The SN2 Mechanism
Last updated: January 23rd, 2020 |
The SN2 Reaction Mechanism
Having gone through the two different types of substitution reactions, and talked about nucleophiles and electrophiles, we’re finally in a position to reveal the mechanism for one of the most important reactions in organic chemistry.
It’s called the SN2 reaction, and it’s going to be extremely useful for us going forward.
Table of Contents
- The SN2 Reaction Proceeds With Inversion of Configuration
- The Rate Law Of The SN2 Is Second Order Overall
- The Reaction Rate Is Fastest For Small Alkyl Halides (Methyl > Primary > Secondary >> Tertiary)
- The SN2 Mechanism Proceeds Through A Concerted Backside Attack Of The Nucleophile Upon The Alkyl Halide
When we start with a molecule with a chiral center, such as (S)-2-bromobutane, this class of reaction results in inversion of stereochemistry. Note how we start with (S)-2-bromobutane and end up with (R)-2-methylbutanenitrile.
Note how the rate of the reaction is dependent on both the concentration of the nucleophile and that of the substrate. In other words, it’s a second-order reaction.
3. The Reaction Rate Of The SN2 Reaction Is Fastest For Small Alkyl Halides (Methyl > Primary > Secondary >> Tertiary)
Finally, note how changes in the substitution pattern of the alkyl halide results in dramatic changes in the rate of the reaction.* “Smaller” alkyl halides like methyl bromide are fast, while more highly substituted tertiary alkyl bromide doesn’t proceed at all.
Taking all this data into consideration, we refer to this reaction as the SN2 mechanism. What does SN2 stand for?
- 2 molecules in the rate determining step
So how does it work?
4. The SN2 Mechanism Proceeds Through A Concerted Backside Attack Of The Nucleophile Upon The Alkyl Halide
The best explanation we have for what happens in this reaction is that it proceeds through what organic chemists refer to as a backside attack. The nucleophile approaches the alkyl halide 180° from the C-Br bond, and as the C-(nucleophile) bond forms, the C-(leaving group) bond breaks.** At the transition state of the reaction, there are partial C-(nucleophile) and C-(leaving group) bonds (denoted by dashed lines). Note the geometry too – instead of tetrahedral, it’s trigonal bipyramidal. This is 5-coordinate carbon – if only for a femtosecond or two.
And in an analogy you’ll no doubt hear many times, then, like an umbrella in a strong wind, the three groups flip over as the leaving group leaves, resulting in inversion of configuration. Note that inversion happens at carbons without stereocenters too – it’s just that we can’t observe it because there’s no way to detect the change in configuration.
This umbrella metaphor for the backside attack mechanism is so fundamental and well known in organic chemistry that you can tweet about it and people will know exactly what you mean.
In the next post, we’ll show some more examples of this reaction and explain why it’s one of the most useful reactions in chemistry.
P.S. You may remember that Freda also took this awesome picture of an ozonolysis reaction.
*Numbers are approximate. Source – Smith, M. and March, J. L. “March’s Advanced Organic Chemistry” 5th ed.
** backside attack, because the nucleophile donates a pair of electrons into the most accessible empty orbital, which is the antibonding (σ*) orbital of the C-(leaving group) bond, which resides at 180° to the bond. Donation of a pair of electrons into the antibonding orbital results in cleavage of the bond. It’s kind of like an “eject button” in that way.
(Advanced) References and Further Reading
- Solvolytic Displacement Reactions At Saturated Carbon Atoms
Andrew Streitwieser, Jr.
Chemical Reviews 1956 56 (4), 571-75
This early review by Prof. Streitwieser (U.C. Berkeley) is a comprehensive review of the early literature of the SN1 and SN2 reactions.