Sinteza 1,2,4,5-tetraoksanov in njihova herbicidna učinkovitost

Ilioska, Tamara (author), Iskra, Jernej (mentor), Dolenc Koce, Jasna (co-mentor)

V okviru tega magistrskega dela smo raziskali vpliv strukture 1,2,4,5-tetraoksanov (TO) na njihovo termično stabilnost in herbicidno učinkovitost. V ta namen smo sintetizirali knjižnico dispiro-, spiro- in nespiro-TO iz aldehidov ali ketonov in vodikovega peroksida s ciklokondenzacijo katalizirano z HBF4 (0,2-2 ekv. napram karbonilnega substrata) v fluoriranem alkoholu TFE ali HFIP. Simetrične dispiro-TO sintetizane iz cikličnih ketonov smo izolirali z boljšimi izkoristki (64-76 %) kot simetrične nespiro-TO (44-46 %) sintetizirane iz acikličnih ketonov/aldehidov. Sinteza nesimetričnih TO je potekala preko tvorbe gemdihidroperoksida, ki je nastal s koncentriranjem mešanice določenega ketona in H2O2 v acetonitrilu pod znižanim tlakom. Temu je sledila ciklokondenzacija med nastalim gemdihidroperoksidom in izbranim ketonom/aldehidom v TFE/HFIP v prisotnosti HBF4. Sinteza nesimetričnih dispiro-TO je vodila do TO z zmernimi do odličnimi izkoristki (38- 93 %). Izvedena je bila nadaljnja modifikacija stranskih substituentov na cikloheksanskem obroču za vključitev dušikovega atoma v strukturo TO v obliki azidne ali amidne funkcionalne skupine. Dispiro-TO s karboksilno skupino vezano na cikloheksanski obroč smo zaestrili z 2-bromoetanolom z 72 % izkoristkom, in nato še bromov atom substituirali z azidno skupino s 87 % izkoristkom. Za redukcijo azidne skupine TO smo uporabili PPh3 v THF/H2O sistemu kot topilu. Redukcija je potekala z 38 % izkoristkom v 16 h in topilu DMF. Termična analiza sintetiziranih TO je bila izvedena z diferencialno skenirajočo kalorimetrijo (DSC). Simetrični dispiro-TO so bili termično bolj stabilni kot simetrični nespiro-TO. Vrednost temperature termičnega razpada za nesimetrične TO je bila med vrednostmi obeh simetričnih TO. Pri simetričnih dispiro-TO se je termična stabilnost povečala s polarnostjo stranskih substituent. Knjižnico TO smo uporabili za raziskovanje vpliva TO na kalitev in rast vrtne redkvice (Raphanus sativus L.). Vsi testirani TO so povzročili zaviranje kalitve semen, nekateri tudi zaviranje rasti korenin. Z merjenjem vsebnosti malondialdehida (MDA) smo posredno izmerili oksidativni stres v rastlinskih celicah, ki so bile izpostavljene različnim TO pri koncentracijah 0,015 mM, 0,15 mM, 1,5 mM, 15 mM ter 150 mM. Prisotnost simetričnega TO z estrsko funkcionalno skupino pripeto na stranski cikloheksanski obroč je pri koncentraciji 0,015 mM povzročila povečanje vsebnosti MDA v rastlinskih celicah, kar nakazuje, da je mehanizem herbicidnega delovanja tega TO povezan s povečanjem oksidativnega stresa.

• Language: Slovenian
• Keywords: 1, 2, 4, 5-tetraoksani, ciklični organski peroksidi, fitotoksična aktivnost, herbicidi, termična stabilnost, vodikov peroksid
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2022
• PID: 20.500.12556/RUL-137371
• COBISS.SI-ID: 112023811
• Publication date in RUL: 15.06.2022

Secondary language

• Language: English
• Title: Synthesis of 1,2,4,5-tetraoxanes and their herbicidal efficacy

Abstract

In the framework of this master's thesis, we studied the influence of 1,2,4,5-tetraoxanes (TO) structure on their thermal stability and potential herbicidal activity. For this purpose, we synthesized a library of dispiro-, spiro- and nonspiro-TO from aldehydes or ketones and H2O2 through acid-catalyzed cyclocondensation. Different amounts of HBF4 (0.2-2 eq. relative to the carbonyl substrate) were used in the syntheses in fluorinated alcohols TFE or HFIP as solvents. Symmetric dispiro-TO synthesized from cyclic ketones had better yields (64-76%) than symmetric nonspiro-TO (44-46%) synthesized from aliphatic acyclic ketones/aldehydes. Asymmetric TOs were synthetised from gem-dihydroperoxide, formed by concentrating a mixture of the chosen ketone and H2O2 in acetonitrile under reduced pressure. This was followed by cyclocondensation of the resulting gem-dihydroperoxide and the selected ketone/aldehyde in TFE / HFIP in the presence of HBF4. The synthesis of asymmetric dispiro-TOs led to TOs with moderate to high yields (38-93%). Further modification of the substituents at the cyclohexane ring was performed to incorporate a nitrogen atom into the TO structure as an azide or amide functional groups. A selected TO with carboxylic acid bound to cyclohexane ring was esterified with 2-bromoethanol with 72% yield, and then bromine was substituted with an azide group with 87% yield. PPh3 in THF/H2O solvent was used to reduce the azide group on the TO. The reduction was performed for 16 h in DMF and yielded 38% of the product. Thermal analysis of the synthesized TOs was performed by differential scanning calorimetry (DSC). Symmetric dispiro-TOs were thermally more stable than symmetric nonspiro-TOs. The value of the thermal decomposition temperature for asymmetric TOs was between the values of both corresponding symmetric TOs. In symmetric dispiro-TO, thermal stability increased as the polarity of the side substituents increased. The TO library was used to investigate the effect of TO on the germination and growth of radish (Raphanus sativus L.). All TO tested showed inhibition of seed germination, some also showed an inhibition of root growth. We indirectly measured the oxidative stress in plant cells exposed to different TOs at concentrations of 0.015 mM, 0.15 mM, 1.5 mM, 15 mM, and 150 mM by measuring the malondialdehyde (MDA) concentration. Treatment with 0,015 mM symmetric TO with cyclohexane ring bearing ester group as a side substituent resulted in increase of MDA concentration.

• Keywords: 1, 2, 4, 5-tetraoxanes, cyclic organic peroxides, herbicides, hydrogen peroxide, phytotoxic activity, thermal stability