Imidazole-catalyzed henry reactions in aqueous medium

Article abstract of DOI:10.1080/00397910802045592

2-Nitroalkanols can be efficiently synthesized using imidazole as a mild Lewis basic catalyst in aqueous medium as well as in organic solvents. The products have been found in good yields without purification (>95% purity by 1H NMR) for aromatic aldehydes

Full text of DOI:10.1080/00397910802045592

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Imidazole-Catalyzed Henry
Reactions in Aqueous Medium
Mridula Phukan a , Kalyan Jyoti Borah a & Ruli Borah
a
a Chemical Sciences Department, Tezpur University,
Napaam, Tezpur, Assam, India
Version of record first published: 09 Sep 2008.
To cite this article: Mridula Phukan, Kalyan Jyoti Borah & Ruli Borah (2008):
Imidazole-Catalyzed Henry Reactions in Aqueous Medium, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
38:18, 3068-3073
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Synthetic Communications1, 38: 3068–3073, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802045592
Imidazole-Catalyzed Henry Reactions in
Aqueous Medium
Mridula Phukan, Kalyan Jyoti Borah, and Ruli Borah
Chemical Sciences Department, Tezpur University, Napaam,
Tezpur, Assam, India
Abstract: 2-Nitroalkanols can be efficiently synthesized using imidazole as a
mild Lewis basic catalyst in aqueous medium as well as in organic solvents.
The products have been found in good yields without purification (>95% purity
by 1H NMR) for aromatic aldehydes. Additionally, the very mild reaction
conditions prevent the particular side reactions such as aldol condensation,
Cannizzaro reaction, or dehydration of the 2-nitro alcohols into nitro alkenes
even if aromatic aldehydes are used. This report satisfies the criteria for green
synthesis in terms of reaction medium and recycling of the catalyst (imidazole).
Keywords: Aqueous medium, Henry reaction, imidazole, nitroalkane
INTRODUCTION
b-Nitroalkanols are considered useful intermediates in organic synthesis
for various transformations,[1–3] especially for the synthesis of nitroalk-
enes, 2-amino alcohols, and 2-nitro-ketones. Moreover, they are also
important as fungicides.[4] The nitroaldol reaction (Henry reaction)
involves base-catalyzed addition of nitroalkanes to a carbonyl com-
pound.[5,6] Several catalysts such as alkali metal hydroxides, alkaline
earth oxides, carbonates, bicarbonates, alkoxides, and quaternary
ammonium salts have been used for the nitroaldol reactions. However,
nitroaldol reactions are associated with various competitive reactions[7,8]
such as aldol condensation, Cannizzaro reaction, Tishchenko reaction,
Received October 24, 2007.
Address correspondence to Ruli Borah, Senior Lecturer, Department of
Chemical Sciences, Tezpur University, Napaam, Tezpur 784028, Assam, India.
E-mail: ruli@tezu.ernet.in
3068

Imidazole-Catalyzed Henry Reactions
3069
Scheme 1. Imidazole-catalyzed Henry reaction.
and Nef-type reaction. In addition, base-catalyzed elimination of water
can lead to nitro-olefin, which polymerizes readily.[9] Recently, many
new catalysts[10,11] have been developed for the Henry reaction such as
rhodium complex, KG-60-NEt2, 2:1 Mg–Al hydrotalcite, phosphine,
guanidines, proazaphosphatranes, and ionic liquids. The need to reduce
the amount of toxic waste and by-products arising from chemical
processes requires increasing attention to the use of less toxic and envir-
onmentally compatible materials in the design of new green methodolo-
gies.[12] Therefore, the development of new methodologies for the
preparation of 2-nitroalkanols is very attractive in terms of greener reac-
tion condition. Ballini and Bosica[13] reported an environmentally benign
synthesis protocol for nitroaldol reaction in aqueous medium using cetyl-
trimethyl–ammonium chloride as catalyst. In addition, Ballini et al.[14]
published another aqueous-phase Henry reaction in the presence of eco-
friendly catalyst cetyltrimethylammonium hydroxide (CTAOH) at room
temperature. In this communication, a new green synthetic method of
nitroaldol reaction (Scheme 1) is reported using imidazole as catalyst in
aqueous medium.
RESULTS AND DISCUSSION
In connection with our research interest in the development of green
syntheses,[15] initially we decided to evaluate the effect of solvent on the
imidazole-catalyzed Henry reaction in different organic solvents as well
as in an aqueous medium. For this study, the reaction between
p-nitrobenzaldehyde and nitromethane was chosen as a model. The reac-
tion proceeds smoothly at room temperature in water (Table 1, entry 4)
with 98% yield of b-nitroalcohol in 30 min. The reaction was carried out
at room temperature in organic solvents such as dichloromethane, 1,4-
dioxane, chloroform, tetrahydrofuran, acetonitrile, and methanol
(Table 1). In the case of solvents such as dichloromethane, 1,4-dioxane,
and chloroform (Table 1, entries 1–3) the conversions were quite similar
to aqueous medium. Interestingly, the use of polar aprotic and protic
organic solvents such as tetrahydrofuran, acetonitrile, and methanol

3070
M. Phukan, K. J. Borah, and R. Borah
Table 1. Effect of solvent on the imidazole-catalyzed reactions of p-nitrobenzal-
dehyde with nitromethane
Time Nitroalcohola,b
Entry
Solvent
Nitroalkane (min)
yield (%)
1
2
3
4
5
6
7
8
9
Dichloromethane
1,4-Dioxane
Chloroform
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
35
25
30
30
5
5
5
5
5
94
93
92
98
95
95
94
92
95
91
92
90
Water
Tetrahydrofuran
Acetonitrile
Methanol
Tetrahydrofuran–water (1:1)
Acetonitrile–water (1:1)
Methanol–water (1:1)
Dichloromethane–water (1:1)
Chloroform–water (1:1)
10
11
12
5
35
35
aReactions were carried out on a 0.5-mmol scale (2 ml of solvent) in the molar
ratio of aldehyde=nitromethane=catalyst ¼ 1:3:0.25.
bIsolated yields of pure products.
(Table 1, entries 5–7) gave excellent conversion to the nitroaldol product
within 5 min. This can be explained in terms of a homogeneous solution
of reaction mixture with the catalyst imidazole in polar organic solvent,
which possesses a slight amount of miscible water. Again, the reactants
are in a different phase with the catalyst imidazole in a less polar organic
solvent. Similarly, for an aqueous medium, the reactants are in different
phases with the water-soluble catalyst imidazole. Thus, the aqueous
medium reaction took a similar reaction period to less polar organic sol-
vents. Carrying out the same reaction in a 1:1 mixture of various organic
solvents and water medium (Table 1, entries 8–12) can indirectly prove
this explanation. It was observed that the reaction completed within
35 min in a heterogeneous 1:1 mixture of less polar organic and aqueous
solvent systems (Table 1, entries 11 and 12). Similarly, a homogeneous
1:1 mixture of polar organic and aqueous solvent systems showed compa-
rable results with the polar organic solvent (Table 1, entries 8–10).
We next examined the extent and feasibility of the imidazole-
catalyzed aqueous Henry reaction of nitroalkane with various aldehydes
(Table 2). For aryl aldehydes bearing electron-withdrawing groups, the
reaction took place smoothly to afford the desired nitroaldol products
in good to excellent yields (Table 2, entries 3–7). However, for arylalde-
hydes bearing electron-donating groups such as p-tolualdehyde, anisalde-
hyde (Table 2, entries 8–12), and aliphatic aldehyde (Table 2, entries 13

Imidazole-Catalyzed Henry Reactions
3071
Table 2. Henry reaction in aqueous medium
a,bProduct (3)
yield (%)
Entry
R0 (1)
Nitroalkane (2)
Time
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
C6H5
C6H5
CH3NO2
CH3CH2NO2
CH3NO2
CH3NO2
CH3NO2
CH3CH2NO2
CH3CH2NO2
CH3NO2
CH3CH2NO2
CH3NO2
CH3NO2
15 min
30 min
30 min
15 min
15 min
15 min
15 min
45 min
2 h
90 min
3 h
1 h
12 h
12 h
90
88
98
97
90
85
94
96
87
97
95
96
60
55
65
4-O2N-C6H4
2-O2N-C6H4
3-O2N-C6H4
4-O2N-C6H4
3-O2N-C6H4
4-MeC6H4
4-OMeC6H4
2-OHC6H4
4-ClC6H4
4-MeC6H4
Pentanal
CH3CH2NO2
CH3CH2NO2
CH3NO2
Pentanal
Furyl
CH3CH2NO2
4 h
aAll products were characterized by FT-IR, 1H NMR, CHN analyzer and also
their comparison with authentic sample.
bIsolated yields.
and 14), the reactions were slow. Similarly, the reaction of furaldehyde
(Table 2, entry 15) with nitroethane was slow, resulting in 65% of the
corresponding nitroalcohol after 4 h. The role of the imidazole catalyst
appears to be that of a base that deprotonates the nitromethane, facilitating
Scheme 2. Possible reaction mechanism.

3072
M. Phukan, K. J. Borah, and R. Borah
the nitroaldol reaction (Scheme 2). In addition, the imidazole-
containing aqueous phase (after extraction of the product) was recycled
(Table 2, entry 4) three times using a similar amount of 2-nitrobenzalde-
hyde (1 mmol).
EXPERIMENTAL
General Method for Henry Reaction in Aqueous Medium
A mixture of 2-nitrobenzaldehyde (1 mmol), nitromethane (3 mmol), and
imidazole (0.25 mmol) was charged with 2 ml of distilled water. The
heterogeneous reaction mixture was stirred at ambient temperature
and monitored by thin-layer chromatography (TLC). After completion
of the reaction, the product was extracted with 10 ml of diethyl ether.
The organic layer was dried over anhydrous sodium sulfate and filtered.
The organic filtrate was evaporated under reduced pressure and dried
under vacuum to give the crude product, which is reasonably pure
(>95% purity by 1H NMR) for aromatic aldehydes. However, the residue
was further purified by preparative TLC on silica gel to give the desired
analytically pure products.
CONCLUSION
In summary, we have developed a new environmentally benign Henry
reaction condition in aqueous media using imidazole as catalyst. The
catalyst can be reused several times without appreciable loss of activity.
ACKNOWLEDGMENT
The authors are thankful to the Council of Scientific and Industrial
Research, New Delhi, India, for granting a research grant (No.
01(2067)=06=EMR-II) to R. B.
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Imidazole-Catalyzed Henry Reactions
3073
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