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. 2021 Aug 4;26(16):4719.
doi: 10.3390/molecules26164719.

Oxidative Aromatization of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines: Synthetic Possibilities and Limitations, Mechanism of Destruction, and the Theoretical and Experimental Substantiation

Daniil N Lyapustin  1 , Evgeny N Ulomsky  1   2 , Ilya A Balyakin  3   4 , Alexander V Shchepochkin  2 , Vladimir L Rusinov  1   2 , Oleg N Chupakhin  1   2
Affiliations

Oxidative Aromatization of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines: Synthetic Possibilities and Limitations, Mechanism of Destruction, and the Theoretical and Experimental Substantiation

Daniil N Lyapustin et al. Molecules. .

Abstract

The reaction tolerance of the multicomponent process between 3-aminoazoles, 1-morpholino-2-nitroalkenes, and aldehydes was studied. The main patterns of this reaction have been established. Conditions for the oxidation of 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines were selected. Previous claims that the 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines could not be aromatised have now been refuted. Compounds with an electron-donor substituent at position seven undergo decomposition during oxidation. The phenomenon was explained based on experimental data, electro-chemical experiment, and quantum-chemical calculation. The mechanism of oxidative degradation has been proposed.

Keywords: azolo[1,5-a]pyrimidines; multicomponent reactions; nitro compounds; nitro-synthons; oxidation; oxidative destruction; synthesis of heterocycles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of biologically active azolo[1,5-a]pyrimidines.
Scheme 1
Scheme 1
Current methods for the synthesis of 4,7-dihydroazolo[1,5-a]pyrimidines.
Scheme 2
Scheme 2
Preparation of 4,7-dihydro-6-nitro-5-methyl-7-phenylazolo[1,5-a]pyrimidines.
Scheme 3
Scheme 3
Preparation of 6-nitro-5-methyl-7-phenylazolo[1,5-a]pyrimidines.
Scheme 4
Scheme 4
Preparation of 4,7-dihydro-6-nitro-7-phenyl-5-R-pyrazolo[1,5-a]pyrimidines 6 and 4,7-dihydro-6-nitro-7-phenyl-5-R-pyrazolo[1,5-a]pyrimidines 7.
Scheme 5
Scheme 5
Preparation of 4,7-dihydro-6-nitro-5-methyl-7-R-azolo[1,5-a]pyrimidines 8.
Scheme 6
Scheme 6
Preparation of 6-nitro-5-methyl-7-R-azolo[1,5-a]pyrimidines 9.
Scheme 7
Scheme 7
Oxidation of 6-nitro-5-methyl-7-(anthracen-9-yl)azolo[1,5-a]pyrimidine 8e.
Figure 2
Figure 2
Visualization of HOMO for compounds 8b and 8e obtained in PBE0 approximation.
Figure 3
Figure 3
Cyclic voltammogram of 8b (blue) and 8e (red), 5 × 10−3 M.
Scheme 8
Scheme 8
Plausible mechanism of oxidation of 6-nitro-5-methyl-7-R-azolo[1,5-a]pyrimidines 8.
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