Sinteza različito supstituiranih benzhidrilnih dietil-fosfata

master's thesis

• Title (english): Synthesis of differently substitued benzhydryl diethyl phosphates
• Author: Nicole Gerić
• Mentor: Mirela Matić (mentor)
• Committee member: Mirela Matić (predsjednik povjerenstva)
• Committee member: Sandra Jurić (član povjerenstva)
• Committee member: Suzana Inić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of organic chemistry); Zagreb
• Defense date and country: 2018-04-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Zbog značajne uloge organofosfata u mnogim važnim fiziološkim procesima, do danas je osmišljeno više načina njihove sinteze. Za potrebe ovog rada sintetizirani su spojevi: 4,4'-dimetilbenzhidrilni dietil-fosfat, 4-metilbenzhidrilni dietil-fosfat, 4-fluorbenzhidrilni dietil-fosfat te nesupstituirani benzhidrilni dietil-fosfat. Navedeni spojevi dobiveni su nukleofilnom supstitucijom u reakciji srebrovog dietil-fosfata i različito supstituiranih benzhidrilnih bromida/klorida uz izdvajanje srebrovog bromida/klorida. Prvi korak sinteze bila je redukcija odgovarajućih benzhidrilnih ketona u alkohole (benzhidrole). Dobiveni benzhidroli su bromirani pri čemu su nastali benzhidrilni bromidi, reaktivniji međuprodukti s dobrom izlaznom skupinom.
Za dobivanje željenih produkata, benzhidrilnih dietil-fosfata, također je bilo potrebno pripremiti srebrov dietil-fosfat koji je sintetiziran iz dietil-klorfosfata i srebrovog (I) oksida.
Za sintezu su izabrani upravo ovi supstituirani benzhidrilni fosfati jer su tim spojevima naknadno izmjerene konstante brzine solvolize konduktometrijskom metodom u različitim protonskim i neprotonskim otapalima kako bi se naposlijetku odredila heterolitička reaktivnost dietil-fosfatne izlazne skupine.

Abstract (english)

Due to the significant role of organophosphates in important physiological processes, many methods of their synthesis have been developed. For the purpuse of this thesis, the following compounds were synthesized: 4,4'-dimethylbenzhydryl diethyl phosphate, 4-methylbenzhydryl diethyl phosphate, 4-fluorobenzhydryl diethyl phosphate and unsubstitued benzhydryl diethyl phosphate. These compounds are the result of a nucleophilic substitution in the reactions of silver diethyl phosphate and differently supstituted benzhydryl bromides/chlorides which were followed with removal of silver bromide/chloride.
The first step of the synthesis was the reduction of corresponding benzhydryl ketons into alcohols (benzhydrols). Those benzhydrols were refluxed with acethyl bromide giving benzhydryl bromides, more reactive intermediates with better leaving groups.
To obtain wanted products, benzhydryl diethyl phosphates, it was also necessary to prepare silver diethyl phosphate from diethyl chlorophosphate and silver (I) oxide.
Synthesis of these specific compounds was chosen due to subsequently measured solvolytic rate constants in different protic and aprotic solvents. This was done conductometrically with the goal to determinate heterolitic reactivity of the diethyl phosphate leaving group.

• Keywords: sinteza; organofosfati; benzhidrilni bromidi; benzhidrilni dietil-fosfati; NMR
• Keywords (english): synthesis; organophosphates; benzhydryl bromides; benzhydryl diethyl phosphates; NMR
• Language: croatian
• URN:NBN: urn:nbn:hr:163:640949
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-12-12 15:53:11