Title page for ETD etd-07142011-135413


Type of Document Dissertation
Author Hancock, Amber N
Author's Email Address hancocka@vt.edu
URN etd-07142011-135413
Title A Radical Approach to Syntheses and Mechanisms
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Tanko, James M. Committee Chair
Long, Timothy E. Committee Member
Madsen, Louis A. Committee Member
Marand, Hervé L. Committee Member
Marand, Hervé L. Committee Member
Troya, Diego Committee Member
Keywords
  • Carboxylate
  • Deprotonation
  • Electron Transfer
  • Radical Cyclization
  • Homolytic Substitution
  • Selenium
  • Radical Trap
  • Rate Constant
  • Deuterium Isotope Effect
  • Arrhenius Parameter
  • N
  • Mechanism
  • Kinetics
  • Cyclic Voltammetry
  • Constant Potential Coulometry
  • Competition Kinetics.
  • Amine Radical Cation
  • N-dimethylaniline
  • Digital Simulations
  • Laser Flash Photolysis
Date of Defense 2011-06-10
Availability unrestricted
Abstract
The critically important nature of radical and radical ion mechanisms in biology and chemistry continues to be recognized as our understanding of these unique transient species grows. The work presented herein demonstrates the versatility of kinetic studies for understanding the elementary chemical reactions of radicals and radical ions.

Chapter 2 discusses the use of direct ultrafast kinetics techniques for investigation of crucially important enzymatic systems; while Chapter 3 demonstrates the value of indirect competition kinetics techniques for development of synthetic methodologies for commercially valuable classes of compounds. The mechanism of decay for aminyl radical cations has received considerable attention because of their suspected role as intermediates in the oxidation of tertiary amines by monoamine oxygenases and the cytochrome P450 family of enzymes. Radical cations are believed to undergo deprotonation as a key step in catalysis. KIE studies performed by previous researchers indicate N,N-dimethylaniline radical cations deprotonate in the presence of the bases acetate and pyridine. By studying the electrochemical kinetics of the reaction of para substituted N,N-dimethylaniline radical cations with acetate anion, we have produced compelling evidence to the contrary. Rather than deprotonation, acetate reacts with N,N-dimethylaniline radical cation by electron transfer, generating the neutral amine and acetoxyl radical.

Transport properties of reactants and solvent polarity changes were investigated and confirmed not to influence the electrochemical behavior forming the basis for our mechanistic hypothesis. To reconcile our conclusion with earlier results, KIEs were reinvestigated electrochemically and by nanosecond laser flash photolysis. Rather than a primary isotope effect (associated with C-H bond cleavage), we believe the observed KIEs are secondary, and can be rationalized on the basis of a quantum effect due to hyperconjugative stabilization in aromatic radical cations during an electron transfer reaction. Product studies performed by constant potential coulometry indicate N,N-dimethylaniline radical cations are catalytic in carboxylate oxidations. Collectively, our results suggest that aminyl radical cation deprotonations may not be as facile as was previously thought, and that in some cases, may not occur at all.

Interest in design and synthesis of selenium containing heterocycles stems from their ability to function as antioxidants, anti-virals, anti-inflammatories, and immunomodulators. To establish synthetic feasibility of intramolecular homolytic substitution at selenium for preparation of selenocycles, we set out to determine what factors influence cyclization kinetics.

A series of photochemically labile Barton and Kim esters have been syntheisized and employed as radical precursors. The effect of leaving radical stability on kinetics has been investigated through determination of rate constants and activation parameters for intramolecular homolytic substitution of the corresponding radicals via competition experiments. Notable leaving group effects on measured kinetic parameters show more facile reactions for radical precursors with more stable leaving radicals. Moreover, cyclizations to form six-membered (as opposed to five- membered) ring systems exhibited order of magnitude decreases in rate constants for a given leaving radical. Our results are congruent with expectations for radical cyclizations trends for the varied experimental parameters and suggest homolytic substitution affords a convenient means for synthesis of selenocycles.

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