Nucleophilic Acyl Substitution Reaction Mechanism - Carboxylic Acid Derivatives, Organic Chemistry

This paragraph discusses nucleophilic aromatic substitution reactions, focusing on acid chlorides reacting with hydroxide and water. The reaction mechanisms are explored, highlighting the formation of a tetrahedral intermediate and the subsequent departure of the chloride as the leaving group. The hydroxide's stronger basicity compared to the chloride is emphasized, leading to the formation of a carboxylic acid or a carboxylate ion under basic conditions. The paragraph also contrasts this with the reaction of water as a nucleophile, resulting in the formation of a carboxylic acid, and the reaction with methanol to produce an ester, with HCl as a side product.

The second paragraph elaborates on the reactivity of acid chlorides, noting that they do not require an acid catalyst due to the good leaving group properties of the chloride. The mechanism of ester formation with alcohols, such as methanol, is described, detailing the nucleophilic attack by the oxygen of the alcohol on the carbonyl carbon. The paragraph also provides examples of predicting products from reactions between acid chlorides and various alcohols, resulting in esters with different carbon chain lengths.

This section delves into the reactions of acid chlorides with amines, leading to the formation of amides. The mechanism involves the nucleophilic attack of the amine on the carbonyl carbon, followed by the departure of the chloride ion. The paragraph challenges the reader to predict the major products of such reactions and provides a mechanism for the conversion of an amide into a carboxylate ion and ammonia under basic conditions, facilitated by heat.

The fourth paragraph examines the hydrolysis of esters and amides under both acidic and basic conditions. The hydrolysis of esters under basic conditions results in the formation of a carboxylate ion and an alcohol, while under acidic conditions, it yields a carboxylic acid. The paragraph uses resonance structures to explain the reactivity of different oxygen atoms in the ester hydrolysis process and provides a detailed mechanism for the conversion of an ester to a carboxylic acid in the presence of an acid catalyst.

This section focuses on the acid-catalyzed hydrolysis of esters, explaining the need for an acid catalyst and heat to speed up the reaction. The mechanism involves the protonation of the ester, followed by the nucleophilic attack of water, leading to the cleavage of the ester bond and the formation of a carboxylic acid and an alcohol. The paragraph provides examples of predicting products from the hydrolysis of various esters under acidic conditions.

The sixth paragraph discusses the hydrolysis of amides into carboxylate ions and ammonia under basic conditions, with heat as a catalyst. It also explores the reaction between acid chlorides and carboxylic acids to form anhydrides, detailing the mechanism involving the nucleophilic attack of the carboxylic acid's oxygen on the acid chloride. The paragraph concludes with a discussion on the conversion of carboxylic acids into acid chlorides using SO2, leading to the formation of anhydrides.

This section describes the formation of anhydrides from two carboxylic acids under heat, resulting in the loss of water and the creation of an anhydride. It also covers the conversion of amides to nitriles using SOCl2, detailing the mechanism involving the reaction of the amide with SO2, leading to the expulsion of chloride ions and the formation of a nitrile. The paragraph also touches on the formation of lactones from the reaction of alcohols with carboxylic acids under heat.

The final paragraph examines the reaction of cyclic amides with bases and heat, leading to the opening of the ring and the formation of a carboxylate ion and an amine. The mechanism involves the nucleophilic attack of the base on the carbonyl carbon, followed by the removal of the nitrogen atom. The paragraph also discusses the conversion of amides to nitriles using SO2, detailing the mechanism and the driving force provided by the evolution of gas molecules.