Question

Rank the substituents in each of the following sets according to the CahnIngold-Prelog rules: (a) \(-\mathrm{H},-\mathrm{OH},-\mathrm{CH}_{2} \mathrm{CH}_{3},-\mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) (b) \(-\mathrm{CO}_{2} \mathrm{H},-\mathrm{CO}_{2} \mathrm{CH}_{3},-\mathrm{CH}_{2} \mathrm{OH},-\mathrm{OH}\) (c) \(-\mathrm{CN},-\mathrm{CH}_{2} \mathrm{NH}_{2},-\mathrm{CH}_{2} \mathrm{NHCH}_{3},-\mathrm{NH}_{2}\) (d) \(-\mathrm{SH},-\mathrm{CH}_{2} \mathrm{SCH}_{3},-\mathrm{CH}_{3},-\mathrm{SSCH}_{3}\)

Short answer

(a) -OH > -CH₂CH₂OH > -CH₂CH₃ > -H. (b) -CO₂H = -CO₂CH₃ > -CH₂OH > -OH. (c) -CN > -CH₂NHCH₃ > -CH₂NH₂ > -NH₂. (d) -SSCH₃ > -SH > -CH₂SCH₃ > -CH₃.

Step-by-step solution

Assign Priority by Atom Number (CIP Rule 1)

In the Cahn-Ingold-Prelog (CIP) priority system, start by comparing the atomic numbers of the atoms directly attached to the chiral center. Higher atomic numbers take precedence. This means a hydrogen (-H) has the lowest priority as its atomic number is 1, whereas oxygen has an atomic number of 8, and carbon 6.

Set (a) Evaluation

For Set (a): - Compare -H, -OH, -CH₂CH₃, -CH₂CH₂OH. - OH has oxygen directly attached (O = 8), - CH₂CH₂OH has carbon directly attached but the second carbon is directly bonded to an oxygen, - CH₂CH₃ has carbon directly attached, and - H is hydrogen (lowest). Therefore, priority is: -OH > -CH₂CH₂OH > -CH₂CH₃ > -H.

Set (b) Evaluation

For Set (b): - Compare CO₂H, CO₂CH₃, CH₂OH, OH. - CO₂H: oxygen has atomic number 8, - CO₂CH₃: oxygen, - CH₂OH: carbon bonded to oxygen, - OH directly has oxygen. Thus, priority: -CO₂H = -CO₂CH₃ > -CH₂OH > -OH.

Next Atom in the Chain(CIP Rule 2)

If direct atoms have the same rank, move to atoms connected directly to these primary atoms. Evaluate secondary criteria if necessary.

Set (c) Evaluation

For Set (c): - Compare -CN, -CH₂NH₂, -CH₂NHCH₃, -NH₂. - CN: carbon bonded to nitrogen (7 and 6), - CH₂NH₂: carbon bonded to nitrogen, - CH₂NHCH₃: carbon bonded to nitrogen and additionally methyl group, - NH₂: only nitrogen. Thus, priority: -CN > -CH₂NHCH₃ > -CH₂NH₂ > -NH₂.

Set (d) Evaluation

For Set (d): - Compare -SH, -CH₂SCH₃, -CH₃, -SSCH₃. - SH: sulfur (16) is higher, - CH₂SCH₃: carbon bonded to sulfur, - CH₃: only carbon, - SSCH₃ additionally sulfur and methyl group. Therefore, priority: -SSCH₃ > -SH > -CH₂SCH₃ > -CH₃.

Key concepts

Priority Assignment

In the Cahn-Ingold-Prelog (CIP) system, determining the order of substituents around a chiral center involves a key step referred to as priority assignment. Here is how it works:

• Start by identifying the chiral center in the molecule which is typically a carbon atom bonded to four different substituents.
• Focus on the atoms directly bonded to this chiral center.
• Assign priorities based on the atomic numbers of these directly attached atoms: the higher the atomic number, the higher the priority.

For example, oxygen (atomic number 8) would take precedence over carbon (atomic number 6). This technique helps systematically determine the spatial arrangement of substituents, which is a crucial part of stereochemistry.
If two substituents share the same element, further criteria look to their bonded atoms, but this process starts with a straightforward comparison based on atomic numbers.

Atomic Number Comparison

A fundamental principle in applying the CIP rules is comparing atomic numbers of atoms directly attached to the chiral center. This process begins by evaluating the mass and atomic number of each of these atoms:

• The atom with the highest atomic number receives the highest priority among the substituents.
• Continuity is kept as you go down the list of substituents, assigning priorities by decreasing atomic numbers.
• For example, in the case of substituents like -H, -OH, and -CH₃, oxygen (from -OH) receives higher priority than carbon (from -CH₃), and both, in turn, rank higher than hydrogen.

If the direct atoms have the same priority, the decision-making process moves one atom further along each substituent until a difference is found. This ensures that every substituent can be uniquely ranked.

Chiral Center

The concept of a chiral center is essential in understanding stereochemistry and appreciating how molecules can have different 3D shapes despite the same molecular formula. A chiral center, often a carbon atom, shifts focus to its four substituents, each being distinct from the others. Here are a few interesting points on chiral centers:

• By definition, a chiral center is asymmetric, meaning it lacks an internal mirror plane.
• The arrangement of substituents around a chiral center affects not just its priority assignment but also its chemical behavior and interactions.
• In molecules with multiple chiral centers, the complete 3D shape is determined by how each center's substituents are arranged—a process often made comprehensible using the CIP rules to differentiate between configurations such as R and S.

Understanding chiral centers is crucial for stereochemical analysis and is fundamental in fields like pharmaceuticals, where the shape and configuration of molecules can dramatically influence biological activity.