Novel Synthesis of 3-(N-Substituted Amino)-1-Isoindolenones From 2-Cyanobenzaldehyde With Amines

Abstract

Various 3-(N-substituted amino)-1-isoindolenones were readily synthesized quantitatively by reactions of 2-cyanobenzaldehyde with amines at low temperature such as 20 °C.

Tandem driven dynamic combinatorial resolution via Henry–iminolactone rearrangement

“…{ Following these surprising results, the literature was probed for similar transformations. Observations where cyanoalcohols were transformed to lactams were found, [18][19][20] however in all cases requiring a partly different mechanistic route in order to form the final product. These routes also resulted in products that, despite their heterocyclic complexity, are of limited synthetic utility.…”

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

“…Unexpectedly, in the case of 2‐cyanobenzaldehyde 7 , the cyclized isoindolinone derivative 8 was isolated instead of the desired Schiff's base, Scheme A. A plausible mechanism is suggested where the initial step is the nucleophilic addition of the amine 2 to the formyl group of 7 affording the adduct 7a , which subsequently cyclizes to 7b by intramolecular nucleophilic addition of the hydroxyl group to the cyano group of 7a , followed by conversion to the isoindolinone derivative 8 , Scheme B …”

Quick and easy access to N-Mannich bases of 1-isoindolinones by catalytic electroactivation of primary and secondary amines and tandem reaction with 2-formylbenzonitriles

“…In this work we wish to present our results concerning the tandem reaction of 2-formylbenzonitriles with electroactivated primary and secondary amines to afford N-Mannich bases 1, a class of compounds with easily conceivable versatility for a wide gamut of applications ranging from pharmacology, use as intermediates in drug synthesis, as well as ligands for catalytic purposes. 6 Despite their potential, a literature survey reveals that, after the pioneering study by R. Sato 7 which shows the uncatalyzed access to compounds 1 when a large excess (more than 2000-fold molar excess) of amine is used, no more convenient catalyzed procedures have been reported starting from 2-formylbenzonitriles. However, other routes have been proposed (for example, the reaction of aldimines with isocyanates using a rhenium catalyst), 8 demonstrating the interest for these kinds of heterocyclic scaffolds.…”

“…See DOI: 10.1039/c4nj01606h is initiated is not clear in detail, such a good turnover of the electron transfer process is highly desirable also in terms of atom-economy since, in parallel, it can drastically reduce the amount of the supporting electrolyte required to carry out the electrolysis. 12 Taking into account these experiments, we hypothesized a reaction pathway which involves the electrochemically initiated deprotonation of the hemiaminal intermediate A, and the subsequent cascade of reactions (cyclization-rearrangement) 7,13 as depicted in Fig. 1.…”