Reaction guide

Every key reaction drawn out — starting material, reagents over the arrow, product. Search by name or reagent, or filter by type. Part of the OChem study guide.

Markovnikov addition of H–X across C=C

Markovnikov addition of H–OH

Markovnikov alcohol, no rearrangement

Anti-Markovnikov, syn addition of H–OH

HalogenationAddition

Anti addition of two halogens (halonium ion)

Anti addition of X and OH

Anti-Markovnikov H–Br (radical)

Catalytic hydrogenationReduction

Syn addition of H–H → alkane

EpoxidationOxidation

Alkene → epoxide (syn)

Syn dihydroxylationOxidation

Adds two OH syn → cis diol

OzonolysisOxidation

Cleaves C=C into carbonyls

Markovnikov twice → geminal dihalide

Markovnikov → methyl ketone (via enol)

Anti-Markovnikov → aldehyde

Alkyne → cis (Z) alkene

Alkyne → trans (E) alkene

Extend the chain at a terminal alkyne

SN2 substitutionSubstitution

Backside attack, inversion

SN1 substitutionSubstitution

Via carbocation, racemization

E2 eliminationElimination

Anti-periplanar, one step, Zaitsev

E1 eliminationElimination

Via carbocation → Zaitsev alkene

Make OH a good leaving group

TosylationSubstitution

OH → tosylate (great leaving group)

E1 loss of water → alkene

1° alcohol → aldehyde (stops there)

1° alcohol → carboxylic acid

Anti opening → 1,2-diol

Aldehyde/ketone → alcohol

Even acids/esters → alcohol

Grignard additionOrganometallic

Adds R⁻ to a carbonyl (new C–C)

Stronger carbon nucleophile

Carbonyl → alkene

Protect a carbonyl as an acetal

Carbonyl + 1° amine → C=N imine

Carbonyl + 2° amine → enamine

Adds CN and OH across a carbonyl

Enolate + carbonyl → β-hydroxy carbonyl

Aldol + dehydration → enone/enal

Two esters → β-keto ester

Halogen on the α-carbon (via enol)

Acid + alcohol → ester (reversible)

Ester → carboxylate + alcohol

Acid chloride + amine → amide

Carbonyl + amine → amine

Puts a halogen on the ring (EAS)

NitrationAromatic

Installs –NO2 (EAS)

SulfonationAromatic

Installs –SO3H (reversible, EAS)

Adds an alkyl group (EAS)

Adds an acyl group (ketone)

Ar–NO2 → aniline

Brominates the allylic position

Substitutes an alkane C–H

Diels–AlderPericyclic

Concerted [4+2] → cyclohexene

Markovnikov HCl adds to the more subst. carbon

Markovnikov HI addition gives 2-iodoalkane

Anti DihydroxylationOxidation

Epoxide opened by water to a trans-1,2-diol

Cold Dilute KMnO4 DiolOxidation

Syn addition of two OH to give a cis-1,2-diol

Hot KMnO4 CleavageOxidation

Oxidative cleavage of alkene to carboxylic acids

Diol Cleavage (Periodic Acid)Oxidation

Cleaves a 1,2-diol into two carbonyl fragments

Simmons-Smith CyclopropanationAddition

Carbenoid adds CH2 across alkene to cyclopropane

Dichlorocarbene AdditionAddition

Dichlorocarbene adds to give dichlorocyclopropane

Alkene Cross MetathesisOrganometallic

Two terminal alkenes swap to an internal alkene

One HCl adds to terminal alkyne to a vinyl halide

Markovnikov HBr gives a 2-halo terminal alkene

Both pi bonds reduced fully to the alkane

Anti addition to a trans-1,2-dibromoalkene

Two Br2 add to give a tetrabromoalkane

Removes acidic sp C-H to form an acetylide

Acetylide + CarbonylOrganometallic

Acetylide adds to a carbonyl for propargyl alcohol

Kinetic 1,2-adduct across a conjugated diene

Thermodynamic 1,4-adduct across the diene

Diene + electron-poor dienophile to cyclohexene

Radical substitution at the allylic C-H position

Converts a primary or secondary alcohol into an alkyl chloride with retention/inversion; the leaving group departs as SO2 and HCl, avoiding carbocation rearrangements.

A primary alcohol is protonated, then bromide displaces water via SN2 to give the alkyl bromide.

A tertiary alcohol is protonated and loses water to form a stable 3deg carbocation, which is trapped by chloride via SN1.

A strong, non-nucleophilic base deprotonates the alcohol O-H to give the sodium alkoxide plus H2 gas.

An alkoxide acts as a nucleophile in an SN2 displacement on an unhindered alkyl halide to forge a new C-O bond, giving an ether.

A dialkyl ether is protonated then cleaved by iodide via SN2 (or SN1 for hindered cases), splitting the ether into an alkyl iodide and an alcohol.

Under basic conditions an alkoxide attacks the LESS hindered epoxide carbon via SN2, opening the ring to a beta-alkoxy alcohol.

Under acidic conditions the protonated epoxide is attacked at the MORE substituted carbon (more carbocation-like), giving a Markovnikov beta-methoxy alcohol.

A Grignard reagent adds a carbon nucleophile to the less hindered epoxide carbon, opening the ring and extending the chain to give a longer alcohol.

An amine nucleophile attacks the less hindered epoxide carbon, giving a beta-amino alcohol.

PCC is a mild oxidant that oxidizes a secondary alcohol to a ketone without over-oxidation.

A mild anhydrous oxidation converts a secondary alcohol to a ketone (or 1deg to aldehyde) via an alkoxysulfonium intermediate; no metal, no over-oxidation.

Vicinal Diol Cleavage (Periodic Acid)Oxidation

Periodic acid cleaves the C-C bond of a 1,2-diol via a cyclic periodate ester, giving two carbonyl compounds.

Pinacol RearrangementCarbonyl

A protonated 1,2-diol loses water to a carbocation, then a 1,2-alkyl shift and loss of a proton give a ketone (pinacolone).

A hydroxyl is capped as a trimethylsilyl ether to protect it during later steps; readily removed with fluoride.

An alcohol is converted to a methanesulfonate ester, turning a poor OH leaving group into an excellent one for later substitution or elimination.

Hydrosulfide (SH-) is a strong nucleophile that displaces halide via SN2 to give a thiol.

A thiolate nucleophile displaces halide via SN2 to form a thioether (sulfide).

Thiol Oxidation to DisulfideOxidation

Two thiols are oxidatively coupled at sulfur to form a disulfide bond, the linkage found in cystine.

Catalytic Hydrogenation of a KetoneReduction

Adds H2 across the carbonyl pi bond, reducing a ketone to a secondary alcohol.

Water adds reversibly to the carbonyl carbon to give a gem-diol; favored for small/electron-poor aldehydes.

One alcohol adds to the carbonyl to give a hemiacetal (an -OH and -OR on the same carbon).

Enol Ether FormationAddition

Acid-catalyzed condensation replaces the carbonyl O with =C-OR, giving a vinyl (enol) ether.

Hydroxylamine condenses with the carbonyl to give an oxime (C=N-OH).

Hydrazine condenses with the carbonyl to give a hydrazone (C=N-NH2).

Wolff-Kishner ReductionReduction

Deoxygenates a ketone all the way to a methylene (C=O to CH2) via the hydrazone under strong base.

Clemmensen ReductionReduction

Acidic-conditions deoxygenation of a ketone to a methylene (C=O to CH2).

1,2-Ethanedithiol adds twice to the carbonyl to give a cyclic dithiolane (thioacetal).

Raney Ni DesulfurizationReduction

Removes both sulfurs of a thioacetal, replacing the original C=O carbon with a CH2 (net deoxygenation).

Baeyer-Villiger OxidationOxidation

Inserts an oxygen next to the carbonyl, converting a ketone into an ester.

Aldehyde Oxidation to Carboxylic AcidOxidation

Oxidizes an aldehyde to the corresponding carboxylic acid.

Tollens Oxidation (Silver Mirror)Oxidation

Mild, selective oxidation of an aldehyde to a carboxylic acid, depositing metallic silver.

Exhaustively halogenates a methyl ketone alpha carbon then cleaves it to a carboxylate plus iodoform (CHI3).

The acetylide anion adds to the carbonyl carbon, giving a propargylic (alkynyl) alcohol.

alpha-Alkylation via EnolateCarbonyl

LDA forms the enolate, which is alkylated at the alpha carbon by an alkyl halide.

Conjugate (1,4) Addition of a CuprateOrganometallic

A cuprate adds 1,4 to an enone, installing an alkyl group at the beta carbon.

Conjugate Addition of an AmineAddition

An amine adds 1,4 (Michael addition) to an enone to give a beta-amino ketone.

Horner-Wadsworth-Emmons OlefinationCarbonyl

A stabilized phosphonate carbanion olefinates the aldehyde to give an E-alpha,beta-unsaturated ester.

Converts a carboxylic acid into a much more reactive acyl chloride, replacing OH with Cl; drives off SO2 and HCl gas.

Carboxylic Acid Reduction (LiAlH4)Reduction

Reduces a carboxylic acid all the way down to a primary alcohol; the strong hydride pushes past the acid to the CH2OH.

Condenses two carboxylic acids into an anhydride by loss of water, linking two acyl groups through one oxygen.

Water attacks the very reactive acyl chloride to regenerate the carboxylic acid, releasing HCl.

An alcohol displaces chloride from an acyl chloride to give an ester; fast and high-yielding versus Fischer esterification.

A carboxylate oxygen displaces chloride to build an anhydride; a mild route to mixed or symmetric anhydrides.

The mild cuprate delivers one alkyl group to an acyl chloride, stopping cleanly at the ketone without over-addition.

Aldehyde from Acyl Chloride (hindered hydride)Reduction

A bulky, mild hydride reduces an acyl chloride only to the aldehyde, avoiding further reduction to the alcohol.

Ammonia displaces the alkoxy group of an ester to give a primary amide plus an alcohol.

Two equivalents of Grignard add to an ester (through the ketone intermediate) to give a tertiary alcohol bearing two identical R groups.

Aldehyde from Ester (DIBAL-H)Reduction

One equivalent of DIBAL at low temperature reduces an ester only to the aldehyde via a stable tetrahedral intermediate.

Reduces an ester fully to a primary alcohol; the acyl carbon becomes CH2OH and the alkoxy group leaves as its own alcohol.

Swaps the alkoxy group of an ester for a new one from an added alcohol; an equilibrium driven by excess of the incoming alcohol.

Vigorous acid or base hydrolysis of the sturdy amide bond gives back the carboxylic acid (plus the amine/ammonia).

LiAlH4 reduces an amide to an amine, replacing the C=O with CH2 and keeping the C-N bond intact.

Full hydrolysis of a nitrile through the amide gives a carboxylic acid, adding one carbon relative to the starting halide.

Reduces a nitrile to a primary amine, adding two hydrogens across the C-N triple bond.

A Grignard adds once to a nitrile to give an imine salt that hydrolyzes on workup to a ketone.

Nitrile from Alkyl Halide (SN2)Substitution

Cyanide displaces a primary halide in an SN2 reaction, installing a nitrile and extending the carbon chain by one.

Decarboxylation of a Beta-Keto AcidElimination

A carboxylic acid beta to a carbonyl loses CO2 on heating through a cyclic six-membered transition state, giving a ketone.

Hell-Volhard-Zelinsky (alpha-bromination)Substitution

Brominates the alpha carbon of a carboxylic acid via its enol, giving an alpha-bromo acid useful for further substitution.

A bulky, strong, non-nucleophilic base removes the least hindered alpha-hydrogen to give the kinetic enolate irreversibly.

The carbonyl (keto) form interconverts with its enol via alpha-proton transfer; the keto form usually predominates at equilibrium.

Enolate alkylation (LDA then R-X)Carbonyl

The enolate carbon acts as a nucleophile in an SN2 attack on an alkyl halide, installing a new alpha-alkyl group.

A preformed enolate of one carbonyl adds to a second, different carbonyl to give a controlled beta-hydroxy carbonyl product.

An enolate attacks a carbonyl within the same molecule to close a ring, favoring five- and six-membered rings.

Dieckmann condensationCarbonyl

An intramolecular Claisen of a diester: one ester enolate attacks the other ester to form a cyclic beta-keto ester.

Malonic ester synthesisCarbonyl

Diethyl malonate is deprotonated, alkylated, then hydrolyzed and decarboxylated to give a substituted acetic acid.

Acetoacetic ester synthesisCarbonyl

Ethyl acetoacetate is alkylated at the alpha carbon, then hydrolyzed and decarboxylated to yield a substituted methyl ketone.

A stabilized enolate donor adds in conjugate fashion to the beta carbon of an enone to give a 1,5-dicarbonyl.

Stork enamine alkylationCarbonyl

A ketone is converted to an enamine that acts as a mild carbon nucleophile toward alkyl/acyl halides, then hydrolyzed back to the alpha-substituted ketone.

A Michael addition followed by an intramolecular aldol condensation builds a fused cyclohexenone ring.

Mannich reactionCarbonyl

An enol/enolate attacks an iminium ion (from an amine and formaldehyde) to install an aminomethyl group alpha to the carbonyl.

A carboxylic acid is brominated at its alpha carbon via the acyl bromide enol to give an alpha-bromo acid.

Electrophilic aromatic substitution installs a chlorine on the ring; AlCl3 polarizes Cl2 to generate the Cl+ electrophile.

Acylation adds a ketone (avoiding carbocation rearrangement), then reduction of the C=O gives a straight, unrearranged alkyl chain on the ring.

Clemmensen reduction of an aryl ketoneReduction

Reduces the carbonyl of an aryl ketone side chain all the way to a CH2, converting an acylbenzene into an alkylbenzene.

Wolff-Kishner reduction of an aryl ketoneReduction

Basic-conditions reduction of an aryl ketone carbonyl to a methylene, giving the alkylbenzene (acid-sensitive alternative to Clemmensen).

Benzylic oxidation of tolueneOxidation

Any benzylic C-H bearing carbon is oxidized down to a carboxylic acid; a methyl group on the ring becomes COOH.

Benzylic oxidation of ethylbenzeneOxidation

Oxidation cleaves the alkyl chain back to the benzylic carbon, converting any alkylbenzene with a benzylic H into benzoic acid.

Benzylic bromination (NBS)Radical

Radical bromination selective for the weak benzylic C-H bond, placing Br on the carbon next to the ring.

Side-chain chlorination of tolueneRadical

Under radical conditions (light) chlorine substitutes at the benzylic position rather than on the ring, giving benzyl chloride.

Nucleophilic aromatic substitution (SNAr)Substitution

A nitro group ortho/para to the leaving group stabilizes the Meisenheimer complex, letting hydroxide displace chloride on the ring.

SNAr with ammonia (nitro-activated)Substitution

Ammonia displaces the activated aryl chloride via addition-elimination, giving the nitro-substituted aniline.

Benzyne (elimination-addition)Substitution

A very strong base eliminates HX to form a benzyne triple bond, which is then attacked by the nucleophile to give an aniline.

Birch reductionReduction

Dissolving-metal reduction of the ring gives an unconjugated 1,4-cyclohexadiene, leaving two double bonds intact.

Catalytic hydrogenation of the ringReduction

Forcing conditions add hydrogen across all three formal double bonds, fully reducing the arene to a cyclohexane.

Diazonium salt formationSubstitution

A primary aryl amine is converted to a stable-at-cold aryl diazonium ion, the key branch point for many aromatic substitutions.

Sandmeyer chlorinationSubstitution

Copper(I) chloride replaces the diazonium group with chloride, installing a ring chlorine that EAS alone cannot place cleanly.

Sandmeyer brominationSubstitution

Copper(I) bromide swaps the diazonium group for bromide, giving the aryl bromide.

Sandmeyer cyanationSubstitution

Copper(I) cyanide replaces the diazonium group with a nitrile, adding a one-carbon handle to the ring.

Diazonium hydrolysis to phenolSubstitution

Warming the aryl diazonium ion in water substitutes the group with a hydroxyl, giving a phenol.

Diazonium reductive deaminationSubstitution

Replaces the diazonium group with hydrogen, letting an amino group be used as a temporary director and then removed.

Balz-Schiemann fluorinationSubstitution

The diazonium tetrafluoroborate decomposes thermally to install a fluorine, one of the few practical routes to aryl fluorides.

Gabriel SynthesisSubstitution

Phthalimide nitrogen alkylates an alkyl halide, then is cleaved to release a clean primary (1o) amine with no over-alkylation

Azide ion displaces a leaving group by SN2, then the alkyl azide is reduced to a primary (1o) amine

A nitrile is reduced to a primary amine, adding one carbon to the chain (CH2NH2)

Ammonia displaces a halide to give a primary amine; over-alkylation to 2o/3o/quaternary is a common caveat, so large excess NH3 is used

An amide carbonyl is reduced all the way to an amine (C=O removed, no oxygen retained)

Exhaustive methylation makes a quaternary ammonium hydroxide that eliminates on heating to give the LESS substituted (Hofmann) alkene

Cope EliminationElimination

A tertiary amine oxide undergoes a concerted syn elimination to give an alkene plus a hydroxylamine

A primary or secondary amine attacks an acyl chloride to form an amide; useful for protecting an amine

Anhydride acylates the amine nitrogen to give an acetamide, a common amine-protecting step

A primary amide is converted to a primary amine with LOSS of one carbon (via isocyanate), shortening the chain

An acyl azide loses N2 and rearranges to an isocyanate, which hydrolyzes to a primary amine (one carbon shorter)

A primary aromatic amine is converted to a diazonium salt, a versatile aryl electrophile for further substitution

An amine acts as a Bronsted base, accepting a proton to form a water-soluble ammonium salt

An aromatic nitro group is reduced to a primary aryl amine, a key aniline synthesis

A tertiary amine is oxidized at nitrogen to give an amine N-oxide

Repeated N-alkylation converts an amine into a quaternary ammonium salt with a permanent positive charge on nitrogen

A [4+2] cycloaddition of 1,3-butadiene with the electron-poor maleic anhydride dienophile forms a new six-membered ring bearing the fused anhydride.

The reverse [4+2]: on heating, cyclohexene fragments back into a diene and a dienophile, driven by entropy and loss of a stable small alkene.

Cope rearrangementPericyclic

A [3,3]-sigmatropic shift converting a 1,5-diene into an isomeric 1,5-diene through a concerted six-membered chair-like transition state.

Claisen rearrangementPericyclic

A [3,3]-sigmatropic rearrangement of an allyl vinyl ether that delivers a gamma,delta-unsaturated carbonyl compound.

A conjugated triene undergoes a disrotatory/conrotatory electrocyclization, forming one new sigma bond to give a cyclohexadiene ring.

Gilman cuprate + alkyl halideOrganometallic

A lithium dialkylcuprate couples with a primary alkyl halide, forging a new carbon-carbon bond to give an extended alkane.

Gilman cuprate + acyl chlorideOrganometallic

A Gilman reagent adds one alkyl group to an acyl chloride and stops at the ketone stage, unlike Grignard/organolithium reagents.

Suzuki couplingOrganometallic

A palladium-catalyzed cross-coupling of an aryl halide with an aryl boronic acid builds a biaryl carbon-carbon bond.

Heck reactionOrganometallic

A palladium-catalyzed coupling of an aryl halide with an alkene installs the aryl group on the alkene to give a substituted (usually trans) alkene.

Ozonolysis (oxidative workup)Oxidation

Ozone cleaves the carbon-carbon double bond; an oxidative H2O2 workup carries the fragments up to carboxylic acids.

Hot KMnO4 alkene cleavageOxidation

Hot, concentrated permanganate fully cleaves an alkene, oxidizing each carbon to a carboxylic acid (or ketone if fully substituted).

Hydrogenation of a nitrileReduction

Catalytic hydrogenation reduces a nitrile all the way to a primary amine by adding two equivalents of H2.

Hydrogenation of an alkyneReduction

With excess hydrogen and an active catalyst, an alkyne is fully reduced through the alkene to the corresponding alkane.

DIBAL reduction of a nitrileReduction

One equivalent of DIBAL-H partially reduces a nitrile to an imine intermediate that hydrolyzes on workup to an aldehyde.

Olefin metathesisOrganometallic

A ruthenium carbene scrambles alkene partners; two terminal alkenes exchange ends to give an internal alkene plus ethylene.

Corey-House synthesisOrganometallic

A lithium dialkylcuprate reacts with an alkyl halide to couple two alkyl fragments into a larger alkane with a new C-C bond.