Esters of 2-iodoxybenzoic acid: Hypervalent iodine oxidizing reagents with a pseudobenziodoxole structure

Article abstract of DOI:10.1021/jo051010r

Esters of 2-iodoxybenzoic acid (IBX-esters) were prepared by the hypochlorite oxidation of the corresponding 2-iodobenzoate esters and isolated as chemically stable, microcrystalline products. These hypervalent iodine compounds are potentially valuable ox

Full text of DOI:10.1021/jo051010r

Esters of 2-Iodoxybenzoic Acid: Hypervalent Iodine Oxidizing
Reagents with a Pseudobenziodoxole Structure
,
†
†
†
‡
Viktor V. Zhdankin,* Alexey Y. Koposov, Dmitry N. Litvinov, Michael J. Ferguson,
‡
‡
‡
Robert McDonald, Thanh Luu, and Rik R. Tykwinski
Department of Chemistry, University of MinnesotasDuluth, Duluth, Minnesota 55812, and Department of
Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 Canada
vzhdanki@d.umn.edu
Received May 20, 2005
Esters of 2-iodoxybenzoic acid (IBX-esters) were prepared by the hypochlorite oxidation of the
corresponding 2-iodobenzoate esters and isolated as chemically stable, microcrystalline products.
These hypervalent iodine compounds are potentially valuable oxidizing reagents belonging to a
new class of pentavalent iodine compounds with a pseudobenziodoxole structure. Methyl 2-iodoxy-
benzoate can be further converted to the diacetate or a bis(trifluoroacetate) derivative by treatment
with acetic anhydride or trifluoroacetic anhydride, respectively. Single-crystal X-ray diffraction
analysis of methyl 2-[(diacetoxy)iodosyl]benzoate 8a reveals a pseudobenziodoxole structure with
three relatively weak intramolecular I‚‚‚O interactions. The dimethyl and diisopropyl esters of
2-iodoxyisophthalic acid were prepared by oxidation of the respective iodoarenes with dimethyl-
dioxirane. Single-crystal X-ray diffraction analysis of diisopropyl 2-iodoxyisophthalate 6b showed
intramolecular I‚‚‚O interaction with the carbonyl oxygen of only one of the two carboxylic groups,
while NMR spectra in solution indicated equivalency of both ester groups. IBX-esters, methyl
2
-[(diacetoxy)iodosyl]benzoate, and 2-iodoxyisophthalate esters can oxidize alcohols to the respective
aldehydes or ketones in the presence of trifluoroacetic acid or boron trifluoride etherate. The bis-
trifluoroacetate) derivative can oxidize alcohols to carbonyl compounds without acid catalyst.
(
Introduction
acid (IBX) (structure 1b), although the tautomeric form
a gives the correct representation for the actual struc-
1
In the past decade, the chemistry of hypervalent iodine
ture of this compound. This has been confirmed by X-ray
crystallographic analysis, which also indicates a poly-
meric structure for IBX due to an extended linkage of
3
5
compounds (λ - and λ -iodanes) has experienced an
1
unprecedented growth. A broad variety of polyvalent
iodine reagents have been prepared, and new, highly
useful synthetic procedures have been developed. Hy-
pervalent iodine reagents based on the heterocyclic
system of benziodoxole represent an especially important
class of iodanes with rich and synthetically useful
4
intermolecular secondary I‚‚‚O bonding interactions. The
(1) (a) Varvoglis, A. The Organic Chemistry of Polycoordinated
Iodine; VCH Publishers: New York, 1992. Varvoglis, A. Hypervalent
Iodine in Organic Synthesis; Academic Press: London, 1997. (b) Koser,
G. F. In The Chemistry of Halides, Pseudo-Halides and Azides, Suppl.
D2; Patai, S., Rappoport, Z., Eds.; Wiley-Interscience: Chichester,
1995; Chapter 21, pp 1173-1274. Koser G. F. Aldrichim. Acta 2001,
1
-3
5
chemistry.
In particular, the heterocyclic λ -iodane,
5
1
-hydroxy-1-oxo-1H-1λ -benzo[d][1,2]iodoxol-3-one (1a),
3
4, 89. Koser, G. F. Adv. Heterocycl. Chem. 2004, 86, 225-292.
has received widespread application in organic synthesis
as a highly efficient and mild oxidant that can be used
for selective oxidation of primary and secondary alcohols
and for a variety of other important oxidations.1
Reagent 1a is commonly referred to as 2-iodoxybenzoic
(c) Moriarty, R. M.; Prakash, O. Adv. Heterocycl. Chem. 1998, 69, 1-87.
Moriarty, R. M.; Prakash, O. Org. React. 1999, 54, 273-418. Moriarty,
R. M.; Prakash, O. Org. React. 2001, 57, 327-415. (d) Morales-Rojas,
H.; Moss, R. A. Chem. Rev. 2002, 102, 2497-2521. (e) Zhdankin, V.
V.; Stang, P. J. Chem. Rev. 2002, 102, 2523-2584. (f) Zhdankin, V. V.
Rev. Heteroatom Chem. 1997, 17, 133-152. (g) Wirth, T.; Hirt, U. H.
Synthesis 1999, 1271-1287. Wirth, T. Angew. Chem., Int. Ed. 2001,
-3
4
0, 2812-2814. (h) Hypervalent Iodine Chemistry. In Topics in Current
†
University of MinnesotasDuluth.
Chemistry; Wirth, T., Ed.; Springer-Verlag: Berlin Heidelberg, 2003;
Vol. 224.
‡
University of Alberta.
10.1021/jo051010r CCC: $30.25 © 2005 American Chemical Society
6484
J. Org. Chem. 2005, 70, 6484-6491
Published on Web 07/07/2005

Esters of 2-Iodoxybenzoic Acid
CHART 1. IBX and Its Derivatives
SCHEME 1
preparation of the polymer-supported IBX-esters and
IBX-amides, which showed excellent oxidative activity
toward benzylic alcohols and were also used for oxidative
bromination of activated arenes.9
In the present work, we report details on the prepara-
tion and chemistry of IBX-esters 4 as well as the
preparation and structure of two new iodoxybenzoate
derivatives, namely, diacetate derivatives of IBX-esters
polymeric structure of IBX renders it essentially insoluble
in all nonreactive media. The low solubility of IBX and
its potentially explosive nature restrict practical applica-
tion of this valuable reagent. Several research groups
(
5) and diesters of 2-iodoxyisophthalic acid (6).
1,5
have tried to improve IBX by structurally modifying it
Results and Discussion
6
or by developing polymer-supported analogues. The most
important derivative of IBX is the commercially available
triacetate 2, commonly known as Dess-Martin perio-
Preparation of IBX-Esters. Iodoxybenzoates 4a-j
1
0
were prepared by the hypochlorite oxidation of the
respective esters of 2-iodobenzoic acid 7a-j in the pres-
ence of acetic acid and dichloromethane (Scheme 1). The
methyl and ethyl esters 4a and 4b, being essentially
insoluble in dichloromethane, precipitated from the reac-
tion mixture and were isolated by filtration in the form
of white, microcrystalline solids. All other esters 4c-j
were extracted from the reaction mixture with dichlo-
romethane and obtained as colorless or pale-yellow
amorphous solids or oils after solvent evaporation. Crys-
tallization of crude products from acetonitrile furnished
products 4c-j in white, microcrystalline form, which
could be converted back into the amorphous form by
1
dinane (DMP). DMP is prepared by heating IBX with
acetic anhydride, and it has improved solubility compared
to IBX. It is, however, moisture sensitive, which imposes
certain restrictions on storage and handling of this useful
reagent. Recently, we have reported the synthesis and
structural analysis of amides and esters of 2-iodoxy-
7
8
benzoic acid, IBX-amides (3), and IBX-esters (4), which
are stable and soluble reagents having oxidizing proper-
ties similar to IBX. According to X-ray data, these new
derivatives of IBX have a pseudobenziodoxole structure
due to iodine-oxygen secondary bonding interactions. In
comparison with IBX and other benziodoxoles, pseudo-
benziodoxoles have much better solubility, which is
explained by a partial disruption of their polymeric
nature due to the redirection of I‚‚‚O secondary bond-
2 2
dissolving the crystals in CH Cl followed by solvent
evaporation. An alternative procedure for the hypo-
chlorite oxidation of 2-iodobenzoate esters 7 involves the
use of dry ice instead of acetic acid in order to simplify
extraction and purification of products 4. This modifica-
tion works especially well for the preparation of the
isopropyl ester 4c. By use of either workup protocol, the
hypochlorite oxidation procedure allows for the prepara-
tion of iodoxybenzoate esters 4 derived from a wide
variety of precursors, including primary, secondary, and
tertiary alcohols, adamantanols, as well as optically
active menthols and borneol. Preparative yields of pure
products 4 are generally in the range 60-90%, with the
exception of the methyl ester 4a, which was isolated in
a low yield (21%) due to its solubility in the aqueous
phase of the reaction mixture. In general, products 4c-j
have moderate to high solubility in common organic
solvents, such as chloroform, dichloromethane, and aceto-
nitrile. In dichloromethane, for example, the solubilities
7
,8
ing. Very recently, Lee and co-workers reported the
(
2) Zhdankin, V. V. Curr. Org. Synth. 2005, 2, 121-145.
(
3) Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. J. Am. Chem.
Soc. 2004, 126, 5192. Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Sugita,
K. J. Am. Chem. Soc. 2002, 124, 2212 and references therein.
(
4) (a) Stevenson, P. J.; Treacy, A. B.; Nieuwenhuyzen, M. J. Chem.
Soc., Perkin Trans. 2 1997, 589. (b) Gougoutas, J. Z. Cryst. Struct.
Commun. 1981, 10, 489.
(
5) (a) Thottumkara, A. P.; Vinod, T. K. Tetrahedron Lett. 2002, 43,
5
69. (b) Zhdankin, V. V.; Smart, J. T.; Zhao, P.; Kiprof, P. Tetrahedron
Lett. 2000, 41, 5299. (c) Ozanne, A.; Pouysegu, L.; Depernet, D.;
Francois, B.; Quideau, S. Org. Lett. 2003, 5, 2903.
(6) (a) M u¨ lbaier, M.; Giannis, A. Angew. Chem., Int. Ed. 2001, 40,
4
393. (b) Mulbaier, M.; Giannis, A. ARKIVOC 2003, 228. (c) Sorg, G.;
Mengel, A.; Jung, G.; Rademann, J. Angew. Chem., Int. Ed. 2001, 40,
395. (d) Reed, N. N.; Delgado, M.; Hereford, K.; Clapham, B.; Janda,
4
K. D. Bioorg. Med. Chem. Lett. 2002, 12, 2047. (e) Lei, Z.; Denecker,
C.; Jegasothy, S.; Sherrington, D. C.; Slater, N. K. H.; Sutherland, A.
J. Tetrahedron Lett. 2003, 44, 1635.
(
7) Zhdankin, V. V.; Koposov, A. Y.; Netzel, B. C.; Yashin, N. V.;
Rempel, B. P.; Ferguson, M. J.; Tykwinski, R. R. Angew. Chem., Int.
Ed. 2003, 42, 2194.
(9) (a) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Tetrahedron Lett. 2003,
44, 9251. (b) (a) Kim, D.-K.; Chung, W.-J.; Lee, Y.-S. Synlett 2005, 279.
(10) Barton, D.; Godfrey, C.; Morzycki, J.; Motherwell, W. J. Chem.
Soc., Perkin Trans. 1 1982, 1947.
(8) Zhdankin, V. V.; Litvinov, D. N.; Koposov, A. Y.; Luu, T.;
Ferguson, M. J.; McDonald, R.; Tykwinski, R. R. Chem. Commun. 2004,
06.
1
J. Org. Chem, Vol. 70, No. 16, 2005 6485

Zhdankin et al.
of 4c, 4d, and 4e are 2.9, 0.2, and 1.7 M, respectively.
The methyl and ethyl esters 4a and 4b are moderately
soluble in water and acetonitrile but have a low solubility
in dichloromethane (0.003 M for ester 4a). All esters 4
are stable to hydrolysis and can be stored indefinitely
under refrigeration. Treatment of IBX-ester 4c with
trifluoroacetic acid for several hours at room temperature
showed that it is not hydrolyzed to IBX under these
conditions and demonstrated its chemical stability.
In view of the unstable nature of IBX, which was found
to be explode under heating above 200 °C or upon
impact, thermal analyses were preformed on several
IBX ester samples (4a, 4b, and 4c) using traditional
melting points, differential scanning calorimetry (DSC),
and thermal gravimetric analysis (TGA). DCS analysis
for 4a and 4b show broad endotherms centered at 125
and 100 °C, respectively, which correspond to mass losses
of 5.7 and 5.5%, respectively, based on TGA analysis. In
both cases, this is consistent with loss of cocrystallized
solvent from the sample (likely water, based on combus-
tion analysis). Sample 4c shows a much weaker endo-
therm centered at ca. 135 °C, with less than 5% mass
loss over the temperature range up to its decomposition.
At higher temperatures, DSC analyses of 4a and 4b show
exotherms characteristic of decomposition, while 4c
shows endotherm (likely melting point) followed im-
mediately by an exotherm (decomposition). Melting-point
analyses confirm the chemical decomposition of all three
samples into a yellow solid that coats the inner walls of
the melting point tube, empirically suggesting some kind
of decarboxylation process. While no explosive decompo-
sition has been observed for 4a-4c in any of these
experiments, DSC analysis shows that decomposition in
all cases is rapid and exothermic, and TGA confirms
nearly 100% mass loss upon decomposition. As a result,
due caution should be exercised upon heating these
samples at temperatures approaching their decomposi-
tion points.
consisting of two crystallographically independent mol-
ecules. Strong secondary I‚‚‚O bonding interactions be-
tween neighboring molecules affords dimeric pairs. These
dimers are then linked together by a combination of
strong and weak interactions, forming a polymeric motif,
4
much like that observed for IBX in the solid state.
Within each unique molecule of 4c, an intramolecular
close contact between the I(V) center and the oxygen
atom of the ester group (I-O 2.81 and 2.69 Å) affords
the pseudo-benziodoxole ring. X-ray crystallographic
analysis of 4d showed a centrosymmetric arrangement
of four molecules. As observed for 4c, the secondary
I‚‚‚O bonding interactions that link neighboring mol-
ecules are present, as is the intramolecular close contact
between the iodine center and the oxygen atom of the
ester group (I-O 2.68 and 2.67 Å). Whereas crystals of
1
1
3
4c and 4d could be grown from CH CN, the more
sparingly soluble 4a provided X-ray quality crystals only
from DMSO (it should be noted that complex 4a‚DMSO
is considerably more soluble in other solvents than pure
4a). Analysis of the crystals shows a dimeric structure
between two inversion-related molecules. The remaining
close contact to the I(V) center, however, occurs with
oxygen from a DMSO molecule. As found in the struc-
tures of 4c and 4d, the intramolecular I‚‚‚O interaction
involving the iodonium center and ester oxygen is again
significant, with I-O1 ) 2.69 Å.
The intramolecular I‚‚‚O bonding motif with the car-
bonyl oxygen is common to the structures of IBX-esters
4
a, 4c, and 4d‚DMSO and suggests that the presence of
an ester moiety in the ortho position is vital for improved
12,13
solubility.
This results from a disruption of intermo-
lecular I‚‚‚O bonds and a concurrent reduction of the
polymeric interactions found in some iodyl and iodosyl
12
derivatives. In comparison to the IBX-esters, IBX shows
a stronger intramolecular I-O interaction with the
4a
carboxylate oxygen (2.263(2) Å) as well as a three-
dimensional network based on a combination of inter-
molecular O-H‚‚‚O and I‚‚‚O secondary bonding. It is,
therefore, the absence of the hydrogen-bonding interac-
tions in the IBX-esters that appears sufficient to enhance
solubility vs IBX. The consequence of this effect can be
appreciated by considering the structure of 4c, which
shows that, even with partial oligomeric nature on the
basis of I‚‚‚O bonding, considerable solubility can be
maintained.
The composition, structure, and purity of compounds
4
a-j were established through a combination of elemen-
tal analysis, spectroscopic data, electrospray ionization
ESI) mass spectrometry, and single-crystal X-ray analy-
sis. In particular, IR spectra of all compounds show the
(
-1
carbonyl stretch at 1640-1680 cm and an IdO absorp-
-
1
1
tion at 780-740 cm . In the H NMR spectra, a
characteristic pattern of the aromatic protons between
8
.4 and 7.6 ppm and the respective signals of each ester
Preparation and Structure of IBX-Esters Diac-
etates: Pseudocyclic Dess-Martin Periodinane Ana-
logues. To improve the solubility and the potential
reactivity of methyl 2-iodoxybenzoate 4a, it was con-
verted to the acetate (8a) and trifluoroacetate (8b) by
treatment with the corresponding anhydride under reflux
group R are present. The most characteristic signals in
13
C NMR spectra of 4 are those of the ipso carbon, C-IO
2
,
found at ca. 149 ppm.
Single-crystal X-ray analysis of iodoxybenzoate esters
4
a, 4c, and 4d were reported in our preliminary com-
8
munication. The X-ray data revealed the key features
of crystal and molecular structure of IBX-esters and
provided an explanation for the better solubility of
compounds 4c and 4d: a partial disruption of their
polymeric nature due to the redirection of I‚‚‚O secondary
bonding. A broad range of solubility, i.e., 4c vs 4a,
suggested that molecular structure was not the only
factor but that secondary bonding interactions in the solid
state (i.e., polymeric vs nonpolymeric) might also play a
significant role. The structure of 4c showed a unit cell
14
conditions by analogy with the original procedure for
the preparation of DMP (Scheme 2).
(
12) (a) Alcock, N. W.; Sawyer, J. F. J. Chem. Soc., Dalton Trans.
980, 115. (b) Katritzky, A. R.; Savage, G. P.; Palenik, G. J.; Qian, K.;
Zhang, Z.; Durst, H. D. J. Chem. Soc., Perkin Trans. 2 1990, 1657.
c) Naae, D. G.; Gougoutas, J. Z. J. Org. Chem. 1975, 40, 2129.
1
(
(
13) (a) Macikenas, D.; Skrzypczak-Jankun, E.; Protasiewicz, J. D.
Angew. Chem., Int. Ed. 2000, 39, 2007. (b) Macikenas, D.; Skrzypczak-
Jankun, E.; Protasiewicz, J. D. J. Am. Chem. Soc. 1999, 121, 7164.
(
c) Hirt, U. H.; Schuster, M. F. H.; French, A. N.; Wiest, O. G.; Wirth,
T. Eur. J. Org. Chem. 2001, 1569. (d) Hirt, U. H.; Spingler, B.; Wirth,
T. J. J. Org. Chem. 1998, 63, 7674.
(11) Plumb, J. B.; Harper, D. J. Chem. Eng. News 1990, 68, 3.
(14) Dess, D. E.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
6486 J. Org. Chem., Vol. 70, No. 16, 2005

Esters of 2-Iodoxybenzoic Acid
SCHEME 2
Products 8a and 8b precipitated from the reaction
mixture after addition of ether and were isolated by
filtration as white, microcrystalline solids. Bis(trifluoro-
acetate) 8b is highly hygroscopic and should be handled
and stored in dry atmosphere. Both derivatives 8a and
FIGURE 1. (a) Perspective view and selected bond lengths
for molecule 8a. Non-hydrogen atoms are represented by
Gaussian ellipsoids at the 20% probability level, and hydrogen
atoms are shown with arbitrarily small thermal parameters.
15
(
b) Structure and selected bond lengths for DMP analogue 9.
8b gradually lose acetyl moieties on storage producing
Dashed lines I‚‚‚O indicate secondary bonding interactions.
the initial IBX-ester 4a. The structure and composition
of the compounds 8a and 8b were established by elemen-
tal analysis, spectroscopic data, and single-crystal
X-ray analysis for diacetate 8a (Figure 1). In particular,
SCHEME 3
13
C NMR spectra of products 8a and 8b show the signals
of additional carbonyl groups at 172 and 158 ppm,
respectively, and the signals of the ipso carbon, C-I, at
about 150 ppm.
While the solid-state structure of compound 8a is
unique among the known I(V) derivatives that have been
characterized to date (IBX, the IBX esters, and DMP
analogue 9), there are also several similarities. For
example, the geometry around the hypervalent iodine
center retains coordination of the iodine to carbonyl
oxygen O6 (2.6676(17) Å), similar to that found in the
IBX esters. The bonding interactions between iodine
and acetoxy oxygens (O2 and O4), at 2.1249(16) and
compounds 11a and 11b with an acetone solution of
dimethyldioxirane (DDO) afforded the final products 6a
and 6b in high yield (Scheme 3).
Compounds 6a and 6b were isolated in the form of
white, microcrystalline solids, soluble in organic solvents,
including dichloromethane, benzene, and acetone. The
rapid heating and impact tests have corroborated their
nonexplosive nature.
Compounds 6 were analyzed by NMR, IR, spectroscopy,
and ESI-MS. In particular, 13C NMR spectra of each
product 6a and 6b showed a single signal of the carbonyl
carbons at 166.8 and 166.6 ppm, respectively, and the
2
.1088(16) Å, respectively, are similar to that of the
15
alkoxy bond in 9, at 2.296(7) Å. The apical IdO bond
length is also comparable in both cases, at 1.7723(16) Å
and 1.776(9) Å for 8a and 9, respectively. There are,
however, notable differences. The I(V) center of 8a
maintains secondary bonding interactions with both
acetyl carbonyls at 2.8051(17) and 2.7675(17) Å, provid-
ing an unusual heptacoordinate geometry about iodine.
Finally, unlike the polymeric structure of IBX and the
oligomeric nature of the IBX esters and DMP analogue
9
due to intermolecular I‚‚‚O interactions, the coordina-
tion sphere about iodine in 8a is satisfied completely by
intramolecular bonding. As a result, the solubility of 8a
in comparison to IBX and IBX esters is somewhat
increased.
2
signal of the ipso carbon, C-IO , at about 149 ppm. The
1
H NMR spectrum of dimethyl ester 6a showed a single
sharp singlet corresponding to the two identical methoxy
groups. Likewise, the signals corresponding to two iden-
Preparation and Structural Investigation of the
Esters of 2-Iodoxyisophthalic Acid. 2-Iodoxyisoph-
thalate ester 6 can, in principle, provide for the intra-
molecular coordination of the iodine(V) center with two
carbonyl oxygens. It was expected that the additional
coordination could lead to the increased redirection of
secondary bonding from an intermolecular to intra-
molecular mode resulting in improved solubility and
modified reactivity of the reagent. The precursors to the
target structures, 2-iodoisophthalates 11a and 11b, were
prepared from the known 2-iodoisophthaloyl dichloride
1
tical isopropyl groups were present in the H NMR
spectrum of diisopropyl ester 6b at room temperature and
at temperatures as low as -80 °C. The structure of
diisopropyl 2-iodoxyisophthalate 6b in the solid state was
investigated by single-crystal X-ray analysis (Figure 2).
According to the X-ray structural analysis, 6b assumes
a pseudo-centrosymmetric tetramer in the solid state,
composed of four unique molecules linked by secondary
bonding interactions. The IdO bond lengths fall in a very
narrow range of 1.774(4)-1.811(5) Å. The intermolecular
secondary bonding interactions for I(1) and I(2) are
analogous: each establishes two relatively strong I‚‚‚O
bonds with neighboring molecules, with bond lengths in
the range of 2.497(4)-2.692(5) Å. The intermolecular
secondary bonding interactions for I(3) and I(4) are also
analogous: each establishes two somewhat weaker
1
6
1
0, and the corresponding alcohols. The oxidation of
(
15) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
16) (a) Agosta, W. C. Tetrahedron Lett. 1965, 6, 2681. (b) Denmark,
(
S. E.; Stavenger, R. A.; Faucher, A.; Edwards, J. P. J. Org. Chem. 1997,
2, 3375.
6
J. Org. Chem, Vol. 70, No. 16, 2005 6487

Zhdankin et al.
oxidation of benzyl alcohol in the presence of KBr17 in
chloroform at 50 °C cleanly gives benzaldehyde as the
1
only product detected by H NMR spectroscopy (Entry
2
). A variety of secondary alcohols, such as cyclohexanol
and cycloheptanol, are converted to the corresponding
ketones in >90% yields as determined by gas chroma-
tography (GC) analysis (entries 4-7). Furthermore, the
increased solubility of, e.g., 4c, greatly expands the range
of solvents that can be utilized in comparison IBX. The
oxidation of 1-phenylethanol to acetophenone, for ex-
ample, proceeds in good yield (>65%) using CH
CHCl , CH Cl , and benzene.
3
CN,
3
2
2
Methyl 2-[(diacetoxy)iodosyl]benzoate 8a (Entry 10)
and 2-iodoxyisophthalate esters 6 (Entry 11) oxidize
alcohols to the respective aldehydes or ketones in the
presence of trifluoroacetic acid or boron trifluoride ether-
ate. The bis(trifluoroacetate) derivative 8b (Entry 9) can
oxidize alcohols to carbonyl compounds without ad-
ditional acid catalyst. It can be assumed that the more
electrophilic trifluoroacetate species, formed in situ from
4
c or 6 in the presence of trifluoroacetic acid, are the
actual reactive intermediates. As it was shown previ-
ously, the mechanism of oxidation of alcohols with iodine-
FIGURE 2. Perspective view and selected bond lengths for
the four unique molecules in the solid-state tetramer of 6b.
Selected non-hydrogen atoms are represented by Gaussian
ellipsoids at the 20% probability level; the others have been
removed for clarity. Dashed lines I‚‚‚O indicate secondary
bonding interactions.
(
V) reagents includes the initial ligand exchange on the
iodine atom with intermediate formation of alkoxyiodane
species.15 The enhanced electrophilic reactivity of the
iodine(V) center is essential in order to facilitate the
initial interaction of the reagent with the molecule of
alcohol.
I‚‚‚O bonds with neighboring molecules, with bond lengths
in the range of 2.809(4)-3.074(4) Å. Two interesting
observations are seen with respect to the participation
of the various oxygen atoms in these secondary bonds.
First, O(11) and O(21) both form bifurcated bonds with
the I(V) atoms of two neighbors, and one of the two close
contacts in each case is significantly stronger than the
other. Conversely two oxygen atoms, O(31) and O(41),
experience no secondary bonding interactions at all.
Unlike that observed for the structure of 8a, each
unique molecule in the tetramer 6b has only one of the
two carbonyl groups in coordination with the hypervalent
Very recently, we have reported that IBX-esters can
also be used as reagents for the clean and selective
oxidation of organic sulfides to sulfoxides.18 This reaction
does not require acid catalysis, it proceeds without over-
oxidation to sulfones, and it is compatible with the
presence of the hydroxy group, double bond, phenol ether,
benzylic carbon, and various substituted phenyl rings in
the molecule of the substrate. The highly selective
oxidizing reactivity of IBX-esters, combined with their
stability and easiness of preparation, validates potential
importance of these compounds as oxidizing reagents for
organic synthesis.
iodine center, with bond distances ranging from
1
2
.641(5) to 2.710(5) Å. This result contrasts H NMR
spectroscopic analysis of 6b in CD
2
Cl
2
, which showed
Conclusion
equivalent carboxylic groups. This degeneracy was main-
tained down to -80 °C, indicative of a very low energy
barrier for the interconversion process.
Oxidation of Alcohols with IBX-Esters. Oxidation
of the hydroxyl functional group is one of the most
In conclusion, we have reported the preparation and
chemistry of esters of IBX-esters, new pseudobenzio-
doxole-based hypervalent iodine reagents. Various IBX-
esters 4 can be conveniently prepared by the hypochlorite
oxidation of the corresponding 2-iodobenzoate esters and
isolated as chemically stable, microcrystalline products.
Methyl 2-iodoxybenzoate 4a can be further converted to
the diacetate 8a or bis(trifluoroacetate) 8b by the treat-
ment with acetic anhydride or trifluoroacetic anhydride,
respectively. X-ray diffraction analysis of the diacetate
derivative 8a reveals a pseudobenziodoxole structure
with a relatively weak intramolecular I‚‚‚O interaction.
The methyl and isopropyl esters of 2-iodoxyisophthalic
acid (6a,b) were prepared by oxidation of the respective
iodoarenes with dimethyldioxirane. Single-crystal X-ray
diffraction analysis of diisopropyl 2-iodoxyisophthalate
showed intramolecular I‚‚‚O interaction with only one
important transformations in organic synthesis. Accord-
1
ing to literature data, iodylbenzene (PhIO
2
) as well as
other noncyclic iodylarenes are not effective oxidants
toward alcohols, due in part to their polymeric nature
and, as a consequence, decreased solubility. In contrast
to the noncyclic iodylarenes and in agreement with their
structural features, the oxidizing reactivity of IBX-esters
4
is closer to the benziodoxole-based pentavalent iodine
reagents such as IBX.
The isopropyl ester of 2-iodylbenzoic acid 4c is the most
readily available of the new IBX-esters, and it was
therefore chosen to explore the synthetic potential of
these oxidants. A range of alcohols could be oxidized to
the respective carbonyl compounds by reagent 4c under
mild conditions in the presence of trifluoroacetic acid,
(
17) Tohma, H.; Takizawa, S.; Maegawa, T.; Kita, Y. Angew. Chem.,
Int. Ed. 2000, 39, 1306.
BF
3
‚Et
2
O, or KBr as a catalyst (Table 1). For example,
(18) Koposov, A. Y.; Zhdankin, V. V. Synthesis 2005, 22.
6488 J. Org. Chem., Vol. 70, No. 16, 2005

Esters of 2-Iodoxybenzoic Acid
TABLE 1. Oxidation of Alcohols to Carbonyl Compounds with IBX-Esters
reagenta
alcohol
catalyst
reaction time (h)
temperature (°C)
yield (%)
b
entry
1
2
3
4
5
6
7
8
9
4c
4c
4c
4c
4c
4c
4c
4c
8b
8a
6b
benzyl alcohol
benzyl alcohol
benzyl alcohol
cyclohexanol
cyclohexanol
cycloheptanol
cyclooctanol
TFA
1
4
0.5
11
2
2
2
40
50
20
20
40
40
40
20
20
40
40
100c
d
KBr
100
d
BF3‚Et2O
TFA
100
c
95
c
TFA
95
c
TFA
90
c
TFA
95
95
c
cyclooctanol
BF3‚Et2O
none
0.5
0.5
1
d
benzyl alcohol
benzyl alcohol
benzyl alcohol
100
d
1
1
0
1
TFA
TFA
100
d
2
100
a
b
All reactions were performed in dichloromethane using 1 equiv IBX-ester. The respective carbonyl compound and the respective
1
c
aryliodide were the only products determined by GC or H NMR spectroscopic analysis of the reaction mixture. Determined by GC
analysis. d Determined by H NMR spectroscopy.
1
carbonyl oxygen of the two carboxylic groups, while NMR
spectra in solution indicated equivalency of both ester
groups. IBX-esters, methyl 2-[(diacetoxy)iodosyl]ben-
zoate, and 2-iodoxyisophthalate esters can oxidize alco-
hols to the respective aldehydes or ketones in the
presence of trifluoroacetic acid or boron trifluoride ether-
ate. The bis(trifluoroacetate) derivative can oxidize al-
cohols to carbonyl compounds without additional acid
catalyst.
130.6, 127.8, 126.1, 122.1, 119.2, 58.9, 10.0. Anal. Calcd for
C
9
H
9
IO
4
‚H
2
O: C, 33.15; H, 3.40; I, 38.92. Found: C, 33.11; H,
3.41; I, 39.08.
tert-Butyl 2-Iodoxybenzoate 4d. Oxidation of tert-butyl
-iodobenzoate 7d according to general procedure afforded
.99 g (59%) of product 4d, mp 160-162 °C (decomposition;
2
0
recrystallized from CH
2
Cl
2 2 2
/hexanes). Solubility in CH Cl :
5
3
.17 g in 100 g of solvent (up to 0.2 M solutions). IR (KBr):
1
3
057, 2910, 2852, 1672, 1251, 771, 745. H NMR (CDCl ):
δ 8.43 (d, J ) 7.2 Hz, 1H), 8.01 (d, J ) 7.3 Hz, 1H), 7.93 (t,
J ) 7.8 Hz, 1H), 7.67 (t, J ) 8.0 Hz, 1H), 1.62 (s, 9H).
1
3
C NMR (CDCl
27.8, 85.9, 28.1. Anal. Calcd for C11
I, 37.76. Found: C, 39.39; H, 4.03; I, 37.28.
3
): δ 167.2, 147.8, 140.9, 131.9, 130.4, 128.0,
Experimental Section
1
H13IO
4
: C, 39.31; H, 3.90;
For general experimental methods and synthesis of starting
esters 7a-j, see the Supporting Information.
(
-)-Menthyl 2-Iodoxybenzoate 4e. Oxidation of (-)-
General Procedure for Oxidation of 2-Iodobenzoate
Esters. Dichloromethane (20 mL) was added to a vigorously
stirred suspension of the appropriate ester of 2-iodobenzoic
acid 7 (5 mmol) and sodium hypochlorite solution (“bleach”,
menthyl 2-iodobenzoate 7e according to general procedure
afforded 1.50 g (69%) of product 4e, mp 101 °C (decomposition;
recrystallized from EtOAc/hexanes); [R]
20
D
) -63°. Solubility
in CH
IR (KBr): 1679, 774, 746 cm
d, J ) 7.8 Hz, 1H), 8.06 (d, J ) 7.4, 1H), 7.91 (t, J ) 7.6 Hz,
2 2
Cl : 54.11 g in 100 g of solvent (up to 1.71 M solutions).
5% NaOCl, 15 mL), and then acetic acid (5 mL) was added
-1
1
.
3
H NMR (CDCl ): δ 8.44
dropwise in 10 min at room temperature. The resulting
mixture was stirred overnight. The initially formed yellow
mixture turned into a white precipitate (4a and 4b) or a
colorless solution (4d-4j). Products 4a and 4b were isolated
by filtration in analytically pure form as white, microcrystal-
line solids. Esters 4d-j were extracted from the reaction
mixture with dichloromethane (5 × 10 mL). The extract was
(
1
4
2
6
1
2
1 2
H), 7.67 (t, J ) 7.5 Hz, 1H), 5.01 (td, J ) 11.0 Hz, J )
.0 Hz, 1H), 2.18 (d, J ) 11 Hz, 1H), 1.88 (m, 1H), 1.75 (m,
H), 1.58 (m, 2H), 1.11 (m, 3H), 0.92 (m, 6H), 0.75 (d, J )
13
.8 Hz, 3H). C NMR (CDCl
3
): δ 167.6, 148.6, 135.0, 132.4,
30.3, 126.9, 125.1, 78.7, 47.1, 40.5, 34.1, 31.4, 26.4, 23.5, 21.9,
4 2
0.7, 16.5. Anal. Calcd for C17H23IO ‚H O: C, 46.80; H, 5.78.
3
washed with a saturated aqueous solution of NaHCO , dried
Found: C, 47.14; H, 5.47. ES MS: m/ z (%) 859 (100, [2M +
with MgSO
4
, and evaporated in a vacuum to afford crude
+
Na] ).
products as colorless or pale-yellow amorphous solids or oils.
(
+)-Menthyl 2-Iodoxybenzoate 4f. Oxidation of (+)-
2 2
Crystallization of crude products from acetonitrile or CH Cl /
menthyl 2-iodobenzoate 7f according to general procedure
afforded 1.37 g (63%) of product 4f, mp 100-102 °C (decom-
hexanes furnished analytically pure products 4d-j in white,
microcrystalline form, which, however, could be converted back
2
0
position; recrystallized from EtOAc/hexanes); [R]
D
) +62°.
): δ 8.41 (d,
J ) 7.6 Hz, 1H), 8.05 (d, J ) 6.8 Hz, 1H), 7.90 (t, J ) 7.3 Hz,
into the amorphous form by dissolving the crystals in CH
followed by solvent evaporation.
2 2
Cl
-
1 1
IR (KBr): 1675, 773, 742 cm . H NMR (CDCl
3
Methyl 2-Iodoxybenzoate 4a. Oxidation of methyl 2-iodo-
benzoate 7a according to general procedure afforded 0.33 g
1
H), 7.64 (t, J ) 7.4 Hz, 1H), 4.97 (td, J
1 2
) 10.7 Hz, J )
4
.4 Hz, 1H), 2.17 (m, 1H), 1.87 (m, 1H), 1.75 (m, 2H), 1.57
(
21%) of product 4a, mp 194-196 °C (decomposition). The
(
m, 2H), 1.10 (m, 3H), 0.91 (m, 6H), 0.72 (d, J ) 6.8 Hz, 3H).
3
lower preparative yield for this product is explained by its high
1
-
1
C NMR (CDCl
125.1, 78.5, 47.0, 40.3, 33.9, 31.2, 26.4, 23.4, 21.9, 20.7, 16.5.
Anal. Calcd for C17 ‚H O: C, 46.80; H, 5.78. Found: C,
3
): δ 167.6, 148.6, 134.9, 132.3, 130.2, 126.9,
solubility in water. IR (KBr): 3063, 1687, 786, 755 cm
.
1
H NMR (DMSO-d
.10 (dd, J ) 7.5 Hz, J
) 1.2 Hz, 1H), 7.76 (td, J
6
): 8.28 (dd, J
) 1.2 Hz, 1H), 8.04 (td, J
) 7.2 Hz, J ) 1.2 Hz, 1H), 4.00
): δ 167.2, 150.6, 134.6, 131.7,
IO O: C,
1
) 7.7 Hz, J
2
) 0.9 Hz, 1H),
H
23IO
4
2
8
1
2
1
) 7.5 Hz,
+
4
7.11; H, 5.45. ES MS: m/ z (%) 859 (100, [2M + Na] ), 419
J
2
1
2
+
1
3
(15, [M + H] ).
(
s, 3H). C NMR (DMSO-d
6
1
29.9, 125.7, 123.0, 53.6. Anal. Calcd for C
8
H
7
4
‚H
2
(()-Menthyl 2-Iodoxybenzoate 4g. Oxidation of (()-
menthyl 2-iodobenzoate 7g according to general procedure
afforded 1.59 g (73%) of product 4g, mp 99-100 °C (decom-
position; recrystallized from MeCN/hexanes). IR (KBr): 1679,
3
0.79; H, 2.91; I, 40.67. Found: C, 30.81; H, 2.92; I, 40.42.
Ethyl 2-Iodoxybenzoate 4b. Oxidation of ethyl 2-iodo-
benzoate 7b according to general procedure afforded 0.99 g
-
1
1
(
61%) of product 4b, mp 196-198 °C (decomposition; recrystal-
3
774, 746 cm . H NMR (CDCl ): 8.47 (d, J ) 7.6 Hz, 1H),
-
1
lized from acetonitrile). IR (KBr): 1633, 804, 732 cm
.
8.03 (d, J ) 7.3 Hz, 1H), 7.91 (t, J ) 7.3 Hz, 1H), 7.63 (t, J )
7.3 Hz, 1H), 4.91 (m, 1H), 2.11 (m, 1H), 1.82 (m, 1H), 1.73 (m,
2H), 1.55 (m, 2H), 1.07 (m, 3H), 0.91 (m, 6H), 0.68 (d, J )
1
H NMR (DMSO-d
) 7.4 Hz, J
.2 Hz, 1H), 7.77 (t, J ) 7.6 Hz, 1H), 4.45 (q, J ) 7.1 Hz, 2H),
.38 (t, J ) 7.1 Hz, 3H). 13C NMR (DMSO-d
): δ 162.8, 146.6,
6
): δ 8.27 (d, J ) 7.7 Hz, 1H), 8.10 (dd,
) 1.2 Hz, 1H), 8.04 (td, J ) 7.6 Hz, J )
2 1 2
J
1
1
1
1
3
3
6.6 Hz, 3H). C NMR (CDCl ): 167.7, 148.9, 135.1, 132.2,
6
130.3, 127.0, 125.2, 78.6, 47.1, 40.5, 34.1, 31.6, 26.4, 23.5, 22.0,
J. Org. Chem, Vol. 70, No. 16, 2005 6489

Zhdankin et al.
1H), 4.00 (s, 3H), 1.90 (s, 6H). 13C NMR (DMSO-d
): δ 172.1,
6
167.4, 150.7, 134.8, 131.9, 130.2, 125.9, 123.3, 53.8, 21.1.
Crystal Data for 8a. X-ray intensity data were collected
at -80 °C on a Bruker PLATFORM/SMART 1000 charge-
coupled device (CCD) diffractometer with Mo KR radiation
2
0.8, 16.6. Anal. Calcd for C17
Found: C, 48.71; H, 5.68.
(1S)-endo]-(-)-Bornyl 2-Iodoxybenzoate 4h. Oxidation
H
23IO
4
:
C, 48.82; H, 5.54.
[
of [(1S)-endo]-(-)-bornyl 2-iodobenzoate 7h according to gen-
eral procedure afforded 1.31 g (63%) of product 4h, mp 164-
(
λ ) 0.71073 Å) using a crystal with dimensions of 0.83 ×
1
(
(
65 °C (decomposition; recrystallized from MeCN/hexanes). IR
3
KBr): 3057, 2882, 1678, 1296, 775, 750 cm-1
CDCl ): δ 8.41 (d, J ) 7.2 Hz, 1H), 8.05 (d, J ) 7.6 Hz, 1H),
.87 (t, J ) 7.4 Hz, 1H), 7.61 (t, J ) 7.2 Hz, 1H), 5.11 (m, 1H),
.46 (m, 1H), 2.03 (m, 1H), 1.77 (m, 2H), 1.40 (m, 1H), 1.26
.
1
H NMR
0.30 × 0.22 mm. C H IO , FW ) 396.12 g/mol , triclinic space
12 13
7
group ) Ph 1 (No. 2), unit cell dimensions a ) 8.0018(3) Å,
3
b ) 8.7268(4) Å, c ) 11.8450(5) Å, R ) 91.4834(7)°, â )
7
2
3
1
07.9121(7)°, γ ) 114.6969(7)°, V ) 703.56(5) Å , Z ) 2, Fcalcd
3
-3
)
1.870 g/cm , µ ) 2.304 mm , 2θ max ) 52.74°, R
1
(F) )
(
m, 1H), 1.14 (m, 1H), 0.95 (s, 3H), 0.91 (s, 3H), 0.87 (s, 3H).
2
2
2
13
0.0181 for 2805 reflections with F g 2σ(F ), wR (F ) ) 0.0481
C NMR (CDCl
25.0, 83.8, 49.2, 47.9, 44.8, 36.6, 27.9, 27.7, 19.6, 18.9, 13.7.
Anal. Calcd for C17 : C, 49.05; H, 5.09; I, 30.49. Found:
C, 48.94; H, 5.26; I, 29.90.
-Adamantyl 2-Iodoxybenzoate 4i. Oxidation of 2-ada-
3
): δ 168.3, 149.4, 134.9, 131.9, 130.1, 126.8,
0
0
2
2
2
for 2830 independent reflections (F
0
g -3σ(F
g EnDash3σ(F )), CCDC
0
)) and 184
o
1
2
2
2
parameters, GOF(F ) ) 1.099 (F
0
H
21IO
4
2
60006. For further details on crystal structure of 8a see the
Crystallographic Information File (deposited as Supporting
2
Information).
mantyl 2-iodobenzoate 7i according to general procedure
afforded 1.72 g (83%) of product 4i, mp 138-140 °C (decom-
position; recrystallized from CH Cl /hexanes). IR (KBr): 3061,
2 2
Methyl 2-[(Bistrifluoroacetoxy)iodosyl]benzoate 8b.
Reaction of methyl ester of IBX 4a with trifluoroacetic
anhydride according to the general procedure afforded 55% of
extremely hygroscopic product 8b, mp 143-145 °C. IR
-
1
1
2
854, 1670, 1289, 763, 752 cm . H NMR (CDCl
3
): δ 8.46
(
d, J ) 7.8 Hz, 1H), 8.13 (d, J ) 7.5 Hz, 1H), 7.94 (t, J )
(
NaCl): 3065, 2968, 1786, 1669, 1338, 1308, 1162, 852, 781,
7
4
.5 Hz, 1H), 7.69 (t, J ) 7.5 Hz, 1H), 5.30 (m, 1H), 2.10 (m,
13
-
1
1
750, 730 cm . H NMR (DMSO-d
6
): δ 8.31 (d, J ) 7.8 Hz,
H), 8.10 (m, 2H), 7.80 (t, J ) 7.5 Hz, 1H), 4.01 (s, 3H).
3
H), 1.96 (m, 6H), 1.79 (m, 2H), 1.64 (m, 2H). C NMR
): δ 167.6, 148.1, 135.2, 132.4, 130.4, 127.0, 124.8, 81.3,
7.1, 36.3, 31.8, 27.1, 26.8. Anal. Calcd for C17 : C, 49.29;
1
(CDCl
3
1
6
C NMR (DMSO-d ): δ 167.7, 158.4 (q, J ) 38.5 Hz), 150.1,
3
H19IO
4
1
35.1, 132.3, 130.4, 125.7, 123.3, 115.3 (q, J ) 289 Hz), 54.1.
H, 4.62. Found: C, 49.19; H, 4.71.
Anal. Calcd for C12
7 6 7
H F IO : C, 28.59; H, 1.40. Found: C, 28.33;
1
-Adamantyl 2-Iodoxybenzoate 4j. Oxidation of 1-ada-
H, 1.76.
mantyl 2-iodobenzoate 7j according to general procedure
afforded 1.37 g (66%) of product 4j, mp 120-121 °C (decom-
position; recrystallized from CH Cl /hexanes). IR (KBr): 3061,
2 2
General Procedure for the Preparation of Esters of
-Iodoisophthalic Acid 11a,b. 2-Iodobenzene-1,3-benzene-
2
dicarbonyl dichloride 10 (3.29 g, 10 mmol) was placed into a
round-bottom flask. Appropriate alcohol (50 mL) was added
into the flask, and mixture was refluxed for 2 h. Then the
excess of alcohol was evaporated, and the mixture was
separated by column chromatography (ethyl acetate/hexanes
-
1
1
2
855, 1670, 1290, 763, 752 cm . H NMR (CDCl
3
): δ 8.45
(
d, J ) 7.2 Hz, 1H), 8.01 (d, J ) 7.7 Hz, 1H), 7.88 (t, J )
7
3
1
.2 Hz, 1H), 7.62 (t, J ) 7.4 Hz, 1H), 2.25 (m, 6H), 2.01 (m,
13
H), 1.72 (m, 6H). C NMR (CDCl
32.2, 130.5, 128.1, 124.7, 85.3, 41.3, 35.9, 31.0. Anal. Calcd
: C, 49.29; H, 4.62; I, 30.64. Found: C, 49.75; H,
.77; I, 29.09.
3
): δ 166.8, 148.1, 134.6,
1
:2) to afford analytically pure esters 11.
Dimethyl 2-Iodoisophthalate 11a. Reaction of methanol
for C17H19IO
4
4
with 2-iodobenzene-1,3-benzenedicarbonyl dichloride 10 ac-
cording to general procedure afforded 2.85 g (89%) of product
Alternative Procedure for Hypochlorite Oxidation.
Isopropyl 2-Iodoxybenzoate 4c. To a rigorously stirred
suspension of isopropyl ester of 2-iodobenzoic acid (1.45 g,
19
1
2
1a, mp 49-50 °C (literature value ) 49-50 °C). IR (KBr):
1
-1
949, 1731, 1434, 1253, 995 cm . H NMR (CDCl
3
): δ 7.63
) 8.3 Hz, J
3
): δ 168.2, 139.8,
5
mmol) and sodium hypochlorite solution (“bleach”, 5%
(
dd, J
1
) 7.8 Hz, J
2
) 0.7 Hz, 2H), 7.45 (dd, J
1
2
)
NaOCl, 15 mL), 20 mL of dichloromethane was added and then
excess dry ice over the course of 10 min. The reaction mixture
was stirred overnight, the organic layer separated, and the
aqueous layer extracted three times with dichloromethane
7.1 Hz, 1H), 3.96 (s, 6H). 13
131.5, 128.1, 91.9, 53.0.
C NMR (CDCl
Diisopropyl 2-Iodoisophthalate 11b. Reaction of 2-pro-
panol with 2-iodobenzene-1,3-benzenedicarbonyl dichloride 10
according to general procedure afforded 3.05 g (81%) of product
(
3 × 10 mL). The combined organic fractions were dried over
anhydrous magnesium sulfate, and the solvent was evaporated
1
9
1
1b, mp 37-38 °C. IR (KBr): 2982, 1724, 1453, 1279, 1105,
in a vacuum to afford 1.43 g (89%) of product 4c, mp 156-
1
(
-1
1
38 cm . H NMR (CDCl
3
): δ 7.55 (dd, J
) 8.3 Hz, J ) 6.8 Hz, 1H), 5.3
): δ 167.5,
40.4, 130.9, 128.0, 91.3, 70.1, 21.9. Anal. Calcd for
: C, 44.70; H, 4.55. Found: C, 44.88; H, 4.60.
Preparation of Dimethyl 2-Iodoxyisophthalate 6a.
1 2
) 8.3 Hz, J )
57 °C (decomposition; recrystallized from CH
2
Cl
): δ 8.34 (d, J )
.8 Hz, 1H), 8.01 (d, J ) 7.6 Hz, 1H), 7.84 (t, J ) 7.5 Hz, 1H),
.58 (t, J ) 7.4 Hz, 1H), 5.31 (m, 1H) 1.35 (d, J ) 6.2 Hz, 6H).
2
/ether). IR
.0 Hz, 2H), 7.42 (dd, J
1
2
-
1 1
KBr): 1673, 789, 743 cm . H NMR (CDCl
3
13
(
m, 2H), 1.40 (d, J ) 6.1 Hz, 12H). C NMR (CDCl
3
7
7
1
14 4
C H17IO
13
C NMR (CDCl
3
): δ 167.5, 149.6, 134.9, 131.8, 130.2, 126.8,
1
24.8, 71.9, 21.8. Anal. Calcd for C10H11IO : C, 37.29; H, 3.44;
4
Freshly prepared dioxirane (30 mL, 0.1 M) was added to the
stirred mixture ester 11a (1 mmol) in 5 mL of methylene
chloride at 0 °C. The reaction mixture was stirred at room
temperature for additional 8 h. The resulting white precipitate
was filtered and washed with diethyl ether and dried in a
vacuum to afford 266 mg (76%) of analytically pure 6a, mp
140-141 °C (with decomposition). IR (KBr): 2956, 1712, 1686,
I, 39.40. Found: C, 37.21; H, 3.49; I, 39.36.
General Procedure for the Preparation of the Diac-
etates 8a,b. Methyl ester of IBX 4a (2.9 g, 10 mmol) and the
appropriate anhydride (20 mL) were placed into a round-
bottom flask, and the mixture was stirred for 2 h under reflux.
After the solution cooled, 50 mL of dry ether was added into
the flask and the white precipitate immediately formed. The
product was filtered through the filter funnel under argon and
dried in vacuo.
-
1
1
1437, 1303, 1279, 992, 828, 749 cm
.
H NMR (CDCl
) 7.7 Hz,
): δ 166.8,
49.4, 133.0, 131.1, 130.9, 52.9. Anal. Calcd for C10 IO : C,
3
/
DMSO-d ): δ 8.01 (d, J ) 7.3 Hz, 2H), 7.73 (td, J
6
1
1
3
J
2
) 0.7 Hz, 1H), 3.99 (s, 6H). C NMR (CDCl
3
1
3
H
9
6
Methyl 2-[(Diacetoxy)iodosyl]benzoate 8a. Reaction of
compound 4a with acetic anhydride according to the general
procedure afforded 2.81 g (71%) of white hygroscopic product
4.11; H, 2.58; I, 36.04. Found: C, 34.26; H, 2.53; I, 35.76.
ESI HRMS: m/z (%) 374.9336 (100%, [M + Na] ).
+
Preparation of Diisopropyl 2-Iodoxyisophthalate 6b.
Freshly prepared dioxirane (30 mL, 0.1 M) was added to the
8
a, mp 150-151 °C (in sealed capillary; with decomposition).
-1
IR (NaCl): 3057, 2956, 1659, 1330, 1275, 1256, 833, 748 cm
.
1
H NMR (DMSO-d
6
): δ 8.28 (dd, J
) 7.8 Hz, J ) 1.2 Hz, 1H), 8.05 (td J
) 1.5 Hz, 1H), 7.76 (td, J ) 7.6 Hz, J ) 1.2 Hz,
1 2
) 7.8 Hz, J ) 1.0 Hz,
1
7
H), 8.09 (dd, J
.6 Hz, J
1
2
1
)
(
19) Whitmore, F. C.; Perkins, R. P. J. Am. Chem. Soc. 1929, 51,
2
1
2
3352.
6490 J. Org. Chem., Vol. 70, No. 16, 2005

Esters of 2-Iodoxybenzoic Acid
stirred mixture ester 11b (1 mmol) in 5 mL of methylene
chloride at 0 °C. The reaction mixture was stirred at room
temperature for additional 8 h, then the solvent was evapo-
rated, and the white solid residue was recrystallized with
methylene chloride/diethyl ether and dried in a vacuum to
afford 370 mg (91%) of analytically pure product 6b, mp 136-
General Procedure for Oxidation of Alcohols with
Ester 4c. A solution of the appropriate alcohol (0.5 mmol) in
methylene chloride (2 mL) was added to a solution of IBX-
ester 4c (0.161 g, 0.5 mmol) in methylene chloride (5 mL).
3 2
Trifluoroacetic acid (0.06 g, 0.5 mmol) (or BF ‚Et O, 0.07 g,
0.5 mmol) in entries 3 and 8) was then added dropwise to this
mixture. The reaction mixture was stirred at 40 °C for 2 h (or
as specified in the Table 1). A portion of the crude reaction
mixture (1.5 mL) was passed through 1 cm of silica gel
1
1
2
6
1
37 °C (with decomposition). IR (KBr): 2980, 1714, 1659, 1283,
-
1 1
103, 911, 751 cm . H NMR (CDCl
3
): δ 7.88 (d, J ) 7.6 Hz,
H), 7.57 (t, J ) 7.5 Hz, 1H), 5.31 (m, 2H), 1.43 (d, J )
1
3
.1 Hz, 12H). C NMR (CDCl
3
δ 166.6, 149.3, 133.7, 132.4,
: C, 41.19; H, 4.20;
2 2
suspended in a Pasteur pipet and eluted with CH Cl
31.9, 72.1, 22.0. Anal. Calcd for C14
H
17IO
6
(2-3 mL) and then diluted to 10 mL and analyzed by GC mass
I, 31.09. Found: C, 40.96; H, 4.13; I, 30.90. ESI HRMS: m/z
spectroscopy.
+
(
%) 430.9962 (100%, [M + Na] ).
Crystal Data for 6b. X-ray intensity data were collected
Acknowledgment. This work was supported by a
research grant from the National Science Foundation
(CHE-0353541), NSF-MRI Award CHE-0416157, NIH
Grant R15 GM065148-01, the Natural Sciences and
Engineering Research Council of Canada, and the
University of Alberta.
at -80 °C on a Bruker PLATFORM/SMART 1000 CCD
diffractometer with Mo KR radiation (λ ) 0.71073 Å) using a
3
crystal with dimensions of 0.22 × 0.22 × 0.05 mm . C56
H
68
I
4
O
24
,
3
FW ) 1632.70 g/mol , orthorhombic space group ) Pna2
1
(
No. 33), unit cell dimensions a ) 19.7076(11) Å, b )
3
1
4.2272(8) Å, c ) 23.5360(13) Å, V ) 6599.1(6) Å , Z ) 4, Fcalcd
3
-3
)
1.643 g/cm , µ ) 1.963 mm , 2θ max ) 52.76°, R
1
(F) )
2
2
2
0
.0399 for 2805 reflections with F
0
g 2σ(F
0
), wR
g -3σ(F
0
g EnDash3σ(F )), CCDC
2
(F ) ) 0.0811
Supporting Information Available: Details of experi-
mental procedures, spectroscopic data of the reaction products,
and X-ray structures of 6b and 8a in CIF format. This material
is available free of charge via the Internet at http://pubs.acs.org.
2
2
for 12996 independent reflections (F
0
0
)) and 774
2
2
2
parameters, GOF(F ) ) 1.013 (F
2
0
70007. For further details on crystal structure of 6b see the
Crystallographic Information File (deposited as Supporting
Information).
JO051010R
J. Org. Chem, Vol. 70, No. 16, 2005 6491