WWU-Chemistry Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Chapter 19.

WWU-ChemistryWWU-Chemistry

Carboxylic Acid Derivatives:Carboxylic Acid Derivatives:Nucleophilic Acyl SubstitutionNucleophilic Acyl Substitution

Chapter 19


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!


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


The addition/elimination The addition/elimination mechanismmechanism


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


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!


CH3 C O CH2 CH3

O

Acid part of ester Alcohol part of ester


CH3 C O CH2 CH3

O

Ethyl ethanoate (IUPAC)

Ethyl acetate (common)


Methyl 2-methylpropanoate

CH3 CH C O CH3

CH3

O


Ethyl pentanoate

CH3 CH2 CH2 CH2 C O CH2 CH3

O


Methyl cyclohexanecarboxylate

H

C

OCH3

O


Isopropyl benzoate or 2-methylethyl benzoate

C O

O

CH CH3

CH3


Br

OEt

O

12

34

5

6

Ethyl 5-bromo-3,4-dimethylhexanoate


Br

OEt

O

12

3

4

56

Ethyl 5-bromo-3,4-dimethyl-2,4-hexadienoate


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!


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


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!!!!


Preparation of an EsterPreparation of an Ester

CR

O

Cl OHR

CR

O

O H-ClR

acid chloride alcohol ester


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


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


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!


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!


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)


Sect. 19.11: skipSect. 19.11: skip


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


Sect. 19.13 and 9.14: EstersSect. 19.13 and 9.14: Esters


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


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


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


Sect. 19.15 and 19.16 -- skipSect. 19.15 and 19.16 -- skip


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




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


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


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


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




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


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


Amides, continuedAmides, continued

• Keep this section simple, skip the DCC stuff


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


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


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)


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


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


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

..


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


The remaining sections will not be included on the third test.


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


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


Sect. 19.31, 19.33, 19.34Sect. 19.31, 19.33, 19.34

• soaps

• proteins

• condensation polymers


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


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

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WWU-Chemistry Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Chapter 19.

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