Unit 11 - Carboxylic Acids and Their Derivatives

Ozonolysis forming carboxylic acids

• Alkyne → two carboxylic acids

• 1. O3 2. H2O

Chromic acid oxidation of a primary alcohol

• Primary alcohol → carboxylic acid

• Na2Cr2O7, H2SO4, H2O

Oxidation of alkyl benzenes

• Alkyl benzene → carboxylic acid

• Strong oxidizing agent like chromic acid or KMnO4

KMnO4 oxidation of an alkene

• Alkene → carboxylic acid

• Syn dihydroxylation followed by bond cleavage and formation of two carboxylic acid groups

Hydrolysis of nitriles

• Nitrile → 1 amide → carboxylic acid

• H3O+, heat

• Allows conversion of alkyl halides to carboxylic acids by using SN2 to substitute CN- and form a nitrile

Carboxylation of Grignard reagents using CO2

• CO2 → carboxylic acid

• RMgX, acid workup

• Allows conversion of alkyl halides to carboxylic acids by using Mg to form a Grignard + treating with CO2

• Mechanism: R- attacks carbonyl C, acid workup

Reduction of carboxylic acids using LAH

• carboxylic acid → 1 alcohol

• LAH, H3O+

Deriving anhydrides from carboxylic acids

Add a carboxylate ion

Deriving amides from carboxylic acids

Add an amine (NH3 amine → 1 amine, 1 amine → 2 amide, 2 amine → 3 amide)

Deriving nitriles from amides

Dehydrate a 1 amide

Deriving an ester from carboxylic acids

Add 1. NaOH to obtain carboxylate 2. methyl or primary RX via SN2

Deriving acid chloride from carboxylic acids

Add SOCl2

Nucleophilic acyl substitution

• Carboxylic acid derivative → different carboxylic acid derivative, nucleophile replaced the LG

• Nucleophile attacks carbonyl C, tetrahedral intermediate forms and collapses, carbonyl group reforms and leaving group leaves

• Basic format for all conversions of derivatives

Nucleophilic acyl substitution in basic conditions

OH- attacks the carbonyl C first, tetrahedral intermediate collapses, carbonyl reforms

Nucleophilic acyl substitution in acidic conditions

H3O+ protonates the carbonyl O first, nucleophilic water attacks the carbonyl C, water is deprotonated by more water, LG is protonated, LG loss and carbonyl reform, carbonyl is deprotonated

Anhydride synthesis from acid chloride

• Acid chloride → anhydride

• Carboxylate ion

• Nucleophilic acyl substitution in basic conditions

Ester synthesis from acid chloride

• Acid chloride → ester

• ROH, pyridine

• Nucleophilic acyl substitution in basic conditions, pyridine deprotonates OH to form the ester

Amide synthesis from acid chloride

• Acid chloride → amide

• 2 equivalents of amine

• Nucleophilic acyl substitution in basic conditions

• Second amine equivalent deprotonates NH2, forming the amide

Primary alcohol synthesis from acid chloride

• Acid chloride → 1 alcohol

• xs LAH, H2O

• Nucleophilic acyl substitution in basic conditions, for some reason NH4- first converts it to an aldehyde, then LAH reduces the aldehyde

Tertiary alcohol synthesis from acid chloride

• Acid chloride → 3 alcohol

• 1. xs RMgX 2. H2O

• Nucleophilic acyl substitution in basic conditions, forms a ketone intermediate

Gilman reagent (R2CuLi)

• Acid chloride → ketone instead of progressing to 3 alcohol

Fischer esterification

• Carboxylic acid + alcohol → ester

• H3O+, ROH

• Nucleophilic acyl substitution in acidic conditions

Saponification

• Ester → carboxylic acid + alcohol

• 1. NaOH 2. H3O+

• Nucleophilic acyl substitution in basic conditions, acid workup converts carboxylate to carboxylic acid

Ester hydrolysis in acidic conditions

• Ester → carboxylic acid + alcohol

• H3O+

• Nucleophilic acyl substitution in acidic conditions

• Exact reverse of Fischer esterification

Ester reduction with LAH

• Ester → two 1 alcohols

• 1. xs LAH 2. H2O

• Nucleophilic acyl substitution in basic conditions, involves an aldehyde intermediate (so LAH reduces twice)

• One alcohol is from the ester, one is from the leaving group OR-

• Analogous to acid chloride → 1 alcohol

Ester reduction with Grignard

• Ester → 3 alcohol

• 1. xs RMgX 2. H2O

• Nucleophilic acyl substitution in basic conditions, involves a ketone intermediate (so R- reduces twice)

• Analogous to acid chloride → 3 alcohol

Amide reduction with LAH

• Amide → corresponding amine

• 1. xs LAH 2. H2O