Difficulty: Intermediate | Prerequisites: SN1 and SN2 mechanisms (Parts 1 and 2 of these notes), carbocation stability, acid-base chemistry, electronegativity trends, solvent classification.
Big Picture
Knowing the SN1 and SN2 mechanisms is only half the job. The real exam skill is predicting which mechanism will dominate for a given substrate, nucleophile, solvent, and leaving group. This set of notes covers the four key factors that control substitution rates and how to use them to make that prediction. If you are coming in cold, read Parts 1 and 2 first. This material is tested heavily on exams, often in the form of "predict the mechanism and products" or "explain the relative rates" questions.
Four factors determine whether SN1 or SN2 dominates: substrate structure (steric hindrance vs carbocation stability), leaving group ability (weaker bases leave more readily), solvent (polar protic favours SN1, polar aprotic favours SN2), and nucleophile strength (strong nucleophiles push toward SN2; weak ones allow SN1). The mechanism with the lower energy barrier wins.
Steric hindrance
The physical blocking of a reaction site by bulky groups. In SN2, substituents on the electrophilic carbon crowd the back side and slow nucleophilic attack. Think of it as a doorway getting narrower as more groups are bolted to the frame.
Protic solvent
A solvent with a hydrogen attached to a strongly electronegative atom (usually O or N), giving it an acidic proton that can donate hydrogen bonds. Examples: H₂O, CH₃OH, CH₃COOH.
Aprotic solvent
A solvent that cannot donate hydrogen bonds because it lacks an O–H or N–H bond. Examples: DMSO, DMF, acetone, ethers. In simple terms, these solvents leave nucleophiles "unsolvated" and free to attack.
Polar aprotic solvent
An aprotic solvent that is still polar enough to dissolve ionic salts (the source of nucleophiles). The negative charge sits on the solvent's surface, so it solvates cations well, but the positive end is buried, so it does not cage nucleophiles.
Nucleophilicity
A kinetic measure of how quickly a species attacks an electrophilic carbon. Distinct from basicity, which is a thermodynamic measure of how strongly a species bonds to H⁺.
Basicity
A thermodynamic measure of the extent to which a species reacts with H⁺. Stronger bases have higher pKa values for their conjugate acids. For atoms in the same row of the periodic table, stronger base = stronger nucleophile. Down a group, polarisability becomes more important.
Polarisability
How easily an atom's electron cloud can be distorted toward a new bond. Larger atoms (further down the periodic table) are more polarisable, which makes them better nucleophiles because they can begin forming the new bond at a greater distance, stabilising the transition state.
SN2 rate decreases as substitution at the electrophilic carbon increases, because bulkier groups block backside attack.
Relative SN2 rates (with the same nucleophile and leaving group):
Methyl (CH₃–X): relative rate ~30
Primary (RCH₂–X): relative rate ~1
Secondary (R₂CH–X): relative rate ~0.03
Tertiary (R₃C–X): relative rate ~0 (SN2 does not occur)
SN2 also does not occur at sp² carbons (vinyl, aryl) or sp carbons.
SN1 rate increases with greater carbocation stability, which is the reverse pattern:
Tertiary: fastest SN1 (most stable carbocation)
Secondary: moderate SN1 rate
Primary/methyl: SN1 does not occur (carbocation too unstable)
Allylic and benzylic substrates can also undergo SN1 because resonance stabilises their carbocations, even if they are formally primary or secondary.
Methyl and primary substrates: SN2 only
Tertiary substrates: SN1 only (or elimination)
Secondary substrates: could go either way, depending on the other three factors
Leaving group ability affects both SN1 and SN2 in the same direction: a better leaving group speeds up both mechanisms. In both cases, the leaving group acquires negative charge in the transition state, so it helps to be able to stabilise that charge.
The rule of thumb: weaker bases are better leaving groups.
Leaving group ability for the halides: I⁻ > Br⁻ > Cl⁻ >> F⁻.
This tracks inversely with basicity. I⁻ is the weakest base (largest atom, charge most diffuse) and the best leaving group. F⁻ is the strongest base and the worst leaving group.
Strongly basic groups almost never act as leaving groups under normal conditions:
H⁻ (hydride)
CH₃⁻ (carbanion)
OH⁻ (hydroxide)
RO⁻ (alkoxide)
R₂N⁻ (amide)
This is why you cannot directly substitute an OH on an alcohol, or an H on an alkane, with a nucleophile. The leaving group would be too basic. To make OH into a leaving group, it must first be converted to water (by protonation) or to a sulfonate ester (tosylate, mesylate).
The solvent is one of the most important factors in determining SN1 vs SN2, because it affects the two mechanisms in opposite directions.
Protic solvents (H₂O, CH₃OH, CH₃COOH) can donate hydrogen bonds. These H-bonds do two things:
They "cage" anionic nucleophiles by solvating them, which raises the activation energy for SN2 (slower SN2).
They stabilise the developing charges in the SN1 transition state: H-bonds assist leaving group departure (pulling at the departing anion) and the solvent's polarity stabilises the positive charge building on carbon (faster SN1).
So polar protic solvents favour SN1 over SN2.
Polar aprotic solvents (DMSO, DMF, acetone, ethers) cannot donate hydrogen bonds. Their negative ends are exposed on the surface, so they solvate cations well (dissolving nucleophilic salts). But their positive ends are buried and sterically shielded, so they do not cage nucleophiles.
The result: nucleophiles in polar aprotic solvents are "naked" and highly reactive, which dramatically speeds up SN2. Meanwhile, without H-bond assistance for leaving group departure, SN1 is slower.
So polar aprotic solvents favour SN2 over SN1.
SN2: faster in polar aprotic solvents
SN1: faster in polar protic solvents
For SN2 with less basic, more polarisable nucleophiles (e.g. I⁻, RS⁻), protic solvents are tolerable because these nucleophiles are not strongly caged by H-bonds
The nucleophile matters for SN2 but has little effect on SN1.
Because the nucleophile participates in the rate-limiting step of SN2, both its concentration and its reactivity (nucleophilicity) directly affect the rate.
Three trends govern nucleophile strength:
1. Same row of the periodic table: stronger base = stronger nucleophile.
NH₂⁻ > RO⁻ > OH⁻ > RCO₂⁻ > ROH > H₂O
The more electron-rich species donates its lone pair more aggressively.
2. Steric hindrance reduces nucleophilicity.
tert-Butoxide ((CH₃)₃CO⁻) is a strong base but a poor nucleophile because its bulk prevents it from reaching the electrophilic carbon. Ethoxide (CH₃CH₂O⁻) is a weaker base but a stronger nucleophile because it is less hindered.
3. Moving down a group: nucleophilicity increases with size.
I⁻ > Br⁻ > Cl⁻ > F⁻ as nucleophiles.
Larger atoms are more polarisable: their electron clouds distort more easily toward the electrophilic carbon, forming a partial bond at greater distance and stabilising the transition state.
The nucleophile attacks in the fast step of SN1, after the rate-limiting leaving group departure. Even weak nucleophiles (water, alcohols) are reactive enough to attack the highly electrophilic carbocation. Neither the identity nor the concentration of the nucleophile appears in the SN1 rate law.
Students often assume nucleophilicity and basicity are the same thing. They correlate within the same row of the periodic table, but down a group the trend reverses: I⁻ is a far better nucleophile than F⁻, even though F⁻ is the stronger base.
A frequent error is thinking solvent choice does not matter. Changing from a protic to an aprotic solvent can increase SN2 rates by factors of a million or more for basic nucleophiles.
Students sometimes think a good leaving group compensates for a bad substrate. While a better leaving group speeds up both mechanisms, it cannot make SN2 work on a tertiary carbon or SN1 work on a methyl carbon.
Another misconception is that SN1 requires a strong nucleophile. The opposite is true: SN1 typically involves weak, neutral nucleophiles (often the solvent). A strong nucleophile tends to push the reaction toward SN2 instead.
⚠️ "Predict the mechanism" questions are the highest-value application of this material. You will be given a substrate, nucleophile, and solvent and asked whether SN1 or SN2 operates. Systematic evaluation of all four factors is expected.
⚠️ Ranking substrates or nucleophiles in order of reactivity is a common question format.
⚠️ Understanding why solvent choice matters (and being able to explain the mechanism of how protic solvents slow SN2 or speed SN1) is frequently tested.
⚠️ The distinction between nucleophilicity and basicity comes up on virtually every exam covering this chapter.
True or False: Polar aprotic solvents speed up SN1 reactions. (False. They speed up SN2. Polar protic solvents speed up SN1.)
Fill in the blank: Weaker bases make ____ leaving groups. (better)
True or False: tert-Butoxide is both a strong base and a strong nucleophile. (False. It is a strong base but a poor nucleophile due to steric bulk.)
Fill in the blank: The SN2 rate for methyl substrates is ____ than for tertiary substrates. (much faster, or roughly 30x faster than primary; tertiary does not undergo SN2 at all)
True or False: Nucleophile concentration affects the rate of SN1. (False. The SN1 rate depends only on [substrate].)
Q: Predict the mechanism for the reaction of 1-bromobutane with NaCN in DMSO.
A: SN2. The substrate is primary (favours SN2), CN⁻ is a strong nucleophile (favours SN2), and DMSO is a polar aprotic solvent (favours SN2). All four factors point the same way.
Q: Predict the mechanism for the reaction of 2-bromo-2-methylpropane with water.
A: SN1. The substrate is tertiary (cannot do SN2), water is a weak nucleophile (consistent with SN1), and water is a polar protic solvent (favours SN1).
Q: Rank CH₃S⁻, CH₃O⁻, CH₃SH, and CH₃OH from strongest to weakest nucleophile.
A: CH₃S⁻ > CH₃O⁻ > CH₃SH > CH₃OH. Anions are stronger nucleophiles than their neutral counterparts. Sulfur is more polarisable than oxygen, so thiolate beats alkoxide and thiol beats alcohol.
Q: A secondary alkyl bromide is treated with NaOH in water. What mechanism is most likely?
A: This is borderline. OH⁻ is a strong nucleophile (favours SN2), but water is a polar protic solvent (favours SN1), and the substrate is secondary (ambiguous). In practice, this substrate would likely give a mixture of SN2 and E2 products. Switching to DMSO would push it decisively toward SN2.
Q: Why is I⁻ a better nucleophile than F⁻, even though F⁻ is a stronger base?
A: Iodine is much larger and more polarisable than fluorine. Its electron cloud distorts easily toward the electrophilic carbon, forming a partial bond in the transition state at greater distance. This stabilises the transition state and lowers the activation energy. Nucleophilicity (kinetics) and basicity (thermodynamics) diverge down a group.
These same four factors also determine whether elimination (E1 or E2) competes with substitution. Strong bases favour E2 over SN2, particularly with bulky bases and secondary or tertiary substrates. E1 competes with SN1 under the same conditions.
The leaving group ability concepts here carry forward into reactions of alcohols (where OH is converted to a better leaving group via tosylation or protonation) and into acyl substitution in later chapters.
Nucleophilicity trends reappear whenever you need to choose a reagent for a synthesis problem.
SN1 vs SN2, factors affecting substitution rate, substrate structure, steric hindrance, leaving group ability, weak base good leaving group, protic solvent, aprotic solvent, polar aprotic solvent, DMSO, DMF, acetone, hydrogen bonding effect on nucleophile, nucleophilicity vs basicity, nucleophile strength, polarisability, solvation, solvent cage effect, methyl primary secondary tertiary reactivity, halide leaving group ranking, iodide bromide chloride fluoride