Carboxylic acids and their derivatives

Carboxylic acid structure Formula -COOH Oxygen atoms not joined together. General formula when rest of structure is an alkyl group R-COOH. C O H Carboxyl group

Structure Two functional groups adjacent to each other R C O O-H -I effect C=O and –OH groups modify each other and shows different properties.

Structure of Carboxyl Carbon is sp2 hybridized. Bond angles are close to 120. O-H eclipsed with C=O, to get overlap of  orbital with orbital of lone pair on oxygen. =>

Possible reactions O R C H Carbonyl group property Acidic property Decarboxylation Alkanolic property

Acidity O R C H Greater polarization of this bond extra +ve Polarization of this bond is increased, O-H bond is weakened. (Acidic)

Acidity R C O- O R C O O- .. -ve charge is spreaded over the –C=O group and stabilize the anion RCOO- R C O O- ..

Acid strength RCOOH  RCOO- + H+ All are weak acids, Acid pKa HCOOH 3.8 CH3COOH 4.8 CH3CH2COOH 4.9 All are weak acids, <1% ionized in water

Substituent Effects on Acidity => pKa = 4.46 pKa = 4.19 pKa = 3.47 pKa = 3.41 pKa = 2.16

Naming carboxylic acids Alkanes CH4 methane CH3 -CH3 ethane CH3-CH2-CH3 propane. CH3-CH(CH3)-CH2- CH3 2-methylbutane Carboxylic acids H-COOH methanoic acid CH3 -COOH ethanoic acid CH3-CH2-COOH propanoic acid CH3-CH(CH3)-CH2-COOH 3-methylbutanoic acid

Naming more complex examples Two carboxylic acid groups -dioic Carboxyl group can be attached to a benzene ring eg benzenecarboxylic acid. COOH COOH ethanedioic acid benzene-1,4-dicarboxylic acid COOH COOH CH 2 benzenecarboxylic acid (benzoic acid) propanedioic acid

Naming practise. Name these structures Butanoic acid Octanoic acid Pentanedioic acid Benzene-1,2-dicarboxylic acid

2-Chloropentanoic acid 2-Methylpropanoic acid a-Methylpropionic acid Isobutyric acid 4-Methylpentanoic acid g-Methylvaleric acid Isocaproic acid 4-Aminobutanoic Acid g-Aminobutyric Acid Benzoic acid Benzenecarboxylic acid

Common Names

Physical properties 1. The boiling point and melting point are higher than corresponding ester due to the existence of H-bond between the molecules of acid. Lower members of aliphatic acids are liquid with pungent smell. 2. Lower members of aliphatic acids are soluble in water due to the formation of extensive H-bond with water molecules.

Physical properties 3. Molecular mass of acids is found to be doubled when dissolved in benzene due to the formation of dimer via H-bond formation.

Oxidation Methods Primary alcohols and aldehydes can be oxidized to the corresponding carboxylic acid by a variety of oxidizing agents. Most commonly, the oxidation is carried out in potassium permanganate, although heating with an acidic solution of potassium dichromate or with nitric acid will also work.

Oxidation of Primary Alcohols Example

FROM ALKYL SUBSTITUTED AROMATIC OMPOUNDS. Oxidation is accomplished using either potsssium permanganate or potassium dichromate. The product is always a substituted benzoic acid, irrespective of the length of the alkyl side-chain. The carbon atoms that are cleaved from the side-chain are converted to CO2. Can also use K2Cr2O7 + H2SO4 + heat

Oxidation of Side Chains Example

This reaction does not work with non-aromatic ring compounds. For example, an alkyl-substituted cyclohexane is unreactive in this procedure.

Preparation of Carboxylic Acids Oxidative cleavage of alkynes

Carbonation of Grignard Reagents Carbon dioxide has an electron-deficient carbon atom. It behaves as if it were two carbonyl groups glued together by their carbon atoms The carbon is thus a good site for nucleophilic attack.

Carbonation of Grignard Reagents Mechanism The carboxylate ion is protonated during the next (hydrolysis) step.

Example The carbon dioxide used in the these example was bubbled through the ether solution of the Grignard reagent as a gas (from a cylinder).

Example

Notice that, in the carbonation process, the carbon chain is extended by one carbon atom (e.g., if the alkyl halide has six carbons, the product will have seven carbons). The carbonation method also works with organolithium reagents.

Hydrolysis of Nitriles Another important method for the preparation of carboxylic acids is the hydrolysis of nitriles. Nitriles can be prepared by the nucleophilic substitution (SN2) reaction of cyanide ion reacting with an alkyl halide. Formation of Nitriles

The R group in this reaction must be either a primary or a secondary alkyl group. Tertiary alkyl halides and aryl halides do not react with cyanide ion (they can’t go SN2!). This is a limitation for this reaction that does not apply in the carbonation of a Grignard reagent. Once the nitrile has been prepared, it can be hydrolyzed to the carboxylic acid under either acidic or basic conditions.

Hydrolysis of Nitriles

Notice again that the carbon chain length has been extended by one carbon atom. Also recall that cyanide ion adds to aldehydes and ketones to form cyanohydrins (a-hydroxynitriles). These can also be hydrolyzed to carboxylic acids.

Example

The most important reactions of the carboxylic acids involve the conversion of the acids to the various derivatives (acid chlorides, esters, amides, etc.). Since these reactions all follow the same mechanistic pathway,.

Carboxylate Ion Formation Carboxylic acids react with aqueous base to yield the corresponding carboxylate salt. The carboxylate salts are much more soluble in water than are the corresponding unionized carboxylic acids. This property is used in solubility classification tests.

Chemical Properties Acid character Carboxylic acid is more acidic than alcohol and phenol due to the comparatively more stable carboxylate anion than alkoxide and phenoxide ion. The equilibrium position thus lie closer to the right hand side.

Chemical Properties Acid character Chlorine replacing hydrogen in alkyl group of the acid causes the acid to be more acidic since the chlorine has an negative inductive effect. This causes the negative charge in the carboxylate anion to be spread through the ion more effectively, i.e. more stable.

Chemical Properties Esterification Forward reaction is an acid-catalyzed esterification while the backward reaction is acid-catalyzed hydrolysis of ester.

Chemical Properties Esterification (cont’d) Saponification: In alkaline medium (hydrolysis of ester). (Not a equilibrium reaction)

Chemical Properties Reduction LiAlH4 is a very strong reduction agent (especially in organic compound). N.B. NaBH4 cannot reduce carboxylic acid.

Chemical Properties Replacement of –OH by -X 3 3

Chemical Properties Formation of amide

Chemical Properties Decarboxylation Chlorination

Chemical Properties – Special reaction for methanoic acid 1. Oxidation

Chemical Properties – Special reaction for methanoic acid 2. Dehydration 3.Decomposition by heating

Acid Derivatives The group bonded to the acyl carbon determines the class of compound: -OH, carboxylic acid -Cl, acid chloride -OR’, ester -NH2, amide These interconvert via nucleophilic acyl substitution. =>

Carboxylic acid derivatives If the -OH group is replaced carboxylic acid derivatives are formed.

Acid Derivatives All can be converted to the carboxylic acid by acidic or basic hydrolysis. Esters and amides common in nature. =>

2-methylpropyl ethanoate Naming Esters Esters are named as alkyl carboxylates. Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. isobutyl acetate 2-methylpropyl ethanoate benzyl formate benzyl methanoate =>

Cyclic Esters Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone. To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone. 4-hydroxy-2-methylpentanoic acid lactone -methyl--valerolactone =>

Amides Product of the reaction of a carboxylic acid and ammonia or an amine. Not basic because the lone pair on nitrogen is delocalized by resonance. Bond angles around N are close to 120. =>

Classes of Amides 1 amide has one C-N bond (two N-H). 2 amide or N-substituted amide has two C-N bonds (one N-H). 3 amide or N,N-disubstituted amide has three C-N bonds (no N-H). =>

Naming Amides For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide. For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position. N-ethyl-N,2-dimethylpropanamide N-ethyl-N-methylisobutyramide =>

Cyclic Amides Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam. To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam.

Acid Halides More reactive than acids; the halogen withdraws e- density from carbonyl. Named by replacing -ic acid with -yl halide. 3-bromobutanoyl bromide -bromobutyryl bromide => benzoyl chloride