Date of Award

3-27-2009

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Anamitro Banerjee

Abstract

Photoremovable protecting groups (PRPGs) have found extensive applications in chemical synthesis, biology/biomedicine, and photoacid-based lithography. For most applications in biomedical settings, the use of visible wavelengths is desirable in order to avoid damage from UV-radiation. To meet the demands of the numerous applications, there is continued interest in the development of PRPGs, as the current pool is limited. 1-[2-(2-Hydroxyalkyl)phenyl]ethanone (HAPE), a new photoremovable protecting group for carboxylic acids is introduced. It was synthesized from commercially available 2'-bromoacetophenone and used to protect carboxylic acids as HAPE esters in good yields. Photolysis of HAPE esters was performed with 320 nm light and the free acids were released in 56–82% yield. The proposed mechanism of photodeprotection involves a γ-H abstraction in the triplet excited state (photoenolization) leading to the formation of E and Z ground state photoenols. From literature reports and geometry optimizations, it is predicted that the E isomer is more stable and as such more likely to release the acid. To achieve the release of carboxylic acids at higher wavelength, 2-oxo-2-ferrocenylethyl esters were synthesized and tested. When photolyzed in methanol at 470 nm, phenylacetic acid was released in 66% isolated yield. Benzoic acid and tert-butoxycarbonyl (t-BOC) glycine were not released under these conditions. Styrylthiophene-like photoacid generators (PAGs) with NO2- and NH2-substituted phenyl rings were synthesized to investigate their potential as photoacid generators. The m-NO2-PAG led to oxidative cleavage of the double bond to afford carbonyl compounds when photolyzed in air using 320 mn light. In the absence of oxygen, the NO 2-PAGs were stable to photolysis under similar conditions. The nitro PAGs were reduced to their amino counterparts and photolyzed under similar conditions. Under nitrogen, the p-NH2-PAG produced a rearrangement product, due to a [1,9] Br shift after cyclization. The product, resulting from the release of HBr was isolated in 21% yield when the m-NH2-PAG (99b) was irradiated under nitrogen. For the PAGs tested, the unsubstituted PAG 97 gave the best yield (36%). New strategies were developed for the photochemical release of carbonyl compounds from alkyl enol ethers. Protected enols were synthesized in 62–97% yields. Incorporating a 2-nitrobenzyl group as the chromophore (an excited state electron acceptor), the enol ethers were photolyzed in dry acetonitrile under air using 350 nm light. Analysis of the photoproducts by GC–MS revealed a C=C bond scission, that resulted in the formation of a ketone (about 60%), while the aldehyde (from tautomerization of the corresponding released enol) was obtained as a minor product. Based on product studies, it is speculated that a photoinduced intramolecular electron-transfer from the electron rich C=C bond to the electron deficient nitrobenzyl group, followed by 1,2-dioxetane formation, is responsible for the formation of the ketone or aldehyde.

Download

Share

COinS