Publicação
Reactivity studies on chromene derivatives
| Resumo: | Chromenes are privileged scaffolds as they comprise multiple natural and synthetic derivatives having pharmacological activity, both in vitro and in vivo. Substituted 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts were recently prepared from the reaction of an appropriate salicylaldehyde and 1-(cyanomethyl)pyridinium chloride, in two steps. This work presents a study of the reactivity of these salts, to be used as precursors of novel chromene derivatives. In a previous work, 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts were found to react with nitrogen nucleophiles as described in the Zincke reaction, yielding 3-aminochromenes. In this study, the reaction with active methylene compounds (malononitrile and ethyl cyanoacetate) allowed the isolation of 7-((2- oxo-2H-chromen-3-yl)amino)hepta-2,4,6-trienenitriles. These compounds are the postulated intermediates of the Zincke reaction and are herein described for the first time. They incorporate a side chain bearing a push-pull conjugated system that can be used for further functionalization. In the reaction of 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts with ethyl cyanoacetate, trace amounts of 3-amino-2-cyano-3-(2-oxo-2H-chromen-3- yl)acrylates were isolated. Following a retrosynthetic approach, these compounds were prepared in good to quantitative yields, by a one pot reaction, from the corresponding salicylaldehyde and ethyl cyanoacetate. Despite the simplicity of the synthesis, this is the first time that 3-amino-2-cyano-3-(2-oxo-2H-chromen-3-yl)- acrylates were isolated. The reaction of 1-(2-oxo-2H-chromen-3yl)pyridinium chloride salts with methyl ketones allowed the isolation of the bridged compounds 1-(4-oxo-2-phenyl-3,4,5,6- tetrahydro-2H-2,6-methanobenzo[g][1,3]oxazocin-5-yl)pyridinium chloride salts in poor yield. The reaction showed to be sensitive to minor variations in the experimental procedure. The competitive formation of 2,4-diarylpyridinone after elimination of pyridinium chloride was considered responsible for the low yield of the bridged compounds. |
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| Autores principais: | Gomes, João Guilherme Louçano Domingues |
| Assunto: | Ciências Naturais::Ciências Químicas |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Chromenes are privileged scaffolds as they comprise multiple natural and synthetic derivatives having pharmacological activity, both in vitro and in vivo. Substituted 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts were recently prepared from the reaction of an appropriate salicylaldehyde and 1-(cyanomethyl)pyridinium chloride, in two steps. This work presents a study of the reactivity of these salts, to be used as precursors of novel chromene derivatives. In a previous work, 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts were found to react with nitrogen nucleophiles as described in the Zincke reaction, yielding 3-aminochromenes. In this study, the reaction with active methylene compounds (malononitrile and ethyl cyanoacetate) allowed the isolation of 7-((2- oxo-2H-chromen-3-yl)amino)hepta-2,4,6-trienenitriles. These compounds are the postulated intermediates of the Zincke reaction and are herein described for the first time. They incorporate a side chain bearing a push-pull conjugated system that can be used for further functionalization. In the reaction of 1-(2-oxo-2H-chromen-3-yl)pyridinium chloride salts with ethyl cyanoacetate, trace amounts of 3-amino-2-cyano-3-(2-oxo-2H-chromen-3- yl)acrylates were isolated. Following a retrosynthetic approach, these compounds were prepared in good to quantitative yields, by a one pot reaction, from the corresponding salicylaldehyde and ethyl cyanoacetate. Despite the simplicity of the synthesis, this is the first time that 3-amino-2-cyano-3-(2-oxo-2H-chromen-3-yl)- acrylates were isolated. The reaction of 1-(2-oxo-2H-chromen-3yl)pyridinium chloride salts with methyl ketones allowed the isolation of the bridged compounds 1-(4-oxo-2-phenyl-3,4,5,6- tetrahydro-2H-2,6-methanobenzo[g][1,3]oxazocin-5-yl)pyridinium chloride salts in poor yield. The reaction showed to be sensitive to minor variations in the experimental procedure. The competitive formation of 2,4-diarylpyridinone after elimination of pyridinium chloride was considered responsible for the low yield of the bridged compounds. |
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