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

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

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

The direct and selective mechanochemical halogenation of C–H bonds in unsymmetrically substituted azobenzenes using N-halosuccinimides as the halogen source under neat grinding or liquid-assisted grinding conditions in a ball mill has been described. Depending on the azobenzene substrate used, halogenation of the C–H bonds occurs in the absence or only in the presence of PdII catalysts. Insight into the reaction dynamics and characterization of the products was achieved by in situ Raman and ex situ NMR spectroscopy and PXRD analysis. A strong influence of the different 4, 4’-substituents of azobenzene on the halogenation time and mechanism was found

Solid-State Supramolecular Assembly of Salicylic Acid and 2-Pyridone, 3-Hydroxypyridine or 4-Pyridone

Mechanochemical milling of equimolar mixtures of salicylic acid with three hydroxy derivatives of pyridine provided three new phases. With 2-hydroxypyridine, which is in fact present as 2-pyridone, a discrete cocrystal supramolecular assembly is formed. 3-hydroxypyridine and salicylic acid formed a salt and an extended network of hydrogen bonds while the product of the reaction of 4-hydroxypyridine (present as 4-pyridone) and salicylic acid remained structurally uncharacterized. All three hydroxypyridines retain the tautomeric form as in their respective pure phases upon cocrystal formation. Where possible, reaction profiles have been extracted from in situ monitoring via Rietveld refinement to show direct product formation which could be well described using the first-order reaction rate law. This work is licensed under a Creative Commons Attribution 4.0 International License

Isotope Labeling Reveals Fast Atomic and Molecular Exchange in Mechanochemical Milling Reactions

Using tandem in situ monitoring and isotope-labeled solids, we reveal that mechanochemical ball-milling overcomes inherently slow solid-state diffusion through continuous comminution and growth of milled particles. This process occurs with or without a net chemical reaction and also occurs between solids and liquid additives that can be practically used for highly efficient deuterium labeling of solids. The presented findings reveal a fundamental aspect of milling reactions and also delineate a methodology that should be considered in the study of mechanochemical reaction mechanisms

Palladium-mediated ligand-directed C–H bond activation and halogenation by mechanochemistry

Izravno i selektivno uvođenje funkcionalnih skupina postignuto zamjenom inertnih veza C–H jedan je od sintetskih koraka u pripremi brojnih organskih spojeva. Ove kemijske transformacije još uvijek se pretežno oslanjaju na protokole koji uključuju upotrebu otapala, koji su često dugotrajni, zahtijevaju topljive reaktante i korištenje otrovnih otapala. U ovom su radu, kao njihova ekološki prihvatljivija alternativa, razvijeni protokoli u čvrstom stanju za aktivaciju veze C–H i halogeniranje usmjereno ligandom i katalizirano paladijevim(II) spojevima. Za ove transformacije odabrani su supstrati s donorskom skupinom koja se veže na metalni centar i dovodi ga u blizinu specifične veze C–H. Aktivacijom veze C–H nastaje reaktivna veza C–Pd koja se nakon reakcije s N-halogensukcinimidom transformira u željenu vezu C–X. Praćenjem reakcija in situ i/ili ex situ metodama te izolacijom i karakterizacijom produkata i međuprodukata pružen je uvid u mehanizam aktivacije i halogeniranja veze C–H u čvrstom stanju i otkriven snažan učinak krutih i tekućih aditiva na prirodu i reaktivnost katalitički aktivnih vrsta Pd(II) i međuprodukata.Direct and selective introduction of functional groups achieved by replacement of inert C–H bonds is one of the synthetic steps in the preparation of many organic compounds. These processes still rely heavily on solvent-based protocols, which are often time-consuming and require reactants solubility, and use toxic solvents. In this work, solid-state protocols for palladium-mediated ligand-directed C–H bond activation and halogenation were developed as a more environmentally friendly alternative. Substrates with donor group that binds to the metal center, positioning it near the specific C–H bond, were selected for these transformations. A reactive C–Pd bond formed during C–H bond activation transforms into the desired C–X bond upon reaction with N-halosuccinimide. Monitoring of the reactions by in situ and/or ex situ methods, as well as isolation and characterization of the products and intermediates, provided insight into the mechanism of C–H bond activation and halogenation in the solid-state and revealed a strong effect of the solid and liquid additives on the nature and reactivity of the catalytically active Pd(II) species and intermediates

Palladium-mediated ligand-directed C–H bond activation and halogenation by mechanochemistry

Izravno i selektivno uvođenje funkcionalnih skupina postignuto zamjenom inertnih veza C–H jedan je od sintetskih koraka u pripremi brojnih organskih spojeva. Ove kemijske transformacije još uvijek se pretežno oslanjaju na protokole koji uključuju upotrebu otapala, koji su često dugotrajni, zahtijevaju topljive reaktante i korištenje otrovnih otapala. U ovom su radu, kao njihova ekološki prihvatljivija alternativa, razvijeni protokoli u čvrstom stanju za aktivaciju veze C–H i halogeniranje usmjereno ligandom i katalizirano paladijevim(II) spojevima. Za ove transformacije odabrani su supstrati s donorskom skupinom koja se veže na metalni centar i dovodi ga u blizinu specifične veze C–H. Aktivacijom veze C–H nastaje reaktivna veza C–Pd koja se nakon reakcije s N-halogensukcinimidom transformira u željenu vezu C–X. Praćenjem reakcija in situ i/ili ex situ metodama te izolacijom i karakterizacijom produkata i međuprodukata pružen je uvid u mehanizam aktivacije i halogeniranja veze C–H u čvrstom stanju i otkriven snažan učinak krutih i tekućih aditiva na prirodu i reaktivnost katalitički aktivnih vrsta Pd(II) i međuprodukata.Direct and selective introduction of functional groups achieved by replacement of inert C–H bonds is one of the synthetic steps in the preparation of many organic compounds. These processes still rely heavily on solvent-based protocols, which are often time-consuming and require reactants solubility, and use toxic solvents. In this work, solid-state protocols for palladium-mediated ligand-directed C–H bond activation and halogenation were developed as a more environmentally friendly alternative. Substrates with donor group that binds to the metal center, positioning it near the specific C–H bond, were selected for these transformations. A reactive C–Pd bond formed during C–H bond activation transforms into the desired C–X bond upon reaction with N-halosuccinimide. Monitoring of the reactions by in situ and/or ex situ methods, as well as isolation and characterization of the products and intermediates, provided insight into the mechanism of C–H bond activation and halogenation in the solid-state and revealed a strong effect of the solid and liquid additives on the nature and reactivity of the catalytically active Pd(II) species and intermediates

Database Model for Monitoring Skills Development in the Year Before School Enrolment

U svrhu izrade modela baze podataka za praćenje razvoja vještina u godini pred polazak u osnovnu školu obraćena je pozornost na čimbenike koji utječu na razvoj djeteta predškolske dobi. Područja razvoja motorike, govora, spoznaje, igre, emocionalnog i socijalnog razvoja te razvoja likovnih i glazbenih sposobnosti daju uvid u prisutne promjene u djetetovu funkcioniranju. S obzirom na to da odgajatelji i drugi stručni suradnici tijekom pedagoške godine prate razvoj djece kroz neposredni rad, oni također provode i dokumentirano praćenje razvoja periodično kako bi prilagođavali i unaprjeđivali vlastiti pristup. Relacijske baze podataka danas olakšavaju prikupljanje, pohranjivanje, organiziranje i baratanje u mnogim područjima pa je zato osmišljen model baze podataka sa svrhom primjerenom u sustavu ranog i predškolskog odgoja i obrazovanja. Tablice, upiti, izvješća i obrasci u kojima se prikupljaju podaci daju za rezultat lakše baratanje većom količinom informacija.For the purpose of creating a database model for monitoring the development of skills in the year before starting primary school, attention was paid to the factors that affect the development of a preschool child. Areas of motor development, speech, cognition, play, emotional and social development and development of artistic and musical abilities give insight into the present changes in the child's functioning. Given that educators and other professional associates during the pedagogical year monitor the development of children through direct work, they also carry out documented monitoring of development periodically to adapt and improve their own approach. Relational databases today facilitate the collection, storage, organization and handling in many areas, so a database model has been designed with a purpose appropriate in the system of early and preschool education. Tables, queries, reports, and forms in which data is collected result in easier handling of a larger amount of information