Synthesis and antioxidant activity of 1-amino-4-phenyl-2-butanethiols

Article abstract of DOI:10.1134/S1070427209090158

1-Amino-4-phenyl-2-butanethiols were synthesized and characterized and their antioxidant activity in auto-oxidation of cumene and in their reaction with cumyl peroxide radicals and cumyl hydroperoxide was studied.

Full text of DOI:10.1134/S1070427209090158

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 9, pp. 1587–1591. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.T. Guseinova, K.I. Alieva, I.A. Rzaeva, A.M. Magerramov, I.A. Aliev, V.M. Farzaliev, M.A. Allakhverdiev, 2009, published in
Zhurnal Prikladnoi Khimii, 2009, Vol. 82, No. 9, pp. 1488–1492.
ORGANIC SYNTHESIS AND INDUSTRIAL
ORGANIC CHEMISTRY
Synthesis and Antioxidant Activity
of 1-Amino-4-phenyl-2-butanethiols
A. T. Guseinova, K. I. Alieva, I. A. Rzaeva, A. M. Magerramov,
I. A. Aliev, V. M. Farzaliev, and M. A. Allakhverdiev
Baku State University, Baku, Azerbaijan
Kuliev Institute of Additive Chemistry, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
Received February 18, 2008
Abstract—1-Amino-4-phenyl-2-butanethiols were synthesized and characterized and their antioxidant activity
in auto-oxidation of cumene and in their reaction with cumyl peroxide radicals and cumyl hydroperoxide was
studied.
DOI: 10.1134/S1070427209090158
A topical task of modern tribochemistry is to
improve the stability of petroleum fuels and oils
against oxidation in prolonged storage and service. The
only way to stabilize fuels and oils is to add antioxi-
dant additives. At present, various alkyl derivatives of
phenols, aromatic amines, aminophenols, various
sulfides, and metal salts of dithio-phosphoric acids are
widely used as antioxidant additives [1].
and amino sulfides can be used to stabilize
polymethacrylic acid under the action of X-rays [2].
Some aminothiols are used as inhibitors of oxidation
and decomposition of organic peroxides and stabilizers
of fats and fat-containing products [3].
In this study, we synthesized 1-amino-4-phenyl-2-
propanethiol and examined the relationship between its
structure and antioxidant activity. As the starting
product served 1-chloro-4-phenyl-2-butanol (I) syn-
thesized by reacting benzylmagnesium chloride with
epichlorohydrin:
Published data on the use of 1,2-aminothiols as
inhibitors of oxidation of fuels and other petroleum
products are scarce. There have been separate reports
that, owing to their antioxidant properties, aminothiols
C6H5CH2CH2CHCH2Cl.
OH
C6H5CH2MgCl + CH2CHCH2Cl
O
The highest yield of 1-chloro-4-phenyl-2-butanol
(I) is obtained at a 1 : 2 ratio between the Grignard
reagent and epichlorohydrin. At a 1 : 1 molar ratio, the
yield of the target product sharply decreases. The
physicochemical constants of 1-chloro-4-phenyl-2-
butanol are consistent with published data [4].
C6H5CH2CH2CH−CH2
I + KOH
O
II
The physicochemical constants of oxirane II we
synthesized are consistent with published data [5].
Finely ground potassium hydroxide in a solution of
anhydrous ether was used to dehydrochlorinate 1,2-
chlorohydrin I and convert it to the corresponding 1,2-
epoxy-4-phenylbutane (II):
1,2-Epithio-4-phenylbutane (III) was synthesized
by anionotropic substitution of the oxygen atom in
oxirane II with a sulfur atom from the thiocarbamide
molecule in the presence of sulfuric acid:
1587

1588
GUSEINOVA et al.
Table 1. Selected physicochemical parameters of 1,2-aminobutanethiols IV–IX
C6CH2CH2−CH−CH2NR2
SH
С
H
N
S
Comp.
no.
Yield,
%
bp.,
(p, mm Hg)
nD20
R
found, %/calculated,%
65
67
110(1)
102(1)
1.5217
1.5240
0.49
0.57
70.70/70.89
9.54/9.70
5.76/5.91
6.04/6.22
13.32/13.50
14.05/14.22
IV
V
69.20/69.39 10.03/10.22
70.12/70.29 10.31/10.46
70
69
120(1)
1.5317
1.5485
0.68
0.47
5.73/5.86
5.49/5.62
13.20/13.39
12.69/12.85
VI
112(0.8)
72.13/72.29
9.09/9.24
VII
75
79
149(0.4)
185(0.1)
1.5618
1.5932
0.55
0.63
71.33/71.49
74.55/74.71
8.79/8.94
7.34/7.39
5.81/5.96
5.32/5.45
13.42/13.62
12.28/12.45
VIII
IX
II + S=C(NH2)2
To reveal a relationship between the structure of the
1,2-aminobutanethiols IV–IX we synthesized and their
antioxidant activity, we obtained a number of phenyl-
substituted 1,2-aminobutanethiols IV–IX by reacting
1,2-epithio-4-phenylbutane III with various amines:
C6H5CH2CH2CH−CH2
S
III
C6H5CH2CH2CH−CH2
S
N
H
NHR2
X
C6H5CH2CH2CH−CH2NHaRb
C6H5CH2CH2CH−CH2−N
X
SH
SH
IV−VI, IX
VΙI, VIII
R = C2H5, a = 0, b = 2 (IV); R = n-C3H7, a = 1, b = 1 (V); R = C(CH)3, a = 1, b = 1 (VI); R = C6H5, a = 1, b = 1 (IX); X =
CH2 (VII); X = O (VIII).
1,2-Aminobutanethiols IV–VI were synthesized by
reacting III with various primary and secondary
amines at a 1 : 2 reagent ratio and 70–80°C in the
course of 5–6 h in a sealed ampule. All the 1,2-
aminobutanethiols IV–IX synthesized are colorless
characterize asymmetric, symmetric, and pulsation
vibrations of the oxirane ring, but there appears a
strong absorption band at 625 cm–1, characteristic of
stretching vibrations of the C–S bond in the three-
membered thiirane ring.
fluids
turning
yellow upon
storage.
The
In the IR spectrum of phenyl-substituted 1,2-
aminobutanethiols IV–IX, we found a very weak band
at 2540–2565 cm–1, which corresponds to stretching
vibrations of the SH bond and cannot sometimes be
detected. In spectra of the compounds synthesized with
secondary amino groups we also observed a strong
absorption band at 3385 cm–1, which characterizes
stretching vibrations of the N–H bond. In addition, all
physicochemical constants of 1-chloro-4-phenyl-2-bu-
tanthiol IV–IX we obtained are listed in Table 1.
The structure of the compounds synthesized was
confirmed by IR and NMR spectroscopies, and their
purity was verified by elemental analysis and TLC.
The IR spectrum of the starting thiirane III contains
no strong bands at 840, 1105, and 1235 cm–1, which
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SYNTHESIS AND ANTIOXIDANT ACTIVITY OF 1-AMINO-4-PHENYL-2-BUTANETHIOLS
1589
the compounds have absorption bands at around 1065 cm–1, n-propylamine, tert-butylamine) or heterocyclic
which are related to the C–N bond. The IR spectra of
all compounds we synthesized contain absorption
bands at 1590–1600 and 1490–1510 cm–1, which can
be attributed to stretching vibrations of C=C bonds in
the aromatic ring.
amine-containing moieties (piperidine, morpholine) in
their molecule have no effect on the initiated oxida-
tion. However, 1,2-aminobutanethiols IX containing a
phenylamine moiety hinder the initiated oxidation of
cumene.
The 1H NMR spectrum of thiirane III, in which the
thiirane ring is separated from the aromatic ring by two
methylene groups, signals of the
The reason is that the NH group in the aliphatic
chain is not involved in chain-termination reactions
and has no effect on the inhibitor efficiency, which
depends in this case only on the SH group. It is known
that thiols show no antioxidant activity by themselves,
with a high antioxidant activity exhibited only when
C6H5NH and SH groups are combined in the same
molecule.
H
C−C
H
S
moiety appear as upfield doublets at 1.85 and 2.25
ppm, which correspond to cis- and trans-protons. It
should be noted that two protons of the methylene
groups bonded to the three-membered thiirane ring
commonly appear as doublets at 2.10 and 2.45 ppm
[4]. The signals of protons of the methylene group
bonded to the aromatic ring, which are commonly
superimposed by multiplet signals of the CH protons,
were found at 2.60–2.75 ppm. In a weak field, protons
of aromatic rings appear as a singlet at 6.85–7.00 ppm.
The duration τ of the induction period was used to
calculate the stoichiometric coefficient f, equal to the
number of oxidation chains terminated at a single
molecule of an inhibitor and its conversion products.
The value of the stoichiometric coefficient f for 1-
phenyl-4-phenylamino-2-butanethiol IX is 2.97. The
rate constant of the reaction, k = 3.12 l mol–1 s–1. It is
known that, in the case f ≥ 1, inhibitors commonly
terminate a single oxidation chain. Because the
molecule of the inhibitor under study contains amine
and sulfhydryl groups, f somewhat exceeds unity.
1
The H NMR spectrum of 1-(N-diethylamino)-4-
phenyl-2-butanethiol (IV) contains signals of six
protons of two methyl groups in the form of a triplet in
its part centered at 1.15 ppm and signals of protons of
the (CH2)2NCH2 moiety as a multiplet at 2.45 ppm.
The signal of the proton of the SH bond was identified
on the basis of changes in the spectrum upon addition
of D2O. The nonequivalent protons of the phenylamine
moiety appear as two triplets at 6.4 and 6.7 ppm.
The reaction of 1-phenyl-4-phenylamino-2-
butanethiol IX with cumyl hydroperoxide was
performed in chlorobenzene in the atmosphere of
nitrogen at a temperature of 110°C. It was found that
compound IX actively decomposes cumyl hydro-
peroxide. It was shown that one molecule of 1-phenyl-
4-phenylamino-2-butanethiol can decompose 15000 mole-
cules of cumyl hydroperoxide.
1
The H NMR spectra of the rest of the phenyl-
substituted 1,2-butanethiols V–IX are similar to the
spectra of compound IV, but, naturally, differ in the
positions of radical signals.
It can be seen in Table 2 that the industrial anti-
oxidant ionol does not decompose cumyl hydro-
peroxide and is inferior in inhibiting activity to 1-
phenyl-4-phenylamino-2-butanethiol because f and k
for ionol are 2.00 and 2.10 M–1 s–1, respectively.
The inhibiting properties of phenyl-substituted 1,2-
butanethiols IV–IX under study were examined in
model reactions (Table 2). As the model reaction
served the reaction of oxidation in a chlorobenzene
solution at 60°C, initiated by α,α-azobisisobutyronitrile
(AIBN). The reaction was monitored by the absorption
of oxygen in a pressure-gage installation with
automatic compensation of the oxygen pressure. The
inhibiting properties of the compounds were examined
in the reaction with cumyl peroxide radicals and cumyl
hydroperoxide.
EXPERIMENTAL
The IR spectra were measured on a Specord 75-IR
1
spectrophotometer, and the H NMR spectra, on a
Bruker-300 MHz instrument. The individuality and the
course of the reactions were monitored by TLC on
Silufol UV-254 plates, with a 3 : 1 mixture of heptane
and isopropanol used as eluent.
Our study demonstrated that phenyl-substituted 1,2-
butanethiols containing alkylamine (e.g., diethylamine,
1-Chloro-4-phenyl-2-butanol (I). An ether
solution of benzylmagnesium chloride, produced from
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GUSEINOVA et al.
Table 2. Kinetic parameters of reaction of compound IX with cumyl peroxide (CP) radicals (60°C [AIBN] = 2×10–2 M) and
with cumyl hydroperoxide (CHP) (110°C) and induction period durations for auto-oxidation of cumene in the presence of this
compound (110°C, [InH] = 5×10–5 M)
CP radicals
CHP
k×10–4,
Comp. no.
Formula
τ, min
f
k, M–1
ν
M–1
CH2CH2CH−CH2−NH
2.97
3.12
11.8
15000
250
IX
SH
OH
t-Bu
Bu-t
Ionol
2.00
2.10
–
150
CH3
63 g (0.5 mol) of benzyl chloride, 12 g of magnesium,
2–3 small iodine crystals, and 30 ml of dry ether, was
cooled with ice and a solution of 32.5 g (1 mol) of
epichlorohydrin in 200 ml of dry ether was added
dropwise under agitation. Then the reaction mixture
was heated under permanent agitation at 35°C for
additional 2 h. After that, with the flask cooled with
ice, a hydrochloric acid solution (10%) was added to
the reaction mixture until two transparent layers were
formed. The upper organic layer was separated and the
aqueous layer was three times extracted with ether.
The ether extracts were combined, washed with a
dilute soda solution and water, and dried over
anhydrous sodium sulfate. After the solvent was
evaporated, the reaction product was subjected to
vacuum distillation to give 71 g (71%) of compound I,
bp 161–162°C at 22 mm Hg, nD20 = 1.5354 (published
data [5]: bp 158–160°C at 23 mm Hg, nD20 = 1.537).
of the acid in 350 ml of water). The reaction mixture
was cooled under vigorous agitation to 5–10°C and
29.6 g (0.2 mol) of 1,2-epoxy-4-phenylbutane II was
added dropwise at this temperature in the course of
30 min. Upon addition of oxirane, the reaction mixture
was agitated for 1 h at room temperature and
neutralized with 21.2 g (0.2 mol) of sodium carbonate
dissolved in 10 ml of water. The aqueous layer was
separated from the organic layer and extracted with dry
ether (2 × 50 ml). The ether extracts were combined
with the organic layer and dried over anhydrous
sodium sulfate. After the ether was evaporated,
vacuum distillation yielded 25 g (76%) of compound
III, bp 120°C at 2.5 mm Hg, nD20 = 1.5625, Rf = 0.82.
Found, %: C 73.31; H 7.12; S 19.16. C10H12S.
Calculated, %: C 73.12; H 7.35; S 19.52.
IR spectrum, ν, cm–1: 625, 750, 1930. H NMR
spectrum, CCl4, δ, ppm: 2.75 t (2H, ArCH2), 1.85 d
1
and 2.25 d (2H, 6H2S), 6.85–7.00 m (5H, C6H5).
1,2-Epoxy-4-phenylbutane (II). To a solution of
18.5 g (0.1 mol) of 1-chloro-4-phenyl-2-butanol I in
50 ml of dry diethyl ether we added 11.2 g (0.2 mol) of
finely ground potassium hydroxide (with a strong
warming-up of the reaction mixture observed). Then
the mixture was heated on a water bath for 1.5 h. After
the mixture was cooled, the ether layer was discharged
and the residue was thrice extracted with dry diethyl
ether. The ether was evaporated and the reaction
product was distilled under a normal pressure to give
11.5 g (75%) of compound II, bp 115–116°C at 20 mm
Hg (published data [6]: bp 106–109°C at 17 mm Hg).
1-Diethylamino-4-phenyl-2-butanethiol (IV). A
mixture of 16.4 g (0.1 mol) of 1,2-epithio-4-phenyl-
butane III and 14.6 g (0.2 mol) of diethylamine was
heated in a sealed ampule at 80–90°C for 6 h. Then the
ampule was cooled, opened, and the excess amount of
diethylamine was distilled off in a vacuum of the water-
jet pump. Vacuum distillation yielded 13 g of
20
compound IV, bp 110°C at 1 mm Hg, nD = 1.5217,
Rf = 0.49. Found, %: C 70.51; H 9.89; N 5.73; S 13.85.
C14H23NS. Calculated, %: C 70.83; H 9.76; N 5.90; S
13.51.
1,2-Epithio-4-phenylbutane (III). A three-necked
flask was charged with 15.2 g (0.2 mol) of thio-
carbamide and 6 ml of a sulfuric acid solution (1 equiv
In a similar way, we synthesized aminothiols V and
VI, whose physicochemical constants are listed in
Table 1.
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SYNTHESIS AND ANTIOXIDANT ACTIVITY OF 1-AMINO-4-PHENYL-2-BUTANETHIOLS
1591
4-Phenyl-1-phenylamino-2-butanethiol (IX). To
a solution of 9.3 g (0.1 mol) of aniline in 20 ml of
benzene, cooled to 10°C, we added 8.2 g (0.05 mol) of
1,2-epithio-4-phenylbutane III in the course of 1 h in
such a way that the temperature of the reaction mixture
did not exceed 10°C. After the addition of thiirane IV
was complete, the temperature of the reaction mixture
was raised first to room temperature and then, on a
water bath, to 70–75°C, and the mixture was kept at
this temperature for 3 h. Then the solvent was
evaporated and the reaction product was subjected to
vacuum distillation to give 10 g of compound IX, bp
185°C at 1 mm Hg, nD20 = 1.5932, Rf = 0.63. Found, %:
C 70.18; H 7.16; N 5.24; S 11.48. C16H19NOS.
Calculated, %: C 70.29; H 7.00; N 5.12; S 11.73.
of various phenyl-substituted 1,2-aminobutanethiols,
was developed.
(2) It was shown that 1-phenyl-4-phenylamino-2-
butanethiol is a complex type inhibitor, which
terminates oxidation chains and catalytically
decomposes cumyl hydroperoxide.
REFERENCES
1. Kuliev, A.M., Khimiya i tekhnologiya prisadok k
maslam i toplivam (Chemistry and Technology of
Additives to Oils and Fuels), Leningrad: Khimiya, 1985.
2. Rachinskii, F.Yu. and Slachevskaya, N.M., Khimiya
aminotiolov (Chemistry of Aminothiols), Leningrad:
Khimiya, 1965.
3. USSR Inventor’s Certificate, no. 118934.
4. Allakhverdiev, M.A., Farzaliev, V.M., and Khalilo-
va, A.Z., Zh. Org. Khim., 1984, vol. 20, no. 6, p. 1350.
5. Malinovskii, M.S., Okisi olefinov i ikh proizvodnykh
(Oxides of Olefins and Their Derivatives), Moscow:
Khimiya, 1961.
Aminothiols VII and VIII were synthesized in a
similar way.
CONCLUSIONS
6. Levi, J. and Sfiras, Y., Comp. Rend., 1927, vol. 184,
p. 1335.
(1) A method for synthesis of 1,2-epithio-4-
phenylbutane, which is a key compound for production
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