Chapter 21 Carboxylic Acid Derivatives (continued) Organic Chemistry, 6th Edition L. G. Wade, Jr. Chapter 21 Carboxylic Acid Derivatives (continued) Jo Blackburn Richland College, Dallas, TX Dallas County Community College District ã 2006, Prentice Hall

Hydrolysis of Acid Chlorides and Anhydrides Hydrolysis occurs quickly, even in moist air with no acid or base catalyst. Reagents must be protected from moisture. => Chapter 21

Acid Hydrolysis of Esters Reverse of Fischer esterification. Reaches equilibrium. Use a large excess of water. => Chapter 21

Saponification Base-catalyzed hydrolysis of ester. “Saponification” means “soap-making.” Soaps are made by heating NaOH with a fat (triester of glycerol) to produce the sodium salt of a fatty acid - a soap. One example of a soap is sodium stearate, Na+ -OOC(CH2)16CH3. => Chapter 21

Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required. => Chapter 21

Hydrolysis of Nitriles Under mild conditions, nitriles hydrolyze to an amide. Heating with aqueous acid or base will hydrolyze a nitrile to an acid. => Chapter 21

Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols. => Chapter 21

Reduction to Aldehydes Acid chlorides will react with a weaker reducing agent to yield an aldehyde. => Chapter 21

Reduction to Amines Lithium aluminum hydride reduces amides and nitriles to amines. Nitriles and 1 amides reduce to 1 amines. A 2 amide reduces to a 2 amine. A 3 amide reduces to a 3 amine. => Chapter 21

Organometallic Reagents Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation. => Chapter 21

Grignard Reagents and Nitriles A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone. => Chapter 21

Acid Chloride Synthesis Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2. Other products are gases. => Chapter 21

Acid Chloride Reactions (1) ester amide acid anhydride => Chapter 21

Acid Chloride Reactions (2) 3° alcohol ketone 1° alcohol aldehyde acylbenzene => Chapter 21 AlCl3

Industrial Synthesis of Acetic Anhydride Four billion pounds/year produced. Use high heat (750°C) and triethyl phosphate catalyst to produce ketene. => Chapter 21

Lab Synthesis of Anhydrides React acid chloride with carboxylic acid or carboxylate ion. Heat dicarboxylic acids to form cyclic anhydrides. => Chapter 21

Anhydride Reactions acid ester amide acylbenzene => AlCl3 Chapter 21

Anhydride vs. Acid Chloride Acetic anhydride is cheaper, gives a better yield than acetyl chloride. Use acetic formic anhydride to produce formate esters and formamides. Use cyclic anhydrides to produce a difunctional molecule. => Chapter 21

Synthesis of Esters acid acid chloride acid anhydride => methyl ester => Chapter 21

Reactions of Esters acid ester amide 1° alcohol 3° alcohol => Chapter 21

Lactones Formation favored for five- and six-membered rings. For larger rings, remove water to shift equilibrium toward products => Chapter 21

Polyesters Dacron® thread Mylar® tape Glyptal resin PET bottles => Chapter 21

Synthesis of Amides acid acid chloride acid anhydride ester nitrile => Chapter 21

Reactions of Amides acid and amine amine 1° amine nitrile => Chapter 21

Lactam Formation Five- and six-membered rings can be formed by heating - and -amino acids. Smaller or larger rings do not form readily. => Chapter 21

-Lactams Highly reactive, 4-membered ring. Found in antibiotics isolated from fungi. Amide  ester !! => Chapter 21

Polyamides Nylon 6.6 => Chapter 21

Synthesis of Nitriles 1° amide alkyl halide diazonium salt aldehyde or ketone cyanohydrin => Chapter 21

Reactions of Nitriles amide acid 1° amine ketone => Chapter 21

Thioesters More reactive than esters because: -S-R is a better leaving group than -O-R Resonance overlap is not as effective. => Chapter 21

Carbonic Acid Esters CO2 in water contains some H2CO3. Diesters are stable. Synthesized from phosgene. => phosgene Chapter 21

Urea and Urethanes Urea is the diamide of carbonic acid. Urethanes are esters of a monoamide of carbonic acid. => Chapter 21

Long-chain esters of carbonic acid Polycarbonates Long-chain esters of carbonic acid => Chapter 21

A diol reacts with a diisocyanate. Polyurethanes A diol reacts with a diisocyanate. => Chapter 21

End of Chapter 21 Chapter 21