By exploiting the combined use of a heterogeneous recyclable palladium(II)-bis(N-heterocyclic carbene)catalyst and cyclopentyl methyl ether(CPME)as a convenient recoverable safer reaction medium,an effective wastemini...By exploiting the combined use of a heterogeneous recyclable palladium(II)-bis(N-heterocyclic carbene)catalyst and cyclopentyl methyl ether(CPME)as a convenient recoverable safer reaction medium,an effective wasteminimized approach has been developed for the intramolecular Pd-catalyzed C(sp3)-H activation of methyl pyrrole derivatives.This synthetic tools has allowed to access condensed N-heterocycles generally endowed with biological activities and representatively are the core motif of complex molecules such as Mitomycines and Tylophorines.The heterogeneous catalytic system could be recovered and reused up to representative five runs without any loss in efficiency.The target products(19 examples)have been obtained selectively and with excellent isolated yields up to 93%.The approach leads to the definition of a protocol with a very good E-factor(21)which is much lower(up to 98%)than those of comparable literature examples.Other green metrics have been calculated and the data collected demonstrate that our newly developed protocol is very promising in terms of its environmental impact profile.展开更多
Metal contamination is a waste-generating and serious issue in the synthesis of chemicals,in particular in the case of products with biological activity.The appropriate selection of operating conditions plays a crucia...Metal contamination is a waste-generating and serious issue in the synthesis of chemicals,in particular in the case of products with biological activity.The appropriate selection of operating conditions plays a crucial role in the abatement of metal leaching in solution and associated wastes.Herein we report a waste-minimized continuous flow process for the synthesis of 1,4-disubstitutedβ-keto 1,2,3-triazoles exploiting the use of a copper tube flow reactor(CTFR).The selection of the proper azeotropic mixture allowed an almost quantitative recovery of the reaction medium greatly influencing the E-factor of the protocol.A thorough understanding of the main parameters affecting the waste generation was given by calculation of the E-factor distribution for different work-up tested under batch and flow conditions.Furthermore,the measurement of different green metrics(AE:Atom Economy,SF:Stoichiometric Factor,RME:Reaction Mass Efficiency,and MRP:Mass Recover Parameter)clearly demonstrated the benefits of the flow scale-up that allowed to perform a low environmental footprint CuAAC reaction.展开更多
基金funded by the European Union-NextGenerationEU under the Italian Ministry of University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY.
文摘By exploiting the combined use of a heterogeneous recyclable palladium(II)-bis(N-heterocyclic carbene)catalyst and cyclopentyl methyl ether(CPME)as a convenient recoverable safer reaction medium,an effective wasteminimized approach has been developed for the intramolecular Pd-catalyzed C(sp3)-H activation of methyl pyrrole derivatives.This synthetic tools has allowed to access condensed N-heterocycles generally endowed with biological activities and representatively are the core motif of complex molecules such as Mitomycines and Tylophorines.The heterogeneous catalytic system could be recovered and reused up to representative five runs without any loss in efficiency.The target products(19 examples)have been obtained selectively and with excellent isolated yields up to 93%.The approach leads to the definition of a protocol with a very good E-factor(21)which is much lower(up to 98%)than those of comparable literature examples.Other green metrics have been calculated and the data collected demonstrate that our newly developed protocol is very promising in terms of its environmental impact profile.
基金support to the project AMIS,through the program“Dipartimenti di Eccellenza-2018-2022”.
文摘Metal contamination is a waste-generating and serious issue in the synthesis of chemicals,in particular in the case of products with biological activity.The appropriate selection of operating conditions plays a crucial role in the abatement of metal leaching in solution and associated wastes.Herein we report a waste-minimized continuous flow process for the synthesis of 1,4-disubstitutedβ-keto 1,2,3-triazoles exploiting the use of a copper tube flow reactor(CTFR).The selection of the proper azeotropic mixture allowed an almost quantitative recovery of the reaction medium greatly influencing the E-factor of the protocol.A thorough understanding of the main parameters affecting the waste generation was given by calculation of the E-factor distribution for different work-up tested under batch and flow conditions.Furthermore,the measurement of different green metrics(AE:Atom Economy,SF:Stoichiometric Factor,RME:Reaction Mass Efficiency,and MRP:Mass Recover Parameter)clearly demonstrated the benefits of the flow scale-up that allowed to perform a low environmental footprint CuAAC reaction.