Efficient deallylation of allyl phenyl ethers by molecular iodine in PEG-400 and their utility for flavone synthesis

Article abstract of DOI:10.1080/00397911.2013.837489

Rapid and efficient deallylation of allyl phenyl ethers by molecular iodine (20 mol%) in polyethylene glycol-400 at 60 °C has been reported. This method has short reaction time, readily available catalyst, and reuse of reaction medium with good yield. The utility of this methodology has been extended to flavone synthesis. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]

Full text of DOI:10.1080/00397911.2013.837489

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Efficient Deallylation of Allyl Phenyl
Ethers by Molecular Iodine in PEG-400
and Their Utility for Flavone Synthesis
Vivek Humne a & Pradeep Lokahnde a
a Center for Advance Studies, Department of Chemistry , University
of Pune , Pune , India
Published online: 24 Feb 2014.
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To cite this article: Vivek Humne & Pradeep Lokahnde (2014) Efficient Deallylation of Allyl
Phenyl Ethers by Molecular Iodine in PEG-400 and Their Utility for Flavone Synthesis, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:7, 929-935, DOI: 10.1080/00397911.2013.837489
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Synthetic Communications1, 44: 929–935, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.837489
EFFICIENT DEALLYLATION OF ALLYL PHENYL ETHERS
BY MOLECULAR IODINE IN PEG-400 AND THEIR
UTILITY FOR FLAVONE SYNTHESIS
Vivek Humne and Pradeep Lokahnde
Center for Advance Studies, Department of Chemistry, University of Pune,
Pune, India
GRAPHICAL ABSTRACT
Abstract Rapid and efficient deallylation of allyl phenyl ethers by molecular iodine
(20 mol%) in polyethylene glycol-400 at 60 ꢀC has been reported. This method has short
reaction time, readily available catalyst, and reuse of reaction medium with good yield.
The utility of this methodology has been extended to flavone synthesis.
[Supplementary materials are available for this article. Go to the publisher’s online edi-
tion of Synthetic Communications1 for the following free supplemental resource(s): Full
experimental and spectral details.]
Keywords Allyl phenyl ether; deallylation; flavones; molecular iodine; PEG-400
INTRODUCTION
Protection and deprotection are the significant processes in organic transform-
ation. Allyl is a commonly used protecting group for various functionalities,
especially phenols, alcohols, acids, and amines.[1] The stability to acidic and basic
conditions, is the most beneficial feature of allyl protection. Allyl protection is useful
in carbohydrate[2] and peptide synthesis[3,4] and in other polyfunctional molecules.[5]
In general, deprotection of allyl group has been carried out by direct cleavage of C-O
bond using transition metals such as palladium,[6] ruthenium(II),[7] iridium(I),[8]
titanium,[9] and zirconium.[10] Other reagents used for deprotection process are
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ),[11] SeO2,[12] and NBS-hv.[13]
Received July 11, 2013.
Address correspondence to Vivek Humne, Department of Chemistry, University of Pune, Pune
411007, India. E-mail: vivekhumne@rediffmail.com
929

930
V. HUMNE AND P. LOKAHNDE
However, these procedures have several drawbacks such as harsh conditions, tox-
icity, use of stoichiometric proportion, and difficulty of loading the catalyst. There-
fore, development of rapid, efficient, and ecofriendly protocol for the cleavage of
allyl group is exceedingly desirable.
Over the past few decades, molecular iodine has been widely used in pharma-
ceutical and organic syntheses because of its inexpensive, nontoxic, and environmen-
tally benign characteristic nature.[14] Recently, polyethylene glycol (PEG) is used as a
green solvent[15] and has many applications, particularly in substitution, oxidation,
and reduction reactions.[16] Many recent reviews cover the application of PEG in
biotechnology and medicine.[17,18] As a part of a continuing effort in our laboratory
to study iodine-mediated transformations,[19,20] we became interested in the possi-
bility of developing a novel and efficient method of deallylation of allyl phenyl ether
by molecular iodine in PEG-400 and the synthetic application is extended to flavone
synthesis.
RESULTS AND DISCUSSION
Deallylation of allyl phenyl ether by molecular iodine in PEG-400 was studied
by taking 1a as a model reaction (Scheme 1). First, substrate 1a was treated with
5 mol% of iodine, and o-deallylated product 2a was obtained in 46% yield with
recovery of starting substrate after 12 h. Subsequent loading of 20 mol% of iodine
reduces reaction time and increases yield (Scheme 1). However, use of 100 mol%
of iodine does not alter the results. Several solvents such as MeOH, dichloromethane
(DCM), dimethylformamide (DMF), and ethylene glycol were examined for best
reaction medium. However, trace amounts of product (18%) were observed in ethyl-
ene glycol after 18 h. After replacing ethylene glycol by PEG-400, o-deallylated pro-
duct isolated with excellent yield. On the basis of this result, we established that
PEG-400 is a good solvent for deallylation.
To understand the role of PEG-400, we performed deallylation of 1a in various
glycols such as triethylene glycol, PEG-600, PEG-4000, PEG- 6000, and PEG-8000
(Table 1). Poor yield (22%) was observed in triethylene glycol. However, as the
molecular weight of PEGs increases (entries 5–7, Table 1), the viscosity increases.
Therefore, temperature of the solvent has been increased to 100 ꢀC for liquefaction
of PEG. Almost the same results have been observed in other PEGs. In general,
PEG formed the complex with the cation, which activates the anion in the same
medium.[21]
To determine the reusability of the solvent, the reaction mixture was extracted
by ethyl acetate. The combine organic layer was dried over anhydrous sodium sulfate
and evaporated. The resulting mother liquor was subjected to vacuum distillation to
Scheme 1. Cleavage of aryl ally ethers.

DEALLYLATION OF ALLYL ETHERS BY IODINE
931
Table 1. Deallylation of 1a in different glycols
Entry
Glycol
Time (h)
Yield (%)a
1
2
3
4
5
6
7
Ethylene glycol
Triethylene glycol
PEG-400
18
16
18
22
96
95
90
90
88
0.25
0.25
0.3
PEG-600
PEG-4000
PEG-6000
PEG-8000
0.3
0.35
aIsolated yields of the products.
remove water and PEG remains in the bottom part of the container. The recovered
PEG was used for five cycles without loss of activity (Table 2). With this result, we
next turned to study the variety of allyl phenyl ethers (Table 3). Substrates having
electron-withdrawing and electron-donating groups were smoothly deallylated.
In this context, cleavage of 20-allyloxy chalcones 3a–e using 20 mol% of iodine
in PEG-400 has been studied. Interestingly, deallylation with oxidative cyclization of
20-allyloxy chalcones was carried out and gave the corresponding flavones in 45 min
(Scheme 2, Table 4). A variety of 20-allyloxy chalcones were studied by molecular
iodine in PEG-400. Surprisingly, chloro-substituted flavone was afforded in shorter
time (Table 4, entries a, b). Gratifyingly, all the corresponding substituted flavones
were obtained in good yield.
The infrared (IR) spectrum of 4a–f shows that the frequency at 1656 cmꢁ1
1
corresponds to the carbonyl group. In the H NMR spectrum, allylic protons and
a double doublet at 6.87 and 7.45 ppm of coupling constant 15.8 Hz regarding the
C-2 and C-3 of chalcone disappeared. The characteristic signal of flavone was
observed at 6.97 ppm due to its C-3 position. Eventually the formation of product
was confirmed by elemental analysis, which was well correlated to calculate the mol-
ecular formula of the product.
In our previous work, we successfully achieved selective o-deallylation by using
a catalytic amount of iodine in PEG-400.[22a] The role of PEG is possibly to form a
complex with the cation, much like crown ether, and these complexes cause the anion
to be activated.[22b] When iodine was employed for the deallylation process, it acti-
=
vates the C C bond of allyl functionality and forms a three-membered iodonium
Table 2. Recycling of PEG-400 on deallylation of 1a with 10 mol% of iodine
as catalyst at room temperature
Run
Yields (%)a
1
2
3
4
5
95
92
90
90
88
aAll reactions were carried out with 1 mmol of substrate.

932
V. HUMNE AND P. LOKAHNDE
Table 3. Deallylation of allyl phenyl ethers using iodine (20 mol%) in PEG-400 at room temperature
Entry
a
Substrate (1a–i)
Product (2a–i)
Yield (%)a,b
96
b
c
92
88
89
d
e
f
92
94
90
g
h
i
95
90
aIsolated yields of the products.
bSpectral data and mp of the products are matches with the authentic sample.
intermediate, which is stabilized by oxygen atoms of PEG. Similar to this, the forma-
tion of flavones proceed first through deallylation[22a] of chalcone, and then oxidative
cyclization is achieved by complex formation of iodine cation stabilized by PEG
(Fig. 1). The color of the solution remains unchanged, which suggested regenerated
iodine.

DEALLYLATION OF ALLYL ETHERS BY IODINE
933
Scheme 2. Synthesis of flavones.
EXPERIMENTAL
All reagents were of commercial quality, and reagent-quality solvents were
1
used without further purification. H and 13C NMR spectra were determined on a
Table 4. Synthesis of flavones through selective deallylation of allyl phenyl ether by molecular iodine
(10 mol%) in PEG-400
Entry
Product (4a–e)
Time (min)
Temperature (ꢀC)
Yield (%)a
a
20
60
92
b
c
20
45
60
91
86
100
d
45
100
87
e
20
60
90
aIsolated yields of the products.

934
V. HUMNE AND P. LOKAHNDE
Figure 1. Plausible reaction pathway for synthesis of flavone.
Varian Mercury 300-MHz Fourier transform (FT) spectrometer. Mass spectra were
obtained on Shimazdu-QP 5050 GC-MS spectrometer. IR spectra (KBr) were
recorded on a Shimadzu FT-IR DR-8001 spectrophotometer. The purity of the com-
pounds was assessed by thin-layer chromatography (TLC) on silica gel 60 F254.
General Procedure for Synthesis of Flavones (4a)
A mixture of 20-allyloxy chalcones 3 (1 mmol) and iodine (20 mol%) in
PEG-400 (10 mL) was stirred at 60 ꢀC for 30–45 min. The reaction mixture was
poured in a cold solution of sodium thiosulfate and extracted by ethyl acetate.
The combined organic layer was dried over anhydrous Na2SO4, evaporated under
vacuum, and purified by column chromatography. The corresponding product was
obtained in 86–92% yield.
6-Chloro-2-(3-methoxy-4-allyloxyphenyl)-4H-chromen-4-one (4a)
IR (KBr): 3648, 3078, 1702, 1645, 1612, 1564, 1445, 1348, 1296, 1245, 1132,
1064, 1005, 929, 864, 818, 756 cmꢁ1 1H NMR (300 MHz, CDCl3): d 8.12 (d,
;
J ¼ 2.1 Hz, 1H), 7.60 (dd, J ¼ 2.7, 2.4 Hz, 1H), 7.49 (d, J ¼ 12.6 Hz, 1H), 7.32 (s,
1H), 6.96 (d, J ¼ 1.4 Hz, 1H), 6.73–6.70 (m, 1H), 6.10–6.13 (m, 1H), 5.88–5.89 (m,
1H), 5.46 (dd, J ¼ 3.3, 10.5 Hz, 2H), 4.69 (d, J ¼ 5.4 Hz, 2H), 3.96 (s, 3H); 13C
NMR (100 MHz, CDCl3): d 180.75, 163.36, 154.85, 154.17, 151.04, 149.33, 133.54,
132.13, 124.88, 124.61, 123.63, 119.77, 119.52, 118.54, 112.61, 108.89, 106.07,
72.68, 56.05; MS(m=z): 342 (Mþion). Anal. calcd. for C19H15ClO4: C, 66.58; H,
4.41; Cl, 10.34. Found: C, 66.63; H, 4.52; Cl, 10.37.
CONCLUSION
In conclusion, a simple and metal-free deallylation of allyl phenyl ethers to
corresponding phenols using 20mol% of iodine in polyethylene glycol-400 has been
reported. The present method does not involve any hazardous organic solvent. The sol-
vent was reusable for a number of times without appreciable loss of activity. Therefore,

DEALLYLATION OF ALLYL ETHERS BY IODINE
935
this procedure could be classified as green protocol. The present methodology
is applied for the synthesis of flavones occurring in natural products and drugs.
SUPPORTING INFORMATION
Full experimental detail and 1H and 13C NMR spectra of all synthesized com-
pounds can be found via the Supplementary Content section of this article’s webpage.
ACKNOWLEDGMENTS
V. T. H. thanks the Counsil of Scientific and Industrial Research, New Delhi,
India, for the award of a fellowship.
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