Date of Award
Fall 2012
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Steinmetz, Mark G.
Second Advisor
Donaldson, William A.
Third Advisor
Rathore, Rajendra
Abstract
The research focuses on the design of photoremovable protecting groups that can be used to deprotect biological substrates of an organic compound by photolysis. The deprotection of the protecting group via photolysis requires heterolysis of a bond to the substrate. Heterolysis of a C-O or C-S σ-bonds in a zwitterionic intermediate is proposed. The photochemical electrocyclic reactions studied involve acrylanilides, benzothiophene carboxanilides, and N-(9-oxothioxanthenyl) benzothiophene carboxamides. α,β-Unsaturated anilides bearing leaving groups at the allylic position of the α-methylacrylamide group undergo photochemical electrocyclic ring closure with release of leaving group which could occur directly from a photochemically produced zwitterionic intermediate or via an enolate produced upon deprotonation of zwitterionic intermediate. An accompanying minor photoproduct retaining the leaving group is thought to be formed via a 1,5-H shift of the zwitterionic intermediate. The photolysis wavelength can be 365 nm by introducing a benzoyl group into the para position of the anilide. The photochemistry derives from the singlet excited state. The most efficient photochemical electrocyclic ring closure and leaving group expulsion found thus far occurs with benzothiophene carboxanilides, which has considerable potential for use as cage compounds. A variety of leaving groups, incorporated at the C-3 position of the benzothiophene ring system are photochemically expelled completely, and the quantum efficiencies for LG- expulsion vary with basicity of the LG- over the range 0.007-0.2. The approximate dependence of log Φ on the pKa of the leaving group conjugate acid suggests that the LG- expulsion competes with ring-dissertationing of the zwitterionic intermediate. The electrocyclic ring closure to form the zwitterionic intermediate occurs in the triplet excited state. Incorporation of benzophenone chromophore by replacing the N-phenyl group of the anilide allows photolyses to be conducted at 365 nm. Thioxanthones bearing a benzothiophene carboxamide group at the C-2 position are capable of expelling leaving groups such as Cl-PhS-, HS- and PhCH2S-. The leaving group expulsions can be achieved using 390 nm light. Moreover, the inclusion of a carboxylate group at the C-6 position of the benzothiophene ring improves solubility in aqueous media. The photocyclizations occur in the triplet excited state according to quenching experiments.