Tandem [2+2] cycloaddition and Cope rearrangement in reactions of cross-conjugated azatrienes with conjugated ketenes: a facile single step synthesis of novel azocinone derivatives

Article abstract of DOI:10.1016/j.tet.2006.09.007

A facile single step synthesis of novel azocinone derivatives involving tandem [2+2] cycloaddition and Cope rearrangement in the reactions of cross-conjugated azatrienes with vinyl/isopropenyl ketenes supported by theoretical calculations is reported.

Full text of DOI:10.1016/j.tet.2006.09.007

Tetrahedron 62 (2006) 11267–11273
Tandem [2D2] cycloaddition and Cope rearrangement
in reactions of cross-conjugated azatrienes with
conjugated ketenes: a facile single step synthesis
of novel azocinone derivatives
*
Parvesh Singh, Gaurav Bhargava and Mohinder P. Mahajan
Department of Applied Chemistry, Guru Nanak Dev University, Amritsar-143005, Punjab, India
Received 20 June 2006; revised 17 August 2006; accepted 1 September 2006
Available online 5 October 2006
Abstract—A facile single step synthesis of novel azocinone derivatives involving tandem [2+2] cycloaddition and Cope rearrangement in the
reactions of cross-conjugated azatrienes with vinyl/isopropenyl ketenes supported by theoretical calculations is reported.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
reaction conditions and the non-availability of pure starting
materials. Our continued interest in the utilization of aza-
dienes in cycloaddition reactions,2 coupled with the syn-
thetic potential of cross-conjugated azatrienes prompted us
to explore the isolation of azatrienes as stable synthons prior
to their utilization in hetero DA reactions.
Nitrogen heterocycles are among the most useful and their
utility has been widely demonstrated in the chemistry of nat-
ural products, in material sciences, and in pharmaceutical
chemistry.1 Their synthesis has attracted considerable atten-
tion due to their large importance as building blocks for
many therapeutically useful materials, as well as for the
wide range of potential biological activity of both synthetic
and naturally occurring derivatives. The hetero Diels–Alder
reactions of azadienes are one of the most versatile routes for
the synthesis of such nitrogen heterocycles. Extensive efforts
have been carried out toward the Diels–Alder cycloadditions
involving azadienes containing one or more nitrogen atoms
and the rapid developments in this area have been reviewed.1
A large variety of nitrogen heterocycles have been synthe-
sized in our laboratory by the cycloaddition reactions of aza-
dienes with a number of dienophiles.2
The procedure for the synthesis of stable cross-conjugated
azatrienes involves the treatment of the corresponding
ketone 1 (10 mmol) with aromatic amine 2 (15 mmol) in
the presence of titanium tetrachloride (10 mmol) and tri-
ethylamine (22 mmol) in dry toluene at 0 ꢀC (Scheme 1).
After completion, the reaction mixture was passed through
a silica column and distillation of the solvent under reduced
pressure yielded solid compounds in very good yields (71–
88%).
Saito et al. examined the reactions of azatriene 3c with di-
substituted ketenes and obtained [2+2] cycloadducts, which
upon heating in toluene underwent [1,3] sigmatropic rear-
rangement to yield pyridone derivatives.3b Recently, Alcaide
and co-workers have reported that the reactions of 1-aza-
buta-1,3-dienes with vinyl/isopropenyl ketenes leading to
the initial formation of cis-3,4-divinyl-b-lactams as [2+2]
adducts, which upon thermolysis in refluxing toluene under-
went [3,3] sigmatropic shift to yield azocinone derivatives.5
However, the methodology used suffers several disadvan-
tages, for example, 3,4-divinyl-b-lactams, used for these
transformations, were prepared following a multiplet strat-
egy with natural loss of yields. Also, despite being a novel
synthetic route for few azocinones, the scope of this reaction
Recently, Saito and co-workers3 have reported the diene
transmissive hetero Diels–Alder (DTHDA) reactions of
some in situ generated cross-conjugated azatrienes, provid-
ing a synthetic access to ring fused heterocyclic frameworks.
However, despite being excellent synthons, their initial
[4+2] cycloaddition reaction has been restricted to a few
reactive heterocummulenes. The lack of extensive efforts
in this area may be due to their reported sensitivity to varying
Keywords: Azatrienes; Ketenes; Cycloadditions; Cope rearrangement.
* Corresponding author. Tel.: +91 183 2258802/09x3320; fax: +91 183
2258819/20; e-mail: mahajanmohinderp@yahoo.co.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.007

11268
P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
Ar
N
O
, (C2H5)3N:
TiCl4
Ar-NH2
+
,
Toluene 0 °C
R
R
R
R
2
3
1
3a. R = OCH3, Ar = p-methoxyphenyl (79%)
3b. R = OCH3, Ar = p-tolyl (82%)
3c. R = OCH3, Ar = phenyl (88%)
3d. R = H, Ar = p-methoxyphenyl (84%)
R = OCH3, H, Cl
Ar = p-methoxyphenyl, p-tolyl, phenyl
3e. R = H, Ar = p-tolyl (87%)
3f. R = H, Ar = phenyl (83%)
3g. R = Cl, Ar = p-methoxyphenyl (76%)
3h. R = Cl, Ar = phenyl (81%)
3i. R = Cl, Ar = p-tolyl (71%)
Scheme 1.
was limited to only few possible structural variants at N of
1-azabuta-1,3-diene.
cycloadducts, 3,4,4-trisubstituted-2-azetidinones 4, as tran-
sient intermediates. The comparison of tlc of the crude reac-
tion mixture with that of the pure product clearly ruled out
any possibility of the observed Cope rearrangement taking
place during processes such as recrystallization, work up,
etc.
In order to explore their scope and synthetic potential, we
have examined the reactions of the isolated azatrienes 3
with conjugated ketenes viz. vinyl/isopropenyl ketenes,
which themselves are known to participate either as 2p or
4p component in [2+2] and [4+2] cycloaddition reactions,4
generated in situ from the corresponding acid chlorides in
the presence of triethylamine in dry dichloromethane at
room temperature. Interestingly, these reactions resulted in
a facile single step synthesis of novel azocinone derivatives
in excellent yields (72–89%), instead of the expected trialkyl
3,4,4-azitidinin-2-ones.
The mechanism proposed above was further corroborated by
the energy minimization calculations performed at AM1
level using MOPAC program.6 The calculations reveal that
the product 5 is more stable than the initial [2+2] cyclo-
adduct 4 by 28.9 kcal molꢁ1 (Scheme 2).
The energy minimization calculations for 3,4,4-trisubsti-
tuted-2-azetidinones 4 indicate an energy of 130.8 kcal
The formation of azocinones 5 in these reactions is probably
the result of initial [2+2] cycloadditions and highly efficient
[3,3] sigmatropic rearrangements of the so formed [2+2]
molꢁ1 with apical distance (C12–C17) of 3.54 A and dihedral
˚
angles ꢁ89ꢀ (C14–C2–C6–C12) and ꢁ15ꢀ (C2–C14–C15–C17)
(Fig. 1). On the other hand, the energy minimization
R
Ar
Ar
2
O
N
O
N
CH3
R'
R' = CH3, H
1
1
(C H ) N:
CH2Cl2,
2
5 3
+
R'
Cl
2
stirring, rt
R
R
3
3
3
a. R = OCH3, Ar = p-methoxyphenyl
4
b. R = OCH3, Ar = p-tolyl
c. R = OCH3, Ar = phenyl
d. R = H, Ar = p-methoxyphenyl
e. R = H, Ar = p-tolyl
R
[3,3] shift
f. R = H, Ar = phenyl
Ar
H
O
N
H
R
H
H
R'
H
H
H
R
5
R'
Ar
Yield(%)
No.
5a.
R
CH3
85
82
81
88
89
83
72
78
86
80
77
76
p-methoxyphenyl
OCH3
5b.
5c.
5d.
5e.
5f.
p-methoxyphenyl
p-tolyl
H
OCH3
OCH3
OCH3
OCH3
OCH3
H
CH3
H
p-tolyl
phenyl
CH3
H
phenyl
CH3
5g.
p-methoxyphenyl
5h.
5i.
5j.
p-methoxyphenyl
p-tolyl
H
H
CH3
H
H
H
p-tolyl
5k.
5l.
CH3
H
H
H
phenyl
phenyl
Scheme 2.

P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
11269
130.8 kcal/mole
3.54 A°
4 with dihedral angles
-45° & -15°
(134.9 kcal/mole,
2.78 A°)
E
N
E
R
G
Y
4
C17
C15
C12
C6
C2
C14
28.9 kcal/mole
5 (101.9 kcal/mole)
Figure 1. Energy minimized structure of intermediate 4.
Reaction Coordinate
Figure 4. A probable graphical representation of reaction pathway.
calculations on 3,4-divinyl azetidinone earlier utilized in
thermolytic Cope rearrangement,5 have shown its ground
state energy as 80.6 kcal molꢁ1 with apical distance of
The methodology has been generalized for the synthesis of
other azocinone derivatives 5 (c–l) in the reactions of cross-
conjugated azatrienes (3b–3f) with conjugated ketenes
without even traces of corresponding [2+2] cycloadducts.
Since, the synthesis of eight- and nine-membered rings is
comparatively difficult due to their unfavorable enthalpic
and entropic factors,7,8 an easy and convenient route for
the synthesis of such eight membered lactams has been
developed (Fig. 4).
6
˚
3.87 A (Figs. 2 and 3).
In line with the arguments advanced above, the reduction
in dihedral angle increases the energy of the system to
102.2 kcal molꢁ1, a difference of 21.6 kcal. The resultant
energy barrier of 21.6 kcal molꢁ1 is naturally more difficult
to attain than 4.1 kcal molꢁ1 required for conversion of 4 to
5. This is also in agreement with the harsh conditions
required for the earlier reported Cope rearrangement.5
In conclusion, an unprecedented single pot synthesis of
stable cross-conjugated azatrienes 3 (a–f) along with the tan-
dem [2+2] cycloaddition and highly facile [3,3] sigmatropic
rearrangement in their reactions with conjugated ketenes,
leading to facile synthesis of various functionalised azoci-
none derivatives, has been reported. Alcaide and co-workers
in their communication exploited just the azadienic system
having limited variants thus imposing structural limitations
on the reaction site and restraining the diversity of the formed
azocinone derivatives. Whereas the systems considered in
our manuscript widens the scope of this methodology, as
many structural variants present in the cross-conjugated
system acting as 1-azadiene opens up a channel to obtain
novel functionalized azocinones. The facile nature of the
observed [3,3] sigmatropic shift has been supported by the
theoretical studies.
O
R'
H
N
2
12
15
14
H
H
17
C12-C17 = 2.78A0
6
H
H
H
Figure 2. Most probable conformation of 4 for Cope rearrangement.
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 FT-spectrophotometer. 1H NMR spectra
were recorded in deuterochloroform with Bruker AC-E 200
(200 MHz) spectrometer using TMS as an internal standard.
Chemical shift values are expressed as parts per million
downfield from TMS and J values are in hertz. Splitting
patterns are indicated as s: singlet, d: doublet and br s: broad
singlet. 13C NMR spectra were also recorded on a Bruker
Figure 3. Energy minimized most probable conformer of [2+2] adduct 4
required for Cope rearrangement.

11270
P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
AC-E 200 (50.4 MHz) spectrometer in a deuterochloroform
using TMS as an internal standard. Mass spectra were
recorded on Shimadzu GCMS-QP-2000 mass spectro-
meter. Elemental analyses were performed on Heraus
CHN-O-Rapid Elemental Analyzer. Column chromato-
graphy was performed on a silica gel (60–120) mesh or
Harrison Research Chromatotron using 2 mm plates (Silica
gel PF254).
2.4.2. {3-(4-Methoxy-phenyl)-1-[2-(4-methoxy-phenyl)-
vinyl]-allylidene}-p-tolyl-amine (3b). Reddish yellow
solid, Yield: 82%; mp 148–149 ꢀC; Anal. Calcd for
C26H25NO2: C, 81.43; H, 6.57; N, 3.65. Found: C, 81.37;
H, 6.51; N, 3.59%. IR (KBr) nmax¼1602, 1510, 1463,
1
1033 cmꢁ1; H NMR (200 MHz, CDCl3, Me4Si): d¼2.35
(s, 3H, –CH3), 3.81 (s, 3H, –OCH3), 3.84 (s, 3H, –OCH3),
6.66 (d, J¼16.5 Hz, 1H, olefinic), 6.80–6.94 (m, 6H,
ArH), 7.12 (d, J¼15.9 Hz, 1H, olefinic), 7.15 (d,
J¼15.9 Hz, 1H, olefinic), 7.25–7.36 (m, 4H, ArH), 7.47
(d, J¼16.5 Hz, 1H, olefinic), 7.53 (d, J¼8.9 Hz, 2H, ArH)
ppm; 13C NMR (50.4 MHz, CDCl3, Me4Si): d¼20.9, 55.3,
55.4, 114.2, 114.4, 120.7, 121.2, 123.4, 124.0, 128.3,
129.1, 129.3, 129.7, 130.3, 133.1, 137.5, 148.3, 160.3,
160.5, and 163.2. m/z: 383 (M+).
2.2. Starting materials
Cross-conjugated ketones 1 were prepared according to the
reported procedure.9 Crotyl and 3,3-dimethylacryl chlorides
were prepared from their corresponding acids and thionyl
chloride. Thionyl chloride was distilled before use. Aro-
matic amines used were commercially available. Dichloro-
methane was dried over di-phosphorous pentoxide and
2.4.3. {3-(4-Methoxy-phenyl)-1-[2-(4-methoxy-phenyl)-
vinyl]-allylidene}-phenyl-amine (3c). Yellow solid, Yield:
88%; mp 155–156 ꢀC; Anal. Calcd for C25H23NO2: C,
81.27; H, 6.27; N, 3.79. Found: C, 81.35; H, 6.34; N,
˚
stored over molecular sieves (4 A).
2.3. General procedure for the preparation of cross-
conjugated azatrienes (3)
3.73%. IR (KBr): nmax¼1603, 1510, 1462, 1033 cmꢁ1
;
1H NMR (200 MHz, CDCl3, Me4Si): d¼3.83 (s, 6H,
2ꢂ–OCH3), 6.66 (d, J¼16.5 Hz, 1H, olefinic), 6.78–7.05
(m, 7H, ArH), 7.11 (d, J¼15.9 Hz, 1H, olefinic), 7.13 (d,
J¼15.9 Hz, 1H, olefinic), 7.21–7.33 (m, 4H, ArH), 7.49
(d, J¼16.5 Hz, 1H, olefinic), 7.55 (d, J¼8.9 Hz, 2H, ArH)
ppm; 13C NMR (50.4 MHz, CDCl3, Me4Si): d¼55.4,
114.1, 114.5, 120.2, 121.7, 122.6, 123.7, 125.6, 127.8,
128.5, 129.6, 130.2, 132.9, 136.8, 149.5, 159.9, 160.2, and
163.1. m/z: 369 (M+).
To the solution of 1 (10 mmol) and aryl amine 2 (15 mmol)
in toluene (30 mL) was added triethylamine (22 mmol) and
reaction mixture was stirred. After stirring for 5 min TiCl4
(10 mmol) was added to the reaction mixture dropwise by
keeping the reaction temperature at 0 ꢀC. After completion
(tlc), the reaction mixture was passed through a silica col-
umn and distillation of the solvent under reduced pressure
yielded solid compounds, which were recrystallized using
ethyl acetate–hexane mixture (1:5, v/v).
2.4.4. (4-Methoxy-phenyl)-(3-phenyl-1-styryl-allyl-
idene)-amine (3d). Yellow solid, Yield: 84%; mp 119–
120 ꢀC; Anal. Calcd for C24H21NO: C, 84.92; H, 6.24; N,
4.13. Found: C, 85.02; H, 6.29; N, 4.18%. IR (KBr):
2.4. General procedure for the reaction of azatrienes
with isopropenyl/vinyl ketenes
1
To a well-stirred solution of azatrienes 3 (10 mmol) and tri-
ethylamine (15 mmol) in dry methylene chloride (30 mL)
was added dropwise a solution of 3,3-dimethylacryl chlo-
ride/crotyl chloride in dry methylene chloride (30 mL)
over a period of 0.5 h at room temperature. After completion
of the reaction (tlc), the reaction mixture was first washed
with saturated sodium bicarbonate solution (2ꢂ25 mL)
and water (2ꢂ50 mL) and the organic layer was dried over
anhydrous sodium sulfate. Removal of solvent under
reduced pressure yielded the crude product, which was puri-
fied by silica gel column chromatography using a mixture
of ethyl acetate and hexane (1:10, v/v).
nmax¼1602, 1510, 1460, 1033 cmꢁ1; H NMR (200 MHz,
CDCl3, Me4Si): d¼3.83 (s, 3H, –OCH3), 6.70 (d,
J¼16.5 Hz, 1H, olefinic), 6.86–6.97 (m, 7H, ArH), 7.13
(d, J¼15.8 Hz, 1H, olefinic), 7.15 (d, J¼16.5 Hz, 1H,
olefinic), 7.29–7.38 (m, 5H, ArH), 7.41 (d, J¼15.8 Hz,
1H, olefinic), 7.56 (d, J¼8.7 Hz, 2H, ArH) ppm; 13C NMR
(50.4 MHz, CDCl3, Me4Si): d¼55.3, 113.9, 114.6, 121.6,
122.6, 124.7, 127.3, 128.4, 128.6, 128.9, 129.4, 137.2,
138.5, 145.9, 156.8, 160.1, 160.7, and 162.9. m/z: 339 (M+).
2.4.5. (3-Phenyl-1-styryl-allylidene)-p-tolyl-amine (3e).
Yellow solid, Yield: 87%; mp 107–108 ꢀC; Anal. Calcd for
C24H21N: C, 89.12; H, 6.54; N, 4.33. Found: C, 89.22; H,
6.47; N, 4.38%. IR (KBr): nmax¼1603, 1512, 1465,
2.4.1. (4-Methoxy-phenyl)-{3-(4-methoxy-phenyl)-1-
[2(4-methoxy-phenyl)-vinyl]-allylidene}-amine (3a).
Reddish yellow prismatic crystalline solid, Yield: 79%; mp
161–163 ꢀC; Anal. Calcd for C26H25NO3: C, 78.17; H,
6.31; N, 3.51. Found: C, 78.34; H, 6.42; N, 3.42%. IR
1
1033 cmꢁ1; H NMR (200 MHz, CDCl3, Me4Si): d¼2.37
(s, 3H, –CH3), 6.81 (d, J¼16.5 Hz, 1H, olefinic), 6.85 (d,
J¼8.4 Hz, 2H, ArH), 7.17 (d, J¼15.9 Hz, 1H, olefinic),
7.19–7.64 (m, 14H, 12ArH and 2 olefinic) ppm; 13C NMR
(50.4 MHz, CDCl3, Me4Si): d¼20.9, 121.1, 122.5, 126.3,
127.3, 127.5, 128.7, 128.8, 128.9, 129.2, 129.4, 133.5,
135.8, 136.2, 137.8, 138.1, 148.0, and 162.8. m/z: 323 (M+).
(KBr): nmax¼1602, 1510, 1463, 1033 cmꢁ1
;
1H NMR
(200 MHz, CDCl3, Me4Si): d¼3.82 (s, 6H, 2ꢂ–OCH3),
3.84 (s, 3H, –OCH3), 6.68 (d, J¼16.5 Hz, 1H, olefinic),
6.84–6.93 (m, 7H, 6ArH and 1H, olefinic), 7.10 (d,
J¼16.5 Hz, 1H, olefinic), 7.13 (d, J¼16.5 Hz, 1H, olefinic),
7.25–7.55 (m, 6H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼55.2 (–OCH3), 55.3 (–OCH3), 114.0, 114.1,
114.2, 120.7, 122.7, 124.2, 128.3, 128.6, 128.9, 129.1,
136.9, 137.3, 144.2, 156.3, 160.2, 160.4, and 163.0. m/z:
399 (M+).
2.4.6. Phenyl-(3-phenyl-1-styryl-allylidene)-amine (3f).
Reddish yellow solid, Yield: 83%; mp 79–80 ꢀC; Anal.
Calcd for C23H19N: C, 89.28; H, 6.19; N, 4.53. Found: C,
89.21; H, 6.25; N, 4.48%. IR (KBr): nmax¼1602, 1510,
1463, 1033 cmꢁ1 1H NMR (200 MHz, CDCl3, Me4Si):
;
d¼6.76 (d, J¼16.5 Hz, 1H, olefinic), 6.90–7.13 (m, 3H,

P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
11271
2ArH and 1 olefinic), 7.18 (d, J¼16.5 Hz, 1H, olefinic),
7.22–7.63 (m, 13H, ArH), 7.75 (d, J¼16.5 Hz, 1H, olefinic)
ppm; 13C NMR (50.4 MHz, CDCl3, Me4Si): d¼120.9,
122.3, 123.8, 125.9, 127.5, 128.3, 128.7, 128.9, 129.0,
130.4, 134.7, 135.7, 136.1, 138.0, 143.3, 150.7, and 162.9.
m/z: 309 (M+).
1H, olefinic), 5.99 (br s, 1H, olefinic), 6.34 (d, J¼16.2 Hz,
1H, olefinic), 6.42 (d, J¼16.2 Hz, 1H, olefinic), 6.74–6.94
(m, 6H, ArH), 7.15–7.35 (m, 6H, ArH) ppm; 13C NMR
(50.4 MHz, CDCl3, Me4Si): d¼26.1 (–CH3), 39.9 (–CH2),
42.6 (–CH), 55.2 (–OCH3), 55.3(–OCH3), 96.1, 113.9,
114.3, 120.1, 122.3, 126.4, 127.7, 127.9, 129.1, 130.7,
132.1, 132.3, 134.5, 138.7, 140.2, 157.6, 158.6, 159.4, and
168.5. m/z: 481 (M+).
2.4.7. {3-(4-Chloro-phenyl)-1-[2-(4-chloro-phenyl)-
vinyl]-allylidene}-(4-methoxy-phenyl)-amine (3g). Yel-
low crystalline solid, Yield: 76%; mp 110–111 ꢀC; Anal.
Calcd for C24H19Cl2NO: C, 70.60; H, 4.69; N, 3.43. Found:
C, 70.66; H, 4.62; N, 3.52%. IR (KBr): nmax¼1603, 1510,
2.4.11. 1,6-Bis-(4-methoxy-phenyl)-8-[2-(4-methoxy-
phenyl)-vinyl]-5,6-dihydro-1H-azocin-2-one (5b). Color-
less solid, Yield: 82%; mp 191–192 ꢀC; Anal. Calcd for
C30H29NO4: C, 77.06; H, 6.21; N, 3.00. Found: C, 77.13;
H, 6.13; N, 2.93%. IR (KBr): nmax¼1660, 1512, 1338,
1462, 1033 cmꢁ1 1H NMR (200 MHz, CDCl3, Me4Si):
;
d¼3.81 (s, 3H, –OCH3), 6.76 (d, J¼16.5 Hz, 1H, olefinic),
7.01 (d, J¼15.9 Hz, 1H, olefinic), 7.08 (d, J¼16.5 Hz, 1H,
olefinic), 7.19–7.31 (m, 4H, ArH), 7.36 (d, J¼8.9 Hz, 2H,
ArH), 7.37 (d, J¼8.9 Hz, 2H, ArH), 7.49 (d, J¼8.4 Hz,
2H, ArH), 7.52 (d, J¼8.4 Hz, 2H, ArH), 7.66 (d,
J¼15.9 Hz, 1H, olefinic) ppm; 13C NMR (50.4 MHz,
CDCl3, Me4Si): d¼55.4, 114.1, 120.8, 122.9, 124.7, 126.5,
127.6, 128.2, 128.7, 129.5, 130.1, 134.8, 135.6, 137.6,
137.8, 141.5, 152.6, and 161.1. m/z: 408 (M+).
1299, 1030 cmꢁ1 1H NMR (200 MHz, CDCl3, Me4Si):
;
d¼2.41–2.47 (m, 1H, –CH2), 2.76–2.82 (m, 1H, –CH2),
3.81 (s, 6H, 2ꢂ–OCH3), 3.83 (s, 3H, –OCH3), 4.13–4.18
(m, 1H, –CH), 5.93 (br s, 1H, olefinic), 5.99 (d,
J¼10.1 Hz, 1H, olefinic), 6.02 (br s, 1H, olefinic), 6.43
(br s, 2H, olefinic), 6.71–6.89 (m, 6H, ArH), 7.13–7.38 (m,
6H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3, Me4Si):
d¼37.5, 40.8, 55.2, 55.5, 96.2, 114.1, 114.5, 120.5, 122.3,
123.7, 126.4, 127.7, 129.8, 131.4, 132.2, 133.8, 135.4,
137.6, 138.9, 141.2, 142.5, 157.4, and 168.5. m/z: 467 (M+).
2.4.8. {3-(4-Chloro-phenyl)-1-[2-(4-chloro-phenyl)-
vinyl]-allylidene}-p-tolyl-amine (3h). Yellow solid, Yield:
81%; mp 124–125 ꢀC; Anal. Calcd for C24H19Cl2N: C,
73.47; H, 4.88; N, 3.57. Found: C, 73.51; H, 4.83; N,
2.4.12. 6-(4-Methoxy-phenyl)-8-[2-(4-methoxy-phenyl)-
vinyl]-4-methyl-1-p-tolyl-5,6-dihydro-1H-azocin-2-one
(5c). Pale white solid, Yield: 81%; mp 212–213 ꢀC; Anal.
Calcd for C31H31NO3: C, 79.97; H, 6.71; N, 3.01. Found: C,
80.05; H, 6.78; N, 2.96%. IR (KBr): nmax¼1663, 1510,
1
3.62%. IR (KBr): nmax¼1602, 1512, 1462, 1033 cmꢁ1; H
NMR (200 MHz, CDCl3, Me4Si): d¼2.39 (s, 3H, –CH3),
6.78 (d, J¼16.5 Hz, 1H, olefinic), 6.99 (d, J¼8.6 Hz,
2H, ArH), 7.05 (d, J¼15.9 Hz, 1H, olefinic), 7.18 (d,
J¼16.5 Hz, 1H, olefinic), 7.21 (d, J¼8.7 Hz, 2H, ArH),
7.19–7.31 (m, 4H, ArH), 7.35–7.52 (m, 4H, ArH), 7.66 (d,
J¼15.9 Hz, 1H, olefinic) ppm; 13C NMR (50.4 MHz,
CDCl3, Me4Si): d¼20.8, 114.2, 121.6, 122.5, 124.9, 126.5,
127.8, 128.4, 128.9, 129.1, 129.5, 134.8, 135.6, 137.6,
137.8, 141.5, 152.6, and 161.1. m/z: 391 (M+).
1330, 1290, 1030 cmꢁ1 1H NMR (200 MHz, CDCl3,
;
Me4Si): d¼1.83 (s, 3H, –CH3), 2.34 (s, 3H, –CH3), 2.39–
2.43 (m, 1H, –CH2), 2.64–2.74 (m, 1H, –CH2), 3.83 (s, 6H,
2ꢂ–OCH3), 4.09–4.13 (m, 1H, –CH), 5.88 (br s, 1H, olefinic),
6.01 (br s, 1H, olefinic), 6.45 (br s, 2H, olefinic), 6.77 (d,
J¼8.7 Hz, 2H, ArH), 6.88 (d, J¼8.8 Hz, 2H, ArH), 6.99–
7.41 (m, 8H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼20.8 (CH3), 25.9 (–CH3), 40.3 (–CH2), 42.9
(–CH), 55.3 (–OCH3), 96.2, 113.8, 114.4, 120.5, 121.8,
123.5, 125.6, 126.7, 129.4, 130.7, 131.8, 134.2, 135.2,
136.1, 138.4, 142.4, 156.5, 157.2, and 168.2. m/z: 465 (M+).
2.4.9. {3-(4-Chloro-phenyl)-1-[2-(4-chloro-phenyl)-
vinyl]-allylidene}-phenyl-amine (3i). Yellow solid, Yield:
71%; mp 131–132 ꢀC; Anal. Calcd for C23H17Cl2N: C,
73.02; H, 4.53; N, 3.70. Found: C, 72.94; H, 4.59; N,
1
3.61%. IR (KBr): nmax¼1603, 1510, 1464, 1033 cmꢁ1; H
2.4.13. 6-(4-Methoxy-phenyl)-8-[2-(4-methoxy-phenyl)-
vinyl]-1-p-tolyl-5,6-dihydro-1H-azocin-2-one (5d). Color-
less solid, Yield: 88%; mp 183–184 ꢀC; Anal. Calcd for
C30H29NO3: C, 79.80; H, 6.47; N, 3.10. Found: C, 79.85;
H, 6.51; N, 3.01%. IR (KBr): nmax¼1661, 1514, 1330,
NMR (200 MHz, CDCl3, Me4Si): d¼6.74 (d, J¼16.5 Hz,
1H, olefinic), 7.01 (d, J¼8.7 Hz, 2H, ArH), 7.03 (d,
J¼15.9 Hz, 1H, olefinic), 7.16 (d, J¼16.5 Hz, 1H, olefinic),
7.23 (d, J¼8.7 Hz, 2H, ArH), 7.14–7.35 (m, 4H, ArH), 7.36–
7.51 (m, 5H, ArH), 7.67 (d, J¼15.9 Hz, 1H, olefinic) ppm;
13C NMR (50.4 MHz, CDCl3, Me4Si): d¼114.1, 121.8,
122.6, 125.1, 126.3, 127.9, 128.2, 129.2, 129.9, 131.5,
134.5, 135.9, 137.2, 137.8, 141.8, 152.7, and 161.5. m/z:
377 (M+).
1293, 1030 cmꢁ1 1H NMR (200 MHz, CDCl3, Me4Si):
;
d¼2.34 (s, 3H, –CH3), 2.43–2.48 (m, 1H, –CH2), 2.74–
2.80 (m, 1H, –CH2), 3.82 (s, 6H, 2ꢂ–OCH3), 4.17–4.20
(m, 1H, –CH), 5.87–5.91 (m, 1H, olefinic), 5.97 (d,
J¼10.2 Hz, 1H, olefinic), 6.02 (br s, 1H, olefinic), 6.45
(br s, 2H, olefinic), 6.77 (d, J¼8.7 Hz, 2H, ArH), 6.89 (d,
J¼8.7 Hz, 2H, ArH), 6.99–7.42 (m, 8H, ArH) ppm; 13C
NMR (50.4 MHz, CDCl3, Me4Si): d¼21.0, 37.7, 40.6,
55.4, 96.1, 113.9, 114.4, 120.3, 121.6, 122.8, 125.9, 127.3,
129.4, 132.5, 133.4, 135.6, 136.7, 137.4, 138.8, 140.9,
141.8, 156.9, and 168.3. m/z: 451 (M+).
2.4.10. 1,6-Bis-(4-methoxy-phenyl)-8-[2-(4-methoxy-
phenyl)-vinyl]-4-methyl-5,6-dihydro-1H-azocinone (5a).
Colorless crystalline solid, Yield: 85%; mp 202–203 ꢀC;
Anal. Calcd for C31H31NO4: C, 77.31; H, 6.49; N, 2.91.
Found: C, 77.39; H, 6.53; N, 2.99. IR (KBr): nmax¼1662,
1508, 1338, 1299, 1031 cmꢁ1
;
1H NMR (200 MHz,
CDCl3, Me4Si): d¼1.84 (s, 3H, –CH3), 2.28 (unresolved
dd, J¼13.1 Hz, 1H, –CH2), 2.72 (unresolved dd, J¼
13.1 Hz, 1H, –CH2), 3.77 (s, 6H, 2ꢂ–OCH3), 3.83 (s, 3H,
–OCH3), 4.08–4.12 (m, 1H, –CH), 5.93 (d, J¼10.0 Hz,
2.4.14. 6-(4-Methoxy-phenyl)-8-[2-(4-methoxy-phenyl)-
vinyl]-4-methyl-1-phenyl-5,6-dihydro-1H-azocin-2-one
(5e). Colorless prismatic crystalline solid, Yield: 89%;
mp 196–197 ꢀC; Anal. Calcd for C30H29NO3: C, 79.80; H,

11272
P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
6.47; N, 3.10. Found: C, 79.89; H, 6.51; N, 3.14%. IR (KBr):
1H NMR
6.71; N, 3.45. Found: C, 85.83; H, 6.62; N, 3.39%. IR
;
1H
nmax¼1660, 1510, 1335, 1295, 1030 cmꢁ1
;
(KBr): nmax¼1664, 1513, 1331, 1292, 1030 cmꢁ1
(200 MHz, CDCl3, Me4Si): d¼1.82 (s, 3H, –CH3), 2.29
(unresolved dd, J¼13.1 Hz, 1H, –CH2), 2.74 (unresolved
dd, J¼13.1 Hz, 1H, –CH2), 3.79 (s, 6H, 2ꢂ–OCH3), 4.09–
4.14 (m, 1H, –CH), 5.94 (d, J¼10.1 Hz, 1H), 6.02 (br s,
1H, olefinic), 6.33 (d, J¼16.2 Hz, 1H), 6.44 (d,
J¼16.2 Hz, 1H), 6.79–7.39 (m, 13H, ArH) ppm; 13C NMR
(50.4 MHz, CDCl3, Me4Si): d¼26.2 (–CH3), 39.8 (–CH2),
42.9 (–CH), 55.2 (–OCH3), 96.2, 114.1, 114.5, 120.7, 121.8,
124.4, 125.8, 126.2, 128.5, 129.6, 132.3, 133.7, 135.5,
138.9, 141.8, 156.5, 158.4, 159.2, and 168.2. m/z: 451 (M+).
NMR (200 MHz, CDCl3, Me4Si): d¼1.83 (s, 3H, –CH3),
2.35 (s, 3H, –CH3), 2.25–2.33 (m, 1H, –CH2), 2.73–2.82
(m, 1H, –CH2), 4.15–4.19 (m, 1H, –CH), 5.99 (br s, 1H, ole-
finic), 6.05 (br s, 1H, olefinic), 6.53 (br s, 2H, olefinic), 6.78
(d, J¼8.8 Hz, 2H, ArH), 6.89 (d, J¼8.8 Hz, 2H, ArH), 7.10–
7.45 (m, 10H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼20.9, 25.8 (–CH3), 37.6 (–CH2), 40.7 (–CH),
96.1, 114.2, 121.5, 122.6, 123.3, 124.9, 126.7, 127.9, 129.8,
130.8, 131.9, 132.2, 132.8, 133.4, 134.5, 135.4, 142.9,
157.8, and 168.2. m/z: 405 (M+).
2.4.15. 6-(4-Methoxy-phenyl)-8-[2-(4-methoxy-phenyl)-
vinyl]-1-phenyl-5,6-dihydro-1H-azocin-2-one (5f). White
solid, Yield: 83%; mp 178–179 ꢀC; Anal. Calcd for
C29H27NO3: C, 79.61; H, 6.22; N, 3.20. Found: C, 79.68;
H, 6.29; N, 3.13%. IR (KBr): nmax¼1663, 1510, 1330,
2.4.19. 6-Phenyl-8-styryl-1-p-tolyl-5,6-dihydro-1H-azo-
cin-2-one (5j). Colorless solid, Yield: 80%; mp 159–
160 ꢀC; Anal. Calcd for C28H25NO: C, 85.90; H, 6.44; N,
3.58. Found: C, 86.01; H, 6.52; N, 3.49%. IR (KBr): nmax
¼
1
1662, 1511, 1330, 1299, 1030 cmꢁ1; H NMR (200 MHz,
CDCl3, Me4Si): d¼2.37 (s, 3H, –CH3), 2.35–2.43 (m, 1H,
–CH2), 2.72–2.80 (m, 1H, –CH2), 4.13–4.18 (m, 1H,
–CH), 5.92 (br s, 1H, olefinic), 6.07 (d, J¼8.9 Hz, 1H, ole-
finic), 6.17 (br s, 1H, olefinic), 6.53 (br s, 2H, olefinic),
6.79 (d, J¼8.8 Hz, 2H, ArH), 6.93 (d, J¼8.8 Hz, 2H,
ArH), 7.05–7.41 (m, 10H, ArH) ppm; 13C NMR
(50.4 MHz, CDCl3, Me4Si): d¼20.9, 37.5 (–CH2), 40.4
(–CH), 96.2, 114.2, 120.8, 122.5, 123.1, 123.7, 125.5,
126.8, 127.3, 127.9, 129.1, 130.3, 132.7, 134.5, 136.3,
136.8, 142.5, 158.1, and 168.3. m/z: 391 (M+).
1295, 1030 cmꢁ1 1H NMR (200 MHz, CDCl3, Me4Si):
;
d¼2.37–2.42 (m, 1H, –CH2), 2.73–2.79 (m, 1H, –CH2),
3.82 (s, 6H, 2ꢂ–OCH3), 4.16–4.21 (m, 1H, –CH), 5.93
(br s, 1H, olefinic), 6.05 (br s, 1H, olefinic), 6.43 (br s, 2H,
olefinic), 6.79 (d, J¼8.8 Hz, 2H, ArH), 6.87–7.39 (m,
11H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3, Me4Si):
d¼39.1, 41.1, 55.2, 96.1, 113.8, 114.2, 120.4, 121.8,
122.6, 124.9, 126.7, 128.3, 130.7, 133.2, 133.7, 135.1,
136.3, 137.2, 141.5, 143.5, 156.8, and 168.2. m/z: 437 (M+).
2.4.16. 1-(4-Methoxy-phenyl)-4-methyl-6-phenyl-8-sty-
ryl-5,6-dihydro-1H-azocin-2-one (5g). Pale white solid,
Yield: 72%; mp 217–218 ꢀC; Anal. Calcd for C29H27NO2:
C, 82.63; H, 6.46; N, 3.32. Found: C, 82.52; H, 6.41;
N, 3.24%. IR (KBr): nmax¼1661, 1517, 1333, 1295,
2.4.20. 4-Methyl-1,6-diphenyl-8-styryl-5,6-dihydro-1H-
azocin-2-one (5k). Colorless solid, Yield: 77%; mp 172–
173 ꢀC; Anal. Calcd for C28H25NO: C, 85.90; H, 6.44; N,
3.58. Found: C, 85.97; H, 6.49; N, 3.63%. IR (KBr): nmax
¼
1
1
1030 cmꢁ1; H NMR (200 MHz, CDCl3, Me4Si): d¼1.92
1661, 1510, 1326, 1290, 1030 cmꢁ1; H NMR (200 MHz,
CDCl3, Me4Si): d¼1.86 (s, 3H, –CH3), 2.30–2.36 (m, 1H,
–CH2), 2.74–2.81 (m, 1H, –CH2), 4.21–4.26 (m, 1H,
–CH), 5.91 (br s, 1H, olefinic), 6.02 (br s, 1H, olefinic),
6.56 (br s, 2H, olefinic), 6.79–7.15 (m, 6H, ArH), 7.20–
7.41 (m, 9H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼26.1 (–CH3), 37.6 (–CH2), 40.5 (–CH), 96.2,
114.3, 121.3, 122.6, 123.7, 125.5, 126.4, 127.2, 129.5,
130.6, 132.2, 132.8, 133.4, 134.5, 135.4, 136.1, 142.7,
156.7, and 168.4. m/z: 391 (M+).
(s, 3H, –CH3), 2.32–2.38 (m, 1H, –CH2), 2.76–2.79 (m,
1H, –CH2), 3.78 (s, 3H, –OCH3), 4.14–4.20 (m, 1H, –CH),
6.02 (br s, 1H, olefinic), 6.03 (br s, 1H, olefinic), 6.50
(br s, 2H, olefinic), 6.87 (d, J¼8.8 Hz, 2H, ArH), 7.16–
7.43 (m, 12H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼26.1 (–CH3), 37.9 (–CH2), 41.1(–CH), 55.3
(–OCH3), 96.2, 114.0, 120.2, 124.8, 126.5, 127.2, 127.9,
128.2, 130.3, 132.4, 132.9, 133.1, 136.5, 138.8, 140.2,
142.4, 145.8, 157.3, and 168.6. m/z: 421 (M+).
2.4.17. 1-(4-Methoxy-phenyl)-6-phenyl-8-styryl-5,6-di-
hydro-1H-azocin-2-one (5h). Colorless solid, Yield: 78%;
mp 189–190 ꢀC; Anal. Calcd for C28H25NO2: C, 82.53; H,
6.18; N, 3.44. Found: C, 82.57; H, 6.12; N, 3.36%. IR
2.4.21. 1,6-Diphenyl-8-styryl-5,6-dihydro-1H-azocin-2-
one (5l). Colorless solid, Yield: 76%; mp 208–209 ꢀC;
Anal. Calcd for C27H23NO: C, 85.91; H, 6.14; N, 3.71.
Found: C, 85.82; H, 6.19; N, 3.65%. IR (KBr): nmax¼1660,
1515, 1327, 1290, 1030 cmꢁ1; 1H NMR (200 MHz, CDCl3,
Me4Si): d¼2.35–2.41 (m, 1H, –CH2), 2.70–2.78 (m, 1H,
–CH2), 4.15–4.22 (m, 1H, –CH), 5.98 (br s, 1H, olefinic),
6.06 (d, J¼10.1 Hz, 1H, olefinic), 6.13 (br s, 1H, olefinic),
6.57 (br s, 2H, olefinic), 6.73–7.39 (m, 15H, ArH) ppm;
13C NMR (50.4 MHz, CDCl3, Me4Si): d¼37.9 (–CH2),
40.6 (–CH), 96.1, 113.9, 120.5, 121.9, 122.6, 123.2, 125.1,
125.4, 127.6, 129.4, 130.3, 131.6, 131.8, 133.6, 135.9,
136.8, 141.9, 157.8, and 168.5. m/z: 377(M+).
(KBr): nmax¼1660, 1515, 1330, 1295, 1030 cmꢁ1
;
1H
NMR (200 MHz, CDCl3, Me4Si): d¼2.42–2.48 (m, 1H,
–CH2), 2.80–2.83 (m, 1H, –CH2), 3.79 (s, 3H, –OCH3),
4.16–4.19 (m, 1H, –CH), 5.90 (br s, 1H, olefinic), 6.03 (d,
J¼10.0 Hz, 1H, olefinic), 6.17 (d, J¼10.0 Hz, 1H, olefinic),
6.52 (br s, 2H, olefinic), 6.89 (d, J¼8.8 Hz, 2H, ArH), 7.17–
7.46 (m, 12H, ArH) ppm; 13C NMR (50.4 MHz, CDCl3,
Me4Si): d¼37.4 (–CH2), 40.7 (–CH), 55.2 (–OCH3), 96.1,
114.1, 124.5, 126.4, 126.5, 127.0, 127.2, 127.9, 128.5,
129.1, 131.3, 131.5, 131.9, 133.1, 136.2, 139.1, 142.2,
157.8, and 168.1. m/z: 407 (M+).
Acknowledgements
2.4.18. 4-Methyl-6-phenyl-8-styryl-1-p-tolyl-5,6-di-
hydro-1H-azocin-2-one (5i). Colorless solid, Yield: 86%;
mp 167–168 ꢀC; Anal. Calcd for C29H27NO: C, 85.89; H,
Financial support to Mr. Parvesh Singh for this research
work by the Council of Scientific and Industrial Research

P. Singh et al. / Tetrahedron 62 (2006) 11267–11273
11273
Sengupta, D.; Mahajan, M. P. Tetrahedron 1994, 50, 7579; (c)
Dey, P. D.; Sharma, A. K.; Bharatam, P. V.; Mahajan, M. P.
Tetrahedron 1997, 53, 13829; (d) Jayakumar, S.; Kumar, V.;
Mahajan, M. P. Tetrahedron Lett. 2001, 42, 2235; (e) Mohan,
C.; Singh, P.; Mahajan, M. P. Tetrahedron 2005, 61, 10774;
(f) Singh, P.; Marwaha, A.; Singh, H.; Mahajan, M. P.
Tetrahedron 2005, 61, 11999; (g) Bhargava, G.; Mahajan,
M. P.; Saito, T.; Otani, T.; Kurashima, M.; Sakai, K. Eur. J.
Org. Chem. 2005, 2397.
(CSIR), New Delhi, under research project, 01(1872/03/
EMR-II) is gratefully acknowledged.
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