Novel Synthetic Methods And Optical Properties Of Formylpyrido[2,1-b]Benzoxazoles

This thesis mainly focuses on the development of new methods for the synthesis of formylpyrido[2,1-b]benzoxazoles and the studies on their optical properties. On the one hand, a novel reaction of o-acetaminophenols with Vilsmeier reagents was discovered, and thereout a new and simple method for convenient synthesis of 2-formylpyrido[2,1-b]benzoxazoles had been developed. On the other hand, the another product obtained from the Vilsmeier reaction of o-acetaminophenols, 2-(benzoxazol-2'-yl)-3-(dimethylamino)acroleins, refluxed in acetic anhydride to afford 4-formylpyrido[2,1-b]benzoxazoles. Finally, the UV-vis spectra and fluorescence properties of these obtained formylpyrido[2,1-b]benzoxazoles had been studied. 38 compounds were synthesized, in which 19 were new compounds. The paper comprises six chapters.Chapter 1. Introduction. In this chapter, the naming of pyrido[2,1-b]benzoxazoles was introduced, along with the advances in their synthesis and applications.Chapter 2. A novel reaction of o-acetaminophenols with Vilsmeier reagents. The reaction of o-acetaminophenol with Vilsmeier reagents in hot POCl₃ afforded a new tricyclic compound, 2-formylpyrido[2,1-b]benzoxazole (yield 12%), besides the reported compound 2-(benzoxazol-2'-yl)-3-(dimethylamino)-acrolein (yield 51%). The new compound's structure could not be elucidated by all kinds of spectrometries, including MS, HRMS, 1H NMR, 13C NMR, HMBC, IR, UV-vis and elemental analysis. According to the above spectrometries, two mostly possible structures of the new compound were proposed. Then, on the one hand, we tried to synthesize one of the possible structures, namely 4-formylpyrido[2,1-b]benzoxazole, to assist the characterization of the new compound; on the other hand, we tried to obtain its single crystals suitable for single crystal X-ray diffraction analysis. Fortunately, both of them had come true. The new compound's structure was identified as 2-formylpyrido[2,1-b]benzoxazole undoubtedly by them. The X-ray crystal structures of 2-formylpyrido[2,1-b]-benzoxazole and 4-formylpyrido[2,1-b]benzoxazole were analyzed. Finally, 6 substituted 2-formylpyrido[2,1-b]benzoxazoles were synthesized according to the new method.Chapter 3. Mechanism of the reaction of o-acetaminophenols and Vilsmeier reagents. 2-Methylbenzoxazoles was proved to be the key intermediate in the formation of 2-(benzoxazol-2'-yl)-3-(dimethylamino)-acroleins by the facts thato-acetaminophenol was quickly converted into 2-methylbenzoxazole by the action of POCl₃ in 96% yield, and 2-methylbenzoxazole reacted with Vilsmeier reagents to afford 2-(benzoxazol-2'-yl)-3-(dimethylamino)-acrolein in 90% yield. Involvement of the intermediates, which derived from the reaction of 2-methylbenzoxazole with Vilsmeier reagents, reacting with electron-rich alkenes in the formation of 2-formylpyrido[2,1-b]benzoxazole was ruled out because the addition of varied electron-rich alkenes to the reaction of o-acetaminophenol or 2-methylbenzoxazole with Vilsmeier reagents at different stages had little influence on the reaction, neither gave expected products. Based on the experiments and literatures, a probable mechanism of the reaction was proposed as follows: o-acetaminophenol was converted into imidoyl chloride firstly, intramolecular elimination of HCl leaded to the formation of 2-methylbenzoxazole, which undergone twice formylation by Vilsmeier reagents and hydrolysis to afford 2-(benzoxazol-2'-yl)-3-(dimethylamino)- acrolein; simultaneity, imidoyl chloride reacted with its tautomer enamine to eliminate HCl intermolecularly, which leaded to the formation of a dimeric imidoyl chloride, the dimer undergone intramolecular elimination of HCl, twice formylation by Vilsmeier reagents, cyclization and hydrolysis to afford 2-formylpyrido[2,1-b]-benzoxazole.Chapter 4. The synthesis of 4-formylpyrido[2,1-b]benzoxazoles. The yields of 2-(benzoxazol-2'-yl)-3-(dimethylamino)-acroleins obtained from the reaction of 2-methylbenzoxazole with Vilsmeier reagents was much higher than the reaction of o-acetaminophenol with Vilsmeier reagents in hot POCl₃ motivated us to optimize this route: o-aminophenols reacted with acetic anhydride in water to afford o-acetaminophenols, yields 98-99%; o-acetaminophenols was converted into 2-methylbenzoxazoles by the action of POCl₃ in chloroform in 93-96% yields; 2-methylbenzoxazoles reacted with Vilsmeier reagents to afford 2-(benzoxazol-2'-yl)-3-(dimethylamino)acroleins, yields 85-90%; 2-(benzoxazol- 2'-yl)-3-(dimethylamino)acroleins refluxed in acetic anhydride gave 4-formyl- pyrido[2,1-b]benzoxazoles in 32-73% yields. The total yields of 4 steps were 26-58%. Chapter 5. UV-vis spectra and fluorescence properties of formylpyrido[2,1-b]- benzoxazoles. Firstly, the UV-vis and fluorescence spectra of 2-formylpyrido[2,1-b]- benzoxazole and 4-formylpyrido[2,1-b]benzoxazole were analyzed in detail. And then, we put emphasis upon the influences of substituents and solvents on the UV-vis spectra and fluorescence properties of formylpyrido[2,1-b]benzoxazoles. For 2-formylpyrido[2,1-b]-benzoxazoles, replacement of the solvent from dichloromethane to water resulted in fluorescence quantum yield increases 0.6-9 times,with the maximum 0.18. On the contrary, for 4-formylpyrido[2,1-b]-benzoxazole, the fluorescence quantum yield decreased greatly, almostly having no fluorescence emission. We ascribed these phenomena to the formation of a coplanar six-membered ring between the two adjacent carbonyl groups of 2-formylpyrido[2,1-b]-benzoxazole and one hydrogen of water thanks to hydrogen bond, which result in an increase in the degree of conjugation and the electron density of the whole molecule due to the electron-donating property of hydroxyl hydrogen, and then lead to an increase of fluorescence quantum yield. For 4-formylpyrido[2,1-b]benzoxazole, such a coplanar six-membered ring cannot form because the two carbonyl groups locate in opposite positions, and the increase of the interaction between its excited state and solvent leads to an decrease of fluorescence quantum yield.Chapter 6. Experiments.