NO153098B - 3-SUBSTITUTED 2,2-DIMETHYL-CYCLOPROPANCARBOXYL ACIDES AND LOWER ALKYLESTERS THEREOF USE AS OUTSIDE MATERIALS IN THE PREPARATION OF PYRETHROIDS WITH INSECTICID EFFECT - Google Patents
3-SUBSTITUTED 2,2-DIMETHYL-CYCLOPROPANCARBOXYL ACIDES AND LOWER ALKYLESTERS THEREOF USE AS OUTSIDE MATERIALS IN THE PREPARATION OF PYRETHROIDS WITH INSECTICID EFFECT Download PDFInfo
- Publication number
- NO153098B NO153098B NO792716A NO792716A NO153098B NO 153098 B NO153098 B NO 153098B NO 792716 A NO792716 A NO 792716A NO 792716 A NO792716 A NO 792716A NO 153098 B NO153098 B NO 153098B
- Authority
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- Norway
- Prior art keywords
- dimethyl
- hydrogen
- reaction
- acid
- compound
- Prior art date
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- VEMKTZHHVJILDY-UXHICEINSA-N bioresmethrin Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OCC1=COC(CC=2C=CC=CC=2)=C1 VEMKTZHHVJILDY-UXHICEINSA-N 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 15
- 230000000694 effects Effects 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 239000000460 chlorine Chemical group 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 15
- 229920002554 vinyl polymer Polymers 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- -1 3-substituted 2,2-dimethyl-cyclopropanecarboxylic acids Chemical class 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 230000000749 insecticidal effect Effects 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 5
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 2
- 101150065749 Churc1 gene Proteins 0.000 claims 2
- 102100038239 Protein Churchill Human genes 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000243 solution Substances 0.000 description 25
- 125000004494 ethyl ester group Chemical group 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 238000001816 cooling Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- 239000013067 intermediate product Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 238000004817 gas chromatography Methods 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
- BFNMOMYTTGHNGJ-UHFFFAOYSA-N 2,2-dimethylcyclopropane-1-carboxylic acid Chemical class CC1(C)CC1C(O)=O BFNMOMYTTGHNGJ-UHFFFAOYSA-N 0.000 description 5
- FYYOTZLMLLTWAP-UHFFFAOYSA-N 3,3-dimethylpent-4-enoic acid Chemical compound C=CC(C)(C)CC(O)=O FYYOTZLMLLTWAP-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 240000004460 Tanacetum coccineum Species 0.000 description 4
- ROVGZAWFACYCSP-MQBLHHJJSA-N [2-methyl-4-oxo-3-[(2z)-penta-2,4-dienyl]cyclopent-2-en-1-yl] (1r,3r)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate Chemical compound CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)OC1C(C)=C(C\C=C/C=C)C(=O)C1 ROVGZAWFACYCSP-MQBLHHJJSA-N 0.000 description 4
- FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 4
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 4
- ZQMIGQNCOMNODD-UHFFFAOYSA-N diacetyl peroxide Chemical compound CC(=O)OOC(C)=O ZQMIGQNCOMNODD-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229940015367 pyrethrum Drugs 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 229910052727 yttrium Inorganic materials 0.000 description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 3
- KECJPTAJLDCQHM-UHFFFAOYSA-N 3-chloro-3-methylbut-1-ene Chemical compound CC(C)(Cl)C=C KECJPTAJLDCQHM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- CINBGMPCJVKMPZ-UHFFFAOYSA-N ethyl 4,6,6-tribromo-7,7,7-trifluoro-3,3-dimethylheptanoate Chemical compound CCOC(=O)CC(C)(C)C(Br)CC(Br)(Br)C(F)(F)F CINBGMPCJVKMPZ-UHFFFAOYSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- WXRPTWOZORWLQE-UHFFFAOYSA-N 3-(2-chloro-3,3,3-trifluoropropyl)-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)C(CC(Cl)C(F)(F)F)C1C(O)=O WXRPTWOZORWLQE-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000001879 copper Chemical class 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- AMIBLBGLTDBYJJ-UHFFFAOYSA-N ethyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate Chemical compound CCOC(=O)CC(C)(C)C(Cl)CC(Cl)(Cl)C(F)(F)F AMIBLBGLTDBYJJ-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000002917 insecticide Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- 150000001451 organic peroxides Chemical class 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- WXRPTWOZORWLQE-NOWQFEBASA-N (1s,3s)-3-(2-chloro-3,3,3-trifluoropropyl)-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)[C@@H](CC(Cl)C(F)(F)F)[C@@H]1C(O)=O WXRPTWOZORWLQE-NOWQFEBASA-N 0.000 description 1
- CALRXIQBQWFLRG-UHFFFAOYSA-N 1,1,1-tribromo-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Br)(Br)Br CALRXIQBQWFLRG-UHFFFAOYSA-N 0.000 description 1
- BOSAWIQFTJIYIS-UHFFFAOYSA-N 1,1,1-trichloro-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Cl)(Cl)Cl BOSAWIQFTJIYIS-UHFFFAOYSA-N 0.000 description 1
- JLGADZLAECENGR-UHFFFAOYSA-N 1,1-dibromo-1,2,2,2-tetrafluoroethane Chemical compound FC(F)(F)C(F)(Br)Br JLGADZLAECENGR-UHFFFAOYSA-N 0.000 description 1
- ZMFVOZUJGHVPDM-UHFFFAOYSA-N 4,6-dibromo-6,7,7,7-tetrafluoro-3,3-dimethylheptanoic acid Chemical compound CC(C)(CC(O)=O)C(Br)CC(F)(Br)C(F)(F)F ZMFVOZUJGHVPDM-UHFFFAOYSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- XLOPRKKSAJMMEW-SFYZADRCSA-N Chrysanthemic acid Natural products CC(C)=C[C@@H]1[C@@H](C(O)=O)C1(C)C XLOPRKKSAJMMEW-SFYZADRCSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000032826 Ring chromosome 3 syndrome Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- VXSIXFKKSNGRRO-MXOVTSAMSA-N [(1s)-2-methyl-4-oxo-3-[(2z)-penta-2,4-dienyl]cyclopent-2-en-1-yl] (1r,3r)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate;[(1s)-2-methyl-4-oxo-3-[(2z)-penta-2,4-dienyl]cyclopent-2-en-1-yl] (1r,3r)-3-[(e)-3-methoxy-2-methyl-3-oxoprop-1-enyl Chemical class CC1(C)[C@H](C=C(C)C)[C@H]1C(=O)O[C@@H]1C(C)=C(C\C=C/C=C)C(=O)C1.CC1(C)[C@H](/C=C(\C)C(=O)OC)[C@H]1C(=O)O[C@@H]1C(C)=C(C\C=C/C=C)C(=O)C1 VXSIXFKKSNGRRO-MXOVTSAMSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- XLOPRKKSAJMMEW-UHFFFAOYSA-N chrysanthemic acid Chemical compound CC(C)=CC1C(C(O)=O)C1(C)C XLOPRKKSAJMMEW-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical class OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- 238000007269 dehydrobromination reaction Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- QQGCJLQAXNKFTR-UHFFFAOYSA-N ethyl 4,6-dibromo-6,7,7,7-tetrafluoro-3,3-dimethylheptanoate Chemical compound CCOC(=O)CC(C)(C)C(Br)CC(F)(Br)C(F)(F)F QQGCJLQAXNKFTR-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- HYJYGLGUBUDSLJ-UHFFFAOYSA-N pyrethrin Natural products CCC(=O)OC1CC(=C)C2CC3OC3(C)C2C2OC(=O)C(=C)C12 HYJYGLGUBUDSLJ-UHFFFAOYSA-N 0.000 description 1
- 229940070846 pyrethrins Drugs 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
-
- 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
- A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/40—Unsaturated compounds containing halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Indole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Den foreliggende oppfinnelse angår nye 3-substituerte 2,2-dimethyl-cyclopropancarboxylsyrer og lavere alkylestere derav som er anvendelige som utgangsmaterialer ved fremstilling av en ny klasse av pyrethroider, nærmere bestemt nye estere av 2,2-dimethyl-cyclopropancarboxylsyrer som i cyclopropylringens 3-stilling er substituert med en mettet eller umettet polyhalogenert kjede med 3 carbonatomer. The present invention relates to new 3-substituted 2,2-dimethyl-cyclopropane carboxylic acids and lower alkyl esters thereof which are useful as starting materials in the production of a new class of pyrethroids, more specifically new esters of 2,2-dimethyl-cyclopropane carboxylic acids which in the cyclopropyl ring's 3- position is substituted with a saturated or unsaturated polyhalogen chain with 3 carbon atoms.
Pyrethrinene (eller pyrethrum), dvs. estere av krysanthe-minsyre (2,2-dimethyl-2-isobutenyl-cyclopropancarboxylsyre) med et retronolon (2-alkenyl-3-methyl-cyclopent-2-en-4-olon), er insekticider av naturlig opprinnelse som utmerker seg ved hurtig og sterk insekticid virkning kombinert med lav toksisitet for pattedyr. The pyrethrins (or pyrethrum), i.e. esters of chrysanthemic acid (2,2-dimethyl-2-isobutenyl-cyclopropanecarboxylic acid) with a retronolone (2-alkenyl-3-methyl-cyclopent-2-en-4-olone), are insecticides of natural origin that are characterized by rapid and strong insecticidal action combined with low toxicity for mammals.
Imidlertid spaltes pyrethrum lett under atmosfæriske påvirkninger, og dette gjør pyrethrum uegnet for beskyttelse av jordbruksavlinger og begrenser det til innendørs bruk. Dessuten er dets fremstilling kostbar, delvis grunnet kompleksiteten av ekstraksjonsprosessene og delvis på grunn av nødvendigheten av å anvende forbindelsen sammen med egnede synergistiske forbindelser. However, pyrethrum decomposes easily under atmospheric influences, and this makes pyrethrum unsuitable for the protection of agricultural crops and limits it to indoor use. Moreover, its manufacture is expensive, partly due to the complexity of the extraction processes and partly due to the necessity of using the compound together with suitable synergistic compounds.
For å avhjelpe alle disse problemer er det fremstilt et stort antall forbindelser av' lignende struktur som pyrethrum (pyrethroider) med sikte på å bibeholde den insecticide virkning og den lave toksisitet overfor pattedyr og samtidig oppnå mole-kyler som er mer motstandsdyktige overfor atmosfæriske påvirkninger [se f.eks. "synthetic Pyrethroids" (M. Elliott Ed.) ACS Symposium Series nr. 42, Washington 1977]. In order to remedy all these problems, a large number of compounds of a similar structure to pyrethrum (pyrethroids) have been produced with the aim of maintaining the insecticidal effect and the low toxicity towards mammals and at the same time obtaining molecules which are more resistant to atmospheric influences [ see e.g. "synthetic Pyrethroids" (M. Elliott Ed.) ACS Symposium Series No. 42, Washington 1977].
Det har vært utført forskning rettet mot syntesen av Research aimed at the synthesis of
nye derivater av 2,2-dimethyl-cyclopropancarboxylsyre og analoge forbindelser og likeledes mot syntese av alkoholer analoge med cyclopentenoloner, og likeledes mot nye grupper med alkoholfunk-sjoner som lar seg forestre med derivatene av eller analoger av 2,2-dimethyl-cyclopropancarboxylsyre. Derivatene av 2,2-dimethyl-cyclopropancarboxylsyre som er substituert i 3-stiilingen, er tall-rike . new derivatives of 2,2-dimethyl-cyclopropanecarboxylic acid and analogous compounds and likewise towards the synthesis of alcohols analogous to cyclopentenolones, and likewise towards new groups with alcohol functions that can be esterified with the derivatives of or analogues of 2,2-dimethyl-cyclopropanecarboxylic acid. The derivatives of 2,2-dimethyl-cyclopropanecarboxylic acid which are substituted in the 3-stylation are numerous.
Blant de mest lovende med hensyn til stabilitet er de som i 3-stillingen har en 3,3-dihalogenvinylgruppe [J. Farkas et al., Chem. Listy 52, 688 (1958); M. Elliott et al., Nature (London) 246, 169 (1973); M. Elliott et al., J. Chem. Soc. , Perkin 1 , 1974 , 2470] . Among the most promising in terms of stability are those having in the 3-position a 3,3-dihalovinyl group [J. Farkas et al., Chem. Listy 52, 688 (1958); M. Elliott et al., Nature (London) 246, 169 (1973); M. Elliott et al., J. Chem. Soc. , Perkin 1 , 1974 , 2470] .
I den følgende tabell 1 er oppført noen av de syntetiske pyrethroider som har vist seg å ha interessante egenskaper. In the following table 1 are listed some of the synthetic pyrethroids which have been shown to have interesting properties.
I overensstemmelse med oppfinnelsen tilveiebringes det nye 2,2-dimethyl-cyclopropancarboxylsyrederivater som omfattes av den generelle formel (II): hvor R' er hydrogen eller alkyl med 1-4 carbonatomer, og A er In accordance with the invention, new 2,2-dimethyl-cyclopropanecarboxylic acid derivatives are provided which are covered by the general formula (II): where R' is hydrogen or alkyl with 1-4 carbon atoms, and A is
hvor X er hydrogen, fluor, klor eller brom, og Y er klor eller brom. where X is hydrogen, fluorine, chlorine or bromine, and Y is chlorine or bromine.
Forbindelsene av den generelle formel II er anvendelige som utgangsmaterialer ved fremstilling av de nye pyrethroider av den generelle formel I: The compounds of the general formula II are useful as starting materials in the preparation of the new pyrethroids of the general formula I:
i hvilken in which
A er CF3~C=C-, A is CF3~C=C-,
hvor where
X er hydrogen, fluor, klor eller brom, og X is hydrogen, fluorine, chlorine or bromine, and
Y er klor eller brom, Y is chlorine or bromine,
og R er and R is
hvor where
R<1> er hydrogen, CN eller C=CH, og R<1> is hydrogen, CN or C=CH, and
R <2>er 3-fenoxy, 3-benzyl, 4-allyl eller 4-propargyl, eller R er R <2> is 3-phenoxy, 3-benzyl, 4-allyl or 4-propargyl, or R is
hvor where
R<1> er hydrogen, CN eller C=CH, R<1> is hydrogen, CN or C=CH,
R er hydrogen eiler alkyl, R is hydrogen or alkyl,
R 4er benzyl, benzoyl, fenoxy, allyl eller propargyl, og R 4 is benzyl, benzoyl, phenoxy, allyl or propargyl, and
Y<*> er oxygen eller svovel, Y<*> is oxygen or sulphur,
idet gruppen CH er bundet til den heterocykliske ring in that the group CH is bound to the heterocyclic ring
R<1>R<1>
i 2- eller 3-stillingen, R 3 er bundet til den heterocykliske ring i 3- eller 2-stillingen, og R 4er bundet in the 2- or 3-position, R 3 is attached to the heterocyclic ring in the 3- or 2-position, and R 4 is attached
til den heterocykliske ring i 4- eller 5-stillingen, eller R er to the heterocyclic ring in the 4- or 5-position, or R is
hvor where
R~* og R^ er alkyl med 1-3 carbonatomer, eller R^ og R^ sammen danner en aromatisk eller alifatisk, R~* and R^ are alkyl with 1-3 carbon atoms, or R^ and R^ together form an aromatic or aliphatic,
mettet eller umettet, orthokondensert ring, eller R er saturated or unsaturated, ortho-fused ring, or R is
hvor where
R 7 og R 8, som kan være like eller forskjellige, betegner hydrogen, halogen eller CH,, og 9 J R er fenyl, vinyl eller fenoxy, R 7 and R 8 , which may be the same or different, represent hydrogen, halogen or CH,, and 9 J R is phenyl, vinyl or phenoxy,
eller R er or R is
hvor where
R 9 er fenyl, vinyl eller fenoxy.. R 9 is phenyl, vinyl or phenoxy..
Forbindelsene av den generelle formel (i)har høy aktivitet overfor insekter og likeledes midder. The compounds of the general formula (i) have high activity against insects and also mites.
Fremstillingen av forbindelsene med den generelle formel (I), samt anvendelsen av disse som aktive komponenter i insekti-cide midler, er beskrevet i stamsøknaden nr. 790621. The production of the compounds with the general formula (I), as well as their use as active components in insecticides, is described in parent application no. 790621.
En av fremgangsmåtene for fremstilling av derivatene av den generelle formel (II) tar utgangspunkt i polyfluorerte ethaner av formelen: One of the methods for producing the derivatives of the general formula (II) is based on polyfluorinated ethanes of the formula:
hvor X og Y har de betydninger som er angitt for den generelle formel (II), og følger de trinn som er angitt i skjema 1. Skjema 1 (R, X og Y har de ovenfor angitte betydninger) where X and Y have the meanings given for the general formula (II), and follow the steps given in form 1. Form 1 (R, X and Y have the meanings given above)
(II, X = H) (II, X = H)
1) Addering av en forbindelse CF3~C(X) Y2 til dobbeltbindingen i en 3 ,3-dimethyl-4-pentensyreester, i nærvær av fri-radikal aktivatorer i henhold til ligningen: 2) Ringslutning av det derved erholdte addukt i nærvær av en base: 3) Dehydrohalogenering ved ytterligere behandling med en base: 1) Addition of a compound CF3~C(X) Y2 to the double bond in a 3,3-dimethyl-4-pentenoic acid ester, in the presence of free-radical activators according to the equation: 2) Cyclization of the thus obtained adduct in the presence of a base: 3) Dehydrohalogenation by further treatment with a base:
Avhengig av betingelsene under hvilke de to siste reaksjoner utføres og avhengig av arten av halogenet Y kan trinn 3) forløpe etter hvert som trinn 2) forløper, eller det kan endog forløpe forut for dette, i henhold også til de følgende sekvenser: Depending on the conditions under which the last two reactions are carried out and depending on the nature of the halogen Y, step 3) can proceed as step 2) proceeds, or it can even proceed before this, according to the following sequences:
Når X i forbindelsene av den generelle formel IV betegner halogen, kan forbindelsene underkastes ytterligere en dehydro-halogeneringsreaksjon i henhold til ligningen: When X in the compounds of the general formula IV denotes halogen, the compounds can be further subjected to a dehydro-halogenation reaction according to the equation:
Også denne siste reaksjon kan, om ønsket, utføres sammen med trinnene 2 og 3, uten isolering av forbindelsene av den generelle formel IV. Also this last reaction can, if desired, be carried out together with steps 2 and 3, without isolating the compounds of the general formula IV.
De som utgangsmaterialer anvendte forbindelser av typen CF3-C(X)Y2 er alle kjente forbindelser, som lett kan fremstilles ut fra halogenerte polyfluorethaner, som er å få i handelen, ved hjelp av kjente omordningsreaksjoner. The compounds of the CF3-C(X)Y2 type used as starting materials are all known compounds, which can be easily prepared from commercially available halogenated polyfluoroethanes, by means of known rearrangement reactions.
Noen eksempler på forbindelser av typen CF-j-C(X)Y2 er: Some examples of compounds of the type CF-j-C(X)Y2 are:
CF3-CFBr2CF3-CFBr2
CF3-CBr3CF3-CBr3
CF3-CClBr2CF 3 -CClBr 2
CF3-CHClBr CF3-CHClBr
CF3-CC13CF3-CC13
Egnede aktivatorer for addisjonsreaksjon 1) er de organiske peroxyder, såsom tert-butylperoxyd, benzoylperoxyd eller diacetylperoxyd, azoderivater såsom azo-bis-isobutyronitril, komplekser inneholdende overgangsmetaller såsom f.eks. de som dannes mellom jern- eller kobbersalter og alifatiske aminer, eller også redox-overføringssystemer. Suitable activators for addition reaction 1) are the organic peroxides, such as tert-butyl peroxide, benzoyl peroxide or diacetyl peroxide, azo derivatives such as azo-bis-isobutyronitrile, complexes containing transition metals such as e.g. those formed between iron or copper salts and aliphatic amines, or also redox transfer systems.
Reaksjonen 1) utføres ved at man i nærvær av kataly-serende mengder av én av de ovennevnte fri-radikal-aktivatorer, omsetter polyhalogenethanet med en ester av 3,3-dimethyl-penten-syre, fortrinnsvis i et molforhold polyhalogenethan/ester høyere enn 1, ved temperaturer mellom 50° og 200° C. Reaction 1) is carried out by reacting the polyhalogenethane with an ester of 3,3-dimethylpentenoic acid, preferably in a polyhalogenethane/ester molar ratio higher than 1, at temperatures between 50° and 200° C.
Reaksjonen kan hensiktsmessig utføres i en autoklav, under autogent trykk, eller ved atmosfæretrykk, i inerte oppløs-ningsmidler og ved tilbakeløpstemperatur. The reaction can conveniently be carried out in an autoclave, under autogenous pressure, or at atmospheric pressure, in inert solvents and at reflux temperature.
Ringslutningsreaksjonen 2) finner sted under innvirkning av en sterk base såsom et alkalisk alkoholat eller natriumhydrid, i et polart oppløsningsmiddel og ved temperaturer mellom -20° og +50° C. The cyclization reaction 2) takes place under the influence of a strong base such as an alkaline alcoholate or sodium hydride, in a polar solvent and at temperatures between -20° and +50° C.
En forlenget behandling med den samme base eller under noe mere drastiske temperaturbétingelser kan forårsake ytterligere dehydrohalogenering etter ligning 3) og, når X er et halogen-atom, etter ligning 4). A prolonged treatment with the same base or under slightly more drastic temperature conditions can cause further dehydrohalogenation according to equation 3) and, when X is a halogen atom, according to equation 4).
Alternativt kan reaksjonen for elimineringen av syren HY utføres enten før eller etter ringslutningstrinnet, ved innvirkning av uorganiske baser eller av syreopptagende aminer. Alternatively, the reaction for the elimination of the acid HY can be carried out either before or after the ring-closing step, by the action of inorganic bases or of acid-absorbing amines.
Forbindelsene som fremstilles etter den ovenfor beskrevne fremgangsmåte, er vanligvis ethylestere eller methyl-estere, fra hvilke de tilsvarende syrer lett fåes ved vanlige hydrolysereaksjoner. The compounds produced according to the method described above are usually ethyl esters or methyl esters, from which the corresponding acids are easily obtained by ordinary hydrolysis reactions.
Når reaksjonene for eliminering av syrene HY .og HX utføres med uorganiske baser såsom natrium- eller kaliumhydroxyd, skjer samtidig hydrolysen av estergruppen, slik at forbindelsene, ved påfølgende surgjøring, fåes direkte i form av frie syrer. When the reactions for the elimination of the acids HY .and HX are carried out with inorganic bases such as sodium or potassium hydroxide, the hydrolysis of the ester group occurs at the same time, so that the compounds, upon subsequent acidification, are obtained directly in the form of free acids.
Forbindelser av formel II kan likeledes fremstilles etter en annen fremgangsmåte. Denne fremgangsmåte har som sitt første trinn addering av en forbindelse av formelen CF^-CXY2 til en ester av 2-alkoxycarbonyl-3,3-dimethyl-4-pentensyre av formelen: Compounds of formula II can likewise be prepared by another method. This method has as its first step the addition of a compound of the formula CF^-CXY2 to an ester of 2-Alkoxycarbonyl-3,3-dimethyl-4-pentenoic acid of the formula:
og følger to forskjellige retninger, avhengig av hvilken sub-stituent. A som ønskes i cyclopropylringen i 3-stilling. Utgangs-materialet (2-alkoxycarbonyl-3,3-dimethyl-4-pentensyreester) kan lett fremstilles ved omsetning av 3-klor-3-methyl-buten (1) med en malonsyreester (belgisk patentskrift nr. 851 524). and follows two different directions, depending on which sub-stituent. A which is desired in the cyclopropyl ring in the 3-position. The starting material (2-Alkoxycarbonyl-3,3-dimethyl-4-pentenoic acid ester) can be easily prepared by reacting 3-chloro-3-methyl-butene (1) with a malonic acid ester (Belgian Patent No. 851 524).
I det følgende skjema er oppført de trinn som i henhold til denne andre fremgangsmåte fører frem til forbindelsene av den generelle formel II. The following chart lists the steps which, according to this second method, lead to the compounds of the general formula II.
De forskjellige trinn som fremgår av skjema 2, skal The various steps that appear in form 2 shall
nu forklares i detalj. now explained in detail.
Reaksjon 1 (skjema 2) Reaction 1 (Scheme 2)
Reaksjon 1 utføres i nærvær av fri-radikal-aktivatorer såsom organiske peroxyder, f.eks. tert.-butylperoxyd, benzoylperoxyd eller diacetylperoxyd; azo-derivater såsom azo-bis-isobutyronitril, komplekser inneholdendé salter av overgangsmetaller så-såsom f.eks. de som dannes mellom jern- eller kobbersalter og alifatiske aminer, eller redox-overføringssystemer. Reaction 1 is carried out in the presence of free-radical activators such as organic peroxides, e.g. tert-butyl peroxide, benzoyl peroxide or diacetyl peroxide; azo derivatives such as azo-bis-isobutyronitrile, complexes containing salts of transition metals such as e.g. those formed between iron or copper salts and aliphatic amines, or redox transfer systems.
Reaksjon (1) utføres ved at man i nærvær av katalyse-rende mengder av én av de ovennevnte fri-radikal-aktivatorer, omsetter et polyhalogenethan av formelen CF3~CXY2 med en ester av 2-alkoxycarbonyl-3,3-dimethyl-4-pentensyre, fortrinnsvis i et molforhold polyhalogenethan/ester som er større enn 1, ved temperaturer mellom 50 og 200° C. Reaksjonen kan hensiktsmessig utføres i en autoklav, under et autogent trykk eller under atmosfæretrykk, i inerte oppløsningsmidler ved tilbakeløpstemperatur. Reaction (1) is carried out by reacting a polyhaloethane of the formula CF3~CXY2 with an ester of 2-Alkoxycarbonyl-3,3-dimethyl-4- pentenoic acid, preferably in a polyhalogenethane/ester molar ratio greater than 1, at temperatures between 50 and 200° C. The reaction can conveniently be carried out in an autoclave, under an autogenous pressure or under atmospheric pressure, in inert solvents at reflux temperature.
Noen eksempler på forbindelser av typen CF3~C(X)Y2 er: CF3-CFBr2Some examples of compounds of the type CF3~C(X)Y2 are: CF3-CFBr2
CF3-CBr3CF3-CBr3
CF3-CClBr2CF 3 -CClBr 2
CF3CHClBr CF3CHClBr
CF3-CC13CF3-CC13
Reaksjon 2 (skjema 2) Reaction 2 (Scheme 2)
Denne reaksjon utføres ved at adduktet erholdt ved reaksjon" 1 (B) behandles med en ekvivalent mengde av en alkalisk base (NaHC03, Na2C03, K2C03, KOH, NaOH, C2H5ONa) i et organisk oppløsningsmiddel. This reaction is carried out by treating the adduct obtained in reaction "1 (B) with an equivalent amount of an alkaline base (NaHC03, Na2C03, K2C03, KOH, NaOH, C2H5ONa) in an organic solvent.
Derved erholdes diesteren av 1,1-cyclopropandicarboxyl-syre, som er angitt ved bokstaven (C) i skjema 2. Idet man star-ter med forbindelse (C) kan man gå flere veier for å modifisere den polyhalogenerte kjede i cyclopropylringens 3-stilling og for å utføre decarboxyleringen. Thereby the diester of 1,1-cyclopropanedicarboxylic acid is obtained, which is indicated by the letter (C) in scheme 2. Starting with compound (C), one can take several routes to modify the polyhalogenated chain in the 3-position of the cyclopropyl ring and to carry out the decarboxylation.
Reaksjon 3 (skjema 2) Reaction 3 (Scheme 2)
Det i trinn 2 erholdte cyclopropanderivat dehydrohalogeneres ved behandling med en ekvivalent mengde av en alkalisk base, idet sistnevnte fortrinnsvis er et natriumalkoholat. Even-tuelt kan den"samme type mellomprodukt erholdes direkte ut fra adduktet beskrevet i trinn 1, ved behandling med to ekvivalenter av en alkalisk base. Derved fåes cyclopropandicarboxylatet angitt ved bokstaven (D). The cyclopropane derivative obtained in step 2 is dehydrohalogenated by treatment with an equivalent amount of an alkaline base, the latter preferably being a sodium alcoholate. Optionally, the same type of intermediate product can be obtained directly from the adduct described in step 1, by treatment with two equivalents of an alkaline base. This gives the cyclopropane dicarboxylate indicated by the letter (D).
Reaksjon 4 (skjema 2) Reaction 4 (Scheme 2)
Forbindelse D dehydrohalogeneres ytterligere (når X er klor eller brom) ved behandling med et overskudd av en base, fortrinnsvis et alkalisk alkoholat, eller med NaNI^ i et organisk oppløsningsmiddel. Compound D is further dehydrohalogenated (when X is chlorine or bromine) by treatment with an excess of a base, preferably an alkaline alcoholate, or with NaN1^ in an organic solvent.
Derved fåes mellomproduktet (E). Thereby the intermediate product (E) is obtained.
Reaksjon 5 (skjema 2) Reaction 5 (Scheme 2)
Cyclopropandicarboxylat (C) underkastes hydrogenolyse ved innvirkning av sinkpulver i saltsyre, i eddiksyre eller i methyl- eller ethylalkohol, hvorved mellomproduktet (F) dannes. Cyclopropane dicarboxylate (C) is subjected to hydrogenolysis by the action of zinc powder in hydrochloric acid, in acetic acid or in methyl or ethyl alcohol, whereby the intermediate product (F) is formed.
Denne reaksjon utføres når X er klor eller brom, og fører til innføring av et hydrogenatom i stedet for halogenatomet This reaction is carried out when X is chlorine or bromine, and leads to the introduction of a hydrogen atom instead of the halogen atom
(X = H) . (X = H).
Reaksjon 6 (skjema 2) Reaction 6 (Scheme 2)
Mellomproduktet (F) underkastes dehydrohalogenering under de samme reaksjonsbetingelser sammen med reaksjon 3, hvorved man får mellomproduktet (G), som også kan fåes ved kataly-tisk hydrogenering (reaksjon 7, skjema 2) av trippelbindingen i kjeden i 3-stilling av mellomproduktets (E) cyclopropylring. Katalysatorsystemet som anvendes ved reaksjon 7, kan velges blant de som det er vanlig å anvende for selektive reduksjoner av trippelbindinger til dobbeltbindinger, såsom f.eks.: The intermediate product (F) is subjected to dehydrohalogenation under the same reaction conditions together with reaction 3, whereby the intermediate product (G) is obtained, which can also be obtained by catalytic hydrogenation (reaction 7, scheme 2) of the triple bond in the chain in the 3-position of the intermediate's ( E) cyclopropyl ring. The catalyst system used in reaction 7 can be chosen from among those that are commonly used for selective reductions of triple bonds to double bonds, such as, for example:
hydrogen på en forgiftet palladiumkatalysator, hydrogen on a poisoned palladium catalyst,
Na/NH.j væske, Na/NH.j liquid,
hydroborering med påfølgende hydrolyse med alifatiske syrer (Tetrahedron 1977, 33, s. 1845). hydroboration with subsequent hydrolysis with aliphatic acids (Tetrahedron 1977, 33, p. 1845).
Ved hjelp av de hittil beskrevne reaksjoner fåes cyclo-propandicarboxylater (C, D. E, F, G) som i 3-stillingen allerede bærer de polyhalogenerte kjeder som svarer til de forskjellige betydninger av substituenten A i den generelle formel (II). By means of the reactions described so far, cyclo-propane dicarboxylates (C, D, E, F, G) are obtained which in the 3-position already carry the polyhalogenated chains which correspond to the different meanings of the substituent A in the general formula (II).
Ut fra disse fås ved decarboxylering (reaksjon 8) forbindelsene From these, the compounds are obtained by decarboxylation (reaction 8).
av den generelle formeler (IV) og (V). of the general formulas (IV) and (V).
Reaksjon 8 (skjema 2) Reaction 8 (Scheme 2)
Mellomproduktene (C, D, E, F, G) underkastes decarboxylering under den ene eller den annen av de følgende betingelser: 8a) Total eller partiell hydrolyse med syrer eller alkali i alkohol med påfølgende oppvarming av de tilsvarende syrer i nøytrale eller basiske organiske oppløsningsmidler, ved temperaturer mellom 100° og 2 50° C. 8b.) Hydrolyse som under 8a) , med påfølgende oppvarming i kinolin i nærvær av kobber, ved temperaturer mellom 100° og 250° C. 8c) Oppvarming i aprotiske polare oppløsningsmidler såsom dimethylsulfoxyd i nærvær av alkalihalogenider eller -cyanider, og i nærvær av støkiometriske mengder vann (2 ekvivalenter). The intermediate products (C, D, E, F, G) are subjected to decarboxylation under one or the other of the following conditions: 8a) Total or partial hydrolysis with acids or alkali in alcohol with subsequent heating of the corresponding acids in neutral or basic organic solvents, at temperatures between 100° and 250° C. 8b.) Hydrolysis as under 8a), with subsequent heating in quinoline in the presence of copper, at temperatures between 100° and 250° C. 8c) Heating in aprotic polar solvents such as dimethylsulfoxide in the presence of alkali halides or cyanides, and in the presence of stoichiometric amounts of water (2 equivalents).
Man fikk således forbindelser av den generelle formel(II) i form av carboxylsyrer (r'= H), fra hvilke det er mulig å fremstille, om så måtte ønskes, de tilsvarende estere ved hjelp av konvensjonelle forestringsreaksjoner, eller i form av estere fra hvilke det er mulig, om så måtte ønskes, å fremstille de tilsvarende syrer ved hjelp av konvensjonelle hydrolysereaksjoner. Compounds of the general formula (II) were thus obtained in the form of carboxylic acids (r'= H), from which it is possible to prepare, if desired, the corresponding esters by means of conventional esterification reactions, or in the form of esters from which it is possible, if desired, to prepare the corresponding acids by means of conventional hydrolysis reactions.
Den følgende tabell 3 sammenfatter de reaksjoner som i henhold til fremgangsmåten ifølge skjema 2 fører til de forskjellige forbindelser som faller inn under den generelle formel II. The following table 3 summarizes the reactions which according to the method according to scheme 2 lead to the various compounds which fall under the general formula II.
Etter de ovenfor beskrevne fremgangsmåter ble de forbindelser av den generelle formel II som er oppført i den følgen-de tabell 3, fremstilt. According to the methods described above, the compounds of the general formula II listed in the following Table 3 were prepared.
Tabell 3 Table 3
Forbindelser av den generelle formel II Compounds of the general formula II
Anmerkninger til tabell 3 Notes to Table 3
(a) MS = Massespektroskopiske data; kun de viktigste ioner er (a) MS = Mass spectroscopic data; only the most important ions are
oppført. listed.
(b) R.I. = Brytningsindeks. (b) R.I. = Refractive index.
(c) NMR = <1>H Data for det kjernemagnetiske resonansspektrum, (c) NMR = <1>H Data for the nuclear magnetic resonance spectrum,
NMR-spektrene ble tatt opp under anvendelse av CDCl-^ som oppløsningsmiddel og TMS som intern standard, The NMR spectra were recorded using CDCl-^ as solvent and TMS as internal standard,
s = singlett, d = dublett, t = triplett, Q = kvartett, s = singlet, d = doublet, t = triplet, Q = quartet,
m = multiplett; J = koblingskonstant. m = multiplet; J = coupling constant.
(d) IR = Data for det infrarøde spektrum; kun de mest betydnings-fulle bånd er tatt med. (d) IR = Data for the infrared spectrum; only the most significant ties are included.
19 19
(e) F NMR-spektere ble tatt opp under anvendelse av CDCl^ som oppløsningsmiddel og CFCI2 som intern standard; d = (e) F NMR spectra were recorded using CDCl 2 as solvent and CFCl 2 as internal standard; d =
dublett. duplicate.
(f) smeltepunktet er ikke blitt korrigert. (f) the melting point has not been corrected.
Pyrethroidene av den generelle formel I kan lett fremstilles ut fra cyclopropancarboxylsyrene og -estrene av den generelle formel II ved hjelp av fremgangsmåter som er helt vanlige i den organiske kjemi. Eksempelvis er det mulig å overføre syrene og estrene av formel II til de tilsvarende acylhalogenider, som ved omsetning med alkoholer av formel R-OH (hvor R har den i formel I angitte betydning) gir forbindelsene av formel I. The pyrethroids of the general formula I can be easily prepared from the cyclopropane carboxylic acids and esters of the general formula II using methods that are quite common in organic chemistry. For example, it is possible to transfer the acids and esters of formula II to the corresponding acyl halides, which upon reaction with alcohols of formula R-OH (where R has the meaning given in formula I) give the compounds of formula I.
Den særegne struktur av syrene og estrene av formel II er årsak til diverse geometriske og konfigurasjonene isomerer hvis r eksistens skyldes de følgende faktorer: - den asymmetriske natur av carbonatomene 1 og 3 i cyclopropylringen (enantiomere); - den relative romlige innretning av. gruppen COOR' og av substituenten A i forhold til cyclopropylringens plan (cis eller The peculiar structure of the acids and esters of formula II is the cause of various geometrical and configurational isomers whose r existence is due to the following factors: - the asymmetric nature of carbon atoms 1 and 3 in the cyclopropyl ring (enantiomers); - the relative spatial arrangement of. the group COOR' and of the substituent A in relation to the plane of the cyclopropyl ring (cis or
trans), trans),
- cis- eller trans-isomere av substituentene som er tilstede ved dobbeltbindingen i de tilfeller hvor A = CF^-C=CH-. - cis- or trans-isomers of the substituents present at the double bond in the cases where A = CF^-C=CH-.
X X
Separeringen av de forskjellige isomerblandinger i de ulike stereoisomere og deres enantiomere kan oppnås ved hjelp av kjente kjemiske metoder, såsom f.eks. henholdsvis kromatografi-metoder og utfeining av salter med optisk aktive baser. The separation of the different isomer mixtures into the different stereoisomers and their enantiomers can be achieved by means of known chemical methods, such as e.g. respectively, chromatography methods and purification of salts with optically active bases.
Alle steriske og/eller konfigurasjonene isomerer som kan fåes fra blandingen av forbindelser av formel II fremstilt i henhold til den beskrevne prosess, kan anvendes, og likeledes blandingene i seg selv og fraksjoner av blandingene erholdt ved partiell eller fullstendig separasjon av stereoisomerer. All steric and/or configurational isomers obtainable from the mixture of compounds of formula II prepared according to the described process can be used, as well as the mixtures themselves and fractions of the mixtures obtained by partial or complete separation of stereoisomers.
De følgende eksempler gir en mer detaljert beskrivelse The following examples provide a more detailed description
av oppfinnelsen. Eksemplene 1, 3, 5, 11, 12 og 14 vedrører fremstilling av utgangsmaterialer for fremstillingen av forbindelser med formel (II). of the invention. Examples 1, 3, 5, 11, 12 and 14 relate to the preparation of starting materials for the preparation of compounds of formula (II).
Eksempel 1 Example 1
Fremstilling av mellomproduktet ethylester av 3, 3- dimethyl- 4, 6-dibrom- 6, 7, 7, 7- tetrafluor- heptansyre Preparation of the intermediate ethyl ester of 3,3-dimethyl-4,6-dibromo-6,7,7,7-tetrafluoroheptanoic acid
I en autoklav med kapasitet på 200 ml ble de følgende reagenser innført under nitrogenatomsfære: 17 g ethylester av 3,3-dimethyl-4-pentensyre (0,005 mol), 55 g 1,1,1,2-tetrafluordi-bromethan (0,21 mol), 0,5 ml tert.-butylperoxyd. In an autoclave with a capacity of 200 ml, the following reagents were introduced under a nitrogen atmosphere: 17 g of ethyl ester of 3,3-dimethyl-4-pentenoic acid (0.005 mol), 55 g of 1,1,1,2-tetrafluorodibromoethane (0, 21 mol), 0.5 ml tert-butyl peroxide.
Autoklaven ble deretter dykket ned i et oljebad og rystet mekanisk i 5 timer ved 120° C. Etter avkjøling ble innholdet fortynnet med 100 ml CH2C12. Oppløsningen ble deretter vasket med vann (3 x 50 ml) inneholdende små mengder FeSO^ og tørket med vannfritt CaCl2, hvoretter oppløsningsmidlet ble avdestillert under vakuum. Det ble erholdt 43,3 g råprodukt som ble destillert under vakuum, og fraksjonen som kokte ved en tempeatur mellom 97 og 99° C ved 0,25 mmHg ble oppsamlet. Det ble erholdt.39 g ethyl-3,3-dimethyl-4,6-dibrom-6,7,7,7-tetrafluorheptanoat. The autoclave was then immersed in an oil bath and mechanically shaken for 5 hours at 120° C. After cooling, the contents were diluted with 100 ml of CH 2 Cl 2 . The solution was then washed with water (3 x 50 ml) containing small amounts of FeSO 4 and dried with anhydrous CaCl 2 , after which the solvent was distilled off under vacuum. 43.3 g of crude product was obtained which was distilled under vacuum, and the fraction boiling at a temperature between 97 and 99°C at 0.25 mmHg was collected. 39 g of ethyl 3,3-dimethyl-4,6-dibromo-6,7,7,7-tetrafluoroheptanoate were obtained.
Elementæranalyse: Elemental analysis:
Brom: teoretisk. 38,41 %; Funnet 37,83 % Bromine: theoretical. 38.41%; Found 37.83%
Eksempel 2 Example 2
Fremstilling av ethylesteren av 2 , 2- dimethyl^ 3-( 3~ f luor- ft- tri-fluormethyl- vinyl)- cyclopropancarboxylsyre og den frie syre Preparation of the ethyl ester of 2,2-dimethyl^3-(3-fluoro-ft-tri-fluoromethyl-vinyl)-cyclopropanecarboxylic acid and the free acid
Til en oppløsning av 25 g (0,06 mol) ethyl-3,3-dimethyl-4,6-dibrom-6,7,7,7-tetrafluorhepanoat.erholdt som beskrevet i eksempel 1, i 50 ml ethanol, ble det ved en temperatur mellom 23° og 32° C og under omrøring tilsatt 0,132 mol natriumethylat opp-løst i 150 ml ethanol. To a solution of 25 g (0.06 mol) of ethyl 3,3-dimethyl-4,6-dibromo-6,7,7,7-tetrafluorohepanoate, obtained as described in example 1, in 50 ml of ethanol, at a temperature between 23° and 32° C and with stirring added 0.132 mol of sodium ethylate dissolved in 150 ml of ethanol.
Etter fullført tilsetning ble den erholdte oppløsning holdt ved romtemperatur i 3 timer. Det ble deretter tatt ut 50 ml av oppløsningen, og disse 50 ml ble konsentrert til et redusert volum. Den erholdte oppløsning ble deretter helt over i vann og is. Oppløsningen ble så ekstrahert med 50 ml CH2C12, og den organiske fase ble vasket med vann inntil det ble oppnådd en nøy-tral pH-verdi. Deretter ble oppløsningen tørret med vannfritt CaCl2 og oppløsningsmidlet fjernet under vakuum. After completion of the addition, the resulting solution was kept at room temperature for 3 hours. 50 ml of the solution was then taken out, and these 50 ml were concentrated to a reduced volume. The resulting solution was then poured into water and ice. The solution was then extracted with 50 ml of CH 2 Cl 2 , and the organic phase was washed with water until a neutral pH value was obtained. Then the solution was dried with anhydrous CaCl 2 and the solvent was removed under vacuum.
Det ble på denne måte erholdt 3,6 g av et urent reak-sjonsprodukt som, analysert ved gasskromatografi kombinert med massespektrometri, viste seg å bestå overveiende av ethylesteren av 2,2-dimethyl-3-(3~fluor-3-trifluormethyl-vinyl)-cyclopropancarboxylsyre (forbindelse a, tabell 3) som kunne isoleres fra råproduktet ved søylekromatografi, og av ethylesteren av 2,2-dimethyl-3-(3-brom~3, Y , Y,Y~tetrafluorpropyl)-cyclopropancarboxylsyre (ca. 20 % av råproduktet) (forbindelse b i tabell 3). In this way, 3.6 g of an impure reaction product were obtained which, analyzed by gas chromatography combined with mass spectrometry, proved to consist predominantly of the ethyl ester of 2,2-dimethyl-3-(3~fluoro-3-trifluoromethyl- vinyl)-cyclopropanecarboxylic acid (compound a, Table 3) which could be isolated from the crude product by column chromatography, and of the ethyl ester of 2,2-dimethyl-3-(3-bromo~3, Y , Y,Y~tetrafluoropropyl)-cyclopropanecarboxylic acid (ca .20% of the crude product) (compound b in Table 3).
Den gjenværende del av ethanoloppløsningen, fra hvilken det var blitt tatt 50 ml, ble behandlet med 6 g 85 %-ig KOH i 30 ml ethanol. The remaining part of the ethanol solution, from which 50 ml had been taken, was treated with 6 g of 85% KOH in 30 ml of ethanol.
Reaksjonsblandingen ble deretter oppvarmet i 2 timer ved tilbakeløpstemperaturen i den hensikt å foreta hydrolyse av esteren samt for å fullføre dehydrobromeringen av 3_brom-3, Y , Y , Y _ tetrafluorpropylgruppen. Reaksjonsblandingen ble deretter konsentrert til et redusert volum og deretter helt over i vann og is. Blandingen ble surgjort med fortynnet H-jSO^ og deretter ekstrahert med CH2C12 (3 x 50 ml), hvoretter den organiske fase ble vasket med en vandig oppløsning av NaCl (2 x 100 ml) og tørket over vannfritt CaCl2. The reaction mixture was then heated for 2 hours at the reflux temperature in order to hydrolyze the ester and to complete the dehydrobromination of the 3_bromo-3, Y , Y , Y _ tetrafluoropropyl group. The reaction mixture was then concentrated to a reduced volume and then poured into water and ice. The mixture was acidified with dilute H 2 SO 4 and then extracted with CH 2 Cl 2 (3 x 50 mL), after which the organic phase was washed with an aqueous solution of NaCl (2 x 100 mL) and dried over anhydrous CaCl 2 .
Oppløsningsmidlet ble fjernet under vakuum, hvorved det ble erholdt 8 g 2,2-dimethyl-3-(3~fluor-3-trifluormethyl-vinyl )-cyclopropancarboxylsyre) i form av en viskøs, strågul olje (forbindelse c i tabell 3). The solvent was removed under vacuum, whereby 8 g of 2,2-dimethyl-3-(3~fluoro-3-trifluoromethyl-vinyl)-cyclopropanecarboxylic acid) were obtained in the form of a viscous, straw-yellow oil (compound c in Table 3).
Eksempel 3 Example 3
F remstilling av mellomproduktet 3, 3- dimethyl- 4, 6, 6- tribrom- 7, 7, 7-trifluor- heptansyre- ethylester Preparation of the intermediate 3,3-dimethyl-4,6,6-tribromo-7,7,7-trifluoro-heptanoic acid ethyl ester
I en autoklav med kapasitet 200 ml ble de følgende In an autoclave with a capacity of 200 ml, the following were obtained
reaktanter innført under nitrogenatmosfære: reactants introduced under nitrogen atmosphere:
13 g ethylester av 3,3-dimethyl-4-pentensyre (0,083 mol), 13 g ethyl ester of 3,3-dimethyl-4-pentenoic acid (0.083 mol),
53 g 1,1,1-trifluor-2,2,2-tribromethan (0,166 mol), 53 g of 1,1,1-trifluoro-2,2,2-tribromoethane (0.166 mol),
0,5 ml tert.-butylperoxyd. 0.5 ml tert-butyl peroxide.
Autoklaven ble deretter anbragt i et oljebad og mekanisk rystet i 5 timer ved 120° C og deretter i 1 time ved 130° C. Etter nedkjøling ble innholdet fortynnet med 100 ml methylenklorid. Oppløsningen ble deretter vasket med vann (3 x 50 ml) inneholdende små mengder ferrosulfat og deretter tørret over vannfritt CnC.l2. KLter f jerning av oppløsningsmidlet vad fordampning ble råproduktet destillert under vakuum. Fraksjonen med kokepunkt 117 - 118° C ved 0,15 mmHg ble oppsamlet. Den besto av 31,3 g 3,3-dimethyl-4,6,6-tribrom-7,7,7-trifluor-heptansyre-ethylester. Elementæranalyse: The autoclave was then placed in an oil bath and mechanically shaken for 5 hours at 120° C. and then for 1 hour at 130° C. After cooling, the contents were diluted with 100 ml of methylene chloride. The solution was then washed with water (3 x 50 mL) containing small amounts of ferrous sulfate and then dried over anhydrous CnCl 2 . After removal of the solvent by evaporation, the crude product was distilled under vacuum. The fraction with boiling point 117 - 118° C at 0.15 mmHg was collected. It consisted of 31.3 g of 3,3-dimethyl-4,6,6-tribromo-7,7,7-trifluoroheptanoic acid ethyl ester. Elemental analysis:
Brom: teoretisk = 50,26 %; funnet = 48,57 %. Bromine: theoretical = 50.26%; found = 48.57%.
Eksempel 4 Example 4
Til en oppløsning av 4,7 g 3,3-dimethyl-4,6,6-tribrom-7,7,7-trifluor-heptansyre-ethylester (fremstilt som beskrevet i eksempel 3) i 10 ml ethanol ble det under omrøring og under opp-rettholdelse av temperaturen mellom 19° og 23° C tilsatt en opp-løsning av 0,022 mol natriumethylat i 60 ml ethanol. Den erholdte oppløsning ble holdt ved romtemperatur i 3 timer, nemlig inntil det ved kontroll utført gasskromatografering viste seg at den som utgangsmateriale anvendte ester var helt forsvunnet. To a solution of 4.7 g of 3,3-dimethyl-4,6,6-tribromo-7,7,7-trifluoroheptanoic acid ethyl ester (prepared as described in example 3) in 10 ml of ethanol was added while stirring and while maintaining the temperature between 19° and 23° C, a solution of 0.022 mol of sodium ethylate in 60 ml of ethanol is added. The resulting solution was kept at room temperature for 3 hours, namely until gas chromatography carried out as a control showed that the ester used as starting material had completely disappeared.
Oppløsningen ble deretter konsentrert til et redusert volum, helt over i vann og is og deretter ekstrahert med CH2C12The solution was then concentrated to a reduced volume, poured into water and ice and then extracted with CH 2 Cl 2
(3 x 50 ml). Den organiske oppløsning ble så vasket med vann inntil en nøytral pH-verdi var nådd, og deretter tørket over vannfritt CaCl2. (3 x 50 ml). The organic solution was then washed with water until a neutral pH was reached, and then dried over anhydrous CaCl 2 .
Oppløsningsmidlet ble deretter fjernet under vakuum, hvorved det ble erholdt 2,6 g råprodukt, som ved søylekromatogra-fering ble separert i fire fraksjoner. Tre av disse fraksjoner, som ble analysert ved gasskromatografering og identifisert ved gasskromatografering kombinert med massespektrometri, viste seg å være som følger: Fraksjon I (0,3 g) = ethylester av 2,2-dimethyl-3-(3-brom-3-tri- fluormethyl-vinyl)-cyclopropancarboxylsyre (forbindelse d i tabell 3), The solvent was then removed under vacuum, whereby 2.6 g of crude product was obtained, which was separated into four fractions by column chromatography. Three of these fractions, which were analyzed by gas chromatography and identified by gas chromatography combined with mass spectrometry, were found to be as follows: Fraction I (0.3 g) = ethyl ester of 2,2-dimethyl-3-(3-bromo-3 -tri- fluoromethyl-vinyl)-cyclopropanecarboxylic acid (compound d in Table 3),
Fraksjon II (0,5 g)= blanding bestående av ca. 55 % av forbindelse d, ca. 20 % av forbindelsen som utgjorde fraksjon III (forbindelse f) og ca. 25 % av ethylesteren av 2,2-dimethyl-3-(3,3-dibrom-Y i y , Y-trifluor-propyl)-cyclopropancarboxylsyre (forbindelse e i tabell 3), Fraction II (0.5 g) = mixture consisting of approx. 55% of compound d, approx. 20% of the compound that made up fraction III (compound f) and approx. 25% of the ethyl ester of 2,2-dimethyl-3-(3,3-dibromo-Y i y , Y-trifluoro-propyl)-cyclopropanecarboxylic acid (compound e in Table 3),
Fraksjon III (0,6 g) = ethylesteren av 2,2-dimethyl-3-(3-trifluor-methyl-ethynyl)-cyclopropancarboxylsyre (forbindelse f i tabell 3). Fraction III (0.6 g) = the ethyl ester of 2,2-dimethyl-3-(3-trifluoro-methyl-ethynyl)-cyclopropanecarboxylic acid (compound f in Table 3).
(trans-isomer). (trans isomer).
Eksempel 5 Example 5
Fremstilling av mellomproduktet 3, 3- dimethyl- 4, 6, 6- triklor- 7, 7, 7-trifluor- heptansyre- ethylester Preparation of the intermediate 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluoro-heptanoic acid ethyl ester
I en 100 ml's kolbe ble de følgende reaktanter innført In a 100 ml flask, the following reactants were introduced
i nitrogenatmosfære: in a nitrogen atmosphere:
7,8 g ethylester av 3,3-dimethyl-4-pentensyre (0,05 mol), 7.8 g of ethyl ester of 3,3-dimethyl-4-pentenoic acid (0.05 mol),
18,75 g 1,1,1-trifluor-triklorethan (0,1 mol), 18.75 g 1,1,1-trifluorotrichloroethane (0.1 mol),
0,25 g kuproklorid, 0.25 g cupric chloride,
3,5 ml ethanolamin, 3.5 ml ethanolamine,
50 ml tert.-butylalkohol. 50 ml tert.-butyl alcohol.
Reaksjonsblandingen ble deretter oppvarmet ved tilbake-løpstemperatur i 10 timer. J.tter nedkjøling ble tert.-butylalkoho-len fjernet ved fordampning. The reaction mixture was then heated at reflux temperature for 10 hours. After cooling, the tert-butyl alcohol was removed by evaporation.
Residuet ble etter fortynning med 50 ml diethylether behandlet med fortynnet HC1 inntil en syr pH var nådd. Etherfasen ble deretter vasket med vann, nøytralisert med NaHCO^ og tørret over Na2SO^, og oppløsningsmidlet ble avdrevet, hvorved det ble erholdt 17,2 g av en olje som ved destillasjon under vakuum ga 13,2 g av en fraksjon med kokepunktsområde 105 - 110° C ved 0,6 mmHg, og som besto av 3,3-dimethyl-4,6,6-triklor-7,7,7-trifluor-heptansyre-ethylester (gasskromatografisk titer = 93 %). After dilution with 50 ml of diethyl ether, the residue was treated with dilute HCl until an acidic pH was reached. The ether phase was then washed with water, neutralized with NaHCO^ and dried over Na2SO^, and the solvent was evaporated, whereby 17.2 g of an oil was obtained which, on distillation under vacuum, gave 13.2 g of a fraction with a boiling point range of 105 - 110° C at 0.6 mmHg, and which consisted of 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluoroheptanoic acid ethyl ester (gas chromatographic titer = 93%).
Elementæranalyse: klor Elemental analysis: chlorine
Teoretisk = 30,96 %, funnet = 30,36 % Theoretical = 30.96%, found = 30.36%
IR-spekteret og NflR-spekteret for dette produkt stemte med den angitte struktur. The IR spectrum and the NflR spectrum of this product were consistent with the given structure.
Eksempel 6 Example 6
Fremstilling av ethylesteren av (+)- cis , trans- 2 , 2- dimethyl- 3-(( 3-klor- p- trifluormethyl- vinyl)- cyclopropancarrboxylsyre ( blanding av isomere) ( forbindelse g) Preparation of the ethyl ester of (+)-cis, trans-2, 2-dimethyl-3-((3-chloro-p-trifluoromethyl-vinyl)-cyclopropanecarboxylic acid (mixture of isomers) (compound g)
Til en oppløsning av 0,06 mol natriumethylat i 30 ml absolutt ethanol ble det ved en temperatur på -20° C tilsatt en oppløsning 10 ml ethanol av 11 g (0,3 mol) av mellomproduktet fremstilt i henhold til eksempel 5. Reaksjonsblandingen ble holdt under omrøring i 1 time ved 0° C. Etter henstand natten over ble omrøringen igjen opptatt i 2 timer ved 50 - 60° C. To a solution of 0.06 mol of sodium ethylate in 30 ml of absolute ethanol was added at a temperature of -20° C a solution of 10 ml of ethanol of 11 g (0.3 mol) of the intermediate product prepared according to example 5. The reaction mixture was kept under stirring for 1 hour at 0° C. After resting overnight, the stirring was resumed for 2 hours at 50 - 60° C.
Etter nedkjøling og frafiltrering av 3,8 g utfelt natriumklorid ble oppløsningen helt over i vann og is og ble ekstrahert med 3 x 30 ml diethylether. Den organiske ekstrakt ble vasket med vann og tørret over vannfritt Na2S0^. Oppløsningsmid-let ble avdrevet, hvorved det ble erholdt 8,1 g av en olje som på grunnlag av gasskromatograferinganalyse med påfølgende identi-fisering ved masse-gasskromatografering viste seg å bestå overveiende av isomerene av forbindelse g (ca. 83 %) og av en mindre mengde (ca. 12 %) av forbindelse f. IR-spekteret for denne blanding viste absorpsjonskarakteristika for dobbeltbindingen (C=C After cooling and filtering off 3.8 g of precipitated sodium chloride, the solution was poured into water and ice and extracted with 3 x 30 ml of diethyl ether. The organic extract was washed with water and dried over anhydrous Na 2 SO 4 . The solvent was driven off, whereby 8.1 g of an oil was obtained which, on the basis of gas chromatography analysis with subsequent identification by mass gas chromatography, proved to consist predominantly of the isomers of compound g (approx. 83%) and of a smaller amount (about 12%) of compound f. The IR spectrum of this mixture showed absorption characteristics of the double bond (C=C
(v = 1650 cm "*"), for trippelbindingen C=C (v = 2250 cm<->"<*>") og for C=0-estergruppen (v = 1720 cm ^~). (v = 1650 cm "*"), for the triple bond C=C (v = 2250 cm<->"<*>") and for the C=0 ester group (v = 1720 cm ^~).
Eksempel 7 Example 7
F remstilling av ethylesteren av (+)- cis, trans- 2, 2- dimethyl- 3-(&-trifluormethyl- ethynyl)- cyclopropancarboxylsyre ( blanding av isomere ) Preparation of the ethyl ester of (+)-cis, trans-2, 2- dimethyl- 3-(&-trifluoromethyl- ethynyl)- cyclopropanecarboxylic acid (mixture of isomers)
I en godt tørret rundkolbe av kapasitet 250 ml, som var utstyrt med en tilbakeløpskondensator ble det Innført 8 g av en 25 %-ig konsentrasjon av natriumamid i Degussa-olje under 50 ml vannfritt benzen hvoretter de følgende reaktanter ble tilsatt ved 0° C og under nitrogenatmosfære: 13,5 g ethylester av 2 , 2-dimethyl-3-((3-klor-(3-trif luormethyl-vinyl )-cyclopropancarboxylsyre (blanding av isomere) In a well-dried round-bottomed flask of capacity 250 ml, which was equipped with a reflux condenser, 8 g of a 25% concentration of sodium amide in Degussa oil were introduced under 50 ml of anhydrous benzene, after which the following reactants were added at 0° C and under a nitrogen atmosphere: 13.5 g ethyl ester of 2,2-dimethyl-3-((3-chloro-(3-trifluoromethyl-vinyl)-cyclopropanecarboxylic acid) (mixture of isomers)
5 ml tert.-butanol 5 ml tert.-butanol
5 ml vannfritt benzen. 5 ml anhydrous benzene.
Reaksjonsblandingen ble holdt ved 15 - 20° C ved kjøling med et eksternt bad av is og vann inntil all varmeutvikling hadde opphørt (ca. 1 time). Reaksjonsblandingen ble deretter oppvarmet ved tilbakeløpstemperatur i 6 timer. Etter kjøling ved romtemperatur ble den helt over i 100 ml av en 2N vandig oppløsning av hydrogenklorid. Den organiske fase ble deretter fraskilt, vasket med vann til nøyrral pH, tørret over Na-jSO^ og filtrert. Det organiske oppløsningsmiddel ble deretter fjernet under vakuum, hvorved det ble erholdt 12,5 g råprodukt som ble destillert ved hjelp av en 10 cm høy Vigreux-kolonne. Fraksjonen som kokte ved 93 - 93° C ved 3 5 mmHg ble oppsamlet. Den besto av det ønskede produkt (Forbindelse h i tabell 3). The reaction mixture was kept at 15 - 20° C by cooling with an external bath of ice and water until all heat development had ceased (approx. 1 hour). The reaction mixture was then heated at reflux temperature for 6 hours. After cooling at room temperature, it was poured into 100 ml of a 2N aqueous solution of hydrogen chloride. The organic phase was then separated, washed with water to neutral pH, dried over Na 2 SO 4 and filtered. The organic solvent was then removed under vacuum to give 12.5 g of crude product which was distilled using a 10 cm tall Vigreux column. The fraction boiling at 93-93°C at 35 mmHg was collected. It consisted of the desired product (Compound h in Table 3).
Ved sammenligning mellom NMR-dataene (se tabell 3) for forbindelse h og forbindelse f synes det klart at den sistnevnte er trans-isomeren. By comparing the NMR data (see Table 3) for compound h and compound f, it seems clear that the latter is the trans isomer.
Eksempel 8 Example 8
Fremstilling av ethylesteren av (+)- trans- 2, 2- dimethyl- 3-( g- tri-fluormethyl( Z) vinyl)- cyclopropancarboxylsyre ( forbindelse i i tabell 3) og den tilsvarende frie syre. ( forbindelse j i tabell 3) Preparation of the ethyl ester of (+)-trans-2,2-dimethyl-3-(g-trifluoromethyl(Z)vinyl)-cyclopropanecarboxylic acid (compound i in Table 3) and the corresponding free acid. (compound j in Table 3)
I en 500 ml's rundkolbe ble det under nitrogenatmosfære tilført: 11,5 g ethylester av 2,2-dimethyl-3-(3-trifluormethyl-ethynyl)-cyclopropancarboxylsyre (forbindelse f) In a 500 ml round flask, under a nitrogen atmosphere, 11.5 g of ethyl ester of 2,2-dimethyl-3-(3-trifluoromethyl-ethynyl)-cyclopropanecarboxylic acid (compound f) were added
200 ml n-hexan 200 ml of n-hexane
2 g palladium på calciumcarbonat (Pd/CaCC^) forgiftet med bly 2 g of palladium on calcium carbonate (Pd/CaCC^) poisoned with lead
(fremsilt i henhold til Organic Synthesis, Coll. Vol. V. 880, John Wiley & Son, 1973). (reprinted from Organic Synthesis, Coll. Vol. V. 880, John Wiley & Son, 1973).
Kolben ble deretter forbundet med et hydrogeneringsappa-rat, og kolbens innhold ble kraftig omrørt i noen timer, inntil intet hydrogen lenger ble absorbert. The flask was then connected to a hydrogenation apparatus, and the contents of the flask were vigorously stirred for a few hours, until no more hydrogen was absorbed.
Reaksjonsblandingen ble deretter filtrert på "Celite", The reaction mixture was then filtered on "Celite",
og oppløsningsmidlet ble avdrevet, hvorved det ble erholdt 10,5 g råprodukt som ble destillert ved redusert trykk. and the solvent was driven off, whereby 10.5 g of crude product was obtained which was distilled under reduced pressure.
Fraksjonen som kokte ved 88° C og 16 mmHg ble oppsamlet og analysert ved IR- og NMR-spektroskopi. Produktet viste seg å være forbindelse i (renhet _> 90 %), ved gass-væskekromatografi) . The fraction boiling at 88°C and 16 mmHg was collected and analyzed by IR and NMR spectroscopy. The product was found to be compound i (purity _> 90%), by gas-liquid chromatography).
Til 7 g av forbindelse i ble det tilsatt 4 g 85 % KOH og 50 ml 95 %-ig ethanol. Blandingen ble oppvarmet' med tilbakeløps-kjøling i 4 timer. Det meste av oppløsningsmidlet ble deretter avdrevet, og 50 ml vann ble tilsatt. Til denne blanding ble det satt 10 g av en vandig oppløsning av svovelsyre i forholdet 1:1, hvoretter blandingen ble ekstrahert med methylenklorid. Den organiske fase ble så tørret over vannfritt Na2S04 og filtrert. Etter avdrivning av oppløsningsmidlet under vakuum ble det erholdt 5,9 g av en olje, som etter krystallisering ved hjelp av n-pentan ga forbindelse j i form av et hvitt, fast stoff (sm.p. 49 - 50° C). To 7 g of compound i was added 4 g of 85% KOH and 50 ml of 95% ethanol. The mixture was heated under reflux for 4 hours. Most of the solvent was then driven off and 50 ml of water was added. To this mixture was added 10 g of an aqueous solution of sulfuric acid in the ratio 1:1, after which the mixture was extracted with methylene chloride. The organic phase was then dried over anhydrous Na 2 SO 4 and filtered. After stripping off the solvent under vacuum, 5.9 g of an oil were obtained, which after crystallization with the aid of n-pentane gave compound j in the form of a white solid (m.p. 49 - 50° C).
Eksempel 9 Example 9
Fremstilling av ethylesteren av 2, 2- dimethyl- 3-( 2- klor- 3, 3, 3-trifluor- propyl)- cyclopropancarboxylsyre Preparation of the ethyl ester of 2,2-dimethyl-3-(2-chloro-3,3,3-trifluoro-propyl)-cyclopropanecarboxylic acid
I et "Pyrex"-glass for reaksjoner under trykk ble de følgende reaktanter innført under nitrogenatmosfære: 15,6 g (0,1 mol) av ethylesteren av 3,3-dimethyl-4-pentensyre 59,2 g (0,3 mol) 1,1,1-trifluor-klorbromethan Into a "Pyrex" glass for reactions under pressure, the following reactants were introduced under a nitrogen atmosphere: 15.6 g (0.1 mol) of the ethyl ester of 3,3-dimethyl-4-pentenoic acid 59.2 g (0.3 mol ) 1,1,1-trifluorochlorobromoethane
3 ml ethanolamin 0,6 g CuCl 3 ml ethanolamine 0.6 g CuCl
Glassrøret ble deretter flammeforseglet og rystet.for å opprettholde en homogen blanding. Den ble så innført i en auto--klav fyllt med vann inntil 2/3 av dens volum. Autoklaven ble lukket og oppvarmet ved 120 - 140° C i 20 timer. Etter nedkjøling ble glassrøret åpnes og overskuddet av 1,1,1-trifluor-klorbromethan destillert under vakuum. Residuet ble oppsamlet med diethylether, vasket med en 2N oppløsning av hydrogenklorid og deretter, med vann til nøytral pH, hvorpå blandingen ble filtrert. Den organiske fase ble tørret over vannfritt Na^SO^, og oppløsningsmidlet ble fjernet under vakuum. Residuet ble destillert ved nedsatt trykk, og fraksjonen . som kokte ved 79 - 75° C ved 0,06 mmHg ble oppsamlet, denne besto av 20 g av ethylesteren av 3,3-dimethyl-4-brom-6-klor-7,7,7-trifluorheptansyre (nQ 24 = 1,4415, elementar-analyse, IR- og NMR-spektret stemte med den antatte struktur). 10 g av dette mellomprodukt ble oppløst i 10 ml absolutt ethanol, og den erholdte oppløsning ble ved romtemperatur tilsatt til en oppløsning av natriumethylat fremstilt ved oppløsning av 1,5 g natrium i 55 ml absolutt ethanol. Reaksjonsblandingen ble deretter oppvarmet med tilbakeløpskjøling i 1,5 timer, hvoretter oppløsningsmidlet ble avdrevet under vakuum og 100 ml vann ble tilsatt residuet. Det organiske materiale ble ekstrahert med 3 x 75 ml diethylether. The glass tube was then flame-sealed and shaken to maintain a homogeneous mixture. It was then introduced into an autoclave filled with water up to 2/3 of its volume. The autoclave was closed and heated at 120 - 140° C. for 20 hours. After cooling, the glass tube was opened and the excess of 1,1,1-trifluorochlorobromoethane distilled under vacuum. The residue was taken up with diethyl ether, washed with a 2N solution of hydrogen chloride and then, with water to neutral pH, after which the mixture was filtered. The organic phase was dried over anhydrous Na 2 SO 4 , and the solvent was removed under vacuum. The residue was distilled under reduced pressure, and the fraction . which boiled at 79 - 75° C at 0.06 mmHg was collected, this consisted of 20 g of the ethyl ester of 3,3-dimethyl-4-bromo-6-chloro-7,7,7-trifluoroheptanoic acid (nQ 24 = 1 ,4415, elemental analysis, the IR and NMR spectrum agreed with the assumed structure). 10 g of this intermediate product was dissolved in 10 ml of absolute ethanol, and the resulting solution was added at room temperature to a solution of sodium ethylate prepared by dissolving 1.5 g of sodium in 55 ml of absolute ethanol. The reaction mixture was then heated under reflux for 1.5 hours, after which the solvent was evaporated under vacuum and 100 ml of water was added to the residue. The organic material was extracted with 3 x 75 ml of diethyl ether.
Den organiske fase ble deretter vasket med vann til nøy-tral pH og tørret over vannfritt Na-jSO^, og oppløsningsmidlet ble avdrevet under vakuum. Derved ble det erholdt 6,3 g av ethylesteren av 2,2-dimethyl-3-(2-klor-3,3,3-trifluorpropyl)-cyclopropancarboxylsyre som en blanding av cis- og trans-isomere (ca. 1:1) The organic phase was then washed with water to neutral pH and dried over anhydrous Na 2 SO 4 , and the solvent was evaporated under vacuum. Thereby 6.3 g of the ethyl ester of 2,2-dimethyl-3-(2-chloro-3,3,3-trifluoropropyl)-cyclopropanecarboxylic acid were obtained as a mixture of cis- and trans-isomers (approx. 1:1 )
(forbindelse k i tabell 3). (compound k in Table 3).
Eksempel 10 Fremstilling av ethylesteren av ( + )- cis, trans- 2, 2- dimethyl- 3-(( 3-trifluormethyl- E- vinyl)- cyclopropancarboxylsyre. Example 10 Preparation of the ethyl ester of (+)-cis, trans-2,2-dimethyl-3-((3-trifluoromethyl-E-vinyl)-cyclopropanecarboxylic acid.
2,5 g C2H5ONa ble ved -15° C oppløst i 80 ml diméthyl-formamid. Til denne oppløsning ble det tilsatt 6,3 g av ethylesteren av (+)-cis, trans-2,2-dimethyl-3-(2-klor-3,3,3-trifluor-propyl ) -cyclopropancarboxylsyre i 20 ml dimethylformamid. 2.5 g of C2H5ONa were dissolved at -15° C in 80 ml of dimethylformamide. To this solution was added 6.3 g of the ethyl ester of (+)-cis, trans-2,2-dimethyl-3-(2-chloro-3,3,3-trifluoro-propyl)-cyclopropanecarboxylic acid in 20 ml of dimethylformamide .
Reaksjonsblandingen ble langsomt oppvarmet fra -15 til 0° C i løpet av 3 timer, hvoretter det ble tilsatt 100 ml vann av 0° C. Det organiske materiale ble så ekstrahert med 3 - 100 ml diethylether. Den organiske oppløsning ble vasket med vann til nøytral pH og tørret med vannfritt CaCl2, hvoretter oppløsnings-midlet ble fjernet under vakuum. Derved fikk man 5 g av ethylesteren av (+)-cis, trans-2 , 2-dimethyl-3-((3-trif luormethyl-E-vinyl )-cyclopropancarboxylsyre som en blanding av cis-trans-isomere i et mengdeforhold av ca. 1:1 (forbindelse 1 i tabell 3). The reaction mixture was slowly heated from -15 to 0° C. over 3 hours, after which 100 ml of 0° C. water was added. The organic material was then extracted with 3 - 100 ml of diethyl ether. The organic solution was washed with water to neutral pH and dried with anhydrous CaCl 2 , after which the solvent was removed under vacuum. Thereby, 5 g of the ethyl ester of (+)-cis, trans-2, 2-dimethyl-3-((3-trifluoromethyl-E-vinyl)-cyclopropanecarboxylic acid was obtained as a mixture of cis-trans isomers in a quantity ratio of about 1:1 (compound 1 in Table 3).
Den samme reaksjon ble utført også ved 0° C i 15 timer. Derved.fikk man.et produkt som for ca. 90 % vedkommende besto av trans-isomeren, hvilket viste seg ved at sigrtalet ved 1,85 ppm i nmr-spekteret, svarende til protonet HQ i cis-isomeren, forsvant (se tabell 3) . The same reaction was also carried out at 0° C. for 15 hours. This resulted in a product that for approx. 90% of which consisted of the trans isomer, which was shown by the sigr number at 1.85 ppm in the nmr spectrum, corresponding to the proton HQ in the cis isomer, disappearing (see table 3).
Eksempel 11 Example 11
Fremstilling av CF3-CFBr-CH2-CHBr-C(CH3)2~CH(C02C2H5)2Preparation of CF3-CFBr-CH2-CHBr-C(CH3)2~CH(C02C2H5)2
I en 250 ml "Hastelloy C" autoklav utstyrt med en vugge-innretning ble det under nitrogenatmosfære tilsatt: In a 250 ml "Hastelloy C" autoclave equipped with a cradle device, under nitrogen atmosphere was added:
2 08 g CF3-CFBr2 (0,8 mol) 2 08 g CF3-CFBr2 (0.8 mol)
91,2 g CH2=CH-C(CH3)2-CH(C02Et)2 (0,4 mol) 91.2 g CH2=CH-C(CH3)2-CH(CO2Et)2 (0.4 mol)
6 ml di-tert.-butylperoxyd. 6 ml of di-tert-butyl peroxide.
Autoklaven ble oppvarmet til 14 0° C og holdt ved denne temperatur i 2 timer. Etter kjøling ble innholdet tatt ut, og overskuddet av CF3~CFBr2 ble fjernet ved fordampning, hvoretter innholdet i autoklaven ble underkastet molekylar_xlestillasjon. Fraksjonen med kokepunkt 90° C ved IO<-3> mmHg ble oppsamlet. Den besto av 120 g ethyl-(1,l-dimethyl-2,4-dibrom-4,5,5,5-tetrafluor)-pentyl-malonat. The autoclave was heated to 140°C and held at this temperature for 2 hours. After cooling, the contents were taken out, and the excess of CF3~CFBr2 was removed by evaporation, after which the contents of the autoclave were subjected to molecular_xlestillation. The fraction with a boiling point of 90° C. at 10<-3> mmHg was collected. It consisted of 120 g of ethyl-(1,1-dimethyl-2,4-dibromo-4,5,5,5-tetrafluoro)pentyl malonate.
22° 22°
n^ = 1,4513 . n^ = 1.4513 .
IR-analysen stemte med den angitte struktur. The IR analysis agreed with the indicated structure.
Elementæranalyse: C funnet = 34,9 %, teoretisk C = 34,5 % Elemental analysis: C found = 34.9%, theoretical C = 34.5%
H funnet = 4,2 %, teoretisk H = 4,1 % H found = 4.2%, theoretical H = 4.1%
F funnet = 15,4 %, teoretisk F = 15,6 % F found = 15.4%, theoretical F = 15.6%
Br funnet= 31,9 %, teoretisk Br= 32,8 % Br found= 31.9%, theoretical Br= 32.8%
E ksempel 12 Example 12
48,8 g (0,1 mol) ethyl-(1,l-dimethyl-2,4-dibrom-4,5,5,5-tetrafluor)-pentyl-malonat, fremstilt som beskrevet i eksempel 11, i 100 ml vannfri ethanol ble tilsatt dråpevis og under omrøring til en ethanoloppløsning av natriumethylat, fremstilt ut fra 2,4 g natrium og 100 ml vannfri ethanol. 48.8 g (0.1 mol) ethyl-(1,1-dimethyl-2,4-dibromo-4,5,5,5-tetrafluoro)-pentyl malonate, prepared as described in example 11, in 100 ml anhydrous ethanol was added dropwise and with stirring to an ethanol solution of sodium ethylate, prepared from 2.4 g of sodium and 100 ml of anhydrous ethanol.
Etter fullført tilsetning ble det fra blandingen tatt ut en prøve, som ble gass-masse-analysert. Resultatene viste at ringslutningsreaksjonen allerede var fullført under dannelse av forbindelsen: After completion of the addition, a sample was taken from the mixture, which was gas-mass-analysed. The results showed that the cyclization reaction had already been completed to form the compound:
Masse-fragmentering: Mass fragmentation:
(<C>14H19F4Br04): 406 (M<+>) (<C>14H19F4Br04): 406 (M<+>)
327 (M<+->Br) 327 (M<+->Br)
361 (M<+->C2H50) 361 (M<+->C2H50)
213 (M<+->C3F4BrH2) 213 (M<+->C3F4BrH2)
315 315
314 314
185 185
167 167
43 43
På dette tidspunkt ble det tilsatt en ytterligere mengde natriumethylat i ethanol (like stor som den foregående), og reaksjonsblandingen ble omrørt ved 40° C i 5 timer. At this point, a further amount of sodium ethylate in ethanol (equal to the previous one) was added and the reaction mixture was stirred at 40°C for 5 hours.
Etter nøytralisering med HC1 (1:1) og påfølgende filtre-ring ble oppløsningen konsentrert til et lite volum, tilsatt 200 ml vann og deretter ekstrahert med CHCl^ (2 x 150 ml). Kloroformr ekstrakten ble deretter gjort vannfri med CaCl2 og så inndampet, hvorved man fikk 31,4 g av diethylesteren av 2,2-dimethyl-3-(3-fluor-3-trifluormethyl-vinyl)-cyclopropan-1,1-dicarboxylsyre, After neutralization with HCl (1:1) and subsequent filtration, the solution was concentrated to a small volume, 200 ml of water was added and then extracted with CHCl 2 (2 x 150 ml). The chloroform extract was then made anhydrous with CaCl2 and then evaporated to give 31.4 g of the diethyl ester of 2,2-dimethyl-3-(3-fluoro-3-trifluoromethyl-vinyl)-cyclopropane-1,1-dicarboxylic acid,
22° 22°
n = 1,4303 n = 1.4303
D D
Massefragmentering: Mass fragmentation:
(<C>14H18F4°4)<:> 326'(M<+>) (<C>14H18F4°4)<:> 326'(M<+>)
281 (M<+->CoHc0) 281 (M<+->CoHc0)
+ 2 5 + 2 5
253 (M -C3H502) 253 (M -C3H502)
225 (253-C2H4) 225 (253-C2H4)
235 235
207 207
179 179
167 167
160 160
115 115
Eksempel 13 Example 13
I en kolbe som var neddykket i et oljebad og som var utstyrt med en tilbakeløpskjøler, ble det under nitrogenatmosfære In a flask immersed in an oil bath and equipped with a reflux condenser, under a nitrogen atmosphere
•i nn f oirt : •in nn f oirt :
1 g Na cl 1 g Nacl
12 ml dimethylsulfoxyd 12 ml of dimethylsulfoxide
0,6 ml vann. 0.6 ml of water.
Reaksjonsblandingen ble deretter oppvarmet med_ til-bakeløpsk jøling i 9 timer ved 165 - 167° C. Etter avkjøling viste det seg ved gasskromatografisk analyse at forbindelsen var blitt dannet med en omdannelsesgrad av 75 % og med et cis/trans-forhold på ca. 1:1 for ringens vedkommende. The reaction mixture was then heated with reflux for 9 hours at 165 - 167° C. After cooling, gas chromatographic analysis showed that the compound had been formed with a degree of conversion of 75% and with a cis/trans ratio of approx. 1:1 for the ring.
Eksempel i4 Example i4
Fremstilling av CF3-CC12-CH2-CHC1-C(CH3)2~CH(C02C2H5)2Preparation of CF3-CC12-CH2-CHC1-C(CH3)2~CH(C02C2H5)2
I en mekanisk omrørt autoklav av "Hastelloy-C" ble det i nitrogenatmosfære innført: In a mechanically stirred "Hastelloy-C" autoclave, in a nitrogen atmosphere, were introduced:
23 g CH2=CH-C(CH3)2-CH(C02C2H5)2 (0,1 mol) 23 g CH2=CH-C(CH3)2-CH(C02C2H5)2 (0.1 mol)
82,5 g CF3-CC13 (0,4 mol) 82.5 g CF3-CC13 (0.4 mol)
0,16 g CuCl 0.16 g of CuCl
3,5 g ethanolamin 3.5 g ethanolamine
115 ml tert.-butylalkohol 115 ml tert-butyl alcohol
Autoklaven ble oppvarmet ved 100° C i 2 timer og deretter ved 110° C i ytterligere 7 timer. Etter avkjøling ble reaksjonsblandingen filtrert, og etter fjerning av overskuddet av CF3CC13 ved fordampning ble oppløsningen destillert ved nedsatt trykk. Derved fikk man 20 g av en fraksjon med k.p. l-05°C/0,05 mmHg, bestående av ethyl-(1,l-dimethyl-2,4,4-triklor-5,5,5-trifluor)-pentyl-malonat. The autoclave was heated at 100° C. for 2 hours and then at 110° C. for a further 7 hours. After cooling, the reaction mixture was filtered, and after removing the excess of CF 3 CC 3 by evaporation, the solution was distilled under reduced pressure. This resulted in 20 g of a fraction with b.p. 1-05°C/0.05 mmHg, consisting of ethyl-(1,1-dimethyl-2,4,4-trichloro-5,5,5-trifluoro)-pentyl malonate.
IR (ren prøve) : • 172 0 og 1740 cm<-1> (C=0); andre bånd ved : 1460, 1362, 1300, 1255, 1227, 1205, IR (pure sample) : • 172 0 and 1740 cm<-1> (C=0); other bands at: 1460, 1362, 1300, 1255, 1227, 1205,
1175, 1040 cm"<1>. 1175, 1040 cm"<1>.
Elementæranalyse: y Elementary analysis: y
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IT2071478A IT1095450B (en) | 1978-02-28 | 1978-02-28 | 3-Poly:fluoro-propyl cyclopropane-carboxylate ester derivs. - with insecticidal and acaricidal activities |
IT20713/78A IT1095449B (en) | 1978-02-28 | 1978-02-28 | NEW PYRETROIDS |
IT3131078A IT1160403B (en) | 1978-12-27 | 1978-12-27 | 3-Poly:fluoro-propyl cyclopropane-carboxylate ester derivs. - with insecticidal and acaricidal activities |
IT1970379A IT1166603B (en) | 1979-01-30 | 1979-01-30 | 3-Poly:fluoro-propyl cyclopropane-carboxylate ester derivs. - with insecticidal and acaricidal activities |
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NO792716A NO153098C (en) | 1978-02-28 | 1979-08-21 | 3-SUBSTITUTED 2,2-DIMETHYL-CYCLOPROPANCARBOXYL ACIDES AND LOWER ALKYLESTERS THEREOF USE AS OUTSIDE MATERIALS IN THE PREPARATION OF PYRETHROIDS WITH INSECTICID EFFECT |
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO790621A NO152582C (en) | 1978-02-28 | 1979-02-23 | INSECTICID AGENT CONTAINING AS ACTIVE COMPONENT ONE OR MORE 3-SUBSTITUTED 2,2-DIMETHYL-CYCLOPROPANCARBOXYL ACID ESTERS |
Country Status (28)
Country | Link |
---|---|
JP (1) | JPS54130537A (en) |
AR (1) | AR241108A1 (en) |
AU (1) | AU531296B2 (en) |
BE (1) | BE874515A (en) |
BG (3) | BG48921A3 (en) |
BR (1) | BR7901221A (en) |
CA (1) | CA1237439A (en) |
CH (1) | CH638485A5 (en) |
DD (2) | DD148767A5 (en) |
DE (1) | DE2907609A1 (en) |
DK (1) | DK161830C (en) |
ES (1) | ES478426A1 (en) |
FR (1) | FR2442826A1 (en) |
GB (1) | GB2015519B (en) |
GR (1) | GR72544B (en) |
HU (1) | HU185607B (en) |
IL (1) | IL56739A0 (en) |
IN (1) | IN150228B (en) |
KE (1) | KE3293A (en) |
LU (1) | LU80981A1 (en) |
MX (1) | MX5698E (en) |
NL (1) | NL7901460A (en) |
NO (2) | NO152582C (en) |
NZ (1) | NZ189791A (en) |
PL (1) | PL135350B1 (en) |
PT (1) | PT69283A (en) |
RO (1) | RO77772A (en) |
YU (1) | YU48279A (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2831193A1 (en) * | 1978-07-15 | 1980-01-24 | Bayer Ag | FLUORALKENYL-SUBSTITUTED CYCLOPROPANCARBONIC ACID ESTERS AND THEIR USE AS INSECTICIDES |
DE2965744D1 (en) * | 1978-10-27 | 1983-07-28 | Ici Plc | Process for separating optical isomers of substituted cyclopropane carboxylic acids; amine salts of substituted cyclopropane carboxylic acids; a substituted cyclopropane carboxylic acid |
DE2919820A1 (en) * | 1979-05-16 | 1980-11-20 | Bayer Ag | FLUOR-SUBSTITUTED OXYALKENYL-CYCLOPROPANCARBONIC ACID ESTERS, METHODS FOR THE PRODUCTION THEREOF AND THEIR USE AS INSECTICIDES AND ACARICIDES |
DE3064018D1 (en) * | 1979-07-13 | 1983-08-11 | Ici Plc | Process for the preparation of cyclopropane carboxylic acid esters |
IT1131883B (en) * | 1980-07-02 | 1986-06-25 | Montedison Spa | INTERMAEDI PROCESS FOR STEREOSELECTIVE SYNTHESIS OF CYCLOPROPANCARBOXYLATES FOR PYRETROIDS |
NZ221534A (en) * | 1986-08-27 | 1990-10-26 | Montedison Spa | Derivatives of 2,2-dimethyl-cyclopropane carboxylic acid; insecticides and acaricides |
DE3900275A1 (en) * | 1989-01-07 | 1990-07-12 | Basf Ag | SUBSTITUTED CYCLOPROPANCARBONIC ACID PROPARGYL ESTERS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE FOR CONTROLLING Pests |
FR2687152A1 (en) * | 1992-02-07 | 1993-08-13 | Roussel Uclaf | NOVEL PYRETHRINOUID ESTERS DERIVED FROM FURANIC OR THIOPHENIC ALCOHOL, PROCESS FOR THEIR PREPARATION AND THEIR USE AS PESTICIDES |
US6072074A (en) * | 1998-05-08 | 2000-06-06 | Sumitomo Chemical Company Limited | Process for producing 3-propynyl-2-2-dimethylcycloprophane-carboxylic acid and its lower akyl esters |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS515450B1 (en) | 1971-06-29 | 1976-02-20 | ||
DE2326077C2 (en) | 1972-05-25 | 1985-12-12 | National Research Development Corp., London | Unsaturated cyclopropanecarboxylic acids and their derivatives, their preparation and insecticides containing them |
JPS5283720A (en) * | 1976-01-01 | 1977-07-12 | Kuraray Co Ltd | Substituted cyclopropanecarboxylic acid derivatives, and insecticides and acaricides containing a-substituted cyclopropanecarboxylic acid deri vatives |
US4130655A (en) * | 1976-07-12 | 1978-12-19 | Ciba-Geigy Corporation | Pesticidal 2,2-dimethyl-3-isobutyl-cyclopropionates |
DE2638356A1 (en) * | 1976-08-26 | 1978-03-02 | Bayer Ag | METHOD FOR PRODUCING VINYL-SUBSTITUTED CYCLOPROPANCARBONIC ACID ESTERS |
US4183948A (en) * | 1977-01-24 | 1980-01-15 | Imperial Chemical Industries Limited | Halogenated esters |
GB2008572B (en) * | 1977-11-28 | 1982-01-27 | Ici Ltd | Manufacture of esters |
IN150399B (en) * | 1978-01-20 | 1982-09-25 | Fmc Corp |
-
1979
- 1979-02-06 BG BG44136/79A patent/BG48921A3/en unknown
- 1979-02-06 BG BG44135/79A patent/BG48333A3/en unknown
- 1979-02-23 NL NL7901460A patent/NL7901460A/en not_active Application Discontinuation
- 1979-02-23 NO NO790621A patent/NO152582C/en unknown
- 1979-02-23 BR BR7901221A patent/BR7901221A/en unknown
- 1979-02-23 DK DK080379A patent/DK161830C/en not_active IP Right Cessation
- 1979-02-26 GR GR58472A patent/GR72544B/el unknown
- 1979-02-26 IN IN173/CAL/79A patent/IN150228B/en unknown
- 1979-02-26 IL IL56739A patent/IL56739A0/en not_active IP Right Cessation
- 1979-02-26 PT PT69283A patent/PT69283A/en unknown
- 1979-02-26 BG BG42659A patent/BG48931A3/en unknown
- 1979-02-27 AU AU44631/79A patent/AU531296B2/en not_active Expired
- 1979-02-27 YU YU00482/79A patent/YU48279A/en unknown
- 1979-02-27 GB GB7906851A patent/GB2015519B/en not_active Expired
- 1979-02-27 HU HU79MO1039A patent/HU185607B/en unknown
- 1979-02-27 FR FR7904952A patent/FR2442826A1/en active Granted
- 1979-02-27 DE DE19792907609 patent/DE2907609A1/en active Granted
- 1979-02-27 ES ES478426A patent/ES478426A1/en not_active Expired
- 1979-02-27 CA CA000322525A patent/CA1237439A/en not_active Expired
- 1979-02-27 DD DD79218658A patent/DD148767A5/en not_active IP Right Cessation
- 1979-02-27 DD DD79211259A patent/DD142281A5/en not_active IP Right Cessation
- 1979-02-27 CH CH194279A patent/CH638485A5/en unknown
- 1979-02-27 PL PL1979213760A patent/PL135350B1/en unknown
- 1979-02-28 BE BE0/193748A patent/BE874515A/en not_active IP Right Cessation
- 1979-02-28 MX MX797764U patent/MX5698E/en unknown
- 1979-02-28 AR AR275649A patent/AR241108A1/en active
- 1979-02-28 NZ NZ189791A patent/NZ189791A/en unknown
- 1979-02-28 LU LU80981A patent/LU80981A1/en unknown
- 1979-02-28 RO RO79101065A patent/RO77772A/en unknown
- 1979-02-28 JP JP2204779A patent/JPS54130537A/en active Granted
- 1979-08-21 NO NO792716A patent/NO153098C/en unknown
-
1983
- 1983-06-08 KE KE3293A patent/KE3293A/en unknown
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