Carboxylic Acids and Derivatives

Naming Carboxylic Acids Starting materials for acyl derivatives (esters, amides, and acid chlorides) Abundant in nature from oxidation of aldehydes and alcohols in metabolism Carboxylic Acids, RCO 2 H If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid The carboxyl carbon atom is C1

Alternative Names Compounds with  CO 2 H bonded to a ring are named using the suffix -carboxylic acid The CO 2 H carbon is not itself numbered in this system Use common names for formic acid (HCOOH) and acetic acid (CH 3 COOH)

Common names

Structure and Physical Properties of Carboxylic Acids Carboxyl carbon sp 2 hybridized: carboxylic acid groups are planar with C–C=O and O=C–O bond angles of approximately 120° Carboxylic acids form hydrogen bonds, existing as cyclic dimers held together by two hydrogen bonds Strong hydrogen bonding causes much higher boiling points than the corresponding alcohols

Dissociation of Carboxylic Acids Carboxylic acids are proton donors toward weak and strong bases, producing metal carboxylate salts, RCO 2  + M Carboxylic acids with more than six carbons are only slightly soluble in water, but their conjugate base salts are water-soluble Sodium Carboxylate

Acidity Compared to Alcohols Carboxylic acids are better proton donors than are alcohols (The pK a of ethanol is ~16, compared to ~5 for acetic acid) In an alkoxide ion, the negative charge is localized on oxygen while in a carboxylate ion the negative charge is delocalized over two equivalent oxygen atoms, giving resonance stabilization

Substituent Effects on Acidity Electronegative substituents promote formation of the carboxylate ion

Substituent Effects in Substituted Benzoic Acids

Preparation of Carboxylic Acids Oxidation of a primary alcohol or an aldehyde with CrO 3 in aqueous acid

From alkyl benzene Oxidation of a substituted alkylbenzene with KMnO 4 gives a substituted benzoic acid 1° and 2° alkyl groups can be oxidized, but tertiary groups are not

From Alkenes Oxidative cleavage of an alkene with KMnO 4 gives a carboxylic acid if the alkene has at least one vinylic hydrogen

Hydrolysis of Nitriles Hot acid yields carboxylic acids Conversion of an alkyl halide to a nitrile (with cyanide ion) followed by hydrolysis produces a carboxylic acid with one more carbon (RBr  RC  N  RCO 2 H) Best with primary or secondary halides because tertiary alkyl halides are sterically hindered

Carboxylation of Grignard Reagents Grignard reagents react with dry CO 2 to yield a metal carboxylate Limited to alkyl halides that can form Grignard reagents

Mechanism of Grignard Carboxylation The organomagnesium halide adds to C=O of carbon dioxide Protonation by addition of aqueous HCl in a separate step gives the free carboxylic acid

Reactions of Carboxylic Acids: An Overview Carboxylic acids transfer a proton to a base to give anions, which are good nucleophiles in S N 2 reactions Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group In addition, carboxylic acids undergo other reactions characteristic of neither alcohols nor ketones

Reduction of Carboxylic Acids Reduced by LiAlH 4 to yield primary alcohols The reaction is difficult and often requires heating in tetrahydrofuran solvent to go to completion

Reduction with Borane Borane in tetrahydrofuran (BH 3 /THF) converts carboxylic acids to primary alcohols selectively Preferable to LiAlH 4 because of its relative ease, safety, and specificity

19 Nucleophilic Acyl Substitution Carboxylic acid derivatives have an acyl carbon bonded to a group  Y that can leave A tetrahedral intermediate is formed and the leaving group is expelled to generate a new carbonyl compound, leading to substitution

Carboxylic acid derivatives Acyl group bonded to X, an electronegative atom or leaving group Includes: X = halide (acid halides), acyloxy (anhydrides), alkoxy (esters), amine (amides), thiolate (thioesters)

21 Naming Carboxylic Acid Derivatives Acid Halides, RCOX Derived from the carboxylic acid name by replacing the -ic acid ending with -yl or the -carboxylic acid ending with –carbonyl and specifying the halide

22 Naming Acid Anhydrides, RCO 2 COR' If symmetrical replace “acid” with “anhydride” based on the related carboxylic acid Unsymmetrical anhydrides— cite the two acids alphabetically

23 Naming Amides, RCONH 2 With unsubstituted  NH 2 group. replace -oic acid or -ic acid with -amide, or by replacing the -carboxylic acid ending with –carboxamide If the N is further substituted, identify the substituent groups (preceded by “N”) and then the parent amide

24 Naming Esters, RCO 2 R’ Name R’ and then, after a space, the carboxylic acid (RCOOH), with the “-ic acid” ending replaced by “-ate”

Name the following compounds 4-methylpentanoyl ChlorideCylopentyl 2-methylpropanoate Isopropyl Cyclopentanecarboxylate Isopropyl 2-methylpropanoate 2-Cylcohexyl Acetamide N-Methyl-4-pentenamide

26 Relative Reactivity of Carboxylic Acid Derivatives Nucleophiles react more readily with unhindered carbonyl groups More electrophilic carbonyl groups are more reactive to addition (acyl halides are most reactive, amides are least) The intermediate with the best leaving group decomposes fastest