A tandem one-pot aqueous phase synthesis of thiazoles/selenazoles B. Madhav, S. Narayana Murthy, B.S.P. Anil Kumar, K. Ramesh, Y.V.D. Nageswar ⇑ Natural Product Chemistry, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500 007, India article info Article history: Received 5 March 2012 Revised 19 April 2012 Accepted 21 April 2012 Available online 11 May 2012 Keywords: Thiazole Selenazole Phenylacetylenes N-Bromo succinimide Water abstract The first ever tandem one-pot synthetic protocol for the synthesis of thiazoles/selenazoles from alkynes via the formation of 2,2-dibromo-1-phenylethanone is reported. The reaction is catalyzed by b-cyclodex- trin in aqueous medium and resulted in good yields. Ó 2012 Elsevier Ltd. All rights reserved. Thiazoles, selenazoles are the principal core structures present in a variety of natural products and have acquired significance due to a wide variety of medicinal and biological properties associated with them (Fig. 1). 1 Selenazoles have been extensively described as synthetic tools, 2 as well as for their biological signifi- cance. 3 1,3-Selenazoles act as antibiotic and cancerostatic 4 (Fig. 1). 2-Amino-1,3-selenazoles are known for their superoxide anion- scavenging activity. 5 Thiazole skeleton has been associated with numerous biologi- cally active molecules, 6 and its derivatives are useful in the treat- ment of hypertension, 7 schizophrenia, 8 inflammation, 9 allergies, 10 bacterial, 11 and HIV 12 infections. In particular, aminothiazoles act as ligands of estrogen receptors 13 as well as a novel class of aden- osine receptor antagonists 14 whereas other analogs are used as fungicides, inhibiting in vivo growth of Xanthomonas and as an ingredient of herbicides and anthelmintic drugs. 15 A few reports have appeared on the synthesis of selenazoles and thiazoles, which include both solid phase synthesis 16 and solution phase 17 synthesis. Narender et al., reported the synthesis of selenazoles/thiazoles by the condensation of phenacylbromides/ tosylates with selenourea/thiourea/thiobenzamide by employing b-cyclodextrin as catalyst. 18 Recently Varma and co-workers synthesized diaryl thiazoles from various a-tosyloxy ketones in water. 19 Several protocols are also described using promoters or catalysts in different organic solvents for the synthesis of thiazoles and selenazoles. However, development of novel environmentally benign approaches for the synthesis of selenazoles/thiazoles, is highly desirable. In continuation of our efforts toward the development of novel ecofriendly methodologies 20 which include the synthesis of het- erocyclic compounds, we report herein, a mild and efficient one- pot protocol for the synthesis of substituted thiazole/selenazole derivatives, for the first time by a three-component reaction, involving phenyl acetylene, N-bromo succinimide and thiourea/ selenourea in aqueous medium (Schemes 1 and 2). To the best of our knowledge there are no reports on the synthesis of thiazoles/ selenazoles from phenylacetylenes. Developing new synthetic ap- proaches in aqueous phase has gained prominence in organic syn- thesis, as it overcomes the harmful effects of organic solvents and reduces the environmental pollution. Water is also economically viable, nontoxic, and the most readily available reaction medium, making it an environmentally acceptable solvent for the design and development of green chemistry protocols. Initialy, phenyl acetylene (1.0 mmol) was reacted with N-bromo succinimide (1.0 mmol) and thiourea (1.0 mmol) in the presence of 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.04.097 ⇑ Corresponding author. Fax: +91 40 27160512. E-mail address: dryvdnageswar@gmail.com (Y.V.D. Nageswar). N S F 3 CO NH 2 H 2 N S N H N S O O O HO OH HO Se N O H 2 N Sulfathiazole (antibacteria)l Riluzole (anticonvulsant) Selenazofurin (antibacterial) Figure 1. Biologically active thiazoles/selenazoles. Tetrahedron Letters 53 (2012) 3835–3838 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet