The CIP (Cahn-Ingold-Prelog) priority rules are used to assign R and S labels to stereocentres. However it is known to be very prone to mis-implementation:
The CIP System Again:? Respecting Hierarchies Is Always a Must
Through our work on OEChem, OPSIN and Centres we have independently written 3 different CIP implementations and hence discussion of the corner cases of CIP inevitable becomes a heated coffee time discussion.
This deceptively simple case on the right turns out to give different results in many implementations.
Which “ligand” do you think has highest priority?
If you said [CH2][OH] you’d be right, but the majority of implementations disagree:
|CACTVS (Web Sketcher)||R [updated 23/02/2015]|
|AccelrysDraw 4.2||S (now R in BIOVIA Draw 2017)|
We can speculate that the cause of the disagreement may be that the left and right side of the molecule are symmetrical by atomic number (rule 1) and that hence rule 2 (atomic mass) is then being erroneously applied to ALL ligands… while correct implementations will only apply rule 2 to split the tie between the two ligands that could not be determined by rule 1 (*). Hence this case should be assigned R.
* “precedence (priority) of an atom in a group established by a rule
does not change on application of a subsequent rule.” (IUPAC recommendations)