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Organic Chemistry - Chapter 20: Carboxylic Acids

Introduction to Carboxylic Acids

  • Carboxylic acids feature a carbonyl group (C=O) with a hydroxyl group (-OH) attached to the same carbon.
  • The carboxyl group is typically written as -COOH.
  • Aliphatic acids have an alkyl group bonded to the -COOH group.
  • Aromatic acids have an aryl group bonded to the -COOH group.
  • Fatty acids are long-chain aliphatic acids.

Nomenclature of Carboxylic Acids

Common Names

  • Many aliphatic acids have historical common names.
  • Substituent positions on the chain are indicated using Greek letters, starting with the carbon adjacent to the carboxyl carbon.

IUPAC Names

  • To derive the IUPAC name, remove the final "-e" from the corresponding alkane name and add the ending "-oic acid".
  • The carbon of the carboxyl group is designated as carbon number 1.

Unsaturated Acids

  • Unsaturated carboxylic acids are named by removing the final "-e" from the alkene name and adding "-oic acid."
  • Numbering starts at the carboxyl group, and the location of the double bond is specified.
  • Stereochemistry (E or Z) around the double bond should be indicated.

Aromatic Acids

  • Aromatic acids are named as derivatives of benzoic acid.
  • The prefixes ortho-, meta-, and para- are used to indicate the position of a second substituent.
  • Numbers are used to specify substituent locations when there are more than two substituents.

Dicarboxylic Acids

  • Aliphatic diacids often go by their common names, with Greek letters indicating the carbon atoms next to the carboxyl groups.
  • For IUPAC names, number the carbon chain from the end closest to a substituent.

Names and Physical Properties of Carboxylic Acids

  • The table lists various carboxylic acids with their IUPAC names, common names, formulas, melting points (°C), boiling points (°C), and solubility in water (g/100 g H2O).
  • Examples include methanoic acid (formic acid), ethanoic acid (acetic acid), propanoic acid (propionic acid), and others with varying carbon chain lengths and substituents.
  • Solubility in water generally decreases as the carbon chain length increases.

Structure and Physical Properties of Carboxylic Acids

Structure of the Carboxyl Group

  • The carbonyl carbon in a carboxyl group is sp^2 hybridized and planar with nearly trigonal bond angles.
  • The O-H bond lies in the same plane as the C=O bond, in an eclipsed conformation.
  • The sp^3 hybridized oxygen exhibits a C-O-H angle of approximately 106°.

Resonance Structures of Formic Acid

  • One of the unshared electron pairs on the hydroxyl oxygen atom is delocalized into the electrophilic pi system of the carbonyl group.
  • This delocalization requires the O-H bond to be eclipsed with the C=O bond to allow overlap of the p orbital with a lone pair orbital on the oxygen.

Boiling Points

  • Carboxylic acids have significantly higher boiling points compared to alcohols, ketones, and aldehydes with similar molecular weights.
  • These high boiling points are attributed to the formation of stable, hydrogen-bonded dimers.

Melting Points

  • Aliphatic acids with more than eight carbon atoms are typically solid at room temperature.
  • The presence of double bonds, specifically cis double bonds, lowers the melting point.
    • Example:
      • Stearic acid (saturated, 18 carbons): Melting point = 72 °C
      • Oleic acid (one cis double bond, 18 carbons): Melting point = 16 °C
      • Linoleic acid (two cis double bonds, 18 carbons): Melting point = -5 °C

Solubility

  • Water solubility decreases as the carbon chain length increases.
  • Acids with more than 10 carbon atoms are nearly insoluble in water.
  • Carboxylic acids are soluble in alcohols and relatively nonpolar solvents like chloroform because the hydrogen bonds of the dimer are not disrupted by the nonpolar solvent.

Acidity of Carboxylic Acids

  • Carboxylic acids can dissociate in water to yield a proton and a carboxylate ion.
  • The equilibrium constant for this reaction is the acid-dissociation constant, K_a.
  • The acid will be mostly dissociated if the pH of the solution is higher than the pK_a of the acid.
  • Energy diagram compares acidity of alcohols (pKa = 16) and carboxylic acids (pKa = 5), illustrating greater stabilization of the carboxylate ion compared to alkoxide ions.

Acetate Ion Structure

  • Each oxygen atom in the acetate ion carries half of the negative charge due to resonance.
  • The delocalization of the negative charge across both oxygen atoms makes the acetate ion more stable than an alkoxide ion.

Substituent Effects on Acidity

  • The magnitude of a substituent's effect on acidity depends on its proximity to the carboxyl group.

Aromatic Carboxylic Acids

  • Electron-withdrawing groups enhance the acid strength, while electron-donating groups decrease the acid strength.
  • These effects are most pronounced when substituents are in the ortho and para positions.

Values of Ka and pKa for Substituted Carboxylic Acids

  • Table listing various substituted carboxylic acids with their respective Ka and pKa values.
  • This table contains acids includes trifluoroacetic acid, dichloroacetic acid, chloroacetic acid, nitroacetic acid, cyanoacetic acid, fluoroacetic acid, chloroacetic acid, and others with varying substituents.
  • The table also lists acids such as 3-chlorobutanoic acid, bromoacetic acid, iodoacetic acid, methoxyacetic acid, lactic acid, 3-chloropropanoic acid, benzoic acid, phenylacetic acid, 4-chlorobutanoic acid, acetic acid, and butanoic acid.

Salts of Carboxylic Acids

Deprotonation of Carboxylic Acids

  • Hydroxide ions completely deprotonate carboxylic acids, forming carboxylate salts.

Protonation of Carboxylic Acid Salts

  • Adding a strong acid, such as HCl, regenerates the carboxylic acid.

Naming Carboxylic Acid Salts

  • First, name the cation (e.g., sodium, potassium, etc.).
  • Then, name the anion by replacing the "-ic acid" ending with "-ate" (e.g., acetate, benzoate, etc.).

Properties of Acid Salts

  • Carboxylate salts are typically solids with no odor.
  • Carboxylate salts of Na^+, K^+, Li^+, and NH_4^+ are soluble in water.
  • Soap consists of soluble sodium salts of long-chain fatty acids.
  • Salts can be formed by the reaction of an acid with NaHCO3, which releases CO2.

Extraction of Carboxylic Acids

  • Carboxylic acids are more soluble in organic phases, while their salts are more soluble in aqueous phases.
  • Acid-base extractions can be used to move the acid between ether and aqueous phases, effectively separating it from impurities.

Spectroscopy of Carboxylic Acids

IR Bands of Carboxylic Acids

  • IR spectra of carboxylic acids exhibit two characteristic features:
    • An intense carbonyl stretching absorption at approximately 1710 cm^{-1}.
    • A broad O-H absorption in the range of 2500-3500 cm^{-1}.
  • Conjugation lowers the frequency of the C=O band.

NMR of Carboxylic Acids

  • Carboxylic acid protons are highly deshielded, absorbing between δ 10 and δ 13 ppm.
  • Protons on the α-carbon atom absorb between δ 2.0 and δ 2.5 ppm.

MS of Carboxylic Acids

  • A common fragmentation pathway involves the loss of an alkene via the McLafferty rearrangement.
  • Another common fragmentation involves cleavage of the β-γ bond, forming an alkyl radical and a resonance-stabilized cation.

Synthesis of Carboxylic Acids

  • Oxidation of primary alcohols and aldehydes using chromic acid (H2CrO4).
  • Cleavage of alkenes with hot KMnO_4 produces a carboxylic acid if a vinylic hydrogen is present.
  • Ozonolysis of alkynes.
  • Alkyl benzenes are oxidized to benzoic acid by hot KMnO_4 or hot chromic acid.

Oxidation of Primary Alcohols to Carboxylic Acids

  • Primary alcohols and aldehydes are commonly oxidized to carboxylic acids by chromic acid (H2CrO4), formed from Na2Cr2O7 and H2SO_4.
  • Potassium permanganate (KMnO_4) is occasionally used, but yields are often lower.

Cleavage of Alkenes Using KMnO_4

  • Warm, concentrated permanganate solutions oxidize glycols, cleaving the central C=C bond.
  • Depending on the substitution of the original double bond, ketones or acids may result.

Alkyne Cleavage Using Ozone or KMnO_4

  • Ozonolysis or vigorous permanganate oxidation cleaves triple bonds in alkynes to yield carboxylic acids.

Side-Chain Oxidation of Alkylbenzenes

  • Alkylbenzenes are oxidized to benzoic acids using Na2Cr2O7 in H2SO4 with heat, or KMnO4 in water with heat.

Carboxylation of Grignard Reagents

  • Grignard reagents react with CO_2 to produce, after protonation, a carboxylic acid.
  • This reaction, referred to as “CO_2 insertion,” increases the number of carbons in the molecule by one.

Hydrolysis of Nitriles

  • Acidic or basic hydrolysis of a nitrile (-CN) yields a carboxylic acid.
  • The overall reaction, starting from an alkyl halide, adds an extra carbon to the molecule.

Reactions of Carboxylic Acids and Derivatives; Nucleophilic Acyl Substitution

  • The group bonded to the acyl carbon determines the class of compound:
    • -OH: Carboxylic acid
    • -Cl: Acid chloride
    • -OR': Ester
    • -NH2: Amide
  • These compounds interconvert via nucleophilic acyl substitution.

Nucleophilic Acyl Substitution

  • Carboxylic acids react by nucleophilic acyl substitution, where one nucleophile replaces another on the acyl (C=O) carbon atom.

Condensation of Acids with Alcohols: The Fischer Esterification

  • Reaction of a carboxylic acid with an alcohol under acidic conditions produces an ester.
  • The reaction is an equilibrium; the yield of ester is not high.
  • To drive the equilibrium toward the formation of products, use a large excess of alcohol.

Mechanism of the Fischer Esterification

Step 1:

  • The carbonyl oxygen is protonated to activate the carbon toward nucleophilic attack.
  • The alcohol attacks the carbonyl carbon.
  • Deprotonation of the intermediate produces the ester hydrate.

Step 2:

  • Protonation of one of the hydroxide groups creates a good leaving group.
  • Water leaves.
  • Deprotonation of the intermediate produces the ester.

Esterification Using Diazomethane

  • Carboxylic acids are converted to their methyl esters by adding an ether solution of diazomethane.
  • This reaction typically produces quantitative yields of ester.
  • Diazomethane is a very toxic, explosive, yellow gas.

Mechanism of Diazomethane Esterification

Step 1:

  • Proton transfer, forming a carboxylate ion and a methyldiazonium ion.

Step 2:

  • Nucleophilic attack on the methyl group displaces nitrogen.

Condensation of Acids with Amines: Direct Synthesis of Amides

  • The initial reaction of a carboxylic acid with an amine gives an ammonium carboxylate salt.
  • Heating this salt to well above 100 °C drives off water and forms an amide.

Reduction of Carboxylic Acids

  • LiAlH_4 reduces carboxylic acids to primary alcohols.
  • The intermediate aldehyde reacts faster with the reducing agent than the carboxylic acid.
  • Borane can also reduce the carboxylic acid to the alcohol.

Reduction of Acid Chlorides to Aldehydes

  • Lithium aluminum tri(tert-butoxy)hydride is a weaker reducing agent than lithium aluminum hydride.
  • It reduces acid chlorides because they are strongly activated toward nucleophilic addition of a hydride ion.
  • Under these conditions, the aldehyde reduces more slowly and is easily isolated.

Alkylation of Carboxylic Acids to Form Ketones

  • A general method for making ketones involves reacting a carboxylic acid with two equivalents of an organolithium reagent.

Mechanism of Ketone Formation

  • The first equivalent of organolithium acts as a base, deprotonating the carboxylic acid.
  • The second equivalent adds to the carbonyl.
  • Hydrolysis forms the hydrate of the ketone, which converts to the ketone.

Synthesis and Use of Acid Chlorides

  • The best reagents for converting carboxylic acids to acid chlorides are thionyl chloride (SOCl2) and oxalyl chloride (COCl2).
  • These reagents form gaseous by-products that do not contaminate the product.

Effective Esterification of a Carboxylic Acid

  • Esterification of an acyl chloride is more efficient than the Fischer esterification.

Amide Synthesis

  • Ammonia and amines react with acid chlorides to give amides.
  • NaOH, pyridine, or a second equivalent of amine is used to neutralize the HCl produced to prevent amine protonation.