Keywords
tautomerism
electrophilic substitution
privileged scaffold.
How to Cite
Abstract
2-Amino-4,6-dihydroxypyrimidine (CAS 56-09-7) represents an indispensable heterocyclic building block widely exploited in organic synthesis, agrochemicals and pharmaceutical design. Although the baseline molecule features modest direct biological efficacy due to its highly stable, neutral tautomeric states, its unique spatial arrangement of three strong electron-donating groups unlocks exceptional reactivity. This review systematically maps the core chemical and physical properties of the molecule, addresses its dynamic keto-enol (lactam- lactim) structural isomerism, classifies its nucleophilic and electrophilic reaction centers and details the vast spectrum of biological activities—including antiviral, anticancer, anti- inflammatory and antimicrobial profiles – unlocked upon derivative functionalization.References
1. Lagoja I. M. Pyrimidine as constituent of natural biologically active compounds //Chemistry & biodiversity. – 2005. – Т. 2. – №. 1. – С. 1-50.
2. Jansa P. et al. 5-Substituted 2-amino-4, 6-dihydroxypyrimidines and 2-amino-4, 6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production //Medicinal Chemistry Research. – 2014. – Т. 23. – №. 10. – С. 4482-4490.
3. Hall V. M., Bertke J. A., Swift J. A. Two tautomeric forms of 2-amino-5, 6-dimethylpyrimidin-4-one //Crystal Structure Communications. – 2016. – Т. 72. – №. 6. – С. 460-464.
4. ChemicalBook Database (2026). Physicochemical Properties of 2-Amino-4,6-dihydroxypyrimidine (CAS 56-09-7).
5. Stenutz Chemistry Database. Tables for Chemistry: Isomers of 2-amino-4,6-dihydroxypyrimidine.
6. BenchChem Technical Support Team. Tautomerism and Stability of 2-Ethoxy-4,6- dihydroxypyrimidine: An In-depth Technical Guide. Foundational & Exploratory. 2026.
7. Brown D. J. The Pyrimidines, Volume 16. – John Wiley & Sons, 2009. – Т. 16.
8. Wang T. et al. Salts, cocrystals, and ionic cocrystals of a “simple” tautomeric compound //Crystal Growth & Design. – 2018. – Т. 18. – №. 11. – С. 6973-6983.
9. Vu T. Q. et al. Spectroscopic study of the basicity of 4, 6-dihydroxypyrimidine derivatives //ACS omega. – 2021. – Т. 6. – №. 22. – С. 14154-14163.
10. Vorbrüggen H., Ruh-Pohlenz C. Handbook of nucleoside synthesis. – John Wiley & Sons, 2001.
11. Baraldi P. G. et al. New strategies for the synthesis of A3 adenosine receptor antagonists //Bioorganic & medicinal chemistry. – 2003. – Т. 11. – №. 19. – С. 4161-4169.
12. Patel P. R., Ramalingan C., Park Y. T. Synthesis and antimicrobial evaluation of guanylsulfonamides //Bioorganic & medicinal chemistry letters. – 2007. – Т. 17. – №. 23. – С. 6610-6614.
13. Rostom S. A. F., Ashour H. M. A., Abd El Razik H. A. Synthesis and biological evaluation of some novel polysubstituted pyrimidine derivatives as potential antimicrobial and anticancer agents //Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry. – 2009. – Т. 342. – №. 5. – С. 299-310.
14. Reichardt C. Vilsmeier–Haack–Arnold formylations of aliphatic substrates with N‐chloromethylene‐N, N‐dimethylammonium salts //Journal für praktische Chemie. – 1999. – Т. 341. – №. 7. – С. 609-615.
15. Dolakova P. et al. Acyclic nucleoside bisphosphonates: Synthesis and properties of chiral 2-amino-4, 6-bis [(phosphonomethoxy) alkoxy] pyrimidines //European journal of medicinal chemistry. – 2009. – Т. 44. – №. 6. – С. 2408-2424.
16. Holy A. et al. 6-[2-(Phosphonomethoxy) alkoxy] pyrimidines with antiviral activity //Journal of Medicinal Chemistry. – 2002. – Т. 45. – №. 9. – С. 1918-1929.
17. Trilleras J., Pérez-Gamboa A., Quiroga J. SNAr Reactions on 2-Amino-4, 6-dichloropyrimidine-5-carbaldehyde //Molbank. – 2022. – Т. 2022. – №. 3. – С. M1426.
18. Quiroga, J.; Trilleras, J.; Insuasty, B.; Abonia, R.; Nogueras, M.; Marchal, A.; Cobo, J. Microwave-assisted synthesis of pyrazolo[3,4-d]pyrimidines from 2-amino-4,6-dichloropyrimidine-5-carbaldehyde under solvent-free conditions. Tetrahedron Lett. 2008, 49, 3257–3259.
19.
10. Quiroga J. et al. Microwave-assisted synthesis of pyrazolo [3, 4-d] pyrimidines from 2-amino-4, 6-dichloropyrimidine-5-carbaldehyde under solvent-free conditions //Tetrahedron Letters. – 2008. – Т. 49. – №. 20. – С. 3257-3259.
20. Cobo J. et al. N6-Substituted 2-amino-4-chloro-5-formylpyrimidines: puckered versus planar pyrimidine rings, and hydrogen-bonded aggregation in zero, one, two and three dimensions //Structural Science. – 2008. – Т. 64. – №. 5. – С. 596-609.
21. Trilleras J., Polo-Cuadrado E., Quiroga J. (E)-Methyl 3-(2-amino-4-chloro-6-morpholinopyrimidin-5-yl) acrylate //Molbank. – 2026. – Т. 2026. – №. 1. – С. M2141.
22. Jadhav M. et al. Synthetic strategies of pyrimidine-based scaffolds as aurora kinase and polo-like kinase inhibitors. 2021; 26 (17): 5170 //DOI: á10. – Т. 3390.
23. Bayramoğlu D., Kurtay G., Güllü M. Ultrasound-assisted rapid synthesis of 2-aminopyrimidine and barbituric acid derivatives //Synthetic Communications. – 2020. – Т. 50. – №. 5. – С. 649-658.
24. Sakhare D. T., Shankarwar S. G., Shankarwar A. G. Synthesis, characterization and antimicrobial activities of some Mn (II) and Fe (III) complexes of biologically active bidentate ligands. – 2015. –7(6):C.198-204.
25. Sakhare d. T. Synthesis, characterization and biological activity of substituted aminopyrimidine schiff base ligand and their complexes of Cu (II) and Mn (II) //International Journal of Chemistry Research. – 2025. – С. 1-6.
26. Marcialis M. A. et al. In vitro and in vivo inhibitory action of 2-amino-4, 6-dichloropyrimidine on polio and herpes virus //Experientia. – 1974. – Т. 30. – №. 11. – С. 1272-1273.
27. Guzik T., Korbut R., Adamek-Guzik T. Nitric oxide and superoxide in inflammation //J physiol pharmacol. – 2003. – Т. 54. – №. 4. – С. 469-487.
28. Mughal E. U. et al. Design and synthesis of 2-amino-4, 6-diarylpyrimidine derivatives as potent α-glucosidase and α-amylase inhibitors: structure–activity relationship, in vitro, QSAR, molecular docking, MD simulations and drug-likeness studies //Journal of Biomolecular Structure and Dynamics. – 2024. – Т. 42. – №. 1. – С. 244-260.
29. Saleh N. M. et al. Novel Anticancer Fused Pyrazole Derivatives as EGFR and VEGFR-2 Dual TK Inhibitors, Front. – 2020.
30. Borea P. A. et al. Pharmacology of adenosine receptors: the state of the art //Physiological reviews. – 2018.
31. Gelmboldt V. O. et al. Synthesis, structure, and anticaries activity of 2-amino-4, 6-dihydroxypyrimidinium hexafluorosilicate //Pharmaceutical Chemistry Journal. – 2018. – Т. 52. – №. 7. – С. 606-610.
32. Gelmboldt V. O., Kravtsov V. C., Fonari M. S. Ammonium hexafluoridosilicates: Synthesis, structures, properties, applications //Journal of Fluorine Chemistry. – 2019. – Т. 221. – С. 91-102.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Zayniddinovna Azimova Gulmira, Zukhra Zafar qizi Akbarkhanova (Author)