Synthesis and antibacterial activity of novel 4-{4-(methylamino)thieno[3,2-d]pyrimidin-2-yl}-benzohydrazide derivatives

Article abstract of DOI:10.1134/S1070363217060238

A series of novel 4-{4-(methylamino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide derivatives were synthesized and evaluated for their antibacterial activity. Most of the compounds demonstrated high activity towards Escherichia coli, Pseudomonas, Staphylococcus aureus, and Bacillus. Structures of all synthesized compounds were confirmed by spectral analysis.

Full text of DOI:10.1134/S1070363217060238

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 6, pp. 1275–1280. © Pleiades Publishing, Ltd., 2017.
Synthesis and Antibacterial Activity of Novel
4
-{4-(Methylamino)thieno[3,2-d]pyrimidin-2-yl}-benzohydrazide
1
Derivatives
a
a
a
b
c
T. Giri , G. Sailaja , E. Laxminarayana *, M. Thirumala Chary , and M. Ramesh
a
Sreenidhi Institute of Science and Technology (Autonomous), Ghatkesar, Hyderabad, Telangana, 501301 India
e-mail: elxnkits@yahoo.co.in
*
b
Jawaharlal Nehru Technological University Hyderabad, Hyderabad, Telangana, 500085 India
c
Jawaharlal Nehru Technological University Kakinada, Kakinada, Telangana, 533003 India
Received February 28, 2017
Abstract—A series of novel 4-{4-(methylamino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide derivatives
were synthesized and evaluated for their antibacterial activity. Most of the compounds demonstrated high
activity towards Escherichia coli, Pseudomonas, Staphylococcus aureus, and Bacillus. Structures of all
synthesized compounds were confirmed by spectral analysis.
Keywords: hydrazones, antibacterial activity, thieno pyrimidine, microwave irradiation
DOI: 10.1134/S1070363217060238
Hydrazones derivatives are used widely in
NMP (1.0 mL, catalytic) and POCl (35 mL) at room
3
synthesis of heterocycles [1] and demonstrate a broad
spectrum of biological and medicinal properties
including antimicrobial, antimycobacterial, anticon-
vulsant, anti-inflammatory, and other types of activity
temperature. Following refluxing of the mixture tasted
for 16 h. Upon completion of the reaction, excess of
POCl was distilled off. The residue was poured into
3
ice cold water and filtered off to give the compound 3
1
[2–11]. Hydrazone derivatives contain the highly
as off white solid, yield 80%, mp 136–140°C. H
reactive azomethine group (CO–NH–N=CH) making
those important in new drugs development [4].
NMR spectrum, δ, ppm: 7.72 d (J = 5.5 Hz, 1H, ArH),
8.70 t (J = 4.4 Hz, 1H, ArH). ESI–MS: m/z: 204.9
+
[
M + H] .
EXPERIMENTAL
N-(2-Chlorothieno[3,2-d]pyrimidin-4-yl)-N-methyl-
amine (5). To a solution of 2,4-dichlorothieno[3,2-d]-
pyrimidine (3) (7 g, 34.31 mmol) in THF (80 mL)
were added 9 mL of aqueous solution (40%) of methyl
amine and stirred at room temperature for 3 h. Upon
completion of the process, the reaction mixture was
concentrated and poured into ice water. The compound
All chemicals were purchased from Aldrich. All
solvents were of analytical grade. Melting points were
determined in open glass capillaries on a Stuart
SMP30 apparatus. TLC was carried out on Merck AL
silica gel 60 F254 plates and visualized under UV light.
IR spectra were recorded in KBr pellets on a Shimadzu
1
13
5 was formed as off white solid, yield 88%, mp 294–
FTIR spectrophotometer. H and C NMR spectra
1
3
3
8
03°C. H NMR spectrum, δ, ppm: 2.96 d (J = 4.5 Hz,
H), 7.32 s (1H, NH), 8.16 d (J = 4.7 Hz, 1H, ArH),
were measured in DMSO-d on a Varian Mercury plus
6
4
00 MHz spectrometer using TMS as the internal
.34 d (J = 4.7 Hz, 1H, ArH). ESI–MS: m/z: 200.1
standard. Mass spectra were measured on a Shimadzu
LCMS-QP 1000 mass spectrometer. All reactions were
carried out under inert atmosphere.
+
[
M + H] .
tert-Butyl-N-(2-chlorothieno[3,2-d]pyrimidin-4-
yl)-N-methylcarbamate (6). To a solution of N-(2-
chlorothieno[3,2-d]pyrimidin-4-yl)-N-methylamine (5)
2
,4-Dichlorothieno[3,2-d]pyrimidine (3) (see
Scheme 1). To a suspension of theno[3,2-d]pyrimidine-
,4-diol (2) (8.0 g, 47.61 mmol) in toluene were added
(
(
6.0 g, 30.15 mmol) in DMF (42 mL) were added TEA
2
6 g, 60.30 mmol) and (Boc) O (7.9 g, 36.18 mmol ) at
2
1
The text was submitted by the authors in English.
room temperature. The mixture was stirred for 4 h. The
1
275

1
276
GIRI et al.
Scheme 1. Synthesis of thienopyrimidine amide derivatives 11a–11k.
NH
N
OH
Cl
CO Me
2
S
S
S
a
N
N
N
S
b
c
NH2
Me
NH2
N
OH
N
Cl
Cl
1
2
3
4
5
NH
Boc
N
NH
N
g
S
f
S
N
S
N
N
N
N
d
OH
O
CN
O
O
1
0
9
8
OH
B
h
HO
e
Boc
N
CN
N
N
7
NH
S
NH
Aldehydes
S
N
a−k
Cl
S
N
i
6
N
H
N
N
H
N
N
Ar
NH2
O
1
1
11a−11k
O
O
H
H CO
OCH3
O
3
H
N
N
(
a), O
(c),
N
(d),
(e),
Ar =
(b), O
Cl
O
OCH3
O
O
O
O
O
O
O
F
NO2
(
f),
(g),
(h),
(i),
(j),
(k).
O
OEt
N
O
N
O
O
N
H
Reagents and conditions: (a): KOCN, AcOH, H
4 h; (c) THF, room temperature, 3 h; (d) (Boc)
DME, water, 120°C, 1 h; (f) EtOH, 6 N NaOH, 80°C, 16 h; (g) H
h; (i) P-TSA, 120°C 1 h.
2
O, room temperature, 18 h; NaOH, room temperature, 4 h; (b) POCl
O, DMF, TEA, room temperature, 4 h; (e) Pd(amphos)Cl , Na
·NH ·H
3
, reflux,
2
2
2
2
3
CO , 20%
2
SO
4
(conc.), EtOH, reflux, 4 h; (h) NH
2
2
2
O, 100°C ,
1
1
reaction mixture was poured into ice cold water. The
precipitate was dried under vacuum to give pure
compound 6 as off white solid, yield 82%, mp 126–
1378, 1247, 1144, 886, 793. H NMR spectrum, δ,
ppm: 1.50 s [9H, C(CH ) ], 3.39 s (3H, CH ), 7.54 d
(J = 5.5 Hz, 1H, ArH), 8.51 d (J = 5.5 Hz, 1H, ArH).
3
3
3
–1
+
1
30°C. IR spectrum, ν, cm : 3068, 2978, 1716, 1532,
ESI–MS: m/z: 299.9 [M + H] .
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
1277
tert-Butyl-2-(4-cyanophenyl)thieno[3,2-d]pyrimidin-
-ylmethylcarbamate (8). To a solution of tert-butyl-
the compound 10 as off white solid, yield 85%, mp 154–
160°C. IR spectrum, ν, cm : 3401, 3369, 2975, 2930,
–
1
4
N-(2-chlorothieno[3,2-d]pyrimidin-4-yl)-N-methyl-
carbamate (6) (4.7 g, 15.71 mmol) in DME (70 mL)
and water (24 mL) was added 4-cyano phenyl boronic
acid (7) (2.77 g, 18.86 mmol). The mixture was purged
with Ar for 5 min and Na CO (2.54 g, 23.65 mmol)
1945, 1707, 1590, 1543, 1508, 1380, 1278, 1100,
1018. H NMR spectrum, δ, ppm: 1.41–1.45 t (J =
1
7.2 Hz, 3H), 3.33–3.35 d (J = 4.8 Hz, 3H), 4.39–4.44 q
(J = 6.8 Hz, 2H), 5.03 br.s ( H), 7.49–7.51 d (J = 5.2
Hz, 1H), 7.71–7.73 d (J = 5.5 Hz, 1H), 8.13–8.15 d
(J = 8.4 Hz, 2H), 8.57–8.60 d (J = 8.4 Hz, 2H). ESI–
2
3
and Pd(Amphos)Cl (556 mg, 0.785 mmol) were added
2
+
to it. Following Ar purging and microwave irradiation
at 120°C lasted for 1h. The reaction mixture was
poured into ice cold water, the precipitate filtered off
and washed with acetonitrile to give compound 8 as
white solid, yield 89%, mp 358–362°C. IR spectrum,
MS: m/z: 491.39 [M + H] .
4
-{(4-(Methylamino)thieno[3,2-d]pyrimidin-2-yl}-
benzohydrazide (11). The mixture of ethyl 4-{4-
methylamino)thieno[3,2-d]pyrimidin-2-yl}benzoate
(
–
1
(10) (3 g, 9.58 mmol) and hydrazine hydrate (20 mL)
was microwaved at 100°C for 1h. The reaction mixture
was poured into ice water, the precipitate filtered off
and dried under vacuum to afford products 11 as white
ν, cm : 3411, 3103, 3064, 2978, 2935, 2362, 2221,
1
1
926, 1804, 1712, 1605, 1573, 1528, 1468, 1375,
319, 1148, 1113. H NMR spectrum, δ, ppm: 1.57 s
1
(
9H), 3.58 s (3H), 7.54–7.53 d (J = 5.6 Hz, 1H), 7.79–
–
1
solid, yield 91%, mp 222–226°C. IR spectrum, ν, cm :
302, 3065, 2932, 1601, 1539, 1505, 1436, 1336,
7
8
.77 d (J = 6.8 Hz, 2H), 7.98–7.96 d (J = 5.6 Hz, 1H),
3
.64–8.62 d (J = 6.8 Hz, 2H). ESI–MS: m/z: 367.2
1
+
1109. H NMR spectrum, δ, ppm: 3.12 s (3H), 4.55
br.s ( 2H), 7.47–7.48 d (J = 5 Hz, 1H), 7.81 d (J =
[
M + H] .
4
-{4-(Methylamino)thieno[3,2-d]pyrimidin-2-yl}-
8
Hz, 1H), 7.93–7.95 d (J = 7.5 Hz, 2H), 8.13–8.14 d
benzoic acid (9). To a solution of tert-butyl-2-(4-
cyanophenyl)thieno[3,2-d]pyrimidin-4-ylmethylcar-
bamate (8) (4 g, 0.02 mmol ) in EtOH (40 mL) was
added 6N NaOH (40mL) and the mixture was stirred at
(
(
1
J = 5 Hz, 1H), 8.50–8.51 d (J = 7.5 Hz, 2H), 9.87 s
1
3
1H). C NMR spectrum, δ, ppm: 113.7, 124.6, 126.9,
27.5, 133.0, 134.2, 140.9, 157.3, 159.0, 159.9, 165.6.
+
ESI–MS: m/z: 491.39 [M + H] .
8
0°C for 16 h. The solvent was evaporated under
reduced pressure, the crude residue was acidified with
N HCl (to pH = 3), filtered off and washed with
General procedure for 4-{4-(methylamino)thieno-
[
3,2-d]pyrimidin-2-yl}-N'-arylmethylene benzohyd-
razide derivatives (11a–11k). To a solution of 4-{4-
methylamino)thieno[3,2-d]pyrimidin-2-yl}benzo-
hydrazide (11a–11k) (100 mg, 0.33 mmol) in ethanol
4 mL) were added an aldehyde (0.33 mmol) and
PTSA (catalytic amount). The mixture was heated at
20°C for 1 h. The reaction mixture was poured into
2
water. The product was dried under vacuum to give the
(
compound 9 as off white solid, yield 93%, mp 330–
–
1
3
1
34°C. IR spectrum, ν, cm : 3338, 3287, 3041, 1696,
1
(
634, 1589, 1554, 1426, 1381, 1295, 1168, 1045. H
NMR spectrum, δ, ppm: 3.19–3.20 d (J = 4 Hz, 3H),
1
7
2
8
.62–7.63 d (J = 5.2 Hz, 1H), 8.12–8.14 d (J = 8.4 Hz,
H), 8.33–8.38 d (J = 5.2 Hz, 1H), 8.52–8.54 d (J =
ice cold water (4 mL). The precipitate was filtered off and
washed with ethyl acetate to afford a compounds 11a–11k.
.4 Hz, 2H), 9.18 br.s (1H). ESI–MS: m/z: 491.39
+
[
M + H] .
N'-(4-Chlorobenzylidene)-4-{4-(methylamino)-
thieno[3,2-d]pyrimidin-2-yl}benzohydrazide (11a).
White solid, yield 87%, mp 282–290°C. IR spectrum,
ν, cm : 3332, 3242, 3052, 2928, 2856, 1649, 1582,
1535, 1492, 1388, 1347, 1275, 1047 H NMR spec-
trum, δ, ppm: 3.14–3.13 s (J = 4.4 Hz, 3H), 7.48–7.56
m (3H), 7.78–7.80 d (J = 8 Hz, 2H), 7.95–7.96 d (J =
4.4 Hz, 1H), 8.03–8.05 d (J = 8 Hz, 2H), 8.13–8.14 d
(J = 5.2 Hz, 1H), 8.49–8.59 m (3H), 12.01 s (1H). C
NMR spectrum, δ, ppm: 18.5, 27.2, 56.0 113.8, 124.6,
127.5–127.7, 128.4–128.9, 133.1–133.4, 134.3–134.6,
141.4, 146.4, 157.3, 158.9, 159.9, 163.2. MS (ESI):
Ethyl 4-{4-(methylamino)thieno[3,2-d]pyrimidin-
-yl}benzoate (10). To a solution of 4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzoic acid (9)
4g, 14 mmol) in EtOH (160 mL) was added drop wise
H SO (conc., 4 mL). The reaction mixture was
2
–
1
1
(
.
2
4
refluxed for 4 h and poured into ice water and the
solvent was evaporated. The residue was treated by ice
water basified with Na CO and extracted with DCM
13
2
3
(
20×3 mL). The combined extracts were washed with
water and brine solution and dried over Na SO . The
2
4
crude residue was filtered off and dried to give the
crude product which was purified by column
chromatography (eluent 2% MeOH in DCM) to afford
+
m/z 422.2 [M + H] . HRMS (ESI): m/z: Found
422.0825. C21
+
H
17
N
OSCl. Calculated 422.0842. [M + H] .
5
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

1
278
GIRI et al.
N'-[(Benzofuran-5-yl)methylene]-4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
11b). Off-white solid, yield 93%, mp 305–309°C. IR
N'-(2-Ethoxybenzylidene)-4-{4-(methylamino)-
thieno[3,2-d]pyrimidin-2-yl}benzohydrazide (11f).
Off-white solid, yield 89%, mp 216–220°C. H NMR
1
(
–
1
spectrum, ν, cm : 3445, 3249, 3055, 2926, 1647,
spectrum, δ, ppm: 1.39–1.43 t (J = 6.8 Hz, 3H), 3.13–
3.14 d (J = 4.4 Hz, 3H), 4.12–4.17 q (J = 7 Hz, 2H),
7.01–7.05 t (J = 7.6 Hz, 1H), 7.09–7.11 d (J = 8.4 Hz,
1H), 7.39–7.43 t (J = 7.6 Hz, 1H), 7.48–7.50 d (J =
7.6 Hz, 1H), 7.92–8.05 m (2H), 8.07–8.10 d (J =
12 Hz, 2H), 8.13–8.15 d (J = 5.2 Hz, 1H), 8.54 s (1H),
1
1
581, 1538, 1430, 1350, 1275, 1036. H NMR spec-
trum, δ, ppm: 3.14 d (J = 4.8 Hz, 3H), 7.080 br.s (1H),
.48–7.50 d (J = 5.6 Hz, 1H), 7.69–7.79 m (2H), 7.96
7
br.s (1H), 8.03–8.18 m (5H), 8.56–8.59 m (3H). ESI–
+
MS: m/z: 428.43 [M + H] . HRMS (ESI): m/z: Found
+
13
4
28.1186. C H N O S. Calculated 428.1181. [M + H] .
8.56–8.58 d (J = 8 Hz, 2H), 11.97 (s,1H). C NMR
23
18
5
2
spectrum, δ, ppm: 14.6, 27.2, 61.7, 63.7, 79.1, 112.7,
N'-[(1H-Indol-6-yl)methylene]-4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
11c). Off-white solid, yield 82%, mp 296–300°C. IR
1
1
13.8, 120.6, 122.5, 124.6, 125.5, 126.8, 127.5–127.7,
28.4, 131.4, 133.1, 134.4, 141.4, 143.3, 156.6, 157.1–
(
–
1
157.3, 158.9, 159.9, 162.7. ESI-MS: m/z: 432.35 [M +
spectrum, ν, cm : 3300, 3257, 3078, 3050, 2925,
+
1
H] . HRMS (ESI): m/z: Found 432.1513. C23
H N O S.
22 5 2
1
644, 1586, 1543, 1351, 1285, 1047. H NMR spec-
trum, δ, ppm: 3.13–3.14 s (J = 5 Hz, 3H), 6.49 s (1H),
.44–7.51 m (3H), 7.61–7.66 d (J = 8 Hz, 1H), 7.77 s
+
Calculated 432.1494. [M + H] .
7
N'-[4-(Dimethylamino)-2-methoxybenzylidene]-
4-{4-(methylamino)thieno[3,2-d]pyrimidin-2-yl}benzo-
hydrazide (11g). Yellow solid, yield 95%, mp 184–
(
1H), 7.96 s (1H), 8.05–8.06 d (J = 8 Hz, 2H), 8.14 s
(
1H), 8.56–8.58 m (3H), 11.33 s (1H), 11.80 br.s (1H).
C NMR spectrum, δ, ppm: 27.2, 56.0, 101.5, 110.9,
1
3
–1
188°C. IR spectrum, ν, cm : 3343, 3310, 2922, 2848,
1
1
1
13.8, 118.1, 120.3, 124.6, 127.3–127.6, 129.4, 133.1,
1654, 1596, 1541, 1358, 1294, 1246, 1113, 1026. H
34.6, 135.8, 141.4, 149.6, 157.4, 158.9, 159.9, 162.6.
NMR spectrum, δ, ppm: 3.0 s ( 6H), 3.13 s ( 3H), 3.86
s ( 3H), 6.40–6.42 d (J = 9 Hz, 1H), 7.48–7.49 d (J =
5 Hz, 1H), 7.72–7.73 d (J = 9 Hz, 1H), 7.91 br.s (1H),
7.94–7.95 d (J = 5 Hz, 1H), 8.02 m (1H), 8.03–8.06 d
+
MS (ESI): m/z: 427.27 [M + H] . HRMS (ESI): m/z:
Found 427.133. C H N OS. Calculated 427.1341.
23
19
6
+
[
M + H] .
N'-[(1H-Pyrazol-3-yl)methylene]-4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
11d). Brown solid, yield 86%, mp 274–278°C. IR
(
(
J = 8.5 Hz, 2H), 8.53–8.55 d (J = 8.5 Hz, 1H), 8.70 s
1H), 11.63 (s,1H). ESI–MS: m/z: 461.40 [M + H] .
+
HRMS (ESI): m/z: Found 467.1748. C H N O S.
2
4
25
6
2
(
+
–1
Calculated 461.1760. [M + H] .
spectrum, ν, cm : 3452, 3414, 3103, 3020, 2927, 2860,
1
1
682, 1542, 1430, 1367, 1343, 1277, 1178, 1044. H
N'-(3-Fluoro-4-methoxybenzylidene)-4{(4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
(11h). Off white solid, yield 85%, mp 253–257°C. IR
NMR spectrum, δ, ppm: 3.13–3.14 d (J = 3.6 Hz, 3H),
7
8
8
.49–7.50 d (J = 4 Hz, 1H), 6.75 s (1H), 7.67 s (1H),
.04–8.52 m (4H), 8.14–8.15 d (J = 4 Hz, 1H), 8.62–
–1
spectrum, ν, cm : 3442, 3318, 3237, 3063, 3038, 2937,
.63 d (J = 7.5 Hz, 2H), 13.56 s (1H), 13.83 s (1H).
2847, 1646, 1611, 1581, 1541, 1514, 1433, 1277,
+
1
MS (ESI): m/z: 378.43 [M + H] . HRMS (ESI): m/z:
1113, 1020. H NMR spectrum, δ, ppm: 3.13–3.14 d
Found 378.1101. C H N OS. Calculated 378.1137.
(J = 4.4 Hz, 3H), 3.90 s (3H), 7.48–7.49 t (J = 5.2 Hz,
1H), 7.51–7.53 d (J = 8.4 Hz, 2H), 7.67–7.68 d (J =
1
8
16
7
+
[
M + H] .
N'-(2,4,6-Trimethoxybenzylidene)-4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
11e). Yellow solid, yield 91%, mp 170–174°C. IR
3
.2 Hz, 1H), 7.95–7.96 d (J=4.4 Hz, 1H), 8.03–8.05 d
(
J = 8.4 Hz, 2H), 8.13–8.15 d (J = 5.2 Hz, 1H), 8.42 s
1H), 8.55–8.57 d (J = 8.4 Hz, 2H), 11.92 br.s (1H).
C NMR spectrum, δ, ppm: 27.2, 56.1–56.2, 113.3–
(
(
1
3
–1
spectrum, ν, cm : 3455, 1611, 1543, 1332, 1121, 1016.
1
113.8, 124.5–124.6, 127.6–127.6, 133.1, 134.5, 141.5,
46.6, 148.6–148.7, 150.6, 152.6, 157.4, 158.9, 159.9,
H NMR spectrum, δ, ppm: 3.18 s (3H), 3.90 s (9H),
1
6
8
.20–6.40 s (1H), 7.48–7.49 d (J = 5.6 Hz, 1H), 7.91–
+
1
3
162.9. MS (ESI): m/z: 436.31 [M + H] . HRMS (ESI):
m/z: Found 436.1263. C H N O FS. Calculated
4
.22 (4, 4H), 8.52–8.71 m (3H), 11.60 br.s (1H).
C
2
2
19
5
2
NMR spectrum, δ, ppm: 27.2, 55.4, 55.9, 91.1, 104.1,
+
36.1244. [M + H] .
1
1
13.7, 124.7, 127.5, 133.1, 134.7, 141.2, 144.0, 157.4,
59, 159.9, 162.2, 162.3. ESI–MS: m/z: 478.28 [M +
N'-[(1,2-Dihydro-2-oxopyridin-3-yl)methylene]-
4-{4-(methylamino)thieno[3,2-d]pyrimidin-2-yl}-
benzohydrazide (11i). Pale yellow sold, yield 82%,
+
H] . HRMS (ESI): m/z: Found 478.1567. C H N O S.
Calculated 478.1549. [M + H] .
24
24
5
4
+
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
Antibacterial activity of synthesized products
1279
Zone of inhibition,
mm
Zone of inhibition,
mm
Sample
Microorganism
Sample
Microorganism
1
1f
Escherichia coli
Pseudomonas
–
–
12
12
24
16
13 11i
17
Escherichia coli
12
–
13
–
15
14
19
14
Pseudomonas
Staphylococcus aureus
Bacillus
17
15
25
Staphylococcus aureus
Pseudomonas
16
–
17
13
17 11j
1
1
1g
1h
Staphylococcus aureus
Escherichia coli
13
13
16
14
17 11k
Escherichia coli
Pseudomonas
12
12
13
14
14
15
15
Pseudomonas
–
13
15
14
Staphylococcus aureus
Escherichia coli
12
30
13
32
14
35
Staphylococcus aureus
12
16 Standard –
Streptomycin
Bacillus
–
11
15
Pseudomonas
Staphylococcus aureus
Bacillus
30
31
31
31
32
35
32
34
37
–
1
mp 257–260°C. IR spectrum, ν, cm : 3542, 3321,
spectrum, δ, ppm: 3.13–3.14 d (J = 4.4 Hz, 3H), 7.486–
7.493 d (J = 2.8 Hz, 1H), 7.92–8.15 m (5H), 8.15–8.17
d (J = 8.8 Hz, 1H), 8.36–8.39 d (J = 8.4 Hz, 2H), 8.56–
8.58 d (J = 8.4 Hz, 2H), 12.27 br.s (1H). MS (ESI): m/z:
2
1
928, 2855, 1714, 1673, 1572, 1504, 1333, 1266, 1147,
094, 1050, 1003. H NMR spectrum, δ, ppm: 3.20 s
3H), 7.47–7.49 m (1H), 7.81–8.14 m (7H), 8.55–8.56
d (J = 4.8 Hz, 2H), 11.94 br.s (1H). MS (ESI): m/z:
05.28 [M + H] . HRMS (ESI): m/z: Found 405.1116.
C H N O S. Calculated 405.1134. [M + H] .
1
(
+
433.25 [M + H] . HRMS (ESI): m/z: Found 433.1025.
+
+
4
C H N O S. Calculated 433.1005. [M + H] .
2
1
16
6
3
+
2
0
17
6
2
Biological activity. Antimicrobial activity of the
N'-[(2-Methoxypyridin-3-yl)methylene]-4-{4-(methyl-
amino)thieno[3,2-d]pyrimidin-2-yl}benzohydrazide
11j). Pale yellow solid, yield 94%, mp 250–254°C. IR
samples was tested using cup-plate or cylinder plate
method. Antibacterial activity was tested by using the
microbial strains. The samples that exhibited positive
test results are listed in the table.
(
–1
spectrum, ν, cm : 3435, 3219, 3054, 2944, 2850, 1654,
1
1
587, 1537, 1460, 1398, 1348, 1279, 1013. H NMR
CONCLUSIONS
spectrum, δ, ppm: 3.13 s (3H), 3.98 s (3H), 7.11–7.14 t
(
(
5
8
4
J = 5.2, 1H), 7.49–7.50 d (J = 5.2 Hz, 1H), 7.98 br.s
1H), 8.07–8.09 d (J = 7.2 Hz, 2H), 8.14–8.15 d (J =
.6 Hz, 1H), 8.22–8.35 m (2H), 8.56–8.58 d (J =
Antibacterial activity of the samples was assessed
using different concentrations of the samples. The
zones of inhibition increased as the concentration of
the samples increased 11f–11k. The compounds 11f,
.4 Hz, 2H), 8.75 s (1H), 12.08 s (1H). MS (ESI): m/z:
+
19.28 [M + H] . HRMS (ESI): m/z: Found 419.1308.
1
1h, and 11k demonstrated antibacterial activity
+
C H N O S. Calculated 419.1290. [M + H] .
2
1
19
6
2
against Escherichia coli, Pseudomonas, Staphylo-
coccus, and Bacillus. The compound 11g demonstrated
activity against Staphylococcus aureus. The compound
11i was active against Escherichia coli, Pseudomonas,
and Staphylococcus. The compound 11j was active
against Pseudomonas.
N'-(4-Nitrobenzylidene)-4-{4-(methylamino)-
thieno[3,2-d]pyrimidin-2-yl}benzohydrazide (11k).
Pale yellow solid, yield 88%, mp 288–292°C. IR spec-
trum, ν, cm : 3316, 3244, 3062, 2922, 2851, 1658,
1
–
1
1
584, 1538, 1518, 1345, 1276, 1143, 1042. H NMR
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

1
280
GIRI et al.
6. Rollas, S., Gulerman, N., and Edeniz, H., Farmaco IL.,
REFERENCES
Int. J. Org. Chem., 2002, vol. 57, p. 171.
1
. Chimenti, F., Maccioni, E., Secci, D., Bolasco, A.,
Chimenti, P., Granese, A., Befani, O., Turini, P.,
Alcaro, S., Ortuso, F., Cardia, M.C., and Distinto, S.,
J. Med. Chem., 2007, vol. 50, p. 707. doi 10.1021/
jm060869d
7. Cukurovali, A., Yilmaz, B., Gur, S., and Kazaz, C., Eur.
J. Med. Chem., 2006, vol. 41, p. 201. doi org/10.1016/
j.ejmech.2005.01.013
8
. Mamolo, M.G., Falagiani, V., Zampieri, D., Vio, U.,
Banfi, E., and Scialino, G., Farmaco IL, J. Med. Chem.
Drug Discover., 2003, vol. 58, p. 631.
2
. Rollas, S. and Kucukguzel, S.G., Molecules, 2007,
vol. 12, p. 1910. doi 10.3390/12081910
9. Capilla, J., Serena, C., Javier, F., Ortoneda, T., and
Guarro, J., Antimicrob. Agents Chemother., 2003,
vol. 47, p. 3976.
3
. Barbazan, P., Carballo, R., Covelo, B., Lodeiro C.,
Lima, J.C., and Vazquez-Lopez, E.M., Eur. J. Inorg.
Chem., 2008, no. 17, p. 2713. doi 10.1002/
ejic.200701199
1
0. Todeschini, A.R., Miranda, A.L., Silva, C.M., Parrini, S.C.,
and Barreiro, E.J., Eur. J. Med. Chem., 1998, vol. 33, p.
1
89. doi org/10.1016/S0223-5234(98)80008-1
4
5
. Durgun, B., Capan, G., Ergenc, N., and Rollas, S.,
Pharmazie, 1993, vol. 48, no. 12, p. 942
1
1. Lima, P.C., Lima, L.M., Silva, K.C., Leda, P.H.,
Miranda, A.L.P., Fraga, C.A.M., and Barreiro. E.J., Eur.
J. Med. Chem., 2000, vol. 35, p. 187. doi org/10.1016/
S0223-5234(98)80008-1
. Olayinka, O.A., Craig, A.O., Obinna, C.N., and
David, A.A., Bioorg. Med. Chem., 2010, vol. 18, p. 214.
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