Problem 12 - Basic Principles of Organic Chemistry

Question

Show how the following substances can be synthesized from the indicated starting materials: a. \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCN}\) from \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCl}\) (two ways) b. \(\mathrm{CH}_{3} \mathrm{CH}=\mathrm{CHCN}\) from \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{Br}\) c. \(\mathrm{CH}_{2}=\mathrm{CHCO}_{2} \mathrm{H}\) from \(\mathrm{CH}_{3} \mathrm{CHO}\)

Step-by-Step Solution

Answer

Use nucleophilic substitution and rearrangement for Parts a and b. Perform aldol condensation and oxidation for Part c.

Step 1: Identifying Reactants and Products for Part a

First, we need to analyze the transformation required to synthesize tert-butyl cyanide, \((\mathrm{CH}_3)_3 \mathrm{CCN}\), from tert-butyl chloride, \((\mathrm{CH}_3)_3 \mathrm{CCl}\). This will involve substituting the chlorine atom with a cyano group (CN).

Step 2: First Synthesis Route for Part a

One approach is to use sodium cyanide (NaCN) as a nucleophile in a nucleophilic substitution reaction. 1. Combine \((\mathrm{CH}_3)_3 \mathrm{CCl}\) with NaCN in a polar aprotic solvent like DMSO.2. The reaction proceeds through the \(S_N2\) mechanism, replacing Cl with CN.The equation is: \[(\mathrm{CH}_3)_3 \mathrm{CCl} + \mathrm{NaCN} \rightarrow (\mathrm{CH}_3)_3 \mathrm{CCN} + \mathrm{NaCl}\]

Step 3: Second Synthesis Route for Part a

Another method involves a two-step reaction:1. Perform an amination reaction by treating \((\mathrm{CH}_3)_3 \mathrm{CCl}\) with \(\mathrm{NH}_3\) to form \((\mathrm{CH}_3)_3 \mathrm{CNH}_2\).2. Convert \((\mathrm{CH}_3)_3 \mathrm{CNH}_2\) to \((\mathrm{CH}_3)_3 \mathrm{CCN}\) using an oxidizing agent like PDC (pyridinium dichromate).PDC will help in the dehydration of the primary amine to form the desired nitrile.

Step 4: Identifying Reactants and Products for Part b

Next, we need to form crotononitrile \(\mathrm{CH}_3 \mathrm{CH} = \mathrm{CHCN}\) from allyl bromide \(\mathrm{CH}_2 = \mathrm{CHCH}_2 \mathrm{Br}\). This requires adding a CN group to the terminal carbon.

Step 5: Reaction for Part b

A nucleophilic substitution reaction is ideal here:1. Treat \(\mathrm{CH}_2 = \mathrm{CHCH}_2 \mathrm{Br}\) with NaCN, which acts as a nucleophile.2. The reaction will proceed through SN2 to yield \(\mathrm{CH}_2 = \mathrm{CHCH}_2 \mathrm{CN}\).3. Finally, rearrange via tautomerization to obtain the desired product \(\mathrm{CH}_3 \mathrm{CHCH} = \mathrm{CN}\).

Step 6: Identifying Reactants and Products for Part c

Finally, for the synthesis of acrylic acid \(\mathrm{CH}_2 = \mathrm{CHCO}_2 \mathrm{H}\) from acetaldehyde \(\mathrm{CH}_3 \mathrm{CHO}\), we need a method to introduce both a carbon-carbon double bond and a carboxylic acid group.

Step 7: Reaction for Part c

A plausible method is aldol condensation followed by oxidation:1. Perform an aldol condensation using the acetaldehyde, which will initially form an aldol product \(\beta\)-hydroxybutyraldehyde.2. Dehydrate this aldol product to form 3-butenal (crotonaldehyde).3. Finally, oxidize 3-butenal to form acrylic acid using a strong oxidizing agent such as KMnO4 or a Pinnick oxidation with NaClO2.

Key Concepts

Nucleophilic Substitution

In organic chemistry, nucleophilic substitution is a fundamental concept involving the replacement of an atom or group in a molecule with a nucleophile. A nucleophile is a chemical species that donates an electron pair to form a chemical bond. In the context of the given problem, the nucleophile is sodium cyanide (NaCN), which is used to replace the chlorine atom in tert-butyl chloride i.e., \((\text{(CH}_3\text{)}_3\text{CCl}) \) to form tert-butyl cyanide, \((\text{(CH}_3\text{)}_3\text{CCN}) \). This reaction proceeds via the \( S_N2 \) mechanism:

• The \( S_N2 \) mechanism is a one-step process where the nucleophile attacks the carbon atom to which the leaving group (in this case, Cl) is attached.
• As the nucleophile bonds with the carbon, the leaving group is expelled at the same time, ensuring the transition state is semi-spherical, allowing optimal overlap.
• A polar aprotic solvent, such as dimethyl sulfoxide (DMSO), often facilitates \( S_N2 \) reactions as it stabilizes ions without forming hydrogen bonds.

Understanding these mechanisms is critical since precise reagent choice and conditions significantly impact the overall synthesis and yield of the desired product.

Aldol Condensation

Aldol condensation is a pivotal reaction in organic synthesis for forming carbon-carbon bonds, producing compounds with a new carbon-carbon double bond and hydroxyl group. It is particularly useful for synthesizing more complex molecules from simpler aldehyde or ketone units. In the provided exercise, acetaldehyde \( (\text{CH}_3\text{CHO}) \) is transformed into acrylic acid \( (\text{CH}_2 = \text{CHCO}_2\text{H}) \) through this reaction:

• Acetaldehyde undergoes a self-condensation reaction, initially forming an aldol product, \( \beta\text{-hydroxybutyraldehyde} \).
• Subsequently, dehydration occurs to form 3-butenal (crotonaldehyde), resulting in a new double bond.
• Finally, this resulting compound is further oxidized to synthesize acrylic acid.

The reaction often requires a base as a catalyst, such as hydroxide, to initiate the deprotonation of the aldehyde. Dehydration is usually driven by heating the intermediate product, which promotes the loss of water and formation of the double bond.Aldol reactions are highly versatile and form the basis for constructing diverse organic compounds, demonstrating the process’s indispensability for complex molecule synthesis.

Oxidation Reactions

Oxidation reactions involve the increase in oxidation state of a molecule, often by the addition of oxygen or the removal of hydrogen. These reactions are critical in organic synthesis to transform functional groups, such as converting alcohols or aldehydes to carboxylic acids. In this exercise, oxidation is the final step to convert 3-butenal (crotonaldehyde) to acrylic acid:

• Keen oxidizing agents include potassium permanganate \( \text{KMnO}_4 \) or sodium chlorite \( \text{NaClO}_2 \).
• The oxidation process increases the functional group’s carbon center from an aldehyde to a carboxylic acid, resulting in more stable molecules due to resonance within the carboxyl group.
• While performing oxidation, it's essential to control the environment, as excessive oxidation could further oxidize or break down the molecule.

This careful adjustment ensures the desired product is obtained without unwanted side reactions. Understanding oxidation's role in synthesis allows chemists to strategically modify molecules, enhancing product specificity and efficiency.