ald&ketoneii (origin)
TRANSCRIPT
Reactions of aldehydes and ketones:
oxidation
reduction
nucleophilic addition
1) Aldehydes are easily oxidized, ketones are not.
2) Aldehydes are more reactive in nucleophilic additions than ketones.
alkane alcohol
aldehydeketone
carboxylic acid
oxidation
reductionreduction
additionproduct
nucleophilicaddition
nucleophilic addition to carbonyl:
C
O+ Y Z C
Z
OY
Mechanism: nucleophilic addition to carbonyl
C
O+ Z
RDSC
O
Z
C
O
Z+ Y C
OY
Z
1)
2)
Mechanism: nucleophilic addition to carbonyl, acid catalyzed
C
O+ H C
OH
C
OH+ HZ
RDSC
OH
ZH
C
OH
ZH
C
OH
Z
+ H
1)
2)
3)
Aldehydes & ketones, reactions:
1) Oxidation
2) Reduction
3) Addition of cyanide
4) Addition of derivatives of ammonia
5) Addition of alcohols
6) Cannizzaro reaction
7) Addition of Grignard reagents
8) (Alpha-halogenation of ketones)
9) (Addition of carbanions)
1) Oxidation
a) Aldehydes (very easily oxidized!)
CH3CH2CH2CH=O + KMnO4, etc. CH3CH2CH2COOH
carboxylic acid
CH3CH2CH2CH=O + Ag+ CH3CH2CH2COO- + Ag
Tollen’s test for easily oxidized compounds like aldehydes.
(AgNO3, NH4OH(aq))
Silver mirror
Ketones only oxidize under vigorous conditions via the enol.
O
+ KMnO4 NR
O
Cyclohexanone
+ KMnO4, heat HOOCCH2CH2CH2CH2COOH
adipic acid
OH
enol
b) Methyl ketones:
RC
CH3
O+ OI-
RC
O-
O+ CHI3
iodoform
test for methyl ketonesYellow ppt
CH3CH2CH2CCH3 + (xs) NaOI CH3CH2CH2CO2- + CHI3
O
2-pentanone
2) Reduction:
a) To alcohols
H2, Ni
NaBH4 or LiAlH4
then H+
C
OC
OH
H
H2, Pt
1. NaBH4
2. H+
O
cyclopentanone
OHcyclopentanol
C CH3
OCHCH3
OH
acetophenone 1-phenylethanol
H
CO
H
H2, PtCH2OH
CH3CHCH=O
CH3 LiAlH4 H+
CH3CHCH2OH
CH3
benzaldehyde benzyl alcohol
isobutyraldehyde isobutyl alcohol
RDS1)
2)
mechanism: nucleophilic addition; nucleophile = hydride
hydride reduction
C
O+ H: C
H
O
C
H
O+ Al H C O Al
Al Al+
Then + H+ alcohol
Reduction
b) To hydrocarbons
NH2NH2, OH-
Zn(Hg), HCl
Clemmensen
Wolff-KishnerC
O
C
O
CH2
CH2
+ AlCl3
Zn(Hg), HCl
n-pentylbenzene
cannot be made by Friedel-Crafts alkylation due to rearrangement of carbocation
Cl
O O
3) Addition of cyanide
C
O 1. CN-
2. H+C
CN
OH
cyanohydrin
O + NaCN; then H+OH
CN
C
O
mechanism for addition of cyanidenucleophilic addition
RDSC
O
C
N
C
O
C
N
+ Na+ C
ONa
C
N
+ C N
then + H+
1)
2)
Cyanohydrins have two functional groups plus one additional carbon. Nitriles can be hydrolyzed to carboxylic acids in acid or base:
CH2CH
OHC N
H2O, OH-
heatCH2CH
OH
COO-
H2O, H+
heatCH
CH
COOHCH2CH
OHC N
4) Addition of derivatives of ammonia
O+
N+ H2OH2N G
(H+)
G
HN
phenylhydrazine
H2N NH2
hydrazine
H2N OH
hydroxylamine
HN NO2
O2N
2,4-dinitrophenylhydrazine
H2N NH
O
NH2
semicarbazide
H2NH2N
C
O+ H+
C
OH
C
OH+ H2N G
acid catalyzed nucleophilic addition mechanism followed by dehydration
C
NH2
OH
G
C
NH2
OH
G
C
NG
+ H2O + H+
RDS
1)
2)
3)
CH2 CHO
phenylacetaldehyde
+ H2NOH CH2 CH NOH
an oxime
O + H2NHNCNH2
O H+
NHNCNH2
O
a semicarbazonecyclohexanone
CH3CH2CH2CH2CHO + NHNH2
phenylhydrazine
hydroxylamine
semicarbazide
pentanal
CH3CH2CH2CH2CH N NH
a phenylhydrazone
melting points of derivativesketones bp semi- 2,4-dinitro- oxime
carbazone phenylhydrazone
2-nonanone 195 119 56
acetophenone 202 199 240 60
menthone 209 189 146 59
2-methylacetophenone 214 205 159 61
1-phenyl-2-propanone 216 200 156 70
propiophenone 220 174 191 54
3-methylacetophenone 220 198 207 55
isobutyrophenone 222 181 16394
5) Addition of alcohols
C
O+ ROH, H+
C
OR
OR acetal
C
OH
OR hemiacetal
Mechanism = nucleophilic addition, acid catalyzed
1) C
O+ H C
OH
2)C
OH2 + ROH C
OH
HOR
3) C
OH
HOR
C
OH
OR
+ H
RDS
CH2CHO(xs) EtOH, H+
CH2 CHOEt
OEt
O (xs) CH3OH, dry HClOCH3
OCH3
acetal
ketal
CHO
OHH
HHO
OHH
OHH
CH2OH
O
H
HO
H
HO
H
OHOHH H
OH
O
H
HO
H
HO
H
HOHH OH
OH
nucleophilic addition of -OH on carbon 5 to the aldehyde functional group
CHO
OHH
HHO
OHH
OHH
CH2OH
CH
OHH
HHO
OHH
HHOH2C
OH
O
H
HO
H
HO
H
OHOHH H
OH
O
O
H
HO
H
HO
H
HOHH OH
OH
rotate C-5 OH to rear
6) Cannizzaro reaction. (self oxidation/reduction)
a reaction of aldehydes without α-hydrogens
CHO
Br
conc. NaOH
CH2OH COO-
Br Br
+
CH3OH + HCOO-H2C=Oconc. NaOH
Formaldehyde is the most easily oxidized aldehyde. When mixed with another aldehyde that doesn’t have any alpha-hydrogens and conc. NaOH, all of the formaldehyde is oxidized and all of the other aldehyde is reduced.
Crossed Cannizzaro:
CH=O
OCH3
OH
vanillin
+ H2C=Oconc. NaOH
CH2OH
OCH3
OH
+ HCOO-
7) Addition of Grignard reagents.
C
O+ RMgX C
O
R
MgBr
C
O
R
MgBr+ H2O C
OH
R
+ Mg(OH)Br
larger alcohol
C
ORMgBr+
RDSC
O
R
+ MgBr
C
O
R
+ MgBr C
OMgBr
R
mechanism = nucleophilic addition
1)
2)
#3 synthesis of alcohols. Used to build larger molecules from smaller organic compounds.
RMgX +H
CH
ORCH2OMgX
H+RCH2OH
formaldehyde 1o alcohol + 1 C
RMgX +R'
CH
OR'CHOMgX
R
H+R'CHOH
Rother aldehydes 2o alcohol + X C's
R-MgX +R'
CR"
OR-COMgX
R'
R"
H+
R-COH
ketone3o alcohol + X C's
RMgX +H2C CH2
ORCH2CH2OMgX
H+
RCH2CH2OH
ethylene oxide 1o alcohol + 2 C's
R'
R"
Aldehydes & ketones, reactions:
1) Oxidation
2) Reduction
3) Addition of cyanide
4) Addition of derivatives of ammonia
5) Addition of alcohols
6) Cannizzaro reaction
7) Addition of Grignard reagents
8) (Alpha-halogenation of ketones)
9) (Addition of carbanions)
Planning a Grignard synthesis of an alcohol:
a) The alcohol carbon comes from the carbonyl compound.
b) The new carbon-carbon bond is to the alcohol carbon.
C
O+ RMgX H+
C
OH
R
New carbon-carbon bond
“The Grignard Song” (sung to the tune of “America the Beautiful”)
Harry Wasserman
The carbonyl is polarized,
the carbon end is plus.
A nucleophile will thus attack
the carbon nucleus.
The Grignard yields an alcohol
of types there are but three.
It makes a bond that corresponds
from “C” to shining “C.”
CH3CH2CH2CH2 C CH3
CH3
OH
2-Methyl-2-hexanol
CH3CH2CH2CH2MgBr + CH3CCH3
OH2O
CH3CH2CH2CH2 C CH3
CH3
OH
2-Methyl-2-hexanol
CH3CH2CH2CH2CCH3 + CH3MgBrH2O
O
or
ROH RX
-C=O
RMgX
R´OH
HX Mg
ox.
H2O larger alcohol
Stockroom:
alcohols of four-carbons or less:
(methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol.)
benzene
cyclohexanol
any needed inorganic reagents or solvents.
Grignard synthesis of 4-methyl-2-pentanol from alcohols of four-carbons or less:
Step one: determine the carbonyl compound and Grignard reagent that you would use:
CH3
CH3CHCH2CHCH3
OH
H2O CH3
CH3CHCH2MgBr + CH3CH=O
Step two: show the syntheses of the Grignard reagent and the carbonyl compound from alcohols…
CH3 HBr CH3 Mg CH3
CH3CHCH2OH CH3CHCH2Br CH3CHCH2MgBr
H+
K2Cr2O7 CH3
CH3CH2OH CH3CH=O CH3CHCH2CHCH3
special cond. OH
4-methyl-2-pentanol
Br2,FeBr
MgMgBr
CH3CHCH3
OH CrO3
CH3CCH3
O
H2OC CH3
CH3
OH
2-phenyl-2-propanol
2-phenyl-2-propanol
H3C OH
1-Methylcyclohexanol
OHH
Cyclohexanol
NaOCl
O
Cyclohexanone
CH3OHHBr
CH3BrMg
CH3MgBr
H2O
1-methylcyclohexanol
CH2OHH
Cyclohexylmethanol
OHH BrH MgBrH
CH3OH H2C=O
HBr Mg
K2Cr2O7
special cond.
H2O
cyclohexylmethanol
aldehyde RCOOHketone
ROR
alkyne
alkene
RH
RX
ROH
Alcohols are central to organic syntheses
ROH RX
-C=O
RMgX
R´OH
HX Mg
ox.
H2O larger alcohol
Using the Grignard synthesis of alcohols we can make any alcohol that we need from a few simple alcohols. From those alcohols we can synthesize alkanes, alkenes, alkynes, alkyl halides, ethers, aldehydes, ketones, carboxylic acids…
eg. Outline all steps in a possible laboratory synthesis of 3-methyl-1-butene from alcohols of four carbons or less.
CH3
CH3CHCH=CH2
Retrosynthesis:
alkenes, syntheses:
1. Dehydrohalogenation of an alkyl halide
2. Dehydration of an alcohol
3. Dehalogenation of a vicinal dihalide
4. Reduction of an alkyne
Methods 3 & 4 start with compounds that are in turn made from alkenes.
Dehydration of an alcohol?
CH3 H+
CH3CHCHCH3 yields a mixture of alkenes OH
CH3 H+
CH3CHCH2CH2-OH yields a mixture of alkenes
E1 mechanism via carbocation!
Dehydrohalogenation of an alkyl halide?
CH3 KOH(alc)CH3CHCHCH3 yields a mixture of alkenes Br
CH3 KOH(alc) CH3
CH3CHCH2CH2-Br CH3CHCH=CH2
only product E2 mechanism, no carbocation, no rearrangement
CH3 HBr CH3
CH3CHCH2CH2-OH CH3CHCH2CH2-Br
1o alcohol, SN2 mechanism, no rearrangement!
CH3 KOH(alc) CH3
CH3CHCH2CH2-Br CH3CHCH=CH2
Use the Grignard synthesis to synthesize the intermediate alcohol from the starting materials.
CH3 PBr3 CH3 Mg CH3 CH3CHCH2-OH CH3CHCH2Br CH3CHCH2MgBr
K2Cr2O7
CH3OH H2C=O special cond. H2O
CH3
CH3CHCH2CH2-OH
HBr
CH3 KOH(alco) CH3
CH3CHCH=CH2 CH3CHCH2CH2-Br