Synthesis of ferrocenyl pyrazoles by the reaction of 3-ferrocenylpropynal with hydrazinium salts Metin Zora a, * , Ays ße Nur Pinar a , Mustafa Odabas ßog˘lu b,1 , Orhan Bu¨yu¨kgu¨ngo¨r c,1 , Gu¨ nseli Turgut d a Department of Chemistry, Faculty of Arts and Sciences, Middle East Technical University, 06531 Ankara, Turkey b Department of Chemistry, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Kurupelit Samsun, Turkey c Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Kurupelit Samsun, Turkey d Department of Chemistry, Faculty of Arts and Sciences, Akdeniz University, 07058 Antalya, Turkey Received 23 August 2007; received in revised form 19 October 2007; accepted 19 October 2007 Available online 26 October 2007 Abstract Synthesis of ferrocenyl-substituted pyrazoles via the reaction between 3-ferrocenylpropynal and hydrazinium salts is described. Depending upon the substitution pattern of hydrazine derivative, the reaction affords 1-alkyl/aryl-5-ferrocenylpyrazoles and/or 1- alkyl/aryl-3-ferrocenylpyrazoles. Structures of 5-ferrocenyl-1-phenyl-1H-pyrazole, 1-benzyl-5-ferrocenyl-1H-pyrazole and 2-(3-ferro- cenylpyrazol-1-yl)ethanol were identified by X-ray crystallography. Ó 2007 Elsevier B.V. All rights reserved. Keywords: Ferrocene; Pyrazole; Hydrazine; Propynal; Cyclization; Condensation 1. Introduction The rapid spread of cancer has sparked an intense chem- ical search for new structure leads which may be of use in designing novel antitumor drugs. In this regard, pyrazoles have been the focus of a large number of investigations in the design and synthesis of novel biologically active agents that show remarkable anticancer activities [1]. Pyra- zoles have been studied for over a century as an important class of heterocyclic compounds and still continue to attract considerable attention due to the wide range of medicinal activities they possess, such as analgesic, antimi- crobial, antiviral, anti-inflammatory, hypoglycemic, anti- hypertensive and antitumor properties [1,2]. Recent studies have shown that substitution of an aromatic nucleus of such structures with a ferrocene unit can lead to products with enhanced or unexpected biological activity which is absent or less manifest in the parent molecule [3,4]. Owing to its unique structure, different membrane-permeation behavior and anomalous metabolism, ferrocene is often integrated into a compound in order to obtain unexpected or enhanced biological activities [3,4]. Thus, in recent years, substantial effort has been devoted to the synthesis of new ferrocene derivatives since the properly functionalized derivatives could be potential antitumor substances [5,6]. Although pyrazoles are among the most intensely studied compounds [7–9], ferrocenyl-substituted derivatives are rel- atively less explored [10,11]. In this regard, the reactions of acetylenic ketones (alkynones) with hydrazines have been frequently used to synthesize pyrazole derivatives [8,9]. However, analogous reactions between acetylenic alde- hydes (alkynals) and hydrazines are almost unknown since, to the best of our knowledge, there is only one example of such reaction [9]. It has been reported that the microwave- assisted reaction of 3-phenylpropynal with phenylhydr- azine provided 1,3- and 1,5-diphenylpyrazoles in 58% and 28% yields, respectively [9]. As a part of our general 0022-328X/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jorganchem.2007.10.035 * Corresponding author. Tel.: +90 312 2103213; fax: +90 312 2103200. E-mail address: zora@metu.edu.tr (M. Zora). 1 Authors to whom inquiries concerning the X-ray analysis should be directed. www.elsevier.com/locate/jorganchem Available online at www.sciencedirect.com Journal of Organometallic Chemistry 693 (2008) 145–154