Application
4,6-Dichloroquinazoline is widely used due to its high pharmacological activity and diverse biological activities. It possesses two carbon-nitrogen double bonds and is widely found in various alkaloids and organic molecules with biopharmacological activity. Its activities include antitumor, antimalarial, anti-inflammatory, antibacterial, anticonvulsant, antituberculosis, and antihypertensive effects.
Synthesis
General procedure for the synthesis of 4,6-dichloroquinazoline from 6-chloroquinazolin-4-one: 6-chloroquinazolin-4-one (400 mg, 2.21 mmol, 1.0 eq.), phosphoryl chloride (1.99 mL, 21.4 mmol, 9.64 eq.) and triethylamine (0.99 mL, 7.11 mmol, 3.21 eq.) were mixed under nitrogen protection in a reaction flask. The reaction mixture was stirred and refluxed for 2.5 hours at room temperature. Upon completion of the reaction, the solvent was removed by rotary evaporation and the residue was recrystallized twice with toluene to give a brown solid. The solid was dissolved in dichloromethane (25 mL) and the organic phase was washed twice with saturated ammonium chloride solution (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to give a brown solid. The crude product was purified by silica gel column chromatography with an eluent of 9:1 to 3:1 hexane/ethyl acetate to give 4,6-dichloroquinazoline (300 mg) as an off-white solid in 68% yield. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 9.16 (s, 1H), 8.33 (s, 1H), 8.17 (apparent t, 2H, J = 7 Hz).
References
[1] Patent: WO2015/164374, 2015, A1. Location in patent: Paragraph 00349; 00351
[2] Oriental Journal of Chemistry, 2010, vol. 26, # 4, p. 1401 - 1406
[3] Patent: US2005/54626, 2005, A1. Location in patent: Page/Page column 38
[4] Patent: WO2016/91774, 2016, A1. Location in patent: Page/Page column 21
[5] Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie, 1982, vol. 37, # 7, p. 907 - 911
