WO2023240791A1 - 一种绿色的n-甲基酰胺化合物的制备方法 - Google Patents
一种绿色的n-甲基酰胺化合物的制备方法 Download PDFInfo
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- WO2023240791A1 WO2023240791A1 PCT/CN2022/113978 CN2022113978W WO2023240791A1 WO 2023240791 A1 WO2023240791 A1 WO 2023240791A1 CN 2022113978 W CN2022113978 W CN 2022113978W WO 2023240791 A1 WO2023240791 A1 WO 2023240791A1
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- Prior art keywords
- methylamide
- mmol
- green
- reaction
- mhz
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- -1 n-methylamide compound Chemical class 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 56
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 52
- 239000002904 solvent Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000000654 additive Substances 0.000 claims abstract description 7
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 7
- 230000000996 additive effect Effects 0.000 claims abstract description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 146
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 72
- 150000001408 amides Chemical class 0.000 claims description 52
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical class NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 claims 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 claims 1
- 229960003750 ethyl chloride Drugs 0.000 claims 1
- 229910001507 metal halide Inorganic materials 0.000 claims 1
- 150000005309 metal halides Chemical group 0.000 claims 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 abstract description 29
- 239000000758 substrate Substances 0.000 abstract description 14
- 239000003054 catalyst Substances 0.000 abstract description 11
- 150000003511 tertiary amides Chemical class 0.000 abstract description 11
- 150000008430 aromatic amides Chemical class 0.000 abstract description 4
- 150000008431 aliphatic amides Chemical class 0.000 abstract description 2
- 238000004458 analytical method Methods 0.000 description 44
- 238000012360 testing method Methods 0.000 description 44
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 23
- 238000001179 sorption measurement Methods 0.000 description 23
- 239000012298 atmosphere Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 238000006552 photochemical reaction Methods 0.000 description 10
- 239000007800 oxidant agent Substances 0.000 description 9
- 230000001590 oxidative effect Effects 0.000 description 5
- 230000004913 activation Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000017858 demethylation Effects 0.000 description 3
- 238000010520 demethylation reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 102000012440 Acetylcholinesterase Human genes 0.000 description 2
- 108010022752 Acetylcholinesterase Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229940022698 acetylcholinesterase Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 description 2
- 229960004671 enzalutamide Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- JLNGEXDJAQASHD-UHFFFAOYSA-N N,N-Diethylbenzamide Chemical compound CCN(CC)C(=O)C1=CC=CC=C1 JLNGEXDJAQASHD-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000003749 cleanliness Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZKXWKVVCCTZOLD-UHFFFAOYSA-N copper;4-hydroxypent-3-en-2-one Chemical compound [Cu].CC(O)=CC(C)=O.CC(O)=CC(C)=O ZKXWKVVCCTZOLD-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 230000006204 deethylation Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 150000004698 iron complex Chemical class 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- LTVDDOQQWIPTLL-UHFFFAOYSA-K iron(3+) 5,10,15,20-tetraphenyl-21,23-dihydroporphyrin trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Fe+3].c1cc2nc1c(-c1ccccc1)c1ccc([nH]1)c(-c1ccccc1)c1ccc(n1)c(-c1ccccc1)c1ccc([nH]1)c2-c1ccccc1 LTVDDOQQWIPTLL-UHFFFAOYSA-K 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 229960002516 physostigmine salicylate Drugs 0.000 description 1
- HZOTZTANVBDFOF-PBCQUBLHSA-N physostigmine salicylate Chemical compound OC(=O)C1=CC=CC=C1O.C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C HZOTZTANVBDFOF-PBCQUBLHSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 210000005267 prostate cell Anatomy 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/07—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/58—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/59—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
- C07C235/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/60—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- 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
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile 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
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
Definitions
- the invention relates to a preparation method of green visible light-catalyzed N -methylamide compounds, and belongs to the technical field of organic synthesis.
- N -methylamide compounds are an important class of structural skeletons that are commonly used in the fields of medicine, agricultural chemicals, polymers, functional organic materials, natural products and other fields.
- Many drug molecules contain N -methylamide skeletons, such as axitinib: a small molecule tyrosine kinase inhibitor that can inhibit multiple targets, including VEGFR-1, VEGFR-2, VEGFR- 3. Platelet-derived growth factor receptor (PDGFR) and cKIT (CD117);
- Physostigmine salicylate a reversible acetylcholinesterase (AChE) inhibitor that can penetrate the blood-brain barrier and stimulate the central nervous system Cholinergic neurotransmission and can reverse memory deficits in Alzheimer's disease transgenic mice.
- this drug molecule is also an antidote for anticholinergic toxicity; Enzalutamide: an androgenic Hormone receptor (androgen receptor (AR)) antagonist.
- the IC50 value for inhibiting AR in LNCaP prostate cells is 36 nM.
- Enzalutamide is an activator of autophagy. Therefore, the synthesis of N -methylamide compounds is particularly important. Demethylation of tertiary amides is an important method for constructing N -methylamides. Through a literature survey, it was found that this type of method has some obvious shortcomings, such as harsh reaction conditions, low yield, narrow substrate range, high reaction temperature, use of relatively expensive metal catalysts, the need for excess oxidants, and a single reaction mode ( Mostly thermal reactions) etc.
- the purpose of the present invention is to provide a green, environmentally friendly, energy-saving and efficient visible light catalytic method to synthesize N -methylamide compounds.
- the technical solution adopted by the present invention is: a green visible light catalyzed preparation method of N -methylamide compound, under the catalysis of metal salt, under visible light irradiation, using amide as raw material and hydrochloric acid as additive. , react to prepare N -methylamide compounds.
- the reaction is carried out in a solvent
- the solvent is dimethyl sulfoxide, N , N -dimethylformamide, 1,2-dichloroethane, 1,1,1-trichloroethane, 1, 1,2-trichloroethane, nitromethane, methanol, ethanol, tetrahydrofuran, 2-butanone, benzene, acetonitrile, ethyl acetate, 1,4-dioxane; the preferred solvent is acetone.
- R 1 is selected from alkyl, naphthoxy, benzoyl, substituted or unsubstituted aralkyl, wherein the substituents are nitro, methoxy, cyano, ester, fluorine, chlorine, Trifluoromethyl, trifluoromethoxy, acyl, etc.;
- R 2 is selected from aryl or alkyl.
- the visible light is LED light
- the LED light is white light, green light or blue light
- the wattage is 18W ⁇ 50W.
- reaction time is 12 to 96 hours, and the preferred reaction time is 72 hours.
- the catalyst is copper chloride, cerium chloride, sodium chloride, ferric chloride, lithium chloride, calcium chloride, and silver chloride.
- the catalyst is copper chloride.
- the molar ratio of amide, hydrochloric acid and metal salt is 1: (1-4): (0.01-0.2), preferably 1:2:0.05.
- the reaction substrate is a cheap tertiary amide
- the light source is an economical and easily available LED lamp
- the solvent is acetone
- the catalyst is copper chloride, which can be purchased directly.
- the reaction of the present invention is carried out in oxygen. After the reaction is completed, quench with saturated sodium sulfite, dry with anhydrous sodium sulfate, remove the solvent and silica gel adsorption with a rotary evaporator, and obtain the N -methylamide compound through simple column chromatography.
- the present invention has the following advantages compared with the prior art: the technology of the present invention does not require the use of expensive, pre-prepared catalysts, and the substrate is simple and easy to obtain, thereby avoiding the problem of too cumbersome operation, and Compared with the existing visible light catalysis technology, copper chloride is used as the catalyst to avoid the use of expensive metals or organic macromolecule photocatalysts; compared with the existing technology, this method uses green and cheap oxygen as the oxidant to avoid the use of excessive Oxidizing agent; the technology of the present invention uses easily available tertiary amides as reaction raw materials, which is more practical than the existing technology.
- the operating method of the present invention is a conventional method in this field. It uses amide as a substrate, a metal salt catalyst, hydrochloric acid as an additive, and an organic solvent as the reaction system. No other substances are needed.
- the product N - can be efficiently obtained under visible light irradiation, oxygen or air.
- the invention adopts a green, environmentally friendly, mild, efficient and energy-saving visible light catalysis strategy to synthesize N -methylamide compounds.
- the light source is an economical and easily available LED lamp
- the reaction substrate is a tertiary amide
- an organic solvent
- the catalyst is copper chloride. All are commercial products and can be purchased directly. Unless otherwise specified, the following experiments were conducted in oxygen and room temperature, and the yields are isolated yields.
- the present invention adopts a green, mild and environmentally friendly visible light catalysis mode to prepare N -methylamide compounds.
- Photochemical reaction is a synthesis method with the goal of cleanliness, energy saving and economy. Photochemical reaction generally does not require activation energy, or only requires a small amount of activation energy. At the same time, photochemical reaction can select the corresponding light source according to the different absorption wavelengths of each group in the molecule. , selectively excite a certain group to trigger a reaction; clever use of photochemical reactions can often greatly shorten the synthesis route of the target product.
- the existing technology for synthesizing N -methylamide compounds has a single reaction mode (mostly thermal reactions), narrow reaction substrates, low reaction yields, excessive organic or inorganic additives, and harsh reaction conditions. In comparison, the present invention has the advantages of a wide range of reaction substrates (both aliphatic and aromatic tertiary amides are suitable for this method), simple reaction conditions, relatively high reaction yield, and green and mild reaction conditions.
- Embodiment 1 Embodiment 1
- Embodiment three Embodiment three: .
- Embodiment 4 .
- Embodiment five Embodiment five: .
- Embodiment 6 Embodiment 6: .
- Embodiment 7 Embodiment 7: .
- Embodiment 8 .
- Embodiment 9 Embodiment 9: .
- Embodiment 11 .
- Embodiment 12 .
- Embodiment 13 .
- Example fourteen .
- Embodiment 15 Embodiment 15: .
- Embodiment 16 .
- Embodiment seventeen .
- Embodiment 19 .
- Embodiment 20 .
- Embodiment 21 .
- the "light” in photoreactions is a special reagent that can participate in the reaction.
- photochemical reactions Compared with classic thermochemical reactions, photochemical reactions have the following characteristics: (1) Thermochemical reactions require large activation energy and need to be heated to The reaction can only occur at a certain temperature; the activation energy required for photochemical reactions is very small, so it can proceed quickly at room temperature; (2) Complex molecules often contain multiple active groups. In order for one of the groups to react in a thermochemical reaction, other groups need to be protected; while photochemical reactions can excite specific groups to trigger the reaction; (3) In most cases, the products of thermochemical reactions and photochemical reactions Different, therefore photochemical reactions can be used to synthesize products that cannot be synthesized by thermochemical reactions.
- the light source LED lamp in the reaction system is cheap and easy to obtain, the source of raw materials is abundant, and the reaction substrate has wide applicability (both aliphatic and aromatic amides are compatible with this system).
- the reaction conditions are mild, no oxidant is needed, economical copper chloride is used as the catalyst, easily available tertiary amide is used as the raw material, and the reaction operation is simple.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种绿色的 N-甲基酰胺化合物的制备方法，以LED灯作为光源提供能量，经济易得的三级酰胺作为反应底物，氯化铜为催化剂，市场可购买的盐酸为添加剂，丙酮为溶剂。与现有技术相比较，本发明方法具有以下优点：采用绿色、温和、环境友好的可见光催化的反应模式；反应体系简单且底物范围广，芳香族和脂肪族酰胺均适用于该方法；反应产率较高；操作比较简单、原料廉价易得。
Description
本发明涉及绿色的可见光催化的
N-甲基酰胺化合物的制备方法，属于有机合成技术领域。
N-甲基酰胺类化合物是一类重要的结构骨架，在医药、农用化学品、聚合物、功能性有机材料、天然产物等领域普遍存在。很多药物分子中均含有
N-甲基酰胺骨架，如阿昔替尼（Axitinib）：一种小分子酪氨酸激酶抑制剂，可抑制多种靶标，包括VEGFR-1，VEGFR-2，VEGFR-3，血小板衍生生长因子受体（PDGFR）和cKIT（CD117）；水杨酸毒扁豆碱（Physostigmine
salicylate）：一种可逆的乙酰胆碱酯酶 (AChE) 抑制剂，可以透过血脑屏障并刺激中枢胆碱能神经传递，并且能逆转阿尔茨海默病转基因小鼠的记忆缺陷，除此之外，该药物分子也是抗胆碱能中毒的解毒剂；恩杂鲁胺（Enzalutamide）：一种雄激素受体 (androgen receptor (AR)) 拮抗剂，在
LNCaP 前列腺细胞中抑制AR的IC50值为 36 nM，Enzalutamide是一种自噬 (Autophagy) 激活剂。因此合成
N-甲基酰胺类化合物显得尤为重要。三级酰胺的去甲基化是构建
N-甲基酰胺类化合物的重要方法。通过文献调查发现，这类方法都存在一些明显的不足之处，诸如反应条件苛刻，产率低、底物范围窄、反应高温、使用比较昂贵的金属催化剂、需要过量的氧化剂、反应模式单一（大多为热反应）等。例如：（1）2004年，Iley课题组将四苯基卟啉铁（III）氯化物和叔丁醇结合作为一种高活性的氧化剂，实现了由三级酰胺去甲基化制备
N-甲基酰胺类化合物。该方法底物局限芳香族酰胺，并且铁络合物需要预制备，操作比较繁琐。（2）2014年，Moriyama课题组以过氧单磺酸钾为氧化剂，溴化钾为自由基源，在50℃条件下，实现三级酰胺的去苄基化，该反应中涉及亚铵阳离子的生成。该反应需要当量的氧化剂和无机盐。（3）2015年，Reeves课题组以过量甲磺酸为添加剂，在90℃条件下实现三级酰胺去异丙基化。该反应使用强酸为添加剂，条件苛刻，并且产率较低。（4）2019年，Jones团队，在电化学条件下实现
N,N-二乙基苯甲酰胺的选择性去乙基化。（5）2020年，张玉霞课题组，以乙酰丙酮铜为催化剂，
N-氟代双苯磺酰胺为氧化剂，甲醇为氢源，在80℃下，氮气氛围中实现了三级酰胺的去甲基化。该方法产率较低，底物比较局限，不利于工业上的大规模合成应用。
综上所述，目前报道的这些酰胺去烷基化的方法，反应过程比较繁琐，采用过量的氧化剂、反应条件比较苛刻、反应模式比较单一（绝大多数为热反应）、底物基本局限于芳香族酰胺。因此，发展一种原料来源丰富，底物适应范围广泛、绿色、温和、高效、环境友好的可见光催化的
N-甲基酰胺化合物的制备方法尤为重要。
本发明的目的是提供一种绿色、环境友好、节能高效的可见光催化的方法来合成
N-甲基酰胺化合物。
为达到上述发明目的，本发明采用的技术方案是：一种绿色的可见光催化的
N-甲基酰胺化合物的制备方法，在金属盐催化下，在可见光照射下，以酰胺为原料，盐酸为添加剂，反应制备
N-甲基酰胺化合物。
上述技术方案中，反应在溶剂中进行，溶剂为二甲亚砜、
N,
N-二甲基甲酰胺、1,2-二氯乙烷、1,1,1-三氯乙烷、1,1,2-三氯乙烷、硝基甲烷、甲醇、乙醇、四氢呋喃、2-丁酮、苯、乙腈、乙酸乙酯、1,4-二氧六环；优选溶剂为丙酮。
上述技术方案中，三级酰胺的化学结构式如下：
。
所述
N-甲基酰胺的化学结构式如下：
。
上述化学结构式中，R
1选自烷基、萘氧基、苯甲酰基、取代或未取代的芳烷基，其中取代基为硝基、甲氧基、氰基、酯基、氟、氯、三氟甲基、三氟甲氧基、酰基等；R
2选自芳基或者烷基。
上述技术方案中，所述可见光为LED灯光，LED灯为白灯、绿灯或者蓝灯；瓦数为18W～50W。
本发明中，反应的时间为12～96小时，优选的反应时间为72小时。
本发明中，所述催化剂为氯化铜、氯化铈、氯化钠、氯化铁 氯化锂、氯化钙、氯化银。优选的技术方案中，催化剂为氯化铜。
本发明中，酰胺、盐酸、金属盐的摩尔比为1∶（1～4）∶（0.01～0.2），优选为1∶2∶0.05。
本发明中，反应底物为廉价的三级酰胺、光源为经济易得的LED灯，溶剂为丙酮、催化剂为氯化铜，可以直接购买获得。本发明的反应在氧气中进行。反应结束后，用饱和亚硫酸钠淬灭，无水硫酸钠干燥，用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得
N-甲基酰胺化合物。
由于上述技术方案的运用，本发明与现有技术相比具有下列优点：本发明的技术不需要采用昂贵、预制备的催化剂，底物简单易得，从而避免了操作上过于繁琐的问题，与现有的可见光催化技术相比，使用氯化铜作为催化剂，避免使用昂贵金属或有机大分子光催化剂；，与现有的技术相比，该方法使用绿色廉价的氧气作为氧化剂，避免使用过量的氧化剂；本发明技术使用易得的三级酰胺为反应原料，与现有的技术相比，更具有实用性。
本发明操作方法为本领域常规方法，以酰胺为底物、金属盐催化剂、盐酸为添加剂、有机溶剂为反应体系，无需其他物质，在可见光照射下，氧气或者空气中即可高效得到产物
N-甲基酰胺化合物。本发明采用了绿色、环保、温和、高效、节能的可见光催化的策略来合成
N-甲基酰胺化合物，光源为经济易得的LED灯，反应底物三级酰胺，有机溶剂、催化剂氯化铜皆为商业化产品，可以直接购买获得。如无特殊说明，以下实验都在氧气中、室温下进行，收率为分离收率。
本发明采用绿色、温和、环境友好的可见光催化的模式制备
N-甲基酰胺化合物。光化学反应是以洁净、节能、节约为目标的合成方法，光化学反应一般不需要活化能，或者只需要很小的活化能；同时光化学反应可以根据分子中各个基团吸收波长的不同选择对应的光源，选择性地激发某一基团引发反应的发生；巧妙利用光化学反应往往可以大幅度缩短目标产物的合成路线。现有的合成
N-甲基酰胺化合物的技术中反应模式单一（大多数为热反应）、反应底物窄，反应产率低、需要过量的有机或无机添加剂、反应条件苛刻。与此相比，本发明具有反应底物范围广（脂肪族和芳香族三级酰胺均适用于该方法），反应条件简单、反应产率比较高、反应条件绿色且温和等优点。
下面结合实例对本发明作进一步描述：实施例一：
。
在25 mL Schlenk试管中依次加入酰胺
1a (0.2
mmol，29.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
1b，收率为90%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, CDCl
3) δ 7.79 – 7.77 (m, 2H),
7.46 – 7.42 (m, 1H), 7.37 – 7.33 (m, 2H), 7.09 (s, 1H), 2.94 (d,
J = 4.8 Hz,
2H).
13C NMR
(100 MHz, CDCl
3) δ
13C NMR (100 MHz,
CDCl
3) δ 168.42, 134.34,
131.10, 128.25, 126.79, 26.63.
HRMS (ESI-TOF): Anal Calcd. For. C
8H
9NO+Na
+:
136.0576, Found: 136.0580.
IR (neat, cm
-1): υ 3282, 2940, 1642, 1594, 1489, 1300, 746, 696。
拓展实施例：在实施例一的基础上，进行单因素变化，得到表1的结果。
。
实施例二：
。
在25 mL Schlenk试管中依次加入酰胺
2a (0.2
mmol，36.6 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
2b，收率为86%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, CDCl
3) δ 7.72 – 7.69 (m, 2H),
7.49 – 7.36 (m, 2H), 6.38 (s, 1H), 2.99 (d,
J
= 4.8 Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 165.51, 135.82, 133.22, 128.95, 128.33, 26.24.
HRMS (ESI-TOF):
Anal Calcd. For. C
8H
8
35ClNO+Na
+:
192.0187, Found: 192.0185; Anal Calcd. For. C
8H
8
37ClNO+Na
+:
194.0157, Found: 194.0194.
IR (neat, cm
-1): υ 3343, 1634, 1601, 1545, 1487, 841, 794。
实施例三：
。
在25 mL Schlenk试管中依次加入酰胺
3a (0.2
mmol，46.6 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
3b，收率为66%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.55 (d,
J = 4.1 Hz, 1H), 7.97 – 7.94 (m, 2H), 7.44 – 7.42
(m, 2H), 2.79 (d,
J = 4.6 Hz, 3H).
13C NMR
(100 MHz,
DMSO) δ 165.83, 150.59, 134.04, 129.78, 120.98,
120.42 (q,
J = 255 Hz, 3H), 26.68.
19F NMR
(377 MHz,
DMSO) δ -56.73 (s, 3F).
HRMS (ESI-TOF):
Anal Calcd. For. C
9H
8F
3NO
2 +Na
+:
242.0399, Found: 242.0385.
IR (neat, cm
-1): υ 3326, 3050, 1636, 1586, 1410, 1352, 1207, 840, 762。
实施例四：
。
在25 mL Schlenk试管中依次加入酰胺
4a (0.2
mmol，39.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
4b，收率为79%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.76 (s, 1H), 8.30 (d,
J = 8.8 Hz, 2H), 8.05 (d,
J
= 8.8 Hz, 2H), 2.81 (d,
J = 4.6 Hz, 3H).
13C NMR
(100
MHz, DMSO) δ 164.92, 148.90, 140.09, 128.54, 123.51,
26.38.
HRMS (ESI-TOF): Anal Calcd. For. C
8H
8N
2O
3+Na
+:
203.0427, Found: 203.0425.
IR (neat, cm
-1): υ 3330, 2946, 1645, 1597, 1489, 1347, 824, 780。
实施例五：
。
在25 mL Schlenk试管中依次加入酰胺
5a (0.2
mmol，47.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
5b，收率为50%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.48 (s, 1H), 7.83 –7.77
(m, 2H), 7.66 –7.64 (m, 1H), 2.80 (d,
J = 4.6
Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 162.99 (s, 1H), 158.74 (d,
J = 251.2 Hz), 132.07
(dd,
J = 41.5, 9.0 Hz), 131.28 (d,
J = 3.6 Hz), 128.26 (d,
J
= 15.4 Hz), 123.04 (dd,
J = 272.8, 3.0 Hz), 113.77 (dd,
J = 26.3,
3.8 Hz), 26.20.
19F NMR
(377 MHz, DMSO) δ -61.53 (s, 3F), -112.21 (s, 1F).
HRMS (ESI-TOF):
Anal Calcd. For. C
9H
7F
4NO +Na
+:
244.0356, Found: 244.0363.
IR (neat, cm
-1): υ 3262, 2932, 1635, 1523, 1412, 1331, 879, 778。
实施例六：
。
在25 mL Schlenk试管中依次加入酰胺
6a (0.2
mmol，43.4 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
6b，收率为73%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.68 (s, 1H), 8.02 (d,
J = 8.2 Hz, 2H), 7.82 (d,
J
= 8.2 Hz, 2H), 2.81 (d,
J = 4.6 Hz, 3H).
13C NMR
(100
MHz, DMSO) δ 165.87, 138.71, 131.45 (q,
J =
31.7 Hz), 128.41, 125.76 (q,
J = 3.8 Hz), 123.07, 26.76.
19F
NMR (377 MHz, DMSO) δ -61.38 (s, 3F).
HRMS (ESI-TOF): Anal Calcd. For. C
9H
8F
3NO
+H
+: 204.0631, Found: 204.0627.
IR (neat, cm
-1): υ 3334, 3082, 1635, 1556, 1495, 1360, 846, 776。
实施例七：
。
在25 mL Schlenk试管中依次加入酰胺
7a (0.2
mmol，33.4 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
7b，收率为66%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.44 (s, 1H), 7.91 – 7.87
(m, 2H), 7.30 – 7.25 (m, 2H), 2.78 (d,
J = 4.6
Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 165.52, 163.72 (d,
J = 248.0 Hz), 130.97 (d,
J
= 2.9 Hz, 1H), 129.61 (d,
J = 8.9 Hz, 4H), 115.14 (d,
J = 21.7
Hz, 5H), 26.23.
19F NMR (377 MHz, DMSO)
δ
-109.88 (s, 1F).HRMS (ESI-TOF): Anal
Calcd. For. C
8H
8FNO+Na
+: 176.0482, Found:
176.0489.
IR (neat, cm
-1): υ
3346, 1634, 1589, 1436, 1319, 845, 793。
实施例八：
。
在25 mL Schlenk试管中依次加入酰胺
8a (0.2
mmol，46.6 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
8b，收率为53%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.36 (s, 1H), 7.60 – 7.56
(m, 2H), 7.47 – 7.40 (m, 2H), 2.76 (d,
J = 4.6
Hz, 1H).
13C NMR
(100 MHz, DMSO) δ 165.03, 144.86 (q,
J = 1.7 Hz), 131.35, 131.19,
129.62, 127.51, 121.54, 120.03 (q,
J = 256.8 Hz), 26.02.
19F
NMR
(377 MHz, DMSO) δ -56.51 (s, 3F).
HRMS (ESI-TOF): Anal Calcd. For. C
9H
8F
3NO
2
+Na
+: 242.0399, Found: 242.0401.
IR (neat, cm
-1): υ 3282, 2950, 1646, 1593, 1444, 1321, 1250, 765, 698。
实施例九：
。
在25 mL Schlenk试管中依次加入酰胺
9a (0.2
mmol，34.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
9b，收率为57%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (300 MHz, DMSO) δ 8.68 (s, 1H), 7.99 – 7.93
(m, 4H), 2.80 (d,
J = 4.6 Hz, 3H).
13C NMR (75 MHz, DMSO)
δ
165.20, 138.44, 132.44, 127.91, 118.35, 113.46,
26.35.HRMS (ESI-TOF): Anal Calcd. For. C
9H
8N
2O+Na
+:
183.0529, Found: 183.0525.
IR (neat, cm
-1): υ 3336, 2943, 2227, 1722, 1638, 1550, 1498, 1349, 854, 760。
实施例十：
。
在25 mL Schlenk试管中依次加入酰胺
10a (0.2
mmol，33.4 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
10b，收率为74%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.53 (d,
J = 2.6 Hz, 1H), 7.70 – 7.68 (m, 1H), 7.64 – 7.61
(m, 1H), 7.52 – 7.47 (m, 1H), 7.36 – 7.31 (m, 1H), 2.79 (d,
J = 4.6 Hz, 3H).
13C
NMR
(100 MHz, DMSO) δ 165.31 (d,
J
= 2.5 Hz), 162.01 (d,
J = 244.1 Hz), 136.93 (d,
J = 6.8 Hz),
130.38 (d,
J = 8.0 Hz), 123.18 (d,
J = 2.8 Hz), 117.86 (d,
J
= 21.1 Hz), 113.90 (d,
J = 22.7 Hz), 26.25.
19F NMR
(377
MHz, DMSO) δ -112.90 (s, 1F).
HRMS (ESI-TOF):
Anal Calcd. For. C
8H
8FNO+Na
+: 176.0482, Found:
176.0478.
IR (neat, cm
-1): υ
3335, 2947, 1634, 1552, 1488, 1301, 892, 802, 792。
实施例十一：
。
在25 mL Schlenk试管中依次加入酰胺
11a (0.2
mmol，44.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
11b，收率为51%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.48 (d,
J = 4.2 Hz, 1H), 8.07 (d,
J = 9.1
Hz, 1H), 7.15 (dd,
J = 9.1, 2.8 Hz, 1H), 7.05 (d,
J = 2.8 Hz,
1H), 3.90 (s, 3H), 2.75 (d,
J = 4.7 Hz, 3H).
13C NMR
(75 MHz, DMSO) δ 165.91, 163.05,
139.29, 135.75, 126.79, 114.91, 114.06, 56.39, 26.06.
HRMS (ESI-TOF):
Anal Calcd. For. C
9H
10N
2O
4 +Na
+:
233.0533, Found: 233.0540.
IR (neat, cm
-1): υ 3270, 2943, 1637, 1563, 1509, 1405, 1323, 888, 830, 796。
实施例十二：
。
在25 mL Schlenk试管中依次加入酰胺
12a (0.2
mmol，47.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
12b，收率为61%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (300 MHz, DMSO) δ 8.47 (d,
J = 4.2 Hz, 1H), 7.88 (d,
J = 6.6
Hz, 1H), 7.59 (d,
J = 9.1 Hz, 1H), 2.75 (d,
J = 4.7 Hz, 3H).
13C
NMR
(75 MHz, DMSO) δ 164.70, 155.84
(d,
J = 248.3 Hz), 137.37 (d,
J = 6.3 Hz, 1H), 131.20, 126.09 (d,
J = 3.7 Hz, 1H), 121.25 (d,
J = 18.8 Hz, 1H), 117.10 (d,
J
= 23.8 Hz, 2H), 25.97.
19F NMR
(377 MHz, DMSO) δ -117.73 (s, 1F).
HRMS (ESI-TOF): Anal Calcd. For.
C
8H
6
35Cl
2FNO+Na
+:
243.9703, Found: 243.9700. Anal Calcd. For. C
8H
6
35,37Cl
2
FNO+Na
+:
245.9673, Found: 245.9671.
IR (neat, cm
-1): υ 3295, 2854, 1752, 1645, 1553, 1469, 1309, 950, 886。
实施例十三：
。
在25 mL Schlenk试管中依次加入酰胺
13a (0.2
mmol，41.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
13b，收率为51%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.72 (d,
J = 4.1 Hz, 1H), 8.02 – 7.99 (m, 2H), 7.94 – 7.91
(m, 1H), 7.47 – 7.40 (m, 2H), 2.81 (d,
J = 4.6
Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 161.89, 140.05, 139.16, 126.07, 125.08, 124.86, 124.36,
122.77, 26.19.
HRMS (ESI-TOF): Anal Calcd. For. C
10H
9NOS+Na
+:
214.0297, Found: 214.0309.
IR (neat, cm
-1): υ 3314, 3060, 1626, 1557, 1495, 1300, 757。
实施例十四：
。
在25 mL Schlenk试管中依次加入酰胺
14a (0.2
mmol，37.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
14b，收率为70%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.53 (d,
J = 3.7 Hz, 1H), 7.56 (d,
J = 4.0
Hz, 1H), 7.16 (d,
J = 4.0 Hz, 1H), 2.74 (d,
J = 4.6 Hz, 3H).
13C
NMR
(100 MHz, DMSO) δ 160.50, 139.21,
132.55, 128.00, 127.54, 25.93.
HRMS (ESI-TOF): Anal Calcd. For. C
6H
6
35ClNOS+Na
+:
197.9751, Found: 197.9750. Anal Calcd. For. C
6H
6
37ClNOS+Na
+:
199.9721, Found: 199.9718.
IR (neat, cm
-1): υ 3282, 2982, 1645, 1593, 1429, 1299, 812, 791。
实施例十五：
。
在25 mL Schlenk试管中依次加入酰胺
15a (0.2
mmol，65.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
15b，收率为68%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 7.42 (d,
J = 4.5 Hz, 1H), 7.25 – 7.14 (m, 15H), 3.54 (s, 2H), 2.26 (d,
J = 4.6 Hz,
3H).
13C NMR
(100 MHz, DMSO)
δ
170.05, 147.26, 129.16, 127.41, 125.74, 55.79,
46.43, 25.30.
HRMS (ESI-TOF): Anal
Calcd. For. C
22H
21NO+Na
+: 338.1515, Found:
338.1523.
IR (neat, cm
-1): υ
3262, 2935, 1657, 1594, 1407, 1363, 763, 695。
实施例十六：
。
在25 mL Schlenk试管中依次加入酰胺
16a (0.2
mmol，45.8 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
16b，收率为50%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.42 – 8.40 (m, 1H),
8.09 (s, 1H), 7.89 – 7.87 (m, 1H),
7.55 – 7.50 (m, 3H), 7.43 – 7.39 (m, 1H), 6.91 (d,
J = 7.3 Hz, 1H), 4.66 (s,
2H), 2.72 (d,
J = 4.7 Hz, 3H).
13C NMR
(100 MHz, DMSO)
δ 167.79, 153.17, 134.03, 127.33, 126.54,
126.03, 125.26, 124.75, 122.20, 120.66, 105.59, 67.39, 25.50.
HRMS (ESI-TOF):
Anal Calcd. For. C
13H
13NO
2 +Na
+:
238.0838, Found: 238.0841.
IR (neat, cm
-1): υ 3262, 2937, 1655, 1572, 1457, 1348, 1264, 765, 682。
实施例十七：
。
在25 mL Schlenk试管中依次加入酰胺
17a (0.2
mmol，42.6 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
17b，收率为57%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.72 (d,
J = 4.4 Hz, 1H), 7.78 (d,
J = 4.0
Hz, 1H), 7.71 (d,
J = 4.0 Hz, 1H), 3.83 (s, 1H), 2.78 (d,
J = 4.6
Hz, 3H).
13C NMR (101 MHz, DMSO) δ
161.61, 160.62, 146.07, 135.30, 133.88, 127.98, 52.50, 26.09.
HRMS (ESI-TOF):
Anal Calcd. For. C
8H
9NO
3S +Na
+:
222.0195, Found: 222.0196.
IR (neat, cm
-1): υ 3262, 2937, 1654, 1572, 1480, 1348, 1264, 820, 730。
实施例十八：
。
在25 mL Schlenk试管中依次加入酰胺
18a (0.2
mmol，50.2 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
18b，收率为59%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.60 (d,
J = 4.4 Hz, 1H), 7.74 (s, 2H), 2.77 (d,
J
= 4.7 Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 163.30, 135.74, 134.23, 132.04, 127.88, 25.79.
HRMS (ESI-TOF):
Anal Calcd. For. C
8H
6
35Cl
3NO +Na
+:
259.09407, Found: 259.9410. Anal Calcd. For. C
8H
6
35,35,37Cl
3
NO
+Na
+: 261.9378, Found: 261.9356. Anal Calcd. For. C
8H
6
35,37,37Cl
3
NO
+Na
+: 263.9348, Found: 263.9298.
IR (neat, cm
-1): υ 3280, 2943, 1646, 1546, 1488, 1309, 920, 849。
实施例十九：
。
在25 mL Schlenk试管中依次加入酰胺
19a (0.2
mmol，43.4 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
19b，收率为52%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.40 (d,
J = 4.1 Hz, 1H), 7.67 (d,
J = 1.8
Hz, 1H), 7.49 – 7.43 (m, 2H),
2.75 (d,
J = 4.7 Hz, 3H).
13C NMR (100 MHz, DMSO)
δ
165.81, 135.87, 134.36, 131.10, 130.21, 129.10, 127.28,
25.96.HRMS (ESI-TOF): Anal Calcd. For. C
8H
7
35Cl
2NO+Na
+:
225.9797, Found: 225.9800. Anal Calcd. For. C
8H
7
37,35Cl
2
NO+Na
+:
227.9767, Found: 227.9760. Anal Calcd. For. C
8H
7
35Cl
2NO+Na
+:
229.9738, Found: 229.9731.
IR (neat, cm
-1): υ 3282, 2981, 1646, 1592, 1444, 1321, 881, 828, 788。
实施例二十：
。
在25 mL Schlenk试管中依次加入酰胺
20a (0.2
mmol，37.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
20b，收率为49%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 8.62 (s, 1H), 7.52 – 7.46
(m, 1H), 7.18 – 7.13 (m, 2H), 2.77 (d,
J = 4.7
Hz, 3H).
13C NMR
(100 MHz, DMSO) δ 160.03 (t,
J = 4.1 Hz), 157.57 (d,
J = 8.1
Hz), 131.45 (t,
J = 10.0 Hz), 115.55 (t,
J = 23.2 Hz), 111.86
(dd,
J = 13.0, 6.0 Hz), 25.94.
19F NMR
(377 MHz, DMSO)
δ -114.18 (s, 2F).
HRMS (ESI-TOF):
Anal Calcd. For. C
8H
7F
2NO +Na
+:
194.0388, Found: 194.0380.
IR (neat, cm
-1): υ 3280, 2881, 1646, 1593, 1488, 1325, 1299, 845, 766。
实施例二十一：
。
在25 mL Schlenk试管中依次加入酰胺
22a (0.2
mmol，41.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
22b，收率为57%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (300 MHz, DMSO) δ 9.76 (s, 1H), 7.58 (d,
J = 8.0 Hz, 2H), 7.28 (t,
J
= 8.0 Hz, 2H), 7.02 (t,
J = 7.4 Hz, 1H), 2.18 (s, 2H), 1.02 (s, 9H).
13C
NMR
(75 MHz, DMSO) δ 169.97, 139.25,
128.61, 122.98, 119.19, 49.60, 30.84, 29.63.
HRMS (ESI-TOF): Anal Calcd.
For. C
12H
17NO +Na
+: 214.1202, Found: 214.1209.
IR (neat, cm
-1): υ
3262, 2937, 1654, 1573, 1434, 1348, 730, 683。
实施例二十二：
。
在25 mL Schlenk试管中依次加入酰胺
23a (0.2
mmol，35.0 mg)、盐酸 (0.4
mmol，39.5 mg)、 氯化铜（0.05 mmol，1.3 mg）、丙酮 (0.5 mL)中；然后在38W白光LED照射下，氧气氛围中，常规搅拌72小时后，反应体系用饱和亚硫酸钠溶液淬灭，用乙酸乙酯萃取3次，合并有机层，用无水硫酸钠干燥。用旋转蒸发仪除去溶剂、硅胶吸附，通过简单的柱层析即可得产物
23b，收率为80%。所制得产物的主要测试数据如下，通过分析可知，实际合成产物与理论分析一致。
1 (400 MHz, DMSO) δ 10.16 (s, 1H), 7.58 (d,
J = 7.6 Hz, 2H), 7.30 – 7.26 (m, 2H), 7.01 (t,
J = 7.6 Hz, 1H), 1.80 – 1.74 (m, 1H), 0.80 – 0.76
(m, 4H).
13C NMR
(100 MHz, DMSO) δ 171.55, 139.34, 128.65, 122.85, 118.93, 14.50, 7.09.
HRMS
(ESI-TOF): Anal Calcd. For. C
10H
11NO+Na
+:
184.0733, Found: 184.0727.
IR (neat, cm
-1): υ 3277, 2960, 1651, 1540, 1439, 1307, 754, 693。
光反应中的“光”是一种特殊的、能够参与反应的试剂，与经典的热化学反应相比，光化学反应具有以下特点：（1）热化学反应需要较大的活化能，需要加热到一定温度反应才能发生；而光化学反应所需活化能很小，因此在室温下可以快速进行；（2）复杂的分子往往含有多个活性基团。热化学反应中要使其中某一个基团发生反应，需要将其它基团保护起来；而光化学反应可激发特定基团来引发反应的发生；（3）多数情况下热化学反应与光化学反应的产物不同，因此可利用光化学反应合成热化学反应不能合成的产物。基于光化学反应的这些性质，本发明的优越性显而易见，该反应体系中光源LED灯廉价易得、原料来源丰富、反应底物普适性广（脂肪族和芳香族酰胺均兼容于该体系）、反应条件温和、无需任何氧化剂、经济的氯化铜为催化剂、易得的三级酰胺作为原料、反应操作简便。
Claims (10)
- 一种绿色的 N-甲基酰胺化合物的制备方法，其特征在于，在金属盐催化下，在可见光照射下，以酰胺为原料，盐酸为添加剂，反应制备 N-甲基酰胺化合物。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，所述酰胺的化学结构式如下：式中，R 1选自烷基、萘氧基、苯甲酰基、取代或未取代的芳烷基；R 2选自芳基或者烷基。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，所述 N-甲基酰胺的化学结构式如下：式中，R 1选自烷基、萘氧基、苯甲酰基、取代或未取代的芳烷基。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，反应在溶剂中进行，溶剂为二甲亚砜、 N, N-二甲基甲酰胺、1,2-二氯乙烷、1,1,1-三氯乙烷、1,1,2-三氯乙烷、硝基甲烷、甲醇、乙醇、四氢呋喃、2-丁酮、苯、乙腈、乙酸乙酯、1,4-二氧六环、丙酮中的一种或几种。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，反应的时间为12～96小时。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，所述金属盐为金属卤化物。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，所述反应在氧气或者空气中进行。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法，其特征在于，酰胺、盐酸、金属盐的摩尔比为1∶（1～4）∶（0.01～0.2）。
- 根据权利要求1所述绿色的 N-甲基酰胺化合物的制备方法制备的 N-甲基酰胺化合物。
- 在金属盐催化下，在可见光照射下，酰胺为原料在制备权利要求9所述 N-甲基酰胺化合物中的应用。
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