CN106414389A - 从1,1,1‑三氟丙酮制备4‑烷氧基‑1,1,1‑三氟丁‑3‑烯‑2‑酮的方法 - Google Patents
从1,1,1‑三氟丙酮制备4‑烷氧基‑1,1,1‑三氟丁‑3‑烯‑2‑酮的方法 Download PDFInfo
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- CN106414389A CN106414389A CN201580025253.7A CN201580025253A CN106414389A CN 106414389 A CN106414389 A CN 106414389A CN 201580025253 A CN201580025253 A CN 201580025253A CN 106414389 A CN106414389 A CN 106414389A
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- 238000000034 method Methods 0.000 title claims abstract description 27
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 5
- 239000011592 zinc chloride Substances 0.000 claims description 5
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000001110 calcium chloride Substances 0.000 claims description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910015844 BCl3 Inorganic materials 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims description 3
- 229910015845 BBr3 Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 6
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 5
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical class C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 5
- -1 alkene ethers Chemical class 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000006353 environmental stress Effects 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 150000002373 hemiacetals Chemical class 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical class CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 3
- JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- UJJMLGJZQGGQAZ-UHFFFAOYSA-N 2-(fluoromethyl)pyridine Chemical compound FCC1=CC=CC=N1 UJJMLGJZQGGQAZ-UHFFFAOYSA-N 0.000 description 1
- HTSVYUUXJSMGQC-UHFFFAOYSA-N 2-chloro-1,3,5-triazine Chemical compound ClC1=NC=NC=N1 HTSVYUUXJSMGQC-UHFFFAOYSA-N 0.000 description 1
- WYLIRYQDDKDHLT-UHFFFAOYSA-N CC1=CC=CC=C1C.CC1=CC=CC=C1C Chemical compound CC1=CC=CC=C1C.CC1=CC=CC=C1C WYLIRYQDDKDHLT-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000011040 TRPV Cation Channels Human genes 0.000 description 1
- 108010062740 TRPV Cation Channels Proteins 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JQOAQUXIUNVRQW-UHFFFAOYSA-N hexane Chemical class CCCCCC.CCCCCC JQOAQUXIUNVRQW-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 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
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0231—Halogen-containing compounds
- B01J31/0232—Halogen-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0228
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Liquid Crystal Substances (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开一种用于从1,1,1‑三氟丙酮制备4‑烷氧基‑1,1,1‑三氟丁‑3‑烯‑2‑酮的方法。
Description
技术领域
本发明公开了一种从1,1,1-三氟丙酮制备4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的方法。
背景技术
式(I)的4-烷氧基-1,1,1-三氟丁-3-烯-2-酮和4-芳氧基-1,1,1-三氟丁-3-烯-2-酮是制备氟化杂环的重要合成中间体。
2-三氟甲基吡啶和6-三氟甲基吡啶-3-甲酸衍生物是制备生物活性化合物的中间体。例如，WO 00/39094 A1公开了三氟甲基吡啶用作为除草剂，WO 2006/059103 A2公开了三氟甲基吡啶用作为在药物、化学产品和农业化学产品的生产中的中间体，WO 2008/013414 A1公开了三氟甲基吡啶用作为辣椒素受体拮抗剂和WO 2012/061926 A1描述了三氟甲基吡啶用作为钙通道阻滞剂。
WO 2005/026149 A、DE 24 29 674 A和EP 51 209 A公开了一些在本发明中使用的前体。
Okada等,Heterocycles 1997,46,129-132首次报导了制备6-三氟甲基吡啶-3-甲酸衍生物的常用路线，其只被其他人略微修改过。该常用合成策略概述于方案1：
该路线在大规模生产6-三氟甲基吡啶-3-甲酸衍生物方面存在不足之处，这是因为乙基乙烯基醚高度易燃，因而难以处理，以及因为三氟乙酰基化的烯醇醚和三氟乙酰基化的烯胺的中间体是不稳定的，且不能储存较长时间。而且，大多数烯基醚是致突变的。
US 20130079377描述了用于合成新颖辣椒素受体配体的起始于4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的乙烯基醚的制备方法和用途。
US 20120101305公开了从乙烯基醚和三氟乙酰氯制备4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的方法。
US 20140051892 A1公开了制备4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的方法，其通过使三氟乙酰氯与乙基乙烯基醚反应，然后热分解所述得到的氯化中间体来实施。该方法的缺点是形成氯化氢，其具有腐蚀性并可导致产物不耐贮藏。
WO 2004/078729 A1公开了从尤其是4-烷氧基-1,1,1-三氟丁-3-烯-2-酮制备式(Xa)化合物的方法：
并在第18页实施例P2中公开了4-乙氧基-1,1,1-三氟丁-3-烯-2-酮用于制备式(X-1)化合物的用途：
式(Xa)化合物和式(X-1)化合物是用于制备除草剂的中间体。
所有已知的针对4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的路线是以乙烯基醚与三氟乙酰氯或三氟乙酸酐的反应为基础的，由此形成一个当量的HCl或三氟乙酸作为副产物，该副产物通常必须通过添加碱来去除，以防止所述酸介导降解所述产物。该合成策略在用于大规模生产4-烷氧基-1,1,1-三氟丁-3-烯-2-酮方面的进一步缺点是乙烯基醚的高度易燃性和致突变性。
需要一种改善的制备4-烷氧基-1,1,1-三氟丁-3-烯-2-酮的方法。这种方法不需要使用所述存在问题的三氟乙酰氯和乙基乙烯基醚。如下文概述的本发明的方法满足这些要求。
发明内容
相比于现有技术，本发明的方法提供一些优点：其允许获得4-烷氧基-1,1,1-三氟丁-3-烯-2-酮，而不会形成氯化氢。仅形成的副产物是乙酸、乙酸乙酯和甲酸乙酯，从而允许使用不耐HCl的反应器。重要的是，不需要使用存在问题的乙烯基醚。而且，本发明的方法仅包括一个合成步骤，因而相比于US 20140051892 A1中描述的两步骤的方法其成本较少。
除非另外说明，否则在下文中：
环境压强 通常为1巴，随天气不同而变化；
卤素 是指F、Cl、Br或I，优选Cl、Br或I；
烷基 是指直链或支链烷基，烷基的实例包括甲基、乙基、正丙基、异丙基、正丁基、仲丁基、叔丁基、戊基、己基、庚基等等；
环烷基或环状烷基 包括脂环残基、双环脂环残基和三环脂环残基；“环烷基”的实例包括环丙基、环丁基、环戊基、环己基、环庚基、降冰片基和金刚烷基；
烷氧基 是指烷基-O，即通过从脂肪醇去除与氧结合的氢而获
得的基团；
(烷氧基)烷氧基 是指烷氧基，其中烷基经另一烷氧基取代；(烷氧基)
烷氧基的实例包括具有式MeO-CH2-O-的甲氧基甲氧
基，具有式MeO-CH2-CH2-O-的2-(甲氧基)乙氧基，和
具有式(C3H5)CH2-O-CH2-CH2-O-的2-(环丙基甲氧基)乙
氧基；
Ac 乙酰基；
tBu 叔丁基
氰脲酰氯 2,4,6-三氯-1,3,5-三嗪
DBU 1,8-二氮杂双环[5.4.0]十一碳-7-烯；
DABCO 1,4-二氮杂双环[2.2.2]辛烷；
DMF N,N-二甲基甲酰胺
DMA N,N-二甲基乙酰胺；
DMSO 二甲亚砜；
卤素 是指F、Cl、Br或J，优选F、Cl或Br；
半缩醛 是指醇(例如甲醇或乙醇)与酮或醛的加成物；半缩醛
还可在将水添加至烯醇醚之后产生；例如，甲醇与
1,1,1-三氟丙酮的半缩醛是F3C-C(OH)(OCH3)-CH3；
己烷 己烷同分异构体的混合物；
水合物 是指水与酮或醛的加合物，例如1,1,1-三氟丙酮的水合
物是F3C-C(OH)2-CH3；
LDA 二异丙基氨基锂
NMP N-甲基-2-吡咯烷酮；
氨基磺酸 HO-SO2-NH2；
Temp 温度；
TriFA 1,1,1-三氟丙酮；
THF 四氢呋喃；
三氟丙酮 1,1,1-三氟丙-2-酮；
二甲苯 1,2-二甲基苯，1,3-二甲基苯，1,4-二甲基苯或其混合
物。
本发明的主题是制备式(I)化合物的方法：
所述方法包括步骤StepS1；步骤StepS1包括反应ReacS1；
反应ReacS1是在式(IV)化合物的存在下式(II)化合物与1,1,1-三氟丙酮发生的反应，
其中，
R1是C1-4烷基，
R4和R5相同或不同，且彼此独立地选自H和C1-4烷基。
具体实施方式
对于所述反应ReacS1，可以任何顺序混合式(II)化合物、1,1,1-三氟丙酮和式(IV)化合物。
优选地，R1选自：甲基、乙基、正丙基、异丙基和正丁基；
更优选地，R1选自：甲基、乙基和正丙基；
甚至更优选地，R1是甲基或乙基；
尤其是，R1是乙基。
优选地，R4和R5相同或不同，且彼此独立地选自H和C1-2烷基；
更优选地，R4和R5相同或不同，且彼此独立地选自H和甲基；
甚至更优选地，R4和R5相同或不同，且彼此独立地是氢或甲基；
尤其是，R4和R5是甲基。
优选地，化合物(II)的摩尔量是1,1,1-三氟丙酮的摩尔量的1-20倍，更优选为1-10倍，以及甚至更优选为1-6倍。
优选地，化合物(IV)的摩尔量是1,1,1-三氟丙酮的摩尔量的2-60倍，更优选为2-20倍，以及甚至更优选为2-10倍。
反应ReacS1可在催化剂CatS1的存在下进行；
催化剂CatS1选自：三氟乙酸、硫酸、ZnCl2、ZnBr2、ZnI2、BF3、BF3OEt2、BBr3、BCl3、MgCl2和CaCl2；
优选地，催化剂CatS1选自：三氟乙酸、硫酸、ZnCl2、ZnBr2、ZnI2、BF3OEt2、BCl3、MgCl2和CaCl2；
更优选地，催化剂CatS1选自：三氟乙酸、硫酸、ZnCl2、BF3OEt2、
MgCl2和CaCl2；
甚至更优选地，催化剂CatS1选自：三氟乙酸、ZnCl2、BF3OEt2和MgCl2。
优选地，催化剂CatS1的摩尔量是1,1,1-三氟丙酮的摩尔量的0.001-2倍，更优选为0.005-1倍，以及甚至更优选为0.01-0.5倍。
优选地，反应ReacS1是在0℃至250℃的温度进行，更优选在20℃至200℃的温度进行，甚至更优选在60℃至150℃的温度进行。
优选地，反应ReacS1在环境压强至150巴的压强下进行，更优选在环境压强至100巴的压强下进行，甚至更优选在环境压强至70巴的压强下进行。
优选地，反应ReacS1的反应时间是10分钟至72小时，更优选为1小时至48小时，甚至更优选为2小时至24小时。
反应(ReacS1)在溶剂中进行；
优选地，所述溶剂是溶剂(SolvS1)，且溶剂(SolvS1)选自：乙酸乙酯、乙酸丁酯、二氯甲烷、1,2-二氯乙烷、氯仿、乙腈、丙腈、DMF、DMA、DMSO、环丁砜、THF、2-甲基-THF、3-甲基-THF、二氧己环、1,2-二甲氧基乙烷、甲苯、苯、氯苯、硝基苯及其混合物；
更优选地，溶剂(SolvS1)选自：乙酸乙酯、乙酸丁酯、二氯甲烷、1,2-二氯乙烷、乙腈、丙腈、DMF、DMA、DMSO、环丁砜、THF、2-甲基-THF、3-甲基-THF、二氧己环、1,2-二甲氧基乙烷、甲苯、苯、氯苯及其混合物；
甚至更优选地，溶剂(SolvS1)选自：乙酸乙酯、乙酸丁酯、二氯甲烷、1,2-二氯乙烷、乙腈、DMF、DMA、环丁砜、二氧己环、1,2-二甲氧基乙烷、甲苯、氯苯及其混合物；
尤其是，溶剂(SolvS1)选自：乙酸乙酯、乙酸丁酯、二氯甲烷、1,2-二氯乙烷、乙腈、DMF、DMA、二氧己环、1,2-二甲氧基乙烷、甲苯、氯苯及其混合物。
优选地，溶剂(SolvS1)的重量是1,1,1-三氟丙酮的重量的0.1-100倍，更优选为1-50倍，甚至更优选为1-25倍。
在反应ReacS1之后，可通过过滤移除任意催化剂CatS1。
在所述反应ReacS1之后，可通过任意常规方法分离式(I)化合物，所述常规方法为例如在减压下蒸馏或结晶。优选地，蒸馏除去任意挥发性副产物，并纯化残留物，或者无需进一步纯化而使用残留物。
实施例
实施例1
在密闭管瓶中在140℃搅拌1,1,1-三氟丙酮(0.80ml,8.93mmol)、原甲酸三乙酯(2.23ml,13.0mmol)和乙酸酐(2.53ml,27.0mmol)的混合物，持续16小时。
通过1H NMR(CDCl3)分析样本，结果表明形成相对于使用的1,1,1-三氟丙酮而言收率为65％的式(1)化合物。
实施例2-5
以与实施例1相同的方式进行实施例2-5，任意不同之处列于表1中。
| 表1 | |||||||
| 实施例 | HC(OEt)3 | TriFA | Ac2O | 摩尔比例 | 温度 | 时间 | 收率 |
| [mmol] | [mmol] | [mmol] | (II)/TriFA/(IV) | [℃] | [h] | [％] | |
| 2 | 18 | 4.5 | 27 | 4/1/6 | 140 | 10 | 41 |
| 3 | 2.67 | 1.34 | 4 | 2/1/3 | 120 | 12 | 15 |
| 4 | 7.07 | 3.57 | 10.7 | 2/1/3 | 130 | 21 | 37 |
| 5 | 6.68 | 2.23 | 13.4 | 3/1/6 | 130 | 21 | 51 |
实施例6
在密闭管瓶中在140℃搅拌1,1,1-三氟丙酮(0.20ml,2.2mmol)、原甲酸三乙酯(1.0ml,9.1mmol)和乙酸酐(1.6ml,16.9mmol)的混合物，持续16小时。通过1H NMR(CDCl3)分析样本，结果表明形成相对于使用的三氟丙酮而言收率为78％的式(2)化合物。
1H NMR(CDCl3,400MHz)δ＝3.88(s,3H),5.87(d,J＝12Hz,1H),7.94(d,J＝12Hz,1H).
19F NMR(CDCl3)δ＝78.08ppm。
Claims (9)
1.制备式(I)化合物的方法，
所述方法包括步骤StepS1；步骤StepS1包括反应ReacS1；
反应ReacS1是在式(IV)化合物的存在下式(II)化合物与1,1,1-三氟丙酮发生的反应，
其中
R1是C1-4烷基，
R4和R5相同或不同，且彼此独立地选自H和C1-4烷基。
2.根据权利要求1所述的方法，其中R1选自：甲基、乙基、正丙基、异丙基和正丁基。
3.根据权利要求1或2所述的方法，其中R4和R5相同或不同，且彼此独立地选自H和C1-2烷基。
4.根据权利要求1-3中的任一项所述的方法，其中化合物(II)的摩尔量是1,1,1-三氟丙酮的摩尔量的1至20倍。
5.根据权利要求1-4中的任一项所述的方法，其中化合物(IV)的摩尔量是1,1,1-三氟丙酮的摩尔量的2至60倍。
6.根据权利要求1-5中的任一项所述的方法，其中反应ReacS1是在催化剂CatS1的存在下进行；催化剂CatS1选自：三氟乙酸、硫酸、ZnCl2、ZnBr2、ZnI2、BF3、BF3OEt2、BBr3、BCl3、MgCl2和CaCl2。
7.根据权利要求1-6中的任一项所述的方法，其中催化剂CatS1的摩尔量是1,1,1-三氟丙酮的摩尔量的0.001至2倍。
8.根据权利要求1-7中的任一项所述的方法，其中反应ReacS1是在0℃至250℃的温度进行。
9.根据权利要求1-8中的任一项所述的方法，其中反应ReacS1的反应时间是10分钟至72小时。
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| CA2953019A1 (en) | 2015-12-30 |
| MX2016017019A (es) | 2017-05-12 |
| CN106414389B (zh) | 2018-03-02 |
| IL249620A0 (en) | 2017-03-01 |
| TW201625511A (zh) | 2016-07-16 |
| KR101737296B1 (ko) | 2017-05-17 |
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