Gold catalyzed synthesis of tetrahydropyrimidines and octahydroquinazolines under ball milling conditions and evaluation of anticonvulsant potency

Article abstract of DOI:10.24820/ark.5550190.p010.372

A fast, mechanochemical and solvent-free synthesis of substituted tetrahydropyrimidines and octahydroquinazolines under Au(III)-catalysis has been developed. The practical feasibility, eco-friendliness and operational simplicity of this chemistry is exemplified by ball milling three components such as formaldehyde, amines and 2-butynedioates/dimedone in a shaker mill for as little as five minutes, thus avoiding the requirement of undesirable solvents and long reaction times. Moreover, this protocol furnishes the target compounds in high yields without any side products and in some cases offers products with excellent regioselectivity. Out of the 26 compounds screened for anticonvulsant potency, 11 compounds exhibited comparable activity against a standard drug.

Full text of DOI:10.24820/ark.5550190.p010.372

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Organic Chemistry
Arkivoc 2018, part iii, 90-101
Gold catalyzed synthesis of tetrahydropyrimidines and octahydroquinazolines
under ball milling conditions and evaluation of anticonvulsant potency
M. Vadivelu,a A. A. Raheem,b S. Sugirdha,a G. Bhaskar,c K. Karthikeyan,*a and C. Praveen*b
aDepartment of Chemistry, B. S. Abdur Rahman Crescent University, Chennai-600 048, Tamil Nadu, India
bFunctional Materials Division, Central Electrochemical Research Institute (CSIR Laboratory), Karaikudi-630003,
Tamil Nadu, India
cDepartment of Chemistry, Government Polytechnic College, Aranthangi–614 616, Tamil Nadu, India
Email: karthiclri@gmail.com; chandrasekar.praveen@gmail.com
Dedicated with respect to Dr. P. T. Perumal for his 35 years of contribution to synthetic organic chemistry
Received 10-23-2017
Accepted 12-16-2017
Published on line 12-21-2017
Abstract
A
fast, mechanochemical and solvent-free synthesis of substituted tetrahydropyrimidines and
octahydroquinazolines under Au(III)-catalysis has been developed. The practical feasibility, eco-friendliness
and operational simplicity of this chemistry is exemplified by ball milling three components such as
formaldehyde, amines and 2-butynedioates/dimedone in a shaker mill for as little as five minutes, thus
avoiding the requirement of undesirable solvents and long reaction times. Moreover, this protocol furnishes
the target compounds in high yields without any side products and in some cases offers products with
excellent regioselectivity. Out of the 26 compounds screened for anticonvulsant potency, 11 compounds
exhibited comparable activity against a standard drug.
COOR
COOR
2 HCHO
ROOC
ROOC
R1
.
NaAuCl4 2H2O (1 mol%)
N
+
ball milling (agate)
400 rpm, 5 min
N
R1
R1NH2
2
O
.
O
O
NaAuCl4 2H2O (1 mol%)
R2
ball-milling
400 rpm
R2NH2 2a-2i
N
R1NH2
+
O
R1
N
R1
30 min
2 HCHO
N
H
ball-milling, 400 rpm, 30 min
Keywords: Mechanochemistry, gold catalysis, multicomponent reaction, tetrahydropyrimidines,
octahydroquinazolines, anticonvulsant
DOI: https://doi.org/10.24820/ark.5550190.p010.372
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Introduction
Green chemistry has become one of the powerful tools for organic chemists to increase molecular complexity
from simple substrates in a convenient manner.1 In particular, circumvention of solvents in chemical processes
or the replacement of hazardous organic solvents with environmentally benign solvents has received
paramount importance in the context of a green economy. Within the purview of sustainable development,
the current areas of interest are to synthesize complex molecular frameworks by multicomponent reactions,2
solvent-free organic transformations,3 and water-assisted organic reactions.4 Especially, multicomponent
reactions under one-pot conditions have substantial advantage over multistep synthesis, because of i) the
construction of complex molecules from readily available raw materials, ii) operational simplicity, iii) reduction
of intermediate isolation as well as purification steps and iv) minimization of cost/time/waste.5
Pyrimidines and their analogues represent an important class of nitrogen heterocycles which are found as
key structural constituent in various bio-active natural compounds and clinical drugs.6-8 Specifically,
tetrahydropyrimidines have attracted much attention, because of their interesting and unique therapeutic
properties such as muscarinic agonist activity,9 anti-inflammatory activity,10 and antiviral activity.11 It is also
noteworthy are the magnetic properties of pyrimidinyl nitronyl nitroxide radicals.12 However, the reported
methodologies have not been entirely satisfactory because of the associated drawbacks such as low yields,
long reaction time and cumbersome experimental processes.13 Some of the previous multicomponent
syntheses of tetrahydropyrimidines involve ZrOCl2 catalysis in water,14 refluxing in DMF,15 and iodine catalysis
under reflux.16 Though these strategies are synthetically attractive, their utility is limited only to the synthesis
of tetrahydropyrimidines and no octahydroquinazoline syntheses were demonstrated. As part of our research
interests on new synthetic methodologies for pharmacologically important molecules,17-32 we have
demonstrated the catalytic application of gold for the construction of various structurally challenging carbo-
and heterocycles.33-48 In order to circumvent the aforementioned limitations linked with the synthesis of
dihydropyrimidines, coupled with our research interests in gold catalysis, we have now investigated the
synthesis of both tetrahydropyrimidines and octahydroquinazolines under the catalytic influence of gold.
Towards this end, we herein report an improved methodology for the solvent-free synthesis of
tetrahydrohydropyrimidine / octahydroquinazoline derivatives under mechanochemical conditions in
presence of Au(III) as catalyst.
Results and Discussion
Synthesis of tetrahydropyrimidine derivatives
.
Based on our previous experience with NaAuCl4 2H2O,34 which can serve as both an oxophilic as well as a
carbophilic catalyst, we initiated our studies using this particular catalyst. We aimed at solvent-free conditions,
however, in order to drive the reaction between the substrates, the reactants have to be close enough, which
we thought could be achieved by mechanical chemistry.49 In this connection, we initially evaluated the
reaction between a mixture of diethyl but-2-ynedioate 1a (1.0 mmoL), aniline 2a (2.0 mmoL), formaldehyde
.
(2.0 mmoL) and NaAuCl4 2H2O (1 mol%) ball-milled at 400 rpm for 5 minutes (Scheme 1).
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Scheme 1. Prototype reaction under ball-milling.
We were pleased to find that the reaction proceeds smoothly under this conditions and the starting
materials were consumed completely as evidenced by TLC. Purification of the crude residue by column
chromatography afforded the product 3a in excellent yield (92%). The structure of the isolated product 3a was
assigned based on IR, NMR and mass spectral data. The IR spectrum of 3a exhibits a strong stretching peak at
1740 cm-1 corresponding to ester groups. In the 1H NMR spectrum of 3a, two triplets at δ 0.98 (t, J 6.8 Hz, 3H),
1.27 (t, J 6.8 Hz, 3H) and two quartets at δ 4.02 (q, J 6.8 Hz, 2H), 4.18 (q, J 6.8 Hz, 2H) were assigned to CH3-
and CH2- of the two ester groups respectively. The two singlets at δ 4.26 (s, 2H), 4.90 (s, 2H) were attributed to
the two CH2- groups in the tetrahydropyrimidine ring. In the 13C NMR spectrum, the peaks at δ 164.0 and
165.7 ppm were assigned to the two carbonyl groups. Finally the structure was confirmed by mass
spectrometry, which showed an ion at m/z = 381 corresponding to [M+1]+. Delighted with the initial positive
.
result, we next assessed the role of catalyst in this reaction. In a blank reaction without using NaAuCl4 2H2O
and even after one hour, only a minimal quantity of starting materials was consumed, thus supporting the
.
catalytic role of NaAuCl4 2H2O in this transformation. Satisfied with the initial excellent result, we chose these
conditions, which are practical to perform and also environmentally friendly, for the synthesis of structurally
different tetrahydropyrimidines. When these reaction conditions were applied to other substrates, the desired
products 3a-g were obtained in good to excellent chemical yields (Scheme 2). Significantly, our chemistry is
tolerant towards aliphatic, benzylic and aromatic amines. However, we used only formaldehyde for our
reactions because of its high reactivity and because attempted use of other aldehydes possessing alkyl or aryl
groups, afforded complex products. All reactions went to completion within five minutes and the results are
summarized in Table 1.
Table 1 Tetrahydropyrimidines 3a-g prepared under ball-milling conditions
Entry
R (1)
R1 (2)
Ph (2a)
Bn (2b)
Product (3)a Yield (%)b
1
2
3
4
5
6
7
Et (1a)
Et (1a)
Me (1b)
Me (1b)
Et (1a)
3a
3b
3c
3d
3e
3f
92
95
87
90
85
93
85
t-Bu (2c)
Bn (2b)
o-ClC6H4 (2d)
Me (1b) p-BrC6H4 (2e)
Et (1a) t-Bu (2c)
3g
aProducts were characterized by IR, 1H NMR, 13C NMR and mass spectrometry
bIsolated yield of products after column chromatography
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Scheme 2. Synthesis of 1,3-symmetrically substituted tetrahydropyrimidines.
In an attempt to glean information about the regiochemistry of our methodology, unsymmetrical alkynes
such as 1c and 1d were subjected to the standardized conditions (Scheme 3). According with our expectations,
only products 3h and 3i were obtained, whilst the corresponding regioisomers 3hʹ and 3iʹ were not obtained.
This can be attributed to the partial depletion of electron density at the β-carbon by COOEt group, which
directs the attack of nucleophilic amine towards the β-carbon of gold-activated alkyne I selectively to form the
enaminium intermediate II for further transformation.
Scheme 3. Regioselective synthesis of tetrahydropyrimidines from unsymmetrical alkynes.
Having established a satisfactory protocol for the synthesis of 1,3-symmetrically substituted
tetrahydropyrimidines, we next directed our studies towards the synthesis of 1,3-unsymmetrically substituted
tetrahydropyrimidines using our reaction conditions. Towards this end, when we used differently substituted
amines such as aniline and benzylamine at the same time, obtaining a mixture of two regioisomeric products
as evidenced by NMR analysis of the crude product. In order to obtain a particular single product exclusively,
we added the specified amines in a sequential manner. Thus, from the sequential addition of aniline 2a (amine
1) with 1a, followed by addition with benzylamine 2b (amine 2), we obtained the desired product 5a as the
sole product (Scheme 4). We believe that 2a initially undergoes typical gold-activated hydroamination with 1a
to form intermediate 4, which then subsequently reacts with 2b and formaldehyde to generate the product
5a.
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Scheme 4. Rationale for the formation of tetrahydropyrimidine 5a from two different amines.
1
The structure of the product was assigned based on NMR and mass spectral data. In the H NMR spectrum
of compound 5a, the two triplets at δ 1.02 (t, J 6.9 Hz, 3H), 1.22 (t, J 7.6 Hz, 3H) and two quartets at δ 4.05 (q, J
6.9 Hz, 2H), 4.13 (q, J 7.6 Hz, 2H) was assigned to -CH3 and -CH2 of two ester groups respectively. The three
singlets at δ 3.71 (s, 2H), 3.81 (s, 2H) and 4.33 (s 2H) were attributed to two -CH2 groups in the pyrimidine ring
13
and one benzylic -CH2 group. In the C NMR spectrum, the peaks at δ 164.2 and 166.3 ppm were assigned to
the two ester carbonyl carbons. Finally, the structure of the compound was unequivocally confirmed by a
mass spectrum which showed m/z = 395 (M+1)+. Pleased with these results, we incorporated differently
substituted amines in a sequential manner for the synthesis of a range of 1,3-unsymmetrical
tetrahydropyrimidines (Scheme 5). As depicted in Table 2, the sequences afforded good to excellent yields of
products in about five minutes tolerating both alkyl and aromatic amines. However, the yields of the products
was slightly diminished for ortho-substituted and bulky amines (entries 4 and 5), perhaps due to a steric effect.
Scheme 5. Synthesis of 1,3-unsymmetrically substituted tetrahydropyrimidines .
Table 2 Tetrahydropyrimidines 5a-e prepared under ball-milling conditions
Entry
R1 (2)
R2 (2)
Product
(5)a
5a
Yield (%)b
1
2
3
4
5
Ph (2a)
Bn (2b)
Ph (2a)
Bn (2b)
Ph (2a)
t-Bu (2c)
91
94
92
76
79
5b
5c
5d
5e
Ph (2a)
o-Cl-C6H4 (2d)
Ph (2a)
o-ClC6H4 (2d)
aProducts were characterized by IR, 1H NMR, 13C NMR and mass spectrometry
bIsolated yields of products after column chromatography
Synthesis of octahydroquinazoline derivatives
Up to this point, we have described the reactivity of acetylenic precursors (1a-1d) for the synthesis of
tetrahydropyrimidines. A further extension of this methodology was envisaged in the one-pot synthesis of
octahydroquinazoline derivatives under our reaction conditions. Such compounds are little known in
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literature, hence their biological properties remain largely unexplored. We began with a control experiment
treating dimedone 6 (1.0 mmoL) with aniline 2a (1.0 mmoL) to form the enaminone intermediate 7 under ball-
milling for 30 minutes without added catalyst (Scheme 6). To this enaminone intermediate was added another
.
mole of aniline and formaldehyde (2.0 mmoL) in presence of NaAuCl4 2H2O (1 mol%) and ball-milling
continued for the next 30 minutes. To our delight, the targeted product 1,2,3,4,7,8-hexahydro-7,7-dimethyl-
1,3-diphenylquinazolin-5(6H)-one 8a was isolated in 90% yield. However, the second transformation was not
.
effected in the absence of the gold catalyst. These findings revealed that the catalytic action of NaAuCl4 2H2O
is required only for the second step and not for enaminone formation. Alternatively, the same reaction was
carried out in a one-flask operation without isolating the enaminone by the addition of aniline (2.0 equiv) and
formaldehyde (2.0 equiv) leading to the product 8a with almost the same yield (91%). The structure of the
1
compound 8a was assigned based on the NMR and mass spectral data. In the H NMR spectrum, a sharp
singlet at δ 0.93 (6H, s) corresponds to the two methyl groups on the carbocyclic ring and two singlets at δ
2.00 (2H, s) and 2.22 (2H, s) correspond to the ring methylene groups. The methylene group protons adjacent
to the nitrogen were represented by two singlets at δ 4.31 (2H, s) and 4.94 (2H, s). The 13C NMR shows a peak
at δ 28.4 for two methyl carbons and a less intense peak at δ 32.7 represents the quaternary carbon carrying
two methyl groups. The peaks at δ 41.1 and 50.1 corresponds to two methylene carbons of the carbocycle.
The peaks at δ 45.6 and 70.2 corresponds to the two methylene carbons in the pyrimidine ring. The double
bond carbons shows two signals one at δ 104.9 and another in the aromatic region. The carbonyl carbon signal
was at δ 194.2. Finally the structural characterization was conclusively assigned by mass spectrometry, which
showed m/z = 333 [M+1]+.
Scheme 6. Synthesis of 5-oxo-octahydroquinazoline 8a through two steps.
By utilizing our reaction conditions, both 1,3-symmetrical and 1,3-unsymmetrical 5-oxo-
octahydroquinazolines could be produced from a variety of amines and dimedone (Scheme 7). Analysis of the
results as depicted in Table 3 reveals that there is an obvious steric effect of substituents on the reactivity as
evidenced by reduced yields in case of substrates possessing ortho substitution (entries 4 to 7). Another
distinguishing feature is the overall reaction time of one hour which is higher than for the synthesis of the
tetrahydropyrimidines (compare Tables 1 & 2 with Table 3). We also examined the same transformation under
o
conventional heating and compared with our mechanochemical process. Under neat conditions at 80 C the
yields of products from all substrates were found to be slightly lower than by the mechanochemical method,
vindicating the effectiveness of the mechanochemical method over conventional heating for these
transformations.
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Scheme 7. Synthesis of 5-oxo-octahydroquinazoline derivatives 8a-k.
Table 3. 5-Oxo-octahydroquinazolines 8a-k prepared under ball-milling conditions
Entry
R1 (2)
R2 (2)
Product
(8)a
8a
Yield (%)b,c
Yield (%)b,d
1
2
3
4
5
6
7
8
9
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
91
85
88
74
73
75
72
87
81
86
89
75
68
69
56
49
44
45
66
58
75
73
p-BrC6H4 (2e)
p-MeOC6H4 (2f)
o,p-Me2C6H3 (2g)
o-MeOC6H4 (2h)
o-ClC6H4 (2d)
o,p-Cl2C6H3 (2g)
Bn (2b)
t-Bu (2c)
p-BrC6H4 (2e)
p-MeOC6H4 (2f)
8b
8c
8d
8e
8f
8g
8h
8i
10
11
p-Br-Ph (2e)
p-MeO-Ph (2f)
8j
8k
aProducts were characterized by IR, 1H NMR, 13C NMR and mass spectrometry
bIsolated yields of products after column chromatography
cYield from mechanochemical synthesis
dYield from conventional heating under neat conditions at 80 oC for 1 h
Evaluation of anticonvulsant potency
In pursuance of our on-going projects on bioactive carbo-/heterocycles, an attempt was made to evaluate the
anticonvulsant properties of the compounds against Maximal ElectroShock (MES) induced seizure through in
vivo rodent models.50 Results of the anticonvulsant activity with reference drug phenytoin are provided in
Table 1 of ESI†. It was found that all compounds were active at a dose level of 15 mg/kg, which is indicative of
their ability to prevent convulsion spread. The MES-convulsions are divided into three phases such as (a) tonic
flexion, (b) tonic extensor and (c) clonic convulsions. The time (s) spent by the animal in each phase of the
convulsions was noted. A substance is shown to possess anticonvulsant property if it reduces or abolishes the
extensor phase of MES-convulsion. Analysis of Table 1 revealed that eleven compounds from the
octahydroquinazoline series (8a-k) showed anticonvulsant activity with extensor values lower than that of the
standard. 1,3-Unsymmetrically substituted tetrahydropyrimidines (5a-e) emerged as the second most active
series with extensor values slightly less than the standard. However, 1,3-symmetrically substituted pyrimidines
(3a-g) showed poor activity among the screened series. We rationalized that the symmetric nature of the
amine residues in 3a-g might be the reason for the much reduced activity compared to their unsymmetric
counterparts 5a-e. Interestingly, compounds 3h and 3i possessing Me and Ph groups respectively at the C-6
position enhanced the anticonvulsant potency, exhibiting extensor time closer to that of phenytoin. This result
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also suggested that a lipophilic alkyl or aryl substitution at C-6 instead of a polar COOR group enhances the
activity. Attempts to understand the SAR of the molecules began with the peripheral ring of the molecules.
Generally, tetrahydropyrimidine fused to a cyclohexenone ring, the so called 5-oxo-octahydroquinazolines 8a-
k increased the potency greatly compared to unfused tetahydropyrimidines 3a-i and 5a-c, suggesting the
necessity of a less polar cyclohexyl ring compared to more polar COOR group. Among the most active series,
compounds with hydrophobic groups such as p-MeOC6H4 and t-Bu (8c and 8i) emerged as the most active over
all the other compounds. Replacement of p-MeOC6H4 8c or t-Bu 8i by other hydrophobic groups such as o,p-
Me2 8d or Bn groups showed only a tiny decrease in activity.
Conclusions
In summary, we have developed an efficient and practical Au(III)-catalyzed multicomponent reaction for the
synthesis of tetrahydropyrimidines and octahydroquinazolines by a mechanochemical approach. Low catalytic
loading, short reaction time, good to excellent chemical yields and no solvent used are the beneficial
advantages of our methodology. Also, this method is a clean and safe process, and can be used to generate a
wide array of structurally interesting hybrid heterocycles. Synthetic elaboration of our methodology to the
preparation of clinical drugs as well as molecular docking studies of the most active compounds is actively
underway in our laboratory.
Experimental Section
General. All commercially available solvents and reagents were used without further purification. Melting
points were determined in capillary tubes and are uncorrected. Mechanochemical reactions were
accomplished in a Fritsch ‘‘Pulverisette 7 classic line’’ (Fritsch GmbH, Idar-Oberstein, Germany) planetary ball
mill using 45 mL grinding beakers (agate) and milling balls (6 X 15 mm; agate). All reaction vessels were
cleaned with aqua regia prior to use to avoid any contamination or memory effects. Infrared (IR) spectra were
1
recorded on a Perkin-Elmer FTIR spectrophotometer as neat samples. H and 13C NMR spectra were obtained
in CDCl3 on a Bruker spectrometer at 500 and 125 MHz, respectively. Proton chemical shifts (δ) are relative to
tetramethylsilane (TMS, δ = 0.00) as internal standard and expressed in parts per million. Spin multiplicities
are given as s (singlet), d (doublet), t (triplet) and m (multiplet). Coupling constants (J) are given in Hertz. Mass
spectra were recorded on a PE-SCIEX API 300 mass spectrometer. HRMS data were collected on a Maxis 10138
mass spectrometer. Elemental analyses were recorded using a ThermoFinnigan FLASH EA 1112CHN analyzer.
All the compounds gave C, H and N analyses within ±0.5% of the theoretical values. Analytical TLC was
performed on precoated plastic sheets of silica gel G/UV-254 of 0.2 mm thickness (Macherey-Nagel, Germany)
using analytical grade solvents and visualized with iodine spray (10% (w/w) I2 in silica gel) or UV light (λ = 254
and 365 nm).
Representative experimental procedure for the synthesis of tetrahydropyrimidines (3b). The grinding
beakers (45 mL; agate) were equipped with 6 milling balls of the same material (d = 15 mm). Diethyl but-2-
.
ynedioate 1a (1.0 mmoL), benzylamine 2b (2.0 mmoL), NaAuCl4 2H2O (1.0 mol%) and formaldehyde (2.0
mmoL) were added in the given order. Ball-milling was carried out at 400 rpm for 5 min. The residue was
dissolved in EtOAc (20 mL) and the extracts washed with H2O (3
×
15 mL). The organic layer was dried over
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anhydrous Na2SO4 and the solvent removed under reduced pressure to afford the crude product, which was
purified by flash column chromatography using EtOAc/PE (10:90) as eluent to obtain tetrahydropyrimidine 3b
as a viscous yellow liquid in 95% yield. IR (neat) νmax: 3350, 2979, 1731, 1684, 1585, 1448, 1366, 1279, 1261,
1
1111, 1036, 1042, 745 cm-1; H NMR (500 MHz, CDCl3): δ 1.22 (t, 3H, J 7.6 Hz), 1.30 (t, 3H, J 6.8 Hz), 3.57 (s,
2H), 3.61 (s, 2H), 3.83 (s, 2H) , 4.12 (q, 2H, J 6.8 Hz,), 4.17 (s, 2H), 4.35 (q, 2H, J 7.6 Hz), 7.16-7.31 (m, 10H); 13C
NMR (125 MHz, CDCl3): δ 13.9, 14.5, 48.6, 54.1, 57.1, 59.7, 62.1, 66.1, 92.5, 127.3, 128.0, 128.1, 128.3, 128.4,
128.7, 136.4, 138.1, 148.2, 165.2, 166.4.; MS: m/z = 409 (M+H)+. Anal. Calcd for C24H28N2O4: C, 70.57; H, 6.91;
N, 6.86%. Found: C, 70.62; H, 6.95; N, 6.78%.
Representative experimental procedure for the synthesis of 5-oxo-octahydroquinazoline (8c). The grinding
beakers (45 mL; agate) were equipped with 6 milling balls of the same material (d = 15 mm). A mixture of
.
dimedone 6 (1.0 mmoL), aniline 2a (1.0 mmoL) and NaAuCl4 2H2O (1.0 mol%) was ball-milled for 30 min at 400
rpm. Then to this mixture was added p-anisidine 2f (1.0 mmoL), formaldehyde (2.0 mmoL) and the mixture
ball-milled for a further 30 min at 400 rpm. Afterwards, the residue was dissolved in EtOAc (20 mL) and the
solution washed with H2O (3 × 15 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was
removed under reduced pressure to give crude product, which was purified by flash column chromatography
using EtOAc/PE (20:80) as eluent to obtain 5-oxo-octahydroquinazoline 8c as a yellow viscous oil; IR (neat)
1
νmax: 3454, 3049, 2949, 1568, 1505, 1399, 1289, 1252, 1036, 829, 701 cm-1; H NMR (500 MHz, CDCl3): δ 0.92
(6H, s), 1.98 (2H, s), 2.21 (2H, s), 3.74 (3H, s), 4.23 (2H, s), 4.84 (2H, s), 6.78 (2H, d, J 9.2 Hz), 6.92 (4H, t, J 6.1
Hz), 7.27 (1H, t, J 7.7 Hz), 7.34 (2H, t, J 7.7 Hz); 13C NMR (125 MHz, CDCl3): δ 28.4, 32.7, 41.1, 46.0, 50.1, 55.5,
71.4, 104.5, 114.5, 119.7, 127.4, 127.5, 129.7, 142.3, 142.8, 154.3, 157.5, 194.2; MS m/z = 363 (M+H)+; Anal.
Calcd for C23H26N2O2: C, 76.21; H, 7.23; N 7.73%; Found: C, 76.14; H, 7.28; N, 7.80%.
Acknowledgements
The work has been financially supported by the fast track grant for young scientists from the Science and
Engineering Research Board (SERB), India, which is greatly acknowledged by authors K. K. and C. P. for grants
SB/FT/CS-033/2013 and SERB/F/5666/2015-16 respectively.
Supplementary Material
Supplementary data contains complete characterization data, NMR spectra of representative compounds and
anticonvulsant results of all compounds.
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