Yield, Conversion and Selectivity
Considers limiting reactant and product
  • High yield is desirable
  • If yield is low but conversion is high- reaction requires optimisation
  • If yield is low and conversion is low- reaction requires redesign
Yield is high Yield low but selectivity high (low conversion) Yield low and selectivity low (high conversion)
✔ Reaction can be optimised You need to return to your reaction and redesign it
Atom economy
Considers all reactants
Assumes 100% yield
  •  Atom Economy (AE) measures the efficiency of the reaction by the number of the atoms from the reactants that appear in the final product.
  • AE assumes 100% yield and stoichiometric loading
  • AE is an excellent metric to access the inherent efficiency of a reaction with respect to use of reactants- however is not great as a standalone metric
Atom economy high (≥ 62%) Atom economy low
✔ Maximise incorporation of starting material into product (fewer wasted atoms).
Choose leaving groups to be as small as possible, avoid large protecting groups..
Reaction mass efficiency
Considers all reactants, stoichiometries and yield
The most efficient your reaction can be is if RME=AE
  • Reaction Mass Efficiency (RME) gives a fuller picture of reactant use. It is mass based and incorporates yield and stoichiometry
  • According to Andraos[citeneeded]: a reaction is only considered green when both the AE and RME are above 62%. In other words, if a reaction has an RME of ≥62% but an AE ≤62%, or vice versa, the reaction is not green.
  • However, if your AE and RME are much greater than the current state of the art, then you are well on your way to improving the green credentials of such transformations.
  • The AE provides the optimum efficiency your process can achieve; the closer the RME is to it, the closer the reaction is to its optimal efficiency.
RME (≥62%) ~ AE RME << AE
✔ Try to reduce stoichiometric loading of reagents whilst monitoring yield
Solvents
  • At reaction discovery stage is clearly important to allow for screening for as broad a range of solvents as possible
  • This will help determine the best solvent and best solvent properties for the reaction
  • Which will come in handy if the optimum solvent you have selected for the reaction is highly undesirable- restricted by OPRD and REACH- which will give you a red a flag
  • In this situation, use of solvent maps could help you find a greener solvent alternative to screen for.
No highly undesirable solvents Black listed solvents used
✔ Do not use! Use CHEM21 solvent replacement guides to identify a potential replacement
Health and safety
Red-flagged substances carry a serious physical, health or environmental risk
  • Screening for a broad range of reagents is also necessary at this stage and give a lot of insight into the chemical transformation
  • As such only the most severe hazard statements (red flag) are to be avoided at zero pass and must be substituted
No red flag Red flag
✔ Use reagent replacement guides to identify a potential replacement
If not possible, must be justified!