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 we’ve 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 π bond forms, and a bond between carbon and leaving group is broken.

There’s a lot of confusion from students on this point. “How do I know what’s a nucleophile and what’s 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. It’s both a strong base and a good nucleophile. When it’s forming a bond to hydrogen (in an elimination reaction, for instance), we say it’s acting as a base. Similarly, when it’s forming a bond to carbon (as in a substitution reaction) we say it’s acting as a nucleophile. 

In other words, it’s a relationship. For instance, when I’m interacting with my wife, I’m interacting with her as a husband. When I’m talking to my mom, I’m interacting with her as a son. I’m the same person, but depending on whom I’m 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

Let’s talk about charged nucleophiles first. It’s 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 aren’t written in (us chemists are lazy that way). So if you see Na, K, or Li, for instance, you’re looking at a charged nucleophile/base. Whether it’s K, Na, or Li doesn’t 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; we’re 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 don’t see a charged species present, you’re 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 you’re looking at a primary alcohol (where carbocations are very unstable) the reactions in these cases will almost always proceed through carbocations.

It’s not uncommon to see a neutral nucleophile in the presence of a charged one (see example 2, below). In that case it’s likely acting as the solvent. We’ll talk about solvents next. 

Here’s a chart where we evaluate this second question for deciding if a reaction is SN1, SN2, E1, or E2 (below).

What’s the biggest weakness of the Quick N’ Dirty approach? It’s 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. Here’s 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.

5-naotbu

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

It’s 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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{ 21 comments… read them below or add one }

Ilmu Kimia December 4, 2012 at 1:33 am

If the alkyl halides are primary, they’ll react at SN2 with moderate base, like -OH, -CN, or CH3O-.
Thank’s for share.

Reply

Lee April 16, 2013 at 1:33 pm

Hi, what if you have a strong nucleophile and a strong base like OH- and you are reacting with a tertiary haloalkane. Does not Sn1 and E2 pathway is both possible? How would you then choose whether Sn1 work? Assume there is no solvent. Thanks!

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Akash May 11, 2013 at 9:02 am

E2 takes place as Oh- is a good nucleophile ie unstable so whatever comes into its hand it will take it moreover in Sn1 it needs to penetrate the steric hindrances provided therefore E2 is preferred.E2 doesnt need a polar aprotic solvent(we just say like that)

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Akash May 9, 2013 at 12:28 pm

CH3OH is acidic than water and for that matter any alcohol ROH is in equilibrium with RO- and H+,so wont RO- attack as a good nucleophile ?I know it is a weird question yet still how do we explain it will only ROH attacking always and not RO-.Pls reply ASAP

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james May 9, 2013 at 11:47 pm

Equilibrium for self ionization of alcohol ROH to RO- and H+ is disfavored by 10 to the 16th power.

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Akash May 11, 2013 at 12:36 am

but when we take reactions and see like weak base and weak acid,there is a formation of salt always.My point is if it starts the reaction then equilibrium shifts and whole of it would react!

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Akash May 11, 2013 at 11:36 am

in the exception column PPh3 undergoes SN2 but P is stabilized by 3 Ph and therefore will undergo Sn1 right?or is e- density on P high as it is not electronegative(unlike F) even after resonance stabilization?

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Akash May 11, 2013 at 11:38 am

regarding NR3,it is nucleophilic & is comparable with OH- due to the reason its lower electronegativity and inductive effect?

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Dave June 25, 2013 at 2:03 am

In Q2, part 3, Why is H2SO4 a neutral nucleophile? It seems like it would donate H+, and then become charged. HSO4- which is inert as a base (since it’s the conjugate base of a strong acid), but due to its negative charge could be a decent nucleophile.

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James Ashenhurst November 19, 2013 at 4:39 pm

The negative charge on oxygen in HSO4- is very resonance stabilized and simply does not act as a competent nucleophile in the vast majority of situations, so it’s easier to treat it as a non-nucleophile.

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Mohan Thomas November 8, 2013 at 12:19 pm

CH3OH is more acidic than water. The +I effect of CH3 group decreases the polarity of
O-H bond. What makes CH3OH more acidic.?

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emily November 18, 2013 at 11:10 am

Underneath where you wrote, “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.”

I think you have the wrong picture

thanks for this extremely helpful website though!

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Emmy November 19, 2013 at 2:44 pm

So, on my chemistry homework I have the following equation:

CH3CH2CH3CH3OCH3 + N3- ——–> ?

with a solvent of acetone.

Is this an SN1, SN2, E1, or E2 reaction? I think it might be an elimination 2 reaction but I am confused because in this case we are not removing a halite and N3- isn’t anything I have listed for a base/nucleophile in my notes.

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James Ashenhurst November 19, 2013 at 4:36 pm

Do you see a good leaving group…………? that’s always the first question to ask

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devesh December 29, 2013 at 9:47 am

Hey.Great site-I can understand and enjoy organic chem better now.
A Question.How can triphenyl phosphine be a good nucleophile ?? It has three phenyl rings then it should be sterically hindered.

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James January 9, 2014 at 8:27 pm

First of all the PPh3 has a trigonal pyramidal geometry, so a lone pair is pointing in the opposite direction from the phenyl groups. Secondly, the C-P bonds are fairly long which decreases the steric hindrance somewhat. PPh3 is a good enough nucleophile to do SN2 reactions of primary and secondary alkyl halides.

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Dorian March 9, 2014 at 8:28 pm

“Here’s a good rule of thumb: if the conjugate acid of the base/nucleophile is less than 12, an E2 reaction will be extremely unlikely.”

Less than 12 what? I’m confused here! This tip sound very handy but I have no idea why figure 12 is supposed to stand for!

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Fahim May 7, 2014 at 7:29 pm

I don’t know if you have figured it out already, but I still just wanted to quickly respond… the figure ’12’ as given in the situation you mentioned is the numerical value for the pKa of a given compound. Basically, it tells you via a numerical measure the extent of the acidity and/or basicity of a chemical compound you are looking at. So, as James says, “if the conjugate acid of the base/nucleophile is less than 12,” then the base is probably too acidic and not enough basic to act as an eliminating agent for the E2 reaction pathway to occur for that set of reactants and reagents.

You should to able to find good reference tables with pKa values calculated and already listed for organic compounds and the like, either online or in a major chemistry textbook (especially o-chem textbooks), if you need to look up values! Hope this helps!

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Dilek Sen April 2, 2014 at 4:18 pm

What do you mean by “the conjugate base is always a stronger nucleophile?”

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Sania September 8, 2014 at 11:49 am

Dilek, when we talk about CH3COOH It’s ionize form Is CH3COO- And H , inwhich CH3COO- is a conjugated base and a good nucleophile bcoz it is higly negative and can donate electrones more efficiently..

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Ojaswi Sinha October 14, 2014 at 7:22 am

Why comments are not seen??

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