Download Alcohols, Ethers, and Epoxides

Org. Chem I Handout #8 ALCOHOLS, ETHERS AND EXPOXIDES General Summary: • Alcohols and ethers are not good electrophiles (they do not contain a good leaving group). • Must convert the hydroxyl group (in alcohols) or the alkoxy group (in ethers) into a good leaving group before substitution or elimination will occur • Epoxides are strained three‐membered cyclic ethers that are very reactive towards strong nucleophiles and acids due to significant ring‐strain. Preparation of alcohols: General Reaction
SN2
R X
-OH
+
X-
+
R-OH
Example
SN2
CH3CH2Br
-OH
+
CH3CH2OH
* Works with methyl, 1o and sometimes 2o alkyl halides
Preparation of ethers: General Reaction
SN2
R1 X
+
-OR
X-
+
R1-OR
better to use alkyl halides with
little or no sterics when you
have a choice
Example
I
NaH
OH
O- Na+
THF
+
O
SN2
NaI
alkoxide
formation
* Works with methyl, 1o and sometimes 2o alkyl halides
Preparation of epoxides: General Reaction
NaH
HO
Br
"halohydrin"
THF
-O
intramolecular
Br
O
SN2
Copyright © Doug E. Frantz The University of Texas at San Antonio Org. Chem I Handout #8 Dehydration of alcohol to synthesize alkenes: via strong acids:
strong acid
with weak nucleophilic
conjugate base
C C
H OH
Reactivity order = 3o > 2o > 1o
E1 pathway for 2o and 3o -carbocations are
intermediates with rearrangments possible
E2 pathway for 1o
Zaitsev rule applies to product formation
C C
Ex. H2SO4, H3PO4
TsOH
via POCl3:
POCl3
E2 pathway predominates
No carbocation rearrangments
C C
C C
H OH
N
pyridine
Synthesis of alkyl halides from alcohols: via strong acids:
Reactivity order = 3o > 2o > 1o
SN1 pathway for 2o and 3o -carbocations are intermediates
with rearrangments possible
SN2 pathway for 1o and CH3OH
Need to use ZnCl2 for conversion of 1o ROH to R-Cl
H-X
C C
H X
C C
H OH
* this reaction is truthfully only useful for tertiary alcohols. For 1o and 2o alcohols, use the reagents below
via specialized reagents:
SOCl2
C C
H OH
pyridine
C C
H Cl
Preferred method for methyl, 1o or 2o alcohols
These occur via an SN2 pathway.
PBr3
Make sure you know the mechanisms!!!
C C
H Br
C C
H OH
Don’t forget about using tosylates in substitution and elimination reactions as well. In many cases, they are better than their halide counterparts. Reaction of ethers and epoxides: R1 O R2
+
H-X
(2 equiv)
+
R1 X
R2 X
X = Br or I
Na+ -OCH3
true SN2
H3C
H3C
O
+
H2O
Mechanism for each product depends on
the nature of the alkyl group (i.e., 1o vs.
2o vs. 3o
This reaction is not very useful
synthetically
HO
HH
H3C
H3C
H
H
CH3OH
H3C
H2SO4
H3CO
OCH3
CH3
H
OH
H
with strong Nu:, an SN2 attack occurs at the
least sterically hindered carbon on the epoxide
with strong acids (i.e., HCl), the mechanism is
in between SN1 and SN2 and attack occurs at
the more substituted carbon
Copyright © Doug E. Frantz The University of Texas at San Antonio