One step from nitro to oxime: a convenient preparation of unsaturated oximes by the reduction of the corresponding vinylnitro compounds

Article abstract of DOI:10.1016/j.tet.2009.10.042

A series of novel unsaturated oximes were conveniently prepared from the corresponding vinylnitro compounds by reduction with SnCl₂·2H₂O. The structures of the oximes were characterized by ¹H and ¹³C NMR, IR and HRMS, and X-ray crystallography analysis of 1-(6-chloro-pyridin-3-ylmethyl)-4,5-dihydro-1H-imidazole-2-carbaldehyde oxime 2a reveals that, the hydroxyl group is arranged in a trans configuration. Some evidences from a brief investigation suggest that these oximes seem to be formed by reduction of the aci form of nitro aliphatic compounds.

Full text of DOI:10.1016/j.tet.2009.10.042

Tetrahedron 65 (2009) 10377–10382
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One step from nitro to oxime: a convenient preparation of unsaturated oximes
by the reduction of the corresponding vinylnitro compounds
,
b
,
a,
*
Kewei Wang a, Xuhong Qian a , Jingnan Cui
*
a State Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 89, Zhongshan Road 158, Dalian 116012, China
b Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, PO Box 544, 130 Meilong Road, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel unsaturated oximes were conveniently prepared from the corresponding vinylnitro
compounds by reduction with SnCl2$2H2O. The structures of the oximes were characterized by 1H and
13C NMR, IR and HRMS, and X-ray crystallography analysis of 1-(6-chloro-pyridin-3-ylmethyl)-4,5-di-
hydro-1H-imidazole-2-carbaldehyde oxime 2a reveals that, the hydroxyl group is arranged in a trans
configuration. Some evidences from a brief investigation suggest that these oximes seem to be formed by
reduction of the aci form of nitro aliphatic compounds.
Received 14 September 2009
Accepted 13 October 2009
Available online 15 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
sparse and their preparation is of great difficulty.27 Herein we wish
to report the results regarding the preparation of unsaturated
Oximes are of great interest as intermediates in organic syn-
thesis,1–6 for example, oxime ether, as one of the important oxime
derivatives, has long been recognized in the fields of agro-
chemistry7–11 and medicinal chemistry.12–14 Furthermore for their
own biological activities, oximes are particularly significant as an-
timicrobial agents,15 insecticides,16 vasodilators,17 inhibitors of
P450 17,18 and antioxidants.19
Oximes are commonly prepared by three methods. The first is
the most known method by the condensation of carbonyl com-
pounds with hydroxylamine, however sometimes this method is
not applicable for the preparation of unsaturated oximes.20 The
second is the often used method by N-oxides reaction with al-
kene,21–23 and the third method is a practical one by treatment of
precursors nitroalkanes with alkali.24 In addition, there are a few
reports that oximes can be obtained directly from nitro benzylic
compounds by electrochemical reduction but no selectivity with
simultaneous formation of hydroxylamine,25 or by homogeneous
catalyzed reduction of saturated nitro aliphatic compounds with
the cuprous CO complexes as the catalyst but under rigorous re-
action conditions.26
oxime from vinylnitro compounds by reduction with tin(II) chloride
dihydrate (SnCl2$2H2O).
2. Results and discussion
Compound 1a was chosen as a model substrate in order to test
the effectiveness of the reaction. In a typical experiment, placing 1a
and an excess of SnCl2$2H2O in dichloromethane resulted in the
formation of the unsaturated oxime 2a with complete consumption
of the substrate in 5 h at room temperature (Scheme 1). In opti-
mization of the reaction, it was found that other solvents, such as
acetonitrile, ethyl acetate, methanol, and ethanol, were not suitable
because of their poor solubility to the substrate. The optimal
R2
R2
SnCl2* 2H2O
CH2Cl2, r.t.
X
X
R1
R1
N
N
NO2
N
OH
1
2
Recently in research of insecticide, we unexpectedly found that,
reduction of cyclic vinylnitro compound CH-IMI(1a), a famous po-
tential neonicotinoid pesticide, gave an unsaturated oxime, but not
the corresponding hydroxylamine and/or amino compounds. The
literature describing such structures, unsaturated oximes, is rather
N
S
R1
=
=
Cl
,
,
,
,
,
N
N
N
Cl
,
S
O
R2
CH2
,
CH2
2
3
,
,
* Corresponding authors. Tel.: þ86 411 39893872; fax: þ86 411 83673488.
E-mail addresses: xhqian@ecust.edu.cn (X. Qian), jncui@dlut.edu.cn (J. Cui).
Scheme 1. Synthesis of unsaturated cyclic oximes 2a–s from vinylnitro compounds
1a–s.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.042

10378
K. Wang et al. / Tetrahedron 65 (2009) 10377–10382
the method described previously,28 were reduced under the opti-
mal conditions and the results summarized in Table 1. In each case
the corresponding oximes were obtained. Although the conversion
of vinylnitro compounds to the corresponding oximes was com-
plete within 5 h according to the TLC analysis, the yields of the
isolated products were moderate, due to the so good solubility of
the oximes in water that it is difficult to be extracted with
dichloromethane in the work-up procedure.
Table 1
Reduction of nitro compounds 1 to the corresponding oximes 2a
Substrate
R1
R2
Product
Yield (%)
45
1a
–(CH2)2–
2a
Cl
Cl
N
N
S
1b
1c
1d
1e
1f
–(CH2)2–
–(CH2)2–
–(CH2)2–
–(CH2)2–
–(CH2)2–
–(CH2)2–
–(CH2)3–
–(CH2)3–
–(CH2)3–
–(CH2)3–
–(CH2)3–
2b
2c
2d
2e
2f
43
40
40
62
58
60
48
40
65
61
64
68
65
60
58
75
72
The structures of the unsaturated oximes 2 were character-
ized by IR, 1H, and 13C NMR, HRMS, and X-ray crystallography.
The IR spectra of compounds showed C]N, N–O and O–H
stretchinꢀg1 bands at 1630–1640 cmꢀ1, 920–940 cmꢀ1 and 3420–
N
N
3440 cm
, respectively, and O–H deformation vibration at
1300 cmꢀ1. The 1H NMR of spectra of unsaturated oximes 2
showed a singlet at 7.70–7.79 ppm, which attributed to CH in the
–CH]NOH, compared to the singlet at 6.60–6.66 ppm, which
attributed to CH in the ]CH–NO2. Further, the structure of 2a
was determined by X-ray single-crystal diffraction analysis
(Fig. 1) showing a non-planar framework and the hydroxyl group
arranged in a trans configuration.
O
S
1g
1h
1i
2g
2h
2i
Cl
Cl
N
N
S
1j
2j
1k
1l
2k
2l
O
S
1m
1n
1o
1p
1q
1r
2m
2n
2o
2p
2q
2r
Cl
Cl
N
N
S
N
Figure 1. X-ray single-crystal structure of 2a.
N
Motherwell et al. have ever reported that the oximes can be
obtained by in situ tautomerization of the diazene dioxides dimers
of the corresponding nitroso compounds (Scheme 2).29 However
Zuman and Shah think that the dimers are never formed in the
reduction of nitro compounds,30 due to the significant kinetic in-
hibition to the dimers formation or a higher rate of further re-
duction under the experiment conditions.31 It is presumed that the
unsaturated oximes 2 could not be formed through tautomeriza-
tion of the corresponding dimers.
O
S
1s
2s
72
a
Optimal conditions: the amount of SnCl2$2H2O was 5.5 equiv of the substrate
and dichloromethane as solvent.
amount of the reducing agent required for a satisfactory yield was
proved to be 5.5 equiv with respect to the substrate.
In order to explore the scope of the reaction, a series of cyclic
vinylnitro compounds 1b–s (Scheme 1), which were synthesized by
Reduction of nitro group to amino group under acidic conditions
is usually as follows (Scheme 3): the nitro group is first reduced via
two electrons to form the nitroso group, which accepts another two
electrons to form hydroxylamine group and then converted to
R1
R1
-
O
+
O
RS
N
Tautomerisation
+
RS
N
N
S
N
OH
+
R
N
O
R1
-
RS
O
R1
or hv
R1
SR
diazene dioxides dimers
nitroso
oximes
Scheme 2. Tautomerization of the diazene dioxide dimers to the corresponding oximes.

K. Wang et al. / Tetrahedron 65 (2009) 10377–10382
10379
O
O
reduction conditions. This indicated that NH in the cyclic and
acyclic vinylnitro compounds 1 could make them form more stable
aci-1, while O, S, and N of tertiary amine in 3, 4, and 5 could not lead
to form stable aci form. The results imply that path b is more
reasonable.
2e-
2e-
2e-
O
H
H
HO
H
N
R
N
R
N
R
N
R
Scheme 3. The general principle of nitro reduction to amino group.
3. Conclusion
amino group.32 Nitroso compound is a highly reactive intermediate
in the reduction conditions, which cannot be isolated and it can be
reduced to the corresponding hydroxylamine, or amine further by
control of the reduction conditions. Generally there is an equilib-
rium between nitro form and aci form in nitroalkanes, and the aci is
less stable than the nitro.33 In our case, the aci could be more stable
because of formation of the strong conjugative interaction between
the two C]N bonds. On the basis of the known reductive mecha-
nism of nitro group and the above studies, two possible mecha-
nisms path a and path b are proposed in the formation of oximes 2
(Scheme 4). In path a, the nitro-1 is reduced via two electrons to
form the nitroso, which is an unstable intermediate, the fast nitroso
to cis-2 prototropy may prevent the reduction of NO to NHOH, and
then cis-2 tautomerize to more stable trans-2.34 In path b, the nitro-
1 could exist in aci-1 and the aci-1 is reduced via two electrons to
form cis-2, which then tautomerize to trans-2.
We have successfully synthesized a series of unsaturated oximes
by reduction of the corresponding substituted vinylnitro com-
pound using SnCl2$2H2O under mild conditions. The procedure is
remarkably simple, and unique chem-selective without catalyst in
preparing such oximes, which are usually difficult to be prepared
by traditional methods. This is another example of direct conver-
sion of nitro compounds to oximes and the research extends the
application scope of nitro reduction.
4. Experimental
4.1. General
Melting points were obtained with an X-6 micro-melting
point apparatus and are uncorrected. The infrared (IR) spectra
R2
N
N
R1
N
H
O
2e-
R2
a
R2
h
t
R2
a
nitroso
p
N
N
R1
N
N
R1
N
N
R1
N
H
O
OH
N
OH
2e-
N
O
R2
N
nitro-1
p
a
cis-2
trans-2
t
h
R1
b
N
OH
N
O
aci-1
Scheme 4. Proposed mechanism for formation of oximes 2.
In order to confirm which path more reasonable, a brief in-
vestigation into the scope of this reduction was performed. In
controlled experiments, attempts to reduce the vinylnitro com-
pounds 3, 4 and 5 (Fig. 2) gave neither the corresponding oximes
nor the corresponding hydroxylamine or amine with no conversion
of the vinylnitro compound, while reducing acyclic vinylnitro
compound 1t (Fig. 2), a commercialized insecticide called niten-
pyram, gave the corresponding oximes 2t under the same
were recorded on a Nicolet 20DXB FR-IR spectrometer using
potassium bromide pellets or films. The 1H and 13C NMR spectra
were obtained on a Varian INOVA 400 MHz NMR spectrometer
with DMSO-d6 as the solvent and TMS as the internal standard.
High-resolution mass spectra (HRMS) were obtained on HPLC-Q-
Tof MS (Mcrio) spectrometer. X-ray single-crystal diffraction
experiments were carried out on a Bruker Smart APEXII diffrac-
tometer. Flash chromatography was performed on silica gel. All
the solvents were analytic grade. All chemicals or reagents and
nitenpyram (1t) were purchased from standard commercial
suppliers.
NO2
O
N
N
H
N
NO2
N
Cl
4.2. General procedure for substituted 2-nitromethylidene
substrates 1a–e, 1h–j, and 1m–q
1t
3
Compounds 1a–e, 1h–j, and 1m–q were prepared according to
the reported literature.28 2-Chloro-5-(chloromethyl) pyridine
(1.62 g, 10 mmol) in acetonitrile (30 ml) was added dropwise to
ethylenediamine (2.40 g, 40 mmol) in acetonitrile (20 ml) while
stirring in an ice bath. After removing from the ice bath and stir-
ring overnight at room temperature, the solvent was evaporated.
Aqueous sodium hydroxide (1 M, 50 ml) was added to the residue,
S
N
N
O2N
S
NO2
4
5
Figure 2. Structure of 1t, 3, 4 and 5.

10380
K. Wang et al. / Tetrahedron 65 (2009) 10377–10382
which was then extracted with dichloromethane. The organic
layer was dried over anhydrous magnesium sulfate and evapo-
rated to afford N-(2-chloro-pyridinylmethyl)ethylenediamine
(1.39 g, 75% yield). N-(2-Chloro-pyridinylmethyl) ethylenedi-
amine (0.93 g, 5 mmol) in ethanol (20 ml) was added dropwise to
1,1-bis(methylthio)-2-nitroethylene (0.83 g, 5 mmol) in ethanol
(10 ml). The mixture was refluxed for 4 h. After evaporating the
solvent, the residue was recrystallized from ethanol to afford 1-N-
(2-chloro-pyridinylmethyl)-2-nitromethylene-imidazolidine 1a
(0.95 g, 75% yield). Compounds 1b–e, 1h–j, and 1m–q were sim-
ilarly prepared.
DMSO-d6)
d
(ppm) 11.68 (br, 1H), 8.51 (d, 1H, J¼4.4 Hz), 7.78 (t, 1H,
J¼8.0 Hz), 7.72 (s, 1H), 7.28 (t, 2H, J¼7.2 Hz), 4.80 (s, 2H), 3.71 (t, 2H,
J¼10.0 Hz), 3.35 (t, 2H, J¼10.0 Hz); 13C NMR (100 MHz, DMSO-d6)
d
(ppm) 158.8, 157.9, 149.1, 142.1, 136.7, 122.1, 121.3, 52.6, 52.0, 50.7;
HRMS (ESI) calculated for C10H13N4O [MþHþ] 205.1089, found
205.1080.
4.4.4. 1-Pyridin-3-ylmethyl-4,5-dihydro-1H-imidazole-2-carbalde-
hyde oxime (2d). Yield 40%; gray powders; mp 144.4–145.6 ꢁC; IR
(KBr, cmꢀ1): 3430, 1637, 1556, 1276, 925; 1H NMR (400 MHz,
DMSO-d6)
d (ppm) 11.74 (br, 1H), 8.49 (s, 2H), 7.73 (s, 1H), 7.67 (d,
1H, J¼7.6 Hz), 7.38 (t, 1H, J¼7.6 Hz), 4.71 (s, 2H), 3.68 (t, 2H,
4.3. General procedure for substituted 2-nitromethylidene
substrates 1f–g, 1k–l, and 1r–s
J¼6.0 Hz), 3.26 (t, 2H, J¼6.0 Hz); 13C NMR (100 MHz, DMSO-d6)
d
(ppm) 158.5, 148.8, 148.3, 142.1, 135.1, 133.8, 123.5, 52.6, 50.5,
48.3; HRMS (ESI) calculated for C10H13N4O [MþHþ] 205.1089,
Compounds 1f–g, 1k–l, and 1r–s were prepared according to the
report.35 A solution of ethylenediamine (2.4 g, 40 mmol) in methanol
(20 ml) was stirred at 0 ꢁC during the dropwise addition of 2-fur-
aldehyde (0.96 g, 10 mmol). After the addition was completed, the
solution was stirred and maintained at 0 ꢁC while NaBH4 (0.57 g,
15 mmol) was added cautiously in small portions. The reaction mix-
ture was allowed to warm to ambient temperature and stirred for 2 h.
The resulting cloudy solution was filtered, the filtrate was concen-
trated and the residual oil was partitioned between dichloromethane
and H2O. The dichloromethane layer was dried over magnesium
sulfate and evaporated to afford N-(2-furalmethyl) ethylenediamine
(1.02 g, 70% yield) and then N-(2-furalmethyl)ethylenediamine reac-
ted with 1,1-bis(methylthio)-2-nitroethylene to afford 1f in 70% yield.
Compounds 1g, 1k–l, and 1r–s were similarly prepared.
found 205.1084.
4.4.5. 1-Benzyl-4,5-dihydro-1H-imidazole-2-carbaldehyde
(2e). Yield 62%; gray powders; mp 141.8–143.6 ꢁC; IR (KBr, cmꢀ1):
3435, 1633, 1555, 1281, 928; 1H NMR (400 MHz, DMSO-d6)
(ppm)
oxime
d
11.85 (br, 1H), 7.74 (s, 1H), 7.34 (t, 2H, J¼8.0 Hz), 7.26 (t, 3H,
J¼8.0 Hz), 4.70 (s, 2H), 3.67 (t, 2H, J¼10.0 Hz), 3.24 (t, 2H,
J¼10.0 Hz); 13C NMR (100 MHz, DMSO-d6)
d (ppm) 158.6, 141.9,
138.1, 128.4, 127.3, 127.0, 52.3, 50.4, 50.3; HRMS (ESI) calculated for
C11H14N3O [MþHþ] 204.1137, found 204.1147.
4.4.6. 1-Furan-2-ylmethyl-4,5-dihydro-1H-imidazole-2-carbalde-
hyde oxime (2f). Yield 58%; white powders; mp 132.5–133.3 ꢁC; IR
(KBr, cmꢀ1): 3420, 1636, 1582, 1291, 958; 1H NMR (400 MHz,
DMSO-d6)
d (ppm) 11.90 (br, 1H), 7.70 (s, 1H), 7.59 (s, 1H), 6.40 (d,
4.4. General procedure for preparation of unsaturated
oximes 2a–t
1H), 6.26 (s, 1H), 4.68 (s, 2H), 3.64 (t, 2H, J¼5.6 Hz), 3.28 (t, 2H,
J¼5.6 Hz); 13C NMR (100 MHz, DMSO-d6)
d (ppm) 158.5, 147.8,
143.8, 135.1, 110.7, 110.0, 49.7, 43.1, 42.4; HRMS (ESI) calculated for
A solution of 1a (1.53 g, 6 mmol) in dichloromethane (100 ml)
was treated with solid SnCl2$2H2O (7.4 g, 33 mmol). The mixture
was stirred at ambient temperature under nitrogen for 5 h and then
poured cautiously into saturated aqueous NaHCO3. The resulting
gelatinous emulsion was filtered through a pad of diatomite, and
the biphasic filtrate was extracted with dichloromathane five times.
The combined organic extracts were dried over anhydrous mag-
nesium sulfate and concentrated in vacuo, affording the oxime 2a
(0.64 g, 45% yield) that was purified by silica gel chromatography
(CH2Cl2/CH3OH¼4:1, v/v).
C9H12N3O2 [MþHþ] 194.0930, found 194.0935.
4.4.7. 1-Thiophen-2-ylmethyl-4,5-dihydro-1H-imidazole-2-carbalde-
hyde oxime (2g). Yield 60%; white powders; mp 136.2–137.7 ꢁC;
IR (KBr, cmꢀ1): 3427, 1630, 1598, 1290, 927; 1H NMR (400 MHz,
DMSO-d6)
d
(ppm) 11.88 (br, 1H), 7.75 (s, 1H), 7.44 (dd, 1H, J¼4.0,
2.0 Hz), 7.00 (t, 2H, J¼4.0 Hz), 4.88 (s, 2H), 3.65 (t, 2H, J¼6.0 Hz),
3.26 (t, 2H, J¼6.0 Hz); 13C NMR (100 MHz, DMSO-d6)
d
(ppm) 158.3, 142.1, 140.5, 126.7, 126.3, 125.5, 52.6, 49.9, 45.3;
HRMS (ESI) calculated for C9H12N3O [MþHþ] 210.0701, found
210.0691.
4.4.1. 1-(6-Chloro-pyridin-3-ylmethyl)-4,5-dihydro-1H-imidazole-2-
carbaldehyde oxime (2a). Yield 45%; white powders; mp 142.5–
143.8 ꢁC; IR (KBr, cmꢀ1): 3434, 1632, 1566, 1296, 929; 1H NMR
4.4.8. 1-(6-Chloro-pyridin-3-ylmethyl)-1,4,5,6-tetrahydro-pyrimi-
dine-2-carbaldehyde oxime (2h). Yield 48%; white powders; mp
153.1–154.3 ꢁC; IR (KBr, cmꢀ1): 3447,1630,1586,1299, 937; 1H NMR
(400 MHz, DMSO-d6) d (ppm) 11.54 (br, 1H), 7.73 (s, 1H), 7.60 (s, 1H),
4.84 (s, 2H), 3.67 (t, 2H, J¼9.6 Hz), 3.33 (t, 2H, J¼9.6 Hz); 13C NMR
(400 MHz, DMSO-d6)
d (ppm) 11.46 (br,1H), 7.60 (s, 1H), 7.39 (s, 1H),
(100 MHz, DMSO-d6) d (ppm) 158.3, 149.0, 148.9, 142.1, 138.9, 124.1,
4.73 (s, 2H), 3.31–3.15 (m, 4H), 1.68 (m, 2H); 13C NMR (100 MHz,
52.7, 50.6, 47.6; HRMS (ESI) calculated for C10H12N4OCl [MþHþ]
DMSO-d6) d (ppm) 158.3, 149.0, 148.8, 138.7, 133.6, 124.1, 50.9, 46.0,
239.0700, found 239.0692.
43.5, 20.8; HRMS (ESI) calculated for C11H14N4OCl [MþHþ]
253.0856, found 253.0846.
4.4.2. 1-(2-Chloro-thiazol-5-ylmethyl)-4,5-dihydro-1H-imidazole-2-
carbaldehyde oxime (2b). Yield 43%; white powders; mp 138.5–
139.7 ꢁC; IR (KBr, cmꢀ1): 3435, 1632, 1563, 1281, 922; 1H NMR
4.4.9. 1-(2-Chloro-thiazol-5-ylmethyl)-1,4,5,6-tetrahydro-pyrimi-
dine-2-carbaldehyde oxime (2i). Yield 40%; white powders; mp
138.5–139.4 ꢁC; IR (KBr, cmꢀ1): 3430,1617,1564,1320, 939; 1H NMR
(400 MHz, DMSO-d6)
d
(ppm) 11.76 (br, 1H), 8.33 (d, 1H, J¼2.0 Hz),
7.77 (s, 1H), 7.75 (d, 1H, J¼2.0 Hz), 7.51 (d, 1H, J¼8.0 Hz), 4.71 (s, 2H),
(400 MHz, DMSO-d6) d (ppm) 11.26 (br, 1H), 8.30 (s, 1H), 7.73 (d, 1H,
3.70 (t, 2H, J¼10.0 Hz), 3.31 (t, 2H, J¼10.0 Hz); 13C NMR (100 MHz
J¼8.0 Hz), 7.51 (d, 1H, J¼8.0 Hz), 7.44 (s, 1H), 4.66 (s, 2H), 3.32 (t, 2H,
DMSO-d6)
d (ppm) 157.7, 150.0, 142.2, 140.0, 138.4, 52.7, 50.1, 43.3;
J¼5.6 Hz), 3.12 (t, 2H, J¼5.6 Hz), 1.72 (t, 2H, J¼5.6 Hz); 13C NMR
HRMS (ESI) calculated for C8H10N4OSCl [MþHþ] 245.0264, found
(100 MHz, DMSO-d6) d (ppm) 150.5, 150.1, 146.8, 140.1, 139.1, 47.2,
245.0260.
45.5, 44.0, 20.9; HRMS (ESI) calculated for C9H12N4OSCl [MþHþ]
259.0420, found 259.0415.
4.4.3. 1-Pyridin-2-ylmethyl-4,5-dihydro-1H-imidazole-2-carbalde-
hyde oxime (2c). Yield 40%; gray powders; mp 125.6–127.1 ꢁC; IR
(KBr, cmꢀ1): 3416, 1636, 1556, 1295, 930; 1H NMR (400 MHz,
4.4.10. 1-Benzyl-1,4,5,6-tetrahydro-pyrimidine-2-carbaldehyde
oxime (2j). Yield 65%; white powders; mp 125.8–127.1 ꢁC; IR (KBr,

K. Wang et al. / Tetrahedron 65 (2009) 10377–10382
10381
cmꢀ1): 3390, 1650, 1568, 1321, 933; 1H NMR (400 MHz, DMSO-d6)
(ppm) 11.58 (br, 1H), 8.33 (s, 1H), 741–7.29 (m, 5H), 4.87 (s, 2H),
3.49–3.35 (m, 4H), 1.69 (m, 2H); 13C NMR (100 MHz, DMSO-d6)
J¼7.6 Hz), 4.91 (d, 1H, J¼16.0 Hz), 4.51 (d, 1H, J¼16.0 Hz), 2.94 (t,
1H, J¼12.0 Hz), 2.62 (t, 1H, ,J¼12.0 Hz), 2.14–1.65 (m, 4H), 1.30–
d
1.22 (m, 4H); 13C NMR (100 MHz, DMSO-d6)
d (ppm) 160.1, 148.8,
d
(ppm) 151.9, 144.4, 138.0, 128.5, 127.0, 126.8, 53.8, 46.0, 42.8, 20.7;
148.2, 142.7, 135.2, 134.0, 123.4, 70.5, 70.3, 47.2, 30.4, 28.9, 24.9,
23.8; HRMS (ESI) calculated for C14H19N4O [MþHþ] 259.1559,
found 259.1548.
HRMS (ESI) calculated for C12H16N3O [MþHþ] 218.1293, found
218.1287.
4.4.11. 1-Furan-2-ylmethyl-1,4,5,6-tetrahydro-pyrimidine-2-carbal-
dehyde oxime (2k). Yield 61%; white powders; mp 151.8–153.4 ꢁC;
IR (KBr, cmꢀ1): 3433, 1649, 1571, 1297, 928; 1H NMR (400 MHz,
4.4.17. 1-Benzyl-4,5,6,7,8,9-hexahydro-1H-benzoimidazole-2-carbal-
dehyde oxime (2q). Yield 75%; white powders; mp 148.3–149.9 ꢁC;
IR (KBr, cmꢀ1): 3434, 1631, 1561, 1303, 922; 1H NMR (400 MHz,
DMSO-d6)
d
(ppm) 11.12 (br, 1H), 8.43 (s, 1H), 7.70 (s, 1H), 6.52 (d,
DMSO-d6)
d
(ppm) 11.41 (br, 1H), 7.73 (s, 1H), 7.31 (d, 2H, J¼6.8 Hz),
1H, J¼3.2 Hz), 6.45 (d, 1H, J¼3.2 Hz), 4.89 (s, 2H), 3.53 (t, 2H,
7.24 (t, 3H, J¼6.8 Hz), 4.77 (d,1H, J¼16.0 Hz), 4.63 (d,1H, J¼16.0 Hz),
2.93 (t, 1H, J¼11.2 Hz), 2.57 (t, 1H, J¼11.2 Hz), 2.15–1.85 (m, 2H),
1.70–1.63 (m, 2H),1.30–1.22 (m, 4H); 13C NMR (100 MHz, DMSO-d6)
J¼5.6 Hz), 3.34 (t, 2H, J¼5.6 Hz), 1.91 (t, 2H, J¼5.6 Hz); 13C NMR
(100 MHz DMSO-d6)
d (ppm) 153.9, 148.5, 144.4, 138.9, 111.2, 110.4,
48.1, 47.0, 38.3, 18.7; HRMS (ESI) calculated for C10H14N3O2 [MþHþ]
d (ppm) 160.2, 142.6, 138.1, 128.2, 127.4, 126.9, 70.4, 69.7, 49.3, 30.4,
208.1086, found 208.1093.
28.8, 24.9, 23.8; HRMS (ESI) calculated for C15H20N3O [MþHþ]
258.1606, found 258.1597.
4.4.12. 1-Thiophen-2-ylmethyl-1,4,5,6-tetrahydro-pyrimidine-2-car-
baldehyde oxime (2l). Yield 64%; white powders; mp 154.2–
156.0 ꢁC; IR (KBr, cmꢀ1): 3426, 1646, 1566, 1315, 932; 1H NMR
4.4.18. 1-Furan-2-ylmethyl-4,5,6,7,8,9-hexahydro-1H-benzoimida-
zole-2-carbaldehyde oxime (2r). Yield 72%; white powders; mp
136.6–138.1 ꢁC; IR (KBr, cmꢀ1): 3433,1631,1542,1299, 928; 1H NMR
(400 MHz, DMSO-d6)
1H), 7.17 (s, 1H), 7.05 (s, 1H), 5.06 (s, 2H), 3.53–3.36 (m, 4H), 1.93 (m,
2H); 13C NMR (100 MHz, DMSO-d6)
(ppm) 159.3, 156.2, 136.1,
d (ppm) 10.48 (br, 1H), 8.42 (s, 1H), 7.58 (s,
(400 MHz, DMSO-d6) d (ppm) 11.89 (br, 1H), 7.73 (s,1H), 7.58 (s, 1H),
d
6.38 (t, 1H, J¼3.2 Hz), 6.26 (d, 1H, J¼3.2 Hz), 4.97 (d, 1H, J¼16.4 Hz),
4.40 (d, 1H, J¼16.4 Hz), 2.93–2.86 (m, 1H), 2.49–2.44 (m, 1H), 2.14
(d, 1H, J¼8.8 Hz), 2.06 (d, 1H, J¼8.8 Hz), 1.72 (d, 2H, J¼12.0 Hz),
129.5, 128.1, 127.7, 50.4, 44.3, 38.0, 18.3; HRMS (ESI) calculated for
C10H14N3OS [MþHþ] 224.0858, found 224.0853.
1.34–1.23 (m, 4H); 13C NMR (100 MHz DMSO-d6)
d (ppm) 160.8,
4.4.13. 1-(6-Chloro-pyridin-3-ylmethyl)-4,5,6,7,8,9-hexahydro-1H-
benzoimidazole-2-carbaldehyde oxime (2m). Yield 68%; white
powders; mp 162.0–162.9 ꢁC; IR (KBr, cmꢀ1): 3435, 1631, 1569,
151.5, 143.1, 142.7, 110.8, 108.9, 70.4, 69.3, 42.1, 30.8, 28.6, 25.4, 24.3;
HRMS (ESI) calculated for C13H18N3O2 [MþHþ] 248.1399, found
248.1392.
1300, 920; 1H NMR (400 MHz, DMSO-d6)
d (ppm) 12.04 (br, 1H),
7.70 (s, 1H), 7.60 (s, 1H), 4.89 (d, 1H, J¼16.0 Hz), 4.74 (d, 1H,
J¼16.0 Hz), 2.89 (t,1H, J¼6.4 Hz), 2.56 (t, 1H, J¼6.4 Hz), 2.13 (m, 2H),
1.71 (m, 2H), 1.28–1.21 (m, 4H); 13C NMR (100 MHz, DMSO-d6)
4.4.19. 1-Thiophen-2-ylmethyl-4,5,6,7,8,9-hexahydro-1H-benzoimi-
dazole-2-carbaldehyde oxime (2s). Yield 72%; white powders; mp
146.4–147.1 ꢁC; IR (KBr, cmꢀ1): 3434, 1632, 1565, 1300, 918; 1H
d
(ppm) 158.0, 148.9, 148.8, 142.7, 138.8, 134.0, 124.0, 61.9, 60.7, 44.7,
NMR (400 MHz, DMSO-d6) d (ppm) 11.98 (br, 1H), 7.74 (s, 1H),
28.3, 23.3, 20.8, 19.7; HRMS (ESI) calculated for C14H18N4OCl
7.42 (dd, 1H, J¼4.0, 2.4 Hz), 6.98 (t, 2H, J¼4.0 Hz), 5.14 (d, 1H,
J¼16.0 Hz), 4.65 (d, 1H J¼16.0 Hz), 2.92 (t, 1H J¼14.4 Hz), 2.55 (t,
1H, J¼14.4 Hz), 2.15–2.06 (m, 2H), 1.72 (d, 2H, J¼10.2 Hz), 1.36–
[MþHþ] 293.1169, found 293.1183.
4.4.14. 1-(2-Chloro-thiazol-5-ylmethyl)-4,5,6,7,8,9-hexahydro-1H-
benzoimidazole-2-carbaldehyde oxime (2n). Yield 65%; white
powders; mp 163.8–164.4 ꢁC; IR (KBr, cmꢀ1): 3434, 1631, 1560,
1.22 (m, 4H); 13C NMR (100 MHz, DMSO-d6)
d (ppm) 160.3, 143.1,
139.9, 127.3, 127.2, 126.3, 70.5, 68.7, 44.0, 30.8, 28.7, 25.4, 24.3;
HRMS (ESI) calculated for C13H18N3OS [MþHþ] 264.1171, found
264.1179.
1292, 922; 1H NMR (400 MHz, DMSO-d6)
d (ppm) 11.84 (br, 1H),
8.33 (s, 1H), 7.75 (dd, 1H, J¼8.0, 2.0 Hz), 7.70 (s, 1H), 7.50 (d, 1H,
J¼8.0 Hz), 4.81 (d, 1H, J¼16.4 Hz), 4.60 (d, 1H, J¼16.4 Hz), 3.75 (t,
1H, J¼6.4 Hz), 3.35 (t, 1H, J¼6.4 Hz), 1.72–1.41 (m, 4H), 1.71 (m,
4.4.20. N-(6-Chloro-pyridin-3-ylmethyl)-N-ethyl-N0-methyl-acet-
amidine-2-carbaldehyde oxime (2t). Yield 65%; white powders; mp
146.8–147.8 ꢁC; IR (KBr, cmꢀ1): 3434, 1638, 1570, 1291, 916; 1H NMR
2H), 1.21–1.16 (m, 4H); 13C NMR (100 MHz DMSO-d6)
d (ppm)
159.7, 150.6, 143.3, 140.9, 138.3, 70.8, 69.6, 42.5, 30.7, 28.7, 25.4,
24.2; HRMS (ESI) calculated for C12H16N4OSCl [MþHþ] 299.0733,
found 299.0742.
(400 MHz, DMSO-d6)
d
(ppm) 11.63 (br, 1H), 8.30 (d, 1H, J¼2.4 Hz),
7.90 (s, 1H), 7.72 (d, 1H, J¼8.0 Hz) 7.45 (d, 2H, J¼8.0 Hz), 4.49 (s, 2H),
3.20 (m, 2H), 2.93 (s, 3H), 0.98 (t, 3H, J¼7.2 Hz); 13C NMR (100 MHz,
DMSO-d6)
d (ppm) 153.4, 148.9, 148.5, 142.4, 138.9, 134.6, 123.8,
4.4.15. 1-Pyridin-2-ylmethyl-4,5,6,7,8,9-hexahydro-1H-benzoimida-
zole-2-carbaldehyde oxime (2o). Yield 60%; white powders; mp
149.3–150.2 ꢁC; IR (KBr, cmꢀ1): 3427, 1673, 1570, 1302, 928; 1H
46.1, 42.3, 36.4, 13.3; HRMS (ESI) calculated for C11H16N4OCl
[MþHþ] 255.1013, found 255.1008.
NMR (400 MHz, DMSO-d6)
d
(ppm) 11.69 (br, 1H), 8.48 (d, 1H,
4.4.21. X-ray data. C10H11Cl1N4O1 2a, unit cell parameters:
J¼4.0 Hz), 7.76 (t, 1H, J¼7.6 Hz), 7.71 (s, 1H), 7.35 (t, 1H, J¼7.6 Hz),
7.25 (d, 1H, J¼5.6 Hz), 4.82 (d, 1H, J¼16.4 Hz), 4.71 (d, 1H,
J¼16.4 Hz), 2.94 (t, 1H, J¼14.0 Hz), 2.65 (t, 1H, J¼6.4 Hz), 2.14–1.63
a¼11.3228(17),
¼97.268(2), ¼90.00, space group P21/c.
The crystallographic data for the structure 2a reported in this
paper have been deposited with the Cambridge Crystallographic
Data Center as supplementary publication no. CCDC 734794 for
compounds 2a. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB21EZ, UK [fax:
þ44 1223 336033; email: deposit@ccdc.cam.ac.uk].
b¼9.0996(14),
c¼10.9721(17),
a
¼90.00,
b
g
(m, 4H), 1.31–1.20 (m, 4H); 13C NMR (100 MHz, DMSO-d6)
d
(ppm)
161.0, 157.6, 149.6, 142.9, 137.3, 122.9, 121.8, 70.7, 70.2, 51.2, 29.8,
28.1, 24.3, 23.4; HRMS (ESI) calculated for C14H19N4O [MþHþ]
259.1559, found 259.1558.
4.4.16. 1-Pyridin-3-ylmethyl-4,5,6,7,8,9-hexahydro-1H-benzoimida-
zole-2-carbaldehyde oxime (2p). Yield 58%; white powders; mp
143.3–143.9 ꢁC; IR (KBr, cmꢀ1): 3423, 1674, 1575, 1301, 931; 1H
Acknowledgements
NMR (400 MHz, DMSO-d6)
(d, 1H, J¼4.0 Hz), 7.74 (s, 1H), 7.68 (d, 1H, J¼7.6 Hz), 7.37 (t, 1H,
d
(ppm) 11.76 (br, 1H), 8.51 (s, 1H), 8.46
We are grateful to the National Natural Science Foundation of
China (20536010, 90713030).

10382
K. Wang et al. / Tetrahedron 65 (2009) 10377–10382
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