Synthesis, spectroscopic characterization, and computational studies of 2-cyano-6-hydroxybenzothiazole: a key synthetic intermediate of firefly luciferin

Authors : Ghasem Shahmoradi, Saeid Amani

Pages : 1499-1517

View : 19 | Download : 10

Publication Date : 9999-12-31

Article Type : Makaleler

Abstract :Firefly luciferin is widely applied as a biotechnological tool for visualizing various biological processes in vitro and in vivo. Chemically, 2-cyano-6-hydroxybenzothiazole, as a key synthetic intermediate of firefly luciferin, is obtained from 2-cyano-6-methoxybenzothiazole by changing the methoxy with a hydroxy group. However, this approach is costly and not suited for large-scale synthesis. Here we report cost-effective and efficient syntheses of 2-cyano-6-hydroxybenzothiazole through the catalytic Sandmeyer-type cyanation reaction. Our approach employs diazonium tetrafluoroborate salt of 2-amino-6-hydroxybenzothiazole as a cyanation substrate. The cyanation reaction proceeds efficiently under mild conditions by using Cu(I)/Cu(II)/N,N,N\textquotesingle,N\textquotesingle-tetramethylethylenediamine as a catalyst. In addition, computational studies of the 2-cyano-6-hydroxybenzothiazole structure were performed based on the density functional theory method. The theoretical parameters of the optimized geometry were derived from the B3LYP/6-311$++$G(d, p) method. Time-dependent density functional theory was applied to assign the electronic absorption bands observed experimentally and the $^{1}$H NMR chemical shifts were computed using the GIAO method. There was a significant relationship between computational studies and experimental results.
Keywords : Firefly luciferin, diazonium tetrafluoroborate, Sandmeyer, 2-cyano-6-hydroxybenzothiazole, computational studies