Synthesis, supramolecular structure, antimicrobial and plant-growth regulation activities of n-benzoylthiourea

Article abstract of DOI:10.14233/ajchem.2014.15784

N-Benzoylthiourea has been synthesized and characterized by elemental analysis, IR and 1H NMR etc. The X-ray crystallography of the compound indicates that the carbonyl group forms an intramolecular hydrogen bond with the N2-H2 group, which forms a six-membered ring (C7/N1/C8/N2/H2/O1) srtucture. Each molecule are linked by the intermolecular N2-H2A...S2 and N4-H4A...S1 hydrogen bonds to form a dimer, adjacent dimers are linked by the intermolecular N1-H1N...S2 and N3-H3N...S1 hydrogen bonds, leading to a hydrogenbonded netty structure. The results indicated that the N-benzoylthiourea played the important role in plant-growth regulators and may be a potential source of active antimicrobial agents.

Full text of DOI:10.14233/ajchem.2014.15784

Asian Journal of Chemistry; Vol. 26, No. 1 (2014), 237-240
http://dx.doi.org/10.14233/ajchem.2014.15784
Synthesis, Supramolecular Structure, Antimicrobial and
Plant-Growth Regulation Activities of N-Benzoylthiourea
*
MENG-MENG ZHAO, XIU-YAN DONG , YU-HUA YANG, GANG LI and YU-JIE ZHANG
School of Chemical and Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, P.R. China
*
Corresponding author: E-mail: dxy568@163.com
Received: 16 May 2013; Accepted: 18 July 2013;
Published online: 26 December 2013;
AJC-14513
1
N-Benzoylthiourea has been synthesized and characterized by elemental analysis, IR and H NMR etc. The X-ray crystallography of the
compound indicates that the carbonyl group forms an intramolecular hydrogen bond with the N2-H2 group, which forms a six-membered
ring (C7/N1/C8/N2/H2/O1) srtucture. Each molecule are linked by the intermolecular N2-H2A...S2 and N4-H4A...S1 hydrogen bonds to
form a dimer, adjacent dimers are linked by the intermolecular N1-H1N...S2 and N3-H3N...S1 hydrogen bonds, leading to a hydrogen-
bonded netty structure. The results indicated that the N-benzoylthiourea played the important role in plant-growth regulators and may be
a potential source of active antimicrobial agents.
Keywords: Thiourea, Synthesis, Crystal structure, Antibacterial, Plant-growth regulation activity.
-
1
4
00 cm was recorded with a VERTEX70 FT-IR spectropho-
INTRODUCTION
1
tometer using KBr pellets. H NMR spectrum was determined
by German Bruker AVANCE DRX-400 spectrometers with
TMS as internal standard and d -DMSO as solvent. X-ray
Thiourea and its derivatives, especially acylthiourea, are
extensively studied because of their biological activities such
as herbicides, insecticides, plant-growth regulators, antifungal,
6
single crystal structure determination was obtained on a Rigaku
RAXIS-RAPID detector. Melting points were obtained by use
of a X4 microscopic melting point apparatus made in Beijing
Taike instrument limited company and were uncorrected.
The antimicrobial activities were determined using agar
disc diffusion method by measuring the inhibition zone in mm.
All organisms were obtained from the China Center of Indus-
trial Culture Collection, including 2 bacterial stains: Escherichia
coli ACCC11864 as gram-negative bacteria, Bacillus subtilis
ACCC 01518 as gram-positive bacteria, 4 fungal stains:
Botrytis cinerea ACCC35153, Thanatephorus cucumeris
ACCC30367, Phyricularia griseaACCC100762 and Fusarium
oxysporum ACCC13422. Ampicillin and fluconazole were
served as standard antibacterial and antifungal agents, respec-
tively. The plant growth regulation activities were determined
using in vitro plate method. The seeds of rape were brought
from Seed store.
1
-5
antibacterial and pharmacodynamics . Some thioureas are
organic reaction catalyst in the metal-catalyzed asymmetric
reduction of carbonyl compounds and carbonylative cyclization
6,7
of o-hydroxyarylacetylenes . With the rapid development of
supramolecular chemistry, thioureas are one of many important
neutral receptors because of their anion recognition properties
8-10
,
H-atom of thiourea group N-H bond form easily hydrogen
bond, which recognize the anion by the interaction of the
13
hydrogen bond and the anion. In a C NMR study, the diffe-
rences between the benzoyl (CO) chemical shift value of
N-monosubstituted and N,N-disubstituted indicated the
existence of an intramolecular hydrogen bond, namely between
the benzoyl (CO) and the N-H group. The indication was also
1
11
supported by the H NMR spectrum . Here we report synthesis
and crystal structure of N-benzoylthiourea, C OS. Then
H
8 8
N
2
tested it possessed prominent antimicrobial and plant growth
regulation activities.
General procedure
EXPERIMENTAL
Synthesis of N-benzoylthiourea: Benzoyl chloride (1.41
All chemicals were of analytical reagent grade and were
used without further purification. C, H and N analyses were
obtained using a GmbH VarioEL V3.00 automatic elemental
analysis instrument. The IR spectrum in the range of 4000-
g, 10 mmol) was reacted with ammonium thiocyanate (1.14
g, 15 mmol) in CH
2
Cl (25 ml) solution under soild-liquid
2
phase transfer catalysis, using polyethylene glycol-400 (0.18
g) as the catalyst, to give the corresponding benzoyl isothiocyanate.

238 Zhao et al.
Asian J. Chem.
O
NH2
O
O
C
C
PEG-400 / CH Cl2
NH ·H O /CHCl
2
3
2
3
C
C
NH SCN
S
+
4
N
H
room temp.
Heat
Cl
N=C=S
Scheme-I: Synthetic scheme of the title compound.
The resulting mixture was evaporated to dryness using a rotatory
evaporator and the residue was extracted with chloroform, to
give the title compound.Yield 84.6 %. m.p. 386-388 K. Anal.
using the program.All hydrogen atoms were added theoretically.
The final refinements converged at R
1
= 0.0289, wR
2
= 0.0850
2
2
2
2
with ω = 1/[σ (F
o
) + (0.0526P) + 0.2490P], where P = (F +
o
2
Calcd. (%) for C
8
H
8
N
2
OS: C, 53.31; H,4.47; N, 15.54. Found
2F
c
)/3. All atoms were refined with anisotropic displacement
-1
(
%): C, 53.23; H, 4.58; N, 15.32. Selected IR data (cm , KBr
parameters. The largest differential peak and hole were 0.359
1
-3
pellet): 3310, 3225(νNH), 1680(νC=O) and 1031(νC=S). H NMR
400 MHz, CDCl , δ, ppm): 7.53-7.87 (m, 5H,Ar-H), 9.98 (s,
H, HN), 10.06 (s, 2H, H2N).
Colorless needle-shaped single crystals were obtained by
and -0.277 e Å . The structural plots were drawn with SHELXL
1
2
(
3
97 software package . The crystal data and experimental
parameters relevant to the structure determination are listed in
Table-1.
1
slow evaporation of an chloroform solution after several weeks
at room temperature. Synthetic scheme of the title compound
was shown in Scheme-I.
Antimicrobial activity: The culture media used were
nutrient agar and Sabourd's medium for bacteria and fungus
strains, respectively. The hot nutrient agar and sabourd's
medium solution was poured into sterilized petridishes and
allowed to attain room temperature. Seed layer medium which
contains the previously grown subculture was lawned into the
Petri dishes. Cups were made using sterile borer of 5 mm
diameter. To these cups 0.5 mL of the drug solution (50 µg/mL),
standard solution were added and allowed to cool for 1 h to
facilitate diffusion. The plate was incubated at 37 °C or 28 °C
for 48 h. Zone of inhibition around wells were measured. All
tests were repeated three times to confirm the results. The
results are presented in Table-2.
X-ray structure determination: The colorless crystal
with a dimension of 0.67 mm × 0.48 mm × 0.13 mm was
placed on a Rigaku RAXIS-RAPID detector. Intensity data
were collected with a graphite-monochromator MoKα radia-
tion (λ = 0.71073 Å) at 153(2) K. The structure was solved by
2
direct methods and refined by full matrix least squares on F
TABLE-1
CRYSTAL DATA AND STRUCTURE REFINEMENT
FOR THE TITLE COMPOUND
Plant-growth regulators determination: The method of
vitro plate was adopted. Twain's 80 was used as emulsifier,
the compound was dissolved in the solution of N,N-dimethyl-
formamide. Six kinds of solution were configurated with
distilled water respectively (100, 10, 01.0, 0.1, 0.01, 0.001
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
C H N OS
8 8 2
180.22
153(2)
0.71073
Triclinic
P-1
a = 8.1862(4), b = 9.2399(5),
c = 12.4921(8), α = 73.509(2),
Space group
Cell dimensions, (Å, deg)
-1
mg L ). Put 10 mL solution with differents concentration into
9
mm culture plate (including 2 layers of filter paper), use
equivalent emulsifier as contrast. 15-20 healthy seeds of
Brassica napus were choosen and puted into every plate, The
plates were incubated at 25 ± 5 °C for 72 h. Then for day light
8 h every day, examined after 5 d. Measured the growth of the
root and the stem, calculated the percentage of plant growth
regulator activity.
β = 87.766(2), γ = 70.556(2)
852.74(8)
4
1.404
0.329
376
3
Volume (Å )
Z
3
Density (calculated) (mg/m )
Absorption coefficient (mm )
-
1
F(000)
Index ranges
-10 ≤ h ≤ 10, -11 ≤ k ≤ 11, -16
The promotion rate (the inhibition rate) = (N-N
1
)/N
1
×
≤
l ≤ 16
1
00 %. N : The average of the length of rape root in distill
1
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness of fit indicator
R [I > 2σ(I)]
8370/3864 [R(int) = 0.0205]
3566
3864/0/242
0.996
water, N: The average of the length of rape root in compound
solution All tests were repeated three times to confirm the
results. The results are presented in Table-3.
R = 0.0289, wR = 0.0850
1
2
-
3
Largest diff. peak and hole (e Å ) 0.359 and -0.277
TABLE-2
RESULTS OF ANTITUBERCULOSIS AND ANTIMICROBIAL ACTIVITIES FOR THE TITLE COMPOUND
Diameter of zone of inhibition (mm)
Compound
B. subtilis
8.9 ± 0.25
10.3 ± 0.3
–
E. coli
B. cinerea
T. cucumeris
12.9 ± 0.2
–
P. grisea
10.4 ± 0.35
–
F. oxysporum
7.8 ± 0.15
–
N-Benzoylthiourea
Ampicillin
Fluconazole
–
12.6 ± 0.5
–
11.4 ± 0.35
13.2 ± 0.6
14.9 ± 0.55
15.4 ± 0.6
14.2 ± 0.65
(
– indicates no activity).

Vol. 26, No. 1 (2014)
Synthesis, Antimicrobial and Plant-Growth Regulation Activities of N-Benzoylthiourea 239
TABLE-3
DATA OF PLANT GROWTH REGULATION ACTIVITY OF
TARGET FOR THE TITLE COMPOUND
-1
C (mg L )
.001
.01
Indolylacetic acid
4.5 ± 0.1
6.9 ± 0.12
-12.5 ± 0.23
-62.1 ± 0.3
-85.9 ± 1.2
-98.1 ± 3.1
N-Benzoylthiourea
-19.8 ± 0.11
-22.0 ± 0.24
-39.3 ± 0.6
0
0
0.1
1.0
-11.7 ± 0.25
-37.5 ± 0.4
-73.6 ± 0.31
10
100
RESULTS AND DISCUSSION
Description of crystal structure: Selected bond lengths
and angles are listed in Table-4. The data for hydrogen bonds
are given in Table-5. The molecular structure with atom
label1ing, two-dimensional mono-layer structure and its pack-
ing diagram along c-axis were shown in Figs. 1-3, respectively.
Fig. 2. The two-dimensional mono-layer netty structure. Hydrogen bonds
are illustrated by dashed line
Fig. 3. Three-dimensional packing diagram of the title compound, H atoms
are omitted for clarity
Fig. 1. Crystal structure and atom numbering of the title compound
the N2-H2 group, which forms a six-membered ring (C7/N1/
C8/N2/H2/O1) srtucture. This is similar to that found in
N-benzoyl-N'-(3-pyridyl)thiourea . The C=O bond length
is 1.22(3) Å, longer than the normal C=O bond length (1.20(3)
Å), which is due to intramolecular hydrogen bond. The bond
The crystal structure of the title compound is built up by
1
3,14
only the C
8
H
8
N OS molecules. X-ray crystallographic analysis
2
revealed the crystal structure of N-benzoylthiourea, which the
carbonyl group forms an intramolecular hydrogen bond with
TABLE-4
SELECTED BOND DISTANCES (Å) AND ANGLES (º) FOR THE TITLE COMPOUND
Bond
S1-C8
O1-C7
N1-C8
N1-C7
Lengths
1.685(1)
1.220(1)
1.382(1)
1.384(1)
Angles
Bond
N2-C8
C1-C2
C1-C6
C2-C3
Lengths
1.314(2)
1.385(2)
1.392(2)
1.385(2)
Angles
Bond
C3-C4
C4-C5
C5-C6
C6-C7
Lengths
1.384(2)
1.392(2)
1.391(2)
1.491(2)
Angles
Bond
Bond
Bond
C8-N1-C7
C2-C1-C6
C1-C2-C3
C4-C3-C2
C3-C4-C5
126.9(1)
120.12(1)
119.9(1)
120.2(1)
120.2(1)
C6-C5-C4
C5-C6-C1
C5-C6-C7
C1-C6-C7
O1-C7-N1
119.6(1)
119.9(1)
121.9(1)
18.1(1)
O1-C7-C6
N1-C7-C6
N2-C8-N1
N2-C8-S1
N1-C8-S1
122.2(1)
114.7(1)
118.3(1)
123.45(9)
118.25(8)
123.0(1)
TABLE-5
DATA FOR HYDROGEN-BONDING INTERACTIONS (Å, º)
D-H···A
d(D-H)
d(H···A)
d(D···A)
∠D-H···A
176
Symmetry code
N1-H1N...S2
N3-H3N...S1
N2-H2B...O1
N2-H2A...S2
N4-H4B...O2
N4-H4A...S1
0.89
0.91
0.86
0.87
0.87
0.88
2.47
2.50
2.03
2.61
1.95
2.41
3.353(1)
3.401(1)
2.664(2)
3.447(1)
2.621(2)
3.282(2)
x, y, z
x, y, z
x, y, z
1 + x, y, z
x, y, z
-1 + x, y, z
174
131
164
132
173

240 Zhao et al.
Asian J. Chem.
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intermolecular hydrogen bonds H1N...S2, H3N...S1, H2A...S2,
H4A...S1 are 2.47(2), 2.50(2), 3.56(2) and 2.41(2) Å, respec-
tively. Fig. 2 is shown that four distinct hydrogen bonds occur
in the crystal structure: which each pair molecules are linked
by the intermolecular N2-H2A...S2 (-x+1, -y, -z+1), N4-
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.
Antimicrobial and plant-growth regulation activities:
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