Carboxylic acids and their derivatives

Structure

Structure of derivatives acyl halide anhydride acid halide ester amide

The acyl group

Nomenclature HCO2H formic acid (from Latin formica, ant) CH3CO2H acetic acid (from Latin acetum, vinegar) CH3CH2CO2H propionic acid (from Greek protos, first and piôn, fat) CH3(CH2)2CO2H butyric acid (from Latin butyrum, butter) CH3(CH2)3CO2H valeric acid (valerian root) CH3(CH2)4CO2H caproic acid (from Latin caper, goat) CH3(CH2)6CO2H caprylic acid CH3(CH2)8CO2H capric acid

Nomenclature -aminobutyric acid

Nomenclature -hydroxypropionic acid or lactic acid isocaproic acid

Aromatic acids p-bromobenzoic acid m-toluic acid

Aldehydes - non-systematic names form(ic acid)aldehyde b-methylvaleraldehyde

IUPAC CH3CH2CO2H propanoic acid (CH3)2CHCH2CH2CO2H 4-methylpentanoic acid 2-hydroxy-5-methyl-3-hexenoic acid (CH3)2CHCH=CHCH(OH)CO2H C-1

Cyclic acids Saturated cyclic acids are named as cycloalkanecarboxylic acids: cis-2-methylcyclohexanecarboxylic acid

Salts of carboxylic acids sodium benzoate (CH3CO2)2Ca calcium acetate or calcium ethanoate

Nomenclature of derivatives

Nomenclature of acyl halides Change -ic acid to -yl halide

Nomenclature of anhydrides change acid to anhydride

Nomenclature of amides change -ic or -oic acid to -amide

Nomenclature of esters change -ic acid to name of alcohol group or phenol + -ate

Order of precedence of functional groups

Physical properties Intermolecular hydrogen bonding is very important. In the solid and liquid states, carboxylic acids exist as dimers. Mp and bp values are far higher than the corresponding alcohols.

Physical properties of acid derivatives Polar compounds: the acyl halides, anhydrides, and esters have boiling points which are very similar to those of aldehydes and ketones of equivalent molecular weight. However, the amides.......

Dissociation of carboxylic acids ~ 10-5

Relative acidities Relative basicities

Acidity of carboxylic acids

Structure of carboxylate ions

Substituent effects CH3CO2H ClCH2CO2H Cl2CHCO2H Cl3CCO2H Ka 1.76x10-5 136x10-5 5530x10-5 23200x10-5 HCO2H CH3CO2H CH3CH2CH2CO2H Ka 17.7x10-5 1.76x10-5 1.52x10-5

Salts of carboxylic acids crystalline, non-volatile, decompose on heating to 300 - 400C. sodium, potassium and ammonium salts are all water soluble and insoluble in non-polar solvents.

Salts of carboxylic acids water insoluble water soluble NB: Phenols do not react with bicarbonate.

Preparation of carboxylic acids

Oxidation of primary alcohols

Oxidation of arenes

Oxidation of arenes

The haloform reaction

Carboxylation of Grignard reagents

Carboxylation of Grignard reagents 2,2-dimethylpropanoic acid

Hydrolysis of nitriles + NH3

Preparation of nitriles - an SN2 reaction CH3CH2CH2CH2Br + CN-  CH3CH2CH2CH2CN primary halide (CH3)3CBr + CN-  (CH3)2C=CH2 + HCN

Nomenclature of nitriles CH3CH2CN - 3 carbon chain propane + nitrile = propanenitrile propionic acid - ic acid + onitrile = propiononitrile ethanenitrile acetonitrile CH3CN pentanenitrile valeronitrile CH3(CH2)3CN

The acyl group

Reactivity of aldehydes and ketones

Reactivity of carboxylic acid derivatives – nucleophilic addition - elimination G = -OH, -X, -OOCR, -NH2, or -OR Why?

Reactivity of carboxylic acid derivatives The ease of loss of the leaving group, G, depends on its basicity: G = HO-, X-, RCO2-, NH2- , or RO- G = H-, R- ?

Reactivity of carboxylic acid derivatives

Base hydrolysis

Acid hydrolysis

SN2 v acyl substitution

Nucleophilic displacement - reactivity

Haloform reaction

Haloform reaction

acid chlorides Use thionyl chloride (SOCl2), phosphorus trichloride (PCl3) or phosphorus pentachloride (PCl5).

acid chlorides

Reactions of acyl halides - conversion into acids + HCl benzoyl chloride benzoic acid

Reactions of acyl halides - conversion into amides + NH4Cl

Reactions of acyl halides - conversion into esters

Reactions of acyl halides - Friedel - Crafts’ acylation

Reactions of acyl halides with diorganocopper reagents A Gilman reagent

Reactions of acyl halides - the Rosemund reduction RCHO or ArCHO A special catalyst is used: palladium on barium sulfate which has been deactivated (poisoned) with an amine such as quinoline.

Lithium tri-tert-butoxyaluminium hydride

Anhydrides - preparation of acetic anhydride

Preparation of other anhydrides Nucleophilic substitution of an acyl halide with a carboxylate anion.

Hydrolysis of anhydrides acetic acid

Aminolysis of anhydrides + CH3CO2- NH4+ acetamide ammonium acetate

Alcoholysis of anhydrides + CH3CO2H methyl acetate

Acylation

Preparation of esters

Preparation of esters

Preparation of esters

Reactions - base hydrolysis rate = k[OH-][ester] How can we prove that OH- attacks the acyl carbon and not the alkyl carbon?

Reactions - base hydrolysis

Predicted result for alkyl - oxygen bond breaking

Predicted result for acyl - oxygen bond breaking So what happens when we perform the reaction? (+)-2-butanol is obtained - [] = +13.8o acyl - oxygen bond breaking occurs

Acyl - oxygen bond breaking - further proof using isotopic labels

However......?

Reactions - acid hydrolysis + H OH + R OR' R O R'

Reactions - acid hydrolysis

Aminolysis of esters

Transesterification

Transesterification - acid catalysed

Transesterification - basic conditions

Transesterification - a preparation of polyvinyl alcohol

Reactions of ester with Grignard reagents

Preparation of amides

Preparation of amides from acyl chlorides

Preparation of amides from acyl chlorides N-phenylbutanamide

Reactions - acid catalysed hydrolysis

Reactions - base hydrolysis

Hofmann degradation

Hofmann degradation

Reduction of acids 1o alcohol

Reduction of esters

Hell-Volhard-Zelinsky reaction

a-Halocarboxylic acids

a-Halocarboxylic acids dicarboxylic acid

Hell-Volhard-Zelinsky reaction enol

Spectroscopy IR: C=O stretching ~ 1710 cm-1 (dimer), ~1760 cm-1 (monomer) O-H stretching - broad range (3400 - 3600 cm-1) NMR: OH proton occurs in the region  = 9-13 ppm.

Problems Try problems 18.19 (a - g and m), 18.20, 18.21, 18.23, 18.24, 18.28, 18.29, 18.33, 18.35, 18.36, 18.41, 18.45 and 18.52.