Configuration-specific reaction of nitric oxide with aldehyde arylhydrazones

Article abstract of DOI:10.1002/cjoc.201090207

Reactions of aldehyde arylhydrazones (1) with nitric oxide in the presence of trace oxygen gave exclusively (E)-C(1')-nitrohydrazones (2) in high yield. The structure of products was confirmed by NMR, IR, MS and X-ray crystallography. The reaction is assu

Full text of DOI:10.1002/cjoc.201090207

FULL PAPER
Configuration-Specific Reaction of Nitric Oxide with Aldehyde
Arylhydrazones
Yang, Desuo*,a,b(杨得锁)
Zhu, Haiyuna(朱海云)
Wu, Longminb(吴隆民)
Guo, Yaninga(郭亚宁)
a Department of Chemistry & Engineering, Baoji University of Arts & Science, Baoji, Shaanxi 721013, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
Reactions of aldehyde arylhydrazones (1) with nitric oxide in the presence of trace oxygen gave exclusively
(E)-C(1')-nitrohydrazones (2) in high yield. The structure of products was confirmed by NMR, IR, MS and X-ray
crystallography. The reaction is assumed to be initiated by addition of NO2 to the imine double.
Keywords nitric oxide, hydrazones, electrophilic, addition, configuration-specific
Introduction
NO in biochemistry and our ongoing studies on the re-
action of NO with arylhydrazones, we have examined
the reaction of NO with aldehyde arylhydrazones (1) in
the presence of trace oxygen in CH2Cl2 at room tem-
perature [Eq. (1)]. The unique products, (E)-C(1')-ni-
trohydrazones (2), instead of the azo-compounds from
ketone arylhydrazones,9 were obtained in high yield.
Their (Z)-isomers were not detected. These results indi-
cated that the reaction of NO with 1 occurred in a dif-
ferent mechanism, compared to those of ketone
arylhydrazones. We assume that the π-bond of
imino-group breaks in the course of reaction, and forms
a rotation-free C—N single bond, which afresh con-
structs a C＝N double bond through an elimination re-
action.
Nitric oxide (NO) is a key cell signaling molecule in
many biological processes such as vasodilatation, neu-
rotransmission, microbial and tumor-related cell death,
tissue damage, and organ-specific autoimmune disor-
ders.1 Thus, the proper regulation of NO levels is pro-
posed as a desirable target for developing new medi-
cines.2 In addition, intensive researches have been di-
rected toward reactions of NO with biological mole-
cules3 and various organic molecules such as amides,4
oximes,5 Wittig reagents,6 Schiff bases,7 arylhydrazi-
nes,8 ketone hydrazones,9 chiral (E)-(S)-2-(benzylidene-
amino)ethanols,10 dihydropyrimidinones,11 2,3-epoxy-
phenyl ketones,12 N-tosyl aziridines,13 enantiopure ep-
oxides,14 etc. The imine double bond of hydrazones was
found to be cleaved exclusively in the reaction of ketone
hydrazones with NO, giving mono-nitrated azo-com-
pounds.9
Arylhydrazones have long been utilized for analyz-
ing carbonyl compounds. In recent years, some of them
and their complexes were found to have the anticancer
properties.15 In particular, hydrazones have been used to
establish chiral configurations and certain specific
skeletons.16 Moon17 studied the bromination and chlori-
nation of hydrazones, and obtained the corresponding
azo-compounds. The resulting C(1')-halogenated hy-
drazones were unstable intermediates before they con-
verted into the final products. Guo et al.18 obtained a
parallel conclusion that the halogenation of hydrazones
was an electrophilic reaction at C(1')-atom and the con-
version of halogenated hydrazones to azo-compounds
underwent a prototropic reaction.
Experimental
All solvents were distilled prior to use according to
standard procedures. Methylene dichloride was dehy-
drated with CaH2 by refluxing. (E)-Aldehyde hydra-
zones (1) were prepared and purified according to the
literature procedure,19 and characterized by NMR, MS,
and IR.
1H and C NMR spectra were recorded on a Bruker
13
Avance 400 (1H: 400 MHz, 13C: 100 MHz, δ downfield
from TMS). IR analysis was performed on a Nicolet
NEXUS 670 FT-IR. Mass data were obtained on a
As part of continuing efforts to explore the role of
*
E-mail: yangds09@163.com; Tel.: 0086-0917-3566508; Fax: 0086-0917-3565255
Received October 11, 2009; revised February 19, 2010; accepted March 18, 2010.
Project supported by the National Natural Science Foundation of China (No. 20572040) and Shaanxi Provincial Natural Science Foundation
of China (No.2009K01-51).
Chin. J. Chem. 2010, 28, 1193— 1198
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Yang et al.
FULL PAPER
HP-5988A GC-MS, and HR-ESI-MS data on a Bruker
Daltonics APEx II FT-ICR. Melting points were deter-
mined with an XT4-100X micro-melting point apparatus
and not corrected.
purified by column chromatography on silica-gel
(200—300 mesh, ethyl acetate-hexane: 1∶5, V∶V),
giving the pure product 2 (Table 1).
(E)-N-(2,4-Dinitrophenyl)-N'-(1-nitroethylidene)-
hydrazine (2a) Yellow needles, m.p. 143—144 ℃;
1H NMR (CDCl3, 400 MHz) δ: 2.66 (s, 3H), 8.17 (d,
J＝9.2 Hz, 1H), 8.44 (dd, J＝2.8, 9.2 Hz, 1H), 9.17 (d,
J＝2.8 Hz, 1H), 11.11 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ: 30.8, 117.9, 122.7, 130.5, 132.4, 141.0, 143.3,
150.3; IR (KBr) ν: 3293 (NH), 3102, 1618, 1599, 1540,
1502, 1430, 1345, 1317, 1283, 1221, 1178, 1134, 1059,
X-ray analysis on single crystals was carried out at
293(2) K on a Nonius CAD4 automatic diffractometer
using Mo Kα radiation (λ＝0.71073 Å) graphite mono-
chromation. Structural solutions and full-matrix
least-squares refinements based on F2 were performed
with the SHELXS 97 and SHELXL-97 program pack-
ages, respectively. All the non-hydrogen atoms were
anisotropically positioned. Hydrogen atoms were placed
at geometrical positions and constrained to ride on their
parent atoms. Analytical expressions of neutral-atom
scattering factors were employed, and anomalous dis-
persion corrections were incorporated. The crystallo-
graphic data (excluding structure factors) have been
deposited at the Cambridge Crystallographic Data Cen-
ter.
－1
917, 872, 844, 742, 688＋, 598, 466 cm . HR-ESI-MS
calcd for C8H7N5O6 (M ) 269.0391, found 269.0393.
EIMS (70 eV) m/z: 269 (M＋), 181, 135, 78, 63, 51, 43.
(E)-N-(2,4-Dinitrophenyl)-N'-(1-nitrobutylidene)-
hydrazine (2b) Yellow needles, m.p. 120 ℃ (de-
1
comp.); H NMR (CDCl3, 400 MHz) δ: 1.13 (t, J＝7.6
Hz, 3H), 1.85 (q, J＝7.6 Hz, 2H), 3.03 (t, J＝7.6 Hz,
2H), 8.17 (d, J＝9.6 Hz, 1H), 8.50 (dd, J＝2.8, 9.6 Hz,
1H), 9.16 (d, J＝2.8 Hz, 1H), 11.28 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ: 14.0, 18.8, 27.5, 117.9, 122.8,
130.6, 140.8, 143.4, 154.0; IR (KBr) ν: 3290 (NH),
3101, 2967, 2874, 1619, 1598, 1532, 1503, 1452, 1427,
1345, 1319, 1274, 1219, 1167, 1133, 912, 848, 739, 610
General procedure for the synthesis of 2a— 2j
Compound 1 (0.5 mmol) was dissolved in 100 mL of
anhydrous methylene dichloride to give its stock solu-
tion. NO was produced by dropwise addition of 1 mol•
－1
－1
cm . HR-ESI-MS calcd for C10H15N6O6 (M＋ NH＋4 )
L
H2SO4 solution to a stirred saturated aqueous solu-
tion of NaNO2 under an argon atmosphere. NO gas was
purified by passing it through a series of scrubbing bot-
285.1052, found 285.1055. EIMS (70 eV) m/z: 297
(M＋), 268, 206, 195, 71, 43.
－1
tles containing 4 mol•L NaOH, ditilled water, and
X-ray crystallography data for 2b C10H11N5O6,
Mr＝297.24, monocinic, space group P2(1)/c with cell
dimension of a＝1.2284(2) nm, b＝1.7594(3) nm, c＝
anhydrous CaCl2 pellets in this order. Bottles were still
under an argon atmosphere. The purified NO was bub-
bled through a stirred stock solution of compound 1,
which was previously degassed by argon for ca. 5—10
min and kept at a pressure of up to ＋10 mm H2O col-
umn over local atmospheric pressure, at ambient tem-
perature for 8—16 h. In the course of reaction, the argon
flow rate was controlled by regulating the flow meter at
0.61338(7) nm, β＝94.67(1)°, V＝1.3213(3) nm3, Z＝4,
－1
ρ
calcd＝1.494 g/cm3, µ＝1.26 cm . F(000)＝616, 3.32°
≤2θ≤50.98°, －14≤h≤14, －21≤k≤0, 0≤l≤7.
2991 data collected, 2461 unique data (Rint＝0.0112).
1599 data with I ＞ 2σ(I), 192 refined parameters,
GOF(F2)＝0.954, R1＝0.0594, wR2＝0.0891. The crys-
tallographic data have been deposited at the Cambridge
Crystallographic Data Center as Supplementary Publi-
cation No. CCDC-212522.
－1
0.8 L•min . The total amount of NO passing through
the solution was estimated to be roughly 1000 mmol at
the local atmosphere pressure using the ideal gas law.
The progress of reaction was monitored by TLC. After
the completion of reaction, the mixture was dried over
anhydrous MgSO4, concentrated under vacuum, and
(E)-N-(2,4-Dinitrophenyl)-N'-(3-methyl-1-nitro-
butylidene)hydrazine (2c) Yellow needles, m.p. 123
Table 1 Reaction of NO with 1 in CH2Cl2
R1
Entry
Hydrazone
R
R2
Timea/h
Yield of 2b/%
1
2
1a
1b
1c
1d
1e
1f
CH3
NO2
NO2
NO2
NO2
NO2
NO2
NO2
H
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
NO2
8
94
96
96
94
95
93
94
91
90
94
n-C3H7
8
3
i-C4H9
8
4
i-C3H7
10
10
12
13
12
16
10
5
p-Methoxyphenyl
Phenyl
6
7
1g
1h
1i
p-Chlorophenyl
Phenyl
8
9
p-Nitrophenyl
3,4-Dimethoxyphenyl
NO2
NO2
10
1j
a The reaction time (h). b Yield of the isolated product.
1194
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1193— 1198

Configuration-Specific Reaction of Nitric Oxide with Aldehyde Arylhydrazones
1
—124 ℃; H NMR (CDCl3, 400 MHz) δ: 1.22 (d, J＝
7.2 Hz, 6H), 2.25 (m, 1H), 2.95 (d, J＝7.2 Hz, 2H), 8.17
(d, J＝9.6 Hz, 1H), 8.49 (dd, J＝2.8, 9.6 Hz, 1H), 9.18
(d, J＝2.8 Hz, 1H), 11.32 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ: 22.6, 27.0, 34.4, 117.9, 122.8, 130.6, 132.2,
140.8, 143.4, 153.7; IR (KBr) ν: 3299 (NH), 3099, 2965,
2930, 2872, 1615, 1596, 1537, 1498, 1449, 1425, 1334,
354.0448. EIMS (70 eV) m/z: 331 (M＋), 238, 222, 193,
182, 164, 105, 77.
(E)-N-(2,4-Dinitrophenyl)-N'-[(4-chlorophenyl)-1-
nitromethylene]hydrazine (2g) Yellow needles, m.p.
1
120—122 ℃; H NMR (CDCl3, 400 MHz) δ: 7.53 (d,
J＝11.2 Hz, 2H), 7.73 (d, J＝11.2 Hz, 2H), 8.24 (d, J＝
11.2 Hz, 1H), 8.52 (dd, J＝2.0, 13.2 Hz, 1H), 9.10 (d,
J＝2.0 Hz, 1H), 11.26 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ: 118.1, 121.8, 122.8, 129.2, 130.2, 130.6, 130.7,
132.5, 139.3, 141.2, 142.9, 149.7. EIMS (70 eV) m/z:
365 (M＋), 336, 290, 274, 256, 227, 164, 156, 139, 111,
75.
－1
1220, 1179, 1334, 1061, 918, 849, 740, 688, 599 cm .
HR-ESI-MS calcd for C11H11N5O6 (M＋ ) 300.0865,
found 300.0865.
(E)-N-(2,4-Dinitrophenyl)-N'-(2-methyl-1-nitro-
propylidene)hydrazine (2d) Yellow needles, m.p.
1
119—121 ℃; H NMR (CDCl3, 400 MHz) δ: 1.35 (d,
(E)-N-(4-Nitrophenyl)-N'-(nitro-phenyl-methylene)-
1
J＝6.8 Hz, 6H), 3.49 (d, J＝6.8 Hz, 1H), 8.13 (d, J＝
9.6 Hz, 1H), 9.47 (dd, J＝2.4, 9.6 Hz, 1H), 9.16 (d, J＝
2.4 Hz, 1H), 11.32 (s, 1H); 13C NMR (CDCl3, 100 MHz)
δ: 20.2 (×2), 30.7, 117.2, 122.9, 130.1, 132.4, 140.9,
143.4, 146.2; IR (KBr) ν: 3243 (NH), 3117, 3092, 2991,
2876, 1611, 1589, 1548, 1492, 1411, 1333, 1299, 1253,
hydrazine (2h) Red needle, m.p. 112—114 ℃; H
NMR (CDCl3, 400 MHz) δ: 7.16—7.60 (m, 7H), 8.18 (d,
J＝12.0 Hz, 2H), 11.73 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ: 124.1, 124.9, 129.0, 129.9, 130.5, 135.0, 150.1,
154.5, 181.3; IR (KBr) ν: 3434, 3265, 1595, 1570, 1497,
1445, 1409, 1340, 1248, 1176, 1106, 1003, 968, 850,
766, 747, 688, 6＋20 cm － 1. HRESIMS calcd for
C13H10N4O4 (M＋H ) 287.0775, found 287.0786. EIMS
(70 eV) m/z: 286 (M＋), 257, 239, 194, 167, 149, 105,
77.
－
1
1164, 1132, 1083, 1049, 916, 880, 692 cm ＋
.
HR-ESI-MS calcd for C10H15N6O6 (M ＋ NH4
)
285.1052, found 285.1060. EIMS (70 eV) m/z: 297
(M＋), 190, 181, 77, 75, 71, 63, 43, 41, 39.
(E)-N-(2,4-Dinitrophenyl)-N'-[(4-methoxyphenyl)-
nitromethylene]hydrazine (2e) Red needles, m.p.
(E)-N-(2,4-Dinitrophenyl)-N'-[(4-nitrophenyl)-1-
nitromethylene]hydrazine (2i) Yellow needles, m.p.
1
1
115—116 ℃. H NMR (CDCl3, 400 MHz) δ: 3.94 (s,
164 ℃ (decomp); H NMR (CDCl3, 400 MHz) δ:
3H), 7.18 (d, J＝9.6 Hz, 2H), 7.44 (d, J＝9.6 Hz, 2H),
8.24 (d, J＝9.6 Hz, 1H), 8.48 (d, J＝2.4, 9.6 Hz, 1H),
9.11 (d, J＝2.4 Hz, 1H), 11.38 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ: 55.6, 115.0, 115.6, 115.9, 122.7,
130.4, 130.5, 132.2, 140.7, 143.2, 151.3, 162.7; IR (KBr)
ν: 3253 (NH), 3101, 2975, 2929, 1615, 1598, 1541,
1505, 1429, 1352, 1312, 1265, 1228, 1172, 1136, 1113,
7.72 (d, J＝8.8 Hz, 2H), 8.22 (d, J＝9.6 Hz, 1H),
8.33—8.52 (m, 3H), 9.06 (d, J＝2.4 Hz, 1H), 11.28 (s,
1H); 13C NMR (CDCl3, 100 MHz) δ: 118.0, 122.6,
123.7, 125.1, 129.7, 130.5, 130.6, 132.8, 141.5, 142.4,
149.8; IR (KBr) ν: 3276, 3104, 2847, 1615, 1598, 1536,
1520, 1500, 1439, 1343, 1316, 1222, 1143, 1118, 1024,
－1
1007, 909, 850, 812, 740,＋706, 692, 618, 557 cm .
－1
1018, 996, 830 cm . HR-ESI-MS calcd for C14H15-
EIMS (70 eV) m/z: 376 (M ), 343, 311, 279, 195, 167,
149, 69, 57, 43.
N6O7 (M＋ NH＋4 ) 379.0997, found 379.1006. EIMS (70
eV) m/z: 361 (M＋), 298, 282, 269, 252, 223, 135.
(E)-N-(2,4-Dinitrophenyl)-N'-[(3,4-dimethoxy-
phenyl)-1-nitromethylene]hydrazine (2j) Red nee-
dles, m.p. 128—130 ℃; 1H NMR (CDCl3, 400 MHz) δ:
3.94 (s, 3H), 4.01 (s, 3H), 6.96 (d, J＝2.4 Hz, 1H), 7.16
—7.19 (m, 2H), 8.24 (d, J＝12.8 Hz, 1H), 8.48 (dd, J＝
2.8, 12.8 Hz, 1H), 9.11 (d, J＝2.8 Hz, 1H) 11.45 (s, 1H);
13C NMR (CDCl3, 100 MHz) δ: 31.2, 56.4, 111.1, 112.1,
115.2, 117.5, 118.3, 122.6, 123.1, 130.7, 132.7, 141.1,
143.5, 150.6, 152.9; IR (KBr) ν: 3270, 3089, 2962, 2936,
X-ray crystallography data for 2e C14H11N5O7,
Mr＝361.28, monocinic, space group P2(1)/c with cell
dimension of a＝1.5075(2) nm, b＝1.7683(3) nm, c＝
0.6099(3) nm, β＝100.43(1)°, V＝1.5990(4) nm3, Z＝4,
－1
ρcalcd＝1.501 g/cm3, µ＝1.23 cm . F(000)＝744, 2.74°
≤2θ≤50.50°, －18≤h≤17, －21≤k≤0, 0≤l≤7.
3199 data collected, 2898 unique data (Rint＝0.0118),
1578 data with I ＞ 2σ(I), 237 refined parameters,
GOF(F2)＝1.027, R1＝0.0547, wR2＝0.1626. The crys-
tallographic data have been deposited at the Cambridge
Crystallographic Data Center as Supplementary Publi-
cation No. CCDC-224158.
2841, 1618, 1594, 1542, 1509, 1452, 1427, 1342, 13－16,
1
1263, 1202, 1170, 1138, 1013, 912, 846 cm
.
HR-ESI-MS calcd for C15H13N4O8 (M＋－H) 390.0691,
found 390.0682. EIMS (70 eV) m/z: 391 (M＋), 362, 300,
202, 165, 77.
(E)-N-(2,4-Dinitrophenyl)-N'-(nitro-phenyl-meth-
ylene)hydrazine (2f) Yellow needles, m.p. 125—126
℃; 1H NMR (CDCl3, 400 MHz) δ: 7.53—7.73 (m, 5H),
8.24 (d, J＝8.8 Hz, 1H), 8.51 (dd, J＝8.8, 1.6 Hz, 1H),
9.11 (d, J＝1.6 Hz, 1H), 11.32 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ: 117.9, 122.7, 123.6, 128.6, 130.1,
130.4, 132.4, 132.7, 141.0, 143.0; IR (KBr) ν: 3269,
3100, 1616, 1596, 1541, 1497, 1430, 13－45, 1318, 1215,
Results and discussion
Results for the reaction of NO with 1 are summa-
rized in Table 1. As seen from Table 1, there was a sub-
stituent effect on the reaction. The properties of R group
affected the facility of the nitro substitution and hence
controlled the rate of reaction. When R in 1 was an alkly
group, the time needed for reaction completion became
1
1136, 1004, 918, 850, 817, 740, 698 cm . HR-ESI-MS
calcd for C13H9N5O6Na (M＋Na＋) 354.0445, found
Chin. J. Chem. 2010, 28, 1193— 1198
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1195

Yang et al.
FULL PAPER
shorter than an aryl group. Electron-donating groups on
the aromatic ring of 1 facilitated the reaction and took a
shorter time for reaction completion than electron-
withdrawing groups at the same positions (Entries 5 and
9), whereas electron-withdrawing substituents pro-
longed the reaction time somewhat. In general, hydra-
zones 1 were more reactive than ketone arylhydra-
zones,9a particularly for those with an aliphatic R.
Before the whole system was filled with NO gas car-
ried by argon, it was found that the O2 concentration in
the system influenced the composition of product and
the reaction time. No product was formed when air (or
O2) was rigorously excluded from the medium. In con-
trast, when there is more oxygen in the system, a fast
reaction occurred, leading to a complex pattern of
products. Most of the products are highly polar com-
pounds that are difficult to be purified. We found that
the best reaction condition is that the argon-purging
time was controlled to 5—10 min and kept at a pressure
of up to ＋10 mm H2O column over local atmospheric
pressure, and NO gas can be inputted in a flask, thus the
desired products were obtained in the presence of trace
oxygen. These results are similar to the reaction of NO
with alken.22
Figure 1 1H NOE difference spectra of 2b.
All the products were identified by 1H and 13C NMR,
NOE 1D, MS, HRMS, and IR. The presence of NH
－1
groups was confirmed by IR bands near 3200 cm and
1H NMR singlet peaks near δ 11.3. Products 2 were
identified to have (E)-configurations both for alkyl and
aryl aldehyde hydrazones by NOE experiments. The
chemical shift and 1D-NOESY (η%) of Hb are listed in
Table 2. The observation of NOE enhancement of
Figure 2 1H NOE difference spectra of 2e.
α-proton Hb signals of alkyl (R＝alkyl) for 2a— 2d or
ortho-proton Hb signals of aryls (R＝aryl) for 2e— 2j
resulted from irradiation of NH protons (Ha, about δ
11.3) as shown in Figures 1 and 2.
Table 2 1H NOE difference spectral data for 2a— 2j
1
Figures 3 and 4 show H NOE difference spectra of
Ha
δ
Hb
Product
R
1b and 1e, respectively. An NOE enhancement was ob-
served at proton Hb of the C—N double bond upon ir-
radiation of proton Ha of NH in 1. This indicates that
Ha was related to Hb, that is, R (alkyl or aryl) and
NHAr1 groups are on opposite sides of the C—N double
δ
NOESY (η%)
3.80
2a
2b
2c
2d
CH3
11.12
11.29
11.32
11.29
1.67
3.03
2.95
3.50
n-C3H7
i-C4H9
i-C3H7
5.72
6.49
1
bond. Figures 1 and 2 display H NOE difference spec-
4.13
tra of 2b and 2e. NOE enhancements were observed at
Hb upon irradiation of Ha, giving η% Hb of 5.72% for
2e
11.38
7.50
2.78
2f
2g
2h
11.33
11.28
11.73
7.72
7.52
7.58
3.10
2.66
2.46
2j
11.45
6.96, 7.15
4.32
Figure 3 1H NOE difference spectra of 1b.
1196
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Chin. J. Chem. 2010, 28, 1193— 1198

Configuration-Specific Reaction of Nitric Oxide with Aldehyde Arylhydrazones
Figure 6 Molecular structure of 2e and its Newman project
viewed along the N(1)— C(7) bond.
Figure 4 1H NOE difference spectra of 1e.
0.1487(2) nm; C(7)—N(4), 0.1270(2) nm] and has an
(E)-configuration. Figure 6 shows the molecular struc-
ture of 2e and its Newman project viewed along the N(1)
—C(7) bond, in which an NO2 group linked on the car-
bon atom C(7) [i.e., C(1')-atom; N(3)—C(7), 0.1489(4)
nm, C(7) — N(1), 0.1273(4) nm] and has an
(E)-configuration. Both the C(7)—N(4) bond length of
0.1270 nm in 2b and the C(7)—N(1) bond length of
0.1273 nm in 2e confirm that their imine double bonds
are preserved. The benzene ring and alkyl carbon chain
(R＝n-propyl) are nearly coplanarity with a dihedral
angle of 0.9° in 2b, which is much less than that of 6.4°
in 2e between the dinitro-benzene ring and the meth-
oxy-benzene ring. This might be attributed to the steric
effect of R group (R＝p-methoxyphenyl).
2b and of 2.78% for 2e, respectively. They indicate that
R and NHAr1 groups are on the same sides of the C—N
double bond, whereas NO2 and NHAr1 groups are on
opposite sides. This confirms 2 with an (E)-configura-
tion.
Their structures were further confirmed by X-ray
crystallography diffraction. The molecules of both
compounds displayed trans configurations with respect
to the C—N double bonds. Figure 5 shows the molecu-
lar structure of 2b and its Newman project viewed along
the N(4)—C(7) bond, in which an NO2 group is linked
on the carbon atom C(7) [i.e., C(1')-atom; N(5)—C(7),
Based on the reaction of NO and NO2 with al-
kenes,20-23 a mechanism for the reaction of NO with 1 is
proposed in Scheme 1. It is suggested that an initial
electrophilic addition of an NO2 to the carbon of the
imine double bond of 1 leads to formation of radical 3.
It couples with one molecule of NO to give nitroso ad-
duct 4. The addition of two molecules of NO to its ni-
troso group yields N-nitroso-N-nitrite 5. The followed
rearrangement gives the diazonium nitrate 6, which
isomerizes to 7 via an 120° rotation around the C—N
bond. Compound 7 undergoes an anti (180°) elimination
of HNO3 with the expulsion of N2 generating 2. Besides
product 2, nitric acid is also detected in liquid phase.9a
Figure 5 Molecular structure of 2b and its Newman project
viewed along the N(4)— C(7) bond
Scheme 1
Chin. J. Chem. 2010, 28, 1193— 1198
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1197

Yang et al.
FULL PAPER
The existence of components such as N2 and NO2 in the
gas phase was hard to detect due to technical difficul-
ties.
(b) Peng, L. J.; Liu, Z. Q.; Wang, J. T.; Wu, L. M.
Tetrahedron Lett. 2007, 48, 7418.
11 Shen, Y. L.; Liu, Q.; Wu, G. L.; Wu, L. M. Tetrahedron
Lett. 2008, 49, 1220.
12 Liu, Z. Q.; Li, R.; Yang, D. S.; Wu, L. M. Tetrahedron Lett.
2004, 45, 1565.
Conclusion
The present study demonstrats that the reaction of
NO with aldehyde arylhydrazones in the presence of
trace oxygen at room temperature occurs at their C—N
double bonds, uniquely giving C(1')-nitrohydrazones
with (E)-configurations in high yield. It offers an effi-
cient method for preparing C(1')-nitrohydrazones with
(E)-configurations.
13 Liu, Z. Q.; Fan, Y.; Li, R.; Zhou, B.; Wu, L. M.
Tetrahedron Lett. 2005, 46, 1023.
14 Wu, W. T.; Liu, Q.; Shen, Y. L.; Li, R.; Wu, L. M.
Tetrahedron Lett. 2007, 48, 1653.
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Neumann, D. M.; Thangaraj, K.; LeBlane, B. Bioorg. Med.
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Chin. J. Chem. 2010, 28, 1193— 1198