Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

Abstract

The efficient syntheses of various metallocenyl thioamides using a single-step three-component condensation reaction between the commercially available (dimethylaminomethyl)ferrocene or aminomethylferrocene and another organic amine in the presence of elemental sulfur are described. All new organometallic thioamide derivatives were unambiguously characterized by 1 H and 13 C NMR spectroscopy and mass spectrometry. Furthermore, the structures of five ferrocenyl thioamides determined by X-ray crystallography are presented. ■ INTRODUCTIONThioamide is an important and useful functional group in chemistry as well as in biology. Thioamides are not only present in medicinally important molecules but are also used as building blocks for the construction of pharmacologically important molecules containing nitrogen and sulfur heterocycles, 1−4 which ultimately find uses as potent antitumor agents and enzyme inhibitors. 1,5−7 Very recently, the thioamide functionality was utilized as a fluorescent quencher in probes designed to monitor protein folding, function, and protein− protein interactions. 8−10 Additionally, thioamide-functionalized fluorescent dyes were successfully employed as sensors for metal ions. 11−13 The principles of such sensors rely on the selective desulfurization of thioamides by thiophilic metal ions. For example, Chang et al. reported a thioamide−pyrene conjugate for the selective detection of Zr 4+ ion in solution. 12 In the presence of Zr 4+ and H 2 O 2 , the thioamide−pyrene conjugate is desulfurized and generates the corresponding amide−pyrene conjugate. This leads to a switch in fluorescence and hence to a selective detection of the Zr 4+ ion.Since its serendipitous discovery in the 1950s, 14 ferrocene has gained the attention of organic as well as inorganic chemists due to its very unique structure, stability, and attractive electrochemical properties. 15 These characteristics have been employed for catalysis purposes, 16 in material science, 17−19 for biosensing applications, 20,21 and more recently in the field of bioorganometallic chemistry. 22−30 Ferrocene derivatives containing a thioamide functionality directly attached to the cyclopentadienyl ring were shown to be very good auxiliary substituents for the generation of cyclopalladated ferrocene derivatives 31,32 as well as being useful as precursors for the synthesis of various ligands used in asymmetric organic synthesis 33,34 and for the electrochemical detection of anions. 35 Despite this importance, to our surprise, there have been only a few reports in the literature describing the synthesis of ferrocenyl thioamides and, more generally, of organometalliccontaining thioamide derivatives. The reason is most likely related to synthetic difficulties, since, in comparison to purely organic compounds, organometallic complexes are sometimes more sensitive toward certain reagents and reaction conditions.To date, the typical and general routes to prepare ferrocenyl thioamides are the thionation of ferrocenyl amides 35,36 (route A, Scheme 1) or ...

Crystal structure of a new phenyl(morpholino)methanethione derivative: 4-[(morpholin-4-yl)carbothioyl]benzoic acid

“…morpholin-4-yl(phenyl)methanethione (Guntreddi et al, 2014;Chen et al, 2016). Similar structures with a planar nucleus and a chair conformation around the methanethione group have also been reported, including 1-(4-chlorothiobenzoyl)piperidine (Muthuraj et al, 2007), piperidin-1-yl(pyridin-4-yl)methanethione (Ray et al, 2013), ferrocen-1-yl(morpholin-4-yl)methanethione (Patra et al, 2013) and (3,5-dimethyl-1Hpyrazo-1-yl)(morpholin-4-yl)methanethione (El-Sayed et al, 2018).…”

Sedaxicenes: potential new antifungal ferrocene-based agents?

“…The synthesis of the metallocenyl analogues of sedaxane, that we have named sedaxicenes, was performed according to the established protocols (see Scheme 2). 16 The products 1a, 1b, 2 and 3 were all obtained in moderate yields (23-58%). The new complexes were characterized by 1 H, 13 C and 19 F NMR spectroscopy as well as ESI-MS and X-ray diffraction studies, and their purity was assessed by elemental analysis (<0.5% from the calculated value).…”

Recent Advances in Organic Reactions Involving Elemental Sulfur

“…The strategy of using two different amines was successfully applied in the efficient syntheses of various metallocenyl thioamides 446 . This synthesis consisted in a one‐step reaction using commercially available methylamines 444 bearing a ferrocene or ruthenocene moiety with another organic amine in the presence of elemental sulfur (Scheme ) …”