Organic Chemistry II Aldehydes and Ketones

Dr. Ralph C. Gatrone Department of Chemistry and Physics Virginia State University

Spring, 2011

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

4 1 H

1 H

4-butyloctanal

3-phenylbutanal

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Nomenclature
Aldehydes Aldehyde carbon is bonded to ring Suffix used is carbaldehyde

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Examples
O H O H

benzenecarbaldehyde

cis-2-methylcyclopentanecarbaldehyde

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Common Names
O H O H3C H acetaldehyde O H O CH3CH2
O

formaldehyde
O

valeraldehyde

acrolein

propionaldehyde

O H crotonaldehyde

butyraldehyde
H

O H H benzaldehyde 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 O

3-heptanone

(E,E)-nona-5,7-dien-2-one

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

4-oxohexanal

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Common Names
O O O

acetone

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

2. H3O+

[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 must have one H R O 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 Cl R2CuLi from RLi and CuCl O R Cl R2Cd from RLi and CdCl2 R2Cd R O R R2CuLi R O R

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Preparation
Friedal-Crafts Acylation
O R AlCl3 Cl O R

Recall: Reaction does not occur

on deactivated rings

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Reactions
Oxidation of Aldehydes
O R H [O] R O 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 Nu HA R R OH Nu HA R R OH Nu H + OH R R Nu

-H2O R

Nu 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 R

HO R

OH R

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Equilibrium Process
O R H H2O R OH OH H

O R R

H2O R

OH 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 (CN) 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 H R R' MgX R' O H H3O+ MgX+ R R' secondary alcohol OH H

O R R" R R' MgX

O R'

MgX+ R" H3O+ R

OH R" 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 R H primary H R H secondary .. N R R R tertiary .. N R

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 R' NH2OH H+ NOH R R' oxime

Hydrazine (NH2NH2)
O R R' NH2NH2 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 WolffKishner 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 Zn(Hg)/HCl H 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 H3C NNH2 O

TsNHN

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Nucleophile = Alcohol
Two equivalents of ROH and acid catalyst Acetal formation
O ROH/H+ H3O+ HO O OH H3O+
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OR OR

H+

O O

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
HS acid
SH

Raney Ni S

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Acetals and Hemiacetals

Common in carbohydrate chemistry
CH2OH O HO H H H OH OH CH2OH D-Fructose HO OH O OH OH HOCH2 O HO OH PYRANOSE 72% FURANOSE 28% OH CH2OH

CH2OH

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Glucopyranoses
OH HO HO OH H
-D-Glucose -D-Glucose

OH O OH HO HO

O OH H OH

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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
R .. N R R RX R R R N R + X-

Phosphines also react with alkyl halides

R .. P R R RX R R P R
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X-

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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 XR R P + R

CH2R

- 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 - CHR an ylid R R betaine + R R O + PR3 CHR R O PR3 CHR R CHR R H R oxaphosphetane

+
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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 Aldehydes and ketones react with Nu sp3 intermediate forms Intermediate may

Brief Review

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 X

Nu: R

X R

O 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 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 H The 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 + + positive charge designates electrophilic site O -

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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