Aldehydes and Aldehydes and Ketones. Ketones. Nucleophilic Nucleophilic Addition Addition to the to the Carbonyl Group Carbonyl Group
Aldehydes and Ketones.Aldehydes and Ketones.Nucleophilic AdditionNucleophilic Addition
to theto theCarbonyl GroupCarbonyl Group
C
O
R H C
O
R R
An aldehydeAn aldehyde A ketoneA ketone
C
C
C
C
CHO
OH
OH
OH
OH
CH2OH
H
H
H
H
RiboseRibose
CCH3
O
H
CH3
CH3
O
ProgresteroneProgresterone
IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes HH
OO OO
HH
OO HCCHCHHCCHCH
OO1) Base the name 1) Base the name on the chain that on the chain that contains the contains the carbonyl group and carbonyl group and replace the replace the -e-e ending of the ending of the hydrocarbon by hydrocarbon by -al-al..
4,4-dimethylpent4,4-dimethylpentananalal5-hex5-hexenenalal
2-phenylprop2-phenylpropaneanedialdial(keep the (keep the -e -e endingendingbefore before -dial-dial))
IUPAC Nomenclature of AldehydesIUPAC Nomenclature of Aldehydes
2. The aldehyde functional group has priority over 2. The aldehyde functional group has priority over -X, -OH, -OR, double and triple bonds.-X, -OH, -OR, double and triple bonds.
Name –OH as hydroxy substituentName –OH as hydroxy substituentName –OR as alkoxy substituentName –OR as alkoxy substituent
CHCH33CHCH22CCHCCH22CHCH22CHCH33
OOCHCH33CHCHCHCH22CCHCCH33
OO
CHCH33 HH33CC OO
1) Base the name on the 1) Base the name on the chain that contains the chain that contains the carbonyl group and replace carbonyl group and replace --ee by by -one-one. Number the chain . Number the chain in the direction that gives the in the direction that gives the lowest number to the lowest number to the carbonyl carbon.carbonyl carbon.
Substitutive IUPAC Nomenclature of KetonesSubstitutive IUPAC Nomenclature of Ketones
3-3-hexanhexanoneone
4-methylcyclohexan4-methylcyclohexanoneone
4-methyl4-methyl-2--2-pentanpentanoneone
Trivial name for common aldehydes and ketones Trivial name for common aldehydes and ketones are widely used. Aldehydes are named after the parent are widely used. Aldehydes are named after the parent carboxylic acids with –carboxylic acids with –oic acidoic acid or – or –ic acidic acid ending ending changed to –changed to –aldehydealdehyde. (Table). (Table)
Propanone is usually called acetone, while the Propanone is usually called acetone, while the other simple ketones are sometimes named by a other simple ketones are sometimes named by a functional-group name. The alkyl or aryl groups functional-group name. The alkyl or aryl groups attached to the carbonyl group are named, then the attached to the carbonyl group are named, then the word ketone is added.word ketone is added.
CH3CCH3
O
IUPAC: propanone
trivial: acetone
CH3CCH2CH3
O
butanonemethyl ethyl ketone
(CH3)2CHCCH2(CH3)3
O
2,2,4-trimethyl-3-pentanoneisopropyl tert-butyl ketone
Trivial names for some carboxylic acids and aldehydes
Carboxylic acid Aldehydes
HCOH
O
formic acid HCH
O
formaldehyde
CH3COH
O
acetic acid CH3CH
O
acetaldehyde
CH3CH2COH
O
propionic acid CH3CH2CH
O
propionaldehyde
CH3CH2CH2COH
O
butyric acid CH3CH2CH2CH
O
butyraldehyde
COH
O
benzoic acid CH
O
benzaldehyde
Other positions in a molecule in relation to the carbonyl Other positions in a molecule in relation to the carbonyl group may be referred to be Greek lettersgroup may be referred to be Greek letters
Preparation of aldehydePreparation of aldehyde
1. Oxidation of primary alcohols 1. Oxidation of primary alcohols
CHCH33CHCH22OH + CrOOH + CrO33.2.2 N CHCH33CHOCHO
EtanolEtanol Kromat piridin oksidaKromat piridin oksida EtanalEtanal
2. Reduction of acid derivates2. Reduction of acid derivates
RCOOHSOCl2
RCOCl RCHOH2/Pt
(H3C)2HC CH3 + CH3COClAlCl3
(H3C)2HC CH3
COCH3
Isopropil toluenaIsopropil toluena Asetil kloridaAsetil klorida 5-isopropil-2-metil5-isopropil-2-metilasetofenonasetofenon
3. From terminus of alkyne (hydroboration)3. From terminus of alkyne (hydroboration)
C CHR + Sia2BH CHR CH BSia2H2O2
OH-/H2ORCH2CHO
disiamilborandisiamilboran Vinyl boranVinyl boran
Preparation of KetonePreparation of Ketone
1. Friedel-Craft Acylation1. Friedel-Craft Acylation
ArH + RCOClAlCl3
ArCOR
2. Oxidation of secondary alcohol2. Oxidation of secondary alcohol
CH3CH(OH)CH3H2CrO4, H+
C
O
CH3H3C
3. From Alkyne3. From Alkyne
C CR RH3O+, Hg2+
H2ORCOCHR RCOCH2R
HidrationHidration
C CR R(1) (BH3)2
(2) H2O2, OH-RC(OH)=CHR RCOCH2R
HidroborationHidroboration
boiling pointboiling point
––6°C6°C
49°C49°C
97°C97°C
Aldehydes and ketones have higher boilingAldehydes and ketones have higher boilingthan alkenes, but lower boiling points than alcohols. than alkenes, but lower boiling points than alcohols.
More polar than alkenes, More polar than alkenes, but cannot form but cannot form intermolecular hydrogen intermolecular hydrogen bonds to other carbonyl bonds to other carbonyl groupsgroups
OO
OHOH
nucleophiles attack carbon; nucleophiles attack carbon; electrophiles attack oxygenelectrophiles attack oxygen
Resonance Description ofResonance Description ofCarbonyl GroupCarbonyl Group
CC
OO •••• ••••
CC
OO
++
––•••••••• ••••
Acid Catalyst Makes Carbon More Electrophilic
CC••••OO ••••
Step 1:Step 1:Step 1:Step 1:++ ••••
HH
OOHH
HH++
++
CC
••••OOHH++
•••• ••••
HH
OO
HH
CC••••OOHH••••++
Nucleophilic Nucleophilic
Addition to Carbonyl GroupsAddition to Carbonyl Groups Basic Reaction
CC••••OO ••••Nu:Nu:
••••
NuNu CC OO••••
••••
••••••••––
Ketones are Less Reactive Than Aldehydes
1. Steric Reasons
2. R Groups are more electron donating than H
Grignard reagents act as nucleophilesGrignard reagents act as nucleophilestoward the carbonyl grouptoward the carbonyl group
RR
MgXMgX
CC
OO••••
••••
–– ++
––
MgXMgX++
RR CC
OO••••
•••• ••••
diethyldiethyletherether
••••
RR CC
OHOH••••
HH33OO++
two-step sequence two-step sequence gives an alcohol as gives an alcohol as the isolated productthe isolated product
ExamplesExamples MgClMgCl CC OO
HH
HH
CCHH22OHOH
HH33OO2)2)++
CHCH33(CH(CH22))44CHCH22MgBrMgBr CC OO
HH33CC
HHCHCH33(CH(CH22))44CHCH22CCHHCHCH33
OHOH
++
2) H2) H33OO++
ExampleExample CC
OHOH
CHCH33
CHCH22CHCH33
CC CHCH22CHCH33
OO
CHCH33MgXMgX
There are two other There are two other possibilities. possibilities.
Can you see them?Can you see them?
HH22OO
Hydration of Aldehydes and KetonesHydration of Aldehydes and Ketones
CC••••OO ••••
HOHO CC OO HH••••
••••
••••
••••
compared to Hcompared to H
electronic: electronic: alkyl groups stabilize alkyl groups stabilize reactantsreactants
steric: steric: alkyl groups crowdalkyl groups crowdproductproduct
OHOH
OHOH
RR R'R'++ HH22OO CCCCRR R'R'
OO
Substituent Effects on Hydration EquilibriaSubstituent Effects on Hydration Equilibria
Mechanism of Hydration (acid)Mechanism of Hydration (acid)
Step 1: Acid CatalystStep 1: Acid CatalystStep 1: Acid CatalystStep 1: Acid Catalyst
CC••••OO•••• ++ ••••
HH
OOHH
HH++ ++
CC
••••OOHH++ •••• ••••
HHOO
HH
Step 2: Nucleophilic attackStep 2: Nucleophilic attackStep 2: Nucleophilic attackStep 2: Nucleophilic attack
CC••••OOHH++
++••••
HH
OO
HH
••••CC OOHH
••••
••••
HH
OO
HH
•••• ++
Mechanism of Hydration (acid)Mechanism of Hydration (acid)
Step 3: Regeneration of catalystStep 3: Regeneration of catalystStep 3: Regeneration of catalystStep 3: Regeneration of catalyst
++••••
HH
OO
HH
••••CC OOHH
••••
HHOO
HH
••••
•••• •••• OO
HH
••••CC OOHH
••••
••••
++
HH
HHOO
HH ••••
++
One Alcohol Will React with a Ketone to FormOne Alcohol Will React with a Ketone to Forma Hemiketal; Two Will Form a Ketala Hemiketal; Two Will Form a Ketal
R"OR"O CC OO HH••••
••••
••••
••••
RR
R'R'a a hemiketalhemiketal..
CC••••OO ••••
RR
R'R'
+ + R’’-OHR’’-OH
R"OR"O CC OROR••••
••••
••••
••••
RR
R'R'
+ H+ H22OO
A ketalA ketal
R"OR"O CC OO HH••••
••••
••••
••••
RR
R'R'
R-OHR-OH / /HH++
HClHCl
2CH2CH33CHCH22OOHH++
+ H+ H22OO
Benzaldehyde diethyl acetal (66%)Benzaldehyde diethyl acetal (66%)
ExampleExample
CHCH
OO CH(CH(OOCHCH22CHCH33))22
MechanismMechanism; ; Step 1: Protonate O of Carbonyl groupStep 1: Protonate O of Carbonyl group
HH
HH
RR++OO••••CC OO
••
••••••
CC OO••
••HH
RROO
••••HH
++ ••••++
Step 2: Nucleophilic atom (O) attacks electrophilic C.Step 2: Nucleophilic atom (O) attacks electrophilic C.
CC OO••••
HH
++
RR
HH
OO••••••••CC OO
••••OO
••••HH
++••••
RR
HH
CC OO••••
OO••••
HH++••••
RR
HH
OORR HH
••••••••
Step 3: H is abstracted to form hemiketal/hemiacetalStep 3: H is abstracted to form hemiketal/hemiacetal
++HH
OORR HH••••
CC OO••••
OO ••••
HH
••••RR
••••
Step 4: Hemiacteal/hemiketal is protonated to formStep 4: Hemiacteal/hemiketal is protonated to formA good leaving group (HA good leaving group (H22O)O)
CC OO••••
OO ••••
HH
••••RR
••••
HH
HH
RR++OO•••• CC OO
••••OO
HH
••••RR
••••
HH++ ++
HH
RR
OO••••••••
OO••••
OO
HH
••••RR
••••++
HH
CC
Step 5: Leaving group (HStep 5: Leaving group (H22O) leaves andO) leaves and
forms carbocationforms carbocation
Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage
CCOO••••
RR
•• ++ OO••••
HH
HH••••++••••
Carbocation is stabilized by delocalizationCarbocation is stabilized by delocalizationof unshared electron pair of oxygenof unshared electron pair of oxygen
CCOO••••
RR
••••++ CCOO
RR
••••
++
CCOO••••
RR
••••++ OO
••••
HH
RR••••
Step 6: Second nucleophile (ROH) attacks carbocationStep 6: Second nucleophile (ROH) attacks carbocation
Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage
CCOO••••
RR
••••++OO
••••
HH
RR
CCOO••••
RR
••••++OO
••••
HH
RR
OO••••
HH
RR••••
Step 7: Alcohol abstracts acidic H to form acetal/ketal.Step 7: Alcohol abstracts acidic H to form acetal/ketal.
++HH OO••••
HH
RRCCOO••••RR
••
••
OO••••
RR
••••
Hemiacetal/hemiketal-to-acetal/ketal StageHemiacetal/hemiketal-to-acetal/ketal Stage
CCOO••••
RR
••••++OO
••••
HH
RR
OO••••
HH
RR••••
Step 7: Alcohol abstracts acidic H to form acetal/ketal.Step 7: Alcohol abstracts acidic H to form acetal/ketal.
++HH OO••••
HH
RRCCOO••••RR
••
••
OO••••
RR
••••
CCRR R'R'
OO
2R"2R"OOHH++
OOR"R"
RR R'R'CC
OOR"R"
+ H+ H22OO
mechanism:mechanism:
reverse of acetal formation;reverse of acetal formation;hemiacetal is intermediatehemiacetal is intermediate
application:application:
aldehydes and ketones can be aldehydes and ketones can be "protected" as acetals."protected" as acetals.
Hydrolysis of AcetalsHydrolysis of Acetals
Reduction Reactions
• Reducing Agents; LiAlH4 , NaBH4
ExamplesExamples
CH3CH2CCH2CH3
O+ LiAlH4
2) H 3O+
CH3CH2CHCH2CH3
OH
Reduction of Aldehydes and ketonesReduction of Aldehydes and ketones1. Hydrogenation1. Hydrogenation
2. Metal Hydrides2. Metal Hydrides
Wolff-Kishner reductionWolff-Kishner reduction
CCH3
O H+
NH2NH2CCH3
NNH2
KOHCH2CH3
Clemmensen reductionClemmensen reduction
CH2CH3CCH3
O
Zn/Hg
HCl
in aqueous solutionin aqueous solution
RCHRCH RCHRCH RCOHRCOH
OO OHOH
OHOH
HH22OOOO
Oxidation of AldehydesOxidation of Aldehydes
KK22CrCr22OO77
HH22SOSO44
HH22OO
OO
OO
CHCH
OO
OO
COHCOH
(75%)(75%)
viavia
OO
OHOH
CHCH
OHOH
ExampleExample