In organic chemistry, a nucleophilic substitution reaction happens when a nucleophile (an electron-rich chemical species) replaces a “leaving group” on an electrophile (an electron-poor chemical species). Think of it like a chemical switcheroo.
There are two main ways that these substitutions can occur: SN1 and SN2 reactions. These two reactions differ in several ways, including their mechanisms, kinetics, and stereochemical outcomes.
In this article, we’ll break down the differences between SN1 vs SN2 reactions. We’ll explore their mechanisms, rate laws, and the factors that influence their rate and stereochemistry.
Core Concepts and Mechanisms
Both SN1 and SN2 reactions result in a nucleophile replacing a leaving group, but they do so through different mechanisms.
SN1 Mechanism
SN1 reactions proceed in two steps and involve the formation of a carbocation. First, the leaving group separates from the carbon atom, forming a carbocation intermediate. This ionization step determines the overall rate of the reaction.
Whether an SN1 reaction occurs depends on the stability of the carbocation intermediate. Tertiary carbocations are more stable than secondary, which are, in turn, more stable than primary carbocations.
SN2 Mechanism
SN2 reactions occur in a single, concerted step with a bimolecular transition state.
SN2 reactions involve what’s known as “backside attack,” and this typically results in an inversion of the configuration at the chiral center.
Rate Equations
The rate of an SN1 reaction depends only on the concentration of the electrophile (substrate). The rate equation is:
Rate = k[Electrophile]
This is because the rate-determining step is the formation of the carbocation.
The rate of an SN2 reaction depends on the concentrations of both the electrophile (substrate) and the nucleophile. The rate equation is:
Rate = k[Electrophile][Nucleophile]
This is because both the nucleophile and substrate are involved in the single, concerted step.
Electrophile Structure
The structure of the electrophile—the molecule that’s attacked by the nucleophile—plays a big role in determining whether an SN1 or SN2 reaction is more likely to occur.
SN1 Electrophiles
SN1 reactions prefer tertiary alkyl halides, as well as allylic and benzylic halides. This is because these structures can form relatively stable carbocations, which are essential intermediates in the SN1 mechanism.
Primary and methyl halides, on the other hand, don’t work well with SN1 reactions. The carbocations that would form from these structures are simply too unstable to form easily.
SN2 Electrophiles
SN2 reactions favor methyl and primary alkyl halides. The key here is steric hindrance—the “crowding” around the reaction site.
Primary carbons are less sterically hindered, so the nucleophile can attack more easily. Tertiary carbons, with their bulky groups, have significant steric hindrance, making SN2 reactions much slower or even impossible.
Nucleophile Strength
The strength of the nucleophile involved plays a significant role in determining whether an SN1 or SN2 reaction will occur.
SN1 Nucleophiles
SN1 reactions tend to favor weak nucleophiles. In fact, a special case of SN1, called solvolysis, happens when the solvent itself acts as the nucleophile.
SN2 Nucleophiles
SN2 reactions, on the other hand, are faster and more efficient when strong nucleophiles are involved.
Generally, stronger bases make better nucleophiles, but that’s not always the case. Steric factors and the solvent used can sometimes influence the relationship between nucleophilicity and basicity.
Solvent Effects
The type of solvent used in a reaction can significantly influence whether an SN1 or SN2 reaction will be favored.
SN1 Solvents
SN1 reactions thrive in polar protic solvents. These solvents, like water and alcohols, have hydrogen atoms that can form hydrogen bonds. This is important because polar protic solvents stabilize the carbocation intermediate formed during an SN1 reaction through a process called solvation.
SN2 Solvents
SN2 reactions, on the other hand, are best performed in polar aprotic solvents. These solvents, such as acetone and DMSO, are polar but lack hydrogen atoms available for hydrogen bonding. Polar aprotic solvents enhance the nucleophilicity of the nucleophile because they don’t solvate it as strongly, allowing it to attack the substrate more effectively.
Leaving Group Ability
Both SN1 and SN2 reactions require a “leaving group,” a molecular fragment that departs the molecule with a pair of electrons.
The best leaving groups are weak bases. That’s because weak bases are more stable when they take off with an electron pair.
Some common leaving groups include halides (Cl–, Br–, I–), water (H2O), and tosylates (OTs).
Frequently Asked Questions
What is the difference between SN1 and SN2 reactions?
SN1 reactions are unimolecular, involving two steps: the leaving group departs first, forming a carbocation intermediate, followed by nucleophilic attack. SN2 reactions are bimolecular, occurring in a single, concerted step where the nucleophile attacks as the leaving group departs. SN1 favors tertiary carbons, while SN2 prefers primary carbons.
What is the difference between SN1 and SN2 alcohol reactions?
Alcohols themselves aren’t good substrates for SN1 or SN2. They must first be converted into a better leaving group, like a tosylate or a protonated alcohol. Once that’s done, the reaction pathway (SN1 or SN2) then depends on the substitution of the carbon bearing the leaving group, and the solvent. SN1 reactions of alcohols are favored by protic solvents and tertiary alcohols, while SN2 reactions are favored by aprotic solvents and primary alcohols.
How do I know if a reaction is SN1 or SN2?
Several factors influence the reaction mechanism. Consider the structure of the alkyl halide or alcohol derivative (primary, secondary, tertiary), the strength of the nucleophile, and the solvent (polar protic vs. polar aprotic). Tertiary substrates in polar protic solvents generally favor SN1, while primary substrates with strong nucleophiles in polar aprotic solvents favor SN2.
Why does SN1 happen instead of SN2?
SN1 reactions are favored when the substrate is sterically hindered, preventing the nucleophile from attacking in a single step. The formation of a stable carbocation intermediate is also crucial for SN1. Additionally, polar protic solvents stabilize the carbocation intermediate, further promoting SN1 over SN2.
Putting It All Together
SN1 and SN2 reactions are fundamentally different in their mechanisms, rate laws, stereochemistry, and the factors that speed them up or slow them down.
When you’re trying to predict whether a substitution reaction will proceed via SN1 or SN2, you have to consider the electrophile, the nucleophile, and the solvent. These factors can all influence which reaction pathway is more favorable.
It’s worth remembering that secondary alkyl halides can participate in both SN1 and SN2 reactions, and the reaction that actually occurs will depend on the specific conditions of the reaction.