From tetrazoles via hydrazonoyl chlorides to 1,3,4-thiadiazole oligomers

Article abstract of DOI:10.1016/S0040-4039(00)01505-7

5-Substituted tetrazoles react rapidly with Appel salt 1 at room temperature to give hydrazonoyl chlorides (14) in high yield. 5-Aminotetrazole reacts further to give an extended bis-imine (6) which, with triphenylphosphine at room temperature, rapidly gives 1,3,4-thiadiazoles 15 and 17. The mono-imines 14 react similarly to give simpler thiadiazoles 18 in high yield. By repetition of the tetrazole formation and Appel salt-triphenylphosphine sequence, these 2-cyanothiadiazoles 18 are converted in high yield into thiadiazole dimers and trimers 21, n = 1 and 2. These reactions are explained mechanistically. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01505-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9407–9411
From tetrazoles via hydrazonoyl chlorides to
1,3,4-thiadiazole oligomers†
Van-Duc Le, Charles W. Rees* and Sivaprasad Sivadasan
Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London,
SW7 2AY, UK
Received 21 August 2000; revised 30 August 2000; accepted 5 September 2000
Abstract
5-Substituted tetrazoles react rapidly with Appel salt 1 at room temperature to give hydrazonoyl
chlorides (14) in high yield. 5-Aminotetrazole reacts further to give an extended bis-imine (6) which, with
triphenylphosphine at room temperature, rapidly gives 1,3,4-thiadiazoles 15 and 17. The mono-imines 14
react similarly to give simpler thiadiazoles 18 in high yield. By repetition of the tetrazole formation and
Appel salt–triphenylphosphine sequence, these 2-cyanothiadiazoles 18 are converted in high yield into
thiadiazole dimers and trimers 21, n=1 and 2. These reactions are explained mechanistically. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: tetrazoles; nitriles; 1,3,4-thiadiazoles; oligomers.
5-Arylimino-4-chloro-1,2,3-dithiazoles 2 are stable yellow crystalline solids readily prepared in
high yield from anilines and 4,5-dichloro-1,2,3-dithiazolium chloride 1 (‘Appel salt’) itself readily
available from chloroacetonitrile and disulphur dichloride.1 Formation of the iminodithiazoles 2
is a general reaction which we have extended to a wide range of aromatic and heteroaromatic
amines because of the synthetic versatility of 2.2 This derives from their reactivity towards inter-
and intra-molecular nucleophilic attack at S-1, S-2 and C-5 of the dithiazole ring driven by
regeneration of the latent cyano group.3 Some of these reactions transform the dithiazole ring
only, such as treatment with triphenylphosphine in CH2Cl2 at room temperature to give the
cyanothioformanilides 3 in high yield,4 whilst others involve cyclisation onto the adjacent
aromatic ring.2 However treatment of 5-aminotetrazole monohydrate 4 with Appel salt (1.1
equiv.) under standard conditions (with pyridine in CH2Cl2 at room temperature) took a very
different course, giving none of the corresponding imine 5. Nitrogen was evolved from the
unusually complex reaction mixture from which a very low yield of the unexpected product 6
* Corresponding author. Tel: +44-207-594-5768; fax: +44-207-594-5800; e-mail: c.rees@ic.ac.uk
†
Dedicated with admiration and affection to Harry H. Wasserman on the occasion of his 80th birthday.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01505-7

9408
(8%) was isolated as long red needles. Its structure was deduced from analysis, spectroscopy and
mechanistic considerations (Scheme 1) and was confirmed by X-ray crystallography.5 This
product is derived from 1 mol of tetrazole 4 and 2 mol of Appel salt 1 with loss of N2 and 3
HCl; with 2 equiv. of 1, its yield rose to 20% but was not increased further with more Appel salt.
Scheme 1.
It is possible that 6 is formed from 1 and 4 via the normal iminodithiazole 5, but this appears
unlikely since several other 5-substituted tetrazoles 11 (see below) react entirely analogously with
Appel salt at N-2. 5-Amino-2-methyltetrazole, with its N-2 position blocked, reacts normally at
the exocyclic amino group to give a high yield (89%) of the stable iminodithiazole 7.
We therefore propose that 1 and 4 give the 2,5-disubstituted tetrazole 8, which then reacts
with more Appel salt to give 9. With the strongly electron-withdrawing dithiazolium group on
N-2, 9 could equilibrate with the stabilised diazonium tautomer 10 which with chloride would
give the trichloro compound 6 isolated. X-Ray crystallography5 shows 6 to be planar with the
configuration shown and extensively delocalised (6l6a). This accounts for its deep red colour
and the observed inertness of the central ‘imidoyl’ chloride towards hydrolysis.
To seek support for the mechanism of Scheme 1 we investigated the reaction of a series of
tetrazoles 11, where the amino group is replaced by substituents inert towards Appel salt. The
5-substituted tetrazoles 11a–h (Table 1) were prepared in high yields by the addition of azide
ions to RꢀCN.6 If these tetrazoles react with 1 in the same way as the 5-amino compound 4, the

9409
dithiazolium salts 12 (Scheme 2) would be formed; since 12 cannot react further with Appel salt
it could equilibrate directly with the stabilised diazonium chloride 13 and hence give the
hydrazonoyl chlorides 14 analogous to 6. This is exactly what was observed with all the
tetrazoles 11a–h upon treatment with 1 (1.1 equiv.) in CH2Cl2 at room temperature; the products
14 were isolated in high yield as yellow to red solids (Table 1). These were stable except for the
5-phenoxy compound 14f, which decomposed rapidly in the solid state, and the 5-chloroethyl
compound 14h, which decomposed slowly. Structures 14 were based on analytical and spectro-
scopic data and on their conversion into 1,3,4-thiadiazoles 18 (below).
Table 1
Synthesis of hydrazonoyl chlorides 14 and 5-substituted 2-cyano-1,3,4-thiadiazoles 18
R
11
14 yields (%)
18 yields (%)
Ph
11a
11b
11c
11d
11e
11f
11g
11h
14a (87)
14b (94)
14c (76)
14d (95)
14e (86)
14f (56)
14g (78)
14h (75)
18a (80)
18b (99)
18c (72)
18d (92)
18e (76)
18f (75)
18g (73)
18h (90)
4-MeOC6H4
4-NCC6H4
4-O2NC6H4
2-Thienyl
PhO
MeS
ClCH2CH2
Scheme 2.
Although iminodithiazoles like 2 are thermally very stable, the red solution of bis-iminodithi-
azole 6 in warm DMSO slowly faded to yellow; the change was complete in 4 h at 50°C and a
yellow crystalline product 15 (Scheme 3) was isolated (25%). The presence of a conjugated cyano
group and the loss of the elements of SCl2 suggested that one of the dithiazole rings had been
opened, probably by nucleophilic attack by DMSO, especially since 6 was stable in CH2Cl2,
acetone, ethanol and chloroform at temperatures above 50°C. Attack on sulphur in the
appropriate dithiazole ring (Scheme 3) will generate a cyano group and nucleophilic sulphur
suitably placed (16) to cyclise to a cyano-1,3,4-thiadiazole; this suggested structure 15 for the
yellow product, and X-ray crystallography confirmed the configuration shown.5 A thiophile
stronger than DMSO should be more effective in this reaction; as mentioned above Ph3P rapidly
converts iminodithiazole 2 into cyanothioformamides 3 under very mild conditions. Bis-

9410
iminodithiazole 6 was therefore treated similarly; after 30 min it gave the same yellow product
15 (25%) plus the analogous orange cyanothioformamide 17 (20%). The latter presumably arose
from opening of the second dithiazole ring in 6 by PPh3, and indeed reaction of 6 with excess
of PPh3 (5 equiv.) gave 17 (85%) exclusively (Scheme 3). Triphenylphosphine oxide and sulphide
were also isolated in almost quantitative yield in accord with a previously proposed mechanism.4
Scheme 3.
The hydrazonoyl chlorides 14, from 2-substituted tetrazoles and Appel salt 1, responded in
exactly the same way to attack by PPh3. With 2 equiv. of PPh3 in CH2Cl2 at room temperature
for 15 min, compounds 14a–h all gave the corresponding 5-substituted-2-cyano-1,3,4-thiadi-
azoles 18, together with Ph3PꢁO and Ph3PꢁS, in high yields (Table 1), presumably by the same
mechanism as before (Scheme 3). This transformation provides good support for the structures
assigned to 14. The sequence of reactions, shown in Table 1, provides a very mild, high-yielding
synthesis of 1,3,4-thiadiazoles 18 from nitriles via the tetrazoles 11 and dithiazoles 14. This new
route has the useful feature of directly giving the reactive 2-cyano derivatives, which are rare
1,3,4-thiadiazole derivatives only made before by multi-step processes.7 Furthermore, the
starting cyanide, RCN, is converted into a new cyanide 18 and so the sequence of Table 1 can
be repeated to give a series of unsymmetrical thiadiazole oligomers of precisely known structure,
with a cyano group at one end and various groups, including strong electron donors, at the
other. So far we have shown (Table 2) that this route gives high yields of the highly fluorescent
dimers 21, n=1, and trimers 21, n=2 (Table 2). A few such trimers have been made before by
classical 1,3,4-thiadiazole ring forming sequences.8

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Table 2
Synthesis of dimers and trimers of 1,3,4-thiadiazoles
19 yields (%)
20 yields (%)
R=SMe
21 yields (%)
R=SMe
R=Ph
R=SMe
R=Ph
R=Ph
n=1
n=2
94
92
97
89
88
90
84
87
80
64
85
79
The structure of trimer 21 (R=SMe, n=2) was confirmed by X-ray diffraction; in the crystal
the heterocyclic rings are nearly coplanar, with the all-anti orientation shown. Well-defined
conjugated oligomers, related to polythiophenes, are important as active compounds in field
effect transistors and light-modulating and light-emitting devices with properties that can
surpass those of the corresponding polymers.9
Acknowledgements
We thank the SERC and MDL Information System (UK) Ltd for financial support, Professor
D. J. Williams and Dr. A. J. P. White for X-ray crystallography and the Wolfson Foundation
for establishing the Wolfson Center for Organic Chemistry in Medical Science at Imperial
College.
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1984; Vol. 5, p. 825 and Butler, R. N. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.; Rees, C. W.;
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