Vol.:(0123456789) 1 3 Molecular Diversity https://doi.org/10.1007/s11030-019-09981-0 ORIGINAL ARTICLE A synthesis of N‑(1H‑pyrazol‑5‑yl)‑1,3,4‑thiadiazol‑2(3H)‑imines from nitrile imines and Erlenmeyer thioazlactones Issa Yavari 1  · Zohreh Taheri 1  · Sara Sheikhi 1  · Samira Bahemmat 2  · Mohammad R. Halvagar 2 Received: 7 June 2019 / Accepted: 17 July 2019 © Springer Nature Switzerland AG 2019 Abstract Erlenmeyer thioazlactones are reacted with hydrazonoyl chlorides in the presence of Et 3 N to aford functionalized N-(1H- pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines in excellent yields. This strategy is based on a domino double 1,3-dipolar cycloaddition reaction of nitrile imines to Erlenmeyer thioazlactones, followed by the elimination of carbon monoxide and phenylmethanthiol from the initially formed cycloadducts. This method provides fast access to a variety of structurally diverse N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines. The structure of a typical product was established by X-ray crystallography. Graphic abstract Keywords Pyrazoles · 2-Amino-1,3,4-thiadiazole · Nitrile imines · 1,3-Dipolar cycloaddition · Arylidenethioazlactones Introduction The combination of two or more distinct bioactive sub-uni- ties in one frame, well documented as molecular hybridiza- tion, is an emerging approach in the design of new drugs [1, 2]. Pyrazoles represent an important structural subunit in natural products and drug molecules. Due to their unique pharmacological properties and biological activities, they occupy an important position in heterocyclic chemistry [3–5]. Many small-molecule drugs contain the pyrazole moiety [6–8]. Currently, pyrazoles are employed as key constituents of ligands for transition metals [9], receptors in supramolecular chemistry [10], liquid crystals [11] and polymers [12]. 1,3,4-Thiadiazole is a unique template that is associ- ated with several biological activities [13]. 2-Amino-1,3,4- thiadiazole occupies an important place in pharmaceutical chemistry [14]. Some of the best-known drugs based on 2-amino-1,3,4-thiadiazole are acetazolamide, methazola- mide, and megazol [15]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-019-09981-0) contains supplementary material, which is available to authorized users. * Issa Yavari yavarisa@modares.ac.ir 1 Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran 2 Department of Inorganic Chemistry, Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran