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

Firefly luciferin is widely applied as a biotechnological tool for visualizing various biological processes invitro and in vivo. Chemically, 2-cyano-6-hydroxybenzothiazole, as a key synthetic intermediate of firefly luciferin, isobtained from 2-cyano-6-methoxybenzothiazole by changing the methoxy with a hydroxy group. However, this approachis 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 diazoniumtetrafluoroborate salt of 2-amino-6-hydroxybenzothiazole as a cyanation substrate. The cyanation reaction proceedsefficiently under mild conditions by using Cu(I)/Cu(II)/N,N,N',N'-tetramethylethylenediamine as a catalyst. In addition,computational studies of the 2-cyano-6-hydroxybenzothiazole structure were performed based on the density functionaltheory 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 observedexperimentally and the 1 H NMR chemical shifts were computed using the GIAO method. There was a significantrelationship between computational studies and experimental results.

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