Highly efficient method for synthesis of benzoquinones using hypervalent iodine(iii) reagent and sodium bisulfate

Article abstract of DOI:10.1080/00397911.2013.804930

A rapid, one-step, novel approach for the conversion of benzamides into benzoquinones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in aqueous acetonitrile at room temperature. The developed protocol is applicable to several types of substituted benzamide derivatives to get the corresponding benzoquinone products. The developed methodology offers mild reaction condition, short reaction time, and moderate to excellent yields. This is one of the most simple and environmentally benign protocols for synthesis of benzamide derivatives.

Full text of DOI:10.1080/00397911.2013.804930

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Highly Efficient Method for Synthesis
of Benzoquinones Using Hypervalent
Iodine(III) Reagent and Sodium Bisulfate
Kulbhushan A. Sasane a & Vikas N. Telvekar a
a Department of Pharmaceutical Sciences and Technology , Institute
of Chemical Technology , Matunga , Mumbai , India
Published online: 27 Dec 2013.
To cite this article: Kulbhushan A. Sasane & Vikas N. Telvekar (2014) Highly Efficient Method for
Synthesis of Benzoquinones Using Hypervalent Iodine(III) Reagent and Sodium Bisulfate, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:4, 468-473, DOI: 10.1080/00397911.2013.804930
To link to this article: http://dx.doi.org/10.1080/00397911.2013.804930
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Synthetic Communications1, 44: 468–473, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.804930
HIGHLY EFFICIENT METHOD FOR SYNTHESIS
OF BENZOQUINONES USING HYPERVALENT
IODINE(III) REAGENT AND SODIUM BISULFATE
Kulbhushan A. Sasane and Vikas N. Telvekar
Department of Pharmaceutical Sciences and Technology,
Institute of Chemical Technology, Matunga, Mumbai, India
GRAPHICAL ABSTRACT
Abstract A rapid, one-step, novel approach for the conversion of benzamides into benzoqui-
nones using (diacetoxyiodo)benzene(III) and sodium bisulfate has been developed in
aqueous acetonitrile at room temperature. The developed protocol is applicable to several
types of substituted benzamide derivatives to get the corresponding benzoquinone products.
The developed methodology offers mild reaction condition, short reaction time, and moder-
ate to excellent yields. This is one of the most simple and environmentally benign protocols
for synthesis of benzamide derivatives.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Benzamides; benzoquinones; hypervalent iodine; sodium bisulfate
INTRODUCTION
Quinones are large class of compounds having rich and interesting chemistry.
Natural products having benzoquinone structures show biologically significant
properties such as cardiovascular, antitumor, antibacterial, antigerminative, and
Received January 9, 2013.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, Istitute of Chemical Technology, Matunga, Mumbai, India. E-mail: vikastelvekar@rediffmail.com
468

SYNTHESIS OF BENZOQUINONES
469
Scheme 1. Some methods for synthesis of benzoquinones.
antiprotozoan activities. Large numbers of chemical derivatives with 1,4-benzoqui-
none as the basic subunit exhibit prominent pharmaceutical applications such as
antibiotic,[1] antitumor,[2] antimalarial,[3] antineoplastic,[4] anticoagulant,[5] and
herbicidal activities.[6]
In general, quinones are being synthesized by oxidation of phenols, 1,4-dihy-
droxybenzenes or hydroquinones, and dimethybenzenes using ceric ammonium
nitrate (CAN),[7] 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ),[8] nitric acid,[9]
salcomine=O2,[10] chromium oxidants,[11] benzene selenic anhydride,[12] silver
oxide,[13] manganese oxide,[14] and NaBrO3 = wetK10
as oxidizing agents. There
[15]
are two reports of the oxidative degradation of p-hydroxybenzamide using Fremy’s
salt, whereas in another method iodobenzene in combination with oxone was used
for synthesis of 1,4-benzoquinone by Hofmann rearrangement from benzamide.[16,17]
These two conversions required longer reaction times and had lower substrate
compatibility, which limit their applications (Scheme 1).
Therefore, there is need to develop dynamic and feasible protocols for the
transformation of benzamide to benzoquinone, which can activate under milder
reaction conditions. Considering these issues, we focused our attention toward the
expansion of a novel protocol for the synthesis of quinone derivatives.
RESULTS AND DISCUSSION
Our research group is mainly working on the hypervalent iodine reagents. Dur-
ing our study we found that (diacetoxyiodo)benzene(III), which is readily available
and frequently used in several oxidative transformations, can be used for the syn-
thesis of quinones from benzamides. Thus for our initial studies, we used benzamide
as a starting material. It was observed that when benzamide oxidized using (diace-
toxyiodo)benzene, a lower yield (15%) of quinone was isolated after long reaction
time in water–acetonitrile (1:1) as a solvent. It was found that during the reaction
many other unidentified by-products were also formed. Further screening of reagent
and reaction conditions revealed that (diacetoxyiodo)benzene in the presence of
sodium bisulfate leads to formation of a single product with good yield within short
reaction time (Scheme 2).
Scheme 2. Benzamide to benzoquinone using (diacetoxyiodo) benzene and sodium bisulfate.

470
K. A. SASANE AND V. N. TELVEKAR
Table 1. Optimization of reagent conditionsa
Entry
DIB (mmol)
NaHSO4 (mmol)
Time (min)
Yield (%)
1
2
3
4
5
5
1
3
5
5
5
6
1
1
1
1
2
2
45
45
45
60
45
45
45
67
85
83
85
82
aReaction conditions: Benzamide (1 mmol) in water–acetonitrile (1:1) as solvent at
room temperature.
It was reported in the literature that the treatment of (diacetoxyiodo)benzene
with sodium bisulfate leads to the formation of reactive hydroxy (phenyl) iodonium
ions,[18]and we thought that reactive hydroxy(phenyl) iodonium ions may accelerate
the formation of quinone from benzamide. Further investigation of reaction found
that 5 equivalents of (diacetoxyiodo)benzene and 1 equivalent of sodium bisulfate
is suitable for conversion of 1 equivalent of benzamide to quinone (Table 1).
Under these reaction conditions various solvent systems were tried, and it was
found that water–acetone–dichloromethane are suitable solvents, but lower yields
were obtained as compaired to the water–acetonitrile (1:1) solvent system.
To study the prospective and general applicability of the developed method-
ology, various benzamides containing different functional groups were investigated,
and results are summarized in Table 2. It was observed that 2-methyl benzamide and
2-chlorobenzamide reacted smoothly to obtained good yield of respective benzoqui-
none derivatives (Table 2, entries 2–4).It is remarkable to mention that in case of
para substituted methoxy, the deprotection followed by oxidation was observed
(Table 2, entry 6), whereas in the case of meta-substituted methoxy no deprotection
was observed (Table 2, entry 5). Similarly para-substituted hydroxy and amino
benzamide converted into benzoquinone (Table 2, entries 7 and 8).
It was observed that para-methyl benzamide and 2,5-dimethyl benzamide gives
substituted products instead of quinone (Table 2, entries 9 and 10). Reaction of ali-
phatic amides does not take place with this reaction system (Table 2, entry 11).
In summary, we developed a new application of (diacetoxyiodo)benzene(III)
and sodium bisulfate system in aqueous acetonitrile for synthesis of benzoquinones-
from corresponding benzamides. The advantages of the present method are use of
simple shelf reagents, mild reaction conditions, and good yields.
General Procedure for Synthesis of Benzoquinone Derivatives
(Table 2, Entry 1)
(Diacetoxyiodo) benzene (5 mmol, 1.61 g) and NaHSO4ÁH2O (1 mmol, 0.138 g)
were stirred for 10–15 min at room temperature in aqueous solution of acetonitrile
(5 ml water and 5 ml acetonitrile). In this reaction mixture benzamide (1 mmol)
was added and stirring was continuing until reaction went to completion, as moni-
tored by thin-layer chromatography (TLC). After completion of the reaction, the
reaction mixture was quenched with water and further extracted with chloroform

SYNTHESIS OF BENZOQUINONES
471
Table 2. Reaction of amides using (diacetoxyiodo) benzene and sodium sulfatea
Entry
1
Substrate
Productb
Time (min)
Yield (%)c
30
80
2
3
35
40
85
78
4
5
40
40
85
72
6
7
8
40
45
45
75
70
71
9
45
45
70
10
78
(Continued )

472
K. A. SASANE AND V. N. TELVEKAR
Table 2. Continued
Entry
11
Substrate
Productb
Time (min)
24 hrs
Yield (%)c
—
No reaction
aReaction conditions: amides (1 mmol), (diacetoxyiodo)benzene (5 mmol), sodium bisulfate (1 mmol) in
aqueous acetonitrile (10 mL) at room temperature.
bProducts were characterized using 1H NMR, IR, and mp=bp and compared with literature data.
cIsolated yields of pure products.
(3 Â 10 ml). The combined chloroform layers were washed with water (3 Â 20 ml),
dried over Na2SO4, and concentrated on a rota-evaporator to get the crude residue.
The residue was further purified by column chromatography on silica gel using ethyl
aceate–hexane (1:9) as an eluent to afford pure benzoquinone.
1,4-Benzoquinone (Table 2, Entry 1)
1
Mp 115 ꢀC (lit.[19] mp 112 ꢀC); H NMR (60 MHz, CDCl3): 7.59–7.68 (s, 4H);
IR (KBr, cmÀ1): 3165, 3070, 1665, 1589, 1312, 1264, 897.
SUPPORTING INFORMATION
Full experimental detail, 1H NMR, IR and MP=BP can be found via the Sup-
plementary Content section of this article’s Web page.
ACKNOWLEDGMENT
K. A. S. is thankful to the Council of Scientific and Industrial Research (New
Delhi) for the award of a Senior research fellowhip and financial support.
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