Long-wavelength Fluorogenic Derivatization of Aryl Halides Based on the Formation of Stilbene by Heck Reaction with Vinylbenzenes

Abstract

The long-wavelength fluorogenic derivatization method for aryl halides was developed based on the stilbene formation by the Heck coupling reaction between aryl halides and vinylbenzenes in the presence of palladium (II) acetate as a catalyst.Fluorescent maximum wavelengths of the derivative obtained by the proposed reaction were 365-450 nm, which were 50-100 nm longer than those of the biphenyl derivatives formed with the our previously developed fluorogenic derivatization method. Also, by the investigation using vinylbenzenes that containing electron-donating or -withdrawing functional groups, an internal charge transfer system could contribute to extend emission wavelength of the derivative. Furthermore, the proposed reaction was applied to develop a pre-column derivatization HPLC with fluorescence detection method for aryl bromides using 4-vinylanisole. p-Substituted aryl bromides (i.e., p-bromobenzonitrile, p-bromoanisole, bromobenzene, p-bromobenzoic acid ethyl ester, p-bromotoluene) derivatives were successfully detected within 40 min with the detection limit of 0.007-0.264 µM. Despite the short reaction time of 10 min, the reaction yields for pbromoanisole and bromobenzene were good at 101% and 87%, respectively.

Unique biomedical application of fluorescence derivatization based on palladium‐catalyzed coupling reactions for HPLC analysis of pharmaceuticals and biomolecules

“…In the previously discussed application of Mizoroki-Heck coupling, DIBI was used as a FL labeling reagent for alkenes. However, the Mizoroki-Heck coupling application was not limited to alkene analysis, as it was next used by our research group (Higashijima et al, 2020) and Sewald research group (Gruß et al, 2019) for fluorogenic derivatization of aryl bromides using styrene derivatives, forming highly fluorescent stilbene derivatives. The reaction schemes are shown in Figure 16.…”

“…Based on stilbene production via the Mizoroki-Heck coupling reaction between aryl halides and vinyl anisole in the presence of Pd(II) acetate as a catalyst, a long-wavelength fluorogenic derivatization technique for aryl halides was reported by our research group (Higashijima et al, 2020). The reaction scheme is shown in Figure 16 ( allowed their analysis in biological fluids and spice products (Fukuda et al, 2022;Kishikawa et al, 2011;Takada et al, 2022).…”

“…The FL spectra of the Mizoroki–Heck coupling reaction product between p ‐vinyl anisole and p ‐bromobenzoic acid ethyl ester, where (b) and (d) are the excitation and emission spectra of the p ‐vinyl anisole reagent blank and (a) and (c) are the excitation and emission spectra of the p ‐vinyl anisole‐aryl bromide derivative. Source : reprinted with permission from Higashijima et al (2020) © Springer Nature.…”

“…The concentration of methoxy bromobenzene was 10 μ m , and that of all the other samples was 100 μ m . Source : reprinted with permission from Higashijima et al (2020)© Springer Nature.…”

Simple Fluorescence Assay for Triethylamine Based on the Palladium Catalytic Dimerization of Benzofuran-2-boronic Acid

“…Palladium-catalyzed cross-coupling reactions are considered to be efficient to construct carbon-carbon bonds. [1][2][3] The Suzuki-Miyaura coupling reaction is a palladium-catalyzed crosscoupling process between aryl halides and aryl boronic acids, and has been widely used to synthesize various chemicals including pharmaceutics due to the stability of the reagents. [4][5][6] In the case of the Suzuki-Miyaura coupling reaction, bases including amines are frequently added to activate aryl boronic acids in order to achieve a higher reaction yield.…”