Reações de fluoração em 5-aril(heteroaril)-7-(trifluormetil)-2- metilpirazolo[1,5-a]pirimidinas: síntese e estudo fotofísico

• Ano de defesa: 2024
• Autor(a) principal: Araújo, Juliane Nascimento
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/26339/001300001b4qh
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Química; UFSM; Programa de Pós-Graduação em Química; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Pirazolo[1,5-a]pirimidina; Fluoração; DAST; Selectfluor; Propriedades fotofísicas; Pyrazolo[1,5-a]pyrimidines; Fluorination; Photophysical properties; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/33804

This dissertation describes the results obtained for fluorination reactions in 5- aryl(heteroaryl)-7-(trifluoromethyl)-2-methylpyrazolo[1,5-a]pyrimidines (3), using DAST and Selectfluor, to obtaining new 5-aryl(heteroaryl)-3- (fluoro/fluoromethyl/difluoromethyl)-7-(trifluoromethyl)-2-methylpyrazolo[1,5- a]pyrimidines (5,6,8). The heterocyclic precursors 5-aryl(heteroaryl)-7- (trifluoromethyl)-2-methylpyrazolo[1,5-a]pyrimidines (3), were initially obtained by intermolecular cyclization reactions [3+3] between the dinucleophilic block (NCN) 5- amino-3-methyl-1H-pyrazole (1) and the dielectrophilic block (CCC) 4-alkoxy-4- aryl(heteroaryl)-1,1,1-trifluoro-3-alken-2-ones (β-ATC) (2). Firstly, the heterocycles 3 were then used as starting materials for a classic Vilsmeier-Haack formylation reaction functionalizing their position C3. This reaction led to the formation of a series of 5- aryl(heteroaryl)-7-(trifluoromethyl)-3-formyl-2-methylpyrazolo[1,5-a]pyrimidines (4). Subsequently, starting from compounds 4, a new series of six 5-aryl(heteroaryl)-3- (difluoromethyl)-7-(trifluoromethyl)-2-methylpyrazolo[1,5-a]pyrimidines (5) was obtained, in yields of 40 - 69%, by means of a nucleophilic fluorination reaction using the fluorinating reagent DAST. In addition, from compounds 3, electrophilic aromatic fluorination reactions were carried out using the fluorinating reagent Selectfluor, thus obtaining a second novel series of six examples of 5-aryl(heteroaryl)-3-fluoro-7- (trifluoromethyl)-2-methylpyrazolo[1,5-a]pyrimidines (6) in yields of 39–57%. Finally, the formyl-substituted compounds 4 were also subjected to reduction reactions of the 3- formyl substituent using NaBH4 (reducing reagent), to obtain a novel series of 5- aryl(heteroaryl)-7-(trifluoromethyl)-3-(hydroxymethyl)-2-methylpyrazolo[1,5- a]pyrimidines (7). However, after testing various reaction conditions for the deoxofluorination of compounds 7 with DAST, it was not possible to isolate or identify 3-fluormethyl substituted products (8). All new compounds 4-6 obtained in this work were characterized by melting point and full structurally elucidated by 1H, 13C and 19F NMR techniques, high-resolution mass spectrometry (HRMS) and single crystal X-ray diffraction analysis. In addition, the photophysical properties in solution, like absorption, emission, fluorescence quantum yield and Stokes Shifts were evaluated for all the series of 4, 5 and 6.