CH615146A5 - Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid - Google Patents
Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid Download PDFInfo
- Publication number
- CH615146A5 CH615146A5 CH952775A CH952775A CH615146A5 CH 615146 A5 CH615146 A5 CH 615146A5 CH 952775 A CH952775 A CH 952775A CH 952775 A CH952775 A CH 952775A CH 615146 A5 CH615146 A5 CH 615146A5
- Authority
- CH
- Switzerland
- Prior art keywords
- product
- acid
- stage
- phenol
- difluorobiphenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 31
- 238000002360 preparation method Methods 0.000 title claims description 16
- 230000008569 process Effects 0.000 title claims description 15
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 title claims description 8
- 238000010992 reflux Methods 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 19
- -1 alkali metal salt Chemical class 0.000 claims description 17
- JVHAJKHGPDDEEU-UHFFFAOYSA-N 2,4-difluoro-1-phenylbenzene Chemical group FC1=CC(F)=CC=C1C1=CC=CC=C1 JVHAJKHGPDDEEU-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 12
- 239000012954 diazonium Substances 0.000 claims description 12
- ASOVDRYKVVVCIA-UHFFFAOYSA-N 4-(2,4-difluorophenyl)phenol Chemical compound C1=CC(O)=CC=C1C1=CC=C(F)C=C1F ASOVDRYKVVVCIA-UHFFFAOYSA-N 0.000 claims description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 10
- 230000021523 carboxylation Effects 0.000 claims description 10
- 238000006473 carboxylation reaction Methods 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 10
- 238000007127 saponification reaction Methods 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 238000005727 Friedel-Crafts reaction Methods 0.000 claims description 9
- 150000001989 diazonium salts Chemical class 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 230000010933 acylation Effects 0.000 claims description 8
- 238000005917 acylation reaction Methods 0.000 claims description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 7
- 239000011707 mineral Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 150000001447 alkali salts Chemical class 0.000 claims description 5
- 150000008064 anhydrides Chemical class 0.000 claims description 5
- 239000001569 carbon dioxide Substances 0.000 claims description 5
- DZKRDHLYQRTDBU-UPHRSURJSA-N (z)-but-2-enediperoxoic acid Chemical compound OOC(=O)\C=C/C(=O)OO DZKRDHLYQRTDBU-UPHRSURJSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 150000001879 copper Chemical class 0.000 claims description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 6
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 3
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 38
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical group CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000004744 fabric Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- SKRDXYBATCVEMS-UHFFFAOYSA-N isopropyl nitrite Chemical compound CC(C)ON=O SKRDXYBATCVEMS-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical class COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- HSNQVADZWQJQJJ-UHFFFAOYSA-N 1-[4-(2,4-difluorophenyl)phenyl]ethanone Chemical group C1=CC(C(=O)C)=CC=C1C1=CC=C(F)C=C1F HSNQVADZWQJQJJ-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- 238000007065 Kolbe-Schmitt synthesis reaction Methods 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 2
- 150000004074 biphenyls Chemical class 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- LZDSILRDTDCIQT-UHFFFAOYSA-N dinitrogen trioxide Chemical compound [O-][N+](=O)N=O LZDSILRDTDCIQT-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Chemical class CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 1
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- YCCQGFYAVUTQFK-UHFFFAOYSA-N 2,3-difluoroaniline Chemical compound NC1=CC=CC(F)=C1F YCCQGFYAVUTQFK-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical class OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ZPTDYZFKYMQWRT-UHFFFAOYSA-N 4-methoxycarbonylbenzenecarboperoxoic acid Chemical compound COC(=O)C1=CC=C(C(=O)OO)C=C1 ZPTDYZFKYMQWRT-UHFFFAOYSA-N 0.000 description 1
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 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
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N Methyl salicylate Natural products COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000006149 azo coupling reaction Methods 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000005626 carbonium group Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- NHADDZMCASKINP-HTRCEHHLSA-N decarboxydihydrocitrinin Natural products C1=C(O)C(C)=C2[C@H](C)[C@@H](C)OCC2=C1O NHADDZMCASKINP-HTRCEHHLSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 238000006902 nitrogenation reaction Methods 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
- C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
- C07C49/813—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/15—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction of organic compounds with carbon dioxide, e.g. Kolbe-Schmitt synthesis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49062074A | 1974-07-22 | 1974-07-22 | |
| US56720175A | 1975-04-16 | 1975-04-16 | |
| US05/571,165 US3992459A (en) | 1975-05-01 | 1975-05-01 | Preparation of biphenyl compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH615146A5 true CH615146A5 (en) | 1980-01-15 |
Family
ID=27413871
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH952775A CH615146A5 (en) | 1974-07-22 | 1975-07-21 | Process for the preparation of 5-(2,4-difluorophenyl)-salicylic acid |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5134135A (OSRAM) |
| CH (1) | CH615146A5 (OSRAM) |
| DE (1) | DE2532559C3 (OSRAM) |
| DK (1) | DK145643C (OSRAM) |
| FR (1) | FR2288729A1 (OSRAM) |
| GB (2) | GB1496231A (OSRAM) |
| IE (1) | IE41582B1 (OSRAM) |
| LU (1) | LU73032A1 (OSRAM) |
| NL (1) | NL188689C (OSRAM) |
| NO (1) | NO143874C (OSRAM) |
| SE (1) | SE428560B (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4216340A (en) * | 1979-05-02 | 1980-08-05 | Merck & Co., Inc. | Preparation of 5-(2,4-difluorophenyl)salicylic acid and derivatives |
| IT1133963B (it) * | 1980-10-21 | 1986-07-24 | D & D Srl | Derivati piridossinici ad attivita' terapeutica,procedimento per la loro preparazione e relative composizioni farmaceutiche |
| US4482502A (en) * | 1983-04-25 | 1984-11-13 | Ethyl Corporation | Preparation of biaryl compounds |
| JPH0582493U (ja) * | 1992-04-06 | 1993-11-09 | 株式会社エースプレミアム | 走行玩具 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO120372B (OSRAM) * | 1966-09-08 | 1970-10-12 | Merck & Co Ltd | |
| US3714226A (en) * | 1970-06-09 | 1973-01-30 | Merck & Co Inc | Phenyl benzoic acid compounds |
| GB1359987A (en) * | 1970-10-12 | 1974-07-17 | Boots Co Ltd | 2-substituted biphenylyl propionic acids |
| JPS4916419A (OSRAM) * | 1972-05-31 | 1974-02-13 |
-
1975
- 1975-07-07 SE SE7507764A patent/SE428560B/xx not_active IP Right Cessation
- 1975-07-08 NL NLAANVRAGE7508127,A patent/NL188689C/xx not_active IP Right Cessation
- 1975-07-09 DK DK310075A patent/DK145643C/da not_active IP Right Cessation
- 1975-07-10 NO NO752482A patent/NO143874C/no unknown
- 1975-07-16 IE IE1582/75A patent/IE41582B1/en unknown
- 1975-07-16 GB GB29879/75A patent/GB1496231A/en not_active Expired
- 1975-07-16 GB GB6938/77A patent/GB1496232A/en not_active Expired
- 1975-07-17 FR FR7522332A patent/FR2288729A1/fr active Granted
- 1975-07-21 CH CH952775A patent/CH615146A5/de not_active IP Right Cessation
- 1975-07-21 LU LU73032A patent/LU73032A1/xx unknown
- 1975-07-21 DE DE2532559A patent/DE2532559C3/de not_active Expired
- 1975-07-22 JP JP50088944A patent/JPS5134135A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| NO752482L (OSRAM) | 1976-01-23 |
| NO143874C (no) | 1981-04-29 |
| LU73032A1 (OSRAM) | 1976-07-01 |
| NL188689B (nl) | 1992-04-01 |
| DK310075A (da) | 1976-01-23 |
| GB1496231A (en) | 1977-12-30 |
| FR2288729B1 (OSRAM) | 1977-12-09 |
| NL7508127A (nl) | 1976-01-26 |
| NL188689C (nl) | 1992-09-01 |
| FR2288729A1 (fr) | 1976-05-21 |
| DK145643C (da) | 1983-07-11 |
| DK145643B (da) | 1983-01-10 |
| JPS5134135A (en) | 1976-03-23 |
| SE428560B (sv) | 1983-07-11 |
| DE2532559A1 (de) | 1976-02-05 |
| GB1496232A (en) | 1977-12-30 |
| NO143874B (no) | 1981-01-19 |
| SE7507764L (sv) | 1976-01-23 |
| IE41582B1 (en) | 1980-02-13 |
| JPS569496B2 (OSRAM) | 1981-03-02 |
| DE2532559C3 (de) | 1979-10-04 |
| DE2532559B2 (de) | 1979-02-15 |
| IE41582L (en) | 1976-01-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |