Sinteze i mehanizmi solvolize benzil-bromida u metanolu

master's thesis

• Title (english): Syntheses and mechanisms of solvolysis of benzyl-bromides in methanol
• Author: Medina Dedić
• Mentor: Mirela Matić (mentor)
• Committee member: Mirela Matić (predsjednik povjerenstva)
• Committee member: Bernard Denegri (član povjerenstva)
• Committee member: Kristina Pavić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of organic chemistry); Zagreb
• Defense date and country: 2024-10-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Sintetizirani su različiti benzil-bromidi uporabom odgovarajućih benzilnih alkohola i reagensa za
bromiranje, fosforovog tribromida ili acetil-bromida. Identitet dobivenih spojeva je zatim potvrđen TLC-om
i NMR-om.
Pretpostavljeno je da različiti supstituenti na aromatskom prstenu benzil-bromida različito utječu na
njihovu reaktivnost u metanolu, tj. utječu na mehanizam i brzinu reakcije nukleofilne supstitucije. Ideja ovog
rada bila je odrediti kojim mehanizmom reakcije se odvija solvoliza pojedinih benzil-bromida pomoću
Hammett-Brownove korelacijske analize u 100 % metanolu. Prvo su konduktometrijski određene konstante
brzine reakcije pri 25° C. Konstruiran je graf ovisnosti σ + o logaritmu konstanti brzine i rezultati su potvrdili
početnu pretpostavku – dobivena su dva pravca različitih nagiba (ρ + vrijednosti), čime je potvrđeno da se
solvoliza različito supstituiranih benzil-bromida u metanolu odvija različitim mehanizmom (u eksperimentu
su jedino mijenjani supstituenti na benzenskom prstenu benzil-bromida). Za oba pravca vrijednosti ρ +
su negativne i upućuju da se na reakcijskom centru formira naboj suprotan onome u referentnoj reakciji, u kojoj nastaje negativni benzoatni anion. Dakle, dokazano je da se na reakcijskom centru tijekom provođenja solvoliza različito supstituiranih benzilnih bromida formirao pozitivan naboj. Prvom pravcu pripadaju spojevi 4-metoksibenzil-bromid, 4-(metiltio)benzil-bromid i 4-fenoksibenzilbromid, čije se reakcije metanolize odvijaju SN1 mehanizmom, a nagib pravca iznosi -6,22. Može se zaključiti
da se na reakcijskom centru u prijelaznom stanju ovih spojeva generira značajno jači pozitivan naboj koji je
stabiliziran elektron-donorskom prirodom supstituenata koji zbog toga povećavaju elektronsku gustoću
reakcijskog centra, u odnosu na spojeve koji pripadaju drugom pravcu. SN2 mehanizmom se odvijaju reakcije
spojeva 3,4-dimetilbenzil-bromid, 4-metilbenzil-bromid, 4-tert-butilbenzil-bromid, 4-fenilbenzil-bromid i
3,5-dimetilbenzil-bromid, smještenih na drugi pravac nagiba -2,11. Supstituenti ovih benzil-bromida također
utječu na konstante brzina reakcija solvoliza, međutim, slabiji su elektron-donori te je stoga favoriziran SN2
mehanizam reakcije.

Abstract (english)

Various benzyl-bromides were synthesized using homologous benzyl alcohols and brominating
reagents, phosphorus tribromide or acetyl bromide. The identity of the obtained compounds was confirmed
by TLC and NMR.
It was assumed that different substituents on the aromatic ring differently affect their reactivity,
meaning they affect the mechanism and rate of the nucleophilic substitution reaction. The goal was to
determine the mechanism of solvolysis for each benzyl bromide using Hammett-Brown correlation analysis
in 100 % methanol. Reaction rate constants were first determined conductometrically at 25°C. A plot of σ
+ versus the logarithm of the rate constants was constructed, and the results confirmed the initial hypothesis –
two lines with different slopes (ρ + values) were obtained, confirming that the solvolysis of differently
substituted benzyl bromides in methanol occurs via different mechanisms (the only variable in the experiment
was the substituent on the benzyl bromides). For both lines, the ρ + values are negative, indicating that a charge opposite to that in the reference reaction, where a negative benzoate anion forms, develops at the reaction center. It was proven that a positive charge forms at the reaction center during solvolysis of differently substituted benzyl bromides. The first line
includes 4-methoxybenzyl bromide, 4-(methylthio)benzyl bromide and 4-phenoxybenzyl bromide, whose
solvolysis reactions take place by the SN1 mechanism, with a slope of -6.22. This suggests a significantly
stronger positive charge is generated at the reaction center due to their electron-donating nature, stabilizing
the carbocation intermediate. Reactions of 3,4-dimethylbenzyl bromide, 4-methylbenzyl bromide, 4-tertbutylbenzyl bromide, 4-phenylbenzyl bromide and 3,5-dimethylbenzyl bromide follow the SN2 mechanism, represented by the second line with a slope of -2.11. The substituents of these benzyl bromides also affect the reaction rate constants of solvolysis, however, they are weaker electron donors, and therefore the SN2
reaction mechanism is favored.

• Keywords: solvoliza; metanoliza; nukleofilna supstitucija; Hammett-Brownova korelacijska jednadžba
• Keywords (english): solvolysis; methanolysis; nucleophilic substitution; Hammett-Brown correlation equation
• Language: croatian
• URN:NBN: urn:nbn:hr:163:696662
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-31 15:58:34