Ch. 1 - A Review of General ChemistryWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch.2 - Alkanes and Cycloalkanes
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

By definition stereoisomers are molecules that share the same molecular formula but have different configuration in at least one stereocenter. They have the same atomic connectivity but a different arrangement in space. 

Stereochemical designations:

Cis and trans:

Due to the pi bond, alkenes don’t rotate under normal conditions so the arrangement of substituents is locked—this can create a stereogenic center. Disubstituted alkenes have two non-hydrogen substituents that can be distributed in three different ways as shown below:

Disubsituted alkenesDisubsituted alkenes

The molecules labeled cis and trans are stereoisomers (specifically diastereomers) of each other since they share the same atomic connectivity but different arrangement in space. The geminal alkene is a constitutional isomer of the other two because it has different atomic connectivity. 

What happens if the double bond is more than disubsituted? What happens if it’s trisubstituted or tetrasubstituted? These types of alkenes get their own naming convention that is more powerful than cis and trans, and we’ll talk about it in the diastereomers section below. 

R & S configurations

To be able to use R &S, we have to first be able to identify a chiral center. The most common chiral centers are carbon atoms connected to four unique substituents. In the molecules shown below, the central carbons have four unique substituents attached so they are considered chiral centers.  

Chiral-center-with-four-unique-groupsChiral center with four unique groups

The Cahn–Ingold–Prelog system is a great way to identify and name stereoisomers under IUPAC. It can differentiate between stereoisomers by assigning priorities to a chiral center’s substituents based on atomic mass. Priority 1 goes to the heaviest atom directly attached, and 4 goes to the lightest.

Depending on the arrangement of substituents, a chirality center can be either R or S. Tracing a clockwise circle around 1, 2, and 3 tells us it’s R; tracing a counter-clockwise circle tells us that it’s S. Let’s apply that to the above molecules: 

R and SR and S

Since both of our molecules have the lowest priority in the back, we don’t have to get fancy

Types of stereoisomers:

Enantiomers


EnantiomersEnantiomers

Since these two molecules have opposite R & S, they’re considered enantiomers. Notice that 100% of their chiral centers have opposite R & S configurations. Molecules with more than one chiral center can also have enantiomers like in the example below: 


Enantiomers with two chiral centers

Enantiomers with two chiral centers

Okay, cool. So, enantiomers are pairs of molecules in which all chiral centers change from R to S or vice-versa, but what are they called when not all the chiral centers change?

Diastereomers

Stereoisomers in which not all chiral centers change are called diastereomers. Let’s say there are two stereoisomers that have 100 chiral centers. Let’s say that 99 of them have the same R and S configurations but one is different. Those are still diastereomers because not all of the chiral centers are different. 

DiastereomersDiastereomers

Molecules with chiral centers aren’t the only diastereomers possible, though. Stereogenic centers like the disubstituted alkenes can be diastereomers as well if their spatial arrangement (cis/trans) is different. We assign priority values to alkene substituents by atomic weight just like in R & S configuration. 

Pent-2-enePent-2-ene

The molecules above show the exact same atomic connectivity, but they have different spatial arrangements. The one on the left is a cis alkene, and the one on the right is the trans version. What happens when there are more than two substituents? We assign priority to our substituents just like we did:

 3-chloropentene3-chloropentene

Notice that we prioritized our substituents in the exact same way, but we didn’t name the molecules cis or trans; instead we named them E and Z. E means that the highest-priority substituents are on the opposite side, and Z means they’re on the same side. Fun fact: E and Z are short for the German words Entgegen and Zusammen. 

Stereoisomers vs constitutional isomers:

Remember that stereoisomers have the same atomic connectivity but different spatial arrangement. That means that every time you spot molecules with the same chemical formula but different atomic connectivity, they're constitutional isomers. 

Stereoisomers vs constitutional isomersStereoisomers vs constitutional isomers

The molecules in row a) have the same atomic connectivity but different spatial arrangement, so they're stereoisomers. The molecules in row b) have the same chemical formula but different connectivity, so they're constitutional isomers. Row c) also has a pair of constitutional isomers. 



Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.