Hydrazines in the synthesis of 1,5,3-dithiazepane and 1,5,3-dithiazocane derivatives in the presence of catalysts under the action of d- and f-elements

Article abstract of DOI:10.1134/S1070428014020080

A method of synthesis was developed for 1,5,3-dithiazepan(dithiazocan)-3- ylamines and 3,3'-bi-1,5,3-dithiazepane(dithiazocane) by hydrazines cyclocondensation with formaldehyde and α,ω-alkanedithiols (1,2-ethanedithiol, 1,3-propanedithiol) involving catalysts based on d- and f-elements.

Full text of DOI:10.1134/S1070428014020080

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 2, pp. 187−190. © Pleiades Publishing, Ltd., 2014.
Original English Text © N.N. Makhmudiyarova, R.Sh. Rakhimov, A.G. Ibragimov, U.M. Dzhemilev, 2014, published in Zhurnal Organicheskoi Khimii, 2014,
Vol. 50, No. 2, pp. 198−200.
Hydrazines in the Synthesis of 1,5,3-Dithiazepane
and 1,5,3-Dithiazocane Derivatives in the Presence
of Catalysts under the Action of d- and f-Elements
N. N. Makhmudiyarova, R. Sh. Rakhimov, A. G. Ibragimov, and U. M. Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia
е-mail: ink@anrb.ru
Received July 31, 2013
Abstract—A method of synthesis was developed for 1,5,3-dithiazepan(dithiazocan)-3-ylamines and 3,3'-bi-
1,5,3-dithiazepane(dithiazocane) by hydrazines cyclocondensation with formaldehyde and α,ω-alkanedithiols
(1,2-ethanedithiol, 1,3-propanedithiol) involving catalysts based on d- and f-elements.
DOI: 10.1134/S1070428014020080
Dithiazepanes [1, 2] and dithiazocanes [3] based on
hydrazines are potential fungicides [1, 2]. The hydrazine
heterocyclization with 1,2-ethanedithiol and formalde-
hyde depending on pH of environment and reaction tem-
perature leads to the formation of a mixture of 1,5,3-di-
thiazepan-3-ylamine and 3,3'-bi-1,5,3-dithiazepane in an
overall yield ~90% [1].
Among the tested catalyst the highest activity was
shown by Cp2TiCl2 in whose presence heterocycle I was
formed in 95% yield (0.5 h, 20°С, solvent toluene) (see
the table). At the ratio hydrazine–formaldehyde–1,2-
ethane-dithiol 1 : 4 : 2 under the same conditions 3,3'-bi-
1,5,3-dithiazepane (II) was formed selectively in ~100%
yield.
With the goal of developing a selective preparation
method for N-substituted 1,5,3-dithiazepanes and
1,5,3-dithiazocanes and also aiming at the extension of
the above method to the reactions with other substituted
hydrazines and alkanedithiols we investigated the
hydrazines cyclocondensation with formaldehyde
and α,ω-alkanedithiols in the presence of catalysts
underlain by transition and rare earth metals. The
preliminary experiments showed that the reaction of
hydrazine with СН2О and 1,2-ethanedithiol at the
molar ratio 1 : 2 : 1 (20°С, 2.5 h) in the presence of
catalysts based on salts and complexes of Cu, Pd, Fe,
Co, Sm, V, Ti, Zr, Mn led to the selective formation of
1,5,3-dithiazepan-3-ylamine (I) (Scheme 1).
In subsequent experiments we tried to synthesize
1,5,3-dithiazocane derivatives by the cyclocondensation
of hydrazine with formaldehyde and 1,3-propanedithiol.
Under the chosen conditions (0.5 h, toluene, 20°С, hydra-
zine–СН2О–1,3-propanedithiol, 1 : 2 : 1) in the presence
of 5 mol % of Cp2TiCl2 1,5,3-dithiazocan-3-ylamine
(III) was formed in 87% yield. At the ratio hydrazine–
СН2О–1,3-propanedithiol 1 : 4 : 2 under the same con-
ditions 3,3'-bi-1,5,3-dithiazocane (IV) was obtained in
80% yield. The attempts to carry out the reaction without
catalyst were unsuccessful.
1
In the Н NMR spectrum of 1,5,3-dithiazocan-3-
ylamine (III) the methylene protons SCH2N resonate
Scheme 1.
( )n
SH
[M]
( )n
2
HS
S
S
S
S
S
4CH2O
2CH2O
HS
SH
NH2NH2
N NH2
N N
( )n
S
I, III
( )n
[M]
( )n
II, IV
n = 1 (I, II), 2 (III, IV).
187

MAKHMUDIYAROVA et al.
The effect of catalyst nature, solvent, and reaction duration on the yield of 1,5,3-dithiazepan-3-ylamine (I)
188
Catalyst, 5 mol % Time, h (solvent)
Yield, %
Catalyst, 5 mol %
Cp2TiCl2
Time, h (solvent)
Yield, %
CuCl
CuCl
CuCl2
CuCl2
CuI
0.5 (toluene)
2.5 (–)
91
83
85
79
87
80
90
85
20
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
0.5 (toluene)
95
73
69
66
65
64
60
50
57
.
Sm(NO3)3 6H2O
0.5 (toluene)
2.5 (–)
CoCl2
Cp2ZrCl2
Fe(acac)3
Co(acac)2
MnCl2
0.5 (toluene)
2.5 (–)
CuI
CuBr
CuBr
–
0.5 (toluene)
2.5 (–)
VO(acac)2
PdCl2
0.5 (toluene)
as a singlet at 4.33 ppm; a triplet at 2.73 ppm. Multi-
plet at 1.55–1.61 ppm correspond to the protons of the
SCH2CH2СН2S fragment. In the 13С NMR spectrum of
heterocycle III the signals of the carbon atoms appear at
54.16, 30.29, and 26.00 ppm.
phenyl, 2,4-nitrophenyl, 4-methylphenyl, benzyl)-1,5,3-
dithiazepan-3-ylamines Vc–Vg in 60–77% yields. In the
same conditions the cyclocondensation of methyl- and
tert-butylhydrazines with CH2O and 1,3-propanedithiol
afforded N-methyl- and N-tert-butyl-1,5,3-dithiazocan-3-
ylamines (VIа, VIb) in 53 and 49% yield respectively. In
the reaction with benzyl-, phenyl-, 4-nitrophenyl-, 2,4-di-
nitrophenyl-, 4-methylphenylhydrazines we obtained
N-substituted 1,5,3-dithiazocan-3-ylamines VIc–VIg in
59–87% yields (Scheme 2).
The attempts of selective thermal cyclocondensa-
tion of alkylhydrazines with formaldehyde and α,ω-
alkanedithiols failed [1]. In this connection we studied
this reaction in the presence of catalysts based on d- and
f-elements. Methyl- and tert-butylhydrazines in the
presence of 5 mol % of Cp2TiCl2 catalyst undergo the
cyclocondensation with formaldehyde and 1,2-ethanedi-
thiol (5 mol % of Cp2TiCl2, 0.5 h, toluene, 20°С) giving
N-alkyl-substituted 1,5,3-dithiazepan-3-ylamines Vа,
Vb in 40 and 55% yields (Scheme 2). N-Methyl- and N-
tert-butyl-1,5,3-dithiazepane-3-ylamines (Vа, Vb) were
obtained in higher yields at the use as catalysts of CoCl2
(60 and 62%) and Fe(acac)3 (59 and 63%).
The probable mechanism of hydrazines heterocycliza-
tion in the presence of a catalyst includes a cycloconden-
sation of α,ω-dithiol with formaldehyde [4], the opening
of the formed 1,3,7-oxadithiocane, nucleophilic addition
of hydrazine to carbocation, and intramolecular cycliza-
tion furnishing the target heterocycles [5–8].
EXPERIMENTAL
By analogy with alkylhydrazines we carried out the
cyclocondensation of aryl(benzyl)hydrazines with form-
aldehyde and 1,2-ethanedithiol (5 mоl% of Cp2TiCl2,
0.5 h, toluene, 20°С) and obtained N-aryl(phenyl, 4-nitro-
The reaction progress was monitored by TLC on Silu-
fol W-254 plates, eluent petroleum ether–EtOAc–CHCl3,
5 : 1 : 1. The reaction products were analyzed by HPLC
on a chromatograph Altex-330 (USA) equipped with an
UV detector on the wavelength 340 nm. NMR spectra
were registered on a spectrometer Bruker Avance 400
[100.62 (13С) and 400.13 MHz (1Н)] in CDCl3. GC-MS
measurements were performed on instruments Finnigan
4021 (glass capillary column 50000 × 0.25 mm, station-
ary phase FTНР-5, carrier gas helium, ramp from 50 to
300°С at a rate 5 deg/min, vaporizer temperature 280°С,
ion source temperature 250°С, EI, 70 eV) and Shimadzu
QP-2010 Plus (capillary column Supelco PTE-5 30000 ×
Scheme 2.
S
[M]
( )n
SH
2CH O
RNH
+
+
N
RNHNH2
2
( )n
HS
S
Vа_Vg, VIа_VIg
R = CH3 (а), (CH3)3C (b), Ph (c), 4-NO2C6H4 (d),
2,4-NO2C6H3 (e), 4-CH3C6H4 (f), C6H5CH2 (g); [M] =
catalyst; n = 1 (V), 2 (VI).
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HYDRAZINES IN THE SYNTHESIS OF 1,5,3-DITHIAZEPANE
189
0.25 mm). Column chromatography was performed on
[C2H4N2]+ (10), 42 [C2H4N]+ (10).
silica gel KSK (100–200 μm). The isolated amines II
are oily liquids well soluble in most organic solvents.
Compounds I, II, Vc, Vg, VIа–VIg were identified by
comparing with known samples [1, 3].
N-Methyl-1,5,3-dithiazepane-3-ylamine (Vа). Yield
60%, Rf 0.58, n 20 1.5151. Н NMR spectrum, δ, ppm:
1
2.55 s (2Н, СН2D), 3.18 с (3Н, СН3), 4.33 s (4Н, СН2).
13С NMR spectrum, δ, ppm: 34.17 (С9), 35.05 (С6,7),
56.36 (С4,2). Mass spectrum, m/z (Irel, %): 164 [M]+
(70), 136 [C3H8N2S2]+ (10), 122 [C3H7NS2]+ (70), 92
[C2H4S2]+ (50), 45 [CH5N2]+ (15).
1,5,3-Dithiazepan(dithiazocan)-3-ylamines, 3,3'-bi-
1,5,3-dithiazepane and 3,3'-bi-1,5,3-dithiazocane.
Heterocyclization of hydrazine hydrate with CH2O and
1,2-ethanedithiol (1,3-propanedithiol). Into a Schlenk
vessel placed on a magnetic stirrer was charged under
an argon atmosphere 20 mmol of formaldehyde and
10 mmol of 1,2-ethanedithiol (1,3-propanedithiol) at
20°С, the mixture was stirred for 30 min, 5 mL of tolu-
ene, 0.5 mmol of an appropriate catalyst, and 10 mmol
of hydrazine hydrate was added, the reaction mixture
was stirred for 30 min at 20°С. The reaction products
were extracted into chloroform, the extract was dried
with CaCl2. On distilling off the solvent the residue was
chromatographed on a column.
N-Aryl(benzyl, alkyl)-1,5,3-dithiazepan(dithiazo-
can)-3-ylamines. Heterocyclization of phenyl(benzyl,
alkyl)hydrazines with CH2O and 1,2-ethanedithiol
(1,3-propanedithiol). Into a Schlenk vessel placed on a
magnetic stirrer was charged under an argon atmosphere
20 mmol of formaldehyde and 10 mmol of 1,2-ethanedi-
thiol (1,3-propanedithiol) at 20°С, the mixture was stirred
for 30 min, 5 ml of toluene, 0.5 mmol of catalyst, and
10 mmol of an appropriate phenyl(benzyl,alkyl)hydrazine
was added, the reaction mixture was stirred for 30 min at
20°С. The reaction products were extracted into chloro-
form, the extract was dried with CaCl2. On distilling off
the solvent the residue was chromatographed on a column.
N-tert-Butyl-1,5,3-dithiazepane-3-ylamine (Vb).
Yield 62%, Rf 0.67, n 20 1.5146. Н NMR spectrum, δ,
1
ppm: 1.13 s (9Н, СН3D), 3.03 s (2Н, СН2), 4.57 s (4Н,
СН2). 13С NMR spectrum, δ, ppm: 30.35 (С10–12),
34.98 (С6,7), 57.00 (С4,2), 45.76 (C9). Mass spectrum,
m/z (Irel, %): 206 [M]+ (50), 160 [C7H16N2S]+ (40), 136
[C3H8N2S2]+ (50), 122 [C3H7NS2]+ (15), 92 [C2H4S2]+
(20), 45 [CH5N2]+ (50).
N-(4-Nitrophenyl)-1,5,3-dithiazepane-3-ylamine
(Vd). Yield 65%, Rf 0.59, nD20 1.5540. 1Н NMR spectrum,
δ, ppm: 3.15 s (4Н, СН2), 4.43 s (4Н, СН2), 6.84–7.02 m
(4Н, СН). 13С NMR spectrum, δ, ppm: 34.75 (С6,7),
56.96 (С4,2), 117.39 (С10,14), 121.30 (С11,12), 139.09 (С12),
146.55 (С9). Mass spectrum, m/z (Irel, %): 269 [M]+ (30),
225 [C9H11N3O2S]+ (100), 92 [C2H4S2]+ (20), 78 [C6H6]+
(15), 46 [CH2S]+ (65).
N-(2,4-Dиnitrophenyl)-1,5,3-dithiazepane-3-
ylamine (Ve). Yield 65%, Rf 0.64, nD20 1.5656. 1Н NMR
spectrum, δ, ppm: 3.20 s (4Н, СН2), 4.38 s (4Н, СН2),
6.80–7.10 m (3Н, СН). 13С NMR spectrum, δ, ppm: 35.43
(С6,7), 57.18 (С4,2), 112.40 (С14), 118.94 (С11), 120.13
(С10), 123.13 (С13), 137.96 (С12), 144.00 (С9). Mass
spectrum, m/z (Irel, %): 316 [M]+ (40), 273 [C9H11N4O4S]+
(40), 244 [C7H7N4O4S]+ (30), 92 [CH2SCH2S]+ (100),
46 [CH2S]+ (50).
N-(4-Methylphenyl)-1,5,3-dithiazepane-3-ylamine
(Vf). Yield 70%, Rf 0.66, n 20 1.5560. 1Н NMR spectrum,
δ, ppm: 1.44 s (3Н, СН3),D3.15 s (4Н, СН2), 4.49 s (4Н,
СН2), 6.87–7.25 m (4Н, СН). 13С NMR spectrum, δ, ppm:
26.23 (С15), 34.12 (С6,7), 58.34 (С4,2), 114.26 (С11,13),
121.15 (С10,14), 145.00 (С9), 149.77 (С12). Mass spectrum,
m/z (Irel, %): 256 [M]+ (70), 197 [C10H15N2S]+ (30), 140
[C7H8NS]+ (15), 121 [C7H9N2]+ (50), 92 [CH2SCH2S]+
(80), 46 [CH2S]+ (50).
1,5,3-Dithiazocan-3-ylamine (III). Yield 87%,
Rf 0.55, nD20 1.5144. Н NMR spectrum, δ, ppm: 1.55–
1
1.61 m (2Н, СН2), 2.73 t (2Н, СН2, J 5.2 Hz), 3.71 s (2Н,
NН2), 4.33 s (2Н, СН2). 13С NMR spectrum, δ, ppm:
26.00 (С7), 30.29 (С6,8), 54.16 (С4,2). Mass spectrum,
m/z (Irel, %): 164 [M]+ (50), 120 [C4H8S2]+ (80), 73
[N2CH2S]+ (50), 60 [NCHS]+ (100), 55 [C2H3N2]+ (25),
27 [NCH]+ (45).
3,3'-Bi-1,5,3-dithiazocane (IV). Yield 80%, Rf 0.60,
nD20 1.5161. Н NMR spectrum, δ, ppm: 1.63–1.81 m
1
ACKNOWLEDGMENTS
(4Н, СН2), 2.45 t (4Н, СН2, J 6.0 Hz), 4.67 s (8Н,
СH2). 13С NMR spectrum, δ, ppm: 29.15 (С7,13), 35.48
(C6,8,14,12), 58.75 (C2,4,10,16). Mass spectrum, m/z (Irel, %):
296 [M]+ (30), 148 [С5Н10NS2]+ (70), 135 [C4H9NS2]+
(50), 120 [C4H8S2]+ (15), 60 [NCH2S]+ (80), 57
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grants
nos. 11-03-00101-а, 11-03-97011-р_Povolzhiye _а).
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