C4-C5 fused pyrazol-3-amines: when the degree of unsaturation and electronic characteristics of the fused ring controls regioselectivity in Ullmann and acylation reactions

Pyrazol-3-amine is a scaffold present in a large number of compounds with a wide range of biological activities and, in many cases, the heterocycle is C4-C5 fused to a second ring. Among the different reactions used for the decoration of the pyrazole ring, Ullmann and acylation have been widely appl...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Organic & biomolecular chemistry 2020-07, Vol.18 (27), p.5145-5156
Hauptverfasser: Bou-Petit, Elisabeth, Plans, Arnau, Rodríguez-Picazo, Nieves, Torres-Coll, Antoni, Puigjaner, Cristina, Font-Bardia, Mercè, Teixidó, Jordi, Ramon y Cajal, Santiago, Estrada-Tejedor, Roger, Borrell, José I
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Pyrazol-3-amine is a scaffold present in a large number of compounds with a wide range of biological activities and, in many cases, the heterocycle is C4-C5 fused to a second ring. Among the different reactions used for the decoration of the pyrazole ring, Ullmann and acylation have been widely applied. However, there is some confusion in the literature regarding the regioselectivity of such reactions (substitution at N1 or N2 of the pyrazole ring) and no predictive rule has been so far established. As a part of our work on 3-amino-pyrazolo[3,4- b ]pyridones 13 , we have studied the regioselectivity of such reactions in different C4-C5 fused pyrazol-3-amines. As a rule of thumb, the Ullmann and acylation reactions take place, predominantly, at the NH and non-protonated nitrogen atom of the pyrazole ring respectively, of the most stable initial tautomer (1H- or 2H-pyrazole), which can be easily predicted by using DFT calculations. The regioselectivity of Ullmann and acylation reactions of C4-C5 fused pyrazol-3-amines is predicted using DFT calculations of the most stable tautomer (1 H - or 2 H -pyrazole) and occur, mainly, at the NH and non-protonated nitrogen atom, respectively.
ISSN:1477-0520
1477-0539
DOI:10.1039/d0ob00796j