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1、19.1419.14Mechanism of Acid-Catalyzed EsterificationMechanism of Acid-Catalyzed EsterificationAcid-catalyzed EsterificationAcid-catalyzed Esterification+ +CHCH3 3OOH HCOHCOHOOH H+ + +H H2 2OOC COOCHCH3 3OOImportant fact: the Important fact: the oxygenoxygen of the alcohol is of the alcohol isincorpo
2、rated into the ester as shown.incorporated into the ester as shown.(also called Fischer esterification)(also called Fischer esterification)The mechanism involves two stages: The mechanism involves two stages: 1)1) formation of tetrahedral intermediateformation of tetrahedral intermediate(3 steps)(3
3、steps)2)2) dissociation of tetrahedral intermediate dissociation of tetrahedral intermediate (3 steps)(3 steps)Mechanism of Fischer EsterificationMechanism of Fischer EsterificationThe mechanism involves two stages: The mechanism involves two stages: 1)1) formation of tetrahedral intermediateformati
4、on of tetrahedral intermediate(3 steps)(3 steps)2)2) dissociation of tetrahedral intermediate dissociation of tetrahedral intermediate (3 steps)(3 steps)Mechanism of Fischer EsterificationMechanism of Fischer EsterificationC COHOHOHOHOOCHCH3 3tetrahedral intermediate in esterification tetrahedral in
5、termediate in esterification of benzoic acid with methanolof benzoic acid with methanolFirst stage: First stage: formation of tetrahedral intermediateformation of tetrahedral intermediateC COHOHOHOHOOCHCH3 3+ +CHCH3 3OOH HCOHCOHOOH H+ +methanol adds to the methanol adds to the carbonyl group of the
6、carbonyl group of the carboxylic acidcarboxylic acidthe tetrahedral the tetrahedral intermediate is intermediate is analogous to a analogous to a hemiacetalhemiacetalSecond stage: Second stage: conversion of tetrahedralconversion of tetrahedralintermediate to esterintermediate to esterC COHOHOHOHOOC
7、HCH3 3+ +H H2 2OOH H+ +this stage corresponds this stage corresponds to an acid-catalyzed to an acid-catalyzed dehydrationdehydrationC COOCHCH3 3OOMechanism of formationMechanism of formationofoftetrahedral intermediatetetrahedral intermediateStep 1Step 1C COOOOH H OO + +H HCHCH3 3H HStep 1Step 1C C
8、OOOOH H OO + +H HCHCH3 3H H C COOOOH H + +H H OO CHCH3 3H HStep 1Step 1 C COOOOH H + +H Hcarbonyl oxygen is carbonyl oxygen is protonated because protonated because cation produced is cation produced is stabilized by electron stabilized by electron delocalization delocalization (resonance)(resonance
9、)C COOOOH H + +H H Step 2Step 2 C COOOOH H + +H H OO CHCH3 3H HStep 2Step 2 C COOOOH H + +H H OO CHCH3 3H HC COHOHOHOH OO + +CHCH3 3H HStep 3Step 3 OO CHCH3 3H H C COHOHOHOH OO CHCH3 3H H+ +Step 3Step 3 OO CHCH3 3H H C COHOHOHOH OO CHCH3 3H H+ +OO CHCH3 3H HH H+ + C COHOHOHOH OO CHCH3 3 Tetrahedral
10、intermediateTetrahedral intermediatetotoester stageester stageStep 4Step 4 C COHOHOO OOCHCH3 3 H HStep 4Step 4OO CHCH3 3H HH H+ + C COHOHOO OOCHCH3 3 H HStep 4Step 4OO CHCH3 3H HH H+ + C COHOHOO OOCHCH3 3 H H C COHOHOO OOCHCH3 3 H HH H+ + OO CHCH3 3H HStep 5Step 5 C COHOHOO OOCHCH3 3 H HH H+ +Step 5
11、Step 5 C COHOHOO OOCHCH3 3 H HH H+ +OO H HH H + +C COHOH OOCHCH3 3 + +Step 5Step 5C COHOH OOCHCH3 3 + +C COHOH OOCHCH3 3 + +Step 6Step 6C COO OOCHCH3 3 + +H HOO H HCHCH3 3 + +OOH HCHCH3 3 H HC COO OOCHCH3 3 Activation of carbonyl group by protonation of Activation of carbonyl group by protonation of
12、 carbonyl oxygencarbonyl oxygenNucleophilic addition of alcohol to carbonyl groupNucleophilic addition of alcohol to carbonyl groupforms tetrahedral intermediateforms tetrahedral intermediateElimination of water from tetrahedral intermediate Elimination of water from tetrahedral intermediate restore
13、s carbonyl grouprestores carbonyl groupKey Features of MechanismKey Features of Mechanism19.1519.15Intramolecular Ester Formation:Intramolecular Ester Formation:LactonesLactonesLactones are cyclic estersLactones are cyclic estersFormed by intramolecular esterification in aFormed by intramolecular es
14、terification in acompound that contains a hydroxyl group andcompound that contains a hydroxyl group anda carboxylic acid functiona carboxylic acid functionLactonesLactones ExamplesExamplesH HOOCHCH2 2CHCH2 2CHCH2 2COHCOHOOOOOO+ +H H2 2OO4-hydroxybutanoic acid4-hydroxybutanoic acid4-butanolide4-butan
15、olideIUPAC nomenclature: replace the IUPAC nomenclature: replace the -oic acid -oic acid ending of the carboxylic acid by ending of the carboxylic acid by -olide-olideidentify the oxygenated carbon by numberidentify the oxygenated carbon by number ExamplesExamplesH HOOCHCH2 2CHCH2 2CHCH2 2COHCOHOOH
16、HOOCHCH2 2CHCH2 2CHCH2 2CHCH2 2COHCOHOOOOOOOOOO+ + +H H2 2OOH H2 2OO4-hydroxybutanoic acid4-hydroxybutanoic acid5-hydroxypentanoic acid5-hydroxypentanoic acid4-butanolide4-butanolide5-pentanolide5-pentanolide Common namesCommon namesOOOOOOOOg g-butyrolactone-butyrolactoned d-valerolactone-valerolact
17、onea aa ab bb bg gg gd dRing size is designated by Greek letter Ring size is designated by Greek letter corresponding to oxygenated carboncorresponding to oxygenated carbonA A g g lactone has a five-membered ring lactone has a five-membered ringA A d d lactone has a six-membered ring lactone has a s
18、ix-membered ringReactions designed to give hydroxy acids often Reactions designed to give hydroxy acids often yield the corresponding lactone, especially if theyield the corresponding lactone, especially if theresulting ring is 5- or 6-membered.resulting ring is 5- or 6-membered.LactonesLactonesExam
19、pleExample5-hexanolide (78%)5-hexanolide (78%)OOH H3 3C COOCHCH3 3CCHCCH2 2CHCH2 2CHCH2 2COHCOHOOOO1. NaBH1. NaBH4 42. H2. H2 2O, HO, H+ +ExampleExample5-hexanolide (78%)5-hexanolide (78%)via:via:OOH H3 3C COOCHCH3 3CCHCCH2 2CHCH2 2CHCH2 2COHCOHOOOO1. NaBH1. NaBH4 42. H2. H2 2O, HO, H+ +CHCH3 3CHCHCHCH2 2CHCH2 2CHCH2 2COHCOHOOOOH H
