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And Para-Substituted Allyl Phenyl Ethers Was Investigated

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And Para-Substituted Allyl Phenyl Ethers Was Investigated Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers William Thomas Möller Faculty of Physical Sciences University of Iceland 2020 Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers William Thomas Möller 60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Organic Chemistry Advisor Benjamín Ragnar Sveinbjörnsson MS Committee Benjamín Ragnar Sveinbjörnsson Krishna Kumar Damodaran Master’s Examiner Haraldur Garðarsson Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Reykjavik, May 2020 Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers Claisen rearrangement of substituted allyl phenyl ethers (50 characters including spaces) 60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Chemistry Copyright © 2020 William Thomas Möller All rights reserved Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Hjarðarhagi, 2-6 107, Reykjavik Iceland Telephone: 525 4000 Bibliographic information: William Thomas Möller, 2020, Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers, Master’s thesis, Faculty of Physical Science, University of Iceland. Printing: Háskólaprent, Fálkagata 2, 107 Reykjavík Reykjavik, Iceland, June 2020 Abstract The regioselectivity of Claisen rearrangement with different meta-substituted and meta- and para-substituted allyl phenyl ethers was investigated. The main results were that in meta- substituent Claisen rearrangements the regioselectivity depends roughly on the electronic nature of the substituent. When the substituent is electron donating it favors the migration to unhindered side while when the substituent is electron withdrawing it favors migration towards the meta-substituent. In meta- and para-substituted aromatic Claisen rearrangement the results indicated that the para substituent does have influence on the A:B ratio. In most cases it seemed to amplify the preference of the meta-substituents. Two meta substituents were tried, methyl and chlorine with various other para-substituents. When methyl and chlorine were in meta position with hydrogen in para position they both preferred formation of isomer B. In most cases when hydrogen in para position was switched out for other substituents isomer B was still preferred. Theoretical calculations were performed on allyl phenyl ethers with different meta substituents and meta- and para-substituents. The calculations were mostly in agreement with experimental data and in some cases, it could possibly explain different behavior than was expected. For example, an allyl phenyl ether with methyl as meta-substituents gave A:B ratio 1:1.20 but the methyl group was expected to be electron donating which should form more of isomer A. The calculations did predict that isomer A was lower in energy than isomer B, but that transition state of B was lower in energy than transition state of A suggesting the temperature for the reaction probably needed to be higher to get more of A. Population analysis were performed with Mulliken, Löwdin, Hirshfeld and natural population analysis to analyze the influence of the substituents on the atomic charges on the reaction sides of the aryl and allyl group in the allyl phenyl ether. In fact, it was observed that the atomic charge on the carbon that forms the more dominant isomer is of higher negativity than the atomic charge on the carbon that forms the lesser isomer. When plotting the difference between the two carbon on the aryl ring versus B:A ratio a notable trend was observed. The atomic charges calculation methods were not always in agreement though. For example, NPA and MPA fail to agree with the other methods for Claisen rearrangement of allyl phenyl ether with fluorine as the meta substituent. This would have to be studied further with more methods! Molecular orbital composition analysis was done on few allyl phenyl ethers. The analysis predicted there to be orbital coefficients on the allyl group for allyl phenyl ethers with fluorine, methyl and ethyl as substituents. When the calculations were expanded to more complex molecules, like allyl phenyl ethers with chlorine and bromine as meta-substituents the model failed to predict coefficients on the allyl group suggesting that, presumably, another level of theory could be better with better basis sets. Útdráttur Svæðisvendni fyrir Claisen umröðun á nokkrum meta setnum og meta og para setnum allýl phenýl eterum var rannsökuð. Helstu niðurstöður rannsóknarinnar fyrir meta setnu allýl phenýl eterana er að svæðisvendnin veltur gróflega á elektrónískum áhrifum frá meta hópnum. Þegar hópurinn er rafgefandi þá mjakast allýl hópurinn í átt að óhindraði stöðunni til að mynda byggingarhverfu A og þegar hópurinn er raftogandi þá vill allýl hópurinn fara í átt að meta hópnum til að mynda byggingarhverfu B. Í Claisen umröðun þegar það eru meta og para hópar var fundið út að para hópurinn hefur áhrif á A:B hlutfallið. Í mörgum tilfellum virðist vera að para hópurinn magnar áhrifin frá meta hópnum. Tveir meta hópar voru prufaðir, metýl og klór með mörgum mismunandi para hópum. Þegar metýl og klór hóparnir voru í meta stöðu með vetni í para stöðu þá myndaðist meira af byggingarhverfu B og í mörgum tilfellum þegar vetni í para stöðu er skipt út fyrir aðra hópa þá myndaðist samt meira af byggingarhverfu B. Kennilegir reikningar voru framkvæmdir á völdum allýl fenýl eterum með mismunandi meta hópa og meta og para hópa. Reikningarnir pössuðu nokkuð vel við niðurstöður frá tilraununum og í sumum tilvikum geta reikningarnir hugsanlega útskýrt frávik. Eins og í tilfelli Claisen umröðunar þar sem metýl er meta hópur og A:B hlutfallið var 1:1.20 en búist var við að metýl hópurinn væri rafgefandi og meira af byggingarhverfu A átti að myndast. Reikningarnir sýndu að varmafræðilega ætti meira að myndast af byggingarhverfu A. Hins vegar sýndu reikningar að byggingarhverfa B væri hraðafræðilega ákjósanlegri og að hugsanlega gæti það verið að spila inní afhverju hlutfallið er B í vil. Hugsanlega gæti þurft að hafa hærri hita fyrir sumar Claisen umraðanirnar til að fá meira af varmafræðilega myndefninu. Reikningar voru framkvæmdir með Mulliken, Löwdin, Hirshfeld og náttúrulegri fjölda greiningum (e. population analysis) til að sjá hvort mismunandi sethópar hefðu áhrif á atóm hleðslur innan sameindanna. Helst var þá skoðað hvernig atóm hleðslurnar breyttust á kolefnunum sem taka þátt í umröðuninni á arýl hringnum og allýl hópnum. Helstu niðurstöður frá þeim reikningum voru þær að mismunandi sethópar hafa áhrif á atóm hleðslurnar og er það kolefni sem tekur þátt í að mynda nýtt kolefnis-kolefnis tengi í Claisen umröðuninni sem myndar meira af einni byggingarhverfu með hærri neikvæða hleðslu heldur en kolefnið sem tekur þátt í að mynda kolefnis-kolefnis tengi af þeirri byggingarhverfu sem myndast minna af. Þær kenningar sem voru prufaðar sýndu þó ekki alltaf sömu niðurstöðu. Í tilfelli þar sem meta hópur er flúor voru MPA og NPA ekki í samræmi við aðrar niðurstöður sem gefur til kynna að þetta þarf að skoða betur. Reikningar voru framkvæmdir til að finna út samsetningu sameinda svigrúmanna. Það er að segja hversu mikið af sameinda svigrúminu situr á hverju atómi. Reikningarnir sýndu fram á að sameinda svigrúmin sitja á kolefnunum á allýl hópnum þegar meta hóparnir eru metýl, etýl og flúor. Þegar reikningarnir voru framkvæmdir fyrir flóknari kerfi með stærri atóm eins og klór og bróm þá sýndu þeir ekki sömu niðurstöðu sem gæti þýtt að það þurfi að prufa reikningana með annarri kenningu fyrir reikninga innan skammtafræðinnar. Dedication I want to dedicate the work of this research to my parents. My mother who loved and raised me and my father who worked away from home for many days of the year so we would never need anything and for being my biggest role model in the world! Table of Contents List of Figures .............................................................................................................. viii List of Tables ................................................................................................................. xii Acknowledgements ........................................................................................................ xv 1 Introduction ................................................................................................................. 1 2 Results and Discussions ............................................................................................... 5 2.1 Sample definition and ratio determination ............................................................ 5 2.2 Meta-substituted Allyl Phenyl Ethers ................................................................... 8 2.3 Meta- and para-substituted Allyl Phenyl Ethers .................................................. 12 2.4 Theoretical calculations ..................................................................................... 15 2.4.1 Reaction energies ...................................................................................... 15 2.4.2 Population analysis and atomic charges ..................................................... 18 2.4.3 Molecular orbital analysis ......................................................................... 25 3 Conclusions ...............................................................................................................
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