Pretvorbe dianhidridov biciklo[2.2.2]oktenskih sistemov v N-substituirane derivate s pomočjo nukleofilnih substitucij sukcinanhidridnih fragmentov

Jamšek, Luka (author), Kranjc, Krištof (mentor)

V okviru magistrske naloge sem sintetiziral nove spojine z biciklo[2.2.2]oktenskim skeletom. Z Diels–Alderjevo reakcijo 2H-piran-2-onov z maleinanhidridom sem pripravil dva biciklo[2.2.2]oktena s pripojenima sukcinanhidridnima fragmentoma, ki sem ju uporabil pri nadaljnjih reakcijah derivatizacije. Z reakcijo nukleofilne substitucije s hidrazinom na dianhidridnih obročih in nadaljnjo reakcijo N-substituirane aminske spojine z aromatskimi ali heteroaromatskimi aldehidi sem sintetiziral serijo osemnajstih biciklo[2.2.2]oktenov s pripojenimi hidrazonskimi fragmenti. Za razliko od sintez z aldehidi je reakcija s ketonom potekla slabše, saj je željeni produkt kljub daljšem reakcijskem času nastal le v sledovih. Pripravil sem tudi biciklo[2.2.2]oktene s pripojenimi acilhidrazidnimi fragmenti, vendar produktov ni bilo mogoče izolirati v čisti obliki. Za sintezo teh spojin sem izhodne acilhidrazide pripravil iz analognih etilnih estrov z reakcijo s hidrazin hidratom. Karakterizacijo produktov s pripojenimi acilhidrazidi je ovirala otežena rotacija vezi v DMSO, zaradi katere so bili signali na 1H NMR in 13C NMR spektrih razširjeni. Omenjeno težavo sem poskušal rešiti z merjenjem spektrov pri višji temperaturi ali z uporabo devteriranega topila z manjšo gostoto. Reakcije sinteze obeh tipov produktov so potekale s segrevanjem reakcijske zmesi v zaprtih debelostenskih ACE cevkah, kot topilo pa sem uporabil n-BuOH. V obeh primerih so 1H NMR spektri pokazali nastanek asimetričnih stranskih produktov, ki sem jih potrdil z MS analizo. Za metodo čiščenja produktov sem uporabil prekristalizacijo iz EtOH ali MeOH, kar je bilo v večini primerov uspešno. Sinteze tiosemikarbazidnih derivatov biciklo[2.2.2]oktenov niso bile uspešne. Pri pogojih refluksa so produkti nastali v sledovih, pri pogojih segrevanja reakcijske zmesi v zaprtih debelostenskih ACE cevkah pa je prišlo do razpada in nastanka biciklo[2.2.2]oktenov s pripojenimi N-aminosukcinimidnimi obroči. Prav tako je bila neuspešna sinteza biciklo[2.2.2]oktena z N-acetaldehidnima fragmentoma.

• Language: Slovenian
• Keywords: Diels–Alder cikloadicija, biciklo[2.2.2]okten, hidrazon, acilhidrazid, tiosemikarbazid
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2022
• PID: 20.500.12556/RUL-142227
• COBISS.SI-ID: 134305283
• Publication date in RUL: 26.10.2022

Secondary language

• Language: English
• Title: Transformations of dianhydride bicyclo[2.2.2]octene frameworks into N-substituted derivatives with nucleophilic substitution on fused succinanhydride fragments

Abstract

The main emphasis of this master degree thesis is synthesis of novel compounds with bicyclo[2.2.2]octene framework. Two starting bicyclo[2.2.2]oct-7-enes with two fused succinanhydride moieties, which were used in all further derivatization reactions, were synthesized with Diels–Alder reaction of 2H-pyran-2-ones with maleic anhydride. Synthesis of a series of eighteen novel bicyclo[2.2.2]octenes with fused hydrazone moiety was achieved with nucleophilic substitution of hydrazine on cyclic anhydride fragments and subsequent reaction of N-substituted amine group with various aromatic and heteroaromatic aldehydes. In contrast to reactions of aldehydes reactions of ketones were less successful, after long reaction times only traces of desired products were observed. Bicyclo[2.2.2]octenes with fused acylhydrazide fragments were also prepared, although I was unable to isolate them in pure form. For synthesis of these compounds I prepared starting acylhydrazides from corresponding ethyl esters in reaction with hydrazine hydrate. Characterisation of acylhydrazide derivatives of bicyclo[2.2.2]octenes with 1H NMR and 13C NMR analysis was complicated by restricted rotation of acylhydrazide moieties in DMSO-d6 solution, which caused broadening of signals in the spectrum. I tried to solve this problem with measuring NMR spectra at higher temperature or in deuterated solvents with lower density. The syntheses of all aforementioned final compounds were carried out with heating the reaction mixture in closed heavy wall pressure ACE tubes. The n-BuOH was used as the solvent. In all cases the 1H NMR analysis showed the presence of asymetric by- products, which were further confirmed with MS analysis. In most cases these were removed from crude products with recrystalisation in EtOH or MeOH. The preparation of thiosemicarbazide derivatives of bicicylo[2.2.2]octenes was not successful. After refluxing reaction mixture only traces of desired products were found. When same reactions were carried out in closed heavy wall pressure ACE tubes degradation of compounds present in the reaction mixture occured, leading to the formation of bicyclo[2.2.2]octene with fused succinimide fragments. Synthesis of bicyclo[2.2.2]octene with two fused N-acetaldehyde moieties was also unsuccessful with no traces of desired products observed.

• Keywords: Diels–Alder cycloaddition, bicyclo[2.2.2]octene, hydrazone, acylhydrazide, thiosemicarbazide