Question

Write the steps that could plausibly take place in the reaction of a primary alcohol with phosphorus tribromide in the presence of the weak base pyridine to give an alkyl bromide.

Short answer

The primary alcohol reacts with \(PBr_3\) via an SN2 mechanism to form an alkyl bromide and dibromophosphite.

Step-by-step solution

Protonation of the Alcohol

In the presence of pyridine, a weak base, the alcohol does not undergo stepwise deprotonation. Instead, the hydroxyl group of the primary alcohol remains intact at the start.

Formation of the Phosphorus Tribromide Intermediate

Phosphorus tribromide (\(PBr_3\)) is combined with the alcohol, allowing it to react with the hydroxyl group. The phosphorus atom in \(PBr_3\), which is electrophilic, is attacked by the lone pair on the oxygen of the alcohol, forming a phosphite ester intermediate and resulting in the loss of one bromide ion.

Nucleophilic Attack by Bromide Ion

The bromide ion, released during the formation of the phosphite ester, attacks the carbon atom bonded to the oxygen, which is now a good leaving group due to its attachment to phosphorus.

Formation of Alkyl Bromide and Dibromophosphite

As the bromide ion displaces the phosphite ester, an alkyl bromide is formed. The byproduct is a stabilized dibromophosphite compound.

Key concepts

Primary Alcohol Reaction

Primary alcohols are organic compounds that contain a hydroxyl group \((-OH)\) attached to a primary carbon atom, which is a carbon attached to only one other carbon. The reaction of primary alcohols often starts with the activation of the alcohol's hydroxyl group, making it a better leaving group for further chemical reactions. In the reaction with phosphorus tribromide \((PBr_3)\), a primary alcohol is typically transformed into an alkyl bromide.

This transformation is crucial because it converts an easily hydroxylated molecule into a halide, which is more reactive and useful in organic synthesis. In the presence of a weak base like pyridine, the primary alcohol does not deprotonate immediately, meaning the reaction proceeds with the hydroxyl group intact, prepared for subsequent steps.

Phosphorus Tribromide Mechanism

Phosphorus tribromide \((PBr_3)\) plays a significant role in converting a primary alcohol into an alkyl bromide by participating in a mechanism involving the formation of a phosphite ester. The phosphorus atom in \(PBr_3\) is electrophilic, meaning it is electron-deficient and can accept electron density from the lone pair on the oxygen atom in the alcohol.

When the lone pair attacks the phosphorus atom, a phosphite ester intermediate is formed. This intermediate is crucial as it increases the leaving group's potential. Additionally, this process releases a bromide ion which acts as a nucleophile in the subsequent reaction step, ensuring the overall conversion from alcohol to alkyl bromide.

Nucleophilic Substitution

Nucleophilic substitution is a fundamental type of reaction where a nucleophile, an electron-rich species, replaces a leaving group on a carbon atom. In this reaction mechanism, the bromide ion released from the phosphorus tribromide serves as the nucleophile.

The phosphite ester group, which was formed in the prior step, makes the carbon atom bonded to the oxygen more susceptible to nucleophilic attack. The bromide ion then attacks this carbon, displacing the phosphite ester and attaching to the carbon to form the desired product.

This substitution is a single, concerted step where bonds are broken and formed simultaneously, making it part of the classic \(S_N2\) mechanism common in primary carbon centers due to their lesser steric hindrance. This mechanism ensures efficient conversion of alcohols into alkyl bromides.

Alkyl Bromide Formation

The formation of alkyl bromides from primary alcohols via phosphorus tribromide and nucleophilic substitution has a strategic importance in organic chemistry. Alkyl bromides are versatile intermediates used in various synthesis reactions, including forming carbon-carbon bonds through reactions such as Grignard.

After the nucleophilic substitution occurs, the end product is a stable alkyl bromide and a dibromophosphite byproduct. Alkyl bromides are considerably more reactive compared to alcohols, facilitating further functional modifications. The entire sequence provides a reliable pathway for preparing versatile and reactive molecules for complex synthetic transformations in both laboratory and industrial settings.