One-pot and two-step synthesis of novel carbonylthioureas and dicarbonyldithioureas derivatives

Article abstract of DOI:10.1016/j.molstruc.2015.06.074

Abstract One-pot, two-step synthesis of several 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas and 1-(phenylene-1,4-dione)-3,3′-(substituted phenyl)-dithioureas have been successfully prepared. The structures of the synthesized compounds were con

Full text of DOI:10.1016/j.molstruc.2015.06.074

Journal of Molecular Structure 1099 (2015) 427e431
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
One-pot and two-step synthesis of novel carbonylthioureas and
dicarbonyldithioureas derivatives
,
Alireza Banaei a *, Jafar Abbasi Shiran a, Afshin Saadat b, Farnaz Fazlalizadeh Ardabili a,
Patrick McArdle c
a Department of Chemistry, Payame Noor University, P.O. Box 19395-4697, Tehran, Iran
b Department of Chemistry, Germi Branch, Islamic Azad University, Germi, Iran
c Department of Chemistry, NUI Galway, Galway, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
One-pot, two-step synthesis of several 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas and 1-
(phenylene-1,4-dione)-3,30-(substituted phenyl)-dithioureas have been successfully prepared. The
structures of the synthesized compounds were confirmed by elemental analysis, FT-IR spectroscopy and
NMR. Also the crystal structure one of these compounds was determined by X-ray crystallography. All
synthesized compounds were evaluated for antibacterial activity using Salmonella enterica (SE), Micro-
coccus luteus (ML), Bacillus subtilis (BS) and Pseudomonas aeruginosa (PS).
Received 5 April 2015
Received in revised form
23 June 2015
Accepted 24 June 2015
Available online 2 July 2015
© 2015 Elsevier B.V. All rights reserved.
Keywords:
Carbonylthioureas
Dicarbonyldithioureas
Antibacterial activity
X-ray crystallography
1. Introduction
terephthaloyl dichloride with ammonium thiocyanate followed by
an amine attack on the corresponding intermediate [8]. From our
Acylthioureas and bis-acylthioureas exhibit very useful biolog-
ical activities, such as antiviral [1], antifungal [2], herbicidal [3], and
antibacterial activities [4]; as well as cytotoxicity against cancer
cells [5]. They also have extensive use in the synthesis of various
heterocycles [6]. Hence, we set our mind to devise a novel approach
to prepare these two compounds. In this way, we succeeded in
ongoing program on the synthesis of biologically active compounds
[9], we report herein the one-pot two-step synthesis of 1-
cyclopropanecarbonyl-3-(substituted phenyl)-thioureas and 1-
(phenylene-1,4-dione)-3,30-(substituted phenyl)-dithioureas using
any procedure amine, NH4SCN and corresponding acyl chloride. In
addition the crystal structure of compound 1c (Scheme 1) have
been determined by X-ray crystallography.
achieving
a
simple procedure for the synthesis of 1-
cyclopropanecarbonyl-3-(substituted phenyl)-thioureas and 1-
(phenylene-1,4-dione)-3,30-(substituted phenyl)-dithioure de-
rivatives via a one-pot, two-step process, without the need for work
up and purification of intermediates.
2. Experimental
2.1. Instrument
Due to their paramount importance, numerous methods have
been offered towards the synthesis of acylthioureas and dicarbonyl
dithioureas. In 2011, H. Peng et al. reported the synthesis of 1,3-
benzenedicarbonyl and investigated its cytotoxic properties [7].
Yusof et al. have also prepared a series of acylthioureas in a process
consisting of two steps: Preparation of cyclopropanecarbonyl iso-
thiocyanate and benzene-1,4-dioyl diisothiocyanate as in-
termediates of the reaction between cyclopropoyl chloride and
All commercially available chemicals and reagents were used
without further purification. Melting points were determined with
an Electrothermal model 9100 apparatus and are uncorrected. FTIR
spectra were recorded on a Shimadzu 8400S Spectrophotometer.
The NMR spectra were recorded on a Bruker AVANCE DMX400
spectrometer, operating at 400 MHz (1H NMR). The chemical shift
values are expressed in ppm relative toTMS as an internal standard.
Elemental analyses were recorded with CHN model 2400 Per-
kineElmer and agreed with the calculated values. The crystal
structure of compound 1c was solved by direct methods and
refined by full matrix least squares using SHELXL-97, SHELX
* Corresponding author.
E-mail address: banaei@pnu.ac.ir (A. Banaei).
http://dx.doi.org/10.1016/j.molstruc.2015.06.074
0022-2860/© 2015 Elsevier B.V. All rights reserved.

428
A. Banaei et al. / Journal of Molecular Structure 1099 (2015) 427e431
Scheme 1. One-pot, two-step synthesis of 1-cyclopropanecarbonyl-3-(substituted phenyl)-thiourea.
operations were automated using ORTEX, which was also used to
obtain the drawings [10e12]. Data were corrected for Lorentz and
polarization effects but not for absorption. The nonhydrogen atoms
were refined anisotropically. The data were collected on a Marre-
search image plate using monochromatized Mo Ka radiation
(0.71069Aꢀ) at 298 K.
C13H16N2SO3 (280.34): C, 55.70; H, 5.75; N, 9.99. Found: C, 56.03; H,
6.03; N, 10.06%. FTIR (KBr, cmꢁ1); nmax 3232, 3192, 3039, 2943,
2833, 1680, 1600, 1544, 1514, 1396, 1271, 1236, 1176, 1159, 1026, 945,
844, 727, 675, 607. 1H NMR (CDCl3, 400 MHz): dH
(ppm) ¼ 0.95ꢁ1.00 (m, 2H), 1.11e1.15 (m, 2H), 1.66e1.72 (m, 1H),
3.87 (s, 3H), 3.88 (s, 3H), 6.86 (d, 1H, J ¼ 8.4 Hz), 7.08 (dd, 1H, J ¼ 2.4,
8.4 Hz), 7.22 (d, 1H, J ¼ 2.4 Hz), 10.01 (1H, NH), 12.38 (1H, NH). 13
C
NMR (CDCl3, 100 MHz): dC (ppm) ¼ 10.0, 15.5, 55.9, 56.0, 108.5,
2.2. General procedure for synthesis of 1-cyclopropanecarbonyl-3-
(substituted phenyl) thiourea(1aei)
110.7, 116.7, 130.5, 147.7, 148.7, 175.4, 178.4.
To a solution of cyclopropyl chloride (2 mmol) in acetone 5 mL
NH4SCN (2 mmol) was added. The reaction mixture was stirred for
20e40 min at room temperature to afford a yellow or white colored
solid. After appearance of the precipitate, without further purifi-
cation, appropriate aromatic amine (2 mmol) was added to the
reaction mixture and it was stirred for another 1e2 h. The residue
was filtered, washed with Et2O and ethanol and dried at room
temperature.
2.2.5. 1-cyclopropanecarbonyl-3-(m-hydroxyphenyl)thiourea (1e)
Yield 87%. Yellowish solid. m.p.: 158e168 ꢀC. Anal.Calcd for
C11H12N2SO2 (236.29): C, 55.91; H, 5.12; N,11.86. Found: C, 55.61; H,
5.69; N, 11.07%. FTIR (KBr, cmꢁ1); nmax 3296, 3055, 3012, 1687, 1604,
1570, 1492, 1398, 1350, 1282, 1188, 1155, 939, 773, 678, 667, 501. 1H
NMR (CDCl3, 400 MHz): dH (ppm) ¼ 0.92ꢁ0.97 (m, 4H), 2.07e2.11
(m, 1H), 6.63 (dd, 1H, J ¼ 2.0, 8.0 Hz), 6.95 (dd, 1H, J ¼ 1.2, 8.0 Hz),
7.16 (t, 1H, J ¼ 8.0 Hz), 7.21 (t, 1H, J ¼ 2 Hz), 9.62 (1H, OH), 11.74 (1H,
NH), 12.50 (1H, NH). 13C NMR (CDCl3, 100 MHz): dC (ppm) ¼ 9.7,
14.6, 111.1, 113.7, 114.7, 129.9, 139.1, 157.9, 176.3, 178.4.
2.2.1. 1-cyclopropanecarbonyl-3-(p-methylphenyl)thiourea (1a)
Yield: 90%. Yellowish solid. m.p.: 136e138 ꢀC. Anal.Calcd for
C
12H14N2SO (234.32): C, 61.51; H, 6.02; N, 11.96. Found: C, 61.42; H,
2.2.6. 1-cyclopropanecarbonyl-3-(p-methoxyphenyl)thiourea (1f)
Yield 82%. White solid. m.p.: 134e136 ꢀC. Anal.Calcd for
C12H14N2SO2 (250.318): C, 57.58; H, 5.64; N, 11.19. Found: C, 58.60;
H, 5.87; N, 10.63%. FTIR (KBr, cmꢁ1); nmax 3207, 3038, 2959, 2096,
1737, 1586, 1485, 1308, 1241, 1116, 1020, 903, 524, 507. 1H NMR
(CDCl3, 400 MHz): dH (ppm) ¼ 0.95ꢁ1.04 (m, 2H), 1.1e1.114 (m, 2H),
1.65e1.72 (m, 1H), 3.89, (s, 3H), 7.03 (d, 2H, J ¼ 8.4 Hz), 7.27 (d, 2H,
J ¼ 8.4 Hz) 11.66 (1H, NH), 12.43 (1H, NH). 13C NMR (CDCl3,
100 MHz): dC (ppm) ¼ 9.5, 13.6, 58, 115.2, 126.6, 131.8, 158.2, 177.5,
179.2.
6.07; N, 11.86%. FTIR (KBr, cmꢁ1); nmax 3196, 3037, 1687, 1606, 1560,
1533, 1512, 1390, 1355, 1240, 1157, 1095, 1033, 927, 817, 723, 505. 1H
NMR (CDCl3, 400 MHz): dH (ppm) ¼ 0.98ꢁ1.03 (m, 2H), 1.13e1.17
(m, 2H), 1.67e1.73 (m, 1H), 2.37 (s, 3H), 7.21 (d, 2H, J ¼ 8.4 Hz), 7.47
(d, 2H, J ¼ 8.4 Hz), 9.96 (1H, NH), 12.40 (1H, NH). 13C NMR (CDCl3,
100 MHz): dC (ppm) ¼ 10.0, 15.5, 21.1, 124.5, 129.5, 134.9, 136.9,
175.4, 178.5.
2.2.2. 1-cyclopropanecarbonyl-3-(p-ethylphenyl)thiourea (1b)
Yield 86%. Yellowish solid. m.p.: 115e117 ꢀC. Anal.Calcd for
C
13H16N2SO (248.34): C, 62.87; H, 6.49; N, 11.28. Found: C, 62.79; H,
2.2.7. 1-cyclopropanecarbonyl-3-(m-methoxyphenyl)thiourea (1g)
Yield 86%. White solid. m.p.: 147e149 ꢀC. Anal.Calcd for
6.64; N, 11.34%. FTIR (KBr, cmꢁ1); nmax 3190, 2968, 1683, 1589, 1525,
1390, 1328, 1249, 1153, 1035, 927, 837, 725, 532. 1H NMR (CDCl3,
400 MHz): dH (ppm) ¼ 1.00ꢁ1.04 (m, 2H), 1.14e1.18 (m, 2H), 1.25 (t,
3H, J ¼ 7.6 Hz), 1.61e1.66 (m,1H), 2.67 (q, 2H, J ¼ 7.6 Hz), 7.24 (d, 2H,
C12H14N2SO2 (250.32): C, 57.58; H, 5.64; N, 11.19. Found: C, 58.61; H,
5.69; N, 10.67%. FTIR (KBr, cmꢁ1); nmax 3207, 2966, 2098, 1735, 1590,
1479, 1313, 1250, 1121, 1024, 910, 520, 507. 1H NMR (CDCl3,
400 MHz): dH (ppm) ¼ 0.95ꢁ1.04 (m, 2H), 1.1e1.114 (m, 2H),
1.65e1.72 (m, 1H), 3.93 (s, 3H), 7.01 (m, 2H, J ¼ 7 Hz),7.10 (m, 1H,
J ¼ 3.24 Hz), 7.28 (d, 1H, J ¼ 1.2 Hz), 10.97 (1H, NH), 11.88 (1H, NH).
13C NMR (CDCl3, 100 MHz): dC (ppm) ¼ 9.4, 13.5, 58.2, 115.1, 117.3,
126.3, 131.9, 139.5, 158.2, 177.5, 179.2.
J ¼ 8.4 Hz), 7.52 (d, 2H, J ¼ 8.8 Hz), 9.57 (1H, NH), 12.38 (1H, NH). 13
C
NMR (CDCl3, 100 MHz): dC (ppm) ¼ 9.9, 15.4, 15.7, 28.4, 124.3, 128.2,
135.1, 143.1, 175.0, 178.2.
2.2.3. 1-cyclopropanecarbonyl-3-(p-ethoxyphenyl)thiourea (1c)
Yield 88%. Yellowish solid; m.p.: 153e155 ꢀC. Anal.Calcd for
C
13H16N2SO2 (264.309): C, 59.07; H, 6.10; N, 10.60. Found: C, 58.98;
2.2.8. 1-cyclopropanecarbonyl-3-(3,4,5-trimethoxyphenyl)thiourea
(1h)
H, 6.17; N, 10.65%. FTIR (KBr, cmꢁ1); nmax 3201, 3035, 2985, 2920,
2870,1693,1610,1570,1539,1510,1390,1357,1257,1232,1157,1095,
1053, 929, 823, 723, 615, 516. 1H NMR (CDCl3, 400 MHz): dH
(ppm) ¼ 0.99ꢁ1.03 (m, 2H), 1.13e1.17 (m, 2H), 1.43 (t, 3H,
J ¼ 6.8 Hz), 1.61e1.66 (m, 1H), 4.04 (q, 2H, J ¼ 6.8 Hz), 6.91 (d, 2H,
J ¼ 8.8 Hz), 7.48 (d, 2H, J ¼ 8.8 Hz0), 9.64 (1H, NH), 12.28 (1H, NH).
13C NMR (CDCl3, 100 MHz): dC (ppm) ¼ 9.9, 14.8, 15.6, 63.6, 114.5,
125.9, 130.2, 157.6, 175.4, 178.5 ppm.
Yield 87%. White solid. m.p.: 161e163 ꢀC. Anal.Calcd for
C14H18N2SO4 (310.37): C, 54.18; H, 5.84; N, 9.02. Found: C, 54.26; H,
5.77; N, 8.94%. FTIR (KBr, cmꢁ1); nmax 3204, 3063, 2929, 2108, 1745,
1669, 1554, 1452, 1364, 1244, 1190, 1064, 927. 1H NMR (CDCl3,
400 MHz): dH (ppm) ¼ 0.95ꢁ1.04 (m, 2H), 1.1e1.114 (m, 2H),
1.65e1.72 (m, 1H), 3.94 (s, 3H), 3.96 (s, 6H), 6.89 (s, 2H), 11.13 (1H,
NH), 12.24 (1H, NH). 13C NMR (CDCl3, 100 MHz): dC (ppm) ¼ 9.4,
13.4, 56.5, 56.8, 104.5, 129.3, 133.9, 179.9, 180.5 182.7.
2.2.4. 1-cyclopropanecarbonyl-3-(3,4-dimethoxylphenyl)thiourea
(1d)
2.2.9. 1-cyclopropanecarbonyl-3-(1-naphthyl)thiourea (1i)
Yield 90%. White solid. m.p.: 137e139 ꢀC. Anal.Calcd for
Yield 75%. White solid. m.p.: 186e188 ꢀC. Anal.Calcd for

A. Banaei et al. / Journal of Molecular Structure 1099 (2015) 427e431
429
C15H14N2SO (270.35): C, 66.64; H, 5.22; N, 10.36. Found: C, 66.67; H,
2.3.4. 1-(Phenylene-1,4-dione)-3,30-bis(p-ethoxyphenyl)dithiourea
5.17; N, 10.33%. FTIR (KBr, cmꢁ1); nmax 3174, 3057, 2963, 2118, 1699,
1685,1627,1598, 1531,1390,1207,1184,1153, 1085, 945, 771, 478. 1H
NMR (CDCl3, 400 MHz): dH (ppm) ¼ 0.97ꢁ1.01 (m, 2H), 1.18e1.22
(m, 2H), 1.72 (m, 1H), 7.57e7.63 (m, 3H), 7.85e7.89 (d, 1H,
J ¼ 8.0 Hz), 7.91e7.96 (t, 2H, J ¼ 7.2 Hz), 7.97e8.0 (d, 1H, J ¼ 0.8 Hz),
10.27 (s,1H, NH), 12.69 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): dc
(ppm) ¼ 10.1, 15.6, 121.8, 124.1, 125.2, 126.4, 126.9, 128.0, 128.6,
128.6, 133.5, 134.1, 175.7, 180.2.
(2d)
Yield 87%; yellow solid; mp. 242e244 ꢀC. Anal.Calcd for
C26H26N4S2O4 (522.64): C, 59.75; H, 5.01; N, 10.72. Found: C, 59.72;
H, 5.04; N, 10.75%. FTIR (KBr, cmꢁ1); nmax 3396, 3049, 2980, 2926,
1670, 1614, 1560, 1508, 1475, 1301, 1247, 1147, 1010, 827, 592; 1H
NMR (DMSO, 400 MHz): dH: 1.34 (t, 6H, J ¼ 7.2 Hz), 4.04 (q, 4H,
J ¼ 7.2 Hz), 6.97 (d, 4H, J ¼ 8.8 Hz), 7.56 (d, 4H, J ¼ 8.8 Hz), 8.08 (s,
4H), 11.73 (s, 2H, NH), 12.35 (s, 2H, NH) ppm; 13C NMR (DMSO,
100 MHz): dc: 15.1, 63.7, 114.7, 126.3, 129.0, 131.1, 136.4, 157.2, 167.8,
179.3 ppm.
2.3. General procedure for the synthesis of 1-(phenylene-1,4-
dione)-3,30-bis(substituted phenyl)dithioureas (2aee)
2.3.5. 1-(Phenylene-1,4-dione)-3,30-bis(m-hydroxyphenyl)
dithiourea (2e)
The target compounds were synthesized similarly, from
(1 mmol) terephthaloyl dichloride, (2 mmol) of NH4SCN and
(2 mmol) of corresponding aromatic amine.
Yield 87%; white solid; m.p. 270e272 ꢀC. Anal.Calcd for
C22H18N4S2O4 (466.53): C, 56.64; H, 3.89; N, 12.01. Found: C, 56.67;
H, 3.91; N, 11.97%. FTIR (KBr, cmꢁ1); nmax 3340, 3130, 3039, 2937,
1674, 1600, 1539, 1489, 1338, 1286, 1178, 1124, 1016, 894, 773,
686;1H NMR (DMSO, 400 MHz): dH: 6.69 (d, 2H, J ¼ 8.0 Hz), 7.07 (d,
2H, J ¼ 7.6 Hz), 7.21 (t, 2H J ¼ 8.0 Hz), 7.28 (s, 2H), 8.07 (s, 4H), 9.72
(s, 2H, OH), 11.73 (s, 2H, NH), 12.46 (s, 2H, NH) ppm; 13C NMR
(DMSO, 100 MHz): dc: 111.3, 113.9, 114.9, 129.0, 129.9, 136.4, 139.3,
158.0, 167.8, 178.8 ppm.
2.3.1. 1-(Phenylene-1,4-dione)-3,30-bis(naphthyl)dithiourea (2a)
Yield 79%; yellow solid; mp. 257e259 ꢀC. Anal.Calcd for
C
30H22N4S2O2 (534.65): C, 67.39; H, 4.15; N, 10.48. Found: C, 67.42;
H, 4.11; N, 10.44%. FTIR (KBr, cmꢁ1); nmax 3327, 3070, 2925, 2850,
1660, 1592, 1515, 1408, 1020;1H NMR (DMSO, 400 MHz): dH:
7.59e7.63 (m, 6H), 7.83 (d, 2H, J ¼ 7.2 Hz), 7.95 (d, 2H, J ¼ 8.4 Hz),
8.02 (m, 4H), 8.20 (s, 4H), 11.98 (s, 2H, NH), 12.60 (s, 2H, NH) ppm;
13C NMR (DMSO, 100 MHz): dc: 122.7, 125.1, 125.9, 126.8, 127.2,
127.9, 128.8, 129.1, 129.2, 134.2, 134.7, 136.5, 168.1, 181.4 ppm.
2.4. Antibacterial activity determination
Bacterial isolates were grown on 3 mL of nutrient broth medium
(Merck), at 37 ꢀC, over-night. Nutrient agar (Merck) plates were
aseptically inoculated with 50 ml of bacterial culture, spread over
the surface of the plate using a sterile glass spreader. Sterile Pasteur
pipette ends were used to bore wells in to the agar. Each well was
filled with 40
2.3.2. 1-(Phenylene-1,4-dione)-3,30-bis(p-ethylphenyl)dithiourea
(2b)
Yield 77%; yellow solid; mp ¼ 243ꢁ245 ꢀC. Anal.Calcd for
C
26H26N4S2O2 (490.64): C, 63.65; H, 5.34; N, 11.42. Found: C, 63.62;
ml of the appropriate compound (final concentration
H, 5.36; N, 11.44%.FTIR (KBr, cmꢁ1); nmax 3446, 3047, 2930, 2860,
1698, 1635, 1560, 1508, 1458, 1398, 1076, 1031, 788, 574;1H NMR
(DMSO, 400 MHz): dH: 1.20 (t, 6H, J ¼ 7.2 Hz), 2.63 (q, 4H, J ¼ 7.2 Hz),
7.26 (d, 4H, J ¼ 8.4 Hz), 7.59 (d, 4H, J ¼ 8.4 Hz), 8.08 (S, 4 h), 11.73 (s,
2H, NH),12.45 (s, 2H, NH) ppm; 13C NMR (DMSO,100 MHz): dc: 15.9,
28.2, 124.7, 128.4, 129.0, 136.0, 136.4, 142.5, 167.8, 179.2 ppm.
4.38
m
g/well) and the plates were incubated for 18e24 h at 37 ꢀC.
The zones of growth inhibition were measured. All media were
prepared according to manufacturer's instructions.
3. Results and discussion
3.1. Spectroscopic characterization of compounds
2.3.3. 1-(Phenylene-1,4-dione)-3,30-bis(p-methoxyphenyl)
dithiourea (2c)
The synthetic strategies adopted for the synthesis of the target
compounds are depicted in Schemes 1 and 2. In Scheme 1, the re-
action between cyclopropylchloride with NH4SCN, in acetone as
solvent, afforded cyclopropylisothiocyanate as intermediate; sub-
sequent addition of amine to the reaction mixture produced com-
pounds 1aei. Treatment of terephthaloyl dichloride with NH4SCN
furnished benzene-1,4-dioyl diisothiocyanate. Compounds 2aee
were prepared by reacting benzene-1,4-dioyl diisothiocyanate with
amines. The synthetic pathway is given in Scheme 2. Survey of
Yield 82%; yellowish solid; mp ¼ 263ꢁ265 ꢀC, Anal.Calcd for
C
24H22N4S2O4 (494.59): C, 58.28; H, 4.48; N, 11.33. Found: C, 58.32;
H, 4.50; N, 11.29%. FTIR (KBr, cmꢁ1); nmax 3382, 3020, 2925, 2865,
1670,1596, 1505, 1430, 1250, 1150, 1077, 1060, 590;1H NMR (DMSO,
400 MHz): dH: 3.86 (s, 6H), 6.99 (d, 4H, J ¼ 8.8 Hz), 7.52e7.59 (d, 4H,
J ¼ 8.8 Hz), 8.08 (s, 4H), 11.75 (s, 2H, NH), 12.35 (s, 2H, NH) ppm; 13
C
NMR (DMSO, 100 MHz): dc: 55.7, 114.3, 122.5, 126.4, 129.0, 136.4,
159.9, 167.8, 179.4 ppm.
Scheme 2. One-pot, two-step synthesis of 1-(phenylene-1,4-dione)-3,30-(substituted phenyl)-dithiourea.

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A. Banaei et al. / Journal of Molecular Structure 1099 (2015) 427e431
Table 1
Crystallographic data of the compound 1c.
Form
1c
Empirical formula
Formula weight
Temperature
Wavelength
Crystal system
Space group
C13 H16 N2 O2 S
264.34
293.0(2) K
0.71073 Å
Monoclinic
P 21/n
Unit cell dimensions
a ¼ 8.9531(8) Å
b ¼ 6.4708(4) Å
c ¼ 22.9101(12) Å
a
b
g
¼ 90ꢀ
¼ 91.051(6)ꢀ
¼ 90ꢀ
Fig. 2. Representation of hydrogen bonded (dashed blue lines) in the crystal structures
of 1c. (For interpretation of the references to color in this figure legend, the reader is
referred to the web version of this article.)
Volume
Z
1327.06(15) Å3
4
Density (calculated)
Absorption coefficient
F(000)
Crystal size
Theta range for data collection
Index ranges
1.323 Mg/m3
0.240 mmꢁ1
Table 3
Hydrogen bonds for 1c.
560
0.50 ꢂ 0.20 ꢂ 0.15 mm3
3.271e29.192ꢀ
ꢁ12 ꢃ hꢃ11
D-H…A
d(D-H)
d(H…A)
d(D…A)
<(DHA)
C(3)-H(3)…S1#1
C(7)-H(7)…S1
C(10)-H(10)…O(1)#2
N(2)-H(1N1)…O(1)
N(1)-H(1N2)…S1#1
0.98
0.93
0.93
0.79(3)
0.87(2)
2.80
2.59
2.62
1.90(3)
2.60(2)
3.665(2)
3.244(2)
3.261(2)
2.608(2)
3.4473(18)
147.2
127.7
126.7
149(2)
164(2)
ꢁ8 ꢃ kꢃ7
ꢁ30 ꢃ lꢃ27
Reflections collected
6544
Independent reflections
Completeness to theta ¼ 25.242ꢀ
Absorption correction
Max. and min. transmission
Refinement method
3073 [R(int) ¼ 0.0215]
99.9%
Semi-empirical from equivalents
1.00000 and 0.81900
Full-matrix least-squares on F2
3073/0/176
solvents resulted in choosing acetone as the superior solvent to
CH2Cl2 and ethanol. The structures of compounds 1aei and 2aee
were fully confirmed by spectral (1H NMR, 13C NMR, IR) and
elemental analyses. The characteristic features of the 1H NMR
spectra of 1a, for instance, were the appearance of cyclopropyl
Data/restraints/parameters
Goodness-of-fit on F2
1.053
Final R indices [I > 2sigma(I)]
R indices (all data)
Extinction coefficient
R1 ¼ 0.0487, wR2 ¼ 0.1126
R1 ¼ 0.0717, wR2 ¼ 0.1259
n/a
Largest diff. peak and hole
0.273 and ꢁ0.302 e.Åꢁ3
protons at d 0.98e1.03 (m, 2H), 1.13e1.17 (m, 2H) and 1.67e1.73 (m,
1H), and nitrogen protons at 9.96 (1H, NH) and 12.40 (1H, NH) ppm.
The IR spectrum of 1a showed absorption bands due to the NH at
3196 cm-1 and the C]O group at 1678 cmꢁ1
.
Table 2
Experimental geometrical parameters for the 1c.
3.2. X-ray crystallography
Bond lengths (Å)
S1-C(5)
O(2)-C(9)
O(2)-C(12)
N(1)-C(4)
N(1)-C(5)
N(1)-H(1N2)
O(1)-C(4)
1.672(2)
1.364(2)
1.429(2)
1.374(2)
1.398(2)
0.87(2)
C(2)-C(3)
C(3)-H(3)
C(7)-C(8)
C(12)-C(13)
N(2)-C(5)
N(2)-C(6)
N(2)-H(1N1)
1.498(3)
0.9800
Single crystals of compound 1-cyclopropanecarbonyl-3-(p-
ethoxyphenyl)thiourea (1c) was obtained from a solution of
ethanol after slow evaporation at room temperature. The crystal
data and the details of the X-ray analysis are given in Table 1,
selected bond lengths and angles in Table 2. Molecular structure of
this compound is shown in Fig. 1. The bond lengths N1eC4
(1.374 Å), N2eC5 (1.323(2) Å) and N1eC5 (1.398(2) Å) are shorter
than the normal CeN (1.472 Å) bond length indicate of partial
double bond character [9]. These can be attributed to the presence
of resonance in this fragment agreement with the literature [13,14]
1.385(3)
1.501(3)
1.323(2)
1.414(2)
0.79(3)
1.224(2)
Bond angles (ꢀ)
C(9)-O(2)-C(12)
C(4)-N(1)-C(5)
C(4)-N(1)-H(1N2)
C(5)-N(1)-H(1N2)
C(5)-N(2)-C(6)
C(5)-N(2)-H(1N1)
C(6)-N(2)-H(1N1)
C(2)-C(1)-C(3)
C(2)-C(1)-H(1A)
118.10(15)
128.46(16)
117.3(15)
114.2(15)
133.21(18)
111.1(18)
115.7(18)
60.77(14)
117.7
C(1)-C(2)-C(3)
C(4)-C(3)-C(2)
C(4)-C(3)-C(1)
C(2)-C(3)-C(1)
C(4)-C(3)-H(3)
O(1)-C(4)-N(1)
N(1)-C(4)-C(3)
N(2)-C(5)-N(1)
N(2)-C(5)-S1
61.12(15)
117.98(17)
116.88(18)
58.10(14)
117.0
122.42(18)
115.29(16)
114.36(17)
127.44(16)
and forming
a planar six-membered ring with N1eH1…O1
hydrogen bond. In crystal structure of compound 1c, the torsion
Fig. 1. Displacement ellipsoid plot and atom labeling for the 1c.
Fig. 3. Illustration of R11(6), R44(4), R11(4) and R22(6). graph sets in the 1c.

A. Banaei et al. / Journal of Molecular Structure 1099 (2015) 427e431
431
Table 4
Antibacterial activity of synthesized compounds.
Compound
Conc. of compound
mg/well
Antimicrobial activity (Zone of inhibition in mm)
S. enterica
M. luteus
B. subtilis
P. aeruginosa
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2b
2c
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
14
13 0.43
13 0.86
9
9
0.76
0.43
e
e
e
e
e
8
5
0.89
0.88
10 1.04
10 0.44
9
7
e
0.88
9
0.88
12 1.4
10 0.9
14 0.87
1.2
e
e
11 1.2
16 0.58
e
e
9
e
0.46
11 0.66
e
8
6
9
8
1.2
0.87
1.2
11 0.56
e
e
8
9
0.33
0.33
6
6
0.57
0.44
13 0.87
10 0.87
e
1.6
e
11 0.57
0.72
11 0.6
10 0.86
1.5
11 0.45
0.87
15 0.56
9
e
0.66
0.65
2d
2e
Stda
Stdb
9
8
e
9
13 0.85
9
16 0.88
6
7
0.85
0.9
9
10 1.1
13 0.42
0.65
30
(ꢁ): No activity.
The inhibition zones were reported as mean SE.
a
Tetracycline was used as standard.
Erythromycin was used as standard.
b
angels, namely C5eN1eC4eC3 (179.93) and C5eN2eC6eH11
(175.79) were strong indications of planarity of the central thiourea
moiety (S1/C5/N1/N2) with cyclopropane (C1eC3) and p-ethox-
yphenyl (C6eC13) groups. In the crystal lattice, the molecules are
linked by intermolecular hydrogen bonds (Fig. 2) C(3)-H(3)…S1,
C(7)-H(7)…S1, C(10)-H(10)…O(1), N(2)-H(1N1)…O(1) and N(1)-
H(1N2)…S1 Table 3. These interactions usually produce different
kinds of cyclic motifs R11(6), R44(4), R11(4) and R22(6). Where the RYX(Z)
graph-set notation is descriptive of a Z-membered ring produced by
X hydrogen bonds between Y donoreacceptor units [15]. The two
R11(6) motifs are formed through a N2eH…O1 and C7eH7…S1
hydrogen bonds with donor-acceptor distance of 1.90 and 2.59 Å,
respectively, while the R44(4) and R11(4) rings are built via N1eH…S1
hydrogen bonds with different distance of 2.598 and 2.634 Å.
Another type of R22(6) ring forming by cooperation of N1eH…S1
and C3eH3…S1 hydrogen bonds with distance of 2.598 and 2.801 Å
respectively, is observed for 1c compound (Fig. 3).
noteworthy that the type of solvent is important in producing
target compounds. Further investigations of this compounds sys-
tem are now under cytotoxicity evaluation. The X-ray crystallog-
raphy of 1c shows R11(6), R44(4), R11(4) and R22(6) motifs in the
monomers are connected to each other via N2eH…O1, C7eH7…S1,
N1eH…S1 and C3eH3…S1 hydrogen bonds.
Acknowledgments
We are thankful to University of Ardabil Payamenoor, for the
partial financial support of this work.
Supplementary information
CCDC 1020440 contains the supplementary crystallographic
data for 1c. This data can be obtained free of charge via http://www.
Ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge
Crystallographic Data Centre, 12Union Road, Cambridge CB2 1EZ,
UK. Fax: þ44 1223 336 033; or e-mail: deposit@ccdc.cam.ac.uk.
3.3. Antibacterial activity
The results from antibacterial tests are shown in Table 4. As can
be seen, the newly synthesized compounds exhibit tangible anti-
bacterial activity. The level of activity against Salmonella enterica
and Micrococcus luteus was higher than that shown for Bacillus
subtilis and Pseudomonas aeruginosa. This is probably due to the fact
that the latter two bacteria are generally more resistant to anti-
bacterial compounds. In addition, compounds with OH group
(compounds 1e and 2e) seem to be more effective. This may be due
to the more polar nature of this group, which favors a stronger
interaction or hydrogen bonding with the cell wall components of
the bacterium. It is also worth noting that despite the lower con-
centrations of the synthesized compounds, their activity is com-
parable to the activity of the antibiotics used as standards.
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4. Conclusion
Various carbonylthiourea1a-i and dicarbonyldithiourea 2aee
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