CN103333171A - Synthetic method of pyrrole [1,2-a ] quinoxaline derivative - Google Patents
Synthetic method of pyrrole [1,2-a ] quinoxaline derivative Download PDFInfo
- Publication number
- CN103333171A CN103333171A CN2013102383032A CN201310238303A CN103333171A CN 103333171 A CN103333171 A CN 103333171A CN 2013102383032 A CN2013102383032 A CN 2013102383032A CN 201310238303 A CN201310238303 A CN 201310238303A CN 103333171 A CN103333171 A CN 103333171A
- Authority
- CN
- China
- Prior art keywords
- tetralyl
- formaldehyde
- phenyl
- pyrroles
- quinoxaline
- 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 13
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title abstract 8
- 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 78
- -1 2-formyl azole compound Chemical class 0.000 claims abstract description 49
- 239000002994 raw material Substances 0.000 claims abstract description 34
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 5
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 240
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 67
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 61
- 150000003233 pyrroles Chemical class 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 239000011630 iodine Substances 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 239000011737 fluorine Substances 0.000 claims description 14
- 150000003252 quinoxalines Chemical class 0.000 claims description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- 229910052786 argon Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- UOHBMRODJBFDPN-UHFFFAOYSA-N C(C)(C)(C)O.[Li] Chemical compound C(C)(C)(C)O.[Li] UOHBMRODJBFDPN-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- PNWSHHILERSSLF-UHFFFAOYSA-N 4-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=C1C(O)=O PNWSHHILERSSLF-UHFFFAOYSA-N 0.000 claims description 2
- PMZBHPUNQNKBOA-UHFFFAOYSA-N 5-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(C(O)=O)=C1 PMZBHPUNQNKBOA-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 239000004914 cyclooctane Substances 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000001035 drying Methods 0.000 abstract description 34
- 238000001816 cooling Methods 0.000 abstract description 33
- 238000002360 preparation method Methods 0.000 abstract description 32
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical class O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 abstract description 31
- 238000000034 method Methods 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 150000003624 transition metals Chemical class 0.000 abstract description 3
- 238000003756 stirring Methods 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 238000003912 environmental pollution Methods 0.000 abstract 1
- 150000002736 metal compounds Chemical class 0.000 abstract 1
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 230
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 122
- UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical compound NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 36
- 238000004821 distillation Methods 0.000 description 33
- 238000000605 extraction Methods 0.000 description 33
- 238000001953 recrystallisation Methods 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- 238000005406 washing Methods 0.000 description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 31
- 238000001819 mass spectrum Methods 0.000 description 31
- 238000001228 spectrum Methods 0.000 description 31
- 150000003254 radicals Chemical class 0.000 description 30
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical class C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 4
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical class CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- 150000002475 indoles Chemical class 0.000 description 4
- 229940074386 skatole Drugs 0.000 description 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 3
- 0 *C(C(N)=*)=*C(I)=* Chemical compound *C(C(N)=*)=*C(I)=* 0.000 description 3
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 3
- MRLVFVTVXSKAMX-UHFFFAOYSA-N Methyl 4-amino-3-iodobenzoate Chemical class COC(=O)C1=CC=C(N)C(I)=C1 MRLVFVTVXSKAMX-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- NEOLWKPYXMBCON-UHFFFAOYSA-N n-fluoro-2-iodoaniline Chemical compound FNC1=CC=CC=C1I NEOLWKPYXMBCON-UHFFFAOYSA-N 0.000 description 3
- CTWQGTOWGFCWNW-UHFFFAOYSA-N 1,3-dimethylpyrrole Chemical class CC=1C=CN(C)C=1 CTWQGTOWGFCWNW-UHFFFAOYSA-N 0.000 description 2
- UQNRTIQURQZGKL-UHFFFAOYSA-N 1-(2-nitrophenyl)pyrrole Chemical class [O-][N+](=O)C1=CC=CC=C1N1C=CC=C1 UQNRTIQURQZGKL-UHFFFAOYSA-N 0.000 description 2
- 150000005356 1-phenylpyrroles Chemical class 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- GDMZHPUPLWQIBD-UHFFFAOYSA-N 2-pyrrol-1-ylaniline Chemical class NC1=CC=CC=C1N1C=CC=C1 GDMZHPUPLWQIBD-UHFFFAOYSA-N 0.000 description 2
- AWLDDDPIAFHCFV-UHFFFAOYSA-N 5-phenyl-1h-pyrrole-2-carbaldehyde Chemical class N1C(C=O)=CC=C1C1=CC=CC=C1 AWLDDDPIAFHCFV-UHFFFAOYSA-N 0.000 description 2
- GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical group CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- IEOUSWADWJLLCH-UHFFFAOYSA-N c1c[n]2c3ccccc3ncc2c1 Chemical compound c1c[n]2c3ccccc3ncc2c1 IEOUSWADWJLLCH-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 2
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- LMLICLRBZPFXMK-UHFFFAOYSA-N 1-(2-nitrophenyl)pyrrole-2-carbaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1N1C(C=O)=CC=C1 LMLICLRBZPFXMK-UHFFFAOYSA-N 0.000 description 1
- ZLKHNURELCONBB-UHFFFAOYSA-N 2,5-diethoxyoxolane Chemical compound CCOC1CCC(OCC)O1 ZLKHNURELCONBB-UHFFFAOYSA-N 0.000 description 1
- HERGPIKZUJHAPU-UHFFFAOYSA-N 2-bromo-n-fluoroaniline Chemical compound FNC1=CC=CC=C1Br HERGPIKZUJHAPU-UHFFFAOYSA-N 0.000 description 1
- MMWNKXIFVYQOTK-UHFFFAOYSA-N 2-bromopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Br MMWNKXIFVYQOTK-UHFFFAOYSA-N 0.000 description 1
- WZNXAIBXIRFTOU-UHFFFAOYSA-N 2-chloro-n-fluoroaniline Chemical compound FNC1=CC=CC=C1Cl WZNXAIBXIRFTOU-UHFFFAOYSA-N 0.000 description 1
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 1
- KEYRTRGLKSAGJN-UHFFFAOYSA-N 2-iodopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1I KEYRTRGLKSAGJN-UHFFFAOYSA-N 0.000 description 1
- ZCTJXWVTLAHGAJ-UHFFFAOYSA-N 2-pyrrol-1-ylbenzonitrile Chemical compound N#CC1=CC=CC=C1N1C=CC=C1 ZCTJXWVTLAHGAJ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CLNMDAHACQMSLK-UHFFFAOYSA-N 4-amino-2-bromo-3-methylbenzoic acid Chemical compound CC1=C(N)C=CC(C(O)=O)=C1Br CLNMDAHACQMSLK-UHFFFAOYSA-N 0.000 description 1
- RHJLTOVSJKKHLY-UHFFFAOYSA-N 4-bromo-2-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=NC=CC(Br)=N1 RHJLTOVSJKKHLY-UHFFFAOYSA-N 0.000 description 1
- OVEGSCLVOXWLIV-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=NC=CC(Cl)=N1 OVEGSCLVOXWLIV-UHFFFAOYSA-N 0.000 description 1
- FOUBPRFOENCSCV-UHFFFAOYSA-N 4-iodo-2-(trifluoromethyl)pyrimidine Chemical compound C1=CC(I)=NC(=N1)C(F)(F)F FOUBPRFOENCSCV-UHFFFAOYSA-N 0.000 description 1
- 229930008564 C01BA04 - Sparteine Natural products 0.000 description 1
- YJCDFRYWKULQAL-AATRIKPKSA-N C=C/C=C(/C(F)(F)F)\C=C Chemical compound C=C/C=C(/C(F)(F)F)\C=C YJCDFRYWKULQAL-AATRIKPKSA-N 0.000 description 1
- ZBVIQJJUYVNJFV-UHFFFAOYSA-N COc(cc1)cc2c1[n]1c(cccc3)c3ncc1c2 Chemical compound COc(cc1)cc2c1[n]1c(cccc3)c3ncc1c2 ZBVIQJJUYVNJFV-UHFFFAOYSA-N 0.000 description 1
- IEHXXJMABHGXCG-UHFFFAOYSA-N COc1ccc2[nH]c(C=O)cc2c1 Chemical compound COc1ccc2[nH]c(C=O)cc2c1 IEHXXJMABHGXCG-UHFFFAOYSA-N 0.000 description 1
- AJTUKWIQLKKRHE-UHFFFAOYSA-N Cc(cc1)cc(I)c1N Chemical compound Cc(cc1)cc(I)c1N AJTUKWIQLKKRHE-UHFFFAOYSA-N 0.000 description 1
- PAXQXJDYVORMOO-UHFFFAOYSA-N Cc1cc(C(F)(F)F)ccc1N Chemical compound Cc1cc(C(F)(F)F)ccc1N PAXQXJDYVORMOO-UHFFFAOYSA-N 0.000 description 1
- BMWNARUQLPHITF-UHFFFAOYSA-N Cc1cccc-2c1CCc1c-2cc(C=O)[nH]1 Chemical compound Cc1cccc-2c1CCc1c-2cc(C=O)[nH]1 BMWNARUQLPHITF-UHFFFAOYSA-N 0.000 description 1
- RNVCVTLRINQCPJ-UHFFFAOYSA-N Cc1ccccc1N Chemical compound Cc1ccccc1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 1
- DQNDDUOCVSWTOW-UHFFFAOYSA-N Cc1ncncc1N Chemical compound Cc1ncncc1N DQNDDUOCVSWTOW-UHFFFAOYSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- RUHKUUFAKLLDEY-UHFFFAOYSA-N FC(C1=CC=CC=C1)(F)F.[Br] Chemical compound FC(C1=CC=CC=C1)(F)F.[Br] RUHKUUFAKLLDEY-UHFFFAOYSA-N 0.000 description 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 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- UKKWTZPXYIYONW-UHFFFAOYSA-N Nc1ccc(C(F)(F)F)cc1I Chemical compound Nc1ccc(C(F)(F)F)cc1I UKKWTZPXYIYONW-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- SLRCCWJSBJZJBV-UHFFFAOYSA-N alpha-isosparteine Natural products C1N2CCCCC2C2CN3CCCCC3C1C2 SLRCCWJSBJZJBV-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229960001238 methylnicotinate Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- YAVXLTMRALFZIS-UHFFFAOYSA-N piperidine-2-carbonitrile Chemical compound N#CC1CCCCN1 YAVXLTMRALFZIS-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- SLRCCWJSBJZJBV-AJNGGQMLSA-N sparteine Chemical compound C1N2CCCC[C@H]2[C@@H]2CN3CCCC[C@H]3[C@H]1C2 SLRCCWJSBJZJBV-AJNGGQMLSA-N 0.000 description 1
- 229960001945 sparteine Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
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Abstract
The invention relates to a synthetic method of a pyrrole [1,2-a ] quinoxaline derivative, belonging to the technical field of chemical preparation. Taking 2-halogen arylamine and 2-formyl azole compounds as raw materials, wherein the mass ratio of the 2-halogen arylamine to the 2-formyl azole compounds is 1-3: dissolving a 2-formyl azole compound and 2-halogen arylamine in an organic solvent, adding an alkaline medium, stirring for 12-24 hours at 80-100 ℃ under the protection of inert gas to react to obtain a pyrrole [1,2-a ] quinoxaline derivative, and cooling, extracting, drying and distilling under reduced pressure to obtain a pure product. The method for synthesizing the pyrrole [1,2-a ] quinoxaline derivative has the following beneficial effects: the reaction condition is mild, the catalytic activity is high, the reaction yield is up to more than 90 percent and can reach 100 percent at most, the product selectivity is high, and the substrate expansion range is wide. (2) The catalytic system avoids the use of transition metals, especially noble metal compounds, and has the advantages of low cost, safety, convenience and little environmental pollution caused by the reaction system.
Description
Technical field
The present invention relates to the organic synthesis field, be specifically related to the synthetic method of a kind of pyrroles [1,2-a] quinoxaline derivatives.
Background technology
The pyrroles [1,2-a] quinoxaline derivatives is a kind of important benzopyrazines heterocyclic compounds, there is higher thermostability and electron affinity energy, quinoxaline compounds, because its inner distinctive molecular conjugation structure is many important skeletons that the important biomolecule active compound is arranged, also is widely used in fluorescence probe material simultaneously.The method of traditional synthetic pyrroles [1,2-a] quinoxaline is through two steps: at first by aryl 1,2-diamine compounds and 2,5-diethoxy tetrahydrofuran (THF) generate 1-2-aminophenyl pyrroles under the condition of heating, then add formic acid,
Reflux 10～13h obtains product, and productive rate is 28%(Cheeseman et al.Chem.Ind, and 1965,1382.).
In recent years, the method for synthetic pyrroles [1,2-a] quinoxaline that many bibliographical informations arranged: such as people such as Kobayashi, reported and used BF
3(OEt
2) catalysis 1-2-Cyanophenylpyrrole and alkane ketone under the existence of methylene dichloride, 0 ℃ of reaction obtain pyrroles [1,2-a] quinoxaline derivatives (Kobayashi et al.Chem.Lett, 1998,551-552.); Harrak has reported that in 2007 1-2-nitrophenyl pyrroles is at phosphorus oxychloride and N, under the existence of dinethylformamide, reaction first generates 1-2-nitrophenyl-1H-pyrrole-2-aldehyde, then obtain pyrroles [1 through intramolecular C-N linked reaction, 2-a] quinoxaline (Harrak et al.Arkivoc, 2007,4,251-259.); Jonathan at 2009 annual reports by pyrrole-2-aldehyde and 2-Iodoaniline at CuI, K
3pO
4, NMP and sparteine catalysis under, 130 ℃ are stirred 24h and obtain pyrroles [1,2-a] quinoxaline derivatives (Jonathan T.Reeves, J.Org.Chem.2010,75,992 – 994.); Use AlCl
3/ BtH/THF mixed solvent catalysis 1-2-aminophenyl pyrrole derivative and corresponding aldehyde stir at normal temperatures 1～2h obtain pyrroles [1,2-a] quinoxaline derivatives (Akhilesh et al.Eur.J.Org.Chem, 2011,4,6998-7010.); Maria in 2012 reported 1-2-nitrophenyl pyrroles with corresponding alcohol under the existence of fe and hydrochloric acid, in air, reflux obtain pyrroles [1,2-a] quinoxaline derivatives (Maria et al.Org.Lett, 2012,4,251-259.).
But, above-mentioned the whole bag of tricks all exists some defects, reactions steps is more loaded down with trivial details, condition is harsher, productive rate is lower, aftertreatment is more difficult, need complicated part, use some virose solvents, especially use some transition-metal catalysts, fancy price, stronger toxicity and the dependence of high toxicity phosphorus-containing ligand has seriously been restricted to its industrial applications in a lot of fields.
Summary of the invention
The objective of the invention is to provide in order to improve the deficiencies in the prior art a kind of pyrroles [1,2-a] synthetic method of quinoxaline derivatives.The method is low-cost, without transition metal-catalyzed, productive rate is high, the substrate suitability is wide.
The technical solution used in the present invention is: the synthetic method of a kind of pyrroles [1,2-a] quinoxaline derivatives, take 2-halogen arylamine and 2-formyl radical azole compounds as synthetic pyrroles [1, the 2-a] quinoxaline derivatives of reactant: specifically comprise the following steps:
By 2-halogen arylamine, with 2-formyl radical azole compounds amount of substance ratio, be 1～3:1, get 2-halogen arylamine and 2-formyl radical azole compounds is dissolved in organic solvent, add alkaline medium, under protection of inert gas, 80～100 ℃ are stirred reaction in 12～24 hours and obtain pyrroles [1,2-a] quinoxaline derivatives;
Reaction process is as follows:
The structural formula of preferred described 2-halogen arylamine is as follows:
2-halogen arylamine is selected from: the 2-Iodoaniline
The 2-bromaniline
The 2-chloroaniline
2-amino-3-iodine pyridine
2-amino-3-bromopyridine
2-amino-3-chloropyridine
5-amino-4-iodine pyrimidine
5-amino-4-bromo pyrimi piperidine
5-amino-4-chlorine pyrimidine
4-amino-3-iodine benzotrifluoride
4-amino-3-ioxynil
4-amino-3-iodo-benzoic acid methyl esters
The fluoro-2-Iodoaniline of 5-
4-amino-3-5 bromine benzotrifluoride
4-amino-3-Brominal
4-amino-3-methyl-bromobenzoate
The fluoro-2-bromaniline of 5-
4-amino-3-chlorobenzotrifluoride
4-amino-3-6-chlorophenyl nitrile
4-amino-3-chloro benzoic ether
The fluoro-2-chloroaniline of 5-
The iodo-5-5-flumethiazine of 2-amino-3-
The iodo-nicotinic acid nitrile of 6-amino-5-
6-amino-5-iodine methyl nicotinate
The fluoro-3-iodine pyridine of 6--2-amine
The bromo-2-chlorin-5-trifluoro picoline of 3-
The bromo-nicotinic acid nitrile of 6-amino-5-
6-amino-5-bromo-nicotinic acid methyl esters
The bromo-6-fluorine pyridine of 3--2-amine
The 2-amido-3-5-trifluoro picoline
The chloro-nicotinic acid nitrile of 6-amino-5-
6-amino-5-chlorine apellagrin methyl esters
The chloro-6-fluorine pyridine of 3--2-amine
The iodo-2-trifluoromethyl pyrimidine of 4--5-amine
The bromo-2-trifluoromethyl pyrimidine of 4--5-amine
The chloro-2-trifluoromethyl pyrimidine of 4--5-amine
5-amido-4-iodine pyrimidine-2-nitrile
5-amido-4-bromo pyrimi piperidine-2-nitrile
5-amido-4-chlorine pyrimidine-2-nitrile
Methyl 5-amido-4 chlorine pyrimidine-2-carboxyl
Methyl 5-amido-4 bromo pyrimi piperidines-2-carboxyl
Methyl 5-amido-4 iodine pyrimidines-2-carboxyl
The fluoro-4-iodine pyrimidine of 2--5-amido
The fluoro-4-bromo pyrimi piperidine of 2--5-amido
Or the fluoro-4-chlorine pyrimidine of 2--5-amido
In a kind of.
The structural formula of preferred described 2-formyl radical azole compounds is as follows:
2-formoxyl azole compounds is selected from: pyrrole-2-aldehyde
Imidazoles-2-formaldehyde
Pyrazoles-2-formaldehyde
3,5-dimethyl-2-pyrrole aldehyde
3-methyl-pyrazoles-5-formaldehyde
4-methyl-imidazoles-2-formaldehyde
5-phenyl-pyrrole-2-aldehyde
4-phenyl-pyrrole-2-aldehyde
3-phenyl-pyrrole-2-aldehyde
Indoles-2 formaldehyde
4-methyl-indoles-2 formaldehyde
5-methyl-indoles-2 formaldehyde
6-methyl-indoles-2 formaldehyde
7-methyl-indoles-2 formaldehyde
4-methoxyl group-indoles-2 formaldehyde
5-methoxyl group-indoles-2 formaldehyde
6-methoxyl group-indoles-2 formaldehyde
7-methoxyl group-indoles-2 formaldehyde
4-is fluorine-based-indoles-2 formaldehyde
5-is fluorine-based-indoles-2 formaldehyde
6-is fluorine-based-indoles-2 formaldehyde
7-is fluorine-based-indoles-2 formaldehyde
4-chloro-indoles-2 formaldehyde
5-chloro-indoles-2 formaldehyde
6-chloro-indoles-2 formaldehyde
7-chloro-indoles-2 formaldehyde
4-bromo-indoles-2 formaldehyde
5-bromo-indoles-2 formaldehyde
6-bromo-indoles-2 formaldehyde
7-bromo-indoles-2 formaldehyde
4-iodo-indoles-2 formaldehyde
5-iodo-indoles-2 formaldehyde
6-iodo-indoles-2 formaldehyde
7-iodo-indoles-2 formaldehyde
4-nitro-indoles-2 formaldehyde
5-nitro-indoles-2 formaldehyde
6-nitro-indoles-2 formaldehyde
7-nitro-indoles-2 formaldehyde
Benzimidazolyl-2 radicals formaldehyde
4-nitro-benzimidazolyl-2 radicals formaldehyde
5-nitro-benzimidazolyl-2 radicals formaldehyde
6-nitro-benzimidazolyl-2 radicals formaldehyde
4-iodo-benzimidazolyl-2 radicals formaldehyde
5-iodo-benzimidazolyl-2 radicals formaldehyde
6-iodo-benzimidazolyl-2 radicals formaldehyde
7-iodo-benzimidazolyl-2 radicals formaldehyde
4-bromo-benzimidazolyl-2 radicals formaldehyde
5-bromo-benzimidazolyl-2 radicals formaldehyde
6-bromo-benzimidazolyl-2 radicals formaldehyde
7-bromo-benzimidazolyl-2 radicals formaldehyde
4-chloro-benzimidazolyl-2 radicals formaldehyde
5-chloro-benzimidazolyl-2 radicals formaldehyde
6-chloro-benzimidazolyl-2 radicals formaldehyde
7-chloro-benzimidazolyl-2 radicals formaldehyde
4-is fluorine-based-benzimidazolyl-2 radicals formaldehyde
5-is fluorine-based-benzimidazolyl-2 radicals formaldehyde
6-is fluorine-based-benzimidazolyl-2 radicals formaldehyde
7-is fluorine-based-benzimidazolyl-2 radicals formaldehyde
4-methyl-benzimidazolyl-2 radicals formaldehyde
5-methyl-benzimidazolyl-2 radicals formaldehyde
6-methyl-benzimidazolyl-2 radicals formaldehyde
7-methyl-benzimidazolyl-2 radicals formaldehyde
4-methoxyl group-benzimidazolyl-2 radicals formaldehyde
5-methoxyl group-benzimidazolyl-2 radicals formaldehyde
6-methoxyl group-benzimidazolyl-2 radicals formaldehyde
7-methoxyl group-benzimidazolyl-2 radicals formaldehyde
4,5-dihydro-benzindole-2-formaldehyde
6-methyl-4,5-dihydro-benzindole-2-formaldehyde
7-methyl-4,5-dihydro-benzindole-2-formaldehyde
8-methyl-4,5-dihydro-benzindole-2-formaldehyde
9-methyl-4,5-dihydro-benzindole-2-formaldehyde
6-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde
7-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde
8-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde
9-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde
Or 4,5,6,7,8,9-hexahydro-1H-cyclooctane-pyrrole-2-aldehyde
In a kind of.
Described alkaline medium is trimethyl carbinol metal-salt or hydroxide radical metal-salt, and molecular formula is (CH
3)
3cOM and M (OH), wherein metal M is selected from lithium (Li), sodium (Na), potassium (K); A kind of in trimethyl carbinol lithium, sodium tert-butoxide, potassium tert.-butoxide, lithium hydroxide or sodium hydroxide more preferably; Preferably alkaline medium and 2-formyl radical azole compounds amount of substance ratio are 1～3:1.
Preferred described organic solvent is a kind of in dimethyl sulfoxide (DMSO), dimethyl formamide (DMF) or toluene.The amount of organic solvent is that the solubilizing reaction raw material gets final product.
Preferred described inert nitrogen gas or argon gas.
In technique scheme, reaction needs inert nitrogen gas or argon shield, and 80～100 ℃ are stirred end in 12～24 hours, and system obtains product through cooling, extraction, drying, underpressure distillation, after recrystallization, can obtain highly purified product.
Due to the utilization of technique scheme, the present invention compared with prior art has following advantages:
1. due to alkaline medium, and the application of reactant 2-formyl radical azole compounds and 2-halogen arylamine, this reaction can be carried out at lower temperature, and reaction conditions is simple, gentleness, and reaction yield is high, can reach 100% productive rate.
2. take trimethyl carbinol metal-salt or hydroxide radical metal-salt is alkaline medium, and reaction system only need add organic solvent just can obtain target product, has solved the increase of final product Financial cost and the problem that transition metal may be residual, has reduced the pollution to environment; Product can complete aftertreatment through overcooling, extraction, drying, underpressure distillation, washing, recrystallization, and aftertreatment is simple, convenient.
3. above-mentioned set up catalyst system, suitability is extensive, and the transformation efficiency of substrate and the productive rate of product are all very high, have expanded the industrial applications in a lot of fields.
Embodiment
Below in conjunction with embodiment, the invention will be further described, but embodiment does not limit the present invention in any way:
Embodiment 1:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 2:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), argon shield, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 3:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.43mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 4:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.645mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 5:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium hydroxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol sodium hydroxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 87%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 6:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol trimethyl carbinol lithium; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 83%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 7:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl formamide (DMF) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again 1.5ml dimethyl formamide (DMF), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 76%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 8:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, toluene is raw material, and its reaction formula is as follows:
The preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, the 0.54mmol potassium tert.-butoxide, then add 1.5ml toluene, and nitrogen protection, 100 ℃ are stirred 24 hours, and solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 56%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 9:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.215mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 50%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 10:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.645mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 11:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 80 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 65%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 12:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 12 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 51%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 13:
The present embodiment be imidazoles [1,2-a] quinoxaline synthetic to take 2-bromaniline, imidazoles-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) be raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol imidazoles-2-formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-bromaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 91%, this imidazoles [1,2-a] quinoxaline fusing point is 124-126 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3); δ 9.13 (s, 1H), 8.15-8.13 (m, 2H), 7.93-7.91 (m, 1H), 7.83 (s, 1H), 7.70-7.66 (m, 1H), 7.63-7.59 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
10h
8n
3(M
*) 170.0712, found:170.0724.
Embodiment 14:
The present embodiment is the synthetic of pyrroles [1,2-a] quinoxaline, and take 2-chloroaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-chloroaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 53%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s, 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m, 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
9n
2(M
*) 169.0760, found:169.0769.
Embodiment 15:
The present embodiment is the synthetic of 1,3-dimethyl-pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, 3,5-dimethyl-2-pyrrole aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) are raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 3 in the 25ml eggplant-shape bottle, 5-dimethyl-2-pyrrole aldehyde, 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide, then add 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection; 100 ℃ are stirred 24 hours, and solution colour becomes transparent color, have product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 92%, this 1,3-dimethyl-pyrroles [1,2-a] quinoxaline fusing point is 65-69 ℃; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3); δ 8.64 (s, 1H), 8.13 (d, J=7.4Hz, 1H), 7.88 (d, J=7.0Hz, 1H), 7.41-7.33 (m, 2H), 6.39 (s, 1H), 2.86 (s, 3H), 2.41 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C
13h
13n
2(M
*) 197.1073, found:197.1086.
Embodiment 16:
The present embodiment is the synthetic of imidazoles [1,2-a] quinoxaline, and take 2-Iodoaniline, imidazoles-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol imidazoles-2-formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 100%, this imidazoles [1,2-a] quinoxaline fusing point is 124-126 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3); δ 9.13 (s, 1H), 8.15-8.13 (m, 2H), 7.93-7.91 (m, 1H), 7.83 (s, 1H), 7.70-7.66 (m, 1H), 7.63-7.59 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
10h
8n
3(M
*) 170.0712, found:170.0724.
Embodiment 17:
The present embodiment is the synthetic of benzoglyoxaline [1,2-a] quinoxaline, and take 2-Iodoaniline, benzimidazolyl-2 radicals formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol benzimidazolyl-2 radicals formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 98%, this benzoglyoxaline [1,2-a] quinoxaline fusing point is 182-184 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 9.20 (s, 1H), 8.35 (d, J=8.1Hz, 1H), 8.28 (d; J=7.4Hz, 1H), 8.12 (d, J=7.8Hz, 1H), 8.06 (d; J=7.3Hz, 1H), 7.72-7.69 (m, 1H), 7.58-7.52 (m, 3H); High resolution mass spectrum: m/z (%), calcd for C
14h
10n
3(M
*) 219.0797, found:219.0789.
Embodiment 18:
The present embodiment is the synthetic of indoles [1,2-a] quinoxaline, and take 2-Iodoaniline, indoles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol indoles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 94%, this indoles [1,2-a] quinoxaline fusing point is 109-112 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 8.94 (s, 1H), 8.44 (m, 2H), 7.98 (m, 2H), 7.62 (t, J=7.7Hz, 1H), 7.56 (t, J=7.5Hz, 1H), 7.47-7.42 (m, 2H), 7.15 (s, 1H); High resolution mass spectrum: m/z (%), calcd for C
15h
11n
2(M
*) 219.0916, found:219.0933.
Embodiment 19:
The present embodiment is the synthetic of 9-methoxy-Indole [1,2-a] quinoxaline, and take 2-Iodoaniline, 5-methoxyl group-indoles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 5-methoxyl group-indoles-2 formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 93%, this 9-methoxy-Indole [1,2-a] quinoxaline fusing point is 133-135 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 8.89 (s, 1H), 8.35 (d, J=8.3Hz, 1H); (8.27 d, J=8.3Hz, 1H), 7.97 (d; J=7.8Hz, 1H), 7.58 (t, J=7.8Hz; 1H), 7.41 (t, J=7.7Hz, 1H); (7.28 broads, 1H), 7.18-7.16 (m, 1H); (7.03 s, 1H), 3.92 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C
16h
13n
2o(M
*) 249.1022, found:249.1028.
Embodiment 20:
The present embodiment is 8,9,10,11,12, synthesizing of 13-hexahydro--1H-cyclooctane-pyrroles [1,2-a] quinoxaline, with 2-Iodoaniline, 4,5,6,7,8,9-hexahydro--1H-cyclooctane-pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) are raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 4,5 in the 25ml eggplant-shape bottle, 6; 7; 8,9-hexahydro--1H-cyclooctane-pyrrole-2-aldehyde, 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), argon shield, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 91%, this 8,9,10,11,12,13-hexahydro--1H-cyclooctane-pyrroles [1,2-a] quinoxaline is the soft type solid; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3) δ 8.64 (s, 1H), 8.17 (dd, J=8.4,1.2Hz; 1H), 7.94 (dd, J=7.8,1.8Hz, 1H); (7.47-7.36 m, 2H), 6.70 (s, 1H); (3.40-3.37 m, 2H), 2.82-2.79 (m, 2H); (1.99-1.92 m, 2H), 1.73-1.67 (m, 2H); (1.58-1.52 m, 2H), 1.38-1.32 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
17h
19n
2o(M
*) 251.1542, found:251.1566.
Embodiment 21:
The present embodiment is 11-methoxyl group-8,9-dihydrobenzo indoles [1,2-a] quinoxaline synthetic, and with 2-Iodoaniline, 7-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) are raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 7-methoxyl group-4 in the 25ml eggplant-shape bottle; 5-dihydro-benzindole-2-formaldehyde; 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 91%, these 11-methoxyl group-8,9-dihydrobenzo indoles [1,2-a] quinoxaline fusing point is 174-178 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 8.71 (s, 1H), 8.19 (d, J=8.3Hz, 1H), 7.94 (d; J=8.0Hz, 1H), 7.64 (d, J=8.6Hz, 1H); (7.42 t, J=7.2Hz, 1H), 7.34 (t, J=7.8Hz; 1H), 6.93-6.92 (m, 1H), 6.83-6.80 (m, 1H); (6.78 s, 1H), 3.87 (s, 3H), 2.97 (t; J=6.5Hz, 2H), 2.81 (t, J=7.3Hz, 2H); High resolution mass spectrum: m/z (%), calcd for C
20h
17n
2o(M
*) 301.1335, found:301.1349.
Embodiment 22:
The present embodiment is the synthetic of 1-phenyl-pyrroles [1,2-a] quinoxaline, and take 2-Iodoaniline, 5 – phenyl-pyrrole-2-aldehydes, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 5 – phenyl-pyrrole-2-aldehydes in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 94%, this 1-phenyl-pyrroles [1,2-a] quinoxaline is the soft type solid; Nucleus magnetic hydrogen spectrum (500Hz, CDCl
3): δ 8.70 (s, 1H), 7.82 (d, J=8.0Hz; 1H), 7.40-7.35 (m, 5H), 7.29 (d; J=8.5Hz, 1H), 7.22 (t, J=7.7Hz; 1H), 7.00 (t, J=8.1Hz, 1H); (6.84 d, J=4.0Hz, 1H); (6.64 d, J=4.0Hz, 1H); High resolution mass spectrum: m/z (%), calcd for C
17h
13n
2(M
*) 245.1073, found:245.1094.
Embodiment 23:
The present embodiment is the synthetic of the fluoro-7-skatole of 9-[1,2-a] quinoxaline, and take 2-Iodoaniline, the fluoro-3-skatole of 5--2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the fluoro-3-skatole of 0.215mmol 5--2-formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 91%, the fluoro-7-skatole of this 9-[1,2-a] quinoxaline is 170-171 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3): δ 8.88 (s, 1H), 8.25-8.21 (m, 2H); (7.93 dd, J=7.9,1.4Hz, 1H); (7.56-7.52 m, 1H), 7.45 (dd; J=8.9,2.6Hz, 1H); (7.40-7.36 m, 1H), 7.27-7.22 (m; 1H), 2.57 (s, 3H); High resolution mass spectrum: m/z (%), calcd forC
16h
12fN
2o(M
*) 251.0979, found:251.0958.
Embodiment 24:
The present embodiment is the synthetic of 2-methyl-pyrazoles [1,5-a] quinoxaline, and take 2-Iodoaniline, 3-methyl-pyrazoles-5-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 3-methyl-pyrazoles-5-formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 93%, this 2-methyl-pyrazoles [1,5-a] quinoxaline fusing point is 89-91 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3): δ 8.95 (s, 1H), 8.43 (dd, J=8.3,1.0Hz, 1H), 8.04 (dd, J=8.1,1.0Hz, 1H), 7.68-7.63 (m, 1H), 7.55-7.51 (m, 1H), 6.64 (s, 1H), 2.59 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C
11h
10n
3o(M
*) 184.0869, found:184.0886.
Embodiment 25:
The present embodiment is the synthetic of 2-methyl-pyrazoles [1,5-a] quinoxaline, and take 2-chloroaniline, 3-methyl-pyrazoles-5-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 3-methyl-pyrazoles-5-formaldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-chloroaniline, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 41%, this 2-methyl-pyrazoles [1,5-a] quinoxaline fusing point is 89-91 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3): δ 8.95 (s, 1H), 8.43 (dd, J=8.3,1.0Hz, 1H), 8.04 (dd, J=8.1,1.0Hz, 1H), 7.68-7.63 (m, 1H), 7.55-7.51 (m, 1H), 6.64 (s, 1H), 2.59 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C
11h
10n
3o(M
*) 184.0869, found:184.0886.
Embodiment 26:
The present embodiment is the synthetic of pyrido pyrroles [1,2-a] pyrazine, and take 2-amino-3-iodine pyridine, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, 0.215mmol 2-amino-3-iodine pyridine, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), argon shield, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 94%, this pyrido pyrroles [1,2-a] pyrazine fusing point is 170-172 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 9.01 (s, 1H), 8.76-8.74 (m, 1H), 8.22-8.19 (m, 1H), 7.97-7.96 (m, 1H), 7.45 (dd, J=8.2,4.6Hz, 1H), 6.96-6.92 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
10h
8n
3(M
*) 170.0712, found:170.0729.
Embodiment 27:
The present embodiment is the synthetic of pyrido pyrroles [1,2-h] pteridine, and take 5-amino-4-iodine pyrimidine, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, 0.215mmol 5-amino-4-iodine pyrimidine, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 90%, this pyrido pyrroles [1,2-h] pteridine fusing point is 122-123 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 9.24 (s, 1H), 9.06 (s, 1H), 8.82 (s, 1H), 8.34-8.33 (m, 1H), 7.05-7.04 (m, 1H), 6.99-6.97 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
9h
7n
4(M
*) 171.0665, found:171.0676.
Embodiment 28:
The present embodiment is the synthetic of 8-trifluoromethyl pyrpole [1,2-a] quinoxaline, and take 4-amino-3-iodine phenylfluoroform, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-iodine phenylfluoroform, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.Productive rate 93%, this 8-trifluoromethyl pyrpole [1,2-a] quinoxaline fusing point is 133-134 ℃; Nucleus magnetic hydrogen spectrum (300Hz, CDCl
3): δ 8.85 (s, 1H), 8.09 (s, 1H), 8.05-8.03 (m, 1H), 7.98-7.96 (m, 1H), 7.67-7.65 (m, 1H), 6.97-6.96 (m, 1H), 6.94-6.92 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
12h
8f
3n
2(M
*) 237.0634, found:237.0650.
Embodiment 29:
The present embodiment is the synthetic of 8-formonitrile HCN pyrroles [1,2-a] quinoxaline, and take 4-amino-3-ioxynil, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-ioxynil, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 90%, this 8-formonitrile HCN pyrroles [1,2-a] quinoxaline fusing point is 273-275 ℃; Nucleus magnetic hydrogen spectrum (400Hz, d-6DMSO): δ 9.15 (s, 1H), 9.01 (d; J=1.5Hz, 1H), 8.76-8.74 (m; 1H), 8.05 (d, J=8.4Hz; 1H), 7.94 (dd, J=8.4; 1.6Hz, 1H), 7.31-7.29 (m; 1H), 7.13 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
12h
8n
3(M
*) 194.0712, found:194.0728.
Embodiment 30:
The present embodiment is the synthetic of 8-methyl-formiate pyrroles [1,2-a] quinoxaline, and take 4-amino-3-iodo-benzoic acid methyl esters, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) is raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-iodo-benzoic acid methyl esters, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 90%, this 8-methyl-formiate pyrroles [1,2-a] quinoxaline fusing point is 235-240 ℃; Nucleus magnetic hydrogen spectrum (400Hz, d-6DMSO): δ 8.95 (s, 1H), 8.78-8.77 (m, 1H), 8.64-8.63 (m; 1H), 8.00 (dd, J=8.4,1.5Hz, 1H), 7.93 (d; J=8.4Hz, 1H), 7.06 (m, 1H), 6.97-6.95 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C
12h
9n
2o
2(M
*) 213.0658, found:213.0670.
Embodiment 31:
The present embodiment is the synthetic of 7-fluorine pyrroles [1,2-a] quinoxaline, and the fluoro-2-Iodoaniline of the 5-of take, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) are raw material, and its reaction formula is as follows:
Preparation method: add the 0.215mmol pyrrole-2-aldehyde in the 25ml eggplant-shape bottle, the fluoro-2-Iodoaniline of 0.215mmol 5-, 0.54mmol potassium tert.-butoxide; add again the 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection, 100 ℃ are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered and obtains white solid after cooling, extraction, drying, underpressure distillation, washing, recrystallization.
Productive rate 96%, this 7-fluorine pyrroles [1,2-a] quinoxaline fusing point is 166-167 ℃; Nucleus magnetic hydrogen spectrum (400Hz, CDCl
3): δ 8.78 (s, 1H), 7.86 (broad s, 1H), 7.78 (dd, J=9.0,5.0Hz, 1H), 7.61 (dd, J=9.4,2.7Hz, 1H), 7.26-7.21 (m, 1H), 6.90-6.85 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C
11h
8fN
2(M
*) 187.0666, found:187.0680.
Claims (7)
1. a pyrroles [1; 2-a] synthetic method of quinoxaline derivatives; it is characterized in that: get 2-halogen arylamine and 2-formyl radical azole compounds is raw material; by the amount of substance ratio, be that 1～3:1 is dissolved in organic solvent; add alkaline medium, under protection of inert gas, 80～100 ℃ are stirred reaction in 12～24 hours; obtain pyrroles [1,2-a] quinoxaline derivatives.
2. synthetic method according to claim 1 is characterized in that: described alkaline medium is a kind of in trimethyl carbinol lithium, sodium tert-butoxide, potassium tert.-butoxide, lithium hydroxide or sodium hydroxide.
3. synthetic method according to claim 1, it is characterized in that: alkaline medium and 2-formyl radical azole compounds amount of substance ratio are 1～3:1.
4. synthetic method according to claim 1 is characterized in that: described organic solvent is a kind of in dimethyl sulfoxide (DMSO), dimethyl formamide or toluene.
5. synthetic method according to claim 1, is characterized in that: described inert nitrogen gas or argon gas.
6. synthetic method according to claim 1, it is characterized in that: the structural formula of described 2-formyl radical azole compounds is as follows:
7. synthetic method according to claim 1, it is characterized in that: the structural formula of described 2-halogen arylamine is as follows:
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| CN115028635A (en) * | 2022-05-11 | 2022-09-09 | 中捷四方生物科技股份有限公司 | Skeleton transition type berberine analogue and application thereof in preventing and treating agricultural diseases |
| CN115028635B (en) * | 2022-05-11 | 2023-08-15 | 中捷四方生物科技股份有限公司 | Skeleton transition type berberine analogue and application thereof in preventing and treating agricultural diseases |
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