Deciding SN1/SN2/E1/E2 (1) – The Substrate

by James

in Organic Chemistry 1, Organic Reactions

Having gone through the SN1, the SN2, the E1, and the E2 reactions in turn, we can now say the following:

  • Both substitution reactions and elimination reactions occur with alkyl halides (and related species)
  •  A wide variety of nucleophiles/bases can be used to perform substitution and elimination reactions
  • A wide variety of solvents can be used in substitution and elimination reactions
  • We also have to gauge the importance of factors such as the leaving group and temperature.

This is a lot of different factors to think about. Let’s look at some examples of situations you might encounter:

This is often one of the most difficult parts of organic chemistry for new students: how to weigh multiple (and often contradictory) factors? How do we know which factor is most important? Do we pay attention to the base, substrate, temperature, solvent? How do we go about sorting through a problem like this? As I’ve written before, deciding SN1/SN2/E1/E2 is not completely unlike how a professional bettor might evaluate which sports team is going to win on a given night (does good defence beat good offence? how important is coaching? how important is their recent performance? ) .

In this post and the next few, we’ll walk through one way of thinking about how to evaluate whether a reaction will proceed through SN1/SN2/E1/E2. It’s not 100% foolproof*, but it’s a decent enough framework for our purposes. Think of it as a set of 80/20 guidelines.  I call it this:

The Quick N’ Dirty Guide To Determining SN1/SN2/E1/E2, Part 1

It starts by asking questions. In order of importance, I think they are:
  1. The substrate
  2. The nucleophile/base
  3. The solvent
  4. The temperature

It’s also an approach where I tend to (at least in the beginning) ruling things out rather than ruling things “in”. In other words, seek to decide what options are not possible, rather than decide which are possible. It’s a subtle distinction, but a valuable one. Once you’ve crossed certain reactions off the list, you can then start asking yourself which reactions would be most consistent with the reaction conditions.

Remember: this is theQuick N’ Dirty” guide!  There will be some exceptions! (more on those at the bottom)

Before getting specific with each of those 4 questions, let’s start with the most important question you can ask in any situation like the ones above.

The most important step in evaluating any reaction is first to ask yourself “what type of functional group(s) are present in this molecule? This is because the type of functional group will dictate the type of reaction(s) that can occur. Note that in the questions above, all of the starting materials are alkyl halides or alcohols. Substitution/elimination reactions are possible for these substrates; many other reaction types (addition, for example) are not.

Question 1: The Substrate

Given that we’re looking at alkyl halides/alcohols, it’s a reasonable expectation that we should evaluate SN1/SN2/E1/E2. The next step is to identify the type of alkyl halide we are dealing with.
Look at the carbon that contains the best leaving group. Typically this is Cl, Br, I or some other group that can act as a good leaving group.
Ask yourself: is this carbon primary, secondary, or tertiary?

Given what we know about SN1, SN2, E1, and E2 reactions, we can say the following:

  • The “big barrier” to the SN2 reaction is steric hindrance. The rate of SN2 reactions goes primary > secondary > tertiary
  • The “big barrier” to the SN1 and E1 reactions is carbocation stability. The rate of SN1 and E1 reactions proceeds in the order tertiary > secondary > primary.
  • The E2 reaction has no “big barrier”, per se (although later we will have to worry about the stereochemistry)

So how can we apply what we know about each of these reactions to simplify our decision?

Quick N’ Dirty Rule #1: If the substrate is primary, we can rule out SN1 and E1, because primary carbocations are unstable* (see below for exceptions).  You cannot definitively rule out E2 yet, although I will spill the beans and say that it’s almost certainly going to be SN2 unless you are using a very sterically hindered (“bulky”) base such as tert-butoxide ion (e.g. potassium t-butoxide KOtBu).

Quick N’ Dirty Rule #2: If the substrate is tertiary, we can rule out SN2, because tertiary carbons are very sterically hindered.

If the substrate is secondary, we can’t rule out anything (yet).

As you can see, based on the information we’ve evaluated so far, we can’t make a definitive decision on SN1/SN2/E1/E2. We’ll have to look at some other factors before we can make a final decision. Next, we’ll evaluate the role of the nucleophile/base.

Next Post: The Role of The Nucleophile

—————-END OF QUICK N’ DIRTY GUIDE, PART 1 ————————–

NOTES: One final word of warning on the substrate: SN1/SN2/E1/E2 reactions tend not to occur on alkenyl or alkynyl halides. So if you see one of the substrates below, it is highly likely that no reaction will occur. 

Why are alkenyl and alkynyl halides so bad? Well, the SN1, SN2, and E1 mechanisms all involve considerable build-up of positive charge on the carbon bearing the leaving group, and the stability of sp2 and sp hybridized carbocations is much lower than that for sp3 hybridized carbocations [for the same reason that sp and sp2 anions are more stable than sp3 carbanions!].

E2 reactions are also more difficult due to the stronger C-H bonds of alkenes. [We'll see later that there is one example of an E2 that can occur on alkenyl halides, but the point remains that they are very rare!]

—————— EXCEPTIONS ————–

* One question that comes up a lot is this: are there exceptions? Keeping in mind the two themes of “steric hindrance” and “carbocation stability”, there are edge cases where we can have a particularly sterically hindered primary alkyl halide, or a particularly stable primary carbocation.

For instance, the alkyl halide below (“neopentyl chloride”) is indeed primary, but is so crowded on the carbon adjacent to the primary alkyl halide that it is essentially inert in SN2 reactions. On the SN1/E1 side, the allyl halide below, while primary, can undergo SN1/E1 reactions because the resulting carbocation is stabilized through resonance. As long as you keep in mind the “big barriers” for each reaction, you should be fine.

 

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{ 7 comments… read them below or add one }

ranjitha January 29, 2013 at 10:30 am

what are the products formed in the above given reactions?

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ranjitha January 29, 2013 at 10:39 am

sorry! i got the answer after going through part 2,3,4..

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ashley October 28, 2013 at 9:27 pm

How can you tell when a compound is stabilized by resonance, and it only important in Sn1 or E1 reaction mechanisms and not the other two?

Reply

Nik November 4, 2013 at 1:30 pm

The compound is stabilized by resonance if the formation of resonance structures is possible on the carbocation. This only matters in SN1 and E1 because those are the only two reactions where carbocations are formed. For example look at the isoprenyl bromide he has drawn above. If you remove the Br leaving group you’re left with a positive charge on the carbon it was previously attached to. If you move the double bond over to the right, making a resonance structure, the positive charge is now on a tertiary carbon, making it a more stable carbocation. If the reaction is SN2 or E2 don’t worry about resonance because its all happening in one step and no carbocation is formed.

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Lisa March 31, 2014 at 2:27 pm

So for the exception, primary carbocations are possible if they are allylic or benzylic…cuz resonance?

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James April 15, 2014 at 10:40 am

Yes!

Reply

VMath May 1, 2014 at 1:36 pm

In the example of bromopropane, why can we not consider carbocation rearrangement?

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