Rapid and selective deallylation of allyl ethers and esters using iodine in polyethylene glycol-400

Article abstract of DOI:10.1039/c1gc15153c

A simple and selective deallylation of allyl ethers and esters using iodine (10 mol%) in polyethylene glycol-400 as a green reaction solvent is described. The reaction was performed at room temperature with various aryl/alkyl allyl ethers and esters in go

Full text of DOI:10.1039/c1gc15153c

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COMMUNICATION
Rapid and selective deallylation of allyl ethers and esters using iodine in
polyethylene glycol-400†
Shankaraiah G. Konda, Vivek T. Humne and Pradeep D. Lokhande
Received 9th February 2011, Accepted 15th June 2011
DOI: 10.1039/c1gc15153c
A simple and selective deallylation of allyl ethers and esters
using iodine (10 mol%) in polyethylene glycol-400 as a green
reaction solvent is described. The reaction was performed
at room temperature with various aryl/alkyl allyl ethers and
esters in good to excellent yields. The present methodology
includes inexpensive catalyst, easy work-up, benign reaction
conditions and high selectivity.
the compounds were immediately oxidised to flavones. The
deprotection of allyl carboxylic esters to corresponding acids15b
under similar conditions is reported. The use of DMSO at
higher temperature during reaction, get decomposed and some
other functional groups are oxidized. To avoid the requirement
of higher temperatures, herein we wish to report a selective
deallylation of aryl/alkyl allyl ethers in presence of N-allyl ethers
using iodine (10 mol%) in polyethylene glycol (PEG-400) as the
green reaction solvent.
Introduction
Protection and deprotection of organic functional groups is
of great importance in organic synthesis.1 Allyl groups are
widely used in organic synthesis as versatile protecting groups
of alcohols, amines, and acids due to their availability and to the
stability of the corresponding allyl derivatives. Allyl protecting
groups were also found to be very useful in both carbohydrates2
and peptide synthesis.3,4 The deprotection of allyl ethers using
transition metal catalysts such as palladium,5 ruthenium(II),6
iridium(I),7 titanium8 and zirconium9 are reported. The reported
procedures have limited scope, are expensive and difficult to
loading of catalyst. Development of deprotection methods
under mild condition with high selectivity is desired.
Results and discussion
Our initial studies started with deallylation of aryl allyl ether
1a (entry 1, Table 1) using 10 mol% of iodine and polyethy-
lene glycol-400 as the reaction solvent at room temperature
(Scheme 1, Table 1). The reaction was completed within 20 min
as confirmed by TLC. The reaction mixture was poured into a
beaker containing sodium thiosulphate solution and extracted
with ethyl acetate. The corresponding deallylated product was
obtained in 94% yield. The N-allyl protecting groups remain
constant in the product.
Recently, polyethylene glycol (PEG) has been found to be an
interesting green solvent system.10 the use of PEG as an environ-
mentally benign protocol has proved to have many applications11
particularly, in substitution, oxidation and reduction reactions.
A number of recent reviews have also covered PEG chemistry
and its applications in biotechnology and medicine.12,13 The use
of molecular iodine in organic synthesis has been explored.
In recent years, molecular iodine has received considerable
attention as an inexpensive, non-toxic, readily available catalyst
for various organic transformations under mild and convenient
conditions to afford the corresponding products in excellent
yields with selectivity.14
Scheme 1 Selective deallylation of aryl allyl ethers.
In order to establish the best reaction medium, we performed
the reaction using substrate1a as the modelreaction with various
solvents such as MeOH, DCM, DMF, DMSO, ethylene glycol
and PEG-400 at room temperature; the results are summarized
in Table 2. Using ethylene glycol as the solvent gave very low yield
(28%) of product after 16 h (Table 2, entry 5). No other solvent
effect was observed on the deallylation process. By this result, we
established the polyethylene glycol-400 is a best reaction solvent
for this condition. To understand the role of PEG as a reaction
medium, we also performed the deallylation of same substrate in
EG, TEG and other glycols such as PEG-600, PEG-4000, PEG-
6000 and PEG-8000 (Table 2). In ethylene glycol and triethylne
glycol, the product was observed in low yield (28 and 24%).
Previously, we reported the deprotection of 2¢-allyloxy chal-
cones to flavones15a using iodine–DMSO at 130 ◦C in excellent
yields. The deprotection products were not isolated, since
Organic Research Laboratory, Department of Chemistry, University of
Pune, Pune, 411007, (M.S), India. E-mail: kondasg@rediffmail.com;
Fax: +9120 25691728; Tel: +9120 25896199
† Electronic supplementary information (ESI) available: Characteriza-
tion data of deallylated compounds. See DOI: 10.1039/c1gc15153c
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Table 1 Deallylation of aryl allyl ethers using iodine (10 mol%) in PEG-400 at room temperature
Entry
1
Substrate (1a–h)
Product (2a–h)
Time (min)
20
Yield (%)a,b
94
2
15
92
3
4
18
20
90
88
5
6
15
16
90
90
7
8
18
15
89
92
a Isolated yields of the products. b Products are characterized by spectral analysis.
However, as the molecular weight of PEGs increases (Table 2,
entries-9–11), the viscosity increases. Because of this reason we
raised the temperature up to 70 ◦C to liquefy the PEG. Even so,
no other co-solvents are used.
and acetyl groups at room temperature in good to excellent
yields. We next examined the deprotection of alkyl allyl ethers
in the presence of N-allyl protection (Scheme 2) under similar
conditions, where the reactions take 45–55 min for completion
(Table 3). As additional mol% of iodine was increased, a change
in reaction time or yields of the products was not observed.
Next, we investigated the amount of iodine required to
catalyze the dellylation of substrate 1a (entry 1, Table 1).
Decreasing the catalyst to 5 mol% of iodine afforded the product
in 52% after 5 h with regeneration of substrate. When increased
to 20 mol% of iodine, the product yield was slightly improved
to 96% after 20 min at same reaction conditions. We then used
30 mol% of iodine to catalyze the reaction, but no significant
change in yield and reaction time was observed. Therefore,
the best results were obtained with the use of 10 mol% of
iodine. With this result, we next turned to a variety of aryl allyl
ether substituents (Table 1), which were successfully deallylated
with variety of functionalities including benzyl, PMB, methoxy
Scheme 2 Selective deallylation of alkyl allyl ethers.
In order to evaluate the possibility of applying this methodol-
ogy on a large scale, we carried out the deallyllation of 10 mmol
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Table 2 Effect of solvents on the deallylation of 1a with 10 mol% of
iodine as the catalyst at room temperature
Table 4 Recycling of PEG-400 on deallylation of 1a with 10 mol% of
iodine as catalyst at room temperature
Entry
Solvent
Time (hr)
Yield (%)a
Run
1
92
2
90
3
90
4
88
5
85
Yield (%)a,b
1
2
3
4
5
6
7
8
MeOH
DCM
DMF
DMSO
Ethylene glycol
Triethylene glycol
PEG-400
PEG-600
PEG-4000
PEG-6000
PEG-8000
24
24
24
24
16
12
0.20
0.25
0.40
0.40
0.35
—
—
—
—
28
24
94
94
86
85
86
a All reactions were carried out with 1 mmol of substrate. b Isolated yield.
was not observed. Similarly, tetraalkylammonium iodide did
not give the expected product. On the basis of results and
literatures,17 a tentative mechanism for deallylation is proposed
(Fig. 1). As soon as iodine was added, which activates the C
C
9
10
11
bond and forms a three membered iodonium intermediate, it
is stabilized by interaction with oxygen atom of PEG. The
color of the solution remains unchanged, which supports the
regeneration iodine. The formation of allyl alcohol could not
be traced in the reaction. Finally, we thought that PEG is not
only acting as an efficient solvent system but also acting as PTC;
cause the anion to be activated.
a Isolated yield.
of substrate 1a with 10 mole% of iodine in polyethylene glycol-
400 (100 mL) at room temperature. The yield of corresponding
deallylated product was almost the same as that obtained in the
small scale (~94%).
To determine the reusability of the solvent, the reaction
mixture was extracted with ethyl acetate. The combined organic
layer was dried over anhydrous sodium sulphate and solvent
was evaporated. The remaining mother liquor was subjected to
vacuum distillation to remove water leaving PEG behind in the
container. The recovered PEG was subjected to charge same
substrate for several times (five times) without loss of its activity
(Table 4).
Fig. 1 A proposed mechanism for deallylation of allyl ether using
iodine in PEG.
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.16 In addition, no need of any external Phase Transfer
Catalyst (PTC) or acidic medium to activate the oxygen atom of
ally ether. Initially, we assumed that the deallylation mechanism
is based on the iodine cation, which is stabilized by interaction
with PEG oxygen. However, when potassium iodide or sodium
iodide was employed in the reaction, the deallylation product
Further, we extended our study towards the selective deallyla-
tion of aryl/alkyl esters at room temperature. The corresponding
deallylated products were obtained in good yields (75–82%)
using 10 mol% of iodine in PEG-400 as reaction solvent
(Scheme 3). With this chemoselective deallylation of N-allyl
protected allyl carboxylic esters, we generalized with various
aliphatic and aromatic substrates. The results are summarized
in Table 5.
Table 3 Deallylation of alkyl allyl ethers using iodine (10 mol%) in PEG-400 at room temperature
Entry
1
Substrate (3a–c)
Product (4a–c)
Time (min)
50
Yield (%)a,b
78
2
3
55
45
72
76
a Isolated yields of the products. b Products are characterized by spectral analysis.
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Table 5 Deallylation of aryl/alkyl allyl esters using iodine (10 mol%) in PEG-400 at room temperature
Entry
1
Substrate (5a–d)
Product (6a–d)
Time (min)
25
Yield (%)a,b
82
2
3
35
40
80
76
4
35
78
a Isolated yields of the products. b Products are characterized by spectral analysis.
or esters (1 mmol) in polyethylene glycol-400 (10 mL) was
added iodine (10 mol%) and the reaction mixture was stirred
at room temperature for time period as shown in mentioned
in the corresponding Table. After completion of the reaction
(monitored by TLC), the reaction mixture was poured into a
beaker containing aqueous sodium thiosulphate solution and
extracted with ethyl acetate. The corresponding deallylated
product was obtained in good to excellent yield.
To reuse the solvent, the reaction mixture was extracted
with ethyl acetate. The combined organic layer was dried over
anhydrous sodium sulphate and the solvent was evaporated. The
remaining mother liquor was subjected to vacuum distillation to
remove water leaving PEG in the bottom part of the container.
The recovered PEG was subjected to charge the same substrate
for five times without loss of its activity.
Scheme 3 Selective deallylation of aryl/alkyl allyl esters.
Conclusion
In summary, we have demonstrated a simple and selective
deallylation of aryl/alkyl allyl ethers and esters using 10 mol%
of iodine in polyethylene glycol-400 as a green reaction solvent
at room temperature. The present methodology is applied to
substrates having benzyl, PMB, methoxy and acetyl groups.
Highly selective deallylation of O-aryl/alkyl allyl ethers and es-
ters was observed in presence of N-allyl protection. Advantages
of this protocol include easy of work-up, readily available and
inexpensive catalyst, high yields and benign reaction conditions.
Spectral data of selected deallylated compounds
2-{(N-Allyl-4-chlorophenyl amino) methyl)} phenol (2b). IR
(KBr): 3212, 3056: 1H NMR (300 MHz, CDCl3): d 4.65 (m, 2H),
d 5.26 (m, 1H), d 5.31 (s, 2H, CH2), d 5.94 (m, 1H), d 6.15 (m,
1H), d 6.61–7.28 (m, 8H, Ar-H), d 9.81 (s, 1H, OH); 13H CMR
(300 MHz, CDCl3): 50, 58, 115 (2 ¥ C), 117, 119, 121, 123, 127,
128, 129 (2 ¥ C), 130,135, 147, 158; MS(m/z): 273 (M+ ion),
275 (M+2); Anal. calcd for C16H16NOCl: C, 70.21; H, 5.89; N,
5.12%. Found: C, 70.12; H, 5.96; N, 5.18%
Experimental
Merck, pre-coated silica gel 60 F254 (Aluminum sheets) plates
were used for analytical TLC. IR spectra were recorded (in KBr
pallets) on Shimadzu spectrophotometer. 1H NMR spectra were
recorded (in CDCl3) on Varian Mercury 300 MHz spectrometer
using TMS as an internal standard. The mass spectra were
recorded on Shimazdu- QP 5050 GC-MS spectrometer.
3-(N-Allyl-N-m-tolylamino)-1,3-diphenyl propan-1-ol (4b).
1
IR (KBr): 3198; 3072: H NMR (300 MHz, CDCl3): d 2.24
General experimental procedure for deallylation
(s, 3H, CH3), d 3.48 (m, 1H), d 4.13 (m, 1H), d 4.21 (s, 1H, OH),
d 4.56 (m, 2H), d 5.01 (m, 1H), d 5.26 (m, 1H), d 5.94 (m, 1H),
d 6.41 (m, 1H), d 6.86–7.41 (m, 14H, Ar-H); MS(m/z): 357 (M+
Allylic substrates were prepared by the conventional method
(allyl bromide, K2CO3, DMF) To a solution of allyl ethers
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ion); Anal. calcd for C25H27NO: C, 83.98; H, 7.61; N, 3.92%.
Found: C, 83.87; H, 7.66; N, 3.98%
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Acknowledgements
SGK is thankful to Dr D. S. Kothari Post Doctoral Fellowship
[F.4-2/2006(BSR)/13-301/2008(BSR)], UGC-New Delhi for fi-
nancial support. Authors are thankful to Dr Bhaskar S. Dawane
for his strong support and encouragement. Authors are also
acknowledged to Garware Research Centre, Pune for spectral
analysis.
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