Aminomethoxy derivatives of benzylsulfanylheptane

Article abstract of DOI:10.1134/S1070427210110157

Synthesis and structure of new aminomethoxy derivatives of 1-benzylsulfanylheptane by the Mannich condensation of 1-benzylsulfanylheptan-2- ol, formaldehyde, and secondary amines were studied.

Full text of DOI:10.1134/S1070427210110157

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2010, Vol. 83, No. 11, pp. 1973−1977. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.G. Mamedbeili, I.A. Dzhafarov, K.A. Kochetkov, T.G. Kyazimova, Kh.I. Gasanov, O.B. Gadzhieva, 2010, published in Zhurnal
Prikladnoi Khimii, 2010, Vol. 83, No. 11, pp. 1841−1845.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Aminomethoxy Derivatives of Benzylsulfanylheptane
E. G. Mamedbeili, I. A. Dzhafarov, K. A. Kochetkov, T. G. Kyazimova,
Kh. I. Gasanov, and O. B. Gadzhieva
Azerbaijani Pedagogical University, Baku, Azerbaijan
Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, Baku, Azerbaijan
Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russia
Received March 1, 2010
Abstract—Synthesis and structure of new aminomethoxy derivatives of 1-benzylsulfanylheptane by the Mannich
condensation of 1-benzylsulfanylheptan-2-ol, formaldehyde, and secondary amines were studied.
DOI: 10.1134/S1070427210110157
Organic compounds containing various functional
groups and heteroatoms, such as sulfur and nitrogen (or
both together), are widely used as effective biologically
active substances and pharmaceutical preparations, as
well as additives improving the quality of oils and fuels
[1–3]. A directed synthesis of these compounds used in
various chemical industries is a rather topical task not
only for development of synthetic organic chemistry,
but also for applied research. In this context, syntheses
of new compounds of this kind from accessible raw
materials by improved methods continue to attract
researchers’ attention [4–6]. The Mannich reaction is
an important and promising way to obtain sulfur- and
nitrogen-containing compounds [7–9].
In continuation of previous studies concerned with
nitrogen-containing alkyl(aryl) sulfanyl alkanes [10–
14], we report here results obtained in synthesis of
aminomethoxy derivatives of 1-benzyl sulfanyl heptane
and analysis of their properties. For this purpose, we first
synthesized the previously unknown sulfur-containing
secondary alcohol, 1-benzyl sulfanyl heptan-2-ol (III)
by reacting benzylthiol (I) with 1-bromoheptan-2-ol (II)
by Scheme 1.
The secondary thioalcohol (III) was synthesized by
reacting equimolar amounts of the starting components
I and II in an alkaline medium (40% aqueous solution
of NaOH) at a temperature of 50–60°C in the course of
3–4 h. The yield of the target product was 72%.
Further, we used the Mannich condensation of
1-benzyl sulfanyl heptan-2-ol (III) with formaldehyde
in the presence of secondary amines (IV)–(VIII) to
obtain amino derivatives of 1-benzyl sulfanyl heptane,
(IX)–(XIII), by Scheme 2.
Aminomethoxy derivatives of 1-benzyl sulfanyl
heptane, (IX)–(XIII), were synthesized at 50–60°C
in the course of 3–4 h at the equimolar ratio between
the starting components. In this case, the yield of the
reaction products was 72–78%.
The thus synthesized 1-benzyl sulfanyl heptan-
2-ol (III) and its amino derivatives (IX)–(XIII) are
transparent liquids with characteristic odors. They are
insoluble in water, but can be well dissolved in ethanol,
Scheme 1.
C6H5CH2
NaOH
C6H5CH2SH + Br
50_60°C
+ NaBr + H2O.
S
OH
OH
III
II
I
1973

1974
MAMEDBEILI et al.
Scheme 2.
HNR2
1
3
5
7
CH2
2
4
6
IV, V
S
CH2
O
NR2
III + CH2O
IX, X
Z
NH
Bn
S
VI_VIII
O
N
Z
XI_XIII
R = C2H5 (IV), (IX); C4H9 (V), (X); Z = CH2 (VI), (XI); O (VII), (XII); (CH2)2 (VIII), (XIII).
acetone, benzene, and chloroform. The physicochemical
characteristics of III, IX–XIII are listed in Tables 1 and
2, together with the elemental analysis data for these
compounds.
750–730 cm–1.
The 1H NMR spectra of the compounds synthesized
are typical and also confirm the above structure. In the
1H NMR spectrum of secondary alcohol III, the proton
of the hydroxy group appears as a multiplet at 2.7 ppm.
In the spectra of compounds III and IX–XIII, protons
of methyl groups (CH3) appear as a multiplet at 0.90–
1.0 ppm. Protons of methylene groups (CH2) give signals
at 1.5–1.7 ppm in the form of a multiplet. To protons of
SCH2 (C1) groups belong signals observed at 2.5 ppm as
a triplet. Protons of the OCH moiety (C2) appear at 3.4–
3.7 ppm as a triplet, and protons of the OCH2N moiety,
at 4.2–4.3 ppm as a doublet of doublets. The signals
observed at 3.9 ppm as a singlet are characteristic of
protons of CH2 groups in the benzyl moiety (PhCH2).
Protons of the phenyl moiety give downfield signals:
protons in the para-position at 7.30 ppm, two protons
in the meta-position at 7.34 ppm, and two protons in the
ortho-position at 7.36 ppm as a multiplet.
The purity of the starting and synthesized compounds
and the composition of the reaction mixtures was
monitored by GLC. The structure of the target products
was determined by elemental analysis, IR and 1H NMR
spectroscopies, and mass spectrometry. The IR spectrum
of compound III shows an absorption band at 3500 cm–
1, which is characteristic of the hydroxy group and is
not observed in the corresponding spectra of compounds
IX–XIII. For all the compounds, we observed absorption
bands at 795–730 cm–1 (characteristic of the C–S bond),
1220–1200 cm–1 (C–N bond), and 2940–2930 and
2880–2850 cm–1 (stretching vibrations of the C–H bond
and CH3 and CH2 groups, respectively). The vibrations
νCH of the benzene ring appear at 3030–3080 cm–1 as a
medium-intensity band. The spectra of compounds IX–
XIII contain strong absorption bands associated with
out-of-plane deformation vibrations of the C–H band at
The mass spectra (electron impact ionization)
of compounds III and IX–XIII show signals of the
Table 1. Physicochemical characteristics of compounds III and IX–XIII
bp, °С
(1–3
Compound
nD20
d420
Yield, %
mm Hg)
1-Benzyl sulfanyl heptan-2-ol (III)
160–162
175–177
188–190
182–184
188–190
190–192
1.5360
1.5210
1.4984
1.5250
1.5246
1.5246
1.0205
0.9711
0.9392
1.0014
1.0322
0.9965
72
75
78
73
74
75
1-Benzyl sulfanyl-2-(N,N-diethylaminomethoxy)heptane (IX)
1-Benzyl sulfanyl-2-(N,N-dibutylaminomethoxy)heptane (X)
1-Benzyl sulfanyl-2-piperidinomethoxyheptane (XI)
1-Benzyl sulfanyl-2-morpholinomethoxyheptane (XII)
2-Benzyl sulfanyl-2-(N-hexamethyleniminomethoxy)heptane (XIII)
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 83 No. 11 2010

AMINOMETHOXY DERIVATIVES OF BENZYLSULFANYLHEPTANE
1975
Table 2. Elemental analysis and molecular refraction data for compounds III and IX–XIII
Found, %
Found
Compound Calculated
Found
Calculated
Calculated, %
Formula
C14H22OS
MRD
M
C
H
N
S
III
IX
–
72.84
72.97
70.38
70.56
9.26
9.31
13.38
13.45
239
238.39
99.97
100.21
70.10
70.28
10.22
10.28
4.30
4.33
9.85
9.91
C19H33NOS
C23H41NOS
C20H33NOS
C19H31NO2S
C21H35NOS
324
323.54
X
118.57
118.75
72.54
72.76
10.82
10.88
3.66
3.69
8.39
8.44
380
379.61
XI
102.69
102.81
71.26
71.59
9.85
9.91
4.14
4.17
9.49
9.55
336
335.55
XII
XIII
100.15
100.03
67.38
67.61
9.20
9.26
4.12
4.15
9.44
9.50
338
337.53
107.44
107.46
71.82
72.15
10.03
10.09
3.98
4.01
9.12
9.17
350
349.58
corresponding molecular ions and products of their
fragmentation. The mass spectrum of the starting sulfur-
containing alcohol (III) is characterized by the following
set of fragments: 238 (27%) [M+], 221 (100%) M–OH,
207 (9%) / M–OH–CH2, 138 (72%) /C8H10S, and 122
(6%) / C7H6S.
Aminomethoxy derivatives of benzyl sulfanyl
heptane, IX–XIII, were tested as antimicrobial
additives. The tests were made in an M-11 oil [GOST
(State Standard) 9-052–75].
As test cultures served fungal (Aspergillus niger,
Candida tropicalis) and bacterial (Pseudomonas
aeruginosa) cultures. The results obtained are presented
in Table 3.
The mass spectra of compounds IX–XIII show
signals of the corresponding molecular ions and products
of their fragmentation.
The test results demonstrated that, under certain
Table 3. Results of tests of compounds IX–XIII as antimicrobial additives to lubricant oils for the example of M-11 oil
Diameter of the microorganism growth suppression zone, mm
Compound
Concentration, %
fungi
Pseudomonas aeruginosa
bacteria
Aspergillus niger Candida tropicalis
Additive to M-11 oil:
IX
0.5
1
0.5
1
22
42
22
42
20
38
18
31
18
34
20
38
X
XI
0.5
1
0.5
1
0.5
1
16
30
16
30
18
34
18
34
18
34
18
34
18
34
18
34
20
36
XII
XIII
8-Oxyquinoline (reference)
M-11 oil (without additives)a
0.5
1
+
14
34
+
12
26
+
14
32
+
a (+) stands for heavy growth of microorganism around a lunula in a Petri dish.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 83 No. 11 2010

1976
MAMEDBEILI et al.
conditions (0.5–1.0 wt %), the compounds suppress
growth of microorganisms. It can be seen in Table 3 that
compounds IX and XIII show the highest efficiency.
Their antimicrobial activity exceeds that of the industrial
additive 8-oxyquinoline, taken as a reference. The rest
of the compounds show results close to that of the
reference. It was found that, at a content of 0.5–1.0 wt %
of these compounds, there are no negative changes in
the service parameters of oils, and their antiseptic effect
is long preserved at higher humidities and temperatures.
Compounds IX–XIII exert no adverse influence on the
physicochemical properties of oils. These compounds
were also tested as antimicrobial preparations in
medicine.
was washed with water to a neutral reaction and dried
over MgSO4. After the solvent was evaporated, the
residue was distilled in a vacuum. A 43-g portion (72%)
of 1-benzyl sulfanyl heptan-2-ol (III) was obtained:
bp 160–162°C (1 mm Hg), nD20 1.5360, d420 1.025;
MRD 72.84, calculated 72.97. IR spectrum, ν, cm–1: 3500
1
(OH), 2930 (CH3), 2850 (CH2), 735 (C–S). H NMR
spectrum, δ, ppm: 0.9 t (3H, CH3), 2.75 s (1H, OH),
2.4 m (2H, SCH2), 3.4 t (1H, OCH), 3.8 s (2H, PhCH2),
7.30–7.36 t (5H, C6H5). Found (%): C 70.38, H 9.26,
S 13.38. C14H22OS. Calculated (%): C 70.56, H 9.31,
S 13.45.
General procedure for synthesis of aminomethoxy
derivatives of 1-benzyl sulfanyl heptane, (IX)–(XIII).
To a solution of 4.76 g (0.02 mol) of 1-benzyl sulfanyl
heptan-2-ol (III) in 30 ml of benzene was added under
agitation a solution of 0.6 g (0.02 mol) of formaldehyde
in 10 ml of benzene. Then, a solution of 0.02 mol of
a freshly distilled amine, (IV)–(VII) in 10 ml of
benzene was added dropwise to this mixture at room
temperature. The agitation was continued for 1 h at the
same temperature, and then for 3–4 h at 50–60°C. After
the mixture cooled, the solvent was evaporated and the
residue was distilled in a vacuum. The physicochemical
parameters, yield, and spectral characteristics of the
compounds thus synthesized are listed in Tables 1 and 2.
EXPERIMENTAL
The IR spectra were recorded with a UR-20
spectrophotometer in the range 4000–400 cm–1, and
the 1H NMR spectra, with a Bruker WP-400 instrument
(400 MHz, CDCl3 as solvent), with the chemical shifts
given relative to TMS. The mass spectra were obtained
on a G-7070E mass spectrometer at an ionizing voltage
of 70 eV.
The reaction mixtures were subjected to an chromato-
graphic analysis and the purity of the compounds
synthesized with an LKhM-80 MD chromatograph
[300 × 3 mm steel column; 5% polyethylene glycol
succinate on Dynachrom P phase; carrier-gas helium
(40 cm3 min–1); catharometer as detector; column and
evaporator temperatures 155 and 230°C, respectively].
CONCLUSIONS
(1) 1-Benzyl sulfanyl heptan-2-ol was synthesized in
72% yield by reacting benzylthiol with 1-bromoheptan-
2-ol in an alkaline medium at a temperature of 50–60°C.
The effect of compounds IX–XIII on the anti-
microbial properties of M-11 oil were studied with
their solutions in this oil used in concentrations of 0.5–
1.0%. The antimicrobial properties were determined
in a hygrothermal chamber by the lunula method.
Experiments were carried out at a temperature of 28–
30°C in the course of 2 to 3 days. Fungal and bacterial
cultures were used as test organisms.
(2) The Mannich condensation of 1-benzyl sulfanyl
heptan-2-ol, formaldehyde, and secondary amines at 50–
60°C in the course of 3–4 h gives previously unknown
aminomethoxy derivatives of 1-benzyl sulfanyl heptane
in 73–78% yield.
(3) Aminomethoxy derivatives of 1-benzyl sulfanyl
heptane effectively suppress growth of microorganisms
in M-11 oil in concentrations of 0.5–1.0%.
1-Benzyl sulfanyl heptan-2-ol (III). To a mixture
of 31 g (0.25 mol) of benzylthiol (I) and 25 g of a 40%
solution of an alkali [solution of 10 g (0.25 mol) of
NaOH in 15 g of water] was added dropwise under
agitation 48.75 g of 1-bromopentan-2-ol (II) at 50–
60°C. The agitation was continued for 3–4 h at the
same temperature. After the mixture cooled, 15 ml of
a 5% NaOH solution was added. The organic layer was
separated, 30 ml of benzene was added, the mixture
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