Additional Problems

Give IUPAC names for the following carboxylic acids (reddish brown = Br):

Would you expect the following carboxylic acids to be more acidic or less acidic than benzoic acid? Explain. (Reddish brown = Br.)

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.

Predict the product(s) and write the mechanism of each of the following reactions:

Predict the product(s) and write the mechanism of each of the following reactions:

Predict the product(s) and write the mechanism of each of the following reactions:

Predict the product(s) and write the complete mechanism of each of the following reactions:

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7 and then predict the products for the following reactions. Write the steps involved in the acid-catalyzed reaction, using curved arrows.

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.

Naturally occurring compounds called cyanogenic glycosides, such as lotaustralin, release hydrogen cyanide, HCN, when treated with aqueous acid. The reaction occurs by hydrolysis of the acetal linkage to form a cyanohydrin, which then expels HCN and gives a carbonyl compound.

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.

Give IUPAC names for the following compounds:

Draw structures corresponding to the following IUPAC names:

Draw and name the following compounds:

Pregabalin, marketed as Lyrica, is an anticonvulsant drug that is also effective in treating chronic pain. The IUPAC name of pregabalin is (S)-3-(aminomethyl)-5-methylhexanoic acid. (An aminomethyl group is –CH₂NH₂.) Draw the structure of pregabalin.

Isocitric acid, an intermediate in the citric acid cycle of food metabolism, has the systematic name (2R,3S)-3-carboxy-2-hydroxypentanedioic acid. Draw the structure.

Order the compounds in each of the following sets with respect to increasing acidity:

Arrange the compounds in each of the following sets in order of increasing basicity:

Calculate the pK_a’s of the following acids:

Calculate the K_a’s of the following acids:

Thioglycolic acid, HSCH₂CO₂H, a substance used in depilatory agents (hair removers) has pK_a = 3.42. What is the percent dissociation of thioglycolic acid in a buffer solution at pH = 3.0?

In humans, the final product of purine degradation from DNA is uric acid, pK_a = 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 pK_a 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?

How could you convert butanoic acid into the following compounds? Write each step showing the reagents needed.

How could you convert each of the following compounds into butanoic acid? Write each step showing all reagents.

How could you convert butanenitrile into the following compounds? Write each step showing the reagents needed.

How would you prepare the following compounds from benzene? More than one step is needed in each case.

Predict the product of the reaction of p-methylbenzoic acid with each of the following:

Using ¹³CO₂ as your only source of labeled carbon, along with any other compounds needed, how would you synthesize the following compounds?

How would you carry out the following transformations?

Which method—Grignard carboxylation or nitrile hydrolysis—would you use for each of the following reactions? Explain.

1,6-Hexanediamine, a starting material needed for making nylon, can be made from 1,3-butadiene. How would you accomplish the synthesis?

3-Methyl-2-hexenoic acid (mixture of E and Z isomers) has been identified as the substance responsible for the odor of human sweat. Synthesize the compound from starting materials having five or fewer carbons.

Propose a structure for a compound C₆H₁₂O₂ that dissolves in dilute NaOH and shows the following ¹H NMR spectrum: 1.08 δ (9 H, singlet), 2.2 δ (2 H, singlet), and 11.2 δ (1 H, singlet).

What spectroscopic method could you use to distinguish among the following three isomeric acids? Tell what characteristic features you would expect for each acid.

How would you use NMR (either ¹³C or ¹H) to distinguish between the following pairs of isomers?

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.

A chemist in need of 2,2-dimethylpentanoic acid decided to synthesize some by reaction of 2-chloro-2-methylpentane with NaCN, followed by hydrolysis of the product. After the reaction sequence was carried out, however, none of the desired product could be found. What do you suppose went wrong?

Show how you might prepare the anti-inflammatory agent ibuprofen starting from isobutylbenzene. More than one step is needed.

The following synthetic schemes all have at least one flaw in them. What is wrong with each?

p-Aminobenzoic acid (PABA) was once widely used as a sunscreen agent. Propose a synthesis of PABA starting from toluene.

Propose a synthesis of the anti-inflammatory drug fenclorac from phenylcyclohexane.

The pK_a’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 pK_a = 4.19, which of the substituents are activators and which are deactivators?

How would you carry out the following transformations? More than one step is needed in each case.

The following pK_a 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:

The two ¹H NMR spectra shown here belong to crotonic acid (trans-CH₃CH$\text{=}$CHCO₂H) and methacrylic acid [H₂C$\text{=}$C(CH₃)CO₂H]. Which spectrum corresponds to which acid? Explain.

The ¹H and ¹³C NMR spectra below belong to a compound with formula C₆H₁₀O₂. Propose a structure for this compound.

Propose structures for carboxylic acids that show the following peaks in their ¹³C NMR spectra. Assume that the kinds of carbons (1°, 2°, 3°, or 4°) have been assigned by DEPT-NMR.

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.