One-Pot, Three-Component Approach to the Synthesis of 3,4,5-Trisubstituted Pyrazoles

Abstract

An operationally simple and high yielding protocol for the synthesis of polyfunctional pyrazoles has been developed through one-pot, three-component coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3-dipolar cycloaddition, and transition metal-free oxidative aromatization reaction sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component individually.

One‐Pot Synthesis of 2,3,5‐Trisubstituted Thiophenes through Three‐Component Assembly of Arylacetaldehydes, Elemental Sulfur, and 1,3‐Dicarbonyls

“…Based on the experimental results above, we proposed a plausible reaction pathway for the three‐component formation of thiophenes (Scheme ). The base‐promoted condensation of dicarbonyls and acetaldehydes generates the β,γ‐unsaturated diketone A . The deprotonation of A delivers the anion intermediate B , which undergoes a nucleophilic attack to sulfur S n to afford the intermediate C (Willgerodt−Kindler‐type reactions) .…”

Application of Photoclick Chemistry for the Synthesis of Pyrazoles via 1,3‐Dipolar Cycloaddition between Alkynes and Nitrilimines Generated In Situ

“…Despite the overall efficiency of this method, it usually requires the use of expensive metal catalysts and/or hazardous hydrazine derivatives, and suffers from limitations with respect to the substrate scope, regioselectivity and yield. To overcome these drawbacks, research was performed over the last decade through exploration of this multicomponent condensation reaction by modifying and optimizing the reactants and the reaction conditions to access pyrazole ring derivatives . More recently and in a more atom‐economic fashion, catalytic procedures have been published.…”

Luxury of N‐Tosylhydrazones in Transition‐Metal‐Free Transformations

“…This metal‐ and solvent‐free approach delivered the pyrazoles in moderate to good yields at ambient temperature. Other compounds such as azides, electron‐deficient alkenes (derived from aldehyde and 1,3 diketones) and gem ‐dibromoethenes also served as reaction partners.…”