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via Three Component Ring Transformation Le Thi Song and Nagatoshi - - PowerPoint PPT Presentation
via Three Component Ring Transformation Le Thi Song and Nagatoshi - - PowerPoint PPT Presentation
An Introduction to the Synthesis of Nitroanilines and Nitropyridines via Three Component Ring Transformation Le Thi Song and Nagatoshi Nishiwaki* School of Environmental Science and Engineering, Kochi University of Technology Tosayamada, Kami,
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Abstract: A file syntheis of nitropyridines and nitroanilines are achieved by using a three component ring transformation of dinitropyridone 1 with ketones in the presence
- f less nucleophilic ammonium acetate (NH4OAc) as nitrogen source.
When pyridone 1 was reacted with aromatic ketone in the presence of ammonium acetate, 6-arylated 3-nitropyriines 2 were formed besides diazabicyclo compounds 3. This method was also applicable to cycloalkanones and α,β- unsaturated ketones to afford cycloalka[b]pyridines 4 and 6- alkynylated/alkenylated pyridines 5, respectively. It was found to be possible to use aldehydes as the substrate, which leading to 3,5-disubstituted pyridines 6. On the other hand, when aliphatic ketones were employed as the substrate, two kinds of ring transformation proceeded. Namely, 2,6-disubstituted 4-nitroanilines 8 were formed in addition to nitropyridines 7. It was successful to apply this protocol to synthesis of N,N,2,6-tetrasubstituted nitroanilines 9 upon treatment of dinitropyridone 1 with ketone and amine in the presence of acetic acid. Keywords: Ring Transformation; Dinitropyridone; Nitropyridine; Nitroaniline; Multi Component Reaction
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Introduction
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Functionalized Heterocyclic Compounds are Useful for Medicines, Agricultural Chemicals, Dyes, Organic Electroluminescence etc. However, It is not Easy to Functionalize the Heterocyclic Framework. Hence, Efficient Functionalization Method should be Developed. Ring Transformation is One of the Solution for This Problem !!
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What is the Ring Transformation?
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Scrap & Built
Degenerate Type Diels-Alder Type
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NewType Ring Transformation (Nucleophilic Type)
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Electron-Deficiency and Good Leaving Group
Substrate Should Have
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Preparation of 1
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Reaction with 1,3-Dicarbonyl Compounds
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Problem
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Solution
1,3-Dicarbonyl Compounds are Useful Dinucleophilic Reagents, However, the Commercially Available Versatility is Low. If Simple Ketones can be Used, Synthetic Utility of This Method will be Considerably Improved.
Three Component Ring Transformation
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Results and Discussion
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Effect of Amount of NH4OAc
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A Plausible Mechanism
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Reaction with Other Aromatic Ketones
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Reaction with Hetero Aromatic Ketones
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Synthesis of TriSubstituted Pyridines
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Pd Catalyzed C-C Bond Formation
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Reaction with Unsaturated Ketones
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Reaction with Aldehydes
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Reaction Mechanism Using Aromatic Ketones
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Reaction Mechanism Using Aliphatic Ketones
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Synthesis of CycloAlka[b]Pyridines
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Friedel-Crafts Alkylation
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Limitations
- PolyAlkylation may Occur
- Rearrangement Proceeds to Afford Branched Alkyl Group
- Arylation cannot be Achieved
- Electron-Withdrawing Group Prevents
- Amino Group also Prevents
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Synthesis of NitroAnilines
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Synthesis of NitroAnilines
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Synthesis of N-Modified NitroAnilines
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Synthesis of N,N,2,6-Modified NitroAnilines
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Conclusions
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NH4OAc NH4OAc NH4OAc N O Me NO2 1 O2N Ar O N Ar NO2 N N H NO2 O Me Ar O2N + O R2 R1 O2N N R2 R1 H O R O2N N R O n O2N N n O R2 R1 NH2 O2N R2 N O2N R1 R1 R2 + NH4OAc R3R4NH NH4OAc N O2N R2 R1 R3 R4
AcOH
Metal-Free Simple Manipulation Easy Modification
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Acknowledgments
Professors
- Prof. Kazuhiko Saigo (Kochi Univ. Tech.)
- Prof. Kazuya Kobiro (Kochi Univ. Tech.)
- Dr. Haruyasu Asahara (Kochi Univ. Tech.)
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Members of Nishiwaki Lab.
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