Benzoxazole and benzothiazole comprise an important type of aromatic heterocyclic compounds with a bicyclic structure, which contains a six membered benzene ring fused with a five membered oxazole or thiazole ring on the side (Fig 1). They are common scaffolds in the biologically and pharmacological compounds, offering potential application in medicinal synthesis. It is noteworthy that benzoxazole and benzothiazole exhibit a strong toxicity to organisms, and they will generate toxic smoke through combustion. So every care should be taken during their use and storage.
Fig.1. Benzoxazole and benzothiazole compounds
Benzoxazoles and benzothiazoles are almost not water-soluble, because the bicyclic rings bring stable structure but limit the solubility. Owing to the conjugated planar structures bicyclic rings of benzoxazoles and benzothiazoles, which decide the property of high boiling point and low melting point, thus they are commonly presented as clear yellow or brown liquid. Besides, the conjugated bicyclic rings promote the red shift absorption in light spectrum, showing a visible color. All the benzoxazoles and benzothiazoles do not possess reactive group for post-application, and they are highly persistent in the environment for owned stable structure. So far, this kind of heterocyclic compounds have been employed in agriculture, biological medicine, fluorescent dye and other extensive areas.
Medicine: Benzoxazole and benzothiazole compounds have been detected in various natural medicinal molecules, motivating the synthesis of artificial derivatives to fabricate biologic precursors, which possess excellent pharmacological and physiological activities, such as antibacterial, antidiabetic, antiparasitic, anti-tumor and anti-inflammatory behavior, etc. For example, the antimicrobial activity of the benzothiazole derivatives can be optimized by adjusting different functional groups (Fig 2).
Fig.2. Chemical structure of antibacterial benzothiazole derivatives. (J. Enzyme Inhib. Med. Chem. 2013, 28, 240-266.)
Agricultural chemicals: Inspired by the antibacterial activity in medicinal precursors, benzothiazole derivatives can be applied as fungicides, insecticide, herbicide and so on. a variety of benzothiazole compounds are designed and characterized for commercial manufacture.
Dye: It is well known that a larger conjugated constitution of compund will promote the red shift of the absorption to visible region, thus the color of the benzothiazole dye can be designed via adjusting the degree of conjugation between benzene rings. Cyanine dye is a significant instance of benzothiazole dye, which is classified as symmetric or asymmetric dyes on the basis of structure (Fig 3).
Fig.3. Chemical structure of benzothiazole cyanine dyes. (Heterocycl. Commun. 2013, 19, 1-11.)
Fluorescent probe: Benzothiazole compounds contain N and S atoms that can participate in the coordination with metals, offering detectability of metalions. When the coordination with Hg2＋ occurred, the color of the probe compound (Fig 4) will change from colorless to yellow.
Fig.4. Coordination procedure of benzothiazole fluorescent probe (Chinese Journal of Organic Chemistry 2017, 37, 2221-2236.)