Mn(OAc)2/Schiff base as a new efficient catalyst system for the Henry reaction of nitroalkanes with aldehydes

Article abstract of DOI:10.1016/j.cclet.2012.04.018

A series of novel Schiff bases bearing triazole structure were synthesized and characterized by IR and NMR. Mn(OAc)₂/Schiff base efficiently catalyzed Henry reaction of nitroalkanes with aldehydes to produce the corresponding products of β-nitroalcohols, under mild conditions with high yields (up to 99%). A reaction mechanism is proposed based on the experimental results.

Full text of DOI:10.1016/j.cclet.2012.04.018

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 690–694
www.elsevier.com/locate/cclet
Mn(OAc)2/Schiff base as a new efficient catalyst system for the
Henry reaction of nitroalkanes with aldehydes
Guang Peng Zhou, Yong Hai Hui, Ning Ning Wan, Qiu Ju Liu,
*
*
Zheng Feng Xie , Ji De Wang
Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education and Xinjiang Uyghur Autonomous Region,
College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, China
Received 5 March 2012
Available online 14 May 2012
Abstract
A series of novel Schiff bases bearing triazole structure were synthesized and characterized by IR and NMR. Mn(OAc)2/Schiff
base efficiently catalyzed Henry reaction of nitroalkanes with aldehydes to produce the corresponding products of b-nitroalcohols,
under mild conditions with high yields (up to 99%). A reaction mechanism is proposed based on the experimental results.
# 2012 Zheng Feng Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Schiff base; Henry reaction; Aldehydes; Nitroalkanes
The Henry reaction, an aldol-type reaction, has been recognized as one of the most fundamental carbon–carbon
bond-forming reactions [1–3]. Products afforded by this reaction can be transformed into various valuable nitrogen-
containing building blocks, such as a-hydroxy ketones, aldehydes, carboxylic acids, azides, sulfides, and other
important bifunctional compounds [4,5], through either oxidation, reduction [6] or dehydration [7,8]. In particular, a
group of b-amino alcohol derivatives [9–11], which have been widely used as catalyst and important building blocks
of natural products [12] or pharmaceuticals [13], can be conveniently obtained by the reduction of b-hydroxy
nitroalkanes. Recent efforts have been focused on the development of catalytic systems due to the most important role
they play in above-mentioned reaction. According to previous reports, this type of C–C bond-forming reaction has
been demonstrated can be catalyzed by a range of inorganic, organic bases [14] and earth metal complexes [15–18]. In
the past few years, many chemists demonstrated that metal complexes such as copper [19–21], zinc [22,23],
chromium, indium, cobalt [24,25], cesium [26], ytterbium [27], and magnesium [28,29] catalyze Henry reaction.
However, several drawbacks, such as moisture or air sensitivity, necessity for bases, and difficult preparation of the
catalysts, still was lie ahead [30].
Our groups have successfully synthesized a series of triazole-containing Schiff base ligands L1–L6 (chemical
structure of these ligands are shown in Fig. 1) and demonstrated that such ligands can act as bi-functional
organocatalysts in Friedel–Crafts alkylation of indoles [31,32]. In continuation of our ongoing interest, we find that
* Corresponding authors.
E-mail addresses: xiezhf72@yahoo.com.cn (Z.F. Xie), awangjd@xju.edu.cn (J. De Wang).
1001-8417/$ – see front matter # 2012 Zheng Feng Xie. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.04.018

G.P. Zhou et al. / Chinese Chemical Letters 23 (2012) 690–694
691
R1
N
N
N
N
L1:R1=CH3
L2:R1=CF3
L3:R1=Ph
N
N
OH
O
N
L + M
solvent, r.t.
+
NO2
R2 CH2NO2
R2=H or CH3
SH
R1
R1
H
L4:R2=CH3
L5:R2=CF3
L6:R2=Ph
R2
R2
N
N
N
N
N
N
SH
Fig. 1. Ligands used in the Henry reaction of benzaldehyde derivatives with nitroalkanes.
Screening of Metal Sourses
99
88
100
70
69
55
42
35
34
40
17
10
Co(OAc)2 Cu(OAc)2 Pb(OAc)2 Zn(OAc)2 Mn(OAc)2 MnCl2
Metal Sourse
MnSO4 MnCO3
Fig. 2. Screening of metal sources (all the reactions were carried out with L1 (5 mol%), metal salt (5 mol%) and 2-nitrobenzaldehyde (0.2 mmol),
nitromethane (0.6 mmol) in EtOH at room temperature for 24 h. Isolated yield by column chromatography).
complexes of these bases and some metal salts can effectively activate the reaction between nitroalkanes with various
aldehydes, and the corresponding nitroalcohol-derivative target products have been successfully obtained.
1. Results and discussion
The Henry reaction of 2-nitrobenzaldehyde (0.2 mmol) with nitromethane (0.6 mmol) as model substrate was
investigated by using L1–L6 (5 mol%) as catalyst (Fig. 1) in EtOH. L2–L6 as catalyst showed the worst potential in
this reaction, no product was obtained. However, only 6% yield was obtained with application of L1 as catalyst.
Previous report demonstrated that weak Lewis acidic metal bearing moderately basic charged ligands would
facilitate the reaction of nitroalkanes with aldehydes. Inspired by this finding, we used several L/metal salts complexes
to catalyze the same reaction, and the corresponding results were summarized in Figs. 2 and 3. The best result was
achieved when using L1/Mn(OAc)2, and the very high yield (99%) implying its promising potential in such reaction in
the polar solvent, EtOH.
Table 1 listed the yield results of various nitroalkanols (3a–3t) afforded by condensation between different
aldehydes and nitroalkanes using L1–Mn(II) (5 mol%, 1:1) as a catalyst. In general, high yields (91–99%) were
observed when benzaldehyde derivatives bearing electron-withdrawing groups (Table 1, entries 2–8). In contrast,
Screening of Ligands
99
100
95
90
85
80
75
95
91
88
86
83
L1
L2
L3
L4
L5
L6
Ligand
Fig. 3. Screening of ligands (all the reactions were carried out with L (5 mol%), Mn(OAc)2 (5 mol%) and 2-nitrobenzaldehyde (0.2 mmol),
nitromethane (0.6 mmol) in EtOH at room temperature for 24 h. Isolated yield by column chromatography).

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G.P. Zhou et al. / Chinese Chemical Letters 23 (2012) 690–694
Table 1
Henry reaction of benzaldehyde derivatives with nitromethane using L1/Mn(OAc)2 in the presence of ethanol.a
Entry
1
R1
Ph
R2
H
Prod.
Yieldb (%)
71
Entry
12
R1
R2
H
Prod.
Yieldb (%)
57
3a
CH3CH2CH2
3l
2
4-NO2C6H4
H
3b
95
13
N
N
H
3m
88
N
3
4
3-NO2C6H4
2-NO2C6H4
H
H
3c
99
99
14
15
H
H
3n
3o
71
80
O
3d
N
5
4-ClC6H4
H
3e
91
16
H
3p
72
CH3
Cl
N
N
6
7
8
9
3-ClC6H4
H
H
H
H
3f
93
92
97
98
17
18
19
20
3-NO2C6H4
2-CH3OC6H4
2, 4-Cl2C6H4
Ph
CH3
CH3
CH3
CH3
3q
3r
3s
3t
85
12
35
10
3-BrC6H4
2,4-Cl2C6H4
2-OHC6H4
3g
3h
3i
10
4-CH3OC6H4
H
3j
78
21
H
3u
47
11
2-CH3OC6H4
H
3k
89
a
All the reactions were carried out using L1 (5 mol%), Mn(OAc)2 (5 mol%) as catalyst in ethanol at room temperature. benzaldehyde derivatives
and other aldehydes (0.2 mmol), nitromethane (0.6 mmol).
b
Isolated yield by column chromatography.
aromatic aldehydes containing electron-donating groups gave the corresponding product in relatively low yield (Table
1, entry 10). And in the reaction of aromatic aldehydes containing both electron-withdrawing and electron-donating
groups in the aromatic ring’s ortho-position, the reaction proceeded smoothly in high yields (Table 1, entries 4, 9, and
11). Aliphatic branched, heteroaromatic and cinnamic aldehydes were also acceptable substrates, affording nitro
alcohol adducts in good yields (Table 1, entries 12–16, 21). Surprisingly, benzaldehyde derivative containing hydroxyl
group was converted to nitroaldol product 3h in almost quantitative yield (Table 1, entry 9). When nitroethane was
used, relatively low yields of corresponding nitroalcohols were obtained under the same condition in EtOH, implying
the significant influence brought by the electronic nature of nitroethane, regardless of the substituent on the ring is
L
L
+ M
0
10
20
30
2 Theta
40
50
60
Fig. 4. Powder X-ray diffraction patterns of (L) Schiff base (L + M) corresponding manganese complex.

G.P. Zhou et al. / Chinese Chemical Letters 23 (2012) 690–694
693
L
L
+ M
0
500
1000
1500
2000
2500
3000
- 1
3500
4000
4500
wavenumber cm
Fig. 5. FT-IR spectra of (L) Schiff base (L + M) corresponding manganese complex.
Fig. 6. Plausible transition structures for the Henry reaction.
electron-withdrawing or electron-donating (Table 1, entries 17–20). The reason might be explained by the lower pKa
value of nitroethane than nitromethane (8.456 and 10.211 at 25 8C, respectively) [9].
Powder X-ray diffraction (XRD) patterns were collected with XRD, D8, Advance, Bruker, AXS, using a nickel-
filtered Cu Ka (0.154056 nm) radiation source at 40 kVand 50 mA in the range of 2u = 5–608. XRD spectra (Fig. 4) of
the L before and after manganese loading showed a change. IR spectrum of the complex showed that 1619 cmÀ1 for
n(C N) and 2552 cmÀ1 for n(S–H) were disappeared in Fig. 5. In addition, IR spectrum of the complex showed an
absorption bands at 501 cmÀ1, which was attributed to the formation of Mn–N. These variations could be confirmed
the coordination of manganese ion with the Schiff base ligand.
Although attempts to detail the reaction mechanism have not been undertaken, a possible cycle can be proposed
(Fig. 6). From the mechanistic point of view, the initial step involves deprotonation of nitromethane by catalyst to give
the intermediate A. Consequent stripping of HOAc moiety to give the intermediate B that can make nitromethane more
nucleophilic and liable to attack on aldehydes to give the intermediate C. Then with the HOAc moiety, the
corresponding products D will be afforded and the catalyst is recovered to its initial state.
In summary, our results showed that the complex of Mn(II)–Schiff base L1 was an effective catalyst for the Henry
reaction and produced b-hydroxy nitroalkanes in high yield. The procedure with above-mentioned catalyst has several
merits including simplicity of operation, mild reaction condition and easy isolation. What’s more, the insight into the
mechanism will provide useful information to synthesize b-nitroalcohols. Further work is in under progress with the
aim of expanding the applications of these inexpensive ligands to other catalytic processes.
Acknowledgment
We appreciate the financial support from the National Natural Science Foundation of China (Nos. 20962018,
20862015 and 20562011).

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G.P. Zhou et al. / Chinese Chemical Letters 23 (2012) 690–694
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