Chapter 26, Problem 26.39AP

Interpretation Introduction

(a)

Interpretation:

The synthesis of the given product from pyridine is to be predicted.

Concept introduction:

The replacement or substitution of one functional group with another different functional group in any chemical reaction is termed as a substitution reaction. In a nucleophilic substitution reaction, nucleophile takes the position of leaving the group by attacking the electron-deficient carbon atom.

Answer to Problem 26.39AP

The synthesis for the given product from pyridine is shown below.

Explanation of Solution

In the first step, pyridine undergoes oxidation on nitrogen atom to form $\text{pyridine-N-oxide}$ on reaction with $\text{30}\text{\%}{\text{H}}_{\text{2}}{\text{O}}_{\text{2}}$ solution.

In the second step, the treatment of $\text{pyridine-N-oxide}$ with ${\text{Me}}_{\text{3}}\text{SiCN,}{\text{Et}}_{\text{3}}\text{N,}\text{MeCN}$ followed by ${\text{Me}}_{\text{3}}\text{SiOH}$ occurs and it undergoes a nucleophilic aromatic substitution reaction. The substitution of cyanide group at position $\text{-2}$ is the major product which is named as $\text{2-cyanopyridine}$. However, the ${\text{Me}}_{\text{3}}\text{SiOH}$ is used as a reducing agent to convert the $\text{pyridine-N-oxide}$ to pyridine.

In the final step, the reduction of $\text{2-cyanopyridine}$ with the help of lithium aluminum hydride takes place to form the given product. The steps of conversion are shown below.

Figure 1

Conclusion

The synthesis for the given product from pyridine is shown in Figure 1.

Interpretation Introduction

(b)

Interpretation:

The synthesis of the given product from pyridine is to be predicted.

Concept introduction:

The formation of diazonium salt from aromatic amines takes place using sodium nitrite and hydrochloric acid at low temperatures. This process is known as diazotization.

The addition of the nitro group is known as nitration.

Answer to Problem 26.39AP

The synthesis for the given product from pyridine is shown below.

Explanation of Solution

In the first step, pyridine undergoes oxidation on nitrogen atom to form $\text{pyridine-N-oxide}$ on reaction with $\text{30}\text{\%}{\text{H}}_{\text{2}}{\text{O}}_{\text{2}}$ solution. In the second step, $\text{pyridine-N-oxide}$ with the nitric acid undergoes nitration reaction at the fourth position to form $\text{4-nitropyridine-N-oxide}$.

In the third step, the reduction of $\text{4-nitropyridine-N-oxide}$ takes place with the help of ${\text{H}}_{\text{2}}\text{,}\text{Pd}/\text{C}$ in which nitro group and $\text{N-oxide}$ group gets reduced.

In the fourth step, $\text{4-aminopyridine}$ reacts with ${\text{NaNO}}_{\text{2}}\text{,}\text{HCl}$ followed by reaction with $\text{CuBr}$ and gives $\text{4-bromopyridine}$.

In the fifth step, $\text{4-bromopyridine}$ with sodium ethylthiolate in presence of methanol undergoes nucleophilic substitution to form the desired product.

The overall reaction is shown below.

Figure 2

Conclusion

The synthesis for the given product from pyridine is shown in Figure 2.

Interpretation Introduction

(c)

Interpretation:

The synthesis of the given product from furfural is to be predicted.

Concept introduction:

Grignard reagents are organometallic compounds which are prepared using alkyl halides in the presence of magnesium metal in dry ether. These reagents act as strong nucleophiles and bases. Grignard reagents react with carbonyl compounds to form alcohol.

Answer to Problem 26.39AP

The synthesis of the given product from furfural is shown below.

Explanation of Solution

In the first step, the treatment of fufural with ${\text{CH}}_{\text{3}}\text{MgBr}$ followed by acid hydrolysis takes place.

In the second step, the product obtained with the help of pyridinium chlorochromate undergoes oxidation to form the corresponding ketone compound.

In the final step, methyl ketone reacts with the furfural in the presence of $\text{NaOH}$ solution to form $\text{α,β-unsaturated}$ carbonyl compound. This reaction is known as aldol condensation.

The overall reaction is shown below.

Figure 3

Conclusion

The synthesis of the given product from furfural is shown in Figure 3.

Interpretation Introduction

(d)

Interpretation:

The synthesis of the given product from furfural is to be predicted.

Concept introduction:

The replacement or substitution of one functional group with another different functional group in any chemical reaction is termed as a substitution reaction. In a nucleophilic substitution reaction, nucleophile takes the position of leaving the group by attacking the electron-deficient carbon atom.

Answer to Problem 26.39AP

The synthesis of the given product from furfural is shown below.

Explanation of Solution

In the first step, the reaction of furfural with ${\text{KMnO}}_{\text{4}}$ solution undergoes oxidation reaction to form furoic acid.

In the second step, furoic reacts acid with thionyl chloride to form furoyl chloride. The type of reaction is nucleophilic acyl substitution reaction.

In the third step, furoyl chloride with $\text{1-propanol}$ in the presence of trimethylamine undergoes esterification to form the desired product.

The overall reaction is shown below.

Figure 4

Conclusion

The synthesis of the given product from furfural is shown in Figure 4.

Interpretation Introduction

(e)

Interpretation:

The synthesis of the given product from $\text{3-methylpyridine}$ is to be predicted

Concept introduction:

Oxidation is the process of addition of oxygen. Oxidation is also defined as loss of electrons. In the oxidation process, there is increasing in the oxidation state. The acid is added in the reaction for protonation.

The oxidizing agent is defined as the species which oxidizes others and itself gets reduced.

Answer to Problem 26.39AP

The synthesis of the given product from $\text{3-methylpyridine}$ is shown below.

Explanation of Solution

In the first step, $\text{3-methylpyridine}$ with ${\text{KMnO}}_{\text{4}}$ forms nicotine as product.

In the second step, the reaction between nicotinic acid and thionyl chloride takes place in the presence of ethanol and gives the corresponding methyl ester as product.

In the third step, the reaction between methyl ester with hydrazine in the presence of ${\text{NaNO}}_{\text{2}}\text{,}\text{HCl}$ takes place and forms the corresponding acyl azide.

In the fourth step, the acyl azide on heating with benzene gives isocyanate as the product.

In the fifth step, the isocyanate is treated with $\text{pyridin-3-amine}$ to give the desired product.

Figure 5

Conclusion

The synthesis of the given product from $\text{3-methylpyridine}$ is shown in Figure 5.

Interpretation Introduction

(f)

Interpretation:

The synthesis of the given product from $\text{4-ethylpyridine}$ is to be predicted.

Concept introduction:

The replacement or substitution of one functional group with another different functional group in any chemical reaction is termed as a substitution reaction. In a nucleophilic substitution reaction, nucleophile takes the position of leaving the group by attacking the electron-deficient carbon atom.

Answer to Problem 26.39AP

The synthesis of the given product from $\text{4-ethylpyridine}$ is shown below.

Explanation of Solution

In the first step, the reaction of $\text{4-ethylpyridine}$ with methyl iodide undergoes methylation at nitrogen atom to form $\text{N-methyl-4-ethyl}$ pyridinium iodide as product.

In the second step, $\text{N-methyl-4-ethyl}$ pyridinium iodide with triethylamine undergoes abstraction of a proton from ethyl carbon of pyridine. The resulting anion is stabilized by resonance with the help of electronegative nitrogen atom, followed by the nucleophilic substitution reaction with the vinyl nitrile to form the desired product.

The overall reaction is shown below.

Figure 6

Conclusion

The synthesis of the given product from $\text{4-ethylpyridine}$ is shown in Figure 6.

Interpretation Introduction

(g)

Interpretation:

The synthesis of the given product from $\text{2-methylpyridine}$ is to be predicted.

Concept introduction:

The replacement or substitution of one functional group with another different functional group in any chemical reaction is termed as a substitution reaction. In a nucleophilic substitution reaction, nucleophile takes the position of leaving the group by attacking the electron-deficient carbon atom.

Answer to Problem 26.39AP

The synthesis of the given product from $\text{2-methylpyridine}$ is shown below.

Explanation of Solution

In the first step, $\text{2-methylpyridine}$ with $1$ equivalent of butyl lithium undergoes abstraction of proton from methyl group to form resonanace stabilized anion.

In the second step, the treatment of resonance stabilized anion with sodium cyanide followed by hydrolysis gives a carboxylic acid product.

In the third step, the treatment of $\text{2-}\left(\text{pyridin-2-yl}\right)\text{acetic acid}$ with $2$ equivalents of butyl lithium undergoes proton abstraction at the methylene carbon to form resonance stabilized anion.

In the final step, the resonance stabilized anion undergoes a nucleophilic substitution reaction with propyl bromide to form the desired product.

The overall reaction is shown below.

Figure 7

Conclusion

The synthesis of the given product from $\text{2-methylpyridine}$ is shown in Figure 7.