2,6-Dicarboxypyridinium fluorochromate: A mild and efficient reagent for oxidative deprotection of oximes, phenylhydrazones, and semicarbazones to their corresponding carbonyl compounds under solvent-free conditions

Article abstract of DOI:10.1002/jccs.200500140

2,6-Dicarboxypyridinium fluorochromate as a new, rapid, and efficient reagent was prepared and used for the oxidative deprotection of oximes, phenylhydrazones, and semicarbazones to their carbonyl analogues under solvent-free conditions at room temperature.

Full text of DOI:10.1002/jccs.200500140

Journal of the Chinese Chemical Society, 2005, 52, 1005-1009
1005
2,6-Dicarboxypyridinium Fluorochromate: A Mild and Efficient Reagent for
Oxidative Deprotection of Oximes, Phenylhydrazones, and
Semicarbazones to their Corresponding Carbonyl Compounds under
Solvent-free Conditions
Mahmood Tajbakhsh,* Rahman Hosseinzadeh,* Farhad Ramzanian-Lahmali, and Marzieh Sadatshahabi
University of Mazandaran, Babolsar, Iran
2,6-Dicarboxypyridinium fluorochromate as a new, rapid, and efficient reagent was prepared and used for
the oxidative deprotection of oximes, phenylhydrazones, and semicarbazones to their carbonyl analogues un-
der solvent-free conditions at room temperature.
Keywords: 2,6-Dicarboxypyridinium fluorochromate; Deprotection; Solvent-free; Oximes;
Phenylhydrazones; Semicarbazones.
INTRODUCTION
lectivities are enhanced without dilution.18
Selective introduction and removal of protecting groups
plays an important role in the total synthesis of complex natu-
ral products.1 Carbonyl compound derivatives such as ox-
imes, phenylhydrazones, and semicarbazones are used not
only for isolation, purification, and characterization2 but also
for protection of carbonyl compounds.1a Consequently, the
regeneration of the parent carbonyl compounds from them is
an important step in the above mentioned applications. De-
veloping an efficient and mild method for the selective cleav-
age of carbon-nitrogen double bond containing derivatives to
afford carbonyl compounds continues to be a significant as-
pect of experimental organic chemistry.
RESULTS AND DISCUSSION
In recent years, we have reported several chromium
(VI) based oxidants for oxidative transformations under non-
aqueous and or solvent-free conditions.19 As a part of our pro-
gram related to developing new oxidation methods, we now
report a new, simple, and general procedure for the cleavage
of carbon-nitrogen double bonds of oximes, phenylhydra-
zones, and semicarbazones using 2,6-dicarboxypyridinium
fluorochromate (2,6-DCPFC) under solvent-free conditions
at room temperature (Scheme I).
Several procedures for generation of carbonyl com-
pounds have been reported.3-13 Although some of the reported
methods are carried out under mild conditions, most of these
methods are often hazardous, expensive, or use not readily
available reagents or reagents which need to be freshly pre-
pared,1a,14 and some of these methods require strong acid me-
dia, strong oxidizing agents, rare reagents, poisonous reagents,
have poor yields or sometimes require long reaction times,
and have tedious workup procedures.15-17
Scheme I
1
R
1
R
2,6-DCPFC
N
X
O
2
2
R
Solvent-free, r.t
R
X= OH, NHPh, NHCONH2
Recently, an area of intense synthetic endeavor has em-
phasized the use and design of reagents without any solvent.
Avoiding organic solvents during the reactions in organic
synthesis leads to a clean, efficient, and economical technol-
ogy. In solid state reactions, work-up is considerably simpli-
fied, cost is reduced, increased amounts of reactants can be
used in the same equipment; reactivities and sometimes se-
This reagent is easily and cheaply prepared from pyri-
dine 2,6-dicarboxylic acid, 40% aq. hydrofluoric acid, and
chromium (VI) oxide in a molar ratio of 1:1.5:1. This com-
pound is non-hygroscopic and air-stable and can be stored in
a polyethylene bag for long periods without decomposition.
It is soluble in polar solvents such as acetonitrile and acetone,
slightly soluble in THF, chloroform, and dichloromethane

1006 J. Chin. Chem. Soc., Vol. 52, No. 5, 2005
Tajbakhsh et al.
and insoluble in benzene, n-hexane, and carbon tetrachloride.
The chromium content of the reagent was determined by
atomic absorption. Elemental analyses (C, H, N) were also
performed and the experimental and calculated results are in
very good agreement.
ture, cheapness and availability of the reagents, short reac-
tion times, and easy work-up.
EXPERIMENTAL SECTION
A wide variety of oximes and phenylhydrazones such
as benzylic, allylic, and aliphatic have been converted to their
corresponding carbonyl compounds using this reagent at
room temperature (Table 1, entries 1-23). This reagent is able
to convert semicarbazones to the corresponding carbonyl
compounds in moderates yields (entries 23-30). It is worth
commenting that chemoselective cleavage of oximes, phen-
ylhydrazones, and semicarbazones was carried out without
interfering with carbon-carbon double bond (entry 13, 24)
under this reaction condition. Furthermore, functional groups
such as chloro, methoxy, nitro, hydroxyl, and alkyl were also
inert to this reagent, and no byproduct formation was ob-
served (entries 3-10). The most remarkable advantage of this
methodology is that no trace of acid was formed owing to
over oxidation of regenerated aldehyde.
The oximes, phenylhydrazones, and semicarbazones
were prepared by standard procedures.20,21 The purity of the
compounds was checked by TLC. IR spectra were deter-
mined on a Shimadzu instrument. 1H NMR spectra were re-
corded with a JNM-Ex 90A (90 MHz) spectrometer. Products
were isolated and their physical data were compared with
those of known samples.
Preparation of 2,6-dicarboxypyridinium fluorochromate
(2,6-DCPFC)
To a solution of 2 g (0.02 mol) of CrO3 in 1.0 mL of wa-
ter in a polyethylene beaker, 1.5 mL (0.03 mol) 40% HF was
added with stirring. An orange red solution was obtained. The
reaction mixture was then cooled in an ice-bath (-5 °C) and
3.342 g (0.02 mol) pyridine 2,6-dicarboxylic acid was added
portion-wise, with stirring. When an orange crystalline com-
pound separated out, this was filtered under vacuum, using a
polyethylene funnel, washed with petroleum ether (3 ´ 10
mL), rapidly dried in a vacuum desicator and finally stored in
a polyethylene bag. The yield of 2,6-DCPFC was 5.28 g
(92%). Analysis: found Cr, 18.09%; C, 29.25%; N, 4.86%; H,
2.03%. C7H6NO4[CrO3F] calculated: Cr, 18.11%; C, 29.28%;
N, 4.88%; H, 2.10%.
Another noteworthy advantage of the reagent is in the
exclusive oxidation of alcohols in the presence of oximes,
semicarbazones or phenylhydrazones. When mixtures of
equimolar amounts of acetophenone oxime and 2-chloroben-
zylalcohol were ground in a mortar at room temperature with
2,6-DCPFC, only 2-chlorobenzylalcohol was selectively oxi-
dized to 2-chlorobenzaldehyde and the oxime remained un-
changed. Similarly, under the same condition, 2-chloroben-
zylalcohol oxidized to 2-chlorobenzaldehyde in the presence
of an equimolar amount of acetophenone semicarbazone
(Scheme II).
Convertion of oximes, phenylhydrazones and semicarba-
zones to the corresponding carbonyl compounds using
2,6-DCPFC under solvent-free conditions
Typical procedure
In conclusion, we have developed an efficient solvent-
free method for regeneration of carbonyl compounds from
their oximes, phenylhydrazones, and semicarbazones. The
method has advantages in terms of yield, heterogeneous na-
A mixture of benzophenone oxime (0.185 g, 1 mmol)
Scheme II
CHO
Cl
CH2OH
Ph
Ph
H3C
2,6-DCPFC
10 min
N
N
OH
OH
+
+
H3C
Cl
unchanged
>90%
CHO
Cl
Ph
Ph
H3C
CH2OH
Cl
2,6-DCPFC
10 min
N
N
N
Ph
N Ph
+
+
H
H
H3C
unchanged
>90%

A Reagent for Oxidative Deprotection was Prepared
J. Chin. Chem. Soc., Vol. 52, No. 5, 2005 1007
Table 1. Oxidative deprotection of oximes, phenylhydrazones, and semicarbazones using 2,6-DCPFC under solvent-free
conditions
m.p. (°C) or b.p. (°C)/Torr
Time
(min)
Yield
(%)a,b
Entry
Substrate
Ph
Oxidant/substrate
Found
Reported22
N
OH
1
2
2:1
2:1
25
20
15
20
95
86
95
90
48-50
48.5-49
Ph
Ph
N
OH
200-203
216-220
78-81/10
202
218
H3C
Ph
N OH
3
4
2:1
3:1
H3CH2C
C N OH
H
79-81/10
N
Cl
5
6
2:1
2:1
10
30
90
96
212-214
70-73
213-214
71
C N OH
H
Cl
C N OH
H
Cl
7
8
Br
C N OH
H
2:1
2:1
15
17
90
90
57-60
59-60
C N OH
H
231-233
230-231
Br
H3C
N
OH
9
2:1
30
85
221-224
222
O
Ph
N OH
10
11
3:1
3:1
15
30
90
93
119-121/10
154-157
131-133/11
154-156
N OH
N
OH
12
3:1
30
85
177-179
179
OH
N
13
14
4:1
2:1
25
15
80
90
56-59
44-47
58
47
Ph
Ph
N N Ph
H
Cl

1008 J. Chin. Chem. Soc., Vol. 52, No. 5, 2005
Tajbakhsh et al.
N N Ph
H
15
16
2:1
3:1
15
25
90
95
57-58
57
Br
Ph
N N Ph
H
118-120
120-121
CH3
OH
N N Ph
H
17
2:1
20
90
195-198
197
N N Ph
H
18
19
20
H3C
MeO
O2N
3:1
2:1
2:1
10
13
20
90
90
88
201-205
246-247
104-106
204-205
248
N N Ph
H
N N Ph
H
106
Ph
Ph
N
21
22
N Ph
H
2:1
3:1
20
20
98
92
48-50
48.5-49
202
Ph
N
N Ph
H
200-203
H3C
N N Ph
H
23
2:1
20
90
212-214
213-214
Cl
H
O
C N N
24
25
26
27
28
2:1
2:1
2:1
2:1
2:1
23
10
15
20
15
90
60
50
70
50
251-254
56-58
252
57
Ph
H
NH2
O
Br
C N N
H
H
NH2
O
Cl
C N N
46-47
47
H
H
NH2
O
HO
C N N
114-116
178-180
115-116
179
H
H
NH2
O
Ph C N N
H
H
NH2
O
C N N
H
H
29
30
2:1
2:1
30
15
20
50
41-43
43-44
NH2
NO2
O
81-83/10
104-105/13
H3C
Ph
N N
NH2
H
a All the products were identified by comparing IR, NMR, and TLC with those of authentic samples.
b Yields refers to isolated product.

A Reagent for Oxidative Deprotection was Prepared
J. Chin. Chem. Soc., Vol. 52, No. 5, 2005 1009
155-157.
and 2,6-DCPFC (2 mmol, 0.574 g) in a mortar was ground for
25 minutes. When TLC showed complete disappearance of
oxime, the residue was then washed with a minimum amount
of diethyl ether. Evaporation of the solvent gives almost pure
benzophenone (0.16 g, 95%). All the products from other re-
actions were identified by IR, 1H NMR, GC, and comparison
with authentic samples.
9. Ganguly, N. C.; Sukai, A. K.; Sripada, D.; Prithwiraj, D.
Synth. Commun. 2001, 31, 1607.
10. Zhang, G. S.; Yang, D. H.; Chen, M. R.; Cai, K. Synth.
Commun. 1998, 28, 607.
11. Ho, T. L.; Jana, G. H. J. Chin. Chem. Soc. 1999, 46, 639-640.
12. Zhang, G. S.; Chai, B. Synth. Commun. 2000, 30, 2513.
13. Bandgar, B. P.; Makone, S. S. J. Chin. Chem. Soc. 2000, 47,
575-577.
14. Bandgar, B. P.; Shaikh, S. I.; Iyyer, S. Synth. Commun. 1996,
26, 1163.
ACKNOWLEDGEMENT
15. Minghu, W.; Guichun, Y.; Zuxing, C. Synth. Commun. 2000,
30, 3127.
16. Ballini, R.; Petrini, M. J. Chem. Soc. Perkin. Trans. 1, 1988,
2563.
Financial support from the research council of Mazan-
daran University is gratefully acknowledged.
17. Ranu, B. C.; Sarkar, D. C. J. Org. Chem. 1988, 53, 878.
18. (a) Shirini, F.; Zolfigol, M. A.; Azadbar, M. R. Synth.
Commun. 2002, 32, 315. (b) Bose, D. S.; Narasaiha, A. V.;
Lakshminarayana, V. Synth. Commun. 2000, 30, 3121.
19. (a) Hosseinzadeh, R.; Tajbakhsh, M.; Shakoori, A.; Niaki,
M. Y. Monatsh. Chem. 2004, 135, 1243. (b) Tajbakhsh, M.;
Hosseinzadeh, R.; Shakoori, A. Tetrahedron Lett. 2004, 45,
1889. (c) Tajbakhsh, M.; Baltork, I. M.; Alimohammadi, S.
K. Indian Journal of Chem. 2003, 2638. (d) Tajbakhsh, M.;
Baltork, I. M.; Lahmali, F. R. Phosphorus, Sulfur, and Sili-
con 2003, 178, 2620. (e) Tajbakhsh, M.; Baltork, I. M.;
Alimohammadi, S. K. Monatsh. Chem. 2003, 134, 1571. (f)
Tajbakhsh, M.; Hosseinzadeh, R.; Niaki, M. Y. J. Chem. Res.
(S) 2002, 508. (g) Hosseinzadeh, R.; Tajbakhsh, M.; Niaki,
M. Y. Tetrahedron Lett. 2002, 43, 9413. (h) Tajbakhsh, M.;
Heravi, M. M.; Mohanazadeh, F.; Sarabi, S.; Ghassemzadeh,
M. Monatsh. Chem. 2001, 132, 1229. (i) Tajbakhsh, M.;
Ghaemi, M.; Sarabi, S.; Ghassemzadeh, M.; Heravi, M. M.
Monatsh. Chem. 2000, 131, 1213.
Received December 27, 2004.
REFERENCES
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Or-
ganic Synthesis; 3nd. Ed.; John Wiley and Sons: New York,
1999. (b) Bandgar, B. P.; Kasture, S. P. J. Chin. Chem. Soc.
2001, 48, 877. (c) Lee, A. S. Y.; Yeh, H. C.; Yeh, M. K. J.
Chin. Chem. Soc. 1995, 42, 919.
2. Cheronis, N. D.; Entrikin, J. B. Identification of Organic
Compounds; Interscience: New York, 1963.
3. Tajbakhsh, M.; Baltork, I. M.; Lahmali, F. R. J. Chem. Res.
(S) 2003, 710.
4. Kuo, Y. H.; Jang, T. L. J. Chin. Chem. Soc. 1991, 38, 203-
205.
5. Sadeghi, M. M.; Baltork, I. M.; Azarm, M.; Mazidi, M. R.
Synth. Commun. 2001, 31, 435.
20. Vogel, A. I. A Text Book of Practical Organic Chemistry;
ELBS, 3rd ed.; Longman: London, 1975.
21. Mino, T.; Masuda, S.; Nishio, M.; Yamashita, M. J. Org.
Chem. 1997, 62, 2633.
22. Buckingham, J.; Donaghy, S. M. Dictionary of Organic
Compounds; 5th ed., New York, 1982.
6. Mirjalili, B. F.; Zolfigol, M. A.; Bamoniri, A.; Zarei, A. J.
Chin. Chem. Soc. 2004, 51, 509-512.
7. Bose, D. S.; Narasaiha, A. V. Synth. Commun. 2000, 30,
1153.
8. Eshghi, H.; Shafieyoon, P. J. Chin. Chem. Soc. 2005, 52,