Chapter 12: Substitution and Elimination Reactions – Mechanisms, Stereochemistry, and Comparisons

Substitution and Elimination Reactions

Introduction to Reaction Types

Organic reactions can be classified into three main types: addition, substitution, and elimination. Substitution and elimination reactions are fundamental processes in organic chemistry, especially for alkyl halides.

• Addition (synthesis): Two reactants combine to form a single product. Example: $\ce{HCl}$ adds to ethene.

• Substitution (double replacement): An atom or group in a molecule is replaced by another atom or group. Example: Methoxy group substitutes for chlorine in $\ce{CH3CH2Cl}$.

• Elimination (decomposition): Atoms or groups are removed from a molecule, often forming a double bond. Example: $\ce{HBr}$ is eliminated from 2-bromobutane.

Substitution vs. Elimination

Key Differences

Substitution reactions involve the replacement of a leaving group by another atom or group, while elimination reactions result in the removal of a leaving group and a hydrogen from an adjacent carbon, forming a double bond.

• Substitution: $\ce{RCH2CH2X + Y^- \rightarrow RCH2CH2Y + X^-}$

• Elimination: $\ce{RCH2CH2X + Y^- \rightarrow RCH=CH2 + HY + X^-}$

Substitution Reactions

Mechanisms: $\mathrm{S_N1}$ and $\mathrm{S_N2}$

Substitution reactions can proceed via two main mechanisms: $\mathrm{S_N1}$ (unimolecular nucleophilic substitution) and $\mathrm{S_N2}$ (bimolecular nucleophilic substitution).

• S: substitution

• N: nucleophilic

• 1 or 2: unimolecular or bimolecular (number of molecules involved in the rate-determining step)

Mechanistic Possibilities

For a typical substitution (e.g., $\ce{CH3CH2Cl}$ with $\ce{CH3O^-}$):

• Possibility 1: Nucleophile attacks first, then leaving group departs ($\mathrm{S_N2}$).

• Possibility 2: Leaving group departs first, forming a carbocation, then nucleophile attacks ($\mathrm{S_N1}$).

• Possibility 3: Simultaneous attack and departure ($\mathrm{S_N2}$, concerted mechanism).

$\mathrm{S_N2}$ Reaction Mechanism

Mechanism and Features

The $\mathrm{S_N2}$ reaction is a one-step, concerted process where the nucleophile attacks the substrate as the leaving group departs.

• Rate law: $\text{rate} = k[\ce{RX}][\text{nuc}]$

• Stereochemistry: Inversion of configuration (backside attack).

• Transition state: Both nucleophile and leaving group are partially bonded.

Factors Affecting $\mathrm{S_N2}$

• Alkyl halide size: Smaller (less hindered) alkyl halides react faster.

• Nucleophile strength: Stronger bases are better nucleophiles.

• Halide reactivity: $\ce{RI} > \ce{RBr} > \ce{RCl} > \ce{RF}$ (iodide is best leaving group).

Relative Rates Table

Nuc	Product	Relative rate of $\mathrm{S_N2}$ reaction
$\ce{H2O}$	$\ce{H3COCH3}$	1
$\ce{HC\equiv CO^-}$	$\ce{CH3COCH3}$	500
$\ce{NH2^-}$	$\ce{H3CNH2}$	700
$\ce{OH^-}$	$\ce{H3COH}$	10,000
$\ce{CH3O^-}$	$\ce{H3COCH3}$	23,000
$\ce{F^-}$	$\ce{H3COF}$	100,000
$\ce{CN^-}$	$\ce{H3COCN}$	125,000
$\ce{SH^-}$	$\ce{H3COSH}$	121,000

Solvent Effects

Polar protic	Polar aprotic
water	tetrahydrofuran (THF)
ethanol	dimethyl sulfoxide (DMSO)
acetic acid	acetone

• Polar aprotic solvents: Favor $\mathrm{S_N2}$ by not solvating nucleophiles strongly.

• Polar protic solvents: Favor $\mathrm{S_N1}$ by stabilizing ions.

$\mathrm{S_N1}$ Reaction Mechanism

Mechanism and Features

The $\mathrm{S_N1}$ reaction proceeds via a two-step mechanism: first, the leaving group departs, forming a carbocation; then, the nucleophile attacks the carbocation.

• Rate law: $\text{rate} = k[\ce{RX}]$

• Carbocation stability: Tertiary > secondary > primary

• Stereochemistry: Can produce both retention and inversion (racemization possible).

• Solvolysis: Solvent acts as nucleophile.

Carbocation Rearrangements

• Rearrangements: Methyl or hydride shifts can occur to form more stable carbocations.

• Resonance: Delocalization of positive charge can stabilize carbocation intermediates.

Solvent Effects

• Polar protic solvents: Stabilize carbocations and favor $\mathrm{S_N1}$ reactions.

Comparison Table: $\mathrm{S_N1}$ vs. $\mathrm{S_N2}$

Characteristic	$\mathrm{S_N2}$	$\mathrm{S_N1}$
Mechanism	One-step, bimolecular	Two-step, carbocation intermediate
Rate law	$k[\ce{RX}][\text{nuc}]$	$k[\ce{RX}]$
Stereochemistry	Inversion	Retention and inversion
Leaving group	$\ce{I^-} > \ce{Br^-} > \ce{Cl^-} > \ce{F^-}$	$\ce{I^-} > \ce{Br^-} > \ce{Cl^-} > \ce{F^-}$
Alkyl halide reactivity	methyl, primary, secondary	tertiary
Nucleophile strength	Strong	Not important
Solvent	Polar aprotic	Polar protic

Elimination Reactions

Mechanisms: E1 and E2

Elimination reactions remove a leaving group and a hydrogen from adjacent carbons, forming a double bond. Two main mechanisms exist: E1 (unimolecular) and E2 (bimolecular).

• E: elimination

• 1 or 2: unimolecular or bimolecular (number of molecules in rate-determining step)

E2 Reaction Mechanism

Mechanism and Features

The E2 reaction is a one-step, concerted process where a base removes a proton from the beta-carbon as the leaving group departs from the alpha-carbon, forming a double bond.

• Rate law: $\text{rate} = k[\ce{RX}][\text{base}]$

• Dehydrohalogenation: Removal of hydrogen and halogen.

• Preferred with: Strong bases, polar aprotic solvents, primary alkyl halides.

Zaitsev's Rule

The major alkene product is the more substituted alkene, formed by removing the hydrogen from the beta-carbon with the fewest hydrogens.

Anti-Zaitsev Products

• Bulky bases or conjugated systems can lead to less substituted (anti-Zaitsev) alkenes.

Stereochemistry for E2

Geometric Requirements

E2 reactions require the H-C-C-X atoms to be coplanar. Anti elimination (staggered conformation) is preferred over syn elimination (eclipsed conformation).

• Anti elimination: Back-side attack, major product.

• Syn elimination: Front-side attack, less common.

Product Stereochemistry

• If the beta-carbon has two hydrogens, two alkenes can form; the major product has the largest substituents on opposite sides.

• If the beta-carbon has one hydrogen, only one alkene forms, with configuration based on the alkyl halide.

E1 Reaction Mechanism

Mechanism and Features

The E1 reaction proceeds via a two-step mechanism: first, the leaving group departs, forming a carbocation; then, a base removes a proton from the beta-carbon, forming a double bond.

• Rate law: $\text{rate} = k[\ce{RX}]$

• Carbocation rearrangements: Possible due to carbocation intermediate.

• Preferred with: Weaker bases, polar protic solvents, tertiary alkyl halides.

Stereochemistry for E1

• Both E and Z isomers can form; E (opposite sides) is usually the major product.

Comparisons and Summary Tables

Comparing $\mathrm{S_N1}$ and E1

• Both can form mixtures of products; conditions determine which pathway is favored.

• Substitution is favored with weak bases; elimination is favored at higher temperatures.

Comparing $\mathrm{S_N2}$ and E2

Entry	Characteristic	Observation	Example
1	1° alkyl halide	With very little steric hindrance, substitution is favored.	Example: $\ce{CH3CH2Br}$
2	2° alkyl halide	With more hindrance, elimination is the only possibility.	Example: $\ce{CH3CHBrCH3}$
3	Bulky base/nucleophile	Bulky nucleophiles require more space to approach; likely favor elimination.	Example: $\ce{(CH3)3CO^-}$
4	Small base/nucleophile	Small nucleophiles can attack easily; substitution is favored.	Example: $\ce{OH^-}$
5	Branching near leaving group	Branching restricts access near halogen; elimination is favored.	Example: $\ce{(CH3)2CHCH2Br}$
6	2° alkyl halide/weak base	There is some steric hindrance, allowing slow substitution, but not enough to promote elimination.	Example: $\ce{CH3CHBrCH3}$

Stereochemistry Table for E1 and E2

Reaction	Products
$\mathrm{S_N2}$	Only the inverted product is formed.
E2	Both E and Z isomers are formed (with more of the stereoisomer with the largest groups on opposite sides of the double bond) unless the beta-carbon from which the hydrogen is removed is bonded to only one hydrogen, in which case only one stereoisomer is formed. The stereoisomer's configuration depends on the configuration of the reactant.
$\mathrm{S_N1}$	Both stereoisomers (R and S) are formed (generally with more inverted product than retained).
E1	Both E and Z stereoisomers are formed (with more of the stereoisomer with the largest groups on opposite sides of the double bond).

Key Terms and Concepts

• Nucleophile: Species that donates an electron pair to form a new bond.

• Leaving group: Atom or group that departs with an electron pair in substitution/elimination.

• Carbocation: Positively charged carbon intermediate, important in $\mathrm{S_N1}$ and E1.

• Zaitsev's rule: Major alkene product is the more substituted alkene.

• Solvolysis: Reaction where the solvent acts as the nucleophile.

Example: In the $\mathrm{S_N2}$ reaction of $\ce{CH3CH2Br}$ with $\ce{OH^-}$, ethanol is formed with inversion of configuration.

Example: In the E2 reaction of $\ce{CH3CH2CHBrCH3}$ with $\ce{CH3O^-}$, 2-methyl-2-butene is the major product (Zaitsev's rule).

Additional info: These notes expand on the provided slides by clarifying mechanistic details, adding definitions, and summarizing key tables for comparison and stereochemistry.