Chemical Properties
Isothiazole is a colorless liquid with a pyridine-like odor. It is only slightly soluble in water but readily dissolves in organic solvents such as ethanol and benzene. When treated with butyl lithium at -70°C, it undergoes lithiation at the 5-position. Isothiazole serves as a versatile intermediate for the synthesis of various 5-substituted derivatives, including alkyl groups (R-), formyl (-CHO), carboxyl (-COOH), and acyl groups (RCO-), among others. Electrophilic substitution reactions, such as nitration, sulfonation, and halogenation, predominantly occur at the 4-position.
Uses
Isothiazole, is a versatile building block that can be used in the synthesis of more complex compounds with biological activity such as the pharmaceutical drugs ziprasidone (Z485000), and perospirone (P288900).
Definition
ChEBI: Isothiazole is a mancude organic heteromonocyclic parent, a monocyclic heteroarene and a member of 1,2-thiazoles.
Preparation
Isothiazole can be prepared by the reaction of propiolic aldehyde with sodium thiocyanate to first produce 3-thiocyanatoacrolein (NCSCH=CHCHO), which is then reacted with ammonia to obtain isothiazole.
References
[1] LAI CHEN. Discovery of Novel Isothiazole, 1,2,3-Thiadiazole, and Thiazole-Based Cinnamamides as Fungicidal Candidates[J]. Journal of Agricultural and Food Chemistry, 2019, 67 45: 12357-12365. DOI:
10.1021/acs.jafc.9b03891.
[2] A. KLETSKOV. Isothiazoles in the Design and Synthesis of Biologically Active Substances and Ligands for Metal Complexes[J]. Synthesis-Stuttgart, 2019, 113 1: 159-188. DOI:
10.1055/s-0039-1690688.
[3] BERA A, PATRA P, AZAD A, et al. Neat synthesis of isothiazole compounds, and studies on their synthetic applications and photophysical properties?[J]. New Journal of Chemistry, 2022, 24: 11685-11694. DOI:
10.1039/D2NJ01962K.
[4] ZHU-ZHU ZHANG. Synthesis of Isoselenazoles and Isothiazoles from Demethoxylative Cycloaddition of Alkynyl Oxime Ethers[J]. The Journal of Organic Chemistry, 2020, 86 1: 632-642. DOI:
10.1021/acs.joc.0c02286.
