Steric hindrance in nucleophiles

Key Concepts to Arrange Nucleophile Strength (NEET/JEE)

Nucleophilicity means the ability of a species to donate an electron pair to an electrophile and form a bond. In exams, students must quickly compare nucleophiles using a few core rules.

When we talk about atoms or molecules that have lone-pair electrons, sometimes we call them
bases and sometimes we call them nucleophiles (Table 9.1). What is the difference between a base
and a nucleophile?

Basicity tells us how easily a compound (base) can donate its lone pair of electrons to a proton (H⁺).
A strong base donates its electron pair more easily than a weak base.

Basicity is related to the acid dissociation constant (Ka) of its conjugate acid, which shows how easily that conjugate acid releases a proton. If the conjugate acid releases H⁺ easily, the base is weaker; if it does not release H⁺ easily, the base is stronger.

Nucleophilicity describes how easily a compound (nucleophile) can attack an electron-deficient atom and form a new bond.
It is measured by the rate constant (k), which indicates how fast the nucleophile reacts in a chemical reaction.

Note: Species with a negative charge is a stronger base and a better nucleophile than a
species that has the same attacking atom but is neutral

If the attacking atoms are the same size, stronger bases are better nucleophiles.

−NH2 > HO− > F−

If, however, the attacking atoms of the nucleophiles are very different in size, another factor
comes into play: the polarizability

Effect of Solvent on Nucleophilicity (Simple Point-wise) 🧪

  1. Aprotic Polar Solvent
    (Example: DMSO, DMF, Acetone)
  • Solvent molecules do not contain O–H or N–H bonds.
  • There is no strong hydrogen bonding with nucleophiles.
  • Therefore nucleophiles remain free and reactive.
  • Basicity and nucleophilicity follow the same order.
  • Stronger base → stronger nucleophile.

Example (Halide ions) :F−>Cl−>Br−>I−F^- > Cl^- > Br^- > I^-

  • Here I⁻ is the weakest base, so it is the poorest nucleophile in aprotic solvents.

2. Protic Polar Solvent
(Example: Water, Alcohol)

  • Solvent molecules contain O–H or N–H bonds.
  • They form hydrogen bonding with nucleophiles.
  • Small ions get strongly solvated (surrounded by solvent molecules).
  • This reduces their nucleophilicity.

Result:
Basicity and nucleophilicity order becomes opposite.

Example (Halide ions):I−>Br−>Cl−>F−I^- > Br^- > Cl^- > F^-

  • I⁻ is the best nucleophile in protic solvents because it is large and less solvated.

✅ Quick NEET/JEE Rule

  • Aprotic solvent: Basicity order = Nucleophilicity order
  • Protic solvent: Large atom = Better nucleophile

PROBLEM : Indicate whether each of the following solvents is protic or aprotic: a. chloroform (CHCl3) b. diethyl ether c. acetic acid d. hexane

To classify protic vs aprotic solvents, remember the rule:

Protic solvent: contains H bonded to O, N, or F → can form hydrogen bonding and donate H⁺.
Aprotic solvent: no H attached to O, N, or F.

(a) Chloroform

Structure: CHCl₃

  • Hydrogen is attached to carbon, not O/N/F.
  • Cannot donate hydrogen for hydrogen bonding.

Result: Aprotic solvent

(b) Diethyl ether

Structure: C₂H₅–O–C₂H₅

  • Oxygen is present, but no O–H bond.
  • Hydrogens are attached only to carbon.

Result: Aprotic solvent

(c) Acetic acid

Structure: CH₃–COOH

  • Contains O–H bond in the –COOH group.
  • Can donate proton and form hydrogen bonding.

Result: Protic solvent

(d) Hexane

Structure: alkane

  • Only C–H and C–C bonds.
  • No O–H, N–H, or F–H bonds.

Result: Aprotic solvent

Relative Nucleophilicity toward CH3l in Methanol

PROBLEM: Which is a stronger base: RO– or RS–?

b. Which is a better nucleophile in an aqueous solution?

c. Which is a better nucleophile in DMSO?

Let RO⁻ (alkoxide) and RS⁻ (thiolate) be compared.

Key idea: Basicity and nucleophilicity are not always the same, especially depending on the solvent.

(a) Which is a stronger base?

Compare conjugate acids:

  • RO⁻ → conjugate acid Alcohol (pKa ≈ 16)
  • RS⁻ → conjugate acid Thiol (pKa ≈ 10)

Lower pKa → stronger acid → weaker conjugate base.

Since thiols are more acidic than alcohols, their conjugate base RS⁻ is weaker.

Stronger base: RO⁻

(b) Better nucleophile in aqueous solution (polar protic solvent)

Water is a protic solvent, so small anions are strongly solvated by hydrogen bonding.

  • RO⁻ (O is smaller) → strongly solvated → nucleophilicity decreases
  • RS⁻ (S is larger, more polarizable) → less solvated → more reactive

Better nucleophile in water: RS⁻

(c) Better nucleophile in Dimethyl sulfoxide (polar aprotic solvent)

In polar aprotic solvents, anions are not strongly solvated, so nucleophilicity follows basicity.

Since:

RO⁻ is a stronger base than RS⁻

Better nucleophile in DMSO: RO⁻

Which is stronger nucleophile?

(a) Br⁻ or Cl⁻ in H₂O

Water strongly solvates smaller ions.

Br⁻ is larger → less solvated → more reactive.

Better nucleophile: Br⁻

b. CH₃O⁻ or CH₃OH in H₂O

Charged species are stronger nucleophiles than neutral molecules.

Methoxide ion vs Methanol

Better nucleophile: CH₃O⁻

c. CH₃O⁻ or CH₃OH in DMSO

Same logic: anion >> neutral molecule.

Better nucleophile: CH₃O⁻

(d) Br⁻ or Cl⁻ in DMSO

In aprotic solvent → nucleophilicity follows basicity.

Basicity order:
Cl⁻ > Br⁻

Better nucleophile: Cl⁻

(e) HO⁻ or NH₂⁻ in H₂O

Hydroxide ion vs Amide ion

NH₂⁻ is a much stronger base, but in water it reacts with the solvent:

NH₂⁻ + H₂O → NH₃ + HO⁻

So NH₂⁻ cannot exist effectively in water.

Better nucleophile: HO⁻

(f) I⁻ or Br⁻ in H₂O

In protic solvent → larger ion is better nucleophile.

I⁻ > Br⁻

Better nucleophile: I⁻

(g) I⁻ or Br⁻ in DMSO

Aprotic solvent → nucleophilicity follows basicity.

Basicity:
Br⁻ > I⁻

Better nucleophile: Br⁻

(h) HO⁻ or NH₂⁻ in DMSO

DMSO is aprotic → nucleophilicity follows basicity.

NH₂⁻ is stronger base.

Better nucleophile: NH₂⁻

Nucleophilicity Is Affected by Steric Effects

Basicity Comparison

tert-Butoxide (t-BuO⁻) has three methyl groups pushing electron density toward oxygen.

This increases electron density, making it a stronger base.

Stronger base:(CH3)3CO−  >  CH3CH2O−(CH_3)_3CO^- \; > \; CH_3CH_2O^-

Nucleophilicity Comparison

Nucleophilicity depends strongly on steric hindrance.

  • tert-Butoxide ion is bulky because of three CH₃ groups.
  • This blocks approach to the electrophilic carbon in SN2 reactions.

Ethoxide is smaller, so it can attack carbon more easily.

PROBLEM :
Rank the following species from best nucleophile to poorest nucleophile in an aqueous solution: