Molecular Diversity https://doi.org/10.1007/s11030-018-9814-7 SHORT COMMUNICATION Microwave-assisted green synthesis of 4,5-dihydro-1H -pyrazole-1-carbothioamides in water Hamid Reza Farmani 1 · Mohammad Hossein Mosslemin 1 · Bahareh Sadeghi 1 Received: 23 April 2017 / Accepted: 27 February 2018 © Springer International Publishing AG, part of Springer Nature 2018 Abstract Rapid, efficient, simple and green procedure for the synthesis of 4,5-dihydro-1 H -pyrazole-1-carbothioamides via the multi- component reaction of aryl aldehydes, acetophenones and thiosemicarbazide in water in the presence of tetrabutylammonium hydroxide under microwave irradiation is reported. Keywords 4,5-Dihydro-1 H -pyrazole-1-carbothioamides · Microwave irradiation · Multicomponent reaction · Green chemistry · Water · TBAOH · MCRs Introduction The booming field of diversity-oriented synthesis (DOS) has been exploited to generate novel and highly functionalized small molecule libraries. The development of environmen- tally sound, green and economic synthetic procedures is of utmost interest. Among key criteria for green chemistry, the design of energy-efficient processes and the use of safer sol- vents are highly sought [1,2]. Microwave-assisted organic synthesis (MAOS) enables chemists save time and prepare products in almost quanti- tative yields and with high selectivity. Thus, this technology is now being used widely as an alternative to conventional heating in many reaction types [3,4]. MAOS in combination with multicomponent synthesis aligns with the principles of green chemistry that include atom economy, facile execution, ease of diversification and high reaction efficiency [5,6]. Organic synthesis in aqueous media is of high interest due to the unique properties of water such as immense heat capac- ity, high dielectric constant, large temperature window, low cost and eco-compatibility [7–9]. In this regard, the develop- Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-018-9814-7) contains supplementary material, which is available to authorized users. B Hamid Reza Farmani Hrfarmani@iauyazd.ac.ir 1 Department of Chemistry, Yazd Branch, Islamic Azad University, P.O. Box 89195-155, Yazd, Iran ment of green protocols in water under microwave irradiation is highly desirable. As bioactive molecular frameworks, pyrazoles can serve as lead compounds for the development of new pharma- ceuticals [10]. In particular, 4,5-dihydro-1 H -pyrazole-1- carbothioamides (DPCs) are established as potent thera- peutics for several CNS diseases such as Parkinson’s and Alzheimer’s by selective inhibition against both isoforms of monoamine oxidase (MAO) (Fig. 1)[11]. Furthermore, this privileged scaffold stands out as an effective antidepressant [12]. In addition, this type of compounds has been described with superior anticancer activity against the MCF-7 (human breast) [13], HeLa (human cervix) [14], 5647 and T24 (human bladder) [15] carcinoma cell lines. Other biolog- ical evaluations revealed that 4,5-dihydro-1 H -pyrazole-1- carbothioamide derivatives demonstrate promising antimi- crobial [16], antiviral [17], anti-inflammatory [18], antitu- bercular [19] and anti-amebic [20] behaviors. Encouraged by these pharmacological and biological properties, we envis- aged to develop a green procedure for the synthesis of thiocarbamoyl pyrazolines. A well-established strategy the synthesis of DPCs usually adopts the condensation of chal- cones with thiosemicarbazide in the presence of sodium or potassium hydroxide [21]. Another route involves the reaction of 3,5-diaryl-4,5-dihydro-1 H -pyrazoles and isoth- iocyanate derivatives [22]. In contrast to the many multistep processes reported for the syntheses of DPCs, these method- ologies pose a series of challenges such as low yields (48–58%), limited substrate scopes, long reaction times and 123