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Chapter 9. Radical Reactions

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1. Radical

2. Overview of Radical Reactions

3. Radical Substitution Reactions

4. Radical Addition Reactions

5. Radical Elimination Reactions

6. Other Radical Reactions

1. Radical

⑴ Definition: Intermediate with unpaired electrons

⑵ Stability of Radicals

① Stability: Phenyl Radical ＜ Vinyl Radical ＜ Methyl Radical ＜ 1° Radical ＜ 2° Radical ＜ 3° Radical ≪ Allyl Radical ＜ Benzyl Radical

② Higher carbon degree leads to higher stability (∵ sp3 → sp2 electron donating inductive effect)

③ Allyl and benzyl radicals are stabilized through resonance, making them stable

⑶ Formation

① Generated through thermal (Δ) or UV (hν) homolytic reactions

○ A-B → A · + · B

② Radical initiators: O-O, X-X have weak bond strength due to repulsion of non-bonding electron pairs, leading to radical formation

○ Examples: X₂, benzoyl peroxide, ROOR, AIBN, Ph(CO₂)₂

2. Overview of Radical Reactions

⑴ Overview

① Since outer electrons are not 8, radicals are electron-deficient and highly reactive

② Generally do not carry a charge

③ sp² hybridization

④ Unlike carbon cations, no rearrangement reactions occur

⑤ Propagation First Step is rate-determining step (r.d.s)

⑥ Radical reactions are categorized into radical substitution and radical addition reactions, distinguishable based on reaction conditions

⑵ Carbon Radical Rearrangement

① Carbon cations undergo rearrangement, but carbon radicals do not

② Explained by molecular orbital function

○ Assumption: Bonding orbital function A, antibonding orbital function B, C are given

○ In the case of carbon cation, both electrons fill A

○ In the case of carbon radical, 2 electrons fill A, and the remaining electron fills B or C

○ In carbon cation, 1s orbital and pi bonding have the same phase → rearrangement is possible

○ In carbon radical, 1s orbital and pi bonding have different phases → rearrangement is impossible

⑶ Conditions for Radical Substitution Reactions

① Condition 1: X₂ / hν or Δ

○ X₂ itself is a radical initiator, using separate ROOR is wasteful

② Condition 2: NBS / hν or ROOR: NBS / Δ condition can lead to undesirable reactions apart from radical generation

Figure 1. Structure of N-bromosuccinimide (NBS)

③ Condition 3: NBS + HBr / hν or ROOR

○ NBS reacts with HBr to produce Br₂

○ Br₂ is maintained at low concentration under this condition

Figure 2. Reaction between NBS and HBr

○ N-Br bond of NBS can be cleaved into N · + · Br bond, directly providing radicals

○ NBS is usually reacted under CCl4 solution conditions: NBS exists in solid state

⑷ Conditions for Radical Addition Reactions

① Condition 1: HBr / hν, Δ, or ROOR

② (Tip) If HBr is a sole reactant, it’s radical addition reaction; otherwise, it’s radical substitution reaction

③ However, NBS can also be used in radical addition reactions

3. Radical Substitution Reactions

⑴ Mechanism

① Overall reaction

Figure 3. Overview of Radical Substitution Reaction

② Initiation step

Figure 4. Initiation step

③ Propagation step

○ Reaction 1: Interaction with X · on sp³ carbon, rate-determining step

Figure 5. Propagation step 1

○ Reaction 2:

Figure 6. Propagation step 2

④ Termination step

○ Reaction 1: Cl · + · Cl → Cl₂

○ Reaction 2: CH₃CH₂ · + · CH₂CH₃ → CH₃CH₂-CH₂CH₃

○ Reaction 3: CH₃CH₂ · + · Cl → CH₃CH₂Cl

⑵ Site Selectivity

① Overview: Hydrogens with higher degree are more easily substituted due to radical stability in reaction mechanism

② Overall reaction equation

Figure 7. Overall reaction equation

③ F₂: Very reactive, undergoes multiple halogenation reactions

④ Cl₂: Highly reactive

○ Products: (CH₃)₃C-Cl (37%) + (CH₃)₂-CH-CH₂Cl (63%)

○ Highly reactive, multiple reactions can occur easily

○ Carbon radical intermediate step is exothermic ( ∵ Cl2 has high energy due to non-bonding electron pair repulsion)

○ Product ratio

○ 3° hydrogen substitution: 1° hydrogen substitution = 37: 63

○ Number ratio

○ 3° hydrogen: 1° hydrogen = 1: 9

○ Reactivity ratio

○ 3° hydrogen substitution: 1° hydrogen substitution = 37 (37 ÷ 1): 7 (63 ÷ 9)

⑤ Br₂: Highly selective

○ Products: (CH₃)₃C-Br (99%) + (CH₃)₂-CH-CH₂Br (1%)

○ Carbon radical intermediate step is endothermic: High activation energy leads to high selectivity

⑥ I₂: Very selective, but low reactivity so it’s hard to remove hydrogen radicals

⑦ Reactivity of F, Cl, Br radicals based on alkyl degree

Table. 1. Reactivity of F, Cl, Br radicals based on alkyl degree

⑧ Excess Halogen: Increases the ratio of multi-substituted halogenated alkane, decreasing the yield of single-substituted halogenated alkane.

⑨ Temperature Increase: Reverse reaction occurs actively, adjusting products; thermodynamically stable product becomes major product

⑩ Application 1. Chlorination of butane

○ Product ratio

○ 1-chlorobutane (30%) + 2-chlorobutation (70%)

○ Number ratio

○ primary hydrogen (60%) + secondary hydrogen (40%)

○ Reactivity ratio

○ primary hydrogen : secondary hydrogen = 30/6 : 70/4 = 1 : 3.5

⑶ Allylic Radical Substitution Reaction

① Allylic radical is more stable, so radical generated will be in the allylic position.

② Condition 1: X₂ / hν or Δ

○ Competes with alkene halogen addition reaction

○ Occurs well in high temperature, low concentration, non-polar solvent

○ Factor 1: High temperature: ΔS ＜ 0 in addition reaction, so ΔG increases with temperature increase in ΔG = ΔH - TΔS

○ Factor 2: Low concentration: In low concentration halogen addition reaction, probability of halonium ion formation and subsequent backside attack by halide is low

○ Factor 3: Non-polar solvent: If solvent can’t stabilize halonium ion, addition reaction rate slows down

③ Condition 2: NBS / hν or ROOR: Commonly used for allylic radical substitution reaction

④ Condition 3: NBS + HBr / hν or ROOR

○ Similar to condition 1, competes with alkene halogen addition reaction

○ However, Br₂ is maintained at low concentration in NBS + HBr, making radical substitution reaction more dominant

⑷ Benzyl Radical Substitution Reaction

① If benzyl radical is more stable, then radical generated will be in the benzyl position

② Condition 1: X₂ / hν or Δ: Possible

③ Condition 2: NBS / hν or ROOR: Possible

④ Condition 3: NBS + HBr / hν or ROOR: Possible

4. Radical Addition Reactions

⑴ Radical Addition Reactions of Alkenes

① Overall reaction

Figure 8. Overview of Radical Addition Reaction

② Initiation step

Figure 9. Initiation step

③ Propagation step

○ Reaction 1:

Figure 10. Propagation step 1

○ Reaction 2:

Figure 11. Propagation step 2

④ Termination step

○ Reaction 1: X · + X · → X₂

⑵ Radical Addition Reactions of Alkynes

① Reaction equation

Figure 12. Radical Addition Reaction of Alkynes

② In this reaction, Br moiety can resonate with radical carbon, making it a better electron-donating group than methyl group

○ In aromatic electrophilic addition reactions (EAS), halogen moiety is classified as EWG, but depends on reaction

⑶ Radical Addition Polymerization Reactions

5. Radical Elimination Reactions

⑴ Ozone Layer Depletion by Freon Gas (CFC)

⑵ Radical Inhibitors (Antioxidants)

① Types: Vitamin E, BHT (butylated hydroxy toluene)

② Substances that react with radicals instead

6. Other Radical Reactions

⑴ Cumene Process

① O₂ breaks into two O· radicals, each forms an OH group and reacts

② Tautomeric rearrangement can also occur

⑵ McLafferty Rearrangement

Figure 13. McLafferty Rearrangement

① Feature 1: Hydrogen radical migration

② Feature 2: Hexagonal ring transition state

③ Feature 3: Decomposes into neutral alkene and radical cation

Input: 2019.03.08 23:44