Carboxylic Acids and Nitriles

Some pK_a data for simple dibasic acids are 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.
 (a) 1-Butanol (b) 1-Bromobutane (c) Pentanoic acid
(d) 1-Butene (e) Octane

How could you convert butanoic acid into the following compounds?

Write each step showing the reagents needed.

(a) 1-Butanol

(b) 1-Bromobutane

(c) Pentanoic acid

(d) 1-Butene 

(e) Octane

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

(a) 1-Butanol

(b) 1-Bromobutane 

(c) 1-Butene

(d) 1-Bromopropane 

(e) 4-Octene

How could you convert butanenitrile into the following compounds?

Write each step showing the reagents needed.

(a) 1-Butanol 

(b) Butylamine 

(c) 2-Methyl-3-hexanone

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

1. m-Chlorobenzoic acid
2. p-Bromobenzoic acid
3. Phenylacetic acid, C₆H₅CH₂CO₂H

Predict the product of the reaction of p-methyl benzoic acid with each of the following

1.  $\mathit{L}\mathit{i}\mathit{A}\mathit{l}{\mathit{H}}_{\mathbf{4}}\mathbf{,}\mathbf{ }\mathbf{then}\mathbf{ }\mathbf{ }{\mathit{H}}_{\mathbf{3}}{\mathit{O}}^{\mathbf{+}}$
2. N-Bromosuccinimide in $\mathit{C}\mathit{C}{\mathit{l}}_{\mathbf{4}}$
3. $\mathit{C}{\mathit{H}}_{\mathbf{3}}\mathit{M}\mathit{g}\mathit{B}\mathit{r}\mathit{ }\mathbf{ }\mathbf{in}\mathbf{ }\mathbf{ }\mathbf{ether}\mathbf{,}\mathbf{ }\mathbf{ }\mathbf{then}\mathbf{ }\mathbf{ }{\mathit{H}}_{\mathbf{3}}{\mathit{O}}^{\mathbf{+}}$
   
4.  $\mathit{K}\mathit{M}\mathit{n}{\mathit{O}}_{\mathbf{4}}\mathbf{,}\mathbf{ }\mathbf{ }{\mathit{H}}_{\mathbf{3}}{\mathit{O}}^{\mathbf{+}}$

Using ${}^{\mathbf{13}}\mathit{C}{\mathit{O}}_{\mathbf{2}}$ as your only source of labelled 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?

 ${\mathbf{H}}_{\mathbf{2}}\mathbf{C}\mathbf{=}\mathbf{CHCH}\mathbf{=}{\mathbf{CH}}_{\mathbf{2}}\stackrel{\mathbf{?}}{\mathbf{\to }}{\mathbf{H}}_{\mathbf{2}}{\mathbf{NCH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{CH}}_{\mathbf{2}}{\mathbf{NH}}_{\mathbf{2}}$

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

Propose a structure for a compound ${\mathbf{C}}_{\mathbf{6}}{\mathbf{H}}_{\mathbf{12}}{\mathbf{O}}_{\mathbf{2}}$ that dissolves in dilute NaOH and shows the following ¹H NMR spectrum: 1.08 $\mathbf{\delta }$(9H, singlet), 2.2 $\mathbf{\delta }$(2H, singlet), and 11.2 $\mathbf{\delta }$(1H, 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

a)  ${\mathbf{CH}}_{\mathbf{3}}{\left({\mathrm{CH}}_2\right)}_{\mathbf{3}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$ - Pentanoic acid

b)   ${\left({\mathrm{CH}}_3\right)}_{\mathbf{2}}{\mathbf{CHCH}}_{\mathbf{2}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$- 3-Methylbutanoic acid

c)  ${\left({\mathrm{CH}}_3\right)}_{\mathbf{3}}{\mathbf{CCO}}_{\mathbf{2}}\mathbf{H}$ -2,2-Dimethylpropanoic acid

How would you use NMR to distinguish between the following pairs of isomers?

Compound A, C₄H₈O₃, has infra-red 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-methyl pentane with NaCN, followed by hydrolysis of the product. After the reaction sequence was carried out, however, none of the desired products could be found. What do you suppose went wrong?

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

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

Propose a synthesis of the anti-inflammatory drug Fenclorac from phenyl cyclohexane. 

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

The following pKa values have been measured. Explain why a hydroxyl group in the para position decreases the acidity while a hydroxy group in the meta position increases the acidity.

The two ¹H NMR spectra shown here belong to crotonic acid (trans-${\mathbf{CH}}_{\mathbf{3}}\mathbf{CH}\mathbf{=}{\mathbf{CHCO}}_{\mathbf{2}}\mathbf{H}$) and methacrylic acid (${\mathbf{CH}}_{\mathbf{2}}\mathbf{=}\mathbf{C}\left({\mathrm{CH}}_3\right){\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$). Which spectrum corresponds to which acid? Explain.

The ¹H and ¹³C NMR spectra below belong to a compouns 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.

$$\begin{gathered} \mathbf{a}\mathbf{)}\mathbf{ }{\mathbf{C}}_{\mathbf{7}}{\mathbf{H}}_{\mathbf{12}}{\mathbf{O}}_{\mathbf{2}}\mathbf{,}\mathbf{ }\mathbf{25}\mathbf{.}\mathbf{5}\mathbf{\delta }\left(20\right)\mathbf{,}\mathbf{25}\mathbf{.}\mathbf{9}\mathbf{\delta }\left(20\right)\mathbf{,}\mathbf{29}\mathbf{\delta }\left(20\right)\mathbf{,}\mathbf{43}\mathbf{.}\mathbf{1}\mathbf{\delta }\left(30\right)\mathbf{,}\mathbf{183}\mathbf{\delta }\left(40\right) \\ \mathbf{b}\mathbf{)}\mathbf{ }{\mathbf{C}}_{\mathbf{8}}{\mathbf{H}}_{\mathbf{8}}{\mathbf{O}}_{\mathbf{2}}\mathbf{,}\mathbf{ }\mathbf{21}\mathbf{.}\mathbf{4}\mathbf{\delta }\left(1^o\right)\mathbf{,}\mathbf{128}\mathbf{.}\mathbf{3}\mathbf{\delta }\left(4^o\right)\mathbf{,}\mathbf{129}\mathbf{\delta }\left(3^o\right)\mathbf{,}\mathbf{129}\mathbf{.}\mathbf{7}\mathbf{\delta }\left(3^o\right)\mathbf{,}\mathbf{143}\mathbf{.}\mathbf{1}\mathbf{\delta }\left(4^o\right)\mathbf{,}\mathbf{168}\mathbf{.}\mathbf{2}\mathbf{\delta }\left(4^o\right) \end{gathered}$$

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.