Download CHEM 203 Topics Discussed on Nov. 20 Principle: protonation of

CHEM 203
Topics Discussed on Nov. 20
Principle: protonation of alcohols transforms the OH group into an incipient molecule of H2O,
which is the conjugate base of a strong Bronsted acid, H3O+ (pKa ≈ –2). So, H2O can function as
a leaving group in SN2/SN1 or E2/E1 reactions (cf. the case of ethers; notes of Nov. 16)
Note: the OH group per se cannot function as a leaving group in SN2/SN1 or E2/E1
–
reactions, because then it would have to leave as HO , which is the conjugate base
of the weak acid, H2O (pKa≈16). Recall that only conjugate bases of strong acids
(pKa<0) can function as leaving groups in such reactions (notes of Oct. 28).
Reactions in which a protonated alcohol undergoes nucleophilic substitution of H2O:
Reactions of alcohols with H–X: formation of alkyl halides:
H–X
R–OH
R–X
primary, secondary
or tertiary alcohol
primary, secondary
or tertiary alkyl halide
X = Cl, Br, I
for a primary alcohol, e.g., 1-butanol:
Br
Br
H–Br
OH
OH2
primary: backside readily accessible
reacts by SN2 mechanism
for a tertiary alcohol, e.g., tert-butanol:
H2O
Cl
H–Cl
OH
Cl
OH2
Cl
tertiary: backside inaccessible
reacts by SN1 mechanism
for a secondary alcohol, e.g., (S)-2-butanol:
I
H–I
H
OH
H
OH2
I
alkyl halide may forms
with partial erosion of
stereochemical purity
secondary: backside fairly accessible
tends to react partly by SN2 and partly by SN1 mechanism: precise
extent of SN2 / SN1 reactivity depends on structure and conditions
Principle: alkyl halides are best prepared from alcohols
Lecture of Nov 20
p. 2
Potential usefulness of halogenation reagents that might permit the conversion of secondary
alcohols into secondary halides in a stereochemically unequivocal manner (= 100% inversion or
100% retention of configuration)
Phosphorus and sulfur halides that convert alcohols to alkyl halides in a stereochemically clean
manner: phosphorus trichloride / tribromide (PCl3, PBr3), thionyl chloride (SOCl2)
Electrophilic character of the above reagents and facile reaction thereof with nucleophiles
Principle: the above reagents rely on the nucleophilic properties of the OH group to achieve
conversion of alcohols into alkyl halides
Principle: only primary and secondary alcohols are sufficiently nucleophilic to react with the
above reagents. The OH group of tertiary alcohols is poorly nucleophilic due to steric hindrance:
PCl3 or
OH
PCl3 or
OH
X
X
X = Cl, Br
X = Cl, Br
PBr3 or
SOCl2
PBr3 or
SOCl2
PCl3 or
OH
little / no alkyl
halide formation
PBr3 or
SOCl2
Inversion of configuration during the reaction of secondary alcohols with the above reagents:
H
PBr3
Br
H
OH
PCl3 or
H
Cl
SOCl2
Probable mechanism of the conversion of primary / secondary alcohols to alkyl bromides with,
e.g., PBr3 (PCl3 reacts in the same fashion):
R1
R2
H
C
OH
Br
Br
P
similar to an
Br
R1
Br
SN2 reaction
R1
R2
Br
C
H
+
R2
H
Br
C
O P
Br
H
SN2
rx.
Br
O P
Br
H
notice inversion of config.
at the carbon atom
note:
HO–PBr2 still posseses P–Br bonds, so it may undergo a 2nd and a 3rd round of the
same reaction, ultimately producing phosphorous acid, P(OH)3
Lecture of Nov 20
p. 3
Probable mechanism of the conversion of primary and secondary alcohols into alkyl chlorides
with SOCl2:
Cl
R1
R2
H
C
OH Cl
O
S
Cl
a substitution
R1
reaction
R2
H
C
Cl
O
an SN2
R1
O
C
+
O S
O S
Cl
R2 H
reaction
H
Cl
H
note: this step proceeds
decomposes
with inversion of config.
rapidly to HCl + SO2
at the carbon atom