Design and Synthesis of Pyrrolotriazepine Derivatives: An Experimental and Computational Study

Abstract

The pyrrole derivatives having carbonyl groups at the C-2 position were converted to N-propargyl pyrroles. The reaction of those compounds with hydrazine monohydrate resulted in the formation of 5H-pyrrolo[2,1-d][1,2,5]triazepine derivatives. The synthesis of these compounds was accomplished in three steps starting from pyrrole. On the other hand, attempted cyclization of a pyrrole ester substituted with a propargyl group at the nitrogen atom gave, unexpectedly, the six-membered cyclization product, 2-amino-3-methylpyrrolo[1,2-a]pyrazin-1(2H)-one as the major product. The expected cyclization product with a seven-membered ring, 4-methyl-2,3-dihydro-1H-pyrrolo[2,1-d][1,2,5]triazepin-1-one was formed as the minor product and was converted quantitatively to the major product. The formation mechanism of the products was investigated, and the results obtained were also supported by theoretical calculations.

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

“…Since the central carbon atom of an allene unit is more electropositive, the carbon atom can undergo an attack by the amide nitrogen atom to form a six-membered ring. In the case of 7a–c, the formation of allenic intermediates is out of question [15]. …”

“…White needles from chloroform, mp: 109–110 °C (Lit. [15] 105–106 °C); 1 H NMR (400 MHz, CDCl 3 ) δ 8.01 (d, J = 7.5 Hz, 2H, arom. ), 7.62 (t, J = 7.5 Hz, 1H, arom.…”

“…Recently, we developed new synthetic methodologies for the synthesis of various pyrrole-fused new heterocycles using alkyne cyclization reactions [15–22]. In this article, we demonstrate for the first time the concept of the cyclization of N- alkyne-substituted pyrrole esters 7 (Fig.…”

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

“…The propargyl ester 13 [44–46] was obtained in high yield from the reaction of 12 with propargyl bromide in the presence of NaH as a base (Scheme 2). Gold catalysis is an excellent method for constructing complex chemical architectures in a mild manner that would be difficult to achieve using other reactions [41,47–53].…”

Ionic Liquid Solvation versus Catalysis: Computational Insight from a Multisubstituted Imidazole Synthesis in [Et2NH2][HSO4]

“…Computational chemistry has become ap rime tool for detailed studies of reactionm echanisms and catalysis. [13] Herein, we provide answerst ot he above questions from ad etail mechanistic computational approach at the Kohn-Sham (KS) density functional theory (DFT) level.T he imidazole formation reactiono fS cheme 1i su sed as an example because of the very efficient conversion in the presence of the IL. We chose benzaldehyde among the array of aldehydes that were used in our experimental work, [6] because of its simple structure, along with other reagents, namely benzil, ethanolamine, ammonium acetate, and[ Et 2 NH 2 ][HSO 4 ], to conduct theoretical calculations on the reaction.…”