Deciding SN1/SN2/E1/E2 (2) The Nucleophile/Base

by JAMES
in ALKYL HALIDES, ORGANIC CHEMISTRY 1

Last time I talked about the process of deciding if a reaction goes through
SN1, SN2, E1, or E2 as asking a series of questions. I call it The Quick
N Dirty Guide To SN1/SN2/E1/E2. This is the second instalment.
Once weve looked at a reaction and recognized that it has
the potential for proceeding through SN1/SN2/E1/E2 that is, is it an
alkyl halide, alkyl sulfonate (abbreviated as OTs or OMs) or alcohol
and asked whether the carbon attached to the leaving group is primary,
secondary, or tertiary, we next can look at the reagent for the reaction.
In substitution reactions, a nucleophile forms a new bond to carbon, and
a bond between the carbon and the leaving group is broken. In
elimination reactions, a base forms a new bond with a proton from the
carbon, the C-H bond breaks, a C-C bond forms, and a bond between
carbon and leaving group is broken.
Theres a lot of confusion from students on this point. How do I know
whats a nucleophile and whats a base?.

Whether something is a nucleophile or a base depends on the type of

bond it is forming in the reaction. Take a species like NaOH. Its both a
strong base and a good nucleophile. When its forming a bond to
hydrogen (in an elimination reaction, for instance), we say its acting as a
base. Similarly, when its forming a bond to carbon (as in a substitution
reaction) we say its acting as a nucleophile.
In other words, its a relationship. For instance, when Im interacting with
my wife, Im interacting with her as a husband. When Im talking to my
mom, Im interacting with her as a son. Im the same person, but
depending on whom Im interacting with, our relationship has different
names.
Anyway. All this is prelude to making the key determination for today,
which is:

1. Charged bases/nucleophiles will tend to perform SN2/E2 reactions.

2. Reactions where neutral bases/nucleophiles are involved tend to go
through carbocations (i.e. they tend to be SN1/E1).
Again: Quick N Dirty is an 80/20 set of principles. There are
exceptions!!! But this framework will help us in most situations.
Charged Nucleophiles/Bases
Lets talk about charged nucleophiles first. Its important to be able to
recognize charged nucleophiles. The charges are often not written in, but
implied. For example, NaOEt (sodium ethoxide) actually has an ionic
bond between Na(+) and (-)OEt, even though the charges themselves
arent written in (us chemists are lazy that way). So if you see Na, K, or Li,
for instance, youre looking at a charged nucleophile/base. Whether its
K, Na, or Li doesnt matter for our purposes these are just spectator
ions.

In both the SN2 and E2 pathways the reaction is concerted that is, the
nucleophile/base forms a bond as the C-LG bond is broken. Since there
is significant bond-breaking occurring in the transition state, the energy
barrier for this step is higher than in the case of the E1 or SN1; were
going to require a stronger nucleophile/base to perform these reactions.
Recall that the conjugate base is always a stronger nucleophile. Negatively
charged species have a higher electron density and are more reactive than
their neutral counterparts.
Quick N Dirty Rule #3: If you see a charged nucleophile/base, you can
rule out carbocation formation (i.e. rule out SN1/E1). In other words, the
reaction will be SN2/E2.
We can break things down even more, depending on how strong a base
the charged species is; go to the section at the bottom of this post for
some examples where we can use base strength to rule out E2.

Reactions of Neutral Bases/Nucleophiles

Neutral bases/nucleophiles tend to be weaker than negatively charged
bases/nucleophiles. In order for them to participate in substitution or
elimination reactions, generally the leaving group must depart first, giving
a carbocation.

Quick N Dirty Rule #4: If you dont see a charged species present, youre
likely looking at a reaction that will go through a carbocation (i.e. an SN1
or E1).
One special case worth noting is if you see a strong acid such as H2SO4
or HCl with an alcohol as a substrate. Unless youre looking at a primary
alcohol (where carbocations are very unstable) the reactions in these cases
will almost always proceed through carbocations.

Its not uncommon to see a neutral nucleophile in the presence of a

charged one (see example 2, below). In that case its likely acting as
the solvent. Well talk about solvents next.
Heres a chart where we evaluate this second question for deciding if a
reaction is SN1, SN2, E1, or E2 (below).
Whats the biggest weakness of the Quick N Dirty approach? Its an
oversimplification. To conclude that a reaction proceeds SN2 or
proceeds E2 might give the impression that it gives 100% SN2 or 100%
E2, and that is surely not the case! Often, these reactions compete with
each other, and can therefore give mixtures products. When I say SN2 ,
for instance, I mean mostly SN2. There are likely other products in
there.
The key lesson here is to understand the concepts what conditions
favor each reaction? and then to be able to apply the rules you know
about each reaction to draw the proper product.
Next Post: The Role of Solvent
END QUICK N DIRTY GUIDE TO SN1/SN2/E1/E2 PART 2

Elaboration: Good Nucleophiles That Are Weak Bases

Some charged nucleophiles are actually poor bases. Heres a good rule of
thumb: if the conjugate acid of the base/nucleophile is less than 12, an E2
reaction will be extremely unlikely. So if you see a nucleophile like NaCl,
NaBr, KCN, and so on, it will favor SN2 over E2.
In contrast, the bulky base below (tert-butoxide ion) is a strong base but a
poor nucleophile due to its great steric hindrance, so an E2 reaction is
much more likely than SN2.

Exception: Neutral Nucleophiles in SN2 and E2 Reactions

One class of neutral nucleophiles/bases that readily perform E2 reactions
(and SN2) are amines. For example, the tertiary alkyl halide below will
undergo elimination through E2 here, although the Quick N Dirty rules
call for SN1/E1. Amines are generally not the most useful nucleophiles
for doing SN2 however because they lead to over-alkylation and
ammonium salt formation. Finally, there are also neutral species which
are good nucleophiles (and poor bases) such as PPh3, below.

Exception: Charged Nucleophiles In SN1 Reactions

Its also possible to use charged nucleophiles in SN1 reactions under
certain conditions. If you have, for instance a tertiary alkyl halide in the
presence of a high concentration of a good nucleophile (but weak base)
such as those above, the carbocation that forms can be intercepted by that
nucleophile. For example:

Here, the good nucleophile (cyanide ion), if present in large excess, can
overpower the weak nucleophile (solvent). Of course the ultimate artiber
of such statements are actual experiments.
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