This paper presents a simplified approach for the application of material efficiency metrics to linear and convergent synthesis plans encountered in organic synthesis courses. Computations are facilitated and automated using intuitively designed Microsoft Excel spreadsheets without invoking abstract mathematical formulas. The merits of this approach include (a) direct application of green chemistry principles to synthesis planning; (b) strongly linking green metrics calculations and synthesis strategy; (c) pinpoint identification of strengths and weaknesses of any synthesis plan's material efficiency performance using effective visual aids; (d) in-depth quantitative and qualitative critiquing of synthesis plan performance and strategy; and (e) giving opportunities to students to offer insightful suggestions to improve or "green up" published procedures based on their growing personal database of chemical reactions as they continue their education in chemistry. An extensive database of over 600 examples taken from Organic Syntheses was created as a repository of reliable examples that instructors can draw upon to create meaningful classroom pedagogical exercises and homework problem sets that couple material efficiency green metrics analyses and traditional learning of organic chemistry.
A series of pedagogical problem set exercises are posed that illustrate the principles behind material efficiency green metrics and their application in developing a deeper understanding of reaction and synthesis plan analysis and strategies to optimize them. Rigorous, yet simple, mathematical proofs are given for some of the fundamental concepts, particularly how metrics for overall plan material performance are related to their composite counterparts for individual reactions. Throughout this exposition, whenever a synthesis scheme is examined, it is converted into a compact tree diagram that is used to depict plans of any degree of complexity (linear or convergent) as a means to conveniently keep track of all reagents, intermediates, reaction yields, stoichiometric coefficients, number of branches, number of reaction steps, and convergent steps. We demonstrate that such tree diagrams facilitate the computation of material efficiency metrics for any individual reaction in a plan as well as for the entire plan. We also show how such diagrams may be used to plan schedules for reaction operations when multiple linear branches are run concurrently. For brevity the Supporting Information contains full solutions to posed problems. ■ INTRODUCTIONFollowing the previous paper, 1 which highlighted the computation of kernel and complete material efficiency metrics for synthesis plans based on mass balances using intuitive spreadsheets, we now present key insights about reaction and synthesis plan analysis. We remind the reader that the term "kernel" signifies that associated metrics parameters do not include auxiliary materials and the term "complete" signifies that they do. These insights are best understood after working through posed problem set questions that can also be used in classroom and laboratory settings when teaching green chemistry principles. Some problems are theoretically based and involve abstract thinking; however, all problems are grounded in concrete examples taken from the literature. The structure of the paper is as follows. We begin with a pedagogically useful representation of traditional synthesis schemes by means of a tree diagram 2 that depicts them compactly to facilitate the computation of fundamental material efficiency metrics such as reaction yields (RY), atom economy (AE), global reaction mass efficiency (gRME), and process mass intensity (PMI). We assume from the outset that all chemical equations in any given synthesis scheme are appropriately balanced. These parameters may be determined directly by tracing the connectivity between intermediates and their progenitor reagents in each synthesis tree branch of a given plan. This allows for easy determination of basic material efficiency green metrics performances for individual reactions and for the entire plan, thus avoiding tedious tracking tasks. The tree diagram also guides the construction of the SYNTHESIS spreadsheet discussed in the previous paper, 1 particularly for convergent synthesis plans composed of multiple branches. Moreover,...
In this paper, we analyze six published algorithms that evaluate environmental and hazard impact green metrics. The methods are compared and contrasted on a common set of chemical reactions and synthesis plans. The relative greenness of four reaction procedures to prepare iron(II)oxalate dihydrate and three industrial preparations of aniline are examined. We also examine the organic syntheses preparations of 2,2-diethoxy-1-isocyanoethane, thiete 1,1-dioxide, and ethyl phenylcyanopyruvate that we previously evaluated by material efficiency. We discuss the merits and limitations of all algorithms with respect to quality of calculation outputs, visualization, and ease of use.
This chapter provides an overview of green metrics and their historical role in promoting the development of green chemistry. Starting with the history of the field, the Twelve Principles of Green Chemistry are introduced and discussed in conjunction with a "green-by-design" approach recently applied to the synthesis of Lipitor ® . Various perspectives on synthetic efficiency are briefly outlined with reference to atom economy and E factor. These ideas are further explored in the context of three industrial processes which have received Presidential Green Chemistry Challenge Awards. The synthesis of ibuprofen is examined from the point of view of intrinsic efficiency. Using the BHC process as an example, several benefits associated with the use of catalysis are discussed, with an emphasis placed on designing atom-efficient reactions. A global perspective centered around the production of chemical waste is also outlined with reference to Merck's commercial synthesis of Januvia ® , a medication for the treatment of type II diabetes. Finally, Pfizer's new sertraline process is used to describe ways of improving both quantitative as well as qualitative aspects of an industrial synthesis. The chapter concludes with a brief outline of the future directions of green metrics.
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