一种喹唑啉酮(苯并咪唑及苯并噻唑)类化合物的通用合成方法

chem有机方法2023-07-227.5K+

今天分享的内容是一种喹唑啉酮,苯并咪唑及苯并噻唑类结构的构建方法，作者以亚磷酸为催化剂，β-酮酯类化合物与邻氨基苯甲酰胺(邻氨基苯胺及邻氨基苯硫酚)发生环合反应生成相应的产物。该方法的反应条件温和，底物普适性较广，可达到中等及以上收率，对以上三类结构的构建具有十分重要的意义。

该文献报道的方法及操作

操作:A 5 mL Schlenk tube equipped with a magnetic stir bar was charged with o-aminophenyl derivative (1, 5, or 6 0.2 mmol), β-diketone/ketoester (2 or 4 0.26 mmol), H₃PO₃(0.02 mmol, 10 mol %), and ethanol (0.5 mL).The reaction mixture was stirred at 50 °C for 15 h. The reaction was monitored by GC or GC-MS. After completion of the reaction, the resulting solution was cooled to room temperature, and neutralized with saturated solution of NaHCO₃.The product was extracted with EtOAc, dried over anhydrous Na₂SO₄,and concentrated in vacuo. The crude product was purified by flash column chromatography(eluent:ethyl acetate/petroleum ether = 1/2-1/5) on silica gel to afford the desired product.

底物普适性考察

^aReaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-ketoester2 (0.26 mmol), 50% H₃PO₃ (10 mol %, 0.02 mmol), EtOH (0.5mL) in 5 mL Schlenk tube, 50 °C, 15 h. ^bIsolated yield. ^c80°C, 24 h. ^d100 °C, 24 h.

^aReaction conditions: 2-aminobenzamide 1 (0.2 mmol), β-diketone4 (0.26 mmol), 50% H₃PO₃ (10 mol %, 0.02 mmol), EtOH (0.5mL) in 5 mL Schlenk tube, 50 °C, 15 h. ^bIsolated yield. ^c80°C, 24h. ^d100 °C, 24 h. ^e130 °C, 24 h.

一种喹唑啉酮(苯并咪唑及苯并噻唑)类化合物的通用合成方法第4张

^aReaction conditions: o-substituted aniline 5 or 6 (0.2 mmol), β-ketoester 2 (0.26 mmol), 50% H₃PO₃ (10 mol %, 0.02 mmol),EtOH (0.5 mL) in 5 mL Schlenk tube, 50 °C, 15 h. ^bIsolated yield.^c80 °C, 24 h.

反应机理的探究及推测

作者通过采用捕捉反应中间态的方法，对反应的机理进行研究。如下图:

一种喹唑啉酮(苯并咪唑及苯并噻唑)类化合物的通用合成方法第5张