Carboxylic acids are prepared in a variety of ways, including the oxidation of primary alcohols and aldehydes, the ozonolysis of alkenes and alkynes, the oxidation of benzylic carbons, the hydrolysis of nitriles, and the carbonation of the Grignard reagent.
Carboxylic acids are prepared by the oxidation of primary alcohols, which have a hydroxyl group bound to the primary carbon, using chromium and other oxidizing agents. Pyridinium chlorochromate (PCC), Swern, and Dess-Martin periodinane (DMP) are oxidizing reagents that are used to oxidize the primary alcohol to an aldehyde. An aldehyde is an organic compound that contains a carbonyl group () bound to one alkyl () fragment and one hydrogen atom, with or stoichiometry. When using strong oxidizing agents, such as potassium permanganate, the oxidation will continue to a carboxylic acid unless this process is prevented. To prevent further oxidation, an excess of the primary alcohol can sometimes be used to limit the reaction, or the aldehyde is distilled from the mixture immediately after its formation. The oxidation of secondary alcohols generally results in a ketone. A ketone is an organic compound that contains a carbonyl group () bound to two alkyl () fragments (which can be the same, R and R, or different, R and R′) with or RCOR′ stoichiometry. Tertiary alcohols cannot be oxidized because an oxidized tertiary alcohol would have five bonds to carbon, which violates the octet rule.
Carboxylic acids are also prepared via the ozonolysis of alkenes or alkynes followed by oxidative workup. Ozonolysis is the cleavage of an alkene, alkyne, or azo group with ozone. In this process, the double bond of an alkene is cleaved to form two aldehydes, with the carbonyl carbon in each originating from either side of the double bond. This is then oxidized to form the corresponding carboxylic acids. In the ozonolysis of an alkyne, the process is different. The triple bond breaks to form an acid anhydride that forms two carboxylic acids in the presence of water (or a carboxylic acid and a carbon dioxide with terminal alkynes). An acid anhydride is an organic compound that contains two carbonyl groups () bound to the same oxygen atom with (RCO)2O stoichiometry.
Oxidation of Primary Alcohol and Aldehyde to Form Carboxylic Acid
Carboxylic acids are also prepared via oxidation of benzylic carbons as long as there is at least one hydrogen on the benzylic position. The hydrogen atom is necessary for the elimination step of the oxidation mechanism. The benzylic carbon is the carbon that is adjacent to a benzene ring. The structure cleaves at the benzylic carbon, and any carbons past a benzylic carbon in the chain will not be part of the final carboxylic acid structure.
Formation of Carboxylic Acids via Ozonolysis of an Alkene
Carboxylic acids are also prepared by the hydrolysis of nitriles. A nitrile is an organic compound that has a carbon triple bonded to a nitrogen with RCN stoichiometry; it is also called a cyano group. Hydrolysis is the addition of water to a molecule to cause a covalent bond to break. An example of a nitrile that can undergo hydrolysis to form a carboxylic acid is a cyanohydrin. A cyanohydrin is a compound that contains a carbon that is bonded to a hydroxyl group () and a cyano group () on the same carbon. The nitrogen from the cyanohydrin is protonated and creates a strong electrophile at the nitrile carbon. Water reacts with this through several steps to result in the formation of a carboxylic acid.
Oxidation of Benzylic Carbons
Generic Structure of a Cyanohydrin
Finally, carboxylic acids are prepared by the carbonation of Grignard reagents. A Grignard reagent has the formula , where the halogen may be , , or . Carbonation is a reaction that results in the addition of a carbon to a structure. Grignard reagents are compounds containing magnesium and alkyl halides that act as nucleophiles (electron donating) in reactions. The charged carbon atom in the Grignard reagent attacks the electrophilic (electron accepting) of carbon dioxide and forms a complex intermediate. This results in a new carbon-carbon bond. In the presence of an acid workup, the carboxylate ion becomes a carboxylic acid.