Download Chapter 19 Lecture

Aldehydes - IR
Aldehydes, Ketones - MS
Aldehydes -
1H-NMR
C9H10O - IR at 1690 cm-1
C9H10O isomer - IR at 1730 cm-1
C4H7ClO - IR at 1715 cm-1
C7H14O - IR at 1710 cm-1
C9H10O2 - IR at 1695 cm-1
C10H12O - IR at 1710 cm-1
C6H12O3 - IR at 1715 cm-1
C4H6O - IR at 1690 cm-1
Preparative methodology for aldehydes.
"something"
aldehyde
1° alcohol
O
H3O+
PCC
OH
H
O
From alkenes
1. B2H6 / THF
2. H2O2 / OH-
OH
CrO3
H
H
N
O
Br
From halides
1. Mg / ether
OH
PCC
2. CH2O / H3O+
H
+ 1 Carbon
OH
Br
1. Mg / ether
H
CrO3
2. oxirane / H3O+
O
N
+ 2 Carbons
Preparative methodology for ketones.
"something"
ketone
2° alcohol
H3O+
OH
CrO3
O
H3O+
From alkenes
Na2Cr2O7
1. Hg(OAc)2 /H2O
OH
2. NaBH4
O
H3O+
O
HgSO4 / H3O+
From alkynes
From halides
Br
Mg+Br-
O
Mg / ether
+
2. H3O
OH
CrO3
H3O+
O
+ 2 Carbons
Oxidation of aldehydes; ketones do not oxidize.
O
O
Ag2O / NH3
H
OH
OH-
Tollen's Reagent
OH
H
Ag2O / NH3
OH-
O
O
O
O
H3CO
H
Cu2+ / OH-
H3CO
OH
Fehling's Reagent
O
Mild permanganate
oxidation
H
O
MnO4- / H3O+
OH
Reaction Scheme for the Carbonyl Group Reacting as
an Electrophile with Nucleophiles
Reaction Scheme for the Carbonyl Group Reacting as
a Nucleophile with Electrophiles
Summary of H-centered nucleophiles in 1,2-additions
to C=O groups.
Nucleophile
BH4
-
AlH4
-
[ (CH3)2CHCH 2 ]2AlH
Reaction Conditions
Reaction mode
(Purpose)
1. NaBH4 / OH2. H 3O+
Intermolecular 1,2-addition
(reduction of aldehyde s and
ketones; synth esis of alcohols)
1. LiAlH4 / THF
2. H 3O+
Intermolecular 1,2-addition
(reduction of aldehyde s,
ketones and esters;
synthe sis of alcohols)
1. [(CH3)2CHCH 2]2AlH
in THF
2. H 3O+
Intramolecular 1,2-addition
(reduction of aldehyde s,
ketones and acyl halides;
synthe sis of alcohols
and aldehyde s)
H2
H2 / (Me/C)
Me = Pd, Pt, Ni
Intermolecular 1,2-addition
(reduction of aldehyde s,
ketones and esters;
synthe sis of alcohols
and alkane s)
H2
Zn/Hg amalgam
in HCl
Clemensen Reduction
(reduction of aryl ketones to
alkyl aromatic compound s)
For both the BH4- and AlH4- anions the stoichiometry is 4:1 in the substrate.
H
O
H
H
H
Al- H
AlH
+
O
H
H
H
H
AlH
O
O
+ 3 more mol
AlR4-
R
=
H
OH
AlR4
-
H3O+
H
+
H3AlO3
H
Reducing agents are selective for different functional groups.
HOH2C
CH2OH
H2 Pd/C
O
O
BH4-
LiAH
O
O
H
HOH2C
O
CH2OH
CH2OH
Ester functional group is first reduced to an aldehyde, then to alcohol.
H
O
H
H
H
Al- H
+
O
AlH
H
O
O
H
H
H
AlH
O
O
H
+
H
O
H
H
Al- OCH3
H
O
HOH2C
H
4 mol
AlH4H3O+
4 mol
+
H3AlO3
Because the R2AlH is a Lewis Acid the reaction is intramolecular.
H
H
Al
O
AlO
+
O
O
Al
Al-
H
H
O
H
Al
H3O+
HO
H
Summary of N-centered nucleophiles in 1,2- and 1,4-additions
to C=O groups.
Nucleophile
Reaction Conditions
Reaction mode
(Purpose)
NH3
1. NH 3 / H3O+
2. H 2 / Ni
RNH2
1. RNH 2 / H3O+
2. H 2 / Ni
Intermolecular 1,2-addition
(reductive amination;
synthe sis of imines
and 1° amines)
Intermolecular 1,2-addition
(reductive amination;
synthe sis of Schiff bases
and 2° amines)
RNH 2 / ethanol
Intermolecular 1,4-addition
(synthe sis of -aminocarbonyl
compounds )
R2 NH
R2NH / H3O+
Intramolecular 1,2-addition
(synthe sis of enamines)
N2H4
1. N 2H4 / H3O+
2. OH - / DMSO
Intermolecular 1,2-addition
(Wolff-Kishner reduction of
aldehyde s, ketones;
synthe sis of hyd razones, alkane s
and alkyl benzene s)
and d eriva t ives
Preparation of imines, Schiff bases, and 1°, 2° and 3° amines.
H
H
H2
NH3
O
H3O+
N
NH2
Ni
H
Imine
1° Amine
CH3NH2
H2
H3O+
Ni
O
N
H
N
Schiff Base
2° Amine
(CH3)2NH
H3O+
O
N
N
H
Enamine, 3° Amine
Example of the use of 1,4-addition in synthesis of complex amines.
O
HN
Br
N
H
O
O
O
Br
OH- / MeOH
N
CH3NH2
CH3NH2
ethanol
H3O+
N
H
N
H
H2
Ni
HN
N
H
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2additions.
Intrachain
O
Hal
Nu1,4
O
elimination
Nu1,4
OH
Nu1,2
1,2-addition
Nu1,4
1,4-addition
Nu1,2
Nu1,4
X
elaboration
Nu1,2
O
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2additions.
Exo-ring.
O
O
elimination
O
1,4-addition
Nu1,4
Hal
OH
1,2-addition
Nu1,4
Nu1,2
Nu1,2
Nu1,4
X
elaboration
Nu1,4
Nu1,2
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2additions.
Endo-ring.
Nu1,4
Hal
elimination
1,4-addition
O
O
O
Nu1,4
Nu1,2
Nu1,4
OH
1,2-addition
elaboration
Nu1,2
X
Nu1,4
Nu1,2
Examples closely following the templates - one elaboration step.
H2N
3
N
Br
O
3
1
HN
N
3
O
1
O
H
1
H
Examples closely following the templates - multiple elaboration steps.
O
Br
3
3
1
N
1
N
H
N
O
3
1
Br
H
OH
Use of 1,3-template for inducing multiple Hoffman eliminations.
NH2
1
1
1
3
3
NH2
O
3
1
1
Br
3
3
O
NH2
O
Use of 1,3-template for making fused rings via Michael Addition.
3
N
1
3
1
N
TmsO
Cl
1
3
N
TmsO
O
O
-O
3
3
1
O
Br
O
1
3
O
+
1
N
Summary of O-centered nucleophiles in 1,2-additions
to C=O groups.
Nucleophile
Reaction Conditions
H2 O
H3O+
or
OHROH / H3O+
ROH
excess ROH / H3O+
1,2 - or 1 ,3- diols
diol / H3O+
aldehy de or keto ne
polyo ls
equilibrium in H2O
Reaction mode
(Purpose)
Intermolecular 1,2-addition
(hydration)
Intermolecular 1,2-addition
(synthe sis of hemiacetals
and hemiketals)
(synthe sis of acetals and ketals)
Intramolecular 1,2-addition
(synthe sis of cyclic acetals
and ketals;
protecting group for aldehyde s
and ketones)
Intramolecular 1,2-addition
(cyclic carbohyd rates)
Hydration equilibrium favors the carbonyl compound for both steric
electronic (inductive) reasons).
OH
O
H3C
H2O
H3C
CH3
CH3
OH
However, sterically incongested carbonyls with electron-withdrawing
substituents favor hydrates.
OH
O
H
H2O
H
OH
OH
O
Cl3C
H
H
H2O
H
Chloral
Cl3C
H
OH
Chloral hydrate
The most important applications of acetals and ketals is in a concept
of C=O protecting groups using diols.
O
O
H
H
CH2OH
Br
O
O
Protecting
Reaction
H3O
+
OH
Br
Br
Br
H
O
2. CH2O / H3O+
O
HOH2C
H
H2O
use excess diol
1. Mg / ether
O
+
O
H
O
C=O-sensitive
Reaction(s)
OH
+
H
O
O
De-protecting
Reaction
O
H3O+
H
OH
use excess water
HOH2C
H
+
CH2OH
OH
Another important applications of acetals and ketals is in the
chemistry of carbohydrates and their polymers.
O
H
H
OH
Fisher projection formula for D- HO
glucose
H
H
OH
H
OH
CH2OH
CH2OH
CH2OH
O
OH
H
OH
H
H
H
H
OH
OH
H
OH
H
H
H
H
OH
OH
O
OH
Another important applications of acetals and ketals is in the
chemistry of carbohydrates and their polymers.
CH2OH
H
OH
OH
H
Cyclic Hemiacetal
formed from "top"
H
H
O
H
H
HO
HO
OH
H
OH
OH
OH
H
O
H
H
H
OH
H
OH
- or axial epimer
CH2OH
H
CH2OH
OH
H
O
O
H
H
H
H
H
HOH2C
OH
OH
H
OH
HO
HO
H
OH
OH
OH
OH
H
O
OH
H
H
H
OH
H
H
- or axial epimer
H
HOH2C
Polymer of all cyclic
-hemiacetal "
H
HOH2C
H
OH
H
OH
Cyclic Hemiacetal
formed from "bottom"
CH2OH
O
H
HOH2C
H
O
HO
H
H
HOH2C
O
O
HO
H
H
H
O
O
HO
OH
H
HOH2C
H
H
H
OH
H
O
O
HO
H
H
H
OH
HO
OH
H
H
H
OH
H
Summary of C-centered nucleophiles in 1,2- and 1,4-additions
to C=O groups.
Nucleophile
CN
-
R–
(R = alkyl, allyl, vinyl,
acetynyl and aryl)
Reaction Conditions
Reaction mode
(Purpose)
KCN / HCN
Intermolecular 1,2-addition
(formation of cyanohyd rins and
-hyd roxy and -amino acids)
1. RMg+Br- / ether
2. H3O+
Intermolecular 1,2-addition
(Grignard syn thesis of alcohols)
RCu
(R = alkyl, allyl, vinyl
and aryl)
1. RCu-Li+ / ether
2. H3O+
Intermolecular 1,2and 1,4-addition
(Gilman synth esis of -alkyl,
-vinyl and -aryl ketones)
(Ph)3P+-CH-R
(R = alkyl or acylalkoxy)
(Ph)3P+-CH-R / THF
Intermolecular 1,2-addition
(Wittig synthe sis of E-alkenes
or Z--unsaturated carbonyl
compounds )
–
Base-catalyzed addition of CN- is used for the synthesis of different classes
of organic compounds.
OH
OH
O
HCN / KCN
H3O+
H
CN
H
H
CO2H
or OH-
-hydroxy acid
O
OH
OH
HCN / KCN
H3O+
H
H
CN
CO2H
or OH-
H
H3O+


NH3
NH2
CO2H
H
-unsaturated acid
OH
O
H
H3CO
-amino acid
HCN
H3CO
H
CN
CO2H
There are two types of ylides: stabilized and unstabilized. They yield alkenes with
select stereochemistry.
P
Ph3P : +
Ph3P : +
Ph3P+
Br
Ph3P
Br -
BuLi
Ph3P+
THF
unstabilized ylide
O
Br
OCH3
Br +
Ph3P
O
O
OHOCH3
Ph3P+
OCH3
stabilized ylide
There are two types of ylides: stabilized and unstabilized. They yield alkenes with
select stereochemistry.
Ph3P+
H
+
O
unstabilized ylide
(E)-1-cyclopentyl-4-methyl-2-pentene
O
Ph3P+
O
H
OCH3
+
OCH3
O
stabilized ylide
methyl (Z)-4-methyl-2-pentenoate
H3O+
O
OH
Organocupper (Gilman) reagents are organometallic compounds with either
the alkyl, vinyl or aryl nucleophilic C that react by 1,4-addition.
Br
Li
2 Li
pentane
+
LiBr
CuI
ether
Cu- Li+
dialkylcopper lithium (R2CuLi)
HO
O
O
CH3
1. CH3Mg+Br- / ether
1. R2CuLi / ether
2. H3O+
2. H3O+
1,2-addition product
1,4-addition product