Reactivity 3.4.9 – Nucleophilic Substitution Reactions of Halogenoalkanes

Nucleophilic substitution is a type of reaction where a nucleophile replaces a leaving group (typically a halogen atom) in an organic compound. Halogenoalkanes (also called haloalkanes or alkyl halides) are particularly reactive toward nucleophilic substitution due to the polar nature of the carbon-halogen bond.

• Nucleophile: A species with a lone pair of electrons that can form a bond by donating its electron pair. Examples include \( \text{OH}^- \), \( \text{CN}^- \), \( \text{NH}_3 \), \( \text{H}_2\text{O} \).
• Leaving Group: An atom or group that can break away from the molecule, taking with it the bonding electrons. In halogenoalkanes, this is typically a halide ion like \( \text{Cl}^- \), \( \text{Br}^- \), or \( \text{I}^- \).

General Reaction Form

\( \text{R-X} + \text{Nu}^- \rightarrow \text{R-Nu} + \text{X}^- \)

Where:

• \( \text{R-X} \) is a halogenoalkane
• \( \text{Nu}^- \) is a nucleophile
• \( \text{X}^- \) is the halide leaving group

Polarity of the Carbon-Halogen Bond

Halogens are more electronegative than carbon, making the C-X bond polar:

\( \delta^+ \text{C} – \text{X} \delta^- \)

This partial positive charge on carbon attracts nucleophiles.

Classification of Halogenoalkanes

• Primary (1°): Carbon attached to the halogen is bonded to only one other carbon.
• Secondary (2°): Carbon attached to the halogen is bonded to two other carbons.
• Tertiary (3°): Carbon attached to the halogen is bonded to three other carbons.

Factors Affecting Reactivity

• Bond Strength: C-I is weaker than C-Br and C-Cl, so iodoalkanes are more reactive than bromo- or chloroalkanes.
• Bond Polarity: C-Cl is more polar than C-Br or C-I, but bond strength plays a more dominant role in reactivity.
• Stability of Leaving Group: A good leaving group is stable after departure – halide ions are generally good leaving groups.

Reactions of Primary and Tertiary Halogenoalkanes with Nucleophiles

• Nucleophilic substitution reactions occur when a nucleophile replaces a halogen atom in a halogenoalkane.
• The mechanism depends on the structure of the halogenoalkane – either SN2 (bimolecular) or SN1 (unimolecular).
• Further, the mechanism of the reaction depends on the type of halogenoalkane:
  • Primary halogenoalkanes – follow the SN2 mechanism (bimolecular)
  • Tertiary halogenoalkanes – follow the SN1 mechanism (unimolecular)
  • Secondary halogenoalkanes – can undergo either mechanism depending on conditions

SN2 Mechanism – Primary Halogenoalkanes

• SN2 stands for Substitution Nucleophilic Bimolecular.
• It is a one-step, concerted mechanism involving simultaneous bond formation and bond breaking.
• The nucleophile attacks the electrophilic carbon from the side opposite the leaving group (back-side attack).
• This forms a transition state in which the carbon is partially bonded to both the nucleophile and leaving group.
• The leaving group is expelled and the nucleophile takes its place in a single step.

Mechanism Example:

\( \text{CH}_3\text{CH}_2\text{Br} + \text{OH}^- \rightarrow \text{CH}_3\text{CH}_2\text{OH} + \text{Br}^- \)

Stereospecific Nature of SN2 Reactions

SN2 reactions are stereospecific, meaning the spatial arrangement of atoms in the product depends directly on the arrangement in the reactant. When the nucleophile attacks the carbon (which is usually attached to four different groups), it does so from the side opposite the leaving group. This results in a complete inversion of configuration around the central carbon atom, often referred to as a Walden inversion.

If the carbon is chiral (has four different groups), the SN2 mechanism causes the product to be the mirror image (enantiomer) of the reactant. This inversion is like an umbrella turning inside out in the wind.

Key points:

• Involves back-side attack by the nucleophile
• Causes inversion of stereochemistry (R to S or S to R)
• Used in synthesis of enantiomerically pure compounds

SN1 Mechanism – Tertiary Halogenoalkanes

• SN1 stands for Substitution Nucleophilic Unimolecular.
• It is a two-step mechanism:
• Step 1 (slow): The halide ion leaves, forming a carbocation intermediate.
• Step 2 (fast): The nucleophile attacks the planar carbocation.
• Because the carbocation is planar, the nucleophile can attack from either side, leading to a racemic mixture if the carbon is chiral.

Mechanism Example:

Step 1: \( (\text{CH}_3)_3\text{CBr} \rightarrow (\text{CH}_3)_3\text{C}^+ + \text{Br}^- \)

Step 2: \( (\text{CH}_3)_3\text{C}^+ + \text{OH}^- \rightarrow (\text{CH}_3)_3\text{COH} \)

Key Characteristics of SN1 Mechanism:

• Carbocation intermediate is stabilized by electron-donating alkyl groups (hence tertiary > secondary > primary).
• If the intermediate is chiral, both enantiomers may form – resulting in a racemic mixture.

Comparison Table: SN1 vs SN2