One-Pot Coupling–Coupling–Cyclocondensation Synthesis of Fluorescent Pyrazoles

Abstract

Consecutive four-component coupling-coupling-cyclocondensation syntheses of pyrazoles and pyrimidines were developed by taking advantage of the provisional, sequentially Pd-catalyzed one-pot generation of alkynones from aryl iodides, ethynylmagnesium bromide, and acid chlorides. This one-pot methodology allows the concise, diversity-oriented generation of a set of donor-, acceptor-, and donor-acceptor-substituted pyrazoles, which are interesting fluorophores. Most distinctly, donor-acceptor pyrazoles display remarkably red-shifted emission maxima and pronounced positive solvochromicity, spanning an overall range from 363 nm (cyclohexane) to 595 nm (acetonitrile). DFT and TD-DFT calculations elucidate the electronic structure and the photophysical behavior. Upon photonic excitation, considerable charge-transfer character becomes apparent, which rationalizes the origin of huge Stokes shifts and solvochromic behavior.

Fast and Efficient Continuous Flow Method for the Synthesis of Ynones and Pyrazoles

“…[15] Because of their wide biological activity, [16] the challenge remains to develop new synthetic routes for the rapid and regioselective [17] assembly of substituted pyrazoles from simple and readily available starting materials. [18] In this context, when compared with batch techniques, continuous flow chemistry has many attractive features: enhancing mass-and heat-transfer, minimizing reaction volumes, and improving the degrees of sample-and reagent-mixing. [19] Furthermore, the residence time in a microreactor can be controlled precisely to achieve the maximum yield and reaction-selectivity.…”

Using Calcium Carbide as an Acetylene Source for Cascade Synthesis of Pyrrolo[2,3‐b]quinoxalines via Copper‐Free Sonogashira Coupling Reaction

“…Novel protocols have already been developed for the synthesis of various functional molecules such as propargylamines, diarylethynes, triazoles, and enaminones from calcium carbide. The use of ethynylmagnesium bromide has also been reported recently as a commercial acetylene surrogate in the Kumada–Negishi ‐type coupling reactions . It was further demonstrated in these protocols that, unlike the traditional methods, multiple protection and de‐protection steps could be avoided with the direct usage of calcium carbide.…”

“…The use of ethynylmagnesium bromide has also been reported recently as a commercial acetylene surrogate in the Kumada-Negishi-type coupling reactions. [13] [14] It was further demonstrated in these protocols that, unlike the traditional methods, multiple protection and deprotection steps could be avoided with the direct usage of calcium carbide. This greatly reduced the number of synthetic steps, resulting in a more efficient and greener organic synthesis.…”

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

“…The pyrazole nucleus is a frequently occurring motif in many pharmaceuticals [1–2] and biologically active compounds [3–4], agrochemicals [5], dyes [6], fluorescent materials [7–8] and ligands of complexing agents [9–11]. Multiaryl-substituted pyrazoles are of special interest, with some drug molecules such as the nonsteroidal anti-inflammatory agent Lonazolac [12] or the well-known COX-2 inhibitor Celecoxib [13] as prominent representatives.…”