TWI409252B - 製備烷基二鹵乙醯醋酸酯之方法 - Google Patents
製備烷基二鹵乙醯醋酸酯之方法 Download PDFInfo
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- TWI409252B TWI409252B TW097103839A TW97103839A TWI409252B TW I409252 B TWI409252 B TW I409252B TW 097103839 A TW097103839 A TW 097103839A TW 97103839 A TW97103839 A TW 97103839A TW I409252 B TWI409252 B TW I409252B
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- ethyl
- alkyl
- fluorine
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- 125000000217 alkyl group Chemical group 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 27
- 239000011737 fluorine Substances 0.000 claims description 27
- -1 1,1,2-trifluoro-2-(trifluoromethyl)ethyl-N,N-dimethylamine 1,1,2-Trifluoro-2-(trifluoromethyl)ethyl-N,N-diethylamine Chemical compound 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
- 239000000460 chlorine Chemical group 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000002585 base Substances 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Chemical group 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
- VIRGYRZBWQFJGJ-UHFFFAOYSA-N 1,1,2,2-tetrafluoro-n,n-dimethylethanamine Chemical compound CN(C)C(F)(F)C(F)F VIRGYRZBWQFJGJ-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 claims description 3
- SWADNLFRTHBCLE-UHFFFAOYSA-N n,n-diethyl-1,1,2,2-tetrafluoroethanamine Chemical compound CCN(CC)C(F)(F)C(F)F SWADNLFRTHBCLE-UHFFFAOYSA-N 0.000 claims description 3
- BNTFCVMJHBNJAR-UHFFFAOYSA-N n,n-diethyl-1,1,2,3,3,3-hexafluoropropan-1-amine Chemical compound CCN(CC)C(F)(F)C(F)C(F)(F)F BNTFCVMJHBNJAR-UHFFFAOYSA-N 0.000 claims description 3
- JLIDRDJNLAWIKT-UHFFFAOYSA-N 1,2-dimethyl-3h-benzo[e]indole Chemical compound C1=CC=CC2=C(C(=C(C)N3)C)C3=CC=C21 JLIDRDJNLAWIKT-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- DULCUDSUACXJJC-UHFFFAOYSA-N benzeneacetic acid ethyl ester Natural products CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 claims description 2
- VCYZVXRKYPKDQB-UHFFFAOYSA-N ethyl 2-fluoroacetate Chemical compound CCOC(=O)CF VCYZVXRKYPKDQB-UHFFFAOYSA-N 0.000 claims description 2
- 150000004795 grignard reagents Chemical class 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- BDZHKUAKSMWSAJ-UHFFFAOYSA-N 2-chloro-n,n-diethyl-1,1,2-trifluoroethanamine Chemical compound CCN(CC)C(F)(F)C(F)Cl BDZHKUAKSMWSAJ-UHFFFAOYSA-N 0.000 claims 1
- 235000019439 ethyl acetate Nutrition 0.000 abstract 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- 238000002360 preparation method Methods 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- IUEWOPMXNADAEB-UHFFFAOYSA-N 2,2-difluoro-n,n-dimethylacetamide Chemical compound CN(C)C(=O)C(F)F IUEWOPMXNADAEB-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- XUPYJHCZDLZNFP-UHFFFAOYSA-N butyl butanoate Chemical compound CCCCOC(=O)CCC XUPYJHCZDLZNFP-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- GZKHDVAKKLTJPO-UHFFFAOYSA-N ethyl 2,2-difluoroacetate Chemical compound CCOC(=O)C(F)F GZKHDVAKKLTJPO-UHFFFAOYSA-N 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- DLDBAVFXKUQZOE-UHFFFAOYSA-N 1,1,2,3,3,3-hexafluoro-n,n-dimethylpropan-1-amine Chemical compound CN(C)C(F)(F)C(F)C(F)(F)F DLDBAVFXKUQZOE-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WXCWKEDRTOVBMT-UHFFFAOYSA-N 1,1-dichloro-2,2-difluoro-n,n-dimethylethanamine Chemical compound CN(C)C(Cl)(Cl)C(F)F WXCWKEDRTOVBMT-UHFFFAOYSA-N 0.000 description 1
- SSUJUUNLZQVZMO-UHFFFAOYSA-N 1,2,3,4,8,9,10,10a-octahydropyrimido[1,2-a]azepine Chemical compound C1CCC=CN2CCCNC21 SSUJUUNLZQVZMO-UHFFFAOYSA-N 0.000 description 1
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-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
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 description 1
- OOJZGFFJNPGACA-UHFFFAOYSA-N 2-chloro-1,1,2-trifluoro-n,n-dimethylethanamine Chemical compound CN(C)C(F)(F)C(F)Cl OOJZGFFJNPGACA-UHFFFAOYSA-N 0.000 description 1
- XSJVWZAETSBXKU-UHFFFAOYSA-N 2-ethoxypropane Chemical compound CCOC(C)C XSJVWZAETSBXKU-UHFFFAOYSA-N 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 238000003434 Perkow synthesis reaction Methods 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZEXBOHFMOMKHQA-UHFFFAOYSA-N acetic acid 2,2-difluoroacetic acid Chemical compound FC(C(=O)O)F.C(C)(=O)O ZEXBOHFMOMKHQA-UHFFFAOYSA-N 0.000 description 1
- XBMGHVJWJAIHKS-UHFFFAOYSA-N acetic acid ethyl 2,2,2-trifluoroacetate Chemical compound C(C)(=O)O.FC(C(=O)OCC)(F)F XBMGHVJWJAIHKS-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000004812 organic fluorine compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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)
Description
本發明係關於一種藉使式(III)之α,α－二鹵胺與式(II)之羧酸酯於鹼的存在下反應以製備式(I)之烷基二鹵乙醯醋酸酯之方法。
烷基二氟乙醯醋酸酯係製備活性農業化學成分，特別係用於製備吡唑基羧醯苯胺之重要合成單位。
Tetrahedron 2001,57,2689－2700揭示4,4－二氟乙醯醋酸酯可藉使二氟乙醯醋乙酸酯與醋酸乙酯在氫化鈉(NaH)的存在下反應獲得。此反應25%之產率係令人極不滿意。此外，Tetrahedron 1996,52,119－130陳述4,4－二氟乙醯醋酸酯可藉使二氟醋酸乙酯與溴醋酸乙酯在Zn的存在下反應製得。
WO－A－2005/003077教導一種藉以三烷氧基膦(P(OAlk)3
)還原氯原子(其亦為已知的Perkow反應)由氯二氟乙醯醋酸酯進行烷基二氟乙醯醋酸酯之製備的三階段方法。
WO－A－2006/005612教導一種藉使2,2－二氟－N,N－二烷基乙醯胺與醋酸酯在鹼的存在下反應以製備4,4－二氟－3－側氧基丁酸酯之方法。如JACS,73,3684(1951)所述般，該烷基4,4－二氟－3－側氧基丁酸酯接著與三甲基原甲酸酯及醋酸酐反應以獲得乙基(2－乙氧基亞甲基)－4,4－二氟甲基乙醯醋酸酯，根據US－A－5,489,624，其可利用甲基肼轉化成乙基3－二氟甲基－1－甲基－4－吡唑羧酸酯。首先，所述路徑包括多個
反應步驟，其次，所用之2,2－二氟－N,N－二烷基乙醯胺非市售產品並僅可藉由氟化2,2－二氯－N,N－二烷基乙醯胺以近70%之小產率獲得。
先前技術中早已描述過之方法具有下列缺點：所用之二氟羰基鹵化物、鹵烷基羧酸酐及鹵丙烯酸酯係昂貴的、引發腐蝕問題及/或僅可以高度技術複雜性進行純化。
因此，本發明目的係提供一種較簡單並更經濟可行之製備烷基二鹵乙醯醋酸酯的方法。
令人驚訝地，該目的係藉由－種製備式(I)之烷基二鹵乙醯醋酸酯之方法達到，
其中X係氟、氯或CF3
，X’係氟、氯或溴，R1
係選自H、C1－12
－烷基、C5－18
－芳基、氯、溴及氟，且R3
獨立於R1
係選自C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，其係藉使式(III)之α,α－二鹵胺
其中R4
係選自C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，R5
獨立於R4
係選自C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，
與式(II)之羧酸酯其中R2
係選自氫、C1－12
－烷基、C5－18
－芳基、氯、溴及氟)反應。
在一本發明之較佳具體實施例中，X係選自氟、氯或CF3
；X’係選自氟或氯；R1
係選自C1－4
－烷基；.R2
獨立於R1
係選自C1－4
－烷基；R3
獨立於R1
係選自C1－4
－烷基；R4
係選自C1－4
－烷基；R5
獨立於R4
係選自C1－4
－烷基。
在一本發明之特佳具體實施例中，X係選自氟或氯；X’係氟；R1
係選自氫或氟；R2
係氫；R3
係選自甲基或乙基；R4
係選自甲基或乙基；R5
係選自甲基或乙基。
本發明之其他具體實施例可採自所附申請專利範圍及描述。
根據本發明方法可藉由7列流程(I)說明：
與本發明有關之術語「鹵素」(X)涵蓋彼等選自由氟、氯、溴及碘組成之群之元素，較佳係利用氟、氯及溴，特
佳係利用氟及氯。
視情況經取代基團可為經單－或多取代且該等取代基在多取代之情況下可為相同或不同的。
除非另外定義，與本發明有關之烷基係直鏈、分枝鏈或環狀烴基，其可視情況具有一、二或多個單或雙不飽和度或一、二或多個選自由O、N、P及S之雜原子。而且，本發明烷基可視情況經選自以下各者之其他基團取代：－X、－OR’、－SR’、－NR’2
、－SiR’3
、－COOR’、－CN及－CONR2
’基，其中R’可為氫或C1－4
－烷基。
「C1－12
－烷基」之定義涵蓋本文針對烷基所定義之最寬範圍。此定義特別涵蓋(例如)甲基、乙基、正丙基、異丙基、正丁基、異丁基、第二丁基及第三丁基、正戊基、正己基、1,3－二甲基丁基、3,3－二甲基丁基、正庚基、正壬基、正癸基、正十一基、正十二基之意義。
除非另外定義，與本發明有關之芳基係可具有一、二或多個選自O、N、P及S之雜原子並可視情況經選自以下各者之其他基團取代之芳族烴基：－X、－OR’、－SR’、－NR’2
、－SiR’3
、－COOR’、－CN及－CONR2
’基，其中R’可為氫或C1－4
－烷基。
「C5－18
－芳基」之定義涵蓋本文所定義具有5至18個骨架碳原子之芳基之最寬範圍。此定義特別涵蓋(例如)環戊烯基、苯基、環庚三烯基、環辛四烯基、萘基及蒽基之意義。
除非另外定義，與本發明有關之芳基烷基係可具有一、二或多個選自O、N、P及S之雜原子並具有至少一個C1－8
烷基側鏈之環狀芳族烴基，其中該側鏈可視情況與另一側鏈形成四－、五－或六－員環並可視情況經選自以下各者之其他基團取代：－X、－OR’、－SR’、－NR’2
、－SiR’3
、－COOR’、－CN及－CONR2
’基，其中R’可為氫或C1－4
－烷基。
「C7－19
－芳基烷基」之定義涵蓋本文所定義骨架及側鏈中共具有7至19個碳原子之芳基烷基之最寬範圍。此定義特別涵蓋(例如)甲苯基、鄰－二甲苯基、間－二甲苯基、對－二甲苯基及乙基苯基之意義。
本發明化合物視情況可以不同可能異構物形式，特別係立體異構物，例如E及Z、蘇及赤以及光學異構物，但若適合以及互變異構物之混合物形式存在。主張E及Z異構物，以及蘇及赤異構物，以及光學異構物、這些異構物之任何混合物及可能互變異構物形式。
在該等酯中，R2
及R3
基係各獨立地選自H、C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，較佳係選自C2－8
－烷基，更佳係選自C3－6
－烷基。
適合的羧酸酯之實例係醋酸甲酯、醋酸乙酯、氟醋酸乙酯、溴醋酸乙酯、丙酸乙酯、苯基醋酸乙酯、苯甲酸乙酯。
根據本發明，較佳係醋酸酯，特佳係醋酸乙酯。
根據本發明所用之α,α－二鹵胺係通式(III)之化合物
其中R4
係選自C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，較佳係選自C2－8
－烷基，更佳係選自C3－6
－烷基；R5
獨立於R4
係選自C1－12
－烷基、C5－18
－芳基或C7－19
－芳基烷基，較佳係選自C2－8
－烷基，更佳係選自C3－6
－烷基；X係CF3
、氟或氯，較佳係氟，且X’係氟、氯或溴，較佳係氟。
該等化合物可根據Petrov等人於Journal of Fluorine Chemistry 109(2001)25－31及Dmowski等人在Chemistry of Organic Fluorine Compounds II,A Critical Review,ACS,Washington DC(1995)263藉由經氟化/經鹵化烯與二級胺反應獲得並係(例如)由DuPont商業販售的。
根據本發明偏好使用之α-鹵胺係(例如)選自由1,1,2,2-四氟乙基-N,N-二甲基胺、1,1,2,2-四氟乙基-N,N-二乙基胺、1,1,2-三氟-2-(三氟甲基)乙基-N,N-二甲基胺、1,1,2-三氟-2-(三氟甲基)乙基-N,N-二乙基胺(Ishikawa試劑)、1,1,2-三氟-2-氯乙基-N,N-二甲基胺及1,1,2-三氟-2-氯乙基-N,N-二乙基胺(Yarovenko試劑)組成之群，較佳係1,1,2,2-四氟乙基-N,N-二甲基胺及1,1,2,2-四氟乙基-N,N-二乙基胺，特佳係1,1,2,2-四氟乙基-N,N-二甲基胺。
可製備氯胺或其鹽(類似Vilsmeier複合物)形式，例如N,N-二甲基二氟乙醯胺及(例如)草醯基氯、光氣或POCl3
：
式(III)之α,α-二鹵胺典型地與式(II)之羧酸酯在鹼的存在下反應，其將羧酸酯中羰基之α-位置去質子化。
根據本發明，適合的鹼係所有彼等具有鹼性以使該羧酸酯去質子化者。實例包括鹼金屬氫氧化物，例如氫氧化鋰、氫氧化鈉或氫氧化鉀，鹼金屬烷氧化物，例如
NaOMe、NaOEt、NaOt－Bu、KOt－Bu、氫化物，例如NaH、KH、烷基鋰試劑，例如n－BuLi或t－BuLi、LiN(iPr)2
、Grignard試劑，例如CH3
MgCl；磷氮烯及1,8－二氮雜雙環[5.4.0]十一烯(DBU)。
α,α－二鹵胺典型係在－50至60℃，較佳係－20至40℃，更佳係－10至30℃之溫度下與該等羧酸酯反應。
該反應可在較低壓力下、在標準壓力或在高壓下，較佳係在標準壓力下進行。
該反應可整批或在溶劑中進行。較佳係在一溶劑中進行反應。適合溶劑係(例如)選自由下列各者組成之群：脂族及芳族烴，例如正己烷、苯或甲苯，其可經氟及氯原子取代，例如二氯甲烷、二氯乙烷、氟苯、氯苯或二氯苯；醚，例如二乙基醚、二苯基醚、甲基第三丁基醚、異丙基乙基醚、二烷、二甘二甲醚、二甲甘醇、二甲氧基乙烷(DME)或THF；腈如甲腈、丁腈或苯基腈；醯胺如二甲基甲醯胺(DMF)或N－甲基吡咯啶酮(NMP)或此等溶劑之混合物，特佳係THF、DME、二乙醚。該反應可在過量羧酸酯(如在乙基醋酸酯)中進行。
較佳係使用等莫耳量之鹼及羧酸酯。或者，亦可使用過量之鹼。根據本發明，鹼：羧酸酯之比例係介於1.5：1與0.9：1之間，較佳係介於1.4：1，更佳係介於1.3：1與1.05：1之間。
在一根據本發明方法之較佳具體實施例中，起初將羧酸酯整批裝入或溶於適合溶劑中並逐漸與鹼混合，然後與
α,α－二鹵胺反應。
由於α,α－二鹵胺之水解敏感性，該反應應在惰性氣體氛圍下無水裝置中進行。
本發明將參照下列工作實例詳細說明，但不受其所限。
實例1：乙基三氟乙醯醋酸酯之製備
起初裝入之48克醋酸乙酯在RT下與10%32.4克乙氧化鈉於乙醇中之溶液混合。該混合物在RT下攪拌1小時，然後與36克1,1,2,2－四氟乙基二甲基胺混合。接著，該溶液在30℃下攪拌2小時，與H2
O混合並調整至pH 5。以醋酸乙酯萃取並接著蒸餾後，獲得27克(65%)二氟乙醯醋酸乙酯(沸點90－94℃/100毫巴)。
實例2：
類似實例1，除了使用氫化鈉取代乙氧化鈉。所得產率為79%。
實例3：
類似實例1，除了使用1,1－二氯－2,2－二氟乙基二甲基胺(由N,N－二甲基二氟乙醯胺與草醯基氯在80℃下製得)之外。所得產率為63%。
Claims (6)
- 一種製備式(I)之烷基二鹵乙醯醋酸酯之方法，
- 根據申請專利範圍第1項之方法，其特徵在於X 係選自氟或氯；X’ 係氟；R1 係選自氫或氟；R2 係氫；R3 係選自甲基或乙基；R4 係選自甲基或乙基；R5 係選自甲基或乙基。
- 根據申請專利範圍第1項之方法，其特徵在於X 係氟；X’ 係氟；R1 係氫；R2 係氫；R3 係乙基；R4 係甲基；R5 係甲基。
- 根據申請專利範圍第1項之方法，其特徵在於該α,α-二鹵胺係選自由1,1,2,2-四氟乙基-N,N-二甲基胺、 1,1,2,2-四氟乙基-N,N-二乙基胺、1,1,2-三氟-2-(三氟甲基)乙基-N,N-二甲基胺、1,1,2-三氟-2-(三氟甲基)乙基-N,N-二乙基胺(Ishikawa試劑)、1,1,2-三氟-2-氯乙基-N,N-二甲基胺及1,1,2-三氟-2-氯乙基-N,N-二乙基胺(Yarovenko試劑)組成之群。
- 根據申請專利範圍第1項之方法，其特徵在於該鹼係選自由鹼金屬氫氧化物、鹼金屬烷氧化物、氫化物、烷基鋰試劑及Grignard試劑或其混合物組成之群。
- 根據申請專利範圍第1項之方法，其特徵在於該羧酸酯係選自乙酸甲酯、乙酸乙酯、氟醋酸乙酯、溴醋酸乙酯、丙酸乙酯及苯基醋酸乙酯。
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| WO2006005612A1 (en) * | 2004-07-14 | 2006-01-19 | Syngenta Participations Ag | Process for the preparation of 4,4-difluoro-3-oxobutanoic acid esters |
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| WO2008092583A3 (de) | 2008-09-18 |
| CN101595081A (zh) | 2009-12-02 |
| EP2114855B1 (de) | 2016-07-27 |
| TW200846318A (en) | 2008-12-01 |
| WO2008092583A2 (de) | 2008-08-07 |
| CN101595081B (zh) | 2014-04-23 |
| US8044231B2 (en) | 2011-10-25 |
| ES2597853T3 (es) | 2017-01-23 |
| EP2114855A2 (de) | 2009-11-11 |
| JP5264780B2 (ja) | 2013-08-14 |
| WO2008092583A8 (de) | 2009-12-03 |
| DK2114855T3 (en) | 2016-11-07 |
| US20100121095A1 (en) | 2010-05-13 |
| DE102007005296A1 (de) | 2008-08-07 |
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