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Deciding SN1/SN2/E1/E2: The Key Role Of The Alkyl Halide (“Substrate”)

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). They do not occur with alkenyl (sp2-hybridized) or alkynyl (sp-hybridized) halides
Whether an alkyl halide is primary, secondary, or tertiary has a tremendous impact on which reaction pathway the reaction  will follow. We have seen how the SN2 pathway is retarded by steric hindrance, and carbocation formation is favored by increasing substitution by carbon   (i.e. tertiary > secondary > primary).
 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?

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

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

The substrate
The nucleophile/base
The solvent
The temperature

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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.

Quick N’ Dirty 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:

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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?

For Primary Carbons, Rule Out The SN1 and E1

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).

For Tertiary Carbons, Rule Out The SN2

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. 

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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 bromide”) 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.

Struggling with SN1/SN2/E1/E2?  Our Org 1 Summary Sheets (PDF) contain a full-page flowchart on deciding SN1/SN2/E1/E2, as well as two more pages summarizing substitution and elimination reactions, in addition to many other Org 1 topics. 

Check them out now! 

 

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