Paper
Isocyanide Cyclization Reactions: 4‐Methylene‐4H‐benzo[d][1,3]oxazine, 3‐Benzyl‐4‐methylene‐3,4‐dihydroquinazolines and 3‐(4‐Benzyl)‐3H‐quinazolin‐4‐ones – Experiment and Theory
Published Aug 1, 2013 · Benedikt Neue, Ralph Reiermann, R. Fröhlich
European Journal of Organic Chemistry
9
Citations
0
Influential Citations
Abstract
2-Isocyanoacetophenone (3a) was found to be an easily accessible starting material for the unexpected formation of various heterocyclic systems. Thus, a hitherto unknown rather unstable 4-methylene-4H-benzoxazine derivative 4, which could be characterized by NMR spectroscopy, was formed in situ by the reaction of 3a in the presence of weak acids. In the presence of benzylamines, a new class of 3,4-dihydroquinazoline derivatives 6 and their oxidation products, quinazolin-4-ones 9, were obtained. The starting materials and products were completely characterized by spectroscopic and X-ray analysis. The scope and limitations of these cyclization reactions were investigated under various reaction conditions. High-level quantum chemical calculations were carried out to elucidate the mechanisms leading to scaffolds 4 and 6. The calculations suggest that the formation of 4 and 6 involves the generation of an unusual six-membered N-heterocyclic carbene or its C-protonated form as a reaction intermediate, followed by tautomerisation. This mechanism might also be applicable to other isocyanide cyclization reactions.
Isocyanoacetophenone can easily form new heterocyclic systems, such as 4-methylene-4H-benzoxazine and 3,4-dihydroquinazoline derivatives, through the generation of an unusual six-membered N-heterocyclic carbene intermediate and
Full text analysis coming soon...