Synthesis and Derivatization of Julolidine: A Powerful Heterocyclic Structure

Abstract

Julolidines constitute a class of N‐heterocycle compounds which have in common the 2,3,6,7‐tetrahydro‐1H,5H‐benzo[1,2]quinolizine ring. Due mainly to its fluorescence properties, such structures have shown potential application in a range of scientific and technological areas and have attracted attention of a great variety of research groups. For example, julolidines have been used for detection of ions and volatile compounds in environmental and biological samples, to the construction of dye‐sensitized solar cells, photoconductive materials and as fluorescent sensors for bioimaging. This review summarizes the strategies reported to the synthesis of the julolidine ring and the principal modifications for obtaining more complex julolidine derivatives with improved fluorescence properties of these compounds. In this context, aldol condensation, olefination, imine synthesis, and cross‐coupling reactions have been extensively explored and discussed. Examples of applications, which illustrate the great potential of such structures, will also be briefly presented.

Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

“…Prior to the present work, and to our knowledge, only three examples of unsymmetrical pyronin dyes have been described in the literature, 1 [24], DQF594 [44] and AR116 [40] (Fig. The marked difference between 2 and 3 in the efficacy of intramolecular cyclization/dehydration domino process (after Boc removal) may be explained by superior rigidity of julolidine fragment that favors a coplanar structure for bis-aryl ether intermediate and hence the spatial proximity between reactive formyl group and phenylogous amine [59]. As in the case of 2, twice chromatographic purifications (flash-chromatography over silica gel followed by semi-preparative RP-HPLC) gave unsymmetrical pyronin dye 3 in a pure form (>95%), as a TFA salt and with an isolated yield of 16%.…”

“…xanthene fluorophore bearing them, giving large increase in fluorescence quantum yield [59,62,64] as the result of reduced rotational or vibrational deactivation pathways of the excited state. This feature has been observed with the triptych AR116/2/3, as the FF value changes from 7% to 72%-76% for an emission maximum being in the wavelength range 540-560 nm.…”

Selective Modification for Red‐Shifted Excitability: A Small Change in Structure, a Huge Change in Photochemistry

“…Rivera‐Fuentes and co‐workers published a comparison of azetidinyl‐coumarin (Az‐CM) and the widely used blue‐absorbing PPG diethylaminocoumarin (DEACM) regarding their photolysis efficiency (Figure 1). [11] A third derivative carried a julolidine [12] substituent, where rotation around the N‐C (donor) bond was prohibited due to the connection of the 6‐membered alkyl‐rings to the aromatic system. Interestingly, julolidine‐ and azetidinyl‐coumarin showed a highly similar behavior in all experiments.…”

Synthetic routes to novel fluorogenic pyronins and silicon analogs with far-red spectral properties and enhanced aqueous stability

“…The resulting mixed bis-aryl ether 8 was next subjected to the acidic conditions TFA-DCM (9:7, v/v) found to be effective for its conversion to pyronin dye Gratifyingly, we noted that the reaction is complete within 30 min without requiring heating. Synthesis of unsymmetrical pyrionin dyes 2 and 3 (FC (SiO2) = flash-column chromatography over silica gel, O/N = overnight, RT = room temperature).The marked difference between 2 and 3 in the efficacy of intramolecular cyclization/dehydration domino process (after Boc removal) may be explained by superior rigidity of julolidine fragment that favors a coplanar structure for bis-aryl ether intermediate and hence the spatial proximity between reactive formyl group and phenylogous amine[59].CuI, picolinic acid, K 3 PO 4 , DMSO, 90 °C, O/N…”

“…Since no study has ever compared absorption properties of a xanthene scaffold bearing either N-methylindoline or julolidine moieties as tertiary aniline units[66], the present work helps to show that the first one is less effective to cause a significant bathochromic shift and may even be regarded as a weaker electron donor than the conventional diethylamino group. Conversely, both Nmethylindoline and julolidine moieties are known to readily promote rigidization of the core xanthene fluorophore bearing them, giving large increase in fluorescence quantum yield[59,62,64] as the result of reduced rotational or vibrational deactivation pathways of the excited state. This feature has been observed with the triptych AR116/2/3, as the FF value changes from 7% to 72%-76% for an emission maximum being in the wavelength range 540-560 nm.Although unsymmetrical pyronin dyes 2 and 3 exhibit a more pronounced hydrophobic character, especially the julolidine derivative, no formation of non-emissive H-type aggregates occurred in neutral aq.…”