Estudo teórico da reação intramolecular de Schmidt em 3-azidoalquilcicloalcanonas: do mecanismo aos efeitos de substituintes na seletividade
Schmidt’s intramolecular reactions became important to produce fused and bicyclic lactams from azidoalkylcycloalkanes, being also designated as Schmidt-Aubé reactions. By this means, Tani and Stoltz synthesized the lactam 1-azabicyclo [2.2.2] octan-2-one ([2.2.2]), known as 2-quinoclidone, which cha...
| Autor principal: | Kosteczka, Guilherme Lemos |
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| Formato: | Dissertação |
| Idioma: | Português |
| Publicado em: |
Universidade Tecnológica Federal do Paraná
2021
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| Assuntos: | |
| Acesso em linha: |
http://repositorio.utfpr.edu.br/jspui/handle/1/23655 |
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| Resumo: |
Schmidt’s intramolecular reactions became important to produce fused and bicyclic lactams from azidoalkylcycloalkanes, being also designated as Schmidt-Aubé reactions. By this means, Tani and Stoltz synthesized the lactam 1-azabicyclo [2.2.2] octan-2-one ([2.2.2]), known as 2-quinoclidone, which challenged scientists for several decades. This synthesis, which occurred with 76% of the product [2.2.2] and 24% of the isomeric lactam, inspired the proposal of this work. Theoretical calculations were performed to (i) elucidate the mechanism, investigate the influence of the (ii) ring size and (iii) –SCH3, phenyl, –CF3, –CH3 and t-butyl groups installed in each carbon alpha of 3-azidoalkylcycloalcanones in selectivity. Results confirmed a two-step mechanism, consistent with the nucleophilic attack of the azide nitrogen atom to protonated carbonyl group, forming an azidohydrin, followed by the rate determinant step migration of one of the alpha carbon simultaneous to N2 departure. Calculations at M06-2X/6-311++G(d,p) level of theory presented best agreement to the experimental yield (error of 1,8%). Results showed the migration of the –SCH3 substituted alpha carbon is favored by the substituent as it assists the leaving group departure by cation...lone pair interactions. Similar but minor effect was observed with phenyl group, which features weaker cation...pi interactions with leaving group. Electron withdrawing group –CF3 presented no influence on N2 departure, but rather inhibited alpha carbon migration where it is installed due to intense hyperconjugation between –CF3 and the C–C bond, which favors the competitive reaction. Steric hindrance caused by methyl or t-butyl substituents on the leaving group favor the formation of the lactam in the alkylated carbon. All substituents evaluated were able to invert the selectivity compared to the main system (except –CH3) if installed on the appropriate alpha carbon. Results obtained in this work help to understand the factors involved in the bicyclic lactams selectivity and may encourage the synthesis of new compounds. |
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