4
Tetrahedron
and 6). Nitroalkenes 5 were obtained in good yields for all
of different types of amine-functionalized solid acids is
unnecessary for each reaction. Various kinds of amines and solid
acids can be employed easily depending on an individual
purpose. The procedure will be applied for various base-
catalyzed organic transformations as well as nitroaldol reactions
and furthermore, it is especially useful in laboratories.
examined cases in toluene (entries 2, 8, 10, 12, 14, 16, 18, 20,
and 21). Without silica gel, compound 5 was not obtained at all
(entry 3). When SBA-15 was used in toluene, the reactions
proceeded faster than those of silica gel to give 5 in good yields
in every case (entries 2, 4, 8, 9, 12, 13, 18, 19, 21, and 22).
As shown in Table 6, the use of Me2N(CH2)2NH2 in the
presence of silica gel at 50°C for 1 h in CH3NO2 led to the main
formation of 1,3-dinitroalkane 6a (entry 1). In this case, the NH2
group of Me2N(CH2)2NH2 would catalyze the formation of
compound 5a from 3a via 4a. The Me2N group would promote
the formation of compound 4a from 3a and compound 6a from
5a.31,32 Because Me2N(CH2)2NH2 possesses both NH2 and Me2N
groups in a molecule, compound 6a could become the major
product. In the absence of silica gel, the reaction was
considerably slow (entry 2). When Et3N and n-C6H13NH2 were
employed instead of Me2N(CH2)2NH2, lower yield (55%) of 6a
compared to that of Me2N(CH2)2NH2 (73%) was obtained
accompanied by 21 and 15% yields of compounds 4a and 5a,
respectively (entry 3). The addition of SBA-15 and MCM-41
resulted in the lower yields of 6a than that of silica gel (entries 1,
4, and 5).
Table 7
Me2N(CH2)2NH2-catalyzed reactions of aromatic aldehydes 3
a
enhanced by SiO2
Entry
Ar
Time (h)
Yield (%)b
1
2c
3
4
5
6
7
8
9
Ph (3a)
4
75
22d
32e
11f
77
75
72
70
70
24
24
24
4
4-ClC6H5 (3b)
4-O2NC6H5 (3f)
4-MeC6H5 (3g)
2-Naphthyl (3h)
4-MeOC6H5 (3i)
2-MeOC6H5 (3l)
2-Thienyl (3k)
4
8
8
8
Table 6
Me2N(CH2)2NH2-catalyzed reactions of 3a in the presence of
solid supportsa
a
Aldehyde 3 (2.0 mmol), Me2N(CH2)2NH2 (0.2 mmol), SiO2 (200 mg),
CH3NO2 (2 mL), 50 °C.
b Isolated yields.
Yield (%)b
c
Aldehyde 3 (2.0 mmol), Me2N(CH2)2NH2 (0.2 mmol), SiO2 (200 mg),
Entry
Additive
CH3NO2 (4.4 mmol), toluene (4 mL), 90 °C.
d Compound 5a was obtained in 47% yield
e Compound 4b was obtained in 26% yield
f Compound 4f was obtained in 56% yield
4a
5a
6a
1
SiO2
0
23
32
15
55
53
73
18
55
43
46
2c
3d
4
-
18
21
0
SiO2
Acknowledgments
SBA-15
MCM-41
We thank Center for Instrumental Analysis, Institute for
Research Promotion, Niigata University for NMR measurements.
We thank the Research Promotion Grant (NDU Grants N-17009)
from Nippon Dental University.
5
0
a
Aldehyde 3a (2.0 mmol), Me2N(CH2)2NH2 (0.2 mmol), additive (200 mg),
CH3NO2 (2 mL), 50 °C, 1h.
b Yields were determined by 1H NMR with acetone as the internal standard..
c 3a was recovered in 30%.
Et3N (0.2 mmol) and n-C6H13NH2 (0.2 mmol) were used instead of
Me2N(CH2)2NH2.
d
Supplementary data
Supplementary data (general experimental procedures, data of
IR and NMR spectra of the products, and recycle experiments)
associated with this article can be found, in the online version.
Table 7 shows the results for Me2N(CH2)2NH2-catalyzed
reactions of various aromatic aldehydes enhanced by silica gel at
50°C in CH3NO2. Aromatic aldehydes 3a, 3g-i, 3k, and 3l were
converted into the corresponding 1,3-dinitroalkanes 6a, 6g-i, 6k,
and 6l in good yields, respectively (entries 1 and 5-9).
Compounds 6 are known to be important building blocks for
various functionalized compounds such as 1,3-diamines,
heterocycles, and carbohydrate derivatives, and furthermore, for
biologically active substrates involving HIV-protease activity
inhibitors and NMDA receptor antagonists.31 In the cases of 3b
and 3f which possess electron-withdrawing groups on the
benzene ring, the yields of 6b and 6f were low because of the
formation of β-nitroalcohols 4b and 4f, respectively (entries 3
and 4). The decrease in the yields of 6b and 6f has been also
reported in the case of both primary and tertially amines-
immobilized silica-alumina.27
References and notes
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Yeung, T. H. W.; Huff, R.; Lindeman, S. V.; Dockendorff, C.
Tetrahedron 2016, 72, 3905-3916.
3. Allen, A. E.; MacMillan, D. W. Chem. Sci. 2012, 2012, 633-658.
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Silica gel and SBA-15 could be recycled five times without
any significant loss of activities for the synthesis of compounds
2a and 4a-6a (see Supplementary data).
In conclusion, we clarified that the amine-catalyzed nitroaldol
reactions were largely accelerated by the addition of silica gel or
SBA-15. Although it is impossible to reuse amines, solid acids
can be recycled without significant loss of activity. The synthesis
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Bigi, F. Tetrahedron Lett. 2001, 42, 2401-2403.
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