Chapter II SN(ANRORC) Reactions in Azines, Containing an “Outside” Leaving Group

The Synthesis and Biological Applications of the 1,2,3-Dithiazole Scaffold

“…The inhibition was also reversed by addition of dithiothreitol (DTE), indicating the reaction with protein Cys formed adducts, indicating that the reaction was likely going via an ANRORC-style rearrangement. Modelling, including molecular and quantum mechanical studies (MM and QM, respectively) and Frontier Orbital Theory (FOT) on 1,2,3-dithiazole models showed pathway (ii) was more likely, which is also supported by previous reports on the 1,2,3-dithiazole ( Figure 32 ) [ 38 , 39 , 40 ].…”

“…An example of this is where the N -Aryl-5 H -1,2,3-dithiazol-5-imines 4 react with an excess of dialkylamines to give 4-aminodithiazoles 9 in variable yields ( Scheme 7 ). The reaction was found to proceed via an ANRORC-style mechanism [ 38 , 39 ] involving ring opening by nucleophilic attack on the S2 position to yield disulfides 10 and subsequent recyclization after amine addition on the cyano group [ 40 ]. In another report by Koutentis et al [ 14 ], DABCO was reacted with neutral 5 H -1,2,3-dithiazoles 4 – 6 to give N -(2-chloroethyl)piperazines 11 in good yields ( Scheme 7 ).…”

“…The zinc ion is then ejected to form a stable complex, with or without adducts ( Figure 28 ). In addition to the literature rearrangement examples [ 38 , 39 , 40 ], we also provided extensive computational modelling to support the mechanistic rationale provided.…”

The Conversion of 5,5′-Bi(1,2,3-dithiazolylidenes) into Isothiazolo[5,4-d]isothiazoles

“…Tentatively, we propose the thiophile-mediated reaction (Table 2) proceeded via an ANRORC style reaction pathway [32,33,34], where the thiophile attacks either the dithiazole S1 or S2 sulfurs to generate a ring opened species that then collapses to give the isothiazole ring system (Scheme 5). At this stage, it is not possible to give an accurate mechanism, as several possibilities exist.…”

“…The chemistry of 1,2,3-dithiazoles has been extensively reviewed [25,26,27] and 4-chloro-5 H -1,2,3-dithiazoles undergo both thermal [28,29,30,31] and ANRORC-mediated [32,33,34] ring transformations to afford various heterocycles, including both thiazoles [28,29,30,31,35,36,37,38] and isothiazoles [36,39,40,41,42]. As such, we proposed that 5,5′-bi(1,2,3-dithiazolylidenes) 11 could be similarly converted into isothiazolo[5,4- d ]isothiazoles 8 providing a new route to this rare biheterole.…”