Reaction of aryl-substituted azidopyrimidines with 1,3-dicarbonyl compounds

Steering the azido–tetrazole equilibrium of 4-azidopyrimidines via substituent variation – implications for drug design and azide–alkyne cycloadditions

“…For pyrimidines, especially 2-azidopyrimidines, the impact of the tautomerization on CuACC has not been investigated, yet. Only a few reports about the transformation of 2-azidopyrimidines 19 and 4-azidopyrimidines [20][21][22] into the corresponding triazoles have been published to date. However, in the aforementioned studies usage of Huisgen conditions (high temperature, no catalyst) resulting in a mixture of 1,4-and 1,5-disubstituted regioisomers (for terminal alkynes) or trisubstituted triazoles (for internal alkynes) is described.…”

“…7 By the linkage of the azide group at the 2, 4 and/or 6 position of pyrimidines, a phenomenon which is referred to as azido-tetrazole equilibrium, can be observed. [8][9][10][11][12][13][14] This constitutional isomerism is characterized by a ring closure of the azide with ortho-nitrogen of the pyrimidine core, resulting in the corresponding tetrazole (Scheme 1) and has drawn enormous attention of NMR-and IR-analysts, [8][9][10][11][12][13][14][15][16][17][18] synthetic chemists, [17][18][19][20][21][22][23][24][25] researchers in drug discovery, [26][27][28] and scientists from the field of computational chemistry. [29][30][31] In 1979, Könnecke et al provided a detailed analysis of substituent-dependent effects on this valence tautomerism and suggested that besides solvent and temperature, electronic as well as steric effects should be considered when investigating the position of the equilibrium.…”

Synthesis of Triazoles via Regioselective Reactions of Aryl Azides with ­Cyanoacetyl Pyrroles and Indoles

“…In such reactions, high regioselectivities were obtained with the exception of reactions of azides with unsymmetrical 1,3-diketones. For example, in the reaction of benzyl azides or azidopyrimidines with benzoylacetone 15,16 mixtures of two regioisomers were obtained as a result of attack of the azido nitrogen on either one of the two carbonyl groups (Scheme 1). The different nature of the substituents on benzoylacetone (Me and Ph) does not allow the regioselectivity to be predicted.…”

Azido-1,2,5-oxadiazoles in reactions with 1,3-dicarbonyl compounds

“…It is well known that aromatic azides can form 1,2,3-triazoles by cycloaddition to not only acetylenes or activated olefins but also compounds containing active CH 2 groups, such as 1,3-dicarbonyl compounds 3 [5][6][7][8][9][10][11] (Scheme 2). The position of the RCO group depends on the reaction mechanism.…”

“…The position of the RCO group depends on the reaction mechanism. 7,8,12,13 Triazoles are not always the only products of the above reaction. Amines, diazo compounds, etc., can be formed depending on the nature of the azide and the carbonyl component and on reaction conditions.…”