2-(Sulfooxy)propane-1,2,3-tricarboxylic acid as novel and versatile catalyst for the formylation of alcohols and amines using ethyl formate under neat conditions

Article abstract of DOI:10.1016/j.cclet.2012.01.041

2-(Sulfooxy)propane-1,2,3-tricarboxylic acid (supported on silica gel) has been introduced as novel and green catalyst for the formylation of alcohols and amines with ethyl formate, as mild formylation agent, under neat conditions at room temperature.. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Full text of DOI:10.1016/j.cclet.2012.01.041

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 450–453
www.elsevier.com/locate/cclet
2
-(Sulfooxy)propane-1,2,3-tricarboxylic acid as novel and versatile
catalyst for the formylation of alcohols and amines using ethyl
formate under neat conditions
*
Arash Ghorbani-Choghamarani , Ziba Akbaripanah
Department of Chemistry, Faculty of Science, Ilam University, P.O. Box 69315516, Ilam, Iran
Received 28 November 2011
Available online 3 March 2012
Abstract
2
-(Sulfooxy)propane-1,2,3-tricarboxylic acid (supported on silica gel) has been introduced as novel and green catalyst for the
formylation of alcohols and amines with ethyl formate, as mild formylation agent, under neat conditions at room temperature.
2012 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
#
Keywords: Alcohol; Amine; 2-(Sulfooxy)propane-1,2,3-tricarboxylic acid; Formylation; Ethyl formate
Finding molecules which are able to catalyze the reaction between others is an important contribution of molecular
chemists to increase the efficiency of chemical reactions whereby our daily life based on consumption of chemicals is
shifted closer to an ecologically and economically tolerable equilibrium with our environment [1]. The development
of heterogeneous catalysts for fine chemicals synthesis has become a major area of research mainly because the
reactions are carried out under mild conditions and the organic products are easily isolated from the reaction media.
Formylation of alcohols and amines is an important transformation in organic synthesis and provides an efficient
method for protection of hydroxyl and amino groups [2]. O-Formylation might be the method of choice for protecting
a hydroxyl group in a complex synthetic sequence because deformylation can be occurred selectively in the presence
of acetate or other ester groups. Also, formamides are Lewis bases, valuable intermediates in the synthesis of
pharmaceutically compounds [3,4], catalysts for organic transformations and reagents in Vilsmeier formylation.
Even though, various formylating systems have been presented in the literatures in the last years [5–10], there are
still serious limitations for the preparation of alkyl formats and formamides due to the drastic reaction conditions.
Therefore, in this project a new catalytic procedure has been designed for the formylation of alcohols and amines.
In continuation of our ongoing effort to find new catalysts or catalytic systems [11–16], we decided to prepare 2-
(
sulfooxy)propane-1,2,3-tricarboxylicacid (Fig. 1) as new catalyst for the preparation offormamides and alkyl formates.
-(Sulfooxy)propane-1,2,3-tricarboxylic acid was prepared via reaction of citric acid with chlorosulfonic acid
ClSO H) (Scheme 1). Because of gummy properties of this compound, it was supported on silica gel and applies as
2
(
3
catalyst for the formylation of alcohols and amines.
*
Corresponding author.
E-mail addresses: arashghch58@yahoo.com, a.ghorbani@mail.ilam.ac.ir (A. Ghorbani-Choghamarani).
1001-8417/$ – see front matter # 2012 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2012.01.041

A. Ghorbani-Choghamarani, Z. Akbaripanah / Chinese Chemical Letters 23 (2012) 450–453
451
O
OH
HO SO
HO
3
OH
O
O
Fig. 1. 2-(Sulfooxy)propane-1,2,3-tricarboxylic acid.
O
OH
O
OH
HO
HO
HO SO
3
ClSO H
3
OH
HO
OH + HCl
rt
O
O
O
O
Scheme 1. Preparation of 2-(sulfooxy)propane-1,2,3-tricarboxylic acid.
Table 1
Formylation of 2-phenylethanol by ethyl formate under different conditions.
a
b
Entry
Catalyst
Solvent
Time (h)
Yield (%)
1
2
3
4
5
6
2-(Sulfooxy)propane-1,2,3-tricarboxylic acid
2-(Sulfooxy)propane-1,2,3-tricarboxylic acid
2-(Sulfooxy)propane-1,2,3-tricarboxylic acid
No catalyst
Chloroform
Acetonitrile
n-Hexane
24
25
45
20
5
24
24
Solvent-free
Solvent-free
Solvent-free
24
Citric acid
24
25
94
2-(Sulfooxy)propane-1,2,3-tricarboxylic acid
2.25
a
Substrate/catalyst/ethyl formate for entries 1–3: 1 mmol/0.13 g/2 mmol; for entry 4: 1 mmol/–/2 mL; for entry 5: 1 mmol/0.2 mmol/2 mL; for
entry 6: 1 mmol/0.13 g/2 mL.
b
Isolated yield.
Initially, in order to find optimal conditions, 2-phenylethanol was formylated in different conditions. The results
have been presented in Table 1.
As is evident from Table 1, the reaction of 2-phenylethanol as a model compound with ethyl formate was examined
under various conditions. The reaction in the absence of catalyst and solvent produced only a trace amount of product.
The yields were somewhat increased in the presence of catalyst. The solvent screening has also been studied. The best
yields were obtained with 0.13 g of supported 2-(sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel and 2 mL of
ethyl formate under solvent-free conditions at room temperature. This optimal condition has been applied for all of the
formylation reactions.
Consequently, herein we disclosed a new catalytic protocol for the formylation of primary, secondary and tertiary
alcohols; also primary amines to produce the corresponding formylated products, using ethyl formate and a catalytic
amount of supported 2-(sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel under neat conditions, at room
temperature (Scheme 2 and Table 2).
O- and N-formylation of alcohols and amines was carried out heterogeneously under mild and solvent-free
conditions. Alkyl formate or formamide easily obtained by mixing 1 mmol of alcohol or amine, 0.13 g of supported 2-
(
sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel and 2 mL of ethyl formate; then stirring of the resulting
O
OH
O
HO SO
3
HO
OH
/Silica gel
X
X
O
R
H
R
CHO
CH CH OCHO, rt
3
2
R= Alkyl or aryl; X= O or N
Scheme 2. Formylation of alcohols and amines.

452
A. Ghorbani-Choghamarani, Z. Akbaripanah / Chinese Chemical Letters 23 (2012) 450–453
Table 2
Formylation of alcohols and amines using ethyl formate in the presence of catalytic amounts of supported 2-(sulfooxy)propane-1,2,3-tricarboxylic
a
acid on silica gel under neat conditions at room temperature.
b
Entry
Substrate
Product
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
CH
CH
CH
3
3
3
–(CH
–(CH
–(CH
2
2
2
)
)
)
2
3
6
–CH
–CH
–CH
OH
2
2
2
OH
OH
OH
CH
CH
CH
3
3
3
–(CH
–(CH
–(CH
2
2
2
)
)
)
2
3
6
2
–CH
–CH
–CH
2
2
2
OCHO
OCHO
OCHO
3
85
75
95
94
80
90
75
95
65
90
92
94
86
96
90
90
85
80
40
3
4
PhCH
PhCH
2
–CH
2
PhCH
PhCH
2
–CH
OCHO
OCHO
OCHO
OCHO
CH OCHO
CH OCHO
2.25
24
2
–C(CH
CH
CH
3
)
2
OH
OH
OH
CH
2
–C(CH
CH
CH
3 2
)
p-Cl–C
p-Br–C
p-tert-Bu–C
6
H
4
2
p-Cl–C
p-Br–C
p-tert-Bu–C
p-NO –C
PhNHCHO
p-Me–C
p-Et–C
2-MeO–C
p-F–C NHCHO
p-Cl–C NHCHO
p-Br–C NHCHO
Ph CH NHCHO
3-NO –C NHCHO
–N(CHO)–C
6
H
4
2
7.75
8
6
H
4
2
6
H
4
2
6
H
4
2
OH
6
H
4
2
16.5
12
p-NO
2
–C
6
H
4
CH
2
OH
2
6
H
4
2
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
PhNH
2
7.5
7.5
12.5
10
p-Me–C
6
H
4
NH
2
6
H
4
NHCHO
NHCHO
NHCHO
p-Et–C
2-MeO–C
p-F–C
p-Cl–C
p-Br–C
PhCH NH
3-NO –C
–NH–C
6
H
4
NH
2
6 4
H
6
H
4
NH
2
6
H
4
6
H
4
NH
2
6
H
4
12.5
9.5
13
6
H
4
NH
NH
2
6 4
H
6
H
4
2
6 4
H
2
2
2
1.5
25
2
6
H
4
NH
2
2
6 4
H
C
6
H
5
6
H
5
C
6
H
5
6
H
5
24
a
Substrate/catalyst/ethyl formate: 1 mmol/0.13 g/2 mL.
Isolated yield.
b
mixture at room temperature. After reaction completion, water was added in the mixture and pure product might be
easily obtained via extraction by dichloromethane (for alcohols) or ethyl acetate (for amines).
Results of Table 2 show that the unhindered alcohols reacted faster than the hindered ones. Also we could not get
good yields for the secondary amines (Table 2, entry 19).
Suggested mechanism has been outlined in Scheme 3.
Consequently, we have introduced a highly efficient solvent-free reaction for O-formylation and N-formylation
using a nontoxic and inexpensive catalyst. The advantages of this procedure are the avoidance of metallic
catalysts, mild and heterogeneous reaction conditions, avoidance of corrosive and toxic reagents and operational
simplicity.
O
C
EtO
H
O
OH
O
H
H
X
C
-
O SO
O
OH
O
3
HO
OH
EtO
HO SO
3
HO
OH
R
O
O
R
XH
XCHO+ EtOH
X= O or N
Scheme 3. Mechanism of O and N-formylation.

A. Ghorbani-Choghamarani, Z. Akbaripanah / Chinese Chemical Letters 23 (2012) 450–453
453
1
. Experimental
Chemicals were purchased from Fluka, Merck and Aldrich chemical companies. The formylated products were
1
13
characterized by comparison of their spectral (IR, H NMR, and C NMR) and physical data with authentic samples.
Preparation of supported 2-(sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel: A 500 mL suction flask
containing citric acid (48.0 g, 0.25 mmol) was equipped with a constant-pressure dropping funnel containing
chlorosulfonic acid (29.1 g, 0.25 mol) and gas inlet tube (the HCl created during the reaction was trapped in water).
Chlorosulfonic acid was added dropwise over a period of 30 min at room temperature. HCl gas evolved from the
reaction vessel immediately. Then the mixture was shaken for 60 min and kept in 50 8C for 4 h. Finally, silica gel
(
30 g) added to the obtained gummy product (i.e. 2-(sulfooxy)propane-1,2,3-tricarboxylic acid) and a white solid was
obtained quantitatively.
-(Sulfooxy)propane-1,2,3-tricarboxylic acid: Gummy solid, H NMR (300 MHz, CDCl ): d 10.62 (br, 4H), 1.63–
1
2
3
1
3
1
.51 (m, 4H); C NMR (75 MHz, CDCl ): d 175.2, 172.0, 71.9, 41.7.
3
General procedure for the formylation of alcohols and amines using ethyl formate in the presence of supported 2-
sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel: To a mixture of alcohol or amine (1 mmol) and ethyl formate
(
(
2 mL), supported 2-(sulfooxy)propane-1,2,3-tricarboxylic acid on silica gel (0.13 g) was added, then the reaction
mixture was stirred with a magnetic stirrer at room temperature for appropriate time. The progress of the reaction was
monitored by TLC. After reaction completion, water (10 mL) was added to the mixture; then formylated product
extracted with CH Cl (for alcohol) or EtOAc (for amine) (3Â 5 mL). The organic layer was then dried over anhydrous
2
2
Na SO (1.5 g). Finally, organic solvent was evaporated and pure product obtained in appropriate yield.
2
4
1
4
N-(4-Ethylphenyl) f ormamide: H NMR (300 MHz, CDCl ): d 8.67 (s, 1H), 8.34 (s, 1H), 7.48 (d, 2H, J = 8.2 Hz),
-Nitrobenzyl formate: H NMR (300 MHz, CDCl ): d 8.11 (s, 1H), 7.51–7.32 (m, 4H), 5.13 (s, 2H).
3
1
3
1
.04 (d, 2H, J = 8.2 Hz), 2.64 (q, 2H, J = 7.3 Hz), 1.22 (t, 3H, J = 7.3 Hz); C NMR (75 MHz, CDCl ): d 162.8, 129.1,
3
7
3
1
28.4, 120.2, 119.3, 28.3, 15.6.
N-(2-Methoxyphenyl) f ormamide: H NMR (300 MHz, CDCl ): d 8.45 (s, 1H), 7.85 (s, 1H), 7.23–6.90 (m, 4H),
.87 (s, 3H).
1
3
3
Acknowledgment
Financial support for this work by the Ilam University, Ilam, Iran is gratefully acknowledged.
References
[
[
[
[
[
[
[
[
[
1] A. Togni, A. Gr u¨ tzmacher, Catalytic Heterofunctionalization, Wiley-VCH Verlag GmbH, 2001.
2] R. Ghorbani-Vaghei, H. Veisi, M. Amiri, J. Iran. Chem. Soc. 6 (2009) 761.
3] K. Kobayashi, S. Nagato, M. Kawakita, et al. Chem. Lett. 575 (1995).
4] B.C. Chen, M.S. Bednarz, R. Zhao, et al. Tetrahedron Lett. 41 (2000) 5453.
5] D.R. Hill, C.N. Hsiao, R. Kurukulasuriya, et al. Org. Lett. 4 (2002) 111.
6] F. Shirini, K. Marjani, H.T. Nahzomi, et al. Phosphorus Sulfur Silicon Relat. Elem. 182 (2007) 1245.
7] K. Niknam, M.A. Zolfigol, D. Saberi, et al. Chin. J. Chem. 27 (2009) 1548.
8] V. Mirkhani, S. Tangestaninejad, S. Moghadam, et al. Monatsh. Chem. 135 (2004) 1257.
9] M.A. Zolfigol, G. Chehardoli, M. Dehghanian, et al. J. Chin. Chem. Soc. 55 (2008) 885.
[
[
[
[
[
[
[
10] A. Ghorbani-Choghamarani, M. Norouzi, Bull. Korean Chem. Soc. 32 (2011) 1399.
11] A. Ghorbani-Choghamarani, Z. Chenani, S. Mallakpour, Synth. Commun. 39 (2009) 4264.
12] A. Ghorbani-Choghamarani, M.A. Zolfigol, M. Hajjami, et al. Collect. Czech. Chem. Commun. 75 (2010) 607.
13] A. Ghorbani-Choghamarani, J. Zeinivand, J. Iran. Chem. Soc. 7 (2010) 190.
14] A. Ghorbani-Choghamarani, H. Goudarziafshar, M. Nikoorazm, et al. Lett. Org. Chem. 6 (2009) 335.
15] A. Ghorbani-Choghamarani, M.A. Zolfigol, R. Ayazi-Nasrabadi, J. Braz. Chem. Soc. 21 (2010) 33.
16] A. Ghorbani-Choghamarani, M.A. Zolfigol, M. Hajjami, et al. Lett. Org. Chem. 7 (2010) 249.