CN117550975A - 一种多氟芳基或杂芳基衍生物的制备方法 - Google Patents
一种多氟芳基或杂芳基衍生物的制备方法 Download PDFInfo
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- CN117550975A CN117550975A CN202311571391.8A CN202311571391A CN117550975A CN 117550975 A CN117550975 A CN 117550975A CN 202311571391 A CN202311571391 A CN 202311571391A CN 117550975 A CN117550975 A CN 117550975A
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- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- 229940125782 compound 2 Drugs 0.000 claims abstract description 14
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 13
- 239000011701 zinc Substances 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 238000006880 cross-coupling reaction Methods 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 238000006114 decarboxylation reaction Methods 0.000 claims abstract description 5
- -1 p-toluenesulfonyl Chemical group 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 3
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 307
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 196
- 239000007787 solid Substances 0.000 description 91
- 239000003480 eluent Substances 0.000 description 80
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
- 238000002844 melting Methods 0.000 description 60
- 230000008018 melting Effects 0.000 description 60
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000003153 chemical reaction reagent Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 239000011734 sodium Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000001308 synthesis method Methods 0.000 description 8
- IUEBLRVJFPWJEG-UHFFFAOYSA-L zinc;2,3,4,5,6-pentafluorobenzoate Chemical class [Zn+2].[O-]C(=O)C1=C(F)C(F)=C(F)C(F)=C1F.[O-]C(=O)C1=C(F)C(F)=C(F)C(F)=C1F IUEBLRVJFPWJEG-UHFFFAOYSA-L 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 5
- 150000002989 phenols Chemical class 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 150000003751 zinc Chemical class 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- LUYQYZLEHLTPBH-UHFFFAOYSA-N perfluorobutanesulfonyl fluoride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O LUYQYZLEHLTPBH-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 150000001503 aryl iodides Chemical class 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical class CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- IMUSLIHRIYOHEV-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C IMUSLIHRIYOHEV-ZETCQYMHSA-N 0.000 description 1
- OHZAHWOAMVVGEL-UHFFFAOYSA-N 2,2'-bithiophene Chemical compound C1=CSC(C=2SC=CC=2)=C1 OHZAHWOAMVVGEL-UHFFFAOYSA-N 0.000 description 1
- FMMWHPNWAFZXNH-UHFFFAOYSA-N Benz[a]pyrene Chemical group C1=C2C3=CC=CC=C3C=C(C=C3)C2=C2C3=CC=CC2=C1 FMMWHPNWAFZXNH-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- DTXVEMGTMOSWBL-UHFFFAOYSA-N OC1(CC=CC=C1)C=1N=NNC1 Chemical compound OC1(CC=CC=C1)C=1N=NNC1 DTXVEMGTMOSWBL-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- 229940122016 Pim kinase inhibitor Drugs 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001499 aryl bromides Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- TWJVNKMWXNTSAP-UHFFFAOYSA-N azanium;hydroxide;hydrochloride Chemical class [NH4+].O.[Cl-] TWJVNKMWXNTSAP-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VRQXRVAKPDCRCI-ZNMIVQPWSA-N n-[4-[(1r,3s,5s)-3-amino-5-methylcyclohexyl]pyridin-3-yl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide Chemical compound C1[C@H](C)C[C@H](N)C[C@@H]1C1=CC=NC=C1NC(=O)C1=CC=C(F)C(C=2C(=CC=CC=2F)F)=N1 VRQXRVAKPDCRCI-ZNMIVQPWSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 125000005636 nonafluorobutanesulfonate group Chemical group 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/52—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
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Abstract
本发明公开了一种多氟芳基或杂芳基衍生物的制备方法，所述制备方法包括：在反应容器中加入式1所示的多氟苯甲酸锌盐、化合物2、催化剂和有机溶剂，所述催化剂为Pd(PPh3)4、Pd(OAc)2/PPh3或Pd(TFA)2/PPh3，于60‑100℃下经过脱羧和交叉偶联得到式3所示的多氟芳基或杂芳基衍生物。本发明提供的制备方法反应底物适用范围广、反应条件温和、收率高。
Description
技术领域
本发明属于有机合成领域，尤其涉及到一种多氟芳基或杂芳基衍生物的制备方法。
背景技术
含氟化合物由于其独特的物理和化学性质，引起了各学科科学家的极大兴趣和关注。其中，多氟(杂)芳基是药物化学、功能材料和配体中普遍存在的特性基团。很多使用的例子包括非甾体抗炎药二氟尼萨尔、PIM激酶抑制剂PIM447、液晶显示器、有机发光二极管等电子设备和单膦配体AIPhos。但是，有效地在分子中引入多氟(杂)芳基一直是一个重要的难题。
过渡金属催化的交叉偶联反应无疑是引入多氟(杂)芳基的有效方法。通常，这些策略主要包括(i)过渡金属催化的芳基卤化物和多氟芳基有机金属，如硼酸、格氏试剂、铜物种或锡之间的C-C偶联；(ii)多氟芳烃中C-F键的选择性芳基化；(iii)多氟芳烃的直接C-H活化和官能化和(iv)脱羧基交叉偶联。
近年来，脱羧交叉偶联作为一种可行的合成二芳基化合物的策略，引起了人们的极大关注。该策略使用稳定且易于获得的芳香族羧酸或羧酸盐作为芳基部分的来源，有效地避免了使用昂贵且敏感的有机金属试剂。例如，刘及其同事[Copper-catalyzeddecarboxylative cross-coupling ofpotassiumpolyfluorobenzoates with aryliodides andbromides.Angew Chem Int Ed Engl.2009；48(49):9350-4.doi:10.1002/anie.200904916.]即通过使用多氟苯甲酸钾和芳基卤化物，铜催化合成多氟二芳基，该方法在反应物为芳基碘化物时取得了高收率，但是当反应物为芳基溴化物时，则需要在反应体系中加入1,10-菲罗啉作为配体才能获得良好的反应收率。钯和镍催化也被用于构建多氟化二芳基。然而，这些反应受到二氧化碳挤出的极高温度要求的限制，会导致不希望的副反应，这限制了该方法在实践中的可行性。
发明内容
本发明的目的在于提供一种多氟芳基或杂芳基衍生物的制备方法，该制备方法反应底物适用范围广、反应条件温和、收率高。
为实现上述发明目的，本发明采用如下技术方案：
一种多氟芳基或杂芳基衍生物的制备方法，包括：在反应容器中加入式1所示的多氟苯甲酸锌盐、化合物2、催化剂和有机溶剂，所述催化剂为Pd(PPh3)4、Pd(OAc)2/PPh3或Pd(TFA)2/PPh3，于60-100℃下经过脱羧和交叉偶联得到式3所示的多氟芳基或杂芳基衍生物；
式1中，n为自然数，取值范围为2-5，R1为H、C1-C4的烷氧基、-COOR2、硝基或苯基，其中R2为C1-C4的烷基；并且，当n＝2时，R1不为H；
式2中，Ar为芳基或杂芳基，所述的芳基或杂芳基未被取代或者被取代；X为Br或ONf(即九氟丁烷磺酸酯基团)；m为自然数，m≥1；
式3中，当m＝1时，x＝1；当m≥2时，x≥1。
本发明所述的多氟苯甲酸锌盐，一般来说，二氟、三氟和四氟苯甲酸锌盐的反应效率低于五氟苯甲酸锌。但是，通过取代基修饰，可以提高二氟、三氟和四氟苯甲酸锌盐的反应性能。故作为优选，n为2、3或4时，R1为C1-C4的烷氧基、-COOR2、硝酸或苯基。最优选所述的多氟苯甲酸锌盐为五氟苯甲酸锌盐。
本发明所述的化合物2，其中的Ar可以是芳基或杂芳基。所述的芳基可以是苯基或多环芳基，所述的多环芳基可以是联苯基等非稠合多环芳基，也可以是萘、菲、蒽、芴、苯并芘等稠合多环芳基。所述的杂芳基可以是五元或六元的单杂芳基；也可以是非稠合多环杂芳基，所述的非稠合多环杂芳基包括联二噻吩等杂环和杂环连接形成的基团，以及苯环和杂环连接形成的基团；还可以是稠合杂芳基，所述稠合杂芳基包括苯环与杂环稠合的苯稠杂环基以及杂环与杂环稠合的稠杂环基。所述的芳基和杂芳基上除了取代基X外，可以不含其他取代基，也可以含有至少一个其他取代基。所述的取代基可以是氰基、硝基、C1-C10烷基、C1-C10烷氧基、C1-C10烷硫基、-COR3、-COOR4、-SO2R5、取代烷基、取代烯基、羟基等；其中R3选择H、C1-C10烷基或(X)m-Ar’-；R4选择C1-C10烷基；R5选择(X)m-Ar’-；所述的取代烷基是指C1-C10烷基中的至少一个H被取代，取代基各自独立选自-COOR6、苯基、对甲苯磺酰基(Ts)、酰胺基或BocNH-，其中R6选择C1-C10烷基；所述取代烯基是指C2-C10烯基中的至少一个烯基H被取代基取代，所述取代基为(X)m-Ar’-；所述Ar’是Ar-(X)m中的Ar去掉一个H形成的基团。
本发明中，所述的有机溶剂可以是DMF、乙腈、DMA、NMP、THF、二氧六环中的至少一种。作为优选，所述有机溶剂为DMF。
本发明中，所述的催化剂优选Pd(PPh3)4。
本发明中，所述化合物2与催化剂的投料摩尔比为1：0.005-0.20，优选1：0.05。
本发明中，一般若要实现化合物2中所有X取代基均发生反应，式1所示的多氟苯甲酸锌盐和化合物2的投料摩尔比需保持在m以上，大部分化合物2在投料摩尔比为m、反应温度为60℃时即可使m个X都发生反应获得较高的收率，但部分化合物(如邻位取代的底物)受到空间位阻的影响，需要提高多氟苯甲酸锌盐和化合物2的投料摩尔比和/或反应温度，才能使m个X都发生反应获得满意的收率，甚至于个别化合物由于空间位阻只能在邻位实现单取代，无法同时实现多取代。
本发明所述反应一般在惰性气氛(如氩气、氮气)下进行，在反应完全后，所得反应液可通过如下操作分离得到产物：反应液中加入饱和氯化铵水溶液淬灭，用乙酸乙酯萃取，有机层分离后用硫酸钠干燥，过滤，真空蒸发；再用硅胶柱层析(洗脱试剂优选正己烷或者正己烷和乙酸乙酯的混合液)纯化得到产物。
与现有技术相比，本发明的有益效果在于：本发明所述多氟芳基或杂芳基衍生物的制备方法，反应条件温和，收率高；反应无需事先合成敏感的金属试剂，节省操作步骤和操作难度，易于工业化放大；反应原料廉价易得，多氟苯甲酸都可商品化；底物适用范围广，底物敏感官能团兼容性好，氨基酸或多肽都可以进行反应；反应底物可设计性强，可根据实际需要设计合成出各种不同取代多氟芳基衍生物，实用性较强；本发明制备得到的多氟芳基或杂芳基衍生物在液晶显示器和有机发光二极管等电子设备、药物等领域有广泛的用途。
具体实施方式
下面以具体实施例对本发明的技术方案做进一步说明，但本发明的保护范围不限于此。
本发明实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过常规技术手段获得或者通过市购获得的常规产品。
本发明所述的多氟苯甲酸锌盐可通过多氟苯甲酸与氢氧化锌反应获得，所述的Ar-(ONf)m通常可由相应的酚类化合物Ar-(OH)m与九氟丁烷磺酰氟反应获得。
实施例0：多氟苯甲酸锌盐的合成
将多氟苯甲酸(10mmol)、Zn(OH)2(5mmol)和去离子水(50mL)的混合物加入到100mL圆底烧瓶中。将反应烧瓶在50℃下搅拌5小时。完成后，将混合物蒸发并在50℃真空下干燥6小时，以提供相应的多氟苯甲酸锌盐1a、1b、1c、1d、1e、1f、1g。
2,3,4,5,6-五氟苯甲酸锌(1a)
13C NMR(100MHz,D2O)δ165.07,143.03(dm,JC-F＝247.8Hz),141.12(dm,JC-F＝253.2Hz),137.27(dm,JC-F＝252.3Hz),113.40(t,JC-F＝21.9Hz).
19F NMR(376MHz,D2O)δ-142.68–-147.85(m,4F),-155.35(t,J＝20.7Hz,2F),-160.95–-162.97(m,4F).
2,3,5,6-四氟苯甲酸锌(1b)
1H NMR(400MHz,D2O)δ7.39–7.13(m,2H).
13C NMR(100MHz,D2O)δ166.15(t,JC-F＝2.5Hz),145.61(dm,JC-F＝248.3Hz),142.22(dm,JC-F＝246.1Hz),119.30(t,JC-F＝22.0Hz),105.94(t,JC-F＝23.1Hz).
19F NMR(376MHz,D2O)δ-138.83–-139.68(m,4F),-144.54–-144.96(m,4F).
2,3,5,6-四氟-4-甲氧基苯甲酸锌(1c)
1H NMR(400MHz,D2O)δ4.03(s,6H).
13C NMR(100MHz,D2O)δ166.06,144.67–144.26(m),142.27–141.54(m),139.52–139.15(m),138.06–137.65(m),112.31(t,JC-F＝22.1Hz),62.24(t,JC-F＝3.6Hz).
19F NMR(376MHz,D2O)δ-145.50(dd,J＝21.5,7.6Hz,4F),-157.83(dd,J＝22.3,8.3Hz,4F).
2,3,5,6-四氟-4-(甲氧基甲酰基)苯甲酸锌(1d)
1H NMR(400MHz,D2O)δ3.94(s,6H).
13C NMR(100MHz,D2O)δ164.76,161.92,147.53–144.97(m),144.83–142.12(m),142.12–138.89(m),122.36(t,JC-F＝22.8Hz),110.80(t,JC-F＝14.7Hz),53.60.
19F NMR(376MHz,D2O)δ-136.20–-140.69(m,4F),-141.75–-145.62(m,4F).
2,4,6-三氟苯甲酸锌(1e)
1H NMR(400MHz,D2O)δ6.81(dd,J＝13.5,8.7Hz,4H).
13C NMR(100MHz,D2O)δ168.36,162.12(dt,JC-F＝248.0,15.6Hz),159.06(ddd,JC-F＝247.7,15.5,11.5Hz),116.05–110.57(m),106.81–96.25(m).
19F NMR(376MHz,D2O)δ-108.07(dd,J＝13.9,7.1Hz,2F),-111.02–-116.60(m,4F).
2,6-二氟-3-硝基苯甲酸锌(1f)
1H NMR(400MHz,D2O)δ8.27–7.81(m,2H),7.11(t,J＝8.6Hz,2H).
13C NMR(100MHz,D2O)δ166.03,161.66(dd,JC-F＝258.3,8.2Hz),152.69(dd,JC-F＝264.6,10.1Hz),133.69(dd,JC-F＝7.7,4.0Hz),127.39(dd,JC-F＝11.4,1.8Hz),118.89(t,JC-F＝25.5Hz),112.61(dd,JC-F＝24.4,4.1Hz).
19F NMR(376MHz,D2O)δ-98.38–-108.24(m,2F),-118.05(dt,J＝13.2,6.7Hz,2F).
2,3,5,6-四氟-4-苯基苯甲酸锌(1g)
1H NMR(400MHz,DMSO-d6)δ7.91–7.25(m,10H).
13C NMR(100MHz,DMSO-d6)δ161.97,143.16(dm,JC-F＝246.3Hz),142.70(dm,JC-F＝246.9Hz),130.09,129.43,128.79,126.80,119.31(dm,JC-F＝17.4Hz),118.76(dm,JC-F＝21.9Hz).
19F NMR(376MHz,DMSO-d6)δ-142.87(dd,J＝25.1,12.6Hz,4F),-144.14(dd,J＝25.2,12.7Hz,4F).
实施例1
在配有磁性搅拌棒的10mL Schlenk管中加入五氟苯甲酸锌1a(0.5mmol)、4-溴苯甲酸甲酯(0.5mmol)和Pd(PPh3)4(28.9mg，0.025mmol)。反应容器被排空，并充满氩气三次。然后，在氩气下，用注射器加入DMF(2.0mL)。将反应混合物在60℃下搅拌12h。反应完成后，所得反应液通过1H NMR分析测定其中产物收率，并通过如下方法分离产物：反应液中加入饱和氯化铵水溶液(20mL)淬灭，用乙酸乙酯(3×10mL)萃取。有机层分离后用硫酸钠干燥，过滤，真空蒸发。以正己烷/乙酸乙酯混合物(40:1)为洗脱液，用硅胶柱层析纯化，得到白色固体，收率为93％，熔点111.5–114.3℃。
2',3',4',5',6'-五氟-[1,1'-联苯]-4-甲酸酯(3a)：
1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.1Hz,2H),7.51(d,J＝7.8Hz,2H),3.96(s,3H).
13C NMR(100MHz,CDCl3)δ166.54,144.26(dm,JC-F＝248.6Hz),140.98(dm,JC-F＝255.0Hz),138.07(dm,JC-F＝252.1Hz),131.08,130.41,130.03,115.02(d,J＝16.8,3.2Hz),52.50.
19F NMR(376MHz,CDCl3)δ-142.77(dd,J＝23.1,8.3Hz,2F),-154.12(t,J＝20.8Hz,1F),-161.60(td,J＝22.2,8.2Hz,2F).
HRMS(ESI):m/z calculated for C14H8F5O2 +[M+H]+:303.0439,found:303.0453.
对比例1-4
改变锌盐和/或锌盐用量，其他同实施例1，反应收率见表1。
表1
a通过1H NMR分析测定(括号内分离得率)。
实施例2
按照表2所示改变催化剂，其他同实施例1，反应收率见表2。
表2
实施例3
按照表3改变反应温度，其他同实施例1，反应收率见表3。
表3
实施例4
按照表4改变2,3,4,5,6-五氟苯甲酸锌(1a)的投料量，其他同实施例1，结果见表4。
表4
实施例5
按照表5改变锌盐1、反应底物2-1、投料比、反应条件、洗脱液(洗脱液的选择详见表征部分)等条件中的至少一个，其他同实施例1，得到目标产物3，反应收率见表5。
表5
上述目标产物3b-3zh的表征如下：
白色固体，熔点72.6–74.7℃，洗脱液：正己烷/EtOAc＝40/1
1H NMR(400MHz,CDCl3)δ7.85(dd,J＝7.9,1.4Hz,1H),7.75(td,J＝7.7,1.4Hz,1H),7.62(td,J＝7.7,1.2Hz,1H),7.48(d,J＝7.8Hz,1H).
13C NMR(100MHz,CDCl3)δ144.32(dm,JC-F＝253.5Hz),141.92(dm,JC-F＝256.7Hz),137.99(dm,JC-F＝254.4Hz),133.53,133.15,131.76,130.24,130.19,116.99,114.17,112.60(td,JC-F＝18.4,4.1Hz).
19F NMR(376MHz,CDCl3)δ-136.06–-144.73(m,2F),-151.96(t,J＝21.1Hz,1F),-159.57–-168.01(m,2F).
HRMS(ESI):m/z calculated for C13H5F5N+[M+H]+:270.0337,found:270.0329.
白色固体，48.1–49.6℃，洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ9.93(s,1H),8.03(dd,J＝7.5,1.4Hz,1H),7.83–7.59(m,2H),7.39(d,J＝7.4Hz,1H).
13C NMR(100MHz,CDCl3)δ190.60,144.22(dm,JC-F＝248.0Hz),141.27(dm,JC-F＝255.7Hz),137.79(dm,JC-F＝254.2Hz),134.38,134.14,132.37,131.97,130.38,127.30,113.23(td,J＝18.9,4.0Hz).
19F NMR(376MHz,CDCl3)δ-140.95(dd,J＝22.8,7.9Hz,2F),-153.97(t,J＝20.9Hz,1F),-161.92(td,J＝22.4,7.7Hz,2F).
HRMS(ESI):m/z calculated for C13H6F5O+[M+H]+:273.0333,found:273.0339.
白色固体，熔点68.3–71.6℃，洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ7.80-7.71(m,2H),7.71-7.62(m,2H),7.59-7.55(m,2H),7.49-7.38(m,3H).
13C NMR(100MHz,CDCl3)δ196.39,143.99(dm,JC-F＝246.4Hz),140.75(dm,JC-F＝253.9Hz),139.16,137.61(dm,JC-F＝252.6Hz),137.00,133.33,132.10,131.41,130.52,130.12,129.13,128.48,126.32,115.04(td,JC-F＝18.5,4.0Hz).
19F NMR(376MHz,CDCl3)δ-139.32–-143.50(m,2F),-154.97(t,J＝20.6Hz,1F),-162.26(td,J＝22.6,22.1,8.1Hz,2F).
HRMS(ESI):m/z calculated for C19H10F5O+[M+H]+:349.0646,found:349.0656.
无色油，洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.17(dd,J＝7.8,1.5Hz,1H),7.64(td,J＝7.5,1.5Hz,1H),7.57(td,J＝7.6,1.4Hz,1H),7.33(d,J＝7.5Hz,1H),4.24(q,J＝7.1Hz,2H),1.24(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3)δ165.92,144.09(dm,JC-F＝245.7Hz),140.73(dm,JC-F＝253.3Hz),137.59(dm,JC-F＝251.6Hz),132.49,132.11,131.33,130.77,129.77,127.33,116.09(td,JC-F＝19.1,4.0Hz),61.40,14.04.
19F NMR(376MHz,CDCl3)δ-138.64–-143.95(m,2F),-155.87(t,J＝20.9Hz,1F),-161.96–-166.81(m,2F).
HRMS(ESI):m/z calculated for C15H10F5O2 +[M+H]+:317.0595,found:317.0594.
白色固体，熔点81.2–82.6℃，洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.25(dd,J＝8.2,1.3Hz,1H),7.88–7.75(m,1H),7.73–7.64(m,1H),7.45(d,J＝7.4Hz,1H).
13C NMR(100MHz,CDCl3)δ148.52,143.95(dm,JC-F＝248.6Hz),141.39(dm,JC-F＝249.0Hz),137.88(dm,JC-F＝254.0Hz),133.85,133.18,131.04,125.60,121.63,112.81(td,J＝18.5,4.3Hz).
19F NMR(376MHz,CDCl3)δ-141.29(dd,J＝22.2,7.4Hz,2F),-153.50(t,J＝20.8Hz,1F),-161.60(td,J＝21.8,7.0Hz,2F).
HRMS(ESI):m/z calculated for C12H5F5NO2 +[M+H]+:290.0235,found:290.0250.
白色固体，熔点44.5–47.9℃,洗脱液:正己烷/EtOAc＝100/1.
1H NMR(400MHz,CDCl3)δ7.57–7.40(m,1H),7.23(d,J＝7.4Hz,1H),7.13–6.98(m,2H),3.81(s,3H).
13C NMR(100MHz,CDCl3)δ157.25,144.55(dm,JC-F＝246.5Hz),140.66(dm,JC-F＝252.6Hz),137.72(dm,JC-F＝250.0Hz),131.86,131.27,120.76,115.38,112.87(td,JC-F＝19.0,3.7Hz),111.41,55.81.
19F NMR(376MHz,CDCl3)δ-137.43–-144.51(m,2F),-156.16(t,J＝20.8Hz,1F),-163.19(td,J＝22.3,7.8Hz,2F).
HRMS(ESI):m/z calculated for C13H8F5O+[M+H]+:275.0490,found:275.0507.
白色固体，熔点57.8–60.2℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ10.08(s,1H),8.05–7.90(m,2H),7.70–7.67(m,2H).
13C NMR(100MHz,CDCl3)δ191.54,144.32(dm,JC-F＝248.7Hz),141.01(dm,JC-F＝255.3Hz),138.06(dm,JC-F＝253.5Hz),136.96,136.03,131.50,130.57,129.74,127.68,114,67(td,JC-F＝16.9,4.0Hz).
19F NMR(376MHz,CDCl3)δ-143.04(dd,J＝22.9,8.2Hz,2F),-153.91(t,J＝21.1Hz,1F),-161.39(td,J＝22.4,8.3Hz,2F).
HRMS(ESI):m/z calculated for C13H6F5O+[M+H]+:273.0333found:273.0316.
白色固体，熔点97.3–99.2℃,洗脱液:正己烷/EtOAc＝30/1.
1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.4Hz,2H),7.54(d,J＝8.3Hz,2H),2.65(s,3H).
13C NMR(100MHz,CDCl3)δ197.46,144.25(dm,JC-F＝248.6Hz),140.99(dm,JC-F＝255.1Hz),138.05(dm,JC-F＝253.3Hz)137.61,131.19,130.61,128.69,115.01(td,JC-F＝16.9,4.1Hz),26.75.
19F NMR(376MHz,CDCl3)δ-142.81(dd,J＝22.5,8.2Hz,2F),-154.07(t,J＝20.8Hz,1F),-158.35–-166.64(m,2F).
HRMS(ESI):m/z calculated for C14H8F5O+[M+H]+:287.0490,found:287.0511.
白色固体，熔点141.1–143.2℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ7.93(d,J＝8.3Hz,2H),7.85(d,J＝6.8Hz,2H),7.63(t,J＝7.4Hz,1H),7.58-7.47(m,4H).
13C NMR(100MHz,CDCl3)δ196.07,144.29(dm,JC-F＝253.6Hz),141.00(dm,JC-F＝254.8Hz),138.09(dm,JC-F＝253.5Hz)138.37,137.28,132.94,130.54,130.40,130.34,130.23,128.60,115.10(td,JC-F＝16.7,3.7Hz).
19F NMR(376MHz,CDCl3)δ-142.73(dd,J＝22.6,8.0Hz,2F),-154.03(t,J＝20.9Hz,1F),-159.60--163.43(m,2F).
HRMS(ESI):m/z calculated for C19H10F5O+[M+H]+:349.0646,found:349.0657.
白色固体，熔点129.4–132.2℃,洗脱液:正己烷/EtOAc＝100/1.
1H NMR(400MHz,CDCl3)δ7.38–7.29(m,4H),2.53(s,3H).
13C NMR(100MHz,CDCl3)δ144.28(dm,JC-F＝247.4Hz),140.85,140.47(dm,JC-F＝245.4Hz),138.02(dm,JC-F＝247.8Hz),130.55,126.24,122.74,115.58(td,JC-F＝16.9,4.0Hz),15.40.
19F NMR(376MHz,CDCl3)δ-143.33(dd,J＝22.5,8.4Hz,2F),-155.74(t,J＝20.8Hz,1F),-162.21(td,J＝22.3,8.4Hz,2F).
HRMS(ESI):m/z calculated for C13H8F5S+[M+H]+:291.0261,found:291.0266.
白色固体，熔点192.6–194.8℃,洗脱液:正己烷/EtOAc＝100/1.
1H NMR(400MHz,CDCl3)δ7.68(d,J＝8.4Hz,2H),7.58(d,J＝8.8Hz,2H),7.48(d,J＝8.2Hz,2H),7.01(d,J＝8.8Hz,2H),3.87(s,3H).
13C NMR(100MHz,CDCl3)δ159.75,144.36(dm,JC-F＝244.1Hz),141.94,140.52(dm,JC-F＝241.0Hz),138.02(dm,JC-F＝248.4Hz),132.77,130.66,128.37,127.07,124.71,115.84(td,JC-F＝17.6,3.6Hz),114.51,55.51.
19F NMR(376MHz,CDCl3)δ-143.18(dd,J＝23.2,8.2Hz,2F),-155.66(t,J＝21.0Hz,1F),-161.06–-168.01(m,2F).
HRMS(ESI):m/z calculated for C19H12F5O+[M+H]+:351.0803,found:351.0807.
白色固体，熔点215.4–217.3℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ8.14(d,J＝6.7Hz,1H),8.08(d,J＝8.3Hz,2H),7.93(s,1H),7.66(d,J＝9.1Hz,1H),7.51(d,J＝8.4Hz,2H),7.23-7.18(m,1H),6.83-6.79(m,1H).
13C NMR(100MHz,CDCl3)δ145.89,144.84,144.31(dm,JC-F＝248.1Hz),140.47(dm,JC-F＝248.8Hz),137.99,(dm,JC-F＝252.8Hz),134.82,130.69,126.35,125.83,125.23,117.78.115.83,(dm,JC-F＝17.1,3.7Hz)112.88,108.78.
19F NMR(376MHz,CDCl3)δ-143.01(dd,J＝23.1,8.2Hz,2F),-155.59(t,J＝21.0Hz,1F),-159.64–-164.95(m,2F).
HRMS(ESI):m/z calculated for C19H10F5N2 +[M+H]+:361.0759found:361.0767.
白色固体，熔点82.4–84.3℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.14-6.65(m,3H),6.04(s,2H).
13C NMR(100MHz,CDCl3)δ148.62,148.14,144.38(dm,JC-F＝246.9Hz),140.35(dm,JC-F＝253.4Hz),137.98(dm,JC-F＝249.4Hz),124.41,119.59,115.82(td,JC-F＝16.9,3.9Hz),110.53,108.80,101.70.
19F NMR(376MHz,CDCl3)δ-143.19(dd,J＝22.7,8.1Hz,2F),-156.03(t,J＝21.2Hz,1F),-160.25–-165.88(m,2F).
HRMS(ESI):m/z calculated for C13H6F5O2 +[M+H]+:289.0282,found:289.0308.
白色固体，熔点89.7–92.1℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.99(dd,J＝20.1,8.1Hz,2H),7.67–7.40(m,5H).
13C NMR(100MHz,CDCl3)δ144.79(dm,JC-F＝247.5Hz),141.08(dm,JC-F＝253.7Hz),137.91(dm,JC-F＝252.6Hz),133.84,131.68,130.30,129.14,128.79,127.22,126.55,125.36,124.70,123.94,114.53(td,JC-F＝19.6,3.7Hz).
19F NMR(376MHz,CDCl3)δ-137.21–-145.42(m,2F),-154.66(t,J＝20.8Hz,1F),-159.34–-166.41(m,2F).
HRMS(ESI):m/z calculated for C16H8F5 +[M+H]+:295.0541,found:295.0551.
白色固体，熔点110.7–113.2℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.02(d,J＝8.2Hz,1H),7.93(d,J＝8.2Hz,1H),7.84(d,J＝7.5Hz,1H),7.58(t,J＝7.7Hz,1H),7.44(d,J＝7.2Hz,1H),7.35(t,J＝7.8Hz,1H).
13C NMR(100MHz,CDCl3)δ144.90(dm,JC-F＝245.0Hz),141.31(dm,JC-F＝253.3Hz),137.65(dm,JC-F＝251.6Hz),136.17,134.30,132.53,131.76,129.84,129.68,126.78,125.64,123.35,118.77,117.05(td,J＝19.5,4.0Hz).
19F NMR(376MHz,CDCl3)δ-139.97(dd,JC-F＝24.1,8.1Hz,2F),-155.48(t,J＝20.7Hz,1F),-163.39(td,J＝22.3,8.3Hz,2F).
HRMS(EI):m/z calculated for C16H6BrF5 ·+[M]·+:371.9568,found:371.9569.
白色固体，熔点165.2–167.7℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.05-7.82(m,4H),7.60-7.54(m,2H),7.50(dd,J＝8.5,1.7Hz,1H).
13C NMR(100MHz,CDCl3)δ144.50(dm,JC-F＝247.8Hz),140.60(dm,JC-F＝253.6Hz),138.07(dm,JC-F＝254.8Hz),133.42,133.19,130.26,128.58,128.45,127.92,127.35,127.16,126.86,123.88,116.12(td,JC-F＝17.2,3.9Hz).
19F NMR(376MHz,CDCl3)δ-143.00(dd,J＝23.3,8.2Hz,2F),-155.41(t,J＝20.8Hz,1F),-162.12(td,J＝22.2,8.2Hz,2F).
HRMS(ESI):m/z calculated for C16H8F5 +[M+H]+:295.0541,found:295.0551.
白色固体，熔点122.6–124.4℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.90–7.54(m,3H),7.33(dd,J＝8.5,1.6Hz,1H),6.84(d,J＝2.1Hz,1H).
13C NMR(100MHz,CDCl3)δ155.23,146.16,144.43(dm,JC-F＝246.8Hz),140.48(dm,JC-F＝240.4Hz),137.96(dm,JC-F＝241.0Hz),128.08,126.39,123.43,120.93,116.38(td,J＝17.4,4.0Hz),111.97,106.84.
19F NMR(376MHz,CDCl3)δ-143.21(dd,J＝22.8,8.1Hz,2F),-155.95(t,J＝21.0Hz,1F),-162.35(td,J＝22.3,8.0Hz,2F).
HRMS(ESI):m/z calculated for C14H6F5O+[M+H]+:285.0333,found:285.0353.
白色固体，熔点142.6–144.5℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.00(d,J＝8.4Hz,1H),7.89(s,1H),7.54(d,J＝5.5Hz,1H),7.48–7.34(m,2H).
13C NMR(100MHz,CDCl3)δ144.45(dm,JC-F＝247.6Hz),140.78,140.51(dm,JC-F＝253.8Hz),139.92,138.02(dm,JC-F＝247.8Hz),127.86,125.83,125.59,124.06,122.99,122.43,116.19(td,J＝17.2,3.9Hz).
19F NMR(376MHz,CDCl3)δ-143.08(dd,J＝23.4,8.2Hz,2F),-155.61(t,J＝20.8Hz,1F),-158.88–-166.41(m,2F).
HRMS(ESI):m/z calculated for C14H6F5S+[M+H]+:301.0105,found:301.0104.
白色固体，熔点154.7–157.9℃,洗脱液:正己烷/EtOAc＝5/1.
1H NMR(400MHz,CDCl3)δ9.34(s,1H),8.61(d,J＝5.8Hz,1H),8.10(d,J＝8.5Hz,1H),7.92(s,1H),7.71(d,J＝5.7Hz,1H),7.63(dd,J＝8.5,1.6Hz,1H).
13C NMR(100MHz,CDCl3)δ152.56,144.37(dm,JC-F＝251.0Hz),143.98,141.07(dm,JC-F＝255.4Hz),138.11(dm,JC-F＝251.5Hz),135.61,128.87,128.75,128.64,128.37,128.32,120.75,115.20(td,JC-F＝17.0,4.0Hz).
19F NMR(376MHz,CDCl3)δ-142.71(dd,J＝22.9,8.2Hz,2F),-153.75(t,J＝20.8Hz,1F),-161.33(td,J＝22.3,7.9Hz,2F).
HRMS(EI):m/z calculated for C15H6F5N·+[M]·+:295.0415,found:295.0415.
白色固体，熔点156.8–159.4℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.31-8.21(m,3H),8.20-8.10(m,3H),8.06(t,J＝7.6Hz,1H),7.93(d,J＝7.9Hz,1H),7.74(dt,J＝9.2,1.9Hz,1H).
13C NMR(100MHz,CDCl3)δ144.87(dm,JC-F＝248.6Hz),141.17(dm,JC-F＝254.3Hz),138.02(dm,JC-F＝253.7Hz),132.43,131.33,130.83,129.84,128.96,128.78,128.41,127.33,126.53,126.14,125.93,125.02,124.81,124.57,123.90,120.67,115.09(td,JC-F＝19.5,4.1Hz).
19F NMR(376MHz,CDCl3)δ-139.34(dd,J＝23.4,8.4Hz,2F),-154.49(t,J＝20.7Hz,1F),-160.90--163.37(m,2F).
HRMS(EI):m/z calculated for C22H9F5 ·+[M]·+:368.0619,found:368.0618.
白色固体，熔点236.6–237.8℃,洗脱液:正己烷/EtOAc＝10/1.
1H NMR(400MHz,CDCl3)δ8.44(d,J＝8.1Hz,1H),8.40(d,J＝1.6Hz,1H),8.38–8.30(m,2H),7.89–7.79(m,3H).
13C NMR(100MHz,CDCl3)δ182.64,182.56,144.27(dm,JC-F＝250.7Hz),141.38(dm,JC-F＝257.0Hz),138.12(dm,JC-F＝254.5Hz),135.66,134.60,134.58,133.87,133.72,133.49,133.47,132.56,129.25,127.93,127.55,127.52,114.29(td,JC-F＝16.7,4.0Hz).
19F NMR(376MHz,CDCl3)δ-142.37(dd,J＝22.9,8.2Hz,2F),-152.75(t,J＝21.1Hz,1F),-160.90(td,J＝22.4,21.7,7.3Hz,2F).
白色固体，熔点116.2–118.3℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.22–7.01(m,15H).
13C NMR(100MHz,CDCl3)δ148.19,144.32(dm,JC-F＝245.3Hz),142.46,141.09,140.63(dm,JC-F＝253.5Hz),139.94,137.52(dm,JC-F＝252.1Hz),130.96,129.91,129.22,128.28,128.20,128.05,127.95,127.65,127.47,124.99,118.32(td,JC-F＝18.7,3.1Hz).
19F NMR(376MHz,CDCl3)δ-136.52–-143.37(m,2F),-155.57(t,J＝20.9Hz,1F),-159.57–-166.87(m,2F).
HRMS(ESI):m/z calculated for C26H16F5 +[M+H]+:423.1167,found:423.1189.
白色固体，熔点146.6–149.0℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ7.97(d,J＝8.3Hz,4H),7.60(d,J＝8.4Hz,4H).
13C NMR(100MHz,CDCl3)δ195.21,144.29(dm,JC-F＝244.9Hz),141.05(dm,JC-F＝255.4Hz),138.10(dm,JC-F＝253.1Hz),137.85,130.93,130.49,130.41,114.98(td,J＝16.9,3.9Hz).
19F NMR(376MHz,CDCl3)δ-142.76(dd,J＝23.0,8.1Hz,2F),-153.91(t,J＝20.8Hz,1F),-161.47(td,J＝22.5,8.1Hz,2F).
HRMS(ESI):m/z calculated for C25H9F10O+[M+H]+:515.0488,found:515.0508.
白色固体，熔点139.2–142.8℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.03(d,J＝8.6Hz,2H),7.98(s,2H),7.59(dd,J＝8.5,1.6Hz,2H).
13C NMR(100MHz,CDCl3)δ144.51(dm,JC-F＝252.0Hz),140.78(d,JC-F＝254.5Hz),138.10(dm,JC-F＝251.4Hz),133.22,132.85,130.59,128.52,128.50,124.90,115.70(td,J＝17.2,4.2Hz).
19F NMR(376MHz,CDCl3)δ-142.92(dd,J＝23.0,8.2Hz,4F),-154.73(t,J＝21.0Hz,2F),-157.62–-169.13(m,4F).
HRMS(ESI):m/z calculated for C22H7F10 ·+[M]·+:460.0304,found:461.0306.
白色固体，熔点87.7–91.1℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.2Hz,2H),7.44(d,J＝7.7Hz,4H),2.06–1.95(m,4H),1.10(m,12H),0.84-0.64(m,10H).
13C NMR(100MHz,CDCl3)δ151.61,144.35(dm,JC-F＝247.6Hz),141.39,140.51(dm,JC-F＝237.8Hz),138.00(dm,JC-F＝234.3Hz),129.26,125.52,125.08,120.48,116.49(td,JC-F＝16.9,3.7Hz),55.68,40.20,31.50,29.69,23.86,22.61,14.05.
19F NMR(376MHz,CDCl3)δ-142.97(dd,J＝23.1,8.2Hz,4F),-155.80(t,J＝20.9Hz,2F),-162.26(td,J＝22.7,8.1Hz,4F).
HRMS(ESI):m/z calculated for C37H33F10 +[M+H]+:667.2417,found:667.2424.
白色固体，熔点159.0–161.1℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.78(s,2H).
13C NMR(100MHz,CDCl3)δ153.16,144.79(dm,JC-F＝250.0Hz),141.86(dm,JC-F＝256.1Hz),138.10(dm,JC-F＝254.0Hz),131.34,121.70,111.36(td,JC-F＝18.3,4.1Hz).
19F NMR(376MHz,CDCl3)δ-138.42–-140.48(m,4F),-152.53(t,J＝20.8Hz,2F),-161.18(dd,J＝21.2,14.4Hz,4F).
HRMS(ESI):m/z calculated for C18H2F10N2SNa+[M+Na]+:490.9671found:490.9680.
黄色固体，熔点176.9–178.2℃,洗脱液:正己烷/EtOAc＝80/1.
1H NMR(400MHz,CDCl3)δ7.50(d,J＝3.9Hz,2H),7.31(d,J＝4.0Hz,2H).
19F NMR(376MHz,CDCl3)δ-137.89–-140.70(m,2F),-155.29(t,J＝21.3Hz,1F),-160.48–-166.41(m,2F).
HRMS(ESI):m/z calculated for C20H4F11S2 +[M+H]+:498.9667,found:498.9672.
白色固体，熔点143.1–145.3℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.4Hz,2H),7.55(d,J＝8.5Hz,2H),7.17–7.03(m,1H),3.96(s,3H).
13C NMR(100MHz,CDCl3)δ166.63,146.40(dm,JC-F＝248.6Hz),143.71(dm,JC-F＝248.2Hz),132.13,130.94,130.37,129.91,120.63(t,JC-F＝16.3Hz),105.74(t,JC-F＝22.6Hz),52.48.
19F NMR(376MHz,CDCl3)δ-138.56(ddd,J＝22.2,12.4,9.4Hz,2F),-143.43(ddd,J＝20.9,12.7,7.2Hz,2F).
HRMS(EI-TOF):m/z calculated for C14H8F4O2 ·+[M]·+:284.0455,found:284.0454.
白色固体，熔点103.9–106.1℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.13(d,J＝8.4Hz,2H),7.51(d,J＝8.0Hz,2H),4.13(s,3H),3.95(s,3H).
13C NMR(100MHz,CDCl3)δ166.68,144.37(dm,JC-F＝247.1Hz),141.27(dm,JC-F＝247.6Hz),138.42-137.92(m),132.06,130.55,130.41,129.87,113.19(t,JC-F＝16.9Hz),62.30(t,JC-F＝3.9Hz),52.43.
19F NMR(376MHz,CDCl3)δ-144.80(dd,J＝21.6,9.1Hz,2F),-157.79(dd,J＝21.7,8.5Hz,2F).
HRMS(EI):m/z calculated for C15H10F4O3 ·+[M]·+:314.0561,found:314.0558.
白色固体，熔点135.2–137.3℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.17(d,J＝8.5Hz,2H),7.56(d,J＝8.4Hz,2H),4.01(s,3H),3.96(s,3H).
13C NMR(100MHz,CDCl3)δ166.49,160.20,145.05(dm,JC-F＝257.4Hz),143.99(dm,JC-F＝250.5Hz),131.39,131.18,130.30,130.02,122.83(t,JC-F＝16.6Hz),112.18(t,JC-F＝16.0Hz),53.55,52.56.
19F NMR(376MHz,CDCl3)δ-137.00–-141.41(m,2F),-141.41–-144.85(m,2F).
HRMS(EI):m/z calculated for C16H10F4O4 ·+[M]·+:342.0510,found:342.0507.
白色固体，熔点88.8–89.9℃,洗脱液:正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.05(d,J＝8.2Hz,2H),7.44(d,J＝7.9Hz,2H),6.74–6.68(m,2H),3.88(s,3H).
13C NMR(100MHz,CDCl3)δ166.86,162.35(dm,JC-F＝250.5Hz),160.35(dm,JC-F＝250.6Hz),133.23,130.49,130.12,129.71,114.26(m),100.85(m),52.40.
19F NMR(376MHz,CDCl3)δ-107.66(p,J＝7.2Hz,1F),-110.98(t,J＝7.6Hz,2F).
HRMS(EI):m/z calculated for C14H9F3O2 ·+[M]·+:266.0550,found:266.0547.
白色固体，熔点115.1–116.8℃,洗脱液:正己烷/EtOAc＝30/1.
1H NMR(400MHz,CDCl3)δ8.17-8.12(m,1H),7.53(d,J＝8.0Hz,2H),7.18-7.14(m,1H),3.95(s,3H).
13C NMR(100MHz,CDCl3)δ166.55,162.66(dd,JC-F＝260.3,5.9Hz),153.88(dd,JC-F＝267.5,7.7Hz),134.88(d,JC-F＝5.4Hz),131.58,131.05,130.42,129.92,126.85(d,JC-F＝11.3Hz),120.34(dd,JC-F＝20.0,17.9Hz),112.37(dd,JC-F＝24.8,4.3Hz),52.50.
19F NMR(376MHz,CDCl3)δ-101.06–-100.98(m,2F),-115.46(dd,J＝13.6,8.3Hz,2F).
HRMS(EI):m/z calculated for C14H9F2NO4 ·+[M]·+:293.0495,found:293.0493.
白色固体，熔点204.4–207.3℃,洗脱液：正己烷/EtOAc＝40/1.
1H NMR(400MHz,CDCl3)δ8.18(d,J＝8.3Hz,2H),7.61(d,J＝8.1Hz,2H),7.56–7.44(m,5H),3.97(s,3H).
13C NMR(100MHz,CDCl3)δ166.66,145.78–145.18(m),143.24–142.70(m),132.22,130.83,130.42,130.28,129.93,129.44,128.81,127.42,120.86–120.24(m),118.95–118.33(m),52.49.
19F NMR(376MHz,CDCl3)δ-143.67–-143.87(m),-143.87–-144.06(m).
HRMS(EI):m/z calculated for C20H12F4O2 ·+[M]·+:360.0768,found:360.0768.
实施例6
合成方法A:(4a-4j,4s-4w,4z)1
室温下，在酚类化合物(5.0mmol)和碳酸钾(829.2mg，6.0mmol)的MeCN(10mL)溶液中滴加九氟丁烷磺酰氟(2.3g，7.5mmol)。加入后，在室温下搅拌溶液12h。在反应混合物中加入水(30mL)和EtOAc(20mL)，分离有机层。含水层用乙酸乙酯(2×10mL)提取2次，合并有机提取物，用饱和食盐水(20mL)洗涤，用无水硫酸镁干燥，过滤，减压浓缩。粗产物经闪速层析纯化得到产物。
合成方法B:(4k-4o,4x)
在酚类化合物(5.0mmol)和碳酸钾(1.66g，12.0mmol)的MeCN(10mL)溶液中，在室温下滴加入九氟丁烷磺酰氟(4.6g，15.0mmol)。加入后，在室温下搅拌溶液12h。将反应混合物倒入50mL的水中。通过过滤收集得到的固体，依次用乙醇(5ml x 2)和乙醚(10ml x 2)洗涤，转移到圆底瓶中，在50℃真空干燥6小时以提供相应的产物。
合成方法C:(4p,4q,4y)
在室温下，在酚类化合物(5.0mmol)和碳酸钾(2.49g，18.0mmol)的MeCN(10mL)溶液中，滴加九氟丁烷磺酰氟(6.80g，22.5mmol)。加入后，在室温下搅拌溶液12h。将反应混合物倒入50mL的水中。通过过滤收集得到的固体，依次用乙醇(5ml x 2)和乙醚(10ml x 2)洗涤，转移到圆底瓶中，在50℃真空干燥6小时以提供相应的产物。
合成方法D:(4r)
在室温下，在酚类化合物(5.0mmol)和碳酸钾(3.32g，24.0mmol)的MeCN(10mL)溶液中滴加九氟丁烷磺酰氟化物(9.06g，30.0mmol)。加入后，在室温下搅拌溶液12h。将反应混合物倒入50mL的水中。通过过滤收集得到的固体，依次用乙醇(5ml x 2)和乙醚(10ml x2)洗涤，转移到圆底瓶中，在50℃真空下干燥6小时，以提供相应的产物4r。
合成方法E:(4za-4zc)
将盐酸(50mmol，12M)滴加入4z(5.91g，10mmol)的乙酸乙酯(50mL)溶液中，将反应混合物加热至室温，搅拌12h。反应混合物在真空中浓缩得到A，直接用于下一次反应，无需进一步纯化。
在0℃的A(1.06g、2.0mmol)的三氯甲烷(10mL)溶液中加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI，460.0mg、2.4mmol)、1-羟基苯基三唑(HOBt、27.0mg、0.2mmol)、N,N-二异丙基乙胺(646.2mg、5.0mmol)和N-Boc-L-氨基酸(2.0mmol)。将反应混合物加热至室温，并搅拌12小时。混合物用1M盐酸、饱和碳酸氢钠水溶液和饱和食盐水洗涤。有机层在无水硫酸钠上干燥，过滤，真空蒸发，用闪速层析纯化，得到产物。
合成方法F:(4zd,4ze)
将盐酸(50mmol，12M)滴加入4zc(7.39g，10mmol)的乙酸乙酯(50mL)溶液中，将反应混合物加热至室温，搅拌12h。反应混合物在真空中浓缩得到B，直接用于下一次反应，无需进一步纯化。
向B(1.35g，2.0mmol)的三氯甲烷(10mL)溶液中加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI，460.0mg、2.4mmol)、1-羟基苯并三唑(HOBt，27.0mg、0.2mmol)、N,N-二异丙基乙胺(666.2mg、5.0mmol)和N-Boc-L-氨基酸(2.0mmol)。将反应混合物加热至室温，并搅拌12小时。混合物用1M盐酸、饱和碳酸氢钠水溶液和饱和食盐水洗涤。有机层在无水硫酸钠上干燥，过滤，真空蒸发，用闪速层析纯化，得到产物。
合成方法G:(4zf)
将盐酸(10mmol，12M)滴加入0℃的C(1.45g，2.0mmol)的乙酸乙酯(10mL)溶液中，将反应混合物加热至室温，搅拌12h。反应混合物在真空中浓缩得到D，直接用于下一次反应，无需进一步纯化。
向0℃的D(1.32g、2.0mmol)的三氯甲烷(10mL)溶液中加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI，460.0mg、2.4mmol)、1-羟基苯并三唑(HOBt、27.0mg、0.2mmol)、N,N-二异丙基乙胺(646.2mg、5.0mmol)和N-Boc-L-蛋氨酸(2.2mmol)。将反应混合物加热至室温，并搅拌12小时。混合物用1M盐酸、饱和碳酸氢钠水溶液和饱和食盐水洗涤。有机层在无水硫酸钠上干燥，过滤，真空蒸发，用闪速层析纯化，得到产物4zf。
合成方法H:(4zg,4zh)
将盐酸(25mmol，12M)滴加入4zd(4.19g，5.0mmol)的EtOAc(25mL)溶液中，将反应混合物加热至室温，搅拌12h。反应混合物在真空中浓缩得到E，直接用于下一次反应，无需进一步纯化。
向E(1.55g，2.0mmol)的三氯甲烷(10mL)溶液加入1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐(EDCI，460.0mg、2.4mmol)、1-羟基苯并三唑(HOBt、27.0mg、0.2mmol)、N,N-二异丙基乙胺(646.2mg、5.0mmol)和N-Boc-L-氨基酸(2.2mmol)。将反应混合物加热至室温，并允许其搅拌12小时。混合物用1M盐酸、饱和碳酸氢钠水溶液和盐水洗涤。有机层在无水硫酸钠上干燥，过滤，真空蒸发，用闪速层析纯化，得到产物。
1.82g,90％收率,无色油,洗脱试剂:正己烷/EtOAc＝50/1.
1H NMR(400MHz,CDCl3)δ7.79(d,J＝7.7Hz,1H),7.77–7.70(m,1H),7.56–7.47(m,2H).
13C NMR(100MHz,CDCl3)δ150.00,134.92,134.61,128.89,122.73,113.62,107.55.
19F NMR(376MHz,CDCl3)δ-80.64(t,J＝9.6Hz,3F),-108.44(t,J＝14.0Hz,2F),-120.64(td,J＝9.0,4.6Hz,2F),-125.81(ddd,J＝14.1,6.1,3.0Hz,2F).
HRMS(ESI):m/z calculated for C11H5F9NO3S+[M+H]+:401.9841,found:401.9830.
1.79g,89％收率,无色油,洗脱试剂:正己烷/EtOAc＝50/1.
1H NMR(400MHz,CDCl3)δ8.01(dd,J＝7.7,1.8Hz,1H),7.79–7.67(m,1H),7.62–7.49(m,1H),7.43(d,J＝8.3Hz,1H).
13C NMR(100MHz,CDCl3)δ186.70,150.24,136.03,130.88,129.05,128.69,122.58.
19F NMR(376MHz,CDCl3)δ-78.57–-84.04(m,3F),-107.19–-112.80(m,2F),-119.44–-121.67(m,2F),-124.28–-127.61(m,2F).
HRMS(ESI):m/z calculated for C11H6F9O4S+[M+H]+:404.9838,found:404.9846.
2.04g,97％收率,白色固体,m.p.40.5–42.7℃,洗脱试剂:正己烷/EtOAc＝50/1.
1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.1Hz,1H),7.85–7.72(m,1H),7.60(t,J＝7.8Hz,1H),7.48(d,J＝8.3Hz,1H).
13C NMR(100MHz,CDCl3)δ141.93,141.85,135.59,129.48,126.82,124.35.
19F NMR(376MHz,CDCl3)δ-80.99(t,J＝9.8Hz,3F),-108.94(t,J＝13.8Hz,2F),-120.68–-121.34(m,2F),-125.97–-126.30(m,2F).
HRMS(ESI):m/z calculated for C10H5F9NO5S+[M+H]+:421.9739,found:421.9737.
1.91g,91％收率,无色油,洗脱试剂:正己烷/EtOAc＝50/1.
1H NMR(400MHz,CDCl3)δ7.81(dd,J＝7.7,1.6Hz,1H),7.65–7.56(m,1H),7.53–7.43(m,1H),7.35(d,J＝8.2Hz,1H),2.64(s,3H).
13C NMR(100MHz,CDCl3)δ196.93,147.08,133.82,132.39,130.84,128.70,122.90,29.52.
19F NMR(376MHz,CDCl3)δ-80.68(t,J＝9.7Hz,3F),-109.17(t,J＝13.9Hz,2F),-115.01–-122.76(m,2F),-122.38–-133.11(m,2F).
HRMS(ESI):m/z calculated for C12H8F9O4S+[M+H]+:418.9994,found:418.9997.
1.78g,88％收率,无色油,洗脱试剂:正己烷/EtOAc＝50/1.
1H NMR(400MHz,CDCl3)δ10.04(s,1H),8.00(d,J＝8.6Hz,2H),7.47(d,J＝8.6Hz,2H).
13C NMR(100MHz,CDCl3)δ190.25,153.61,136.02,131.86,122.38.
19F NMR(376MHz,CDCl3)δ-80.60(t,J＝9.7Hz,3F),-108.16–-109.53(m,2F),-120.74–-120.92(m,2F),-124.63–-126.61(m,2F).
HRMS(ESI):m/z calculated for C11H6F9O4S+[M+H]+:404.9838,found:404.9846.
3.07g,94％收率,白色固体,m.p.106.6–107.8℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.53–7.44(m,4H),7.40–7.29(m,3H),7.25(d,J＝1.8Hz,1H),7.20–7.08(m,4H),5.27(s,1H),3.87(s,3H),2.37(s,3H).
13C NMR(100MHz,CDCl3)δ151.48,145.03,139.08,134.99,134.80,132.51,129.94,129.56,129.14,129.11,129.01,122.70,122.45,117.24–109.64(m),75.88,56.41,21.67.
19F NMR(376MHz,CDCl3)δ-80.65(t,J＝9.7Hz,3F),-109.29–-110.69(m,2F),-120.15–-122.17(m,2F),-125.29–-126.64(m,2F).
HRMS(ESI):m/z calculated for C25H19F9O6S2Na+[M+Na]+:673.0372,found:673.0386.
1.96g,92％收率,白色固体,m.p.43.6–45.5℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.3Hz,1H),7.92(d,J＝8.1Hz,1H),7.91–7.84(m,1H),7.71–7.57(m,2H),7.54–7.43(m,2H).
13C NMR(100MHz,CDCl3)δ146.00,135.07,128.68,128.20,128.02,127.53,126.61,125.27,121.03,117.95.
19F NMR(376MHz,CDCl3)δ-80.61(t,J＝9.8Hz,3F),-103.16–-113.62(m,2F),-116.54–-123.11(m,2F),-122.74–-133.65(m,2F).
2.07mg,97％收率,无色油,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.96–7.82(m,3H),7.79(s,1H),7.65–7.52(m,2H),7.40(d,J＝9.0Hz,1H).
13C NMR(100MHz,CDCl3)δ147.51,133.50,132.51,130.71,128.17,128.04,127.68,127.31,119.68,119.39.
19F NMR(376MHz,CDCl3)δ-80.83(t,J＝9.8Hz,3F),-109.00(t,J＝13.9Hz,2F),-117.39–-123.48(m,2F),-123.92–-130.99(m,2F).
2.08g,99％收率,无色油,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ6.87–6.67(m,3H),6.04(s,2H).
13C NMR(100MHz,CDCl3)δ148.70,147.62,143.86,114.61,108.30,103.54,102.63.
19F NMR(376MHz,CDCl3)δ-80.85(t,J＝9.8Hz,3F),-100.62–-112.20(m,2F),-114.37–-123.49(m,2F),-123.78–-134.70(m,2F).
HRMS(ESI):m/z calculated for C11H6F9O5S+[M+H]+:420.9787,found:420.9788.
2.04g,92％收率,白色固体,m.p.81.9–83.8℃,洗脱试剂:正己烷/EtOAC＝4/1.
1H NMR(400MHz,CDCl3)δ7.67(d,J＝9.6Hz,1H),7.53(d,J＝8.6Hz,1H),7.19(s,1H),7.15(dd,J＝8.6,2.1Hz,1H),6.40(d,J＝9.6Hz,1H).
13C NMR(100MHz,CDCl3)δ159.38,154.63,151.14,142.30,129.59,118.90,117.79,117.75,110.50.
19F NMR(376MHz,CDCl3)δ-80.88(t,J＝9.7Hz,3F),-108.64(t,J＝13.7Hz,2F),-121.00(dd,J＝10.4,5.5Hz,2F),-125.66–-126.70(m,2F).
HRMS(ESI):m/z calculated for C13H6F9O5S+[M+H]+:444.9787,found:444.9796.
3.22g,89％收率,白色固体,m.p.38.2–39.7℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.95(s,2H),7.92(dd,J＝6.2,3.3Hz,2H),7.71–7.60(m,2H).
13C NMR(100MHz,CDCl3)δ138.45,131.94,128.87,128.27,122.20.
19F NMR(376MHz,CDCl3)δ-80.74(t,J＝9.7Hz,3F),-108.89(t,J＝13.6Hz,2F),-120.66–-120.88(m,2F),-125.78–-126.09(m,2F).
3.55g,94％收率,白色固体,m.p.85.9–87.2℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.3Hz,1H),7.92(d,J＝8.0Hz,1H),7.86(d,J＝2.3Hz,1H),7.70–7.41(m,3H).
13C NMR(100MHz,CDCl3)δ148.48,145.74,135.18,128.77,127.53,125.69,124.31,121.83,119.74,119.37.
19F NMR(376MHz,CDCl3)δ-79.91–-82.75(m,6F),-108.33–-108.83(m,2F),-108.88–-109.64(m,2F),-120.65–-120.77(m,2F),-120.77–-120.90(m,2F),-125.68–-126.03(m,4F).
3.38g,93％收率,白色固体,m.p.76.3–78.1℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ8.00(s,1H),7.98(s,1H),7.82(d,J＝2.2Hz,2H),7.49(d,J＝2.3Hz,1H),7.47(d,J＝2.3Hz,1H).
13C NMR(100MHz,CDCl3)δ148.65,133.76,131.38,130.90,121.30,119.66.
19F NMR(376MHz,CDCl3)δ-80.70(t,J＝9.8Hz,6F),-108.71(t,J＝13.8Hz,4F),-115.77–-123.14(m,4F),-123.52–-129.08(m,4F).
4.47g,98％收率,白色固体,m.p.106.1–107.6℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.83(d,J＝7.5Hz,2H),7.45(t,J＝7.1Hz,2H),7.40–7.32(m,4H),7.31–7.25(m,4H),7.23–7.12(m,4H).
13C NMR(100MHz,CDCl3)δ149.80,148.87,145.93,140.22,129.97,128.47,128.39,126.04,121.47,120.77,64.60.
19F NMR(376MHz,CDCl3)δ-80.69(t,J＝9.6Hz,3F),-109.00(t,J＝13.8Hz,2F),-120.38–-122.16(m,2F),-125.37–-126.70(m,2F).
HRMS(ESI):m/z calculated for C33H17F18O6S2 +[M+H]+:915.0174,found:915.0143.
3.86g,95％收率,白色固体,m.p.148.8–150.2℃,洗脱试剂:正己烷/EtOAc＝20/1.
1H NMR(400MHz,CDCl3)δ8.07(d,J＝8.9Hz,4H),7.47(d,J＝8.8Hz,4H).
13C NMR(100MHz,CDCl3)δ153.08,141.07,130.57,122.91.
19F NMR(376MHz,CDCl3)δ-80.69(t,J＝9.7Hz,3F),-108.17–-108.84(m,2F),-120.67–-121.22(m,2F),-125.67–-126.15(m,2F).
HRMS(ESI):m/z calculated for C20H9F18O8S3 +[M+H]+:814.9167,found:814.9168.
4.18g,86％收率,白色固体,m.p.102.9–105.2℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.35(s,3H).
13C NMR(100MHz,CDCl3)δ115.93,150.00.
19F NMR(376MHz,CDCl3)δ-80.61(t,J＝8.9Hz,3F),-107.71(t,J＝12.6Hz,2F),-120.63–-120.83(m,2F),-125.69–-125.96(m,2F).
HRMS(ESI):m/z calculated for C18H4F27O9S3 +[M+H]+:972.8581,found:972.8543.
5.19g,91％收率,白色固体,m.p.60.8–63.0℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.17(d,J＝8.7Hz,6H),7.06(d,J＝8.7Hz,6H),5.55(s,1H).
13C NMR(100MHz,CDCl3)δ148.89,142.68,131.15,121.92,54.92.
19F NMR(376MHz,CDCl3)δ-80.80(t,J＝9.7Hz,3F),-109.00(t,J＝13.7Hz,2F),-120.76–-121.51(m,2F),-125.70–-126.33(m,2F).
HRMS(ESI):m/z calculated for C31H14F27O9S3 +[M+H]+:1138.9363,found:1138.9382.
7.09g,93％收率,白色固体,m.p.138.3–139.4℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.15–6.98(m,16H).
13C NMR(100MHz,CDCl3)δ149.03,142.00,140.27,132.94,121.54.
19F NMR(376MHz,CDCl3)δ-80.71(t,J＝9.7Hz,3F),-108.89(t,J＝13.7Hz,2F),-116.45–-124.97(m,2F),-122.38–-133.49(m,2F).
HRMS(ESI):m/z calculated for C42H17F36O12S4 +[M+H]+:1524.9023,found:1524.9001.
1.83g,64％收率,白色固体,m.p.80.5–82.3℃,洗脱试剂:正己烷/EtOAc＝10/1.
1H NMR(400MHz,CDCl3)δ10.31(s,1H),8.52(d,J＝2.3Hz,1H),8.32(dd,J＝8.7,2.4Hz,1H),7.52(d,J＝8.7Hz,1H),4.37(q,J＝7.1Hz,2H),2.79(s,3H),1.40(t,J＝7.1Hz,4H).
13C NMR(100MHz,CDCl3)δ185.87,165.83,161.95,161.54,151.07,133.93,133.48,129.08,128.90,123.79,123.46,61.74,17.60,14.43.
19F NMR(376MHz,CDCl3)δ-80.56(t,J＝9.7Hz,3F),-107.86–-109.90(m,2F),-119.99–-121.64(m,2F),-125.38–-126.38(m,2F).
HRMS(ESI):m/z calculated for C18H13F9NO6S2 +[M+H]+:574.0035,found:574.0042.
1.66g,89％收率,白色固体,m.p.70.9–72.3℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ8.27(d,J＝2.3Hz,1H),8.17(dd,J＝9.0,2.3Hz,1H),7.85(d,J＝8.7Hz,2H),7.52(d,J＝9.0Hz,1H),7.40(d,J＝8.7Hz,2H),2.79(t,J＝7.7Hz,2H),1.78–1.58(m,2H),1.32–1.18(m,2H),0.81(t,J＝7.4Hz,3H).
13C NMR(100MHz,CDCl3)δ188.96,169.00,156.43,152.83,144.98,138.58,131.31,127.32,122.08,120.82,117.75,116.72,111.76,30.01,28.36,22.45,13.65.
19F NMR(376MHz,CDCl3)δ-80.62(t,J＝9.7Hz,3F),-106.54–-111.25(m,2F),-120.54–-121.32(m,2F),-125.54–-126.16(m,2F).
HRMS(ESI):m/z calculated for C23H17F9NO7S+[M+H]+:622.0577,found:622.0585.
1.26g,91％收率,白色固体,43.8–46.3℃,洗脱试剂:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.33(d,J＝8.6Hz,2H),7.26–7.16(m,4H),7.11(dd,J＝8.9,4.6Hz,2H),6.96–6.80(m,4H),4.74–4.39(m,2H),3.13–2.82(m,1H),2.14(brs,1H),1.99–1.74(m,4H).
13C NMR(100MHz,CDCl3)δ167.07,162.34(d,J＝245.7Hz),159.29(d,J＝244.1Hz),149.70,140.05(d,J＝3.0Hz),138.29,133.52(d,J＝2.6Hz),127.79,127.49(d,J＝8.1Hz),122.53,118.42(d,J＝7.9Hz),116.19(d,J＝22.7Hz),115.52(d,J＝21.5Hz),73.21,60.62,60.45,36.63,25.19.
19F NMR(376MHz,CDCl3)δ-80.60(t,J＝9.7Hz,3F),-108.84(t,J＝13.8Hz,2F),-114.49–-115.50(m,1F),-116.82–-118.62(m,1F),-120.67–-121.15(m,2F),-125.50–-126.04(m,2F).
HRMS(ESI):m/z calculated for C28H20F11NO5SNa+[M+Na]+:714.0779,found:714.0794.
2.54g,92％收率,白色固体,m.p.75.4–76.8℃,洗脱试剂:正己烷/EtOAc＝8/1.
1H NMR(400MHz,CDCl3)δ7.34(d,J＝8.7Hz,1H),7.04(dd,J＝8.7,2.4Hz,1H),7.00(s,1H),2.94(dd,J＝8.7,4.1Hz,2H),2.51(dd,J＝18.8,8.7Hz,1H),2.44–2.36(m,1H),2.35–2.25(m,1H),2.16(dd,J＝18.5,9.4Hz,1H),2.12–2.01(m,2H),2.01–1.93(m,1H),1.70–1.40(m,6H),0.92(s,3H).
13C NMR(100MHz,CDCl3)δ220.65,147.94,140.38,139.40,127.30,121.38,118.45,50.51,47.98,44.22,37.88,35.92,31.61,29.52,26.21,25.80,21.68,13.90.
19F NMR(376MHz,CDCl3)δ-80.66(t,J＝9.7Hz,3F),-104.21–-112.95(m,2F),-117.28–-122.36(m,2F),-123.78–-134.32(m,2F).
HRMS(ESI):m/z calculated for C22H22F9O5S+[M+H]+:553.1090,found:553.1096.
1.63g,88％收率,白色固体,m.p.241.4–244.4℃,洗脱试剂:正己烷/EtOAc＝1/1.
1H NMR(400MHz,DMSO-d6)δ8.74(s,1H),8.29(s,1H),8.22(d,J＝9.3Hz,1H),7.93–7.64(m,1H),7.30(s,1H),6.53(s,1H),5.39(s,2H),5.23(s,2H),2.07–1.64(m,2H),0.88(t,J＝7.1Hz,3H).
13C NMR(100MHz,DMSO-d6)δ172.38,156.66,154.04,149.90,147.13,146.62,144.75,131.93,131.90,131.12,128.05,123.78,120.31,119.75,97.24,72.34,65.25,50.21,30.40,7.74.
19F NMR(376MHz,DMSO-d6)δ-80.34(t,J＝9.3Hz,3F),-109.09(t,J＝13.1Hz,2F),-116.54–-124.16(m,2F),-123.11–-131.41(m,2F).
HRMS(ESI):m/z calculated for C24H16F9N2O7S+[M+H]+:647.0529,found:647.0539.
4.08g,98％收率,白色固体,m.p.108.5–110.2℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.38–7.22(m,8H),2.14(q,J＝7.3Hz,4H),0.79(t,J＝7.4Hz,6H).
13C NMR(100MHz,CDCl3)δ148.61,142.52,138.91,130.53,121.29,28.59,13.22.
19F NMR(376MHz,CDCl3)δ-80.63(t,J＝9.7Hz,3F),-108.52–-109.80(m,2F),-120.57–-121.38(m,2F),-125.52–-126.23(m,2F).
HRMS(ESI):m/z calculated for C26H19F18O6S2 +[M+H]+:833.0330,found:833.0320.
5.21g,97％收率,白色固体,m.p.85.0–87.5℃,洗脱试剂:正己烷.
1H NMR(400MHz,CDCl3)δ7.60(d,J＝8.7Hz,2H),7.46(d,J＝1.9Hz,2H),7.32(d,J＝8.7Hz,2H),7.21–7.11(m,2H),7.06(d,J＝16.3Hz,1H).
13C NMR(100MHz,CDCl3)δ150.19,149.95,141.36,136.12,131.69,128.82,126.91,122.13,119.38,114.13.
19F NMR(376MHz,CDCl3)δ-80.75(t,J＝9.7Hz,9F),-108.36(t,J＝13.3Hz,4F),-108.66–-109.05(m,2F),-120.28–-122.65(m,6F),-124.86–-126.69(m,6F).
HRMS(ESI):m/z calculated for C26H10F27O9S3 +[M+H]+:1074.9050,found:1074.9064.
2.60g,88％收率,无色油,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.37–7.10(m,4H),5.08(d,J＝7.7Hz,1H),4.56(dd,J＝13.3,6.3Hz,1H),4.14(q,J＝7.1Hz,2H),3.32–2.86(m,2H),1.40(s,9H),1.20(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.58,155.11,148.95,137.14,131.29,121.40,80.23,61.71,54.39,38.08,28.33,14.13.
19F NMR(376MHz,CDCl3)δ-80.72(t,J＝9.8Hz,3F),-109.04(t,J＝13.2Hz,2F),-120.88–-121.04(m,2F),-125.82–-126.02(m,2F).
HRMS(ESI):m/z calculated for C20H23F9NO7SNa+[M+Na]+:614.0865,found:614.0871.
2.84g,86％收率,白色固体,m.p.58.3–60.5℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.25–7.13(m,4H),6.70(d,J＝7.3Hz,1H),4.94(d,J＝5.5Hz,1H),4.81(dd,J＝13.3,6.3Hz,1H),4.37–3.97(m,3H),3.39–2.92(m,2H),1.43(s,9H),1.30(d,J＝7.0Hz,3H),1.20(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ172.53,171.02,155.59,148.93,136.84,131.33,121.46,80.39,61.90,53.14,50.27,37.50,28.36,18.12,14.14.
19F NMR(376MHz,CDCl3)δ-80.65(t,J＝9.6Hz,3F),-104.66–-113.56(m,2F),-120.75–-121.26(m,2F),-125.73–-126.05(m,2F).
HRMS(ESI):m/z calculated for C23H27F9N2O8SNa+[M+Na]+:685.1237,found:685.1241.
1.54g,73％收率,白色固体,m.p.111.6–115.2℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.22–7.08(m,4H),6.43(d,J＝6.7Hz,1H),4.95(d,J＝7.0Hz,1H),4.81(dd,J＝13.3,6.3Hz,1H),4.11(q,J＝7.1Hz,2H),3.94–3.69(m,1H),3.20–2.90(m,2H),2.04(dd,J＝12.9,6.4Hz,1H),1.41(s,9H),1.17(t,J＝7.1Hz,3H),0.89(d,J＝6.7Hz,3H),0.84(d,J＝5.6Hz,3H).
13C NMR(100MHz,CDCl3)δ171.60,171.03,155.94,148.96,136.82,131.30,121.50,80.14,61.88,60.25,53.11,37.59,30.78,28.37,19.32,17.92,14.11.
19F NMR(376MHz,CDCl3)δ-80.65(t,J＝9.7Hz,3F),-109.01(t,J＝13.3Hz,2F),-115.86–-123.49(m,2F),-123.78–-131.41(m,2F).
HRMS(ESI):m/z calculated for C25H32F9N2O8S+[M+H]+:691.1730,found:691,1736.
1.42g,64％收率,白色固体,m.p.116.0–120.7℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.35–7.09(m,9H),6.55(d,J＝7.4Hz,1H),5.04(d,J＝6.7Hz,1H),4.76(dd,J＝12.6,6.0Hz,1H),4.37(d,J＝6.3Hz,1H),4.22–3.96(m,2H),3.22–2.77(m,4H),1.42(s,9H),1.18(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.14,170.65,155.50,148.88,136.73,136.54,131.27,129.40,128.78,127.11,121.39,80.44,61.78,55.91,53.27,38.22,37.52,28.28,14.05.
19F NMR(376MHz,CDCl3)δ-80.70(t,J＝9.8Hz,3F),-108.29–-110.48(m,2F),-120.93(mm,J＝12.9,4.7Hz,2F),-125.54–-126.15(m,2F).
HRMS(ESI):m/z calculated for C29H32F9N2O8S+[M+H]+:739.1730,found:739.1742.
1.88g,75％收率,白色固体,m.p.120.5–123.1℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.29–7.12(m,9H),6.81(d,J＝7.8Hz,2H),5.13(d,J＝7.8Hz,1H),4.85–4.62(m,2H),4.17–4.01(m,2H),3.99–3.86(m,1H),3.14–2.90(m,4H),2.11(dq,J＝13.3,6.8Hz,1H),1.44(s,9H),1.15(t,J＝7.1Hz,3H),0.89(d,J＝6.8Hz,3H),0.82(d,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3)δ171.86,170.58,170.53,156.03,148.86,136.81,136.32,131.22,129.36,128.76,127.15,121.42,80.16,61.69,60.21,54.32,53.48,38.21,37.50,30.69,28.37,19.28,17.59,14.03.
19F NMR(376MHz,CDCl3)δ-80.70(t,J＝9.6Hz,3F),-109.10(t,J＝13.7Hz,2F),-120.78–-121.07(m,2F),-125.80–-126.15(m,2F).
HRMS(ESI):m/z calculated for C34H41F9N3O9S+[M+H]+:838.2414,found:838.2456.
1.92g,75％收率,白色固体,m.p.69.1–72.7℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.30–7.04(m,9H),6.73(d,J＝6.9Hz,1H),6.67(d,J＝7.3Hz,1H),5.34(d,J＝8.4Hz,1H),4.85–4.42(m,2H),4.14–3.98(m,2H),3.91(d,J＝8.4Hz,1H),3.12–2.89(m,4H),1.42(s,9H),1.13(t,J＝7.1Hz,3H),0.92(s,9H).
13C NMR(100MHz,CDCl3)δ171.11,170.64,170.56,155.89,148.81,136.80,136.25,131.21,129.37,128.66,127.06,121.35,79.73,62.46,61.63,54.44,53.40,38.45,37.54,34.54,28.39,26.60,13.97.
19F NMR(376MHz,CDCl3)δ-79.25–-83.30(m,3F),-109.17(t,J＝11.4Hz,2F),-119.73–-122.50(m,2F),-125.81–-126.16(m,2F).
HRMS(ESI):m/z calculated for C35H43F9N3O9S+[M+H]+:852.2571,found:852.2585.
2.08g,81％收率,白色固体,m.p.115.1–117.5℃,洗脱试剂:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.51(d,J＝6.4Hz,1H),7.24–7.13(m,5H),7.13–7.01(m,4H),6.94(d,J＝6.9Hz,1H),5.51(d,J＝7.2Hz,1H),5.42(d,J＝8.2Hz,1H),4.64(q,J＝6.4Hz,1H),4.32(d,J＝6.5Hz,1H),3.95(q,J＝7.1Hz,2H),3.02(d,J＝6.3Hz,2H),2.56–2.38(m,2H),2.08–1.92(m,4H),1.90–1.75(m,1H),1.31(s,9H),1.00(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.52,170.72,169.66,155.78,148.85,136.83,136.80,131.25,129.08,128.58,127.21,121.45,80.23,61.79,57.28,53.70,53.52,37.31,31.71,30.21,28.34,15.30,13.93.
19F NMR(376MHz,CDCl3)δ-80.69(t,J＝9.7Hz,3F),-109.00–-109.20(m,2F),-120.81–-121.10(m,2F),-125.77–-126.05(m,2F).
HRMS(ESI):m/z calculated for C33H39F9N3O9S2 +[M+H]+:856.1979,found:856.1993.
1.97g,68％收率,白色固体,m.p.149.1–153.2℃,洗脱试剂:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.61(s,1H),7.33(d,J＝13.5Hz,2H),7.24–7.06(m,9H),5.75(d,J＝6.7Hz,1H),4.94(d,J＝7.3Hz,1H),4.77(dd,J＝14.1,6.9Hz,1H),4.50(s,1H),4.39(d,J＝5.7Hz,1H),4.05(q,J＝7.0Hz,2H),3.16–2.91(m,4H),2.51(t,J＝7.0Hz,2H),2.16–1.82(m,6H),1.43(s,9H),1.11(t,J＝7.1Hz,3H),0.87(d,J＝6.6Hz,3H),0.82(d,J＝6.1Hz,3H).
13C NMR(100MHz,CDCl3)δ172.32,171.43,171.21,170.94,155.99,148.77,137.12,136.44,131.27,129.38,128.50,126.88,121.35,79.77,61.54,58.42,54.04,53.43,38.94,38.03,32.58,31.64,30.37,28.46,19.30,18.48,15.50,13.94.
19F NMR(376MHz,CDCl3)δ-80.73(t,J＝9.2Hz,3F),-109.16(t,J＝13.0Hz,2F),-120.83–-121.17(m,2F),-125.76–-126.25(m,2F).
HRMS(ESI):m/z calculated for C39H50F9N4O10S2 +[M+H]+:969.2819,found:969.2824.
1.74g,61％收率,白色固体,118.2–120.3℃,洗脱试剂:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.25–7.11(m,9H),7.01(d,J＝8.3Hz,1H),6.72(d,J＝6.8Hz,1H),5.26(d,J＝6.6Hz,1H),4.94(dd,J＝14.1,7.7Hz,1H),4.77(q,J＝6.9Hz,1H),4.26(t,J＝6.2Hz,1H),4.16–4.03(m,2H),3.80(d,J＝7.0Hz,1H),3.22–2.98(m,3H),2.98–2.84(m,1H),2.18–2.07(m,1H),1.41(s,9H),1.15(t,J＝7.2Hz,3H),0.97(s,9H),0.87(d,J＝6.7Hz,3H),0.77(d,J＝6.5Hz,3H).
13C NMR(100MHz,CDCl3)δ171.60,170.97,170.86,170.78,156.37,148.76,137.36,136.67,131.29,129.05,128.63,126.93,121.35,80.43,63.51,61.73,59.03,53.80,53.42,38.01,37.42,34.02,30.51,28.38,26.89,19.47,17.70,14.09.
19F NMR(376MHz,CDCl3)δ-80.63(t,J＝9.6Hz,3F),-109.11(t,J＝13.7Hz,2F),-120.87–-121.01(m,2F),-125.78–-125.98(m,2F).
HRMS(ESI):m/z calculated for C40H52F9N4O10S+[M+H]+:951.3255,found:951.3270.
实施例7
按照表6改变锌盐1、反应底物4、投料比、反应条件、洗脱液(洗脱液的选择详见表征部分)等条件中的至少一个，其他同实施例1，得到目标产物3或5，反应收率见表6。
表6
白色固体，熔点89.3–91.2℃,洗脱液:正己烷/EtOAc＝30/1.
1H NMR(400MHz,CDCl3)δ7.92(dd,J＝7.6,1.6Hz,1H),7.67-7.55(m,2H),7.34(d,J＝7.2Hz,1H),2.57(s,3H).
13C NMR(100MHz,CDCl3)δ199.47,143.85(dm,JC-F＝246.1Hz),140.64(dm,JC-F＝254.0Hz),138.22,137.72(dm,JC-F＝252.8Hz),132.59,132.22,129.81,129.73,125.41,115.94(td,JC-F＝18.9,4.1Hz),28.23.
19F NMR(376MHz,CDCl3)δ-142.33(dd,J＝23.1,7.8Hz,2F),-156.02(t,J＝20.8Hz,1F),-162.81(dt,J＝22.8,7.9Hz,2F).
HRMS(ESI):m/z calculated for C14H8F5O+[M+H]+:287.0490,found:287.0474.
白色固体，熔点74.6–76.8℃,洗脱液:正己烷/EtOAc＝30/1.
1H NMR(400MHz,CDCl3)δ10.08(s,1H),8.00(d,J＝8.0Hz,2H),7.61(d,J＝7.9Hz,2H).
13C NMR(100MHz,CDCl3)δ191.59,144.21(dm,JC-F＝249.2Hz),141.13(dm,JC-F＝255.5Hz),138.08(dm,JC-F＝253.7Hz),136.74,132.51,131.06,129.95,114.85(td,JC-F＝16.9,4.2Hz).
19F NMR(376MHz,CDCl3)δ-142.71(dd,J＝22.5,8.4Hz,2F),-153.61(t,J＝21.0Hz,1F),-161.38(td,J＝22.3,7.8Hz,2F).
HRMS(ESI):m/z calculated for C13H6F5O+[M+H]+:273.0333,found:273.0344.
白色固体，熔点159.5–163.1℃,洗脱液:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.56(dd,J＝6.5,2.9Hz,2H),7.52(d,J＝8.2Hz,2H),7.38–7.32(m,3H),7.24–7.14(m,5H),5.32(s,1H),3.77(s,3H),2.38(s,3H).
13C NMR(100MHz,CDCl3)δ157.17,144.87,144.48(dm,JC-F＝249.3Hz),140.76(dm,JC-F＝254.1Hz),137.69(dm,JC-F＝248.5Hz),136.43,135.20,132.84,131.91,130.05,129.46,129.19,128.97,128.93,122.40,115.73,113.10,112.18(td,J＝19.0,3.9Hz),76.45,55.86,21.71.
19F NMR(376MHz,CDCl3)δ-139.95(ddd,J＝32.0,23.4,8.1Hz,2F),-155.61(t,J＝20.9Hz,1F),-162.79–-163.04(m,2F).
HRMS(ESI):m/z calculated for C27H20F5O3S+[M+H]+:519.1048,found:519.1048.
白色固体，熔点219.9–222.0℃,洗脱液:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.76(d,J＝9.6Hz,1H),7.62(d,J＝8.0Hz,1H),7.42(s,1H),7.35(d,J＝7.9Hz,1H),6.52(d,J＝9.6Hz,1H).
13C NMR(100MHz,CDCl3)δ160.21,154.04,144.22(dm,JC-F＝249.6Hz),142.79,141.03(dm,JC-F＝256.8Hz),138.08(dm,JC-F＝254.8Hz),130.03,128.24,126.32,119.54,118.86,118.16,114.36(td,J＝16.6,4.1Hz).
19F NMR(376MHz,CDCl3)δ-142.61(dd,J＝22.6,7.9Hz,2F),-153.25(t,J＝21.0Hz,1F),-161.07(td,J＝22.0,7.8Hz,2F).
HRMS(ESI):m/z calculated for C15H6F5O2 +[M+H]+:313.0282,found:313.0287.
白色固体，熔点68.5–71.0℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.99–7.90(m,4H),7.71–7.61(m,2H).
13C NMR(100MHz,CDCl3)δ144.82(dm,JC-F＝249.5Hz),144.73,141.87(dm,JC-F＝256.9Hz),137.98(dm,JC-F＝254.8Hz),133.90,133.41,132.11,128.87,128.33,128.23,128.19,120.45,118.37,110.55(td,J＝18.4,3.9Hz).
19F NMR(376MHz,CDCl3)δ-80.80(t,J＝9.7Hz,3F),-109.75(t,J＝13.8Hz,2F),-120.58–-121.99(m,2F),-124.85–-127.23(m,2F),-139.70(dd,J＝22.3,7.8Hz,2F),-152.57(t,J＝20.7Hz,1F),-161.63(td,J＝21.4,6.9Hz,2F).
HRMS(ESI):m/z calculated for C20H7F14O3S+[M+H]+:592.9887,found:592.9883.
白色固体，熔点113.7–116.2℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.16–7.78(m,4H),7.78–7.39(m,2H).
13C NMR(100MHz,CDCl3)δ144.42(dm,JC-F＝249.1Hz),142.57–139.62(m,JC-F＝256.0Hz),137.60(dm,JC-F＝253.9Hz),133.26,131.93,128.24,128.20,124.09,114.45(td,J＝19.4,3.1Hz).
19F NMR(376MHz,CDCl3)δ-140.97(d,J＝24.0Hz,4F),-153.37(t,J＝21.0Hz,2F),-161.28(td,J＝22.4,7.0Hz,4F).
HRMS(ESI):m/z calculated for C22H7F10 +[M+H]+:461.0383,found:461.0392.
白色固体，熔点125.7–128.1℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ8.06(dd,J＝4.8,3.3Hz,2H),7.72-7.60(m,2H),7.59-7.50(m,2H).
13C NMR(100MHz,CDCl3)δ144.76(dm,JC-F＝248.7Hz),144.51(dm,JC-F＝249.5Hz),141.28(dm,JC-F＝255.5Hz),140.83(dm,JC-F＝255.6Hz),138.12(dm,JC-F＝253.9Hz),137.99(dm,JC-F＝254.3Hz),133.56,131.60,130.95,130.70,130.44,128.40,126.31,125.41,124.69,124.09,115.55(td,JC-F＝16.9,4.0Hz),114.03(td,JC-F＝19.3,3.7Hz).
19F NMR(376MHz,CDCl3)δ-139.30(dd,J＝22.6,8.5Hz,2F),-142.96(dd,J＝23.0,8.2Hz,2F),-154.05(t,J＝20.8Hz,1F),-154.80(t,J＝21.0Hz,1F),-161.36–-161.66(m,2F),-161.84(td,J＝22.5,8.0Hz,2F).
HRMS(ESI):m/z calculated for C22H7F10 +[M+H]+:461.0383,found:461.0376
白色固体，熔点89.3–92.4℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.83(d,J＝7.5Hz,2H),7.50(d,J＝7.6Hz,2H),7.43(t,J＝7.4Hz,2H),7.40–7.30(m,10H).
13C NMR(100MHz,CDCl3)δ150.36,146.97,144.27(dm,JC-F＝248.2Hz),140.39,140.47(dm,JC-F＝248.8Hz),137.97(dm,JC-F＝245.8Hz),130.30,128.61,128.16,128.11,126.37,125.09,120.58,115.62(td,JC-F＝17.2,4.2Hz),65.35.
19F NMR(376MHz,CDCl3)δ-143.12(dd,J＝22.6,8.2Hz,4F),-155.52(t,J＝21.0Hz,2F),-162.11(td,J＝22.7,22.2,8.4Hz,4F).
HRMS(ESI):m/z calculated for C37H17F10 +[M+H]+:651.1165,found:651.1156.
白色固体，熔点153.1–154.4℃,洗脱液:正己烷/EtOAc＝10/1.
1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.5Hz,4H),7.63(d,J＝8.3Hz,4H).
13C NMR(100MHz,CDCl3)δ144.22(d,JC-F＝249.3Hz),142.06,141.33(d,JC-F＝256.0Hz),138.11(d,JC-F＝253.8Hz),132.04,131.48,128.35,114.13(td,JC-F＝16.6,4.0Hz).
19F NMR(376MHz,CDCl3)δ-142.69(dd,J＝22.2,8.2Hz,4F),-152.91(t,J＝21.1Hz,2F),-161.01(td,J＝22.1,8.2Hz,4F).
HRMS(ESI):m/z calculated for C24H9F10O2S+[M+H]+:551.0158,found:551.0146.
白色固体，熔点229.2–233.7℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.63(s,3H).
13C NMR(100MHz,CDCl3)δ144.34(dm,JC-F＝250.4Hz),141.20(dm,JC-F＝256.8Hz),138.17(dm,JC-F＝254.6Hz),132.77,127.96,114.23(td,JC-F＝16.3,3.5Hz).
19F NMR(376MHz,CDCl3)δ-142.87(dd,J＝22.5,7.8Hz,6F),-153.32(t,J＝21.0Hz,3F),-161.06(td,J＝22.0,7.7Hz,6F).
HRMS(ESI):m/z calculated for C24H4F15 +[M+H]+:577.0068,found:577.0065.
白色固体，熔点203.8–204.7℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.43(d,J＝8.1Hz,6H),7.33(d,J＝8.2Hz,6H),5.73(s,1H).
13C NMR(100MHz,CDCl3)δ144.34(dm,JC-F＝248.6Hz),144.22,140.54(dm,JC-F＝253.3Hz),138.03(dm,JC-F＝252.1Hz),130.55,129.94,125.10,115.64(td,JC-F＝17.0,3.9Hz),56.44.
19F NMR(376MHz,CDCl3)δ-143.20(dd,J＝23.0,8.1Hz,6F),-155.43(t,J＝21.0Hz,3F),-162.10(td,J＝22.8,8.2Hz,6F).
HRMS(ESI):m/z calculated for C37H13F15Na+[M+Na]+:765.0670,found:765.0657.
白色固体，熔点265.5–207.8℃,洗脱液:正己烷.
1H NMR(400MHz,Chloroform-d)δ7.69–6.97(m,16H).
13C NMR(100MHz,CDCl3)δ144.31(dm,JC-F＝248.7Hz),143.78,141.41,140.51(dm,JC-F＝254.9Hz),137.99(dm,JC-F＝251.8Hz),131.75,129.96,125.34,115.64(td,JC-F＝17.0,3.8Hz).
19F NMR(376MHz,CDCl3)δ-143.10(dd,J＝23.3,8.1Hz,8F),-155.36(t,J＝20.8Hz,4F),-162.11(td,J＝22.6,8.2Hz,8F).
HRMS(ESI):m/z calculated for C50H17F20 +[M+H]+:997.1005,found:997.1000.
白色固体，熔点101.2–103.6℃,洗脱液:正己烷/EtOAc＝10/1.
1H NMR(400MHz,CDCl3)δ9.99(s,1H),8.59(s,1H),8.31(d,J＝8.0Hz,1H),7.50(d,J＝8.0Hz,1H),4.38(q,J＝7.1Hz,2H),2.81(s,3H),1.40(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ189.77,166.90,162.06,161.49,144.14(dm,JC-F＝249.4Hz),141.54(dm,JC-F＝256.9Hz),137.87(dm,JC-F＝254.7Hz),135.10,135.01,133.29,131.57,129.96,129.00,123.42,112.45(td,JC-F＝18.6,4.0Hz),61.70,17.64,14.44.
19F NMR(376MHz,CDCl3)δ-140.51(dd,J＝22.8,7.8Hz,2F),-152.76(t,J＝20.9Hz,1F),-161.20(dt,J＝22.2,7.7Hz,2F).
HRMS(ESI):m/z calculated for C20H13F5NO3S+[M+H]+:442.0531,found:442.0543.
白色固体，熔点114.4–116.2℃,洗脱液:正己烷/EtOAc＝16/1.
1H NMR(400MHz,CDCl3)δ8.40(d,J＝1.9Hz,1H),8.24(dd,J＝9.0,2.1Hz,1H),7.93(d,J＝8.1Hz,2H),7.67–7.52(m,3H),2.90(t,J＝7.7Hz,2H),1.85–1.70(m,2H),1.43–1.28(m,2H),0.89(t,J＝7.3Hz,3H).
13C NMR(100MHz,CDCl3)δ190.13,168.84,156.45,144.94,144.25(dm,JC-F＝245.9Hz),141.08(dm,JC-F＝256.6Hz),138.08(dm,JC-F＝254.6Hz),139.20,131.45,130.83,129.37,127.54,120.69,117.96,117.00,114.82(td,JC-F＝16.2,4.1Hz),111.67,30.05,28.33,22.48,13.71.
19F NMR(376MHz,CDCl3)δ-142.60(dd,J＝22.7,8.0Hz,2F),-153.62(t,J＝21.0Hz,1F),-161.30(dt,J＝22.3,8.0Hz,2F).
HRMS(ESI):m/z calculated for C25H17F5NO4 +[M+H]+:490.1072,found:490.1077.
白色固体，熔点170.6–172.9℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.58(d,J＝8.2Hz,2H),7.41(d,J＝8.1Hz,2H),7.25–7.15(m,2H),7.06–6.96(m,2H),6.91–6.78(m,2H),6.62–6.52(m,2H),5.34(dd,J＝10.3,2.7Hz,1H),5.08(brs,1H),4.78(d,J＝4.7Hz,1H),3.29–3.06(m,1H),2.24–1.94(m,3H),1.93–1.71(m,1H).
13C NMR(100MHz,CDCl3)δ172.74,162.76(d,JC-F＝247.3Hz),156.41(d,JC-F＝236.4Hz),144.28(dm,JC-F＝248.7Hz),143.27(d,JC-F＝1.7Hz),142.03,140.55(dm,JC-F＝252.4Hz),138.01(dm,JC-F＝255.4Hz),134.62(d,JC-F＝3.1Hz),130.60,127.92,127.79(d,JC-F＝8.4Hz),125.89,115.86(d,JC-F＝22.3Hz),115.72(d,JC-F＝21.7Hz),115.68(td,JC-F＝17.1,3.6Hz),115.28(d,JC-F＝7.4Hz),79.55,58.93,45.27,29.61,21.31.
19F NMR(376MHz,CDCl3)δ-107.25–-119.42(m,1F),-126.68(s,1F),-143.15(dd,J＝22.8,8.1Hz,2F),-155.25(t,J＝20.9Hz,1F),-162.00(td,J＝22.7,8.2Hz,2F).
HRMS(ESI):m/z calculated for C30H21F7NO2 +[M+H]+:560.1455,found:560.1462.
白色固体，熔点148.9–150.6℃,洗脱液:正己烷/EtOAc＝10/1.
1H NMR(400MHz,CDCl3)δ7.42(d,J＝8.1Hz,1H),7.21(d,J＝8.0Hz,1H),7.17(s,1H),2.98(dd,J＝9.1,4.2Hz,2H),2.62-2.43(m,2H),2.37(td,J＝10.8,4.2Hz,1H),2.23-1.94(m,4H),1.76-1.43(m,6H),0.94(s,3H).
13C NMR(100MHz,CDCl3)δ220.64,144.25(dm,JC-F＝248.0Hz),141.28,140.32(dm,JC-F＝253.3Hz),137.90(dm,JC-F＝251.4Hz),137.18,130.67,127.48,125.84,123.84,115.97(td,JC-F＝17.5,3.9Hz),50.61,48.01,44.52,38.01,35.89,31.67,29.41,26.44,25.66,21.66,13.89.
19F NMR(376MHz,CDCl3)δ-143.18(dd,J＝22.7,8.3Hz,2F),-156.09(t,J＝21.2Hz,1F),-162.43(td,J＝22.5,8.1Hz,2F).
HRMS(ESI):m/z calculated for C24H22F5O+[M+H]+:421.1585,found:421.1590.
白色固体，熔点257.6–260.7℃,洗脱液:正己烷/EtOAc＝1/1.
1H NMR(400MHz,DMSO-d6)δ8.76(s,1H),8.31(s,1H),8.27(d,J＝8.8Hz,1H),7.91(d,J＝8.6Hz,1H),7.37(s,1H),6.56(s,1H),5.42(s,2H),5.29(s,2H),1.92-1.81(m,2H),0.88(t,J＝7.3Hz,3H).
13C NMR(100MHz,DMSO-d6)δ172.46,156.77,153.81,149.98,147.68,145.16,143.83(dm,JC-F＝246.9Hz),140.14(dm,JC-F＝253.3Hz),137.39(dm,JC-F＝249.9Hz),131.97,131.39,130.65,129.61,127.63,124.78,119.51,114.66(td,J＝17.4,3.4Hz),97.15,72.40,65.27,50.28,30.34,7.78.
19F NMR(376MHz,DMSO-d6)δ-143.18(dd,J＝25.0,7.5Hz,2F),-155.12(t,J＝22.2Hz,1F),-162.33(td,J＝23.6,7.2Hz,2F).
HRMS(ESI):m/z calculated for C26H16F5N2O4 +[M+H]+:515.1025,found:515.1030.
白色固体，熔点157.8–159.7℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.47(d,J＝8.0Hz,4H),7.38(d,J＝8.2Hz,4H),2.25(q,J＝7.3Hz,4H),0.87(t,J＝7.4Hz,6H).
13C NMR(100MHz,CDCl3)δ144.36(dm,JC-F＝248.8Hz),143.67,140.52(dm,JC-F＝237.3Hz),139.34,137.98(dm,JC-F＝237.8Hz),130.06,129.20,124.60,116.02(td,JC-F＝16.9,4.0Hz),28.66,13.51.
19F NMR(376MHz,CDCl3)δ-143.22(dd,J＝22.9,7.8Hz,4F),-155.87(td,J＝21.1,11.3Hz,2F),-162.37(td,J＝22.1,8.8Hz,4F).
HRMS(ESI):m/z calculated for C20H9F10O2S+[M+H]+:569.1322,found:569.1298
白色固体，熔点184.7–187.2℃,洗脱液:正己烷.
1H NMR(400MHz,CDCl3)δ7.73–7.60(m,4H),7.46(d,J＝8.0Hz,2H),7.41(s,1H),7.31–7.17(m,2H).
13C NMR(100MHz,CDCl3)δ145.84–145.36(m),143.39–142.88(m),142.52–141.59(m),140.02–139.03(m),138.55,137.71,137.13–136.56(m),131.13),130.76,130.15,129.20,128.42,127.77,127.10,126.22,115.60(td,J＝16.8,3.8Hz),114.96(td,J＝16.9,3.9Hz).
19F NMR(376MHz,CDCl3)δ-142.71(dd,J＝22.8,8.1Hz,4F),-143.14(dd,J＝23.0,8.1Hz,2F),-154.12(t,J＝21.0Hz,2F),-155.23(t,J＝21.0Hz,1F),-161.45(td,J＝22.5,8.1Hz,4F),-162.01(td,J＝22.7,8.1Hz,2F).
HRMS(ESI):m/z calculated for C32H10F15 +[M+H]+:679.0537,found:679.0541
白色固体，熔点76.1–78.1℃,洗脱液:正己烷/EtOAc＝5/1.
1H NMR(400MHz,CDCl3)δ7.35(d,J＝7.8Hz,2H),7.28(d,J＝8.0Hz,2H),5.07(d,J＝8.4Hz,1H),4.61(d,J＝7.3Hz,1H),4.17(q,J＝7.1Hz,2H),3.29–2.91(m,2H),1.42(s,9H),1.22(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.85,155.19,144.27(dm,JC-F＝248.9Hz),140.47(dm,JC-F＝254.4Hz),137.97(dm,JC-F＝252.3Hz),137.83,130.35,129.93,125.15,115.76(td,JC-F＝17.9,3.9Hz),80.16,61.63,54.48,38.58,28.40,14.19.
19F NMR(376MHz,CDCl3)δ-143.23(dd,J＝23.3,8.2Hz,2F),-155.62(t,J＝20.8Hz,1F),-162.24(td,J＝22.2,8.2Hz,2F).
HRMS(ESI):m/z calculated for C22H23F5NO4 +[M+H]+:460.1542,found:460.1548.
白色固体，熔点74.3–73.8℃,洗脱液:正己烷/EtOAc＝5/1.
1H NMR(400MHz,CDCl3)δ7.33(d,J＝7.7Hz,2H),7.26(d,J＝7.9Hz,2H),6.70(d,J＝7.4Hz,1H),4.98(s,1H),4.86(dd,J＝13.2,6.4Hz,1H),4.23–4.01(m,3H),3.31–3.07(m,2H),1.42(s,9H),1.31(d,J＝6.8Hz,3H),1.20(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ172.49,171.25,155.54,144.20(dm,JC-F＝248.4Hz),140.44(dm,JC-F＝258.1Hz),137.92(dm,JC-F＝253.1Hz),137.51,130.33,129.89,125.21,115.65(dm,JC-F＝16.9,3.8Hz),80.29,61.79,53.20,50.26,37.98,28.36,18.33,14.14.
19F NMR(376MHz,CDCl3)δ-143.22(dd,J＝23.0,7.8Hz,2F),-155.50(t,J＝20.9Hz,1F),-162.17(td,J＝22.3,8.0Hz,2F).
HRMS(ESI):m/z calculated for C25H27F5NO5Na+[M+Na]+:553.1732,found:553.1734.
白色固体，熔点153.4–155.6℃,洗脱液:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.26(d,J＝8.2Hz,2H),7.21(d,J＝8.0Hz,2H),6.52(d,J＝7.9Hz,1H),5.02(d,J＝8.8Hz,1H),4.82(q,J＝6.7Hz,1H),4.08(q,J＝7.2Hz,2H),3.86(d,J＝7.9Hz,1H),3.10(d,J＝3.9Hz,2H),2.03(dq,J＝13.6,6.4Hz,1H),1.36(s,9H),1.13(t,J＝7.2Hz,3H),0.86(d,J＝6.8Hz,3H),0.80(d,J＝6.7Hz,3H).
13C NMR(100MHz,CDCl3)δ171.52,171.27,155.91,144.20(dm,JC-F＝247.6Hz),140.43(dm,JC-F＝254.0Hz),137.92(dm,JC-F＝251.6Hz),137.53,130.36,129.84,125.22,115.68(td,JC-F＝17.1,4.1Hz),79.98,61.72,60.11,53.16,38.06,30.91,28.34,19.26,17.81,14.06.
19F NMR(376MHz,CDCl3)δ-143.20(dd,J＝23.1,8.4Hz,2F),-155.64(t,J＝20.8Hz,1F),-162.29(td,J＝22.3,8.2Hz,2F).
HRMS(ESI):m/z calculated for C27H32F5N2O5 +[M+H]+:559.2226,found:559.2234.
白色固体，熔点136.9–138.3℃,洗脱液:正己烷/EtOAc＝4/1.
1H NMR(400MHz,CDCl3)δ7.36–7.27(m,4H),7.27–7.14(m,5H),6.50(d,J＝7.6Hz,1H),5.09–4.98(m,1H),4.82(q,J＝6.6Hz,1H),4.39(d,J＝7.4Hz,1H),4.21–4.05(m,2H),3.13(d,J＝6.2Hz,2H),3.07(d,J＝6.8Hz,2H),1.42(s,9H),1.19(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.03,170.89,155.46,144.19(dm,JC-F＝248.6Hz),140.42(dm,JC-F＝254.5Hz),139.17,137.88(dm,JC-F＝255.3Hz),137.41,136.58,130.28,129.83,129.45,128.77,127.09,125.17,115.64(dm,JC-F＝17.2,3.9Hz),80.37,61.70,55.85,53.33,38.34,38.03,28.30,14.08.
19F NMR(376MHz,CDCl3)δ-143.18(dd,J＝23.3,8.2Hz,2F),-155.53(t,J＝20.9Hz,1F),-162.20(td,J＝21.9,8.0Hz,2F).
HRMS(ESI):m/z calculated for C31H32F5N2O5 +[M+H]+:607.2226,found:607.2239.
白色固体，熔点157.5–159.1℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.32–7.24(m,4H),7.24–7.17(m,3H),7.14(d,J＝8.2Hz,2H),6.61(d,J＝7.5Hz,1H),6.48(d,J＝6.6Hz,1H),4.96(d,J＝7.8Hz,1H),4.79–4.60(m,2H),4.17–4.02(m,2H),3.97–3.82(m,1H),3.15–2.94(m,4H),2.11(dq,J＝13.4,6.7Hz,1H),1.42(s,9H),1.16(t,J＝7.1Hz,3H),0.88(d,J＝6.8Hz,3H),0.79(d,J＝6.7Hz,3H).
13C NMR(100MHz,CDCl3)δ171.70,170.69,170.39,155.99,144.18(dm,JC-F＝252.2Hz),140.40(dm,JC-F＝254.7Hz),137.89(dm,JC-F＝252.7Hz),137.39,136.34,130.31,129.76,129.42,128.79,127.19,125.16,115.63(dm,JC-F＝17.6,3.8Hz),80.17,61.65,60.16,54.30,53.50,38.26,37.92,30.72,28.38,19.29,17.56,14.07.
19F NMR(376MHz,CDCl3)δ-143.19(dd,J＝23.0,8.0Hz,2F),-155.54(t,J＝21.0Hz,1F),-162.19(td,J＝22.3,7.8Hz,2F).
HRMS(ESI):m/z calculated for C36H41F5N3O6 +[M+H]+:706.2910,found:706.2917.
白色固体，熔点96.5–99.8℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.33–7.24(m,4H),7.23–7.17(m,3H),7.13(d,J＝8.1Hz,2H),6.55(d,J＝7.8Hz,1H),6.41(d,J＝7.4Hz,1H),5.25(d,J＝8.9Hz,1H),4.84–4.55(m,2H),4.23–3.96(m,2H),3.86(d,J＝8.8Hz,1H),3.18–2.83(m,4H),1.43(s,9H),1.16(t,J＝7.1Hz,3H),0.93(s,9H).
13C NMR(100MHz,CDCl3)δ171.00,170.66,170.32,155.87,144.15(dm,JC-F＝248.0Hz),140.49(dm,JC-F＝242.3Hz),137.92(dm,JC-F＝252.5Hz),137.30,136.28,130.31,129.78,129.46,128.79,127.21,125.20,115.61(dm,JC-F＝17.2,3.8Hz),79.93,62.66,61.69,54.40,53.45,38.37,37.89,34.49,28.42,26.60,14.08.
19F NMR(376MHz,CDCl3)δ-143.19(dd,J＝23.0,8.0Hz,2F),-155.51(t,J＝21.0Hz,1F),-162.18(td,J＝22.5,8.0Hz,2F).
HRMS(ESI):m/z calculated for C37H43F5N3O6 +[M+H]+:720.3067,found:720.3076.
白色固体，熔点190.3–193.1℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.44(d,J＝6.0Hz,1H),7.36–7.27(m,7H),7.22(d,J＝8.1Hz,2H),6.50(d,J＝6.9Hz,1H),5.45(d,J＝6.8Hz,1H),5.27(d,J＝7.5Hz,1H),4.85–4.69(m,1H),4.35(d,J＝6.3Hz,1H),4.07(q,J＝7.0Hz,2H),3.27–3.06(m,2H),2.63–2.45(m,2H),2.08(s,3H),2.00–1.80(m,2H),1.40(s,9H),1.13(t,J＝7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.19,170.78,169.37,155.70,144.23(dm,JC-F＝248.4Hz),140.57(dm,JC-F＝240.0Hz),137.97(dm,JC-F＝253.0Hz),137.33,136.95,130.43,129.83,129.21,128.74,127.39,125.32,115.65(td,J＝17.0,3.9Hz),80.35,61.82,57.62,53.64,53.53,37.72,31.60,30.27,28.38,15.36,14.05.
19F NMR(376MHz,CDCl3)δ-143.18(dd,J＝23.1,7.9Hz,2F),-155.42(t,J＝21.0Hz,1F),-162.09(td,J＝22.4,7.9Hz,2F).
HRMS(ESI):m/z calculated for C35H38F5N3O6SNa+[M+Na]+:746.2294,found:746.2303.
白色固体，熔点196.8–199.1℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.33(d,J＝7.1Hz,1H),7.29(d,J＝8.0Hz,2H),7.25–7.11(m,8H),7.07(d,J＝4.2Hz,1H),5.62(d,J＝7.4Hz,1H),4.90(q,J＝7.4Hz,1H),4.80(q,J＝6.8Hz,1H),4.44(t,J＝7.0Hz,1H),4.34(d,J＝6.4Hz,1H),4.07(q,J＝7.1Hz,2H),3.18–3.04(m,3H),3.04–2.93(m,1H),2.52(t,J＝7.2Hz,2H),2.15–1.87(m,6H),1.42(s,9H),1.13(t,J＝7.1Hz,3H),0.87(d,J＝6.7Hz,3H),0.81(d,J＝6.4Hz,3H).
13C NMR(100MHz,CDCl3)δ172.20,171.05,170.94,170.76,156.01,144.19(dm,JC-F＝248.5Hz),140.42(dm,JC-F＝254.5Hz),137.84(dm,JC-F＝251.3Hz),137.73,136.58,130.28,129.81,129.31,128.66,127.01,125.05,115.68(td,J＝17.0,3.9Hz),80.30,61.58,58.72,54.20,54.13,53.51,38.44,38.12,31.62,30.99,30.42,28.44,19.30,17.91,15.50,14.06.
19F NMR(376MHz,CDCl3)δ-143.27(dd,J＝23.1,8.1Hz,2F),-155.56(t,J＝21.0Hz,1F),-162.21(td,J＝22.5,8.0Hz,2F).
HRMS(ESI):m/z calculated for C41H50F5N4O7S+[M+H]+:837.3315,found:837.3330.
白色固体，熔点135.2–138.6℃,洗脱液:正己烷/EtOAc＝3/1.
1H NMR(400MHz,CDCl3)δ7.38–7.05(m,11H),7.00(d,J＝6.5Hz,1H),5.43(d,J＝7.3Hz,1H),5.12–4.97(m,1H),4.87(dd,J＝13.7,6.7Hz,1H),4.39(t,J＝6.5Hz,1H),4.11(dd,J＝13.6,6.7Hz,2H),3.96(d,J＝7.7Hz,1H),3.27–2.92(m,4H),2.16–2.01(m,1H),1.44(s,9H),1.15(t,J＝7.1Hz,3H),0.98(s,9H),0.89(d,J＝6.5Hz,3H),0.82(d,J＝6.1Hz,3H).
13C NMR(100MHz,CDCl3)δ171.38,171.03,170.95,170.67,156.09,137.82,136.48,130.14,129.69,129.12,128.52,126.84,124.86,115.58(td,JC-F＝17.2,4.2Hz),79.86,62.85,61.52,58.62,53.70,53.36,38.38,37.97,34.23,30.93,28.33,26.78,19.29,17.94,13.96.
19F NMR(376MHz,CDCl3)δ-143.30(dd,J＝23.1,7.9Hz,2F),-155.53(t,J＝21.0Hz,1F),-162.16(td,J＝22.3,7.8Hz,2F).
HRMS(ESI):m/z calculated for C42H51F5N4O7 +[M+H]+:819.3751,found:819.3765.
对比例5
在配备磁性搅拌棒的10mL Schlenk管中加入五氟苯甲酸锌1a(487.5mg，1.0mmol)、三氟酸盐4k’(212.2mg，0.5mmol)和Pd(PPh3)4(28.9mg，0.025mmol)。反应容器被排空，并充满氩气三次。然后，在氩气下，用注射器加入DMF(2.0mL)。在60℃或90℃搅拌反应混合物12h。反应完成后，加入饱和氯化铵水溶液(20mL)淬灭，用乙酸乙酯(3×10mL)萃取。分离有机层后用硫酸钠干燥，过滤，真空蒸发。粗产物经硅胶柱层析纯化，得到纯目标化合物。结果显示，当反应温度为60℃时，产物5e收率64％，5f收率7％；当反应温度为90℃时，产物5e收率为0％，5f收率为69％。
对比例6
在配备磁性搅拌棒的10mL Schlenk管中加入五氟苯甲酸锌1a(487.5mg，1.0mmol)、三氟酸盐4z’(220.7mg，0.5mmol)和Pd(PPh3)4(28.9mg，0.025mmol)。反应容器被排空，并充满氩气三次。然后，在氩气下，用注射器加入DMF(2.0mL)。搅拌反应混合物12h。反应完成后，加入饱和氯化铵水溶液(20mL)淬灭，用乙酸乙酯(3×10mL)萃取。分离有机层后用硫酸钠干燥，过滤，真空蒸发。粗产物经硅胶柱层析纯化，产物为5t，收率为46％。
Claims (8)
1.一种多氟芳基或杂芳基衍生物的制备方法，其特征在于：所述制备方法包括：在反应容器中加入式1所示的多氟苯甲酸锌盐、化合物2、催化剂和有机溶剂，所述催化剂为Pd(PPh3)4、Pd(OAc)2/PPh3或Pd(TFA)2/PPh3，于60-100℃下经过脱羧和交叉偶联得到式3所示的多氟芳基或杂芳基衍生物；
式1中，n为自然数，取值范围为2-5，R1为H、C1-C4的烷氧基、-COOR2、硝基或苯基，其中R2为C1-C4的烷基；并且，当n＝2时，R1不为H；
式2中，Ar为芳基或杂芳基，所述的芳基或杂芳基未被取代或者被取代；X为Br或ONf；m为自然数，m≥1；
式3中，当m＝1时，x＝1；当m≥2时，x≥1。
2.如权利要求1所述的制备方法，其特征在于：n为2、3或4时，R1为C1-C4的烷氧基、-COOR2、硝酸或苯基。
3.如权利要求1所述的制备方法，其特征在于：
所述的芳基是苯基或多环芳基，所述的多环芳基是非稠合多环芳基或稠合多环芳基；
所述的杂芳基是五元或六元的单杂芳基、非稠合多环杂芳基或稠合杂芳基，所述的非稠合多环杂芳基为杂环和杂环连接形成的基团或者苯环和杂环连接形成的基团，所述稠合杂芳基为苯环与杂环稠合的苯稠杂环基或者杂环与杂环稠合的稠杂环基；
所述的芳基和杂芳基上除了取代基X外，不含其他取代基，或者含有至少一个其他取代基，所述的取代基是氰基、硝基、C1-C10烷基、C1-C10烷氧基、C1-C10烷硫基、-COR3、-COOR4、-SO2R5、取代烷基、取代烯基或羟基；其中R3选择H、C1-C10烷基或(X)m-Ar’-；R4选择C1-C10烷基；R5选择(X)m-Ar’-；所述的取代烷基是指C1-C10烷基中的至少一个H被取代，取代基各自独立选自-COOR6、苯基、对甲苯磺酰基、酰胺基或BocNH-，其中R6选择C1-C10烷基；所述取代烯基是指C2-C10烯基中的至少一个烯基H被取代基取代，所述取代基为(X)m-Ar’-；所述Ar’是Ar-(X)m中的Ar去掉一个H形成的基团。
4.如权利要求1所述的制备方法，其特征在于：所述的有机溶剂是DMF、乙腈、DMA、NMP、THF、二氧六环中的至少一种。
5.如权利要求1所述的制备方法，其特征在于：所述化合物2与催化剂的投料摩尔比为1：0.005-0.20。
6.如权利要求1所述的制备方法，其特征在于：所述化合物2与催化剂的投料摩尔比为1：0.05。
7.如权利要求1所述的制备方法，其特征在于：若要实现化合物2中所有X取代基均发生反应，则使式1所示的多氟苯甲酸锌盐和化合物2的投料摩尔比保持在m以上。
8.如权利要求7所述的制备方法，其特征在于：控制式1所示的多氟苯甲酸锌盐和化合物2的投料摩尔比为m，反应温度为60℃。
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