3-Mercaptopropionic acid-nitrile imine adducts. An unprecedented cyclization into 1,3,4-thiadiazol-2(3H)-ones and -2(3H)-thiones

Article abstract of DOI:10.1039/b505010c

3-Mercaptopropionic acid-nitrile imine acyclic adducts (6a-c) undergo cyclocondensation with 1,1'-carbonyldiimidazole to afford the respective 1,3,4-thiadiazol-2-(3H)-ones (7a-c). Corresponding 1,3,4-thiadiazol-2(3AT)-thiones (8a-c) were likwise produced

Full text of DOI:10.1039/b505010c

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A R T I C L E
3-Mercaptopropionic acid–nitrile imine adducts. An unprecedented
cyclization into 1,3,4-thiadiazol-2(3H)-ones and -2(3H)-thiones
Jalal A. Zahra,a Bassam A. Abu Thaher,b Mustafa M. El-Abadelah*a and Roland Boesec
a Chemistry Department, Faculty of Science, University of Jordan, Amman, Jordan.
E-mail: mustelab@ju.edu.jo; Fax: 00962 6 534 8932
b Chemistry Department, Faculty of Science, Islamic University of Gaza, Gaza Strip
c Institut fu¨r Anorganische Chemie, Universita¨t Duisburg-Essen, Campus Essen
Universita¨tstrasse 3–5, D-45117, Essen, Germany
Received 12th April 2005, Accepted 13th May 2005
First published as an Advance Article on the web 13th June 2005
3-Mercaptopropionic acid–nitrile imine acyclic adducts (6a–c) undergo cyclocondensation with
1,1ꢀ-carbonyldiimidazole to afford the respective 1,3,4-thiadiazol-2-(3H)-ones (7a–c). Corresponding
1,3,4-thiadiazol-2(3H)-thiones (8a–c) were likwise produced from 6a–c and 1,1ꢀ-thiocarbonyldiimidazole, with
consequent elimination of the propionate moiety. The constitution of these heterocyclic products follows from
analytical and spectral data and is confirmed by single crystal X-ray structure determination for 7b.
employed in placement of CDI. Hence, the present work
Introduction
deals with this unprecedented transformation mode of 6 as
a new synthetic route towards 1,3,4-thiadiazol-2(3H)-ones (7)
and the respective -2(3H)-thiones (8), for which a plausible
mechanistic pathway is postulated (Scheme 3). In this context,
it is worth noting that the chemistry and bio-properties of 1,3,4-
thiadiazoles received considerable interest and the subject was
occasionally reviewed.3
Recently we have reported on an unique transformation of 2-
mercaptobenzoic acid–nitrile imine adducts (1), induced by 1,1ꢀ-
carbonyldiimidazole (CDI) into the corresponding 2-(arylhydra
zono)-1-benzothiophene-3-ones (3) (Scheme 1).1 Likewise, CDI-
induced cyclocondensation of 2-mercaptonicotinic acid-nitrile
imine adducts (2) gave the corresponding 2-(arylhydrazono)-3-
oxothieno[2,3-b]pyridines (4).2
Results and discussion
3-Mercaptopropionic acid, acting as a strong sulfur nucleophile
in basic medium, readily adds to nitrile imines (the reactive 1,3-
dipolar species, generated in situ from their N-arylhydrazonoyl
chloride precursors (5a–c)4,5 in the presence of triethylamine) to
produce the corresponding 3-[(2-oxo-1-arylhydrazonopropan-
1-yl)mercapto]propanoic acids (6a–c, Scheme 2). The constitu-
tion of the latter acyclic adducts (6a–c) is based on elemental
analyses, IR, MS and NMR spectral data that are given in the
Experimental section. 1H- and 13C-signal assignments followed
from DEPT and 2D (COSY, HMQC and HMBC) experiments.
The a- and b-methylene carbon atoms in 6a–c resonate at ca. 28
and 29 ppm, respectively, while their methylene hydrogens give
rise to two distinct triplets centered at ca. 2.5 and 3.0 ppm.
Surprisingly, these methylene 1H-/13C-resonances are not
observed in the NMR spectra of the corresponding cyclized
products, isolated from the reaction of 6a–c with CDI. This
fact implies the loss of the a- and b-methylene groups in 6a–c
during the cyclization process and thus excludes the formation of
the anticipated structure 9 (Scheme 2). Eventually, the cyclized
products of 6a–c/CDI were identified as 5-acetyl-3-aryl-1,3,4-
thiadiazol-2-(3H)-ones 7a–c, as evidenced from their elemental
Scheme 1
Following this route, we envisaged that the related 3-mer-
captopropionic acid–nitrile imine acyclic adducts (6), under
similar conditions, would produce the respective 2-(arylhydra-
zono)dihydrothiophen-3-ones (9, Scheme 2). However, this ex-
pectation was not realized in this study. Instead, the main isolable
products from 6a–c and CDI were identified as 5-acetyl-3-aryl-
1,3,4-thiadiazol-2(3H)-ones (7a–c, Scheme 2). Interestingly, the
corresponding -2(3H)-thiones (8a–c) were obtained from the
respective 6a–c when 1,1ꢀ-thiocarbonyldiimidazole (TCDI) was
1
analyses, IR, MS, H- and 13C-NMR spectral data, given in
the Experimental section, and confirmed by single crystal X-ray
structure determination for 7b (Table 1, Fig. 1and Fig. 2).†
On the other hand, activation of 6a–c with TCDI led to the
formation of the corresponding 1,3,4-thiadiazol-2(3H)-thiones
(8a–c, Scheme 2), while none of 7a–c was detected therein. This
result indicates that the endocyclic 2-thione group in 8a–c comes
from 1,1ꢀ-thiocarbonyldiimidazole and that, by inference, the
2-one entity in 7a–c originates from 1,1ꢀ-carbonyldiimidazole,
and not from the carboxy group of 6a–c. These de facto results
suggest that the carboxy group is also eliminated from 6a–c,
together with the a- and b-methylenes (as gaseous CO2 and
=
Scheme 2
CH2 CH2), during the cyclization process as induced by CDI
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 9 9 – 2 6 0 3
2 5 9 9
©

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Scheme 3
Fig. 1 ORTEP plot for both independent molecules of 7b.
◦
˚
Table 1 Selected bond lengths (A) and angles ( ) for 7b
Angle (◦)
˚
Bond
Length (A)
Bond
S(1)–C(2)
S(1)–C(5)
C(2)–N(3)
N(3)–N(4)
N(4)–C(5)
O(1)–C(2)
C(5)–C(6)
N(3)–C(8)
1.7772(18)
1.7321(18)
1.397(2)
1.3600(18)
1.291(2)
1.208(2)
1.486(2)
C(5)–S(1)–C(2)
O(1)–C(2)–S(1)
O(1)–C(2)–N(3)
N(4)–N(3)–C(2)
N(4)–N(3)–C(8)
C(5)–N(4)–N(3)
N(4)–C(5)–S(1)
C(6)–C(5)–S(1)
88.91(8)
125.91(15)
127.17(17)
116.74(13)
117.14(13)
111.29(14)
116.01(13)
121.39(13)
Fig. 2 Overlay of the two independent molecules, demonstrating the
different conformations.
intermediate ( Scheme 3, C). Subsequently, the aryl-NH hooks
at the nearby N-carbonyl (thiocarbonyl) carbon in C, displacing
the imidazole with consequent production of the corresponding
thiadiazole derivatives (7a–c/8a–c). The imidazole nucleus in A
probably participates cooperatively in the ‘catalytic’ nucleophilic
role of the sulfur atom that led to the expulsion of the propionate
moiety from B/C (Scheme 3).
1.437(2)
S(21)–C(22)
S(21)–C(25)
C(22)–N(23)
N(23)–N(24)
N(24)–C(25)
O(3)–C(22)
C(25)–C(26)
N(23)–C(28)
1.7765(16)
1.7312(15)
1.4005(17)
1.3616(16)
1.2936(19)
1.2058(17)
1.483(2)
C(25)–S(21)–C(22)
O(3)–C(22)–S(21)
O(3)–C(22)–N(23)
N(24)–N(23)–C(22)
N(24)–N(23)–C(28)
C(25)–N(24)–N(23)
N(24)–C(25)–S(21)
C(26)–C(25)–S(21)
88.54(7)
126.77(12)
126.12(14)
117.02(12)
118.03(11)
110.37(11)
116.92(11)
120.29(11)
1.4347(18)
Conclusion
1,3,4-Thiadiazol-2-ones (e.g. 7) are readily prepared by a two-
step reaction involving the formation of 3-mercaptopropionic
acid–nitrile imine acyclic adducts (6) and their cyclization with
CDI under mild conditions (Scheme 2). This new method com-
petes favorably with the reported route involving the preparation
of 5-imino-1,3,4-thiadiazolines (e.g. 10a) and their subsequent
two-step transformation (N-nitrosation to 11, followed by ther-
mal decomposition) into 7 (Scheme 4).6–8 Cyclization of adducts
or TCDI and for which a plausible pathway is depicted in the
annexed mechanism (Scheme 3). Intramolecular nucleophilic
attack by the sulfur atom at the suitably situated N-carbonyl
(thiocarbonyl) carbon of the mixed anhydride (Scheme 3, A) fa-
cilitates the initial displacement of the propionate anion (shown
in Scheme 3, B) and its subsequent breakdown, with the ultimate
formation of the respective thiocarbamate (dithiocarbamate)
2 6 0 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 9 9 – 2 6 0 3

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ꢀ
ꢀ
ꢀ
ꢀ
=
4 ), 129.7 (C-3 /C-5 ), 133.7 (C N), 143.4 (C-1 ), 173.4 (CO2H),
+
=
193.5 (O C–Me); HRMS (ESI): found 289.0604 (M + Na ),
C12H14N2O3SNa requires 289.0623; m/z (EI): 266 (M+, 100%),
194 (13), 160 (28), 118 (88), 92 (53), 91 (82).
3-{[1-(4-Methylphenylhydrazono)-2-oxopropan-1-
yl]mercapto}propanoic acid 6b
This compound was prepared from 3-mercaptopropionic acid
(2.1 g, 20 mmol) and 1-chloro-1-(4-methylphenylhydrazono)-
propanone (5b) (3.4 g, 16 mmol) by following the same procedure
described above for obtaining 6a. Yield 3.2 g (71%); mp 144–
145 ◦C; found C, 55.49; H, 5.66; N, 9.85; S, 11.41%. C13H16N2O3S
requires C, 55.70; H, 5.75; N, 9.99; S, 11.44.%; mmax(KBr)/cm−1
3434 br, 3183, 2997, 2925, 1703, 1634, 1513, 1441, 1226, 1203 and
1081;1H-NMR (300 MHz, DMSO-d6): d 2.22(s, 3H, Ar–CH3),
2.38 (s, 3H, CH3CO), 2.46 (t, J = 6.9 Hz, 2H, CH2CO2H), 2.92
(t, J = 6.9, Hz, 2H, CH2–S), 7.10 (d, J = 8.0 Hz, 2H, H-3ꢀ/H-5ꢀ),
7.31 (t, J = 8.0 Hz, 2H, H-2ꢀ/ H6ꢀ), 10.38 (s, 1H, NH), 12.30 (br s,
1H, CO2H);13CNMR (75 MHz, DMSO-d6): d 20.9 (CH3–Ar),
25.9 (CH3CO), 27.7 (CH2–S), 35.4 (CH2–CO2H), 115.3 (C-2ꢀ/C-
Scheme 4
(6) with TCDI followed a similar course (as for CDI9), producing
the respective 1,3,4-thiadiazol-2-thiones (8, Scheme 2) for which
other procedures, based on hydrazonoyl chlorides (e.g. 1), were
described.7,10,11
Experimental
General
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
=
6 ), 130.1 (C-3 /C-5 ), 132.0 (C-4 ), 132.9 (C N), 141.1 (C-1 ),
3-Mercaptopropionic acid, 3-chloro-2,4-pentanedione, 1,1ꢀ-
carbonyldiimidazole (CDI) and 1,1ꢀ-thiocarbonyldiimidazole
(TCDI) were purchased from Acros. Melting points (un-
corrected) were determined on a Gallenkamp electrothermal
melting temperature apparatus. 1H- and 13C -NMR spectra
were measured on a Bruker DPX-300 instrument with Me3Si
as an internal reference. EIMS spectra were obtained using
a Finnigan MAT TSQ-70 spectrometer at 70 eV; ion source
=
173.4 (CO2H), 193.4 (O C–Me); HRMS (ESI): found 303.0780
(M + Na+), C13H16N2O3SNa requires 303.0779; m/z (EI): 280
(M+, 100%), 208 (15), 174 (6), 132 (98), 106 (76), 91 (82).
3-{[1-(4-Chlorophenylhydrazono)-2-oxopropan-1-yl]mercapto}
propanoic acid 6c
◦
This compound was prepared from 3-mercaptopropionic acid
(2.1 g, 20 mmol) and 1-chloro-1-(4-chlorophenylhydrazono)-
propanone (5c) (3.7 g, 16 mmol) by following the same procedure
described above for obtaining 6a. Yield 3.1 g (65%); mp
155–156 ◦C; found C, 48.12; H, 4.50; N, 9.18; S, 10.41%.
C12H13ClN2O3S requires C, 47.92; H, 4.36; N, 9.31; S, 10.66%;
mmax(KBr)/cm−1 3441, 3410, 3178, 3120, 3094, 3074, 2999, 2931,
1702, 1645, 1595, 1514, 1455, 1408, 1362, 1324, 1230, 1089 and
1030;1H-NMR (300 MHz, DMSO-d6): d 2.39 (s, 3H, CH3), 2.46
(t, J = 6.6 Hz, 2H, CH2–CO2H), 2.95 (t, J = 6.6 Hz, 2H CH2–S),
7.41 (d, J = 8.3 Hz, 2H, H-2ꢀ/ H-6ꢀ), 7.80 (d, J = 8.3 Hz, 2H,
H-3ꢀ/ H-5ꢀ), 10.57 (s, 1H, NH), 12.34 (s, 1H, CO2H); 13C-NMR
(75 MHz, DMSO-d6): d 26.0 (CH3), 27.7 (CH2–S), 35.6 (CH2–
temperature = 200 C. High resolution MS-ESI data for 6a–c
were obtained with Bruker Bio TOF III, while HRMS data for
7a–c/8a–c were obtained with a MAT 95(S) mass spectrometer.
IR spectra were recorded as KBr discs on a Nicolet Impact-400
FT-IR spectrophotometer. Microanalyses were performed at the
Microanalytical Laboratory-Inorganic Chemistry Department,
Tu¨bingen University, Germany.
1-Arylhydrazono-1-chloropropanones 1a–c
These hydrazonoyl chlorides 5a,4,5 5b4 and 5c4,5 were previ-
ously characterized and are prepared in this study via the
Japp–Klingemann reaction,12 that involves direct coupling of
the appropriate arenediazonium chloride with 3-chloro-2,4-
pentanedione following a standard procedure.4
CO2H), 116.8 (C-2ꢀ/C-6ꢀ), 126.5 (C-4ꢀ), 129.5 (C-3ꢀ/C6ꢀ), 134.6
ꢀ
=
=
(C N), 142.5 (C-1 ), 173.5 (CO2H), 193.5 (O C–Me); HRMS
(ESI): found 323.0225 (M + Na+), C12H13ClN2O3SNa requires
323.0233; m/z (EI): 300 (M+, 84%), 228 (18), 194 (9), 152 (100),
126 (66), 111 (15).
3-{[2-Oxo-1-(phenylhydrazono)propan-1-yl]mercapto}
propanoic acid 6a
To a stirred and cooled (0 ◦C) solution of 1-chloro-1-
phenylhydrazonopropanone (5a) (3.1 g, 16 mmol) in tetrahy-
drofuran (40 cm3) was added triethylamine (11 cm3). To this
solution was immediately added dropwise a solution of 3-
mercaptopropionic acid (2.1 g, 20 mmol) in methanol–water
(47:3 v/v) containing NaOH (1.6 g). The reaction mixture was
further stirred at 0 ◦C for 20–30 min and then at rt for 3–4 h. The
organic solvents were then removed in vacuo from the reaction
mixture and the residual solution was directly acidified with
glacial acetic acid (6 cm3). Trituration of the resulting crude
gum yielded a solid product which was collected, dried and
recrystallized from methanol. Yield 2.8 g (66%); mp 133–134 ◦C;
found C, 54.22; H, 5.18; N, 10.55; S, 11.86%. C12H14N2O3S
requires C, 54.12; H, 5.30; N, 10.52; S, 12.04%; mmax(KBr)/cm−1
3440, 3413, 3150, 3100, 3002, 2959, 2926, 1724, 1635, 1600,
1524, 1463, 1428, 1358, 1325, 1288, 1233 and 1028;1H-NMR
(300 MHz, DMSO-d6): d 2.40 (s, 3H, CH3), 2.47 (t, J = 6.7 Hz,
2H, CH2CO2H), 2.94 (t, J = 6.7 Hz, 2H, CH2–S), 6.96 (t, J =
7.2 Hz, 1H, H-4ꢀ), 7.29 (dd, J = 7.9 Hz, 7.2 Hz, 2H, H-3ꢀ/ H-5ꢀ),
7.41 (d, J = 7.9 Hz, 2H, H-2ꢀ/ H-6ꢀ), 10.55 (s, 1H, NH), 12.57
(br s, 1H, CO2H); 13C-NMR (75 MHz, DMSO-d6): d 26.0 (CH3),
27.7 (CH2–S), 35.5 (CH2–CO2H), 115.3 (C-2ꢀ/C-6ꢀ), 123.0 (C-
5-Acetyl-3-phenyl-1,3,4-thiadiazol-2(3H)-one 7a
To a mixture of 1,1ꢀ-carbonyldiimidazole (2.0 g, 12.5 mmol) and
compound 6a (2.7 g, 10 mmol) was added dry tetrahydrofuran
(50 cm3) and the resulting solution was stirred at rt for 2–3 h. The
solvent was then removed in vacuo, the residue was immediately
treated with water (40 cm3) and extracted with chloroform (2 ×
40 cm3). The combined organic extracts were dried (Na2SO4),
the solvent was evaporated and the residual solid product was
rec◦rystallized from hot methanol. Yield 1.3 g (59%); mp 72–
73 C (lit.6 57 ◦C); found C, 54.33; H, 3.58; N, 12.61; S, 14.52%.
C10H8N2O2S requires C, 54.53; H, 3.66; N, 12.72; S, 14.56%;
mmax(KBr)/cm−1 3113, 3068, 3010, 2965, 2920, 1692 br, 1654,
1592, 1527, 1487, 1418, 1362, 1274 br, 1144, 1089 and 1018;1H-
NMR (300 MHz, DMSO-d6): d 2.53 (s, 3H, CH3), 7.42 (t, J =
7.3 Hz, 1H, H-4ꢀ), 7.52 (dd, J = 8.2 Hz, 7.3 Hz, H-3ꢀ/H-5ꢀ), 7.72
(d, J = 8.2 Hz, 2H, H-2ꢀ/H-6ꢀ); 13C NMR (75 MHz, DMSO-d6):
d 25.1 (CH3), 123.2 (C-2ꢀ/C-6ꢀ), 128.8 (C-4ꢀ), 129.8 (C-3ꢀ/ C-5ꢀ),
ꢀ
=
137.3 (C-1 ), 150.6 (C-5), 169.0 (C-2), 190.4 (Me–C O); HRMS
(EI): found 220.028431 (M+), C10H8N2O2S requires 220.030631;
m/z (EI): 220 (M+, 38%), 160 (20), 118 (73), 91 (100) and 77 (63).
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 9 9 – 2 6 0 3
2 6 0 1

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=
=
5-Acetyl-3-(4-methylphenyl)-1,3,4-thiadiazol-2(3H)-one 7b
156.2 (C-5), 188.9 (C(2) S), 189.1 (Me–C O); HRMS (EI):
found 250.021512 (M+), C11H10N2OS2 requires 250.023442; m/z
(EI): 250 (M+, 26%), 207 (2), 174 (3), 149 (86), 148 (30), 132 (32),
105 (65) and 91 (100).
This compound was prepared from 6b (2.8 g, 10 mmol) and
1,1ꢀ-carbonyldiimidazole (2.0 g, 12.5 mmol) by following the
same procedure described above for 7a. Yield 1.5 g (64%);
mp 87–88 ◦C (ethanol); found C, 56.28; H, 3.21; N, 11.75; S,
13.44%. C11H10N2O2S requires C, 56.40; H, 4.30; N, 11.96; S,
13.68%; mmax(KBr)/cm−1 3100, 3023, 2914, 2849, 1693 br, 1609,
1524, 1508, 1452, 1365, 1274, 1153, 1087 and 1059;1H- NMR
5-Acetyl-3-(4-chlorophenyl)-1,3,4-thiadiazol-2(3H)-thione 8c
This compound was prepared from 6c (3.0 g, 10 mmol) and
1,1ꢀ-thiocarbonyldiimidazole (2.2 g, 12.5 mmol) by following
the same procedure described above for 8a. Yield 1.84 g (68%);
(300 MHz, DMSO-d6): d 2.32 (s, 3H, Ar–CH3ꢀ), 2.52 (s, 3H,
◦
ꢀ
=
CH3–C O), 7.32 (d, J = 7.4 Hz, 2H, H-3 / H-5 ), 7.59 (d, J =
mp 122–123 C; found C, 44.12; H, 2.52; N, 10.13; S, 23.51%.
7.4 Hz, 2H, H-2ꢀ/H-6ꢀ);13C-NMR (75 MHz, DMSO-d6): d 21.2
(Ar–CH3), 25.1 (CH3–CO), 123.2 (C-2ꢀ/C-6ꢀ), 130.2 (C-3ꢀ/C-
C10H7ClN2OS2 requires C, 44.36; H, 2.61; N, 10.35; S, 23.68%;
mmax(KBr)/cm−1 3094, 3061, 2965, 2914, 2850, 1692, 1500,
1
5ꢀ), 134.2 (C-4ꢀ), 138.4 (C-1ꢀ), 150.3 (C-5), 169.0 (C-2), 190.4
1484, 1367, 1333, 1280, 1205, 1091, 1053 and 1015; H-NMR
+
=
(Me–C O); HRMS (EI): found 234.046179 (M ), C11H10N2O2S
(300 MHz, DMSO-d6): d 2.53 (s, 3H, CH3), 7.65 (d, J = 8.4 Hz,
2H, H-3ꢀ/H-5ꢀ), 7.75 (d, J = 8.4 Hz, 2H, H-2ꢀ/ H-6ꢀ); 13C-
NMR (75 MHz, DMSO-d6): d 26.0 (CH3), 128.8 (C-2ꢀ/C-6ꢀ),
129.9 (C-3ꢀ/C-5ꢀ), 134.8 (C-4ꢀ), 137.1 (C-1ꢀ), 156.5 (C-5), 189.0
requires 234.046281; m/z (EI): 234 (M+, 24%), 174 (16), 132 (64),
105 (100), 104 (23) and 91 (11).
=
=
5-Acetyl-3-(4-chlorophenyl)-1,3,4-thiadiazol-2(3H)-one 7c
(C(2) S), 189.1 (Me–C O); HRMS (EI): found 269.968284
(M+), C10H7ClN2OS2 requires 269.968816; m/z (EI): 270 (M+,
69%), 227 (1), 194 (10), 169 (100), 152 (71), 125 (65), 111 (42)
and 90 (12).
This compound was prepared from 6c (3.0 g, 10 mmol) and
1,1ꢀ-carbonyldiimidazole (2.0 g, 12.5 mmol) by following the
same procedure described above for 7a. Yield 1.6 g (63%); mp
102–103 ◦C (CHCl3–pet. ether); found C, 46.92; H, 2.58; N,
10.87; S, 12.44%. C10H7ClN2O2S requires C, 47.16; H, 2.77; N,
11.00; S, 12.59%; mmax(KBr)/cm−1 3094, 2914, 1692, 1525, 1486,
1371, 1268, 1146 and 1088;1H-NMR (300 MHz, DMSO-d6): d
2.45 (s, 3H, CH3), 7.58 (d, J = 8.0 Hz, 2H, H-3ꢀ/H-5ꢀ), 7.63
(d, J = 8.0 Hz, 2H, H-2ꢀ/H-6ꢀ); 13C-NMR (75 MHz, DMSO-
d6): d 25.0 (CH3), 124.6 (C-2ꢀ/C-6ꢀ), 129.4 (C-3ꢀ/C-5ꢀ), 132.8
Collection of X-ray diffraction data and structure analysis of 7b
Yellow block crystals were grown by allowing a clear solution of
7b in hot ethanol to evaporate slowly at rt such that its volume
was reduced by about 20% over 2–3 days. Crystal data collection
was made with a Siemens SMART CCD diffractometer [Mo–
Ka-radiation, graphite monochromator] operating in the omega
scan mode (0.3◦). The data were reduced with the Siemens-
Bruker program suite XSCANS13 and the structure was solved
by the direct method using SHELXTL PLUS programs.14 All
non-hydrogen atoms were refined anisotropically by full-matrix,
least-squares procedure based on F2 using all unique data.
ꢀ
ꢀ
=
(C-4 ), 136.1 (C-1 ), 150.8 (C-5), 169.0 (C-2), 190.4 (Me–C O);
HRMS (EI): found 253.990925 (M+), C10H7ClN2O2S requires
253.991655; m/z (EI): 254 (M+, 33%), 194 (29), 152 (88), 125
(100) and 90 (24).
5-Acetyl-3-phenyl-1,3,4-thiadiazol-2(3H)-thione 8a
Crystal structure determination of 7b
To a mixture of 1,1ꢀ-thiocarbonyldiimidazole (2.2 g, 12.5 mmol)
and compound 6a (2.7 g, 10 mmol) was added dry tetrahy-
drofuran (50 cm3) and the resulting solution was stirred at rt
for 4–5 h. The solvent was then removed in vacuo, the residue
was immediately treated with water (40 cm3) and extracted
with chloroform (2 × 40 cm3) The combined organic extracts
were dried (Na2SO4), the solvent was evaporated and the
residual solid product was purified by column chromatography
(silica gel), using dichloromethane as eluent, to afford the title
compound 8a as yellow solid. Yield 1.51 g (64%); mp 117–118 ◦C;
found 50.64; H, 3.28; N, 11.74; S, 27.02%. C10H8N2OS2 requires
C, 50.83; H, 3.41; N, 11.85; S, 27.13%; mmax(KBr)/cm−1 3055,
3004, 2959, 2920, 2849, 1686, 1503, 1498, 1360, 1332, 1288,
1203, 1060 and 1018;1H-NMR (300 MHz, DMSO-d6): d 2.52 (s,
3H, CH3), 7.57 (m, 3H, H-3ꢀ/H-5ꢀ, H-4ꢀ), 7.69 (dd, J = 8.2 Hz,
1.5 Hz, 2H, H-2ꢀ/H-6ꢀ); 13C-NMR (75 MHz, DMSO-d6): d 26.0
Crystal data. C11 H10 N2 O2 S, M = 234.27, monoclinic,
˚
a = 11.9376(16), b = 14.0036(19), c = 13.9101(19) A, b =
107.916(2)◦, Dcalcd = 1.407 g cm , U = 2212.6(5) A , T = 203(2)
K, space group P21/c, Z = 8, l(Mo–Ka) = 0.278 mm−1, 27 847
reflections measured (2hmax = 56.52◦), 5545 unique [Rint (F2) =
0.0279] which were used in all calculations. The final R1 was
−3
3
˚
0.0388 (Fo > 4r(F), 4467 data, 289 parameters), and wR2 (F2) =
−3
˚
0.1141 (all data), maximum residual electron density 0.39 e A .
Hydrogen atoms were placed in calculated positions and treated
as riding groups, with the 1.2 fold (1.5 fold for methyl groups)
isotropic displacement parameters of the equivalent Uij of the
corresponding carbon atom.
With two independent molecules, one has close O · · · S
ꢀ
˚
contacts via the inversion centres (O3–S21 2.925 A, C22–
O3–S21ꢀ 140.6◦), while the other does not exhibit significant
intermolecular contacts. The heterocycles adopt almost planar
conformations, the interplanar angles are 22.2 and 24.9◦,
respectively, for (S1, C2, N3, N4, C5)/(C8–C13) and (S21, C22,
N23, N24, C25)/(C28–C33). However, the torsion direction
is reversed as evident by the torsion angles N4–N3–C8–C9
−158.4◦ and N24–N23–C28–C29 156.1◦ as demonstrated by
the graphical overlay of both independent molecules (Fig. 2),
where the heterocycles are fitted best to each other.
(CH3), 126.9 (C-2ꢀ/C-6ꢀ), 129.8 (C-3ꢀ/C-5ꢀ), 130.4 (C-4ꢀ), 138.4
ꢀ
=
=
(C-1 ), 156.3 (C-5), 188.9 (C(2) S), 189.1 (Me–C O); HRMS
(EI): found 236.003228 (M+), C10H8N2OS2 requires 236.007792;
m/z (EI): 236 (M+, 64%), 235 (27), 193 (3), 160 (9), 135 (48), 118
(57), 91 (100) and 77 (64).
5-Acetyl-3-(4-methylphenyl)-1,3,4-thiadiazol-2(3H)-thione 8b
Crystallographic data for the structural analysis of 7b have
been deposited with the Cambridge Crystallographic Data
Center under the depository No. CCDC-260037. Copies of
information may be obtained free of charge from the Di-
rector, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: +44-1223-336033; e-mail: (deposit@ccdc.cam.ac.uk or
http://www.ccdc.cam.ac.uk).†
This compound was prepared from 6b (2.8 g, 10 mmol) and
1,1ꢀ-thiocarbonyldiimidazole (2.2 g, 12.5 mmol) by following
the same procedure described above for 8a. Yield 1.53 g (61%);
mp 76–77 ◦C; found C, 52.46; H, 3.88; N, 11.05; S, 25.36%.
C11H10N2OS2 requires C, 52.78; H, 4.03; N, 11.19; S, 25.61%;
mmax(KBr)/cm−1 3056, 3023, 2997, 2965, 2920, 2856, 1696, 1486,
1358, 1274, 1204, 1056 and 1017; 1H-NMR (300 MHz, DMSO-
d6): d 2.36 (s, 3H, CH3–Ar), 2.52 (s, 3H, CH3–CO), 7.36 (d, J =
8.2 Hz, 2H, H-3ꢀ/H-5ꢀ), 7.55 (d, J = 8.2 Hz, 2H, H-2ꢀ/H-6ꢀ); 13C-
NMR (75 MHz, DMSO-d6): d 21.3 (CH3–Ar), 26.0 (CH3CO),
126.6 (C-2ꢀ/C-6ꢀ), 130.2 (C-3ꢀ/C-5ꢀ), 136.0 (C-1ꢀ), 140.2 (C-4ꢀ),
† CCDC reference numbers 260037. See http://www.rsc.org/suppdata/
ob/b5/b505010c/ for crystallographic data in CIF or other electronic
format.
2 6 0 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 9 9 – 2 6 0 3

View Article Online
8 (a) M. A. A. Elneairy, A. A. Abbas and Y. N. Mabkhout, Phosphorus,
Sulfur Silicon Relat. Elem., 2003, 178, 1747–1757; (b) A. M. Farag,
H. M. Hassaneen, I. M. Abbas, A. S. Shawali and M. S. Algharib,
Phosphorus, Sulfur Silicon Relat. Elem., 1988, 40, 243–249; (c) A. O.
Abdelhamid and F. A. Attaby, Sulfur Lett., 1988, 7, 239–247;
(d) H. M. Hassaneen, A. O. Abdelhamid, A. S. Shawali and R.
Pagni, Heterocycles, 1982, 19, 319–326; (e) A. S. Shawali and A. O.
Abdelhamid, J. Heterocycl. Chem., 1976, 13, 45–49.
Acknowledgements
We thank the Deanship of Scientific Research-Jordan University
(Amman) for financial support.
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 9 9 – 2 6 0 3
2 6 0 3