Thermal Cyclization of (2-Ethynylphenyl)triazenes:  Facile Synthesis of Substituted Cinnolines and Isoindazoles

Abstract

High-temperature intramolecular cyclization of N, N-dialkyl-N'-(4-substituted-2-ethynylphenyl)triazenes provides under neutral conditions both 6-substituted cinnolines and 5-substituted isoindazoles in moderate to excellent yields.

Triazenes: A Versatile Tool in Organic Synthesis

“…A typical example is the synthesis of 1 from aniline and dimethylamine 21. The reaction conditions are surprisingly tolerant of a wide range of functional groups, including ester, halogen, and nitrile functionalities 22, 23. Aryl systems other than those derived from aniline have been used to make dimethylaryl triazenes for antitumor study, the most active and well‐studied of which is 5‐(3,3‐dimethyltriazeno)imidazole‐4‐carboxamide ( 2 , Scheme ),24 also known as dacarbazine.…”

“…A new method for the generation of cinnolines as well as isoindazoles from aryl triazene moieties ortho to alkyne functionalities was recently developed by Haley and co‐workers 22. Heating the 1‐(2‐ethynylphenyl)‐3,3‐diethyltriazenes 14 (Scheme ) to 170–180 °C in 1,2‐dichlorobenzene gave a mixture of isoindazole 15 and cinnoline 16 products.…”

Methods for the synthesis of cinnolines (review)

“…Another example of the cyclization of ortho-ethynyl-substituted triazines by heating the compounds in ortho-dichlorobenzene was described in Kimball's papers [85][86][87][88][89]. Initially, on heating to 170°C a mixture of products was obtained -the isoindazole 22 and cinnoline 23 in a ratio of 1:1 (Scheme 26).…”

Triazene: vielseitige Verbindungen für die organische Synthese

“…[2, 12±15] Die Ergebnisse verschiedener Forschergruppen belegen enzymkatalysierte Demethylierung als ersten Schritt des Metabolismus, woran sich Umlagerung des disubstituierten Triazens und proteolytische Abspaltung von Anilin unter Bildung des Methyldiazoniumions anschlie˚en (Schema 2). [22,23] Auch Dimethylaryltriazene mit nicht von Anilin abgeleiteten aromatischen Substituenten wurden in Antitumor-Studien getestet. [14,15,20] Dialkylphenyltriazene mit diesem Substitutionsmuster werden gewˆhnlich aus den Anilin-Derivaten und sekund‰ren Aminen hergestellt, so 1-Phenyl-3,3-dimethyltriazen 1 als typisches Beispiel aus Anilin und Dimethylamin.…”