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Aldehydes and Ketones Structure and properties Nomenclature Synthesis (some review) Reactions (some review) Spectroscopy – mass spec, IR, NMR
Aldehydes and Ketones
Structure and propertiesNomenclature Synthesis (some review)Reactions (some review)Spectroscopy – mass spec, IR, NMR
Structure and properties
Aldehydes and ketones are the simplest carbonyl containing compounds. R R'
O
Structure and properties
The carbonyl carbon and oxygen are sp2 hybridized.
Structure and properties
The carbon oxygen double bond is very polarized. The dipole moments of aldehydes and ketones are larger than most alkyl halides and ether.
H CH3
O
H3C CH3
O
C HH
Cl
H
u = 2.7 D u = 2.9 D u = 1.9 D
The high polarization of the carbonyl is due to the electronegativity of oxygen and the separation of charge in the resonance form.
Structure and properties
The large polarization of the carbonyl functional group produces dipole-dipole interaction between the molecules of aldehydes and ketones.
London dispersion Dipole-Dipole Hydrogen bonding
Structure and properties
Hydrogen bonding does not occur between aldehyde and ketone molecules. Hydrogen bonding can occur with other molecules such as water, alcohols and amines.
Solubility
Soluble in alcohols. Lone pair of electrons on oxygen of
carbonyl can accept a hydrogen bond from O-H or N-H.
Acetone and acetaldehyde are miscible in water. Solubility does decrease with longer chain length (> 4-5 carbons).
Naming Ketones (IUPAC)
Replace -e with -one. Indicate the position of the carbonyl with a number. For diones, don’t drop the final –e. Just add –dione.
Number the chain so that carbonyl carbon has the lowest number.
For cyclic ketones the carbonyl carbon is assigned the number 1.
-CHO > RCOR > R-OH > R-NH2 > C=C > C=C
Naming Ketones (IUPAC)
CH3 C
O
CH
CH3
CH3
O
Br
CH3 C
O
CH
CH3
CH2OH
3-methyl-2-butanone3-methylbutan-2-one 3-bromocyclohexanone
4-hydroxy-3-methyl-2-butanone4-hydroxy-3-methylbutan-2-one
Naming Ketones (IUPAC)
O
CH3
O
Cl Cl O
O
OCH2CH3
Common Names for Ketones
Named as alkyl attachments to -C=O. Use Greek letters instead of numbers.
(alpha, beta and gamma)
CH3 C
O
CH
CH3
CH3 CH3CH C
O
CH
CH3
CH3
Br
methyl isopropyl ketone a-bromoethyl isopropyl ketone
Common Ketones to know:
Acetone methyl ethyl ketone (MEK)
CH3 CH3
O
CH3 CH2CH3
O
CH3
O
CH2CH3
O O
Acetophenone propiophenone benzophenone
Naming Aldehydes
IUPAC: Replace -e with -al. The aldehyde carbon is number 1. If -CHO is attached to a ring, use the
suffix -carbaldehyde.
Examples
CH3 CH2 CH
CH3
CH2 C H
O
CHO3-methylpentanal
2-cyclopentenecarbaldehydecyclopent-2-en-1-carbaldehyde
Examples
CHO
OHOHC
Cl Cl
CHO
Name as Substituent
On a molecule with a higher priority functional group, C=O is oxo- and -CHO is formyl.
Aldehyde priority is higher than ketone.
CH3 C CH
CH3
CH2 C H
OO
COOH
CHO
3-methyl-4-oxopentanal 3-formylbenzoic acid
Aldehyde Common Names
Use the common name of the acid. Drop -ic acid and add -aldehyde.
1 C: formic acid, formaldehyde 2 C’s: acetic acid, acetaldehyde 3 C’s: propionic acid, propionaldehyde 4 C’s: butyric acid, butyraldehyde.
CH3 CH
Br
CH2 C H
O -bromobutyraldehyde
3-bromobutanal
Common Aldehyde
H H
O
H3C H
O
CH3CH2 H
O
CH3CH2CH2 H
O
Formaldehyde acetaldehyde propionaldehyde butyraldehyde
CHO CHO
CH3
CHO
Benzaldehyde p-tolualdehyde 2-naphthaldehyde
Common Aldehyde
Common forms of aldehydes.Formalin is a 40% solution of formaldehyde in water.
There are two dry forms of formaldehyde the cyclic trimer trioxane and paraformaldehyde.
O
O
O
O O O On
Trioxane paraformaldehyde
Heating these materials convert them to formaldehyde.
IR Spectroscopy
Very strong C=O stretch around 1710 cm-1.
Conjugation lowers C=O frequency to 1685-1690 cm-1.
Ring strain raises frequency.(Cycolpentanone 1745 cm-1, cycolpropanone 1810 cm-1 )
Additional C-H stretch for aldehyde: two absorptions at 2710 cm-1 and 2810 cm-1.
NMR Spectroscopy
1H Aldehyde protons are in the δ 9-10 range.
CH3 adjacent to a carbonyl singlet at δ 2.1.
CH2 adjacent to a carbonyl give multiple peaks at δ 2.5.
NMR Spectroscopy
13C Carbonyl carbon singlet in the 175-210 ppm range.
Carbons alpha to the carbonyl are in the 30-40 ppm range.
1H NMR Spectroscopy
13C NMR Spectroscopy
Mass Spectroscopy
Mass Spectroscopy
Mass Spectroscopy
Industrial Importance
Acetone and methyl ethyl ketone are important solvents.
Formaldehyde used in polymers like Bakelite.
Flavorings and additives like vanilla, cinnamon, artificial butter.
Common aldehydes and Ketones
Synthesis Review
Oxidation 2 alcohol + Na2Cr2O7 ketone 1 alcohol + PCC aldehyde
Ozonolysis of alkenes.
Synthesis Review
2 alcohol + Na2Cr2O7 ketone
OH Na2Cr2O7 , H2SO4
or H2CrO4
or KMnO4
OH Na2Cr2O7 , H2SO4
or H2CrO4
or KMnO4
Synthesis Review
1 alcohol + PCC aldehyde
OH
OH
OH
N
HCrO3Cl-
Synthesis Review
Ozonolysis of alkenes.
Synthesis Review
Predict the products of the following reactions.
1) O3
2) (CH3)2S
Synthesis Review
Friedel-Crafts acylation of aromatic rings Acid chloride/AlCl3 + benzene
ketone
Gatterman-Koch CO + HCl + AlCl3/CuCl + benzene
benzaldehyde
Synthesis Review
Z
Z = H , halogen or donor group
1) R Cl
O
AlCl3
2) H2O
Z O Z
O
+
OCH3
1) H3C Cl
O
AlCl3
2) H2O
Predict the products.
Synthesis Review
Predict the products.
+
Z
HO
Z
H
O
Z = H , activating group
Z
CO, HCl, AlCl3 / CuCl
OCH3
OCH3
Br
CO, HCl, AlCl3 / CuCl
Synthesis Review
Hydration of alkyne Use HgSO4, H2SO4, H2O : a methyl ketone is
obtained with a terminal alkyne.
Use Sia2BH followed by H2O2 in NaOH for aldehyde.
Synthesis Review
Hydration of alkyne
CH3CH2CH2C CH
Hg2+ , H2SO4
H2OCH3CH2CH2CCH3
O
CH3CH2CH2C CCH3
Hg2+ , H2SO4
H2O
Predict the products.
Synthesis Review
Hydration of alkyne to an aldehyde
CH3CH2CH2C CH1) Sia2BH
2) H2O2 , NaOHCH3CH2CH2CH2C
O
H
Synthesis Using 1,3-Dithiane
Remove H+ with n-butyllithium.
• Alkylate with primary alkyl halide, then hydrolyze.
R-X is a primary halide or tosylate.
Ketones from 1,3-Dithiane
After the first alkylation, the second H can be removed using BuLi and the resulting anion react with another primary alkyl halide. Giving a ketone upon hydrolyze.
S S
CH3 CH2CH3
CH3BrS S
CH2CH3
_ CH3
C
O
CH2CH3H2O
H+, HgCl2
S S
H CH2CH3
BuLi
Examples of using 1,3-Dithiane
1) BuLi
S S 2) C6H5CH2Cl
3) H+ , HgCl2 , H2O
2) (CH3)2CHCH2Cl
3) H+ , HgCl2 , H2O
S S
1) BuLi
Ketones from Carboxylates
Organolithium compounds attack the carbonyl and form a dianion.
Neutralization with aqueous acid produces an unstable hydrate that loses water to form a ketone.
The reaction can be done by first treating with one eq. of LiOH followed by a alkyl/aryl lithium reagent. Consider what is happening in each step (mechanistically how does the reaction work?).
Ketones from Carboxylates
OH
O1) LiOH
2) CH3Li
3) H3O+
1) LiOH
2) C6H5Li
3) H3O+
OH
O
Ketones from Nitriles
A Grignard or organolithium reagent attacks the nitrile carbon.
The imine salt is then hydrolyzed to form a ketone.
CCH2CH3
OC
CH2CH3
N MgBr
ether
C N
+CH3CH2MgBr H3O+
CN
1) CH3Li
2) H3O+
CN2) H3O
+
1) C6H5Li
Aldehydes from Acid Chlorides
A mild reducing agent can reduce an acid chloride to an aldehyde.
CH3CH2CH2C
O
HLiAlH(O-t-Bu)3CH3CH2CH2C
O
Cl
What would happen if you used LAH?
Acid Chlorides are prepared by treating an acid with thionyl chloride (SOCl2).
Show the synthesis of benzaldehyde from toluene.
Ketones from Acid Chlorides
Treatment of an acid chloride with lithium dialkylcuprate (R2CuLi) can also be used to synthesize ketones.
CH3CH2CH2Li2CuI
(CH3CH2CH2)2CuLi
(CH3CH2CH2)2CuLi + CH3CH2C
O
Cl CH3CH2C
O
CH2CH2CH3
Reagent preparation:
Ketones from Acid Chlorides
How it the lithium reagent made?
CCL
O
CCl
O
(CH2=CHCH2)2CuLi
(C6H5CH2)2CuLi
Nucleophilic Addition
Note: The carbonyl carbon is an electrophilic center.
The addition of a nucleophile to the carbonyl carbon is the most common reaction of aldehydes and ketones.
Nucleophilic Addition
There two general types of addition reactions.
Strong nucleophiles attack the carbonyl carbon, forming an alkoxide ion. The resulting alkoxide is then protonated to give an alcohol. (see previous slide)
Weak nucleophiles attack a carbonyl if it has been protonated (acid conditions). Protonation of the carbonyl increases the reactivity of the carbonyl carbon toward nucleophilic attack. The final step is deprotonation of the nucleophile.
Nucleophilic Addition
Strong nucleophile addition.
If the carbonyl carbon becomes a stereo center in the product, both enantiomer are produced.
Weak nucleophile addition.
OH
R'NucR
H-NucO-
R'NucR
+ Nuc-
R R'
O
Base
R R'
OH
H+ OH
R'NucR
H-NucOH
R'NucR
H
R R'
O
Nucleophilic Addition
Grignard reactionGrignard reagents add to aldehydes to give secondary alcohols and
ketones to give tertiary alcohols. (one exception: CH2O)R X
Mg
etherR Mg X
"Grignard"
R Mg X1)R'CHO
RCHR'
OH
2) H3O+
2) H3O+
1)C6H5CHOR Mg X R
OH
Addition of Water hydration
In acid, water is the nucleophile. In base, hydroxide is the nucleophile. Aldehydes are more electrophilic since they have
fewer e--donating alkyl groups. (more reactive)
HC
O
H+ H2O C
H H
HOOH
K = 2000
CH3C
O
CH3
+ H2O CCH3 CH3
HOOH
K = 0.002
Classify the products?
Addition of Alcohols
The addition of alcohols to the carbonyl is similar to the addition of water.
Mechanism
The formation of acetals and ketals is acid catalyzed.
Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH.
The addition of a single alcohol produces a hemiacetal. Under the acidic reaction conditions water is loss, followed by addition of a second molecule of ROH forming the acetal.
All steps are equilibrium processes (reversible) .
Mechanism for Hemiacetal
The acid catalyst protonates the carbonyl. Alcohol (a weak nucleophile) then adds to the
carbonyl. Loss of H+ gives the hemiacetal.
Hemiacetal to Acetal
+
OCH3HO OCH3
H+
H+
HO OCH3
HOH+
OCH3CH3OOCH3CH3O
H
+
OCH3+
HOCH3
HOCH3
Cyclic Acetals
Formation of cyclic acetals is used as a way of protecting the carbonyl group from under going nucleophilic attack in subsequent reactions. The protecting group can be remove by treatment with dilute acid.
Cyclic acetals are made by reacting the aldehyde or ketone with a diol
O OCH2
CH2
+CH2 CH2
HO OH
O
H3O+
Sugars commonly exist as acetals or hemiacetals.
Acetals as Protecting Groups
Hydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones.
O
H
O
+ CH2CH2
OH OH
O
HO
O
H+
Selective Reaction of Ketone
React with strong nucleophile (base). Remove protective group.
HO
O
CH3OO
HO
O
CH3MgBr
H
CH3HO
O
H+ / H2O
Selective Reaction of aldehydes and Ketones
O
CH2CH2
OH
H
O
How could the following synthesis be done.
Addition of HCN
CN- adds to the carbonyl group to give cyanohydrin. The order of reactivity is: formaldehyde > aldehydes > ketones >>
bulky ketones.
CH3CH2C
O
CH3 + CCH3CH2 CH3
HOCN
HCN
The nitrile group can be convert to an acid group by acid hydrolysis.
CN
OH
CO2H
OHH+
α-hydroxy acid
Formation of Imines
The formation of an imine involves an initial nucleophilic attack by ammonia or a primary amine on the carbonyl carbon. Followed by subsequent loss of a water molecule.
The C=O becomes a C=N-R group where R= H, alkyl or aryl
“imine” also called a Schiff base when R is an alkyl group
C OH3C
Ph
H+
C OH3C
Ph
H H2N R
R N C
CH3
OH
Ph
H
H
H2OR N C
CH3
OH
PhH
+ H3O+
H+
R N C
CH3
PhH
R N C
CH3
OH
PhH
R N C
CH3
O
PhH
H
HR N C
CH3
PhH
H2OR N C
CH3
Ph
Important N-containing derivatives
Formation of N derivatives
O
O
NH2NHCONH2
H+
NH2OH
H+
Loss of water is acid catalyzed, but acid deactivates the nucleophiles. NH3 + H+ NH4
+ (not nucleophilic). Optimum pH is around 4.5.
Wittig Reaction
This reaction involves the nucleophilic addition of a phosphorus ylides to the carbonyl carbon.
The product of a Wittig reaction is an alkene.
Phosphorus Ylides
The ylide is prepared by first reacting triphenylphosphine with an unhindered alkyl halide (methyl or primary halide) to form a phosphonium salt.
Treatment with butyllithium then abstracts a hydrogen from the carbon attached to phosphorus to produce the ylide.
Ph3P + CH3CH2Br Ph3P CH2CH3
+ _Br
Ph3P CH2CH3
+_
Ph3P CHCH3BuLi
+
ylide
Mechanism for Wittig
The negative C on ylide attacks the positive C of carbonyl to form a betaine.
Oxygen combines with phosphine to form the phosphine oxide.
Ph3P O
C CCH3
Ph
H
H3C
Ph3P
CH
CH3
C
OCH3
Ph
_+Ph3P
CH
CH3
C
OCH3
Ph
+
Ph3P
CH
CH3
C
OCH3
PhC O
H3C
Ph
+
Ph3P CHCH3
_
Wittig Reaction
Purpose are synthetic route for the preparation of the following compounds.
CH2
Oxidation of Aldehydes
Aldehydes are easily oxidized to carboxylic acids.
Tollens Test
Tollens reagent is prepared by adding ammonia to a AgNO3 solution until the precipitate dissolves.
Addition of Tollens reagent to a solution containing an aldehyde results in the formation of a silver mirror.
R C
O
H + 2 + 3 + 2+ 4+Ag(NH3)2+ OH
_ H2O2 Ag R C
O
O_
NH3 H2O
R C
O
H + 2 + 3 + 2+ 4+Ag(NH3)2+ OH
_ H2O2 Ag R C
O
O_
NH3 H2O
Reduction Reagents
Sodium borohydride, NaBH4, reduces C=O, but not C=C.
Lithium aluminum hydride, LiAlH4, much stronger, difficult to handle.
Hydrogen gas with catalyst also reduces the C=C bond.
Catalytic Hydrogenation
Catalytic hydrogenation is widely used in industry.
Raney nickel, finely divided Ni powder saturated with hydrogen gas.
Pt and Rh also used as catalysts.
ORaney Ni
OH
H
Deoxygenation
Reduction of C=O to CH2
Two methods: Clemmensen reduction if molecule is stable in
hot acid. Wolff-Kishner reduction if molecule is stable in
very strong base.
Clemmensen Reduction
C
O
CH2CH3 Zn(Hg)
HCl, H2O
CH2CH2CH3
CH2 C
O
H HCl, H2O
Zn(Hg)CH2 CH3
Wolff-Kisher Reduction
Form hydrazone, then heat with strong base like KOH or potassium t-butoxide.
Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO.
CH2 C
O
HH2N NH2
CH2 C
NNH2
H KOHheat
CH2 CH3
