Tautomerism characteristics of 4-pyrimidone

Figure 1. Structural formula of 4-pyrimidone

Pyrimidone is the name given to either of two heterocyclic compounds with the formula C4H4N2O: 2-pyrimidone and 4-pyrimidone. The compounds can also be called 2-hydroxypyrimidine or 4-hydroxypyrimidine respectively, based on a substituted pyrimidine, or 1, 3-diazine, ring. Here we will introduce 4-pyrimidinone, an important bioactive molecule, which has various biological activities such as anti-virus, anti-tumor, induction of interferon production and immune regulation.

Because the nucleic acid bases guanine, uracil and thymine all contain a 4-pyrimidone structure, people have carried out experimental and theoretical studies on 4-pyrimidone and its analogs. 4-pyrimidinone and its analogs can produce tautomerism due to the proton migration. In this regard, some people have used the semi-empirical quantum chemical MNDO method to calculate the relative stability of 4-pyrimidone tautomers in the gas phase. Some people have also theoretically studied the assignment of characteristic peaks of 4-pyrimidone infrared spectra in the gas phase using the methods HF/6-31G and MP2/6-31G. There are also researchers who have specifically studied the tautomerism mechanism of 4-pyrimidone. 4-Pyrimidinone is prone to tautomerization of keto and alcohol structures due to the instability of the carbonyl group in the molecule. Li et al. plotted the potential energy curves of different tautomers of 4-pyrimidone and calculated the total energy of the zero point energy of their tautomeric transition states, and analyzed that: A stable six-membered ring structure (the effect of hydrogen bonding) with a small covalent bond tension makes it easier to switch molecular structures. It is concluded that the isolated 4-pyrimidone and its analogs all have the 4-keto structure as the most stable structure, and the addition of water does not change the stability order. Intramolecular proton migration requires a large activation energy. In the process of water-assisted proton migration, hydrogen bonding plays a very important role. Its formation greatly reduces the activation energy of the reaction. At the same time, tension is also an important factor.

In addition, pyrimidone and triazinone can be tautomeric under certain conditions. The concept of heterocyclic tautomerisim is critical to the structure of DNA6. Scientists prove  that liquid-phase methylation of 2-methylthio-4-pyrimidone, 6- methyl-2- methylthio-4-pyrimidone  and 6-methyl-3-methylthio-1,2,4-triazine-5- one with MeOH over HY-Zeolite selectively gave 1-methyl-2-methylthio-4- pyrimidone, 1,6-dimethyl-2-methylthio-4-pyrimidone and 2,6-dimethyl-3- methylthio-1,24- triazine-5-one, respectively. Methyl iodide or dimethyl sulfate have been used as methylating agents for pyrimidines and 1,2,4-triazines. Alkylation of 2-thiouracil and 6-methyl-2-thiouracil with methyl iodide under basic conditions is known to lead.   

References

[1]Les A, Ortega—blake I. Theoretical study of tautomerism：2 and 4-oxoprimidine and some of their derivatives[J]. Int J Quantum Chem, 1985, 27: 567—572.
[2]Yi L, Shanhui H. 2-Ureido-4-Pyrimidone-Based Hydrogels with Multiple Responses[J]. ChemPhysChem. 2013,14(13).
[3] Lapinski L, Nowak M J, Les A, et a1. Comparison of ab initio HF/6-31G, HF/6-31++G and MP2/6-31G calculated infrared spectra of 4(3H)-pyrimidinone and 4-hydroxypyrimidine with matrix isolation spectra[J]. Vibrat Spectr, 1995, 8: 331— 342.
[4]Li Baozong. Theoretical Investigation on Tautomerism in 4(3H)-Pyrimidinone and its Analogues[J]. CHEMICAL RESEARCH, 2007, 18(1): 54-56.