Cyclic thioureas as cumene oxidation inhibitors

Article abstract of DOI:10.1134/S1070427210040245

Hexahydro-1,3,5-triazine-4-thiones were synthesized by ternary condensation of thiourea with various aldehydes and amines. The products were characterized by IR and NMR spectroscopy, and their inhibiting effect on cumene oxidation was examined.

Full text of DOI:10.1134/S1070427210040245

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2010, Vol. 83, No. 4, pp. 707−711. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.N. Garibov, I.A. Rzaeva, N.G. Shykhaliev, A.I. Kuliev, V.M. Farzaliev, M.A. Allakhverdiev, 2010, published in Zhurnal Prikladnoi
Khimii, 2010, Vol. 83, No. 4, pp. 655−659.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Cyclic Thioureas as Cumene Oxidation Inhibitors
E. N. Garibova, I. A. Rzaevaa, N. G. Shykhalievb, A. I. Kulieva, V. M. Farzalieva,
and M. A. Allakhverdieva
a Kuliev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
b Baku State University, Baku, Azerbaijan
Received August 4, 2009
Abstract—Hexahydro-1,3,5-triazine-4-thiones were synthesized by ternary condensation of thiourea with
various aldehydes and amines. The products were characterized by IR and NMR spectroscopy, and their
inhibiting effect on cumene oxidation was examined.
DOI: 10.1134/S1070427210040245
Thiourea and its derivatives are convenient starting
compounds for preparing various heterocyclic systems [1].
Also, N-substituted thioureas exhibit a wide spectrum
of physiological activity. Some of these compounds
show antitumor, antiviral, antibacterial, and therapeutic
activity [2]. The chemistry of heterocyclic compounds
synthesized from thiourea and its derivatives is one of
the most interesting and rapidly developing fields of the
modern organic chemistry. Such heterocycles are used
as pharmaceuticals, chemical agents for plant protection,
bioprotectors for fuels and lubricating oils, antioxidants,
fireproofing agents, and additives to polymeric materials
for imparting to them special properties [3–6]. Thietanyl
derivatives and other substituted thioureas show high
antioxidant activity [7, 8].
The physicochemical constants, yields, and other
parameters are given in Table 1.
The structure of the synthesized cyclic thioureas I–
1
VI was proved by IR and Н, 13С NMR spectroscopy,
and the purity, by elemental analysis and thin-layer
chromatography.
In the IR spectra of I–VI, the absorption band at
1215–1185 cm–1 corresponds to stretching vibrations of
the С=S bond. It should be noted that the С=S band, in
contrast to the С=О band, is not always readily revealed.
The С(S)N vibrations are observed at 1340–1245 cm–1
[11]. Generally the С(S)N stretching vibrations are
Scheme.
NH2
NH2
H
O
We synthesized cyclic thioureas by ternary
condensation of thiourea, various aldehydes, and
primary amines [7–10] and examined the correlation
between their structure and antioxidant properties (see
the scheme)
S
R + H2N
C
+ 2
C
R'
R
NH CH
With aqueous ammonia used in the ternary
condensation, the reaction is usually performed at room
temperature for 20–40 h. With amines, the reaction is
performed at 60–70°C for 3 h in benzene. The formation
of cyclic thioureas I–VI is monitored by thin-layer
chromatography. Cyclic thioureas I–VI are white finely
crystalline substances. They are readily soluble in
acetone, ethanol, and dimethyl sulfoxide.
S
C
NR',
_2H2O
NH CH
R
R = H, R' = CH3 (I); R = H, R' = CH2=CH–CH2 (II); R =
H, R' = (CH3)3C (III); R = H, R' = C6H5CH2 (IV); R =
H, R' = C6H5 (V); R = C6H4–OH-2, R' = H (VI).
707

708
GARIBOV et al.
Table 1. Yields and some physicochemical constants of I–VI
Found, %/Calculated, %
Yield,
Empirical
formula
Compound
%
Tm, °C
Rf
C
H
N
S
37 178–179 36.43 6.78 32.15 24.12 C4H9N3S
36.62 6.91 32.03 24.44
0.42
41
167
45.69 6.83 26.87 20.08 C6H11N3S
45.83 7.05 26.72 20.39
0.57
0.49
29 176–177 48.78 8.45 24.06 18.75 C7H15N3S
48.52 8.73 24.25 18.51
35 164–165 57.64 6.58 20.08 15.61 C10H13N3S 0.62
57.94 6.32 20.27 15.47
30 155–156 55.64 5.93 21.54 16.32 C9H11N3S
55.93 5.74 21.74 16.59
0.51
0.66
39 132–133 59.93 5.76 13.82 10.79
59.78 5.62 13.94 10.64
manifested at 1525, 1508, 1200, 1030, 919, and 625 cm–1
[12]. The stretching vibrations of the nonassociated
NH bond are revealed at 3445–3465 cm–1, and those of
associated NH bonds, at 3215–3225 cm–1.
Inthe1НNMRspectrumof2,6-bis(2-hydroxyphenyl)-
hexahydro-1,3,5-triazine-4-thione VI, the CH protons
give a singlet at 3.1 ppm. Aromatic ring protons give
doublets at 6.8, 7.2, and 7.4 ppm. The NH proton signal
is observed at 7.8 ppm. The two OH protons give
a singlet at 8.5 ppm.
Antioxidant properties of the synthesized cyclic
thioureas I–VI were studied in model reactions of
cumene autooxidation. Experiments showed that all
the compounds studied have pronounced antioxidant
properties and efficiently inhibit cumene oxidation.
To evaluate the capability of cyclic thioureas I–VI
to terminate oxidation chains in reactions with peroxy
radicals, we performed cumene oxidation in the presence
of I–VI, initiated with azobis(isobutyronitrile) (AIBN),
at 60°C. The initiator concentration was 2 × 10–2
M
in all the experiments. All the cyclic thioureas studied
inhibit the cumene oxidation. From the induction period
τ, we calculated the stoichiometric inhibition coefficient
f equal to the number of oxidation chains terminated on
one inhibitor molecule and its transformation products:
1
The Н NMR spectra of the other compounds are
similar to that of VI and differ only in the signals of
substituents. For example, the CH3N protons give
a singlet at 2.60 ppm, and nine protons of the tert-
butylamino group, a singlet at 1.25 ppm.
The 13С NMR spectra of the substances prepared
contain signals from carbon atoms of the benzene
ring (121, 126, 129, 131 ppm) and methine group
(39.40 ppm).
Wi
f =
,
[InH]0
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 83 No. 4 2010

CYCLIC THIOUREAS AS CUMENE OXIDATION INHIBITORS
709
where Wi is the initiation rate equal to 2 × 10–7 mol l–1
s–1 [13]; [InH]0, initial antioxidant concentration (M);
and τ, induction period (s).
properties. The kinetic parameters of the reactions of
I–VI with cumylperoxy radicals are given in Table 2.
As can be seen, the values of f for I–VI vary within
2.42–3.42. The rate constant of the reaction of the
antioxidants with cumylperoxy radicals varies from
2.10 × 104 to 4.75 × 104 l mol–1 s–1.
From the kinetics of the oxygen uptake, we calculated
the rate constant of the reaction of the antioxidants with
peroxy radicals K7. To this end, the kinetic curves of the
oxygen uptake were transformed from the coordinates
Δ[O2]–t into the coordinates Δ[O2]–1–t–1. From the
slope, equal to [14]
Analysis of the kinetic parameters of the reactions
of I–VI with cumylperoxy radicals shows that the
substituents at the triazine ring strongly affect the
reactivity of the compounds. For example, compound
VI, in contrast to the other antioxidants, repeatedly
terminates oxidation chains (f = 3.42) and exhibits
vary high reactivity toward cumylperoxy radicals (K7 =
4.75 × 104 l mol–1 s–1).
fK7[InH] 0
tan
=
,
K2[RH] Wi
we found
tan K2[RH] W
f [InH]0
The reactions of I–VI with cumene hydroperoxide
(CHP) were performed in chlorobenzene in a nitrogen
atmosphere at 110°C. All the compounds catalytically
decompose CHP. As seen from Fig. 2 showing data
for VI as example, the kinetic curve of the CHP
decomposition under the action of I–VI is S-shaped,
which is characteristic of an autocatalytic process
(Fig. 2).
i
K7 =
,
where K2 = 1.51 l mol–1 s–1 [15], [RH] = 6.9 M.
Figure 1 shows the kinetic curve of initiated oxidation
of cumene in the presence of cyclic thiourea VI taken
as example. As can be seen, compound VI inhibits
the oxidation by reacting with cumylperoxy radicals.
It is seen from the kinetic curve of initiated cumene
oxidation that the reaction rate in the presence of the
cyclic thiourea after the end of the induction period is
lower than the oxidation rate without inhibitor. This fact
indicates that the products formed from VI in reaction
with cumylperoxy radicals also exhibit antioxidant
ThecatalyticfactorνshowshowmanyCHPmolecules
decompose under the action of one antioxidant molecule.
This quantity is calculated by the formula
[ROOH]0 – [ROOH]
=
,
[InH]0
where [ROOH]0 and [ROOH]∞ are the initial and final
CHP concentrations, respectively; [InH]0 is the initial
antioxidant concentration.
Our results show that one molecule of I–VI is
capable to decompose up to several ten thousands of
c, M
τ = 142 min
τ, min
τ, min
Fig. 1. Kinetic curve of initiated oxidation of cumene in the
presence of VI. [AIBN] = 2 × 10–2 M, Т = 60°C, [InH] = 5 ×
10–4 M. (VO2) Oxygen uptake and (τ) time.
Fig. 2. Kinetic curve of CHP decomposition under the action
of VI. Т = 110°C, [InH] = 5 × 10–5 M. (с) CHP concentration
and (τ) time.
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710
GARIBOV et al.
Table 2. Kinetic parameters of reactions of I–VI with cumylperoxy radicals and of catalytic decomposition of cumene
hydroperoxide. [AIBN] = 2 × 10–2
M
Т 60°C
K7 × 10–4, l mol–1 s–1
Т 110°C
Compound
f
ν
K, × 10–4, l mol–1 s–1
τ, min
160
175
180
155
170
190
I
2.42
3.15
2.90
2.75
3.30
3.42
2.10
1.90
3.10
3.50
3.90
4.75
25000
27000
32000
45000
55000
65000
32
29
37
46
55
63
II
III
IV
V
VI
Cumene hydroperoxide was purified by the known
procedure [16] with the subsequent distillation;
chlorobenzene and cumene were purified by the common
procedure based on sulfonation of impurities with
concentrated sulfuric acid [17]. The CHP concentration
was determined by iodometric titration [18], with
intermittent sampling.
CHP molecules. Cyclic thiourea VI containing two
hydroxyphenyl fragments is the most active. For this
compound, the catalytic factor ν and the rate constant K
are equal to 65000 and 63 l mol–1 s–1, respectively.
Thus, the compounds under consideration exert
a combined effect as antioxidants: they terminate oxida-
tion chains in reactions with cumylperoxy radicals and
catalytically decompose cumene hydroperoxide.
Experiments on CHP decomposition were performed
in chlorobenzene at 110°C in a glass bubbler in a nitrogen
atmosphere. The CHP concentration was varied in the
range 0.16–0.64, and the concentration of I–VI, in the
range (1–5) × 10–4 M.
EXPERIMENTAL
1
The Н and 13С NMR spectra were recorded on
Experiments on initiated oxidation of cumene were
performed on a manometric unit [18]. The initiator
was AIBN, for which at 60°C the initiation rate is 1 ×
10–5 l mol–1 s–1. The initiator concentration in all the
experiments was constant (2 × 10–2 M), as well as the
concentration of I–VI, equal to 5 × 10–4 M.
a Bruker AVANCE 300 spectrometer (300 MHz) from
solutions in DMSO-d6, with HMDS as internal reference,
andtheIRspectra,onaSpecord75-IRspectrophotometer
from mulls in mineral oil. Thin-layer chromatography
of I–VI was performed on Silufol UV-254 plates, with
isopropyl alcohol : hexane (1 : 3) mixture as eluent.
2,6-Bis(2-hydroxyphenyl)hexahydro-1,3,5-
triazine-4-thione VI. A three-necked flask was charged
with 52 g (0.1 mol) of 33.5% aqueous ammonia and
7.6 g (0.1 mol) of thiourea dissolved in 30 ml of distilled
water. The mixture was vigorously stirred at 30–35°С.
Then 24.5 g (0.2 mol) of salicylaldehyde was added
dropwise, and the mixture was allowed to stand for 48 h
at room temperature. The precipitate was filtered off and
recrystallized from ethanol. Yield of VI 11.7 g (39%);
mp 132–133°C. Found, %: С 59.93, Н 5.76, N 13.82,
S 10.79. C15H15N3O2S. Calculated, %: C 59.78, H 5.62,
N 13.94, S 10.64; Rf 0.66.
CONCLUSIONS
(1) Ternary condensation of thiourea with aldehydes
and amines yields hexahydro-1,3,5-triazine-4-thiones.
(2) Cyclic thioureas exert a combined effect as
antioxidants: they terminate oxidation chains in reactions
with cumylperoxy radicals and catalytically decompose
cumene hydroperoxide.
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