Synthesis of some 2-aminonitroethanes via silica gel-catalyzed nitro-Mannich reaction

Article abstract of DOI:10.1515/znb-2006-0918

A direct one pot, three-component nitro-Mannich reaction of a nonenolizable aldehyde, aniline or one of its ring-substituted derivatives and nitromethane was carried out on silica gel surface. The products of the reaction, 2-aminonitroethane, were obtaine

Full text of DOI:10.1515/znb-2006-0918

Synthesis of Some 2-Aminonitroethanes via Silica Gel-Catalyzed
Nitro-Mannich Reaction
Ali S. Mahasneh
Department of Chemistry, Mutah University, PO. Box 7, Karak-Jordan
Reprint requests to Dr A. S. Mahasneh. E-mail: asmahasneh@hotmail.com
Z. Naturforsch. 61b, 1162 – 1165 (2006); received November 22, 2005
A direct one pot, three-component nitro-Mannich reaction of a nonenolizable aldehyde, aniline
or one of its ring-substituted derivatives and nitromethane was carried out on silica gel surface. The
products of the reaction, 2-aminonitroethane, were obtained in high yields. IR, 1H NMR, 13C NMR
spectra and elemental analysis confirmed the structures of the products.
Key words: Nitro-Mannich Reaction, Nonenolizable Aldehydes, Imines
◦
1)silica gel/60−70 C, 2−3h
Introduction
1
2
1
2
R CHO+R NH +CH NO −−−−−−−−−−−−−−−→R CH−NHR
2
3
2
+
2)H ,H
O
2
|
One of the earliest C-C bond formation reaction
methodologies was the Mannich reaction or more gen-
erally the α-aminoalkylation of carbonyl compounds.
The reaction involves an aldehyde, usually formalde-
hyde, the salt of an amine and a C-H acid, a ketone
or nitroalkane in a protic solvent such as ethanol. The
reaction mixture is then refluxed for several days af-
ter which the product is isolated in widely varying
yields [1]. The conventional Mannich reaction, how-
ever, has serious drawbacks such as drastic reaction
conditions (high temperature, long reaction time, and
use of protic solvents) all leading to undesirable by-
products.
In this paper, a one-pot three-component nitro-
Mannich type reaction catalyzed by silica is reported.
The reaction ocurred smoothly at mild conditions
giving high yields of 2-aminonitroethane products.
Similar products were obtained via a tin(II) chloride
mediated addition reaction of bromonitromethane to
imines [2]. Short reaction time, ease of handling the
reaction and low cost of substances are the advantages
of the described method here over other methods.
CH NO
2
2
1
2
3
Scheme 1.
Table 1. Yields of product 3.
3
a
b
c
d
e
f
R1
R2
Yield [%]
85
2-Methyl-C6H4
4-Ethyl-C6H4
3-Nitro-C6H4
C6H5
4-Hydroxy-C6H4
2,4-Dichloro-C6H3
4-Methoxy-C6H4
1-Naphthyl
2-Naphthyl
H
4-Bromo-C6H4
4-Nitro-C6H4
C6H5
4-Methyl-C6H4
C6H5
82
80
90
87
C6H5
77
g
h
i
4-Nitro-C6H4
C6H5
4-Bromo-C6H4
C6H5
4-Bromo-C6H4
4-Nitro-C6H4
4-Methyl-C6H4
83
78
87
j
95
k
l
H
H
H
90
92
m
88
The 1H NMR spectrum of product 3d shows a broad
signal at δ = 4.23 for the NH proton which could
be quenched with deuterium oxide, a doublet at δ =
4.72 (CH2NO2) and a triplet at δ = 5.30 (benzylic
CH). The 13C NMR spectrum showed characteristic
signals at δ = 56.8 (benzylic carbon) and 80.5 ppm
(CH2NO2). The compound showed a strong IR absorp-
Results and Discussion
2-Amino-1-nitroethanes 3 were obtained from alde- tion at 1552 cm−1 for the NO2 group. All other pre-
pared products gave H NMR, 13C NMR and IR sig-
1
hydes 1, anilines 2, and nitromethane on silica gel sur-
face in high yields (Scheme 1, Table 1). For example, nals consistent with the assigned structures.
when benzaldehyde, 4-methylaniline, nitromethane It has been generally known that the reaction
and silica gel were heated in a pressure tube for 80 min, pathways of the Mannich reaction depend on the
compound 3d was obtained in 90% yield.
nucleophilicity of substrate and the pH of the re-
c
0932–0776 / 06 / 0900–1162 $ 06.00 ꢀ 2006 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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A. S. Mahasneh · Synthesis of Some 2-Aminonitroethanes
1163
Experimental Section
All reagents were of commercial grade, and reagent qual-
ity solvents were used without further purification. IR spec-
tra were determined on a Mattson 5000 spectrometer. NMR
spectra were determined on Bruker AC 200 MHz instrument.
In all cases, samples were dissolved in CDCl3 using TMS as
internal standard. The elemental analysis was performed at
the Middle East Technical University Analyses Center.
Scheme 2.
General procedure for the synthesis of 3a – 3i
Into a pressure tube silica gel (0.50 g, Scharlau for thin
layer chromatography with gypsum and pigment addition
for UV) together with nitromethane (2.5 mmol) was intro-
duced. Aromatic aldehyde (2.5 mmol) and aniline or its
ring-substituted derivative (2.5 mmol) were also introduced.
When either the aldehyde or the aniline derivative or both
were solids they were boiled with THF (1 ml) and the solvent
was evaporated to dryness before silica gel and nitromethane
were added. The tube was then closed and immersed into an
oil bath where the temperature was kept at 60 – 70 ◦C. The
reaction was monitored by TLC, ethyl acetate / hexane mix-
ture 1 : 5 was used as eluent. It was found that the reaction
was about 80% complete after the first 20 min.
Scheme 3.
action medium [3]. The mechanism of the silica-
catalyzed nitro-Mannich reaction described here is not
known, however, a proposed mechanism, as shown in
After 2 – 3 h the contents of the tube were extracted with
ethyl acetate (30 ml). The extract was successively washed
Scheme 2, is suggested. This mechanism involves re- with 3×20 ml portions of 1 M HCl solution, saturated aque-
ous NaHCO3 (20 ml) solution and brine (20 ml). The so-
lution was then dried over anhydrous MgSO4. The solvent
was evaporated and the crude product was purified by col-
umn chromatography (silica gel, ethyl acetate / hexane mix-
ture 1 : 4 as eluent).
action of nitromethane or its aci-nitro (nitronic) acid
form with the Si = O double bond at the surface of sil-
ica as a first step [4]. A nucleophilic attack of the prod-
uct on imine or imonium ions that are formed during
the course of the reaction to give product 3 and regen-
erates the catalyst is the second step.
An alternative mechanism involving two steps could
also be proposed Scheme 3. The first step is a
silicagel-catalyzed aldol-type condensation forming
General procedure for the synthesis of 3j – 3m
Paraformaldehyde (2.5 mmol), aniline or its ring-
substituted derivative (2.5 mmol) and dry THF (1 ml) were
nitrostyrene and addition of amine to the latter to form boiled in a pressure tube until no solid was observed. Silica
gel 0.50 g and nitromethane (2.5 mmol) were introduced. The
tube was closed and immersed in an oil bath at 60 – 70 ◦C.
The reaction was completed as before and also the workup
and purification procedures were similar.
product 3 in the second step.
Conclusion
As can be seen from the results the method de-
scribed here can be considered as an efficient method
for this kind of C-C bond formation reaction. Func-
tionalities present in the products may be suitable for
a wide range of other chemical manipulations. The
CH2NO2 unit, for example, can be transformed into
a carbonyl group by the Nef reaction [5], and then to
carboxylic acid, making products 3 precursors to some
α-amino acids. The feasibility of replacing the nitro
group by hydrogen atom (denitration) using tributyltin
hydride is also important [6].
2-(4-Bromoanilino)-2-(2-methylphenyl)-1-nitroethane
(3a): M. p. 101 – 103 ◦C. – IR (KBr): ν = 3399 (N-H), 3073,
3019, 2920, 1591, 1547 (NO2), 1495, 1381, 1256, 1182,
1072 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 2.48 (s,
3H, Me), 4.38 (broad, 1H, NH), 4.61 (m, 2H, CH2NO2),
5.30 (m, 1H, o-CH3-C6H4CH), 6.32 – 7.42 (m, 8H, Ar). –
13C{H} NMR (200 MHz, CDCl3): δ = 19.3 (Me), 53.3
(o-CH3-C6H4CH), 78.3 (CH2NO2), 110.5, 115.2, 125.2,
127.0, 128.8, 131.3, 132.0, 134.8, 135.4, 144.4 (Ar). –
C15H15N2O2Br (335.20): calcd. C 53.74, H 4.51, N 8.36;
found C 53.61, H 4.55, N 8.40.
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1164
A. S. Mahasneh · Synthesis of Some 2-Aminonitroethanes
2-(4-Nitroanilino)-2-(4-ethylphenyl)-1-nitroethane (3b): calcd. C 54.06, H 3.89, N 9.00; found C 54.11, H 3.90,
M. p. 96 – 97 ◦C. – IR (KBr): ν = 3399 (N-H), 3329, N 9.11.
2962, 2929, 2898, 1601, 1554 (NO2), 1477, 1300, 1184,
1111 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 1.21
(t, 3J = 4 Hz, 3H, CH3CH2), 2.63 (q, 3J = 4 Hz, 2H,
CH3CH2), 4.80 (m, 2H, CH2NO2), 5.31 (m, 1H, p-C2H5-
C6H4CH), 5.72 (broad, 1H, NH), 6.53 – 8.8 (m, 8H, Ar).
2-(4-Nitroanilino)-2-(4-methoxyphenyl)-1-nitroethane
(3g): M. p. 115 – 117 ◦C. – IR (KBr): ν = 3383 (N-H), 1601,
1554 (NO2), 1309, 1251, 1178, 1113 cm−1. – 1H NMR
(200 MHz, CDCl3): δ = 3.78 (s, 3H, OCH3), 4.50 (broad,
1H, NH), 4.75 (d, 2H, 3J = 5 Hz, 2H, CH2NO2), 5.25 (q,
1H, 3J = 5 Hz, CH3O-C6H4CH), 6.6.52 – 8.22 (4 d, 8H, Ar).
–
13C{H} NMR (200 MHz, CDCl3): δ = 15.5 (CH3CH2),
–
13C{H} NMR (200 MHz, CDCl3): δ = 55.1 (OCH3), 55.2
28.8 (CH3CH2), 56.0 (p-C2H5-C6H4CH), 80.0 (CH2NO2),
112.5, 113.3, 126.1, 126.3, 129.5, 133.0, 145.5, 151.8 (Ar).
– C16H17N3O4(315.32): calcd. C 60.94, H 5.43, N 13.33;
found C 60.77, H 5.45, N 13.42.
(CH3O-C6H4CH), 79.8 (CH2NO2), 112.8, 115.0, 121.5,
128.0, 131.5, 139.8, 151.4, 160.2 (Ar). – C15H15N3O5
(317.29): calcd. C 56.68, H 4.77, N 13.24; found C 56.55,
H 4.82, N 13.20.
2-Anilino-2-(3-nitrophenyl)-1-nitroethane (3c): M. p.
126 – 128 ◦C (lit. 127 – 128 ◦C). – IR (KBr): ν = 3404
(N-H), 2924, 2854, 1602, 1554, 1529 (NO2), 1352, 1313,
1293 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 4.63
(broad, 1H, NH), 4.72 (d,3J = 4 Hz, 2H, CH2NO2), 5.28
(q, 3J = 4 Hz, 1H, C6H4CH), 6.50 – 8.32 (m, 9H, Ar). –
13C{H} NMR (200 MHz, CDCl3): δ = 56.0 (C6H4CH),
79.7 (CH2NO2), 114.0, 119.6, 122.0, 124.0, 129.5, 130.2,
132.9, 140.2, 145.0, 149.0 (Ar). – C14H13N3O4 (287.27):
calcd. C 58.53, H 4.56, N 14.63; found C 58.44, H 4.47,
N 14.66.
2-◦Anilino-2-(1-naphthyl)-1-nitroethane (3h): M. p. 111 –
112 C. – IR (KBr): ν = 3387 (N-H), 3065, 2916, 1602,
1554 (NO2), 1512, 1425, 1373, 1315, 1265 cm−1. – 1H NMR
(200 MHz, CDCl3): δ = 4.55 (broad, 1H, NH), 4.8 (m,
2H, CH2NO2), 6.05 (m, 1H, C10H7CH), 6.50 – 8.25 (m,
12H, Ar). – 13C{H} NMR (200 MHz, CDCl3): δ = 52.8
(C10H7CH), 79.5 (CH2NO2), 113.7, 119.2, 121.8, 124.0,
125.8, 126.5, 127.5, 129.0, 129.1, 129.7, 130.8, 132.5, 134.0,
145.5 (Ar). – C18H16N2O2 (292.33): calcd. C 73.95, H 5.52,
N 9.58; found C 73.88, H 5.48, N 9.62.
2-(4-Methylanilino)-2-phenyl-1-nitroethane (3d): M. p.
2-(4-Bromoanilino)-2-(2-naphthyl)-1-nitroethane
M. p. 111 – 112 ◦C – IR (KBr): ν = 3408 (N-H), 2924,
2852, 1595, 1553 (NO2), 1498, 1377, 1330, 1082 cm−1
1H NMR (200 MHz, CDCl3): δ = 4.60 (broad, 1H,
NH), 4.78 (m, 2H, CH2NO2), 5.30 (m, 1H, C10H7CH),
6.45 – 79.2 (m, 11 H, Ar). – 13C{H} NMR (200 MHz,
CDCl3): δ = 57.2 (C10H7CH), 80.0 (CH2NO2), 110.8,
115.5, 123.9, 126.0, 126.8, 128.0, 128.0, 128.2, 129.9,
142.2, 133.3, 134.7, 139.5, 145.0 (Ar). – C18H15N2O2Br
(371.22): calcd. C 58.24, H 4.07, N 7.55; found C 58.33,
H 4.10, N 7.48.
(3i):
◦
◦
83 – 84 C (lit. 82 – 84 C) – IR (KBr): ν = 3409 (N-H),
3028, 2920, 1618, 1552 (NO2), 1520, 1452, 1379, 1302,
1259 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 2.25 (s,
3H, Me), 4.23 (broad, 1H, NH), 4.72 (d, 3J = 5 Hz, 2H,
CH2NO2), 5.30 (t, 3J = 5 Hz, 1H, C6H5CH), 6.35 – 7.50 (m,
9H, Ar). – 13C{H} NMR (200 MHz, CDCl3): δ = 20.5 (Me),
56.8 (C6H5CH), 80.5 (CH2NO2), 114.0, 126.5, 128.8, 129.5,
130.0, 132.0, 138.0, 143.8 (Ar). – C15H16N2O2 (256.29):
calcd. C 70.29, H 6.29, N 10.93; found C 70.33, H 6.32,
N 10.88.
.
–
2-Anilino-2-(4-hydroxyphenyl)-1-nitroethane (3e): M. p.
109 – 110 ◦C. – IR (KBr): ν = 3410 (N-H), 3379 (OH), 2924,
2845, 1604, 1541 (NO2), 1504, 1431, 1384, 1315, 1295,
1222, 1129 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 3.72
(broad, 1H, NH), 4.35 (s, 1H, OH), 4.72 (d, 3J = 5 Hz, 2H,
CH2NO2), 5.21 (m, 1H, C6H4CH), 6.6 – 8.12 (m, 9H, Ar).
2-Anilino-1-nitroethane (3j): Oil. – IR (KBr): ν = 3400
(N-H), 2924, 2854, 1602, 1550 (NO2), 1510, 1427, 1384,
1317, 1257 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 3.75
(t, 3J = 4.0 Hz, 2H, NHCH2), 4.06 (broad, 1H, NH), 4.55
3
(t, J = 4.0 Hz, 2H, CH2NO2), 6.57 – 7.30 (m, 5 H, Ar). –
13C{H} NMR (200 MHz, CDCl3): δ = 41.5 (NHCH2), 74.2
(CH2NO2), 113.0, 119.0, 129.4, 146.5 (Ar). – C8H10N2O2
(166.18): calcd. C 57.82, H 6.07, N 16.86; found C 57.77,
H 6.10, N 16.77.
–
13C{H} NMR (200 MHz, CDCl3): δ = 56.1 (C6H4CH),
80.3 (CH2NO2), 113.8, 116.0, 116.5, 119.0, 128.0, 129.3,
132.0, 139.2 (Ar). – C14H14N2O3 (258.27): calcd. C 65.10,
H 6.46, N 10.85; found C 65.44, H 6.32, N 10.89.
2-(4-Bromoanilino)-1-nitroethane (3k): M. p. 41 – 42 ◦C.
2-Anilino-2-(2,4-dichlorophenyl)-1-nitroethane
(3f): – IR (KBr): ν = 3400 (N-H), 2854, 1593, 1537 (NO2),
M. p. 112 – 114 ◦C. – IR (KBr): ν = 3402 (N-H), 3055, 1498, 1427, 1358, 1317, 1248, 1180 cm−1. – 1H NMR
2924, 1605, 1554 (NO2), 1504, 1423, 1379, 1311, 1263, (200 MHz, CDCl3): δ = 3.77 (t, 3J = 4.7 Hz, 2H, NHCH2),
1101, 1045 cm−1. – 1H NMR (200 MHz, CDCl3): δ = 4.20 4.16 (broad, 1H, NH), 4.57 (t, 3J = 4.7 Hz, 2H, CH2NO2),
(broad, 1H, NH), 4.70 (m, 2H, CH2NO2), 5.53 (m, 1H, 6.57, 7.30 (2 d, 3J = 8.5 Hz, 4 H, Ar). – 13C{H} NMR
2,4-Cl2-C6H3CH), 6.54 – 7.53 (m, 8H, Ar). – 13C{H} NMR (200 MHz, CDCl3): δ = 41.1 (NHCH2), 74.4 (CH2NO2),
(200 MHz, CDCl3): δ = 53.1 (2,4-Cl2-C6H3CH), 78.5 110.7, 114.8, 132.4, 146.0 (Ar). – C8H9N2O2Br (245.07):
(CH2NO2), 114.0, 119.5, 121.2, 128.0, 129.1, 129.4, 129.5, calcd. C 39.21, H 3.70, N 11.43; found C 39.27, H 3.74,
133.5, 135.2, 145.0 (C6H4). – C14H12N2O2Cl2(311.15): N 11.47.
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A. S. Mahasneh · Synthesis of Some 2-Aminonitroethanes
2-(4-Nitroanilino)-1-nitroethane (3l): M. p. 82 – 83 ◦C.
1165
2-(4-Methylanilino)-1-nitroethane (3m): M. p. 72 – 73 ◦C.
– IR (KBr): ν = 3371 (N-H), 1628, 1547 (NO2), 1479, – IR (KBr): ν = 3396 (N-H), 2922, 1614, 1537 (NO2),
1284, 1182, 1111 cm−1. – 1H NMR (200 MHz, CDCl3): 1427, 1356, 1319, 1251, 1197 cm−1. – 1H NMR (200 MHz,
δ = 3.92 (t, 3J = 4.7 Hz, 2H, NHCH2), 4.14 (broad, CDCl3): δ = 2.23 (s, 3 H, Me), 3.78 (t, 3J = 4.7 Hz,
3
1H, NH), 4.65 (t, 3J = 4.7 Hz, 2H, CH2NO2), 6.60, 2H, NHCH2), 3.95 (broad, 1H, NH), 4.58 (t, J = 4.7 Hz,
8.12 (2 d, 3J = 8.5 Hz, 4 H, Ar). – 13C{H} NMR 2H, CH2NO2), 6.58, 7.30 (2 d, 3J = 8.5 Hz, 4 H, Ar). –
(200 MHz, CDCl3): δ = 40.5 (NHCH2), 74.0 (CH2NO2), 13C{H} NMR (200 MHz, CDCl3): δ = 20.6 (Me), 41.5
111.7, 114.5, 127.0, 148.0 (Ar). – C8H9N3O4 (221.18): (NHCH2), 74.3 (CH2NO2), 114.8, 128.0, 129.70, 143.0 (Ar).
calcd. C 45.50, H 4.30, N 19.89; found C 45.44, H 4.27, – C8H12N2O2 (180.20): calcd. C 59.99, H 6.71, N 15.55;
N 19.77.
found C 59.85, H 6.73, N 15.45.
[4] B. M. Salim, S. M. Khalil, Z. Naturforsch. 60a, 47
(2005).
[5] P. Ceccherelli, M. Curini, M. C. Marcotullio,
F. Epifano, O. Rosati, Synth. Commun. 28, 3057
(1998).
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