Predicting the Products of an SN1/SN2/E1/E2 Competition

When I teach nucleophilic substitution and elimination reactions, I find that students typically have very little trouble drawing each mechanism and predicting the products, so long as they are specifically told which reaction. But many students find one aspect very challenging: predicting the winner of an SN1/SN2/E1/E2 competition. In my first few years of teaching, I dreaded giving and grading my second exam, the exam that covered this reaction competition. Many good students would receive a very low grade, thus creating poor class morale for the rest of the semester. The SN1/SN2/E1/E2-competition exam was the exam where many pre-health students decided that their fate was sealed. In the years since then I have turned things around considerably. What did I learn? And what did I change?

This most important thing I learned was why students were struggling with predicting which reaction dominates—students were memorizing! I initially thought it was strange that students were memorizing because I felt that the textbook I was using clearly explained the various factors that favor one reaction over another; and I heavily reinforced those ideas in class. But then it became apparent to me why students still resorted to memorization. After treating each of those factors separately, the textbook I was using brought them together to summarize and make generalizations about the competition, as well as to provide exceptions. For example, if (1) the attacking species is both a strong nucleophile and a strong base, and (2) the substrate is primary, then SN2 will give the major product and E2 will give the minor product. An exception is when the attacking species is the tert-butoxide anion, in which case E2 will give the major product and SN2 will give the minor. As another example, if (1) the attacking species is a strong nucleophile but a weak base, and (2) the substrate is secondary, then both SN1 and SN2 can occur. In an aprotic solvent, however, we can expect SN2 to dominate.  But if the substrate is benzylic, the solvent is protic, and the leaving group is very good, then we can expect SN1 to dominate.

Not surprisingly, when a student sees that 15 pages of chemistry has been distilled down to a single page (or a single table) of summary/generalizations, it is incredibly attractive to try to memorize them. There are two major problems that arise. One is that, by doing so, students circumvent the actual chemistry, so there ends up being no context for why a particular reaction dominates. This makes it easy for a student to forget a critical piece of information or become confused, especially given the large number of different combinations in which the factors can contribute. The second problem is that, in addition to memorizing the general rules, students must also remember which scenarios require additional information, such as when to consider solvent, the bulkiness of the attacking species, or the benzylic nature of the substrate. In other words, students feel that they must memorize exceptions in addition to the rules.

I’ve since had a huge effect on my students’ success with the SN1/SN2/E1/E2 competition by providing a system for deciding the winner of the competition, which consists of the following steps:

(1)  Determine if the leaving group on the substrate is at least as good as F. If so, then

(2)  Examine the type of carbon to which the leaving group is attached.

  1. If the carbon is primary, then rule out SN1 and E1 unless the carbocation can be resonance-stabilized.
  2. If the carbon is tertiary, then rule out SN2.

(3)  Construct the following table, and for each factor, add a check mark to the column for the reaction that is favored.

Factor SN1 SN2 E1 E2
Strength of attacking species
Concentration of attacking species
Type of carbon atom
Type of Solvent

(4)  The column with the most check marks is the winner.

(5)  If there is a tie between substitution and elimination, heat favors elimination.

This system is also incorporated into my new textbook for two reasons. First, it gives students something to hang their hat on. Yes, students must still remember how to execute these steps, but the system for doing so does not change from one scenario to the next. The second great benefit is that when going through these steps, students will frequently be reminded why. When deciding whether a leaving group is at least as good as F, for example, they must apply arguments of charge stability. When the carbon is tertiary, which rules out SN2, students will be reminded that it is due to steric hindrance. And it is this type of reinforcement that sets students up for being in command of other reactions they will encounter in the course.

— Joel Karty

5 comments on “Predicting the Products of an SN1/SN2/E1/E2 Competition

  1. Marie Melzer
    June 18, 2013 at 3:44 pm #

    I used this methodology for the first time this summer (along with the elementary steps mechanism approach, Chapter 7) and saw 20 point increase in the exam average.

    Thank you!!!

  2. Jules G.
    March 26, 2014 at 9:36 pm #

    Hi. I am an Orgo I student and am very interested in this approach because I am becoming overwhelmed with what to memorize and what not to. Can you please clarify a few things?
    1. What do you mean by a leaving group “as good as F-“? What about OH- leaving group?
    2. What do you mean by the “concentration of the attacking species”?
    3. Also, doesn’t it matter if the attacking species is a good Nu or a good base? Or both? I know that something that is just a good base will only favor certain reactions. I’m still a little confused by which ones are good Nu’s, bases or both and if those are things I should just memorize…
    Thanks for any help. I am glad I discovered this site!
    Jules

  3. Joel Karty
    April 2, 2014 at 2:30 pm #

    Hi Jules.

    Thanks for your post. Let me see if I can answer your questions….

    1. A leaving group “as good as F-” essentially has to do with charge stability of the leaving group in the form in which it comes off. Cl-, for example, is a much better leaving group than F- because, being a larger atom, chlorine can better handle the charge. H2O is also a much better leaving group than F- because it is uncharged. HO- is a worse leaving group than F- because O is not as electronegative as F, meaning that the negative charge cannot be accommodated as well. There is also a nice correlation between how good a leaving group is and the pKa of its conjugate acid: The stronger the conjugate acid, the better the leaving group is. The pKa of HF, for example, is around 3 and the pKa of HCl is around -7. HCl is a much stronger acid than HF, so Cl- is a better leaving group than F-.

    2. The attacking species is the species that can act either as a nucleophile or as a base. In short, the higher the concentration of the attacking species, the more that SN2 and E2 reactions are favored in the competition, whereas the lower the concentration of the attacking species, the more that SN1 and E1 reactions are favored. This can be understood from the rate laws of the respective reactions, but I like to add a more qualitative argument to the picture, which goes something like this: In an SN2 or E2 reaction, the attacking species is responsible for “forcing off” the leaving group (either directly or indirectly). Therefore, the greater the number of attacking species, the better that job can be accomplished. In an SN1 or E1 reaction, on the other hand, the attacking species must wait for the leaving group to have come off. Therefore, increasing the number of attacking species just means that there are more of them waiting.

    3. I think this question relates very closely to the qualitative picture in #2 above. Strong nucleophiles favor SN2 over SN1 because they are good at forcing off the leaving group. Strong bases favor E2 over E1 for the same reason. An attacking species like HO-, for example, is a strong nucleophile and a strong base, so it tends to favor both SN2 and E2 over SN1 and E1. Cl-, on the other hand, is a strong nucleophile but a weak base, so it tends to favor SN2 over SN1 (strong nucleophile), but favors E1 over E2 (weak base). Now, identifying an attacking species as a strong base or strong nucleophile is important. There’s a bit more to it than this, but basically, strong nucleophiles tend to have a full negative charge, and strong bases are ones that are roughly as strong as HO- or stronger.

    Let me close by saying that working through an SN1/SN2/E1/E2 competition should primarily involve applying fundamental concepts, not memorizing. If you find that you are spending a lot of time and effort trying to memorize things, you need to know that there is a much better way.

    • jules
      April 2, 2014 at 5:44 pm #

      Thanks so much for your help. I will try to nail these concepts down!

  4. orgchemby
    August 16, 2014 at 6:34 am #

    Your approach was mentioned in the lattest JCE issue (dx.doi.org/10.1021/ed400908g), and I find it more useful than the Labyrinth by Kate Graham.

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