Recyclization of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates into Bicyclic N-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives by the action of nitrogen-containing 1,4- and 1,5-binucleophiles

Abstract

Reactions of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates with nitrogen-containing 1,4-and 1,5-binucleophiles (o-phenylenediamine, o-aminobenzenethiol, ethane-1,2-diamine, and propane-1,3-diamine) involved recyclization, leading to the formation of fused N-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamides, diethyl 6,6′-oxybis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates), and diethyl 6,6′-[ethane-1,2-diyl(or propane-1,3-diyl)diimino]bis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates), depending on the reactant ratio. The sequence of formation of intermediate recyclization products was determined.We recently developed a procedure for the synthesis of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates Ia and Ib [1]. Unlike methods reported previously [2-4], the developed procedure ensures high selectivity and utilizes accessible initial compounds. 2-Oxo-1,2-dihydropyridines I were used as substrates in cyclocondensations with nitrogen-containing 1,2-, 1,3-, and 1,5-binucleophiles [1, 2, 5]. The reactions of dihydropyridines Іa and Ib with propane-1,3-diamine involved recyclization [5].The goal of the present work was to estimate the scope of application of the above recyclization and examine how the ratio of initial 1,2-dihydropyridin-2-one Ia or Ib and difunctional nucleophile [o-phenylenediamine (IIa), o-aminobenzenethiol (IIb), ethane-1,2-diamine (Va), and propane-1,3-diamine (Vb)] affects the reaction direction. We were also interested in elucidating the reaction mechanism (i.e., the transformation sequence and structure of intermediate products) and unambiguously determining the structure of recyclization products. Recyclizations with participation of o-phenylenediamine (IIa) and o-aminobenzenethiol (IIb), leading to the formation of benzimidazole, quinoxaline, and 1,4-benzothiazine derivatives, were the subjects of recent publications [6][7][8], which demonstrated increased interest in such reactions.Compounds Ia and Ib were found to react with nucleophiles IIa, IIb, Va, and Vb along two pathways. When the reactant ratio was 1 : 1 or 1 : 2, the products were not substituted 2H-pyran-2-ones (as we presumed previuously [5]) but mixtures of fused N-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives ІІІa-IIId or VIa-VId and diethyl 6,6′-oxybis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates) IVa and IVb. The yields of compounds ІІІa-IIId, VIa-VId, and IVa, IVb were 57-70, 39-69, and 24-49%. respectively. The reactions of compounds Ia and Ib with diamines Va and Vb at a ratio of 2 : 1 led to the formation of the corresponding diethyl 6,6′-[ethane-1,2-diyl(or propane-1,3-diyl)diimino]bis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates) VIIa-VIId (Scheme 1). Dihydropyridine Ia reacted with butane-1,4-diamine (Vc) to give 6,6′-(butane-1,4-diyldiimino)bis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylate) (VIIe) as the only product even when the amount of diamine Vc was 3 ...