CN113200901A - Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof - Google Patents
Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof Download PDFInfo
- Publication number
- CN113200901A CN113200901A CN202110430136.6A CN202110430136A CN113200901A CN 113200901 A CN113200901 A CN 113200901A CN 202110430136 A CN202110430136 A CN 202110430136A CN 113200901 A CN113200901 A CN 113200901A
- Authority
- CN
- China
- Prior art keywords
- aryl
- phenyl
- reaction
- aziridin
- methanone
- 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.)
- Pending
Links
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000002576 ketones Chemical class 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical class OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims abstract description 35
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 16
- 150000001412 amines Chemical class 0.000 claims abstract description 8
- -1 2-fluoro-phenyl-4-fluoro-phenyl Chemical group 0.000 claims description 45
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 26
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical class O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 24
- 239000002585 base Substances 0.000 claims description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 17
- 239000012295 chemical reaction liquid Substances 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000003377 acid catalyst Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- HIYUMYXSGIKHHE-UHFFFAOYSA-M bismuth trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F HIYUMYXSGIKHHE-UHFFFAOYSA-M 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 229940125782 compound 2 Drugs 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000001095 magnesium carbonate Substances 0.000 claims description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 150000007517 lewis acids Chemical group 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 description 37
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 28
- 239000002253 acid Substances 0.000 description 18
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 13
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical group BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical class O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 5
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 5
- 229950009195 phenylpropanol Drugs 0.000 description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001503 aryl iodides Chemical class 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HFKAAIFQDJOIFH-UHFFFAOYSA-N 3-(4-bromophenyl)prop-1-yn-1-ol Chemical compound BrC1=CC=C(C=C1)CC#CO HFKAAIFQDJOIFH-UHFFFAOYSA-N 0.000 description 1
- DDOHNLJULYCMFE-UHFFFAOYSA-N 3-(4-chlorophenyl)prop-1-yn-1-ol Chemical compound OC#CCC1=CC=C(Cl)C=C1 DDOHNLJULYCMFE-UHFFFAOYSA-N 0.000 description 1
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 1
- KTJRGPZVSKWRTJ-UHFFFAOYSA-N 3-chloro-1-phenylpropan-1-one Chemical compound ClCCC(=O)C1=CC=CC=C1 KTJRGPZVSKWRTJ-UHFFFAOYSA-N 0.000 description 1
- IHWJMMVOEQXCOZ-UHFFFAOYSA-N 3-methoxyprop-1-yn-1-ol Chemical compound COCC#CO IHWJMMVOEQXCOZ-UHFFFAOYSA-N 0.000 description 1
- FSOAHWQHVGEDAI-UHFFFAOYSA-N 3-phenylprop-1-yn-1-ol Chemical compound OC#CCC1=CC=CC=C1 FSOAHWQHVGEDAI-UHFFFAOYSA-N 0.000 description 1
- HHHDJHHNEURCNV-UHFFFAOYSA-N 4-chlorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C=C1 HHHDJHHNEURCNV-UHFFFAOYSA-N 0.000 description 1
- LFLSATHZMYYIAQ-UHFFFAOYSA-N 4-flourobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C=C1 LFLSATHZMYYIAQ-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- MSFQEZBRFPAFEX-UHFFFAOYSA-N 4-methoxybenzenesulfonamide Chemical compound COC1=CC=C(S(N)(=O)=O)C=C1 MSFQEZBRFPAFEX-UHFFFAOYSA-N 0.000 description 1
- QWKKYJLAUWFPDB-UHFFFAOYSA-N 4-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 QWKKYJLAUWFPDB-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- WQZYHOKTTJAIQZ-UHFFFAOYSA-N C1=C(C=CC2=CC=CC=C12)CC#CO Chemical compound C1=C(C=CC2=CC=CC=C12)CC#CO WQZYHOKTTJAIQZ-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000006661 Meyer-Schuster rearrangement reaction Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L PdCl2(PPh3)2 Substances [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- KFJCQBLZPLAPCI-UHFFFAOYSA-N aziridin-2-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1CN1 KFJCQBLZPLAPCI-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- OSHOQERNFGVVRH-UHFFFAOYSA-K iron(3+);trifluoromethanesulfonate Chemical compound [Fe+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F OSHOQERNFGVVRH-UHFFFAOYSA-K 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/22—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
- C07D203/24—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/02—Preparation by ring-closure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/16—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms
- C07D203/18—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms by carboxylic acids, or by sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses an aziridine-2-yl- (aryl) ketone derivative and a preparation method thereof, wherein the preparation method comprises the steps of carrying out multi-step series reaction on 3-bit aryl substituted propiolic alcohol, N protected amine and N-halogenated succinimide to realize one-pot synthesis of the aziridine-2-yl- (aryl) ketone derivative. The yield of aziridine-2-yl- (aryl) ketone is 70-90%, and the method has the advantages of simple operation, mild conditions, high yield and the like, and provides a brand new synthetic method for the aziridine-2-yl- (aryl) ketone derivative.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to an aziridine-2-yl- (aryl) ketone derivative and a preparation method thereof.
Background
Aziridin-2-yl- (aryl) methanones are important Organic intermediates which can be converted into nitrogenous compounds such as tetrahydropyrrole (Organic Letters,22(6), 2470. about. 2475, 2020; Angewandte. about. International Edition 55(28), 8081. about. 8085, 2016; Chemistry Letters 33(11), 1472. about. 1473, 2004; Bull. chem. Soc. Jpn. 78, 1309. about. 1333, 2005).
ZHenhua Liu et al reported a two-step reaction for the synthesis of aziridine from 2-azidoallyl alcohol (Scheme 1, Bull. chem. Soc. Jpn.,78, 1309-1333, 2005), the azide compound in this synthesis method is extremely unstable and not easy to operate in experiments, which limits its application range.
Takuya Hashimoto starts from β -chloropropiophenone and synthesizes aziridin-2-yl- (phenyl) methanone (Angew. chem. int. Ed.2016,55, 8081-8085, Scheme 2) by a two-step conversion, which has a two-step reaction and requires the relatively expensive 4-methyl-N- (tosyloxy) benzenesulfonamide.
From the above, the reported methods for preparing aziridin-2-yl- (aryl) methanone have the disadvantages of difficult availability of reaction raw materials and high preparation cost, or the instability and difficult operation of synthesized compounds.
Disclosure of Invention
The invention aims to solve the problems and provide an aziridine-2-yl- (aryl) ketone derivative which is simple to operate and high in reaction efficiency and a preparation method thereof.
The purpose of the invention is realized by the following technical scheme:
an aziridin-2 yl- (aryl) methanone derivative, the aziridin-2 yl- (aryl) methanone derivative having a structure according to the formula:
wherein: ar is phenyl, substituted phenyl, pyridyl, naphthyl or thienyl;
r is sulfonyl or acyl.
Preferably, Ar is phenyl, 3-fluoro-phenyl, 2-fluoro-phenyl 4-fluoro-phenyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-methyl-phenyl, 4-phenyl, 4-methoxy-phenyl, 3-methoxy-phenyl, 2-naphthyl or 3-thienyl.
Preferably, R is benzenesulfonyl, 4-nitro-benzenesulfonyl, 4-methoxy-benzenesulfonyl, 4-fluoro-benzenesulfonyl, 4-chloro-benzenesulfonyl, 4-methyl-benzenesulfonyl, methanesulfonyl.
A process for the preparation of an aziridin-2-yl- (aryl) methanone derivative comprising the steps of:
(1) heating and refluxing 3 aryl-substituted propargyl alcohol, an acid catalyst and N-protected amine in a solvent, and obtaining a reaction solution containing a compound 1 after aryl-substituted propargyl alcohol completely disappears;
(2) then adding N-halogenated succinimide into the reaction liquid to obtain reaction liquid containing the compound 2;
(3) then cooling the reaction liquid to room temperature, and adding a proper amount of alkali into the reaction liquid to obtain reaction liquid containing the acyl aziridine derivative 3;
(4) extracting the reaction liquid with ethyl acetate, washing with saturated saline solution, evaporating, concentrating, and performing column separation to obtain aziridine-2-yl- (aryl) ketone derivative with purity of more than 98%;
the aryl-substituted propargyl alcohol has the structure shown below:
the N-protected amine has the structure shown below: RNH2；
The structural formula of the halogenated succinimide is as follows:
the compound 1 has the following structure:
the compound 2 has the following structure:
R1i.e. R.
The preparation method has the following chemical reaction formula:
preferably, in the step (1), the heating reflux reaction temperature in the step (1) is 105-110 ℃, the time is 1-8 h, stirring is carried out in the process, and the stirring speed is 330-340 rpm;
the acid catalyst is Lewis acid and is selected from any one of ferric trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, copper trifluoromethanesulfonate, silver trifluoromethanesulfonate and scandium trifluoromethanesulfonate; the progress of the reaction was monitored by TLC and when the aryl substituted propargyl alcohol starting material disappeared, the next step was carried out.
Preferably, in the step (1), the solvent is any one of dioxane, dichloroethane, trifluorotoluene, toluene, benzene, tetrahydrofuran or methanol;
and (3) the reaction temperature in the step (2) is 105-110 ℃, the time is 2-9 hours, stirring is carried out in the process, the stirring speed is 330-350 rpm, the reaction process is monitored by TLC, and the next step is carried out after the compound 1 in the reaction liquid disappears.
Preferably, in the step (2), the N-halogenated succinimide is NBS, NCS or NIS.
Preferably, in the step (3), the base is an organic base or an inorganic base, and is selected from any one of triethylamine, sodium hydroxide, potassium carbonate, sodium carbonate, calcium carbonate or magnesium carbonate;
and (3) the reaction temperature in the step (3) is room temperature, the time is 4-24 h, the reaction process is monitored by TLC, and the next step is carried out after the compound 2 in the reaction liquid disappears.
Preferably, the 3 aryl substituted propargyl alcohol, the N-protected amine, the N-halosuccinimide, the acid catalyst, and the base are present in a molar ratio of 1: (1.00-3.00): (1.00-2.00): (0.05-1.00): (0.50 to 2.00);
the ratio of the mole number of the 3 aryl-substituted propiolic alcohol to the volume number of the solvent is 1: 5 to 10 mol/L.
Compared with the prior art, the invention has the beneficial effects that:
the target product acyl aziridine is obtained through tandem Meyer-Schuster rearrangement reaction/intermolecular addition/alpha-halogenation reaction/cyclization reaction. The method has the advantages of easily available raw materials, simple operation, mild reaction conditions, high yield and the like. Comparing the reaction route in the literature with the reaction route, the raw materials used in the reaction are simpler and easier to obtain, and the experimental operation is more convenient and easier. The invention provides a brand-new one-pot synthesis method for synthesizing acyl aziridine.
Drawings
FIG. 1 is a photograph of the compound prepared in example 11H NMR spectrum;
FIG. 2 is a photograph of the compound prepared in example 113C NMR spectrum.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments.
The raw materials used in the examples are commercially available products, and therefore, no other contents need to be provided.
The catalyst, dioxane, dichloroethane, benzotrifluoride, toluene, benzene, tetrahydrofuran, ethyl acetate, petroleum ether, anhydrous sodium sulfate and the like used in the embodiments of the invention are all Chinese medicine reagents.
The information of the equipment and the manufacturers used in the embodiments of the present invention is as follows:
the stirrer is as follows: a Shanghai plum Yimpu MYPII-2 constant-temperature magnetic stirrer;
the circulating water pump is as follows: shanghai Yukang circulation multipurpose vacuum pump SHB-IIIA;
the rotary evaporator comprises: shanghai yukang rotary evaporator W.S 206B;
the oil pump is as follows: shanghai Yukang 2XZ-2 type rotary-vane vacuum pump;
the preparative HPLC was: shimadzu LC-20A.
The preparation method of the aryl-substituted propargyl alcohol comprises the following steps:
a round bottom flask of appropriate size was taken and charged with aryl iodide (99.8% pure, 25g per flask), PdCl2(PPh3)2CuI; then, vacuumizing the reaction bottle and protecting the reaction bottle with nitrogen, then placing the reaction bottle in an ice-water bath, slowly dropwise adding excessive propargyl alcohol (the purity is 99.9 percent and the specification is 500g per bottle) into the reaction bottle at the speed of about 5 seconds per drop, and the required dropwise adding time is about five minutes; after the dripping is finished, the reaction bottle is placed at room temperature, and is placed in an oil bath pot after the temperature of the reaction bottle is recovered to the room temperature, and the reaction is carried out at 55-60 ℃.
Monitoring the reaction by TLC, and stopping the reaction after the aryl iodide is completely reacted; quenching the reaction by using a saturated sodium bicarbonate solution, extracting by using ethyl acetate, washing by using saturated saline solution, evaporating, concentrating and carrying out column separation to obtain the aryl-substituted propargyl alcohol compound with the purity of more than 98%.
In the examples, the general preparation method of acyl aziridine specifically includes the following steps: adding aryl substituted propiolic alcohol (0.10mmol), a solvent (0.50-1.00 mL), an acid catalyst (0.005-0.1 mmol), N-protected amine (0.10-0.30 mmol) and N-halogenated succinimide (0.1-0.2 mmol) into a 10mL sealed tube in sequence, carrying out reflux reaction, then cooling to room temperature, adding a base (0.05-0.20 mmol) for reaction, monitoring the reaction by TLC, and keeping the reaction for 5-33 h.
And finally, adding water into the reaction solution to quench the reaction, adding ethyl acetate to extract an organic phase, washing the obtained organic phase with saturated sodium chloride, drying the organic phase with anhydrous sodium sulfate, concentrating the dried organic phase on a rotary evaporator, and purifying the obtained concentrated solution by column chromatography to obtain the aziridine-2-yl- (aryl) ketone.
Example 1
Phenyl (1-tosylazido-2-yl) methanones
Aryl-substituted propargyl alcohol, an amine compound, N-halogenated succinimide, an acid catalyst, a solvent, alkali species and the use amounts thereof are respectively as follows: phenyl propynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-bromosuccinimide (0.15mmol), bismuth trifluoromethanesulfonate (0.005mmol),1, 4-dioxane (0.50mL), and potassium carbonate (0.20 mmol).
Light yellow liquid；1H NMR(500MHz,Chloroform-d)δ8.05(m,2H),7.87(d,J＝10.5Hz,2H),7.62(t,J＝9.0Hz,1H),7.49(t,J＝10.0Hz,2H),7.34(d,J＝10.0Hz,2H),4.17(dd,J＝8.5,5.5Hz,1H),2.87(d,J＝8.5Hz,1H),2.74(d,J＝5.5Hz,1H),2.44(s,3H)；13C NMR(125MHz,Chloroform-d)δ191.34,145.25,135.58,134.25,134.21,129.89,128.81,128.19,37.81,32.79,21.69.IR(KBr,cm-1):3473,3287,3069,2798,1664,1489,1445,1400,1320,1231,1163,1095,1020,954,895,808,728,682,565.yield：82％.HRMS calculated for C16H16NO3S([M+H]+):302.0851；found:302.0850.
Example 2
(2-fluorophenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 2-fluoropropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：81％.HRMS calculated for C16H15FNO3S([M+H]+):320.0757；found:320.0758.
Example 3
(3-fluorophenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 3-fluoropropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), ferric triflate (0.02mmol), dichloroethane (1.0mL), and potassium carbonate (0.20 mmol).
yield：80％.HRMS calculated for C16H15FNO3S([M+H]+):320.0757；found:320.0758.
Example 4
(4-fluorophenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-fluoropropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), bismuth trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium hydroxide (0.10 mmol).
yield：81％.HRMS calculated for C16H15FNO3S([M+H]+):320.0757；found:320.0758.
Example 5
(4-chlorophenyl) (1-toluenesulfonylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-Chlorophenylpropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and triethylamine (0.20 mmol).
yield：85％.HRMS calculated for C16H15ClNO3S([M+H]+):336.0461；found:336.0460.
Example 6
(4-bromophenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-bromophenylpropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol), methanol (0.50mL), and sodium carbonate (0.20 mmol).
yield：89％.HRMS calculated for C16H15BrNO3S([M+H]+):379.9956；found:379.9955.
Example 7
P-tolyl (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-Methylbenzpropiolic alcohol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：83％.HRMS calculated for C17H18NO3S([M+H]+):316.1007；found:316.1007.
Example 8
[1, 1' -Biphenyl ] -4-yl (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-Benzenepropanol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-bromosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.1 mmol).
yield：89％.HRMS calculated for C22H20NO3S([M+H]+):378.1164；found:378.1165.
Example 9
(2-methoxyphenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 2-methoxypropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：86％.HRMS calculated for C17H18NO4S([M+H]+):332.0957；found:332.0956.
Example 10
(3-methoxyphenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 3-methoxypropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：87％.HRMS calculated for C17H18NO4S([M+H]+):320.0757；found:320.0758.
Example 11
(4-methoxyphenyl) (1-tosylazido-2-yl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 4-methoxypropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：89％.HRMS calculated for C17H18NO4S([M+H]+):332.0957；found:332.0958.
Example 12
Naphthalen-2-yl (1-tosylazido-2-yl) methanones
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 2-Naphthylpropynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-bromosuccinimide (0.1mmol), bismuth trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：87％.HRMS calculated for C20H17NO3S([M+H]+):352.1007；found:352.1007.
Example 13
Thien-2-yl (1-tosylazido-2-yl) methanones
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: 2-thiophenylbenzynol (0.10mmol), p-methylbenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：81％.HRMS calculated for C14H14NO3S2([M+H]+):308.0415；found:308.0415.
Example 14
Phenyl (1- (phenylsulfonyl) azido-2-yl) methanones
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenylpropanol (0.10mmol), benzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：88％.HRMS calculated for C15H14NO3S([M+H]+):288.0694；found:288.0695.
Example 15
(1- ((4-nitrophenyl) sulfonyl) azido-2-yl) (phenyl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenylpropanol (0.10mmol), p-nitrobenzenesulfonamide (0.12mmol), N-chlorosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium carbonate (0.20 mmol).
yield：72％.HRMS calculated for C15H13N2O5S([M+H]+):333.0545；found:333.0546.
Example 16
(1- ((4-methoxyphenyl) sulfonyl) azido-2-yl) (phenyl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenylpropanol (0.10mmol), p-methoxybenzenesulfonamide (0.12mmol), N-iodosuccinimide (0.15mmol), copper trifluoromethanesulfonate (0.02mmol),1, 4-dioxane (0.50mL), and sodium hydroxide (0.20 mmol).
yield：90％.HRMS calculated for C16H16NO4S([M+H]+):318.0800；found:318.0801.
Example 17
((1- ((4-chlorophenyl) sulfonyl) azido-2-yl) (phenyl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenylpropanol (0.10mmol), p-chlorobenzenesulfonamide (0.15mmol), N-iodosuccinimide (0.2mmol), scandium trifluoromethanesulfonate (0.02mmol), toluene (0.50mL), and magnesium carbonate (0.20 mmol).
yield：76％.HRMS calculated for C15H13ClNO3S([M+H]+):322.0305；found:322.0306.
Example 18
(1- ((4-fluorophenyl) sulfonyl) azido-2-yl) (phenyl) methanone
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenyl propiolic alcohol (0.10mmol), p-fluorobenzenesulfonamide (0.3mmol), N-chlorosuccinimide (0.1mmol), silver triflate (0.06mmol), trifluorotoluene (0.50mL), and calcium carbonate (0.20 mmol).
yield：79％.HRMS calculated for C15H13FNO3S([M+H]+):306.0600；found:306.0601.
Example 19
Aziridine-1, 2-diylbis (benzophenone)
The aryl-substituted propargyl alcohol, the amine compound, the N-halogenated succinimide, the catalyst acid, the solvent, the catalyst base and the dosage thereof are respectively as follows: phenylpropanol (0.10mmol), benzamide (0.12mmol), N-bromosuccinimide (0.15mmol), bismuth trifluoromethanesulfonate (0.1mmol),1, 2-dichloroethane (1.0mL), and potassium hydroxide (0.30 mmol).
yield：70％.HRMS calculated for C16H14NO2([M+H]+):252.1025；found:252.1026.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. An aziridin-2 yl- (aryl) methanone derivative, characterized in that the aziridin-2 yl- (aryl) methanone derivative has the structure shown in the following formula:
wherein: ar is phenyl, substituted phenyl, pyridyl, naphthyl or thienyl;
r is sulfonyl or acyl.
2. An aziridin-2 yl- (aryl) methanone derivative according to claim 1, characterised in that Ar is phenyl, 3-fluoro-phenyl, 2-fluoro-phenyl-4-fluoro-phenyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-methyl-phenyl, 4-phenyl, 4-methoxy-phenyl, 3-methoxy-phenyl, 2-naphthyl or 3-thienyl.
3. The aziridin-2 yl- (aryl) methanone derivative of claim 1, wherein R is benzenesulfonyl, 4-nitro-benzenesulfonyl, 4-methoxy-benzenesulfonyl, 4-fluoro-benzenesulfonyl, 4-chloro-benzenesulfonyl, 4-methyl-benzenesulfonyl, methanesulfonyl.
4. A process for the preparation of an aziridin-2 yl- (aryl) methanone derivative according to any of claims 1 to 3, comprising the steps of:
(1) heating and refluxing 3 aryl-substituted propargyl alcohol, an acid catalyst and N-protected amine in a solvent, and obtaining a reaction solution containing a compound 1 after aryl-substituted propargyl alcohol completely disappears;
(2) then adding N-halogenated succinimide into the reaction liquid to obtain reaction liquid containing the compound 2;
(3) then cooling the reaction liquid to room temperature, and adding a proper amount of alkali into the reaction liquid to obtain reaction liquid containing the acyl aziridine derivative 3;
(4) extracting the reaction liquid with ethyl acetate, washing with saturated saline solution, evaporating, concentrating, and performing column separation to obtain aziridine-2-yl- (aryl) ketone derivative with purity of more than 98%;
the aryl-substituted propargyl alcohol has the structure shown below:
the N-protected amine has the structure shown below: RNH2；
The compound 1 has the following structure:
the compound 2 has the following structure:
5. the method of claim 4, wherein the aziridin-2-yl- (aryl) methanone derivative is prepared according to the following reaction scheme:
6. the method for preparing aziridin-2 yl- (aryl) methanone according to claim 4, wherein in the step (1), the heating reflux reaction temperature in the step (1) is 105-110 ℃, the time is 1-8 h, and the process is performed with stirring at 330-340 rpm;
the acid catalyst is Lewis acid and is selected from any one of ferric trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, copper trifluoromethanesulfonate, silver trifluoromethanesulfonate and scandium trifluoromethanesulfonate; the progress of the reaction was monitored by TLC and when the aryl substituted propargyl alcohol starting material disappeared, the next step was carried out.
7. The method for preparing an aziridin-2 yl- (aryl) methanone derivative according to claim 4, wherein in the step (1), the solvent is any one of dioxane, dichloroethane, trifluorotoluene, toluene, benzene, tetrahydrofuran, or methanol;
and (3) the reaction temperature in the step (2) is 105-110 ℃, the time is 2-9 hours, stirring is carried out in the process, the stirring speed is 330-350 rpm, the reaction process is monitored by TLC, and the next step is carried out after the compound 1 in the reaction liquid disappears.
8. The method for preparing an aziridin-2 yl- (aryl) methanone derivative according to claim 4, wherein in the step (2), the N-halosuccinimide is NBS, NCS, NIS.
9. The method for preparing an aziridin-2 yl- (aryl) methanone derivative according to claim 4, wherein in the step (3), the base is an organic or inorganic base selected from any one of triethylamine, sodium hydroxide, potassium carbonate, sodium carbonate, calcium carbonate or magnesium carbonate;
and (3) the reaction temperature in the step (3) is room temperature, the time is 4-24 h, the reaction process is monitored by TLC, and the next step is carried out after the compound 2 in the reaction liquid disappears.
10. The method of claim 4, wherein the molar ratio of 3 aryl substituted propiolic alcohol, N protected amine, N-halosuccinimide, acid catalyst and base is 1: (1.00-3.00): (1.00-2.00): (0.05-1.00): (0.50 to 2.00);
the ratio of the mole number of the 3 aryl-substituted propiolic alcohol to the volume number of the solvent is 1: 5 to 10 mol/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110430136.6A CN113200901A (en) | 2021-04-21 | 2021-04-21 | Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110430136.6A CN113200901A (en) | 2021-04-21 | 2021-04-21 | Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113200901A true CN113200901A (en) | 2021-08-03 |
Family
ID=77027529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110430136.6A Pending CN113200901A (en) | 2021-04-21 | 2021-04-21 | Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113200901A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107698469A (en) * | 2017-10-13 | 2018-02-16 | 上海应用技术大学 | A kind of preparation method of α halos β amino ketones |
-
2021
- 2021-04-21 CN CN202110430136.6A patent/CN113200901A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107698469A (en) * | 2017-10-13 | 2018-02-16 | 上海应用技术大学 | A kind of preparation method of α halos β amino ketones |
Non-Patent Citations (1)
| Title |
|---|
| WEI JUNFA ET AL.: "A Rapid and Simple Method for Quantitative Aziridination frOm Am inobrominated Derivatives of Olefins under Solvent-free and Mild Conditions", 《CHIN.J.CHEM．》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107698469B (en) | Preparation method of alpha-halogenated-beta-aminoketone | |
| Li et al. | One-pot, highly efficient, asymmetric synthesis of ring-fused piperidine derivatives bearing N, O-or N, N-acetal moieties | |
| Griffiths-Jones et al. | Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination | |
| CN111646990A (en) | Preparation method of 3, 4-bridged ring indole compound and synthesis method of Rucaparib | |
| Kerr et al. | Enantioselective N-heterocyclic carbene catalyzed formal [3+ 2] cycloaddition using α-aroyloxyaldehydes and oxaziridines | |
| US5196607A (en) | Process for preparing ketone enantiomer | |
| CN113200901A (en) | Aziridine-2-yl- (aryl) ketone derivative and preparation method thereof | |
| CN106977386B (en) | 2-trifluoroethyl-1-indanone and derivatives and preparation method thereof | |
| Boultwood et al. | Studies on the synthesis of α-iodoaziridines and improved conditions for the synthesis of alkyl-α-iodoaziridines using ClMgCHI2 | |
| Olofson et al. | An efficient synthesis of enol carbonates | |
| CN116478022A (en) | Preparation method of alkynylamide-mediated ketone compound | |
| TOYOTA et al. | α-Fluorination of Methyl Phenyl Sulfoxide and Rlated Compounds by Molecular Fluorine; A Novel Method for the Introduction of Fluorine into Sulfoxides Bearing α-H Atoms | |
| CN110467514B (en) | Preparation method of alpha-halogenated unsaturated aldehyde ketone | |
| CN113264865A (en) | 2-amino-4-benzoyl-4, 5-dihydro-1H-pyrrole-3-carbon nitrile and preparation method thereof | |
| JP3937489B2 (en) | Method for producing propargylamine compound | |
| Kim et al. | A mild procedure for the stereospecific transformation of trans cinnamic acid derivatives to cis β-bromostyrenes | |
| CN113200915A (en) | 3-aryl-4, 5-dihydro-1H-pyrazole-5 amine and preparation method thereof | |
| CN110183456A (en) | A kind of synthetic method of 2- arylindazoles succinimide spiro-compound | |
| CN113214183A (en) | 5- (aminomethyl) -4-arylthiophene-2-amine derivative and preparation method thereof | |
| CN113896647B (en) | Synthesis method of tertiary amide | |
| EP1023283B1 (en) | Synthesis of 3-carbomethoxy-4,5-dimethylthiophene | |
| Hu et al. | A Synthetic Method for Diselenides Under Phase-Transfer Conditions | |
| CN113004321B (en) | Method for desymmetrizing 3-substituted cyclobutanone, cyclobutene compound and application thereof | |
| CN112321398B (en) | Method for synthesizing alpha-fluorinated ketone by hydrazonating aliphatic chain monoketone | |
| CN110256247B (en) | Synthesis method of 2- ((9-hydrofluoren-9-yl) methyl) malonate |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210803 |
|
| RJ01 | Rejection of invention patent application after publication |