Reactions of Carboxylic Acid Derivatives

Preparation of Carboxylic Acids

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 (C=O{\rm{C{=}O}} ) bound to one alkyl (R{-}{\rm {R}} ) fragment and one hydrogen atom, with RC(=O)H {\rm{RC({=}O)H} } or RCHO{ \rm{R{-}CHO}} 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 (C=O{\rm {C{=}O}}) bound to two alkyl (R{-}{\rm {R}}) fragments (which can be the same, R and R, or different, R and R′) with RC(=O)R{\rm{RC({=}O)R}}' or RCOR′ stoichiometry. Tertiary alcohols cannot be oxidized because an oxidized tertiary alcohol would have five bonds to carbon, which violates the octet rule.

Oxidation of Primary Alcohol and Aldehyde to Form Carboxylic Acid

1-pentanol (C5H11OH) is oxidized to a carboxylic acid by using chromic acid or reagent combinations that generate chromic acid. The first oxidation product is pentanal (C5H10O), and this is oxidized once more to form pentanoic acid (C5H10O2).
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 (C=O{\rm {C{=}O}}) bound to the same oxygen atom with (RCO)2O stoichiometry.

Formation of Carboxylic Acids via Ozonolysis of an Alkene

Ozonolysis can be used to break a five-carbon alkene into a four-carbon aldehyde and a one-carbon aldehyde. These can be further oxidized to their respective carboxylic acids (or CO2).
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.

Oxidation of Benzylic Carbons

Carbons with sp3 hybridization that are adjacent to the benzene ring are called benzylic carbons. During oxidation, the bonds in the alkyl chain past the benzylic carbon are broken and then oxidized. The product substituent groups contain two fewer carbons than the alkyl chains.
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 (OH {-}{\rm {OH}}) and a cyano group (CN{\rm{C{\equiv}N}}) 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.

Generic Structure of a Cyanohydrin

The carbon atom bonds to a cyano group (CN{\rm{C{\equiv}N}}) and a hydroxyl group (OH{-}{\rm{OH}}). Cyanohydrins can be used to produce carboxylic acids.

Hydrolysis of a Cyanohydrin to Form Carboxylic Acid

The cyanohydrin reacts with water to form a carboxylic acid on the carbon that was bonded to the cyano group.
Finally, carboxylic acids are prepared by the carbonation of Grignard reagents. A Grignard reagent has the formula RMgX{\rm{R{-}MgX}}, where the halogen may be Cl{-}{\rm{Cl}} , Br{-}\rm{Br} , or I{-}{\rm{I}} . 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.

Carbonation of a Grignard Reagent

Grignard reactions are used to add carbons to a structure in the form of a carboxylic acid functional group.