PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
13
5
1
anodic oxidation to form the amidinate radical intermediate material, Figures S1–S58).
A, which isomerizes to the sulfur radical intermediate B.
then, there are two possible pathways leading to product 4a.
The first reaction pathway is an intramolecular radical-cas-
Conclusion
cade cyclization of B to generate the intermediate C; Then, In summary, we disclosed an environmentally friendly
further anodic oxidative deprotonation of the intermediate method for the synthesis of 1,2,4-thiadiazole synthesis via a
C would afford the final product 4a. The other pathway electrochemical oxidative N-S bond formation. Under
(
path b) is the further anodic oxidation of B to afford the exogenous-oxidant-free and metal catalyst-free electrochem-
ical oxidation conditions, the present approach works well
with a wide range of amidines and thioureas substrates to
afford a variety of 5-amino-1,2,4-thiadiazoles in excellent
yields in an undivided cell. Furthermore, this method pro-
formation of a di-radical species D, which forms the final
product 4a through intramolecular cyclization.
5
Experimental
vides a facile access to both N3,N -symmetrically and
3
5
N ,N -asymmetrically substituted 3,5-diamino-1,2,4- thiadia-
zole derivatives. Additionally, the proposed mechanism was
provided and further work needs to be done to elucidate
General information
Unless otherwise noted, all reagents, and solvents were pur-
chased from commercial suppliers and used without further the mechanism.
purification. The reactions were carried out under air. The
instrument for electrolysis is a dual display potentiostat
Funding
(DJS-292B) (made in China). The anodic electrode was
graphite rod (/ 6 mm) and cathodic electrode was platinum This work was supported by grants from the National Natural Science
Foundation of China (Grant No. 21762022).
plate (15 mm ꢀ 15 mm ꢀ 0.3 mm). Thin layer chromatog-
raphy (TLC) employed glass 0.25 mm silica gel plates. Flash
chromatography columns were packed with 200–300 mesh
ꢁ
silica gel in petroleum (bp. 60–90 C). 1H and 13 C NMR
References
data were recorded with Bruker Advance III (400 MHz)
[
1] (a) Mullican, M. D.; Wilson, M. W.; Conner, D. T.; Kostlan,
spectrometers with tetramethylsilane as an internal standard.
All chemical shifts (d) are reported in ppm and coupling
constants (J) in Hz. and DMSO (2.50 ppm for 1 H NMR,
C. R.; Schrier, D. J.; Dyer, R. D. Design of 5-(3,5-Ti-tert-butyl-
4-hydroxyphenyl)-1,3,4-thiadiazoles, -1,3,4-Oxadiazoles, and
-1,2,4-Triazoles as Orally Active, Nonulcerogenic Anti-inflam-
matory Agents. J. Med. Chem. 1993, 36, 1090–1099. (b)
Boschelli, D. H.; Connor, D. T.; Bornemeier, D. A.; Dyer, R. D.;
Kennedy, J. A.; Kuipers, P. J.; Okonkwo, G. C.; Schrier, D. J.;
Wright, C. D. 1,3,4-Oxadiazole, 1,3,4-Thiadiazole, and 1,2,4-
Triazole Analogs of the Fenamates: In Vitro Inhibition of
3
9.50 ppm for 13 C NMR). Melting point was determined
using X-4 made by Peking Taike Apparatus Co. Ltd. High
resolution mass spectra (HRMS) were measured with a
Waters Micromass GCT instrument.
1
General procedure for one-pot synthesis for 3,5-
disubstituted 1,2,4-thiadiazoles
Chandrakantha, B.; Isloor, A. M.; Shetty, P.; Fun, H. K.;
Hedgde, G. Synthesis of Oleanolic Acid Derivatives: In Vitro,
In an oven-dried undivided three-necked bottle (25 mL)
equipped with a stir bar, amidine or guanidines hydrochlor-
ide 1 (0.3 mmol), isothiocyanate 2 (0.33 mmol), NEt3
036. (d) Chapleo, C. B.; Myers, M.; Myers, P. L.; Saville, J. F.;
Smith, A. C. B.; Stillings, M. R.; Tulloch, I. F.; Walter, D. S.;
Welbourn, A. P. Substituted 1,3,4-Thiadiazoles with
(
0.6 mmol), and CH CN (6 mL) were added and stirred at
3
room temperature until the reaction was complete. The
resulting imidoyl thiourea 3 was obtained without isolation.
Subsequently, the three-necked bottle was equipped with
graphite rod (6 / mm, about 15 mm immersion depth in
solution) as the anode and platinum plate (15 mm ꢀ 15 mm
[
2] (a) Chen, L.; Zhu, Y. J.; Fan, Z. J.; Guo, X. F.; Zhang, Z. M.;
Xu, J. H.; Song, Y. Q.; Yurievich, M. Y.; Belskaya, N. P.;
Bakulev, V. A. Synthesis of 1,2,3-Thiadiazole and Thiazole-
ꢀ
0.3 mm) as the cathode, n-Bu NI (0.3 mmol, 0.05 M) was
4
(
b) Chen, L.; Guo, X. F.; Fan, Z. J.; Zhang, N. L.; Zhu, Y. J.;
added. Then the electrolysis system was stirred at a constant
current of 20 mA at room temperature for 3 h. When the
reaction finished, the reaction mixture was washed with
water and extracted with ethyl acetate (10 mL x 3). The
organic layers were combined, dried over Na SO . The solv-
Zhang, Z. M.; Khazhieva, I.; Yurievich, M. Y.; Belskaya, N. P.;
Bakulev, V. A. Synthesis and Fungicidal Activity of 3,4-
Dichloroisothiazole Based Strobilurins as Potent Fungicide
2
4
[
3] (a) Fusco, S.; Centore, R.; Riccio, P.; Quatela, A.; Stracci, G.;
Archetti, G.; Kuball, H. G. NLO-active Polymers Containing
Triazolo-thiadiazole Segments. Polymer 2008, 49, 186–191. (b)
Courtel, F. M.; Hammami, A.; Imbeault, R.; Hersant, G.;
Paynter, R. W.; Marsan, B.; Morin, M. Synthesis of n-Type
ent was removed under reduced pressure, and the crude
product was purified by column chromatography on silica
gel to give pure products 4 and 5. The Supplemental
Materials contains full characterization for products 4 and 5