A Simple Metal-Free Cyclization for the Synthesis of 4-Methylene-3-Substituted Quinazolinone and Quinazolinthione Derivatives: Experiment and Theory

Abstract

A new series of 3-substituted 4-methylene-quinazolinthiones and 4-methylene-quinazolinones were synthesized in moderate to excellent yield through a simple reaction of 2-aminoacetophenones with isocyanates or isothiocyanates. The reaction shows good tolerance of many important functional groups in the presence of air and water under metal-free conditions. Only water is produced as a coproduct, rendering this “green” methodology a highly versatile and eco-friendly alternative to the existing methods for the construction of the quinazolinone/quinazolinthione framework. We have interpreted the reaction mechanism by use of quantum chemical calculations on the basis of state-of-the-art computational methods SMD-B3LYP-D3(BJ)/BS1//B3LYP/BS1.

A Synthetic Protocol for the Construction of Chroman‐Spiroquinazolin(thi)one Framework via a Metal‐Free, Three‐Component, Domino, Double Annulations

“…A is protonated in the presence of a Bronsted acid and then followed by an annulation to yield an intermediate C . One molecule of water is then removed to afford a 4‐methylene‐quinazolinone intermediate D. D can be isolated and the NMR data were identical to those reported previously [14] . On the other hand, the starting material 3 undergoes an elimination under thermal condition to give an o ‐quinone methide intermediate E .…”

Expeditious Approach to Indoloquinazolinones via Double Annulations of o-Aminoacetophenones and Isocyanates

“…However, when the reaction was performed directly from 1 and 2, low yields (<20%) of the desired products were given. We then prepared the intermediates 4 using aqueous NaOH as the catalyst as reported previously, 17 and 4 was carried out under standard conditions. Moderate yields of the desired 6-and 7-membered rings were afforded (Scheme 2, eqs 1 and 2).…”

“…We have previously reported a cyclization of 2-aminoacetophenones with isocyanate to form 4-methylenequinazolinones (4) promoted by sodium hydroxide. 17 Encouraged by several reports of palladium-catalyzed C−H activation and C−C bond formation, 18 we envisioned that the in situ resultant compound 4 could perform a palladiumcatalyzed intramolecular C−C bond formation to afford indolo [1,2-c]quinazolinone in a one-pot fashion. Herein, we wish to report an efficient and atom-economical method for direct cascade reaction of o-aminoacetophenones and aryl isocyanates for a one-pot formation of indolo [1,2-c]quinazolinones via intermediate 4 (Scheme 1d).…”

“…Thus, a great demand exists for a straightforward, convenient protocol for the synthesis of indolo­[1,2- c ]­quinazolinones. We have previously reported a cyclization of 2-aminoacetophenones with isocyanate to form 4-methylene-quinazolinones ( 4 ) promoted by sodium hydroxide . Encouraged by several reports of palladium-catalyzed C–H activation and C–C bond formation, we envisioned that the in situ resultant compound 4 could perform a palladium-catalyzed intramolecular C–C bond formation to afford indolo­[1,2- c ]­quinazolinone in a one-pot fashion.…”

Sequential Oxidative Fragmentation and Skeletal Rearrangement of Peroxides for the Synthesis of Quinazolinone Derivatives

“…16f Recently, to overcome the use of expensive catalysts or ligands, Ma and co-workers reported a variant protocol for the synthesis of 4-alkenylquinazolinons and 4-alkenylquinazolinthione by using catalytic amounts of NaOH under reflux. 17 Although there are pros and cons of the reported method for the quinazolinone derivatives, designing an attractive and newer approach for these heterocycles is an evergrowing paradigm in chemical synthesis. From the literature, it is evident that no peroxide rearrangement has been used for the construction of the quinazolinone derivatives.…”