Carboxylic Acids and Nitriles

Give IUPAC names for the following compounds:

Draw structures corresponding to the following IUPAC names:

(a) 2,3-Dimethylhexanoic acid 

(b) 4-Methylpentanoic acid

(c) trans-1,2-Cyclobutanedicarboxylic acid 

(d) o-Hydroxybenzoic acid

(e) (9Z,12Z)-9,12-Octadecadienoic acid 

(f) 2-Pentenenitrile

Assume you have a mixture of naphthalene and benzoic acid that you want to separate. How might you take advantage of the acidity of one component in the mixture to effect a separation?

The ${\mathbf{K}}_{\mathbf{a}}$ for dichloroacetic acid is$\mathbf{3}\mathbf{.}\mathbf{32}\mathbf{\times }{\mathbf{10}}^{\mathbf{-}\mathbf{2}}$. Approximately what percentage of the acid is dissociated in a 0.10 M aqueous solution?

Calculate the percentages of dissociated and undissociated forms present in the following solutions:

(a) ${}^{\mathbf{0}\mathbf{.}\mathbf{0010}\mathbf{ }\mathbf{M}}$ glycolic acid (${}^{{\mathbf{HOCH}}_{\mathbf{2}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}}$;${}^{{\mathbf{pK}}_{\mathbf{a}}\mathbf{=}\mathbf{3}\mathbf{.}\mathbf{83}}$ ) at ${}^{\mathbf{pH}\mathbf{=}\mathbf{4}\mathbf{.}\mathbf{50}}$

(b) ${}^{\mathbf{0}\mathbf{.}\mathbf{0020}\mathbf{ }\mathbf{M}}$ propanoic acid ( ${}^{{\mathbf{pK}}_{\mathbf{a}}\mathbf{=}\mathbf{4}\mathbf{.}\mathbf{87}}$ ) at ${}^{\mathbf{pH}\mathbf{=}\mathbf{5}\mathbf{.}\mathbf{30}}$

Which would you expect to be a stronger acid, the lactic acid found in tired muscles or acetic acid? Explain.

Dicarboxylic acids have two dissociation constants, one for the initial dissociation into a monoanion and one for the second dissociation into a dianion. For oxalic acid, ${\mathbf{HO}}_{\mathbf{2}}\mathbf{C}\mathbf{-}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$the first ionization constant is ${\mathbf{pK}}_{\mathbf{a}\mathbf{1}}\mathbf{=}\mathbf{1}\mathbf{.}\mathbf{2}$ and the second ionization constant is ${\mathbf{pK}}_{\mathbf{a}\mathbf{2}}\mathbf{=}\mathbf{4}\mathbf{.}\mathbf{2}$. Why is the second carboxyl group far less acidic than the first?

The ${\mathbf{pK}}_{\mathbf{a}}$ of p-cyclopropylbenzoic acid is 4.45. Is cyclopropylbenzene likely to be more reactive or less reactive than benzene toward electrophilic bromination? Explain.

Rank the following compounds in order of increasing acidity. Don’t look at a table of ${\mathbf{pK}}_{\mathbf{a}}$ data to help with your answer.

(a) Benzoic acid, p-methylbenzoic acid, p-chlorobenzoic acid

(b) p-Nitrobenzoic acid, acetic acid, benzoic acid

How would you prepare the following carboxylic acids?

(a)${\mathbf{\left(}{\mathbf{CH}}_{\mathbf{3}}\mathbf{\right)}}_{\mathbf{3}}\mathbf{ }{\mathbf{CCO}}_{\mathbf{2}}\mathbf{H}\mathbf{ }\mathbf{from}\mathbf{ }{\mathbf{\left(}{\mathbf{CH}}_{\mathbf{3}}\mathbf{\right)}}_{\mathbf{3}}\mathbf{ }\mathbf{CCI}$

(b) ${\mathbf{CH}}_{\mathbf{3}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}\mathbf{ }\mathbf{from}\mathbf{ }{\mathbf{CH}}_{\mathbf{3}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}\mathbf{Br}$ 

How might you prepare 2-phenylethanol from benzyl bromide? More than one step is needed.

How might you carry out the following transformation? More than one step is needed.

How would you prepare the following carbonyl compounds from a nitrile?

How would you prepare 1-phenyl-2-butanone, ${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{5}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{COCH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{3}}$, from benzyl bromide, ${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{5}}{\mathbf{CH}}_{\mathbf{2}}\mathbf{Br}$? More than one step is required.

Cyclopentane carboxylic acid and 4-hydroxycyclohexanone have the same formula (${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{10}}{\mathbf{O}}_{\mathbf{2}}$), and both contain an -OH and a C=O group. How could you distinguish between them using IR spectroscopy?

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

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

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

How might you carry out the following transformation? More than one step 

is needed.

How would you prepare the following carbonyl compounds from a nitrile?

(a)

(b)

How would you prepare 1-phenyl-2-butanone, ${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{5}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{COCH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{3}}$, from 

benzyl bromide,${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{5}}{\mathbf{CH}}_{\mathbf{2}}\mathbf{Br}$? More than one step is required.

Cyclopentanecarboxylic acid and 4-hydroxycyclohexanone have the 

same formula $\left(C_6{H}_{10}{O}_2\right)$, and both contain an -OH and a C=O group. How could 

you distinguish between them using IR spectroscopy?

How would you prepare 1-phenyl-2-butanone, C₆H₅CH₂COCH₂CH₃, from benzyl 

bromide, C₆H₅CH₂Br? More than one step is required?

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

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

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

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

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 each reaction below and write all of the steps involved in the acid-catalyzed  reaction, using curved arrows to represent electron flow in each step.

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occursby initial protonation of the nitrogen atom, followed by nucleophilicaddition of water. Review the mechanism of base-catalyzed nitrilehydrolysis in Section 20-7 and then predict the products for each reaction below and write all of the steps involved in the acid-catalyzedreaction, using curved arrows to represent electron flow in each step.

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

a.  Show the mechanism of the acetal hydrolysis and the structure of the cyanohydrins that results

b.  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-dimethylcyclopentane-carboxylic 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 section27-5, are biosynthesized by a pathway that involves loss of carbon dioxide 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:

1. cis-1,2-Cyclohexanedicarboxylic acid

2. Hepatanedioic acid

3. 2-Hexen-4-ynoic acid

4. 4-Ethyl-2-propyloctanoic acid

5. 3-chlorophthalic acid

6. Triphenylacetic acid

   
   

7. 2-Cyclobutenecarbonitrile

8. m-Benzoyl benzonitrile

Draw and name the following

1. The eight carboxylic acids with the formula ${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{12}}{\mathbf{O}}_{\mathbf{2}}$ 
2. Three nitriles with the formula ${\mathbf{C}}_{\mathbf{5}}{\mathbf{H}}_{\mathbf{7}}\mathbf{N}$ 

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 -${\mathbf{CH}}_{\mathbf{3}}{\mathbf{NH}}_{\mathbf{2}}$.) Draw the structure of pregabalin.

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-methyl hexanoic acid. (An aminomethyl group is - ${\mathbf{CH}}_{\mathbf{2}}{\mathbf{NH}}_{\mathbf{2}}$.) 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-hydroxypentane-dioic acid. Draw the structure.

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

20-36 Order the compounds in each of the following sets with respect to increasing acidity:

(a) Acetic acid, oxalic acid, formic acid

(b) p-Bromobenzoic acid, p-nitrobenzoic acid, 2,4-dinitrobenzoic acid

(c) Fluoroacetic acid, 3-fluoropropanoic acid, iodoacetic acid

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

(a) Magnesium acetate, magnesium hydroxide, methyl magnesium bromide

(b) Sodium benzoate, sodium p-nitrobenzoate, sodium acetylide

(c) Lithium hydroxide, lithium ethoxide, lithium formate

Calculate the pK_a's for the following acids:

(a) Lactic acid, Ka = 8.4 × 10^-4 

(b) Acrylic acid, Ka = 5.6 × 10^-6

Calculate the K_a's for the following acids:

(a) Citric acid, pKa = 3.14 

(b) Tartaric acid, pKa = 2.98

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

Thioglycolic acid,  ${\mathbf{HSCH}}_2{\mathbf{CO}}_2\mathbf{H}$, a substance used in depilatory agents
 (hair removers) has $\mathbf{pKa}\mathbf{=}\mathbf{3}\mathbf{.}\mathbf{42}$. What is the percent dissociation of
 thioglycolic acid in a buffer solution at $\mathbf{pH}\mathbf{=}\mathbf{3}\mathbf{.}\mathbf{0}$?

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?

In humans, the final product of purine degradation from DNA is uric acid, $\mathbf{pKa}=\mathbf{5}.\mathbf{61}$, which is excreted in the urine. What is the percentdissociation of uric acid in urine at a typical $\mathbf{pH}\mathbf{=}\mathbf{6}\mathbf{.}\mathbf{0}$? Why do you think uric acid is acidic even though it does not have a ${\mathbf{CO}}_2\mathbf{H}$ group?

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?