Introduction

We just spent the last 2 chapters talking about substitution vs elimination reactions, and, while it was briefly mentioned, we didn’t go into full detail on when each of these reactions typically occurs. In this chapter, we’ll do just that studying substitution vs elimination. Soon, you’ll be able to look at the nucleophile/base and the substrate for a reaction and identify whether those reagents will favor an SN2 reaction, an SN1 reaction, an E2 reaction, or an E1 reaction. We even provide an easy-to-read flow chart for reliably solving substitution versus elimination problems.

This chapter is often tricky for Organic Chemistry students as the way many textbooks present the topic is confusing, even appearing contradictory at times. The goal of this chapter is to simplify this complex material by breaking it into 3, very manageable parts.

Typically, an Organic Chemistry professor will give their students the substrate and the nucleophile/base and ask about which mechanism (SN1 mechanism, SN2 mechanism, E1 mechanism, or E2 mechanism) will be favored and the resulting product. Although we have learned about substitution vs elimination reactions separately up to this point, we will now put them together and learn how to distinguish between the two.

 

Substitution vs Elimination

There are 3 factors that must be examined to decide whether a molecule goes through an substitution vs elimination:

  1. The leaving group
  2. The substrate (the molecule containing the leaving group that either the nucleophile attacks or the base deprotonates)
  3. The strength of the nucleophile/base

Below is a figure showing the leaving group, substrate, and nucleophile in a typical substitution reaction:

 

This figure shows the critical components used to decide if a reaction will go through substitution vs elimination.

 

The same language holds for elimination reactions, except a base is used instead of a nucleophile (see “Keep it Simple” below).

 

Keep it Simple
A common area of confusion for students is the difference between the terms “nucleophile” and “base.” A nucleophile is a molecule that attacks the substrate in a substitution reaction, while a base is a molecule that deprotonates the substrate in an elimination reaction. To add to the confusion, the same molecule can often act as a nucleophile or a base in different situations.

For example, -OH is both a strong nucleophile and a strong base. When the –OH is involved in elimination reactions, it is acting as a base; however, when it is involved in substitution reactions, it is acting as a nucleophile.

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Factor 1: The leaving group

The leaving group is the part of the substrate that leaves during the reaction. We ask ourselves a simple question when we assess the leaving group: “Is the leaving group stable enough to leave or not?”

There are many, many different leaving groups, but below is a list of the most common leaving groups.

 

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Example
Does the following molecule have a leaving group that can leave the molecule?

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Answer
Yes, chlorine can be a leaving group here.

Example
Can a substitution reaction occur in the following conditions?

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Answer
No because there is no good leaving group on the substrate.

By itself, the hydroxyl group cannot leave this molecule. However, we can make a hydroxyl group into a good leaving group with a small transformation (see below).

 

The –OH Leaving Group—A Special Case

On our figure of good and bad leaving groups, note that -OH is listed as a bad leaving group, while H2O is listed as a good leaving group.

Say that we had a molecule with an –OH, and we wanted it to leave. How could we accomplish this? What if we just turned the –OH in H2O? We can do this with the simple addition of acid.

Picture107
Just like that, we are able to turn a bad leaving group into a good leaving group. Keep this concept in mind through future chapters as it is a common reaction in organic chemistry.

 

Factor 2: The substrate

This one is easy. Find the location of the leaving group, and note whether it is located on a primary, secondary, or tertiary carbon on the substrate.

If the leaving group is primary, then the reaction will typically be either E2 or SN2. If the leaving group is secondary, the reaction will tend to be E2 or SN2. If the leaving group is tertiary, the reaction will tend to be E2, SN1, or E1.

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Factor 3: the strength of the nucleophile/base

We will classify our nucleophiles and bases as either strong nucleophile/ bases, weak nucleophiles/ bases, or an exception that fits outside the previous 2 categories. To do this, we analyze the stability of the molecule using the same acid/base principles presented in the Acid/Base Chapter. To quickly summarize how stability is related to reactivity:

 

Picture109

 

Factors that affect stability include the atom on which the charge is located, the presence of resonance structures, inductive forces present in the molecule, and the orbital of the atom. If you have trouble remembering these, review this section of the acids/bases section that talks about molecular stability.

 

As we just mentioned above, we’ve created 3 main categories of nucleophiles/bases.

  1. Strong nucleophiles/ strong bases: These molecules are fairly unstable, and as a result, they want to react more. Examples include anything with a negative charge on an oxygen atom.
  2. Weak nucleophiles/ weak bases: These molecules are much more stable and, as a result, more unreactive. These molecules are often uncharged, like H2O, for example.
  3. Exceptions: The molecules are exceptions to the categories above as they only react as either a base or nucleophile. Exception molecules that only act as a nucleophile will only undergo substitution reactions, while molecules that only act as a base will only undergo elimination reactions.

Below is a list of common molecules seen in organic chemistry, broken into their respective categories.

 

Picture110

 

 

 

 

So, Substitution vs Elimination (SN2, SN1, E2, or E1)?

The flow chart below gives an easy-to-understand method for reliably finding whether the reaction will be substitution versus elimination using the 3 factors discussed above. A few points to remember from previous chapters:

  • SN1 and E1 reactions are subject to carbocation rearrangements (from a hydride or methyl shift) due to the presence of an sp2-hybridized intermediate in the mechanism. SN2 and E2 don’t have a carbocation intermediate, so no rearrangement can occur.
  • Once you’ve determined an elimination reaction is going to take place, remember to assess the “bulkiness” of the base to see whether the Hoffman or Zaitsev product is formed.
  • Remember, SN2 reactions result in inversion of stereochemistry. SN1 reactions form racemic products (an equal mix of both enantiomers).

 

Full flow chart for determining substitution vs elimination.

 

 

Let’s do some substitution vs elimination practice problems.

 

Example
What is the major product of the reaction below? What is the reaction mechanism used? Show the mechanism.

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Answer
E2 reaction

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Factor 1. The Leaving Group: The leaving group here is bromine, which is stable enough on its own to be able to leave the molecule.
Factor 2. The Substrate: The leaving group is on a secondary carbon.
Factor 3. The Nucleophile/Base: -OH is a strong nucleophile/base.

Following the flow chart above, we see this will react via an E2 mechanism. Since –OH is a non-hindered base, the Zaitsev product will be formed.

Picture114

 

Example
What is the major product of the reaction below? What is the reaction mechanism used?

Picture115

Answer
SN1 reaction

Picture116

Factor 1. The Leaving Group: The leaving group here is bromine, which is stable enough on its own to be able to leave the molecule.
Factor 2. The Substrate: The leaving group is on a tertiary carbon.
Factor 3. The Nucleophile/Base: The sulfur atom containing the negative charge is an exception as it only reacts as a nucleophile.

Following the flow chart, we see this will react via an SN1 mechanism. This makes sense as sulfur only wants to be a nucleophile (which points towards substitution) and the leaving group is on a tertiary carbon (which points towards SN1 because of the stability of the carbocation).

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