Key Mechanisms and Reactions for Organic Chemistry Exam 1 (Chapters 12–14)

Electrophilic Aromatic Substitution (EAS)

Overview of EAS

Electrophilic Aromatic Substitution is a fundamental reaction type in aromatic chemistry, where an aromatic ring reacts with an electrophile, resulting in the substitution of a hydrogen atom. This mechanism preserves the aromaticity of the ring.

• Step 1: Generation of the Electrophile – The electrophile is produced, often with the help of a catalyst.

• Step 2: Formation of the Arenium Ion – The aromatic ring attacks the electrophile, forming a resonance-stabilized carbocation (arenium ion).

• Step 3: Deprotonation – Loss of a proton restores aromaticity.

General Equation:

$\ce{Ar-H + E^+ \rightarrow Ar-E + H^+}$

Example: Bromination of benzene using Br2 and FeBr3 as a catalyst.

Specific EAS Reactions

Bromination, Chlorination, Nitration, Sulfonation, Friedel–Crafts Alkylation & Acylation

• Bromination/Chlorination: Introduction of Br or Cl to the aromatic ring using Br2/Cl2 and a Lewis acid (FeBr3/FeCl3).

• Nitration: Introduction of a nitro group using HNO3 and H2SO4.

• Sulfonation: Introduction of a sulfonic acid group using fuming H2SO4 (SO3 in H2SO4).

• Friedel–Crafts Alkylation: Introduction of an alkyl group using an alkyl halide and AlCl3.

• Friedel–Crafts Acylation: Introduction of an acyl group using an acyl chloride and AlCl3.

Example Equation (Nitration):

$\ce{C6H6 + HNO3 \xrightarrow{H2SO4} C6H5NO2 + H2O}$

Activators and Deactivators in Aromatic Substitution

Effect on Reactivity and Orientation

Substituents on the aromatic ring influence both the rate and the position of further substitution. Activators increase reactivity and direct new substituents to the ortho/para positions, while deactivators decrease reactivity and often direct to the meta position.

• Activators: Electron-donating groups (e.g., –OH, –OCH3, –NH2).

• Deactivators: Electron-withdrawing groups (e.g., –NO2, –CF3, –COOH).

• Resonance Structures: Drawing resonance structures helps explain the directing effects and stabilization/destabilization of intermediates.

Example: The –OH group activates the ring and directs substitution to ortho and para positions.

Arenediazonium Salts

Formation and Reactions

Arenediazonium salts are formed by the reaction of aromatic amines with nitrous acid (generated in situ from NaNO2 and HCl). These salts are versatile intermediates for introducing various substituents onto aromatic rings.

• Formation: $\ce{ArNH2 + HNO2 + HCl \rightarrow ArN2^+Cl^- + 2H2O}$

• Reactions: Sandmeyer reactions (replacement with Cl, Br, CN), Schiemann reaction (replacement with F), and coupling reactions with phenols or aromatic amines.

Example: Conversion of aniline to chlorobenzene via diazonium salt intermediate.

Nucleophilic Aromatic Substitution (NAS)

Mechanism and Requirements

Nucleophilic Aromatic Substitution occurs when a nucleophile replaces a leaving group (often a halide) on an aromatic ring, typically facilitated by electron-withdrawing groups ortho or para to the leaving group.

• Addition–Elimination (SNAr) Mechanism: Involves formation of a Meisenheimer complex intermediate.

• Benzyne Mechanism: Involves elimination to form a benzyne intermediate, followed by nucleophilic addition (not required in detail for this exam).

Example: Conversion of p-nitrochlorobenzene to p-nitrophenol using NaOH.

Diels–Alder Reaction

Cycloaddition Mechanism

The Diels–Alder reaction is a [4+2] cycloaddition between a conjugated diene and a dienophile, forming a six-membered ring. It is a concerted, stereospecific reaction.

• Requirements: Diene must be in s-cis conformation; dienophile is often electron-deficient.

• Product Stereochemistry: Stereochemistry of reactants is preserved in the product.

General Equation:

$\ce{Diene + Dienophile \rightarrow Cyclohexene~derivative}$

Example: 1,3-butadiene reacts with ethene to form cyclohexene.

Syn Dihydroxylation of Alkenes (OsO4)

Mechanism and Application

Syn dihydroxylation introduces two hydroxyl groups to the same side (syn addition) of an alkene, typically using osmium tetroxide (OsO4).

• Reagents: OsO4 (catalytic), often with a co-oxidant like NMO or H2O2.

• Product: Vicinal (neighboring) diol with syn stereochemistry.

Equation:

$\ce{RCH=CHR' + OsO4 + H2O2 \rightarrow RCH(OH)-CH(OH)R'}$

Example: Cyclohexene to cis-1,2-cyclohexanediol.

Wittig Reaction

Alkene Synthesis via Ylides

The Wittig reaction forms alkenes by reacting aldehydes or ketones with phosphonium ylides.

• Ylide Formation: Triphenylphosphine reacts with an alkyl halide, then deprotonated by a strong base.

• Reaction: Ylide reacts with carbonyl compound to form a new C=C bond.

General Equation:

$\ce{R2C=O + Ph3P=CHR' \rightarrow R2C=CHR' + Ph3P=O}$

Example: Benzaldehyde reacts with methyltriphenylphosphonium ylide to give styrene.

Formation and Reaction of Acetylide Ions

Alkyne Chemistry

Acetylide ions are strong nucleophiles formed by deprotonating terminal alkynes with a strong base. They are useful for carbon–carbon bond formation.

• Formation: Terminal alkyne + strong base (e.g., NaNH2) yields acetylide ion.

• Reactions: Acetylide ions react with primary alkyl halides in SN2 reactions to extend carbon chains.

Equation:

$\ce{RC#CH + NaNH2 \rightarrow RC#C^-Na^+ + NH3}$

$\ce{RC#C^- + R'CH2X \rightarrow RC#CCH2R' + X^-}$

Example: Propyne reacts with NaNH2 to form propynyl anion, which then reacts with methyl iodide to give 1-butyne.

Additional info: This guide summarizes the most important mechanisms and reactions from Chapters 12–14 for exam preparation. Other mechanisms (e.g., Clemmensen reduction, side-chain oxidation, benzyne reaction) are not required in detail for this exam.