Aromatic bis-urea derivates: synthesis, protonation properties and anion complexation

Abstract

Sintetizirano je osam bis-ureidnih derivata orto- i meta-fenilendiamina koji se razlikuju po supstituentima na ureidnim podjedinicama vezanim na središnji benzenski prsten koji služi kao premosnica. Pri tome su uvedeni različiti supstituenti (-CH3, -OCH3 i -NO2) u para-položaj perifernih benzenskih prstena. Strukturne promjene uvedene su s ciljem istraživanja utjecaja geometrijske komplementarnosti struktura receptora s anionskim vrstama na stabilnost odgovarajućih kompleksa u otopini. Također je promatran i utjecaj steričkih te induktivnih efekata supstituenata na ravnoteže reakcija proučavanih u okviru ovog rada. Detaljno su istražene reakcije receptora s acetatom i dihidrogenfosfatom u dimetil-sulfoksidu te je utvrđeno da u otopinama soli navedenih aniona i ispitivanih liganada dolazi do uspostave složenog sustava kemijskih ravnoteža. Iscrpnim istraživanjem ustanovljeno je da uz reakcije nastajanja kompleksa anion-receptor dolazi i do disocijacije liganada uslijed protonacije i homokonjugacije aniona. Korištenjem brojnih fizikalno-kemijskih metoda (spektroskopija 1H NMR, spektrofotometrija, konduktometrija, mikrokalorimetrija) provedena je termodinamička karakterizacija svih navedenih reakcija. Kompeticijskim spektrofotometrijskim titracijama određene su konstante ravnoteže protonacije acetata i dihidrogenfosfata u dimetil-sulfoksidu, a reakcije homokonjugacije dodatno su istražene konduktometrijski i mikrokalorimetrijski te su izmjerene odgovarajuće reakcijske entalpije i entropije. Rezultati dobiveni u slučaju acetata u dobrom su slaganju s literaturnim vrijednostima, dok su vrijednosti konstanti ravnoteže protonacije i homokonjugacije dihidrogenfosfata u dimetil-sulfoksidu određene po prvi puta. Protonacijska svojstva bis-ureidnih liganada istražena su 1H NMR te spektrofotometrijskim titracijama s 1,8-diazabiciklo[5.4.0]undek-7-enom. Utvrđeno je da dolazi do disocijacije obje ureidne skupine te su određene odgovarajuće konstante ravnoteže. Stvaranje anionskih kompleksa kvantitativno je istraženo spektrofotometrijski i spektroskopijom 1H NMR, na temelju čega se stekao i uvid u osnovne strukturne karakteristike kompleksa. Utvrđeno je da nastaju stabilni anionski kompleksi stehiometrije 1:1 i 2:1 (anion:receptor), što je dodatno potvrđeno konduktometrijski. Također je ustanovljeno da su stabilnosti kompleksa s acetatom i dihidrogenfosfatom slične u slučaju orto-bis-ureidnih receptora, dok je kod meta-bis-ureidnih receptora uočeno povoljnije kompleksiranje dihidrogenfosfata. Važno je napomenuti da su prilikom obrade podataka u odgovarajuće modele uključene i reakcije prijenosa protona. Premda je značaj tih reakcija u otopinama i ranije prepoznat, one su u ovom radu po prvi puta kvantitativno uzete u obzir. Također, primijećeno je da bazičnost aniona nije jedini niti presudan faktor kojim su određene termodinamičke stabilnosti anionskih kompleksa s istraženim ligandima. Znatan utjecaj na stabilnost ima komplementarnost geometrije veznog mjesta receptora s geometrijom anionskih vrsta u otopini, kao i mogućnost nastajanja intramolekulskih vodikovih veza. Opaženi utjecaj supstituenata na perifernim benzenskih prstenima na proučavane reakcije može se pripisati njihovim elektron-donorskim odnosno elektron-akceptorskim značajkama što utječe na kiselost ureidnih skupina odnosno njihov afinitet za stvaranje vodikovih veza.Eight ortho- and meta-phenylenediamine bis-urea derivatives, which differ in substituents in the urea moieties connected to the central benzene ring, were synthesised. Different substituents (-CH3, -OCH3, -NO2) were introduced in the peripheral phenyl groups of the studied compounds. The structural changes were implemented to study the influence of the geometrical complementarity of the receptor structures with that of the anions on the stability of the corresponding complexes in solution. Sterical and inductive influences of the substituents on the equilibria of the studied processes were investigated as well. Reactions with acetate and dihydrogen phosphate in dimethyl sulfoxide were studied thoroughly and it was determined that in the solutions containing anions and the studied ligands a complex chemical equilibrium system was established. A detailed study indicated that besides complex formation deprotonation of the ligands coupled with protonation and homoconjugation of the basic anions occurred. The use of several physico-chemical methods (1H NMR spectroscopy, spectrophotometry, microcalorimetry, conductometry) enabled quantitative characterisation of all the investigated reactions. The equilibrium constants of protonation and homoconjugation of acetate and dihydrogen phosphate in dimethyl sulfoxide were determined by competitive spectrophotometric titrations. The homoconjugation reactions were additionally studied by conductometry and microcalorimetry, which enabled their thorough thermodynamic characterisation, i.e. determination of the corresponding reaction enthalpies and entropies. The results obtained in the case of acetate were in good agreement with the previously published data, whereas the analogous results regarding dihydrogen phosphate are reported for the first time in this work. Protonation properties of the bis-urea ligands were investigated by means of spectrophotometric and 1H NMR titrations with 1,8-diazabicyclo[5.4.0]undec-7-ene. It was found that dissociation of both urea moieties took place and the related equilibrium constants were determined. Formation of anion complexes was studied by UV and 1H NMR spectrometries which enabled insight into the structural characteristics of the investigated complexes. The formation of stable complexes of 1:1 and 2:1 (anion:receptor) stoichiometries was detected, and was additionally confirmed by conductometric measurements. Stabilities of the complexes with dihydrogen phosphate and acetate were similar in the case of ortho-bis-urea receptors whereas meta-bis-urea receptors were found to preferably bind dihydrogen phosphate. It should be noted that proton-transfer reactions were taken into account in the interpretation of the experimental data. Although the importance of these reactions in dimethylsulfoxide was often recognised in the literature, in this work they were for the first time taken into account quantitatively. Additionally, it was observed that basicity of the anions was not the main nor decisive factor by which thermodynamic stabilities of the complexes with the investigated ligands were determined. Complementarity of the receptor and anion geometries, as well as the possibility of formation of intramolecular hydrogen bonds was proven to be of considerable importance in determining the complex stabilities. The observed influence of the substituents on the peripheral phenyl groups on the studied reactions can be ascribed to their electron-donating or electron-withdrawing properties that affect the acidity of urea compounds as well as their affinity for the formation of hydrogen bonds