Efficient synthesis of novel 2,3-dihydro-1,3,5,4-thiadiazaphosphole derivatives

Article abstract of DOI:10.1080/17415993.2016.1163698

ABSTRACT: The condensation of various thiosemicarbazones with methyl thiophene-2-carboximidate afforded the corresponding intermediates 2a–2h. Subsequent cyclization of the latter compounds with hexamethylphosphorous triamide constitutes a new route to the synthesis of novel highly functionalized thiadiazaphosphole derivatives 4a–4h. This method offers significant advantages such as efficiency, high yields and mild reaction conditions.

Full text of DOI:10.1080/17415993.2016.1163698

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Efficient synthesis of novel 2,3-dihydro-1,3,5,4-
thiadiazaphosphole derivatives
Monaem Balti & Mohamed Lotfi Efrit
To cite this article: Monaem Balti & Mohamed Lotfi Efrit (2016): Efficient synthesis of
novel 2,3-dihydro-1,3,5,4-thiadiazaphosphole derivatives, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2016.1163698
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Date: 01 April 2016, At: 09:03

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1163698
Efficient synthesis of novel
2
,3-dihydro-1,3,5,4-thiadiazaphosphole derivatives
Monaem Balti and Mohamed Lotfi Efrit
Department of Chemistry, Laboratory of Organic Synthesis and Heterocyclic Chemistry, College of Sciences at
Tunis, El Manar University, Tunis, Tunisia
ABSTRACT
ARTICLE HISTORY
The condensation of various thiosemicarbazones with methyl
thiophene-2-carboximidate afforded the corresponding intermedi-
ates 2a–2h. Subsequent cyclization of the latter compounds with
hexamethylphosphorous triamide constitutes a new route to the
synthesis of novel highly functionalized thiadiazaphosphole deriva-
tives 4a–4h. This method offers significant advantages such as effi-
ciency, high yields and mild reaction conditions.
Received 2 December 2015
Accepted 6 March 2016
KEYWORDS
Thiosemicarbazones;
hexamethylphosphorous
triamide; iminoester;
thiadiazaphospholes
1. Introduction
Although heterocyclic compounds of phosphorus have received considerable attention
over the past three decades, there remain a number of interesting problems to be solved.
Thus, the nitrogen- and sulfur-containing heterophospholes, especially including an
[
N—P—N] unit, have been less studied. It was found that some of the target compounds are
useful not only as antibacterials [1] and cytoxic agents [1] but also in preparing two- and
three-coordinate phosphorus cations.[2] Some examples of these derivatives possessing
potent activity are shown in Figure 1.
Motivated by the aforementioned biological importance of these heterocyclic com-
pounds which include [N—P—N] units and as continuation with our previous work on the
synthesis of novel heterocyclic systems,[3–6] we report herein the synthesis of some new
thiadiazaphospholes derivatives starting from methyl thiophene-2-carboximidate. Some
characteristic properties of products have been also reported.
CONTACT Monaem Balti
baltimoneem@gmail.com
©
2016 Informa UK Limited, trading as Taylor & Francis Group

2
M. BALTI AND M. L. EFRIT
Figure 1. Synthetic route for some biologically active nitrogen- and sulfur-containing heterophos-
pholes.
2. Results and discussion
Iminoesters occupy a special position as important intermediates in synthesis because
they provide building blocks for several types of heterocyclic systems.[7] As a result of
the versatility of the title compounds as a synthetic entry point to fused heterocycles, we
first investigated their behavior in reaction with some thiosemicarbazones. Second, the
reactivity of the resulted intermediates 2a–2h toward thiadiazaphospholes was studied.
The starting materials for this work were easily prepared according to the reported
procedures. Methyl thiophene-2-carboximidate was synthesized by application of the
Pinner synthesis.[8,9] Passage of dry HCl gas into an ethereal solution of thiophene-2-
carbonitrile containing an equimolar amount of methanol for 1 h gave the hydrochloride
salt. This was isolated as a crystalline solid and treated with sodium bicarbonate solution
in ether at 0°C to provide free imidate in high overall yield (80%).
Thiosemicarbazones1a–1h, were synthesized in two steps. The first step was the
preparation of 4-phenylthiosemicarbazide in 79% yield by the reaction of phenylisoth-
iocyanate and hydrazine hydrate in ethanol at room temperature.[10] The reaction
of 4-phenylthiosemicarbazide with various aromatic aldehydes in the presence of few
drop of acetic acid (0.5 mL) at 79°C for 4 h leads to the corresponding 4-phenyl-3-
thiosemicarbazone derivatives in good yields (73–91%).
Straightforward reactions of iminoesters with hydrazine derivatives led us to presume
that analogous reactions are possible with thiosemicarbazones. In fact, the condensation
of 4-phenyl-3-thiosemicarbazones with methyl thiophene-2-carboximidate in absolute
ethanol under reflux resulted in the formation of the key intermediates 2a–2h. In order
to demonstrate the efficiency and generality of this protocol, we examined the reactions
of iminoester and various substituted thiosemicarbazones (Table 1). All substrates react
to give the corresponding products 2a–2h in good to excellent yields. We propose the
mechanism shown in Scheme 1. Conjugate addition of 1a–1h gives the intermediate A.
Elimination of the methoxy group provides compounds 2a–2h.
The chemical structures of compounds 2a–2h are in agreement with their spectral data.
−
1
−1
The IR spectrum exhibited absorption bands at 3280 cm (NH), and 1630 cm (C=N),
−
1
and the absence of an absorption band at 1265 cm attributed to the C=S moiety. The
1
H NMR analysis confirmed the formation of products 2a–2h and showed the presence
of new signals assigned to NH, CH=N, and the protons of the phenyl introduced by the

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. Proposed mechanism for the formation of compounds 2a–2h.
Table 1. Substrate scope studies
Entry
R1
Product
2a
Yield (%)a
79
1a
O
S
1b
2b
80
1
c
2c
77
74
O N
2
S
1
d
2d
O
O
NO2
1
e
f
O
S
2e
2f
81
78
H C
3
O
1
H C
3
N
H C
3
1
g
h
2g
2h
87
85
H CO
3
1
O N
2
aIsolated yield.
substituted thiosemicarbazones. In the 13C NMR spectra, we observed greater than 95%
disappearance of the signal around 52 ppm related to the methoxy group.
The key intermediates 2a–2h possess several reactive sites; in particular the N,N-
nucleophilic sites. They can partake in intermolecular condensation with electrophilic
reagents. The bisnucleophilic character of 2a–2h allows us to postulate that their reaction
with hexamethylphosphorous triamide could constitute an easy access in to a new series of
thiadiazaphospholes. Indeed, good yields of the title compounds have been obtained by the
reaction of the intermediates 2a–2h with hexamethylphosphorous triamide in dry toluene
under reflux (Scheme 2 and Table 2).

4
M. BALTI AND M. L. EFRIT
Scheme 2. Synthetic route for the title compounds 4a–4h.
Table 2. Substrate scope studies
Entry
Product
Yield (%)a
Product
Yield (%)a
2
2
2
2
2
2
2
2
a
b
c
d
e
f
3a
3b
3c
3d
3e
3f
87
86
81
87
87
83
85
81
4a
4b
4c
4d
4e
4f
82
87
84
89
81
79
90
83
g
h
3g
3h
4g
4h
aIsolated yield.
The formation of thiadiazaphospholes 4a–4h was confirmed by H, 13C, and 31P NMR
1
3
1
spectra and IR spectroscopy as well as elemental analysis. The P NMR spectra showed
the presence of a signal corresponding to the phosphonate moiety (P=S) at 80 ppm. The
−
1
−1
IR spectrum of 4a–4h showed absorption bands at 1645 and 1587 cm (C=N), 790 cm
−
1
(
P=S) and strong bands in the region of 921–947 cm indicating the presence of P-N
1
groups. The H NMR spectrum of compounds 4a–4h revealed the presence of two types of
methyl group protons in NMe with different chemical shifts. Furthermore, the Me group
2
protons of NMe moiety coupled with phosphorus and were split into a doublet. Further
2
1
support was obtained from the H NMR spectra, where it did not display signs of the NH
1
protons. On the other hand, the H NMR spectra exhibited resonances assigned to the
1
3
CH=N moiety appearing as a singlet at 8.21–8.47 ppm. The C NMR spectra of thidi-
azaphospholes displayed the characteristic signals of all carbons and revealed two signals
attributable to the carbons of P-N(CH ) of the two non-equivalent methyls of the NMe
3
2
2
group and a signal around 147 ppm attributed to the endocyclic C=N.
3. Conclusion
In summary, we have developed an efficient and general methodology for the synthesis of
novel thiadiazaphospholes derivatives through the reaction of various thiosemicarbazones
with methyl thiophene-2-carboximidate and cyclization of the obtained intermediates
with hexamethylphosphoro triamide. The possible biological activities of the synthesized
compounds are ongoing in our laboratory and will be reported in due course.
4
. Experimental section
.1. General
Melting points were measured with a Kofler hot-staged apparatus and are uncorrected. H,
4
1
3
1
13
P and C-NMR spectra were recorded with DMSO-d as the solvent on a Bruker-300
6

JOURNAL OF SULFUR CHEMISTRY
5
spectrometer. The chemical shifts are reported in ppm relative to TMS (internal reference)
1
13
31
for H and C-NMR and relative to 85% H PO (external reference) for P-NMR. The
3
4
1
coupling constants are reported in Hz. For the H-NMR, the multiplicities of signals are
indicated by the following abbreviations: s: singlet, d: doublet, t: triplet. Elemental anal-
yses were carried out on EI Elemental Vario EL apparatus. IR spectra were recorded on
a Nicolet IR200 spectrometer. The progress of the reactions was monitored by thin layer
chromatography (TLC).
4.2. Typical procedure for the synthesis of compounds (2a–2h)
A mixture of methyl thiophene-2-carboximidate (1.41 g, 0.01 mol) and appropriate
thiosemicarbazones (0.01 mol) dissolved in absolute ethanol (50 mL) was refluxed for
6
–8 h with continuous stirring. The solvent was evaporated under reduced pressure,
and then the solid was triturated with cold water and cold absolute ethanol, dried and
recrystallized from a mixture methanol-DMF (2:1).
ꢀ
4
.2.1. (E)-N -((E)-Furan-2-ylmethylene)-N-phenylcarbamohydrazonicthiophene-2-
carbimidic thioanhydride (2a)
White solid, yield 79%, mp 220–222°C; IR (ν , cm−1): 3280 and 3173 (NH), 3090 and
max
1
2
7
800 (CH, furan ring), 1667 and 1625 (C=N). H NMR (300 MHz, DMSO-d ): δH 6.66,
6
.04, 7.88 (3H, furan ring), 7.11, 7.34, 7.48 (3H, thiophene ring), 7.33 (t, 1H, J = 7.2 Hz,
ArH), 7.47 (dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.63 (d, 2H, J = 7.8 Hz, ArH), 8.02 (s,
1
3
1
H, CH=N), 9.19 (br s, NH). C NMR (125 MHz, DMSO-d ): δC 129.84, 131.45, 133.17
6
and 143.51 (thiophene ring), 140.87 (CH=N), 114.6, 117.25, 142.67 and 146.43 (furan
ring), 126.10, 128.60, 126.71 and 139.20 (phenyl), 147.22 (C=NH), 154.53 (C=N). Anal.
Calcd for C H N OS (354.44): C, 57.61; H, 3.98; N, 15.81%. Found: C, 57.63; H, 3.95;
1
7
14
4
2
N, 15.87%.
ꢀ
4
.2.2. (E)-N-Phenyl-N -((E)-thiophen-2-ylmethylene)carbamohydrazonicthiophene-2-
carbimidic thioanhydride (2b)
White solid, yield 80%, mp 243–245°C; IR (νmax, cm−1): 3267 and 3125 (NH), 2780 and
1
3
7
(
8
1
081 (CH, thiophene ring), 1661 and 1637 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.18, 7.31, 7.44, 7.55, 7.75 and 7.80 (6H, thiophene ring), 7.36 (t, 1H, J = 7.2 Hz, ArH), 7.51
dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.61 (d, 2H, J = 7.8 Hz, ArH), 8.52 (s, 1H, CH=N),
1
3
.89 (br s, NH). C NMR (125 MHz, DMSO-d ): δC 128.03, 129.80, 130.61, 131.12, 132.02,
6
33.21, 142.58 and 143.78 (thiophene ring), 139.17 (CH=N), 126.63, 126.81, 128.33 and
1
36.77 (phenyl), 148.01 (C=NH), 153.46 (C=N). Anal. Calcd for C H N S (370.50):
1
7
14 4 3
C, 55.11; H, 3.81; N, 15.12%. Found: C, 55.13; H, 3.76; N, 15.16%.
ꢀ
4
.2.3. (E)-N -((E)-(5-nitrothiophen-2-yl)methylene)-N-phenylcarbamohydrazonic
thiophene-2-carbimidic thioanhydride (2c)
White solid, yield 77%, mp 261–264°C; IR (νmax, cm−1): 3272 and 3143 (NH), 2783 and
1
3
7
2
097 (CH, thiophene ring), 1643 and 1611 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.22, 7.40, 7.59, 7.72 and 7.85 (5H, thiophene ring), 7.34 (t, 1H, J = 7.2 Hz, ArH), 7.55 (dd,
H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.67 (d, 2H, J = 7.8 Hz, ArH), 8.31 (s, 1H, CH=N), 9.06

6
M. BALTI AND M. L. EFRIT
(
br s, NH). 13C NMR (125 MHz, DMSO-d ): δC 127.80, 128.91, 130.62, 131.79, 132.93,
6
1
43.61 and 150.70 (thiophene ring), 143.3 (CH=N), 126.44, 126.12, 128.42 and 137.15
(
4
phenyl), 149.13 (C=NH), 154.03 (C=N). Anal. Calcd for C H N O S (415.50): C,
1
7
13
5
2 3
9.14; H, 3.15; N, 16.86%. Found: C, 49.19 H, 3.12; N, 16.91%.
ꢀ
4
.2.4. (E)-N -((E)-(6-Nitrobenzo[d][1,3]dioxol-5-yl)methylene)-N-
phenylcarbamohydrazonic thiophene-2-carbimidic thioanhydride (2d)
−
1
Yellow solid, yield 74%, mp 217–219°C; IR (νmax, cm ): 3283 and 3123 (NH), 2812 and
1
3
6
(
092 (CH, thiophene ring), 1656 and 1618 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.25 (s, 2H, CH ), 7.09, 7.37, 7.51 (3H, thiophene ring), 7.21 (t, 1H, J = 7.2 Hz, ArH), 7.37
2
dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.57 (d, 2H, J = 7.8 Hz, ArH), 7.61 (s, 1H, ArH),
1
3
8
.17 (s, 1H, CH=N), 8.52 (s, 1H, ArH), 9.21 (br s, NH). C NMR (125 MHz, DMSO-d ):
6
δC 104.20 (CH ), 128.77, 131.13, 132.95 and 143.23 (thiophene ring), 140.87 (CH=N),
2
1
(
5
28.42, 126.44, 126.12, 139.52, 143.04, 149.11 and 152.34 (Carom), 148.80 (C=NH), 155.12
C=N). Anal. Calcd for C H N O S (449.54): C, 58.78; H, 4.26; N, 15.58%. Found: C,
2
2
19
5
2 2
8.79 H, 4.19; N, 15.63%.
ꢀ
4
.2.5. (E)-N -((E)-4-(methylsulfonyl)benzylidene)-N-phenylcarbamohydrazonic
thiophene-2-carbimidic thioanhydride (2e)
White solid, yield 81%, mp 247–249°C; IR (νmax, cm−1): 3264 and 3150 (NH), 2793 and
1
3
3
7
060 (CH, thiophene ring), 1663 and 1631 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.22 (s, 3H, CH ), 7.10, 7.36, 7.47 (3H, thiophene ring), 7.24 (t, 1H, J = 7.2 Hz, ArH),
3
.39 (dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.63 (d, 2H, J = 7.8 Hz, ArH), 7.95 (d, 2H,
J = 8.4 Hz, ArH), 8.15 (d, 2H, J = 8.4 Hz, ArH), 8.22 (s, 1H, CH=N), 8.97 (br s, NH).
1
3
C NMR (125 MHz, DMSO-d ): δC 43.8 (CH ), 129.02, 131.24, 132.76 and 143.12 (thio-
6
3
phene ring), 141.02 (CH=N), 126.11, 126.73, 128.62, 128.70 and 139.44 (Carom), 149.30
(
C=NH), 156.03 (C=N). Anal. Calcd for C H N O S (442.57): C, 54.28; H, 4.10; N,
2
0
18
4
2 3
12.66%. Found: C, 54.35; H, 4.09; N, 12.73%.
ꢀ
4
.2.6. (E)-N -((E)-4-(Dimethylamino)benzylidene)-N-phenylcarbamohydrazonic
thiophene-2-carbimidic thioanhydride (2f)
Yellow solid, yield 78%, mp 198–200°C; IR (νmax, cm−1): 3281 and 3122 (NH), 2782 and
1
3
2
7
081 (CH, thiophene ring), 1668 and 1644 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.96 (s, 6H, 2CH ), 7.14, 7.36, 7.50 (3H, thiophene ring), 7.23 (t, 1H, J = 7.2 Hz, ArH),
3
.34 (dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.53 (d, 2H, J = 7.8 Hz, ArH), 7.59 (d, 2H,
1
3
J = 8 Hz, ArH), 7.83 (d, 2H, J = 8.4 Hz, ArH), 8.33 (s, 1H, CH=N), 9.17 (br s, NH).
C
NMR (125 MHz, DMSO-d ): δC 21.21 (CH ), 129.20, 131.11, 133.17 and 143.40 (thio-
6
3
phene ring), 143.11 (CH=N), 126.33, 127.80, 128.91, 129.24, 137.81 and 141.64 (Carom),
1
48.19 (C=NH), 153.56 (C=N). Anal. Calcd for C H N S (407.55): C, 61.89; H, 5.19;
2
1
21 5 2
N, 17.18%. Found: C, 61.83; H, 5.22; N, 17.15%.
4.2.7. (E)-N’-((E)-4-Methoxybenzylidene)-N-phenylcarbamohydrazonicthiophene-2-
carbimidicthioanhydride (2g)
White solid, yield 87%, mp 187–189°C; IR (νmax, cm−1): 3287 and 3144 (NH), 2796 and
1
3
3
065 (CH, thiophene ring), 1659 and 1633 (C=N). H NMR (300 MHz, DMSO-d ): δH
6
.86 (s, 3H, OCH ), 6.86 (d, 2H, J = 8.8 Hz, ArH), 7.11, 7.36, 7.49 (3H, thiophene ring),
3

JOURNAL OF SULFUR CHEMISTRY
7
7
.22 (t, 1H, J = 7.2 Hz, ArH), 7.37 (dd, 2H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.45 (d, 2H,
13
J = 8.8 Hz, ArH), 7.51 (d, 2H, J = 7.8 Hz, ArH), 8.37 (s, 1H, CH=N), 9.07 (br s, NH). C
NMR (125 MHz, DMSO-d ): δC 55.44 (CH ), 129.82, 131.45, 133.27 and 143.50 (thio-
6
3
phene ring), 140.12 (CH=N), 125.32, 126.78, 128.6, 129.43, 137.53 and 159.45 (Carom),
1
49.12 (C=NH), 152.31 (C=N). Anal. Calcd for C H N OS (394.51): C, 60.89; H, 4.60;
2
0
18
4
2
N, 14.20%. Found: C, 60.86; H, 4.63; N, 14.19%.
ꢀ
4
.2.8. (E)-N -((E)-4-Nitrobenzylidene)-N-phenylcarbamohydrazonic
thiophene-2-carbimidic thioanhydride (2h)
−
1
Yellow solid, yield 85%, mp 267–269°C; IR (νmax, cm ): 3277 and 3132 (NH), 2801
1
and 3052 (CH, thiophene ring), 1664 and 1632 (C=N). H NMR (300 MHz, DMSO-
d ): δH 7.21, 7.33, 7.52 (3H, thiophene ring), 7.26 (t, 1H, J = 7.2 Hz, ArH), 7.41 (dd,
6
2
H, J = 7.8 Hz, J = 7.2 Hz, ArH), 7.57 (d, 2H, J = 7.8 Hz, ArH), 7.68 (d, J = 8.8 Hz, 2H,
13
ArH), 8.12 (d, J = 8.8 Hz, 2H, ArH), 8.16 (1H, s, CH=N), 9.23 (br s, NH). C NMR
(
(
1
125 MHz, DMSO-d ): δC 129.89, 131.32, 133.01 and 142.98 (thiophene ring), 144.11
6
CH=N), 126.78, 128.60, 129.44, 137.53, 142.31 and 151.65 (C
), 147.88 (C=NH),
arom
53.97 (C=N). Anal. Calcd for C H N O S (409.48): C, 55.73; H, 3.69; N, 17.10%.
1
9
15
5
2 2
Found: C, 55.72; H, 3.66; N, 17.17%.
4
.3. General synthetic procedure for thiadiazaphosphole derivatives
To a well-stirred solution of compounds (2a–2b) (2 mmol) in anhydrous toluene (15 mL)
was added hexamethylphosphoroustriamide (2 mmol). The mixture was heated under
reflux for 12 h. Silica gel TLC indicated the completion of the reaction. The solvent was
evaporated under reduced pressure, and the residue was purified on silica gel preparative
TLC using ethyl acetate as eluent.
A mixture of compounds (3a–3b) (1 mmol), S (5 mmol) and anhydrous toluene
10 mL) was refluxed for 4 h, and then cooled. The sulfur excess was filtered off, and the
8
(
solvent was removed under reduced pressure. Flash column chromatography on silica gel
using petroleum ether as eluant affords (4a–4b).
4.3.1. (E)-4-(Dimethylamino)-2-(((E)-furan-2-ylmethylene)hydrazono)-3-phenyl-6-
(
thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-sulfide (4a)
−
1
Whitesolid, yield 82%, mp 177–179°C; IR (νmax, cm ): 790 (P=S), 926 (P-N), 1645 and
1
3
1
2
587 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.31 (d, J = 5.2 Hz, 3H, NCH ),
6
PH
3
3
.51 (d, J = 5.2 Hz, 3H, NCH ), 6.62, 7.05, 7.90 (3H, furan ring), 7.21, 7.35, 7.61 (3H,
PH
3
thiophene ring), 7.22 (t, 1H, J = 7.4 Hz, ArH), 7.07 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH),
1
3
7
3
.44 (d, 2H, J = 7.8 Hz, ArH), 8.42 (s, 1H, CH=N). C NMR (125 MHz, DMSO-d ): δC
6
2
2
5.76 (d, J = 9.1 Hz, NCH ), 36.16 (d, J = 5.8 Hz, NCH ), 128.14, 130.95, 133.05
PC
3
PC
3
and 142.44 (thiophene ring), 143.17 (CH=N), 115.13, 117.27, 142.43 and 146.42 (furan
3
1
ring), 126.20, 128.01, 128.74 and 138.41 (phenyl), 144.72 and 161.08 (C=N). P NMR
(
121.5 MHz, DMSO-d ): δ 79.21.Anal. Calcd for C H N OPS (459.54): C, 49.66; H,
6 19 18 5 3
3.95; N, 15.24%. Found: C, 49.69; H, 3.91; N, 15.31%.

8
M. BALTI AND M. L. EFRIT
4
.3.2. (E)-4-(Dimethylamino)-3-phenyl-6-(thiophen-2-yl)-2-(((E)-thiophen-2-
ylmethylene) hydrazono)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-
sulfide (4b)
−
1
Whitesolid, yield 87%, mp 217–219°C; IR (νmax, cm ): 797 (P=S), 933 (P-N), 1648 and
1
3
1
591 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.38 (d, J = 5 Hz, 3H, NCH ), 2.52
6
PH
3
3
(
7
d, J = 5 Hz, 3H, NCH ), 7.10, 7.33, 7.40, 7.51, 7.67 and 7.78 (6H, thiophene ring),
PH
3
.29 (t, 1H, J = 7.4 Hz, ArH), 6.98 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.48 (d, 2H,
1
3
J = 7.8 Hz, ArH), 8.37 (s, 1H, CH=N). C NMR (125 MHz, DMSO-d ): δC 35. 61 (d,
6
2
2
J
= 3 Hz, NCH ), 36.12 (d, J = 7.3 Hz, NCH ), 128.14, 129.80, 130.42, 131.33,
PC
3
PC
3
1
32.11, 133.20, 142.50 and 143.24 (thiophene ring), 141.02 (CH=N), 125.6, 128.31, 130.17
31
and 133.50 (phenyl), 146.32 and 162.31 (C=N). P NMR (121.5 MHz, DMSO-d ): δ 80.01.
6
Anal. Calcd for C H N PS (475.60): C, 47.98; H, 3.81; N, 14.73%. Found: C, 47.92; H,
1
9
18
5
4
3
.87; N, 14.72%.
4
.3.3. (E)-4-(Dimethylamino)-2-(((E)-(5-nitrothiophen-2-yl)methylene)hydrazono)-3-
phenyl-6-(thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-
sulfide (4c)
−
1
White solid, yield 84%, mp 241–243°C; IR (νmax, cm ): 790 (P=S), 932 (P-N), 1652 and
1
3
1
584 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.34 (d, J = 5 Hz, 3H, NCH ), 2.48
6
PH
3
3
(
1
d, J = 4.9 Hz, 3H, NCH ), 7.19, 7.32, 7.53, 7.61 and 7.91 (5H, thiophene ring), 7.28 (t,
PH
3
H, J = 7.4 Hz, ArH), 7.33 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.47 (d, 2H, J = 7.8 Hz,
13 2
ArH), 8.21 (s, 1H, CH=N). C NMR (125 MHz, DMSO-d ): δC 36.06 (d, J = 6 Hz,
6
PC
2
NCH ), 36.12 (d, J = 7 Hz, NCH ), 128.11, 128.70, 130.16, 132.10, 133.23, 142.37,
3
PC
3
1
43.24 and 153.30 (thiophene ring), 139.93 (CH=N), 127.12, 128.32, 128.96, 129.54
31
and 135.22 (phenyl), 147.09 and 161.40 (C=N). P NMR (121.5 MHz, DMSO-d ): δ
6
7
7.92.Anal. Calcd for C H N O PS (520.59): C, 43.84; H, 3.29; N, 16.14%. Found: C,
19 17 6 2 4
4
3.85; H, 3.33; N, 16.20%.
4
.3.4. (E)-4-(Dimethylamino)-2-(((E)-(6-nitrobenzo[d][1,3]dioxol-5-yl)methylene)
hydrazono) -3-phenyl-6-(thiophen-2-yl)-2,3-dihydro-1,3,5,4-
thiadiazaphosphole-4-sulfide (4d)
−
1
Yellow solid, yield 89%, mp 291–293°C; IR (νmax, cm ): 794 (P=S), 930 (P-N), 1648 and
1
3
1
2
574 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.24 (d, J = 4.9 Hz, 3H, NCH ),
6
PH
3
3
.44 (d, J = 4.9 Hz, 3H, NCH ), 6.22 (s, 2H, CH ), 7.09, 7.35, 7.53 (3H, thiophene
PH
3
2
ring), 7.23 (t, 1H, J = 7.4 Hz, ArH), 7.37 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.52 (d,
1
3
2
(
H, J = 7.8 Hz, ArH), 7.61 (s, 1H, ArH), 8.33 (1H, s, CH=N), 8.53 (s, 1H, ArH). C NMR
2 2
125 MHz, DMSO-d ): δC 35.96 (d, J = 6.1 Hz, NCH ), 36.43 (d, J = 7 Hz, NCH ),
6
PC
3
PC
3
1
1
05.03 (CH ), 128.72, 131.21, 133.01 and 143.21 (thiophene ring), 142.23 (CH=N), 124.95,
2
31
26.52, 128.76, 140.87, 143.12, 150.28 and 152.14 (Carom), 148.54 and 159.88 (C=N).
P
NMR (121.5 MHz, DMSO-d ): δ 78.87.Anal. Calcd for C H N O PS (558.58): C, 47.31;
6
22 19
6
4
3
H, 3.43; N, 15.05%. Found: C, 47.34; H, 3.44; N, 15.09%.

JOURNAL OF SULFUR CHEMISTRY
9
4
.3.5. (E)-4-(Dimethylamino)-2-(((E)-4-(methylsulfonyl)benzylidene)hydrazono)-3-
phenyl-6-(thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-
sulfide (4e)
−
1
White solid, yield 81%, mp 195–197°C; IR (νmax, cm ): 792 (P=S), 928 (P-N), 1652
1
3
and 1575 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.41 (d, J = 5 Hz, 3H, NCH ),
6
PH
3
3
2
.55 (d, J = 4.9 Hz, 3H, NCH ), 3.18 (s, 3H, CH ), 7.08, 7.39, 7.62 (3H, thiophene
PH
3
3
ring), 7.28 (t, 1H, J = 7.4 Hz, ArH), 7.33 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.51
(
d, 2H, J = 7.8 Hz, ArH), 7.90 (d, 2H, J = 8.4 Hz, ArH), 8.11 (d, 2H, J = 8.4 Hz, ArH),
1
3
2
8
3
.21 (s, 1H, CH=N). C NMR (125 MHz, DMSO-d ): δC 35.32 (d, J = 6 Hz, NCH ),
6
PC
3
2
6.07 (d, J = 7.2 Hz, NCH ), 42.92 (CH ), 128.68, 132.03, 133.44 and 142.97 (thio-
PC
3
3
phene ring), 143.09 (CH=N), 125.93, 127.13, 128.44, 128.89, 137.74 and 140.53 (C
),
arom
3
1
1
45.78 and 159.05 (C=N). P NMR (121.5 MHz, DMSO-d ): δ 79.12.Anal. Calcd for
6
C H N O PS (547.66): C, 48.25; H, 4.05; N, 12.79%. Found: C, 48.22; H, 4.09; N,
2
2
22
5
2
4
1
2.84%.
4.3.6. (E)-4-(Dimethylamino)-2-(((E)-4-(dimethylamino)benzylidene)hydrazono)-3-
phenyl-6-(thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-sulfide (4f)
−
1
Yellow solid, yield 79%, mp 157–159°C; IR (νmax, cm ): 791 (P=S), 921 (P-N), 1663
1
3
and 1587 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.25 (d, J = 5 Hz, 3H, NCH ),
6
PH
3
3
2
.49 (d, J = 5 Hz, 3H, NCH ), 2.91 (s, 6H, 2CH ), 7.21, 7.41, 7.57 (3H, thiophene
PH
3
3
ring), 7.31 (t, 1H, J = 7.4 Hz, ArH), 7.41 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.57
(
d, 2H, J = 7.8 Hz, ArH), 8.38 (s, 1H, CH=N), 7.62 (d, 2H, J = 8 Hz, ArH), 7.79 (d,
1
3
2
H, J = 8.4 Hz, ArH). C NMR (125 MHz, DMSO-d ): δC 20.98 (CH ), 36.01 (d,
2
6
3
2
J
= 6.2 Hz, NCH ), 36.22 (d, J = 7 Hz, NCH ), 129.12, 131.31, 133.76 and 143.21
PC
3
PC
3
(
(
thiophene ring), 143.12 (CH=N), 125.75, 127.32, 128.15, 134.12, 140.87 and 142.55
31
C
), 147.31 and 160.21 (C=N). P NMR (121.5 MHz, DMSO-d ): δ 80.23.Anal. Calcd
arom
6
for C H N PS (512.64): C, 53.89; H, 4.92; N, 16.39%. Found: C, 53.92; H, 4.87; N,
2
3
25
6
3
1
6.44%.
4.3.7. (E)-4-(Dimethylamino)-2-(((E)-4-methoxybenzylidene)hydrazono)-3-phenyl-6-
(
thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-sulfide (4g)
−
1
White solid, yield 90%, mp 268–270°C; IR (νmax, cm ): 798 (P=S), 947 (P-N), 1656 and
1
3
1
2
7
565 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.22 (d, J = 4.9 Hz, 3H, NCH ),
6
PH
3
3
.55 (d, J = 5 Hz, 3H, NCH ), 3.75 (s, 3H, OCH ), 7.01 (d, 2H, J = 8.8 Hz, ArH), 7.16,
PH
3
3
.38, 7.58 (3H, thiophene ring), 7.25 (t, 1H, J = 7.4 Hz, ArH), 7.41 (dd, 2H, J = 7.8 Hz,
J = 7.4 Hz, ArH), 7.57 (d, 2H, J = 7.8 Hz, ArH), 7.61 (d, 2H, J = 8.8 Hz, ArH), 8.47 (s, 1H,
1
3
2
CH=N). C NMR (125 MHz, DMSO-d ): δC 35.77 (d, J = 6.2 Hz, NCH ), 36.24 (d,
6
PC
3
2
J
= 7 Hz, NCH ), 56.04 (CH ), 127.24, 132.33, 133.09 and 142.89 (thiophene ring),
PC
3
3
1
1
(
44.65 (CH=N), 125.98, 126.43, 129.32, 131.19 140.12 and 154.65 (C
), 147.66 and
arom
3
1
63.23 (C=N). P NMR (121.5 MHz, DMSO-d ): δ 75.98.Anal. Calcd for C H N OPS
6
22 22
5
3
499.60): C, 52.89; H, 4.44; N, 14.02%. Found: C, 52.94; H, 4.40; N, 14.09%.
4.3.8. (E)-4-(Dimethylamino)-2-(((E)-4-nitrobenzylidene)hydrazono)-3-phenyl-6-
(
thiophen-2-yl)-2,3-dihydro-1,3,5,4-thiadiazaphosphole-4-sulfide (4h)
−
1
Yellow solid, yield 83%, mp 231–233°C; IR (νmax, cm ): 789 (P=S), 927 (P-N), 1658 and
1
3
1
592 (C=N). H NMR (300 MHz, DMSO-d ): δH 2.29 (d, J = 5.2 Hz, 3H, NCH ),
6
PH
3

10
M. BALTI AND M. L. EFRIT
2
.51 (d, 3JPH = 5.2 Hz, 3H, NCH ), 7.27, 7.39, 7.58 (3H, thiophene ring), 7.29 (t, 1H,
3
J = 7.4 Hz, ArH), 7.35 (dd, 2H, J = 7.8 Hz, J = 7.4 Hz, ArH), 7.59 (d, 2H, J = 7.8 Hz,
ArH), 7.66 (d, J = 8.8 Hz, 2H, ArH), 8.10 (d, J = 8.8 Hz, 2H, ArH), 8.24 (s, 1H, CH=N).
1
3
2
2
C NMR (125 MHz, DMSO-d ): δC 35.93 (d, J = 6 Hz, NCH ), 36.67 (d, J = 7 Hz,
6
PC
3
PC
NCH ), 129.03, 131.43, 133.21 and 142.94 (thiophene ring), 143.73 (CH=N), 126.44,
3
3
1
1
28.43, 131.02, 138.12, 142.56 and 152.87 (Carom), 146.43 and 162.17 (C=N). P NMR
(121.5 MHz, DMSO-d ): δ 80.19.Anal. Calcd for C H N O PS (514.57): C, 49.02; H,
6
21 19
6
2
3
3.72; N, 16.33%. Found: C, 49.08; H, 3.67; N, 16.37%.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
The authors are greatly appreciative of the Tunisian Ministry of Higher Education and Scientific
Research for financial support.
References
[
1] El-Sayed AT. Synthesis and antibacterial activity of some new thiadiaza/triazaphospholes,
thiadiaza/triaza/tetrazaphosphinines and thiadiaza/tetrazaphosphepines containing 1,2,4-
triazinone moiety. Eur J Med Chem. 2009;44:4539–4546.
[
2] Burford N, Dipchand AI, Royan BW, White PS. Experimental evidence for comparable strength
of phosphorus-sulfur and phosphorus-nitrogen p.pi.-bonding within the heteronaphthalenic
framework: spectroscopic and structural studies of the 1,3,2-benzazathiaphospholium system
as a cation and as neutral halides. Inorg Chem. 1990;29:4938–4944.
[
[
[
[
3] Balti M, Dridi K, El Efrit ML. A simple access in one step to some new substituted pyrazolo-
and [1,2,4]triazolo[1,5-a]pyrimidines. Lett Org Chem. 2013;10:118–120.
4] Balti M, Dridi K, El Efrit ML. An efficient one-pot synthesis of some new substituted 1, 2, 3,
5
-thiatriazolidin-4-one 1,1-dioxides. Heterocycles. 2014;89:1483–1490.
5] Balti M, Hachicha M, El Efrit ML. An efficient synthetic route towards novel 3n-substituted
thieno[2,3-d]pyrimidines. Heterocycles. 2015;91:1455–1464.
6] Hachicha M, Balti M, Mrabet H, El Efrit ML. Simple and efficient synthesis of some novel
triazole sulfonamides. Heterocycles. 2015;91:1645–1653.
[
[
[
7] Patai S. The chemistry of amidines and imidates. New York: John Wiley; 1975.
8] Roger R, Neilson DG. The chemistry of imidates. Chem Rev. 1961;61:79–211.
9] Elpern B, Nachod FC. Absorption spectra and structure of some tetrazoles. J Am Chem Soc.
1
950;72:3379–3382.
[
10] Huang H, Chen Q, Ku X, et al. A series of α-heterocyclic carboxaldehyde thiosemicarbazones
inhibit topoisomerase IIα catalytic activity. J Med Chem. 2010;53:3048–3064.