Catalytic Synthesis of N-Aryl-1,5,3-dithiazocanes

Article abstract of DOI:10.1134/S107042802003029X

Abstract: An efficient procedure has been developed for the synthesis of N-aryl-1,5,3-dithiazocanes and1,1′-biphenylenebis(1,5,3-dithiazocanes) by heterocyclization of N¹,N¹,N⁷,N⁷-tetramethyl-2,6-dithiaheptane-1

Full text of DOI:10.1134/S107042802003029X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 3, pp. 544–547. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 3, pp. 475–479.
SHORT
COMMUNICATIONS
Catalytic Synthesis of N-Aryl-1,5,3-dithiazocanes
E. B. Rakhimovaa,*, I. V. Ozdena, and A. G. Ibragimova
a Institute of Petrochemistry and Catalysis, Ufa Federal Research Center, Russian Academy of Sciences,
Ufa, 450075 Russia
*e-mail: rakhimovaelena@mail.ru
Received October 15, 2019; revised January 13, 2020; accepted January 20, 2020
Abstract—An efficient procedure has been developed for the synthesis of N-aryl-1,5,3-dithiazocanes and
1,1′-biphenylenebis(1,5,3-dithiazocanes) by heterocyclization of N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-
1,7-diamine with aromatic amines or 4,4′-methylene(or sulfonyl)dianiline in the presence of Sm(NO3)3·6H2O as
catalyst.
Keywords: catalysis, heterocyclization, dithiaheptanediamine, arylamines, 1,5,3-dithiazocanes
DOI: 10.1134/S107042802003029X
Saturated S,N-containing heterocycles are basic
structural fragments of many biologically active
compounds [1–4]. A classical method of synthesis of
N-substituted 1,5,3-dithiazocanes is based on the cy-
clocondensation of primary amines with formaldehyde
and propane-1,3-dithiol [5]. We previously demon-
strated [6] the possibility of obtaining N-substituted
1,5,3-dithiazocanes by catalytic recyclization of 1-oxa-
3,7-dithiocane with primary amines. In continuation
of our studies [7–13] in the field of synthesis of
S,N-containing heterocycles, herein we focused on the
development of an efficient method for the preparation
of practically important N-substituted 1,5,3-dithiazo-
canes. For this purpose, N1,N1,N7,N7-tetramethyl-2,6-
dithiaheptane-1,7-diamine (1) was involved in hetero-
cyclization with primary aromatic amines. Preliminary
experiments showed that the uncatalyzed reaction of
o-aminophenol with an equimolar amount of diamine
in EtOH–CHCl3 (20°C, 3 h) produced less than 15% of
2-(1,5,3-dithiazocan-3-yl)phenol (2). In order to im-
prove the yield of 2, the reaction of 1 with o-amino-
phenol was carried out in the presence of catalysts
based on transition metal and rare earth salts (Ni, Co,
Fe, Cu, Ni, Sm); the yield of 2 increased in the
following series of catalysts: NiCl2·6H2O (32%) <
CoCl2·6H2O (35%) < FeCl3·6H2O (40%) < CuCl2·
6H2O (45%) < Cp2TiCl2 (48%) < SmCl3·6H2O
(55%) < Sm(NO3)3·6H2O (58%). o- and p-Amino-
Scheme 1.
S
S
S
S
S
RNH2
R
N
N
R
R
N
or
S
2–6, 8
7
Me2N
S
S
NMe2
1
S
S
H2N–X–NH2
N
X
N
S
S
9, 10
i: 5 mol % Sm(NO3)3·6H2O, EtOH–CHCl3, room temperature, 3 h.
2, R = 2-HOC6H4 (58%); 3, R = 4-HOC6H4 (66%); 4, R = 3-HOC(O)C6H4 (63%); 5, R = 4-HOC(O)C6H4 (71%); 6, R = 4-HSC6H4
(78%); 7, R = 3-HSC6H4 (45%); 8, R = 1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl (57%); 9, X = methylenebis(1,4-phenylene)
(65%); 10, X = sulfonylbis(1,4-phenylene) (82%).
544

CATALYTIC SYNTHESIS OF N-ARYL-1,5,3-DITHIAZOCANES
545
Heterocyclization of N1,N1,N7,N7-tetramethyl-
2,6-dithiaheptane-1,7-diamine (1) with aromatic
amines and dianilines (general procedure). A mixture
of 0.22 g (1 mmol) [or 0.44 g (2 mmol) in the reactions
with dianilines] of compound 1 [14], 10 mL of chloro-
form, and 0.022 g (0.05 mmol) of Sm(NO3)3·6H2O
was stirred for 30 min at room temperature, and
1 mmol of the corresponding amine or diamine in
10 mL of ethanol was added dropwise. The mixture
was stirred for 3 h at ~20°C and evaporated, and the
residue was purified by silica gel column chroma-
tography.
phenols reacted with an equimolar amount of 1 in
EtOH–CHCl3 in the presence of 5 mol % Sm(NO3)3·
6H2O (20°C, 3 h) to afford 2- and 4-(1,5,3-dithiazocan-
3-yl)phenols 2 and 3, respectively, in 58–66% yields
with high selectivity (Scheme 1). Increase of the
amount of the catalyst to 10 mol % did not lead to
a significant improvement of the yield. The solvent
system ethanol–chloroform was chosen taking into
account good solubility of the initial reactants therein.
The reactions of 1 with isomeric aminobenzoic acids
selectively produced 63–71% of 3- and 4-(1,5,3-di-
thiazocan-3-yl)benzoic acids 4 and 5. Likewise,
4-(1,5,3-dithiazocan-3-yl)benzenethiol (6) was ob-
tained by the heterocyclization of 1 with p-aminoben-
zenethiol under the given conditions. However, the
reaction of 1 with an equimolar amount of m-amino-
benzenethiol followed the [2+2]-cyclocondensation
pathway to form tetrathiadiazacyclohexadecane (7)
whose structure was confirmed by the presence of
the molecular ion peak with m/z 515 [M + H]+ in the
MALDI TOF/TOF mass spectrum. By reacting com-
pound 1 with a heterocyclic amine, 4-amino-1,5-
dimethyl-2-phenyl-1,2-dihydro-3H-pyrazole-3-one, we
obtained 4-(1,5,3-dithiazocan-3-yl)-substituted deriva-
tive 8 in 57% yield.
2-(1,5,3-Dithiazocan-3-yl)phenol (2). Yield 0.14 g
(58%), colorless oil, nD20 = 1.5673, Rf 0.80 (CHCl3–
EtOAc–hexane, 1:5:1). The spectral characteristics of
2 were identical to those reported in [6].
4-(1,5,3-Dithiazocan-3-yl)phenol (3). Yield 0.16 g
(66%), colorless oil, nD20 = 1.6037, Rf 0.85 (PhMe–
EtOAc–Me2CO, 4:1:1). The spectral characteristics of
3 were identical to those reported in [6].
3-(1,5,3-Dithiazocan-3-yl)benzoic acid (4). Yield
0.17 g (63%), colorless crystals, mp 189–191°C, Rf 0.5
(CHCl3–Me2CO, 1:2). 1H NMR spectrum (DMSO-d6),
δ, ppm: 1.66 br.s (2H, 7-H), 2.60 br.s (2H, 6-H, 8-H),
4.85 br.s (4H, 2-H, 4-H); 7.11 br.s (1H), 7.37 br.s
(2H), and 7.43 br.s (1H) (Harom). 13C NMR spectrum
(DMSO-d6), δC, ppm: 28.5 (C6, C8), 32.3 (C7), 55.6
(C2, C4); 114.3, 118.3, 119.4, 129.6, 131.8, 143.8
(Carom); 168.2 (C=O). Mass spectrum: m/z 270
(Irel 100%) [M + H]+. Found, %: C 53.45; H 5.58;
N 5.15; S 23.76. C12H15NO2S2. Calculated, %:
C 53.50; H 5.61; N 5.20; S 23.81.
The results obtained with aromatic amines prompted
us to study heterocyclization of 1 with diamines.
Compound 1 reacted with 4,4′-methylenedianiline and
4,4′-sulfonyldianiline at a ratio of 2:1 under the above
conditions [5 mol % Sm(NO3)3·6H2O, EtOH–CHCl3,
20°C, 3 h] to give 3,3′-[methylenebis(1,4-phenylene)]-
bis(1,5,3-dithiazocane (9) and 3,3′-[sulfonylbis(1,4-
phenylene)]bis(1,5,3-ditiazocane) (10), respectively, in
65–82% yield (Scheme 1).
4-(1,5,3-Dithiazocan-3-yl)benzoic acid (5). Yield
0.19 g (71%), colorless crystals, mp 202–204°C, Rf 0.4
(PhH–EtOH, 9:1). The spectral characteristics of 5
were identical to those reported in [6].
1
The H NMR spectra of compounds 2–6 and 8–10
characteristically showed three signals at δ 1.65–1.84,
2.54–2.72, and 3.84–4.89 ppm due to methylene
protons of the 1,5,3-dithiazocane fragment. The corre-
sponding carbon signals were located in the 13C NMR
spectra at δC 23.5–32.4, 27.9–32.3, and 55.0–57.0 ppm.
The signals were assigned using homo- and hetero-
nuclear correlation techniques. The product structure
was also confirmed by their MALDI TOF/TOF mass
spectra (positive ionization mode) which contained the
molecular ion peaks with expected m/z values.
4-(1,5,3-Dithiazocan-3-yl)benzenethiol (6). Yield
0.20 g (78%), colorless crystals, mp 273–274°C, Rf 0.8
(PhMe–EtOAc–Me2CO, 8:1:1). The spectral character-
istics of 6 were identical to those reported in [6].
3,3′-(1,5,9,13-Tetrathia-3,11-diazacyclohexa-
decane-3,11-diyl)bis(benzenethiol) (7). Yield 0.23 g
(45%), colorless oil, Rf 0.9 (PhH–EtOH, 9:1). 1H NMR
spectrum (CDCl3), δ, ppm: 1.79–1.84 m (4H, 7-H,
15-H), 2.70 br.s (8H, 6-H, 8-H, 14-H, 16-H), 3.51 br.s
(2H, SH), 4.73 br.s (8H, 2-H, 4-H, 10-H, 12-H), 6.70–
6.83 m (6H, 2′-H, 4′-H, 6′-H), 7.10–7.28 m (2H, 5′-H).
13C NMR spectrum (CDCl3), δC, ppm: 29.0 (C6, C8,
C14, C16), 32.0 (C7, C15), 56.5 (C2, C4, C10, C12), 110.9
Thus, Sm(NO3)3·6H2O-catalyzed heterocyclization
of N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-1,7-di-
amine with aromatic amines and dianilines provides
an efficient method of synthesis of N-aryl-1,5,3-dithia-
zocanes and bis(1,5,3-ditihazocanes).
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RAKHIMOVA et al.
546
(C6′), 113.9 (C2′), 119.9 (C4′), 129.8 (C5′), 131.8 (C1′),
143.9 (C3′). Mass spectrum: m/z 515 (Irel 100%)
[M + H]+. Found, %: C 51.28; H 5.84; N 5.37;
S 37.30. C22H30N2S6. Calculated, %: C 51.32; H 5.87;
N 5.44; S 37.37.
was performed using KSK silica gel (100‒200 μm).
Commercially available reagents were purchased from
Sigma–Aldrich and Acros Organics.
ACKNOWLEDGMENTS
4-(1,5,3-Dithiazocan-3-yl)-1,5-dimethyl-2-
phenyl-1,2-dihydro-3H-pyrazole-3-one (8). Yield
0.19 g (57%), colorless oil, nD20 = 1.5557, Rf 0.7
The spectral and analytical data were obtained using the
facilities of the Agidel joint center (Institute of Petro-
chemistry and Catalysis, Ufa Federal Research Center,
Russian Academy of Sciences).
1
(CHCl3–Me2CO, 1:2). H NMR spectrum (CDCl3), δ,
ppm: 1.80–1.83 m (2H, 6-H, 8-H), 2.18–2.22 m
(3H, 5′-CH3), 2.57–2.68 m (4H, 6-H, 7-H, 8-H), 2.95–
2.98 m (3H, 1′-CH3), 4.35–4.39 m (4H, 2-H, 4-H);
7.22 br.s (1H), 7.32 br.s (2H), and 7.38 br.s (2H)
(Harom). 13C NMR spectrum (CDCl3), δC, ppm: 11.0
(CH3), 23.5 (C7), 29.5 (C6, C8), 36.4 (CH3), 55.5
(C2, C4), 119.1, 123.5, 126.3, 129.0, 135.0, 151.7,
163.0 (C=O). Found, %: C 57.22; H 6.26; N 12.49;
S 19.10. C16H21N3OS2. Calculated, %: C 57.28;
H 6.30; N 12.53; S 19.12.
FUNDING
This study was performed in accordance with the
research program of the Institute of Petrochemistry and
Catalysis (Ufa Federal Research Center, Russian Academy
of Sciences; project no. AAAA-A19-119022290010-9 for
2019–2021 “Metal Complex and Heterogeneous Catalysis
in the Synthesis of Macroheterocycles and Heteroatom Com-
pounds”), as well as under financial support by the Ministry
of Science and Education of the Russian Federation (project
no. 2019-05-595-000-058).
3,3′-[Methylenebis(1,4-phenylene)]bis(1,5,3-di-
thiazocane) (9). Yield 0.30 g (65%), colorless crystals,
mp 175–176°C, Rf 0.9 (PhMe–EtOAc–Me2CO, 8:1:1).
The spectral characteristics of 9 were identical to those
reported in [6].
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
REFERENCES
3,3′-[Sulfonylbis(1,4-phenylene)]bis(1,5,3-dithia-
zocane) (10). Yield 0.42 g (82%), colorless crystals,
mp 101–103°C, Rf 0.5 (CHCl3–Me2CO, 1:2). 13C NMR
spectrum (DMSO-d6), δ, ppm: 1.65 br.s (4H, 7-H),
2.60 br.s (8H, 6-H, 8-H), 4.86 br.s (8H, 2-H, 4-H),
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