CN108976170A - A kind of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives and synthetic method - Google Patents
A kind of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives and synthetic method Download PDFInfo
- Publication number
- CN108976170A CN108976170A CN201810922766.3A CN201810922766A CN108976170A CN 108976170 A CN108976170 A CN 108976170A CN 201810922766 A CN201810922766 A CN 201810922766A CN 108976170 A CN108976170 A CN 108976170A
- Authority
- CN
- China
- Prior art keywords
- trifluoromethyl
- phenyl
- imidazoline
- ketone derivatives
- synthetic method
- 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
- 238000010189 synthetic method Methods 0.000 title claims abstract description 38
- -1 amidine salt Chemical class 0.000 claims abstract description 45
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 238000012545 processing Methods 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 135
- 238000006243 chemical reaction Methods 0.000 claims description 62
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 50
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 33
- 238000011097 chromatography purification Methods 0.000 claims description 25
- 239000003208 petroleum Substances 0.000 claims description 22
- 239000002585 base Substances 0.000 claims description 21
- 239000012046 mixed solvent Substances 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims description 16
- 125000006303 iodophenyl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 9
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 8
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 7
- 239000000284 extract Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 239000011630 iodine Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical group FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 125000001340 2-chloroethyl group Chemical class [H]C([H])(Cl)C([H])([H])* 0.000 claims 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 claims 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 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 1
- 239000012044 organic layer Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- 239000000575 pesticide Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract 1
- 229910052723 transition metal Inorganic materials 0.000 abstract 1
- 150000003624 transition metals Chemical class 0.000 abstract 1
- 239000000047 product Substances 0.000 description 66
- 238000007445 Chromatographic isolation Methods 0.000 description 19
- 238000010438 heat treatment Methods 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 238000003810 ethyl acetate extraction Methods 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000004293 19F NMR spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 238000012512 characterization method Methods 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910014263 BrF3 Inorganic materials 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229910020323 ClF3 Inorganic materials 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- SKOHOWAOVMUZJY-UHFFFAOYSA-N 3-(pyridin-3-ylmethoxymethyl)pyridine Chemical compound C=1C=CN=CC=1COCC1=CC=CN=C1 SKOHOWAOVMUZJY-UHFFFAOYSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- MZPVIVUTUMSQFY-UHFFFAOYSA-N 6-iodo-2-methyl-3-[3-(trifluoromethyl)phenyl]quinazolin-4-one Chemical compound CC1=NC2=CC=C(I)C=C2C(=O)N1C1=CC=CC(C(F)(F)F)=C1 MZPVIVUTUMSQFY-UHFFFAOYSA-N 0.000 description 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
- ISRONRXJJCUEMZ-UHFFFAOYSA-N CC(NC1=O)=NC1(C(F)(F)F)c1ccccc1 Chemical compound CC(NC1=O)=NC1(C(F)(F)F)c1ccccc1 ISRONRXJJCUEMZ-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- QXAITBQSYVNQDR-ZIOPAAQOSA-N amitraz Chemical compound C=1C=C(C)C=C(C)C=1/N=C/N(C)\C=N\C1=CC=C(C)C=C1C QXAITBQSYVNQDR-ZIOPAAQOSA-N 0.000 description 1
- 229960002587 amitraz Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to medication chemistry synthesis technical field, a kind of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives and synthetic method are disclosed.The synthetic method: in alkali and organic solvent, amidine salt being reacted with trifluoromethyl ketone compound, subsequent processing, obtains 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives.The structure of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives of the invention is Formulas I.The method of the present invention is avoided using transition-metal catalyst, raw materials used nontoxic, cheap and easy to get；It is good to functional group's adaptability to react, and to substrate wide adaptability, product yield high can be amplified to gram-grade large-scale production synthesis, be conducive to industrial production, and products therefrom has extensive use in pesticide, medicine and Material Field.
Description
Technical field
The invention belongs to materials, medication chemistry synthesis technical field, and in particular to a kind of 5- trifluoromethyl -4H- imidazoline -
4- ketone derivatives and synthetic method.
Background technique
Atomic radius very little in view of fluorine atom and there is high electronegativity again, is difficult to be polarized.Therefore, to organising
Fluorine atom or fluoro-containing group are introduced in adduct molecule would generally significantly improve the chemical property, physical property and life of compound
Object activity.According to statistics, in the pesticide or drug molecule of commercial type, 30% or more pesticide or drug molecule at least contains one
A fluorine atom or fluoro-containing group.However, the Fluorinated Pharmaceuticals Based On Natural Products type for being present in nature is extremely limited.In order to meet people
Production and research to organic fluoride-containing compound amounts and type increase there is an urgent need to development efficiently synthesizes organic fluoride-containing compound
Method, be always chemists' one of core missions urgently to be resolved.
In view of the significant application value in material, field of medicaments of 4H- imidazoline -4- ketone compound, the side of efficiently synthesizing
Method research is constantly subjected to people and widely pays close attention to.But 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives and its synthetic method
But it is not reported always, such compound and its synthetic technology research are still blank.Therefore, development efficiently synthesizes 5- fluoroform
The method of base -4H- imidazoline -4- ketone compound is still the research topic of a challenge at present.
Summary of the invention
In order to solve the blank of the above prior art, the primary purpose of the present invention is that 5- can be efficiently synthesized by providing one kind
Trifluoromethyl -4H- imidazoline -4- ketone derivatives.
Another object of the present invention is to provide the synthetic methods of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives.
The object of the invention is achieved through the following technical solutions:
5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, structure are Formulas I:
Wherein R1For phenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl, p-fluorophenyl, fluorophenyl, neighbour
Fluorophenyl, to iodophenyl, p-methylphenyl (p-methylphenyl), p-methoxyphenyl, to methyl mercapto phenyl, to Dimethylaminobenzene
Base, to cyano-phenyl, p-trifluoromethyl phenyl, to methylsulfonyl phenyl, to methyl formate base phenyl, p-nitrophenyl, to hydroxyl
Phenyl, 3,4- Dimethoxyphenyl, 3,4- dichlorophenyl, 2- naphthalene, 2- thienyl, 3- pyridyl group, 2- phenylethyl, methyl,
Ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl or tert-butyl；
R be phenyl, to iodophenyl, iodophenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl, to fluorobenzene
Base, fluorophenyl, o-fluorophenyl, p-methylphenyl, p-methoxyphenyl, to methyl formate base phenyl, hydrogen, methyl, ethyl, isopropyl
Base, cyclohexyl or tert-butyl.
The synthetic method of the 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
In alkali and organic solvent, amidine salt is reacted, subsequent processing with trifluoromethyl ketone compound, obtains 5- fluoroform
Base -4H- imidazoline -4- ketone derivatives；
The amidine salt isWherein, R1For phenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl,
P-fluorophenyl, fluorophenyl, o-fluorophenyl, to iodophenyl, p-methylphenyl, p-methoxyphenyl, to methyl mercapto phenyl, to diformazan
Aminophenyl, to cyano-phenyl, p-trifluoromethyl phenyl, to methylsulfonyl phenyl, to methyl formate base phenyl, p-nitrophenyl,
P-hydroxybenzene, 3,4- Dimethoxyphenyl, 3,4- dichlorophenyl, 2- naphthalene, 2- thienyl, 3- pyridyl group, 2- phenylethyl,
Methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl or tert-butyl；X is chlorine, bromine, iodine；
The trifluoromethyl ketone compound isWherein, R is phenyl, to iodophenyl, iodophenyl, right
Bromophenyl, m-bromophenyl, rubigan, chlorphenyl, p-fluorophenyl, fluorophenyl, o-fluorophenyl, p-methylphenyl, to methoxy
Base phenyl, to methyl formate base phenyl, hydrogen, methyl, ethyl, isopropyl, cyclohexyl or tert-butyl.
The molar ratio of the amidine salt and trifluoromethyl ketone compound is 1:(1~3).
The additional amount of alkali and the molar ratio of amidine salt are (1~4): 1.
The alkali is sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium acetate, potassium tert-butoxide
One or more of with sodium tert-butoxide.
The organic solvent is N,N-dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, toluene, benzene, diformazan
One or more of benzene, 1,2- dichloroethanes, tetrahydrofuran and acetonitrile.
The temperature of the reaction is 50~90 DEG C, time of reaction is 12~for 24 hours；The reaction is in air or oxygen atmosphere
Lower progress.
The subsequent processing refers to be cooled to room temperature after reaction, and water and organic solvent is added, and extracts reaction solution, will have
Machine layer carries out vacuum rotary steam and removes solvent, obtains crude product, obtains 5- trifluoromethyl -4H- imidazoline -4- ketone through column Chromatographic purification and spread out
Biology.The organic solvent is ethyl acetate, methylene chloride or ether.
The column Chromatographic purification refers to using petroleum ether: the mixed solvent of ethyl acetate is the column Chromatographic purification of eluent.Stone
Oily ether: the volume ratio of ethyl acetate is (2~100): 1.
Reaction equation involved in method of the invention:
Preparation method of the invention and obtained product have the following advantages that and the utility model has the advantages that
(1) synthetic method of the invention does not use catalyst, does not need ligand, raw materials used nontoxic, cheap and easy to get；Reaction
It is good to functional group's adaptability, to substrate wide adaptability, product yield high；
(2) synthetic method of the invention can be amplified to gram-grade large-scale production, and easy to operate, safety, reaction condition temperature
With, have good prospects for commercial application；
(3) products therefrom of the present invention has extensive use in pesticide, medicine and Material Field.
Detailed description of the invention
Fig. 1 is the hydrogen spectrogram of embodiment 1-8 products therefrom；
Fig. 2 is the carbon spectrogram of embodiment 1-8 products therefrom；
Fig. 3 is the fluorine spectrogram of embodiment 1-8 products therefrom.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
Embodiment 1
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, instead
It answers system to be stirred to react at 70 DEG C 12 hours, stops heating and stirring, be cooled to room temperature, water, ethyl acetate extraction reaction is added
Ethyl acetate layer is carried out vacuum rotary steam by liquid, removes solvent, then by column chromatographic isolation and purification, obtain target product, used
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 96%.
Embodiment 2
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.8 mM of potassium carbonate, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, reaction
System is stirred to react 12 hours at 70 DEG C, is stopped heating and stirring, is cooled to room temperature, and water is added, and ethyl acetate extracts reaction solution,
Ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, column layer used
Analysis eluent is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 65%.
Embodiment 3
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.2 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of Isosorbide-5-Nitrae-dioxane, reactant
It ties up to 70 DEG C to be stirred to react 12 hours, stops heating and stirring, be cooled to room temperature, water is added, ethyl acetate extracts reaction solution, will
Ethyl acetate layer carries out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, column chromatography used
Eluent is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 10%.
Embodiment 4
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.2 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, instead
It answers system to be stirred to react at 50 DEG C 12 hours, stops heating and stirring, be cooled to room temperature, water, ethyl acetate extraction reaction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product by liquid, used
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 21%.
Embodiment 5
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.6 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, instead
It answers system to be stirred to react at 90 DEG C 12 hours, stops heating and stirring, be cooled to room temperature, water, ethyl acetate extraction reaction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product by liquid, used
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 91%.
Embodiment 6
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrogen iodine is added
Hydrochlorate, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide,
Reaction system is stirred to react 12 hours at 70 DEG C, is stopped heating and stirring, is cooled to room temperature, and water is added, and ethyl acetate extraction is anti-
Liquid is answered, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, it is used
Column chromatographic eluate be petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 94%.
Embodiment 7
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under oxygen atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, instead
It answers system to be stirred to react at 70 DEG C 12 hours, stops heating and stirring, be cooled to room temperature, water, ethyl acetate extraction reaction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product by liquid, used
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 96%.
Embodiment 8
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 250 milliliters of reaction flasks equipped with reflux condensing tube, 5 mMs of benzenecarboximidamide hydrochloric acid are added
Salt, 12.5 mMs of potassium tert-butoxides, 10 mMs of 3- phenyl -1,1,1,-trifluoroacetone, 50 milliliters of n,N-Dimethylformamide,
Reaction system is stirred to react 12 hours at 70 DEG C, is stopped heating and stirring, is cooled to room temperature, and water is added, and ethyl acetate extraction is anti-
Liquid is answered, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, it is used
Column chromatographic eluate be petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 96%.
Hydrogen spectrogram, carbon spectrogram and the fluorine spectrogram of Examples 1 to 8 products therefrom major diastereomer are respectively such as Fig. 1, figure
Shown in 2 and Fig. 3；Its structural characterization data is as follows:
1H NMR(400MHz,d6- DMSO) δ 12.47 (s, 1H), 8.17 (d, J=7.6Hz, 2H), 7.97 (d, J=
6.8Hz, 2H), 7.71 (t, J=7.2Hz, 1H), 7.63 (t, J=7.6Hz, 2H), 7.47-7.52 (m, 3H)；
13C NMR(100MHz,d6-DMSO)δ178.4,164.7,133.5,132.0,130.0,129.5,129.1,
128.0,127.9,127.8,123.3(q,1JC-F=281.3Hz), 75.4 (q,2JC-F=27.4Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3187,1735,1629,1443,1257,1172cm-1；
HRMS(ESI,m/z):[M+H]+C16H11F3N2O+H, theoretical value 305.0896；Actual value, 305.0898.
Infer that the structure of Examples 1 to 8 products therefrom is shown below according to above data:
Embodiment 9
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 4- methoxybenzene is added
Amitraz hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl
Formamide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, water, ethyl acetate is added
Reaction solution is extracted, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target production
Object, column chromatographic eluate used are the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is
97%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.29 (s, 1H), 8.12 (d, J=5.2Hz, 2H), 7.93 (s, 2H), 7.47
(s, 3H), 7.15 (d, J=6.8Hz, 2H), 3.87 (s, 3H)；
13C NMR(100MHz,d6-DMSO)δ178.6,164.1,163.6,132.2,130.0,129.9,129.0,
127.8,123.3(q,1JC-F=281.4Hz), 119.9,114.9,75.0,56.0；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3062,2851,2743,1757,1609,1441,1262,1175cm-1；
HRMS(ESI,m/z):[M+H]+C17H13F3N2O2+ H, theoretical value 335.1002；Actual value, 335.1005.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 10
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 4- hydroxy benzenes first is added
Amidine hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl methyl
Amide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
It extracts reaction solution, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product,
Column chromatographic eluate used is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 60%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6-DMSO)δ12.23(s,1H),10.43(s,1H),7.91-8.01(m,4H),7.47-
7.47 (m, 3H), 6.97 (d, J=7.6Hz, 2H)；
13C NMR(100MHz,d6-DMSO)δ178.5,164.0,162.3,132.4,130.1,129.9,129.0,
127.9,123.4(q,1JC-F=281.5Hz), 118.4,116.2,75.2 (q,2JC-F=27.1Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3459,3131,2843,1745,1608,1458,1263,1177cm-1；
HRMS(ESI,m/z):[M+H]+C16H11F3N2O2+ H, theoretical value is 321.0845；Actual value, 321.0850.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 11
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 4- bromobenzene carbonamidine is added
Hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl formyl
Amine, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, institute by reaction solution
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 94%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.53 (s, 1H), 8.11 (d, J=7.6Hz, 2H), 7.97 (d, J=
6.0Hz, 2H), 7.85 (d, J=7.6Hz, 2H), 7.51-7.52 (m, 3H)；
13C NMR(100MHz,d6-DMSO)δ178.4,164.2,132.6,131.8,130.0,130.0,129.1,
127.9,127.5,126.9,123.1(q,1JC-F=281.5Hz), 75.4 (q,2JC-F=27.9Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3178,1733,1626,1436,1251,1176cm-1；
HRMS(ESI,m/z):[M+H]+C16H10BrF3N2O+H, theoretical value 383.0001；Actual value, 383.0002
Infer that the structure of the present embodiment products therefrom major diastereomer is shown below according to above data:
Embodiment 12
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 4- nitrobenzoyl is added
Amidine hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl methyl
Amide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
It extracts reaction solution, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product,
Column chromatographic eluate used is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 85%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.73 (s, 1H), 8.39-8.47 (m, 4H), 7.94 (d, J=6.8Hz,
2H),7.51-7.52(m,3H)；
13C NMR(100MHz,d6-DMSO)δ178.2,163.8,150.5,133.3,131.5,130.2,129.6,
129.2,127.8,124.6,123.1(q,1JC-F=281.5Hz), 75.7 (q,2JC-F=26.7Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3173,3106,2883,1737,1610,1531,1442,1349,1255,1175cm-1；
HRMS(ESI,m/z):[M+H]+C16H10F3N3O3+ H, theoretical value 350.0747；Actual value, 350.0750.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 13
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 3- picolyl ether is added
Hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl formyl
Amine, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, institute by reaction solution
Column chromatographic eluate is the petroleum ether that volume ratio is 2:1: ethyl acetate mixed solvent；The yield of product is 86%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.60 (s, 1H), 9.29 (s, 1H), 8.87 (d, J=2.8Hz, 1H), 8.51
(d, J=7.6Hz, 1H), 7.94 (d, J=5.2Hz, 2H), 7.67 (s, 1H), 7.50 (s, 3H)；
13C NMR(100MHz,d6-DMSO)δ178.3,163.7,154.0,148.9,135.6,131.7,130.1,
129.1,127.9,124.5,124.0,123.1(q,1JC-F=278.1Hz), 75.3 (q,2JC-F=27.9Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.4 (s, 3F)；
IR(KBr):3443,3064,1756,1615,1476,1267,1173cm-1；
HRMS(ESI,m/z):[M+H]+C15H10F3N3O+H, theoretical value 306.0849；Actual value, 306.0853.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 14
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of ethanamidine hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of n,N-Dimethylformamide, instead
It answers system to be stirred to react at 70 DEG C 12 hours, stops heating and stirring, be cooled to room temperature, water, ethyl acetate extraction reaction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product by liquid, used
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 39%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 11.63 (s, 1H), 7.81 (d, J=4.4Hz, 1H), 7.44-7.48 (m,
3H),2.22(s,3H)；
13C NMR(100MHz,d6-DMSO)δ177.8,166.5,131.8,129.9,129.0,127.9,123.2(q,1JC-F=280.9Hz), 75.2 (q,2JC-F=27.7Hz), 16.6；
19F NMR(376MHz,d6- DMSO) δ=- 73.8 (s, 3F)；
IR(KBr):3274,3058,2924,2848,1752,1643,1441,1260,1178cm-1；
HRMS(ESI,m/z):[M+H]+C11H9F3N2O+H, theoretical value 243.0740；Actual value, 243.0745.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 15
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 2- chlordimeform is added
Hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl formyl
Amine, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, institute by reaction solution
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 86%.
The structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.27 (s, 1H), 7.94 (d, J=8.0Hz, 2H), 7.76 (d, J=
7.6Hz,1H),7.63-7.70(m,2H),7.49-7.57(m,4H)；
13C NMR(100MHz,d6-DMSO)δ177.7,164.7,133.6,132.2,131.5,131.3,130.9,
130.1,129.2,128.5,128.1,127.9,123.0(q,1JC-F=281.3Hz), 75.6 (q,2JC-F=27.1Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3265,3070,1756,1624,1437,1257,1179cm-1；
HRMS(ESI,m/z):[M+H]+C16H10ClF3N2O+H, theoretical value 339.0507；Actual value, 339.0510.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 16
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of 3- bromobenzene carbonamidine is added
Hydrochloride, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- phenyl -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl formyl
Amine, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
Ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product, institute by reaction solution
Column chromatographic eluate is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 85%.
The structural characterization data of the present embodiment products therefrom major diastereomer are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.50 (s, 1H), 8.32 (s, 1H), 8.15 (d, J=7.6Hz, 1H),
7.90-7.93 (m, 3H), 7.59 (t, J=8.0Hz, 1H), 7.49-7.52 (m, 3H)；
13C NMR(100MHz,d6-DMSO)δ178.2,163.7,136.3,132.7,131.7,131.7,130.5,
130.1,129.9,129.2,127.9,127.1,123.1(q,1JC-F=281.4Hz), 122.7,75.5 (q,2JC-F=
24.1Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.5 (s, 3F)；
IR(KBr):3442,3201,1738,1627,1448,1257,1174cm-1；
HRMS(ESI,m/z):[M+H]+C16H10BrF3N2O+H, theoretical value 383.0001；Actual value, 383.0005.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 17
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- (4- methoxyphenyl) -1,1,1,-trifluoroacetone, 2 milliliters of N, N- diformazan
Base formamide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, water, acetic acid second is added
Ester extracts reaction solution, and ethyl acetate layer is carried out vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target production
Object, column chromatographic eluate used are the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is
91%.
The main structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.41 (s, 1H), 8.14 (d, J=7.6Hz, 2H), 7.84 (d, J=
8.8Hz, 2H), 7.70 (t, J=7.6Hz, 1H), 7.62 (t, J=7.2Hz, 2H), 7.05 (d, J=8.8Hz, 2H), 3.79 (s,
3H)；
13C NMR(100MHz,d6-DMSO)δ178.7,164.4,160.6,133.5,129.5,129.2,128.0,
127.8,123.7,123.3(q,1JC-F=281.2Hz), 114.5,75.1 (q,2JC-F=27.4Hz), 55.7；
19F NMR(376MHz,d6- DMSO) δ=- 73.8 (s, 3F)；
IR(KBr):3175,2933,1738,1622,1509,1453,1252,1171cm-1；
HRMS(ESI,m/z):[M+H]+C17H13F3N2O2+ H, theoretical value 335.1002；Actual value, 335.1006.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 18
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- (4- iodophenyl) -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl methyl
Amide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
It extracts reaction solution, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product,
Column chromatographic eluate used is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 91%.
The main structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.50 (s, 1H), 8.13 (d, J=7.2Hz, 2H), 7.87 (d, J=
8.0Hz, 2H), 7.67-7.71 (m, 3H), 7.60 (t, J=7.2Hz, 2H)；
13C NMR(100MHz,d6-DMSO)δ178.1,165.1,138.0,133.6,131.7,130.0,129.5,
128.1,127.6,122.9(q,1JC-F=281.5Hz), 97.2,75.1 (q,2JC-F=27.8Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.6 (s, 3F)；
IR(KBr):3194,2921,1737,1628,1458,1251,1175cm-1；
HRMS(ESI,m/z):[M+H]+C16H10F3IN2O+H, theoretical value 430.9863；Actual value 430.9864.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
Embodiment 19
A kind of synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, comprising the following steps:
Under air atmosphere, in 25 milliliters of reaction flasks equipped with reflux condensing tube, 0.2 mM of benzenecarboximidamide hydrochloric acid is added
Salt, 0.5 mM of potassium tert-butoxide, 0.4 mM of 3- (3- chlorphenyl) -1,1,1,-trifluoroacetone, 2 milliliters of N, N- dimethyl methyl
Amide, reaction system are stirred to react 12 hours at 70 DEG C, are stopped heating and stirring, are cooled to room temperature, and water, ethyl acetate extraction is added
It extracts reaction solution, ethyl acetate layer is subjected to vacuum rotary steam and removes solvent, then by column chromatographic isolation and purification, obtains target product,
Column chromatographic eluate used is the petroleum ether that volume ratio is 10:1: ethyl acetate mixed solvent；The yield of product is 80%.
The main structural characterization data of the present embodiment products therefrom are as follows:
1H NMR(400MHz,d6- DMSO) δ 12.58 (s, 1H), 8.18 (d, J=7.2Hz, 2H), 7.94 (s, 2H),
7.58-7.72(m,5H)；
13C NMR(100MHz,d6-DMSO)δ177.9,165.3,134.0,133.8,133.7,131.1,130.2,
129.5,128.1,127.6,126.7,123.0(q,1JC-F=281.5Hz), 74.8 (q,2JC-F=27.6Hz)；
19F NMR(376MHz,d6- DMSO) δ=- 73.7 (s, 3F)；
IR(KBr):3187,2924,1736,1631,1457,1255,1177cm-1；
HRMS(ESI,m/z):[M+H]+C16H10ClF3N2O+H, theoretical value 339.0507；Actual value, 339.0508.
Infer that the structure of the present embodiment products therefrom is shown below according to above data:
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. a kind of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives, it is characterised in that: its structure is Formulas I:
Wherein R1For phenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl, p-fluorophenyl, fluorophenyl, adjacent fluorobenzene
Base, to iodophenyl, p-methylphenyl, p-methoxyphenyl, to methyl mercapto phenyl, to dimethylamino phenyl, to cyano-phenyl, to three
Trifluoromethylphenyl, to methylsulfonyl phenyl, to methyl formate base phenyl, p-nitrophenyl, p-hydroxybenzene, 3,4- dimethoxy benzene
Base, 3,4- dichlorophenyl, 2- naphthalene, 2- thienyl, 3- pyridyl group, 2- phenylethyl, methyl, ethyl, propyl, isopropyl, ring
Propyl, cyclobutyl or tert-butyl；
R is phenyl, to iodophenyl, iodophenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl, p-fluorophenyl,
Fluorophenyl, o-fluorophenyl, p-methylphenyl, p-methoxyphenyl, to methyl formate base phenyl, hydrogen, methyl, ethyl, isopropyl, ring
Hexyl or tert-butyl.
2. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 1, it is characterised in that:
The following steps are included:
In alkali and organic solvent, amidine salt is reacted, subsequent processing with trifluoromethyl ketone compound, obtains 5- trifluoromethyl-
4H- imidazoline -4- ketone derivatives；
The amidine salt isWherein, R1For phenyl, p-bromophenyl, m-bromophenyl, rubigan, chlorphenyl, to fluorine
Phenyl, fluorophenyl, o-fluorophenyl, to iodophenyl, p-methylphenyl, p-methoxyphenyl, to methyl mercapto phenyl, to dimethylamino
Phenyl, to cyano-phenyl, p-trifluoromethyl phenyl, to methylsulfonyl phenyl, to methyl formate base phenyl, p-nitrophenyl, to hydroxyl
Base phenyl, 3,4- Dimethoxyphenyl, 3,4- dichlorophenyl, 2- naphthalene, 2- thienyl, 3- pyridyl group, 2- phenylethyl, first
Base, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl or tert-butyl；X is chlorine, bromine, iodine；
The trifluoromethyl ketone compound isWherein, R be phenyl, to iodophenyl, iodophenyl, to bromobenzene
Base, m-bromophenyl, rubigan, chlorphenyl, p-fluorophenyl, fluorophenyl, o-fluorophenyl, p-methylphenyl, to methoxybenzene
Base, to methyl formate base phenyl, hydrogen, methyl, ethyl, isopropyl, cyclohexyl or tert-butyl.
3. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The molar ratio of the amidine salt and trifluoromethyl ketone compound is 1:(1~3).
4. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The molar ratio of alkali and amidine salt is (1~4): 1.
5. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The alkali is sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium acetate, potassium tert-butoxide and the tert-butyl alcohol
One or more of sodium.
6. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The organic solvent is N,N-dimethylformamide, dimethyl sulfoxide, 1,4- dioxane, toluene, benzene, dimethylbenzene, 1,2- bis-
One or more of chloroethanes, tetrahydrofuran and acetonitrile.
7. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The temperature of the reaction is 50~90 DEG C, time of reaction is 12~for 24 hours；The reaction carries out under air or oxygen atmosphere.
8. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 2, it is characterised in that:
The subsequent processing refers to be cooled to room temperature after reaction, and water and organic solvent is added, and extracts reaction solution, organic layer is carried out
Vacuum rotary steam removes solvent, obtains crude product, obtains 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives through column Chromatographic purification.
9. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 8, it is characterised in that:
The organic solvent is ethyl acetate, methylene chloride or ether；
The column Chromatographic purification refers to using petroleum ether: the mixed solvent of ethyl acetate is the column Chromatographic purification of eluent.
10. the synthetic method of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives according to claim 9, it is characterised in that:
Petroleum ether: the volume ratio of ethyl acetate is (2~100): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922766.3A CN108976170B (en) | 2018-08-14 | 2018-08-14 | 5-trifluoromethyl-4H-imidazoline-4-ketone derivative and synthetic method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810922766.3A CN108976170B (en) | 2018-08-14 | 2018-08-14 | 5-trifluoromethyl-4H-imidazoline-4-ketone derivative and synthetic method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108976170A true CN108976170A (en) | 2018-12-11 |
| CN108976170B CN108976170B (en) | 2022-04-22 |
Family
ID=64552665
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810922766.3A Expired - Fee Related CN108976170B (en) | 2018-08-14 | 2018-08-14 | 5-trifluoromethyl-4H-imidazoline-4-ketone derivative and synthetic method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108976170B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109608323A (en) * | 2019-01-07 | 2019-04-12 | 华南理工大学 | A kind of β-trifluoromethyl-beta-hydroxy substituted cyclohexanone derivative and its synthetic method |
| CN110642748A (en) * | 2019-09-20 | 2020-01-03 | 华南理工大学 | O- (2-trifluoromethyl-2-hydroxyethyl) oxime ether derivative and synthetic method and application thereof |
| CN113087667A (en) * | 2021-03-24 | 2021-07-09 | 五邑大学 | Synthesis method of imidazolidinone derivative |
| CN114539157A (en) * | 2022-03-03 | 2022-05-27 | 曲靖师范学院 | Method for preparing 4-iodo-N-arylpyrazole compound by iodine-promoted oxidation method |
| CN115093372A (en) * | 2022-06-16 | 2022-09-23 | 安徽工程大学 | Synthesis method of imidazole derivative |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6037474A (en) * | 1998-03-27 | 2000-03-14 | Degussa-Huuls | Process for the preparation of cyclic 4-oxoamidines |
| WO2006125592A2 (en) * | 2005-05-24 | 2006-11-30 | Lek Pharmaceuticals D.D. | Process for the preparation of 2-alkyl-1-((2'-substituted-biphenyl-4-yl)methyl)-imidazole, dihydroimidazole or benzimidazole derivatives |
| WO2007061600A1 (en) * | 2005-11-22 | 2007-05-31 | Amgen, Inc. | CATALYZED PROCESS OF MAKING C-5-SUBSTITUTED HETEROCYCLIC INHIBITORS OF 11ß-HYDROXY STEROID DEHYDROGENASE TYPE 1 |
| CN104177298A (en) * | 2014-09-18 | 2014-12-03 | 湘潭大学 | 4, 4-disubstituted-4, 5-dihydro-1H-imidazole-5-one and derivatives thereof as well as synthesis method thereof |
-
2018
- 2018-08-14 CN CN201810922766.3A patent/CN108976170B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6037474A (en) * | 1998-03-27 | 2000-03-14 | Degussa-Huuls | Process for the preparation of cyclic 4-oxoamidines |
| WO2006125592A2 (en) * | 2005-05-24 | 2006-11-30 | Lek Pharmaceuticals D.D. | Process for the preparation of 2-alkyl-1-((2'-substituted-biphenyl-4-yl)methyl)-imidazole, dihydroimidazole or benzimidazole derivatives |
| WO2007061600A1 (en) * | 2005-11-22 | 2007-05-31 | Amgen, Inc. | CATALYZED PROCESS OF MAKING C-5-SUBSTITUTED HETEROCYCLIC INHIBITORS OF 11ß-HYDROXY STEROID DEHYDROGENASE TYPE 1 |
| CN104177298A (en) * | 2014-09-18 | 2014-12-03 | 湘潭大学 | 4, 4-disubstituted-4, 5-dihydro-1H-imidazole-5-one and derivatives thereof as well as synthesis method thereof |
Non-Patent Citations (3)
| Title |
|---|
| ALEXEY YU. AKSINENKO ET AL.: "Carbamoyl imines of methyl trifluoropyruvate in cyclocondensation and cycloaddition reactions", 《JOURNAL OF FLUORINE CHEMISTRY》 * |
| N. SEWALD AND K. BURGER: "Reactions of 3,3,3-Trifluoropyruvates with Amidines- New Trifluoromethyl Substituted Heterocyclic "Building Blocks"", 《MONATSHEFTE FUR CHEMIE》 * |
| YANJUN XIE ET AL.: "Efficient 4,5-dihydro-1H-imidazol-5-one formation from amidines and ketones under transition-metal free conditions", 《GREEN CHEMISTRY》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109608323A (en) * | 2019-01-07 | 2019-04-12 | 华南理工大学 | A kind of β-trifluoromethyl-beta-hydroxy substituted cyclohexanone derivative and its synthetic method |
| CN109608323B (en) * | 2019-01-07 | 2021-07-20 | 华南理工大学 | Beta-trifluoromethyl-beta-hydroxy substituted cyclohexanone derivative and synthesis method thereof |
| CN110642748A (en) * | 2019-09-20 | 2020-01-03 | 华南理工大学 | O- (2-trifluoromethyl-2-hydroxyethyl) oxime ether derivative and synthetic method and application thereof |
| CN110642748B (en) * | 2019-09-20 | 2023-03-31 | 华南理工大学 | O- (2-trifluoromethyl-2-hydroxyethyl) oxime ether derivative and synthetic method and application thereof |
| CN113087667A (en) * | 2021-03-24 | 2021-07-09 | 五邑大学 | Synthesis method of imidazolidinone derivative |
| CN113087667B (en) * | 2021-03-24 | 2022-06-24 | 五邑大学 | Synthesis method of imidazolidinone derivative |
| CN114539157A (en) * | 2022-03-03 | 2022-05-27 | 曲靖师范学院 | Method for preparing 4-iodo-N-arylpyrazole compound by iodine-promoted oxidation method |
| CN114539157B (en) * | 2022-03-03 | 2023-12-22 | 曲靖师范学院 | Method for preparing 4-iodo-N-aryl pyrazole compound by iodine-promoted oxidation method |
| CN115093372A (en) * | 2022-06-16 | 2022-09-23 | 安徽工程大学 | Synthesis method of imidazole derivative |
| CN115093372B (en) * | 2022-06-16 | 2023-05-30 | 安徽工程大学 | Synthesis method of imidazole derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108976170B (en) | 2022-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108976170A (en) | A kind of 5- trifluoromethyl -4H- imidazoline -4- ketone derivatives and synthetic method | |
| CN106565648B (en) | The synthetic method of fluorine-containing alkyl-substituted 2,3- dihydro-benzofuran derivative and indole derivatives | |
| CN105693470A (en) | Continuous 3-methyl-3-buten-1-ol production method | |
| CN105152846A (en) | Method for efficiently preparing cylopropyl ethylnen | |
| CN102584718A (en) | Method for synthesizing quinazoline-4-(3H)-ketone | |
| CN105732619A (en) | Synthesizing method of 5,6,7,8-tetrahydropyridino-[2,3-d]pyrimidine compound | |
| CN104910036B (en) | A kind of containing continuous quaternary carbon center cyclopropane alpha-amino acid derivatives and synthetic method | |
| CN104628643B (en) | A kind of isoquinolines and the preparation method of derivative thereof | |
| CN109651191A (en) | A kind of difluoromethyl oxime ether derivatives and its synthetic method | |
| CN102775288A (en) | Synthetic method of chalcone compounds | |
| CN105061348B (en) | A kind of preparation method of 2 substituted benzene Bing oxazole compounds | |
| CN103896858B (en) | The preparation technology of cytosine | |
| CN109761918A (en) | A kind of fluoro- 1- aryl ethyl of N1-(2,2,2- tri-)-triazole derivatives and its synthetic method | |
| CN103694153B (en) | The method of styracin and arylsulfinate Reactive Synthesis alkenyl sulfone compound | |
| CN102718662A (en) | Method for preparing cinacalcet hydrochloride | |
| CN110590854B (en) | Triazole carbene palladium metal complex and preparation method and application thereof | |
| CN105037298B (en) | One kind replaces continuous quaternary carbon center propylene oxide derivatives and synthetic method containing trifluoromethyl | |
| CN109608323A (en) | A kind of β-trifluoromethyl-beta-hydroxy substituted cyclohexanone derivative and its synthetic method | |
| CN103923030A (en) | Synthesis method of key intermediate of anacetrapib | |
| CN101538253B (en) | Method for preparing repaglinide intermediate | |
| CN106699722A (en) | Synthetic method of 2,2-dichloro-1,3-benzodioxole-4-formaldehyde | |
| CN106588787B (en) | A kind of application of the triazole of 1,2,3- containing sweet-smelling formacyl ligand | |
| CN109705050A (en) | A method of synthesis 4- sulfenyl isoxazole | |
| CN108440384A (en) | The preparation method of the trifluoromethyl hydroxylation derivative of isoindolone | |
| CN109896944A (en) | A method of synthesis 1,4- naphthoquinones and cyclopropanes compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220422 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |