Facile and Regioselective Synthesis of Substituted 1H‐Pyrazolo[3,4‐b]quinolines from 2‐Fluorobenzaldehydes and 1H‐Pyrazol‐5‐amines

Abstract

The present article concerns the scope and limitations of the regioselective condensation of 2‐fluorobenzaldehydes with 1H‐pyrazol‐5‐amines, leading to the synthesis of substituted 1H‐pyrazolo[3,4‐b]quinolines (PQ), in the presence of a base catalyst (DABCO and 2,4,6‐trimethylpyridine). A method to obtain these nitrogen heterocycles with fluorine or trifluoromethyl substituents in different positions in the carbocyclic ring was developed as a part of a systematic research on the influence of fluorine‐containing substituents on the parameters of PQ. Those compounds, characterized by high‐fluorescence intensity, have been tested as emitters for the organic light‐emitting diodes since 1997. The functionalization of PQ causes changes in various parameters, for example, HOMO and LUMO levels, which are important for the adjustment of fabricated organic light‐emitting diodes. One of the easiest methods of PQ preparation, namely, the condensation of substituted anilines with 5‐chloro‐1H‐pyrazole‐4‐carbaldehydes, is not regioselective. The method described in this study allows synthesizing of 1H‐pyrazolo[3,4‐b]quinolines with good yields and high selectivity – only the expected isomer is obtained. As various different 2‐fluorobenzaldehydes are commercially available, and 1H‐pyrazol‐5‐amines with different substituents are easy to prepare, the method could be a good alternative to the already known procedures. All possible mechanisms of the reaction were also thoroughly studied.

Efficient Domino Strategy for the Synthesis of Substituted Bipyrazole Derivatives

“…On the basis of literature reports [21e, 22a, d] and our experimental results, a possible mechanism for the formation of compound 3 was proposed and is depicted in Scheme . The competing reaction between 3‐methyl‐1‐phenyl‐1 H ‐pyrazol‐5‐amine 1 and aldehyde occurs to generate intermediate A , which favors the following coordination and reaction in the presence of Y(OTf) 3 .…”

“…To study the scope of this methodology, isatin ( 4 ) was submitted to react with 3‐methyl‐1‐phenyl‐1 H ‐pyrazol‐5‐amine ( 1 ) under the same conditions. Unfortunately, the corresponding goal product ( 5 ) was not obtained under similar reaction conditions, probably because of the low reactivity or large steric hindrance of isatin [21e]. Then, to further explore the possibility of the multicomponent domino reaction, we used 1,3‐dimethyl‐1 H ‐pyrazol‐5‐amine to replace 3‐methyl‐1‐phenyl‐1 H ‐pyrazol‐5‐amine to investigate the possibility of the domino reaction.…”

“…Thus, the development of new strategy for these compounds has attracted considerable attention. A diversity of pyrazole and bipyrazole derivatives has been synthesized using different starting materials by various methods .…”

Organocatalyzed Synthesis of Functionalized Quinolines

“…In 2017, 1H-Pyrazol-5-aminesw ere used forg aining substituted 1H-pyrazolo [3,4-b] quinoline derivatives in the presence of DABCOb yS zlachcic et al [54] (Scheme 36). The regioselective protocoliss imple with abit low product yield.…”

“…In 2017, 1H‐Pyrazol‐5‐amines were used for gaining substituted 1H‐pyrazolo [3,4‐b] quinoline derivatives in the presence of DABCO by Szlachcic et al . (Scheme ).…”