CN101200429B - 2-nitro-4,5-dihalogenated phenol and 2-amino-4,5-dihalogenated phenol as well as its salt and method for synthesizing the same - Google Patents
2-nitro-4,5-dihalogenated phenol and 2-amino-4,5-dihalogenated phenol as well as its salt and method for synthesizing the same Download PDFInfo
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- CN101200429B CN101200429B CN2006101195375A CN200610119537A CN101200429B CN 101200429 B CN101200429 B CN 101200429B CN 2006101195375 A CN2006101195375 A CN 2006101195375A CN 200610119537 A CN200610119537 A CN 200610119537A CN 101200429 B CN101200429 B CN 101200429B
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- 238000000034 method Methods 0.000 title claims description 72
- 150000003839 salts Chemical class 0.000 title abstract description 12
- 150000002989 phenols Chemical class 0.000 title description 5
- 230000002194 synthesizing effect Effects 0.000 title 1
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 45
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 39
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 38
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 15
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 47
- 229910017604 nitric acid Inorganic materials 0.000 claims description 46
- -1 phenols compounds Chemical class 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 239000012467 final product Substances 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 3
- 229940117389 dichlorobenzene Drugs 0.000 claims description 3
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 27
- 238000010189 synthetic method Methods 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 235000011149 sulphuric acid Nutrition 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 32
- 238000002360 preparation method Methods 0.000 description 31
- 238000012797 qualification Methods 0.000 description 30
- 238000004811 liquid chromatography Methods 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 230000008034 disappearance Effects 0.000 description 24
- 230000002829 reductive effect Effects 0.000 description 22
- 239000007787 solid Substances 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 18
- NTMLWWAGIHZWQT-UHFFFAOYSA-N 5-fluoro-4-iodo-2-nitrophenol Chemical class Oc1cc(F)c(I)cc1[N+]([O-])=O NTMLWWAGIHZWQT-UHFFFAOYSA-N 0.000 description 15
- CSQWLXZVUXRZFL-UHFFFAOYSA-N 3-fluoro-4-iodophenol Chemical compound OC1=CC=C(I)C(F)=C1 CSQWLXZVUXRZFL-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- MGQHWQPZDBGSTR-UHFFFAOYSA-N 2-amino-4-bromo-5-fluorophenol Chemical class NC1=CC(Br)=C(F)C=C1O MGQHWQPZDBGSTR-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 238000004821 distillation Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 7
- 230000006837 decompression Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMSFGDZCAYKXOE-UHFFFAOYSA-N 4-bromo-5-fluoro-2-nitrophenol Chemical class OC1=CC(F)=C(Br)C=C1[N+]([O-])=O ZMSFGDZCAYKXOE-UHFFFAOYSA-N 0.000 description 5
- RYSFWISANLBRRZ-UHFFFAOYSA-N 5-bromo-4-fluoro-2-nitrophenol Chemical class OC1=CC(Br)=C(F)C=C1[N+]([O-])=O RYSFWISANLBRRZ-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000004904 shortening Methods 0.000 description 5
- QWTULQLVGNZMLF-UHFFFAOYSA-N 3-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C(Br)=C1 QWTULQLVGNZMLF-UHFFFAOYSA-N 0.000 description 4
- MRQYTJXVULSNIS-UHFFFAOYSA-N 4-bromo-3-fluorophenol Chemical compound OC1=CC=C(Br)C(F)=C1 MRQYTJXVULSNIS-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- PFIFEHHRRXFNFI-UHFFFAOYSA-N 2-amino-4-fluoro-5-iodophenol Chemical compound Nc1cc(F)c(I)cc1O PFIFEHHRRXFNFI-UHFFFAOYSA-N 0.000 description 3
- GHYOKMYZWDAXJW-UHFFFAOYSA-N 3-bromo-4-iodophenol Chemical compound OC1=CC=C(I)C(Br)=C1 GHYOKMYZWDAXJW-UHFFFAOYSA-N 0.000 description 3
- DIBGHLUZOSSRIT-UHFFFAOYSA-N 3-chloro-4-iodophenol Chemical compound OC1=CC=C(I)C(Cl)=C1 DIBGHLUZOSSRIT-UHFFFAOYSA-N 0.000 description 3
- AQERVRQXHVITFA-UHFFFAOYSA-N 4-bromo-3-iodophenol Chemical compound OC1=CC=C(Br)C(I)=C1 AQERVRQXHVITFA-UHFFFAOYSA-N 0.000 description 3
- NIJGUZDHXGCACM-UHFFFAOYSA-N 4-bromo-5-iodo-2-nitrophenol Chemical class Oc1cc(I)c(Br)cc1[N+]([O-])=O NIJGUZDHXGCACM-UHFFFAOYSA-N 0.000 description 3
- QMDMLMOPLZBFTC-UHFFFAOYSA-N 4-fluoro-3-iodophenol Chemical compound OC1=CC=C(F)C(I)=C1 QMDMLMOPLZBFTC-UHFFFAOYSA-N 0.000 description 3
- BOYSKVGATQWYEU-UHFFFAOYSA-N 4-fluoro-5-iodo-2-nitrophenol Chemical compound Oc1cc(I)c(F)cc1[N+]([O-])=O BOYSKVGATQWYEU-UHFFFAOYSA-N 0.000 description 3
- OYUQIHFWANFUCN-UHFFFAOYSA-N 5-bromo-4-iodo-2-nitrophenol Chemical class Oc1cc(Br)c(I)cc1[N+]([O-])=O OYUQIHFWANFUCN-UHFFFAOYSA-N 0.000 description 3
- KDJOCTVZGZYTGJ-UHFFFAOYSA-N 5-chloro-4-iodo-2-nitrophenol Chemical class Oc1cc(Cl)c(I)cc1[N+]([O-])=O KDJOCTVZGZYTGJ-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- FLJGRKJRMHAKMV-UHFFFAOYSA-N 2-amino-4,5-dibromophenol Chemical class NC1=CC(Br)=C(Br)C=C1O FLJGRKJRMHAKMV-UHFFFAOYSA-N 0.000 description 2
- VBNHKNJEBKFCLP-UHFFFAOYSA-N 2-amino-4-bromo-5-iodophenol Chemical class Nc1cc(Br)c(I)cc1O VBNHKNJEBKFCLP-UHFFFAOYSA-N 0.000 description 2
- GCYOGURFDSTWMI-UHFFFAOYSA-N 2-amino-4-chloro-5-iodophenol Chemical class NC1=CC(Cl)=C(I)C=C1O GCYOGURFDSTWMI-UHFFFAOYSA-N 0.000 description 2
- QRRYTSCZSPPVQQ-UHFFFAOYSA-N 2-amino-5-bromo-4-fluorophenol Chemical compound NC1=CC(F)=C(Br)C=C1O QRRYTSCZSPPVQQ-UHFFFAOYSA-N 0.000 description 2
- CCFOPSWHHZPDRR-UHFFFAOYSA-N 2-amino-5-bromo-4-iodophenol Chemical class Nc1cc(I)c(Br)cc1O CCFOPSWHHZPDRR-UHFFFAOYSA-N 0.000 description 2
- SHJLQMPWDJBRDG-UHFFFAOYSA-N 2-amino-5-chloro-4-iodophenol Chemical class NC1=CC(I)=C(Cl)C=C1O SHJLQMPWDJBRDG-UHFFFAOYSA-N 0.000 description 2
- YODVHBXBACNADC-UHFFFAOYSA-N 2-amino-5-fluoro-4-iodophenol Chemical class NC1=CC(I)=C(F)C=C1O YODVHBXBACNADC-UHFFFAOYSA-N 0.000 description 2
- FDHXSXGNKTYRRU-UHFFFAOYSA-N 4-bromo-5-chloro-2-nitrophenol Chemical compound OC1=CC(Cl)=C(Br)C=C1[N+]([O-])=O FDHXSXGNKTYRRU-UHFFFAOYSA-N 0.000 description 2
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 2
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 2
- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- SJQSLNQDGSGNIY-UHFFFAOYSA-N Nc1cc(I)c(I)cc1O Chemical class Nc1cc(I)c(I)cc1O SJQSLNQDGSGNIY-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- 0 *c(c(*)c1)cc(*)c1O Chemical compound *c(c(*)c1)cc(*)c1O 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- FXDRSNMVNIIREK-UHFFFAOYSA-N 2-amino-4-bromo-5-chlorophenol Chemical class Nc1cc(Br)c(Cl)cc1O FXDRSNMVNIIREK-UHFFFAOYSA-N 0.000 description 1
- UZBQKENIGKFOOH-UHFFFAOYSA-N 2-amino-5-bromo-4-fluorophenol hydrochloride Chemical compound C1=C(C(=CC(=C1F)Br)O)N.Cl UZBQKENIGKFOOH-UHFFFAOYSA-N 0.000 description 1
- XYDBYPGONFBVFE-UHFFFAOYSA-N 4,5-dibromo-2-nitrophenol Chemical compound [N+](=O)([O-])C1=C(C=C(C(=C1)Br)Br)O XYDBYPGONFBVFE-UHFFFAOYSA-N 0.000 description 1
- PYEFRXVTJOHQDM-UHFFFAOYSA-N 4-chloro-5-iodo-2-nitrophenol Chemical compound C1=C(C(=CC(=C1Cl)I)O)[N+](=O)[O-] PYEFRXVTJOHQDM-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- UTNSUDAYROCVPS-UHFFFAOYSA-N Oc1cc(I)c(I)cc1[N+]([O-])=O Chemical compound Oc1cc(I)c(I)cc1[N+]([O-])=O UTNSUDAYROCVPS-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- JGJLWPGRMCADHB-UHFFFAOYSA-N hypobromite Inorganic materials Br[O-] JGJLWPGRMCADHB-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Abstract
The invention discloses novel 2-nitro-4, 5-phenyldihalide compound and 2-amido-4, 5- phenyldihalide compound shown in formula I, wherein, A is NO2 or NH2; when A is NO2, R is zero; X is F, Y is I or Br; or X is Cl, Y is I; or X is Br, Y is F or I; or X is I, Y is F or Br; when A is NH2, R is zero, HCl, H2SO4 or CH3COOH; X is F, Y is Br or I; or X is Cl, Y is Br or I; or X is Br, Y is F, Br or I; or X is I, Y is Cl, Br, F or I. The invention also discloses a synthetic method. The synthetic method can high selectively obtain 2-nitro-4, 5-phenyldihalide compound and 2-amido-4, 5- phenyldihalide compound and as well as the salt of the products; the raw materials are cheap, and the operation is simple; the invention can be applied to scale production easily and the prospect of industrial application is very bright.
Description
Technical field
The present invention relates to novel 2-nitro-4,5-bihalogenated phenols compounds and 2-amino-4,5-bihalogenated phenols compounds and salt thereof, and compound method.
Background technology
Existing document discloses part 2-nitro-4, and the 5-bihalogenated phenols compounds is used for organic synthesis, agricultural chemicals, medicine and other fields.Some important chemical products and the molecule with physiologically active have all comprised the structural unit of this compounds.Like patent documentation WO 2006105262 a kind of compound that relates to the disease that is caused by the DNA infringement in the dna replication dna process is disclosed, shown in formula III.Patent documentation WO 0066569 discloses a kind of active ingredient of weedicide for another example, shown in IV and formula V.
Formula III formula IV
Formula V
Summary of the invention
The 2-nitro-4 that the objective of the invention is open novelty, 5-bihalogenated phenols compounds and 2-amino-4,5-bihalogenated phenols compounds and salt thereof.
Compound of the present invention is suc as formula shown in the I:
Wherein, A is NO
2Or NH
2
When A is NO
2The time, R is not for having; X is F, and Y is I or Br; Or X is Cl, and Y is I; Or X is Br, and Y is F or I; Or X is I, and Y is F or Br; Wherein preferred X is F, and Y is Br;
When A is NH
2The time, R is nothing, HCl, H
2SO
4Or CH
3COOH; X is F, and Y is Br or I; Or X is Cl, and Y is Br or I; Or X is Br, and Y is F, Br or I; Or X is I, and Y is Cl, Br, F or I.
Another object of the present invention provides 2-nitro-4 of the present invention; The compound method of 5-bihalogenated phenols compounds the steps include: that 4-bihalogenated phenols compounds and concentration are more than or equal to the nitric acid of weight percent 65% with 3 shown in the formula II; With mol ratio 1: 0.5～1: 1.5 in solvent; Under 0～100 ℃ of temperature of reaction, react, the reaction times is 1～10 hour, gets final product;
Wherein, X is F, and Y is I or Br; Or X is Cl, and Y is I; Or X is Br, and Y is F or I; Or X is I, and Y is F or Br.
Wherein, described suc as formula 3 shown in the II, the 4-bihalogenated phenols compounds, wherein X is F, Y is I or Br; Or X is Br, and Y is F, commercially available getting.
Wherein, described suc as formula 3 shown in the II, the 4-bihalogenated phenols compounds, wherein X is Cl, Y is I; Or X is Br, and Y is I; Or X is I, and Y is F or Br, can be according to making suc as formula the reaction shown in the VI:
Formula VI
What wherein, described nitric acid was preferable is the nitrosonitric acid of concentration more than or equal to weight percent 90%; Described 3, what the mol ratio of 4-bihalogenated phenols compounds and nitric acid was preferable is 1: 0.7～1: 1.2, and better is 1: 0.7～1: 0.99; What described temperature of reaction was preferable is 0～50 ℃, and better is 0～30 ℃.
Wherein, described preferred solvents be methylene dichloride, chloroform, tetracol phenixin, 1,2-ethylene dichloride, vinyl trichloride, sym.-tetrachloroethane, chlorobenzene, dichlorobenzene, oil of mirbane, acetonitrile, Nitromethane 99Min., benzyl cyanide, sulfuric acid or acetic acid.
Wherein, when solvent was sulfuric acid or acetic acid, what described temperature of reaction was preferable was 0～35 ℃.
It is amino-4 that another purpose of the present invention provides 2-of the present invention, and the compound method of 5-bihalogenated phenols compounds the steps include: suc as formula the 2-nitro-4 shown in the I, the 5-bihalogenated phenols compounds, and wherein A is NO
2R is not for having; X is F, and Y is Br or I; Or X is Cl, and Y is Br or I; Or X is Br, and Y is F, Br or I; Or X is I, and Y is Cl, Br, F or I; With reductive agent in solvent, under temperature of reaction-10～50 ℃, react, get final product.
Wherein, described suc as formula the 2-nitro-4 shown in the I, the 5-bihalogenated phenols compounds, wherein A is NO
2The time, R is not for having; X is F, and Y is I or Br; Or X is Cl, and Y is I; Or X is Br, and Y is F or I; Or X is I, and Y is F or Br, can be made by compound method of the present invention.
Wherein, described suc as formula the 2-nitro-4 shown in the I, the 5-bihalogenated phenols compounds, wherein A is NO
2R is not for having; Or X is Cl, and Y is Br; Or X is Br, and Y is Br; Or X is I, and Y is Cl or I, all commercially available getting.
Wherein, what the molar weight of described reductive agent was preferable is the 2-nitro-4 described in the inventive method, 2.0～3.5 times of 5-bihalogenated phenols compounds molar weight; That described reductive agent is preferable is iron, tin, zinc, tindichloride, iron protochloride, LiAlH
4Or hydrogen; Described temperature of reaction is preferable is-10-30 ℃; Described preferred solvents be methyl alcohol, ethanol, propyl alcohol, Virahol, THF, 1,4-dioxane, ethers or alcohols; Described ethers such as methyl-phenoxide, described alcohols such as butanols.
Wherein, when reductive agent is hydrogen, in reactant, also add catalyst P d, Raney Ni, Rh or Ru etc. react preferable under the pressure of 50～200psi, carrying out.
Further purpose of the present invention provides 2-of the present invention amino-4; The compound method of the salt of 5-bihalogenated phenols compounds; It is characterized in that: with 2-amino-4 of the present invention, 5-bihalogenated phenols compounds and hydrochloric acid, hydrogen chloride gas, sulfuric acid or acetic acid react, and get final product.
Wherein, behind acid-respons, can fully stir, leave standstill filtration, get final product to such an extent that 2-is amino-4, the solid of the salt of 5-phenyl-dihalide phenolic compound.
Positive progressive effect of the present invention is: it is novel in the 2-nitro-4 shown in the I to the invention discloses, 5-bihalogenated phenols compounds and 2-amino-4,5-bihalogenated phenols compounds and salt thereof, and compound method.But compound method highly selective of the present invention obtain 2-nitro-4,5-bihalogenated phenols compounds and 2-are amino-4,5-bihalogenated phenols compounds and salt thereof, and raw material is cheap are simple to operate, are easy to large-scale production, have higher prospects for commercial application.
Embodiment
Mode through embodiment further specifies the present invention below, does not therefore limit the present invention among the described scope of embodiments.
Embodiment 1～7 2-nitro-4, the 5-bihalogenated phenols compounds
Table 1 has provided structure suc as formula the 2-nitro-4 shown in the I, 5-bihalogenated phenols compounds embodiment 1～7.
Table 1 2-nitro-4,5-bihalogenated phenols compounds embodiment 1～7
| Embodiment | A | X | Y | R | Embodiment | A | X | Y | R |
| 1 | NO 2 | F | I | \ | 5 | NO 2 | Br | I | \ |
| 2 | NO 2 | F | Br | \ | 6 | NO 2 | I | F | \ |
| 3 | NO 2 | Cl | I | \ | 7 | NO 2 | I | Br | \ |
| 4 | NO 2 | Br | F | \ |
Embodiment 8～29 2-amino-4,5-bihalogenated phenols compounds and salt thereof
Table 2 has provided structure suc as formula the amino of the 2-shown in the I-4,5-bihalogenated phenols compounds and salt embodiment 8～29 thereof.
Table 2 2-amino-4,5-bihalogenated phenols compounds and salt embodiment 8～29 thereof
| Embodiment | A | X | Y | R | Embodiment | A | X | Y | R |
| 8 | NH 2 | F | Br | \ | 19 | NH 2 | F | Br | HCl |
| 9 | NH 2 | F | I | \ | 20 | NH 2 | F | I | H 2SO 4 |
| 10 | NH 2 | Cl | Br | \ | 21 | NH 2 | Cl | Br | CH 3COOH |
| 11 | NH 2 | Cl | I | \ | 22 | NH 2 | Cl | I | HCl |
| 12 | NH 2 | Br | Br | \ | 23 | NH 2 | Br | Br | H 2SO 4 |
| 13 | NH 2 | Br | F | \ | 24 | NH 2 | Br | F | CH 3COOH |
| 14 | NH 2 | Br | I | \ | 25 | NH 2 | Br | I | HCl |
| 15 | NH 2 | I | F | \ | 26 | NH 2 | I | F | H 2SO 4 |
| 16 | NH 2 | I | Br | \ | 27 | NH 2 | I | Br | CH 3COOH |
| 17 | NH 2 | I | Cl | \ | 28 | NH 2 | I | Cl | HCl |
| 18 | NH 2 | I | I | \ | 29 | NH 2 | I | I | H 2SO 4 |
Method embodiment 1 preparation 2-nitro-4-fluoro-5-iodophenol
4-fluorophenol (0.2mol), triethylamine (0.24mol) joins methylene dichloride (300mL), and the back room temperature that stirs drips aceticanhydride (0.20mol).Reflux to raw material 4-fluorophenol disappearance (HPLC tracking) then.Reacting liquid filtering, filtrate decompression concentrate and obtain acetic acid 4-fluorobenzene phenolic ester.
Above-mentioned resulting acetic acid 4-fluorobenzene phenolic ester (0.1mol) is joined methylene dichloride (250mL) solution, and stirring at room adds iodine (0.12mol) after following 0.5 hour.Reflux is stirred to raw material acetic acid 4-fluorobenzene phenolic ester disappearance (HPLC tracking) then.The aqueous sodium hydroxide solution of adding 25% behind the reaction solution concentrating under reduced pressure; And be heated to 90 ℃ of stirrings after 3 hours; Add concentrated hydrochloric acid behind the cool to room temperature and regulate pH=2-3, leave standstill, filter, drying obtains 3-iodo-4-fluorophenol, it is 60% that chlorination goes on foot overall yield with hydrolysis two.
3-iodo-4-fluorophenol (0.314mol) is dissolved in 1,2-ethylene dichloride (200mL).At room temperature, drip the nitric acid (0.157mol) of weight ratio 75%; The mol ratio of nitric acid is 1: 0.5 in 3-iodo-4-fluorophenol and the aqueous nitric acid.The back reaction under 50-55 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 2 hours and is disappeared.Reaction solution concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-fluoro-5-iodophenol, and productive rate is 74%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝7.35(1H，d，J＝8.0Hz)，7.50(1H，d，J＝12.1Hz)，9.75(1H，broad)。
Method embodiment 2 preparation 2-nitro-4-fluoro-5-bromophenols
3-bromo-4-fluorophenol (0.314mol) is dissolved in the acetic acid (200mL).At room temperature, the dropping weight ratio is 90% nitric acid (0.377mol); The mol ratio of nitric acid is 1: 1.2 in 3-bromo-4-fluorophenol and the aqueous nitric acid.Mix even back and react 8 hours down to the disappearance of performance liquid chromatography (HPLC) tracking raw material in 0-5 ℃.Cooling adds 30% sodium hydroxide solution neutralization reaction liquid down to neutral, and (3 * 150mL) extract methylene dichloride, and the organic layer after the merging is used anhydrous magnesium sulfate drying, filter.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-fluoro-5-bromophenol, and productive rate is 86%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝7.65(1H，d，J＝11.5Hz)，7.74(1H，d，J＝8.4Hz)，9.86(1H，broad)。
Method embodiment 3 preparation 2-nitro-4-fluoro-5-bromophenols
3-bromo-4-fluorophenol (0.314mol) is dissolved in the sulfuric acid (200mL).At room temperature, drip the nitric acid (0.251mol) of weight percent 95%; The mol ratio of nitric acid is 1: 0.8 in 3-bromo-4-fluorophenol and the aqueous nitric acid.Mix even back and react 7 hours down to the disappearance of performance liquid chromatography (HPLC) tracking raw material in 30-35 ℃.Cooling adds 30% sodium hydroxide solution neutralization reaction liquid down to neutral, and (3 * 150mL) extract methylene dichloride, and the organic layer after the merging is used anhydrous magnesium sulfate drying, filter.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-fluoro-5-bromophenol, and productive rate is 75%, and qualification result is with method embodiment 3.
Method embodiment 4 preparation 2-nitro-4-iodo-5-chlorophenols
4-iodophenol (0.2mol), triethylamine (0.24mol) joins methylene dichloride (300mL), and the back room temperature that stirs drips aceticanhydride (0.20mol).Reflux to raw material 4-iodophenol disappearance (HPLC tracking) then.Reacting liquid filtering, filtrate decompression concentrate and obtain acetic acid 4-iodobenzene phenolic ester.
Acetic acid 4-iodobenzene phenolic ester (0.1mol) is joined in the methylene dichloride (250mL), feed chlorine (0.12mol) under the room temperature.Slowly temperature rising reflux is up to acetic acid 4-iodobenzene phenolic ester disappearance (HPLC tracking).The reaction solution concentrating under reduced pressure adds 25% aqueous sodium hydroxide solution, and is heated to 90 ℃ and stirs 1 hour postcooling after room temperature, regulates pH=2-3 with concentrated hydrochloric acid, leaves standstill, filters, drying obtains 3-chloro-4-iodophenol, and it is 75% that chlorination goes on foot overall yield with hydrolysis two.
3-chloro-4-iodophenol (0.314mol) is dissolved in the dichlorobenzene (200mL).At room temperature, the nitric acid of weight ratio 80% (0.283mol); The mol ratio of nitric acid is 1: 0.90 in 3-chloro-4-iodophenol and the aqueous nitric acid.Mix even back and react 6 hours down to the disappearance of performance liquid chromatography (HPLC) tracking raw material in 30-35 ℃.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-chlorophenol, and productive rate is 89%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝6.70(1H，s)，8.33(1H，s)，9.84(1H，broad)。
Method embodiment 5 preparation 2-nitro-4-bromo-5-fluorophenols
3-fluoro-4-bromophenol (0.314mol) is dissolved in the methylene dichloride (200mL).At room temperature, the adding weight percent is 95% nitric acid (0.310mol); The mol ratio of nitric acid is 1: 0.99 in 3-fluoro-4-bromophenol and the aqueous nitric acid.After mixing thoroughly, under 20-25 ℃, react and followed the tracks of raw material to performance liquid chromatography (HPLC) in 4 hours and disappear and promptly get, concentrating under reduced pressure, drying obtains yellow solid 2-nitro-4-bromo-5-fluorophenol, and productive rate is 82%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝6.65(1H，d，J＝12.0Hz)，8.06(1H，d，J＝8.4Hz)，9.76(1H，broad)。
Method embodiment 6 preparation 2-nitro-4-bromo-5-iodophenols
4-bromophenol (0.2mol), triethylamine (0.24mol) joins methylene dichloride (300mL), and the back room temperature that stirs drips aceticanhydride (0.20mol).Reflux to raw material 4-bromophenol disappearance (HPLC tracking) then.Reacting liquid filtering, filtrate decompression concentrate and obtain acetic acid 4-bromobenzene phenolic ester.
With acetic acid 4-bromobenzene phenolic ester (0.1mol) dissolving methylene dichloride (250mL) solution, stirring at room added iodine (0.12mol) in following 0.5 hour.Slowly reflux to raw material acetic acid 4-bromobenzene phenolic ester disappearance (HPLC tracking).The reaction solution concentrating under reduced pressure; Add 25% aqueous sodium hydroxide solution then, and be heated to 90 ℃ and stir 1 hour postcooling, reaction solution adds concentrated hydrochloric acid and regulates pH=2-3; Leave standstill, filtration, filtration drying obtain 3-iodo-4-bromophenol, chlorination and two step of hydrolysis overall yield are 66%.
3-iodo-4-bromophenol (0.314mol) is dissolved in the trichloromethane (200mL).At room temperature, drip the nitric acid (0.22mol) of weight percent 65%; The mol ratio of nitric acid is 1: 0.7 in 3-iodo-4-bromophenol and the aqueous nitric acid.Mix even back and react 10 hours down to the disappearance of performance liquid chromatography (HPLC) tracking raw material in 25-30 ℃.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-bromo-5-iodophenol, and productive rate is 62%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝7.40(1H，s)，7.94(1H，s)，9.68(1H，broad)。
Method embodiment 7 preparation 2-nitro-4-iodo-5-bromophenols
The acetic acid 4-iodobenzene phenolic ester (0.1mol) that method embodiment 4 is made joins in methylene dichloride (150mL) solution.Add bromine water (0.10mol) under the stirring at room.Slowly reflux is stirred to raw material acetic acid 4-iodobenzene phenolic ester disappearance (HPLC tracking).The reaction solution concentrating under reduced pressure; Be cooled to and add 25% aqueous sodium hydroxide solution after the room temperature, and be heated to 90 ℃ of stirring heating 2 hours, add concentrated hydrochloric acid behind the cool to room temperature and regulate pH=2-3; Leave standstill, filter, filter drying and obtain 3-bromo-4-iodophenol, bromination and two step of hydrolysis overall yield are 82%.
3-bromo-4-iodophenol (0.314mol) is dissolved in the tetracol phenixin (200mL).At room temperature add weight ratio and be 95% nitric acid (0.408mol); The mol ratio of nitric acid is 1: 1.2 in 3-bromo-4-iodophenol and the aqueous nitric acid.Under 45-50 ℃, react and followed the tracks of raw material to performance liquid chromatography (HPLC) in 2 hours and disappear and promptly get, concentrating under reduced pressure, drying obtains yellow solid 2-nitro-4-iodo-5-bromophenol, and productive rate is 56%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝6.98(1H，s)，8.22(1H，s)，9.76(1H，broad)。
Method embodiment 8 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in benzyl cyanide (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝6.40(1H，d，J＝11.2Hz)，8.30(1H，d，J＝8.0Hz)，9.80(1H，broad)。
Method embodiment 9 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in sym.-tetrachloroethane (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 10 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in Nitromethane 99Min. (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 11 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in oil of mirbane (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 12 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in chlorobenzene (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 13 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in acetonitrile (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 14 preparation 2-nitro-4-iodo-5-fluorophenols
3-fluoro-4-iodophenol (0.314mol) is dissolved in vinyl trichloride (150mL).At room temperature, drip the nitric acid (0.471mol) of weight ratio 85%; The mol ratio of nitric acid is 1: 1.5 in 3-fluoro-4-iodophenol and the aqueous nitric acid.The back reaction under 90-100 ℃ that stirs was followed the tracks of raw material to performance liquid chromatography (HPLC) in 1 hour and is disappeared.Concentrating under reduced pressure, drying obtain yellow solid 2-nitro-4-iodo-5-fluorophenol, and productive rate is 45%, and qualification result is with method embodiment 8.
Method embodiment 15 preparation 2-amino-4-bromo-5-fluorophenols
2-nitro-4-bromo-5-fluorophenol (0.1mol) that method embodiment 5 is prepared is dissolved in methyl alcohol (100mL).(21g, 0.2mol), react under 25-30 ℃ to the disappearance of performance liquid chromatography (HPLC) tracking raw material the back that stirs at room temperature to add tindichloride (0.20mol) and hydrochloric acid.Reaction solution uses the sodium hydroxide pH value that neutralizes to be neutrality, filter, filtrating with ETHYLE ACETATE (3 * 200mL) extractions, the organic layer after the merging obtains 2-amino-4-bromo-5-fluorophenol with anhydrous magnesium sulfate drying, underpressure distillation, productive rate is 87%, qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.04(1H，d，J＝9.2Hz)，7.50(1H，d，J＝7.2Hz)，11.65(1H，broad)。
Method embodiment 16 preparation 2-amino-4-bromo-5-fluorophenols
2-nitro-4-bromo-5-fluorophenol (0.1mol) that method embodiment 5 is prepared is dissolved in the ethanol (100mL), adds 5%Pd/C (0.2g) at room temperature, carries out shortening, and pressure is 50-55psi.Be stirred to performance liquid chromatography (HPLC) under 20-25 ℃ and follow the tracks of the raw material disappearance.Reacting liquid filtering, filtrate decompression concentrate, drying obtains light yellow solid 2-amino-4-bromo-5-fluorophenol, and productive rate is 91%, and qualification result is with method embodiment 15.
Method embodiment 17 preparation 2-amino-4-bromo-5-fluorophenols
2-nitro-4-bromo-5-fluorophenol (0.1mol) that method embodiment 5 is prepared is dissolved in THF (100mL).At room temperature add LiAlH
4(0.30mol) under 40-45 ℃, react to the disappearance of performance liquid chromatography (HPLC) tracking raw material.The reaction solution cooling drips methyl alcohol down, and (3 * 100mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain 2-amino-4-bromo-5-fluorophenol, and productive rate is 82%, and qualification result is with method embodiment 15 with ETHYLE ACETATE fully to stir the back.
The hydrochloride of method embodiment 18 preparation 2-amino-4-bromo-5-fluorophenols
2-amino-4-bromo-5-fluorophenol (0.03moL) that method embodiment 17 is made is dissolved in ETHYLE ACETATE (70mL); Feed hydrogen chloride gas under the room temperature; After 2 hours, reaction solution leaves standstill, filters, drying obtains 2-amino-hydrochloride of 4-bromo-5-fluorophenol, and qualification result is with method embodiment 15.
The acetate of method embodiment 19 preparation 2-amino-4-bromo-5-fluorophenols
The 2-amino that method embodiment 17 makes-4-bromo-5-fluorophenol (0.03moL) is dissolved in the ether (50mL); Stir under the room temperature and add acetic acid (0.05moL) down; Stir leave standstill after 0.5 hour, filter, drying obtains 2-amino-acetate of 4-bromo-5-fluorophenol, qualification result is with method embodiment 15.
Method embodiment 20 preparation 2-amino-4-bromo-5-chlorophenols
2-nitro-4-bromo-5-chlorophenol (0.1moL) is dissolved in methyl alcohol (100mL), and (21g 0.2mol), fully stirs the back and under 20-25 ℃, reacts to the disappearance of performance liquid chromatography (HPLC) tracking raw material at room temperature to add glass putty (0.35mol) and concentrated hydrochloric acid.Reaction solution adds sodium hydroxide and regulates the pH value to neutrality under cooling, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain 2-amino-4-bromo-5-chlorophenate hydrochlorate, and yield is 77%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.06(1H，s)，7.52(1H，s)，11.68(1H，broad)。
Method embodiment 21 preparation 2-amino-4-bromo-5-chlorophenate hydrochlorates
2-nitro-4-bromo-5-chlorophenol (0.1moL) is dissolved in the methyl alcohol (100mL), adds 10%Pd/C (0.15g) at room temperature, carry out shortening, pressure is 100psi.Be stirred to performance liquid chromatography (HPLC) under 30-35 ℃ and follow the tracks of the raw material disappearance.Material after reacting liquid filtering, filtrate decompression concentrate is dissolved in the THF (100mL); Feed hydrogen chloride gas under the room temperature; 1.5 leave standstill, filter after hour, drying obtains 2-amino-4-bromo-5-chlorophenate hydrochlorate, yield is 81%, qualification result is with method embodiment 20.
Method embodiment 22 preparation 2-amino-4-bromo-5-bromophenols
2-nitro-4-bromo-5-bromophenol (0.1mol) is dissolved in Virahol (100mL).At room temperature add zinc powder (0.3mol).Under 45-50 ℃, be stirred to performance liquid chromatography (HPLC) and follow the tracks of the raw material disappearance.Reaction solution is regulated the pH value to neutrality with saturated sodium hydroxide solution, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain light yellow solid 2-amino-4-bromo-5-bromophenol, and productive rate is 74%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.00(1H，s)，7.46(1H，s)，11.60(1H，broad)。
Method embodiment 23 preparation 2-amino-4-iodo-5-iodophenols
2-nitro-4-iodo-5-iodophenol (0.1mol) is dissolved in Virahol (100mL).At room temperature add zinc powder (0.3mol).Under 45-50 ℃, be stirred to performance liquid chromatography (HPLC) and follow the tracks of the raw material disappearance.Reaction solution is regulated the pH value to neutrality with saturated sodium hydroxide solution, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain light yellow solid 2-amino-4-iodo-5-iodophenol, and productive rate is 74%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.00(1H，s)，7.30(1H，s)，11.56(1H，broad)。
Method embodiment 24 preparation 2-amino-4-chloro-5-iodophenols
2-nitro-4-chloro-5-iodophenol (0.1mol) is dissolved in Virahol (100mL).At room temperature add iron powder (0.35mol).Under-10-0 ℃, being stirred to performance liquid chromatography (HPLC) follows the tracks of raw material and disappears.Reaction solution is regulated the pH value to neutrality with saturated sodium hydroxide solution, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain light yellow solid 2-amino-4-chloro-5-iodophenol, and productive rate is 70%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.02(1H，s)，7.44(1H，s)，11.58(1H，broad)。
Method embodiment 25 preparation 2-amino-4-fluoro-5-bromophenol and hydrochlorides thereof
2-nitro-4-fluoro-5-bromophenol (0.05moL) that method embodiment 3 is prepared is dissolved in methyl alcohol (100mL), at room temperature adds Raney Ni (0.20g), carries out shortening, and pressure is 200psi.Be stirred to performance liquid chromatography (HPLC) under 3035 ℃ and follow the tracks of the raw material disappearance.Reacting liquid filtering promptly gets 2-amino-4-fluoro-5-bromophenol solution.It is at room temperature fed hydrogen chloride gas, after 2.0 hours, leave standstill, filter, drying obtains 2-amino-4-fluoro-5-bromophenol hydrochloride, yield is 95%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.04(1H，d，J＝7.2Hz)，7.50(1H，d，J＝9.2Hz)，11.62(1H，broad)。
Method embodiment 26 preparation 2-amino-4-bromo-5-iodophenols
2-nitro-4-bromo-5-iodophenol (0.05moL) that method embodiment 6 is prepared is dissolved in the methyl alcohol (100mL), adds Rh (0.15g) at room temperature, carries out shortening, and pressure is 50-55psi.Be stirred to performance liquid chromatography (HPLC) under-10--5 ℃ and follow the tracks of the raw material disappearance.After reacting liquid filtering, filtrate decompression concentrate, promptly get 2-amino-4-bromo-5-iodophenol, qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.00(1H，s)，7.36(1H，s)，11.62(1H，broad)。
Method embodiment 27 preparation 2-amino-4-iodo-5-bromophenols
2-nitro-4-iodo-5-bromophenol (0.05moL) that method embodiment 7 is prepared is dissolved in the methyl alcohol (100mL), adds Ru (0.15g) at room temperature, carries out shortening, and pressure is 75-80psi.Be stirred to performance liquid chromatography (HPLC) under 0-5 ℃ and follow the tracks of the raw material disappearance.After reacting liquid filtering, filtrate decompression concentrate, promptly get 2-amino-4-iodo-5-bromophenol, qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.02(1H，s)，7.42(1H，s)，11.60(1H，broad)。
Method embodiment 28 preparation 2-amino-4-fluoro-5-iodophenol and vitriol thereof
Preparation 2-nitro-4-fluoro-5-iodophenol (0.05moL) that method embodiment 1 is prepared is dissolved in methyl alcohol (100mL).(21g, 0.2mol), react under 20-25 ℃ to the disappearance of performance liquid chromatography (HPLC) tracking raw material the back that stirs at room temperature to add iron protochloride (0.175mol) and hydrochloric acid.Reaction solution uses the sodium hydroxide pH value that neutralizes to be neutrality, filters, and (3 * 200mL) extractions, the organic layer after the merging promptly gets 2-amino-4-fluoro-5-iodophenol solution to filtrating with ETHYLE ACETATE.Under stirring at room, drip after sulfuric acid (0.3mol) fully stirs, leave standstill, filter, drying obtains 2-amino-4-fluoro-5-iodophenol vitriol, productive rate is 80%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.00(1H，d，J＝7.2Hz)，7.46(1H，d，J＝9.2Hz)，11.62(1H，broad)。
Method embodiment 29 preparation 2-amino-4-iodo-5-chlorophenols
2-nitro-4-iodo-5-chlorophenol (0.1mol) that method embodiment 4 is made is dissolved in Virahol (100mL).At room temperature add zinc powder (0.3mol).Under 45-50 ℃, be stirred to performance liquid chromatography (HPLC) and follow the tracks of the raw material disappearance.Reaction solution is regulated the pH value to neutrality with saturated sodium hydroxide solution, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain light yellow solid 2-amino-4-iodo-5-chlorophenol, and productive rate is 80%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.00(1H，s)，7.46(1H，s)，11.64(1H，broad)。
Method embodiment 30 preparation 2-amino-4-iodo-5-fluorophenols
With what method embodiment 8 made 2-nitro-4-iodo-5-fluorophenol (0.1mol) is dissolved in Virahol (100mL).At room temperature add zinc powder (0.3mol).Under 45-50 ℃, be stirred to performance liquid chromatography (HPLC) and follow the tracks of the raw material disappearance.Reaction solution is regulated the pH value to neutrality with saturated sodium hydroxide solution, ETHYLE ACETATE (3 * 200mL) extract, and merge organic layer, and anhydrous magnesium sulfate drying, underpressure distillation obtain light yellow solid 2-amino-4-iodo-5-fluorophenol, and productive rate is 75%, and qualification result is following:
1H?NMR(DMSO-d
6)：δ＝4.00(2H，broad)，7.04(1H，d，J＝9.2Hz)，7.50(1H，d，J＝7.2Hz)，11.62(1H，broad)。
Claims (7)
1. one kind suc as formula the 2-nitro-4 shown in the I; The compound method of 5-bihalogenated phenols compounds is characterized in that: with 3 shown in the formula II, 4-bihalogenated phenols compounds and concentration are more than or equal to the nitric acid of weight percent 65%; With mol ratio 1: 0.5～1: 1.5 in solvent; Under 0～100 ℃ of temperature of reaction, react, the reaction times is 1～10 hour, gets final product;
A is NO
2, R is not for having; X is F, and Y is I or Br; Or X is Cl, and Y is I; Or X is Br, and Y is F or I; Or X is I, and Y is F or Br;
formula II
Wherein, X is F, and Y is I or Br; Or X is Cl, and Y is I; Or X is Br, and Y is F or I; Or X is I, and Y is F or Br.
2. compound method according to claim 1 is characterized in that: described temperature of reaction is 0～50 ℃.
3. compound method according to claim 2 is characterized in that: described temperature of reaction is 0～30 ℃.
4. compound method according to claim 1 is characterized in that: described mol ratio is 1: 0.7～1: 1.2.
5. compound method according to claim 4 is characterized in that: described mol ratio is 1: 0.7～1: 0.99.
6. compound method according to claim 1; It is characterized in that: described solvent is methylene dichloride, chloroform, tetracol phenixin, 1,2-ethylene dichloride, 1,1; 2-trichloroethane, 1; 1,2,2-tetrachloroethane, chlorobenzene, dichlorobenzene, oil of mirbane, acetonitrile, Nitromethane 99Min., benzyl cyanide, sulfuric acid or acetic acid.
7. compound method according to claim 1 is characterized in that: when solvent was sulfuric acid or acetic acid, described temperature of reaction was 0～35 ℃.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5191105A (en) * | 1981-09-01 | 1993-03-02 | Sumitomo Chemical Company, Ltd. | Tetrahydrophthalimides, and their production and use as herbicides |
| CN1349515A (en) * | 1999-04-30 | 2002-05-15 | 宇部兴产株式会社 | Benzoazole compounds, process for the preparation thereof and herbicides |
| CN1539746A (en) * | 2003-10-29 | 2004-10-27 | 中国科学院上海有机化学研究所 | Green nitrifying method by using Hf compound to catalyze compounds of phenols and aromatic ether |
| CN1709856A (en) * | 2005-06-10 | 2005-12-21 | 中国科学院上海有机化学研究所 | Nitrofication method for catalysis of phenol and diphenyl ether compounds using metal salt |
| WO2006105262A1 (en) * | 2005-03-29 | 2006-10-05 | Icos Corporation | HETEROARYL UREA DERIVATIVES USEFUL FOR INHIBITING CHKl |
| CN101522689A (en) * | 2006-09-27 | 2009-09-02 | 欧加农股份有限公司 | Pyridooxazepine progesteron receptor modulators |
-
2006
- 2006-12-13 CN CN2006101195375A patent/CN101200429B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5191105A (en) * | 1981-09-01 | 1993-03-02 | Sumitomo Chemical Company, Ltd. | Tetrahydrophthalimides, and their production and use as herbicides |
| CN1349515A (en) * | 1999-04-30 | 2002-05-15 | 宇部兴产株式会社 | Benzoazole compounds, process for the preparation thereof and herbicides |
| CN1539746A (en) * | 2003-10-29 | 2004-10-27 | 中国科学院上海有机化学研究所 | Green nitrifying method by using Hf compound to catalyze compounds of phenols and aromatic ether |
| WO2006105262A1 (en) * | 2005-03-29 | 2006-10-05 | Icos Corporation | HETEROARYL UREA DERIVATIVES USEFUL FOR INHIBITING CHKl |
| CN1709856A (en) * | 2005-06-10 | 2005-12-21 | 中国科学院上海有机化学研究所 | Nitrofication method for catalysis of phenol and diphenyl ether compounds using metal salt |
| CN101522689A (en) * | 2006-09-27 | 2009-09-02 | 欧加农股份有限公司 | Pyridooxazepine progesteron receptor modulators |
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