JP3311840B2 - Method for halogenating aromatic compounds - Google Patents
Method for halogenating aromatic compoundsInfo
- Publication number
- JP3311840B2 JP3311840B2 JP28746893A JP28746893A JP3311840B2 JP 3311840 B2 JP3311840 B2 JP 3311840B2 JP 28746893 A JP28746893 A JP 28746893A JP 28746893 A JP28746893 A JP 28746893A JP 3311840 B2 JP3311840 B2 JP 3311840B2
- Authority
- JP
- Japan
- Prior art keywords
- amino
- trifluoromethylpyridine
- reaction
- group
- halogeno
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 29
- 230000002140 halogenating effect Effects 0.000 title claims description 26
- 150000001491 aromatic compounds Chemical class 0.000 title claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 69
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 25
- WXNPZQIRDCDLJD-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=C(C(F)(F)F)C=C1Cl WXNPZQIRDCDLJD-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 24
- RSGVKIIEIXOMPY-UHFFFAOYSA-N 5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC=C(C(F)(F)F)C=N1 RSGVKIIEIXOMPY-UHFFFAOYSA-N 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 20
- -1 halogeno aromatic compound Chemical class 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 238000006462 rearrangement reaction Methods 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 17
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 229960002317 succinimide Drugs 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
- 238000005658 halogenation reaction Methods 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 235000011054 acetic acid Nutrition 0.000 claims description 8
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- 150000003222 pyridines Chemical class 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
- QVPFLVIBWRFJDL-UHFFFAOYSA-N 3-chloro-5-nitropyridin-2-amine Chemical compound NC1=NC=C([N+]([O-])=O)C=C1Cl QVPFLVIBWRFJDL-UHFFFAOYSA-N 0.000 claims description 4
- UGSBCCAHDVCHGI-UHFFFAOYSA-N 5-nitropyridin-2-amine Chemical compound NC1=CC=C([N+]([O-])=O)C=N1 UGSBCCAHDVCHGI-UHFFFAOYSA-N 0.000 claims description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- JNVJSJWSBDBRHH-UHFFFAOYSA-N 6-(chloroamino)pyridine-3-carbonitrile Chemical compound ClNC1=CC=C(C#N)C=N1 JNVJSJWSBDBRHH-UHFFFAOYSA-N 0.000 claims description 3
- KDVBYUUGYXUXNL-UHFFFAOYSA-N 6-aminopyridine-3-carbonitrile Chemical compound NC1=CC=C(C#N)C=N1 KDVBYUUGYXUXNL-UHFFFAOYSA-N 0.000 claims description 3
- DYUJTWMAILZXEP-UHFFFAOYSA-N n-chloro-5-nitropyridin-2-amine Chemical compound [O-][N+](=O)C1=CC=C(NCl)N=C1 DYUJTWMAILZXEP-UHFFFAOYSA-N 0.000 claims description 3
- XDDIMILABMXHFG-UHFFFAOYSA-N 6-amino-5-chloropyridine-3-carbonitrile Chemical compound NC1=NC=C(C#N)C=C1Cl XDDIMILABMXHFG-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000001735 carboxylic acids Chemical group 0.000 claims 4
- 230000026030 halogenation Effects 0.000 claims 3
- 238000005660 chlorination reaction Methods 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000004811 liquid chromatography Methods 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000007795 chemical reaction product Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 15
- NXCILKVBUPHKHF-UHFFFAOYSA-N n-chloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CC=C(NCl)N=C1 NXCILKVBUPHKHF-UHFFFAOYSA-N 0.000 description 14
- 239000002994 raw material Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229950009390 symclosene Drugs 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- WDRFYIPWHMGQPN-UHFFFAOYSA-N 2-chloroisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Cl)C(=O)C2=C1 WDRFYIPWHMGQPN-UHFFFAOYSA-N 0.000 description 4
- JTZSFNHHVULOGJ-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1 JTZSFNHHVULOGJ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 4
- 229940045803 cuprous chloride Drugs 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- IQFLPMJLEMXRLW-UHFFFAOYSA-N n,3-dichloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CN=C(NCl)C(Cl)=C1 IQFLPMJLEMXRLW-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XZKZVCLLDKWOKM-UHFFFAOYSA-N 2-(trifluoromethyl)pyridin-3-amine Chemical class NC1=CC=CN=C1C(F)(F)F XZKZVCLLDKWOKM-UHFFFAOYSA-N 0.000 description 3
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical class ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 2
- WHWPBLMPBGBKHW-UHFFFAOYSA-N 5-chloro-6-(chloroamino)pyridine-3-carbonitrile Chemical compound ClNC1=NC=C(C#N)C=C1Cl WHWPBLMPBGBKHW-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- RPFFTHFDDFTZSQ-UHFFFAOYSA-N n,2-dichloro-6-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1NCl RPFFTHFDDFTZSQ-UHFFFAOYSA-N 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- HHBCEKAWSILOOP-UHFFFAOYSA-N 1,3-dibromo-1,3,5-triazinane-2,4,6-trione Chemical compound BrN1C(=O)NC(=O)N(Br)C1=O HHBCEKAWSILOOP-UHFFFAOYSA-N 0.000 description 1
- SJWMPHKDBJQBBJ-UHFFFAOYSA-N 2,3-dichloro-6-nitrophenol Chemical compound OC1=C(Cl)C(Cl)=CC=C1[N+]([O-])=O SJWMPHKDBJQBBJ-UHFFFAOYSA-N 0.000 description 1
- IZEZAMILKKYOPW-UHFFFAOYSA-N 2,4-dichloro-6-nitroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1[N+]([O-])=O IZEZAMILKKYOPW-UHFFFAOYSA-N 0.000 description 1
- UJJMLGJZQGGQAZ-UHFFFAOYSA-N 2-(fluoromethyl)pyridine Chemical compound FCC1=CC=CC=N1 UJJMLGJZQGGQAZ-UHFFFAOYSA-N 0.000 description 1
- GRBFIRPGPOFDKK-UHFFFAOYSA-N 2-(trifluoromethyl)pyridin-3-ol Chemical class OC1=CC=CN=C1C(F)(F)F GRBFIRPGPOFDKK-UHFFFAOYSA-N 0.000 description 1
- MARXMDRWROUXMD-UHFFFAOYSA-N 2-bromoisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(Br)C(=O)C2=C1 MARXMDRWROUXMD-UHFFFAOYSA-N 0.000 description 1
- CYMRPDYINXWJFU-UHFFFAOYSA-N 2-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC=C1C(O)=O CYMRPDYINXWJFU-UHFFFAOYSA-N 0.000 description 1
- VOTXWUCYIOPNNR-UHFFFAOYSA-N 2-chloro-6-nitroaniline Chemical compound NC1=C(Cl)C=CC=C1[N+]([O-])=O VOTXWUCYIOPNNR-UHFFFAOYSA-N 0.000 description 1
- ICCYFVWQNFMENX-UHFFFAOYSA-N 2-chloro-6-nitrophenol Chemical compound OC1=C(Cl)C=CC=C1[N+]([O-])=O ICCYFVWQNFMENX-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- DFJZJWFNRBPXSZ-UHFFFAOYSA-N 3,6-dichloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC(Cl)=C(C(F)(F)F)C=C1Cl DFJZJWFNRBPXSZ-UHFFFAOYSA-N 0.000 description 1
- AJPOOWWMZOPUCG-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=NC=C(C(F)(F)F)C=C1Cl AJPOOWWMZOPUCG-UHFFFAOYSA-N 0.000 description 1
- OMRCXTBFBBWTDL-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=CC(Cl)=C1 OMRCXTBFBBWTDL-UHFFFAOYSA-N 0.000 description 1
- VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 description 1
- VFXXTYGQYWRHJP-UHFFFAOYSA-N 4,4'-azobis(4-cyanopentanoic acid) Chemical compound OC(=O)CCC(C)(C#N)N=NC(C)(CCC(O)=O)C#N VFXXTYGQYWRHJP-UHFFFAOYSA-N 0.000 description 1
- BYRJSCNPUHYZQE-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=CC=C(C(F)(F)F)C=N1 BYRJSCNPUHYZQE-UHFFFAOYSA-N 0.000 description 1
- BSDDHEVOFPRSMC-UHFFFAOYSA-N 5-(trifluoromethyl)pyridin-2-amine;hydrochloride Chemical compound Cl.NC1=CC=C(C(F)(F)F)C=N1 BSDDHEVOFPRSMC-UHFFFAOYSA-N 0.000 description 1
- ZHDJWTAHGYSQQV-UHFFFAOYSA-N 5-chloro-3-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=NC=C(Cl)C=C1C(F)(F)F ZHDJWTAHGYSQQV-UHFFFAOYSA-N 0.000 description 1
- WPGLCXZKCAARBY-UHFFFAOYSA-N 5-chloro-3-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1C(F)(F)F WPGLCXZKCAARBY-UHFFFAOYSA-N 0.000 description 1
- XKMSOSLGTYIFCE-UHFFFAOYSA-N 6-chloro-3-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC(Cl)=CC=C1C(F)(F)F XKMSOSLGTYIFCE-UHFFFAOYSA-N 0.000 description 1
- FXLKGHMCRNENON-UHFFFAOYSA-N 6-chloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC=C(C(F)(F)F)C(Cl)=N1 FXLKGHMCRNENON-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 108700012364 REG1 Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NLKLJDLLFLYGPS-UHFFFAOYSA-N [3-chloro-5-(trifluoromethyl)pyridin-2-yl] hypochlorite Chemical compound FC(F)(F)C1=CN=C(OCl)C(Cl)=C1 NLKLJDLLFLYGPS-UHFFFAOYSA-N 0.000 description 1
- LMLVKOBNLWPZLU-UHFFFAOYSA-N [5-(trifluoromethyl)pyridin-2-yl] hypochlorite Chemical compound FC(F)(F)C1=CC=C(OCl)N=C1 LMLVKOBNLWPZLU-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 239000000386 donor Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- DWSBXQANUBBUCN-UHFFFAOYSA-N n,3,6-trichloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CC(Cl)=C(NCl)N=C1Cl DWSBXQANUBBUCN-UHFFFAOYSA-N 0.000 description 1
- NLLBSICVTRPRGS-UHFFFAOYSA-N n,3-dichloro-5-nitropyridin-2-amine Chemical compound [O-][N+](=O)C1=CN=C(NCl)C(Cl)=C1 NLLBSICVTRPRGS-UHFFFAOYSA-N 0.000 description 1
- YQRJIMBPNVLIEH-UHFFFAOYSA-N n,6-dichloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CC=C(NCl)N=C1Cl YQRJIMBPNVLIEH-UHFFFAOYSA-N 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- QBLHIGXDCKXUNN-UHFFFAOYSA-N n-chloro-3-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)C1=CC=CN=C1NCl QBLHIGXDCKXUNN-UHFFFAOYSA-N 0.000 description 1
- HUDSSSKDWYXKGP-UHFFFAOYSA-N n-phenylpyridin-2-amine Chemical class C=1C=CC=NC=1NC1=CC=CC=C1 HUDSSSKDWYXKGP-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- RKHXQBLJXBGEKF-UHFFFAOYSA-M tetrabutylphosphanium;bromide Chemical compound [Br-].CCCC[P+](CCCC)(CCCC)CCCC RKHXQBLJXBGEKF-UHFFFAOYSA-M 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- ZKWDCFPLNQTHSH-UHFFFAOYSA-N tribromoisocyanuric acid Chemical compound BrN1C(=O)N(Br)C(=O)N(Br)C1=O ZKWDCFPLNQTHSH-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は医薬、農薬の中間体とし
て有用な３−ハロゲノ芳香族化合物特に３−ハロゲノピ
リジン類の工業的有利な製造方法に関する。前記３−ハ
ロゲノピリジン類は例えば特開昭５６−９２２７２、特
開平４−２７０２６６、西独特許出願公開第３９２５２
３８号などの各公報にて記載された殺菌剤、殺虫剤の有
効成分であるアニリノピリジン類の中間体として有用で
ある。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an industrially advantageous process for producing 3-halogenoaromatic compounds, particularly 3-halogenopyridines, which are useful as intermediates for pharmaceuticals and agricultural chemicals. The 3-halogenopyridines are described in, for example, JP-A-56-92272, JP-A-4-270266, and West German Patent Application No. 39252.
It is useful as an intermediate of anilinopyridines which are active ingredients of fungicides and insecticides described in each gazette such as No. 38.
【０００２】[0002]
【従来の技術】従来から２−アミノ−３−クロロ−５−
トリフルオロメチルピリジンのような３−ハロゲノピリ
ジン類は種々の方法により製造することが知られてい
る。例えば特開昭５６−９７２７１公報の第６５４頁に
は２−アミノ−５−トリフルオロメチルピリジンを濃塩
酸に溶解させ、塩素ガスを吹き込んで反応させて２−ア
ミノ−３−クロロ−５−トリフルオロメチルピリジンを
製造する方法が記載されているが、この方法では目的の
２−アミノ−３−クロロ−５−トリフルオロメチルピリ
ジンが少量生成するものの多くの種類の副生物が多量に
生成し、反応生成物から目的物を良好に分離することが
できないので目的物の収率が低いために工業的実施面で
難点がある。2. Description of the Related Art Conventionally, 2-amino-3-chloro-5-
It is known that 3-halogenopyridines such as trifluoromethylpyridine are produced by various methods. For example, on page 654 of JP-A-56-97271, 2-amino-5-trifluoromethylpyridine is dissolved in concentrated hydrochloric acid, and chlorine gas is blown thereinto to cause a reaction. Although a method for producing fluoromethylpyridine is described, in this method, although the desired 2-amino-3-chloro-5-trifluoromethylpyridine is produced in a small amount, many types of by-products are produced in a large amount, Since the desired product cannot be satisfactorily separated from the reaction product, the yield of the desired product is low, which is disadvantageous in industrial practice.
【０００３】[0003]
【発明が解決しようとする課題】２−アミノ−５−トリ
フルオロメチルピリジンのようなピリジン類をハロゲン
化して目的の２−アミノ−３−クロロ−５−トリフルオ
ロメチルピリジンなどの３−ハロゲノピリジン類を製造
する前述の従来方法において副生物が余り生成せず、目
的物を良好に製造し分離できる方法の出現が求められて
いる。SUMMARY OF THE INVENTION A pyridine such as 2-amino-5-trifluoromethylpyridine is halogenated to give a desired 3-halogenopyridine such as 2-amino-3-chloro-5-trifluoromethylpyridine. There has been a demand for a method for producing and separating a target product without producing much by-products in the above-mentioned conventional method for producing a product.
【０００４】[0004]
【課題を解決するための手段】本発明者達は前述の従来
方法において特定のハロゲン化反応次いで転位反応をお
こなったところ、所期の反応が進み前述の課題を解決で
きることを見出し本発明を提案するに至った。Means for Solving the Problems The present inventors have found that when a specific halogenation reaction and a rearrangement reaction are carried out in the above-mentioned conventional method, the desired reaction proceeds and the aforementioned problems can be solved, and the present invention is proposed. I came to.
【０００５】本発明は、一般式（Ｉ）The present invention relates to a compound represented by the general formula (I):
【０００６】[0006]
【化１５】 Embedded image
【０００７】〔式中Ｘは水酸基、アミノ基またはアシル
アミノ基であり、Ｚ1 およびＺ2 は水素原子またはハロ
ゲン原子であり、ＲおよびＹは一方が水素原子、他方が
ニトロ基、シアノ基またはトリフルオロメチル基であ
り、Ｑは窒素原子または−Ｃ（Ｔ）＝基（Ｔは水素原
子、ハロゲン原子、ニトロ基、シアノ基またはトリフル
オロメチル基）である〕で表される芳香族化合物とハロ
ゲン化剤とを反応させて一般式（ＩＩ）Wherein X is a hydroxyl group, an amino group or an acylamino group, Z 1 and Z 2 are a hydrogen atom or a halogen atom, and one of R and Y is a hydrogen atom, and the other is a nitro group, a cyano group or a tri group. An aromatic compound represented by a nitrogen atom or a -C (T) = group (T is a hydrogen atom, a halogen atom, a nitro group, a cyano group or a trifluoromethyl group); Reacting the compound with a compound of the general formula (II)
【０００８】[0008]
【化１６】 Embedded image
【０００９】（式中Ｒ′およびＹ′は一方がハロゲン原
子、他方がニトロ基、シアノ基またはトリフルオロメチ
ル基であり、Ｘ、Ｚ1 、Ｚ2 およびＱは前述のとおりで
ある）で表される３−ハロゲノ芳香族化合物を製造する
方法において、前記芳香族化合物とハロゲン化剤とを反
応させて一般式（ＩＩＩ）Wherein R 'and Y' are each a halogen atom, the other is a nitro group, a cyano group or a trifluoromethyl group, and X, Z 1 , Z 2 and Q are as described above. In the method for producing a 3-halogeno aromatic compound represented by the general formula (III), the aromatic compound is reacted with a halogenating agent.
【００１０】[0010]
【化１７】 Embedded image
【００１１】〔式中Ｅは[Where E is
【００１２】[0012]
【化１８】 Embedded image
【００１３】（Ａは水素原子またはアシル基であり、Ｈ
ａｌはハロゲン原子）であり、Ｚ1 、Ｚ2 、Ｒ、Ｙおよ
びＱは前述のとおりである〕で表されるハロゲノ芳香族
化合物を生成させ、このハロゲノ芳香族化合物をプロト
ン供与体の存在下に転位反応させて前記３−ハロゲノ芳
香族化合物を生成させる方法に関する。(A is a hydrogen atom or an acyl group;
al is a halogen atom), and Z 1 , Z 2 , R, Y and Q are as defined above) to produce a halogeno-aromatic compound represented by the following formula: To produce the 3-halogeno aromatic compound.
【００１４】また本発明は、一般式（Ｉ′）The present invention also relates to a compound of the formula (I ')
【００１５】[0015]
【化１９】 Embedded image
【００１６】〔式中Ｘは水酸基、アミノ基またはアシル
アミノ基であり、Ｚ1 およびＺ2 は水素原子またはハロ
ゲン原子であり、ＲおよびＹは一方が水素原子、他方が
ニトロ基、シアノ基またはトリフルオロメチル基であ
る〕で表されるピリジン類とハロゲン化剤とを反応させ
て一般式（ＩＩ′）Wherein X is a hydroxyl group, an amino group or an acylamino group, Z 1 and Z 2 are a hydrogen atom or a halogen atom, and R and Y are one of a hydrogen atom and the other is a nitro group, a cyano group or a tri group. Which is a fluoromethyl group] with a halogenating agent to give a compound of the general formula (II ')
【００１７】[0017]
【化２０】 Embedded image
【００１８】（式中Ｒ′およびＹ′は一方がハロゲン原
子、他方がニトロ基、シアノ基またはトリフルオロメチ
ル基であり、Ｘ、Ｚ1 およびＺ2 は前述のとおりであ
る）で表される３−ハロゲノピリジン類を製造する方法
において、前記ピリジン類とハロゲン化剤とを反応させ
て一般式（ＩＩＩ′）(In the formula, one of R 'and Y' is a halogen atom, the other is a nitro group, a cyano group or a trifluoromethyl group, and X, Z 1 and Z 2 are as described above.) In the method for producing 3-halogenopyridines, the pyridines are reacted with a halogenating agent to obtain a compound represented by the general formula (III ′):
【００１９】[0019]
【化２１】 Embedded image
【００２０】〔式中Ｅは[Where E is
【００２１】[0021]
【化２２】 Embedded image
【００２２】（Ａは水素原子またはアシル基であり、Ｈ
ａｌはハロゲン原子）であり、Ｚ1 、Ｚ2 、ＲおよびＹ
は前述のとおりである〕で表されるハロゲノピリジン類
を生成させ、このハロゲノピリジン類をプロトン供与体
の存在下に転位反応させて前記３−ハロゲノピリジン類
を生成させる方法に関し、(A is a hydrogen atom or an acyl group;
al is a halogen atom), Z 1 , Z 2 , R and Y
Is as described above), and a method for producing the 3-halogenopyridines by subjecting the halogenopyridines to a rearrangement reaction in the presence of a proton donor.
【００２３】さらに本発明は、一般式（ＩＩＩ′）The present invention further relates to a compound of the formula (III ')
【００２４】[0024]
【化２３】 Embedded image
【００２５】〔式中Ｅは[Where E is
【００２６】[0026]
【化２４】 Embedded image
【００２７】（Ａは水素原子またはアシル基であり、Ｈ
ａｌはハロゲン原子）であり、Ｚ1 およびＺ2 は水素原
子またはハロゲン原子であり、ＲおよびＹは一方が水素
原子、他方がニトロ基、シアノ基またはトリフルオロメ
チル基である〕で表されるハロゲノピリジン類をプロト
ン供与体の存在下に転移反応させて一般式（ＩＩ′）(A is a hydrogen atom or an acyl group;
al is a halogen atom), Z 1 and Z 2 are a hydrogen atom or a halogen atom, and R and Y are one of a hydrogen atom and the other is a nitro group, a cyano group or a trifluoromethyl group. A halogenopyridine is subjected to a transfer reaction in the presence of a proton donor to obtain a compound of the general formula (II ′)
【００２８】[0028]
【化２５】 Embedded image
【００２９】（式中Ｒ′およびＹ′は一方がハロゲン原
子、他方がニトロ基、シアノ基またはトリフルオロメチ
ル基であり、Ｘは水酸基、アミノ基またはアシルアミノ
基であり、Ｚ1 およびＺ2 は前述のとおりである）で表
される３−ハロゲノピリジン類を製造する方法ならびに
本発明は一般式（Ｖ）(In the formula, one of R 'and Y' is a halogen atom, the other is a nitro group, a cyano group or a trifluoromethyl group, X is a hydroxyl group, an amino group or an acylamino group, and Z 1 and Z 2 are As described above), the present invention provides a method for producing a 3-halogenopyridine represented by the general formula (V)
【００３０】[0030]
【化２６】 Embedded image
【００３１】（式中Ｒ″およびＹ″は一方が水素原子ま
たはハロゲノ原子、他方がニトロ基、シアノ基またはト
リフルオロメチル基であり、Ｅ、Ｚ1 およびＺ2 は前述
のとおりである）で表されるハロゲノピリジン誘導体に
も関する。Wherein one of R ″ and Y ″ is a hydrogen atom or a halogeno atom, the other is a nitro group, a cyano group or a trifluoromethyl group, and E, Z 1 and Z 2 are as described above. It also relates to the represented halogenopyridine derivatives.
【００３２】一般式（Ｉ）〜（ＩＩＩ）、（Ｉ′）〜
（ＩＩＩ′）、（Ｖ）および後記（ＩＶ）においてＺ1
およびＺ2 で表されるハロゲン原子としては弗素、塩
素、臭素などが挙げられるが望ましくは塩素であり、Ｘ
で表されるアシルアミノ基としてはアルキルカルボニル
アミノが挙げられるが望ましくはアセチルアミノ基であ
り、またＲ′、Ｙ′、Ｒ″、Ｙ″およびＨａｌで表され
るハロゲン原子としては塩素、臭素などが挙げられるが
望ましくは塩素である。Formulas (I)-(III), (I ')-
In (III ′), (V) and (IV) below, Z 1
And the halogen atom represented by Z 2 include fluorine, chlorine, bromine and the like, preferably chlorine.
The acylamino group represented by is, for example, an alkylcarbonylamino, preferably an acetylamino group, and the halogen atom represented by R ′, Y ′, R ″, Y ″ and Hal includes chlorine, bromine and the like. And chlorine is preferred.
【００３３】前記一般式（Ｉ）で表される芳香族化合物
としては後記ピリジン類の他に２−クロロ−６−ニトロ
アニリン、２−クロロ−６−ニトロフェノールなどが挙
げられるが、ピリジン類が好ましい。前記一般式（Ｉ）
で表されるピリジン類としては例えば２−アミノ−５−
ニトロピリジン、２−アミノ−５−シアノピリジン、２
−アミノ−５−トリフルオロメチルピリジン、２−アミ
ノ−６−クロロ−５−トリフルオロメチルピリジン、２
−アミノ−３−トリフルオロメチルピリジン、２−アミ
ノ−６−クロロ−３−トリフルオロメチルピリジンなど
のアミノトリフルオロメチルピリジン類、２−ヒドロキ
シ−５−トリフルオロメチルピリジン、２−ヒドロキシ
−３−トリフルオロメチルピリジンなどのヒドロキシト
リフルオロメチルピリジン類などが挙げられるが、なか
でもアミノトリフルオロメチルピリジン類が望ましい。Examples of the aromatic compound represented by the general formula (I) include 2-chloro-6-nitroaniline and 2-chloro-6-nitrophenol in addition to pyridine described below. preferable. Formula (I)
As the pyridines represented by, for example, 2-amino-5-
Nitropyridine, 2-amino-5-cyanopyridine, 2
-Amino-5-trifluoromethylpyridine, 2-amino-6-chloro-5-trifluoromethylpyridine, 2
Aminotrifluoromethylpyridines such as -amino-3-trifluoromethylpyridine, 2-amino-6-chloro-3-trifluoromethylpyridine, 2-hydroxy-5-trifluoromethylpyridine, 2-hydroxy-3- Examples thereof include hydroxytrifluoromethylpyridines such as trifluoromethylpyridine, and among them, aminotrifluoromethylpyridines are preferable.
【００３４】前記一般式（ＩＩ）で表される３−ハロゲ
ノ芳香族化合物としては後記３−ハロゲノピリジン類の
他に２，４−ジクロロ−６−ニトロアニリン、２，４−
ジクロロ−６−ニトロフェノールなどが挙げられるが、
３−ハロゲノピリジン類が好ましい。また一般式（Ｉ
Ｉ）で表される３−ハロゲノピリジン類としては例えば
２−アミノ−３−クロロ−５−ニトロピリジン、２−ア
ミノ−３−クロロ−５−シアノピリジン、２−アミノ−
３−クロロ−５−トリフルオロメチルピリジン、２−ア
ミノ−３，６−ジクロロ−５−トリフルオロメチルピリ
ジン、２−アミノ−５−クロロ−３−トリフルオロメチ
ルピリジンなどの３−ハロゲノアミノトリフルオロメチ
ルピリジン類、２−ヒドロキシ−３−クロロ−５−トリ
フルオロメチルピリジン、２−ヒドロキシ−５−クロロ
−３−トリフルオロメチルピリジンなどの３−ハロゲノ
ヒドロキシトリフルオロメチルピリジン類などが挙げら
れるが、なかでも３−ハロゲノアミノトリフルオロメチ
ルピリジン類が望ましい。The 3-halogenoaromatic compounds represented by the general formula (II) include, in addition to the 3-halogenopyridines described below, 2,4-dichloro-6-nitroaniline,
Dichloro-6-nitrophenol and the like,
3-halogenopyridines are preferred. The general formula (I
Examples of the 3-halogenopyridines represented by I) include 2-amino-3-chloro-5-nitropyridine, 2-amino-3-chloro-5-cyanopyridine, and 2-amino-
3-halogenoaminotrifluoro such as 3-chloro-5-trifluoromethylpyridine, 2-amino-3,6-dichloro-5-trifluoromethylpyridine, 2-amino-5-chloro-3-trifluoromethylpyridine Examples include 3-halogenohydroxytrifluoromethylpyridines such as methylpyridines, 2-hydroxy-3-chloro-5-trifluoromethylpyridine, and 2-hydroxy-5-chloro-3-trifluoromethylpyridine. Among them, 3-halogenoaminotrifluoromethylpyridines are desirable.
【００３５】さらに前記一般式（ＩＩＩ）で表されるハ
ロゲノ芳香族化合物としては後記ハロゲノピリジン類の
他に２−クロロアミノ−３−クロロニトロベンゼン、２
−クロロオキシ−３−クロロニトロベンゼンなどが挙げ
られるが、ハロゲノピリジン類が好ましい。一般式（Ｉ
ＩＩ′）または（Ｖ）で表されるハロゲノピリジン類ま
たはハロゲノピリジン誘導体としてはそれぞれ、例えば
２−クロロアミノ−５−ニトロピリジン、２−クロロア
ミノ−５−シアノピリジン、２−クロロアミノ−５−ト
リフルオロメチルピリジン、２−クロロアミノ−６−ク
ロロ−５−トリフルオロメチピリジン、２−クロロアミ
ノ−３−トリフルオロメチルピリジンなどの２−ハロゲ
ノアミノトリフルオロメチルピリジン類、２−クロロア
ミノ−３−クロロ−５−ニトロピリジン、２−クロロア
ミノ−３−クロロ−５−シアノピリジン、２−クロロア
ミノ−３−クロロ−５−トリフルオロメチルピリジン、
２−クロロアミノ−３，６−ジクロロ−５−トリフルオ
ロメチルピリジンなどの２−ハロゲノアミノ−３−ハロ
ゲノトリフルオロメチルピリジン類、２−クロロオキシ
−５−トリフルオロメチルピリジン、２−クロロオキシ
−３−トリフルオロメチルピリジンなどの２−ハロゲノ
オキシトリフルオロメチルピリジン類、２−クロロオキ
シ−３−クロロ−５−トリフルオロメチルピリジンなど
の２−ハロゲノオキシ−３−ハロゲノトリフルオロメチ
ルピリジン類などが挙げられるが、なかでも２−ハロゲ
ノアミノトリフルオロメチルピリジン類、２−ハロゲノ
アミノ−３−ハロゲノトリフルオロメチルピリジン類が
望ましい。Further, as the halogeno aromatic compound represented by the general formula (III), 2-chloroamino-3-chloronitrobenzene, 2-chloroamino-3-chloronitrobenzene,
-Chlorooxy-3-chloronitrobenzene and the like, and halogenopyridines are preferable. The general formula (I
Examples of the halogenopyridines or halogenopyridine derivatives represented by II ′) or (V) include, for example, 2-chloroamino-5-nitropyridine, 2-chloroamino-5-cyanopyridine, 2-chloroamino-5- 2-halogenoaminotrifluoromethylpyridines such as trifluoromethylpyridine, 2-chloroamino-6-chloro-5-trifluoromethylpyridine, 2-chloroamino-3-trifluoromethylpyridine, 2-chloroamino-3 -Chloro-5-nitropyridine, 2-chloroamino-3-chloro-5-cyanopyridine, 2-chloroamino-3-chloro-5-trifluoromethylpyridine,
2-halogenoamino-3-halogenotrifluoromethylpyridines such as 2-chloroamino-3,6-dichloro-5-trifluoromethylpyridine, 2-chlorooxy-5-trifluoromethylpyridine, 2-chlorooxy-3- Examples include 2-halogenooxytrifluoromethylpyridines such as trifluoromethylpyridine and 2-halogenooxy-3-halogenotrifluoromethylpyridines such as 2-chlorooxy-3-chloro-5-trifluoromethylpyridine. Among them, 2-halogenoaminotrifluoromethylpyridines and 2-halogenoamino-3-halogenotrifluoromethylpyridines are desirable.
【００３６】また前記一般式（Ｉ′）で表されるピリジ
ン類は種々の方法によって製造されたものを使用し得る
が、前記アミノトルフルオロメチルピリジン類にあって
は、ハロゲノトリフルオロメチルピリジン類をアンモニ
アによりアミノ化する際に、例えば反応触媒として、塩
化第一銅、酸化第一銅などの銅触媒または第４級アンモ
ニウム塩、第４級ホスホニウム塩などの相間移動触媒な
どを使用することによって当該反応処理を一層効率的に
行なうことができる。前記触媒使用量は、例えば、ハロ
ゲノトリフルオロメチルピリジン類１モルに対して０．
００５〜０．１モル程度、望ましくは０．０１〜０．０
５モル程度である。The pyridines represented by the general formula (I ') may be those produced by various methods. Among the aminotrifluoromethylpyridines, halogenotrifluoromethylpyridines When amination is carried out with ammonia, for example, a copper catalyst such as cuprous chloride or cuprous oxide or a phase transfer catalyst such as a quaternary ammonium salt or a quaternary phosphonium salt is used as a reaction catalyst. The reaction treatment can be performed more efficiently. The amount of the catalyst used is, for example, 0.1 to 1 mole of halogenotrifluoromethylpyridines.
About 005 to 0.1 mol, desirably 0.01 to 0.0
It is about 5 mol.
【００３７】本発明方法は前記芳香族化合物とハロゲン
化剤とを攪拌し混合することにより所期の反応を進行す
ることができる。ハロゲン化剤としては前記芳香族化合
物と反応して一般式（ＩＩＩ）で表されるハロゲノ芳香
族化合物を生成するものであればいかなるものでも使用
できる。ハロゲン化剤としてＮ−ハロゲノコハク酸イミ
ドまたはＮ−ハロゲノフタル酸イミドを使用する場合、
例えばＮ−クロロコハク酸イミド、Ｎ−ブロモコハク酸
イミド、Ｎ−クロロフタル酸イミド、Ｎ−ブロモフタル
酸イミドなどが使用できるが、Ｎ−クロロコハク酸イミ
ドまたはＮ−クロロフタル酸イミドが望ましい。またハ
ロゲン化剤としてｔｅｒｔ−ブチルハイポクロライドな
どのｔｅｒｔ−ブチルハイポハライド、塩素ガス、臭素
なども使用でき、さらにハロゲン化剤としてトリハロゲ
ノイソシアヌル酸、ジハロゲノイソシアヌル酸またはそ
れらの塩も使用でき、例えばトリクロロイソシアヌル
酸、トリブロモイソシアヌル酸、ジクロロイソシアヌル
酸、ジブロモイソシアヌル酸、それらのナトリウム塩、
カリウム塩などが使用できるが、トリクロロイソシアヌ
ル酸またはジクロロイソシアヌル酸の塩が望ましい。さ
らにハロゲン化剤としては前記一般式（ＩＩ）で表され
る３−ハロゲノ芳香族化合物の２位のＸをハロゲン化し
たハロゲノ３−ハロゲノ芳香族化合物も使用できるが、
一般式（ＩＶ）In the method of the present invention, the desired reaction can be advanced by stirring and mixing the aromatic compound and the halogenating agent. Any halogenating agent can be used as long as it reacts with the aromatic compound to form a halogeno aromatic compound represented by the general formula (III). When N-halogenosuccinimide or N-halogenophthalimide is used as the halogenating agent,
For example, N-chlorosuccinimide, N-bromosuccinimide, N-chlorophthalimide, N-bromophthalimide, etc. can be used, but N-chlorosuccinimide or N-chlorophthalimide is desirable. Further, tert-butyl hypohalide such as tert-butyl hypochloride, chlorine gas, bromine and the like can be used as a halogenating agent, and trihalogeno isocyanuric acid, dihalogeno isocyanuric acid or a salt thereof can be used as a halogenating agent. Trichloroisocyanuric acid, tribromoisocyanuric acid, dichloroisocyanuric acid, dibromoisocyanuric acid, their sodium salts,
Potassium salts and the like can be used, but salts of trichloroisocyanuric acid or dichloroisocyanuric acid are desirable. Further, as the halogenating agent, a halogeno 3-halogeno aromatic compound obtained by halogenating the 2-position X of the 3-halogeno aromatic compound represented by the general formula (II) can be used,
General formula (IV)
【００３８】[0038]
【化２７】 Embedded image
【００３９】（Ｒ′、Ｙ′、Ｅ、Ｚ1 およびＺ2 は前述
のとおりである）で表されるハロゲノ３−ハロゲノピリ
ジン類を使用することが望ましく、なかでも２−クロロ
アミノ−３−クロロ−５−ニトロピリジン、２−クロロ
アミノ−３−クロロ−５−シアノピリジン、２−クロロ
アミノ−３−クロロ−５−トリフルオロメチルピリジン
などが望ましい。これらハロゲン化剤は目的とする３−
ハロゲノ芳香族化合物の生成に応じて適切なものが選択
されるが、工業的にはＮ−クロロコハク酸イミド、トリ
クロロイソシアヌル酸、ジクロロイソシアヌル酸の塩、
塩素ガス、臭素、前記一般式（ＩＶ）の化合物中クロロ
３−クロロピリジン類が望ましく、塩素ガス、臭素、ク
ロロ３−クロロピリジン類がより望ましい。[0039] (R ', Y', E , Z 1 and Z 2 is as defined above) it is desirable to use a halogeno 3-halogenopyridine expressed by, inter alia 2-chloro-Amino-3- Chloro-5-nitropyridine, 2-chloroamino-3-chloro-5-cyanopyridine, 2-chloroamino-3-chloro-5-trifluoromethylpyridine and the like are desirable. These halogenating agents are the desired 3-
An appropriate one is selected depending on the generation of the halogeno aromatic compound, but industrially N-chlorosuccinimide, trichloroisocyanuric acid, a salt of dichloroisocyanuric acid,
Chlorine gas, bromine and chloro-3-chloropyridines in the compound of the above formula (IV) are desirable, and chlorine gas, bromine and chloro-3-chloropyridines are more desirable.
【００４０】本発明方法は、通常、このハロゲン化反応
に不活性な溶媒の存在下に原料物質を溶解、懸濁ないし
分散させて反応をおこなう。その溶媒としては水：四塩
化炭素、塩化メチレン、１，２−ジクロロエタンなどの
ハロゲン化脂肪族炭化水素：ベンゼン、クロロベンゼ
ン、トルエン、シクロヘキサンなどの単環式または脂環
式芳香族炭化水素：アセトニトリル、プロピオニトリル
などのニトリル類：メタノール、エタノールなどのアル
コール類：酢酸エチル、酢酸プロピルなどのエステル
類：アセトン、メチルイソブチルケトンなどのケトン類
などが挙げられ、これらのものを一種または二種以上使
用することもできる。In the method of the present invention, the reaction is usually carried out by dissolving, suspending or dispersing the raw materials in the presence of a solvent inert to the halogenation reaction. Examples of the solvent include water: halogenated aliphatic hydrocarbons such as carbon tetrachloride, methylene chloride, and 1,2-dichloroethane: monocyclic or alicyclic aromatic hydrocarbons such as benzene, chlorobenzene, toluene, and cyclohexane: acetonitrile; Nitriles such as propionitrile: alcohols such as methanol and ethanol: esters such as ethyl acetate and propyl acetate: ketones such as acetone and methyl isobutyl ketone; one or more of these are used You can also.
【００４１】また本発明方法では２，２′−アゾビスイ
ソブチロニトリル、２−アゾビス−２−メチルブチロニ
トリル、２，２′−アゾビスイソプロピオニトリル、
４，４′−アゾビス−４−シアノ吉草酸などのアゾビス
ニトリル系化合物または過酸化ベンゾイル、３，３′−
ジメチル過酸化ベンゾイルなどの過酸化ベンゾイル系化
合物を触媒として存在させた場合、所望のハロゲン化反
応の反応速度を増進させることができる。In the method of the present invention, 2,2'-azobisisobutyronitrile, 2-azobis-2-methylbutyronitrile, 2,2'-azobisisopropionitrile,
Azobisnitrile compounds such as 4,4'-azobis-4-cyanovaleric acid or benzoyl peroxide, 3,3'-
When a benzoyl peroxide-based compound such as dimethyl benzoyl peroxide is used as a catalyst, the reaction rate of a desired halogenation reaction can be increased.
【００４２】本発明方法において原料物質としての前記
芳香族化合物、ハロゲン化剤としてのＮ−ハロゲノコハ
ク酸イミド、Ｎ−ハロゲノフタル酸イミド、ｔｅｒｔ−
ブチルハイポハライドまたは前記ハロゲノ３−ハロゲノ
芳香族化合物、溶媒および触媒の使用量はこれら物質の
種類、反応条件などの相違により異なり一概に規定でき
ないが、原料物質としての前記芳香族化合物１モル当
り、普通Ｎ−ハロゲノコハク酸イミド、Ｎ−ハロゲノフ
タル酸イミド、ｔｅｒｔ−ブチルハイポハライドまたは
前記ハロゲノ３−ハロゲノ芳香族化合物は１．０〜１．
５モルであり、溶媒は０．５〜２０重量部および触媒は
０．００１〜０．０２モルである。この場合反応温度お
よび反応時間は同様に原料物質、ハロゲン化剤の種類、
溶媒または触媒の有無、種類などの相異により異なる
が、反応は普通−２０℃〜溶媒の還流温度で０．５〜２
４時間で終了する。In the method of the present invention, the aromatic compound as a raw material, N-halogenosuccinimide, N-halogenophthalimide, tert-
The amount of the butyl hypohalide or the halogeno-3-halogeno aromatic compound, the solvent and the catalyst used may vary depending on the type of these substances, the reaction conditions and the like, and cannot be specified unconditionally. However, per mole of the aromatic compound as a raw material, Normally, N-halogenosuccinimide, N-halogenophthalimide, tert-butyl hypohalide, or the halogeno-3-halogeno aromatic compound is 1.0 to 1.
5 mol, the solvent is 0.5 to 20 parts by weight and the catalyst is 0.001 to 0.02 mol. In this case, the reaction temperature and the reaction time are similarly set for the starting material, the type of the halogenating agent,
The reaction usually varies from -20 ° C to the reflux temperature of the solvent in the range of 0.5 to 2
Finish in 4 hours.
【００４３】また本発明方法においてハロゲン化剤とし
てトリハロゲノイソシアヌル酸、ジハロゲノイソシアヌ
ル酸またはそれらの塩を用いる場合、同様にこれら物質
の使用量はその種類、反応条件などの相違により異なり
一概に規定できないが、前記芳香物化合物１モル当り、
普通トリハロゲノイソシアヌル酸またはその塩は０．３
〜１．０モル、ジハロゲノイソシアヌル酸またはその塩
は普通０．５〜１．５モル使用される。この場合反応温
度および反応時間は種々の反応条件の相異により異なる
が、反応は普通−２０℃〜溶媒の還流温度で０．５〜２
４時間で終了する。When trihalogeno isocyanuric acid, dihalogen isocyanuric acid or a salt thereof is used as a halogenating agent in the method of the present invention, the amounts of these substances used also vary depending on the type, reaction conditions and the like, and are generally defined. Although not possible, per mole of the aromatic compound,
Usually, trihalogeno isocyanuric acid or its salt is 0.3
The dihalogeno isocyanuric acid or its salt is usually used in an amount of 0.5 to 1.5 mol. In this case, the reaction temperature and the reaction time vary depending on various reaction conditions, but the reaction is usually carried out at -20 ° C to the reflux temperature of the solvent for 0.5 to 2 hours.
Finish in 4 hours.
【００４４】さらに本発明方法においてハロゲン化剤と
して塩素ガスまたは臭素を用いる場合、その使用量は同
様に一概に規定できないが、前記芳香族化合物１モル当
り、普通塩素ガスまたは臭素を０．５〜１．０モル使用
される。この場合の反応温度および反応時間も同様に一
概に規定できないが、反応は普通−２０℃ないし溶媒の
還流温度、望ましくは０℃〜溶媒の還流温度で０．５〜
２４時間で終了する。また２−アミノ−５−トリフルオ
ロメチルピリジンを塩素ガスを用いて塩素化する場合は
同様に一概に規定できないが、反応は普通−２０℃ない
し２０℃で行なわれる。かくして本発明方法では前記一
般式（ＩＩＩ）で表されるハロゲノ芳香族化合物を良好
に生成することができる。また前記一般式（ＩＶ）で表
されるハロゲノ３−ハロゲノピリジン類は前記ピリジン
類のハロゲン化方法の場合と殆んど同様にして製造され
る。Further, when chlorine gas or bromine is used as a halogenating agent in the method of the present invention, the amount of the chlorine gas or bromine can not be specified unconditionally. 1.0 mole is used. In this case, the reaction temperature and the reaction time cannot be specified unconditionally, but the reaction is usually carried out at -20 ° C to the reflux temperature of the solvent, preferably 0 ° C to 0.5 to the reflux temperature of the solvent.
Ends in 24 hours. When 2-amino-5-trifluoromethylpyridine is chlorinated using chlorine gas, the reaction cannot be generally specified, but the reaction is usually carried out at -20 ° C to 20 ° C. Thus, according to the method of the present invention, the halogeno aromatic compound represented by the general formula (III) can be favorably produced. The halogeno-3-halogenopyridines represented by the general formula (IV) are produced almost in the same manner as in the method for halogenating pyridines.
【００４５】次に本発明方法においては、前記ハロゲノ
芳香族化合物をプロトン供与体の存在下に転位させる転
位反応がおこなわれる。この転位反応の反応温度および
反応時間は同様に原料物質の種類、プロトン供与体、溶
媒または触媒の有無、種類などの相違により異なるが、
反応は普通０℃〜溶媒の還流温度、望ましくは２０℃〜
溶媒の還流温度で０．５〜２４時間で終了し、目的の３
−ハロゲノ芳香族化合物を良好に生成することができ
る。前記プロトン供与体としては蟻酸、酢酸、プロピオ
ン酸、蓚酸、コハク酸、安息香酸などのカルボン酸類、
コハク酸イミド、フタル酸イミド、イソシアヌル酸など
が挙げられるが蟻酸、酢酸およびプロピオン酸からなる
群から選ばれた少くとも一種のカルボン酸が望ましい。Next, in the method of the present invention, a rearrangement reaction for rearranging the halogeno aromatic compound in the presence of a proton donor is performed. The reaction temperature and reaction time of this rearrangement reaction also vary depending on the type of the raw materials, the presence or absence of a proton donor, a solvent or a catalyst, and the type, but
The reaction is usually carried out at 0 ° C. to the reflux temperature of the solvent, preferably at 20 ° C.
The reaction is completed in 0.5 to 24 hours at the reflux temperature of the solvent,
A halogeno-aromatic compound can be produced favorably; As the proton donor, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, carboxylic acids such as benzoic acid,
Examples thereof include succinimide, phthalimide, and isocyanuric acid, and at least one carboxylic acid selected from the group consisting of formic acid, acetic acid, and propionic acid is preferable.
【００４６】ハロゲン化剤としてＮ−ハロゲノコハク酸
イミド、Ｎ−ハロゲノフタル酸イミド、トリハロゲノイ
ソシアヌル酸、ジハロゲノイソシアヌル酸またはそれら
の塩を使用する場合、それぞれコハク酸イミド、フタル
酸イミドまたはイソシアヌル酸が反応系内に副生しプロ
トン供与体として作用するので、プロトン供与体を別に
添加したりあるいは特別ハロゲン化反応と転位反応とを
分けておこなう必要はない。しかしながらハロゲン化剤
として塩素ガス、臭素、ｔｅｒｔ−ブチルハイポハライ
ド、前記ハロゲノ３−ハロゲノ芳香族化合物などを使用
する場合、プロトン供与体を前記ハロゲノ芳香族化合物
１モル当り少くとも０．０１モル以上、望ましくは０．
０１〜０．２モル添加する。この場合、転位反応は普通
０℃〜溶媒の還流温度で０．５〜２４時間で終了する。When N-halogenosuccinimide, N-halogenophthalimide, trihalogenoisocyanuric acid, dihalogenoisocyanuric acid or a salt thereof is used as the halogenating agent, succinimide, phthalimide or isocyanuric acid is used, respectively. Is produced as a by-product in the reaction system and acts as a proton donor. Therefore, it is not necessary to separately add a proton donor or separately perform a special halogenation reaction and a rearrangement reaction. However, when chlorine gas, bromine, tert-butyl hypohalide, the halogeno 3-halogeno aromatic compound, or the like is used as the halogenating agent, the proton donor is used in an amount of at least 0.01 mol per mol of the halogeno aromatic compound, Preferably, 0.
01-0.2 mol is added. In this case, the rearrangement reaction is usually completed at 0 ° C. to the reflux temperature of the solvent in 0.5 to 24 hours.
【００４７】反応終了後、反応生成物は通常の精製、分
離手段に供することにより目的物を分離することができ
るが、Ｎ−ハロゲノコハク酸イミド、Ｎ−ハロゲノフタ
ル酸イミド、トリハロゲノイソシアヌル酸、ジハロゲノ
イソシアヌル酸またはそれらの塩を用いて前記芳香族化
合物をハロゲン化した場合、一般に反応生成物を冷却後
反応で副生したコハク酸イミド、フタル酸イミドまたは
イソシアヌル酸を濾過し、回収し、一方オイル層は酸性
水溶液を加えて目的物の塩を生成し、水層を中和して目
的物を分離すればよい。かくして目的物は例えば収率７
０％以上で取得することができる。After completion of the reaction, the desired product can be separated by subjecting the reaction product to ordinary purification and separation means, but N-halogenosuccinimide, N-halogenophthalimide, trihalogenisocyanuric acid, When the aromatic compound is halogenated using dihalogeno isocyanuric acid or a salt thereof, the succinimide, phthalimide or isocyanuric acid by-produced in the reaction is generally cooled and cooled, and the reaction product is recovered and collected. On the other hand, the oil layer may be formed by adding an acidic aqueous solution to form a salt of the target substance, neutralizing the aqueous layer and separating the target substance. Thus, the desired product has a yield of 7 for example.
It can be obtained at 0% or more.
【００４８】また回収したコハク酸イミド、フタル酸イ
ミドまたはイソシアヌル酸に関しては反応生成物を冷却
後、水酸化ナトリウム、水酸化カリウムなどのアルカリ
性水溶液を加えて水層とオイル層とに分液し、水層に塩
素ガスを吹き込んだりあるいは臭素を滴下してＮ−クロ
ロコハク酸イミド、Ｎ−ブロモコハク酸イミド、Ｎ−ク
ロロフタル酸イミド、トリクロロイソシアヌル酸、ジク
ロロイソシアヌル酸、それらの塩などを生成し、これを
リサイクルして使用することもできる。For the recovered succinimide, phthalic imide or isocyanuric acid, the reaction product is cooled, and then an aqueous alkaline solution such as sodium hydroxide or potassium hydroxide is added thereto to separate into an aqueous layer and an oil layer. Blowing chlorine gas or dropping bromine into the aqueous layer produces N-chlorosuccinimide, N-bromosuccinimide, N-chlorophthalimide, trichloroisocyanuric acid, dichloroisocyanuric acid, salts thereof, and the like. It can be recycled for use.
【００４９】さらに前記芳香族化合物を、塩素ガス、臭
素を用いてハロゲン化した場合、前記芳香族化合物のハ
ロゲン化水素酸塩を副生するが、このものはアルカリ性
物質で処理後芳香族化合物を生成し、これを原料として
例えば次のごとくリサイクルして使用することもでき
る。前述の方法により製造した前記３−ハロゲノ芳香族
化合物を、前記一般式（Ｉ）で表される芳香族化合物の
ハロゲン化反応の場合と同様にハロゲン化してハロゲノ
３−ハロゲノ芳香族化合物を生成させ、次いでこのハロ
ゲノ３−ハロゲノ芳香族化合物を用いて前記一般式
（Ｉ）で表される芳香族化合物をハロゲン化して前記一
般式（ＩＩＩ）で表されるハロゲノ芳香族化合物を生成
させ、このハロゲノ芳香族化合物を転位反応させて３−
ハロゲノ芳香族化合物を製造する。このような３−ハロ
ゲノ芳香族化合物の製造方法と前記３−ハロゲノ芳香族
化合物を塩素ガス、臭素でハロゲン化する場合に副生す
る３−ハロゲノ芳香族化合物のハロゲン化水素酸塩を適
切なアルカリ性物質による処理方法とを組合せることに
より、理論的には２倍当量の３−ハロゲノ芳香族化合物
と当量の芳香族化合物から３倍当量の３−ハロゲノ芳香
族化合物を製造することができる。前述のごとく得られ
た３倍当量の３−ハロゲノ芳香族化合物の一部をリサイ
クルしながら、前記ハロゲン化反応および転位反応を順
次行ない、目的の３−ハロゲノ芳香族化合物を工業的有
利に製造することができる。Further, when the aromatic compound is halogenated using chlorine gas or bromine, a hydrohalide of the aromatic compound is produced as a by-product, which is treated with an alkaline substance to convert the aromatic compound. It can be produced and recycled as a raw material, for example, as follows. The 3-halogeno aromatic compound produced by the method described above is halogenated in the same manner as in the case of the halogenation reaction of the aromatic compound represented by the general formula (I) to produce a halogeno 3-halogeno aromatic compound. Then, using the halogeno-3-halogeno aromatic compound, the aromatic compound represented by the general formula (I) is halogenated to form a halogeno aromatic compound represented by the general formula (III). The aromatic compound undergoes a rearrangement reaction to give 3-
Produce halogeno aromatic compounds. A method for producing such a 3-halogeno-aromatic compound, and a method for producing a 3-halogeno-aromatic compound by using a hydrogen halide of a 3-halogeno-aromatic compound which is by-produced when halogenating the 3-halogeno-aromatic compound with chlorine gas or bromine, is appropriately alkalized. By combining with a treatment method using a substance, it is theoretically possible to produce a 3-fold equivalent of a 3-halogeno aromatic compound from a 2-fold equivalent of a 3-halogeno aromatic compound and an equivalent of an aromatic compound. The halogenation reaction and the rearrangement reaction are sequentially performed while recycling a part of the three-fold equivalent 3-halogeno aromatic compound obtained as described above to produce the desired 3-halogeno aromatic compound in an industrially advantageous manner. be able to.
【００５０】[0050]
【実施例】以下に本発明の実施例を記載するが、本発明
の方法は決してこれら記載により限定されるものではな
い。 実施例１ （１）内容積２リットルのＳＵＳ−３１６製オートクレ
ーブに、２−クロロ−５−トリフルオロメチルピリジン
３６３ｇ（２．０モル）、塩化第一銅 １９．８ｇ
（０．２モル）、４０％アンモニア水溶液１２７５ｇ
（ＮＨ3 にして３０．０モル）を加え、１２０℃で１６
時間加熱、攪拌して反応を行なった。反応終了後室温に
冷却し、アンモニア水層とオイル層とを分液したとこ
ろ、原料の２−クロロ−５−トリフルオロメチルピリジ
ン１．５％、２−アミノ−５−トリフルオロメチルピリ
ジン９１％（液体クロマトグラフィーによる分析）を含
むオイル３３５ｇが得られた。さらにこのオイルを減圧
下で蒸留したところ、２−アミノ−５−トリフルオロメ
チルピリジン２７８ｇ（融点４２．５℃、液体クロマト
グラフィーによる純度９９％、収率８５％）が得られ
た。EXAMPLES Examples of the present invention will be described below, but the method of the present invention is by no means limited by these descriptions. Example 1 (1) 363 g (2.0 mol) of 2-chloro-5-trifluoromethylpyridine and 19.8 g of cuprous chloride were placed in a 2 liter SUS-316 autoclave.
(0.2 mol), 1275 g of 40% aqueous ammonia solution
(30.0 mol in terms of NH 3 ) and added at 120 ° C.
The reaction was carried out by heating and stirring for hours. After completion of the reaction, the mixture was cooled to room temperature, and the aqueous ammonia layer and the oil layer were separated. As a result, 2-chloro-5-trifluoromethylpyridine 1.5% as raw material and 2-amino-5-trifluoromethylpyridine 91% 335 g of oil containing (analysis by liquid chromatography) were obtained. The oil was further distilled under reduced pressure to obtain 278 g of 2-amino-5-trifluoromethylpyridine (melting point: 42.5 ° C, purity by liquid chromatography: 99%, yield: 85%).
【００５１】（２）攪拌機、温度計および還流冷却管の
付した３００ml四つ口フラスコに、前述の工程に準じて
調整された２−アミノ−５−トリフルオロメチルピリジ
ン１６．２ｇ（０．１モル）、Ｎ−クロロコハク酸イミ
ド１６．７ｇ（０．１２５モル）およびアセトニトリル
１５０ｇを加え、５０℃で５時間加熱攪拌して反応を行
なった。反応途中に２−クロロアミノ−５−トリフルオ
ロメチルピリジンの生成が確認された。反応終了後アセ
トニトリルを留去し、残った反応物中に、１０％水酸化
ナトリウム水溶液１００ｇおよび塩化メチレン１００ｇ
を加えて攪拌した。水層と塩化メチレン層を分液し、塩
化メチレン層を濃縮したところ、２−アミノ−３−クロ
ロ−５−トリフルオロメチルピリジン８５％、原料の２
−アミノ−５−トリフルオロメチルピリジン２％を含む
黄色結晶２０．２ｇ（２−アミノ−３−クロロ−５−ト
リフルオロメチルピリジンの収率：８７．４％）が得ら
れた。(2) In a 300 ml four-necked flask equipped with a stirrer, a thermometer and a reflux condenser, 16.2 g (0.1%) of 2-amino-5-trifluoromethylpyridine prepared according to the above-mentioned steps was added. Mol), 16.7 g (0.125 mol) of N-chlorosuccinimide and 150 g of acetonitrile, and the mixture was heated and stirred at 50 ° C. for 5 hours to carry out a reaction. Generation of 2-chloroamino-5-trifluoromethylpyridine was confirmed during the reaction. After completion of the reaction, acetonitrile was distilled off, and 100 g of a 10% aqueous sodium hydroxide solution and 100 g of methylene chloride were added to the remaining reaction product.
Was added and stirred. The aqueous layer and the methylene chloride layer were separated, and the methylene chloride layer was concentrated. 2-amino-3-chloro-5-trifluoromethylpyridine 85%,
20.2 g of yellow crystals containing 2% of -amino-5-trifluoromethylpyridine (yield of 2-amino-3-chloro-5-trifluoromethylpyridine: 87.4%) were obtained.
【００５２】実施例２ （１）実施例１の工程（１）において塩化第一銅１９．
８ｇ（０．２モル）に代えて、テトラ−ｎ−ブチルアン
モニウムブロマイド３２．２ｇ（０．１モル）を用いた
以外は実施例１の工程（１）と同様にして反応、後処理
を行ない、２−アミノ−５−トリフルオロメチルピリジ
ン２８４ｇ（液体クロマトグラフィーによる純度９９
％、収率８７％）が得られた。Example 2 (1) In the step (1) of Example 1, cuprous chloride was used.
The reaction and post-treatment were carried out in the same manner as in step (1) of Example 1 except that 32.2 g (0.1 mol) of tetra-n-butylammonium bromide was used instead of 8 g (0.2 mol). 284 g of 2-amino-5-trifluoromethylpyridine (purity 99 by liquid chromatography)
%, Yield 87%).
【００５３】（２）実施例１と同様の３００ml四つ口フ
ラスコに、前述の工程に準じて調整された２−アミノ−
５−トリフルオロメチルピリジン１６．２ｇ（０．１モ
ル）、Ｎ−クロロコハク酸イミド１６．７ｇ（０．１２
５モル）および塩化メチレン１５０ｇを加え、４０℃で
２４時間加熱攪拌して反応を行なった。反応途中に２−
クロロアミノ−５−トリフルオロメチルピリジンの生成
が確認された。反応終了後、塩化メチレンを留去した。
コハク酸イミドと目的とする生成物と分離するため、残
った反応物中にジエチルエーテル１５０ｇを入れ、攪拌
した。析出したコハク酸イミドを濾別し、ジエチルエー
テル液を濃縮したところ、２−アミノ−３−クロロ−５
−トリフルオロメチルピリジン８９％、原料の２−アミ
ノ−５−トリフルオロメチルピリジン０．３％を含む黄
色結晶１８．２ｇ（２−アミノ−３−クロロ−５−トリ
フルオロメチルピリジンの収率：８２．４％）が得られ
た。また、濾過して得られたコハク酸イミドは乾燥後１
１．５ｇ（ガスクロマトグラフィーによる純度９８％、
回収率：９３％）であった。(2) Into the same 300 ml four-necked flask as in Example 1, 2-amino-adjusted according to the above-described steps.
16.2 g (0.1 mol) of 5-trifluoromethylpyridine, 16.7 g (0.12 g) of N-chlorosuccinimide
5 mol) and 150 g of methylene chloride, and the mixture was heated and stirred at 40 ° C. for 24 hours to carry out a reaction. 2- during the reaction
Formation of chloroamino-5-trifluoromethylpyridine was confirmed. After completion of the reaction, methylene chloride was distilled off.
To separate the succinimide from the desired product, 150 g of diethyl ether was added to the remaining reaction product and stirred. The precipitated succinimide was filtered off and the diethyl ether solution was concentrated to give 2-amino-3-chloro-5.
18.2 g of a yellow crystal containing 89% of trifluoromethylpyridine and 0.3% of raw material 2-amino-5-trifluoromethylpyridine (yield of 2-amino-3-chloro-5-trifluoromethylpyridine: 82.4%). The succinimide obtained by filtration is dried and dried for 1 hour.
1.5 g (purity 98% by gas chromatography,
(Recovery rate: 93%).
【００５４】実施例３ （１）実施例１の工程（１）において塩化第一銅１９．
８ｇ（０．２モル）に代えて、テトラ−ｎ−ブチルホス
ホニウムブロマイド３３．９ｇ（０．１モル）を用いた
以外は、実施例１の工程（１）と同様にして反応、後処
理を行ない、２−アミノ−５−トリフルオロメチルピリ
ジン２８８ｇ（液体クロマトグラフィーによる純度９９
％、収率８８％）が得られた。Example 3 (1) In the step (1) of Example 1, cuprous chloride was used.
The reaction and post-treatment were carried out in the same manner as in step (1) of Example 1, except that 33.9 g (0.1 mol) of tetra-n-butylphosphonium bromide was used instead of 8 g (0.2 mol). 288 g of 2-amino-5-trifluoromethylpyridine (purity 99 by liquid chromatography).
%, Yield 88%).
【００５５】（２）実施例１と同様の３００mlの四つ口
フラスコに、前述の工程に準じて調製された２−アミノ
−５−トリフルオロメチルピリジン１６．２ｇ（０．１
モル）、Ｎ−クロロコハク酸イミド１６．７ｇ（０．１
２５モル）および１，２−ジクロロエタン１５０ｇを加
え、８０℃で１時間加熱、攪拌して反応を行なった。反
応途中に２−クロロアミノ−５−トリフルオロメチルピ
リジンの生成が確認された。反応終了後、室温まで冷却
し、水１００ｇを加えて攪拌した。水層とオイル層を分
液し、水層の水を減圧下で留去したところ、コハク酸イ
ミドの白色結晶１０．４ｇ（ガスクロマトグラフィーに
よる純度９８．８％、回収率：８４％）が得られた。(2) Into the same 300 ml four-necked flask as in Example 1, 16.2 g (0.1%) of 2-amino-5-trifluoromethylpyridine prepared according to the aforementioned steps.
Mol), 16.7 g of N-chlorosuccinimide (0.1
25 mol) and 150 g of 1,2-dichloroethane, and the mixture was heated and stirred at 80 ° C. for 1 hour to carry out a reaction. Generation of 2-chloroamino-5-trifluoromethylpyridine was confirmed during the reaction. After completion of the reaction, the mixture was cooled to room temperature, 100 g of water was added, and the mixture was stirred. The aqueous layer and the oil layer were separated, and water in the aqueous layer was distilled off under reduced pressure. As a result, 10.4 g of white crystals of succinimide (purity 98.8% by gas chromatography, recovery: 84%) were obtained. Obtained.
【００５６】一方、分液で得られたオイル層に、２０％
塩酸水溶液を加えて攪拌した。水層とオイル層を分液
し、水層を２５％水酸化ナトリウム水溶液を用い中和し
た。析出した微黄色結晶を濾過し乾燥したところ、１
５．４ｇの２−アミノ−３−クロロ−５−トリフルオロ
メチルピリジン（液体クロマトグラフィーによる純度９
６％、収率：７５％）が得られた。On the other hand, 20% was added to the oil layer obtained by liquid separation.
An aqueous hydrochloric acid solution was added and stirred. The aqueous layer and the oil layer were separated, and the aqueous layer was neutralized using a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried.
5.4 g of 2-amino-3-chloro-5-trifluoromethylpyridine (purity 9 by liquid chromatography)
6%, yield: 75%).
【００５７】実施例４ 実施例３において溶媒の１，２−ジクロロエタン１５０
ｇに代えてベンゼン１５０ｇを用い、さらに２，２′−
アゾビスイソブチロニトリル０．１ｇを加えた以外は、
実施例３と同様にして反応、後処理を行なった。コハク
酸イミドの得量は１０．９ｇ（ガスクロマトグラフィー
による純度は９８．７％、回収率：８８％）であり、２
−アミノ−３−クロロ−５−トリフルオロメチルピリジ
ンの得量は１５．９ｇ（液体クロマトグラフィーによる
純度９６％、収率：７８％）であった。Example 4 In Example 3, 1,2-dichloroethane 150 as a solvent was used.
g, 150 g of benzene was used, and 2,2'-
Except for adding 0.1 g of azobisisobutyronitrile,
Reaction and post-treatment were carried out in the same manner as in Example 3. The yield of succinimide was 10.9 g (purity by gas chromatography 98.7%, recovery: 88%).
The amount of -amino-3-chloro-5-trifluoromethylpyridine obtained was 15.9 g (purity 96% by liquid chromatography, yield: 78%).
【００５８】実施例５ 実施例３において溶媒の１，２−ジクロロエタン１５０
ｇに代えてトルエン１５０ｇを用いた以外は、実施例３
と同様にして反応、後処理を行なった。コハク酸イミド
の得量は１１．０ｇ（ガスクロマトグラフィーによる純
度は９８．７％、回収率：８８％）であり、２−アミノ
−３−クロロ−５−トリフルオロメチルピリジンの得量
は１６．０ｇ（液体クロマトグラフィーによる純度９７
％、収率：７９％）であった。Example 5 In Example 3, the solvent 1,2-dichloroethane 150 was used.
Example 3 except that 150 g of toluene was used instead of g.
Reaction and post-treatment were carried out in the same manner as described above. The yield of succinimide was 11.0 g (purity by gas chromatography: 98.7%, recovery: 88%), and the yield of 2-amino-3-chloro-5-trifluoromethylpyridine was 16 0.0 g (purity 97 by liquid chromatography)
%, Yield: 79%).
【００５９】実施例６ 攪拌機、温度計および還流冷却管の付した３００ml四つ
口フラスコに、前記実施例１の工程（１）に準じて調製
された２−アミノ−５−トリフルオロメチルピリジン１
６．２ｇ（０．１モル）、トリクロロイソシアヌル酸
８．８ｇ（０．０３８モル）およびアセトニトリル１５
０ｇを加え、６０℃で１時間加熱して反応を行なった。
反応途中に２−クロロアミノ−５−トリフルオロメチル
ピリジンの生成が確認された。反応終了後冷却し、析出
したイソシアヌル酸を濾過した。アセトニトリル液を濃
縮したところ、２−アミノ−３−クロロ−５−トリフル
オロメチルピリジン９２．１％、原料の２−アミノ−５
−トリフルオロメチルピリジン０．６％を含む黄色結晶
１９．９ｇ（２−アミノ−３−クロロ−５−トリフルオ
ロメチルピリジンの収率：９３．３％）が得られた。Example 6 In a 300 ml four-necked flask equipped with a stirrer, a thermometer and a reflux condenser, 2-amino-5-trifluoromethylpyridine 1 prepared according to the step (1) of Example 1 was added.
6.2 g (0.1 mol), 8.8 g (0.038 mol) of trichloroisocyanuric acid and acetonitrile 15
0 g was added, and the mixture was heated at 60 ° C. for 1 hour to carry out a reaction.
Generation of 2-chloroamino-5-trifluoromethylpyridine was confirmed during the reaction. After completion of the reaction, the mixture was cooled, and the precipitated isocyanuric acid was filtered. When the acetonitrile solution was concentrated, 92.1% of 2-amino-3-chloro-5-trifluoromethylpyridine was obtained, and 2-amino-5 as a raw material was obtained.
19.9 g of yellow crystals containing 0.6% of -trifluoromethylpyridine (yield of 2-amino-3-chloro-5-trifluoromethylpyridine: 93.3%) were obtained.
【００６０】さらに、この黄色結晶に、２０％塩酸水溶
液１００ｇとトルエン７５ｇを加えて攪拌した。水層と
オイル層を分液し、水層を２５％水酸化ナトリウム水溶
液を用い中和した。析出した微黄色結晶を濾過し、乾燥
したところ、１５．９ｇの２−アミノ−３−クロロ−５
−トリフルオロメチルピリジン（液体クロマトグラフィ
ーによる純度９６％、収率７７．７％）が得られた。ま
た、濾過して得られたイソシアヌル酸は乾燥後４．７ｇ
（回収率：９６％）であった。Further, 100 g of a 20% aqueous hydrochloric acid solution and 75 g of toluene were added to the yellow crystals and stirred. The aqueous layer and the oil layer were separated, and the aqueous layer was neutralized using a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried to obtain 15.9 g of 2-amino-3-chloro-5.
-Trifluoromethylpyridine (purity 96% by liquid chromatography, yield 77.7%) was obtained. The isocyanuric acid obtained by filtration is 4.7 g after drying.
(Recovery rate: 96%).
【００６１】実施例７ 実施例１と同様の３００ml四つ口フラスコに、前記実施
例１の工程（１）に準じて調製された２−アミノ−５−
トリフルオロメチルピリジン１６．２ｇ（０．１モ
ル）、トリクロロイソシアヌル酸１０．１ｇ（０．０４
３モル）およびトルエン１５０ｇを加え、１１０℃で３
時間加熱、攪拌して反応を行なった。反応途中に２−ク
ロロアミノ−５−トリフルオロメチルピリジンの生成が
確認された。反応終了後、室温まで冷却し、２５％水酸
化ナトリウム水溶液１００ｇを加えて攪拌した。水層と
オイル層を分液し、オイル層に２０％塩酸水溶液を加え
て攪拌した。さらに水層とオイル層を分液し、水層を２
５％水酸化ナトリウム水溶液を用い中和した。析出した
微黄色結晶を濾過し、乾燥したところ、１７．６ｇの２
−アミノ−３−クロロ−５−トリフルオロメチルピリジ
ン（液体クロマトグラフィーによる純度９５％、収率８
５％）が得られた。Example 7 In a 300 ml four-necked flask similar to that of Example 1, 2-amino-5 prepared according to the step (1) of Example 1 was used.
16.2 g (0.1 mol) of trifluoromethylpyridine, 10.1 g (0.04 g) of trichloroisocyanuric acid
3 mol) and 150 g of toluene.
The reaction was carried out by heating and stirring for hours. Generation of 2-chloroamino-5-trifluoromethylpyridine was confirmed during the reaction. After completion of the reaction, the mixture was cooled to room temperature, 100 g of a 25% aqueous sodium hydroxide solution was added, and the mixture was stirred. The aqueous layer and the oil layer were separated, and a 20% aqueous hydrochloric acid solution was added to the oil layer and stirred. Further, the aqueous layer and the oil layer are separated, and the aqueous layer is
Neutralization was performed using a 5% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried to obtain 17.6 g of 2
-Amino-3-chloro-5-trifluoromethylpyridine (purity 95% by liquid chromatography, yield 8
5%).
【００６２】実施例８ 実施例１と同様の３００ml四つ口フラスコに、２−アミ
ノ−５−トリフルオロメチルピリジン１６．２ｇ（０．
１モル）およびトルエン１５０ｇを加え、２０℃で攪拌
しながら、３０％ジクロロイソシアヌル酸ナトリウム水
溶液４２．２ｇ（ジクロロイソシアヌル酸ナトリウム
０．０５７５モル）を１時間にわたって滴下した。滴下
後反応物を８０℃に加熱し、攪拌しながら反応を１０時
間行なった。反応途中に２−クロロアミノ−５−トリフ
ルオロメチルピリジンの生成が確認された。反応終了
後、室温まで冷却し、水層とオイル層を分液した。オイ
ル層に２０％塩酸水溶液を加えて攪拌した。さらに水層
とオイル層を分液し、水層を２５％水酸化ナトリウム水
溶液を用い中和した。析出した微黄色結晶を濾過し、乾
燥したところ、１５．７ｇの２−アミノ−３−クロロ−
５−トリフルオロメチルピリジン（液体クロマトグラフ
ィーによる純度９６％、収率７７％）が得られた。Example 8 Into the same 300 ml four-necked flask as in Example 1, 16.2 g (0.2 g) of 2-amino-5-trifluoromethylpyridine was added.
1 mol) and 150 g of toluene, and 42.2 g of a 30% aqueous sodium dichloroisocyanurate solution (0.0575 mol of sodium dichloroisocyanurate) was added dropwise over 1 hour while stirring at 20 ° C. After the dropwise addition, the reaction product was heated to 80 ° C., and the reaction was carried out for 10 hours while stirring. Generation of 2-chloroamino-5-trifluoromethylpyridine was confirmed during the reaction. After the completion of the reaction, the mixture was cooled to room temperature, and the aqueous layer and the oil layer were separated. A 20% hydrochloric acid aqueous solution was added to the oil layer and stirred. Further, the aqueous layer and the oil layer were separated, and the aqueous layer was neutralized using a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried, yielding 15.7 g of 2-amino-3-chloro-
5-trifluoromethylpyridine (96% purity by liquid chromatography, 77% yield) was obtained.
【００６３】実施例９ 実施例１と同様の３００ml四つ口フラスコに、２−アミ
ノ−５−トリフルオロメチルピリジン１６．２ｇ（０．
１モル）、Ｎ−クロロフタル酸イミド２０．９ｇ（０．
１１５モル）およびトルエン１５０ｇを加え、８０℃で
１時間加熱、攪拌して反応を行なった。反応途中に２−
クロロアミノ−５−トリフルオロメチルピリジンの生成
が確認された。反応終了後、室温まで冷却し、２５％水
酸化ナトリウム水溶液５０ｇを加えて攪拌した。さらに
水層とオイル層を分液し、オイル層に２０％塩酸水溶液
を加えて攪拌した。水層とオイル層を分液し、水層を２
５％水酸化ナトリウム水溶液を用い中和した。析出した
微黄色結晶を濾過し、乾燥したところ、１７．５ｇの２
−アミノ−３−クロロ−５−トリフルオロメチルピリジ
ン（液体クロマトグラフィーによる純度９７％、収率８
６％）が得られた。Example 9 Into the same 300 ml four-necked flask as in Example 1, 16.2 g of 2-amino-5-trifluoromethylpyridine (0.
1 mol), 20.9 g of N-chlorophthalimide (0.
115 mol) and 150 g of toluene, and the mixture was heated and stirred at 80 ° C. for 1 hour to carry out a reaction. 2- during the reaction
Formation of chloroamino-5-trifluoromethylpyridine was confirmed. After completion of the reaction, the mixture was cooled to room temperature, 50 g of a 25% aqueous sodium hydroxide solution was added, and the mixture was stirred. Further, the aqueous layer and the oil layer were separated, and a 20% aqueous hydrochloric acid solution was added to the oil layer, followed by stirring. Separate the aqueous layer and the oil layer,
Neutralization was performed using a 5% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried to obtain 17.5 g of 2
-Amino-3-chloro-5-trifluoromethylpyridine (purity 97% by liquid chromatography, yield 8)
6%).
【００６４】実施例１０ 実施例１と同様の３００ml四つ口フラスコに、２−アミ
ノ−５−トリフルオロメチルピリジン１６．２ｇ（０．
１モル）およびトルエン１５０ｇを加え、０〜５℃に冷
却し攪拌しながらトリクロロイソシアヌル酸１０．１ｇ
（０．０４３モル）を１時間にわたって分割添加した。
添加後、同温度で３時間攪拌して反応を行なった。反応
物を液体クロマトグラフィーを用いて分析したところ、
２−クロロアミノ−５−トリフルオロメチルピリジンが
９１％、２−アミノ−３−クロロ−５−トリフルオロメ
チルピリジンが６％生成していた。その後、反応物を８
０℃に加熱し、攪拌しながら転位反応を２時間行なっ
た。反応物を液体クロマトグラフィーを用いて分析した
ところ、２−クロロアミノ−５−トリフルオロメチルピ
リジンのピークは消失しており、２−アミノ−３−クロ
ロ−５−トリフルオロメチルピリジンが９０％生成して
いた。反応終了後冷却し実施例９の場合と同様の後処理
を行なったところ、１６．０ｇの２−アミノ−３−クロ
ロ−５−トリフルオロメチルピリジン（液体クロマトグ
ラフィーによる純度９７％、収率７９％）が得られた。Example 10 In a 300 ml four-necked flask as in Example 1, 16.2 g of 2-amino-5-trifluoromethylpyridine (0.
1 mol) and 150 g of toluene, and then cooled to 0 to 5 ° C., and stirred while stirring to obtain 10.1 g of trichloroisocyanuric acid.
(0.043 mol) was added in portions over 1 hour.
After the addition, the reaction was carried out by stirring at the same temperature for 3 hours. When the reaction product was analyzed using liquid chromatography,
91% of 2-chloroamino-5-trifluoromethylpyridine and 6% of 2-amino-3-chloro-5-trifluoromethylpyridine were produced. Thereafter, the reactants were
The mixture was heated to 0 ° C., and a rearrangement reaction was performed for 2 hours while stirring. When the reaction product was analyzed using liquid chromatography, the peak of 2-chloroamino-5-trifluoromethylpyridine disappeared, and 90% of 2-amino-3-chloro-5-trifluoromethylpyridine was produced. Was. After completion of the reaction, the reaction mixture was cooled and subjected to the same post-treatment as in Example 9. As a result, 16.0 g of 2-amino-3-chloro-5-trifluoromethylpyridine (purity 97% by liquid chromatography, yield 79) %)was gotten.
【００６５】実施例１１ 実施例１と同様の３００ml四つ口フラスコに、２−アミ
ノ−５−ニトロピリジン１３．９ｇ（０．１モル）、Ｎ
−クロロコハク酸イミド１５．４ｇ（０．１１５モル）
およびトルエン１５０ｇを加え、８０℃で１時間加熱、
攪拌して反応を行なった。反応途中に２−クロロアミノ
−５−ニトロピリジンの生成が確認された。反応終了
後、室温まで冷却し、水１００ｇを加えて攪拌した。水
層とオイル層を分液し、オイル層のトルエンを減圧下で
留去したところ、２−アミノ−３−クロロ−５−ニトロ
ピリジン９１％、原料の２−アミノ−５−ニトロピリジ
ン０．７％を含む黄色結晶１８．０ｇ（２−アミノ−３
−クロロ−５−ニトロピリジンの収率９４．４％）が得
られた。Example 11 In a 300 ml four-necked flask as in Example 1, 13.9 g (0.1 mol) of 2-amino-5-nitropyridine and N
-15.4 g (0.115 mol) of chlorosuccinimide
And 150 g of toluene, and heated at 80 ° C. for 1 hour,
The reaction was performed with stirring. Generation of 2-chloroamino-5-nitropyridine was confirmed during the reaction. After completion of the reaction, the mixture was cooled to room temperature, 100 g of water was added, and the mixture was stirred. The aqueous layer and the oil layer were separated, and the toluene in the oil layer was distilled off under reduced pressure. As a result, 91% of 2-amino-3-chloro-5-nitropyridine and 0.2% of raw material 2-amino-5-nitropyridine were added. 18.0 g of yellow crystals containing 7% (2-amino-3
-Chloro-5-nitropyridine yield: 94.4%).
【００６６】実施例１２ 攪拌機、温度計、滴下ロートおよび還流冷却管の付した
３００ｍｌ四つ口フラスコに、実施例１の工程（１）に
準じて調製された２−アミノ−５−トリフルオロメチル
ピリジン１６．２ｇ（０．１モル）およびトルエン７５
ｇを加え、０〜５℃に冷却した。次にｔｅｒｔ−ブチル
ハイポクロライド１２．５ｇ（０．１１５モル）および
トルエン７５ｇの混合溶液を同温度で１時間にわたって
滴下ロートから滴下した。滴下後、同温度で３０分攪拌
して反応をおこなった。反応物を液体クロマトグラフィ
ーを用いて分析したところ、２−クロロアミノ−５−ト
リフルオロメチルピリジンが９５％、２−アミノ−３−
クロロ−５−トリフルオロメチルピリジンが１％生成し
ていた。Example 12 A 300 ml four-necked flask equipped with a stirrer, a thermometer, a dropping funnel and a reflux condenser was charged with 2-amino-5-trifluoromethyl prepared according to the step (1) of Example 1. 16.2 g (0.1 mol) of pyridine and 75 of toluene
g was added and cooled to 0-5 ° C. Next, a mixed solution of 12.5 g (0.115 mol) of tert-butyl hypochloride and 75 g of toluene was dropped from the dropping funnel at the same temperature for 1 hour. After the addition, the mixture was stirred at the same temperature for 30 minutes to carry out a reaction. The reaction product was analyzed using liquid chromatography to find that 95% of 2-chloroamino-5-trifluoromethylpyridine was 2-amino-3-
1% of chloro-5-trifluoromethylpyridine was produced.
【００６７】その後、反応物中に酢酸０．３ｇを加え、
７０℃に加熱し、攪拌しながら転位反応を１時間おこな
った。反応物を液体クロマトグラフィーを用いて分析し
たところ、２−クロロアミノ−５−トリフルオロメチル
ピリジンのピークは消失しており、２−アミノ−３−ク
ロロ−５−トリフルオロメチルピリジンが８９％生成し
ていた。反応終了後、室温まで冷却し、２０％塩酸水溶
液を加えて攪拌した。水層とオイル層を分液し、水層を
２５％水酸化ナトリウム水溶液を用い中和した。析出し
た微黄色結晶を濾過し、乾燥したところ、１７．３ｇの
２−アミノ−３−クロロ−５−トリフルオロメチルピリ
ジン（液体クロマトグラフィーによる純度９８％、収率
８６％）が得られた。Thereafter, 0.3 g of acetic acid was added to the reaction product,
The mixture was heated to 70 ° C., and a rearrangement reaction was performed for 1 hour while stirring. When the reaction product was analyzed by liquid chromatography, the peak of 2-chloroamino-5-trifluoromethylpyridine disappeared, and 89% of 2-amino-3-chloro-5-trifluoromethylpyridine was produced. Was. After the completion of the reaction, the mixture was cooled to room temperature, a 20% aqueous hydrochloric acid solution was added, and the mixture was stirred. The aqueous layer and the oil layer were separated, and the aqueous layer was neutralized using a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried to obtain 17.3 g of 2-amino-3-chloro-5-trifluoromethylpyridine (purity 98% by liquid chromatography, yield 86%).
【００６８】実施例１３ 攪拌機、温度計、ガス吹込み管および還流冷却管の付し
た３００ｍｌ四つ口フラスコに、実施例１の工程（１）
に準じて調製された２−アミノ−５−トリフルオロメチ
ルピリジン３２．４ｇ（０．２モル）およびトルエン１
５０ｇを加え、０〜５℃で冷却し、攪拌しながら塩素
７．１ｇ（０．１モル）を３０分にわたって吹込んだ。
吹込みと同時に、２−アミノ−５−トリフルオロメチル
ピリジンの塩酸塩が析出した。反応物を液体クロマトグ
ラフィーを用いて分析したところ、２−クロロアミノ−
５−トリフルオロメチルピリジンが４８％、２−アミノ
−５−トリフルオロメチルピリジンの塩酸塩が４９％生
成していた。Example 13 Step (1) of Example 1 was carried out in a 300 ml four-necked flask equipped with a stirrer, a thermometer, a gas injection pipe and a reflux condenser.
32.4 g (0.2 mol) of 2-amino-5-trifluoromethylpyridine and toluene 1 prepared according to
50 g was added, the mixture was cooled at 0 to 5 ° C., and 7.1 g (0.1 mol) of chlorine was blown in with stirring over 30 minutes.
Simultaneously with the blowing, the hydrochloride of 2-amino-5-trifluoromethylpyridine precipitated. When the reaction product was analyzed using liquid chromatography, 2-chloroamino-
48% of 5-trifluoromethylpyridine and 49% of hydrochloride of 2-amino-5-trifluoromethylpyridine were produced.
【００６９】その後、反応物中に酢酸１ｇを加え８０℃
に加熱し、攪拌しながら転位反応を３０分おこなった。
反応物を液体クロマトグラフィーを用いて分析したとこ
ろ、２−クロロアミノ−５−トリフルオロメチルピリジ
ンのピークは消失しており、２−アミノ−３−クロロ−
５−トリフルオロメチルピリジンが４５％、２−アミノ
−５−トリフルオロメチルピリジンの塩酸塩が４８％生
成していた。反応終了後冷却し、反応で生成し析出した
２−アミノ−５−トリフルオロメチルピリジンの塩酸塩
を濾過した。オイル層に２０％塩酸水溶液を加えて攪拌
し、さらに水層とオイル層を分液し、水層を２５％水酸
化ナトリウム水溶液を用い中和した。析出した微黄色結
晶を濾過し、乾燥したところ、１６．７ｇの２−アミノ
−３−クロロ−５−トリフルオロメチルピリジン（液体
クロマトグラフィーによる純度９７％、収率４１．２
％）が得られた。Thereafter, 1 g of acetic acid was added to the reaction product, and 80 ° C.
, And a rearrangement reaction was carried out for 30 minutes with stirring.
When the reaction product was analyzed using liquid chromatography, the peak of 2-chloroamino-5-trifluoromethylpyridine disappeared, and 2-amino-3-chloro-
45% of 5-trifluoromethylpyridine and 48% of hydrochloride of 2-amino-5-trifluoromethylpyridine were produced. After completion of the reaction, the mixture was cooled, and the hydrochloride of 2-amino-5-trifluoromethylpyridine generated and precipitated by the reaction was filtered. A 20% aqueous hydrochloric acid solution was added to the oil layer and the mixture was stirred. The aqueous layer and the oil layer were separated, and the aqueous layer was neutralized with a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried, and 16.7 g of 2-amino-3-chloro-5-trifluoromethylpyridine (purity 97% by liquid chromatography, yield 41.2 g) was obtained.
%)was gotten.
【００７０】また先に濾過して得られた２−アミノ−５
−トリフルオロメチルピリジンの塩酸塩は乾燥したとこ
ろ１８．９ｇ（収率４７．６％）であった。この塩酸塩
を水に溶解し中和後、トルエンで抽出することにより次
の反応の原料としてリサイクル使用することができる。
なお、この反応でのオイル収率は２−アミノ−５−トリ
フルオロメチルピリジンの塩酸塩４７．６％、２−アミ
ノ−３−クロロ−５−トリフルオロメチルピリジン４
１．２％であり、トータル収率として８８．８％とな
る。The 2-amino-5 obtained by filtration
18.9 g (yield 47.6%) of the hydrochloride of -trifluoromethylpyridine was dried. This hydrochloride is dissolved in water, neutralized, and extracted with toluene, so that it can be recycled as a raw material for the next reaction.
The oil yield in this reaction was 47.6% for 2-amino-5-trifluoromethylpyridine hydrochloride, and 2-amino-3-chloro-5-trifluoromethylpyridine 4
1.2%, giving a total yield of 88.8%.
【００７１】実施例１４ 攪拌機、温度計、ガス吹込み管および還流冷却管の付し
た３００ml四つ口フラスコに２−アミノ−３−クロロ−
５−トリフルオロメチルピリジン３９．３ｇ（０．２モ
ル）およびトルエン１５０ｇを加え０〜５℃に冷却し攪
拌しながら塩素ガス７．１ｇ（０．１モル）を３０分に
わたって吹込んだ。吹込みと同時に、２−アミノ−３−
クロロ−５−トリフルオロメチルピリジンの塩素塩が析
出した。反応物を液体クロマトグラフィーを用いて分析
したところ、２−クロロアミノ−３−クロロ−５−トリ
フルオロメチルピリジンが４９％、２−アミノ−３−ク
ロロ−５−トリフルオロメチルピリジンの塩酸塩が４９
％生成していた。Example 14 A 300 ml four-necked flask equipped with a stirrer, thermometer, gas injection tube and reflux condenser was charged with 2-amino-3-chloro-.
39.3 g (0.2 mol) of 5-trifluoromethylpyridine and 150 g of toluene were added, and the mixture was cooled to 0 to 5 ° C., and 7.1 g (0.1 mol) of chlorine gas was blown in over 30 minutes while stirring. 2-amino-3-
Chlorine-5-trifluoromethylpyridine chloride salt precipitated. When the reaction product was analyzed using liquid chromatography, 49% of 2-chloroamino-3-chloro-5-trifluoromethylpyridine and hydrochloride of 2-amino-3-chloro-5-trifluoromethylpyridine were obtained. 49
% Had been generated.
【００７２】その後、反応物中に２−アミノ−５−トリ
フルオロメチルピリジン１６．２ｇ（０．１モル）を加
え、２０℃に加熱し同温度で２時間攪拌した。反応物を
液体クロマトグラフィーで分析したところ、２−クロロ
アミノ−３−クロロ−５−トリフルオロメチルピリジン
は１％に減少し、あらたに２−クロロアミノ−５−トリ
フルオロメチルピリジンが３１％、２−アミノ−３−ク
ロロ−５−トリフルオロメチルピリジンが３０％生成し
ていた。残りは、２−アミノ−３−クロロ−５−トリフ
ルオロメチルピリジンの塩酸塩であった。Thereafter, 16.2 g (0.1 mol) of 2-amino-5-trifluoromethylpyridine was added to the reaction product, heated to 20 ° C., and stirred at the same temperature for 2 hours. When the reaction product was analyzed by liquid chromatography, 2-chloroamino-3-chloro-5-trifluoromethylpyridine was reduced to 1%, and 2-chloroamino-5-trifluoromethylpyridine was newly added to 31%. 30% of 2-amino-3-chloro-5-trifluoromethylpyridine was produced. The balance was 2-amino-3-chloro-5-trifluoromethylpyridine hydrochloride.
【００７３】さらに、反応物中に酢酸１ｇを加え８０℃
に加熱し、攪拌しながら転位反応を３０分間おこなっ
た。反応物を液体クロマトグラフィーを用い分析したと
ころ、２−クロロアミノ−５−トリフルオロメチルピリ
ジンのピークは消失しており、２−アミノ−３−クロロ
−５−トリフルオロメチルピリジンが６３％、２−アミ
ノ−３−クロロ−５−トリフルオロメチルピリジンの塩
酸塩が３２％生成していた。反応終了後冷却し、反応物
中に２０％塩酸水溶液を加えて攪拌し、さらに水層とオ
イル層を分液し、水層を２５％水酸化ナトリウム水溶液
を用い中和した。析出した微黄色結晶を濾過し、乾燥し
たところ５５．９ｇの２−アミノ−３−クロロ−５−ト
リフルオロメチルピリジン（液体クロマトグラフィーに
よる純度９８％、収率９２．９％）が得られた。Further, 1 g of acetic acid was added to the reaction product, and 80 ° C.
And the rearrangement reaction was carried out for 30 minutes while stirring. When the reaction product was analyzed using liquid chromatography, the peak of 2-chloroamino-5-trifluoromethylpyridine disappeared, and the content of 2-amino-3-chloro-5-trifluoromethylpyridine was 63%, -Amino-3-chloro-5-trifluoromethylpyridine hydrochloride was 32% produced. After completion of the reaction, the reaction mixture was cooled, a 20% aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was stirred. The aqueous layer and the oil layer were separated, and the aqueous layer was neutralized with a 25% aqueous sodium hydroxide solution. The precipitated pale yellow crystals were filtered and dried to obtain 55.9 g of 2-amino-3-chloro-5-trifluoromethylpyridine (purity by liquid chromatography: 98%, yield: 92.9%). .
【００７４】実施例１５ 攪拌機、温度計および還流冷却管の付した５００ml四つ
口フラスコに２−アミノ−５−シアノピリジン６．０ｇ
（０．０５モル）、Ｎ−クロロコハク酸イミド８．３ｇ
（０．０６２５モル）およびアセトニトリル２００ｇを
加え５０℃で１時間攪拌して反応を行った。反応途中で
反応物を液体クロマトグラフィーを用い分析したとこ
ろ、２−クロロアミノ−５−シアノピリジンの生成を確
認した。反応終了後、アセトニトリルを留去した。コハ
ク酸イミドと目的とする生成物とを分離するため、残っ
た反応物中に水５０ｇを入れ攪拌した。析出した結晶を
濾過し、さらにトルエン５０ｇでこの結晶を洗浄し乾燥
したところ、淡褐色結晶の２−アミノ−３−クロロ−５
−シアノピリジン６．９ｇ（液体クロマトグラフィーに
よる純度９８％、収率８８％）が得られた。なお、この
ものの融点は１９３．９〜１９４．０℃（未補正）であ
り、また質量分析結果はＭ+ ：１５３、Ｍ+ −Cl：１１
８Example 15 6.0 g of 2-amino-5-cyanopyridine was placed in a 500 ml four-necked flask equipped with a stirrer, thermometer and reflux condenser.
(0.05 mol), 8.3 g of N-chlorosuccinimide
(0.0625 mol) and 200 g of acetonitrile were added and stirred at 50 ° C. for 1 hour to carry out a reaction. The reaction product was analyzed using liquid chromatography during the reaction, and the formation of 2-chloroamino-5-cyanopyridine was confirmed. After completion of the reaction, acetonitrile was distilled off. In order to separate the succinimide from the desired product, 50 g of water was added to the remaining reactant and stirred. The precipitated crystals were collected by filtration, washed with 50 g of toluene, and dried to obtain 2-amino-3-chloro-5 as light brown crystals.
-6.9 g of cyanopyridine (purity 98% by liquid chromatography, yield 88%) was obtained. The melting point of this product was 193.9 to 194.0 ° C. (uncorrected), and the mass spectrometry results were M + : 153, M + -Cl: 11.
8
【００７５】[0075]
【発明の効果】本発明によれば一般式（Ｉ）の芳香族化
合物から簡単な反応操作、反応工程により、一般式（I
I）の３−ハロゲノ芳香族化合物を、余り副反応を伴な
わずに良好に生成することができるので、本発明方法は
工業的に適用しうる。According to the present invention, the aromatic compound represented by the general formula (I) is prepared from the aromatic compound represented by the general formula (I) by a simple reaction operation and reaction steps.
Since the 3-halogeno aromatic compound of I) can be produced satisfactorily without much side reaction, the method of the present invention is industrially applicable.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ Ｃ０７Ｃ 209/54 Ｃ０７Ｃ 209/54 211/52 211/52 239/04 239/04 239/06 239/06 255/53 255/53 255/58 255/58 Ｃ０７Ｄ 213/64 Ｃ０７Ｄ 213/64 213/75 213/75 213/84 213/84 Ｚ // Ｃ０７Ｂ 61/00 ３００ Ｃ０７Ｂ 61/00 ３００ (31)優先権主張番号 特願平4−362020 (32)優先日 平成４年12月26日(1992．12．26) (33)優先権主張国 日本（ＪＰ） (31)優先権主張番号 特願平5−65874 (32)優先日 平成５年２月15日(1993．2．15) (33)優先権主張国 日本（ＪＰ） (58)調査した分野(Int.Cl.7，ＤＢ名) C07D 213/00 - 213/90 C07B 1/00 - 61/00 C07C 37/00 - 37/62 C07C 39/00 - 39/26 C07C 205/00 - 205/11 C07C 209/00 - 209/54 C07C 211/52 C07C 239/00 - 239/06 C07C 255/00 - 255/58 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on front page (51) Int.Cl. 7 Identification code FI C07C 209/54 C07C 209/54 211/52 211/52 239/04 239/04 239/06 239/06 255/53 255/53 255/58 255/58 C07D 213/64 C07D 213/64 213/75 213/75 213/84 213/84 Z // C07B 61/00 300 C07B 61/00 300 (31) Priority claim number Japanese Patent Application No. 4 -362020 (32) Priority date December 26, 1992 (1992.1.26) (33) Priority claiming country Japan (JP) (31) Priority claim number Japanese Patent Application No. 5-65874 (32) Priority date February 15, 1993 (Feb. 15, 1993) (33) Countries claiming priority Japan (JP) (58) Fields investigated (Int. Cl. 7 , DB name) C07D 213/00-213/90 C07B 1/00-61/00 C07C 37/00-37/62 C07C 39/00-39/26 C07C 205/00-205/11 C07C 209/00-209/54 C07C 211/52 C07C 239/00-239 / 06 C07C 255/00-255/58 CA (STN) REGI STRY (STN)
Claims (10)
り、Ｚ1およびＺ2は水素原子またはハロゲン原子であ
り、ＲおよびＹは一方が水素原子、他方がニトロ基、シ
アノ基またはトリフルオロメチル基であり、Ｑは窒素原
子または−Ｃ（Ｔ）＝基（Ｔは水素原子、ハロゲン原
子、ニトロ基、シアノ基またはトリフルオロメチル基）
である〕で表される芳香族化合物とハロゲン化剤とを反
応させて一般式（ＩＩ） 【化２】 （式中Ｒ′およびＹ′は一方がハロゲン原子、他方がニ
トロ基、シアノ基またはトリフルオロメチル基であり、
Ｘ、Ｚ1、Ｚ2およびＱは前述のとおりである）で表され
る３−ハロゲノ芳香族化合物を製造する方法において、
前記芳香族化合物とハロゲン化剤とを反応させて一般式
（ＩＩＩ） 【化３】 〔式中Ｅは 【化４】 （Ａは水素原子またはアシル基であり、Ｈａｌはハロゲ
ン原子）であり、Ｚ1、Ｚ2、Ｒ、ＹおよびＱは前述のと
おりである〕で表されるハロゲノ芳香族化合物を生成さ
せ、このハロゲノ芳香族化合物をプロトン供与体の存在
下に転位反応させて前記３−ハロゲノ芳香族化合物を生
成させることを特徴とする芳香族化合物のハロゲン化方
法。1. A compound of the general formula (I) Wherein X is a hydroxyl group, an amino group or an acylamino group, Z 1 and Z 2 are a hydrogen atom or a halogen atom, and R and Y are one of a hydrogen atom and the other is a nitro, cyano or trifluoromethyl group. And Q is a nitrogen atom or -C (T) = group (T is a hydrogen atom, a halogen atom, a nitro group, a cyano group or a trifluoromethyl group)
Is reacted with a halogenating agent to produce a compound represented by the general formula (II): Wherein one of R ′ and Y ′ is a halogen atom and the other is a nitro, cyano or trifluoromethyl group;
X, Z 1 , Z 2 and Q are as defined above) in the method for producing a 3-halogeno aromatic compound represented by the formula:
The aromatic compound is reacted with a halogenating agent to form a compound represented by the general formula (III): [E in the formula is (A is a hydrogen atom or an acyl group, Hal is a halogen atom), and Z 1 , Z 2 , R, Y and Q are as described above). A method for halogenating an aromatic compound, comprising subjecting a halogeno aromatic compound to a rearrangement reaction in the presence of a proton donor to produce the 3-halogeno aromatic compound.
り、Ｚ1およびＺ2は水素原子またはハロゲン原子であ
り、ＲおよびＹは一方が水素原子、他方がニトロ基、シ
アノ基またはトリフルオロメチル基である）で表される
ピリジン類とハロゲン化剤とを反応させて一般式（Ｉ
Ｉ′） 【化６】 （式中Ｒ′およびＹ′は一方がハロゲン原子、他方がニ
トロ基、シアノ基またはトリフルオロメチル基であり、
Ｘ、Ｚ1およびＺ2は前述のとおりである）で表される３
−ハロゲノピリジン類を製造する方法において、前記ピ
リジン類とハロゲン化剤とを反応させて一般式（ＩＩ
Ｉ′） 【化７】 〔式中Ｅは 【化８】 （Ａは水素原子またはアシル基であり、Ｈａｌはハロゲ
ン原子）であり、Ｚ1、Ｚ2、ＲおよびＹは前述のとおり
である〕で表されるハロゲノピリジン類を生成させ、こ
のハロゲノピリジン類をプロトン供与体の存在下に転位
反応させて前記３−ハロゲノピリジン類を生成させるこ
とを特徴とするピリジン類のハロゲン化方法。2. A compound of the general formula (I ') Wherein X is a hydroxyl group, an amino group or an acylamino group, Z 1 and Z 2 are a hydrogen atom or a halogen atom, and R and Y are one of a hydrogen atom and the other is a nitro, cyano or trifluoromethyl group. Is reacted with a halogenating agent to give a compound of the general formula (I
I ') Wherein one of R ′ and Y ′ is a halogen atom and the other is a nitro, cyano or trifluoromethyl group;
X, Z 1 and Z 2 are as described above)
In the method for producing halogenopyridines, the pyridines are reacted with a halogenating agent to obtain a compound represented by the general formula (II)
I ') [E in the formula is (A is a hydrogen atom or an acyl group, Hal is a halogen atom), and Z 1 , Z 2 , R and Y are the same as described above). Wherein the compound is subjected to a rearrangement reaction in the presence of a proton donor to produce the 3-halogenopyridines.
酸イミド、Ｎ−ハロゲノフタル酸イミド、ｔｅｒｔ−ブ
チルハイポハライド、塩素ガス、臭素、トリハロゲノイ
ソシアヌル酸、ジハロゲノイソシアヌル酸あるいはそれ
らの塩または一般式（ＩＶ） 【化９】 （Ｒ′、Ｙ′、Ｅ、Ｚ1およびＺ2は前述のとおりであ
る）で表されるハロゲノ３−ハロゲノピリジン類であ
り、プロトン供与体がカルボン酸類、コハク酸イミド、
フタル酸イミドまたはイソシアヌル酸である請求項１又
は２の方法。3. The method according to claim 1, wherein the halogenating agent is N-halogenosuccinimide, N-halogenophthalimide, tert-butyl hypohalide, chlorine gas, bromine, trihalogeno isocyanuric acid, dihalogeno isocyanuric acid, or a salt thereof or a salt thereof. Formula (IV) Wherein R ′, Y ′, E, Z 1 and Z 2 are as described above, wherein the proton donor is a carboxylic acid, succinimide,
3. The method according to claim 1, which is phthalimide or isocyanuric acid.
ロゲノピリジン類、塩素ガスまたは臭素であり、前記プ
ロトン供与体が蟻酸、酢酸およびプロピオン酸からなる
群から選ばれた少くとも一種のカルボン酸である請求項
１又は２の方法。4. The halogenating agent is the halogeno-3-halogenopyridines, chlorine gas or bromine, and the proton donor is at least one carboxylic acid selected from the group consisting of formic acid, acetic acid and propionic acid. 3. The method of claim 1 or claim 2.
媒の還流温度でおこない、前記転位反応を０℃ないし溶
媒の還流温度でおこなう請求項１又は２の方法。5. The method according to claim 1, wherein the halogenation reaction is carried out at -20 ° C. to the reflux temperature of the solvent, and the rearrangement reaction is carried out at 0 ° C. to the reflux temperature of the solvent.
ン化してハロゲノ３−ハロゲノ芳香族化合物を生成さ
せ、前記一般式（Ｉ）で表される芳香族化合物を、前記
ハロゲノ３−ハロゲノ芳香族化合物を用いてハロゲン化
してハロゲノ芳香族化合物を生成させ、このハロゲノ芳
香族化合物を転位反応させて３−ハロゲノ芳香族化合物
を製造する請求項１又は２の方法。6. A halogenated 3-halogeno aromatic compound to produce a halogeno 3-halogeno aromatic compound, and the aromatic compound represented by the general formula (I) is converted to the halogeno 3-halogeno aromatic compound. The method according to claim 1 or 2, wherein halogenation is carried out to produce a halogeno aromatic compound, and the halogeno aromatic compound is subjected to a rearrangement reaction to produce a 3-halogeno aromatic compound.
化してハロゲノ３−ハロゲノピリジン類を生成させ、前
記一般式（Ｉ′）で表されるピリジン類を、前記ハロゲ
ノ３−ハロゲノピリジン類を用いてハロゲン化してハロ
ゲノピリジン類を生成させ、このハロゲノピリジン類を
転位反応させて３−ハロゲノピリジン類を製造する請求
項２、３、４または５の方法。7. The halogenation of the 3-halogenopyridines to generate halogeno-3-halogenopyridines, and the pyridines represented by the general formula (I ′) are converted using the halogeno-3-halogenopyridines. The method according to claim 2, 3, 4 or 5, wherein halogenation is carried out to produce halogenopyridines, and the halogenopyridines are rearranged to produce 3-halogenopyridines.
リジン、２−アミノ−５−ニトロピリジンまたは２−ア
ミノ−５−シアノピリジンと塩素ガスとを反応させて２
−クロロアミノ−５−トリフルオロメチルピリジン、２
−クロロアミノ−５−ニトロピリジンまたは２−クロロ
アミノ−５−シアノピリジンを生成させ、このものを蟻
酸、酢酸およびプロピオン酸からなる群から選ばれた少
くとも一種のカルボン酸の存在下に転位反応させて２−
アミノ−３−クロロ−５−トリフルオロメチルピリジ
ン、２−アミノ−３−クロロ−５−ニトロピリジンまた
は２−アミノ−３−クロロ−５−シアノピリジンを製造
する請求項２、３、４、５または７の方法。8. The reaction of 2-amino-5-trifluoromethylpyridine, 2-amino-5-nitropyridine or 2-amino-5-cyanopyridine with chlorine gas to obtain
-Chloroamino-5-trifluoromethylpyridine, 2
-Chloroamino-5-nitropyridine or 2-chloroamino-5-cyanopyridine, which is rearranged in the presence of at least one carboxylic acid selected from the group consisting of formic acid, acetic acid and propionic acid Let me 2-
A process for producing amino-3-chloro-5-trifluoromethylpyridine, 2-amino-3-chloro-5-nitropyridine or 2-amino-3-chloro-5-cyanopyridine. Or the method of 7.
リジンと塩素ガスとを反応させて２−クロロアミノ−５
−トリフルオロメチルピリジンを生成させ、このものを
蟻酸、酢酸およびプロピオン酸からなる群から選ばれた
少くとも一種のカルボン酸の存在下に転位反応させて２
−アミノ−３−クロロ−５−トリフルオロメチルピリジ
ンを製造する請求項２、３、４、５または７の方法。9. The reaction of 2-amino-5-trifluoromethylpyridine with chlorine gas to form 2-chloroamino-5
To form a trifluoromethylpyridine, which is rearranged in the presence of at least one carboxylic acid selected from the group consisting of formic acid, acetic acid and propionic acid to give 2
8. The method of claim 2, 3, 4, 5 or 7 for producing -amino-3-chloro-5-trifluoromethylpyridine.
℃でおこない、前記転位反応を０℃ないし溶媒の還流温
度でおこなう請求項２、３、４、７、８または９の方
法。10. The chlorination reaction is carried out at -20.degree.
The method according to claim 2, wherein the rearrangement reaction is carried out at 0 ° C. to the reflux temperature of the solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28746893A JP3311840B2 (en) | 1992-11-04 | 1993-10-22 | Method for halogenating aromatic compounds |
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33653792 | 1992-11-04 | ||
| JP35227392 | 1992-11-20 | ||
| JP35809392 | 1992-12-07 | ||
| JP36202092 | 1992-12-26 | ||
| JP4-358093 | 1993-02-15 | ||
| JP4-362020 | 1993-02-15 | ||
| JP4-336537 | 1993-02-15 | ||
| JP5-65874 | 1993-02-15 | ||
| JP6587493 | 1993-02-15 | ||
| JP4-352273 | 1993-02-15 | ||
| JP28746893A JP3311840B2 (en) | 1992-11-04 | 1993-10-22 | Method for halogenating aromatic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06293737A JPH06293737A (en) | 1994-10-21 |
| JP3311840B2 true JP3311840B2 (en) | 2002-08-05 |
Family
ID=27551022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28746893A Expired - Lifetime JP3311840B2 (en) | 1992-11-04 | 1993-10-22 | Method for halogenating aromatic compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3311840B2 (en) |
-
1993
- 1993-10-22 JP JP28746893A patent/JP3311840B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06293737A (en) | 1994-10-21 |
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