CN113173921B - A kind of 6-thienyl pyridone compound and its synthetic method - Google Patents
A kind of 6-thienyl pyridone compound and its synthetic method Download PDFInfo
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- -1 6-thienyl pyridone compound Chemical class 0.000 title claims abstract description 46
- 238000010189 synthetic method Methods 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 62
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- 229930192474 thiophene Natural products 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000000654 additive Substances 0.000 claims abstract description 8
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- 230000000996 additive effect Effects 0.000 claims abstract description 7
- 230000001590 oxidative effect Effects 0.000 claims abstract description 5
- 239000012752 auxiliary agent Substances 0.000 claims abstract 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 48
- 239000002904 solvent Substances 0.000 claims description 26
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- 229960000583 acetic acid Drugs 0.000 claims description 6
- 239000012362 glacial acetic acid Substances 0.000 claims description 6
- 239000005711 Benzoic acid Substances 0.000 claims description 5
- 235000010233 benzoic acid Nutrition 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 101710134784 Agnoprotein Proteins 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims 1
- 238000001308 synthesis method Methods 0.000 claims 1
- 239000010948 rhodium Substances 0.000 abstract description 24
- OYXVCXRBUVWISS-UHFFFAOYSA-N 6-thiophen-2-yl-1h-pyridin-2-one Chemical class N1C(=O)C=CC=C1C1=CC=CS1 OYXVCXRBUVWISS-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 3
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 229910052703 rhodium Inorganic materials 0.000 abstract description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 abstract description 2
- 150000007524 organic acids Chemical class 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- 230000035484 reaction time Effects 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 23
- TTYWSMWHPYKDEW-UHFFFAOYSA-N 1-pyridin-2-ylpyridin-2-one Chemical class O=C1C=CC=CN1C1=CC=CC=N1 TTYWSMWHPYKDEW-UHFFFAOYSA-N 0.000 description 19
- QENGPZGAWFQWCZ-UHFFFAOYSA-N Methylthiophene Natural products CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 15
- XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 13
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 13
- 229910001544 silver hexafluoroantimonate(V) Inorganic materials 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 3
- 238000006254 arylation reaction Methods 0.000 description 3
- WIKQEUJFZPCFNJ-UHFFFAOYSA-N carbonic acid;silver Chemical compound [Ag].[Ag].OC(O)=O WIKQEUJFZPCFNJ-UHFFFAOYSA-N 0.000 description 3
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 3
- KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- WYJOVVXUZNRJQY-UHFFFAOYSA-N 2-Acetylthiophene Chemical compound CC(=O)C1=CC=CS1 WYJOVVXUZNRJQY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000010499 C–H functionalization reaction Methods 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003577 thiophenes Chemical class 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- SYSYXIVGMQVZLK-UHFFFAOYSA-N 1-pyridin-2-yl-3-(trifluoromethyl)pyridin-2-one Chemical compound O=C1C(C(F)(F)F)=CC=CN1C1=CC=CC=N1 SYSYXIVGMQVZLK-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- ATRJNSFQBYKFSM-UHFFFAOYSA-N 2,3-dibromothiophene Chemical compound BrC=1C=CSC=1Br ATRJNSFQBYKFSM-UHFFFAOYSA-N 0.000 description 1
- YYJBWYBULYUKMR-UHFFFAOYSA-N 2-bromo-3-methylthiophene Chemical compound CC=1C=CSC=1Br YYJBWYBULYUKMR-UHFFFAOYSA-N 0.000 description 1
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
- KQFADYXPELMVHE-UHFFFAOYSA-N 2-chloro-3-methylthiophene Chemical compound CC=1C=CSC=1Cl KQFADYXPELMVHE-UHFFFAOYSA-N 0.000 description 1
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 description 1
- PJRGDKFLFAYRBV-UHFFFAOYSA-N 2-phenylthiophene Chemical compound C1=CSC(C=2C=CC=CC=2)=C1 PJRGDKFLFAYRBV-UHFFFAOYSA-N 0.000 description 1
- QMUPGQBCYLNTNY-UHFFFAOYSA-N 2-pyridin-2-ylisoquinolin-1-one Chemical compound N1=C(C=CC=C1)N1C(C2=CC=CC=C2C=C1)=O QMUPGQBCYLNTNY-UHFFFAOYSA-N 0.000 description 1
- ZGWCKLUGOIEJIA-UHFFFAOYSA-N 3-bromo-1-pyridin-2-ylpyridin-2-one Chemical compound N1=C(C=CC=C1)N1C(C(=CC=C1)Br)=O ZGWCKLUGOIEJIA-UHFFFAOYSA-N 0.000 description 1
- YPHWAKRUBRYZDG-UHFFFAOYSA-N 3-chloro-1-pyridin-2-ylpyridin-2-one Chemical compound Clc1cccn(-c2ccccn2)c1=O YPHWAKRUBRYZDG-UHFFFAOYSA-N 0.000 description 1
- DIBMXFGAWWMELD-UHFFFAOYSA-N 3-fluoro-1-pyridin-2-ylpyridin-2-one Chemical compound Fc1cccn(-c2ccccn2)c1=O DIBMXFGAWWMELD-UHFFFAOYSA-N 0.000 description 1
- UOGLWYUGKCBRAQ-UHFFFAOYSA-N 3-methyl-1-pyridin-2-ylpyridin-2-one Chemical compound O=C1C(C)=CC=CN1C1=CC=CC=N1 UOGLWYUGKCBRAQ-UHFFFAOYSA-N 0.000 description 1
- HROFLEXHTIUZJZ-UHFFFAOYSA-N 3-thiophen-3-yl-2H-isoquinolin-1-one Chemical group O=c1[nH]c(cc2ccccc12)-c1ccsc1 HROFLEXHTIUZJZ-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Chemical group CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
技术领域technical field
本发明涉及有机化工及精细化工领域，特别涉及一种铑催化的，以N-(2-吡啶基)-2-吡啶酮化合物及噻吩为原料，简单高效的合成6-噻吩基吡啶酮化合物的方法。The invention relates to the fields of organic chemical industry and fine chemical industry, in particular to a rhodium-catalyzed method for synthesizing 6-thienyl pyridone compound simply and efficiently using N-(2-pyridyl)-2-pyridone compound and thiophene as raw materials method.
背景技术Background technique
2-吡啶酮是一种广泛存在于生理活性分子及天然产物分子中的杂环结构。因此，对吡啶酮结构的合成及衍生化方法的研究吸引了许多化学及药物合成领域的工作者。这其中，最为实用、可靠的方法是钯催化卤代吡啶酮与金属有机试剂的交叉偶联反应(L.A.Hasvold,W.Wang,S.L.Gwaltney,T.W.Rockway,L.T.G.Nelson,R.A.Mantei,S.A.Fakhoury,G.M.Sullivan,Q.Li,N.-H.Lin,L.Wang,H.Zhang,J.Cohen,W.-Z.Gu,K.Marsh,J.Bauch,S.Rosenberg,H.L.Sham,Bioorg.Med.Chem.Lett.2003,13,4001；C.Bengtsson,F.Almqvist,J.Org.Chem.2010,75,972；M.D.Hill,M.Movassaghi,Chem.Eur.J.2008,14,6836.)。2-Pyridone is a heterocyclic structure that widely exists in physiologically active molecules and natural product molecules. Therefore, the research on the synthesis and derivatization of pyridone structures has attracted many workers in the fields of chemical and pharmaceutical synthesis. Among them, the most practical and reliable method is the cross-coupling reaction of palladium-catalyzed halopyridone with metal organic reagents (L.A.Hasvold, W.Wang, S.L.Gwaltney, T.W.Rockway, L.T.G.Nelson, R.A.Mantei, S.A.Fakhoury, G.M.Sullivan , Q.Li, N.-H.Lin, L.Wang, H.Zhang, J.Cohen, W.-Z.Gu, K.Marsh, J.Bauch, S.Rosenberg, H.L.Sham, Bioorg.Med. Chem. Lett. 2003, 13, 4001; C. Bengtsson, F. Almqvist, J. Org. Chem. 2010, 75, 972; M. D. Hill, M. Movassaghi, Chem. Eur. J. 2008, 14, 6836.).
近年来，过渡金属催化的C-H活化官能化反应，由于不需要卤化预官能化及较毒的过量金属有机试剂，在杂环的衍生化领域发挥了举足轻重的作用。如镍、锰或钯催化的2-吡啶酮的C-3烷基化、芳基化反应；钯催化2-吡啶酮的C-4位芳基化、烯基化反应以及镍、铜催化2-吡啶酮C-6的烷基化、烯基化、芳基化反应等(Y.Chen,F.Wang,A.Jia,X.Li,Chem.Sci.2012,3,3231；Y.Nakao,H.Idei,K.S.Kanyiva,T.Hiyama,J.Am.Chem.Soc.2009,131,15996；A.Nakatani,K.Hirano,T.Satoh,M.Miura,J.Org.Chem.2014,79,1377；E.A.Anagnostaki,A.D.Fotiadou,V.Demertzidou,A.L.Zografos,Chem.Commun.2014,50,6879.)。In recent years, transition metal-catalyzed C-H activated functionalization reactions have played a pivotal role in the derivatization of heterocycles because they do not require halogenated pre-functionalization and excess toxic metal-organic reagents. Such as nickel, manganese or palladium-catalyzed C-3 alkylation and arylation of 2-pyridone; palladium-catalyzed C-4 arylation and alkenylation of 2-pyridone, and nickel and copper catalyzed 2 - Alkylation, alkenylation, arylation of pyridone C-6, etc. (Y. Chen, F. Wang, A. Jia, X. Li, Chem. Sci. 2012, 3, 3231; Y. Nakao , H.Idei, K.S.Kanyiva, T.Hiyama, J.Am.Chem.Soc.2009,131,15996; A.Nakatani, K.Hirano, T.Satoh, M.Miura, J.Org.Chem.2014, 79, 1377; E.A. Anagnostaki, A.D. Fotiadou, V. Demertzidou, A.L. Zografos, Chem. Commun. 2014, 50, 6879.).
发明内容SUMMARY OF THE INVENTION
本发明的目的是：提供一种简单的，铑催化以N-吡啶基-2-吡啶酮化合物及噻吩化合物为原料，合成6-噻吩基2-吡啶酮化合物的方法。本发明以N-吡啶基作为定位基团，通过过渡金属催化的方式实现2-吡啶酮C-6位的C-H活化，并与噻吩反应，通过脱氢偶联形成C-C键。原料来源广，合成容易，方法简单，易于分离纯化。The purpose of the present invention is to provide a simple, rhodium-catalyzed method for synthesizing 6-thienyl-2-pyridone compounds using N-pyridyl-2-pyridone compounds and thiophene compounds as raw materials. The present invention uses N-pyridyl as a positioning group, realizes C-H activation at C-6 position of 2-pyridone by means of transition metal catalysis, reacts with thiophene, and forms C-C bond through dehydrogenation coupling. The source of raw materials is wide, the synthesis is easy, the method is simple, and it is easy to separate and purify.
本发明提供一种6-噻吩基吡啶酮化合物的合成方法，以N-(2-吡啶基)-2-吡啶酮化合物及噻吩化合物为原料，在催化剂、催化剂助剂、氧化剂和添加剂参与下进行合成反应，得到6-噻吩基吡啶酮化合物。The invention provides a method for synthesizing a 6-thienyl pyridone compound, which takes N-(2-pyridyl)-2-pyridone compound and a thiophene compound as raw materials, and carries out the process with the participation of a catalyst, a catalyst assistant, an oxidant and an additive. The synthesis reaction yields the 6-thienylpyridone compound.
该反应的具体工艺过程如下所示：The specific technological process of this reaction is as follows:
其中，R1为甲基、氟、氯、溴、三氟甲基；Wherein, R 1 is methyl, fluorine, chlorine, bromine, trifluoromethyl;
R2为氯、溴、甲基、氰基、乙酰基、甲氧羰基、苯基。R 2 is chlorine, bromine, methyl, cyano, acetyl, methoxycarbonyl, phenyl.
本发明具体的反应条件为：在空气氛围，50-80℃的加热条件下反应，历时6-12小时合成6-噻吩基吡啶酮化合物。The specific reaction conditions of the present invention are as follows: in an air atmosphere, the reaction is carried out under a heating condition of 50-80° C., and the 6-thienyl pyridone compound is synthesized for 6-12 hours.
N-(2-吡啶基)-2-吡啶酮化合物与噻吩化合物的摩尔比为1：1.2-3。The molar ratio of the N-(2-pyridyl)-2-pyridone compound to the thiophene compound is 1:1.2-3.
N-(2-吡啶基)-2-吡啶酮化合物的反应浓度为0.2mmol/3mL四氢呋喃溶剂。The reaction concentration of N-(2-pyridyl)-2-pyridone compound was 0.2 mmol/3 mL of tetrahydrofuran solvent.
N-(2-吡啶基)-2-吡啶酮化合物的结构式为：
噻吩为噻吩环上有氰基、甲基、氯、溴、乙酰基、甲酸乙酯基、苯基取代的噻吩，或者是苯并噻吩中的一种。Thiophene is a thiophene substituted with cyano, methyl, chlorine, bromine, acetyl, ethyl formate and phenyl on the thiophene ring, or one of benzothiophenes.
催化剂为Cp*Rh(OAc)2、[Cp*RhCl2]2、[Cp*Rh(MeCN)2][SbF6]2、[Cp*Rh(MeCN)2]中的一种，催化剂的用量为N-(2-吡啶基)-2-吡啶酮化合物摩尔数的5％，催化剂助剂AgSbF6的用量为N-(2-吡啶基)-2-吡啶酮化合物摩尔数的25mol％。The catalyst is one of Cp * Rh(OAc) 2 , [Cp * RhCl 2 ] 2 , [Cp * Rh(MeCN) 2 ][SbF 6 ] 2 , [Cp * Rh(MeCN) 2 ], and the amount of catalyst used It is 5% of the mole number of N-(2-pyridyl)-2-pyridone compound, and the amount of catalyst assistant AgSbF 6 is 25mol% of the mole number of N-(2-pyridyl)-2-pyridone compound.
氧化剂为Ag2O、Ag2CO3、AgNO3、AgOAc中的一种，氧化剂的用量为N-(2-吡啶基)-2-吡啶酮化合物摩尔数的1-3倍。The oxidizing agent is one of Ag 2 O, Ag 2 CO 3 , AgNO 3 and AgOAc, and the amount of the oxidizing agent is 1-3 times the mole number of the N-(2-pyridyl)-2-pyridone compound.
添加剂为冰醋酸、三氟乙酸、苯甲酸、特戊酸中的一种，添加剂的用量为N-(2-吡啶基)-2-吡啶酮化合物摩尔数的2-5倍。The additive is one of glacial acetic acid, trifluoroacetic acid, benzoic acid and pivalic acid, and the dosage of the additive is 2-5 times the mole number of the N-(2-pyridyl)-2-pyridone compound.
有益效果：Beneficial effects:
1、本发明首次实现了6-噻吩基吡啶酮类化合物的系统合成，为该类结构的合成提供了一条可靠途径。1. The present invention realizes the systematic synthesis of 6-thienyl pyridone compounds for the first time, and provides a reliable way for the synthesis of such structures.
2、反应以N-(2-吡啶基)-2-吡啶酮化合物为原料，其中N上保护基2-吡啶基为反应的导向基团，通过与铑配位作用实现吲哚酮C-6位的C-H活化，该定位基可以通过简单的还原法轻松去除，得到有活性N-H键的6-噻吩基2-吡啶酮结构。这种结构有较高的反应活性。例如，3ha脱吡啶基后得到的3-噻吩基异喹啉酮结构可以用于合成拓扑异构酶抑制剂。2. The reaction uses N-(2-pyridyl)-2-pyridone compound as raw material, wherein the protective group 2-pyridyl on N is the guiding group of the reaction, and indolinone C-6 is realized by coordination with rhodium C-H activation, which can be easily removed by a simple reduction method, yielding a 6-thienyl 2-pyridone structure with an active N-H bond. This structure has high reactivity. For example, the 3-thienylisoquinolinone structure obtained after depyridylation of 3ha can be used to synthesize topoisomerase inhibitors.
3、本发明反应不像大多数的过渡金属催化脱氢偶联反应一样需要惰性气体的保护，该反应在空气下反应效果良好，经济性强，实用性高。3. The reaction of the present invention does not require the protection of an inert gas like most of the transition metal-catalyzed dehydrogenation coupling reactions. The reaction has a good reaction effect in the air, strong economy and high practicability.
具体实施方式Detailed ways
下面结合实施例对本发明进行详细的说明，本发明各实施例反应如下：Below in conjunction with embodiment, the present invention is described in detail, and each embodiment of the present invention reacts as follows:
本发明采用的原料N-(2-吡啶基)-2-吡啶酮化合物、催化剂Cp*Rh(OAc)2根据文献合成得到(H.Zhao,X.Xu,L.Xu,Q.Fan,P.J.Walsh.Org.Lett.2020,22,4228；J.W.Kang,K.Moseley,P.M.Maitlis.J.Am.Chem.Soc.1969,91,5970–5977)；噻吩化合物、催化剂助剂AgSbF6、氧化剂、添加剂以及四氢呋喃均为市售。The raw material N-(2-pyridyl)-2-pyridone compound and catalyst Cp*Rh(OAc) 2 used in the present invention are synthesized according to the literature (H.Zhao, X.Xu, L.Xu, Q.Fan, PJWalsh .Org.Lett.2020, 22, 4228; JW Kang, K. Moseley, PM Maitlis. J. Am. Chem. Soc. 1969, 91, 5970-5977); thiophene compounds, catalyst promoter AgSbF 6 , oxidizing agents, additives and tetrahydrofuran All are commercially available.
实施例1Example 1
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率为73％。1H NMR(300MHz,CDCl3)δ8.51-8.49(m,1H),7.71(td,J＝7.7,1.9Hz,1H),7.34(dd,J＝9.3,7.0Hz,1H),7.28-7.20(m,2H),6.55(dd,J＝9.3,1.2Hz,1H),6.40-6.37(m,2H),6.33(dd,J＝7.0,1.2Hz,1H),2.27(s,3H).13CNMR(75MHz,CDCl3)δ163.4,152.1,149.6,142.9,142.4,139.9,138.4,133.4,129.2,125.5,124.5,124.1,120.1,108.1,15.1.Under air condition, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 73%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.51-8.49 (m, 1H), 7.71 (td, J=7.7, 1.9 Hz, 1H), 7.34 (dd, J=9.3, 7.0 Hz, 1H), 7.28- 7.20(m, 2H), 6.55(dd, J=9.3, 1.2Hz, 1H), 6.40-6.37(m, 2H), 6.33(dd, J=7.0, 1.2Hz, 1H), 2.27(s, 3H) . 13 CNMR (75MHz, CDCl 3 ) δ 163.4, 152.1, 149.6, 142.9, 142.4, 139.9, 138.4, 133.4, 129.2, 125.5, 124.5, 124.1, 120.1, 108.1, 15.1.
实施例2Example 2
在空气条件下，将3-氟-2H-[1,2'-联吡啶]-2-酮1b(0.2mmol)、2-甲基噻吩2a(0.24mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、Ag2O(0.2mmol)、特戊酸(0.3mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到60℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ba，产率为66％。1H NMR(300MHz,CDCl3)δ8.49(d,J＝3.7Hz,1H),7.73(td,J＝7.7,1.9Hz,1H),7.30-7.20(m,2H),7.11(dd,J＝9.1,7.8Hz,1H),6.38(t,J＝3.81,2H),6.24(dd,J＝7.8,4.4Hz,1H),2.26(s,3H).13C NMR(75MHz,CDCl3)δ157.0(d,JC-F＝51.9),156.7,153.4,151.2(d,JC-F＝3.1),151.1,150.0,149.6,143.0,138.5(d,JC-F＝11.1),138.1,138.0,132.7,129.2,125.4,124.4(d,JC-F＝9.8),120.6(d,JC-F＝33.6),120.4,106.0(d,JC-F＝10.3),105.9,15.1.3-Fluoro-2H-[1,2'-bipyridyl]-2-one 1b (0.2 mmol), 2-methylthiophene 2a (0.24 mmol), [Cp * RhCl 2 ] 2 ( 5 mol%), AgSbF6 ( 25 mol%), Ag2O (0.2 mmol), pivalic acid (0.3 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 60°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ba was obtained by column chromatography with a yield of 66%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.49 (d, J=3.7 Hz, 1H), 7.73 (td, J=7.7, 1.9 Hz, 1H), 7.30-7.20 (m, 2H), 7.11 (dd, J=9.1, 7.8Hz, 1H), 6.38 (t, J=3.81, 2H), 6.24 (dd, J=7.8, 4.4Hz, 1H), 2.26 (s, 3H). 13 C NMR (75MHz, CDCl 3 )δ157.0(d, JCF =51.9),156.7,153.4,151.2(d, JCF =3.1),151.1,150.0,149.6,143.0,138.5(d, JCF =11.1),138.1,138.0,132.7 , 129.2, 125.4, 124.4 (d, J CF = 9.8), 120.6 (d, J CF = 33.6), 120.4, 106.0 (d, J CF = 10.3), 105.9, 15.1.
实施例3Example 3
在空气条件下，将3-氯-2H-[1,2'-联吡啶]-2-酮1c(0.2mmol)、2-甲基噻吩2a(0.3mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.1mmol)、三氟乙酸(0.3mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到50℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ca，产率为61％。1H NMR(400MHz,CDCl3)δ8.55(d,J＝4.8Hz,1H),7.79(td,J＝7.7,1.8Hz,1H),7.59(d,J＝7.6Hz,1H),7.35-7.29(m,2H),6.46(q,J＝3.8Hz,2H),6.36(d,J＝7.7Hz,1H),2.33(s,3H).13C NMR(75MHz,CDCl3)δ159.5,151.7,149.6,143.5,141.3,138.5,137.8,132.7,129.5,125.6,125.4,124.4,124.4,107.3,15.2.3-Chloro-2H-[1,2'-bipyridyl]-2-one 1c (0.2 mmol), 2-methylthiophene 2a (0.3 mmol), Cp * Rh(OAc) 2 ( 5 mol%), AgSbF6 ( 25 mol%), Ag2O (0.1 mmol), trifluoroacetic acid (0.3 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 50°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ca was obtained by column chromatography with a yield of 61%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.55 (d, J=4.8 Hz, 1H), 7.79 (td, J=7.7, 1.8 Hz, 1H), 7.59 (d, J=7.6 Hz, 1H), 7.35 -7.29(m, 2H), 6.46(q, J=3.8Hz, 2H), 6.36(d, J=7.7Hz, 1H), 2.33(s, 3H). 13 C NMR (75MHz, CDCl 3 )δ159. 5,151.7,149.6,143.5,141.3,138.5,137.8,132.7,129.5,125.6,125.4,124.4,124.4,107.3,15.2.
实施例4Example 4
在空气条件下，将3-溴-2H-[1,2'-联吡啶]-2-酮1d(0.2mmol)、2-甲基噻吩2a(0.6mmol)、[Cp*Rh(MeCN)2][SbF6]2(5mol％)、AgSbF6(25mol％)、Ag2O(0.2mmol)、特戊酸(0.4mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到50℃，反应时间经历6小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3da，产率为55％。1H NMR(400MHz,CDCl3)δ8.56(d,J＝4.1Hz,1H),7.80(t,J＝7.7Hz,2H),7.36-7.29(m,2H),6.49-6.45(m,2H),6.31(d,J＝7.6Hz,1H),2.34(s,3H).13C NMR(75MHz,CDCl3)δ159.5,151.9,149.6,143.5,142.1,141.7,138.5,132.7,129.5,125.6,124.4,115.4,107.8,15.2.Under air conditions, 3-bromo-2H-[1,2'-bipyridyl]-2-one 1d (0.2 mmol), 2-methylthiophene 2a (0.6 mmol), [Cp * Rh(MeCN) 2 ] [ SbF6 ] 2 (5 mol%), AgSbF6 ( 25 mol%), Ag2O (0.2 mmol), pivalic acid (0.4 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 50°C for a reaction time of 6 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3da was obtained by column chromatography with a yield of 55%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.56 (d, J=4.1 Hz, 1H), 7.80 (t, J=7.7 Hz, 2H), 7.36-7.29 (m, 2H), 6.49-6.45 (m, 2H), 6.31(d, J=7.6Hz, 1H), 2.34(s, 3H). 13 C NMR (75MHz, CDCl 3 )δ159.5, 151.9, 149.6, 143.5, 142.1, 141.7, 138.5, 132.7, 129.5, 125.6 ,124.4,115.4,107.8,15.2.
实施例5Example 5
在空气条件下，将3-(三氟甲基)-2H-[1,2'-联吡啶]-2-酮1e(0.2mmol)、2-甲基噻吩2a(0.6mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2CO3(0.2mmol)、特戊酸(0.3mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ea，产率为70％1H NMR(300MHz,CDCl3)δ8.49(d,J＝3.7Hz,1H),7.73(td,J＝7.7,1.9Hz,1H),7.30-7.20(m,2H),7.11(dd,J＝9.1,7.8Hz,1H),6.38(t,J＝3.81,2H),6.24(dd,J＝7.8,4.4Hz,1H),2.26(s,3H).13C NMR(75MHz,CDCl3)δ157.0(d,JC-F＝51.9),156.7,153.4,151.2(d,JC-F＝3.1),151.1,150.0,149.6,143.0,138.5(d,JC-F＝11.1),138.1,138.0,132.7,129.2,125.4,124.4(d,JC-F＝9.8),120.6(d,JC-F＝33.6),120.4,106.0(d,JC-F＝10.3),105.9,15.1.Under air conditions, 3-(trifluoromethyl)-2H-[1,2'-bipyridyl]-2-one 1e (0.2 mmol), 2-methylthiophene 2a (0.6 mmol), Cp * Rh (OAc) 2 (5 mol%), AgSbF6 ( 25 mol%), Ag2CO3 (0.2 mmol), pivalic acid (0.3 mmol), THF ( 3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ea was obtained by column chromatography with a yield of 70%. 1 H NMR (300 MHz, CDCl 3 ) δ8.49 (d, J=3.7 Hz, 1H), 7.73 (td, J= 7.7,1.9Hz,1H),7.30-7.20(m,2H),7.11(dd,J=9.1,7.8Hz,1H),6.38(t,J=3.81,2H),6.24(dd,J=7.8, 4.4Hz, 1H), 2.26 (s, 3H). 13 C NMR (75MHz, CDCl 3 ) δ 157.0 (d, J CF = 51.9), 156.7, 153.4, 151.2 (d, J CF = 3.1), 151.1, 150.0, 149.6, 143.0, 138.5 (d, J CF = 11.1), 138.1, 138.0, 132.7, 129.2, 125.4, 124.4 (d, J CF = 9.8), 120.6 (d, J CF = 33.6), 120.4, 106.0 ( d, J CF = 10.3), 105.9, 15.1.
实施例6Example 6
在空气条件下，将3-甲基-2H-[1,2'-联吡啶]-2-酮1f(0.2mmol)、2-甲基噻吩2a(0.3mmol)、[Cp*Rh(MeCN)2](5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、苯甲酸(0.4mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到60℃，反应时间经历7小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3fa，产率为62％1H NMR(300MHz,CDCl3)δ8.56(d,J＝3.6Hz,1H),7.76(td,J＝7.7,1.9Hz,1H),7.33-7.26(m,3H),6.42(t,J＝4.9Hz,2H),6.34(d,J＝7.0Hz,1H),2.32(s,3H),2.17(s,3H).13C NMR(75MHz,CDCl3)δ163.7,152.5,149.5,142.3,139.6,138.2,137.1,133.7,129.3,128.7,125.3,124.5,123.9,107.9,17.1,15.1.3-Methyl-2H-[1,2'-bipyridyl]-2-one 1f (0.2 mmol), 2-methylthiophene 2a (0.3 mmol), [Cp * Rh(MeCN) 2 ] (5 mol %), AgSbF 6 (25 mol %), Ag 2 O (0.3 mmol), benzoic acid (0.4 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 60°C and the reaction time was 7 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3fa was obtained by column chromatography with a yield of 62%. 1 H NMR (300 MHz, CDCl 3 ) δ8.56 (d, J=3.6 Hz, 1H), 7.76 (td, J= 7.7,1.9Hz,1H),7.33-7.26(m,3H),6.42(t,J=4.9Hz,2H),6.34(d,J=7.0Hz,1H),2.32(s,3H),2.17( s, 3H). 13 C NMR (75MHz, CDCl 3 )δ163.7, 152.5, 149.5, 142.3, 139.6, 138.2, 137.1, 133.7, 129.3, 128.7, 125.3, 124.5, 123.9, 107.9, 17.1, 15.1.
实施例7Example 7
在空气条件下，将2-(吡啶-2-基)异喹啉-1(2H)-酮1h(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、AgNO3(0.2mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ha，产率为66％。1H NMR(300MHz,CDCl3)δ8.57(s,1H),8.41(d,J＝8.1Hz,1H),7.78(td,J＝7.7,1.9Hz,1H),7.71-7.65(m,1H),7.56-7.46(m,2H),7.36-7.29(m,2H),6.75(s,1H),6.51(d,J＝3.6Hz,1H),6.45(dd,J＝3.6,1.1Hz,1H),2.36(s,3H).13C NMR(75MHz,CDCl3)δ163.2,152.5,149.4,142.0,138.1,136.8,136.2,134.4,133.0,128.7,128.2,127.1,126.2,125.4,125.3,124.9,123.7,108.6,15.2.2-(Pyridin-2-yl)isoquinolin-1(2H)-one 1h (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 ( 5 mol%), AgSbF6 (25 mol%), AgNO3 (0.2 mmol), pivalic acid (0.5 mmol), THF ( 3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ha was obtained by column chromatography with a yield of 66%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.57 (s, 1H), 8.41 (d, J=8.1 Hz, 1H), 7.78 (td, J=7.7, 1.9 Hz, 1H), 7.71-7.65 (m, 1H), 7.56-7.46(m, 2H), 7.36-7.29(m, 2H), 6.75(s, 1H), 6.51(d, J=3.6Hz, 1H), 6.45(dd, J=3.6, 1.1Hz) , 1H), 2.36(s, 3H). 13 C NMR(75MHz, CDCl 3 )δ163.2,152.5,149.4,142.0,138.1,136.8,136.2,134.4,133.0,128.7,128.2,127.1,126.2,125.4,125.3, 124.9, 123.7, 108.6, 15.2.
实施例8Example 8
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-氯噻吩2b(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ab，产率为72％。1H NMR(300MHz,CDCl3)δ8.56(d,J＝3.7Hz,1H),7.80(td,J＝7.7,1.9Hz,1H),7.43-7.29(m,3H),6.65(dd,J＝9.3,1.2Hz,1H),6.61(d,J＝4.0Hz,1H),6.51(d,J＝4.0Hz,1H),6.37(dd,J＝6.9,1.2Hz,1H).13C NMR(101MHz,CDCl3)δ163.1,151.6,149.7,141.1,139.8,138.6,134.3,132.8,128.5,126.2,124.5,124.4,121.1,108.6.N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-chlorothiophene 2b (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ab was obtained by column chromatography with a yield of 72%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.56 (d, J=3.7 Hz, 1H), 7.80 (td, J=7.7, 1.9 Hz, 1H), 7.43-7.29 (m, 3H), 6.65 (dd, 13C NMR (101MHz, CDCl 3 ) δ 163.1, 151.6, 149.7, 141.1, 139.8, 138.6, 134.3, 132.8, 128.5, 126.2, 124.5, 124.4, 121.1, 108.6.
实施例9Example 9
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-溴噻吩2c(0.6mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、AgOAc(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到60℃，反应时间经历8小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ac，产率为70％.1H NMR(300MHz,CDCl3)δ8.57-8.54(m,1H),7.82-7.77(m,1H),7.43-7.28(m,3H),6.75(dd,J＝4.0,0.9Hz,1H),6.65(d,J＝9.3Hz,1H),6.48(d,J＝3.9Hz,1H),6.37(d,J＝6.9Hz,1H).13C NMR(75MHz,CDCl3)δ163.1,151.6,149.7,141.0,139.7,138.6,137.2,129.9,129.4,124.5,124.4,121.2,115.3,108.6.N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-bromothiophene 2c (0.6 mmol), [Cp * RhCl 2 ] 2 (5 mol %), AgSbF 6 ( 25 mol%), AgOAc (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 60°C and the reaction time was over 8 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ac was obtained by column chromatography with a yield of 70%. 1 H NMR (300 MHz, CDCl 3 ) δ8.57-8.54 (m, 1H), 7.82-7.77 (m, 1H) ,7.43-7.28(m,3H),6.75(dd,J＝4.0,0.9Hz,1H),6.65(d,J＝9.3Hz,1H),6.48(d,J＝3.9Hz,1H),6.37( d, J=6.9Hz, 1H). 13 C NMR (75MHz, CDCl 3 ) δ 163.1, 151.6, 149.7, 141.0, 139.7, 138.6, 137.2, 129.9, 129.4, 124.5, 124.4, 121.2, 115.3, 108.6.
实施例10Example 10
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2,3-二溴噻吩2d(0.6mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、冰醋酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ad，产率为83％。1H NMR(300MHz,CDCl3)δ8.58-8.55(m,1H),7.82(td,J＝7.7,1.9Hz,1H),7.43-7.34(m,2H),7.32(d,J＝7.9Hz,1H),6.67(dd,J＝9.3,1.2Hz,1H),6.57(s,1H),6.36(dd,J＝6.9,1.2Hz,1H).13C NMR(75MHz,CDCl3)δ162.9,151.2,149.8,140.1,139.6,138.7,137.1,131.3,124.6,124.5,121.8,114.2,113.9,108.7.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2,3-dibromothiophene 2d (0.6 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF6 ( 25 mol%), Ag2O (0.3 mmol), glacial acetic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ad was obtained by column chromatography with a yield of 83%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.58-8.55 (m, 1H), 7.82 (td, J=7.7, 1.9 Hz, 1H), 7.43-7.34 (m, 2H), 7.32 (d, J=7.9 Hz, 1H), 6.67 (dd, J=9.3, 1.2Hz, 1H), 6.57 (s, 1H), 6.36 (dd, J=6.9, 1.2Hz, 1H). 13 C NMR (75MHz, CDCl 3 )δ162 .9,151.2,149.8,140.1,139.6,138.7,137.1,131.3,124.6,124.5,121.8,114.2,113.9,108.7.
实施例11Example 11
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-溴-3-甲基噻吩2e(0.3mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、Ag2CO3(0.2mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历9小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ae，产率为66％。1H NMR(300MHz,CDCl3)δ8.50(d,J＝3.2Hz,1H),7.74(td,J＝7.8,1.9Hz,1H),7.36-7.21(m,3H),6.58(d,J＝9.2Hz,1H),6.39(s,1H),6.30(d,J＝6.7Hz,1H),1.93(s,3H).13C NMR(75MHz,CDCl3)δ163.2,151.6,149.7,141.5,139.8,138.6,137.2,135.1,130.9,124.6,124.4,120.8,112.8,108.3,15.1.Under air, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-bromo-3-methylthiophene 2e (0.3 mmol), [Cp * RhCl 2 ] 2 (5 mol% ), AgSbF 6 (25 mol%), Ag 2 CO 3 (0.2 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was 9 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ae was obtained by column chromatography in a yield of 66%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.50 (d, J=3.2 Hz, 1H), 7.74 (td, J=7.8, 1.9 Hz, 1H), 7.36-7.21 (m, 3H), 6.58 (d, J=9.2Hz, 1H), 6.39(s, 1H), 6.30(d, J=6.7Hz, 1H), 1.93(s, 3H). 13 C NMR (75MHz, CDCl 3 ) δ 163.2, 151.6, 149.7, 141.5 ,139.8,138.6,137.2,135.1,130.9,124.6,124.4,120.8,112.8,108.3,15.1.
实施例12Example 12
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-氯-3-甲基噻吩2f(0.6mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、AgNO3(0.2mmol)、苯甲酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3af，产率为64％。1H NMR(300MHz,CDCl3)δ8.58-8.55(m,1H),7.80(td,J＝7.7,1.9Hz,1H),7.42-7.29(m,3H),6.63(dd,J＝9.3,1.2Hz,1H),6.46(s,1H),6.36(dd,J＝6.9,1.2Hz,1H),1.99(s,3H).13C NMR(75MHz,CDCl3)δ163.2,151.7,149.7,141.5,139.8,138.6,134.4,132.0,130.6,128.1,124.6,124.4,120.9,108.3,13.4.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-chloro-3-methylthiophene 2f (0.6 mmol), Cp * Rh(OAc) 2 (5 mol% ), AgSbF 6 (25 mol%), AgNO 3 (0.2 mmol), benzoic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3af was obtained by column chromatography in a yield of 64%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.58-8.55 (m, 1H), 7.80 (td, J=7.7, 1.9 Hz, 1H), 7.42-7.29 (m, 3H), 6.63 (dd, J=9.3 , 1.2Hz, 1H), 6.46(s, 1H), 6.36(dd, J=6.9, 1.2Hz, 1H), 1.99(s, 3H). 13 C NMR (75MHz, CDCl 3 )δ163.2, 151.7, 149.7, 141.5, 139.8, 138.6, 134.4, 132.0, 130.6, 128.1, 124.6, 124.4, 120.9, 108.3, 13.4.
实施例13Example 13
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-氰基噻吩2g(0.6mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、Ag2CO3(0.2mmol)、冰醋酸(0.4mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ag，产率为75％。1H NMR(400MHz,CDCl3)δ8.52(s,1H),7.83(t,J＝7.5Hz,1H),7.45(dd,J＝9.4,6.8Hz,1H),7.36(t,J＝7.6Hz,2H),7.31(d,J＝3.9Hz,1H),6.77-6.73(m,2H),6.45(d,J＝6.8Hz,1H).13C NMR(75MHz,CDCl3)δ162.7,151.1,149.8,142.8,139.5,138.6,136.8,128.8,124.6,122.7,113.3,111.6,109.6.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-cyanothiophene 2 g (0.6 mmol), [Cp * RhCl 2 ] 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2CO3 (0.2 mmol), glacial acetic acid (0.4 mmol), THF ( 3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ag was obtained by column chromatography with a yield of 75%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.52 (s, 1H), 7.83 (t, J=7.5 Hz, 1H), 7.45 (dd, J=9.4, 6.8 Hz, 1H), 7.36 (t, J= 7.6Hz, 2H), 7.31 (d, J=3.9Hz, 1H), 6.77-6.73 (m, 2H), 6.45 (d, J=6.8Hz, 1H). 13 C NMR (75MHz, CDCl 3 )δ162. 7,151.1,149.8,142.8,139.5,138.6,136.8,128.8,124.6,122.7,113.3,111.6,109.6.
实施例14Example 14
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-乙酰基噻吩2h(0.4mmol)、[Cp*Rh(MeCN)2][SbF6]2(5mol％)、AgSbF6(25mol％)、AgOAc(0.3mmol)、三氟乙酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历8小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ah，产率为46％。1H NMR(400MHz,CDCl3)δ8.51(d,J＝4.6Hz,1H),7.80(td,J＝7.7,1.9Hz,1H),7.44(dd,J＝9.3,6.9Hz,1H),7.36-7.30(m,3H),6.72-6.70(m,2H),6.46(d,J＝6.9Hz,1H),2.45(s,3H).13C NMR(75MHz,CDCl3)δ190.5,163.0,151.4,149.6,145.5,143.6,141.0,139.6,138.5,131.7,129.6,124.6,124.3,122.0,109.2,26.7.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-acetylthiophene 2h (0.4 mmol), [Cp * Rh(MeCN) 2 ][ SbF6 ] 2 (5 mol %), AgSbF6 (25 mol %), AgOAc (0.3 mmol), trifluoroacetic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was 8 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ah was obtained by column chromatography with a yield of 46%. 1 H NMR (400MHz, CDCl 3 ) δ 8.51 (d, J=4.6Hz, 1H), 7.80 (td, J=7.7, 1.9Hz, 1H), 7.44 (dd, J=9.3, 6.9Hz, 1H) , 7.36-7.30(m, 3H), 6.72-6.70(m, 2H), 6.46(d, J=6.9Hz, 1H), 2.45(s, 3H). 13 C NMR(75MHz, CDCl 3 )δ190.5,163.0 ,151.4,149.6,145.5,143.6,141.0,139.6,138.5,131.7,129.6,124.6,124.3,122.0,109.2,26.7.
实施例15Example 15
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-噻吩甲酸甲酯2i(0.6mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、冰醋酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ai，产率为45％。1H NMR(300MHz,CDCl3)δ8.52-8.50(m,1H),7.78(td,J＝7.8,1.9Hz,1H),7.46-7.40(m,2H),7.35-7.28(m,2H),6.70(dd,J＝9.3,1.2Hz,1H),6.66(d,J＝4.0Hz,1H),6.44(dd,J＝6.9,1.2Hz,1H),3.81(s,3H).13C NMR(75MHz,CDCl3)δ163.0,162.0,151.5,149.7,142.2,140.9,139.6,138.5,134.9,132.9,129.3,124.5,124.3,121.9,109.2,52.4.N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), methyl 2-thiophenecarboxylate 2i (0.6 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF under air condition 6 ( 25 mol%), Ag2O (0.3 mmol), glacial acetic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ai was obtained by column chromatography with a yield of 45%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.52-8.50 (m, 1H), 7.78 (td, J=7.8, 1.9 Hz, 1H), 7.46-7.40 (m, 2H), 7.35-7.28 (m, 2H) ), 6.70(dd, J=9.3, 1.2Hz, 1H), 6.66(d, J=4.0Hz, 1H), 6.44(dd, J=6.9, 1.2Hz, 1H), 3.81(s, 3H). 13 C NMR (75MHz, CDCl 3 ) δ 163.0, 162.0, 151.5, 149.7, 142.2, 140.9, 139.6, 138.5, 134.9, 132.9, 129.3, 124.5, 124.3, 121.9, 109.2, 52.4.
实施例16Example 16
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-苯基噻吩2j(0.6mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、Ag2O(0.2mmol)、冰醋酸(0.4mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到50℃，反应时间经历10小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aj，产率为68％。1H NMR(300MHz,CDCl3)δ8.58(dd,J＝4.8,1.1Hz,1H),7.80(td,J＝7.7,1.9Hz,1H),7.47-7.41(m,3H),7.37-7.27(m,5H),6.99(d,J＝3.9Hz,1H),6.67(dd,J＝9.3,1.2Hz,1H),6.63(d,J＝3.9Hz,1H),6.49(dd,J＝7.0,1.2Hz,1H).13C NMR(75MHz,CDCl3)δ163.4,152.0,149.7,146.8,142.0,139.9,138.5,134.8,133.2,130.0,129.01,128.2,125.7,124.6,124.2,123.0,120.6,108.4.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-phenylthiophene 2j (0.6 mmol), [Cp * RhCl 2 ] 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.2 mmol), glacial acetic acid (0.4 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 50°C and the reaction time was over 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aj was obtained by column chromatography with a yield of 68%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.58 (dd, J=4.8, 1.1 Hz, 1H), 7.80 (td, J=7.7, 1.9 Hz, 1H), 7.47-7.41 (m, 3H), 7.37- 7.27(m,5H),6.99(d,J=3.9Hz,1H),6.67(dd,J=9.3,1.2Hz,1H),6.63(d,J=3.9Hz,1H),6.49(dd,J =7.0, 1.2Hz, 1H). 13 C NMR (75MHz, CDCl 3 )δ163.4, 152.0, 149.7, 146.8, 142.0, 139.9, 138.5, 134.8, 133.2, 130.0, 129.01, 128.2, 125.7, 124.6, 124.2, 123.0, 120.6, 108.4.
实施例17Example 17
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、苯并噻吩2k(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2CO3(0.2mmol)、三氟乙酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到70℃，反应时间经历8小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3ak，产率为65％。1H NMR(400MHz,CDCl3)δ8.52(d,J＝3.1Hz,1H),7.77(td,J＝7.7,1.9Hz,1H),7.67(t,J＝5.6Hz,1H),7.61(t,J＝3.6Hz,1H),7.46(dd,J＝9.3,6.9Hz,1H),7.38(d,J＝7.9Hz,1H),7.31-7.26(m,3H),6.99(s,1H),6.71(d,J＝9.3Hz,1H),6.53(d,J＝6.8Hz,1H).13C NMR(101MHz,CDCl3)δ163.2,151.7,149.6,142.2,140.4,139.7,138.8,138.4,136.0,126.0,125.3,124.7,124.6,124.2,124.2,121.9,121.4,109.4.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), benzothiophene 2k (0.4 mmol), Cp * Rh(OAc) 2 (5 mol %), AgSbF 6 (25 mol %), Ag2CO3 ( 0.2 mmol), trifluoroacetic acid (0.5 mmol), THF ( 3 mL) were added to a Schlenk reaction tube and sealed. Heated to 70°C and the reaction time was 8 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ak was obtained by column chromatography with a yield of 65%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.52 (d, J=3.1 Hz, 1H), 7.77 (td, J=7.7, 1.9 Hz, 1H), 7.67 (t, J=5.6 Hz, 1H), 7.61 (t, J=3.6Hz, 1H), 7.46(dd, J=9.3, 6.9Hz, 1H), 7.38(d, J=7.9Hz, 1H), 7.31-7.26(m, 3H), 6.99(s, 1H), 6.71(d, J=9.3Hz, 1H), 6.53(d, J=6.8Hz, 1H). 13 C NMR (101MHz, CDCl 3 )δ163.2, 151.7, 149.6, 142.2, 140.4, 139.7, 138.8, 138.4, 136.0, 126.0, 125.3, 124.7, 124.6, 124.2, 124.2, 121.9, 121.4, 109.4.
实施例18Example 18
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、3-甲基噻吩2l(0.2mmol)、[Cp*RhCl2]2(5mol％)、AgSbF6(25mol％)、AgNO3(0.3mmol)、苯甲酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历9小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3al，产率为67％。1H NMR(300MHz,CDCl3)δ8.56-8.54(m,1H),7.77(td,J＝7.7,1.9Hz,1H),7.41(dd,J＝9.3,7.0Hz,1H),7.33-7.29(m,2H),6.78(t,J＝1.2Hz,1H),6.64(dd,J＝9.3,1.2Hz,1H),6.53(d,J＝1.5Hz,1H),6.42(dd,J＝7.0,1.2Hz,1H),2.10(s,0.11H),2.06(s,3H),2.03(s,0.20H).13C NMR(75MHz,CDCl3)δ163.4,152.0,149.5,142.4,139.9,138.3,137.5,135.6,131.4,124.6,124.1,123.6,120.4,108.3,15.5.Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 3-methylthiophene 2l (0.2 mmol), [Cp * RhCl 2 ] 2 (5 mol%), AgSbF 6 (25 mol%), AgNO3 (0.3 mmol), benzoic acid (0.5 mmol), THF ( 3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was 9 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3a1 was obtained by column chromatography with a yield of 67%. 1 H NMR (300 MHz, CDCl 3 ) δ 8.56-8.54 (m, 1H), 7.77 (td, J=7.7, 1.9 Hz, 1H), 7.41 (dd, J=9.3, 7.0 Hz, 1H), 7.33- 7.29(m,2H),6.78(t,J=1.2Hz,1H),6.64(dd,J=9.3,1.2Hz,1H),6.53(d,J=1.5Hz,1H),6.42(dd,J =7.0, 1.2Hz, 1H), 2.10(s, 0.11H), 2.06(s, 3H), 2.03(s, 0.20H). 13 C NMR (75MHz, CDCl 3 ) δ 163.4, 152.0, 149.5, 142.4, 139.9 ,138.3,137.5,135.6,131.4,124.6,124.1,123.6,120.4,108.3,15.5.
对照例1Comparative Example 1
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到100℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率仅为55％。升高温度反而对产率不利。Under air condition, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 100°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of only 55%. Elevated temperature is detrimental to yield.
对照例2Comparative Example 2
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，1,4-二氧六环(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率为33％。1,4-二氧六环不是反应的良溶剂。Under air condition, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), 1,4-dioxane (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 33%. 1,4-Dioxane is not a good solvent for the reaction.
对照例3Comparative Example 3
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，乙腈(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。经TLC检测，只有痕量产物生成。Under air condition, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), acetonitrile (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. Only trace amounts of product were produced by TLC.
对照例4Comparative Example 4
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，二氯乙烷(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率为43％。反应在二氯乙烷溶剂中反应较差。Under air condition, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), dichloroethane (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 43%. The reaction reacted poorly in dichloroethane solvent.
对照例5Comparative Example 5
在空气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率为45％。催化剂助剂有利于提高产物的收率。Under air conditions, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), Ag 2 O (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 45%. The catalyst promoter is beneficial to improve the yield of the product.
对照例6Comparative Example 6
在氮气条件下，将N-(2-吡啶基)-2-吡啶酮1a(0.2mmol)、2-甲基噻吩2a(0.4mmol)、Cp*Rh(OAc)2(5mol％)、AgSbF6(25mol％)、Ag2O(0.3mmol)、特戊酸(0.5mmol)，THF(3mL)加入到Schlenk反应管中，密封。加热到80℃，反应时间经历12小时。反应结束后减压除溶剂，柱色谱分离得到目标产物3aa，产率为70％。惰性气体保护，并不会提升产率。Under nitrogen, N-(2-pyridyl)-2-pyridone 1a (0.2 mmol), 2-methylthiophene 2a (0.4 mmol), Cp * Rh(OAc) 2 (5 mol%), AgSbF 6 ( 25 mol%), Ag2O (0.3 mmol), pivalic acid (0.5 mmol), THF (3 mL) were added to a Schlenk reaction tube and sealed. Heated to 80°C and the reaction time was over 12 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 70%. Inert gas protection does not improve yields.
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