Organic Chemistry 2 · Carboxyl and acyl chemistry
Claisen condensation and conjugate addition: practice problems
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Start drawing: Claisen condensation and conjugate addition
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- Annulate a ketone with methyl vinyl ketone
- Heptan-2-one by acetoacetic ester synthesis
- Ethyl 2-oxocyclopentanecarboxylate by Dieckmann condensation of diethyl adipate
- 3-Phenylpropanoic acid by malonic ester synthesis
- Claisen condensation — enolate acyl addition and elimination
- Michael addition — ester-enolate conjugate-addition stage
- Crossed Claisen condensation — acetate and benzoate through workup
- Crossed Claisen condensation — ester alpha-formylation
- Claisen condensation — ketone carbethoxylation
Draw the mechanism 85
- Claisen condensation — enolate acyl addition and eliminationForm a C–C bond with an enolate, then release ethoxide to restore the carbonyl.
- Michael addition — ester-enolate conjugate-addition stageRelay electron pairs through an enone during beta-carbon attack.
- Crossed Claisen condensation — acetate and benzoate through workupDistinguish donor enolate formation, acyl substitution, product trapping and acid workup in a complete crossed Claisen sequence.
- Crossed Claisen condensation — ester alpha-formylationUse an ester with a carbonyl-bound hydrogen as acceptor and preserve that hydrogen through acyl transfer and product trapping.
- Claisen condensation — ketone carbethoxylationForm a beta-ketoester from a ketone donor and carbonate acceptor without deleting the retained carbonate alkoxy group.
- Dieckmann condensation — adipate cyclization through workupCount the ring atoms in an intramolecular Claisen reaction and include the driving product deprotonation and workup.
- Michael addition — malonate and methyl vinyl ketoneMake a malonate enolate, add it to the beta carbon of an enone, and regenerate the base by proton transfer.
- Michael addition — acetoacetate and methyl acrylateDistinguish attack at the beta carbon from ester acyl substitution and retain all three carbonyl groups in the product.
- Intramolecular Michael addition — five-membered ring closureChoose the specified beta-carbon ring closure and finish with the saturated acceptor ketone, not an enolate endpoint.
- Malonic ester synthesis — two staged C-alkylationsComplete two separately staged malonate C-alkylations and recognize when the central carbon has no alpha hydrogen left.
- Acetoacetic ester synthesis — cyclic dialkylation stageLink intermolecular alkylation to a second deprotonation and five-membered intramolecular SN2 ring closure.
- Retro-Claisen reaction — hydrolytic acetylacetone cleavageRecognize a stabilized carbon leaving group in hydrolytic retro-Claisen cleavage and finish the acid–base trapping step.
- Lose CO₂ from a β-keto acidDraw the cyclic six-atom decarboxylation of a β-keto acid and finish the acid-catalyzed conversion of the enol to a ketone.
- Annulate a ketone with methyl vinyl ketoneCarry a ketone enolate through Michael addition, intramolecular aldol addition and E1cB dehydration to a fused cyclohexenone (a Robinson annulation).
- One pot, two Mannich reactions: tropinoneBuild the tropane bicycle from three starting molecules through two hemiaminal–iminium sequences, two enol Mannich reactions and two β-keto-acid decarboxylations with explicit proton accounting.
- Crossed Claisen of acetophenone with methyl propanoateDraw the methoxide enolisation of acetophenone, the acyl substitution at methyl propanoate, the deprotonation that drives the reaction, and the acid workup that gives 1-phenylpentane-1,3-dione.
- Crossed Claisen of 4-methylacetophenone with ethyl trifluoroacetateDraw how the enolate of 4-methylacetophenone is trifluoroacetylated by ethyl trifluoroacetate, including the deprotonation that drives the reaction and the acid workup to 4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione.
- Stork enamine allylation of cyclohexanoneDraw the C-alkylation of the pyrrolidine enamine of cyclohexanone by allyl bromide and the acid hydrolysis of the resulting iminium ion to 2-allylcyclohexanone.
- Hex-5-en-2-one by acetoacetic ester synthesisDraw the acetoacetic ester synthesis of hex-5-en-2-one: SN2 allylation of the acetoacetate enolate with allyl bromide, acid hydrolysis of the ester, decarboxylation and tautomerization.
- Levulinic acid by acetoacetic ester synthesisDraw the acetoacetic ester synthesis of levulinic acid: SN2 alkylation with ethyl bromoacetate, hydrolysis of the β-keto ester, decarboxylation, tautomerization and hydrolysis of the second ester.
- 3-Methyl-4-phenylbutan-2-one by acetoacetic dialkylationDraw the acetoacetic ester synthesis of 3-methyl-4-phenylbutan-2-one: methylation and then benzylation of the acetoacetate enolate, acid hydrolysis of the ester, decarboxylation and tautomerization.
- Heptan-2-one by acetoacetic ester synthesisDraw the full acetoacetic ester synthesis of heptan-2-one: enolate alkylation with 1-bromobutane, acid hydrolysis of the ester, decarboxylation and tautomerization.
- 4-Acetyl-5-oxohexanenitrile by Michael addition of pentane-2,4-dione to acrylonitrileDraw the triethylamine-promoted Michael addition of pentane-2,4-dione to acrylonitrile, including the proton return from triethylammonium.
- Propanoate and acetate by retro-Claisen cleavage of ethyl 2-methyl-3-oxobutanoateDraw the retro-Claisen cleavage of ethyl 2-methyl-3-oxobutanoate by concentrated hydroxide and the saponification that gives propanoate and acetate.
- Aza-Baylis–Hillman of an N-tosyl imine with MVKDraw the DABCO-catalysed aza-Baylis–Hillman reaction of an N-tosyl benzaldimine with methyl vinyl ketone: zwitterionic enolate formation, Mannich-type addition to the imine, proton relay and E1cB release of DABCO.
- Methyl 3-(piperidin-1-yl)propanoate by aza-Michael additionDraw the conjugate addition of piperidine to methyl acrylate and the two methanol-relayed proton transfers that give methyl 3-(piperidin-1-yl)propanoate.
- Barbital from diethyl diethylmalonate and ureaDraw the synthesis of barbital from diethyl diethylmalonate and urea: two nucleophilic acyl substitutions by urea nitrogens that close the six-membered ring, the deprotonation of the acidic product and the acidic workup.
- Baylis–Hillman of 4-nitrobenzaldehyde with acrylonitrileDraw the DABCO-catalysed Baylis–Hillman coupling of acrylonitrile with 4-nitrobenzaldehyde: conjugate addition of the amine, addition of the nitrile-stabilized carbanion to the aldehyde, proton relay and E1cB release of DABCO.
- Methyl 2-[hydroxy(phenyl)methyl]acrylate by Baylis–Hillman reactionDraw the DABCO-catalysed Baylis–Hillman coupling of methyl acrylate with benzaldehyde: conjugate addition, aldol addition, proton relay and E1cB release of DABCO.
- Benzoin by cyanide-catalysed benzoin condensationDraw the cyanide-catalysed benzoin condensation: cyanohydrin anion formation, umpolung deprotonation, addition to a second benzaldehyde and release of cyanide.
- Diethyl phenylmalonate from ethyl phenylacetateDraw the carbonate Claisen acylation of ethyl phenylacetate with diethyl carbonate: the benzylic enolate, addition to the carbonate, loss of ethoxide, the driving deprotonation and the workup to diethyl phenylmalonate.
- Benzoylacetone from acetophenone and ethyl acetateDraw the mixed Claisen in which the acetophenone enolate (from NaH) is acetylated by ethyl acetate, through product trapping and acidic workup.
- Ethyl acetoacetate from ethyl acetate (Claisen condensation)Draw every step of the self-Claisen condensation of ethyl acetate, including the deprotonation that drives it and the acidic workup, to give ethyl acetoacetate.
- Ethyl 2-ethyl-3-oxohexanoate by Claisen condensation of ethyl butanoateDraw the self-Claisen condensation of ethyl butanoate and track which carbon ends up between the two carbonyls of ethyl 2-ethyl-3-oxohexanoate.
- Claisen of ethyl isobutyrate with trityl sodiumDraw the Claisen condensation of ethyl isobutyrate driven by trityl sodium: irreversible enolate formation, addition to a second ester, loss of ethoxide and the workup to ethyl 2,2,4-trimethyl-3-oxopentanoate.
- Self-Claisen of ethyl phenylacetate to a β-keto esterDraw the self-Claisen condensation of ethyl phenylacetate: the benzylic ester enolate, its addition to a second ester, loss of ethoxide, the driving deprotonation and the workup to ethyl 3-oxo-2,4-diphenylbutanoate.
- Ethyl benzoylacetate by crossed Claisen of ethyl acetate and ethyl benzoateDraw the crossed Claisen in which the ethyl acetate enolate is benzoylated by ethyl benzoate, ending with product trapping and acidic workup.
- Crossed Claisen of cyclohexanone and diethyl oxalateDraw the crossed Claisen of cyclohexanone with diethyl oxalate: the ketone enolate, addition to an oxalate carbonyl, loss of ethoxide, the driving deprotonation and the workup to ethyl 2-oxo-2-(2-oxocyclohexyl)acetate.
- Formylation of cyclohexanone with ethyl formateDraw the Claisen formylation of cyclohexanone with ethyl formate: the ketone enolate, addition to the formate, loss of ethoxide, the driving deprotonation and an O-protonating workup to 2-(hydroxymethylene)cyclohexan-1-one.
- Crossed Claisen of ethyl propanoate and diethyl oxalateDraw the crossed Claisen condensation of ethyl propanoate with diethyl oxalate: the propanoate enolate, addition to an oxalate carbonyl, loss of ethoxide, the driving deprotonation and the workup to diethyl 2-methyl-3-oxosuccinate.
- Ethyl 2-methyl-3-oxopropanoate by formylation of ethyl propanoateDraw the crossed Claisen condensation in which the ethyl propanoate enolate is formylated by ethyl formate, through product trapping and workup.
- 3-Oxocyclohexane-1-carbonitrile by conjugate addition of cyanide to cyclohexenoneDraw the 1,4-addition of cyanide to cyclohex-2-en-1-one and the protonation of the resulting enolate by ammonium.
- Decarboxylation of benzylmalonic acid on heatingDraw the thermal decarboxylation of benzylmalonic acid: the six-membered cyclic loss of carbon dioxide to an enol, then the tautomerization of the enol to 3-phenylpropanoic acid.
- Ethyl 2-oxocyclopentanecarboxylate by Dieckmann condensation of diethyl adipateDraw the Dieckmann cyclization of diethyl adipate to ethyl 2-oxocyclopentanecarboxylate, including the product-trapping deprotonation and workup.
- Dieckmann regiochemistry of diethyl 2-methyladipateDraw the Dieckmann condensation of diethyl 2-methyladipate that leads to ethyl 3-methyl-2-oxocyclopentanecarboxylate, and explain why the ring closes from the unbranched end.
- Ethyl 2-oxocyclohexanecarboxylate from diethyl pimelateDraw the Dieckmann condensation of diethyl pimelate: enolate formation, ring closure onto the far ester, loss of ethoxide, the driving deprotonation and the acidic workup to ethyl 2-oxocyclohexanecarboxylate.
- Ethyl 2-oxocycloheptanecarboxylate from diethyl suberateDraw the Dieckmann condensation of diethyl suberate that closes a seven-membered ring: enolate formation, ring closure, loss of ethoxide, the driving deprotonation and the workup to ethyl 2-oxocycloheptanecarboxylate.
- Cyclohexanone from diethyl heptanedioate (Dieckmann condensation then decarboxylation)Draw the Dieckmann cyclization of diethyl heptanedioate and the acid hydrolysis, decarboxylation and tautomerization that convert the β-keto ester into cyclohexanone.
- Hajos–Parrish ketone by proline-catalysed aldolDraw the L-proline-catalysed intramolecular aldol of the Hajos–Parrish triketone (enamine formation, Houk–List C–C bond formation, hydrolysis) and the TsOH dehydration to the (S)-Hajos–Parrish ketone.
- Cyclohexane-1,3-dione from ethyl 5-oxohexanoateDraw the intramolecular Claisen condensation of ethyl 5-oxohexanoate: the methyl ketone enolate, six-membered ring closure onto the ester, loss of ethoxide, the driving deprotonation and the workup to cyclohexane-1,3-dione.
- Butan-2-one by ketonic cleavage of ethyl 2-methyl-3-oxobutanoateDraw the acid-catalysed hydrolysis of ethyl 2-methyl-3-oxobutanoate and the decarboxylation and tautomerization that give butan-2-one.
- Krapcho decarboxylation of diethyl benzylmalonateDraw the Krapcho decarboxylation of diethyl benzylmalonate: SN2 attack of chloride on an ethyl group, loss of carbon dioxide to an ester enolate, and protonation by water to ethyl 3-phenylpropanoate.
- Diethyl cyclobutane-1,1-dicarboxylate from diethyl malonateDraw the double alkylation of diethyl malonate with 1,3-dibromopropane: the first enolate and SN2, the second deprotonation, and the intramolecular SN2 that closes diethyl cyclobutane-1,1-dicarboxylate.
- Cyclopentanecarboxylic acid by malonic ester synthesisDraw the malonic ester synthesis of cyclopentanecarboxylic acid from 1,4-dibromobutane: two SN2 alkylations closing the ring, acid hydrolysis of both esters, decarboxylation and tautomerization.
- 3-Methylpentanoic acid by malonic ester synthesisDraw the malonic ester synthesis of 3-methylpentanoic acid: SN2 alkylation of the malonate enolate with 2-bromobutane, acid hydrolysis of both esters, decarboxylation and tautomerization.
- Cyclohexanecarboxylic acid by malonic ester synthesis with 1,5-dibromopentaneDraw the malonic ester route to cyclohexanecarboxylic acid: two enolate alkylations that close the ring, hydrolysis of both esters, decarboxylation and tautomerization.
- 2-Methyl-3-phenylpropanoic acid by malonic dialkylationDraw the malonic ester synthesis of 2-methyl-3-phenylpropanoic acid: methylation and then benzylation of the malonate enolate, acid hydrolysis of both esters, decarboxylation and tautomerization.
- 3-Phenylpropanoic acid by malonic ester synthesisDraw the malonic ester synthesis of 3-phenylpropanoic acid: benzylation of the malonate enolate, hydrolysis of both esters, decarboxylation and tautomerization.
- Mannich reaction of 3-pentanone with dimethylamineDraw the acid-catalysed Mannich reaction of 3-pentanone: iminium ion formation from dimethylamine and formaldehyde, enolization of the ketone and aminomethylation of one α-carbon.
- Mannich reaction of acetone with piperidine and formaldehydeDraw the acid-catalysed three-component Mannich reaction of acetone, formaldehyde and piperidine: methylenepiperidinium ion formation, enolization and C–C bond formation.
- Mannich reaction of acetophenone with dimethylamineDraw the acid-catalysed Mannich reaction of acetophenone: dimethyliminium ion formation, enolization of the methyl ketone and C–C bond formation to the β-amino ketone.
- 2-[(Dimethylamino)methyl]cyclohexan-1-one by Mannich reactionDraw the acid-catalysed Mannich reaction: iminium formation from dimethylamine and formaldehyde, enolization of cyclohexanone and C–C bond formation.
- Michael addition of 2-methylcyclohexanone to MVK at C2Draw the Michael addition of 2-methylcyclohexanone to methyl vinyl ketone through the more substituted (thermodynamic) enolate, building the quaternary carbon of 2-methyl-2-(3-oxobutyl)cyclohexan-1-one.
- Hajos–Parrish triketone by Michael addition to MVKDraw the triethylamine-catalysed Michael addition of 2-methylcyclopentane-1,3-dione to methyl vinyl ketone, giving the quaternary carbon of the Hajos–Parrish triketone.
- Michael addition of ethyl acetoacetate to acroleinDraw the Et3N-catalysed Michael addition of ethyl acetoacetate to acrolein: enolate formation, 1,4-addition that gives an aldehyde enolate, and protonation on carbon to ethyl 2-acetyl-5-oxopentanoate.
- Ethyl 2-acetyl-5-oxohexanoate by Michael addition of ethyl acetoacetate to methyl vinyl ketoneDraw the base-catalysed Michael addition of the ethyl acetoacetate enolate to methyl vinyl ketone and the proton transfer that regenerates ethoxide.
- 1,3,5-Triphenylpentane-1,5-dione by Michael addition of acetophenone to chalconeDraw the Michael addition of the acetophenone enolate to chalcone that builds the 1,5-diketone 1,3,5-triphenylpentane-1,5-dione.
- Michael addition of dimethyl malonate to cyclopentenoneDraw the methoxide-catalysed Michael addition of dimethyl malonate to the β-carbon of cyclopent-2-en-1-one and the protonation of the ring enolate.
- Michael addition of dimethyl malonate to a vinyl sulfoneDraw the methoxide-catalysed Michael addition of dimethyl malonate to phenyl vinyl sulfone: enolate formation, conjugate addition to the terminal CH2, and protonation of the α-sulfonyl carbanion by methanol.
- Michael addition of ethyl cyanoacetate to methyl acrylateDraw the ethoxide-catalysed Michael addition of ethyl cyanoacetate to methyl acrylate: enolate formation, conjugate addition and the proton transfer that regenerates ethoxide.
- Michael addition of diethyl malonate to 2-vinylpyridineDraw the Michael addition of diethyl malonate to 2-vinylpyridine, with the pyridine nitrogen taking the negative charge as an aza-enolate, and the protonation that restores the aromatic ring.
- Michael addition of diethyl malonate to acrylamideDraw the ethoxide-catalysed Michael addition of diethyl malonate to acrylamide: enolate formation, conjugate addition that gives an amide enolate, and protonation on carbon by ethanol.
- Diethyl 2-(3-oxocyclohexyl)malonate by Michael addition to cyclohexenoneDraw the Michael addition of the diethyl malonate enolate to the β-carbon of cyclohex-2-en-1-one and the protonation that regenerates ethoxide.
- Michael addition of diethyl malonate to ethyl crotonateDraw the Michael addition of the diethyl malonate enolate to the β-carbon of ethyl crotonate and the proton transfer from ethanol that regenerates ethoxide.
- Michael addition of diethyl malonate to trans-β-nitrostyreneDraw the Et3N-catalysed Michael addition of diethyl malonate to trans-β-nitrostyrene: enolate formation, conjugate addition that gives a nitronate, and protonation on carbon to diethyl 2-(2-nitro-1-phenylethyl)malonate.
- Michael addition of nitromethane to chalconeDraw the hydroxide-catalysed Michael addition of nitromethane to chalcone: nitronate formation, 1,4-addition to the enone and protonation of the ketone enolate.
- 5-Nitropentan-2-one by Michael addition of nitromethane to methyl vinyl ketoneDraw the DBU-catalysed Michael addition of the nitronate from nitromethane to methyl vinyl ketone, ending with the proton return from protonated DBU.
- Pseudopelletierine by Robinson–Schöpf double MannichDraw the one-pot Robinson–Schöpf synthesis of pseudopelletierine: iminium formation from glutaraldehyde and methylamine, two enol Mannich reactions that build the 9-azabicyclo[3.3.1]nonane, and two β-keto acid decarboxylations.
- Robinson annulation of 2-methylcyclohexanone with MVKDraw the Robinson annulation of 2-methylcyclohexanone with methyl vinyl ketone: Michael addition through the more substituted enolate, intramolecular aldol ring closure and E1cB dehydration to the octalone.
- Wieland–Miescher ketone by Robinson annulationDraw the Robinson annulation of 2-methylcyclohexane-1,3-dione with methyl vinyl ketone: Michael addition, intramolecular aldol ring closure and E1cB dehydration to the Wieland–Miescher ketone.
- Stetter reaction of benzaldehyde with acrylonitrileDraw the cyanide-catalysed Stetter reaction: cyanohydrin anion formation, umpolung deprotonation of the former aldehyde carbon, conjugate addition to acrylonitrile and release of cyanide.
- Methyl 3-(2-oxocyclohexyl)propanoate by Stork enamine Michael additionDraw the Stork enamine sequence: pyrrolidine enamine formation from cyclohexanone, conjugate addition to methyl acrylate, and hydrolysis to methyl 3-(2-oxocyclohexyl)propanoate.
- Stork enamine Robinson annulation of cyclohexanoneDraw the Stork enamine Robinson annulation: pyrrolidine enamine formation from cyclohexanone, Michael addition to methyl vinyl ketone, iminium hydrolysis, acid-catalysed intramolecular aldol and dehydration to the bicyclic enone.
- 3-(Phenylthio)cyclohexan-1-one by thia-Michael additionDraw the triethylamine-catalysed conjugate addition of thiophenol to cyclohex-2-en-1-one, including thiolate formation and proton return.
- Thiazolium-catalysed acyloin condensation of butanalDraw the thiazolium-catalysed acyloin condensation of two butanal molecules: ylide (carbene) formation, addition to the aldehyde, the Breslow intermediate, attack on a second butanal and release of the catalyst.
Predict the product 20
- Dieckmann condensation — count the adipate ringDetermine ring size from the donor alpha carbon and distal ester carbonyl.
- Acetoacetic ester synthesis with 1-bromopropanePredict the ketone made by propylating ethyl acetoacetate and then hydrolysing and decarboxylating it.
- Aza-Michael addition of diethylamine to methyl acrylatePredict the β-amino ester formed by conjugate addition of a secondary amine to an acrylate.
- Claisen of ethyl acetatePredict the β-keto ester formed by self-Claisen condensation of ethyl acetate.
- Self-Claisen of ethyl butanoatePredict which carbon bonds in the self-Claisen of a longer ester (ethyl butanoate).
- Carbethoxylation of cyclohexanonePredict the product of acylating cyclohexanone with diethyl carbonate.
- Formylation by ethyl formatePredict the crossed Claisen product of ethyl propanoate with ethyl formate.
- Oxalate acylation of acetonePredict the product of the crossed Claisen between acetone and diethyl oxalate.
- Dieckmann of diethyl adipatePredict the cyclic β-keto ester from Dieckmann cyclization of diethyl adipate.
- Knoevenagel condensation of cyclohexanone with malononitrilePredict the alkylidene product of a Knoevenagel condensation between a ketone and an active methylene compound.
- Malonic ester dialkylation with MeI, then EtBrPredict the α-branched carboxylic acid from two successive malonate alkylations.
- Malonic ester synthesis with benzyl bromidePredict the carboxylic acid formed by malonic ester synthesis with benzyl bromide.
- Malonic ester ring closure with 1,5-dibromopentanePredict the cyclic carboxylic acid formed when diethyl malonate is dialkylated by 1,5-dibromopentane and then hydrolysed and decarboxylated.
- Cyanoethylation of cyclohexanone enamine with acrylonitrilePredict the product of a Stork enamine Michael addition of cyclohexanone pyrrolidine enamine to acrylonitrile.
- Michael adduct of diethyl malonate and methyl vinyl ketonePredict the Michael adduct formed from diethyl malonate and methyl vinyl ketone.
- Perkin reaction of benzaldehyde with acetic anhydridePredict the α,β-unsaturated acid formed in a Perkin reaction of an aromatic aldehyde.
- Robinson annulation of cyclohexanone with MVKPredict the fused bicyclic enone formed by Robinson annulation of cyclohexanone with methyl vinyl ketone.
- Robinson annulation steps for 2-methylcyclohexanoneOrder the events of a Robinson annulation from the first enolate to the final enone.
- Stork enamine acylation of cyclohexanonePredict the 1,3-diketone formed by C-acylation of a cyclohexanone enamine and hydrolysis.
- Thia-Michael addition of ethanethiol to methyl vinyl ketonePredict the β-thio ketone formed by conjugate addition of a thiol to an enone.
Classify 8
- Distinguish two addition connectivitiesIdentify the functional-group outcome of direct versus conjugate addition to an enone.
- Which ketones the acetoacetic ester synthesis can makeClassify the products available from the acetoacetic ester synthesis as methyl ketones.
- Fatty acid synthase: acetoacetyl-ACP from malonyl-ACPClassify the ketoacyl synthase step of fatty acid synthesis as a decarboxylative Claisen condensation.
- Fumarase hydration of fumarate to (S)-malateClassify the fumarase-catalysed hydration of fumarate as a conjugate (Michael-type) addition.
- Choose the acceptorClassify ethyl benzoate's role in a crossed Claisen condensation.
- Mannich components of 3-(dimethylamino)propiophenoneClassify the three components that combine in a Mannich reaction and the role of each.
- Identify the Michael acceptor: cyclohex-2-en-1-oneClassify which alkene is activated toward conjugate addition because it is conjugated with a carbonyl group.
- Robinson annulation partner for a ketone enolateClassify methyl vinyl ketone as the reagent that supplies both the Michael acceptor and the aldol nucleophile in a Robinson annulation.
Compare 3
- Crossed Claisen condensation — select a non-enolizable acceptorSelect a non-enolizable ester electrophile for a crossed Claisen design.
- Claisen versus aldolContrast what happens to the tetrahedral alkoxide intermediate in a Claisen versus an aldol reaction.
- Rank Michael donors toward methyl vinyl ketoneOrder nucleophiles by how cleanly they give 1,4-addition (Michael addition) to an enone.
Calculate 4
- Claisen condensation — quantify product deprotonationEstimate the deprotonation equilibrium that drives a Claisen product toward its enolate.
- Dieckmann ring size from diethyl heptanedioateCount the ring size formed when diethyl heptanedioate undergoes Dieckmann cyclization.
- Carbonyl spacing in the cyclohexanone–MVK Michael adductCalculate the positional relationship of the two carbonyl carbons in a Michael adduct.
- Ring size in the Wieland–Miescher ketone annulationCalculate the size of the ring formed in a Robinson annulation by tracing which atoms come from each partner.
Find the error 2
- Claisen condensation limitations — the donor alpha-H requirementApply the product-deprotonation requirement to a donor with only one alpha H.
- Why diethyl glutarate fails the Dieckmann cyclizationDiagnose why diethyl pentanedioate gives no useful Dieckmann cyclization product.
Interpret the evidence 2
- Claisen condensation — identify the product-trapping protonIdentify the uniquely doubly stabilized alpha site in a beta-keto ester.
- Michael addition: which acceptor carbon the donor bonds toInterpret the resonance of an α,β-unsaturated ketone to locate the carbon that a Michael donor attacks.
Work backward 2
- Michael addition — disconnect a 1,5-dicarbonyl productMap a conjugate-addition product back to a beta-carbon acceptor and carbon donor.
- Hexanoic acid by malonic ester synthesis: choose the halideChoose the alkyl halide that gives hexanoic acid by malonic ester synthesis.
Plan a synthesis 3
- Claisen condensation — choose the matching alkoxideExplain the use of a matching alkoxide in a conventional Claisen condensation.
- Diethyl adipate to cyclopentanone: plan the sequencePlan the reagent sequence that converts diethyl hexanedioate into cyclopentanone.
- Plan a synthesis of 2-(3-oxobutyl)cyclohexan-1-onePlan a 1,5-diketone synthesis by Michael addition while avoiding the Robinson annulation that follows under strong base and heat.
Explain why 4
- How much ethoxide?Explain why a Claisen condensation needs a full equivalent of alkoxide base.
- Why acid at the endExplain the role of the acid workup after a Claisen condensation.
- Why heating makes a β-keto acid lose CO2Explain why β-keto acids decarboxylate on heating through a cyclic transition state and an enol intermediate.
- Phenyl vinyl ketone from a Mannich baseExplain how a β-amino ketone is converted into an α,β-unsaturated ketone by quaternization and E1cB elimination.
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