Nitrogen and sulfur containing heterocyclic compounds such as thiazoles are of great practical and fundamental interest. Development of novel synthetic strategies for the synthesis of thiazole derivatives with various substitution pattern have received considerable attention in the field of pharmaceutical and biomedical chemistry.1-5 Particularly, the 2-imino-1,3-thiazolines are available in many biologically active compounds with antimicrobial, anticancer, anti-inflammatory, antihistaminic, antihypertensive, hypnotic, and anticonvulsant activities.6-13 In addition, they were applied for the identification of human cells with positive myeloperoxidase reactivity.14 For example 4-methyl-3-H-thiazoline derivative, PS-028, is a potent and selective GPIIb/IIIa receptor antagonist (Fig. 1).15-16 Also, KHG22394 containing 2-imino-1,3-thiazoline moiety is known as a melanin production inhibitor in a dose-dependent manner while not directly inhibit tyrosinase as a rate-limiting melanogenic enzyme and also applied for the production of skin whitening cream (Fig. 1).17 Another example with thiazoline core is Pifithrin, which is widely used as a p53 transcription inhibitor in cells and could restrict cellular apoptosis (Fig. 1).18-19 Furthermore, thiazolines have found applications as acaricides, insecticides, and plant growth regulators in agriculture.20-21
Nitroepoxides, which can be simply prepared from nitroalkenes by epoxidation reaction with H2O2/NaOH,22 are efficient intermediates in synthetic organic chemistry and were applied extensively as synthons of vicinal double electrophilic compounds such as α-diones and α-haloketones for the synthesis of valuable heterocyclic compunds.23 Although the synthesis of nitroepoxides and their ring opening with heteroatom-centered nucleophiles such as sodium phenoxides, sodium thiophenolates, and amines came back to around 50 years ago,24 but research on these compounds was accelerated in recent 15 years. Diversities of mono nucleophiles such as potassium xanthates, dithiocarbamic acids, sodium aryl sulfonates and sodium bisulfite were added to nitroepoxides to obtain the corresponding α-heterosubstituted ketones.23,25 In addition, bis-nucleophiles such as N-alkyl(thio)ethanolamine,26 amidines,27 diamines,28 S-alkyl dithiocarbamates23 and etc.29-31 have been utilized in the reaction with nitroepoxides for the synthesis of valuable heterocyclic compounds including imidazoles, 1,3-thiazoles, benzodiazepines, thiazoline-2-thiones, and pyrazines.
Multicomponent reactions (MCRs) provide simple access to complex molecules in a one-pot and have several advantages such as generation of several bonds in a single operation, avoiding the need for isolation and purification of reaction intermediates, saving in time, materials, solvents and energy.32-35 For this purpose, multicomponent reaction of isothiocyanates with amines in the presence of an electrophile is an efficient strategy for the synthesis of 2-imino-1,3-thiazolines. In this context, Yavari et al. developed a synthetic route for the synthesis of functionalized 2-imino-1,3-thiazoles using tetramethylguanidine, isothiocyanates, and 2-chloro-1,3-dicarbonyls (Scheme 1a).36 Meshram and co-workers investigated the one-pot three-component reaction of amines, phenyl isothiocyanates and β-nitroacrylates in [Hbim]BF4 ionic liquid (Scheme 1b).37 Furthermore, Raja et al., reported the reaction of aryl isothiocyanates, phenacyl bromides, and aryl amines in ethanol as green reaction media in 2016 (Scheme 1c).38 Chen and coworkers described the synthesis of 2-imino-1,3-thiazolidines and 2-imino-1,3-thiazolines through the reaction of ionic liquid attached 2-aminobenzimidazoles with isothiocyanates and 1,2-dichloroethane, followed by ionic cleavage with methanolysis reaction and oxidation with Mn(OAc)3 (Scheme 1d).39 In 2017, a one-pot three-component route for the synthesis of 2-aminothiazoles was developed by Guo et al. via the reaction of nitroepoxides with cyanamide and sodium sulfide. The scope of this reaction is limited to the use of nitroepoxides and other components cannot be changed (Scheme 1e).40 Beside multicomponent reactions, condensation reaction of N,Nʹ–disubstituted thiourea with α-haloketones and ring transformation of 2-(thiocyanomethyl) aziridines were also developed for the synthesis of 2-imino-1,3-thiazolines.41-44