Chapter 10 — Organohalides: Notes, Flashcards, and Practice Test Summary & Study Notes

🔬 Introduction to Organohalides

Organohalides are organic compounds that contain one or more halogen atoms (F, Cl, Br, I) bonded to carbon. They are important in pharmaceuticals, materials, and environmental chemistry because halogens often make molecules lipophilic, reactive, and able to act via multiple mechanisms. Halogens are good leaving groups, which explains much of organohalide reactivity.

🧭 Nomenclature Rules

Follow standard IUPAC rules: (1) identify the longest carbon chain containing the principal functional group; (2) assign lowest locants to substituents; (3) use alphabetical order for substituent ties. For halogen substituents use prefixes fluoro-, chloro-, bromo-, iodo- and include locants for stereodescriptors when needed.

⚛️ Radical Stability and Identification

Radical stability trends (general): vinylic < primary < secondary < tertiary < allylic/benzylic. Stabilization arises from hyperconjugation (alkyl donation into the radical center) and resonance (allylic/benzylic delocalization). Radical geometry is typically trigonal planar at the radical center.

🔥 Radical Chain Mechanism: Steps

Radical reactions follow three key steps: Initiation (generate radicals, often by homolysis via light $h\nu$ or heat $\Delta$), Propagation (radicals react to form new radicals; repeated chain steps), and Termination (radical combination or scavenging stops the chain). Example propagation in chlorination of methane: $CH_4 + Cl\cdot \rightarrow CH_3\cdot + HCl$ $CH_3\cdot + Cl_2 \rightarrow CH_3Cl + Cl\cdot$ The sum gives the net halogenation reaction.

🧪 Radical Halogenation: Reactivity and Selectivity

Reactivity of hydrogen types can be quantified experimentally; e.g., in butane 2° H react ~3.5× faster than 1° H. Chlorination has lower activation barriers and is less selective (more mixtures). Bromination is more selective because hydrogen abstraction is endothermic and thus favors formation of the most stable radical (higher $E_a$ selects for more stable radical formation).

⚖️ Thermodynamics and Kinetics

For radical hydrogen abstraction entropy changes are small, so $\Delta G \approx \Delta H$. Bond dissociation energies (BDEs) determine whether an abstraction is exothermic (favorable) or endothermic (unfavorable). Exothermic abstractions (e.g., Cl abstraction from weak C-H) proceed faster but are less selective; endothermic abstractions (e.g., Br) are slower but more selective.

➕ Polyhalogenation and Monohalogenation

With excess halogen radical, polyhalogenation occurs because halogenated products often have weaker C–H bonds and are more reactive toward further halogenation. To favor monohalogenation use limiting equivalents (1 eq) of halogen or conditions minimizing radical concentration.

🔁 Allylic Bromination and Role of NBS

Allylic bromination gives allylic radicals that are resonance-stabilized and can lead to multiple products. Molecular bromine can add across the double bond (ionic addition) as a competing pathway. N-Bromosuccinimide (NBS) is used to maintain low free $Br_2$ concentration by generating $Br\cdot$ slowly via reaction with trace $Br_2$ and $HBr$, favoring allylic radical formation and allylic bromination under light.

🧬 Autooxidation and Radical Scavengers

Autooxidation occurs when organic compounds react with molecular oxygen under mild conditions to give peroxides and hydroperoxides; volatile organic compounds (VOCs) are particularly susceptible. Radical scavengers / inhibitors (e.g., BHT, O2 in some contexts) stop chain reactions by reacting with radicals to form non-propagating species.

🔧 Grignard Reagents and Protecting Groups

Grignard reagents are organomagnesium halides with general formula $R!–!MgX$ and act like carbanions (strong bases; pKa of conjugate hydrocarbon >> 40). They are incompatible with weakly acidic or protic groups (OH, NH, COOH) and require protecting groups (commonly silyl ethers such as TMS or TBS) to prevent acid–base quenching. Prepare Grignards in aprotic, dry solvents and use excess reagent if an acid–base step is expected prior to nucleophilic addition.

🔗 Coupling Reactions (Gilman, Suzuki)

Gilman reagents (LiR) and organocuprates are used for carbon–carbon bond formation with alkyl halides. The Suzuki–Miyaura coupling uses organoboron reagents $R!–!B(OH)_2$ with a palladium catalyst to couple two carbon fragments; it's widely used because of mild conditions and tolerance of functional groups.

🔺 Oxidation States and Oxidation/Reduction

Assign carbon oxidation number roughly by counting bonds: each $C$–H counts as -1 (reducing for C), each $C$–X (X more electronegative than C) counts as +1 for carbon. Oxidation state changes track oxidation (loss of electrons / increase in oxidation number) and reduction (gain of electrons / decrease in oxidation number).

🌍 Environmental Impacts: CFCs, HFCs, HFAs

Chlorofluorocarbons (CFCs) are stable until high-energy UV causes halogen radical release that catalyzes ozone destruction. Hydrofluoroalkanes (HFAs/HFCs) replaced many CFCs because C–F bonds are strong; however HFAs are potent greenhouse gases and contribute to global warming.

✅ Summary and Practical Tips

• Remember the three radical steps: initiation, propagation, termination.
• Bromination = more selective; chlorination = faster but less selective.
• Use NBS for controlled allylic bromination; use silyl protecting groups for alcohols when making Grignard reagents.
• Track oxidation states by counting $C$–H and $C$–X bonds.

Study actively by drawing mechanisms for propagation and termination steps, predicting major products for monohalogenation, allylic bromination, and Grignard additions, and practicing oxidation-state calculations.