Nevels Nash E, Subera Luke, Bunce Richard A
Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA.
Molecules. 2024 Sep 12;29(18):4322. doi: 10.3390/molecules29184322.
A synthesis of benzo[]oxazoles by an -deprotonation--SAr cyclization sequence from anilide precursors is reported. Anilides derived from 2-fluorobenzaldehydes, activated toward SAr ring closure by C5 electron-withdrawing groups, were prepared and subjected to deprotonation-cyclization using 2 equiv. of KCO in anhydrous DMF. Following deprotonation at nitrogen, the delocalized anion cyclized from the amide oxygen to give high yields of benzo[]oxazoles. The temperature required for the cyclization of benzanilides correlated with the potency of the C5 activating group on the SAr acceptor ring with nitro (most potent) reacting at 90 °C (1 h), cyano reacting at 115 °C (1 h), methoxycarbonyl reacting at 120 °C (2 h), and trifluoromethyl (least potent) reacting at 130 °C (3 h). Acetanilides were more difficult to cyclize but generally required 4-6 h at these same temperatures for completion. Product purification was accomplished by recrystallization or chromatography.
报道了通过从酰苯胺前体经α-去质子化-SAr环化序列合成苯并[ ]恶唑。制备了由2-氟苯甲醛衍生的、被C5吸电子基团活化以进行SAr环化的酰苯胺，并在无水DMF中使用2当量的KCO进行去质子化-环化。在氮原子处去质子化后，离域阴离子从酰胺氧原子处环化，得到高产率的苯并[ ]恶唑。苯甲酰苯胺环化所需的温度与SAr受体环上C5活化基团的活性相关，硝基（活性最强）在90℃（1小时）反应，氰基在115℃（1小时）反应，甲氧基羰基在120℃（2小时）反应，三氟甲基（活性最弱）在130℃（3小时）反应。乙酰苯胺更难环化，但通常在这些相同温度下需要4-6小时才能完成。产物纯化通过重结晶或色谱法完成。
