Synthesis of C, N-diaryl nitrones from the reduction of nitroarene with aromatic aldehydes promoted by metallic samarium

Article abstract of DOI:10.3184/030823407X218057

A mild and facile reduction of nitroarene with aromatic aldehydes promoted by metallic samarium to C, N-diaryl nitrones in moderate yields has been developed.

Full text of DOI:10.3184/030823407X218057

308 RESEARCH PAPER
MAY, 308–309
JOURNAL OF CHEMICAL RESEARCH 2007
Synthesis of C, N-diaryl nitrones from the reduction of nitroarene with
aromatic aldehydes promoted by metallic samarium
Xueshun Jia*, Dafeng Li, Qing Huang, Li Zhu and Jian Li
Department of Chemistry, Shanghai University, Shanghai 200444, P R China
A mild and facile reduction of nitroarene with aromatic aldehydes promoted by metallic samarium to C, N-diaryl
nitrones in moderate yields has been developed.
Keywords: C, N-diaryl nitrone, samarium, aromatic aldehyde, nitroarene
Nitrones are highly versatile synthetic intermediates1 and spin
trapping reagents used in biological systems.2 Nitrones are an
attractiveclassof1,3-dipoles, forthesynthesisofβ-lactamsand
other biologically interesting compounds.3 Various methods
for the synthesis of nitrones have been reported,4 including,
the condensation of aldehydes with hydroxylamines,4a the
oxidation of hydroxylamines, secondary amines or imines,4b-4e
the reaction of secondary amines with selenium dioxide,4f
and the thiazolium salt-catalysed reduction of nitrobenzene
with benzadehyde and triethylamine.4g A difficulty with these
methods is often the preparation of the starting materials or
catalysts. Some methods require expensive reagents or strong
oxidising agents.
The use of metallic samarium as a reducing agent in organic
synthesis has recently attracted attention.5 This is due to the
fact that metallic samarium is stable in air and has strong
reducing power (Sm3+/Sm = –2.41V). It is also cheap and
easy to handle. Recently, we have reported the reduction
and the C-acetylation of Baylis–Hillman adducts as well as
the acylation of alcohols with acyl chlorides promoted by
metallic samarium.6 We now report a facile reductive coupling
of nitroarenes with aromatic aldehydes promoted by metallic
samarium to give C, N-diaryl nitrones (Scheme 1).
Our initial experiment was carried out with nitrobenzene
(1.1 mmol) and benzaldehyde (1.0 mmol) as model substrates
with metallic samarium (2.0 mmol) at room temperature
without any other additives. However, no product was
observed with various solvents. When a catalytic amount
of acetic acid was added, a trace amount of desired nitrone was
observed with methanol as solvent. A series of experiments
were carried out in order to achieve the optimal conditions.
We were pleased to find that samarium (1.6 mmol) and
acetic acid (3.2 mmol) were sufficient to promote the present
conversion. It was also noteworthy that the reaction proceeded
smoothly without the exclusion of moisture or air.
On the other hand, a significant solvent effect was observed
in our experiments and methanol was found to be the best
choice. When acetonitrile, THF or dichloromethane were used
as solvent in this reaction, the desired nitrone was obtained
in 10–31% yields. Thus, the optimal reaction conditions were
established. A series of aromatic aldehydes were treated with
a nitroarene to give the corresponding products (Table 1).
All reactions proceeded smoothly and were finished within
0.5 hours.
Table 1 The reduction of nitroarene with aromatic aldehydes
promoted by metallic samarium
Entry
R
R’
Isolated yield/%
nitroarene
aldehyde
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
H
H
H
74
64
77
67
80
41
66
61
63
76
77
78
75
62
66
57
2-Cl
H
4-Cl
H
2, 4-Cl2
H
4-Me
H
4-MeO
H
3-MeO
H
4-tert-Bu
H
3, 4-(OCH2O)
H
Furan-2-carbaldehyde
4-Me
4-Me
4-Me
4-Me
4-Cl
4-Cl
H
4-Cl
4-Me
4-MeO
H
4-Cl
In summary, a mild and facile reduction of nitroarene with
aromatic aldehydes promoted by metallic samarium to give
C, N-diaryl nitrones in moderate yields has been developed.
The advantages of this protocol are single product, simple
manipulation, readily available starting materials and mild
condition.
Experimental
Melting points were determined on a capillary melting point apparatus
and were uncorrected. All reagents were commercially purchased and
used without further purification. All 1H NMR spectra were measured
in CDCl3 and recorded on Bruker AC – 500 (500 MHz) spectrometer
with TMS as the internal standard. 13C NMR spectra were measured
in CDCl3 and recorded on Bruker AC – 125(125 MHz) spectrometer
with TMS as the internal standard. IR spectra were measured with
a Perkin Elmer FT-IR-1600 spectrometer. Mass spectra were
determined with a HP 5989A mass spectrometer. Purification of
products was accomplished by preparative TLC.
General procedure
Nitroarene (1.1 mmol), aromatic aldehyde (1.0 mmol), methanol
(5 ml), acetic acid (3.2 mmol) and samarium powder (1.6 mmol) were
added successively to a round bottom flask containing a magnetic
stirrer bar. After being stirred at room temperature for 0.5 h, the
reaction mixture was quenched with saturated sodium bicarbonate
solution and extracted with dichloromethane. The extract was dried
O
NO2
R'
CHO
N
Sm/MeOH
HOAc, rt
R
+
R'
R
Scheme 1
* Correspondent.
PAPER: 07/4647

JOURNAL OF CHEMICAL RESEARCH 2007 309
over NaSO4. The solvent was removed under reduced pressure and
the residue was purified by preparative TLC on silica gel eluting with
petroleum ether/ethyl acetate to afford the corresponding C, N-diaryl
nitrones in moderate yields. The products were identified by m.p., IR,
1H NMR, 13C NMR, IR and mass spectra.
(d, J = 8.5 Hz, 2H), 7.87 (s, 1H), 8.29 (d, J = 8.5 Hz, 2H); IR (KBr)
ν: 3039, 2844, 1637, 1601, 1547, 1503, 1448, 1415, 1389, 1177, 1072,
841, 815, 751 cm-1.
n: 129 (lit.18 128.6–129.8°C); 1H NMR (CDCl3, TMS) δ: 2.41
(s, 3H), 3.88 (s, 3H), 6.99 (d, J = 9.0 Hz, 2H), 7.26 (d, J = 8.5 Hz,
2H), 7.66 (d, J = 8.5 Hz, 2H), 7.84 (s, 1H), 8.40 (d, J = 9.0 Hz, 2H);
IR (KBr) ν: 3045, 2922, 2852, 1645, 1600, 1557, 1507, 1460, 1417,
1392 1253, 1169, 1069, 826, 749 cm-1.
a: 111.2–111.5°C (lit.4d 112–113°C); 1H NMR (CDCl3, TMS)
δ: 7.47–7.49 (m, 6H), 7.77–7.79 (m, 2H), 7.93 (s, 1H), 8.39–8.40
(m, 2H); 13 C NMR (CDCl3, TMS) δ: 121.8, 128.7, 129.1, 129.2,
129.9, 130.7, 130.9, 134.6, 149.1; IR (KBr) ν: 3058, 1590, 1567,
1547, 1487, 1457, 1402, 1193, 1071, 843, 766 cm-1; MS (EI):
m/z (rel. intensity): 197 (M+, 10), 181 (5), 105 (16), 91 (100), 77 (43).
b: 82.1–82.5 (lit.7 81–82°C); 1H NMR (CDCl3, TMS) δ: 7.32–7.49
(m, 6H), 7.77–7.79 (m, 2H), 8.41 (s, 1H), 9.52–9.54 (dd, J = 2.0,
8.0 Hz, 1H); IR (KBr) ν: 3057, 1590, 1572, 1547, 1486, 1460, 1446,
1396, 1191, 1067, 889, 770 cm-1.
o: 164–166 (lit.16165.7–166.4°C); 1H NMR (CDCl3, TMS) δ: 7.46
(d, J = 9.0 Hz, 2H), 7.48–7.50 (m, 3H), 7.75 (d, J = 9.0 Hz, 2H),
7.90 (s, 1H), 8.37–8.39 (m, 2H); IR (KBr) ν: 3048, 2925, 1632, 1591,
1548, 1482, 1444, 1417, 1385, 1191, 1065, 819, 751 cm-1.
p: 137–138 (lit.19 137.9–138.8°C); 1H NMR (CDCl3, TMS)
δ: 7.45–7.47 (m, 4H), 7.30 (d, J = 9.0 Hz, 2H), 7.89 (s, 1H), 8.35 (d,
J = 9.0 Hz, 2H); IR (KBr) ν: 3092, 2923, 1633, 1588, 1544, 1485,
1417, 1399, 1172, 1073, 828 cm-1.
1
c: 154.9–155 (lit.8 156–158°C); H NMR (CDCl3, TMS) δ: 7.45
(d, J = 9.0 Hz, 2H), 7.47–7.51 (m, 3H), 7.76–7.78 (m, 2H), 7.91
(s, 1H), 8.36 (d, J = 9.0 Hz, 2H); IR (KBr) ν: 3059, 1592, 1574, 1548,
1485, 1461, 1445, 1397, 1192, 1068, 888, 771 cm-1.
Received 15 May 2007; accepted 6 June 2007
Paper 07/4647 doi: 10.3184/030823407X218057
d: 69.5–70.2 (lit.9 72°C); 1H NMR (CDCl3, TMS) δ: 7.39–7.53
(m, 5H), 7.77–7.79 (m, 2H), 8.38 (s, 1H), 9.54 (d, 1H); IR (KBr)
ν: 3069, 2922, 1627, 1598, 1580, 1537, 1484, 1385, 1189, 1089, 854,
749 cm-1.
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e: 89.8–90.5 (lit.10 91–93°C); H NMR (CDCl3, TMS) δ: 2.42 (s,
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f: 117.1–118.2°C (lit.11 116.6–117.8°C); H NMR (CDCl3, TMS)
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δ: 3.89 (s, 3H), 7.0 (d, J = 9.0 Hz, 2H), 7.43–7.50 (m, 3H), 7.76–7.79
(m, 2H), 7.86 (s, 1H), 8.41 (d, J = 9.0 Hz, 2 H); IR (KBr) ν: 2923,
1613, 1600, 1507, 1458, 1396, 1256, 1175, 1063, 846, 755 cm-1.
g: Oil;12 1H NMR (CDCl3, TMS) δ: 3.85 (s, 3H), 6.99–7.02
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7.66 (d, 1H), 7.74–7.76 (m, 2H), 7.91 (s, 1H), 8.37 (s, 1H); IR (KBr)
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756 cm-1.
h: Oil;13 1H NMR (CDCl3, TMS) δ: 1.36 (s, 9H), 7.45–7.49 (m,
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7.90 (s, 1H), 8.34 (d, J = 8.5 Hz, 2H); IR (KBr) ν: 2922, 1615, 1596,
1547, 1482, 1458, 1401, 1180, 1065, 840, 753 cm-1.
i: 134.5–135 (lit.14135°C); 1H NMR (CDCl3, TMS) δ: 6.05 (s, 2H),
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1H), 7.75–7.77 (m, 2H), 7.83 (s, 1H), 8.31 (s, 1H); IR (KBr) ν: 3057,
2893, 1655, 1617, 1595, 1550, 1486, 1452, 1393, 1266, 1192, 1106,
1073, 841, 761 cm-1.
j: 81.4–82.1 (lit.8 78–80°C); 1H NMR (CDCl3, TMS) δ: 6.64–6.66
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1H), 8.16 (s, 1H); IR (KBr) ν: 3097, 3055, 2926, 1654, 1595, 1568,
1543, 1473, 1388, 1296, 1156, 1070, 873, 769 cm-1.
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k: 123–124 (lit.15122.8–123.5°C); 1H NMR (CDCl3, TMS) δ: 2.42
(s, 3H), 7.27 (d, J = 8.5 Hz, 2H), 7.46–7.48 (m, 3H), 7.67 (d, J = 8.5 Hz,
2H), 7.91 (s, 1H), 8.38–8.40 (m, 2H); IR (KBr) ν: 3048, 2923, 1637,
1598, 1549, 1500, 1443, 1416, 1389, 1294, 1189, 1064, 815, 750 cm-1.
l: 167–167 (lit.16166.4–167.1°C); 1H NMR (CDCl3, TMS) δ:
2.42 (s, 3H), 7.27 (d, J = 9.0 Hz, 2H), 7.44 (d, J = 9.0 Hz, 2H), 7.65
(d, J = 8.5 Hz, 2H), 7.89 (s, 1H), 8.35 (d, J = 8.5 Hz, 2H); IR (KBr)
ν: 3051, 2920, 1665, 1592, 1545, 1502, 1482, 1419, 1399, 1193,
1075, 842, 820, 782 cm-1.
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m: 143–145 (lit.17 145.3–146.2°C); 1H NMR (CDCl3, TMS)
δ: 2.42 (s, 6H), 7.26 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 7.66
PAPER: 07/4647