EP3898574A1 - Procédé de production d'anilines substituées - Google Patents
Procédé de production d'anilines substituéesInfo
- Publication number
- EP3898574A1 EP3898574A1 EP19816767.8A EP19816767A EP3898574A1 EP 3898574 A1 EP3898574 A1 EP 3898574A1 EP 19816767 A EP19816767 A EP 19816767A EP 3898574 A1 EP3898574 A1 EP 3898574A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compounds
- formula
- iii
- alkyl
- trifluoromethyl
- 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
- 238000004519 manufacturing process Methods 0.000 title abstract description 4
- 150000001448 anilines Chemical class 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 156
- 238000006243 chemical reaction Methods 0.000 claims description 53
- 239000002904 solvent Substances 0.000 claims description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
- 239000003960 organic solvent Substances 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 229910052794 bromium Inorganic materials 0.000 claims description 23
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 22
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 239000000460 chlorine Substances 0.000 claims description 21
- -1 2-methyl-THF Chemical compound 0.000 claims description 20
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 15
- 239000011541 reaction mixture Substances 0.000 claims description 14
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 13
- 229940011051 isopropyl acetate Drugs 0.000 claims description 13
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 13
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 238000005660 chlorination reaction Methods 0.000 claims description 5
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 230000031709 bromination Effects 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- FKTXDTWDCPTPHK-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical group FC(F)(F)[C](F)C(F)(F)F FKTXDTWDCPTPHK-UHFFFAOYSA-N 0.000 claims description 2
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 239000000243 solution Substances 0.000 description 56
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 41
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
- 239000012071 phase Substances 0.000 description 25
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 230000002140 halogenating effect Effects 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- BBZVTTKMXRPMHZ-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoro-2-iodopropane Chemical compound FC(F)(F)C(F)(I)C(F)(F)F BBZVTTKMXRPMHZ-UHFFFAOYSA-N 0.000 description 18
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 16
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000004821 distillation Methods 0.000 description 12
- 238000002955 isolation Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000000538 analytical sample Substances 0.000 description 11
- 235000011054 acetic acid Nutrition 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 235000015320 potassium carbonate Nutrition 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- FSNCEEGOMTYXKY-JTQLQIEISA-N Lycoperodine 1 Natural products N1C2=CC=CC=C2C2=C1CN[C@H](C(=O)O)C2 FSNCEEGOMTYXKY-JTQLQIEISA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- NXWRKJGSRUCYEN-UHFFFAOYSA-N 2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)aniline Chemical compound NC1=C(Cl)C=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1Cl NXWRKJGSRUCYEN-UHFFFAOYSA-N 0.000 description 6
- ZFCOUBUSGHLCDT-UHFFFAOYSA-N 2-(trifluoromethoxy)aniline Chemical compound NC1=CC=CC=C1OC(F)(F)F ZFCOUBUSGHLCDT-UHFFFAOYSA-N 0.000 description 6
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 6
- PWDDQCRAKBGDTI-UHFFFAOYSA-N 4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)aniline Chemical compound NC1=CC=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1 PWDDQCRAKBGDTI-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 239000003444 phase transfer catalyst Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- JCQGIZYNVAZYOH-UHFFFAOYSA-M trihexyl(tetradecyl)phosphanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[P+](CCCCCC)(CCCCCC)CCCCCC JCQGIZYNVAZYOH-UHFFFAOYSA-M 0.000 description 4
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- SEQRDAAUNCRFIT-UHFFFAOYSA-N 1,1-dichlorobutane Chemical compound CCCC(Cl)Cl SEQRDAAUNCRFIT-UHFFFAOYSA-N 0.000 description 2
- FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 2
- RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 description 2
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 2
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 description 2
- CGNAIUUCOVWLLL-UHFFFAOYSA-N 2-(difluoromethoxy)aniline Chemical compound NC1=CC=CC=C1OC(F)F CGNAIUUCOVWLLL-UHFFFAOYSA-N 0.000 description 2
- VBLXCTYLWZJBKA-UHFFFAOYSA-N 2-(trifluoromethyl)aniline Chemical compound NC1=CC=CC=C1C(F)(F)F VBLXCTYLWZJBKA-UHFFFAOYSA-N 0.000 description 2
- SULCAUVYSILBCB-UHFFFAOYSA-N 2-bromo-1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)(Br)C(F)(F)F SULCAUVYSILBCB-UHFFFAOYSA-N 0.000 description 2
- IECTVYZUXRRZAK-UHFFFAOYSA-N 2-chloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethoxy)aniline Chemical compound NC1=C(Cl)C=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1OC(F)(F)F IECTVYZUXRRZAK-UHFFFAOYSA-N 0.000 description 2
- HTLCUFQJVRHFQM-UHFFFAOYSA-N 2-chloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethyl)aniline Chemical compound NC1=C(Cl)C=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1C(F)(F)F HTLCUFQJVRHFQM-UHFFFAOYSA-N 0.000 description 2
- RHQBQSSQBXDLAT-UHFFFAOYSA-N 2-chloro-6-(difluoromethoxy)-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)aniline Chemical compound NC1=C(Cl)C=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1OC(F)F RHQBQSSQBXDLAT-UHFFFAOYSA-N 0.000 description 2
- BHBBDCWGTJHGCX-UHFFFAOYSA-N 2-chloro-6-ethyl-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)aniline Chemical compound CCc1cc(cc(Cl)c1N)C(F)(C(F)(F)F)C(F)(F)F BHBBDCWGTJHGCX-UHFFFAOYSA-N 0.000 description 2
- FQPRLZDVXVSBBL-UHFFFAOYSA-N 2-ethyl-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)aniline Chemical compound CCC1=CC(C(F)(C(F)(F)F)C(F)(F)F)=CC=C1N FQPRLZDVXVSBBL-UHFFFAOYSA-N 0.000 description 2
- HWKOSANXMFQMMT-UHFFFAOYSA-N 4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-2-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1OC(F)(F)F HWKOSANXMFQMMT-UHFFFAOYSA-N 0.000 description 2
- JNVWIZVZNZAVRK-UHFFFAOYSA-N 4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-2-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(C(F)(F)F)C(F)(F)F)C=C1C(F)(F)F JNVWIZVZNZAVRK-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- BNIXVQGCZULYKV-UHFFFAOYSA-N pentachloroethane Chemical compound ClC(Cl)C(Cl)(Cl)Cl BNIXVQGCZULYKV-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- XTGYEAXBNRVNQU-UHFFFAOYSA-N 1,1,1,2,2,3,3-heptafluoro-3-iodopropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)I XTGYEAXBNRVNQU-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- PLSVLVAJUFTDOY-UHFFFAOYSA-N 2-bromo-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-methylaniline Chemical compound CC1=CC(C(F)(C(F)(F)F)C(F)(F)F)=CC(Br)=C1N PLSVLVAJUFTDOY-UHFFFAOYSA-N 0.000 description 1
- GGRVIMSAUGGXMP-UHFFFAOYSA-N 2-chloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-methylaniline Chemical compound ClC1=C(N)C(=CC(=C1)C(C(F)(F)F)(C(F)(F)F)F)C GGRVIMSAUGGXMP-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- WBUOVKBZJOIOAE-UHFFFAOYSA-N 3-chlorobenzonitrile Chemical compound ClC1=CC=CC(C#N)=C1 WBUOVKBZJOIOAE-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- YVBJAGGGYSGYID-UHFFFAOYSA-H FC(S(=O)(=O)[O-])(F)F.[Sc+3].[Fe+3].FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F Chemical compound FC(S(=O)(=O)[O-])(F)F.[Sc+3].[Fe+3].FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F.FC(S(=O)(=O)[O-])(F)F YVBJAGGGYSGYID-UHFFFAOYSA-H 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- XFTIKWYXFSNCQF-UHFFFAOYSA-N N,N-dipropylformamide Chemical compound CCCN(C=O)CCC XFTIKWYXFSNCQF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- PSYSDTIYBVGLHL-UHFFFAOYSA-N [Cl-].C(CCC)C(CCC[PH2+]CCCCCCCCCCCCCC)(CCCC)CCCC Chemical compound [Cl-].C(CCC)C(CCC[PH2+]CCCCCCCCCCCCCC)(CCCC)CCCC PSYSDTIYBVGLHL-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012868 active agrochemical ingredient Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- CVLBKOCGILILOW-UHFFFAOYSA-N bromobenzene;chloromethylbenzene Chemical compound BrC1=CC=CC=C1.ClCC1=CC=CC=C1 CVLBKOCGILILOW-UHFFFAOYSA-N 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
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000007973 cyanuric acids Chemical class 0.000 description 1
- QLVWOKQMDLQXNN-UHFFFAOYSA-N dibutyl carbonate Chemical group CCCCOC(=O)OCCCC QLVWOKQMDLQXNN-UHFFFAOYSA-N 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- QCAWEPFNJXQPAN-UHFFFAOYSA-N methoxyfenozide Chemical compound COC1=CC=CC(C(=O)NN(C(=O)C=2C=C(C)C=C(C)C=2)C(C)(C)C)=C1C QCAWEPFNJXQPAN-UHFFFAOYSA-N 0.000 description 1
- NZMAJUHVSZBJHL-UHFFFAOYSA-N n,n-dibutylformamide Chemical compound CCCCN(C=O)CCCC NZMAJUHVSZBJHL-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- UXPOJVLZTPGWFX-UHFFFAOYSA-N pentafluoroethyl iodide Chemical compound FC(F)(F)C(F)(F)I UXPOJVLZTPGWFX-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- HEZHYQDYRPUXNJ-UHFFFAOYSA-L potassium dithionite Chemical compound [K+].[K+].[O-]S(=O)S([O-])=O HEZHYQDYRPUXNJ-UHFFFAOYSA-L 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 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 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005497 tetraalkylphosphonium group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- AKUNSPZHHSNFFX-UHFFFAOYSA-M tributyl(tetradecyl)phosphanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC AKUNSPZHHSNFFX-UHFFFAOYSA-M 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/52—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/84—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
Definitions
- the present invention relates to a process for the preparation of compounds of the formula (I)
- a possible process for the preparation of compounds of the formula (I) or their precursors is described, for example, in EP1380568 and WO2016 / 174052.
- the preparation is carried out by perfluoroalkylation in the para position of anilines which are already substituted in the ortho and meto position.
- the processes described have the disadvantage that, depending on the substitution, the products are obtained in fluctuating, sometimes only moderate yields, or can be obtained in good yields exclusively by means of very waste-prone Fenton oxidation.
- the compounds of formula (I) have to be prepared in multi-stage processes. Further possible processes for the preparation of compounds of the formula (I) are also described in WO2016 / 174052 and also in US2010 / 0204504, EP2319830 and EP2325165.
- perfluoroalkylated anilines which can optionally also be substituted in the ortho position, are first prepared and isolated in the para position. These can then be halogenated in a further step in the meta or in the meta and orf / zo position to give compounds of the formula (I).
- a disadvantage of the processes described is in particular the need to isolate the perfluoroalkylated intermediates. On the one hand, this makes a complex, two-stage process with a higher amount of energy, time and waste necessary. In addition, because of their structure, the intermediates tend to decompose through polymerization and thus have only limited stability in concentrated form.
- R 1 represents chlorine or bromine
- R 2 represents Ci-C 4 haloalkyl
- R 3 represents cyano, halogen, optionally substituted by halogen or CN Ci-C 4 alkyl or represents optionally substituted by halogen Ci-C 4 alkoxy, starting from compounds of formula (II),
- R 3 represents hydrogen, cyano, halogen, optionally substituted with halogen or CN-substituted C 1 -C 4 -, alkyl or optionally substituted with halogen Ci-C 4 alkoxy, comprising the following steps (1) and (2)
- the process according to the invention has the advantage over the process described above that the desired compounds of the formula (I) are obtained in high yields and purities and at the same time the waste streams and process steps are reduced and the overall process can thus be operated more simply, more efficiently and therefore more cost-effectively.
- the method according to the invention enables the continuous avoidance of solvents which are undesirable in industrial processes in all steps.
- flalogen in the context of this invention preferably stands for chlorine, fluorine, bromine or iodine, particularly preferably for chlorine, fluorine or bromine.
- R 2 represents C 1 -C 4 -alkyl substituted with fluorine.
- R 2 for perfluoro-Ci-C 3 alkyl (CF 3 , C 2 F 5 or C 3 F 7 (n- or iso-propyl)).
- R 2 very particularly preferably represents Fleptafluoro-iso-propyl.
- R 3 for a substituent selected from CI, Br, F, Ci-C3-alkyl, C1-C3-alkyl substituted with flalogen, Ci-C3-alkoxy or Ci-C3-alkoxy substituted with flalogen.
- R 3 very particularly preferably represents CI, trifluoromethyl, trifluoromethoxy or difluoromethoxy.
- R 1 and R 3 both represent chlorine or bromine, particularly preferably chlorine.
- R 1 for chlorine or bromine
- R 2 for perfluoro-Ci-C 3 alkyl
- R 3 represents halogen, Ci-C 3 alkyl or fluoro substituted Ci-C 3 alkyl, Ci-C 3 alkoxy or fluoro substituted Ci-C 3 alkoxy.
- R 1 represents chlorine or bromine
- R 3 ' for a substituent selected from hydrogen, CI, Br, F, Ci-C 3 alkyl, halogen-substituted Ci-C 3 alkyl, Ci-C 3 alkoxy or halogen-substituted Ci-C 3 alkoxy.
- R 3 ' for hydrogen, CI, trifluoromethyl, trifluoromethoxy or difluoromethoxy.
- aniline aniline
- alkyl preferably a residue of a saturated, aliphatic hydrocarbon group having 1 to 12 1 to 6 and particularly preferably 1 to 4 carbon atoms understood, which can be branched or unbranched.
- C1-C12 alkyl radicals are methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, 1, 2-dimethylpropyl, hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl.
- alkoxy either alone or in combination with other terms, such as, for example, haloalkoxy, is understood here to mean an O-alkyl radical, the term “alkyl” having the meaning given above.
- aryl is understood according to the invention to mean an aromatic radical having 6 to 14 carbon atoms, preferably phenyl, naphthyl, anthryl or phenanthrenyl, particularly preferably phenyl.
- Residues substituted by halogen are halogenated one or more times to the maximum possible number of substituents.
- the halogen atoms can be the same or different.
- optionally substituted radicals can be mono- or polysubstituted, and in the case of multiple substitutions the substituents can be the same or different.
- the general or priority areas listed above apply accordingly to the overall process. These definitions can be combined with one another, i.e. also between the respective preferred areas.
- the compounds of the formula (II) are converted into compounds of the formula (III) using compounds of the formula R 2 -Y, where Y is iodine or bromine,
- the invention preferably between 0.9 and 2.0 equivalents, particularly preferably between 1.0 and 1.8 equivalents, very particularly preferably between 1.0 and 1.5 equivalents, based on the total amount of the compounds of the formula ( II), of the compounds of the formula R 2 -Y.
- the use of larger surpluses is chemically possible, but is not economically feasible.
- the compounds of the formula R 2 -Y are preferably in pure form or as a solution in the solvent preferred for the reaction in concentrations of 40-95% by weight, particularly preferably in Pure form or as a solution in a preferred organic solvent in concentrations of 60-90% by weight and very particularly preferably in pure form or as a solution in a preferred solvent in concentrations of 60-85% by weight.
- Preferred compounds of the formula R 2 -Y are, in particular, pentafluoroiodethane, heptafluoro-1-iodopropane, heptafluoro-2-iodopropane and heptafluoro-2-bromopropane, and heptafluoro-2-iodopropane and heptafluoro-2-bromo are particularly preferred -propane, heptafluoro-2-iodo-propane is very particularly preferred.
- the compounds of the formula (III) in step (1) can be prepared, for example, from the corresponding anilines in analogy to the methods described in JP 2012/153635 A and CN 106748807 A.
- a suitable organic solvent is preferably used in step (1).
- Suitable solvents are, for example: aromatic or aliphatic halogenated hydrocarbons, in particular aromatic or aliphatic chlorinated hydrocarbons, such as tetrachloroethane, dichloropropane, dichloromethane, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichlorethylene, pentachloroethane, difluorobenzene, chlorobenzene, bromobenzene, bromobenzene, bromobenzene, bromobenzene, bromobenzene, bromide and trichlorobenzene; Esters, especially methyl acetate, ethyl acetate, propyl (n- and iso) acetate or butyl acetate; Ethers, especially tetrahydrofuran (THF), 2-methyl-THF, cyclopen
- Preferred solvents are acetonitrile, methyl acetate, ethyl acetate, isopropyl acetate, tert-butyl methyl ether, cyclopentyl methyl ether, THF and methyl-THF.
- Acetonitrile, tert-butyl methyl ether, ethyl acetate and isopropyl acetate are very particularly preferred.
- the solvents can be used alone or in combination of two or more.
- Step (1) is preferably carried out in a two-phase system composed of one of the above-mentioned organic solvents and water according to the invention, for example in a ratio of 5: 1 to 1: 5 (organic solvent water), particularly preferably in a ratio of 5: 1 to 1: 2, very particularly preferably in a ratio of 2: 1 to 1: 2.
- Step (1) is preferably carried out in the presence of a phase transfer catalyst, which is preferably selected from quaternary ammonium salts (in particular tetra-n-butylammonium hydrogen sulfate, chloride or bromide) and tetraalkyl-phosphonium salts (in particular tri-n-butyl (tetradecyl ) butylphosphonium chloride or trihexyl-tetradecylphosphonium chloride).
- the phase transfer catalyst is particularly preferably selected from tetra-n-butylammonium hydrogen sulfate or tri-n-hexyl-tetradecylphosphonium chloride.
- the phase transfer catalyst is preferably used in a proportion between 0.005 and 0.06 equivalents, particularly preferably in a proportion between 0.01 and 0.05 equivalents, based on the total amount of compound (II) used.
- the catalyst is preferably used in pure form.
- Step (1) is preferably carried out in the presence of a reducing agent, for example sodium or potassium dithionite, particularly preferably sodium dithionite.
- a reducing agent for example sodium or potassium dithionite, particularly preferably sodium dithionite.
- preference is given to using between 0.9 and 2.0 equivalents, particularly preferably between 1.0 and 1.8 equivalents, very particularly preferably between 1.0 and 1.5 equivalents, based on the total amount of compound (II) used. , used.
- the reducing agent is preferably used in pure form.
- Step (1) is preferably carried out at an ambient temperature in the range from -10 ° C. to 80 ° C., particularly preferably in the range from 0 ° C. to 60 ° C., very particularly preferably in the range from -5 ° C. to 40 ° C.
- Step (1) is preferably carried out in the range of normal pressure (1013 hPa), e.g. B. in the range of 300 hPa to 5000 hPa or from 500 hPa to 2000 hPa, preferably as in the range of 1013 hPa ⁇ 200 hPa.
- the reaction time of the pefluoroalkylation in step (1) is preferably in the range from 3 to 48 hours, particularly preferably between 3 and 24 hours, very particularly preferably between 6 and 24 hours.
- the compounds R 2 -Y are preferably added by continuous dosing over a period of 2 to 10 hours, particularly preferably between 3 and 6 hours.
- Step (1) is preferably carried out under pH control.
- the pH of the reaction solution is preferably kept in a pH range between 3 and 7, particularly preferably in a pH range between 4 and 7.
- the pH control is preferably carried out both during the addition of the compounds R 2 -Y and during the subsequent reaction over the entire reaction time and by adding a suitable base known to the person skilled in the art, for example as a pure substance or aqueous solutions of (earth) Alkali carbonates, (earth) alkali hydrogen carbonates or (earth) alkali hydroxides.
- a suitable acid which is well known to the person skilled in the art, for example, carboxylic acids, such as acetic acid or propionic acid, mineral acids, such as hydrochloric acid or sulfuric acid, or sulfonic acids, such as methanesulfonic acid, to a preferred pH, in particular a pH of 4 to 5.
- carboxylic acids such as acetic acid or propionic acid
- mineral acids such as hydrochloric acid or sulfuric acid
- sulfonic acids such as methanesulfonic acid
- the compounds of formula (III) are reacted with a chlorinating or brominating agent to give compounds of formula (I).
- halogenating agent is used to represent chlorinating or brominating agents.
- halogen represents chlorine or bromine.
- Suitable halogenating agents are those known to those skilled in the art, such as e.g. Chlorine, bromine, an inorganic salt containing chlorine or bromine, or an organic molecule containing chlorine or bromine, in which the binding of an organic radical to the halogen atom is polarized, so that the chlorine or bromine atom has a partial support is positive thread, such as V-halosuccinimides, 1,3-dihalogen-5-5-dimethylhydantoins or halogenated cyanuric acids (organic halogenating compounds).
- Suitable halogenating agents are preferably chlorine, bromine or organic halogenating agents, which are particularly preferably selected from V-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), 1,3-dichloro-5-5-dimethylhydantoin (DCDMH), 1,3 -Dibromo-5-5-dimethylhydantoin (DBDMH), l, 3,5-trichlor-l, 3,5-triazine-2,4,6-trione (TCCA), l, 3,5-tribromo-l, 3rd , 5-triazine-2,4,6-trione or 1,3-dibromo-1,3,5-triazine-2,4,6-trione.
- NCS V-chlorosuccinimide
- NBS N-bromosuccinimide
- DCDMH 1,3-dichloro-5-5-dimethylhydantoin
- DBDMH 1,3 -Dibromo-5-5-d
- the halogenating compounds are very particularly preferably selected from chlorine, bromine, 1,3-dichloro-5-5-dimethylhydantoin (DCDMH), 1,3-dibromo-5-5-dimethylhydantoin (DBDMH), 1,3,5-trichloro -l, 3,5-triazine-2,4,6-trione,
- the halogenating agents can be used alone or in combination of two or more, as long as the compounds used carry the same halogen.
- the halogenating agent can be used in a proportion between 1.0 and 3.0 equivalents (mono-halogen compounds) or between 0.5 and 1.5 equivalents (dihalogen compounds) or 0.3 and 1.0 equivalents (trihalogen compounds) and preferably between 1.0 and 2.5 equivalents (monohalogen compounds) or between 0.5 and 0.8 equivalents (dihalogen compounds) or between 0.33 and 0.75 equivalents (Trihalogen compounds), based on the total amount of compound (III) used.
- an excess of the halogenating agent can be neutralized after complete conversion determined by HPLC a by adding a reducing agent which is well known to the person skilled in the art, for example (earth) alkali metal sulfites, (earth) alkali metal dithionites or (earth) alkali metal thiosulfates.
- the reducing agents can preferably be used as a pure substance or as an aqueous solution, for example as a saturated aqueous solution.
- the halogenating agent can be present in pure form as a solid or as a suspension or solution in a suitable organic solvent which is inert under the reaction conditions, in particular in the solvent selected for the reaction, preferably in a concentration of 40-90% by weight, particularly preferably in a Concentration of 60-95% by weight.
- suitable organic solvents are in particular the preferred solvents mentioned below for step (2).
- Suitable acids could preferably be selected from the mineral acids familiar to the person skilled in the art, for example sulfuric acid, hydrochloric acid and hydrofluoric acid, sulfonic acids, for example methanesulfonic acid, trifluoromethanesulfonic acid and 4-toluenesulfonic acid, carboxylic acids, for example trifluoroacetic acid and trichloroacetic acid and Lewis acids, for example iron (III) - and Scandium (III) trifluoromethanesulfonate.
- mineral acids familiar to the person skilled in the art
- sulfonic acids for example methanesulfonic acid, trifluoromethanesulfonic acid and 4-toluenesulfonic acid
- carboxylic acids for example trifluoroacetic acid and trichloroacetic acid and Lewis acids, for example iron (III) - and Scandium (III) trifluoromethanesulfonate.
- the reaction is preferably carried out in a temperature range from -78 to 200 ° C., particularly preferably at temperatures between -20 to 100 ° C. and very particularly preferably between 0 ° C. and 50 ° C.
- the reaction can be carried out under elevated or reduced pressure. However, it is preferably carried out under normal pressure, for example in the range from 1013 hPa + 300 hPa, or in the range from 1013 hPa + 100 hPa, or in the range from 1013 hPa ⁇ 50 hPa.
- Step (2) is preferably carried out in a suitable organic solvent. Suitable diluents or solvents for carrying out step (2) are in principle all organic solvents which are inert under the specific reaction conditions.
- aromatic or aliphatic halogenated hydrocarbons in particular aromatic or aliphatic chlorinated hydrocarbons, such as tetrachloroethane, dichloropropane, dichloromethane, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichlorethylene, pentachloroethane, difluorobenzene, 1, 2-chlorobenzene, bromobenzene, 1, 2-chlorobenzene, bromobenzene, bromobenzene Chlorotoluene or trichlorobenzene; Nitriles, especially acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile or m-chlorobenzonitrile; optionally substituted aliphatic, cycloaliphatic or aromatic hydrocarbons, in particular pentane, hexane, heptane,
- Preferred diluents or solvents are aromatic or aliphatic halogenated hydrocarbons, in particular chlorobenzene, dichlorobenzene, dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride; Esters, especially ethyl acetate, isopropyl acetate and butyl acetate; Amides, especially DMF, DMAC and NMP; Ethers, especially tetrahydrofuran (THF), 2-methyl-THF, tert-butyl methyl ether or cyclopentyl methyl ether; Nitriles, especially acetonitrile or propionitrile or carboxylic acids, especially acetic acid or n-propanoic acid.
- aromatic or aliphatic halogenated hydrocarbons in particular chlorobenzene, dichlorobenzene, dichloromethane, chloroform, 1,2-dichloroethane or carbon tetrachloride;
- the solvent is selected from ethyl acetate, isopropyl acetate, tert-butyl methyl ether, cyclopentyl methyl ether, THF, 2-methyl-THF or acetonitrile.
- Acetonitrile, tert-butyl methyl ether, ethyl acetate and isopropyl acetate are very particularly preferred.
- the solvents can be used alone or in combination of two or more.
- the duration of the halogenation of the compounds of the formula (III) is preferably in the range from 0.5 h to 10 h, particularly preferably in the range from 0.25 h to 5 h. A longer reaction time is possible, but not useful from an economic point of view.
- the halogenating agent can be added to the other reactants in one portion or by metering over a longer period of time. Under certain circumstances, it may also be advantageous to convert a solution of the compound (III) into a solution or suspension in a solvent mentioned for step (2) of the halogenating agent in a preferred solvent for step (2).
- the duration of the metering can be in a preferred range from 0.5 to 6 hours, particularly preferably from 1 to 4 hours. Longer dosing times are also possible from a technical point of view, but are not sensible from an economic point of view.
- the addition or metering is preferably carried out in a temperature range from -78 to 200 ° C., particularly preferably at temperatures between -20 to 100 ° C. and very particularly preferably between 0 ° C. and 50 ° C.
- the temperature at which metering is carried out corresponds to the reaction temperature.
- step (1) and step (2) the same organic solvent is used in step (1) and step (2).
- the solvent in both steps is preferably selected from the group of the esters, the ethers or the nitriles, particularly preferably the solvent is selected from ethyl acetate, isopropyl acetate, tert-butyl methyl ether, cyclopentyl methyl ether, THF, methyl-THF and acetonitrile .
- Acetonitrile, tert-butyl methyl ether, ethyl acetate and isopropyl acetate are very particularly preferred.
- the solvents mentioned can be used alone or in combination of two or more.
- the process according to the invention is characterized in that the compounds of the formula (III) are not isolated from the reaction mixture from step (1) before step (2).
- isolated in the context of the present invention means a complete separation of the compounds of the formula (III) from the reaction mixture, that is to say, for example, from all solvents and salts by means of separation processes which are generally known to the person skilled in the art.
- isolated in the sense of the present invention means that after step (1) and before step (2), the entire organic solvent from step (1) is never removed.
- step (1) The compounds of the formula (III) from step (1) are preferably used directly as a solution in the organic solvent of step (1) in step (2).
- reaction volumes in the form of solids, liquids or suspensions for example in the form of solid, dissolved or suspended halogenating agents, or solvents (the same solvent as in the first step or a further solvent) can be added during the reaction sequence.
- the addition of acids or bases and the partial or complete removal of aqueous constituents of the reaction mixture between reaction steps (1) and (2) are possible.
- step (1) It is particularly advantageous if no organic solvent is actively removed after step (1).
- the active removal of the organic solvent is generally the removal of the organic solvent by means of distillation, if appropriate with thermal action on the reaction mixture, under normal or reduced conditions! Pressure understood.
- step (1) and step (2) take place in the same reaction vessel.
- the person skilled in the art will choose from the start a reaction vessel which can hold all the volumes for reaction (1) and (2).
- reaction sequence is a telescoped reaction in one or more vessels, preferably one vessel.
- the method according to the invention preferably consists of steps (1) and (2).
- step (1) and / or step (2) can also be carried out several times, for example two or three times, in the same reaction vessel without further working up.
- the reaction mixture from step (1) for example after complete conversion according to HPLC a, can again be mixed with the compound of the formula (II) and a reducing agent according to the invention and by metering in a compound R 2 -Y under pH control to give a compound of the formula (III) be implemented. This process can be repeated again or the reaction mixture can be treated further according to the invention.
- the reaction mixture from step (2) can again be mixed with compound of the formula (III) and then further converted into compounds of the formula (I) by adding a halogenating agent according to the invention.
- Scheme 1 gives an overall schematic representation of the method according to the invention with both steps. Reaction conditions and reactants are selected in accordance with the preferred and preferred embodiments of the invention described above. All variables in formulas (I), (II), (III) and R 2 -Y are defined as described above.
- the compounds of formula (II) are placed in a mixture of an organic solvent and water and after adding a phase transfer catalyst according to the invention, for example tetra-n-butylammonium hydrogen sulfate or tri-n-hexyl (tetradecyl) phosphonium chloride, and a reducing agent according to the invention, for. B. sodium dithionite, preferably at -10 ° C to 80 ° C, particularly preferably 0 ° C to 60 ° C for 2 h to 10 h, after which the pH before starting the metering by a suitable acid, for example acetic acid 4 to 5 was set, with a perfluoroalkylating agent according to the invention, e.g. B.
- a phase transfer catalyst for example tetra-n-butylammonium hydrogen sulfate or tri-n-hexyl (tetradecyl) phosphonium chloride
- a reducing agent according to the invention for. B. sodium
- the pH of the reaction mixture is preferably kept in a range from 3 to 7 during the entire reaction period by adding a suitable base, as a solid or as an aqueous solution, for example 40% by weight aqueous potassium carbonate solution.
- a suitable base as a solid or as an aqueous solution, for example 40% by weight aqueous potassium carbonate solution.
- the aqueous phase is separated off, the organic phase optionally with water or aqueous hydrochloric acid, for. B. 5 wt.% Or 25 wt.%, Washed and the organic phase, containing compounds of formula (III) preferably at -20 ° C to 100 ° C, particularly preferably at 0 ° C to 50 ° C, with a halogenating agent , e.g.
- the compounds of the formula (II) are introduced in a mixture of an organic solvent and water and, after adding a phase transfer catalyst according to the invention, for. B. tetra-n-butylammonium hydrogen sulfate or tri-n-hexyl (tetradecyl) phosphonium chloride, and a reducing agent according to the invention, for. B. Sodium dithionite, preferably at -10 ° C. to 80 ° C., particularly preferably 0 ° C.
- the pH of the reaction mixture is preferably kept in a range from 3 to 7 during the entire reaction period by adding a suitable base, as a solid or as an aqueous solution, for example 40% by weight aqueous potassium carbonate solution.
- a suitable base as a solid or as an aqueous solution, for example 40% by weight aqueous potassium carbonate solution.
- sodium dithionite preferably at -10 ° C to 80 ° C, particularly preferably 0 ° C to 60 ° C over 2 h to 10 h with a perfluoroalkylating agent according to the invention, for example heptafluoro-2-iodo-propane.
- the pH of the reaction mixture is preferably kept in a range from 3 to 7 during the entire reaction period by adding a suitable base, as a solid or as an aqueous solution, for example aqueous potassium carbonate solution.
- the process can optionally be repeated again or the aqueous phase separated, the organic phase optionally washed with water or aqueous hydrochloric acid, for example 5% by weight or 25% by weight, and the organic phase containing compounds of Formula (III) preferably at -20 ° C to 100 ° C, particularly preferably at 0 ° C to 50 ° C, with a halogenating agent, for. B. as a solid or solution in an organic solvent according to the invention, preferably over 0.5 h to 6 h.
- any excess halogenating agent which may be present is neutralized by adding a reducing agent, for example as a pure substance or aqueous solution, and the compounds of the formula (I) are isolated. (Step (1) (double) and (2))
- the compounds of the formula (II) are initially introduced into a mixture of ethyl acetate and water and, after addition of tetra-n-butylammonium hydrogen sulfate and sodium dithionite, at 0 ° C. to 60 ° C., after which the pH, if necessary, before starting the dosing with acetic acid 4 to 5 was set, heptafluoro-2-iodopropane was added over 3 h to 6 h.
- the pH of the reaction mixture is kept in a range from 4 to 7 during the entire metering and reaction period by adding a 40% by weight aqueous potassium carbonate solution.
- the aqueous phase is separated off, the organic phase optionally with water or aqueous hydrochloric acid, for example. 5% by weight or 25% by weight, and the organic phase, containing compounds of the formula (III), preferably at 0 ° C. to 50 ° C., with chlorine or 1,3,5-trichloro-1,3,5- triazine-2,4,6-trione (TCCA) (chlorination) or bromine or 1,3-dibromo-5-5-dimethylhydantoin (DBDMH) (bromination) over 1 h to 4 h.
- TCCA 1,3,5-trichloro-1,3,5- triazine-2,4,6-trione
- DBDMH 1,3-dibromo-5-5-dimethylhydantoin
- step (2) After the addition was complete, the mixture was stirred for a further 5 h at approx. 20-22 ° C at the same pH. A conversion of 94% to the desired product was detected by means of HPLC a) . The phases were separated and the organic phase was then used in step (2) without further treatment.
- the phases were then separated and the aqueous phase was extracted in succession with a mixture of 100 ml of ethyl acetate and 50 ml of n-heptane and a mixture of 50 ml of ethyl acetate and 25 ml of n-heptane.
- the combined organic phases were washed twice with 100 mL 20% by weight NaCl solution and the product obtained as a red-brown oil after removal of the solvent: yield 200.0 g (95% of theory).
- the slightly cloudy solution was then mixed with 10 mL aqueous, saturated Na2SC> 3 solution and 30 mL water. After separating the phases, diluting the organic phase with 50 mL ethyl acetate and then washing the organic phase with 30 mL water, and removing the solvent under reduced pressure, the product was obtained as a beige-orange solid: yield 9.7 g (98% of theory ).
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