Selective oxidation of benzylic substrates to their corresponding carbonyl compounds with 3,6-Bis(triphenylphosphonium)cyclohexene peroxodisulfate

Article abstract of DOI:10.1081/SCC-120018692

3,6-Bis(triphenylphosphonium)cyclohexene peroxodisulfate (BTPCP) was found to be a highly effective and selective oxidant for the conversion of benzyl monohalides, nitrils, and amines to their corresponding carbonyl compounds under mild and neutral conditions.

Full text of DOI:10.1081/SCC-120018692

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Selective Oxidation of Benzylic Substrates to Their
Corresponding Carbonyl Compounds with 3,6- Bis
(Triphenylphosphonium)cyclohexene Peroxodisulfate
Rashid Badri a & Mousa Soleymani a
a Department of Chemistry , Chamran University , Ahvaz, Iran
Published online: 15 Aug 2006.
To cite this article: Rashid Badri & Mousa Soleymani (2003) Selective Oxidation of Benzylic Substrates to Their Corresponding
Carbonyl Compounds with 3,6- Bis (Triphenylphosphonium)cyclohexene Peroxodisulfate, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:8, 1325-1332, DOI: 10.1081/SCC-120018692
To link to this article: http://dx.doi.org/10.1081/SCC-120018692
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 8, pp. 1325–1332, 2003
Selective Oxidation of Benzylic Substrates to
Their Corresponding Carbonyl Compounds with
3,6-Bis(Triphenylphosphonium)cyclohexene
Peroxodisulfate
*
Rashid Badri and Mousa Soleymani
Department of Chemistry, Chamran University,
Ahvaz, Iran
ABSTRACT
3,6-Bis(triphenylphosphonium)cyclohexene peroxodisulfate (BTPCP)
was found to be a highly effective and selective oxidant for the conver-
sion of benzyl monohalides, nitrils, and amines to their corresponding
carbonyl compounds under mild and neutral conditions.
The applications of radical anion SOꢀ4 ꢁ, because of its high redox
potential, in organic synthesis in the oxidation of different classes of
organic compounds, has been investigated extensively in recent years.[1–5]
*Correspondence: Rashid Badri, Department of Chemistry, Chamran University,
Ahvaz, Iran.
1325
DOI: 10.1081/SCC-120018692
Copyright & 2003 by Marcel Dekker, Inc.
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1326
Badri and Soleymani
The conversion of benzylic substrates to their corresponding carbonyl
compounds is important in organic synthesis. Although hydrolysis of
benzylic a,a–dihalides[6,7] and diacetates[8] have traditionally been utilized
for the preparation of aldehydes, more practical reagents such as: copper
or lead nitrate,[9] hexamethylene tetramine,[10] sodiumsalt of 2-nitro-
[13]
propane,[11] dimethyl sulfoxide,[12] potassiumdichromate,
pyridine-
N-oxide,[14] Pd(PPh3)4,[15] and copper chloride/Kieselguhr,[16] have also
been reported for the transformation of both aliphatic and aromatic mono-
halides to carbonyl compounds. However, all of these reagent systems
suffer fromtheir own limitations and specially exhibit no selectivity
between the halides, except pyridine-N-oxide when used with microwave
irradiation reported to show selectivity towards benzylic halides.[17]
Recently we have reported the synthesis and use of 3,6-bis(triphenyl-
phosphonium) cyclohexene peroxodisulfate (BTPCP) as an efficient and
selective oxidant for the conversion of benzylic alcohols to their corre-
sponding carbonyl compounds in non-aqueous medium.[18] We now wish
to report a selective one-pot oxidative transformation of benzylic halides,
benzyl nitriles and benzyl amines to their corresponding aldehydes and
ketones with BTPCP under neutral conditions (Sch. 1). This method is of
synthetic interest and provides another facile route concerning the oxida-
tion of aromatic halides, nitriles, and amines by peroxodisulfate. To the
best of our knowledge there is no report about the use of peroxodisulfate
anion for the oxidation of benzylic halides, nitriles, and amines.[19]
As shown in Table 1 primary and secondary benzylic halides are
converted to their corresponding aldehydes and ketones in good to
excellent yields (Entries 1–12). Allylic and saturated halides are resistant
towards this transformation and remained intact in the reaction mixture
(Entries 13–15). Under the same reaction conditions benzyl nitriles and
benzyl amines are also transformed to their corresponding aldehydes
in high yields (Entries 16–21). Further oxidation of aldehydes to their
carboxylic acids was not observed. It is noteworthy that since the reaction
medium was almost neutral, so that some sensitive functionality such as
carbon–carbon double bond remained intact (Entries 9 and 10).
Since several reports[20–24] are known in the literature for the conver-
sion of halides to alcohols in aqueous solutions, therefore we suspected
that hydrolysis of benzylic halides to alcohols might happened initially
and then the alcohols oxidized by oxidant to carbonyl compounds.
Investigation of these reports revealed that the hydrolysis of halides to
alcohols were occurred under severe conditions: long reaction times[20,24]
high temperature,[20] conducted the reaction in basic solutions,[20,24] and
presence of a catalyst.[21–23] Though we conducted our reaction under
mild conditions and for a short time, however, in order to eliminate the

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Oxidation of Benzylic Substrates
1327
Scheme 1.
Table 1. Oxidation of benzylic halides, nitriles, and amines to carbonyl
compounds by BTPCP.
Time
(min)
Yield
(%)
Entry
Substrate
Product
1
2
PhCH2Cl
PhCH2Br
23
24
23
45
45
21
22
24
26
27
97
93
85
73
74
95
87
81
51
43
PhCHO
PhCHO
3
o-ClC6H4CH2Cl
p-NO2C6H4CH2Cl
p-NO2C6H4CH2Br
p-MeOC6H4CH2Br
p-ClC6H4CH2Cl
PhCHCl(CH2)2CO2Et
PhCHClCH¼CHCH2Cl
PhCHClCH¼CHCO2Et
o-ClC6H4CHO
p-NO2C6H4CHO
p-NO2C6H4CHO
p-MeOC6H4CHO
p-ClC6H4CHO
PhCO(CH2)2CO2Et
PhCOCH¼CHCH2Cl
PhCOCH¼CHCO2Et
4
5
6
7
8
9
10
11
22
87
12
13
PhCHCl(CH2)3Cl
25
45
76
—
PhCO(CH2)3Cl
—
14
15
16
17
18
19
20
21
CH3(CH2)3Cl
CH2¼CHCH2Cl
PhCH2CN
45
45
30
28
25
25
24
24
—
—
84
76
87
68
71
73
—
—
PhCHO
o-ClC6H4CH2CN
p-MeOC6H4CH2CN
PhCH2NH2
o-ClC6H4CHO
p-MeOC6H4CHO
PhCHO
o-ClC6H4CH2NH2
p-ClC6H4CH2NH2
o-ClC6H4CHO
p-ClC6H4CHO
Yields refer to isolated products. Products were characterized by comparison of
1
their physical data, IR, and H NMR spectra with those of known samples.

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1328
Badri and Soleymani
ambiguity of formation of alcohols during oxidation process, we tried all
the experiments under the same reaction conditions and time in the absence
of oxidant. No conversion of these benzylic substrates to alcohols under
our mild reaction conditions were observed. This evidence clearly rejects
the possible intermediacy of alcohols in the conversion of the oxidation
process. The plausible mechanism might be as outlined in Sch. 2.
The effect of various solvents such as CHCl3 , CCl4, CH2Cl2, DMSO,
DMF, and MeCN were also investigated. The experimental results show that
MeCN is the best choice for this purpose. A variety of benzylic and non-
Scheme 2.

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Oxidation of Benzylic Substrates
1329
benzylic substrates were examined in this process. We observed that, only
benzylic substrates are transfered to their corresponding carbonyl compounds.
In conclusion, our procedure using BTPCP as a mild and stable
oxidant, because of its neutral conditions, easy workup, good to excellent
yields, and chemoselectivity provides an attractive alternate method for
the conversion of primary and secondary benzylic substrates to their
corresponding carbonyl compounds.
EXPERIMENTAL
1H NMR were recorded on a Bruker advance DPX-250 MHz NMR
spectrometer in CDCl3. The IR spectra were recorded on a Shimadzu 470
spectrophotometer (4000–400 cmꢀ1 region). Melting points were measured
on a Mettler FP5 apparatus. TLC accomplished the purity of substrates and
reactions monitored on silica gel plates. All yields refer to isolated products.
General Procedure for the Oxidation of Benzyl Halides,
Nitrils, and Amines
To a solution of substrate (1 mmol) in CH3CN/H2O (5/1: 30 mL) in a
50 mL round-bottomed flask equipped with a condenser and a magnetic
stirrer and under reflux conditions was added 3,6–bis(triphenylphos-
phonium)-cyclohexeneperoxo-disulfate[18] (1 mmol) in small portions
over 21–45 min. The reaction mixture was then stirred magnetically
under reflux conditions for further 5 min. The progress of the reaction
was monitored by TLC. The reaction mixture was cooled to room
temperature and filtered. The solid material was washed with the solvent.
The filtrates were evaporated and the residue was purified on a silica-gel
plates with appropriate eluent (CCl4/EtOAc: 6/1). Pure carbonyl
compounds were obtained in 43–97% yields (Table 1).
Oxidation of Benzyl Chloride: A Typical Procedure for the
Conversion of Halides to Aldehydes with BTPCP
Benzyl chloride (0.63 g, 5 mmol) was dissolved in acetonitril–water
(5/1: 30 mL), in a 50 ml round-bottommed flask equipped with a magnetic
stirrer and a reflux condenser. The solution was brought to reflux and the
oxidant (3.98 g, 5 mmol) was added in small portions over 23 min.
The reaction mixture was then stirred magnetically under reflux condition

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1330
Badri and Soleymani
for further 5 min. The progress of the reaction was monitored by TLC.
The reaction mixture was cooled to room temperature and filtered.
The solid material was washed with ethyl ether (20 mL). The solvent
was evaporated and the crude product was purified by a silica-gel
plate (eluent: CCl4/EtOAC: 6/1). Pure benzaldehyde was obtained in
97% yield.
ACKNOWLEDGMENT
The authors thank Chamran University for financial support of
this work.
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Received in the USA February 17, 2002