Carboxylic Acids (RCO2H) and Nitriles Carboxylic Acids

Naming Carboxylic Acids and Nitriles Carboxylic Acids Simple carboxylic acids derived from open-chain alkanes are systematically named by replacing the terminal e of the corresponding alkane name with oic acid -CO2H carbon is numbered C1

-CO2H group bonded to a ring are named using the suffix carboxylic acid CO2H carbon is attached to C1 in this system and is not itself numbered As a substituent, the CO2H group is called a carboxyl group Nitriles RCN Compounds containing the -CN functional group Simple open-chain nitriles are named by adding nitrile as a suffix to the alkane name with the nitrile carbon numbered C1

Can also be named as derivatives of carboxylic acids by replacing the -ic acid or oic acid ending with onitrile, or by replacing the carboxylic acid ending with carbonitrile. The nitrile carbon atom is attached to C1 but is not itself numbered

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If another carboxylic acid derivate is present in the same molecule, the prefix cyano is used for the CN group

Structure and Properties of Carboxylic Acids Carboxyl carbon is sp2 hybridized Planar with C-C=O and O=C-O Bond angles approx. 120 Strongly associated because of hydrogenbonding has an effect on boiling points making carboxylic acids much higher boiling than the corresponding alcohols Most exist as cyclic dimers held together by 2 hydrogen bonds

Acetic acid Ka = 1.75x10-5 pKa = 4.76 Weaker than mineral acids Stronger acids than alcohols and phenols alcohols dissociate to give an alkoxide ion, in which the negative charge is localized on a single electronegative atom. A carboxylic acid gives carboxylate ion, in which the negative charge is delocalized over 2 equivalent oxygen atoms. In resonance terms, a carboxylate ion is a stabilized resonance hybrid of 2 equivalent structures. A carboxylate ion is lower in energy than an alkoxide ion and more favored in the dissociation equilibrium

Acidic react with bases such as NaOH and NaHCO3 to give metal carboxylate salts (RCO2M +) More than 6 carbons slightly soluble with water Alkali metal salts are often highly water-soluble

Dissociate slightly in dilute aqueous solution to give H3O+ and the corresponding carboxylate anions (RCO2-)

Biologic Acids and the Henderson-Hasselbach Equation In acidic solution (low pH) carboxylic acid is completely undissociated and exists entirely as RCO2H In basic solution (high pH) carboxylic acid is completely dissociated and exists entirely as RCO2At Physiologic pH (pH = 7.3) that exists inside cells buffered to almost neutral carboxylic acids are almost entirely dissociated

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When pH = pKa the 2 forms HA and A- are present in equal amounts because log 1 = 0

Substituent Effects on Acidity Any factor that stabilizes the carboxylate anion relative to undissociated carboxylic acid will drive the equilibrium toward increased dissociation and result in increased acidity

Inductive effects operate through bonds and are dependent on distance, the effect of halogen substitution decreases as the substituent moves farther from the carboxyl

Preparing Carboxylic Acids Oxidation of Aromatic Compounds Benzene is inert to strong oxidizing agents e.g. KMnO4 and Na2Cr2O7 that will cleave alkene carbon-carbon bonds but its presence has a dramatic effect on alkyl side chains Alkyl side chains react rapidly with oxidizing agents and are converted into carboxyl groups (-CO2H) Net effect: conversion of an alkylbenzene into a benzoic acid (Ar-R Ar-CO2H)

Aromatic rings with electron-donating groups are activated toward further electrophilic substitution, and aromatic rings with electron-withdrawing groups are deactivated

Involves reaction of C-H bonds at the position next to the aromatic ring to form intermediate benzylic radicals tert-Butylbenzene is inert because it has no benzylic hydrogens

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Oxidation of Alcohols Primary alcohols are oxidized to either aldehydes or carboxylic acids by CrO3 or Na2Cr2O7 Primary alcohols are directly oxidized to carboxylic acids Aldehyde is involved as an intermediate but cant be isolated because it is oxidized too rapidly

SN2 reaction of a primary or secondary alkyl halide with CN-, the two-step sequence of cyanide displacement followed by nitrile hydrolysis RBr RCN RCO2H Product acid has one more carbon than the starting alkyl halide

Oxidation of Aldehydes and Ketones Aldehydes are easily oxidized to yield carboxylic acids Ketones are inert toward oxidation Aldehydes have a CHO proton that can be abstracted during oxidation, but ketones do not.

KMnO4, CrO3, and hot HNO3 convert aldehydes into carboxylic acids

Carboxylation of Grignard Reagents Reaction of a Grignard reagent with CO2 to yield a metal carboxylate, followed by protonation to give the carboxylic acid Carried out by bubbling a steam of dry CO2 gas through a solution of the Grignard reagent (Carboxylation) Organomagnesium halide adds to a C=O bond of carbon dioxide in a typical nucleophilic carbonyl addition reaction, and protonation of the carboxylate by addition of aqueous HCl in a separate step then gives the free carboxylic acid

The oxidation occurs rapidly at room temperature Aldehyde oxidations occur through intermediate 1,1-diols or hydrates which are formed by a reversible nucleophilic addition of water to the carbonyl group. The hydrate reacts like any typical primary or secondary alcohol and is oxidized to a carbonyl compound

Ketones undergo a slow cleavage reaction of the C-C bond next to the carbonyl group when treated with hot alkaline KMnO4

Hydrolysis of Nitriles

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Reactions of Carboxylic Acids: An Overview Like alcohols, carboxylic acids can be deprotonated to give anions, which are good nucleophiles in SN2 reactions Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group

Reduction by treatment of the acids with LiAlH4 Chemistry of Nitriles Nitriles and carboxylic acids both have a carbon atom with 3 bonds to an electronegative atom and both contain a bond Both are electrophiles and both undergo nucleophilic addition reactions Reaction occurs in either basic or acidic aqueous solution Further hydrolysis of the amide intermediate takes place by a nucleophilic addition of hydroxide ion to the amide carbonyl group which yields a tetrahedral alkoxide ion Expulsion of amide ion (NH2-) as leaving group gives the carboxylate ion, thereby giving the reaction towards products. Subsequent acidification in a separate step yields the carboxylic acid

Hydrolysis: Conversion of Nitriles Hydrolysis to yield an amide and then a carboxylic acid plus ammonia or an amine

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