Synthesis, characterization of some new 1-aroyl-3-(4-aminosulfonylphenyl) thioureas and crystal structure of 1-(3,4,5-trimethoxybenzoyl)- 3-(4-aminosulfonylphenyl)thiourea

Article abstract of DOI:10.1080/17415993.2010.541461

A small library of novel 1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives was synthesized by the reaction of sulfanilamide with substituted aroyl isothiocyanates in dry acetonitrile. The scope of the reaction was indicated by the synthesis of 1-undecanoyl-3-(4-aminosulfonylphenyl)thiourea, an acyl derivative involving alkanoyl isothiocyanate. All the compounds have been characterized by analytical and spectroscopic methods and in one case by single-crystal X-ray diffraction data.

Full text of DOI:10.1080/17415993.2010.541461

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Synthesis, characterization
of some new 1-aroyl-3-(4-
aminosulfonylphenyl)thioureas
and crystal structure of 1-
(3,4,5-trimethoxybenzoyl)- 3-(4-
aminosulfonylphenyl)thiourea
Aamer Saeed a , Amara Mumtaz a & H. Ishida b
a Department of Chemistry, Quaid-I-Azam University, Islamabad,
45320, Pakistan
b Department of Chemistry, Faculty of Science, Okayama
University, Okayama, 700-8530, Japan
Published online: 28 Jan 2011.
To cite this article: Aamer Saeed , Amara Mumtaz & H. Ishida (2011) Synthesis, characterization
of some new 1-aroyl-3-(4-aminosulfonylphenyl)thioureas and crystal structure of 1-(3,4,5-
trimethoxybenzoyl)- 3-(4-aminosulfonylphenyl)thiourea, Journal of Sulfur Chemistry, 32:1, 45-54,
DOI: 10.1080/17415993.2010.541461
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Journal of Sulfur Chemistry
Vol. 32, No. 1, February 2011, 45–54
Synthesis, characterization of some new
1-aroyl-3-(4-aminosulfonylphenyl)thioureas and
crystal structure of 1-(3,4,5-trimethoxybenzoyl)-
3-(4-aminosulfonylphenyl)thiourea
Aamer Saeeda*, Amara Mumtaza and H. Ishidab
aDepartment of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan; bDepartment of
Chemistry, Faculty of Science, Okayama University, Okayama 700-8530, Japan
(Received 23 August 2010; final version received 16 November 2010)
A small library of novel 1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives was synthesized by the
reaction of sulfanilamide with substituted aroyl isothiocyanates in dry acetonitrile. The scope of the
reaction was indicated by the synthesis of 1-undecanoyl-3-(4-aminosulfonylphenyl)thiourea, an acyl
derivative involving alkanoyl isothiocyanate. All the compounds have been characterized by analytical
and spectroscopic methods and in one case by single-crystal X-ray diffraction data.
NH2
S
O
O
O
R
N
C
S
O
S
R
H
H2N
NH2
N
NH
O
O
S
Keywords: 1-aroyl-3-(4-aminosulfonylphenyl)thioureas; sulfonamides; aryl/acyl isothiocyanates
1. Introduction
Since its first synthesis in 1908, sulfanilamide and its derivatives have extensively been used in
chemotherapy due to their efficacy against a broad range of microorganisms. These are true
anti-metabolites as they block a specific step in the biosynthetic pathway of the folic acid
important in cell division due to its structural similarity with para-aminobenzoic acid. Sulfonyl
*Corresponding author. Email: aamersaeed@yahoo.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.541461
http://www.informaworld.com

46 A. Saeed et al.
ureas are among the most familiar sulfanilamide derivatives and over 12,000 are known, some
of them being very potent hypoglycemic agents due to their ability to stimulate the release
of insulin from the pancreatic islets. Carbutamide, tolbutamide, chlorpropamide and tolaza-
mide belong to the first generation of sulfonylureas while those of second generation include
glyburide and glipizide (1–4). Besides antibacterial and hypoglycemic activities, sulfonamides
exhibit diuretic (5), anti-carbonic anhydrase (6), anti-thyroid (7) and anti-tumor activities (8).
Some other sulfonamides used as drugs include the protease inhibitor and antiretroviral fos-
amprenavir, the non-steroidal anti-inflammatory drug celecoxib and sumatriptan, used to treat
migraine headaches. Sulfonamides are found to exhibit remarkable antimalarial activity (9–11).
Thus, 4-(3,4-dichlorophenylureido)thioureidobenzenesulfonamide possessing a thiourea scaf-
fold was an effective in vitro inhibitor of carbonic anhydrase; repressed the ex vivo growth of
Plasmodium falciparum with an IC50 of 1 μM. Sulfonamides inhibit the first step of pyrimidine
nucleotide biosyntheses, that is, the carbonic anhydrase-mediate carbamoyl phosphate biosyn-
thesis, sulfonamide thus have potential for the development of novel therapies for human malaria
(12). Several antiplasmodial 7-chloro-4-aminoquinolyl-derived sulfonamides, ureas, thioureas
and amides, have been synthesized and tested against chloroquine resistant and chloroquine
sensitive P. falciparum (13).
1-Aroyl-3-arylthioureas containing both carbonyl and thiocarbonyl groups can coordinate with
metals using both sulphur and oxygen atoms; the presence of these hard and soft donor sites offer a
hugebondingpotential(13, 14).Thioureaderivativesareversatileprecursorstowardsnovelhetero-
cycles such as benzo- and naphthothiazolediones (15, 16), 3-aryl-2,5,6-triphenylpyrimidin-4-ones
Cl
Cl
SO2NH2
O
S
N
N
N
H
H
H
N
O
S
N
SO2NH2
S
N
N
N
H
H
H
R'
SO2NH2
N
R
S
N
H2N
N
H
SO2NH2
Figure 1. Some structurally related bio-active compounds.

Journal of Sulfur Chemistry 47
(17) and N-4-amino-1-aryl-5-cyano-6-oxo-1H-indeno-thiazepin-2-ylidene)-4-arylamides (18).
Thioureas exhibit potent anti-trypanosomal (19), influenza virus neuraminidase inhibitor (20),
antifungal against plant pathogenic fungi (21), herbicidal (22) and anticancer activities (23).
In light of the above literature reports, it was thought of considerable interest to synthesize title
compounds by appending the sulfanilamide moiety to thiourea nucleus in order to combine their
beneficial effects in a single structural unit with expected bioactivities, especially the antimalarial
and enzyme inhibitory activities. The aim of the synthesis is to reduce the toxicity of the parent
compound and improve the therapeutic effect. The title compounds constitute a unique class
of thioureas in which the free anilino nitrogen of sulfanilamide has been incorporated in the
thiourea nucleus in contrast to most of the known sulfonyl urea/thiourea derivatives in which the
sulfonamide amino group is a part of the urea/thiourea moiety (24, 25). Some of the structurally
related compounds are presented (Figure 1).
2. Results and discussion
A variety of aroyl isothiocyanates (1a–n) and an acyl isothiocyanate (1o) were prepared in situ by
reaction of suitably substituted acid chlorides with an equimolar quantity of potassium thiocyanate
in dry acetonitrile. Treatment of isothiocyanates with sulfanilamide (2) in acetonitrile in 1:1 molar
ratio furnished the corresponding 1-aroyl/alkanoyl-3-(4-aminosulfonyl phenyl)thioureas (3a–o)
in 80–91% yield (Scheme 1) (14).
O
O
R
H2N
S
NH2
N
C
S
O
(1a–o)
(2)
NH2
S
#
R=
3a H
O
O
3b 3-F
3c 3-Cl
3d 4-Cl
3e 4-CH3
3f 2-NO2
3g 3-NO2
3h 4-NO2
3i 3-Cl, 4-NO2
3j 4-Cl, 3-NO2
R
H
N
NH
3k 3,4-(CH3O)2
3l 3,4,5-(CH3O)3
3m 4-CH3-3,5-(CH3O)2
3n R-Ph= benzyl
3o R-Ph= C11H23
(3a–o)
O
S
Scheme 1. Synthetic pathway of 1-aroyl-3-(4-aminosulfonylphenyl)thioureas.
Typically, in the IR spectra of the aroyl substituted thiourea’s stretching vibrations attributable−to1
−1
free and associated NH at 3212–3350 cm−1, C O at 1655–1675 cm , C S at 1244–1263 cm
=
=

48 A. Saeed et al.
Table 1. Physical and IR data of 1-aroyl-3-(4-aminosulfonylphenyl)thioureas (3a–n).
Compound
R
H
Yield (%)
86
m.p. (◦C)
209–210
IR (cm−1
)
=
=
3a
3270 (NH), 1655 (C O), 1592 (C C), 1470
−
(thioamide I) 1326 (C S), 1299 (thioamide II),
1159, 1080 (thioamide III), 750 ((thioamide IV)
=
=
3b
3c
3d
3e
3f
3-F
90
87
71
64
85
85
88
143–144
240–241
190–191
210–211
178–179
190–191
180–181
3290 (NH), 1661 (C O), 1590 (C S), 1531
−
(thioamide I), 1334 (C S), 1244 (thioamide II),
1154, 1097 (thioamide III), 750 (thioamide IV)
=
=
3-Cl
3293 (NH), 1665 (C O), 1591 (C C), 1542
−
(thioamide I), 1332 (C S), 1245 (thioamide II),
1158, 1091 (thioamide III), 750 (thioamide IV)
=
=
4-Cl
3287 (NH), 1665 (C O), 1590 (C C), 1525
−
(thioamide I), 1325 (C S), 1254 (thioamide II),
1158, 1011 (thioamide III), 754 (thioamide IV)
=
=
4-CH3
2-NO2
3-NO2
4-NO2
3317 (NH), 1665 (C O), 1595 (C C), 1500
−
(thioamide I), 1334 (C S), 1263 (thioamide II),
1158, 1110 (thioamide III), 747 (thioamide IV)
=
=
3350 (NH), 1680 (C O), 1593 (C C), 1471
−
(thioamide I), 1328 (C S), 1257 (thioamide II),
1154, 1091 (thioamide III), 747 (thioamide IV)
=
=
3g
3h
3382 (NH), 1671 (C O), 1598 (C S), 1471
−
(thioamide I), 1328 (C S), 1268 (thioamide II),
1156, 1092 (thioamide III), 746 (thioamide IV)
=
=
3350 (NH), 1670 (C O), 1594 (C C), 1462
−
(thioamide I), 1326 (C S), 1257 (thioamide II),
1155, 1072 (thioamide III), 750 (thioamide I
(thioamide V)
=
=
3i
3-Cl-4-NO2
4-Cl-3-NO2
84
88
90
79
77
62
70
192–193
211–212
165–166
202–203
210–211
145–146
133–135
3350 (NH), 1670 (C O), 1594 (C C), 1465
−
(thioamide I), 1326 (C S), 1257 (thioamide II),
1155, 1079 (thioamide III), 749 (thioamide IV)
=
=
3j
3310 (NH), 1677 (C O), 1594 (C C), 1478
−
(thioamide I), 1320 (C S), 1250 (thioamide II),
1151, 1081 (thioamide III), 750 (thioamide IV)
=
=
3k
3l
3,4-(CH3O)2
3317 (NH), 1665N (C O), 1595 (C C), 1481
−
(thioamide I), 1334 (C S), 1263 (thioamide II),
1158, 1098 (thioamide III), 757 (thioamide IV)
=
=
3,4,5-(CH3O)3
4-CH3-3,5-(CH3O)2
R-Ph=Ph-CH2-
3311 (NH), 1660 (C O), 1591 (C C), 1481
−
(thioamide I), 1313 (C S), 1259 (thioamide II),
1158, 1098 (thioamide III), 756 (thioamide IV)
=
=
3m
3n
3o
3317 (NH), 1665 (C O), 1590 (C C), 1482
−
(thioamide I), 1331 (C S), 1261 (thioamide II),
1158, 1089 (thioamide III), 755 (thioamide VI)
=
=
3212 (NH), 1661 (C O), 1591 (C C), 1482
−
(thioamide I), 1334 (C S), 1263 (thioamide II),
1158, 1082 (thioamide III), 749 (thioamide IV)
3269 (NH), 2915, 2849, 1697 (C O), 1593 (C C),
1522, 1466 (thioamide I), 1309 (C S), 1263
(thioamide II), 1150, 903 (thioamide III), 753
(thioamide IV), 632
=
=
C11H23
-
−
in addition to those for the aromatic ring at 1581–1590 cm−1 could be identified; however, the pres-
ence of sulfonamido group leads to further complexity. In compounds containing the thioamide
−
=
group (HNCS), a set of fundamentals involving the N C and C S bonds are identified known as
“thioamide” bands: I, II, III and IV. These bands have a large contribution from C–N stretching
−
−
−
−
and (N H) deformation (I), C N and C S stretchings (II and III) and C S (IV) stretching and
they usually appear around 1470, 1250, 1080 and 750 cm−1, respectively (14, 26). The structures
were further supported by 1H and 13C NMR data (Tables 1 and 2). In 1H NMR, the characteristic
broad singlets at δ 9.19 and 12.76 for protons of N1 and N3, respectively, besides the signals for
aromatic protons are observed. 13C NMR showed the peaks around δ 170 and 179 for C O and
=

Journal of Sulfur Chemistry 49
Table 2. 1H NMR and 13C NMR data of the 1-aroyl-3-(4-aminosulfonylphenyl)thioureas (3a–n).
CHNS analysis
(calcd; obs.)
Compound
R
H
1H NMR (δ ppm, J Hz)
13C NMR (δ ppm)
EI-MS m/z(%)
3a
12.84 (s, 1H, NH), 11.68 179 (C S), 171 (C O),
C (50.13),
H (3.91),
335 [M+], 214
(2), 171
(32), 105
(100), 77
(11), 52 (16)
=
=
−
(s, 1H, NH), 7.1–7.6
(m, 5H, Ar), 7.62 (d,
2H, Ar, J = 5.6), 6.5
(d, 2H, Ar, J = 5.5)
139 (C N), 136
−
−
(C S), 133 (C CO),
132 (Ar), 131 (Ar), 129
(Ar), 128 (Ar), 127
N (12.53),
(19.21); C
(50.74), H (4.1),
N (12.99), S
(19.9)
(Ar), 126 (Ar), 124
(Ar), 122 (Ar), 121 (Ar)
=
=
3b
3c
3-F
12.81 (s, 1H, NH), 11.7
(s, 1H, NH), 7.9 (d,
2H, Ar, J = 6.1),
7.15 (d, 2H, Ar,
J = 6.5), 7.62 (d,
2H, Ar, J = 6.3), 6.5
(d, 2H, Ar, J = 5.9)
12.2 (s, 1H, NH), 10.9
(s, 1H, NH), 7.7 (s,
1H, Ar), 7.69 (s, 1H,
Ar), 7.62 (d, 2H,
Ar,J = 5.9), 7.4 (s,
1H, Ar), 6.9 (s, 1H,
Ar)
180 (C S), 173 (C O),
C (47.83), H
(3.42), N
353 [M+], 214
(5), 171
(37), 123
(100), 95
(44), 70 (54)
−
157 (C F), 139
−
−
(C N), 136 (C CO),
133 (Ar), 131 (Ar), 129
(Ar), 128 (Ar), 127
(11.89), S
(18.15); C
(48.1), H (3.91),
N (12.2), S
(19.1)
(Ar), 126 (Ar),124 (Ar),
122 (Ar), 121 (Ar),
=
=
3-Cl
179 (C S), 171 (C O),
C (45.46), H
(3.27), N
(11.37), S
(17.34); C
(45.88), H
(3.87), N
(11.89), S
(17.54)
369, 371
[M+], 214
(10), 171
(55), 138
(100), 111
(31), 85 (4)
−
139 (C N), 136
−
(C CO), 133 (Ar),
−
132 (C Cl), 131 (Ar),
129 (Ar), 128 (Ar),
127 (Ar), 126 (Ar),124
(Ar), 122 (Ar)
=
=
3d
4-Cl
12.8 (s, 1H, NH), 11.3
(s, 1H, NH), 7.9 (d,
2H, Ar), 7.11 (d, 2H,
Ar, J = 5.5), 7.62
(d, 2H, Ar, J = 5.9),
6.45 (d, 2H, Ar,
179 (C S), 171 (C O),
139 (C-S), 138.1
C (45.46), H
(3.27), N
(11.37), S
(17.34); C
(45.88), H
(3.87), N
(11.89), S
(17.54)
369, 371
[M+], 214
(9), 138
−
−
(C Cl), 136 (C CO),
133 (Ar), 131 (Ar),
(100), 111
(34), 85 (12)
129 (Ar), 128 (Ar),
127 (Ar), 126 (Ar),124
(Ar), 122 (Ar), 121 (Ar)
J = 4.5)
=
=
3e
4-CH3
12.2 (s, 1H, NH), 11
(s, 1H, NH), 7.62 (d,
2H, Ar, J = 5.2),
6.45 (d, 2H, Ar,
J = 5.5), 6.3 (d, 2H,
Ar, J = 5.9), 6.2 (d,
2H, Ar, J = 5.6), 2.3
(s, 3H, CH3)
179 (C S), 171 (C O),
C (51.56), H
(4.33), N
(12.03), S
(18.37); C
(52.3), H (4.88),
N (12.91), S
(18.99)
349 [M+], 214
(1), 171
(56), 119
(100), 91
(65)
−
141 (C CH3), 139
−
−
(C S), 136 (C CO),
133 (Ar), 132 (Ar),
131 (Ar), 129 (Ar),
128 (Ar), 127 (Ar),
126 (Ar), 124 (Ar),
122 (Ar), 121 (Ar), 32
(CH3)
=
=
3f
2-NO2 13.1 (s, 1H, NH), 11.9
(s, 1H, NH), 8.6 (d,
1H, Ar), 7.7 (d, H,
Ar, J = 5.6), 7.5 (d,
1H, Ar, J = 5.1), 7.5
(d, 1H, Ar, J = 5.9),
7.4 (d, 2H, Ar,
179 (C S), 171 (C O),
C (44.20), H
(3.18), N
380 [M+], 214
(6), 171
(42), 165
(33), 150
(100), 122
(11), 97 (21)
−
147 (C NO2), 139
−
−
(C S), 136.1 (C CO),
133 (Ar), 132 (Ar), 131
(Ar), 129 (Ar), 128
(14.73), S
(16.86); C
(44.92), H (3.8),
N (15.2), S
(17.1)
(Ar), 127 (Ar), 126
(Ar),124 (Ar), 122 (Ar)
J = 5.9), 6.5 (d, 2H,
Ar J = 5.3)
380 [M+], 214
(7), 171
(47), 150
(100), 122
(27), 97 (5)
=
=
3g
3-NO2 12.9 (s, 1H, NH), 11.1
(s, 1H, NH),7.7 (s,
1H, Ar), 7.69 (d, 1H,
Ar, J = 6.1), 7.67
(d, 2H, Ar, J = 5.3),
7.42 (s, d, H, Ar,
179 (C S), 171 (C O),
C (44.20), H
(3.18), N
−
146.3 (C NO2), 139
−
−
(C S), 136 (C CO),
133 (Ar), 132 (Ar), 131
(Ar), 129 (Ar), 128
(14.73), S
(16.86); C
(44.92), H (3.8),
N (15.2), S
(17.1)
(Ar), 127 (Ar), 126
(Ar),124 (Ar), 122 (Ar)
J = 5.4), 6.6 (d, 1H,
Ar, J = 5.1)
(Continued)

50 A. Saeed et al.
Table 2. Continued
CHNS analysis
(calcd; obs.)
Compound
R
1H NMR (δ ppm, J Hz)
13C NMR (δ ppm)
EI-MS m/z(%)
=
=
3h
4-NO2
12.2 (s, 1H, NH),
11 (s, 1H, NH),
7.69 (d, 2H, Ar,
J = 6.2), 6.54 (d,
2H, Ar, J = 5.2),
6.42 (d, 2H, Ar,
J = 4.9), 6.2 (d,
2H, Ar, J = 5.9)
179 (C S), 171 (C O), C (44.20), H
380 [M+], 214
(6), 171 (54),
150 (100), 122
(41), 97 (11)
150.8 (C-NO2), 139
(C-S), 136 (C-CO),
133 (Ar), 132 (Ar),
131 (Ar), 129 (Ar),
128 (Ar), 127 (Ar),
126 (Ar), 124 (Ar),
122 (Ar)
(3.18), N
(14.73), S
(16.86)
C (44.92), H (3.8),
N (15.2), S (17.1)
413, 415 [M+],
214 (19), 183
(100)
=
=
3i
3j
3-Cl-4-NO2
4-Cl-3-NO2
12.9 (s, 1H, NH), 10.7 179 (C S), 171 (C O), C (40.53), H
−
(s, 1H, NH),8.1 (s,
1H, Ar), 7.69 (d,
1H, Ar), 6.54 (d,
1H, Ar), 6.42 (d,
2H, Ar), 6.2 (d, 2H,
Ar)
144 (C NO2), 141
(2.67), N
−
−
(C Cl), 139 (C S),
(13.51), S
(15.46); C
(41.2), H (3.1),
N (13.68), S
(15.90)
−
136 (C C), 133 (Ar),
132 (Ar), 131 (Ar),
128 (Ar), 127 (Ar),
124 (Ar), 121 (Ar)
413, 415 [M+],
214 (11), 183
(100), 171 (28)
=
=
12.5 (s, 1H, NH),
11.5 (s, 1H, NH),
7.69 (d, 1H, Ar,
J = 5.7), 6.54 (d,
1H, Ar, J = 5.9),
6.42 (d, 2H, Ar,
J = 5.5), 6.2 (d,
2H, Ar, J = 5.6)
178 (C S), 172 (C O), C (40.53), H
−
144.3 (C NO2), 141
(2.67), N
−
−
(C Cl), 139 (C S),
(13.51), S
(15.46); C
(41.2), H (3.1),
N (13.68), S
(15.90)
−
136.2 (C CO), 133
(Ar), 132 (Ar), 131
(Ar), 128 (Ar), 127
(Ar), 124 (Ar), 122
(Ar), 121 (Ar)
=
=
3k
3,4-(OCH3)2 12.87 (s, 1H, NH),
11.68 ((s, 1H, NH),
7.9 (s, 1H, Ar), 7.88
(s, 2H, Ar), 6.7 (d,
1H, Ar, J = 5.9),
6.6 (d, 1H, Ar,
179 (C S), 171 (C O), C (52.87), H (4.71) 395 [M+], 214
−
141 (C OCH3),
N (11.56), S
(17.64); C
(53.1), H (4.77)
N (11.72), S
(17.89)
(53), 165
(100), 137 (42)
−
139 (C S), 138
−
(C OCH3), 136.1
−
(C CO), 133 (Ar),
132 (Ar), 131 (Ar),
129 (Ar), 128 (Ar),
127 (Ar), 126 (Ar),
121 (Ar), 65 (OCH3)
J = 6.1), 6.5 (s,
2H, Ar), 3.9 (s, 6H,
OCH3)
=
=
3l
3,4,5-(OCH3)3 12.87 (s, 1H, NH),
11.68 (s, 1H, NH),
7.9 (s, 2H, Ar), 7.88
(s, 2H, Ar), 6.5 (s,
2H, Ar), 3.9 (s, 9H,
OCH3)
179 (C S), 171 (C O), C (48.60), H
425 [M+], 214
(48), 195
(100), 166 (11)
−
147 (C OCH3),
(4.33), N
−
141 (C OCH3),
139 (C S), 136.3
(10.63), S
(16.22); C
(49.20), H
(4.77), N (11.3),
S (16.87)
−
−
(C CO), 133 (Ar),
132 (Ar), 131 (Ar),
129 (Ar), 128 (Ar),
127 (Ar), 126 (Ar), 65
(OCH3)
=
3m
4-CH3-3,5-
(OCH3)2
12.82 (s, 1H, NH),
11.7 (s, 1H, NH),
7.9 (s, 2H, Ar), 7.88
(s, 2H, Ar), 6.5 (s,
2H, Ar), 3.9 (s, 6H,
OCH3), 2.52 (s, 3H,
CH3)
180 (C S), 170
C (48.60), H
(4.33), N
(10.63), S
(16.22); C
(49.20), H
(4.77), N (11.3),
S (16.87)
409 [M+], 214
(21), 179
(100), 171
=
(C O), 141 (OCH3),
−
139 (C S), 136.1
(C CO), 133 (Ar),
132 (Ar), 131 (Ar),
129 (Ar), 128 (Ar),
127 (Ar), 126 (Ar),
−
(45), 151 (17)
−
116 (C CH3), 65
(OCH3), 21.3 (CH3)
349 [M+], 214
(8), 171 (52),
91 (100)
=
=
=
3n
R-Ph Ph-
CH2
12.9 (s, 1H, NH),
11.7 (s, 1H, NH),
7.1–7.6 (m, 5H,
Ar), 7.62 (d, 2H, Ar,
J = 6.2), 6.5 (d,
2H, Ar, J = 5.9),
4.3 (s, 2H, CH2)
180 (C S), 173 (C O), C (51.56), H
−
139 (C S), 136.2
(4.33), N
−
−
(C CO), 135.4 (C C)
133 (Ar), 132 (Ar),
131 (Ar), 129 (Ar),
128 (Ar), 127 (Ar),
126 (Ar), 59 (CH2)
(12.03), S
(18.35); C
(52.1), H (4.99),
N (12.78), S
(18.8)
(Continued)

Journal of Sulfur Chemistry 51
Table 2. Continued
CHNS analysis
(calcd; obs.)
Compound
R
C
1H NMR (δ ppm, J Hz)
13C NMR (δ ppm)
EI-MS m/z(%)
413 [M+], 230
(35), 171 (52),
91 (100)
=
=
=
3o
R-Ph
11H23
-
12.76 (s, 1H, NH),
9.03 (s, 1H, NH),
7.93 (d, 2H, Ar),
7.95 (d, 2H, Ar,
J = 6.2), 2.41 (m,
2H, CH2), 1.27 (br
s, 16H), 1.66 (m,
2H, CH2), 0.89 (t,
3H,J = 6.2), 8.74
(brs, NH2)
174 (C O), 182 (C S), C (55.18), H,
−
140 (C N), 136.2
(7.55) N
(10.16), S,
(15.51); C
(55.11), H
(7.46), N
(10.08), S
(15.41)
−
−
(C CO), 135.4 (C C)
133 (Ar), 131 (Ar),
33.9 (C1ꢀ), 32.0 (C9ꢀ),
29.74, 29.72, 29.6,
29.55, 29.51, 29.4
ꢀ
ꢀ
−
(C4 C8 ), 26.9
(C2ꢀ), 24.7 (C3ꢀ), 22.8
(C10ꢀ), 14.2 (C11ꢀ)
=
C S, respectively (13, 14), except for the acyl derivative 3o where these appear at δ 174 and 182,
respectively. Table 1 gives the physical and IR data of thioureas (3a–o) while the 1H NMR and
13C NMR data are listed in Table 2.
In the mass spectra of the compounds, in addition to the molecular ion peaks, the major frag-
ments are derived from the N-McLafferty rearrangement and the base peaks originate from the
substituted benzoyl cation. The fragmentation pattern of (3l) is shown in Scheme 2.
O
-CO
N
C
S
H3CO
OCH3
H3CO
OCH3
OCH3
OCH3
H3CO
OCH3
m/z 167 (45%)
m/z 196 (100%)
OCH3
m/z 225 (7.7%)
SO2NH2
NH
O
S
N
C S
H3CO
H3CO
H3CO
H3CO
OH
N
N
H
H
N-McLafferty
m/z 425 (32%)
OCH3
m/z 226 (11%)
OCH3
SO2NH2
(3l)
m/z 213 (55%)
O
NH
N
C
S
SO2NH2
H2NO2S
m/z 172 (3%)
m/z 259 (8%)
SO2NH2
m/z 186 (17%)
Scheme 2. Mass fragmentation of 1-(3,4,5-trimethoxybenzoyl)-3-(4-aminosulfonylphenyl)
thiourea (3l).

52 A. Saeed et al.
2.1. X-ray structure
ORTEP drawing of the molecular structure of compound 3l as determined in the crystalline phase
is depicted in Figure 2.
The N-(phenylcarbamothioyl)benzamide moiety is essentially planar with a maximum devi-
ation of 0.1025(10)Å for atom C2 (Figure 2). The central N2/C7/S2/N3/C8/O3 plane makes
dihedral angles of 6.55(5)◦ and 6.45(5)◦ with benzene◦C1–C6 and C9–C14 rings, respectively. The
−
two benzene rings make a dihedral angle of 0.81(5) . In the molecule, intramolecular N H· · ·
−
O and C H· · · S hydrogen bonds are observed. In the crystal structure, the molecules are con-
−
nected by N H · · · O hydrogen bonds to afford a double chain structure running along the [10-1]
direction (Figure 3). The chains are further connected through water molecules to form a layer
expanding parallel to the (111) plane.
Figure 2. Molecular structure of 3l with the atom-numbering scheme. Displacement ellipsoids are shown at the 50%
probability level.
Figure 3. Crystal packing of 3l with intra- and intermolecular hydrogen bonding pattern indicated as dashed lines.

Journal of Sulfur Chemistry 53
3. Conclusion
Several 1-aroyl-3-(4-aminosulfonylphenyl)thioureas (3a–n) and one 1-acyl derivative (3o) have
been synthesized, which differ from most of the known sulfonyl thiourea derivatives in having
the free anilino nitrogen of sulfanilamide incorporated into the thiourea nucleus leaving the
sulfonamide amino group intact, for detailed bioevaluation and comparison.
4. Experimental
4.1. Instrumentation
Melting points were recorded using a digital Gallenkamp (SANYO) model MPD.BM 3.5 appara-
tus and are uncorrected. 1H NMR spectra were determined in CDCl3 solution at 300 MHz using
a Bruker AM-300 spectrophotometer using TMS as an internal reference and 13C NMR spectra
were determined at 75 MHz using a Bruker 75 MHz NMR spectrometer in CDCl3 solution. FTIR
spectra were recorded on an FTS 3000 MX spectrophotometer. Mass spectra (EI, 70 eV) were
determined on a MAT 312 instrument, and elemental analyses were conducted using a LECO-183
CHNS analyzer.
Crystallographic data were collected on a Bruker-AXS SMART APEX CCD diffractometer.
The crystal structure was solved by direct methods. H-atoms were located from different Fourier
maps and then refined at idealized positions with the riding model.
4.2. Synthesis of 1-aroyl-3-(4-aminosulfonylphenyl)thioureas: general procedure
A solution of suitably substituted benzoyl/acyl chloride (10 mmol) in dry acetonitrile (50 ml) was
added dropwise to a suspension of potassium thiocyanate (10 mmol) in acetonitrile (30 ml) and
the reaction mixture was refluxed for 30 min to afford isothiocyanates (1a–o). After cooling to
room temperature, a solution of sulfanilamide (2) (10 mmol) in dry acetonitrile (10 ml) was added
and the resulting mixture refluxed for 1–3 h. The reaction mixture was poured into cold water and
the precipitated thioureas (3a–o) were recrystallized using aqueous ethanol. The physicochemical
and spectral data (IR, 1H, 13C NMR, EI-MS) of the products are given in Tables 1 and 2.
Supplementary material
CCDC 787098 contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif or by e-mailing
data_request@ccdc.cam.ac.uk or by contacting The Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB21EZ, UK; fax: +44 1223-336033.
Acknowledgement
A.M. gratefully acknowledges a research scholarship from HEC Islamabad under HEC Indigenous PhD Scholarship
Scheme.
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