Carboxylic acids from primary alcohols and aldehydes by a pyridinium chlorochromate catalyzed oxidation

Article abstract of DOI:10.1055/s-2005-872085

A facile and quantitative preparation of carboxylic acids by a pyridinium chlorochromate (PCC) catalyzed (2 mol%) oxidation of primary alcohols and aldehydes using 2.2 equivalents and 1.1 equivalents of H₅IO ₆, respectively, in acetonitrile is described here. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872085

PAPER
2487
Carboxylic Acids from Primary Alcohols and Aldehydes by a Pyridinium
Chlorochromate Catalyzed Oxidation
Carboxylic
A
cids from
o
Primary Alcohols
Hand Aldehydes unsen*
Department of Chemistry, Kenyon College, Gambier, OH 43022, USA
Fax +1(740)4275731; E-mail: hunsenm@kenyon.edu.
Received 8 February 2005; revised 4 April 2005
PCC (2 mol%), H5IO6 (2.2 equiv)
MeCN
O
Abstract: A facile and quantitative preparation of carboxylic acids
by a pyridinium chlorochromate (PCC) catalyzed (2 mol%) oxida-
tion of primary alcohols and aldehydes using 2.2 equivalents and
1.1 equivalents of H5IO6, respectively, in acetonitrile is described
here.
R
OH
R
OH
Scheme 1
pothesized that the PCC/periodic acid combination may
form chlorochromatoperiodate16 that is possibly capable
of oxidations beyond what is possible by the individual re-
agents.
Key words: alcohols, aldehydes, oxidation, carboxylic acids, catal-
ysis, pyridinium chlorochromate (PCC), periodic acid
One the most fundamental reactions in synthetic organic
chemistry, oxidation, has been the subject of extensive
studies.1 Current methods for direct conversion of primary
alcohols to carboxylic acids include RuCl3/NaIO4,2 CrO3/
H2SO4,3 TEMPO/NaClO,4 Na2WO4/H2O2,5 and TEMPO/
NaClO2 in solution6 and solid7 phase. Alternatively,
To further study the scope and limitations of this PCC-cat-
alyzed oxidation, we have investigated the preparation of
carboxylic acids directly from primary alcohols and alde-
hydes and the results are reported here. Using only a cat-
alytic (2 mol%) amount of pyridinium chlorochromate
with 2.2 equivalents and 1.1 equivalents of H5IO6, for al-
cohols and aldehydes respectively, a clean and quantita-
tive conversion of primary alcohols and aldehydes to
carboxylic acids is achieved (Schemes 1 and 2).
9
Swern oxidation8 followed by NaClO2 or [CH3(n-
10
C8H17)3N]HSO4–H2O2 oxidation of the aldehyde could
deliver the carboxylic acid. Recently oxidation of (ho-
mo-)allylic and (homo-)propargylic alcohols to ketones
and carboxylic acids was achieved using Na2Cr2O7/
NaIO4.11 A CrO3-catalyzed12a periodic acid oxidation of
primary alcohols to carboxylic acids that works very well
for electron-poor benzylic alcohols is also reported. How-
ever, the CrO3-catalyzed oxidation gives complex mix-
tures when it comes to electron-rich benzylic and
homobenzylic alcohols. It also gives lower yields for ben-
zylic alcohols and fails for allylic and propargylic alco-
hols. In light of the importance of oxidation reaction in the
industry, there is still a need for new environmentally
friendly methods for direct oxidation of primary alcohols
to carboxylic acids especially in the presence of other
functional groups.
As shown in Table 1 various primary alcohols were oxi-
dized with PCC/H5IO6 to give the corresponding acids in
quantitative yields. Benzylic (entries 1, 4–7 and 10), ali-
phatic (entries 2 and 12) as well as homobenzylic (entries
3, 8, 9, and 11) alcohols oxidized smoothly in a short
amount of time. Electron-poor (entries 5 and 6) as well as
electron-rich (entry 4 and 7) benzyl alcohols were oxi-
dized without any problem. The electron-rich homoben-
zylic alcohols (entries 3, 8, and 9) were also oxidized
effortlessly. It is worth mentioning that unlike the CrO3
catalyzed12a oxidation, the PCC-catalyzed oxidation
works very well for benzylic alcohols as well as for elec-
tron-rich benzylic and homobenzylic alcohols. In addi-
tion, the naphthalene ring (entries 10 and 11) did not get
oxidized under the above-mentioned reaction conditions
PCC is one of the reagents of choice for oxidation of pri-
mary alcohols to aldehydes and secondary alcohols to ke-
tones.13,14 Unlike CrO3, PCC has a long shelf life and
better solubility in organic solvents. One of the major
problems in oxidation reactions using chromium is its car-
cinogenicity. Recently,15 we have shown that PCC can be
used catalytically to prepare aldehydes and ketones from
primary and secondary alcohols, respectively, using peri-
odic acid as the terminal oxidant. This is an environmen-
tally compatible oxidation since periodic acid is a
recyclable oxidant and less waste is generated. We hy-
12b
in contrast to the CrO3/H5IO6 oxidation. The aliphatic
diol (entry 12) cleanly oxidized to the a,w-dicarboxylic
acid without the formation of the lactone. It is also note-
worthy that in a control experiment where the reaction
was repeated under the same condition but in the absence
of PCC, no oxidation of benzyl alcohol to benzoic acid
was observed. Our attempt to oxidize an allylic alcohol
(cinnamyl alcohol) was not successful as it gave a com-
plex mixture.
In most of the cases no green coloration was observed as
the reaction progresses and no addition of water was re-
quired in contrast to the CrO3/H5IO6,12a oxidation. The py-
ridinium ion would help solubilize the oxidant. We
hypothesize that the mechanism may involve hydration of
SYNTHESIS 2005, No. 15, pp 2487–2490
x
x.
x
x
.
2
0
0
5
Advanced online publication: 20.07.2005
DOI: 10.1055/s-2005-872085; Art ID: M00905SS
© Georg Thieme Verlag Stuttgart · New York

2488
M. Hunsen
PAPER
the aldehydes that would form under the reaction condi- all oxidized cleanly. Benzaldehyde (entry 3) as well as
tion with H2O (that forms when H5IO6 is converted to electron-rich (entry 4 and 7), and electron-poor (entries 5,
HIO3 and H2O) to generate the carboxylic acids.
6, 8, and 9) benzaldehydes also oxidized effortlessly to
deliver the carboxylic acids quantitatively.
Next, we investigated the oxidation of aldehydes to car-
boxylic acids (Scheme 2). The oxidation of aldehydes was We have also studied this oxidation reaction using water
completed in a shorter time and the clean carboxylic acids as a solvent. Using 2 mol% PCC and a phase transfer cat-
were obtained quantitatively. The only difference from alyst (tetrabutylammonium iodide) in water we have
the procedure given below for the oxidation of primary al- quantitatively oxidized benzyl alcohol and benzaldehyde
cohols was that the reaction time was 90 minutes and the to benzoic acid (data not shown) with 2.3 equivalents and
amount of periodic acid, which was 1.1 equivalents. As 1.2 equivalents of periodic acid, respectively. Although
shown in Table 2, aliphatic (entries 1, 2, and 10) as well the reaction was much slower (48 h), the work up was
as propargylic (entry 11), and vinyl (entry 12) aldehydes much easier involving just filtering the water insoluble
a
Table 1 Oxidation of Primary Alcohols to Carboxylic Acids with PCC/H5IO6
Entry
Substrate
Product
Yieldb (%)
CO2H
1
2
3
4
96
99
99
98
Ph
Ph
Ph
OH
CO2H
OH
OH
Ph
CO2H
CO2H
OH
H3C
H3C
5
6
7
98
99
97
CO2H
OH
Cl
Cl
CO2H
OH
O2N
O2N
CO2H
OH
H3CO
H3CO
H3CO
H3CO
8
9
99
98
96
CH2OH
CO2H
CH2OH
CH3
CH2OH
CO2H
CH3
10
CO2H
11
12
97
98
CH2OH
CO2H
OH
OH
CO2H
CO2H
a The reactions were conducted in MeCN using H5IO6 (2.2 equiv) and PCC (2 mol%). The products were characterized by comparing their
NMR spectra with those reported by Aldrich and with authentic samples.
b NMR spectra of the products showed only the desired products and no unreacted starting material was observed.
Synthesis 2005, No. 15, 2487–2490 © Thieme Stuttgart · New York

PAPER
Carboxylic Acids from Primary Alcohols and Aldehydes
2489
O
carboxylic acid and washing the product with saturated
aqueous NaHSO3 solution and water. Using water as a
solvent is a greener process as no organic solvent was
used during the reaction and work up. Further investiga-
tion on catalytic oxidations in the aqueous phase is in
progress and will be reported in due course.
H
PCC (2 mol%), H5IO6 (1.1 equiv)
MeCN
R
O
R
OH
Scheme 2
Synthesis of Benzoic acid (Table 1, Entry 1); Typical Procedure
To MeCN (40 mL) was added H5IO6 (2.50 g, 11 mmol) and the mix-
ture was stirred vigorously at r.t. for 15 min. Benzyl alcohol (0.54
g, 5 mmol) was then added (in ice-water bath) followed by addition
of PCC (22 mg, 2 mol%) in MeCN (2 × 5 mL) and the reaction mix-
ture was stirred for 3 h. The reaction mixture was then diluted with
EtOAc (100 mL) and washed with brine–water (1:1), sat. aq
NaHSO3 solution, and brine, respectively, dried over anhyd Na2SO4
and concentrated to give the clean carboxylic acid (0.59 g, 96%
yield).
In conclusion, we have shown for the first time that pyri-
dinium chlorochromate efficiently catalyzes the oxidation
of primary alcohols directly to carboxylic acids using
periodic acid as the co-oxidant. This procedure affords the
acids in quantitative yields in a short amount of time. We
have also shown that aldehydes can be quantitatively oxi-
dized in a shorter amount of time using only 1.1 equiva-
lents of periodic acid and a catalytic amount of PCC.
a
Table 2 Oxidation of Aldehydes to Carboxylic Acids with PCC/H5IO6
Entry
1
Substrate
Product
Yieldb (%)
97
CO2H
CHO
4
4
2
95
CO2H
CHO
3
4
98
99
H
OH
Ph
O
Ph
O
CHO
CO2H
H3C
H3C
5
6
7
8
9
95c
95
97
96
99
CHO
CO2H
CO2H
Cl
Cl
CHO
O2N
O2N
CHO
CO2H
H3CO
H3CO
CO2H
CO2H
CHO
Br
Br
O2N
CHO
O2N
10
11
97
CHO
CHO
CO2H
CO2H
96d
12
43e
CHO
CO2H
a The reactions were conducted in MeCN using H5IO6 (1.1 equiv) and PCC (2 mol%) for 1.5 h. The products were characterized by comparing
their NMR spectra with those reported by Aldrich and with authentic samples.
b NMR spectra of the products showed only the desired products unless otherwise noted.
c Three percent starting material was left unreacted.
d Two percent starting material was left unreacted.
e Some of the product is lost during workup due to its water solubility.
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M. Hunsen
PAPER
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Acknowledgment
MH thanks Kenyon College for the generous start up fund.
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Synthesis 2005, No. 15, 2487–2490 © Thieme Stuttgart · New York