Download Organic Chemistry II Introduction

Organic Chemistry II
Aldehydes and Ketones
Dr. Ralph C. Gatrone
Department of Chemistry and Physics
Virginia State University
Spring, 2011
1
Chapter Objectives
• Nomenclature
• Preparation
• Reactions
• Spectroscopy
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Nomenclature
• Aldehydes
• Identify the alkane
• Parent alkane must contain the CHO
group
• CHO group C is numbered 1
• Replace the “e” with “al”
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Examples
O
1
4
1 H
O
H
4-butyloctanal
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3-phenylbutanal
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Nomenclature
• Aldehydes
• Aldehyde carbon is bonded to ring
• Suffix used is “carbaldehyde”
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Examples
O
O
H
benzenecarbaldehyde
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H
cis-2-methylcyclopentanecarbaldehyde
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Common Names
O
H
H
H
formaldehyde
valeraldehyde
O
O
H3C
H
acetaldehyde
O
H
acrolein
H
crotonaldehyde
O
CH3CH2
H
propionaldehyde
O
O
butyraldehyde
O
H
H
O
H benzaldehyde
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cinnamaldehyde
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Nomenclature
•
•
•
•
•
•
Ketones
Identify the alkane
Parent alkane
The longest chain containing the carbonyl group
The carbonyl C gets the lowest number possible
Replace the “e” with “one”
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Examples
O
3-heptanone
O
(E,E)-nona-5,7-dien-2-one
O
O
O
1,2-cyclohexandione
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2-cyclohexenone
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Nomenclature
• If present with another functional group
• Prefix “oxo” is used
O
O
4-oxohexanal
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Common Names
O
O
O
acetone
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acetophenone
benzophenone
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As a Substituent
• When R-C=O is used as a substituent
• Referred to as an acyl group
• Ending “yl” is used
O
O
acetyl
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benzoyl
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Preparation
• [O] of primary ROH
PCC/CH2Cl2
OH
O
• [H] of RCO2H
o
OH 1. DIBAH/toluene/-78 C
O
2. H3O+
O
• [O] of secondary ROH
OH
[O]
O
many reagents can be use
cost, scale, sensitivity to acid or base
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Preparation
• Ozonolysis of Alkenes
R
H
1. O3
2. Zn/HOAc
H
R
O
must have one H
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Hydration of Alkynes
• Hydration of terminal alkynes in the presence of
Hg2+ (catalyst)
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Preparation
From Organometallics
O
R
O
R2CuLi
R
Cl
R
R2CuLi from RLi and CuCl
O
R
O
R2Cd
Cl
R
R
R2Cd from RLi and CdCl2
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Preparation
• Friedal-Crafts Acylation
O
R
O
Cl
R
AlCl3
• Recall:
• Reaction does not occur
on deactivated rings
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Reactions
• Oxidation of Aldehydes
O
R
O
[O]
H
R
OH
• [O] = KMnO4/acid; hot HNO3, and CrO3/acid
• Ketones are generally inert to oxidation
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Reactions
O
O
-
+
• Resonance contribution
• Carbon is electrophilic
• Oxygen is nucleophilic
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Nucleophilic Addition
O
O
-
Nu
Nu:
• Provides a tetrahedral intermediate
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The Tetrahedral Intermediate
HA
R
R
O
R
R
OH
Nu
Nu
HA
R
R
OH
Nu
HA
H +
OH
R
R
-H2O
Nu
Nu
R
R
• Aldehydes are more reactive than ketones
• Consider several nucleophiles
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Nucleophile = Water
•
•
•
•
Product is a 1,1-diol, a gem-diol, a hydrate
Reaction is equilibrium process
Position of equilibrium depends upon structure
Reaction is readily reversible
O
R
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R
HO
OH
R
R
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Equilibrium Process
O
R
OH
H2O
R
H
H
OH
O
R
OH
H2O
R
R
R
OH
when R=R=H 99.9% hydrate
when R = R = CH3 99.9% carbonyl
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Nucleophile = Y in HY
• Reaction of C=O with H-Y, where Y is
•
electronegative, gives an addition product
Formation is readily reversible
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Nu = HCN
Cyanohydrin Formation
• HCN – very weak acid
–
–
–
–
pKa = 9.1
Equilibrium favors HCN
Availability of CN as nucleophile is reduced
Base catalysis favors cyanohydrin formation
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Uses of Cyanohydrins
• The nitrile group (CN) can be reduced with LiAlH4 to
yield a primary amine (RCH2NH2)
• Can be hydrolyzed by hot acid to yield a carboxylic acid
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Nucleophile = Organometallic Reagent
• Grignard reagent
• Effectively a carbanion
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Grignard Additions
O
R
MgX+
O
H
R
R'
MgX
OH
R
H
H3O+
R'
H
R'
secondary alcohol
O
R
O
R"
MgX
OH
R'
R"
R
R"
R
R'
MgX+
H3O+
R'
tertiary alcohol
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Nucleophile = Hydride
• Reduction of Carbonyl compounds
• Can use NaBH4 or LiAlH4
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Hydride Addition
•
•
•
•
Convert C=O to CH-OH
LiAlH4 and NaBH4 react as donors of hydride ion
Source of H-1 (not real but useful formally)
Protonation after addition yields the alcohol
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Nucleophile = Amine
Imine and Enamine Formation
• Amines – organic derivatives of ammonia
• Classified by number of substituents on N
..
N
H
H
H
ammonia
..
N
..
N
R
H
H
primary
R
..
N
R
H
secondary
R
R
R
tertiary
• Primary and Secondary amines react
• Tertiary amines do not react with carbonyls
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Imines and Enamines
• Requires an acid catalyst
• pH dependent reaction
• Reaction is slow at high and low pH
• At high pH – not enough acid to protonate
• At low pH – the amine is protonated
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Imine Formation is Reversible
• Drive reaction to right
– Add excess amine
– Remove water
• Dean Stark Trap
– Removes water
– Azeotrope formation
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Derivatives of Imines
• Hydroxylamine (NH2OH)
O
R
NOH
NH2OH
R'
H+
R
R'
oxime
• Hydrazine (NH2NH2)
O
R
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NH2NH2
R'
H+
NNH2
R
R'
hydrazone
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Uses of Oximes
• Beckmann rearrangement
• Synthesis of Nylon
NHOH
H+
H
N
O
Nylon
caprolactam
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Uses of Hydrazones
The Wolff–Kishner Reaction
• Reduction under basic conditions
• Ketone or Aldehyde into an alkane
• Originally carried out at high temperatures but
with dimethyl sulfoxide as solvent takes place
near room temperature
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Uses of Hydrazones
The Clemmensen Reduction
• Reduction under acidic conditions
NNH2
R
H
Zn(Hg)/HCl
H
R
• Provides alkane from Ketone/aldehyde
• Through Hydrazone
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Uses of Hydrazones
Reduction of Carbonyls
• Reduction under neutral conditions
– Tosylhydrazone
NaBH3CN
O
O
S
NNH2
TsNHN
O
H3C
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Nucleophile = Alcohol
• Two equivalents of ROH and acid catalyst
• Acetal formation
O
OR
ROH/H+
OR
H3O+
HO
O
OH
H+
O
O
H3O+
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Uses of Acetals
• Acetals can serve as protecting groups for aldehydes and
ketones
• It is convenient to use a diol, to form a cyclic acetal (the
reaction goes even more readily)
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Uses of Acetals
• Thioacetals
• Prepared in same manner as acetals
• Reduction under neutral conditions
SH
HS
Raney Ni
S
O
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acid
S
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Acetals and Hemiacetals
• Common in carbohydrate chemistry
CH2OH
O
HO
OH
H
H
OH
H
OH
CH2OH
D-Fructose
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O
OH
HO
OH
HOCH2
O
OH
+
HO
CH2OH
CH2OH
OH
PYRANOSE
72%
FURANOSE
28%
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Glucopyranoses
OH
OH
O
HO
HO
HO
O
OH
OH
HO
OH
OH
H
-D-Glucose
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H
-D-Glucose
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Glucose
 -D-glucopyranose
• mp = 146 oC and [] = +112.2o
 -D-glucopyranose
• mp = 148 - 155 oC and [] = +18.7o
• Dissolve either in water, mutarotation occurs
• Alpha become beta, beta becomes alpha
• Equilibrium mixture results (37:63 :)
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Some Phosphorus Chemistry
• Amines react with alkyl halides
– Quaternary ammonium salt
..
N
R
R
RX
R
R
R
N
+
R
X-
R
• Phosphines also react with alkyl halides
R
..
P
R
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R
RX
R
R
P
+
R
X-
R
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Phosphorus Chemistry
• Positive charge on P stabilizes negative charge that can
form on an alpha carbon (must have a H atom)
R
R
P
+
base
R
X-
CH2R
R
R
P
+
R
- CHR
an ylid
alpha carbon
• Ylides are nucleophilic
• React with carbonyl compounds
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Nucleophile = Phosphorus Ylide
The Wittig Reaction
O
R
R P
+
R
-
R
R
- CHR
an ylid
O + PR3
CHR
R
R
betaine
O
R
PR3
H
R
CHR
R
oxaphosphetane
R
CHR
+
R3P=O
• Extends carbon chain by one carbon atom
• Adds a double bond into system
• Known to be able to control stereochemistry of double
bond
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Nucleophile = Phosphorus Ylide
The Wittig Reaction
• Generally use triphenyl phosphine
• Triphenylphosphine oxide is very stable
•
thermodynamically
Formation of P=O releases energy
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Uses of the Wittig Reaction
• Can be used for monosubstituted, disubstituted, and
•
trisubstituted alkenes but not tetrasubstituted alkenes
For comparison, addition of CH3MgBr to cyclohexanone
and dehydration with, yields a mixture of two alkenes
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Brief Review
• Aldehydes and ketones react with Nu
• sp3 intermediate forms
• Intermediate may
– Reverse to give SM
– Accept proton to form addition product
– Eliminate water to form new Nu=C species
• If derivative of carboxylic acid, also may
O
R
O
Nu:
X
-
R
O
X
R
Nu
Nu
• See details of this chemistry in Chapter 16
• Elimination of X does not occur when X = H or R
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Consider Leaving Groups
• Hydroxide (HO-) is a poor leaving group
– Generally forms water in order to leave
• Hydride (H-) very poor leaving group
– An exception found in Cannizzaro Reaction
– Aldehydes with no alpha hydrogens react
gamma H
H alpha
H
H
beta
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O
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The Cannizzaro Reaction
• Cannizzaro observed reaction in strong basic media
• Td intermediate transfers hydride to another aldehyde
• REDOX reaction
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The Biological Analogue of the
Cannizzaro Reaction
• Enzymes catalyze the reduction of aldehydes and
•
ketones using NADH as the source of the equivalent of
HThe transfer resembles that in the Cannizzaro reaction
but the carbonyl of the acceptor is polarized by an acid
from the enzyme, lowering the energy barrier
Enzymes are chiral
and the reactions are
stereospecific. The
stereochemistry
depends on the
particular enzyme
involved.
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Conjugate Nucleophilic Addition to ,Unsaturated Aldehydes and Ketones
• A nucleophile can
add to the C=C
double bond of an
,-unsaturated
aldehyde or ketone
• conjugate addition,
or 1,4 addition
• The initial product is
a resonancestabilized enolate
ion, which is then
protonated
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Conjugate Addition
• Resonance explains conjugate addition
O
O
-
O
-
+
+
positive charge designates electrophilic site
• Certain Nu: will add in 1,2 manner
• Other Nu: add 1,4 manner
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Conjugate Addition of Amines
• Primary and secondary amines add 1.4 to , unsaturated aldehydes and ketones to yield amino aldehydes and ketones
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Conjugate Addition of Alkyl Groups:
Organocopper Reactions
• Reaction of an , -unsaturated ketone with a lithium
•
•
diorganocopper reagent gives 1,4 addition
Diorganocopper (Gilman) reagents from by reaction of 1
equivalent of cuprous iodide and 2 equivalents of
organolithium
1, 2, 3 alkyl, aryl and alkenyl groups react but not
alkynyl groups
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Other Additions
• Grignards add 1,2 and 1,4 to , -
unsaturated ketones
• Organo lithium reagents add 1,2 to , unsaturated ketones
• Cyanide ion adds 1,4 to , -unsaturated
ketones
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Summary of Reactions
• Aldehydes - from oxidative cleavage of alkenes, oxidation of 1°
•
•
•
•
•
•
•
•
•
alcohols, or partial reduction of esters
Ketones - from oxidative cleavage of alkenes, oxidation of 2° alcohols,
or by addition of diorganocopper or organocadmium reagents to acid
halides .
Aldehydes and ketones - reduced to yield 1° and 2° alcohols ,
respectively
React with Grignard reagents giving alcohols
Addition of HCN yields cyanohydrins
1° amines add to form imines, and 2° amines yield enamines
Reaction with hydrazine gives hydrazones
– Reduction of hydrazone in base yields an alkane
– Reduction of hydrazone in acid/Zn yields an alkane
Alcohols add to yield acetals
Phosphoranes add to aldehydes and ketones to give alkenes (the
Wittig)
-Unsaturated aldehydes and ketones are subject to conjugate
addition (1,4 addition)
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Infrared Spectroscopy
• C=O
• Strong absorption 1660 – 1770cm-1
• See next two spectra
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NMR Spectroscopy
• The aldehyde H resonates at 10d
• Coupling is observed with adjacent H
• J = 3Hz
• H adjacent to C=O are slightly deshielded
• Resonate near 2.0 to 2.3d
• Methyl ketones are distinctive (2.1d)
• See next spectrum
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NMR Spectroscopy
• C=O carbons resonate between 190 –
215d
• See next spectra
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Mass Spectrometry
• A g H leads to McClafferty rearrangement
• Positive charge remains with O fragment
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Mass Spectrometry
  cleavage is also observed
• See next spectrum
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