SN1/SN2/E1/E2 Decision

By James Ashenhurst

Identifying Where Substitution and Elimination Reactions Happen

Last updated: January 27th, 2023 |

Identifying Carbons Where Substitution and Elimination Reactions Can Take Place

summary-where will sn1 sn2 e1 e2 reactions occur - sp3 hybridized alkyl halides mostly

Table of Contents

  1. Look For A Good Leaving Group On The Substrate
  2. The Leaving Group Must Be On An sp3 Hybridized Carbon
  3. Identify The Type of Carbon As Primary, Secondary, or Tertiary
  4. Acid Makes Alcohols (and Ethers) Into Better Leaving Groups
  5. Multiple Functional Groups
  6. Epoxides
  7. Summary
  8. Notes
  9. Quiz Yourself!
  10. (Advanced) References and Further Reading

1. Look For A Good Leaving Group On The Substrate

This article presumes you are familiar with the SN1, SN2, E1, and E2 reactions. If you need a review on any of these reactions, please follow these links and then come back.

In nucleophilic substitution reactions, the substrate or electrophile (an electron-pair acceptor, e.g. an alkyl halide) undergoes attack by a nucleophile (the electron-pair donor).  A new carbon-nucleophile bond forms, and a carbon-leaving group bond breaks off from the substrate.

In elimination reactions, a base breaks a C-H bond on the substrate, and a new C-C pi bond forms, with the breaking of a carbon-leaving group bond from the substrate.

Both of these reactions require the loss of a leaving group from the substrate (i.e. the molecule which is accepting a lone pair from the nucleophile, or is being deprotonated by a base).

how leaving groups work in substitution and elimination reactions

If there’s no good leaving group on the substrate… then no substitution or elimination reaction can happen! It’s that simple.

Common examples of good leaving groups are species that can be weak bases once they accept a lone pair of electrons:

  • Halogens (Cl, Br, I, but not F, as the C-F bond is very strong)
  • Sulfonates [OTs or OMs]
  • Acyloxy groups (O-C(O)R)
  • Positively charged groups containing oxygen [OH2 (+),  OH(R)(+)], nitrogen [NR3(+)], or even sulfur [SR2(+)]

partial list of good groups in nucleophilic substitution reactions and elimination

(There is an excellent correlation  between low pKa and leaving group ability of the conjugate base. For more on this, see article: What Makes A Good Leaving Group?)

Examples of poor leaving groups include strong bases such as hydroxide (HO), alkoxides, amides (NH2)hydride (H) and carbanions (R). The fluoride ion (F) also tends to be a poor leaving group in substitution and elimination reactions since it forms extremely strong bonds to carbon. [Note 1] The cyano group (CN) is a weak base but does not tend to act as a leaving group in substitution or elimination reactions. [Note 2]

a partial list of poor leaving groups in nucleophilic substitution and elimination

So the first order of business in determining the product of any of these reactions is to identify the site(s) on the substrate where there is a good leaving group

In other words, look for groups that will be weak bases when they accept a lone pair of electrons.

Not all molecules are capable of substitution or elimination!

For example, hydrocarbons do not act as substrates in SN1/SN2 or elimination reactions because the leaving groups would have to be the extremely strong bases H(-) or alkyl anions (e.g. CH3(-) ).

hydrocarbons do not undergo substitution or elimination

Some hydrocarbons can act as nucleophiles in substitution and elimination reactions, but that’s different than being the substrate. (See post: Acetylides from Alkynes And Their Use In Substitution Reactions)

These exercises give you the challenge of identifying sites on a molecule where substitution or elimination can occur.

If you identify the leaving group, then you are identifying at least one of the bonds that will break. You are halfway there!

Click to Flip

Here’s another set of examples.

Click to Flip

As these quizzes should hopefully have driven home, you want to look for halogenssulfonates, or other species that will be weak bases once they depart from the substrate.

Some groups that are poor leaving groups can be made into better leaving groups through the addition of acids. More on that below.

2. The Good Leaving Group Should Be Attached To An sp3 Hybridized Carbon

In substitution and elimination reactions, the transition state generally involves the formation of partial positive charge at the carbon bearing the leaving group.

Carbocations are most stable when they are formed through the loss of a leaving group on an sp3-hybridized carbon. Removing a leaving group from an sp2 or sp-hybridized carbon is very difficult, since the greater s-character means the electrons are held closer to the nucleus. [See article: Carbocation Stability] [Note 3]

So another key to identifying where a nucleophilic substitution or elimination reaction will occur is to examine the carbon attached to the good leaving group

  • If the leaving group is attached to an sp3 hybridized carbon, then this is a good candidate for the site of the reaction.
  • If it is attached to an sp2 or sp hybridized carbon, then it is unlikely to undergo nucleophilic substitution or elimination.

In this exercise, identify the carbon atoms which are capable of undergoing substitution or elimination.

Click to Flip

Here is another set of examples.

Click to Flip

It’s important to know the few exceptions. [Note 4]  Elimination to give alkynes occurs on sp2 hybridized carbon using the extremely strong base NaNH2. [See article: Alkynes via Elimination Reactions].

3. Identify The Carbon Attached To The Leaving Group As Primary, Secondary or Tertiary

Once a plausible site for substitution or elimination has been found, the next step is to be able to classify that carbon as primary, secondary or tertiary.

Why is this important?  Because it will greatly help in determining whether a reaction proceeds via SN1, SN2, E1 or E2 pathway.

I have more to say on this in the subsequent article (See article: SN1/SN2/E1/E2 – The Substrate)

Click to Flip

Here is another quiz:

Click to Flip

And another:

[11-possible]

4. Alcohols And Ethers Can Participate In Substitution and Elimination Reactions If Acid Is Present

If you have made it this far, and have not covered alcohols or epoxides, then you are probably ready to proceed to the next article.

If you are covering the substitution and elimination reactions of alcohols and ethers, however, you’ll need to know another important twist.

Hydroxyl groups (OH) are poor leaving groups in substitution and elimination reactions. Unless strong acid is present, in which case they can be protonated to give their conjugate acids. (See article: The Conjugate Acid Is A Better Leaving Group)

How do you know if the alcohol or ether might be protonated? Look for strong acids such as HCl, HBr, HI, H2SO4 or TsOH.

when alcohols are treated with strong acid good leaving group OH2 is formed

The restriction that substitution and elimination reactions only happen on sp3 hybridized carbons still applies, however.

See if you can identify the carbons in each case which can undergo substitution or elimination reactions.

Click to Flip

As a side note, positively-charged sulfur, nitrogen and even phosphorus can also be good leaving groups. The leaving group in these cases are neutral amines (NR3) sulfides (SR2) or phosphines (PR3).

examples of positively charged leaving groups

5. Situations With Two Leaving Groups

There are times where you will be presented with cases where multiple good leaving groups are present, and your challenge will be to find the one site on the molecule where substitution or elimination is most likely to occur.

As we saw before, look for a good leaving group attached to an sp3 hybridized carbon.

Click to Flip

You might see other groups like OH, NH2, or SH in addition to the good leaving group. Those are likely nucleophiles that will react with the substrate via an intramolecular substitution reaction. (See article: Intramolecular SN2 Reactions)

6. Epoxides

Epoxides are a special case of ethers that will undergo substitution reactions without the addition of acid. That is due to the considerable ring strain of the three-membered ring (See article: Epoxide Ring-Opening With Base).

epoxides can undergo sub and elim reactions

7. Summary

In summary, the process for identifying where SN1/SN2/E1/E2 reactions happen looks like this.

  • Identify good leaving groups (such as halides, but also OTs and OMs, among others)
  • … that are attached to sp3 (alkyl) hybridized carbons.
  • Additionally, alcohols and ethers can undergo SN1/SN2/E1/E2 if strong acid is present.

The next step is to identify the carbon bearing the leaving group as primary, secondary, or tertiary. That will help to narrow down whether the reaction will participate in an SN1, SN2, E1 or E2 reaction. More on that in the next post.

Next Post: Deciding SN1/SN2/E1/E2 – The Substrate


Notes

Note 1 – The bond dissociation energy of fluorine in CH3F is about 109 kcal/mol, even larger than the C-H bond dissociation energy (104 kcal/mol).

Note 2 – Despite being a weak base (the pKa of HCN is 9.2) the cyanide ion does not act as a good leaving group in SN2 reactions. In fact, methyl cyanide, more commonly known as acetonitrile, is a commonly used polar aprotic solvent for SN2 reactions.

Note 3 – The E1 and SN1 reactions go through carbocations, whereas the SN2 reaction requires a partially-positive charged carbon in the transition state.

[F1]

There are two ways of describing why alkenyl carbocations are less stable than alkyl carbocations.

One way of looking at it is that alkenyl and alkynyl carbons form stronger bonds to alkyl carbons, and it is therefore much more difficult for leaving groups to just leave.

Remember how s-orbitals are held closer to the nucleus, which is why acetylide ions are more stable than alkyl anions? You can think of alkenyl and alkynl carbons as having a great effective electronegativity than alkyl carbons, which makes them “hold on” to electrons more tightly and making it more difficult for an electron pair to leave.

[F2]

Personally, a more satisfying explanation is that there are fewer adjacent orbitals available to donate via hyperconjugatio in alkenyl (and alkynyl) carbocations than are present in alkyl carbocations (sp2).

[F3]

This also explains why carbocations on bridgehead atoms are difficult to form.

Note 4 – exceptions to no sp2. Alkyne formtion. SNAr

[F4]

Note 5 – sn2 prime


Quiz Yourself!

[quiz – bridghead]

[quiz – sn2 prime]


(Advanced) References and Further Reading

[References]

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