Organic Chemistry 1 · Reasoning about reactions
Substitution pathways: practice problems
234 problems, each with its worked solution. Open one to read every step, or filter by tag.
Start drawing: Substitution pathways
Tap one to draw it yourself with every arrow checked, or watch the steps. No sign-up.
- 1-bromobutane from butan-1-ol and HBr
- tert-Butyl bromide hydrolysis
- Displace bromide at methyl carbon
- Follow an ionization-and-capture branch
- Extend the chain with cyanide
- Finkelstein reaction — iodide exchange in acetone
- Preserve an adjacent double bond
- Make an ester without attacking an acyl carbon
- Close a sulfur-containing ring
Draw the mechanism 200
- Displace bromide at methyl carbonDraw simultaneous nucleophile attack and leaving-group departure in SN2.
- Follow an ionization-and-capture branchRetain charges and spectator ions throughout an SN1 alcohol-forming branch.
- Extend the chain with cyanideUse the carbon end of an ambident nucleophile and retain the nitrile triple bond.
- Finkelstein reaction — iodide exchange in acetoneDistinguish a nucleophilic halide from the departing halide while conserving both ions.
- Preserve an adjacent double bondApply sulfur nucleophilicity to direct allylic SN2 rather than adding to the unactivated alkene.
- Make an ester without attacking an acyl carbonDistinguish carboxylate O-alkylation at sp3 carbon from nucleophilic acyl substitution.
- Close a sulfur-containing ringIdentify an intramolecular SN2 pair source and count the ring atoms rather than adding a second molecule.
- Follow a neutral oxygen nucleophileDistinguish the oxonium product of neutral-nucleophile SN2 from the neutral ether after deprotonation.
- SN2 substitution — 2-bromobutane and hydroxideDraw a backside attack and see how it flips the arrangement around carbon.
- SN1 substitution — a 1,2-hydride shift on the wayDraw bromide leaving, a hydride shift, water attack and proton loss to make the rearranged alcohol.
- Follow the other end of an allylic ionDistinguish resonance redistribution from rearrangement while forming a transposed substitution product.
- Alkylate a neutral sulfideRecognize a stable cationic substitution product with no proton available for neutralizing deprotonation.
- Solvolysis with a methyl shiftCarry a secondary cation next to a quaternary carbon through a 1,2-methyl shift, methanol capture and proton transfer to solvent.
- Lose a configuration through a planar cationExplain why an SN1 reaction of one enantiomer gives both enantiomers of the product by following the planar carbocation.
- Join an alkoxide to a primary bromideBuild an unsymmetrical ether by alkoxide SN2 at a primary carbon and explain why the unhindered bromide favors substitution over elimination.
- Install nitrogen with azideChoose a terminal azide nitrogen as the SN2 nucleophile and assign formal charges across the N=N⁺=N⁻ unit of the alkyl azide.
- Make a thioether with a sulfur anionRelate thiolate size, polarizability and weak basicity to clean SN2 formation of a dialkyl sulfide.
- Methylate ammonia and free the amineSeparate the ammonium ion formed when neutral nitrogen does SN2 from the neutral amine released by a second ammonia, and explain why excess ammonia limits overalkylation.
- Turn a primary OH into a leaving groupConvert a primary alcohol to an alkyl bromide by protonating OH into a water leaving group, then displacing water by backside SN2 without forming a primary carbocation.
- Convert a tertiary alcohol through its cationSequence OH protonation, loss of water to a tertiary carbocation, and bromide capture as three separate SN1 events on a ring alcohol.
- Couple two alcohols into an etherMake a symmetrical ether from a primary alcohol by using one alcohol molecule as the nucleophile and a protonated one as the electrophile.
- Displace a sulfonate leaving groupTreat a sulfonate ester as an alkyl halide equivalent whose resonance-stabilized anion leaves during carbon SN2.
- Invert a secondary alcohol with PBr₃Use oxygen attack on PBr₃ to make a leaving group without carbocation formation, then predict inversion at the alcohol carbon from the bromide backside attack.
- Close an epoxide from the back sideExplain why a trans cyclic halohydrin closes to an epoxide: the alkoxide must reach the C–Cl carbon from the face opposite chlorine, as in any SN2.
- Alkylate phosphorus to make a phosphonium saltUse phosphorus as a neutral, highly polarizable SN2 nucleophile and assign the charge of the phosphonium salt that precedes a Wittig reagent.
- Ionize a primary benzylic bromideExplain why a primary benzylic halide can ionize in water, then complete water capture and deprotonation to the alcohol.
- Deprotonate, then close a six-membered etherGenerate an alkoxide irreversibly with hydride and close a six-membered cyclic ether by intramolecular SN2 at the tethered primary carbon.
- Replace OH with Cl using thionyl chlorideActivate a primary alcohol at sulfur with SOCl₂, then replace the C–O bond by chloride SN2 while the leaving group fragments to SO₂ gas.
- SN1 ethanolysis of tert-butyl bromideDraw the SN1 solvolysis of tert-butyl bromide in ethanol: ionisation to the carbocation, capture by ethanol, and deprotonation of the oxonium ion by ethanol.
- Azide displaces tosylate from cyclohexyl tosylateDraw the one-step SN2 attack of azide on cyclohexyl tosylate that expels the tosylate anion and gives azidocyclohexane.
- Cyanide displaces bromide from (1-bromoethyl)benzeneDraw the one-step SN2 displacement of bromide from (1-bromoethyl)benzene by cyanide, giving 2-phenylpropanenitrile.
- Methanethiolate displaces chloride from benzyl chlorideDraw the single SN2 step in which methanethiolate attacks benzyl chloride and chloride leaves, giving benzyl methyl sulfide.
- Acid-catalysed methanol opening of 2,2-dimethyloxiraneDraw protonation of 2,2-dimethyloxirane, methanol attack at the tertiary carbon, and deprotonation to 2-methoxy-2-methylpropan-1-ol.
- Acid-catalysed hydrolysis of ethylene oxideDraw protonation of the ethylene oxide oxygen, backside attack of water on a ring carbon, and deprotonation of the oxonium ion to ethylene glycol.
- meso-Butane-2,3-diol from trans-2,3-dimethyloxiraneDraw protonation of trans-2,3-dimethyloxirane, backside attack of water with inversion, and deprotonation to meso-butane-2,3-diol.
- Thioanisole from tetramethylammonium and thiophenolateDraw thiophenolate displacing trimethylamine from the tetramethylammonium ion to give thioanisole.
- Trimethylanilinium iodide from N,N-dimethylaniline and MeIDraw the SN2 quaternization of N,N-dimethylaniline by iodomethane that gives N,N,N-trimethylanilinium iodide.
- Diethyl benzylphosphonate by the Michaelis–Arbuzov reactionDraw the two SN2 steps of the Michaelis–Arbuzov reaction that turn triethyl phosphite and benzyl bromide into diethyl benzylphosphonate.
- Aziridine closure from 2-chloroethylamineDraw the intramolecular SN2 of 2-chloroethylamine to the aziridinium ion and the deprotonation by hydroxide that gives aziridine.
- Methyloxirane from 1-chloropropan-2-ol and NaOHDraw deprotonation of 1-chloropropan-2-ol by hydroxide and the intramolecular backside attack of the alkoxide that closes methyloxirane.
- Styrene oxide from 2-bromo-1-phenylethanolDraw deprotonation of the benzylic alcohol of 2-bromo-1-phenylethanol and alkoxide displacement of bromide to give styrene oxide.
- Cyclopentene oxide from trans-2-bromocyclopentanolDraw deprotonation of trans-2-bromocyclopentanol and the anti backside closure of the alkoxide onto the C–Br carbon to give cyclopentene oxide.
- 1-bromobutane from butan-1-ol and HBrDraw the protonation of butan-1-ol by HBr and the SN2 displacement of water by bromide that gives 1-bromobutane.
- HBr on (S)-1-phenylethanol gives racemic bromideDraw the SN1 mechanism by which concentrated HBr converts (S)-1-phenylethanol into racemic (1-bromoethyl)benzene through a benzylic cation.
- HBr on (S)-2-methylbutan-1-ol keeps the stereocenterDraw protonation and SN2 displacement that convert (S)-2-methylbutan-1-ol into (S)-1-bromo-2-methylbutane, and explain why the stereocenter is unchanged.
- HBr on (R)-3-methylhexan-3-ol gives racemic bromideDraw the SN1 mechanism by which HBr converts (R)-3-methylhexan-3-ol into racemic 3-bromo-3-methylhexane.
- tert-Butanol + HBrDraw protonation of tert-butyl alcohol by HBr, loss of water to the tert-butyl cation, and capture of the cation by bromide (substrate: tert-butanol with concentrated HBr).
- Lucas reagent on (R)-butan-2-ol gives racemic chlorideDraw the Lucas-reagent mechanism in which ZnCl2 activates (R)-butan-2-ol, the sec-butyl cation forms, and chloride gives racemic 2-chlorobutane.
- 1-iodopropane from propan-1-ol and HIDraw the protonation of propan-1-ol by HI and the SN2 displacement of water by iodide that gives 1-iodopropane.
- N,N-Dimethylpyrrolidinium by intramolecular MenshutkinDraw the 5-exo-tet ring closure in which the dimethylamino nitrogen of 4-chloro-N,N-dimethylbutan-1-amine displaces chloride.
- S-Benzylisothiouronium bromide from thioureaDraw thiourea attacking benzyl bromide through sulfur and the resonance that delocalizes the charge in S-benzylisothiouronium bromide.
- DABCO mono-quaternization with benzyl chlorideDraw one DABCO nitrogen attacking benzyl chloride by SN2 to give the mono-benzylated DABCO chloride salt.
- N,N-Dimethylpiperidinium iodide from N-methylpiperidineDraw the Menshutkin SN2 of N-methylpiperidine on iodomethane that precipitates N,N-dimethylpiperidinium iodide.
- Menshutkin reaction: triethylamine + iodoethaneDraw the SN2 attack of triethylamine on iodoethane that gives tetraethylammonium iodide.
- (S)-2-Azidopropylbenzene from (R)-1-phenylpropan-2-olDraw the mesylation of (R)-1-phenylpropan-2-ol with MsCl and Et3N, then the azide SN2 that gives (S)-(2-azidopropyl)benzene with inversion.
- Mesylation of cis-4-methylcyclohexanol keeps it cisDraw the mesylation of cis-4-methylcyclohexanol with MsCl and Et3N and show why the mesylate is still the cis isomer.
- Ethyl azide from ethanol via its mesylateDraw mesylation of ethanol with MsCl and Et3N, then the SN2 attack of azide that gives ethyl azide.
- trans-4-Methylcyclohexanol to cis sulfide via mesylateDraw the mesylation of trans-4-methylcyclohexanol and the SN2 attack of thiophenoxide that inverts the ring carbon to give the cis sulfide.
- Oxetane closure from 3-bromopropan-1-olDraw the deprotonation of 3-bromopropan-1-ol by hydroxide and the slow intramolecular SN2 that closes oxetane.
- PBr3 on (R)-1-cyclohexylethanol with inversionDraw the PBr3 mechanism that turns (R)-1-cyclohexylethanol into (S)-(1-bromoethyl)cyclohexane with inversion at the carbinol carbon.
- PBr3 on (S)-1-phenylethanol with inversionDraw the PBr3 mechanism that turns (S)-1-phenylethanol into (R)-(1-bromoethyl)benzene and show the backside attack at the benzylic carbon.
- (R)-2-Bromobutane from (S)-butan-2-ol and PBr3Draw the two substitutions that turn (S)-butan-2-ol into (R)-2-bromobutane with PBr3 and show the inversion at the carbinol carbon (2-butanol).
- PBr3 on (R)-3-methylbutan-2-ol: inversion, no shiftDraw the PBr3 mechanism that converts (R)-3-methylbutan-2-ol into (S)-2-bromo-3-methylbutane and explain why no hydride shift occurs.
- PBr3 converts cis-4-methylcyclohexanol to the trans bromideDraw the two substitutions by which PBr3 turns cis-4-methylcyclohexanol into trans-1-bromo-4-methylcyclohexane, and show the inversion at the ring carbon.
- Butyltriphenylphosphonium bromide from 1-bromobutaneDraw triphenylphosphine displacing bromide from 1-bromobutane to give butyltriphenylphosphonium bromide.
- Benzyltriphenylphosphonium bromide from PPh3 and benzyl bromideDraw the SN2 attack of triphenylphosphine on benzyl bromide that forms benzyltriphenylphosphonium bromide.
- Phosphonium salt from PPh3 and ethyl bromoacetateDraw triphenylphosphine attacking the α-carbon of ethyl bromoacetate by SN2 to form the (ethoxycarbonylmethyl)triphenylphosphonium salt.
- Pyrrolidine from 4-chlorobutan-1-amine ring closureDraw the intramolecular SN2 of the amine nitrogen of 4-chlorobutan-1-amine onto C–Cl and the carbonate deprotonation of the pyrrolidinium ion.
- 1-Methylcyclopentan-1-ol from 1-bromo-1-methylcyclopentaneDraw the SN1 hydrolysis of 1-bromo-1-methylcyclopentane in aqueous acetone: ionization, capture by water and deprotonation to 1-methylcyclopentan-1-ol.
- SN1 methanolysis of (1-bromopropyl)benzene racemizesDraw the SN1 methanolysis of enantiopure (1-bromopropyl)benzene and explain why the planar benzylic cation gives racemic (1-methoxypropyl)benzene.
- SN1 ethanolysis of 1-chloro-1-methylcyclohexaneDraw the SN1 ethanolysis of 1-chloro-1-methylcyclohexane: ionization to the tertiary cation, capture by ethanol and deprotonation to 1-ethoxy-1-methylcyclohexane.
- Tertiary cyclic chloride hydrolysisDraw ionization of 1-chloro-1-methylcyclohexane, capture of the ring cation by water, and deprotonation to 1-methylcyclohexan-1-ol.
- SN1 acetolysis of 1-chloro-1-methylcyclopentaneDraw the SN1 acetolysis of 1-chloro-1-methylcyclopentane: ionization, capture of the tertiary cation by the acetic acid carbonyl oxygen and deprotonation to 1-methylcyclopentyl acetate.
- SN1 hydrolysis of 1-chloro-1-phenylcyclohexaneDraw the SN1 hydrolysis of 1-chloro-1-phenylcyclohexane: ionization to the tertiary benzylic cation, capture by water and deprotonation to 1-phenylcyclohexan-1-ol.
- Ethanolysis of 1-phenylethyl bromide racemizesDraw ionization of enantiopure (1-bromoethyl)benzene, capture of the planar cation by ethanol, and deprotonation, giving racemic (1-ethoxyethyl)benzene.
- Acetolysis of a tertiary bromideDraw ionization of 2-bromo-2-methylbutane, capture of the tertiary cation by the carbonyl oxygen of acetic acid, and deprotonation to 2-methylbutan-2-yl acetate.
- Formolysis of 2-bromo-2-methylbutane by SN1Draw the SN1 formolysis of 2-bromo-2-methylbutane: ionization, capture of the tert-pentyl cation by formic acid, and deprotonation to 2-methylbutan-2-yl formate.
- 2-Ethoxy-2-methylpentane from 2-bromo-2-methylpentane (SN1)Draw the SN1 ethanolysis of 2-bromo-2-methylpentane: ionization to the tertiary cation, capture by ethanol and deprotonation to 2-ethoxy-2-methylpentane.
- SN1 hydrolysis of 2-chloro-2,4-dimethylpentaneDraw the SN1 hydrolysis of 2-chloro-2,4-dimethylpentane: ionization to the tertiary cation, capture by water and deprotonation to 2,4-dimethylpentan-2-ol.
- Hydrolysis of 3-chloro-3-ethylpentaneDraw ionization of 3-chloro-3-ethylpentane, capture of the tertiary cation by water, and deprotonation to 3-ethylpentan-3-ol.
- SN1 acetolysis of 3-iodo-3-methylheptane racemizesDraw the SN1 acetolysis of enantiopure 3-iodo-3-methylheptane and explain why the tertiary cation gives racemic 3-methylheptan-3-yl acetate.
- SN1 methanolysis of 4-methoxybenzyl chlorideDraw the SN1 methanolysis of 4-methoxybenzyl chloride: ionization to the methoxy-stabilized benzylic cation, capture by methanol and deprotonation to 1-methoxy-4-(methoxymethyl)benzene.
- SN1 hydrolysis of 4-tert-butyl-1-methylcyclohexyl chlorideDraw the SN1 hydrolysis of one diastereomer of 4-tert-butyl-1-methylcyclohexyl chloride and explain why the planar cation gives both cis and trans 4-tert-butyl-1-methylcyclohexan-1-ol.
- Allylic cation gives two alcoholsDraw ionization of 3-bromo-3-methylbut-1-ene, the resonance form of the allylic cation, capture by water at the primary end and deprotonation to 3-methylbut-2-en-1-ol.
- Diphenylmethanol by hydrolysis of bromodiphenylmethaneDraw the SN1 hydrolysis of bromodiphenylmethane: ionization to the diphenylmethyl cation, capture by water, and deprotonation to diphenylmethanol.
- Azide captures the benzhydryl cation (SN1)Draw the SN1 reaction of benzhydryl chloride with sodium azide in aqueous acetone: rate-determining ionization to the diphenylmethyl cation, then capture by azide to give benzhydryl azide.
- Benzhydryl ethyl ether by ethanolysis of benzhydryl chlorideDraw the SN1 ethanolysis of benzhydryl chloride: ionization to the diphenylmethyl cation, capture by ethanol, and deprotonation to benzhydryl ethyl ether.
- Benzyl chloride hydrolysis via benzyl cationDraw ionization of benzyl chloride to the benzyl cation, capture by water, and deprotonation to benzyl alcohol.
- Dimethoxymethane from MOMCl via an oxocarbenium ionDraw the SN1 methanolysis of chloromethyl methyl ether: oxygen-assisted loss of chloride to the oxocarbenium ion, addition of methanol and deprotonation to dimethoxymethane.
- 2-Phenylpropan-2-ol by SN1 hydrolysis of cumyl chlorideDraw the SN1 hydrolysis of cumyl chloride in aqueous acetone: ionization to the tertiary benzylic cation, capture by water and deprotonation to 2-phenylpropan-2-ol.
- Cyclohexyl formate by solvolysis of bromocyclohexane in formic acidDraw the SN1 formolysis of bromocyclohexane: ionization, capture of the cyclohexyl cation by formic acid, and deprotonation to cyclohexyl formate.
- SN1 vs E1: 1-chloro-1-methylcyclohexane in hot methanolDraw both fates of the cation from 1-chloro-1-methylcyclohexane in hot methanol: capture by methanol to 1-methoxy-1-methylcyclohexane (SN1) and loss of a ring β-hydrogen to 1-methylcyclohexene (E1).
- Competing SN1 and E1 in ethanolDraw ionization of tert-butyl bromide in hot ethanol, then ethanol removing a β-hydrogen from the cation to give 2-methylpropene (the E1 branch).
- SN1 ion pair: 1-(4-methylphenyl)ethyl chloride in methanolDraw the SN1 methanolysis of (S)-1-(1-chloroethyl)-4-methylbenzene and explain why the ion pair gives a mostly racemic methyl ether with a slight excess of inversion.
- SN1 ion pair: 1-phenylethyl chloride acetolysisDraw the SN1 acetolysis of (S)-(1-chloroethyl)benzene and explain why the ion pair gives 1-phenylethyl acetate with partial racemization and excess inversion.
- Ion-pair SN1 hydrolysis of 6-chloro-2,6-dimethyloctaneDraw the SN1 hydrolysis of enantiopure 6-chloro-2,6-dimethyloctane and explain why the contact ion pair gives 3,7-dimethyloctan-3-ol with more inversion than retention.
- Silver-assisted SN1 ethanolysis of 2-bromo-2-methylbutaneDraw the silver-assisted SN1 ethanolysis of 2-bromo-2-methylbutane: ionization pulled by Ag+ to give AgBr and the tertiary cation, capture by ethanol and deprotonation to 2-ethoxy-2-methylbutane.
- 2-Methoxy-2-methylbutane by methanolysis of 2-bromo-2-methylbutaneDraw the three SN1 steps for 2-bromo-2-methylbutane in methanol: ionization, capture of the tertiary cation by methanol, and deprotonation to 2-methoxy-2-methylbutane.
- SN1 of tert-butyl bromide in aqueous ethanol: two productsDraw the SN1 solvolysis of tert-butyl bromide in aqueous ethanol for two substrate molecules: one cation captured by water gives tert-butyl alcohol, the other captured by ethanol gives tert-butyl ethyl ether.
- SN1 of tert-butyl bromide in 2,2,2-trifluoroethanolDraw the SN1 solvolysis of tert-butyl bromide in 2,2,2-trifluoroethanol: ionization, capture of the tert-butyl cation by the solvent oxygen and deprotonation to the trifluoroethyl ether.
- tert-Butyl bromide hydrolysisDraw the three SN1 steps for tert-butyl bromide in water: ionization to the tert-butyl cation, capture of the cation by water, and deprotonation of the oxonium ion to tert-butyl alcohol.
- tert-Butyl acetate by acetolysis of tert-butyl chlorideDraw the SN1 acetolysis of tert-butyl chloride: ionization, capture of the tert-butyl cation by the carbonyl oxygen of acetic acid, and deprotonation to tert-butyl acetate.
- Azide captures the tert-butyl cationDraw ionization of tert-butyl chloride and capture of the tert-butyl cation by a terminal nitrogen of azide, giving 2-azido-2-methylpropane.
- tert-Butyl chloride ethanolysisDraw the three SN1 steps for tert-butyl chloride in ethanol: ionization, capture of the cation by ethanol, and deprotonation of the oxonium ion to tert-butyl ethyl ether.
- tert-Butyl methyl ether by methanolysis of tert-butyl iodideDraw the SN1 methanolysis of tert-butyl iodide: ionization to the tert-butyl cation, capture by methanol, and deprotonation to tert-butyl methyl ether.
- Trityl chloride methanolysisDraw ionization of triphenylmethyl chloride, capture of the trityl cation by methanol, and deprotonation to methoxytriphenylmethane.
- Triphenylmethanol from trityl chloride hydrolysisDraw the SN1 hydrolysis of trityl chloride in aqueous acetone: ionization to the trityl cation, capture by water and deprotonation of the oxonium ion to triphenylmethanol.
- Acetate O-alkylation by 1-bromobutaneDraw the SN2 step in which an acetate oxygen attacks 1-bromobutane, displacing bromide to give butyl acetate.
- 2-Oxo-2-phenylethyl acetate from phenacyl bromideDraw acetate displacing bromide from phenacyl bromide at the α-carbon to give 2-oxo-2-phenylethyl acetate.
- Hex-2-yne from 1-bromopropane and sodium propynideDraw the SN2 attack of the propynide carbanion on 1-bromopropane that forms the new C–C bond of hex-2-yne.
- 1-Methoxy-2,2-dimethylpropane from neopentyl bromideDraw methoxide displacing bromide from neopentyl bromide by a slow SN2 step to give 1-methoxy-2,2-dimethylpropane, and explain why no E2 alkene forms.
- Ammonia on benzyl bromide, then proton lossDraw ammonia displacing bromide from benzyl bromide to give a benzylammonium ion, then a second ammonia removing an N–H proton to release benzylamine.
- (3-Azidopropyl)benzene from 1-bromo-3-phenylpropaneDraw the one-step SN2 displacement of bromide from 1-bromo-3-phenylpropane by azide ion in DMF, giving (3-azidopropyl)benzene.
- Azide on 1-iodopentaneDraw the concerted backside attack of azide on the CH2–I carbon of 1-iodopentane with loss of iodide, giving 1-azidopentane.
- Azide on 2-iodohexane with inversionDraw azide attacking (S)-2-iodohexane from the back side to give (R)-2-azidohexane with inverted configuration.
- Benzyl azide from benzyl tosylate and sodium azideDraw the SN2 displacement of tosylate from benzyl tosylate by azide to give benzyl azide.
- Azide opens cyclohexene oxide: trans-2-azidocyclohexanolDraw backside attack of azide on cyclohexene oxide and protonation of the alkoxide by ammonium to give trans-2-azidocyclohexanol.
- Ethyl (R)-2-azidopropanoate by azide SN2 inversionDraw azide displacing bromide from ethyl (S)-2-bromopropanoate with backside attack to give ethyl (R)-2-azidopropanoate.
- 1-Azido-2,2-dimethylpropane from neopentyl triflateDraw the SN2 displacement of triflate from neopentyl triflate by azide in hot DMSO, giving 1-azido-2,2-dimethylpropane without rearrangement.
- 1-Bromooctane from 1-octyl mesylate and lithium bromideDraw bromide displacing mesylate from 1-octyl mesylate in one SN2 step to give 1-bromooctane.
- (R)-2-Bromooctane from (S)-2-octyl tosylate with LiBrDraw bromide displacing tosylate from (S)-2-octyl tosylate with backside attack, giving (R)-2-bromooctane with inverted configuration.
- Benzyl benzoate from benzyl bromide and sodium benzoateDraw benzoate displacing bromide from benzyl bromide in one backside SN2 step to give the ester benzyl benzoate.
- (S)-4-Phenylbutan-2-yl acetate via cesium acetate SN2Draw acetate displacing mesylate from (R)-4-phenylbutan-2-yl mesylate with backside attack to give (S)-4-phenylbutan-2-yl acetate.
- Benzyl chloride from benzyl mesylate and lithium chlorideDraw chloride displacing mesylate from benzyl mesylate by backside SN2 attack to give benzyl chloride.
- Hexanedinitrile from 1,4-dibromobutane by double SN2Draw both SN2 displacements of bromide from 1,4-dibromobutane by two cyanide ions in DMSO, giving hexanedinitrile.
- Cyanide displaces bromide, not chlorideDraw the SN2 step in which cyanide attacks the CH2Br carbon of 1-bromo-3-chloropropane and bromide leaves, giving 4-chlorobutanenitrile.
- Cyanide on 1-bromobutaneDraw the concerted SN2 step in which the carbon lone pair of cyanide attacks C1 of 1-bromobutane and bromide leaves, giving pentanenitrile (one carbon longer).
- Walden inversion: cyanide and (S)-1-bromo-1-deuteriobutaneDraw the backside SN2 attack of cyanide on (S)-1-bromo-1-deuteriobutane in DMSO and show the inverted product, (R)-2-deuteriopentanenitrile.
- 2-Methylpropanenitrile from 2-bromopropane and cyanideDraw the SN2 attack of cyanide on secondary 2-bromopropane in DMSO, giving 2-methylpropanenitrile, and explain why E2 is minor.
- Cyanide on 2-octyl mesylate with inversionDraw cyanide displacing mesylate from (R)-octan-2-yl mesylate with backside attack, giving (S)-2-methyloctanenitrile.
- (4-Methoxyphenyl)acetonitrile from 4-methoxybenzyl chlorideDraw the SN2 displacement of chloride from 4-methoxybenzyl chloride by cyanide in DMSO, giving (4-methoxyphenyl)acetonitrile.
- But-3-enenitrile from allyl chloride and sodium cyanideDraw cyanide displacing chloride directly at the CH2Cl carbon of allyl chloride to give but-3-enenitrile.
- Cyclopentanecarbonitrile from bromocyclopentaneDraw cyanide displacing bromide from bromocyclopentane by SN2 to give cyclopentanecarbonitrile.
- Ethyl 4-cyanobutanoate from ethyl 4-bromobutanoateDraw cyanide displacing bromide at C4 of ethyl 4-bromobutanoate to give ethyl 4-cyanobutanoate, leaving the ester untouched.
- Cyclohexanethiol from bromocyclohexane and NaSHDraw the one-step backside displacement of bromide from bromocyclohexane by hydrosulfide to give cyclohexanethiol.
- Bromocyclopentane from cyclopentyl tosylate and LiBrDraw the SN2 step in which bromide displaces tosylate from cyclopentyl tosylate in acetone to give bromocyclopentane.
- N,N-Dimethylethanamine from bromoethane and dimethylamineDraw the SN2 alkylation of dimethylamine by bromoethane and the proton transfer to a second dimethylamine that frees N,N-dimethylethanamine.
- Dimethylamine opens ethylene oxideDraw dimethylamine opening ethylene oxide by SN2, then the two proton transfers through water that give 2-(dimethylamino)ethanol.
- 3-Hydroxybutanenitrile from 2-methyloxirane and cyanideDraw cyanide opening 2-methyloxirane at the CH2 carbon and the protonation of the alkoxide that gives 3-hydroxybutanenitrile.
- Thiolate on 1-chloropropaneDraw the SN2 step in which ethanethiolate displaces chloride from 1-chloropropane to make ethyl propyl sulfide.
- Ethyl methyl sulfide from iodomethane and ethanethiolateDraw the SN2 methylation of ethanethiolate by iodomethane in ethanol, giving ethyl methyl sulfide.
- Ethanethiolate opens 2-methyloxirane at CH2Draw ethanethiolate attacking the less hindered CH2 of 2-methyloxirane and ethanol protonating the alkoxide to 1-(ethylthio)propan-2-ol.
- Ethoxide on benzyl chlorideDraw ethoxide displacing chloride from benzyl chloride in one step to form benzyl ethyl ether.
- 1-Fluorooctane from 1-octyl tosylate and TBAFDraw fluoride from TBAF displacing tosylate from 1-octyl tosylate by SN2 to give 1-fluorooctane.
- Benzyl fluoride from benzyl bromide, KF and 18-crown-6Draw the SN2 displacement of bromide from benzyl bromide by fluoride freed by 18-crown-6 in acetonitrile, giving benzyl fluoride.
- HS⁻ on 2-bromooctane with inversionDraw hydrosulfide displacing bromide from (S)-2-bromooctane with inversion to give (R)-octane-2-thiol.
- Hydrosulfide on 2-bromopropaneDraw the concerted backside attack of hydrosulfide on the secondary carbon of 2-bromopropane, giving propane-2-thiol.
- Hydroxide displaces bromide from 1-bromopropaneDraw the single concerted SN2 step in which hydroxide attacks the CH2 carbon of 1-bromopropane from the back side and bromide leaves, giving propan-1-ol.
- Benzyl alcohol from benzyl bromide and hydroxide (SN2)Draw the concerted SN2 displacement of bromide from benzyl bromide by hydroxide in aqueous THF, giving benzyl alcohol.
- Methanol from chloromethane and hydroxideDraw the single concerted SN2 step in which hydroxide replaces chloride on chloromethane to give methanol.
- Hydroxide on (chloromethyl)cyclohexaneDraw hydroxide displacing chloride from the CH2 carbon of (chloromethyl)cyclohexane to give cyclohexylmethanol.
- Hydroxide on 1-bromo-2-methylpropane (β-branched)Draw the SN2 step of hydroxide on 1-bromo-2-methylpropane, giving 2-methylpropan-1-ol, and recognize why β-branching slows it.
- trans-2-Bromocyclohexanol closes to cyclohexene oxideDraw hydroxide deprotonating trans-2-bromocyclohexan-1-ol, then the alkoxide attacking the neighbouring C–Br carbon from the back side to close cyclohexene oxide.
- Finkelstein on 2-bromobutane with inversionDraw iodide attacking (S)-2-bromobutane from the back side to give (R)-2-iodobutane with inversion of configuration.
- Iodide displaces tosylateDraw iodide attacking C1 of butyl tosylate and breaking the C–O bond, releasing tosylate and forming 1-iodobutane.
- Pentanenitrile from 1-chlorobutane with iodide catalysisDraw both SN2 steps by which catalytic iodide speeds the conversion of 1-chlorobutane to pentanenitrile, showing iodide regenerated.
- Ethyl iodoacetate from ethyl bromoacetate by FinkelsteinDraw iodide displacing bromide from ethyl bromoacetate in a Finkelstein SN2 step to give ethyl iodoacetate, with the ester carbonyl untouched.
- (Methylsulfanyl)cyclohexane from bromocyclohexaneDraw methanethiolate displacing bromide from bromocyclohexane by SN2 to give (methylsulfanyl)cyclohexane.
- Methoxide opens 2,2-dimethyloxirane at CH2Draw methoxide attacking the primary carbon of 2,2-dimethyloxirane and methanol protonating the tertiary alkoxide to 1-methoxy-2-methylpropan-2-ol.
- Methoxide on allyl bromideDraw methoxide displacing bromide from the CH2 carbon of allyl bromide in one step, giving 3-methoxyprop-1-ene with the C=C unchanged.
- Methoxide on bromoethaneDraw the one-step SN2 in which methoxide displaces bromide from bromoethane, making methoxyethane (bromoethane).
- Methoxide opens ethylene oxideDraw methoxide attacking a ring carbon of ethylene oxide to open the ring, then the alkoxide taking a proton from methanol to give 2-methoxyethanol.
- 3-Methoxyprop-1-yne from propargyl bromide and methoxideDraw methoxide displacing bromide from propargyl bromide by SN2 to give 3-methoxyprop-1-yne, leaving the terminal alkyne C–H intact.
- 1-Nitrooctane from 1-iodooctane and sodium nitriteDraw the SN2 attack of nitrite ion through nitrogen on 1-iodooctane in DMF, giving 1-nitrooctane, and explain why some octyl nitrite also forms.
- Butoxybenzene from 1-bromobutane and sodium phenoxideDraw phenoxide displacing bromide from 1-bromobutane in a Williamson SN2 step to give butoxybenzene.
- Allyl phenyl ether from phenol and allyl bromideDraw the deprotonation of phenol by carbonate and the SN2 attack of phenoxide on allyl bromide in acetone, giving allyl phenyl ether.
- Phenoxide opens ethylene oxide: 2-phenoxyethanolDraw sodium phenoxide opening ethylene oxide by backside attack and water protonating the alkoxide to 2-phenoxyethanol.
- Phenol → phenoxide → anisoleDraw hydroxide removing the O–H proton of phenol, then phenoxide oxygen attacking iodomethane to give anisole.
- Phenylacetylide alkylation of 1-bromo-3-methylbutaneDraw the SN2 attack of lithium phenylacetylide on 1-bromo-3-methylbutane, forming the new C–C bond of (5-methylhex-1-yn-1-yl)benzene.
- N-(2-Phenylethyl)phthalimide from (2-bromoethyl)benzeneDraw the SN2 N-alkylation of the phthalimide anion by (2-bromoethyl)benzene in DMF, giving N-(2-phenylethyl)phthalimide.
- Pyridine N-alkylation with 1-bromobutaneDraw the one-step SN2 in which the pyridine nitrogen attacks the CH2Br carbon of 1-bromobutane, giving N-butylpyridinium bromide.
- Trimethylsulfonium iodide from dimethyl sulfide and iodomethaneDraw the single SN2 step in which dimethyl sulfide attacks iodomethane to give trimethylsulfonium iodide.
- Benzyl phenyl sulfone from benzyl bromide and sulfinateDraw the S-alkylation of benzenesulfinate by benzyl bromide in DMF, explaining why the ambident anion reacts through sulfur to give benzyl phenyl sulfone.
- S-Benzyl ethanethioate from benzyl chloride and KSAcDraw thioacetate attacking benzyl chloride through sulfur in one SN2 step to give the thioester S-benzyl ethanethioate.
- Propyl thiocyanate from 1-bromopropane and KSCNDraw thiocyanate attacking 1-bromopropane through sulfur in one SN2 step to give propyl thiocyanate, and explain why sulfur rather than nitrogen bonds to carbon.
- Butyl phenyl sulfide from 1-bromobutane and thiophenolateDraw thiophenolate displacing bromide from 1-bromobutane in one SN2 step to give butyl phenyl sulfide.
- (S)-Butan-2-yl phenyl sulfide by SN2 inversionDraw thiophenolate displacing mesylate from (R)-butan-2-yl mesylate with backside attack to give (S)-butan-2-yl phenyl sulfide.
- trans-4-tert-Butylcyclohexyl phenyl sulfide by SN2Draw thiophenolate displacing the axial tosylate of cis-4-tert-butylcyclohexyl tosylate with inversion to give trans-4-tert-butylcyclohexyl phenyl sulfide.
- Menshutkin: Me3N + MeIDraw trimethylamine attacking iodomethane to form the tetramethylammonium ion and iodide.
- Phosphonium salt formationDraw triphenylphosphine attacking bromoethane to give the ethyltriphenylphosphonium ion and bromide.
- Water on iodomethane, then deprotonationDraw water attacking iodomethane to form a methyloxonium ion, then a second water removing a proton to give methanol.
- 1-Chloropropane from propan-1-ol with thionyl chlorideDraw the four arrow-pushing steps from propan-1-ol to 1-chloropropane with SOCl2 and pyridine: addition at sulfur, chloride loss, deprotonation by pyridine, and the SN2 that releases SO2 (propan-1-ol).
- SOCl2/pyridine on (S)-2-methylbutan-1-olDraw the four steps from (S)-2-methylbutan-1-ol to (S)-1-chloro-2-methylbutane with SOCl2 and pyridine and explain why the stereocenter is unchanged.
- SOCl2/pyridine on cis-4-tert-butylcyclohexanolDraw the four steps by which SOCl2 and pyridine convert cis-4-tert-butylcyclohexanol into trans-1-tert-butyl-4-chlorocyclohexane with inversion.
- SOCl2 and pyridine: (R)-octan-2-ol to (S)-2-chlorooctaneDraw the conversion of (R)-octan-2-ol to (S)-2-chlorooctane with SOCl2 and pyridine: addition at sulfur, chloride loss, deprotonation by pyridine and backside SN2 by chloride that releases SO2.
- SOCl2 without pyridine: (R)-octan-2-ol with retention (SNi)Draw the conversion of (R)-octan-2-ol to (R)-2-chlorooctane with SOCl2 and no pyridine: chlorosulfite formation, then front-side delivery of chloride through a tight ion pair (SNi) with retention.
- Benzyldimethylsulfonium bromide from dimethyl sulfideDraw dimethyl sulfide displacing bromide from benzyl bromide by SN2 to give benzyldimethylsulfonium bromide.
- Sulfonium salt from dimethyl sulfide and ethyl bromoacetateDraw dimethyl sulfide displacing bromide from ethyl bromoacetate to give (ethoxycarbonylmethyl)dimethylsulfonium bromide.
- Anisole from phenoxide and trimethylsulfoniumDraw phenoxide displacing dimethyl sulfide from the trimethylsulfonium ion to give anisole.
- S-Methyltetrahydrothiophenium iodide from THT and MeIDraw the SN2 attack of tetrahydrothiophene sulfur on iodomethane that forms S-methyltetrahydrothiophenium iodide.
- Thiirane formation from 2-chloroethanethiolDraw the deprotonation of 2-chloroethanethiol by hydroxide and the intramolecular SN2 that closes thiirane.
- Tosylation of (S)-butan-2-ol with retentionDraw the two steps that convert (S)-butan-2-ol into (S)-butan-2-yl tosylate with TsCl and pyridine, and explain why the stereocenter is retained.
- Cyclohexanecarbonitrile from cyclohexanol via its tosylateDraw tosylation of cyclohexanol with TsCl and pyridine, then the SN2 displacement of tosylate by cyanide to cyclohexanecarbonitrile.
- (R)-2-Iodohexane from (S)-hexan-2-ol via the tosylateDraw the tosylation of (S)-hexan-2-ol and the backside attack of iodide in acetone that gives (R)-2-iodohexane.
- Tosylation of (−)-menthol keeps its configurationDraw the tosylation of (−)-menthol with TsCl and pyridine, attack of oxygen at sulfur and deprotonation, and explain why menthyl tosylate keeps all three stereocentres.
- (S)-2-Azidopentane from (R)-pentan-2-ol via the tosylateDraw the tosylation of (R)-pentan-2-ol with TsCl and pyridine, then the SN2 attack of azide that inverts the stereocenter to give (S)-2-azidopentane.
- trans-4-tert-Butylcyclohexanol to the cis chlorideDraw the tosylation of trans-4-tert-butylcyclohexanol and the axial backside attack of chloride that gives cis-1-tert-butyl-4-chlorocyclohexane.
- Intramolecular Williamson: 4-bromobutan-1-ol to THFDraw the deprotonation of 4-bromobutan-1-ol by NaH and the intramolecular SN2 that closes tetrahydrofuran.
- Intramolecular Williamson to oxaneDraw hydroxide deprotonating 5-bromopentan-1-ol, then the alkoxide attacking the CH2Br carbon at the other end of the chain to close oxane.
- Williamson: ethoxide + 1-bromopropaneDraw the single SN2 step in which ethoxide attacks the CH2Br carbon of 1-bromopropane (substrate: 1-bromopropane), forming 1-ethoxypropane.
Predict the product 5
- Predict a rearranged capture productLocate a stabilizing hydride shift before solvent capture.
- Azide on 1-bromo-4-(bromomethyl)benzenePredict which of a benzylic and an aryl C–Br bond in the same molecule is replaced by azide.
- Which bromo alcohol cyclizes fastest?Predict the fastest intramolecular SN2 ring closure from the ring size formed.
- Pick the SN2 productPredict the configuration of an SN2 product from a chiral secondary bromide.
- Ambident cyanide: AgCN versus NaCN with 1-iodobutanePredict which atom of cyanide bonds to carbon when silver cyanide replaces sodium cyanide.
Classify 4
- Use a nucleophile concentration seriesDifferentiate simple SN1 and SN2 rate laws from controlled observations.
- Classify four substitutionsIdentify the substitution that proceeds by SN1 from substrate, nucleophile and solvent.
- Which atom of thiocyanate attacks an alkyl bromide?Identify the nucleophilic atom of the ambident thiocyanate ion in an SN2 reaction.
- Which bromide reacts with NaCN by SN2?Identify which of an aryl, vinyl, cyclopropyl and benzylic bromide can undergo SN2 with cyanide.
Compare 7
- Compare solvent effects on an anionic nucleophileExplain hydrogen-bond solvation as a nucleophilicity effect.
- Locate the steric bottleneckAssess neopentyl hindrance without misclassifying the leaving-group carbon.
- Rank leaving groupsRank common leaving groups by how easily they depart in substitution reactions.
- Halide nucleophiles in DMSORank halide nucleophilicity in a polar aprotic solvent, where the protic-solvent order reverses.
- Halide nucleophiles in methanolRank halide nucleophilicity in a protic solvent from solvation and polarizability.
- Rank SN2 ratesRank alkyl bromides by SN2 rate from steric hindrance at the reacting carbon.
- Rank tert-butyl chloride solvolysis rates by solventOrder SN1 solvolysis rates of a tertiary chloride by the ionizing power of the solvent.
Calculate 5
- ee after SN1 with partial inversionCalculate the enantiomeric excess of an SN1 product formed with partial inversion from ion pairing.
- Half-life of a first-order SN1 solvolysisCalculate the half-life of a first-order SN1 solvolysis from its rate constant.
- SN1 rate when the nucleophile triplesUse the first-order SN1 rate law to predict the effect of nucleophile concentration.
- Calculate an SN2 rate constant from one runCalculate a second-order SN2 rate constant from a measured rate and the reactant concentrations.
- Rate change on doubling both reactantsUse the second-order SN2 rate law to predict a rate change.
Find the error 2
- Repair an alcohol substitution proposalIdentify why hydroxyl activation is needed rather than simply adding a stronger donor.
- Find the error in a drawn SN2 transition stateDiagnose an incorrect drawing of the SN2 transition state by its geometry and charge distribution.
Interpret the evidence 3
- Separate inversion from a letter labelInfer geometric inversion without assuming unchanged CIP priority order.
- Hammond postulate: the SN1 ionization transition stateUse the Hammond postulate to describe the structure of the rate-determining SN1 transition state.
- Order in nucleophile from initial-rate dataDetermine the reaction order in the nucleophile from initial-rate data and identify the mechanism it implies.
Work backward 1
- Which bromide gives (R)-2-methylbutanenitrile?Work backward from a chiral SN2 product to the enantiomer of the alkyl bromide that forms it.
Plan a synthesis 3
- Williamson ether synthesis — choose the SN2 disconnectionSelect a Williamson disconnection that favors substitution over elimination.
- Plan a synthesis of cyclohexyl methyl sulfideChoose the SN2 disconnection of an unsymmetrical sulfide that puts the less hindered carbon on the electrophile.
- Choose the solvent for azide and 1-bromobutaneChoose the solvent that gives the fastest SN2 between an anionic nucleophile salt and a primary bromide.
Explain why 4
- Test a substrate-class boundaryDistinguish vinyl from saturated alkyl carbon in ordinary substitution.
- Why bromobenzene resists SN2 with methoxideExplain why an aryl bromide undergoes neither SN2 nor SN1 substitution.
- Solvent polarity and a neutral-reactant SN2Explain how solvent polarity affects an SN2 reaction between two neutral reactants.
- Phenoxide O- versus C-alkylation and solventExplain how a protic solvent shifts phenoxide alkylation from oxygen to the ring carbons.
Stuck on your own homework?
Snap it — first scan free, no sign-up
Scanning every week? Scan Standard: for about problems