Detailed Study Notes – Reactions of Haloarenes (Metals, ESR, NSR, Dow’s Process)

Reactions With Metals (Organometallic Coupling)

• Haloarenes (Ar–X) can undergo metal‐mediated homocoupling/heterocoupling in dry ether.

Fittig Reaction

• $2\;\text{Ar–X}\; + \;2\;\text{Na}\;\xrightarrow[\text{dry ether}]{}\;\text{Ar–Ar}\; + \;2\;\text{NaX}$
• Produces biphenyl; useful for constructing bi-aryl frameworks.

Wurtz–Fittig Reaction

• Mixed coupling between an aryl and an alkyl halide.
• $\text{Ar–X}\; + \;\text{R–X}\; + \;2\;\text{Na}\;\xrightarrow[\text{dry ether}]{}\;\text{Ar–R}\; + \;2\;\text{NaX}$
• Gives alkyl-benzene (e.g.
– $\text{C}6\text{H}5\text{Cl}\; + \;\text{CH}3\text{Br}\; \to \;\text{C}6\text{H}5\text{CH}3$ + $\text{NaBr}$ ).

Formation & Basic Chemistry of Grignard Reagents

• Magnesium inserts into Ar–X bond in absolutely anhydrous ether.
• $\text{Ar–X}\; + \;\text{Mg}\; \xrightarrow[\text{dry ether}]{}\;\text{Ar–Mg–X}$ (phenyl magnesium halide).
• Highly nucleophilic/basic; reacts with even very weak acids (“Bakwas acid”) to regenerate benzene:
– $\text{Ar–Mg–X}\; + \;\text{ROH}\; \to \;\text{Ar–H}\; + \;\text{Mg(OR)X}$
• Synthetic sequence shown in transcript:

$\text{C}6\text{H}6 \xrightarrow[\text{AlCl}3]{\text{Cl}2}\; \text{C}6\text{H}5\text{Cl}$ (chlorination).
$\text{C}6\text{H}5\text{Cl} \xrightarrow[\text{ether}]{\text{Mg}} \; \text{C}6\text{H}5\text{MgCl}$ .
Hydrolysis with $\text{CH}_3\text{OH}$ gives benzene back.

Electrophilic Substitution Reactions (ESR) of Haloarenes

• Halogen (Cl, Br) is ortho/para-directing but overall deactivating.
– Reason: strong $-I$ (electron withdrawal) dominates over weak $+R$ (lone-pair donation).
– Para product generally predominates (steric relief + $-I\gg +R$ ).

Representative Reactions & Major Products

• Chlorination (second Cl): $\text{C}6\text{H}5\text{Cl}\; \xrightarrow[\text{AlCl}3]{\text{Cl}2}\; p\text{-dichlorobenzene}$ .
• Friedel–Crafts acylation: $\text{C}6\text{H}5\text{Cl}\; \xrightarrow[\text{AlCl}3]{\text{CH}3\text{COCl}}\; p\text{-chloroacetophenone}$ .
• Friedel–Crafts alkylation: $\text{Cl–C}6\text{H}5 \xrightarrow[\text{AlCl}3]{\text{CH}3\text{Cl}}\; p\text{-chlorotoluene (1-chloro-4-methylbenzene)}$ .
• Nitration: $\text{Conc.}\;\text{HNO}3/\text{H}2\text{SO}4$ → $p\text{-chloronitrobenzene}$ . • Sulfonation: $\text{Conc.}\;\text{H}2\text{SO}_4$ → $p\text{-chlorobenzenesulfonic\;acid}$ .

Nucleophilic Substitution Reactions (NSR) of Haloarenes

• Unactivated aryl halides are almost inert toward $\text{S}\text{N}1$ , $\text{S}\text{N}2$ & $\text{S}\text{N}!\text{Ar}$ under ordinary conditions.
– $\text{C}{sp^2}-X$ bond is short/strong. – Resonance gives partial $\pi$ character ("double-bond character"). – Phenyl cation (needed for $\text{S}\text{N}1$ ) is highly unstable.
– $\text{S}_\text{N}2$ backside is blocked by $\pi$ -electron cloud of ring.

Dow’s Process (Industrial Phenol)

• Drastic conditions force substitution.
• Step-1: $\text{C}6\text{H}5\text{Cl}\; + \;\text{NaOH}\; (623\,\text{K},\;300\,\text{atm})\; \to \;\text{C}6\text{H}5\text{ONa}$ .
• Step-2: Acidification $\xrightarrow{\text{H}^+}$ phenol $\,(\text{C}6\text{H}5\text{OH})$ .

Activation Toward $\text{S}\text{N}!\text{Ar}$ by Electron-Withdrawing Groups (EWG)

• Strong $-M/-I$ substituents (e.g. $\text{NO}2$ , $\text{CN}$ , $\text{SO}3H$ ) at ortho/para positions stabilize the Meisenheimer (σ-complex).
• Reactivity order shown in lecture (increasing):
\text{Cl–C}6\text{H}5 < o/p\text{-mono-NO}2 < o,p\text{-di-NO}2 \ll 2,4,6\text{-tri-NO}_2.

Typical Laboratory Conversions

$p\text{-nitrochlorobenzene}\; + \;\text{NaOH}\;(473\,\text{K}) \to p\text{-nitrophenol}$ .
2,4\text{-dinitrochlorobenzene} \xrightarrow[\text{Warm}]\text{NaOH} \to 2,4\text{-dinitrophenol}.
Successive nitration of phenol (or its salt) yields picric acid:
$\text{C}6\text{H}5\text{OH} \xrightarrow{3\,\text{HNO}3/\text{conc.}\,\text{H}2\text{SO}_4} 2,4,6\text{-trinitrophenol}$ .

Comparative Summary

• Halogens on benzene ring: meta-deactivators in terms of rate, yet ortho/para directors in orientation.
• Metal-mediated reactions (Fittig/Wurtz-Fittig) useful for C–C bond formation but demand strictly anhydrous conditions.
• Grignard reagents derived from haloarenes behave like those from haloalkanes but form more slowly because of stronger Ar–X bond.
• Electrophilic substitutions proceed more slowly than for benzene but give mainly para isomer.
• Nucleophilic substitution requires:
– High T/P (Dow’s).
– Or presence of strong EWGs to stabilize the anionic σ-complex.
• Understanding balance between electronic (–I, +R) and steric factors is essential for predicting product distribution and designing synthetic routes.