A green protocol for synthesis of benzo-fused N,S-, N,O- and N,N-heterocycles in water

Abstract

A fast and efficient protocol which is associated with readily available starting materials, mild conditions, excellent yields, and a broad range of the products in synthetic chemistry, was established for synthesis of quinoxaline, benzoxazine, and benzothiazine derivatives in water under catalyst-free conditions.

Hydroamination Reactions of Alkynes with ortho‐Substituted Anilines in Ball Mills: Synthesis of Benzannulated N‐Heterocycles by a Cascade Reaction

“…Furthermore, the resulting lactam structure has a higher stability than that of the alternative thioester. These findings are in accordance with many literature protocols discussing the synthesis of benzothiazines in solution34, 41c, d, 48 or in a solvent‐free manner 14. 42 In some cases, the formation of products with a similar structure to 4 was postulated 30d.…”

“…Similarly to the formation of benzoxazines from o ‐aminophenols ( 1 g , 8 – 12 ; Table 3), products 20 a and 20 b prefer to adopt a Z configuration due to the presence of hydrogen bonding between the NH group and the ester carbonyl group. In comparison with other methods available for the synthesis of 20 (in accordance with Scheme ),30a–c, 31, 34, 41 the present method and also other solvent‐free methods are fast and reduce the reaction time to less than 10 min 14. 42 A solvent‐free reaction in the presence of Yb(OTf) 3 resulted in similar yields but double the reaction time was required 43.…”

“…The FTIR spectra of recrystallized products were almost superposable to those of the crude reaction mixture. However, a subsequent reaction during sample preparation by dissolution cannot be excluded, although the literature reports mainly water or alcohols as the preferred solvents 34. The fact that simple mixing of the reagents on a Petri dish results in almost quantitative yields after only a few minutes14 indicates that a fast and direct analysis is required for the product mixtures, ideally without pretreatment (like extraction).…”

“…However,asubsequent reaction during sample preparation by dissolution cannot be excluded, although the literature reports mainly water or alcohols as the preferred solvents. [34] Thef act that simple mixing of the reagents on aP etri dish results in almost quantitative yields after only af ew minutes [14] indicates that af ast andd irecta nalysis is required for the product mixtures,i deally withoutp retreatment (like extraction). The use of ATRF TIR spectroscopy is one option because no sample workup is necessary andt he time gap between sampling and measurement can be reduced to less than 40 s. The FTIR spectra of the products from the reactiono f1g and 2a or 2b contain several signals, which are suitable for semiquantitative analysiso ft he reaction progress.…”

Antimicrobial Evaluation of New Quinoxaline Derivatives Synthesized by Selective Coupling with Alkyl Halides and Amino Acids Esters

“…Moreover, they displayed potent antimycobacterial activity , anti‐infectives , and topoisomerase inhibition activity . Quinoxaline derivatives were also reported as NMDA receptor antagonists and DNA cleaving agents .…”