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

Having gone through the SN1, the SN2, the E1, and the E2 reactions 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 reactionsA wide variety of solvents can be used in substitution and elimination reactionsWe 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.

It starts by asking questions. In order of importance, I think they are:

The substrateThe nucleophile/baseThe solventThe temperature

It’s also a process of, 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.

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 > tertiaryThe “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?

If the substrate is?primary, we can rule out SN1 and E1, because primary carbocations are unstable. ?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).

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.

—————— Advanced readers only ————–

* 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.

Tagged as: e1, e2, elimination, sn1, SN2, substitution

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