Structure of the Condensed Product of Aromatico-Aminonitrile with Carbonyl Compound and Its Mechanism

Abstract

Friedländer reaction is one of the most important routes to synthesize the quinoline and its derivatives, which possesses excellent bioactivity and photo-electricity activity. Recently, a new skeleton product besides the normal Friedländer quinoline was discovered by the condensation of aromatic o-aminonitrile and carbonyl compounds, and this phenomenon has attracted many researchers, but the skeleton structure of new conversion is debated. Herein, this paper reviews on the development progress of this new kind reaction. According to recent research results, the skeleton structure of new conversion was assigned as quinazolinone, which was confirmed by the 13 C NMR, FT-IR, and single-crystal X-ray diffraction deterimations. Therefore, this new conversion is abbreviated as PDF conversion, which means a new conversion from Pinner to Dimroth rearrangement in the Friedländer reaction. The total reaction mechanism of o-aminonitrile with carbonyl compound was proposed. Keywords aromatic o-aminonitrile; divergent conversion; Friedländer conversion; quinazolinone; benzoxazine; product structure 邻氨基芳香腈是一类非常有用的双官能团化合物, 相邻的氨基、氰基的推、拉电子效应赋予整个体系特有 的化学性质, 由此可以合成一系列含氮杂环化合物 [1～7]. 这类物质的典型转化是它与羰基底物经由 Friedländer 缩合制备 4-氨基吡啶及其相关衍生物 [8～10]. 有意思的是 当我们用 2-氨基-5-硝基苯甲腈(1a)与环己酮(2a)在氯化 锌催化下回流制备抗老年痴呆药物他克林的 7-硝基衍 生物时, 除了得到预期的目标物 3a 外, 还得到一种浅黄 色的固体 [11]. 当我们改变底物结构时, 依然可以得到除 预期目标物外的相似结构的浅黄色固体. 这类新产物的 骨架结构早期被认为是 2H-3,1-苯并噁嗪(4) (图 1), 但随 后我们将该物质的骨架结构调整为喹唑啉酮 5 [12～22]. 这是国内外首次发现这类 Friedländer 反应在生成 正常喹啉衍生物的同时还能产生不同骨架的新产物, 这