Question

How might you prepare the following esters using a nucleophilic acyl substitution reaction of an acid chloride? (a) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{CH}_{3}\) (b) \(\mathrm{CH}_{3} \mathrm{CO}_{2} \mathrm{CH}_{2} \mathrm{CH}_{3}\) (c) Ethyl benzoate

Short answer

React each acid chloride with the corresponding alcohol in the presence of a base to form esters.

Step-by-step solution

Understand the Reaction

Nucleophilic acyl substitution is a reaction where an acyl group (\(\mathrm{-CO-R}\)) in a compound is replaced by another nucleophile. In this case, an acid chloride (\(\mathrm{RCOCl}\)) is typically reacted with an alcohol in the presence of a base like pyridine or triethylamine to form an ester.

Identify the Components

For each ester provided, identify the alcohol component and the corresponding acid chloride:(a) For\(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{CO}_{2}\mathrm{CH}_{3}\), the alcohol is methanol (\(\mathrm{CH}_{3}\mathrm{OH}\)), and the acid chloride is propanoyl chloride (\(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{COCl}\)).(b) For\(\mathrm{CH}_{3}\mathrm{CO}_{2}\mathrm{CH}_{2}\mathrm{CH}_{3}\), the alcohol is ethanol (\(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{OH}\)), and the acid chloride is acetyl chloride (\(\mathrm{CH}_{3}\mathrm{COCl}\)).(c) For ethyl benzoate, the alcohol is ethanol and the acid chloride is benzoyl chloride (\(\mathrm{C}_{6}\mathrm{H}_{5}\mathrm{COCl}\)).

Perform the Reaction

React each acid chloride with the corresponding alcohol in the presence of a base:(a) For\(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{CO}_{2}\mathrm{CH}_{3}\): React propanoyl chloride with methanol.(b) For\(\mathrm{CH}_{3}\mathrm{CO}_{2}\mathrm{CH}_{2}\mathrm{CH}_{3}\): React acetyl chloride with ethanol.(c) For ethyl benzoate: React benzoyl chloride with ethanol.

Confirm Ester Formation

Ensure that the nucleophilic acyl substitution successfully forms the ester by checking the reaction conditions (presence of base to neutralize HCl formed) and monitoring reaction completion.

Key concepts

Acid Chloride

Acid chlorides, also known as acyl chlorides, are an essential class of organic compounds used extensively in acylation reactions. These compounds feature a carbon atom double-bonded to an oxygen atom ( --- RCOCl --- ). Near this carbonyl group is another bond to a chlorine atom. This setup makes acid chlorides very reactive, as the carbonyl carbon is easily attacked by nucleophiles. The chlorine atom acts as a good leaving group, which facilitates the substitution reaction. Acid chlorides are prepared by reacting carboxylic acids with reagents like thionyl chloride ( SOCl_2 ) or oxalyl chloride ( (COCl)_2 ). These reagents help replace the hydroxyl group with a chlorine atom. For example, propanoyl chloride ( CH_3CH_2COCl ) can be prepared from propanoic acid ( CH_3CH_2COOH ) and thionyl chloride. This reactivity of acid chlorides makes them ideal for forming various types of esters when they undergo nucleophilic acyl substitution.

Ester Formation

Ester formation through nucleophilic acyl substitution involves the reaction between an acid chloride and an alcohol. This is a common method to synthesize esters because acid chlorides offer high reactivity. During the reaction, the chlorine atom in the acid chloride is replaced by an alkoxy group from the alcohol, forming an ester bond. To illustrate, consider the conversion of propanoyl chloride ( CH_3CH_2COCl ) to methyl propanoate ( CH_3CH_2CO_2CH_3 ). Here, methanol ( CH_3OH ) acts as the nucleophile and attacks the carbonyl carbon of the acid chloride. This results in the cleavage of the carbon-chlorine bond and formation of the ester linkage. Some key points in ester formation include:

• The presence of a base (like pyridine) to neutralize the hydrochloric acid ( HCl ) byproduct.
• Ensuring the correct stoichiometry and conditions to favor the forward reaction.
• Monitoring the reaction progress to ensure complete conversion to the ester.

Organic Chemistry Reaction Mechanisms

Understanding reaction mechanisms in organic chemistry is essential for mastering complex transformations, such as nucleophilic acyl substitution. This reaction mechanism forms the basis for many synthetic techniques used in organic chemistry. In a typical nucleophilic acyl substitution of an acid chloride by an alcohol, the mechanism involves several clear steps: 1. **Nucleophilic Attack**: The oxygen atom of the alcohol, rich in electron pairs, attacks the carbon of the acid chloride's carbonyl group. This step results in a tetrahedral intermediate. 2. **Leaving Group Departure**: With the formation of the tetrahedral intermediate, the chlorine atom, a good leaving group, departs. This results in the formation of a new carbon-oxygen bond.
3. **Regeneration of the Carbonyl**: The double bond to oxygen is re-established, leading to the release of HCl . To complete the reaction cleanly, a base is often employed to absorb HCl , driving the reaction forward. Understanding this mechanism helps in predicting reaction outcomes and tweaking conditions for synthetic purposes.