CN101691318B - N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system - Google Patents
N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system Download PDFInfo
- Publication number
- CN101691318B CN101691318B CN 200910040649 CN200910040649A CN101691318B CN 101691318 B CN101691318 B CN 101691318B CN 200910040649 CN200910040649 CN 200910040649 CN 200910040649 A CN200910040649 A CN 200910040649A CN 101691318 B CN101691318 B CN 101691318B
- Authority
- CN
- China
- Prior art keywords
- reaction
- alkyl
- amine
- copper
- catalyzer
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- 238000006254 arylation reaction Methods 0.000 title claims abstract description 14
- 239000008346 aqueous phase Substances 0.000 title claims abstract description 7
- 239000003446 ligand Substances 0.000 title abstract description 4
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical class NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- 239000010949 copper Substances 0.000 claims abstract description 18
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001502 aryl halides Chemical class 0.000 claims abstract description 14
- 229910052802 copper Inorganic materials 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 13
- 150000001412 amines Chemical class 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 239000000758 substrate Substances 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 239000013543 active substance Substances 0.000 claims description 6
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 6
- 238000010304 firing Methods 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 4
- 150000004982 aromatic amines Chemical class 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- 150000003141 primary amines Chemical class 0.000 claims description 4
- 150000008431 aliphatic amides Chemical class 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 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
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 claims description 2
- 229960003280 cupric chloride Drugs 0.000 claims description 2
- 229960004643 cupric oxide Drugs 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- -1 adipic dihydrazide compound Chemical class 0.000 abstract description 9
- 230000007613 environmental effect Effects 0.000 abstract description 5
- 239000000047 product Substances 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 229930014626 natural product Natural products 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000575 pesticide Substances 0.000 abstract 1
- 239000002352 surface water Substances 0.000 abstract 1
- 239000004094 surface-active agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000005406 washing Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 16
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000004821 distillation Methods 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000003810 ethyl acetate extraction Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229960001866 silicon dioxide Drugs 0.000 description 10
- 238000006555 catalytic reaction Methods 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- 230000002194 synthesizing effect Effects 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- QFRIIGBAHKSVIU-UHFFFAOYSA-N n-benzyl-2-methylaniline Chemical compound CC1=CC=CC=C1NCC1=CC=CC=C1 QFRIIGBAHKSVIU-UHFFFAOYSA-N 0.000 description 3
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 3
- OBHGSIGHEBGGFS-UHFFFAOYSA-N 4-methoxy-n-phenylaniline Chemical compound C1=CC(OC)=CC=C1NC1=CC=CC=C1 OBHGSIGHEBGGFS-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 238000006887 Ullmann reaction Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- DKLYDESVXZKCFI-UHFFFAOYSA-N n,n-diphenylacetamide Chemical compound C=1C=CC=CC=1N(C(=O)C)C1=CC=CC=C1 DKLYDESVXZKCFI-UHFFFAOYSA-N 0.000 description 2
- HSZCJVZRHXPCIA-UHFFFAOYSA-N n-benzyl-n-ethylaniline Chemical compound C=1C=CC=CC=1N(CC)CC1=CC=CC=C1 HSZCJVZRHXPCIA-UHFFFAOYSA-N 0.000 description 2
- BCEHDRNCEWCNIW-UHFFFAOYSA-N n-cyclohexyl-4-methoxyaniline Chemical compound C1=CC(OC)=CC=C1NC1CCCCC1 BCEHDRNCEWCNIW-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- PIMNFNXBTGPCIL-UHFFFAOYSA-N 1-(2-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Br PIMNFNXBTGPCIL-UHFFFAOYSA-N 0.000 description 1
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 1
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 1
- ORPVVAKYSXQCJI-UHFFFAOYSA-N 1-bromo-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Br ORPVVAKYSXQCJI-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- IZTPVMLLXOLWQB-UHFFFAOYSA-N CC1=CC=CC=C1Br.F.F.F Chemical compound CC1=CC=CC=C1Br.F.F.F IZTPVMLLXOLWQB-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- DGWFDTKFTGTOAF-UHFFFAOYSA-N P.Cl.Cl.Cl Chemical compound P.Cl.Cl.Cl DGWFDTKFTGTOAF-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004134 energy conservation Methods 0.000 description 1
- XXUJMEYKYHETBZ-UHFFFAOYSA-N ethyl 4-nitrophenyl ethylphosphonate Chemical compound CCOP(=O)(CC)OC1=CC=C([N+]([O-])=O)C=C1 XXUJMEYKYHETBZ-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- BISSQVWYQNHTIH-UHFFFAOYSA-N n-benzyl-n-phenylacetamide Chemical compound C=1C=CC=CC=1N(C(=O)C)CC1=CC=CC=C1 BISSQVWYQNHTIH-UHFFFAOYSA-N 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides an N-arylation method in an aqueous phase system, which is simple and convenient and environmentally friendly, and has mild reaction condition and economic process. The method comprises the following steps: taking aryl halide and amine as raw materials, and water as solvent, metallic copper, or oxide of copper, or cuprous salt or cupric salt as catalytic agent, and using adipic dihydrazide compound as a ligand to generate C-N coupling reaction; the reaction steps are as follows: adding catalyst, ligand, aryl halide, amine, alkali, surface active agent and water into a microwave reactor or a reaction vessel; reacting by stirring by adopting the mode of microwave assistant heating, or common heating bath heating or direct room temperature reaction; separating and purifying the reaction mixed liquor after the reaction is completed to obtain the N-arylation product. The method of the invention has the characteristics of simple operation, wide substrate application range, simple products which can be separated easily, high yield, economic process and environmental friendliness and the like, and takes water as solvent, has wide application range of the substrate, and has wide application prospects in preparation aspects of natural products, drugs and pesticides.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of N-arylation method.
Technical background
Arylamines is the important compound of a class, extensively is present in to have in the natural of physiologically active and the non-natural product, and the research that the C-N key is formed reaction attracts widespread attention always.
The Ullmann of carbon-nitrogen cross-coupling reaction is from reported first in 1903 existing history (Ley, S.V. for a long time so far; Thomas, A.W.Angew.Chem.Int.Ed.2003,42,5400 reach relevant quoted passage).Because this reaction is normally in high boiling polar solvent, carry out under as the condition of catalyzer at the copper powder of high temperature, catalytic amount or equivalent, thereby having long reaction time, the subsequent disposal of reaction is difficult, the not high drawback of reaction product complexity and reaction yield.Nineteen eighty-three, the people such as Migita have found that the earliest the C-N key of Pd catalysis forms reaction (Kosugi, M.; Kameyama, M.; Migita, T.Chem.Lett.1983,927), 1994, the C-N key that Buchwald and Hartwig have developed Pd catalysis simultaneously independently formed reaction ((a) Guram, A.S.; Buchwald, S.L.J.Am.Chem.Soc.1994,116,7901; (b) Paul, F.; Patt, J.; Hartwig, J.F.J.Am.Chem.Soc.1994,116,5969).Adopt the more traditional Ullmann reaction of C-N key formation reaction of Pd catalysis to have relatively gentleness of condition, reacting phase is to the advantage such as simple, need to use high boiling organic solvent but also exist, toxicity is larger, price is high, and to the shortcomings such as dependency of unstable and hypertoxic organophosphorus ligand, therefore, in recent years, the Ullmann of Cu catalysis reacts the very large development of having got back.The people's such as Buckwald patent PCT/US02/12785 (WO 02/085838) and Ley, S.V. and; Thomas, the summary of A.W. (Ley, S.V.; Thomas, A.W.Angew.Chem.Int.Ed.2003,42,5400) in introduced the formation method of the C-N key under the copper katalysis.By adding suitable part, use the mantoquita of catalytic amount, the Ullmann reaction can be carried out under comparatively gentle condition.Yet, no matter adopt which kind of metal catalyst, the N-arylation reaction of reporting in these documents is normally carried out in organic solvent.And all price is higher for the part majority that adopts, and is difficult to obtain.Therefore, inventing a kind of economy, environmental friendliness and the wide reaction process of suitable substrates scope is the objective requirement of current such reaction, and good application prospect will be arranged.
The people such as Pell ó n have reported the C-N linked reaction of copper catalysis in the aqueous solution ((a) Pell ó n, R.F.; Carrasco, R.; Rod é s, L.Synth.Comm.1993,23 (10), 1447; (b) Pell ó n, R.F.; Est é vez-Braun, A.; Docampo, M.L.; Mart í n, A.; Ravelo, A.G.Synlett 2005, (10), 1606), but only be confined to the ortho position with the aryl halides of carboxyl and the reaction of amine.The people such as Twieg have reported synthetic method (Lu, the Z. of arylamines in the aqueous solution take DMAE as part of cuprous iodide catalysis; Twieg, R.J.Tetrahedron Lett.2005,46,2997), but only be confined to aromatic halogenate and amino acid or with certain water miscible short-chain fat amine is arranged and with the reaction of the aliphatic amide of hydroxyl.Reported the linked reaction of aromatic halogenate and ammoniacal liquor or short-chain alkyl amine in the aqueous solution of catalysis of cupric sulphate in the European patent EP 0549263.But above-mentioned reaction all can only be carried out for specific compound, thereby can not promote the use of.And (Huang, X. are reacted in the formation of C-N key in the aqueous solution of the Pd catalysis of the people such as Buchwald report; Anderson, K.W.; Zim, D.; Jiang, L.; Klapars, A.; Buchwald, S.L.J.Am.Chem.Soc.2003,125,6653) then the cost because of catalyst system have defective.The applicant once proposed patent application 200610033067 and 200710026860, had overcome to a certain extent the shortcoming that exists in the conventional art C-N linked reaction method, but also had the too high shortcoming of part consumption.
The present invention is under National 863 high-tech plan class (2006AA09Z446) is subsidized, and the research that provides a kind of economy, gentleness, eco-friendly N-arylation method to carry out is provided.
Summary of the invention
The object of the present invention is to provide a kind of easy, reaction conditions is gentle, the N-arylation method of environmental friendliness, process economy, overcomes the shortcoming that exists in the C-N linked reaction method in the prior art.
The present invention is the formation method of C-N key in a kind of aqueous solution, take aryl halides and amine as raw material, with water as solvent, in the presence of alkali, reaction or employing traditional heating or Microwave-assisted firing under room temperature, add tensio-active agent, under transition metal-catalyzed condition, use hydrazide kind compound as the C-N linked reaction of part.
Innovative point of the present invention is: take the oxide compound of metallic copper or copper or cupprous salt or cupric salt as catalyzer, use to replace two hydrazide kind compounds as part, can reach preferably effect under the condition of less part consumption.
Involved reaction can adopt following reaction formula to represent among the present invention:
Wherein X-is selected from bromine or iodine.
R
1Be selected from the substituting group of 2-on the aromatic ring or 3-or 4-position, or two on the aromatic ring replaces or multi-substituent; Can be H, NO2 ,-CN ,-COOH ,-COOR, ethanoyl, alkyl, alkoxyl group, aryl, halogen, trifluoromethyl etc. but not only be confined to these substituting groups.
R
2NH
2Being selected from primary amine, can be aromatic amine, aliphatic amide; Comprise that specifically (substituting group is alkyl to cycloalkyl, benzyl, the substituted benzyl that contains straight or branched alkyl, C5-C7, alkoxyl group etc.) etc. Armeen, or contain the primary amine of aromatic substituent (aromatic substituent is benzene or with alkyl, the substituent benzene such as alkoxyl group).
Part is for replacing two hydrazide kind compounds, and its structural formula is:
Wherein R is alkyl or aromatic base; Optional from one of following: as to contain straight or branched alkyl (C1-C6), cycloalkyl, benzyl, benzyl substituting group (substituted alkyl, or contain aromatic substituent (aromatic substituent is benzene or with alkyl alkoxyl group, nitro etc.),, alkoxyl group, the substituent benzene such as nitro).
Concrete reaction process of the present invention is: catalyzer, part, aryl halides, amine, alkali, tensio-active agent and water are added in microwave reactor or the reaction vessel, adopt the mode stirring reaction of Microwave-assisted firing or common heating bath heating or direct room temperature reaction; After reaction finished, separating reaction mixed solution and purifying obtained N-arylation product.
The below further describes the inventive method:
(1) take water as reaction solvent, inexpensive, environmental friendliness;
(2) reaction can at room temperature be carried out, and the reaction times is 24-96h, is preferably 48-72h; The reaction heating can be adopted the mode of Microwave-assisted firing or common heating bath heating.During Microwave-assisted firing, temperature of reaction is 60-130 ℃, and the reaction times is 1-10min; Preferable reaction temperature is 100-130 ℃, reaction times 2-5min.During common heating bath heating, temperature of reaction is 50-100 ℃, and the reaction times is 1-24h; Preferable reaction temperature is 60-90 ℃, and the reaction times is 4-16h;
(3) reactant aryl halides can be that replace or non-substituted, and the mol ratio of aryl halides and amine is 1: 1 to 1: 5;
(4) described part is to replace two hydrazide kind compounds; The mol ratio of described part and catalyzer is 10: 1 to 1: 1;
(5) described catalyzer can be the oxide compound of metallic copper, copper, cupprous salt, cupric salt such as cupric oxide, Red copper oxide, copper sulfate, cupric nitrate, cupric chloride, cuprous chloride, cuprous iodide, cupric acetate etc. but be not limited only to that these are several, and the mol ratio of catalyzer and substrate aryl halides is 1: 40 to 1: 2.
(6) described alkali can be carbonate, phosphoric acid salt, fluorochemical, borate and the oxyhydroxide of basic metal or alkaline-earth metal or the compound that can be converted into respective compound in water; The mol ratio of alkali and substrate aryl halides is 1: 1 to 3: 1;
(7) employed tensio-active agent can be quaternary ammonium salts, season phosphonium salt class, dodecane sulfonate class, PEG class but not only be confined to these tensio-active agents; The mol ratio of tensio-active agent and substrate aryl halides is 1: 20 to 1: 1.
The characteristics such as that the inventive method has is simple to operate, wide application range of substrates, product simply are easy to separate, productive rate is high, process economy and environmental friendliness.And because the handiness of reaction conditions can according to actual needs, be selected the mode (reaction times is short) of room temperature reaction (energy-conservation, as be adapted to heat-labile substrate, but the reaction times to be relatively long) or employing Microwave-assisted firing accordingly.In addition, with water as reaction solvent, with the reacting phase ratio of the same type of reporting in the document, effectively improved the environment friendly of reaction, more conform to the requirement of Green Chemistry development, especially wide application range of substrates is having broad application prospects aspect the preparation of natural product, medicine and agricultural chemicals.
Embodiment
Below in conjunction with embodiment content of the present invention is described further.
Synthesizing of embodiment 1:N-p-methoxyphenyl aniline
With 2mg (0.025mmol) CuO, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 279mg (2.0mmol) aniline, 0.28mg (0.5mmol) KOH, 32mg (0.1mmol) TBAB, 5.0ml H
2O adds in the 50ml round-bottomed flask, stirring reaction 96h under the room temperature condition.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl aniline 83mg, yield 83%.
N-p-methoxyphenyl aniline:
1H NMR (300MHz, CDCl
3) δ: 7.26-7.19 (m, 2H), 7.10 (d, J=8.7,2H), 6.93-6.81 (m, 5H), 5.62 (br s, 1H), 3.81 (s, 3H); MS (ESI, m/z): 200[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.38 (d, J=6.3Hz, 6H), 3.81 (s, 6H), 4.05 (q, J=6.3Hz, 2H), 6.87 (d, J=8.4Hz, 4H), 7.25 (d, J=8.4Hz, 4H).MS(FAB
+，m/z)：387[M+H]
+。
Synthesizing of embodiment 2:N-phenylbenzylamine
With 1.1mg (0.0125mmol) CuCl, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 214mg (2.0mmol) benzylamine, 0.56mg (1mmol) KOH, 32mg (0.1mmol) TBAB, 2mlH
2O, 78mg (0.5mmol) bromobenzene adds in the 50ml round-bottomed flask stirring reaction 24h under the room temperature condition.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-phenylbenzylamine 46mg, yield 50%.
The N-phenylbenzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.42-7.41 (m, 7H), 6.81-6.68 (m, 3H), 4.38 (s, 2H), 4.07 (br s, 1H) .MS (ESI, m/z): 184[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.42 (d,, J=6.6Hz, 6H), 4.11 (q, J=6.6Hz, 2H), 7.27-7.38 (m, 10H).MS(EI，m/z)：326(M
+，4)，105(100)。
Embodiment 3:N-is synthetic to the acetyl phenylbenzylamine
With 47.5mg (0.25mmol) CuI, 104mg (0.25mmol) part, 0.1mg (0.5mmol) be to the acetyl bromobenzene, 214mg (2.0mmol) benzylamine, 212mg (1.0mmol) K
3PO
4, 94mg (0.25mmol) tetraphenylphosphonichloride chloride phosphorus, 5.0ml H
2O adds in the 50ml round-bottomed flask, stirring reaction 24h under 90 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through the silicagel column column chromatography for separation, gets N-to acetyl phenylaniline 56mg, yield 50%.
N-is to the acetyl phenylaniline:
1H NMR (400MHz, CDCl
3) δ: 7.83 (d, J=8.8,2H), 7.36-7.30 (m, 5H), 6.61-6.59 (d, J=8.8,2H), 4.41 (s, 2H), 2.49 (s, 3H) .ESI-MS:m/z=226[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.41 (d, J=6.6Hz, 6H), 4.24 (q, J=6.6Hz, 2H), 7.53 (d, J=8.4Hz, 4H), 8.21 (d, J=8.4Hz, 4H), 8.37 (brs, 2H).MS(EI，m/z)：416(M
+，9)，150(100)。
Synthesizing of embodiment 4:N-p-nitrophenyl aniline
With 3.1mg (0.0125mmol) CuSO
45H
2O, 104mg (0.125mmol) part, 100mg (0.5mmol) be to the nitro bromobenzene, 140mg (1.5mmol) aniline, 84mg (1.5mmol) KOH, 161mg (0.5mmol) TBAB, 10ml H
2O adds in the 50ml round-bottomed flask, reflux 10h.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (10: 1)] through the silicagel column column chromatography for separation, gets N-o-methyl-phenyl-benzylamine 138mg, yield 70%.
N-o-methyl-phenyl-benzylamine:
1H NMR (400MHz, CDCl
3) δ: 8.12 (d, J=9.2,2H), 7.39 (t, J=4.4,2H), 7.22-7.15 (m, 3H), 6.95 (d, J=9.2,2H), 6.30 (br s, 1H) .ESI-MS:m/z=215[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 4.03 (s, 4H), 7.31-7.39 (m, 10H).ESI-MS：m/z＝299[M+H]
+。
Synthesizing of embodiment 5:N-p-methoxyphenyl n-Butyl Amine 99
With 14mg (0.1mmol) Cu
2O, 54mg (0.2mmol) part, 100mg (0.5mmol) be to the methoxyl group iodobenzene, 118mg (2.5mmol) n-Butyl Amine 99,325mg (1.0mmol) Cs
2CO
3, 136mg (0.5mmol) SDS-Na, 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 10min under 100 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl n-Butyl Amine 99 45mg, yield 50%.
N-p-methoxyphenyl n-Butyl Amine 99:
1H NMR (400MHz, CDCl
3) δ: 6.81 (d, J=8.8,2H), 6.61 (d, J=8.8,2H), 3.76 (s, 3H), 3.10-3.06 (3H), 1.64-1.57 (m, 2H), 1.48-1.39 (m, 2H), 0.99-0.95 (t, 3H) .ESI-MS:m/z=180[M+H]
+
Part:
1H NMR (300MHz, DMSO-d
6) δ: 6.70-6.75 (m, 6H), 7.13-7.18 (m, 4H), 7.89 (d, J=3Hz, 2H), 10.67 (d, J=3Hz, 2H).MS(EI，m/z)：270(M
+，56)，93(100)。
Embodiment 6:N-p-methoxyphenyl is synthetic to monomethylaniline
With 12.8mg (0.2mmol) Cu, 51mg (0.2mmol) part, 187mg (0.5mmol) is to the methoxyl group bromobenzene, 53.5mg (0.5mmol) to monomethylaniline, 84mg (1.5mmol) KOH, 161mg (0.5mmol) TBAB, 10ml H
2O adds in the 50ml round-bottomed flask, reflux 12h.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets the N-p-methoxyphenyl to methylbenzene 129mg, yield 67%.
1H?NMR(400MHz，CDCl
3)δ：7.06-7.02(m，4H)，6.88-6.84(m，4H)，5.41(br?s，1H)，3.81(s，3H)，2.31(s，3H).ESI-MS：m/z＝214[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.48-1.83 (m, 16H), 3.45-3.52 (m, 2H).ESI-MS：m/z＝255[M+H]
+
Synthesizing of embodiment 7:N-rubigan benzylamine
With 2.3mg (0.0125mmol) Cu (NO
3)
2, 17.6mg (0.0625mmol) part, 96mg (0.5mmol) para chlorobromobenzene, 268mg (2.5mmol) benzylamine, 56mg (1.0mmol) KOH, PEG400 (0.2mL), 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 1min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-rubigan benzylamine 54mg, yield 50%.
N-rubigan benzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.37-7.26 (m, 5H), 7.14 (d, J=8.7,2H), 6.57 (d, J=8.4,2H), 4.32 (s, 2H), 4.09 (br s, 1H) .ESI-MS:m/z=218[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 1.15-1.90 (m, 20H), 2.77-2.85 (m, 2H).ESI-MS：m/z＝：283[M+H]
+
Synthesizing of embodiment 8:N-p-trifluoromethyl phenyl aniline
With 4.5mg (0.025mmol) Cu (OAc)
2, 36mg (0.125mmol) part, 112mg (0.5mmol) be to methyl bromobenzene trifluoride, 214mg (2.0mmol) benzylamine, 138mg (1.0mmol) K
2CO
3, 81mg (0.25mmol) TBAB, 1.5ml H
2O adds in the 8ml microwave reaction pipe, and 80W reacts 7min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1] through the silicagel column column chromatography for separation, gets N-p-trifluoromethylaniline 71mg, yield 70%.
The N-p-trifluoromethylaniline:
1H NMR (300MHz, CDCl
3) δ: 7.49 (d, J=6.3,2H), 7.10 (t, J=6.3,2H), 7.16 (d, J=5.7,2H), 7.08-7.03 (m, 5H), 5.90 (br s, 1H); ESI-MS:m/z=238[M+H]
+.
Part:
1H NMR (300MHz, CDCl
3) δ: 0.92-1.51 (m, 24H), 2.94-3.01 (m, 2H).ESI-MS：m/z＝287[M+H]
+
Embodiment 9:N-is synthetic to the ethylphenyl benzylamine
With 13.5mg (0.1mmol) CuCl
2, 15mg (0.1mmol) part 85mg (0.5mmol) is to 2 bromo toluene, 321mg (1.5mmol) benzylamine, 69mg (0.5mmol) K
2CO
3, 255mg (0.5mmol) n-hexadecyl three normal-butyl bromination phosphines, 2mlH
2O adds in the 8ml microwave reaction pipe, and 80W reacts 5min under 130 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-o-methyl-phenyl-benzylamine 69mg, yield 70%.
N-is to the ethylphenyl benzylamine:
1H NMR (300MHz, CDCl
3) δ: 7.34-7.17 (m, 5H), 7.06-7.01 (m, 2H), 6.64-6.54 (m, 2H), 4.32 (s, 2H), 3.80 (br s, 1H), 2.12 (s, 3H).
13C NMR (75MHz, CDCl
3) δ: 145.9,139.3,129.9,128.5,127.4,127.1,127.0,121.7,117.0,109.9,48.3,17.6.ESI-MS:m/z=198[M+H]
+
Part:
1H NMR (300MHz, CDCl
3) δ: 10.19 (br s, 2H), 4.99 (br s, 2H), 2.46 (s, 6H) .MS (EI, m/z): 146 (M
+, 80), 46 (100).
Synthesizing of embodiment 9:N-p-methoxyphenyl hexahydroaniline
With 2mg (0.025mmol) CuO, 48mg (0.125mmol) part, 96mg (0.5mmol) be to the methoxyl group bromobenzene, 198mg (2.0mmol) hexahydroaniline, 0.28mg (0.5mmol) KOH, 32mg (0.1mmol) TBAB, 2mlH
2O adds in the 8ml microwave reaction pipe, and 80W reacts 10min under 60 ℃ of conditions.After reaction stops, use ethyl acetate extraction, washing, the saturated common salt washing behind the anhydrous magnesium sulfate drying, is filtered, the underpressure distillation desolventizing, the reaction mixture that obtains is purified by [eluent: petrol ether/ethyl acetate (20: 1)] through the silicagel column column chromatography for separation, gets N-p-methoxyphenyl hexahydroaniline 75mg, yield 73%.
N-p-methoxyphenyl hexahydroaniline:
1H NMR (400MHz, CDCl
3) δ: 6.78 (d, J=8.8Hz, 2H), 6.58 (d, J=8.8Hz, 2H), (3.74 s, 3H), 3.20-3.13 (m, 1H), 2.06-2.02 (m, 2H), 1.78-1.73 (m, 3H), 1.38-1.11 (m, 5H) .ESI-MS:m/z=206[M+H]
+.
Part:
1H NMR (300MHz, CDCl
3) δ: 3.12-3.06 (m, 2H), 2.14-1.51 (m, 28H) .ESI-MS:m/z=387[M+H]
+..
Claims (4)
1. to replace the N-arylation method of two hydrazides in the aqueous phase system of part, take aryl halides and amine as raw material, it is characterized in that: with water as solvent, take the oxide compound of metallic copper or copper or cupprous salt or cupric salt as catalyzer, use to replace two hydrazide kind compounds and produce the C-N linked reaction as part; Reactions steps is: catalyzer, part, aryl halides, amine, alkali, tensio-active agent and water are added in microwave reactor or the reaction vessel, adopt the mode stirring reaction of Microwave-assisted firing or common heating bath heating or direct room temperature reaction; After reaction finished, separating reaction mixed solution and purifying obtained N-arylation product;
Described replacement two hydrazide kind compound structural formulas are:
Wherein R is alkyl or aromatic base, is selected from one of following: the straight or branched alkyl of C1-C6, cycloalkyl, benzyl or with alkyl, alkoxyl group, the benzyl of nitro substituent, phenyl or with alkyl, alkoxyl group, the phenyl of nitro substituent.
2. according to claim 1 to replace the N-arylation method of two hydrazides in the aqueous phase system of part, it is characterized in that: described reaction adopts following reaction formula to represent:
Wherein X-is selected from bromine or iodine;
R
1Be the substituting group of 2-on the aromatic ring or 3-or 4-position, or two on the aromatic ring replaces or multi-substituent; Be selected from one of following: H, NO2 ,-CN ,-COOH, ethanoyl, alkyl, alkoxyl group, aryl, halogen, trifluoromethyl;
R
2NH
2Be primary amine, be aromatic amine or aliphatic amide, be selected from one of following: the cycloalkyl of straight or branched alkyl, C5-C7 or contain the primary amine of aromatic substituent;
Part is for replacing two hydrazide kind compounds, and its structural formula is:
Wherein R is alkyl or aromatic base, is selected from one of following: the straight or branched alkyl of C1-C6, cycloalkyl, benzyl or with alkyl, alkoxyl group, the benzyl of nitro substituent, phenyl or with alkyl, alkoxyl group, the phenyl of nitro substituent;
Catalyzer is oxide compound or cupprous salt or cupric salt of metallic copper or copper;
The mol ratio of catalyzer and substrate aryl halides is 1: 40 to 1: 2; The mol ratio of part and catalyzer is 10:1 to 1:1.
3. according to claim 1 and 2 to replace the N-arylation method of hydrazides in the aqueous phase system of part, it is characterized in that: described catalyzer is selected from one of following; Metallic copper, cupric oxide, Red copper oxide, copper sulfate, cupric nitrate, cupric chloride, cuprous chloride, cuprous iodide, neutralized verdigris.
4. according to claim 1 and 2 to replace the N-arylation method of two hydrazides in the aqueous phase system of part, it is characterized in that: the mol ratio of aryl halides and amine is 1: 1 to 1: 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910040649 CN101691318B (en) | 2009-06-29 | 2009-06-29 | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910040649 CN101691318B (en) | 2009-06-29 | 2009-06-29 | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101691318A CN101691318A (en) | 2010-04-07 |
| CN101691318B true CN101691318B (en) | 2013-05-29 |
Family
ID=42080055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200910040649 Active CN101691318B (en) | 2009-06-29 | 2009-06-29 | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101691318B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102050687B (en) * | 2010-11-30 | 2014-04-23 | 中山大学 | Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system |
| CN102806104B (en) * | 2012-08-21 | 2015-01-21 | 浙江大学 | Catalyst for aqueous-phase preparation of indole nitrogen arylide and preparation method of indole nitrogen arylide |
| CN106883132B (en) * | 2017-01-18 | 2019-03-22 | 中山大学 | One kind replaces the copper that hydrazides is ligand to be catalyzed C-N coupling method with N, N- bis- |
| CN109456205B (en) * | 2018-12-17 | 2021-09-21 | 石河子大学 | N-arylation method in aqueous phase system by using substituted quinoline or isoquinoline hydrazide pyridine-N-oxide as ligand |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1803760A (en) * | 2006-01-19 | 2006-07-19 | 中山大学 | N-arylation process with hydrazone as ligand in aqueous phase system |
| CN1984872A (en) * | 2004-07-16 | 2007-06-20 | 帝斯曼知识产权资产管理有限公司 | Process for the preparation of an (hetero) arylamine |
| CN101012170A (en) * | 2007-02-09 | 2007-08-08 | 中山大学 | N-arylation method in water solution |
-
2009
- 2009-06-29 CN CN 200910040649 patent/CN101691318B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1984872A (en) * | 2004-07-16 | 2007-06-20 | 帝斯曼知识产权资产管理有限公司 | Process for the preparation of an (hetero) arylamine |
| CN1803760A (en) * | 2006-01-19 | 2006-07-19 | 中山大学 | N-arylation process with hydrazone as ligand in aqueous phase system |
| CN101012170A (en) * | 2007-02-09 | 2007-08-08 | 中山大学 | N-arylation method in water solution |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101691318A (en) | 2010-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102050687B (en) | Method for preparing aromatic primary amine by taking ammonia water as ammonia source in water phase system | |
| CN1914177B (en) | Optically active quaternary ammonium salt having axial asymmetry and process for producing alpha-amino acid and derivative thereof with the same | |
| Allen et al. | Metal-catalysed approaches to amide bond formation | |
| DE69929609T2 (en) | LIGANDS FOR METALS AND METAL-CATALYZED PROCESS | |
| JP5481476B2 (en) | Process for producing substituted biphenyls | |
| CN101691318B (en) | N-arylation method taking substituted adipic dihydrazide as ligand in aqueous phase system | |
| JP7023080B2 (en) | Method for producing aromatic compounds | |
| CN103408601A (en) | Heteronuclear bimetallic complexes having catalytic activity for the Suzuki reaction and preparation method thereof | |
| CN110483223A (en) | The method that pyridine palladium efficient catalytic prepares diaryl ketone compound | |
| CN101012170B (en) | N-arylation method in water solution | |
| CN101774874B (en) | N-arylating method using pyrrole-2-hydrazide compound as ligand in aqueous phase system | |
| Shi et al. | General rhodium-catalyzed oxidative cross-coupling reactions between anilines: synthesis of unsymmetrical 2, 2′-diaminobiaryls | |
| CN100336794C (en) | N-arylation process with hydrazone as ligand in aqueous phase system | |
| CN101654419A (en) | Preparation method of fluvoxamine maleate | |
| CN101890366A (en) | Cupric salt-containing catalyst system and application thereof | |
| CN103242371A (en) | Aryl-pyridine cyclic Pd-N heterocyclic carbene compound as well as preparation method and application thereof | |
| CN101851225B (en) | Method for synthesizing fludioxonil intermediate 4-aldehyde-2,2-difluorobenzodioxole | |
| CN110229085A (en) | Alcohol promotes imines and alkynes reductive coupling reaction to construct allylamine derivatives | |
| US6962999B2 (en) | Process for preparing unsymmetrical biaryls and alkylated aromatic compounds from arylnitriles | |
| CN103739417A (en) | Method for synthesizing aromatic primary amine in circulating water phase system | |
| CN101466718A (en) | C2-symmetrical bi-ruthenium dual-phosphine ligand and synthesizing method thereof | |
| CN110724047B (en) | Method for preparing aromatic carboxylic acid compound | |
| CN112679381A (en) | Method for synthesizing beta-ketonitrile and derivative thereof | |
| CN100491387C (en) | Ferrocenyl imidazoliny palladium compound, its preparation method and its uses in catalytic synthesis of coupling product | |
| JP4581132B2 (en) | A catalyst containing an amphiphilic organophosphorus compound and a transition metal complex, and a method for producing a biaryl compound using the catalyst. |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170828 Address after: 262714, No. 1187 Huang Hai Road, Bohai chemical industry park, Shouguang City, Shandong, Weifang province (sheep town) Patentee after: Shouguang Xintai Fine Chemical Co., Ltd. Address before: 510275 Xingang West Road, Guangdong, China, No. 135, No. Patentee before: Sun Yat-sen University |
|
| TR01 | Transfer of patent right |