(+)-izokamfolenska kislina – neraziskan substrat za sintezo potencialnih dišav

Prosenak, Kaja (author), Grošelj, Uroš (mentor)

Pri eksperimentalnem delu za magistrsko nalogo sem se posvetila sintezi derivatov (+)-izokamfolenske kisline. Derivati kamfolenskega aldehida, ki imajo endociklično dvojno vez, se v industriji uporabljajo kot dišavne spojine. Izokamfolenski aldehid ima dvojno vez zunaj obroča, njegovi derivati pa tako še niso patentirani. Zato sem se posvetila pretvorbam, ki izhajajo iz izokamfolenskega skeleta. Najprej sem iz (+)‑izokamfolenske kisline pripravila nekaj izhodnih spojin, ki so služile kot iztočnica za nadaljnje reakcije. Z redukcijo sem pripravila alkohol, s selektivno oksidacijo slednjega pa aldehid. Alkohol sem zaetrila, metilni ester sem pripravila iz kisline. Iz kisline sem prav tako pripravila Weinrebov amid, ki sem ga uporabila za sintezo ketonov. Aldehide sem reagirala z Wittigovimi reagenti, pri čemer so se tvorili produkti z raznolikimi vonji – nekatere spojine so imele sladke vonjave, druge pa vonj po smrekovi smoli in meti. Aldehide sem reducirala z uporabo različnih Grignardovih reagentov, s čimer sem tvorila sekundarne alkohole. Produkti so imeli svež vonj po meti ali zeliščih. Iz izokamfolenskega alkohola sem z Appelovo reakcijo pripravila bromid, vendar je med reakcijo prišlo do premestitve dvojne vezi v obroč. Kljub temu da sem s tem zašla na območje spojin, že navedenih v literaturi, sem iz dobljenega bromida poskusila pripraviti ustrezen Wittigov in Grignardov reagent. Reakciji nista bili uspešni. Posvetila sem se tudi reakcijam, v katere je vključena metilidenska skupina. To sem epoksidirala z meta‑kloroperoksibenzojsko kislino. Z uporabo reakcije oksimerkuriranja sem tvorila metilni eter na dvojni vezi C=C. Prav tako sem eksociklično dvojno vez ciklopropanirala s Simmons‑Smith reakcijo in na ta način pripravila nekaj zanimivih produktov, vonji katerih so bili precej raznoliki. Nekateri so imeli svež, drugi bolj sladek vonj. Izolirala sem tudi spojino, ki je imela vonj po rumu. Ciklopropanirala sem Weinrebov amid, ki sem ga nato reagirala z Grignardovimi reagenti in tako pripravila ciklopropanirane ketone, ki so imeli vonj po evkaliptusu, smrekovih vršičkih ter zeliščih.

• Language: Slovenian
• Keywords: (+)-izokamfolenska kislina, ciklopropaniranje, dišavne spojine
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2023
• PID: 20.500.12556/RUL-149529
• COBISS.SI-ID: 164253187
• Publication date in RUL: 07.09.2023

Secondary language

• Language: English
• Title: (+)-Isocampolenic acid – an unexplored substrate for the synthesis of potential fragrances

Abstract

During my master's thesis, I synthesized some derivatives of (+)‑isocampholenic acid. Derivatives of campholenic aldehyde, which possesses an endocyclic double bond, are used as fragrance compounds in the industry. Since isocampholenic aldehyde has double bond outside the cyclopentane ring, its derivatives remain unpatented. Therefore, I focused on reactions based on the isocampholenic framework. Firstly, I prepared several compounds from (+)‑isocampholenic acid, which served as a starting point for further reactions. Using reduction reaction, isocampholenic alcohol was obtained and was afterwards selectively oxidized to form an aldehyde. Additionally, I synthesized a methyl ether from the alcohol using Williamson ether synthesis. The Weinreb amide was prepared from (+)‑isocampholenic acid and was later used for ketone synthesis. Reactions between the aldehyde and different Wittig reagents yielded products with various aromas – some compounds had sweet scents, while others smelled like pine resin or mint. Reactions between Grignard reagents and isocampholenic aldehyde resulted in the formation of secondary alcohols. Isolated products had fresh scents of mint and herbs. I prepared a bromide from isocampholenic alcohol using the Appel reaction, which inadvertently caused a rearrangement of the double bond into the cyclopentane ring. Despite venturing into the domain of compounds that are already documented in the literature, I attempted to prepare the corresponding Wittig and Grignard reagents from the bromide. Unfortunately, both reactions were unsuccessful. Furthermore, I tried to incorporate the double bond within the scope of the studied reactions. Using meta‑chloroperoxybenzoic acid, I formed an epoxide. With the use of an oximercuration reaction, an ether was formed from a double C=C bond. Double bond was also cyclopropanated using the Simmons‑Smith reaction, resulting in several interesting products with diverse scents, including fresh, sweet and rum‑like fragrances. Weinreb amide was cyclopropanated as well and the resulting product was subsequently reacted with Grignard reagents, yielding cyclopropanated ketones with scents of eucalyptus and spruce buds, while the scent of others could be described as herbal.

• Keywords: (+)‑Isocampholenic acid, cyclopropanation, fragrances