Carbon Dioxide → 4(3H)-Quinazolinone, 3-(2-methylphenyl)-2-(2-oxopropyl)-

Participants

Reaction Steps

To a magnetically stirred solution of 5 mmol of LDA, prepared by mixing 2.1 ml (5 mmol) of n-butyllithium (2.4 M) and 0.71 g (7 mmol) of diisopropylamine in 25 ml of dy THF at 0° under nitrogen, was added 1.25 g (5 mmol) of methaqualone. After 30 minutes, the entire solution of lithio salt was transferred via syringe (50 ml) to an addition funnel which was attached to a three-necked 100 ml flask. The bottom half of the additional funnel was loosely enclosed in aluminum foil which formed a cup that held several small pieces of dry ice. To a solution of 4.40 g (50 mmol) of ethyl acetate in 60 ml of dry THF at 0°, was added dropwise the 5 mmol solution of lithio salt over a 65 minute period. After addition was complete, the clear yellow solution was poured into 100 ml of water containing 10 ml of 1 N NCl. The resulting solution was extracted twice with 200 ml portions of ether, which were combined, dried and concentrated. TLC analysis (ether-acetone, 98:2) revealed two spots, with methaqualone as the major component. Column chromatography afforded, on elution with hexane-ether (9:1), 0.14 g (8%) of 2-acetonyl-3-o-tolyl-4(3H)-quinazolinone (III n) as white crystals, mp 164°-165.6°. The 1H NMR spectrum was identical with samples prepared by the general sodium hydride acylation procedure described subsequently.

Provenance & Evidence