Synthesis of dibenzo[d,f]diazepinones and alkenylindolinones through ring transformation of 2H-pyran-2-one-3-carbonitriles by indolin-2-ones

Article abstract of DOI:10.1016/j.tet.2013.04.053

First ever synthesis of functionalized 5,7-dihydro-6H-dibenzo[d,f][1,3] diazepin-6-ones (6, 9) has been developed through base induced ring transformation of 2H-pyran-2-one-3-carbonitriles with indolin-2-ones. A protocol for alkenylating indolin-2-ones by

Full text of DOI:10.1016/j.tet.2013.04.053

Tetrahedron 69 (2013) 4857e4865
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Tetrahedron
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Synthesis of dibenzo[d,f]diazepinones and alkenylindolinones
through ring transformation of 2H-pyran-2-one-3-carbonitriles by
indolin-2-ones
Sandeep Kumar a, Ramendra Pratap b, Abhinav Kumar a, Brijesh Kumar c,
,
Vishnu K. Tandon a, Vishnu Ji Ram a
*
a Department of Chemistry, University of Lucknow, Lucknow 226007, India
b Department of Chemistry, North Campus, University of Delhi, New Delhi 110007, India
c Division of SAIF, Central Drug Research Institute, Lucknow 226001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 March 2013
Received in revised form 2 April 2013
Accepted 12 April 2013
Available online 18 April 2013
First ever synthesis of functionalized 5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-ones (6, 9) has been
developed through base induced ring transformation of 2H-pyran-2-one-3-carbonitriles with indolin-2-
ones. A protocol for alkenylating indolin-2-ones by 2H-pyran-2-one-3-carbonitriles has also been de-
veloped to obtain 3-alkenylindolin-2-ones (11). The nature and behaviour of intermolecular interactions
of these compounds are studied by single crystal-X-ray analysis and quantum chemical calculations.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Dibenzo[d,f][1,3]diazepine
Alkenylindolin-2-one
2H-Pyran-2-one
Indolin-2-one
Ring transformation
1. Introduction
N
NH
NH
Many seven membered cyclic compounds have been found to be
biologically active.1 In particular, diazepine analogues display di-
verse pharmacological activities, such as anxiolytic,2 hypnotic,2 HIV
protease inhibitors3 and as cardiovascular.4 An extensive literature
survey revealed that the chemistry and pharmacology of 5H-
dibenzo[d,f][1,3]diazepine (I) is not explored extensively5 except
functionalized at position 6 by alkyl,6e9 aryl,10e12 and alkoxy12
substituents. Besides these, compounds with keto13 and thio
functional groups (IIa, b) have also been synthesized and re-
ported,14 Fig. 1.
N
R
X
XH
NH
NH
II'
I
II
a. X = O
b. X = S
Fig. 1. Dibenzo[d,f][1,3]diazepines.
The majority of procedures reported for the synthesis of 5H-
dibenzo[d,f][1,3]diazepine ring system involve the reaction of
biphenyl-2,20-diamine with 1,10-dielectrophilic reagents, such as
cyanogen bromide,15a benzamidine hydrochloride,15b,c benzoni-
trile15d or methyl arylcarbimidothioates.15e Recently, a new pro-
cedure for the construction of this ring system has been developed16
from the reaction of 2-anilino-2-[oxido(phenyl)imino]-N-pyridin-
2-ylacetamides with biphenyl-2,20-diamine. However, this pro-
cedure is also not devoid of biphenyl-2,20-diamine as a precursor.
The limitation and dearth of synthetic procedures for the
construction of 5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-ones
and respective thiones, belie their importance as useful pharma-
ceuticals and intermediates for making more functionalized sys-
tems. Earlier, 5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-one (II)
was prepared by heating biphenyl-2,20-diamine with urea. Under
the proper equilibrium conditions the exocyclic ketone may tau-
tomerize to the endocyclic 5H-dibenzo[d,f][1,3]diazepin-6-ol
(II0).17 Recently, transition metal catalyzed biscarbonylation of
* Corresponding author. Tel.: þ91 522 2960779; fax: þ91 522 2623405; e-mail
address: vjiram@yahoo.com (V.J. Ram).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.053

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S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
2,2-dinitro-1,1-biphenyl with carbon monoxide, resulted in ring
closure to form 5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-one
in moderate yields.18,19 Exocyclic [1,3]diazepin-6-thione (IIb)
was first prepared in low yield by Le Fevre in 1929 by treating
biphenyl-2,20-diamine with carbon disulfide in refluxing etha-
nol.14 However, a modification in the solvent system from ethanol
to pyridine increased the yield up to 72%. Recently, use of thio-
phosgene as a reagent has also been reported20 for the synthesis
of [1,3]diazepin-6-thione.
3-Alkenylindolin-2-ones are an important class of heterocycles,
widely present in nature and known for their anticancer,21 antibac-
terial,22 antifungal,23 antiviral,23a antipyretic,24 anti-inflammatory25
andanalgesic25 properties. Though there are numerous routes for the
synthesis of this class of compounds in which condensation of
indolin-2-one with aldehyde is prominent. Condensation of isatin
with reactive methylene compounds, such as malononitrile, ethyl
cyanoacetate etc. is another option to synthesize alkenylindolin-2-
ones. Over the past 5e10 years, numerous metal catalyzed synthe-
ses26 of 3-alkenylindolin-2-ones have emerged.
product on silica gel using hexane/chloroform (60:40) as eluent, 1-
aryl-3-(methylthio)-5H-dibenzo[d,f][1,3]diazepin-6(7H)-ones (6)
were obtained in 38e58% yields in lieu of an expected carbazole
derivate (8) (Scheme 2). The structure of the isolated compound
SMe
SMe
CN
O
X
t
t
BuOK/ BuOH
O
Reflux
Ar
NH
N
H
Ar
O
3
O
5
NH
X
t
t
BuOK/ BuOH
6
X
Ar
6
Reflux
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
phenyl
SMe
4-bromophenyl
2-naphthyl
CN
NH
4-chlorophenyl
4-methylphenyl
4-methoxyphenyl
4-pyridyl
Ar
g
h
i
2-furyl
2-thiophenyl
j
4-acetamidophenyl
X
k
Br phenyl
2. Results and discussion
2.1. Chemistry
8
Scheme 2. Synthesis of 1-aryl-3-methylthio-5,7-dihydro-6H-dibenzo[d,f][1,3]dia-
zepin-6-one (6).
We have developed a new route, which does not require bi-
phenyl-2,20-diamine as a precursor but also provides an opportu-
nity to functionalize not only the 1,3-diazapine ring but also other
aromatic rings present in the molecular scaffold. The synthetic
methodology for the construction of 5,7-dihydro-6H-dibenzo[d,f]
[1,3]diazepin-6-one is based on base induced ring transformation
of suitably functionalized 2H-pyran-2-one-3-carbonitriles by
indolin-2-ones. An intensive literature survey revealed that ring
transformation of 2H-pyan-2-one-3-carbonitriles by indolin-2-one
is the first report and has not been explored so far.
was corroborated by spectral analyses and single crystal X-ray
diffraction, (Fig. 2). Optimization of the reaction condition, i.e., re-
duction in reflux period from 6 to 3 h, resulted poor yield (12%) of
desired compound with recovery of reactants while an increase in
reflux period from 6 to 10 h did not improve the yields. However,
best yields of 6 were achieved when reaction was refluxed for 6 h.
6-Aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles (3) as the
precursors for the synthesis of highly functionalized 3-
methylthiodibenzo[d,f][1,3]diazepin-6-ones (6) were obtained27
from the reaction of methyl 2-cyano-3,3-dimethylthioacrylate28 (1)
and aryl methyl ketone (2) using powdered KOH as a base in
DMF at room temperature. 6-aryl-4-sec-amino-2H-pyran-2-one-3-
carbonitriles (4), obtained from amination of 3 with sec-amine in
boilingethanol, were used furtherasprecursors forthesynthesis of 1-
aryl-3-sec-aminodibenzo[d,f][1,3]diazepin-6-ones (9) (Scheme 1).29
N
SMe
NC
COOMe
Ar-COCH3
SMe
CN
O
CN
O
KOH
DMF
HN
+
EtOH
MeS
Ar
O
3
Ar
O
4
1
2
3,4
Ar
phenyl
4-methylphenyl
4-methoxyphenyl
4-chlorophenyl
3-acetylaminophenyl
4-acetylaminophenyl
4-pyridyl
4-(dimethylaminoethoxy)phenyl
4-flurophenyl
a
b
c
d
e
f
g
h
i
Scheme 1. Synthesis of substituted-2H-pyran-2-ones.
Reaction of 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitiles
(3) with indolin-2-one (5) was carried out in tert-butanol at reflux
t
temperature using BuOK as a base proceeded smoothly and was
Fig. 2. ORTEP diagrams of 6a and 6e at 30% probability with atom numbering scheme.
complete within 6 h. After column chromatography of the crude
The solvent molecules are removed for clarity.

S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
4859
SMe
A
plausible mechanism for the formation of 1-aryl-3-
SMe
OMe
CN
O
methylthio-5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-one is il-
lustrated in Scheme 3. The position 6 of the 2-pyranone is highly
vulnerable to nucleophilic attack due to extended conjugation to
Ar
O
3
NH
NH
Ar
Ar
O
+
N
H
O
O
NaOMe
MeOH,
Reflux
NH
NH
5
O
SMe
O
MeS
7
CN
+
O
6
CN
tBuOK/ tBuOH
6/7
O
NaOMe
MeOH,
Reflux
N
Ar
phenyl
Ar
N
H
Ar
O
3
CN
O
O
a
b
c
d
4-bromophenyl
2-naphthyl
5
NH
Ar
O
4
4-chlorophenyl
t
tBuOK/ BuOH
O
O
MeS
Ar
MeS
N
N
-CO2
CN
O
O
Ar
9
Ar
NH
Ar
a
4-chlorophenyl
phenyl
NH
O
b
c
d
NH
NH
4-bromophenyl
4-methoxyphenyl
t
BuOK/tBuOH
N
9
MeS
Scheme 4. Synthesis of mixture of 1-aryl-3-methylthio/sec-amino-5,7-dihydro-6H-
dibenzo[d,f][1,3]diazepin-6-ones (6, 9) and 1-aryl-3-methoxy-5,7-dihydro-6H-dibenzo
[d,f][1,3]diazepin-6-ones (7).
MeS
Ar
C
NH
t
BuOK/tBuOH
O
O
Ar
NH
NH
carbonitriles (3) by indolin-2-one (5) in freshly prepared NaOMe at
reflux temperature is obvious to deliver 7 along with 6.
Interestingly, utilization of 6-aryl-4-sec-amino-2H-pyran-2-
one-3-carbonitriles (4) containing the secondary amine group
having poorer leaving group character under similar conditions
afforded exclusively 1-aryl-3-sec-amino-5,7-dihydro-6H-dibenzo
[d,f][1,3]diazapin-6-ones (9) (Scheme 4).
In search of an efficient and novel route to synthesize 3-
alkenylindolin-2-ones, a reaction of 6-aryl-4-methylthio-2H-py-
ran-2-one-3-carbonitriles (3) and indolin-2-one (5) was performed
in NaH/THF at reflux temperature, which gave an entirely different
product, other than 1-aryl-5,7-dihydro-6H-dibenzo[d,f][1,3]dia-
zepin-6-ones (6) and carbazole derivatives (8). Finally, the com-
pounds isolated were characterized as 3-alkenylindolin-2-one (11)
by spectroscopic and X-ray diffraction studies.
SMe
MeS
C
NH
NH
Ar
Ar
O
O
NH
NH
6
Scheme 3. A plausible mechanism for the formation of products 1-aryl-5,7-dihydro-
6H-dibenzo[d,f][1,3]diazepin-6-ones (6).
C]O at position 2 and also to the CN, an electron withdrawing
substituent present at position 3. Possibly, the reaction is initiated
with formation of the Michael adduct by attack of carbanion,
formed from indolin-2-one in the presence of base at position 6 of
the pyran-2-one ring with liberation of carbon dioxide followed by
ring closure and ring expansion to yield 1-aryl-3-(methylthio)-5H-
dibenzo[d,f][1,3]diazepin-6(7H)-one (6), Scheme 3.
On the other hand, heating the mixture of 3 with 5 in methanol
as a solvent and sodium methoxide as a base at reflux temperature
over 10 h afforded a mixture of 1-aryl-3-methylthio-5,7-dihydro-
6H-dibenzo[d,f][1,3]diazepin-6-one (6) and 1-aryl-3-methoxy-5,7-
dihydro-6H-dibenzo[d,f][1,3]diazepin-6-one (7) in 46e66% yields
after column chromatography of the crude product on silica gel
using hexane/chloroform (60:40) as eluent (Scheme 4). The ratio of
both the compounds in the mixture was ascertained by 1H NMR.
With the exception of few cases, the methoxy analogues (7) were
mostly obtained in 5e11% yields. We also tried to convert 6 to 7 by
increasing the amount of base and reflux period from 5 to 25 h but
complete conversion did not occur. Reduction in reaction time led
to isolation of unreacted starting material.
Based on the suggested mechanism depicted in Scheme 5,
products 11 seem to have been formed from the initially generated
SMe
Ar
CN
SMe
CN
NaH/THF
Reflux
O
+
O
N
H
N
H
Ar
O
3
O
5
10
11
a
b
phenyl
4-flurophenyl
SMe
SMe
Ar
Ar
CN
CN
O
O
N
H
N
H
12
11
The formation of 1-phenyl-3-methoxy-5,7-dihydro-6H-dibenzo
[d,f][1,3]diazepin-6-one (7) along with compound 6 is attributed to
the exchange of eSMe by eOMe in 3 to form 6-aryl-4-methoxy-2H-
pyran-2-one-3-carbonitriles under applied reaction conditions. The
Scheme 5. Synthesis of 3-alkenyindolin-2-ones (11).
intermediate 10. The structural ambiguity of tautomers 10, 11 and
12 was resolved by single crystal X-ray diffraction analysis (vide
infra) and ultimately the structure was assigned as 11 (Fig. 3).
The reaction is initiated by attack of carbanion generated from
indolin-2-one (5) at C-6 of the pyran-2-one forming Michael
transformation of
3 to 6-aryl-4-methoxy-2H-pyran-2-one-3-
carbonitriles is reported earlier by Tominaga et al.27c in the pres-
ence of sodium methoxide in methanol at reflux temperature. Thus,
the ring transformation of 6-aryl-4-methylthio-2H-pyran-2-one-3-

4860
S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
Fig. 5. Centrosymmetric dimer of 6e bound by pair of weak NeH/O intermolecular
interactions (symm. op. 1ꢁx,ꢁy,1ꢁz).
Fig. 3. ORTEP diagram of 11a at 30% probability with atom numbering scheme.
adduct followed by elimination of carbon dioxide to form 3-
alkenylindolin-2-one (11) without undergoing further cyclization
to yield 6. This discrepancy is possibly due to a large difference in
polarity of both the solvents as dielectric constant of THF is 7.48
while for methanol is 32.7, Scheme 5.
2.2. Structural description
The molecular view (ORTEP) for the three compounds 6a, 6e and
11a with atom numbering scheme is presented in Figs. 2 and 3. In
the case of 6a, the 1,3-diazepin-2-one ring B is puckered and has
neither adopted the boat-chair nor crown conformation. This is due
to the fusion of aromatic rings with the 1,3-diazepine ring, i.e., the
phenyl ring A and methylthiophenyl ring C. The dihedral angle
between the rings A and C is 43.80ꢀ; rings C and D is 47.42ꢀ while
between A and D is 49.98ꢀ. In the case of 6e, the 1,3-diazepin-2-one
ring B is puckered and has adopted neither boat-chair nor crown
conformation. The dihedral angle between rings A and C is 42.73ꢀ;
C and D is 56.99ꢀ and A and D is 59.87ꢀ. In 11a, rings A and B are
almost coplanar with respect to each other displaying a dihedral
angle 2.72ꢀ. However, the dihedral angle between the rings A and C
is 74.18ꢀ. The bond lengths C2eC9, C9eC10, C9eC16, C16eC17 and
C17eC18 have dimensions 1.339(3), 1.496(3), 1.506(3), 1.500(3) and
Fig. 6. Centrosymmetric dimer of 11a bound by pair of weak NeH/O intermolecular
interactions (symm. op. 1ꢁx,ꢁy,ꢁz).
centrosymmetric dimer bound by NeH/O interactions have H/O
ꢀ
ꢀ
interaction distance of 2.005 A and the <NeH/O is 171.13 .
The crystal structures of the compounds 6a, 6e and 11a as dis-
cussed above are good examples of the molecular interactions that
lead to interesting supramolecular aggregates in the solid state. In
order to analyze the various interactions that lead to the crystal
structure, interaction energies and electrostatic potentials have been
calculated fordimer fragments (Fig. 7). The analysis of the interaction
energy in the crystal structures of 6a, 6e and 11a by means of dimer
ꢀ
1.337(3) A, respectively. The angles <C2eC9eC10, <C2eC9eC16,
<C9eC16eC17 and <C16eC17eC18 have magnitudes of 122.6(2)ꢀ,
122.8(2)ꢀ, 112.79(18)ꢀ and 122.6(2), respectively.
The supramolecular aggregations in 6a, 6e and 11a are stabilized
by a pair of weak NeH/O interactions (Figs. 4e6) that led to the
formation of centrosymmetric dimers. In the case of 6a the H/O
ꢀ
interaction distance is of 2.105 A and the <NeH/O of magnitude
176.44ꢀ is almost linear. In the case of 6e, H/O interaction is of
ꢀ
ꢀ
distance 2.243 A and the <NeH/O is 166.45 . For 11a, the
Fig. 4. Centrosymmetric dimer of 6a bound by pair of weak NeH/O intermolecular
Fig. 7. Electrostatic potential surfaces for 6a, 6e and 11a. The blue/yellow colours in-
interactions.
dicate the low and high charge density.

S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
4861
Table 1
unit bound by NeH/O interactions at the DFT level of theory yields
the interaction energies ꢁ14.51, ꢁ14.62 and ꢁ13.56 kcal/mol,
respectively.
Selected topographical features of NeH/O interactions computed at B3LYP/6-31G**
level of theory
Compound
rbcp
Vr2
E
H (au)
To confirm further the presence of NeH/O interaction, bond
critical points (bcp) were calculated for all the three dimers by
using the Atoms in Molecules Theory.30 The bond critical points
observed between the H and O atoms confirm the presence of
NeH/O between two molecules of 6a, 6e and 11a (Fig. 8). The
bcp
6a
6e
11a
þ0.048570
þ0.048226
þ0.048751
þ0.110629
þ0.110666
þ0.106262
þ0.002298
þ0.002526
þ0.005152
þ0.014785
þ0.014606
þ0.015339
value of electron density (
r
); Laplacian ðV2r Þ; bond ellipticity (ε)
bcp
ellipticity (ε) measures the extent to which the density is prefer-
entially accumulated in a given plane containing the bond path. The
ε values for all the three compounds indicate that these NeH/O
interactions are not cylindrically symmetrical in nature.
and total energy density (H) at the bond critical point for NeH/O
interactions in 6a, 6e and 11a are presented in Table 1. From table it
is evident that the electron density for all the three compounds at
bond critical point (rbcp) are less than þ0.10 au, which indicates
a closed shell hydrogen bonding interactions. Additionally, the
Laplacian of the electron density V2r in all the three cases are
greater than zero, which indicates thebcdpepletion of electron density
in the region of contact between the H/O atoms. The bond
3. Conclusions
In conclusion, we have developed a simple, efficient and eco-
nomical procedure for the construction of highly functionalized
5,7-dihydro-6H-dibenzo[d,f][1,3]diazepin-6-ones (6, 9) through
unusual ring transformation of 2H-pyran-2-one-3-carbonitriles by
indolin-2-ones without using biphenyl-2,20-diamine as a precursor.
This methodology provides an opportunity to make 5,7-dihydro-
6H-dibenzo[d,f][1,3]diazepin-6-ones with substitution not only in
1,3-diazepine ring but also in all aromatic rings. The most impor-
tant feature of this protocol is that it replaces the use of biphenyl-
2,20-diamine as a key precursor for the construction of 5,7-dihydro-
6H-dibenzo[d,f][1,3]diazepin-6-ones.The versatility of pyran-2-one
as precursor is not limited to the synthesis of functionalized 1,3-
diazepines but also useful as a reagent for the alkenylation of
indolin-2-ones. Thus, it opens a new avenue for an efficient syn-
thesis of 3-alkenyindolin-2-ones. The single crystal-X-ray analysis
revealed that these molecules form centrosymmetric dimers bound
by NeH/O interactions. Additionally, the interaction angles were
close to 180ꢀ, indicating strong interactions and this is established
by quantum chemical calculations.
4. Experimental section
4.1. General
6-Aryl-2H-pyran-2-one-3-carbonitriles (3 and 4) are prepared
as reported in literature.27e29 Indolin-2-one was purchased from
Sigma Aldrich. Commercially available reagents were used without
further purification. 1H and 13C NMR spectra were recorded on
a Bruker 400 MHz and 300 MHz NMR spectrophotometer. CDCl3
and DMSO-d6 were used as solvents. Chemical shifts are reported in
parts per million (
the middle peak of the solvent (CDCl3) (
d
-value) from Me4Si (
d
¼0 ppm for 1H) or based on
d
¼77.00 ppm for 13C NMR)
as an internal standard. Signal patterns are indicated as s, singlet; d,
doublet; dd, double doublet; t, triplet; m, multiplet; bs, broad sin-
glet; bm, broad multiplet. Coupling constant (J) is given in Hertz
(Hz). Infrared (IR) spectra were recorded on a PerkineElmer AX-1
spectrophotometer in KBr disc and reported in wave number
(cmꢁ1). 6520 Q-TOF (HRMS) Agilent spectrometer was used for
mass spectral analysis from Sophisticated Analytical Instrumental
Facility Lab in CDRI, Lucknow, India.
4.2. General procedure for the synthesis of 1-aryl-3-(methyl-
thio)-5H-dibenzo[d,f][1,3]diazepin-6(7H)-ones (6)
A mixture of indolin-2-one 5 (0.146 g, 1.1 mmol), 2H-pyran-3-
carbonitriles 3 (1.0 mmol) and potassium tert-butoxide (0.24 g,
2.1 mmol), in dry tert-butanol (10 mL) was refluxed for 6 h. Excess
of solvent was removed and the viscous mass obtained was poured
onto the crushed ice with vigorous stirring and thereafter neu-
tralized with dil aq HCl. The precipitate obtained was filtered, dried
Fig. 8. Molecular graphs for the centrosymmetric dimers of 6a, 6e and 11a by AIM
calculations using B3LYP/6-31G** level of theory.

4862
S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
and the crude thus obtained was purified on silica gel column using
hexane/chloroform (60:40) as eluent, to yield 6.
HRMS (ESI): calcd for C20H16ClN2OS [MH]þ 367.0671; found
367.0675.
4.2.1. 3-(Methylthio)-1-phenyl-5H-dibenzo[d,f][1,3]diazepin-6(7H)-
one (6a). A mixture of indolin-2-one 5 (0.146 g, 1.1 mmol), 4-
(methylthio)-2-oxo-6-phenyl-2H-pyran-3-carbonitrile 3a (0.243 g,
1.0 mmol) and potassium tert-butoxide (0.24 g, 2.1 mmol), in dry
tert-butanol (10 mL) was refluxed for 6 h. Excess of solvent was
removed and the viscous mass obtained was poured onto the
crushed ice with vigorous stirring and thereafter neutralized with
dil aq HCl. The precipitate obtained was filtered, dried and the
crude thus obtained was purified on silica gel column using hex-
ane/chloroform (60:40) as eluent, to yield 6a as a white powder,
yield, 137 mg, (41%). Mp 235e236 ꢀC. Rf (30% EtOAc/Hexane) 0.54.
4.2.5. 1-(4-Methyphenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6e). It was obtained as a white powder from the
reaction of indolin-2-one 5 (0.146 g, 1.1 mmol), 4-(methylthio)-2-
oxo-6-p-tolyl-2H-pyran-3-carbonitrile 3e (0.257 g, 1 mmol) and
potassium tert-butoxide (0.24 g, 2.1 mmol) in tert-butanol. Yield,
131 mg, (38%). Mp 271e273 ꢀC. Rf (30% EtOAc/Hexane) 0.75. nmax
(KBr) 3231, 3125, 1701, 1557, 1390, 1236, 1113 cmꢁ1
(400 MHz, DMSO-d6):
¼2.24 (s, 3H, ArCH3), 2.48 (s, 3H, SCH3),
6.51e6.62 (m, 2H, ArH), 6.94e7.06 (m, 8H, ArH), 8.72 (s, 1H, NHCO),
8.88 (s, 1H, CONH) ppm. 13C NMR (100 MHz, DMSO-d6):
.
1H NMR
d
d
¼14.4,
20.6, 116.2, 121.0, 122.6, 123.1, 123.8, 127.5, 128.7, 128.9, 129.4, 132.5,
136.1, 138.1, 138.6, 140.7, 142.1, 143.1, 164.8 ppm. HRMS (ESI): calcd
for C21H19N2OS [MH]þ 347.1218; found 347.1214.
nmax (KBr) 3246, 1695, 1560, 1360, 1219 cmꢁ1
DMSO-d6):
¼2.49 (s, 3H, SCH3), 6.45e6.55 (m, 2H, ArH), 6.90e7.16
(m, 9H, ArH), 8.70 (d, J¼2.2 Hz, 1H, NHCO), 8.85 (d, J¼2.2 Hz, 1H,
CONH) ppm. 13C NMR (100 MHz, DMSO-d6):
.
1H NMR (400 MHz,
d
d
¼14.4, 116.4, 121.1,
4.2.6. 1-(4-Methoxyphenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6f). It was obtained from the reaction of indolin-
2-one 5 (0.146 g, 1.1 mmol), 6-(4-methoxyphenyl)-4-(methylthio)-
2-oxo-2H-pyran-3-carbonitrile 3f (0.273 g, 1 mmol) and potassium
tert-butoxide (0.24 g, 2.1 mmol) in tert-butanol as a white powder,
yield, 170 mg, (47%). Mp 236e238 ꢀC. Rf (30% EtOAc/Hexane) 0.52.
nmax (KBr) 3234, 3132, 1700, 1512, 1388, 1244, 1171 cmꢁ1. 1H NMR
122.5, 123.2, 124.1, 126.9, 127.6, 128.2, 128.6, 129.5, 132.5, 138.7,
140.8, 141.1, 142.1, 142.6, 164.8 ppm. HRMS (ESI): calcd for
C20H17N2OS [MH]þ 333.1061; found 333.1058.
4.2.2. 1-(4-Bromophenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6b). It was obtained as a white solid from the
reaction of indolin-2-one 5 (0.146 g,1.1 mmol), 6-(4-bromophenyl)-
4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile 3b (0.322 g,
1 mmol) and potassium tert-butoxide (0.24 g, 2.1 mmol) in dry tert-
butanol. Yield, 180 mg, (44%). Mp >300 ꢀC. Rf (30% EtOAc/Hexane)
(400 MHz, DMSO-d6):
d
¼2.49 (s, 3H, ArOCH3), 3.69 (s, 3H, SCH3),
6.54 (m, 1H, ArH), 6.63 (m, 1H, ArH), 6.77 (d, J¼8.8 Hz, 2H, ArH),
6.91e7.05 (m, 6H, ArH), 8.70 (s, 1H, NHCO), 8.86 (s, 1H, CONH) ppm.
13C NMR (100 MHz, DMSO-d6):
d¼14.4, 55.1, 113.7, 116.0, 121.1,
0.52. nmax (KBr) 3238, 3136, 1702, 1518, 1388, 1252, 1112 cmꢁ1
NMR (400 MHz, DMSO-d6):
.
1H
122.6, 123.0, 123.7, 127.5, 130.7, 132.5, 132.6, 133.3, 138.5, 140.5,
141.7, 143.1, 158.2, 164.7 ppm. HRMS (ESI): calcd for C21H19N2O2S
[MH]þ 363.1167; found 363.1164.
d
¼2.49 (s, 3H, SCH3), 6.50 (d, J¼8.0 Hz,
1H, ArH), 6.65 (t, J¼6.8 Hz, 1H, ArH), 6.95e7.11 (m, 6H, ArH), 7.40 (d,
J¼8.0 Hz, 2H, ArH), 8.77 (s, 1H, NHCO), 8.92 (s, 1H, CONH) ppm. 13C
NMR (100 MHz, DMSO-d6):
d
¼14.4, 116.6, 120.2, 121.2, 122.7, 123.0,
4.2.7. 3-(Methylthio)-1-(pyridin-4-yl)-5H-dibenzo[d,f][1,3]diazepin-
6(7H)-one (6g). It was obtained from the reaction of indolin-2-one
5 (0.146 g, 1.1 mmol), 4-(methylthio)-2-oxo-6-(pyridin-4-yl)-2H-
pyran-3-carbonitrile 3g (0.244 g, 1 mmol) and potassium tert-
butoxide (0.24 g, 2.1 mmol) in tert-butanol, as a white powder,
yield, 143 mg, (43%). Mp >300 ꢀC. Rf (60% EtOAc/Hexane) 0.68. nmax
(KBr) 3213, 3140, 1695, 1591, 1497, 1377, 1228, 1120 cmꢁ1. 1H NMR
124.1,127.8,128.2,131.2,131.7,132.6,138.9,140.4,140.8,140.9,143.2,
164.7 ppm. HRMS (ESI): calcd for C20H16BrN2OS [MH]þ 411.0167;
found 411.0165.
4.2.3. 3-(Methylthio)-1-(naphthalen-2-yl)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6c). It was prepared from the reaction of indolin-
2-one 5 (0.146 g, 1.1 mmol), 4-(methylthio)-6-(naphthalen-2-yl)-2-
oxo-2H-pyran-3-carbonitrile 3c (0.293 g, 1 mmol) and potassium
tert-butoxide (0.24 g, 2.1 mmol) in tert-butanol as a white amor-
phous solid. Yield, 183 mg, (48%). Mp 246e248 ꢀC. Rf (30% EtOAc/
Hexane) 0.42. nmax (KBr) 3235, 3130, 1701, 1557, 1390, 1236,
(400 MHz, DMSO-d6):
d
¼2.49 (s, 3H, SCH3), 6.45 (m, 1H, ArH), 6.61
(m, 1H, ArH), 6.97e7.07 (m, 6H, ArH), 8.36 (d, J¼6.0 Hz, 2H, ArH),
8.78 (s, 1H, NHCO), 8.92 (s, 1H, CONH) ppm. 13C NMR (100 MHz,
DMSO-d6):
d
¼14.4, 117.3, 121.2, 122.7, 123.0, 123.9, 124.5, 127.9,
128.1, 132.6, 139.3, 139.4, 140.9, 143.2, 148.8, 149.5, 164.6 ppm.
HRMS (ESI): calcd for C19H16N3OS [MH]þ 334.1014; found 334.1013.
1129 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
d
¼2.45 (s, 3H, SCH3),
6.45e6.52 (m, 2H, ArH), 7.00e7.07 (m, 5H, ArH), 7.43 (t, J¼4.0 Hz,
2H, ArH), 7.61 (m, 1H, ArH), 7.77 (d, J¼6.0 Hz, 3H, ArH), 8.76 (s, 1H,
NHCO), 8.92 (s, 1H, CONH) ppm. 13C NMR (100 MHz, DMSO-d6):
4.2.8. 1-(Furan-2-yl)-3-(methylthio)-5H-dibenzo[d,f][1,3]diazepin-
6(7H)-one (6h). It was isolated from the reaction of indolin-2-one 5
(0.146 g, 1.1 mmol), 6-(furan-2-yl)-4-(methylthio)-2-oxo-2H-py-
ran-3-carbonitrile 3h (0.233 g, 1 mmol) and potassium tert-but-
oxide (0.24 g, 2.1 mmol) as white amorphous powder, yield,187 mg,
(58%). Mp 230e232 ꢀC. Rf (30% EtOAc/Hexane) 0.49. nmax (KBr)
d
¼14.5, 116.6, 121.08, 122.6, 123.6, 124.1, 126.2, 127.0, 127.4,
127.7, 128.0, 128.1, 131.7, 132.5, 132.8, 138.8, 141.0, 142.1, 143.2,
164.8; HRMS (ESI): calcd for C24H19N2OS [MH]þ 383.1218; found
383.1223.
3347, 3241, 3130, 1698, 1562, 1390, 1237, 1161 cmꢁ1
.
1H NMR
4.2.4. 1-(4-Chlorophenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6d). It was isolated from the reaction of indolin-
2-one 5 (0.146 g, 1.1 mmol), 6-(4-chlorophenyl)-4-(methylthio)-2-
oxo-2H-pyran-3-carbonitrile 3d (0.278 g, 1 mmol) and potassium
tert-butoxide (0.24 g, 2.1 mmol) in dry tert-butanol as an amor-
phous powder. Yield, 154 mg, (42%). Mp 288e290 ꢀC. Rf (30%
EtOAc/Hexane) 0.51. nmax (KBr) 3229, 3127, 1701, 1560, 1390,
(400 MHz, DMSO-d6):
ArH), 6.34e6.45 (m, 2H, ArH), 6.70e6.82 (m, 2H, ArH), 7.03e7.17
d
¼2.49 (s, 3H, SCH3), 6.35 (d, J¼2.4 Hz, 2H,
(m, 4H, ArH), 7.47 (s,1H, ArH), 8.74 (s,1H, NHCO), 8.89 (s,1H, CONH)
ppm. 13C NMR (100 MHz, DMSO-d6):
d¼14.4, 109.5, 111.6, 116.9,
121.3, 123.0, 127.9, 128.8, 130.5, 130.7, 138.9, 140.3, 142.8, 143.2,
152.8, 164.5 ppm. HRMS (ESI): calcd for C18H15N2O2S [MH]þ
323.0854; found 323.0847.
1238, 1091 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
d
¼2.49 (s, 3H,
CH3), 6.49 (d, J¼8.0 Hz, 1H, ArH), 6.65 (t, J¼6.8 Hz, 1H, ArH), 6.95
(s, 1H, ArH), 7.07 (m, 5H, ArH), 7.26 (d, J¼8.0 Hz, 2H, ArH), 8.77 (s,
1H, NHCO), 8.92 (s, 1H, CONH) ppm. 13C NMR (100 MHz,
4.2.9. 3-(Methylthio)-1-(thiophen-2-yl)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6i). It was obtained from the reaction of indolin-
2-one 5 (0.146 g, 1.1 mmol), 4-(methylthio)-2-oxo-6-(thiophen-2-
yl)-2H-pyran-3-carbonitrile 3i (0.249 g, 1 mmol) and potassium
tert-butoxide (0.24 g, 2.1 mmol) as a white amorphous powder,
DMSO-d6):
d
¼14.4, 116.6, 121.1, 122.7, 123.0, 124.1, 127.8, 128.3,
131.3, 131.6, 132.5, 138.9, 140.0, 140.7, 140.9, 143.2, 164.7 ppm.

S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
4863
yield, 176 mg, (52%). Mp 265e270 ꢀC. Rf (30% EtOAc/Hexane) 0.45.
nmax (KBr) 3234, 3102, 1694, 1553, 1397, 1235, 1123 cmꢁ1. 1H NMR
(m, 2H, ArH), 6.94e7.11 (m, 6H, ArH), 7.40e7.42 (d, J¼8.4 Hz, 2H,
ArH), 8.78 (s, 1H, NHCO), 8.93 (s, 1H, CONH) ppm. HRMS (ESI): calcd
for C20H16BrN2OS [MH]þ 411.0167 found 411.0165. 7b: 1H NMR
(400 MHz, DMSO-d6):
7.45 (m, 1H, ArH), 8.75 (s, 1H, NHCO), 8.90 (s, 1H, CONH) ppm. 13C
NMR (100 MHz, DMSO-d6):
d
¼2.49 (s, 3H, SCH3), 6.74e7.16 (m, 8H, ArH),
(400 MHz, DMSO-d6):
d¼3.79 (s, 3H, OCH3), 6.49e6.70 (m, 2H,
d
¼14.4, 105.5, 116.7, 121.1, 122.8, 123.2,
ArH), 6.95e7.07 (m, 5H, ArH), 7.20 (s, 3H, ArH), 8.75 (s, 1H, NHCO),
8.89 (s, 1H, CONH) ppm. HRMS (ESI): calcd for C20H16BrN2O2 [MH]þ
395.0395; found 395.0397.
123.9, 127.2, 127.3, 128.0, 128.2, 131.8, 134.5, 138.9, 140.9, 142.8,
143.2, 164.6 ppm. HRMS (ESI): calcd for C18H15N2OS2 [MH]þ
339.0625; found 339.0622.
4.2.14. 3-(Methylthio)-1-(naphthalen-2-yl)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6c) and 3-methoxy-1-(naphthalen-2-yl)-5H-di-
benzo[d,f][1,3]diazepin-6(7H)-one (7c). It was prepared from the
reaction of indolin-2-one 5 (0.146 g, 1.1 mmol) and 4-(methylthio)-
6-(naphthalen-2-yl)-2-oxo-2H-pyran-3-carbonitrile 3c (0.293 g,
1 mmol) and isolated as described earlier, yield 252 mg, (66%) as
a mixture of 6c and 7c in ratio of 86:14. 6c: 1H NMR (300 MHz,
4.2.10. N-(4-(3-(Methylthio)-6-oxo-6,7-dihydro-5H-dibenzo[d,f][1,3]
diazepin-1-yl)phenyl)acetamide (6j). It was prepared from the re-
action of indolin-2-one 5 (0.146 g, 1.1 mmol), N-(4-(3-cyano-4-
(methylthio)-2-oxo-2H-pyran-6-yl)phenyl)acetamide 3j (0.3 g,
1 mmol) and potassium tert-butoxide (0.24 g, 2.1 mmol) as a white
amorphous solid, yield, 206 mg, (53%). Mp 287e290 ꢀC. Rf (50%
EtOAc/Hexane) 0.37. nmax (KBr) 3508, 3394, 3319, 3246, 1689, 1594,
DMSO-d6):
d
¼2.49 (s, 3H, SCH3), 6.49e6.53 (m, 2H, ArH), 7.07e7.10
1534, 1375, 1232, 1164 cmꢁ1. 1H NMR (400 MHz, DMSO-d6):
d
¼1.96
(m, 5H, ArH), 7.45e7.48 (t, J¼4.0 Hz, 2H, ArH), 7.65 (m, 1H, ArH),
7.77 (d, J¼6.0 Hz, 3H, ArH), 8.79 (s, 1H, NHCO), 8.94 (s, 1H, CONH),
HRMS (ESI): calcd for C24H19N2OS [MH]þ 383.1218; found 383.1214.
(s, 3H, COCH3), 2.46 (s, 3H, SCH3), 6.47e6.65 (m, 3H, ArH),
6.90e7.02 (m, 5H, ArH), 7.38 (d, J¼7.0 Hz, 2H, ArH), 8.67 (s, 1H,
NHCO), 8.84 (s, 1H, CONH) ppm. HRMS (ESI): calcd for C22H20N3O2S
[MH]þ 390.1276; found 390.1275.
7c: 1H NMR (300 MHz, DMSO-d6):
d
¼3.81 (s, 3H, OCH3), 6.49e6.53
(m, 2H, ArH), 7.07e7.10 (m, 5H, ArH), 7.45e7.48 (t, J¼4.0 Hz, 2H,
ArH), 7.65 (m, 1H, ArH), 7.77 (d, J¼6.0 Hz, 3H, ArH), 8.75 (s, 1H,
NHCO), 8.89 (s, 1H, CONH) ppm. HRMS (ESI): calcd for C24H19N2O2
[MH]þ 367.1446; found 367.1436.
4.2.11. 11-Bromo-3-(methylthio)-1-phenyl-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6k). It was isolated from the reaction of 5-
bromoindolin-2-one (0.212 g, 1 mmol), 4-(methylthio)-2-oxo-6-
phenyl-2H-pyran-3-carbonitrile 3a (0.243 g, 1 mmol) and potas-
sium tert-butoxide (0.24 g, 2.1 mmol) as a white amorphous pow-
der, yield,160 mg, (39%). Mp 265e270 ꢀC. Rf (30% EtOAc/Hexane)
0.32. nmax (KBr) 3399, 3238, 3125, 2923, 2850, 1705, 1591, 1556,
4.2.15. 1-(4-Chlorophenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6d) and 1-(4-chlorophenyl)-3-methoxy-5H-di-
benzo[d,f][1,3]diazepin-6(7H)-one (7d). It was isolated from the
reaction of indolin-2-one
5 (0.146 g, 1.1 mmol) and 6-(4-
1373, 1231 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
d
¼2.47 (s, 3H,
chlorophenyl)-4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile 3d
(0.278 g, 1 mmol) as described earlier, yield 169 mg, (46%) as
a mixture of 6d and 7d in ratio 65:35. 6d: 1H NMR (400 MHz,
SCH3), 6.56 (m, 1H, ArH), 6.96e7.03 (m, 5H, ArH), 7.22e7.25 (m, 4H,
ArH), 8.83 (s, 1H, NHCO), 9.01 (s, 1H, CONH) ppm. 13C NMR
(100 MHz, DMSO-d6):
d
¼14.3, 114.5, 116.4, 122.4, 122.8, 123.0, 127.2,
DMSO-d6):
d
¼2.52 (s, 3H, SCH3), 6.51e6.78 (m, 2H, ArH), 6.98e7.11
128.4, 129.6, 130.2, 130.6, 134.8, 139.7, 140.1, 140.6, 142.2, 142.9,
164.3 ppm. HRMS (ESI): calcd for C20H16BrN2OS [MH]þ 411.0166;
found 411.0165.
(m, 6H, ArH), 7.30 (d, J¼8.0 Hz, 2H, ArH), 8.76 (s, 1H, NHCO), 8.91 (s,
1H, CONH) ppm. HRMS (ESI): calcd for C20H16ClN2OS [MH]þ
367.0671; found 367.0671. 7d: 1H NMR (400 MHz, DMSO-d6):
d
¼3.80 (s, 3H, SCH3), 6.51e6.78 (m, 2H, ArH), 6.98e7.11 (m, 6H,
4.2.12. 3-(Methylthio)-1-phenyl-5H-dibenzo[d,f][1,3]diazepin-6(7H)-
one (6a) and 3-methoxy-1-phenyl-5H-dibenzo[d,f][1,3]diazepin-6(7H)-
one (7a). A mixture of indolin-2-one 5 (0.146 g, 1.1 mmol) and 4-
(methylthio)-2-oxo-6-phenyl-2H-pyran-3-carbonitrile 3a (0.243 g,
1 mmol) in freshly prepared solution of sodium methoxide by dis-
solving sodium (48 mg, 2.1 mmol) in methanol (10 mL) was refluxed
for 10 h. The excess of solvent was removed and viscous mass was
poured onto the crushed ice with vigorous stirring and neutralized
with 10% aq HCl. The precipitate obtained was filtered, washed with
water and dried. The dried crude product was purified on silica gel
column using hexane/chloroform (60:40) as eluent, yield 173 mg
(52%). The product isolated was distinguished by 1H NMR as a mix-
ture of 6a and 7a in ratio of 69:31. 6a: 1H NMR (400 MHz, DMSO-d6):
ArH), 7.30 (d, J¼8.0 Hz, 2H, ArH), 8.72 (s, 1H, NHCO), 8.86 (s, 1H,
CONH) ppm. HRMS (ESI): calcd for C20H16ClN2O2 [MH]þ 351.0900;
found 351.0905.
4.2.16. 1-(4-Chlorophenyl)-3-(piperidin-1-yl)-5H-dibenzo[d,f][1,3]di-
azepin-6(7H)-one (9a). A mixture of 5 (0.146 g, 1.1 mmol) and 6-(4-
chlorophenyl)-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles
4d (0.316 g, 1.0 mmol) in a freshly prepared solution of Na (48 mg,
2.1 mmol) in dry methanol (10 mL) was refluxed for 4 h. The excess
methanol was removed under reduced pressure and thereafter,
poured onto the crushed ice with vigorous stirring. The reaction
mixture was neutralized with aq HCl and the precipitate obtained
was filtered, dried and purified on silica gel column using hexane/
chloroform (60:40) as eluent to get a white powder yield, 222 mg
(55%). Mp 280e282 ꢀC. Rf (30% EtOAc/Hexane) 0.65. nmax (KBr)
d
¼2.48 (s, 3H, SCH3), 6.49e6.70 (m, 2H, ArH), 6.95e7.07 (m, 5H,
ArH), 7.20 (s, 3H, ArH), 8.74 (s, 1H, NHCO), 8.89 (s, 1H, CONH) ppm.
HRMS (ESI): calcd for C20H17N2OS [MH]þ 333.1061; found 333.1055.
3457, 3420, 3243, 3022, 2934, 1696, 1607, 1216; cmꢁ1
.
1H NMR
7a: 1H NMR (400 MHz, DMSO-d6):
d¼3.78 (s, 3H, OCH3), 6.49e6.70
(400 MHz, DMSO-d6):
d¼1.54e1.55 (m, 6H, piperidinyleCH2), 3.18
(m, 2H, ArH), 6.95e7.07 (m, 5H, ArH), 7.20 (s, 3H, ArH), 8.71 (s, 1H,
NHCO), 8.59 (s, 1H, CONH) ppm. HRMS (ESI): calcd for C20H17N2O2
[MH]þ 317.1290; found 317.1282.
(bs, 4H, piperidinyleCH2), 6.40e6.41 (m, 1H, ArH), 6.61e6.91 (m,
2H, ArH), 6.67 (m, 1H, ArH), 6.99e7.00 (m, 4H, ArH), 7.21e7.23 (m,
2H, ArH), 8.47 (s, 1H, NHCO), 8.76 (s, 1H, CONH) ppm. 13C NMR
(100 MHz, DMSO-d6):
d
¼24.1, 25.0, 48.7, 106.0, 106.2, 113.6, 116.7,
4.2.13. 1-(4-Bromophenyl)-3-(methylthio)-5H-dibenzo[d,f][1,3]dia-
zepin-6(7H)-one (6b) and 1-(4-bromophenyl)-3-methoxy-5H-di-
benzo[d,f][1,3]diazepin-6(7H)-one (7b). It was prepared from the
120.9, 122.5, 126.8, 128.1, 128.9, 131.4, 132.4, 140.4, 140.8, 141.2,
143.7, 150.7, 164.6. HRMS (ESI): calcd for C24H23ClN3O [MH]þ
404.1529; found 404.1528.
reaction of indolin-2-one
5 (0.146 g, 1.1 mmol) and 6-(4-
bromophenyl)-4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile 3b
(0.322 g, 1 mmol) and isolated as described earlier, yield, 197 mg,
(48%) as a mixture of 6b and 7b in ratio 9:1. 6b: 1H NMR (400 MHz,
4.2.17. 1-Phenyl-3-(piperidin-1-yl)-5H-dibenzo[d,f][1,3]diazepin-
6(7H)-one (9b). It was obtained by refluxing indolin-2-one 5
(0.146 g, 1.1 mmol) and 2-oxo-6-phenyl-4-(piperidin-1-yl)-2H-py-
ran-3-carbonitrile 4a (0.28 g,1 mmol) in a freshly prepared solution
DMSO-d6):
d¼2.48 (s, 3H, SCH3), 6.50e6.52 (m, 1H, ArH), 6.67e6.77

4864
S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
of sodium (48 mg, 2.1 mmol) in methanol (10 mL) for 6 h and
worked up as described earlier, yield 215 mg, (58%) as a colourless
powder. Mp 272e275 ꢀC. Rf (30% EtOAc/Hexane) 0.69. nmax (KBr)
3452, 3240, 2931, 1687, 1222 cmꢁ1. 1H NMR (400 MHz, DMSO-d6):
180e181 ꢀC. Rf (30% EtOAc/Hexane) 0.46. nmax (KBr) 3129, 2228,
1678, 1217 cmꢁ1 1H NMR (400 MHz, DMSO-d6):
.
d¼2.23 (s, 3H,
SCH3), 4.75 (s, 2H, CH2), 5.19 (s,1H, ArH), 5.89 (d, J¼8.0 Hz,1H, ArH),
6.59 (t, J¼8.8 Hz, 1H, ArH), 6.78 (d, J¼7.2 Hz, 1H, ArH), 7.08 (t,
J¼8.8 Hz, 1H, ArH), 7.33 (m, 4H, ArH), 10.7 (s, 1H, NHCO) ppm. 13C
d
¼1.58 (bs, 6H, piperidinyleCH2), 3.20 (bs, 4H, piperidinyleCH2),
6.43e6.56 (m, 3H, ArH), 6.64e6.70 (m, 4H, ArH), 6.99e7.07 (m, 3H,
ArH), 7.19 (d, J¼6.0 Hz, 2H, ArH), 8.48 (s, 1H, NHCO), 8.77 (s, 1H,
NMR (100 MHz, DMSO-d6):
d
¼14.7, 39.0, 89.9, 109.6, 116.0, 116.2,
116.8, 120.9, 122.1, 122.7, 126.6, 129.4, 129.5, 129.6, 141.1, 148.5,
163.5, 168.4; HRMS (ESI): calcd for C20H16FN2OS [MH]þ 351.0967;
found 351.0966.
CONH) ppm. 13C NMR (100 MHz, DMSO-d6)
d
¼24.0, 25.0, 48.8,
105.8, 113.8, 116.9, 120.8, 122.3, 126.5, 126.6, 128.1, 129.2, 129.6,
132.4, 140.4, 142.2, 142.3, 143.6, 150.8, 164.9 ppm. HRMS (ESI): calcd
for C24H24N3O [MH]þ 370.1919; found 370.1917.
4.3. X-ray crystallography
4.2.18. 1-(4-Bromophenyl)-3-(piperidin-1-yl)-5H-dibenzo[d,f][1,3]di-
azepin-6(7H)-one (9c). It was obtained from the reaction of indo-
lin-2-one 5 (0.146 g, 1.1 mmol) and 6-(4-bromophenyl)-2-oxo-4-
(piperidin-1-yl)-2H-pyran-3-carbonitrile 4b (0.36 g, 1 mmol) in
a freshly prepared solution of sodium (48 mg, 2.1 mmol) in meth-
anol (10 mL) and worked up as described earlier, yield (228 mg,
51%) as a white amorphous powder. Mp >300 ꢀC. Rf (30% EtOAc/
Intensity data for all the three compounds were collected at
298(2) K on a Sapphire2-CCD, OXFORD diffractometer system
equipped with graphite monochromated Mo
K
a
radiation
ꢀ
l¼0.71073 A. The final unit cell determination, scaling of the data,
and corrections for Lorentz and polarization effects were performed
with CrysAlis RED.31 The structures were solved by direct methods
(SHELXS-97)32 and refined by a full-matrix least-squares procedure
based on F2.33 All the calculations were carried out using WinGX
system Ver-1.64.34 All non-hydrogen atoms were refined aniso-
tropically; hydrogen atoms were located at calculated positions and
refined using a riding model with isotropic thermal parameters
fixed at 1.2 times the Ueq value of the appropriate carrier atom.
Hexane) 0.51. nmax (KBr) 3475, 2930, 1639, 1220 cmꢁ1
.
1H NMR
(400 MHz, DMSO-d6)
d¼1.57e1.58 (bs 6H, piperidinyleCH2), 3.21
(bs, 4H, piperidinyleCH2), 6.43 (d, J¼8.04 Hz, 1H, ArH), 6.63e6.70
(m, 3H, ArH), 7.01e7.02 (m, 4H, ArH), 7.38e7.42 (m, 2H, ArH), 8.49
(s, 1H, NHCO), 8.78 (s, 1H, CONH). HRMS (ESI): calcd for
C24H23BrN3O [MH]þ 448.1024; found 448.1025.
4.3.1. Crystal data for 6a. C42H38N4O3S3, formula mass 742.94,
monoclinic space group P121/C1, a¼19.5001(9), b¼8.4923(3),
4.2.19. 1-(4-Methoxyphenyl)-3-(piperidin-1-yl)-5H-dibenzo[d,f][1,3]
diazepin-6(7H)-one (9d). It was prepared by refluxing a mixture of
indolin-2-one 5 (0.146 g, 1.1 mmol) and 6-(4-methoxyphenyl)-2-
3
ꢀ
¼92.088(3)ꢀ,
V¼3788.5(3)
A ,
Z¼4,
ꢀ
c¼22.8927(8)
A,
b
dcalcd¼1.303 mg mꢁ3, linear absorption coefficient 0.241 mmꢁ1
,
oxo-4-(piperidin-1-yl)-2H-pyran-3-carbonitrile 4f (0.31
g,
F(000)¼1560, crystal size 0.29ꢂ0.20ꢂ0.18 mm, reflections col-
lected 37,984, independent reflections 9203 [Rint¼0.0258], Final
1 mmol) in a freshly prepared solution of sodium (48 mg,
2.1 mmol) in methanol (10 mL) and worked up as described ear-
lier, yield (188 mg, 47%) as a colourless powder. Mp >300 ꢀC. Rf
(30% EtOAc/Hexane) 0.48. nmax (KBr) 3440, 3249, 2925, 1691, 1607,
indices [I>2
s
(I)] R1¼0.0797 wR2¼0.1919,
R indices (all data)
R1¼0.1048, wR2¼0.2065, gof 1.107, Largest difference peak and hole
ꢀꢁ3
0.564 and ꢁ0.706 e A
.
1243 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
d
¼1.59 (bs, 6H, piper-
idinyleCH2), 3.18 (bs, 4H, piperidinyleCH2), 3.69 (s, 3H, ArH),
6.49e6.77 (m, 6H, ArH), 7.00e7.01 (m, 4H, ArH), 8.43 (s, 1H,
NHCO), 8.73 (s, 1H, CONH); HRMS (ESI): calcd for C25H26N3O2
[MH]þ 400.20.25; found 400.2024.
4.3.2. Crystal data for 6e. C24H25N3O2S, formula mass 419.53, tri-
ꢀ
clinic space group P-1, a¼8.704(5), b¼11.427(5), c¼12.210(5) A,
3
ꢀ
ꢀ
a
¼92.425(5),
b
¼103.656(5),
g
¼109.446(5) , V¼1103.0(9) A , Z¼2,
dcalcd¼1.263 mg mꢁ3, linear absorption coefficient 0.172 mmꢁ1
,
F(000)¼444, crystal size 0.40ꢂ0.25ꢂ0.15 mm, reflections collected
12,648, independent reflections 7268 [Rint¼0.0652], Final indices
4.2.20. (3Z,5Z)-3-(Methylthio)-5-(2-oxoindolin-3-ylidene)-5-
phenylpent-3-enenitrile (11a). A mixture of indolin-2-one
5
[I>2
s
(I)] R1¼0.0994 wR2¼0.2473, R indices (all data) R1¼0.1361,
(0.146 g, 1.1 mmol), 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-3-
carbonitrile 3a (0.243 g, 1.0 mmol) and sodium hydride
(2.1 mmol, 60%) in dry THF (10 mL) was refluxed for 5 h. Excess of
THF was removed under reduced pressure and thereafter poured
onto the crushed ice with vigorous stirring. The aqueous solution
was neutralized with dil aq HCl. The precipitate obtained was fil-
tered, dried and purified as pale-yellow crystalline solid from silica
gel column chromatography using hexane/chloroform (70:30) as
eluent. Yield,193 mg, (58%). Mp 192e193 ꢀC. Rf (30% EtOAc/Hexane)
0.54. nmax (KBr) 3174, 2962, 2205, 1689, 1613, 1561, 1220 cmꢁ1. 1H
wR2¼0.2908, gof 1.053, Largest difference peak and hole 0.454
ꢀꢁ3
and ꢁ0.912 e A
.
4.3.3. Crystal data for 11a. C20H16N2OS, formula mass 332.42, tri-
ꢀ
clinic space group P-1, a¼8.356(2), b¼8.672(3), c¼13.307(4) A,
3
ꢀ
a
¼93.81(3),
b
¼92.30(2),
g
¼114.36(3)ꢀ, V¼874.1(5) A , Z¼2,
dcalcd¼1.263 mg mꢁ3, linear absorption coefficient 0.193 mmꢁ1
,
F(000)¼348, crystal size 0.30ꢂ0.20ꢂ0.15 mm, reflections collected
7120, independent reflections 3916 [Rint¼0.0632], Final indices
[I>2
s
(I)] R1¼0.0586 wR2¼0.1590, R indices (all data) R1¼0.0989,
NMR (400 MHz, DMSO-d6):
d
¼2.23 (s, 3H, SCH3), 4.77 (s, 2H, CH2),
wR2¼0.1928, gof 1.112, Largest difference peak and hole 0.209
ꢀꢁ3
5.18 (s, 1H, CH), 5.92 (m, 1H, ArH), 6.53 (m, 1H, ArH), 6.79 (m, 1H,
ArH), 7.08 (m, 1H, ArH), 7.29 (m, 2H, ArH), 7.48 (m, 3H, ArH), 10.70
and ꢁ0.273 e A
.
CCDC 897838 (for 6a), 897839 (for 6e) and 897837 (for 11a)
contains supplementary crystallographic data. These data can be
obtained free of charge from the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
(s, 1H, NHCO) ppm. 13C NMR (100 MHz, DMSO-d6):
d¼14.6, 39.0,
89.8, 109.5, 116.8, 120.7, 122.2, 122.8, 126.2, 127.0, 128.8, 129.0, 129.3,
138.3, 141.1, 149.5, 163.6, 168.5 ppm. HRMS (ESI): calcd for
C20H16N2OS [MH]þ 333.1061; found 333.1061.
4.4. Computational methods
4.2.21. (3Z,5Z)-5-(4-Fluorophenyl)-3-(methylthio)-5-(2-oxoindolin-
3-ylidene)pent-3-enenitrile (11b). It was obtained by refluxing
In order to understand the stability of various non-covalent
interactions some quantum chemical calculations were carried
out. All the calculations were performed using the Gaussian 03
package.35 Initial geometries of the non-covalently bonded dimers
were taken from the respective crystal structures. All calculations
a
mixture of indolin-2-one 5 (0.146 g, 1.1 mmol), 6-(4-
fluorophenyl)-4-(methylthio)-2-oxo-2H-pyran-3-carbonitrile 3k
(0.261 g, 1 mmol) and sodium hydride (2.1 mmol, 60%) in THF
(10 mL) for 5 h as a yellow powder, yield, 194 mg, (55%). Mp

S. Kumar et al. / Tetrahedron 69 (2013) 4857e4865
4865
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DEdimer¼Edimerꢁ(2ꢂEmo-
nomer). Emonomer was calculated by optimizing a single molecule at
the same level of theory. The intermolecular interaction strengths
are significantly weaker than either ionic or covalent bonding,
therefore it was essential to do basis set superposition error (BSSE)
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energies have been reported after BSSE correction.37
Acknowledgements
Sandeep is thankful to DST, New Delhi, India for the Award of
INSPIRE Fellowship [IF10379] and Authors are also grateful to So-
phisticated Analytical Instrumental Facility, CDRI, Lucknow for
spectral analysis of the compounds reported herein.
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