CN102295497B - Synthesis method of halogenated aromatic hydrocarbon compound with water as solvent - Google Patents
Synthesis method of halogenated aromatic hydrocarbon compound with water as solvent Download PDFInfo
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- CN102295497B CN102295497B CN 201010217312 CN201010217312A CN102295497B CN 102295497 B CN102295497 B CN 102295497B CN 201010217312 CN201010217312 CN 201010217312 CN 201010217312 A CN201010217312 A CN 201010217312A CN 102295497 B CN102295497 B CN 102295497B
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 239000002904 solvent Substances 0.000 title abstract description 17
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 title abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 56
- -1 aryl boric acid Chemical compound 0.000 claims abstract description 54
- 239000003054 catalyst Substances 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000004327 boric acid Substances 0.000 claims abstract description 28
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 6
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims abstract description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims abstract description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims abstract description 4
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims abstract description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 4
- 229940045803 cuprous chloride Drugs 0.000 claims abstract description 4
- 229910052792 caesium Inorganic materials 0.000 claims abstract description 3
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 3
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 3
- 239000010949 copper Substances 0.000 claims description 22
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 15
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 13
- 229910052802 copper Inorganic materials 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 229910052728 basic metal Inorganic materials 0.000 claims description 5
- 150000003818 basic metals Chemical group 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical group C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052701 rubidium Inorganic materials 0.000 claims description 2
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 229960004643 cupric oxide Drugs 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 7
- 238000006555 catalytic reaction Methods 0.000 abstract description 7
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 229940112669 cuprous oxide Drugs 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000011734 sodium Substances 0.000 abstract description 2
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 abstract 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 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 abstract 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract 1
- 229910052783 alkali metal Inorganic materials 0.000 abstract 1
- 150000001340 alkali metals Chemical class 0.000 abstract 1
- 150000001447 alkali salts Chemical class 0.000 abstract 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 abstract 1
- 150000004820 halides Chemical class 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000011591 potassium Substances 0.000 abstract 1
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 39
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 229960004839 potassium iodide Drugs 0.000 description 18
- 235000007715 potassium iodide Nutrition 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 17
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 14
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 14
- 239000011630 iodine Substances 0.000 description 13
- 238000010189 synthetic method Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ITJSVDCZHCYXQE-UHFFFAOYSA-N toluene;hydroiodide Chemical compound I.CC1=CC=CC=C1 ITJSVDCZHCYXQE-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical group BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 description 3
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 3
- CBYAZOKPJYBCHE-UHFFFAOYSA-N 1-iodo-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(I)=C1 CBYAZOKPJYBCHE-UHFFFAOYSA-N 0.000 description 3
- KVBWBCRPWVKFQT-UHFFFAOYSA-N 3-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(I)=C1 KVBWBCRPWVKFQT-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- NDZXVMFFUZCSMU-UHFFFAOYSA-N C(C1=CC=CC=C1)=O.[I] Chemical compound C(C1=CC=CC=C1)=O.[I] NDZXVMFFUZCSMU-UHFFFAOYSA-N 0.000 description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical group [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000006193 diazotization reaction Methods 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical class COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000005865 C2-C10alkynyl group Chemical group 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UOZDOLIXBYLRAC-UHFFFAOYSA-L [2-hydroxy-3-(trimethylazaniumyl)propyl]-trimethylazanium;diiodide Chemical compound [I-].[I-].C[N+](C)(C)CC(O)C[N+](C)(C)C UOZDOLIXBYLRAC-UHFFFAOYSA-L 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- BIVHHENFZSOWCE-UHFFFAOYSA-N boric acid;bromobenzene Chemical group OB(O)O.BrC1=CC=CC=C1 BIVHHENFZSOWCE-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- QKSIFUGZHOUETI-UHFFFAOYSA-N copper;azane Chemical compound N.N.N.N.[Cu+2] QKSIFUGZHOUETI-UHFFFAOYSA-N 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000005171 halobenzenes Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- CJBOGZJHBWVYST-UHFFFAOYSA-N B(O)(O)O.ClC1=CC=C(C=C1)Cl Chemical compound B(O)(O)O.ClC1=CC=C(C=C1)Cl CJBOGZJHBWVYST-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- YVKOUANNKYWVHL-UHFFFAOYSA-N C1=CC=CC2=CC=CC=C12.[I] Chemical compound C1=CC=CC2=CC=CC=C12.[I] YVKOUANNKYWVHL-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000005749 Copper compound Substances 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001454 anthracenes Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- OOPSAZSKOMIGFX-UHFFFAOYSA-N boric acid;toluene Chemical compound OB(O)O.CC1=CC=CC=C1 OOPSAZSKOMIGFX-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- RCTYPNKXASFOBE-UHFFFAOYSA-M chloromercury Chemical compound [Hg]Cl RCTYPNKXASFOBE-UHFFFAOYSA-M 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- KFIFDKLIFPYSAZ-UHFFFAOYSA-N formyloxy(phenyl)borinic acid Chemical compound O=COB(O)C1=CC=CC=C1 KFIFDKLIFPYSAZ-UHFFFAOYSA-N 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000013462 industrial intermediate Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical group IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LBBMOAOCCQOIAQ-UHFFFAOYSA-N methoxy(phenyl)borinic acid Chemical compound COB(O)C1=CC=CC=C1 LBBMOAOCCQOIAQ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a synthesis method of a halogenated aromatic hydrocarbon compound with water as a solvent. The method is characterized in that the halogenated aromatic hydrocarbon compound is efficiently synthesized at the reaction temperature of about 15-25 DGE C under the reaction conditions of room temperature and normal pressure based on aryl boric acid as a raw material, water as the solvent, alkali metal (containing sodium, potassium, cesium and the like) halide as a halogen source, cuprous oxide, cuprous iodide, cuprous bromide or cuprous chloride and the like as a catalyst and ammonia water as a ligand. Compared with the conventional halobenzene compound synthesis method, the synthesis method disclosed by the invention has the obvious advantages that based on the available aryl boric acid compound, cheapest water is used as the solvent, low-cost cuprous oxide is used as the catalyst, reaction conditions are mild, environmental pollution is less, the generated halobenzene compound has high yield and high tolerance on multiple functional groups on an aromatic ring, separation and purification are convenient, and the like; and simultaneously, after the product is extracted, and a catalytic reaction can be cycled after quantitative alkali salt is added in a reaction system.
Description
Technical field
The present invention relates to the synthetic preparation of class Chemicals, relate more specifically to the synthetic method of haloarene compounds.
Background technology
Haloarene compounds, for example the iodo arene compounds is important industrial chemicals and intermediate.Take the most common iodobenzene as example, the relative bromobenzene of iodobenzene, chlorobenzene has higher chemically reactive, therefore catalysis C-C be bonded to the reaction of C-heteroatoms bonding in have widely and use.Industrial, iodobenzene is to survey the refractive index reference liquid, can be used for organic synthesis, produces liquid crystal material, medical material intermediate etc.
The iodobenzene industrial production is mainly that aniline is through diazotization, substitution method.30% hydrochloric acid, aniline are added to the water, stir and be cooled to 2 ℃, slowly drip sodium nitrite solution, control temperature and be no more than 12 ℃.When dripping the last part sodium nitrite solution, with the potassium iodide starch test paper test, be blue for reaction end, get diazotization liquid.Liquor kalii iodide is added in diazotization liquid several times, emit nitrogen this moment, place 2h, till overflowing without nitrogen.After cooling, divide and remove upper water solution.Adding 10% sodium hydroxide solution, to make reaction solution to pH value be 14.Carry out wet distillation, the distillate branch vibration layer, 184-188 ℃ of cut collected in dry rear normal pressure fractionation, is iodobenzene, yield 77%.
The greatest problem of this reaction is that condition is controlled comparatively strict, azo-compound easily decomposes under the condition that temperature raises, and this reaction simultaneously is lower to the tolerance of substituted radical on phenyl ring, so the iodobenzene of some special groups is difficult to make, as 3-methoxyl group iodobenzene, 2-iodine naphthalene etc.
Another method is to use benzene and iodine chloride reaction, and in this method, iodine chloride is more difficult to get, and is simultaneously equally very low to the substituent tolerance on aromatic ring in reaction process, can't obtain some with other substituent iodo arene compounds.
Some other method is used some catalyzer such as CrO
3, HgCl
2,, Ag
2SO
4Deng acid solution catalyze and synthesize the iodo arene compounds.
The iodo arene compounds synthetic method of these existing routines, not only needing organic solvent is catalyzer as solvent and precious metal, and the common comparatively reaction conditions (low temperature) of harshness that needs, and lower to substituent tolerance on phenyl ring in reaction, can't obtain some specific iodobenzene compound.
Therefore at present still need a kind of reaction raw materials be simple and easy to, reaction conditions is gentle and environmentally friendly, productive rate is high, the synthetic method of the haloarene compounds (especially iodo arene compounds) high to the substituted radical tolerance.
Summary of the invention
A kind of method that the purpose of this invention is to provide synthesizing halogen aromatic hydroxy compound.
The method of synthesizing halogen aromatic hydroxy compound provided by the present invention, under the condition that oxygen, copper catalyst and ammoniacal liquor exist, make aryl boric acid compound and halogen MX carry out substitution reaction in water and form corresponding haloarene compounds, wherein the M in MX represents basic metal or alkaline-earth metal, and X represents F, Cl, Br or I.
In the present invention, " haloarene compounds " have those skilled in the art the implication usually understood, namely contain the compound with the direct-connected aromatic ring structure of halogen (being F, Cl, Br, I), the various derivatives after for example iodobenzene, iodine naphthalene, chlorobenzene, bromobenzene or its are substituted.
In the present invention, " aryl boric acid compound " have those skilled in the art the implication usually understood, namely contain with boric acid on the compound of the direct-connected aromatic ring structure of boron atom, the various derivatives after such as phenylo boric acid, adjacent bromobenzene boric acid etc. or its are substituted.
Synthetic method of the present invention is a kind of universal method, be suitable for synthetic various haloarene compounds and derivative, therefore multiple functional group on aromatic ring is had high tolerance, and in fact there is no particular restriction to the substituent number in haloarene compounds and derivative and kind.Correspondingly, also there is no particular restriction to the substituent number in the aryl boric acid compound and kind.
In a concrete embodiment, the invention provides a kind of method of synthesizing as shown in the formula the haloarene compounds of (I);
Formula (I)
Wherein, X represents F, Cl, Br or I, and R represents to be connected to 0,1,2,3,4 or 5 substituting group on phenyl ring, and each R represents to be selected from C independently of one another
1-C
20Alkyl (preferred C
1-C
10Alkyl, more preferably C
1-C
6Alkyl), C
2-C
20Thiazolinyl (preferred C
2-C
10Thiazolinyl, more preferably C
2-C
6Thiazolinyl), C
2-C
20Alkynyl (preferred C
2-C
10Alkynyl, more preferably C
2-C
6Alkynyl), C
6-C
20Aryl (preferred C
6-C
10Aryl), halogen atom ,-OH ,-NO
2,-NH
2,-NHR ' ,-C (=O) OR ' ,-NHC (=O) R ' ,-OR ' ,-C (=O) R ' or HOR "-substituting group (each substituting group is further replaced by other substituting group alternatively, and is as described below), wherein R ' is H, C
1-C
6Alkyl, C
2-C
6Thiazolinyl, C
2-C
6Alkynyl, phenyl or benzyl, R " be C
1-C
6Alkylidene group, C
2-C
6Alkenylene, C
2-C
6Alkynylene;
The method of the haloarene compounds of preparation formula (I) is included under the existence of oxygen, copper catalyst, ammoniacal liquor, aryl boric acid compound and halide salt MX as shown in the formula (II) carry out the haloarene compounds that substitution reaction forms corresponding formula (I) in water
Formula (II)
The definition cotype (I) of the substituent R in formula (II), the M in MX represents that basic metal or alkaline-earth metal and X represent F, Cl, Br or I.
Synthetic method of the present invention need to be carried out under the existence of oxygen, for example carries out in air.Found that protection of inert gas or vacuum environment are unfavorable for the carrying out that reacts, perhaps the carrying out of even complete blocking reaction.
Synthetic method of the present invention can represent with following reaction equation (take iodo aromatic hydrocarbons as example):
Those skilled in the art understand: the definition of substituent R above-mentioned is broad sense, itself can be unsubstituted or is selected from such as C
1-C
10Alkyl (preferred C
1-C
6Alkyl), C
2-C
10Thiazolinyl (preferred C
2-C
6Thiazolinyl), C
2-C
10Alkynyl (preferred C
2-C
6Alkynyl), C
6-C
10Aryl, halogen atom ,-OH ,-NO
2,-NH
2,-NHR ' ,-C (=O) OR ' ,-NHC (=O) R ' ,-OR ' or-C (=O) at least one substituting group of R ' replaces (R ' definition the same).This specification sheets represents when being limited with carbonatoms before organic group: the carbonatoms of this group can be limit thereon, the arbitrary integer in lower range." C for example
1-C
20" represent that carbonatoms can be 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 or 20; " C
2-C
20" represent that carbonatoms can be 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 or 20; " C
6-C
20" represent that carbonatoms can be 6,7,8,9,10,11,12,13,14,15,16,17,18,19 or 20.Other C
1-C
10, C
1-C
6, C
2-C
6Deng having similar implication.
The number of substituent R above-mentioned can be 0,1,2,3,4,5, is preferably 0,1,2 or 3, more preferably 0,1 or 2.The number of R is 0 o'clock, and formula (1I) represents unsubstituted halobenzene, and formula (1I) represents unsubstituted phenylo boric acid.
Containing in the substituent situation that (contains 2) more than 2, thereby can linking together into ring, two substituent R condense with phenyl ring.For example, phenyl ring can form naphthalene nucleus, anthracene nucleus, benzoglyoxaline, benzo pyridine, benzopyrrole, cumarone benzene, benzo tetrahydrofuran (THF) etc. with two substituent R.
Obviously, above-named substituent R is not to be restrictive, and the situation of other substituent R of clearly not expressing has also been contained in the present invention.
Be applicable to copper catalyst of the present invention and comprise various mantoquitas and cuprous salt (comprising organic acid salt and inorganic acid salt), copper oxide or cuprous oxide compound, copper alkali or cuprous alkali, copper or cuprous organometallic compound.Concrete catalyst type is unimportant, because the present invention mainly utilizes copper-ammonia complex performance katalysis, thus importantly to there be metallic copper atom (ion) in catalyzer, and the type of gegenion is not very crucial.Preferably cuprous catalysis agent, especially preferred cuprous salt or Red copper oxide, for example cuprous iodide, cuprous bromide or cuprous chloride are because these materials are cheap and easy to get and catalytic activity is higher.
The present invention carries out in the system take water as solvent.If necessary, also can have extra organic solvent in system, but consider from environmental protection, productive rate equal angles, preferably not have other solvent, namely only with water as solvent.
Synthetic method of the present invention needs NH
3As the cuprous part of metal in catalyzer (L), auxiliary cuprous catalysis agent performance katalysis, thus effectively improve productive rate.Because reaction system is water-based, so NH in fact
3With ammoniacal liquor (NH
3-H
2O) form is present in reaction system.Can pass into gaseous state NH in reaction system when synthesizing
3, but more preferably directly use ammoniacal liquor (NH
3-H
2O), because the latter more easily obtains.
Preferably, the M in MX represents to be selected from the basic metal of Li, Na, K, Rb or Cs.
The temperature of reaction of method of the present invention can be determined according to actual needs voluntarily by the technician, but be generally 10-30 ℃ between, between preferred approximately 15-25 ℃, more preferably from about between 18-22 ℃.
The pressure of method of the present invention is not crucial, usually gets final product under normal pressure.
The reaction times of method of the present invention can be determined by the technician as required voluntarily according to reactant character, and a few hours are to a couple of days usually, for example approximately 24-48 hour.
In addition, (first prepare copper-ammino and close catalyst system, then it is joined in reaction system) when the contriver unexpectedly finds method proceed step by step of the present invention, productive rate is higher.At this moment, method comprises two independently steps:
1) under oxygen exists, copper catalyst and ammoniacal liquor are mixed;
2) with step 1) catalyst system of gained joins in the water that contains aryl boric acid compound and halogen MX, carries out substitution reaction.
Obviously, method of the present invention can also comprise the extra step such as necessary pre-treatment, aftertreatment.
The order of addition of various materials and concrete reactions steps can be adjusted according to actual needs by those skilled in the art.For example, when the laboratory middle and small scale reacts, can carry out as follows (take iodo aromatic hydrocarbons as example):
(1) in being housed, the Schlenk of magnetic stick (Shi Lanke) test tube adds cuprous catalysis agent (for example Red copper oxide, cuprous iodide, cuprous bromide or cuprous chloride), part ammoniacal liquor, the aryl boric acid compound of formula (II), iodized salt MI, normal temperature, react reasonable time under the condition that air exists, several hours or several days, as (24-48h);
(2) after reaction is completed, carry out according to a conventional method aftertreatment and purification.For example, first reaction mixture is used the dichloromethane solution extraction, use the aqueous solution of alkali MOH repeatedly to wash extraction liquid, fling at last methylene dichloride and can obtain pure iodo arene compounds.
Method of the present invention is not only applicable to the laboratory and prepares on a small scale, is suitable for the large-scale industrialization production in chemical plant yet.Concrete reaction parameter when large-scale industrialization is produced can be determined by normal experiment by those skilled in the art.
This shows, the aryl boric acid compound of method of the present invention from being easy to get as solvent, adopts cheap cuprous compound as catalyzer with the most cheap water, under the reaction conditions of gentleness, generates haloarene compounds with high yield.Compare with the halobenzene class synthetic method of routine, method of the present invention have reaction raw materials be easy to get, minimum as the solvent environmental pollution with water, the multiple functional group on aromatic ring is had the clear superiorities such as high tolerance, productive rate is high, the product separation purifying is simple and convenient.Also unexpectedly find in addition: the present invention's catalyst system used does not need special purifying treatment just can recycle after reaction is completed, namely after reaction product is extracted away from reaction system, after mother liquor added quantitative reaction thing (halogen and aryl boric acid), reaction can repeat.Method of the present invention can be widely used in the field such as the medicine, polymkeric substance, natural product of industry member and academia synthetic.
Embodiment
The below specifically describes synthetic method of the present invention.Should be noted that description given here and embodiment are only in order to describe the specific embodiment of the present invention, to make the technician be more readily understood the present invention, they are not to be intended to limit scope of the present invention.
Also note that each preferred technical characterictic of above-mentioned the inventive method and each the concrete technical characterictic in following specifically described embodiment can combine, the various combinations of all these technical characterictics, all fallen within the scope of the invention as all numerical ranges of bound etc. by the concrete disclosed numerical value of the present invention.
Raw material used in following specific embodiment, CuI and CuBr are available from Alfa Aesar company, Cu
2O is available from Shanghai diligent work inorganic salt company limited, and phenylo boric acid is bought in Beijing coupling Science and Technology Ltd..Other reagent, except specializing, all available from Sigma-Aldrich Inc., each reagent adopts means well known in the art to carry out using after purifying in case of necessity.
1H NMR and
13C NMR all adopts NEC ECA600 instrument to measure.Probe temperature is room temperature, in be designated as TMS, when solvent is deuterochloroform, choose reference:
1H NMR:TMS is 0.00ppm, CHCl
3Be 7.24ppm;
13C NMR:CDCl
3Be 77.0ppm; Solvent is deuterium during for DMSO:
1H NMR:TMS is 0.00ppm, and DMSO is 2.50ppm;
13C NMR:DMSO is 40.0ppm.ESI-MS adopts the BrukerESQYIRE-LC mass spectrograph to measure.
Cu
2O/NH
3-H
2The preparation of O catalyst system:
Take 3g Cu
2O dissolves in 20mL 25%NH
3-H
2In O, at room temperature stir 15min, the standing supernatant liquid of getting is as the Cu that is used for following each embodiment
2O/NH
3Catalyst system.
Embodiment 1, synthetic iodobenzene
In being housed, the round-bottomed flask of magnetic stick adds Cu
2O/NH
3Catalyst system 0.2mL, phenylo boric acid 122mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains iodobenzene 167mg through concentrated, and productive rate is 82%.
The product iodobenzene:
1H NMR (CDCl
3, 600MHz) δ 7.69 (d, 2H, J=7.6Hz), 7.32 (t, 1H, J=7.6Hz), 7.09 (t, 2H, J=7.6Hz).
13C NMR (CDCl
3, 125MHz) δ 137.4,130.2,127.4,94.4.EI-MS[M]
+M/z 204.0.
Embodiment 2, synthetic adjacent bromo-iodobenzene
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, adjacent bromobenzene boric acid 200mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains adjacent bromo-iodobenzene 175mg through concentrated, and productive rate is 62%.
Adjacent bromo-iodobenzene: 1H NMR (CDCl3, the 600MHz) δ 7.83 (d, 1H, J=7.6Hz) of product, (7.61 d, 1H, J=7.6Hz), 7.20 (t, 1H, J=7.6Hz), 6.98 (t, 1H, J=7.6Hz) .13C NMR (CDCl3,125MHz) δ 140.4,132.9,129.8,129.5,128.5,101.3.EI-MS[M]+m/z 281.9,283.9.
Embodiment 3, synthetic 2,5-, two chloroiodobenzones
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 2,5-dichlorobenzene boric acid 190.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 2,5-, two chloroiodobenzone 218mg through concentrated, and productive rate is 80%.
Product 2,5-two chloroiodobenzones:
1H NMR (CDCl
3, 600MHz) δ 7.84 (d, 1H, J=2.1Hz), 7.35 (d, 1H, J=8.3Hz), 7.26 (dd, 2H, J=8.3Hz, 2.06Hz).
13C NMR (CDCl
3, 125MHz) δ 139.5,137.2,132.9,129.8,129.64,98.4.EI-MS[M]
+M/z 271.9.
Embodiment 4, synthetic between chloroiodobenzone
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, m-chloro phenylo boric acid 156.3mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains a chloroiodobenzone 202mg through concentrated, and productive rate is 85%.
Chloroiodobenzone between product:
1H NMR (CDCl
3, 600MHz) δ 7.72 (s, 1H), 7.59 (d, 1H, J=8.3Hz), 7.32 (d, 1H, J=8.3Hz), 7.03 (t, 1H, J=8.3Hz).
13C NMR (CDCl
3, 125MHz) δ 137.2,135.76,135.1,131.1,128.1,94.2.EI-MS[M]
+M/z 237.9.
Embodiment 5,4-fluorine iodobenzene
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 4-fluorobenzoic boric acid 160.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 4-fluorine iodobenzene 182mg through concentrated, and productive rate is 82%.
Product 4-fluorine iodobenzene:
1H NMR (CDCl
3, 600MHz) δ 7.63 (dd, 2H), 6.83 (t, 2H, J=8.2Hz).
13C NMR (CDCl
3, 125MHz) δ 163.5,161.9,139.0,138.9,117.8,117.7,86.9.EI-MS[M]
+M/z 222.0.
Embodiment 6,3-iodonitrobenzene
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 3-oil of mirbane boric acid 166.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 3-iodonitrobenzene 209mg through concentrated, and productive rate is 84%.
Product 3-iodonitrobenzene:
1H NMR (CDCl
3, 600MHz) δ 8.56 (s, 1H), 8.21 (d, 1H, J=8.3Hz), 8.03 (d, 1H, J=8.3Hz), 7.30 (t, 1H, J=8.3Hz).
13C NMR (CDCl
3, 125MHz) δ 148.6,143.6,132.51,130.8,122.8,93.6.EI-MS[M]
+M/z 249.0.
Embodiment 7, synthetic 3-iodanisol
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 3-methoxyphenylboronic acid 135.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 3-iodanisol 173mg through concentrated, and productive rate is 74%.
Product 3-iodanisol:
1H NMR (CDCl
3, 600MHz) δ 7.27 (d, 1H, J=7.6Hz), 6.98 (dd, 1H, J=7.6Hz, 8.2Hz), 6.85 (dd, 1H, J=8.2Hz, 7.6Hz).
13C NMR (CDCl
3, 125MHz) δ 160.2,130.9,129.9,123.1,113.9,94.5,55.5.EI-MS[M]
+M/z 234.0.
Embodiment 8, synthetic to toluene iodide
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, to methylphenylboronic acid 135.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains toluene iodide 179mg through concentrated, and productive rate is 82%.
Product is to toluene iodide:
1H NMR (CDCl
3, 600MHz) δ 7.55 (d, 2H, J=4.1Hz), 6.91 (d, 2H, J=4.1Hz), 2.27 (s, 3H).
13C NMR (CDCl
3, 125MHz) δ 137.5,137.2,131.2,90.2.EI-MS[M]
+M/z 218.0.
Embodiment 9, synthetic adjacent toluene iodide
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, o-methyl-benzene boric acid 135.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains adjacent toluene iodide 176mg through concentrated, and productive rate is 81%.
The adjacent toluene iodide of product:
1H NMR (CDCl
3, 600MHz) δ 7.81 (d, 1H, J=7.6Hz), 7.24 (d, 2H, J=4.1Hz), 6.86 (m, 1H).
13C NMR (CDCl
3, 125MHz) δ 141.3,138.9,129.7,128.1,127.4,101.1,28.1.EI-MS[M]
+M/z 217.9.
Embodiment 10, synthetic 1-iodine naphthalene
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 1-naphthalene boronic acids 171.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 1-iodine naphthalene 216mg through concentrated, and productive rate is 85%.
Product 1-iodine naphthalene:
1H NMR (CDCl
3, 600MHz) δ 8.08 (d, 2H, J=8.3Hz), 7.84 (d, 1H, 8.3Hz), 7.77 (d, 1H, J=8.3Hz), 7.58 (t, 1H, J=8.3Hz), 7.52 (t, 1H, J=8.3Hz), 7.18 (t, 1H, J=8.3Hz).
13C NMR (CDCl
3, 125MHz) δ 137.5,134.5,134.2,132.2,129.1,128.7,127.8,126.9,126.8,99.7.EI-MS[M]
+M/z 254.0.
Embodiment 11,
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 2-naphthalene boronic acids 200mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 2-iodine naphthalene 221mg through concentrated, and productive rate is 87%.
Product 2-iodine naphthalene:
1H NMR (CDCl
3, 600MHz) δ 8.23 (s, 1H), 7.78 (d, 1H, 3.4Hz), 7.77 (dd, 1H, J=3.5Hz), 7.70 (m, 2H, J=8.9Hz, 6.24Hz, 3.5Hz), (7.55 d, 1H, J=8.9Hz), 7.47 (dd, 2H, J=3.5Hz, 6.2Hz).
13C NMR (CDCl
3, 125MHz) δ 136.7,135.1,134.5,132.2,129.6,127.9,126.9,126.6,125.89,91.5.EI-MS[M]
+M/z 254.0.
Embodiment 12, synthetic 4-iodobenzene methyl alcohol
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 4-methanol-based phenylo boric acid 151.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 4-iodobenzene methyl alcohol 218mg through concentrated, and productive rate is 93%.
Product 4-iodobenzene methyl alcohol:
1H NMR (CDCl
3, 600MHz) δ 7.68 (d, 2H, J=8.3Hz), 7.11 (d, 2H, J=8.3Hz), 4.69 (s, 2H).
13C NMR (CDCl
3, 125MHz) δ 140.5,137.7,129.0,128.9,93.1,64.8.EI-MS[M]
+M/z 234.0.
Embodiment 13, synthetic to benzaldehyde iodine
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, to formylphenylboronic acid 149.8mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains benzaldehyde iodine 193mg through concentrated, and productive rate is 83%.
Product is to benzaldehyde iodine:
1H NMR (CDCl
3, 600MHz) δ 9.96 (s, 1H), 7.92 (d, 2H, J=8.1Hz), 7.59 (d, 2H, 8.1Hz).
13C NMR (CDCl
3, 125MHz) δ 191.5,138.5,138.5,135.6,130.9,130.9,102.9.EI-MS[M]
+M/z 232.0.
Embodiment 14, synthetic adjacent 2-methoxyl group-5-benzaldehyde iodine
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 3-formyl radical-4-methoxyphenylboronic acid 180mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains adjacent 2-methoxyl group-5-benzaldehyde iodine 220mg through concentrated, and productive rate is 84%.
Product 2-methoxyl group-5-benzaldehyde iodine:
1H NMR (CDCl
3, 600MHz) δ 10.3 (s, 1H), 8.09 (d, 1H, 2.0Hz), 7.82 (dd, 2H, J=2.0Hz, 8.9Hz), 6.78 (d, 2H, J=8.9Hz), 3.92 (s, 3H).
13C NMR (CDCl
3, 125MHz) δ 188.4,166.5,144.2,137.1,126.6,114.2,83.1,56.0.EI-MS[M]
+M/z262.0.
Embodiment 15, synthetic 4-iodo-benzoic acid methyl esters
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 4-methoxyphenylboronic acid 180mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 4-iodo-benzoic acid methyl esters 199mg through concentrated, and productive rate is 76%.
Product 4-iodo-benzoic acid methyl esters:
1H NMR (CDCl
3, 600MHz) δ 7.80 (d, 2H, J=8.2Hz), 7.74 (d, 2H, 8.2Hz), 3.91 (s, 3H).
13C NMR (CDCl
3, 125MHz) δ 166.7,137.8,131.1,129.7,100.8,52.4.EI-MS[M]
+M/z 262.0.
Embodiment 16, synthetic m-iodobenzoic acid
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, a carboxyl phenylo boric acid 200mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains m-iodobenzoic acid 148mg through concentrated, and productive rate is 60%.
The product m-iodobenzoic acid:
1H NMR (DMSO-d
6, 600MHz) δ 13.23 (s, 1H), 8.23 (s, 1H), 7.98 (d, 1H, J=8.3Hz), 7.94 (d, 1H, J=7.6Hz), 7.31 (dd, 1H, J=8.3Hz, 7.56Hz).
13C NMR (DMSO-d
6, 125MHz) δ 165.4,140.8,137.1,132.3,130.3,128.0,94.1.ESI-MS[M+H]
+M/z 247.04.
Embodiment 17, synthetic 4-iodine diphenylene-oxide
In being housed, the round-bottomed flask of magnetic stick adds Red copper oxide/NH
3Catalyst system 0.2mL, 4-diphenylene-oxide phenylo boric acid 200mg, the water of potassiumiodide 0.830g and 2mL.At room temperature, open system was reacted 24 hours.After reaction was completed, adding 1.5mL concentration was the sodium hydroxide solution of 2mol/L, extracted 3 times with methylene dichloride, each 2mL, and the organic phase of merging obtains 4-iodine diphenylene-oxide 223mg through concentrated, and productive rate is 76%.
Product 4-iodine diphenylene-oxide:
1H NMR (CDCl
3, 600MHz) δ 7.91 (d, 1H, J=8.2Hz), 7.89 (d, 1H, J=7.6Hz), 7.80 (d, 1H, J=8.2Hz), 7.65 (d, 1H, J=8.2Hz), (7.48 dd, 1H, J=8.2Hz, 7.6Hz), (7.36 dd, 1H, J=8.2Hz, 7.6Hz), (7.09 dd, 1H, J=7.6Hz, 8.2Hz).
13C NMR (CDCl
3, 125MHz) δ 156.4,155.7,135.9,127.7,124.6,124.5,124.4,123.2,121.1,120.5,112.1,75.4.EI-MS[M]
+M/z 294.0.
Embodiment 18, synthetic iodobenzene
Undertaken by the described step of embodiment 1, use CuI/NH
3As catalyzer, in 24 hours afterreaction systems, the productive rate of iodobenzene is 70%.
Above embodiment 18 shows that other cuprous catalysis agent also is applicable to method of the present invention.
Embodiment 19, synthetic iodobenzene
Undertaken by the described step of embodiment 1, use Cu (OAc)
2/ NH
3As catalyzer, in 24 hours afterreaction systems, the productive rate of iodobenzene is 62%.
Embodiment 20, synthetic iodobenzene
Undertaken by the described step of embodiment 1, use NaI as propiodal, after 24 hours, the productive rate of iodobenzene is 78%.
Embodiment 20 shows can use other propiodal, the preparation iodobenzene.
Embodiment 21, synthetic iodobenzene
Undertaken by the described step of embodiment 1, but do not carry out the catalyst system pre-treatment, be about to the Cu of aequum
2O and 0.2mLNH
3-H
2O directly adds reaction system as catalyzer, and after 24 hours, the productive rate of iodobenzene is 48%.
Embodiment 1,21 shows that method of the present invention can carry out with the form of " single stage method " or " two-step approach ", can obtain required product, and still " two-step approach " is more preferred.The contriver infers (but the present invention is not subject to concrete theoretical explanation): when catalyst system was carried out pre-treatment, when especially mixing under oxygen exists, oxygen had affected structure or the Cu of Copper-ammonia Complex
2+With Cu
+Between balance, cause catalytic activity to increase.
Embodiment 22, synthetic iodobenzene
Undertaken by the described step of embodiment 1, but use CuO/NH
3As catalyzer, in 24 hours afterreaction systems, the productive rate of iodobenzene is 66%.
Embodiment 1,19,22 shows that method of the present invention can use monovalence copper or cupric as catalyzer, can obtain required product, but monovalence copper (cuprous) is more preferred.The contriver infers (but the present invention is not subject to concrete theoretical explanation): when using the cuprous catalysis agent, due to the impact of oxygen, have simultaneously monovalence copper and cupric in reaction system, this has increased catalytic activity.
Embodiment 23, synthetic bromobenzene
Undertaken by the described step of embodiment 1, but use KBr to replace KI as the bromine source, after 24 hours, the productive rate of bromobenzene is 62%.
Embodiment 24, synthetic chlorobenzene
Undertaken by the described step of embodiment 1, but use KCl to replace KI as the chlorine source, after 24 hours, the productive rate of chlorobenzene is 58%.
Above embodiment 23-24 shows that method of the present invention is equally applicable to other haloarene compounds such as chlorinated aromatic hydrocarbons, aryl bromide.
Embodiment 25, synthetic iodobenzene
Undertaken by the described step of embodiment 1, after dichloromethane extraction, add the 121.8mg phenylo boric acid in mother liquor, 166mgKI and 99mgK
2CO
3, react that after 24 hours, the iodobenzene productive rate is 76%.
Embodiment 26, synthetic iodobenzene
Undertaken by the described step of embodiment 1, after dichloromethane extraction, add the 121.8mg phenylo boric acid in mother liquor, 166mg KI reacts that after 24 hours, the iodobenzene productive rate is 48%.
Embodiment 27, synthetic iodobenzene
Undertaken by the described step of embodiment 25, after dichloromethane extraction, continue to add the 121.8mg phenylo boric acid in mother liquor, 166mgKI and 99mgK
2CO
3, react that after 24 hours, the iodobenzene productive rate is 74%.
Above embodiment 25-27 shows that catalyst system of the present invention does not need just can recycle through purifying treatment after reaction.
Comparative Examples 1,
Undertaken by the described step of embodiment 1, but do not add part NH
3-H
2O does not detect iodobenzene in 24 hours afterreaction systems.
Comparative Examples 2,
Undertaken by the described step of embodiment 1, but DMF only detected the iodobenzene of trace in 24 hours as solvent in the afterreaction system.
Comparative Examples 3,
Undertaken by the described step of embodiment 1, but add methyl alcohol as solvent, after 24 hours, the productive rate of iodobenzene is 72%, but by product is more.
Comparative Examples 4,
Undertaken by the described step of embodiment 1, but add acetonitrile as solvent, after 24 hours, the productive rate of iodobenzene is 64%, but by product is more.
Comparative Examples 5,
Undertaken by the described step of embodiment 1, use the nitrogen atmosphere protection, only have the iodobenzene of trace to generate after 24 hours.
For the purpose of clearer, with top each embodiment and Comparative Examples short summary as a result in following table 1,2.
Table 1, embodiment result
(a: in reaction directly with Cu
2O and NH
3-H
2O adds in reaction system, does not pass through pre-treatment.)
Table 2, Comparative Examples result
(b: in nitrogen protection, under isolated air conditions.)
From embodiment 1-27 as can be known: the aryl boric acid compound of method of the present invention from being easy to get, with the most cheap water as solvent, adopt cheap copper compound as catalyzer, under the reaction conditions of gentleness, generated haloarene compounds with high yield, and the various types of functional groups on aromatic ring are all had high tolerance, and catalyst system not needing after reaction just can recycle through purifying treatment, is a kind of universal synthesis method of novel green.
The above has described the preferred embodiment of the present invention.On the basis of reading specification sheets of the present invention, will be obvious to those skilled in the art to changing, change in these preferred implementations and replacing.The present invention can be implemented with the mode outside the specifically described mode of this paper.Therefore, all these type of equivalent embodiments have been contained in the present invention.For example, those of ordinary skills can expect that method of the present invention can be applicable to heteroaromatic compounds (as the 4-iodine pyridine) or other halogenated aromatic compound (as 2-iodoethylene base benzene) that halogen replaces equally.
Claims (4)
1. the method for a synthesizing halogen aromatic hydroxy compound, under the condition that oxygen, copper catalyst and ammoniacal liquor exist, make aryl boric acid compound and halogen MX carry out substitution reaction in water and form corresponding haloarene compounds, wherein the M in MX represents basic metal, and X represents Cl, Br or I;
The general structure of described haloarene compounds is as follows:
Formula (I)
Wherein, X represents Cl, Br or I, and R represents to be connected to 0,1 or 2 substituting group on phenyl ring, and each R represents to be selected from C independently of one another
1-C
6Alkyl, halogen atom ,-NO
2,-NHR ' ,-C (=O) OR ' ,-OR ' ,-C (=O) R ' or HOR "-substituting group; Described R ' is H or C
1-C
6Alkyl, R " be C
1-C
6Alkylidene group;
Perhaps in the situation that contain 2 substituent R, phenyl ring and two substituent R formation naphthyls, anthryl, benzimidazolyl-, benzo pyridyl, benzopyrrole base, dibenzofuran group or benzo tetrahydrofuran bases;
The general structure of described aryl boric acid compound is as follows:
Formula (II)
The definition cotype (I) of the substituent R in formula (II);
Described copper catalyst is selected from following at least a: Red copper oxide, cuprous iodide, cuprous bromide, cuprous chloride, organocopper compound and cupric oxide.
2. the method for claim 1, it is characterized in that: described method comprises two independently steps:
1) under oxygen exists, described copper catalyst and ammoniacal liquor are mixed, get catalyst system;
2) with step 1) catalyst system of gained joins in the water that contains aryl boric acid compound and halogen MX, carries out substitution reaction.
3. method as claimed in claim 1 or 2, it is characterized in that: the M in described MX represents to be selected from the basic metal of Li, Na, K, Rb or Cs.
4. method as claimed in claim 1 or 2, it is characterized in that: described reaction is carried out in air at normal temperatures and pressures.
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