Chapter 6: Alkyl Halides and Nucleophilic Substitution – Study Notes

Chapter 6: Alkyl Halides; Nucleophilic Substitution

6-1 Introduction

Halogenated organic compounds are classified into three major classes based on the type of carbon to which the halogen is bonded. These compounds play important roles in organic synthesis and have various applications.

• Alkyl halides: Halogen atom bonded to a sp3 hybrid carbon atom of an alkyl group.

• Vinyl halides: Halogen atom bonded to one of the hybrid carbon atoms of an alkene.

• Aryl halides: Halogen atom bonded to a carbon atom of an aromatic ring.

Example: Chloromethane (CH3Cl) is a simple alkyl halide used as a solvent.

6-1 Properties of Alkyl Halides

Alkyl halides possess unique physical and chemical properties due to the presence of a polar carbon-halogen bond.

• Polarity: The carbon-halogen bond is polar because halogens are more electronegative than carbon.

• Bond Polarization: Most reactions of alkyl halides result from breaking this polarized bond.

• Leaving Group: Halogen can act as a leaving group, taking the bonding pair of electrons with it.

• Elimination: Halogen can be eliminated from the alkyl halide.

• Substitution: Halogen can be replaced by a wide variety of functional groups.

Example: The electron potential map (EPM) of chloromethane shows the partial charges on the atoms.

6-2 Nomenclature of Alkyl Halides

Alkyl halides are named using IUPAC and common naming conventions.

• IUPAC: Treats an alkyl halide as an alkane with a halo- substituent (e.g., fluoro-, chloro-, bromo-, iodo-).

• Common names: Name the alkyl group first, then the halide (e.g., isopropyl bromide).

Halogen	Symbol
Fluorine	F
Chlorine	Cl
Bromine	Br
Iodine	I

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

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

Alkyl halides are further classified by the nature of the carbon atom bonded to the halogen:

• Primary (1°) halide: Halogen-bearing carbon bonded to one carbon atom.

• Secondary (2°) halide: Halogen-bearing carbon bonded to two carbon atoms.

• Tertiary (3°) halide: Halogen-bearing carbon bonded to three carbon atoms.

• Methyl halide: Halogen-bearing carbon is a methyl group.

6-3 Common Uses of Alkyl Halides

Alkyl halides have a variety of practical applications:

• Solvents: Used in industrial and household cleaning and degreasing (e.g., CH2Cl2, CHCl3).

• Reagents: Serve as starting materials for synthesizing more complex molecules.

• Anesthetics: Ethyl chloride (CH3CH2Cl) is used as a topical anesthetic.

• Pesticides: DDT is a well-known pesticide, though toxic to mammals.

• Refrigerants and Foaming Agents: Freons (CFCs) were developed to replace ammonia as refrigerants.

6-4 Structure of Alkyl Halides

The structure of alkyl halides is defined by the bonding of the halogen atom to a sp3 hybrid carbon atom.

• Electronegativity: Halogen is more electronegative than carbon, polarizing the C–X bond.

• Dipole Moment: The dipole moment ($\mu$) is given in Debyes (D): $\mu = 4.8 \times \delta \times d$ where $\delta$ is the amount of charge separation and $d$ is the bond length.

6-5 Physical Properties of Alkyl Halides

Physical properties such as boiling points are influenced by the nature of the halogen and the structure of the molecule.

• Electronegativity: Decreases down the group: F > Cl > Br > I.

• C–X Bond Lengths: Increase as the halogen atom becomes larger:

  Bond	Length (Å)
  C–F	1.38
  C–Cl	1.78
  C–Br	1.94
  C–I	2.14

• Boiling Points: Molecules with larger surface area and higher molecular weight have higher boiling points. Boiling points of ethyl halides increase in the order: C2H5F < C2H5Cl < C2H5Br < C2H5I.

6-6 Preparation of Alkyl Halides

Alkyl halides can be prepared by free-radical halogenation, though this method is not always selective.

• Free-Radical Halogenation: Involves the reaction of alkanes with halogens under light (hv) to produce alkyl halides.

• Mixtures of products are often obtained, and selectivity is low.

Allylic Bromination

Allylic bromination is a selective process where bromine substitutes for a hydrogen atom at the allylic position (next to a C=C double bond).

• Allylic intermediates: Stabilized by resonance with the double bond.

• Bromination: Highly selective, forming the most stable allylic radical.

• Mechanism: Often uses N-bromosuccinimide (NBS) as the bromine source to maintain low bromine concentration.

Example: Free-radical bromination of cyclohexene yields 3-bromocyclohexene.

6-7 Reactions of Alkyl Halides: Substitution and Elimination

Alkyl halides undergo two main types of reactions: substitution and elimination.

• Substitution: Another atom replaces the halide ion. Halide acts as a good leaving group.

• Nucleophilic Substitution: Nucleophile replaces a leaving group from a carbon atom to form a new bond.

• Types: SN1 (unimolecular) and SN2 (bimolecular).

• Elimination: Halide ion leaves along with another atom or ion (often H+), forming a new pi bond and resulting in an alkene.

6-8 Bimolecular Nucleophilic Substitution: SN2 Reaction

The SN2 reaction is a concerted, bimolecular process where a nucleophile attacks an electrophilic carbon, displacing the leaving group.

• Nucleophile: Electron-rich species with unshared pairs of electrons and a negative charge.

• Substrate: Compound that is attacked by the nucleophile.

• Electrophile: Carbon atom bonded to an electronegative atom.

• Leaving Group: Displaced as a stable species.

SN2 Reaction Mechanism

• Concerted Mechanism: Reaction occurs in a single step with a single transition state.

• Back-side Attack: Nucleophile attacks the back side of the electrophilic carbon atom, leading to inversion of configuration.

• Transition State: Five-coordinate carbon atom with two partial bonds.

• Exothermic Reaction: Bond forming and breaking occur simultaneously.

Example Equation: $\text{Rate} = k[\text{Alkyl Halide}][\text{Nucleophile}]$

Kinetics of SN2 Reaction

• Bimolecular: Both substrate and nucleophile are present in the transition state.

• Second Order: Overall rate depends on the concentrations of both reactants.

Generality of the SN2 Reaction

Nucleophiles can convert alkyl halides to a wide variety of functional groups.

Nucleophile	Product	Class of Product
I-	R–I	Alkyl halide
OH-	R–OH	Alcohol
OCH3-	R–OCH3	Ether
SH-	R–SH	Thiol
CN-	R–CN	Nitrile

6-10 Factors Affecting SN2 Reactions

Several factors influence the rate and outcome of SN2 reactions:

• Strength of the Nucleophile: Determined by charge, electronegativity, steric effects, and solvent effects.

• Structure of the Alkyl Halide: Less steric hindrance increases reactivity.

• Stability of the Leaving Group: Good leaving groups are weak bases, typically conjugate bases of strong acids.

Strength of the Nucleophile: Charge

• A species with a negative charge is a stronger nucleophile than a neutral species.

• A base is always a stronger nucleophile than its conjugate acid.

Basicity vs. Nucleophilicity

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

• Nucleophilicity: Ability to donate electrons to an electrophile.

• Basicity and nucleophilicity are related but distinct properties.

Nucleophilicity: Electronegativity

• Nucleophilicity decreases from left to right in the periodic table as electronegativity increases.

• More electronegative elements hold electrons more tightly, reducing nucleophilicity.

Steric Effects on Nucleophilicity

• Steric hindrance decreases nucleophilicity; bulky nucleophiles cannot easily approach the carbon atom.

• Steric hindrance has less effect on basicity.

Solvent Effects on Nucleophilicity

• Polar, protic solvents: Can form hydrogen bonds with nucleophiles, stabilizing them and decreasing nucleophilicity.

• Polar, aprotic solvents: Lack N–H and O–H bonds, do not stabilize nucleophiles as much, enhancing nucleophilicity.

6-11 Reactivity of the Substrate

The structure of the alkyl halide affects its reactivity toward nucleophilic attack.

• Substrate must have an electrophilic carbon atom with a good leaving group.

• Carbon atom must not be too sterically hindered.

• Relative rates for SN2: CH3X > 1° > 2° > 3° (methyl halide is most reactive, tertiary is least).

6-11 Leaving Group

Leaving groups play a crucial role in substitution reactions.

• Good leaving groups are weak bases (conjugate bases of strong acids).

• Strong bases make poor leaving groups.

• Some neutral molecules (e.g., water, alcohols) can also serve as leaving groups.

6-12 Stereochemistry

SN2 reactions require attack by a nucleophile on the back side of an electrophilic carbon atom, resulting in inversion of configuration.

• Inversion of Configuration: Product has the opposite configuration to the substrate.

• Example: (R)-2-bromobutane reacts to form (S)-2-butanol via SN2 mechanism.

Practice Problems

• Draw structures and give IUPAC names for various alkyl halides.

• Predict boiling points and substitution products.

• Rank compounds by reactivity toward SN2 reactions.

• Draw mechanisms for allylic bromination and nucleophilic substitution.

Additional info: These notes expand on brief slide points with definitions, examples, and academic context for clarity and completeness.