10-1
Alcohols & Thiols & Ethers SourcesStructure, Nomenclature, PropertiesAcidity and BasicityRx with active metalsConversion to R-X, inorganic acid halides
Rxs with HX SN1/SN2, sulfonatesDehydration of alcoholsOxidation of 1o and 2o alcoholsOxidation of glycols[Pinacol & Thiols/Sulfur chemistry - skip]
CH2
OH
6, 31, ss34
Chapter 10 Chapter 11
10-2
Chapter 10
H3C
CH3
H
H OH
CH
H3C F
HO
CH
H3CF
O
CO
H3C
H
OH
O
CO
H3C
OH
H
+
+
XH
H2 / M
Cl
IC
H
H3C D
NC
CH
H3CD
(-):CN:
CH2
OH O
HCH3
CH3
H
Br Mg CH3
δ+ δ−
LiCu
2
reactionsacid baseactive metal
substitution oxidation
sourcesnomenclature
(alcohol & ethers)properties
10-3
Preparation of alcohols - (review)
1. Hg(OAc)2/H2O 2. NaBH4
OR H+/H2O OH
OH1. BH3 2. H2O2/ -OH
RC
R
X
H
RC
R
OH
H
HO-
orH2O
R
C
R
CH2
1. OsO4/H2O OR2. KMnO4/-OH/cold
RC
R
C
OHOH
H H
RC
RO
RC
R
H
O
H2Met(cat.)e.g. Pt
H
10-4
Chapter 10
sourcesnomenclature
(alcohol & ethers)properties
reactionsacid baseactive metal
substitution oxidation
10-5
Nomenclature alcohols & ethersNomenclature alcohols & ethersIUPAC names – alcohol sp3C-OH
-longest chain that contains the -OH = root -OH gp lowest number- suffix -e to -ol
ether R-O-R’ sp3C, sp2C, spC in R & R’ bonded to O-always subsituent- #-prefix, alkoxy (special ethers #,#-epoxy)
1-ethoxy-2-butanol OHH
O H
10-6
Epoxides - 11 - special ethersNomenclature - #,#-epoxy (substituent) or oxirane
#,#-epoxy-#-pentyn-#-ol
(4S)-4,5-epoxy-2-pentyn-1-ol
ether acetylene alcoholO
H
OH
10-7
Nomenclature-AlcoholsNomenclature-AlcoholsIUPAC namesLongest chain that contains the -OH = rootGive -OH group lowest numberChange suffix -e to -ol
(S)-2-methyl-1-butanol
H3C
C CC OH
CH3
HH
H
H H
10-8
oxygen sp3
Structure - AlcoholsStructure - Alcohols
Alcohol functional group:
-OH group bonded to an sp3 hybridized carbon
bond angles ~ 109.5°
C O
HH
H3C
H
10-9
Physical PropertiesPhysical PropertiesHydrogen bonding: H bonded to an electronegative
atom (F, O, or N)
etc.
RO
H O
H
R
O
H
RO HR
Hydrogen bond weak (~ 5 kcal/mol)
10-10
Physical PropertiesPhysical Properties
ethanol & dimethyl ether - constitutional isomers but weak hydrogen bonds have dramatic effects:
bp -24°Cbp 78°C
CH3CH2 OH CH3OCH3
hydrogen bonds no hydrogen bonds
10-12Reactions
alcohols: acidbaseindirect substitutionindirect -eliminationactive metalsoxidation
ethers: baseindirect substitutionindirect -elimination
epoxides: substitution, indirect & direct
10-13
Acidity of AlcoholsAcidity of Alcohols
weak acids
conjugate bases strong
CH3O-H N H
CH3
+
H
H
CH3
NHCH3O -+
+
H
10-14
Compound pKa
-7
15.515.7
15.9
17
18
4.8
CH3 OHH2 O
CH3 CH2OH
(CH3 )2CHOH
(CH3 )3COH
CH3 CO2H
HClhydrogen chloride
acetic acid
methanolwaterethanol
2-propanol
2-methyl-2-propanol
Formula
Stronger acid
Weaker acid
Acidity of AlcoholsAcidity of Alcohols
RSH 8.5
10-15
Acidity of AlcoholsAcidity of AlcoholsAcidity on: stabilization and solvation
electron donation
destabilize alkoxides
decreases solvation
C O
H
R
RR
C O
R
RR
O
H
H
+
+ O
H
H
H
10-16
Alcohols + Li, Na, K (active metals)
form metal alkoxides
metal alkoxidesodium methoxide
alcohols rx alcohols rx withwith metals metals
2CH3OH + 2Na 2CH3O- Na+ H2+
10-17
+ NaH + H-HH
O H
H
O Na+
Na+ - H
rx with metalsrx with metals
HO
C + Ko + H2
H3C
H3C CH3
OC
H3C
H3C CH3
K+
sodium cyclohexoxide
10-18
basicity of alcohols/basicity of alcohols/ethersethers
weak Lewis base(water-like)
RO
C+H X
H3C
CH3H
R = H or alkyl
XR
OCH3C
CH3H
H +
oxonium ion
10-19
3° alcohols (ethers) react very rapidly with HCl, HBr, HI.
Alcohols/Alcohols/EthersEthers indirect indirect Substitution ( Substitution (with with HX)HX)
1°alcohols/ethers are unreactive under these conditions
CH3
O-R
CH3
Cl0oCether
+ +H-Cl HOR+
R = H or alkyl
10-20
2° alcohols + HBr (or HI )
racemization, rearrangement, olefins
HO H
+ HBr
ΔBr
Br H+
+
indirectindirect Substitution ( Substitution (with with HX)HX)
10-21
22oo or 3 or 3oo ROH/ ROH/ROR’ROR’ with HX - S with HX - SNN11
H
-H+
+X-+X-
H[-HOR]
good leaving group
racemization, rearrangement, olefins
O-RH
XXH+ +
ΔH-X + HOR
OH
H R
R = H or alkyl
10-22
11oo ROH/ ROH/ROR’ROR’ with with HI HI or or HBr - SHBr - SNN22
X(-) displace
R’ = H or alkyl
HO
R'
O
R'
H-
OR'
H
X+
OR'
XH X
Δ+ H-OR'
10-23
SO2 + HClC
O
CH3H
CCl
CH3H
S OCl
Cl
H
+ +weak
base
C
O
CH3H
H SO
Cl
Cl
O
H
SO
Cl
Et3N:
indirectindirect Substitution Substitution (with (with SOClSOCl22))
10-24
indirectindirect Substitution Substitution (with (with PBrPBr33))
O
H
CBr
H
P BrBr
Br
H
+ + PBr
BrHO
POH
BrHO 2nd ROH to RBr
POH
OHHO 3rd ROH to RBr
C
O
CH3H
H P
Br
Br
Br
10-25
indirectindirect Substitution Substitution
O
H
CBr
H
P BrBr
Br
H
+ + PBr
BrHO
SO2 + HClC
O
CH3H
CCl
CH3H
S OCl
Cl
H
+ +weak
base
CH3
O-R
CH3
Cl0oCether
+ +H-Cl HOR+
R= H, alkyl
OR'
XH X
Δ+ H-OR'
R’= H, alkyl; X= Br, I
10-26
sulfonic acid(a very strong acid)
H-O S RO
O
(a very weak base )
O S RO
O
alcohols - alcohols - alkyl sulfonatesalkyl sulfonates, good Lgp, good Lgp
10-27
alkyl sulfonates (sulfonate ester)alkyl sulfonates (sulfonate ester)
SS
S R
sulfonyl chloride
S R
O
O
Cl+C
O
CH2CH3
H3C
HH
CH
H3C
CH2CH3
O SO
ORpyridine + H-Cl
good leaving group for Sn2 rx
+C
OH3CH
CH2CH3N C:
SO
OR DMF +
C
HCH3
CH2CH3CN
O SO
OR
10-28
rx:
alkyl sulfonatesalkyl sulfonatesH
OH + Cl S
O
OCH3
NEt3 SO
O
CH3H
O+ H-Cl
SO
O
CH3H
O
OH
HH
H
prep:
O
H
+
OH
O
H
H
10-29
rx:
alkyl sulfonatesalkyl sulfonates
OH + Cl S
O
OR
NEt3S
O
O
R
O
NCSO
O
R
O
O
S
O
O R
C N + O S
O
OR
O
S
OO R
prep:
10-30
1° alcohols (ethers) with H2SO4 or H3PO4
dehydrationdehydration of of ROH/[-HOR’] ROH/[-HOR’] of of ROR’ROR’
180oCCH3CH2O-R
H2SO4CH2=CH2 + H-O-R
2° alcohols (ethers)
140oC
O-R+ H-O-RH2SO4
3° alcohols (ethers)
+ H-O-RCH3-C-O-R
CH3
CH3
50oC
H2SO4 CCH3
H3CCH2
R = H or alkyl
10-31
Dehydration Dehydration ofof RROH (-OR of ethers) OH (-OR of ethers)
Mechanism - same forward or reverse.
alkene addition and -elimination compete
RRC C C CR
R
R
R H O-R
R R[+ HOR]
[H+]
[- H-O-R]
[ H+ ]
10-33
Chapter 10
H3C
CH3
H
H OH
CH
H3C F
HO
CH
H3CF
O
CO
H3C
H
OH
O
CO
H3C
OH
H
+
+
XH
H2 / M
Cl
IC
H
H3C D
NC
CH
H3CD
(-):CN:
CH2
OH O
HCH3
CH3
H
Br Mg CH3
δ+ δ−
LiCu
2
sourcesnomenclature
properties
reactionsacid baseactive metal
substitution oxidation
10-34
OxidationOxidation
H2 O
Chromium(VI) oxide
CrO3+
Chromic acid
H2 O H2 CrO4H2 SO4
Potassiumdichromate
K2 Cr2O7 H2 SO4 H2 Cr2O7
10-35
Oxidation: 1° ROHOxidation: 1° ROHPyridinium chlorochromate (PCC):
pyridine + CrO3 [Cr(VI)] + HCl
N Cr
- ClO
O
OH
PCC converts 1° alcohols to aldehydes and 2o alcohols to ketones
N Cr H+ - Cl
O
O O
10-36
O
O
O
H HH
H
K2Cr2O7
OxidationOxidation
aldehydeO
H
O
H HH
PCC
O
Hacid
O
HH
PCCor H2CrO4or K2Cr2O7
Oketone
PCCor H2CrO4or K2Cr2O7
OH NR (no reaction)
10-37
R CR'
C
HH
H
X
B:
RC
R'C
HH :X-+
-elimination of H and chromate
R CR'
O
H
Cr
B:
O OH
O
RC
R'O :CrO3H+:CrO2
+ H-OH
+
10-38
Oxidation: 1° ROHOxidation: 1° ROH
hydrateC
O
HH
HC
O
O H
CO
HH
Cr
O
OOH
CO
H
C
O
H
O
H
H
C
O
H
O
Cr
O
O
OH
H
H2CrO4
- CrO2/ H2O
H+/H2CrO4
O HH
H2CrO4
- CrO2/ H2O
hydrate
10-39
Oxidation 1o and 2o ROH
K2Cr2O7
and many other reagents
OHHO
Br
CO2CH3
PCC OO
Br
CO2CH3H
OO
Br
CO2CH3HO
K2Cr2O7
10-40
Oxidation of Glycols with HOxidation of Glycols with H55IOIO66 (or HIO (or HIO44•2H•2H22O)O)
O
O
H
H
IOH
O
O
OH
+
O
OI O
O
OHH
+
acyclic or cis-1,2 cyclic diols
O
O
H
H
+ HIO4
O
O
+ HIO3HH
10-41
O
OI O
O
OHH
+
O
O
H
H
IOH
O
O
OH
Oxidation of Glycols with HOxidation of Glycols with H55IOIO66 (or HIO (or HIO44•2H•2H22O)O)
11
O
OI O
O
OHH
10-46
How does onemake butanalfrom 1-bromobutane?
Br
O
H
10-47
What else can be made using the chemistry of chapters 3, 6, 7, 8, 9, 10, 11 & “15”?
O
H
Br
OH
H H
PCC
Na(+) (-)OHDMF
10-48
Chapter 15
future chapter chemistry
CC
CC
O
H
H H
H H
CC
H
H
H
Br???
C
H H
HH
H
(CH3CH2CH2)2CuLi
CC
CC
H
H H
H
C
H H
HH
H
H1.) HB(SIA)2
2.) NaOH HOOH
H3CC
CC
OH
H
H H
H H
H
PCC
10-49
Chapter 10
H3C
CH3
H
H OH
CH
H3C F
HO
CH
H3CF
O
CO
H3C
H
OH
O
CO
H3C
OH
H
+
+
XH
H2 / M
Cl
IC
H
H3C D
NC
CH
H3CD
(-):CN:
CH2
OH O
HCH3
CH3
H
Br Mg CH3
δ+ δ−
LiCu
2
sourcesnomenclature
propertiesreactions
acid baseactive metalsubstitution oxidation
Chapter 11/15
H3C
CH3
H
H OH
CH
H3C F
HO
CH
H3CF
O
CO
H3C
H
OH
O
CO
H3C
OH
H
+
+
XH
H2 / M
Cl
IC
H
H3C D
NC
CH
H3CD
(-):CN:
CH2
OH O
HCH3
CH3
H
Br Mg CH3
δ+ δ−
LiCu
2
Recommended
