wwu-chemistry carboxylic acid derivatives: nucleophilic acyl substitution chapter 19
TRANSCRIPT
WWU-ChemistryWWU-Chemistry
Carboxylic Acid Derivatives:Carboxylic Acid Derivatives:Nucleophilic Acyl SubstitutionNucleophilic Acyl Substitution
Chapter 19
WWU-ChemistryWWU-Chemistry
AssignmentAssignment• Skip the following sections:
19.1, 19.11, 19.15, 19.16, 19.18,
19.21 and 19.32
These PowerPoint slides have been revised for Fall 2007. Some additional sections
have been dropped or minimized!
WWU-ChemistryWWU-Chemistry
Problem AssignmentProblem Assignment
• In-Text:
1 a, c 4, 5a - d, 6 a - c 8 a, c
9 -11 15 - 19 21 - 23 26, 27 31 - 40
• End-of-Chapter:
4 6 - 9 15
WWU-ChemistryWWU-Chemistry
The addition/elimination The addition/elimination mechanismmechanism
WWU-ChemistryWWU-Chemistry
Nucleophilic Acyl SubstitutionNucleophilic Acyl Substitution1)
: :
R C Y
O
+ Nu:
slow
:..:
R C Y
O
Nu
2)
:..:
R C Y
O
Nu
: :
R C
O
Nu
+ Y:
_
_
Addition
Elimination
WWU-ChemistryWWU-Chemistry
Sect. 19.2, 19.3 and 19.4Sect. 19.2, 19.3 and 19.4Nomenclature for acid chlorides, Nomenclature for acid chlorides,
acid anhydrides and estersacid anhydrides and esters
Only ester nomenclature on test!
WWU-ChemistryWWU-Chemistry
CH3 C O CH2 CH3
O
Acid part of ester Alcohol part of ester
WWU-ChemistryWWU-Chemistry
CH3 C O CH2 CH3
O
Ethyl ethanoate (IUPAC)
Ethyl acetate (common)
WWU-ChemistryWWU-Chemistry
Methyl 2-methylpropanoate
CH3 CH C O CH3
CH3
O
WWU-ChemistryWWU-Chemistry
Ethyl pentanoate
CH3 CH2 CH2 CH2 C O CH2 CH3
O
WWU-ChemistryWWU-Chemistry
Methyl cyclohexanecarboxylate
H
C
OCH3
O
WWU-ChemistryWWU-Chemistry
Isopropyl benzoate or 2-methylethyl benzoate
C O
O
CH CH3
CH3
WWU-ChemistryWWU-Chemistry
Br
OEt
O
12
34
5
6
Ethyl 5-bromo-3,4-dimethylhexanoate
WWU-ChemistryWWU-Chemistry
Br
OEt
O
12
3
4
56
Ethyl 5-bromo-3,4-dimethyl-2,4-hexadienoate
WWU-ChemistryWWU-Chemistry
Sect. 19.5 and 19.6: Sect. 19.5 and 19.6: Nomenclature for amides and Nomenclature for amides and
nitrilesnitriles
Skip these sections! Not on test!
WWU-ChemistryWWU-Chemistry
Sect. 19.7: MechanismsSect. 19.7: MechanismsBase hydrolysis of an ester
R OCH3
O
RO
CH3
O
HO
addition elimination
R O
O
Ester
O-HNa+
Na+
O-CH3H
Na+
R O
OO-CH3
Na+
Hsodium saltof carboxylicacid
WWU-ChemistryWWU-Chemistry
Sect. 19.8/ 19.9: Preparation and Sect. 19.8/ 19.9: Preparation and reactions of acid chloridesreactions of acid chlorides
+ SOCl2R C OH
O
R C Cl
O
+
+
O S O
H Clthionyl chloride
Important!!! Acid chlorides are key intermediates for making esters, amides and anhydrides!!!!
WWU-ChemistryWWU-Chemistry
Preparation of an EsterPreparation of an Ester
CR
O
Cl OHR
CR
O
O H-ClR
acid chloride alcohol ester
WWU-ChemistryWWU-Chemistry
Preparation of an AmidePreparation of an Amide
CR
O
Cl NHR
H
primary amine
CR
O
Cl NHR
R
CR
O
NR
HH-Cl
CR
O
NR
R
H-Cl
secondaryamine
amide
amide
WWU-ChemistryWWU-Chemistry
Preparation of an AnhydridePreparation of an Anhydride
CR
O
Cl OH H-Cl
O
R
R
O
O
O
R
acid chloride carboxylic acid
anhydride
WWU-ChemistryWWU-Chemistry
Sect. 19.10: Reducing agentsSect. 19.10: Reducing agents
• Review of reductions on acid chlorides.
• A look at the reduction of all the derivatives of carboxylic acids.
• We talked about this in Chapter 16!
WWU-ChemistryWWU-Chemistry
Reactions of sodium borohydrideReactions of sodium borohydrideReactions of sodium borohydrideReactions of sodium borohydride
• Aldehydes yield primary alcohols
• Ketones yield secondary alcohols
• Esters give no reaction!
• Amides give no reaction!
WWU-ChemistryWWU-Chemistry
Reactions of lithium aluminum Reactions of lithium aluminum hydridehydride
Reactions of lithium aluminum Reactions of lithium aluminum hydridehydride
• Aldehydes give primary alcohols
• Ketones give secondary alcohols
• Esters give primary alcohols from the
carboxylic acid part of the ester (Sect 19.20)
• Amides give primary amines!! (Sect 19.24)
WWU-ChemistryWWU-Chemistry
Sect. 19.11: skipSect. 19.11: skip
WWU-ChemistryWWU-Chemistry
Sect. 19.12: carboxylic acid Sect. 19.12: carboxylic acid derivatives derivatives
Esters
Amides
Anhydrides
Nitriles
All of these functional groups will be hydrolyzed in acidic or basic water to give the parent carboxylic acid
WWU-ChemistryWWU-Chemistry
Sect. 19.13 and 9.14: EstersSect. 19.13 and 9.14: Esters
WWU-ChemistryWWU-Chemistry
Esters as Flavoring SubstancesEsters as Flavoring Substances
Isopentyl acetate Ethyl butyrate
banana pineapple
Isobutyl propionate Octyl acetaterum orange
Propyl acetate Methyl butyratepear apple
CH3 C O CH2 CH2 CH3
O
CH3 CH2 C O CH2 CH CH3
O
CH3
CH3 C O CH2 CH2 CH2
O
CH2 CH2 CH2 CH2 CH3
CH3 CH2 CH2 C O CH2 CH3
O
CH3 C O CH2 CH2 CH
O
CH3
CH3
CH3 CH2 CH2 C O CH3
O
WWU-ChemistryWWU-Chemistry
Fischer EsterificationFischer Esterification
+
+
O
CR OH
H+ O
CRR OH O R
OH H
ESTERIFICATION REACTIONS ARE REVERSIBLE. You needto push it to the right (ester) by removing water as it forms. This reaction is acid catalyzed
WWU-ChemistryWWU-Chemistry
Fischer esterification is an acid catalyzed reaction
RC
OH
OH+
RC
OH
OH
H-O-Et
R C O-H
O
OH Et
Haddition
R C O-H
O
OEt
H
carbon hybridizationis sp2 carbon hybridization
is sp3
R C O-H
O
OEt
H
- H+
H+
R C O-H
O
OEt
HH- H2O C
O-H
O-Et
RC
O
O-Et
R - H+
RC
OEt
O
H
elimination
resonance! sp2carbon
WWU-ChemistryWWU-Chemistry
Sect. 19.15 and 19.16 -- skipSect. 19.15 and 19.16 -- skip
WWU-ChemistryWWU-Chemistry
Sect. 19.17: Hydrolysis of EstersSect. 19.17: Hydrolysis of Esters
O
CR O R + OH_
+
O
CR O R + +H2OH
+
R O H
O
CR OH R O H
O
CR O
Mechanism of the acid catalyzed hydrolysis reaction is the reverse of the Fischer esterification reaction!
See slide for section 19.7 for mechanism of base hydrolysis
WWU-ChemistryWWU-Chemistry
Sect. 19.18: skipSect. 19.18: skip
WWU-ChemistryWWU-Chemistry
Sect. 19.19: Reaction of Esters Sect. 19.19: Reaction of Esters with Organometallic Reagentswith Organometallic Reagents
+ 2
O
CR O R
1) ether
2) H2O, acid
+ MgBr (OR) + MgBr(OH)R C R
OH
R
R MgBr
WWU-ChemistryWWU-Chemistry
Mechanism
R OCH3
O
MgBr-R
R OCH3
O
R
MgBr
addition elimination
R R
OBrMgO-CH3
Esterketone intermediate
R R
O
MgBr-R
addition
R RR
OMgBr
H3O+
R RR
OH
Tertiary alcohol
HO-CH3 from
ketone, notisolated!
This reaction requires one mole of ester and two moles of a Grignard reagent
WWU-ChemistryWWU-Chemistry
Sect. 19.20: Reduction of EstersSect. 19.20: Reduction of EstersLithium aluminum hydride gives the primary alcohol
OEt
O
LiAlH4
H hydride from
Addition
OEt
O
H
EliminationO
H
Aldehyde intermediate
O-Et
O
H
H
H
O
H H3O+
H
OH
H
also HO-Et from ester
WWU-ChemistryWWU-Chemistry
Diisobutylaluminum hydride (DibalH) gives the aldehyde
OEt
O
hydride from
Addition
OEt
O
H
EliminationO
H
O-Et
i-butylAl H
i-butyl
H
i-butylAl
i-butyl
WWU-ChemistryWWU-Chemistry
Sect. 19.21: skipSect. 19.21: skip
WWU-ChemistryWWU-Chemistry
Sect. 19.22 and 19.23: Sect. 19.22 and 19.23: Preparation and Reactions of Preparation and Reactions of
AmidesAmides
+ +R NH2O
HH
COH
O
RC
O
R NHRHeat
WWU-ChemistryWWU-Chemistry
Remember, also prepare amides Remember, also prepare amides from acid chloridesfrom acid chlorides
CR
O
Cl NHR
H
primary amine
CR
O
Cl NHR
R
CR
O
NR
HH-Cl
CR
O
NR
R
H-Cl
secondaryamine
WWU-ChemistryWWU-Chemistry
Amides, continuedAmides, continued
• Keep this section simple, skip the DCC stuff
WWU-ChemistryWWU-Chemistry
Sect. 19.24: Reduction of amidesSect. 19.24: Reduction of amidesamides give primary amines with lithium aluminum hydride.
NH2
O
LiAlH4
H hydride from
Addition
NH2
H3Al-O
H
Elimination NH2
H
NH2
H
O-AlH3
protonated imine intermediate
NH2
H
protonated imine intermediate
H
H
primary amine
amide
WWU-ChemistryWWU-Chemistry
Sect. 19.25 and 19.26: Reactions Sect. 19.25 and 19.26: Reactions of anhydridesof anhydrides
CR
O
ONH
R
H
primary amine
CR
O
NR
H
CR
O
HOC
R
O
amide carboxylic acid
CR
O
OH C
R
O
OC
R
O
HOC
R
O
carboxylic acid
OR
R
esteralcohol
WWU-ChemistryWWU-Chemistry
Preparation of aspirin and acetaminophen (Tylenol)
O
O
H
OH
salicylic acid
H3C
O
O
O
CH3
O
O
H
O
O CH3
H3C
O
OH
aspirin
N
HO
H
H
H3C
O
O
O
CH3
N
HO
H
O
CH3 H3C
O
OH
acetaminophen(Tylenol)
WWU-ChemistryWWU-Chemistry
Sect. 19.27 and 19.28:Sect. 19.27 and 19.28: preparation and reactions of nitrilespreparation and reactions of nitriles
Br Na+ C N
Carbon is a better nucleophilethan nitrogen
C N
NaBr
SN2Nitrile
C N
4-bromobutane
H3O+
O
O-HNH3
WWU-ChemistryWWU-Chemistry
Base-Promoted Hydrolysis of a Base-Promoted Hydrolysis of a Nitrile (Part One)Nitrile (Part One)
1)
:..
..
_
slow :.. _
:..
2)..
_:
..
:
+ H2O
:..
..+ OH
_
3):
..
..
:..
..
C N:R
CR
NH
OH
CR
NH2
O
C NR
O H
CR
N
OH
Tautomerism
O H
CR
NH
OH
WWU-ChemistryWWU-Chemistry
Base-Promoted Hydrolysis of a Base-Promoted Hydrolysis of a Nitrile (Part Two)Nitrile (Part Two)
4)
5)
6)
: :..
:..
..
_
O
CR NH2
O H
: :.. _
..
:..
R C NH2
O
O H
: :.. _
..
:..
R C NH2
O
O H
: :
:..
+ NH2:..
_O
CR
O H
O
CR OH
: :.... + NH2
:..
_O
CR O
: :.... :
_+ NH3
..
WWU-ChemistryWWU-Chemistry
Sect. 19.29: reduction of nitriles Sect. 19.29: reduction of nitriles with lithium aluminum hydride and with lithium aluminum hydride and
Hydrogen Hydrogen
C N
Nitrile
1) LiAlH4
2) H3O+
NH2
pentylamine
2 moles of H2 Palladium or Platinum
NH2
pentylamine
WWU-ChemistryWWU-Chemistry
The remaining sections will not be included on the third test.
WWU-ChemistryWWU-Chemistry
Sect. 19.30: Fats and oils Sect. 19.30: Fats and oils (Triglycerides)(Triglycerides)
CH2
C
CH2
HOCR
O C R
O C R
O
O
O
WWU-ChemistryWWU-Chemistry
The Fatty AcidsThe Fatty AcidsO
C OH(CH2)10CH3
O
C OH(CH2)12CH3
O
C OH(CH2)14CH3
O
C OH(CH2)16CH3 CH3 (CH2)7 CH CH (CH2)7 C OH
O
CH CH (CH2)7 C OH
O
CH2CHCHCH3 (CH2)4
CH CH (CH2)7 C OH
O
CH2CHCHCHCHCH2CH3
Lauric acid Myristic acid Palmitic acid
Stearic acid Oleic acid
Linoleic acid
Linolenic acid
WWU-ChemistryWWU-Chemistry
Sect. 19.31, 19.33, 19.34Sect. 19.31, 19.33, 19.34
• soaps
• proteins
• condensation polymers
WWU-ChemistryWWU-Chemistry
Wallace Carothers- commercialized Wallace Carothers- commercialized Nylon at DuPontNylon at DuPont
Source: Michigan State University, Department of Chemistryhttp://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml
WWU-ChemistryWWU-Chemistry
Functional Group InterconversionsFunctional Group InterconversionsR C N
R C OH
O
R C O
O
R' R C O
O
R C Cl
O
R C NH2
O
RC
O
R C O
O
R C NR'2
O
H2O
SOCl2
NH3
NR’2H
OH-
R’OH
RCOOH
H2O
NH3
NR’2HRCOOH
R’OH OH-
H2O
H2O
NH3
NR’2H
NH3
NR’2H