Alcools

Report
Alcohols, phenols, and ethers
© E.V. Blackburn, 2012
Structure
R-OH alcohol
R = alkyl group (substituted or unsubstituted)
H
R C OH
H
R'
R C OH
H
1o
2o
R'
R C OH
R"
3o
© E.V. Blackburn, 2012
Nomenclature of alcohols
Add the suffix ol to the name of longest, linear, carbon
chain which includes the carbon bearing the OH and
any double or triple C-C bond.
The OH group has a higher priority than a multiple CC bond, a halogen, and an alkyl group in determining
the carbon chain numbering.
5-phenyl-2-hexanol
OH
© E.V. Blackburn, 2012
Nomenclature of alcohols
CH2CH2OH
CH3CH=CHCH2CH2OH
3-penten-1-ol
2-phenylethanol
F
OH
trans-3-fluorocyclohexanol
© E.V. Blackburn, 2012
Nomenclature of alcohols
OH
O
H3C C C
H OH
2-hydroxypropanoic acid
© E.V. Blackburn, 2012
Nomenclature of alcohols
CH2CH2CH3
H3CH2C
OH
H
3-hexanol?
© E.V. Blackburn, 2012
Cahn - Prelog - Ingold rules
Step 1: assign a priority to the 4 atoms or groups of
atoms bonded to the stereogenic carbon:
1. If the 4 atoms are all different, priority is determined by
atomic number. The atom of higher atomic number has the
higher priority.
H
HO
NH 2
CH3
© E.V. Blackburn, 2012
Determination of priority
2. If priority cannot be determined by (1), it is determined
by a similar comparison of atoms working out from the
stereogenic carbon.
4
H H H H
H C C
C H
H H Cl H
1
In the methyl group, the second atoms are H, H, H
whereas in the ethyl group, they are C, H, H.
The priority sequence is therefore Cl, C2H5, CH3, H.
© E.V. Blackburn, 2012
Cahn - Prelog - Ingold rules
3. A double or triple bond to an atom, A, is considered
as equivalent to two or three single bonds to A:
H
C O
H
OH
CH2OH
H
O
O
The sequence is therefore -OH, -CHO, -CH2OH, -H.
© E.V. Blackburn, 2012
Step 2
Arrange the molecule so that the group of lowest priority
is pointing away from you and observe the arrangement
of the remaining groups:
CH2CH3
CH2CH3
R
CH3
Cl
H
Cl
H3C
H
If, on going from the group of highest priority to that of second
priority and then to the group of third priority, we go in a
clockwise direction, the enantiomer is designated (R).
© E.V. Blackburn, 2012
Step 2
CH2CH3
CH2CH3
(S)
CH3
Cl
H
Cl
H3C
H
If the direction is counterclockwise, the enantiomer is
designated (S).
Thus the complete name for one of the enantiomers of 2chlorobutane is (S)-2-chlorobutane which is, by chance,
the dextrorotatory enantiomer. There is no correlation
between (+)/(-) and (R)/(S).
© E.V. Blackburn, 2012
R or S?
Br
H
HO
NH 2
CH3
H
C O
H
OH
CH2OH
H3C
H
CH2CH3
OH
H3CH2C
CH3
H
CH3
H
© E.V. Blackburn, 2012
Nomenclature of alcohols
Br
Cl
OH
CH3
3-bromo-3-chloro-2-methyl-2-propen-1-ol?
© E.V. Blackburn, 2012
E-Z designations
Br
Cl
OH
(Z)- 3-bromo-3-chloro-2-methyl-2-propen-1-ol
CH3
• use the Cahn-Ingold-Prelog system to assign priorities to
the two groups on each carbon of the double bond.
• then compare the relative positions of the groups of
higher priority on these two carbons.
• if the two groups are on the same side, the compound
has the Z configuration (zusammen, German, together).
• if the two groups are on opposite sides, the compound
has the E configuration (entgegen, German, across).
© E.V. Blackburn, 2012
E-Z designations
OH
H
CH
H 3
© E.V. Blackburn, 2012
Sterols - the steroid ring
system
12
3
11
D 16
1
C
9
14
A
B
7
5
HO
cholesterol
© E.V. Blackburn, 2012
Physical properties of alcohols
Alcohols are noticeably less volatile; their melting points are
greater and they are more water soluble than the
corresponding hydrocarbons having similar molecular
weights.
These differences are due to the OH group which renders a
certain polarity to the molecule. The result is an important
intermolecular attraction:
- + - + O H O H O H
R
R
R
the hydrogen bond
~ 21 - 25 kJ/mol
© E.V. Blackburn, 2012
Solubility of alcohols
Low molecular weight alcohols are water soluble:
- + - + - +
O H O H O H
R
H
R
© E.V. Blackburn, 2012
Spectroscopic properties
IR:
Associated alcohols (hydrogen bonded) show a broad
absorption in the 3300 - 3400 cm-1 range.
1H
NMR:
Absorption occurs in the range  = 3.5 to 4.5. Coupling is
not observed due to rapid H - H exchange.
© E.V. Blackburn, 2012
Fermentation
Fermentation of sugar by yeast gives C2H5OH.
Methanol is added to denature it.
© E.V. Blackburn, 2012
Azeotropic mixtures
The bp of ethanol is 78.3C whereas that of water is
100C (at least on Vancouver’s waterfront!). Can we
separate a mixture by distillation?
No! An azeotropic mixture forms!
An azeotropic mixture is one whose liquid and vapor
forms have identical compositions. The mixture
cannot be separated by distillation.
eg C2H5OH (95%) and H2O (5%) - bp 78.13C
H2O (7.5%), C2H5OH (18.5%) and C6H6 (74%) - bp
64.9C
© E.V. Blackburn, 2012
Oxymercuration
© E.V. Blackburn, 2012
Oxymercuration
An anti addition via a mercurinium ion:
CH3CO2-
Dissociation: Hg(OAc) 2
+
+ HgOCOCH 3
+
HgOCOCH 3
Electrophilic
attack:
CH3
+
HgOCOCH 3
+
HgOCOCH 3
Nucleophilic
opening:
CH3
H-O-H
CH3
CH3
OH
Hg OCOCH 3
H
© E.V. Blackburn, 2012
Oxymercuration
Why do we observe Markovnikov addition?
+
HgOAc


HgOAc
In the mercurinium ion, the positive charge is shared
between the more substituted carbon and the mercury
atom.
Only a small portion of the charge resides on this carbon
but it is sufficient to account for the orientation of the
addition but is insufficient to allow a rearrangement to
occur.
© E.V. Blackburn, 2012
Hydroboration
H.C. Brown and G. Zweifel, J. Am. Chem. Soc., 83, 2544 (1961)
H2O2
+ (BH3)2
diborane
H B
OH
-
+ B(OH) 3
H OH
© E.V. Blackburn, 2012
Hydroboration
1. (BH3)2
H3C
2. H2O2/OH-
3HC
H
syn
addition
H OH
trans-2-methylcyclopentanol
(CH3)3CCH=CH2
(CH3)3CCH2CH2OH
no rearrangement
no carbocation!
© E.V. Blackburn, 2012
Hydroboration - the
mechanism
CH3CH=CH 2
CH3CH=CH2
HX
1. (BH3)2
-
2. H2O2/OH

CH3CH
CH3CH2CH2OH
CH2
+
CH3CHCH3 + X-
H
X 
© E.V. Blackburn, 2012
Hydroboration - the mechanism
CH3CH=CH 2
1. (BH3)2
-
2. H2O2/OH

CH3 > CH

CH3 > CH
H
CH3CH2CH2OH
CH2

H B H
H
CH2

B H
H
© E.V. Blackburn, 2012
Hydroboration - the mechanism
R
R B
O-OH
R
R
R -B O OH
R
RO
B OR
RO
R
R -B O OH
R
R
+
HO
B OR
R
HO -
3ROH + BO 33-
© E.V. Blackburn, 2012
Reduction of carbonyls
© E.V. Blackburn, 2012
Reduction of carbonyls
© E.V. Blackburn, 2012
Reduction of carbonyls
H 3B H
O
H
-
O
H 2O
H
O-
H
OH
hydride transfer
© E.V. Blackburn, 2012
Reduction of acids
1. LiAlH 4, THF
RCH2OH
RCO2H
+
2. H3O
1o alcohol
© E.V. Blackburn, 2012
Reduction of esters
i. LiAlH 4
O
R
+
OR' ii. H
O
CH3CH2CH=CHCOCH 2CH3
RCH2OH + R'OH
1. LiAlH 4
2. H+
CH3CH2CH=CHCH 2OH + CH3CH2OH
© E.V. Blackburn, 2012
Reactivity of the carbonyl
group


R
o
120

C
'R
sp2

O

© E.V. Blackburn, 2012
Nucleophilic addition

Nu 
R
O
R'
:Nu
R
O
'R
+
Nu
R
O
R'
-
H 2O
+
Nu
R
O
R'
+
Nu
R
OH
R'
© E.V. Blackburn, 2012
Preparation of alcohols Grignard synthesis
dry
RMgX
RX + Mg
ether
R MgX
R
O
-
 
O
+
MgX
H2O
R
R
O
-
+
MgX
OH + Mg(OH)X
© E.V. Blackburn, 2012
The Grignard reagent
© E.V. Blackburn, 2012
Grignard synthesis
H
RMgX H
C O
H C OMgX
H
R
H3O+
'
R
RMgX R
C O
H C OMgX
H
R
aldehyde
OH
primary alcohol
formaldehyde
'
H
H
R
H3O+
'R
H
R
OH
secondary alcohol
© E.V. Blackburn, 2012
Grignard synthesis
'
'
R
RMgX R
''
C O
R C OMgX
''
R
R
H3O+
ketone
H O H RMgX
H
H
ethylene oxide
RCH2CH2OMgX
'R
"R
OH
R
tertiary alcohol
H3O+
RCH2CH2OH
primary alcohol
© E.V. Blackburn, 2012
Planning a Grignard synthesis
CH3
H3CH2CH2CH2C C OH
© E.V. Blackburn, 2012
Limitations
• Any hydrogen bonded to an electronegative element
(including an acetylenic hydrogen) is sufficiently acidic
to react with a Grignard reagent.
CH3MgI + H2O
R-CC-H + R':MgX
CH4 + Mg(OH)I
R-CC-MgX + R':H
• Grignard reagents react with O2, CO2 and with
almost all organic compounds which contain multiply
bonded C-O or C-N units.
© E.V. Blackburn, 2012
Reactions of alcohols
The reactions of alcohols involve one of two processes:
• breaking of the O-H bond
• breaking of the C-O bond
© E.V. Blackburn, 2012
Reactions involving O-H bond
breaking
RO- + M+ + 1/2 H2
R-OH + M
CH3CH2OH
Na
CH3CH2O- Na +
sodium ethoxide
© E.V. Blackburn, 2012
Phenols
OHArOH
water
insoluble
H+
ArOphenoxide ion
soluble
Ka ~ 10-10
© E.V. Blackburn, 2012
Acidity of phenols
ArOH + H2O
ArO - + H3O+
© E.V. Blackburn, 2012
Acidity
H+ + RO -
ROH
+ OH
+ OH
+ OH
OH
OH
-
-
O-
O-
O
O
O
-
-
© E.V. Blackburn, 2012
Substituent effects
O
OH
+ H+
G
G
An electron attracting substituent stabilizes the conjugate
base. The equilibrium is shifted to the right.
© E.V. Blackburn, 2012
Substituent effects
O
OH
G
+ H+
G
Electron donating substituents reduce the acidity of
phenols.
© E.V. Blackburn, 2012
Substituent effects
OH
CH3
OH
OH
NO 2
© E.V. Blackburn, 2012
Reaction with hydrogen
halides
ROH + HX
RX + H2O
HX: HI > HBr > HCl
ROH: allyl > 3 o > 2o > 1o < CH3OH
HBr or
CH3CHCH 3
OH
NaBr/H 2SO4
CH3CHCH 3
Br
© E.V. Blackburn, 2012
Experimental facts
1. The reaction is acid catalyzed
2. Rearrangements are possible
CH3 H
CH3 H
HCl
H3C C C CH3
H3C C C CH3
Cl H
H OH
3. Alcohol reactivity is 3o > 2o > 1o < CH3OH
© E.V. Blackburn, 2012
The mechanism
H+
C C
H
OH2
+
C C
H
OH
C C
H
OH2
+
C C
H +
C C
H +
+ H2O
C C
H
X
-
X
SN1
© E.V. Blackburn, 2012
Reaction of primary alcohols
with HX
1. ROH + HX
1o
+
2. ROH2 + X-
+
X
ROH 2 +
+
X R OH2
RX + H2O
SN2
HX:
HI > HBr > HCl
This reflects nucleophile strength in a protic solvent.
© E.V. Blackburn, 2012
Reactions with phosphorus
halides and with thionyl
chloride
ROH + PX3
RX + H3PO3
SN2
RCH2Cl + SO 2 + HCl
-
Cl
Creates a good leaving group from 1o and 2o alcohols.
© E.V. Blackburn, 2012
Tosylates
O
CH3CH2OH + Cl S
CH3
O
p-toluenesulfonyl
chloride
B: H O
+
O S
H3CH2C O
CH3
-
H +O
O S
H3CH2C O Cl
CH3
O
H3CH2CO S
CH3
O
ethyl p-toluenesulfonate
a tosylate
© E.V. Blackburn, 2012
Why form tosylates?
Sulfonate ions are excellent leaving groups:
Nu:
O
C O S
O
CH3
Nu C
O
O S
O
CH3
© E.V. Blackburn, 2012
Dehydration
H
C C
OH
OH
H3PO4

+ H 2O
H3PO4/
© E.V. Blackburn, 2012
Dehydration
H+
C C
H
OH
C C
H
OH2
+
B:
C C
H
OH2
+
C C
H +
C C
H +
+ H2O
C C
E1 mechanism
© E.V. Blackburn, 2012
Oxidation of primary alcohols
RCH2OH
O
C5H5NHCrO 3Cl
or K2Cr2O7
R
H
KMnO 4
or
K2Cr2O7
KMnO 4
C5H5NHCrO3Cl pyridinium
chlorochromate
in CH2Cl2 - PCC
O
R
OH
C5H5NHCrO 3Cl
CH3CH2C=O
CH3CH2CH2OH
CH2Cl2
H
© E.V. Blackburn, 2012
Oxidation of secondary
alcohols
+
C5H5NH CrO 3Cl, O
R2CHOH
K2Cr2O7,
CrO3, or
KMnO 4
R
R
R
CrO3
HOAc O
HO
3-cholestanol
3-cholestanone
© E.V. Blackburn, 2012
Synthesis of alcohols
alcohol
SOCl 2
Mg
alkyl halide
Grignard reagent
PCC
aldehyde
or ketone
CH3CH2OH
alcohol
CH3CHOHCH 2CH3
© E.V. Blackburn, 2012
Synthesis of alcohols
CH3CH2OH
CH3CH2OH
SOCl 2
CH3CH2Cl
PCC
CH3CH2OH
CH3CHOHCH 2CH3
Mg
CH3CH2MgCl
O
H3CC
H
O 1. CH3CH2MgCl
H3CC
CH3CHOHCH 2CH3
+
H 2. H3O
© E.V. Blackburn, 2012
Alcohols in synthesis
alcohol
H3PO4
HX
alcohol
alcohol
SOCl 2
alkene
Problems: carbocations form
and rearrangements can occur
in the E1 reaction
Problems: carbocations
form and rearrangements
alkyl halide can occur in the S 1
N
reaction.
KOH
alkyl halide
SN2 reaction - no
rearrangements
alkene
E2 reaction - no
rearrangements
© E.V. Blackburn, 2012
Synthesis of 3-methyl-1butene
KOH
H3C
H
H3C C C CH3
H
Br
acid
H3C
H
H3C C C CH3
H
OH
H 3C
CH3
C C
H 3C
H
H 3C
CH2
+ H 3C C C
H
H
© E.V. Blackburn, 2012
Synthesis of 3-methyl-1butene
H 3C
CH3
H3C
H
H3PO4
C C
H3C C C CH2OH
H 3C
H
H
H
H 3C
CH2
+ H 3C C C
H
H
© E.V. Blackburn, 2012
Synthesis of 3-methyl-1butene
H3C
H
H
SOCl 2 H3C
H3C C C CH2OH
H3C C C CH2Cl
H
H
H
H
H3C
CH2
H3C
H
KOH
H3C C C
H3C C C CH2Cl
H
H
H
H
SN2
E2
© E.V. Blackburn, 2012
Ethers
Structure:
R-O-R, Ar-O-R, or Ar-O-Ar
nomenclature
Name the two groups bonded to the oxygen and add
the word ether.
CH3CH2OCH2CH3 - diethyl ether
© E.V. Blackburn, 2012
Nomenclature of ethers
O
diphenyl ether
CH3OCH=CH2
O
CH(CH 3)2
CH3CH2CH2CHCH2CH3
|
OCH3
methyl vinyl ether
isopropyl phenyl ether
3-methoxyhexane
© E.V. Blackburn, 2012
Nomenclature of cyclic ethers
Use the prefix oxa- to indicate that an O replaces a CH2
in the ring.
oxacyclopropane
O
O
ethylene oxide
oxacyclopentane
tetrahydrofuran
O
1,4-dioxacyclohexane
O
1,4-dioxane
© E.V. Blackburn, 2012
Williamson synthesis
CH3Br + Na
+
CH3
O C CH3
CH3
CH3
H3C O C CH3
CH3
A primary halide is necessary to ensure an SN2 reaction
and not an E2 elimination.
© E.V. Blackburn, 2012
Reaction of ethers
O
CH3
HX
OH
+ CH3X
What is the mechanism?
© E.V. Blackburn, 2012
Epoxides
H3C
H
O
H
R
O OH
CH3 a peroxy
acid
H3C
H
O
H3C
H
trans-2,3-dimethyl
-oxacyclopropane
(E)-2-butene
syn addition
O
Cl
OOH
m-chloroperoxybenzoic acid
© E.V. Blackburn, 2012
Mechanism
+O
H
O
R
O
O R
O +
O
H
an oxirane
© E.V. Blackburn, 2012
Reactions
O
CH3OH/H
H
+
H
CH2OH
OCH3
What is the mechanism?
© E.V. Blackburn, 2012
© E.V. Blackburn, 2012

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