Ethyl 4-chloroacetoacetate → 7-chloromethyl-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one

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Reaction Conditions

Reaction Steps

2-amino-5-phenyl-1,3,4-thiadiazole (10 g) was reacted with ethyl 4-chloro-acetoacetate (18.6 g) in polyphosphoric acid (100 g) under stirring at 100° C. for 1 hour. After cooling, dilution with ice water and neutralization with 35% NaOH, the precipitate was filtered and washed with water until neutral: crystallization from methanol gave 7-chloromethyl-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one, m.p. 201°-202° C. (11.6 g), which was reacted with triphenylphosphine (12.4 g) in acetonitrile (500 ml) under stirring at reflux temperature for 48 hours. After cooling the precipitate was filtered and washed with isopropyl ether to give (5-oxo-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-7-yl)-methyl-triphenylphosphonium chloride, m.p. 295°-300° C. (20 g), which was suspended in dimethylsulphoxide (100 ml) and treated dropwise with potassium terbutoxide (5 g) dissolved in dimethylsulphoxide (100 ml) at a temperature of about 20° C. The solution of the ylide so obtained was then reacted with benzaldehyde (4.55 g) at room temperature for 90 minutes. After dilution with ice water the precipitate was filtered and washed with water: crystallization from methanol gave 5.1 g of 2-phenyl-7-trans-(2-phenyl-ethenyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one, m.p. 217°-219° C., N.M.R. (CDCl3) δp.p.m.: 6.34 (s) (1H, C-6-proton), 6.82 (d) (1H, β-ethenyl proton), 7.58 (d) (1H,α-ethenyl proton), 7.12-7.98 (m) (10H, phenyl protons); JHαHβ =16 Hz.

Provenance & Evidence