Synthesis Of 2,4-disubstituted/2,3,4-trisubstitu Ted Pyrroles And Construction Of Novel Aza-BODIPY Dyes

As one kind of the important heterocyclic compounds,pyrroles are the basic core of many natural products and important precursor for various functional materials.There are many methods for efficiently constructing functionalized pyrroles,including classical methods,cycloaddition,multi-component,and metal catalyzed reactions.The 2,4-disubstituted/2,3,4-trisubstituted pyrroles are one kind of the functionalized pyrroles and important precursors for the construction of BODIPY dyes.At present,the synthesis of 2,4-disubstituted/2,3,4-trisubstituted pyrroles are only realized through Paal-Knorr synthesis and cycloaddition synthesis.And there are lots of limitation,such as limited scope of mostly 4-phenyl substituted pyrroles,difficulty in storage,explosive materials and the inability to synthesize non-phenyl-modified pyrroles.Therefore,the development of a new method for synthesizing 2,4-disubstituted/2,3,4-trisubstituted pyrroles have important practical significance.Aza-BODIPY dyes are widely used in biological and materials sciences such as fluorescence imaging,solar materials and optoelectronic devices,because they have lots of outstanding advantages,for instance,excellent chemical and photostability,intense molar absorption and high fluorescence quantum yield.A variety of phenyl-modified aza-BODIPY dyes have been reported,and pyridine and other substituent group modified aza-BODIPYs have been rarely reported.In 2007,Akkaya et al,reported a 1,7-dipyridyl-aza-BODIPY dye was used as probe to detect mercury ions.And in 2017,Chang Liu,a graduate student of our group,reported 19 structures of 1-and 7-pyridyl-aza-BODIPY dyes.Now,the 1-and 3-pyridyl-aza-BODIPY dyes have been rarely reported.Therefore,the construction of a novel pyridyl-aza-BODIPY dye can expand the platform and lay a foundation for the further application of the aza-BODIPY dyes.Based on our previous work and related research,we designed a route based on the cycloaddition reaction and it was expected to synthesize new 2,4-disubstituted/2,3,4-trisubstituted pyrroles.Through the preliminary experimental investigation with 4-vinylpyridine which was the starting compound,it was found that the 3-(pyridine-4-yl)-2H-azirine could not be constructed by this rout,indicating it was necessary to explore a new method to obtain the desired new pyrroles.There was evidence that 2H-azirine was formed during the rearrangement of oxime to generate ?-aminoketone.We expected this process could be applied to synthesize 2,4-disubstituted/2,3,4-trisubstituted pyrroles by constructing 3-substituted-2H-azirine.During the referenced process,the electron withdrawing group at ? position of oximes was more conducive to carbanion.The designed 2H-azirine had not the similar group at the same site,so a strong base was required to use for the generation of carbanion.After screening the optimal synthetic condition,we successfully explored a new route that the base was NaH and the temperature was 50°C.This new method could simply and rapidly synthesize 54 of 2,4-disubstituted/2,3,4-trisubstituted pyrroles,containing pyridine,thiophene,pyrazine etc.The results indicated the method had excellent group tolerance,and could provide strong technical support for the construction of novel BODIPY dyes.Using the new method,we constructed eight novel 1-and 3-pyridyl-aza-BODIPYs,and carried out related spectral tests.The results displayed that the introduction of pyridine into the aza-BODIPY dye could increase the Stokes shift.The 3-pyridyl caused the wavelength of the dye blue shift,and the fluorescence quantum yield increased.The 1-pyridyl caused the dye red-shift and the fluorescence quantum yield decreased.The effect of para-pyridyl is more pronounced than that of meta-pyridyl.The effects of molar extinction coefficient and half-width were different in spectral properties,due to the interaction of the substitution position and the position of the pyridinium nitrogen.The successful synthesis and testing of these series of dyes not only expand the dyes platform of aza-BODIPYs,but also provide more choices for dyes in the fields of chemical,pharmaceutical and biotechnology.In summary,we developed a new synthesize 2,4-disubstituted/2,3,4-trisubstituted pyrroles method,which is simple in synthesis,easy to store intermediates,readily available and resistant to groups.The method provided strong technical support for the construction of new BODIPY dyes.We also successfully synthesized 8 novel aza-BODIPY dyes by the synthesized 2-,4-pyridyl pyrroles,related spectral tests were carried out to determine the influence of the introduction of pyridyl on the spectral properties of aza-BODIPY dyes.This work not only provided a concise method to synthesize novel 2,4-disubstituted/2,3,4-trisubstituted pyrroles,but also provided more choices to biological and materials applications,such as fluorescence imaging and solar materials.