CARBOXYLIC ACIDS

CARBOXYLIC ACIDS and their derivatives Carboxylic acid anhydride Carboxylic acid ester Carboxylic acid R = alkyl cycloalkyl alkenyl alkynyl aromatic ring Carboxylic acid chloride Carboxylic acid amide Nitrile

CARBOXYLIC GROUP ELECTRONIC STRUCTURE Lone-pair electrons Acidic hydrogen π-bond Lone-pair electrons Hydrocarbon framework

CARBOXYLIC GROUP THREE-DIMENSIONAL SHAPE sp2 sp3 Acetic acid - model sp3 sp2 C-C 1.52 Å C=O 1.25 Å C-OH 1.31 Å

CARBOXYLIC ACIDS – various sites of reactivity Lewis basicity (greater) (nucleophilic centre) Lewis basicity (lesser) (nucleophilic centre) α-hydrogen chemistry Brőnsted acidity Lewis acidity (electrophilic centre)

COMMON CARBOXYLIC ACIDS Aliphatic acids formic acid butyric acid acetic acid valeric acid pivalic acid propionic acid

COMMON CARBOXYLIC ACIDS Unsaturated acids acrylic acid propiolic acid crotonic acid fumaric acid trans maleic acid methacrylic acid cis

COMMON CARBOXYLIC ACIDS Dicarboxylic acids oxalic acid glutaric acid malonic acid adipic acid succinic acid

COMMON CARBOXYLIC ACIDS Aromatic acids benzoic acid phthalic acid benzoic acid

Physical constants of some CARBOXYLIC ACIDS

Carboxylic acids form dimers by strong Hydrogen Bonding Hence they have high boiling points

Dissociation of carboxylic acid vs alcohol Equivalent resonance structures: negative charge always on O Unstabilized alkoxide anion

Dissociation of carboxylic acid vs alcohol Resonance stabilization ENERGY Alkoxide anion Resonance stabilization Carboxylate anion alcohol acid REACTION PROGRESS

Which will be more acidic? Acidity of carboxylic proton vs -proton in ketone Carboxylic group Which will be more acidic? Ketone

Both anions are resonance stabilized

Acidity of carboxylic proton vs -proton in ketone Carboxylic acids: equivalent resonance structures: negative charge always on O Ketones: not equivalent resonance structures: negative charge on O or on C!

Compare acetic acid, pKa = 4.75, with acetone, pKa = 19.3!!!

EVIDENCE FOR RESONANCE OF CARBOXYLATE ANION formic acid sodium formate 1.27 Å 1.20 Å 1.34 Å 1.27 Å formic acid sodium formate

ACIDITY OF SOME CARBOXYLIC ACIDS Structure Name pKa HCl hydrochloric acid -7 F3CCOOH trifluoroacetic acid (TFA) 0.23 Cl3CCOOH trichloroacetic acid 0.64 Cl2CHCOOH dichloroacetic acid 1.26 FCH2COOH fluoroacetic acid 2.59 ClCH2COOH chloroacetic acid 2.85 BrCH2COOH bromoacetic acid 2.89 ICH2COOH iodoacetic acid 3.12 HCOOH formic acid 3.75 HOCH2COOH glycolic acid 3.83 ClCH2CH2COOH 3-chloropropanoic acid 3.98 C6H5COOH benzoic acid 4.19 H2C=CHCOOH acrylic acid 4.25 C6H5CH2COOH phenylacetic acid 4.31 CH3COOH acetic acid 4.72 CH3CH2COOH propanoic acid 4.87 CH3CH2OH ethanol 16 Stronger acid Weaker acid

SUBSTITUENT EFFECT ON ACIDITY acetic acid chloroacetic acid dichloroacetic acid trichloroacetic acid pKa = 4.72 pKa = 2.85 pKa = 1.26 pKa = 0.64 Weaker acid Stronger acid

SUBSTITUENT EFFECT ON ACIDITY Electron Withdrawing Group stabilizes carboxylate anion and strenghtens acidity Electron Donating Group destabilizes carboxylate anion and weakens acidity

SUBSTITUENT EFFECTS ON ACIDITY Explain the difference in pKa values. The greater the distance (number of bonds) between an electron-withdrawing group (here chlorine) and the point of ionization, the less effect an electron-withdrawing group has.

SUBSTITUENT EFFECT ON ACIDITY Dicarboxylic acids pKa1 pKa2 Oxalic acid 1.2 4.2 Succinic acid 4.2 5.6 Adipic acid 4.4 4.4

SUBSTITUENT EFFECT ON ACIDITY Para-substituted benzoic acids pKa = 4.46 pKa = 4.19 pKa = 3.41 EDG – destabilizes carboxylate anion, decreases acidity EWG – stabilizes carboxylate anion, increases acidity Weaker acid Stronger acid

SUBSTITUENT EFFECT ON ACIDITY Para-substituted benzoic acids Y pKa -OH 4.55 -OCH3 4.46 -CH3 4.34 -H 4.19 -Br 3.96 -Cl 3.96 -CHO 3.75 -CN 3.55 -NO2 3.41 EDG (activating ring in electrophilic substitution) EWG (deactivating ring in electrophilic substitution) Acidity

Preparation of carboxylic acids (Industrial methods)

Preparation of carboxylic acids Laboratory methods 1. Oxidation of alkylbenzenes, primary alcohols, aldehydes 88% yield 93% yield

85% yield

2. Hydrolysis of nitriles 3. Carboxylation of Grignard reagents 73% yield

General reactions of carboxylic acids Deprotonation Decarboxylation Reduction 16 October 2017 α-Substitution Nucleophilic acyl substitution

Decarboxylation Hunsdiecker reaction 93% yield 100% yield

Deprotonation Salt formation in alkaline solutions: Na2CO3 can also be used

Deprotonation Salt formation with ammonia (NH3) or amines (RNH2, R2NH, R3N): Proton transfer from carboxyl oxygen to amine nitrogen

Reduction 87% yield 94% yield

-Substitution -Halogenation of carboxylic acids – Hell, Volhard, Zelinskii reaction 90% yield

Mechanism of -Halogenation

Nucleophilic acyl substitution Net effect – replacing of hydroxyl group with nuclephile -OH is called leaving group

Fischer esterification as nucleophilic acyl substitution Alcohol reactivity order: primary > secondary > tertiary R E A C T I V I T Y

Fischer esterification as nucleophilic acyl substitution (mechanism) The full mechanism for Fischer esterification as well as for the reverse reaction, acid-catalyzed hydrolysis of an ester to a carboxylic acid.