Transcript Preparation of Aldehydes/Ketones

Aldehydes and Ketones
Nomenclature
Properties
Preparation
reactions of Aldehydes
and Ketones
Characteristic reactions of Aldehydes
and Ketones
Carbanion related reactions
Spectroscopy
Aldehydes and Ketones
Nomenclature
 IUPAC
 Common
Properties
Preparation of Aldehydes
and Ketones






Oxidation reactions
Hydrolysis of Geminal Dihalides
Hydration of Alkynes
Reactions with Acid Derivatives and
Nitriles
Reaction with Carboxylic Acids
Reaction with Thioacetals
Aldehydes/Ketones via
Oxidation Reactions
From Alcohols via PCC
 From Alkenes via Ozonolysis
 From Glycols via Periodic Acid Cleavage

RCH 2 OH
PCC
R
C H
O
R 2 CHOH
PCC
R
C
R
O
R'CH
CR 2
ozonolysis
R' C H + R
O
R'
R
C
OH
CH 2 OH
HIO 4
R
C
O
C
R
O
R' + H
C H
O
Hydrolysis of
Geminal Dihalides
Formation of Aldehydes or Ketones
R CH Cl 2
R 2CCl 2
H 2O
²
R
H 2O
²
R
C H + 2 HCl
O
C R + 2 HCl
O
Hydration of
Alkynes
 Markovnikov Addition
 Anti-Markovnikov Addition
H 2O/H2SO 4
R C CH
R C CH 2
HgSO 4
OH
R C CH
1. 9-BBN
-
2. H 2O 2/OH
RCH CH
OH
R C CH 3
O
R CH 2 C H
O
Reactions with Acid Halides
 Aldehydes
via Selective Reduction
 Lithium
tri-tert-butoxyaluminum hydride
 Rosenmund reduction
 Ketones
via Friedel-Crafts Acylation
 Ketones via reaction with Organometallics
 Gilman
reagent (organocuprates)
Aldehydes from Acid
Chlorides
 Lithium
tri-t-butoxyaluminum hydride
reduction
 Rosenmund reduction
R
C Cl
O
R
C Cl
O
LiAlH(O-t-bu) 3
ether
R
H 2 / Pd / S
BaSO 4
R
Rosenmund catalyst
C H
O
C H
O
Aldehydes from Esters and
Amides
Diisobutylaluminum hydride
(DIBAH or DIBAL-H)
O
R C OR'
or
O
R C NH 2
or
O
R C NHR'
or
O
R C NR 2 '
1. Diisobutylaluminum
hydride
2.
+
H3 O
O
R C H
Ketones via Friedel-Crafts
Acylation
R C Cl
O
R C O C R
O
O
AlCl3
benzene
AlCl3
benzene
C R + HCl
O
C R + RCOOH
O
Ketones via Reaction
with Organometallics
Use of Lithium dialkylcuprates
R
C Cl
O
(R') 2CuLi
R
C R' + R'-Cu + LiCl
O
where R' can be alkyl, aryl, or vinyl
Reactions with Nitriles


Grignard Addition to give Ketones
DIBAH Addition to give Aldehydes
R CN
R'MgX
R
C N MgX
R'
R CN
DIBAH or DIBAL-H
diisobutylaluminum hydride
R
C H
O
R
+
H
H 2O
C R'
O
C N Al(i-bu)2
H
+
R
H /H2O
Ketones from Carboxylic Acids
Attack by Alkyl Lithium reagents
RLi
RCOOH
-
RCOO - Li+ RLi
R
R
R
R
R
R
C
C
O - Li+
-
H 2O
+
O Li
OH ( H O )
2
OH
+
RCOO Li + RH
R
R
R
C
C
O - Li+
-
O Li+
OH
OH
C R
O
Ketones from Thioacetals



Thioacetal formation from an aldehyde precursor
Alkylation of the thioacetal intermediate using alkyl
lithium reagents
Hydrolysis of the alkylated thioacetal to give ketone
product
R
C
H
R
S
C
C 4H 9Li
(
R
H
S
S
C 4H 1 0 )
C
R
CH 2 R'
S
S
C
+
Li
(a thioacetal)
H
R'C H 2X
R
HgCl 2 / CH3OH / H2O
(
S
C
BF 3
O
S
S
HSCH 2CH 2SH
HSCH 2CH 2 SH )
S
+ LiX
C
R
R
S
C
O
CH 2 R'
CH 2 R'
Characteristic Reactions of
Aldehydes and Ketones
 Reduction
reactions
 Alcohol
formation
 Alkane formation
 Oxidation
reactions
 Nucleophilic addition reactions
 Grignard
additions to form alcohols
 Addition of water (hydration) to form gem-diols
 Addition of alcohols to form acetals/ketals
 Addition of HCN to form cyanohydrins
 Addition of ammonia and ammonia derivatives
Reduction Reactions of
Aldehydes and Ketones
Alcohol
formation
 Hydrogenation
 Hydride
Alkane
reduction
formation
R
C H
H 2 / Pt
R
O
LiAlH4
R C H
ether
O
 Clemmensen
R
reduction
 Wolff-Kishner
reduction
R
C H
O
C H
O
conc. HCl
Zn(Hg)
NH 2NH 2
-
OH / H2O
CH 2OH
H 2O
H
+
R
R
CH 3
R
CH 3
CH 2OH
Oxidation of Aldehydes
and Ketones
 Conversion
of Aldehydes to Carboxylic acids
 Oxidation of Aromatic Aldehydes/Ketones to
Benzoic acid derivatives
 Haloform reaction of methyl carbonyls
 Periodic acid cleavage of vicinal dials/diketones
Aldehyde / Ketone Oxidations
+
R
H or Ar
C
C
Ag(NH3)2
(Tollens reagent)
H
RCOOH
(ArCOOH)
O
O
C
H
O
KMnO 4 or K2Cr 2O 7
or
C
²
COOH
R
O
CH 3
C
R
-
X2
OH / H2O
HCX 3 + RCOO
O
R
C
C
O
O
H
HIO 4
RCOOH + HCOOH + HIO 3
Aldehyde / Ketone Nucleophilic
Addition Reactions
R
C
R'
O
H
H 2O
R"MgX
+
R
C
O
R
C
O
R
C
H or OH
R'
H 2O
C
O
R
-
R'
R
R' dry HCl
R''OH
R'
C
R
C
R'
R'
R
HCN
R'
C
OH
C
OH
gem diol
OH
R
OR"
R'
OH
CN
G
C
OR"
OR"
ketal
cyanohydrin
R
H 2N
R'
OH
hemiketal
O
R
R"
+
(-H 2 O)
R'
C
N
G
Carbanion Related Reactions

Aldol Condensation


Self vs. Crossed
Claisen Condensation
Self vs. Crossed
 Dieckmann cyclization




Reformatsky Reaction
Wittig Reaction
Carbanion
Alkylations/Acylations/Conjugate
Addition reactions
Aldol Condensations
Self
Condensation
Crossed Condensation
2 RCH 2 C H
-
OH or H
H R
+
RCH 2 C
O
OH
RCH 2 C H + R' C H
O
CH C H
O
-
OH or H
+
O
H R
R' C CH C H
OH
O
Claisen Condensations
 Self
vs. Crossed Condensation
 Dieckmann Condensation
2RCH 2 C OR'
O
RCH 2
R'O R'OH
RCH 2 C
O R
-
C OR' + R" C OR' R'O
R'OH
O
O
R'O C
(CH 2)4
O
R'O C
O
(CH 2)5
CH C OR' + R'OH
R" C
O
CH C OR' + R'OH
O R
O
-
C OR' R'O
R'OH
O
O
C
O
-
R'O
C OR'
R'OH
O
C
O
OR' + R'OH
O
OR' + R'OH
Reformatsky Reaction
R C H + Br CH 2 C OR'
O
O
R C R + Br CH 2 C OR'
O
O
1. Zn/ benzene
2. H3O
+
R
C CH 2 C OR'
OH
1. Zn/ benzene
2. H3O
H
+
O
R
R
C CH 2 C OR'
OH
O
Wittig Reaction
Phosphonium salt formation
Ylide formation
Alkene formation
RCH 2X +Ph3P
+
Ph3P
R'
C
O
SN2
CH 2R X
-
R'
+
CHR
PPh3
+
+
Ph3P
CH 2R X
phosphonium salt
NaH
+
Ph3P
-
CHR + NaX + H 2
ylide
(R') 2C CHR
O PPh3
oxaphosphatane
R'
R'
C
C
H
+ R
Ph3P O
alkene
+
triphenylphosphine oxide
Carbanion
Alkylation/Acylation/Conjugate Addition
Reactions
 Malonic
Ester Synthesis
 Acetoacetic Ester Synthesis
 Stork Enamine Synthesis
 Michael Addition / Conjugate
Addition
Malonic Ester Synthesis
Formation of alkylated acetic acid derivatives
C2H 5 O C CH 2
O
NaOC 2H 5
C OC2H 5
C2 H 5OH
O
+
Na
C2H 5 O C CH C OC2H 5
O
O
RCH 2X
CH 2R
C2H 5O C CH C OC2H 5
O
O
+
+
Na
C2H 5O C CH C OC2 H 5
O
O
CH 2R
C2H 5O C CH C OC2 H 5
O
O
H /H2O
CH 2R
strong heat
HO C CH C OH
O
O
CH 2R
HO C CH C OH
O
O
RCH 2 CH 2COOH + CO 2
Malonic Ester Synthesis

Acylation/Hydrolysis/Decarboxylation
Na+
NaOC 2H 5
C2H 5O C CH 2 C OC2H 5
C2H 5O C CH C OC2H 5
C2H 5OH
O
O
O
O
Na+
C2H 5O C CH C OC2H 5
O
O
O
R C X
(-NaX)
C2H 5O C CH C OC2H 5
O
O C
R
O
+
C2H 5O C CH C OC2H 5
O
O C
R
H /H2O
HO C CH C OH
O
O C
O
HO C CH C OH strong heat
O
O C
R
O
R
O
R C CH 3 + 2 CO 2
O
Acetoacetic Ester Synthesis
Formation of alkylated acetone derivatives
CH 3 C CH 2 C OC2 H 5
O
O
Na +
CH 3 C CH
O
C OC2H 5
O
CH 2R
CH 3 C CH
O
C2H 5 OH
RCH 2 X
(-NaX)
H /H2O
O
CH 3 C CH
C OH
O
C OC2H 5
O
O
CH 2R
CH 3 C CH
O
C OC2H 5
O
CH 2 R
CH 3 C CH
O
strong heat
(- CO 2 )
+
CH 3 C CH
+
C OC2H 5
CH 2R
O
NaOC 2 H 5
Na
C OH
O
CH 3 C CH 2 CH 2R
O
Acetoacetic Ester Synthesis
Formation of acylated acetone derivatives
CH 3 C CH 2 C OC2 H 5
O
O
Na
+
CH 3 C CH C OC2H 5
O
O
NaOC 2 H 5
C2H 5 OH
O
R C X
(-NaX)
Na
CH 3 C CH C OC2H 5
CH 3
O
O
O
O
R
CH 3
O C
C CH C OC2H 5
O
O
R
R
O C
H +/H2O
C CH C OC2 H 5
+
CH 3
O C
C CH C OH
O
O
R
CH 3
O C
strong heat
C CH C OH
(- CO 2 )
O
O
CH 3 C CH 2 C R
O
O
Stork Enamine Synthesis
Formation of Alkylated Aldehydes/Ketones
H
H
H OH
R' C C H
R' C C H +R 2 NH
NHR 2
O
R'
(-H 2 O )
C
(an aminol )
C
+
( H )
C H
R'
NR 2
C H
NR 2
CH 2 R"
R"CH 2 X
R'
SN 2
C
C H
NR 2
+
+
CH 2 R"
R'
C
C H
NR 2
+
C H
(an enamine)
(a disguised carbanion)
C
C
NR 2
+
R'
C H
NR 2
+
R'
+
hydrolysis
CH 2 R"
R'
C
C H + R 2 NH
O
Stork Enamine Synthesis
Formation of Acylated Aldehydes/Ketones
H
H OH
R' C C H
R' C C H +R 2 NH
NHR 2
+
(an aminol )
O
R'
C
C
H
(-H 2 O )
R'
C
H
R'
C
R" C X
C
R'
C
+
+
R'
C
R"
C
C
O
H
NR 2
+
hydrolysis
H
NR 2
NR 2
O
R'
H
(an enamine)
R"
H
C
NR 2
(a disguised carbanion)
O
O
C
C
H
( H+ )
+
C
C
NR 2
NR 2
R'
+
C
R"
C
C
O
H + R 2 NH
Conjugate Addition to
Unsaturated Systems
O
O
Nu +
C
Nu
C C
O
Nu
C
H
C C
+
C
C C
O
Nu
C
C C
H
-1
where Nu = CN , NH3 , RNH 2 , & R 2NH
Michael Addition
Michael Donors
CH (COOR) 2
Michael Acceptors Michael Product
RCH
CH
malonic ester
COOR
C R'
CH
O
CH
C
R'
C
(Michael donor)
 unsaturated ketone
C
R'
C
R'
O
RCH
CH
C
O
 unsaturated ester
RCH
R 2CuLi
CH
C N
 unsaturated nitrile
dialkyl cuprate
C
enamine
RCH
H 2O
OR'
 -diketone
C
C C
O
O
N
C
 unsaturated aldehyde
 -ketoester
CH
H
O
RCH
O
C
CH NO 2
 unsaturated nitroalkene
C
CH C
C
O
Michael Addition
Robinson Annulation
O
C O
C
C
H 3C
C
C
OR
C
-
O C
ROH
C
C
H 3C
O
O
C
C Michael
C product
O
Michael donor Michael acceptor
-
OR ROH
O
C
C
O
C
C
C
O
C
C
HO
H 2O
C
H 2C
O
C
C
C
O
O C
C
C
Aldol
H 2C
C
C
C
O
C
C
Direct vs. Conjugate Addition to
Unsaturated Carbonyl Systems
OH
C C C
+
H
O
direct addition
+ Nu
C C C
Nu
H+
H O
C C C
Nu
conjugate addition
Conjugate addition
NH 3 , RNH 2 , & R2 NH
-1
CN
R SH
R 2 CuLi
c arbanions
(Michael addition)
Direct addition
LiA lH4
RLi or A rLi
RMgX (subjectto
steric considerations)
Spectroscopy of
Aldehydes and
Ketones
 Mass
Spectrometry
 Infrared Spectroscopy
 Pmr Spectroscopy
 Cmr Spectroscopy