Synthesis of Nicotinamide and Isonicotinamide Derivatives via Multicomponent Reaction of Alkyl Isocyanides and Acetylenic Compounds in the Presence of Nicotinic or Isonicotinic Acid

Abstract

An effective route to functionalized nicotinamide and isonicotinamide derivatives is described. This involves the reaction of nicotinic or isonicotinic acid with acetylenic compounds in the presence of alkyl isocyanides. The reactive 1:1 intermediates obtained from the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates or dibenzoylacetylene was trapped by OH-acids such as nicotinic or isonicotinic acid to produce dialkyl 2-(alkylamino)-5-[alkyl(3-or 4-pyridylcarbonyl)amino]-3,4-furandicarboxylate, N 3 -(alkyl)-N 3 -[3,4-dibenzoyl-5-(alkylamino)-2-furyl]nicotinamide, and N 4 -(alkyl)-N 4 -[3,4-dibenzoyl-5-(alkylamino)-2-furyl]isonicotinamide derivatives.

Synthesis of 4-Hydroxy-1H-pyrrole-2,3-dicarboxylic Acid Derivatives: Unusual Coupling of Acetylenic Esters and α-Amino Acids in the Presence of Cyclohexyl Isocyanide or N,N′-Dicyclohexylcarbodiimide

“…Among other interesting syntheses, we could prepare nicotinamide and isonicotinamides. 10 In a related study in the multicomponent area, we incorporated a-amino acids under similar conditions. To this end, as a preliminary step in IMCRs/DAAD and a-amino acids reactions, we synthesized dialkyl 4-hydroxy-5-alkyl(or aryl)-1H-pyrrole-2,3-dicarboxylates in good yields.…”

Fe3O4‐supported Schiff‐base copper (II) complex: A valuable heterogeneous nanocatalyst for one‐pot synthesis of new pyrano[2,3‐b]pyridine‐3‐carboxamide derivatives

“…[31,32] Owing to these unique features, MNPs-immobilized catalysts have been found to be more promising candidates in comparison to their non-supported homogeneous counterparts. [46][47][48][49] Pyran and fused pyran derivatives constitute important core units in an extensive number of naturally occurring and biologically active compounds. [33][34][35][36][37] Moreover, during the last few decades, health and environmental issues have emerged as the key motivation for improvement and development of environmentally friendly industrial and chemical processes.…”

“…[42][43][44][45] Therefore, these reactions provide the scientists an efficient, time saving and atom economical approach to a wide variety of organic and bioorganic molecules including heterocyclic compounds. [46][47][48][49] Pyran and fused pyran derivatives constitute important core units in an extensive number of naturally occurring and biologically active compounds. [50] Moreover, 4Hpyrans have been widely used as useful intermediates for the synthesis of a variety of other heterocyclic compounds such as pyranopyridine derivatives.…”

An Unprecedented Synthesis of Eight-Membered-Ring Cyclic Thioimidic Esters by a Three-Component Reaction

“…As part of our current studies [18][19][20][21] on the development of new routes to heterocyclic system we wish to report a simple one-pot three-component reaction between dialkyl acetylenedicarboxylates or dibenzoylacetylene and isocyanides in the presence of elemental sulfur to yield cyclic thioimidic esters. The thioimidates are useful intermediates, 22 and recently a preparation was reported that uses imidoyltriphenylphosphonium methylides.…”