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. (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 fails for the synthesis of tert-butyl esters due to the steric hindrance caused by the highly branched structure of tert-butanol. This hinders the nucleophilic attack from the alcohol on the carbonyl carbon of the carboxylic acid, which is an essential step in Fischer esterification. The 2-methylpropene method overcomes this limitation by using a different nucleophile—2-methylpropene—to attack the carbonyl carbon, forming a new bond and generating a tert-butyl-carbocation intermediate. This intermediate leads to the formation of tert-butyl esters, circumventing the steric hindrance issue.

Step-by-step solution

(a) Analyzing Fischer Esterification)

Fischer esterification is a reaction between an alcohol and a carboxylic acid in the presence of an acid catalyst to form an ester and water. This reaction is an equilibrium process, and the equilibrium can be shifted by using excess alcohol or carboxylic acid. However, for tert-butyl esters, Fischer esterification fails. To understand why this is the case, we need to consider the structure of tert-butanol (the alcohol used to form tert-butyl esters). Tert-butanol has a highly branched structure with three methyl groups surrounding the alcohol's hydroxyl group. This steric hindrance prevents the nucleophilic attack from the alcohol on the carbonyl carbon of the carboxylic acid, which is the essential step in Fischer esterification. As a result, the reaction does not proceed effectively, and tert-butyl esters are not formed efficiently.

(b) 2-Methylpropene Method Mechanism)

Since Fischer esterification does not work for tert-butyl esters, an alternative method is needed. Carboxylic acids are treated with 2-methylpropene (also known as isobutylene) in the presence of an acid catalyst to generate tert-butyl esters. We can propose a mechanism for this reaction as follows: 1. Protonation of the carbonyl group: The acid catalyst protonates the carbonyl oxygen of the carboxylic acid, making the carbonyl carbon more electrophilic and susceptible to nucleophilic attack. 2. Nucleophilic attack by 2-methylpropene: The nucleophilic 2-methylpropene attacks the carbonyl carbon, forming a new bond between the carbonyl carbon and the carbon of 2-methylpropene. This leads to the formation of a tert-butyl-carbocation intermediate. 3. Deprotonation of the hydroxyl group: The hydroxyl group in the intermediate abstracts a proton from the acidic medium, generating a new carbonyl group and reforming the acid catalyst. 4. Protonation and elimination of water: The newly formed carbonyl oxygen is protonated again by the acid catalyst, and then the hydroxyl group on the adjacent carbon is deprotonated, creating a double bond and eliminating a water molecule. 5. Extraction of final product: An alcohol solvent is used to perform an extraction, and the tert-butyl ester is isolated as the final product. The 2-methylpropene method provides a reliable solution for the synthesis of tert-butyl esters, overcoming the steric hindrance problem encountered in Fischer esterification.

Key concepts

tert-Butyl Esters

Tert-butyl esters are chemical compounds where the ester functional group is connected to a tert-butyl group, also known as a tertiary butyl group. This group is composed of a central carbon atom bonded to three other carbon atoms, forming a highly branched, bulky structure. The synthesis of these compounds is of significant interest in organic chemistry due to their stability and utility as protective groups or as parts of more complex molecules.

However, the conventional Fischer esterification method is not suitable for synthesizing tert-butyl esters because the bulkiness of the tert-butyl group poses a challenge, known as steric hindrance, making it difficult for the necessary chemical reactions to occur under typical esterification conditions.

Steric Hindrance

Steric hindrance is a physical impediment to chemical reactions caused by the spatial arrangement of atoms within a molecule. In the context of tert-butyl esters, steric hindrance arises because the tert-butyl group is bulky, and its three methyl groups are close to the reactive site—the carbonyl carbon of the carboxylic acid. This crowding prevents the reactants from approaching each other in the correct orientation needed for the reaction to proceed. Such hindrance is a crucial concept in organic synthesis because it can dramatically affect reaction rates and the types of reactions that can feasibly occur.

2-Methylpropene Method

The 2-methylpropene method is a synthetic approach that circumvents the obstacles posed by Fischer esterification in the preparation of tert-butyl esters. This method utilizes 2-methylpropene (isobutylene) as a reactant instead of using an alcohol like tert-butanol. By reacting carboxylic acids with 2-methylpropene in the presence of an acid catalyst, this alternative procedure successfully synthesizes tert-butyl esters while overcoming the issues related to steric hindrance.

This method is valuable when the traditional Fischer esterification is impractical due to the bulk of reactants. The key lies in the ability of 2-methylpropene to attack the electrophilic center without the same level of repulsion experienced by larger, bulkier alcohols.

Nucleophilic Attack

Nucleophilic attack is a fundamental chemical process where a nucleophile, a species with a pair of electrons to donate, attacks an electrophilic center, a positively charged or electron-deficient site, to form a chemical bond. The nucleophile in this method is the 2-methylpropene, which is less hindered than tert-butanol, enabling it to attack the protonated carbonyl carbon of the carboxylic acid effectively. This leads to the formation of the tert-butyl-carbocation intermediate, crucial for the subsequent steps in the synthesis of tert-butyl esters by this method.

Acid Catalyst

An acid catalyst plays an essential role in chemical reactions by increasing the rate without being consumed in the process. It does so primarily by donating a proton to a reactant to make it more reactive, as seen in the 2-methylpropene method for synthesizing tert-butyl esters. The acid catalyst protonates the carbonyl group of the carboxylic acid, increasing its electrophilicity and enhancing its ability to undergo nucleophilic attack. The use of an acid catalyst is pivotal in organic synthesis for facilitating reactions that are otherwise too slow or thermodynamically unfavorable under neutral conditions.

Mechanism of Esterification

The mechanism of esterification describes the step-by-step process by which an acid and an alcohol (or a similar nucleophile) combine to form an ester. In the context of the 2-methylpropene method, it involves several distinct steps beginning with the protonation of the carboxylic acid, followed by nucleophilic attack, and culminating in the formation and subsequent deprotonation of intermediate carbocations. Each step plays a significant role in transforming the starting materials into the desired ester product, and understanding this mechanism is vital for students and chemists who aim to design and execute successful esterification reactions, particularly when traditional methods like Fischer esterification are not feasible due to steric hindrance.