably Ra is n-propyl, t-butyl or cyclohexyl.
Suitably R is hydrogen cyano, methyl or ethyl optionally substituted by cyano,
4θ methoxy, methylthio or fluoro. Most suitably R la is hydrogen, methyl,
8AB ORIGINAL
AJR/EB/2.9.86 pvu
-41 3 tri fluoromethyl or ethyl. Preferably R is hydrogen or methyl.
When R is a substituted phenyl, jg cycloalkyl or cycloalkenyl group, suitable substituents include halo, cyano, azido, nitro, Cj_-j alkyl optionally substituted by halo or C2 alkenyl or alkynyl each optionally substituted by halo.
2a
Suitably R is cyclohexyl, cycloheptyl or phenyl optionally substituted at the 32a or 4-position by halo, cyano, C2 3 alkynyl, azido or nitro. Most suitably R is cyclohexy, or phenyl optionally substituted at the 4-position by chlorine, bromine, C2 -j alkynyl or cyano.
When Za contains a hetero atom this is adjacent to the carbon atom of the
3 bicyclooctane ring having the substituent R
Suitably Za is -Ch^S- -Ch^CH^O- or -CH2CH2-.
13
Suitably Y and Y are both oxygen
A further group of compounds of the formula (IA) is as defined above except that
6s in addition to the values listed R can be j carbamoyl.
Preferred compounds include l-(4-bromophenyl)-4-j-butyI-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-(4-bromophenyl)-4-j-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-(4-bromophenyl)-4-s-butyl-2,6,-dioxa-7-thiabicyclo[2,2,2]octane l-(4-chlorophenyl)-4-s-butyl-2,6-dioxa-7-thiabicyclo[2,2,2Joctane 4-£-butyl-l-cyclohexyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-(4-bromophenyI)-3-methyl-4-n-propyl-2,6-dioxa-7-thiabicycIo-(2,2,2]octane 1-cyclohex yI-5-n-propyl-2,7,8-tr ioxabic yclo[2,2,2]nonane I-(4-chlorophenyl)-4-n-propyl-2,6-dioxabicyclo(2,2,2]octane l-(4-bromophenyl)-4-n-propyl-2,6-dioxa-7-thiabicydo[2,2,2]octane 4-t-butyI-l-(4-chlorophenyl)-2,6-dioxabicyclo(2,2,2]octane l-(4-chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane l-(4-chlorophenyl)-8-methoxy-4-n-propyl-2,6-dioxabicyclo [2,2,2]octane l-(4-chlorophenyl)-8-oxo-4-n-propyl-2,6-dioxabicyclo [2,2,2]octane l-(4-bromophenyl)-4-t-butyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane 4-t-butyl-l-(4-chlorophenyl)-2,6-dioxa-7-thiabicyclo(2,2,2]octane
9 0 0 0 0 dV bad origiNAL
AJR/EB/2.9.86
-5Ρ7/12 . Vb ο 0 ΰ β,β β tn ο l-(4-iodophenyl)-Zi-n-propyl-2,6-dioxa-7-thtabicycio[2,2,2]octane 4-t-buty 1-1 -cyclohexyl-2,6-dioxa-7-thiabieyelo[ 2,2,2] octane 4-L·butyl-l-cycloheptyί-2,6-dioxa-7-thiabιcyclo[2,2,2]octane l-(4-chloropheny!)-4-i_-butyl-2-oxa-6,7-dithiabicyclo[2,2,2]octane 5 l-cyclohexyl-4-n-propyl-2,6,7-trithiabicyclo[2,2,2]octane
1-cyclohexyl-8-methyl-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-(4-bromophenyl)-4-i-butyl-8-methyl-2,6-dioxa-7-thiabicyclo[2,2,2)octane l-(4-bromophenyl)-8-methyl-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2)octane l-(4-bromophenyl)-4-n-butyl-2,6-dioxa-7-thiabicyclo(2,2,2)octane l-(4-bromophenyl)-4-n-propyl-2-oxa-6,7-dithiabicycIo[2,2,2]octane
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 (1) may be any method known in the art for preparing analogous compounds, for example when the compound of the formula (1) contains three hetero atoms by the condensation of a compound of the formula (II) with an 2 9 orthocarboxylate of the formula R C(OR
(II)
9 wherein R to R are as hereinbefore defined, R is alkyl, phenyl or C-j θ aralkyl, Y2 and, Y^ are the same or different and each is oxygen or sulphur and
Z1 is a group CH„CH7OH,SH,CH?OH, CH SH or CHRlxNHR5 except that Y2 and Y are not both oxygen when Z is CH^OH.
This reaction is normally carried out at an elevated temperature, for example between 50 and 200 *C, conveniently between 120 and 170 *C in the presence of a base, for example an amine such as triethylamine or of a mineral acid, for example hydrochloric acid or a sulphonic acid derivative such as toluene sulphonic acid or an acid resin. The reaction may conveniently be carried out in the absence of a solvent but a suitable solvent may be added if desired.
AJR/EB/2.9.86
BAD ORIGINAL J
-6P7/12
The preparation of the compounds of the formula (II) will take place by methods well known to the skilled in the art for preparing compounds of analogous structure. Examples of such methods are shown in the Schemes.
The compounds of the formula (I) wherein Z is CH^CH^ and Y and are each oxygen may be prepared by the deprotection and cyclisation of a compound of the formula (III):
AP 0 0 0 0 6 6 wherein R and R , are as hereinbefore defined, Q is H, the groups R10 are hydroxy protecting groups, and R11 is a C. .
χ * alkyl group. Conveniently the groups R are linked to form, for example, an isopropylidene group but any group that protects the hydroxy groups in the preparation of the compound of the formula (III) and is readily cleaved to permit cyclisation to the compound of the formula (I) is suitable. This cyclisation is conveniently carried out in the presence of a dilute acid that will cleave the protecting group R^, for example a dilute mineral acid such as hydrochloric acid. The reaction is suitably carried out at ambient temperature. The preparation of compounds of the formula (III) is illustrated in the Scheme.
θ
The compounds of formula I wherein Z is CH(OR )CH- and Y and Y are each oxygen may be prepared by a similar deprotection and cyclisation of a compound of formula Til where Q is OH to give initially a compound of formula I having an 8-hydroxy group which may subsequently be 8 8 converted to a group OR e.g. by reaction with R -halide in the presence of base. Compounds TII where Q is OH may be prepared analogously to compounds III where Q is H.
AJR/EB/2.9.86
BAD ORIGINAL
6Α
1x5 1
The compounds of the formula (I) wherein Z is CHR NR and Y and Y are each oxygen are preferably prepared by the cyclisation of a compound of the formula (IV) (Scheme 3)
AJR/EB/2.9.86
SAS ORIGINAL
-7P7/12 ? 1 v 5 wherein R, R , R and R are as hereinbefore defined in the presence of an acid catalyst, such as a Lewis Acid. 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.
The compounds of the formula (IV) may be prepared by the reaction of compounds of the formula (V) and (VI) :
NHR
C L
II (VI)
AP 0 0 0 0 6 6
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 cardried out at between -50 and 100 *C, preferably at 0*C.
The compounds of the formula (V) may in turn be prepared from compounds of the formula (VII) by reaction with an amine (R^NH2) with sodium cyanoborohydride in a polar solvent, such as an alcohol, for example methanol.
(VII)
AJR/EB/7.9.R6 sad ORIGINAL
-8P7/12 •J τ»
Ο
The compound of the formula (VII) is prepared by oxidation of the corresponding hydroxy compound, for example by use of oxalyl chloride, dimethyIsulphoxide and triethylamine. The hydroxy compound may in turn he prepared from compounds of the formula (II) wherein R and R are hydrogen , Y and Y are oxygen and 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.
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 arthorpods which comprises administering to the arthorpod or its environment an arthropodicidally 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 the compounds of the formula (I) for use in human and veterinary medicine for the control of arthropod pests.
The compounds of Formula (1) 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, wettable powder, granule, aerosol, emulsifiable concentrate, oil suspensions, oil solutions, pressure-pack, impreg nated 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 material 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.
AJR/EB/2.9.86
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-9P7/12
The compounds of Formula (1) may be formulated either as formulations ready for use on the animals, plants or surface or as formulations requiring dilution prior to application, hut 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, solid or gaseous or comprise mixtures of such substances, and the compound of Formula (1) 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 (1) in intimate admixture with a powdered solid inert carrier for example suitable clays, kaolin, talc, mica, chalk, gypsum, vegetable carriers, starch and diatomaceous earths.
Sprays of a compound of Formula (1) 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 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.
3Q 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 95% by weight of the active ingredient, and are diluted, for example with water, before use.
AP000066
AJR/EB/2.9.86
SAD ORIGINAL
-10P7/12
9 00 0 ORA
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 agueous suspensions comprising a compound of Formula (1) 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
Ίθ 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.
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 Formula (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 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 mammalian host may also be protected against infestation of acarine ectoparasites by means of carrying a suitably-moulded, shaped plastics article 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.
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
BAD OWGINAi
AJR/EB/2.9.86
-11P7/12 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 5 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 10 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 in 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 15 agricultural use contain between 0.0001% and 50% of a compound of formula (I) and conveniently betwee 0.1 and 15% by weight of a compound of the formula (1).
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.
Ephestia, 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.
Linognathus and Haematopinus spp.), Hemiptera (e.q. Aphis, Bemisia, Aleurodes, AJR/LB/z.y.86 “
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99OOUOdV
P7/12
Nilopavata, Nephrotetix or Cimex spp.), Orthoptera (e.g. Schistoeerca 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 Tetranychus, Psoroptes, Notoedres, Psorerqates, Chorioptes and Demodex spp.
Compounds 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 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 25 compounds of the invention include, for example, antioxidants (such as tocopherols, butylhydroxyanisole and butylhydroxytoluene) and scavengers (such as epichlorhydrin).
The following Examples illustrate, in a non-limiting manner, preferred aspects of the invention. All temperatures are in degrees Celsius. When used herein the term ether refers to diethyl ether.
Example 1 l-(4-chlorophenyl)-4-ethyl-2,6-dioxabicyclo[2,2,2t]octane.
l-(4-chlorophenyl)-4-n-propyl-2,6-dioxabicyclo(2t2t2)octane
AJR/EB/2.9.86
-13P7/12 (i) Methanesulphonyl chloride (15 ml.) was added dropwise to a stirred solution of 2,2-dimethyl-5-ethyl-5-hydroxymethyl-l,3-dioxane (33. Og) in dry pyridine (100ml.) at 0*. The mixture was stirred for two hours at room temperature and then poured into water. The aqueous mixture was extracted with ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. 2,2Dimethyl-5-ethyl-5-hydroxymethyl-l,3-dioxane methane sulphonate was obtained as a colourless oil (39g.) which solidified on standing. The compound was used without further purification.
Gas-liquid chromatography (g.l.c.): OV210 at 150* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from
TMS in CDCl-j, integral, number of peaks):
4.40, 2H, s; 3.70, 4H, s; 3.10, 3H, s; 1.50, 8H, m; 0.90, 3H, m.
(ii) A mixture of 2,2-dimethyl-5-ethyl-5-hydroxymethyl-l,3-dioxane methylsulphonate (6.0g.) and sodium iodide (9.0g.) in ethyl methyl ketone 20 was refluxed, with stirring, for forty-eight hours. The solvent was removed in vacuo and the resulting oil was poured into water. The aqueous mixture was extracted with ether. The ethereal extracts were washed with 5% aqueous sodium thiosulphate solution and then water. The ethereal extracts were dried over anhydrous magnesium sulphate and then evaporated m vacuo. The residue was purified by column chromatography on silica, eluting with 1:10 ether: hexane. 2,2-Dimethyl-5-ethyl-5iodomethyl-l,3-dioxane was obtained as a colourless oil (5.0g.)
Gas-liquid chromatography (g.l.c.): OV210 at 150* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from
TMS in CDClp integral, number of peaks):
3.75,4H,s; 3.45,2H,s; 1.20, 8H,m;0.90, 3H, m, (iii) and (iv)a) 35 n-Butyl-lithium (5.3 ml., 1.6M hexane solution) was added to a stirred solution of 4-chloro-acetophenone Ν,Ν-dimethyIhydrazone (1.5g., b.pt. 8082* 0.05 m.m.) in dry tetrahydrofuran (50 ml.) at -70 ·, under nitrogen. The mixture was stirred at -70 * for thirty minutes. A solution of 2,2AP000066
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dimethyl-5-ethyl-5-iodomethyl-l,3-dioxane (2.4g.) in dry tetrahydrofuran (20 ml.) was added to the stirred mixture at -70*. The mixture was allowed to warm up slowly to room temperature. The mixture was stirred at room temperature for twenty-one hours. Water was added and the mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
The residue (2.9g.) and 2N hydrochloric acid (40 ml.) were stirred at room temperature for twenty-four hours. The aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by chromatography on silica, eluting with 1:20 ether: hexane. 1(4-ChlorophenyI)-4-ethyl-2,6-dioxabicyclo {2,2,2} octane was obtained as colourless crystals (0.6g.) (m.pt. 78 ·).
Gas-liquid chromatography (g.l.c.): OV210 at 210* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (p.p.m.
from TMS in CDClj, integral, number of peaks, JH^):
7.40, 2H, d, 8; 7.30, 2H, d, 8; 4.00, 4H, s; 2.20, 2H, m; 1.90, 2H, m; 1.20, 2H, m; 0.90, 3H. m.
Infrared spectrum (1R) (nujol mull): v 1130(S), 1100(m), 1090(m), 1070(m), 1020(s) cm.’l Mass spectrum (MS), chemical ionisation: M+l, 253.
b) l-(4-chlorophenyl)-4-n-propyl-2,6-dioxabicyclo[2,2,2}octane (m.pt.
94*) was prepared in an analogous manner by substituting 2,ΣΙ la dimethyl-5-n-propyl-5-hydroxymethyl-l,3-dioxane ’ for 2,2dimethyl-5-ethyl-5-hydroxymethyl-l,3-dioxane.
Gas-liquid chromatography (g.l.c.): OV210 at 185* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClj, integral, number of peaks):
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7.10, 4H, m; 5.80, 4H, s; 1.90, 2H, m; 1.70, 2H, m; 1.00, 4H, m; 0.80, 3H, m. Infrared spectrum (1R) (nujol mull): 1130 (s), 1080 (m), 1020 (s). Mass spectrum (MS), chemical ionisation: M+l. 267.
Example 2 l-(4-Bromophenyl)-4-ethyl-2,6-dioxa-7-thiabicyclo(2,2>2) octane.
l-(4-Bromophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane (i) Sodium hydride (340 mg., 50% dispersion in paraffin oil) was added carefully to a stirred solution of thiolacetic acid (500 mg.) in dry dimethylformamide (100 ml.) at 20*. After 30 minutes 2,2-dimethyl-5ethyl-5-iodomethyl-l,3-dioxane (2.0g.) was added. The mixture was refluxed with stirring for 2 hours. The mixture was cooled and poured into water. The aqueous mixture was extracted with ether. The ethereal extracts were washed with water and dried over anhydrous magnesium sulphate. The solution was evaporated in vacuo. The residue was purified by column chromatography on silica, eluting with 1:4 ether:hexane. 5AcetylthiomethyI-5-ethyl-2,2-dimethyl-l,3-dioxane was obtained as a pale yellow oil (1.5g.)
Gas-liquid chromatography (g.l.c.): OV210 at 150* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (p.p.m from TMS in CDCl^, integral, number of peaks JHz):
3.70, 4H, s; 3.20, 2H, s; 2.45, 3H, s; 1.50, 8H m; 0.90, 3H, m (ii) and (iii) 5-Acetylthiomethyl-5-ethyl-2,2-dimethyl-l,3-dioxane (2.0g.) was stirred at 20*, in 10% aqueous sodium hydroxide solution (2.0 ml.) in methanol (20 ml.), for 24 hours under nitrogen. The mixture was neutralised with concentrated hydrochloric acid (0.5ml.). Dowex 50 x 8200 ion exchange resin (H+ form) (l.Og.) was added and the mixture was refluxed with stirring, under nitrogen, for 4 hours. The mixture was filtered and the filtrate was evaporated jn vacuo. Toluene was added to the residue and the mixture was evaporated in vacuo. 2,2-Di(hydroxymethyl)-butanethiol was obtained as a colourless oil and was used without further purification (l.Og.)
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-16Ρ7/12 &800009Α (iv'a) 2,2-Di-(hydroxymethyl)-butanethiol (0.5g.), trimethyl 4-bromo-orthobenzoate 2 (l.Og.) and triethylamine (0.1 ml.) were heated at 130*, under a current of nitrogen, for 45 minutes. The volatile components were removed in vacuo (2.00 mm.), at 140*. The residue was purified by chromatography on alumina (alumina Woelm TSC) eluting with 1:6 dichloromethane: hexane, saturated with ammonia. l-(4-Bromophenyl)-4-ethyl-2,6-dioxa-7thiabicyclo[2,2,2]octane was obtained as colourless crystals (80 mg.).
Gas-liquid chromatography (g.l.c.): OV210 at 200* 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, 4H,m; 3.15, 2H, s; 1.40, 2H, m; 1.00, 3H, m.
Infrared spectrum (1R) (nujol mull): 1090(s), 1035(m), 1022(w)
Mass spectrum (MS), chemical ionisation: M+l 315, 317 (iv)b) Using a method analogous to that described in (iv)(a) above 2,2-di20 (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.
Gas-liquid chromatography (glc): OV 210 at 200* produced one peak.
25 1
Nuclear magnetic resonance spectrum (NMR) was as follows: XH (ppm from TMS in CDClp integral, number of peaks):
7.50, 4H, s; 4.20, 4H, m; 3.20, 2H, m; 1.40, 4H, m; 1.00, 3H, m.
Infrared spectrum (1R) (nujol mull): 1080 (s), 1040 (s), 1020 (m).
Mass spectrum (MS), chemical ionisation:
M+l 329, 331
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Example 3
-Cyclohexyl -5-n-propyl-2,7,8-triox abicyclo(3>Z,21nonane.
(i) Sodium hydride (7.5g., 80% dispersion in oil) was added to a stirred solution of diethyl n-propylmalonate (52g.) in dry benzene (200ml.) at room temperature. The mixture was then refluxed, with stirring for 1 hour. The mixture was cooled and ethyl bromoacetate (42g.) was added dropwise. The reaction mixture was refluxed with stirring for 3 hours. The reaction
IQ mixture was cooled and poured into water and the aqueous mixture was extracted into ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and the solvent was removed jn vacuo.
Distillation gave diethyl 2-ethoxycarbonyl-2-n-propylsuccinate (58g.) a colourless oil (b.pt. 130-6* 2.6 mm.)
Gas-liquid chromatography (g.l.c.): OV210 at 150* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (p.p.m.
from TMS in CDClj, integral, number of peaks, JHz): 4.25, 6H, m; 3.00,
2H, s; 2.00, 2 H, m; 1.50 - 0.80, 14H, m.
(ii) Diethyl 2-ethoxycarbonyl-2-n-propyl-succinate (55.8g) in dry ether (50 ml.) was added slowly to a stirred suspension of lithium aluminium hydride (14.7g.) in dry ether (150ml.) at 0*, under a current of nitrogen. The mixture was stirred at room temperature for three hours and then refluxed, with stirring for four hours. A solution of potassium hydroxide (30.0g.), potassium dihydrogen phosphate (22.Og.) and potassium monohydrogen phosphate (22.Og.) in water (200 ml.) was added to the cooled reaction mixture. The pH was adjusted to 5.0 with glacial acetic acid. The solid was removed by filtration and washed with water (40 ml.) The combined filtrates and washings were evaporated in vacuo. The residue was washed with acetone (3x100ml). The acetone washings were evaporated in vacuo. The residue was washed with chloroform (3x100ml.) and the washings were evaporated in vacuo, Toluene was added and the residue was evaporated in vacuo. 3,3-Di-(hydroxymethyl)-hexan-l-ol was obtained as a colourless oil and was used without further purification.
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Vb ο ο ο ο e δ (iii) From 3,3-Di-(hydroxymethyl)-hexan-l-ol (750mg.) and trimethyl orthocyclohexyl-carboxylate (1.0g\ using the method described in example 2, l-Cyclohexyl-5-n-propy 1-2,7,8 - tri oxabicyclot 3,2,2] nonane (50mg.), a colourless oil, was obtained.
Gas-liquid chromatography (g.l.c): OV210 at 190* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from
TMS in CDClp integral, number of peaks): 3.80, 6H, m; 2.00-0.80, 20H, m.
Infrared spectrum (1R) (liquid film): 1114(s), 1070(s),1040(s), 1010(m) cm
Mass spectrum (MS), chemical ionisation: M+l, 255
Example A
4-t-But yl-l-(4-chloropheny 1)-2,6-dioxabicyclo(2,2,2]octane
A mixture of cyclohexanone (150ml.), 5-t-butyl-2,2-dimethy!-5-hydroxymethyl1,3-dioxane methanesulphonate (17.5g.) (see synthesis of 2,2-dimethyl-5-ethyl-520 hydroxymethyl-1,3-dioxane methanesulphonate and ref.A) and sodium iodide (12g.) was refluxed, with stirring, for 24 hours. The solvent was removed in vacuo and the resulting oil was poured into water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with 5% aqueous sodium thiosulphate solution and then water. The ethereal extracts were dried over anhydrous magnesium sulphate and then evaporated in vacuo.
The residue was purified by column chromatography on silica, eluting with hexane. 3-t-Butyl-3-iodomethyI-(l,5-dioxaspiro[5,5]undecane) was obtained as a colourless oil (14g.) Gas-liquid chromatography (g.l.c.): OV210 at 185* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClp integral, number of peaks, JH^):
3.80, 2H, d, 10; 3.50, 2H, d, 10; 3.40, 2H, S; 1.50, 10H, m; 0.90, 9H, S.
35
A mixture of 3-t-butyl-3-iodomethyl-(l,5-dioxaspiro(5,5]undecane) (3.5g.), ptoluenesulphonic acid (0.5g.) and acetone (200 ml.) was refluxed for 36 hours. The mixture was cooled and sodium hydrogen carbonate (2.0g.) was added. The solvent was removed in vacuo and the resulting oil was poured into water. The BAD ORIGINAL
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-19P7/12 aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and then evaporated in vacuo. 5-t-E3utyl-2,2-dimethyl-5-iodomethyl-l,3-dioxane was obtained as a colourless oil (2.3g.) and was used without further purification.
Gas-liquid chromatography (g.I.c.): OV210 at 170* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClj, integral, number of peaks, JHz):
3.70, 2H, d, 10; 3.50, 2H, d, 10; 3.30, 2H, s; 1.20, 6H, s; 0.80, 9H, s.
4- t-Butyl-l-(4-chlorophenyl)-2,6-dioxa-bicyclo (2,2,2] octane was prepared from
5- t-butyl-2,2-dimethyl-5-iodomethyl-l,3-dioxane using the method described for 15 the synthesis of l-(4-chlorophenyl)-4-ethyl-2,6-dioxabicyclo (2,2,2] octane.
Physical Data:- Gas-liquid chromatography (g.I.c):
OV210 at 200* produced one peak.
Melting Point 155 *
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClp integral, number of peaks):
7.25, 4H, m; 4.10, 4H, m; 2.10, 2H, m; 2.00, 2H, m; 1.00, 9H, s.
Infrared spectrum (1R) (nujol mull):
1130 (s), 1100(s), 1015 (s)
Mass spectrum (MS), chemical ionisation:
M+l 281.
Example 5 l-(4-Chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxab»cyclo(2,2,2]octane, and l-(4-Chlorophenyl)-4-ethyl-8-hydroxy-2t6-dioxabicyclo[2,2,2]octane
AP 0 0 0 0 6 6
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2.2- Dimethy!-5-ethyl-5-hydroxymethyl-l,3-dioxane (33g.) was added to a stirred suspension of pyridinium chlorochromate (122.6g) and anhydrous sodium acetate (7.3g.) in dry dichloromethane (200ml.), at 0*, under a current of nitrogen. The mixture was stirred at room temperature for six hours. The mixture was diluted with dry ether (500 ml) and the organic solution was decanted off. The oily residue was treated with ether and the combined extracts were evaporated m vacuo. The residue was purified by chromatography on silica, eluting with ether: hexane 1:3. 2,2-Dimethyl-5-ethyI-5-formyl-l,3-dioxane (30g.) was obtained as a , colourless oil.
> 10
Gas-liquid chromatography (g.l.c.): OV210 at 130* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClp integral, number of peaks, 9.6, lH,s;
4.2, 2H,d,12; 3.8,2H,d,12; 1.4,8H,m; O.85,3H,t,6.
2.2- Dimethyl-5-formyl-5-n-propyl-l,3-dioxane was prepared in an analogous manner from 2,2-dimethyl 5-hydroxymethyI-5-n-propyl-l,3-dioxane.
n-Butyl-lithium (29ml, 1.6M hexane solution) was added to a stirred solution of 4chloro-acetophenone Ν,Ν-dimethylhydrazone (9.0g.) in dry tetrahydrofuran (lOOmls), at -70*, under nitrogen. The mixture was stirred at -70* for 30 minutes. A solution of 2,2-dimethyl-5-formyI-5-n-propyl-l,3-dioxane (9.5g.) in dry tetrahydrofuran (20 mis), at -70* was added. The mixture was allowed to warm up slowly to room temperature and then stirred at room temperature for 5 days.
Water was added and the mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo.
The residue (16g.) and 2N hydrochloric acid (50mls) were stirred at room temperature for 24 hours.
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 silica, eluting with 1:2 ether:hexane. l-(4-Chlorophenyl)-8-hydroxy-4-n-propyl-2,6dioxabicyclo(2,2,2] octane was obtained as a waxy solid (3.5g.)
AJR/EB/2.9.O6 bad original
-21Pll\2
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDClp integral, number of peaks):
Infrared spectrum (1R) (nujol mull):
3470(s and br), 1130 (m), 1100(s), 1030(s).
Mass spectrum (MS), chemical ionisation:
M+l 283 l-(4-Chlorophenyl)-4-ethyl-8-hydroxy-2,6-dioxabicyclo[2,2,2]octane was prepared in a similar manner.
Physical Data
Melting Point 97 *
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDCl-j, integral, number of peaks):
7.35, 4H, m; 4.00, 5H, m; 3.00 - 1.70, 3H, m; 1.30, 2H, m; 0.90, 3H, m.
Infrared spectrum (1R) (nujol mull):
3450 (s and br), 1130 (m), 1100(s), 1080(s), 1020(m).
Mass spectrum (MS), chemical ionisation:
M+l 269
Example 6 l-(4-ChlorophenyI)-8-methoxy-4-n-propyl-2,6-dioxabicyclo[2,2,2)octane n-Butyl-lithium (440ul, 1.6M hexane solution) was added to a stirred solution of l-(4-chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane (200mg.) in dry tetrahydrofuran (lOmls), under a current of nitrogen, at 0·. The mixture was stirred for 30 minutes and methyl iodide (200vl) was added. The mixture was stirred at room temperature, under a current of nitrogen, for 2 days. Water
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-22P7/12 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. The residue was purified by column chromatography on silica, eluting with 1:10 ether:hexane.
l-(4-Chlorophenyl)-8-methoxy-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane was obtained as a colourless solid (66mg.)
U u 1
Nuclear magnetic resonance spectrum (NMR) was as follows: H (ppm from TMS
3-)0 in CDClj, integral, number of peaks):
7.30, 4H, m; 4.40 - 3.40, 5H, m; 3.30, 3H, s; 2.80 - 1.80, 2H, m; 1.50 - 0.80, 7H, m.
Mass spectrum (MS), chemical ionisation:
M+l 297.
Example 7
8-Acetoxy-l-(4-chlorophenyl)-4-n-propyl-2>6-dioxabicyclo[2>2,2)octane
A solution of l-(4-chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxabicyclo[2,2,2)octane (500mg.) and triethylamine (296 ul) in dry ether (20mls) was stirred at 0 ·.
F.
Acetyl chloride (125vl) was added and the mixture was stirred at room temperature for 24 hours. The mixture was poured into water and the aqueous mixture was extracted with diethyl ether. The ethereal extracts was washed with water, dried over anhydrous magnesium sulphate and the solution was evaporated in vacuo. The residue was purified by column chromatography on silica, eluting with 1:6 diethyl ethenhexane.
8-Acetoxy-l-(4-chlorophenyl)-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane was obtained as a waxy solid (lOOrng.).
Nuclear magnetic resonance spectrum (NMR) was as follows: H (ppm from TMS in CDC1.J, integral, number of peaks):
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7.40, 4H, m; 5.20, 1H, d, 8; 4.40-V80, 4H,m; 3.00-2.50, 2H, m; 2.20, 3H, s; 1.400.8, 7H, m.
Mass spectrum (MS), chemical ionisation:
M+l 325.
Example 8 l-(4-Chlorophenyl)-8-oxo-4-n-propyl-2,6-dioxabicyclo[2,2>2)octane.
l-(4-Ch!oropheny l)-8-hy dr oxy-4-n-propy 1-2,6-dioxabicyclo(2,2,2]octane (500mg.) was added to a stirred suspension of pyridinium chlorochromate (955mg.) and anhydrous sodium acetate (270mg.) in dry dichloromethane (20mls.), at 0*, under a current of nitrogen. The mixture was stirred at room temperature for six hours. The mixture was diluted with dry diethyl ether (50mls.) and the organic solution was decanted off. The oily residue was treated with diethyl ether and the combined extracts were evaporated jn vacuo.
The residue was purified by column chromatography on silica, eluting with 1:3 diethyl ether: hexane.
9 0 0 0 0 dV l-(4-Chlorophenyl)-8-oxo-4-n-propyi-2,6-dioxabicyclo(2,2,2)octane was obtained as a colourless solid (240mg.) (m.pt.96*).
Gas-liquid chromatography (g.l.c.):
OV210 at 185* produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDCly integral, number of peaks):
7.40, 4H, m; 4.20, 4H, s; 3.00, 2H, s; 1.50, 4H, m; 1.00, 3H, m.
Infrared spectrum (1R) (nujol mull):
1750(s), 1130(m), 1100(m), 1030,(m), 1010(m).
Mass spectrum (MS), chemical ionisation:
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MU 281
Example 9
1-(4-Chlorophenyl )-4-n-propy I-2,6-di ox abicyclol 2,2,2)oct.-8-yl methanesulphonate
Methanesulphonyl chloride (164vl) was added to a stirred solution of l-(4-chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxabicyclo[2,2,2)octane (500mg.) in dry pyridine (2.0ml.). The mixture was stirred at room temperature for 6 hours. The 10 mixture was poured into water and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with IN hydrochloric acid solution. The ethereal extracts were then washed with saturated aqueous sodium hydrogen carbonate solution. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated m vacuo.
The residue was washed with diethyl ether and the remaining solid was dried in air.
1-(4-Chloropheny 1)-4-n-propyl-2,6-dioxabicyclo[2,2,2Joct-8-ylmethane sulphonate 20 was obtained as a colourless solid (220 mg.)
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from TMS in CDCly integral, number of peaks):
7.40, 4H, m; 5.10, 1H, d, 6; 4.30-3.8, 4H, m; 3.10, 3H, s; 3.00-2.40, 2H, m; 1.50,
4H, m; 1.00, 3H, m.
Mass spectrum (MS), chemical ionisation:
M+l 361
EXAMPLE 10
1-(4-Bromopheny 1)-4-isobuty 1-2,6-dioxa-7-thiabicyclo[2,2,21octane
1) Diethyl isobutylmalonate (22.Og.) was added to a stirred suspension of 35 sodium hydride (4.8g. 50% dispersion in oil) in dry toluene (200ml.), under nitrogen. The mixture was stirred at 80° for one hour. The mixture was cooled and benzyl chloromethyl thioether ^(16.0g.) 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
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Vb ο ο ο ο β e diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated m vacuo. Diethyl 2benzyithiomethyl-2-isobutylmalonate (32.Og.) was obtained as a yellow oil and was used without further purification.
ii) Diethyl 2-benzylthiomethyl-2-isobutylmalonate (32.Og.) in dry diethyl ether (60ml.) was added to a stirred suspension of lithium aluminium hydride (7.0g.) in dry diethyl ether (400 ml.), 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-isobutyl-propan-l,3-diol was obtained as a colourless solid (20g.) and was used without further purification.
iii) 2-Benzylthiomethyl-2-isobutyl-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-4-methylpentan-l-thiol (2.5g.) was obtained as a colourless smelly oil and was used without further purification.
iv) From 2,2-di-hydroxymethyl-4-methyl-pentan-l-thiol (1.2g.) and trimethyl 4-bromo-orthobenzoate using the method described in Example 2 but using one drop of cone.hydrochloric acid as a catalyst in the place of tri ethyl amine, l-(4-bromophenyl)-4-isobuty 1-2,6-dioxa-7-thiabicyclo(2,2,2]octane, a colourless solid, was obtained (90mg.) after recrystallisation from hexane.
In an analogous manner, from 2,2-di-hydroxymethyl-3-methyl-butan-l-thiol or 2,2-di-hydroxymethyl-3-methyi-pentan-l-thiol and trimethyl 4-bromoorthobenzoate or trimethyl 4-chloro-orthobenzoate or trimethyl orthocyclohexyl-carboxylate the following compounds were prepared :-
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-(4-Bromophenyl)-4-_i_-propyl-2,6-dioxa-7-thiabicyclol2,2,2)octane.
l-(4-Bromophenyl)-4-s-buty[-2,6-dioxa-7-thiabicyclo(2.2,2Joctane 1 -(4-ChIorophenyI)-4-s-butyl-2,6-dioxa-7-thiabicycIo(2,2,2Joctane 4-s;-Butyl-l-cyelohe\yl-2,6-dioxa-7-tbiabicyclo[2,2,2]octane
3.3- Di-hydroxymethyl-hexan-2-thiol and 3,3-di-hydroxymethyI-5-methylbexan-2-thiol were prepared by an analogous manner from diethyl npropylmalonate and diethyl isobutylmalonate respectively and benzyl 1chloroethyl thioether^.
3.3- di-hydroxymethyl-hexan-2-thiol or 3,3-di-hydroxy methyl-5-methylhexan-2-thiol were reacted with trimethyl 4-bromo-orthobenzoate*· or trimethyl ortho-cyclohexylcarboxylate^ in an analogous manner to give the following compounds :l-(4-Bromophenyl)-8-methyI-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-Cyclohexyl-8-methyl-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane l-(4-Bromophenyl)-4-i-butyl-8-methyl-2,6-dioxa-7-thiabicyclo(2,2,2]octane.
2,2-di-hydroxymethyl-hexan-l-thiol was prepared in an analogous manner to 2,2-di-hydroxymethyl-4-methyl-pentan-l-thiol starting from diethyl nbutylmalonate.
AP 0 0 0 0 6 6 l-(4-Bromophenyl)-4-n-butyl-2,6-dioxa-7-thiabicyclo(2,2,2]octane (m.pt. 110-112*) was prepared from trimethyl 4-bromo-orthobenzoate and 2,2di-hydroxymethyl-hexan-l-thiol in an analogous manner to the compounds described above.
EXAMPLE 11 l-(4-Bromophenyl)-4-t-butyl-2,6-dioxa-7-thiabicyclo(2,2,2)octane
i) Sodium hydride (1.25g., 50% dispersion in oil) was added to a stirred solution of benzyl mercaptan (3.2ml.) in dry dimethylformamide (75 ml) at 0°, under a current of nitrogen. Stirring was maintained for 30 minutes.
5-t-Butyl-2,2-dimethyl-5-hydroxymethyl-l,3-dioxane methanesulphonate (7.5g.) was added and the mixture was maintained at 130°, with stirring for 7 hours. The reaction mixture was cooled and poured into water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts
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Λ were washed with water, dried over anhydrous magnesium sulphate and then evaporated in vacuo. 5-Benzylthiomethyl-5-t-butyl-2,2-dimethyl-l,3dioxane (7.0g.) was obtained as a mobile oil and was used without further purification.
ii) 5-Benzylthiomethyl-5-t-butyl-2,2-dimethyl-l,3-dioxane (7.0g.) and Dowex 50 x 8-200 ion exchange resin (H+ form) (0.6g.) in methanol (100 ml.) containing water (10ml.) was refluxed, with stirring, for 3 hours. The mixture was filtered and the filtrate was evaporated in vacuo. 2.> Benzylthiomethyl-2-hydroxymethyl-3,3-dimethyl-butan-l-ol was obtained * as a colourless oil (5.0g.) and was used without further purification.
iii) 2-Benzylthiomethyl-2-hydroxymethyl-3,3-dimethyl-butan-l-ol (5.0g.) in dry diethyl ether was added to liquid ammonia (250 ml.) at -70°. Sodium (2.0g.) was added to the stirred solution and stirring was continued for one hour at
-70°. The mixture was allowed to warm up to room temperature, under a current of nitrogen. Solid ammonium chloride (20.Og.) was added. The mixture was filtered and the solid was washed with methanol (100ml.). The filtrates were evaporated jn vacuo. The resulting solid was washed with chloroform (500 ml.). The washings were evaporated in vacuo.
2,2-di-hydroxymethyl-3,3-dimethyl-butan-l-thiol was obtained as a crystalline solid (4.0g.)
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, 3^): 4.00, 4H, s; 3.202.90, 4H, m; 1.90, 1H, t, 7: 1.10, 9H, s.
Mass spectrum (MS), chemical ionisation :
m + 1, 179
From 2,2-di-hydroxymelhyl-3,3-dimethyl-butan-l-thioI and trimethyl 4bromo-orthobenzoate, trimethyl 4-chloro-orthobenzoate, trimethyl ortho35 cyclohexylcarboxylate and trimethyl ortho-cycloheptylcarboxylate in the manner described previously, the following compounds were prepared :l-(4-Bromophenyl)-4-L·butyl-2,6-dioxa-7-thiabicyclo(2,2,2)octane
4-t-Butyl-l-(4-chlorophenyl)-2,6-dioxa-7-thiabicyclo(2,2,2]octane
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4-1.-Butyl -1 -cyclohexyl-2,6-dioxa-7-thiabic ycloi2,2,2]oct ane 4-t-Butyl-l-cycloheptyl-2,6-dtoxa-7-thiabicyclo[2,2,2]octane
EXAMPLE 12
-(4-Chlorophenyl)-4-isobutyl-2-oxa-6,7-dithiabicyclo[2,2,2)octane
i) Methanesulphonyl chloride (26.0ml.) was added dropwise to a stirred solution of 2-benzyloxymethyI-2-hydroxymethyl-4-methyl-pentan-l-ol (prepared from diethyl isobutylmalonate in a manner analogous to that described for the synthesis of 2-benzyloxymethyl-2-cycIohexyl-propan-l,3diol (Example 16)). (41.6g.) and dry pyridine (30ml) in dry diethyl ether (300 ml) at 0°. The mixture was stirred at room temperature for 24 hours and the mixture was poured into water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with IN hydrochloric acid solution, saturated sodium hydrogen carbonate solution and then water. The ethereal extracts were dried over anhydrous magnesium sulphate and evaporated jn vacuo.
The residue was purified by chromatography on silica, eluting with 1:1 diethyl ether : hexane. 2-Benzyloxymethyl 2-hydroxymethyl-4-methylpentan-l-ol di-methanesulphonate was obtained as an oil (23g.).
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, J^^):7.40, 5H, s; 4.60, 2H, s; 4.30, 4H, s; 3.60, 2H, s; 3.10, 6H, s; 2.20-1.00, 9H,
m.
Mass spectrum (MS), chemical ionisation :
m + l, 409.
ii) l-Benzyloxy-2,2-di-benzylthiomethyl-4-methyl-pentane was prepared from
2-benzyloxymethyl-2-hydroxymethyl-4-methyl-pentan-l-ol dimethanesulphonate in a manner analogous to that described for the synthesis of 5-benzylthiomethyl-5-t-butyl-2,2-dimethyl-l,3-dioxane.
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Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, Jj__, ):7.10, 15H, m; 4.40, 2H, s; 3.60, 4H, s; 3.30, 2H, s; 2 9H.
50, 4H, s;
1.80-0.80,
Mass spectrum (MS), chemical ionisation :
m+l, 465
2-i-Butyl-2-hydroxymethyl-propan-l,3-dithiol was prepared from 1benzyloxy-2,2-di-benzylthiomethyl-4-methyl-pentane in a manner analogous to that described for the sysnthesis of 2,2-di-hydroxymethyl-3,3dime thy 1-butan-l-thiol.
1- (4-Chlorophenyl)-4-isobutyl-2-oxa-6,7-di-thia-bicyclo[2,2,21octane was prepared from 2-Rbutyl-2-hydroxymethyl-propan-l,3-dithiol and trimethyl 4-chloro-orthobenzoate in the manner described previously.
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, JHz);7.65, 2H, d, 7; 7.45, 2H, d, 7; 4.25, 2H, s; 3.10, 4H, m; 1.75, 1H, m; 1.30, 2H, d, 6; 1.00, 6H, d, 6.
Mass spectrum (MS), chemical ionisation :
m+l, 315.
2- hydroxymethyl-2-n-propyl-propan-l,3-dithiol was prepared in an analogous manner to 2-Lbutyl-2-hydroxymethyl-propan-l,3-dithiol starting from 2-benzyloxymethyl-2-n-propyl-propan-l,3-diol.
l-(4-Bromophenyl)-4-n-propyl-2-oxa-6,7-dithiabicycIo{2,2,2]octane was prepared from trimethyl 4-bromo-orthobenzoate and 2-hydroxymethyl-2-npropyl-propan-l,3-di thiol.
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Nuclear magnetic resonance spectrum (NMR) was as follows: (p.p.m.
from TMS in CDCl^, integral, number of peaks, J^);
7.50, 4H, m; 4.20, 2H, m; 3.10, 4H, m; 1.35, 4H, m; 0.95, 3H, m.
Mass spectrum (MS), chemical ionisation:
m + 1, 345 347
W EXAMPLE 13 l-Cyclohexyl-4-n-propyl-2,6,7-tri-thia-bicyclo[2,2,2)octane
Starting from 2-hydroxymethyl-2-n-propyl-propan-l,3-diol and using a reaction 15 scheme analogous to that described in example 12 l-cyclohexyl-4-n-propyi2,6,7-tri-thia-bicycio[2,2,2]octane (clear oil) was prepared.
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, J|_| ) :
3.00, 6H, s; 2.00-0.80, 18H, m.
Mass spectrum (MS), chemical ionisation :
m + 1, 289.
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EXAMPLE 14 l-(4-Bromophenyl)-3-methyl-4-n-propyi-2,6-dioxa-7-thiabicyclo[2,2,2)octane
i) 2-Benzylthiomethyl-2-n-propyl-propan-l,3-diol (14.2g.) (prepared from diethyl n-propylmalonate in a manner analogous to that described for the synthesis of 2-benzylthiomethyl-2-isobutyI-propan-l,3-diol (Example 10)) in dry tetrahydrofuran (100 ml.) was stirred at 0°, under a current of nitrogen. Sodium hydride (2.7g, 50% dispersion in oil) was added carefully and the mixture was stirred at 20° for 1 hour. Benzyl bromide (9.6g.) was added carefully and the reaction mixture was refluxed, with stirring for 12 hours. The mixture was cooled and poured into water. The aqueous
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>
«► a
2-Benzyloxymethyl-2-benzylthiomethyl-pentan-l-ol was obtained as a pale yellow oil (22g.) and was used without further purification.
ii) 2-BenzyIoxymethyl-2-benzylthiomethyl-pentan-l-oJ (5g.) was added to a stirred suspension of pyridinium chlorochromate (5g.) and anhydrous sodium acetate (3.0g.) in dry dichloromethane (20ml.) at 0°, under a current of nitrogen. The mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (100 ml.) and the organic solution was decanted off. The oily residue was treated with ether and the combined extracts were evaporated in vacuo. The residue was chromatographed on silica eluting with ethyl acetate : hexane, 1 : 10. 2Benzyloxymethyl-2-benzylthiomethyI-pentanaI was obtained as a colourless oil (1.9g.).
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCly integral, number of peaks) :9.50, 1H, s; 7.30, 10H, s; 4.50, 2H, s; 3.80, 2H, s; 3.65, 2H, s; 2.95, 2H, s; 1.80-0.80, 7H, m.
Infrared spectrum (1R) (liquid film) :
v 1735 cm -1
Mass spectrum (MS),chemical ionisation :
m + 1, 343 iii) Methyl magnesium iodide (4.0ml, 3M solution in ether) was added to a solution of 2-benzyloxymethyl-2-benzylthiomethyl-pentanal (2.6g.) in dry diethyl ether (50ml.) at 0°. The mixture was refluxed, with stirring for 2 hours. The mixture was cooled and poured into IN hydrochloric acid in ice. 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 chromatographed on
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-32P7/12 silica, eluting with diethyl ether. 3-BenzyIoxymethyl-3-benzylthiomethyIhexan-2-ol was obtained as a colourless oil (0.7g.).
Gas-liquid chromatography (g.l.c.) :OV 101 at 250° produced one peak.
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCly integral, number of peaks) :
7.30, 10H, s; 4.40, 2H, m; 4.00-3.00, 6H, m; 2.95-2.40, 2H, m; 1.60-0.70,
10H, m.
Mass spectrum (MS), chemical ionisation :
m + 1, 359.
iv) and v) l-(4-Bromophenyl)-3-methyl-4-n-propyl-2,6-dioxa-7-thiabicyclo(2,2,2]octane (an oil) was prepared from 3-benzyloxymethyl-3-benzyIthiomethyl-hexan-2ol and trimethyl 4-bromo-orthobenzoate using the methodology of stages iii) and iv) of example 10.
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks):
7.40, 4H, s; 4.60-3.90, 3H, m; 3.00, 2H, m; 1.60-0.80, 10H, m.
Mass spectrum (MS), chemical ionisation :
m + 1, 343, 345
Example 15 l-(4-Iodophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane 35 i) n-Butyllithium (16 ml., 1.6M solution in hexane) was added to a stirred solution of l-(4-bromophenyl)-4-n-propyl-2,6-dioxa-7thiabicyclo{2,2,2]octane (1.7g) in dry diethyl ether (150 ml.) at -70*, under nitrogen. The reaction mixture was allowed to warm up slowly to room
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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 (50 ml.) was added and this was followed immediately by the addition of an aqueous solution of sodium thiosulphate (10g. in 70 ml. w-ater'. The mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulphate. The solvent was removed m 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. m.pt. 128-132 *).
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDCl^, integral, number of peaks, J^):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 + l 377
Example 16 l-(4-Cyanophenyl)-4-cyclohexyl-7-methyl-2,6-dioxa-7-aza-bicyclo[2,2,2|octane (i) Diethyl cyciohexylmaionate (18.7g) was added to a stirred suspension of sodium hydride (4.8g. 50% dispersion in oil) in dry tetrahydrofuran (50ml) under nitrogen. The mixture was refluxed, with stirring, for one hour. The mixture was cooled and benzyl chloromethyl ether (13.9g.) in dry tetrahydrafuran (50ml) was added and the mixture was refluxed, with stirring, for three hours. The mixture was cooled and poured into water.
The aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Diethyl 2-benzyloxymethyl-2-cyclohexyl-malonate (30g.) was obtained as a brown oil and was used without further 40 purification.
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-34P7/12 (ii) Diethyl 2-benzyloxymethyi-2-cyclohexyl-malonate (2g.) was added to a suspension of lithium aluminium hydride (0.63g? in dry ether (30ml), at 0*, under nitrogen. The mixture was stirred at room temperature for twelve hours. Water (5 ml) was added carefully and the mixture was stirred for ten minutes. 10% sulphuric acid solution (10ml) was added and the mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated jn vacuo. The residue was purified by chromatography on silica, eluting with 1:1 ether: hexane. 2-8enzyloxymethyl-2-cyclohexyl-propan-l,3-diol was obtained as a colourless oil (l.Og.).
Gas-liquid chromatography (g.l.c.): OV210 at 230 * produced one peak.
AP 0 0 0 0 6 6
Nuclear magnetic resonance spectrum (NMR) was as follows: (ppm from
TMS in CDCl-j, integral, number of peaks, J^):
iii)
7.35,5H,s; 4.55,2H,s; 3.75,4H,d,6; 3.60,2H,s; 2.90,2H,t,6; 2.00-0.90, llH,m.
2-Benzyloxymethyl-2-cyclohexyl-propan-l,3-diol (5.5g.) in dry diethyl ether (50ml.) was added to liquid ammonia (200ml) 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 0 * and solid ammonium chloride (15g.) was added cautiously. The ammonia was removed from the reaction mixture under a current of nitrogen. Methanol (25ml.) was added to the stirred mixture to destroy residual sodium. Dichloromethane (400ml) was added and the mixture was filtered. The filtrates were evaporated in vacuo. 2-Cyclohexyl-2-hydroxymethyl-propan-l,3-dioI was obtained as a colourless solid (3.2g.).
Nuclear magnetic resonance spectrum (NMR) was as follows : (ppm from TMS in CDCly integral, number of peaks) :
3.80,6H,s; 3.30,3H,s; 2.00-0.80. IlH,m.
iv) A mixture of 2-cyclohexyl-2-hydroxymethylpropane-l,3-diol (3.76g), ethyl carbonate (2.42 ml) and a solution of potassium hydroxide in ethanol (0.1 ml
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of a solution of 5g in 25 ml) were refluxed for 20 minutes. The apparatus was converted to distillation. Ethanol was removed by distillation (7880 *C at 760 mmHg). When all the ethanol had been removed the residue was distilled at reduced pressure, 3-cyclohexyl-3-hydroxymethyloxetane distilled as a colourless oil.
Nuclear magnetic resonance spectrum (NMR) was as follows : (p.p.m.
from TMS in CDClp integral, number of peaks, JHz):_
4.50, 4H, s; 3.75, 2H, d, 6; 2.6, 1H, t,6; 2.00-1.00, 11H, m.
Infrared spectrum (IR) liquid film:
3400 (s and br), 1150(s), 970(s),
Mass spectrum (MS) , chemical ionisation:
m + 1 171.
v) 3-Cyclohexyl-3-hydroxymethyloxetane (7.0g) was dissolved in dry dichloromethane (20ml) and added dropwise to a mixture of oxalyl chloride (1.1 eq, 4 ml) in dry dichloromethane (15 ml). At -70 *C a solution of dimethyl sulphoxide (7.15 ml) in dichloromethane (10ml) was added. After stirring at -70 *C for 30 minutes triethylamine (29 ml) was added over 30 minutes. The reaction mixture was allowed to warm up to room temperature over a period of 3 hours and then quenched in water.
Extraction with dichloromethane, followed by washing with dilute hydrochloric acid, saturated sodium bicarbonate solution and brine and drying over magnesium sulphate gave a solution which was evaporated to give 3-cyclohexyl-3-formyloxetane as a colourless oil.
Nuclear magnetic resonance spectrum (NMR) was as follows : m (p.p.m. from TMS in CDClp integral, number of peaks, J^):
9.80, 1H, s; 4.68, 2H, d, 6; 4.50, 2H, d, 6; 2.05-1.00, 11H, m.
Infrared spectrum (IR) liquid film
172O(s), 980(s).
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-36P7/12 vi) 3-Cyclohexyl-3-formyloxet.ane (1.7g) was dissolved in rnettiano! (10 ml) at 25 *C. In -succession, anhydrous sodium acetate (3.3g), methylamine hydrochloride (3.4g) and sodium cyanoborohydride (630 mg) were added, followed by a further volume of methanol (30 ml). The mixture was stirred overnight and then basified with sodium hydroxide solution (1M, 22 ml) to pH9. Ether extraction, washing and drying, followed by evaporation gave
3-cyclohexyl-3-methylaminomethyloxetane as a colourless oil.
Nuclear magnetic resonance spectrum (NMR) was as follows :- (p.p.m. from
TMS in CDClp integral, number of peaks, Jf_jz):
4.49, 2H, d, 5; 4.35, 2H, d, 5; 2.75, 2H, s; 2.50, 3H, s; 2.05-1.10, m, (11H).
Infrared spectrum (IR) liquid film
3300(w) and (br), 9S0(s).
Mass spectrum (MS), chemical ionisation:
M + l 184
AP 0 0 0 0 6 6 vii) 4-Cyanobenzoyl chloride (0.166g) in dichloromethane (5 ml) was added to a stirred solution of 3-cyclohexyl-3-methylaminomethyl oxetane (0.183g) and triethylamine (0.42ml) in dichloromethane (5 ml) at 0*C. After stirring overnight the reaction mixture was poured into saturated sodium bicarbonate solution. Extraction with ether gave crude product which was purified by chromatography on alumina, eluting with dichloromethane:hexane (1:1) saturated with ammonia.
3-[N-(4-Cyanobenzoyl)-N-methylaminomethyl]-3-cycIohexyloxetane was obtained as a colourless oil.
Nuclear magnetic resonance spectrum (NMR) was as follows :- (p.p.m.
from TMS in CDClj, integral, number of peaks, J^z):
7.75, 2H, d, 8; 7.50, 2H, d, 8; 4.54, 4H, 5; 3.73, 2H, s; 3.09, 3H, s; 2.05-0.95,
11H, m.
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-37P7,'i 2
Infrared spectrum (IR) liquid film
222O(s) 1640(s) 1070(m) 980lm)
Mass spectrum (MS), chemical ionisation;
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M + 1 313 viii) Boron trifluoride etherate (37.2 ul) was added to a stirred solution of 3-(N(4-cyanobenzoyl)-N-methylaminomethyl]-3-cycIohexyloxetane (281 mg) in dichloromethane (3 ml) at -70 *C under nitrogen. After stirring overnight a further portion of boron trifluoride etherate (110 ul) was added. After stirring for a further 24 hours the reaction mixture was poured into dichloromethane (20 ml, saturated with ammonia). Filtration and evaporation of the filtrate gave l-(4-cyanophenyl)-4-cyclohexyl-7-methyl2,6-dioxa-7-aza-bicyclo[2,2,2]octane as pale yellow crystals.
Nuclear Magnetic resonance spectrum (NMR) was as follows :- (ppm from TMS in CDCly integral, number of peaks).
7.60, 4H, s; 3.95, 4H, s; 2.95, 2H, s; 2.04, 3H, s, 1.90-1.00, 11H, m.
Infrared Spectrum (IR) (nujol mull):
2220(s) 1140(m) 1080(s) 1030(m) 990(m)
Mass spectrum (MS), chemical ionisation:
M + 1 313.
AJR/EB/2.9.86
BAD ORIGINAL ft
- 3SP7/12
References :1. V.Gash
J.Org.Chem. 197 2,37,2197 5 la. W.E.Conrad, L.A.Levasseur, R.F.Murphy N.L.Hare and H.E.Conrad J.Org.Chem,1962,27,2227
2. 5.M.McElvain and J.T.Venerable
J.Amer.Chem.Soc.1950,72,1661
3. S.M.McElvain and R.E.Starn J.Amer.Chem.Soc.1955,77,4571
4. Y.Ozoe and M.Eto,
Agric.Biol.Chem.1982,46,411
5. J. L. Wood and V. du Vigneaud
2C J. Biol. Chem. 1939, 131, 267
6. I. Vlattas, L. D. Vecchia and J.J. Fitt J. Org. chem. 1973, 38, 3749
Characterising data for various compounds of the invention are set out in the Table below.
APO00066
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X ω 3 jpAf ORIGINAL $
-41P7/12
i) BIOLOGICAL ACTIVITY '3
A. Lethal Activity Against Houseflies
The activity of compounds of the invention against unanaesthatised 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 conjunction with the synergist piperonyl butoxide (6ug PB per insect). Mortality was assessed after 24 and 48 hours.
The following compounds were active at less than 30 vg/fly:
2,3,6,8,11,14,17,18,19,20,23,27,29,30
The following compounds were active at less than 1 vg/fly:
4,13,15,21,22,24,25,28
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 (lOvg PB per insect). Mortality was assessed after 24 and 48 hours.
The following compounds were active at less than 50 vg/insect:
2,3,8,9,14,15,17,18,19,20,21,22,23
The following compounds were active at less than 5 vg/insect:
4, 13
AJR/EB/2.9.86
BAD ORIGINAL
-42P7/1
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 :
4,15,16,17,18,19,20,21,22,23,27,29,30
AP 0 0 0 0 6 6
The following comnpounds gave activity at less than 50 ppm solution of acetone:
13,14,25
D. Lethal activity against Culex quinquefasciatus
The activity of the compounds of the invention against female Culex adults were 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%:
4,5,13,14,15,16,19,21,22,25,27,28,30
E. Mammalian Toxicity
Compound 4 has an LD^q of greater than 200mg/kg when given orally to mice (Charles River CD1).
AJR/EB/2.9.86 bad original
I
-4}P?/l 2
Pie following schemes serve to illustrate the preparation of intermediates used in the preparation of compounds of the present invention.
Aik ; alkyl, R, r \ PP etc are as defined in the specification :
3*
X?
o
SCHEME 1
(i) MeCOSH,NaH,DME (ii) NaOH, MeOH, H2O (iii) Dowex 50 x 8-200, MeOH, H2O
AJR/EB/2.9.86
BAD ORIGINAL $
-4uP7/12
AlkO
AP 0 0 0 0 6 6
BAD ORIGINAL
AJR/EB/2.9.86
Ρ7/12
Vb?o ο ο ο e β
SCHEME 3
(i) | (EtO)2CO, KOH, EtOH | (ii) | ( COCI)2,DMSO,Et^N |
(iii) | NH2R5, NaCNBH^, MeOH | ( iv) | R2COC1 Et3N, CH2C12 |
(v) | BF3,Et20,CH2C12 |
SCHEME 4
1e
. . ., ,..., MeCR , nBu-Li (i) MeSO Cl, pyridine (ii) Nal, EtCOMe (m) u NNMe2 (iv) NaH, PhCH^SH, DMF (v) H* ion exchange resin (vi) NatmH, AJR/EB/2.9.86
HO HO SH BAD ORIGINAL £
-46P7/12
SCHEME 5
(ii) PCC, CH3CO2NB,CH2C12
i) NaH,THT,PhCH2Br
MgI,Et20 (iv) Na.l.VH
AP 0 0 0 0 6 6
(i) MeS02Cl, pyridine (ii) PhCH2SH,NaH,DMF (iii) Na,NH3
BAD ORIGINAL d
AJR/EB/2.9.86
-47P7/12 o
o *·*-., jj >
CHO
BF3 0Et2 CH2C12
MeSO^Cl <
Pyridine
S
AJR/EB/2.9.86 c
BAD ORIGINAL
-48P7/12
NaH
Benzene
Aik
Ph MeSO^ MeSO
K SCOMe Dmf
PhCH^OCH?CHo X
Pyridine
MeSO?Cl
J L‘
Ph aih
NaOH
Me Me
AP 0 0 0 0 6 6 x - leaving group such as halogen (i) (CH3)3SiI R (ii)(n-Bu) F 4
OH
AJR/EB/2.9.86
BAD ORIGINAL ft
-49P7/12
F ormulationg
1. Emulsifiable Concentrate
5 | Compound of formula (1) Ethylan KEO Xylene | 10.00 20.00 67.50 | |
Butylated Hydroxyanisole | 2.50 | ||
o | 10 | 100.00 | |
2. Wettable Powder | |||
15 | Compound of formula (I) | 25.0 | |
Attapulgite | 69.50 | ||
Sodium isopropylbenzene sulphonate Sodium salt of condensed naphthalene | 0.50 | ||
sulphonic acid | 2.50 | ||
20 | Butylated hydroxytoluene | 2.50 | |
100.00 |
25 | 3. Dust | |
Compound of formula (I) | 0.50 | |
Butylated Hydroxyanisole | 0.10 | |
30 | T ale | 99.40 |
100.00
BAD ORIGINAL &
AJR/EB/2.9.86
-50P7/1 2
4. Bait
5 | Compound of formula (I) Icing Sugar Butylated hydroxy toluene | 40.25 59.65 0.10 |
100.00 |
10 | 5. Lacquer | |
Compound of formula (I) | 2.5 | |
Resin | 5.0 | |
Butylated Hydroxy anisole | 0.5 | |
15 | High aromatic white spirit | 92.0 |
100.00 |
APO00066
20 | 6. Aerosol | |
Compound of formula (I) | 0.30 | |
Butylated Hydroxy anisole | 0.10 | |
1,1,1 -T richloroethane | 4.00 | |
25 | Odourless Kerosene | 15.60 |
Arcton 11/12. 50:50 mix | 80.00 |
100.00
30 | 7. Spray | |
Compound of formula (I) | 0.1 | |
Butylated Hydroxy anisole | 0.1 | |
Xylene | 10.0 | |
35 | Odourless Kerosene | 89.8 |
100.00
AJR/EB/2.9.86 bad ORIGINAL
-51P7/12
8. Potentiated Spray
Compound of formula (1) 0.1
Piperonyl Butoxide 0.5
Butylated Hydroxy anisole 0·1
Xylene 10.1
Odourless Kerosene 89.2
99000 ORA
100.0
AJR/EB/2.9.86
BAD ORIGINAL 0
- X
P7/12
Claims (9)
- Ci.Λ I MO1. A compound of the formula (I):AP000066 wherein R is C2-1O alkenyl or alkynyl, each optionally substituted by, or methyl substituted by, cyano, C^_4 cycloalkyl, halo, C^_4 alkoxy, or a group S(O) R4 where R4 is C. . alkyl and m is 0, 1 or 2, or R isC.j_i0 cycloalkyl, cycloalkenyl or phenyl, each optionally substituted by C^_4 alkoxy, Cj_3 alkyl, C2_4 alkynyl, halo, cyano or a group SiOJ^R4 as defined hereinbefore;1 4 4R is hydrogen, halo, a group COOR where R is C^_4 alkyl, alkyl, C2_^ alkenyl or alkynyl, the alkyl, alkenyl or alkynyl each being optionally substituted by halo, cyano or C, . alkoxy; alkyl carbalkoxy containing 4 up to 6 carbon atoms, a group S(0) R as defined 1 m hereinbefore, or R is cyano, gem-dimethyl, spiro-cyclopropyl, gem-dicyano, gem-diethynyl, oxo or methylene optionally substituted by cyano or CF, or R^ is 1C2_3 alkynyl substituted by tr i-C^^-al kylsilyl or R and R and the carbon atoms to which they are attached form a C5_7 carbocyclic ring optionally substituted by halo, C^-j alkyl or alkoxy or C9 -> alkenyl;
- 2 . 3R is phenyl, C^_jq cycloalkyl or cycloalkenyl optionally substituted;R^ is hydrogen, alkyl, C2-3 alkenyl or alkynyl each optionally substituted by cyano, Cj_4 alkylthio, Cj_4 alkoxy or halo or cyano or halo;BAD ORIGINAL- /S3P7/12Y and yl are the same or different and are each selected from oxygen and S (0) where m is 0, 1 or 2;Z is CH2CH^, CH2CH20, sulphur, CH20, CH2S, CHRiXNR wherein R1 is hydrogen, cyano, halo, a group CO2R or5 alkyl, C2_3 alkenyl or alkynyl each optionally substituted by halo, cyano, C._. alkoxy, alkyl carbalkoxy A ** 4 containing up to 6 carbon atoms or a group S (0) R wherein4 5 m m and R are as hereinbefore defined and R is hydrogen, benzyl, C^_4 alkyl, C(0)R^ wherein R^ is Cj_4 alkyl, alkoxy or a group NHR^ wherein R^ is C^_4 alkyl, C^_ aralkyl or phenyl optionally substituted by halo or Z isQ Q-CO.CH2~ or -CH(OR )CH2~ wherein R is hydrogen, C^_4 alkyl, C1-4 acyl or C9_7 carbamoyl or a group S09RH wherej. - η c -! - ' tR is C|_4 alkyl, the first-mentioned atom in the definition of Z being adjacent to the 4-position of the bicyclic ring system;with the proviso that (i) when Z is CHR^XNR^, then R^ and must be hydrogen, (ii) when Y and are both 0, then Z is not CH_0 and 2 (iii) R is not phenyl substituted by an optionally substituted C2_^ alkynyl group.2. A compound according to claim 1 in which R is n-propyl, n-butyl, i-butyl, t-butyl, or cyclohexyl.in which RA compound according to either claim 1 or 2 is hydrogen, methyl, or trifluoromethyl.4. A compound according to any one of the 2 preceding claims wherein R is phenyl, cyclohexyl or cycloheptyl optionally substituted at positions 3, 430 and/or 5 by at least one chloro, bromo, iodo, cyano, azido 2 or nitro group or R is phenyl substituted at position 2 and/or 6 by fluoro.SET BBAD ORIGINAL SP7/12 preced ing5. A compound according to any one of claims wherein is hydrogen or methyl the6. A compound according to any one of the preceding claims wherein Y is 0, Y is 0 and Z is CH20 or ch2s .7. A compound of the formula IA:(IA) wherein R is C2_7 alkyl, alkenyl or alkynyl, each optionally substituted by cyano, halogen or C1-4 alkoxy,10 or Ra is cycloalkyl, cycloalkenyl or phenyl, each optionally substituted by C^_4, alkoxy, C^_3 alkyl, C^_4 alkynyl, halogen or cyano;Ria is hydrogen, C^_3 alkyl, C2_3 alkenyl or alkynyl each optionally substituted by cyano, C|_4 alkoxy, Cj_415 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 carbocyclic ring optionally substituted by C^_3 alkyl, or alkoxy;20 R2a is phenyl, Cg_1g cyaloalkyl or cycloalkenyl, each optionally substituted;and R^a is hydrogen, C^_3 alkyl, C2-3 axkenΪx or alkynyl each optionally substituted by cyano, C^_4 alkylthio, C^_4 alkoxy or halo;25 Ya and Y^a are the same or different and are each selected from oxygen or S(O)m a where ma is 0, 1 or 2;Za is CH2CH2, CH2CH20, sulphur, CH20, CH2S or CH2NR4aSET BBAD ORIGINALΡ 7/1 24a5a wherein R wherein R -CH(OR6a)CH .53 is hydrogen, benzyl, C^_^ alkyl, C(0)R is alkyl or alkoxy, or Z is -CO.Ct^- or- wherein R6a 2 .> is hydrogen, C,_4 alkyl, or C^_4 acyl with the proviso that when Ya and Yia are both α>
- 3» οο οο-Q >5 oxygen, then Z* is not Ο^θ·8. 1- (4-bromophenyl) -4-_i-buty 1-2,6-dioxa-7thiabicyclo[2,2,2] octane;1- (4-bromophenyl)-4- i-propyl-2,6-dioxa-7-thiabicyclo[2.2.2] octane;10 1- (4-bromophenyl)-4-s-butyl-2,6-dioxa-7-thiabicyclo[2.2.2] octane;1-(4-chlorophenyl)-4-s-buty1-2,6-dioxa-7-thiabicyclo[2.2.2] oc tane;
- 4-s-buty1-1-eyelohexyl-2,6-dioxa-7-thiabicyclo[2,2,2 ] 15 octane;1- (4-bromopheny1)-3-methy1-4-n-propyl-2,6-dioxa-7thiabycyclo[2,2,2]octane;1-cyclohexyl-5-n-propyl-2,7,8-triobicyclo(2,2,2 ] nonane;20 1- (4-chlorophenyl)-4-n-propy1-2,6-dioxabicyclo[2.2.2] oc tane;1-(4-bromophenyl)-4-n-propy1-2,6-dioxa-7-thiabicyclo[2.2.2] octane;4-t-butyl-1-(4-chlorophenyl)-2,6-dioxabicyclo25 [ 2,2,2]octane;1- (4-chlorophenyl)-8-hydroxy-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane;1-(4-chlorophenyl)-8-methoxy-4-n-propy1-2,6-dioxabicyclo[2,2,2]octane;30 1- (4-chlorophenyl)-8-oxo-4-n-propyl-2,6-dioxabicyclo[2,2,2]octane;1-(4-bromophenyl)-4-t-butyl-2,6-dioxa-7-thiabicyclo[2,2,2]octane;SET BBAD ORIGINAL &S”G - 5 4-t-butyl-1-(4-chloropheny1)-2,6-dioxa-7-thiabicyclo[2,2,2]octane;l-(4-iodophenyl)-4-n-propyl-2,6-dioxa-7-thiabicyclo[ 2,2,2]octane;
- 5 4-t-butyl-l-cyclohexyl-2,
- 6-dioxa-7-thiabicyclo[2,2,2]octane;4-t.-buty 1-1-cyclohepty 1-2,6-dioxa-7-thiabicyclo[2.2.2] octane;l-(4-chlorophenyl) -4-j-butyl-2-oxa-6,7-dithiabicyclo10 (2,2,2]oc tane;1-eyelohe xyl-4-n-propy1-2,6,7-trithiabicyclo[2,2,2]octane;l-cyclohexyl-8-methyl-4-n-prooyl-2,6,-dioxa-7thiabicyclo[2,2,2]-octane;15 1- (4-bromophenyl) -4-_i-butyl-8-methy 1-2, 6-dioxa-7th iabicyclo-[2,2,2]octane;1-(4-bromophenyl)-8-methyl-4-n-propyl-2,6-dioxa-7thiabicyclo-[2,2,2]octane;1- (4-bromophenyl)-4-n-butyl-2,6-dioxa-7-thiabicyclo20 [2,2,2]octane;1-(4-bromophenyl)-4-n-propyl-2-oxa-6,7-dithiabicyclo[2.2.2] octane.P7/1 2APO000669. A process for the preparation of a compound as defined in any one of claims 1 to 8 wherein X contains
25 a hetero atom which comprises condensing an orthocarboxylate of the formula R C9OR )-. with a compound of formula II: R (II) J2 3 y H SET BBAD ORIGINAL dP7/1 2 xΟΟ οΛ12 3 where R, R , R and R are as defined in any one of claims9 21 to 7, R is alkyl, phenyl or C7_g aralkyl, Y andY3, which are the same or different are each 0 or S and Z is a group CH2CH2OH, SH, CH2OH, CH2SH or CHRlxNHR5 where5 R^X and R8 are as defined in claim 1, with the proviso - 7 3 1 that Y and Y are not both 0 when Z is CH2OH.10. A process for the preparation of a compound of formula I as defined in any one of claims 1 to 8 wherein Z is CH2CH2 and Y and Y^ are both 0 which10 comprises deprotecting and cyclising a compound of formula III:where R, and R2 are as defined in claim 1, is a hydroxy protecting group and R1 is a C^_4 alkyl group.15 11. A process for the preparation of a compound of formula I as defined in any one of claims 1 to 8 wherein Z is CH(OR8)CH2 and Y and Y1 are both 0 which comprises deprotecting and cyclising a compound of formula IIIA:SET BBAD ORIGINALP7/1 2 wherein R, and R2 are as defined inclaim 1, is a hydroxy protecting group and R11 is a Cy_4 alkyl group to give a compound of formula I having an 8-OH substituentQ and converting the 8-OH group to an 8-OR group.12. A process for the preparation of a compound of formula I as defined in any one of claims 1 to1 3 6
- 8 wherein Y and Y are each 0 and Z is CHjR NHR which comprises cyclisation of a compound of formula IV:(rv)AP0000662 3 5 where R, R , R and R are as defined in claim 1 in the presence of an acid catalyst.l'3'Γ A process according to any one of claims 9 to 12 substantially as thereinbefore described with reference to any one jzff Examples 1 to 16.z14.A compound of formula I as defined in any one of claims 1 to 8 whenver obtained by a process according to any one of claims 9 to Γ3.. An insecticidal or acaricidal composition comprising a compound^of formula (I) as defined in any one of claims 1 to 8 or d/4 in admixture with a carrier or d iluent./>1<.A synergised pesticidal composition comprising a compound of^formula (I), as defined in any one of claims 1 to 8 or χί'4, a synergist for the formula I25 compound and a carrier or diluent.bad ORIGINAL d-/P7/1 2 σι a f» c ο η o qA17. A mixture of a compound of formula (I) as defined in any one of claims 1 to 8 or 14 and another pesticidal compound.18.isition/or mixture according to any one of claims 15 to 17 sul described with reference 1 to 8.mtially as hereinbefore to any otr<of Formulations1/9. A method for the control of pests compcising application to the pest or to an environment10 susceptible to pest infestatio^n of a compound according to any one of claims 1 to 8 or JL4 or a composition or mixture according to any one of claims 15 to 18.20. A compound of the formula:(11) or (III)SET BBAD originalP7/1 (IV) or bo2 3 claims 1 tc 9, Y and Y , which may be the same or different, is each 0 or S, Z1 is -CH?CH?OH, -SH, -CH?OH,-CH-SH or -CHRiXNHK where RiX and ϊν are as defined in z 10 any one of claims 1 to 9, R is a hydroxy protecting group and is a Cl_d alkyl group; and Q is H or OH, with the provisos that in formula II ch2oh,1 2 (1) Y and Y are not both 0 when is 2 3 (2) when Y and Y are each 0, Z·^ is -CH2SH and R1 and R3 are each hydrogen, then R is not alkyl or substituted alkyl. ·
- 9 9 l· (3) when Y and Y are each X, Z^ is —CH2SH and R and R·* are each hydrogen, then R is not methyl.19. A compound according to claim 18 of 2 3 formula II wherein Y and Y are both S and Z^ is -Cli2OH20,A compound according to claim 18 of2 3 formula II wherein Y and Y are both S and Z^ is -CH2SH.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB858523582A GB8523582D0 (en) | 1985-09-24 | 1985-09-24 | Insecticidal compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
AP8600046A0 AP8600046A0 (en) | 1986-08-01 |
AP66A true AP66A (en) | 1989-12-12 |
Family
ID=10585663
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
APAP/P/1986/000046A AP66A (en) | 1985-09-24 | 1986-09-22 | Pestcidal compounds. |
Country Status (5)
Country | Link |
---|---|
JP (1) | JPS62116585A (en) |
AP (1) | AP66A (en) |
DD (2) | DD260499A5 (en) |
GB (1) | GB8523582D0 (en) |
ZA (1) | ZA867209B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AP1324A (en) * | 1999-08-13 | 2004-11-12 | Nampak Products Ltd | A blank from which a box can be erected. |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1399167A (en) * | 1971-12-22 | 1975-06-25 | Bayer Ag | 2-alkyl-2-mercaptomethyl-1,3-propane diols |
EP0152229A2 (en) * | 1984-01-30 | 1985-08-21 | The Regents Of The University Of California | A class of pesticides comprising 1,4-bis-substituted-2,6,7-trioxabicyclo(2.2.2)octanes |
-
1985
- 1985-09-24 GB GB858523582A patent/GB8523582D0/en active Pending
-
1986
- 1986-09-22 JP JP61224075A patent/JPS62116585A/en active Pending
- 1986-09-22 DD DD86294594A patent/DD260499A5/en not_active IP Right Cessation
- 1986-09-22 ZA ZA867209A patent/ZA867209B/en unknown
- 1986-09-22 AP APAP/P/1986/000046A patent/AP66A/en active
-
1988
- 1988-09-22 DD DD88319780A patent/DD282388A5/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1399167A (en) * | 1971-12-22 | 1975-06-25 | Bayer Ag | 2-alkyl-2-mercaptomethyl-1,3-propane diols |
EP0152229A2 (en) * | 1984-01-30 | 1985-08-21 | The Regents Of The University Of California | A class of pesticides comprising 1,4-bis-substituted-2,6,7-trioxabicyclo(2.2.2)octanes |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AP1324A (en) * | 1999-08-13 | 2004-11-12 | Nampak Products Ltd | A blank from which a box can be erected. |
Also Published As
Publication number | Publication date |
---|---|
GB8523582D0 (en) | 1985-10-30 |
JPS62116585A (en) | 1987-05-28 |
DD282388A5 (en) | 1990-09-12 |
DD260499A5 (en) | 1988-09-28 |
AP8600046A0 (en) | 1986-08-01 |
ZA867209B (en) | 1987-05-27 |
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