Mechanochemistry Enabled Construction of Isoxazole Skeleton via CuO Nanoparticles Catalyzed Intermolecular Dehydrohalogenative Annulation

Abstract

A dehydrohalogenative approach for isoxazole annulation by partnering β‐vinyl halides and α‐nitrocarbonyls under mechanochemical setting was accomplished. This chemistry is operative under the cooperative catalysis of cupric oxide nanoparticles (<50 nm) and DABCO. The key beneficial aspects of this protocol include: (i) broad substrate scope, (ii) no vigorous work‐up, (iii) short reaction time, (iv) solvent‐free condition, (v) commercial viability of substrates/reagents (vi) good chemical yields and selectivity. The other merit of this chemistry is the ease with which CuO can be recuperated and reused after the reaction with not much drop in catalytic activity for six runs. With no confinement to β‐vinyl halides, the validated condition is also open to alkynes for isoxazole preparation, thereby establishing the broader utility of the current methodology.

Step‐Economical Mechanosynthesis of Hybrid Azoles: Deciphering Their π‐Orbital and Pharmacological Characteristics

“…(i) Based on previous expertise in CuO nano-catalysis for click chemistry, [32,40] our investigation centered on CuO nanoparticles (> 50 nm) as catalyst. (ii) As our earlier studies revealed zirconia based planetary jar (45 mL) and balls (ø = 15 mm, 6 Nos) are compatible with CuO nano-catalytic processes, [32,33] we preferred the same ball-milling set-up. At the outset, equimolar proportion of 1 a, 2 a and 3 a along with 5 mol% of commercially available CuO nanoparticles were ball-milled for 60 min (entry 1).…”

“…As part of our synthetic efforts in bio-active heterocyclic cores, [24][25][26][27][28][29][30][31] we envisaged the preparation of mixed azoles by encompassing click chemistry and imination in a single pot operation. Based on our mechanochemical program for sustainable synthesis, [32][33][34][35][36][37] we were particularly interested in executing this idea under ballmilling conditions. It is pertinent to mention that our group has previously demonstrated the one-jar preparation of oxindoletriazole pharmacophores via mechanochemical merger of click and Baylis-Hillman chemistry under CuO nano-catalysis (Scheme 1, top).…”

Practical Coprecipitation Approach for High-Aspect Ratio Cupric Oxide Nanoparticles: A Sustainable Catalytic Platform for Huisgen and Fluorogenic Click Chemistry

“…In the aforementioned context, cupric oxides in various nanodimensions have been frequently encountered as a heterogeneous catalyst for triazolylation owing to their well-understood physicochemical properties, environmentally friendly appeal, and facile recyclability. − However, controlling the size and shape is a complicated combination of various interlinking factors such as steric confinements, temperature, and electrostatic interactions. Nevertheless, different modes of preparation for CuO nanomaterials have been documented, depending on which, the morphology and size can be fine-tuned. − In terms of simplicity, chemical coprecipitation is by far the most popular method, as it does not employ any reducing agents, support materials, or immobilizing agents. − With this background coupled with our pursuit on azide–alkyne cycloaddition by CuO-based nanocatalysis, − we herein report a simple synthesis of nanorod-like cupric oxide (referred throughout as CuO NRs) by adopting the coprecipitation strategy. Compared to other established procedures, our coprecipitation strategy enables the formation of CuO nanoparticles in high aspect ratio (Table ).…”