Diethylamine: A smart organocatalyst in eco-safe and diastereoselective synthesis of medicinally privileged 2-amino-4H-chromenes at ambient temperature

Abstract

Diethylamine has been demonstrated to be an efficient organocatalyst in the diastereoselective synthesis of Bcl-2 protein antagonist (HA-14-1) and of its structural analogues by one-pot condensation between salicylaldehyde and three different C-H acids, viz. ethyl cyanoacetate, phenylsulfonyl acetonitrile, and malononitrile. Easy commercial availability of the catalyst at extremely low cost and avoidance of conventional work-up as well as purification procedures qualifies this scalable protocol for a ''near-ideal synthesis''.

A simple, economical, and environmentally benign protocol for the synthesis of 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines at ambient temperature

“…However, with the choice of diethylamine as the catalyst, we obtained the desired pyridine derivative at room temperature. In this context, based on our earlier experiences on aza, phospha as well as carba-Michael addition reaction studies (41)(42)(43), we propose that the initial exothermy that results upon addition of the catalyst to the reaction mixture might be one of the driving forces of the reaction. To give credence to this philosophy, three model reactions were performed using anisaldehyde, malononitrile, and thiophenol (1:2:1 equiv.)…”

“…However, to the best of our knowledge, its use as a catalyst in multicomponent reactions remained ignored. In fact, we have recently demonstrated the use of diethylamine in multicomponent synthesis of 2-amino-3-cyano-4H-chromenes employing Knoevenagel-phospha-Michael as well as Knoevenagel-carba-Michael cascade pathway (42,43). Since the synthesis of pyridine-3,5-dicarbonitriles, 7, involves Knoevenagel-carba as well as thia-Michael cascade pathway, it was quite logical for us to examine the use of diethylamine in this multicomponent reaction.…”

“…Interestingly, most of the reported protocols with variation in the catalyst used require elevated temperature and to the best of our knowledge, there are only three protocols that are operable at ambient temperature (24,31,37). Keeping in view the growing medicinal importance of pyridine-3,5-dicarbonitriles and our continued interest in the development of eco-benign synthetic methodologies (38)(39)(40)(41)(42)(43)(44), we surmised that introduction of an energyefficient, eco-safe, and easily adaptable protocol for their synthesis at ambient temperature is highly desirable (Scheme 1a).…”

A domino reaction for the synthesis of 2-amino-4 H -chromene derivatives using bovine serum albumin as a catalyst

“…The 2-amino-3-cyano-4H-chromene MX58151 (2) with a *Manuscript Click here to view linked References M a n u s c r i p t 2 3-bromo-4,5-dimethoxyphenyl substituent at the 4-position was considered as a potential agent with multiple action modes against the breast cancer cell line T47D, the lung cancer cell line H1299 and the colorectal cancer cell line DLD-1, and it might have an advantage for the treatment of the drug-resistant cancers as it retains activity in tumor cells resistant towards current antimitotic agents, taxanes (including Taxol and Taxotere), and Vinca alkaloids [3]. Some methods of synthesis of 2-amino-4H-chromenes have already been reported, such as the chemical one pot synthesis of 2-amino-4H-chromenes [5][6][7][8][9], methods resulting in good yields [10][11][12][13] and quite short reaction times [14][15][16][17]. Generally, 2-amino-4H-chromenes are synthesized by multi-component reactions involving in Knoevenagel condensation of salicylic aldehydes with active methylene followed by a intramolecular cyclization step, and have employed organic bases, ionic liquids or organic small molecules as catalysts [10,18,19].…”

“…Some methods of synthesis of 2-amino-4H-chromenes have already been reported, such as the chemical one pot synthesis of 2-amino-4H-chromenes [5][6][7][8][9], methods resulting in good yields [10][11][12][13] and quite short reaction times [14][15][16][17]. Generally, 2-amino-4H-chromenes are synthesized by multi-component reactions involving in Knoevenagel condensation of salicylic aldehydes with active methylene followed by a intramolecular cyclization step, and have employed organic bases, ionic liquids or organic small molecules as catalysts [10,18,19]. Moreover, harsh conditions were required in some reported synthetic methods such as reflux, microwave or electrolysis [1][2][3].…”