A diversity of alkylation/acylation products of uracil and its derivatives: Synthesis and a structural study
tert-Butyl dicarbonate (Boc2O) and ethyl iodide (EtI) reactions with uracil (U), thymine (T) and 6-methyluracil (6-MU) were performed following routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives. Parallel quantum mechanical DFT calculations supported the experimental findings.
Michalak, Olga,Cmoch, Piotr,Krzeczyński, Piotr,Cybulski, Marcin,Le?, Andrzej
p. 354 - 362
(2019/01/10)
HSAB-driven chemoselective N1-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives
The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1H)-pyrimidinones 1-3 undergo highly chemoselective N1-methylation or ethylation when treated with methyl- or ethylsulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O2-alkylation. Potassium salts of the same bases in DMF undergo prevalent O2-attack. Under the same conditions, a similar but less chemoselective behaviour is observed in alkylation of thymine and uracil, where some N3-attack occurs. This can be rationalised in terms of the HSAB principle.
Gambacorta, Augusto,Tofani, Daniela,Loreto, Maria Antonietta,Gasperi, Tecla,Bernini, Roberta
p. 6848 - 6854
(2007/10/03)
HSAB driven chemoselectivity in alkylation of uracil derivatives. A high yielding preparation of 3-alkylated and unsymmetrically 1,3-dialkylated uracils
A qualitative hardness scale (N134) has been found for the conjugated bases of 2-methoxy-4(3H)-pyrimidinones 1-3 and applied to high yielding chemoselective N3 methylation, ethylation and benzylation reactions. Removal of the 2-methoxy group followed by a second alkylation affords unsymmetrically 1,3-disubstituted uracils.