Carboxylic acids and their derivatives

• All carboxylic acid derivatives have the formula, ROX, where X atom is more electronegative than C
• The reactivity of the carbonyl group lies in its polarity
• The negative atom expelled in the initial nucleophilic addition reaction depends on their relative basicity's and ability to act as a leaving group.
• The weaker the base, the better it is as a leaving group, this can be seen by looking at the peas of the conjugate acids
• For a nucleophilic acyl substitutions to take place, X- should be a weaker base than Y-, so Y will replace X in the product

  Y = atom being added

  X = atom already on molecule
• Basicity is correlated with group ability and relative reactivity, weaker the base attacked to C=O, easier for the reaction to take place. Less basic the substituent, the more reactive the compound
• Weaker bases are more electronegative and are better at withdrawing electrons inductively from the carbonyl C atom, which makes it more delta positive and increases it s susceptibility to nucleophilic attack
• The weaker the basicity of Y, the smaller the resonance contribution from X - greater the basicity, the greater this contribution
• Greater the delocalisation, the less reactive the carbonyl group, so a reduced delta positive charge
• Acid chloride are the most reactive of the carboxylic acid derivatives, so undergo the most reactions. Acid chlorides readily react with nucleophiles to form nucleophilic substitution products with HCl formed as a by-product
• Acid chlorides react with RONu to give anhydrides, carboxylic acids and esters
• For an acyl chloride reaction with ammonia and primary and secondary amines, two equivalents of the amine are always required as one is used to form the amide and the other is used as a base and to neutralise the HCl that is formed
• Acid anhydrides are less reactive than acid chlorides, but still react with most nucleophiles to form substitution products
• In reactions of acid anhydrides, the nucleophilic attack occurs at one carbonyl group, second carbonyl group becomes part of the leaving group
• Acid anhydrides will not form acid chlorides as RCOO- is a stronger case so will be a worse leaving group than Cl-
• Acid anhydrides can be used to make all other acyl derivatives
• Industrially, anhydrous are used to prepare esters and amides, it is safer to use anhydrides than acyl chlorides
• Carboxylic acids are strongly polar due to C=O and O-H bonds. They exhibit intermolecular H bonding which forms dimers that are held together by two H bonds
• Carboxylic acids are stronger acids with pKa 4-5, and can deprotonate to form the carboxylate anion more rapidly than attack at the carbonyl group
• Conversion of carboxylic acids into acid chlorides cannot take place directly using Cl- as the nucleophile as it is a weaker base than the leaving group - instead, reagent thionyl chloride is used which converts -OH into a better leaving group which Cl- can displace
• Conversion of carboxylic acids into acid anhydrides is hard, so dicarboxylic acids are converted to cyclic anhydrides by heating to high temperatures
• Fischer esterification shows the treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst to form an ester - equilibrium reaction driven to completion by removing the water as it is formed
• Conversion of carboxylic acids into amides using a direct addition of an amine is not good as the basic amine with deprotonate the carboxylic acid
• Conversion of esters into carboxylic acids is done by hydrolysis and is converted with water using either acid or basic conditions
• Esters are reduced by strong reducing agents to either aldehydes or alcohols depending on the reducing agent used
• Esters with reducing agent diisobutylaluminium hydride forms aldehydes
• Esters with reducing agent lithium aluminium hydride forms alcohols
• Esters can react with organometallic reagents to from ketones or tertiary alcohols
• Amides are the least reactive so have the worst leaving group of all the carboxylic acid derivatives. Under harsh conditions, amides are hydrolysed in either acid or base to form carboxylic acids and amines
• Nitriles are easily prepared by nucleophilic Sn2 substitution reactions of alkyl halides
• Nitriles are polarised like carbonyl groups but do not undergo nucleophilic substitution as they do not have a leaving group, so undergo nucleophilic addition