Reaktivnost i efekti stabilizacije difenil-fosfinata

master's thesis

• Title (english): Reactivity and effects of stabilization of diphenylphosphinate
• Author: Ivana Tarandek
• Mentor: Mirela Matić (mentor)
• Committee member: Mirela Matić (predsjednik povjerenstva)
• Committee member: Bernard Denegri (član povjerenstva)
• Committee member: Jasna Jablan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of organic chemistry); Zagreb
• Defense date and country: 2019-06-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Spojevi 4-fluorbenzhidril-difenil-fosfinat, 4-metilbenzhidril-difenil-fosfinat, 4,4'-
dimetilbenzhidril-difenil-fosfinat i 4-metoksibenzhidril-difenil-fosfinat sintetizirani su reakcijom
odgovarajućeg benzhidrilnog bromida sa srebrovom soli difenil-fosfinata u acetonitrilu uz vrlo
visoko iskorištenje (iznad 90%). Konduktimetrijskom metodom su određene konstante brzine
solvolize sintetiziranih spojeva u 60%-tnoj vodenoj otopini acetonitrila te 60%-tnoj i 80%-tnoj
vodenoj otopini etanola. U... More navedenim otapalima u prvom stupnju razgradnje spojeva nastaju
različito supstiturani benzhidrilni kation, odnosno elektrofug i difenil-fosfinatna izlazna skupina,
odnosno nukleofug. Izmjerene vrijednosti logaritama konstanti brzine solvolize, log k korelirane su
s Ef vrijednostima korištenih referentnih elektrofuga te su dobiveni pravci ovisnosti log k/Ef
visokog stupnja korelacije (R2 > 0,994) koje opisuje LFER (linear free energy relationship)
jednadžba: log k = sf (Ef + Nf). Iz korelacijskih dijagrama log k/Ef određeni su parametri
nukleofugalnosti Nf i sf za difenil-fosfinatnu izlaznu skupinu: u 60%-tnom acetonitrilu Nf/sf =
0,08/0,86; u 60%-tnom etanolu Nf/sf = 0,49/0,89; u 80%-tnom etanolu Nf/sf = 0,19/0,93. Ako se
uzmu u obzir postojeće prethodno određene Nf vrijednosti drugih nukleofuga u različitim
otapalima, difenil-fosfinatna skupina spada u skupinu umjereno reaktivnih izlaznih skupina. U
skladu s očekivanjima, heterolitička reakcija je brža u otapalu s većim udjelom vode (60%-tni
etanol u odnosu na 80%-tni). Budući da je acetonitril aprotično otapalo, u etanolnim vodnim
otopinama su određene veće Nf vrijednosti difenil-fosfinatne skupine. Uslijed različitih nagiba
pravaca (sf) log k/Ef u 60%-tnom acetonitrilu i 80%-tnom etanolu, dolazi do njihove
konvergencije, tj.inverzije relativne reaktivnosti. NBO (Natural bond orbital) analizom je ispitana
delokalizacija elektronske gustoće stabilne konformacije supstrata i izlazne skupine te je
ustanovljeno da na stabilnost izlazne skupine tijekom solvolitičkog prijelaznog stanja utječe
negativna hiperkonjugacija u kojoj sudjeluju fosfor i dva kisikova atoma vezana za fosfor. Less

Abstract (english)

The following compounds were synthesized: 4-fluorobenzhydryl diphenylphosphinate,
4-methylbenzhydryl diphenylphosphinate, 4,4'-dimethylbenzhydryl diphenylphosphinate,
4-methoxybenzhydryl diphenylphosphinate from the corresponding benzhydryl bromide and silver
diphenylphosphinate in acetonitrile giving very high yields (above 90%). Synthesized compounds
were subjected to solvolysis in 60% aq. acetonitrile, 60% aq. ethanol and 80% aq. ethanol. In
mentioned solvents, in the first stage of... More the degradation of the compounds, X, Y-substituted
benzhydryl cation, i.e. electrofuge and diphenylphosphinate leaving group, i.e. nucleofuge are
formed. The measured values of the logarithms of the rate constants of solvolysis, log k are
correlated with Ef parameters of the used reference electrofuge and plots log k vs Ef of the high
degree of correlation (R
2 > 0,994) were constructed. Using correlation diagrams and LFER (linear
free energy relationship) equation log k25°C = sf (Nf + Ef), nucleofuge-specific parameters Nf and sf
for diphenylphosphinate leaving group were obtained: in 60% aq. acetonitrile Nf/sf = 0,08/0,86; in
60% aq. ethanol Nf/sf = 0,49/0,89; in 80% aq. ethanol Nf/sf = 0,19/0,93. If the nucleofuge – specific
parameters of other leaving groups are taken into account, diphenylphosphinate belongs to the
group of intermediate strong nucleofuges. As expected, heterolytic reaction is faster in solvent
with higher amount of water (60% aq. ethanol vs. 80% aq. ethanol). Since acetonitrile is an aprotic
solvent, in aqueous solutions of ethanol were determined higher Nf values of diphenylphosphinate.
Due to different slopes of correlation log k/Ef in 60% aq. acetonitrile and 80% aq. ethanol,
convergence appears, i.e. inversion of relative reactivity. Delocalisation of the electron density of
stable substrate conformation and leaving group was examined by NBO (natural bond orbital)
analysis. It has been found that the stability of the leaving group during the solvolytic transition
state is influenced by the negative hyperconjugation in which phosphorus and two oxygen atoms
bound to phosphorus are involved. Less

• Keywords: solvoliza; nukleofugalnost; difenil-fosfinat; negativna hiperkonjugacija
• Keywords (english): solvolysis; nucleophugality; diphenylphosphinate; negative hyperconjugation
• Language: croatian
• URN:NBN: urn:nbn:hr:163:863918
• 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: 2020-02-21 16:10:55