Wet Silica-Supported Permanganate for
the Cleavage of Semicarbazones and
Phenylhydrazones under Solvent-Free
Abdol R. Hajipour,*,†,‡Hadi Adibi,†and
Arnold E. Ruoho‡
Pharmaceutical Research Laboratory, College of Chemistry,
Isfahan University of Technology, Isfahan 84156, Iran, and
Department of Pharmacology, University of Wisconsin,
Medical School, 1300 University Avenue, Madison,
Received February 19, 2003
Abstract: Wet silica-supported potassium permanganate
was used as an inexpensive and efficient reagent for conver-
sion of semicarbazones and phenylhydrazones to the corre-
sponding carbonyl compounds under solid-state conditions.
Hydrazine derivatives of carbonyl compounds are
highly crystalline and are used for the characterization
and purification of carbonyl compounds.1Since, the
regeneration of carbonyl compounds under mild condi-
tions is important, extensive studies on the cleavage of
these derivatives to the parent carbonyl compounds have
been carried out.2-8
Over the last 2 decades, the use of solid supports has
become popular due to their characteristic properties
such as enhanced selectivity and reactivity, straightfor-
ward workup procedure, milder reaction conditions, and
associated ease of manipulation.9Adsorption of potas-
sium permanganate10on the surface of solid supports
changes the selectivity and reactivity in various reac-
tions.11We previously reported potassium permanganate
supported on alumina for the oxidation of urazoles to
triazolinediones,12aoxidation of alcohols to aldehydes and
ketones under solvent-free conditions,12boxidation of
sulfides and thiols to sulfoxides and disulfides,12cthe
oxidative deprotection of trimethylsilyl and tetrahydro-
pyranyl ethers and of ethylene acetals to the correspond-
ing carbonyl compounds,12dand conversion of oximes to
carbonyl compounds under solid-state conditions.12eThere
has also been increasing interest in reactions that
proceed in the absence of solvent.13,14We now report
potassium permanganate supported on wet silica gel as
an inexpensive, selective, and efficient reagent for the
oxidative cleavage of semicarbazones 1a-q and phenyl-
hydrazones 1r-y to the corresponding carbonyl com-
pounds 2a-y under solvent-free conditions.
The oxidative cleavage of 3-methoxybenzaldehyde semi-
carbazone 1d as a model compound with potassium
permanganate failed in the absence of the supporting
agent, even upon grinding for a prolonged period of time.
The reaction carried out in the presence of dry alumina
and silica gel indicated that wet silica gel is the most
effective. Dry silica gel required longer time and gave
lower yield (60%) whereas the yield of 2d increased to
91% in the presence of premoistened reagent. The
optimum molar ratio of substrate to oxidant (1:3) was
determined for complete conversion of semicarbazones
1a-q and phenylhydrazones 1r-y to the corresponding
carbonyl compounds 2a-y while the reaction was incom-
plete with lesser amounts of reagent (i.e., 1:1, 1:2, and
1:2.5). The mechanism of the reaction and the role of wet
silica gel are not clear for us at this stage.
In this method, oxidative cleavage is achieved by
grinding a mixture of semicarbazones 1a-q or phenyl-
hydrazones 1r-y (1 mmol) and potassium permanganate
(3 mmol) supported on wet silica gel (3 g) in a mortar
with a pestle under solvent-free conditions at room
temperature. The reaction time is usually short (15-45
min) and isolation of product is straightforward (Table
1 and Scheme 1). It is very important to note that the
procedure is effective for the selective cleavage of semi-
* To whom correspondence should be addressed. Fax: +98(0311)-
†Isfahan University of Technology.
‡University of Wisconsin, Medical School.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991.
(2) Curini, M.; Rosati, O.; Pisani, E.; Costantino, U. Synlett 1996,
(3) (a) Mohammadpoor-Baltork, I.; Pourshirvani, Sh. Synth. Com-
mun. 1996, 26, 1. (b) Mohammadpoor-Baltork, I.; Hajipour, A. R.;
Haddadi, R. J. Chem. Res., Synop. 1999, 102. (c) Hajipour, A. R.;
Mohammadpoor-Baltork, I.; Kianfar, G. Bull. Chem. Soc. Jpn. 1998,
71, 2655. (d) Hajipour, A. R.; Mahboubkhah, N. Org. Prep. Proced. Int.
1999, 31, 112. (e) Hajipour, A. R.; Mohammadpoor-Baltork, I.; Niknam,
K. Org. Prep. Proced. Int. 1999, 31, 335.
(4) (a) Firouzabadi, H.; Seddighi, M.; Ahmadi, Z. A.; Sardarian, A.
R. Synth. Commun. 1989, 19, 3385. (b) Hajipour, A. R.; Mallakpour,
S. E.; Mohammadpoor, B. I.; Adibi, H. Monatsh. Chem. B 2003, 134,
45. (c) Shirini, F.; Zolfigol, M. A.; Mallakpour, B.; Mallakpour, S. E.;
Hajipour, A. R. Tetrahedron Lett. 2002, 438, 1555. (d) Hajipour, A. R.;
Mallakpour, S. E.; Baltork, I. M.; Adibi, H. Synth. Commun. 2001, 31,
3409. (e) Hajipour, A. R.; Mallakpour, S. E.; Baltork, I. M.; Khoee, S.
Synth. Commun. 2001, 31, 1187.
(5) Ranu, B. C.; Sarkar, D. C. J. Org. Chem. 1988, 53, 878.
(6) Chakrabarty, M.; Khasnobis, S. Synth. Commun. 1998, 28, 1361.
(7) Varma, R. S.; Meshram, H. M. Tetrahedron Lett. 1997, 38, 7973.
(8) (a) Zhang, G. S.; Gong, H. Synth. Commun. 1999, 29, 2591. (b)
Zhang, G. S.; Gong, H.; Yang, D. H.; Chen, M. F. Synth. Commun.
1999, 29, 1165.
(9) Smith, K., Ed. Solid Supports and Catalysts in Organic Synthe-
sis; Prentice Hall: New York, 1992.
(10) Lee, D. G. Encyclopedia of Reagents for Organic Synthesis;
Paquette, L. A., Ed.; Wiley: New York, 1995.
(11) (a) Noureldin, N. A.; Lee, D. G. Tetrahedron Lett. 1981, 22, 4889.
(b) Zhao, D.; Lee, D. G. Synthesis 1994, 915. (c) Fatiadi, A. J. Synthesis
1987, 85. (d) Sreekumar, R.; Padmakumar, R. Tetrahedron Lett. 1997,
(12) (a) Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. Indian J. Chem.
2002, 41B, 2425. (b) Hajipour, A. R.; Mallakpour, S. E.; Imanzadeh,
Gh. Chem. Lett. 1999, 99. (c) Hajipour, A. R.; Mallakpour, S. E.; Adibi,
H. Sulfur Lett. 2002, 25, 155. (d) Hajipour, A. R.; Mallakpour, S. E.;
Mohammadpoor-Baltork I.; Backnezhad, H. Synth. Commun. 2002, 32,
771. (e) Hajipour, A. R.; Mallakpour, S. E.; Imanzadeh, Gh. Asian
Chem. Lett. 1999, 1.
(13) (a) Toda, F. Acc. Chem. Res. 1995, 28, 480. (b) Toda, F.; Tanaka,
K. Chem. Rev. 2000, 100, 1025.
(14) (a) Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. Chem. Lett.
2000, 460. (b) Hajipour, A. R.; Mallakpour, S. E.; Adibi, H. Chem. Lett.
2001, 164. (c) Hajipour, A. R.; Mallakpour, S. E.; Khoee, S. Chem. Lett.
2000, 120. (d) Hajipour, A. R.; Mallakpour, S. E.; Mohammadpoor-
Baltork, I.; Adibi, H. Synth. Commun. 2001, 31, 1625. (e) Hajipour, A.
R.; Mallakpour, S. E.; Imanzadeh, Gh. Indian J. Chem. 2001, 40B,
237. (f) Hajipour, A. R.; Mallakpour, S. E.; Khoee, S. Synlett 2000, 740.
(g) Hajipour, A. R.; Mallakpour, S. E.; Najafi A. R.; Mazlumi, Gh. Sulfur
Lett. 2000, 24, 137. (h) Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J.
Org. Chem. 2002, 67, 8622.
10.1021/jo034217y CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/02/2003
J. Org. Chem. 2003, 68, 4553-4555
KMnO4/Wet SiO2under Solvent-Free Conditionsa
Conversion of Semicarbazones 1a-q and Phenylhydrazones 1r-y to the Carbonyl Compounds 2 Using
aConfirmed by comparison with authentic samples (IR, TLC. and1H NMR).2-8,15-17
noted.cYield of isolated pure product after purification.dPhenylhydrazones (X ) PhNH).
bSemicarbazones (X ) NHCONH2) unless otherwise
4554 J. Org. Chem., Vol. 68, No. 11, 2003
carbazones of complex molecules such as sterically hin-
dered camphor 1n and menthon 1o. Other derivatives
bearing acid-sensitive as well as base-sensitive functional
groups such as t-butoxycarbonyl group 1p, tetrahydro-
pyranyl ether 1q, and aliphatic or aromatic hydroxy
groups 1v-1y remain intact under the reaction condi-
tions. Interestingly, the R,?-unsaturated derivatives such
as cinnamaldehyde semicarbazone 1e underwent oxida-
tive cleavage very efficiently without affecting the CdC
bond. Cleavage of thiochroman-4-one derivative 1m to
2m is readily carried out without oxidation of the sulfide
group. However, the oxidative cleavage of 2,4-dinitro-
phenylhydrazones and azines failed by this method. As
is shown in Table 1 the substitution on R1and R2does
not effect the yield of products. However this method will
only work when X ) NHPh or NHCONH2. Therefore this
methodology offers a simple, inexpensive, and selective
route for converting semicarbazones and phenylhydra-
zones to the corresponding carbonyl compounds.
In conclusion, it is important to note that this simple
and easy method under solid-state conditions offers
carbonyl compounds from their derivatives in a shorter
reaction period using wet silica-supported potassium
permanganate. Moreover, the oxidative cleavage of these
derivatives takes place at room temperature in the
absence of solvent. Also, this oxidation system is able to
convert complicated semicarbazones in the presence of
other oxidizable functional groups to parent carbonyl
General Methods. Yields refer to isolated products after
purification. The products were characterized by comparing their
spectral (IR,1H NMR), TLC, and physical data with those of
authentic samples.2-8,15-17All1H NMR spectra were recorded
at 90 and 300 MHz in CDCl3 relative to TMS as an internal
standard. All reactions were carried out under solvent-free
conditions at room temperature. Silica gel 60 (230-400 mesh)
was obtained commercially.
Typical Procedure for Oxidative Cleavage of Semicar-
bazones and Phenylhydrazones. Wet silica gel was prepared
by shaking silica gel (20 g, 230-400 mesh) with distilled water
(5 mL). The reagent was prepared by mixing KMnO4(3 mmol,
0.48 g) with wet silica gel (3 g) using a pestle and mortar until
a fine, homogeneous, and purple powder was obtained. A mixture
of acetophenone semicarbazone 1a (1 mmol, 0.177 g) and
KMnO4/wet SiO2(3 mmol, 3.48 g) was ground with a pestle in
a mortar until TLC showed complete disappearance of starting
material, which required 15 min (Table 1). Cyclohexane (2 × 15
mL) was added to the reaction mixture and after vigorous
stirring was filtered through a sintered glass funnel. The solvent
was then evaporated under vacuum. Acetophenone 2a was
obtained in 90% yield (0.16 g), bp 200-202 °C/760 mmHg (lit.15
bp 202 °C/760 mmHg). In the case of phenylhydrazones 1r-y,
the crude product after evaporation of the solvent was purified
by column chromatography on silica gel using a mixture of
cyclohexane and ethyl acetate as eluent (90:10).
5-Methylfurfural (2l): δ 9.50 (s, 1H), 7.11 (d, J ) 3.5 Hz,
1H), 6.20 (d, J ) 3.5 Hz, 1H), 2.52 (s, 3H); IR (neat) υ 1695 (s),
1585 (s), 1565 (m), 1395 (s), 1197 (s), 1070 (m), 990 (m), 810 (s),
550 (w) cm-1.
Thiochroman-4-one (2m):1H NMR (CDCl3) δ 8.20 (d, 1H),
7.60-7.21 (m, 3H), 2.90 (t, 3H), 2.40 (t, 3H); IR (KBr) υ 3050
(w), 2900 (w), 1690 (s), 1600 (s), 1510 (s), 1220 (m), 720 (s) cm-1.
L-Oxazolidine aldehyde (2p):1H NMR (CDCl3) δ 9.55 (bs,
1H), 3.96-4.00 (m, 1H), 3.91 (dd, J ) 8.8 and 2.8 Hz, 1H), 3.74
(dd, J ) 8.8 and 8.3 Hz, 1H), 1.53 (bs, 3H), 1.40 (bs, 3H), 1.34
(s, 9H); IR (neat) υ 1735, 1700 cm-1.
Acknowledgment. We gratefully acknowledge the
funding support received for this project from the
Isfahan University of Technology (IUT), IR Iran (A. R.
H.), and Grant GM 33138 (A. E. R.) from the National
Institutes of Health.
(15) Dictionary of Organic Compounds, 6th ed.; Chapman and
Hall: London, 1982.
(16) Bose, D. S.; Srinivas, P. Synlett 1998, 977.
(17) Teruo, K.; Aukio, M.; Susumu, E.; Tsuneori, F. Mol. Cryst. Liq.
Cryst. 1985, 130, 231.
J. Org. Chem, Vol. 68, No. 11, 2003 4555