6-membered pseudocyclic IBX acids: Syntheses, X-ray structural characterizations, and oxidation reactivities in common organic solvents

Article abstract of DOI:10.1021/jo101639j

We designed and synthesized λ⁵-cyclic periodinanes 1 and 2, which are homologous to IBX (1-hydroxy-1-oxo-1H-1λ⁵- benzo[d][1,2]iodoxol-3-one) by one carbon, to thwart close packing of molecules in the crystal lattice to permit solubility in common organic solvents and to facilitate oxidations with enhanced reactivity. The X-ray crystal structures revealed that both 1 and 2 exist in the solid state as pseudocyclic (PC) acids, i.e., 1PC and 2PC, and that the molecules in the lattice are less weakly associated as compared to those in the parent IBX due to the twisting introduced via the sp³ benzylic carbon. Both 1PC and 2PC are found to dissolve in palpable amounts in DCM and acetonitrile to allow oxidation of a variety of alcohols and sulfides to carbonyl compounds and sulfoxides in a facile manner. The subtle differences in the sterics due to methyl and ethyl substituents in 1PC and 2PC are found to manifest in contrasting reactivities in that the oxidations of alcohols occur faster with 2PC, while those of sulfides to sulfoxides occur more rapidly with 1PC.

Full text of DOI:10.1021/jo101639j

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6-Membered Pseudocyclic IBX Acids: Syntheses, X-ray
Structural Characterizations, and Oxidation Reactivities in Common
Organic Solvents
Jarugu Narasimha Moorthy,* Kalyan Senapati, and Keshaba Nanda Parida
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
moorthy@iitk.ac.in
Received August 24, 2010
We designed and synthesized λ5-cyclic periodinanes 1 and 2, which are homologous to IBX (1-hydroxy-
1-oxo-1H-1λ5-benzo[d][1,2]iodoxol-3-one) by one carbon, to thwart close packing of molecules in the
crystal lattice to permit solubility in common organic solvents and to facilitate oxidations with enhanced
reactivity. The X-ray crystal structures revealed that both 1 and 2 exist in the solid state as pseudocyclic
(PC) acids, i.e., 1PC and 2PC, and that the molecules in the lattice are less weakly associated as
compared to those in the parent IBX due to the twisting introduced via the sp3 benzylic carbon. Both
1PC and 2PC are found to dissolve in palpable amounts in DCM and acetonitrile to allow oxidation of a
variety of alcohols and sulfides to carbonyl compounds and sulfoxides in a facile manner. The subtle
differences in the sterics due to methyl and ethyl substituents in 1PC and 2PC are found to manifest in
contrasting reactivities in that the oxidations of alcohols occur faster with 2PC, while those of sulfides to
sulfoxides occur more rapidly with 1PC.
Introduction
IBX;a λ5-iodane (1-hydroxy-1-oxo-1H-1λ5-benzo[d][1,2]-
iodoxol-3-one);has usurped center stage due to its environ-
mentally benign attributes, easy accessibility, and remark-
able reactivity; the latter property continues to be exploited
for diverse organic transformations.2 Two serious limita-
tions, however, with the use of IBX are its insolubility in
common organic solvents with the exception of DMSO and
explosive nature at high temperatures.3 A common reason
for these two undesirable characteristics has been attributed
to the close packing of molecules in the crystal lattice via
halogen bonds, hydrogen bonds, and aromatic π-π stacking
interactions.4 A number of modifications continue to be
explored in pursuit of IBX analogues that overcome the
Hypervalent oxidation reagents have gained a lot of
importance in recent oxidation chemistry.1 In particular,
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8416 J. Org. Chem. 2010, 75, 8416–8421
Published on Web 11/23/2010
DOI: 10.1021/jo101639j
r
2010 American Chemical Society

Moorthy et al.
JOCArticle
CHART 1
SCHEME 1. The Synthetic Routes for the Preparation of
6-Membered IBX Acids 1 and 2
drawbacks with IBX.5 We recently showed that modified Me-
IBX (Chart 1) can be employed for oxidation of alcohols and
sulfides in common organic solvents such as acetone and
acetonitrile; in this case, the so-called hypervalent twisting
accelerates the rate of oxidation.6 In continuation of our
interest in exploring the reactions mediated by IBX,6,7 we were
inspired to explore the reactivity of λ5-cyclic (C) periodinanes,
1C and 2C, which are homologous to IBX by one carbon. We
expected such analogues to exhibit solubility in common
organic solvents in addition to improved reactivity based on
the following rationale: (i) introduction of additional sp3
carbon at the benzylic site was expected to render the structure
nonplanar and hence preclude stacking interactions in the solid
state to facilitate solubility; (ii) the dialkyl groups at the benzylic
position were surmised to render the iodine site sterically
encumbered to influence the reactivity;the fact that steric
acceleration of collapse of the alkoxyperiodinane intermediate
in IBX-mediated oxidation of alcohols by the so-called hyper-
valent twisting is well-known;8 and (iii) the possibility to
introduce chirality at the benzylic site in the close proximity
of I(V) center was deemed immensely appealing from the point
of view of developing chiral λ5-iodanes for asymmetric
oxidations.5j,9 Herein, we report that the periodinanes 1 and
2 exist in the solid state as pseudocyclic (PC) systems, i.e., 1PC
and 2PC, with no covalent bonding between iodine and oxygen
atoms as revealed by X-ray crystallography, yet exhibit high
reactivity in common organic solvents for oxidation of alcohols
and sulfides. The pseudocyclic IBXs correspond to a different
class of λ5-iodanes, and there is a keen interest,5a-h as with
cyclic IBXs,5i-q to unravel their reactivity in organic oxida-
tions.
Results and Discussion
Synthesis of Cyclic 6-Membered IBX Acids 1 and 2 and
Their X-ray Structural Characterizations. Syntheses of the
target oxidation reagents 1 and 2 were accomplished starting
from o-iodobenzyl cyanide, which was dialkylated10 and
subsequently hydrolyzed to give R-dialkyl-o-iodophenylace-
tic acid.11 Treatment of the latter with oxone in water at
70 °C led to dimethyl and diethyl λ5-periodinanes 1 and 2
(Scheme 1).12
(5) (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) Koposov, A. Y.; Litvinov, D. N.; Zhdankin, V. V.
Tetrahedron Lett. 2004, 45, 2719. (c) Zhdankin, V. V.; Litvinov, D. N.;
Koposov, A. Y.; Ferguson, M. J.; McDonald, R.; Tykwinski, R. R. Chem.
Commun. 2004, 106. (d) Ladziata, U.; Koposov, A. Y.; Lo, K. Y.; Willging,
J.; Nemykin, V. N.; Zhdankin, V. V. Angew. Chem., Int. Ed. 2005, 44, 7127.
(e) 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. (f)
Viktor, V.; Zhdankin, V. V.; Goncharenko, R. N.; Litvinov, D. N.; Koposov,
A. Y. ARKIVOC 2005, iv, 8. (g) Koposov, A. Y.; Karimov, R. R.; Geraskin,
I. M.; Nemykin, V. N.; Zhdankin, V. V. J. Org. Chem. 2006, 71, 8452. (h)
Mailyan, A. K.; Geraskin, I. M.; Nemykin, V. N.; Zhdankin, V. V. J. Org.
Chem. 2009, 74, 8444. (i) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991,
113, 7277. (j) Zhdankin, V. V.; Smart, J. T.; Zhao, P.; Kiprof, P. Tetrahedron
Lett. 2000, 41, 5299. (k) Thottumkara, A. P.; Vinod, T. K. Tetrahedron Lett.
2002, 41, 569. (l) Ozanne, A.; Pouysegu, L.; Depernet, D.; Francois, B.;
Quideau, S. Org. Lett. 2003, 5, 2903. (m) Nikiforov, V. A.; Karavan, V. S.;
Miltsov, S. A.; Selivanov, S. I.; Kolehmainen, E.; Wegelius, E.; Nissinen, M.
ARKIVOC 2003, vi, 191. (n) Meprathu, B. V.; Justik, M. W.; Protasiewicz,
J. D. Tetrahedron Lett. 2005, 46, 5187. (o) Richardson, R. D.; Zayed, J. M.;
Altermann, S.; Smith, D.; Wirth, T. Angew. Chem., Int. Ed. 2007, 46, 6529.
(p) Zhdankin, V. V.; Nemykin, V. N.; Karimov, R. R.; Kazhkenov, Z.-G.
Chem. Commun. 2008, 6131. (q) Uyanik, M.; Akakura, M.; Ishihara, K.
J. Am. Chem. Soc. 2009, 131, 251.
The single crystals of dimethyl and diethyl homologous
IBXs 1 and 2 suitable for X-ray structure determinations
were grown from a TFA-DMF (1:2) mixture and DMF,
respectively. X-ray intensity data collection followed by
structure determination revealed that the asymmetric unit
cell in the case of 1 (triclinic, P1) contains two molecules of
the o-iodylphenyl-2-methylpropionic acid 1, i.e., A and B,
together with two molecules of trifluoroacetic acid, which
was used for crystallization. However, only one molecule
was found in the asymmetric unit cell of 2 (tetragonal,
P421c). Further, in both 1 and 2, the intra- and intermole-
cular contacts involving iodine and carboxy groups suggest
that the pentavalent iodine can only be considered as pseu-
docyclic, i.e., 1PC/2PC, and not as cyclic iodane, i.e., 1C/2C.
This is so despite the fact that intramolecular I O distances
3 3 3
for the two independent molecules in 1PC and that in 2PC
˚
are 2.404, 2.606, and 2.607 A. In general, for pseudocyclic
˚
iodyl compounds, the I O distance is higher than 2.60 A,
3 3 3
(6) Moorthy, J. N.; Singhal, N.; Senapati, K. Tetrahedron Lett. 2008,
49, 80.
˚
and any value in the range of 2.20-2.50 A is considered to
classify the molecular system as corresponding to cyclic
(7) (a) Moorthy, J. N.; Singhal, N.; Mal, P. Tetrahedron Lett. 2004, 45,
309. (b) Moorthy, J. N.; Singhal, N.; Venkatakrishnan, P. Tetrahedron Lett.
2004, 45, 5419. (c) Moorthy, J. N.; Singhal, N.; Senapati, K. Tetrahedron
Lett. 2006, 47, 1757. (d) Moorthy, J. N.; Singhal, N.; Senapati, K. Org.
Biomol. Chem. 2007, 5, 767. (e) Moorthy, J. N.; Senapati, K.; Singhal, N.
Tetrahedron Lett. 2009, 50, 2493. (f) Moorthy, J. N.; Senapati, K.; Kumar, S.
J. Org. Chem. 2009, 74, 6287.
iodane as opposed to pseudocyclic iodyl derivative.5p The
O-H O intermolecular hydrogen bonds involving the
3 3 3
carboxy groups unambiguously establish the nature of 1
(8) Su, J. T.; Goddard, W. A., III J. Am. Chem. Soc. 2005, 127, 14146.
(9) (a) Quideau, S.; Lyvinec, G.; Marguerit, M.; Bathany, K.; Ozanne-
(10) Yamashita, M.; Ono, Y.; Tawada, H. Tetrahedron 2004, 60, 2843.
(11) Kolotuchin, S. V.; Thiessen, P. A.; Fenlon, E. E.; Wilson, S. R.;
Loweth, C. J.; Zimmerman, S. C. Chem.;Eur. J. 1999, 5, 2537.
(12) Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64,
4537.
ꢀ
ꢀ
Beaudenon, A.; Buffeteau, T.; Cavagnat, D.; Alain Chenede, A. Angew.
Chem., Int. Ed. 2009, 48, 4605. (b) Ladziata, U.; Carlson, J.; Zhdankin, V. V.
Tetrahedron Lett. 2006, 47, 6301.
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FIGURE 1. The perspective drawings of the molecular structures and crystal packing diagrams of pseudocyclic IBX acids 1PC (top) and 2PC
(bottom).
and 2 as pseudocyclic (PC). The molecular structures of both
1PC and 2PC are shown in Figure 1. As expected, the struc-
tures are nonplanar with the sp3 carbon introducing a twist
to render the molecules quite skewed. The relevant bond
distances and intramolecular contacts for both 1PC and 2PC
are given in Tables S1 and S2 (Supporting Information).
The crystal packing of 1PC (Figure 1) reveals the forma-
been ortho-substitution, proposed initially by Protasiewicz.13
On the basis of this concept, Zhdankin and co-workers have
synthesized a variety of stable and soluble pseudocyclic 2-
iodylbenzenes, and demonstrated their reactivities in the oxi-
dation of alcohols and sulfides.5a-h,j,p Some of the notable
pseudocyclic IBXs include IBX-amides,5a 2-iodoxybenzene-
sulfamides,5b N-(2-iodylphenyl)acylamides,5d IBX esters,5e
2-iodoxybenzenesulfonate esters,5f IBX ethers,5g N-(2-iodyl-
phenyl)tosylamides,5h 2-iodylphenyl tosylates,5h etc. Of these,
only N-(2-iodylphenyl)tosylamides, 2-iodylphenyl tosylates,
and N-(2-iodylphenyl)acylamides correspond to 6-membered
pseudocyclic IBXs. It is intriguing that in the present investiga-
tion, 1-carbon homologation in 1 and 2 leads to 2-iodylphe-
nylacetic acids instead of cyclic structures as in the case of
parent IBX. Presumably, the crystal packing stabilization is
higher when the crystallization proceeds through the acyclic
form than the cyclic tautomeric form. Notwithstanding the
finding that both methyl and ethyl homologous IBXs 1 and 2
exist in their pseudocyclic structures in the solid state, their
ability to accomplish oxidation of alcohols and sulfides was
explored. As noted earlier, there is lot of continuing interest in
exploring the reactivity of pseudocyclic IBXs.5a-h Incidentally,
6-membered pseudocyclic IBX homologues are scarce, and
their reactivity as oxidation reagents is of fundamental interest.
Initially, the screening studies were carried out with
p-bromobenzyl alcohol as the substrate. As shown in Table 1,
tion of strands that are built up by I O halogen bonds and
3 3 3
O-H O hydrogen bonds. A closer inspection shows that
3 3 3
the centrosymmetric partners of independent molecules A
and B are connected by IdO I halogen bonds; while the
3 3 3
iodyl moieties are interconnected for molecules A, iodine and
carbonyl oxygen of the carboxy group are involved for mole-
cules B. The centrosymmetrically related pairs of molecules
A and B are further O-H O bonded to make up the strands
3 3 3
as shown in Figure 1. The solvent TFA molecules are found to
be bound to axial oxygens via O-H O hydrogen bonds. In
3 3 3
2PC, one observes helical propagation of molecules (21-screw)
sustained by I O and O-H O bonds. The symmetry
3 3 3
3 3 3
related helices are further connected by O-H O hydrogen
3 3 3
bonds in a manner akin to a double helix. What is otherwise
noteworthy is that in both 1PC and 2PC, the intermolecular
association is a lot weaker when compared to that in the parent
IBX; in the latter, there exists a 2-dimensional close packing
into layers that are further close packed by aromatic stacking
interactions.4
Oxidation of Alcohols and Sulfides with 1PC and 2PC. One
of the ways to destroy polymeric network structures asso-
ciated with pentavalent iodyl arenes that are insoluble has
(13) Macikenas, D.; Skrzypczak-Jankun, E.; Protasiewicz, Z. D. Angew.
Chem., Int. Ed. 2000, 39, 2007.
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oxidation to the corresponding aldehyde was examined with
1PC and 2PC in DCM, CHCl3, acetonitrile, acetone, and ethyl
acetate as common organic solvents. Typically 1.5 equiv of the
reagent was employed for oxidation; although 1.05/1.10 equiv
of the reagent was found to be sufficient for DCM, excess
reagent, i.e., 1.5 equiv, was uniformly employed to ensure
complete conversion of the alcohol in all solvents and to reduce
the reaction times; indeed, the excess reagent was found to
facilitate complete conversion of less reactive alcohols, Table 2,
vide infra. It should be noted that the oxidation of p-bromo-
benzyl alcohol was found to be slow in acetone and ethyl
acetate (entries 7-10, Table 1). The oxidation occurred most
rapidly in DMSO (entries 11 and 12, Table 1). A perusal of the
results in Table 1 show that diethyl analogue, i.e., 2PC, per-
forms better and that the oxidation occurs in a facile manner in
DCM at room temperature; while the conversion of p-bromo-
benzyl alcohol to p-bromobenzaldehyde occurred in 6 h with
1PC (entry 1, Table 1), the oxidation was found to be complete
with 2PC in less than 2.5 h (entry 2). Thus, the oxidation of
diverse alcohols was examined at room temperature in DCM as
the solvent. As shown in Table 2, a variety of alcohols were
readily oxidized to the corresponding carbonyl compounds, the
reactions were found to occur considerably faster for diethyl
analogue, i.e., 2PC, than for 1PC. Insofar as the reactivities are
concerned, allylic (entries 7, 8, 13, and 14, Table 2), benzylic
(entries 1-6, 11, 12, 19, and 20, Table 2), and secondary
alcohols (entries 9, 10, 15, and 16, Table 2) were found to
undergo oxidation with comparable rates as reflected from the
durations of the reactions, while primary alcohols underwent
oxidation over relatively longer times (entries 17 and 18,
Table 2).
TABLE 1. Results of Solvent Screening Studies for the Oxidation of
Representative p-Bromobenzyl Alcohol to p-Bromobenzaldehyde with
Pseudocyclic IBX Acids 1PC and 2PCa
aAll reactions were conducted on 0.5-1.0 mmol of the alcohol at
room temperature (25-30 °C). bIsolated yields. c40% unreacted starting
compound was isolated.
TABLE 2. Results of Oxidation of a Variety of Alcohols to the
Corresponding Carbonyl Compounds with Pseudocyclic IBX Acids 1PC
and 2PC in DCM at Room Temperaturea
The reduction products of both 1PC and 2PC were
identified to be the corresponding I(III) species, viz., 2-
(o-iodosophenyl)-2-methylpropionic acid and 2-ethyl-2-
(o-iodosophenyl) butanoic acid, cf. eq 1.
While the IR spectral analysis indicates the cyclic structure
with no evidence for the free carboxyl group, the solution
state NMR spectra reveal both cyclic as well as acyclic
species in equilibrium (eq 1); one observes two sets of signals
1
in both H and 13C NMR spectra, an observation that has
been noted by others as well,5d cf. SI.
Buoyed by the reactivity of pseudocyclic IBXs 1 and 2 in
the oxidation of alcohols at rt and selectively in the case of
primary alcohols, we examined the oxidation of a few select
sulfides. The oxidations were performed in a neutral solvent
such as acetonitrile by employing 1.1 equiv of 1PC/2PC.
While the reactions were found to be sluggish at rt, the
sulfoxides were found to be formed at higher temperatures.
The dialkyl sulfide such as ethyl n-octyl sulfide reacted in
1-3 h with 1PC and 2PC to yield the corresponding sulf-
oxide in a quantitative yield (entries 1and 2, Table 3). The
methyl phenyl sulfide reacted likewise to afford the sulfoxide
in ca. 80% isolated yield (entries 3 and 5, Table 3). While the
unsubstituted diphenyl sulfide and p-methoxy-substituted
aAll reactions were conducted on 0.5-1.0 mmol of the alcohol at
room temperature (25-30 °C). bIsolated yields. cReactions were per-
formed at 20 °C.
analogue were found to be oxidized, albeit the former over a
longer period of time (entries 7-10, Table 3), the oxidation
of p-nitro analogue was found to be extremely sluggish
(entries 11 and 13, Table 3). Nonetheless, a limited, yet
meaningful set of substrates show clearly that the pseudo-
cyclic IBXs 1PC and 2PC serve as oxidation reagents for the
oxidation of dialkyl and e-rich diarylsulfides under neutral
conditions. It is noteworthy that overoxidation to sulfones
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TABLE 3. Results of Oxidation of Sulfides with 1PC and 2PC in
Acetonitrilea
example, the oxidation of methyl phenyl sulfide and
p-nitrophenyl phenyl sulfide was found to occur with 0.55
equiv of 1PC and 2PC (entries 4 and 6, Table 3), see the SI.
Even the less reactive p-nitrophenyl phenyl sulfide underwent
reaction at rt (entries 12 and 14, Table 3). The end product of
iodine reagent was found to be 2-(o-iodophenyl)-2-methylpro-
pionic acid/2-ethyl-2-(o-iodophenyl)butanoic acid, which sug-
gests 4e-reduction in the overall conversion of sulfides to
sulfoxides.
Mechanistic Considerations. Insofar as alcohol oxidations
are considered, the results of oxidations with 1PC/2PC are
indeed very facile and occur at rt when compared with the
reactivities reported for other pseudocyclic analogues.5a-h
In particular, 2PC is found to work better than 1PC. The
reverse is found to hold true for sulfide oxidations. In
addition to these intriguing observations, the question that
springs up is: which of the two species, i.e., cyclic (C) and
pseudocyclic (PC) in Chart 1, is responsible for oxidation,
although pseudocyclic structure is revealed by X-ray crystal-
lography in the solid state. The 1H NMR analyses in DMSO
did not reveal any evidence for the presence of two species,
while IR analyses in DCM were not possible due to poor
solubilities (0.36 g/L for 1PC and 0.45 g/L for 2PC). The
possibility that the cyclic species in equilibrium may con-
tribute to the overall observed oxidations to some degree
cannot be ruled out. We believe that the origin of contrasting
differences in the reactivities of dimethyl (1PC) and diethyl
(2PC) homologous IBXs in regard to alcohol and sulfide
oxidations should be traceable to the way the sterics asso-
ciated with methyl and ethyl groups exert influence on the
rate-determining steps of the two oxidation reactions, which
clearly appear to follow distinct mechanisms.
aAll reaction were carried out on 0.5-1 mmol of the sulfide in
acetonitrile at reflux by employing 1.1 equiv of the reagent, unless
mentioned otherwise. bIsolated yields based on consumed starting
compound. cThe reaction was carried out at 50 °C. dThe reagent (0.55
equiv) and TFA (5 equiv) were employed and the reactions were
conducted at room temperature in CHCl3. eCa. 20% unreacted starting
compound was recovered. fCa. 45-50% starting compound was recov-
ered. gThe reaction was too sluggish, and 84% unreacted starting
compound was recovered.
was observed for none of the cases. The 1H NMR monitoring
studies of the oxidations with 1PC and 2PC revealed the
formation of their iodo acid precursors together with 2-(o-
iodosophenyl)-2-methylpropionic acid or 2-ethyl-2-(o-iodo-
sophenyl)butanoic acid-I(III) species (eq 2).
Conclusions
6-Membered homologues of IBXs 1 and 2 were designed
to overcome the insolubility of parent IBX in common
organic solvents and influence oxidation reactivity via ste-
rics. The X-ray crystal structure analyses revealed the struc-
tures of homologous IBXs to be pseudocyclic in the solid
state, i.e., 1PC and 2PC. The X-ray crystal packing analyses
show that the molecules are twisted due to the sp3 carbon at
the benzylic site, which is doubly alkylated. The nonplanar-
ity seemingly renders the crystal packing rather less cluttered
in comparison to that in parent IBX. Both pseudocyclic IBXs
1 and 2 are found to exhibit comparable, but palpable
solubility in common organic solvents to permit oxidation
of diverse alcohols and sulfides in common organic solvents.
In alcohol oxidations, 2PC is found to perform better than
1PC, while the latter is found to be better for sulfide oxida-
tions. This difference in reactivities should be a result of the
influence of sterics associated with methyl and ethyl groups
on the seemingly contrasting mechanisms of oxidation of
alcohols and sulfides. The results demonstrate the viability to
manipulate the reactivities by steric effects. Given that the
substituents in structures 1 and 2 at the benzylic site evidently
modify the reactivity and that the chirality can be intro-
duced readily to develop chiral IBXs, analogous chiral
oxidation reagents are likely to be very promising for en-
antioselective oxidations. We are continuing our efforts to
develop chiral IBXs for application in enantioselective oxi-
dation chemistry.
The formation of 2-(o-iodophenyl)-2-methylpropanoic acid
or 2-ethyl-2-(o-iodophenyl)butanoic acid suggests that the
intermediate I(III) species also undergoes further reduc-
tion.14 This process, however, appears to be substrate-de-
pendent as suggested by the formation of iodo acid in varying
amounts (ca. 10-50%); it is for this reason that the reagent
was employed in 1.1 equiv uniformly for the sulfide to sulf-
oxide oxidations. Quite remarkably, the oxidation was found
to occur very rapidly in the presence of added TFA. For
(14) The reduction product, i.e., I(III) species, failed to oxidize the
alcohols. Further, 0.55 equiv of the IBX acid (1PC/2PC) was found to be
sufficient for complete conversion of a sulfide such as methyl phenyl sulfide
to the corresponding sulfoxide in the presence of TFA, cf. SI. These two
considerations preclude the possibility of disproportionation of I(III) species
to I(V) and I(I), and hence as the origin of I(I) species in sulfide oxidations.
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JOCArticle
Experimental Section
mmol) of 2-ethyl-2-(2-iodophenyl)butanenitrile was taken in a
mixture of AcOH (30 mL) and 60% H2SO4 (40 mL) and heated
at 120 °C overnight. The reaction mixture was allowed to cool to
rt. Subsequently, 6.0 g (4.0 equiv, 86.96 mmol) of NaNO2 was
added and heating was continued at 90 °C for another 2 h. Later,
the reaction mixture was poured into crushed ice and the
product was filtered under cold conditions (yield 86%). Color-
less solid; mp 153-155 °C; IR (KBr) cm-1 2979, 2637, 1701;
1H NMR (400 MHz, CDCl3) δ 0.74 (t, J=7.6 Hz, 6H), 2.03 (m,
2H), 2.33 (m, 2H), 6.92 (t, J = 7.5 Hz, 1H), 7.29-7.36 (m, 2H),
7.94 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
8.5, 25.8, 56.9, 98.7, 127.5, 128.4, 129.2, 142.3, 143.0, 181.3;
ESI-MS þ m/z calcd for C12H15IO2 319.0195 [M þ H], found
319.0195.
Preparation of 2-Ethyl-2-(2-iodylphenyl)butanoic Acid, 2PC.
To a solution of 11.6 g (2.0 equiv, 18.87 mmol) of oxone in 50 mL
of distilled water at 70 °C was added 3.0 g (1.0 equiv, 9.43 mmol)
of 2-ethyl-2-(2-iodophenyl)butanoic acid slowly. The stirring
was continued at 70 °C for 4 h. 2-Ethyl-2-(2-iodylphenyl)-
butanoic acid (2PC) was obtained as a colorless solid (2.8 g,
yield 85%). Mp 166-168 °C; IR (KBr) cm-1 3435, 2978, 2469,
2227, 1646, 798, 737; 1H NMR (400 MHz, DMSO-d6) δ 0.62 (t,
J=7.3 Hz, 6H), 2.05-2.13 (m, 4H), 7.53-7.57(m, 3H), 8.18-
8.20 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 9.3, 31.4, 55.0,
127.1, 128.1, 130.1, 131.4, 141.6, 148.5, 178.7; ESI-MS þ m/z
calcd for C12H15IO4 348.9937 [M - H], found 348.9934.
General Procedure for Oxidation of Alcohols with 1PC and
2PC in DCM. In a typical experiment, 0.5-1.0 mmol of the
alcohol in 10.0 mL of DCM was stirred for 5-10 min and to this
was introduced 1.5 equiv of 1PC/2PC. The reaction mixture was
stirred for the appropriate duration at room temperature (see
Table 2). The progress of the reaction was monitored by TLC
analysis. After completion of the reaction, the solid material
from the reaction mixture was filtered in vacuo. Concentration
of the filtrate afforded the product, which was subjected to silica
gel column chromatography to isolate the pure product.
General Procedure for Oxidation of Sulfides with 1PC and
2PC in CH3CN. In a typical experiment, 0.5-1.0 mmol of the
sulfide was taken in 10.0 mL of CH3CN and to it 1.1 equiv of
modified IBX (1PC/2PC) was introduced. The reaction mixture
was stirred for the appropriate duration and temperature (see
Table 3). The progress of the reaction was monitored by TLC
analysis. After completion of the reaction, the solid material
from the reaction mixture was filtered in vacuo. Concentration
of the filtrate afforded the product, which was subjected to silica
gel column chromatography to isolate the pure product.
Preparation of 2-(2-Iodophenyl)-2-methylpropanenitrile.15
A
solution of 6.64 g (4.2 equiv, 69.13 mmol) of tBuONa in 22 mL of
a 1:1 mixture of 1-methylpyrrolidin-2-one (NMP) and THF was
cooled to 0 °C under nitrogen atmosphere. Into this solution was
introduced 4.0 g (1.0 equiv, 16.46 mmol) of o-iodobenzylcyanide
followed by 4.65 mL (4.5 equiv, 74.07 mmol) of methyl iodide
dropwise. The reaction mixture was allowed to stir for 4 h at rt.
Subsequently, the reaction was quenched with water at ice cold
condition and extracted with CHCl3. The combined extracts
were dried over anhydrous Na2SO4 and solvent stripped in
vacuo. Silica gel column chromatography of the residue led to
the isolation of 3.97 g of 2-(2-iodophenyl)-2-methylpropaneni-
trile (yield 89%). Colorless liquid; 1H NMR (400 MHz, CDCl3)
δ 1.91 (s, 6H), 6.99 (td, J1 = 7.6 Hz, J2 = 1.4 Hz, 1H), 7.38 (td,
J1=7.6 Hz, J2 = 1.0 Hz, 1H), 7.45 (dd, J1 = 7.8 Hz, J2 = 1.4 Hz,
1H), 8.03 (dd, J1 = 7.8 Hz, J2=1.0 Hz, 1H).
Preparation of 2-(2-Iodophenyl)-2-methylpropanoic Acid. A
solution of 4.0 g (1.0 equiv, 14.76 mmol) of 2-(2-iodophenyl)-2-
methylpropanenitrile in a mixture of AcOH (15 mL) and 60%
H2SO4 (30 mL) was heated at 120 °C for 2 h. The reaction
mixture was allowed to cool to room temperature. Subse-
quently, 5.09 g (5.0 equiv, 73.80 mmol) of NaNO2 was added
slowly, and the reaction mixture was heated at 90 °C for another
2 h. After the completion of the reaction, it was poured into
crushed ice, and the mixture was filtered (yield 82%). Colorless
solid; mp 134-136 °C; IR (KBr) cm-1 2982, 1692; H NMR
1
(400 MHz, CDCl3) δ 1.71 (s, 6H), 6.93 (td, J1 = 7.6 Hz, J2 = 1.7
Hz, 1H), 7.33-7.42 (m, 2H), 7.92 (d, J = 7.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 26.8, 50.0, 98.6, 127.0, 128.2, 128.5, 141.9,
145.6, 182.9; ESI-MS þ m/z calcd for C10H11IO2 290.9882
[M þ H], found 290.9884.
Preparation of 2-(2-Iodylphenyl)-2-methylpropanoic Acid,
1PC. To a solution of 12.72 g (2 equiv, 20.68 mmol) of oxone
in 50 mL of distilled water was added 3.0 g (1.0 equiv, 10.34
mmol) of 2-(2-iodophenyl)-2-methylpropanoic acid gradually.
The stirring was continued for 4 h at 70 °C. The product, i.e.,
2-(2-iodylphenyl)-2-methylpropanoic acid (1PC), was obtained
as a colorless solid, which was filtered, washed with cold
acetone, and dried (2.43 g, yield 73%). Mp 161-163 °C; IR
(KBr) cm-1 3445, 2493, 2980, 1657, 1207, 752, 732; H NMR
1
(500 MHz, DMSO-d6) δ 1.63 (s, 6H), 7.57-7.62 (m, 3H),
8.16-8.18 (m, 1H); 13C NMR (125 MHz, DMSO-d6) δ 29.0,
46.3, 127.1, 127.5, 128.2, 131.9, 144.6, 148.3, 179.7; ESI-MS þ
m/z calcd for C10H11IO4 322.9780 [M þ H], found 322.9782.
Preparation of 2-Ethyl-2-(2-iodophenyl)butanenitrile.16 A sim-
ilar procedure as described above with ethyl iodide led to 2-ethyl-
2-(2-iodophenyl)butanenitrile in 92% isolated yield. Colorless
liquid; 1H NMR (400 MHz, CDCl3) δ 0.91 (t, J = 7.6 Hz,
6H), 2.02 (m, 2H), 2.72 (m, 2H), 6.98 (t, J = 7.6 Hz, 1H), 7.37
(t, J = 7.8 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 8.00 (d, J =
7.8 Hz, 1H).
Acknowledgment. J.N.M. is thankful to the Department
of Science and Technology (DST), India for generous finan-
cial support. K.S. and K.P. gratefully acknowledge the
senior research fellowships from UGC and CSIR, respec-
tively. We thank the anonymous referees for their invaluable
suggestion and criticism.
Preparation of 2-Ethyl-2-(2-iodophenyl)butanoic Acid. As de-
scribed above for the dimethyl analogue, 6.50 g (1.0 equiv, 21.74
Supporting Information Available: Characterization data,
spectra for the products, 1H and 13C spectral reproductions for
1PC and 2PC, and crystal data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(15) Kesharwani, T.; Verma, A. K.; Emrich, D.; Ward, J. A.; Larock.,
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(16) Pascal, C.; Dubois, J.; Guenard, D.; Tchertanov, L.; Thoret, S.;
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Gueritte, F. Tetrahedron 1998, 54, 14737.
J. Org. Chem. Vol. 75, No. 24, 2010 8421