Estudo de reações de N-alquilação de pirimidin-2-onas: síntese de novos análogos nucleosídicos modificados

• Ano de defesa: 2008
• Autor(a) principal: Brondani, Patrícia Bulegon
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/26339/00130000036dq
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; BR; Química; UFSM; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Química; Química orgânica; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/10402

This work presents a study of the N-alkylation reactions of 4- (trichloromethyl)pyrimidin-2(1H)-one(2), 5-bromo-4-methoxy-4-(trichloromethyl)-3,4-dihydropyrimidin-2-(1H)-one (7), 4-methoxy-4-(trichloromethyl)-3,4-dihydropyrimidin-2(1H)-one (6), cytosine (1), 3-benzoylpyrimidine-2,4(1H,3H)-dione (or 3-benzoyl-uracil) (10), 3-benzoyl-5-methylpyrimidine-2,4(1H,3H)-dione (or 3-benzoyl-thymine) (11). The pyrimidines were tested with the alkylating agents chloro-acetamide (3a) and diethyl 2-bromomalonate (3b) in the presence of polar solvents (acetone, DMF, THF) and base (K2CO3 e NaH). The pyrimidines 4, 6, 8, and 9 were satisfactorily alkylated and in good to excellent yields. However, we were unable to alkylate 4-methoxy-4-(trichloromethyl)-3,4- dihydropyrimidin-2(1H)-one (6) and the cytosine (1). 3-Benzoyl-thymine 11 was only alkylated successfully in the presence of the alkylating agent 1. The alkylated products, 4-trichloromethyl-1-(methylcarbamoyl)-1H-pyrimidin-2-one (10), 4-trichloromethyl-1-(1,3-diethoxymalon-2-yl)-1H-pyrimidin-2-one (11), 5- bromo-4-trichloromethyl-1-(methylcarbamoyl)-4-methoxy-3,4-dihydropyrimidin- 2(1H)-one (14), 5-bromo-4-trichloromethyl-1-(1,3-diethoxymalon-2-yl)-4- methoxy-3,4-dihydropyrimidin-2(1H)-one (15), 3-benzoyl-1-(methylcarbamoyl)- 1H-pyrimidin-2,4-dione (18), 3-benzoyl-1-(1,3-diethoxymalon-2-yl)-1H-pyrimidin-2,4-dione (19) e 3-benzoyl-5-methyl-1-(methylcarbamoyl)-1H-pyrimidin-2,4-dione (20), can be considered acyclic nucleoside analogues. In the second stage of this work, a study of the substitution reactions on 1-[(E)-5,5,5-trichloro-2-methoxy-4-oxo-penten-2-yl]4-trichloromethyl-1Hpyrimidin-2-one (22) in the presence of amines and aminoalcohols (synthesis of enamino ketones), was done: 1-(5,5,5-trichloro-2-ethylamine-4-oxopent-2-enyl)- 4-trichloromethyl-1H-pyrimidin-2-one (24b), 1-(5,5,5-trichloro-2-propylamine-4-oxopent-2-enyl)-4-trichloromethyl-1H-pyrimidin-2-one (24c), 1-(5,5,5-trichloro-2-isopropylamine-4-oxopent-2-enyl)-4-trichloromethyl-1H-pyrimidin-2-one (24d),1-(5,5,5-tricloro-2-phenethylamino-4-oxopent-2-enyl)-4-tricloromethyl-1Hpyrimidin-2-one (24h), 1-(5,5,5-trichloro-2-(2-hydroxyethylamine)-4-oxopent-2-enyl)-4-trichloromethyl-1H-pyrimidin-2-one (24n), 1-(5,5,5-trichloro-2-(2-hydroxypropylamine)-4-oxopent-2-enyl)-4-trichloromethyl-1H-pyrimidin-2-one(24o). When the amine was methylamine the disubstitution product , 4-trichloromethyl-1-[N-methyl-3-(methylamino)but-2-enamide-4-yl]pyrimidin-2(1H)-one (24a), was obtained and, when the nucleophile was 2,2-dimethylethanolamina the product, 1-[(4,4-dimethyloxazolidin-2-ylidene)methyl]-4-(tricloromethyl)pyrimidin-2(1H)-one (24p), was obtained. Most products precipitated in the reaction vessel as pure compounds and in good yields.