An in-depth analysis of the effect of substituents on imines in cycloaddition reactions with nitrosoalkenes

Article abstract of DOI:10.1016/j.tet.2006.03.047

An in-depth experimental and theoretical analysis of the reactions of simple acyclic imines with nitrosoalkenes is reported. The effect of the substituents on nitrogen as well as carbon atom of imines on the cycloaddition pathways followed is systematically explored. The reactions of various functionalized imines with nitrosoalkenes leading to the formation of imidazoles and imidazole-N-oxides have also been explored. The plausible mechanisms leading to various heterocycles have been proposed.

Full text of DOI:10.1016/j.tet.2006.03.047

Tetrahedron 62 (2006) 5474–5486
An in-depth analysis of the effect of substituents on imines in
cycloaddition reactions with nitrosoalkenes
*
Alka Marwaha, Parvesh Singh and Mohinder P. Mahajan
Department of Applied Chemistry, Guru Nanak Dev University, Amritsar, Punjab 143005, India
Received 16 November 2005; revised 23 February 2006; accepted 16 March 2006
Available online 27 April 2006
Abstract—An in-depth experimental and theoretical analysis of the reactions of simple acyclic imines with nitrosoalkenes is reported. The
effect of the substituents on nitrogen as well as carbon atom of imines on the cycloaddition pathways followed is systematically explored. The
reactions of various functionalized imines with nitrosoalkenes leading to the formation of imidazoles and imidazole-N-oxides have also been
explored. The plausible mechanisms leading to various heterocycles have been proposed.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
of products in these reactions. However, in recent reports
by Tahdi et al.,7 the effect of substituents present on a-carbon
atom of nitrosoalkenes on the cycloaddition pathways fol-
lowed is not generalized.7 In view of these contradictions
and in order to have a deeper insight regarding the key fac-
tors influencing the [3+2] versus [4+2] cycloaddition reac-
tions, we examined the reactions of various imines with
a-substituted nitrosoalkenes.
The C-nitroso group of arylnitroso, a-chloronitroso, cyano–
nitroso, C-nitroso sugar derivatives, and acylnitroso com-
pounds is known to effectively participate as a 2p component
in hetero Diels–Alder reactions.1 Of these, the acylnitroso
species has been exploited much more extensively than the
other dienophiles.2 On the other hand, a-nitrosostyrenes
have been known to participate as 4p components in Diels–
Alder reactions with various polarized and unpolarized
alkenes,3a,b,c allenes,3d all carbon dienes,3e enamines,3f,g,h
and enol ethers.3i In contrast, there are not many such reports
of the cycloadditions of nitrosoalkenes with carbon–nitrogen
doublebond.4 Mackayet al.5 reported an unusual [3+2] cyclo-
addition of a-nitrosoalkenes with carbon–nitrogen double
bonds of oxazines and failed to observe such a reaction of
nitrosoalkenes with various other cyclic and acyclic com-
pounds bearing a carbon–nitrogen double bond.
The treatment of benzylidene-phenyl-amine with a-phenyl
nitrosoalkenes (entry a; Scheme 1), generated in situ from
the corresponding a-bromooxime and sodium bicarbonate,
in methylene chloride resulted in the exclusive formation
of 3a, a [3+2] cycloadduct. In order to scrutinize the effect
of the electronic nature of a-substituents on nitrosoalkenes,
the reactions of benzylidene-phenyl-amine were repeated
with other nitrosoalkenes viz. p-tolyl and p-nitrophenyl
substituted nitrosoalkenes (entry b and c; Scheme 1). These
reactions also led to the exclusive formation of nitrones 3b
and 3c. This observation got generalized by the sole forma-
tion of nitrones 3 in the reactions of other N-aryl imines
with nitrosoalkenes (Scheme 1). The presence of oxazines 4
even in traces was excluded by analysis of the crude product
with the help of high-resolution 1H NMR spectroscopy.
These experiments indicated that the nature of substituents
on the nitrosoalkenes do not play any significant role in influ-
encing the competitive [3+2] versus [4+2] cycloaddition
pathways as proposed earlier.5 It was felt that the substituents
on imines might be crucial in influencing the pathways fol-
lowed and the distribution of the products formed in their
reactions with nitrosoalkenes. In order to substantiate this
proposition, we considered it worthwhile to examine the re-
actions of N-alkyl imines with nitrosoalkenes. Interestingly,
the reactions of benzylidene-cyclohexyl-amine with all the
Subsequent disclosures from our laboratory have shown
a generalized and unusual [3+2] cycloaddition mode with
various polarized 1,3-diazabuta-1,3-dienes6 resulting in an
easy access to synthetically and biologically significant
imidazoline N-oxides. Few generalizations have been enun-
ciated to account for the nature and preponderance of cyclo-
adducts formed in such reactions. Mackay et al.5 proposed
that the electronic nature of the a-substituents on nitroso-
alkenes determine their preferred conformations, which
in turn become instrumental in controlling the distribution
Keywords: Imidazoline N-oxide; Imidazoles; Oxazines; Theoretical calcula-
tions; Conformations; Isothioureas; Carboxamidines.
* Corresponding author. Tel.: +91 183 2213290; fax: +91 183 2258819;
e-mail: mahajanmohinderp@yahoo.co.in
0040–4020/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.03.047

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5475
R
N
Hc
R1
Ha
Hb
R=aryl
N
R1
H
H
H
O
R2
dry DCM
R.T./stir
+
N
3
R2
N
O
R
R
N
Ha
R
N
R1
Hc
Hc
R1
Ha
Hb
R2
1
2
R=alkyl
Hb
+
O
N
N
O
R2
3
4
n. R=benzyl,R1=C6H4-NMe2(p),R2=C6H4-CH3(p)
o. R=benzyl,R1=C6H4-NMe2(p),R2=C6H4-NO2(p)
p. R=n-butyl,R1=C6H5,R2=C6H5
a. R=C6H5,R1=C6H5,R2=C6H4-CH3(p)
b. R=C6H5,R1=C6H5,R2=C6H5
c. R=C6H5,R1=C6H5,R2=C6H4-NO2(p)
d. R=cyclohexyl,R1=C6H5,R2=C6H5
q. R=n-butyl,R1=C6H5,R2=C6H4-CH3(p)
r. R=n-butyl,R1=C6H5,R2=C6H4-NO2(p)
s. R=iso-propyl,R1=C6H5,R2=C6H5
e. R=cyclohexyl,R1=C6H5,R2=C6H4-CH3(p)
f. R=cyclohexyl,R1=C6H5,R2=C6H4-NO2(p)
g. R=C6H4-CH3(p),R1=C6H5,R2=C6H5
h. R=C6H4-CH3(p),R1=C6H5,R2=C6H4-CH3(p)
i. R=C6H4-CH3(p),R1=C6H5,R2=C6H4-NO2(p)
t. R=iso-propyl,R1=C6H5,R2=C6H4-CH3(p)
u. R=iso-propyl,R1=C6H5,R2=C6H4-NO2(p)
v. R=furyl,R1=C6H5,R2=C6H5
j. R=C6H4-OCH3(p),R1=C6H4-NMe2(p),R2=C6H5
k. R=C6H4-OCH3(p),R1=C6H4-NMe2(p),R2=C6H4-CH3(p)
l. R=C6H4-OCH3(p),R1=C6H4-NMe2(p),R2=C6H4-NO2(p)
m. R=benzyl,R1=C6H4-NMe2(p),R2=C6H5
w. R=furyl,R1=C6H5,R2=C6H4-CH3(p)
x. R=furyl,R1=C6H5,R2=C6H4-NO2(p)
Scheme 1.
forementioned nitrosoalkenes (entry d, e, f) resulted in the
isolation of a mixture of nitrones 3 and oxazines 4 in good
yields; oxazines obtained in higher proportions (40:60).
The reproducible formation of similar mixtures of nitrones
and oxazines in the reactions of other N-alkyl imines with
nitrosoalkenesonceagainsupportedthedeliberationregarding
the decisive role of iminic substituents in the product distri-
bution. Accordingly, the present manuscript is a generalized
andconsummate accountofourearliercommunication8 onthe
effect of substituents on various imines on the mode of cyclo-
additions followed in their reactions with nitrosoalkenes.
mass spectrum of 4m exhibited a molecular ion peak at m/z¼
1
371 for C24H25N3O. In the H NMR of 3m, the methylene
protons exhibited two doublets of doublets at d 3.92, 4.35
(J¼14.1 and 4.2 Hz, Ha) and 4.35 (J¼14.2 and 3.6 Hz, Hb)
corresponding to a CH2 of a nitrone, downfield from the po-
sition d 3.95 in case of oxazine 4m. A doublet of doublet
(J¼4.2 and 3.6 Hz, Hc) corresponding to the CH of nitrone
3f appeared at d 5.49, while that for oxazine 4m appeared
as a singlet at d 6.00. The 13C NMR spectra were also in
agreement with the nitrone and oxazine structures assigned
above to 3m and 4m.
The structures 3 and 4 have been assigned to [3+2] and [4+2]
cycloadducts on the basis of analytical data and spectral
evidences. The products 3m and 4m, for example, were
characterized as [4-(1-benzyl-3-oxy-4-phenyl-2,5-dihydro-
1H-imidazol-2-yl)-phenyl]-dimethyl-amine and [4-(5-ben-
zyl-3-phenyl-5,6-dihydro-4H-[1,2,5]oxadiazin-6-yl)-phenyl]-
dimethyl-amine. The mass spectrum of product 3m, for
example, analyzed for C24H25N3O, exhibited an intense
M-16 peak (m/z¼355) diagnostic of nitrone,3a while the
The nitrones 3 and oxazines 4 are formed in competition and
are not in equilibrium, these were separately shown to be
stable to the reaction conditions, though rearrangements
of oxazines to nitrones9 and nitrones to oxazines10 are well
documented in the literature. The plausible mechanism for
the formation of nitrones and oxazines is illustrated in
Scheme 2. The addition of nitrosoalkene to a C]N bond
is less likely to proceed via a concerted single step as re-
ported earlier.3,11 The reaction presumably proceeds through
R
N
R
N
H
R
Ph
C
N
H
H
Ph
Ph
R= Aryl
N
N
R1
O
R1
N
O
R1
O
5B
3
H
H
5A
H
Ph
+
ON
R1
N
R
N
R
H
R
Ph
H
Ph
R
N
Ph
H
C
N
C
N
H
Ph
1
2
+
R
R=Alkyl
O
R1
O
N
O
N
R1
N
O
N
R1
R1
4
6A
6B
5A
Scheme 2.

5476
A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
O
N
zwitterionic intermediates, 5A and 6A, which are formed
from the cisoid and transoid conformations of the nitroso-
alkenes. These intermediates are interconvertible to other
intermediates 5B and 6B, respectively.
N
O
Me
Me
However, the interconversion between sets of 5A and 6A and
5B and 6B does not seem to be credible as suggested ear-
lier,10,3,4 since this requires rotation around a C]N–O
bond, which becomes stronger after nucleophilic attack,
i.e., changes from a partial double bond in the nitrosoalkene
to a typical double bond in the zwitterionic intermediate. Fi-
nally, the intermediates 5B and 6B cyclize to form the nitro-
nes 3 and oxazines 4, respectively. It seems that formation of
the intermediate 6A is discouraged in the case of aryl-
substituted imines because of the steric repulsions between
the oxygen lone pairs and the p electron cloud on the aryl
substituent. In the case of alkyl-substituted imines; the for-
mation of both intermediates 5A and 6A is possible because
of the reduced steric repulsion between the alkyl group and
the nitrogen or oxygen of the nitrosoalkenes. The above
mechanistic rationale is in agreement with the formation
of both [4+2] and [3+2] cycloadducts in the case of alkyl
imines and exclusively [3+2] adduct in the case of aryl imines.
II
I
O
N
N
O
III
IV
Figure 2. Schematic representation of the conformations of the intermedi-
ates on the reaction path between nitrosoalkenes and imines.
H2C]NMe and cis- and trans-conformers of H2C]
CH–N]O have exhibited that the initial nucleophilic attack
occurs in such a way so as to form intermediates I and II, re-
spectively. The intermediates I and II have been found to be
17.6 and 27.6 kcal/mol higher in energy than the correspond-
ing starting materials. The corresponding final products are
stable by ꢀ37.6 and ꢀ20.2 kcal/mol as compared to the start-
ing materials (Fig. 3) indicating that the formation of six-
membered ring, in the subsequent ring closure step, is more
favorable from kinetic as well as thermodynamic aspects.
The experimental observations and the mechanism proposed
above have been supported by the theoretical calculations at
semi-empirical AM1 and ab initio12 HF/6-31G* levels of
computational analysis implemented in Gaussian series of
programs.13 The schematic representation of the reaction
mechanism studied theoretically is shown in Figure 1.
The schematic representation of the conformations of opti-
mized structures of the intermediates is shown in Figure 2.
The optimized parameters like bond lengths, bond angles,
and dihedral angles of the intermediates are characterized
in Figure 3. The activation energies of the various reactants,
products, and the transition states were estimated from HF/6-
31G* point energy calculations on the structures previously
optimized (Table 1). The relative energies (kcal/mol) of var-
ious intermediates and products bearing N-alkyl and N-aryl
substituents using HF theoretical methods at room tempera-
ture using 6-31+G* basis sets are given in Table 2. All at-
tempts to locate a transition state for a concerted process,
as proposed by Gilchrist3 for the formation of six-membered
ring, between H2C]NH and H2C]CH–N]O at AM1 and
HF/6-31+G* level calculations have revealed that the only
pathway operative in this reaction involves the initial nucleo-
philic attack of iminic nitrogen on the terminal carbon of
nitrosoethylene. Complete optimizations carried out at HF/
6-31+G* theory level on the reaction path involving
Further, HF/6-31+G* calculations for the reaction path in-
volving H2C]N–Ph and H2C]CH–N]O indicated that
the formation of a zwitterionic intermediate is feasible for
the s-trans arrangement of nitrosoethylene. However, such
an intermediate could not be located for the s-cis arrange-
ment. This may be due to the repulsive interactions operating
between the approaching phenyl (p-electrons) and oxygen
(non-bonding electrons) during the initial nucleophilic at-
tack. Due to these repulsive forces, the formation of the cor-
responding zwitterionic intermediate is avoided. However,
in the case of s-trans of nitrosoethylene, the formation of
intermediate IV is conceivable after a twist in the C–C–N–C
angle probably because of the decreased repulsive inter-
actions. The relative energies of the intermediate IV and
the nitrone are 28.6 and ꢀ21.1 kcal/mol with respect to the
corresponding starting materials. Thus, the presence of
a phenyl group on nitrogen does not allow the formation
of zwitterionic intermediate 6, thereby justifying the absence
of the six-membered oxazine in the title reactions of imines
bearing N-aryl substituents. This rationale is further sub-
stantiated by the formation of nitrones and oxazines in the
reactions of benzylidene-benzyl-amine (entry m, n, o) and
benzylidene-furyl-amine (entry v, x, y) with nitrosoalkenes
2, where the above referred electronic repulsions and steric
interactions are supposedly decreased, the phenyl ring being
one carbon atom away from the nitrogen of imine due to the
insertion of a methylene group (Fig. 4).
O
O
N
H
H
R
N
H
H
H
H
R
N
N
H2C
O
H
H
N
N
H
+
R
H
H
P5
ZW3
H
H
N
H
H
H
N
H
H
H
O
1
R
O
H2C
R2
H
H
N
R
a. cis
b. trans
a. R = Me
b. R = Ph
N
R
Solvent effects have not been taken into account in our study.
However, solvents of different polarities might also change
the chemoselectivity of the reaction. However, the solvent
used experimentally, dichloromethane, a non-polar solvent,
P6
ZW4
Figure 1.

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5477
N2-C1=1.252758; C5-C4-N2=111.492389
C3-N2=1.4656284; N6-C5-C4=116.6413079
C4-N2=1.558485; O7-N6-C5=119.2266812
C5-C4=1.4636224; C4-N2-C3-C1=-175.1989112
N6-C5=1.3089472; C5-C4-N2-C3=69.9372295
O7-N6=1.2393158; N6-C5-C4-N2=-93.2134719
C3-N2-C1=122.39158; O7-N6-C5-C4=177.5004877
C4-N2-C3=115.4419577
I
C1-N2=1.253924 ; C3-N2-C1=121.6523538
N2-C3=1.518186 ; C4-C3-N2=112.238191
C4-C3=1.4871451; N5-C4-C3=120.9890215
N5-C4=1.2968952; O6-N5-C4=117.6119068
O6-N5=1.2646881; C7-N2-C3=116.6974679
C7-N2=1.4734058; C4-C3-N2-C1=-111.0999956
C7-N2-C3=116.697468; N5-C4-C3-N2=-88.4786299
N2-C3-C4=112.238191;O6-N5-C4-C3=6.0749739
O6-N5-C4-C3=6.0749739;C7-N2-N3-C4=66.1768982
IV
N2-C1=1.2564137; C15-C13=1.3874312
C3-N2=1.4378906; C16-C14=1.3863046
C4-N2=1.6058972; C17-C15=1.3867999
C5-C4=1.4519722; C3-N2-C1=121.538060
N6-C5=1.3147996; C4-N2-C3=117.348833
O7-N6=1.2357110; C5-C4-N2=113.606416
C13-C3=1.3849957; N6-C5-C4=116.527161
C14-C3=1.3856619; O7-N6-C5=119.1016681
C4-N2-C3-C1=-176.3054821;C13-C3-N2-C1=83.3302754
C5-C4-N2-C3=-173.3125322;C16-C14-C3-N2=1.3863045
N6-C5-C4-N2=-86.9930372; C17-C15-C13-C3=-0.4286934
O7-N6-C5-C4=177.5699184
II
Figure 3. Three dimensional representation of the geometries of the intermediates I, II, and IV (III does not exist) optimized at HF/6-31+G* theory level.
would not have any significant influence on the activation
energies (Table 3).
Table 1. Yields of nitrones 3 and oxazines 4 in Scheme 1
Entry no. 3 (Yield %) 4 (Yield %) Entry no. 3 (Yield %) 4 (Yield %)
The results presented above are in agreement with the earlier
a
b
c
d
e
f
g
h
i
79
78
73
35
32
34
75
80
78
85
81
88
—
—
—
53
48
51
—
—
—
—
—
—
m
n
o
p
q
r
s
t
u
v
w
x
37
30
36
34
30
31
35
37
31
34
31
34
55
50
54
56
50
53
47
48
52
49
54
50
report regarding the exclusive formation of nitrones, i.e.,
[3+2] adducts in the reactions of nitrosoalkenes with N-
aryl-formamidines.6a
In continuation of these studies, it was felt worthwhile to ex-
amine the effect of substituents on carbon of imines in such
reactions. In this series, the reactions of N-aryl-benzamidines
with nitrosoalkenes yielding imidazoles have already been
studied in our laboratory. In-depth study of these reactions
has been explored by investigating these reactions with
j
k
l

5478
A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
Table 2. Absolute energies (ZPE corrected values that has been scaled by a factor of 0.9153 for HF level) of various reactants, intermediates and products at rt
Strs
HF/6-31+G*
ZPVE
Scaling factor (0.9153)
Total energy
R1a
R1b
R2a
R2b
ZW3a
ZW3b
ZW4a
ZW4b
P5a
ꢀ133.0655661
ꢀ323.5871725
ꢀ206.6777504
ꢀ206.6857993
ꢀ339.7067992
ꢀ530.2269237
—
ꢀ339.7152183
ꢀ339.7829033
ꢀ530.3061588
ꢀ339.8031696
ꢀ530.3208283
0.073537
0.130540
0.052863
0.053289
0.132047
0.187762
—
0.133285
0.136773
0.193126
0.137465
0.193775
0.067308416
0.119483262
0.048385504
0.048775422
0.12086219
0.171858559
—
0.121995761
0.125188327
0.176768228
0.125821715
0.177362258
ꢀ132.9982577
ꢀ323.4676892
ꢀ206.629402
ꢀ206.6364239
ꢀ339.5859366
ꢀ530.0550651
—
ꢀ339.5932225
ꢀ339.657715
ꢀ530.1293906
ꢀ339.6773479
ꢀ530.143466
P5b
P6a
P6b
R1
40
H2N
H
H
R1
N
28.6
Dry DCM
R.T./stir
R2
+
N
30
20
N
O
N
27.6
17.6
R2
H
R
R
2
7
8
10
a. R = H, R1 = SCH3, R2 = CH3
b. R = CH3, R1 = SCH3, R2 = CH3
c. R = CH3, R1 = SCH3, R2 = NO2
0
0
d. R = CH3, R1 = Piperidine, R2 = NO2
e. R = H, R1 = morpholine, R2 = NO2
f. R = CH3, R1 = pyrrollidine, R2 = CH3
-10
-20
-30
-40
-50
-20.2
-21.1
Scheme 3.
-37.6
Table 4. Yields of imidazoles 8 in Scheme 3
Entry no.
Yield %
Zwitterionic intermediates
8a
8b
8c
8d
8e
8f
78
80
81
80
81
85
Figure 4. Potential energy surface showing the relative energy of zwitter-
ionic intermediates on the reaction path between nitrosoalkene and imine.
The path involving intermediate I leads to the formation of oxazine, the
path involving intermediates II and IV lead to the formation of nitrones.
Path involving III, which should have led to an oxazine, could not be traced
due of the instability of intermediate III on PE surface.
1. These observations are at variance with the earlier re-
ports by Mackay et al. that nitrosoalkenes did not react
with the carbon–nitrogen double bonds of N,N-di-
methyl-N0-phenyl-benzamidine and 1-phenyl-ethanone
O-methyl-oxime.
imines bearing polar donating amines and thiomethyl at car-
bon of imines, i.e., N-aryl-secondary amine-carboxamidines
commonly known as guanidines and 2-methyl-1-aryl-iso-
thioureas 7.
2. The earlier reported reactions of N-aryl-benzamidines
with nitrosoalkenes leading to the formation of imida-
zoles involve very cumbersome experimental proce-
dures and the use of iron carbonyls.10
Interestingly, these reactions also resulted in the exclusive
isolation of imidazoles 8 in very good yields (Scheme 3,
Table 4), characterized on the basis of spectral and analytical
evidences (Table 4).
It is possible to discern various possible mechanistic path-
ways to the formation of imidazoles in this case. The
The one pot synthesis of imidazoles reported here assumes
significance because:
Table 3. Relative energies (kcal/mol) of various intermediates and products bearing alkyl and aryl substituents using HF theoretical methods at rt using 6-31+G*
basis sets
Reaction
Relative energies of zwitterionic intermediates
Relative energies of products formed
Before adding ZPVE After adding ZPVE
Before adding ZPVE
After adding ZPVE
Me–N]CH2+cis H2C]CH–N]O
Me–N]CH2+trans H2C]CH–N]O
Ph–N]CH2+trans H2C]CH–N]O
17.6 (I)
27.6 (II)
28.6 (IV)
21.6 (I)
30.78 (II)
30.59 (IV)
ꢀ37.6 (I)
ꢀ20.2 (II)
ꢀ21.1 (IV)
ꢀ31.2 (I)
ꢀ15.86 (II)
ꢀ14.45 (IV)

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5479
plausible mechanism, consistent with the one prescribed ear-
lier for the reaction of benzamidines with nitrosoalkenes,6a,b
is depicted in Scheme 4.
H
H
O
N
DCM/
stir/ rt
R
R1
N
S
N
O
+
R1
R
H
Ar
R1
Ar
R1
12
2
H2N
O
N
13
N
Path I
+
2
N
NH2
R1 = H
a. R = pyrrolidine, R1 = H
b. R = piperidine, R1 = H
c. R = morpholine, R1 = H
C6H4R2-p
7
H
N
H
N
H
N
Path II
9
R =
O
Ar
N
Scheme 5.
Ar
R1
Ph
H
N
H
HN
C6H4-R2-p
N
Table 5. Yields of imidazole-N-oxides 16 in Scheme 5
C6H4-R2-p
N
HN
Entry no.
Yield %
OH
OH
10
16a
16b
16c
77
80
79
11
- NH2OH
Ar
acterized as 1,4-diphenyl-2-pyrrolidin-1-yl-1H-imidazole
and analyzed for C19H19N3O exhibited two multiplets at
d 1.79 and 3.30 corresponding to the pyrrolidine protons. A
characteristic singlet corresponding to olefenic proton ap-
peared at d 6.88. The 13C NMR spectral data is in perfect con-
sistent with the suggested structure. The mass spectra of the
compound showed a molecular ion peak (M+) at m/z: 305.
R1
N
H
N
C6H4-R2-p
8
Scheme 4.
The most plausible mechanism for the formation of imida-
zole-N-oxides 13 has been depicted in Scheme 6. It is
assumed that the nitrogen atom of the S-allylated imine 12
attacks the electrophilic carbon of nitrosoalkene 2, as ex-
pected, to form an intermediate 14, which then cyclizes to
form another intermediate 15. This intermediate 15 after
the elimination of a molecule of allyl thiol leads to the
formation of 13.
The reaction may lead to the initial formation of 2-amino-N-
oxide intermediate 9, which probably being unstable is
transformed to another intermediate 10. The intermediate
10 then cyclizes, as shown, to yield another intermediate
11, which ultimately undergoes elimination of NH2OH to
yield the imidazoles 8. The formation of 8 in this case could
also be explained via initial displacement of halide from
a-chlorooxime leading to the intermediate 10, which as
described above then yields 8 via 11.
H
H
In order to authenticate the synthetic versatility of these re-
actions, it was felt that the presence of a suitably disposed
dipolarophile in the molecular structure might result in
intramolecular 1,3-dipolar cycloadditions of the generated
nitrone. Keeping this in view, we have examined the
reactions of S-allylated imines 12 with nitrosoalkenes. In-
terestingly, the reactions of N-phenyl-secondaryamino-1-
carboximidothioic acid allyl ester 12a–d with nitrosoalkenes
2 following the procedure described earlier resulted in the
formation of imidazole-N-oxides 13 in good yields (Table
5), instead of the expected dipolar adducts (Scheme 5).
The formation of the imidazole-N-oxides 13 in these reac-
tions is at odds with our earlier assumption that the allylated
nitrones 15 formed above will be stable enough so as to
follow intramolecular 1,3-dipolar cycloadditions utilizing
the S-allyl moiety thus leading to the formation of tricyclic
heterocycle 16 (Table 5).
R2
N
S
O
N
N
N
N
O
R2
+
S
N
14
2
12
H
H
O
N
R2
SH
N
R2
S
N
N
N
N
O
15
13
N
N
N
H
N
H
H
H
S
S
O
H
N
N
The products formed 13 were characterized as imidazoles on
the basis of spectral and analytical data. The 1H NMR spec-
trum of the products showed the absence of allylic function as
well as the methylene protons and the presence of a character-
istic olefenic proton. The compound 13a, for example, char-
R2
R2
O
H
H
16
15
Scheme 6.

5480
A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
In view of the above observations, it is generalized that the
aryl imines cycloaddition to nitrosoalkenes in a [3+2] man-
ner, while alkyl imines cycloaddition to nitrosoalkenes in
competitive [3+2] and [4+2] manner. It may be inferred
that the substituents on nitrogen as well as carbon atoms
of simple and functionalized imines play a pivotal role in de-
termining the mechanistic pathways and products formed in
their reactions with nitrosoalkenes.
166 ꢂC; [Found: C, 80.49; H, 6.21; N, 11.62. C22H20N2O re-
quires C, 80.46; H, 6.14; N, 11.69%]; nmax/cmꢀ1 (KBr):
1218 (N–O), 1545, 1595 (C]N); dH (200 MHz): d 2.28 (s,
3H, –CH3), 4.93 (dd, J¼14.1 and 2.4 Hz, 1H, –CH2), 5.17
(dd, J¼14.1 and 5.2 Hz, 1H, –CH2), 6.20 (dd, J¼2.4 and
5.2 Hz, 1H, methine), 6.60 (d, J¼8.2 Hz, 2H, ArH), 7.13
(d, J¼8.2 Hz, 2H, ArH), 7.49–7.65 (m, 6H, ArH), 8.25–
8.43 (m, 4H, ArH); 13C NMR: 21.1 (CH3), 57.4 (CH2),
94.3 (methine), 118.9, 122.1, 124.2, 125.7, 127.9, 133.5,
134.1, 134.9, 136.3, 139.1, 141.8, 148.2, and 153.1; m/z:
328 (M+) and 312 (M+ꢀ16).
These cycloaddition reactions offer a remarkable practical
ingress to a diversity of functional and synthetically flexible
nitrogen containing molecular assemblies having biological
and pharmacological significance.14
2.3.2. 1,2,4-Triphenyl-2,5-dihydro-1H-imidazole 3-oxide
(3b). White crystalline solid; yield 78%; mp 140–141 ꢂC;
[Found: C, 80.18; H, 5.80; N, 8.98. C21H18N2O requires C,
80.23; H, 5.77; N, 8.91%]; nmax/cmꢀ1 (KBr): 1219 (N–O),
1547 (C]N), 1589 (C]N); dH (200 MHz): d 4.88 (dd,
J¼14.2 and 2.4 Hz, 1H, –CH2), 5.16 (dd, J¼14.2 and
5.2 Hz, 1H, –CH2), 6.18 (dd, J¼2.4 and 5.3 Hz, 1H,
methine), 6.56–6.84 (m, 3H, ArH), 7.18–7.47 (m, 6H,
ArH), 7.60–7.62 (m, 3H, ArH), 8.32–8.35 (m, 3H, ArH);
13C NMR: 58.1 (CH2), 89.3 (CH), 120.2, 121.1, 123.2,
124.7, 126.8, 128.5, 134.2, 135.2, 136.3, 138.3, 140.2,
147.2, and 152.1; m/z: 314 (M+) and 298 (M+ꢀ16).
2. Experimental
2.1. General
Melting points were determined by open capillary method
using Veego Precision Digital Melting Point apparatus
(MP-D) and are uncorrected. IR spectra were recorded on a
Shimadzu D-8001 spectrophotometer. 1H NMR spectra
were recorded in deuterochloroform with Brucker AC-E
200 (200 MHz) and AC-E 300 (300 MHz) spectrometers
using TMS as internal standard. Chemical shift values are
expressed as d (parts per million) downfield from TMS and
J values are in hertz. Splitting patterns are indicated as s: sin-
glet, d:doublet, t:triplet, m:multiplet, q:quartet andbr:broad
peak. 13C NMR spectra were also recorded on a Brucker
AC-200E (50.4 MHz) or Brucker AC-300E (75.0 MHz)
spectrometers in a deuterochloroform using TMS as internal
standard. Mass spectra were recorded on Shimadzu GCMS-
QP-2000 mass spectrometer. Elemental analyses were per-
formed on Heraus CHN-O-Rapid Elemental Analyzer.
2.3.3. 4-(4-Nitro-phenyl)-1,2-diphenyl-2,5-dihydro-1H-
imidazole 3-oxide (3c). White crystalline solid; yield
73%; mp 181–182 ꢂC; [Found: C, 70.22; H, 4.84; N,
11.62. C21H17N3O3 requires C, 70.18; H, 4.77; N,
11.69%]; nmax/cmꢀ1 (KBr): 1219 (N–O), 1545, 1592
(C]N); dH (200 MHz): d 5.18 (dd, J¼14.4 and 2.9 Hz,
1H, –CH2), 5.46 (dd, J¼14.4 and 5.4 Hz, 1H, –CH2), 6.49
(dd, J¼2.9 and 5.4 Hz, 1H, methine), 7.05–7.52 (m, 5H,
ArH), 7.65–7.88 (m, 5H, ArH), 8.54 (d, J¼9.0 Hz, 2H,
ArH), 8.74 (d, J¼9.0 Hz, 2H, ArH); 13C NMR: 56.3
(CH2), 94.4 (methine), 118.2, 120.9, 123.3, 125.1, 125.9,
133.2, 133.8, 134.4, 135.1, 137.6, 140.5, 145.2, and 152.2;
m/z: 359 (M+) and 343 (M+ꢀ16).
2.2. Starting materials
All the acyclic imines (Schiff’s bases)15a 1,2-methyl-1-
aryl-isothioureas 7a–c,15b N-aryl-secondary amine-carbox-
amidines 7d–f,15b S-allylated imines 12, and bromooximes
of acetophenone, p-nitroacetophenone and p-methylaceto-
phenone 215c were prepared by reported procedures.
2.3.4. 1-Cyclohexyl-2,4-diphenyl-2,5-dihydro-1H-imida-
zole 3-oxide (3d). White crystalline solid; yield 35%; mp
165–166 ꢂC; [Found: C, 78.78; H, 7.50; N, 8.71.
C21H24N2O requires C, 78.71; H, 7.55; N, 8.74%]; nmax
/
cmꢀ1 (KBr): 1218 (N–O), 1525, 1598 (C]N); dH
(200 MHz): d 1.26–2.03 (m, 10H, cyclohexyl), 2.71–2.73
(m, 1H, –CH, cyclohexyl), 4.32 (dd, J¼14.7 and 3.6 Hz,
1H, –CH2), 4.66 (dd, J¼14.4 and 4.2 Hz, 1H, –CH2),
5.78 (dd, J¼3.6 and 4.2 Hz, 1H, methine), 7.36–7.53 (m,
6H, ArH), 7.69–7.74 (m, 2H, ArH), 8.33–8.37 (m, 2H,
ArH); 13C NMR: 25.5, 25.7, 30.7, 31.2, 31.9, 37.8, 52.9
(CH2), 90.7 (methine), 122.5, 126.3, 129.1, 129.9, 132.7,
136.8, 139.0, 142.9, and 163.8; m/z: 320 (M+) and 304
(M+ꢀ16).
2.3. Reactions of acyclic imines (Schiff’s bases) with
a-nitrosoalkenes. General procedure for nitrones 3
and oxazines 4
A solution of Schiff’s base 1 (4 mmol) and a-bromooxime 2
(4.2 mmol) in dry CH2Cl2 was stirred at rt in the presence of
anhydrous sodium bicarbonate (6 mmol) for 24–25 h. The
deposited salt and the excess of sodium bicarbonate were
filtered off and washed with small portions (2ꢁ10 ml)
of CH2Cl2. The combined filtrates were washed with water,
extracted with dichloromethane, dried over Na2SO4, and
concentrated under reduced pressure. The nitrones 3 and
oxazines 4 were isolated and purified with the help of
column chromatography on 60–120 mesh silica gel. The
nitrones and oxazines were recrystallized from benzene–
hexane (2:1) and EtOAc–hexane (1:5), respectively.
2.3.5. 5-Cyclohexyl-3,6-diphenyl-5,6-dihydro-4H-
[1,2,5]oxadiazine (4d). White crystalline solid; yield 53%;
mp 141–142 ꢂC; [Found: C, 78.76; H, 7.48; N, 8.76.
C21H24N2O requires C, 78.71; H, 7.55; N, 8.74%]; nmax
/
cmꢀ1 (KBr): 1620 (C]N); dH (200 MHz): d 1.21–2.03
(m, 10H, cyclohexyl), 2.82–2.85 (m, 1H, –CH, cyclohexyl),
3.59 (s, 2H, –CH2), 6.00 (s, 1H, methine), 7.21–7.52 (m, 5H,
ArH), 7.73–8.10 (m, 5H, ArH); 13C NMR: 25.6, 25.7, 25.8,
31.1, 31.9, 38.2, 61.7 (CH2), 89.2 (methine), 123.7, 124.9,
2.3.1. 1,2-Diphenyl-4-p-tolyl-2,5-dihydro-1H-imidazole
3-oxide (3a). White crystalline solid; yield 79%; mp 165–

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5481
126.2, 127.8, 128.4, 137.7, 140.2, 147.7, and 153.5; m/z:
334 (M+).
J¼14.1 and 5.0 Hz, 1H, –CH2), 6.20 (dd, J¼3.2 and
5.0 Hz, 1H, methine), 6.52 (d, J¼8.4 Hz, 2H, ArH), 7.04
(d, J¼8.4 Hz, 2H, ArH), 7.42–7.48 (m, 6H, ArH), 7.62–
7.63 (m, 2H, ArH), 8.34–8.35 (m, 2H, ArH); 13C NMR:
24.9, 55.1 (CH2), 89.2 (methine), 118.2, 121.2, 122.9,
123.6, 126.2, 133.1, 133.9, 134.1, 135.2, 137.5, 141.1,
147.2, and 152.1; m/z: 328 (M+) and 312 (M+ꢀ16).
2.3.6. 1-Cyclohexyl-2-phenyl-4-p-tolyl-2,5-dihydro-1H-
imidazole 3-oxide (3e). White crystalline solid; yield
32%; mp 175–176 ꢂC; [C, 79.05; H, 7.90; N, 8.29.
C22H26N2O requires C, 79.00; H, 7.84; N, 8.38%]; nmax
/
cmꢀ1 (KBr): 1220 (N–O), 1545, 1591 (C]N); dH
(200 MHz): d 1.15–1.89 (m, 10H, cyclohexyl), 2.43 (s, 3H,
CH3), 2.83–2.86 (m, 1H, –CH, cyclohexyl), 3.95 (dd,
J¼14.1 and 3.2 Hz, 1H, –CH2), 4.61 (dd, J¼14.1 and
4.5 Hz, 1H, –CH2), 5.70 (dd, J¼3.2 and 4.5 Hz, 1H,
methine), 6.59 (d, J¼8.1 Hz, 2H, ArH), 7.03 (d, J¼8.1 Hz,
2H, ArH), 7.12–7.52 (m, 5H, ArH); 13C NMR: 20.9, 25.1,
25.4, 25.8, 30.7, 31.1, 38.7, 52.9 (CH2), 89.1 (CH), 120.6,
124.2, 126.1, 127.3, 128.1, 132.2, 134.3, 139.4, and 161.7;
m/z: 334 (M+) and 318 (M+ꢀ16).
2.3.11. 2-Phenyl-1,4-di-p-tolyl-2,5-dihydro-1H-imidazole
3-oxide (3h). White crystalline solid; yield 80%; mp 135–
136 ꢂC; [Found: C, 80.72; H, 6.40; N, 8.22. C23H22N2O re-
quires C, 80.67; H, 6.48; N, 8.18%]; nmax/cmꢀ1 (KBr): 1220
(N–O), 1545, 1601 (C]N); dH (200 MHz): d 2.21 (s, 3H,
–CH3), 2.25 (s, 3H, CH3), 4.91 (dd, J¼14.1 and 3.2 Hz,
1H, –CH2), 5.17 (dd, J¼14.1 and 5.2 Hz, 1H, –CH2), 6.22
(dd, J¼3.2 and 5.2 Hz, 1H, methine), 6.48 (d, J¼8.6 Hz,
2H, ArH), 7.02 (d, J¼8.6 Hz, 2H, ArH), 7.35–7.51 (m,
9H, ArH); 13C NMR: 24.5, 25.1, 55.2 (CH2), 90.1 (methine),
118.7, 120.5, 123.2, 123.8, 124.5, 125.9, 134.1, 134.9,
136.4, 139.1, 140.1, 146.5, and 153.1; m/z: 342 (M+) and
326 (M+ꢀ16).
2.3.7. 5-Cyclohexyl-6-phenyl-3-p-tolyl-5,6-dihydro-4H-
[1,2,5]oxadiazine (4e). White crystalline solid; yield
48%; mp 153–154 ꢂC; [Found C, 78.97; H, 7.91; N, 8.45.
C22H26N2O requires C, 79.00; H, 7.84; N, 8.38%]; nmax
/
cmꢀ1 (KBr): 1621 (C]N); dH (200 MHz): d 1.21–2.07
(m, 10H, cyclohexyl), 2.39 (s, 3H, CH3), 2.84–2.87 (m, 1H,
–CH, cyclohexyl), 3.61 (s, 2H, –CH2), 5.99 (s, 1H, methine),
6.58 (d, J¼8.2 Hz, 2H, ArH), 7.01 (d, J¼8.0 Hz, 2H, ArH),
7.10–7.46 (m, 5H, ArH); 13C NMR: 21.0, 25.4, 25.7, 25.8,
30.9, 31.2, 38.3, 61.4 (CH2), 89.3 (CH), 121.1, 123.9, 126.0,
127.8, 128.3, 133.0, 134.5, 138.3, and 153.6; m/z: 334 (M+).
2.3.12. 4-(4-Nitro-phenyl)-2-phenyl-1-p-tolyl-2,5-di-
hydro-1H-imidazole 3-oxide (3i). White crystalline solid;
yield 78%; mp 160–161 ꢂC; [Found: C, 70.82; H, 5.16; N,
11.29. C22H19N3O3 requires C, 70.76; H, 5.13; N,
11.25%]; nmax/cmꢀ1 (KBr): 1221 (N–O), 1547, 1597
(C]N); dH (200 MHz): d 2.20 (s, 3H, –CH3), 5.02 (dd,
J¼14.1 and 2.8 Hz, 1H, –CH2), 5.27 (dd, J¼14.1 and
5.4 Hz, 1H, –CH2), 6.30 (dd, J¼2.8 and 5.4 Hz, 1H,
methine), 6.61 (d, J¼8.4 Hz, 2H, ArH), 7.13 (d, J¼8.4 Hz,
2H, ArH), 7.50–7.70 (m, 5H, ArH), 8.39 (d, J¼8.9 Hz,
2H, ArH), 8.59 (d, J¼8.9 Hz, 2H, ArH); 13C NMR: 20.1
(CH3), 52.5 (CH2), 90.1 (methine), 112.9, 117.3, 123.6,
127.2, 127.8, 127.9, 128.6, 129.7, 129.9, 132.5, 141.3,
147.7, and 152.2; m/z: 373 (M+) and 357 (M+ꢀ16).
2.3.8. 1-Cyclohexyl-4-(4-nitro-phenyl)-2-phenyl-2,5-di-
hydro-1H-imidazole 3-oxide (3f). White crystalline solid;
yield 34%; mp 169–170 ꢂC; [Found C, 69.08; H, 6.31; N,
11.52. C21H23N3O3 requires C, 69.02; H, 6.34; N, 11.50%];
nmax/cmꢀ1 (KBr): 1221 (N–O), 1547, 1595 (C]N); dH
(200 MHz): d 1.18–1.95 (m, 10H, cyclohexyl), 2.65–2.66
(m, 1H, –CH, cyclohexyl), 3.98 (dd, J¼14.7 and 3.6 Hz, 1H,
–CH2), 4.62 (dd, J¼14.7 and 4.2 Hz, 1H, –CH2), 5.72 (dd,
J¼3.6 and 4.2 Hz, 1H, methine), 7.43–7.61 (m, 5H, ArH),
8.27 (d, J¼8.6 Hz, 2H, ArH), 8.42 (d, J¼8.6 Hz, 2H, ArH);
13C NMR: 25.3, 25.5, 25.8, 30.9, 31.4, 38.8, 53.1 (CH2),
89.9 (methine), 123.7, 127.2, 128.5, 129.8, 133.1, 136.7,
138.0, 148.1, and 161.9; m/z: 365 (M+) and 349 (M+ꢀ16).
2.3.13. {4-[1-(4-Methoxy-phenyl)-3-oxy-4-phenyl-2,5-di-
hydro-1H-imidazol-2-yl]-phenyl}-dimethyl-amine (3j).
Yellow crystalline solid; yield 85%; mp 139–140 ꢂC;
[Found: C, 74.45; H, 6.45; N, 10.82. C24H25N3O2 requires
C, 74.39; H, 6.50; N, 10.84%]; nmax/cmꢀ1 (KBr): 1223
(N–O), 1546, 1589 (C]N); dH (200 MHz): d 2.91 [(s, 6H,
–N(CH3)2], 3.72 (s, 3H, –OCH3), 4.76 (dd, J¼14.1 and
3.2 Hz, 1H, –CH2), 5.05 (dd, J¼14.1 and 5.5 Hz, 1H,
–CH2), 6.00 (dd, J¼3.2 and 5.5 Hz, 1H, methine), 6.53 (d,
J¼8.8 Hz, 2H, ArH), 6.69 (d, J¼8.7 Hz, 2H, ArH), 6.79
(d, J¼8.8 Hz, 2H, ArH), 7.20–8.24 (m, 7H, ArH); 13C
NMR: 40.4 (NMe2), 52.5 (–CH2–), 55.6 (OCH3), 90.6
(methine), 112.1, 113.8, 115.0, 122.2, 124.1, 128.1, 128.9,
133.2, 135.8, 138.5, 148.9, 152.1, and 153.5; m/z: 387
(M+) and 371 (M+ꢀ16).
2.3.9. 5-Cyclohexyl-3-(4-nitro-phenyl)-6-phenyl-5,6-di-
hydro-4H-[1,2,5]oxadiazine (4f). White crystalline solid;
yield 51%; mp 153–154 ꢂC; [Found: C, 69.10; H, 6.30; N,
11.55. C21H23N3O3 requires C, 69.02; H, 6.34; N,
11.50%]; nmax/cmꢀ1 (KBr): 1620 (C]N); dH (200 MHz):
d 1.21–2.05 (m, 10H, cyclohexyl), 2.85–2.87 (m, 1H,
–CH, cyclohexyl), 3.62 (s, 2H, –CH2), 6.00 (s, 1H, methine),
7.30–7.57 (m, 5H, ArH), 7.73 (d, J¼8.5 Hz, 2H, ArH), 8.19
(d, J¼8.5 Hz, 2H, ArH); 13C NMR: 25.5, 25.6, 25.7, 31.1,
31.4, 38.9 (–CH, cyclohexyl), 61.6 (–CH2), 89.4 (methine),
123.6, 125.2, 126.5, 128.2, 128.5, 138.0, 140.1, 148.2, and
153.5; m/z: 365 (M+).
2.3.14. {4-[1-(4-Methoxy-phenyl)-3-oxy-4-p-tolyl-2,5-di-
hydro-1H-imidazol-2-yl]-phenyl}-dimethyl-amine (3k).
Yellow crystalline solid; yield 81%; mp 177–178 ꢂC;
[Found: C, 74.84; H, 6.75; N, 10.45. C25H27N3O2 requires
C, 74.79; H, 6.78; N, 10.47%]; nmax/cmꢀ1 (KBr): 1225
(N–O), 1547, 1595 (C]N); dH (200 MHz): d 2.35 (s, 3H,
CH3), 2.91 [(s, 6H, –N(CH3)2], 3.72 (s, 3H, –OCH3), 4.71
(dd, J¼14.2 and 3.2 Hz, 1H, –CH2), 5.10 (dd, J¼14.2 and
5.4 Hz, 1H, –CH2), 6.03 (dd, J¼3.2 and 5.4 Hz, 1H,
methine), 6.62 (d, J¼8.8 Hz, 2H, ArH), 6.71 (d, J¼8.8 Hz,
2.3.10. 2,4-Diphenyl-1-p-tolyl-2,5-dihydro-1H-imidazole
3-oxide (3g). White crystalline solid; yield 75%; mp 175–
176 ꢂC; [Found: C, 80.50; H, 6.16; N, 8.48. C22H20N2O re-
quires C, 80.46; H, 6.14; N, 8.53%]; nmax/cmꢀ1 (KBr): 1221
(N–O), 1545, 1600 (C]N); dH (200 MHz): d 2.25 (s, 3H,
–CH3), 4.88 (dd, J¼14.1 and 3.2 Hz, 1H, –CH2), 5.14 (dd,

5482
A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
2H, ArH), 6.91 (d, J¼8.8 Hz, 2H, ArH), 6.99 (d, J¼8.8 Hz,
2H, ArH), 7.27 (d, J¼8.8 Hz, 2H, ArH), 7.43 (d,
J¼8.8 Hz, 2H, ArH); 13C NMR: 21.6 (CH3), 40.3 (NMe2),
52.8 (–CH2–), 55.5 (OCH3), 90.6 (methine), 113.9, 114.3,
115.2, 122.3, 126.9, 127.5, 128.1, 129.1, 134.6, 135.7,
140.2, 146.1, and 153.1; m/z: 401 (M+) and 385 (M+ꢀ16).
J¼4.1 and 3.5 Hz, 1H, methine), 6.78 (d, J¼8.4 Hz, 2H,
ArH), 6.88 (d, J¼8.6 Hz, 2H, ArH), 6.99 (d, J¼8.6 Hz,
2H, ArH), 7.12–7.89 (m, 7H, ArH); 13C NMR: 20.9 (CH3),
41.1 (NMe2), 52.9 (CH2, benzylic), 56.1 (CH2), 94.1
(methine), 112.5, 120.9, 122.5, 125.5, 128.1, 128.8, 131.2,
134.1, 134.7, 138.2, 146.1, 151.9, and 152.9; m/z: 385
(M+) and 369 (M+ꢀ16).
2.3.15. {4-[1-(4-Methoxy-phenyl)-4-(4-nitro-phenyl)-3-
oxy-2,5-dihydro-1H-imidazol-2-yl]-phenyl}-dimethyl-
amine (3l). Red crystalline solid; yield 88%; mp 166–
167 ꢂC; [Found: C, 66.63; H, 5.52; N, 12.99. C24H24N4O4
requires C, 66.69; H, 5.59; N, 12.96%]; nmax/cmꢀ1 (KBr):
1220 (N–O), 1542, 1591 (C]N); dH (200 MHz): d 2.96
[(s, 6H, –N(CH3)2], 3.73 (s, 3H, –OCH3), 4.79 (dd, J¼14.1
and 3.1 Hz, 1H, –CH2), 5.15 (dd, J¼14.1 and 5.4 Hz, 1H,
–CH2), 6.08 (dd, J¼3.1 and 5.4 Hz, 1H, methine), 6.59 (d,
J¼8.8 Hz, 2H, ArH), 6.70 (d, J¼8.7 Hz, 2H, ArH), 6.81
(d, J¼8.8 Hz, 2H, ArH), 7.44 (d, J¼8.7 Hz, 2H, ArH),
8.29 (d, J¼8.8 Hz, 2H, ArH), 8.49 (d, J¼8.8 Hz, 2H,
ArH); 13C NMR: 40.3 (NMe2), 52.7 (–CH2–), 55.5
(OCH3), 90.7 (methine), 112.1, 113.7, 114.9, 122.2, 123.9,
127.2, 128.8, 132.9, 135.2, 138.3, 147.8, 151.7, and 152.8;
m/z: 432 (M+) and 416 (M+ꢀ16).
2.3.19. [4-(5-Benzyl-3-p-tolyl-5,6-dihydro-4H-[1,2,5]oxa-
diazin-6-yl)-phenyl]-dimethyl-amine (4n). White crystal-
line solid; yield 50%; mp 142–143 ꢂC; [Found: C, 77.92;
H, 7.02; N, 10.93. C25H27N3O requires C, 77.89; H, 7.06; N,
10.90%]; nmax/cmꢀ1 (KBr): 1624 (C]N); dH (200 MHz):
d 2.32 (s, 3H, CH3), 2.90 [(s, 6H, –N(CH3)2], 3.23 (d,
J¼13.8 Hz, 1H, benzylic), 3.95 (s, 2H, CH2, oxazine), 4.15
(d, J¼13.8 Hz, 1H, benzylic), 5.98 (s, 1H, methine), 6.75
(d, J¼8.0 Hz, 2H, ArH), 6.95 (d, J¼8.0 Hz, 2H, ArH), 7.18
(d, J¼8.5 Hz, 2H, ArH), 7.21–7.40 (m, 5H, ArH), 7.48 (d,
J¼8.5 Hz, 2H, ArH); 13C NMR: 20.9 (CH3), 40.3 (NMe2),
52.5 (CH2, oxazine), 54.3 (CH2, benzylic), 93.1 (methine),
114.1, 119.1, 123.5, 126.2, 129.1, 129.9, 132.2, 134.1,
135.2, 137.7, 146.1, 152.1, and 153.5; m/z: 385 (M+).
2.3.20. {4-[1-Benzyl-4-(4-nitro-phenyl)-3-oxy-2,5-di-
hydro-1H-imidazol-2-yl]-phenyl}-dimethyl-amine (3o).
White crystalline solid; yield 36%; mp 147–148 ꢂC; [Found:
C, 69.26; H, 5.85; N, 13.39. C24H24N4O3 requires C, 69.21;
H, 5.81; N, 13.45%]; nmax/cmꢀ1 (KBr): 1219 (N–O), 1547,
1595 (C]N); dH (200 MHz): d 2.90 [(s, 6H, –N(CH3)2],
3.62 (d, J¼13.0 Hz, 1H, benzylic), 3.87 (dd, J¼14.0 and
4.6 Hz, 1H, CH2), 4.08 (d, J¼13.0 Hz, 1H, benzylic), 4.36
(dd, J¼14.0 and 3.2 Hz, 1H, CH2), 5.46 (dd, J¼4.6 and
3.2 Hz, 1H, methine), 6.80 (d, J¼8.4 Hz, 2H, ArH), 7.25–
7.36 (m, 5H, ArH), 7.54 (d, J¼8.4 Hz, 2H, ArH), 8.21 (d,
J¼9.0 Hz, 2H, ArH), 8.35 (d, J¼9.0 Hz, 2H, ArH); 13C
NMR: 40.3 (NMe2), 53.9 (–CH2–, benzylic), 56.3 (–CH2);
94.6 (methine), 112.1, 121.2, 123.6, 126.9, 127.7, 128.6,
130.0, 133.3, 133.6, 136.5, 147.6, 151.8, and 152.9; m/z:
416 (M+) and 400 (M+ꢀ16).
2.3.16. [4-(1-Benzyl-3-oxy-4-phenyl-2,5-dihydro-1H-imi-
dazol-2-yl)-phenyl]-dimethyl-amine (3m). Creamish crys-
talline solid; yield 37%; mp 178–179 ꢂC; [Found: C, 77.57;
H, 6.82; N, 11.33. C24H25N3O requires C, 77.60; H, 6.78; N,
11.37%]; nmax/cmꢀ1 (KBr): 1221 (N–O), 1547, 1600
(C]N); dH (200 MHz): d 2.90 [(s, 6H, –N(CH3)2], 3.21
(d, J¼13.5 Hz, 1H, benzylic), 3.92 (dd, J¼14.1 and
4.2 Hz, 1H, CH2), 4.05 (d, J¼13.5 Hz, 1H, benzylic), 4.35
(dd, J¼14.2 and 3.6 Hz, 1H, CH2), 5.49 (dd, J¼4.2 and
3.6 Hz, 1H, methine), 6.81 (d, J¼8.5 Hz, 2H, ArH), 7.31–
7.57 (m, 5H, ArH), 7.62 (d, J¼8.5 Hz, 2H, ArH), 7.95–
8.10 (m, 5H, ArH); 13C NMR: 41.1 (NMe2), 52.7 (CH2,
benzylic), 56.1 (CH2), 94.3 (methine), 112.1, 121.2, 123.6,
126.7, 128.1, 128.7, 129.9, 132.5, 134.1, 136.9, 148.1,
152.1, and 153.2; m/z: 371 (M+) and 355 (M+ꢀ16).
2.3.17. [4-(5-Benzyl-3-phenyl-5,6-dihydro-4H-[1,2,5]oxa-
diazin-6-yl)-phenyl]-dimethyl-amine (4m). White crystal-
line solid; yield 55%; mp 172–173 ꢂC; [Found: C, 77.68; H,
6.82; N, 11.33. C24H25N3O requires C, 77.60; H, 6.78; N,
11.37%]; nmax/cmꢀ1 (KBr): 1621 (C]N); dH (200 MHz):
d 2.92 [(s, 6H, –N(CH3)2], 3.25 (d, J¼13.6 Hz, 1H, benzylic
CH2), 3.95 (s, 2H, CH2, oxazine), 4.09 (d, J¼13.6 Hz, 1H,
benzylic –CH2), 6.00 (s, 1H, methine), 6.78 (d, J¼8.5 Hz,
2H, ArH), 7.15–7.32 (m, 5H, ArH), 7.48 (d, J¼8.5 Hz,
2H, ArH), 7.65–7.98 (m, 5H, ArH); 13C NMR: 40.2
(NMe2), 52.1 (CH2, oxazine), 53.6 (CH2, benzylic), 92.9
(methine), 112.2, 122.7, 123.9, 127.5, 128.3, 129.0, 130.9,
135.5, 137.1, 138.2, 147.1, 152.5, and 153.5; m/z: 371 (M+).
2.3.21. {4-[5-Benzyl-3-(4-nitro-phenyl)-5,6-dihydro-4H-
[1,2,5]oxadiazin-6-yl]-phenyl}-dimethyl-amine (4o). Yel-
low crystalline solid; yield 54%; mp 115–117 ꢂC; [Found:
C, 69.27; H, 5.86; N, 13.39. C24H24N4O3 requires C,
69.21; H, 5.81; N, 13.45%]; nmax/cmꢀ1 (KBr): 1625
(C]N); dH (200 MHz): d 2.95 [(s, 6H, –N(CH3)2], 3.47
(d, J¼14.0 Hz, 1H, benzylic), 3.49 (d, J¼13.9 Hz, 1H,
benzylic), 3.62 (d, J¼5.0 Hz, 1H, –CH2), 3.87 (d, 1H,
J¼5.1 Hz), 5.76 (s, 1H, methine), 6.73 (d, J¼8.8 Hz, 2H,
ArH), 7.27–7.41 (m, 5H, ArH), 7.47 (d, J¼8.7 Hz, 2H,
ArH), 7.70 (d, J¼8.9 Hz, 2H, ArH), 8.17 (d, J¼8.9 Hz,
2H, ArH); 13C NMR: 40.3 (NMe2), 52.1 (CH2, benzylic),
56.1 (–CH2), 91.3 (methine), 112.4, 122.5, 124.1, 127.3,
128.1, 129.1, 131.5, 134.2, 134.8, 137.1, 148.5, 152.5, and
153.2; m/z: 416 (M+).
2.3.18. [4-(1-Benzyl-3-oxy-4-p-tolyl-2,5-dihydro-1H-imi-
dazol-2-yl)-phenyl]-dimethyl-amine (3n). Yellow crystal-
line solid; yield 30%; mp 161–162 ꢂC; [Found: C, 77.94;
H, 7.02; N, 10.87. C25H27N3O requires C, 77.89; H, 7.06;
N, 10.90%]; nmax/cmꢀ1 (KBr): 1225 (N–O), 1548, 1601
(C]N); dH (200 MHz): d 2.32 (s, 3H, CH3), 2.91 [(s, 6H,
–N(CH3)2], 3.56 (d, J¼13.0 Hz, 1H, benzylic), 3.82 (dd,
J¼14.2 and 4.2 Hz, 1H, CH2), 4.06 (d, J¼13.0 Hz, 1H, ben-
zylic), 4.32 (dd, J¼14.2 and 3.6 Hz, 1H, CH2), 5.49 (dd,
2.3.22. 1-Butyl-2,4-diphenyl-2,5-dihydro-1H-imidazole
3-oxide (3p). White crystalline solid; yield 34%; mp 146–
147 ꢂC; [Found: C, 77.60; H, 7.45; N, 9.48. C19H22N2O re-
quires C, 77.52; H, 7.53; N, 9.52%]; nmax/cmꢀ1 (KBr): 1221
(N–O), 1545, 1594 (C]N); dH (200 MHz): d 0.92 (t,
J¼7.4 Hz, 3H, CH3), 1.37–1.65 (m, 4H, 2ꢁCH2), 2.72–
2.81 (m, 2H, CH2), 4.32 (dd, J¼14.7 and 3.6 Hz, 1H,

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5483
CH2), 4.71 (dd, J¼14.7 and 4.2 Hz, 1H, CH2), 5.85 (dd,
J¼3.5 and 4.1 Hz, 1H, methine), 6.99–7.32 (m, 6H, ArH),
7.42–7.59 (m, 4H, ArH); 13C NMR: 14.3, 21.7, 23.9, 45.2,
53.1, 91.2, 122.9, 123.5, 125.9, 127.9, 129.7, 137.9, 141.7,
150.2, and 153.2; m/z: 294 (M+) and 278 (M+ꢀ16).
d 0.94 (t, J¼7.2 Hz, 3H, CH3), 1.39–1.63 (m, 4H,
2ꢁCH2), 2.74–2.82 (m, 2H, CH2), 3.65 (AB quartet,
J¼7.7 Hz, 2H, CH2, oxazine), 5.79 (s, 1H, methine), 7.28–
7.59 (m, 5H, ArH), 7.78 (d, J¼8.8 Hz, 2H, ArH), 8.23 (d,
J¼8.8 Hz, 2H, ArH); 13C NMR: 13.8, 20.2, 29.9, 43.8,
51.5, 91.0, 123.7, 125.4, 126.6, 128.5, 128.6, 137.1, 140.3,
148.3, and 152.1; m/z: 339 (M+).
2.3.23. 5-Butyl-3,6-diphenyl-5,6-dihydro-4H-[1,2,5]oxa-
diazine (4p). White crystalline solid; yield 56%; mp 129–
130 ꢂC; [Found: C, 77.55; H, 7.48; N, 9.47. C19H22N2O re-
quires C, 77.52; H, 7.53; N, 9.52%]; nmax/cmꢀ1 (KBr): 1621
(C]N); dH (200 MHz): d 0.95 (t, 3H, CH3), 1.39–1.63 (m,
4H, 2ꢁCH2), 2.71–2.84 (m, 2H, CH2), 3.89 (AB quartet,
J¼7.7 Hz, 2H, CH2), 5.99 (s, 1H, methine), 6.95–7.32 (m,
5H, ArH), 7.45–7.98 (m, 5H, ArH); 13C NMR: 13.7, 20.2,
32.1, 46.6, 52.1, 91.5, 125.7, 121.9, 124.3, 126.9, 129.9,
140.2, 143.9, 151.1, and 153.1; m/z: 294 (M+).
2.3.28. 1-Isopropyl-2,4-diphenyl-2,5-dihydro-1H-imida-
zole 3-oxide (3s). White crystalline solid; yield 35%; mp
120–121 ꢂC; [Found: C, 77.19; H, 7.12; N, 10.05.
C18H22N2O requires C, 77.11; H, 7.19; N, 9.99%]; nmax/cm
ꢀ1 (KBr): 1225 (N–O), 1545, 1599 (C]N); dH (200 MHz):
d 1.15–1.21 (m, 6H, 2ꢁCH3), 3.19–3.45 (m, 1H, –CH, iso-
propyl), 4.32 (dd, J¼14.7 and 3.6 Hz, 1H, CH2), 4.72 (dd,
J¼14.7 and 4.2 Hz, 1H, CH2), 5.79 (dd, J¼3.6 and 4.2 Hz,
1H, methine), 6.82–7.35 (m, 6H, ArH), 7.51–7.69 (m, 2H,
ArH), 7.92–8.05 (m, 2H, ArH); 13C NMR: 12.3, 22.4, 49.1,
89.7, 127.5, 129.1, 130.2, 130.8, 131.7, 133.5, 134.7,
142.1, and 153.9; m/z: 280 (M+) and 264 (M+ꢀ16).
2.3.24. 1-Butyl-2-phenyl-4-p-tolyl-2,5-dihydro-1H-imida-
zole 3-oxide (3q). White crystalline solid; yield 30%;
mp 155–156 ꢂC; [Found: C, 77.82; H, 7.81; N, 9.13.
C20H24N2O requires C, 77.89; H, 7.84; N, 9.08%]; nmax
/
cmꢀ1 (KBr): 1220 (N–O), 1547, 1596 (C]N); dH
(200 MHz): d 0.92 (t, J¼7.5 Hz, 3H, CH3), 1.38–1.62 (m,
4H, 2ꢁCH2), 2.32 (s, 3H, CH3), 2.73–2.81 (m, 2H, CH2),
4.40 (dd, J¼14.7 and 3.6 Hz, 1H, CH2), 4.79 (dd, J¼14.7
and 4.2 Hz, 1H, CH2), 5.79 (dd, J¼3.6 and 4.2 Hz, 1H,
methine), 6.60 (d, J¼8.5 Hz, 2H, ArH), 7.02 (d, J¼8.5 Hz,
2H, ArH), 7.35–7.61 (m, 5H, ArH); 13C NMR: 14.1, 21.2,
23.5, 46.1, 55.3, 94.3, 121.1, 122.4, 126.3, 128.1, 129.2,
138.7, 142.2, 148.5, and 152.9; m/z:308 (M+) and 292 (M+ꢀ16).
2.3.29. 5-Isopropyl-3,6-diphenyl-5,6-dihydro-4H-[1,2,5]-
oxadiazine (4s). White crystalline solid; yield 47%; mp
101–102 ꢂC; [Found: C, 77.08; H, 7.12; N, 10.06.
C18H22N2O requires C, 77.14; H, 7.19; N, 9.99%]; nmax
/
cmꢀ1 (KBr): 1623 (C]N); dH (200 MHz): d 1.15–1.23
(m, 6H, 2ꢁCH3), 3.21–3.48 (m, 1H, –CH, isopropyl), 3.69
(s, 2H, –CH2, oxazine), 5.99 (s, 1H, methine), 6.75–7.10
(m, 5H, ArH), 7.25–7.95 (m, 5H, ArH); 13C NMR: 11.8,
21.9, 48.8, 89.8, 129.1, 129.7, 130.2, 132.1, 132.9, 134.1,
134.7, 140.7, and 152.1; m/z: 280 (M+).
2.3.25. 5-Butyl-6-phenyl-3-p-tolyl-5,6-dihydro-4H-
[1,2,5]oxadiazine (4q). White crystalline solid; yield 50%;
mp 140–141 ꢂC; [Found: C, 77.89; H, 7.80; N, 9.14.
2.3.30. 1-Isopropyl-2-phenyl-4-p-tolyl-2,5-dihydro-1H-
imidazole 3-oxide (3t). White crystalline solid; yield 37%;
mp 133–134 ꢂC; [Found: C, 77.58; H, 7.50; N, 9.48.
C19H22N2O requires C, 77.52; H, 7.53; N, 9.52%]; nmax/cmꢀ1
(KBr): 1221 (N–O), 1547, 1595 (C]N); dH (200 MHz):
d 1.13–1.21 (m, 6H, 2ꢁCH3), 2.32 (s, 3H, CH3), 3.15–3.42
(m, 1H, –CH, isopropyl), 4.35 (dd, J¼14.2 and 4.2 Hz, 1H,
CH2), 4.62 (dd, J¼14.2 and 4.2 Hz, 1H, CH2), 5.75 (dd,
J¼3.7 and 4.1 Hz, 1H, methine), 6.65 (d, J¼8.5 Hz, 2H,
ArH), 6.99 (d, J¼8.5 Hz, 2H, ArH), 7.10–7.49 (m, 5H,
ArH); 13C NMR: 11.6, 20.6 (CH3), 21.4 (CH), 44.1 (CH2),
90.1 (methine), 127.8, 128.1, 129.5, 130.1, 130.9, 131.2,
134.1, 140.1, and 153.1; m/z: 294 (M+) and 278 (M+ꢀ16).
C20H24N2O requires C, 77.89; H, 7.84; N, 9.08%]; nmax
/
cmꢀ1 (KBr): 1625 (C]N); dH (200 MHz): d 0.94 (t,
J¼7.2 Hz, 3H, CH3), 1.38–1.62 (m, 4H, 2ꢁCH2), 2.35 (s,
3H, CH3), 2.73–2.81 (m, 2H, CH2), 3.62 (AB quartet,
J¼7.6 Hz, 2H, CH2, oxazine), 5.80 (s, 1H, methine), 6.58
(d, J¼8.2 Hz, 2H, ArH), 6.98 (d, J¼8.2 Hz, 2H, ArH),
7.07–7.42 (m, 5H, ArH); 13C NMR: 13.7, 20.2, 21.2, 30.2,
45.1, 52.0, 91.1, 121.1, 122.8, 123.9, 126.2, 128.9, 139.1,
141.4, 149.1, and 153.1; m/z: 308.42 (M+).
2.3.26. 1-Butyl-4-(4-nitro-phenyl)-2-phenyl-2,5-dihydro-
1H-imidazole 3-oxide (3r). White crystalline solid; yield
31%; mp 125–126 ꢂC; [Found: C, 67.29; H, 6.20; N,
12.35. C19H21N3O3 requires C, 67.24; H, 6.24; N,
12.38%]; nmax/cmꢀ1 (KBr): 1219 (N–O), 1549, 1600
(C]N); dH (200 MHz): d 0.92 (t, J¼7.4 Hz, 3H, CH3),
1.38–1.63 (m, 4H, 2ꢁCH2), 2.75–2.85 (m, 2H, CH2), 4.35
(dd, J¼14.7 and 3.6 Hz, 1H, CH2), 4.75 (dd, J¼14.7 and
4.2 Hz, 1H, CH2), 5.75 (dd, J¼3.2 and 4.5 Hz, 1H, methine),
7.41–7.68 (m, 5H, ArH), 7.91 (d, J¼8.8 Hz, 2H, ArH), 8.32
(d, J¼8.7 Hz, 2H, ArH); 13C NMR: 13.5, 21.2, 28.9, 45.3,
51.4, 93.8, 122.7, 123.5, 127.1, 129.4, 129.9, 139.4, 143.1,
150.2, and 153.2; m/z: 339 (M+) and 326 (M+ꢀ16).
2.3.31. 5-Isopropyl-6-phenyl-3-p-tolyl-5,6-dihydro-4H-
[1,2,5]oxadiazine (4t). White crystalline solid; yield 48%;
mp 105–106 ꢂC; [Found: C, 77.59; H, 7.48; N, 9.58.
C19H22N2O requires C, 77.52; H, 7.53; N, 9.52%]; nmax
/
cmꢀ1 (KBr): 1620 (C]N); dH (200 MHz): d 1.15–1.22
(m, 6H, 2ꢁCH3), 2.32 (s, 3H, CH3), 3.25–3.50 (m, 1H,
–CH, isopropyl), 3.95 (s, 2H, oxazine CH2), 5.98 (s, 1H,
methine), 6.94 (d, J¼8.6 Hz, 2H, ArH), 7.02 (d, J¼8.6 Hz,
2H, ArH), 7.12–7.45 (m, 5H, ArH); 13C NMR: 11.4, 20.5
(CH3), 22.0 (CH), 45.4 (CH2), 93.1 (methine), 128.1,
129.2, 129.9, 131.1, 132.8, 133.2, 134.1, 137.4, and 152.5;
m/z: 294 (M+) and 278 (M+ꢀ16).
2.3.27. 5-Butyl-3-(4-nitro-phenyl)-6-phenyl-5,6-dihydro-
4H-[1,2,5]oxadiazine (4r). White crystalline solid; yield
53%; mp 105–106 ꢂC; [Found: C, 67.29; H, 6.20; N,
12.35. C19H21N3O3 requires C, 67.24; H, 6.24; N,
12.38%]; nmax/cmꢀ1 (KBr): 1620 (C]N); dH (200 MHz):
2.3.32. 1-Isopropyl-4-(4-nitro-phenyl)-2-phenyl-2,5-di-
hydro-1H-imidazole 3-oxide (3u). White crystalline solid;
yield 31%; mp 111–112 ꢂC; [Found: C, 66.51; H, 5.85; N,
12.94. C18H19N3O3 requires C, 66.45; H, 5.89; N, 12.91%];

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A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
nmax/cmꢀ1 (KBr): 1219 (N–O), 1545, 1596 (C]N); dH
(200 MHz): d 1.15–1.22 (m, 6H, 2ꢁCH3), 3.21–3.48 (m,
1H, –CH, isopropyl), 4.22 (dd, J¼14.7 and 3.6 Hz, 1H,
CH2), 4.68 (dd, J¼14.7 and 4.2 Hz, 1H, CH2), 5.72 (dd,
J¼3.6 and 4.2 Hz, 1H, methine), 7.35–7.61 (m, 5H, ArH),
7.82 (d, J¼8.7 Hz, 2H, ArH), 8.27 (d, J¼8.7 Hz, 2H, ArH);
13C NMR: 11.4, 21.3 (CH, isopropyl), 43.5 (CH2), 90.1
(methine), 127.2, 127.9, 128.4, 129.1, 130.5, 130.7, 132.4,
133.9, and 154.2; m/z: 325 (M+) and 309 (M+ꢀ16).
131.1, 133.4, 134.2, 137.3, 147.4, 152.1, and 152.9; m/z:
332 (M+) and 316 (M+ꢀ16).
2.3.37. 5-Furan-2-ylmethyl-6-phenyl-3-p-tolyl-5,6-di-
hydro-4H-[1,2,5]oxadiazine (4w). White crystalline solid;
yield 54%; mp 130–131 ꢂC. [Found: C, 75.92; H, 6.10; N,
8.45. C21H20N2O2 requires C, 75.88; H, 6.06; N, 8.43%];
nmax/cmꢀ1 (KBr): 1621 (C]N); dH (200 MHz): d 2.35 (s,
3H, CH3), 3.63 (s, 2H, CH2), 3.83 (d, J¼14.7 Hz, 1H, furyl),
3.94 (d, J¼14.7 Hz, 1H, furyl), 5.78 (s, 1H, methine), 6.27–
6.33 (m, 2H, Hb and Hc), 6.99–7.02 (d, J¼8.2 Hz, 2H, ArH),
7.13–7.80 (m, 8H, 7ArH and 1H, Ha); 13C NMR: 20.9,
53.7, 56.4, 94.4, 111.8, 118.3, 120.8, 121.9, 122.8, 124.6,
127.0, 129.2, 130.1, 133.2, 147.5, 151.4, and 153.0; m/z:
332 (M+).
2.3.33. 5-Isopropyl-3-(4-nitro-phenyl)-6-phenyl-5,6-di-
hydro-4H-[1,2,5]oxadiazine (4u). White crystalline solid;
yield 52%; mp 98–99 ꢂC; [Found: C, 66.50; H, 5.85; N,
12.98. C18H19N3O3 requires C, 66.45; H, 5.89; N, 12.91%];
nmax/cmꢀ1 (KBr): 1621 (C]N); dH (200 MHz): d 1.17–1.25
(m, 6H, 2ꢁCH3), 3.25–3.51 (m, 1H, –CH, isopropyl), 3.61
(s, 2H, –CH2, oxazine), 5.91 (s, 1H, methine), 7.29–7.55
(m, 5H, ArH), 7.73 (d, J¼8.7 Hz, 2H, ArH), 8.19 (d, J¼
8.7 Hz, 2H, ArH); 13C NMR: 11.2, 21.2, 42.4, 94.8, 127.5,
128.2, 128.7, 128.9, 130.1, 130.5, 132.1, 134.2, and 153.5;
m/z: 325 (M+); Anal. Calcd for: C, 66.45; H, 5.89; N, 12.91.
2.3.38. 1-Furan-3-ylmethyl-4-(4-nitro-phenyl)-2-phenyl-
2,5-dihydro-1H-imidazole 3-oxide (3x). Bright yellow
crystalline solid; yield 30%; mp 155–156 ꢂC. [Found: C,
66.16; H, 4.76; N, 11.59. C20H17N3O4 requires C, 66.11;
H, 4.72; N, 11.56%]; nmax/cmꢀ1 (KBr): 1220 (N–O), 1551,
1589 (C]N); dH (200 MHz): d 3.84 (d, J¼14.8 Hz, 1H,
furyl CH2), 3.98 (d, J¼14.8 Hz, 1H, furyl), 4.26 (dd,
J¼14.1 and 4.5 Hz, 1H, –CH2–), 4.56 (dd, J¼14.1 and
3.7 Hz, 1H, –CH2–), 5.61 (dd, J¼4.4 and 3.5 Hz, 1H,
methine), 6.27–6.36 (m, 2H, Hb and Hc), 7.27–7.62 (m,
6H, 5ArH and Ha), 8.26 (d, J¼8.9 Hz, 2H, ArH), 8.39 (d,
J¼8.9 Hz, 2H, ArH); 13C NMR: 53.9 (–CH2–), 56.3
(–CH2), 94.6 (methine), 112.1, 121.2, 123.6, 126.9, 127.7,
128.6, 130.0, 133.3, 133.6, 136.5, 147.6, 151.8, and 152.9;
m/z: 363 (M+) and 347 (M+ꢀ16).
2.3.34. 1-Furan-2-ylmethyl-2,4-diphenyl-2,5-dihydro-
1H-imidazole 3-oxide (3v). White crystalline solid; yield
34%; mp 138–139 ꢂC. [Found: C, 66.50; H, 5.85; N,
12.98. C18H19N3O3 requires C, 66.45; H, 5.89; N,
12.91%]; nmax/cmꢀ1 (KBr): 1219 (N–O), 1545, 1597
(C]N); dH (200 MHz): d 3.81 (d, J¼14.6 Hz, 1H, furyl),
3.92 (d, J¼14.6 Hz, 1H, furyl), 4.2 (dd, J¼14.2 and
4.5 Hz, 1H, –CH2–), 4.56 (dd, J¼14.2 and 3.3 Hz, 1H,
–CH2–), 5.62 (dd, J¼4.5 and 3.3 Hz, 1H, methine), 6.23–
6.32 (m, 2H, Hb and Hc), 6.42–7.53 (m, 11H, 10ArH and
1H, Ha); 13C NMR: 54.2, 56.5, 94.5 (methine), 111.8,
119.3, 122.4, 126.8, 127.5, 129.2, 132.6, 134.3, 137.5,
139.2, 148.2, 152.2, and 154.1; m/z: 318 (M+) and 302
(M+ꢀ16); Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70;
N, 8.80; Found: C, 75.50; H, 5.76; N, 8.82.
2.3.39. 5-Furan-2-ylmethyl-3-(4-nitro-phenyl)-6-phenyl-
5,6-dihydro-4H-[1,2,5]oxadiazine (4x). Yellow crystalline
solid; yield 50%; mp 126–127 ꢂC. [Found: C, 66.15; H,
4.76; N, 11.58. C20H17N3O4 requires C, 66.11; H, 4.72; N,
11.56%]; nmax/cmꢀ1 (KBr): 1625 (C]N); dH (200 MHz):
d 3.65 (s, 2H, CH2), 3.82 (d, J¼14.6 Hz, 1H, furyl), 3.93
(d, J¼14.6 Hz, 1H, furyl), 5.77 (s, 1H, methine), 6.28–
6.33 (m, 2H, Hb and Hc), 7.26–7.56 (m, 6H, 5ArH and 1H,
Ha), 7.74 (d, J¼8.8 Hz, 2H, ArH), 8.23 (d, J¼8.8 Hz, 2H,
ArH); 13C NMR: 53.8 (–CH2–), 56.3, 94.5 (methine),
111.9, 118.2, 121.3, 122.3, 123.7, 125.9, 127.8, 129.1,
130.5, 133.4, 147.5, 151.5, and 153.1; m/z: 363 (M+).
2.3.35. 5-Furan-2-ylmethyl-3,6-diphenyl-5,6-dihydro-
4H-[1,2,5]oxadiazine (4v). White crystalline solid; yield
49%; mp 121–122 ꢂC. [Found: C, 75.51; H, 5.78; N, 8.85.
C20H18N2O2 requires C, 75.45; H, 5.70; N, 8.80%]; nmax
/
cmꢀ1 (KBr): 1625 (C]N); dH (200 MHz): d 3.62 (s, 2H,
CH2), 3.82 (d, J¼14.7 Hz, 1H, furyl), 3.91 (d, J¼14.7 Hz,
1H, furyl), 5.78 (s, 1H, methine), 6.26–6.33 (m, 2H, Hb
and Hc), 6.78–7.32 (m, 5H, 4ArH and 1H, Ha), 7.34–7.48
(m, 6H, ArH); 13C NMR: 53.8, 56.5, 94.5, 112.0, 117.9,
120.8, 121.3, 125.7, 126.5, 127.3, 130.5, 132.6, 135.4,
146.9, 151.2, and 153.1; m/z: 318 (M+).
2.4. Reactions of 2-methyl-1-aryl-isothioureas 7a–c and
N-aryl-secondary amine-carboxamidines 7d–f with
a-nitrosoalkenes
A solution of carboxamidines or isothioureas 7 (4 mmol)
and a-bromooxime 2 (4.2 mmol) in dry CH2Cl2 (20 ml)
was stirred at rt in the presence of sodium bicarbonate for
2–3 h. Work up identical with that employed for the nitrone
3 gave the crude products 8, which were purified by column
chromatography on silica gel (EtOAc–hexane :: 1:9) to yield
the corresponding imidazoles 8 (75–85%).
2.3.36. 1-Furan-2-ylmethyl-2-phenyl-4-p-tolyl-2,5-di-
hydro-1H-imidazole 3-oxide (3w). White crystalline solid;
yield 31%; mp 145–146 ꢂC. [Found: C, 75.93; H, 6.12; N,
8.45. C21H20N2O2 requires C, 75.88; H, 6.06; N, 8.43%];
nmax/cmꢀ1 (KBr): 1219 (N–O), 1550, 1595 (C]N); dH
(200 MHz): d 2.39 (s, 3H, CH3), 3.83 (d, J¼14.7 Hz, 1H,
furyl), 3.94 (d, J¼14.7 Hz, 1H, furyl), 4.24 (dd, J¼14.1
and 4.4 Hz, 1H, –CH2–), 4.54 (dd, J¼14.1 and 3.5 Hz, 1H,
–CH2–), 5.60 (dd, J¼4.4 and 3.5 Hz, 1H, methine), 6.29–
6.31 (m, 2H, Hb and Hc), 6.99–7.01 (d, J¼8.4 Hz, 2H,
ArH), 7.03–7.06 (d, J¼8.4 Hz, 2H, ArH), 7.17–7.45 (m,
6H, 5ArH and 1H, Ha); 13C NMR: 21.5 (CH3), 54.0, 56.4,
94.6 (methine), 112.4, 120.9, 124.0, 127.0, 128.1, 128.8,
2.4.1. 2-Methylsulfanyl-1-phenyl-4-p-tolyl-1H-imidazole
(8a). Mp 145–146 ꢂC; yield 78%; [Found: C, 72.85; H,
5.73; N, 10.01. C17H16N2S requires C, 72.82; H, 5.75; N,
9.99%]; nmax/cmꢀ1 (KBr): 1592 (C]N); dH (200 MHz):
d 2.35 (s, 3H, CH3), 2.47 (s, 3H, SCH3), 6.51 (d,
J¼8.2 Hz, 2H, ArH), 7.21 (d, J¼8.2 Hz, 2H, ArH), 7.45

A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
5485
(s, 1H, Ha), 7.47–7.52 (m, 5H, ArH); dC (200 MHz): d 18.9
References and notes
(SCH3); 20.9 (CH3); 121.0, 123.1, 125.2, 126.9, 128.0,
129.4, 129.7, 133.5, 136.7, and 137.7; m/z: 280.39 (M+),
280.10 (100%), 281.11 (19.1%), and 282.10 (4.6%).
1. For reviews on nitrosodienophiles, see: (a) Boger, D. L.
Tetrahedron 1983, 39, 2869; (b) Weinreb, S. M. Comprehensive
Organic Synthesis; Trost, B. M., Flemming, I., Paquette, L. A.,
Eds.; Pergamon: New York, NY, 1991; p 401; (c) Waldman, H.
Synthesis 1994, 535; (d) Waldman, H. Organic Synthesis High-
lights II; VCH: New York, NY, 1995; 37; (e) Zuman, P.; Shah,
B. Chem. Rev. 1994, 94, 1621.
2. For reviews on acylnitroso species, see: (a) Kirby, G. W. Chem.
Soc. Rev. 1977, 1; (b) Vogt, P. F.; Miller, M. J. Tetrahedron
1998, 54, 1317.
3. (a) Gilchrist, T. L. Chem. Soc. Rev. 1983, 12, 53; (b) Lyapkalo,
I. M.; Loffe, S. L. Russ. Chem. Rev. 1998, 67, 467; (c) Crystal,
E. J. T.; Gilchrist, T. L.; Stretch, W. J. Chem. Res., Synop. 1987,
180; J. Chem. Res., Miniprint 1987, 1563 and the references
cited therein; (d) Zimmer, R.; Reissig, H. U. Angew. Chem.,
Int. Ed. Engl. 1988, 27, 1518; (e) Faragher, R.; Gilchrist,
T. L. J. Chem. Soc., Chem. Commun. 1976, 581; (f) Faragher,
R.; Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1979, 258;
(g) Faragher, R.; Gilchrist, T. L. J. Chem. Soc., Perkin Trans.
1 1979, 249; (h) Gilchrist, T. L.; Lingham, D. A.; Roberts,
T. G. J. Chem. Soc., Chem. Commun. 1979, 1089; (i) Gilchrist,
T. L.; Iskander, G. M.; Yagoub, A. K. J. Chem. Soc., Chem.
Commun. 1981, 696.
4. Sharma, A. K.; Mahajan, M. P. Heterocycles 1995, 40, 787.
5. (a) Lai, E. C. K.; Mackay, D.; Taylor, N. J.; Watson, K. N.
J. Chem. Soc., Perkin Trans. 1 1497, 1990; (b) Mackay, D.;
Watson, K. N. J. Chem. Soc., Chem. Commun. 1982, 777; (c)
Mackay, D.; Papadopaelos, D.; Taylor, N. J. J. Chem. Commun.
1992, 325; (d) Mackay, D.; Mctyre, D. D.; Wigle, I. D. J. Chem.
Soc., Perkin Trans. 1 1989, 1999.
6. (a) Sharma, A. K.; Mazumdar, S. N.; Mahajan, M. P. J. Chem.
Soc., Perkin Trans. 1 1997, 3065; (b) Sharma, A. K.; Hundal,
G.; Obrai, S.; Mahajan, M. P. J. Chem. Soc., Perkin Trans. 1
1999, 615; (c) Sharma, A. K.; Mazumdar, S. N.; Mahajan,
M. P. Tetrahedron Lett. 1993, 34, 7961; (d) Bravo, P.;
Gaudiano, G.; Panti, P. P.; Umani-Ronchi, A. Tetrahedron
1970, 26, 1315.
7. (a) Tahdi, A.; Lafquih-Titouani, S.; Soufiaoui, M.; Komiha, N.;
Kabbaj, O. K.; Hegazi, S.; Mazzah, A.; Eddaif, A. Tetrahedron
2002, 58, 1507; (b) Komiha, N.; Kabbaj, O. K.; Lafquih-
Tiouani, S. Internet Electron. J. Mol. Des. 2004, 1538 ISSN;
(c) Sperling, D.; Mehlhorn, A.; Reibig, H. U.; Fabian. J. Liebig
Ann. 1996, 1615.
2.4.2. 4-[4-(4-Nitro-phenyl)-1-phenyl-1H-imidazol-2-yl]-
morpholine (8e). Mp 165–166 ꢂC; yield 81%; [Found: C,
65.14; H, 5.20; N, 15.97. C19H18N4O3 requires C, 65.13;
H, 5.18; N, 15.99%]; nmax/cmꢀ1 (KBr): 1595 (C]N); dH
(200 MHz): d 2.92 (m, 4H, –CH2–N–CH2–), 3.67 (m, 4H,
–CH2–O–CH2–), 7.19–7.32 (m, 6H, 5 aromatic+1 olefenic),
8.24 (d, 2H, J¼8.0 Hz, arom), 8.40 (d, 2H, J¼8.0 Hz, arom);
dC (200 MHz): d 58.9 (–CH2–N–CH2–), 71.4 (–CH2–O–
CH2–), 121.0, 123.2, 124.1, 125.0, 127.9, 128.0, 129.4,
136.7, 137.0, 142.6, and 148.4; m/z: 350.37 (M+), 350.14
(100%), 351.14 (21.5%), and 352.14 (3.1%).
2.4.3. 2-Pyrrolidin-1-yl-1, 4-di-p-tolyl-1H-imidazole (8f).
Mp 132–133 ꢂC; yield 85%; [Found: C, 79.49; H, 7.31; N,
13.21. C21H23N3 requires C, 79.46; H, 7.30; N, 13.24%];
nmax/cmꢀ1 (KBr): 1601 (C]N); dH (200 MHz): d 1.59 (m,
4H, –CH2–CH2–), 2.32 (s, 3H, CH3), 2.81 (m, 4H, –CH2–
N–CH2–), 6.79 (d, J¼8.0 Hz, 2H, ArH), 7.05 (m, 3H, 2 aro-
matic+1 olefenic), 7.12 (d, 2H, J¼8.0 Hz, arom), 7.36 (d,
2H, J¼8.0 Hz, arom); dC (200 MHz): d 20.5 (CH3), 20.9
(CH3), 25.1 (–CH2–CH2–), 47.7 (–CH2–N–CH2–), 120.9,
123.0, 125.2, 126.9, 129.7, 130.1, 133.5, 133.7, 137.0,
137.2, and 137.7; m/z: 317.43 (M+), 317.19 (100%),
318.19 (24.5%), and 319.20 (2.7%).
2.5. Reactions of N-phenyl-secondaryamino-1-carboximi-
dothioic acid allyl ester 15a–d and 2-allyl-1,1-dimethyl-
3-phenyl-isothiourea 15e–f with a-nitrosoalkenes
A solution of S-allylated imines 15 (4 mmol) and a-bromo-
oxime 2 (4.2 mmol) in dry CH2Cl2 (20 ml) was stirred at rt in
the presence of sodium bicarbonate for 2–3 h. Work up iden-
tical with that employed for the nitrones 3 and 8 gave the
crude products, which were purified by column chromato-
graphy on silica gel (EtOAc–hexane:: 1:10) to yield the cor-
responding products 16 (70–80%).
2.5.1. 1,4-Diphenyl-2-pyrrolidin-1-yl-1H-imidazole 3-
oxide (16a). Mp 142–143 ꢂC; yield 77%; [Found: C, 74.76;
H, 6.20; N, 13.75. C19H19N3O requires C, 74.73; H, 6.27;
N, 13.76%]; nmax/cmꢀ1 (KBr): 1223 (N–O), 1583, 1596
(C]N); dH (200 MHz): d 1.79 (m, 4H, –CH2–CH2–), 3.30
(m, 4H, –CH2–N–CH2–), 6.88 (m, 1H, olefenic), 7.08–7.32
(m, 10H, ArH); dC (200 MHz): d 22.6, 45.7, 69.2, 119.6,
122.7, 125.2, 126.5, 127.1, 128.7, 130.2, 132.5, 139.1, and
154.2; m/z: 305 (M+).
8. Marwaha, A.; Bharatam, P. V.; Mahajan, M. P. Tetrahedron
Lett. 2005, 46, 8253.
9. Delpierre, G. R.; Lamchen, M. Q. Rev. Chem. Soc. 1965, 19,
329.
10. Nakanishi, S.; Nantaku, J.; Otsuji, Y. Chem. Lett. 1983, 341.
11. (a) Davis, D. E.; Gilchrist, T. L.; Roberts, T. G. J. Chem. Soc.,
Perkin Trans. 1 1983, 1275; (b) Smith, J. H.; Heidema, J. H.;
Kaiser, E. T. J. Am. Chem. Soc. 1972, 94, 9276.
12. Hehre, W. J.; Radom, L.; Schleyer, P. V. R.; Pople, J. A. Ab ini-
tio Molecular Orbital Theory; Wiley: New York, NY, 1986.
13. Frisch, M. J.; Trucks, T.; Peterson, G. A.; Montogomery, J. A.;
Raghavachari, K.; Al-Laham, M. A.; Zakrzawski, V. G.;
Poresman, J. A.; Oritz, J. V.; Andres, J. L.; Replogle, E. S.;
Gompetrs, R.; Martin, R. L.; Fox, D. J.; Binkley, J. S.; Defrees,
D. L.; Baker, J.; Stewart, J. P.; Head-Gordon, M.; Gonzalez, C.;
Pople, J. A. GAUSSIAN 94, Revision B.2; Guassian: Pittsburg,
PA, 1995.
2.5.2. 1-(3-Oxy-1,4-diphenyl-1H-imidazol-2-yl)-piperi-
dine (16b). Mp 153–154 ꢂC; yield 80%; [Found: C, 75.24;
H, 6.62; N, 13.17. C20H21N3O requires C, 75.21; H, 6.63;
N, 13.16%]; nmax/cmꢀ1 (KBr): 1219 (N–O), 1599, 1652
(C]N); dH (200 MHz): d 1.58 (m, 6H, –CH2–CH2–CH2–),
2.83 (m, 2H, –N–CH2–), 3.42 (m, 2H, –N–CH2–), 6.49 (m,
1H, olefenic), 6.83–7.45 (m, 10H, ArH); dC (200 MHz):
d 25.2 (–CH2–CH2–), 26.2 (CH2), 55.1 (–CH2–N–CH2–),
70.1, 119.8, 123.2, 125.9, 126.2, 127.5, 128.5, 130.0,
140.2, and 153.2; m/z: 319 (M+).

5486
A. Marwaha et al. / Tetrahedron 62 (2006) 5474–5486
14. (a) Tranmer, G. K.; Tam, W. J. Org. Chem. 2001, 66, 5113; (b)
Goti, A.; Cicchi, S.; Cordero, F. M.; Fedi, V.; Brandi, A.
Molecules 1999, 4, 1; (c) Murahashi, S. I.; Mitsui, H.; Shiota,
T.; Tsuda, T.; Watanabe, S. J. Org. Chem. 1990, 55, 1736 and
references cited therein; (d) Dagoneau, C.; Tomassini, A.;
Denis, J. N. Synthesis 2001, 150.
MgSO4 (7.5 mmol) at rt for 3–4 h. The reaction mixture was
filtered and the residue was washed with CH2Cl2 (10 ml).
The combined was then washed with water (3ꢁ50 ml) and
dried over anhydrous sodium sulfate. The solvent was removed
under reduced pressure and the crude product thus obtained
was recrystallized with EtOAc–hexane :: 1:9); (b) McNeil
Lab., G.B. 1573532, 1976; D.E. 2711757; Chem. Abstr. EN
88, 37603; (c) Korter, H.; Scholl, R. Ber. 1901, 34, 1901.
15. (a) Preparation of Schiff’s bases: A mixture of primary amine
(5 mmol) in CH2Cl2 (30 ml) was stirred in the presence of