Atomic greenness metrics

At least one of the 12 principles—number 2, design safe products—is a must for pharmaceutical synthesis. Indeed, pharmaceutical products are regulated and tested for safety. Principle number 7, maximize atom economy, refers to a metric against which the greenness of a process may be evaluated. Green metrics are covered in the next section. 

Barry Trost of Stanford University published the first formal green metric in 1991 in Science. Trost s idea, atom economy, measures the percentage ratio of the total mass of the products to starting materials (Equation 13.2).26... 

Shortly after Trost introduced the idea of atom economy, Roger Sheldon of Delft University of Technology in the Netherlands reported another green metric called E-factor.30 31 E-Factor is the ratio of the mass of the total waste from a process to the mass of the product generated in that same process (Equation 13.5). 

Solvents are not included in the calculation. Like effective mass yield, carbon efficiency strives to make a value judgment on the relative importance of various wastes. Elimination of water from a molecule would not count against the carbon efficiency of a reaction, but it would give a decreased atom economy. By not including all wastes, carbon efficiency is not as strict as most green metrics. Of course, all metrics have their shortcomings and carry their own assumptions. 

Green Metrics Atom Economy is Not the Whole Story... 

Quantitative evaluation of chemical processes in terms of environmental impact and eco-friendliness has gradually become a topic of great interest since the original introduction of the atom economy (AE) by Trost [1], and the E-factor by Sheldon [2]. Since then, other indexes have been proposed for the green metrics of chemical processes, such as effective mass yield (EMY) [3], reaction mass efficiency (RME) [4] and mass intensity (MI) [5], along with unification efforts [6, 7] and comparisons among these indexes [8]. 

These figures clearly show how a greenness evaluation of a process based only on "visual inspection of synthetic schemes can be misleading a very large part of the waste comes from isolation steps, which do not appear in synthetic schemes. Moreover, some green metrics, such as atom economy do not consider at all this portion of waste. 

Two further points deserve comment. First, in practice, the two types of materialization (reagents vs. auxiliary materials) are not independent, for instance, decreasing the volume of the solvent used as reaction mean, to decrease the E-factor, may affect the yield of the reaction, and change the value of RME. Second, while the evaluation of the atomic greenness involves two metrics, the materialization via auxiliary materials is assessed by one only, the E-factor (or MI), because there is no theoretical upper limit for the amount of matter used in them (for the atomic greenness, the stoichiometric equation defines AE as such a limit). This situation makes difficult the comparison of auxiliary materials responsible for materialization in different reactions and, consequently, of their global materialization, because it is impossible to define a normalized scale for the E-factor (or MI). This is a... 

Yield and other mass-related metrics such as atom economy, reaction mass efficiency and mass intensity have been examined by Constable et al with regard to their significance concerning greenness and costs. The importance of using a (product) concentration term, which can be mass intensity or mass index, is additionally emphasized by Laird et al This is in compliance with Winterton, who in his twelve more green chemistry principles demands the establishment of full mass balances. 

Because RME accounts for the mass of all reactants, that is, the actual stoichiometric quantities used, and therefore includes yield and atom economy, this combined metric is probably one of the most helpful metrics for chemists to focus attention on how far from green their current processes actually is. However, like many green chemistry metrics, it does take a little bit of thought to calculate in practice, as one has to work to strict definitions of what to include and what to exclude [46] ... 

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