20 • Additional Problems
20 • Additional Problems
The following carboxylic acid can’t be prepared from an alkyl halide by either the nitrile hydrolysis route or the Grignard carboxylation route. Explain.
Electrostatic potential maps of anisole and thioanisole are shown. Which do you think is the stronger acid, p-methoxybenzoic acid or p-(methylthio)benzoic acid? Explain.
Nitriles can be converted directly to esters by the Pinner reaction, which first produces an iminoester salt that is isolated and then treated with water to give the final product. Propose a mechanism for the Pinner reaction using curved arrows to show the flow of electrons at each step.
Show the mechanism of the acetal hydrolysis and the structure of the cyanohydrin that results.
Propose a mechanism for the loss of HCN, and show the structure of the carbonyl compound that forms.
2-Bromo-6,6-dimethylcyclohexanone gives 2,2-dimethylcyclopentanecarboxylic acid on treatment with aqueous NaOH followed by acidification, a process called the Favorskii reaction. Propose a mechanism.
Naturally occurring compounds called terpenoids, which we’ll discuss in Section 27.5, are biosynthesized by a pathway that involves loss of CO2 from 3-phosphomevalonate 5-diphosphate to yield isopentenyl diphosphate. Use curved arrows to show the mechanism of this reaction.
In the Ritter reaction, an alkene reacts with a nitrile in the presence of strong aqueous sulfuric acid to yield an amide. Propose a mechanism.
Naming Carboxylic Acids and Nitriles
Acidity of Carboxylic Acids
In humans, the final product of purine degradation from DNA is uric acid, pKa = 5.61, which is excreted in the urine. What is the percent dissociation of uric acid in urine at a typical pH = 6.0? Why do you think uric acid is acidic even though it does not have a CO2H group?
Some pKa data for simple dibasic acids is shown. How can you account for the fact that the difference between the first and second ionization constants decreases with increasing distance between the carboxyl groups?
Reactions of Carboxylic Acids and Nitriles
How would you carry out the following transformations?
1,6-Hexanediamine, a starting material needed for making nylon, can be made from 1,3-butadiene. How would you accomplish the synthesis?
What spectroscopic method could you use to distinguish among the following three isomeric acids? Tell what characteristic features you would expect for each acid.
Compound A, C4H8O3, has infrared absorptions at 1710 and 2500 to 3100 cm–1 and has the 1H NMR spectrum shown. Propose a structure for A.
Show how you might prepare the anti-inflammatory agent ibuprofen starting from isobutylbenzene. More than one step is needed.
Propose a synthesis of the anti-inflammatory drug fenclorac from phenylcyclohexane.
The pKa’s of five p-substituted benzoic acids (YC6H4CO2H) are listed below. Rank the corresponding substituted benzenes (YC6H5) in order of their increasing reactivity toward electrophilic aromatic substitution. If benzoic acid has pKa = 4.19, which of the substituents are activators and which are deactivators?
The following pKa values have been measured. Explain why a hydroxyl group in the para position decreases the acidity while a hydroxyl group in the meta position increases the acidity.
Identify the missing reagents a–f in the following scheme:
Propose a structure for a compound, C4H7N, that has the following IR and 1H NMR spectra:
Carboxylic acids having a second carbonyl group two atoms away lose CO2 (decarboxylate) through an intermediate enolate ion when treated with base. Write the mechanism of this decarboxylation reaction using curved arrows to show the electron flow in each step.