23 • Additional Problems
23 • Additional Problems
The following structure represents an intermediate formed by 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?
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 α-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, is 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 was introduced in Problem 23-2. 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 SN2 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.
The following reaction involves a conjugate addition reaction followed by an intramolecular Claisen condensation. Write both steps, and show their mechanisms.
The following reaction involves an intramolecular aldol reaction followed by a retro aldol-like reaction. Write both steps, and show their mechanisms.
Propose a mechanism for the following base-catalyzed isomerization:
The Mannich reaction of a ketone, an amine, and an aldehyde is one of the few three-component reactions in organic chemistry. Cyclohexanone, for example, reacts with dimethylamine and acetaldehyde to yield an amino ketone. The reaction takes place in two steps, both of which are typical carbonyl-group reactions.
Cocaine has been prepared by a sequence beginning with a Mannich reaction (Problem 23-45) between dimethyl acetonedicarboxylate, an amine, and a dialdehyde. Show the structures of the amine and dialdehyde.
Propose a mechanism to account for the following reaction of an enamine with an alkyl halide:
Which of the following compounds would you expect to undergo aldol self-condensation? Show the product of each successful reaction.
(a) Trimethylacetaldehyde (b) Cyclobutanone (c) Benzophenone (diphenyl ketone)
(d) 3-Pentanone (e) Decanal (f) 3-Phenyl-2-propenal
Cinnamaldehyde, the aromatic constituent of cinnamon oil, can be synthesized by a mixed aldol condensation. Show the starting materials you would use, and write the reaction.
The following bicyclic ketone does not undergo aldol self-condensation even though it has two α hydrogen atoms. Explain.
Ethyl dimethylacetoacetate reacts instantly at room temperature when treated with ethoxide ion to yield two products, ethyl acetate and ethyl 2-methylpropanoate. Propose a mechanism for this cleavage reaction.
In contrast to the rapid reaction shown in Problem 23-60, ethyl acetoacetate requires a temperature over 150 °C to undergo the same kind of cleavage reaction. How can you explain the difference in reactivity?
Michael and Enamine Reactions
The so-called Wieland–Miescher ketone is a valuable starting material used in the synthesis of steroid hormones. How might you prepare it from 1,3-cyclohexanedione?
The Stork enamine reaction and the intramolecular aldol reaction can be carried out in sequence to allow the synthesis of cyclohexenones. For example, reaction of the pyrrolidine enamine of cyclohexanone with 3-buten-2-one, followed by enamine hydrolysis and base treatment, yields the product indicated. Write each step, and show the mechanism of each.
The following reaction involves two successive intramolecular Michael reactions. Write both steps, and show their mechanisms.
Fill in the missing reagents a–h in the following scheme:
The compound known as Hagemann’s ester is prepared by treatment of a mixture of formaldehyde and ethyl acetoacetate with base, followed by acid-catalyzed decarboxylation.
When 2-methylcyclohexanone is converted into an enamine, only one product is formed despite the fact that the starting ketone is unsymmetrical. Build molecular models of the two possible products and explain the fact that the sole product is the one with the double bond opposite the methyl-substituted carbon.