CN105693778A - N-methoxyl formamide-orientated method for synthesizing ferrocene and pyridone derivative - Google Patents
N-methoxyl formamide-orientated method for synthesizing ferrocene and pyridone derivative Download PDFInfo
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Abstract
The invention discloses an N-methoxyl formamide-orientated method for synthesizing a ferrocene and pyridone derivative. According to the method, under the conditions that palladium acetate is taken as a catalyst, copper acetate is taken as a catalyst promoter and quaternary ammonium salt and alkali are taken as additives, an N-methoxyl ferrocene and [c] pyridine-2(1H)-ketone derivative is obtained by carrying out a cyclization reaction on N-methoxyl ferrocene formamide and alkyne. The method adopts an N-methoxyl formamide-orientated carbon-hydrogen bond and nitrogen-hydrogen bond double-activation reaction to synthesize the N-methoxyl ferrocene and [c] pyridine-2(1H)-ketone derivative in one step. The organometallic condensed heterocyclic compounds are unique in structure, thus being hard to prepare by a conventional method; the method provided by the invention has the characteristics of being easy in obtaining of raw materials and mild in reaction conditions, not needing the protection of inert gas, being high in synthetic yield, and the like; therefore, a new way is provided for the synthesis of novel ferrocene and heterocyclic compounds, and the method has an important significance for expanding the application of the compounds in the fields such as medicinal chemistry, material chemistry, catalysts and the like.
Description
Technical field
The present invention relates to a kind of ferrocene pyridinone fused heterocyclic compound and synthetic method thereof, be specifically related to a kind of N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant and synthetic method thereof。
Background technology
Heterocyclic compound is that a class contains heteroatomic cyclic organic compounds, majority has important biological activity, various heterocycle structures be widely present in the chemicals molecular structure such as natural product and medicine, Insecticides (tech) & Herbicides (tech), dyestuff ((a) MichaelJ.P.Nat.Prod.Rep., 2008,25,139. (b) MichaelJ.P.Nat.Prod.Rep., 2007,24,191. (c) MichaelJ.P.Nat.Prod.Rep., 2005,22,603.)。Therefore, the synthetic methodology research about the research of heterocyclic compound, particularly fused heterocyclic compound gains great popularity always。
Ferrocene and its derivative is a very important metallo-organic compound of class, and its core skeleton frequently occurs on ((a) Hayashi, T. in various new catalyst, new material and new drug molecular structure；Togni, A.Eds.Ferrocenes；VCH:Weinheim, Germany, 1995. (b) Togni, A.；Haltermann, R.L.Eds.Metallocenes；VCH:Weinheim, Germany, 1998.)。People study discovery, in some bioactive molecule, introduce ferrocene structure and can significantly improve its biological activity ((a) Top, S.；Tang, J.；Vessieres, A.；Carrez, D.；Provot, C.；Jaouen, G.Chem.Commun., 1996,955. (b) Hillard, E.；Vessieres, A.；Thouin, L.；Jaouen, G.；Amatore, C.Angew.Chem.Int.Ed., 2006,45,285. (c) Hamels, D.；Dansette, P.M.；Hillard, E.A.；Top, S.；Vessieres, A.；Herson, P.；Jaouen, G.；Mansuy, D.Angew.Chem.Int.Ed., 2009,48,9124. (d) Monserrat, J.P.；Chabot, G.G.；Hamon, L.；Quentin, L.；Scherman, D.；Jaouen, G.；Hillard, E.A.Chem.Commun., 2010,46,5145. (e) Ornelas, C.NewJ.Chem., 2011,35,1973. (f) Kilpin, K.J.；Dyson, P.J.Chem.Sci., 2013,4,1410.), therefore drug modification and new drug development are had great importance。But, at present ferrocene frame having ferrocene frame being introduced bioactive molecule, the method for especially various heterocyclic molecular is also very limited, reacts mainly by acyl group, lithio etc., and its Atom economy is not high, severe reaction conditions, and synthesis step is complicated。
In recent years, along with metal catalytic various carbon-hydrogen link priming reactions heterocyclic compound synthesize in application, expanded synthetic method ((a) Luis, A. of Ferrocene Derivatives；L ó pez, E.DaltonTrans., 2015,44,10128. (b) Xie, W.C.；Li, B.；Xu, S.S.；Song, H.B.；Wang, B.Q.Organometallics, 2014,33,2138. (c) Wang Baiquan, Xie Wucheng, Xu Shansheng, Li Bin .CN103788137A, 2014-05-14)。Wherein, in the king one hundred disclosed patent (CN103788137A) of congruence although in describe the carbon-hydrogen link with N-alkyl formamides and the N-aryl benzene ring substitution group of ester group, methoxyl group and various halogen substiuted (these aryl include) Methanamide guiding and nitrogen-hydrogen bond priming reaction, serial ferrocene Hete rocyclic derivatives has been synthesized when 90-100 DEG C, but the compound of its synthesis is not easily further converted to other N-ferrocene replaced Hete rocyclic derivatives, has certain limitation in application。And have no report with N-methoxymethylamide (MeONHCO-) guiding synthesis N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds。
Summary of the invention
It is contemplated that for the deficiency existed in above-mentioned technical Analysis, a kind of novel ferrocene the synthetic method of pyridinone fused heterocyclic compound are provided, purpose is with N-methoxyl group ferrocene formamide and various asymmetric alkynes for primary raw material, the carbon-hydrogen link led by N-methoxymethylamide and the bis-activated reaction of nitrogen-hydrogen bond, a step efficiently synthesizes N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant。The method does not need inert gas shielding, reaction condition Schweinfurt green gentle, catalytic amount (1～5mol%) significantly accelerated to react, productivity is high。N-methoxyl group ferrocene also [c] pyridine-2 (1H) the-one derivant structure of preparation is unique, containing methoxyl group on its pyridone nitrogen-atoms, it is prone to, by demethoxylation derivatization again, expand ferrocene the range of application of pyridinone fused heterocyclic compound further。
The present invention is by the following technical solutions:
The first aspect of the invention, the present invention provides a kind of N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds, shown in its chemical constitution such as formula (I):
(I) in formula: R, R, ' for aliphatic substitution or aromatic substituents, R, R ' can be identical, it is also possible to different。Me represents CH3。
The second aspect of the invention, the present invention provides the synthetic method of a kind of N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds, comprise the following steps: with N-methoxymethylamide for guiding base, with palladium be catalyst, Schweinfurt green be promoter, quaternary ammonium salt and alkali for additive when, in reaction dissolvent, N-methoxyl group ferrocene formamide and alkynes carry out cyclization, generate N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds。
Further, after N-methoxyl group ferrocene formamide and alkynes carry out the mixture that cyclization generates containing target compound, purified obtain N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds。
Concrete method of purification is: added water by the mixture containing target compound, and with organic solvent extraction, organic facies is scrubbed, dried, organic solvent is evaporated off and obtains crude product；Crude product obtains N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds through column chromatographic isolation and purification。
More specifically method of purification is: is added water by the mixture containing target compound, is then extracted with ethyl acetate, and extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material；Crude product, through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate and petroleum ether), finally obtains N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds。
N-methoxyl group ferrocene formamide used in the present invention, various alkynes, palladium, Schweinfurt green, quaternary ammonium salt and alkali are common chemicals or the self-control of reference literature method, and various solvents used are common chemicals, directly use after Non-aqueous processing。
The present invention adopts following reaction equation to represent:
Alkynes used in the present invention, structure isIncluding diaryl acetylene and alkylaryl acetylene; wherein R, R in diaryl acetylene structure ' can be identical; can also be different, aryl can be phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, to cyano-phenyl, to Fonnylphenyl, ferrocenyl, phenylacetylene base；Alkyl in alkylaryl acetylene structure includes propyl group, butyl, and aryl is identical with diaryl acetylene。
Preferably, in the present invention, alkynes mole dosage is 1～3 times of N-methoxyl group ferrocene formamide。
Palladium used in the present invention is catalyst, it is preferred that the mole dosage of described palladium is the 5～20% of N-methoxyl group ferrocene formamide。
Schweinfurt green used in the present invention is that promoter is not (because of under having Schweinfurt green existent condition, reaction still can be smoothed out, simply response speed is relatively slow, and response speed after adding a small amount of Schweinfurt green, can be significantly improved, respectively referring to embodiment 1 and embodiment 2), preferably, the mole dosage of described Schweinfurt green is the 1～5% of N-methoxyl group ferrocene formamide。
Quaternary ammonium salt used in the present invention is any one in tetrabutyl ammonium bromide (TBAB), tetrabutylammonium iodide (TBAI), cetyl trimethylammonium bromide (CTAB), preferably, the mole dosage of described quaternary ammonium salt is the 10～50% of N-methoxyl group ferrocene formamide。
Alkali used in the present invention is one or more combinations in sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium acetate, it is preferred that the mole dosage of described alkali is 1～3 times of N-methoxyl group ferrocene formamide。
Reaction dissolvent used in the present invention is one or more combinations in acetonitrile, oxolane, methanol, butanone, toluene, it is preferred that the consumption of described reaction dissolvent is 10～50 times of N-methoxyl group ferrocene formamide weight。
Reaction in the present invention is implemented in atmosphere, it is not necessary to inert gas shielding, and the reaction temperature of optimization is 30～80 DEG C, and the response time is 1～24 hour。Method provided by the present invention is easy and simple to handle, has efficiently synthesized N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant under mild conditions。
In N-methoxyl group ferrocene formamide structure used in the present invention, N-methoxymethylamide group (MeONHCO-) is carbon-hydrogen link activation guiding base, is not built-in oxidant, because the methoxyl group on pyridone nitrogen-atoms in the reaction product is not taken off。
The third aspect of the invention, the N-methoxyl group ferrocene of the present invention also [c] pyridine-2 (1H)-one compounds structure is unique, containing methoxyl group on its pyridone nitrogen-atoms, readily removed methoxyl group (referring to embodiment 14), achieve derivatization again, expand such ferrocene the range of application of pyridone fused heterocyclic compound further。
The beneficial effects of the present invention is:
(1) the N-methoxyl group ferrocene provided in the present invention [c] pyridine-2 (1H)-one derivant are compared with relevant ferrocene heterocycle compound, chemically structure, methoxyl group is contained at pyridone nitrogen-atoms, chemical constitution is unique, does not find that ferrocene pyridine compounds contain methoxyl group at pyridone nitrogen-atoms at present in the prior art。Owing to the pyridone nitrogen-atoms of N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant being connected with methoxyl group, easily by demethoxylation derivatization again, provide a kind of new approaches for synthesizing more novel compound containing ferrocene pyridone structure；Further, the N-methoxyl group ferrocene provided in the present invention [c] pyridine-2 (1H)-one derivant adopt prior art to be difficult to synthesize。Therefore, the technology provided in the present invention is prepare ferrocene and pyridine compounds provides important basis。
(2) also [c] pyridine-2 (1H) the-one compounds synthetic method of the N-methoxyl group ferrocene in the present invention, adopt carbon-hydrogen link and the bis-activated reaction of nitrogen-hydrogen bond of N-methoxymethylamide guiding, efficiently synthesize N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant。The present invention it have been investigated that, when with N-methoxymethylamide for guiding base, with palladium be catalyst, Schweinfurt green be promoter, quaternary ammonium salt and alkali for additive when, N-methoxyl group ferrocene formamide and alkynes carry out cyclization, owing to selecting the particularity of substrate, whole reaction is had material impact, causes that the technology of the present invention is different from existing inventive technique (CN103788137A)。It is embodied in: in N-methoxyl group ferrocene formamide structure, N-methoxymethylamide group (MeONHCO-) is carbon-hydrogen link activation guiding base, it it not built-in oxidant, methoxyl group on cause pyridone nitrogen-atoms in the reaction product is not taken off (generally, in some carbon-hydrogen link priming reactions, N-methoxymethylamide group (MeONHCO-) serves not only as guiding base, and serve as built-in oxidant, when generating respective compound, methoxyl group can remove therewith)；Schweinfurt green is as promoter in the technology of the present invention, and a small amount of Schweinfurt green can significantly improve response speed, and under not having Schweinfurt green existent condition, reaction still can be smoothed out, and simply response speed is relatively slow。
(3) synthetic method provided by the invention, have raw material be easy to get, without inert gas shielding, easy and simple to handle, reaction condition is gentle, synthetic yield high。The organic fused heterocyclic compound structure of this metalloid is unique, conventional method is adopted to be difficult to prepare, this synthesis being Ferrocene Derivatives provides new way, the particularly readily removed derivatization again of the methoxyl group on pyridone nitrogen-atoms in its structure, to expanding, its application in fields such as pharmaceutical chemistry, materials chemistry, catalyst is significant。
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention being expanded on further, embodiments of the invention are merely to illustrate technical scheme, rather than limit the scope of the present invention。
Embodiment 1:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), dibenzenyl (0.1424g, 0.8mmol), palladium (0.0100g, 0.044mmol), sodium acetate (0.0410g, 0.5mmol), CTAB (0.0292g, 0.08mmol) with the mixture of toluene (2mL), react 12 hours in 65 DEG C。Reactant mixture is cooled to room temperature, adds 5mL water, is then extracted with ethyl acetate, and extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) obtaining red solid, N-methoxyl group-5,6-diphenyl ferrocene is [c] pyridine-2 (1H)-one also, productivity 92%, m.p.177 DEG C (dec.)。
HR-MS(ESI)(m/z):Calcd.forC26H21FeNO2[M]+435.0922,Found:435.0921.
1HNMR(300MHz,CDCl3): δ 7.24-7.21 (m, 10H), 5.32 (d, 1H, J=2.4Hz), 4.56 (d, 1H, J=2.1Hz), 4.36 (t, 1H, J=2.7Hz), 4.14 (s, 5H), 3.62 (s, 3H)。
Embodiment 2:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), dibenzenyl (0.1424g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 8 hours in 65 DEG C。Reactant mixture is cooled to room temperature, adds 5mL water, is then extracted with ethyl acetate, and extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) obtaining red solid, N-methoxyl group-5,6-diphenyl ferrocene is [c] pyridine-2 (1H)-one also, productivity 93%, m.p.177 DEG C (dec.)。
HR-MS(ESI)(m/z):Calcd.forC26H21FeNO2[M]+435.0922,Found:435.0921.
1HNMR(300MHz,CDCl3): δ 7.24-7.21 (m, 10H), 5.32 (d, 1H, J=2.4Hz), 4.56 (d, 1H, J=2.1Hz), 4.36 (t, 1H, J=2.7Hz), 4.14 (s, 5H), 3.62 (s, 3H)。
Embodiment 3:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-phenyl-2-(4-nitrobenzophenone) acetylene (0.1785g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and acetonitrile (2mL), react 7 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) dark red solid, N-methoxyl group-6-phenyl-5-(4-nitrobenzophenone) ferrocene also [c] pyridine-2 (1H)-one, productivity 98%, m.p.165 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC26H20FeN2O4[M+H]+481.0851,Found:481.0974.
1HNMR(300MHz,CDCl3): δ 8.11 (d, 2H, J=8.4Hz), 7.43-7.17 (m, 7H), 5.35 (s, 1H), 4.54 (d, 1H, J=12.0Hz), 4.42 (s, 1H), 4.16 (s, 5H), 3.63 (s, 3H)。
Embodiment 4:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-phenyl-2-(4-cyano-phenyl) acetylene (0.1625g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 6 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.4) orange solids, N-methoxyl group-6-phenyl-5-(4-cyano-phenyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 93%, m.p.186 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC27H20FeN2O2[M]+460.0874,Found:460.0857.
1HNMR(300MHz,CDCl3): δ 7.53 (d, 2H, J=8.1Hz), 7.36-7.26 (m, 5H), 7.16-7.14 (m, 2H), 5.34 (s, 1H), 4.55 (s, 1H), 4.41 (s, 1H), 4.14 (s, 5H), 3.62 (s, 3H)。
Embodiment 5:
By N-methoxyl group ferrocene formamide (0.1036g; 0.4mmol), 1-phenyl-2-(4-Fonnylphenyl) acetylene (0.1649g; 0.8mmol), palladium (0.0100g; 0.044mmol), Schweinfurt green (0.0020g; 0.011mmol), potassium dihydrogen phosphate (0.0680g; 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 8 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.4) red solid, N-methoxyl group-6-phenyl-5-(4-Fonnylphenyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 90%, m.p.160 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC27H21FeNO3[M+Na]+486.0769,Found:486.0798.
1HNMR(300MHz,CDCl3): δ 9.99 (s, 1H), 7.76 (d, 2H, J=7.5Hz), 7.44-7.39 (m, 2H), 7.29-7.17 (m, 5H), 5.34 (t, 1H, J=2.4Hz), 4.57 (d, 1H, J=2.7Hz), 4.40 (t, 1H, J=2.7Hz), 4.16 (s, 5H), 3.62 (s, 3H)。
Embodiment 6:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-phenyl-2-(4-methoxyphenyl) acetylene (0.1665g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 13 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.4) red solid is obtained, N-methoxyl group-6-phenyl-5-(4-methoxyphenyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 82%, m.p.141-142 DEG C。
HR-MS(ESI)(m/z):Calcd.forC27H23FeNO3[M+H]+466.1106,Found:466.1106.
1HNMR(300MHz,CDCl3): δ 7.29-7.14 (m, 7H), 6.76 (d, 2H, J=8.4Hz), 5.31 (d, 1H, J=2.4Hz), 4.55 (d, 1H, J=2.4Hz), 4.35 (t, 1H, J=2.7Hz), 4.13 (s, 5H), 3.79 (s, 3H), 3.61 (s, 3H)。
Embodiment 7:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-phenyl pentyne (0.1153g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 18 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.6) red solid is obtained, N-methoxyl group-5-n-pro-pyl-6-diphenylphosphino ferrocene also [c] pyridine-2 (1H)-one, productivity 73%, m.p.125-127 DEG C。
HR-MS(ESI)(m/z):Calcd.forC23H23FeNO2[M]+402.1156,Found:402.1135.
1HNMR(300MHz,CDCl3): δ 7.47-7.43 (m, 3H), 7.36-7.32 (m, 2H), 5.25 (t, 1H, J=3.0Hz), 4.74 (d, 1H, J=2.4Hz), 4.39 (d, 1H, J=2.7Hz), 4.09 (s, 5H), 3.62 (s, 3H), 2.34-2.20 (m, 2H), 1.70-1.60 (m, 2H), 0.86 (t, 3H, J=7.5Hz)。
Embodiment 8:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-(4-nitrobenzophenone) pentyne (0.1513g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 13.5 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) red solid, N-methoxyl group-5-n-pro-pyl-6-(4-nitrobenzophenone) ferrocene also [c] pyridine-2 (1H)-one, productivity 83%, m.p.166 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC23H22FeN2O4[M+Na]+469.0827,Found:469.0842.
1HNMR(300MHz,CDCl3): δ 7.77 (t, 2H, J=6.2Hz), 7.49 (d, 2H, J=7.8Hz), 5.28 (d, 1H, J=3.0Hz), 4.77 (d, 1H, J=2.7Hz), 4.43 (t, 1H, J=2.6Hz), 4.10 (s, 5H), 3.62 (s, 3H), 2.35-2.17 (m, 2H), 1.73-1.58 (m, 2H), 0.88 (t, 3H, J=7.2Hz)。
Embodiment 9:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-(4-cyano-phenyl) pentyne (0.1353g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 20 hours in 60 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) yellowish red color solid is obtained, N-methoxyl group-5-n-pro-pyl-6-(4-cyano-phenyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 72%, m.p.171-172 DEG C。
HR-MS(ESI)(m/z):Calcd.forC24H22FeN2O2[M+H]+427.1109,Found:427.1109.
1HNMR(300MHz,CDCl3): δ 8.34 (d, 2H, J=8.1Hz), 7.55 (d, 2H, J=7.8Hz), 5.29 (d, 1H, J=2.7Hz), 4.78 (d, 1H, J=2.7Hz), 4.44 (t, 1H, J=2.9Hz), 4.11 (s, 5H), 3.62 (s, 3H), 2.39-2.15 (m, 2H), 1.80-1.55 (m, 2H), 0.88 (t, 3H, J=7.3Hz)。
Embodiment 10:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-(4-methoxyphenyl) pentyne (0.1393g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 12 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.4) red solid is obtained, N-methoxyl group-5-n-pro-pyl-6-(4-methoxyphenyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 70%, m.p.156-157 DEG C。
HR-MS(ESI)(m/z):Calcd.forC24H25FeNO3[M+H]+432.1262,Found:432.1247.
1HNMR(300MHz,CDCl3): δ 7.26 (t, 2H, J=6.3Hz), 6.97 (t, 2H, J=6.2Hz), 5.24 (t, 1H, J=2.0Hz), 4.73 (d, 1H, J=3.3Hz), 4.37 (t, 1H, J=2.6Hz), 4.08 (s, 5H), 3.89 (s, 3H), 3.62 (s, 3H), 2.35-2.18 (m, 2H), 1.73-1.60 (m, 2H), 0.88 (t, 3H, J=7.4Hz)。
Embodiment 11:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-ferrocenyl-2-(4-nitrobenzophenone) acetylene (0.2648g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of CTAB (0.0292g, 0.08mmol) and toluene (2mL), react 5 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) dark red solid, N-methoxyl group-6-ferrocenyl-5-(4-nitrobenzophenone) ferrocene also [c] pyridine-2 (1H)-one, productivity 83%, m.p.154 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC30H24Fe2N2O4[M+H]+589.0513,Found:589.0497.
1HNMR(300MHz,CDCl3): δ 8.32 (s, 1H), 8.09 (s, 1H), 7.77 (s, 1H), 7.06 (s, 1H), 5.68 (d, 1H, J=2.4Hz), 5.36 (d, 1H, J=2.7Hz), 4.87 (d, 1H, J=2.1Hz), 4.56 (d, 1H, J=2.6Hz), 4.36 (t, 1H, J=2.6Hz), 4.16 (s, 5H), 4.06 (s, 5H), 3.98 (t, 1H, J=3.2Hz), 3.58 (s, 3H), 3.25 (s, 1H)。
Embodiment 12:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), 1-ferrocenyl-2-(4-methoxyphenyl) acetylene (0.2528g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), CTAB (0.0292g, 0.08mmol) with the mixture of toluene (2mL), react 10 hours in 65 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.4) yellowish red color solid, N-methoxyl group-6-ferrocenyl-5-(4-anisyl) ferrocene also [c] pyridine-2 (1H)-one, productivity 70%, m.p.165 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC31H27Fe2NO3[M]+573.0690,Found:573.0638.
1HNMR(300MHz,CDCl3): δ 7.49 (d, 1H, J=8.4Hz), 7.01 (d, 1H, J=8.4Hz), 6.76 (d, 2H, J=11.7Hz), 5.65 (d, 1H, J=2.7Hz), 5.32 (d, 1H, J=2.7Hz), 4.85 (s, 1H), 4.49 (d, 1H, J=2.6Hz), 4.31 (d, 1H, J=3.3Hz), 4.13 (s, 5H), 4.03 (s, 5H), 3.96 (t, 1H, J=2.9Hz), 3.85 (s, 1H), 3.57 (s, 3H), 3.41 (s, 1H)。
Embodiment 13:
By N-methoxyl group ferrocene formamide (0.1036g, 0.4mmol), diphenyl diacetylene (0.1620g, 0.8mmol), palladium (0.0100g, 0.044mmol), Schweinfurt green (0.0020g, 0.011mmol), sodium acetate (0.0410g, 0.5mmol), the mixture of TBAB (0.0260g, 0.08mmol) and toluene (2mL), react 20 hours in 70 DEG C。After reactant mixture cooling, being initially charged 5mL water, be then extracted with ethyl acetate, extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=1:1, v/v, Rf=0.5) bright red solid, N-methoxyl group-5-phenyl-6-phenylacetylene base ferrocene also [c] pyridine-2 (1H)-one, productivity 75%, m.p.168 DEG C (dec.) are obtained。
HR-MS(ESI)(m/z):Calcd.forC28H21FeNO2[M+H]+460.1000,Found:460.1043.
1HNMR(300MHz,CDCl3): δ 7.74 (t, 2H, J=3.9Hz), 7.57-7.44 (m, 3H), 7.32-7.27 (m, 5H), 5.34 (t, 1H, J=2.7Hz), 4.66 (d, 1H, J=3.0Hz), 4.44 (t, 1H, J=2.7Hz), 4.19 (s, 3H), 4.15 (s, 5H)。
Embodiment 14:
By N-methoxyl group-5,6-diphenyl ferrocene also [c] pyridine-2 (1H)-one (0.0870g, 0.2mmol), tetrahydrochysene lithium aluminum (0.0300g, 0.8mmol) and 1, the mixture of 4-dioxane (1.0mL), is stirred at reflux 1 hour。Reaction is first cooled to room temperature after terminating, and then cools down in ice-water bath and adds water in downhill reaction mixture, is extracted with ethyl acetate, and extract saturated common salt water washing, organic facies anhydrous magnesium sulfate dries, and filtrate decompression is evaporated off solvent afforded crude material。Crude product is through column chromatographic isolation and purification (silica gel: 200-300 order, eluant: ethyl acetate/petroleum ether=2:1, v/v, Rf=0.5) obtaining red solid, 5,6-diphenyl ferrocene are [c] pyridine-2 (1H)-one also, productivity 80%, m.p.200 DEG C (dec.)。
HR-MS(ESI)(m/z):Calcd.forC25H19FeNO[M+H]+406.0894,Found:406.0861.
1HNMR(300MHz,CDCl3): δ 8.02 (br, 1H), 7.34-7.17 (m, 10H), 5.23 (d, 1H, J=2.2Hz), 4.64 (d, 1H, J=2.1Hz), 4.39 (t, 1H, J=2.6Hz), 4.12 (s, 5H)。
Claims (10)
1. N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds, is characterized in that, shown in its chemical constitution such as formula (I):
Wherein, R, R ' represent phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, to cyano-phenyl, to Fonnylphenyl, ferrocenyl, phenylacetylene base, propyl group, butyl, R, R ' can be identical, it is also possible to different。
2. the synthetic method of N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one compounds as claimed in claim 1, is characterized in that, comprise the following steps:
With palladium be catalyst, Schweinfurt green be promoter, quaternary ammonium salt and alkali for additive when, in reaction dissolvent, N-methoxyl group ferrocene formamide and alkynes carry out cyclization, generate N-methoxyl group ferrocene also [c] pyridine-2 (1H)-one derivant；Wherein, the mole dosage of described Schweinfurt green is the 1～5% of N-methoxyl group ferrocene formamide。
3. method as claimed in claim 2; it is characterized in that: described alkynes includes diaryl acetylene and alkylaryl acetylene, wherein said aryl be phenyl, p-methylphenyl, p-methoxyphenyl, p-nitrophenyl, to cyano-phenyl, to the one in Fonnylphenyl, ferrocenyl, phenylacetylene base；Described alkyl is the one in propyl group, butyl。
4. method as claimed in claim 2, is characterized in that: the mole dosage of described alkynes is 1～3 times of N-methoxyl group ferrocene formamide。
5. method as claimed in claim 2, is characterized in that: the mole dosage of described palladium is the 5～20% of N-methoxyl group ferrocene formamide。
6. method as claimed in claim 2, is characterized in that: described quaternary ammonium salt is any one in tetrabutyl ammonium bromide (TBAB), tetrabutylammonium iodide (TBAI), cetyl trimethylammonium bromide (CTAB)。
7. method as claimed in claim 2, is characterized in that: the mole dosage of described quaternary ammonium salt is the 10～50% of N-methoxyl group ferrocene formamide。
8. method as claimed in claim 2, it is characterized in that: described reaction dissolvent is one or more combinations in acetonitrile, oxolane, methanol, butanone, toluene, preferably, the consumption of described solvent is 10～50 times of N-methoxyl group ferrocene formamide weight。
9. method as claimed in claim 2, is characterized in that: reaction temperature is 30～80 DEG C, and the response time is 1～24 hour。
10. N-methoxyl group ferrocene also [c] pyridine-2 (1H) the-one compounds as claimed in claim 1 application in the compound containing ferrocene pyridone structure as intermediate synthesis。
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| CN114591376A (en) * | 2022-02-10 | 2022-06-07 | 浙江大学杭州国际科创中心 | Synthesis method of o-alkoxy ferrocene carboxamide |
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| HONGBAN ZHONG ET AL.: "Pd-catalysed synthesis of isoquinolinones and analoguesviaC–H and N–H bonds double activation", 《CHEM. COMMUN.》 * |
| SHAO-BO WANG ET AL.: "Synthesis of Ferrocene-Based Pyridinones through Rh(III)-Catalyzed Direct C−H Functionalization Reaction", 《ORGANOMETALLICS》 * |
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| CN114409713A (en) * | 2021-12-30 | 2022-04-29 | 山东师范大学 | N-unsubstituted ferrocenopyridone derivative and synthesis method thereof |
| CN114591376A (en) * | 2022-02-10 | 2022-06-07 | 浙江大学杭州国际科创中心 | Synthesis method of o-alkoxy ferrocene carboxamide |
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