Aminoazoles 1,3-binucleophiles

In our review we present general and specific examples of all these three types of MCRs, which involve aminoazoles as 1,3-binucleophile reagents. In the following sub-chapters, the most part of published original articles and selected patents in this topic will be observed and discussed. 

In some cases, the question of positional and regioselectivity arises for MCR based on aminoazole. Regioselectivity problem concerning the presence of nonequivalent reaction centers in 1,3-binucleophile molecule is more specific for... 

As it has been already mentioned in the Introduction, aminoazoles besides the role of 1,3-binucleophiles can take part in the MCRs as 1,1-binucleophiles with participation of exclusively exocyclic NH2-group. Usual products of such multi-component interaction are five-membered heterocycles having azole ring as a substituent. 

More than a third part of all the described principal syntheses of pyrimidines bearing fluorinated alkyl at C-4 atom commences from fluorinated p-dicarbonyl compounds 699. The chemistry of these bis-electrophiles was reviewed recently [411, 412] therefore, their preparation is not discussed herein. This synthesis of pyrimidines is fairly general (Table 34) it allows for introducing aliphatic, alicyclic and aromatic p-diketones (Entries 1-10), p-ketoesters (Entries 11-16), and cyclic P-ketoamides (Entry 17). Presence of some functional groups, such as additional ester moiety (Entry 15), is more or less tolerated, whereas increasing steric hindrance results in lowered yields of the products (Entry 10). A scope of conunon NCN binucleophiles include amidines (Entries 1, 11, 12, 17), (thio)urea and its derivatives (Entries 2-4), guanidines (Entries 5,16) and biguanides (Entry 6). Electron-rich amino heterocycles e.g. aminoazoles and even 2,6-diaminopyridine) are excellent NCN binucleophiles for the principal synthesis of fused pyrimidine derivatives (Entries 7-10, 13-15). 

In case of non-symmetrical binucleophiles, the reaction with 699 is regioselec-tive (although not always 100 %). Normally, it should start with attack of more nucleophilic nitrogen atom of the nucleophile at the fluoroalkyl-substituted carbonyl group of the electrophile (see, for example. Table 34, Entries 4 and 12). Nevertheless, the available data, reported mainly for the reactions of aminoazoles. 

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