Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Organic Chemistry, 5th Edition L. G. Wade, Jr. Chapter 21 Carboxylic Acid Derivatives Jo Blackburn Richland College, Dallas, TX Dallas County Community College District 2003, Prentice Hall Acid Derivatives • All can be converted to the carboxylic acid by acidic or basic hydrolysis. • Esters and amides common in nature. O R C X RCOX O O R C O C R' (RCO)2O O R C O R RCOOR O R C NH2 R C N RCONH2 RCN => Chapter 21 2 Naming Esters • Esters are named as alkyl carboxylates. • Alkyl from the alcohol, carboxylate from the carboxylic acid precursor. CH3 O O CH3CHCH2OCCH3 isobutyl acetate 2-methylpropyl ethanoate HCOCH2 benzyl formate benzyl methanoate => Chapter 21 3 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. O H3C O 4-hydroxy-2-methylpentanoic acid lactone -methyl--valerolactone CH3 => Chapter 21 4 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. O C H O N H H C + H N H H Bond angles around N are close to 120. Chapter 21 5 => 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). => Chapter 21 6 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 Nto indicate their position. O CH3 CH3CHC N N-ethyl-N,2-dimethylpropanamide CH2CH3 N-ethyl-N-methylisobutyramide CH3 Chapter 21 7 => 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. O N H CH3 4-aminopentanoic acid lactam -valerolactam => Chapter 21 8 Nitriles • -CN can be hydrolyzed to carboxylic acid, so nitriles are acid derivatives. • Nitrogen is sp hybridized, lone pair tightly held, so not very basic. (pKb about 24). => Chapter 21 9 Naming Nitriles • For IUPAC names, add -nitrile to the alkane name. • Common names come from the carboxylic acid. Replace -ic acid with -onitrile. Br C N CH3CHCH2CH2CH2CN 5-bromohexanenitrile -bromocapronitrile Cyclohexanecarbonitrile => Chapter 21 10 Acid Halides • More reactive than acids; the halogen withdraws e- density from carbonyl. • Named by replacing -ic acid with -yl halide. O C Br Cl O CH3CHCH2C Br 3-bromobutanoyl bromide -bromobutyryl bromide => benzoyl chloride Chapter 21 11 Acid Anhydrides • Two molecules of acid combine with the loss of water to form the anhydride. • Anhydrides are more reactive than acids, but less reactive than acid chlorides. • A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions. O R C O H O O H O C R O R C O C R => Chapter 21 12 Naming Anhydrides • The word acid is replaced with anhydride. • For a mixed anhydride, name both acids. • Diacids may form anhydrides if a 5- or 6membered ring is the product. O O O C O C CH3 O ethanoic anhydride acetic anhydride O CH3 1,2-benzenedicarboxylic anhydride phthalic anhydride => Chapter 21 13 Multifunctional Compounds • The functional group with the highest priority determines the parent name. • Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne. O C OCH2CH3 ethyl o-cyanobenzoate => CN Chapter 21 14 Boiling Points Even 3 amides have strong attractions. Chapter 21 => 15 Melting Points • Amides have very high melting points. • Melting points increase with increasing number of N-H bonds. O H C N CH3 CH3 m.p. -61C O CH3 C N O H CH3 m.p. 28C CH3CH2 C N H H m.p. 79C => Chapter 21 16 Solubility • Acid chlorides and anhydrides are too reactive to be used with water or alcohol. • Esters, 3 amides, and nitriles are good polar aprotic solvents. • Solvents commonly used in organic reactions: Ethyl acetate Dimethylformamide (DMF) Acetonitrile Chapter 21 =>17 IR Spectroscopy => => Chapter 21 18 1H NMR Spectroscopy => Chapter 21 19 13C NMR Spectroscopy => Chapter 21 20 Interconversion of Acid Derivatives • Nucleophile adds to the carbonyl to form a tetrahedral intermediate. • Leaving group leaves and C=O regenerates. _ O _ Nuc R C O Y O R C Y Nuc R C Nuc _ + Y => Chapter 21 21 Reactivity Reactivity decreases as leaving group becomes more basic. => Chapter 21 22 Interconversion of Derivatives More reactive derivatives can be converted to less reactive derivatives. => Chapter 21 23 Acid Chloride to Anhydride • Acid or carboxylate ion attacks the C=O. • Tetrahedral intermediate forms. • Chloride ion leaves, C=O is restored, H+ is abstracted. _ => O O O R' C O H R C O - H+ Cl R H C +O Cl R C O O C R' + HCl C R' O Chapter 21 24 Acid Chloride to Ester • Alcohol attacks the C=O. • Tetrahedral intermediate forms. • Chloride ion leaves, C=O is restored, H+ is abstracted. => _ O R' O H R C O Cl R C Cl +O H R' Chapter 21 O - H+ R C O R' + HCl 25 Acid Chloride to Amide • Ammonia yields a 1 amide • A 1 amine yields a 2 amide • A 2 amine yields a 3 amide _ O R'2 N H R C Cl R'2 O O R C Cl +N H R'2 C R N R'2 + + N H => Chapter 21 - R'2NH2 Cl 26 Anhydride to Ester • Alcohol attacks one C=O of anhydride. • Tetrahedral intermediate forms. • Carboxylate ion leaves, C=O is restored, H+ is abstracted. => R' O H R O O C C O _ O R O R C O C R +O H R' Chapter 21 O _ O C R O + R C 27 OR' Anhydride to Amide • Ammonia yields a 1 amide • A 1 amine yields a 2 amide • A 2 amine yields a 3 amide O R'2 N H R C _ O O C O R O R C O C R +N H R'2 O _ O C R O + R C NR'2 => Chapter 21 28 Ester to Amide • Nucleophile must be NH3 or 1 amine. • Prolonged heating required. _ O R' NH2 R C O OCH3 R C OCH3 +N H R' H O _ OCH3 + R C NH R' Surprise! => Chapter 21 29 Leaving Groups A strong base is not usually a leaving group unless it’s in an exothermic step. => Chapter 21 30 Transesterification • One alkoxy group can be replaced by another with acid or base catalyst. • Use large excess of preferred alcohol. O O C OCH CH 2 3 + + CH3OH - H or OCH3 C OCH 3 + CH3CH2OH => Chapter 21 31 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. O O CH3 CH3 C Cl + HOH C OH + HCl => Chapter 21 32 Acid Hydrolysis of Esters • Reverse of Fischer esterification. • Reaches equilibrium. • Use a large excess of water. O CH3 C OCH3 + HOH O + H CH3 C OH + CH3OH => Chapter 21 33 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 34 Hydrolysis of Amides Prolonged heating in 6 M HCl or 40% aqueous NaOH is required. O CH3 - C NHCH3 + OH O CH3 C NHCH3 + HCl H2O H2O O CH3 C O - + CH3NH2 O CH3 + - C OH + CH3NH3 Cl => Chapter 21 35 Hydrolysis of Nitriles • Under mild conditions, nitriles hydrolyze to an amide. • Heating with aqueous acid or base will hydrolyze a nitrile to an acid. C N + H2O - OH O O C NH 2 C O- - OH heat + NH3 => Chapter 21 36 Reduction to Alcohols Lithium aluminum hydride reduces acids, acid chlorides, and esters to primary alcohols. O C OCH CH 2 3 CH2OH 1) LiAlH4 2) H2O + CH3CH2OH => Chapter 21 37 Reduction to Aldehydes Acid chlorides will react with a weaker reducing agent to yield an aldehyde. CH3 O CH3CHCH2C Cl LiAl(t-BuO)3H CH3 O CH3CHCH2C H => Chapter 21 38 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. O CH3 C NHCH3 1) LiAlH4 2) H2O CH3 CH2 NHCH3 => Chapter 21 39 Organometallic Reagents Grignard reagents and organolithium reagents add twice to acid chlorides and esters to give alcohols after protonation. OH O C OCH CH 2 3 2 CH3MgBr ether H3O + C CH 3 CH3 => Chapter 21 40 Grignard Reagents and Nitriles A Grignard reagent or organolithium reagent attacks the cyano group to yield an imine which is hydrolyzed to a ketone. H3C C N CH3MgBr ether C N H3C MgBr H3O + C O => Chapter 21 41 Acid Chloride Synthesis • Use thionyl chloride, SOCl2, or oxalyl chloride, (COCl)2. • Other products are gases. O O C OH C Cl SOCl2 + SO2 + HCl => Chapter 21 42 Acid Chloride Reactions (1) O H2O R C OH + HCl acid O O R'OH + HCl ester R C NHR' + HCl amide R C OR' O R C Cl R'NH2 O R'COOH O R C O C R' + HCl acid anhydride Chapter 21 => 43 Acid Chloride Reactions (2) OH (1) 2 R'MgX (2) H2O R'2CuLi O R C R C R' 3° alcohol R' O R C ketone R' Cl (1) LiAlH4 (2) H2O Li(t-BuO)3AlH R CH2OH 1° alcohol O aldehyde R C H O Z AlCl3 C R Z acylbenzene => Chapter 21 44 Industrial Synthesis of Acetic Anhydride • Four billion pounds/year produced. • Use high heat (750°C) and triethyl phosphate catalyst to produce ketene. O CH3 C OH H H heat (EtO)3P O H C C O H O O C C O + CH3 C OH O CH3 C O C CH3 => Chapter 21 45 Lab Synthesis of Anhydrides • React acid chloride with carboxylic acid or carboxylate ion. O C Cl O O O C O C CH 3 _ + CH3 C O • Heat dicarboxylic acids to form cyclic O O anhydrides. C OH O C OH O Chapter 21 O => 46 Anhydride Reactions O H2O R C R O O C O C + RCOOH acid OR' + RCOOH ester NHR' + RCOOH amide O + R'OH, H OH R C O R R'NH2 R C O Z AlCl3 C R Z acylbenzene => Chapter 21 47 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. O O CH3 C O C H O + R NH2 O H C NHR + CH3 C OH • Use cyclic anhydrides to produce a difunctional molecule. O O C OCH CH 2 3 O O CH3CH2OH Chapter 21 C OH O => 48 Synthesis of Esters O O + R C OH + R'OH H R C OR' + HOH acid O O R C Cl R C OR' + HCl + R'OH acid chloride O O R C O C R + R'OH O + H R C OR' + RCOOH acid anhydride O R C OH + CH2N2 O R C OCH3 + N2 methyl ester Chapter 21 => 49 Reactions of Esters O H2O R C OH + R'OH acid R'OH ester O R''OH, + - H or OR'' O R C OR' R C OR'' + O R''NH2 (1) LiAlH4 (2) H2O (1) 2 R''MgX (2) H2O R C NHR'' + R CH2OH R'OH amide 1° alcohol OH R C R'' 3° alcohol R'' Chapter 21 => 50 Lactones • Formation favored for five- and sixmembered rings. OH H+ O + H2O COOH O • For larger rings, remove water to shift equilibrium toward products OH + O H COOH + H2O O => Chapter 21 51 Synthesis of Amides O O heat R C OH + R'NH2 R C NHR' + HOH acid O O R C NR'2 + R'2NH2+Cl- R C Cl + 2 R'2NH acid chloride O O O R C NR'2 + RCOOH R C O C R + R'2NH acid anhydride O O R C OR'' + R'NH2 R C NHR' + R''OH ester + R C N + H2O - H or OH nitrile O R C NH2 => Chapter 21 52 Reactions of Amides O H2O H+ or -OH O R C NHR' (1) LiAlH4 (2) H2O Br-, OHPOCl3 (or P2O5) R C OH + R'NH2 acid and amine R CH2NHR' amine R NH2 + CO2 R C N 1° amine nitrile => Chapter 21 53 Lactam Formation • Five- and six-membered rings can be formed by heating - and -amino acids. NH2 NH heat + H2O COOH O • Smaller or larger rings do not form readily. => Chapter 21 54 -Lactams • Highly reactive, 4-membered ring. • Found in antibiotics isolated from fungi. Amide ester !! => Chapter 21 55 Synthesis of Nitriles O R C NH2 POCl3 R C N 1° amide R X NaCN + R C N + Na X alkyl halide Ar + N N diazonium salt O R C R' aldehyde or ketone CuCN Ar CN + N2 HO CN HCN R C R' KCN cyanohydrin Chapter 21 => 56 Reactions of Nitriles O O H2O + H or OH R C N (1) LiAlH4 (2) H2O R'MgX R C NH2 amide R CH2NH2 N MgX R C R' H2O + H or OH R C OH acid 1° amine + H3O O R C R' ketone => Chapter 21 57 Thioesters More reactive than esters because: -S-R is a better leaving group than -O-R Resonance overlap is not as effective. => Chapter 21 58 Carbonic Acid Esters • CO2 in water contains some H2CO3. • Diesters are stable. • Synthesized from phosgene. O Cl C Cl O + 2 CH3CH2OH CH3CH2OCOCH2CH3 diethyl carbonate => Chapter 21 59 Urea and Urethanes • Urea is the diamide of carbonic acid. • Urethanes are esters of a monoamide of carbonic acid. O O Cl C Cl + N C O H2O H2N C NH2 urea 2 NH3 O O NH C OH NH C OR a carbamic acid Chapter 21 ROH => a urethane 60 Polymers • Polycarbonates are long-chain esters of carbonic acid. • Polyurethanes are formed when a diol reacts with a diisocyanate. O O C N N C O O CH2CH2 O C HN O NH C HOCH2CH2OH CH3 CH3 n => Chapter 21 61 End of Chapter 21 Chapter 21 62