These common heterocyclic compound, 60702-69-4, name is 2-Chloro-4-fluorobenzonitrile, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Recommanded Product: 2-Chloro-4-fluorobenzonitrile
Cool a solution of diisopropylamine (80.6 niL, 0.575 mol) in THF (1 L) to about -5 0C using an ice water/MeOH bath. Add /z-butyllithium (2.5 M in hexanes, 212 mL, 0.530 mol) dropwise over 1 h via a syringe pump (4 mL/min) while maintaining the reaction temperature between -5 to 0 0C during the addition. Stir the lithium diisopropylamide (LDA) solution for 1 h at 0 C and then transfer it via canula, over 1 h, to a -78 0C solution of 2-chloro-4-fluoro-benzonitrile (68.7 g, 0.442 mol) in THF (1 L). Allow the temperature of the reaction mixture to warm to about -65 0C during the initial addition of the LDA solution; however, keep the internal temperature below -70 0C during the remainder of the LDA addition. Keep the temperature of the resulting dark red-orange reaction mixture below -70 0C for 5 h and add iodomethane (251.2 g, 1.77 mol, ~3 mL/min) at such a rate that the reaction temperature is maintained below -65 0C during the addition. Allow the reaction mixture to slowly warm overnight. After stirring for 14 h, the temperature of the reaction mixture is -5 0C. Quench the reaction with saturated aqueous ammonium chloride (500 mL) and water (750 mL) and dilute with diethyl ether (about 2 L). Separate the layers and extract the aqueous layer with diethyl ether (about 1 L). Dry the combined organic layer (about 5.5 L) over MgSO4, filter, and concentrate to afford the crude title compound as a red-brown oily solid (about 86.7 g). Subject the crude residue (dry loaded on silica gel using methylene chloride) to flash chromatography (silica gel (10 x 30 cm), gradient of 99: 1 to 93:7 hexane/EtOAc) to obtain the title compound (56.7 g, 76%) as a white solid, m.p. 63 – 65 0C; 1H NMR (300 MHz, CDCl3): delta 7.54 (dd, J= 8.6, 5.6 Hz, IH), 7.08 (dd, J = 8.6, 8.6 Hz , IH), 2.36 (d, / = 2.4 Hz, 3H).
The synthetic route of 2-Chloro-4-fluorobenzonitrile has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ELI LILLY AND COMPANY; WO2006/124447; (2006); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts