US20200255457A1 - Process for the removal and return of a catalyst to a liquid phase medium - Google Patents
Process for the removal and return of a catalyst to a liquid phase medium Download PDFInfo
- Publication number
- US20200255457A1 US20200255457A1 US16/707,816 US201916707816A US2020255457A1 US 20200255457 A1 US20200255457 A1 US 20200255457A1 US 201916707816 A US201916707816 A US 201916707816A US 2020255457 A1 US2020255457 A1 US 2020255457A1
- Authority
- US
- United States
- Prior art keywords
- group
- catalyst
- formula
- compound
- reaction
- 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
- 239000003054 catalyst Substances 0.000 title claims abstract description 133
- 238000000034 method Methods 0.000 title claims abstract description 55
- 230000008569 process Effects 0.000 title claims abstract description 29
- 239000007791 liquid phase Substances 0.000 title abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 89
- 239000012429 reaction media Substances 0.000 claims abstract description 55
- 125000003118 aryl group Chemical group 0.000 claims abstract description 38
- 125000001424 substituent group Chemical group 0.000 claims abstract description 23
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 18
- 125000005647 linker group Chemical group 0.000 claims abstract description 18
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- 150000002825 nitriles Chemical class 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 6
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims abstract description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims abstract description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 107
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 239000000377 silicon dioxide Substances 0.000 claims description 52
- 229910052751 metal Inorganic materials 0.000 claims description 42
- 239000002184 metal Substances 0.000 claims description 41
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 23
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 23
- 239000003446 ligand Substances 0.000 claims description 21
- 229910052763 palladium Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000002524 organometallic group Chemical group 0.000 claims description 17
- 229920000642 polymer Polymers 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 229910052742 iron Inorganic materials 0.000 claims description 14
- 229910052759 nickel Inorganic materials 0.000 claims description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 14
- 239000007795 chemical reaction product Substances 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000002577 pseudohalo group Chemical group 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 229910052802 copper Inorganic materials 0.000 claims description 10
- 239000010949 copper Substances 0.000 claims description 10
- 229910052741 iridium Inorganic materials 0.000 claims description 9
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 9
- 229910052703 rhodium Inorganic materials 0.000 claims description 9
- 239000010948 rhodium Substances 0.000 claims description 9
- 229910052707 ruthenium Inorganic materials 0.000 claims description 9
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052697 platinum Inorganic materials 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
- 229920002554 vinyl polymer Polymers 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052796 boron Inorganic materials 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 6
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052710 silicon Inorganic materials 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 238000004132 cross linking Methods 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052747 lanthanoid Inorganic materials 0.000 claims description 3
- 150000002602 lanthanoids Chemical class 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 229910052726 zirconium Inorganic materials 0.000 claims description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 150000003462 sulfoxides Chemical class 0.000 claims description 2
- 125000004799 bromophenyl group Chemical group 0.000 claims 2
- -1 triflate Chemical compound 0.000 abstract description 25
- 239000002815 homogeneous catalyst Substances 0.000 abstract description 6
- 238000006069 Suzuki reaction reaction Methods 0.000 abstract description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 abstract description 4
- 238000006880 cross-coupling reaction Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000004519 manufacturing process Methods 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 125000000524 functional group Chemical group 0.000 description 16
- 238000001816 cooling Methods 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 238000011068 loading method Methods 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 150000002739 metals Chemical class 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229910016455 AlBN Inorganic materials 0.000 description 8
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- 229920001296 polysiloxane Polymers 0.000 description 8
- 238000011084 recovery Methods 0.000 description 8
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 8
- NKSJNEHGWDZZQF-UHFFFAOYSA-N ethenyl(trimethoxy)silane Chemical compound CO[Si](OC)(OC)C=C NKSJNEHGWDZZQF-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 239000005864 Sulphur Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- OXYZDRAJMHGSMW-UHFFFAOYSA-N 3-chloropropyl(trimethoxy)silane Chemical compound CO[Si](OC)(OC)CCCCl OXYZDRAJMHGSMW-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ACXRRQPYVGRNTI-IOPABZIGSA-N C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)CC=C2.C1=CC2=C(C=C1)CC=C2.C1=CC2=CC=CC2C=C1.C1=CC2=CCC=C2C=C1.C1=CC2=CCC=C2C=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2[K]C=CC2=C1.C1=CC=C2[K]C=CC2=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CCC=C1.C1=CC[K]=C1.C1=C[K]=CC1.C1=C[K]=[K]C1.C1=C[K]C=C1 Chemical compound C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)C1=C(/C=C\C=C/1)C2.C1=CC2=C(C=C1)CC=C2.C1=CC2=C(C=C1)CC=C2.C1=CC2=CC=CC2C=C1.C1=CC2=CCC=C2C=C1.C1=CC2=CCC=C2C=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2C=CC=CC2=C1.C1=CC=C2[K]C=CC2=C1.C1=CC=C2[K]C=CC2=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CC=CC=C1.C1=CCC=C1.C1=CC[K]=C1.C1=C[K]=CC1.C1=C[K]=[K]C1.C1=C[K]C=C1 ACXRRQPYVGRNTI-IOPABZIGSA-N 0.000 description 4
- CGVNZOPEXUWQFV-UHFFFAOYSA-N O=C1CC(=O)C2=C1C=CC=C2.O=S1(=O)CCC2=CC=CC=C2O1 Chemical compound O=C1CC(=O)C2=C1C=CC=C2.O=S1(=O)CCC2=CC=CC=C2O1 CGVNZOPEXUWQFV-UHFFFAOYSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 4
- 238000007172 homogeneous catalysis Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000011369 resultant mixture Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 3
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 3
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 238000005810 carbonylation reaction Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000006266 etherification reaction Methods 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- YUQUNWNSQDULTI-UHFFFAOYSA-N 2-bromobenzenethiol Chemical compound SC1=CC=CC=C1Br YUQUNWNSQDULTI-UHFFFAOYSA-N 0.000 description 2
- HNGQQUDFJDROPY-UHFFFAOYSA-N 3-bromobenzenethiol Chemical compound SC1=CC=CC(Br)=C1 HNGQQUDFJDROPY-UHFFFAOYSA-N 0.000 description 2
- SJECZPVISLOESU-UHFFFAOYSA-N 3-trimethoxysilylpropan-1-amine Chemical compound CO[Si](OC)(OC)CCCN SJECZPVISLOESU-UHFFFAOYSA-N 0.000 description 2
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 2
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- QSUXNVNNPIUCAH-UHFFFAOYSA-N CCCCNC(=O)C1=CC=C(Br)C=C1 Chemical compound CCCCNC(=O)C1=CC=C(Br)C=C1 QSUXNVNNPIUCAH-UHFFFAOYSA-N 0.000 description 2
- 238000007341 Heck reaction Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- CURBUOKDMKNARG-UHFFFAOYSA-N O=C(c1ccccc11)[IH]C1=O Chemical compound O=C(c1ccccc11)[IH]C1=O CURBUOKDMKNARG-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000005347 biaryls Chemical group 0.000 description 2
- 238000006795 borylation reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000007333 cyanation reaction Methods 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- UGEQUCUBWNAUJS-UHFFFAOYSA-N (3-bromophenyl)methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC(Br)=C1 UGEQUCUBWNAUJS-UHFFFAOYSA-N 0.000 description 1
- BRXDAEMGSYZHGK-UHFFFAOYSA-N (4-bromophenyl)-trimethoxysilane Chemical compound CO[Si](OC)(OC)C1=CC=C(Br)C=C1 BRXDAEMGSYZHGK-UHFFFAOYSA-N 0.000 description 1
- NDTIXHNCNLKURN-UHFFFAOYSA-N (4-nitrophenyl) trifluoromethanesulfonate Chemical compound [O-][N+](=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 NDTIXHNCNLKURN-UHFFFAOYSA-N 0.000 description 1
- VAIMIWMAVGWBGX-UHFFFAOYSA-N 1-bromo-2-(2-bromophenyl)sulfanylbenzene Chemical compound BrC1=CC=CC=C1SC1=CC=CC=C1Br VAIMIWMAVGWBGX-UHFFFAOYSA-N 0.000 description 1
- QIWRAJMIEDRYNM-UHFFFAOYSA-N 1-bromo-3-(3-bromophenyl)sulfanylbenzene Chemical compound BrC1=CC=CC(SC=2C=C(Br)C=CC=2)=C1 QIWRAJMIEDRYNM-UHFFFAOYSA-N 0.000 description 1
- CLPVCAXOQZIJGW-UHFFFAOYSA-N 1-bromo-4-(4-bromophenyl)sulfanylbenzene Chemical compound C1=CC(Br)=CC=C1SC1=CC=C(Br)C=C1 CLPVCAXOQZIJGW-UHFFFAOYSA-N 0.000 description 1
- QJMIKDAPJKCCHL-UHFFFAOYSA-N 1-bromo-4-(4-bromophenyl)sulfinylbenzene Chemical compound C1=CC(Br)=CC=C1S(=O)C1=CC=C(Br)C=C1 QJMIKDAPJKCCHL-UHFFFAOYSA-N 0.000 description 1
- QBNABJXQGRVIRA-UHFFFAOYSA-N 1-bromo-4-(4-bromophenyl)sulfonylbenzene Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)C1=CC=C(Br)C=C1 QBNABJXQGRVIRA-UHFFFAOYSA-N 0.000 description 1
- MJEPOVIWHVRBIT-UHFFFAOYSA-N 1-chloro-4-(4-chlorophenyl)sulfanylbenzene Chemical compound C1=CC(Cl)=CC=C1SC1=CC=C(Cl)C=C1 MJEPOVIWHVRBIT-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- AYVPVDWQZAAZCM-UHFFFAOYSA-N 4-bromo-n-methylaniline Chemical compound CNC1=CC=C(Br)C=C1 AYVPVDWQZAAZCM-UHFFFAOYSA-N 0.000 description 1
- TUXYZHVUPGXXQG-UHFFFAOYSA-M 4-bromobenzoate Chemical compound [O-]C(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-M 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910018626 Al(OH) Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101150030352 Arsi gene Proteins 0.000 description 1
- 229910015444 B(OH)3 Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
- SVHYADBHUWYBAG-UHFFFAOYSA-N C1(CCC(N1SCC1=CC(=CC=C1)Br)=O)=O Chemical compound C1(CCC(N1SCC1=CC(=CC=C1)Br)=O)=O SVHYADBHUWYBAG-UHFFFAOYSA-N 0.000 description 1
- UWFUSSAVZJGTOA-UHFFFAOYSA-N CBr.CCCCN1C(=O)C2=C(C=CC=C2)C1=O Chemical compound CBr.CCCCN1C(=O)C2=C(C=CC=C2)C1=O UWFUSSAVZJGTOA-UHFFFAOYSA-N 0.000 description 1
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N CC1=CC=C(Br)C=C1 Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 1
- CGXJQSNNMFCQCB-UHFFFAOYSA-N CCCC.CCCSC1=CC=C(Br)C=C1 Chemical compound CCCC.CCCSC1=CC=C(Br)C=C1 CGXJQSNNMFCQCB-UHFFFAOYSA-N 0.000 description 1
- NUPWGLKBGVNSJX-UHFFFAOYSA-N CCCC1=CC=C(Br)C=C1 Chemical compound CCCC1=CC=C(Br)C=C1 NUPWGLKBGVNSJX-UHFFFAOYSA-N 0.000 description 1
- GRGCSRZFEGIWOM-UHFFFAOYSA-N CCCCN(C)C1=CC=C(Br)C=C1 Chemical compound CCCCN(C)C1=CC=C(Br)C=C1 GRGCSRZFEGIWOM-UHFFFAOYSA-N 0.000 description 1
- UYYQEEHMBSWTFO-UHFFFAOYSA-N CCCCOC(=O)C1=CC=C(Br)C=C1 Chemical compound CCCCOC(=O)C1=CC=C(Br)C=C1 UYYQEEHMBSWTFO-UHFFFAOYSA-N 0.000 description 1
- BOUVKHWPQNEXTO-UHFFFAOYSA-N CCCCOC1=CC=C(Br)C=C1 Chemical compound CCCCOC1=CC=C(Br)C=C1 BOUVKHWPQNEXTO-UHFFFAOYSA-N 0.000 description 1
- VPDIDTOQESQQSN-HVVIIGHZSA-N CCCONC.CN/C=C/N=N Chemical compound CCCONC.CN/C=C/N=N VPDIDTOQESQQSN-HVVIIGHZSA-N 0.000 description 1
- ILRRBENNUDNIJR-UHFFFAOYSA-N CCCS(=O)(=O)C1=CC=C(Br)C=C1 Chemical compound CCCS(=O)(=O)C1=CC=C(Br)C=C1 ILRRBENNUDNIJR-UHFFFAOYSA-N 0.000 description 1
- QRKXEVISLSWOTB-UHFFFAOYSA-N CCCS(=O)C1=CC=C(Br)C=C1 Chemical compound CCCS(=O)C1=CC=C(Br)C=C1 QRKXEVISLSWOTB-UHFFFAOYSA-N 0.000 description 1
- CCYFUGBAHQQLQN-UHFFFAOYSA-N CCCSC1=C(Br)C=CC=C1 Chemical compound CCCSC1=C(Br)C=CC=C1 CCYFUGBAHQQLQN-UHFFFAOYSA-N 0.000 description 1
- XLTBVGAEUXNUNJ-UHFFFAOYSA-N CCCSC1=CC=C(Br)C=C1 Chemical compound CCCSC1=CC=C(Br)C=C1 XLTBVGAEUXNUNJ-UHFFFAOYSA-N 0.000 description 1
- UIVFJAFRNBDAEM-UHFFFAOYSA-N CCCSC1=CC=C(Cl)C=C1 Chemical compound CCCSC1=CC=C(Cl)C=C1 UIVFJAFRNBDAEM-UHFFFAOYSA-N 0.000 description 1
- NSMMNPTUCQUBHB-UHFFFAOYSA-N CCCSC1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 Chemical compound CCCSC1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 NSMMNPTUCQUBHB-UHFFFAOYSA-N 0.000 description 1
- QARXAUVHMLYHJH-UHFFFAOYSA-N CCCSC1=CC=CC(Br)=C1 Chemical compound CCCSC1=CC=CC(Br)=C1 QARXAUVHMLYHJH-UHFFFAOYSA-N 0.000 description 1
- ARWFCJTWHPMBQI-UHFFFAOYSA-N CCCSC1CC(=O)N(CC2=CC=CC(Br)=C2)C1=O Chemical compound CCCSC1CC(=O)N(CC2=CC=CC(Br)=C2)C1=O ARWFCJTWHPMBQI-UHFFFAOYSA-N 0.000 description 1
- BKGHGKBUNJGNMZ-UHFFFAOYSA-N CCCSCCNC(=O)C1=CC=C(Br)C=C1 Chemical compound CCCSCCNC(=O)C1=CC=C(Br)C=C1 BKGHGKBUNJGNMZ-UHFFFAOYSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 238000006639 Goldberg reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 238000006716 Hiyama reaction Methods 0.000 description 1
- 0 NCC(C1)(*1C1)c(cccc2)c2OS1(=O)=O Chemical compound NCC(C1)(*1C1)c(cccc2)c2OS1(=O)=O 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- JAABVJXDGCSIJX-UHFFFAOYSA-N O=C(c(cc1)ccc1Br)NCCSCCC1CCCCCCCC1 Chemical compound O=C(c(cc1)ccc1Br)NCCSCCC1CCCCCCCC1 JAABVJXDGCSIJX-UHFFFAOYSA-N 0.000 description 1
- OLKAWWUNAJQFQL-UHFFFAOYSA-N O=S1(Oc2ccccc2C(C2)(CC3)C23C1)=O Chemical compound O=S1(Oc2ccccc2C(C2)(CC3)C23C1)=O OLKAWWUNAJQFQL-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 238000006579 Tsuji-Trost allylation reaction Methods 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- QUWAWKOUPYMZJS-UHFFFAOYSA-N butanedioic acid ethylsulfanylethane Chemical compound C(C)SCC.C(CCC(=O)O)(=O)O QUWAWKOUPYMZJS-UHFFFAOYSA-N 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000007819 coupling partner Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000003106 haloaryl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 238000007210 heterogeneous catalysis Methods 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 238000007037 hydroformylation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910000765 intermetallic Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- NJRXVEJTAYWCQJ-UHFFFAOYSA-N thiomalic acid Chemical compound OC(=O)CC(S)C(O)=O NJRXVEJTAYWCQJ-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- UBMUZYGBAGFCDF-UHFFFAOYSA-N trimethoxy(2-phenylethyl)silane Chemical compound CO[Si](OC)(OC)CCC1=CC=CC=C1 UBMUZYGBAGFCDF-UHFFFAOYSA-N 0.000 description 1
- HQYALQRYBUJWDH-UHFFFAOYSA-N trimethoxy(propyl)silane Chemical compound CCC[Si](OC)(OC)OC HQYALQRYBUJWDH-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
- C08G77/382—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon
- C08G77/385—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing halogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/22—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen
- C08G77/28—Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen sulfur-containing groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
- B01J31/069—Hybrid organic-inorganic polymers, e.g. silica derivatized with organic groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/1616—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts
- B01J31/1625—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups
- B01J31/1633—Coordination complexes, e.g. organometallic complexes, immobilised on an inorganic support, e.g. ship-in-a-bottle type catalysts immobilised by covalent linkages, i.e. pendant complexes with optional linking groups covalent linkages via silicon containing groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/165—Polymer immobilised coordination complexes, e.g. organometallic complexes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/165—Polymer immobilised coordination complexes, e.g. organometallic complexes
- B01J31/1658—Polymer immobilised coordination complexes, e.g. organometallic complexes immobilised by covalent linkages, i.e. pendant complexes with optional linking groups, e.g. on Wang or Merrifield resins
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
- C08G77/382—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon
- C08G77/388—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing nitrogen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
- C08G77/382—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon
- C08G77/392—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
- C08G77/04—Polysiloxanes
- C08G77/38—Polysiloxanes modified by chemical after-treatment
- C08G77/382—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon
- C08G77/395—Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing phosphorus
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
- C08L83/04—Polysiloxanes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
- B01J2231/321—Hydroformylation, metalformylation, carbonylation or hydroaminomethylation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
- B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0202—Polynuclearity
- B01J2531/0205—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/824—Palladium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/847—Nickel
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
-
- Y02P20/588—
Definitions
- the invention relates to a process for the removal and return of a catalyst to a liquid phase medium and to a novel compound having pendant functional groups bound to a support, for example a new organopolysiloxane, and its use in selectively binding and releasing a species, for example a catalyst.
- the invention also relates to a process for reusing a catalyst for successive reactions and to a process for producing a product by a catalysed reaction in which the catalyst, which may have associated ancillary ligands, is selectively bound so as to remove it from a reaction environment.
- the invention may also involve a purification step where excess reagent may in addition to the catalyst be removed by the novel compound.
- the catalyst may subsequently be released back into the reaction environment for further use with or without excess reagent.
- the invention particularly relates to a process for the formation of a new covalent bond between a carbon atom and another atom selected from carbon, nitrogen, oxygen or other heteroatom through a homogeneously catalysed process in which the catalyst may be selectively removed and returned to the reaction. Such reactions are sometimes referred to as cross-coupling reactions.
- the invention also relates to a process for the production of the organopolysiloxane.
- Functionalised materials are employed in many different applications including as catalysts in solution phase synthesis and solid phase synthesis, solid phase extraction, as catalyst supports, in product purification and in the immobilisation of bio-molecules.
- functionalised materials employed in such applications require excellent physical and chemical stability over a wide range of operating conditions, broad solvent applicability, fast kinetics and functional groups with high intrinsic activity and selectivity for the desired application.
- preparation of such functionalised materials is desirably relatively simple and from readily available reagents in order for the synthesis to be economic and suitable for commercial scale production.
- Functionalised materials are also known for use in removing a component for example a catalyst, from a reaction medium.
- the removed, bound component may then be subjected to a further process for example recovery or recycling of the component for further use.
- Known treatments to recover the desired material include separation techniques, chemical regeneration and incineration. These treatments may be complex, expensive, inefficient or ineffective due to recycling in some cases being especially difficult.
- recovery and reuse of catalysts especially homogeneous catalysts from a reaction medium is particularly important to ensure residual levels of the catalyst in the reaction medium are kept to acceptably low levels so as not to be carried through in the synthesised product.
- Recovery and reuse of the catalyst provides advantage in managing operating costs, particularly as the active catalyst can contain both expensive metal and ligand components, and process efficiency and in reducing waste products.
- agrochemical and fine chemical manufacturing regulatory or safety issues may arise requiring levels of metals from catalysts to be below certain levels.
- phase separation methods separation methods in which functionalised ligands are employed to provide separation in homogeneous reaction media, for example sulfonated, quaternary ammonium salts where aqueous solubility is required and fluorous tags for fluorous liquid/liquid extraction.
- Another separation method involves the solid support of ligands onto magnetic nanoparticles.
- Membrane separation technology has also been employed.
- Catalysts containing metals find widescale application in the chemical and pharmaceutical sectors and are employed in a wide range of reactions including for example alpha arylation, amidation, amination, esterification, etherification, cyanation, and carbonylation and examples of metals used in catalysis include transition metals, for example platinum, palladium, rhodium, ruthenium, iridium, nickel, copper and iron.
- Homogeneous catalysis in organic synthesis provides benefits such as high activity, rapid kinetics however catalyst recovery and reuse may be problematic or in certain circumstances not possible. For potential reuse purposes, it is especially important that any work-up processes ensure the catalyst is retained in its active form. Heterogeneous catalysis provides rapid purification and workup and the catalyst may be recycled albeit with certain limitations, including reduced activity and slower kinetics, as mentioned above.
- the present invention aims to solve the problem of how to provide high catalytic activity and rapid kinetics in combination with efficient work-up and purification of the reaction product alongside efficient catalyst use and reuse.
- a catalyst may be selectively removed from a reaction medium for a period of time and then returned to the same or a different reaction medium affording the benefits of employing homogeneous catalysis in a reaction for example an organic synthesis, whilst gaining the benefits of a heterogeneous catalyst system, for example easier purification, whilst regenerating or recovering the catalyst.
- the invention provides a process for the selective removal of a component from a liquid phase medium and subsequently returning the component to a liquid phase medium comprising contacting a compound of formula I below with the liquid phase medium to bind the component to the compound I thereby forming a bound component, separating the bound component and the medium, subsequently returning the bound component to the medium and treating the bound component so as to release the component from compound I wherein the compound I is of formula:
- the support comprises a plurality of groups [L]-[G] at such a level as to provide a loading of 0.1 to 5, preferably 0.5 to 2 mmol of group [L]-[G] per gram of support.
- the term “leaving group” refers to a group which is capable of being substituted under certain conditions and includes Cl, Br, I, OH and pseudohalides.
- the term “pseudohalide” is well known in the chemical field and is employed herein in its conventional sense to mean a substituent that exhibits significant similarity to the halogens as regards their properties as leaving substituents and includes sulfonates including triflate, a diazo group, a nitrile, an ester and an alkoxy group.
- the leaving group LG may be located at any location on the group [G] provided it is sufficiently labile to act as a leaving group in the particular use. Preferably, the leaving group LG is located at a para position relative to the bond between groups [G] and [L].
- the heteroaromatic group is selected from:
- heterocyclic groups examples include:
- J and K are independently selected from, when divalent, O, NR, S and CH 2 or, when trivalent, ⁇ N—, ⁇ CH— and wherein HET signifies a heteroatom-containing species being present within the ring encircling HET.
- the G group is suitably linked to the L group via a carbon atom in the G group.
- the group Q may be located at any position in the heteraromatic group.
- the invention provides a process for selectively removing and reintroducing a catalyst to a reaction medium containing the catalyst comprising removing the catalyst from the reaction medium by contacting a compound of formula I with the reaction medium so as to bind the catalyst to the compound of formula I, treating the bound catalyst such that the catalyst is released in its active first form to the same or a different reaction medium.
- the support SUP is selected from a silica and alumina.
- a silica support is especially preferred.
- a silica or alumina support will have some unreacted hydroxyl groups and these may be end-capped in part or whole, preferably with an alkyl group, more preferably a C 1-6 alkyl group, for example propyl.
- the support SUP suitably comprises repeat units linked together to form a cross-linked matrix, for example a silica or alumina matrix and at least some of the silicon atoms or aluminium atoms have the groups [L]-[G] bound to them.
- the support SUP comprises a polymer
- the polymer is suitably selected from the group consisting of polystyrene, polyethylene glycol, poly(vinylpyrrolidine), poly(ethylene oxide), poly(vinyl chloride), polyethylenimine, polyacrylonitrile, poly(ethyleniminodiacetic acid), polyphazene, polysiloxanes, polyacrylamide, or a dendrimeric polymer, including block or copolymers thereof.
- the functional groups may be attached to the polymer chain by copolymerization with one or more monomers.
- the functionalised polymer may be prepared by functionalising the already formed polymer, for example as shown in Bergbreiter, Using Soluble Polymers to Recover Catalysts and Ligands, Chem. Rev. 102(10), 3345-3384 (2002), which is incorporated by reference.
- the functionalised polymer may be cross-linked or uncrosslinked.
- the polymer is cross-linked and has a crosslinker ratio ranging from 8 to 12 in moles of monomer to moles of crosslinking monomer.
- Exemplary classes of polymer backbones are disclosed in Bergbreiter, Using Soluble Polymers to Recover Catalysts and Ligands, Chem. Rev. 102(10) 3345-3384 (2002), which is incorporated by reference.
- the support SUP comprises silica and group G is an optionally substituted halo-aryl, heteroaryl or alkyl group.
- group G is an optionally substituted halo-aryl, heteroaryl or alkyl group.
- a silicon or aluminium atom does not have the group -[L]-[G]
- they suitably have all valencies satisfied by silicate or aluminate oxygen atoms.
- the silicate oxygen atoms or aluminate oxygen atoms are suitably saturated by:
- the component may be removed from a first liquid phase medium and returned to a second liquid phase medium but suitably the first and second liquid phase media are the same.
- the liquid phase medium is a reaction medium and the component participates in a chemical reaction in the medium.
- the component comprises a catalyst comprising a metal, for example, platinum, palladium, rhodium, ruthenium, iridium, nickel, copper and iron.
- the bound component may be separated from the first liquid phase medium by any suitable method, for example physical separation.
- the bound component may be released from the compound I by treating the bound component chemically, for example by contact with a compound, or physically, preferably by changing a reaction condition for example temperature, pressure or pH, so as to cause a shift in an equilibrium whereby the bound component is released from the compound I into the second liquid phase medium.
- the invention provides a homogeneously catalysed process for the formation of a covalent bond between a carbon atom and a second carbon atom or a heteroatom, for example nitrogen and oxygen in a reaction medium comprising a catalyst wherein the catalyst is selectively removed and returned to the reaction medium, the process comprising contacting a catalyst CAT with a compound of formula II R′′-LG to produce an organometallic species of formula III R′′-CAT-LG, treating -III with a compound IV R′′′′[MET] e [X′′] f to replace the leaving group LG with a group R′′′′ to form compound V R′′-R′′′′ and release the catalyst CAT into the reaction medium wherein R′′ and R′′′′ are independently selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, acyl, sulfonyl - or heterocyclic moiety, LG is a leaving group as hereinbefore defined, [MET] is selected from a
- the catalyst CAT may be any metallic element or compound containing metal.
- the catalyst comprises a metal species comprising a metal selected from Pd, Ni, Fe, Cu, Pt, Rh, Ru and Ir.
- R′′ and R′′′′ are independently selected from aryl, heteroaryl, alkyl and a heterocyclic moiety.
- R′′′′[MET] e [X′′] f is selected from R′′′′LiX′′, a Grignard reagent of formula R′′′′MgX′′ where X′′ is Cl or Br, R′′′′B(X′′) 2 , and R′′′′ZnCl.
- the invention enables a catalyst employed in a homogeneous reaction to be bound and removed from the reaction medium to enable recycling and extend its operating life and to provide flexibility of usage of the catalyst for different batches of the same reaction or for different reactions without needing to treat or regenerate the catalyst “off-line”.
- the homogeneous reaction may be continuous and the invention may remove the catalyst for treatment, for example to a zone in which the catalyst is separate from the reaction process, while the reaction process continues.
- the invention provides a novel compound of formula I.
- the compound I is preferably a novel organopolysiloxane containing a silica support and an aryl, heteroaryl, heterocyclic or alkyl moiety connected via a linking group.
- the invention provides a compound of formula (VI):
- heterocyclic groups examples include:
- J and K are independently selected from, when divalent, O, NR, S and CH 2 or, when trivalent, ⁇ N—, ⁇ CH— and wherein HET signifies a heteroatom-containing species being present within the ring encircling HET; wherein LG is a leaving group and is preferably selected from Cl, Br, I and a pseudohalide, a sulfonate, including triflate, a nitrile, a diazo group, an ester and an alkoxy group and substituent Q is selected from H, NR 2 , N + R 3 , —N(R)CO 2 H, —N ⁇ CR 2 , OR, —O + (R)SiR 3 , CO 2 R, CO 2 ⁇ , —CONR 2 —NRC(O)R F, Cl, NO 2 , CN and a ring formed between group Q and a part of group L, for example O—C(O)— where the ether oxygen is bound to G and the carbonyl group is
- the organopolysiloxane of the invention enables a component, for example a catalyst to be captured thereby removing it from a reaction medium and, upon contact with a further species or change in reaction conditions, allows the catalyst to be released back to the reaction medium.
- the catalyst may be bound to the organopolysiloxane and be released whilst being released to the reaction medium to act as a catalyst in a second reaction.
- the second reaction may involve the same substrates or different substrates.
- the compound of formula (VI) is a functionalised silica and advantageously does not swell to any appreciable degree in the reaction medium and therefore allows the compound VI to be used under continuous processing conditions by employment in a cartridge for contact with the reaction medium.
- the compound of formula VI is also chemically and physically stable and may be produced to a high level of purity enabling the compound VI to be employed in processes for the production of pharmaceuticals, agrochemicals or the like where high levels of quality control may be necessary.
- Polystyrene based materials may be limited to use in certain solvents and not used at temperatures above about 80° C.
- Organopolysiloxane compounds of Formula VI may be used in a wide range of solvents and are not limited in their application to reaction temperatures below 80° C.
- the porosity of the compound of formula VI may be varied from micro to macro porous and the loading of the functional groups as well as the other substituents in the fragment VI may be varied as needed.
- Compounds of Formula VI have the added advantage of their respective functional groups being firmly attached to a very stable and inert medium.
- linker group L is a divalent group linking G to (O 3/2 )Si— and is selected from:
- d is from 0 to 2, preferably 0, h is independently 0 to 4, preferably 2 or 3, m is independently 0 or 1, n is 0 to 4 and R is independently H, C 1-6 or phenyl, preferably H, methyl or ethyl;
- the linking group L which links the O 3/2 Si silica group to group G has a chain of at least three atoms between the silica group and group G.
- the linking group L has a chain length of not more than 15 atoms preferably 2 to 13 for example not more than 12 atoms between the silica group and group G.
- the linker group L comprises at least three parts, a —CH 2 CH 2 -bonded to the silica group, a link atom and optionally a connecting moiety.
- the link atom is located at the third atom along the linker group from the silica group and is selected from carbon, oxygen, sulphur, phosphorus and nitrogen. Sulphur and carbon are especially preferred as link atoms.
- Groups L may be respectively referred to as carbon-linked, oxygen-linked, sulphur-linked, phosphorus-linked or nitrogen-linked depending on the link atom.
- the linker group L is —[CH 2 CH 2 S(O) 0-2 ] 0-1 [CH 2 ] 0-3 [A′′] 0-1 - where A′′ is selected from:
- Examples of preferred carbon-linked groups L include —(CH 2 ) 3 —, —CH 2 CH 2 CHC((O)OCH 3 )—, CH 2 CH 2 CH(CN)—, —CH 2 CH 2 CH(CN)CONH(CH 2 ) 1-4 —, —(CH 2 ) 2-3 NHCO—, —(CH 2 ) 2-3 CONH—, (CH 2 ) 3 O(CH 2 ) 2 CHOHCH 2 NHCH 2 —, —(CH 2 ) 3 O(CH 2 ) 2 CHOHCH 2 S—, and —(CH 2 ) 3 NHCH 2 —.
- Examples of preferred sulphur-linked groups include —CH 2 CH 2 S—CH 2 CH 2 S(CH 2 ) 1-4 SCH 2 —, —CH 2 CH 2 S(CH 2 ) 1-4 NHCO—, —CH 2 CH 2 SCH 2 CONH(CH 2 ) 0-2 , —CH 2 CH 2 S(CH 2 ) 2 NH(CH 2 ) 0-2 —, —CH 2 CH 2 S(CH)(CH 2 CO)(CO)NCH 2 — and —(CH 2 ) 2 P( ⁇ O)(OR)O—.
- group G is preferably ortho, meta or para bromophenyl.
- the leaving group LG is suitably selected from a halide and a pseudohalide.
- the leaving group may be selected according to the particular reaction and catalyst with which the compound I is to be employed
- the catalyst to be bound comprises Pd
- LG is Br
- the catalyst comprises Cu
- LG is I
- the catalyst comprises Fe
- LG is Cl
- the catalyst comprises Ni
- LG is suitably ester, nitrile or alkoxy, for example methoxy.
- the aryl group G has a bromine substituent at the meta or para position of the benzene ring relative to the linker group L where group G is aryl.
- substituent Q of group G is selected from H, NR 2 , N + R 3 , —N(R)CO 2 H, —N ⁇ CR 2 , OR, —O + (R)SiR 3 , CO 2 R, CO 2 ⁇ , CONR 2 NRC(O)R, F, Cl, NO 2 , CN and a ring formed between group Q and a part of group L, for example O—C(O)— where the ether oxygen is bound to G and the carbonyl group is a part of group L.
- substituent Q is located at the ortho or meta position relative to linker group L where group G is aryl.
- the aryl group G with substituent Q may be in equilibrium between two forms and, optionally may be derivatised.
- movement of the equilibrium may be affected by altering reaction conditions, for example pH or by adding a component so providing a means of controlling or tuning the position at which the equilibrium lies and controlling the level of binding or release of the catalyst.
- Examples of preferred groups G with substituents Q which may be in equilibrium between two forms.
- Q is OH, it is preferably located at the ortho position and linker group L comprises a group which is capable of reversibly forming a ring with the OH substituent, preferably L comprises a pendant acid or ester group CO 2 R where the OH substituent and acid or ester group may form a ring.
- Q is NR 2 , preferably NHR or NH 2
- this group may reversibly form an ammonium ion N + H 3 or N + R 3 by altering the pH, or to N(R)CO 2 H in the presence of free CO 2 .
- Substituent Q may be —OR, preferably —OCH 3 and may be reversibly converted to —O + (R)—SiR 3 in the presence of a trialkyl silane.
- substituent Q is CO 2 H
- changing the pH may reversibly convert this group to a carbon/late anion.
- R is NH 2
- acetone or other carbonyl functionality may be added to derivatise the amine to the corresponding imines and for example in the case of acetone the reaction may be reversed by washing with water.
- group Q may exist in more than one form so enabling control of the position of the equilibrium.
- the invention provides for use of a compound of formula I, preferably a compound of formula VI to selectively remove a component from a reaction medium so the component may be treated and subsequently return the component to the reaction medium.
- the component to be removed from a reaction medium is one or more of a catalyst and unreacted feedstock. Unreacted feedstock typically is not subsequently returned to the reaction medium.
- the component to be removed comprises a metal with or without ancilliary ligands, more preferably a metal of Group 8, 9, 10 or 11 of the Periodic Table. Examples of preferred metals include palladium, platinum, rhodium, ruthenium, iridium, nickel, copper and iron, optionally comprising ancilliary ligands.
- the invention comprises an organometallic species of a catalyst CAT and a compound of formula I, preferably a compound of formula VI wherein CAT comprises a metal with or without ancilliary ligands.
- the catalyst CAT preferably comprises palladium, platinum, rhodium, iridium, ruthenium, copper, nickel or iron, optionally comprising ancilliary ligands.
- the catalyst CAT is preferably bound to the compound I at group G which has a substituent Q and a leaving group LG as hereinbefore defined.
- the catalyst CAT is interposed between the aryl, heteroaryl or alkyl group of group G and leaving group LG as shown in formula VII below:
- the compound for treating the species of formula VII is suitably of formula R′′′′[MET] e [X′′] f , (compound IV), as hereinbefore defined or a salt thereof, preferably an alkali metal salt M′′X′′, for example R′′′′B(OH) 3 ⁇ K + ) and after contacting with the compound of formula VII, the catalyst CAT is released into a reaction medium.
- a salt thereof preferably an alkali metal salt M′′X′′, for example R′′′′B(OH) 3 ⁇ K +
- the catalyst CAT is suitably employed in a homogeneously catalysed process for the formation of a new carbon carbon, carbon nitrogen, carbon oxygen or other carbon heteroatom bond through a homogeneously catalysed process in which the catalyst may be selectively removed and returned to the reaction, the process involving the addition of a catalyst to a compound of formula R′′-LG, wherein LG is a leaving group as hereinbefore defined, to produce an organometallic species of formula VIII R′′-CAT-LG, treating the compound VIII whereby LG is replaced by a group selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, or heterocyclic moiety to provide a species of formula IX R′′-CAT-R′′′′ wherein R′′ and R′′′′ are independently selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, or heterocyclic moiety.
- the compound for treating the species of formula VIII is suitably of formula R′′′′[MET] e [X′′] f as hereinbefore defined or a salt thereof and after contacting with the compound of formula VIII, the compound of formula IX and [MET] e [X′′] f+1 is produced.
- the compound of formula IX may then be treated to release catalyst CAT into a reaction medium and to form compound R′′-R′′′′.
- the catalyst may then suitably be recovered from the reaction medium by binding with a compound of formula I or VI, thereby allowing the reaction medium to be treated for example to remove by-products, unreacted reactants and the like or to allow new reactants to be introduced or to alter reaction conditions in the absence of the catalyst.
- the captured catalyst may then be returned to the reaction medium as required.
- LG is a halide or a pseudo halide as hereinbefore defined for example triflate, or under catalysis conditions with certain metals, an alkoxide, an ester and a nitrile.
- organopolysiloxanes of the invention are especially suited to recovery of metal catalysts employed in a wide range of reactions in which an aryl, vinyl, heterocyclic or alkyl boronic acid is reacted with an aryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, acyl, sulfonyl or heterocyclic halide or pseudo halide catalyzed by a metal catalyst.
- the invention provides a process for producing a reaction product by homogeneous catalysis comprising reacting a feedstock in the presence of a homogeneous catalyst in a reaction medium to produce directly or indirectly a reaction product, contacting the catalyst with a compound of formula I, preferably formula VI to remove the catalyst from the reaction medium to produce an organometallic species comprising the catalyst bound to the compound of formula I, preferably VI, treating the catalyst, returning the catalyst to the reaction medium and reacting a second feedstock in the presence of the returned homogeneous catalyst to produce a second reaction product or a second batch of the same reaction product.
- the first and second feedstocks may be the same or different.
- the first and any subsequent feedstocks are advantageously the same, for regulatory reasons.
- different feedstocks may be employed. Removal of the catalyst allows the catalyst life to be extended and the compound of formula I beneficially purifies the reaction product by removing excess feedstock as well as the catalyst to be regenerated from the reaction medium.
- the catalyst upon removal from the reaction medium is temporarily in heterogeneous form and is suitably released into the reaction medium by contact of the bound catalyst with the second feedstock.
- the process of removing the catalyst from a reaction medium to form an organometallic species treating the species and reintroducing the catalyst into the same or a different reaction medium may be repeated as desired.
- the process allows removal of excess reagent thereby improving product isolation.
- the invention provides a process for producing a reaction product comprising a coupled biaryl, aryl-heteroaryl, aryl-alkyl, heteroaryl-alkyl, biheteroaryl, bialkyl reaction product by homogeneous catalysis comprising reacting a feedstock comprising a compound of formula R′′′′[MET] e [X′′] f or R′′′′[MET] e [X′′] f ⁇ M′′ + with a compound of formula R′′Br in the presence of a homogeneous catalyst comprising a metal in a reaction medium to produce a coupled biaryl product of formula R′′-R′′′′, contacting the catalyst with a compound of formula I, preferably a compound of formula VI
- the catalyst may comprise any metal suitable for the reaction being carried out.
- suitable catalysts for treatment according to methods of the invention include Pt, Pd, Ni, Fe, Cu, Ir, Ru, Rh.
- the invention enables a metal catalyst to be removed from and reintroduced to a reaction medium together with any associated ancilliary ligands that may be present.
- the catalyst may comprise Pd, Ni and Fe, especially for Suzuki reactions, Pd, Cu, Ni and Fe for formation of C—N and C—O bonds, Pd, Ni, Fe, Cu, Ir, Ru, Rh for formation of a C—C bond.
- suitable palladium catalysts include palladium combined with a phosphine including monodentate and bidentatephosphines, a phosphite, a phosphoramidite, a carbene, ligands containing nitrogen and ligands containing oxygen, and any combination of two or more of these groups.
- Examples of specific palladium catalysts include palladium acetate, bis(triphenylphosphine) palladium chloride or acetate and tetrakis(triphenylphosphine)palladium(0), include tris-dibenzylideneacetone di-palladium(0) plus other palladium ligand salts plus other metals.
- the present invention enables catalysts to be removed from a wide-range of catalyzed reactions including alpha arylation (metal enolate), amidation, amination, etherification, esterification, cyanation (cyanide ion), and carbonylation reactions.
- Examples of particular reactions in which the present invention may be employed for catalyst removal and reintroduction include Miyaura borylation (pinacol borylation), Buchwald Hartwig amination (primary or secondary amine), Ullman etherification, Ullmann amination (Goldberg reaction), carbonylation for hydroformylation, ester, acid, amide and diketone formation, Chan Lam amination, Mizoroki Heck reaction (alkene), Sonogashira reaction (alkyne), Hiyama reaction (ArSi), Kumada Corriu reaction, Negishi reaction, reductive Heck Reaction, Tsuji Trost reaction (enolate), Stille reaction and Suzuki Miyaura reaction.
- the process for producing a reaction product may be carried out in a batch process although a continuous process may be employed.
- the catalyst and feedstocks are fed to a reaction zone.
- the compound of the invention is suitably located in a separate bed, for example a conventional cartridge arrangement, in a recycle loop around the reaction zone.
- the reaction is carried out in the reaction zone, the reaction mixture is then passed through the separate bed and contacted with the compound of the invention.
- the catalyst and, as desired unreacted feedstocks are bound in the bed and the reaction mixture depleted in these components is fed elsewhere.
- a new feedstock, comprising the same or different components to those previously employed or coupling partner is then passed through the bed and releases the catalyst from the bed and is carried back to the reaction zone where the second or subsequent reaction is carried out.
- silicas and aluminas suitable for functionalization to produce a compound of formula I or VI include any silica or alumina having surface Si(OH) or Al(OH) moieties respectively.
- the silica or alumina may be produced by treating a commercially available silica or alumina with alkenyl trialkoxysilane, for example vinyl trimethoxy silane available from Sigma Aldrich (cat no. 235768).
- Sulphur-linked compounds may be produced by treating with a thiol under radical generating conditions to afford a sulphur-linked compound of formula I or VI.
- a functionalised trialkoxysilane may be produced by reacting with a species to produce the desired functional group and which is then coated on or reacted with an existing support of silica or alumina.
- compound I or VI comprises a polymer, for example polystyrene support
- copolymerisation of a commercially available functionalised monomer for example a functionalised styrene with a monomer, for example styrene, with or without copolymer additives affords the functionalised polymer support.
- functionalization of a pre-formed polymer may also be employed using conventional methods.
- Cysteamine hydrochloride (193.10 g, 1.7 mol) was stirred and heated to 120° C. When the material had become molten, vinyl trimethoxysilane (229.95 g, 1.55 mol) and tert-butyl peroxide (2.0 mL, 10.89 mmol) was added over 30 min. The heterogeneous mixture was heated at 120-130° C. for a further hour, before a second addition of tert-butyl peroxide (2.0 mL, 10.9 mmol). The reaction mixture was stirred for 2 hours at this temperature whereupon the solution had become homogeneous. The solution was then cooled to room temperature to provide a crude product.
- 3-aminopropyl functionalised silica (from above) (5.00 g, 1.25 mmol/g functional group loading) is added and stirring continued for 1 h whereupon the reaction mixture is filtered and the silica washed with methanol, water, 1 M aqueous Na 2 CO 3 , water and methanol and dried in a vacuum oven. The structure was verified by NMR techniques.
- trimethoxyvinylsilane (1.48 g, 10.0 mmol), 4-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 4-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- 3-Bromobenzylamine hydrochloride (8.90 g, 40 mmol), aqueous sodium carbonate solution (50 mL, 1 M) and toluene (50 mL) were stirred and heated to approx. 100° C. for 1 h (or until all solid has dissolved) whereupon the mixture was allowed to cool and the phases separated.
- the organic phase was then added to a mixture of succinic acid ethyl sulphide silica (29 g, 1.4 mmol/g loading), methane sulfonic acid (0.19 g, 2 mmol) and toluene (50 mL).
- the resultant mixture was heated at reflux under Dean-Stark conditions for 4 h before being allowed to cool.
- the solid was filtered and washed with toluene and methanol and dried in a vacuum oven. The structure was verified by NMR techniques.
- trimethoxyvinylsilane (1.48 g, 10.0 mmol), 2-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 2-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- trimethoxyvinylsilane (1.48 g, 10.0 mmol), 3-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 3-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- trimethoxyvinylsilane (1.48 g, 10.0 mmol), 4-chlorothiophenol (2.17 g, 15.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 4-chlorothiophenol (1.00 g, 7.0 mmol) being added after 3 h.
- Example 15 Production of 4-Bromophenyl sulfide ethyl; propyl functionalised Silica
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Materials Engineering (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Silicon Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
Description
- This application is a continuation of U.S. application Ser. No. 14/647,919, filed Jun. 12, 2015, which is a 35 U.S.C. § 371 filing of International Application No. PCT/EP2013/074974, filed Nov. 28, 2013, which claims priority to United Kingdom patent application number 1221402.9, filed Nov. 28, 2012. The entire contents of these applications are incorporated by reference herein, in their entirety.
- The invention relates to a process for the removal and return of a catalyst to a liquid phase medium and to a novel compound having pendant functional groups bound to a support, for example a new organopolysiloxane, and its use in selectively binding and releasing a species, for example a catalyst. The invention also relates to a process for reusing a catalyst for successive reactions and to a process for producing a product by a catalysed reaction in which the catalyst, which may have associated ancillary ligands, is selectively bound so as to remove it from a reaction environment. The invention may also involve a purification step where excess reagent may in addition to the catalyst be removed by the novel compound. The catalyst may subsequently be released back into the reaction environment for further use with or without excess reagent. The invention particularly relates to a process for the formation of a new covalent bond between a carbon atom and another atom selected from carbon, nitrogen, oxygen or other heteroatom through a homogeneously catalysed process in which the catalyst may be selectively removed and returned to the reaction. Such reactions are sometimes referred to as cross-coupling reactions. The invention also relates to a process for the production of the organopolysiloxane.
- Functionalised materials are employed in many different applications including as catalysts in solution phase synthesis and solid phase synthesis, solid phase extraction, as catalyst supports, in product purification and in the immobilisation of bio-molecules. Typically, functionalised materials employed in such applications require excellent physical and chemical stability over a wide range of operating conditions, broad solvent applicability, fast kinetics and functional groups with high intrinsic activity and selectivity for the desired application. In addition, the preparation of such functionalised materials is desirably relatively simple and from readily available reagents in order for the synthesis to be economic and suitable for commercial scale production.
- Functionalised materials are also known for use in removing a component for example a catalyst, from a reaction medium. The removed, bound component may then be subjected to a further process for example recovery or recycling of the component for further use. Known treatments to recover the desired material include separation techniques, chemical regeneration and incineration. These treatments may be complex, expensive, inefficient or ineffective due to recycling in some cases being especially difficult.
- In the chemical and pharmaceutical industries, recovery and reuse of catalysts especially homogeneous catalysts from a reaction medium is particularly important to ensure residual levels of the catalyst in the reaction medium are kept to acceptably low levels so as not to be carried through in the synthesised product. Recovery and reuse of the catalyst provides advantage in managing operating costs, particularly as the active catalyst can contain both expensive metal and ligand components, and process efficiency and in reducing waste products. In pharmaceutical, agrochemical and fine chemical manufacturing regulatory or safety issues may arise requiring levels of metals from catalysts to be below certain levels. Various methods are known for recovery of catalysts and catalyst components including phase separation methods, separation methods in which functionalised ligands are employed to provide separation in homogeneous reaction media, for example sulfonated, quaternary ammonium salts where aqueous solubility is required and fluorous tags for fluorous liquid/liquid extraction. Another separation method involves the solid support of ligands onto magnetic nanoparticles. Membrane separation technology has also been employed. These recovery methods tend to be relatively complex and costly and the catalyst is removed from the reaction process for treatment “off-line” or separately from the reaction process, necessitating additional charges of catalyst to allow the reaction process to continue to be operated while the spent catalyst is recovered and treated for reuse.
- Efficient recovery of metals is important due to the intrinsic value of the metal, limited availability of certain metals, improving product purity and due to environmental considerations for example reducing the requirement for waste treatment or management. There remains a need for materials which are able to recover metals or other species containing metals for example catalysts. Catalysts containing metals find widescale application in the chemical and pharmaceutical sectors and are employed in a wide range of reactions including for example alpha arylation, amidation, amination, esterification, etherification, cyanation, and carbonylation and examples of metals used in catalysis include transition metals, for example platinum, palladium, rhodium, ruthenium, iridium, nickel, copper and iron.
- Homogeneous catalysis in organic synthesis provides benefits such as high activity, rapid kinetics however catalyst recovery and reuse may be problematic or in certain circumstances not possible. For potential reuse purposes, it is especially important that any work-up processes ensure the catalyst is retained in its active form. Heterogeneous catalysis provides rapid purification and workup and the catalyst may be recycled albeit with certain limitations, including reduced activity and slower kinetics, as mentioned above.
- The present invention aims to solve the problem of how to provide high catalytic activity and rapid kinetics in combination with efficient work-up and purification of the reaction product alongside efficient catalyst use and reuse. We have now found that a catalyst may be selectively removed from a reaction medium for a period of time and then returned to the same or a different reaction medium affording the benefits of employing homogeneous catalysis in a reaction for example an organic synthesis, whilst gaining the benefits of a heterogeneous catalyst system, for example easier purification, whilst regenerating or recovering the catalyst.
- In a first aspect the invention provides a process for the selective removal of a component from a liquid phase medium and subsequently returning the component to a liquid phase medium comprising contacting a compound of formula I below with the liquid phase medium to bind the component to the compound I thereby forming a bound component, separating the bound component and the medium, subsequently returning the bound component to the medium and treating the bound component so as to release the component from compound I wherein the compound I is of formula:
-
[SUP][[L]-[G]]n (I) - wherein:
-
- L is a group linking G to SUP— and is selected from:
i) —(CH2)h[S(O)d]m(CHD)nZm((CH2)nY(CH2)n)m where D is selected from H, CN, OH, —C(O)OR, —C(O)NR2—C(O)OG, —CONRG and Y is selected from O, NR, S(O)d, CO, CO2, —NRCOZm—, —ZmCONR—, —C═N—, a heterocyclic ring where Z is independently O, S, NR; and
ii) —(CH2)h P(═O)(OR)O—(CH2)h
and wherein d is independently 0 to 2, preferably 0, h is from 0 to 15, more preferably from 0 to 12, especially 0 to 4, optimally 2 or 3, m is independently 0 or 1 and n is independently 0 to 4 and R is independently selected from H or a C1-12 alkyl group, preferably C1-6alkyl group for example methyl or ethyl, or a phenyl group; or L is not present and G is linked directly to SUP; - G is selected from an alkyl group, an aryl group, a heterocyclic group and a heteroaryl group, preferably an aromatic group or a heteraromatic group having one or two aromatic rings;
wherein the group G has
i) a leaving group LG and is preferably selected from Cl, Br, I, a pseudohalide; and
ii) substituent Q selected from H, NR2, N+R3, —N(R)CO2H, —N═CR2, OR, —O+(R)SiR3, CO2R, CO2 −, —CONR2—NRC(O)R, F, Cl, NO2, CN and a ring formed between group Q and a part of group L, for example O—C(O)— where the ether oxygen is bound to G and the carbonyl group is a part of group L;
SUP is a support, preferably a chemically inert support, having a plurality n of groups [L]-[G] bound to the support.
- L is a group linking G to SUP— and is selected from:
- Preferably, the support comprises a plurality of groups [L]-[G] at such a level as to provide a loading of 0.1 to 5, preferably 0.5 to 2 mmol of group [L]-[G] per gram of support.
- The term “leaving group” refers to a group which is capable of being substituted under certain conditions and includes Cl, Br, I, OH and pseudohalides. The term “pseudohalide” is well known in the chemical field and is employed herein in its conventional sense to mean a substituent that exhibits significant similarity to the halogens as regards their properties as leaving substituents and includes sulfonates including triflate, a diazo group, a nitrile, an ester and an alkoxy group. The leaving group LG may be located at any location on the group [G] provided it is sufficiently labile to act as a leaving group in the particular use. Preferably, the leaving group LG is located at a para position relative to the bond between groups [G] and [L].
- Preferably, the heteroaromatic group is selected from:
- Examples of suitable heterocyclic groups include:
- wherein J and K are independently selected from, when divalent, O, NR, S and CH2 or, when trivalent, ═N—, ═CH— and wherein HET signifies a heteroatom-containing species being present within the ring encircling HET. In this case, the G group is suitably linked to the L group via a carbon atom in the G group. The group Q may be located at any position in the heteraromatic group.
- The invention provides a process for selectively removing and reintroducing a catalyst to a reaction medium containing the catalyst comprising removing the catalyst from the reaction medium by contacting a compound of formula I with the reaction medium so as to bind the catalyst to the compound of formula I, treating the bound catalyst such that the catalyst is released in its active first form to the same or a different reaction medium.
- Preferably the support SUP is selected from a silica and alumina. A silica support is especially preferred. A silica or alumina support will have some unreacted hydroxyl groups and these may be end-capped in part or whole, preferably with an alkyl group, more preferably a C1-6 alkyl group, for example propyl. The support SUP suitably comprises repeat units linked together to form a cross-linked matrix, for example a silica or alumina matrix and at least some of the silicon atoms or aluminium atoms have the groups [L]-[G] bound to them. Where the support SUP comprises a polymer, the polymer is suitably selected from the group consisting of polystyrene, polyethylene glycol, poly(vinylpyrrolidine), poly(ethylene oxide), poly(vinyl chloride), polyethylenimine, polyacrylonitrile, poly(ethyleniminodiacetic acid), polyphazene, polysiloxanes, polyacrylamide, or a dendrimeric polymer, including block or copolymers thereof. The functional groups may be attached to the polymer chain by copolymerization with one or more monomers. Alternatively, the functionalised polymer may be prepared by functionalising the already formed polymer, for example as shown in Bergbreiter, Using Soluble Polymers to Recover Catalysts and Ligands, Chem. Rev. 102(10), 3345-3384 (2002), which is incorporated by reference. The functionalised polymer may be cross-linked or uncrosslinked. In one aspect, the polymer is cross-linked and has a crosslinker ratio ranging from 8 to 12 in moles of monomer to moles of crosslinking monomer. Exemplary classes of polymer backbones are disclosed in Bergbreiter, Using Soluble Polymers to Recover Catalysts and Ligands, Chem. Rev. 102(10) 3345-3384 (2002), which is incorporated by reference.
- Preferably, the support SUP comprises silica and group G is an optionally substituted halo-aryl, heteroaryl or alkyl group. Where a silicon or aluminium atom does not have the group -[L]-[G], they suitably have all valencies satisfied by silicate or aluminate oxygen atoms. The silicate oxygen atoms or aluminate oxygen atoms are suitably saturated by:
- silicon or aluminium atoms of other repeat units;
hydrogen;
a linear or branched C1-12-alkyl group;
an end group of formula R8 3M1O1,2, a cross-linking bridge member or a polymer chains of formula R8 qM1(OR9)jOk/2 or Al(OR9)3-pOp/2 or R8Al(OR9)2-rOr/2 where M1 is Si or Ti;
R8 and R9 are independently selected from a linear or branched C1-40 alkyl group an aryl group and a C1-40-alkylaryl group; k is an integer from 1 to 3, q is an integer from 1 to 2 and j is an integer from 0 to 2 such that j+k+q=4, where; p is an integer from 1 to 3; and r is an integer from 1 to 2; and
other known oxo metal bridging systems where the metal is zirconium, boron, magnesium, iron, nickel or a lanthanide. - The component may be removed from a first liquid phase medium and returned to a second liquid phase medium but suitably the first and second liquid phase media are the same. More preferably the liquid phase medium is a reaction medium and the component participates in a chemical reaction in the medium. Preferably the component comprises a catalyst comprising a metal, for example, platinum, palladium, rhodium, ruthenium, iridium, nickel, copper and iron.
- The bound component may be separated from the first liquid phase medium by any suitable method, for example physical separation. The bound component may be released from the compound I by treating the bound component chemically, for example by contact with a compound, or physically, preferably by changing a reaction condition for example temperature, pressure or pH, so as to cause a shift in an equilibrium whereby the bound component is released from the compound I into the second liquid phase medium.
- In a second aspect, the invention provides a homogeneously catalysed process for the formation of a covalent bond between a carbon atom and a second carbon atom or a heteroatom, for example nitrogen and oxygen in a reaction medium comprising a catalyst wherein the catalyst is selectively removed and returned to the reaction medium, the process comprising contacting a catalyst CAT with a compound of formula II R″-LG to produce an organometallic species of formula III R″-CAT-LG, treating -III with a compound IV R″″[MET]e[X″]f to replace the leaving group LG with a group R″″ to form compound V R″-R″″ and release the catalyst CAT into the reaction medium wherein R″ and R″″ are independently selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, acyl, sulfonyl - or heterocyclic moiety, LG is a leaving group as hereinbefore defined, [MET] is selected from a metal capable of use in an organometallic species, preferably Mg or Zn, and boron, X″ is selected from halogen, preferably F, Cl or Br, and OH, e is 0 or 1 and f is an integer from 1 to 4, preferably 1 and 2, selected to satisfy the free valencies of species R″″[MET]e.
- The catalyst CAT may be any metallic element or compound containing metal. In a preferred embodiment, the catalyst comprises a metal species comprising a metal selected from Pd, Ni, Fe, Cu, Pt, Rh, Ru and Ir.
- Preferably R″ and R″″ are independently selected from aryl, heteroaryl, alkyl and a heterocyclic moiety.
- Preferably the compound IV R″″[MET]e[X″]f is selected from R″″LiX″, a Grignard reagent of formula R″″MgX″ where X″ is Cl or Br, R″″B(X″)2, and R″″ZnCl.
- Advantageously, the invention enables a catalyst employed in a homogeneous reaction to be bound and removed from the reaction medium to enable recycling and extend its operating life and to provide flexibility of usage of the catalyst for different batches of the same reaction or for different reactions without needing to treat or regenerate the catalyst “off-line”. The homogeneous reaction may be continuous and the invention may remove the catalyst for treatment, for example to a zone in which the catalyst is separate from the reaction process, while the reaction process continues.
- In a third aspect, the invention provides a novel compound of formula I.
- The compound I is preferably a novel organopolysiloxane containing a silica support and an aryl, heteroaryl, heterocyclic or alkyl moiety connected via a linking group.
- In a fourth aspect, the invention provides a compound of formula (VI):
-
[(O3/2)Si[L]G]a[SI(O4/2)]b[Si(O3/2)V]c - wherein:
-
- L is a group linking G to (O3/2)Si— and is selected from:
i) —(CH2)h[S(O)d]m(CHD)nZm((CH2)dY(CH2)n)m where D is selected from H, CN, OH, —C(O)OR, —C(O)NR2—C(O)OG, —CONRG and Y is selected from O, NR, S(O)d, CO, CO2, —NRCOZm—, —ZmCONR—, —C═N—, a heterocyclic ring, for example succinimide, where Z is independently O, S, NR; and
ii) —(CH2)h P(═O)(OR)O—(CH2)h
and wherein d is independently 0 to 2, preferably 0, h is from 0 to 15, more preferably from 0 to 12, optimally 0 to 4, especially 2 or 3, m is independently 0 or 1 and n is independently 0 to 4 and R is independently selected from H or a C1-12 alkyl group, preferably C1-6 alkyl group for example methyl or ethyl, or a phenyl group; - G is an alkyl group, preferably selected from C1-12 alkyl group and more preferably a C1-6 alkyl group, an aryl group, a heterocyclic group or a heteroaryl group, preferably an aromatic group or a heteroaromatic group having one or two aromatic rings, selected from:
- L is a group linking G to (O3/2)Si— and is selected from:
- Examples of suitable heterocyclic groups include:
- wherein J and K are independently selected from, when divalent, O, NR, S and CH2 or, when trivalent, ═N—, ═CH— and wherein HET signifies a heteroatom-containing species being present within the ring encircling HET;
wherein LG is a leaving group and is preferably selected from Cl, Br, I and a pseudohalide, a sulfonate, including triflate, a nitrile, a diazo group, an ester and an alkoxy group and substituent Q is selected from H, NR2, N+R3, —N(R)CO2H, —N═CR2, OR, —O+(R)SiR3, CO2R, CO2 −, —CONR2—NRC(O)R F, Cl, NO2, CN and a ring formed between group Q and a part of group L, for example O—C(O)— where the ether oxygen is bound to G and the carbonyl group is a part of group L;
V is an optionally substituted C1-12 alkyl, C2-12 alkenyl or C2-12 alkynyl group or an aryl group or C1-12 alkylaryl sulfide, sulfoxide, sulfone, amine or a polyalkyl amine or phosphine or other phosphorous containing group;
the free valences of the silicate oxygen atoms are saturated by one or more groups selected from:
silicon atoms of other groups of Formula VI;
hydrogen;
a linear or branched C1-12 alkyl group;
an end group of formula R8 3M1O1/2, a cross-linking bridge member or a polymer chains of formula R8 qM1(OR9)jOk/2 or Al(OR9)3-pOp/2 or R8Al(OR9)2-rOr/2 where M1 is Si or Ti;
R8 and R9 are independently selected from a linear or branched C1-40 alkyl group an aryl group and a C1-40 alkylaryl group; k is an integer from 1 to 3, q is an integer from 1 to 2 and j is an integer from 0 to 2 such that j+k+q=4; p is an integer from 1 to 3; and r is an integer from 1 to 2; and
other known oxo metal bridging systems where the metal is zirconium, boron, magnesium, iron, nickel or a lanthanide; and
a, b and c are integers, a is greater than 0 and a, b and c are such that when b is 0 the ratio of a:c is from 0.001 to 1000 and when b is 1 or more the ratio of a:b is from 0.001 to 1000. - Advantageously the organopolysiloxane of the invention enables a component, for example a catalyst to be captured thereby removing it from a reaction medium and, upon contact with a further species or change in reaction conditions, allows the catalyst to be released back to the reaction medium. The catalyst may be bound to the organopolysiloxane and be released whilst being released to the reaction medium to act as a catalyst in a second reaction. The second reaction may involve the same substrates or different substrates.
- The compound of formula (VI) is a functionalised silica and advantageously does not swell to any appreciable degree in the reaction medium and therefore allows the compound VI to be used under continuous processing conditions by employment in a cartridge for contact with the reaction medium. The compound of formula VI is also chemically and physically stable and may be produced to a high level of purity enabling the compound VI to be employed in processes for the production of pharmaceuticals, agrochemicals or the like where high levels of quality control may be necessary. Polystyrene based materials may be limited to use in certain solvents and not used at temperatures above about 80° C. Organopolysiloxane compounds of Formula VI may be used in a wide range of solvents and are not limited in their application to reaction temperatures below 80° C.
- Other advantages include fixed and rigid structures, insolubility in organic solvents, high resistance to ageing, relatively easy purification and high reusability. In addition the processes for the preparation of compounds of Formula VI are flexible, allowing a wide range of functionalised materials with different linking groups L or groups G with substituents Q and LG to be made from a small number of common intermediates.
- The porosity of the compound of formula VI may be varied from micro to macro porous and the loading of the functional groups as well as the other substituents in the fragment VI may be varied as needed. Compounds of Formula VI have the added advantage of their respective functional groups being firmly attached to a very stable and inert medium.
- Preferably linker group L is a divalent group linking G to (O3/2)Si— and is selected from:
-
- i) —(CH2)h(CHD)n(Y)m(CH2)h— where D is selected from H, CN, OH and C(O)OR, Y is selected from —N(R)—, —O—, —S(O)d, —CO2—, —CON(R)—, —N(R)CO—, C(R)═N— and a cyclic divalent moiety, preferably
- d is from 0 to 2, preferably 0, h is independently 0 to 4, preferably 2 or 3, m is independently 0 or 1, n is 0 to 4 and R is independently H, C1-6 or phenyl, preferably H, methyl or ethyl;
-
- ii) —(CH2)h S(O)d(CH2)n(Y)m(CH2)h where Y is selected from —CO2—, —CON(R)—, — and —N(R)CO—, h is independently 0 to 4, preferably 2 or 3, m is independently 0 or 1, n is independently 0 to 4 and d is from 0 to 2, preferably 0, and R is independently H, C1-6 or phenyl, preferably H, methyl or ethyl; and
- iii) —(CH2)h P(═O)(OR)O—(CH2)h where h is independently 0 to 4, preferably 2 or 3.
- In a preferred embodiment, the linking group L which links the O3/2Si silica group to group G has a chain of at least three atoms between the silica group and group G. Suitably, the linking group L has a chain length of not more than 15 atoms preferably 2 to 13 for example not more than 12 atoms between the silica group and group G. In an especially preferred embodiment, the linker group L comprises at least three parts, a —CH2CH2-bonded to the silica group, a link atom and optionally a connecting moiety. Preferably, the link atom is located at the third atom along the linker group from the silica group and is selected from carbon, oxygen, sulphur, phosphorus and nitrogen. Sulphur and carbon are especially preferred as link atoms. Groups L may be respectively referred to as carbon-linked, oxygen-linked, sulphur-linked, phosphorus-linked or nitrogen-linked depending on the link atom.
- Preferably the linker group L is —[CH2CH2S(O)0-2]0-1[CH2]0-3[A″]0-1- where A″ is selected from:
-
- —NH(CO)—,
- —CH(CH2CO)(CO)NCH2—
- —N(CO)(CO) where group G comprises an aromatic ring and the carbonyl carbon atoms are bound directly to adjacent carbon atoms in the aromatic ring,
- —N(CH3)—
- —O(CO)0-1—
- Examples of preferred carbon-linked groups L include —(CH2)3—, —CH2CH2CHC((O)OCH3)—, CH2CH2CH(CN)—, —CH2CH2CH(CN)CONH(CH2)1-4—, —(CH2)2-3NHCO—, —(CH2)2-3CONH—, (CH2)3O(CH2)2CHOHCH2NHCH2—, —(CH2)3O(CH2)2CHOHCH2S—, and —(CH2)3NHCH2—. Examples of preferred sulphur-linked groups include —CH2CH2S—CH2CH2S(CH2)1-4SCH2—, —CH2CH2S(CH2)1-4NHCO—, —CH2CH2SCH2CONH(CH2)0-2, —CH2CH2S(CH2)2NH(CH2)0-2—, —CH2CH2S(CH)(CH2CO)(CO)NCH2— and —(CH2)2P(═O)(OR)O—.
- In combination with the preferred linker groups, group G is preferably ortho, meta or para bromophenyl.
- The leaving group LG is suitably selected from a halide and a pseudohalide. The leaving group may be selected according to the particular reaction and catalyst with which the compound I is to be employed
- In preferred embodiments, where the catalyst to be bound comprises Pd, LG is Br, where the catalyst comprises Cu, LG is I and where the catalyst comprises Fe, LG is Cl. Where the catalyst comprises Ni, LG is suitably ester, nitrile or alkoxy, for example methoxy. In an especially preferred embodiment the aryl group G has a bromine substituent at the meta or para position of the benzene ring relative to the linker group L where group G is aryl.
- In a preferred embodiment, substituent Q of group G is selected from H, NR2, N+R3, —N(R)CO2H, —N═CR2, OR, —O+(R)SiR3, CO2R, CO2 −, CONR2 NRC(O)R, F, Cl, NO2, CN and a ring formed between group Q and a part of group L, for example O—C(O)— where the ether oxygen is bound to G and the carbonyl group is a part of group L. Suitably, substituent Q is located at the ortho or meta position relative to linker group L where group G is aryl.
- In another preferred embodiment, the aryl group G with substituent Q may be in equilibrium between two forms and, optionally may be derivatised. By selecting appropriate substituents Q, movement of the equilibrium may be affected by altering reaction conditions, for example pH or by adding a component so providing a means of controlling or tuning the position at which the equilibrium lies and controlling the level of binding or release of the catalyst.
- Examples of preferred groups G with substituents Q which may be in equilibrium between two forms. Where Q is OH, it is preferably located at the ortho position and linker group L comprises a group which is capable of reversibly forming a ring with the OH substituent, preferably L comprises a pendant acid or ester group CO2R where the OH substituent and acid or ester group may form a ring. Where Q is NR2, preferably NHR or NH2, this group may reversibly form an ammonium ion N+H3 or N+R3 by altering the pH, or to N(R)CO2H in the presence of free CO2. Substituent Q may be —OR, preferably —OCH3 and may be reversibly converted to —O+(R)—SiR3 in the presence of a trialkyl silane. Where substituent Q is CO2H, changing the pH may reversibly convert this group to a carbon/late anion. Where R is NH2, acetone or other carbonyl functionality may be added to derivatise the amine to the corresponding imines and for example in the case of acetone the reaction may be reversed by washing with water. By changing the reaction conditions, or introducing other components, group Q may exist in more than one form so enabling control of the position of the equilibrium.
- In a fifth aspect, the invention provides for use of a compound of formula I, preferably a compound of formula VI to selectively remove a component from a reaction medium so the component may be treated and subsequently return the component to the reaction medium.
- Suitably, the component to be removed from a reaction medium is one or more of a catalyst and unreacted feedstock. Unreacted feedstock typically is not subsequently returned to the reaction medium. In a preferred embodiment, the component to be removed comprises a metal with or without ancilliary ligands, more preferably a metal of Group 8, 9, 10 or 11 of the Periodic Table. Examples of preferred metals include palladium, platinum, rhodium, ruthenium, iridium, nickel, copper and iron, optionally comprising ancilliary ligands.
- In a sixth aspect, the invention comprises an organometallic species of a catalyst CAT and a compound of formula I, preferably a compound of formula VI wherein CAT comprises a metal with or without ancilliary ligands. The catalyst CAT preferably comprises palladium, platinum, rhodium, iridium, ruthenium, copper, nickel or iron, optionally comprising ancilliary ligands. The catalyst CAT is preferably bound to the compound I at group G which has a substituent Q and a leaving group LG as hereinbefore defined. Preferably the catalyst CAT is interposed between the aryl, heteroaryl or alkyl group of group G and leaving group LG as shown in formula VII below:
-
[SUP]-[L]-[G]-[CAT]-[LG] - The compound for treating the species of formula VII is suitably of formula R″″[MET]e[X″]f, (compound IV), as hereinbefore defined or a salt thereof, preferably an alkali metal salt M″X″, for example R″″B(OH)3 −K+) and after contacting with the compound of formula VII, the catalyst CAT is released into a reaction medium. Selectively removing the catalyst from the reaction medium allows feedstocks to be replenished or altered, impurities or by-products to be removed without the drawbacks associated with retaining a homogeneous catalyst in the reaction medium during such processing.
- The catalyst CAT is suitably employed in a homogeneously catalysed process for the formation of a new carbon carbon, carbon nitrogen, carbon oxygen or other carbon heteroatom bond through a homogeneously catalysed process in which the catalyst may be selectively removed and returned to the reaction, the process involving the addition of a catalyst to a compound of formula R″-LG, wherein LG is a leaving group as hereinbefore defined, to produce an organometallic species of formula VIII R″-CAT-LG, treating the compound VIII whereby LG is replaced by a group selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, or heterocyclic moiety to provide a species of formula IX R″-CAT-R″″ wherein R″ and R″″ are independently selected from aryl, heteroaryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, or heterocyclic moiety.
- The compound for treating the species of formula VIII is suitably of formula R″″[MET]e[X″]f as hereinbefore defined or a salt thereof and after contacting with the compound of formula VIII, the compound of formula IX and [MET]e[X″]f+1 is produced. The compound of formula IX may then be treated to release catalyst CAT into a reaction medium and to form compound R″-R″″. The catalyst may then suitably be recovered from the reaction medium by binding with a compound of formula I or VI, thereby allowing the reaction medium to be treated for example to remove by-products, unreacted reactants and the like or to allow new reactants to be introduced or to alter reaction conditions in the absence of the catalyst. The captured catalyst may then be returned to the reaction medium as required.
- Preferably LG is a halide or a pseudo halide as hereinbefore defined for example triflate, or under catalysis conditions with certain metals, an alkoxide, an ester and a nitrile.
- We have found that the organopolysiloxanes of the invention are especially suited to recovery of metal catalysts employed in a wide range of reactions in which an aryl, vinyl, heterocyclic or alkyl boronic acid is reacted with an aryl, benzyl, alkyl, vinyl, allyl, alkynyl, alkenyl, acyl, sulfonyl or heterocyclic halide or pseudo halide catalyzed by a metal catalyst.
- In a seventh aspect the invention provides a process for producing a reaction product by homogeneous catalysis comprising reacting a feedstock in the presence of a homogeneous catalyst in a reaction medium to produce directly or indirectly a reaction product, contacting the catalyst with a compound of formula I, preferably formula VI to remove the catalyst from the reaction medium to produce an organometallic species comprising the catalyst bound to the compound of formula I, preferably VI, treating the catalyst, returning the catalyst to the reaction medium and reacting a second feedstock in the presence of the returned homogeneous catalyst to produce a second reaction product or a second batch of the same reaction product.
- The first and second feedstocks may be the same or different. For pharmaceutical preparation processes, the first and any subsequent feedstocks are advantageously the same, for regulatory reasons. With appropriate analysis and quality control, different feedstocks may be employed. Removal of the catalyst allows the catalyst life to be extended and the compound of formula I beneficially purifies the reaction product by removing excess feedstock as well as the catalyst to be regenerated from the reaction medium. The catalyst upon removal from the reaction medium is temporarily in heterogeneous form and is suitably released into the reaction medium by contact of the bound catalyst with the second feedstock.
- The process of removing the catalyst from a reaction medium to form an organometallic species treating the species and reintroducing the catalyst into the same or a different reaction medium may be repeated as desired.
- The process allows removal of excess reagent thereby improving product isolation.
- In a further preferred aspect the invention provides a process for producing a reaction product comprising a coupled biaryl, aryl-heteroaryl, aryl-alkyl, heteroaryl-alkyl, biheteroaryl, bialkyl reaction product by homogeneous catalysis comprising reacting a feedstock comprising a compound of formula R″″[MET]e[X″]f or R″″[MET]e[X″]f − M″+ with a compound of formula R″Br in the presence of a homogeneous catalyst comprising a metal in a reaction medium to produce a coupled biaryl product of formula R″-R″″, contacting the catalyst with a compound of formula I, preferably a compound of formula VI
- as defined above to remove the catalyst from the reaction medium, treating the catalyst by contacting with a compound of formula R″″[MET]e[X″]f as hereinbefore defined to return it to the reaction medium and contacting the returned metal catalyst with a further feedstock to effect a further reaction to produce a second reaction product.
- Suitably the catalyst may comprise any metal suitable for the reaction being carried out. Examples of suitable catalysts for treatment according to methods of the invention include Pt, Pd, Ni, Fe, Cu, Ir, Ru, Rh. The invention enables a metal catalyst to be removed from and reintroduced to a reaction medium together with any associated ancilliary ligands that may be present.
- Suitably the catalyst may comprise Pd, Ni and Fe, especially for Suzuki reactions, Pd, Cu, Ni and Fe for formation of C—N and C—O bonds, Pd, Ni, Fe, Cu, Ir, Ru, Rh for formation of a C—C bond. Examples of suitable palladium catalysts include palladium combined with a phosphine including monodentate and bidentatephosphines, a phosphite, a phosphoramidite, a carbene, ligands containing nitrogen and ligands containing oxygen, and any combination of two or more of these groups. Examples of specific palladium catalysts include palladium acetate, bis(triphenylphosphine) palladium chloride or acetate and tetrakis(triphenylphosphine)palladium(0), include tris-dibenzylideneacetone di-palladium(0) plus other palladium ligand salts plus other metals.
- The present invention enables catalysts to be removed from a wide-range of catalyzed reactions including alpha arylation (metal enolate), amidation, amination, etherification, esterification, cyanation (cyanide ion), and carbonylation reactions. Examples of particular reactions in which the present invention may be employed for catalyst removal and reintroduction include Miyaura borylation (pinacol borylation), Buchwald Hartwig amination (primary or secondary amine), Ullman etherification, Ullmann amination (Goldberg reaction), carbonylation for hydroformylation, ester, acid, amide and diketone formation, Chan Lam amination, Mizoroki Heck reaction (alkene), Sonogashira reaction (alkyne), Hiyama reaction (ArSi), Kumada Corriu reaction, Negishi reaction, reductive Heck Reaction, Tsuji Trost reaction (enolate), Stille reaction and Suzuki Miyaura reaction.
- The process for producing a reaction product may be carried out in a batch process although a continuous process may be employed. Suitably the catalyst and feedstocks are fed to a reaction zone. The compound of the invention is suitably located in a separate bed, for example a conventional cartridge arrangement, in a recycle loop around the reaction zone. The reaction is carried out in the reaction zone, the reaction mixture is then passed through the separate bed and contacted with the compound of the invention. The catalyst and, as desired unreacted feedstocks are bound in the bed and the reaction mixture depleted in these components is fed elsewhere. A new feedstock, comprising the same or different components to those previously employed or coupling partner is then passed through the bed and releases the catalyst from the bed and is carried back to the reaction zone where the second or subsequent reaction is carried out.
- Where compound I or VI comprises a silica or alumina support, silicas and aluminas suitable for functionalization to produce a compound of formula I or VI include any silica or alumina having surface Si(OH) or Al(OH) moieties respectively. The silica or alumina may be produced by treating a commercially available silica or alumina with alkenyl trialkoxysilane, for example vinyl trimethoxy silane available from Sigma Aldrich (cat no. 235768). Sulphur-linked compounds may be produced by treating with a thiol under radical generating conditions to afford a sulphur-linked compound of formula I or VI. A functionalised trialkoxysilane may be produced by reacting with a species to produce the desired functional group and which is then coated on or reacted with an existing support of silica or alumina.
- Where compound I or VI comprises a polymer, for example polystyrene support, copolymerisation of a commercially available functionalised monomer for example a functionalised styrene with a monomer, for example styrene, with or without copolymer additives, using standard techniques affords the functionalised polymer support. Alternatively functionalization of a pre-formed polymer may also be employed using conventional methods.
- The invention is now illustrated by the following illustrative examples.
-
- Cysteamine hydrochloride (193.10 g, 1.7 mol) was stirred and heated to 120° C. When the material had become molten, vinyl trimethoxysilane (229.95 g, 1.55 mol) and tert-butyl peroxide (2.0 mL, 10.89 mmol) was added over 30 min. The heterogeneous mixture was heated at 120-130° C. for a further hour, before a second addition of tert-butyl peroxide (2.0 mL, 10.9 mmol). The reaction mixture was stirred for 2 hours at this temperature whereupon the solution had become homogeneous. The solution was then cooled to room temperature to provide a crude product.
- A mixture of this crude product above, silica (1.00 kg, 70-230 mesh) and toluene (2.5 L) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene, methanol and water before being dried on the sinter funnel until mobile. A mixture of the semi-dried material and water (2 L) was stirred and a pH probe was carefully immersed in the solution. Sodium hydroxide solution (853 mL, 1.5 M) was added over 10 minutes. The solution pH was monitored during the addition and requires an end-point of pH 8.8-9.2. The mixture is stirred for a further 20 minutes then filtered, washed with water and methanol and dried in a vacuum oven. The structure was verified by NMR techniques.
- A mixture of 4-bromobenzoic acid (1.2 g, 6 mmol, 1.05 eq. based on functional group (FG) loading and DMF (15 mL) was stirred for 5 min at room temperature to afford a colourless solution. Diisopropylamine (1.05 eq. based on FG loading) followed by 0-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.6 g, 6 mmol, 1.05 eq. based on FG loading) are added at 5 min intervals with continual stirring. After a further 5 min, the product from above (5.0 g) is added and stirring continued for 1 h, whereupon the reaction mixture is filtered and washed with methanol, 1 M aqueous Na2CO3, water and methanol and dried. The structure was verified by NMR techniques.
-
- Silica (50 g, 70-200 micron, 60 Å), 3-aminopropyl trimethoxysilane (11.2 g, 62.5 mmol) and toluene (140 mL) were heated at reflux for 4 h. The reaction was then allowed to cool and was filtered. The solid was washed with methanol and dried in a vacuum oven.
- 4-Bromobenzoic acid (1.21 g, 6 mmol) and DMF (15 mL) were stirred for 5 minutes at room temperature to afford a colourless solution. Diisopropylamine (1.58 g, 6 mmol) followed by O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.28 g, 6 mmol) were added at 5 min intervals with continual stirring. After a further 5 min 3-aminopropyl functionalised silica (from above) (5.00 g, 1.25 mmol/g functional group loading) is added and stirring continued for 1 h whereupon the reaction mixture is filtered and the silica washed with methanol, water, 1 M aqueous Na2CO3, water and methanol and dried in a vacuum oven. The structure was verified by NMR techniques.
-
- A solution of benzoic acid (2.11 g, 10.5 mmol) and DMF (25 mL) was stirred at room temperature for 5 min. Triethylamine (2.00 g, 20.0 mmol) was added and the stirring continued at room temperature, after 5 min HBTU (3.98 g, 10.5 mmol) was added, followed 5 min later by aminopropyl trimethoxysilane (1.79 g, 10.0 mmol). The reaction mixture was shaken at room temperature for a further 1 h.
- A mixture of the crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of bromophenyltrimethoxysilane (1.00 g, 3.6 mmol), silica (5.00 g, 70-230) and toluene (20 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and before being dried. The structure was verified by NMR techniques.
-
- A mixture of trimethoxyvinylsilane (1.48 g, 10.0 mmol), 4-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 4-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- A mixture of the crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- Mercaptosuccinic acid (99.87 g, 0.67 mol) was heated until an internal pot temperature of 80° C. is reached, then a solution of vinyl trimethoxysilane (81.34 g, 0.59 mol) and di tert butyl peroxide (1.74 mL, 9.5 mmol) was added dropwise. The mixture was heated for a further 2 hours, reaching a temperature of 105° C. A further addition of di tert butyl peroxide (1.74 mL, 9.5 mmol) was made and the mixture refluxed for a further hour. Once satisfied (by proton NMR sample analysis) that the reaction was complete, methanol (120 mL) was added and the material cooled to room temperature.
- Silica (0.38 kg, 70-200 μm, 60 Å) toluene (1.0 L) and material from Step 1 (0.59 mol) were heated at reflux for 4 h. The reaction was then allowed to cool and the solid material was washed with methanol, sodium hydroxide, water and methanol and then dried on the sinter funnel until mobile.
- 3-Bromobenzylamine hydrochloride (8.90 g, 40 mmol), aqueous sodium carbonate solution (50 mL, 1 M) and toluene (50 mL) were stirred and heated to approx. 100° C. for 1 h (or until all solid has dissolved) whereupon the mixture was allowed to cool and the phases separated. The organic phase was then added to a mixture of succinic acid ethyl sulphide silica (29 g, 1.4 mmol/g loading), methane sulfonic acid (0.19 g, 2 mmol) and toluene (50 mL). The resultant mixture was heated at reflux under Dean-Stark conditions for 4 h before being allowed to cool. The solid was filtered and washed with toluene and methanol and dried in a vacuum oven. The structure was verified by NMR techniques.
-
- A mixture of trimethoxyvinylsilane (1.48 g, 10.0 mmol), 2-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 2-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of trimethoxyvinylsilane (1.48 g, 10.0 mmol), 3-bromothiophenol (2.27 g, 12.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 3-bromothiophenol (1.14 g, 6.0 mmol) being added after 3 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of trimethoxyvinylsilane (1.48 g, 10.0 mmol), 4-chlorothiophenol (2.17 g, 15.0 mmol), AlBN (0.08 g) and toluene (10 mL) was heated to 50° C. The temperature was maintained for 6 h, with AlBN (0.08 g) being added hourly and further 4-chlorothiophenol (1.00 g, 7.0 mmol) being added after 3 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of the product from Example 4 (1.00 g) and DCM (14 mL) was cooled in an ice-bath and mCPBA (1.0 eq. based on FG loading) was added with stirring. The mixture was allowed to warm to room temperature over 2 h before being filtered and washed with toluene and methanol and then dried. The structure was verified by NMR techniques.
-
- A mixture of the product from Example 4 (5.00 g) and DCM (14 mL) was cooled in an ice-bath and mCPBA (4.0 eq. based on FG loading) was added with stirring. The mixture was allowed to warm to room temperature over 2 h before being filtered and washed with toluene and methanol and then dried. The structure was verified by NMR techniques.
-
- A mixture of chloropropyl trimethoxysilane (1.99 g, 10.0 mmol), 4-bromo-N-methyl aniline (4.65 g, 25.0 mmol), sodium bromide (1.13 g, 11.0 mmol) and DMF (10 mL) was heated to 100° C. and stirred at that temperature for 17.5 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of 4-bromobenzoic acid (4.02 g, 20.0 mmol), cesium carbonate (3.26 g, 10.0 mmol) and DMF (10 mL) was heated to 50° C. for and stirred for 30 min. Sodium bromide (1.23 g, 12.0 mmol), chloropropyltrimethoxysilane (1.99 g, 10.0 mmol) and DMF (10 mL) were then added and the resultant mixture heated at 80° C. for 16 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with water and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of trimethoxy(2-phenylethyl)silane (0.50 g, 2.2 mmol) and DCM (5 mL) was cooled in an ice bath and bromine (1.40 g, 8.8 mmol) was added dropwise. The resultant mixture was stirred and allowed to warm to room temperature over 1 h before being diluted with DCM (5 mL) and partitioned with aqueous Na2S2O7 solution (10 mL, 1 M). The organic phase was separated and washed with water (10 mL) and brine (20 mL), toluene (10 mL) was then added and the DCM removed in vacuo.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of chloropropyl trimethoxysilane (1.99 g, 10.0 mmol), sodium iodide (1.80 g, 12.0 mmol) and DMF (10 mL) was heated to 50° C. for 1.5 h. 4-Bromophenol (5.19 g, 30.0 mmol), potassium carbonate (2.07 g, 15.0 mmol) and DMF (10 mL) were then added and the resultant mixture heated at 80° C. for 22.5 h.
- A mixture of the resulting crude product above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with water and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of the product from Example 4, trimethoxypropyl silane (1.0 mmol/g silica input) and toluene (3.5 mL/g silica, or minimum 50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with toluene and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of chloropropyl trimethoxysilane (1.99 g, 10.0 mmol), phthalimide (3.68 g, 25.0 mmol), caesium carbonate (3.58 g, 11.0 mmol), sodium bromide (1.13 g, 11.0 mmol) and DMF (10 mL) was stirred and heated to 55° C. for 16 h.
- A mixture of the resulting crude product from above, silica (10.00 g, 70-230 mesh) and toluene (50 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with water and methanol before being dried. The structure was verified by NMR techniques.
- A mixture of the product from above (6.00 g) and DCM (30 mL) was cooled to 0° C. and bromine (1.0 eq. based on FG loading) added dropwise. The reaction mixture was allowed to warm to room temperature over 4 h before being filtered and washed with DCM, water and methanol before being dried. The structure was verified by NMR techniques.
-
- A mixture of chloropropyl trimethoxysilane (3.62 g, 18.0 mmol), thiophenol (5.75 g, 46.0 mmol), sodium bromide (2.06 g, 20.0 mmol), potassium carbonate (3.78 g, 27.0 mmol) and DMF (18 mL) was stirred and heated to 100° C. for 18 h.
- A mixture of the resulting crude product from above, silica (22.00 g, 70-230 mesh) and toluene (80 mL) was heated at reflux for 4 h. After cooling, the reaction mixture was filtered and washed with water and methanol before being dried. The structure was verified by NMR techniques.
- A mixture of the product from above (8.00 g), 4-nitrophenyl trifluoromethanesulfonate (1.0 eq. based on FG loading), potassium carbonate (1.0 eq. based on FG loading) and DMF (25 mL) was stirred at room temperature for 4 h before being filtered and washed with water and methanol before being dried. The structure was verified by NMR techniques.
- A sample of Palladium (bis(di-tert-butylphosphin)ferrocene)dichloride (1 mmol) was dispensed to a reaction tube. Phenyl boronic acid (3 mmol) and potassium carbonate (3 mmol) were added. The supported Aryl Br produced in Example 3 was added (5 mmol). Acetonitrile (20 rel volumes) and water (5 rel volumes) were added to the reaction mixture. The reaction was stirred and heated to 60° C. The reaction was analysed by GCMS after 1 h showing complete consumption of phenylboronic acid. The supported Aryl Br contained the colour and the solvent was a very light yellow colour. The catalyst is coloured and the colour comes out of solution onto the supported aryl bromide. Upon washing the support, catalyst is released and the support is usable in a new reaction.
- A sample of Palladium (bis(di-tert-butylphosphin)ferrocene)dichloride (0.05 mmol) was dispensed to a reaction tube. 4-Bromobenzonitrile (1 mmol), phenyl boronic acid (1.1 mmol) and potassium carbonate (1.1 mmol) were added. Acetonitrile (5 rel volumes) and water (5 rel volumes) were added to the reaction mixture. The reaction was stirred and heated to 60° C. The reaction was analysed by GCMS after 18 h showing complete consumption of 4-bromobenzonitrile. The supported Aryl Br produced in Example 3 was added (0.5 mmol) and the mixture stirred at 60° C. overnight. The supported Aryl Br contained the colour and the solvent was a very light yellow colour.
- 4-Bromobenzonitrile (1 mmol), phenyl boronic acid (1.1 mmol) and potassium carbonate (1.1 mmol) were added to a reaction tube. Acetonitrile (5 rel volumes) and water (5 rel volumes) were added to the reaction mixture. The supported aryl bromide produced in Example 18 with attached Pd ligand organometallic species was added to the reaction. The reaction was stirred and heated to 60° C. The reaction was analysed by GCMS after 18 h showing complete consumption of 4-bromobenzonitrile. The supported Aryl Br was added (0.5 mmol) and the mixture stirred at 60° C. overnight. The supported Aryl Br contained the colour and the solvent was a very light yellow colour, the catalyst being coloured. The support may be washed to release the catalyst and then reused as desired.
Claims (30)
[SUP][[L]-[G]]n (I)
[(O3/2)Si[L]G]a[Si(O4/2)]b[Si(O3/2)V′]c (VI)
[SUP]-L-G-CAT-LG (VII)
R″-LG (II)
R″-CAT-LG (III);
R″″[MET]e[X″]f (IV)
R″-R″″ (VIII)
[SUP]-[G]n′ (IA)
[SUP]-G-CAT-LG (VII)
R″-LG (II)
R″-CAT-LG (III);
R″″[MET]e[X″]f (IV)
R″-R″″ (VIII)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16/707,816 US20200255457A1 (en) | 2012-11-28 | 2019-12-09 | Process for the removal and return of a catalyst to a liquid phase medium |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1221402.9A GB2508350A (en) | 2012-11-28 | 2012-11-28 | A process for the selective removal of a catalyst from a liquid phase |
GB1221402.9 | 2012-11-28 | ||
PCT/EP2013/074974 WO2014083109A2 (en) | 2012-11-28 | 2013-11-28 | Process for the removal and return of a catalyst to a liquid phase medium |
US201514647919A | 2015-06-12 | 2015-06-12 | |
US16/707,816 US20200255457A1 (en) | 2012-11-28 | 2019-12-09 | Process for the removal and return of a catalyst to a liquid phase medium |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/647,919 Continuation US10519173B2 (en) | 2012-11-28 | 2013-11-28 | Process for the removal and return of a catalyst to a liquid phase medium |
PCT/EP2013/074974 Continuation WO2014083109A2 (en) | 2012-11-28 | 2013-11-28 | Process for the removal and return of a catalyst to a liquid phase medium |
Publications (1)
Publication Number | Publication Date |
---|---|
US20200255457A1 true US20200255457A1 (en) | 2020-08-13 |
Family
ID=47560816
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/647,919 Active US10519173B2 (en) | 2012-11-28 | 2013-11-28 | Process for the removal and return of a catalyst to a liquid phase medium |
US16/707,816 Pending US20200255457A1 (en) | 2012-11-28 | 2019-12-09 | Process for the removal and return of a catalyst to a liquid phase medium |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/647,919 Active US10519173B2 (en) | 2012-11-28 | 2013-11-28 | Process for the removal and return of a catalyst to a liquid phase medium |
Country Status (6)
Country | Link |
---|---|
US (2) | US10519173B2 (en) |
EP (1) | EP2925438A2 (en) |
JP (1) | JP6310475B2 (en) |
CN (1) | CN104884506B (en) |
GB (2) | GB2508350A (en) |
WO (2) | WO2014083109A2 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016208320A1 (en) * | 2015-06-24 | 2016-12-29 | 日本ゼオン株式会社 | Method for recovering catalyst |
CN113797978B (en) * | 2021-10-12 | 2023-11-07 | 青岛科技大学 | Preparation method and application of poly (triarylphosphine oxide) -supported palladium/copper bimetallic catalyst |
CN115805102B (en) * | 2022-11-25 | 2024-04-05 | 中科合成油技术股份有限公司 | Heterogeneous catalyst for preparing high-carbon aldehyde by hydroformylation of medium-long chain alpha-olefin and preparation method thereof |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4032597A1 (en) * | 1990-10-13 | 1992-04-16 | Bayer Ag | RECOVERY OF HYDRATION CATALYSTS FROM SOLUTIONS OF HYDRATED NITRILE RUBBER |
US7264728B2 (en) * | 2002-10-01 | 2007-09-04 | Dow Corning Corporation | Method of separating components in a sample using silane-treated silica filter media |
GB0417344D0 (en) * | 2004-08-04 | 2004-09-08 | Phosphonics Ltd | Substituted organopolysiloxanes and use thereof |
DE602005011308D1 (en) | 2004-08-04 | 2009-01-08 | Phosphonics Ltd | SUBSTITUTED ORGANOPOLYSILOXANES AND THEIR USE |
GB0417345D0 (en) * | 2004-08-04 | 2004-09-08 | Phosphonics Ltd | Substituted organopolysiloxanes and uses thereof |
GB0514502D0 (en) * | 2005-07-14 | 2005-08-24 | Phosphonics Ltd | Substituted organopolysiloxanes containing phosphonic groups,method for the production and use thereof |
GB0602811D0 (en) * | 2006-02-10 | 2006-03-22 | Phosphonics Ltd | Substituted Organopolysiloxanes And Use Thereof |
GB0720579D0 (en) * | 2007-10-20 | 2007-11-28 | Phosphonics Ltd | Functionalised materials and uses thereof |
JP5387228B2 (en) * | 2009-08-21 | 2014-01-15 | 東ソー株式会社 | Method for removing dissolved palladium |
GB201006368D0 (en) * | 2010-04-15 | 2010-06-02 | Phosphonics Ltd | Functionalised materials and uses thereof |
GB201100531D0 (en) * | 2011-01-13 | 2011-03-02 | Phosphonics | Functionalised materials, processes for the production and uses thereof |
-
2012
- 2012-11-28 GB GB1221402.9A patent/GB2508350A/en not_active Withdrawn
-
2013
- 2013-11-28 GB GB1511333.5A patent/GB2528778B/en active Active
- 2013-11-28 US US14/647,919 patent/US10519173B2/en active Active
- 2013-11-28 JP JP2015544460A patent/JP6310475B2/en active Active
- 2013-11-28 EP EP13824490.0A patent/EP2925438A2/en active Pending
- 2013-11-28 CN CN201380067936.XA patent/CN104884506B/en active Active
- 2013-11-28 WO PCT/EP2013/074974 patent/WO2014083109A2/en active Application Filing
- 2013-11-28 WO PCT/EP2013/074984 patent/WO2014083112A1/en active Application Filing
-
2019
- 2019-12-09 US US16/707,816 patent/US20200255457A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
JP2016501717A (en) | 2016-01-21 |
GB201511333D0 (en) | 2015-08-12 |
GB2508350A (en) | 2014-06-04 |
WO2014083112A1 (en) | 2014-06-05 |
WO2014083109A3 (en) | 2014-11-20 |
CN104884506B (en) | 2021-10-19 |
GB201221402D0 (en) | 2013-01-09 |
JP6310475B2 (en) | 2018-04-11 |
WO2014083109A2 (en) | 2014-06-05 |
CN104884506A (en) | 2015-09-02 |
GB2528778A (en) | 2016-02-03 |
GB2528778B (en) | 2018-04-11 |
EP2925438A2 (en) | 2015-10-07 |
US10519173B2 (en) | 2019-12-31 |
US20150299229A1 (en) | 2015-10-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200255457A1 (en) | Process for the removal and return of a catalyst to a liquid phase medium | |
JP4964772B2 (en) | Substituted organopolysiloxanes and their use | |
Okamoto et al. | Suzuki− Miyaura Coupling Catalyzed by Polymer-Incarcerated Palladium, a Highly Active, Recoverable, and Reusable Pd Catalyst | |
Alvaro et al. | Resting state and elementary steps of the coupling of aryl halides with thiols catalyzed by alkylbisphosphine complexes of palladium | |
JP5449782B2 (en) | Substituted organopolysiloxane and use thereof | |
US7250510B2 (en) | Transition metal complexes of N-heterocyclic carbenes, method of preparation and use in transition metal catalyzed organic transformations | |
CN101023120B (en) | Substituted organopolysiloxanes and use thereof | |
Yang et al. | Highly stereoselective anti-Markovnikov hydrothiolation of alkynes and electron-deficient alkenes by a supported Cu-NHC complex | |
Bismuto et al. | Nickel-Catalyzed Amination of Aryl Thioethers: A Combined Synthetic and Mechanistic Study | |
Remmele et al. | Recyclable catalyst with cationic phase tags for the Sonogashira coupling of aryl bromides and aryl chlorides | |
JP2008508406A5 (en) | ||
US20190176124A1 (en) | Polyorganic functional groups modified silica, processes to make and use thereof | |
IT8224869A1 (en) | RECOVERY OF TRIARILBORANS | |
US20110172432A1 (en) | Method for the synthesis of heterogeneous palladium catalysts, catalysts obtained and use of same | |
Daly et al. | Copper (I) diphosphine catalysts for C− N bond formation: Synthesis, structure, and ligand effects | |
JP2016501717A5 (en) | ||
JP4114262B2 (en) | Ferrocenylaminophosphine and catalyst containing the phosphine | |
Vicente et al. | Synthesis of Mono-, Di-, and Tripalladated 1, 3, 5-Benzenetricarboxaldehyde Complexes | |
JP6123294B2 (en) | Method for producing palladium separating agent | |
JP4601864B2 (en) | Method for separating palladium-containing compounds | |
Rajmane et al. | Applications of NS ligands for palladium-catalysed cross-coupling reactions | |
JP5125008B2 (en) | Process for producing biaryl compounds | |
Agniparthi | Solid-phase organic synthesis of 4-alkenyl-1-naphthols | |
JP2004501877A (en) | Catalysis using phosphine oxide compounds and sulfoxide compounds | |
Alfahd | Synthesis of Ni (dppe) 2 and Nickel (I) Catalysts and their Ability to Catalyzed Cross-Coupling |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |