3,5-Di-tert-butyl-4-hydroxybenzaldehyde derivatives as antioxidants in cumene oxidation

Article abstract of DOI:10.1134/S1070427212040180

A series of 4-hydroxy-3,5-di-tert-butylbenzaldehyde derivatives were prepared, and their antioxidant properties were studied.

Full text of DOI:10.1134/S1070427212040180

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2012, Vol. 85, No. 4, pp. 644−650. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.M. Magerramov, A.R. Askerova, E.Ya. Mamedov, I.A. Rzaeva, M.A. Allakhverdiev, 2012, published in Zhurnal Prikladnoi Khimii,
2012, Vol. 85, No. 4, pp. 628−634.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
3,5-Di-tert-butyl-4-hydroxybenzaldehyde Derivatives
as Antioxidants in Cumene Oxidation
A. M. Magerramov, A. R. Askerova, E. Ya. Mamedov,
I. A. Rzaeva, and M. A. Allakhverdiev
Baku State University, Baku, Azerbaijan
e-mail: rector@bsu.edu.az
Received August 17, 2010
Abstract—A series of 4-hydroxy-3,5-di-tert-butylbenzaldehyde derivatives were prepared, and their antioxidant
properties were studied.
DOI: 10.1134/S1070427212040180
Sterically hindered phenols are strong antioxidants
and efficiently inhibit oxidation of various organic
compounds. They readily react with peroxy radicals and
terminate oxidation chains [1]. Proceeding with stud-
ies in the field of synthesis and antioxidant behavior of
sulfur-containing additives [2–6], we prepared in this
work a series of 3,5-di-tert-butyl-4-hydroxybenzaldehyde
(1) derivatives.
Condensation of 3,5-di-tert-butyl-4-hydroxybenz-
aldehyde 1 with hydantoin gives hydantoin-substituted
2,6-di-tert-butylphenol 2:
OH
OH
O
C
NH
C
+
_H2O
O
H2C
OC
C
NH
C
S
CHO
CH
O
S
1
2
butyl-4-hydroxybenzaldehyde in methanol yields the
corresponding azomethine:
where ┼ = (CH3)3C.
The reaction of 4-arylthiazolamine with 3,5-di-tert-
OH
OH
C6H5
N
+
_H2O
C6H5
NH2
S
N
CHO
CH
N
S
3
Methylene-active carbonyl and dicarbonyl compounds
such as ethyl cyanoacetate, hydantoin, acetylacetone, and
dimedone enter into ternary condensation with 3,5-di-tert-
butyl-4-hydroxybenzaldehyde and 4-aryl-2-thiazolamine
Ternary condensation of 3,5-di-tert-butyl-4-hy-
droxybenzaldehyde, thiourea, and various amines yields
2,6-bis(3,5-di-tert-butyl-4-hydroxyphenyl)hexahydro-
1,3,5-triazine-4-thiones 4 and 5 (Scheme 1).
644

3,5-DI-tert-BUTYL-4-HYDROXYBENZALDEHYDE DERIVATIVES
645
Scheme 1.
OH
OH
CH
CH
NH
NR
C
+
H2NCNH2
+
R
NH2
S
_2H2O
NH
CHO
OH
4, 5
H (4), HOCH2CH2 (5).
Scheme 2.
OH
OH
C6H5
C6H5
N
+
+
R''H
N
NH2
S
NH CH
CH R''
S
CHO
6, 7
COCH3
OC
NH
C
6,
7
R'' =
CH
O
HC
COCH3
S
to form the corresponding derivatives. The ternary con-
densation usually follows Scheme 2.
In the IR spectrum of azomethine 3, the absorption
bands at 1620 and 1660 cm–1 correspond to C=N, and
that at 1040 cm–1, to C–N stretching vibrations.
All the synthesized compounds are yellow crystals or
oily masses soluble in many organic solvents. They were
usually recrystallized from alcohols. The physicochemi-
cal constants and analytical data are given in Table 1.
In the IR spectra of 2,6-bis(3,5-di-tert-butyl-4-
hydroxyphenyl)hexahydro-1,3,5-triazine-4-thiones 4
and 5, the C=S stretching vibrations are manifested at
1225–1190 cm–1. In contrast to the C=O band, the C=S
band in some cases is difficult to reveal. The NHCSNH
bands are manifested at 1335–1265 cm–1 [7]. In the IR
spectra of ternary condensation products 6 and 7 with
acetylacetone, the absorption band at 1575–1620 cm–1
corresponds to stretching vibrations of the enol carbonyl
group C=O. The other IR spectra are similar to those of 2.
The structures of the compounds synthesized were
1
proved by IR and Н and 13С NMR spectroscopy. The
purity was checked by elemental analysis and TLC.
The IR spectra of the compounds do not contain an
absorption band at 3615 cm–1, noted in [1]. In the IR
spectra of all the compounds, the phenolic hydroxyl band
was observed at 3190–3220 cm–1. The absorption bands
at 1690, 1750, and 1790 cm–1 are characteristic of the CO
bond in cyclic amides. In the IR spectrum of 2, the absorp-
tion bands at 1430 and 1450 cm–1 correspond to vibrations
of the C–N bonds, and those at 690–810 and 820 cm–1, to
out-of-plane wagging vibrations of the NH bond.
1
In the Н NMR spectrum of the initial 3,5-di-tert-
butyl-4-hydroxybenzaldehyde 1, 18 H atoms give a sin-
glet at 1.5–1.8 ppm. Two protons of the aromatic ring
give a singlet at approximately 8 ppm. We also revealed
the signal from the aldehyde proton (1 H) at 10.25 ppm.
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646
MAGERRAMOV et al.
Table 1. Physicochemical characteristics of products formed from compound 1
Found, %/Calculated, %
Compound Yield, %
Т, °С
Empirical formula
C18H13NO3S
Rf
C
H
N
S
2
3
4
5
6
7
86
83
35
46
22
44
150–151
64.62
64.84
6.76
6.95
4.47
4.20
9.48
9.62
0.61
103–104
147–148
127–128
132–133
195
72.63
72.32
8.35
8.60
7.28
7.03
8.01
8.04
C25H28N2OS
C31H47N3O2S
C33H47N3O3S
C27H32N3O3S2
C29H36N203S
0.45
0.45
0.87
0.81
0.82
70.98
70.81
8.85
9.01
7.72
7.99
6.28
6.10
74.81
74.29
10.54
10.31
5.66
5.30
4.43
4.05
65.27
65.46
7.59
7.65
8.42
8.18
12.43
12.48
72.44
72.54
8.51
8.93
5.83
5.64
5.38
6.45
In the 1Н NMR spectra of 2–7, in contrast to the start-
ing compound 1, we have not revealed the CHO signal.
At the same time, we revealed signals from hydantoin
(2), phenyl-2-thiazole, and dimedone.
azobis(isobutyronitrile) (AIBN), showed that the com-
pounds synthesized actively terminate oxidation chains
by reacting with cumylperoxy radicals (Fig. 2).
From the length of the induction period τind, we
calculated the stoichiometric coefficient of inhibition f,
equal to the number of oxidation chains terminated on
one molecule of inhibitor and its transformation products:
The compounds synthesized efficiently inhibit auto-
oxidation of cumene (Fig. 1).
Experiments on cumene oxidation in the presence
of 1–6 (60°С, [AIBN] = 2 × 10–2 M), initiated with
f = τindWin / [In]0,
where Win is the initiation rate, and [In]0 is the initial
inhibitor concentration.
From the kinetic curves of the oxygen uptake, we cal-
culated the rate constant of the reaction of the inhibitors
with peroxy radicals, k7 [1, 2]. To this end, the kinetic
curves were transformed from the coordinates V(O2)–τ
to the coordinates [O2]–1–τ–1, and k7 was found from the
slope of the straight line [2, 3],
tan α = f k7[In]0 / (k2[RH]Win),
where k2 is the chain initiation constant [2, 3], equal to
1.51 l mol–1 s–1, and [RH] = 7.17 M.
The kinetic parameters of the reactions of compounds
1–5 and 7 with cumylperoxy radicals {f, k7 (60°С,
[AIBN] = 2 × 10–2 M)} and of cumyl hydroperoxide de-
composition [k, ν (110°С)] are given in Table 2. As can be
seen, k7 varies within 1.6–4.09 l–1 mol–1 s–1 (with electron-
donor substituents, it is higher than with electron-acceptor
substituents). As for f, it varies in the range 1.2–2.16.
τ, min
Fig. 1. Kinetic curves of cumene autooxidation in the presence
of compounds 1–5 at 110°С. (V(O2)) Oxygen uptake and (τ)
reaction time; the same for Fig. 2. [In]0, M: (1') 0 and (1–5) 5 ×
10–5; numerals at curves are inhibitor nos.; the same for Fig. 2.
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3,5-DI-tert-BUTYL-4-HYDROXYBENZALDEHYDE DERIVATIVES
Table 2. Kinetic parameters of reactions of compounds 2–5 and 7
647
Т = 60°С
Т = 110°С
Т = 110°С
[In]0, M τ, min
Compd.
Formula
OH
f
k7 × 10–4, l mol–1 s–1 k, l mol–1 s–1
ν
20000 5 × 10–5
45000 5 × 10–5
30000 5 × 10–5
90
100
180
2
1.3
1.6
18.5
OC
C
NH
C
CH
OH
O
S
3
4
1.2
4.09
40
C6H5
N
CH
N
S
2.16
3.8
33
OH
CH
CH
NH
NH
NH
C
S
OH
40000 5 × 10–5
130
5
1.56
3.94
35
OH
CH
CH
NH
NH
NCH2CH2OH
C
S
OH
20000 5 × 10–5
150
7
1.8
1.72
28
C6H5
N
COCH3
COCH3
CH CH
NH
S
OH
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648
MAGERRAMOV et al.
τ, min
Fig. 3. Kinetic curve of CHP (ROOH) decomposition in the
presence of compounds 1. 110°С; [In]0 = 1 × 10–4, [ROOH]0 =
0.26 M. (τ) Time.
taken in excess. The catalytic factor ν characterizes the
number of CHP molecules decomposed by one inhibitor
molecule. It was calculated by the formula
ν = [ROOH]0–[ROOH]∞ /[In]0,
where [ROOH]0 and [ROOH]∞ are the initial and final
CHP concentrations, respectively, and [In]0 is the initial
inhibitor concentration.
Experiments showed that one molecule of 1–5 and
7 is capable to decompose tens of thousands of CHP
molecules (Table 2).
τ, min
Fig. 2. Kinetic curves of initiated cumene oxidation in the pres-
ence of compounds 1–5.
EXPERIMENTAL
The Н and 13С NMR spectra were recorded with
1
The reactions of 1–6 with cumyl hydroperoxide
(CHP) were performed in chlorobenzene under nitrogen
at 110°С. All the compounds tested decompose CHP. As
demonstrated by the example of inhibitor 1 (Fig. 3), the
kinetic curve of CHP decomposition under the action of
the compounds tested is S-shaped, which is characteristic
of an autocatalytic process. Initially there is certain induc-
tion period when the CHP consumption is insignificant,
then it is followed by rapid catalytic decomposition, after
which the reaction rate decreases because of a decrease
in the CHP concentration.
a Bruker-300 spectrometer (300 MHz) of the Avance
system. The IR spectra were taken with a Specord 75-
IR spectrometer from mulls in mineral oil. Thin-layer
chromatography of 1–5 and 7 was performed with Silufol
UV-254 plates, using 1 : 1 isopropanol–hexane mixture
as eluent.
Isopropylbenzene (cumene) (MW 120.2, Тb 152°С,
d29.3 862 kg m–3, nD29.3 1.49146) was washed, dried, and
distilled under reduced pressure. The cumene purity was
checked kinetically, by AIBN-initiated oxidation at 333
K, using a manometric installation [8].
Probably, the inhibitor first reacts with CHP, and then
the transformation product formed catalytically decom-
poses CHP.
Cumyl hydroperoxide (MW 152, Тb 53°С/13.3 Pa,
d29.3 1062 kg m–3, nD29.3 1.5240). Technical-grade cumyl
hydroperoxide was shaken with freshly calcined alumina
with two- or threefold adsorbent replacement. The pre-
To determine the reaction stoichiometry, CHP was
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3,5-DI-tert-BUTYL-4-HYDROXYBENZALDEHYDE DERIVATIVES
649
tals were obtained; yield 3.4 g (46%), Тm 130–131°С,
Rf 0.71, eluent isopropanol. Found, %: C 69.81, H 8.54,
N 7.66, S 5.43. C33H47N3O3S. Calculated, %: C 70.05,
H 8.37, N 7.43, O 8.48, S 5.67.
cipitate was filtered off, after which CHP was vacuum-
distilled twice at 13.3 Pa. Its purity was monitored by the
refractive index, density, and available oxygen content
determined by iodometric titration [9].
3,5-Di-tert-butyl-4-hydroxybenzaldehyde (1). To a
solution of 17.5 g of boric acid and 12.5 g of hexamethy-
lenetetramine in 75 ml of ethylene glycol, heated to 130°С,
we added dropwise 9 g of 2,6-di-tert-butylphenol. The
reaction mixture was stirred for 180 min at 130–135°С,
after which 75 ml of dilute (30%) sulfuric acid was slowly
added. The oil precipitated in the process crystallizes on
cooling. The crystals were washed with cold ethanol and
filtered off. White crystals, yield 70%, Rf = 0.93, eluent
isopropanol–hexane (1 : 1), Тm 185–186°С (published
data [10]: Тm 185–186°С).
5-[4-Phenylthiazol-2-ylamino(3,5-di-tert-butyl-
4-hydroxyphenyl)methyl]thiazolidine-2,4-dione (6).
A three-necked flask equipped with a stirrer, a reflux
condenser, and a thermometer was charged with 2.34 g
(0.01 mol) of 3,5-di-tert-butyl-4-hydroxybenzaldehyde
(1), 1.76 g (0.01 mol) of phenylthiazolamine, 1.17 g
(0.01 mol) of thiazolidine-2,4-dione, and 20 ml of n-buta-
nol. The mixture was stirred for 2 days at 115–120°С. The
orange crystals obtained were washed with hexane; yield
21%, Тm 132–133°С, Rf 0.81, eluent isopropanol. Found,
%: C 63.27, H 6.59, N 8.42, S 12.43. C27H32N3O3S.
Calculated, %: C 63.50, H 6.32, N 8.23, O 9.40, S 12.56.
2,6-Di-tert-butyl-4-[(4-phenylthiazol-2-ylimino)
methyl]phenol (3).Athree-necked flask equipped with a
water-separating column, a reflux condenser, a thermom-
eter, and a glass stirrer was charged with 7.2 g (0.03 mol)
of 3,5-di-tert-butyl-4-hydroxybenzaldehyde (1), 5.28 g
(0.03 mol) of 2-amino-4-phenylthiazole, and 20 ml of
methanol. The mixture was stirred for 4 h at 60–65°С.
To remove the released water completely, a small amount
of benzene was added to the reaction mixture. Yellow
crystals were obtained; yield 10.2 g (83%), Rf 0.45, elu-
ent isobutanol–decane (1 : 5), Тm 103–104°С. Found, %:
C 73.63, H 7.35, N 7.28, S 8.04. C24H28N2OS. Calculated,
%: C 73.43, H 7.19, N 7.14, S 8.17.
3-[4-Phenylthiazol-2-ylamino(3,5-di-tert-butyl-
4-hydroxyphenyl)methyl]pentane-2,4-dione (7).
A three-necked flask equipped with a stirrer, a reflux
condenser, and a thermometer was charged with 2.34 g
(0.01 mol) of 3,5-di-tert-butyl-4-hydroxybenzaldehyde (1),
1.76 g (0.01 mol) of 2-amino-4-phenylthiazole, 10.8 ml
(0.01 mol) of acetylacetone, and 20 ml of n-butanol. The
mixture was stirred for 6 h at 115–116°С. The yellow
crystals obtained were washed with dichloromethane; yield
44%, Тm 195°С, Rf 0.82, eluent isopropanol–decane (1 : 5).
Found, %: C 70.44, H 7.51, N 5.83, S 6.38. C29H36N2O3S.
Calculated, %: C 70.70, H 7.37, N 5.69, O 9.74, S 6.51.
4,6-Bis(3,5-di-tert-butyl-4-hydroxyphenyl)he-
xahydro-1,3,5-triazine-2-thione (4). A three-necked
flask was charged with 2.34 g (0.01 mol) of 3,5-di-tert-
butyl-4-hydroxybenzaldehyde (1), 0.76 g (0.01 mol)
of thiourea, and 1.24 ml (0.01 mol) of methylamine.
The mixture was left in a fume hood for 7 days at room
temperature with continuous stirring. The reaction
mixture color gradually changed from white to yellow.
Yellow crystals were obtained; yield 1.25 g (35%),
Тm 147–148°С, Rf 0.45, eluent isobutanol–decane (3 : 5).
Found, %: C 70.98, H 8.85, N 7.72, S 6.28. C31H47N3O2S.
Calculated, %: C 70.81, H 9.01, N 7.99, O 6.09, S 6.10.
CONCLUSIONS
(1) A series of 3,5-di-tert-butyl-4-hydroxybenzal-
dehyde derivatives were prepared. With hydantoin, С
hydantoin-substituted 2,6-di-tert-butylphenol was ob-
tained in 86% yield.
(2) Ternary condensation of 3,5-di-tert-butyl-4-
hydroxybenzaldehyde, thiourea, and various amines was
performed, and the corresponding 2,6-bis(3,5-di-tert-bu-
tyl-4-hydroxyphenyl)hexahydro-1,3,5-triazine-4-thiones
were obtained.
4,6-Bis(3,5-di-tert-butyl-4-hydroxyphenyl)-5-(2-
hydroxyethyl)hexahydro-1,3,5-triazine-2-thione (5).
A three-necked flask equipped with a stirrer, a reflux
condenser, and a thermometer was charged with the fol-
lowing reactants (0.025 mol each): 5.8 g of 3,5-di-tert-
butyl-4-hydroxybenzaldehyde (1), 1.9 g of thiourea, and
1.4 ml of ethanolamine, and also with 20 ml of benzene.
The mixture was stirred for 2 days at 72°С. Yellow crys-
(3) 3,5-Di-tert-butyl-4-hydroxybenzaldehyde deriva-
tives react with cumylperoxy radicals and thus actively
terminate oxidation chains.
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