Uses
2,3''-Dichloroacetophenone is used as a reagent in the synthesis of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β). Also used as a reagent in the synthesis of benzimidazolyl pyridinones as insulin-like growth factor I (IGF-1R) kinase inhibitors.
Synthesis
Method A: A hexane solution of butyl lithium (300 mL, 0.474 mol) was slowly added dropwise to 1,2-dichlorobenzene (104.58 g, 0.711 mol) dissolved in dry tetrahydrofuran (2 L) under nitrogen protection, keeping the reaction temperature at -70°C. After the dropwise addition, the reaction solution was continued to be stirred for 1 hour at -70°C. The reaction solution was then transferred to acetic anhydride (290.35 g, 2.84 mol) dissolved in anhydrous tetrahydrofuran (1 L) via double-headed needle. Subsequently, the reaction solution was transferred to acetic anhydride (290.35 g, 2.84 mol) dissolved in anhydrous tetrahydrofuran (1 L) via a double-ended needle at the same temperature. After addition, the reaction mixture was stirred at -70 °C for 1 h, followed by natural warming to room temperature. The reaction mixture was poured into ice (5 L), stirred thoroughly and allowed to stand at room temperature overnight. The aqueous phase was extracted with ether (3 x 1.5 L), and the organic phase was combined and washed sequentially with water (3 x 750 mL), saturated sodium bicarbonate solution (3 x 750 mL) and brine (1 x 750 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated to obtain a yellow liquid crude product. The crude product was placed in a hot water bath and the residual 1,2-dichlorobenzene and acetic anhydride were removed under high vacuum to finally obtain 2,3-dichloroacetophenone (67.2 g, 75% yield). The product was analyzed by infrared spectroscopy (IR), nuclear magnetic resonance (NMR) and thin-layer chromatography (TLC, silica gel plate, the unfolding agent was chloroform), the product was of high purity and contained only a small amount of impurities, so it was not further purified.
References
[1] Patent: US5912345, 1999, A
[2] Patent: US5925755, 1999, A
