Synthesis and antimicrobial activity of 4-(10H-phenothiazin-2-yl)- pyrimidin-2(1H)-one/thione derivatives

Article abstract of DOI:10.1002/jhet.704

A series of chalcones 3a-d containing phenothiazine nucleus were prepared by Claisen-Schmidt condensation. The chalcones on treatment with urea, thiourea, phenyl urea, and phenyl thiourea in alcoholic KOH yielded compounds 4a-p, and the structures of these compounds were confirmed by spectral and elemental analyses. The newly synthesized compounds were evaluated for antimicrobial activity.

Full text of DOI:10.1002/jhet.704

1004
Synthesis and Antimicrobial Activity of 4-(10H-Phenothiazin-
Vol 49
2-yl)-pyrimidin-2(1H)-one/thione Derivatives
a
Tanaji N. Bansodea,b and Gangadhar A. Meshram
*
aDepartment of Chemistry, University of Mumbai, Vidyanagari, Kalina, Santacruz (East),
Mumbai 400 098, India
bDepartment of Chemistry, B.N.N.College, Bhiwandi, Thane (M.S.) 421 305, India
*
E-mail: meshramga@chem.mu.ac.in
Received April 12, 2010
DOI 10.1002/jhet.704
Published online 26 October 2012 in Wiley Online Library (wileyonlinelibrary.com).
A series of chalcones 3a–d containing phenothiazine nucleus were prepared by Claisen–Schmidt con-
densation. The chalcones on treatment with urea, thiourea, phenyl urea, and phenyl thiourea in alcoholic
KOH yielded compounds 4a–p, and the structures of these compounds were confirmed by spectral and
elemental analyses. The newly synthesized compounds were evaluated for antimicrobial activity.
J. Heterocyclic Chem., 49, 1004 (2012).
INTRODUCTION
gave above 90% yield. The cyclization of chalcones 3a–d
with urea, thiourea, pheyl urea, and phenyl thiourea under
basic condition led to the formation of new pyrimidine
derivatives 4a–p. The reaction sequences are outlined in
Scheme 1.
Heterocyclic compounds particularly five- or six-
membered ring compounds have occupied the first place
among various classes of organic compounds for their
diverse biological activities [1]. Pyrimidine rings have
received significant attention owing to their diverse
range of biological properties [2,3]. Pyrimidine deri-
vatives are of interest because of their pharmacological
properties including antibacterial [4], anticancer [5],
antitubercular [6], antifungal [7], antimalerial [8], anal-
gesic [9], antihypertensive [10], and anti-inflammatory
activity [11,12].
Phenothiazine and related compounds have shown
diverse biological activities including tranquilizers [13],
anti-inflammatory [14], antimalarial [15], antipsychotropic
[16], antimicrobial [17], antitubercular [18–20], antitumor
[21–23] antihistamine [24], and analgesic [25,26] proper-
ties. These observations prompted us to synthesize the
Phenothiazine derivatives containing pyrimidine ring and
evaluate their antimicrobial activities.
Formation of substituted (10H-phenothiazin-2-yl) pyri-
midin-2(1H)-one/thione derivatives (4) was confirmed on
1
the basis of elemental analysis, IR, H NMR, and mass.
Compounds 4 showed IR absorption bands in the re-
gions 3331–3360 cm−1 (NH Streching), 1576–1593 cm−1
(C==N streching), and 1463–1469 cm−1 (C==C pyrimi-
dine). The 1H NMR spectrum of compounds 4a–p showed
singlet at d 8.11–8.79 due phenothiazine NH proton. In
case of compounds, 4a–d and 4i–l showed additional
singlet at 8.02–8.08 due to pyrimidine NH protons. It
showed multiplets at 7.87–6.66 due to aromatic protons
and one singlet at d 5.68–5.36 due to pyrimidine ring
protons in all compounds. The 13C NMR spectrum of 4
showed signals at d 115.3–144.7 due to aromatic carbons
and at d 104.7–109.8, 157.1–181.4 due to pyrimidine
ring carbons. The physical data of compounds 4a–p are
recorded in Table 1.
RESULT AND DISCUSSION
CONCLUSIONS
Chalcones 3a–d were obtained by Claisen–Schmidt
reaction, that is, by treating 2-acetylphenothiazine with
methanolic KOH (40%) and various aldehydes 2a–d
In conclusion, we have described a mild, efficient, and
convienent method for the synthesis of new 6-(10H-
© 2012 HeteroCorporation

September 2012
Synthesis and Antimicrobial Activity of 6-(10H-Phenothiazin-2-yl)
Pyrimidin-2(1H)-one/thione Derivatives
1005
Scheme 1. Synthetic route of compounds 4a–p, R = H, OCH3, Cl, OH, R1 = C6H5, Z = O, S. Reaction reagents and conditions (i) 40% methanolic KOH,
reflux 70ꢀC, 2–3 h, 90%. (ii) Urea, phenyl urea, thiourea, and phenyl thiourea, reflux in methanolic KOH 70ꢀC, 3–4 h, 67%.
(E)-3-(4-Methoxyphenyl)-1-(10H-phenothiazin-8-yl)prop-
2-en-1-one (3b). Yield 93%, m.p. 208–210ꢀC, IR (KBr)
cm−1:3349 (NH), 3051 (Ar-H), 2963 (C==H), 1658 (C==O),
phenothiazine 2-yl)-pyrimidin-2(1H)-one/thione derivatives
from corresponding chalcones. All compounds of the series
showed moderate to good biological activity. Hence, it is
concluded that there is ample scope for further developing
this field.
1
1609 (C==C); H NMR (DMSO-d6): d 8.23 (s, 1H, NH), 7.95
(d, J = 3.8 Hz, 1H, ==CH-Ar), 7.55 (d, J = 3.6 Hz, 1H,
==COCH==), 7.30–6.66 (m, 11H, Ar-H); 13C NMR (DMSO-
d6): d 55.1 (OCH3); 117.8, 120.9, 121.3, 122.5, 125.3, 126.2,
129.8, 130.1, 133.6, 139.3, 140.8, 141.2, 141.8, 143.8, 144.1,
145.3 (Ar-C, ==CH==CH==C==O), 149.2 (==CH==CH==C==O),
162.3 (Ar-C==OCH3), 188.4 (C==O), Ms: m/z (%): 359 (88),
226 (72), 198 (45), 133 (50). Anal. Calcd for C22H17NO2S:
C, 73.51; H, 4.77; N, 3.90. Found: C, 73.39; H, 4.58; N, 3.73%.
(E)-3-(4-Chlorophenyl)-1-(10H-phenothiazin-8-yl)prop-2-
en-1-one (3c). Yield 96%, m.p.175–178ꢀC, IR (KBr)
cm−1:3346 (NH), 3048 (Ar-H), 1660 (C==O), 1610 (C==C),
740 (C==Cl); 1H NMR (DMSO-d6): d 8.17 (s, 1H, NH), 7.93
(d, J = 3.8 Hz, 1H, ==CH-Ar), 7.55 (d, J = 3.6 Hz,1H,
==COCH==), 7.26–6.66 (m, 12H, Ar-H); 13C NMR (DMSO-
d6): d 117.3, 120.1, 120.5, 121.1, 121.9, 124.6, 125.7, 127.9,
128.7, 129.8, 132.9, 138.5, 140.2, 141.3, 143.5, 144.0, 144.8
(Ar-C, ==CH==CH==C==O), 147.9 (==CH==CH==C==O), 189.1
(C==O); Ms: m/z (%): 363 (85), 226 (70), 198 (48), 137 (52).
EXPERIMENTAL
General procedures. All chemicals were purchased from
Aldrich and Merck chemicals, Mumbai (India) and were used
without further purification. Melting points were determined in
open capillaries using a Toshniwal melting point apparatus and
are uncorrected. Formation of compound was routinely checked
by TLC using Silica G, and the spots were exposed to iodine
vapor for visualization. The IR spectra in KBr were recorded on
a Perkin-Elmer FTIR spectrometer (nmax in cm−1); 1H NMR
and 13C NMR spectra were obtained in DMSO-d6 on a Brucker
300 MHz instrument using TMS as internal standard (chemical
shifts in d, ppm), mass spectra on LCQ Adavantage Therma
Finiger spectrometer. Elemental analysis was performed on
Carlo Erba 1108 analyzer.
General Procedure for synthesis of compounds 3a–d. To
a solution of 2-acetyl phenothiazine 1 (0.01mol) in absolute
methanol (50 mL), benzaldehyde 2a (0.01 mol) in 40%
methanolic KOH (10 mL) was added and refluxed for 2–3 h at
70ꢀC. The reaction mixture was then cooled to room temperature
and poured on to crushed ice containing few drops of conc. HCl.
The solid, thus, obtained was filtered and recrystallized from
methanol to give 3a.
Table 1
Physical data of compounds 4a–p.
Compound
R
R1
Z
m.p. (ꢀC)
Yield (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
H
OCH3
Cl
OH
H
OCH3
Cl
OH
H
OCH3
Cl
OH
H
OCH3
Cl
OH
H
H
H
O
O
O
O
O
O
O
O
S
260−262
266–268
268–270
264–266
180–182
187–189
192–194
189–192
112–114
123–125
165–167
178–181
142–146
118–121
128–130
136–138
63
68
64
71
67
65
64
72
67
69
68
76
68
66
71
60
Similarly, chalcones 3b–d were synthesized by condensing
2-acetyl phenothiazine with various aldehydes 2b–d.
H
Ph
Ph
Ph
Ph
H
(E)-1(10H-Phenothiazin-8-yl)-3-phenyl-2-en-1-one (3a). Yield
90%, m.p.201–203ꢀC, IR (KBr) cm−1:3352 (NH), 3056 (Ar-
H), 1653 (C==O), 1606 (C==C); 1H NMR (DMSO-d6): d 8.11
(s, 1H, NH), 7.88 (d, J = 3.8 Hz, 1H, ==CH-Ar), 7.56 (d, J = 3.6
Hz, 1H, ==COCH==), 7.38–6.69 (m, 12H, Ar-H); 13C NMR
(DMSO-d6): d 118.5, 119.8, 120.8, 127.1, 127.9, 129.5, 131.9,
132.8, 133.9, 135.2, 136.8, 140.3, 141.6, 143.9, 144.9,
146.1, 147.6 (Ar-C, ==CH==CH==C==O), 151.3 (==CH==CH==C;
==O), 187.2 (C==O); Ms: m/z (%): 329 (85), 226 (76), 198 (40),
103 (55). Anal. Calcd for C21H15NOS: C, 76.57; H, 4.59; N,
4.25. Found: C, 76.42; H, 4.48; N, 4.33%.
H
S
H
S
H
S
Ph
Ph
Ph
Ph
S
S
S
S
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1006
T. N. Bansode and G. A. Meshram
Vol 49
Anal. Calcd for C21H14ClNOS: C, 69.32; H, 3.88; N, 3.85.
Found: C, 69.19; H, 3.64; N, 3.73%.
Ar-H), 8.05 (s, 1H, NH, pyrimidine), 7.73 (d, J = 8.1 Hz, 2H,
Ar-H), 7.33–6.69 (m, 7H, Ar-H), 5.61 (s,1H), 5.56 (s,1H); 13C
NMR (DMSO-d6): d 116.8, 119.5, 120.3, 121.6, 122.1, 122.8,
123.5, 124.8, 128.3, 128.9, 129.4, 130.8, 131.3, 139.8, 140.4,
(Ar-C), 108.7, 158.1, 159.7, 167.6, 168.5 (pyrimidine-C,
Ar-C==OH); MS: m/z (%): 384 [M+-1] (98), 356 (66), 330 (40),
and 328 (28); Anal. Calcd for C22H15N3O2S: C, 68.55; H, 3.92;
H, 10.90. Found: C, 68.48; H, 3.82; N, 10.99%.
(E)-3-(4-Hydroxyphenyl)-1-(10H-phenothiazin-8-yl)prop-
2-en-1-one (3d). Yield 92%, m.p. 175–178ꢀC, IR (KBr)
cm−1:3353 (NH), 3054 (Ar-H), 1660 (C==O), 1611 (C==C);
1H NMR (DMSO-d6): d 8.11 (s, 1H, NH), 7.91 (d, J = 3.8 Hz,
1H, ==CH-Ar), 7.55 (d, J = 3.6 Hz, 1H, ==COCH==), 7.18–6.69
(m, 11H, Ar-H), 5.23 (s,1H); 13C NMR (DMSO-d6):
d
114.3, 116.9, 119.3, 120.4, 120.9, 121.8, 124.9, 125.4, 128.6,
129.7, 132.9, 138.4, 141.2, 142.5, 143.6, 144.1 (Ar-C,
==CH==CH==C==O), 147.3 (==CH==CH==C==O), 160.3 (Ar-C==OH),
191.1 (C==O); Ms: m/z (%): 345 (80), 226 (68),198 (50), 119
(48). Anal. Calcd for C21H15NO2S: C, 73.02; H, 4.38; N, 4.06.
Found: C, 72.86; H, 4.08; N, 3.93%.
4-(10H-Phenothiazin-2-yl)-1,6-diphenylpyrimidin-2(1H)-one
(4e). IR (KBr) cm−1: 3343 (NH), 3050 (Ar-H), 1591 (C==N),
1
1467 (C==C pyrimidine); H NMR (DMSO-d6): d 8.35 (s, 1H,
NH, phenothiazine), 7.87–6.69 (m, 17H, Ar-H), 5.39 (s, 1H);
13C NMR (DMSO-d6): d 117.8, 118.5, 119.6, 120.4, 120.8,
121.6, 122.1, 125.3, 127.4, 128.1, 129.3, 129.8, 130.6, 132.4,
134.1, 134.9, 135.3, 136.2, 142.1, 142.8 (Ar-C), 103.2, 153.1,
156.2, 162.5 (pyrimidine-C); MS: m/z (%): 444 [M+-1] (88),
416 (60), 326 (48), 312 (20), and 238 (38); Anal. Calcd for
C28H19N3OS: C, 75.48; H, 4.30; N, 9.43. Found: C, 75.57; H,
4.51; N, 9.32%.
General procedure for synthesis of compounds 4a–p.
A
mixture of chalcone 3a (0.01 mol) and urea/phenyl urea/
thiourea/phenyl thiourea (0.03 mol) in methanolic KOH (10 mL)
was refluxed for 4 h at 70ꢀC. The solid, thus, obtained was
washed with water and recrystallized from methanol to give
4a–d.
6-(4-Methoxyphenyl)-4-(10H-phenothiazin-2-yl)-1-phenylpyrimidin-
2(1H)-one (4f). IR (KBr) cm−1: 3336 (NH), 3048 (Ar-H), 1593
Similarly, 4e–p were synthesized by using chalcones 3b–d.
1
(C==N), 1469 (C==C pyrimidine); H NMR (DMSO-d6): d 8.11
4-(10H-Phenothiazin-2-yl)-6-phenylpyrimidin-2(1H)-one
(4a). IR (KBr) cm−1: 3331 (NH), 3056 (Ar-H), 1593 (C==N),
(s, 1H, NH, phenothiazine), 7.78 (d, J = 8.4 Hz, 2H, Ar-H),
7.46 (d, J = 8.2 Hz, 2H, Ar-H), 7.35–6.69 (m, 12H, Ar-H),
5.37 (s, 1H), 3.73 (s, 3H); 13C NMR (DMSO-d6): d 56.7
(OCH3), 116.3, 118.6, 119.6, 120.8, 121.5, 122.3, 123.1,
124.3, 126.1, 128.3, 129.7, 130.3, 131.8, 134.4, 134.9, 135.5,
136.3, 143.8, 144.2 (Ar-C), 104.7, 158.1, 161.6, 168.3
(pyrimidine-C, Ar-C==OCH3 ); MS: m/z (%): 474 [M+-1] (96),
446 (70), 356 (54), 342( 30), and 238 (42); Anal. Calcd for
C29H21N3OS: C, 73.14; H, 4.55; N, 8.84. Found: C, 73.27; H,
4.41; N, 8.89%.
1
1466 (C==C pyrimidine); H NMR (DMSO-d6): d 8.75 (s, 1H,
NH, phenothiazine), 8.28 (d, J = 8.4 Hz, 2H, Ar-H), 8.06 (s,
1H, NH, pyrimidine), 7.69–6.66 (m, 12H, Ar-H), 5.50 (s, 1H);
13C NMR (DMSO-d6): d 118.1, 119.8, 120.6, 120.9, 121.8,
127.1, 128.2, 128.9, 130.6, 134.6, 134.9, 135.3, 136.4, 137.1,
144.9, 145.1 (Ar-C), 109.2, 154.3, 166.4, 166.9 (pyrimidine-C);
MS: m/z (%): 368 [M+-1] (98), 340 (74), 312 (46), and 238
(32). Anal. Calcd for C22H15N3OS: C, 71.52; H, 4.09; N, 11.37.
Found: C, 71.37; H, 4.01; N, 11.29%.
6-(4-Methoxyphenyl)-4-(10H-phenothiazin-2-yl)pyrimidine-
6-(4-Methoxyphenyl)-4-(10H-phenothiazin-2-yl)pyrimidin-2
2(1H)-thione (4j). IR (KBr) cm−1: 3349 (NH), 3056 (Ar-H),
(1H)-one (4b). IR (KBr) cm−1: 3341 (NH), 3056 (Ar-H), 1577
1
1
1577 (C==N), 1468 (C==C pyrimidine), 1270 (C==S); H NMR
(C==N), 1468 (C==C pyrimidine); H NMR (DMSO-d6): d 8.79
(DMSO-d6): d 8.59 (s, 1H, NH, phenothiazine), 8.08 (d, J =
8.1 Hz, 2H, Ar-H), 8.02 (s, 1H, NH, pyrimidine), 7.86 (d, J =
8.0 Hz, 2H, Ar-H), 7.47–6.60 (m, 7H, Ar-H), 5.38 (s, 1H),
3.65 (s, 3H); 13C NMR (DMSO-d6): d 56.2 (OCH3), 115.3,
118.2, 119.4, 120.7, 121.4, 122.8, 123.6, 127.4, 128.6, 129.5,
134.5, 135.6, 136.4, 144.4, 144.7 (Ar-C), 104.9, 160.3, 165.8,
178.6, 181.2 (pyrimidine-C, Ar-C==OCH3), MS: m/z (%): 415
[M+] (100), 371 (70), 342 (40) and 238 (22); Anal. Calcd for
C23H17N3OS2: C, 66.48; H, 4.12; N, 10.11. Found: C, 66.59;
H, 3.90; N, 10.19%.
6-(4-Chlorophenyl)-4-(10H-phenothiazin-2-yl)pyrimidine-2
(1H)-thione (4k). IR (KBr) cm−1: 3347 (NH), 3050 (Ar-H),
1576 (C==N), 1465 (C==C pyrimidine), 1273 (C==S); 1H NMR
(DMSO-d6): d 8.52 (s, 1H, NH, phenothiazine), 8.18 (d, J = 8.1
Hz, 2H, Ar-H), 7.93 (s, 1H, NH, pyrimidine), 7.86 (d, J = 8.0 Hz,
2H, Ar-H), 7.26–6.63 (m, 7H, Ar-H), 5.36 (s,1H); 13C NMR
(DMSO-d6): d 118.3, 120.4, 121.3, 121.9, 122.6, 123.3, 128.3,
128.8, 129.7, 133.5, 134., 135.6, 135.5, 136.2, 143.6, 143.8
(Ar-C), 105.7, 166.3, 178.5, 181.4 (pyrimidine-C); MS: m/z (%):
419 [M+] (96), 375 (78), 346 (24), and 238 (28); Anal. Calcd for
C23H14N3S2Cl: C, 62.92; H, 3.36; N, 10.01. Found: C, 63.04; H,
3.49; N, 9.89%.
(s, 1H, NH, phenothiazine), 8.28 (d, J = 8.4 Hz, 2H, Ar-H),
8.02 (s, 1H, NH, pyrimidine), 7.71 (d, J = 8.1 Hz, 2H, Ar-H),
7.63–6.67 (m, 7H, Ar-H), 5.61 (s,1H), 3.68 (s,3H); 13C NMR
(DMSO-d6): d 55.8 (OCH3), 115.4, 118.1, 119.3, 120.6, 121.2,
122.6, 127.1, 127.8, 128.5, 129.6, 130.1, 130.3, 139.4, 140.1,
142.7 (Ar-C), 105.4, 162.3, 163.6, 165.4, 166.2 (pyrimidine-C,
Ar-C==OCH3), MS: m/z (%): 398 [M+-1] (99), 370 (78), 328
(15),300 (50), and 240 (48); Anal. Calcd for C23H17N3O2S: C,
69.15; H, 4.29; N, 10.52. Found: C, 69.01; H, 4.11; N, 10.40%.
6-(4-Chlorophenyl)-4-(10H-phenothiazin-2-yl)pyrimidin-2
(1H)-one (4c). IR (KBr) cm−1: 3339 (NH), 3056 (Ar-H), 1583
1
(C==N), 1466 (C==C pyrimidine); H NMR (DMSO-d6): d 8.77
(s, 1H, NH, phenothiazine), 8.29 (d, J = 8.4 Hz, 2H, Ar-H),
8.04 (s, 1H, NH, pyrimidine), 7.74 (d, J = 8.1 Hz, 2H, Ar-H),
7.23–6.89 (m, 7H, Ar-H), 5.68 (s, 1H); 13C NMR (DMSO-d6):
d 118.2, 120.2, 120.8, 121.3, 122.5, 123.1, 128.5, 128.8, 129.6,
133.8, 134.3, 135.3, 135.8, 136.1, 141.6, 141.9 (Ar-C), 107.7,
157.1, 166.8, 167.5 (pyrimidine-C); MS: m/z (%): 402 [M+-1]
(100), 374 (60), 344 (38), 314 (52) and 238 (28); Anal. Calcd
for C22H14N3SOCl: C, 65.45; H, 3.49; N, 10.40. Found: C,
65.59; H, 3.31; N, 10.22%.
6-(4-Hydroxyphenyl)-4-(10H-phenothiazin-2-yl) pyrimidin-2
6-(4-Chlorophenyl)-4-(10H-phenothiazin-2-yl)-1-phenylpyr-
(1H)-one (4d). IR (KBr) cm−1: 3340 (NH), 3048 (Ar-H),
imidine-2(1H)-thione (4o). IR (KBr) cm−1: 3366 (NH), 3048
1
1
(Ar-H), 1591 (C==N), 1463 (C==C pyrimidine), 1272(C==S); H
1575 (C==N), 1466 (C==C pyrimidine); H NMR (DMSO-d6): d
NMR (DMSO-d6): d 8.19 (s, 1H, NH, phenothiazine), 8.08 (d,
8.71 (s, 1H, NH, phenothiazine), 8.26 (d, J = 8.3 Hz, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2012
Synthesis and Antimicrobial Activity of 6-(10H-Phenothiazin-2-yl)
Pyrimidin-2(1H)-one/thione Derivatives
1007
Table 2
Antibacterial activity of the compounds 4a–p.
Antibacterial activity
Compound
Bacillus subtilis
Escherichia coli
Staphylococcus aureus
Pseudomonas aeruginosa
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
10(25)
14(5)
18(10)
16(5)
18(5)
19(10)
20(15)
22(15)
21(10)
20(15)
19(5)
12(5)
12(25)
12(5)
17(15)
18(10)
16(20)
20(20)
21(15)
15(5)
12(25)
12(25)
22(5)
20(25)
21(20)
15(20)
17(25)
19(25)
10(10)
8(10)
10(25)
11(15)
14(10)
17(15)
14(15)
10(20)
23(5)
12(25)
18(25)
16(20)
17(15)
15(20)
20(15)
13(5)
16(25)
17(25)
18(15)
17(15)
14(20)
11(20)
12(15)
24(5)
20(5)
24(5)
15(5)
12(25)
14(20)
19(20)
20(15)
21(10)
22(20)
24(5)
24(10)
26(15)
25(20)
24(20)
21(20)
26(5)
Ampicillin
MIC values are given in brackets; MIC (μg/mL) = minimum inhibitory concentration, that is, lowest concentration to completely inhibit bacterial growth;
zone of inhibition is expressed in mm.
J = 8.2 Hz, 2H, Ar-H), 7.66 (d, J = 8.0 Hz, 2H, Ar-H), 7.25–6.66
(m, 12H, Ar-H), 5.37 (s, 1H); 13C NMR (DMSO-d6): d 117.9,
119.6, 120.5, 120.9, 121.7, 122.3, 125.6, 127.6, 128.3, 129.2,
130.2, 130.7, 133.5, 134.2, 134.4, 135.3, 136.2, 137.4, 142.1,
142.8 (Ar-C), 104.6, 157.3, 168.5, 181.2 (pyrimidine-C); MS:
m/z (%): 495 [M+] (99), 451 (66), 360 (36), 347 (52), and 238
(22); Anal. Calcd for C28H18N3S2Cl: C, 67.80; H, 3.66; N, 8.47.
Found: C, 67.97; H, 3.51; N, 8.29%.
6-(4-Hydroxyphenyl)-4-(10H-phenothiazin-2-yl)-1-phenylpyr-
imidine-2(1H)-thione (4p). IR (KBr) cm−1: 3360 (NH), 3052
1
(Ar-H), 1578 (C==N), 1465 (C==C pyrimidine); 1272 (C==S); H
NMR (DMSO-d6): d 8.13 (s, 1H, NH, phenothiazine), 8.04 (d,
J = 8.2 Hz, 2H, Ar-H), 7.69 (d, J = 8.0 Hz, 2H, Ar-H), 7.28–
6.67 (m, 12H, Ar-H), 5.57 (s, 1H), 5.37 (s, 1H); 13C NMR
(DMSO-d6): d 116.6, 118.6, 120.8, 121.5, 122.3, 123.1, 124.4,
127.9, 128.8, 129.7, 131.3, 132.2, 133.7, 134.5, 135.8, 136.3,
Table 3
Antifungal activity of the compounds 4a−p.
Antifungal activity
Compound
Aspergillus niger
Aspergillus fumigatus
Aspergillus flavus.
Candida albicans
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
17(5)
18(5)
12(5)
18(5)
18(5)
18(5)
22(10)
22(10)
19(10)
16(10)
20(25)
18(5)
14(15)
16(15)
20(15)
13(10)
17(15)
13(15)
19(10)
17(15)
21(5)
10(15)
13(15)
10(15)
13(15)
12(10)
20(20)
21(20)
20(25)
12(20)
12(20)
12(20)
14(15)
12(15)
14(20)
13(20)
14(20)
19(5)
17(10)
16(15)
15(10)
18(20)
17(20)
14(15)
12(15)
12(15)
23(10)
25(20)
24(20)
25(20)
22(20)
24(5)
18(5)
10(5)
18(5)
10(5)
18(10)
19(15)
21(20)
20(20)
19(15)
22(5)
20(10)
25(15)
26(15)
22(15)
24(20)
16(5)
4o
4p
Fluconazole
MIC values are given in brackets, MIC (μg/mL) = minimum inhibitory concentration, that is, lowest concentration to completely inhibit fungal growth;
zone of inhibition is expressed in mm.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1008
T. N. Bansode and G. A. Meshram
Vol 49
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137.6, 143.8, 144.2 (Ar-C), 104.1, 158.2, 165.6, 181.3
(pyrimidine-C, Ar-C==OH ); MS: m/z (%): 477 [M+] (96), 433
(74), 342 (28), 329 (40), and 238 (28); Anal. Calcd for
C28H19N3S2O: C, 70.41; H, 4.01; N, 8.80. Found: C, 70.59; H,
4.06; N, 8.90%.
BIOLOGICAL ACTIVITY
Antibacterial activity. The newly synthesized compounds
were screened for their antibacterial activity against Bacillus
subtillis (ATCC-11774), Escherichia coli (ATCC-25922),
Staphylococcus aureus (ATCC-25923), and Pseudomonas
aeruginosa (ATCC-27853) bacterial strains by disc diffusion
method [27, 28]. The test compounds were prepared with
different concentrations using dimethylsuphoxide. The discs
of each concentration were placed in triplicate in nutrient
agar medium seeded with fresh bacteria separately. The
incubation was carried out at 37ꢀC for 24 h. Ampicillin was
used as a standard drug. Solvent and growth controls were
prepared and kept. Zones of inhibition and minimum
inhibitory concentrations (MICs) were noted. The results of
antibacterial studies are given in Table 2.
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Antifungal activity. Newly prepared compounds were
screened for their antifungal activity against Aspergillus
niger (NCIM no. 617), Aspergillus flavus (NCIM no.
524), Aspergillus fumigatus (NCIM no. 902), and
Candida albicans (NCIM no. 300) in DMSO by serial
plate dilution method [29, 30]. Sabouraud agar media
were prepared by dissolving peptone (1 g), D-glucose (4
g) and agar (2 g) in distilled water (100 mL) and adjusting
pH to 5.7. A particular fungal strain was transferred to
3-mL saline to get a suspension of corresponding species.
Agar media (20 mL) were poured into each Petri dish.
The plates were dried by placing in an incubator at 37ꢀC
for 1 h. Using an agar punch, wells were made and each
well was labeled. A control was also prepared in triplicate
and maintained at 37ꢀC for 2 to 3 days. Zone of inhibition
and MIC were noted. The activity of each compound was
compared with fluconazole as the standard drug. The
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REFERENCES AND NOTES
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet