1-Butyl-3-methyl-imidazolium tetrafluoroborate as a recyclable reaction medium for henry reaction

Article abstract of DOI:10.1081/SCC-200048415

A simple protocol for the Henry reaction has been developed in room temperature ionic liquid [bmim]BF₄ using Na₂CO₃ as base. The 2-nitroalcohols have been obtained in good yields, and the ionic liquid was recycled.

Full text of DOI:10.1081/SCC-200048415

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1‐Butyl‐3‐methyl‐imidazolium
Tetrafluoroborate as a
Recyclable Reaction Medium
for Henry Reaction
Faiz Ahmed Khan a , Ch. Sudheer a & Nilam Sahu a
a Department of Chemistry , Indian Institute of
Technology , Kanpur, 208 016, India
Published online: 28 Jul 2007.
To cite this article: Faiz Ahmed Khan , Ch. Sudheer & Nilam Sahu (2005)
1‐Butyl‐3‐methyl‐imidazolium Tetrafluoroborate as a Recyclable Reaction Medium
for Henry Reaction, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:2, 201-207, DOI: 10.1081/
SCC-200048415
To link to this article: http://dx.doi.org/10.1081/SCC-200048415
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Synthetic Communicationsw, 35: 201–207, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048415
1-Butyl-3-methyl-imidazolium
Tetrafluoroborate as a Recyclable
Reaction Medium for Henry Reaction
Faiz Ahmed Khan, Ch. Sudheer, and Nilam Sahu
Department of Chemistry, Indian Institute of Technology, Kanpur, India
Abstract: A simple protocol for the Henry reaction has been developed in room temp-
erature ionic liquid [bmim]BF4 using Na2CO3 as base. The 2-nitroalcohols have been
obtained in good yields, and the ionic liquid was recycled.
Keywords: [bmim]BF4, Henry reaction, ionic liquid, Na2CO3, 2-nitroalcohols
INTRODUCTION
Room temperature ionic liquids (ILs) have been the subject of considerable
interest as new, nonvolatile, and environmental friendly alternatives to con-
ventional organic solvents. They are salts of organic cations and a variety
of anions. For reviews, see.[1–4] Ionic liquids are compatible with several
organic transformations;[5–7] they readily immobilize several catalysts in
their native form[8,9] or the supported catalysts.[10] They have been found to
alter the outcome of chemical reactions in a dramatic fashion,[11] thus
forming a new paradigm in organic synthesis.
The Henry (nitroaldol) reaction is one of the most prevailing C22C bond
forming reactions in organic chemistry to furnish 2-nitroalcohols[12]
(Scheme 1). The nitroalcohols are versatile building blocks for the synthesis
of nitroalkenes, 2-aminoalcohols, and nitro ketones.[12] Recently, we have
reported Henry reaction in ILs over solid base hydrotalcite catalyst.[13,14]
Received in India November 3, 2004
Address correspondence to Faiz Ahmed Khan, Department of Chemistry, Indian
Institute of Technology, Kanpur 208 016, India. E-mail: faiz@iitk.ac.in

202
F. A. Khan, Ch. Sudheer, and N. Sahu
Scheme 1. Nitroaldol reaction in ionic liquid [bmim]BF4.
Figure 1. 1-Butyl-3-methyl-imidazolium tetrafluoroborate.
Jiang and Han have reported Henry reactions catalyzed by guanidine-based
ILs,[15] wherein a large excess of the nitro alkane was used, thus limiting
the generalization of the procedure. Zhang and coworkers have reported
facile preparation of 2-nitroalcohols using [bmim]BF4 and DBU.[16] In con-
tinuation of our recent interest to use ILs as a green reaction media,[13,14]
we report herein Henry reaction, in reusable ionic liquid, [bmim]BF4
(Fig. 1) using Na2CO3 as base.
RESULTS AND DISCUSSION
We studied the title reaction in ionic liquid, 1-butyl-3-methylimidazolium
tetrafluoroborate1: [bmim]BF4, using Na2CO3 as base. Our results are summar-
ized in Table 1. Use of 2 equiv. of nitroalkane, 1 equiv. of Na2CO3 in 1 mL of
[bmim]BF4 for 0.5 mmol of 4-nitrobenzaldehyde gave a clean reaction with
the formation of 70% of the corresponding nitroalcohol (entry 2, Table 1).
On the basis of optimized result, the aromatic aldehydes were subjected
under similar conditions to furnish the corresponding nitroalcohols in
moderate to satisfactory yields (Table 1). Aliphatic aldehydes (entries 8 and
9, Table 1) also gave good yields of corresponding 2-nitroalcohols. The
reaction of 3,4,5-trimethoxy benzaldehyde with nitromethane was slow
resulting in 31% of the corresponding nitroalcohol (88% based on the
recovered starting material) after 24 hr. The reactions of benzaldehyde
(entry 1) and 4-phenyl benzaldehyde (entry 4) showed similar trends.
The separation of products from ionic liquid is very simple. After con-
sumption of the starting material, as monitored by TLC, diethyl ether or
11-Butyl-3-methylimidazolium tetrafluoroborate, [bmim]BF4, was prepared
following the procedure in.[17]

[bmim]BF4 as a Recyclable Medium for Henry Reaction
203
a
Table 1. Nitroaldol reaction of aromatic aldehydes using Na2CO3 in [bmim]BF4
Entry
1
Substrate
Time (hr)
24
Yield (%)b,c
53
2
3
3
4
70
65 (89)
4
5
45
4
43 (84)
72
6
7
12
24
59
31 (88)
8
9
CH3-(CH2)2-CHO
(CH3)2CH-CHO
6
93
81
10
aAll reactions were run by using 0.5 mmol of aldehyde, 1 mmol of nitromethane,
0.5 mmol of Na2CO3 in 1 mL of ionic liquid.
bIsolated yields of analytically pure products.
cYields in parentheses are based on the recovered starting aldehyde.
toluene (2 mL) was added to the reaction mixture and stirred for 5 min. The
mixture was allowed to stand for 5 min, and the clear supernatant liquid
was decanted. The separated diethyl ether or toluene layer was collected,
and the procedure was repeated until no product was detected (by TLC) in
diethyl ether or toluene extract.
The condensation of nitroethane proceeded efficiently in ionic liquid
medium with excellent yields (Scheme 2). However, the diastereoselectivities
of the reaction were not appreciable. Benzaldehyde gave a 35 : 65 mixture of

204
F. A. Khan, Ch. Sudheer, and N. Sahu
Scheme 2. Nitroaldol reaction using nitroethane.
syn : anti nitroalcohols and nitrobenzaldehyde furnished a 44 : 56 of syn : anti
1
nitroalcohols. The diastereomeric ratios were determined by H NMR inte-
gration at 400 MHz of the unpurified product mixtures obtained after extrac-
tion. The carbinol hydogen exhibits a vicinal coupling constant of 3.5–3.8 Hz
for syn nitroalcohols, and 8.6–9.0 Hz for anti nitroalcohols.
The facile recycling of the ionic liquid was shown for the Henry reaction
of 4-nitrobenzaldehyde. The residue containing ionic liquid (after extraction
of the product) was dissolved in EtOAc, filtered through a filter paper, dried
over Na2SO4, and the solvent was removed on a rotary evaporator. The
ionic liquid was further vacuum dried at 0.1 mm Hg for 1 hr and used for
two more runs under identical conditions as for run 1. The results are given
in Table 2. The recycling was further simplified wherein after the extraction
of the product as described above, the ionic liquid containing Na2CO3 was
vacuum dried to remove residual solvent of extraction (vacuum drying is
not essential for the success of the reaction) and used for the next reaction.
No cross contamination of the products was observed for nitroaldol reaction
of different substrates in the recycled ionic liquid (Table 3).
In summary, we have demonstrated that 2-nitroalcohols can be prepared in
good yields by the Henry reaction of aldehydes using the ionic liquid
[bmim]BF4 and Na2CO3. The ionic liquid containing Na2CO3 was reused for
Henry reaction of different aldehydes with no cross-contamination of products.
Table 2. Ionic liquid recycling for Henry reaction
of 4-nitrobenzaldehyde
Cycle
Time (hr)
Yield (%)a
1
2
3
5
6
6
70
72
68
aIsolated yields of analytically pure compounds.

[bmim]BF4 as a Recyclable Medium for Henry Reaction
205
Table 3. Recycling the reaction system: crossed experiments
Entry
RCHO
Cycle
Time (hr)
Yield (%)
1
2
3
4
n-BuCHO
n-BuCHO
1
2
3
4
6
5
93
91
70
52
4-NO2C6H4CHO
C6H5CHO
4
20
EXPERIMENTAL
General
1H NMR spectra were recorded as CDCl3 solutions using a JEOL NMR
spectrometer operating at 400 MHz; peak positions are reported as d (ppm)
downfield from internal Me4Si; peak multiplicities are reported as singlet
(s), doublet (d), triplet (t), quartet (q), or multiplet (m); broad signals are desig-
nated (br.). 13C NMR spectra were recorded as CDCl3 solutions at 100 MHz;
peak positions are reported as d (ppm).
Typical Experimental Procedure for Henry Reaction in [bmim]BF4
To a stirred solution of aldehyde (0.5 mmol) in 1 mL of [bmim]BF4 was added
anhydrous Na2CO3 (0.5 mmol) and nitroalkane (1 mmol) at room temperature
under an atmosphere of argon for the specified time (Table 1). After consump-
tion of the starting material, as monitored by TLC, diethyl ether or toluene
(2 mL) was added to the reaction mixture and stirred for 5 min. The mixture
was allowed to stand for 5 min and the clear supernatant liquid was
decanted. The separated diethyl ether or toluene layer was collected, and
the procedure was repeated until no product was detected in diethyl ether or
toluene layer. Concentration followed by silica gel column chromatography
gave the nitroalcohols in the specified yields.
The ionic solvent-Na2CO3 residue was dried at 408C/1 mmHg for 1 hr
and stored under inert atmosphere before reusing in next reaction.
The products were characterized by comparing the NMR with those
reported in literature.[18–21] NMR data of the 2-nitroalcohols that are not
reported earlier are given below.

206
F. A. Khan, Ch. Sudheer, and N. Sahu
1H NMR d7.58 (1 H, s), 7.51–7.48 (1 H, m), 7.34–7.26 (2 H, m), 5.44 (1 H, dd
J ¼ 9.3, 3.2 Hz), 4.58 (1 H, dd J ¼ 13.4, 9.3 Hz), 4.51 (1 H, dd J ¼ 13.4,
3.3 Hz), 3.04 (1 H, s) ppm. 13C NMR d140.3, 132, 130.5, 129.1, 124.5,
123.1, 80.9, 70.2 ppm.
1H NMR d7.1–7.01 (2 H, m), 6.91 (1 H, dd J ¼ 7.8, 1.7 Hz), 5.68–5.48 (1 H,
m), 4.63(1 H, dd J ¼ 13, 2.9 Hz), 4.51 (1 H, dd J ¼ 13, 9.5 Hz), 4.28–4.17
(1 H, m), 4.07–3.99 (1 H, m), 3.85 (3 H, s), 3.28(1 H, d J ¼ 5.1 Hz), 1.4
(3 H, t J ¼ 6.9 Hz) ppm.
1H NMR d6.6 (2 H, s), 5.39 (1 H, d J ¼ 9.5 Hz), 4.66–4.48 (2 H, m), 3.86 (6 H,
s), 3.82 (3 H, s) ppm.
ACKNOWLEDGMENTS
Financial support from the Department of Science and Technology (DST),
New Delhi is gratefully acknowledged. FAK acknowledges the DST for a
Swarnajayanti Fellowship. NS and ChS thank CSIR, UGC for fellowships.
REFERENCES
1. Dupont, J.; de-Souza, R. F.; Suarez, P. A. Z. Ionic liquid (molten salt) phase orga-
nometallic catalysis. Chem. Rev. 2002, 102, 3667.
2. Sheldon, R. A. Catalytic reactions in ionic liquids. Chem. Commun. 2001, 2399.
3. Wasserscheid, P.; Keim, W. Ionic liquids—new “solutions” for transition metal
catalysis. Angew. Chem. Int. Ed. 2000, 39, 3772.
4. Welton, T. Room-temperature ionic liquids. Solvents for synthesis and catalysis.
Chem. Rev. 1999, 99, 2071.
5. Brausch, N.; Metlen, A.; Wasserscheid, P. New, highly acidic ionic liquid systems
and their application in the carbonylation of toluene. Chem. Commun. 2004, 1552.
6. Li, D.; Shi, F.; Peng, J.; Guo, S.; Deng, Y. Application of functional ionic liquids
possessing two adjacent acid sites for acetalization of aldehydes. J. Org. Chem.
2004, 69, 3582.
7. Zhao, G.; Jiang, T.; Gao, H.; Han, B.; Haung, J.; Sun, D. Mannich reaction using
acidic ionic liquids as catalysts and solvents. Green Chem. 2004, 75.

[bmim]BF4 as a Recyclable Medium for Henry Reaction
207
8. Branco, L. C.; Afonso, C. A. M. Ionic liquids as a convenient new medium for the
catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable
osmium/ligand. J. Org. Chem. 2004, 69, 4381.
9. Geldbach, T. J.; Dyson, P. J. A. Versatile ruthenium precursor for biphasic
catalysis and its application in ionic liquid biphasic transfer hydrogenation: con-
ventional vs task-specific catalysts. J. Am. Chem. Soc. 2004, 126, 8114.
10. Hagiwara, H.; Sugawara, Y.; Isobe, K.; Hoshi, T.; Suzuki, T. Immobilization of
Pd(OAc)2 in ionic liquid on silica: application to sustainable mizoroki-heck
reaction. Org. Lett. 2004, 6, 2325.
11. Earle, M. J.; Katdare, S. P.; Seddon, K. R. Paradigm confirmed: the first use of
ionic liquids to dramatically influence the outcome of chemical reactions. Org.
Lett. 2004, 6, 707.
12. Luzzio, F. A. The Henry reaction: recent examples. Tetrahedron 2001, 57, 915.
13. Khan, F. A.; Dash, J.; Sudheer, Ch.; Gupta, R. K. Chemoselective reduction of
aromatic nitro and azo compounds in ionic liquids using zinc and ammonium
salts. Tetrahedron Lett. 2003, 44, 7783.
14. Khan, F. A.; Dash, J.; Satapathy, R.; Upadhyay, S. K. Hydrotalcite catalysis in
ionic liquid medium: a recyclable reaction system for heterogeneous Knoevenagel
and nitroaldol condensation. Tetrahedron Lett. 2004, 45, 3055.
15. Jiang, T.; Gao, H.; Han, B.; Zhao, G.; Chang, Y.; Wu, W.; Gao, L.; Yang, G. Ionic
liquid catalyzed Henry reactions. Tetrahedron Lett. 2004, 45, 2699.
16. Qian, W.; Ju, F.; Bao, W.; Zhang, Y. An efficient method for the preperation of
b-nitroalkanols in room temperature ionic liquids. J. Chem. Res. (S) 2004, 154.
17. Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; de-Souza, R. F.; Dupont, J. The use of
new ionic liquids in two-phase catalytic hydrogenation reaction by rhodium
complexes. Polyhedron 1996, 15, 1217.
18. Bulbule, V. J.; Deshpande, V. H.; Velu, S.; Sudalai, A.; Sivasankar, S.; Sathe, V. T.
Heterogeneous Henry reaction of aldehydes: diastereoselective synthesis of
nitroalcohol derivatives over Mg-Al hydrotalcites. Tetrahedron 1999, 55,
9325and references cited therein.
19. Choudary, B. M.; Kantam, M. L.; Kavita, B. Synthesis of 2-nitroalkanols by Mg-
Al-O-t-Bu hydrotalcite. J. J. Mol. Catal. A Chem. 2001, 169, 193.
20. Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.; Downey, C. W. A
new copper acetate-bis(oxazoline)-catalyzed, enantioselective Henry reaction.
J. Am. Chem. Soc. 2003, 125, 12692.
21. Kisanga, P. B.; Verkade, J. G. P(RNCH2CH2)3N: an efficient promoter for the
nitroaldol (Henry) reaction. J. Org. Chem. 1999, 64, 4298and references cited
therein.