ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 4, pp. 750–752. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Obshchei Khimii, 2020, Vol. 90, No. 4, pp. 642–644.
LETTERS
TO THE EDITOR
Some Features of the Reaction of 6-Methyl-2S-substituted
Pyrimidin-4-ols with the Vilsmeier–Haack Reagent
E. S. Ofitserovaa,*, A. A. Shklyarenkoa, and I. P. Yakovleva
a St. Petersburg Chemical and Pharmaceutical University of the Ministry of Health of Russia, St. Petersburg, 197376 Russia
Received November 1, 2019; revised November 1, 2019; accepted December 21, 2019
Abstract—Formylation of 6-methyl-2S-substituted pyrimidin-4-ols under the conditions of the Vilsmeier–Haack
reaction leads to the formation of nucleophilic substitution products of the hydroxyl group. The formation of the
expected formylation products does not occur.
Keywords: formylation, Vilsmeier–Haack reagent, 6-methyl-2S-substituted pyrimidin-4-ol
DOI: 10.1134/S1070363220040301
The carbonyl group introduced into the organic
compound molecule is a convenient tool for constructing
annelated heterocyclic structures [1] exhibiting a wide
range of pharmacological properties [2]. The most
acceptable way to obtain aldehydes is formylation
according to Reimer–Tiemann or Vilsmeier–Haack
reaction.
substitution of the hydroxy group in the molecule of the
starting 6-methyl-2S-substituted pyrimidin-4-ol 3a–3c
occurs, and the resulting chlorine derivatives 4a–4c does
not enter into the formylation reaction.
General procedure for S-alkylation of 4-hydroxy-
6-methylpyrimidine-2(1H)-thione (2). A mixture of
5.0 g (35.2 mmol) of 4-hydroxy-6-methylpyrimidine-
2(1H)-thione 2 and 0.8 g (35.2 mmol) of sodium
hydroxide dissolved in 10 mL of water was stirred until
the precipitate was completely dissolved, then a solution
of an alkylating agent (42.24 mmol) in 10 mLof dioxane
was added. The resulting emulsion was stirred at room
temperature for 12 h. The precipitate was filtered off
and dried.
The use of theVilsmeier–Haack reagent (POCl3–DMF)
for the formylation of most aromatic and heteroaromatic
compounds has been sufficiently studied and described
in [3]. Polyoxypyrimidine derivatives occupy a special
place as substrates for carrying out the formylation
reaction. Thus, during the formation of 2S-substituted
derivatives of thiobarbituric acids [4, 5], simultaneously
with the formation of the target compound, parallel
nucleophilic substitution of one or more hydroxy groups
of the pyrimidine ring occurs. Compounds synthesized
in this way are interesting synthons for obtaining new
polyheterocyclic structures [6].
6-Methyl-2-(methylthio)pyrimidine-4-ol (3a). Yield
1
80%, white powder, mp 180–182°С (subl.). Н NMR
spectrum (DMSO-d6), δ, ppm: 2.16 s (3Н, СН3), 2.46 s
(3Н, SСН3), 5.96 s (1Н, pyrimidine), 12.44 br. s (1H, ОН).
Found, %: C 46.11; H 5.12; N 17.91; O 10.23. C6H8N2OS.
Calculated, %: C 46.13; H 5.16; N 17.93; O 10.24.
Of particular interest are the 6-methyl-2S-substituted
pyrimidin-4-oles 3a–3c obtained by the reaction of
thiourea 1 with acetoacetic ester [7] followed by
alkylation at the sulfur atom (Scheme 1). As in the case
of 2S-substituted thiobarbituric acid, the formyl group
was introduced under the conditions of the Vilsmeier–
Haack reaction with an excess of phosphorus oxychloride
[4, 5]. It was found that, regardless of the amount of
excess phosphorus oxychloride, only the nucleophilic
6-Methyl-2-[(1-naphthylmethyl)thio]pyrimidine-4-
ol (3b). Yield 75%, white powder, mp 200–202°С (subl.).
1Н NMR spectrum (DMSO-d6), δ, ppm: 2.27 s (3Н, СН3),
4.90 s (2Н, SСН2), 6.04 s (1Н, pyrimidine), 7.44–7.48 m
(1Н, НAr), 7.54–7.62 m (2Н, НAr), 7.67–7.69 m (1Н, НAr),
7.87–7.89m(1Н,НAr),7.95–7.97m(1Н,НAr),8.13–8.15m
(1Н, НAr), 12.51 br. s (1H, ОН). Found, %: C 68.03; H
750
Ofitserova, E. S.
