Study Notes on Alkyl Halides

Chapter 10: Alkyl Halides

Key Concepts

• Nomenclature for alkyl halides

• Radicals and homolytic cleavage

• Alkane halogenation reaction mechanism

• Relative stability of radicals

• N-bromosuccinimide

Assigned Reading

• Chapter 10, Sections 10.1-10.4

Practice Problems

• Problems: 10-1, 10-2, 10-3, 10-4, 10-5, 10-6, 10-7, 10-14, 10-15, 10-16, 10-18, 10-19, 10-20, 10-21, 10-22 (c), 10-23, 10-24, 10-25, 10-26, 10-30, 10-32, 10-34, 10-39

Nomenclature and Forming Alkyl Halides

• Initiation: Occurs when heat or light causes the bond to break leading to radical formation.
    - Diagram Description:
      - A + B → A• + •B (Homolytic cleavage using heat or light)

• Propagation: A radical reacts with another molecule.
    - Example: A• + C-D → A-C + D•

• Termination: When radicals combine to form stable products.

• General Processes:
    - Initiation → Propagation → Termination

Nomenclature of Alkyl Halides

• Common substituents:
    - Fluoro (F), Chloro (Cl), Bromo (Br), Iodo (I)

• Examples:
    - 1-bromobutane
    - (2)-3-bromo-2-chloro-2-pentene
    - (R)-2-fluorobutane

How to Make Alkyl Halides

1. From Alkenes:
      - Utilizes methods learned in Chapter 6 and technologies from Chapter 8.

2. From Alkanes:
      - Reaction with halogens (X2, typically Br2 or Cl2) and conditions of heat (Δ) or light (hv).
      - Substitution reaction: An atom/group in a compound is replaced by another atom/group.
      - Radical Mechanism:
        - Formation of radicals through homolytic bond cleavage.
        - Comparison with heterolytic bond cleavage.

Radical Chain Mechanism (Step by Step)

• Step 1: Initiation:
     - Example: 2 Br2 → 2 Br• under heat or light becomes radicals.

• Step 2: Chain Propagation:
    - Radical Br• reacts with alkane (e.g., H-C-C-H) continuously forming new radicals while substrate is consumed.

• Step 3: Chain Termination:
    - Two radicals combine to form a stable product (e.g., Br• + H• → HBr).

Carbon-Centered Radical Intermediates

• Stability Order:
    - Tertiary (3°) > Secondary (2°) > Primary (1°) > Methyl

• This stability order is analogous to that of carbocations.

Regioselectivity in Alkane Reactions

• Reaction favors the most stable positions in terms of reactivity, typically tertiary sites:
    - Br2 + heat/light will react to disproportionately favor tertiary radicals compared to secondary or primary.

Stereoselectivity in Halogenation of Alkanes

• Certain reactions involve 50/50 chances of formed products resulting in enantiomers due to the planar nature of radical intermediates.

Allylic Radicals and Stability

• Formation of Allylic Radicals:
    - Allylic radicals are often more stable than secondary or tertiary radicals due to resonance stabilization.
    - General notation: (Allylic > Tertiary > Secondary > Primary > Methyl).

Use of N-Bromosuccinimide (NBS)

• Purpose: Avoids electrophilic addition and controls radical bromination reactions.

• Example Reactions:
    - The product formed from allylic bromination using NBS is usually a compound that could either be mono or poly-substituted.

Reactive Oxygen Species (ROS)

• Definition:
    - Reactive Oxygen Species are comprised of oxygen-centered radicals that can damage organic compounds such as fatty acids.

• Health Implications:
    - ROS are linked to cellular damage and implicated in diseases like cancer.
    - Major sources include mitochondrial activity.

Antioxidants and Their Role

• Vitamin E and BHT (Butylated Hydroxytoluene):
    - Vitamin E is an antioxidant that protects cell membranes from ROS.
    - BHT is used in food preservation to inhibit oxidative degradation.

Expected Outcomes in Radical Reactions

1. Radical mechanism leads to products like 1-bromobutane (anti-Markovnikov).

2. Different products emerge depending on starting materials and mechanisms such as racemic mixtures.

Conclusion and Further Readings

• To enhance understanding, read Chapter 10.4 and practice problems 10-5, 10-6, and 10-7.