A facile and convenient method for the synthesis of bis-hydrazonoyl halides and bis-(1,3,4-thiadiazol-3-ylphenoxy)ethers

Article abstract of DOI:10.1080/104265090517226

New bis(thiadiazole) derivatives 7a-m were prepared in good yields by the reaction of the appropriate hydrazonoyl halides 4a-e with the bis-Schiff bases 9a-c. Similarly, the bis(thiadiazole) derivatives 17a-g were prepared by the reaction of the novel bis

Full text of DOI:10.1080/104265090517226

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Phosphorus, Sulfur, and Silicon
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A Facile and Convenient
Method for the Synthesis
of Bis-Hydrazonoyl Halides
and Bis-(1,3,4-Thiadiazol-3-
ylphenoxy)Ethers
Ashraf A. Abbas a & Nora M. Rateb a
a Chemistry Department , Faculty of Science, Cairo
University , Giza, Egypt
Published online: 21 Dec 2010.
To cite this article: Ashraf A. Abbas & Nora M. Rateb (2005) A Facile and Convenient
Method for the Synthesis of Bis-Hydrazonoyl Halides and Bis-(1,3,4-Thiadiazol-3-
ylphenoxy)Ethers, Phosphorus, Sulfur, and Silicon and the Related Elements, 180:2,
497-511, DOI: 10.1080/104265090517226
To link to this article: http://dx.doi.org/10.1080/104265090517226
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Phosphorus, Sulfur, and Silicon, 180:497–511, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090517226
A Facile and Convenient Method for the Synthesis
of Bis-Hydrazonoyl Halides and
Bis-(1,3,4-Thiadiazol-3-ylphenoxy)Ethers
Ashraf A. Abbas
Nora M. Rateb
Chemistry Department, Faculty of Science, Cairo University,
Giza, Egypt
New bis(thiadiazole) derivatives 7a–m were prepared in good yields by the reaction
of the appropriate hydrazonoyl halides 4a–e with the bis-Schiff bases 9a–c. Sim-
ilarly, the bis(thiadiazole) derivatives 17a–g were prepared by the reaction of the
novel bis-hydrazonoyl halides 13a–d with schiff bases 3a–d.
Keywords Bis-thiadiazol(phenoxy) alkanes; bis-hydrazonoyl halides; bis-aldehydes
INTRODUCTION
There is an intensive development in the synthesis of new derivatives
of thiazdiazole designed for uses ranging from routine to sophisti-
cated applications. Various series of thiadiazoles and their annelated
derivatives are reported to have diverse biological activities as antibac-
terial,1−4 antimicrobial,5,6 antifirinolytic and antiinflammatory,7
antihistamine agents and muscarinic agonists.8 In addition, some
thiadiazole derivatives are useful as inhibitors of the neutral
endopeptidase9 carbonic anhydrase,10 anticarcenogenic11 and kainic
acid neurocytotoxicity.12 Also, some substituted thiadiazoles are used
as corrosion inhibitor for copper,13 complexing agent for Hg14 as well as
additives to improve the properties of many lubricating greases and
oils.15−17 Recently, bis(compounds) attracted the attention of a large
group of authors due to their successful utility as building units
for many chain polymers.18−23 The biological activity of natural and
synthetic compounds increases as the molecular symmetry increases.24
This is based on the above facts and with continuation of our interest
Received May 11, 2004; accepted in inal form July 25, 2004.
Address correspondence to A. A. Abbas Chemistry Department, Faculty of Science,
Cairo University, Giza, Egypt. E-mail: ashrafaa50@yahoo.com
497

498
A. A. Abbas and N. M. Rateb
in the synthesis of novel bis-heterocycles.25−27 The present work
investigates the synthesis of some new bis-1,3,4-thiadiazoles as well as
novel bis-hydrazonoyl halides as key intermediates for the synthesis
of some new bis-heterocycles.
RESULTS AND DISCUSSION
We constructed the new bis(1,3,4-thiadiazol-5-aminobenzylidine-
phenoxy) alkanes 7a–m by two strategies outlined in Scheme 1. In the
first strategy, we investigated the synthesis of the bis-compounds 7a–m
using p-hydroxybenzaldehyde (1) as starting material. Thus, conden-
staion of latter compound with hydrazincarbodithioate (2) in isopropyl
SCHEME 1 Synthesis of bis(1,3,4-thiadiazol-5-aminobenzylidinephenoxy)
alkanes 9a–m from p-hydroxybenzaldehyde.

Synthesis of Bis(thiadiazole) Derivatives
499
alcohol, afforded exclusively the Schiff base 3 in good to excellent yields.
Compound 3 consequently reacted with hydrazonoyl halides 4a–c and
gave the corresponding 2-p-hydroxybenzaldehydehydrazono-3-phenyl-
5-substituted-2,3-dihydro-1,3,4-thiadiazoles 5a–c in 80–90% yields. We
tried several attempts to react different derivatives of thiadiazoles 5a–
c with 1,ω-dibromoalkanes 6a–c in different basic mediums [EtONa,
KOH/DMF, K2CO3/DMF) to obtain the target bis heterocycles 7a, e,
and g in good yields, but unfortunately all attempts lead to the for-
mation of an oily residue that cannot easily be handled with the for-
mation of minor products (2∼3% 1H NMR and TLC) of 7a, e, and
g. In view of the low yields of the above strategy, we tried a second
route. Thus, condensation of 1,ω-bis(4-formaylphenoxy)alkanes 8a–c
(obtained by reaction of 1 with 1,ω-dibromoalkanes in basic medium)
with 2 in isopropyl alcohol, furnished the corresponding bis-Schiff bases
9a–c in 70–90% yields. The reaction of equimolecular amounts of C-
ethoxycarbonyl-N-phenylhydrazonoyl chloride (4a) with 9a in ethano-
lic triethylamine solution afforded 7a which was assigned as bis-(1,3,4-
thiadiazole-5-aminobenzylidinephenoxy)alkane based on the spectral
and elemental analysis data of the reaction product. The 1H NMR spec-
trum of compound 7a showed signals at δ 1.3 (t, 6H, J= 6Hz, CH3), 4.40
(q, 4H, J= 7.6Hz, 7.6Hz, CH2CH3), 4.48 (s, 4H, OCH2), 7.06–8.40 (m,
20H, ArH’s and CH N); IR spectrum also revealed absorption bands
at 1742 and 1712 (cm−1) for (2 CO ester). Similarly, the hydrazonoyl
halides 4b–e reacted with compounds 9a–c to furnish the correspond-
ing novel bis(thiadiazole) derivatives 7a–m in 60–85% yields. Our ef-
forts were also extended to include the synthesis of new derivatives of
bis-thiadiazole (2-arylaldehydehydrazono-3-phenoxy)ethers where the
phenoxy alkanes moiety are connected to the position 3 in the thiadia-
zole ring instead of position 2 as in 7a–m. For this purpose we choose
1,ω-bis(2-aminophenoxy)alkane hydrochloride 10a, b as starting mate-
rial as depicted in Scheme 2. Thus, diazotization of the diamine dihy-
drochloride 10a, b with sodium nitrite in hydrochloric acid gave the cor-
responding bis-diazonium salts 11a, b which subsequently reacted with
the sulphonium bromides 12a, b (obtained by reacting arylphenacylbro-
mide with dimethylsulphide in absolute ethanol) in ethanolic sodium
acetate solution to afford the novel bis-hydrazonoyl halides 13a–d in
60–75% yields. By analogy and under the same conditions, the reaction
of bis-hydrazonoyl halides 13a–d with methylcarbodithioate deriva-
tives 3b–d, afforded the target bis-thiadiazole derivatives 17a–f in 50–
65% yields.
It is noteworthy that the formation of the bis(thiadiazole) derivatives
can proceed either by initial addition of the thiol tautomer 3 to the inter-
mediate 14, formed in situ by treatment of hydrazonoyl bromid 13 with

500
A. A. Abbas and N. M. Rateb
SCHEME 2 Synthesis of bis-thiadiazole (2-arylaldehydehydrazono-3-
phenoxy)ethers 17a–g from bis-amines.
TEA (which can exist in the mesomeric forms 14a and 14b)28 to give
the intermediate 15 which undergoes nucleophilic cyclization to yield
16. This affords 17 by loss of methyl mercaptan or by 1,3 cycloaddition
of 14b to the C S of 3 to give 16 directly29,30 (Scheme 2). By the same
mechanism, bis(thiadiazole) derivatives 7a–m can be obtained.

Synthesis of Bis(thiadiazole) Derivatives
501
The structures of all compounds were confirmed by IR, 1H NMR
and elemental analyses data. From the IR and 1H NMR spectra of
compounds 13a–d it could be concluded that compounds 13a–d exist
exclusively in the hydrazone form due to the following facts: (a) the ab-
sence of signals characteristic for the methine protons in their 1H NMR
spectra (b) the presence of NH absorption near ν = 3325 (cm−1) in their
IR spectra, and (c) the fact that the hydrazone is the most stable form
whenever condensation occurs at a methylene group.25
In conclusion, we succeeded to prepare new derivatives of
bis(thiadiazole) ring systems using bis(aldehydes) and bis(diamines)
and we prepared novel bis(hydrazonoyl halides) which are consid-
ered key intermediates for the synthesis of a wide variety of new
bis(heterocycles) of expected useful applications.31−33 The utility of
these new bis(hydrazonoyl halides) for preparing new ring systems are
now in progress.
EXPERIMENTAL
All melting points were determined on an electrothermal apparatus and
are uncorrected. IR spectra were recorded in (KBr disk) on a Bruker,
vector 22, Germany or on a Shimadzu FT-IR 8201 PC spectrophotome-
1
ter. H NMR spectra were recorded in CDCl3 and (CD3)2SO on a Var-
ian Gemini 200 MHz or on a Varian Mercury 300 MHz spectrometer
and shifts were expressed in δ units using tetramethylsilane (TMS)
as internal reference. Mass spectra were recorded on Hewlett-Packard
(HP) 5988A (EI, 15 eV). 1,2-Dibromoethane, 1,3-diaminopropane and
1,4-dibromobutane were used (from Aldrich). Compounds 2,34 3a–d,35
4a–c,36−40 8a–c,41 10a,42 10b,43 were prepared as reported.
Synthesis of Bis Schiff Bases 9a–c
General Procedure
A mixture of hydrazine carbodithioate 2 (0.01 mole) and the appro-
priate aldehydes 8a–c (0.005 mole) were stirred in isopropyl alcohol
(20 mL) at room temperature for 2 hr. The solid was obtained and col-
lected by filtration and crystallized from acetic acid as pale yellow crys-
tals to give 9a–c respectively.
Bis Methyl Carbodithioate 9a
With the use of the general procedure, reaction of 2 with 8a gave 9a
1
in (85%) yield, m.p. 188–90◦C. IR (cm−1) 3448, 3131 (NH); H NMR

502
A. A. Abbas and N. M. Rateb
(DMSO) δ 2.48 (s, 6H, SCH3), 4.43 (s, 4H, OCH2), 7.05 (d, 4H, J= 8.7
Hz, ArH’s), 7.65 (d, 4H, J= 8.7 Hz, ArH’s), 8.20 (s, 2H, CH N) 12.84 (s,
2H, NH). Calcd. for C20H22N4O2S4 (478.68): C, 50.18; H, 4.63; N, 11.70;
S, 26.79. Found: C, 50.30, H, 4.80; N, 11.60; S, 26.60.
Bis Methyl Carbodihtioate 9b
With the use of the general procedure, reaction of 2 with 8b gave 9b
1
in (78%) yield, m.p. 178–81◦C. IR (cm−1) 3449, 3116 (NH); H NMR
(DMSO) δ 2.38 (quintet, 2H, J= 8.4 Hz, OCH2CH2), 2.48 (s, 6H, SCH3),
4.18 (t, 4H, J= 8.4 Hz, OCH2), 7.03 (d, 4H, J= 9 Hz, ArH’s), 7.65 (d,
4H, J= 9 Hz, ArH’s), 8.17 (s, 2H, CH N) and 13.02 (s, 2H, NH). Calcd.
for C21H24N4O2S4 (492.71): C, 51.19; H, 4.91; N, 11.37; S, 26.03. Found:
C, 50.90, H, 4.70; N, 11.40; S, 26.10.
Bis Methyl Carbodithioate 9c
With the use of the general procedure, reaction of 2 with 8c gave 9c
1
in (83%) yield, m.p. 175–77◦C. IR (cm−1) 3448, 3101, (NH); H NMR
(DMSO) δ 1.88 (brs, 4H, OCH2CH2), 2.47 (s, 6H, SCH3), 4.08 (brs, 4H,
OCH2), 7.02 (d, 4H, J= 8.7 Hz, ArH’s), 7.65 (d, 4H, J= 8.7 Hz, ArH’s),
8.17 (s, 2H, CH N) and 13.16 (s, 2H, NH). Calcd. for C22H26N4O2S4
(506.73): C, 52.15; H, 5.17; N, 11.06; S, 25.31. Found: C, 52.30, H, 4.90;
N, 11.00; S, 25.20.
Synthesis of 2,3-Dihydro-1,3,4-thiadiazoles 5a–c and
bis(1,3,4-thiadiazol-5-aminobenzylidinephenoxy)alkanes
7a–m
General Procedure
To a stirred solution of the appropriate hydrazonoyl halides 4a–e
(0.01 mole) and 3a (0.01 mole) or the appropriate bis methyl carbod-
ithioate derivatives 9a–c (0.005 mole) in ethanol (20 ml) triethylamine
(0.01 mole) was added dropwise at room temperature and the reac-
tion mixture was further stirred for 2 hr. The solid was obtained, col-
lected, and crystallized from the proper solvent to give 5a–c and 7a–m,
respectively.
Synthesis of 2,3-Dihydro-1,3,4-thiadiazole 5a
With use of the general procedure, reaction of 3a with 4a gave crude
5a which was crystallized from ethanol as yellow crystals (65%) m.p.
1
157–60◦C. IR (cm−1) 3340 (OH), 1723 (C O). H NMR (CDCl3) δ 1.43

Synthesis of Bis(thiadiazole) Derivatives
503
(t, 3H, J= 6.5 Hz, CH2CH3), 4.49 (q, 2H, J= 6.9 Hz, CH2CH3), 5.45
(s, 1H, CH ), 6.83–7.98 (m, 9H, ArH’s), 8.31 (s, 1H, OH). Calcd. For:
C18H16N4O3S (368.42): C, 58.68: H, 4.38; N, 15.21; S, 8.70. Found: C,
58.50; H, 4.20; N, 15.00; S, 8.60.
Synthesis of 2,3-Dihydro-1,3,4-thiadiazole 5b
With use of the general procedure, reaction of 3a with 4b gave crude 5b
which was crystallized from acetic acid as orange crystals (75%) m.p.
1
229–30◦C. IR (cm−1) 3345 (OH), 1656 (C O). H NMR (DMSO) δ 2.35
(s, 3H, CH3), 6.82–8.07 (m, 10H, ArH’s and CH ), 10.01 (s, 1H, OH).
Calcd. for: C17H14N4O2S (338.39): C, 60.34; H, 4.17; N, 16.56; S, 9.48.
Found: C, 60.20; H, 4.00; N, 16.50; S, 9.30.
Synthesis of 2,3-Dihydro-1,3,4-thiadiazole 5c
With the use of the general procedure, reaction of 3a with 4c gave crude
5c which was crystallized from acetic acid as yellow crystals (85%) m.p.
248–50◦C. IR spectra (cm−1) 3340 (OH), 1645 (C O). 1H NMR (DMSO)
δ 6.85–8.39 (m, 15H, ArH’s and CH ), 10.06 (s, 1H, OH). Calcd. for:
C22H16N4O2S (400.46): C, 65.99: H, 4.03; N, 13.99; S, 8.01. Found: C,
65.60; H, 4.30; N, 14.00; S, 8.00.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7a
With the use of the general procedure, reaction of 4a with 9a gave crude
7a which was crystallized from acetic acid as yellow crystals (75%) m.p.
1
185–87◦C. IR (cm−1) 1742, 1712 (2 C O). H NMR (DMSO) δ 1.31 (t,
6H, J= 6 Hz, CH2CH3), 4.40 (q, 4H, J= 6 Hz, CH2CH3) 4.48 (s, 4H,
OCH2), 7.06–8.40 (m, 20H, ArH’s and CH ). Calcd. for C38H34N8O6S2
(762.87): C, 59.83; H, 4.49; N, 14.69; S, 8.41. Found: C, 59.70, H, 5.00;
N, 14.60; S, 8.30.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7b
With the use of the general procedure, reaction of 4b with 9a gave crude
7b which was crystallized from acetic acid as yellow crystals (85%) m.p.
235–37◦C. IR (cm−1) 1686, 1610 (2 C O). 1H NMR (DMSO) δ 2.51 (s, 6H,
CH3), 4.40 (s, 4H, OCH2), 7.08–8.44 (m, 20H, ArH’s and CH ). Calcd.

504
A. A. Abbas and N. M. Rateb
for C36H30N8O4S2 (702.82): C, 61.52; H, 4.30; N, 15.94; S, 9.12. Found:
C, 61.60, H, 4.40; N, 16.00; S, 9.00.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7c
With the use of the general procedure, reaction of 4c with 9a gave crude
7c which was crystallized from acetic acid as orange crystals (75%) m.p.
232–35◦C. IR (cm−1) 1640, 1610 (2 C O). 1H NMR (CDCl3) δ 4.41 (s, 4H,
OCH2), 6.99–8.39 (m, 30H, ArH’s and CH ). Calcd. for C46H34N8O4S2
(826.96): C, 66.81; H, 4.14; N, 13.55; S, 7.75. Found: C, 66.70, H, 4.10;
N, 13.50; S, 7.60.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7d
With the use of the general procedure, reaction of 4d with 9a gave crude
7d which was crystallized from DMF as orange crystals (70%) m.p. 260–
1
62◦C. IR (cm−1) 1620, 1615 (2 C O). H NMR (DMSO) δ 4.43 (s, 4H,
OCH2), 7.08–8.44 (m, 26H, ArH’s and CH ). Calcd. for C42H30N8O4S4
(839.01): C, 60.13; H, 3.60; N, 13.36; S, 15.29. Found: C, 59.90, H, 3.50;
N, 13.30; S, 15.20.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7e
With the use of the general procedure, reaction of 4a with 9b gave crude
7e which was crystallized from acetic acid as yellow crystals (85%) m.p.
1
130–33◦C. IR (cm−1) 1741, 1710 (2 C O). H NMR (DMSO) δ 1.31 (t,
6H, J= 6.9 Hz, CH2CH3), 2.19 (quintet, 2H, J= 7.2 Hz, OCH2CH2) 4.18
(t, 4H, J= 7.2 Hz, OCH2), 4.38 (q, 4H, J= 7.2 Hz, CH2CH3) 7.00–8.37
(m, 20H, ArH’s and CH ). Calcd. for C39H36N8O6S2 (776.90): C, 60.30;
H, 4.67; N, 14.42; S, 8.25. Found: C, 59.90, H, 4.80; N, 14.60; S, 8.30.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7f
With the use of the general procedure, reaction of 4b with 9b gave crude
7f which is crystallized from acetic acid as orange crystals (83%) m.p.
188–90◦C. IR (cm−1) 1683, 1620 (2 C O); Ms: m/z 716 (M+, 4.2%), 498
(19%), 396 (1.5%), 380 (1.4%), 266 (43%), 91 (100%), 77 (37%); 1H NMR
(DMSO) δ 2.17 (quintet, 2H, J= 6 Hz, OCH2CH2), 2.30 (s, 6H, CH3),
4.20 (t, 4H, J= 5.4Hz, OCH2), 7.01–8.37 (m, 20H, ArH’s and CH ).

Synthesis of Bis(thiadiazole) Derivatives
505
Calcd. for C37H32N8O4S2 (716.85): C, 62.08; H, 4.50; N, 15.63; S, 8.95.
Found: C, 61.80, H, 4.80; N, 15.60; S, 8.80.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7g
With the use of the general procedure, reaction of 4c with 9b gave crude
7g which was crystallized from acetic acid as yellow crystals (85%) m.p.
160–63◦C. IR (cm−1) 1638, 1612 (2 C O); Ms: m/z 840 (M+, 8.5%), 560
(12.47%), 533 (17%), 457 (13.9%), 281 (23.3%), 110 (100%), 105 (5.4%);
1H NMR (DMSO) δ 2.19 (quintet, 2H, J= 6.3 Hz, OCH2CH2) 4.24 (t,
4H, J= 6.3 Hz, OCH2), 7.01–8.39 (m, 30H, ArH’s and CH ). Calcd. for
C47H36N8O4S2 (840.99): C, 67.13; H, 4.31; N, 13.32; S, 7.63. Found: C,
67.00, H, 4.20; N, 13.10; S, 7.80.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7h
With the use of the general procedure, reaction of 4d with 9b gave crude
7h which was crystallized from acetic acid as red crystals (75%) m.p.
1
197–200◦C. IR (cm−1) 1684, 1610 (2 C O). H NMR (DMSO) δ 2.23
(quintet, 2H, J= 6.3 Hz, OCH2CH2) 4.24 (t, 4H, J= 6.3 Hz, OCH2),
7.01–8.39 (m, 26H, ArH’s and CH ). Calcd. for C43H32N8O4S4 (853.04):
C, 60.55; H, 3.78; N, 13.14; S, 15.04. Found: C, 60.30, H, 3.80; N, 13.00;
S, 14.90.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7i
With the use of the general procedure, reaction of 4e with 9b gave crude
7i which was crystallized from DMF as orange crystals (70%) m.p. 230–
32◦C. IR (cm−1) 1624, 1610 (2 C O). 1H NMR (DMSO) δ 2.23 (quintet,
2H, J= 6.3 Hz, OCH2CH2), 4.24 (t, 4H, J= 6.3 Hz, OCH2), 7.03–8.91
(m, 34H, ArH’s and CH ). Calcd. for C55H40N8O4S2 (941.11): C, 70.20;
H, 4.28; N, 11.91; S, 6.81. Found: C, 70.00, H, 4.10; N, 12.00; S, 6.90.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7j
With the use of the general procedure, reaction of 4a with 9c gave crude
7j which was crystallized from acetic acid as yellow crystals (82%) m.p.
1
180–83◦C. IR (cm−1) 1743, 1714, (2 C O). H NMR (DMSO) δ 1.38 (t,
6H, J= 7 Hz, CH2CH3), 1.94 (brs, 4H, OCH2CH2), 4.11 (brs, 4H, OCH2),

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A. A. Abbas and N. M. Rateb
4.42 (q, 4H, J= 7 Hz, CH2CH3) 7.02–8.42 (m, 20H, ArH’s and CH ).
Calcd. for C40H38N8O6S2 (790.93): C, 60.74; H, 4.84; N, 14.17; S, 8.11.
Found: C, 60.50, H, 4.80; N, 14.10; S, 8.00.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7k
With the use of the general procedure, reaction of 4b with 9c gave crude
7k which was crystallized from acetic acid as yellow crystals (83%) m.p.
215–18◦C. IR (cm−1) 1683, 1613, (2 C O). 1H NMR (DMSO) δ 1.92 (brs,
4H, OCH2CH2), 2.34 (s, 6H, CH3), 4.11 (brs, 4H, OCH2), 7.02–8.42 (m,
20H, ArH’s and CH ). Calcd. for C38H34N8O4S2 (730.87): C, 62.45; H,
4.69; N, 15.53; S, 8.77. Found: C, 62.30, H, 4.60; N, 15.30; S, 8.60.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7l
With the use of the general procedure, reaction of 4c with 9c gave crude
7l which was crystallized from acetic acid as orange crystals (73%) m.p.
225–27◦C. IR (cm−1) 1683, 1620, (2 C O). 1H NMR (DMSO) δ 1.92 (brs,
4H, OCH2CH2), 4.13 (brs, 4H, OCH2), 7.02–8.42 (m, 30H, ArH’s and
CH ). Calcd. for C48H38N8O4S2 (855.02): C, 67.43; H, 4.48; N, 13.11; S,
7.50. Found: C, 67.30, H, 4.30; N, 13.00; S, 7.50.
Synthesis of bis(1,3,4-Thiadiazol-5-aminobenzylidinephenoxy)
Alkane 7m
With the use of the general procedure, reaction of 4d with 9c gave
crude 7m which was crystallized from DMF as orange crystals (70%)
m.p. 245–48◦C. IR (cm−1) 1685, 1613, (2 C O); Ms: m/z 867 (M+, 14%),
581 (100%), 554 (26%), 463 (3.5%), 287 (4.7%); 1H NMR (DMSO) δ 1.93
(brs, 4H, OCH2CH2), 4.11 (brs, 4H, OCH2), 7.01–8.43 (m, 26H, ArH’s
and CH ). Calcd. for C44H34N8O4S4 (867.07): C, 60.95; H, 3.95; N, 12.92;
S, 14.79. Found: C, 60.80, H, 4.00; N, 13.00; S, 14.60.
Synthesis of Bis Hydrazonoyl Halides 13a–d
General Procedure
To a stirred solution of the appropriate dimethylsulfonium bromides
12a, b (0.01 mole) in ethanolic sodium acetate solution (20 mL ethanol,
4 g CH3COONa) a cold solution of the appropriate diazonium chlorides
11a, b (0.005 mole) (which was prepared by reaction of the appropriate
diamine dihydrochlorides 10a, b with concentrated HCl followed by

Synthesis of Bis(thiadiazole) Derivatives
507
addition of a solution of sodium nitite at 0–5◦C) was added dropwise
with stirring (0–5◦C) and the reaction mixture was stirred for 2–3 hr.
The solid obtained was collected and crystallized from acetic acid as
yellow-brown crystals to give 13a–d, respectively.
Bis Hydrazonoyl Halide 13a
With the use of the general procedure, reaction of 11a with 12a gave
1
13a in (80%) yield, m.p. 138◦C. IR (cm−1) 3325 (NH), 1651 (C O). H
NMR (CDCl3) δ 2.48 (quintet, 2H, J = 5.8 Hz, OCH2CH2), 4.41 (t, 4H,
J= 5.8Hz, OCH2), 6.94–8.04 (m, 18H, ArH’s) 9.08–9.18 (2s, 2H, NH).
Calcd. for C31H26Br2N4O4 (678.39): C, 54.89; H, 3.86; N, 8.26. Found:
C, 55.00, H, 4.10; N, 8.30.
Bis Hydrazonoyl Halide 13b
With the use of the general procedure, reaction of 11a with 12b gave
1
13b in (75%) yield, m.p. 170◦C. IR (cm−1) 3325 (NH), 1651 (C O). H
NMR (CDCl3) δ 2.49 (quintet, 2H, J= 5.4 Hz, OCH2CH2), 4.40 (m, 4H,
J= 5.4 Hz, OCH2), 6.94–8.04 (m, 16H, ArH’s) 9.09–9.19 (2s, 2H, NH).
Calcd. for C31H24Br2 Cl2N4O4 (747.28): C, 49.83; H, 3.24; N, 7.50. Found:
C, 50.00, H, 3.10; N, 7.30.
Bis Hydrazonoyl Halide 13c
With the use of the general procedure, reaction of 11b with 12a gave
13c in (73%) yield, m.p. 198◦C. IR (cm−1) 3325 (NH), 1658 (2 C O). 1H
NMR (CDCl3) δ 2.18 (brs, 4H, OCH2CH2), 4.24 (brs, 4H, OCH2), 6.94–
8.04 (m, 18H, ArH’s) 9.09–9.21 (2s, 2H, NH). Calcd. for C32H28Br2N4O4
(692.41): C, 55.51; H, 4.08; N, 8.09. Found: C, 55.30, H, 4.10; N, 8.00.
Bis Hydrazonoyl Halide 13d
With the use of the general procedure, reaction of 11b with 12b gave
13d in (75%) yield, m.p. 196–98◦C. IR (cm−1) 3302 (NH), 1666 (C O).
1H NMR (CDCl3) δ 2.17 (brs, 4H, OCH2CH2), 4.24 (brs, 4H, OCH2),
6.91–8.00 (m, 16H, ArH’s) 9.10–9.21 (2s, 2H, NH). Calcd. for C32H26Br2-
Cl2N4O4 (761.30): C, 50.49; H, 3.44; N, 7.36. Found: C, 50.30, H, 3.30;
N, 7.20.

508
A. A. Abbas and N. M. Rateb
Synthesis of Bis 1,3,4-Thiadiazoles 17a–g
General Procedure
To a stirred solution of the appropriate hydrazonoyl halides 13a–c
(0.005 mole) and the appropriate methyl carbodithioate derivatives 3b–
d (0.01 mole) in ethanol (20 mL) triethylamine (0.01 mole) was added
dropwise at room temperature and the reaction mixture was further
stireed for 2 hr. The solid was obtained, collected, and crystallized from
acetic acid as yellow-brown crystals to give 17a–g, respectively.
Bis 1,3,4-Thiadiazole 17a
With the use of the general procedure, reaction of 13a with 3b gave
17a in (55%) yield, m.p. 170–73◦C. IR (cm−1) 1635, 1605, (2 C O); Ms:
m/z 869 (M+, 3%), 764 (3%), 548 (23%), 536 (30%), 296 (100%); 1H NMR
(CDCl3) δ 2.05 (quintet, 2H, J= 6.3 Hz, OCH2CH2), 2.38 (s, 6H, CH3),
4.07 (t, 4H, J= 5.7 Hz, OCH2) 6.83–8.25 (m, 28H, ArH’s and CH )
Calcd. for C49H40N8O4S2 (869.04): C, 67.72; H, 4.64; N, 12.89; S, 7.38.
Found: C, 67.50, H, 4.60; N, 12.90; S, 7.30.
Bis 1,3,4-Thiadiazole 17b
With the use of the general procedure, reaction of 13a with 3c gave
1
17b in (49%) yield, m.p. 180–83◦C. IR (cm−1) 1635, 1613, (2 C O). H
NMR (CDCl3) δ 2.08 (quintet, 2H, J= 6.6 Hz, OCH2CH2), 4.07 (t, 4H,
J= 5.9 Hz, OCH2) and 6.81–8.25 (m, 28H, ArH’s and CH ) Calcd. for
C47H34F2N8O4S2 (876.97): C, 64.37; H, 3.91; N, 12.78; S, 7.31. Found:
C, 64.20, H, 4.00; N, 12.90; S, 7.20.
Bis 1,3,4-Thiadiazole 17c
With the use of the general procedure, reaction of 13b with 3d gave
17c in (45%) yield, m.p. 203–205◦C. IR (cm−1) 1635, 1605, (2 C O);
Ms: m/z 909 (M+, 5.8%), 567 (10%), 491 (8%), 447 (8.7%), 416 (14.5%),
341 (1.2%), 69 (100%); 1H NMR (DMSO) δ 1.98 (quintet, 2H, J= 6 Hz,
OCH2CH2), 4.07 (t, 4H, J= 5.7 Hz, OCH2) 6.93–8.24 (m, 28H, ArH’s
and CH ) Calcd. for C47H34Cl2N8O4S2 (909.88): C, 62.04; H, 3.77; N,
12.32; S, 7.05. Found: C, 61.90, H, 3.50; N, 12.20; S, 7.00.
Bis 1,3,4-Thiadiazole 17d
With the use of the general procedure, reaction of 13b with 3b gave
1
17d in (56%) yield, m.p. 180–82◦C. IR(cm−1) 1635, 1605, (2 C O). H

Synthesis of Bis(thiadiazole) Derivatives
509
NMR (CDCl3) δ 2.06 (quintet, 2H, J= 6.2 Hz, OCH2CH2), 2.38 (s, 6H,
CH3), 4.07 (t, 4H, J= 6.3 Hz, OCH2), 6.79–8.01 (m, 26H, ArH’s and
CH ). Calcd. for C49H38Cl2N8O4S2 (937.93): C, 62.75; H, 4.08; N, 11.95;
S, 6.84. Found: C, 62.70, H, 4.00; N, 12.00; S, 7.00.
Bis 1,3,4-Thiadiazole 17e
With the use of the general procedure, reaction of 13b with 3c gave
17e in (73%) yield, m.p. 210–12◦C. IR (cm−1) 1635, 1605, (2 C O).
1H NMR (CDCl3) δ 2.06 (quintet, 2H, J= 6.2 Hz, OCH2CH2), 4.07 (t,
4H, J= 5.6 Hz, OCH2), 6.65–8.23 (m, 26H, ArH’s and CH ). Calcd. for
C47H32Cl2F2N8O4S2 (945.86): C, 59.68; H, 3.41; N, 11.85; S, 6.78. Found:
C, 59.70, H, 3.20; N, 12.00; S, 6.90.
Bis 1,3,4-Thiadiazole 17f
With the use of the general procedure, reaction of 13c with 3c gave 17f
in (55%) yield, m.p. 209–10◦C. IR (cm−1) 1641, 1605, (2 C O). 1H NMR
(CDCl3) δ 1.68 (brs, 4H, OCH2CH2), 3.84 (brs, 4H, OCH2) 6.80–8.26 (m,
28H, ArH’s and CH ) Calcd. for C48H36F2N8O4S2 (891.00): C, 64.71; H,
4.07; N, 12.58; S, 7.20. Found: C, 64.60, H, 4.00; N, 12.30; S, 7.00.
Bis 1,3,4-Thiadiazole 17g
With the use of the general procedure, reaction 13c with 3b gave 17g
in (50%) yield, m.p. 205–08◦C. IR (cm−1) 1635, 1605, (2 C O); Ms:
m/z 884 (M+1, 8%), 765 (11%), 562 (13%), 486 (19%), 471 (2.2%), 235
(100%); 1H NMR (CDCl3) δ 2.10 (brs, 4H, OCH2CH2), 2.57 (s, 6H, CH3),
4.25 (brs, 4H, OCH2), 7.20–8.68 (m, 28H, ArH’s and CH ) Calcd. for
C50H42N8O4S2 (883.07): C, 68.01; H, 4.79; N, 12.69; S, 7.26. Found: C,
67.90, H, 4.60; N, 12.50; S, 7.20.
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