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. / Este trabalho apresenta um estudo das reações de N-alquilação de 4-triclorometil-1H-pirimidin-2-ona (4), citosina (5), 5-bromo-4-metóxi-4-triclorometil-1,3H-pirimidin-2-ona (6), 4-metóxi-4-triclorometil-1,3H-pirimidin-2-ona (7), 3-benzoil-1H-pirimidina-2,4-diona (ou 3-benzoil-uracila) (8), 3-benzoil-5-metil-1H-pirimidina-2,4-diona (ou 3-benzoil-timina) (9). As pirimidinonas foram testadas com os agentes alquilantes cloro-acetamida (1) e malonato de dietila
bromado (2) na presença de solventes polares (acetona, DMF, THF) e meio básico (K2CO3 ou NaH). As pirimidinonas 4, 6, 8 e 9 foram alquiladas satisfatoriamente e em rendimentos que variaram de bons a ótimos. Não foi possível realizar a alquilação da 4-metóxi-4-triclorometil-1,3H-pirimidin-2-ona
(7) e da citosina (5). A pirimidinona 3-benzoil-timina (9) somente foi alquilada com sucesso na presença do alquilante 1. Os produtos alquilados, 4-triclorometil-1-(metil carbamoil)-1H-pirimidin-2-ona (10), 4-Triclorometil-1-(1,3-dietoximalon-2-il)-1H-pirimidin-2-ona (11), 5-bromo-1-(metil carbamoil)-4-
metóxi-4-triclorometil-1,3H-pirimidin-2-ona (14), 5-bromo-4-triclorometil1-(1,3-dietoximalon-2-il)-4-metóxi--1,3H-pirimidin-2-ona (15), 3-benzoil-1-(metilcarbamoil)-1H-pirimidin-2,4-diona (18), 3-benzoil-1-(1,3-dietoximalon-2-il)-1Hpirimidin-
2,4-diona (19) e 3-Benzoil-5-metil-1-(metil carbamoil)-1H-pirimidina-2,4-diona (20), podem ser considerados análodos nucleosídicos acíclicos. Na segunda etapa do trabalho realizou-se um estudo das reações de substituição em 1-[(E)-5,5,5-tricloro-2-metóxi-4-oxo-penten-2-il-]-4-triclorometil-1H-pirimidin-2-ona (22) na presença de aminas primárias e aminoálcoois levando a uma série de enamino cetonas triclorometiladas: 1-(5,5,5-tricloro-2-etilamino-4-oxopent-2-enil)-4-triclorometil-1H-pirimidin-2-ona (24b), 1-(5,5,5-
tricloro-2-propilamino-4-oxopent-2-enil)-4-triclorometil-1H-pirimidin-2-ona (24c), 1-(5,5,5-tricloro-2-isopropilamino-4-oxopent-2-enil)-4-triclorometil- 1H-pirimidin-2-ona (24d), 1-(5,5,5-tricloro-2-fenetilamino-4-oxopent-2-enil)-4-triclorometil-1H-pirimidin-2-ona (24h), 1-(5,5,5-tricloro-2-(2-hidroxietilamino)-4-oxopent-2-enil)-4-triclorometil-1H-pirimidin-2-ona (24n), 1-(5,5,5-tricloro-2-(2-hidroxipropilamino)-4-oxopent-2-enil)-4-triclorometil-1H-pirimidin-2-ona (24o).
Quando a amina utilizada foi metilamina o produto de disssubstituição, 4-triclorometil-1-[-N-metil-3-(metilamino)but-2-enamida-4-il]-1H-pirimidin-2-ona (24a), foi obtido e, quando foi utilizado 2,2-dimetiletanolamina o produto de
ciclização, 1-[(2-ilideno-4,4-dimetiloxazolidin)metil]-4-triclorometil-1H-pirimidin-2-ona (24p), foi obtido. De maneira geral, a maioria dos produtos precipitaram de forma pura no meio reacional quando utilizou-se excesso de nucleófilo,
sendo obtidos em rendimentos moderados.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsm.br:1/10402 |
| Date | 15 January 2008 |
| Creators | Brondani, Patrícia Bulegon |
| Contributors | Zanatta, Nilo, Martins, Marcos Antonio Pinto, Flores, Alex Fabiani Claro |
| Publisher | Universidade Federal de Santa Maria, Programa de Pós-Graduação em Química, UFSM, BR, Química |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFSM, instname:Universidade Federal de Santa Maria, instacron:UFSM |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 100600000000, 400, 500, 300, 500, 500, 233dc1de-ab03-4f57-9b85-e40dc01a2d4f, 3dcc3902-10f2-4bc6-8a22-f60aa6526887, a8bc3c8e-4034-458b-a211-6be4a0d7001b, 17a00027-8984-4561-9228-46697f540c2b |
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