Relationships Between Step and Cumulative PMI and E-factors: Implications on Estimating Material Efficiency With Respect to Charting Synthesis Optimization Strategies

27 June 2018, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


This report describes mathematical relationships between step and cumulative process mass intensities (PMIs) for synthesis plans, and analogous parameters applied to Efactors. It is shown that both step E-factors and step PMIs are not additive for synthesis plans. It is also shown that a recursive calculation of cumulative PMIs from step PMIs is
a rapid method of determining overall PMIs for synthesis plans, though cumulative PMIs are not sufficiently informative as step PMIs or step E-factors to identify bottlenecks in
synthesis plans. Illustrations on the use of these metrics to track the material efficiency of published synthesis plans for the pharmaceutical, apixaban, are given as a template
example. Advantages and disadvantages of each metric are discussed. A general algorithm to select the most promising candidate synthesis plans considered at the design
stage for a given molecular target that most likely satisfy “green” material efficiency criteria is also presented.


green chemistry education
green chemistry engineering
sustainability metrics

Supplementary materials



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