CN105272793A - 一种合成芳基腙的方法 - Google Patents
一种合成芳基腙的方法 Download PDFInfo
- Publication number
- CN105272793A CN105272793A CN201410332120.1A CN201410332120A CN105272793A CN 105272793 A CN105272793 A CN 105272793A CN 201410332120 A CN201410332120 A CN 201410332120A CN 105272793 A CN105272793 A CN 105272793A
- Authority
- CN
- China
- Prior art keywords
- arh
- aryl
- reaction
- phenylhydrazine
- cdcl
- 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
- -1 aryl hydrazone Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 52
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 claims abstract description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 8
- 150000003624 transition metals Chemical class 0.000 claims abstract description 8
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 5
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 105
- 239000011541 reaction mixture Substances 0.000 claims description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 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 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 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
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 abstract description 11
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- 239000003795 chemical substances by application Substances 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 30
- 239000003208 petroleum Substances 0.000 description 30
- 238000002390 rotary evaporation Methods 0.000 description 30
- 238000000967 suction filtration Methods 0.000 description 30
- BRFMIAWBJODPRI-UHFFFAOYSA-N C1(=CC=CC=C1)NN.CC1(C(=O)O)CC(C(=O)O)=CC=C1 Chemical compound C1(=CC=CC=C1)NN.CC1(C(=O)O)CC(C(=O)O)=CC=C1 BRFMIAWBJODPRI-UHFFFAOYSA-N 0.000 description 21
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 10
- 229960004217 benzyl alcohol Drugs 0.000 description 10
- 235000019445 benzyl alcohol Nutrition 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 8
- 239000002994 raw material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- MBYQPPXEXWRMQC-UHFFFAOYSA-N (2-chlorophenyl)methanol Chemical compound OCC1=CC=CC=C1Cl MBYQPPXEXWRMQC-UHFFFAOYSA-N 0.000 description 1
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 description 1
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 1
- SQMOOVFBFVTTGF-UHFFFAOYSA-N 1-benzyl-1-phenylhydrazine Chemical compound C=1C=CC=CC=1N(N)CC1=CC=CC=C1 SQMOOVFBFVTTGF-UHFFFAOYSA-N 0.000 description 1
- VKXUWCNLFZXHEF-UHFFFAOYSA-N 1-butyl-1-phenylhydrazine Chemical compound CCCCN(N)C1=CC=CC=C1 VKXUWCNLFZXHEF-UHFFFAOYSA-N 0.000 description 1
- NQSIARGGPGHMCG-UHFFFAOYSA-N 1-ethyl-1-phenylhydrazine Chemical compound CCN(N)C1=CC=CC=C1 NQSIARGGPGHMCG-UHFFFAOYSA-N 0.000 description 1
- SIRPHJCQZYVEES-UHFFFAOYSA-N 1-methylbenzimidazole-2-carbaldehyde Chemical compound C1=CC=C2N(C)C(C=O)=NC2=C1 SIRPHJCQZYVEES-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- MOOUWXDQAUXZRG-UHFFFAOYSA-N 4-(trifluoromethyl)benzyl alcohol Chemical compound OCC1=CC=C(C(F)(F)F)C=C1 MOOUWXDQAUXZRG-UHFFFAOYSA-N 0.000 description 1
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 1
- WSCRYJBDRCQXIG-LDADJPATSA-N CNN(C(C=C1)=CCC1[I]=C)/N=C/c1ccccc1 Chemical compound CNN(C(C=C1)=CCC1[I]=C)/N=C/c1ccccc1 WSCRYJBDRCQXIG-LDADJPATSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- NUIQKBRRMNLBBE-LFIBNONCSA-N N-[(E)-(2-chlorophenyl)methylideneamino]-N-methylaniline Chemical compound ClC1=C(\C=N\N(C2=CC=CC=C2)C)C=CC=C1 NUIQKBRRMNLBBE-LFIBNONCSA-N 0.000 description 1
- XSFDFAXZUXILFX-LFIBNONCSA-N N-[(E)-benzylideneamino]-4-fluoro-N-methylaniline Chemical compound C(/C1=CC=CC=C1)=N\N(C)C1=CC=C(C=C1)F XSFDFAXZUXILFX-LFIBNONCSA-N 0.000 description 1
- LDPZXZJQFOGZNH-SFQUDFHCSA-N N-[(E)-benzylideneamino]-N,3,5-trimethylaniline Chemical compound C(/C1=CC=CC=C1)=N\N(C)C1=CC(=CC(=C1)C)C LDPZXZJQFOGZNH-SFQUDFHCSA-N 0.000 description 1
- ATNMXDUZNJUXEY-OBGWFSINSA-N N-[(E)-benzylideneamino]-N-butylaniline Chemical compound C(/C1=CC=CC=C1)=N\N(C1=CC=CC=C1)CCCC ATNMXDUZNJUXEY-OBGWFSINSA-N 0.000 description 1
- CYGSNXYALVWYKA-DTQAZKPQSA-N N-[(E)-benzylideneamino]-N-ethylaniline Chemical compound C(/C1=CC=CC=C1)=N\N(C1=CC=CC=C1)CC CYGSNXYALVWYKA-DTQAZKPQSA-N 0.000 description 1
- APCWENDGTSZNMH-YBFXNURJSA-N N-[(E)-benzylideneamino]-N-methyl-4-(trifluoromethoxy)aniline Chemical compound C(/C1=CC=CC=C1)=N\N(C1=CC=C(C=C1)OC(F)(F)F)C APCWENDGTSZNMH-YBFXNURJSA-N 0.000 description 1
- YDUPIQWQAZWYBC-ZRDIBKRKSA-N N-[(E)-butylideneamino]-N-methylaniline Chemical compound C(/CCC)=N\N(C1=CC=CC=C1)C YDUPIQWQAZWYBC-ZRDIBKRKSA-N 0.000 description 1
- ACWJLFCAVPCXKE-NTCAYCPXSA-N N-[(E)-cyclohexylmethylideneamino]-N-methylaniline Chemical compound C1(CCCCC1)\C=N\N(C1=CC=CC=C1)C ACWJLFCAVPCXKE-NTCAYCPXSA-N 0.000 description 1
- QZZUVVDITXPYDA-WYMLVPIESA-N N-[(E)-hexylideneamino]-N-methylaniline Chemical compound C(/CCCCC)=N\N(C1=CC=CC=C1)C QZZUVVDITXPYDA-WYMLVPIESA-N 0.000 description 1
- WIQWDXDWQXUHMJ-FOWTUZBSSA-N N-methyl-N-[(E)-(2-methylphenyl)methylideneamino]aniline Chemical compound CN(/N=C/C1=C(C=CC=C1)C)C1=CC=CC=C1 WIQWDXDWQXUHMJ-FOWTUZBSSA-N 0.000 description 1
- VHQXASRVEFYUSD-QGOAFFKASA-N N-methyl-N-[(E)-(4-propan-2-ylphenyl)methylideneamino]aniline Chemical compound C(C)(C)C1=CC=C(\C=N\N(C2=CC=CC=C2)C)C=C1 VHQXASRVEFYUSD-QGOAFFKASA-N 0.000 description 1
- GSBONBAFUDFYNE-YBFXNURJSA-N N-methyl-N-[(E)-[4-(trifluoromethoxy)phenyl]methylideneamino]aniline Chemical compound CN(/N=C/C1=CC=C(C=C1)OC(F)(F)F)C1=CC=CC=C1 GSBONBAFUDFYNE-YBFXNURJSA-N 0.000 description 1
- MPESRNFAZRABJK-YBFXNURJSA-N N-methyl-N-[(E)-[4-(trifluoromethyl)phenyl]methylideneamino]aniline Chemical compound CN(/N=C/C1=CC=C(C=C1)C(F)(F)F)C1=CC=CC=C1 MPESRNFAZRABJK-YBFXNURJSA-N 0.000 description 1
- VRTJCXCEJIAUKF-JQIJEIRASA-N N-methyl-N-[(E)-octylideneamino]aniline Chemical compound CN(/N=C/CCCCCCC)C1=CC=CC=C1 VRTJCXCEJIAUKF-JQIJEIRASA-N 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 description 1
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 1
- ZLSOZAOCYJDPKX-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]methanol Chemical compound OCC1=CC=C(OC(F)(F)F)C=C1 ZLSOZAOCYJDPKX-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- MWMPHCOEQVTURQ-SFQUDFHCSA-N n-[(e)-(3,4-dimethoxyphenyl)methylideneamino]-n-methylaniline Chemical compound C1=C(OC)C(OC)=CC=C1\C=N\N(C)C1=CC=CC=C1 MWMPHCOEQVTURQ-SFQUDFHCSA-N 0.000 description 1
- REEWSBJDSWRAGJ-LFIBNONCSA-N n-[(e)-(4-bromophenyl)methylideneamino]-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=C(Br)C=C1 REEWSBJDSWRAGJ-LFIBNONCSA-N 0.000 description 1
- FDMDTZJXGBZUKG-LFIBNONCSA-N n-[(e)-(4-chlorophenyl)methylideneamino]-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=C(Cl)C=C1 FDMDTZJXGBZUKG-LFIBNONCSA-N 0.000 description 1
- YEFRIRNSQNMGSW-LFIBNONCSA-N n-[(e)-(4-fluorophenyl)methylideneamino]-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=C(F)C=C1 YEFRIRNSQNMGSW-LFIBNONCSA-N 0.000 description 1
- UAVOVDWXWRXKPS-FOWTUZBSSA-N n-[(e)-(4-methoxyphenyl)methylideneamino]-n-methylaniline Chemical compound C1=CC(OC)=CC=C1\C=N\N(C)C1=CC=CC=C1 UAVOVDWXWRXKPS-FOWTUZBSSA-N 0.000 description 1
- PLOIADQVYIZAMA-LFIBNONCSA-N n-[(e)-benzylideneamino]-4-chloro-n-methylaniline Chemical compound C=1C=C(Cl)C=CC=1N(C)\N=C\C1=CC=CC=C1 PLOIADQVYIZAMA-LFIBNONCSA-N 0.000 description 1
- FYLXMYKKRMLCLD-FOWTUZBSSA-N n-[(e)-benzylideneamino]-4-methoxy-n-methylaniline Chemical compound C1=CC(OC)=CC=C1N(C)\N=C\C1=CC=CC=C1 FYLXMYKKRMLCLD-FOWTUZBSSA-N 0.000 description 1
- SIBYXUIQDIWMNA-FOWTUZBSSA-N n-[(e)-benzylideneamino]-n,4-dimethylaniline Chemical compound C=1C=C(C)C=CC=1N(C)\N=C\C1=CC=CC=C1 SIBYXUIQDIWMNA-FOWTUZBSSA-N 0.000 description 1
- WUSDCMLIVSVEIR-NTCAYCPXSA-N n-[(e)-benzylideneamino]-n-methylaniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=CC=C1 WUSDCMLIVSVEIR-NTCAYCPXSA-N 0.000 description 1
- MNSMWDJATBUBDS-LTGZKZEYSA-N n-benzyl-n-[(e)-benzylideneamino]aniline Chemical compound C=1C=CC=CC=1CN(C=1C=CC=CC=1)\N=C\C1=CC=CC=C1 MNSMWDJATBUBDS-LTGZKZEYSA-N 0.000 description 1
- IMZXBDGLYPAUGU-FOWTUZBSSA-N n-methyl-n-[(e)-(4-methylphenyl)methylideneamino]aniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=C(C)C=C1 IMZXBDGLYPAUGU-FOWTUZBSSA-N 0.000 description 1
- QKBLRDLXECTTBG-JLHYYAGUSA-N n-methyl-n-[(e)-3-methylbutylideneamino]aniline Chemical compound CC(C)C\C=N\N(C)C1=CC=CC=C1 QKBLRDLXECTTBG-JLHYYAGUSA-N 0.000 description 1
- XONSRLHXNRNRLZ-XMHGGMMESA-N n-methyl-n-[(e)-naphthalen-1-ylmethylideneamino]aniline Chemical compound C=1C=CC2=CC=CC=C2C=1/C=N/N(C)C1=CC=CC=C1 XONSRLHXNRNRLZ-XMHGGMMESA-N 0.000 description 1
- QHDOOEZKARKZEW-XMHGGMMESA-N n-methyl-n-[(e)-naphthalen-2-ylmethylideneamino]aniline Chemical compound C=1C=C2C=CC=CC2=CC=1/C=N/N(C)C1=CC=CC=C1 QHDOOEZKARKZEW-XMHGGMMESA-N 0.000 description 1
- BCQMHPRJRFQRPW-RVDMUPIBSA-N n-methyl-n-[(e)-pyridin-2-ylmethylideneamino]aniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=CC=N1 BCQMHPRJRFQRPW-RVDMUPIBSA-N 0.000 description 1
- HBACPPXMWLYLCP-JLHYYAGUSA-N n-methyl-n-[(e)-thiophen-2-ylmethylideneamino]aniline Chemical compound C=1C=CC=CC=1N(C)\N=C\C1=CC=CS1 HBACPPXMWLYLCP-JLHYYAGUSA-N 0.000 description 1
- OIGWAXDAPKFNCQ-UHFFFAOYSA-N p-Isopropylbenzyl alcohol Natural products CC(C)C1=CC=C(CO)C=C1 OIGWAXDAPKFNCQ-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000002097 pentamethylcyclopentadienyl group Chemical group 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 229950007908 piconol Drugs 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种合成芳基腙的方法。在反应容器中，加入芳基肼、醇、过渡金属催化剂铱络合物、碱和对二甲苯，反应混合物在110-150oC条件下反应，反应结束后冷却到室温，柱分离得到目标化合物。同现有技术相比，本发明从芳基肼和醇作为起始原料发生偶联反应，直接合成芳基腙。和传统的芳基肼和醛反应相比，醇具有低毒，廉价，容易获得和便于储存等优点，因此，该反应符合绿色化学的要求，具有很好的应用前景。
Description
技术领域
本发明属有机合成化学技术领域，具体涉及一种合成芳基腙的方法。
背景技术
芳基腙是一类重要的含氮杂环化合物，是吲哚、卡唑、吡唑和吲唑等杂环化合物的重要合成中间体((a)Muller,S.；List,B.Angew.Chem.Int.Ed.2009,48,9975-9978.(b)Thiel,O.R.；Achmatowicz,M.M.；Reichelt,A.；Larsen,R.D.Angew.Chem.Int.Ed.2010,49,8395-8398.(c)Hernández,S.；Moreno,I.；SanMartin,R.；Gómez,G.；Herrero,M.T.；Domínguez,E.J.Org.Chem.2010,75,434-441.(d)Guru,M.M.；Ali,M.A.；Punniyamurthy,T.J.Org.Chem.2011,76,5295-5308.(e)Aljaar,N.；Conrad,J.；Beifuss,U.J.Org.Chem.2013,78,1045-1053.(f)Duan,X.Y.；Yang,X.L.；Fang,R.；Peng,X.X.；Yu,W.；Han,B.J.Org.Chem.2013,78,10692-10704.(g)Martinez,A.；Webber,M.J.；Muller,S.；List,B.Angew.Chem.Int.Ed.2013,52,9486-9490)。这类化合物本身也展现了明确的生物活性。例如，作为巨噬细胞游走(MIF)抑制剂，疟原虫拮抗剂，单胺氧化酶(MAO)抑制剂，蛋白络氨酸磷酸酶(Shp2)抑制剂等((a)Dabideen,D.R.；Cheng,K.F.；Aljabari,B.；Miller,E.J.；Pavlov,V.A.；Al-Abed,Y.J.Med.Chem.2007,50,1993-1997.(b)Baliani,A.；Bueno,G.J.；Stewart,M.L.；Yardley,V.；Brun,R.；Barrett,M.P.；Gilbert,I.H.J.Med.Chem.2005,48,5570-5579.(c)Chimenti,F.；Maccioni,E.；Secci,D.；Bolasco,A.；Chimenti,P.；Granese,A.；Befani,O.；Turini,P.；Alcaro,S.；Ortuso,F.；Cardia,M.C.；Distinto,S.J.Med.Chem.2007,50,707-712.(d)Lawrence,H.R.；Pireddu,R.；Chen,L.；Luo,Y.；Sung,S.S.；Szymanski,A.M..；Yip,M.L.R.；Guida,W.C.；Sebti,S.M.；Wu,J.；Lawrence,N.J.J.Med.Chem.2008,51,4948-4956.(e)Fattorusso,C.；Campiani,G.；Kukreja,G.；Persico,M.；Butini,S.；Romano,M.P.；Altarelli,M.；Ros,S.；Brindisi,M.；Savini,L.；Novellino,E.；Nacci,V.；Fattorusso,E.；Parapini,S.；Basilico,N.；Taramelli,D.；Yardley,V.；Croft,S.；Borriello,M.；Gemma,S.J.Med.Chem.2008,51,1333-1343)。合成芳基腙的传统方法是通过芳肼和羰基化合物发生缩合反应。然而，羰基化合物，特别是醛是高毒性的物质，不稳定，也很难长时间储存(Downing,R.S.；Kunkeler,P.J.TheFischerIndoleSynthesis.InFineChemicalsthroughHeterogeneousCatalysis,1sted.；R.A.Sheldon,H.vanBekkum,Eds,Wiley-VCHVerlagGmbH:Weinheim,Germany,2001；pp178-179)。另一种是在钯等催化剂催化条件下，通过腙和卤代烃发生偶联反应获得，此法虽然使用范围也挺广，但是此法原子经济性较低，而且反应生成的副产物氢卤酸对环境造成污染((a)Wagaw,S.；Yang,B.H.；Buchwald,S.L.J.Am.Chem.Soc.1998,120,6621-6622.(b)Wagaw,S.；Yang,B.H.；Buchwald,S.L.J.Am.Chem.Soc.1999,121,10215-10263.(c)Thiel,O.R.；Achmatowicz,M.M.；Reichelt,A.；Larsen,R.D.Angew.Chem.Int.Ed.2010,49,8395-8398).
发明内容
本发明提供一种合成芳基腙(式Ⅰ)的新方法
其包含反应物芳基肼(式Ⅱ)
和醇(式III)反应
反应是在催化剂和碱存在下发生，其反应通式为
其中，R1代表一或二个取代基，选自甲基、甲氧基、卤素、三氟甲氧基；
R2代表甲基、乙基、丁基、苄基；
R3代表一个取代基，选自苯基、烷基、单或多取代芳基；其中，单或多取代芳基优选甲基苯基、异丙基苯基、甲氧基苯基、二甲氧基苯基、三氟甲基苯基、三氟甲氧基苯基、卤代苯基、吡啶基、噻酚基或萘基；烷基优选C3-C7烷基。
本发明通过下述技术方法实现：
在反应容器中，加入芳基肼、醇、过渡金属催化剂铱络合物、碱和对二甲苯，反应混合物在110-150℃条件下反应数小时后，冷却到室温。
其中，过渡金属催化剂为金属铱络合物，选自[Cp*IrCl2]2(Cp*＝pentamethylcyclopentadienyl)、[IrCl(cod)]2(cod＝1,5-cyclooctadienyl)；碱选自氢氧化钠、氢氧化钾、叔丁醇钾；过渡金属催化剂用量相对于芳基肼摩尔比为0.2-0.5mol％；醇相对于芳基肼摩尔比为1.2-3；碱相对于芳基肼摩尔比为0.2-1.0；反应温度为110-150℃；反应时间为8-18小时。
同现有技术相比，本发明从芳基肼和醇作为起始原料发生偶联反应，直接合成芳基腙。和传统的芳基肼和醛反应相比，醇具有低毒，廉价，容易获得和便于储存等优点，因此，该反应符合绿色化学的要求，具有很好的应用前景。
具体实施方式
展示一下实例来说明本发明的某些实施例，且不应解释为限制本发明的范围。对本发明公开的内容可以同时从材料，方法和反应条件上进行许多改进，变化和改变。所有这些改进，变化和改变均确定地落入本发明的精神和范围之内。
实施例1:2-亚苄基-1-甲基-1-苯肼
(E)-2-benzylidene-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(130mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：85％
1HNMR(500MHz,CDCl3)δ7.70(d,J＝7.7Hz,2H,ArH),7.50(s,1H,ArCH＝N),7.40-7.25(m,7H,ArH),6.93(t,J＝7.2Hz,1H,ArH),3.43(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.9,136.8,131.8,129.0,128.5,127.7,126.0,120.5,115.2,33.0.
实施例2:1-甲基-2-(4-甲基亚苄基)-1-苯肼
(E)-1-methyl-2-(4-methylbenzylidene)-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、4-甲基苯甲醇(147mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：89％
1HNMR(500MHz,CDCl3)δ7.59(d,J＝8.1Hz,2H,ArH),7.49(s,1H,ArCH＝N),7.38(d,J＝8.2Hz,2H,ArH),7.32(t,J＝8.0Hz,2H,ArH),7.17(d,J＝8.0Hz,2H,ArH),6.92(t,J＝7.2Hz,1H,ArH),3.41(s,3H,CH3),2.36(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.0,137.6,134.0,132.1,129.3,129.0,126.0,120.3,115.1,32.9,21.3；HRMS-EI(70eV)m/zcalcdforC15H17N2[M+H]+225.1392,found225.1383.
实施例3:1-甲基-2-(2-甲基亚苄基)-1-苯肼
(E)-1-methyl-2-(2-methylbenzylidene)-1-phenylhydrazine
将1-甲基-1-苯肼(122.08mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、2-甲基苯甲醇(147mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在150℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％
1HNMR(500MHz,CDCl3)δ7.91(d,J＝7.6Hz,1H,ArH),7.67(s,1H,ArCH＝N),7.39-7.37(m,2H,ArH),7.34-7.30(m,2H,ArH),7.24-7.21(m,1H,ArH),7.17-7.16(m,2H,ArH),3.42(d,J＝0.8Hz,3H,CH3),2.50(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.0,135.1,134.6,130.7,130.5,129.0,127.5,126.1,125.8,120.5,115.2,33.0,20.0；HRMS(ESI)m/zcalcdforC15H17N2[M+H]+225.1392,found225.1388.
实施例4:2-(4-异丙基亚苄基)-1-甲基-1-苯肼
(E)-2-(4-isopropylbenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、4-异丙基苯甲醇(180mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：86％
1HNMR(500MHz,CDCl3)δ7.62(d,J＝8.2Hz,2H,ArH),7.48(s,1H,ArCH＝N),7.38-7.36(m,2H,ArH),7.33-7.29(m,2H,ArH),7.23-7.22(m,2H,ArH),6.91(t,J＝7.1Hz,1H,ArH),3.39(d,J＝0.7Hz,3H,CH3),2.91(heptet,J＝7.0Hz,1H,CH),1.26(d,J＝7.0Hz,6H,CH3)；13CNMR(125MHz,CDCl3)δ148.6,147.9,134.4,132.0,128.9,126.6,126.1,120.3,115.1,33.9,32.9,23.9.HRMS(ESI)m/zcalcdforC17H21N2[M+H]+253.1705,found253.1700.
实施例5:2-(4-甲氧基亚苄基)-1-甲基-1-苯肼
(E)-2-(4-methoxybenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、4-甲氧基苯甲醇(166mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：87％
1HNMR(500MHz,CDCl3)δ7.64(d,J＝8.3Hz,2H,ArH),7.48(s,1H,ArCH＝N),7.37(d,J＝8.4Hz,2H,ArH),7.31(t,J＝7.6Hz,2H,ArH),6.92-6.89(m,3H,ArH),3.83(s,3H,OCH3),3.40(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ159.5,148.0,131.9,129.7,129.0,127.3,120.2,115.0,114.0,55.3,33.0.HRMS(ESI)m/zcalcdforC15H17N2O[M+H]+241.1341,found241.1332.
实施例6:2-(3,4-二甲氧基亚苄基)-1-甲基-1-苯肼
(E)-2-(3,4-dimethoxybenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、3,4-二甲氧基苯甲醇(202mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：85％
1HNMR(500MHz,CDCl3)δ7.47(s,1H,ArCH＝N,7.40(s,1H,ArH),7.37-7.30(m,4H,ArH),7.12(d,J＝8.4Hz,1H,ArH),6.92(t,J＝7.0Hz,1H,ArH),6.87(d,J＝8.3Hz,1H,ArH),3.96(s,3H,OCH3),3.91(s,3H,OCH3),3.42(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ149.3,149.1,148.0,132.0,130.0,128.9,120.2,119.8,115.1,110.9,107.7,55.9,55.8,33.1.
实施例7:2-(4-氟亚苄基)-1-甲基-1-苯肼
(E)-2-(4-fluorobenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(28.0mg,0.5mmol)、4-氟苯甲醇(151mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：75％
1HNMR(500MHz,CDCl3)δ7.67(t,J＝6.8Hz,2H,ArH),7.47(s,1H,ArCH＝N),7.38-7.31(m,4H,ArH),7.06(t,J＝8.4Hz,2H,ArH),6.94(t,J＝7.0Hz,1H,ArH),3.42(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ162.5(d,JC-F＝245.7Hz),147.8,133.0,130.7,129.0,127.5(d,JC-F＝7.6Hz),120.6,115.5(d,JC-F＝21.6Hz),115.3,33.1；HRMS-EI(70eV)m/zcalcdforC14H14FN2[M+H]+229.1141,found229.1134.
实施例8:2-(4-氯亚苄基)-1-甲基-1-苯肼
(E)-2-(4-chlorobenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122.08mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.5mmol)、4-氯苯甲醇(171.10mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：87％
1HNMR(500MHz,CDCl3)δ7.62(d,J＝8.4Hz,2H,ArH),7.43(s,1H,ArCH＝N),7.37-7.31(m,6H,ArH),6.95(t,J＝7.1Hz,1H,ArH),3.41(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.7,135.3,133.1,130.3,129.0,128.7,127.1,120.8,115.3,33.1.
实施例9:2-(2-氯亚苄基)-1-甲基-1-苯肼
(E)-2-(2-chlorobenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.5mmol)、2-氯苯甲醇(171mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在150℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：83％
1HNMR(500MHz,CDCl3)δ8.07(d,J＝8.1Hz,1H,ArH),7.77(s,1H,ArCH＝N),7.37-7.35(m,2H,ArH),7.32-7.28(m,3H,ArH),7.23(t,J＝7.5Hz,1H,ArH),7.15-7.11(m,1H,ArH),6.94(t,J＝6.9Hz,1H,ArH),3.38(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.6,133.9,132.6,129.6,129.0,128.3,128.1,126.8,126.2,120.9,115.4,33.2；HRMS-EI(70eV)m/zcalcdforC14H14ClN2[M+H]+245.0846,found245.0841.
实施例10:2-(4-溴亚苄基)-1-甲基-1-苯肼
(E)-2-(4-bromobenzylidene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.5mmol)、4-溴苯甲醇(224mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：87％
1HNMR(500MHz,CDCl3)δ7.56(d,J＝8.6Hz,2H,ArH),7.48(d,J＝8.5Hz,2H,ArH),7.42(s,1H,ArCH＝N),7.38-7.31(m,4H,ArH),6.95(t,J＝7.1Hz,1H,ArH),3.42(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.7,135.8,131.6,130.4,129.0,127.4,121.3,120.9,115.4,33.2；HRMS-EI(70eV)m/zcalcdforC14H14BrN2Na[M+Na]+311.0160,found311.0157.
实施例11:1-甲基-1-苯基-2-(4-三氟甲基亚苄基)肼
(E)-1-methyl-1-phenyl-2-(4-(trifluoromethyl)benzylidene)hydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(56.0mg,1.0mmol)、4-三氟甲基苯甲醇(211mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：81％
1HNMR(500MHz,CDCl3)δ7.77(d,J＝7.0Hz,2H,ArH),7.60(d,J＝7.4Hz,2H,ArH),7.48(s,1H,ArCH＝N),7.40-7.33(m,4H,ArH),6.98(t,J＝6.6Hz,1H,ArH),3.45(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.6,140.3,129.8,129.1,129.0(q,JC-F＝32.1Hz),126.0,125.5(q,JC-F＝3.1Hz),124.3(q,JC-F＝270.4Hz),121.3,115.6,33.3；HRMS-EI(70eV)m/zcalcdforC15H13F3N2Na[M+Na]+301.0929,found301.0927.
实施例12:1-甲基-1-苯基-2-(4-三氟甲氧基亚苄基)肼
(E)-1-methyl-1-phenyl-2-(4-(trifluoromethoxy)benzylidene)hydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(56.0mg,1.0mmol)、4-三氟甲氧基苯甲醇(231mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：88％
1HNMR(500MHz,CDCl3)δ7.70(d,J＝8.8Hz,2H,ArH),7.46(s,1H,ArCH＝N),7.38-7.31(m,4H,ArH),7.21(d,J＝8.4Hz,2H,ArH),6.95(tt,J＝7.1HzandJ＝1.3Hz,1H,ArH),3.43(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.5,147.7,135.6,130.0,129.0,127.1,121.1,120.9,120.5(q,JC-F＝255.4Hz),115.4,33.1；HRMS-EI(70eV)m/zcalcdforC15H14F3N2O[M+H]+295.1058,found295.1053.
实施例13:1-甲基-2-(1-亚萘苄基)-1-苯基肼
(E)-1-methyl-2-(naphthalen-1-ylmethylene)-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,1.0mmol)、1-萘甲醇(189mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在150℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：78％
1HNMR(500MHz,CDCl3)δ8.66(d,J＝8.5Hz,1H,ArH),8.17(s,1H,ArCH＝N),7.99(d,J＝7.3Hz,1H,ArH),7.88(d,J＝8.2Hz,1H,ArH),7.79(d,J＝8.2Hz,1H,ArH),7.58-7.55(m,1H,ArH),7.52-7.49(m,2H,ArH),7.44(d,J＝8.1Hz,2H,ArH),7.35(t,J＝8.0Hz,2H,ArH),6.96(t,J＝7.3Hz,1H,ArH),3.55(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.0,134.0,132.1,130.6,129.1,128.7,128.1,126.2,125.6,125.6,125.0,123.9,120.7,115.4,33.1；HRMS(ESI)m/zcalcdforC18H17N2[M+H]+261.1392,found261.1384.
实施例14:1-甲基-2-(2-亚萘苄基)-1-苯基肼
(E)-1-methyl-2-(naphthalen-2-ylmethylene)-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,1.0mmol)、2-萘甲醇(190mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：81％
1HNMR(500MHz,CDCl3)δ8.07(dd,J＝8.7HzandJ＝1.6Hz,1H,ArH),7.89(s,1H,ArH),7.84-7.81(m,3H,ArH),7.66(s,1H,ArCH＝N),7.48-7.42(m,4H,ArH),7.37-7.33(m,2H,ArH),6.95(t,J＝7.3Hz,1H,ArH),3.47(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.8,134.5,133.6,133.2,131.9,129.0,128.2,127.9,127.8,126.2,126.1,125.8,123.1,120.6,115.3,33.0；HRMS-EI(70eV)m/zcalcdforC18H16N2[M+H]+261.1392,found261.1379.
实施例15:1-甲基-1-苯基-2-(2-噻吩亚苄基)肼
(E)-1-methyl-1-phenyl-2-(thiophen-2-ylmethylene)hydrazine
将1-甲基-1-苯肼(122.08mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,1.0mmol)、2-噻吩甲醇(137.00mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：87％
1HNMR(500MHz,CDCl3)δ7.68(s,1H,ArCH＝N),7.35-7.30(m,4H,ArH),7.20(d,J＝5.1Hz,1H,ArH),7.09(d,J＝3.2Hz,1H,ArH),7.01-6.99(m,1H,ArH),6.92(tt,J＝6.7HzandJ＝1.7Hz,1H,ArH),3.39(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.5,142.7,129.0,127.1,126.9,125.4,124.8,120.6,115.2,33.2.
实施例16:1-甲基-1-苯基-2-(2-吡啶亚苄基)肼
(E)-2-((2-methyl-2-phenylhydrazono)methyl)pyridine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(28.0mg,0.5mmol)、2-吡啶甲醇(131mg,1.2mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％
1HNMR(500MHz,CDCl3)δ8.54-8.52(m,1H,ArH),8.01(dt,J＝8.1HzandJ＝1.0Hz,1H,ArH),7.67(td,J＝7.8HzandJ＝1.7Hz,1H,ArH),7.62(s,1H,ArCH＝N),7.41-7.38(m,2H,ArH),7.36-7.32(m,2H,ArH),7.15-7.12(m,1H,ArH),6.98(tt,J＝7.2HzandJ＝1.2Hz,1H,ArH),3.46(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ155.8,148.9,147.4,136.1,132.5,129.0,121.8,121.2,119.0,115.6,33.3.
实施例17:2-亚丁基-1-甲基-1-苯肼
(E)-2-butylidene-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)和正丁醇(222mg,3.0mmol)依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：78％
1HNMR(500MHz,CDCl3)δ7.28-7.21(m,4H,ArHandArCH＝N),6.87-6.81(m,2H,ArH),3.20(s,3H,CH3),2.37-2.33(m,2H,CH2),1.63-1.56(m,2H,CH2),1.01-0.97(m,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.4,136.0,128.9,119.7,114.8,35.0,33.0,20.9,13.8；HRMS-EI(70eV)m/zcalcdforC11H17N2[M+H]+177.1392,found177.1385.
实施例18:2-亚己基-1-甲基-1-苯肼
(E)-2-hexylidene-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)和正己醇(307mg,3.0mmol)依次加到25mL克氏反应瓶中。反应混合物在130℃下反应18小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％
1HNMR(500MHz,CDCl3)δ7.28-7.22(m,4H,ArHandArCH＝N),6.86-6.81(m,2H,ArH),3.20(s,3H,CH3),2.38-2.34(m,2H,CH2),1.60-1.54(m,2H,CH2),1.38-1.34(m,4H,2xCH2),0.91(t,J＝6.8Hz,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.4,136.2,128.9,119.6,114.8,33.0,31.5,27.3,22.5,14.0；HRMS-EI(70eV)m/zcalcdforC13H21N2[M+H]+205.1705,found205.1700.
实施例19:2-亚辛基-1-甲基-1-苯肼
(E)-1-methyl-2-octylidene-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)和正辛醇(391mg,3.0mmol)依次加到25mL克氏反应瓶中。反应混合物在130℃下反应18小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％
1HNMR(500MHz,CDCl3)δ7.20-7.14(m,4H,ArHandArCH＝N),6.78-6.73(m,2H,ArH),3.12(s,3H,CH3),2.30-2.26(m,2H,CH2),1.48(quint,J＝7.4Hz,2H,CH2),1.32-1.18(m,8H,4xCH2),0.81(t,J＝7.0Hz,3H,CH3)；13CNMR(125MHz,CDCl3)δ148.4,136.2,128.9,119.6,114.7,33.0,32.9,31.8,29.2,29.1,27.6,22.6.14.1；HRMS-EI(70eV)m/zcalcdforC15H25N2[M+H]+233.2018,found233.2013.
实施例20:1-甲基-2-(3-甲基亚丁基)-1-苯基肼
(E)-1-methyl-2-(3-methylbutylidene)-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)和异戊醇(264mg,3.0mmol)依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：75％
1HNMR(500MHz,CDCl3)δ7.28-7.21(m,4H,ArHandArCH＝N),6.86-6.80(m,2H,ArH),3.21(s,3H,CH3),2.27-2.24(m,2H,CH2),1.88(heptet,J＝6.8Hz,1H,CH),0.98(d,J＝6.7Hz,6H,2xCH3)；13CNMR(125MHz,CDCl3)δ148.4,135.4,128.9,119.7,114.8,41.9,33.1,27.4,22.4；HRMS-EI(70eV)m/zcalcdforC12H19N2[M+H]+191.1548,found191.1545.
实施例21:2-(亚环己基)-1-甲基-1-苯肼
(E)-2-(cyclohexylmethylene)-1-methyl-1-phenylhydrazine
将1-甲基-1-苯肼(122mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)和环己基甲醇(343mg,3.0mmol)依次加到25mL克氏反应瓶中。反应混合物在130℃下反应18小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：77％
1HNMR(500MHz,CDCl3)δ7.27-7.22(m,4H,ArHandArCH＝N),6.83(t,J＝7.0Hz,1H,ArH),6.71(d,J＝5.0Hz,1H,ArH),3.18(s,3H,CH3),2.36-2.29(m,1H,CH),1.90-1.88(m,2H,CH2),1.81-1.77(m,2H,CH2),1.70-1.66(m,1H,CH),1.38-1.20(m,5H,CH2)；13CNMR(125MHz,CDCl3)δ148.5,140.3,128.9,119.5,114.6,41.2,32.7,31.3,26.2,25.8；HRMS-EI(70eV)m/zcalcdforC14H21N2[M+H]+217.1705,found217.1699.
实施例22:2-亚苄基-1-甲基-1-(4-甲基苯基)肼
(E)-2-benzylidene-1-methyl-1-(p-tolyl)hydrazine
将1-甲基-1-(4-甲基苯基)肼(136mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％
1HNMR(500MHz,CDCl3)δ7.68(d,J＝7.5Hz,2H,ArH),7.45(s,1H,ArCH＝N),7.36(t,J＝7.6Hz,2H,ArH),7.26(t,J＝8.0Hz,3H,ArH),7.12(d,J＝8.4Hz,2H,ArH),3.40(s,3H,CH3),2.31(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ145.8,136.9,131.3,130.0,129.5,128.5,127.5,126.0,115.5,33.4,20.5；HRMS-EI(70eV)m/zcalcdforC15H17N2[M+H]+225.1392,found225.1389.
实施例23:2-亚苄基-1-(3,5-二甲基苯基)-1-甲基肼
(E)-2-benzylidene-1-(3,5-dimethylphenyl)-1-methylhydrazine
将1-甲基-1-(3,5-二甲基苯基)肼(150mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％
1HNMR(500MHz,CDCl3)δ7.69(d,J＝7.8Hz,2H,ArH),7.47(s,1H,ArCH＝N),7.37(t,J＝7.4Hz,2H,ArH),7.27-7.24(m,1H,ArH),7.01(s,2H,ArH),6.60(s,1H,ArH),3.40(s,3H,CH3),2.34(s,6H,2xCH3)；13CNMR(125MHz,CDCl3)δ148.0,138.6,136.9,131.5,128.5,127.5,126.0,122.6,113.4,33.3,21.7；HRMS-EI(70eV)m/zcalcdforC16H18N2Na[M+Na]+263.1368,found263.1364.
实施例24:2-亚苄基-1-(4-甲氧基苯基)-1-甲基肼
(E)-2-benzylidene-1-(4-methoxyphenyl)-1-methylhydrazine
将1-甲基-1-(4-甲氧基苯基)肼(152mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：81％
1HNMR(500MHz,CDCl3)δ7.67(d,J＝7.8Hz,2H,ArH),7.42(s,1H,ArCH＝N),7.35(t,J＝7.6Hz,2H,ArH),7.29-7.22(m,3H,ArH),6.89(d,J＝9.1Hz,2H,ArH),3.79(s,3H,OCH3),3.38(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ154.4,142.4,137.0,131.2,128.5,127.4,125.9,117.2,114.4,55.7,34.2；HRMS-EI(70eV)m/zcalcdforC15H16N2NaO[M+Na]+263.1160,found263.1157.
实施例25:2-亚苄基-1-(4-氟苯基)-1-甲基肼
(E)-2-benzylidene-1-(4-fluorophenyl)-1-methylhydrazine
将1-甲基-1-(4-氟苯基)肼(140mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：75％
1HNMR(500MHz,CDCl3)δ7.67(d,J＝7.4Hz,2H,ArH),7.45(s,1H,ArCH＝N),7.36(t,J＝7.7Hz,2H,ArH),7.30-7.23(m,3H,ArH),7.03-6.99(m,2H,ArH),3.37(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ157.7(d,JC-F＝238.0Hz),144.5,136.6,132.0,128.6,127.7,126.0,116.6(d,JC-F＝7.3Hz),115.4(d,JC-F＝22.0Hz),33.6；HRMS-EI(70eV)m/zcalcdforC14H14FN2[M+H]+229.1141,found229.1138.
实施例26:2-亚苄基-1-(4-氯苯基)-1-甲基肼
(E)-2-benzylidene-1-(4-chlorophenyl)-1-methylhydrazine
将1-甲基-1-(4-氯苯基)肼(157mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：79％
1HNMR(500MHz,CDCl3)δ7.69(d,J＝7.2Hz,2H,ArH),7.50(s,1H,ArCH＝N),7.37(t,J＝7.7Hz,2H,ArH),7.31-7.25(m,5H,ArH),3.40(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ146.5,136.4,132.6,128.9,128.6,128.0,126.1,125.4,116.2,33.0；HRMS-EI(70eV)m/zcalcdforC14H14ClN2[M+H]+245.0846,found245.0842.
实施例27:2-亚苄基-1-甲基-1-(4-三氟甲氧基苯基)肼
(E)-2-benzylidene-1-methyl-1-(4-(trifluoromethoxy)phenyl)hydrazine
将1-甲基-1-(4-三氯甲氧基苯基)肼(206mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：83％
1HNMR(500MHz,CDCl3)δ7.68(d,J＝7.6Hz,2H,ArH),7.50(s,1H,ArCH＝N),7.39-7.33(m,4H,ArH),7.28(tt,J＝7.3HzandJ＝1.2Hz,1H,ArH),7.17(d,J＝9.0Hz,2H,ArH),3.40(s,3H,CH3)；13CNMR(125MHz,CDCl3)δ146.6,142.8,136.4,132.8,128.6,128.0,126.2,121.9,120.7(q,JC-F＝254.4Hz),115.7,32.9；HRMS-EI(70eV)m/zcalcdforC15H13F3N2ONa[M+Na]+317.0878,found317.0875.
实施例28:2-亚苄基-1-乙基-1-苯肼
(E)-2-benzylidene-1-ethyl-1-phenylhydrazine
将1-乙基-1-苯肼(136mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：80％
1HNMR(500MHz,CDCl3)δ7.71-7.69(m,2H,ArH),7.55(s,1H,ArCH＝N),7.38-7.30(m,6H,ArH),7.28-7.24(m,1H,ArH),6.92(tt,J＝7.1HzandJ＝1.2Hz,1H,ArH),4.02(q,J＝7.2Hz,2H,CH2),1.27(t,J＝7.2Hz,3H,CH3)；13CNMR(125MHz,CDCl3)δ146.8,136.9,130.9,129.1,128.5,127.6,126.0,120.3,114.7,39.6,10.1；HRMS-EI(70eV)m/zcalcdforC15H17N2[M+H]+225.1392,found225.1386.
实施例29:2-亚苄基-1-丁基-1-苯肼
(E)-2-benzylidene-1-butyl-1-phenylhydrazine
将1-丁基-1-苯肼(164mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：82％
mp64-65℃；1HNMR(500MHz,CDCl3)δ7.70(d,J＝7.8Hz,2H,ArH),7.52(s,1H,ArCH＝N),7.39-7.36(m,4H,ArH),7.32(t,J＝7.8Hz,2H,ArH),7.28-7.25(m,1H,ArH),6.92(t,J＝7.2Hz,1H,ArH),3.91(t,J＝7.9Hz,2H,CH2),1.68(quint,J＝7.8Hz,2H,CH2),1.47(sextet,J＝7.4Hz,2H,CH2),1.01(t,J＝7.4Hz,3H,CH3)；13CNMR(125MHz,CDCl3)δ147.2,136.9,130.9,129.0,128.5,127.6,126.0,120.2,114.7,45.0,26.9,20.4,13.9；HRMS-EI(70eV)m/zcalcdforC17H21N2[M+H]+253.1705,found253.1698.
实施例30:1-苄基-2-亚苄基-1-苯肼
(E)-1-benzyl-2-benzylidene-1-phenylhydrazine
将1-苄基-1-苯肼(198mg,1.0mmol)、[Cp*IrCl2]2(4.0mg,0.005mmol,0.5mol％)、氢氧化钾(16.8mg,0.3mmol)、苯甲醇(140mg,1.3mmol)和0.5mL对二甲苯依次加到25mL克氏反应瓶中。反应混合物在130℃下反应12小时后，冷却至室温，抽滤除去不溶物，旋转蒸发除去溶剂，然后通过柱层析(展开剂：乙酸乙酯/石油醚)得到纯净的目标化合物，产率：84％
mp109-110℃；1HNMR(500MHz,CDCl3)δ7.62(d,J＝8.3Hz,2H,ArH),7.42-7.39(m,3H,ArHandArCH＝N),7.36-7.31(m,6H,ArH),7.28-7.22(m,4H,ArH),6.95(t,J＝7.3Hz,1H,ArH),5.19(s,2H,CH2)；13CNMR(125MHz,CDCl3)δ147.9,136.5,135.7,132.5,129.1,129.0,128.5,127.8,127.3,126.2,126.0,120.7,114.8,50.4.
实施例31:
除用[Ir(cod)Cl]2(3.3mg,0.005mmol,0.5mol％)代替[Cp*IrCl2]2，其它反应原料，条件和产物同实施例1，产率：80％
实施例32:
除用氢氧化钠(12mg,0.3mmol,0.3equiv.)代替氢氧化钾，其它反应原料，条件和产物同实施例1，产率：73％
实施例33:
除用叔丁醇钾(33.6mg,0.3mmol,0.3equiv.)代替氢氧化钾，其它反应原料，条件和产物同实施例1，产率：78％
实施例34:
除氢氧化钾的用量为11.2mg,0.2mmol,0.2equiv.，其它反应原料，条件和产物同实施例1，产率：77％
实施例35:
除反应时间为8小时,其它反应原料，条件和产物同实施例1，产率：75％。
Claims (6)
1.一种合成芳基腙的方法，其特征在于，所述的芳基腙Ⅰ，
通过芳基肼Ⅱ
和醇III反应
反应是在过渡金属催化剂和碱存在下进行，
R1选自甲基、甲氧基、卤素、三氟甲氧基；
R2选自甲基、乙基、丁基、苄基；
R3选自苯基、烷基、单或多取代芳基，其中，单或多取代芳基为甲基苯基、异丙基苯基、甲氧基苯基、二甲氧基苯基、三氟甲基苯基、三氟甲氧基苯基、卤代苯基、吡啶基、噻酚基或萘基；烷基为C3-C7烷基；
所述方法包括如下步骤：在反应容器中，加入芳基肼、醇、过渡金属催化剂铱络合物、碱和对二甲苯，反应混合物在110-150℃条件下反应，反应结束后冷却到室温，柱分离得到目标化合物。
2.根据权利要求1所述的合成芳基腙的方法，其特征在于，过渡金属催化剂为金属铱络合物[Cp*IrCl2]2或[IrCl(cod)]2；碱选自氢氧化钠、氢氧化钾、叔丁醇钾中任意一种。
3.根据权利要求1所述的合成芳基腙的方法，其特征在于，过渡金属催化剂用量相对于芳基肼摩尔比为0.2-0.5mol％。
4.根据权利要求1所述的合成芳基腙的方法，其特征在于，醇相对于芳基肼摩尔比为1.2-3。
5.根据权利要求1所述的合成芳基腙的方法，其特征在于，碱相对于芳基肼摩尔比为0.2-1.0。
6.根据权利要求1所述的合成芳基腙的方法，其特征在于，反应时间为8-18小时。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410332120.1A CN105272793B (zh) | 2014-07-11 | 2014-07-11 | 一种合成芳基腙的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410332120.1A CN105272793B (zh) | 2014-07-11 | 2014-07-11 | 一种合成芳基腙的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105272793A true CN105272793A (zh) | 2016-01-27 |
| CN105272793B CN105272793B (zh) | 2017-02-15 |
Family
ID=55142699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410332120.1A Expired - Fee Related CN105272793B (zh) | 2014-07-11 | 2014-07-11 | 一种合成芳基腙的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105272793B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417566A (zh) * | 2017-06-15 | 2017-12-01 | 陕西师范大学 | 一种可见光催化卤代芳烃和腙类化合物合成n‑芳基腙的方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2287149A1 (en) * | 2009-08-20 | 2011-02-23 | Max-Delbrück-Centrum Für Molekulare Medizin | Enhancers of protein degradation |
-
2014
- 2014-07-11 CN CN201410332120.1A patent/CN105272793B/zh not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2287149A1 (en) * | 2009-08-20 | 2011-02-23 | Max-Delbrück-Centrum Für Molekulare Medizin | Enhancers of protein degradation |
Non-Patent Citations (3)
| Title |
|---|
| KEN-ICHI FUJITA等: "Cp*Ir-catalyzed N-alkylation of amines with alcohols. A versatile and atom economical method for the synthesis of amines", 《TETRAHEDRON》 * |
| STURINO, CLAUDIO F.: "Samarium (ii) iodide cyclizations of halo- and carbonylhydrazones", 《SAMARIUM (II) IODIDE CYCLIZATIONS OF HALO- AND CARBONYLHYDRAZONES》 * |
| YUMIKO NAKAJIMA等: "Synthesis, Structures, and Reactivity of Ruthenium Complexes with PNP-pincer Type Phosphaalkene Ligands", 《ORGANOMETALLICS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417566A (zh) * | 2017-06-15 | 2017-12-01 | 陕西师范大学 | 一种可见光催化卤代芳烃和腙类化合物合成n‑芳基腙的方法 |
| CN107417566B (zh) * | 2017-06-15 | 2020-02-21 | 陕西师范大学 | 一种可见光催化卤代芳烃和腙类化合物合成n-芳基腙的方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105272793B (zh) | 2017-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106748950B (zh) | 一种布瓦西坦及其中间体的制备方法 | |
| US20070142639A1 (en) | Process for production of amines | |
| KR20090118032A (ko) | 키랄 이리듐 아쿠아 착물 및 이를 사용한 광학 활성 히드록시 화합물의 제조 방법 | |
| CN106187852A (zh) | 一种富马酸沃诺拉赞中间体的制备方法 | |
| CN104447686B (zh) | 多取代2-吡咯吡啶衍生物及其制备方法 | |
| CN105254589A (zh) | 一种制备心力衰竭药物中间体的方法 | |
| CN105732605A (zh) | 一种艾沙康唑中间体的制备方法 | |
| CN103755628A (zh) | 2-氨基-3-碘-5-溴吡啶的合成方法 | |
| CN111072605B (zh) | 一种氟烷基取代的苯并呋喃衍生物或吲哚衍生物的制备方法 | |
| CN105272793A (zh) | 一种合成芳基腙的方法 | |
| CN102964307B (zh) | 一种达比加群酯有关物质及其制备方法 | |
| CN101508702B (zh) | 四氢喹啉和吲哚啉衍生的磷氮配体、合成方法和应用 | |
| CN107879979B (zh) | 一种右美托咪定的制备方法 | |
| CN108675950A (zh) | 一种2-烯基吲哚类化合物的合成方法 | |
| CN104478799B (zh) | 1,4-二烯丙基异喹啉的制备方法 | |
| CN102952119A (zh) | 一种雷贝拉唑钠的制备方法 | |
| CN105622613A (zh) | 一种合成伊鲁替尼的方法 | |
| JP5120962B2 (ja) | ホモアリルヒドラジドの製造方法、及びそれに用いる不斉触媒 | |
| CN114805170B (zh) | 一种新型赛洛多辛手性中间体的制备方法 | |
| CN103819396B (zh) | 一种手性的1-（3,5-二氯吡啶-4-基）-乙醇的合成方法 | |
| CN108727345B (zh) | 一种咪唑环中间体的制备方法 | |
| US11623913B2 (en) | Method of synthesizing (1R,2R)-nitroalcohol compound | |
| CN104059009A (zh) | 一种依折麦布重要中间体的合成方法 | |
| CN107400084A (zh) | 一种合成喹啉衍生物的方法 | |
| CN105801500A (zh) | 拆分艾沙康唑中间化合物消旋体的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170215 Termination date: 20170711 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |