On the Probability That Ring-Forming Multicomponent Reactions Are Intrinsically Green: Setting Thresholds for Intrinsic Greenness Based on Design Strategy and Experimental Reaction Performance

Abstract

This paper describes in detail the determination of the likelihood that a given generalized chemical reaction may be considered intrinsically “green” based on design strategy. Justification is given for setting threshold constraints on reaction yield and kernel reaction mass efficiency (RME) performances at greater than 80% and greater than 61.8%, respectively, for intrinsically green reactions. These criteria are applied to a survey of 60 named ring-forming multicomponent reactions (MCRs) and 2000+ such reactions reported in the literature from 2003 to 2011. Patterns among various ring construction motifs are discussed. Results show that 5- and 6-membered monocyclic rings are most commonly made by [2+2+1] and [3+2+1] cycloadditions where 57% and 76% of them, respectively, have a 100% chance of being intrinsically green from a design perspective. Similarly, the [4.3.0] and [4.4.0] skeletons are the most common fused bicyclic structures made by MCR strategies where 38% and 59% of them, respectively, have a 100% chance of being intrinsically green. The syntheses of various heterocyclic ring structures made by MCRs have also been surveyed using this new criterion. The application of this probability analysis is also demonstrated for the total synthesis of ring containing scaffold structures of praziquantel and frondosin B, two compounds of pharmaceutical interest made using MCRs. The direction of future research in MCR development is also briefly discussed.

Towards automation of chemical process route selection based on data mining

“…Green Chemistry unnecessary changes of the oxidation state may lead to significant environmental impacts. 7,50,51 To track changes in the oxidation state the set of atoms involved in the target bondforming reactions across a route is determined. The oxidation state of each of those atoms is then calculated at each reaction step as described in ref.…”

Sustainable Synthesis of Pseudopeptides via Isocyanide-Based Multicomponent Reactions in Water

“…Sustainability science and sustainability originated from sustainable development and environmental science concepts . In chemistry, it is a scientific concept that seeks to improve the efficiency of using natural resources to meet human needs without compromising the requirements of future generations .…”

“…Sustainability science and sustainability originated from sustainable development and environmental science concepts. 1 In chemistry, it is a scientific concept that seeks to improve the efficiency of using natural resources to meet human needs without compromising the requirements of future generations. 2 Sustainable chemistry involves designing, constructing, and using efficient, effective, safe, and more environmentally benign chemical processes and products.…”

Ultrasound-Assisted One Pot Synthesis of Novel 5-(1-(Substituted phenyl)-4,5-diphenyl-1H-imidazol-2-yl)-4-methylthiazole

“…MCRs on numerous occasions are an effective alternative to multistep sequential synthesis for instance, they show a high degree of atom efficiency as the maximum if not all of the atoms of the starting reactants are transformed in to the product [12,13]. They are convergent as a number of starting reactants combine in one step reaction to form the target molecules, they are having a higher degree of efficiency since the product formation takes place in one-step, in place of multiple sequential steps, bond formation between several atoms other than hydrogen atoms takes place in one synthetic step, therefore they display extremely high bondforming-index (BFI) [14][15][16][17][18].There is still a need of general awareness among synthetic chemists that MCRs are undeniably able to deal with delicate chemical problems in an environmentally friendly manner. This work thus aims to explore the scope and opportunities which the utilization of MCRs can bring to eco-friendly green synthesis and process design.…”