O
Chapter19
Aldehydesandketones
O
R
(S)-carvone
O
H
R
R'
O
(R)-carvone
H
O
redrawn:
CHO
CHO
citronellal
R
19.1
S
Nomenclature:asbefore,butuse“al”asthesuffixforaldehydes,and
“one”forketones
1.
2.
3.
4.
H
O
Findlongestchaincontainingthecarbonyltoserveasbasename
(priority:aldehydes>ketones>alcohols>alkenes≈alkynes>halides>alkanes)
Namesubstituents(groupsnotinlongestchain,table4.2)
Assignnumberstosubstituentstoshowpositiononlongestchain
Putitalltogether,alphabetically!
same
as:
CHO
CHO
(aldehyderightnexttoaring)
Commonnames
forafewmolecules
thatyoushouldknow:
O
H
H
O
formaldehyde
O
H
O
acetaldehyde
O
acetone
19.2
Preparationofaldehydesandketones:reactionsyoualreadyknow(fromsection12.10)!
generalreactions:examples:
OH
OH
R
R'
2o alcohol:
R & R' = C
Na2Cr2O7,
H2SO4, H2O
or
R
R'
CrO3,
H2SO4, H2O
CrO3, H2SO4, H2O
OH
PCC
R
H
O
PCC
R
O
96%
O
or
OH
Na2Cr2O7,
H2SO4, H2O
OH
H
O
88%
PCC
93%
O
H
1o
alcohol:
R=C
(Theotherreactionsgiveninsection19.3areonesthatwehaven’tcovered,soyoucanignorethem….fornow!)
19.3
Reactivityofcarbonyls:governedbyelectronicsandsterics
mostreactiveleastreactive
19.4
Hydrationofcarbonyls:aldehydesvs.ketones
O
HO OH
O
HO OH
+ H2O
+ H2O
H
H
Nucleophilicadditionunderbasicconditions(strongNu:),forexample,thehydrationofacarbonylwithNaOH,H2O
NaOH
O
HO OH
+ H2O
H
H
Nucleophilicadditionunderacidicconditions(protonationneededforweakNu:),forexample,hydrationwithH3O+,H2O
H3O+
O
+
H
19.5
H2O
HO OH
H
Reactionsofketonesandaldehydeswithnucleophilesthatyoualreadyknow:
generalreactions:examples:
_
HydridesH:
O
NaBH4, R"OH
R R'
or:
1. LiAlH4
2. H3O+
Grignardreagents
R
OH
R
R'
1. LiAlH4,
2. H3O+
O
1.
O
MgBr
2. H3
O+
OH
H
93%
R
R'
O
MgBr
2. H3O+
54%
19.6
HH
OH
1.
Thesereactionsaremorelike:
a)  acid-catalyzedNuattack
b)  base-catalyzedNuattack
OH
90%
1. R"MgX
2. H3O+
R'
OH
85%
H
H
O
NaBH4, EtOH
O
OH
Newreactionsofaldehydesandketones—oxygennucleophiles:hydration(previousslide)
acetalformation(here)
Examples:
aldehydesketones
O
O
H3CO OCH3
CH3OH, H+
EtOH, H+
H
H
CH3
97%
89%
+ H2O
OEt
CHO
O
HO
O
O
OEt
OH
EtOH, HCl
O
OEt
AcO + H2O
AcO
O
O
HO
+
H
OH
Br H C
O
O
CH3
3
HO
+ H2O
H
H3C
73%
H
H3C
OH
75%
Generalreaction:
19.7Mechanism(afterthenextslide)
EtO
OEt
CH3
+ H2O
H+
O
O
O
OEt
+ H2O
H+
Br
O
H3C
O
CH3
+ H2O
Newreactionsofaldehydesandketones—oxygennucleophiles:acetalformation
Generalreaction:
R"O OR"
R"OH, H+
+ H2O
R
R'
O
HO R" OH
R
R'
R"
HO
O
H+
+
OH H
for example:
O
O
R, R' = C or H
O O
H
H3C
73%
H
H3C
R
R'
+ H2O
Supposeyouwantedtomakethecompoundintheboxbelow.Whichaldehyde/ketonewouldyouuse?
a.
d. OH
O
OMe
O
OMe
b.
e
H
H
CHO
c.
O f.
MeOH
19.8
Newreactionsofaldehydesandketones—oxygennucleophiles:acetalformation
Generalreaction:
R"O OR"
R"OH, H+
+ H2O
R
R'
O
HO R" OH
R
R'
R"
O
H+
for example:
R, R' = C or H
O O
H
H3C
R
R'
Nowwhichalcoholwouldyouuse?
OMe
OMe
a.
OH b.
O
H
H
d.
e.
CH3CH2OH
19.9
HO
OH
H+
73%
O
O
H3C
H
+ H2O
c.
f.
OH
CH3OH
OH
Newreactionsofaldehydesandketones—oxygennucleophiles:acetalformation
Generalreaction:
O
R
R'
R, R' = C or H
Mechanism:
19.10
R"OH, H+
R"O
OR"
R
HO R" OH
H+
R'
+ H2O
R"
O
O
R
R'
for example:
H3C
HO
O
H
OH
73%
H+
O
O
H3C
H
+ H2O
Newreactionsofaldehydesandketones—nitrogennucleophiles:
Imineformation(usesaprimaryamine):
O
NH2
H+
+
N
95%
+ H2O
Enamineformation(usesasecondaryamine):
H
H+
O
N
+
N
+ H2O
90%
Whatabouttertiaryamines?
19.11
Newreactionsofaldehydesandketones—nitrogennucleophiles:Imineformation
Examples:
aldehydesketones
O
NH2
NH2
H+
O
+
H+
N
95%
H +
H
+ H2O
O
NH2
O
NH2
+
H+
H
N
+
H
82%
78%
H
HO
HO
H
Generalreaction:
Mechanism(nextslide)
19.12
N
+ H2O
N
H
+ H2O
Newreactionsofaldehydesandketones—nitrogennucleophiles:Imineformation
Generalreaction:
Mechanism:
19.13
O
R
+
R'
R" NH2
H+
N
R
R"
R'
+ H2O
Newreactionsofaldehydesandketones—nitrogennucleophiles:Enamineformation
Examples:
aldehydesketones
H
H+
N
O
N
+
60%
H
+ H2O
H
H
O
N
+
CH3
N
H
CH3
H+
N
+
70%
O
H
H
+ H2O
O
+
(CH3)2NH
Generalreaction:
Mechanism(nextslide)
19.14
H+
90%
H+
57%
N
+ H2O
N(CH3)2
+ H2O
Newreactionsofaldehydesandketones—nitrogennucleophiles:Enamineformation
O
Generalreaction:
+
R"
R
R'
H
there must be an H
on this carbon
Mechanism:
So,whatabouttertiaryamines?
19.15
NH
R*
H+
R*
R
N
R"
R'
+ H2O
Newreactions—hydrolysisofacetals,imines,andenamines
Theformationofacetals,imines,andenaminesareactuallyreversibleprocesses(thatis,theyare
trueequilibriumreactions),sowecanuseconditionstofavoreitherthereactantsortheproducts.
Acetals:
O
H+
R"O OR"
+
+
R"OH,
H
+ H2O
R
R'
R
R'
R" = C
R, R' = C or H
Imines:
O
R"
H+
N
+
R" NH2
R
R'
+ H2O
R
R'
R" = C
R, R' = C or H
Enamines:
O
R*
R"
H+
+
N
R" NH
R
R'
R
+ H2O
R*
R'
H
R", R* = C
R, R' = C or H
Thebookcoversthehydrolysisofacetalsverywell,sowewilldothehydrolysisofimines.Youshould
workoutthemechanismforthehydrolysisofenamines.
19.16
Newreactions—hydrolysisofimines
Generalreaction:
Mechanism:
19.17
O
R
+
R'
R, R' = C or H
R" NH2
H+
N
R
R" = C
R"
R'
+ H2O
Newreactionsofaldehydesandketones—nitrogennucleophiles:Wolff-Kischnerreduction
Examples:
H
H
1. H2NNH2, H+
2. KOH, H2O, heat
H
52%
O
Generalreaction:
Mechanism(imineformationandthen…..)
19.18
O
1. H2NNH2, H+
2. KOH, H2O, heat
H
69%
O
Chapter20
Carboxylicacids
andderivatives
Sections20.1through20.12
Wewon’tcovernomenclatureinclass,butyouarestillresponsibleforknowingit.
SpecificthingsinthesesectionsforwhichyouareNOTresponsible:
Nomenclatureofdiacids
CarboxylicacidsatPhysiologicalpH
20.1
Generalformulaforcarboxylicacidderivatives:
O
Z = a heteroatom (an atom that is not = H or C)
R
Z
Specificderivativesandrelativereactivity:
O
O
most reactive
R
X
R
O
O
O
R'
20.2
OR'
OH
X=Br, Cl
acid
halides
R
O
acid
anhydrides
esters (OR')
acids (OH)
R
NH2
NHR'
NR'2
amides
least reactive
Apreparationofcarboxylicacidsthatyoualreadyknow(oxidationof1oalcohols):
generalreaction:
Na2Cr2O7,
O
H2SO4, H2O
R
OH
R
OH
or
CrO3,
H2SO4, H2O
examples:
Na2Cr2O7,
H2SO4, H2O
OH
O
OH
49%
CrO3,
H2SO4, H2O
O
OCH3
OH
67%
O
Skip“OxidativecleavageofAlkynes”and“OxidationofAlkylbenzenes”
20.3
OCH3
Preparationsofcarboxylicacids--Newreactions:Nitrilehydrolysis
CarboxylationofGrignards
Examples:
C
N
OH
C
N
O
C
HO
Generalreaction:
20.4
N
C
O
H+, H2O, heat
HO
OH
97%
O
OH
H+, H2O, heat
OH
52%
N
O
O
H+, H2O, heat
65%
HO
O
OH
We’renotgoingtoworryaboutthemechanismofthisone(butIbetyoucanfigureitout).
Preparationsofcarboxylicacids--Newreactions:Nitrilehydrolysis
CarboxylationofGrignards
Examples:
1. Mg
2. CO2
Cl
3. H+, H2O
86%
Generalreaction:
Mechanism
20.5
Br
O
OH
1. Mg
2. CO2
3. H+, H2O
86%
CO2H
Interconvertingcarboxylicacidderivatives:generalmechanisms
O
O
O
O
O
most reactive
R
OR'
R
R'
O
R
X
R
NH
OH
X=Br, Cl
NHR'
NR'
acid
esters (OR')
acid
amides
halides
acids (OH)
anhydrides
2
2
MechanismA(foracid,becausewestartwithH+transfer)
MechanismB(forbase/Nu,becausewestartwithNuattack)
MechanismBH(foraneutralbase/NuwithanHattached)
20.6
least reactive
acidhalides:preparationandreactions
2 equivalents NH3, R*NH2, R*2NH
to give carboxylic acid: H2O (-HCl)
to give ester: R"OH, pyridine (-pyr-HCl)
O
O
R'
O
O
most reactive
R
R
X
O
O
O
R'
R
O
OR"
R
OH
X=Br, Cl
NHR*
NR*2
from carboxylic acid only:
SOCl2 (- SO2, -HCl)
or SOBr2
1. LAH (excess)
2. H2O
1. LiAl(O-tBu)3H
2. H2O
1. excess R'MgBr
2. H2O
OH
R
20.6
H
H
O
R
OH
H
R
R'
NH2
R'
least
reactive
acidanhydrides:preparationandreactions
NH3 or R*NH2 or R*2NH
O
O
R"OH (to give ester)
or H2O (to give
carboxylic acid)
R'
O
O
most reactive
R
X
R
O
O
O
R'
R
X=Br, Cl
20.7
Reactionsinbluehaveappearedonanearlierslideinthissection.
O
OR"
OH
R
NH2
NHR*
NR*2
least
reactive
esters:preparationsandreactions
OH
O
R
1. excess LAH
2. H2O
ester: R'OH, pyridine (-pyr-HCl)
R"OH
O
O
X
R
O
R
R'
R'
OR"
NH3 (slow)
O
H2O,
H2SO4
R
X=Br, Cl
H2O
1. NaOH
2. H3O
O
R
OH
1. LAH
2. H3O+
H H
R
20.8
OH
1. excess R'MgBr
2. H2O
R"OH,
H2SO4
R'
H
1. DIBAH
2. H2O
1. NaOH
2. CH3I
most reactive
R
R
O
R
O
H
H
OH
NH2
least
reactive
amides:preparationsandreactions
2 equivalents NH3, R*NH2, R*2NH
NH3 or R*NH2 or R*2NH
NH3 (slow)
O
O
O
most reactive
R
X
R
O
O
R
O
OR"
R'
R
X=Br, Cl
OH
least reactive
NHR'
NR'2
O
R
NH2
H3O+ or
1. NaOH, heat
2. H3O+
1. LAH (excess)
2. H2O
SOCl2, base
R
20.9
C N
H
H
R
NH2
Chapter21
Alittlebitofα-carbonchemistry
Sections21.1,21.4,and21.6only
21.1
Chapters20&21wereallaboutnucleophilicadditiontoC=Ocarbonin
carbonylcompounds:
overall reaction:
OH
O δ−
Nu: & H+
+
Nu
δ
R
R'
R'
R
Inthischapter,wewillfocusonusingtheα-carbonasanucleophile:
O
O
O
δ
δ
δ
β
δ
β
β
β
H
O
α
α
α
α
γ
γ
γ
γ
Andα,β-unsaturatedcarbonylsaselectrophiles:
O
γ
21.2
O
β
δ
α
β
α
δ
γ
O
β
δ
γ
α
β
δ
H
γ
α
O
Keto-enoltautomerization—explainshowαcarbonscanfunctionasnucleophiles
Inacetone,forexample,theequilibriumliesfaronthe“keto”side(theleftside)
K=
Acid-catalyzedtautomerization:
Base-catalyzedtautomerization(weakbase):
21.3
Quantitativeformationofanenolate(usesastrongbase):
Enolsandenolatesactingasnucleophiles,attackingR—X(anelectrophile):
Enolate:
Enol:
21.4
TheClaisenCondensation:
Examples:
1. NaOEt, EtOH
O
2. H3O+
OEt
75%
Generalreaction:
Mechanism:
21.5
O
O
OMe
OEt
MeO
1. NaH
2. H3O+
O
OMe
O
OMe
O
MeO
OMe
96%
MeO
OMe
α,β-unsaturatedcarbonylsaselectrophiles(conjugateadditions=Michaelreactions):
Examples:
O
O
EtO
OEt
Generalreaction:
Table22.2
21.6
1. NaOEt, EtOH
O
2.
O
EtO
1. NaOH or KOH
O
2.
O
OEt
3. H3O+
71%
O
O
O
O
3. H3O+
92%
O
O
α,β-unsaturatedcarbonylsaselectrophiles(conjugateadditions=Michaelreactions):
Generalreaction:
Mechanism:
21.7
1. NaOH or KOH
2.
O
R
O
Y
3. H3O+
O
Z
Y, Z = C, H, O
O
R'
92%
R, R' = C, H, O
O
Y
Z
R
R'
O