Sinteza novih biološki aktivnih heterocikličnih jedinjenja koja sadrže ferocen

Abstract

U ovom radu opisana je sinteza i spektroskopska karakterizacija heterocikličnih jedinjenja koja sadrže ferocenil-grupu, a predstavljaju derivate jednog od sledećih pet hetorocikla:- 1,3-tiazolidin-4-on,- 2,3-dihidrohinolin-4(1H)-on,- 1,3-oksazinan,- 1,3-oksazinan-2-on I - tetrahidropirimidin-2(1N)-on. Sinteza prve grupe heterocikličnih jedinjenja - derivata tiazolidinona koji u položaju 2 sadrže ferocenil-grupu, 92a-l, ostvarena je polazeći od trgovački dostupnih supstrata – tioglikolne kiseline, ferocenaldehida (90) i odgovarajućih amina (91a-l). Ova trokomponentna reakcija odvija se u jednoj fazi (one pot reakcija), izlaganjem smese reaktanata ultrazvučnim talasima u prisustvu N,N'-dicikloheksil-karbodiimida (DCC) kao dehidratacionog sredstva. Nađeno je da se najviši prinosi (48-99%) ostvaruju kada je odnos reaktana 0/91a-l/tioglikolnakiselina = 1:1:2. Sva jedinjenja (koja su sintetisana po prvi put) izolovana su u čistom stanju i detaljno okarakterisana fizičkim i spektroskopskim podacima (tačke topljenja, mikroanaliza, IR, 1H i 13C NMR, MS i HRMS), a jedno od njih (92j) bilo je podesno za rendgenostrukturnu kristalnu analizu, pa mu je na taj način nedvosmisleno potvrđena struktura. Redoks osobine svih trinaest tiazolidinona ispitane su elektrohemijski, tehnikom ciklične voltametrije i nađeno je da u opsegu potencijala 0,000-1,000 V jedinu elektroforu u njihovoj strukturi predstavlja ferocensko jezgro. Redoks potencijali ovih jedinjenja (E1/2 = 0,487-0,512V) nešto su pozitivniji od redoks potencijala ferocena (0,391 V), što se objašnjava činjenicom da je ferocensko jezgro vezano za ugljenikov atom koji nosi dva heteroatoma.

In this work, the synthesis and spectral characterization of a variety of novel ferrocene derivatives containing one of the following five heterocyclic scaffolds has been described: - 1,3-thiazolidin-4-one, - 2,3-dihydroquinolin-4(1H)-one, - 1,3-oxazinane,- 1,3-oxazinan-2-one,- tetrahydropyrimidin-2-one. The synthesis of the first group of heterocyclic compounds – derivatives of thiazolidinone bearing a ferrocenyl group at position 2, 92а-л, – was performed using the commercially available substrates thioglycolic acid, ferrocenecarboxaldehyde (90) and the appropriate amines 91а-л. This three-component reaction was carried out in one step (onepot reaction) through ultrasonic irradiation of the mixture of reactants and N,N'-dicyclohexylcarbodiimide (DCC) as the dehydrating agent. It was found that the highest yields (48-99%) were achieved with a 90/91а-л/thioglycolic acid = 1:1:2 ratio. All new products (synthesized for the first time) were isolated in pure form and characterized in detail by means of their physical and spectral data (melting points, microanalysis, IR, 1H and 13C NMR, MS and HRMS). One of them (92j) was found to be suitable for single-crystal X-ray diffraction analysis, thus providing unambiguous confirmation for its molecular structure. Redox properties of all thirteen thiazolidinone derivatives were assessed by an electrochemical technique (cyclic voltammetry), and it was found that the ferrocene unit represents the only electrophore present in these structures in the potential window 0.000-1.000 V. The redox potentials of these compounds (E1/2 = 0.487- 0.512 V) were slightly more positive than that of ferrocene itself (0.391 V), and this is a consequence of the fact that the ferrocene unit is connected to a carbon atom bearing two electronegative heteroatoms.