Antioxidant properties of some 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-2(1H)-ones (-thiones) and their derivatives

Article abstract of DOI:10.1134/S1070427210020205

Inhibiting properties of some synthesized 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-2(1H)-ones (-thiones) and their derivatives in model reactions were studied.

Full text of DOI:10.1134/S1070427210020205

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2010, Vol. 83, No. 2, pp. 293−296. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.V. Zamanova, M.M. Kurbanova, I.A. Rzaeva, V.M. Farzaliev, M.A. Allakhverdiev, 2010, published in Zhurnal Prikladnoi Khimii,
2010, Vol. 83, No. 2, pp. 294−297.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Antioxidant Properties of Some 5-Ethoxycarbonyl-Substituted
3,4-Dihydropyrimidin-2(1Н)-ones (-thiones)
and Their Derivatives
A. V. Zamanovaa, M. M. Kurbanovab, I. A. Rzaevaa, V. M. Farzalieva, and M. A. Allakhverdievb
a Kuliev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
b Baku State University, Baku, Azerbaijan
Abstract—Inhibiting properties of some synthesized 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-2(1H)-
ones (-thiones) and their derivatives in model reactions were studied.
DOI: 10.1134/S1070427210020205
It is known that 3,4-dihydropyrimidin-2(1Н)-ones
(-thiones) and their derivatives exhibit a wide spectrum
of biological activity. In addition, they are powerful
calcium channel blockers, antihypertensive drugs, and
neutopeptide antagonists [1].
In this study we examined the antioxidant properties of
some ethoxycarbonyl-substituted 3,4-dihydropyrimidin-
2(1H)-ones (-thiones) and their derivatives I–V. Com-
pounds I–III were synthesized by ternary condensation
[2]:
IV
2-(2',3'-Epoxypropylthio)-6-methyl-4-phenyl-3,4-
dihydropyrimidine-5-carboxylate V was synthesized by
the reaction of 5-exthoxycarbonyl-6-methyl-4-phenyl-
3,4-dihydropyrimidin-2(1Н)-thione with epichlorohydrin
[3]:
where Х = О, R = СН3 (I); X = O, R = С6Н5 (II); Х =
S, R = С6Н5 (III).
3-(2',3'-Epoxypropyl)-6-methyl-4-phenyl-2-oxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate IV was
synthesized by the reaction of 5-exthoxycarbonyl-6-
methyl-4-phenyl-3,4-dihydropyrimidin-2(1Н)-one with
V
epichlorohydrin [3]:
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ZAMANOVA et al.
Table 1. Physicochemical characteristics of I–V
The structures of the compounds synthesized were
confirmed by IR and 1Н and 13С NMR spectroscopy, and
the purity, by TLC. The physicochemical characteristics
of the compounds synthesized are given in Table 1.
the quantity k7 was determined:
tan k2[RH] Wi
=
,
k7
f [InH] 0
To evaluate the antioxidant activity of I, IV, and V
in elementary steps of cumene oxidation, we studied the
reactions of these compounds with cumylperoxy radicals
(CPRs) and cumyl hydroperoxide (CHP).
where k2 is the rate constant of chain initiation [4, 5],
equal to 1.51 l mol–1 s; [RH] = 7.17 M.
High antioxidant activity of I, IV, and V was also
confirmed in experiments on cumene autooxidation at
110°С, and the kinetic parameters of the reactions were
determined (Fig. 2).
The capability of I, IV, and V to terminate oxidation
chains by the reaction with CPRs was evaluated using
as example the cumene oxidation at 60°С, initiated by
azobis(isobutyronitrile) (AIBN) taken in a concentration
of 2 × 10–2 M. We found that compounds I, IV, and
V actively terminate oxidation chains by reacting with
CPRs (Fig. 1).
As seen from Table 2, the coefficients f for I, IV, and
V vary from 0.5 to 1.58, and the constant of the reaction
of the inhibitors with CPRs, k7, varies from 2.01 × 104 to
2.60 × 104 l mol–1 s–1. The products formed in reactions
From the duration of the induction period τind we
calculated the stoichiometric coefficient of the inhibition
f, equal to the number of oxidation chains terminated on
one inhibitor molecule and its transformation products:
ind Wi
f =
f =
,
[InH] 0
where Wi is the initiation rate and [InH]0 is the initial
inhibitor concentration.
From the kinetics of oxygen uptake we calculated
the rate constants of the reactions of the compounds in
question with CPRs, k7 [4, 5]. To this end, the kinetic
curves of the oxygen uptake were transformed from the
[O2]–τ coordinates to the [O2]–1–τ–1 coordinates, and from
the slope of the straight line [5, 6]
τ, min
Fig. 1. Kinetic curves of initiated oxidation of cumene in the
presence of I, IV, and V. Т = 60°C, [AIBN] = 2 × 10–2 M,
[InH] = 5 × 10–4 M. (VO2) Oxygen volume and (τ) time; the
same for Fig. 2. Inhibitor: (0) none, (1) I, (2) IV, and (3) V;
the same for Fig. 2.
f k7[InH] 0
,
tan =
k2[RH] Wi
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ANTIOXIDANT PROPERTIES OF 5-ETHOXYCARBONYL...
295
τ, min
Fig. 3. Kinetic curve of CHP decomposition in the presence
of V. Т = 110°С, [CHP]0 = 0.38 M, [InH]0 = 1 × 10–4 M. (τ)
Time.
τ, min
Fig. 2. Kinetic curves of cumene autooxidation in the presence
of I, IV, and V. Т = 110°С.
where [RООH]0 and [RООH]” are the initial and final
CHP concentrations, respectively, and [In]0 is the initial
inhibitor concentration.
of I, IV, and V with CPRs exhibit certain inhibiting
effect: The oxidation rate after the induction period
is somewhat lower than in the case of the uninhibited
oxidation (Fig. 1).
Experiments showed that one molecule of I, IV,
and V can decompose up to several tens thousands
(20000–25000) CHP molecules. It can be concluded that
the compounds under consideration exert a combined
inhibiting effect, terminating oxidation chains in reaction
with CPRs and catalytically decomposing CHP.
The reactions of I, IV, and V with CHP were
performed in chlorobenzene under nitrogen at 110°С.
We found that, for all the compounds studied (Fig. 3),
the kinetic curve of CHP decomposition under the
action of compounds I, IV, and V is S-shaped, which is
characteristic of an autocatalytic process. The reaction
starts with a certain induction period when the CHP
consumption is insignificant, which is followed by
rapid catalytic decomposition of CHP, and then the
reaction rate decreases owing to a decrease in the CHP
concentration.
EXPERIMENTAL
The purity of the compounds prepared and the
reaction progress were monitored by TLC on Silufol
UV-254 plates, with 2-propanol–hexane mixture (1 : 1)
as eluent.
3,4-Dihydropyrimidin-2(1Н)-ones (-thiones) were
synthesized by the published procedure [2]. A round-
bottomed flask equipped with a reflux condenser and
a power-driven stirrer was charged with an aldehyde
(1.25 mol), ethyl acetoacetate (1.90 mol), urea or thiourea
(1.25 mol), CCl3COОH (25 mg), and 95% ethanol
Apparently, the inhibitor first reacts with CHP, and
then the resulting transformation product catalytically
decomposes CHP. To determine the reaction stoichiometry,
CHP was taken in an excess.
The catalytic factor is ν = [RООH]0 – [RООH]∞/[In]0,
Table 2. Kinetic parameters of reactions of I, IV, and V with cumylperoxy radicals, k7 and ѓ (60°C, [AIBN] = 2 × 10–2 M), and
of cumyl hydroperoxide decomposition, k and ν (110°С)
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CONCLUSIONS
(10 ml). The reaction mixture was stirred for 2–4 h.
The reaction progress was monitored by TLC. After the
reaction completion, the mixture was cooled to room
temperature, and the crystalline product was filtered
off, washed with ethanol, dried, and recrystallized from
aqueous ethanol (1 : 3).
(1) The synthesized 5-ethoxycarbonyl-substituted
3,4-dihydropyrimidin-2(1Н)-ones (-thiones) and their
derivatives exhibit high antioxidant ability.
(2) They efficiently inhibit cumene oxidation and
decompose the oxidation product, cumyl hydroperoxide.
General procedure for preparing IV and V [3].
A mixture of 0.1 mol of epichlorohydrin and 0.01 mol
of 5-ethoxycarbonyl-substituted 3,4-dihydropyrimidin-
2(1Н)-one (-thione) I–III in 15 ml of dimethylformamide
was refluxed for 3–4 h. After that, the reaction mixture
was allowed to stand at room temperature and then
cooled to 0°С. The precipitated crystals were filtered
off, washed with cold ethanol, and recrystallized from
ethanol. Cumyl hydroperoxide was purified according
to [6] and then distilled.
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the range (1–5) × 10–4 M.
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all the experiments was constant, 2 × 10–2 M, and the
concentration of I–V was (1–5) × 10–4 M.
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