🎯 Big picture
E2 reactions are a type of elimination reaction in which a base removes a β-hydrogen at the same time that the leaving group departs. Both events occur simultaneously in a single, concerted step.
The result is the formation of a double bond between the α- and β-carbons.
But when there’s more than one possible site for elimination, how do we know which alkene will form as the major product?
That’s where the classic Zaitsev vs. Hofmann question comes in.
Let’s walk through how to figure it out.
Step 1: Identify a good leaving group
First things first: check if your molecule has a good leaving group, one that can depart easily and stabilize the resulting negative charge.
Common examples include:
- Halides: Cl, Br, I
- Sulfonate esters: OTs (tosylate), OMs (mesylate), OTf (triflate)
If the leaving group is poor (like OH or NH2), elimination won’t proceed efficiently. However, poor leaving groups can be converted into good ones. For example, an alcohol (OH) can be converted into a tosylate (OTs), which is an excellent leaving group and far more suited for E2 reactions.
The carbon bonded to the leaving group is called the α-carbon, and it plays a central role in the reaction.
Step 2: Locate the β-hydrogens
Once you’ve identified the α-carbon, look at all carbons directly attached to it. These are the β-carbons.
For an E2 reaction to occur at a given β-carbon, it must have at least one β-hydrogen available for the base to abstract.
The double bond will form between the α-carbon and one of these β-carbons.
If a β-carbon doesn’t have any hydrogens, no elimination can occur from that position.
Step 3: Understand Zaitsev vs Hofmann products
When multiple β-carbons are available, elimination can lead to regioisomers. These are alkenes that differ in the position of the double bond.
You’ll usually see two possible products:
- Zaitsev product: the more substituted alkene
- Hofmann product: the less substituted alkene
So, which one dominates? It depends on the base.
Step 4: Analyze the base to determine the major product
If the base is small and unhindered, such as methoxide (MeO-), ethoxide (EtO-), or hydroxide (OH-), it can easily access the more substituted β-hydrogens.
That leads to the formation of the more stable, more substituted Zaitsev product.
On the other hand, if the base is bulky, such as tert-butoxide (tBuO-), lithium diisopropylamide (LDA), or DBN, it has trouble reaching crowded areas.
Steric hindrance limits its access, so it tends to pull a proton from the less substituted, more accessible β-carbon.
In that case, the Hofmann product becomes the major one, even though it’s less substituted and less thermodynamically stable
To predict the major product, analyze the base being used:
- Small base? Expect Zaitsev.
- Bulky base? Expect Hofmann.
Quick recap
1️⃣ Identify a good leaving group
2️⃣ Locate the β-hydrogens
3️⃣ Understand Zaitsev vs Hofmann products
4️⃣ Analyze the base to determine the major products
By following these steps, you’ll be able to confidently predict the major product of any E2 reaction. Keep practicing, and soon it will become second nature. 🚀
