A mild, aromatization of cyclic compounds and oxidation of amino groups to carbonyls using o-iodoxybenzoic acid

Article abstract of DOI:10.14233/ajchem.2013.15129

A new, mild and efficient method has been developed for the synthesis of aromatic compounds and some carbonyls via the oxidative aromatization of amino cyclic compound by using hypervalent iodine reagent in DMSO at ambient temperature. The facile synthetic accessibility and it is as mild as non-hazardous nature render o-iodoxybenzoic acid equivalent of Dess-Martin periodinane reagent in organic oxidations.

Full text of DOI:10.14233/ajchem.2013.15129

Asian Journal of Chemistry; Vol. 25, No. 13 (2013), 7649-7650
http://dx.doi.org/10.14233/ajchem.2013.15129
NOTE
A Mild, Aromatization of Cyclic Compounds and Oxidation of
Amino Groups to Carbonyls using o-Iodoxybenzoic acid
1,*
1
1
2
M. KACAN , G. CICEK , H.R.F. KARABULUT and H. OZYILDIRIM
1Department of Chemistry, Faculty of Science, Trakya University, 22030 Edirne, Turkey
2Faculty of Education, Trakya University, 22030 Edirne, Turkey
*Corresponding author: Fax: +90 284 2351198; Tel: +90 532 7071514; E-mail: mesutkacan@trakya.edu.tr
(Received: 11 January 2013; Accepted: 5 July 2013)
AJC-13778
A new, mild and efficient method has been developed for the synthesis of aromatic compounds and some carbonyls via the oxidative
aromatization of amino cyclic compound by using hypervalent iodine reagent in DMSO at ambient temperature. The facile synthetic
accessibility and it is as mild as non-hazardous nature render o-iodoxybenzoic acid equivalent of Dess-Martin periodinane reagent in
organic oxidations.
Key Words: o-Iodoxybenzoic acid, Aromatization, Oxidation, N-Cyclohexylaniline.
The oxidizing reactants and methods are becoming
important key reactions in the organic chemistry, especially
hypervalent iodine compounds which are used as oxidizing
reagents in many organic reactions. o-Iodoxybenzoic acid
(IBX) is a readily available hypervalent iodine (V) compound
first prepared in 18931, but it was not used until the beginning
of the last decade because of its solubility problem in common
organic solvents. Frigerio and Santagostino2 showed for the
first time in 1994 that o-iodoxybenzoic acid can be employed
in DMSO for the conversion of alcohols to the carbonyl
compounds. In the recent years, Nicolau and co-workers have
uncovered a range of transformations mediated by IBX in
DMSO elevated temperature3. In 2003, IBX was used as a
mild, selective and high yielding method for oxidation of
sulfides to sulfoxides in tetraethylammonium bromide (TEAB)
as an IBX activator in a variety of solvents4. In the same year
Nicolau and co-workers5 showed a different side of IBX. It is
a powerful single-electron-transfer (SFT) agent that readily
accepts new heteroatom-based ligands and thus can (1) effect
the oxidation of ketones, aldehydes and sillyl enol ethers to
the corresponding α,β-unsaturated carbonyl compounds (2)
oxidize benzyl positions and (3) facilitate the cyclization of
N-aryl amide, (thio) carbamates and ureas to afford various
heterocyclic and amino sugars6.
oxidation of cyclic compounds converting to the aromatic
compounds. First of all, here-in we report the successful direct
oxidation of multifarious amines to the corresponding imines
and furthermore amides by IBX under mild conditions in range
of yields. Imines and carbonyls are ubiquitous and useful
intermediates within the domain of synthesis, acting as electro-
philic and nucleophilic participants at the reactions. We also
report the amino substituted cyclic compound is converted to
the corresponding amino aromatic compound via a fantastic
mechanistic way.Aromatization of cyclic compounds is always
significant in the organic synthesis and thus many methods
have been developed.
All chemicals and the solvents were purchased from
Aldrich Chemicals and used without further purification. NMR
spectra were recorded on aVarian 300 MHz for 1H and 75 MHz
for 13C in CDCl3 solution.
General procedure: In a flask (250 mL), DMSO (60 mL)
was added dropwise into IBX (24 mmol) for 15 min and then
the solution was stirred for 0.5 h at room temperature. Then
amino compound (diethylamine or cyclohexylamine) (22
mmol) was poured into the mixture and the last mixture was
heated to 45 ºC for 0.5 h. The reaction was monitored with
TLC. To the reaction, mixture Na2S2O3 (30 mL) and ethyl
acetate (30 mL) were added and the mixture was cooled to
5 ºC in 15 min and crystallized iodobenzoic acid was filtered
out. The liquid phase was extracted with alkaline solution three
times and washed with brine and dried with Na2SO4. It was
Though IBX finds widespread use in oxidative transfor-
mations, there are a few reports on IBX-mediated oxidation
of amines. Also there is no available report on IBX mediated

7650 Kacan et al.
Asian J. Chem.
NH
filtrated and solvent was removed under reduced pressure to
give crude products. Column chromatography methods were
used to separate.
NH2
NH2
IBX
+
N-Cyclohexylaniline: 1H NMR (CDCl3) δ 7.25-7.18 (m,
2H, aromatic), 6.56-6.78 (m, 3H, aromatic), 3.48 (br, 1H, NH),
3.29-3.38 (m, 1H, CH), 2.02–2.06 (m, 2H, CH2), 1.60-1.82
(m, 3H, CH2), 1.42-1.06 (m, 5H, CH2). 13C NMR (CDCl3) δ
147.8, 129.9, 116.6, 113.8, 51.0, 33.9, 26.0, 25.8. DEPT: 129.9,
116.6, 113.8 (CH2), 51.0, 33.9, 26.0, 25.8 (CH), GC-MS; (9,19
dk -175 m/z ).
H
NH2
N
O
O
HO
I
N
H
In this context we were pleased to observe as we proceeded
to investigate the potential of IBX in this transformation, that
amine substrate could be smoothly and rapidly oxidized under
mild conditions at different equivalences in a range of yield.
In here, symmetrical secondary amine (diethylamine) was
employed at the 1.1 equivalent of IBX in 0.2-0.5 mmol scale
in DMSO and the smooth reaction was observed and the
expected product was obtained in excellent yield5 (Fig. 1).
O
O
O
OH
OH
H
I
I
N
O
N
O
H
O
H
IBX (1.1 equiv)
DMSO
N
1 h, 25 to 60 o
C
N
O
H
Fig. 1. Reaction of diethylamine with IBX (1.1 equiv.) in DMSO
O
O
OH
I
The same reaction was also run with an excess amount of
(1:4) IBX and product mixtures were obtained (Fig. 2).
I
N
+
N
O
H
+
N
N
IBX (1.4 equiv)
N
DMSO
O
O
O
O
OH
HN
+
I
N
N
+
Fig. 2. Reaction of diethylamine with IBX (1.4 equiv.) in DMSO
Fig. 4. Proposed mechanism
As seen from the above reaction, if there is IBX in the
reaction medium, oxidation would happen until the consum-
ption of IBX. After this reaction we thought that we could
convert the cyclic compound which is includes substituted
amine group (cyclohexylamine) to the aromatic compound
by using an excess amount of IBX (Fig. 3).
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NH
IBX (excess)
NH2
DMSO (%78)
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Fig. 3. Reaction of cyclohexylamine with excess IBX in DMSO
Conclusion
As expected, cyclohexylamine is reacted with the excess
amount of o-iodoxybenzoic acid and N-cyclohexyl aniline was
obtained. We offered the proposed mechanism for this reaction
as shown below (Fig. 4)