WO2022252404A1 - Réactif de radicaux libres fluorosulfonyle et procédé de préparation associé et son utilisation - Google Patents
Réactif de radicaux libres fluorosulfonyle et procédé de préparation associé et son utilisation Download PDFInfo
- Publication number
- WO2022252404A1 WO2022252404A1 PCT/CN2021/113240 CN2021113240W WO2022252404A1 WO 2022252404 A1 WO2022252404 A1 WO 2022252404A1 CN 2021113240 W CN2021113240 W CN 2021113240W WO 2022252404 A1 WO2022252404 A1 WO 2022252404A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- fluorosulfonyl
- formula
- substituted
- group
- reaction
- Prior art date
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- -1 Fluorosulfonyl free radical Chemical class 0.000 title claims abstract description 133
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 114
- 238000002360 preparation method Methods 0.000 title claims abstract description 35
- 239000000758 substrate Substances 0.000 claims abstract description 45
- 238000007348 radical reaction Methods 0.000 claims abstract description 23
- 150000001336 alkenes Chemical class 0.000 claims abstract description 6
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 5
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 83
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 238000006243 chemical reaction Methods 0.000 claims description 64
- 125000001624 naphthyl group Chemical group 0.000 claims description 48
- 239000003960 organic solvent Substances 0.000 claims description 45
- 239000013067 intermediate product Substances 0.000 claims description 44
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- 235000010290 biphenyl Nutrition 0.000 claims description 42
- 239000004305 biphenyl Substances 0.000 claims description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- 239000002994 raw material Substances 0.000 claims description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
- 239000000047 product Substances 0.000 claims description 34
- 230000002950 deficient Effects 0.000 claims description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 238000007350 electrophilic reaction Methods 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 24
- OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 claims description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 15
- 239000005935 Sulfuryl fluoride Substances 0.000 claims description 15
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 15
- 150000001450 anions Chemical class 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 12
- 150000001768 cations Chemical class 0.000 claims description 11
- 238000005349 anion exchange Methods 0.000 claims description 10
- 239000003504 photosensitizing agent Substances 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000011941 photocatalyst Substances 0.000 claims description 8
- 150000007529 inorganic bases Chemical class 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- 229910017008 AsF 6 Inorganic materials 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 235000011181 potassium carbonates Nutrition 0.000 claims description 6
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 6
- 235000011009 potassium phosphates Nutrition 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 239000012312 sodium hydride Substances 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 125000006267 biphenyl group Chemical group 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 150000004696 coordination complex Chemical class 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000005577 anthracene group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical group C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
- 150000003457 sulfones Chemical class 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 15
- 150000003254 radicals Chemical class 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract 1
- 231100000419 toxicity Toxicity 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 17
- 239000002904 solvent Substances 0.000 description 11
- 239000007789 gas Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 239000012043 crude product Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 238000002390 rotary evaporation Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- DWYHDSLIWMUSOO-UHFFFAOYSA-N 2-phenyl-1h-benzimidazole Chemical compound C1=CC=CC=C1C1=NC2=CC=CC=C2N1 DWYHDSLIWMUSOO-UHFFFAOYSA-N 0.000 description 2
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical group C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 2
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- UUPCJAJKSFQJCI-UHFFFAOYSA-N O=S(N1C(C2=CC=CC=C2)=NC2=C1C=CC=C2)(F)=O Chemical compound O=S(N1C(C2=CC=CC=C2)=NC2=C1C=CC=C2)(F)=O UUPCJAJKSFQJCI-UHFFFAOYSA-N 0.000 description 2
- YBKTUHZNXISZHE-UHFFFAOYSA-N O=S(N1C(C2=CC=CC=C2)=NC=C1)(F)=O Chemical compound O=S(N1C(C2=CC=CC=C2)=NC=C1)(F)=O YBKTUHZNXISZHE-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 description 1
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- MKYQPGPNVYRMHI-UHFFFAOYSA-N Triphenylethylene Chemical group C=1C=CC=CC=1C=C(C=1C=CC=CC=1)C1=CC=CC=C1 MKYQPGPNVYRMHI-UHFFFAOYSA-N 0.000 description 1
- HXELGNKCCDGMMN-UHFFFAOYSA-N [F].[Cl] Chemical group [F].[Cl] HXELGNKCCDGMMN-UHFFFAOYSA-N 0.000 description 1
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- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
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- 238000001816 cooling Methods 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- IXPAAHZTOUOJJM-UHFFFAOYSA-N sulfuryl chloride fluoride Chemical compound FS(Cl)(=O)=O IXPAAHZTOUOJJM-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/22—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms directly attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
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- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
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- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Definitions
- the invention relates to the technical field of organic synthesis, in particular to a fluorosulfonyl free radical reagent and its preparation method and application.
- Sulfonyl fluoride compounds as the most important class of compounds containing hexavalent sulfur-fluorine bonds, have attracted extensive attention from materials, chemistry and biologists.
- the fluorine-chlorine exchange reaction is an important method for the synthesis of sulfonyl fluoride compounds, but this method has limited its wide application due to the lack of stability, applicability and substrate source limitations (Angew.Chem.Int . Ed. 2014, 53, 9430).
- alkenylsulfonyl fluoride can obtain sulfonyl fluoride products through nucleophilic addition, free radical addition or Diels-Alder reaction (J.Org.Chem.1979,44,3847; Angew. Chem.Int.Ed.2009,48,9879; Nat.Commun.2019,10,3752), but the structure of the sulfonyl fluoride product obtained by this method is relatively simple.
- the object of the present invention is to provide a fluorosulfonyl free radical reagent and its preparation method and application.
- the fluorosulfonyl free radical reagent provided by the present invention can efficiently generate fluorosulfonyl free radicals and undergo corresponding free radical reactions.
- the present invention provides a fluorosulfonyl radical reagent, including a cation and an anion, and the cation has a structure shown in formula I-1 or formula I-2:
- R 1 and R 2 are independently hydrogen or an alkyl group
- R 3 is an alkyl group
- Ar 1 and Ar 2 are independently an aromatic ring or a substituted aromatic ring;
- the anion is - BF 4 , - BF 6 , - PF 6 , - PF 4 , - SbF 6 , - NTf 2 or - AsF 6 .
- the aromatic ring is a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring
- the substituent in the substituted aromatic ring is an alkyl group or an electron-deficient group.
- the electron deficient group includes -F, -Cl, -Br, trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl or alkylsulfonyl Acyl.
- the number of carbon atoms in the alkyl group is 1-8.
- the cation of the fluorosulfonyl radical reagent is any one of the compounds shown in formula 1 to formula 9:
- R 1 and R 2 are independently hydrogen or alkyl
- R 3 is alkyl
- R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 and R 32 are independently hydrogen, alkyl or electron deficient group.
- the fluorosulfonyl radical reagent is N-(2-aminoethyl)-2-aminoethyl radical reagent
- the present invention provides a preparation method of the fluorosulfonyl free radical reagent described in the above technical scheme, comprising the following steps:
- the preparation method comprises the following steps:
- the first raw material has a structure shown in formula II-1 or formula II-2
- the first intermediate product has a structure shown in formula III-1 or formula III-2:
- the second raw material is R 3 OTf, R 3 OSO 2 F or R 3 HSO 4 ;
- the preparation method includes the following steps:
- the third raw material is AgBF 4 , AgBF 6 , AgPF 6 , AgPF 4 , AgSbF 6 , AgNTf 2 or AgAsF 6 .
- the alkaline reagent includes an inorganic base reagent or an organic base reagent
- the inorganic base includes sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, potassium phosphate, One or more of potassium tert-butoxide, sodium methoxide, sodium ethoxide and sodium hydride
- the organic base includes one or more of triethylamine, N,N-diisopropylethylamine, pyrrole and pyridine kind
- the molar ratio of the first raw material, sulfuryl fluoride and alkaline reagent is 6:(7-7.5):(7-16).
- the organic solvent added during the nucleophilic substitution reaction includes acetonitrile, dichloromethane, ethyl acetate, benzene, toluene, acetone, 1,4-dioxane, ether, tetrahydrofuran, 1,2-bis One or more of ethyl chloride, dimethyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, methyl tert-butyl ether and chloroform.
- the molar ratio of the first intermediate product to the second raw material is 1:(1.1-2.0).
- the organic solvents acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide added during the first electrophilic reaction
- One or more of , methyl tert-butyl ether and chloroform One or more of , methyl tert-butyl ether and chloroform.
- the temperature of the nucleophilic substitution reaction is -50-100°C, and the time is 1-48h; the temperature of the first electrophilic reaction is -50-100°C, and the time is 1-48h.
- the molar ratio of the first intermediate product to methyl iodide is 1:(1.05-5.0).
- the organic solvent added during the second electrophilic reaction includes tetrahydrofuran or acetonitrile.
- the molar ratio of the second intermediate product to the third raw material is 1:(1.05-5.0).
- the organic solvent added during the anion exchange reaction includes tetrahydrofuran or acetonitrile.
- the temperature of the second electrophilic reaction is -50-200°C, and the time is 1-48h; the temperature of the anion exchange reaction is -50-100°C, and the time is 1-48h.
- the present invention provides the application of the fluorosulfonyl radical reagent described in the above technical scheme in the fluorosulfonyl radical reaction.
- the application includes the following steps:
- reaction substrate fluorosulfonyl radical reagent, photosensitizer and organic solvent are mixed, and the fluorosulfonyl radical reaction is carried out under the irradiation conditions of ultraviolet light, blue light or visible light to obtain a fluorosulfonylated product;
- the reaction substrate includes alkenes or alkynes.
- the olefin compound has formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV-7, formula IV-8 or formula IV
- formula IV-1 formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV-7, formula IV-8 or formula IV
- formula IV-8 formula IV
- R includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl
- the substituent independently includes an alkyl group, an electron-rich group or an electron-poor group, and the electron-rich group is methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethylamino, methyl Thio or ethylthio;
- R 2 includes phenyl, substituted phenyl, ester group or carbonyl
- R 3 includes hydrogen, phenyl or substituted phenyl
- R 4 includes hydrogen, alkyl, phenyl or substituted phenyl
- the substituent in the substituted phenyl group includes an alkyl group, an electron-rich group or an electron-deficient group
- R includes hydrogen or alkyl
- Ar includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and the substituted phenyl, substituted naphthyl and the substituents in the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;
- R 6 includes hydrogen, alkyl, phenyl or acyl, and n is 1 or 2;
- X is O or S, and R 7 includes hydrogen, alkyl, phenyl or acyl;
- R and R independently include alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl, substituted biphenyl or acyl, and the substituted phenyl,
- the substituents in the substituted naphthyl and the substituted biphenyl independently include an alkyl group, an electron-rich group or an electron-deficient group;
- Ar includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and the substitution in the substituted phenyl, substituted naphthyl and substituted biphenyl
- the groups independently include alkyl groups, electron rich groups or electron deficient groups
- R 10 , R 11 , R 12 and R 13 independently include hydrogen, alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl Or a substituted biphenyl group, the substituents in the substituted phenyl group, substituted naphthyl group and substituted biphenyl group independently include an alkyl group, an electron-rich group or an electron-deficient group.
- the photosensitizer includes a metal complex photocatalyst or an organic photocatalyst.
- the molar ratio of the reaction substrate to the fluorosulfonyl radical reagent is 0.1: (0.15-0.4).
- the molar ratio of the reaction substrate to the photosensitizer is 0.1:(0.001-0.01).
- the fluorosulfonyl radical reaction is carried out in the presence of an inorganic alkaline reagent.
- the inorganic alkaline reagent includes one or more of potassium carbonate, sodium carbonate, potassium phosphate and sodium bicarbonate.
- the molar ratio of the reaction substrate to the inorganic alkali reagent is 0.1: (0.1-0.3).
- the temperature of the fluorosulfonyl radical reaction is -60-100° C., and the time is 1-72 h.
- the present invention provides a fluorosulfonyl radical reagent, which includes a cation and an anion, and the cation has the structure shown in formula I-1 or formula I-2.
- the fluorosulfonyl free radical reagent provided by the present invention can efficiently generate fluorosulfonyl free radicals and undergo corresponding free radical reactions, and the product yield is high; and the substrate adaptability of the fluorosulfonyl free radical reagent provided by the present invention is extremely wide, It can react with various types of olefin substrates and alkyne substrates to efficiently synthesize fluorosulfonylated products; at the same time, the fluorosulfonyl free radical reagent provided by the invention is a stable solid state at room temperature, non-volatile, and toxic Small, easy to store, easy to use, has important academic and application value.
- the invention provides a preparation method of the fluorosulfonyl radical reagent, which is simple to operate and suitable for large-scale production.
- Fig. 1 is the 1 H NMR figure of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;
- Fig. 2 is the 19 F NMR chart of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;
- Fig. 3 is the 13 C NMR chart of 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-imidazole trifluoromethanesulfonate prepared in Example 2;
- Figure 4 is the 1 H NMR figure of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 ;
- Figure 5 is the 19 F NMR chart of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 ;
- Figure 6 is the 13 C NMR figure of 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate prepared in Example 3 .
- the present invention provides a fluorosulfonyl radical reagent, including a cation and an anion, and the cation has a structure shown in formula I-1 or formula I-2:
- R 1 and R 2 are independently hydrogen or an alkyl group
- R 3 is an alkyl group
- Ar 1 and Ar 2 are independently an aromatic ring or a substituted aromatic ring;
- the anion is - BF 4 , - BF 6 , - PF 6 , - PF 4 , - SbF 6 , - NTf 2 or - AsF 6 .
- the aromatic ring is preferably a benzene ring, a naphthalene ring, an anthracene ring or a phenanthrene ring
- the substituent in the substituted aromatic ring is preferably an alkyl group or an electron-deficient group.
- the electron deficient group preferably includes -F, -Cl, -Br, trifluoromethyl, nitrile, nitro, ester, aldehyde, acetyl, fluorosulfonyl, benzenesulfonyl or Alkylsulfonyl.
- the alkyl group can be a straight-chain alkyl group, or a branched-chain alkyl group or a cycloalkyl group; in the present invention, the number of carbon atoms in the alkyl group is preferably 1 to 8, more preferably 1 to 3, specifically methyl.
- the cation of the fluorosulfonyl radical reagent is specifically any one of the compounds shown in formula 1 to formula 9:
- R 1 and R 2 are independently hydrogen or alkyl
- R 3 is alkyl
- R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 and R 32 are independently hydrogen, alkyl or electron deficient group.
- the optional ranges of the alkyl group and the electron-deficient group are the same as those in the above technical solution, and will not be repeated here.
- the fluorosulfonyl free radical reagent can specifically be
- the present invention provides a preparation method of the fluorosulfonyl radical reagent described in the above technical solution.
- the present invention is based on the targeted selection of the anion species in the fluorosulfonyl free radical reagent.
- the preparation method is specifically described below.
- the preparation method of described fluorosulfonyl radical reagent comprises the following steps:
- the first raw material has a structure shown in formula II-1 or formula II-2
- the first intermediate product has a structure shown in formula III-1 or formula III-2:
- the second raw material is R 3 OTf, R 3 OSO 2 F or R 3 HSO 4 .
- the alkaline reagent preferably includes an inorganic alkaline reagent or an organic alkaline reagent
- the inorganic base preferably includes sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate , potassium phosphate, potassium tert-butoxide, sodium methoxide, sodium ethoxide and sodium hydride, more preferably sodium hydride
- the organic base preferably includes triethylamine, N,N-diisopropylethyl One or more of amine, pyrrole and pyridine, more preferably triethylamine.
- the organic solvent preferably includes acetonitrile, dichloromethane, ethyl acetate, benzene, toluene, acetone, 1,4-dioxane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, di One or more of methyl sulfoxide, N,N-dimethylformamide, N-methylpyrrolidone, methyl tert-butyl ether and chloroform, more preferably acetonitrile or N,N-dimethylformamide amides.
- the molar ratio of the first raw material, sulfuryl fluoride and alkaline reagent is preferably 6:(7-7.5):(7-16), more preferably 6:7.3:(7.2-15);
- the amount of the organic solvent used is not particularly limited, as long as the nucleophilic substitution reaction proceeds smoothly.
- the first raw material, sulfuryl fluoride, basic reagent and organic solvent are mixed, preferably the first raw material, basic reagent and organic solvent are mixed, and then passed through the mixed system under negative pressure.
- Sulfuryl fluoride gas is introduced; in the embodiment of the present invention, specifically, the mixed system is pumped to a negative pressure by a water pump, and then sulfuryl fluoride gas is introduced with a balloon.
- the temperature of the nucleophilic substitution reaction is preferably -50 to 100°C, more preferably 20 to 50°C.
- the nucleophilic substitution reaction can be carried out at room temperature, that is, no additional heating or Cooling; in the embodiment of the present invention, the room temperature is specifically 25°C.
- the time for the nucleophilic substitution reaction is preferably 1-48 hours, more preferably 5-30 hours, and even more preferably 10-12 hours.
- the nucleophilic substitution reaction is preferably carried out under stirring conditions. The present invention has no special limitation on the stirring conditions, and the stirring rate well known to those skilled in the art can be used.
- the first raw material, the basic reagent and the organic solvent are mixed, and the mixed system is pumped to negative pressure.
- the present invention preferably monitors the reaction process by TLC; after the reaction is completed, the present invention preferably quenches the resulting reaction solution with saturated ammonium chloride solution, extracts with dichloromethane, and washes with saturated brine after the organic phases are combined, and then passes through anhydrous sulfuric acid sodium drying, filtering, and the filtrate was concentrated to dryness by rotary evaporation, and the obtained residue was a crude product containing the first intermediate product, which was directly followed by the first electrophilic reaction; or the filtrate was concentrated to dryness by rotary evaporation, and the obtained
- the residue is separated by column chromatography to obtain the first intermediate product; the reagents used in the column chromatography separation are petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably 20:1.
- the present invention mixes the first intermediate product, the second raw material and an organic solvent to perform a first electrophilic reaction to obtain a fluorosulfonyl free radical reagent.
- the organic solvent preferably includes acetonitrile, dichloromethane, diethyl ether, tetrahydrofuran, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, methyl tert-butyl One or more of base ether and chloroform, more preferably dichloromethane.
- the molar ratio of the first intermediate product to the second raw material is preferably 1: (1.1-2.0), and the present invention has no special limitation on the amount of the organic solvent, so as to ensure the smooth progress of the first electrophilic reaction. Can.
- the first intermediate product and the second raw material are mixed with an organic solvent, specifically in a protective atmosphere, the first intermediate product is mixed with an organic solvent (or the mixed material liquid containing the first intermediate product is mixed with an organic solvent) solvent mixing), under ice bath (0°C) and stirring conditions, dropwise add the second raw material to the obtained mixed system; in the embodiment of the present invention, specifically, use a syringe to add the second raw material dropwise to the mixed system , the rate of the dropwise addition is preferably 4-5 mL/min, more preferably 4.5 mL/min.
- the temperature of the first electrophilic reaction is preferably -50 to 100°C, more preferably -20 to 50°C.
- the first electrophilic reaction can be carried out at room temperature; specifically, the second raw material drop After the addition, the ice in the ice bath melted naturally and returned to room temperature for the first electrophilic reaction.
- the time for the first electrophilic reaction is preferably 1-48 hours, more preferably 3-20 hours, and even more preferably 6-8 hours.
- the present invention preferably monitors the first electrophilic reaction process by LC-MS; after the reaction is completed, the present invention preferably concentrates the obtained reaction solution through rotary evaporation, adds methyl tert-butyl ether to the obtained residue, stirs to separate out solids, and The supernatant was poured out, and the obtained solid was washed with methyl tert-butyl ether, and the target product fluorosulfonyl radical reagent was obtained after removing the solvent; remove.
- the preparation method of the fluorosulfonyl radical reagent include the following steps:
- the third raw material is AgBF 4 , AgBF 6 , AgPF 6 , AgPF 4 , AgSbF 6 , AgNTf 2 or AgAsF 6 .
- the first intermediate product is the first intermediate product described in the above technical solution, which will not be repeated here.
- the invention mixes the first intermediate product, methyl iodide and an organic solvent to carry out the second electrophilic reaction to obtain the second intermediate product.
- the molar ratio of the first intermediate product to methyl iodide is preferably 1:(1.05-5.0), more preferably 1:(2.5-3.5).
- the organic solvent preferably includes tetrahydrofuran or acetonitrile.
- there is no special limitation on the amount of the organic solvent as long as the second electrophilic reaction can proceed smoothly.
- the method of mixing the first intermediate product, methyl iodide and organic solvent is not particularly limited in the present invention, as long as each component can be mixed evenly.
- the temperature of the second electrophilic reaction is preferably -50 to 200°C, more preferably 0 to 100°C, further preferably 20 to 50°C; the time is preferably 1 to 48h, more preferably 12 to 24h, more preferably 15-20h.
- the present invention preferably concentrates the obtained product system through rotary evaporation, and then drains the solvent through an oil pump to obtain the second intermediate product.
- the present invention mixes the second intermediate product, the third raw material and an organic solvent to perform anion exchange reaction to obtain a fluorosulfonyl free radical reagent.
- the molar ratio of the second intermediate product to the third raw material is preferably 1:(1.05-5.0), more preferably 1:(2.5-3.5).
- the organic solvent preferably includes tetrahydrofuran or acetonitrile.
- there is no special limitation on the amount of the organic solvent as long as the second electrophilic reaction can proceed smoothly.
- the method of mixing the second intermediate product, the third raw material and the organic solvent is not particularly limited in the present invention, as long as each component can be mixed evenly.
- the temperature of the anion exchange reaction is preferably -50 to 100°C, more preferably -30 to 80°C, further preferably -5 to 30°C; the time is preferably 1 to 48 hours, more preferably 4 to 12h, more preferably 6-10h.
- the present invention preferably concentrates the obtained product system by rotary evaporation, adds diethyl ether to the obtained residue, stirs to precipitate a solid, pours out the supernatant, washes the obtained solid with diethyl ether, and removes the solvent to obtain the target
- the product is a fluorosulfonyl free radical reagent; in the embodiments of the present invention, an oil pump is used to drain the solvent, so as to realize the removal of the solvent.
- the present invention provides the application of the fluorosulfonyl radical reagent described in the above technical scheme in the fluorosulfonyl radical reaction.
- the application preferably includes the following steps:
- reaction substrate fluorosulfonyl radical reagent, photosensitizer and organic solvent are mixed, and the fluorosulfonyl radical reaction is carried out under the irradiation conditions of ultraviolet light, blue light or visible light to obtain a fluorosulfonylated product;
- the reaction substrate includes alkenes or alkynes.
- the olefin compound preferably has formula IV-1, formula IV-2, formula IV-3, formula IV-4, formula IV-5, formula IV-6, formula IV-7, formula IV-8 Or the structure shown in formula IV-9:
- R preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl
- the substituents preferably independently include alkyl groups, electron-rich groups or electron-poor groups, and the electron-rich groups are preferably methoxy, ethoxy, propoxy, butoxy, dimethylamino, diethyl Amino group, methylthio group or ethylthio group, the optional range of the alkyl group and the electron-deficient group is preferably consistent with the above-mentioned technical solution, and will not be repeated here;
- R2 preferably includes phenyl, substituted phenyl, ester group or carbonyl
- R3 preferably includes hydrogen, phenyl or substituted phenyl
- R4 preferably includes hydrogen, alkyl, phenyl or substituted Phenyl
- the substituent in the substituted phenyl group preferably includes an alkyl group, an electron-rich group or an electron-deficient group, and the optional range of the alkyl group, an electron-rich group and an electron-deficient group is preferably the same as the above-mentioned technical scheme are consistent, and will not be repeated here;
- R preferably includes hydrogen or alkyl
- Ar preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, the substituted phenyl, substituted
- the substituents in naphthyl and substituted biphenyl preferably independently include alkyl groups, electron-rich groups or electron-deficient groups, and the optional ranges of the alkyl groups, electron-rich groups and electron-deficient groups are preferably the same as those of the above-mentioned technology The scheme is consistent and will not be repeated here;
- R 6 preferably includes hydrogen, alkyl, phenyl or acyl, and n is preferably 1 or 2;
- X is preferably O or S
- R7 preferably includes hydrogen, alkyl, phenyl or acyl
- the optional range of the alkyl group is preferably consistent with the above-mentioned technical scheme, and specifically can be a straight chain Alkyl or cycloalkyl, preferably cyclohexane;
- R 8 and R 9 preferably independently include alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl, substituted biphenyl or acyl, and the substituted phenyl
- the substituents in , substituted naphthyl and substituted biphenyl preferably independently include an alkyl group, an electron-rich group or an electron-deficient group, and the optional ranges of the alkyl group, the electron-rich group and the electron-deficient group are preferably the same as Consistent in the above-mentioned technical scheme, no longer repeat them here;
- m is preferably 1-4;
- Ar preferably includes phenyl, naphthyl, biphenyl, substituted phenyl, substituted naphthyl or substituted biphenyl, and in the substituted phenyl, substituted naphthyl and substituted biphenyl
- the substituent preferably independently includes an alkyl group, an electron-rich group or an electron-deficient group, and the optional range of the alkyl group, an electron-rich group and an electron-deficient group is preferably consistent with the above-mentioned technical solution, and will not be repeated here. ;
- R 10 , R 11 , R 12 and R 13 preferably independently include hydrogen, alkyl, phenyl, naphthyl, biphenyl, substituted phenyl, substituted Naphthyl or substituted biphenyl
- the substituents in the substituted phenyl, substituted naphthyl and substituted biphenyl preferably independently include alkyl, electron-rich groups or electron-poor groups, the alkyl, electron-rich
- the optional ranges of groups and electron-deficient groups are preferably consistent with those in the above-mentioned technical solution, and will not be repeated here.
- the molar ratio of the reaction substrate to the fluorosulfonyl radical reagent is preferably 0.1:(0.15-0.4), more preferably 1:(0.2-0.3).
- the photosensitizer preferably includes a metal complex photocatalyst or an organic photocatalyst; the metal complex photocatalyst preferably includes an Ir complex, a Ru complex or a Cu complex, and the Ir complex is preferably Ir (ppy) 3 ; the organic photocatalyst preferably includes PTH, EosinY or 4CzIPN.
- the molar ratio of the reaction substrate to the photosensitizer is preferably 0.1:(0.001-0.01).
- the organic solvent preferably includes 1,4-dioxane, tetrahydrofuran or diethyl ether; in the present invention, there is no special limitation on the amount of the organic solvent, as long as the fluorosulfonyl radical reaction proceeds smoothly.
- the fluorosulfonyl radical reaction can be carried out in the presence or absence of an inorganic alkali reagent.
- the fluorosulfonyl radical reaction is preferably carried out in the presence of an inorganic alkali Carry out under reagent existence condition, described inorganic base reagent preferably comprises one or more in potassium carbonate, sodium carbonate, potassium phosphate and sodium bicarbonate;
- the mol ratio of described reaction substrate and inorganic base reagent is preferably 0.1:( 0.1 ⁇ 0.3);
- the effect of described inorganic alkaline reagent is to neutralize the acid produced in the reaction.
- the temperature of the fluorosulfonyl radical reaction is preferably -60 to 100°C, more preferably 15 to 40°C.
- the fluorosulfonyl radical reaction can be carried out at room temperature; the fluorine
- the time for the sulfonyl radical reaction is preferably 1-72 h, more preferably 6-18 h.
- the fluorosulfonyl radical reaction is preferably carried out under a protective atmosphere and stirring conditions, and the protective gas providing the protective atmosphere is preferably argon, and the present invention has no special limitation on the rate of stirring. Stirring rates known to those skilled in the art will suffice.
- the present invention has no special limitation on the light source that provides ultraviolet light, blue light or visible light, and the light source well known to those skilled in the art can be used; in the embodiment of the present invention, specifically, the fluorosulfonyl radical In response, the light source that provides blue light is preferably a blue LED light.
- the present invention preferably removes the solvent in the resulting reaction solution, and separates the obtained crude product by silica gel column chromatography to obtain the fluorosulfonylated product.
- the solvent in the reaction solution is removed
- the method is preferably vacuum distillation.
- the developing agent used in the silica gel column chromatography separation is preferably petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether and ethyl acetate is preferably 40:1; the silica gel column chromatography separation adopts The silica gel particle size is preferably 200-300 mesh.
- the 2-phenyl-1H-benzimidazole-1-sulfonyl fluoride was mixed with dichloromethane (600mL), cooled to 0°C in an ice bath, and 4.5mL Methyl trifluoromethanesulfonate (592mmol) was added dropwise at a rate of 1/min, the ice in the ice bath melted naturally and returned to room temperature, reacted at room temperature for 4h, and LC-MS monitored the completion of the reaction; the reaction solution was concentrated by a rotary evaporator To dryness, add methyl tert-butyl ether (500mL) to the resulting residue, stir to precipitate a solid, pour off the supernatant, and wash the obtained solid with methyl tert-butyl ether (500mL ⁇ 2), then use an oil pump to pump The solvent was dried, and the obtained white solid was 1-(fluorosulfonyl)-3-methyl-2-phenyl-1H-
- Example 15 Prepare 1-(fluorosulfonyl)-3-methyl-2-(4-trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate according to the method of Example 15, except that In Example 15, "2-phenylbenzimidazole” was replaced with "2-(4-trifluoromethylphenyl)benzimidazole”; the final white solid obtained was 1-(fluorosulfonyl)-3-methyl -2-(4-Trifluoromethylphenyl)-1H-benzimidazole trifluoromethanesulfonate, the total yield was 82%.
- the fluorosulfonyl radical reagents used in Comparative Examples 1 to 3 are Compound 2b, Compound 2c and Compound 2e respectively, and the specific structures and involved reaction formulas are as follows:
- the structure and yield of the sulfonylated product are shown in Table 2, and the general reaction formula is as follows:
- a in Table 2 indicates that the amount of fluorosulfonyl radical reagent used in the preparation process is 0.2 mmol, and b indicates that the amount of fluorosulfonyl free radical reagent used in the preparation process is 0.3 mmol.
- the structure and yield of the sulfonylated product (corresponding to 3ba) are shown in Table 3, and the general reaction formula is as follows:
- the difference is that the substrate in application example 1 is replaced by
- the amount of fluorosulfonyl radical reagent used in the preparation process was 0.3 mmol.
- the structure of the substrate, the structure of the fluorosulfonylated products (corresponding to 3bb and 3bc) and the yield are shown in Table 3.
- the general reaction formula is as follows:
- the structure, fluorosulfonylation product structure (corresponding to 3bd ⁇ 3bs) and yield are shown in Table 3.
- the general reaction formula is as follows:
- the yield in brackets is the yield data when 0.3mmol of FSO 2 Cl is used to prepare fluorosulfonylated products
- the yield outside the brackets is the yield of fluorosulfonylation provided by the present invention using 0.3mmol Yield data for the preparation of fluorosulfonylated products by acyl radical reagents.
- the difference is that the substrate in application example 1 is replaced by And add 0.1mmol K 2 CO 3 ; the substrate structure, fluorosulfonylation product (corresponding to 3ca and 3cb) structure and yield are shown in Table 4, and the general reaction formula is as follows:
- the difference is that the substrate in application example 1 is replaced by And add 0.1mmol K 2 CO 3 ; the structure of the substrate, the structure of the fluorosulfonylated product (corresponding to 3cc) and the yield are shown in Table 4.
- the general reaction formula is as follows:
- the difference is that the substrate in application example 1 is replaced by And add 0.1mmol K 2 CO 3 ; the structure of the substrate, the structure of the fluorosulfonylation product (corresponding to 3cd) and the yield are shown in Table 4.
- the general reaction formula is as follows:
- the fluorosulfonyl free radical reagent provided by the present invention is applicable to a wide range of substrates, including substituted or unsubstituted phenyl olefins, naphthyl olefins, biphenyl olefins, cyclic phenyl olefins, disubstituted, Trisubstituted phenylalkenes (in particular, triphenylethylene also yields high yields), electron-deficient phenylalkenes, and various alkenyl ethers, alkenyl amines, and thioether alkenes substrates .
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Abstract
La présente invention concerne un réactif de radicaux libres fluorosulfonyle et un procédé de préparation associé et son utilisation, appartenant au domaine technique de la synthèse organique. Le réactif de radicaux libres fluorosulfonyle de la présente invention peut efficacement générer des radicaux libres fluorosulfonyle et conduit à une réaction radicalaire correspondante, et le rendement en le produit est élevé. De plus, le réactif de radicaux libres fluorosulfonyle de la présente invention peut s'appliquer à une gamme extrêmement large de substrats et peut être mis à réagir avec différents types de substrats oléfiniques et de substrats de type alcyne, dans le but de synthétiser efficacement des produits de fluorosulfonylation. En outre, le réactif de radicaux libres fluorosulfonyle de la présente invention se trouve dans un état solide stable à la température ambiante, il n'est pas volatil, sa toxicité est faible, il est facile à stocker et commode à utiliser, et présente une valeur élevée, au niveau universitaire et pour les applications. En outre, la présente invention porte sur un procédé de préparation du réactif de radicaux libres fluorosulfonyle. Le procédé de préparation est facile à exploiter et convient à une production à grande échelle.
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