Summary of synthesis of a quinazolinone-type heterocycle from acetoanthanilic acid and aniline (hydrochloride salt).
- Goal: prepare the hydrochloride salt of the target heterocycle under strictly anhydrous conditions to maximize yield.
- Key reagents/conditions: dry toluene, dry acetoanthanilic acid, dry aniline in slight excess, phosphorus trichloride as a dehydrating agent; cold-water condenser; moisture exclusion; stirring is crucial.
- Process outline: form a suspension in dry toluene, slowly add PCl3 to generate water-free environment, observe white fumes and temperature rise, proceed to precipitation; reflux for about 1.5 hours; distill off to remove water azeotropically and isolate crude product.
- Workup: basify with NaOH to convert to freebase, filter, then convert back to hydrochloride salt via dissolution in hot acetone and addition of HCl; isolate crude product.
- Purification: dissolve in hot acetone, re-crystallize to obtain white microcrystalline powder; final yield 56% based on starting benacetylanthanilic acid.
- Notes: moisture exclusion and vigorous stirring are crucial; HCl gas evolution requires good ventilation; final product can be recrystallized for purity.
