A novel approach to the synthesis of 6-substituted uracils in three-step, one-pot reactions.
From the commercial 6-chloro-2,4-dimethoxypyrimidine (1) and by a photostimulated reaction with Me(3)Sn(-) ions, 2,4-dimethoxy-6-(trimethylstannyl)pyrimidine (2) was obtained in 95% yield. By the cross-coupling reaction of 2 with 1-iodonaphthalene as electrophile catalyzed by Pd (Stille reaction), 2,4-dimethoxy-6-(naphthalen-1-yl)pyrimidine (9) was obtained in 76% yield. By hydrolysis of 9, 6-(1-naphthyl)uracil was obtained in 98% of isolated yield. When the three steps (S(RN)1 reaction-cross coupling reaction-hydrolysis) were performed in a one-pot reaction, 6-substituted uracils (1-naphthyl, 4-chlorophenyl, 3-chlorophenyl, 2,3,4,5,6-pentafluorophenyl) were obtained (43-57%) of isolated pure products. When the electrophile was a benzoyl chloride, 6-benzoyl uracil (54%) and 6-(2-chlorobenzoyl) uracil (49%) were obtained in isolated pure products.
Bardagí
Javier I
JI
INFIQC, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.
Rossi
Roberto A
RA
D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D014498:Uracil / Q000138:chemical synthesis*
D014498:Uracil