Reactions at Benzylic Positions, Aromatic Substitutions, and Carbonyl Synthesis

Vocabulary flashcards covering benzylic functionalization, reductions of benzene rings, electrophilic aromatic substitution (EAS), nucleophilic aromatic substitution (SNAr and benzyne), and alcohol/alkyne oxidations from Organic Chemistry Lectures 20-24.

N-Bromosuccinimide (NBS)

A reagent that provides a constant, low steady-state concentration of molecular bromine ($Br_2$) to promote radical allylic or benzylic bromination while minimizing competing ionic addition or electrophilic aromatic substitution reactions.

Chemoselective Hydrogenation of Arenes vs. Alkenes

The selective reduction of an alkene double bond over an aromatic ring using $H_2, Pd/C$ under mild conditions ($2\,\text{atm}$, $25\,^\circ\text{C}$), contrasted with complete aromatic ring reduction to cyclohexane requiring forcing conditions ($100\,\text{atm}$, $150\,^\circ\text{C}$).

$S_N2$ Reaction at the Benzylic Position

A bimolecular nucleophilic substitution where a primary benzyl halide (such as benzyl bromide) is displaced by a strong nucleophile (such as $NaOH$) to yield a primary benzylic alcohol.

$S_N1$ Reaction at the Benzylic Position

A unimolecular nucleophilic substitution where a substituted benzyl halide ionizes to form a resonance-stabilized benzylic carbocation intermediate before capture by a weak nucleophile (such as $H_2O$).

$E2$ Reaction of Benzylic Halides

A bimolecular elimination reaction where a sterically hindered strong base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) removes a $\beta$-hydrogen from a benzylic halide to form a conjugated aryl alkene.

$E1$ Dehydration of Benzylic Alcohols

An acid-catalyzed unimolecular elimination where heating a benzylic alcohol with concentrated sulfuric acid ($H_2SO_4$) promotes loss of water, producing a resonance-stabilized carbocation that is deprotonated to yield a conjugated alkene.

Birch Reduction with Electron-Donating Groups (EDG)

A dissolving-metal reduction of an alkylbenzene using sodium ($Na$), methanol ($CH_3OH$), and liquid ammonia ($NH_3$) that affords a non-conjugated 1,4-cyclohexadiene where the electron-donating alkyl substituent resides on an $sp^2$ carbon.

Birch Reduction with Electron-Withdrawing Groups (EWG)

A dissolving-metal reduction of an EWG-substituted benzene (such as an acylbenzene) using $Na$, $CH_3OH$, and liquid $NH_3$ that produces a 1,4-cyclohexadiene where the electron-withdrawing substituent resides on an $sp^3$ carbon.

Electrophilic Aromatic Substitution (EAS) Halogenation

The substitution of an aromatic hydrogen on benzene by a halogen using molecular bromine ($Br_2$) in the presence of a Lewis acid catalyst ($FeBr_3$ or $AlBr_3$) to yield bromobenzene.

Active Electrophile in EAS Halogenation

The activated Lewis acid-base complex ($Br-Br^+-AlBr_3^-$ or $Br-Br^+-FeBr_3^-$) that donates a bromonium-equivalent electrophile upon attack by the aromatic $\pi$ electrons.

EAS Sulfonation

The reversible electrophilic aromatic substitution of a benzene ring with fuming sulfuric acid (fuming $H_2SO_4$) to yield benzenesulfonic acid ($C_6H_5SO_3H$).

Active Electrophile in EAS Sulfonation

Sulfur trioxide ($SO_3$), a neutral electrophile possessing significant partial positive charge on the central sulfur atom due to polarized sulfur-oxygen double bonds.

EAS Nitration

The electrophilic aromatic substitution of benzene using a mixture of concentrated nitric acid ($HNO_3$) and concentrated sulfuric acid ($H_2SO_4$) to generate nitrobenzene.

Nitronium Ion ($NO_2^+$)

The linear active electrophile in EAS nitration generated through protonation and dehydration of nitric acid by sulfuric acid.

Friedel-Crafts Alkylation ($S_N2$-like Mechanism)

An EAS alkylation with a primary alkyl halide (such as chloroethane) and $AlCl_3$ or $FeCl_3$, wherein benzene directly attacks an activated Lewis acid complex ($CH_3CH_2-Cl^+-AlCl_3^-$) without forming a free primary carbocation.

Friedel-Crafts Alkylation ($S_N1$-like Mechanism)

An EAS alkylation with secondary or tertiary alkyl halides (such as 2-chlorobutane) in the presence of $AlCl_3$ or $FeCl_3$, proceeding via complete ionization to generate a discrete, solvated carbocation electrophile.

Friedel-Crafts Acylation

The electrophilic aromatic substitution reaction between benzene and an acyl chloride in the presence of $AlCl_3$ or $FeCl_3$ to yield an aryl ketone, avoiding polyalkylation and carbocation rearrangement.

Acylium Ion

A resonance-stabilized electrophilic intermediate ($R-\overset{+}{C}=O \rightleftharpoons R-C\equiv\overset{+}{O}$) generated by chloride abstraction from an acyl chloride by a Lewis acid catalyst during Friedel-Crafts acylation.

Reduction of Nitrobenzene to Aniline

A reduction protocol in which an aromatic nitro group ($-NO_2$) is converted to an primary amine ($-NH_2$) using $1)\text{ Fe or Sn, HCl}$ followed by neutralization with $2)\text{ NaOH}$.

Clemmensen Reduction

The deoxygenation of aryl ketones or aldehydes to methylene ($-CH_2-$) alkane groups using zinc amalgam ($Zn(Hg)$) and concentrated hydrochloric acid ($HCl$) with heat.

Exhaustive Benzylic Bromination

A free-radical halogenation where treatment of an alkylbenzene (such as toluene) with excess $N$-bromosuccinimide ($\text{NBS (xs)}$) and heat or light ($h\nu$) replaces all benzylic hydrogens with bromine to form a tribromomethyl group ($-CBr_3$).

Nucleophilic Aromatic Substitution ($S_NAr$)

A two-step addition-elimination pathway occurring on an aryl halide activated by an ortho- or para-electron-withdrawing group ($-NO_2$), where addition of a nucleophile ($NaOH$, heat) forms a Meisenheimer complex followed by departure of the halide leaving group.

Elimination-Addition (Benzyne Mechanism)

An aromatic substitution mechanism for unactivated aryl halides treated with an extremely strong base ($NaNH_2, NH_3$), proceeding via deprotonation and halide loss to form a reactive benzyne intermediate, followed by nucleophilic addition to yield regioisomeric aniline products.

Pyridinium Chlorochromate (PCC) Oxidation

A mild oxidation reagent used in dichloromethane ($CH_2Cl_2$) that oxidizes primary alcohols to aldehydes and secondary alcohols to ketones without over-oxidation to carboxylic acids.

Dess-Martin Periodinane (DMP) Oxidation

A hypervalent iodine reagent used in dichloromethane ($CH_2Cl_2$) to oxidize primary alcohols cleanly to aldehydes and secondary alcohols to ketones under mild conditions.

Swern Oxidation

A mild, non-metal-mediated oxidation process converting primary alcohols to aldehydes and secondary alcohols to ketones using dimethyl sulfoxide ($(CH_3)_2SO$), oxalyl chloride ($(COCl)_2$), and triethylamine ($Et_3N$).

Ozonolysis of Alkenes (Reductive Workup)

The cleavage of carbon-carbon double bonds using ozone ($O_3$) followed by dimethyl sulfide ($(CH_3)_2S$) to yield aldehydes and/or ketones.

Hydroboration-Oxidation of Alkynes

An anti-Markovnikov hydration involving borane ($BH_3$) followed by basic hydrogen peroxide ($H_2O_2, NaOH$) that converts terminal alkynes to aldehydes and internal alkynes to ketones via enol tautomerization.

Mercury-Catalyzed Hydration of Alkynes

A Markovnikov hydration of terminal alkynes using aqueous sulfuric acid ($H_2SO_4, H_2O$) and mercuric acetate ($Hg(OAc)_2$) to form methyl ketones via enol intermediates.

Jones Oxidation of Secondary Alcohols

An oxidation reaction that converts secondary alcohols to ketones using sodium dichromate in sulfuric acid ($Na_2Cr_2O_7, H_2SO_4, H_2O$) or chromium trioxide in aqueous acid and acetone ($CrO_3, H_3O^+, \text{Acetone}$).