Synthesis and antioxidative activity of N, N-dialkyl-ω-[4- hydroxy(methoxy)aryl]alkylamines and their N-oxides

Article abstract of DOI:10.1007/s11167-005-0391-z

Aminoalkylphenols of various structures were prepared by reactions of ω-[4-hydroxy(methoxy)aryl]haloalkanes with dialkylamines. The corresponding N-oxides were prepared by oxidation of aminoalkylphenols with hydrogen peroxide and cumene hydroperoxide. The

Full text of DOI:10.1007/s11167-005-0391-z

Russian Journal of Applied Chemistry, Vol. 78, No. 5, 2005, pp. 781 786. Translated from Zhurnal Prikladnoi Khimii, Vol. 78, No. 5,
2005, pp. 796 801.
Original Russian Text Copyright
2005 by Dyubchenko, Nikulina, Terakh, Prosenko, Grigor’ev.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis and Antioxidative Activity
of N, N-Dialkyl- -[4-hydroxy(methoxy)aryl]alkylamines
and Their N-Oxides
O. I. Dyubchenko, V. V. Nikulina, E. I. Terakh, A. E. Prosenko, and I. A. Grigor’ev
Research Institute of Chemistry of Antioxidants, Novosibirsk State Pedagogical University, Novosibirsk, Russia
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
Novosibirsk, Russia
Received September 1, 2004; in final form, January 2005
Abstract Aminoalkylphenols of various structures were prepared by reactions of -[4-hydroxy(methoxy)-
aryl]haloalkanes with dialkylamines. The corresponding N-oxides were prepared by oxidation of aminoalkyl-
phenols with hydrogen peroxide and cumene hydroperoxide. The inhibiting activities of these compounds in
a model reaction of thermal autooxidation of lard were compared.
Aminoalkylphenols containing a phenolic fragment
and an alkylamino group are highly effective inhibit-
ors of free-radical oxidation of various organic sub-
strates. According to patent data [1 3], they can be
used as stabilizers of polymeric materials, rubbers,
lubricating oils, and diesel and jet fuels. Furthermore,
aminoalkylphenols show a wide spectrum of biologi-
cal activity; in particular, they exhibit antiphlogistic,
antirheumatic, antiallergic, antidiabetic, and other
properties [4 10]. The mechanism of the antioxidative
effect of aminoalkylphenols responsible for their high
performance is not yet fully elucidated; for its better
understanding, it is necessary to study the structure
inhibiting activity relationship for aminoalkylphenols
and to examine their oxidation products in which one
of the groups responsible for the antioxidative power
is inactivated.
R3
R1 O
(CH2)nHlg
R2
I VI
R3
2
(R )
NH
2
R1 O
,
(CH ) N (R4 )
2
n
K CO
2
3
2
R2
VII XVI
1
2
3
where R = H, R = R = t-Bu: n = 2, Hlg = Cl (I);
4
n = 2, R = Me (VII), Et (VIII); n = 3, Hlg = Cl (II);
n = 3, R = Me (IX), Et (X), Pr (XI); n = 4, Hlg = Cl
(III); n = 4, R = Me (XII), Et (XIII); R = R = H,
R = t-Bu, n = 3: Hlg = Cl (IV), R = Me (XIV);
R = R = R = H, n = 3: Hlg = Br (V), R = Me
(XV); R = Me, R = R = H, n = 3: Hlg = Br (VI),
4
4
1
2
3
4
1
2
3
4
1
2
3
Therefore, in this study we prepared aminoalkyl-
phenols differing in the extent of steric shielding of
the phenolic OH group, structure of the N-substitu-
ents, and distance between the amino group and aro-
matic core; also we prepared the corresponding N-ox-
ides and compared the inhibiting powers of the com-
pounds synthesized in the model reaction of thermal
autooxidation of lard.
4
R
= Me (XVI).
The syntheses were performed in ampules in ethan-
ol in the presence of K CO at 120 C for 7 h; the
molar ratio of the starting haloalkane, dialkylamine,
and K CO was 1: 2 : 2. Yields of VII XVI 60 93%.
2
3
2
3
It is known [11 14] that tertiary aliphatic amines
react with peroxy compounds to form N-oxides. We
performed the oxidation of aminoalkylphenols IX XI
with hydrogen peroxide and cumene hydroperoxide
in 2-propanol at 60 C for 3 h and obtained the corre-
By the reaction of -[4-hydroxy(methoxy)aryl]-
haloalkanes I VI with dialkylamines, we prepared the
corresponding alkylphenols VII XVI:
1070-4272/05/7805-0781 2005 Pleiades Publishing, Inc.

782
DYUBCHENKO et al.
Induction period of lard oxidation, inhibited by phenolic
antioxidants (1.5 mol g , 130 C)
that compounds VIII, XI XIV, and XVII XIX were
unknown previously. Aminoalkylphenol VII is men-
tioned in [6] without spectral characteristics, and
amines XV and XVI are reported in [8] only as hydro-
chlorides.
1
Antioxidant*
, min
R(CH2)2N(Me)2 (VII)
R(CH2)2N(Et)2 (VIII)
R(CH2)3N(Me)2 (IX)
R(CH2)3N(Et)2 (X)
R(CH2)3N(Pr)2 (XI)
R(CH2)4N(Me)2 (XII)
R(CH2)4N(Et)2 (XIII)
R (CH2)3N(Me)2 (XIV)
R"(CH2)3N(Me)2 (XV)
R(CH2)3N(O)(Me)2 (XVII)
R(CH2)3N(O)(Et)2 (XVIII)
R(CH2)3N(O)(Pr)2 (XIX)
RCH2N(Me)2 (XX)
288 10
298 7
334 5
307 5
277 7
435 5
335 5
143 5
51 5
170 5
150 5
110 5
110 5
165 5
20 3
The antioxidative activity (AOA) of aminoalkyl-
phenols VII XV and their N-oxides XVII XIX was
evaluated from their inhibiting effect on thermal auto-
oxidation of lard. As references we used commercial
inhibitors 2,6-di-tert-butyl-4-methylphenol (Ionol) and
N, N-dimethyl(3,5-di-tert-butyl-4-hydroxybenzyl)-
amine XX, and also a 1 : 1 synergistic mixture of
Ionol and N, N-dimethyldodecylamine (DMDA).
We found that di-tert-butyl-substituted aminoalkyl-
phenols VII XIII are effective inhibitors of lard oxi-
dation (see table); in their antioxidative power they
appreciably surpass the commercial antioxidants and
the Ionol DMDA mixture.
RCH3 (Ionol)
C12H25N(Me)2 (DMDA)
RCH3 + DMDA (synergistic mixture)
Control
198 5
20 3
A previous study of the antiradical activity of 2,6-
di-tert-butyl-substituted aminoalkylphenols VII, IX,
and XX in a model reaction of initiated oxidation of
methyl oleate in chlorobenzene at 60 C showed that
these compounds are highly reactive toward peroxy
* R = 3,5-di-tert-butyl-4-hydroxyphenyl, R = 3-tert-butyl-4-
hydroxyphenyl, and R" = 4-hydroxyphenyl.
radicals [15]. The rate constants k of their reaction
with peroxy radicals
7
sponding N-oxides XVII XIX in 43 90% yields:
.
.
PhOH + ROO
PhO + ROOH
(1)
(CH ) (R)
3N
HO
2
2
were similar to those characteristic of Ionol. This fact
suggests that the higher inhibiting power of amino-
alkylphenols VII XIII, compared to Ionol, in auto-
oxidation of lard is due to the bifunctional mechanism
of theit antioxidative effect, namely, to a combination
of the antiradical activity of the phenolic group and
antioxidative activity of the alkylamino group. The
significance of the contribution of the alkylamino
group to AOA of aminoalkylphenols is also confirmed
by the fact that the corresponding N-oxides XVII
XIX are comparable with, or even inferior to Ionol as
inhibitors of lard oxidation. The low AOA of benzyl-
amino derivative XX compared to aminoalkylphenols
VII XIII in oxidation of lard at 130 C is apparently
caused by the thermal instability of XX [16].
IX XI
XOOH
(CH )
3N(O)(R)2,
HO
2
XVII XIX
where X = H, PhC(Me) ; R = Me (XVII), Et (XVIII),
2
Pr (XIX).
The compositions and structures of aminoalkyl-
phenols VII XVI and their N-oxides XVII XIX were
confirmed by elemental analysis and spectroscopy.
1
In the H NMR spectra of N-oxides XVII XIX, com-
pared to the corresponding aminoalkylphenols IX XI,
the signals of the methylene protons of the p-alkyl
substituent are shifted downfield, which suggests an
increase in the polarizing power of the N-containing
fragment, i.e., its oxidation. The IR spectra of XVII
It is known [17, 18] that aliphatic amines in mix-
tures with phenolic antioxidants can act as synergistic
agents. The synergistic effect is usually evaluated by
the induction period and characterized by
2),
is the induction period in the presence of
[19]:
syn
1
XIX contain absorption bands at 950 970 cm ,
=
(
+
1
syn
1,2
characteristic of the N O stretching vibrations. These
bands are absent in the spectra of the corresponding
aminoalkylphenols IX XI.
where
1, 2
two inhibitors;
presence of individual inhibitors.
and , induction periods in the
1
2
A search in the STN International database showed
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 78 No. 5 2005

SYNTHESIS AND ANTIOXIDATIVE ACTIVITY OF N, N-DIALKYL-...
783
In the experiments on lard oxidation, the nonaddi-
tive effect of coinhibitors was revealed for the system
Ionol DMDA; the synergistic effect, calculated by the
formula
ents and extent of steric shielding of the phenolic OH
group. In going from N, N-dimethyl-substituted amine
IX to its diethyl (X) and dipropyl (XI) analogs, the
inhibiting activity decreased.
Aminoalkylphenols differing in the extent of steric
shielding of the phenolic OH group can be ranked in
the following order with respect to the capability to
inhibit lard oxidation: IX > XIV > XV. A decrease in
AOA of aminoalkylphenols in this series corresponds
to an increase in the reactivity of the corresponding
phenoxy radicals in the reaction
= (
)
(
+
2 ),
0
syn
PhOH + DMDA
0
DMDA
PhOH
where
is the induction period of the noninhibited
and , induction peri-
0
oxidation of lard;
DMDA
PhOH
ods in the presence of DMDA and Ionol, respectively;
and , induction period in the presence of
PhOH+DMDA
the Ionol DMDA mixture, amounted to 33 min. For
2,6-di-tert-butyl-substituted aminoalkylphenols VII
XIII, the synergistic effect was more pronounced, and
.
.
PhO + RH
PhOH + R .
(2)
, calculated as
syn
In particular, according to the existing estimates,
3
4
= (
)
(
+
2 ),
0
syn
AAP
0
DMDA
PhOH
o-unsubstituted phenoxyls are 10 10 times (at 60 C)
more active than 2,6-di-tert-butyl-substituted phenoxy
radicals [23]. Compound XV at the o-positions con-
tains no bulky tert-butyl substituents sterically hinder-
ing reaction (2), which accounts for the lowest AOA
of this compound in the examined series.
where
is the induction period of lard oxidation
AAP
in the presence of aminoalkylphenols, ranged from
112 to 270 min. Thus, we can state that the high anti-
oxidative acitivity of aminoalkylphenols in lard oxida-
tion is associated not only with the bifunctional mech-
anism of their antioxidative effect but also with the
pronounced synergistic effect which, most likely, is of
intramolecular origin and is due to structural features
of these molecules.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
spectrometer (500 MHz), solvents CDCl and CD OD,
internal reference TMS; the IR spectra were taken on
The occurrence of intramolecular synergism in
bifunctional inhibitors, in particular, in sulfur-contain-
ing derivatives of sterically hindered phenols, was
repeatedly discussed in [20 22]; however, its origin
was not elucidated. The intramolecular synergism may
be due to favorable steric arrangement of the phenolic
and sulfur-containing fragments, allowing the hydro-
peroxide formed by reaction (1) to be deactivated with
the sulfur-containing fragment without escaping into
the bulk of the substrate [22]. A similar pattern can be
expected for aminoalkylphenols.
3
3
a Specord M80 spectrometer in CHCl . The melting
3
points were determined on a PTP device. The starting
-[4-hydroxy(methoxy)aryl]haloalkanes I VI were
prepared as described previously [24], and N, N-di-
methyl(3,5-di-tert-butyl-4-hydroxybenzyl)amine XX,
by the procedure described in [3].
N, N-Dimethyl-2-(3,5-di-tert-butyl-4-hydroxy-
phenyl)ethylamine VII. A 50-ml ampule was charged
with 5.0 g (18.6 mmol) of chloride I, 5.1 g of dimeth-
ylamine solution (37.2 mmol), 5.1 g (37.2 mmol) of
K CO , and 10 ml of ethanol. The ampule was sealed,
Since the extent of the intramolecular synergism
can depend on the distance between the alkylamino
group and aromatic core, the difference in the AOA
of aminoalkylphenols VII X, XII, XIII, and XX
containing different number of carbon atoms in the
p-alkyl chain becomes quite understandable. In the
series of N, N-dimethyl- and diethyl-substituted ami-
noalkylphenols, in the most effective inhibitors of lard
oxidation the alkylamino group was separated from
the aromatic core by four carbon atoms. Apparently,
in this case the mutual arrangement of the phenolic
and alkylamino groups is the most favorable for the
intramolecular synergism.
2
3
placed in a thermostat equipped with a shaker, and
heated for 7 h at 120 C. After cooling, the ampule
was opened, and the reaction mixture was treated with
alkali and extracted with toluene. The extract was
washed with water and dried over Na SO ; the solvent
2
4
was distilled off, and the residue was distilled in a
vacuum. Yield of amine VII 4.0 g (78%), bp 140
1
142 C (1 mm Hg), mp 84 85 C. H NMR spectrum,
, ppm: 1.44 s (18H, t-Bu), 2.32 s [6H, N(CH ) ],
3 2
2.55 m (2H, CH N), 2.69 m (2H, ArCH ), 4.91 s (1H,
2
2
1
OH), 6.99 s (2H, H
). IR spectrum, , cm : 3640
The antioxidative activity of aminoalkylphenols
arom
also strongly depended on the structure of N-substitu-
(OH).
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 78 No. 5 2005

784
Found, %: C 78.08, H 11.47, N 5.39.
DYUBCHENKO et al.
CH CH ) ], 1.77 m (2H, ArCH CH ), 2.43 t [4H,
2
3 2
2
2
C18H31ON.
N(CH CH CH ) ], 2.48 t (2H, CH N), 2.58 t (2H,
2
2
2
3 2
2
Calculated, %: C 77.92, H 11.26, N 5.05.
ArCH ), 4.96 s (1H, OH), 6.97 s (2H, H
). IR
arom
1
spectrum, , cm : 3640 (OH).
N, N-Diethyl-2-(3,5-di-tert-butyl-4-hydroxyphen-
yl)ethylamine VIII was prepared similarly from 5.2 g
(19.3 mmol) of chloride I, 2.8 g (38.7 mmol) of di-
ethylamine, and 5.4 g (38.7 mmol) of K CO . Yield
Found, %: C 79.89, H 11.95, N 4.05.
C23H41ON.
Calculated, %: C 79.49, H 11.89, N 4.03.
2
3
1
5.4 g (91%), bp 122 124 C (1 mm Hg). H NMR
spectrum, , ppm: 1.08 t [6H, N(CH CH ) ], 1.45 s
N, N-Dimethyl-4-(3,5-di-tert-butyl-4-hydroxy-
phenyl)butylamine XII was prepared similarly from
5.0 g (16.8 mmol) of III, 4.6 g of dimethylamine
solution (33.7 mmol), and 4.7 g (33.7 mmol) of
K CO . Yield 4.4 g (85%), bp 148 150 C (1 mm
2
3 2
(18H, t-Bu), 2.63 q [4H, N(CH CH ) ], 2.69 s (4H,
2
3 2
ArCH CH ), 5.07 s (1H, OH), 7.01 s (2H, H ).
2
2
arom
1
IR spectrum, , cm : 3640 (OH).
2
3
Found, %: C 78.48, H 11.47, N 4.24.
C20H35ON.
Calculated, %: C 78.63, H 11.55, N 4.58.
1
Hg), mp 90 91 C. H NMR spectrum, , ppm: 1.47 s
(18H, t-Bu), 1.57 m (2H, ArCH CH CH ), 1.63 m
2
2
2
(2H, ArCH CH ), 2.26 s [6H, N(CH ) ], 2.32 t (2H,
2
2
3 2
CH N), 2.58 t (2H, ArCH ), 5.07 s (1H, OH), 7.01 s
N, N-Dimethyl-3-(3,5-di-tert-butyl-4-hydroxy-
phenyl)propylamine IX was prepared similarly from
5.0 g (17.7 mmol) of chloride II, 4.8 g of dimethyl-
amine solution (35.4 mmol), and 4.9 g (35.4 mmol) of
K CO . Yield 4.6 g (90%), bp 130 C (1 mm Hg), mp
2
2
1
(2H, H
). IR spectrum, , cm : 3640 (OH).
arom
Found, %: C 78.97, H 11.81, N 4.65.
C20H35ON.
Calculated, %: C 78.63, H 11.55, N 4.58.
2
3
1
44 45 C (published data: 31 33 C) [5]. H NMR
spectrum, , ppm: 1.49 s (18H, t-Bu), 1.82 m (2H,
ArCH CH ), 2.30 s [6H, N(CH ) ], 2.38 t (2H,
N, N-Diethyl-4-(3,5-di-tert-butyl-4-hydroxyphen-
yl)butylamine XIII was prepared similarly from
5.2 g (17.5 mmol) of III, 2.6 g (35.0 mmol) of dieth-
ylamine, and 4.8 g (35.0 mmol) of K CO . Yield
2
2
3 2
CH N), 2.60 t (2H, ArCH ), 5.11 s (1H, OH), 7.06 s
(2H, H
2
2
1
). IR spectrum, , cm : 3640 (OH).
arom
2
3
1
5.3 g (91%), bp 145 147 C (1 mm Hg). H NMR
Found, %: C 78.11, H 11.58, N 4.81.
C19H33ON.
Calculated, %: C 78.29, H 11.41, N 4.85.
spectrum, , ppm: 1.06 t [6H, N(CH CH ) ], 1.48 s
2
3 2
(18H, t-Bu), 1.60 m (4H, ArCH CH CH ), 2.49
2
2
2
2.58 m [8H, N(CH CH ) , CH N, ArCH ], 5.05 s
2
3 2
arom
2
2
1
N, N-Diethyl-3-(3,5-di-tert-butyl-4-hydroxyphen-
yl)propylamine X was prepared similarly from 4.7 g
(16.7 mmol) of chloride II, 2.4 g (33.4 mmol) of di-
ethylamine, and 4.6 g (33.4 mmol) of K CO . Yield
(1H, OH), 7.02 s (2H, H
3640 (OH).
). IR spectrum, , cm :
Found, %: C 79.65, H 11.81, N 4.05.
C22H39ON.
2
3
1
4.9 g (93%), bp 150 153 C (1 mm Hg). H NMR
Calculated, %: C 79.92, H 11.78, N 4.20.
spectrum, , ppm: 1.04 t [6H, N(CH CH ) ], 1.46 s
2
3 2
(18H, t-Bu), 1.79 m (2H, ArCH CH ), 2.50 2.58 m
2
2
N, N-Dimethyl-3-(3-tert-butyl-4-hydroxyphenyl)-
propylamine XIV was prepared similarly from 5.0 g
(22.1 mmol) of chloride IV, 6.0 g of dimethylamine
solution (44.1 mmol), and 6.1 g (44.1 mmol) of
[8H, ArCH , CH N, N(CH CH ) ], 5.05 s (1H, OH),
2
2
2
3 2
1
7.02 s (2H, H
). IR spectrum, , cm : 3640 (OH).
arom
Found, %: C 78.82, H 11.75, N 4.22.
C21H37ON.
Calculated, %: C 78.94, H 11.67, N 4.38.
1
K CO . Yield 4.4 g (85%), mp 90 91 C. H NMR
2
3
spectrum, , ppm: 1.39 s (9H, t-Bu), 1.80 m (2H,
ArCH CH ), 2.27 s [6H, N(CH ) ], 2.36 t (2H,
2
2
3 2
N, N-Dipropyl-3-(3,5-di-tert-butyl-4-hydroxy-
phenyl)propylamine XI was prepared similarly from
5.0 g (17.5 mmol) of chloride II, 3.8 g (35.1 mmol)
of dipropylamine, and 4.8 g (35.1 mmol) of K CO .
CH N), 2.51 t (2H, ArCH ), 6.48 d (1H, H
),
2
2
arom
6.78 d.d (1H, H
(1H, OH). IR spectrum, , cm : 3608 (OH).
), 7.01 d (1H, H
), 8.0 br.s
arom
arom
1
2
3
1
Yield 5.1 g (84%), bp 161 164 C (2 mm Hg). H
NMR spectrum, , ppm: 0.96 t [6H, N(CH CH
Found, %: C 76.28, H 10.25, N 5.30.
C15H25ON.
Calculated, %: C 76.55, H 10.70, N 5.52.
2
2
2
CH ) ], 1.51 s (18H, t-Bu), 1.51 m [4H, N(CH
3 2
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 78 No. 5 2005

SYNTHESIS AND ANTIOXIDATIVE ACTIVITY OF N, N-DIALKYL-...
785
N, N-Dimethyl-3-(4-hydroxyphenyl)propylamine
XV was prepared similarly from 5.0 g (23.3 mmol)
of bromide V, 6.4 g of dimethylamine solution
(46.5 mmol), and 6.4 g (46.5 mmol) of K CO . The
mene hydroperoxide. The procedure was similar to
that described above. Yield 0.9 g (43%).
N, N-Diethyl-3-(3,5-di-tert-butyl-4-hydroxyphen-
yl)propylamine N-oxide XVIII was prepared similar-
ly by oxidation of 2.0 g (6.3 mmol) of X with 0.76 ml
2
3
contents of the ampule were transferred into a round-
bottomed flask, and the solvent was distilled off on
a rotary evaporator. The dry residue was dissolved in
ethanol on heating, and the undissolved substance was
filtered off. The solvent from the filtrate was distilled
off, and the target product was recrystallized from
of hydrogen peroxide solution (9.4 mmol). Yield 1.7 g
1
(82%), mp 167 C. H NMR spectrum (CDCl ),
,
3
ppm: 1.21 s [6H, N(CH CH ) ], 1.37 s (18H, t-Bu),
1.98 m (2H, ArCH CH ), 2.50 t (2H, ArCH ), 3.00 t
(2H, CH N), 3.10 q [4H, N(CH CH ) ], 5.17 s (1H,
2
3 2
2
2
2
1
2
2
3 2
benzene. Yield 2.5 g (61%), mp 114 116 C. H NMR
1
OH), 6.84 s (2H, H
). IR spectrum, , cm : 3640
arom
spectrum, , ppm: 1.77 m (2H, ArCH CH ), 2.24 s
2
2
(OH), 948 (NO).
[6H, N(CH ) ], 2.32 t (2H, CH N), 2.54 t (2H,
3 2
2
ArCH ), 5.05 s (1H, OH), 6.73 d (2H, H
), 7.03 d
Found, %: C 75.48, H 11.70, N 4.30.
C21H37NO2.
Calculated, %: C 75.17, H 11.11, N 4.18.
2
arom
1
(2H, H
). IR spectrum, , cm : 3612 (OH).
arom
Found, %: C 73.58, H 9.44, N 7.93.
C11H17ON.
Calculated, %: C 73.70, H 9.56, N 7.81.
N, N-Dipropyl-3-(3,5-di-tert-butyl-4-hydroxy-
phenyl)propylamine N-oxide XIX was prepared
similarly by oxidation of 1.0 g (2.9 mmol) of amine
XI with 0.35 ml of hydrogen peroxide solution
N, N-Dimethyl-3-(4-methoxyphenyl)propylamine
XVI was prepared similarly from 5.7 g (24.4 mmol)
of bromide VI, 6.7 g of dimethylamine solution
(48.8 mmol), and 6.7 g (48.8 mmol) of K CO . Yield
1
(4.3 mmol). Yield 0.8 g (80%), mp 105 C. H NMR
spectrum (CDCl ), , ppm: 0.92 t [6H, N(CH CH
3
2
2
2
CH ) ], 1.40 s (18H, t-Bu), 1.70 m [4H, N(CH CH
2
3
3 2
3 2
2
1
4.0 g (85%), bp 108 110 C (1 mm Hg). H NMR
CH ) ], 2.02 m (2H, ArCH CH ), 2.52 t (2H, Ar
2
2
spectrum, , ppm: 1.78 m (2H, ArCH CH ), 2.22 s
CH ), 3.10 t [4H, N(CH CH CH ) ], 3.15 m (2H, Ar
2
2
2
2
2
3 2
[6H, N(CH ) ], 2.32 t (2H, CH N), 2.57 t (2H,
CH CH CH ), 5.00 s (1H, OH), 6.87 s (2H, H
).
3 2
2
2
2
2
arom
1
IR spectrum, CHCl , , cm : 3640 (OH), 966 (NO).
ArCH ), 3.70 s (3H, OCH ), 6.85 d (2H, H
),
3
2
3
arom
7.12 d (2H, H
).
arom
Found, %: C 76.03, H 11.54, N 3.93.
C23H41NO2.
Calculated, %: C 75.98, H 11.37, N 3.85.
Found, %: C 74.28, H 10.03, N 7.55.
C12H19ON.
Calculated, %: C 74.57, H 9.91, N 7.24.
We also examined the inhibiting activity of 2,6-di-
tert-butyl-4-methylphenol (Ionol) and N, N-dimethyl-
dodecylamine (Acros Organics). Oxidation of lard
(Novosibirsk Meat-Canning Plant) was performed
under the conditions of oxygen bubbling at 130 C in
an oxidation cell similar to that described in [19]. The
weight of the lard sample was 50 g, and AO concen-
tration, 1.5 mol per gram of lard. In the course of the
oxidation, 1-g samples of the lard were taken, and the
concentration of peroxy compounds was determined
by iodometric titration [25]. The kinetic curves were
plotted (see figure), and the induction period (time in
which the lard was oxidized to a peroxide number of
0.1) was determined graphically. All the measure-
ments were repeated 3 4 times; the mean results with
the rms errors are listed in the table.
N, N-Dimethyl-3-(3,5-di-tert-butyl-4-hydroxy-
phenyl)propylamine N-oxide XVII. To a solution of
2.0 g (6.9 mmol) of amine IX in 15 ml of 2-propanol,
we added 0.84 ml (10.3 mmol) of 30% H O . The
2
2
mixture was stirred at 60 C for 3 h, the solvent was
distilled off, and the residue was recrystallized from
1
toluene. Yield 1.9 g (90%), mp 165 C. H NMR spec-
trum, , ppm: 1.43 s (18H, t-Bu), 2.21 m (2H, Ar
CH CH ), 2.60 t (2H, ArCH ), 3.19 s [6H, N(CH ) ],
2
2
2
3 2
3.30 t (2H, CH N), 5.26 s (1H, OH), 6.99 s (2H,
2
1
H
). IR spectrum, , cm : 3640 (OH), 954 (NO).
arom
Found, %: C 74.46, H 10.95, N 4.24.
C19H33NO2.
Calculated, %: C 74.21, H 10.81, N 4.56.
CONCLUSIONS
N, N-Dimethyl-3-(3,5-di-tert-butyl-4-hydroxy-
phenyl)propylamine N-oxide XVII was also pre-
pared by oxidation of 2.0 g (6.9 mmol) of amine IX
with 1.5 ml (10.3 mmol) of an 80% solution of cu-
(1) N,N-Dialkyl- -[4-hydroxy(methoxy)aryl]alkyl-
amines of various structures, forming structurally re-
lated series, and their N-oxides were prepared.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 78 No. 5 2005

786
IN, % iodine
DYUBCHENKO et al.
3. US Patent 3305483.
4. EP Patent 500336.
5. US Patent 3202711.
6. EP Patent 474403.
7. US Patent 5281623.
8. Klein, C.D.P., Klingmuller, M., Schellinski, C., et al.,
J. Med. Chem., 1999, no. 42, pp. 3874 3888.
9. Kandalintseva, N.V., Dyubchenko, O.I., Prosen-
ko, A.E., et al., Khim.-Farm. Zh., 2001, vol. 35, no. 3,
pp. 22 25.
10. Kandalintseva, N.V., Dyubchenko, O.I., Terakh, E.I.,
et al., Khim.-Farm. Zh., 2002, vol. 36, no. 4, pp. 13
15.
11. Comprehensive Organic Chemistry. The Synthesis and
Reactions of Organic Compounds, Barton, D. and
Ollis, W.D., Eds., vol. 2: Nitrogen Compounds,
Oxford: Pergamon, 1979.
12. Prilezhaeva, E.N., Reaktsiya Prilezhaeva: Elektrofil’-
noe okislenie (Prilezhaev Reaction: Electrophilic
Oxidation), Moscow: Nauka, 1974.
t, min
Kinetic curves of oxidation of lard. Inhibitor: (1) none,
(2) amine XX, (3) Ionol, and (4) amine IX. (PN) Peroxide
number and (t) time.
(2) The aminoalkylphenols synthesized, owing to
the bifunctional mechanism of the antioxidative effect
and the occurrence of intramolecular synergism, sur-
pass in the inhibiting activity commercial antioxidants
and show promise as inhibitors preventing oxidation
of fat-containing products.
13. USSR Inventor’s Certificate no. 362825.
14. US Patent 4247480.
15. Dyubchenko, O.I., Prosenko, A.E., Terakh, E.I., et al.,
Nauch. Vestn. Tyumensk. Med. Akad., 2003, no. 1,
pp. 23 26.
16. Gershanov, F.B., Gurvich, Ya.A., Dolidze, V.O., et al.,
Prom st. Sint. Kauchuka, 1973, no. 12, pp. 7 9.
17. Voigt, J., Die Stabilisierung der Kunststoffe gegen
Licht und Warme, Berlin: Springer, 1966.
18. Ingibirovanie protsessov okisleniya polimerov smesya-
mi stabilizatora (Inhibition of Polymer Oxidation with
Mixtures of Stabilizers), Moscow: NIITEKhIM, 1970.
19. Emanuel’, N.M. and Lyaskovskaya, Yu.N., Tormozhe-
nie protsessov okisleniya zhirov (Inhibition of Fat
Oxidation), Moscow: Pishchepromizdat, 1961.
(3) The inhibiting activity of the aminoalkylphen-
ols synthesized increases with an increase in the dis-
tance between the nitrogen atom and aromatic core,
decrease in the length of N-alkyl substituents, and
increase in the extent of steric shielding of the phenol-
ic OH group; in going from aminoalkylphenols to the
corresponding N-oxides, the antioxidative activity
decreases.
20. Farsaliev, V.M., Fernando, W.S., and Skott, G., Eur.
Polym. J., 1978, vol. 14, no. 10, pp. 785 788.
ACKNOWLEDGMENTS
21. Skott, G. and Tusoff, M., Eur. Polym. J., 1980,
The authors are grateful to the Russian Foundation
for Basic Research for the access to the STN Interna-
tional database (project no. 00-03-32721) through the
Novosibirsk STN Center, Novosibirsk Institute of
Organic Chemistry, Siberian Division, Russian Acad-
emy of Sciences.
vol. 16, no. 6, pp. 497 501.
22. Terakh, E.I., Prosenko, A.E., Nikulina, V.V., and Zai-
tseva, O.V., Zh. Prikl. Khim., 2003, vol. 76, no. 2,
pp. 261 265.
23. Roginskii, V.A., Fenol’nye antioksidanty: Reaktsion-
naya sposobnost’ i effektivnost’ (Phenolic Antioxi-
dants: Reactivity and Performance), Moscow: Nauka,
1988.
REFERENCES
24. USSR Patent 1376511.
25. Zinov’ev, A.A., Khimiya zhirov (Chemistry of Fats),
1. US Patent 5814695.
2. US Patent 5340369.
Moscow: Pishchepromizdat, 1952.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 78 No. 5 2005