2,6-Dicarboxypyridinium chlorochromate: A mild, efficient, and selective reagent for oxidative deprotection of oximes to carbonyl compounds

Article abstract of DOI:10.1016/S0040-4039(02)02323-7

The use of 2,6-dicarboxypyridinium chlorochromate (2,6-DCPCC) as a new, rapid, efficient, and selective reagent for the oxidative deprotection of oximes to their corresponding carbonyl compounds in acetonitrile at ambient temperature is described.

Full text of DOI:10.1016/S0040-4039(02)02323-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9413–9416
2,6-Dicarboxypyridinium chlorochromate: a mild, efficient, and
selective reagent for oxidative deprotection of oximes to
carbonyl compounds
Rahman Hosseinzadeh,* Mahmood Tajbakhsh* and Mohammad Yazdani Niaki
Department of Chemistry, Mazandaran University, Babolsar, Iran
Received 12 August 2002; revised 1 October 2002; accepted 11 October 2002
Abstract—The use of 2,6-dicarboxypyridinium chlorochromate (2,6-DCPCC) as a new, rapid, efficient, and selective reagent for
the oxidative deprotection of oximes to their corresponding carbonyl compounds in acetonitrile at ambient temperature is
described. © 2002 Elsevier Science Ltd. All rights reserved.
Nitrogen derivatives of aldehydes and ketones such as
oximes are highly crystalline compounds. They consti-
tute a very efficient method for the isolation, purifica-
tion, and characterization of carbonyl compounds.1
Oximes not only serve as protecting groups for car-
bonyl compounds2 but also have other uses such as the
preparation of nitriles,3 amides via Beckmann rear-
rangement,4 or to activate the carbonyl group.5 In
addition, oximes can be prepared from non-carbonyl
compounds6a–c and, therefore, regeneration of carbonyl
compounds from their oximes is an important reaction.
dicarboxypyridinium chlorochromate (2,6-DCPCC) as
a new, rapid and efficient reagent for the oxidative
deprotection of oximes to their carbonyl compounds at
room temperature.
This reagent is easily and cheaply prepared by the
reaction of pyridine 2,6-dicarboxylic acid with
chromium trioxide in 6N hydrochloric acid. 2,6-
DCPCC is soluble in polar solvents such as acetonitrile
and acetone, slightly soluble in THF, chloroform and
dichloromethane and insoluble in benzene, n-hexane
and carbon tetrachloride. This oxidant is stable and can
be stored for months without losing its activity. The pH
of the 0.01 M aqueous solution of this compound is 2.3,
which is less acidic than that reported for the 3-car-
boxypyridinium chlorochromate (2.02)19 and pyri-
dinium chlorochromate (1.75).21 The chromium content
of the reagent was determined by atomic absorption
and the experimental and calculated results are in a
very good agreement.
Some of the methods reported earlier for deoximation
of carbonyl compounds consist of oxidative7 or reduc-
tive methods,8 using for example, trimethylsilyl
chlorochromate,9 titanium silicalite-1,10 dimethyl dioxi-
rane,11 t-butylhydroperoxide,12 o-iodoxybenzoic acid
(IBX),13 manganese triacetate,14 ammonium persul-
phate-silica,15 Dess–Martin periodinane,16 quinolinium
fluorochromate,17 peroxymonosulfate on silica gel,18 3-
carboxypyridinium chlorochromate,19 etc. Some of
these reagents suffer from one or other disadvantages
such as long reaction times, difficulties in isolation of
products, expense and also the potential to cause explo-
sions by excessive heating during preparation.7a,13,14,16a
Moreover, many of the methods cited in the literature
describe the deoximation of aldoximes, which give low
yields of aldehydes as the liberated aldehydes are
overoxidized.8a,20 In this paper we wish to report 2,6-
The results illustrated in Table 1 indicate that the
reaction is successful for a variety of aliphatic and
aromatic oximes (Scheme 1).
It is noteworthy that, unlike other oxidative hydrolytic
methods, the major drawback of over-oxidation of the
aldehydes to their carboxylic acid was not observed.
Interestingly, a,b-unsaturated oximes underwent deoxi-
mation very efficiently without rearrangement of the
CꢀC bond and the reaction is essentially chemoselec-
tive. Furthermore, functional groups such as hydroxy
and methoxy were inert to this reagent and no by-
product formation was observed (Table 1). Deprotec-
Keywords: 2,6-dicarboxypyridinium chlorochromate; deprotection;
oximes; oxidation; carbonyl compounds.
* Corresponding authors. E-mail: rahman@umz.ac.ir
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02323-7

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R. Hosseinzadeh et al. / Tetrahedron Letters 43 (2002) 9413–9416
Table 1. Oxidative deprotection of oximes using 2,6-DCPCC
Entry
Substrate
t (min)
Producta
Yield (%)b
1
2
3
4
5
6
7
8
PhCHꢀNOH
8
12
10
9
20
14
9
PhCHO
94
92
92
94
92
90
95
94
89
87
92
88
89
90
86
80
84
82
4-MeC6H4CHꢀNOH
2-MeOC6H4CHꢀNOH
2-HOC6H4CHꢀNOH
4-NO2C6H4CHꢀNOH
4-BrC6H4CHꢀNOH
C6H5C(CH3)ꢀNOH
(Ph)2CꢀNOH
4-ClC6H4C(CH3)ꢀNOH
3,4-(MeO)2C6H3C(Me)ꢀNOH
4-PhC6H4C(CH3)ꢀNOH
PhCOC(CH3)ꢀNOH
(PhCꢀNOH)2
PhCH(OH)C(Ph)ꢀNOH
CH3COC(CH3)ꢀNOH
PhCHꢀCHCHꢀNOH
Cyclohexanone oxime
Camphor oxime
4-MeC6H4CHO
2-MeOC6H4CHO
2-HOC6H4CHO
4-NO2C6H4CHO
4-BrC6H4CHO
C6H5COCH3
8
(Ph)2CO
9
14
17
12
19
9
22
30
20
30
35
4-ClC6H4COCH3
3,4-(MeO)2C6H3COCH3
4-PhC6H4COCH3
PhCOCOCH3
(PhCO)2
PhCH(OH)COPh
CH3COCOCH3
PhCHꢀCHCHO
Cyclohexanone
Camphor
10
11
12
13
14
15
16
17
18
a All the products were identified by comparing IR, NMR and TLC with those of authentic samples.
b Yield refers to isolated product.
advantage of using this reagent over related com-
pounds as the oxidative deprotecting reagent is illus-
trated in Table 2. We consider that our procedure
represents a useful addition to the array of deoxima-
tion reactions. The oxidizing activity of this reagent is
under further investigation.
Scheme 1.
Preparation of 2,6-DCPCC
tion of aliphatic oximes normally requires longer
reaction times (entries 15–18).
To a solution of 10 g chromium trioxide (0.1 mol) in
18 ml hydrochloric acid (0.11 mol), 16.7 g pyridine-
2,6-dicarboxylic acid (0.1 mol) was added over 5 min
at −5°C. The resulting solution was stirred at −5°C
for 2 h by which time a yellow-orange solid precipi-
tated. The crystals were collected on a sintered glass
funnel and dried in vacuum, yield 24.5 g, 90% (Cr%
calcd 17.13%, found 17.03%).
Another noteworthy advantage of the reagent is the
exclusive oxidation of oximes irrespective of the pres-
ence of semicarbazones or phenylhydrazones. When
mixtures of equimolar amounts of 2-methoxybenz-
aldehyde oxime and 2-methoxybenzaldehyde semicar-
bazone or 2-methoxybenzaldehyde phenylhydrazone
were treated with 2,6-DCPCC, only the oxime was
selectively oxidized to the corresponding carbonyl
compound and the semicarbazone or phenylhydrazone
remained unchanged (Scheme 2).
General procedure for the regeneration of carbonyl
compounds from oximes
Oxidation of semicarbazones or phenylhydrazones
with 2,6-DCPCC requires a higher molar ratio of oxi-
dant, much longer reaction times, reflux temperature
in acetonitrile, and gives low yields.
To a solution of oxime (2 mmol) in acetonitrile (20
ml), 2,6-DCPCC (4 mmol) was added and the mix-
ture was stirred at room temperature. The progress of
the reaction was followed by TLC or GC. The reac-
tion mixture was filtered and the solid material was
washed with acetonitrile (20 ml). Purification of the
crude products using a silica-gel plate or silica-gel
column (eluent: CCl4/Et2O) afforded pure carbonyl
compounds in 80–94% yields.
This reagent has been used for oxidative deprotection
of various oximes to the corresponding carbonyl com-
pounds in acetonitrile at room temperature and is
superior to previously reported methods in terms of
yields, molar ratio, and shorter reaction times. The

R. Hosseinzadeh et al. / Tetrahedron Letters 43 (2002) 9413–9416
9415
Scheme 2.
Table 2. Deprotection of oximes by 2,6-DCPCC in comparison with other reagents
Substrate
Reagent
Ratio of reagent:substrate
Time
Temp.
Yield (%)
Ref.
PhCHꢀNOH
PhC(CH3)ꢀNOH
PhCHꢀNOH
PhC(CH3)ꢀNOH
PhC(CH3)ꢀNOH
PhCHꢀNOH
PhCHꢀNOH
PhCHꢀNOH
PhC(CH3)ꢀNOH
PhC(CH3)ꢀNOH
2,6-DCPCCa
2,6-DCPCCa
3-CPCCb
3-CPCCb
QFCc
2:1
2:1
2:1
2:1
3:1
–
1.5:1
4:1
4:1
2:1
8 min
9 min
1 h
1 h
4–6 h
2 h
0.5 h
20 min
4 h
rt
rt
94
95
85
90
87
56
86
74
92
98
–
–
reflux CH2Cl2
reflux CH2Cl2
reflux CH3CN
rt
40°C
rt
rt
19
19
22
23
24
25
25
26
TEACCd
MCCe/SiO2
PFCf/H2O2
PFCf/H2O2
QDCg
1.25 h
reflux CH3CN
a 2,6-Dicarboxypyridinium chlorochromate.
b 3-Carboxypyridinium chlorochromate.
c Quinolinium fluorochromate.
d Triethylammonium chlorochromate.
e Methylammonium chlorochromate.
f Pyridinium fluorochromate.
g Quinolinium dichromate.
5. Kabalka, G. W.; Pace, R. D.; Wadgaonkar, P. P. Synth.
Commun. 1990, 20, 2453.
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L. H. Nitrosation; Cambridge University Press: Cambridge,
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Financial support of this work from the Research
Council of Mazandaran University is gratefully
acknowledged.
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