US20220073442A1 - Separation of phenol isomer - Google Patents
Separation of phenol isomer Download PDFInfo
- Publication number
- US20220073442A1 US20220073442A1 US17/526,316 US202117526316A US2022073442A1 US 20220073442 A1 US20220073442 A1 US 20220073442A1 US 202117526316 A US202117526316 A US 202117526316A US 2022073442 A1 US2022073442 A1 US 2022073442A1
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- United States
- Prior art keywords
- compound
- base
- acid
- mixture
- solvents
- Prior art date
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- Abandoned
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- 238000000926 separation method Methods 0.000 title description 9
- 150000002989 phenols Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 111
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 238000000034 method Methods 0.000 claims abstract description 49
- 239000002904 solvent Substances 0.000 claims description 53
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 50
- 239000002585 base Substances 0.000 claims description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 47
- 239000002244 precipitate Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 17
- 239000002184 metal Substances 0.000 claims description 17
- 239000002798 polar solvent Substances 0.000 claims description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 12
- 239000012454 non-polar solvent Substances 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- -1 naphtha Chemical compound 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 4
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 150000002334 glycols Chemical class 0.000 claims description 3
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- WVUYYXUATWMVIT-UHFFFAOYSA-N 1-bromo-4-ethoxybenzene Chemical compound CCOC1=CC=C(Br)C=C1 WVUYYXUATWMVIT-UHFFFAOYSA-N 0.000 claims description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims description 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims description 2
- KSNKQSPJFRQSEI-UHFFFAOYSA-N 3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-N 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 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 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 229940075419 choline hydroxide Drugs 0.000 claims description 2
- 238000010908 decantation Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 150000002357 guanidines Chemical class 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229940071870 hydroiodic acid Drugs 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical group [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 150000004968 peroxymonosulfuric acids Chemical class 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 239000000463 material Substances 0.000 description 17
- YNWKEXMSQQUMEL-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1Cl YNWKEXMSQQUMEL-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000003849 aromatic solvent Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 9
- NBZPDMNDTOEKMG-UHFFFAOYSA-N CC1=C(O)C=CC(C(F)(F)F)=C1 Chemical compound CC1=C(O)C=CC(C(F)(F)F)=C1 NBZPDMNDTOEKMG-UHFFFAOYSA-N 0.000 description 8
- SUIZARUATMVYRT-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)phenol Chemical compound OC1=CC(C(F)(F)F)=CC=C1Cl SUIZARUATMVYRT-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 4
- 125000003944 tolyl group Chemical group 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- ZIWHJZAPIYYSPN-UHFFFAOYSA-N CC1=C(Cl)C=CC(C(F)(F)F)=C1 Chemical compound CC1=C(Cl)C=CC(C(F)(F)F)=C1 ZIWHJZAPIYYSPN-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- JDTMUJBWSGNMGR-UHFFFAOYSA-N 1-nitro-4-phenoxybenzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=CC=C1 JDTMUJBWSGNMGR-UHFFFAOYSA-N 0.000 description 1
- CDMGNVWZXRKJNS-UHFFFAOYSA-N 2-benzylphenol Chemical class OC1=CC=CC=C1CC1=CC=CC=C1 CDMGNVWZXRKJNS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical class OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 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
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/685—Processes comprising at least two steps in series
-
- 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
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/86—Purification; separation; Use of additives, e.g. for stabilisation by treatment giving rise to a chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/26—Halogenated derivatives monocyclic monohydroxylic containing halogen bound to ring carbon atoms
Definitions
- the present subject matter relates to a process for separating compound (I) from a mixture comprising compound (I).
- the present subject matter also relates to a process for separating compound (I) from a mixture comprising compound (I) and compound (II).
- Compound (I) is often used as a starting material.
- Compound (I) can be obtained as a by-product and/or residual waste in different manufacturing process such as described in U.S. Pat. No. 4,046,798.
- the compound (I) may exist in a mixture with 2-chloro-5-(trifluoromethyl)-phenol (compound (II)).
- the residual waste also may comprise unknown impurities.
- impurities can react in parallel synthetic pathways, creating a need for extra further purification steps leading to additional costs.
- undesirable side-reactions require an excess of reagents, decrease yields, and increase costs and waste.
- U.S. Pat. No. 2,016,848 discloses a method of seperating orto and para benzyl phenol isomers via converting the compounds to their salt form and filtrating for one of the isomers.
- U.S. Pat. No. 4,366,329 discloses a method of seperating meta and para bromo phenol isomers via sodium salt derivative.
- Separation of compounds depends on the specific structure of the compound to be isolated.
- the position and location of the functional groups influence the separation method and conditions.
- the present invention provides a process for separating compound (I), or a salt thereof, from a mixture comprising the compound (I),
- the term “about” specifically includes ⁇ 10% from the indicated values in the range.
- the endpoints of all ranges directed to the same component or property herein are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges.
- the present invention provides a process for separating compound (I), or a salt thereof, from a mixture comprising the compound (I),
- the mixture further comprises compound (II)
- the process described herein may be used to separate compound (I) from mixtures with any compound (I) to compound (II) ratio.
- the ratio of compound (I) to compound (II) in the mixture is from 1:1000 to 1000:1.
- the ratio of compound (I) to compound (II) in the mixture is from 90:10 to 70:30. In some embodiments, the ratio of compound (I) to compound (II) in the mixture is 90:10, 85:15, or 80:20, 75:25, or 70:30.
- the ratio of compound (I) to compound (II) in the mixture is 88:11.
- the mixture which comprises compound (I) and compound (II) is a solution.
- the concentration of the compound (I) in the solution is from about 1% to 99%.
- the resulting precipitate material is a metal salt.
- the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 1000:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 500:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 200:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 100:1.
- the ratio of compound (I) to compound (II) in the resulting precipitate material is 77:0.4.
- the ratio of compound (I) to compound (II) in the resulting precipitate material is 98.15:1.85.
- the ratio of compound (I) to compound (II) in the resulting precipitate material is 93:0.2.
- the purity of compound (I) in the resulting precipitate material is 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more. In some embodiment, the purity of compound (I) in the resulting precipitate material is 80%, 85%, 90%, 95%, or 99%.
- the purity of compound (I) in the resulting precipitate material is 93%.
- the process further comprises neutralization of the metal salt with an acid.
- the metal salt of compound (I) is neutralized with an acid.
- the acid is an organic acid.
- Organic acids that may be used include but are not limited to carboxylic acids such as citric acid, fumaric acid, phthalic acid, maleic acid, malic acid, oxalic acid, adipic acid, glutaric acid, 2-methyl glutaric acid, succinic acid and tartaric acid, tri fluoro methyl acetic acid, p-toluene sulfonic acid or any combination thereof.
- carboxylic acids such as citric acid, fumaric acid, phthalic acid, maleic acid, malic acid, oxalic acid, adipic acid, glutaric acid, 2-methyl glutaric acid, succinic acid and tartaric acid, tri fluoro methyl acetic acid, p-toluene sulfonic acid or any combination thereof.
- the acid is an inorganic acid.
- Inorganic acids that may be used include but are not limited to hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, persulfuric acid or any combination thereof.
- the mixture reacts with the base in the presence of at least two solvents.
- the mixture reacts with the base in the presence of at least three solvents.
- the mixture reacts with the base in the presence of at least four solvents.
- At least one of the solvents is a polar solvent.
- the polar solvent is an organic polar solvent.
- the organic polar solvent is dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), glycols, sulfolan, mono and di-glymes, acetamide, glycerine, ACN, nitro ethane or any combination thereof.
- the organic polar solvent is an alcohol.
- the alcohol is methanol, ethanol or propanol. In preferred embodiments, the alcohol is ethanol.
- At least 1% of the total volume of the solvent is polar solvent.
- At least one of the solvents is a nonpolar solvent.
- the nonpolar solvent is an organic nonpolar solvent.
- the nonpolar solvent is nonpolar aromatic solvent.
- the nonpolar aromatic solvent is toluene, xylene, mono chloro benzene (MCB), naphtha, or any combination thereof.
- the nonpolar aromatic solvent is toluene.
- the naphtha is light naphtha. In some embodiments, the naphtha is heavy naphtha. In some embodiments, the naphtha is petroleum naphtha. In some embodiments, the solvent naphtha is the Solvesso® grades from ExxonMobil Chemical, especially Solvesso® 100 (CAS No. 64742-95-6), Solvesso® 150 (CAS No. 64742-94-5), and Solvesso® 200 (CAS No. 64742-94-5).
- the nonpolar aromatic solvent has a flashpoint of about 100° F. to about 200° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 100° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 150° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 200° F.
- none of the solvents is a nonpolar aromatic solvent.
- the nonpolar solvent is pentane, hexane, or dichloromethane (DCM).
- one of the solvents is water.
- the water is added to the reaction mixture.
- the water is formed during the reaction.
- the water is formed with addition of the base into the reaction mixture.
- At least 1% of the total volume of the solvent is water.
- the mixture is solution. In some embodiments, the mixture is solid.
- the concentration of water in the aqueous solution is not more than 25%. In some embodiments, the concentration of water in the aqueous solution is 10%. In some embodiments, the concentration of water in the aqueous solution is 1%.
- the mixture reacts with the base in the presence of one solvent wherein the solvent is ethanol. In some embodiments, the mixture reacts with the base in the presence of at least one solvent wherein one of the solvent is ethanol.
- the mixture reacts with the base in the presence of two solvents wherein the two solvents are toluene and ethanol. In some embodiments, the mixture reacts with the base in the presence of at least two solvents and two of the solvents are toluene and ethanol.
- the mixture reacts with the base in the presence of three solvents wherein the three solvents are toluene, water, and ethanol. In some embodiments, the mixture reacts with the base in the presence of at least three solvents and three of the at least three solvents are toluene, water, and ethanol.
- the base is an organic base. In some embodiments, the base is an inorganic base.
- the base is an alkali metal base. In some embodiments, the base is an earth alkaline metal base. In some embodiments, the alkaline metal is sodium, lithium, or potassium. In some embodiments, the earth alkaline metal is magnesium or calcium.
- the organic base is triethylamine, trimethylamine, ammonia, ammonium hydroxide, pyridine, guanidines, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, or 1,4-diazabicyclo[2.2.2]octane (DABCO).
- the inorganic base is hydroxy, alkoxy, carbonate, or bicarbonate.
- the carbonate base is lithium carbonate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or any combination thereof.
- the base is potassium hydroxide. In preferred embodiments, the base is sodium hydroxide.
- the base is dissolved in the solvent. In some embodiments, the base is dissolved in water. In some embodiments, the base contains water. In some embodiments, the base is dissolved in an organic solvent.
- the process is performed at a temperature below 50° C.
- the temperature is 20° C. to 40° C.
- the temeprature is 15-22° C.
- the temperature is 45° C., 40° C., 35° C., 30° C., 25° C., 20° C., 15° C., 10° C. In specific embodiment, the temperature is 30° C.
- the resulting precipitate material is a solid. In some embodiments, the resulting precipitate material is a paste.
- the resulting precipitate material is separated in step (b) by filtration. In some embodiments, the resulting precipitate material is separated in step (b) by centrifuge. In some embodiments, the resulting precipitate material is separated in step (b) by decantation.
- the subject invention also provides a method of obtaining the compound of formula (I)
- the subject invention also provides a compound (I)
- the subject invention also provides a compound (I)
- the salt of the compound (I) is a metal salt.
- the metal salt is a potassium salt.
- the subject invention also provides a composition comprising a compound (I), or a salt thereof.
- the salt of the compound (I) is a metal salt.
- the metal salt is a potassium salt.
- the composition further comprises a base.
- the base is potassium hydroxide.
- the subject invention also provides a composition comprising a precipitate and at least one solvent, wherein the precipitate comprises a salt of compound (I)
- the salt of the compound (I) is a metal salt.
- the metal salt is a potassium salt.
- the composition comprises at least two solvents. In some embodiments, the composition comprises at least three solvents. In some embodiments, the composition comprises at least four solvents.
- At least one of the solvents is a polar solvent.
- the polar solvent is an organic polar solvent.
- the organic polar solvent is dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), glycols, sulfolan, mono and di-glymes, acetamide, glycerine, ACN, nitro ethane or any combination thereof.
- the organic polar solvent is alcohol.
- the alcohol is methanol, ethanol or propanol. In preferred embodiments, the alcohol is ethanol.
- At least 1% of the total volume of the solvent is polar solvent.
- At least one of the solvents is a nonpolar solvent.
- the nonpolar solvent is an organic nonpolar solvent.
- the nonpolar solvent is nonpolar aromatic solvent.
- the nonpolar aromatic solvent is toluene, xylene, mono chloro benzene (MCB), naphtha, or any combination thereof.
- the nonpolar aromatic solvent is toluene.
- the naphtha is light naphtha. In some embodiments, the naphtha is heavy naphtha. In some embodiments, the naphtha is petroleum naphtha. In some embodiments, the solvent naphtha is the Solvesso® grades from ExxonMobil Chemical, especially Solvesso® 100 (CAS No. 64742-95-6), Solvesso® 150 (CAS No. 64742-94-5), and Solvesso® 200 (CAS No. 64742-94-5).
- none of the solvents is a nonpolar aromatic solvent.
- the nonpolar solvent is pentane, hexane, or dichloromethane (DCM).
- one of the solvents is water.
- the composition comprises one solvent wherein the solvent is ethanol.
- the composition comprises two solvents wherein the two solvents are toluene and ethanol.
- the composition comprises three solvents wherein the three solvents are toluene, water, and ethanol.
- the mixture was stirred at room temperature for 3 hours until all the KOH has disappeared (the color of the mixture was brown), and a brown solid was formed.
- the solid was filtered, washed with toluene (50 g) and dried at 30° C. under reduced pressure to afford phenoxy-K (hydrate) (306 g).
- the filtered solid comprised compound (I) and compound (II) in of ratio of 93:0.2.
- Example 5 Mother liquor from U.S. Pat. No. 4,046,798 Example 3 or Chinese Patent Application No. CN1363548A Example 5 (600 g) were evaporated under reduced pressure at room temperature to obtain about 300 g residue, which contains a mixture of 2-chloro-4-(trifluoromethyl)-phenol, i.e. compound (I), 2-chloro-5-(trifluoromethyl)-phenol, i.e. compound (II), and other impurities.
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Abstract
Description
- This application claims priority of U.S. Provisional Application No. 62/481,235, filed Apr. 4, 2017, the entire content of which is hereby incorporated by reference herein.
- Throughout this application various publications are referenced. The disclosures of these documents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
- The present subject matter relates to a process for separating compound (I) from a mixture comprising compound (I). The present subject matter also relates to a process for separating compound (I) from a mixture comprising compound (I) and compound (II).
- 2-Chloro-4-trifluoromethyl-phenol (compound (I)) is used as a reagent in the manufacture of certain nitro diphenyl ether herbicide.
- Many active ingredients, in different fields such as pharma and agriculture, use compound (I) in their synthetic pathways.
- Compound (I) is often used as a starting material.
- Compound (I) can be obtained as a by-product and/or residual waste in different manufacturing process such as described in U.S. Pat. No. 4,046,798.
- In the residual waste, the compound (I) may exist in a mixture with 2-chloro-5-(trifluoromethyl)-phenol (compound (II)).
- The residual waste also may comprise unknown impurities.
- In manufacturing processes, impurities can react in parallel synthetic pathways, creating a need for extra further purification steps leading to additional costs. In addition, undesirable side-reactions require an excess of reagents, decrease yields, and increase costs and waste.
- Several known procedures such as crystallization, column separation and distillation described in the literature may be used for purifying and isolating specific compound from mixtures or for recycling and converting synthesis mother liquors into reusable material.
- For example, U.S. Pat. No. 2,016,848 discloses a method of seperating orto and para benzyl phenol isomers via converting the compounds to their salt form and filtrating for one of the isomers. In another example, U.S. Pat. No. 4,366,329 discloses a method of seperating meta and para bromo phenol isomers via sodium salt derivative.
- Separation of compounds depends on the specific structure of the compound to be isolated. The position and location of the functional groups influence the separation method and conditions.
- Compounds, such as compound (I), which have multi-functional group wherein at least one of the groups is tri-fluoro methyl are very sensitive and can rapidly undergo hydrolysis, resulting with carboxylic acid. The phenol is sensitive to water in alkali conditions and the Cl moiety can react with a phenol of another molecule.
- Each of the separation methods currently known in the art has disadvantages and cannot be used for separating compound (I) from a mixture. Distillation of the mixture causes high corrosion and is accompanied with decomposition of the desirable compound.
- Column separation has a very high cost and is a cumbersome procedure. Column separation also requires use of multiple and large amounts of solvents. Conventional isomer separation cannot be used due the multi-functional groups and the type and nature of the functional groups.
- There is a need to find an easy, inexpensive procedure to isolate 2-Chloro-4-trifluoromethyl-phenol, i.e. compound (I), from a mixture of isomers and other impurities.
- There is also a need to find a method for obtaining 2-Chloro-4-trifluoromethyl-phenol, i.e. compound (I), in high yield, in an easy, low cost, and high selectivity and purity.
- It was found that compound (I) can be isolated and purified without the need for distillation and/or separation by column chromatography.
- The present invention provides a process for separating compound (I), or a salt thereof, from a mixture comprising the compound (I),
-
- the process comprising the steps of:
- (a) combining the mixture with an amount of a base in the presence of at least one solvent so as to form a precipitate; and
- (b) separating the precipitate,
thereby separating the compound (I) from the mixture.
- Prior to setting forth the present subject matter in detail, it may be helpful to provide definitions of certain terms to be used herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this subject matter pertains.
- The term “a” or “an” as used herein includes the singular and the plural, unless specifically stated otherwise. Therefore, the terms “a,” “an,” or “at least one” can be used interchangeably in this application.
- Throughout the application, descriptions of various embodiments use the term “comprising”; however, it will be understood by one of skill in the art, that in some specific instances, an embodiment can alternatively be described using the language “consisting essentially of” or “consisting of”. In each such instance, the terms “comprising,” “consisting essentially of,” and “consisting of” are intended to have the same meaning as each such term would have when used as the transition phrase of a patent claim.
- As used herein, the term “about” specifically includes ±10% from the indicated values in the range. In addition, the endpoints of all ranges directed to the same component or property herein are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges.
- The present invention provides a process for separating compound (I), or a salt thereof, from a mixture comprising the compound (I),
-
- the process comprising the steps of:
- (a) combining the mixture with an amount of a base in the presence of at least one solvent so as to form a precipitate; and
- (b) separating the precipitate,
thereby separating the compound (I) from the mixture.
- In some embodiments, the mixture further comprises compound (II)
- The process described herein may be used to separate compound (I) from mixtures with any compound (I) to compound (II) ratio.
- In some embodiment, the ratio of compound (I) to compound (II) in the mixture is from 1:1000 to 1000:1.
- In some embodiment, the ratio of compound (I) to compound (II) in the mixture is from 90:10 to 70:30. In some embodiments, the ratio of compound (I) to compound (II) in the mixture is 90:10, 85:15, or 80:20, 75:25, or 70:30.
- In some embodiments, the ratio of compound (I) to compound (II) in the mixture is 88:11.
- In some embodiments, the mixture which comprises compound (I) and compound (II) is a solution.
- In some embodiment, the concentration of the compound (I) in the solution is from about 1% to 99%.
- In some embodiments, the resulting precipitate material is a metal salt.
- In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 1000:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 500:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 200:1. In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is from 50:1 to 100:1.
- In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is 77:0.4.
- In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is 98.15:1.85.
- In some embodiments, the ratio of compound (I) to compound (II) in the resulting precipitate material is 93:0.2.
- In some embodiment, the purity of compound (I) in the resulting precipitate material is 80% or more, 85% or more, 90% or more, 95% or more, or 99% or more. In some embodiment, the purity of compound (I) in the resulting precipitate material is 80%, 85%, 90%, 95%, or 99%.
- In some embodiment, the purity of compound (I) in the resulting precipitate material is 93%.
- In some embodiment, the process further comprises neutralization of the metal salt with an acid. In some embodiment, the metal salt of compound (I) is neutralized with an acid.
- In some embodiments, the acid is an organic acid.
- Organic acids that may be used include but are not limited to carboxylic acids such as citric acid, fumaric acid, phthalic acid, maleic acid, malic acid, oxalic acid, adipic acid, glutaric acid, 2-methyl glutaric acid, succinic acid and tartaric acid, tri fluoro methyl acetic acid, p-toluene sulfonic acid or any combination thereof.
- In some embodiments, the acid is an inorganic acid.
- Inorganic acids that may be used include but are not limited to hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, persulfuric acid or any combination thereof.
- In some embodiments, the mixture reacts with the base in the presence of at least two solvents.
- In some embodiments, the mixture reacts with the base in the presence of at least three solvents.
- In some embodiments, the mixture reacts with the base in the presence of at least four solvents.
- In some embodiments, at least one of the solvents is a polar solvent. In some embodiments, the polar solvent is an organic polar solvent.
- In some embodiments, the organic polar solvent is dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), glycols, sulfolan, mono and di-glymes, acetamide, glycerine, ACN, nitro ethane or any combination thereof.
- In some embodiments, the organic polar solvent is an alcohol. In some embodiments, the alcohol is methanol, ethanol or propanol. In preferred embodiments, the alcohol is ethanol.
- In some embodiments, at least 1% of the total volume of the solvent is polar solvent.
- In some embodiments, at least one of the solvents is a nonpolar solvent. In some embodiments, the nonpolar solvent is an organic nonpolar solvent.
- In some embodiments, the nonpolar solvent is nonpolar aromatic solvent. In some embodiments, the nonpolar aromatic solvent is toluene, xylene, mono chloro benzene (MCB), naphtha, or any combination thereof. In preferred embodiments, the nonpolar aromatic solvent is toluene.
- In some embodiments, the naphtha is light naphtha. In some embodiments, the naphtha is heavy naphtha. In some embodiments, the naphtha is petroleum naphtha. In some embodiments, the solvent naphtha is the Solvesso® grades from ExxonMobil Chemical, especially Solvesso® 100 (CAS No. 64742-95-6), Solvesso® 150 (CAS No. 64742-94-5), and Solvesso® 200 (CAS No. 64742-94-5).
- In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 100° F. to about 200° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 100° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 150° F. In some embodiments, the nonpolar aromatic solvent has a flashpoint of about 200° F.
- In some embodiments, none of the solvents is a nonpolar aromatic solvent.
- In some embodiment, the nonpolar solvent is pentane, hexane, or dichloromethane (DCM).
- In some embodiments, one of the solvents is water. In some embodiments, the water is added to the reaction mixture. In some embodiments, the water is formed during the reaction. In some embodiments, the water is formed with addition of the base into the reaction mixture.
- In some embodiments, at least 1% of the total volume of the solvent is water.
- In some embodiments, the mixture is solution. In some embodiments, the mixture is solid.
- In some embodiments, the concentration of water in the aqueous solution is not more than 25%. In some embodiments, the concentration of water in the aqueous solution is 10%. In some embodiments, the concentration of water in the aqueous solution is 1%.
- In some embodiments, the mixture reacts with the base in the presence of one solvent wherein the solvent is ethanol. In some embodiments, the mixture reacts with the base in the presence of at least one solvent wherein one of the solvent is ethanol.
- In some embodiments, the mixture reacts with the base in the presence of two solvents wherein the two solvents are toluene and ethanol. In some embodiments, the mixture reacts with the base in the presence of at least two solvents and two of the solvents are toluene and ethanol.
- In some embodiments, the mixture reacts with the base in the presence of three solvents wherein the three solvents are toluene, water, and ethanol. In some embodiments, the mixture reacts with the base in the presence of at least three solvents and three of the at least three solvents are toluene, water, and ethanol.
- In some embodiments, the base is an organic base. In some embodiments, the base is an inorganic base.
- In some embodiments, the base is an alkali metal base. In some embodiments, the base is an earth alkaline metal base. In some embodiments, the alkaline metal is sodium, lithium, or potassium. In some embodiments, the earth alkaline metal is magnesium or calcium.
- In some embodiments, the organic base is triethylamine, trimethylamine, ammonia, ammonium hydroxide, pyridine, guanidines, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, or 1,4-diazabicyclo[2.2.2]octane (DABCO).
- In some embodiments, the inorganic base is hydroxy, alkoxy, carbonate, or bicarbonate.
- In some embodiments, the carbonate base is lithium carbonate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or any combination thereof.
- In preferred embodiments, the base is potassium hydroxide. In preferred embodiments, the base is sodium hydroxide.
- In some embodiments, the base is dissolved in the solvent. In some embodiments, the base is dissolved in water. In some embodiments, the base contains water. In some embodiments, the base is dissolved in an organic solvent.
- In some embodiments, the process is performed at a temperature below 50° C. In some embodiments, the temperature is 20° C. to 40° C. In some embodiments, the temeprature is 15-22° C. In some embodiments, the temperature is 45° C., 40° C., 35° C., 30° C., 25° C., 20° C., 15° C., 10° C. In specific embodiment, the temperature is 30° C.
- In some embodiments, the resulting precipitate material is a solid. In some embodiments, the resulting precipitate material is a paste.
- In some embodiments, the resulting precipitate material is separated in step (b) by filtration. In some embodiments, the resulting precipitate material is separated in step (b) by centrifuge. In some embodiments, the resulting precipitate material is separated in step (b) by decantation.
- The subject invention also provides a method of obtaining the compound of formula (I)
- comprising separating the compound of formula (I) according to any embodiments of the present invention.
- The subject invention also provides a compound (I)
- or a salt thereof,
separated using the process described herein. - The subject invention also provides a compound (I)
- or a salt thereof.
- In some embodiments, the salt of the compound (I) is a metal salt.
- In some embodiments, the metal salt is a potassium salt.
- The subject invention also provides a composition comprising a compound (I), or a salt thereof.
- In some embodiments, the salt of the compound (I) is a metal salt.
- In some embodiments, the metal salt is a potassium salt.
- In some embodiments, the composition further comprises a base.
- In some embodiments, the base is potassium hydroxide.
- The subject invention also provides a composition comprising a precipitate and at least one solvent, wherein the precipitate comprises a salt of compound (I)
- In some embodiments, the salt of the compound (I) is a metal salt.
- In some embodiments, the metal salt is a potassium salt.
- In some embodiments, the composition comprises at least two solvents. In some embodiments, the composition comprises at least three solvents. In some embodiments, the composition comprises at least four solvents.
- In some embodiments, at least one of the solvents is a polar solvent. In some embodiments, the polar solvent is an organic polar solvent.
- In some embodiments, the organic polar solvent is dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), glycols, sulfolan, mono and di-glymes, acetamide, glycerine, ACN, nitro ethane or any combination thereof.
- In some embodiments, the organic polar solvent is alcohol. In some embodiments, the alcohol is methanol, ethanol or propanol. In preferred embodiments, the alcohol is ethanol.
- In some embodiments, at least 1% of the total volume of the solvent is polar solvent.
- In some embodiments, at least one of the solvents is a nonpolar solvent. In some embodiments, the nonpolar solvent is an organic nonpolar solvent.
- In some embodiments, the nonpolar solvent is nonpolar aromatic solvent. In some embodiments, the nonpolar aromatic solvent is toluene, xylene, mono chloro benzene (MCB), naphtha, or any combination thereof. In preferred embodiment, the nonpolar aromatic solvent is toluene.
- In some embodiments, the naphtha is light naphtha. In some embodiments, the naphtha is heavy naphtha. In some embodiments, the naphtha is petroleum naphtha. In some embodiments, the solvent naphtha is the Solvesso® grades from ExxonMobil Chemical, especially Solvesso® 100 (CAS No. 64742-95-6), Solvesso® 150 (CAS No. 64742-94-5), and Solvesso® 200 (CAS No. 64742-94-5).
- In some embodiments, none of the solvents is a nonpolar aromatic solvent.
- In some embodiment, the nonpolar solvent is pentane, hexane, or dichloromethane (DCM).
- In some embodiments, one of the solvents is water.
- In some embodiments, the composition comprises one solvent wherein the solvent is ethanol.
- In some embodiments, the composition comprises two solvents wherein the two solvents are toluene and ethanol.
- In some embodiments, the composition comprises three solvents wherein the three solvents are toluene, water, and ethanol.
- Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the invention.
- This invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative of the invention as described more fully in the claims which follow thereafter.
- The invention is illustrated by the following examples without limiting it thereby.
- Into a three neck round bottom flask equipped with a mechanical stirrer, dropping funnel and thermometer were added toluene (350 g), ethanol (25 g), water (15 g) and potassium hydroxide flakes (90 g). The mixture was stirred at room temperature for 1 hour. A mixture (300 g, 1.53 mol of phenols mixture) of 2-chloro-4-(trifluoromethyl)-phenol, i.e. compound (I), and 2-chloro-5-(trifluoromethyl)-phenol, i.e. compound (II), was added dropwise, during 45 minutes, at such a rate that the temperature maintained at 15-22° C. The mixture was stirred at room temperature for 3 hours until all the KOH has disappeared (the color of the mixture was brown), and a brown solid was formed. The solid was filtered, washed with toluene (50 g) and dried at 30° C. under reduced pressure to afford phenoxy-K (hydrate) (306 g). The filtered solid comprised compound (I) and compound (II) in of ratio of 93:0.2.
- Mother liquor from U.S. Pat. No. 4,046,798 Example 3 or Chinese Patent Application No. CN1363548A Example 5 (600 g) were evaporated under reduced pressure at room temperature to obtain about 300 g residue, which contains a mixture of 2-chloro-4-(trifluoromethyl)-phenol, i.e. compound (I), 2-chloro-5-(trifluoromethyl)-phenol, i.e. compound (II), and other impurities.
- Into a three neck round bottom flask equipped with a mechanical stirrer, dropping funnel and thermometer were added toluene (350 g), ethanol (25 g), water (15 g) and potassium hydroxide flakes (90 g). The mixture was stirred at room temperature for 1 hour and then the above residue left from the mother liquor evaporation (300 g) was added dropwise, during 45 minutes, at such a rate that the temperature maintained at 15-22° C. The mixture was stirred at room temperature for 3 hours until all the KOH has disappeared (the color of the mixture was brown), and a brown solid was formed. The solid was filtered, washed with toluene (50 g) and dried at 30° C. under reduced pressure to afford phenoxy-K (hydrate) (306 g) (ratio of compound (I) to compound (II) was 93:0.2).
- Into a three neck round bottom flask equipped with a mechanical stirrer, dropping funnel and thermometer were added ethanol (150 g) and potassium hydroxide flakes (32 g). The mixture was stirred at room temperature for 1 hour and then a mixture (100 g) of 2-chloro-4-(trifluoromethyl)-phenol, i.e. compound (I) and 2-chloro-5-(trifluoromethyl)-phenol, i.e. compound (II), were added dropwise, during 45 minutes, at such a rate that the temperature maintained at 15-20° C. The ratio of compound (I) to compound (II) in the mixture was 95:5. The mixture was stirred at room temperature for 18 hours. No solid was formed. Ethanol was distilled out until a precipitation was observed. The solid was filtered and dried at 30° C. under reduced pressure to afford phenoxy-K (hydrate) (18.8 g) (ratio of compound (I) to compound (II) was 98.15:1.85).
-
- 1. U.S. Pat. No. 2,016,848, issued Oct. 8, 1935 (Akimoff et al.).
- 2. U.S. Pat. No. 4,366,329, issued Dec. 28, 1982 (Raynolds et al.).
Claims (26)
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US17/526,316 US20220073442A1 (en) | 2017-04-04 | 2021-11-15 | Separation of phenol isomer |
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PCT/IB2018/000446 WO2018185559A1 (en) | 2017-04-04 | 2018-04-03 | Separation of phenol isomer |
US201916500271A | 2019-10-02 | 2019-10-02 | |
US17/526,316 US20220073442A1 (en) | 2017-04-04 | 2021-11-15 | Separation of phenol isomer |
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US16/500,271 Continuation US11203562B2 (en) | 2017-04-04 | 2018-04-03 | Separation of phenol isomer |
PCT/IB2018/000446 Continuation WO2018185559A1 (en) | 2017-04-04 | 2018-04-03 | Separation of phenol isomer |
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US17/526,316 Abandoned US20220073442A1 (en) | 2017-04-04 | 2021-11-15 | Separation of phenol isomer |
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EP (1) | EP3606897B1 (en) |
CN (2) | CN117924039A (en) |
BR (1) | BR112019017945A2 (en) |
IL (1) | IL269824B (en) |
WO (1) | WO2018185559A1 (en) |
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EP3606897B1 (en) | 2017-04-04 | 2024-02-28 | Adama Agan Ltd. | Separation of phenol isomer |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304531A (en) * | 1979-05-16 | 1994-04-19 | Basf Corp | Nitrodiphenyl ether herbicides |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2016848A (en) | 1934-05-07 | 1935-10-08 | Monsanto Chemicals | Method of separating phenolic isomers |
DE2016624A1 (en) | 1970-04-08 | 1971-10-21 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Microbicidal agents |
US4046798A (en) | 1973-02-12 | 1977-09-06 | Rohm And Haas Company | Herbicidal 4-trifluoromethyl-4'nitrodiphenyl ethers |
US4262152A (en) * | 1979-05-02 | 1981-04-14 | Rohm And Haas Company | Preparation of trifluoromethylphenyl nitrophenylethers |
US4366329A (en) | 1981-06-22 | 1982-12-28 | Eastman Kodak Company | Process for the separation of meta and para isomers of the sodium salt of bromophenol |
FR2529197A1 (en) | 1982-06-29 | 1983-12-30 | Rhone Poulenc Agrochimie | PROCESS FOR THE PREPARATION OF PHENATES SUBSTITUTED BY HALOGEN GROUPS OR CORRESPONDING PHENOLS |
CN1363548A (en) | 2001-01-20 | 2002-08-14 | 浙江巨化股份有限公司兰溪农药厂 | Bietherifying process for synthesizing oxyfluorfen |
WO2007120012A1 (en) | 2006-04-19 | 2007-10-25 | Amorepacific Corporation | Novel compounds, isomer thereof, or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist; and pharmaceutical compositions containing the same |
EP3606897B1 (en) | 2017-04-04 | 2024-02-28 | Adama Agan Ltd. | Separation of phenol isomer |
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2018
- 2018-04-03 EP EP18727419.6A patent/EP3606897B1/en active Active
- 2018-04-03 US US16/500,271 patent/US11203562B2/en active Active
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- 2018-04-03 WO PCT/IB2018/000446 patent/WO2018185559A1/en unknown
- 2018-04-03 CN CN201880022177.8A patent/CN110573483B/en active Active
- 2018-04-03 BR BR112019017945A patent/BR112019017945A2/en not_active Application Discontinuation
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2019
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2021
- 2021-11-15 US US17/526,316 patent/US20220073442A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304531A (en) * | 1979-05-16 | 1994-04-19 | Basf Corp | Nitrodiphenyl ether herbicides |
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EP3606897A1 (en) | 2020-02-12 |
IL269824A (en) | 2019-11-28 |
BR112019017945A2 (en) | 2020-05-19 |
CN110573483B (en) | 2023-12-29 |
US20210101857A1 (en) | 2021-04-08 |
CN117924039A (en) | 2024-04-26 |
CN110573483A (en) | 2019-12-13 |
IL269824B (en) | 2022-05-01 |
WO2018185559A1 (en) | 2018-10-11 |
US11203562B2 (en) | 2021-12-21 |
EP3606897B1 (en) | 2024-02-28 |
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