CN1261875A - 2,4,5－三氟－苄腈的制备方法 - Google Patents
2,4,5－三氟－苄腈的制备方法 Download PDFInfo
- Publication number
- CN1261875A CN1261875A CN98806819A CN98806819A CN1261875A CN 1261875 A CN1261875 A CN 1261875A CN 98806819 A CN98806819 A CN 98806819A CN 98806819 A CN98806819 A CN 98806819A CN 1261875 A CN1261875 A CN 1261875A
- Authority
- CN
- China
- Prior art keywords
- thinner
- acid
- cyanide
- alkali metal
- fluoro
- 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.)
- Granted
Links
- DLKNOGQOOZFICZ-UHFFFAOYSA-N 2,4,5-trifluorobenzonitrile Chemical compound FC1=CC(F)=C(C#N)C=C1F DLKNOGQOOZFICZ-UHFFFAOYSA-N 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- -1 alkali metal cyanide Chemical class 0.000 claims abstract description 16
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 230000009935 nitrosation Effects 0.000 claims description 10
- 238000007034 nitrosation reaction Methods 0.000 claims description 10
- MGNPLIACIXIYJE-UHFFFAOYSA-N n-fluoroaniline Chemical compound FNC1=CC=CC=C1 MGNPLIACIXIYJE-UHFFFAOYSA-N 0.000 claims description 8
- 150000002736 metal compounds Chemical class 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 5
- VQTGUFBGYOIUFS-UHFFFAOYSA-N nitrosylsulfuric acid Chemical compound OS(=O)(=O)ON=O VQTGUFBGYOIUFS-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 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 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 239000005749 Copper compound Substances 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical group N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 150000001880 copper compounds Chemical class 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M nitrite group Chemical group N(=O)[O-] IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 abstract description 3
- QMYVWJVVVMIBMM-UHFFFAOYSA-N 2,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C=C1F QMYVWJVVVMIBMM-UHFFFAOYSA-N 0.000 abstract 1
- 150000003623 transition metal compounds Chemical class 0.000 abstract 1
- 239000000047 product Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012954 diazonium Substances 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- HWWYDZCSSYKIAD-UHFFFAOYSA-N 3,5-dimethylpyridine Chemical compound CC1=CN=CC(C)=C1 HWWYDZCSSYKIAD-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-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- DVTULTINXNWGJY-UHFFFAOYSA-N 1-Bromo-2,4,5-trifluorobenzene Chemical compound FC1=CC(F)=C(Br)C=C1F DVTULTINXNWGJY-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical class CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- NTSLROIKFLNUIJ-UHFFFAOYSA-N 5-Ethyl-2-methylpyridine Chemical compound CCC1=CC=C(C)N=C1 NTSLROIKFLNUIJ-UHFFFAOYSA-N 0.000 description 1
- KNCHDRLWPAKSII-UHFFFAOYSA-N 5-ethyl-2-methylpyridine Natural products CCC1=CC=NC(C)=C1 KNCHDRLWPAKSII-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-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
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 description 1
- SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
- VQWWKYLNRCKQRP-UHFFFAOYSA-N N[Ca] Chemical compound N[Ca] VQWWKYLNRCKQRP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- VBIIFPGSPJYLRR-UHFFFAOYSA-M Stearyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C VBIIFPGSPJYLRR-UHFFFAOYSA-M 0.000 description 1
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 1
- GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 150000007962 benzene acetonitriles Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
- 229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical group CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002897 organic nitrogen compounds Chemical class 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 239000004304 potassium nitrite Substances 0.000 description 1
- 235000010289 potassium nitrite Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical class [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YTWOHSWDLJUCRK-UHFFFAOYSA-N thiolane 1,1-dioxide Chemical compound O=S1(=O)CCCC1.O=S1(=O)CCCC1 YTWOHSWDLJUCRK-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及制备式(Ⅰ)所示的2,4,5－三氟—苄腈的方法,该方法包括下述步骤A)在稀释剂存在下,式(Ⅱ)所示的2,4,5－三氟－苯胺与亚硝基化剂反应;B)在过渡金属化合物、酸受体和稀释剂存在下,步骤A)的产物与碱金属氧化物反应。
Description
本发明涉及2，4，5-三氟-苄腈的制备方法，该化合物用作药物和农业领域活性化合物的原料。
已知，于170℃-190℃间，在封闭的反应容器中，1-溴-2，4，5-三氟苯和氰化铜(I)和N-甲基-吡咯烷酮加热数小时可得到2，4，5-三氟-苄腈(参见EP-A-191 185)。但是，这种合成方法得到高度污染的产物，该产物只有经柱色谱分离后才能达到令人满意的纯度。
根据一些改进的方法，用N，N-二甲基甲酰胺作为溶剂并在回流状态下延长加热时间，用氰化铜(I)可以将1-溴-2，4，5-三氟苯转变为2，4，5-三氟-苄腈(参见“药物化学会志”31(1988)，983-991)。但是，该申请没有描述纯2，4，5-三氟-苄腈的分离。
如果适当的话，在反应助剂，例如氟化铯和十八烷基-三甲基氯化铵的存在下，并在稀释剂，例如二甲基亚硫、四亚甲基砜(sulpholane)和甲苯的存在下，在高于150℃的温度下，2，4-二氯-5-氟-苄腈与氟化钾的反应也是已知的(参见EP-A-431 373、EP-A-433 124、EP-A-497 239、EP-A-635 486)。但是，此处，2，4，5-三氟-苄腈在大多数情况下与其它产物一起得到，且产率较低或中等。只有采用大量的相转移催化剂，尤其是四烷基卤化磷，才能以相当高的产率得到2，4，5-三氟-苄腈(参见EP-A-557 949)。
人们还知道在低温下，通过2，4-二氟-苄腈与氟反应可得到2，4，5-三氟-苄腈和其它氟化产物的混合物(参见EP-A-566 268)。
已经描述了通过相应的三卤代苯胺经重氮盐并与金属氰化物反应，可合成三卤代苄腈，但不是合成2，4，5-三氟-苄腈(“SandmeyerProcess”，参见GB-A-951 770，Coll.Czech.Chem.Com.42(1977)，2001-2017)。但是，产物的质量和/或产率均不令人满意。
本发明的目的是提供一种以高纯度和高产率，从2，4，5-三氟-苯胺制备2，4，5-三氟-苄腈的方法。
本发明的目的可以通过制备式(I)所示的2，4，5-三氟-苄腈的方法实现。
其中，在第一步A)中，在稀释剂存在下，式(II)所示的2，4，5-三氟-苯胺
与亚硝基化剂反应；在第二步B)中，在过渡金属化合物、酸受体和稀释剂存在下，将步骤A)得到的反应产物与碱金属氰化物反应。
令人惊讶的是，通过本发明的方法，可以高产率和高纯度得到2，4，5-三氟-苄腈。
当根据本发明进行反应时，反应温度可在相当宽的范围内变化。通常，第一步在-20℃～+30℃下进行，优选-10℃～+20℃；第二步通常在-10℃～+40℃下进行，优选在0℃～+30℃。
本发明的两个步骤通常在大气压下进行。但是，本发明方法也可以在减压或加压下进行—通常压力为0.1巴～10巴。
原料2，4，5-三氟-苯胺是已知的，并可以简单的方式制备(参见GB-A-11 31 501、EP-A-415 585)。
本发明方法中的第一步在亚硝基化剂下进行。合适的亚硝基化剂为常用于制备重氮盐的亚硝基化剂。这些例子是：亚硝酸碱金属盐，例如亚硝酸钠和亚硝酸钾(在酸如硫酸、甲磺酸、甲酸或乙酸的存在下)；亚硝酸烷基酯(alkyl nitrite)，如亚硝酸甲基、乙基、正或异丙基、正、异、仲或叔丁基、正、异、仲或叔戊基酯，也可为亚硝酰基硫酸。
本发明方法第一步中特别优选的亚硝基化剂为亚硝酰基硫酸。
本发明方法的第二步在碱金属氰化物下进行。优选的碱金属氰化物为氰化钠或氰化钾。此外，可用过渡金属化合物，优选铜化合物，例如氰化铜或硫酸铜。令人惊讶的是过渡金属化合物的用量大大低于化学计算量，即以催化量使用。
本发明方法的第二步还可在酸受体的存在下进行。合适的酸受体为常用的无机碱或有机碱或酸粘合剂。优选包括碱金属或碱土金属的乙酸盐，氨化物，碳酸盐，碳酸氢盐，氢化物，氢氧化物或醇盐，例如乙酸钠，乙酸钾或乙酸钙；氨基锂，氨基钠，氨基钾或氨基钙；碳酸钠，碳酸钾或碳酸钙；碳酸氢钠，碳酸氢钾或碳酸氢钙；氢化锂，氢化钠，氢化钾或氢化钙；氢氧化锂，氢氧化钠，氢氧化钾或氢氧化钙；甲醇钠，乙醇钠，正或异丙醇钠，正、异、仲或叔丁醇钠或甲醇钾，乙醇钾，正或异丙醇钾，正、异、仲或叔丁醇钾；也可为碱性有机氮化合物，如三甲胺，三乙胺，三丙胺，三丁胺，乙基二异丙胺，N，N-二甲基环己胺，二环己胺，乙基-二环己胺，N，N-二甲基苯胺，N，N-二甲基苯甲胺，吡啶，2-甲基-、3-甲基-、4-甲基-、2，4-二甲基-、2，6-二甲基-、3，4-二甲基-和3，5-二甲基吡啶，5-乙基-2-甲基-吡啶，4-二甲基氨基-吡啶，N-甲基-哌啶，1，4-二氮杂二环[2.2.2]-辛烷(DABCO)，1，5-二氮杂二环[4.3.0]-壬-5-烯(DBN)或1，8-二氮二环[5.4.0]-十一碳-7-烯(DBU)。
优选使用碱金属的碳酸盐或碳酸氢盐，或碱土金属的碳酸盐或碳酸氢盐，例如碳酸(氢)钠或碳酸(氢)钾。
本发明的反应在稀释剂存在下进行。特别适于进行本发明方法的稀释剂为惰性有机溶剂。尤其包括脂族、脂环族或芳香族烃，优选卤代烃，如轻质汽油、苯、甲苯、二甲苯、氯苯、二氯苯、石油醚、己烷、环己烷、二氯甲烷、氯仿、四氯化碳；醚，例如乙醚、二异丙醚、二恶烷、四氢呋喃或乙二醇二甲醚或乙二醇二乙醚；酮，例如丙酮、丁酮或甲基异丁酮；羧酸，例如甲酸、乙酸或丙酸；腈，如乙腈、丙腈或丁腈；酰胺，如N，N-二甲基甲酰胺、N，N-二甲基乙酰胺、N-甲基-甲酰苯胺、N-甲基-吡咯烷酮或六甲基磷酸三胺；酯，如乙酸甲酯或乙酸乙酯；亚砜，如二甲基亚砜；醇，如甲醇、乙醇、正或异丙醇、乙二醇单甲醚、乙二醇单乙醚、二甘醇单甲醚、二甘醇单乙醚，及其与水或纯水的混合物。
特别优选进行本发明第一步的稀释剂为羧酸。进行本发明第二步时，优选用水作为另外的溶剂。
进行本发明第一步反应时，每摩尔式(II)所示的2，4，5-三氟-苯胺通常使用0.9～1.2mol，优选1.0～1.1mol的亚硝基化剂。
在本发明第一步的反应的优选的实施方案中，首先，式(II)所示的2，4，5-三氟-苯胺用合适的稀释剂稀释，再在搅拌下慢慢地计量加入亚硝基化剂。然后搅拌反应混合物直至第一步反应实际上进行完全。
进行本发明第二步的反应时，每摩尔步骤1使用的式(II)所示的2，4，5-三氟-苯胺通常使用1～10mol，优选2～8mol的碱金属氰化物和0.01～0.5mol，优选0.05～0.2mol的过渡金属化合物。
在本发明第二步反应的优选实施方案中，在搅拌下，向第一步得到的反应混合物中加入碱金属氰化物和过渡金属化合物的水溶液，并通过同时加入酸受体，保持pH或多或少地在中性范围内。然后搅拌反应混合物直至反应实际上进行完全。
在进行第二步反应之前，优选不分离第一步得到的反应产物。
可以常规方式处理和分离式(I)的反应产物。例如，反应混合物与不溶于水的有机溶剂-如乙酸乙酯-一起振荡，然后在减压下，从有机萃取液中小心地蒸馏出溶剂，剩下式(I)产物为残余物。
根据本发明方法制备的式(I)所示的2，4，5-三氟-苄腈可作为药物和农业领域中制备活性化合物的中间体(参见EP-A-191 185、EP-A-597 360、EP-A-617 026、EP-A-654 468)。
制备实施例：
实施例1
将4.4克(30mmol)的2，4，5-三氟-苯胺溶解在25ml乙酸中(“冰醋酸”)，用冰浴冷却。然后，搅拌下加入4.5克(31.5mmol)亚硝酰基硫酸，除去冰浴，继续搅拌反应混合物一小时(第一步)。
搅拌下，将得到的重氮盐溶液加入到冷却至5℃的7.8克(160mmol)氰化钠和0.3克(3mmol)氰化铜(I)的40ml水溶液中。连续加入约80ml 25％浓度的碳酸钠水溶液，保持pH值约在中性范围内。然后，反应混合物继续搅拌约15分钟，并分别用100ml乙酸乙酯萃取两次。在水泵产生的真空下，从合并的有机萃取液中小心地蒸馏出溶剂。
从而得到4.1克油状残余物2，4，5-三氟-苄腈(根据气相色谱分析，产物纯度为92％纯度，即理论的80％)。
Claims (10)
1. 2，4，5-三氟-苄腈的制备方法，其特征在于包括下述步骤：
A)在稀释剂存在下，2，4，5-三氟-苯胺与亚硝基化剂反应；
B)在过渡金属化合物、酸受体和稀释剂存在下，步骤A)得到的反应产物与碱金属氰化物反应。
2.如权利要求1所述的方法，其特征在于步骤A)在-20℃～+30℃下进行，优选-10℃～+20℃；步骤B)在-10℃～+40℃下进行，优选0℃～+30℃。
3.如权利要求1或2所述的方法，其特征在于所用的亚硝基化剂为亚硝酸碱金属盐、亚硝酸烷基酯和/或亚硝酰基硫酸。
4.如权利要求3所述的方法，其特征在于所用的亚硝基化剂为亚硝酰基硫酸。
5.如权利要求1～4所述的任一方法，其特征在于所用的碱金属氰化物为氰化钠和/或氰化钾。
6.如权利要求1～5所述的任一方法，其特征在于所用的过渡金属化合物为铜化合物，优选氰化铜和/或硫酸铜。
7.如权利要求1～6所述的任一方法，其特征在于所用的酸受体为碱金属碳酸盐，和/或碱土金属碳酸盐，和/或碱金属碳酸氢盐，和/或碱土金属碳酸氢盐，优选碳酸(氢)钠和/或碳酸(氢)钾。
8.如权利要求1～7所述的任一方法，其特征在于使用一种或多种惰性有机溶剂作为稀释剂。
9.如权利要求8所述的方法，其特征在于步骤A)中所用的稀释剂为羧酸，步骤B)中稀释剂为另外加入的水。
10.如权利要求1～9所述的任一方法，其特征在于在步骤B)之前步骤A)得到的反应产物不分离。
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| DE19727890.6 | 1997-07-01 | ||
| DE19727890A DE19727890A1 (de) | 1997-07-01 | 1997-07-01 | Verfahren zur Herstellung von 2,4,5-Trifluor-benzonitril |
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| CN1261875A true CN1261875A (zh) | 2000-08-02 |
| CN1144780C CN1144780C (zh) | 2004-04-07 |
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| JP (1) | JP2002507218A (zh) |
| CN (1) | CN1144780C (zh) |
| AU (1) | AU8216798A (zh) |
| BR (1) | BR9810647A (zh) |
| DE (2) | DE19727890A1 (zh) |
| DK (1) | DK0994849T3 (zh) |
| ES (1) | ES2179517T3 (zh) |
| HK (1) | HK1029577A1 (zh) |
| IL (1) | IL133130A (zh) |
| WO (1) | WO1999001425A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115551823A (zh) * | 2020-03-12 | 2022-12-30 | 阿尔第实业有限公司 | 1-溴-2,4,5-三氟苯的制备方法 |
| CN117466729A (zh) * | 2023-12-28 | 2024-01-30 | 山东国邦药业有限公司 | 一种2,4,5-三氟苯乙酸的合成方法 |
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| US2044015A (en) * | 1936-06-16 | Benzonitriles and process for | ||
| BE590258A (zh) | 1959-04-28 | |||
| GB1131501A (en) | 1965-05-24 | 1968-10-23 | Imp Smelting Corp Ltd | Fluorinated quinolines |
| EP0191185B1 (en) | 1984-12-14 | 1990-03-07 | Daiichi Seiyaku Co., Ltd. | Quinoline-carboxylic acid derivatives |
| FR2632648A1 (fr) | 1988-06-14 | 1989-12-15 | Thomson Csf | Polymeres mesomorphes a chaines laterales a forte anisotropie dielectrique utilisables en optique non lineaire |
| DE4238125A1 (de) | 1992-11-12 | 1994-05-19 | Bayer Ag | Substituierte Triazolinone |
| GB8919678D0 (en) | 1989-08-31 | 1989-10-11 | Ici Plc | Fluorobenzene derivatives |
| FR2655648B1 (fr) | 1989-12-11 | 1992-03-13 | Isochem Sa | Dichloro-2,4-fluoro-5-benzonitrile et procedes pour sa preparation, son application a la preparation de l'acide chloro-2-difluoro-4,5-benzouique et nouveau procede de preparation. |
| CH680056A5 (zh) | 1989-12-11 | 1992-06-15 | Bruderer Ag | |
| EP0497239A1 (de) | 1991-01-30 | 1992-08-05 | Hoechst Aktiengesellschaft | 2-Chlor-4,5-difluorbenzonitril und Verfahren zu seiner Herstellung |
| ES2125919T3 (es) | 1992-02-26 | 1999-03-16 | Clariant Gmbh | Procedimiento para la preparacion de 2,4,5-trifluoro-benzonitrilo. |
| GB9208123D0 (en) | 1992-04-13 | 1992-05-27 | Ici Plc | Substituted fluorobenzenes |
| GB9223195D0 (en) * | 1992-11-05 | 1992-12-16 | Octel Chem Ltd | Preparation of substituted aryl compounds |
| DE4309966A1 (de) | 1993-03-26 | 1994-09-29 | Bayer Ag | Substituierte 1-Aryltriazolinone |
| DE59407426D1 (de) | 1993-07-21 | 1999-01-21 | Clariant Gmbh | Verfahren zur Herstellung von Fluorbenzonitrilen |
| DE4339863A1 (de) | 1993-11-23 | 1995-05-24 | Bayer Ag | Substituierte Carbamoyltriazole |
| DE4416329A1 (de) * | 1994-05-09 | 1995-11-16 | Hoechst Ag | Substituierte 2-Chlor-3,4,5-trifluorbenzole und ein Verfahren zu ihrer Herstellung |
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- 1998-06-18 DK DK98932174T patent/DK0994849T3/da active
- 1998-06-18 US US09/446,491 patent/US6399807B1/en not_active Expired - Fee Related
- 1998-06-18 ES ES98932174T patent/ES2179517T3/es not_active Expired - Lifetime
- 1998-06-18 DE DE59805434T patent/DE59805434D1/de not_active Expired - Fee Related
- 1998-06-18 AU AU82167/98A patent/AU8216798A/en not_active Abandoned
- 1998-06-18 EP EP98932174A patent/EP0994849B1/de not_active Expired - Lifetime
- 1998-06-18 CN CNB988068192A patent/CN1144780C/zh not_active Expired - Fee Related
- 1998-06-18 WO PCT/EP1998/003732 patent/WO1999001425A1/de active IP Right Grant
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115551823A (zh) * | 2020-03-12 | 2022-12-30 | 阿尔第实业有限公司 | 1-溴-2,4,5-三氟苯的制备方法 |
| CN117466729A (zh) * | 2023-12-28 | 2024-01-30 | 山东国邦药业有限公司 | 一种2,4,5-三氟苯乙酸的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999001425A1 (de) | 1999-01-14 |
| DK0994849T3 (da) | 2002-11-25 |
| CN1144780C (zh) | 2004-04-07 |
| BR9810647A (pt) | 2000-08-01 |
| US6399807B1 (en) | 2002-06-04 |
| AU8216798A (en) | 1999-01-25 |
| ES2179517T3 (es) | 2003-01-16 |
| HK1029577A1 (en) | 2001-04-06 |
| IL133130A (en) | 2004-06-20 |
| DE19727890A1 (de) | 1999-01-07 |
| EP0994849B1 (de) | 2002-09-04 |
| DE59805434D1 (de) | 2002-10-10 |
| JP2002507218A (ja) | 2002-03-05 |
| EP0994849A1 (de) | 2000-04-26 |
| IL133130A0 (en) | 2001-03-19 |
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