Synthesis, characterization, crystal structures, and antibacterial activity of some new 1-(3,4,5-trimethoxybenzoyl)-3-aryl thioureas

Article abstract of DOI:10.3906/kim-0810-44

Synthesis of some novel 1-(3,4,5-trimethoxy)benzoyl-3-arylthiourea derivatives (1a-o) was accomplished in 2 steps. The synthetic route involves the reaction of 1-(3,4,5-trimethoxy)benzoyl chloride with potassium thiocyanate in 1:1 molar ratio in acetone t

Full text of DOI:10.3906/kim-0810-44

Turk J Chem
34 (2010) , 335 – 345.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0810-44
Synthesis, characterization, crystal structures, and
antibacterial activity of some new
1-(3,4,5-trimethoxybenzoyl)-3-aryl thioureas
Aamer SAEED1,∗, Rasheed Ahmad KHERA1, Naeem ABBAS1, Muhammad LATIF1,
2
3
¨
Imran SAJID and Ulrich FLORKE
1Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, PAKISTAN
e-mail: aamersaeed@yahoo.com
2Department of Microbiology, Punjab University, Lahore-PAKISTAN
3Department Chemie, Fakult¨at fur Naturwissenschaften, Universitat Paderborn,
Warburgerstrasse 100, D-33098 Paderborn-GERMANY
Received 28.10.2009
Synthesis of some novel 1-(3,4,5-trimethoxy)benzoyl-3-arylthiourea derivatives (1a-o) was accomplished
in 2 steps. The synthetic route involves the reaction of 1-(3,4,5-trimethoxy)benzoyl chloride with potassium
thiocyanate in 1:1 molar ratio in acetone to afford the corresponding isothiocyante followed by treatment
with suitably substituted anilines. The structures of the products were established by elemental analyses,
IR, 1 H- and 13 C-NMR, and mass spectroscopy and for 1b and 1m from single crystal X-ray diffraction data.
All of the synthesized compounds (1a-o) were screened for antibacterial activity against gram positive and
gram negative bacterial strains and were found to exhibit low activity towards the tested microorganisms,
compared to chloramphenicol, the standard drug.
Key Words: 1-(3,4,5-trimethoxy)benzoyl-3-arylthioureas, antibacterial, crystal structure.
Introduction
There has been considerable interest in recent years in the synthesis of various 1,3-disubstituted thioureas.1
Thiourea derivatives are exceptionally versatile building blocks for the synthesis of a variety of heterocyclic
compounds and exhibit a wide spectrum of bioactivities.2 N,N-Dialkyl-N-aroyl thioureas are efficient lig-
ands for the separation of platinum group metals.3 1,3-Dialkyl or diaryl thioureas exhibit significant an-
tifungal activity against the plant pathogens Pyricularia oryzae and Drechslera oryzae.4 N-aryl N-phenyl
∗Corresponding author
335

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
thioureas have been developed as anion-binding sites in a hydrogen-bonding receptor,5 thiacalix[4]arenes con-
taining thioureas as neutral receptors towards α,α–dicarboxylate anions,6 and N-4-substituted-benzyl-N-ter-
butylbenzyl thioureas as vanilloid receptors ligands and antagonists in rat DRG neurons.7 1-Benzoyl-3-(4,6-
disubstituted-pyrimidinyl)thioureas have shown excellent herbicidal activity.8 Acyl thioureas are well known
for their superior pesticidal, fungicidal, antiviral, and regulating activity for plant growth.9 Thioureas have
been widely used in enantioselective synthesis, such as in nitro-Mannich reactions, Aza-Henry reactions, and
the Michael addition.10−12 Symmetrical and asymmetrical phenethyl thioureas, 5-halo-substituted thiophene
pyridyl thioureas, and heterocyclic thioureas are non-nucleoside inhibitors of HIV-1 reverse transcriptase.13−15
Synthesis and anion recognition of molecular tweezers receptors based on acyl thioureas16 and efficient colori-
metric anion sensors have recently been reported.17 Moreover, thiourea analogues are potent influenza virus
neuraminidase inhibitors.18
Condensation of thiourea derivatives with carbonyl compounds has been used in the synthesis of N-alkyl-
1,3-thiazol-2-amines and 3-alkyl-1,3-thiazolimines,19 1-aroyl-3-aryl-4-substituted imidazole-2-thiones,20 and
2-(aroylimino)-3-aryl-4-methyl/phenyl-1,3-thia-zolines.21 Cyclocondensation of unsymmetrical perfluoroalkyl
substituted beta-diketones with urea, thiourea, and guanidine leads to various heterocycles.22 Regioselec-
tive synthesis of 2H-[1,2,4]thiadiazolo pyrimidine derivatives23 and 2-(9H -fluoren-9-ylmethoxy-carbonylamino)-
thiazole-4-carboxylic acids via N-Fmoc thioureas24 has recently been described.
Taking into consideration the aforementioned biological and synthetic significance of thioureas, the
synthesis of some new 1-(3,4,5-trimethoxy)benzoyl-3-arylthiourea derivatives was undertaken as precursors
towards novel heterocycles and for the systematic study of their bioactivity and complexation behavior.
Experimental
Melting points were recorded using a digital Gallenkamp (SANYO) model MPD.BM 3.5 apparatus and are
uncorrected. 1 H- and 13 C-NMR spectra were determined in CDCl3 at 300 MHz and 75 MHz, respectively,
using a Bruker spectrophotometer. FTIR spectra were recorded on an FTS 3000 MX spectrophotometer. Mass
spectra (EI, 70 eV) were recorded on a GC-MS instrument (Agilent Technologies), and elemental analyses
were conducted using a LECO-183 CHNS analyzer. Bioactivities were investigated at the Department of
Microbiology, Punjab University, Lahore, Pakistan. Thin layer chromatography (TLC) was conducted on 0.25
mm silica gel plates (60 F254, Merck). Visualization was performed with ultraviolet light. Reagents were
obtained commercially and used as received.
X-ray data collection and structure refinement
1b: C18 H20 N2 O4 S, Mr = 360.4, monoclinic, space group P21 /c, a = 11.5786(11), b = 7.1613(7), c = 21.831(2)
◦
3
A, β = 104.117(2) , V = 1755.5(3) A , Z = 4, Dx = 1.364 g/cm3 , F(000) = 760, T = 120(2) K. Bruker-AXS
˚
˚
SMART APEX CCD27 graphite monochromator, λ(MoKα) = 0.71073 A, μ = 0.21 mm−1 , colorless crystal,
˚
size 0.23 × 0.20 × 0.19 mm3 , 15,183 intensities collected 1.8 < θ < 27.9◦ , -15 < h < 15, -9 < k < 9, -28
< l < 28. Structure solved by direct methods,25 full-matrix least-squares refinement25 with 4198 independent
reflections based on F2 and 243 parameters, all but H atoms and C182 refined anisotropically. Hydrogen atoms
336

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
were located from difference Fourier maps and refined at idealized positions riding on the carbon atoms with
isotropic displacement parameters Uiso (H) = 1.2Ueq (C) or 1.5Ueq (methyl-C). H(N) atom parameters were
refined freely. The methyl group is disordered over 2 sites with site occupation factors 0.719(3) for C181 at C17
and 0.281(3) for C182 at C13. Hydrogen atoms at C13 and C17 were treated accordingly. Refinement converged
at R1(I>2σ (I)) = 0.050, wR2(all data) = 0.087, S = 0.85, max(δvσ) < 0.001, min/max height in final ΔF
3
˚
map –0.34/0.35 e/A . The molecular structure of 1b and selected bond lengths and angles are depicted in
Figure 1.
Figure 1. Molecular structure of 1b with displacement ellipsoids plotted at 50% probability level. Only major part
◦
˚
(C181) of disordered CH3 group shown. Selected bond lengths (A) and angles ( ): C2-O1 1.222(2), C2-C3 1.492(3),
C2-N1 1.388(2), N1-C1 1.395(2), C1-S1 1.669(2), C1-N2 1.325(3); C3-C2-N1 117.15(18), C2-N1-C1 126.45(18), N1-C1-N2
116.76(18), C1-N2-C12 123.82(18).
1m: C17 H24 N2 O4 S, Mr = 352.4, monoclinic, space group P21 /c, a = 12.852(3), b = 16.725(3), c =
◦
3
8.3899(17) A, β = 107.255(5) , V = 1722.2(6) A , Z = 4, Dx = 1.359 g/cm3 , F(000) = 752, T = 120(2)
˚
˚
−1
K. Bruker-AXS SMART APEX CCD,27 graphite monochromator, λ(MoKα) = 0.71073 A, μ = 0.21 mm
,
˚
colorless crystal, size 0.40 × 0.11 × 0.10 mm3 , 15,025 intensities collected 1.7 < θ < 27.9◦ , -16 < h < 16,
-21 < k < 22, -11 < l < 10. Structure solved by direct methods,25 full-matrix least-squares refinement25
with 4103 independent reflections based on F2 and 227 parameters, all but H atoms refined anisotropically.
Hydrogen atoms were located from difference Fourier maps and refined at idealized positions riding on the
carbon atoms with isotropic displacement parameters Uiso (H) = 1.2Ueq (C) or 1.5Ueq (methyl-C). H(N) atom
parameters were refined freely. Refinement converged at R1(I>2σ (I)) = 0.042, wR2(all data) = 0.107, S =
3
˚
1.02, max(δvσ) < 0.001, min/max height in final ΔF map –0.21/0.39 e/A . The molecular structure of 1m
and selected bond lengths and angles are depicted in Figure 3.
337

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
Figure 2. Crystal packing of 1b viewed along [010] with intermolecular hydrogen bonding pattern indicated as dashed
lines (N1-H. . . S1(-x+1, -y+1, -z) H-atoms not involved in hydrogen bonding are omitted. The dimers are stacked along
[001].
Figure 3. Molecular structure of 1m with displacement ellipsoids plotted at 50% probability level. Selected bond
◦
˚
lengths (A) and angles ( ): C2-O1 1.2268(19), C2-C3 1.498(2), C2-N1 1.368(2), N1-C1 1.403(2), C1-S1 1.6739(16),
C1-N2 1.325(2); C3-C2-N1 114.97(13), C2-N1-C1 128.47(13), N1-C1-N2 116.93(14), C1-N2-C12 123.13(13).
Synthesis of 1-(3,4,5-trimethoxybenzoyl)-3-aryl thioureas, general procedure
A solution of 1-(3,4,5-trimethoxy)benzoyl chloride (10 mmol) in acetone (50 mL) was added dropwise to a
suspension of potassium thiocyanate (10 mmol) in acetone (30 mL) and the reaction mixture was refluxed for
30 min. After cooling to room temperature, a solution of the substituted aniline (10 mmol) in acetone (10 mL)
338

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
was added and the resulting mixture refluxed for 2-3 h. The reaction mixture was poured into cold water and
the precipitated thioureas were recrystallized from aqueous ethanol.
The physicochemical and spectral data are given in Tables 1 and 2, respectively. All compounds gave
satisfactory elemental analyses.
Table 1. Physicochemical data of thioureas (1a-o).
Compd
Yield
(%)
70
Rfa
Mp
Molecular formula (MW)
EIMS
[M.+
(◦C)
]
1a
1b
1c
1d
1e
1f
0.47
0.45
0.46
0.27
0.25
0.48
0.47
0.49
0.51
0.53
0.28
0.26
0.54
0.56
0.58
134-135
142-143
138-139
166-167
145-146
136-137
111-112
127-128
124-125
136-137
103-107
145-146
152-153
124-125
129-130
C17H18N2O4S (346.09)
C18H18N2O4S (360.11)
C18H18N2O4S (360.11)
C18H20N2O5S (376.10)
C18H20N2O5S (376.10)
C17H17ClN2O4S (380.00)
C17H17ClN2O4S (380.00)
C17H17ClN2O4S (380.00
C17H17BrN2O4S (424.00)
C18H19ClN2O4S (394.07)
C17H17N3O6S (391.08)
C17H17N3O6S (391.08)
C17H24N2O4S (352.14)
C13H18N2O4S (298.09)
C15H22N2O4S (326.13)
346.0
360.0
360.0
376.0
376.0
380.0
380.0
380.0
424.0
394.0
391.0
391.0
352.1
298.0
326.1
65
68
72
69
72
1g
1h
1i
63
71
69
1j
68
1k
1l
62
72
1m
1n
1o
75
64
56
a Solvent system: Pet. ether: Ethyl acetate (1:0.25); Recrystallization solvent: ethanol (aq)
Results and discussion
The reaction sequence leading to the formation of thioureas is outlined in the Scheme. Commercial 1-(3,4,5-
trimethoxy)benzoic acid was converted into corresponding acid chloride by treatment with thionyl chloride
according to the standard procedure. The latter was treated with an equimolar quantity of potassium thio-
cyanate in acetone to afford the corresponding isothiocyante intermediate, which was not separated. Addition
of an equimolar quantity of substituted anilines in acetone furnished the title thiourea derivatives (1a–o).26
Typically, thioureas are characterized by IR absorptions at 3350 and 3200 for free and associated NH
respectively, at 1660-1670 for carbonyl, and at 1230-1250 cm−1 for thiocarbonyl groups. The characteristic
broad singlets at ca. δ 9.0 and 12 ppm for HN(1) and HN(2) and peaks at ca. 170 and 179 for carbonyl
and thiocarbonyl were also observed in the 1 H- and 13 C-NMR spectra, respectively. The physicochemical
properties and the spectroscopic data of thioureas 1a-o are given in Tables 1 and 2, respectively. Mass spectra
of all of the compounds showed the molecular ion peaks. The major fragments correspond to the N-McLafferty
rearrangement and the base peak is derived from the trimethoxybenzoyl cation.
339

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
Table 2. Spectral data (IR, 1 H-, 13 C-NMR) of thioureas (1a-o).
Compd
1a
IR (υ, cm−1
)
1H-NMR (δ, ppm, J(Hz)
13C-NMR (δ, ppm)
3250 (NH), 1660 (C=O), 1579 12.63 (NH), 9.15 (NH), 7.72- 56.50, 61.07, 104.94, 124.15, 126.57, 126.99,
(C=C), 1236 (C=S), 1132 (C-
N)
7.09 (m, 7H, Ar’), 3.94 (s, 9H,
OCH3).
128.95, 137.57, 142.90, 153.52, 166.77
(C=S), 178.38 (C=O).
1b
3259 (NH), 1663 (C=O), 1579 12.29 (NH), 9.22 (NH), 7.12- 18.04 (CH3), 56.52, 61.07, 105.02, 124.19,
(C=C), 1254 (C=S), 1143 (C-
N)
7.77 (m, 6H, Ar’), 3.95 (s, 9H,
OCH3), 2.34 (s, 3H, CH3).
126.17, 126.49, 127.73, 130.82, 133.27,
136.36, 142.92, 153.54, 166.79 (C=S),
179.39 (C=O).
1c
3265 (N-H), 1666 (C=O),
12.53 (NH), 9.18 (NH), 7.05- 21.12 (CH3), 56.511, 61.04, 105.25, 122.10,
1586 (C=C), 1259 (C=S), 7.59 (m, 6H, Ar’), 3.94 (s, 9H,
124.19, 126.63, 136.95, 142.91, 153.37,
166.74, 178.48 (C=S), 189.65 (C=O).
1144 (C-N).
OCH3), 2.38 (s, 3H, CH3).
1d
3223 (N-H), 1669 (C=O),
12.46 (NH), 9.13 (NH), 6.92- 55.47 (OCH3), 56.50, 61.02, 104.92, 114.0,
1587 (C=C), 1261 (C=S), 7.56 (m, 6H, Ar’), 3.94 (s, 9H,
125.73, 126.61, 127.5, 128.7, 130.5, 142.93,
153.21, 158.23, 165.63 (C=S), 178.65
(C=O).
1153 (C-N).
OCH3), 3.85 (s, 3H, OCH3).
1e
3221 (N-H), 1670 (C=O),
12.44 (NH), 9.10 (NH), 7.60- 55.49, 56.52, 61.05, 104.96, 114.14, 125.84,
1590 (C=C), 1256 (C=S), 6.95 (m, 6H, Ar’), 3.95 (s, 9H,
1153 (C-N) OCH3 ), 3.85 (s, 3H, CH3).
126.63, 127.32, 128.4, 130.53, 142.95,
153.56, 158.33, 166.66 (C=S), 178.66
(C=O).
1f
3219 (N-H), 1668 (C=O),1593 12.77 (br s, 1H, NH), 9.16 (br 56.54, 61.07, 105.07, 126.19, 126.43, 126.92,
(C=C), 1233 (C=S), 1155 (C-
N)
s, 1H, NH), 7.04 -7.51 (Ar-
Hx6), 3.96 (s, 9H, OCH3 )
127.75, 127.96, 130.3, 135.01, 143.01,
153.55, 166.48 (C=S), 178.68 (C=O).
1g
3229 (N-H), 1689 (C=O),
12.39 (br s, 1H, NH), 9.41 (br 56.43 (OCH3 ), 121.41, 125.40, 126.65,
1603 (C=C), 1246 (C=S), s, 1H, NH), 7.28 -7.76 (Ar-
127.58, 129.84, 130.61, 133.18, 133.43,
134.82, 136.13, 153.1, 166.30 (C=S), 177.92
(C=O).
1151 (C-N)
Hx6), 3.92 (s, 9H, OCH3 ).
1h
1i
3296 (N-H), 1660 (C=O),
1586 (C=C), 1238 (C=S), s, 1H, NH), 7.04 -7.65 (Ar-
1173 (C-N)
12.64 (br s, 1H, NH), 9.07 (br 56.52, 104.98, 121.52, 125.31, 126.38, 128.2,
129.06, 130.4, 136.50, 143.09, 153.34, 165.7
(C=S), 178.41 (C=O)
Hx6), 3.92 (s, 9H, OCH3 ).
3243 (N-H), 1663 (C=O),
12.65 (br s, 1H, NH), 9.13 (br 56.45, 61.07, 105.19, 120.08, 126.36, 132.03,
1587 (C=C), 1241 (C=S), s, 1H, NH), 7.28 -7.82 (Ar-
136.6, 143.09, 153.57, 162.19, 166.80, 178.39
(C=S), 189.62 (C=O).
1153 (C-N)
Hx5), 3.92 (s, 9H, OCH3 ).
1j
3285 (N-H), 1672 (C=O),
12.65 (br s, 1H, NH), 9.15 20.39 (CH3), 56.54, 61.07, 105.06, 126.17,
1586 (C=C), 1239 (C=S), (br s, 1H, NH), 6.67-8.19 (Ar-
126.49, 127.88, 128.5, 130.07, 138.32,
143.00, 153.56, 166.45 (C=S), 178.79
(C=O).
1128 (C-N)
Hx6), 3.93 (s, 9H, OCH3),
2.38 (s, 3H, CH3).
1k
1l
3297 (N-H), 1667 (C=O),
1581 (C=C), 1239 (C=S), s, 1H, NH), 7.12 -8.03 (Ar-
1134 (C-N)
12.93 (br s, 1H, NH), 10.5 (br 56.24, 60.98, 107.36, 116.92, 118.74, 124.13,
126.21, 128.3, 130.4, 135.64, 142.92, 152.96,
166.56 (C=S), 178.17 (C=O).
Hx6), 3.96 (s, 9H, OCH3 ).
3310 (N-H), 1659 (C=O),
12.94 (br s, 1H, NH), 10.7 (br 56.29, 61.06, 107.39, 116.95, 118.76, 124.15,
1574 (C=C), 1237 (C=S), s, 1H, NH), 7.05 -8.08 (Ar-
126.24, 135.66, 142.95, 152.98, 166.58
(C=S), 178.18 (C=O)
1137 (C-N)
Hx6), 3.97 (s, 9H, OCH3 ).
1m
3411 (N-H), 1657 (C=O),
10.76 (br s, 1H, NH), 8.89 (br 24.32, 24.96, 25.44, 56.46, 60.91, 104.79,
1572 (C=C), 1239 (C=S), s, 1H, NH), 7.26 (s, Ar-Hx2),
126.87, 130.66, 142.71, 153.40, 166.56
(C=S), 178.17 (C=O).
1134 (C-N)
4.25 (m, 1H), 3.92 (s, 9H,
OCH3), 1.22-2.11 (m, 10H).
1n
1o
34310 (N-H), 1657 (C=O),
1572 (C=C), 1239 (C=S), s, 1H, NH), 7.07 (s, Ar-Hx2),
1134 (C-N)
11.51 (br s, 1H, NH), 8.6 (br 43.16, 43.30, 56.41, 61.00, 105.23, 127.41,
142.24, 153.29, 163.04 (C=S), 180.14
(C=O).
3.91 (s, 9H, OCH3), 3.26 (s,
6H, CH3).
3415 (N-H), 1657 (C=O),
11.69 (br s, 1H, NH), 8.90 (br 14.6, 21.03, 32.05, 25.44, 56.41, 60.91,
47.0, 130.66, 142.06, 152.04, 168.53 (C=S),
185.01 (C=O)
1572 (C=C), 1239 (C=S), s, 1H, NH), 7.03 (s, Ar-Hx2),
1134 (C-N)
3.91 (s, 9H, OCH3), 3.40 (t,
2H), 1.60 (m, 2H, Hx2), 1.36
(m, 2H), 1.06 (t, 3H, Hx3).
340

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
Scheme. Synthesis of some new 1 (3,4,5-trimethoxybenzoyl)-3-aryl thioureas.
Antibacterial activity
The synthesized compounds were screened for their antibacterial activities against pathogenic bacteria such as
avian pathogenic E. coli (APEC), Staphylococcus aureus, Pseudomonas sp., Klebsella sp., Bacillus subtilis, and
Salmonella paratyphae using disk diffusion method (Kirby-Bauer method). The test compounds were dissolved
in methanol at a concentration of 1 μg/μL using chloramphenicol was used as a standard drug.27 The tests
were repeated 3 times and the results are reported as means of at least 3 determinations. The results are
summarized in Table 3. The figures represent the zone of inhibition in millimeters. As is evident from the table
all compounds (1a-j) exhibited in general low inhibitory activity against the 6 strains compared to the standard
drug at the tested concentration. Most of them are active against B. subtilus and Klebsella spp., while for the
rest of the strains only 1 or 2 compounds showed activity.
Geometric parameters for 1b (Figure 1) and 1m (Figure 3) display C=S and C=O double bonds as
˚
well as shortened C-N bonds (range 1.325(2) to 1.403(2) A), which is typical for these thiourea units. The
substitution of benzene (1b) with the cyclohexyl ring (1m) leads to slight elongation of the N2-C12 bond from
˚
1.441(3) to 1.469(2) A.
The torsion angles C1-N1-C2-O1 of –5.2(3)◦ and C2-N1-C1-N2 of –7.6(3)◦ for 1b and of -8.0(3)◦ and
of 3.7(2)◦ for 1m, respectively, reflect the almost planar conformations with respect to the carbonyl and
341

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
thiocarbonyl parts. The trimethoxybenzene ring planes and the C2-O1-N1 planes form dihedral angles of
25.1(2)◦ for 1b and 37.1(2)◦ for 1m. For both structures the 2 methoxy groups O2 and O4 lie almost in plane
with the aromatic ring, whereas the O3 groups are oriented perpendicular with C5-C6-O3-C10 of 92.4(2)◦ (1b)
and C5-C7-O3-C8 of 110.6(2)◦ (1m).
Table 3. Antibacterial bioassay screening of thioureas (1a-o).
Compound
APEC Staphylococcus Pseudomonas Klebsella
Bacillus Salmonella
subtilis paratyphae
aureus
sp.
sp.
-
1a
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1b
–
-
10
11
+
-
1c
-
7
-
1d
-
-
1e
11
+
-
-
7
-
-
1f
-
10
12
11
-
-
1g
-
-
1h
-
12
-
-
-
1i
10
-
-
-
9
-
1j
-
11
10
-
-
1k
+
-
7
-
+
-
10
10
10
10
+
30
-
1l
-
1m
-
-
-
-
-
-
1n
1o
+
-
-
-
-
-
-
-
Chloremphenicol
30
20
20
28
24
Diameter of inhibition (5 mm)
APEC = Avian pathogenic E. coli
Concentration used: 1 μg/μL
Volume loaded in each well = 50 μL
(weight of the sample in each well is 50 μg)
(-) = no activity
(+) = significant activity around the well
(
) = minor zone of inhibition
In the crystal structure of 1b, intermolecular N1–H...S(-x+1, -y+1, -z) hydrogen bonds with H· · ·S
◦
˚
2.52 A, N–H· · ·S 161.1 link molecules into centrosymmetric dimers, which are stacked along [010] (Figure 2).
◦
˚
Similarly in 1m intermolecular N1–H· · ·O3(-x, -y, -z+2) hydrogen bonds with H· · ·O 2.16 A, N–H· · ·O 152.8
link molecules into centrosymmetric dimers as well (Figure 4). The intramolecular N2–H· · ·O1 interactions for
both structures are common features.
342

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
Figure 4. Crystal packing of 1m viewed along [001] with intermolecular hydrogen bonding pattern indicated as dashed
lines (N1-H.. . O3(-x, -y, -z+2). H-atoms not involved in hydrogen bonding are omitted. The dimers are stacked along
[010].
Supplementary material
Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystal-
lographic Data Centre. Copies of the data CCDC-703773 (1b) and 703774 (1m) can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [e-mail: deposit@ccdc.cam.ac.uk].
343

Synthesis, characterization, crystal structures, and antibacterial..., A. SAEED, et al.,
Acknowledgement
N.A. gratefully acknowledges a research scholarship from HEC Islamabad under HEC Indigenous PhD Schol-
arship 5000 Scheme.
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