Malononitrile dimer as a privileged reactant in design and skeletal diverse synthesis of heterocyclic motifs

Abstract

Malononitrile dimer as a precursor reactant has been extensively applied in the diversity-oriented synthesis of various heterocyclic motifs, bis-heterocyclic compounds, fused heterocycle derivatives, bicyclic bridged heterocyclic scaffolds, and highly substituted carbocyclic compounds. These remarkable products were synthesized via various types of reactions, such as cycloaddition, cyclocondensation, cascade/domino/tandem reactions along with multi-component reactions. In addition, the flexibility and high reactivity of malononitrile dimer as a multi-functional reagent and its potential to the preparation of novel beneficial scaffolds as well as biologically active molecules signify it as a suitable building block in total synthesis, medicinal chemistry, and dyes. In the present review, the advances in the chemistry of malononitrile dimer as a potent reagent in organic synthesis have been reported in the past to now.

Reactions of Malononitrile Dimer with Isothiocyanates

“…2-Аminо-1,1,3-tricyanopropene 1, which is readily prepared by the dimerization of malononitrile [1], is a polyfunctional reagent widely used in synthetic organic chemistry. Heterocyclizations involving malononitrile dimer 1 are known since the middle of XX century and are fairly well studied (for reviews, see [2][3][4]). Nevertheless, there are contradictory data in the literature concerning the regioselectivity of the reactions of malononitrile dimer 1 with isothiocyanates.…”

Metal-free domino amination-Knoevenagel condensation approach to access new coumarins as potent nanomolar inhibitors of VEGFR-2 and EGFR

“…Hereupon, we used the above-mentioned reaction conditions albeit with one-pot, two-step domino strategy. First, base (1.0 equiv, 3a/3b)-catalyzed dimerization of malononitrile (2.0 equiv, 2b) into non-isolated 2-amino-1,1,3-tricyanopropene (7) [46] that has drawn tremendous attention of interest due to its comprehensive implementations in the synthesis of heterocyclic compounds that manifest diverse biological and pharmaceutical properties [47]. At the same time, in another conical flask, suspension solution of 4-(pyrrolidin-1-yl)-3-formylcoumarin (5a)/ 4-(piperidin-1-yl)-3-formylcoumarin (5b) in MeOH (2 mL) were prepared from direct amination of 1a (1.0 equiv) and 3a/3b (1.5 equiv).…”

Methylene Components Exchange in the Reaction of Cyanoacetohydrazide with 2-Amino-4-arylbuta-1,3-diene-1,1,3-tricarbonitriles

“…Malononitrile dimer (2-aminoprop-1-ene-1,1,3-tricarbonitrile, 10) is a reactive multifunctional reactant widely used in organic synthesis (see reviews [24,25]). Continuing studies in the field of heterocyclization reactions of malononitrile dimer [26][27][28][29][30][31][32], herein we studied the reaction of arylmethylidene derivatives of malononitrile dimer 11 with cyanoacetohydrazide 1.…”