Post on 31-Dec-2015
description
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" 1° alcohol aldehyde
H3O+
OHPCC
H
O
1. B2H6 / THF CrO3 H
O
2. H2O2 / OH-OH
H
N
Br1. Mg / ether PCC H
O
2. CH2O / H3O+
OH
+ 1 Carbon
Br1. Mg / ether
2. oxirane / H3O+
OH
CrO3
N
H
O
From alkenes
From halides
+ 2 Carbons
Preparative methodology for ketones.
"something" 2° alcohol ketone
H3O+
OH O
1. Hg(OAc)2 /H2ONa2Cr2O7
O2. NaBH4
OH
O
HgSO4 / H3O+
Br
Mg / ether
2. H3O+
Mg+Br-
O
From alkenes
From halides
+ 2 Carbons
CrO3
H3O+
H3O+
From alkynes
OHOCrO3
H3O+
Oxidation of aldehydes; ketones do not oxidize.
Ag2O / NH3OH
O
OH
O
MnO4- / H3O
+
H
O
Tollen's Reagent
Mild permanganateoxidation
H
O
OH-
Ag2O / NH3
OH-
OH
O
H3CO
O
H Cu2+ / OH- H3CO
O
OHFehling's Reagent
H
O
Reaction Scheme for the Carbonyl Group Reacting as an Electrophile with Nucleophiles
Reaction Scheme for the Carbonyl Group Reacting as a Nucleophile with Electrophiles
Nucleophile Reaction Conditions Reaction mode(Purpose)
BH4 - 1. NaBH4 / OH-
2. H3O+
Intermolecular 1,2-addition(reduction of aldehydes and
ketones; synthesis of alcohols)
AlH4 - 1. LiAlH4 / THF2. H3O
+
Intermolecular 1,2-addition(reduction of aldehydes,
ketones and esters;synthesis of alcohols)
[ (CH3)2CHCH2 ]2AlH1. [(CH3)2CHCH2]2AlH
in THF2. H3O
+
Intramolecular 1,2-addition(reduction of aldehydes,ketones and acyl halides;
synthesis of alcoholsand aldehydes)
H2
H2 / (Me/C)Me = Pd, Pt, Ni
Intermolecular 1,2-addition(reduction of aldehydes,
ketones and esters;synthesis of alcohols
and alkanes)
H2
Zn/Hg amalgamin HCl
Clemensen Reduction(reduction of aryl ketones toalkyl aromatic compounds)
Summary of H-centered nucleophiles in 1,2-additionsto C=O groups.
For both the BH4- and AlH4
- anions the stoichiometry is 4:1 in the substrate.
O
Al-
H
H
H
H+
OAl-
H
H
H
H
OAl-
H
H
H
H
OH
+ H3AlO3
H3O+
H
+ 3 more mol
O
AlR4-
HR =
AlR4-
Reducing agents are selective for different functional groups.
BH4- LiAH
H2 Pd/C
O H
O
O
O
O
CH2OH
HOH2C
CH2OH
HOH2C
CH2OH
Ester functional group is first reduced to an aldehyde, then to alcohol.
O
O
HOH2C
Al-
H
H
H
H+
O
OAl-
H
H
H
H
O
OAl-
H
H
H
HH
O
+ Al-
H
H
H
OCH3
H
O
AlH4-
4 mol 4 mol+ H3AlO3H3O
+
Because the R2AlH is a Lewis Acid the reaction is intramolecular.
O
Al
H
+
H3O+
O
Al-
H
OAl-
H
OAl
H
OAl
H
HO H
Nucleophile Reaction Conditions Reaction mode(Purpose)
NH31. NH3 / H3O
+
2. H2 / NiIntermolecular 1,2-addition
(reductive amination;synthesis of imines
and 1° amines)
RNH21. RNH2 / H3O
+
2. H2 / Ni
RNH2 / ethanol
Intermolecular 1,2-addition(reductive amination;
synthesis of Schiff basesand 2° amines)
Intermolecular 1,4-addition(synthesis of β-aminocarbonyl
compounds)
R2NH R2NH / H3O+ Intramolecular 1,2-addition
(synthesi sof enamines)
N2H4a nd derivatives
1. N2H4 / H3O+
2. OH- / DMSOIntermolecular 1,2-addition(Wol -ff Kishner reduction of
aldehydes, ketones;synthesi sof hydrazones, alkanes
and alkyl benzene)s
Summary of N-centered nucleophiles in 1,2- and 1,4-additionsto C=O groups.
O
H
O
CH3NH2
NH3
H3O+
H3O+
N
H
H
H2
Ni NH2
1° AmineImine
N
Schiff Base
H2
NiNH
2° Amine
O
(CH3)2NH
H3O+
N N
Enamine, 3° Amine
Preparation of imines, Schiff bases, and 1°, 2° and 3° amines.
H
Example of the use of 1,4-addition in synthesis of complex amines.
Br
O HN
NH
Br
O
OH- / MeOH
O
CH3NH2
ethanol
O
NH
CH3NH2
H3O+
N
NH
H2 Ni
HN
NH
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
O
Hal
eliminationO
1,4-addition
ONu1,4
1,2-addition
OHNu1,4
Nu1,2Nu1,4
Nu1,2 elaborationXNu1,4
Nu1,2
Intrachain
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
O
Hal
elimination O1,4-addition
O
Nu1,4
1,2-addition
OH
Nu1,4
Nu1,2
Nu1,4
Nu1,2 elaboration
Exo-ring.
X
Nu1,4Nu1,2
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
Various templates for 1,3-difunctionalized compounds via 1,4- and 1,2-additions.
O
elimination
O
Hal1,4-addition
O
Nu1,4
OH
Nu1,4
Nu1,2
Nu1,4
1,2-addition
Nu1,2
elaboration
X
Nu1,4
Nu1,2
Endo-ring.
H2N
HN
N
HO
Br
H
O
NO
13
1
3
1
3
Examples closely following the templates - one elaboration step.
N
N
H
Br
Br
H
N
O
13
13
1
3
Examples closely following the templates - multiple elaboration steps.
OH
O
O
Br
O
O
NH2
NH2
NH2
Use of 1,3-template for inducing multiple Hoffman eliminations.
1
3
1 1
11
3 3
33
OBr
Use of 1,3-template for making fused rings via Michael Addition.
1
111
3
33 3
O O N
Tms O N
-O
+13
Tms O
N
O
13
Cl
N
O
Nucleophile Reaction Conditions Reaction mode(Purpose)
H2O
H3O+
orOH-
Intermolecular 1,2-addition(hydration)
ROH
ROH / H3O+
excess ROH / H3O+
Intermolecular 1,2-addition(synthesis of hemiacetals
and hemiketals)
(synthesis of acetals and ketals)
1,2- or 1,3-diols diol / H3O+
Intramolecular 1,2-addition(synthesis of cyclic acetals
and ketals;protecting group for aldehydes
and ketones)
aldehyde or ketonepolyols equilibrium in H2O Intramolecular 1,2-addition
(cyclic carbohydrates)
Summary of O-centered nucleophiles in 1,2-additionsto C=O groups.
Hydration equilibrium favors the carbonyl compound for both stericelectronic (inductive) reasons).
OH
H3CCH3
OHH3C
O
CH3
H2O
However, sterically incongested carbonyls with electron-withdrawingsubstituents favor hydrates.
OH
HH
OHH
O
H
H2O
OH
Cl3CH
OHCl3C
O
H
H2O
ChloralChloral hydrate
The most important applications of acetals and ketals is in a conceptof C=O protecting groups using diols.
O
H
H3O+
Br
O
H
CH2OH
O
HBrOH OH
+
HBr
O
O + H2O
1. Mg / ether
2. CH2O / H3O+
HBr
O
O
HHOH2C
O
O
HHOH2C
O
OH3O
+
O
H
CH2OHOH OH
+
use excess diol
use excess water
ProtectingReaction
C=O-sensitiveReaction(s)
De-protectingReaction
Another important applications of acetals and ketals is in thechemistry of carbohydrates and their polymers.
Fisher projection formula for D-glucose
OHH
OH
CH2OH
HOH
H
H
OH
H O
OHH
OH
CH2OH
H
OH
H
H
OH
O
H
H OH
HO H
H OH
H OH
CH2OH
O H
Another important applications of acetals and ketals is in thechemistry of carbohydrates and their polymers.
Cyclic Hemiacetal formed from "top"
OO
H
OH
CH2OH
HOH
H
H
OH
H
OH
H
HOHO
H
H
OH
H
OH
HOH2C
H
OO
H
OH
CH2OH
HOH
H
H
OH
OH
H
H
HOHO
H
OH
H
H
OH
HOH2C
H
OH
H
OH
CH2OH
HOH
H
H
OH
H O
α- or axial epimer
OHH
OH
CH2OH
HOH
H
H
OH
H
OCyclic Hemiacetal formed from " bottom"
β- or axial epimer
O
H
HOHO
H H
H
OH
HOH2C
H
O
H
HO
H
O
H
H
OH
HOH2C
H
O
H
HO
H H
H
OH
HOH2C
H
O
H
HO
H
OH
H
H
OH
HOH2C
H
OOPolymer of all cyclic
β-hemiacetal "
Nucleophile Reaction Conditions Reaction mode(Purpose)
CN - KCN / HCN Intermolecular 1,2-addition(formation of cyanohydrins andα-hydr oxyand α-amino acid )s
R –
( R= alkyl, ally , l vinyl,acetyny l an d ary )l
1. RMg+Br- / ether2. H3O
+
Intermolecular 1,2-addition(Grignard synthesis of alcohols)
RCu –
(R = alkyl, allyl, vinyland aryl)
1. RCu-Li + / ether2. H3O
+
Intermolecular 1,2-and 1,4-addition
(Gilman synthesis of β-alkyl,β-vinyl and β-aryl ketones)
(Ph)3P+-CH-R
(R = alkyl or acylalkoxy)(Ph)3P
+-CH-R / THF Intermolecular 1,2-addition(Wittig synthesis of E-alkenesor Z-α,β-unsaturated carbonyl
compounds)
Summary of C-centered nucleophiles in 1,2- and 1,4-additionsto C=O groups.
Base-catalyzed addition of CN- is used for the synthesis of different classesof organic compounds.
O
HHCN / KCN
OH
HCN
H3O+
or OH-
OH
HCO2H
α-hydroxy acid
O
H
OH
HCN
H3CO H3CO
HCN
O
HHCN / KCN
OH
HCN
H3O+
or OH-
OH
CO2HH
CO2H
NH2
CO2HH
H3O+
ΔNH3Δ
α,β-unsaturated acidα-amino acid
There are two types of ylides: stabilized and unstabilized. They yield alkenes withselect stereochemistry.
P Ph3P
Ph3P : + Br Ph3P+
Br -
BuLi
THF
Ph3P+
Ph3P : +OCH3
Br Ph3P+
Br -
OH-
O
OCH3
O
Ph3P+
OCH3
O
stabilized ylide
unstabilized ylide
There are two types of ylides: stabilized and unstabilized. They yield alkenes withselect stereochemistry.
Ph3P+
Ph3P+
OCH3
O
stabilized ylide
unstabilized ylide
+
O
H
(E)-1-cyclopentyl-4-methyl-2-pentene
+
O
HO
OCH3
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.
dialkylcopper lithium (R2CuLi)
+
Br
2 Li
pentane
Li
LiBr CuI
ether Cu-Li+
O
1. R2CuLi / ether
2. H3O+
O
1,4-addition product1. CH3Mg+Br- / ether
2. H3O+
HO CH3
1,2-addition product