2-Iodylphenol ethers: Preparation, X-ray crystal structure, and reactivity of new hypervalent iodine(V) oxidizing reagents

Article abstract of DOI:10.1021/jo0614947

2-Iodylphenol ethers were prepared by the dimethyldioxirane oxidation of the corresponding 2-iodophenol ethers and isolated as chemically stable, microcrystalline products. Single-crystal X-ray diffraction analysis of 1-iodyl-2-isopropoxybenzene 8c and 1-iodyl-2-butoxybenzene 8d revealed pseudopolymeric arrangements in the solid state formed by intermolecular interactions between IO₂ groups of different molecules. 2-Iodylphenol ethers can selectively oxidize sulfides to sulfoxides and alcohols to the respective aldehydes or ketones.

Full text of DOI:10.1021/jo0614947

2-Iodylphenol Ethers: Preparation, X-ray Crystal Structure, and
Reactivity of New Hypervalent Iodine(V) Oxidizing Reagents
Alexey Y. Koposov, Rashad R. Karimov, Ivan M. Geraskin, Victor N. Nemykin,* and
Viktor V. Zhdankin*
Department of Chemistry and Biochemistry, UniVersity of MinnesotasDuluth, Duluth, Minnesota 55812
Vzhdanki@d.umn.edu; Vnemykin@d.umn.edu
ReceiVed July 18, 2006
2-Iodylphenol ethers were prepared by the dimethyldioxirane oxidation of the corresponding 2-iodophenol
ethers and isolated as chemically stable, microcrystalline products. Single-crystal X-ray diffraction analysis
of 1-iodyl-2-isopropoxybenzene 8c and 1-iodyl-2-butoxybenzene 8d revealed pseudopolymeric arrange-
ments in the solid state formed by intermolecular interactions between IO2 groups of different molecules.
2-Iodylphenol ethers can selectively oxidize sulfides to sulfoxides and alcohols to the respective aldehydes
or ketones.
Introduction
as mild and highly selective reagents for the oxidation of
alcohols to carbonyl compounds as well as for a variety of other
synthetically useful oxidative transformations.2a,b However, the
explosive character and low solubility of IBX in common
organic solvents except DMSO, combined with the susceptibility
of DMP to moisture and prolonged storage,2c restrict practical
application of these reagents.
The low solubility of IBX 1 arises from strong intermolecular
secondary I‚‚‚O contacts, hydrogen bonding, and π-stacking
observed for IBX in solid state.3 Several research groups have
tried to overcome this preparative limitation by performing
oxidation at elevated temperatures,4a using an ionic liquid and
water as a reaction medium,4b or functionalizing IBX aromatic
core.4c Also, several solid-supported reagents in which the IBX
scaffold is linked to a polymer have been reported.5 Another
Oxidizing reagents are essential components of the modern
organic synthetic methodology. The selective oxidation of
alcohols to the corresponding carbonyl compounds, as well as
selective oxidation of sulfides to sulfoxides and other oxidative
transformations, often represents the essential steps in the total
synthesis of complex natural products. During the past decade,
hypervalent iodine compounds have attracted significant interest
as mild, selective, and environmentally benign oxidizing
reagents in organic chemistry.1 Particularly usefuls oxidizers
are the pentavalent iodine compounds, namely, 1-hydroxy-(1H)-
benzo-1,2-iodoxol-3-one 1-oxide (2-iodoxybenzoic acid, IBX,
1) and its acetylation product, Dess-Martin periodinane (DMP,
2), which are now employed extensively in organic synthesis
(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. Koser G. F. Aldrichim. Acta 2001, 34, 89. Koser, G. F. AdV.
Heterocycl. Chem. 2004, 86, 225. (c) Moriarty, R. M. J. Org. Chem. 2005,
70, 2893. Moriarty, R. M.; Prakash, O. AdV. Heterocycl. Chem. 1998, 69,
1. Moriarty, R. M.; Prakash, O. Org. React. 1999, 54, 273-418. Moriarty,
R. M.; Prakash, O. Org. React. 2001, 57, 327. (d) Morales-Rojas, H.; Moss,
R. A. Chem. ReV. 2002, 102, 2497. (d) Zhdankin, V. V.; Stang, P. J. Chem.
ReV. 2002, 102, 2523. (e) HyperValent Iodine Chemistry; Wirth, T., Ed.;
Topics in Current Chemistry, Vol. 224, Springer-Verlag: Berlin, Heidelberg,
2003. (f) Ochiai, M. In Chemistry of HyperValent Compounds; Akiba, K.,
Ed.; VCH Publishers: New York, 1999. (g) Tohma, H.; Kita, Y. AdV. Synth.
Catal. 2004, 346, 111. (h) Togo, H.; Sakuratani, K. Synlett 2002, 1966.
(2) (a) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656. (b) Zhdankin,
V. V. Curr. Org. Synth. 2005, 2, 121. (c) Ladziata, U.; Zhdankin, V. V.
ARKIVOC 2006, (ix), 26. (c) Meyer, S. D.; Schreiber, S. L. J. Org. Chem.
1994, 59, 7549.
(3) Stevenson, P. J.; Treacy, A. B.; Nieuwenhuyzen, M. J. Chem. Soc.,
Perkin Trans. 2 1997, 589.
(4) (a) More, J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001. (b) Liu, Z.;
Chen, Z.-C.; Zheng, Q.-G. Org. Lett. 2003, 5, 3321. (c) Thottumkara, A.
P.; Vinod, T. K. Tetrahedron Lett. 2002, 43, 569.
(5) (a) Muelbaier, M.; Giannis, A. Angew. Chem., Int. Ed. 2001, 40,
4393. (b) Sorg, G.; Mengei, A.; Jung, G.; Rademann, J. Angew. Chem.,
Int. Ed. 2001, 40, 4395. (c) Reed, N. N.; Delgado, M.; Hereford, K.;
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10.1021/jo0614947 CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/23/2006
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J. Org. Chem. 2006, 71, 8452-8458

2-Iodylphenol Ethers
fruitful approach initially proposed by Protasiewicz6 consists
of incorporation of an ortho substituent into iodylarene (e.g.,
sulfone), thus resulting in intramolecular secondary bonding.
This ortho stabilization leads to a partial disruption of the
polymeric network and consequently enhances solubility. More
recently, investigations from our group have resulted in a series
of stable and soluble IBX analogues: IBX-amides 3,7a IBX-
esters 4,7b as well as 2-iodylsulfonamides7c and 2-iodylsulfonate
esters.7d According to X-ray data, a planar pseudobenziodoxole
moiety due to the intramolecular nonbonding iodine-oxygen
interaction is a key structural feature present in this series of
compounds.7 Readily available hypervalent iodine reagents 3
and 4 possess reactivity similar to IBX and DMP and proved
to be useful oxidizing reagents toward alcohols7 and sulfides.8
The synthesis of polymer supported IBX esters and amides has
been reported as well.9 Recently, we have reported on the
preparation and oxidative properties of N-(2-iodylphenyl)-
acylamides (NIPA, 5), which are soluble and stable IBX
analogues having a pseudobenziodoxazine structure.10
SCHEME 1
SCHEME 2
Results and Discussion
The starting 2-iodophenol ethers 7b-d were prepared by a
known procedure12 from 2-iodophenol 6 and the respective alkyl
bromides (Scheme 1), while the methyl ether of 2-iodophenol
(7a) was purchased from commercial sources.
Phenol ethers 7a-d were then oxidized with dimethyldiox-
irane to afford 2-iodylphenol ethers 8 in good yields (Scheme
2). Our attempts to use oxidants other than dimethyldioxirane
oxidizers (e.g., sodium hypochlorite or Oxone) for this oxidation
were unsuccessful.
Products 8 were isolated by filtration of the reaction mixture
as white, stable, microcrystalline compounds and were analyzed
by NMR spectroscopy, elemental analysis, high-resolution mass
spectrometry, and for compounds 8c and 8d, by X-ray crystal-
lography. In particular, 13C NMR spectra of products 8 showed
the signals of the ipso carbon, C-I, at about 138 ppm, as well
as signals corresponding to the carbon in the ortho position,
C-O, at about 156 ppm. Compounds 8b and 8d were found to
be soluble in various solvents, while products 8a and 8c
appeared to be almost insoluble in any nonpolar organic
solvents. It should be noted that compared to IBX all compounds
8 are nonexplosive at the temperatures close to their melting
point.
Molecular structures of compounds 8c and 8d have been
determined by single-crystal X-ray crystallography. The CAM-
ERON diagrams of 8c and 8d are presented in Figures 1 and 2,
while selected metric parameters are listed in Table 1. Both
structures revealed a pseudo-cyclic four-membered ring motif
formed by close contact (2.881-2.930 Å) between the hyper-
valent iodine center and the phenolic oxygen atom, which is
smaller than sum of van der Waals radii of iodine and oxygen
atoms (Figures 1 and 2).
The crystal packing in compounds 8c and 8d is shown in
Figures 3 and 4. Examination of these data provides, in
particular, a possible explanation of the observed significant
difference in solubilities of these two compounds (product 8d
is soluble in various solvents, while 8c is almost insoluble in
any nonpolar organic solvents).
The crystal structure in both cases reveals polymeric-chain
arrangements in the solid state formed by the strong intermo-
lecular interactions between IO2 groups of neighboring mol-
To further explore the effects of ortho substituents, we
considered the development and investigation of iodylarenes
based on the readily available ethers of 2-iodophenol. Two
examples of these compounds, the methyl and ethyl ethers of
2-iodylphenol, were previously reported more than 40 years
ago.11 In these old publications,11 however, the structure and
chemical reactivity of these compounds were not described.
Here, we present the synthesis and X-ray structural study of a
series of new 2-iodylphenol ethers (8, see Scheme 2) and
demonstrate that these compounds are potent oxidizing reagents
toward alcohols and organic sulfides.
(6) Macikenas, D.; Skrzypczak-Jankun, E.; Protasiewicz, J. D. Angew.
Chem., Int. Ed. 2000, 39, 2007.
(7) (a) 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. (b) Zhdankin, V. V.; Litvinov, D. N.; Koposov, A. Y.;
Ferguson, M. J.; McDonald, R.; Tykwinski, R. R. J. Chem. Soc., Chem.
Commun. 2004, 106. Zhdankin, V. V.; Koposov, A. Y.; Litvinov, D. N.;
Ferguson, M. J.; McDonald, R.; Luu, T.; Tykwinski, R. R. J. Org. Chem.
2005, 70, 6484. (c) Koposov, A. Y.; Litvinov, D. N.; Zhdankin, V. V.
Tetrahedron Lett. 2004, 45, 2719; Koposov, A. Y.; Nemykin, V. N.;
Zhdankin, V. V. New J. Chem. 2005, 29, 998. (d) Zhdankin, V. V.;
Goncharenko, R. N.; Litvinov, D. N.; Koposov, A. Y. ARKIVOC 2005,
(iV), 8.
(8) Koposov, A. Y.; Zhdankin, V. V. Synthesis 2005, 22.
(9) (a) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Tetrahedron Lett. 2003,
44, 9251. (b) Kim, D.-K.; Chung, W.-J.; Lee, Y.-S. Synlett 2005, 279.
(10) (a) Ladziata, U.; Koposov, A. Y.; Lo, K. Y.; Willging, J.; Nemykin,
V. N.; Zhdankin, V. V. Angew. Chem., Int. Ed. 2005, 44, 7127. (b) Ladziata,
U.; Willging, J.; Zhdankin, V. V. Org. Lett. 2006, 8, 167.
(11) (a) Gakovic, Z.; Morgan, K. J. J. Chem. Soc. B: Phys. Org. 1967,
5, 416. (b) Sharefkin, J. G.; Saltzman, H. Anal. Chem. 1963, 35, 1428. (c)
Bell, R.; Morgan, K. J. J. Chem. Soc., Abstr. 1960, 1209. (d) Mastropaolo,
F.; Ricardo A. An. Asoc. Quim. Argent. 1940, 28, 101.
(12) Furstner, A.; Davies, P. W.; Lehman, C. W. Organometallics 2005,
24, 4065.
J. Org. Chem, Vol. 71, No. 22, 2006 8453

Koposov et al.
FIGURE 1. CAMERON drawing of the molecule 8c at the 50%
probability level (all hydrogen atoms are omitted for clarity). Close
contact within the molecule is shown with a dashed line.
FIGURE 3. CAMERON drawing of the polymeric chain formed by
the molecules of 8c at the 50% probability level (all hydrogen atoms
are omitted for clarity). Close contacts between the molecules are shown
with a dashed line.
FIGURE 2. CAMERON drawing of the molecule 8d at the 50%
probability level (all hydrogen atoms are omitted for clarity). Close
contact within the molecule is shown with a dashed line.
TABLE 1. Selected Interatomic Distances and Bond Angles in
Structures 8c and 8d
compound 8c
compound 8d
bond or
bond angle
distance (Å) or
angle (deg)
bond or
bond angle
distance (Å) or
angle (deg)
I1-C4
2.096
1.803
1.806
2.882
2.740
2.681
101.36
I1-C12
I1-O2
2.108
1.793
1.792
2.931
2.759
2.899
103.00
I1-O2
I1-O3
I1-O3
I1‚‚‚O6
O2‚‚‚I1
O3‚‚‚I1
O2-I-O3
I1‚‚‚O4
O2‚‚‚I1
O3‚‚‚I1
O2-I-O3
ecules. According to HRMS experiments, these oligomeric
chains also exist in the solution of compounds 8, as indicated
by the presence of 2M+ and 3M+ peaks in the mass spectra.
The average intermolecular I‚‚‚O distances in the crystal struc-
ture of the butyl ether 8d are about 0.1 Å longer then those in
the isopropyl ether of 2-iodylphenol 8c (Table 1). The relatively
weaker intermolecular interactions in the case of the butyl ether
of 2-iodylphenol 8d can be explained by the presence of the
moreflexiblebutylgroup. Thepresenceofthestrongerintermolec-
ular interactions in 2-iodylphenol ether 8c compared to 8d
provides explanation for the better solubility of compound 8d.
Oxidations with 2-Iodylphenol Ethers. To determine the
scope of the reactivity of 2-iodylphenol ethers 8, we have
performed a set of oxidation reactions with organic sulfides and
alcohols. To compare the influence of the crystal packing and
solublility on the reactivity, the reagents 8c and 8d with known
X-ray crystal structure were selected.
FIGURE 4. CAMERON drawing of polymeric chain formed by the
molecules of 8d at the 50% probability level (all hydrogen atoms are
omitted for clarity). Close contacts between the molecules are shown
with a dashed line.
reactions of IBX-esters.8 The oxidation proceeds smoothly under
reflux in acetonitrile within several hours. To determine the
scope and limitations of this procedure, we have oxidized a
variety of sulfides using reagents 8c and 8d (Table 2). The
reaction was found to be compatible with the presence of
different substituted phenyl rings as well as benzylic carbons.
The oxidation is limited to the sterically nonhindered sulfides,
and thus, no reaction occurred with tert-butyl sulfide even after
48 h (entry 11). Likewise, the oxidation does not occur when
The oxidation of sulfides was carried out with 0.6 equiv of
reagent 8 under conditions previously used in the similar
8454 J. Org. Chem., Vol. 71, No. 22, 2006

2-Iodylphenol Ethers
TABLE 2. Oxidation of Sulfides to Sulfoxides with Reagents 8c and 8da
a All reactions were carried out under reflux conditions in acetonitrile using 0.6 equiv of reagent 8. b All yields listed in the table are the yields of products
isolated after column chromatography. c All products were identified by comparison of their NMR data with those reported in the literature. d No oxidation
product was observed.
the strong electron-withdrawing moieties (e.g., CF3 group) are
present in the molecule (entry 8). No significant difference in
reactivity between reagents 8c and 8d was observed in the
oxidation of sulfides.
The reaction conditions for the oxidation of alcohols were
optimized using indanol as substrate. Chloroform under reflux
conditions was found to be the best solvent for this reaction.
We have found, however, that this oxidation is very sensitive
to the presence of traces of hydrochloric acid as an impurity in
chloroform. The use of unpurified chloroform leads to the
formation of indene due to the dehydration of indanol under
reaction conditions. To avoid this side reaction, chloroform
J. Org. Chem, Vol. 71, No. 22, 2006 8455

Koposov et al.
TABLE 3. Oxidation of Alcohols to Carbonyl Compounds with Reagents 8c and 8da
a All reactions were carried out under reflux conditions in chloroform using 1 equiv of reagent 8. b Reaction mixtures were analyzed by GC-MS; only
the indicated carbonyl compound was observed in each oxidation with conversion over 99%.
SCHEME 3
should be distilled and additionally purified by treatment with
basic aluminum oxide. In other solvents, such as ethyl acetate,
methylene chloride, and acetonitrile, the oxidation of indanol
was extremely slow. A wide range of alcohols can be oxidized
to the respective carbonyl compounds using reagents 8c and
8d in chloroform under reflux. It should be noted that the
oxidation of benzylic and allylic alcohols proceeds fast and does
not depend on the solubility of the hypervalent iodine reagent.
In contrast, the oxidation of saturated alcohols (e.g., cyclo-
heptanol and n-octanol) proceeds noticeably slower, and the
difference in solubilities between 8c and 8d starts to play a
significant role, as indicated by the longer reaction time of the
less soluble reagent 8c (Table 3, entries 3 and 4). It should be
also noted that this oxidation requires 1 equiv of the reagent 8,
and the trivalent iodine species 9 are formed as side products
as confirmed by the NMR experiment (Scheme 3). In particular,
these experiments: 4-(methylthio)benzyl alcohol and 2-(phen-
ylthio)ethanol. The reactions were carried out in both chloroform
and acetonitrile, and the product ratio was determined by H
1
NMR spectroscopy or preparative TLC. In the case of 4-(meth-
ylthio)benzyl alcohol, all three possible products of oxidation
were detected in the reaction mixture, as well as a small amount
of the starting material (Table 4). It should be noted that the
results obtained for both solvents are qualitatively similar;
however, in acetonitrile the sulfoxide was a major product of
the reaction while in chloroform both aldehyde and sulfoxide
were detected in approximately equal amounts.
1
the H and 13C NMR spectra of the reaction mixture from the
oxidation of ethanol with reagent 8d in CDCl3 clearly show
the disappearance of the C-IO2 signal at 135.6 ppm correspond-
ing to the reagent 8d and the emergence of the signal at 133.3
ppm of the C-IO carbon in trivalent iodine derivative 9 (Ar )
2-BuOC6H4). Further heating of the reaction mixture leads to
the extremely slow disproportionation of the trivalent iodine
species 9 (around 1% conversion over 24 h) with the formation
of compounds 8 and 7.
Similar results were obtained from the oxidation of 2-(phen-
ylthio)ethanol (Table 5). The reactions in both acetonitrile and
chloroform afforded sulfoxide as a major product and aldehyde
as a minor product.
To estimate the selectivity of oxidations with reagents 8, we
investigated the reactions of substrates containing both sulfide
and hydroxyl functional groups. Two alcohols were tested in
8456 J. Org. Chem., Vol. 71, No. 22, 2006

2-Iodylphenol Ethers
TABLE 4. Oxidation of 4-(Methylthio)benzyl Alcohol with Reagent 8d
a
The ratio of the products was determined by 1H NMR spectroscopy based on the integral intensity of signals corresponding to the methyl groups. b The
reaction was stopped after refluxing the solution of substrate and reagent 8d (1 equiv) in MeCN for 15 h. c The reaction was stopped after refluxing the
solution of substrate and reagent 8d (1 equiv) in chloroform for 3 h.
TABLE 5. Oxidation of 2-(Phenylthio)ethanol with the Reagent 8d
a The ratio of the products was determined by 1H NMR spectroscopy based on the integral intensity of signals corresponding to the methyl groups. b The
reaction was stopped after refluxing the solution of substrate and reagent 8d (1 equiv) in MeCN for 15 h. c The reaction was stopped after refluxing the
solution of substrate and reagent 8d (1 equiv) in chloroform for 3 h.
3H); 13C NMR (DMSO-d6) δ 157.4, 137.6, 134.6, 124.5, 122.3,
113.1, 57.4; ESI HRMS m/z 288.9334 (100) [M + Na]+. Anal.
Calcd for C7H7IO3: C, 31.60; H, 2.65; I, 47.70. Found: C, 31.79;
H, 2.62; I, 47.63.
1-Iodyl-2-propoxybenzene (8b). Oxidation of 1-iodo-2-pro-
poxybenzene 7b (0.261 g, 1.0 mmol) according to the general
procedure afforded 0.262 g (89%) of product 8b, isolated as white
crystals: mp 199-201 °C dec; 1H NMR (CDCl3) δ 7.85 (dd, J )
7.8, 1.5 Hz, 1H), 7.47 (td, J ) 7.8, 1.7 Hz, 1H), 7.13 (td, J ) 7.7,
1.0 Hz, 1H), 6.95 (dd, J ) 8.0, 0.7 Hz, 1H), 4.04 (t, J ) 6.6 Hz,
2H), 1.82 (m, 2H), 1.01 (t, J ) 7.5 Hz, 3H); 13C NMR (CDCl3) δ
156.9, 135.5, 134.9, 126.1, 133.6, 122.7, 71.6, 22.3, 10.6; ESI
HRMS m/z 316.9685 (100) [M + Na]+. Anal. Calcd for C9H11IO3:
C, 36.76; H, 3.77. Found: C, 36.47; H, 3.95.
1-Iodyl-2-isopropoxybenzene (8c). Oxidation of 1-iodo-2-
isopropoxybenzene 7c (0.261 g, 1.0 mmol) according to the general
procedure afforded 0.223 g (76%) of product 8c, isolated as white
crystals: mp 200-202 °C dec; 1H NMR (DMSO-d6) δ 7.74 (dd, J
) 7.6, 1.5 Hz, 1H), 7.55 (td, J ) 7.7, 1.5 Hz, 1H), 7.24 (m, 2H),
4.78 (m, 1H), 1.31 (d, J ) 5.9 Hz, 6H); 13C NMR (DMSO-d6) δ
155.9, 138.7, 134.4, 124.7, 122.1, 115.0, 72.8, 22.5; ESI HRMS
m/z 316.9646 (30) [M + Na]+, 610.9834 (100) [2M + Na]+,
904.9814 (30) [3M + Na]+. Anal. Calcd for C9H11IO3: C, 36.76;
H, 3.77; I, 43.15. Found: C, 36.89; H, 3.59; I, 43.26.
A single crystal of product 8c suitable for X-ray crystallographic
analysis was obtained by slow evaporation of saturated methylene
chloride solution of this compound. A crystal (approximate dimen-
sions 0.30 × 0.30 × 0.80 mm3) was placed onto the tip of a 0.1
mm diameter glass capillary and mounted for a data collection at
293(2) K. A unit cell dimensions were determined using 25
reflections in the θ ) 15-18° range (a ) 6.2665(15) Å, b )
13.0901(15) Å, c ) 12.7349(17) Å, R ) 90°, â ) 102.746(14)°, γ
) 90°, V ) 1018.9(3) Å3). The data collection was carried out
using Mo KR radiation (graphite monochromator). The final set of
reflections was collected within 3.112-27.488 range of 2θ. The
intensity data were corrected for absorption and decay using Texan
10.3b program.13 The structure was solved using Bruker SHELXTL
Conclusion
In conclusion, we have reported the preparation, structural
characterization, and chemistry of ethers of 2-iodylphenol ethers,
the new soluble and nonexplosive pentavalent iodine reagents.
2-Iodylphenol ethers 8 can be conveniently prepared by the
dimethyldioxirane oxidation of the corresponding 2-iodophenol
ethers 7 and isolated as chemically stable, microcrystalline
products. Single-crystal X-ray diffraction analysis of 1-iodyl-
2-isopropoxybenzene 8c and 1-iodyl-2-butoxybenzene 8d re-
vealed pseudopolymeric arrangements in the solid state formed
by intermolecular interactions between IO2 groups of different
molecules. The weaker intermolecular interactions in 1-iodyl-
2-butoxybenzene 8d explain better solubility of this product
compared to 1-iodyl-2-isopropoxybenzene 8c. 2-Iodylphenol
ethers 8c and 8d can selectively oxidize sulfides to sulfoxides
and alcohols to the respective aldehydes or ketones.
Experimental Section
For general experimental methods and synthesis of starting
materials 7b-d, see the Supporting Information.
General Procedure for Oxidation of 2-Iodophenol Ethers 7.
Freshly prepared 0.1 M solution of dimethyldioxirane in acetone
(30 mL, 3.0 mmol) was added to a stirred mixture of the appropriate
2-iodophenol derivative 7 (1.0 mmol) in 5 mL of dry CH2Cl2 at 0
°C. The color of the solution immediately changed from colorless
to light yellow. The reaction mixture was stirred at room temper-
ature for 8 h, and the resulting white microcrystalline precipitate
was separated by filtration; then diethyl ether was added to the
filtered solution, and the additional precipitate was filtered. Both
precipitates were collected, washed with ether, and dried in a
vacuum to afford analytically pure products 8.
1-Iodyl-2-methoxybenzene (8a). Oxidation of 1-iodo-2-meth-
oxybenzene 7a (0.234 g, 1.0 mmol) according to the general
procedure afforded 0.20 g (75%) of product 8a, isolated as white
crystals: mp 181-182 °C (with decomposition); 1H NMR (DMSO-
d6) δ 7.76 (dd, J ) 7.8, 1.5 Hz, 1H), 7.60 (td, J ) 7.8, 1.5 Hz,
1H), 7.27 (t, J ) 7.4 Hz, 1H), 7.24 (d, J ) 8.3 Hz, 1H), 3.91 (s,
(13) TeXsan 10.3b. Rigaku Inc.. Tokyo, Japan, 1998.
J. Org. Chem, Vol. 71, No. 22, 2006 8457

Koposov et al.
software14 and refined using CRYSTALS for Windows package.15
The space group P21/c was determined on the basis of systematic
absences and intensity statistics. A direct-method solution provided
the most non-hydrogen atoms from the E-map. Full-matrix least
squares/difference Fourier cycles were performed which located
the remaining non-hydrogen atoms. All non-hydrogen atoms were
refined with anisotropic displacement parameters unless stated
otherwise. All hydrogen atoms were placed in ideal positions and
refined as riding atoms with relative isotropic displacement
parameters. The final full matrix least squares refinement converged
to R1 ) 0.0384 and wR2 ) 0.1051 (F2, 3σ). For further details on
the crystal structure of 8c, see the CIF file (Supporting Information).
1-Iodyl-2-butoxybenzene (8d). Oxidation of 1-iodo-2-butoxy-
benzene 7d (0.276 g, 1.0 mmol) according to the general procedure
afforded 0.248 g (90%) of product 8d, isolated as white crystals:
determined on the basis of systematic absences and intensity
statistics. A direct-methods solution provided the most of non-
hydrogen atoms from the E-map. Full-matrix least squares/
difference Fourier cycles were performed which located the
remaining non-hydrogen atoms. All non-hydrogen atoms were
refined with anisotropic displacement parameters unless stated
otherwise. All hydrogen atoms were placed in ideal positions and
refined as riding atoms with relative isotropic displacement
parameters. The final full matrix least squares refinement converged
to R1 ) 0.0453 and wR2 ) 0.1043 (F2, 3σ). For further details on
crystal structure of 8d, see the CIF file (Supporting Information).
General Procedure for Oxidation of Sulfides by Reagents 8c
and 8d. To a vigorously stirred mixture of reagent 8 (0.3 mmol)
in acetonitrile (5 mL) was added an appropriate sulfide (0.5 mmol),
and the solution was refluxed. The reaction mixture was refluxed
until complete disappearance of sulfide (monitored by TLC). Then
the mixture was evaporated, and the residue was separated by
column chromatography using an EtOAc/hexane mixture (1:2) as
eluent to yield the final sulfoxide.
General Procedure for Oxidation of Alcohols by Reagents
8c and 8d. To a vigorously stirred mixture of reagent 8 (0.05 mmol)
in freshly distilled and purified over basic aluminum oxide
chloroform (0.7 mL) was added an appropriate alcohol (0.05 mmol),
and the solution was refluxed. The reaction mixture was refluxed
until complete disappearance of alcohol (monitored by TLC). A
portion of the crude reaction mixture (0.1 mL) was passed through
1 cm of silica gel suspended in a pasteur pipet and eluted with
CH2Cl2 (1 mL) and then diluted to 3 mL and analyzed by GC-
MS.
1
mp 164-165 °C dec; H NMR (CDCl3) δ 7.90 (dd, J ) 8.1, 1.5
Hz, 1H), 7.51 (td, J ) 7.8, 1.5 Hz, 1H), 7.19 (t, J ) 7.8 Hz, 1H),
7.00 (d, J ) 7.8 Hz, 1H), 4.12 (t, J ) 6.7. Hz, 2H), 1.82 (m, 2H),
1.48 (m, 2H), 0.98 (t, J ) 7.3 Hz, 3H); 13C NMR (CDCl3) δ 156.8,
135.2, 134.9, 125.9, 122.5, 112.6, 69.7, 30.8, 19.1, 13.8; ESI HRMS
m/z 330.9789 (100) [M + Na]+. Anal. Calcd for C10H13IO3: C,
38.98; H, 4.25; I, 41.19. Found: C, 39.05; H, 4.35; I, 41.28.
A single crystal of 8d suitable for X-ray crystallographic analysis
was obtained by slow evaporation of its saturated methylene
chloride solution. A crystal (approximate dimensions 0.80 × 0.40
× 0.05 mm3) was placed onto the tip of a 0.1 mm diameter glass
capillary and mounted for a data collection at 293(2) K. The unit
cell dimensions were calculated from 25 reflections in the θ ) 15-
18° range (a ) 14.117(5) Å, b ) 12.342(3) Å, c ) 6.582(5) Å, R
) 90°, â ) 98.80(4)°, γ ) 90°, V ) 1133.3(10) Å3). The data
collection was carried out using Mo KR radiation (graphite
monochromator). The final set of reflections was collected within
0.993-26.925 range of 2θ. The intensity data were corrected for
absorption and decay using Texan 10.3b program.13 The structure
was solved using Bruker SHELXTL software14 and refined using
CRYSTALS for Windows package.15 The space group P21/n was
Acknowledgment. This work was supported by a research
grant from the National Science Foundation (CHE-0353541)
and NSF-MRI award CHE-0416157.
Supporting Information Available: Details of the experimental
procedures, spectroscopic data of the reaction products, and X-ray
data for the compounds 8c and 8d (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) SHELXTL-Plus V5.10, Bruker Analytical X-ray Systems, Madison,
WI.
(15) Betteridge, P. W.; Carruthers, J. R.; Copper, R. I.; Prout, K.; Watkin,
D. J. J. Appl. Crystallogr. 2003, 36, 1487.
JO0614947
8458 J. Org. Chem., Vol. 71, No. 22, 2006