CN1049426C - 苯乙酸衍生物及其制备方法和用途 - Google Patents
苯乙酸衍生物及其制备方法和用途 Download PDFInfo
- Publication number
- CN1049426C CN1049426C CN93121110A CN93121110A CN1049426C CN 1049426 C CN1049426 C CN 1049426C CN 93121110 A CN93121110 A CN 93121110A CN 93121110 A CN93121110 A CN 93121110A CN 1049426 C CN1049426 C CN 1049426C
- Authority
- CN
- China
- Prior art keywords
- acid
- alkyl
- formula
- reaction
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 title description 2
- 239000002253 acid Substances 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 150000002790 naphthalenes Chemical class 0.000 claims abstract description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 5
- 238000006243 chemical reaction Methods 0.000 claims description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- -1 methylenedioxy Chemical group 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000003513 alkali Substances 0.000 claims description 12
- 235000019439 ethyl acetate Nutrition 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 6
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 235000015320 potassium carbonate Nutrition 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- CVVYLFDCAKERAT-UHFFFAOYSA-N C=C1CC=CC=C1.[O] Chemical compound C=C1CC=CC=C1.[O] CVVYLFDCAKERAT-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
- VDEUYMSGMPQMIK-UHFFFAOYSA-N benzhydroxamic acid Chemical compound ONC(=O)C1=CC=CC=C1 VDEUYMSGMPQMIK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000007127 saponification reaction Methods 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical group OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 229960003424 phenylacetic acid Drugs 0.000 claims description 2
- 239000003279 phenylacetic acid Substances 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 238000007039 two-step reaction Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 6
- 230000003641 microbiacidal effect Effects 0.000 abstract description 5
- 229940124561 microbicide Drugs 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- XIQGPUDEPHSVFJ-UHFFFAOYSA-N 2-[6-(aminooxymethylidene)cyclohexa-2,4-dien-1-yl]acetic acid Chemical class NOC=C1C=CC=CC1CC(O)=O XIQGPUDEPHSVFJ-UHFFFAOYSA-N 0.000 abstract 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
- 150000007513 acids Chemical class 0.000 abstract 1
- 239000012458 free base Substances 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
- 239000000243 solution Substances 0.000 description 14
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 150000002923 oximes Chemical class 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229960001866 silicon dioxide Drugs 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 3
- 239000002855 microbicide agent Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 229940071870 hydroiodic acid Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- XEMRAKSQROQPBR-UHFFFAOYSA-N (trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=CC=C1 XEMRAKSQROQPBR-UHFFFAOYSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- SEQRDAAUNCRFIT-UHFFFAOYSA-N 1,1-dichlorobutane Chemical compound CCCC(Cl)Cl SEQRDAAUNCRFIT-UHFFFAOYSA-N 0.000 description 1
- WQONPSCCEXUXTQ-UHFFFAOYSA-N 1,2-dibromobenzene Chemical compound BrC1=CC=CC=C1Br WQONPSCCEXUXTQ-UHFFFAOYSA-N 0.000 description 1
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- ABXGMGUHGLQMAW-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C(F)(F)F)=C1 ABXGMGUHGLQMAW-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
- NVJUHMXYKCUMQA-UHFFFAOYSA-N 1-ethoxypropane Chemical compound CCCOCC NVJUHMXYKCUMQA-UHFFFAOYSA-N 0.000 description 1
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical group CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical compound CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 1
- WBUOVKBZJOIOAE-UHFFFAOYSA-N 3-chlorobenzonitrile Chemical compound ClC1=CC=CC(C#N)=C1 WBUOVKBZJOIOAE-UHFFFAOYSA-N 0.000 description 1
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000370738 Chlorion Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- AQZGPSLYZOOYQP-UHFFFAOYSA-N Diisoamyl ether Chemical compound CC(C)CCOCCC(C)C AQZGPSLYZOOYQP-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- QQZWEECEMNQSTG-UHFFFAOYSA-N Ethyl nitrite Chemical compound CCON=O QQZWEECEMNQSTG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000004705 aldimines Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001341 alkaline earth metal compounds Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- MNCHTHBKZOMDQI-UHFFFAOYSA-N cyclopropyl(2,3-dihydro-1,4-benzodioxin-6-yl)methanone Chemical compound C=1C=C2OCCOC2=CC=1C(=O)C1CC1 MNCHTHBKZOMDQI-UHFFFAOYSA-N 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- YWOITFUKFOYODT-UHFFFAOYSA-N methanol;sodium Chemical compound [Na].OC YWOITFUKFOYODT-UHFFFAOYSA-N 0.000 description 1
- GHDIHPNJQVDFBL-UHFFFAOYSA-N methoxycyclohexane Chemical compound COC1CCCCC1 GHDIHPNJQVDFBL-UHFFFAOYSA-N 0.000 description 1
- OFXSXYCSPVKZPF-UHFFFAOYSA-N methoxyperoxymethane Chemical compound COOOC OFXSXYCSPVKZPF-UHFFFAOYSA-N 0.000 description 1
- XNXPIAADLKVNFE-UHFFFAOYSA-N methyl 2-hydroxyprop-2-enoate Chemical class COC(=O)C(O)=C XNXPIAADLKVNFE-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- BSDQITJYKQHXQR-UHFFFAOYSA-N methyl prop-2-eneperoxoate Chemical compound COOC(=O)C=C BSDQITJYKQHXQR-UHFFFAOYSA-N 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- BNIXVQGCZULYKV-UHFFFAOYSA-N pentachloroethane Chemical compound ClC(Cl)C(Cl)(Cl)Cl BNIXVQGCZULYKV-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- FLTJDUOFAQWHDF-UHFFFAOYSA-N trimethyl pentane Natural products CCCCC(C)(C)C FLTJDUOFAQWHDF-UHFFFAOYSA-N 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
式I的2-氨氧亚甲基苯乙酸酯衍生物游离碱及与质子酸所成盐为制备有益保护植物的杀微生物剂的重要中间体。
式中，Z1和Z2为氢、卤原子、羟基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1-C4卤代烷氧基、C1-C4烷基羰基、C1-C4烷氧羰基、苯氧基、硝基、氰基，Z和Z2与所连苯基一起为萘或氢化萘；R3为氢或C1-C12烷基。
本发明还涉及式I化合物的简化制备方法及从这些中间体合成杀微生物剂的方法。
Description
本发明是关于式I的2-氨氧亚甲基苯乙酸酯衍生物游离碱或与质子酸所成的盐，关于此化合物的制备方法及用来合成有益保护植物的式VI杀微生物剂的用途。上式中：Z1和Z2为氢、卤原子、羟基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1-C4卤代烷氧基、C1-C4烷基羰基、C1-C4烷氧羰基、苯氧基、硝基、氰基、Z1和Z2与所连苯基一起为萘或氢化萘，及R3为氢或C1-C12烷基。
适合的盐为与HY酸所成的盐，其中Y为酸的阴离子，典型的酸有盐酸、氢溴酸、氢碘酸、高氯酸、取代或未取代的苯磺酸、甲磺酸、三氟甲磺酸、四氟硼酸、六氟磷酸、磷酸、硫酸、亚硫酸、一般羧酸(如甲酸、乙酸、三氟乙酸等)。优选无机酸，特别是盐酸和硫酸。
本发明的方法是按路线1，由A步反应(取代的邻甲苯基乙酸酯II与苯甲酰羟胺III反应，生成苯甲酰化的2-氨氧亚甲基苯乙酸酯IV)和B步反应(酸皂化(水解)生成最终产品I)组成，路线1在上式中，U为离核离去基团，R3、Z1和Z2如上所定义，Z3、Z4和Z5可相同或不同，为氢、直链或支链C1-C6烷基、卤原子、羟基、直链或支链C1-C6烷氧基、硝基、氰基、N(R5)2、SO2NH2、取代或未取代的苯氧基、CF3、疏基、两R5取代基可相同或不同，为氢和/或直链或支链C1-C6烷基，及Z3和Z4也可以在连位一起形成一个亚甲二氧桥，或与所连结苯环一起可形成萘环。
优选Z3、Z4和Z5取代基为氢、甲基和卤原子，氢原子最优选。R3优选为卤原子或C1-C4烷基，最优选为甲基。
适合的离核离去基团U为卤离子，特别是氯离子、溴离子或碘离子，及苯磺酸根、甲苯磺酸根、甲磺酸根、三氟甲磺酸根、或乙酸根。溴离子尤为优选。
在A步和B步反应中使用稀释剂并在0℃到反应混合物沸点的温度范围内完成反应是有利的。
A步反应中加入无机或有机碱或混合碱是有用的，而B步水解反应在酸性条件下完成。
本发明的新方法的特色在于反应物易得、制备反应温和及惊人的高产率，甚至在式II的起始原料用不纯的粗品时也是如此。因此本方法，对简化WO 90/07493、EP-A-370629、EP-A-414153、EP-A-426 460、EP-A-460575、EP-A-463 488、EP-A-472 300、WO 92/18494、WO 92/18487中公开的杀微生物剂2-苯基丙烯酸酯、2-苯基烷氧基丙烯酸酯及苯基甲氧亚胺基乙酸酯的合成有实质性贡献。
这样得到的式I化合物可以用碱或盐的形式与式V的醛亚胺或酮亚胺衍生物相对应的醛或酮反应，再用一般方法在乙酯侧连进一步反应就得到上所边引述文献描述的杀微生物剂(反应步骤C和D)：上式VI中，X为CHO(C1-C4烷基)、NO(C1-C4烷基)、未取代的CH2或以其它方式取代的CH2；R1和R2可相同或不同，为氢、氰基、直链或支链C1-C10烷基、C1-C4卤代烷基、C3-C6环烷基、C3-C6卤代环烷基、C3-C6环烷基-C1-C4烷基、C1-C4烷氧基-C1-C4烷基、C1-C4烷基硫-C1-C4烷基、芳基硫-C1-C4烷基、C2-C6链烯基、C2-C5卤代链烯基、C3-C6环烯基、C3-C6卤代环烯基、C2-C6链炔基、C1-C6烷氧基、C1-C6卤代烷氧基、C1-C4烷硫基、苯甲硫基、C1-C4烷基羰基、取代或未取代的苯基羰基、取代或未取代的苄基羰基、C1-C4烷氧羰基、取代或未取代的苯氧羰基、取代或未取代的苄氧羰基、取代或未取代的芳基、取代或未取代的芳氧基、取代或未取代的芳硫基、取代或未取代的芳基-C1-C4烷基、取代或未取代的芳基-C1-C4链烯基、取代或未取代的芳氧基-C1-C4烷基、取代或未取代的芳硫基-C1-C4烷基、取代或未取代的杂芳基、取代或未取代的杂芳氧基、取代或未取代的杂芳硫基、取代或未取代的杂芳基-C1-C4烷基、取代或未取代的杂芳基-C2-C4链烯基、取代或未取代的杂芳氧基-C1-C4烷基、取代或未取代的杂环基、取代或未取代的杂环氧基、取代或未取代的杂环基烷基、N(R4)2、其中两个R4可相同或不同，为H、C1-C6烷基、取代或未取代的苯基、或两R4取代基与所连氮原子一起形成5到7元可含杂原子的取代或未取代的环；或R1和R2为-CON(R4)2、硝基、卤原子、-S(O)nR4，其中n为0、1、或2，或为(CH2)mPO(OR4)2，其中m为0或1，或R1和R2一起形成取代或未取代的碳环或杂环，及R3、Z1和Z2如式I中所定义。
本发明还涉及通式IV、I和V的中间体按反应步骤A、B、C和D制备式VI的化合物。
因此，本发明还涉及上边所定义的式VI的化合物的制备方法，包括：A)式II取代的邻甲苯乙酸酯
与苯甲酰羟胺III反应，
B)将所得式IV的苯甲酰化的2-氨氧亚甲基苯乙酸酯用酸HY进行酸皂化，C)式I的2-氨氧亚甲基苯乙酸酯与酮R1-CO-R2反应，及D)将生成的中间体V的乙酸酯侧链
转变为侧链，其中X为任意C1-C4烷基-O-CH或C1-C4烷基-O-N，及Z1到Z5和R1到R3及U如关于上式I到V所定义，Y为酸的阴离子。
已有技术文献提出了合成式VI的化合物的下列复杂反应路线，结果产率很低(反应不完全；副反应)。路线II：
或b)
与之截然不同，本发明的方法实质性地丰富了本领域。
以下描述有关A、B、C和D步骤的制备性实施例及解释说明。反应步骤A：通式II和III(其中Z1到Z5，R3和U如上所定义)的化合物在碱存在下方便地进行反应。特别适合的无机碱是碱金属或碱土金属化合物如锂、钠、钾、镁、钙、锶和钡的氢氧化物、氧化物或碳酸盐或氢化物如氢化钠、还有氧化物如ZnO、Al2O3、Ag2O等。
特别适合的有机碱包括NH3、烷基胺、二烷基胺、哌啶、喹啉、叔胺如三乙胺、三亚乙基二胺、哌啶、4-二甲氨基吡啶及烃氧基金属如NaOCH3、NaOEt、叔丁醇钾等。
虽非必需，但使用溶剂或稀释剂对反应有利。举例说明适合的溶剂和稀释剂：卤代烃，优选氯代烃如四氯乙烯、四氯乙烷、二氯丙烷、二氯甲烷、二氯丁烷、氯仿、四氯化碳、三氯乙烷、三氯乙烯、五氯乙烷、1，2-二氯乙烷、1，1-二氯乙烷、1，2-顺-二氯乙烯、氯苯、氟苯、溴苯、二氯苯、二溴苯、氯甲苯、三氯甲苯；醚类如：乙基丙基醚、甲基叔丁基醚、正丁基乙基醚、二正丁基醚、二异丁基醚、二异戊基醚、二异丙基醚、苯甲醚、环己基甲醚、乙醚、乙二醇二甲醚、四氢呋喃、二噁烷、硫代苯甲醚、二氯二乙基醚；硝化烃如硝基甲烷、硝基乙烷、硝基苯、氯代硝基苯、邻硝基甲苯；腈类如乙腈、丁腈、异丁腈、苯基腈、间氯苯基腈；脂肪、芳香或环脂烃如庚烷、己烷、辛烷、壬烷、繖花烃、沸点范围为70℃到190℃的石油馏份、苯、甲苯、环己烷、甲基环己烷、萘烷、石油醚、石油英、三甲基戊烷如2，3，3-三甲基戊烷；酯类如乙酸乙酯、乙酸异丁酯：酰胺类如甲酰胺、N-甲基甲酰胺、N-甲基吡咯烷酮、二甲基甲酰胺；酮类如丙酮、甲基乙基酮；二甲亚砜。上述溶剂和稀释剂的混合物也可以使用。
反应温度优选在从0℃到稀释剂沸点的范围内。
在A步反应中特别优选的碱为碱金属碳酸盐，最优选为碳酸钠或碳酸钾，优选稀释剂为乙腈，特别优选温度范围为60℃到65℃。
化合物IV的分离用已知方法完成，一般是蒸发去除稀释剂，残余物用乙酸乙酯回收，然后用碳酸钾水溶液洗涤有机提取层。用干燥剂如硫酸钠干燥后，将有机相蒸发浓缩。形成的式IV的异羟肟酸酯可以不经进一步纯化而用于下一步反应，这是本发明方法的一个重要优势。
式II和III的起始原料为已知化合物或可用已知方法来制备(如：Org、Synth、Coll、Vol.II，67和J.Am、Chem、Soc.31，3759(1966))。反应步骤B：
在反应步骤A中得到的式IV的粗品(其中Z1-Z5和R3如上所定义)皂化生成通式I(其中Z1、Z2、R3和Y如上所定义)的化合物的反应，在式HY(其中Y为酸的阴离子)的酸存在下，在优选为式R3OH的稀释剂(可进一步加入A中提到的溶剂)中进行，反应温度在0℃到稀释剂沸点，优选从20℃到稀释剂回流温度范围内。
适合的酸HY方便地为的氢卤酸(盐酸、氢溴酸或氢碘酸)、磺酸(取代或未取代的苯磺酸、甲磺酸、三氟甲磺酸)、羧酸(甲酸、乙酸、三氟乙酸)、高氯酸、四氟硼酸、磷酸、六氟磷酸、硫酸或亚硫酸。本反应并不意味着限制使用其它可能的酸。反应步骤C：
反应步骤B中得到的式I的盐可与式VII的酮(其中R1和R2如前述所定义)在反应步骤A中所定义的碱存在下，在惰性稀释剂如醚(如四氢呋喃或二噁烷或二甲氧基醚)、酯(如乙酸乙酯)、卤代烃(如1，2-二氯乙烷或氯仿或二氯甲烷)、酰胺(如二甲基甲酰胺或N-甲基吡咯烷酮)、芳香化合物(如苯或甲苯)、乙腈、二甲亚砜中反应。反应优选在同时作为稀释剂和碱的吡啶中进行。反应在0℃到稀释剂或碱的沸点温度范围内进行。优选温度范围为50℃到稀释剂回流温度。若反应在吡啶中进行，80℃到116℃的温度范围尤为优选。
通式V的产品用已知方法蒸去稀释剂、用水回收残物来分离和纯化。酸化、提取后，形成的粗产品用已知方法纯化，特别是蒸馏或色谱方法。产品以异构体混合物(E/Z)的形式得到。反应步骤D：
a)反应步骤C中得到的式V中间体的乙酸酯侧链可用一般方法转变为羟基丙烯酸酯侧链。此步骤包括用甲酸甲酯在强碱如醇钠(优选甲醇钠)或NaH、NaNH2、叔丁醇钾等存在下处理式V的中间体。特别适合的溶剂为极性溶剂如二甲基甲酰胺、醚(四氢呋喃、二噁烷等)、醇和叔丁醇或甲醇、及酮如叔丁基甲基酮。反应温度在-10℃到+60℃之间，优选从0℃到40℃。
接下来生成烷氧丙烯酸酯侧链的烷化反应可用碘代烷或叠氮甲烷方便地进行。适当地用硫酸二甲酯在碱性介质中以烷基氰化物为溶剂(优选乙腈)进行反应，得到甲氧丙烯酸酯。反应温度在0℃到+70℃之间。
b)反应步骤C中所得式V中间体的乙酸酯侧链可用亚硝酸酯在碱性介质中转化为肟基乙醛酸酯侧链，后者可用a)中描述的相同方法烷基化。亚硝酸烷基酯如亚硝酸乙酯、亚硝酸叔丁基酯、亚硝酸异戊基酯等在碱如NaOH、KOH、NaH、碱金属醇化物(如叔丁醇钾或NaOCH3)存在下适合用于引入肟基。反应温度在-10℃到+60℃之间，优选从0℃到40℃。可用极性惰性溶剂，特别是醚、醇和酮，优选a)中提及的那些种类。制备型实例实施例1(反应步骤A)
将102g(0.74mol)苯基异羟肟酸2、111g(0.8mol)粉状碳酸钾和1400ml乙腈的混合物加热到60℃。0.5小时后，60℃-65℃下0.5小时内滴加162g邻溴甲基苯基乙酸甲酯1(邻甲苯基乙酸甲酯用N-溴琥珀酰亚胺溴化所得68％的粗品)溶于100ml乙腈中的熔液，在此温度下搅拌反应混合液5.5小时。
为了纯化，将反应混合物冷却到25℃，用Hyflo Super Cel过滤，并在水喷射真空条件下蒸发浓缩。残余的油回收到1000ml乙酸乙酯中。用500ml6％的碳酸钾溶液洗涤后，分离各相，水相用300ml乙酯乙酯提取一次。合并有机相，用200ml水洗涤一次，用硫酸钠干燥，过滤并蒸发至干，生成182g桔黄色油状苯基异羟肟酸酯3。无需对此产品进一步纯化。实施例2(反应步骤B)
将182g实施例1中所得不纯的苯基异羟肟酸酯3和900ml8％的盐酸甲醇溶液加热到60℃。1小时后，除去过量甲醇，由胺盐酸盐4和苯甲酸甲酯组成的残余物与乙醚在35℃下搅拌0.5小时。将胺盐酸盐4粘性沉淀冷却至20℃，与醚溶液分离并在40℃-50℃下溶于500ml四氢呋喃中。将此液冷却并过滤，得到65.5g(
62％的理论产量，从溴化物1开始计算)的浅绿色细结晶粉末，熔点为157°-158℃(分解)。
反应步骤A和B的特色在于使用便宜易得的起始原料和辅助剂。与已有技术合成式VI化合物的方法相比，一个实质性优点在于使用邻甲苯基乙酸甲酯用N-溴琥珀酰亚胺(NBS)溴化得到的未经纯化的粗产品通过反应步骤A和B仍可能得到高产率(如60-70％)的4。与已有技术合成化合物VI的方法相比，第二个实质性优点在于得到化合物4使甚至用
这样的酮也可能得到相当产率的式VI化合物，而用这样的酮的肟按路线IIa)反应是根本不可能的或反应产率不令人满意。实施例3(反应步骤C)
20℃下向53.1g(0.282mol)3-三氟甲基苯乙酮6在530ml吡啶中的溶液中加入65.4g(0.282mol)胺盐酸盐4，加热反应混合物至90℃。在约2小时后反应结束，过量吡啶在水喷射真空下除去。残余物溶于600ml冷水中，用浓盐酸调pH至1-2。用乙酸乙酯萃取3次后，合并有机相，用水洗一次，再用10％碳酸钠溶液洗一次，用硫酸钠干燥，过滤并在水喷射真空下蒸发至干，生成101g黄色油(
98％理论值)，其中所含纯7为E/Z混合物(E：87％，Z：13％)(NMR光谱)。此肟也可以在高真空下蒸馏；b.p.168°-178℃/0.1mbar。实施例4：(反应步骤D)
在29℃-35℃下向6.7g(0.28mol)氢化钠在100ml叔丁基甲基醚中的悬浮液中加入0.5ml甲醇后，滴加46.0g(0.125mol)的肟醚7、31.3g(0.52mol)甲酸甲酯和150ml叔丁基甲基醚的混合液。开始时需要等待短暂的诱导阶段结束。滴加肟醚溶液计3小时。然后将反应混合物在30°-35℃下搅拌5小时。为了纯化，将反应混合物冷却至0℃-5℃，先滴加约2ml甲醇，再滴加100ml甲醇，用约20ml醋酸调pH至5，分离各相。水相用300ml叔丁基甲基醚提取两次。合并的有机相用5％的碳酸钠溶液洗涤两次、用硫酸钠干燥、过滤并蒸发至干，得到48.3g(
98.1％的理论值)黄色油9，NMR光谱表明它为纯品(E/Z混合物)。
25℃下，30分钟内向48.2g(0.122mol)的烯醇9、25.3g(0.183mol)的粉状碳酸钾在500ml乙腈中的溶液中滴加16.4g(0.13mol)硫酸二甲酯，然后在25℃下搅拌混合物5小时。为纯化，真空除去乙腈，残余物回收在500ml水和500ml甲苯中。分离各相，水相用200ml甲苯提取一次。合并后的有机相用水洗涤一次、真空蒸发至干，然后在60℃和0.13mbar下完全蒸干，得到48.0g(
96.5的理论值)桔黄色油10，NMR分析表明它含89％的E-反；8％的E-顺；及3％的Z异构体。实施例5：(反应步骤D)
30℃下1小时内向1.8g(15.6mmol)叔丁醇钾在15ml叔丁醇中的溶液中滴加含5.7g(15.6mmol)的肟醚7、6.0g(52.3mmol)的亚硝酸叔丁酯(90％)和10ml叔丁醇的溶液。然后在35℃下搅拌反应混合物2小时。为提纯，将反应混合物冷却至10℃，并滴加10ml水和1.2g醋酸。将混合物溶于200ml乙酸乙酯中，用水洗涤并在水喷射真空下蒸发至干，得到5.2g桔黄色油12。此油在25ml己烷中加热纯化，从中此产品开始结晶。将此液冷却至20℃、吸滤、熔点132°-138℃的淡黄色结晶产品在8ml甲苯和1ml己烷中重结晶得到2.4g(
39％)白色结晶粉末，熔点为141-144℃。
25℃下向2.3g(5.8mmol)所得肟12、1.6g(11.6mmol)碳酸钾和25ml乙腈的混合物中加入0.79g硫酸二甲酯。搅拌3小时后，水喷射真空下除去乙腈，残余物加入水中。用乙酸乙酯提取2次，合并有机相，用水洗涤、用硫酸钠干燥、过滤并蒸发浓缩。此二肟醚13在硅胶柱上用乙酸乙酯/己烷(1∶2)洗脱条件下层析分离，得到淡黄色结晶，熔点为67°-69℃。实施例6：(反应步骤C)
38.8g(1，4-苯并二噁烷-6-基)环丙基酮15和44.0g4在400ml吡啶中100℃下搅拌4小时。蒸馏除去溶剂，残余物在0.5升冰水和1升乙醚中搅拌。分出水相，有机相用水洗涤、用硫酸钠干燥并真空浓缩。残余物在硅胶上用二氯甲烷洗脱下进行层析，得到32g浅黄色油16，MS：381(M+，12％)，163(100)。实施例7：(反应步骤D)
将39.8g{〔α-(环丙基-3，4-亚乙基二氧基苄基)亚胺基〕氧基}-邻甲苯乙酸甲酯16在100ml二甲基甲酰胺(DMF)和62ml甲酸甲酯中的溶液慢慢滴加到8.0g氢化钠在300ml二甲基甲酰胺中的悬浮液中。将反应混合物室温搅拌3小时，用醋酸酸化，然后用乙醚提取。有机相用洗两次、用氯化钠溶液洗一次、硫酸钠干燥并真空浓缩，得到2-〔α-{〔(α-环丙基-3，4-亚乙基二氧基苄基)亚胺基〕氧基}-邻甲苯基〕-3-羟基-丙烯酸甲酯17粗品，它无需纯化进行下一步反应。
上述原料17与10.4ml硫酸二甲酯、15.2g碳酸钾及350ml丙酮一起室温搅拌2小时。将混合物过滤，将滤液真空浓缩，得到红棕色油。将此油在硅胶上用四氢呋喃/亚己烷(1∶2)进行层析，得到30g黄色油状2-〔α-｛〔(α-环丙基-3，4-亚乙基二氧基苄基)亚胺基〕氧基}-邻甲苯基〕-3-甲氧基丙烯酸〔E〕-甲酯。实施例8：(反应步骤C)制备
基本按照实施例6描述的步骤，50.0g(1，4-苯并二噁烷-6-基)三氟甲基酮与49.8g胺盐酸盐4在420ml吡啶中反应生成黄色油状酯19。实施例9：(反应步骤D)制备
基本按照实施例7中描述的步骤，将按实施例8得到的中间体19在甲酸甲酯中的溶液滴加到NaH在DMF中的悬浮液中，反应生成羟基丙烯酸甲酯，然后后者用硫酸二甲酯甲基化。在硅胶上用乙醚/正己烷(1∶1)进行层析，生成浅黄色油状3-甲氧基-2-〔α{〔(α-三氟甲基-3，4-亚乙基二氧基苄基)亚胺基〕氧基}-邻甲苯基〕丙烯酸甲酯20，MS：451(M+，4％)145(100)。实施例10：(反应步骤C)制备
基本上按照实施例6的步骤，从35.0g(3，4-亚甲二氧基苯基)三氟甲基酮和37.5g 4得到黄色油状酯21。实施例11：(反应步骤D)制备基本按照实施例7描述的步骤，中间体21与甲酸甲酯及NaH在DMF中反应，得到羟丙烯酸甲酯粗品，后者用硫酸二甲酯甲基化得到22。在硅胶上用乙醚/正己烷(1∶2)进行层析，得到黄色油状3-甲氧基-2-〔α{〔(α-三氟甲基-3，4-亚 甲 二氧基苄基)亚胺基〕氧基}-邻甲苯基〕丙烯酸甲酯，MS：437(M+，1％)，145(100)。实施例12：(反应步骤C)
基本按照实施例6描述的方法，从80.0g酮23和79.7g胺盐酸盐4得到酯24。实施例13：(反应步骤D)
将50.0g按实施例12所得酯24和24.0g亚硝酸异戊酯在100ml甲醇中的溶液慢慢滴加到34ml甲醇钠中(30％甲醇)。2小时后，按实施例5中描述的方法纯化。然后得到的肟25在丙酮中用硫酸二甲酯/碳酸钾甲基化。在硅胶上层析(乙醚/正己烷＝1∶9)并在乙醚/正己烷中重结晶后，得到无色结晶26。m.p.130-132℃。实施例14：(反应步骤C)制备
基本按照实施例6中描述的步骤，从58.0g3，4-二氟亚甲二氧基苯丙酮和62.7g 4反应得到黄色油状酯27。实施例15：(反应步骤D)制备
基本按照实施例13中描述的方法，27与亚硝酸异戊酯在甲醇钠存在下在甲醇中反应，生成相应的肟，后者进一步与硫酸二甲酯在K2CO3/丙酮存在下反应，生成二肟醚28。硅胶层析(乙酸乙酯/正己烷：1∶9)后所得化合物28结晶的熔点为m.p.52-55℃。实施例16：(反应步骤C)制备
基本按照实施例6描述的步骤，从70.9g胺盐酸盐4和46.0g5-氟-2，3-二氢-1-茚酮反应得到酯29。实施例17：(反应步骤D)制备
基本按照实施例13描述的步骤，中间体29与亚硝酸酯如亚硝酸叔丁酯反应，生成相应的肟，然后肟再甲基化。硅胶层析(二氯甲烷/正己烷＝1∶9)后得到无色结晶30，熔点为89-92℃。
Claims (21)
1.式I的2-氨氧亚甲基苯乙酸酯衍生物游离碱及与质子酸所成盐，
其中
Z1和Z2为氢、卤原子、羟基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1-C4卤代烷氧基、C1-C4烷基羰基、C1-C4烷氧羰基、苯氧基、硝基、氰基、Z和Z2与所连苯基一起为萘或氢化萘；R3为氢或C1-C12烷基。
2.根据权利要求1的化合物，其中R3为氢或C1-C4烷基。
3.根据权利要求1的化合物，其中R3为甲基。
4.制备式I化合物的方法，它包括第一步反应A，取代的邻甲苯乙酸酯II与苯甲酰羟胺III
在有或无稀释剂存在下反应，得到的苯甲酰化的2-氨氧亚甲基苯乙酸酯IV
在第二步反应B中用HY酸进行酸皂化，
在式II、III和IV中R3、Z1和Z2如为式I所定义，
Z3、Z4和Z5可相同或不同，为氢、直链或支链C1-C6烷基、卤原子、羟基、直链或支链C1-C6烷氧基、硝基、氰基、N(R5)2、SO2NH2、取代或未取代的苯氧基、CF3、巯基，两R5取代基可相同或不同，为氢和/或直链或支链C1-C6烷基，并且其中
Z3和Z4可处在连位并一起形成亚甲二氧桥，或与所连结苯环一起形成萘环，及其中
U为离核离去基团。
5.根据权利要求4的方法，其中两步反应均在稀释剂存在下进行。
6.根据权利要求4的方法，其中Z3、Z4和Z5相互独立，各自为氢、甲基和卤原子。
7.根据权利要求6的方法，其中Z3＝Z4＝Z5为氢。
8.根据权利要求4的方法，其中U为卤离子、苯磺酸根、甲苯磺酸根、甲磺酸根、三氟甲磺酸根或乙酸根。
9.根据权利要求4的方法，其中U为溴离子。
10.根据权利标4的方法，其中A步反应是在碱存在下完成的。
11.根据权利要求10的方法，其中碱为碳酸钠或碳酸钾。
12.根据权利要求5的方法，其中用于A步反应的稀释剂选自醚、酮、酰胺、烃、卤代烃、腈、二甲亚砜或酯。
13.根据权利要求12的方法，其中稀释剂为乙腈。
14.根据权利要求4的方法，其中A步反应中反应温度在0℃到稀释剂沸点范围内。
15.根据权利要求14的方法，其中反应温度在60℃到65℃之间。
16.根据权利要求4的方法，其中HY选自氢卤酸、磺酸、羧酸、高氯酸、四氟硼酸、磷酸、六氟磷酸、硫酸和亚硫酸。
17.根据权利要求16的方法，其中HY为盐酸或硫酸。
18.根据权利要求5的方法，其中用于B步反应的稀释剂为式R3-OH的醇，其中R3为C1-C12烷基。
19.根据权利要求4的方法，其中B步反应的反应温度在0℃到稀释剂沸点范围内。
20.根据权利要求19的方法，其中反应温度在20℃到稀释剂沸点范围内。
21.式I的化合物用于制备式VI的化合物的用途，
其中
X为CHO(C1-C4-烷基)、NO(C1-C4烷基)、未取代的CH2
R1和R2可相同或不同，为氢、氰基、直链或支链C1-C10烷基、C1-C4卤代烷基、C3-C6环烷基、C3-C6卤代环烷基、取代或未取代的芳基、取代或未取代的杂环基，
及R3、Z1和Z2如式I中所定义。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH3683/922 | 1992-12-01 | ||
| CH368392 | 1992-12-01 | ||
| CH3683/92-2 | 1992-12-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1093355A CN1093355A (zh) | 1994-10-12 |
| CN1049426C true CN1049426C (zh) | 2000-02-16 |
Family
ID=4261280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93121110A Expired - Fee Related CN1049426C (zh) | 1992-12-01 | 1993-11-30 | 苯乙酸衍生物及其制备方法和用途 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5606095A (zh) |
| EP (1) | EP0600835B1 (zh) |
| JP (1) | JPH06199759A (zh) |
| KR (1) | KR100309533B1 (zh) |
| CN (1) | CN1049426C (zh) |
| AT (1) | ATE142616T1 (zh) |
| CA (1) | CA2110192A1 (zh) |
| CZ (1) | CZ284439B6 (zh) |
| DE (1) | DE59303746D1 (zh) |
| DK (1) | DK0600835T3 (zh) |
| ES (1) | ES2092801T3 (zh) |
| GR (1) | GR3020989T3 (zh) |
| HU (1) | HU216444B (zh) |
| IL (1) | IL107790A (zh) |
| MX (1) | MX9307510A (zh) |
| TW (1) | TW279845B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100525757C (zh) * | 2003-06-20 | 2009-08-12 | 麦它波莱克斯股份有限公司 | α-(苯氧基)苯乙酸衍生物的拆分 |
| CN103214327A (zh) * | 2013-03-22 | 2013-07-24 | 郑州泰基鸿诺药物科技有限公司 | 一种芳香环或芳杂环三氟甲基酮化合物及其制备方法 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0840726T3 (da) * | 1995-06-28 | 2001-11-19 | Syngenta Ltd | Fremgangsmåde til fremstilling af 2-(6-substitueret pyrid-2-yloxymethyl)-phenylacetat |
| CN1787989A (zh) * | 2003-03-13 | 2006-06-14 | 小野药品工业株式会社 | 亚氨醚衍生化合物和含有该化合物作为活性成分的药物 |
| CA2932121A1 (en) * | 2007-11-30 | 2009-06-11 | Newlink Genetics Corporation | Ido inhibitors |
| CN103387490B (zh) | 2012-05-09 | 2015-08-26 | 中国科学院兰州化学物理研究所 | 一种甲苯羰化合成苯乙酸的方法 |
| CN111057109B (zh) * | 2019-12-09 | 2023-08-11 | 西安近代化学研究所 | 一种具有膦酸酯的苯并二恶茂衍生物及其应用 |
| US20230255200A1 (en) * | 2020-07-08 | 2023-08-17 | Basf Se | Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors vi |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0460575A1 (de) * | 1990-06-05 | 1991-12-11 | Ciba-Geigy Ag | Aromatische Verbindungen |
| EP0463488A1 (de) * | 1990-06-27 | 1992-01-02 | BASF Aktiengesellschaft | O-Benzyl-Oximether und diese Verbindungen enthaltende Pflanzenschutzmittel |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES271700A1 (es) * | 1960-11-03 | 1962-03-01 | Smith & Nephew | Un procedimiento de hacer un derivado de hidroxilamina |
| DE1276046B (de) * | 1964-07-17 | 1968-08-29 | Universal Oil Prod Co | Verfahren zur Herstellung von ª‡-substituierten N-Alkoxyaethylaminen |
| CA962696A (en) * | 1970-12-14 | 1975-02-11 | Gyogyszerkutato Intezet | Methoxy amine derivatives and process for preparing them |
| DE2532420A1 (de) * | 1975-07-19 | 1977-02-03 | Boehringer Mannheim Gmbh | Phenylessigsaeure-derivate und verfahren zu ihrer herstellung |
| GB8617648D0 (en) * | 1986-07-18 | 1986-08-28 | Ici Plc | Fungicides |
| ATE169616T1 (de) * | 1988-11-21 | 1998-08-15 | Zeneca Ltd | Zwischenverbindungen zur herstellung von fungiziden |
| GB9018408D0 (en) * | 1990-08-22 | 1990-10-03 | Ici Plc | Fungicides |
| NZ242290A (en) * | 1991-04-15 | 1994-12-22 | Zeneca Ltd | Pyridyl and pyrimidinyl substituted oxime-o-benzyl ether derivatives; preparatory processes, fungicidal compositions and an intermediate |
| CH686307A5 (de) * | 1991-04-19 | 1996-02-29 | Ciba Geigy Ag | Oximether des 3-Methoxy-2-(o-tolyl)acrylsouremethylesters, Verfahren zu ihrer Herstellung und fungizide Mittel, die diese als Wirkstoffe enthalten. |
-
1993
- 1993-11-16 TW TW082109564A patent/TW279845B/zh active
- 1993-11-23 DK DK93810809.9T patent/DK0600835T3/da active
- 1993-11-23 ES ES93810809T patent/ES2092801T3/es not_active Expired - Lifetime
- 1993-11-23 EP EP93810809A patent/EP0600835B1/de not_active Expired - Lifetime
- 1993-11-23 DE DE59303746T patent/DE59303746D1/de not_active Expired - Fee Related
- 1993-11-23 AT AT93810809T patent/ATE142616T1/de not_active IP Right Cessation
- 1993-11-26 KR KR1019930025581A patent/KR100309533B1/ko not_active IP Right Cessation
- 1993-11-29 CA CA002110192A patent/CA2110192A1/en not_active Abandoned
- 1993-11-29 CZ CZ932575A patent/CZ284439B6/cs not_active IP Right Cessation
- 1993-11-29 IL IL107790A patent/IL107790A/xx not_active IP Right Cessation
- 1993-11-30 HU HU9303395A patent/HU216444B/hu not_active IP Right Cessation
- 1993-11-30 MX MX9307510A patent/MX9307510A/es not_active IP Right Cessation
- 1993-11-30 CN CN93121110A patent/CN1049426C/zh not_active Expired - Fee Related
- 1993-12-01 JP JP5329966A patent/JPH06199759A/ja active Pending
-
1995
- 1995-06-05 US US08/462,259 patent/US5606095A/en not_active Expired - Fee Related
-
1996
- 1996-09-12 GR GR960402333T patent/GR3020989T3/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0460575A1 (de) * | 1990-06-05 | 1991-12-11 | Ciba-Geigy Ag | Aromatische Verbindungen |
| EP0463488A1 (de) * | 1990-06-27 | 1992-01-02 | BASF Aktiengesellschaft | O-Benzyl-Oximether und diese Verbindungen enthaltende Pflanzenschutzmittel |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100525757C (zh) * | 2003-06-20 | 2009-08-12 | 麦它波莱克斯股份有限公司 | α-(苯氧基)苯乙酸衍生物的拆分 |
| CN103214327A (zh) * | 2013-03-22 | 2013-07-24 | 郑州泰基鸿诺药物科技有限公司 | 一种芳香环或芳杂环三氟甲基酮化合物及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| HU216444B (hu) | 1999-06-28 |
| CZ284439B6 (cs) | 1998-11-11 |
| IL107790A0 (en) | 1994-02-27 |
| CA2110192A1 (en) | 1994-06-02 |
| DE59303746D1 (de) | 1996-10-17 |
| HU9303395D0 (en) | 1994-03-28 |
| ATE142616T1 (de) | 1996-09-15 |
| KR940014299A (ko) | 1994-07-18 |
| JPH06199759A (ja) | 1994-07-19 |
| GR3020989T3 (en) | 1996-12-31 |
| CN1093355A (zh) | 1994-10-12 |
| KR100309533B1 (ko) | 2002-04-06 |
| HUT69330A (en) | 1995-09-28 |
| US5606095A (en) | 1997-02-25 |
| TW279845B (zh) | 1996-07-01 |
| EP0600835A1 (de) | 1994-06-08 |
| IL107790A (en) | 1997-09-30 |
| EP0600835B1 (de) | 1996-09-11 |
| ES2092801T3 (es) | 1996-12-01 |
| DK0600835T3 (da) | 1996-09-30 |
| CZ257593A3 (en) | 1994-06-15 |
| MX9307510A (es) | 1994-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9174943B2 (en) | Processes for the synthesis of diarylthiohydantoin and diarylhydantoin compounds | |
| AU2006331365B2 (en) | Epoxide intermediate in the TAMIFLU synthesis | |
| CA3111466A1 (en) | Salts of methyl 6-(2,4-dichlorophenyl)-5-[4-[(3s)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7h-benzo[7]annulene-2-carboxylate and preparation process thereof | |
| EP0470310B1 (en) | Novel benzopyrans and process for their production | |
| US6946556B1 (en) | Preparation of opioid analgesics by a one-pot process | |
| CN1049426C (zh) | 苯乙酸衍生物及其制备方法和用途 | |
| IL298316A (en) | Process for preparing butyl-(5s)-5-({2-[4-(butoxycarbonyl)phenyl]ethyl}[2-(2-{[3-chloro-4'-(trifluoromethyl)[biphenyl]-4-yl) methoxy}phenyl)ethyl]amino)-8,7,6,5-tetrahydroquinoline-2-carboxylate | |
| KR101488740B1 (ko) | 새로운 키랄 중간체, 그 키랄 중간체의 제조방법 및 톨테로딘, 페소테로딘 또는 그 활성대사물질의 제조에서 그키랄 중간체의 사용 | |
| RU2470018C2 (ru) | Новые производные пирокатехина | |
| JP2002525349A (ja) | 新規６−（４−フエニルブトキシ）ヘキシルアミン誘導体およびサルメテロールの製法 | |
| CA2380854A1 (en) | A process for the preparation of venlafaxin | |
| ES2912409T3 (es) | Intermedios y procesos para la preparación de linagliptina y sus sales | |
| JP2002505317A (ja) | キラルβ−アミノ酸の合成 | |
| RU2810493C1 (ru) | Эффективный процесс получения производных 6-карбоксибензоксазола | |
| JP4255296B2 (ja) | 環状含フッ素アルコールの製造方法 | |
| JP4829418B2 (ja) | 光学活性なハロヒドリン誘導体およびその使用方法 | |
| CN1070647A (zh) | 制备具有光学活性的假蟾毒胺醇的方法 | |
| JP4218310B2 (ja) | 光学活性２−アミノ−２−フェニルエタノール類の製造方法およびその中間体 | |
| JP4329306B2 (ja) | ベンゾニトリル誘導体及びその製造方法 | |
| US20040122099A1 (en) | Process for preparing S-(2-aminoethyl)-2-methyl-L-cysteine | |
| CN117342978A (zh) | 一种胺的氰甲基化方法 | |
| CN116715618A (zh) | 地佐辛中间体杂质及其制备方法 | |
| JP4396025B2 (ja) | ４−メトキシメチル−２，３，５，６−テトラフルオロベンゼンメタノールの製造法 | |
| CA2433516A1 (en) | Processes for preparing chromanylbenzoic acids | |
| JP2958665B2 (ja) | 光学活性３，５−アンチ−ジヒドロキシカルボン酸エステル誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Applicant after: NOVARTIS AG Applicant before: Shibageji AG |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: CIBA-GEIGY AG TO: NOVANNIS COMPANY |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: BAYER AG Free format text: FORMER OWNER: SINGENTA PARTICIPATION AG Effective date: 20010807 Owner name: SINGENTA PARTICIPATION AG Free format text: FORMER OWNER: NOVANNIS COMPANY Effective date: 20010807 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20010807 Address after: The Federal Republic of Germany Leverkusen Patentee after: BAYER AG Address before: Basel, Switzerland Patentee before: SYNGENTA PARTICIPATIONS AG Effective date of registration: 20010807 Patentee after: SYNGENTA PARTICIPATIONS AG Patentee before: Novartis AG |
|
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |