CN115785052A - Method for synthesizing isocoumarin with high selectivity under catalysis of polyacid - Google Patents
Method for synthesizing isocoumarin with high selectivity under catalysis of polyacid Download PDFInfo
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- CN115785052A CN115785052A CN202211458197.4A CN202211458197A CN115785052A CN 115785052 A CN115785052 A CN 115785052A CN 202211458197 A CN202211458197 A CN 202211458197A CN 115785052 A CN115785052 A CN 115785052A
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- polyacid
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- high selectivity
- isocoumarin
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- IQZZFVDIZRWADY-UHFFFAOYSA-N isocoumarin Chemical compound C1=CC=C2C(=O)OC=CC2=C1 IQZZFVDIZRWADY-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 73
- 239000003054 catalyst Substances 0.000 claims abstract description 36
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 8
- 239000011630 iodine Substances 0.000 claims abstract description 8
- 230000001681 protective effect Effects 0.000 claims abstract description 5
- 239000011734 sodium Substances 0.000 claims description 24
- 239000007789 gas Substances 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 239000003446 ligand Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 8
- 229930182821 L-proline Natural products 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 229960002429 proline Drugs 0.000 claims description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 4
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- VKWJMTLAAJULGF-UHFFFAOYSA-N methoxymethyl formate Chemical compound COCOC=O VKWJMTLAAJULGF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 12
- 230000008878 coupling Effects 0.000 abstract description 11
- 238000010168 coupling process Methods 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000006617 Intramolecular Heck reaction Methods 0.000 abstract description 4
- 238000007337 electrophilic addition reaction Methods 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000007086 side reaction Methods 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 20
- 239000001301 oxygen Substances 0.000 description 20
- 229910052760 oxygen Inorganic materials 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- 239000012467 final product Substances 0.000 description 18
- 239000010453 quartz Substances 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 238000000926 separation method Methods 0.000 description 16
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 10
- -1 lactone compounds Chemical class 0.000 description 9
- 238000005286 illumination Methods 0.000 description 7
- 150000002512 isocoumarins Chemical class 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 6
- 230000001699 photocatalysis Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 4
- 238000007341 Heck reaction Methods 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 150000001345 alkine derivatives Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 2
- RIUPLDUFZCXCHM-UHFFFAOYSA-N Urolithin A Chemical compound OC1=CC=C2C3=CC=C(O)C=C3OC(=O)C2=C1 RIUPLDUFZCXCHM-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- TZDXNFAAJNEYIO-UHFFFAOYSA-N 1-bromo-3-ethynylbenzene Chemical group BrC1=CC=CC(C#C)=C1 TZDXNFAAJNEYIO-UHFFFAOYSA-N 0.000 description 1
- ZVWWYEHVIRMJIE-UHFFFAOYSA-N 1-butyl-4-ethynylbenzene Chemical group CCCCC1=CC=C(C#C)C=C1 ZVWWYEHVIRMJIE-UHFFFAOYSA-N 0.000 description 1
- GRBJPHPMYOUMJV-UHFFFAOYSA-N 1-chloro-3-ethynylbenzene Chemical group ClC1=CC=CC(C#C)=C1 GRBJPHPMYOUMJV-UHFFFAOYSA-N 0.000 description 1
- YFPQIXUNBPQKQR-UHFFFAOYSA-N 1-ethynyl-2-fluorobenzene Chemical group FC1=CC=CC=C1C#C YFPQIXUNBPQKQR-UHFFFAOYSA-N 0.000 description 1
- PTRUTZFCVFUTMW-UHFFFAOYSA-N 1-ethynyl-3-fluorobenzene Chemical group FC1=CC=CC(C#C)=C1 PTRUTZFCVFUTMW-UHFFFAOYSA-N 0.000 description 1
- RENYIDZOAFFNHC-UHFFFAOYSA-N 1-ethynyl-3-methylbenzene Chemical group CC1=CC=CC(C#C)=C1 RENYIDZOAFFNHC-UHFFFAOYSA-N 0.000 description 1
- QXSWHQGIEKUBAS-UHFFFAOYSA-N 1-ethynyl-4-fluorobenzene Chemical group FC1=CC=C(C#C)C=C1 QXSWHQGIEKUBAS-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- ZSYQVVKVKBVHIL-UHFFFAOYSA-N 1-tert-butyl-4-ethynylbenzene Chemical group CC(C)(C)C1=CC=C(C#C)C=C1 ZSYQVVKVKBVHIL-UHFFFAOYSA-N 0.000 description 1
- NSKPFWAAYDFCFS-UHFFFAOYSA-N 2,5-diiodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC=C1I NSKPFWAAYDFCFS-UHFFFAOYSA-N 0.000 description 1
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- LRRDANNSUCQNDU-UHFFFAOYSA-N 4-chloro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1I LRRDANNSUCQNDU-UHFFFAOYSA-N 0.000 description 1
- DUKFTVLJAXWGPI-UHFFFAOYSA-N 4-fluoro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1I DUKFTVLJAXWGPI-UHFFFAOYSA-N 0.000 description 1
- IGBNDUKRHPTOBP-UHFFFAOYSA-N 5-bromo-2-iodobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1I IGBNDUKRHPTOBP-UHFFFAOYSA-N 0.000 description 1
- NRPQWTVTBCRPEL-UHFFFAOYSA-N 5-chloro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1I NRPQWTVTBCRPEL-UHFFFAOYSA-N 0.000 description 1
- XPFMQYOPTHMSJJ-UHFFFAOYSA-N 5-fluoro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1I XPFMQYOPTHMSJJ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- RZTOWFMDBDPERY-UHFFFAOYSA-N Delta-Hexanolactone Chemical group CC1CCCC(=O)O1 RZTOWFMDBDPERY-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- JPGRSTBIEYGVNO-UHFFFAOYSA-N methyl 4-ethynylbenzoate Chemical compound COC(=O)C1=CC=C(C#C)C=C1 JPGRSTBIEYGVNO-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- 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 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 238000007539 photo-oxidation reaction Methods 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000005506 phthalide group Chemical group 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
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- 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
- Y02P20/584—Recycling of catalysts
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention belongs to the technical field of compound synthesis, and particularly relates to a method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid. The method comprises the following steps: at room temperature, the compound shown in the formula I and the compound shown in the formula II are used as raw materials, under the alkaline environment, an iodine source and protective gas, ultraviolet light is used for assisting the catalysis of a polyacid catalyst, electrophilic addition reaction is firstly carried out, then intramolecular Heck coupling is carried out, and the isocoumarin is synthesized in a high-selectivity mode. The invention solves the problem that 2-alkynylbenzoic acid generated by Sonogashira type coupling is used as an intermediate and has low regioselectivity when an inner ring is closed. The invention firstly carries out electrophilic addition and then carries out intramolecular Heck coupling, regulates and controls the regioselectivity of the reaction, greatly reduces the occurrence of side reactions, has simple reaction system, mild conditions and good compatibility to functional groups.
Description
Technical Field
The invention belongs to the technical field of compound preparation, and particularly relates to a novel method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid.
Background
Isocoumarin compounds are natural lactone compounds widely existing in nature, and have physiological and biological activities (such as Urolithin A) of resisting bacteria, diminishing inflammation, inhibiting protease, weeding, resisting cancer and the like, and the basic parent nucleus of the isocoumarin compounds is benzo hexa-lactone ring. Because the isocoumarin compound has anticancer activity, the synthetic method is always a hot spot in organic synthesis.
In the existing studies, the traditional transition metal catalyzed 5-exo-dig or 6-endo-dig cyclization of 2-alkynylbenzoic acids obtained by Sonogashira type coupling or generated in situ is one of the most attractive methods for the synthesis of phthalates and isocoumarins as shown in the following equation:
depending on the cyclization route, phthalides can be generated by 5-exo-dig cyclization or isocoumarin can be generated by 6-endo-dig cyclization. As in 2009, jean-Luc Parrain reported a copper (I) catalyzed cross-coupling synthesis of terminal alkynes with ortho-iodo unsaturated acid derivatives (adv.synth.cat., 2009,351, 779-788.); in 2011, so Won Youn reports a method for obtaining phthalide and isocoumarin compounds by regioselective and stereoselective oxidative cyclization reaction of o-alkynylbenzaldehyde under the catalysis of NHC (org. Lett.,2011,13,2228-2231.). Although these methods have a high substrate range, their regioselectivity is generally low, and control over regioselectivity is lacking.
In 2013, kumar task group reports a method for selectively synthesizing isocoumarin compounds by using copper to catalyze the coupling of 2-iodobenzoic acid and terminal alkyne and carefully regulating and controlling reaction temperature (adv. Synth. Catal.2013,355, 3221-3230), heat is released in the reaction process, and the reaction temperature is accurately regulated and controlled, so that the method is difficult; chaudhary studied the method of synthesizing isocoumarin derivatives from 2-bromobenzoic acid and terminal alkyne through coupling cyclization in 2018 by using nano-scale silver oxide as a catalyst, and the synthesis of isocoumarin was realized by regulating and controlling steric hindrance of substituents in the reaction, and the substrate universality was poor (RSC adv.,2018,8,23152).
In summary, the most attractive route for the synthesis of isocoumarin derivatives is the Sonogashira coupling catalyzed by the traditional transition metals Pd or Cu. However, the 2-alkynylbenzoic acid intermediate produced by Sonogashira-type coupling has a problem of low regioselectivity when the inner ring is closed. The reported few regioselective methods often require careful regulation of steric hindrance, acid and alkali control, or temperature control, and are harsh in conditions. Therefore, it is necessary to develop a new method with mild reaction conditions, environmental protection and high chemical selectivity.
Heck-type reactions are traditionally catalyzed by palladium and undergo a Pd event 0 /pd II And (4) catalytic circulation. Solar energy is used as clean energy and is relatively less applied to organic reaction; the high-efficiency conversion from solar energy to chemical energy is realized through the photocatalytic coupling reaction. Currently, photocatalytic Heck reaction reports are very few; in 2020, zolt n Nov k reports a method of visible light-induced palladium-catalyzed fluoroalkylation (org. Lett.2020,22, 8091-8095); in the same year, frank glorious reported a palladium-catalyzed three-component approach to disrupting the free radical Heck/allyl substitution cascade, which also required BINAP phosphine ligand assistance (j.am.chem.soc.2020,142, 10173-10183). Palladium catalysts have good performance, but palladium catalysts are toxic and expensiveExpensive; meanwhile, the homogeneous palladium catalyst is easy to cause metal pollution and residue problems, and the homogeneous palladium catalytic method is difficult to be applied in actual production. In addition, the alkyl halides are the predominant halogenated hydrocarbons in the photocatalytic Heck reaction reported previously, while relatively few reports have been made on the photocatalytic Heck coupling of aryl halides.
Polyoxometalates (POMs) are structurally diverse anion clusters formed by the attachment of early transition metal ions through oxygen. Has the following characteristics:
(1) Adjustable chemical components (different rare earth elements are loaded, the band gap is adjusted, and the photo-oxidation reduction capability is further adjusted);
(2) A unique electronic structure;
(3) A nucleophilic oxygen-rich surface;
(4) Reversible electronic redox activity.
At present, the application of polyacid in organic synthesis under light induction is relatively less, and the photocatalytic Heck reaction based on halogenated aromatic hydrocarbon is not reported.
Disclosure of Invention
The invention aims to solve the problem that the regioselectivity is low or the conditions of a regioselectivity method are harsh when isocoumarin is prepared in the prior art, and provides a novel method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention relates to a novel method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid, which comprises the following steps:
under the conditions of room temperature, alkaline environment, iodine source and protective gas, in a solvent, an ultraviolet light-assisted polyacid catalyst is used for catalyzing a compound shown in a formula I and a compound shown in a formula II to react, electrophilic addition reaction is firstly carried out on raw materials at room temperature, then intramolecular Heck coupling is carried out, and isocoumarin shown in a formula III is synthesized in a high-selectivity mode. The synthetic route is as follows:
wherein: r 1 Selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, and R 1 The substituent is positioned at the ortho-position, meta-position or para-position of the carboxyl; r 2 Selected from hydrogen, fluorine, chlorine, bromine, methyl, methoxy, methyl formate, n-butyl, tert-butyl, phenyl, and R 2 The substituents are located at the ortho, meta or para positions. The polyacid catalyst is a photosensitive catalyst which can absorb under the light of ultraviolet light.
The molar ratio of the compound shown as the formula I to the compound shown as the formula II is 1:3.
Adding an alkali in the reaction, wherein the alkali is any one of cesium carbonate, tripotassium phosphate, potassium carbonate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide and triethylamine; the molar ratio of the base to the compound shown in the formula I is 3:1; the base is intended to provide an alkaline environment for the reaction.
The reaction is also added with a ligand, wherein the ligand is any one of L-proline, 1,10-phenanthroline, 2,2-bipyridine and triphenylphosphine. The addition amount of the ligand is 20mol% of the compound shown in the formula I; the ligand has the function of adjusting acid-base balance and keeping the reaction under the alkaline condition all the time.
The iodine source is KI, naI or I 2 The amount of the iodine source added is 1 equivalent of that of the compound shown in the formula I, and the iodine source is used for providing electrons.
The solvent may be selected from one of dimethyl sulfoxide (DMSO), acetonitrile, toluene, tetrahydrofuran (THF), and N, N-Dimethylformamide (DMF). In the reaction, the solvent is used to dissolve the compound of formula I. The ratio of the added solvent to the compound shown in the formula I is as follows: solvent =3mmol of compound of formula I.
The ultraviolet light is 200-400 nm ultraviolet light. The polyacid catalyst is a photosensitive catalyst which can absorb under the light of ultraviolet light of 200-400 nm. When the used photosensitive catalyst has absorption under the illumination of 200-400 nm, the reaction can be promoted.
The polyacid catalyst can be selected from H 3 [PMo 12 O 40 ]、Na 10 [α-SiW 9 O 34 ]·18H 2 O、H 6 [P 2 W 18 O 62 ]、Na 12 [α-P 2 W 15 O 56 ]·24H 2 O、[H 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O、[H 2 N-CH 3 ) 2 ] 6 Na 4 [Ce 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 And O is one of the compounds. The addition amount of the polyacid catalyst is 1-10 mol% of the compound shown in the formula I.
The protective gas is nitrogen.
Compared with the prior art, the invention has the beneficial effects that:
the method can be carried out at room temperature, and compared with the Sonogashira coupling carried out under the catalysis of the traditional transition metal Pd/C or Cu, the polyacid has good thermal stability, is a very excellent photocatalyst, can be repeatedly utilized, and has no loss of activity; on the mechanism, the invention solves the problem that 2-alkynylbenzoic acid generated by Sonogashira type coupling is used as an intermediate, and the regioselectivity is low when the inner ring is closed. The invention firstly carries out electrophilic addition and then carries out intramolecular Heck coupling, regulates and controls the regional selectivity of the reaction, greatly reduces the occurrence of side reaction, has simple reaction system, mild condition and good compatibility to functional groups.
Drawings
FIG. 1 is a NMR spectrum of 3-phenyl-1H-isochroman-1-one in example I.
FIG. 2 is a carbon nuclear magnetic resonance spectrum of 3-phenyl-1H-isochroman-1-one from example I.
FIG. 3 is a NMR spectrum of 6-chloro-3- (m-tolyl) -1H-isochroman-1-one in example VII.
FIG. 4 is a carbon nuclear magnetic resonance spectrum of 6-chloro-3- (m-tolyl) -1H-isochroman-1-one in example VII.
FIG. 5 is a NMR spectrum of 3- (4-methoxyphenyl) -1H-isochroman-1-one in example VIII.
FIG. 6 is a carbon nuclear magnetic resonance spectrum of 3- (4-methoxyphenyl) -1H-isochroman-1-one in example VIII.
FIG. 7 is a NMR spectrum of 3- (4-tert-butylphenyl) -1H-isochroman-1-one in example eleven.
FIG. 8 is a NMR carbon spectrum of 3- (4-tert-butylphenyl) -1H-isochroman-1-one in the eleventh embodiment.
Detailed Description
The present invention will be described in more detail with reference to the following embodiments for understanding the technical solutions of the present invention, but the present invention is not limited to the scope of the present invention.
EXAMPLE one preparation of 3-phenyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 1mmol% of polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of cesium carbonate, 1 equivalent of KI, 20mmol% of L-proline, then 2mL of DMSO is added, and finally 0.9mmol of phenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 3-phenyl-1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 80%. The reaction equation is as follows:
EXAMPLE preparation of bis 3- (2-fluorophenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and adding 0.3mmol of 2-iodobenzeneFormic acid, 3mmol% polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of tripotassium phosphate, 1 equivalent of NaI, 20mmol percent of 1,10-phenanthroline, then adding 2mL of acetonitrile, and finally adding 0.9mmol of 2-fluorophenylacetylene. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under illumination with 310nm UV light and monitored by TLC. Finally, the final product 3- (2-fluorophenyl) -1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 67 percent, and the reaction equation is as follows:
EXAMPLE preparation of tris 3- (3-fluorophenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 5mmol% of polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of potassium carbonate, 1 equivalent of I 2 20mmol% 2,2-bipyridine, then 2mL toluene was added, and finally 0.9mmol 3-fluorophenylacetylene was added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under 365nm UV light and monitored by TLC. Finally, the final product 3- (3-fluorophenyl) -1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 70 percent, and the reaction equation is as follows:
EXAMPLE preparation of tetrakis 3- (4-fluorophenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 7mmol% of polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of lithium tert-butoxide, 1 equivalent of I 2 20mmol% triphenylphosphine, then 2mL tetrahydrofuran, and finally 0.9mmol 4-fluorophenylacetylene. Then, the mixture is fed to a reactorThe replacement of the qi body ensures that no water and no oxygen exist. The reaction was carried out for 36h under 365nm UV light illumination and monitored by TLC. Finally, the final product 3- (4-fluorophenyl) -1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 75 percent, and the reaction equation is as follows:
EXAMPLE preparation of penta 7-chloro-3- (3-chlorophenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 5-chloro-2-iodobenzoic acid and 9mmol% of polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of sodium tert-butoxide, 1 equivalent of KI and 20mmol percent of triphenylphosphine, then 2mL of N, N-dimethylformamide is added, and finally 0.9mmol of 3-chlorophenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 7-chloro-3- (3-chlorphenyl) -1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 62 percent, and the reaction equation is as follows:
EXAMPLE preparation of hexa-3- (3-bromophenyl) -7-methyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodine-5-methylbenzoic acid and 10mmol% of polyacid catalyst Na 10 [α-SiW 9 O 34 ]·18H 2 O, 0.9mmol of potassium tert-butoxide, 1 equivalent of KI, 20mmol% of L-proline, then 2mL of DMSO is added, and finally 0.9mmol of 3-bromophenylacetylene is added. Then gas replacement is carried out to ensure that no water and no oxygen exist. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 3- (3-bromophenyl) -7-methyl-1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 58 percent of the reaction formulaThe formula is as follows:
EXAMPLE preparation of hepta 6-chloro-3- (m-tolyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 4-chloro-2-iodobenzoic acid and 10mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of triethylamine, 1 equivalent of NaI, 20mmol% of 1,10-phenanthroline, then 2mL of acetonitrile is added, and finally 0.9mmol of 3-methylphenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under 365nm UV light and monitored by TLC. Finally, the final product 6-chloro-3- (m-tolyl) -1H-isochroman-1-one is obtained by column chromatography separation, and the yield is 67 percent, and the reaction equation is as follows:
EXAMPLE preparation of octa 3- (4-methoxyphenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 1mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of cesium carbonate, 1 equivalent of KI, 20mmol% of 2,2-bipyridine, 2mL of toluene and finally 0.9mmol of 4-methoxyphenylacetylene. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally toThe final product 3- (4-methoxyphenyl) -1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 71 percent, and the reaction equation is as follows:
EXAMPLE preparation of methyl 4- (1-oxo-1H-isochroman-3-yl) benzoate
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 5mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of triethylamine, 1 equivalent of I 2 20mmol% triphenylphosphine, 2mL DMSO, and finally 0.9mmol methyl 4-ethynylbenzoate. Then gas replacement is carried out to ensure that no water and no oxygen exist. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 4- (1-oxo-1H-isochroman-3-yl) methyl benzoate is obtained by column chromatography separation, and the yield is 65 percent, and the reaction equation is as follows:
EXAMPLE preparation of deca 3- (4-n-butylphenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 6mmol% of polyacid catalyst H 3 [PMo 12 O 40 ]0.9mmol of potassium tert-butoxide, 1 equivalent of I 2 20mmol% of L-proline, then adding 2mL of N, N-dimethylformamide, and finally adding 0.9mmol of 4-butyl phenylacetylene. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under illumination with 310nm UV light and monitored by TLC. Finally, the final product 3- (4-N-butylphenyl) -1H-isochroman-1-one in a yield of 65%, the reaction equation is as follows:
EXAMPLE preparation of eleven 3- (4-tert-butylphenyl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 4mmol% of polyacid catalyst H 3 [PMo 12 O 40 ]0.9mmol of sodium tert-butoxide, 1 equivalent of KI, 20mmol% of 1,10-phenanthroline, then 2mL of acetonitrile is added, and finally 0.9mmol of 4-tert-butyl phenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under 365nm UV light and monitored by TLC. Finally, the final product 3- (4-tert-butylphenyl) -1H-isochroman-1-one is obtained by column chromatography, the yield being 64%, the reaction equation being as follows:
EXAMPLE preparation of twelve 3- ([ 1,1-biphenyl ] -4-yl) -1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 2-iodobenzoic acid and 4mmol% of polyacid catalyst Na 12 [α-P 2 W 15 O 56 ]·24H 2 O, 0.9mmol of potassium carbonate, 1 equivalent of KI, 20mmol% of 1,10-phenanthroline, then 2mL of DMSO is added, and finally 0.9mmol of 4-acetylenediphenyl is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 3- ([ 1,1-biphenyl) is obtained by column chromatography separation]-4-yl) -1H-isochroman-1-one in 61% yield according to the following equation:
EXAMPLE thirteen preparation of 7-fluoro-3-phenyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 5-fluoro-2-iodobenzoic acid and 2mmol% of polyacid catalyst Na 12 [α-P 2 W 15 O 56 ]·24H 2 O, 0.9mmol of cesium carbonate, 1 equivalent of NaI, 20mmol% of 2,2-bipyridine, then 2mL of N, N-dimethylformamide was added, and finally 0.9mmol of phenylacetylene was added. Then gas replacement is carried out to ensure that no water and no oxygen exist. The reaction was carried out for 36h under illumination with 310nm UV light and monitored by TLC. Finally, the final product 7-fluoro-3-phenyl-1H-isochroman-1-one is obtained by column chromatography separation, and the yield is 74 percent, and the reaction equation is as follows:
EXAMPLE preparation of tetradec 6-fluoro-3-phenyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 4-fluoro-2-iodobenzoic acid and 2mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Ce 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of lithium tert-butoxide, 1 equivalent of I 2 20mmol% of L-proline, then 2mL of tetrahydrofuran is added, and finally 0.9mmol of phenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 6-fluoro-3-phenyl-1H-isochroman-1-one is obtained by column chromatography separation, and the yield is 73 percent, and the reaction equation is as follows:
EXAMPLE fifteen preparation of 7-bromo-3-phenyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and then adding 0.3mmol of 5-bromo-2-iodobenzoic acid and 5mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Ce 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of tripotassium phosphate, 1 equivalent of KI and 20mmol percent of triphenylphosphine, then adding 2mL of toluene, and finally adding 0.9mmol of phenylacetylene. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under 365nm UV light illumination and monitored by TLC. Finally, the final product 7-bromo-3-phenyl-1H-isochroman-1-one is obtained by column chromatography separation, and the yield is 61 percent, and the reaction equation is as follows:
EXAMPLE preparation of hexadeca 7-iodo-3-phenyl-1H-isochroman-1-one
Adding a magnetic stirrer into a quartz reaction tube, and adding 0.3mmol of 2,5-diiodobenzoic acid and 10mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Ce 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of triethylamine, 1 equivalent of KI, 20mmol% of L-proline, then adding 2mL of DMSO, and finally adding 0.9mmol of phenylacetylene. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under illumination with 310nm UV light and monitored by TLC. Finally, the final product 7-iodine-3-phenyl-1H-isochroman-1-ketone is obtained by column chromatography separation, and the yield is 53 percent, and the reaction equation is as follows:
EXAMPLE preparation of heptadeca-5-methyl-3-phenyl-1H-isochroman-1-one
Taking a quartz reaction tube, adding a magnetic stirrer, and adding 0.3mmol of 2-iodine-3-methylbenzoic acid and 10mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of cesium carbonate, 1 equivalent of I 2 20mmol% 1,10-phenanthroline, then 2mL of N, N-dimethylformamide is added, and finally 0.9mmol phenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 5-methyl-3-phenyl-1H-isochroman-1-ketone is obtained by column chromatography separation, and the reaction equation with the yield of 75 percent is as follows:
EXAMPLE preparation of eighteen 7-methoxy-3-phenyl-1H-isochroman-1-one
Adding a magnetic stirrer into the quartz reaction tube, adding 0.3mmol of 2-iodine-5-methoxybenzoic acid and 5mmol% of polyacid catalyst [ H ] 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O, 0.9mmol of cesium carbonate, 1 equivalent of KI, 20mmol% of L-proline, then 2mL of DMSO is added, and finally 0.9mmol of phenylacetylene is added. Then gas replacement is carried out to ensure that no water or oxygen exists. The reaction was carried out for 36h under irradiation of UV light at 254nm and monitored by TLC. Finally, the final product 7-methoxy-3-phenyl-1H-isochroman-1-ketone is obtained by column chromatography separation, and the reaction equation with the yield of 71 percent is as follows:
the above-described embodiments are merely preferred embodiments of the present invention, and not intended to limit the scope of the invention, so that equivalent variations or modifications in the structure, characteristics and principles of the invention described in the claims should be included.
Claims (10)
1. A method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid is characterized by comprising the following steps:
under the conditions of room temperature, alkaline environment, iodine source and protective gas, in a solvent, catalyzing a compound shown as a formula I and a compound shown as a formula II to react by using ultraviolet lamp light-assisted polyacid catalyst, and synthesizing isocoumarin shown as a formula III:
wherein: r 1 Selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy; r 2 Selected from hydrogen, fluorine, chlorine, bromine, methyl, methoxy, methyl formate, n-butyl, tert-butyl, phenyl;
the polyacid catalyst is a photosensitive catalyst which can absorb under the light of ultraviolet light.
2. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the molar ratio of the compound represented by the formula I to the compound represented by the formula II is 1:3.
3. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the reaction provides a basic environment by using a base selected from any one of cesium carbonate, tripotassium phosphate, potassium carbonate, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide and triethylamine; the molar ratio of the base to the compound of formula I is 3:1.
4. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 3, wherein a ligand is added in the reaction, and the ligand is used for adjusting acid-base equilibrium so that the reaction is always in an alkaline condition.
5. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 4, wherein the ligand is any one of L-proline, 1,10-phenanthroline, 2,2-bipyridine and triphenylphosphine, and the addition amount of the ligand is 20mol% of the compound shown in formula I.
6. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the iodine source is KI, naI or I 2 In the above formula I, the amount of the iodine source added is 1 equivalent to that of the compound represented by formula I.
7. The method for synthesizing isocoumarin with high selectivity under polyacid catalysis according to claim 1, wherein the solvent is one selected from dimethyl sulfoxide, acetonitrile, toluene, tetrahydrofuran and N, N-dimethylformamide, and the ratio of the added amount of the solvent to the compound represented by formula I is as follows: compound represented by formula I solvent =3mmol, 20ml.
8. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the ultraviolet lamp light is 200-400 nm ultraviolet lamp light.
9. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the polyacid catalyst is selected from H 3 [PMo 12 O 40 ]、Na 10 [α-SiW 9 O 34 ]·18H 2 O、H 6 [P 2 W 18 O 62 ]、Na 12 [α-P 2 W 15 O 56 ]·24H 2 O、
[H 2 N-CH 3 ) 2 ] 6 Na 4 [Pr 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 O、[H 2 N-CH 3 ) 2 ] 6 Na 4 [Ce 4 SeW 8 (H 2 O) 14 (H 2 PTCA) 2 O 28 ][SeW 9 O 33 ] 2 ·31H 2 And O, wherein the addition amount of the polyacid catalyst is 1-10 mol% of the compound shown in the formula I.
10. The method for synthesizing isocoumarin with high selectivity under the catalysis of polyacid according to claim 1, wherein the protective gas is nitrogen.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105218506A (en) * | 2015-09-15 | 2016-01-06 | 湖南大学 | A kind of method being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne |
| CN106588851A (en) * | 2016-11-29 | 2017-04-26 | 南阳师范学院 | Method of synthesizing isocoumarin derivatives by catalyzing tandem reaction in water phase |
| CN112321553A (en) * | 2020-10-30 | 2021-02-05 | 天津科技大学 | Method for synthesizing 3-position difluoromethyl substituted coumarin derivative from aryl alkyne acid ester |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218506A (en) * | 2015-09-15 | 2016-01-06 | 湖南大学 | A kind of method being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne |
| CN106588851A (en) * | 2016-11-29 | 2017-04-26 | 南阳师范学院 | Method of synthesizing isocoumarin derivatives by catalyzing tandem reaction in water phase |
| CN112321553A (en) * | 2020-10-30 | 2021-02-05 | 天津科技大学 | Method for synthesizing 3-position difluoromethyl substituted coumarin derivative from aryl alkyne acid ester |
Non-Patent Citations (5)
| Title |
|---|
| TUOPING LUO ET AL: "Syntheses of α-Pyrones Using Gold-Catalyzed Coupling Reactions", ORGANIC LETTERS, vol. 13, no. 11, pages 2834 * |
| YASHARSOLTANI ET AL: "Stoichiometric and Catalytic C-C and C-H Bond Formation with B(C6F5)3 via Cationic Intermediates", ANGEW.CHEM.INT.ED., vol. 56, pages 11995 - 11999 * |
| YI WANG ET AL: "A Facile, General Synthesis of 3, 4-Difluoro-6-substituted-2-pyrones", J.ORG.CHEM., vol. 71, pages 3859 * |
| 史作冬 等: "光催化乌尔曼型偶联反应研究进展", 化学研究, vol. 32, no. 4, pages 318 - 324 * |
| 唐建生 等: "溴化铁催化合成异香豆素", 合成化学, vol. 19, no. 2, pages 258 - 260 * |
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