Mild and convenient one-pot synthesis of 2-amino-1,3,4-thiadiazoles using trimethylsilyl isothiocyanate (TMSNCS)

Abstract

A novel and efficient one-pot method has been developed for the synthesis of 2-amino-1,3,4-thiadiazoles using various carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS). In situ preparation of various thiosemicarbazides by the reaction of different carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS), followed by cyclodehydration of thiosemicarbazides under acidic conditions gave 2-amino-1,3,4-thiadiazoles in high yields (71-87%).

I2 Promoted Synthesis of 2‐Aminothiadiazoles Employing KSCN as a Sulfur Source Under Metal‐Free Conditions

“…5‐Phenyl‐1,3,4‐thiadiazol‐2‐amine (4a): Yield: 83 % ; Colorless solid, m.p. 213–214 °C; 1 H NMR (400 MHz, [D 6 ]DMSO) δ = 7.71 (d, J = 6.9 Hz, 2H), 7.41 (m, 5H).…”

“…5‐(Thiophen‐2‐yl)‐1,3,4‐thiadiazol‐2‐amine (4n): Yield: 64 %; brown solid, m.p. 205–207 °C; 1 H NMR (400 MHz, [D 6 ]DMSO) δ = 7.58 (d, J = 5.0 Hz, 1H), 7.42 (br s, 2H), 7.37 (d, J = 2.8 Hz, 1H), 7.10–7.06 (m, 1H).…”

“…These methods usually require the use of pre‐prepared substrates that was prepared from aldehydes and the corresponding hydrazine/urea/semicarbazide/thioure. In some cyclization reports, hydrazide and isothiocyanate, dithiocarbamates or trimethylsilyl isothiocyanate(TMSNCS) were used to prepare 2‐amino‐1,3,4‐thiadiazoles as starting material with several different reagents such as p ‐TsCl/TEA, POCl 3 trimethylamine or H 2 SO 4 . Nevertheless, these reported strategies generally require the use of unstable, moisture sensitive, expensive, or hazardous materials, and harsh reaction conditions.…”

Acid Hydrazides

“…The method involves in situ generation of thiosemicarbazides, which undergo acid-catalyzed cyclodehydration to give 2-amino-5-aryl-1,3,4-thiadiazoles. 9 DMF, 60 °C (D) Guo, Fan, and co-workers have reported a highly regioselective synthesis of 1-acyl-5-hydroxypyrazolines through the condensation of 1,2-allenic ketones. These were further transformed into 1-acyl pyrazoles.…”

One-pot synthesis of 5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one derivatives

“…Compounds 2a-o were synthesized by the method reported in the literature. 18,[22][23][24][25][26][27][28][29][30][31][32] The mechanism of the synthesis is shown in Scheme 3.…”