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## Synthesis of coumarin derivatives possessing high 2PA cross section

### Karolina Morawska

#### Abstract

Introduction. The discovery of two-photon absorption phenomena and rapid technological development of past decades have made two-photon fluorescence microscopy a widely used technique. This technique allows to obtain high-resolution three-dimensional images of studied objects as well as enables in vivo monitoring studies to be performed. The effective use of two-photon microscopy depends to a large extent on the use of appropriate fluorescent probes. That is why intensive search for compounds characterized by, among others, properties such as high two-photon absorption cross-section and high fluorescence quantum yield, is being currently carried out. Coumarin derivatives as compounds with distinctive optical properties are a potential source of effective two-photon absorption dyes. In addition to a number of applications they owe to large fluorescence (optical brighteners, photodynamic therapy and bioimaging), coumarins are known to have various biological activities widely used by the pharmaceutical industry (anti-inflammatory drugs, anti-cancer drugs and others) and a pleasant odor (perfume industry). The prevalence in nature as well as a multitude of uses makes these derivatives being of a remarkable interest among researchers. Ongoing research is being carried out to improve synthesis methods and increase library of these promising molecules. The aim of this thesis was to synthesize coumarin derivatives with a high two-photon absorption cross section and potential use in two-photon fluorescence microscopy as well as to investigate the photophysical properties of obtained compounds. Integral part of the experimental work was not only to design and synthesize appropriate functional dyes but also to measure absorption and emission spectra and to determine Stokes shift (SS), molar extinction coefficient (ε) and fluorescent quantum yield (φ) values of these compounds. Results. Three different model compounds based on benzochromen-2-one skeleton A, B, C (Fig. 4, p. 35) with potential non-linear properties, were designed. Four-step synthesis of the first one, using the Pechmann condensation followed by Scholl reaction resulted in obtaining two, heretofore unknown in the literature, compounds (4 and 5). These molecules have a rigid structure as a consequence of a fusion of naphthyl group with the coumarin skeleton. It is expected that efficient π orbitals overlap and effective relocation of charge take place in these molecules. The desire to enlarge the library of derivatives resulted in the synthesis of 4-(naphthalene-1-yl)-2H-benzo[h]chromen-2- one (6), which unfortunately did not undergo Scholl reaction under classical conditions. Compounds 4, 5, 6 in spite of small Stokes shifts, are characterized by a high fluorescence quantum yields (13%-18%). Particular expectations may be related to compound 6, as absorption and emission spectra measurements and comparison of obtained φ values show how beneficially structure stiffening influences fluorescence quantum yield. Synthesis of a second molecule afforded a 7-ethoxy-6-(imidazo[1,2-a]pyridin-2-yl)-4-methyl-2H-chromen-2-one (8). It was planned to investigate the influence of ESIPT on the fluorescence behavior of the coumarin, but as a result of spontaneous etherification which occurred while Pechmann reaction was performed, intramolecular hydrogen bond was not present in the final product. A third target was the synthesis of ethyl 6,8-dicyano-7-hydroxy-2-oxo-2H-chromene-3-carboxylate. Despite of applying many modern methods of bromine exchange it was not possible to obtain the desired compound. In total, four novel coumarin derivatives, so far not described in literature, were synthesized. Conclusions. Thanks to my research it was possible to prove that Scholl reaction can be performed for heterocyclic aromatic compounds possessing oxygen atom. This is the first successful case of application of Scholl reaction in coumarin series. This finding opens the pathway for future development in this direction. Solvent free system of the reaction favors the extension of the application of this oxidative coupling method. Absorption and emission spectra measurements and comparison of obtained quantum yield values show how the structure stiffening beneficially influences obtained φ values. Difficulties encountered when attempting to synthesize 6,8-dicyanocoumarin derivative show the detrimental effect of electron-donating hydroxyl group on reactivity of bromine atoms in coupling with cyanides.
Record ID
WUTe0a4c8c68a154b8c87f0cc8e9189f6f2
Diploma type
Master of Science
Author
Karolina Morawska Karolina Morawska,, Undefined Affiliation
Title in Polish
Synteza pochodnych kumaryny o wysokim przekroju czynnym na absorpcję dwufotonową
Supervisor
Daniel Gryko (FC/DOC) Daniel Gryko,, Department Of Organic Chemistry (FC/DOC)Faculty of Chemistry (FC)
Certifying unit
Faculty of Chemistry (FC)
Affiliation unit
Department Of Organic Chemistry (FC/DOC)
Study subject / specialization
, Biotechnologia Chemiczna - Leki i Kosmetyki
Language
(pl) Polish
Status
Finished
Defense Date
23-11-2012
Issue date (year)
2012
Keywords in Polish
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Keywords in English
-
Abstract in Polish
urn:pw-repo:WUTe0a4c8c68a154b8c87f0cc8e9189f6f2