A User-Friendly Entry to 2-Iodoxybenzoic Acid (IBX)

Full text of DOI:10.1021/jo9824596

J . Org. Chem. 1999, 64, 4537-4538
4537
selective oxidation of 1,4-diols to γ-lactols6 and the
oxidative ring closure of amino alcohols to aminals. A
more recent protocol reports the easy regeneration of
carbonyl compounds from oximes or tosylhydrazones by
IBX.8
A User -F r ien d ly En tr y to 2-Iod oxyben zoic
Acid (IBX)
7
Marco Frigerio, Marco Santagostino,* and
Simona Sputore
9
a,b
Although numerous syntheses of IBX from 2-iodo
Prassis Istituto di Ricerche Sigma-Tau, Via Forlanini 3,
or 2-iodosobenzoic9 acid have been described over the
years; in most cases, the reported procedures deliver a
reagent of poor quality that requires tedious purification.
c,d
2
0019 Settimo Milanese, Milano, Italy
Received December 16, 1998
1
0a
In this light, the Greenbaum procedure and subsequent
IBX, 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (2-
iodoxybenzoic acid 1), has been known for more than a
century, although its presence on the scene of organic
synthesis has remained limited primarily due to its
remarkable insolubility in most organic solvents.1
modifications2
a,10b,c
stand as significant improvements,
giving optimal yields and somewhat better purity, and
represent the state-of-the-art procedure for IBX synthe-
sis. However, these KBrO
unappealing for the user in that the reaction is performed
in hot aqueous sulfuric acid (0.73 M), KBrO is classified
3
-based oxidation methods are
,2b,3a
3
as a carcinogen (R-45) in the international classification
of substance toxicity, and obnoxious bromine vapors are
copiously evolved (62 g/mol of IBX) from the reaction
mixture, with personal and environmental contamination
risk. Still, incomplete oxidation of 2-iodobenzoic acid is
not totally avoided and recovered IBX is contaminated
1
1
with variable amounts of less-oxidized precursors.
We have now found that the use of Oxone (2KHSO
KHSO -K SO ) provides a practical entry to IBX. The
oxidation was complete in 3 h in water at 70-75 °C,
5
-
4
2
4
1
2
with 1.3 equiv of oxone (using a 0.44 M solution). IBX
was recovered easily from the reaction mixture in high
yields (79-81%) and good purity (g95%) by cooling,
filtering, and washing the crystals with water and
acetone. Moreover, by using a greater dilution and excess
oxone (3 equiv), a clear solution was obtained after 1 h
at 70 °C from which IBX crystallized upon cooling, free
from any reduced contaminant in 77% yield. This new
procedure offers distinct advantages over the previous
ones: (i) experimental convenience, since it uses a
nontoxic reagent and water as solvent, (ii) environmen-
tally safe sulfate salts as the only byproducts, and (iii)
easy adaptation of the method to produce analytically
pure (g99%, NMR) samples of IBX.
In 1983, Dess and Martin reported that IBX could be
transformed into the far more soluble periodinane 2,
1
,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one, by
2
warming 1 in an acetic anhydride-acetic acid mixture.
Since then, the Dess-Martin periodinane has met with
remarkable success for the smooth and selective trans-
formation of alcohols into carbonyl compounds.2b
Besides its use as the Dess-Martin periodinane pre-
cursor, IBX itself functions as a valuable oxidant of
functionalized alcohols when dissolved in DMSO or
The experimental procedure detailed below has been
performed several times, by different operators, to pro-
3
suspended in other solvents. A number of applications
of the reagent have emphasized its generality as a mild
4
oxidizing agent as well as its ability to perform delicate
(6) Corey, E. J .; Palani A. Tetrahedron Lett. 1995, 36, 3485. Corey,
transformations. In particular, IBX oxidizes vic-diols
E. J .; Palani A. Tetrahedron Lett. 1995, 36, 7945.
without cleaving the glycol C-C bond3a,5 and allows the
(7) Bose, D. S.; Srinivas, P.; Gurjar, M. K. Tetrahedron Lett. 1997,
3
8, 5839.
(
8) Bose, D. S.; Srinivas, P. Synlett 1998, 977.
(1) Hartman, C.; Meyer, V. Chem. Ber. 1893, 26, 1727.
2
(9) (a) Cl /NaOCl: Bell, R.; Morgan, K. J . J . Chem. Soc. 1960, 1209.
(
2) (a) Dess, B. D.; Martin, J . C. J . Org. Chem. 1983, 48, 4155. (b)
(b) Cl
1989, 27, 1007. (c) KMnO
Chem. Ber. 1894, 27, 1600.
2
: Katritzky, A. R.; Duell, B. L.; Gallos, J . K. Org. Magn. Reson.
Dess, B. D.; Martin, J . C. J . Am. Chem. Soc. 1991, 113, 7277 and
references therein. Improved protocols for the preparation of 2 from 1
have been reported: (c) Ireland, R. E.; Liu, L. J . J . Org. Chem. 1993,
8, 2899. (d) Meyer, S. D.; Schreiber, S. L. J . Org. Chem. 1994, 59,
549.
4
:
ref 1. (d) Cl Hartman, C.; Meyer, V.
2
:
(10) (a) Greenbaum, F. R. Am. J . Pharm. 1936, 108, 17. (b) Banerjee,
A.; Banerjee, G. C.; Bhattacharya, S.; Banerjee, S.; Samaddar, H. J .
Ind. Chem. Soc. 1981, 58, 605. (c) An improved procedure for the
preparation of IBX and the Dess-Martin periodinane, which is a
5
7
(
3) (a) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35,
8
019. (b) Frigerio, M.; Santagostino, M.; Sputore S.; Palmisano, G. J .
3 2 4
modification of the classic KBrO /H SO procedure, is in press
Org. Chem. 1995, 60, 7272. (c) De Munari, S.; Frigerio, M.; Santagos-
tino, M. J . Org. Chem. 1996, 61, 9272.
(Boeckman, R. K., J r.; Shao, P.; Mullins, J . J . Org. Synth.).
(11) We have prepared several 5-200 g batches of IBX (75-85%
2
b
(4) For some recent examples, see: Breuilles, P.; Uguen, D. Tetra-
yield) according to the Dess-Martin procedure. The purity of the
reagent varied between 90 and 95%, the major contaminants being
2-iodobenzoic acid (1-3%) and 2-iodosobenzoic acid (5-10%).
(12) Working at higher temperature (95-100 °C) is not advisable
since IBX is consistentely reduced to 2-iodosobenzoic acid under these
conditions; for the same reason, recrystallization from pure water (at
75 °C, 1.0 g of IBX 98% in 60 mL) is unapplicable since the procedure
yields a product (56% yield) of decreased purity (90% of IBX, 7% and
3% of 2-iodoso and 2-iodobenzoic acid, respectively).
hedron Lett. 1998, 39, 3149. Varadarajan, S.; Mohapatra, D. K.; Datta,
A Tetrahedron Lett. 1998, 39, 1075. Hulme, A. N.; Howells, G. E.
Tetrahedron Lett. 1997, 38, 8245. Pearson, W. H.; Clark, R. B.
Tetrahedron Lett. 1997, 38, 7669. Andrus, M. B.; Shih, T.-L. J . Org.
Chem. 1996, 61, 8780. Boehm, T. L.; Showalter, H. D. H. J . Org. Chem.
1
996, 61, 6498.
5) Frigerio, M.; Santagostino, M.; Sputore, S. Synlett 1997, 833.
Hegde, S. G., Myles D. C. Tetrahedron Lett. 1997, 38, 4329.
(
1
0.1021/jo9824596 CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/14/1999

4
538 J . Org. Chem., Vol. 64, No. 12, 1999
Notes
vide 45-50 g batches of IBX with reproducible yields and
purity.
rinsed with water (6 × 100 mL) and acetone (2 × 100 mL). The
white, crystalline solid was left to dry at rt for 16 h and weighed
4
4.8-45.7 g (79-81%).
Mother and washing liquors were oxidizing and acidic. They
were treated with solid Na SO (70 g, 0.55 mol) and neutralized
2 3
Exp er im en ta l Section
with NaOH (1 M) before disposal. The internal temperature rose
to 30 °C.
CAUTION! IBX is explosive under impact or heating to >200
1
3
°
C. Sporadically, IBX did not decompose explosively at 233 °C,
1
The purity of IBX obtained by this method was g95% ( H
NMR, elemental analysis). The remainder was 2-iodosobenzoic
but melted with browning. However, this cannot be taken as an
indication of absence of explosivity since the same batch showed
inconsistent results. An analytically pure sample (g99%) was
subjected to explosibility tests, which confirmed the earlier
(
4%) and 2-iodobenzoic (∼0.5%) acids, as judged by integration
1
of the triplets at 7.70 and 7.47 ppm, respectively, in the H NMR
1
3
spectrum (ca. 5 mg in 0.5 mL of DMSO-d
Mp: 233 °C dec (lit.2b mp 232-233 °C). Anal. Calcd for C
: C, 30.03; H, 1.80; I, 45.32. Found: C, 30.16; H, 1.82; I, 45.32.
6
).
observations by Plumb and Harper.
5
H -
Reagents were commercially available and were used without
further purification. Reactions were conducted in an open flask.
Elemental analyses and water (Karl Fisher) determination were
carried out by Redox, Cologno Monzese (Milano, Italy).
IBX, 1-Hyd r oxy-1,2-ben ziod oxol-3(1H)-on e 1-Oxid e (1)
7
IO
4
1
13
H O <0.1% (K.F.). H NMR, C NMR, and IR spectra all agree
2
3a
with those previously reported.
1
IBX (g99% purity, H NMR, elemental analysis) was similarly
prepared by adding 2-iodobenzoic acid (5.0 g, 0.020 mol) to an
Oxone solution in deionized water (37.2 g, 0.061 mol, 3 equiv in
200 mL) in a 0.5 L flask. The suspension was set to 70 °C; after
1 h at this temperature a clear solution was obtained that
delivered analytical grade IBX upon cooling the solution to 0-5
°C for 0.5 h and filtering and washing the crystals as described
before (4.4 g, 77%).
(
g95% P u r ity). 2-Iodobenzoic acid (50.0 g, 0.20 mol) was added
all at once to a solution of Oxone (181.0 g, 0.29 mol, 1.3 equiv)
in deionized water (650 mL, 0.45 M) in a 2 L flask. The reaction
mixture was warmed to 70-73 °C over 20 min and mechanically
stirred at this temperature for 3 h. The aspect of the mixture
varies consistently during the reaction. The initial thick slurry
coating the walls of the flask eventually becomes a finely
dispersed, easy to stir suspension of a small amount of solid that
sedimented easily upon stopping the stirring. The suspension
was then cooled to 5 °C and left at this temperature for 1.5 h
with slow stirring. The mixture was filtered through a medium
porosity sintered-glass funnel, and the solid was repeatedly
Mp: 233 °C dec. Anal. Found: C, 30.02; H, 1.77; I, 45.09. H O
2
<0.1% (K.F.).
Ack n ow led gm en t. Appreciation is expressed to Dr.
Piero Melloni for supporting this work.
(13) Plumb, J . B.; Harper, D. J . Chem. Eng. News 1990, J uly 16, 3.
J O9824596