Unorthodox synthesis, biological activity and DFT studies of novel and multifunctionalized naphthoxocine derivatives

Abstract

A new promising protocol has been developed for the synthesis of scarce oxocine derivatives through addition of amine-based nucleophiles to chromonylidene benzothiazol-2-ylacetonitrile under metal free reaction conditions in moderate to good yields.

Synthesis and Reactivity of Electron-Deficient 3-Vinylchromones

“…Chromone 47, obtained from 3-formylbenzochromone and 2-cyanomethyl-1,3-benzothiazole, reacts with piperidine in refluxing dioxane in the same way as chromones 11, with the only exception that the expected product 48 at the final stage of the reaction undergoes a Dimroth rearrangement to form heterocycle 49 (Scheme 23). 44 Heating chromones 11a,b in refluxing 95% ethanol containing 1 drop of piperidine results in partial hydrolysis of the cyano group to the amide group, leading to 2-pyridones 50 as recyclization products of the -pyrone ring (Scheme 24). 45 On the other hand, treatment of chromone 11a at X = CO 2 Et with a 2% aqueous solution of NaOH at 70 °C gives pyrano[4,3-b]chromene 51, which is formed as a result of the attack by the hydroxide anion of the C-2 atom, opening of the pyrone ring and addition of hydroxyl groups at the activated double bond and the cyano group.…”

“…Similar products were obtained with the same active methylene compounds based on 3-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromen-6-yl)acrylonitrile. 62 A report 44 has described a number of reactions of chromone 47 with various dinucleophiles (Scheme 40), but the structure of the obtained compounds cannot be considered definitively proven due to the lack of 2D experiments and X-ray diffraction data.…”

“…Scheme 22 Reactions of 3-(chromon-3-yl)acrylonitriles with primary aminesChromone 47 obtained from 3-formylbenzochromone and 2cyanomethyl-1,3-benzothiazole reacts with piperidine in refluxing dioxane in the same way as chromones 11, with the only exception that the expected product 48 at the final stage of the reaction undergoes a Dimroth rearrangement to form heterocycle 49 (Scheme 23) 44. …”

Naphthyl bearing 1,3,4-thiadiazoleacetamides targeting the parasitic folate pathway as anti-infectious agents: in silico, synthesis, and biological approach

“…Here, we connected naphthyl-bearing 1,3,4-thiadiazole pharmacophore with substituted secondary amine conjugates through a flexible acetamide linker. In medicinal chemistry, naphthalene establishes a versatile and multifaceted platform and appears as a promising moiety in drug design due to its various biological [19][20][21][22][23] and clinical 24,25 applications. The naphthyl ring formed π-π interaction with the amino acid residue of the active site [26][27][28][29] ((I) and (II)) (Fig.…”