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Synlett 2005(20): 3079-3082  
DOI: 10.1055/s-2005-922747
LETTER
© Georg Thieme Verlag Stuttgart · New York

Design and Synthesis of Novel Trichloromethylated N-Azolylmethyl-1H-­pyrimidin-2-ones and Related N-Methylenaminones

Nilo Zanatta*, Darlene C. Flores, Simone S. Amaral, Helio G. Bonacorso, Marcos A. P. Martins, Alex F. C. Flores
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
Fax: +55(55)32208756; e-Mail: zanatta@base.ufsm.br;
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Publikationsverlauf

Received 23 September 2005
Publikationsdatum:
28. November 2005 (online)

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Abstract

Reaction of 4-trichloromethyl-1H-pyrimidin-2-ones with 5-bromo-1,1,1-trichloro(fluoro)-4-methoxy-alk-3-en-2-ones affords 1-[5,5,5-trichloro(fluoro)-2-methoxy-4-oxopent-2-en-1-yl]-4-trichloromethyl-1H-pyrimidin-2-ones. Reaction of the latter trichloromethylated compound with amines, hydroxylamine, and hydrazines affords a series of 1-(2-alkylamine-5,5,5-trichloro-4-­oxopent-2-en-1-yl)-4-trichloromethyl-1H-pyrimidin-2-ones and 1-(5-trichloromethyl-5-hydroxy-4,5-dihydro-3-azol-3-ylmethyl)-4-trichloromethyl-1H-pyrimidin-2-ones, respectively.

Key words

N-pyrazolylmethylpyrimidinones - pyrimidines - pyrazoles - enamino ketones - halogenated heterocycles

23

Pyrimidine 5 - General Procedure.
A mixture of 3 (3.0 g, 10.12 mmol), pyrimidinone 1 (2.16 g, 10.12 mmol) and K2CO3 (1.4 g, 10.12 mmol) was refluxed in anhyd acetone (30 mL) or anhyd MeCN for compound 2, for 16 h under vigorous stirring. The reaction was carried out in two phases. The crude product, a white solid, precipitated and was collected under vacuum filtration. The white solid was washed with cold distilled H2O (2 × 15 mL), acetone (2 × 10 mL), dried, and recrystallized from CHCl3-MeOH (3:1). White powder, yield 60%; mp 208 °C (decomp.).
IR (KBr): νmax = 1669, 1617, cm-1. 1H NMR (400 MHz, DMSO-d 6): δ (pyrimidinone) = 7.06 (d, 1 H, 3 J H5-H6 = 7.0 Hz, H-5), 8.50 (d, 1 H, 3 J H6-H5 = 7.0 Hz, H-6); δ (enone) = 3.82 (s, 3 H, OMe), 5.35 (s, 2 H, CH2), 6.22 (s, 1 H, H-3). 13C NMR (100 MHz, DMSO-d 6): δ (pyrimidinone) = 95.2 (CCl3), 98.3 (C-5), 153.8 (C-2), 153.4 (C-6), 170.8 (C-4); δ (enone) = 51.9 (CH2), 56.0 (OMe), 90.1 (C-3), 96.7 (CCl3), 174.9 (C-2), 179.8 (C-4). Anal. Calcd for C11H8Cl6N2O3 (428.91): C, 30.80; H, 1.88; N, 6.53. Found: C, 30.69; H, 1.94; N, 6.55.

24

N -Isoxazolylmethylpyrimidinone 9.
A mixture of 5 (0.5 g, 1.17 mmol), hydroxylamine hydrochloride (0.15 g, 2.12 mmol), pyridine (0.1 mL, 2.12 mmol), and anhyd MeOH (15 mL) was stirred under reflux for 24 h. The solvent was removed under reduced pressure and a yellow oil was obtained. To this oil was added cold H2O (10 mL) and the mixture was stirred for 20 min in order to precipitate the compound 9. The white powder precipitated and was filtrated and dried under vacuum. The product was purified by recrystallization from CHCl3-MeOH (3:1). Yield 80%; mp 229 °C (decomp.). IR (KBr): νmax = 3196, 1638 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ (pyrimidinone) = 7.09 (d, 1 H, 3 J H5-H6 = 7.0 Hz, H-5), 8.50 (d, 1 H, 3 J H6-H5 = 7.0 Hz, H-6); δ (isoxazole) = 3.30 (d, 1 H, 2 J 4Hb-4Ha = 19.0 Hz, 4-Hb), 3.70 (d, 1 H, 2 J 4Ha-4Hb = 19.0 Hz, 4-Ha), 4.95 (s, 2 H, CH2), 8.60 (s, 1 H, OH). 13C NMR (100 MHz, DMSO-d 6): δ (pyrimidinone) = 95.3 (CCl3), 99.0 (C-5), 153.3 (C-6), 153.7 (C-2), 170.8 (C-4); δ (isoxazole) = 44.7 (C-4), 46.9 (CH2), 101.4 (CCl3), 111.5 (C-5), 155.7 (C-3). Anal. Calcd for C10H7Cl6N2O3 (429.90): C, 27.94; H, 1.64; N, 9.77. Found: C, 27.87; H, 1.72; N, 9.71.

26

Selected Spectroscopic Data and Elemental Analysis of 11d.
Yield 70%; mp 139 °C (decomp.). IR (KBr): νmax = 3472, 3405, 1668, 1618 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ (pyrimidinone) = 7.03 (d, 1 H, 3 J H5-H6 = 7.0 Hz, H-5), 8.47 (d, 1 H, 3 J H6-H5 = 7.0 Hz, H-6); δ (pyrazole) = 3.47 (d, 1 H, 2 J 4Hb-4Ha = 20.0 Hz, 4-Hb), 3.78 (d, 1 H, 2 J 4Ha-4Hb = 20.0 Hz, 4-Ha), 5.02 (d, 1 H, 2 J = 16.0 Hz, CH2), 5.13 (d, 1 H, 2 J H-H = 16.0 Hz, CH2), 8.05 (s, 1 H, OH), 8.15 (s, 1 H, CONH2). 13C NMR (100 MHz, DMSO-d 6): δ (pyrimidin-one) = 95.4 (CCl3), 99.1 (C-5), 153.4 (C-2), 152.6 (C-6), 170.7 (C-4); δ (pyrazole) = 47.5 (C-4), 48.5 (CH2), 104.4 (CCl3), 100.6 (C-5), 153.9 (C-3), 157.3 (CONH2). Anal. Calcd for C11H9Cl6N5O3 (471.94): C, 27.99; H, 1.92; N, 14.84. Found: C, 27.66; H, 1.83; N, 14.95.