Free Radical Reactions - SMILES & LaTeX Hybrid
Reference Template: E1cb Mechanism (SMILES + LaTeX Hybrid)
\( + \text{Base}^{\ominus} \rightleftharpoons \bigg[ \)
-->
\( \longleftrightarrow \)
\( \bigg] + \text{H-Base} \)
Visualized using: EWG = Acetyl (C=O), LG = Cl, R = Methyl. Stereo-chemistry mapping maintains proper structural representation.
SUMMARY
Types of Free Radical Reactions & Substitution Mechanism
[Subjective] Question 1: What is the mechanistic pathway of a free radical substitution reaction, such as the halogenation of methane?
- A) The reaction initiates with the homolytic cleavage of a halogen molecule in the presence of UV light or heat to form radicals. (Reaction 1:
Cl2 + hv → 2Cl•).
- B) The propagation phase involves the radical attacking the substrate to create an alkyl radical, which then reacts with another halogen molecule to propagate the chain. (Reaction 2:
Cl• + CH4 → CH3• + HCl) and (Reaction 3: CH3• + Cl2 → CH3-Cl + Cl•).
- C) The termination step occurs when two radicals combine, ending the chain reaction and forming side products. (Reaction 4:
Cl• + Cl• → Cl2) and (Reaction 5: CH3• + CH3• → CH3-CH3).
- D) All of the above.
Mechanism at an Aromatic Substrate & Directive Effects
[Subjective] Question 2: How do directive effects and chain-carrying agents influence free radical mechanisms at aromatic substrates?
- A) In gas-phase free radical reactions, steric repulsion is minimized; therefore, the directive nature of incoming electrophilic or nucleophilic radicals depends entirely on inductive and mesomeric effects.
- B) Because the mesomeric effect is identical at both ortho and para positions, the inductive effect acts as the deciding factor for the yield of the final product, except when very large substituents like a t-butyl group are present, which make steric factors the dominating force.
- C) For aromatic substrates, less toxic and highly reactive chain-carrying agents like
(Me3Si)3SiH (tris(trimethylsilyl)silane) are used to facilitate mechanisms such as disproportionation and proton abstraction.
- D) All of the above.
Reactivity at Bridgehead & Neighboring Group Assistance
[Subjective] Question 3: What governs the reactivity of aliphatic substrates, reactions at bridgehead carbons, and neighboring group assistance?
- A) Although 3° radicals are typically more stable, substitution can occur at highly strained bridgehead carbons; for example, Norbornane reacts with
SO2Cl2 / (PhCO2)2 to form 2-chloronorbornane.
- B) In neighboring group participation, an atom like bromine exerts a deactivating inductive effect due to its electronegativity, but it acts primarily as an activating factor because its lone pairs resonate with the formed radical, ultimately increasing the reaction rate.
- C) In aliphatic substrates, C-H bond abstraction is strictly governed by bond energies; the abstraction of hydrogen by a highly reactive chlorine radical from
CH3-CH3 is an exothermic process, making it highly favorable.
- D) All of the above.
Attacking Radicals Reactivity & The Effect of Solvents
[Subjective] Question 4: How does the specific halide radical and the choice of solvent affect reactivity and product selectivity?
- A) The reactivity of halide radicals decreases in the order of
F2 > Cl2 > Br2 > I2; F2 is so reactive it reacts in the dark, while I2 requires the presence of strong oxidizing agents like HNO3 or HIO4 to react.
- B) Usually, solvents do not play an important role in free radical reactions, keeping regioselectivity largely consistent across different aliphatic environments.
- C) A notable exception to the negligible solvent effect is observed when reacting an aliphatic chain with
Cl2/hv in benzene instead of hexane; the formation of a complex between the benzene ring and the chlorine radical drastically shifts product selectivity (e.g., favoring a 90% yield of a specific internal chloride instead of the usual 40%).
- D) All of the above.
Allylic Halogenation (NBS) & Oxidation of Aldehydes
[Subjective] Question 5: What are the mechanistic behaviors of NBS in allylic halogenation and the auto-oxidation of aldehydes?
- A) N-bromosuccinimide (NBS) is specifically used for allylic and benzylic bromination, as well as the \(\alpha\)-position of carbonyl carbons, by generating a continuous, low concentration of
Br2.
- B) The NBS mechanism involves the abstraction of an allylic hydrogen followed by reaction with HBr to generate bromine gas. (Reaction 1:
Br• + R-H → R• + HBr) and (Reaction 2: NBS + HBr → Succinimide + Br2).
- C) Aldehydes undergo oxidation to carboxylic acids using atmospheric
O2 via a free radical mechanism, where the intermediate formed is a peroxybenzoic acid which ultimately yields two moles of carboxylic acid. (Reaction 1: Ph-CHO + O2(hv) → Ph-C(=O)-O-OH).
- D) All of the above.
Auto-oxidation & Coupling of Alkynes
[Subjective] Question 6: What characterizes the auto-oxidation process and the free radical coupling of alkynes?
- A) Auto-oxidation is a very fast radical chain oxidation of molecules in the presence of atmospheric
O2, and it proceeds exceptionally fast whenever only one reactive hydrogen (like benzylic or allylic) is present in the substrate.
- B) Common real-world examples of auto-oxidation include the rancidity of oils (formation of hydroperoxides), the hardening of paints, and the commercial Cumene process for synthesizing phenol.
- C) The Eglinton reaction is the homo-coupling of terminal alkynes containing an acidic hydrogen; it utilizes a base (like pyridine) and
Cu(II) salts to generate an intermediate free radical, yielding a dialkyne product. (Reaction 1: R-C≡C-H + Cu(II)/pyridine → R-C≡C-C≡C-R) and (Reaction 2: R-C≡C(-) + Cu(II) → R-C≡C• + Cu(I)).
- D) All of the above.
Sandmeyer Reaction, Rearrangements, & Hunsdiecker Reaction
[Subjective] Question 7: Describe the mechanistic aspects of the Sandmeyer reaction, Free radical rearrangements, and the Hunsdiecker reaction.
- A) The Sandmeyer reaction involves the halogenation or cyanation of an aromatic ring using diazonium salts and cuprous halides. (Reaction 1:
Ar-N2(+)X(-) + CuX → Ar-X + N2 + CuX2).
- B) Free radicals can undergo rearrangement to obtain stability and yield more stable products; the migratory ability for groups shifting to stabilize the radical strictly follows the order
H > Ph > CH3.
- C) The Hunsdiecker reaction uses silver salts of carboxylic acids to form alkyl bromides but strictly fails for aromatic substrates due to competing aromatic electrophilic substitution. (Reaction 1:
R-COOAg + Br2 + Δ → R-Br + AgBr + CO2).
- D) All of the above.
DETAILED
In this detailed section, the textual reaction equations have been fully integrated visually using the inline SMILES and MathJax Flexbox layout.
Types of Free Radical Reactions & Substitution Mechanism
[Subjective] Question 1: What is the mechanistic pathway of a free radical substitution reaction, such as the halogenation of methane?
- A) The reaction initiates with the homolytic cleavage of a halogen molecule in the presence of UV light or heat to form radicals.
\( \xrightarrow{h\nu \text{ or } \Delta} 2 \times \)
\( \text{Cl}^\bullet \)
- B) The propagation phase involves the radical attacking the substrate to create an alkyl radical, which then reacts with another halogen molecule to propagate the chain.
\( \text{Cl}^\bullet + \)
\( \longrightarrow \)
\( ^\bullet + \text{HCl} \)
\( ^\bullet + \)
\( \longrightarrow \)
\( + \text{Cl}^\bullet \)
- C) The termination step occurs when two radicals combine, ending the chain reaction and forming side products.
\( \text{Cl}^\bullet + \text{Cl}^\bullet \longrightarrow \)
\( ^\bullet + \)
\( ^\bullet \longrightarrow \)
- D) All of the above.
Mechanism at an Aromatic Substrate & Directive Effects
[Subjective] Question 2: How do directive effects and chain-carrying agents influence free radical mechanisms at aromatic substrates?
- A) In gas-phase free radical reactions, steric repulsion is minimized; therefore, the directive nature of incoming electrophilic or nucleophilic radicals depends entirely on inductive and mesomeric effects.
- B) Because the mesomeric effect is identical at both ortho and para positions, the inductive effect acts as the deciding factor for the yield of the final product, except when very large substituents like a t-butyl group are present, which make steric factors the dominating force.
- C) For aromatic substrates, less toxic and highly reactive chain-carrying agents like
(Me3Si)3SiH (tris(trimethylsilyl)silane) are used to facilitate mechanisms such as disproportionation and proton abstraction.
\( \text{Structure of } (\text{Me}_3\text{Si})_3\text{SiH}: \)
- D) All of the above.
Reactivity at Bridgehead & Neighboring Group Assistance
[Subjective] Question 3: What governs the reactivity of aliphatic substrates, reactions at bridgehead carbons, and neighboring group assistance?
- A) Although 3° radicals are typically more stable, substitution can occur at highly strained bridgehead carbons; for example, Norbornane reacts with
SO2Cl2 / (PhCO2)2 to form 2-chloronorbornane.
\( + \)
\( \xrightarrow{(\text{PhCO}_2)_2} \)
- B) In neighboring group participation, an atom like bromine exerts a deactivating inductive effect due to its electronegativity, but it acts primarily as an activating factor because its lone pairs resonate with the formed radical, ultimately increasing the reaction rate.
- C) In aliphatic substrates, C-H bond abstraction is strictly governed by bond energies; the abstraction of hydrogen by a highly reactive chlorine radical from
CH3-CH3 is an exothermic process, making it highly favorable.
- D) All of the above.
Attacking Radicals Reactivity & The Effect of Solvents
[Subjective] Question 4: How does the specific halide radical and the choice of solvent affect reactivity and product selectivity?
- A) The reactivity of halide radicals decreases in the order of
F2 > Cl2 > Br2 > I2; F2 is so reactive it reacts in the dark, while I2 requires the presence of strong oxidizing agents like HNO3 or HIO4 to react.
- B) Usually, solvents do not play an important role in free radical reactions, keeping regioselectivity largely consistent across different aliphatic environments.
- C) A notable exception to the negligible solvent effect is observed when reacting an aliphatic chain with
Cl2/hv in benzene instead of hexane; the formation of a complex between the benzene ring and the chlorine radical drastically shifts product selectivity.
\( \text{Benzene-Chlorine Complex:} \)
\( \cdots \text{Cl}^\bullet \)
- D) All of the above.
Allylic Halogenation (NBS) & Oxidation of Aldehydes
[Subjective] Question 5: What are the mechanistic behaviors of NBS in allylic halogenation and the auto-oxidation of aldehydes?
- A) N-bromosuccinimide (NBS) is specifically used for allylic and benzylic bromination, as well as the \(\alpha\)-position of carbonyl carbons, by generating a continuous, low concentration of
Br2.
- B) The NBS mechanism involves the abstraction of an allylic hydrogen followed by reaction with HBr to generate bromine gas.
\( \text{Br}^\bullet + \)
\( \longrightarrow \)
\( ^\bullet + \text{HBr} \)
\( + \text{HBr} \longrightarrow \)
\( + \text{Br}_2 \)
- C) Aldehydes undergo oxidation to carboxylic acids using atmospheric
O2 via a free radical mechanism, where the intermediate formed is a peroxybenzoic acid which ultimately yields two moles of carboxylic acid.
\( \xrightarrow{\text{O}_2(h\nu)} \)
- D) All of the above.
Auto-oxidation & Coupling of Alkynes
[Subjective] Question 6: What characterizes the auto-oxidation process and the free radical coupling of alkynes?
- A) Auto-oxidation is a very fast radical chain oxidation of molecules in the presence of atmospheric
O2, and it proceeds exceptionally fast whenever only one reactive hydrogen (like benzylic or allylic) is present in the substrate.
- B) Common real-world examples of auto-oxidation include the rancidity of oils (formation of hydroperoxides), the hardening of paints, and the commercial Cumene process for synthesizing phenol.
- C) The Eglinton reaction is the homo-coupling of terminal alkynes containing an acidic hydrogen; it utilizes a base (like pyridine) and
Cu(II) salts to generate an intermediate free radical, yielding a dialkyne product.
\( 2 \times \)
\( \xrightarrow{\text{Cu(II) / pyridine}} \)
\( + \text{Cu(II)} \longrightarrow \)
\( ^\bullet + \text{Cu(I)} \)
- D) All of the above.
Sandmeyer Reaction, Rearrangements, & Hunsdiecker Reaction
[Subjective] Question 7: Describe the mechanistic aspects of the Sandmeyer reaction, Free radical rearrangements, and the Hunsdiecker reaction.
- A) The Sandmeyer reaction involves the halogenation or cyanation of an aromatic ring using diazonium salts and cuprous halides.
\( + \text{CuCl} \longrightarrow \)
\( + \text{N}_2 \uparrow + \text{CuCl}_2 \)
- B) Free radicals can undergo rearrangement to obtain stability and yield more stable products; the migratory ability for groups shifting to stabilize the radical strictly follows the order
H > Ph > CH3.
- C) The Hunsdiecker reaction uses silver salts of carboxylic acids to form alkyl bromides but strictly fails for aromatic substrates due to competing aromatic electrophilic substitution.
\( + \text{Br}_2 \xrightarrow{\Delta} \)
\( + \text{AgBr} \downarrow + \text{CO}_2 \uparrow \)
- D) All of the above.
