Alkyl Halides and Nucleophilic Substitution (Chapter 6 Study Notes)

Alkyl Halides and Nucleophilic Substitution

Introduction

This chapter explores the structure, nomenclature, physical properties, preparation, and reactions of alkyl halides, with a focus on nucleophilic substitution mechanisms (SN1 and SN2). Alkyl halides are essential intermediates in organic synthesis and are widely used in industry and research.

Halogenated Organic Compounds

Types of Halogenated Compounds

• Alkyl halides: Halogen is directly bonded to an sp3 carbon (e.g., CH3CH2Br, cyclohexyl chloride).

• Vinyl halides: Halogen is bonded to an sp2 carbon of an alkene (e.g., CH2=CHCl).

• Aryl halides: Halogen is bonded to an sp2 carbon on a benzene ring (e.g., bromobenzene).

Polarity and Reactivity

Bond Polarity and Reactivity

• Halogens are more electronegative than carbon, making the C–X bond polar.

• The carbon atom bonded to the halogen has a partial positive charge (δ+), making it susceptible to nucleophilic attack.

• After nucleophilic attack, the halogen leaves with the electron pair, resulting in a substitution reaction.

General equation:

$\ce{Nu^- + R-X -> R-Nu + X^-}$

IUPAC Nomenclature of Alkyl Halides

Naming Rules

• Name as a haloalkane (not as alkyl halide).

• Select the longest carbon chain, even if the halogen is not bonded to the main chain.

• Use the lowest possible numbers for the position of the halogen(s).

Examples:

• 2-chlorobutane: CH3CHClCH2CH3

• 4-(2-fluoroethyl)heptane: CH2FCH2CH2CH2CH2CH2CH3

• 1,3-dichlorocyclohexane

Common Names

• Common names treat the alkyl group as a substituent on the halide (e.g., isopropyl bromide, ethyl bromide).

• Useful mainly for small alkyl groups.

Trivial Names for Methane Derivatives

• CH3Cl: methyl chloride (chloromethane)

• CH2X2: methylene halide (e.g., CH2Cl2: methylene chloride)

• CHX3: haloform (e.g., CHCl3: chloroform)

• CX4: carbon tetrahalide (e.g., CCl4: carbon tetrachloride)

Classification of Alkyl Halides

Types of Alkyl Halides

• Methyl halide: Halide attached to a methyl group (CH3X).

• Primary (1°) alkyl halide: Halogen bonded to a carbon attached to only one other carbon.

• Secondary (2°) alkyl halide: Halogen bonded to a carbon attached to two other carbons.

• Tertiary (3°) alkyl halide: Halogen bonded to a carbon attached to three other carbons.

Types of Dihalides

• Geminal dihalide: Two halogen atoms bonded to the same carbon.

• Vicinal dihalide: Two halogen atoms bonded to adjacent carbons.

Physical Properties of Alkyl Halides

Dipole Moments

• Electronegativity order: F > Cl > Br > I

• Bond length increases as halogen size increases: C–F < C–Cl < C–Br < C–I

• Bond dipole (μ) depends on both bond polarity and length:

C–Cl (1.56 D) > C–F (1.51 D) > C–Br (1.48 D) > C–I (1.29 D)

• Molecular dipole depends on geometry; e.g., CCl4 is nonpolar due to symmetrical bond orientation.

Boiling Points

• Boiling point increases with greater intermolecular forces and higher molar mass.

• London dispersion forces are stronger for larger atoms.

• Spherical shape decreases boiling point.

Alkyl Halide	Boiling Point (K)
CH3F	195
CH3Cl	249
CH3Br	276
CH3I	316

Densities

• Alkyl fluorides and alkyl chlorides (with one Cl) are less dense than water (1.00 g/mL).

• Alkyl chlorides with two or more Cl, all alkyl bromides, and alkyl iodides are denser than water.

Compound	Density (g/mL)
CH3CH2Cl	0.921
CH2Cl2	1.33
CHCl3	1.49
CCl4	1.59
Ethyl bromide	1.47
Ethyl iodide	1.94

Preparation of Alkyl Halides

Free Radical Halogenation

• Halogenation produces a mixture of products; not selective unless all hydrogens are equivalent.

• Chlorination is not selective; bromination is highly selective (3° > 2° > 1° carbons).

Allylic Bromination

• Bromination at the allylic carbon (adjacent to a double bond).

• Mechanism involves free radicals and resonance-stabilized allylic radicals.

• N-Bromosuccinimide (NBS) is used to keep Br2 concentration low.

Example: Cyclohexene + Br2 (light) → 3-bromocyclohexene + HBr

Reactions of Alkyl Halides

Main Reaction Types

• Nucleophilic substitution: Nucleophile replaces the halide (X).

• Elimination: (Covered in Chapter 7) H and halide are removed, forming a double bond.

The SN2 Reaction

Mechanism and Features

• Bimolecular nucleophilic substitution (SN2): one-step, concerted mechanism.

• Rate law: $\text{Rate} = k[\text{alkyl halide}][\text{nucleophile}]$

• Backside attack by nucleophile leads to inversion of configuration (Walden inversion).

• Sensitive to steric hindrance; tertiary halides do not react via SN2.

Energy Diagram

• Single transition state; highest energy point.

• Product is lowest in energy.

Product Classes from SN2

Nucleophile	Product	Class of Product
I-	R–I	Alkyl halide
OH-	R–OH	Alcohol
RO-	R–OR	Ether
SH-	R–SH	Thiol
NH2-	R–NH2	Amine
N3-	R–N3	Azide
CN-	R–CN	Nitrile
Ph3P	R–PPh3	Phosphonium salt

Nucleophilic Strength

• Stronger nucleophiles react faster in SN2 reactions.

• Strong bases are often strong nucleophiles, but not all strong nucleophiles are strong bases (e.g., I-).

Basicity vs. Nucleophilicity

• Basicity: Ability to abstract a proton (H+).

• Nucleophilicity: Ability to attack an electrophilic carbon atom.

Trends in Nucleophilicity

• Negatively charged nucleophiles are stronger than their neutral counterparts.

• Nucleophilicity decreases from left to right across a period.

• Nucleophilicity increases down a group as size and polarizability increase.

Polarizability Effect

• Larger atoms (e.g., I-) are more nucleophilic than smaller ones (e.g., F-) due to greater polarizability.

Solvent Effects

• Protic solvents: Have acidic hydrogens (O–H or N–H) that solvate nucleophiles, reducing nucleophilicity. Nucleophilicity increases with atom size in protic solvents.

• Aprotic solvents: Lack acidic protons; SN2 reactions proceed faster. Examples: acetonitrile, DMF, acetone, DMSO.

Crown Ethers

• Crown ethers solvate cations, increasing the nucleophilic strength of the anion.

• Fluoride becomes a good nucleophile in the presence of crown ethers.

Leaving Group Ability

• Best leaving groups are electron-withdrawing, stable (not strong bases), and polarizable.

• Examples: halides, sulfonates, water.

Effect of Substrate Structure

• Relative rates for SN2: methyl > 1° > 2° >> 3° (tertiary halides do not react via SN2 due to steric hindrance).

Stereochemistry of SN2

• Backside attack leads to inversion of configuration (Walden inversion) at the chiral center.

The SN1 Reaction

Mechanism and Features

• Unimolecular nucleophilic substitution (SN1): two-step mechanism.

• Rate law: $\text{Rate} = k[\text{alkyl halide}]$

• Step 1: Formation of carbocation (slow, rate-determining).

• Step 2: Nucleophile attacks carbocation (fast).

• If nucleophile is neutral, a third step (deprotonation) occurs.

• Carbocation intermediate is planar (sp2 hybridized), allowing attack from either side, leading to racemization if the carbon is chiral.

Carbocation Stability and Rearrangement

• Stability order: 3° > 2° > 1° > methyl

• Carbocations are stabilized by inductive effects and hyperconjugation.

• Rearrangements (hydride or methyl shifts) can occur to form more stable carbocations.

Solvent Effects

• Polar protic solvents are best for SN1 reactions as they stabilize ions via hydrogen bonding.

Stereochemistry of SN1

• Mixtures of enantiomers are produced, usually with more inversion than retention.

Summary Table: SN1 vs. SN2

Feature	SN1	SN2
Order	Unimolecular	Bimolecular
Rate Law	Rate = k[alkyl halide]	Rate = k[alkyl halide][nucleophile]
Intermediate	Carbocation	None (concerted)
Stereochemistry	Racemization (more inversion)	Inversion (Walden inversion)
Substrate Preference	3° > 2° > 1°	Methyl > 1° > 2° >> 3°
Solvent	Polar protic	Polar aprotic
Nucleophile	Weak/neutral	Strong/charged

Uses of Alkyl Halides

• Industrial and household cleaners

• Anesthetics (e.g., chloroform, halothane)

• Freons (refrigerants, now largely replaced due to environmental concerns)

• Pesticides (e.g., DDT)

Practice Problems

• Name and classify alkyl halides using IUPAC and common nomenclature.

• Predict the order of boiling points and densities for various alkyl halides.

• Draw resonance structures for allylic radicals and predict products of free radical halogenation.

• Determine the mechanism (SN1 or SN2) for a given substitution reaction based on substrate, nucleophile, and solvent.

• Predict the stereochemical outcome of nucleophilic substitution reactions.

Additional info: This summary integrates and expands upon the provided lecture slides, ensuring all key concepts from Chapter 6 are covered in a self-contained, exam-oriented format.