R3.4.10 Rate of the substitution reactions (Higher Level Only)

The Influence of the Leaving Group on the Rate of Nucleophilic Substitution Reactions

Understanding the Role of the Leaving Group

What is a Leaving Group?

Definition

Leaving group

A leaving group is an atom or group of atoms that detaches during a substitution reaction.

In nucleophilic substitution reactions, the nucleophile donates an electron pair to the electron-deficient carbon atom of the halogenoalkane, while the leaving group departs with the bonding electrons.

Example

${CH}_{3} {CH}_{2} Cl + {OH}^{-} \to {CH}_{3} {CH}_{2} OH + {Cl}^{-}$

Here, the hydroxide ion ( ${OH}^{-}$ ) replaces the chlorine atom, and the chloride ion ( ${Cl}^{-}$ ) becomes the leaving group.

What Makes a Good Leaving Group?

The effectiveness of a leaving group depends on its ability to stabilize the negative charge it carries after leaving. A good leaving group typically:

Stabilizes the negative charge:
- When the group departs, it takes the bonding electrons, becoming an anion.
- The more stable this anion, the easier it is for the group to leave.
Forms a weak bond with carbon:
- Weaker bonds break more easily, facilitating faster reactions.

Hint

Halide ions (e.g., $F^{-}$ , ${Cl}^{-}$ , ${Br}^{-}$ , $I^{-}$ ) are common leaving groups in halogenoalkanes.
Their leaving ability increases down Group 17 of the periodic table due to decreasing bond strength and increasing anion stability.

Tip

When evaluating leaving groups, prioritize both bond strength and the stability of the anion formed after leaving.

The Rate of Substitution and the Leaving Group

Bond Strength: The Carbon-Halogen Bond

The rate of nucleophilic substitution reactions is closely tied to the strength of the carbon-halogen bond.
Bond strength is measured by bond enthalpy, which represents the energy required to break the bond.
The table below shows the bond enthalpies for carbon-halogen bonds:

$\begin{array}{cc} Bond & Bond Enthalpy (kJ/mol) \\ C - F & 492 \\ C - C l & 324 \\ C - B r & 285 \\ C - I & 228 \end{array}$

From the table, you can see that the C–F bond is the strongest, while the C–I bond is the weakest.
This means that fluoroalkanes are highly resistant to nucleophilic substitution, while iodoalkanes react much more quickly.

Illustration of halogenoalkanes with different leaving groups.

Stability of the Leaving Group

In addition to bond strength, the stability of the halide ion formed as the leaving group plays a critical role.
Larger halide ions, such as $I^{-}$ , are better at dispersing their negative charge due to their size, making them more stable.
This increased stability enhances the likelihood of the halide ion leaving, speeding up the reaction.

Analogy

Think of the leaving group as a parachutist jumping from a plane.
A larger parachute (like the iodide ion) disperses the force of the fall more effectively, making the jump smoother and more likely to succeed.

Predicting Relative Rates of Substitution

Let’s compare the rates of substitution for halogenoalkanes containing different halogens:

Fluoroalkanes ( $C–F$ ):
- The C–F bond is extremely strong, and the fluoride ion ( $F^{-}$ ) is a poor leaving group due to its small size and high charge density.
- As a result, fluoroalkanes are virtually inert in nucleophilic substitution reactions.
Chloroalkanes ( $C–Cl$ ):
- The C–Cl bond is weaker than the C–F bond, and the chloride ion ( ${Cl}^{-}$ ) is a more stable leaving group.
- Chloroalkanes react at a moderate rate.
Bromoalkanes ( $C–Br$ ):
- The C–Br bond is weaker than the C–Cl bond, and the bromide ion ( ${Br}^{-}$ ) is an even better leaving group.
- Bromoalkanes react faster than chloroalkanes.
Iodoalkanes ( $C–I$ ):
- The C–I bond is the weakest, and the iodide ion ( $I^{-}$ ) is the most stable leaving group.
- Iodoalkanes react the fastest in nucleophilic substitution reactions.

Example question

Comparing Reaction Rates

Rank the following halogenoalkanes in order of increasing reaction rate with aqueous sodium hydroxide: ${CH}_{3} {CH}_{2} Cl$ , ${CH}_{3} {CH}_{2} Br$ , ${CH}_{3} {CH}_{2} I$ .

Solution

The rate of reaction increases as the leaving group improves:
${CH}_{3} {CH}_{2} Cl < {CH}_{3} {CH}_{2} Br < {CH}_{3} {CH}_{2} I$
This is because the bond strength decreases and the stability of the leaving group increases from ${Cl}^{-}$ to ${Br}^{-}$ to $I^{-}$ .

Note

In drug development, selecting a halogenoalkane with a good leaving group can significantly affect the efficiency of synthesizing active pharmaceutical ingredients.

Common Mistake

Many students mistakenly believe that the most electronegative halogen (fluorine) always makes the best leaving group. However, bond strength and the stability of the leaving group are far more significant factors than electronegativity.

Reflection

Self review

Why is the iodide ion a better leaving group than the fluoride ion?
How would the rate of substitution change if the nucleophile was weaker, such as water instead of hydroxide?

Theory of Knowledge

How does the concept of a "good leaving group" reflect broader ideas about stability and change in science?
Can these principles be applied to other fields, such as physics or biology?

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