2,6-Dicarboxypyridinium fluorochromate-promoted oxidation of alkyl-arenes into carbonyl compounds under nonaqueous and aprotic conditions

Article abstract of DOI:10.1080/00397911.2010.529228

Benzylic C-H oxidation of a wide variety of alkyl- and cycloalkyl arenes employing 2,6-dicarboxypyridinium fluorochromate under mild reaction conditions is described. The corresponding carbonyl compounds are obtained in good to excellent yields. Taylor & Francis Group, LLC.

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2,6-Dicarboxypyridinium
Fluorochromate–Promoted Oxidation of
Alkyl-Arenes into Carbonyl Compounds
Under Nonaqueous and Aprotic
Conditions
Yaghoub Sarrafi a , Mahmood Tajbakhsh a , Rahman Hosseinzadeh a ,
Marzieh Sadatshahabi a & Kamal Alimohammadi a
a Faculty of Chemistry, Mazandaran University, Babolsar, Iran
Accepted author version posted online: 10 Aug 2011.Published
online: 01 Nov 2011.
To cite this article: Yaghoub Sarrafi , Mahmood Tajbakhsh , Rahman Hosseinzadeh , Marzieh
Sadatshahabi & Kamal Alimohammadi (2012): 2,6-Dicarboxypyridinium Fluorochromate–Promoted
Oxidation of Alkyl-Arenes into Carbonyl Compounds Under Nonaqueous and Aprotic Conditions,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 42:5, 678-685
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Synthetic Communications1, 42: 678–685, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.529228
2,6-DICARBOXYPYRIDINIUM FLUOROCHROMATE–
PROMOTED OXIDATION OF ALKYL-ARENES INTO
CARBONYL COMPOUNDS UNDER NONAQUEOUS
AND APROTIC CONDITIONS
Yaghoub Sarrafi, Mahmood Tajbakhsh,
Rahman Hosseinzadeh, Marzieh Sadatshahabi, and
Kamal Alimohammadi
Faculty of Chemistry, Mazandaran University, Babolsar, Iran
GRAPHICAL ABSTRACT
Abstract Benzylic C-H oxidation of a wide variety of alkyl- and cycloalkyl arenes employ-
ing 2,6-dicarboxypyridinium fluorochromate under mild reaction conditions is described.
The corresponding carbonyl compounds are obtained in good to excellent yields.
Keywords Alkyl-arenes; carbonyl compounds; 2,6-dicarboxypyridinium fluorochromate;
oxidation
INTRODUCTION
The introduction of carbonyl functionality at the benzylic position from the
corresponding alkyl-arenes is an important transformation in organic synthesis,[1]
because the carbonyl compounds can serve as valuable building blocks in the manu-
facture of special chemicals in pharmaceutical and agrochemical industries. In
addition, aryl ketones are integral parts of various natural products.[2] In the past
few years, many methods have been devised for introducing a carbonyl moiety at
the benzylic position,[3] for example, pyridinium chlorochromate (PCC),[4] Gif
reagent=picolinic acid,[5] RuCl2 (PPh3)3-t-BuOOH,[6] [Rh2(cap)4],[7] mesoporous
CrMCM-41 molecular sieves,[8] 3,6-bis(triphenylphosphonium) cyclohexene peroxo-
disulfate,[9] and in situ–generated Bi(0) as catalyst along with tert-butyl hydroperox-
ide and picolinic acid.[10] Although all of these methods are effective, some of them
have drawbacks such as lengthy workup procedures, harsh reaction conditions,[10]
Received April 25, 2010.
Address correspondence to Yaghoub Sarrafi, Faculty of Chemistry, Mazandaran University,
Babolsar, Iran. E-mail: ysarrafi@umz.ac.ir
678

OXIDATION OF ALKYL-ARENES
679
Scheme 1.
and requirements for absolutely dry and inert media.[6] Thus, there is still a need to
develop an operationally simple, mild, and useful method.
Herein, we report a convenient method for the oxidation of benzylic hydrocar-
bons to the corresponding carbonyl compounds using 2,6-dicarboxypyridinium
fluorochromate (2,6-DCPFC) at room temperature (Scheme 1).
RESULTS AND DISCUSSION
The use of chromium(VI) reagents having quaternary ammonium ions as
effective oxidizing agents has been reported in organic transformations.[11] Recently
we have noticed that the 2,6-dicarboxypyridinium moiety in chromium(VI) reagents
is very effective in the oxidation of alcohols, silyl and tetrahydropyrane (THP)
ethers,[12a] oxidative deprotection of oximes, phenylhydrazones, and semicarbazones
to carbonyl compounds,[12b,c] deprotection of thioacetals and 1,1-diacetates,[13] oxi-
dation of thiols to disulfides and sulfides to sulfoxides,[14] deprotection of trimethyl-
silyl ethers to their parent aldehydes,[15] and oxidation of alcohols, phenols, and
hydroquinones.[16] As a part of our ongoing program to develop new oxidation
methods, we have used 2,6-DCPFC in the oxidation of benzylic hydrocarbons.
2,6-DCPFC is easily prepared by treatment of aqueous solution of CrO3 and
HF with pyridine 2,6-dicarboxylic acid. It is a stable yellowish solid that can be
stored for months without losing its activity.
In this study, oxidation of different alkyl arenes to the corresponding carbonyl
compounds was investigated. To gain some preliminary information on this syntheti-
cally useful reaction, ethyl benzene was chosen as a model substrate. When a mixture
of 1:1 mol ratio of oxidant to ethyl benzene was stirred in different solvents (Table 1),
after only 7 min was an almost quantitative yield of acetophenone obtained in aceto-
nitrile (Table 1, entry 3). As shown in Table 1, this reaction in other solvents gave
Table 1. Oxidation of ethyl benzene to acetophenone with 2,6-DCPFC in different
solvents at room temperature
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
CH2Cl2
C6H6
90
120
7
70
40
99
60
50
70
30
60
CH3CN
THF
40
90
90
90
90
CHCl3
DMF
DMAC
Acetone
aIsolated yield.

680
Y. SARRAFI ET AL.
Table 2. Oxidation of alkyl-arenes to carbonyl compounds using 2,6-DCPFC in CH3CN at room
temperature
Mp or Bp (ꢀC)
Entry
Substrate
Ph-CH2CH3
Ph-CH2Ph
Producta
Time (min) Yieldb (%) Observed Reported[17]
1
2
7
10
60
55
99, 97c
92
18–20
47–48
20[17a]
49[17a]
3
4
82
104–105
94–95
103–105[17a]
95
95[17a]
5
6
60
55
98
97
81–83
83[17a]
283–285
285[17a]
7
8
9
15
65
15
89
88
76
41–43
38–40
42[17b]
38–41[17a]
178[17a]
175–177
10
11
20
20
70
75
198–200
198–200
200[17a]
199[17a]
(Continued )

OXIDATION OF ALKYL-ARENES
681
Table 2. Continued
Mp or Bp (ꢀC)
Time (min) Yieldb (%) Observed Reported[17]
Entry
Substrate
Producta
12
15
80
202–203
204[17a]
13
14
15
25
60
60
80
20
25
247–250
228–232
66
248[17a]
230[17a]
67[17a]
16
17
60
50
76–77
78[17a]
120
Trace
106[17a]
aAll of the products were characterized by comparison of their spectral and physical data with authentic
samples.
bYields refer to isolated products.
cThe reaction was carried out with 10 mmol of substrates.
less yield of the products in longer reaction time (Table 1, entries 1, 2, and 4–8). An
interesting feature of this procedure is that the reaction could be followed visually.
Completion of the reaction was recognized when the color of the reaction mixture
changed from yellowish to dark green.
To show the generality and applicability of this method, a variety of benzylic
substrates were oxidized under the optimal reaction conditions, and the results are
presented in Table 2.

682
Y. SARRAFI ET AL.
As shown in Table 2, when conducting the oxidation of ethyl benzene on a
10-mmol scale, nearly the same yield of acetophenone as in small-scale reaction
was obtained (Table 2, entry 1). Similarly, diphenyl methane gave 92% yield of ben-
zophenone after 10 min (Table 2, entry 2). Oxidation of benzyl methyl ketone and
benzyl phenyl ketone to afford the corresponding dicarbonyl compounds takes a
longer reaction time (Table 2, enteries 3 and 4). Under the same reaction conditions,
fluorene, anthrone, indan, and indene gave fluorenone, anthraquinone, 1-indanone,
and 2-indene-1-one respectively in good yields (Table 2, entries 5–8). Indan, after
only 15 min, selectively gave a good yield of its mono-oxidized product (Table 2,
entry 7).
2,6-DCPFC can also act as an efficient reagent for the oxidation of methyl ben-
zenes to the corresponding aldehydes. When toluene was treated with 2,6-DCPFC at
room temperature, after about 15 min 76% of benzaldehyde together with a small
amount of benzoic acid formed (Table 2, entry 9). Similarly, xylenes converted selec-
tively to their tolualdehyde derivatives in good yields together with a small amount
of the corresponding toluic acids (Table 2, entries 10–12). p-Methoxytoluene also
gave good yield of p-methoxybenzaldehyde after 25 min (Table 2, entry 13). How-
ever, alkyl arenes with electron-withdrawing groups proceeded to the corresponding
aldehydes in poor yields and long reaction time (Table 2, entries 14–17). For
example, o-bromotoluene or p-nitrotoluene even after 60 and 120 min gave 20%
o-bromobenzaldehyde and a trace amount of p-nitrobenzaldehyde, respectively.
Increasing the amount of reagent and reaction temperature did not improve the yield
of the corresponding aldehydes but led to the formation of the corresponding acid in
poor yields.
To show the advantages and drawbacks of this method, we compared oxi-
dation of diphenylmethane to benzophenone with some other oxidants reported in
the literature in Table 3. As shown in this table, oxidation with 2,6-DCPFC is
Table 3. Oxidation of diphenylmethane to benzophenone by 2,6-DCPFC in comparison with some other
reagents
Entry
Reagent
2,6-DCPFC
2,6-DCPFC
Conditions
CH3CN, rt
Solid phase
Time
Yield (%)
Reference
1
2
3
4
5
6
10 min
1 h
92
14
91
99
90
76
—
—
3b
3c
3d
3e
HBr–H2O2
CrO3-H5IO6
Cr-PILCPa - t-BuOOH
PDCb -t-BuOOH
CH2Cl2, rt
CH3CN, rt
12 h
1 h
CH2Cl2, rt, N2 atm
Substrate–t-BuOOH–
PDC ¼ 1:4:4, benzene, rt
K2CO3, CH2Cl2, rt
Methanol, 80 ꢀC
44 h
14 h
c
Rh2(cap)4 - t-BuOOH
7
8
16 h
12 h
55
53.8
7
8
Mesoporous CrMCM-41,
Molecular Sieves,
H2O2 (50%)
9
t-BuOOH, Catalyst Bi(0),
Picolinic Acid
Pyridine–AcOH (9:1),
100 ꢀC
16 h
95
—
aCr-PILCP: chromium-pillared clay catalyst.
bPDC: pyridinium dichromate.
cRh2(cap)4: dirhodium caprolactamate.

OXIDATION OF ALKYL-ARENES
683
superior to other methods in terms of yields, easier isolation of the products, milder
reaction conditions, and shorter reaction time.
CONCLUSION
In conclusion, oxidation of benzylic C-H in arenes to their carbonyl com-
pounds can be effectively performed with 2,6-DCPFC under mild reaction con-
ditions. Selective oxidation, simple procedure, easy reaction workup, efficiency,
good yields, and short reaction time are the advantages of this method that make this
reagent a useful addition to the category of oxidants for benzylic substrates.
EXPERIMENTAL
All the chemicals were purchased from Merck. The reactions were monitored
by thin-layer chromatography (TLC) using silica-gel plates, and the products were
purified by flash column chromatography on silica gel (Merck, 230–400 mesh) and
were identified by comparison of their spectra (1H NMR and FT-IR) and physical
1
data with those of the authentic samples. H NMR spectra were recorded with
Brucker DRX500 Avance (400-MHz) spectrometers, using CDCl3 as solvent. IR
spectra were recorded on a Pye-Unicam SP 1100 spectrophotometer.
Preparation of 2,6-Dicarboxypyridinium Fluorochromate (2,6-DCPFC)
To a solution of CrO3 (2.00 g, 0.02 mol) in 1.0 cm3 water in a polyethylene bea-
ker, 40% HF (1.5 cm3, 0.03 mol) was added with stirring. An orange-red solution was
obtained. The reaction mixture was then cooled in an ice bath (ꢁ5 ꢀC), and pyridine
2,6-dicarboxylic acid (3.342 g, 0.02 mol) was added portionwise. The orange crystal-
line compound formed that was then filtered under vacuum using a polyethylene
funnel, washed with petroleum ether (3 ꢂ 10 cm3), rapidly dried in a vacuum desica-
tor, and finally stored in a polyethylene bag. The yield of 2,6-DCPFC was found to
be 92% (5.28 g).[12c]
General Procedure for the Oxidation of Benzylic Hydrocarbons
In a round-bottomed flask (50 ml) equipped with a magnetic stirrer, a mixture
of the substrate (1 mmol) in CH3CN (5 cm3) and 2,6-DCPFC (1 mmol) was placed.
The reaction mixture was stirred at room temperature for the specified time (Table 2).
The progress of the reaction was monitored by TLC or visually. After the reaction
was completed, the mixture was filtered, and the solid material was washed with
diethyl ether (2 ꢂ 10 cm3). The combined filtrate was evaporated under reduced
pressure to afford pure carbonyl compound. If necessary, the product was further
purified on a silica-gel plate or silica-gel column with appropriate eluent.
ACKNOWLEDGMENT
Financial support of this work from the Research Council of Mazandaran
University is gratefully acknowledged.

684
Y. SARRAFI ET AL.
REFERENCES
1. (a) Warren, S. Organic Synthesis: The Disconnection Approach; John Wiley and Sons:
Singapore, 2004; p. 57, 201, and 330; (b) Ghosh, S.; Banik, B. K.; Ghatak, U. R. An
expeditious synthesis of 1,2,3,4-tetrahydro-1,1-dimethylphenanthrenes. J. Chem. Soc.,
Perkin Trans. 1. 1991, 3195–3197.
2. Compere, D.; Marazano, C.; Das, B. C. An enantioselective access to lobelia alkaloids.
J. Org. Chem. 1999, 64, 4528–4532.
3. (a) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional Group
Preparations; VCH: New York, 1989; p. 591; (b) Khan, A. T.; Parvin, T.; Choudhury,
L. H.; Ghosh, S. A simple synthetic protocol for oxidation of alkyl arenes into ketones
using a combination of HBr–H2O2. Tetrahedron Lett. 2007, 48, 2271–2274; (c) Yamazaki,
S. Chromium(VI) oxide–catalyzed benzylic oxidation with periodic acid. Org. Lett. 1999,
1, 2129–2132; (d) Choudary, B. M.; Prasad, A. D.; Bhuma, V.; Swapna, V.
Chromium-pillared clay as a catalyst for benzylic oxidation and oxidative deprotection
of benzyl ethers and benzylamines: A simple and convenient procedure. J. Org. Chem.
1992, 57, 5841–5844; (e) Chidambaram, N.; Chandrasekaran, S. tert-Butyl
hydroperoxide-pyridinium dichromate: A convenient reagent system for allylic and
benzylic oxidations. J. Org. Chem. 1987, 52, 5048–5051.
4. Hosseinzadeh, R.; Tajbakhsh, M.; Vahedi, H. Selective oxidation of methylarenes with
pyridinium chlorochromate. Synlett 2005, 2769–2770.
5. Kim, S. S.; Sar, S.; Tamrakar, P. Gif chemistry for oxidation of activated methylenes to
ketones. Bull. Korean Chem. Soc. 2002, 23, 937–938.
6. Murahashi, S. I.; Komiya, N.; Oda, Y.; Kuwabara, T.; Naota, T. Ruthenium-catalyzed
oxidation of alkanes with tert-butyl hydroperoxide and peracetic acid. J. Org. Chem.
2000, 65, 9186–9193.
7. Catino, A. J.; Nichols, J. M.; Choi, H.; Gottipamula, S.; Doyle, M. P. Benzylic oxidation
catalyzed by dirhodium(II, III) caprolactamate. Org. Lett. 2005, 23, 5167–5170.
8. Mohapatra, S. K.; Selvam, P. A highly selective, heterogeneous route to enones from
allylic and benzylic compounds over mesoporous CrMCM-41 molecular sieves. J. Catal.
2007, 249, 394–396.
9. Badri, R.; Soleymani, M. 3,6-Bis(triphenylphosphonium) cyclohexene peroxodisulfate as
an efficient and mild oxidizing agent for conversion of alkylbenzenes to corresponding
carbonyl compounds. Synth. Commun. 2002, 32, 2385–2389.
10. Bonvin, Y.; Callens, E.; Larrosa, I.; Henderson, D. A.; Oldham, J.; Burton, A. J.; Barrett,
A. G. M. Bismuth-catalyzed benzylic oxidations with tert-butyl hydroperoxide. Org. Lett.
2005, 21, 4549–4552.
11. (a) Patel, S.; Mishra, B. K. Chromium(VI) oxidants having quaternary ammonium ions:
Studies on synthetic applications and oxidation kinetics. Tetrahedron 2007, 63, 4367–4406;
(b) Tajbakhsh, M.; Mohammadpoor-Baltork, I.; Alimohammadi, K. An efficient and
selective solid state oxidation of thiols to disulfides with quinolinium fluorochromate on
silica gel. Monatsh Chem. 2003, 134, 1571–1575; (c) Tajbakhsh, M.; Alimohammadi,
K.; Ramzanian Lehmali, F.; Barghamadi, M.; Shakeri, A. Quinolinium fluorochromate:
An efficient and convenient reagent for oxidative cleavage of thioacetals to their parent
carbonyl compounds. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 2587–2591.
12. (a) Tajbakhsh, M.; Hosseinzadeh, R.; Yazdani-Niaki, M. Synthesis and application of
2,6-dicarboxypyridinium chlorochromate as a new oxidizing reagent for alcohols, silyl
ethers, and THP ethers under mild and non-aqueous conditions. J. Chem. Res., Synop.
2002, 508–510; (b) Tajbakhsh, M.; Hosseinzadeh, R.; Yazdani-Niaki, M. 2,6-Dicarboxy-
pyridinium chlorochromate: A mild, efficient, and selective reagent for oxidative deprotec-
tion of oximes to carbonyl compounds. Tetrahedron Lett. 2002, 43, 9413–9415; (c)

OXIDATION OF ALKYL-ARENES
685
Tajbakhsh, M.; Hosseinzadeh, R.; Ramzanian Lehmali, F.; Sadatshahabi, M. 2,6-Dicar-
boxyopyridinium fluorochromate: A mild and efficient reagent for oxidative deprotection
of oximes, phenylhydrazones to their corresponding carbonyl compounds under
solvent-free conditions. J. Chin. Chem. Soc. 2005, 52, 1005–1009.
13. Hosseinzadeh, R.; Tajbakhsh, M.; Shakoori, A. R.; Yazdani-Niaki, M. 2,6-Dicarboxypyr-
idinium chlorochromate: An efficient and selective reagent for the mild deprotection of
acetals, thioacetals, and 1,1-diacetates to carbonyl compounds. Monatsh Chem. 2004,
135, 1243–1249.
14. (a) Tajbakhsh, M.; Hosseinzadeh, R.; Shakoori, A. R. 2,6-Dicarboxypyridinium chloro-
chromate: An efficient and selective reagent for the oxidation of thiols to disulfides and
sulfides to sulfoxides. Tetrahedron Lett. 2004, 45,1889–1893; (b) Tajbakhsh, M.; Moham-
madpoor Baltork, I.; Ramzanian Lehmali, F. Quinulinium fluorochromate
C9H7NHCrO3F: An efficient and convenient reagent for the oxidative deprotection of tri-
methylsilyl ethers in nonaqueous conditions. Phosphorus, Sulfur Silicon Relat. Elem. 2003,
178, 2617–2620; (c) Tajbakhsh, M.; Khazaei, A.; Shabani Mahalli, M.; Ghorbani Vaghi,
R. N,N-Dibromobenzenesulfonamide as a reagent for oxidative cleavage of oximes to
their parent carbonyl compounds under non-aqueous and aprotic conditions. J. Chem.
Res., Synop. 2004, 141–142; (d) Tajbakhsh, M.; Lakouraj, M. M.; Fadavi, A. Allyltriphe-
=
nylphosphonium peroxodisulfate (CH2 CHCH2PPh3)2S2O8: An efficient and convenient
reagent for the oxidation of alcohols, silyl, and THP ethers under nonaqueous conditions.
Synth. Commun. 2004, 34, 1173–1181.
15. Tajbakhsh, M.; Hosseinzadeh, R.; Sadatshahabi, M. 2,6-Dicarboxypyridinium fluoro-
chromate: A mild and efficient reagent for oxidative deprotection of trimethylsilyl ethers
to their corresponding carbonyl compounds. Phosphorus, Sulfur Silicon Relat. Elem. 2005,
180, 2279–2283.
16. Tajbakhsh, M.; Hosseinzadeh, R.; Sadatshahabi, M. Synthesis and application of
2,6-dicarboxypyridinium fluorochromate as a new solid phase oxidant. Synth. Commun.
2005, 35, 1547–1554.
17. (a) Furniss, B. S.; Manaford, A. J.; Rogers, V.; Smith, P. W. G.; Tatchell, A. R. Vogel’s
Textbook of Practical Organic Chemistry, 4th Ed.; 1978; p. 1192, 1196; (b) Shriner, R. L.;
Hermann, C. K. F.; Morrill, T. C.; Curtin, D. Y.; Fuson, R. C. The Systematic
Identification of Organic Compounds; Wiley: New York, 2004; p. 652.