Organic Chemistry Review: Key Reactions from 5.12 for 5.13

Comprehensive vocabulary flashcards detailing prerequisite organic reactions from 5.12 essential for 5.13, covering alkane, alkene, alkyne, functional group transformations, oxidations, reductions, and additions.

PCC Oxidation

• Starting materials: Primary or secondary alcohols

• Reagents: Pyridinium chlorochromate ($PCC$) in anhydrous dichloromethane ($CH_2Cl_2$)

• Products: Aldehydes (from $1^\circ$ alcohols) or ketones (from $2^\circ$ alcohols)

• Mechanism: Alcohol attacks the chromium center to form a chromate ester, followed by base-assisted elimination ($E2$-like) to generate the carbonyl group; absence of water prevents hydrate formation and stops over-oxidation to carboxylic acids.

Jones Oxidation

• Starting materials: Primary or secondary alcohols

• Reagents: Chromium trioxide or sodium dichromate in aqueous sulfuric acid and acetone ($CrO_3 / H_2SO_4 / H_2O$)

• Products: Carboxylic acids (from $1^\circ$ alcohols) or ketones (from $2^\circ$ alcohols)

• Mechanism: Formation of a chromate ester followed by elimination yields a carbonyl; in primary alcohols, aqueous conditions hydrate the aldehyde to a gem-diol, which undergoes a second chromate ester oxidation to form a carboxylic acid.

Bromination of Alcohols via Phosphorus Tribromide

• Starting materials: Primary or secondary alcohols

• Reagents: Phosphorus tribromide ($PBr_3$)

• Products: Alkyl bromides ($RBr$) and phosphorous acid ($H_3PO_3$)

• Mechanism: The alcohol hydroxyl oxygen attacks phosphorus, displacing a bromide ion to form a good leaving group ($-OPBr_2$); the displaced bromide ion then attacks the alkyl carbon in an $S_N2$ displacement with stereochemical inversion.

Acid Chloride Formation with Thionyl Chloride

• Starting materials: Carboxylic acids

• Reagents: Thionyl chloride ($SOCl_2$) and pyridine

• Products: Acyl chlorides ($RCOCl$), sulfur dioxide ($SO_2$), and pyridinium chloride

• Mechanism: The carboxylic acid attacks thionyl chloride to form a chlorosulfite intermediate; nucleophilic addition-elimination by chloride displaces the chlorosulfite, collapsing with the irreversible loss of $SO_2$ gas and chloride.

Reduction of Nitriles with Lithium Aluminum Hydride

• Starting materials: Nitriles ($RCN$)

• Reagents: Lithium aluminum hydride ($LiAlH_4$), followed by aqueous workup ($H_2O$)

• Products: Primary amines ($RCH_2NH_2$)

• Mechanism: Two consecutive nucleophilic hydride additions from aluminate to the electrophilic nitrile carbon form an imine aluminate intermediate and then an aluminum amide complex, which hydrolyzes upon aqueous workup to yield the primary amine.

Hydroboration-Oxidation of Alkenes

• Starting materials: Alkenes

• Reagents: 1. Borane ($BH_3\cdot THF$); 2. Alkaline hydrogen peroxide ($H_2O_2, NaOH$)

• Products: Primary or secondary alcohols (anti-Markovnikov regioselectivity, syn-stereospecificity)

• Mechanism: Concerted four-membered transition state delivers boron and hydrogen to the same double-bond face (syn), placing boron at the less substituted carbon; hydroperoxide anion coordinates boron, triggering alkyl migration with retention of configuration, followed by ester hydrolysis.

Lindlar Catalytic Hydrogenation

• Starting materials: Internal or terminal alkynes

• Reagents: Hydrogen gas ($H_2$ or $D_2$) over a poisoned palladium catalyst ($Pd / CaCO_3 / \text{quinoline}$)

• Products: $Z$ (cis) disubstituted alkenes (from internal alkynes) or monosubstituted alkenes (from terminal alkynes)

• Mechanism: Heterogeneous catalytic syn-addition of two hydrogen atoms to the same face of the alkyne; catalyst poisons suppress catalytic activity and prevent further hydrogenation to the alkane.

Metal-Ammonia (Dissolving-Metal) Reduction

• Starting materials: Internal alkynes

• Reagents: Sodium or lithium metal in liquid ammonia ($Na / NH_3(l)$ or $Li / NH_3(l)$)

• Products: $E$ (trans) disubstituted alkenes

• Mechanism: Single-electron transfer from solvated electrons forms a radical anion intermediate that equilibrates to the thermodynamically favored trans conformation to minimize electron repulsion; sequential protonation by ammonia, second electron transfer, and final protonation furnish the trans-alkene.

Wittig Reaction

• Starting materials: Aldehydes or ketones, and phosphonium ylides

• Reagents: Phosphonium ylide ($R_3P=CR'_2$)

• Products: Alkenes (mono-, di-, tri-, or tetrasubstituted) and triphenylphosphine oxide ($Ph_3P=O$)

• Mechanism: Nucleophilic [2+2] cycloaddition between the ylide carbon and carbonyl group yields a four-membered oxaphosphetane ring, which undergoes cycloreversion driven by the thermodynamic stability of the strong phosphorus-oxygen double bond ($P=O$).

E2 Elimination with Potassium tert-Butoxide

• Starting materials: Alkyl halides or alkyl sulfonates

• Reagents: Potassium tert-butoxide ($KO\text{-}t\text{-}Bu$)

• Products: Terminal alkenes, 1,1-disubstituted alkenes, or cyclic alkenes (Hofmann elimination products)

• Mechanism: Bimolecular elimination ($E2$) via a concerted anti-periplanar transition state; steric hindrance of the tert-butoxide base directs proton abstraction toward the least sterically hindered $\\beta$-hydrogen.

Propargylic Alcohol Synthesis

• Starting materials: Terminal alkynes and carbonyl compounds (formaldehyde, aldehydes, or ketones)

• Reagents: 1. Strong base (e.g., $n\text{-}BuLi$ or $NaNH_2$); 2. Formaldehyde, aldehyde, or ketone; 3. Mild aqueous acid workup ($H_3O^+$)

• Products: Primary, secondary, or tertiary propargylic alcohols

• Mechanism: Deprotonation of the terminal alkyne generates a nucleophilic metal acetylide; nucleophilic addition of the acetylide carbanion into the electrophilic carbonyl carbon affords an alkoxide, which protonates upon acidic workup.

Radical-Mediated Hydrobromination

• Starting materials: Terminal or unsymmetrical alkenes

• Reagents: Hydrogen bromide ($HBr$) and peroxides ($ROOR$) or light ($h\nu$)

• Products: Primary alkyl bromides (anti-Markovnikov addition)

• Mechanism: Free-radical chain mechanism: homolysis of peroxide generates alkoxy radicals that abstract hydrogen from $HBr$ to produce a bromine radical ($Br^\bullet$); addition of $Br^\bullet$ to the less substituted alkene carbon yields the more stable carbon radical, which abstracts hydrogen from $HBr$.

Electrophilic Aromatic Halogenation

• Starting materials: Arenes (aromatic rings)

• Reagents: Halogen ($Br_2$ or $Cl_2$) and Lewis acid catalyst ($FeBr_3$ or $FeCl_3$)

• Products: Aryl bromides or aryl chlorides, and hydrogen halide ($HX$)

• Mechanism: Electrophilic aromatic substitution ($S_EAr$): Lewis acid polarization of the halogen generates an active electrophile ($X^+$); nucleophilic attack by the aromatic $\\pi$-system generates a resonance-stabilized arenium ion (Wheland intermediate), followed by base-assisted proton removal to restore aromaticity.

Acid-Catalyzed Alkene Hydration

• Starting materials: Alkenes

• Reagents: Catalytic aqueous acid ($H_2SO_4 / H_2O$ or $H_3O^+$)

• Products: Secondary or tertiary alcohols (Markovnikov regioselectivity)

• Mechanism: Protonation of the alkene double bond forms the more stable carbocation intermediate; nucleophilic addition of water to the carbocation followed by proton transfer gives the alcohol.

Syn-Dihydroxylation of Alkenes

• Starting materials: Alkenes

• Reagents: Osmium tetroxide ($OsO_4$) with co-oxidant (e.g., $NMO$) or cold, alkaline potassium permanganate ($KMnO_4, NaOH$)

• Products: Cis-1,2-diols (syn-diols)

• Mechanism: Concerted [3+2] cycloaddition of the transition metal oxide across the alkene double bond places both oxygens simultaneously onto the same face, forming a cyclic osmate ester intermediate; subsequent hydrolysis yields the vicinal syn-diol.

Hydride Reduction of Carbonyls

• Starting materials: Aldehydes or ketones

• Reagents: Sodium borohydride ($NaBH_4$ in $MeOH$) or lithium aluminum hydride ($LiAlH_4$ in ether, followed by aqueous workup)

• Products: Primary alcohols (from aldehydes) or secondary alcohols (from ketones)

• Mechanism: Nucleophilic hydride transfer from the boron or aluminum reagent to the electrophilic carbonyl carbon forms an alkoxide-metal complex; protonation via protic solvent or aqueous acid workup furnishes the neutral alcohol.

Organometallic Addition to Esters

• Starting materials: Esters (or ethyl formate) and organolithium or Grignard reagents

• Reagents: 2 equivalents of $RLi$ or $RMgX$, followed by aqueous acid workup ($H_3O^+$)

• Products: Tertiary alcohols (from standard esters) or secondary alcohols (from ethyl formate, $HCO_2Et$)

• Mechanism: Nucleophilic addition of the first equivalent yields a tetrahedral intermediate that collapses by expelling the alkoxide leaving group to generate a ketone (or aldehyde); the resulting carbonyl undergoes rapid addition of a second equivalent of organometallic reagent to form an alkoxide, protonated upon workup.

Swern Oxidation

• Starting materials: Primary or secondary alcohols

• Reagents: Oxalyl chloride ($(COCl)_2$), dimethyl sulfoxide ($DMSO$), and triethylamine ($Et_3N$) in $CH_2Cl_2$

• Products: Aldehydes (from $1^\circ$ alcohols) or ketones (from $2^\circ$ alcohols), dimethyl sulfide ($Me_2S$), $CO$, and $CO_2$

• Mechanism: Reaction of $DMSO$ with oxalyl chloride generates chlorodimethylsulfonium; displacement by the alcohol oxygen yields an alkoxysulfonium ion; deprotonation by $Et_3N$ forms a sulfur ylide that collapses via an intramolecular 5-membered cyclic transition state to form the carbonyl.

Alkene Ozonolysis

• Starting materials: Alkenes

• Reagents: 1. Ozone ($O_3$); 2. Reductive workup (dimethyl sulfide, $Me_2S$, or zinc in acetic acid, $Zn / AcOH$)

• Products: Ketones (from disubstituted alkene carbons) and aldehydes (from monosubstituted alkene carbons)

• Mechanism: Concerted [3+2] cycloaddition of ozone across the alkene yields a primary ozonide (molozonide); retro-[3+2] cycloaddition and recombination give a stable secondary ozonide, which undergoes reductive cleavage to afford the carbonyl products.

Hydroboration-Oxidation of Terminal Alkynes

• Starting materials: Terminal alkynes

• Reagents: 1. Sterically hindered dialkylborane (e.g., $Sia_2BH$ or $9\text{-}BBN$); 2. Alkaline hydrogen peroxide ($H_2O_2, NaOH$)

• Products: Aldehydes

• Mechanism: Regioselective syn-addition of the bulky dialkylborane delivers boron exclusively to the terminal carbon to minimize steric clash; basic hydroperoxide oxidizes the alkenylborane with retention of configuration to an enol, which rapidly tautomerizes to the aldehyde.

Friedel-Crafts Acylation

• Starting materials: Arenes and acyl chlorides ($RCOCl$)

• Reagents: Lewis acid catalyst ($AlCl_3$ or $FeCl_3$)

• Products: Aryl ketones and $HCl$

• Mechanism: Electrophilic aromatic substitution ($S_EAr$): coordination of the acyl chloride to $AlCl_3$ leads to ionization forming a resonance-stabilized acylium ion ($RC\equiv O^+$); electrophilic attack by the aromatic ring produces an arenium ion intermediate, followed by deprotonation to restore aromaticity.

Acetal Synthesis

• Starting materials: Aldehydes or ketones, and alcohols (2 equivalents or 1 equivalent of a 1,2-diol)

• Reagents: Acid catalyst (e.g., tosylic acid, $TsOH$) with continuous removal of water

• Products: Acetals (or cyclic acetals) and water ($H_2O$)

• Mechanism: Acid-catalyzed nucleophilic addition of alcohol to the carbonyl affords a hemiacetal; protonation of the hydroxyl group and expulsion of water generates a resonance-stabilized oxocarbenium ion, which is attacked by a second alcohol molecule and deprotonated to give the acetal.

Imine Synthesis

• Starting materials: Aldehydes or ketones, and primary amines ($RNH_2$)

• Reagents: Acid catalyst with water removal

• Products: Imines ($R_2C=NR'$) and water ($H_2O$)

• Mechanism: Nucleophilic attack of the primary amine on the carbonyl carbon forms a tetrahedral carbinolamine intermediate; protonation of the hydroxyl group followed by dehydration yields an iminium ion, which loses a proton to establish the carbon-nitrogen double bond.

Alkene Epoxidation

• Starting materials: Alkenes

• Reagents: Peroxy acid (e.g., $mCPBA$ or $ArCO_3H$)

• Products: Epoxides (oxiranes) and carboxylic acid byproduct ($ArCO_2H$)

• Mechanism: Concerted