S_N1 vs S_N2. Is it S_N1, S_N2, E1, E2?

This is such a common question, not only for students but on exams too.  How do you tell if it is S_N1 vs. S_N2? How the heck do you tell the difference between an E1, E2, SN1, SN2 reaction?  Check out the chart below to start.

The factors that will decide S_N1 vs S_N2 and whether it is S_N1, S_N2, E1, E2:

1) Do you have a strong nucleophile?  If you do, it will favor an S_N2 reaction in the S_N1 vs S_N2 fight.  If it is a mediocre nucleophile, it will favor an S_N1 reaction.  This is because of the two mechanisms.  In the S_N1, we have an open position (carbocation), so any old nucleophile can just waltz in and form a bond.  In the S_N2, we are pushing off the leaving group, which requires a stronger nucleophile.  What is a strong nucleophile?  Check out these blog posts on strong nucleophiles and strong electrophiles.

2) Does your nucleophile double as a base? If yes, it is going to favor elimination (E1/E2) over substitution (S_N1/S_N2).  Bases want to take protons, which leads to elimination.

3) How good is your leaving group?  If it is awesome, it is more likely to be a carbocation intermediate, ie E1 or S_N1 reaction.  If the leaving group is only OK, that means it has to be forced off and is more likely to be a concerted reaction mechanism like S_N2 or E2.

4) What is your solvent? Polar protic solvents will stabilize a carbocation better, therefore promote an E1 or S_N1 reaction.  Polar aprotic solvents favor S_N2 and E2.  This is because a protic solvent is more likely to stabilize a carbocation intermediate and therefore promote the E1/SN1 pathway.

5) What kind of substrate do you have?  If your starting material is a tertiary substrate, you are definitely E1 or S_N1.  If it is a primary substrate,  you are definitely S_N2 or E2. If it is a secondary substrate, it could go any one of the ways.

The S_N1 vs. S_N2 video:

Here are two videos were are particularly fond of that coach you through the way to decide which of these things it is.

Some Examples:

This is an easier example, but let’s start with it.  Here is the most important thing to see: The product has OTf substituted, NOT eliminated.  Just by looking at the product, we know it has to be an S_N1 or S_N2 reaction NOT an E1 or E2 reaction.  Therefore, when we look at the different factors below, we are going to ignore E1 and E2.

• Nucleophile: Cl is good but not great. Mediocre Nu = S_N1.
• Basic: NaCl is not basic.  No base = S_N1/S_N2.
• Leaving group: OTf is a dynamite leaving group.  Awesome LG = S_N1.
• Solvent: tBuOH is a polar protic solvent = S_N1.
• Substrate: It’s tertiary at the leaving group = S_N1

All of the factors point to an S_N1 reaction, therefore I feel comfortable saying it is an SN1 reaction.

How about this one:

This is still clearly a substitution, but it’s on a secondary substrate, so it could go either S_N1 or S_N2.  Here are the factors:

• Nucleophile: CN is a great nucleophile.  Great Nu = S_N2
• Basic: NaCN is not basic.  No base = S_N1/S_N2, but we already knew that.
• Leaving group: Cl is a decent leaving group. Decent LG = S_N2
• Solvent: acetone is a polar aprotic solvent = S_N2
• Substrate: It’s secondary at the leaving group = S_N1 OR S_N2

Almost all of the factors point to an S_N2 reaction, with the notable exception of the type of substrate.  I still feel comfortable saying it is an S_N1 reaction.

What do you think?  What is the most difficult substitution/elimination problem you have seen on an exam or in class?

Reference: E1 E2 SN1 SN2 chart