Download CHEM 203 Topics Discussed on Nov. 25 Toxic and carcinogenic

CHEM 203
Topics Discussed on Nov. 25
Toxic and carcinogenic properties of Cr(VI) compounds – including CrO3
Electrophilic reactivity of metal-oxo linkages, Mt=O:
Mt = any metal
O
O
Nu:
nucleophiles add
Mt
Mt
easily to the metal
O
Mt
Nu
Pyridinium chlorochromate (PCC):
electrophilic
metal-oxo O
linkage
Cr
Cl
O VI O
chromium trioxide: a
common source of Cr (VI)
N
H
O
Cl Cr O
O
N
H
pyridinium
chloride
pyridinium chlorochromate
PCC oxidation of primary alcohols to aldehydes & secondary alcohols to ketones
R CH2 OH
O
generic
Cl Cr O
primary
VI
alcohol
O
substitution
of chloride
O
Hα
R C
H
R
O
H
an aldehyde
O
VI
Cr
O
O
± H+
Hα
O
VI
Cr
a special type
OH
O
R C
H
a chromate ester
H
IV OH
complex
O Cr
OH redox rxs.
+
O
of elim. react.
Cr(III) + Cr(VI)
a Cr(IV) complex
fine details of the mechanism of PCC oxidation remain unclear. The mechanism shown above
is one of a number of plausible mechanism that differ for the precise sequence of events leading
to the Cr(VI) complex that ultimately decomposes to give the carbonyl product.
OH
Likewise:
R1
2
H R
generic secondary alcohol
PCC
O
R1
R2
a ketone
The conversion of an alcohol into a carbonyl compound as an oxidation reaction
Lecture of Nov. 25
p. 2
overall:
oxid. st. = –1 if R2 = H
oxid. st. = 0 if R2 = alkyl
H
O
R1 C OH + Cl Cr O
VI
O
R2
oxid. st. = +1 if R2 = H
oxid. st. = +2 if R2 = alkyl
R
R1
C
2
O
+
O
O
IV OH
Cl
Cr
the OH-bearing C atom advances from the oxidation state of –1 or 0 to that of +1 or +2:
it undergoes a two-electron oxidation.
the Cr atom recedes from the oxidation state of +6 to that of +4:
it undergoes a two-electron reduction.
Inability of tertiary alcohols to undergo oxidation, due to the absence of α-H's
Conversion of chromium trioxide into chromic acid, H2CrO4 (the Cr analog of H2SO4)
O
electrophilic
metal-oxo
Cr
O VI O
linkage
H2O
O H
O Cr O
VI
H
O
O
HO Cr OH
VI
O
± H+
chromic acid: a
Cr(VI) compound
The Jones reagent: a solution of chromic acid, H2CrO4, in aqueous H2SO4:
O
electrophilic
metal-oxo
Cr
O VI O
linkage
H2O
O H
O Cr O
VI
H
O
± H+
O
the Jones reagent is
prepared by adding
HO Cr OH
VI
CrO3 to aq. H2SO4
O
chromic acid: a
Cr(VI) compound
IMPORTANT: PCC is used ONLY in anhydrous (=water-free) media, while Jones rgt. is an
aqueous solution. This seemingly minor difference has a major influence on the course of the
reaction of primary alcohols with the two reagents.
The Jones reagent: oxidation of primary alcohols to carboxylic acids and secondary alcohols to
ketones in aqueous medium
Reaction of the Jones reagent with primary alcohols: initial formation of a chromate ester:
R CH2
O
HO Cr OH
VI
OH
O
Hα
R C
H
O
OH
Cr OH
O
O
H
VI
±
H+
Hα
R C
H
O
OH
Cr OH
OH
O
VI
Reaction of the Jones reagent with primary alcohols: decomposition of the chromate ester to give
an aldehyde:
Lecture of Nov. 25
p. 3
O
Hα
R C
H
OH
Cr OH
OH
O
R
VI
O
H
an aldehyde
but the aldehyde is not the final product of the reaction (the carboxylic acid is): evidently,
something must happen to the aldehyde that causes it to become a carboxylic acid…
Acid-promoted equilibration of the aldehyde with a geminal diol in aqueous acid:
H
R
O
H
R
H O
H
O
H
H
O
H
H
H
O
R
very H
electrophilic
H
OH
H
O
OH
H
OH + H O
H
H
a geminal
("gem") diol
R
H
note: geminal diols (obtained by the reversible hydration of carbonyl functions)
display a pair of OH groups connected to the same carbon atom. Vicinal diols
(obtained by OsO4 oxidation of alkenes) have their OH groups connected to
adjacent carbon atoms:
R1
OH
C OH
HO OH
C C R4
R1
R2
R2 R3
a geminal diol: both OH groups
are attached to the same C atom
a vicinal diol: the OH groups are
attached to adjacent C atoms
(iii) further oxidation of the gem-diol to an acid by Cr(VI) through a second round of the
mechanism shown earlier:
OH
R CH OH
gem-diol
H2CrO4
"round II"
of Jones
mechanism
O
R C OH
[ + Cr(III) ]
carboxylic acid
Oxidation of secondary alcohols to ketones with the Jones reagent; e.g.:
R2
a generic
secondary R1 C
alcohol
H
O
HO Cr OH
OH
O
HO OH
HO O
+
Cr OH
Cr OH ± H
O
H O
O
O
R1 C
R1 C
H
H
R2
R2
+
R1
O
R2
a ketone
note: ketones can — and do — form geminal diols by reaction with H3O , but the geminal diol of
a ketone cannot undergo further oxidation because it has no α-H's
Lecture of Nov. 25
p. 4
Summary of the above oxidation reactions:
R–CH2–OH to R–CHO
possible only in a water-free medium: requires PCC
R–CH2–OH to R–COOH
possible only in an aqueous medium: requires Jones reagent
1
2
1
2
R R CH–OH to R R C=O
may be achieved with either PCC or Jones reagent
Principle: any carbonyl compound will equilibrate with the corresponding geminal (gem-) diol in
an aqueous acidic medium. However, gem-diols are thermodynamically disfavored relative to
carbonyls, and this primarily on entropic grounds. Therefore, any attempt to isolate gem-diols
will actually return the corresponding carbonyl compounds (at least as far as the carbonyl
compounds seen in CHEM 203 are concerned)
H
R1
O
R2
H
H O
H
O
R1
H
H
O
R2
H
H
R1
O
H
OH
O
R2
Overall ΔG slightly positive
H
R1
OH
OH
R2
a geminal
("gem") diol