Reactivity of ferrocenylalkylazoles under conditions of dissociative ionization

Abstract

Electron ionization mass spectra of biologically active ferrocenylalkylazoles CpFeC 5 H 4 CH(R)Az (R = H, Me, Et, Pr, or Ph; AzH is pyrazole, imidazole, indazole, benzoimidazole, benzotriazole, adenine, or their derivatives) were studied. The nature of the heterocyclic fragment (its ionization energy) is the main factor determining the reactivity of these compounds under conditions of dissociative electron ionization.Pronounced antitumor activity of ferrocenylalkylazoles combined with low toxicity allows these compounds to be considered as precursors for the design of highly efficient drugs for chemotherapy of tumor diseases. 1-4 In this con nection, studies of the physicochemical properties and reactivities of these compounds are of considerable im portance. In the present study, we examined the behavior of ferrocenylalkylazoles 1-23 with the composition CpFeC 5 H 4 CH(R)Az (R = H, Me, Et, Pr, or Ph; AzH is pyrazole, imidazole, indazole, benzoimidazole, benzo triazole, adenine, or their derivatives) under conditions of dissociative electron ionization (Scheme 1) by mass spectrometry. Our interest here is with both the analytical and research aspects of this problem. The former consists of the development of procedures for the determination of the compositions, structures, and purities of this class of biologically active compounds. The latter consists of the study of the reactivities of such molecules and their ions in the gas phase. Results and DiscussionThe mass spectra of all the compounds under study have intense peaks of molecular ions, whose fragmenta tion follows several paths. The ordinary cleavage of the metal-ligand bond with elimination of substituted and unsubstituted cyclopentadienyl ligands up to the forma tion of the free iron cation 5,6 is common to these com pounds, as well as to all ferrocene derivatives.The characteristic feature of the behavior of all ferrocenylalkylazoles under conditions of dissociative electron ionization is that they undergo a rearrangement accompanied by migration of the heterocyclic fragment Scheme 1 R = H (1-9), Me (10-17), Et (18-20), Pr (21, 22), Ph (23)to the iron atom giving rise to the CpFeAz + and FeAz + ions containing the metal-azole bond (see Scheme 1).

The nature of ferrocenylalkylating agent in the acid-catalyzed reactions with ferrocenyl(phenyl)methanol

“…A characteristic feature of all ferrocenyl(alkyl)azole is the rearrangement with the migration of the heterocyclic moiety to the iron atom, resulting in the formation of the [CpFeNu] + ions with a 5-79% abundance, which contain a metal-azole bond. 40 This process occurs in most ferrocenylalkyl derivatives CpFeC 5 H 4 CHRX containing a nucleophilic moiety X = OH, NR 2 , halogen, etc. 39,41 In our case, the main fragmentation pathway is elimination of the heterocycle with the heterolytic cleavage of the C-N bond and the formation of a fragment ion [MCHPh] + (m/z 275) and ions Nu + .…”

The reactivity of ferrocenylalkyl azoles under the conditions of electrospray ionization

“…Thus, the oxidation of the initial molecule by its protonated form [M+H] + and(or) by ferrocenylalkyl cation is the most energetically beneficial process for the formation of the molecular ions of ferrocenylalkyl derivatives under the ESI conditions. From the three possible ways of formation of ferrocenylalkyl cation, namely: fragmentation of molecular ion with the elimination of azole radical, as it takes place under the conditions of ionization by electrons [14] (reaction 5), heterolytic decomposition of a neutral molecule with the elimination of the azolyl anion (reaction 6) and protonation with the following release of an azole molecule (sequence reactions 1 and 7) the last process is the most energetically beneficial with DH from À29.99 to À34.76 kcal/mol. Hence, the ferrocenylalkyl cation only formally can be assigned to the products of the molecular ion fragmentation, while in fact it is formed through the stage of protonation of the initial molecule.…”