By James Ashenhurst
Guest Post On SN1/SN2/E1/E2 (6): Wrapup
Last updated: March 29th, 2019
3 ½ Steps To Any SN1/SN2/E1/E2 Reaction: Wrap Up And Cautions, by @azmanam
Congratulations! You now have all the information you need to help Dr. House diagnose any reaction your professor throws at you. Let’s review what we’ve learned so far. 1) Electrons don’t like to be confined. The more electron density you have in a small volume, the more unstable the molecule will be. 2) The leaving group must be able to accept a pair of electrons and be stable when it leaves. The best leaving groups are weak bases. Beware, the leaving group must be located on an sp3-hybridized carbon atom. 3) Strong nucleophiles and strong bases have lots of electron density concentrated in a very small volume. 4) Electrophiles are classified based on two variables: steric hindrance of the electrophilic carbon atom, and ability to form a relatively stable carbocation. 5) Solvents can either diffuse electron density or concentrate electron density, and can be used as a tie-breaker if needed.
Each piece of the reaction provides us different evidence for or against certain mechanisms. Here is the chart we’ve been building over the last couple of posts.
|Classification||Evidence for||Evidence against|
|Strong nuc/strong base||SN2, E2||SN1, E1|
|Strong nuc/weak base||SN2||SN1, E1, E2|
|Weak nuc/strong base||E2||SN1, SN2, E1|
|Weak nuc/weak base||SN1, E1||SN2, E2|
|Methyl||SN2||SN1, E1, E2|
|Primary||SN2, E2||SN1, E1|
|Secondary||SN1, SN2, E1, E2|
|Tertiary||SN1, E1, E2||SN2|
|Polar protic||SN1, E1, E2||—|
Now it’s just a matter of assessing the evidence from each piece of the reaction and making the diagnosis.
There are two final questions that must be addressed before we leave. What if the leaving group is attached to a stereocenter? And what if the carbocation can rearrange? The answer to the first question depends on which mechanism we are invoking. For the SN2, because the nucleophile must specifically approach the electrophile from a trajectory 180° opposed to the leaving group, the stereocenter will be inverted. For the E2, the leaving group and the β-proton must be anti-coplanar (this can sometimes be best viewed in a Newman projection or chair structure), and will lead to a specific E or Z alkene depending on the other groups on the electrophile. For the SN1 and E1, the intermediate carbocation can be attacked from either face of trigonal plane and has free rotation about all single bonds, so we tend to form a mixture of stereoisomers in the SN1 reaction, and – due to steric reasons – typically the isomer with the large groups ‘trans’ in the E1.
What if the carbocation can rearrange? Well, only SN1 and E1 even form carbocations, so we only need to answer this question if we decide were using one of these mechanisms. Carbocations are inherently unstable, and carbocation will only rearrange if we can sacrifice an unstable carbocation to gain a more stable carbocation. Alkyl groups and resonance stabilize carbocations. So we will only rearrange a carbocation if we can increase the number of alkyl groups and/or stabilize the carbocation through resonance. Hydride (H–) and alkyl groups are the most common groups to migrate, if rearrangement can occur.
Want some examples? OK! Some of these are more straight forward, and some will force you to make decisions based on conflicting evidence!
So enjoy your newfound expertise with substitution/elimination mechanisms. Remember, if you bring everything back to electron density, it all starts to make sense.