Synthesis of 1,5‐Disubstituted Tetrazole−Indolizine Bis‐Heterocycles and Their Copper (II) Recognizing Properties

Abstract

A novel bis‐heterocyclic system encompassing the 1,2‐dihydro‐3H‐pyrrolo[3,4‐b]indolizin‐3‐one and 1,5‐disubstituted tetrazole moieties was designed, synthesized, and evaluated as a Copper (II) recognizing agent. This was achieved by exploiting the optical characteristics of indolizine and the copper recognizing activity of tetrazoles. For the preparation of these compounds, a novel and simple synthetic strategy consisting in a double one‐pot process involving four‐step reactions was developed. The first process is a one‐pot five component reaction by using propargylamine as a bifunctional reactant to access the key intermediate, the N‐acylated tetrazole. Consequently, N‐acylated tetrazole was subjected to a one‐pot three component reaction, consisting in a bimolecular nucleophilic substitution followed of a domino process to afford the target compounds. The photophysical properties of the obtained bis‐heterocycles were evaluated against copper (II) addition.

The Semi-Synthesis of Imidazo-5α-Hydroxyvouacapane from Caesalpinia pulcherrima via a Groebke–Blackburn–Bienaymé Reaction

“…Among these species, Caesalpinia pulcherrima, a small tropical tree commonly used as an ornamental plant [9], has yielded metabolites with documented cytotoxic, antituberculosis, antibacterial, and antifungal properties. Isovouacapenol C 1 [10], pulcherrimin C 2 [11], pulcherrimin A 3 [12], 8,9,11,14-didehydrovouacapen-5α-ol 4, and 5α-hydroxyvouacapane 5 [10] are some of the metabolites isolated in this species, the latter being the natural product under study in this work (Figure 1).…”

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

“…By replacing the carboxylic acid with a nucleophilic azide reagent XN 3 (generally TMSN 3 ), the Ugiazide four-component reaction (UA-4CR) of an aldehyde, amine, isocyanide, and azide gives 1,5-disubstituted 1H-tetrazoles (1,5-DS-1H-Ts) B. The performance of post-condensation reactions of UA-4CR adducts has resulted in various 1,5-DS-1H-Ts containing heterocyclic compounds [28][29][30][31][32], such as bis-heterocyclic lactam-tetrazoles [33,34], 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines [35], ketopiperazinetetrazoles [36], imidazotetrazolodiazepinones [37], tetracyclic tetrazolylpyridoimidazoquinolines [38], bis-heterocyclic 1,5-disubstituted tetrazoleindolizines [39] and (E)-12-tetrazolyl-5Hquinazolino [3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give fused imidazotetrazolodiazepinones (Scheme 2A) [37].…”

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

“…By replacing the carboxylic acid with a nucleophilic azide reagent XN3 (generally TMSN3), the Ugiazide four-component reaction (UA-4CR) of aldehyde, amine, isocyanide, and azide gives 1,5disubstituted 1H-tetrazoles (1,5-DS-1H-Ts) B. The performance of post-condensation reaction of UA-4CR adducts has resulted various 1,5-DS-1H-Ts containing heterocyclic compounds [28][29][30][31][32], such as bis-heterocyclic lactam-tetrazoles [33,34], 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines [35], ketopiperazines-tetrazoles [36], imidazo-tetrazolodiazepinones [37], tetracyclic tetrazolyl pyridoimidazo quinolines [38], bis-heterocyclic 1,5-disubstituted tetrazole-indolizine [39] and (E)-12tetrazolyl-5H-quinazolino[3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give fused imidazo-tetrazolodiazepinones (Scheme 2, A) [37].…”