Synthesis of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3- diphenylpropenones from alkenylidene-hydrazinecarbothioamides

Article abstract of DOI:10.1016/j.tet.2012.07.063

Conjugated alkenylidene-hydrazinecarbothioamides react in high yield with 2,3-diphenylcyclopropenone to give a series of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones.

Full text of DOI:10.1016/j.tet.2012.07.063

Tetrahedron 68 (2012) 8487e8492
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Tetrahedron
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Synthesis of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones
from alkenylidene-hydrazinecarbothioamides
,
a
a
a
b
Alaa A. Hassan a , Fathy F. Abdel-Latif , Ahmed M. Nour El-Din , Sara M. Mostafa , Martin Nieger ,
Stefan Brase
*
c
€
a Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt
b Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, 00014 Helsinki, Finland
c Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 April 2012
Received in revised form 21 June 2012
Accepted 17 July 2012
Conjugated alkenylidene-hydrazinecarbothioamides react in high yield with 2,3-diphenylcyclopropenone
to give a series of (E)-2,5-disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones.
Ó 2012 Elsevier Ltd. All rights reserved.
Available online 3 August 2012
Keywords:
Alkenylidene-hydrazinecarbothioamides
heterocyclizations
Thiadiazolyl-2,3-diphenylpropenone
derivatives
1. Introduction
N-Imidoylthioureas reacted with 1 to give pyrimidin-4(3H)-
ones.18 Substituted pyrrol-3-ones were formed during the reaction
Cyclopropenones undergo several interesting cycloaddition re-
actions that provide useful starting materials for a variety of com-
pounds.1e3 2,3-Diphenylcycloprop-2-enone (1) is stable, has
aromatic character and reacts with both electrophilic and nucleo-
philic reagents. Due to its strained ring, 2,3-diphenylcycloprop-2-
enone (1) acts as an ambident electrophile with the potential for
nucleophilic addition at the carbonyl group or conjugate
addition.4e7 These factors allow participation in a wide variety of
synthetically useful reactions and the use of diphenylcycloprope-
none in the preparation of a plethora of heterocyclic systems has
been systematically studied over the past few decades.8e16
Cycloaddition chemistry plays a major role in the synthetic ver-
satility of 2,3-diphenylcycloprop-2-enone (1). Compound 1 reacts
with a wide range of imine and other compounds containing the C]
N moiety to form azacyclopentenones (pyrrolinones) via a formal
[2þ3] cycloaddition reaction.9e16 The formal [2þ3] cycloaddition of
a twofold excess of 1 to azomethine imines generated from aryl-1,5-
diazabicyclo[3.1.0]hexanes afforded diazacyclopenta[cd]-inden-7-
ones.17
of N1, N2-diarylacetamidines, diimines and azines with 1, through
a formal [2þ3] cycloaddition reaction.19,20 Reaction of diphenylcy-
clopropenone with 2 equiv of substituted thiosemicarbazides re-
sults in the formation of 1,2,4-triazolo-[4,3-b]pyridazinethiones.21
N-Substituted hydrazine derivatives of thiosemicarbazides react
stoichiometrically to yield pyridazinethiones.21 In each case, the
reaction proceeds mechanistically via a formal [3þ3] cycloaddi-
tion.21 Recently, we reported that the reaction of various aldehyde
4-phenylthiosemicarbazones
2 with 2,3-diphenylcycloprop-2-
enone (1) in acetic acid effected the formation of pyrrolo[2,1-b]
[1,3,4]oxadiazoles 3 (Scheme 1).22
Scheme 1. Pyrrolo[2,1-b][1,3,4]oxadiazoles from diphenylcyclopropenone and
thiosemicarbazones.
On the other hand, the reaction of aldehyde and ketone thio-
semicarbazones with acid anhydrides or acid chlorides gave 1,3,4-
thiadiazoline derivatives.23,24
* Corresponding author. Tel./fax: þ20 862363011; e-mail address: alaa-
hassan2001@yahoo.com (A.A. Hassan).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.063

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A.A. Hassan et al. / Tetrahedron 68 (2012) 8487e8492
This fascinating versatility in the reaction of aldehyde 4-
phenylthiosemicarbazones 2 with 1 justifies further investigation
of the reactivity of diphenylcyclopropenone towards
alkenylidene-hydrazinecarbothioamides 2aep (Scheme 2).
the presence of one doublet at dH¼(1.70 ppm, J¼6.7 Hz), due to
methyl group and two multiplets at 5.64 and 5.83e5.85 ppm due to
(AreCH]CH), a broad band at 7.44 ppm due to NH, in addition to
the aromatic protons. The 13C NMR spectrum of 4k showing two
downfield lines at 166.5 and 152.5 ppm due to (CO) and
thiadiazoleeC]N, respectively. The 13C NMR spectrum supported
the 1H NMR spectroscopic data by distinctive appearance of carbon
signals representing AreCH]CH at 118.2 and 122.6 ppm, whereas
the thiadiazoleeCH group resonated at 67.52 ppm.
1
The molecular formulae of 4aep are supported by the mass
spectra, which gave the predicted molecular ion peaks. It should
also be noted that the mass spectra of compounds 4aep are char-
acterized by four fragments common to all products [MþꢀRN]C]
S], 207 (PheCH]CPh)COþ, 178 (PheChCePh) and RN]C]S.
Moreover, the structure of 4k has been unambiguously con-
firmed by a single crystal X-ray structure analysis (Fig. 1, and Tables
1e5 in the Supplementary data), which confirms a cisoid geometry
with respect to the central C42eC43 double bond (note that the
crystallographic numbering does not correspond to the systematic
ꢀ
IUPAC numbering rules), showing a bond length of 1.338 (3) A and
thus being slightly longer than an unperturbed C]C double bond,
with a dihedral angle C(421)eC(42)eC(43)eC(431) of ꢀ7.7(3)ꢁ. The
sum of C(41)eN(4)eN(3), C(41)eN(4)eC(5) and N(3)eN(4)eC(5)
angles is close to 360ꢁ as are the sums of the angles around C(41),
C(42) and C(43) demonstrating planarity around N(4), C(41), C(42)
and C(43), whereas the sum of angles N(4)eC(5)eC(51), N(4)e
C(5)eS1 and C(51)eC(5)eS1 is 327.11ꢁ, revealing a pyramidalization
at C5. On the other hand, each angle of N(4)eC(5)eH(5), C(51)e
C(5)eH(5) and S1eC(5)eH(5) is equal to 109.8ꢁ. Also, from the data
of the X-ray crystal structure the C(2)eN(3)eN(4) angle is 109.37ꢁ
and therefore close to those of sp3 nitrogen. One may conclude that
the lone pair on this nitrogen is not contributing much to the actual
state of the molecule; although, the thiadiazole ring is almost
planar.
Scheme 2. Reaction of 2,3-diphenylcycloprop-2-enone (1) and alkenylidene-
hydrazinecarbothioamides 2.
2. Results and discussion
Compounds 2aep may react at least with their sulfur atom, N2
and N4 as well as azomethine-nitrogen as nucleophilic sites. Thus,
several options for interactions between 1 and 2 may be envisaged,
as will be outlined later.
In this paper we describe the synthesis of (E)-2,5-disubstituted-
1,3,4-thiadiazolyl-2,3-diphenylpropenones 4aep from the reaction
of 2,3-diphenylcycloprop-2-enone (1) and alkenylidene-
hydrazinecarbothioamides 2aep by refluxing equimolar amounts
of the reactants in ethanol as solvent. Compounds 4aep were
obtained as crystalline solids in 69e84% yield (Scheme 2).
Elemental analyses and mass spectra of these molecules clearly
revealed that the products were formed by the addition of one
molecule of 1 to one molecule of 2aep without any elimination.
The IR spectra of the isolated compounds from the reaction of 1
with 2aep showed absorptions of the NH group at
3315e3280 cmꢀ1 and two strong bands at 1690e1670,
1630e1615 cmꢀ1 due to the carbonyl group and C]N vibration,
respectively. The IR spectra did not reveal absorption due to C]S or
OH groups. The 1H NMR spectra of compounds 4aep show the
absence of any signals due to HeN2 or azomethine (CH]Ne)
groups but show the NH proton signals at dH¼7.30e7.67 (NHePh),
6.65e6.90 (NHeCH2Ph) and 6.15e6.65 (NH-allyl), the signal of
thiadiazoleeCH proton at 6.15e6.58, as well as the substituents
(R0), in addition to the aromatic protons.
Fig. 1. Molecular structure of 4k in the crystal (displacement parameters are drawn at
50% probability level). The crystallographic numbering does not reflect the systematic
IUPAC numbering.
From these data it can be concluded that the S]CeNHeN]
CHR0 group was changed, thus both the thioxo sulfur and azome-
thine groups had taken part in the heterocyclization. Since the
electrophilic cyclopropenone could be attacked by the following
nucleophilic sites, sulfur atom, N2 and N1 or the azomethine carbon
In the 13C NMR spectra of 4aep signals at dC¼66.1e68.5 ppm
were assigned to (thiadiazoleeCH), 147.0e156.3 due to
(thiadiazoleeC]N) and 164.7e168.2 ppm (CO). The following ad-
ditional remarks are necessary: the 1H NMR spectrum of 4k shows

A.A. Hassan et al. / Tetrahedron 68 (2012) 8487e8492
8489
of 2aep, which had to act as a nucleophile in the sense of an
‘umpolung’.25 This behaviour is not unexpected since aldehyde
hydrazones are known to react as azaenamines26e28 towards suit-
able electrophiles. This behaviour should consequently also be
open to aldehyde thiosemicarbazones, since the substituted thio-
carbamoyl group is not a strong acceptor and may even be sterically
hindered. The formation of 4aep may be rationalized as an initial
attack of azomethine (CH]N) nitrogen atom of the alkenylidene-
hydrazinecarbothioamides 2aep to the carbonyl group of cyclo-
propenone 1. A spontaneous intramolecular nucleophilic addition
from the lone pair of the sulfur atom on the CH]N group followed
by cyclization to yield the intermediate 5, which rearranges to the
final structures, the 2,5-disubstituted 1,3,4-thiadiazolyl-2,3-
diphenylpropenones 4aep. The structure of the obtained prod-
ucts excluded formal [2þ3] cycloaddition pathways, such as pro-
posed by Eicher.9e12 (Scheme 3).
solvents listed. Zones were detected by quenching of indicator
fluorescence upon exposure to 254 nm light and eluted with ace-
tone. The solvents used were purified and dried according to
standard procedures.29
4.2. Starting materials
Substituted alkenylidene-hydrazinecarbothioamides 2aep
were prepared by the reaction of 4-substituted thiosemicarbazide
with the proper aldehyde according to published procedures in
literature: (2a),30 (2b),31 (2c),32 (2d),33 (2e),31 (2f),31 (2g),34 (2h),33
(2i),31 (2j),31 (2k),35 (2l),31 (2m),31 (2n),33 (2o),36 (2p).31
4.3. Products
A mixture of substituted (ylidene)hydrazinecarbothioamide
2aep (1.00 mmol) in absolute ethanol (25 mL) and a solution of 1
(0.206 g, 1.00 mmol) in absolute ethanol (20 mL) were mixed
dropwise with stirring. The mixture was refluxed with stirring for
4e6 h (the reaction was monitored by TLC analyses). The solvent
was concentrated and the residue was subjected to preparative
layer chromatography (plc) using toluene/ethyl acetate (2:1) as the
developing solvent to give one main zone. The zones were
extracted and recrystallized from the appropriate solvent and
identified as follows:
4.3.1. (2E)-2,3-Diphenyl-1-[5-(phenylamino)-2-styryl-1,3,4-
thiadiazol-3(2H)-yl]prop-2-en-1-one
(4a). Colourless
crystals
(0.398 g, 82%), mp 158e160 ꢁC (acetonitrile). IR (KBr)
n¼3290 (NH),
3060 (AreCH), 1680 (CO), 1625 (C]N), 1600 (AreC]C) cmꢀ1 1H
;
NMR (CDCl3): dH¼7.67 (br, 1H, NH), 6.90e7.41 (m, 12H, AreH),
6.79e6.81 (m, 6H, AreH), 6.71e6.73 (m, 4H, AreH), 6.39 (m, 1H,
AreH), 6.31e6.34 (m, 1H, thiadiazoleeCH); 13C NMR (CDCl3):
dC¼166.7 (CO), 147.0 (thiadiazole C-5), 138.3, 136.1, 135.0, 134.9,
134.5 (Ar C), 132.6, 131.1, 128.7, 128.3, 127.9, 127.8, 127.7, 127.6, 127.5,
127.4, 127.3, 126.8, 126.0, 125.7, 125.1 (Ar CH), 66.8 (thiadiazo-
leeCH); MS: m/z 487 (Mþ, 11), 352 (17), 207 (19), 179 (36), 135
(100), 77 (56), 65 (46). Anal. Calcd for C31H25N3OS (487.61): C,
76.36; H, 5.17; N, 8.62; S, 6.58. Found: C, 76.45; H, 5.23; N, 8.49; S,
6.77.
Scheme 3. Mechanism rationale for the formation of (E)-2,5-disubstituted-1,3,4-
thiadiazolyl-2,3-diphenylpropenones 4.
3. Conclusion
The present investigation clearly indicates that the products
obtained from the conjugate addition of alkenylidene-
hydrazinecarbothioamides 2aep to 2,3-diphenylcycloprop-2-
enone (1), followed by heterocyclization, are neither the result of
[2þ3] or [3þ3] cycloadditions as reported earlier. Novel (E)-2,5-
disubstituted 1,3,4-thiadiazolyl-2,3-diphenylpropenones are ob-
served due to the azaenamine reactivity shown by the starting
materials 2aep. This reactivity requires the availability of the
azomethine carbon, N2, N4 and sulfur atom as nucleophilic sites.
4.3.2. (2E)-1-[5-(Benzylamino)-2-styryl-1,3,4-thiadiazol-3(2H)-yl]-
3,3-diphenylprop-2-en-1-one (4b). Colourless crystals (0.374 g,
75%), mp 166e168 ꢁC (ethanol). IR (KBr)
n
¼3295 (NH), 1680 (CO),
1630 (C]N), 1600 (AreC]C) cmꢀ1; 1H NMR (CDCl3): dH¼7.38e7.00
(m, 11H, AreH), 6.94e6.92 (m, 6H, AreH), 6.70 (br, 1H, NH),
6.58e6.55 (m, 4H, AreH), 6.36e6.34 (m, 2H, AreH), 6.20e6.18 (m,
1H, thiadiazoleeCH), 4.2 (s, 2H, CH2). 13C NMR (CDCl3): dC¼165.7
(CO), 152.5 (thiadiazoleeC-5), 138.1, 136.9, 136.6, 136.2, 135.2
(AreC), 132.1, 131.2, 128.8, 128.4, 127.6, 127.5, 127.4, 127.3, 127.0,
126.8, 126.7, 126.3, 126.0, 125.1, 124.5 (AreCH), 66.9 (thiadiazo-
leeCH), 48.9 (CH2); MS: m/z 501 (Mþ, 16), 352 (21), 313 (32), 207
(22), 179 (39), 177 (58), 149 (36), 91 (100), 65 (18). Anal. Calcd for
C32H27N3OS (501.64): C, 76.62; H, 5.43; N, 8.38; S, 6.39. Found: C,
76.78; H, 5.33; N, 8.30; S, 6.56.
4. Experimental
4.1. Chemistry
All melting points were determined using open capillaries on
a Gallenkamp melting point apparatus. The IR spectra were recor-
ded with a Shimadzu 408 instrument using potassium bromide.
The 400 MHz 1H NMR and 100 MHz 13C NMR spectra were ob-
served on a Bruker AM 400 spectrometer with tetramethylsilane as
the internal standard, br¼broad, s¼singlet, d¼doublet, t¼triplet,
q¼quartet, m¼multiplet. The 13C NMR signals were assigned on the
basis of DEPT 135/90 spectra. The mass spectra (70 eV, electron
impact mode) were recorded on Finnigan MAT instrument.
Elemental analyses carried out at the Microanalytical Center,
Cairo University, Egypt. Preparative layer chromatography (plc)
used air-dried 1.0 mm thick layers of slurry applied silica gel (Merck
Pf254) on 48 cm wide and 20 cm high glass plates using the
4.3.3. (2E)-1-[5-(Allylamino)-2-styryl-1,3,4-thiadiazol-3(2H)-yl]-
2,3-diphenylprop-2-en-1-one (4c). Colourless crystals (0.314 g,
70%), mp 142e143 ꢁC (ethanol). IR (KBr)
n
¼3280 (NH), 1675 (CO),
1625 (C]N), 1585 (AreC]C) cmꢀ1; 1H NMR (CDCl3): dH¼7.40e6.93
(m, 8H, AreH), 6.88e6.85 (m, 4H, AreH), 6.67e6.65 (m, 5H, AreH),
6.30 (br, 1H, NH), 6.23e6.20 (m, 1H, AreH), 6.17e6.15 (m, 1H,
thiadiazoleeCH), 5.76e5.73 (m, 1H, allyleCH]), 5.05e5.03 (m, 2H,
allyleCH2]), 4.07e4.05 (m, 2H, allyleCH2N). 13C NMR (CDCl3):
dC¼166.8 (CO), 152.3 (thiadiazole C-5), 134.6 (allyleCH]), 136.6,
132.7, 132.6, 132.4 (AreC), 131.2, 130.6, 129.7, 128.8, 128.7, 127.6,

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A.A. Hassan et al. / Tetrahedron 68 (2012) 8487e8492
127.3, 127.2, 126.8, 126.3, 126.0, 125.1 (AreCH), 116.1 (allyleCH2]),
66.7 (thiadiazoleeCH), 46.4 (allyleCH2N). MS (EI): m/z¼451 (Mþ,
11), 352 (8), 244 (42), 207 (26), 179 (59), 177 (100), 99 (24), 77 (26),
41 (47). Anal. Calcd for C28H25N3OS (451.58): C, 74.47; H, 5.58; N,
9.31; S, 7.10. Found: C, 74.58; H, 5.49; N, 9.18; S, 6.96.
(thiadiazoleeCH), 13.0 (CH3); MS (EI): m/z¼501 (Mþ, 11), 366 (16),
222 (31), 207 (36), 179 (100), 177 (21), 135 (52), 91 (18), 77 (28).
Anal. Calcd for C32H27N3OS (501.64): C, 76.62; H, 5.43; N, 8.38; S,
6.39. Found: C, 76.53; H, 5.51; N, 8.28; S, 6.57.
4.3.8. (2E)-1-[[2-(Pent-1-enyl)-5-(phenylamino)-1,3,4-thiadiazol-
4.3.4. (2E)-1-[2-(2-Methoxystyryl)-5-(phenylamino)-1,3,4-
thiadiazol-3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4d). Colourless
crystals (0.371 g, 72%), mp 172e174 ꢁC (acetonitrile). IR (KBr)
3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4h). Colourless crystals
(0.374 g, 83%), mp 143e144 ꢁC (ethanol). IR (KBr)
n
¼3310 (NH),
3070 (AreCH), 2980 (AlieCH), 1675 (CO), 1620 (C]N), 1590
(AreC]C) cmꢀ1; 1H NMR (CDCl3): dH¼7.38e7.35 (m, 4H, AreH and
NH), 7.32e7.25 (m, 5H, AreH), 7.22e7.09 (m, 6H, AreH), 6.87e6.85
(m, 2H, AreH), 6.56e6.55 (m, 1H, thiadiazoleeCH), 5.67e5.65,
5.42e5.40 (m, 2H, CH]CH), 1.97e1.95 (m, 2H, CH2), 1.32e1.30 (m,
2H, CH2), 0.85 (t, J¼7.6 Hz, 3H, CH3); 13C NMR (CDCl3): dC¼166.5
(CO), 149.0 (thiadiazole C-5), 136.3, 135.0, 134.7, 133.2 (AreC), 132.2,
128.7, 128.3, 127.9, 127.6, 127.4, 127.0, 126.7, 126.6, 125.0 (AreCH),
121.6, 117.4 (CH]CH), 67.6 (thiadiazoleeCH), 33.7 (CH2), 21.8 (CH2),
13.6 (CH3); MS (EI): m/z¼453 (Mþ, 15), 384 (38), 356 (53), 318 (54),
22 (19), 207 (36), 179 (100), 177 (62), 135 (22), 91 (16), 77 (18). Anal.
Calcd for C28H27N3OS (453.60): C, 74.14; H, 6.00; N, 9.26; S, 7.07.
Found: C, 74.22; H, 6.07; N, 9.45; S, 6.93.
n
¼3310 (NH), 3050 (AreCH), 1680 (CO), 1620 (C]N), 1600 (AreC]
C) cmꢀ1; 1H NMR (CDCl3): dH¼7.58 (br, 1H, NH), 7.40e7.07 (m, 10H,
AreH), 6.94e6.89 (m, 3H, AreH), 6.87e6.85 (m, 3H, AreH),
6.83e6.82 (m, 5H, AreH), 6.40e6.38 (m, 1H, AreH), 6.34e6.32 (m,
1H, thiadiazoleeCH), 3.79 (s, 3H, OCH3), 13C NMR (CDCl3): dC¼166.6
(CO), 156.3 (AreCeO), 156.2 (thiadiazole C-5), 136.6, 136.4, 136.2,
135.0, 134.7 (AreC), 132.7, 129.7, 128.7, 128.3, 127.9, 127.8, 127.6,
127.4, 127.2, 127.0, 126.9, 126.7, 126.6, 126.3, 125.1 (AreCH), 67.0
(thiadiazoleeCH), 54.4 (OCH3); MS (EI): m/z¼517 (Mþ, 8), 382 (26),
207 (21), 179 (177), 177 (100), 135 (24), 91 (17), 77 (26). Anal. Calcd
for C32H27N3O2S (517.64): C, 74.25; H, 5.26; N, 8.12; S, 6.19. Found: C,
74.36; H, 5.37; N, 7.97; S, 6.35.
4.3.5. (2E)-1-[5-(Benzylamino)-2-(2-methoxy-styryl)-1,3,4-
thiadiazol-3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4e). Colourless
crystals (0.402 g, 76%), mp 177e179 ꢁC (acetonitrile). IR (KBr)
4.3.9. (2E)-1-[5-(Benzylamino)-2-(pent-1-enyl)-1,3,4-thiadiazol-
3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4i). Colourless crystals
(0.302 g, 65%), mp 147e148 ꢁC (ethanol). IR (KBr)
3040 (AreCH), 2970 (AlieCH), 1675 (CO), 1625 (C]N), 1600
n
¼3285 (NH),
n
¼3280 (NH), 1675 (CO), 1615 (C]N), 1585 (AreC]C) cmꢀ1
;
1H
NMR (CDCl3): dH¼7.50e6.94 (m, 10H, AreH), 6.91e6.89 (m, 3H,
AreH), 6.85e6.83 (m, 4H, AreH), 6.77e6.76 (m, 4H, AreH), 6.68 (br,
1H, NH), 6.42e6.40 (m, 1H, AreH), 6.37e6.36 (m, 1H, thiadiazo-
leeCH), 3.95 (s, 2H, CH2), 3.80 (s, 3H, OCH3). 13C NMR (CDCl3):
dC¼165.7 (CO),156.3 (AreCeO),152.7 (thiadiazole C-5),136.8, 136.7,
136.6, 136.2, 135.2 (AreC), 132.6, 128.8, 128.3, 127.8, 127.6, 127.5,
127.4, 127.2, 127.0, 126.9, 126.7, 126.6, 126.5, 126.4, 125.8 (AreCH),
67.6 (thiadiazoleeCH), 54.4 (OCH3), 47.8 (CH2). MS (EI): m/z¼531
(Mþ, 9), 382 (11), 207 (16), 179 (46), 177 (36), 149 (38), 91 (100), 77
(22). Anal. Calcd for C33H29N3O2S (531.67): C, 74.55; H, 5.50; N, 7.90;
S, 6.03. Found: C, 74.73; H, 5.39; N, 8.12; S, 5.89.
(AreC]C) cmꢀ1
;
1H NMR (CDCl3): dH¼7.39e7.35 (m, 5H, AreH),
7.33e7.27 (m, 5H, AreH), 7.25e7.05 (m, 4H, AreH), 6.90e6.88 (m,
2H, AreH), 6.85 (br, 1H, NH), 6.33e6.32 (m, 1H, thiadiazoleeCH),
5.85e5.83, 5.64e5.62 (m, 2H, CH]CH), 4.10 (s, 2H, CH2), 2.05e2.07
(m, 2H, CH2), 1.38e1.39 (m, 2H, CH2), 0.84 (t, J¼7.7 Hz, 3H, CH3); 13
C
NMR (CDCl3): dC¼164.7 (CO), 149.1 (thiadiazole C-5), 136.3, 135.8,
135.1, 135.0 (AreC), 133.8, 129.6, 128.9, 127.9, 127.6, 127.0, 126.9,
126.4, 126.0, 125.8 (AreCH), 123.1, 118.3 (CH]CH), 67.8 (thiadia-
zoleeCH), 46.8 (CH2ePh), 33.8 (CH2), 20.8 (CH2), 12.6 (CH3); MS: m/
z 467 (Mþ, 12), 318 (41), 222 (28), 207 (38), 179 (100), 177 (46), 91
(12). Anal. Calcd for C29H29N3OS (467.63): C, 74.48; H, 6.25; N, 8.99;
S, 6.86. Found: C, 74.66; H, 6.31; N, 8.87; S, 7.05.
4.3.6. (2E)-1-[5-(Allylamino)-2-(2-methoxy-styryl)-1,3,4-thiadiazol-
3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4f). Colourless crystals
4.3.10. (2E)-1-[5-(Allylamino)-2-(pent-1-enyl)-1,3,4-thiadiazol-
(0.326 g, 68%), mp 150e151 ꢁC (ethanol). IR (KBr)
n
¼3305 (NH),
3(2H)-yl]-2,3-diphenylprop-2-en-1-one (4j). Colourless crystals
3080 (AreCH), 1675 (CO), 1615 (C]N), 1580 (AreC]C) cmꢀ1 1H
;
(0.295 g, 71%), mp 126e127 ꢁC (ethanol). IR (KBr)
n
¼3305 (NH),
NMR (CDCl3): dH¼7.39e7.35 (m, 4H, AreH), 7.33e7.27 (m, 7H,
AreH), 7.22e7.05 (m, 3H, AreH), 6.90e6.88 (m, 2H, AreH), 6.28 (br,
1H, NH), 6.26e6.25 (m, 1H, thiadiazoleeCH), 6.22e6.20 (m, 1H,
AreH), 5.69e5.68 (m, 1H, allyleCH]), 5.02e5.00 (m, 2H,
3060 (AreCH), 2980 (AlieCH), 1690 (CO), 1630 (C]N), 1595
(AreC]C) cmꢀ1
;
1H NMR (CDCl3): dH¼7.37e7.30 (m, 4H, AreH),
7.25e7.18 (m, 5H, AreH), 7.15e7.00 (m, 2H, AreH), 6.36e6.35 (m,
1H, thiadiazoleeCH), 6.25 (br, 1H, NH), 6.03e6.00, 5.96e5.95,
6.00e6.03 (m, 2H, CH]CH), 5.86e5.85 (m, 1H, allyleCH]),
5.13e5.10 (m, 2H, allyleCH2]), 3.96e3.95 (m, 2H, allyleCH2N),
2.07e2.05 (m, 2H, CH2), 1.44e1.42 (m, 2H, CH2), 0.87 (t, J¼7.6 Hz,
3H, CH3); 13C NMR (CDCl3): dC¼164.7 (CO), 149.1 (thiadiazole C-5),
135.9 (allyleCH]), 135.1, 134.9 (AreC), 122.1, 118.4 (CH]CH), 129.6,
128.9, 128.3, 127.9, 127.4, 127.0, 126.1, 125.8 (AreCH), 115.9
(allyleCH2]), 66.7 (thiadiazoleeCH), 45.5 (allyleCH2N), 33.8 (CH2),
20.8 (CH2), 12.6 (CH3); MS (EI): m/z¼417 (Mþ, 8), 222 (22), 207 (28),
179 (100), 177 (42), 77 (23). Anal. Calcd for C25H27N3OS (417.57): C,
71.91; H, 6.52; N, 10.06; S, 7.68. Found: C, 72.08; H, 6.44; N, 9.93; S,
7.87.
allyleCH2]), 4.13e4.10 (m, 2H, allyleCH2N), 3.80 (s, 3H, OCH3). 13
C
NMR (CDCl3): dC¼166.7 (CO), 157.3 (AreCeO), 153.9 (thiadiazole C-
5), 135.7 (allyl-CH]), 137.6, 137.2, 136.6, 136.3, 133.6 (AreC), 133.5,
130.7, 129.8, 129.5, 129.4, 128.6, 128.3, 127.9, 127.4, 126.8, 126.2,
125.4 (AreCH), 117.1 (allyleCH2]), 68.5 (thiadiazoleeCH), 55.5
(OCH3), 47.4 (allyleCH2N). MS (EI): m/z¼481 (Mþ, 8), 382 (11), 263
(38), 207 (24), 179 (100), 177 (71), 133 (21), 99 (48), 41 (42). Anal.
Calcd for C29H27N3O2S (481.61): C, 72.32; H, 5.65; N, 8.72; S, 6.66.
Found: C, 72.46; H, 5.53; N, 8.59; S, 6.81.
4.3.7. (2E)-2,3-Diphenyl-1-[5-(phenylamino)-2-(1-phenylprop-1-en-
2-yl)-1,3,4-thiadiazol-3(2H)-yl]prop-2-ene-1-one (4g). Colourless
crystals (0.419 g, 84%), mp 166e168 ꢁC (ethanol). IR (KBr)
n
¼3310
4.3.11. (2E)-2,3-Diphenyl-1-[5-(phenylamino)-2-(prop-1-enyl)-1,3,4-
(NH), 3050 (AreCH), 1675 (CO), 1620 (C]N), 1590 (AreC]C) cmꢀ1
;
thiadiazol-3(2H)-yl]prop-2-en-1-one
(4k). Colourless
crystals
1H NMR (CDCl3): dH¼7.30e7.20 (m, 6H, AreH and NH), 7.18e7.05
(m, 10H, AreH), 7.00e6.85 (m, 6H, AreH), 6.67e6.65 (m, 1H, AreH),
6.43e6.42 (m, 1H, thiadiazoleeCH), 1.85 (s, 3H, CH3); 13C NMR
(CDCl3): dC¼168.2 (CO), 148.0 (thiadiazole C-5), 137.5, 137.1, 136.5,
136.1, 135.6, 133.5 (AreC), 133.1, 129.7, 129.4, 129.3, 129.1, 128.9,
128.8, 128.6, 128.4, 128.1, 127.8, 127.5, 126.6, 126.4 (AreCH), 67.6
(0.317 g, 75%), mp 132e133 ꢁC (ethanol). IR (KBr)
n
¼3290 (NH), 3050
(AreCH), 1675 (CO), 1630 (C]N), 1595 (AreC]C) cmꢀ1 1H NMR
;
(CDCl3): dH¼7.44 (br, 1H, NH), 7.40e7.38 (m, 3H, AreH), 7.36e7.25
(m, 8H, AreH), 7.23e7.08 (m, 3H, AreH), 6.97e6.91 (m, 2H, AreH),
6.65e6.63 (m, 1H, thiadiazoleeCH), 5.85e5.83, 5.64 (m, 2H, CH]
CH), 1.70 (d, J¼6.6 Hz, 3H, CH3); 13C NMR (CDCl3): dC¼166.5 (CO),

A.A. Hassan et al. / Tetrahedron 68 (2012) 8487e8492
8491
152.5 (thiadiazole C-5), 138.4, 136.2, 144.0, 134.7 (Ar C), 132.7, 128.7,
128.3,128.1,127.9,127.8,127.6,127.4,127.0,126.2 (Ar CH),122.6,118.2
(CH]CH), 67.5 (thiadiazole CH), 17.3 (CH3); MS (EI): m/z¼425 (Mþ,
12), 290 (26), 222 (14), 207 (36), 179 (100), 177 (61), 150 (13), 135
(18), 77 (21). Anal. Calcd for C26H23N3OS (425.55): C, 73.38; H, 5.45;
N, 9.87; S, 7.54. Found: C, 73.56; H, 5.57; N, 9.73; S, 7.71.
z¼441 (Mþ, 24), 387 (26), 292 (18), 207 (78), 179 (100), 177 (68), 91
(97), 77 (14). Anal. Calcd for C27H27N3OS (441.59): C, 73.44; H, 6.16;
N, 9.52; S, 7.26. Found: C, 73.61; H, 6.27; N, 9.42; S, 7.45.
4.3.16. (E)-1-[5-(Allylamino)-2-isopropyl-1,3,4-thiadiazol-3(2H)-yl]-
2,3-diphenyl-2-en-1-one (4p). Colourless crystals (0.268 g, 69%),
mp 112e113 ꢁC (benzene). IR (KBr)
n
¼3315 (NH), 3090 (AreCH),
4.3.12. (2E)-1-[5-(Benzylamino)-2-(prop-1-enyl)-1,3,4-thiadiazol-
2975 (AlieCH), 1680 (CO), 1630 (C]N), 1605 (AreC]C) cmꢀ1 1H
;
3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4l). Colourless crystals
NMR (CDCl3): dH¼7.38e7.22 (m, 5H, AreH), 7.20e6.95 (m, 6H,
AreCH), 6.29e6.28 (m, 1H, thiadiazoleeCH), 6.15 (br, 1H, NH),
5.67e5.65 (m, 1H, allyleCH]), 5.0 (m, 2H, allyl-CH2]), 4.12e4.10
(m, 2H, allyleCH2N), 2.39e2.38 (m, 1H, CH), 0.85 (d, J¼6.6 Hz, 6H,
2CH3); 13C NMR (CDCl3): dC¼167.9 (CO), 153.0 (thiadiazole C-5),
138.3, 136.9, 133.8 (Ar C), 135.8 (allyleCH]), 132.8, 129.8, 129.3,
128.7, 128.2, 128.1, 127.9, 127.6 (AreCH), 116.9 (allyl-CH2]), 47.1
(allyleCH2N), 66.1 (thiadiazoleeCH), 33.0 (CH), 18.4 (CH3); MS (EI):
m/z¼391 (Mþ, 57), 349 (18), 292 (14), 207 (64), 179 (100), 177 (84),
99 (17), 41 (15). Anal. Calcd for C23H25N3OS (391.53): C, 70.56; H,
6.44; N, 10.73; S, 8.19. Found: C, 70.39; H, 6.38; N, 10.62; S, 8.36.
(0.310 g, 71%), mp 139e140 ꢁC (acetonitrile). IR (KBr)
n
¼3310 (NH),
3070 (AreCH), 1680 (CO), 1630 (C]N), 1600 (AreC]C) cmꢀ1 1H
;
NMR (CDCl3): dH¼7.30e7.25 (m, 5H, AreH), 7.22e7.15 (m, 6H,
AreH), 7.12e7.00 (m, 5H, AreH), 6.90 (br, 1H, NH), 6.51e6.50 (m,
1H, thiadiazoleeCH), 5.84e5.82, 5.56e5.55 (m, 2H, CH]CH), 4.10
(s, 2H, CH2Ph), 1.65 (d, J¼6.6 Hz, 3H, CH3); 13C NMR (CDCl3):
dC¼165.9 (CO), 151.5 (thiadiazole C-5), 136.7, 136.6, 135.8, 134.7
(AreC), 132.6, 129.7, 128.8, 128.3, 126.6, 127.6, 127.4, 127.2, 126.9,
126.2 (AreCH), 121.8, 118.2 (CH]CH), 67.8 (thiadiazoleeCH), 47.8
(CH2),16.4 (CH3); MS (EI): m/z¼439 (Mþ,19), 370 (10), 290 (29), 207
(35), 179 (100), 177 (58), 149 (14), 91 (64). Anal. Calcd for
C27H25N3OS (439.57): C, 73.77; H, 5.73; N, 9.56; S, 7.29. Found: C,
73.96; H, 5.61; N, 9.72; S, 7.22.
4.4. Single crystal X-ray structure determination of 4k
Suitable crystals were obtained by recrystallization from abso-
lute ethanol. The single crystal X-ray diffraction study were carried
out on a Bruker-Nonius ApexII diffractometer at 123(2) K using
4.3.13. (2E)-1-[5-(Allylamino)-2-(prop-1-enyl)-1,3,4-thiadiaz-ol-
3(2H)-yl]-2,3-diphenyl-prop-2-en-1-one (4m). Colourless crystals
(0.259 g, 67%), mp 110e111 ꢁC (ethanol). IR (KBr)
n
¼3280 (NH),
MoK
a
radiation (
l
¼0.71073 A). Direct Methods (SHELXS-9735) were
ꢀ
3060 (AreCH), 1680 (CO), 1620 (C]N), 1600 (AreC]C) cmꢀ1 1H
;
used for structure solution and refinement was carried out using
SHELXL-9737 (full-matrix least-squares on F2). Hydrogen atoms
were localized by difference electron density determination and
refined using a riding model.
NMR (CDCl3): dH¼7.42e7.26 (m, 5H, AreH), 7.22e7.15 (m, 4H,
AreH), 7.12e6.90 (m, 2H, AreH), 6.30 (br, 1H, NH), 6.27e6.25 (m,
1H, thiadiazoleeCH), 5.92e5.90 (m, 1H, allyleCH]), 5.81e5.80,
5.52e5.50 (m, 2H, CH]CH), 5.06e5.05 (m, 2H, allyleCH2]),
4.13e4.10 (m, 2H, allyleCH2N), 1.70 (d, J¼6.7 Hz, 3H, CH3); 13C NMR
(CDCl3): dC¼164.7 (CO), 149.0 (thiadiazole C-5), 135.9 (allyleCH]),
136.1, 135.2, 134.9 (AreC), 132.8, 129.6, 128.9, 127.8, 127.4, 126.9,
125.4 (Ar CH), 122.1, 118.8 (CH]CH), 116.1 (allyleCH2]), 67.9
(thiadiazole CH), 45.2 (allyleCH2N), 17.6 (CH3); MS (EI): m/z¼389
(Mþ, 9), 290 (26), 222 (19), 207 (33), 179 (100), 177 (56), 77 (12), 41
(18). Anal. Calcd for C23H23N3OS (389.51): C, 70.92; H, 5.95; N,
10.79; S, 8.23. Found: C, 71.11; H, 5.87; N, 10.94; S, 8.35.
Compound 4k: C26H23N3OS, Mr¼425.53 g molꢀ1, colourless
crystals, crystal size 0.35ꢂ0.25ꢂ0.10 mm, monoclinic, space group
ꢀ
ꢀ
ꢀ
P2(1)/c (No. 14), a¼8.5272(2) A, b¼16.6230(6) A, c¼15.4999(6) A,
3
ꢀ
b
¼91.254(2)ꢁ, V¼2196.55(13) A , Z¼4, Dcalcd¼1.287 Mgmꢀ3
,
m
¼0.171 mmꢀ1
T¼123(2) K, 17,105 reflections, 4983 unique
,
[Rint¼0.031], 2qmax¼55ꢁ, R1 [for I>2
(I)]¼0.050, wR2 (all data)¼
s
0.117, largest diff. peak and hole¼0.696/ꢀ0.378 e Aꢀ3
.
Crystallographic data (excluding structure factors) for the
structures reported in this work have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation no. CCDC 876005 (4k) Copies of the data can be obtained free
of charge on application to The Director, CCDC, 12 Union Road,
Cambridge DB2 1EZ, UK (Fax: int. codeþ(1223)336-033; e-mail:
deposit@ccdc.cam.ac.uk).
4.3.14. (E)-1-[2-Isopropyl-5(phenylamino)-1,3,4-thiadiazol-3(2H)-
yl]-2,3-diphenylprop-2-en-1-one (4n). Colourless crystals (0.323 g,
76%), mp 134e135 ꢁC (ethanol). IR (KBr)
n
¼3310 (NH), 3070
(AreCH), 2980 (AlieCH), 1670 (CO), 1620 (C]N), 1600 (AreC]C)
cmꢀ1; 1H NMR (CDCl3): dH¼7.45 (br, 1H, NH), 7.40e7.29 (m, 6H,
AreH), 7.28e7.00 (m, 6H, AreH), 6.93e6.90 (m, 4H, AreCH),
6.53e6.52 (m, 1H, thiadiazoleeCH), 2.42e2.44 (m, 1H, CH), 0.90 (d,
J¼6.7 Hz, 6H, 2CH3); 13C NMR (CDCl3): dC¼167.4 (CO), 153.8 (thia-
diazole C-5), 136.6, 135.2, 135.1, 134.7 (AreC), 131.7, 129.7, 128.7,
128.6, 128.2, 127.9, 127.6, 127.3, 127.0, 126.6 (Ar CH), 67.2 (thiadia-
zole CH), 31.9 (CH), 17.3 (CH3); MS (EI): m/z¼427 (Mþ, 20), 384 (11),
292 (14), 219 (62), 207 (58),179 (91),177 (100),150 (61),118 (42), 77
(54). Anal. Calcd for C26H25N3OS (427.56): C, 73.04; H, 5.89; N, 9.83;
S, 7.50. Found: C, 73.22; H, 5.98; N, 10.02; S, 7.35.
Supplementary data
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.07.063.
References and notes
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