Question

Fischer esterification cannot be used to prepare tert-butyl esters. Instead, carboxylic acids are treated with 2 -methylpropene in the presence of an acid catalyst to generate them. [R]C(=O)O [R]C(=O)OC(C)(C)C 2-Methylpropene A tert-butyl ester (Isobutylene) (a) Why does the Fischer esterification fail for the synthesis of tert-butyl esters? (b) Propose a mechanism for the 2-methylpropene method.

Short answer

Answer: Fischer esterification cannot be used to prepare tert-butyl esters because the bulky tert-butyl alcohol experiences significant steric hindrance, leading to a slow reaction rate and a low yield of the tert-butyl ester. An alternative mechanism for synthesizing tert-butyl esters involves using 2-methylpropene and a carboxylic acid in the presence of an acid catalyst. This method avoids the steric hindrance issue and allows for efficient synthesis of tert-butyl esters.

Step-by-step solution

Understanding Fischer esterification

Fischer esterification is a reversible reaction between a carboxylic acid and an alcohol, in the presence of an acid catalyst, to form an ester and water. The equilibrium of this reaction usually favors the formation of esters.

tert-Butyl groups

tert-Butyl esters are esters in which the alkyl group attached to the oxygen of the ester is tert-butyl. This group is bulky and hindered, with three methyl groups attached to a central carbon atom.

Steric hindrance

During Fischer esterification, the alcohol attacks the carbonyl group of the carboxylic acid to form a tetrahedral intermediate. The formation of a tert-butyl ester requires a bulky tert-butyl alcohol, which would face significant steric hindrance in reaching the carbonyl carbon of the carboxylic acid, leading to a very slow reaction rate and a low yield of the tert-butyl ester. #b) Mechanism for the 2-methylpropene method#

Protonation of the carboxylic acid

In the presence of an acid catalyst, the carboxylic acid is protonated at the carbonyl oxygen, forming a resonance-stabilized oxonium ion.

Nucleophilic attack by 2-methylpropene

The carbocationic oxonium ion is electrophilic and can now be attacked by the nucleophilic double bond of 2-methylpropene (isobutylene). This forms a new carbon-carbon bond and a positive charge on the oxygen atom of the carboxylic acid portion.

Deprotonation

The oxygen of the carboxylic acid portion, with a positive charge, now undergoes deprotonation. This process generates the tert-butyl ester and regenerates the acid catalyst for the next iteration of the reaction. By using 2-methylpropene instead of tert-butyl alcohol and a carbocationic mechanism, the steric hindrance problem faced during Fischer esterification is avoided, allowing for the efficient synthesis of tert-butyl esters.

Key concepts

tert-butyl esters

Tert-butyl esters are a class of organic compounds characterized by the presence of a tert-butyl group attached to the oxygen of the ester functional group.

The tert-butyl group consists of a central carbon atom bonded to three methyl groups, rendering it quite bulky. Due to the size of the tert-butyl group, tert-butyl esters are subject to steric hindrance, which impacts their reactivity and the approach needed for their synthesis. When it comes to their practical uses, tert-butyl esters are commonly employed in the production of pharmaceuticals, fragrances, and as protective groups in organic synthesis due to their stability under various conditions.

During synthesis, the conventional Fischer esterification process is unsuitable for forming these esters owing to the challenges associated with the steric hindrance imposed by the tert-butyl group. Therefore, alternative synthetic routes, such as reaction with 2-methylpropene in the presence of an acid catalyst, are employed to successfully create tert-butyl esters.

steric hindrance in organic synthesis

Steric hindrance is an important concept in organic chemistry that refers to the slowing down or prevention of a chemical reaction due to the spatial demands of substituents within a molecule.

In the context of Fischer esterification, steric hindrance arises when bulky groups, such as the tert-butyl group, impede the approach of reactants towards each other. Specifically, in esterification reactions, bulky alcohols or acids can hinder the nucleophilic attack on the carbonyl carbon, which is a crucial step in ester formation.

Steric Effects

The large tert-butyl group affects the reaction kinetics by reducing the effectiveness of the attacking nucleophile, often resulting in lower yields or completely halting the reaction. This necessitates the need for alternative methods, such as using less hindered reagents or employing different reaction mechanisms that can accommodate or bypass these steric obstacles.

carboxylic acid reactions

Carboxylic acids are versatile organic compounds that participate in a wide range of chemical reactions. Their reactivity stems from the carboxyl group, which consists of a carbonyl (C=O) and a hydroxyl (-OH) group attached to the same carbon.

One of the fundamental reactions involving carboxylic acids is their ability to form esters via esterification. The traditional Fischer esterification involves the reaction of a carboxylic acid with an alcohol, in the presence of an acid catalyst, to yield an ester and water.

Reactivity Influencers

The reactivity of a carboxylic acid in esterification is influenced by factors such as the nature of the substituents attached to the acid, the steric profile of the reactants, and the choice of catalyst. The acidity of the carboxyl group allows for activation by protonation in acidic conditions, facilitating nucleophilic attack by the alcohol. However, when steric hindrance is significant, as in the case with tert-butyl alcohols, alternative reactants and methods must be considered.

esterification mechanisms

Esterification mechanisms detail the step-by-step processes by which esters are formed from carboxylic acids and alcohols. The classic mechanism in Fischer esterification involves acid catalysis and proceeds through several key steps.

First, the acid catalyst protonates the carbonyl oxygen of the carboxylic acid, making the carbonyl carbon more electrophilic. Then, an alcohol molecule attacks this electrophilic center, forming a tetrahedral intermediate. This intermediate then undergoes proton transfers and eliminates water, ultimately leading to the formation of an ester.

However, alternative mechanisms, such as the one involving 2-methylpropene for tert-butyl ester synthesis, bypass the issues related to steric hindrance. Instead of an alcohol, the alkene 2-methylpropene acts as the nucleophile and attacks a protonated carboxylic acid to form the ester directly without requiring the tetrahedral intermediate that traditional alcohols would form. This alternative pathway illustrates the adaptability of esterification methods to overcome steric challenges.