Synthesis of diverse fused tetracyclic thiazepine-chalcone derivatives by claisen-schmidt condensation reaction and their antimicrobial activity

Article abstract of DOI:10.14233/ajchem.2020.22867

To develop antimicrobial agent, a series of thiazepine-chalcones was synthesized by Claisen-Schmidt condensation between the couplings of aryl ketone in three steps protocol and different aromatic aldehydes under strong base catalyst at room temperature. The characterization of final products were carried out by IR, ¹H & ¹³C NMR and elemental analysis. The synthesized compounds were also evaluated for their antibacterial and antifungal activities using specific Gram positive and Gram-negative bacterial strains using cup plate method.

Full text of DOI:10.14233/ajchem.2020.22867

Asian Journal of Chemistry; Vol. 32, No. 11 (2020), 2860-2864
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2020.22867
Synthesis of Diverse Fused Tetracyclic Thiazepine-Chalcone Derivatives by
Claisen-Schmidt Condensation Reaction and their Antimicrobial Activity
1,*,
1,
2,
JAYANTI B. HIRANI
, MAYANK K. PANDYA
and SURESH B. KORADIYA
1B.R.C.C. Laboratory, Department of Chemistry, School of Science, R K University, Rajkot-360020, India
2Department of Chemistry, Shree M. & N. Virani Science College, Rajkot-360005, India
*Corresponding author: E-mail: jayant.hirani@yahoo.co.in
Received: 19 June 2020;
Accepted: 14 August 2020;
Published online: 28 October 2020;
AJC-20109
To develop antimicrobial agent, a series of thiazepine-chalcones was synthesized by Claisen-Schmidt condensation between the
couplings of aryl ketone in three steps protocol and different aromatic aldehydes under strong base catalyst at room temperature. The
characterization of final products were carried out by IR, 1H & 13C NMR and elemental analysis. The synthesized compounds were also
evaluated for their antibacterial and antifungal activities using specific Gram positive and Gram-negative bacterial strains using cup plate
method.
Keywords: Claisen-Schmidt condensation, Tetracyclic, Thiazepine, Antimicrobial activity.
sulfur and nitrogen heteroatoms, due to which they possess a
broad spectrum of pharmacological activities [20]. The distin-
ctive feature of the thiazepine core is that it is active against
different families of targets, making them interesting hetero-
cyclic ring systems [21]. Various active benzothiazepines are
found in current lead discovery process and first molecule of
1,5-benzothiazepine core was found in cardiovascular action
(diltiazem and clentiazem) [22]. Quetiapine, a derivative of
benzothiazepine, is an antipsychotic drug used for the treat-
ment of schizophrenia and bipolar disorder [23,24].
The synthesis of new derivatives possessing antibacterial
activity has considerable attention owing to the continued
increase in bacterial resistance [25]. It is reported that benzo-
thiazepine and substituted benzothiazepine-2-one exhibited
strong antibacterial activity along with unsaturated enone systems
[26]. In present communication, we report a reaction of modified
acetophenone with the different aromatic aldehydes to form novel
chalcone scaffolds (7a-j). The structures of the various synthe-
sized compounds were assigned based on IR, 1H & 13C NMR
spectral data and elemental analysis. These compounds were
also screened for their antimicrobial activity against some
Gram-positive and Gram-negative strains to find the best anti-
bacterial and antifungal agents.
INTRODUCTION
Chalcones are well known intermediates for synthesizing
various heterocyclic compounds which comprise the aromatic
ketone that forms the central core of many important biological
compounds, which are to have various biological activities such
as antimicrobial [1], anti-inflammatory [2], locomotor [3],
antiplatelet [4], antimalarial [5], anticancer [6], antiviral [7],
antibacterial, antifungal [8], antiproliferative [9], anti-
Alzheimers [10], TACE and MMP inhibitors [11], inhibition
of leukotriene CysLT [12], antihypertensive [13], antimicrobial
[14], antioxidant [15], anticonvulsant [16], etc. To date numerous
works are reported based on the chemistry of chalcones and is
still an attraction among the organic chemists, due to open-
chain model and the feature of skeletal modification to produce
a new class of organic compounds [17].
In short, chalcones are an innovative class of compounds
with significant therapeutic potential against various diseases
particularly when it coupled with other macro/microcyclic systems
[18]. One of the important class of derivatives is benzothiaze-
pines, which shows various biological functions when attached
to chalcone precursor [19]. Benzothiazepines are important
structural scaffolds of seven-membered heterocycles and contain
This is an open access journal, and articles are distributed under the terms of the Attribution 4.0 International (CC BY 4.0) License. This
license lets others distribute, remix, tweak, and build upon your work, even commercially, as long as they credit the author for the original
creation. You must give appropriate credit, provide a link to the license, and indicate if changes were made.

Vol. 32, No. 11 (2020)
Synthesis of Diverse Fused Tetracyclic Thiazepine-Chalcone Derivatives 2861
mol) in methanol (30 mL) were taken in a round-bottom flask
with 30 mL 20% NaOH solution. The reaction mixture was
EXPERIMENTAL
The required chemicals and solvents for the synthesis were
purchased from Merck Ltd. and SD fine chemicals, India. The
agar medium and PDA medium were purchased from HI media
Laboratories Ltd., Mumbai, India. Most of the reactions were
carried out by standard techniques for the exclusion moisture.
The open-end capillary method was used to determine the melting
points of the synthesized derivatives and are uncorrected. Thin
layer chromatography (TLC) was used for reaction monitoring
using ethyl acetate:n-hexane as a mobile phase and visualized
in UV light (254 and 365 nm). IR spectra of all compounds were
recorded on a Shimadzu, Japan IR-435 spectrophotometer using
ATR technique. The 1H NMR (400 MHz) and 13C NMR (101
MHz) spectra were recorded on Bruker AVANCE II Spectro-
meter using DMSO-d6 as solvent and TMS as the internal
reference. Mass spectra were recorded on a Jeol-JMSD 300
mass spectrometer at 70ev. Elemental analysis was carried out
by a Perkin-Elmer 2400 CHN analyzer.
stirred for 24-26 h at ambient temperature. After completion
of the reaction, the mixture was poured into crushed ice. The
separated solid was filtered, dried and recrystallized from ethanol
(Scheme-I).
OH
Cl
O
N
N
a
S
2
S
H2N
1
3
b
O
O
HN
N
O
HN
c
N
S
S
4
S
R
6a-j
5
Synthesis of 11-chlorodibenzo[b,f][1,4]thiazepine (2):
Dibenzo[b,f][1,4]thiazepin-11-ol (0.01 mol) (1) and 60 mL
POCl3 were taken in a dry round bottom flask. The reaction
mixture was refluxed with constant stirring at 70 ºC for about
3 h. After completion of the reaction, it was cooled to room
temperature and poured into crushed ice. The solid separated
was filtered and dried using a vacuum dryer. The dried product
was recrystallized using methanol to afford analytically pure
products. The progress of the reaction was monitored by TLC
using n-hexane:ethyl acetate (6:4) as a mobile phase.
d
O
R
HN
S
N
S
7a-j
Reaction condition: (a) POCl3, reflux, 3 h, (b) pyridine, heat 161 oC, 4 h,
(c) sulphur, I2, heat 161 °C, 30 min, (d) 20% NaOH, RT-stirring, 24-26 h
Scheme-I: Synthetic path for the synthesis of title compounds (7a-j)
Synthesis of 1-(4-(dibenzo[b,f][1,4]thiazepin-11-ylamino)-
phenyl)ethanone (4): 11-Chlorodibenzo[b,f][1,4]thiazepine
(0.01 mol) (2) was taken in 70 mL of pyridine in two-necked
round bottom flask. 1-(4-Aminophenyl)ethanone (0.015 mol)
(3) was added into the reaction mixture over for 10 min. It
was heated at 116 ºC and continuously stirred for 4 h. After
completion of the reaction, it was cooled to 28 ºC and poured
onto crushed ice water under stirring conditions. The obtained
solid was filtered, dried in rota vapor to get 1-[4-(dibenzo[b,f]-
[1,4]thiazepine-11-ylamino)phenyl]ethanone (4). The comple-
tion of the reaction was monitored by TLC using ethyl acetate:
benzene (7:3) as a mobile phase.
Synthesis of 1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]-
heptalen-6-yl)ethanone (5): In a 100 mL round bottom flask,
mixture of 1-(4-(dibenzo[b,f][1,4]thiazepin-11-ylamino)phenyl)-
ethanone (0.01 mol) (4) and sulphur (0.02 mol) were charged
in the presence of catalytic amount of iodine.The reaction mixture
was heated in an oil bath at 161 ºC with constant stirring for
30 min. After the completion of the reaction, it was poured
into crushed ice and stirred well for 15 min. The solid separated
was filtered and washed with cold water. The product obtained
was dried and recrystallized from methanol. The purity of the
synthesized compound and the extent of completion of reaction
were monitored using TLC with mobile phase ethyl acetate:
n-hexane (3:7).
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-phenylprop-2-en-1-one (7a): Yield: 69.35%; m.p.:
201 ºC; IR (νmax, cm-1): 3226 (N-H str.), 2975 (C-H str.), 1641
(C=O str.), 1736 (C=C str.), 1534, 1452, 1319 (ring skeleton),
1441 (C-H bend.), 1342 (N-H bend.), 1345 (C-N str.), 1254
(C-S str.); 1H NMR (400 MHz, DMSO-d6) δ ppm: 6.949-6.981
(1H, m, Ar-H), 7.011-7.031 (1H, d,Ar-H), 7.125-7.252 (2H, m,
Ar-H), 7.357-7.142 (3H, m, Ar-H), 7.462-7.551 (8H, m, Ar-H),
7.853-7.834 (1H, d, =CH), 8.253-8.232 (1H, d, =CH), 9.625
(1H, s, -NH); 13C NMR (101 MHz, DMSO-d6) δ ppm: 191.85,
145.51, 144.21, 144.21, 143.22, 140.85, 138.21, 135.84, 133.78,
132.02, 131.95, 130.12, 128.77, 128.77, 127.52, 125.11, 125.11,
124.80, 127.36, 127.36, 125.32, 123.52, 121.02, 117.58, 125.37,
104.95; MS: m/z 462 (M+); Elemental analysis calcd. (found)
% for C28H18N2OS2: C, 72.70 (72.65); H, 3.92 (3.95); N, 6.06
(6.11); O, 3.46 (3.40); S, 13.86 (13.83).
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(2-methoxyphenyl)prop-2-en-1-one (7b): Yield:
71.42%; m.p.: 218 ºC; IR (νmax, cm-1): 3238 (N-H str.), 2960
(C-H str.), 1648 (C=O str.), 1616 (C=C str.), 1554, 1440, 1328
(ring skeleton), 1416 (C-H bend.), 1322 (N-H bend.), 1325
(C-N str.), 1258 (C-S str.), 1152 (C-O str.); 1H NMR (400 MHz,
DMSO-d6) δ ppm: 3.819 (3H, s, -OCH3), 6.973-7.031 (2H, d,
Ar-H), 7.156-7.286 (2H, m, Ar-H), 7.411-7.396 (3H, m, Ar-H),
7.501-7.590 (7H, m, Ar-H), 7.862-7.841 (1H, d, =CH), 8.258-
8.239 (1H, d, =CH), 9.632 (1H, s, -NH); 13C NMR (101 MHz,
Synthesis of 1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]-
heptalen-6-yl)-3-arylprop-2-en-1-one (7a-j): Intermediate
(5) and different substituted aromatic aldehydes (6a-j) (0.01

2862 Hirani et al.
Asian J. Chem.
DMSO-d6) δ ppm: 193.25, 168.21, 154.45, 151.78, 151.78,
148.12, 146.08, 140.85, 138.26, 135.80, 134.10, 133.42, 132.90,
131.20, 130.42, 128.12, 127.20, 126.85, 123.51, 121.86, 120.12,
118.41, 117.20, 115.65, 114.62, 110.51, 46.81; MS: m/z 492
(M+); Elemental analysis calcd. (found) % for C29H20N2O2S2:
C, 70.71 (70.74); H, 4.09 (4.06); N, 5.69 (5.72); O, 6.50 (6.48);
S, 13.02 (13.05).
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(2-nitrophenyl)prop-2-en-1-one (7f):Yield: 77.57%;
m.p.: 252 ºC; IR (νmax, cm-1): 3223 (N-H str.), 2971 (C-H str.),
1649 (C=O str.), 1632 (C=C str.), 1545 (C-NO2 str.), 1527, 1438,
1317 (ring skeleton), 1403 (C-H bend.), 1346 (N-H bend.),
1324 (C-N str.), 1242 (C-S str.); 1H NMR (400 MHz, DMSO-
d6) δ ppm: 6.583-6.610 (2H, m, Ar-H), 6.702-6.786 (2H, m,
Ar-H), 6.965-7.182 (2H, m, Ar-H), 7.226-7.367 (2H, m, Ar-H),
7.471-7.956 (6H, m, Ar-H), 7.846-7.827 (1H, d, =CH), 8.236-
8.217 (1H, d, =CH), 9.635 (1H, s, -NH);13C NMR (101 MHz,
DMSO-d6) δ ppm: 192.12, 178.12, 175.10, 169.45, 166.74,
161.12, 157.89, 155.41, 152.63, 140.86, 138.52, 137.25, 135.81,
134.63, 134.63, 132.85, 131.45, 130.41, 130.41, 129.45, 127.582,
123.09, 120.58, 118.34, 118.34, 109.80; MS: m/z 507 (M+);
Elemental analysis calcd. (found) % for C28H17N3O3S2: C, 66.26
(66.24); H, 3.38 (3.41); N, 8.28 (8.25); O, 9.46 (9.49); S, 12.63
(12.58).
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(3-nitrophenyl)prop-2-en-1-one (7g):Yield: 82.63%;
m.p.: 259 ºC; IR (νmax, cm-1): 3234 (N-H str.), 2978 (C-H str.),
1645 (C=O str.), 1667 (C=C str.), 1584 (C-NO2 str.), 1552, 1458,
1378 (ring skeleton), 1456 (C-H bend.), 1320 (N-H bend.),
1388 (C-N str.), 1253 (C-S str.); 1H NMR (400 MHz, DMSO-d6)
δ ppm: 6.612-6.628 (1H, m, Ar-H), 6.755-6.776 (1H, d, Ar-H),
6.821-7.220 (3H, m, Ar-H), 7.301-7.378 (2H, m, Ar-H), 7.568-
7.978 (7H, m, Ar-H), 7.768-7.786 (1H, d, =CH), 8.178-8.20
(1H, d, =CH), 9.618 (1H, s, -NH); 13C NMR (101 MHz, DMSO-
d6) δ ppm: 191.12, 188.47, 181.45, 179.12, 179.12, 168.42,
166.52, 160.74, 152.56, 150.45, 147.20, 144.41, 140.245, 136.75,
135.45, 135.45, 133.82, 132.20, 130.89, 128.45, 125.78, 124.23,
123.45, 122.81, 121.81, 107.72; MS: m/z 507 (M+); Elemental
analysis calcd. (found) % for C28H17N3O3S2: C, 66.26 (66.29);
H, 3.38 (3.44); N, 8.28 (8.30); O, 9.46 (9.41); S, 12.63 (12.67).
1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(4-nitrophenyl)prop-2-en-1-one (7h):Yield: 88.68%;
m.p.: 272 ºC; IR (νmax, cm-1): 3232 (N-H str.), 2951 (C-H str.),
1643 (C=O str.), 1687 (C=C str.), 1582 (C-NO2 str.), 1584, 1444,
1325 (ring skeleton), 1462 (C-H bend.), 1359 (N-H bend.),
1321 (C-N str.), 1288 (C-S str.); 1H NMR (400 MHz, DMSO-d6)
δ ppm: 6.948-6.988 (1H, m, Ar-H), 7.017-7.038 (1H, d, Ar-H),
7.149-7.269 (2H, m, Ar-H), 7.355-7.455 (3H, m, Ar-H), 7.438-
7.589 (7H, m, Ar-H), 7.856-7.837 (1H, d, =CH), 8.255-8.235
(1H, d, =CH), 9.631 (1H, s, -NH);13C NMR (101 MHz, DMSO-
d6) δ ppm: 194.12, 182.72, 179.35, 159.63, 159.63, 156.74,
154.85, 153.08, 149.52, 148.58, 146.95, 143.56, 138.42, 136.89,
136.89, 136.89, 134.20, 130.07, 129.31, 129.31, 126.02, 125.98,
123.29, 120.20, 117.95, 104.42; MS: m/z 507 (M+); Elemental
analysis calcd. (found) % for C28H17N3O3S2: C, 66.26 (66.28);
H, 3.38 (3.39); N, 8.28 (8.23); O, 9.46 (9.41); S, 12.63 (12.60).
1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]heptalen-6-
yl)-3-(4-aminophenyl)prop-2-en-1-one (7i): Yield: 72.77%;
m.p.: 193 ºC; IR (νmax, cm-1): 3296 (N-H str.), 2968 (C-H str.),
1643 (C=O str.), 1624 (C=C str.), 1526, 1445, 1369 (ring
skeleton), 1406 (C-H bend.), 1342 (N-H bend.), 1365 (C-N str.),
1254 (C-S str.); 1H NMR (400 MHz, DMSO-d6) δ ppm: 4.635-
4.218 (2H, s, -NH2), 6.552-6.638 (1H, m, Ar-H), 7.021-7.266
(3H, m, Ar-H), 7.352-7.524 (4H, m, Ar-H), 7.561-7.769 (6H,
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-6-
yl)-3-(4-methoxyphenyl)prop-2-en-1-one (7c):Yield: 83.01%;
m.p.: 215 ºC; IR (νmax, cm-1): 3232 (N-H str.), 2928 (C-H str.),
1634 (C=O str.), 1665 (C=C str.), 1588, 1441, 1324 (ring skeleton),
1414 (C-H bend.), 1384 (N-H bend.), 1324 (C-N str.), 1253
(C-S str.), 1178 (C-O str.); 1H NMR (400 MHz, DMSO-d6) δ
ppm: 3.736 (3H, s, -OCH3), 6.854-6.912 (2H, d, Ar-H), 7.041-
7.152 (2H, m,Ar-H), 7.378-7.297 (3H, m,Ar-H), 7.497-7.478
(7H, m, Ar-H), 7.858-7.836 (1H, d, =CH), 8.241-8.262 (1H,
d, =CH), 9.621 (1H, s, -NH); 13C NMR (101 MHz, DMSO-d6)
δ ppm: 191.12, 176.45, 154.10, 151.35, 150.74, 149.14, 146.82,
141.20, 138.23, 135.59, 133.18, 132.20, 130.85, 130.85, 128.23,
128.23, 127.23, 125.95, 123.21, 121.85, 120.98, 119.12, 117.86,
115.95, 112.23, 111.95, 49.49; MS: m/z 492 (M+); Elemental
analysis calcd. (found) % for C29H20N2O2S2: C, 70.71 (70.68);
H, 4.09 (4.11); N, 5.69 (5.64); O, 6.50 (6.56); S, 13.02 (13.07).
1-(9H-4,15-Dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one (7d):Yield:
76.69%; m.p.: 234 ºC; IR (νmax, cm-1): 3246 (N-H str.), 2978
(C-H str.), 1635 (C=O str.), 1627 (C=C str.), 1561, 1416, 1394
(ring skeleton), 1418 (C-H bend.), 1360 (N-H bend.), 1367
(C-N str.), 1256 (C-S str.), 1132 (C-O str.); 1H NMR (400 MHz,
DMSO-d6) δ ppm: 3.839-3.825 (6H, s, -OCH3), 6.952-6.993
(1H, m, Ar-H), 7.021-7.042 (1H, d, Ar-H), 7.146-7.266 (2H,
m, Ar-H), 7.369-7.432 (3H, m, Ar-H), 7.483-7.586 (6H, m,
Ar-H), 7.856-7.837 (1H, d, =CH), 8.255-8.235 (1H, d, =CH),
9.626 (1H, s, -NH); 13C NMR (101 MHz, DMSO-d6) δ ppm:
195.45, 184.12, 171.56, 162.58, 160.28, 160.28, 156.20, 151.52,
148.85, 146.76, 143.89, 140.86, 139.20, 137.81, 138.81, 135.20,
132.95, 130.85, 129.85, 127.21, 126.95, 124.45, 122.20, 118.36,
116.51, 113.89, 51.23, 51.23; MS: m/z 522 (M+); Elemental
analysis calcd. (found) % for C30H22N2O3S2: C, 68.94 (68.89);
H, 4.24 (4.18); N, 5.36 (5.38); O, 9.18 (9.21); S, 12.27 (12.29).
1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]heptalen-6-
yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (7e): Yield:
85.75%; m.p.: 249 ºC; IR (νmax, cm-1): 3225 (N-H str.), 2976
(C-H str.), 1642 (C=O str.), 1640 (C=C str.), 1524, 1458, 1328
(ring skeleton), 1412 (C-H bend.), 1348 (N-H bend.), 1347
(C-N str.), 1172 (C-O str.); 1H NMR (400 MHz, DMSO-d6) δ
ppm: 3.781 (9H, s, -OCH3), 6.941-6.972 (1H, m,Ar-H), 7.009-
7.021 (1H, d, Ar-H), 7.128-7.249 (2H, m, Ar-H), 7.331-7.406
(2H, m, Ar-H), 7.471-7.558 (6H, m, Ar-H), 7.851-7.829 (1H,
d, =CH), 8.249-8.228 (1H, d, =CH), 9.626 (1H, s, -NH); 13C NMR
(101 MHz, DMSO-d6) δ ppm: 194.25, 184.45, 179.58, 175.20,
168.10, 165.25, 160.98, 159.14, 156.10, 148.85, 145.85, 144.89,
142.98, 139.42, 137.81, 134.74, 134.74, 130.89, 129.10, 127.96,
125.12, 124.56, 123.29, 120.85, 103.56, 103.56, 69.12, 48.21,
48.21; MS: m/z 552 (M+); Elemental analysis calcd. (found)
% for C31H24N2O4S2: C, 67.37 (67.33); H, 4.38 (4.41); N, 5.07
(5.11); O, 11.58 (11.54); S, 11.60 (11.57).

Vol. 32, No. 11 (2020)
Synthesis of Diverse Fused Tetracyclic Thiazepine-Chalcone Derivatives 2863
m, Ar-H), 7.902-7.884 (1H, d, =CH), 8.236-8.254 (1H, d,
=CH), 9.632 (1H, s, -NH); 13C NMR (101 MHz, DMSO-d6) δ
ppm: 191.85, 185.12, 181.85, 175.48, 175.48, 168.15, 165.71,
162.02, 159.43, 155.45, 151.32, 148.32, 141.81, 141.81, 135.26,
135.26, 131.58, 129.84, 127.52, 125.23, 123.58, 121.22, 120.89,
117.47, 102.85, 102.85; MS: m/z 477 (M+); Elemental analysis
calcd. (found) % for C28H19N3OS2: C, 70.41 (70.43); H, 4.01
(4.06); N, 8.80 (8.78); O, 3.35 (3.39); S, 13.43 (13.47).
1-(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]heptalen-
6-yl)-3-(p-tolyl)prop-2-en-1-one (7j): Yield: 73.35%; m.p.:
227 ºC; IR (νmax, cm-1): 3237 (N-H str.), 2969 (C-H str.), 1736
(C=O str.), 1617 (C=C str.), 1527, 1436, 1320 (ring skeleton),
1411 (C-H bend.), 1385 (N-H bend.), 1358 (C-N str.), 1251
(C-S str.); 1H NMR (400 MHz, DMSO-d6) δ ppm: 2.423 (3H, s,
-CH3), 6.732-6.856 (1H, m, Ar-H), 7.023-7.046 (1H, d, Ar-H),
7.152-7.278 (2H, m,Ar-H), 7.353-7.478 (3H, m, Ar-H), 7.520-
7.706 (7H, m, Ar-H), 7.850-7.832 (1H, d, =CH), 8.252-8.232
(1H, d, =CH), 9.626 (1H, s, -NH);13C NMR (101 MHz, DMSO-
d6) δ ppm: 193.25, 180.51, 177.69, 177.69, 175.25, 171.29,
165.28, 158.14, 156.85, 150.01, 148.21, 137.52, 134.09, 130.22,
130.22, 128.98, 128.98, 127.87, 127.56, 126.33, 123.50, 122.41,
120.45, 119.87, 118.89, 111.98, 12.31; MS: m/z 476 (M+);
Elemental analysis calcd. (found) % for C29H20N2OS2: C, 73.08
(73.10); H, 4.23 (4.19); N, 5.88 (5.91); O, 3.36 (3.39); S, 13.46
(13.51).
1-[4-(dibenzo[b,f][1,4]thiazepin-11-ylamino)phenyl]ethanone
in high yield (91%). Intermediate 5 was synthesized by solid-
phase synthesis of iodine catalyzed reaction with sulphur in
passable heating conditions. Solution-phase synthesis of 1-
(9H-4,15-dithia-9,10-diazatribenzo[b,ef,i]heptalen-6-yl)-3-
arylprop-2-en-1-one (7a-j) was carried out by heating under
reflux of intermediate novel acetophenone (5) with various
arylaldehydes (6a-j) in dry MeOH in the presence of 20%
NaOH solution.
The structure of synthesized compounds 7a-j was confir-
med on the basis of spectral data. The IR spectrum of comp-
ound 7a showed a strong adsorption band at ~3236 cm-1 due
to N-H stretching, secondary amine.Absorption band appeared
at ~2984 cm-1 due to stretching vibrations of aromatic hydrogen
and absorption band at ~1687 cm-1 due to stretching vibration
to >C=O group. Sharp absorption peak observed at ~1584 cm-1
in -C-NO2 group. The absorption band at ~1321, ~1253 cm-1
corresponding to C-N, C-S stretching, respectively. In 1H NMR,
an appearance of singlet peaks in compounds 7a-j showed a
characteristic value at δ = ~9.61 ppm due to the presence of
secondary amine group in fused cyclic ring. The presence of
=CH- linkage showed a doublet peak at ~8.25 ppm. Three
protons of Ar-(OCH3) displayed singlet at δ = ~3.78 ppm.
Remaining all aromatic protons appeared multiplet in the
region δ = ~6.49 to ~7.82 ppm. Remaining substituents protons
were in good agreement with theoretical values. In 13C NMR,
the characteristic value around δ = ~175 ppm showed the pres-
ence of >C=O group attached with an aromatic ring. The
aromatic ring carbon and heterocyclic ring carbons were in
decent covenants with the theoretical values. The mass spectrum
revealed a molecular ion peak in compounds 7a-j at m/z = 462
to 552 in mass spectra, molecular ion peak was in agreement
with proposed molecular weight and elemental analysis.
Antimicrobial evaluation: The screening result revealed
that compounds 7a-j showed a significant antimicrobial activities.
In particular, compound 7c only showed mild inhibitory action
on Bacillus megaterium. Compounds 7f and 7j also only showed
mild inhibitory action on Bacillus subtilis. Compound 7d has
shown significant activity on Bacillus megaterium, Bacillus
Antimicrobial evaluation: The synthesized compounds
(7a-j) were screened for their antimicrobial activity against
two Gram-positive bacteria viz., Bacillus megaterium, Bacillus
subtilis and two Gram-negative bacteria viz., Escherichia coli,
Enterobacter aerogenes by using cup plate method [27].
Similarly, the compounds were also tested for their antifungal
activity using potato-dextrose-agar (PDA) medium by the same
cup plate method against Aspergillus awamori.
RESULTS AND DISCUSSION
Claisen-Schmidt condensation reaction of novel aceto-
phenone synthesized using three-step procedures staring with
dibenzo[b,f][1,4]thiazepin-11-ol in POCl3 medium followed
by chloroamine coupling in pyridine as a base catalyst obtained
TABLE-1
in vitro RESULTS OF ANTIBACTERIAL SCREENING OF COMPOUNDS 7a-j
Gram-positive bacteria Gram-negative bacteria
Fungi
No.
R
Bacillus megaterium
Bacillus subtilis
Escherichia coli Enterobacter aerogenes Aspergillus awamori
ATCC 14581
ATCC 23857
ATCC 25922
ATCC 13048
ATCC 22342
H
2-OCH3
4-OCH3
18
17
20
21
18
17
19
16
18
12
23
22
20
–
17
13
16
19
14
18
14
12
15
18
18
20
19
–
16
20
24
21
19
16
14
17
15
19
18
21
22
–
20
18
16
17
15
18
11
14
18
16
20
19
21
–
19
20
18
17
22
23
13
11
14
18
–
7a
7b
7c
7d
7e
7f
7g
7h
7i
3,4-(OCH3)2
3,4,5-(OCH3)3
2-NO2
3-NO2
4-NO2
4-NH2
4-CH3
7j
Ampicillin
Chloramphenicol
Norfloxacin
Griseofulvin
–
–
21

2864 Hirani et al.
Asian J. Chem.
8. V. Ambrogi, G. Grandolini, L. Perioli, M. Ricci, C. Rossi and L.
Tuttobello, Eur. J. Med. Chem., 25, 403 (1990);
https://doi.org/10.1016/0223-5234(90)90003-L
9. L. Wu, X. Yang, Q. Peng and G. Sun, Eur. J. Med. Chem., 127, 599
(2017);
subtilis and Escherichia coli. Compounds 7b, 7c, 7d and 7j
have shown high potency, especially against Escherichia coli.
Compounds 7a, 7b, 7f and 7i showed mild inhibitory action
on Enterobacter aerogenes. All the organisms employed at a
concentration of 50 µg/mL showed considerable antibacterial
and antifungal activities and are comparable to that of standard
drugs.
https://doi.org/10.1016/j.ejmech.2017.01.021
10. S. Das, M.A. Laskar, S.D. Sarker, M.D. Choudhury, P.R. Choudhury,
A. Mitra, S. Jamil, S.M.A. Lathiff, S.A. Abdullah, N. Basar, L. Nahar
and A.D. Talukdar, Phytochem. Anal., 28, 324 (2017);
https://doi.org/10.1002/pca.2679
11. A. Zask, J. Kaplan, X. Du, G. MacEwan, V. Sandanayaka, N. Eudy, J.
Levin, G. Jin, J. Xu, T. Cummons, D. Barone, S. Ayral-Kaloustian and
J. Skotnicki, Bioorg. Med. Chem. Lett., 15, 1641 (2005);
https://doi.org/10.1016/j.bmcl.2005.01.053
12. F.C. Cheng, J.J. Feng, K.H. Chen, H. Imanishi, M. Fujishima, H.
Takekoshi, Y. Naoki and M. Shimoda, Phytother. Res., 24, 43 (2010);
https://doi.org/10.1002/ptr.2864
13. J.W. Skiles, J.T. Suh, B.E. Williams, P.R. Menard, J.N. Barton, B. Loev,
H. Jones, E.S. Neiss and A. Schwab, J. Med. Chem., 29, 784 (1986);
https://doi.org/10.1021/jm00155a032
Conclusion
In this work, the strategy for the synthesis of desired novel
chalcones indicated that 1-(9H-4,15-dithia-9,10-diazatribenzo-
[b,ef,i]heptalen-6-yl)-3-arylprop-2-en-1-one derivatives are
pharmacologically moderately potent. The structural modifi-
cations of the basic structure in derived compounds with electron
releasing groups such as methoxy and amine showed better anti-
bacterial activity. Compounds having nitro group exhibited
more antifungal activity. These results suggested that chalcone
derivatives have excellent scope for further development as
commercial antimicrobial agents.
14. R. Anisetti and M. Srinivas Reddy, J. Sulfur Chem., 33, 363 (2012);
https://doi.org/10.1080/17415993.2012.683432
15. J.A. Diaz, E. Montero, S. Vega,V. Darias, M.L. Tello and S.S.Abdallah,
Arch. Pharm., 327, 157 (1994);
https://doi.org/10.1002/ardp.19943270306
ACKNOWLEDGEMENTS
16. A.L. Banty, The Antimicrobial Susceptibility Test, Principle and
Practice, edited by Illus lea and Febiger; Philadelphia, USA, pp. 180
(1976).
17. A. Rammohan, J.S. Reddy, G. Sravya, C.N. Rao and G.V. Zyryanov,
Environ. Chem. Lett., 18, 433 (2020);
The authors are thankful to NFDD, Saurashtra University,
Rajkot, India for the spectral analysis.
CONFLICT OF INTEREST
https://doi.org/10.1007/s10311-019-00959-w
18. K.M. Kapadiya, K.M. Kavadia, P.A. Manvar and R.C. Khunt, Antiinfect.
Agents, 13, 129 (2015);
https://doi.org/10.2174/2211352513666150915235745
19. K.A. El-Bayouki, Org. Chem. Int., 2013, 210474 (2013);
https://doi.org/10.1155/2013/210474
The authors declare that there is no conflict of interests
regarding the publication of this article.
REFERENCES
20. A.V. Chate, R.S. Joshi, P.V. Badadhe, S.K. Dabhade and C.H. Gill,
Bull. Korean Chem. Soc., 32, 3887 (2011);
1. M. Kumar, K. Sharma, A.K. Fogla, K. Sharma and M. Rathore, Res.
Chem. Intermed., 39, 2555 (2013);
https://doi.org/10.1007/s11164-012-0782-8
2. Y.H. Kim, J. Kim, H. Park, H.P. Kim, Biol. Pharm. Bull., 30, 1450
(2007);
https://doi.org/10.5012/bkcs.2011.32.11.3887
21. P. Martins, J. Jesus, S. Santos, L.R. Raposo, C. Roma-Rodrigues, P.V.
Baptista and A.R. Fernandes, Molecules, 20, 16852 (2015);
https://doi.org/10.3390/molecules200916852
22. R. Kaur, R. Singh and K. Singh, Chem. Biol. Lett., 3, 18 (2016).
23. J.R. Scarff and D.A. Casey, Pharm. Ther., 36, 832 (2011).
24. M. Riedel, N. Müller, M. Strassnig, I. Spellmann, E. Severus and H.J.
Möller, Neuropsychiatr. Dis. Treat., 3, 219 (2007);
https://doi.org/10.2147/nedt.2007.3.2.219
25. I.E. Cock, M.J. Cheesman, A. Ilanko and B. Blonk, Pharmacogn. Rev.,
11, 57 (2017);
https://doi.org/10.4103/phrev.phrev_21_17
26. B.V. Kendre, M.G. Landge and S.R. Bhusare, Arab. J. Chem., 12, 2091
(2019);
https://doi.org/10.1248/bpb.30.1450
3. J. Higgs, C. Wasowski, A. Marcos, M. Jukic, C.H. Paván, S. Gobec, F.
de Tezanos Pinto, N. Colettis and M. Mardera, Heliyon, 5, e01376
(2019);
https://doi.org/10.1016/j.heliyon.2019.e01376
4. C.-N. Lin, H.-K. Hsieh, H.-H. Ko, M.-F. Hsu, H.-C. Lin, Y.-L. Chang,
M.-I. Chung, J.-J. Kang, J.-P. Wang and C.-M. Teng, Drug Dev. Res.,
53, 9 (2001);
https://doi.org/10.1002/ddr.1163
5. J. Syahri, E. Yuanita, B.A. Nurohmah, R. Armunanto and B. Purwono,
Asian Pac. J. Trop. Biomed., 7, 675 (2017);
https://doi.org/10.1016/j.arabjc.2015.01.007
https://doi.org/10.1016/j.apjtb.2017.07.004
27. H.W. Seeley, P.J. Vandemark and P.J. van Demark, Microbes in Action:
A Laboratory Manual of Microbiology, W.H. Freeman: New York, edn
4 (1991).
6. M.R. Gudisela, N. Srinivasu, C. Mulakayala, P. Bommu, M.B. Rao
and N. Mulakayala, Bioorg. Med. Chem. Lett., 27, 4140 (2017);
https://doi.org/10.1016/j.bmcl.2017.07.029
7. A.A. El-Emam, M.A. Massoud, E.R. El-Bendary and M.A. El-Sayed,
Bull. Korean Chem. Soc., 25, 991 (2004);
https://doi.org/10.5012/bkcs.2004.25.7.991