Carbonyl Condensation Reactions

Using curved arrows to indicate the electron flow in each step, show how the base-catalyzed retro-aldol reaction of 4-hydroxy-4-methyl-2-pentanone takes place to yield 2 equivalents of acetone.

What enone product would you expect from aldol condensation of each of the following compounds?

Aldol condensation of 3-methyl cyclohexanone leads to a mixture of two enone products, not counting double-bond isomers. Draw them.

What enone product would you expect from aldol condensation of each of the following compounds?

Aldol condensation of 3-methyl cyclohexanone leads to a mixture of two enone products, not counting double-bond isomers. Draw them.

Which of the following compounds are aldol condensation products? What is the aldehyde or ketone precursor of each?

(a) 2-Hydroxy-2-methylpentanal      (b) 5-Ethyl-4-methyl-4-hepten-3-one

Which of the following compounds are aldol condensation products? What is the aldehyde or ketone precursor of each?

(a) 2-Hydroxy-2-methylpentanal      (b) 5-Ethyl-4-methyl-4-hepten-3-one

1-Butanol is prepared commercially by a route that begins with an aldol reaction. Show the steps that are likely to be involved.

Show how you would synthesize the following compound using an aldol reaction:

1-Butanol is prepared commercially by a route that begins with an aldol reaction. Show the steps that are likely to be involved.

Show how you would synthesize the following compound using an aldol reaction:

Which of the following compounds can probably be prepared by a mixed aldol reaction? Show the reactants you would use in each case.

Which of the following compounds can probably be prepared by a mixed aldol reaction? Show the reactants you would use in each case.

Treatment of a 1,3-diketone such as 2,4-pentanedione with base does not give an aldol condensation product. Explain.

What product would you expect to obtain from the base treatment of  1,6-cyclo-decanedione?

Treatment of a 1,3-diketone such as 2,4-pentanedione with base does not give an aldol condensation product. Explain.

Show the products you would expect to obtain by Claisen condensation of the following esters: (a) $\left(C{H}_{3}CHC{H}_{2}C{O}_{2}Et\right)$ (b) Ethyl phenylacetate (c) Ethyl cyclohexyl acetate

As shown in Figures 23-4, the Claisen reaction is reversible. That is, a 𝛃-keto ester can be cleaved by base into two fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs.

As shown in Figures 23-4, the Claisen reaction is reversible. That is, a 𝛃-keto ester can be cleaved by base into two fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs.

Show the products you would expect to obtain by Claisen condensation of the following esters: (a) (CH₃)₂CHCH₂CO₂Et   (b) Ethyl phenylacetate   (c) Ethyl cyclohexyl acetate

What product would you expect from the following mixed Claisen-like reaction?

What product would you expect from the following mixed Claisen-like reaction?

What product would you expect from the following reaction?

Dieckmann cyclization of diethyl 3-methylheptanedioate gives a mixture of two 𝛃-keto ester products. What are their structures, and why is a mixture formed?

Dieckmann cyclization of diethyl 3-methylheptanedioate gives a mixture of two 𝛃-keto ester products. What are their structures, and why is a mixture formed?

What product would you obtain from a base-catalyzed Michael reaction of 2,4-pentanedione with each of the following α-β unsaturated acceptors?

(a) 2-Cyclohexenone 

(b) Propenenitrile

(c) Ethyl 2-butenoate.

What product would you obtain from a base-catalyzed Michael reaction of 3-buten-2-one with each of the following nucleophilic donors?

How would you prepare the following compound using a Michael reaction?

What products would result after hydrolysis from the reaction of the enamine prepared from cyclopentanone and pyrrolidine with the following 𝛂-𝛃-unsaturated acceptors? 

(a) $H_{2}C=CHC{O}_{2}Et$ 

(b) $H_{2}C=CHCHO$

(c)$C{H}_{3}CH=CHCOC{H}_3$

Show how you might use an enamine reaction to prepare each of the following compounds:

How would you prepare the following compound using a Robinson annulation reaction between a 𝛃-diketone and an𝛂, 𝛃 -unsaturated ketone? Draw the structures of both reactants and the intermediate Michael addition product

What ketones or aldehydes might the following enones have been prepared from by aldol reaction?

The following structure represents an intermediate formed by the addition of an ester enolate ion to a second ester molecule. Identify the reactant, the leaving group, and the product.

The following molecule was formed by an intramolecular aldol reaction. What dicarbonyl precursor was used for its preparation?

The following molecule was formed by a Robinson annulation reaction. What reactants were used?

Predict the addition product for each reaction below and provide the mechanism.

Based on your answers to Problem 23-27, predict the dehydration product for each reaction and provide the mechanism.

Predict the product(s) and provide the mechanism for each reaction below.

Predict the product(s) and provide the mechanism for each reaction below.

Knoevenagel condensation is a reaction involving an active methylene compound (a CH₂ flanked by two electron-withdrawing groups) and an aldehyde and ketone. Propose a mechanism for the reaction below.

Azlactones are important starting materials used in the synthesis of dehydro a-aminoacids. They react with aldehydes to form an intermediate that is hydrolyzed under acidic conditions to give the final amino acid product. Provide the structure of the intermediate and propose a mechanism for its formation.

Leucine, one of the twenty amino acids found in proteins, is metabolized by a pathway that includes the following step. Propose a mechanism.

Isoleucine, another of the twenty amino acids found in proteins, metabolized by a pathway that includes the following step. Propose a mechanism.

The first step in the citric acid cycle of food metabolism is reaction of oxaloacetate with acetyl CoA to give citrate. Propose a mechanism, using acid or base catalysis as needed.

The amino acid leucine is biosynthesized from α-ketoisovalerate by the following sequence of steps. Show the mechanism of each.

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an α,β-unsaturated product. Show the mechanism for the Knoevenagel reaction of diethyl malonate with benzaldehyde.

The Darzens reaction involves a two-step, base-catalyzed condensation of ethyl chloroacetate with a ketone to yield an epoxy ester. The first step is a carbonyl condensation reaction, and the second step is an S_N2 reaction. Write both steps, and show their mechanisms.

The following reaction involves a hydrolysis followed by an intramolecular nucleophilic acyl substitution reaction. Write both steps, and show their mechanisms.

The following reaction involves an intramolecular Michael reaction followed by an intramolecular aldol reaction. Write both steps, and show their mechanisms.