Oksidativno jodokloriranje alkenov in alkinov ter njihova nadaljnja pretvorba

Filip, Larisa (author), Iskra, Jernej (mentor)

Halogenirane organske spojine imajo velik pomen v farmaciji, agrokemiji in v organski sintezi, posebej pri reakcijah spajanja. V sklopu magistrskega dela smo preučevali jodokloriranje alkinov z uporabo HICl2, ki smo ga pripravili iz molekularnega joda, klorovodikove kisline in vodne raztopine vodikovega peroksida. HICl2 je bil pripravljen v mešanici topil 2,2,2-trifluoroetanol (TFE) in benzotrifluorid, ki je bil potreben zaradi slabe topnosti molekularnega joda v TFE. Najprej smo dihalogenirali trojne vezi fenilacetilena in njegovih derivatov. Večina reakcij je potekla hitro in z dobrimi izkoristki (65–90 %). Potekle so tudi reakcije, kjer trojna vez ni bila na terminalnem mestu. Reakciji, kjer sta imeli izhodni spojini na fenilnem obroču vezane elektron-donorske skupine (OMe in NH2), sta bili neselektivni. Nadalje smo raziskovali jodokloriranje alifatskih alkinov. Tudi pri alkinih, ki so bili vezani na alifatske verige, je jodokloriranje trojne vezi s HICl2 poteklo z dobrimi izkoristki (61–86 %). S pomočjo NOESY spektrov smo ugotovili, da nastajajo zgolj trans produkti jodokloriranja. V tem sklopu smo preverili tudi vpliv OH skupine na potek reakcije. Uspešno smo jodoklorirali 3-heksin-2,5-diol in tako pokazali, da tudi OH skupina ne moti reakcije s HICl2. Na koncu smo se lotili še halogeniranja alkinov, ki so vezani na ketonsko oziroma estrsko skupino. Jodokloriranje trojne vezi je poteklo tako na estrskem kot na ketonskem derivatu. V zadnjem delu raziskav smo izvedli še reakcijo spajanja z nekaterimi produkti, ki so nastali z dihalogeniranjem. Izbrali smo reakcijo spajanja katalizirano z bakrom v kateri je jodid izstopajoča skupina, medtem ko klorov atom ostane vezan. Za testiranje reakcije spajanja smo izbrali tri substrate, ki smo jih pridobili z jodokloriranjem fenilacetilena, 1-fenilprop-1-ina in heks-1-ina. Na C atom, na katerega je bil vezan jod, smo vezali 2-pirolidon. Reakcija spajanja je bila uspešna na 1-jodo-2-kloroetenilbenzenu, ki je terminalen alken, vezan na fenilni obroč. Reakcija spajanja je uspela tudi na ne-terminalnem alkenu – (2-jodo-1-kloro-1-propenil) benzen in tudi na alifatskem alkenu – 1-jodo-2-kloro-1-heksen. S tem smo potrdili uporabnost halogeniranih spojin v organski sintezi.

• Language: Slovenian
• Keywords: Jodokloriranje alkinov, regioselektivno dihalogeniranje, reakcija spajanja, zelena kemija
• Work type: Master's thesis/paper
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2024
• PID: 20.500.12556/RUL-162460
• Publication date in RUL: 24.09.2024

Secondary language

• Language: English
• Title: Oxidative iodochlorination of alkenes and alkynes and their subsequent conversion

Abstract

Halogenated organic compounds are of great importance in pharmaceuticals, agrochemistry and organic synthesis, especially when it comes to coupling reactions. As part of this master’s thesis, we studied the iodochlorination of alkynes using HICl2, which was prepared from molecular iodine, hydrochloric acid and an aqueous solution of hydrogen peroxide. HICl2 was prepared in a solvent mixture of 2,2,2-trifluoroethanol (TFE) and benzotrifluoride, which was necessary due to the poor solubility of molecular iodine in TFE. First, we dihalogenated the triple bond of phenylacetylene and its derivatives. Most reactions proceeded quickly and with good yields (65–90 %). Reactions also proceeded where the triple bond was not at a terminal position. Reactions where the starting compounds had electron-donating groups (OMe and NH2) attached to the phenyl ring were non-selective. Next, we investigated the iodochlorination of aliphatic alkynes. The reactions were successful, albeit with slightly lower yields (61–86 %). Using NOESY spectra, we determined that only trans products of iodochlorination were formed. In this context, we also examined the influence of the OH group on the reaction. We successfully iodochlorinated 3-hexyne-2,5-diol, demonstrating that the OH group does not interfere with the reaction with HICl2. Finally, we attempted to halogenate alkynes attached to ketone or ester groups. Iodochlorination of the triple bond proceeded on both ester and ketone derivatives. In the final part of the research, we performed a coupling reaction with some of the products obtained from dihalogenation. We chose copper catalyzed coupling reaction where iodine is the leaving group, while chlorine remains attached. To test the coupling reaction, we chose three substrates obtained by iodochlorination of phenylacetylene, 1-phenylprop-1-yne and hex-1-yne. We attached 2-pyrrolidone to the carbon atom previously bonded to iodine. The coupling reaction was successful with 2-chloro-1-iodoethenylbenzene, a terminal alkene attached to a phenyl ring. The coupling reaction also succeeded with a non-terminal alkene – (1-chloro-2-iodo-1-propenyl)benzene, and with an aliphatic alkene – 2-chloro-1-iodo-1-hexene. This confirmed the utility of halogenated compounds in orgaic synthesis.

• Keywords: Iodochlorination of alkynes, regioselective dihalogenation, coupling reactions, green chemistry