Síntese sequencial linear de 6-((1,2,3-triazol-4-il)metil)-4,5- dimetil-2,6-di-hidro-1h-pirrolo[3,4-d]piridazinonas via reações de N-alquilação, CuAAC e ciclocondensação

• Ano de defesa: 2017
• Autor(a) principal: Magalhães, Hernane Tolentino
• Orientador(a): Bonacorso, Helio Gauze
• Banca de defesa: Frizzo, Clarissa Piccinin , Fantinel, Leonardo
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Centro de Ciências Naturais e Exatas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química
• Departamento: Química
• País: Brasil
• Palavras-chave em Português: Pirróis; Triazóis; Pirrolo[3,4-d]piridazinonas; N-alquilação; CuAAC; Reação de ciclocondensação [4+2] com hidrazinas; HCl
• Palavras-chave em Inglês: Pyrroles; Triazoles; Pyrrolo[3,4-d]pyridazinones; N-alkylation; CuAAC; [4+2] cyclocondesation reaction with hydrazine
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/15179

This dissertation presents a synthetic route for obtaining a series of eight 6-((1H-1,2,3- triazol-4-yl)methyl)-1H-pyrrolo[3,4-d]pyridazin-1-ones with yields of 40-70%. The synthetic route comprises three distinct steps: (i) N-alkylation reaction of polysubstituted pyrrole with propargyl bromide, (ii) Cu(I) catalyzed 1,3-dipolar cycloaddition reaction (CuAAC - copper(I)- catalyzedalkyne-azidecycloaddition) of system 1-(prop-2-yn-1-yl)-1H-pyrrole with some organic azides and (iii) [4+2] cyclocondensation reaction of carbonyl substituents of the pyrrole ring with hydrazine hydrochloride. Initially, we synthesized two examples of azido vinylesters aryl substituted by Knoevenagel condensation reaction between various aldehydes and methyl azidoacetate in 74- 92 % yields. Subsequently, we performed the [3+2] cycloaddition reaction between the azide vinylesters and acetylacetone, obtaining two examples od polysubstituted pyrroles using methyl 4-acetyl-5-methyl-2-phenyl-1H-pyrrole-3-carboxylate and methyl 4-acetyl-2-(4- methoxyphenyl)-5-methyl-1H-pyrrole-3-carboxylate as starting material. The two polysubstituted pyrroles were subjected to N-alkylation reaction with propargyl bromide, which were obtained in yields of 88 and 89%. Subsequently, eight examples of 1- (1H-1,2,3-triazol-4-yl)-1H-pyrroles in 48-88% yields were synthesized by CuAAC reaction between the two precursors and four organic azides, generated in situ by sodium azide and four different organic halides, namely, chloromethyl-benzene, 1-chloro-4-(chloromethyl)-benzene, 1- (chloromethyl)-4-methoxybenzene and 1-bromooctane. Thus, the eight target molecules (6- ((1H-1,2,3-triazol-4-yl)methyl)-1H-pyrrolo[3,4-d]pyridazin-1-ones) were obtained from a [4+2] cyclocondensation reaction between hydrazine hydrochloride and the methylcarboxylate and acetyl substituents present in positions 3 and 4 of the pyrrole rings. The structure of the compounds was characterized by combined techniques of NMR Spectroscopy (1H and 13C {1H}), Gas Chromatography coupled to Mass Spectrometry (GCMS), High Resolution Mass Spectrometry (HRMS) and X-ray Diffraction.