Biomass Waste-Derived Pd–PiNe Catalyst for the Continuous-Flow Copper-Free Sonogashira Reaction in a CPME–Water Azeotropic Mixture

Francesco Ferlin,Federica Valentini,Luigi Vaccaro,Elena Petricci,Daniele Sciosci,Massimo Calamante

doi:10.1021/acssuschemeng.1c03634

Abstract

Herein, we report on the development of a waste minimization/valorization methodology applied to the representative benchmark Sonogashira cross-coupling reaction performed in a continuous-flow reactor, featuring a continuous-flow downstream membrane organic/aqueous separator to recover medium and products with minimal waste. The protocol is based on the use of a biomass waste-derived heterogeneous Pd-based catalyst, which is obtained from the valorization of urban-waste pine needles (PiNe). In a circular economy approach, the PiNe biomass has been proven to be capable of producing an effective active carbon support for Pd nanoparticle immobilization. In addition, the catalyst has been utilized in an azeotropic mixture formed by industrial waste-derived cyclopentyl methyl ether (CPME) and water. Thanks to this combination and with the adoption of flow conditions, high yields of final target products could be accessed with high stability and durability of the catalyst. Final isolation of the products has been realized by setting an in-line liquid–liquid separator in flow, which has also allowed CPME recovery with a significant reduction of the waste generated. The protocol has been applied to the representative preparation of eniluracil, a GSK API.

Highlights

Sonogashira cross-coupling is a widely useful synthetic tool allowing the introduction of an acetylenic moiety in a variety of molecular structures.[1−4] Since the seminal work by Sonogashira and Hagihara,[5] the protocol has been largely studied and improved by exploiting the use of inorganic or organic bases under homogeneous or heterogeneous conditions and in the presence of a wide range of reaction media.[6−15]Among the metal catalysts, palladium is arguably the preferred choice for the promotion of Sonogashira crosscoupling reactions
Our research program aims at developing efficient metal heterogeneous catalytic systems,[18−21] while we are contributing to a circular economy approach working on biomass valorization.[22−25] Recently, we dedicated our attention to the valorization of urban waste and exploited biochar derived from local biomass as a viable alternative to carbonaceous supports for the preparation of Pd-based heterogeneous catalysts
We report our results on the exploration of a local biomass urban waste material to design and develop an effective palladium catalytic system and combine its use with the safe solvent cyclopentyl methyl ether (CPME) derived from industrial waste aiming at implementing the “circular economy” approach into the definition of sustainable synthetic tools (Scheme 1)

Summary

■ INTRODUCTION

Sonogashira cross-coupling is a widely useful synthetic tool allowing the introduction of an acetylenic moiety in a variety of molecular structures.[1−4] Since the seminal work by Sonogashira and Hagihara,[5] the protocol has been largely studied and improved by exploiting the use of inorganic or organic bases under homogeneous or heterogeneous conditions and in the presence of a wide range of reaction media.[6−15]. We report our results on the exploration of a local biomass urban waste material (pine needle) to design and develop an effective palladium catalytic system and combine its use with the safe solvent CPME derived from industrial waste aiming at implementing the “circular economy” approach into the definition of sustainable synthetic tools (Scheme 1). Considering that the Sonogashira reaction is a mature synthetic tool and aiming at optimizing the sustainability of this reaction under the umbrella of a circular economy, waste minimization approach, and sustainability approaches, we preferred to focus on iodides and the production of a very cheap and efficient catalyst system utilizing an effective and recoverable medium To this aim, we have set a continuous-flow reactor protocol allowing a multigram-scale production to optimize the recovery and reuse of both the catalytic system and reaction medium and to minimize the waste produced.[61−65]

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES