carboxylic acid and derivatives - NDSUcook.chem.ndsu.nodak.edu/chem342/chem342_09/files/... ·...

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R R O aldehydes ketones R X O carboxylic acid and derivatives Carbonyl Chemistry Wednesday, April 29, 2009

Transcript of carboxylic acid and derivatives - NDSUcook.chem.ndsu.nodak.edu/chem342/chem342_09/files/... ·...

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R R

O

aldehydesketones

R X

O

carboxylic acidand derivatives

Carbonyl Chemistry

Wednesday, April 29, 2009

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R R

O

R R

OElectrophiles (eg. H+)

Nucleophiles (eg. CH3MgBr)

O

OH

H

BaseO

O

an enolate

Wednesday, April 29, 2009

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O

α

β

O

α

β

O

α

β

O1

2 34

Nuc-H1

2 34

OH Nuc

O1

2 34

1

2 34

NucOH O1

2 34

Nuctautomerize

1,2-addition

1,4-addition (conjugate addition)

Nuc-H

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1,4-addition

OCH3NH2

O

NHCH3

1,4-addition

O O

Ph

1) Ph2CuLi2) H3O+

1,2-addition

O 1) PhMgBr2) H3O+ HO Ph

1,2-addition

O 1) PhLi2) H3O+ HO Ph

1,2-addition

O 1) NaBH42) H3O+ HO H

1,2-addition

O 1) LiAlH42) H3O+ HO H

Wednesday, April 29, 2009

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O

a hemiacetal

+ ROH2H+

HO OR

an acetal

RO OR

(+ ROH) (+ ROH)(- H2O)

O HA

Mechanism for Acetal Formation

OH

OHR

O OHR

H A O OR

H

Hemiacetal-H2O

OR

OR

resonance structures

HA

O OR

H

RAO O

RR

OH

resonance structures

HO R

NEED TO KNOW MECHANISM

O OR

H

H

Wednesday, April 29, 2009

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Wittig Reaction

+ Ph3P CH2

phosphoniumylide

+ Ph3P OO

Both aldehydes and ketones participate. The Wittig reagent is made from the alkyl halide by SN2 reactions.

O Ph3P+

Br

+ Ph3P:

PPh3O

+ Br

+ Ph3P:

easier to prepare Wittigreagent - substitution on a primary bromide.

Harder method

easier method

Wednesday, April 29, 2009

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R Y

O Nuc

R YO Nuc

R Nuc

O+ Y

Cl

O

Acid Halides(acetyl chloride)

O

Acid anhydrides(acetic anhydride)

OCH3

O

Esters(methyl acetate)

NH2

O

Amides(acetamide)

O

O

More Reactive Less Reactive

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R Y

O+ Nuc-H General NAS ReactionR Nuc

O+ HY

R Y

O+ HO-H HydrolysisR OH

O+ HY

R Y

O+ R'O-H AlcoholysisR OR'

O+ HY

R Y

O+ NH3 AminolysisR NH2

O+ HY

Wednesday, April 29, 2009

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R Y

O H-

R H

O+ Y-

R Y

O R'MgB r

R R'

O+ HY

ReductionH-

R'MgB r

R HO H

R R'O R' Grignard

R Cl

O R'2CuLi

R R'

O

R OCH3

O DIBAL

R H

O

Wednesday, April 29, 2009

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OH

OCH3

KMnO4

OH

OKMnO4 2

OH

O

OH

OH

O

H

O

Tollen's Oxidation

CrO3H3O+

Ag2ONH4OH

OH

OC H3O+

N

O

OMgBr

OH

O

H3O+

MgBr

O C OOH

OKMnO4 2

O

Oxidation Methods Other Methods

Wednesday, April 29, 2009

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R OH

O SOCl2

R Cl

O

R OH

O NaOH then CH3I

R OCH3

Olimited to primary alkyl halides

SN2

R OH

O HA, CH3OH

R OCH3

O

limited to inexpensive alcohol solvents -methanol and ethanol most practicalFischer Esterification

R OH

O LiAlH4

R OH

H H

then H3O+

R OH

O BH3

R OH

H H

then H3O+

selective for carboxylic acid reduction - will not react with esters

Carboxylic Acids

!

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R Cl

O H2O

R OH

O

R Cl

O R'CO2Na

R O

O

R Cl

O R'OH, pyridine

R OR'

O

R Cl

O R'NH2, pyridine

Acid Chlorides

+ HCl

R'

O+ NaCl

+ pyridine•HCl

+ pyridine•HClR NHR'

O

R Cl

O LiAlH4

R OH

H H

then H3O+

R Cl

O R'MgBr

R OH

R' R'

then H3O+

R Cl

O R'2CuLi

R R'

Adds Twice

Adds Twice

Adds OnceO

!

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Acid Anhydrides

O H2O

OH

O

R'OH, pyridine

R OR'

O

R'NH2, pyridine

LiAlH4

R OH

H H

then H3O+

+

+ pyridine•HO2CCH3

+R NHR'

O

R'MgBr

R OH

R' R'

then H3O+

Adds Twice

Adds Twice

HO

O

O

O

O

O

O

O

O

O

pyridine•HO2CCH3

O

O

O

O

O

O

!

Wednesday, April 29, 2009

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Esters

R

O H2O, NaOH

OH

O

LiAlH4

R OH

H H

then H3O+

+

R'MgBr

R OH

R' R'

then H3O+

Adds Twice

Adds Twice

OCH3

R

O

OCH3

R

O

OCH3

then H3O+

HOCH3

DIBAL

R H

Adds OnceO

R

O

OCH3then H3O+

!

Amides

R

O H2O, H3O+

OH

O

LiAlH4

R NH2

H H

then H3O+

Adds Twice - Nitrogen is retained.

NH2

R

O

NH2

heat

!

Wednesday, April 29, 2009

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O

Acid Catalyzed Enol Equilibrium

OHHA OH OHH

A

O

Base Catalyzed Enol Equilibrium

OHOH O OH

HA

Wednesday, April 29, 2009

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O OHH+ Br Br OBr + HBr

OBr2

CH3CO2H

OBr pyridine

O

OH

OR

PBr3Br2

then H2OOH

OR

Br

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N LiO+

O+

LDAlithium

diisopropyl amide

N H

100%

O 1) LDA2) CH3I

OCH3

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OpKa = 20

OpKa = 9

O

OEt

OpKa =13

EtO

O

OEt

O

EtO

O NaOEt, EtOH

R BrOEt

O

EtO

O

R

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H3O+, Heat

HO

O

OEt

O

EtO

O

R

R + CO2

H3O+

O

O

HO

O

R

H Heat

HO

OH

R

-CO2

tautomerize

OpKa = 20

OpKa = 9

O

OEt

OpKa =13

EtO

O

Wednesday, April 29, 2009

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OEt

O NaOEtEtOH

+ Br

O CO2EtO

H3O+, Heat

+ CO2

O

Wednesday, April 29, 2009

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O HA

Mechanism for Acetal Formation

OH

OHR

O OHR

H A O OR

H

Hemiacetal-H2O

OR

OR

resonance structures

HA

O OR

H

RAO O

RR

OH

resonance structures

HO R

NEED TO KNOW MECHANISM

O OR

H

H

Wednesday, April 29, 2009

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H

Fischer Esterification

R OH

O HA

R OH

OH R'OH

R OH

HO OR'H

A

R OH

HO OR'

R OH

HO OR'

HA

R

HO OR'

R OR'

OH

R OR'

O A

NEED TO KNOW MECHANISM

Wednesday, April 29, 2009

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OCH3

O OH

OCH3

O OHOH

O

Base Catalyzed Hydrolysis (Saponification)

+ OCH3 O

O+ HOCH3

Rapid acid-base reaction takes place

Carboxylate is a thermodynamic sink and makes the reaction essentiall non-reversible. To get the carboxylic acid, add acid to protonate.

OCH3

O HA

OCH3

OH

OCH3

OH H2O

OCH3

OH OH

H AOCH3

OH O H

HA

OCH3

OH O H

HOH

OH

OH

OH

OH

O A

Acid Catalyzed Hydrolysis

NEED TO KNOW MECHANISMS

BEST METHOD

- HOCH3

Wednesday, April 29, 2009

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NH2

O HA

NH2

OH

NH2

OH H2O

NH2

OH OH

H ANH2

OH O H

HA

NH2

OH O H

HOH

OH

OH

OH

OH

O A

Acid Catalyzed Hydrolysis

NEED TO KNOW MECHANISMS

- NH3

R NH2

O

H2O R OH

OHA (cat)Amide Hydrolysis

Wednesday, April 29, 2009

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Wednesday, April 29, 2009