Download - Ald&KetoneII
![Page 1: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/1.jpg)
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.
![Page 2: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/2.jpg)
alkane alcohol
aldehydeketone
carboxylic acid
oxidation
reductionreduction
additionproduct
nucleophilicaddition
![Page 3: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/3.jpg)
nucleophilic addition to carbonyl:
C
O+ Y Z C
Z
OY
![Page 4: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/4.jpg)
Mechanism: nucleophilic addition to carbonyl
C
O+ Z
RDSC
O
Z
C
O
Z+ Y C
OY
Z
1)
2)
![Page 5: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/5.jpg)
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)
![Page 6: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/6.jpg)
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)
![Page 7: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/7.jpg)
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
![Page 8: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/8.jpg)
Ketones only oxidize under vigorous conditions via the enol.
O
+ KMnO4 NR
O
Cyclohexanone
+ KMnO4, heat HOOCCH2CH2CH2CH2COOH
adipic acid
OH
enol
![Page 9: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/9.jpg)
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
![Page 10: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/10.jpg)
2) Reduction:
a) To alcohols
H2, Ni
NaBH4 or LiAlH4
then H+
C
OC
OH
H
![Page 11: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/11.jpg)
H2, Pt
1. NaBH4
2. H+
O
cyclopentanone
OHcyclopentanol
C CH3
OCHCH3
OH
acetophenone 1-phenylethanol
H
![Page 12: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/12.jpg)
CO
H
H2, PtCH2OH
CH3CHCH=O
CH3 LiAlH4 H+
CH3CHCH2OH
CH3
benzaldehyde benzyl alcohol
isobutyraldehyde isobutyl alcohol
![Page 13: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/13.jpg)
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
![Page 14: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/14.jpg)
Reduction
b) To hydrocarbons
NH2NH2, OH-
Zn(Hg), HCl
Clemmensen
Wolff-KishnerC
O
C
O
CH2
CH2
![Page 15: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/15.jpg)
+ AlCl3
Zn(Hg), HCl
n-pentylbenzene
cannot be made by Friedel-Crafts alkylation due to rearrangement of carbocation
Cl
O O
![Page 16: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/16.jpg)
3) Addition of cyanide
C
O 1. CN-
2. H+C
CN
OH
cyanohydrin
O + NaCN; then H+OH
CN
![Page 17: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/17.jpg)
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)
![Page 18: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/18.jpg)
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
![Page 19: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/19.jpg)
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
![Page 20: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/20.jpg)
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)
![Page 21: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/21.jpg)
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
![Page 22: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/22.jpg)
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
![Page 23: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/23.jpg)
5) Addition of alcohols
C
O+ ROH, H+
C
OR
OR acetal
C
OH
OR hemiacetal
![Page 24: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/24.jpg)
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
![Page 25: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/25.jpg)
CH2CHO(xs) EtOH, H+
CH2 CHOEt
OEt
O (xs) CH3OH, dry HClOCH3
OCH3
acetal
ketal
![Page 26: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/26.jpg)
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
![Page 27: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/27.jpg)
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
![Page 28: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/28.jpg)
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-
![Page 29: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/29.jpg)
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
![Page 30: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/30.jpg)
C
ORMgBr+
RDSC
O
R
+ MgBr
C
O
R
+ MgBr C
OMgBr
R
mechanism = nucleophilic addition
1)
2)
![Page 31: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/31.jpg)
#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
![Page 32: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/32.jpg)
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"
![Page 33: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/33.jpg)
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)
![Page 34: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/34.jpg)
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
![Page 35: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/35.jpg)
“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.”
![Page 36: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/36.jpg)
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
![Page 37: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/37.jpg)
ROH RX
-C=O
RMgX
R´OH
HX Mg
ox.
H2O larger alcohol
![Page 38: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/38.jpg)
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.
![Page 39: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/39.jpg)
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…
![Page 40: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/40.jpg)
CH3 HBr CH3 Mg CH3
CH3CHCH2OH CH3CHCH2Br CH3CHCH2MgBr
H+
K2Cr2O7 CH3
CH3CH2OH CH3CH=O CH3CHCH2CHCH3
special cond. OH
4-methyl-2-pentanol
![Page 41: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/41.jpg)
Br2,FeBr
MgMgBr
CH3CHCH3
OH CrO3
CH3CCH3
O
H2OC CH3
CH3
OH
2-phenyl-2-propanol
2-phenyl-2-propanol
![Page 42: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/42.jpg)
H3C OH
1-Methylcyclohexanol
OHH
Cyclohexanol
NaOCl
O
Cyclohexanone
CH3OHHBr
CH3BrMg
CH3MgBr
H2O
1-methylcyclohexanol
![Page 43: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/43.jpg)
CH2OHH
Cyclohexylmethanol
OHH BrH MgBrH
CH3OH H2C=O
HBr Mg
K2Cr2O7
special cond.
H2O
cyclohexylmethanol
![Page 44: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/44.jpg)
aldehyde RCOOHketone
ROR
alkyne
alkene
RH
RX
ROH
Alcohols are central to organic syntheses
![Page 45: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/45.jpg)
ROH RX
-C=O
RMgX
R´OH
HX Mg
ox.
H2O larger alcohol
![Page 46: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/46.jpg)
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
![Page 47: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/47.jpg)
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.
![Page 48: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/48.jpg)
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!
![Page 49: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/49.jpg)
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
![Page 50: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/50.jpg)
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.
![Page 51: Ald&KetoneII](https://reader033.vdocument.in/reader033/viewer/2022042820/55cf9a9f550346d033a2a08c/html5/thumbnails/51.jpg)
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