3D stereochemistry: R/S and cis/trans

How to use it

Drag over the molecule to rotate it, and use the mouse wheel or pinch with two fingers to zoom. With the Atom tool, tap a hydrogen to replace it with the selected element: the program adds the missing hydrogens and rearranges the geometry. Bond turns a single bond into a double or triple one, or joins two atoms to close a ring. Invert swaps two substituents of a chiral center (R becomes S) or flips one end of a double bond (E becomes Z) without touching the rest of the molecule.

With Analyze, tap a chiral center or a double bond: the priorities 1 to 4 of its substituents appear, along with a button that turns the molecule so the lowest-priority group points away from you, which is exactly the view you need to assign R or S. If you untick “Show the answer”, the letters are hidden so you can practice before checking.

Cahn-Ingold-Prelog priority rules

To name the configuration of a stereocenter you first rank its four substituents. The CIP rules do it like this:

• Atomic number. The atom bonded directly to the center with the higher atomic number has the higher priority: Br > Cl > O > N > C > H.
• Tie-break by spheres. If two atoms are the same, compare the sets of atoms bonded to each one, sorted from highest to lowest. The first set with a higher atom wins; if they are still tied, move one sphere further out, always exploring the highest-priority branch first.
• Multiple bonds. A double bond counts as two single bonds: C=O is treated as a carbon bonded to two oxygens. That is why –CHO outranks –CH₂OH.

R or S

Once the priorities are assigned, look at the molecule with substituent 4 (almost always the hydrogen) pointing away from you. If the path 1 → 2 → 3 runs clockwise, the center is R (rectus); if it runs counterclockwise, it is S (sinister). The letter does not tell you which way polarized light is rotated: that is the (+) or (−) sign, which can only be measured.

A molecule with n chiral centers has at most 2ⁿ stereoisomers. There can be fewer if one of them is meso, like meso-tartaric acid: it has two centers, R and S, but an internal plane of symmetry makes it identical to its mirror image. Try it with the “Mirror image” button: the letters swap and the molecule is the same.

E/Z versus cis/trans

A C=C double bond cannot rotate, so its substituents stay fixed on one side or the other. Cis/trans naming compares two identical or equivalent groups: cis if they are on the same side, trans if they are on opposite sides. It works well for but-2-ene, but not when each carbon carries different substituents. For those cases E/Z is used: on each carbon of the double bond you pick the substituent with the higher CIP priority; if both are on the same side it is Z (zusammen, together) and if they are on opposite sides it is E (entgegen, opposite).

Cis and Z do not always match. In 1-bromo-2-chloropropene you cannot speak of cis or trans, because the second carbon has no hydrogen, but you can use E and Z: bromine and chlorine are the priority substituents on each side. Rings work in a similar way: in 1,2-dimethylcyclohexane the two methyl groups are on the same face of the ring (cis) or on opposite faces (trans), and each isomer corresponds to a specific combination of R and S.

The program applies the CIP rules for atomic number and duplicate atoms (multiple bonds and rings), which are enough for the molecules in an organic chemistry course. It does not consider isotopes or the rules that tell apart branches differing only in their own stereochemistry, such as pseudoasymmetric centers (r/s). The geometry comes from a simple spring model: angles and configurations are faithful, but it is not a quantum-chemical optimization.