A green procedure for the protection of carbonyl compounds catalyzed by iodine in ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2008.09.088

Aldehydes and ketones are protected with ethylene glycol in the presence of a catalytic amount of iodine in PEG ionic liquid (IL 400) under mild conditions to afford the corresponding ketals in good yields. The recovery of iodine is facilitated by the ionic liquid. The recovered catalyst was reused six times with consistent activity.

Full text of DOI:10.1016/j.tetlet.2008.09.088

Tetrahedron Letters 49 (2008) 7110–7112
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A green procedure for the protection of carbonyl compounds
catalyzed by iodine in ionic liquid
Yi-Ming Ren, Chun Cai *
Chemical Engineering College, Nanjing University of Science & Technology, Nanjing 210094, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 June 2008
Revised 5 September 2008
Accepted 16 September 2008
Available online 19 September 2008
Aldehydes and ketones are protected with ethylene glycol in the presence of a catalytic amount of iodine
in PEG ionic liquid (IL 400) under mild conditions to afford the corresponding ketals in good yields. The
recovery of iodine is facilitated by the ionic liquid. The recovered catalyst was reused six times with
consistent activity.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Molecular iodine
Ionic liquid
Carbonyl compounds
Recyclable
Protection
The protection of carbonyl groups plays an important role in or-
ganic synthesis as well as in the chemistry of drug design. In gen-
However, the reuse of iodine was also difficult. So simple, efficient
supports for reusable iodine are still desirable.
1
eral, this aim could be achieved via the formation of ketals in the
presence of protonic acids, Lewis acids, and a number of transi-
tional metal complexes including Rh, Pd, and Pt as catalysts. How-
ever, most of the traditional processes suffer from a variety of
disadvantages, such as pollution, use of noble metals and expen-
sive reagents, high temperature, stoichiometric amounts of
reagent, and tedious work-up procedures. Therefore, the develop-
ment of a catalytic system that may be stable, easily separable,
and reusable has been long awaited.
Room-temperature ionic liquids have been emerging as promis-
ing green solvents for the past decade. Their nonvolatile nature
5
2
gives them significant advantage in minimizing solvent consump-
tion. Their polarity renders them good solvents for various organic,
inorganic, and polymeric compounds, and therefore good media for
5
b
homogeneous reactions. Because of their unique solubility prop-
erties, that is, miscibility gap between water and organic solvents,
they have become interesting candidates for separation processes
by simple liquid–liquid extraction with either aqueous or conven-
6
In recent years, the usage of molecular iodine has drawn consid-
erable attention as an inexpensive, nontoxic, and readily available
catalyst for various organic transformations to afford the corre-
sponding products in excellent yields with high selectivity. The
mild Lewis acidity associated with iodine enhances its usage in or-
ganic synthesis to realize several organic transformations using
tional organic solvents. Furthermore, ionic liquids are found to be
an efficient reaction media for the immobilization of transition me-
7
tal-based catalysts, Lewis acids, and enzymes. Now, we synthesize
8
,10
novel PEG ionic liquids (Scheme 1),
the ionic liquids and toluene
have the advantages of both homogeneous and heterogeneous
phase at different temperatures (biphasic conditions at lower tem-
peratures and monophasic at higher temperatures) with the ease
of product as well as catalyst separation. Herein, we present the
preparation of 1,3-dioxolanes using a catalytic amount of iodine
in the PEG ionic liquid (IL 400) under mild conditions with good
yields (Scheme 2).
3
stoichiometric levels to catalytic amounts. However, the reuse of
iodine is difficult because it has a good solubility in most organic
solvents and easy sublimation at high temperature. Previously,
the iodine supported on polyvinylpyrrolidone (I
propyl silica gel (I
or natural phosphate (I
2
/PVP),4a amino-
/APSG),4b neutral alumina surface (I
4c,d
2
2 2 3
/Al O ),
/NP)4e had been reported for some reac-
2
tions. The above supports were the preferred choice as supports
to keep the reaction medium under mild and neutral conditions.
H C
3
CH3
N
N
PEG
N
N
2
2OSO CH3
*
Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
Scheme 1. PEG ionic liquids.
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.088

Y.-M. Ren, C. Cai / Tetrahedron Letters 49 (2008) 7110–7112
7111
Table 2
O
11
HO
HO
Protection of carbonyl compounds as ketals using iodine as catalyst in IL 400
I2 / IL 400
rt.
O
R
O
+
Entry
Carbonyl compounds
Yielda (%)
R
R1
R1
1
2
3
4
5
6
7
8
9
Benzaldehyde
83
72
75
80
95
96
60
56
58
96
94
93
Scheme 2.
4-Nitro-benzaldehyde
4-Chloro-benzaldehyde
4-Methoxy-benzaldehyde
Butanal
Propanal
Acetophenone
2-Hydroxy-acetophenone
4-Methoxy-acetophenone
Cyclohexanone
4-Methyl-cyclohexanone
Cyclopentane
First, the addition of molecular iodine (25 mg) to a mixture of IL
00 (1 mL) and toluene (1 mL). The mixture was stirred at 80 °C for
several minutes. After the mixture was cooled to room tempera-
ture, we found that most of iodine was dissolved in IL 400
Fig. 1). The light yellow of toluene was changed to light lavender
after the toluene was washed with water (1 mL). Then the titration
was processed by adding to toluene standard Na solution. It
4
10
11
12
(
2 2 3
S O
a
Isolated yields.
only has about 0.1 mg iodine in the toluene. The result shows that
the iodine can be excellently distributed in the IL 400.
Next, the condensation of benzaldehyde and ethylene glycol
using molecular iodine as catalyst was examined with several
PEG ionic liquids at room temperature, and the results are summa-
rized in Table 1. According to Banik’s previously reported reaction
Table 3
Reusing of iodine immobilized in IL 400
Yielda (%)
Run
conditions using molecular iodine,9 the appreciable amount of I
2
1
2
3
4
5
6
7
83
83
82
83
82
81
65
was 5 mol % to benzaldehyde, and the reaction time was 16 h in
the present reaction. As shown in Table 1, IL 400 was more satisfied
to obtain excellent yield (entry 3) than other PEG ionic liquids. The
PEG with larger molecular weight, such as PEG 2000 and PEG 4000,
was not a good choice, because the IL 2000 and IL 4000 remain in
the solid state at room temperature which had to have a high reac-
tion temperature for the stir. However, a low yield was obtained
without iodine or ionic liquid (entries 1 and 3). So, the IL 400
was chosen as reaction medium for the reaction.
a
Isolated yields.
Several carbonyl compounds had been used as substrates to re-
act with ethylene glycol in the system of iodine immobilized in the
IL 400, and the results are shown in Table 2. It was shown that both
aldehydes and ketones were converted to the corresponding 1,3-
dioxolanes in good yields. However, the reaction of aliphatic car-
bonyl compounds under the same conditions gave the correspond-
ing products in higher yields than aromatic carbonyl compounds,
because the conjugation effect in aromatic carbonyl compounds in-
duced by the direct connection to the aromatic rings made the car-
bonyl group less positive and therefore, reduced its activity in
nucleophilic addition reaction.
The recycling performance of iodine immobilized in the IL 400
was investigated in the reaction of benzaldehyde and ethylene gly-
col. The data listed in Table 3 show that I
six times with consistent activity.
2
/IL 400 could be reused
In conclusion, we have developed a simple, inexpensive, and
effective method for the protection of carbonyl compounds cata-
lyzed by iodine in ionic liquid. The advantages of the present reac-
tion are the elimination of the metals, and toxic reagents,
operational simplicity and good yields of products. Moreover, the
simple experimental procedure being combined with ease of
recovery and reuse of iodine is expected to contribute to the devel-
opment of a green strategy for the other iodine-catalyzed reaction.
Further studies on the reuse of iodine are now in progress.
Figure 1. Photographic plates. (1) toluene: 1 mL; (2) IL 400: 1 mL; (3) 1 mL toluene
and 1 mL IL 400 at 80 °C; (4) 25 mg iodine in 1 mL toluene; (5) 25 mg iodine in a
mixture of IL 400 (1 mL) and toluene (1 mL), the upper layer was toluene; (6) the
toluene of photo 5 was washed with 1 mL water, the upper layer was toluene.
Acknowledgments
We are grateful to Professor Chunxu Lü for supporting the
synthetic method of ionic liquids. We are also grateful to Nanjing
University of Science and Technology for financial support.
Table 1
Effect of ionic liquids on the reaction of benzaldehyde and ethylene glycol
Entry
IL
Yielda (%)
References and notes
1
2
3
—
IL 200
IL 400
709
80
1
.
Greene, T. W. Protective Groups in Organic Synthesis; Springer: Berlin, 1981; pp
29–133.
1
83
b
2. (a) Kocienski, P. J. Protecting Groups, Thieme 1994, 156–170; (b) Cooks, R. G.;
Chen, H.; Eberlin, M. N.; Zheng, X.; Tao, W. A. Chem. Rev. 2006, 106, 188; (c)
Hoffman, R. V. Tetrahedron Lett. 1974, 15, 2415; (d) Lipschutz, B. H.; Pollart, D.;
Monforte, J.; Kotsuki, H. Tetrahedron Lett. 1985, 26, 705; (e) Zhu, Z.; Espenson, J.
H. Organometallics 1997, 16, 3658; (f) Ott, J.; Ramos Tombo, G. M.; Schmid, B.;
25
4
IL 1000
79
a
Isolated yields.
Without iodine.
b

7
112
Y.-M. Ren, C. Cai / Tetrahedron Letters 49 (2008) 7110–7112
Venanzi, L. M.; Wang, G.; Ward, T. R. Tetrahedron Lett. 1989, 30, 6151; (g) Wang,
B.; Gu, Y.; Song, G.; Yang, T.; Yang, L.; Suo, J. J. Mol. Catal. A: Chem. 2005, 233,
21; (h) Clerici, A.; Pastori, N.; Porta, O. Tetrahedron Lett. 2001, 57, 217.
(a) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2002,
3, 9703; (b) Bandgar, B. P.; Shaikh, K. A. Tetrahedron Lett. 2003, 44, 1959; (c)
Phukan, P. J. Org. Chem. 2004, 69, 4005; (d) Phukan, P. Tetrahedron Lett. 2004, 45,
reduced pressure gave the desired pure product IL 400 in 86% yield. 1H NMR
(500 MHz, CDCl ): 2.85 (s, 6H, 2OSO CH ), 3.75 (t, 36H, J = 4.3 Hz
(OCH CH ), 3.88 (s, 6H, 2NCH ), 7.48 (s, 2H, 2CH), 7.60 (s, 2H, 2CH), 8.92 (s,
2H, 2CH); C NMR (500 MHz, CDCl ): d 37.1, 39.5, 49.5, 69.1, 70.3, 70.4, 122.8,
3
d
2
3
1
2
2
)
n
3
1
3
3
.
3
2
+
2+
2+
4
123.6, 137.1; ESI-MS: 294.12, M /2, n = 9, 316.42, M /2, n = 10, 338.13, M /2,
+ 2+
n = 11, 360.33, M2 /2, n = 12, 382.13, M /2, n = 13, 108.9 (95); IR (KBr, cm ):
À1
4
2
785; (e) Banik, B. K.; Fernandez, M.; Alvarez, C. Tetrahedron Lett. 2005, 46,
479; (f) Hessian, K. O.; Flynn, B. L. Org. Lett. 2006, 8, 243; (g) Ishihara, M.; Togo,
3445, 3182, 2985, 1456, 1321, 1194, 1101, 1059, 895, 594.
The spectra data for IL 200: 1H NMR (500 MHz, CDCl
3
) d 2.84 (s, 6H, 2OSO
2 3
CH ),
H. Tetrahedron 2007, 643, 1474; (h) Rao, W.; Tay, A. H. L.; Goh, P. J.; Choy, J. M.
L.; Ke, J. K.; Chan, P. W. H. Tetrahedron Lett. 2008, 49, 122; (i) Ren, Y. M.; Cai, C.
Catal. Lett. 2007, 118, 134; (j) Ren, Y. M.; Cai, C. Catal. Commun. 2008, 9, 1017.
(a) Iranpoor, N.; Tamami, B.; Niknam, K. Can. J. Chem. 1997, 75, 1913; (b)
Tamami, B.; Iranpoor, N.; Mahdavi, H. Synth. Commun. 2002, 32, 1251; (c) Deka,
N.; Sarma, J. C. Chem. Lett. 2001, 794; (d) Saxena, I.; Borah, D. C.; Sarma, J. C.
Tetrahedron Lett. 2005, 46, 1159; (e) Zahouily, M. Z.; Mezdar, A.; Rakik, J.;
Elmakssoudi, A.; Rayadh, A.; Sebti, S. J. Mol. Catal. A: Chem. 2005, 233, 43.
(a) Welton, T. Chem. Rev. 1999, 99, 2071; (b) Wasserscheid, P.; Keim, W. Angew.
Chem., Int. Ed. 2000, 39, 3772.
3.70 (t, 17H, J = 8.0 Hz (OCH
2
CH
2
)
n
), 3.94 (s, 6H, 2NCH ), 7.52 (s, 2H, 2CH), 7.58
3
2
+
2+
(s, 2H, 2CH), 8.78 (s, 2H, 2CH); ESI-MS: 184.22, M /2, n = 4, 206.12, M /2,
n = 5, 228.31, M2 /2, n = 6, 250.11, M /2, n = 7, 272.23, M /2, n = 8, 83.14
+
2+
2+
À1
4
.
(100); IR (KBr, cm ): 3454, 3153, 2985, 1435, 1350, 1207, 1051, 858, 623.
The spectra data for IL 1000: 1
H
NMR (500 MHz, CDCl
), 3.70–3.76 (m, 97H, J = 15.0 Hz (OCH CH ), 3.82 (s, 6H, 2NCH
7.52 (s, 2H, 2CH), 7.59 (s, 2H, 2CH), 8.81 (s, 2H, 2CH); ESI-MS: 448.17, M /2,
d
2.85 (s, 6H,
3
)
2OSO
2
CH
3
2
)
2 n
3
),
2+
2+
2+
2+
n = 16), 470.20, M /2, n = 17, 492.20, M /2, n = 18, 514.27, M /2, n = 19,
+
2+
2+
2+
5
6
7
.
.
.
558.27, M2 /2, n = 21, 580.30, M /2, n = 22, 602.33, M /2, n = 23, 624.36, M
/
2+ 2+ 2+
2, n = 24, 646.36, M /2, n = 25, 668.37, M /2, n = 26, 690.43, M /2, n = 27,
712.43, M2 /2, n = 28, 153.07 (100); IR (KBr, cm ): 3447, 3153, 2985, 1447,
+
À1
Huddleston, J. G.; Willauer, H. D.; Swatloski, R. P.; Visser, A. E.; Rogers, R. D. J.
Chem. Soc., Chem. Commun. 1998, 1765.
(a) Sheldon, R. J. Chem. Soc., Chem. Commun. 2001, 2399; (b) Gordon, C. M. Appl.
Catal., A 2001, 222, 101; (c) Zimmermann, H. E.; Wang, P. A. J. Am. Chem. Soc.
1352, 1205, 1117, 1060, 858, 587.
11. Typical procedure for the protection of carbonyl groups catalyzed by iodine
immobilized in the IL 400: To a solution of carbonyl compounds (1 mmol) and
1
993, 115, 2205.
2
ethylene glycol (1 mL) in IL 400 (1 mL) was added I (0.05 mmol). The mixture
8
9
.
.
Zhi, H. Z.; Luo, J.; Ma, W.; Lü, C. X. Chem. J. Chin. Univ. 2008, 29, 772.
Banik, B. K.; Chapa, M.; Marquez, J.; Cardona, M. Tetrahedron Lett. 2005, 46,
was stirred at room temperature. After the reaction, toluene (2 Â 1 mL) was
added to the mixture. The mixture was stirred at 80 °C for several minutes.
After the mixture was cooled to room temperature, the upper toluene
containing the expected product was separated by decantation. The toluene
was evaporated, and the pure products were obtained by purification through
basic alumina using ethyl acetate–hexane (10:90) as the eluent. The bottom
phase was the ionic liquid containing the iodine and the produced water. The
2
341.
1
0. Typical procedure for the synthesis of IL 400: To a solution of PEG 400 (60 mmol)
and triethylamine (120 mmol) in toluene (200 mL) was added methylsulfonyl
chloride (10 mL) within 30 min under nitrogen atmosphere. The mixture was
stirred at room temperature. After 3 h, the mixture was filtrated. The filtrate
was added to 1-methylimidazol (120 mmol), and the mixture was stirred at
system of I
pressure.
2
/IL 400 was reused after removal of the water under reduced
8
6 °C for 17 h. After the reaction, the ionic liquid layer was separated and
washed with petroleum ether (3 Â 10 mL). Evaporation of solvent under