EP3931184A1 - Method for producing quinoxalines - Google Patents
Method for producing quinoxalinesInfo
- Publication number
- EP3931184A1 EP3931184A1 EP20712212.8A EP20712212A EP3931184A1 EP 3931184 A1 EP3931184 A1 EP 3931184A1 EP 20712212 A EP20712212 A EP 20712212A EP 3931184 A1 EP3931184 A1 EP 3931184A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- reaction
- solvent
- phenylenediamine
- reaction temperature
- acetic acid
- 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.)
- Pending
Links
- 150000003252 quinoxalines Chemical class 0.000 title claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 title abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 25
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000009833 condensation Methods 0.000 claims abstract description 10
- 230000005494 condensation Effects 0.000 claims abstract description 10
- 150000004987 o-phenylenediamines Chemical class 0.000 claims abstract description 10
- 238000006482 condensation reaction Methods 0.000 claims abstract description 9
- 238000010438 heat treatment Methods 0.000 claims abstract description 8
- 125000005594 diketone group Chemical group 0.000 claims abstract description 7
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000004429 atom Chemical group 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 22
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 4
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical group C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- -1 2,3-bis (4-methoxyphenyl) quinoxalin-6-yl Chemical group 0.000 claims 1
- GCHSAWQUXLOIJS-UHFFFAOYSA-N 2-(4-methoxyphenyl)quinoxaline Chemical compound C1=CC(OC)=CC=C1C1=CN=C(C=CC=C2)C2=N1 GCHSAWQUXLOIJS-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 229960000583 acetic acid Drugs 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 230000035484 reaction time Effects 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 229960004756 ethanol Drugs 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- KHPYJVQRBJJYSF-UHFFFAOYSA-N phenanthro[9,10-b]quinoxaline Chemical compound C1=CC=C2C3=NC4=CC=CC=C4N=C3C3=CC=CC=C3C2=C1 KHPYJVQRBJJYSF-UHFFFAOYSA-N 0.000 description 4
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VMAUSAPAESMXAB-UHFFFAOYSA-N 2,3-bis(4-fluorophenyl)quinoxaline Chemical compound C1=CC(F)=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=C(F)C=C1 VMAUSAPAESMXAB-UHFFFAOYSA-N 0.000 description 3
- JMLIBSAYWRQXIV-UHFFFAOYSA-N 2,3-bis(4-methoxyphenyl)quinoxaline Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=C(OC)C=C1 JMLIBSAYWRQXIV-UHFFFAOYSA-N 0.000 description 3
- RSNQVABHABAKEZ-UHFFFAOYSA-N 2,3-diphenylquinoxaline Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=CC=C1 RSNQVABHABAKEZ-UHFFFAOYSA-N 0.000 description 3
- FCGFZVAKWAIWSE-UHFFFAOYSA-N 2,3-diphenylquinoxaline-6-carbonitrile Chemical compound C=1C=CC=CC=1C1=NC2=CC(C#N)=CC=C2N=C1C1=CC=CC=C1 FCGFZVAKWAIWSE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- SHGCOCRWIDCDMO-UHFFFAOYSA-N (2,3-diphenylquinoxalin-6-yl)-phenylmethanone Chemical compound C=1C=C2N=C(C=3C=CC=CC=3)C(C=3C=CC=CC=3)=NC2=CC=1C(=O)C1=CC=CC=C1 SHGCOCRWIDCDMO-UHFFFAOYSA-N 0.000 description 2
- PIINXYKJQGMIOZ-UHFFFAOYSA-N 1,2-dipyridin-2-ylethane-1,2-dione Chemical compound C=1C=CC=NC=1C(=O)C(=O)C1=CC=CC=N1 PIINXYKJQGMIOZ-UHFFFAOYSA-N 0.000 description 2
- WJKWZEQHHHGYTH-UHFFFAOYSA-N 1-(2,3-dimethoxyphenyl)-2-phenylethane-1,2-dione Chemical compound COC1=CC=CC(C(=O)C(=O)C=2C=CC=CC=2)=C1OC WJKWZEQHHHGYTH-UHFFFAOYSA-N 0.000 description 2
- GMUROSQCXMKHEN-UHFFFAOYSA-N 2,3-bis(furan-2-yl)quinoxaline Chemical compound C1=COC(C=2C(=NC3=CC=CC=C3N=2)C=2OC=CC=2)=C1 GMUROSQCXMKHEN-UHFFFAOYSA-N 0.000 description 2
- VVWXQXJKRHESNM-UHFFFAOYSA-N 6-[2,3-bis(4-methoxyphenyl)quinoxalin-6-yl]-2,3-bis(4-methoxyphenyl)quinoxaline Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=C(C=3C=C4N=C(C(C=5C=CC(OC)=CC=5)=NC4=CC=3)C=3C=CC(OC)=CC=3)C=C2N=C1C1=CC=C(OC)C=C1 VVWXQXJKRHESNM-UHFFFAOYSA-N 0.000 description 2
- XLVXYKCXPXIGEB-UHFFFAOYSA-N 6-methyl-2,3-diphenylquinoxaline Chemical compound C=1C=CC=CC=1C1=NC2=CC(C)=CC=C2N=C1C1=CC=CC=C1 XLVXYKCXPXIGEB-UHFFFAOYSA-N 0.000 description 2
- QSJFEWWENJXUCR-UHFFFAOYSA-N 6-nitro-2,3-diphenylquinoxaline Chemical compound C=1C=CC=CC=1C1=NC2=CC([N+](=O)[O-])=CC=C2N=C1C1=CC=CC=C1 QSJFEWWENJXUCR-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- CUWGAAPCPYDMPT-UHFFFAOYSA-N methyl 2,3-diphenylquinoxaline-6-carboxylate Chemical compound C=1C=CC=CC=1C1=NC2=CC(C(=O)OC)=CC=C2N=C1C1=CC=CC=C1 CUWGAAPCPYDMPT-UHFFFAOYSA-N 0.000 description 2
- 230000005693 optoelectronics Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- VZPGINJWPPHRLS-UHFFFAOYSA-N phenazine-2,3-diamine Chemical compound C1=CC=C2N=C(C=C(C(N)=C3)N)C3=NC2=C1 VZPGINJWPPHRLS-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- BRKULQOUSCHDGS-UHFFFAOYSA-N 1,2-bis(4-fluorophenyl)ethane-1,2-dione Chemical compound C1=CC(F)=CC=C1C(=O)C(=O)C1=CC=C(F)C=C1 BRKULQOUSCHDGS-UHFFFAOYSA-N 0.000 description 1
- YNANGXWUZWWFKX-UHFFFAOYSA-N 1,2-bis(4-methoxyphenyl)ethane-1,2-dione Chemical compound C1=CC(OC)=CC=C1C(=O)C(=O)C1=CC=C(OC)C=C1 YNANGXWUZWWFKX-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- BVQVLAIMHVDZEL-UHFFFAOYSA-N 1-phenyl-1,2-propanedione Chemical compound CC(=O)C(=O)C1=CC=CC=C1 BVQVLAIMHVDZEL-UHFFFAOYSA-N 0.000 description 1
- ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical compound N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 1
- ZFWBPJPGICYCIV-UHFFFAOYSA-N 2,3-dithiophen-2-ylquinoxaline Chemical compound C1=CSC(C=2C(=NC3=CC=CC=C3N=2)C=2SC=CC=2)=C1 ZFWBPJPGICYCIV-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- QWNCDHYYJATYOG-UHFFFAOYSA-N 2-phenylquinoxaline Chemical compound C1=CC=CC=C1C1=CN=C(C=CC=C2)C2=N1 QWNCDHYYJATYOG-UHFFFAOYSA-N 0.000 description 1
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 description 1
- QESBRXIXJOBVGC-UHFFFAOYSA-N 6-(2,3-diphenylquinoxalin-6-yl)-2,3-diphenylquinoxaline Chemical compound C1=CC=CC=C1C1=NC2=CC=C(C=3C=C4N=C(C(C=5C=CC=CC=5)=NC4=CC=3)C=3C=CC=CC=3)C=C2N=C1C1=CC=CC=C1 QESBRXIXJOBVGC-UHFFFAOYSA-N 0.000 description 1
- SFTGSELZPLVANR-UHFFFAOYSA-N 6-[2,3-bis(furan-2-yl)quinoxalin-6-yl]-2,3-bis(furan-2-yl)quinoxaline Chemical compound O1C(=CC=C1)C1=NC2=CC=C(C=C2N=C1C=1OC=CC=1)C=1C=C2N=C(C(=NC2=CC=1)C=1OC=CC=1)C=1OC=CC=1 SFTGSELZPLVANR-UHFFFAOYSA-N 0.000 description 1
- DHXZNZLBPPDILC-UHFFFAOYSA-N 6-chloro-2,3-dipyridin-2-ylquinoxaline Chemical compound ClC=1C=C2N=C(C(=NC2=CC=1)C1=NC=CC=C1)C1=NC=CC=C1 DHXZNZLBPPDILC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 1
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- FSEXLNMNADBYJU-UHFFFAOYSA-N alpha-Phenylquinoline Natural products C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=N1 FSEXLNMNADBYJU-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- FAPDDOBMIUGHIN-UHFFFAOYSA-K antimony trichloride Chemical compound Cl[Sb](Cl)Cl FAPDDOBMIUGHIN-UHFFFAOYSA-K 0.000 description 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
- 239000012431 aqueous reaction media Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- NYENCOMLZDQKNH-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)bismuthanyl trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F NYENCOMLZDQKNH-UHFFFAOYSA-K 0.000 description 1
- BVLXNPRUOXPBII-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)gallanyl trifluoromethanesulfonate Chemical compound [Ga+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F BVLXNPRUOXPBII-UHFFFAOYSA-K 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- KOOMFXGDLMRWSN-UHFFFAOYSA-N n-phenylnitrous amide Chemical class O=NNC1=CC=CC=C1 KOOMFXGDLMRWSN-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Definitions
- the present invention relates to a new production process for quinoxalines. STATE OF THE ART
- the present invention relates to the condensation according to synthesis route "A", that is to say of o-phenylenediamines with 1,2-diketones. These condensation reactions are typically carried out in ethanol or acetone as the solvent under reflux in the presence of a catalyst. Numerous catalysts are known for this purpose, including e.g. B.
- the solvents tested were methanol, ethanol, THF, dichloromethane, acetonitrile, 1: 1 mixtures of THF or ethanol and water, and water alone, where I2 was added as a catalyst at 5 mol% in each case.
- the aim of the invention was against this background to develop a rapid, inexpensive and environmentally friendly process for the preparation of quinoxalines, in particular aromatically substituted quinoxalines, from correspondingly substituted o-phenylenediamines.
- the present invention achieves this aim by providing a process for the preparation of quinoxalines by condensation of optionally substituted o-phenylenediamine with a diketone according to the following reaction scheme: Scheme 4
- Ri, R2 and R3 are each independently hydrogen or a monovalent, saturated, unsaturated or aromatic hydrocarbon radical having 1 to 20 carbon atoms, one or more carbon atoms optionally being replaced by heteroatoms, each independently selected from O, N, S, F, CI and Br are selected and n is an integer from 0 to 4;
- radicals Ri and / or the radicals R2 and R3 are connected to one another and together with the atoms to which they are bonded form a saturated, unsaturated or aromatic ring and / or one Ri of two o-phenylenediamine molecules together for stand a chemical bond and thus form a diaminobenzidine;
- condensation reaction is carried out in water as a solvent by heating the reactants under pressure to a reaction temperature> 100 ° C.
- the process of the present invention is based on the surprising discovery by the inventors that o-phenylenediamines, although they are extremely unstable under the conditions prevailing in the inventive method and react within a few minutes, as will be shown in Comparative Example 1 later, nonetheless in good yields are condensable to the desired quinoxalines - even at temperatures above 200 ° C under high pressures, which is anything but gentle reaction conditions, and without the need for the addition of catalysts. It was also particularly surprising that aromatic diketones, such as. B. benzil and dimethoxybenzil, with which according to the prior art at room temperature only conversions of 10-30% were achieved even after 5 hours, the desired quinoxalines could be obtained within a very short time in yields of over 90%.
- the yields were about the same as when using pure water the addition of acetic acid apparently had no effect on the stability of the diamine under hydrothermal conditions, but this showed a clear catalytic effect.
- an aqueous solution of acetic acid more preferably an approximately 1 to approximately 10%, in particular an approximately 5%, aqueous solution of acetic acid is used as the aqueous solvent.
- the reaction mixture is heated to a reaction temperature of at least 200 ° C., in particular to a reaction temperature of about 230 ° C., in order to ensure the fastest possible condensation reactions.
- a reaction temperature of at least 200 ° C., in particular to a reaction temperature of about 230 ° C.
- pressures between 20 and 30 bar were generally established.
- the heating to the hydrothermal conditions is carried out using microwave radiation in the shortest possible time, specifically within just 2 minutes.
- the high reaction temperature need only be maintained for a period of not more than 10 minutes, preferably not more than 5 minutes.
- Ri and R2 are each aromatic radicals, which can sometimes be linked to one another, since the resulting quinoxalines could for the first time be produced in good yields within a short time using water as the sole solvent, and also conjugated aromatic systems which are valuable materials for the manufacture of optoelectronic components.
- the o-phenylenediamine is used in dimeric form, ie one Ri of two o-phenylenediamine molecules together form a chemical bond that connects these molecules to form a dimer, ie a diaminobenzidine, which in particular has 3, Is 3'-diaminobenzidine.
- dimeric quinoxalines with relatively high molecular weights have not previously been accessible in such a simple manner.
- a further catalyst in addition to acetic acid, can nonetheless be added in order to further increase the conversion of the condensation reaction in the short reaction times according to the present invention, even if the reaction takes place in a short time even without such an additional catalyst and can be carried out with satisfactory yields.
- the process according to the invention allows the desired quinoxalines to be synthesized in good yields within a few minutes of reaction time, without the need to add any catalyst.
- the invention also relates to a new substance synthesized for the first time by the inventors, namely the dimeric quinoxaline as a product of the later Example 14, i.e. H. 2,2 ', 3,3'-tetrakis (4-methoxyphenyl) -6,6'-dichinoxaline or 6- (2,3-bis (4-methoxyphenyl) quinoxalin-6-yl) -2,3-bis ( 4-methoxyphenyl) quinoxaline of the following formula (14):
- o-Phenylenediamine (64.9 mg, 0.6 mmol) was weighed together with 9,10-phenanthrene-quinone (124.9 mg, 0.6 mmol) into a glass microwave insert and mixed with 15 ml of dist. Water layered. A magnetic stir bar was added and the insert sealed and placed in a microwave reactor. The reaction mixture was heated to 230 ° C. over the course of 2 minutes with stirring and held at this temperature for 5 minutes. The reaction mixture was then cooled and the precipitated solid was filtered off. The product was washed with distilled water and dried overnight in a drying cabinet heated to 80 ° C. In this way, 127.9 mg (76.0% of theory) of the title compound were obtained.
- o-Phenylenediamine (42.3 mg, 0.4 mmol) was weighed together with the respective diketone (0.4 mmol) in a glass microwave insert and poured into 2 ml of either dist. Suspended water or 5% acetic acid, after which the insert was sealed and placed in a microwave reactor. The reaction mixture was heated to 230 ° C. within 1-2 minutes and held at this temperature for 5, 10 and 30 minutes, respectively. The reaction mixture was then cooled and the precipitated solid was filtered off. The product was washed with distilled water and dried overnight in a drying cabinet heated to 80 ° C.
- the title compound was determined using dist. Water as a solvent in a yield of 64% of theory. Th. After a reaction time of 5 min (Example 6a) and of 87% of theory. Th. After 30 min (Example 6b) and using 5% acetic acid as a solvent in a yield of 76% of theory. Th. After 5 min (Example 6c) and also from 87% of theory. Th. After 10 min (Example 6d) in each case as a yellow solid.
- the title compound was determined using dist. Water as a solvent in a yield of 63% of theory. Th. After a reaction time of 5 min (Example 7a) and 86% of theory. Th. After 30 min (Example 7b) and using 5% acetic acid as a solvent in a yield of 74% of theory. Th. After 5 min (Example 7c) and from 84% of the theory. Th. Obtained after 10 min (Example 7d) in each case as a gray solid.
- Example 8a The title compound was obtained using 5% acetic acid as a solvent in a yield of 76% of theory. Th. After a reaction time of 5 min (Example 8a) and of 86% of theory. Th. Obtained after 10 min (Example 8b) in each case as a yellow solid.
- Example 9a The title compound was obtained using 5% acetic acid as a solvent in a yield of 69% of theory. Th. After a reaction time of 5 min (Example 9a) and 80% of theory. Th. After 10 min (Example 9b) in each case as a yellow solid.
- the title compound was obtained using 5% acetic acid as a solvent in a yield of 71% of theory. Th. After a reaction time of 5 min (example 10a) and 80% d. Th. After 10 min (Example 10b) in each case as a yellow solid obtained.
- the title compound was obtained using 5% acetic acid as the solvent in a yield of 84% of theory. Th. After a reaction time of 5 min (Example 11 a) and 97% of theory. Th. After 10 min (Example 1 1 b) he hold each as a white solid.
- the title compound was obtained using 5% acetic acid as a solvent in a yield of 81% of theory. Th. After a reaction time of 5 min (Example 12a) and 93% of theory. Th. After 10 min (Example 12b) he holds each as a white solid.
- the title compound was obtained using 5% acetic acid as a solvent in a yield of 82% of theory. Th. After a reaction time of 5 min (Example 13a) and 93% of theory. Th. After 10 min (Example 13b) in each case as a yellow solid obtained.
- Example 15a The title compound was obtained using 5% acetic acid as a solvent in a yield of 83% of theory. Th. After a reaction time of 5 min (Example 15a) and 94% of theory. Th. After 10 min (Example 15b) in each case as a yellow solid obtained.
- o-phenylenediamine was used alone, i.e. without a reaction partner, with 15 ml of distilled water. Water was added and the mixture was heated to 200 ° C. overnight in a steel autoclave. After drying in a high vacuum, an FT-IR-ATR spectrum was recorded. and compared with a spectrum of the starting material before heating, the two curves being superimposed.
- Fig. 1 shows this comparison, the curve after exposure to hydrothermal conditions and those of the starting material are shown in bold. It can be seen that practically all of the characteristic bands had disappeared, which means that the o-phenylenediamine had reacted almost completely during the hydrothermal conditions.
- a rapid NMR analysis showed, however, that not (or not only) the o-quinonediimine or 2,3-diaminophenazine shown in Scheme 2, but a large number of reaction products, had arisen.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
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ATA76/2019A AT522210B1 (en) | 2019-02-27 | 2019-02-27 | Manufacturing process for quinoxalines |
PCT/EP2020/055176 WO2020174058A1 (en) | 2019-02-27 | 2020-02-27 | Method for producing quinoxalines |
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