Pyridinium o-iodoxybenzoate as a safe form of a famous oxidant

Article abstract of DOI:10.1016/j.mencom.2012.05.004

The stable pyridinium salt of o-iodoxybenzoic acid (PIBX) that is easy to obtain can serve as a convenient substitute of IBX as an oxidant. PIBX is safer, has neutral properties behaves as an equivalent to IBX in the oxidation of alcohols to ketones or aldehydes in polar solvents (DMF, DMSO), and provides higher oxidation rate in THF due to better solubility.

Full text of DOI:10.1016/j.mencom.2012.05.004

Mendeleev
Communications
Mendeleev Commun., 2012, 22, 129–131
Pyridinium o-iodoxybenzoate as a safe form of a famous oxidant
Ivan M. Kumanyaev, Margarita A. Lapitskaya, Ljudmila L. Vasiljeva and Kasimir K. Pivnitsky*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5328; e-mail: kpiv@mail.ru
DOI: 10.1016/j.mencom.2012.05.004
The stable pyridinium salt of o-iodoxybenzoic acid (PIBX) that is easy to obtain can serve as a convenient substitute of IBX as an
oxidant. PIBX is safer, has neutral properties behaves as an equivalent to IBX in the oxidation of alcohols to ketones or aldehydes in
polar solvents (DMF, DMSO), and provides higher oxidation rate in THF due to better solubility.
o-Iodoxybenzoic acid (existing as tautomer, viz. 1-hydroxy-
1-oxo-1H-1l5-benzo[d][1,2]iodoxol-3-one, IBX) finds an extensive
and ever-expanding application in synthetic organic chemistry as
a multi-purpose oxidant. IBX was first introduced in 1994 as a
convenient oxidant of alcohols to carbonyl compounds1 and has
since become a reagent of choice for dozens of oxidation pro-
cesses, which are often unique (see recent reviews2).
than IBX. Attempts to explode PIBX by impact (using a steel
hammer on a metal anvil) failed.
It has been known for a long time that IBX possesses a con-
siderable acidity and forms salts with metal cations.10 Recently,
pKaH O 2.40 was measured13 and the IBX tetra-n-butylammonium
2
salt was reported,14 which showed no oxidative properties. There-
fore, the formation of the pyridinium salt, i.e. PIBX, could not be
unexpected. The facility of PIBX preparative synthesis is due to
the high IBX solubility in pyridine (>100 mg cm–3) and the very
low solubility of the resulting PIBX (<2 mg cm–3). On the other
hand, we failed to obtain the IBX 2,6-dimethylpyridinium salt:
no changes occurred for three days in a suspension of IBX in
2,6-dimethylpyridine, despite the higher basicity of this amine
Though IBX is now often used in chemistry, two practical
problems have not been yet solved adequately. The first one is
practical insolubility of IBX in organic solvents except for dimethyl-
sulfoxide (DMSO). However, DMSO has low dissolving capacity
for lipophilic substrates and low volatility, which complicates
product isolation. In search for DMSO substitute, nearly all common
laboratory solvents were tested; of these, tetrahydrofuran3,4 (THF),
tert-butanol,5 ethyl acetate6 and dimethylformamide7,8 (DMF)
may be noted in particular. However, only in DMF oxidation of
alcohols was found to occur at room temperature at nearly the
same rate as in DMSO, owing to a considerable solubility of IBX
in DMF (up to 0.1 mol dm–3). In other solvents, this reaction
requires heating for several hours, which is often undesirable.
The potential explosiveness of IBX9 presents yet another
problem: it decomposes violently on heating above 200°C, which
is accompanied by a flame and a loud bang.2(c),10 For this reason,
IBX is commercially available only in a stabilised form (SIBX)11
as a mixture with benzoic and isophthalic acids containing 45%
IBX.12 Herein, we suggest a different solution of this problem.
While searching for a new solvent for IBX we tested pyridine.
An IBX suspension (280 mg) in dry pyridine (1 ml) at ambient
temperature (24–28°C) and with occasional superficial stirring
first undergoes slow (1–2 h) dissolution of a part of IBX to a con-
centration of ~100 mg cm–3, followed by faster precipitation of a
new compound as small colourless crystals, which ceased with
complete IBX dissolution in 12–24 h. Filtration with subsequent
washing of the crystals with pyridine (0.5 ml) and drying in vacuo
(1 Torr) gives 354 mg (99%) of IBX pyridinium salt (PIBX).†,‡
This salt remains unchanged on storage for three years in the
absence of bright light; slow heating results in its gradual decom-
position in the range of 200–255°C, leaving a dark non-melting
material. Upon fast heating, PIBX decomposes at 240°C with a
small clap and violet vapours but no flame. This behaviour on
heating characterises PIBX as a much more stable compound
(pKaH O 6.7215) in comparison with pyridine. This fact can be
2
attributed to the total insolubility of IBX in 2,6-dimethylpyridine.
PIBX is nearly insoluble in THF, MeCN, acetone, tert-butanol
and dichloromethane, highly soluble in DMSO and moderately
soluble in DMF (up to 0.19 mol dm–3)§ to give a neutral solution
(unlike that of IBX) which remains stable for a few days. NMR
spectra of a PIBX solution in DMSO-d6‡ are nearly a superposi-
tion of the spectra of IBX and pyridine. Dissociation of PIBX to
components is also observed upon keeping a PIBX suspension in
acetonitrile, when 35% of the precipitate is converted to IBX
in 24 h, while pyridine appears in the supernatant fluid. Such a
behaviour in solvents explains why the oxidative properties of
IBX are retained in PIBX, as we demonstrate here for several
hydroxyl-containing substrates (Table 1).¶
In all the examples presented in Table 1, in terms of all
parameters (oxidant excess, rate, yield), oxidation of substrates
by treatment with PIBX in DMF occurs almost identically to that
with IBX under the same conditions (see ref. 3 for substrates 1, 3, 5
and ref. 9 for substrate 7). The same picture is observed for sub-
†
The same results were obtained in numerous runs with scaling up, higher
amounts of pyridine, and vigorous stirring.
‡
PIBX: IR (KBr, n/cm–1): 696, 748, 784, 840, 1376, 1436, 1560, 1600,
1
3048, 3072, 3420. H NMR (300 MHz, DMSO-d6) d: 7.40 (dist.t, 2H,
2 Hb-Py), 7.78–7.86 (m, 2H, H-4, H-5), 7.97–8.05 (m, 2H, H-3, H-5), 8.15
(d, 1H, H-2, J 7.8 Hz), 8.58 (d, 2H, 2Ha-Py, J 4.3 Hz). 13C NMR (75 MHz,
DMSO-d6) d: 124.92, 130.07, 131.53, 132.90, 133.27, 146.63, 167.51 (all
for IBX), 124.04, 136.62, 149.27 (all for Py). Found (%): C, 40.23, 40.39;
H, 3.08, 3.02; I, 35.56, 35.66; N, 4.05, 3.95. Calc. for C12H10INO4 (%):
C, 40.13; H, 2.81; I, 35.64; N, 3.90.
O
O
§
OH
O
H
N
In this context, solubility is understood as the maximal amount of PIBX
I
I
Py
that dissolves completely in a given amount of the solvent. The solution
saturated with the excess of PIBX can possess a higher concentration
(with a pyridine:IBX ratio > 1) due to partial extraction of pyridine from
the undissolved PIBX fraction (see further). Low concentrations of pyridine
enhance the solubility of PIBX (or IBX) in organic solvents.
O
O
O
O
IBX
PIBX
© 2012 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2012, 22, 129–131
strates 9 and 12, whose oxidation with IBX occurs in anomalous
ways16 and the same anomalies are observed with PIBX.
Table 1 Oxidation of alcohols with PIBX in DMF at ambient temperature.
Entry Alcohola PIBX (equiv.) Time/h Productb
Yield (%)c
1
2
3
4
5
6
7
1
1
3
5
7
1.2
1.5
1.2
1.2
1.2
3g
4
24d
4
4
2.5
2
2
4
6
8
92
OH
O
Me
H
Me
H
95e
97
97
87f
H
H
PIBX
H
H
10 + 11 (2:1) 77h
MeO
MeO
9
12
24
4
1
2
1.6
13
97i
a See general procedure,¶ 0.1–1 mmol scale. bAll the products were individual
compounds as judged by TLC and NMR spectra (except for the binary mix-
ture in entry 6) and were identified by comparison with authentic samples
or (compounds 10,18 1116 and 13) spectral data.‡‡ c Isolated yields. d Reaction
in THF.†† e Under the same conditions, the reaction with IBX provides a 60%
conversion. f Partial loss of the volatile product during evaporation of solvents.
gWith addition of 3 Å molecular sieves (700 mg per mmol PIBX).19,§§ hThe
products had the same composition when IBX was used. i The same product
was formed with IBX.
O
Me
CH2OAc
OH
O
Me
CH2OAc
OH
HO
Me
O
H
Me
H
PIBX
H
H
H
H
O
O
3
4
CH2OH
CHO
A considerable difference between PIBX and IBX is observed
if THF is used as the solvent. With PIBX oxidation of alcohol 1
in THF is completed in 24 h, whereas IBX provides only a 60%
conversion within the same period of time.†† The nearly twice
faster reaction with PIBX is very likely to result from the higher
solubility of PIBX in organic solvents that in DMF is nearly twice
as high as that of IBX (see above).
PIBX
PIBX
5
6
Me
Me
Me
Me
Me
Me
Dissociation of PIBX on dissolution in DMSO allows us to
consider that an IBX solution in DMSO containing some pyridine
is equivalent to a PIBX solution. Such in situ generated PIBX was
already successfully used to perform various oxidative reactions of
IBX with acid-labile substrates or products where IBX acidity
caused or might cause side processes.17 In such cases, the use of the
neutral PIBX is beneficial.
To conclude, we suggest the readily available PIBX as a
convenient substitute for IBX, a widely-used oxidative reagent,
at least in the oxidation of alcohols to the corresponding carbonyl
compounds. In comparison with IBX, its pyridinium salt (PIBX)
is safer, has neutral properties and the same oxidizing ability in
polar solvents (DMF, DMSO) and, owing to its higher solubility,
has a superior oxidizing ability in THF and potentially in other
non-polar solvents.
CH2OH
CHO
7
8
Me
Me
O
Me
Me
Me
Me
O
O
O
O
O
OH
O
O
O
PIBX
+
O
O
O
O
O
O
O
O
O
Me
OH
Me
Me
Me
Me
Me
9
10
11
Me
Me
Me
Me
O
Me
H
Me
O
OH
Me
PIBX
H
Me
H
H
Me
References
AcO
O
12
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¶
General procedure (similar to the procedure of oxidation with IBX1).
1
Crystalline PIBX (1.2–3 molar equiv.) was added to a solution of an
alcohol in dry DMF (3–4 ml per mmol PIBX) and the suspension was
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DMF was replaced by THF.
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– 130 –

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Received: 22nd December 2011; Com. 11/3852
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