In situ generation of o-lodoxybenzoic acid (IBX) and the catalytic use of it in oxidation reactions in the presence of oxone as a co-oxidant

Article abstract of DOI:10.1021/ol050875o

(Chemical Equation Presented) Catalytic use of o-iodoxybenzoic acid (IBX) in the presence of Oxone as a co-oxidant is demonstrated for the oxidation of primary and secondary alcohols in user- and eco-friendly solvent mixtures. Also demonstrated is the in situ (re)oxidation of 2-iodosobenzoic acid (IBA) and even commercially available 2-iodobenzoic acid (2IBAcid) by Oxone to IBX allowing one to use these less hazardous reagents, in place of potentially explosive IBX, as catalytic oxidants.

Full text of DOI:10.1021/ol050875o

ORGANIC
LETTERS
2
005
Vol. 7, No. 14
933-2936
In Situ Generation of o-Iodoxybenzoic
Acid (IBX) and the Catalytic Use of It in
Oxidation Reactions in the Presence of
Oxone as a Co-oxidant
2
Arun P. Thottumkara, Michael S. Bowsher, and Thottumkara K. Vinod*
Department of Chemistry, Western Illinois UniVersity, Macomb, Illinois 61455
mftkV@wiu.edu
Received April 20, 2005
ABSTRACT
Catalytic use of o-iodoxybenzoic acid (IBX) in the presence of Oxone as a co-oxidant is demonstrated for the oxidation of primary and
secondary alcohols in user- and eco-friendly solvent mixtures. Also demonstrated is the in situ (re)oxidation of 2-iodosobenzoic acid (IBA)
and even commercially available 2-iodobenzoic acid (2IBAcid) by Oxone to IBX allowing one to use these less hazardous reagents, in place
of potentially explosive IBX, as catalytic oxidants.
2
b
Within the past decade, o-iodoxybenzoic acid (IBX) has
emerged as a powerful yet selective oxidant that effects a
plethora of oxidative transformations in synthetic organic
chemistry. The synthetic use of IBX as an oxidizing agent
was initially demonstrated by Frigerio and Santagostino for
the selective transformation of alcohols to carbonyl com-
dithioketals, and selective deprotection of triethylsilyl ethers
in the presence of tert-butyldimethylsilyl (TBDMS) ethers,3
in addition to the more conventional oxidation of alcohols
4
to carbonyl compounds. These transformations using IBX,
a potentially shock-sensitive explosive oxidant, are carried
5
out in DMSO, the only solvent in which the reagent readily
dissolves. The practical difficulty in using DMSO as the
solvent of choice for IBX reactions has prompted many
researchers to structurally modify IBX to produce efficient
and user-friendly derivatives that do not possess the deleteri-
ous explosive property of IBX and can be used in solvents
other than DMSO. The syntheses of solid-phase-anchored
1
pounds in 1994. The past few years have seen an explosive
growth in the demonstration and use of IBX as a selective
reagent for unique oxidative transformations including oxida-
tion of benzylic carbons,2 oxidation of amines, dehydro-
a
2b
genation of ketones and aldehydes to the corresponding R,â-
2a
unsaturated analogues, dehydrogenation of N-heterocycles
2b
to heteroaromatics, oxidative cleavage of dithioacetals and
(
3) Wu, Y.; Huang, J.-H.; Hu, Q.; Tang, C.-J.; Li, L. Org. Lett. 2002, 4,
2
141-2144.
(
1) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35, 8019-
022.
2) (a) Nicolaou, K. C.; Montagnon, T.; Baran, P. S.; Zhong, Y.-L. J.
(4) (a) De Munari, S.; Frigerio, M.; Sanatgostino, M. J. Org. Chem. 1996,
8
61, 9272-9279. (b) Frigerio, M.; Santagostino, M.; Sputore, S. J. J. Org.
(
Chem. 1999, 64, 4537-4538.
Am. Chem. Soc. 2002, 124, 2245-2258. (b) Nicolaou, K. C.; Mathison, C.
J. N.; Montagnon, T. J. Am. Chem. Soc. 2004, 126, 5192-5201.
(5) IBX is reported to be a shock-sensitive explosive. See: Plumb, J.
B.; Harper, D. J. Chem. Eng. News 1990, 68 (29), 3.
1
0.1021/ol050875o CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/07/2005

6
derivatives of IBX and a stabilized formulation of IBX are
carried out in aqueous THF provided only trace amounts of
the oxidized substrate along with substantial amounts of
γ-butyrolactone, an oxidized product of THF. This solvent
system was thus deemed inappropriate for our study. Though
reactions carried out in both 1:1 and 2:1 v/v mixtures of
acetonitrile and water yielded oxidized products, significant
differences in the yields of the products in the two solvent
system were not noted. For example, oxidation of 3-phenyl-
1-propanol using 0.3 equiv of IBX and 0.5 equiv of Oxone
as the co-oxidant gave 3-phenylpropanoic acid in 51% and
58%, respectively. The yield of the acid product was, how-
ever, above 90% in both solvent systems when the amount
of Oxone was increased to 1.5 equiv. These results from
our initial but limited solvent optimization studies were
encouraging and significant for the following reasons. The
product from the four attempts were the corresponding
carboxylic acid and not the aldehyde, the usual oxidation
7
noteworthy examples in this area. A contribution from this
laboratory has also described the synthesis of a water-soluble
derivative of IBX as a selective oxidant for allylic and ben-
zylic alcohols. Moreover, a report from Finney Laboratories
describes the use of IBX in common organic solvents, such
as acetonitrile, acetone, ethyl acetate and toluene at elevated
8
9
temperatures, thus enhancing the popularity of the reagent.
A research objective of an ongoing project in our labora-
tory is to develop user- and eco-friendly protocols for
oxidation of alcohols and other substrates using environ-
mentally safe reagents and solvents. As such, the benign
environmental character of IBX and other hypervalent iodine
reagents attracted our attention. The recently demonstrated
9
use of IBX as an oxidant in water-miscible organic solvents
and the fact that Oxone,10 an environmentally safe reagent,
oxidizes organoiodo compounds in aqueous solvent systems
to their hypervalent state prompted us to investigate the
oxidation of alcohols using catalytic amounts of IBX in the
presence of Oxone as a co-oxidant.11 Our planned strategy
4a,b
product of primary alcohols using IBX. Recently reported
easy oxidation of aldehydes to the corresponding acids using
Oxone clearly offers an explanation for the formation of acid
1
3
products from these reactions. Control oxidation reactions
carried out using Oxone and 3-phenyl-1-propanol returned
the starting alcohol, confirming the inability of Oxone to
oxidize alcohols to carbonyl compounds efficiently. The
formation of 3-phenylpropanoic acid in yields more than
3
0%, which would have been the maximum yield obtained
if IBX was not being regenerated in the reaction medium,
was gratifying and indicative of a ready reoxidation of IBA
back to IBX during the reaction. At this juncture we realized
that the implications of this observation go beyond the simple
regeneration of IBX but also allude to the possibility of using
the less hazardous IBA or even commercially available
is the in situ reoxidation of the reduced form of IBX, namely,
iodosobenzoic acid (IBA), back to the active I (V) state using
Oxone. We were also aware of the fact that should our
strategy be successful then we could potentially use the
nonexplosive IBA as a precursor to catalytic IBX. Better
yet, we could use commercially available 2-iodobenzoic acid
2
IBAcid as precursors to catalytic amounts of IBX needed
for oxidation reactions.
(2IBAcid), the ultimate precursor for IBX and IBA, as our
Our attention was then turned to identify the optimum
molar ratios of IBX (or IBA or 2IBAcid) and Oxone required
to effect quantitative conversion of primary alcohols to the
corresponding carboxylic acids. Table 1 lists our optimization
results from such an investigation. We reasoned that potas-
catalytic reagent. Preliminary results of these successful
strategies are reported herein.
Our initial effort was directed at identifying a suitable
aqueous solvent system in which the organic substrate could
be oxidized using IBX and in which the reduced form of
IBX could be reoxidized to its active state using Oxone.
1
0
sium persulfate present in Oxone is the active oxidant
responsible for the (re)oxidation of IBA and 2IBAcid to IBX,
as well as for the oxidation of the initially formed aldehyde
to carboxylic acid. The theoretical yield of carboxylic acid,
calculated on the basis of the total availability of oxidants
and its consumption in each reaction, is given in parantheses
in the yield column in Table 1. A cursory evaluation of the
summarized results reveals that the two instances where
appreciable amounts of aldehyde product is observed is when
the molar amount of Oxone present is less than the amount
of IBX present in the reaction mixture. Though we have not
investigated this optimization study in greater detail and at
the rigorous exclusion of oxygen, these preliminary results
are an indication that the Oxone-facilitated reoxidation of
IBA back to IBX is likely faster than the oxidation of
aldehyde to carboxylic acid by the same reagent. This
3-Phenyl-1-propanol was chosen as a protypical substrate
for this optimization, as well as other optimization studies
reported in this paper. Oxidation reactions were attempted
in aqueous mixtures of THF and acetonitrile. Aqueous mix-
tures of acetone were not included in this study for fear of
complications from in situ generated dioxirane as an alternate
and potential oxidant in the reaction medium.12 Reactions
(
6) (a) M uˆ lbaier, M.; Giannis, A. Angew. Chem., Int. Ed. 2001, 40, 4393-
4
4
394. (b) Sorg, G.; Mengel, A.; Jung, G. Angew. Chem., Int. Ed. 2001, 39,
395-4397.
(
7) Ozanne, A.; Pouys e´ gu, L.; Depernet, D.; Fran c¸ ois, B.; Quideau, S.
Org. Lett. 2003, 5, 2903-2906.
8) Thottumkara, A. P.; Vinod, T. K. Tetrahedron Lett 2002, 43, 569-
72.
(
5
(
9) Moore, J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001-3003.
(10) Oxone is commercially available from Aldrich Chemical Co. and
is a 2:1:1 molar mixture of KHSO5, KHSO4, and K2SO4. For the use of
Oxone in the oxidation of 2-iodobenzoic acid to IBX, see: Frigerio, M.;
Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537-4538.
(12) Webb, K. S.; Ruszkay, S. J. Tetrahedron 1998, 54, 401-410.
(13) Travis, B. R.; Sivakumar, M.; Hollist, G. O.; Borhan, B. Org. Lett.
2003, 5, 1031-1034.
(
11) Bunton, C. A.; Foroudian, H. J.; Gillitt, N. D. J. Phys. Org. Chem.
1
999, 12, 758-764.
2934
Org. Lett., Vol. 7, No. 14, 2005

Table 1. Efficiency of Oxone as a Co-oxidanta
Table 2. Scope of Substrates
reagent
equiv)
Oxone
(equiv)
yield, %
(R ) OH)
yield, %
(R ) H)
(
b
IBX, 0.2
IBX, 0.3
IBX, 0.3
IBX, 0.5
IBX, 0.6
IBX, 0.3
0.3
0.65
1.5
0.4
0.3
0.9
0.8
1.15
26 (40)
trace
trace
trace
28
b
62 (70)
b
93 (100)
b
50 (65)
b
63 (75)
18
b
80 (90)
trace
trace
trace
b
2
2
IBAcid, 0.2
IBAcid, 0.3
52 (70)
b
92 (100)
a
All reactions were carried out at 1.5 mmol scale at 70 °C for 6h.
Theoretical yield of acid based on the total consumption of available
b
oxidants are given in parenthesis.
conclusion is based on the fact that the Oxone present in
the reaction medium can only effect the oxidation of
aldehydes to acids and IBA (or 2IBAcid) to IBX and cannot
oxidize primary alcohols to carboxylic acids (vide supra).
Therefore, once all of the Oxone present in the reaction
medium is consumed, the only oxidation that can occur is
the selective oxidation of the primary alcohol to the aldehyde
by the regenerated IBX, resulting in the isolation of the
aldehyde product. This optimization study clearly indicated
to us that commercially available and less expensive 2IBAcid
can be successfully used as a precursor for IBX in these
oxidation reactions. The scope and viability of using 2IBAcid
as a precursor to the required catalytic amount of IBX is
demonstrated through efficient oxidation of several primary
and secondary alcohols (vide infra).
Table 2 lists a variety of alcohols, both primary and
secondary, oxidized by the catalytic use of in situ generated
IBX in the presence of Oxone. Several salient features of
the protocol are readily apparent. The use of 2IBAcid in
catalytic amounts and the use of aqueous mixtures of organic
solvents as the reaction medium are both desirable goals of
eco-friendly approaches to carrying out chemical transforma-
tions. The protocol is widely applicable and tolerates the
presence of a wide range of substituents on substrates (entries
2IBAcid along with 2.8 equiv of Oxone, clearly indicating
a promise for achieving an acceptable turnover number for
the present catalyst system.
4, 6-8, and 13). Oxidation of both primary and secondary
(14) General Procedure for Oxidation of Alcohols. To a solution of
alcohols occurs in good to excellent yields. While primary
alcohols are cleanly oxidized to the corresponding carboxylic
acids, oxidations of secondary alcohols to ketones are not
complicated by the undesired accompaniment of Bayer-
Villiger oxidation of ketones due to the presence of Oxone
in the reaction. Oxidation of vicinal alcohol (entry 14) does
not result in the cleavage of the C-C bond, and a sensitive
group such as a cyclopropyl moiety survives the reaction
conditions (entry 13). Also noteworthy is the fact that the
oxidation of 5-hexene-1-ol cleanly provided the correspond-
ing acid without affecting and/or oxidatively transforming
the double bond. The oxidation of 1,10-decanediol to sebacic
acid in 97% yield was achieved using only 0.4 equiv of
the alcohol substrate (1.5 mmol) in acetonitrile/water (20 mL, 2:1 v/v) was
added the required amount of the catalytic oxidant (IBX, IBA, or 2IBAcid)
and the required amount of Oxone (see text). The mixture was then
maintained at 70 °C for 6 h and subsequently cooled in an ice bath to
completely precipitate the insoluble hypervalent iodine byproduct, which
was then removed by filtration. The precipitate was successively washed
with water (2 × 10 mL) and dichloromethane (2 × 10 mL), and the
combined filtrate was subsequently extracted with dichloromethane (2 ×
2
0 mL). The organic extract was then treated as follows depending on
whether a primary or secondary alcohol was being oxidized. The organic
extract obtained from the workup of a primary alcohol oxidation reaction
was dried (MgSO4) and evaporated to yield the carboxylic acid product,
sometimes contaminated with ca. 2-5% of 2-iodobenzoic acid derivatives,
requiring column chromatographic purification. The organic extract obtained
from the oxidation of secondary alcohols was subsequently washed with
aqueous sodium bicarbonate (15% solution, 30 mL) to remove the acidic
impurities, dried (MgSO4), and evaporated to yield ketones in essentially
pure form.
Org. Lett., Vol. 7, No. 14, 2005
2935

We anticipate that the simplicity and catalytic nature of
the system, the recyclability of the catalyst, and the use of
aqueous solvent systems as the reaction medium will make
the protocol appealing to synthetic chemists, especially to
Research Council of Western Illinois University for providing
a SEED grant to initiate this study.
Supporting Information Available: Experimental pro-
1
4
1
those practicing greener approches to synthetic chemistry.
cedures and characterization data and copies of H NMR
spectra of selected products that are not commercially
available. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. The authors gratefully acknowledge
the National Science Foundation (CHE-0412614) for support
of this research. The authors also thank the University
OL050875O
2936
Org. Lett., Vol. 7, No. 14, 2005