Azines aminoazines

Azine approach. The fused pyrimidines can be synthesized in the same way as the pyridines, e.g. by the cyclization of vicinal aminothiocyanates (70JCS(C)2478>. Another useful method for aminoazines is the reaction with chlorocarbonylsulfenyl chloride, e.g. with the aminopyrimidine (440) (73LA1018). The reaction can be rationalized by initial acylation of the amino group which is then cyclized with formation of the 2(3//)-one (441). Another case is the reaction of the 6-aminouracil (442) with thionyl chloride (69JOC3285). The reaction is rationalized as an initial electrophilic substitution at the 5-position of the activated pyrimidine. Subsequently the chlorosulfinyl derivative (443) is cyclized to a thiazoline S-oxide which loses water to yield the thiazole. 

Fig. I. Plot of pK values of azine derivatives versus for azinyl groups. O, Acetylazines, DMSO 0, aminoazines, DMSO A, methylazines, DME.

Shaabani et al. reported a facile method for the synthesis of imidazo[ 1,2-a]azines by a one-pot three-component condensation of an aldehyde, a 2-aminoazine, and trimethylsilylcyanide, as an isocyanide equivalent, in the presence of l-n-butyl-3-methyUmidazolium bromide ([bmim][Br]) as a promoter under classical heating conditions in high yields with rather short reaction times (Fig. 12.16) [12]. 

In another study, Shaabani and Maleki described a multicomponent condensahon of aldehydes, 2-aminoazines, and TMSCN in the presence of [BMIM][Br] in a molar ratio of 1 1.4 (reactant/IL) under heating condition to afford 3-aminoimidazo[l,2-fl]azines 66-68 in good-to-significant yield (Scheme 26) [134]. The IL used was recycled and reused four times witii gradual decrease in product yield. In the absence of the IL, the reaction yielded only 5% of the product after heating at 80 °C for 3h. In molecular solvents, the reaction accomplished only in the presence of catalysts such as Sc(OTf)2, HCIO4, or AcOH at RT in 48h witii recorded yield of <65% [135]. 

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