Synthesis of 2-(N-Benzoylimino)-N-(9,10-Dioxo-9,10-Dihydroanthracen-1-yl)Thiazoles

Abstract

N-Aroylthioureas hold a significant promise for the synthesis of such heterocycles as imidazolidine2-thiones [1, 2], 2-aroyliminothiazolines [3-5], 1,2,4-triazoles [6], 1,3-thiazines [7], and indeno[1,2-d][1,3]thiazepines [8]. Of particular interest are 2-iminothiazolines, which are characterized by a wide range of biological properties [9-11]. For example, the thiazol-2-imine fragment is a structural fragment in muscarinic agonists, as well as antifungal, hypolipidemic, antidiabetic, anti-inflammatory, analgesic, and anti-shistosomiasis compounds [5]. Thiazoline derivatives are also used as insecticides and plant growth regulators [5]. The reaction of N,N'-disubstituted thioureas with α-bromo ketones has been described in the literature [5, 12], and it provides access to various N-substituted 2-iminothiazoles. However, 2-iminothiazoles with 9,10-dioxo9,10-dihydroanthracenyl substituents at position 3 of the heterocycle remain hitherto unknown. The pronounced biological properties of anthraquinone derivatives [13-15] motivate the search for hybrid structures that include both anthraquinone and thiazole ring systems. Based on these considerations, we treated our previously described N-benzoyl-N'-(9,10-dioxo9,10-dihydroanthracen-1-yl)thioureas 1а-е [16] with in situ generated α-bromoacetone in the presence of triethylamine and obtained the 2-(N-benzoylimino)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thiazoles 2а-е in 48-68% yields. The formation of 2-(N-benzoyl)imine type thiazoles through a cyclocondensation with the participation of aminoanthracene nitrogen atom was in agreement with the recently described reactions of N-arylN'-aroylthioureas with α-halo ketones [4, 12, 13]. The Н NMR spectra of the compounds 2а-е contained thiazole H-5 proton singlets at 6.89-7.01 ppm and methyl group singlets at 1.97-2.04 ppm, besides the CH signals of the aromatic rings. The formation of a thiazole ring was also clearly confirmed by the С spectra containing the characteristic С-4 singlets at 106.1-107.2 ppm, С-5 singlets at 139.3-144.9 ppm, and С-2 singlets at 168.2-169.7 ppm. The C signals of the thiazole 4-СН3 substituent were found at 13.7-14.2 ppm, which was typical for 3-aryl-2-benzoylimino-4-methyl-1,3-thiazolines [4, 5]. Thus, we have prepared new 2-(N-benzoylimino)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thiazoles by a novel route, starting from N-benzoyl-N'-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thioureas.