Chemistry Notes on Nucleophilic Substitution

Definitions

• Heterolytic fission: A covalent bond breaks, with both electrons going to the same atom.
• Nucleophile: A molecule or negatively charged ion with a lone pair of electrons, attracted to a positively charged region (lower electron density) and donates a lone pair to form a covalent bond. A nucleophile is a Lewis base.
• Substitution reaction: One atom or group is replaced by another.
• Addition reaction: A molecule is added to a compound with a multiple bond without losing any groups.
• Electrophile: A reagent (positive ion or positive end of a dipole) attracted to high electron density regions and accepts an electron pair to form a covalent bond. An electrophile is a Lewis acid.
• Carbocation: An organic molecular species with a positive charge on a carbon atom.

Electron-Pair Sharing Reactions

• Chap 22.1 Nucleophilic substitution reactions
• Chap 22.4 Nucleophilic substitution mechanisms
• SN1 vs SN2

Nucleophilic Substitution of Halogenoalkanes

• Also known as alkyl halides or haloalkanes.

About Halogenoalkanes

• They easily undergo nucleophilic substitution.
  • Nucleophile, Reagent, Conditions:
    • $OH^-$ , $NaOH (aq)$, Heat under reflux
    • $NH<em>2^-$ , $Conc NH</em>3$, Methanol, heat under reflux
    • $CN^-$ , $KCN(aq)$, Heat under reflux

Reaction Mechanisms

• Many apparently simple reactions do not occur in one step but proceed through multiple stages, which constitute the reaction mechanism.

Molecularity

• When analyzing steps in a chemical reaction, there are two primary types of processes:
  • Unimolecular: A single species breaks down into two or more products. Example: $A \rightarrow B + C$ (one reactant)
  • Bimolecular: Two species collide and interact. Example: $X + Y \rightarrow Z + D$ (two reactants)
• Molecularity: The number of species participating in a specific step of the reaction, often referring to the reactant particles in the rate-determining step (rds).

Rate Determining Step (rds)

• The rate-determining step controls the overall reaction rate.

Example

$2H<em>2(g) + 2NO(g) \rightarrow 2H</em>2O(g) + N_2(g)$

• Proposed Mechanism:
  • Step 1: $NO(g) + NO(g) \rightarrow N<em>2O</em>2(g)$ (fast)
  • Step 2: $N<em>2O</em>2(g) + H<em>2(g) \rightarrow N</em>2O(g) + H_2O(g)$ (slow, rds)
  • Step 3: $N<em>2O(g) + H</em>2(g) \rightarrow N<em>2(g) + H</em>2O(g)$ (fast)
  • Overall: $2NO(g) + 2H<em>2(g) \rightarrow N</em>2(g) + 2H_2O(g)$
• If Step 1 is the rate-determining step: $rate = k [NO]^2$, and the order of reaction is zero with respect to hydrogen.
• Given experimental data indicates the rate is first order with respect to $H<em>2$ and second order with respect to $NO$, the rate expression is: $rate = k [H</em>2] [NO]^2$
• The molecularity of the reaction is two, as the rate-determining step involves two species.
• The overall order of the reaction is 3.

Activated Complex

• In a bimolecular process, species collide with necessary activation energy to form an activated complex (transition state).
• An activated complex is not an isolable chemical substance; it's an association of reacting particles where bonds are being broken and formed. It either forms products or reverts to reactants.
• The activated complex is at the peak (maximum) of the energy profile diagram, highly unstable and cannot be isolated, unlike intermediates.

Activated Complexes and Intermediates

Refluxing

• Prolonged heating can cause volatile organic substances to vaporize and escape; a vertical condenser is used to condense the organic vapor.
• Heating organic substances with a flame can be dangerous; electrical heating devices (heating mantles) are preferred.

Rate of Nucleophilic Substitution Reaction

• Halogenoalkanes are classified according to the number of alkyl groups attached to the carbon atom bonded to the halogen. Primary has one alkyl group, secondary has two, and tertiary has three.

SN1 and SN2 Reactions

• In halogenoalkanes, the electron density between the carbon and halogen is greater towards the halogen due to its higher electronegativity, creating a polar molecule with a partial positive charge on carbon and a partial negative charge on the halogen.
• The partial positive charge on the carbon attracts nucleophiles, leading to nucleophilic substitution reactions.
• Common nucleophiles include $OH^-$ (from dilute aqueous hydroxides), $NH_2^-$ (from aqueous ammonia), and $CN^-$ (from cyanides).

SN2 Reaction

• In primary halogenoalkanes, the $δ+$ carbon is surrounded by one alkyl group and two hydrogen atoms, resulting in less steric hindrance, facilitating nucleophile bonding to form an activated complex.
• The rate-determining step involves both the nucleophile and halogenoalkane. The reaction is second order (bimolecular) nucleophilic substitution, SN2.
• $rate = k [Nu^-] [halogenoalkane]$
• The energy profile of the SN2 reaction has only one maximum.

SN1 Reaction

• Step 1: The halide ion ionizes and undergoes heterolytic fission, forming a carbocation.
• Step 2: The carbocation attracts and bonds to a nucleophile.
• Step 1 is the rate-determining step; Step 2 is fast once the carbocation forms. The reaction is a nucleophilic substitution of the first order (unimolecular), SN1.
• $rate = k [halogenoalkane]$
• The energy profile diagram of the SN1 reaction has two maximums because it is a two-step mechanism.

Difference between SN1 and SN2

• Stereochemistry:
  • SN1 reactions form a racemic mixture of both enantiomers.
  • SN2 reactions form only one stereoisomer.

Rate of Nucleophilic Substitution Reaction

• The reaction rate depends on the strength of the halogen-alkane bond: Iodoalkanes react fastest, fluoroalkanes slowest.
• C – F > C – Cl > C – Br > C – I
• Decreasing polarity, decreasing bond strength, increasing reaction rate.

Effect of Nucleophile

• SN1 reactions are unaffected as the nucleophile isn't in the rate expression.
• SN2 reactions proceed faster with negative ions like $OH^-$ instead of $H_2O$ due to stronger attraction. SN1 proceeds faster than SN2 with aqueous $NaOH$.

SN1 or SN2 Reaction?

• Steric hindrance prevents tertiary halogenoalkanes from undergoing SN2.
• Alkyl groups in tertiary halogenoalkanes stabilize the carbocation via positive inductive effect (electron releasing).
• Primary halogenoalkanes usually undergo SN2 reactions.
• Secondary halogenoalkanes can undergo both SN1 and SN2 reactions.

Dichotomy of Solvents

• Non-polar (e.g., cyclohexane, $CCl_4$)
• Polar
  • Protic (e.g., $H<em>2O$, $NH</em>3$)
  • Aprotic (e.g., $CHCl<em>3$, $CH</em>3COCH_3$)

Effect of Solvent on SN1 and SN2

• SN1 reactions are favored by polar protic solvents because they stabilize the ions formed. Polar aprotic solvents may form products with intermediate carbocations.
• SN2 reactions are favored by non-polar aprotic solvents.

Nucleophilic Substitution Reactions General reaction

$CH<em>3CH</em>2CH<em>2Br + NaOH \rightarrow CH</em>3CH<em>2CH</em>2OH + NaBr$
Ionic equation
$CH<em>3CH</em>2CH<em>2Br + OH^- \rightarrow CH</em>3CH<em>2CH</em>2OH + Br^-$

Dominant mechanism

• Primary halogenoalkanes: SN2
• Tertiary halogenoalkanes: SN1

The effect of the halogen (leaving group) on the rate of nucleophilic substitution

R–I > R–Br > R–Cl > R–F
weaker bond = faster reaction