Lewis‐Acid‐Catalysed Activation of Nitriles: A Microwave‐Assisted Solvent‐Free Synthesis of 2,4‐Disubstituted Quinazolines and 1,3‐Diazaspiro[5.5]undec‐1‐enes

Abstract

Two different modes of cyclization take place to synthesize quinazoline, quinazolinone, and 1,3‐diazaspiro[5.5]undec‐1‐ene derivatives through the Lewis‐acid‐catalysed activation of both aliphatic and aromatic nitriles in a single‐step, solvent‐free, and transition‐metal‐free reaction. An amidine is expected to form as an intermediate; this then undergoes intramolecular cyclization in a one‐pot reaction sequence. The reaction is carried out under microwave irradiation using trimethylsilyltrifluoromethane sulfonate (TMSOTf) as a catalyst and nitriles as a nitrogen source with the respective reaction partners.

Microwave-Assisted Synthesis of Quinazolines and Quinazolinones: An Overview

“…A solvent-free, transition-metal-free, rapid, and efficient reaction to prepare 2,4-disubstituted quinazolines 49 via the Lewis-acid-catalyzed activation of nitriles and intramolecular cyclization in a one-pot reaction sequence was developed (Saikia et al, 2018 ). The reaction was performed in the presence of a catalytic amount of trimethylsilyltrifluoromethane sulfonate (TMSOTf) under MWI.…”

“…Although the aforementioned reactions are considered as the most important transition-metal catalyses, a plethora of vital reactions can be effectively catalyzed by various transition metals including reductive elimination, oxidative addition, and transmetallation. Transition metal catalysis has also found extensive applications in the convenient and efficient synthesis of a wide variety of heterocyclic systems (Ma et al, 2017 ; Ramanathan and Liu, 2017 ; Tiwari and Bhanage, 2017 ; Chatterjee et al, 2018 ; Saikia et al, 2018 ; Chen et al, 2020 ; Debabrata et al, 2020 ; Ghosh et al, 2020 ; Janardhanan et al, 2020 ; Jiang et al, 2020 ; Kanwal et al, 2020 ; Kojima and Matsunaga, 2020 ; Li and Zhang, 2020 ; Nagata and Obora, 2020 ; Neto and Zeni, 2020a , b ; Pal et al, 2020 ; Ratmanova et al, 2020 ; Sahiba and Agarwal, 2020 ; Sonawane et al, 2020 ; Xuan et al, 2020 ). However, the literature survey revealed only an example of zinc (Shi et al, 2004 ), a limited number of iron-catalyzed (Melvin et al, 1992 ; Valderrama et al, 1999 ; Kanth et al, 2006 ; Yin et al, 2012 ; Gopalaiah et al, 2017 , 2019 ; Raut and Bhanage, 2017 ; Eidi et al, 2018 ), and relatively more copper-catalyzed reactions, leading to the synthesis of quinazoline and quinazolinone derivatives (Melvin et al, 1992 ; Chatterjee et al, 2018 ; Potuganti et al, 2018 ; Liang et al, 2019 ; Rodrigues et al, 2019 ; Donthiboina et al, 2020 ).…”

Intramolecular cyclization ofN-cyano sulfoximines by N–CN bond activation

“…29 Because of the presence of a lone pair of electrons on the nitrogen atom, the cyano group acts as a Brønsted and Lewis base. [30][31][32][33][34]…”

Iron‐Based Imidazolium Salt as Dual Lewis Acid and Redox Catalyst for the Aerobic Synthesis of Quinazolines

“…Another interesting strategy involves the use of anthranilic acid derivatives and surrogates thereof, such as anthranilamides, [17] anthranilonitriles, [18] o ‐halobenzonitriles, [19] or isatoic anhydrides, [20] which reacted with different electrophiles leading to the target quinazoline unit. Moreover, o ‐acylanilines have been also employed in combination with benzaldehydes, [21] acyl halides, [22] amides, [23] nitriles, [24] methylarenes, [25] or amines, [17a] to assemble the quinazoline moiety. The latter methodology is reasonably well documented, although most protocols have shortcomings in terms of catalyst selection, the use of external oxidants or hazardous solvents.…”