Hydrazines in the synthesis of N-substituted 1,5,3-dithiazocan-3-amines catalyzed by Ti and Cu compounds

Article abstract of DOI:10.1134/S1070428013050023

Efficient preparation method was developed for N-aryl(benzyl, alkyl)-1,5,3-dithiazocan-3-amines consisting in the transamination of 3-tert-butyl-1,5,3-dithiazocane with aryl(benzyl)hydrazines, and also in the reaction of N ¹,N ¹,N

Full text of DOI:10.1134/S1070428013050023

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 655−657. © Pleiades Publishing, Ltd., 2013.
Original English Text © N.N. Makhmudiyarova, K.I. Prokof’ev, L.V. Mudarisova, A.G. Ibragimov, U.M. Dzhemilev, 2013, published in Zhurnal Organicheskoi
Khimii, 2013, Vol. 49, No. 5, pp. 674−676.
Hydrazines in the Synthesis of N-Substituted
1,5,3-Dithiazocan-3-amines
Catalyzed by Ti and Cu Compounds
N. N. Makhmudiyarova, K. I. Prokof’ev, L. V. Mudarisova,
A. G. Ibragimov, and U. M. Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia
e-mail: ink@anrb.ru
Received July 15, 2012
Abstract—Efficient preparation method was developed for N-aryl(benzyl, alkyl)-1,5,3-dithiazocan-3-amines
consisting in the transamination of 3-tert-butyl-1,5,3-dithiazocane with aryl(benzyl)hydrazines, and also in the
reaction of N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-1,7-diamine with aryl(benzyl, alkyl)hydrazines in the
presence of catalytic amounts of Ti and Cu compounds.
DOI: 10.1134/S1070428013050023
Recently [1] we developed a selective method of
the synthesis of N-aryl-1,5,3-dithiazocanes capable of
exhibiting fungicidal activity [2]consisting in the trans-
amination of 3-tert-butyl-1,5,3-dithiazocane with primary
arylamines in the presence of Sm and Co complexes.
drazine, and tert-butylhydrazine.
In the presence of catalytic quantities of Cp2TiCl2
the reaction of aryl(benzyl)hydrazines with 3-tert-
butyl-1,5,3-dithiazocane (I) [molar ratio aryl(benzyl)-
hydrazine–(I)–Cp2TiCl2 1 : 1 : 0.05, solvent acetonitrile,
20°C, 0.5 h] proceeds selectively to afford N-aryl(benzyl)-
1,5,3-dithiazocan-3-amines IIa–IIe in 68–80% yields
(Scheme 1).
In extension of the previous research and also aiming
at the efficient procedure of the synthesis of N-substituted
1,5,3-dithiazocan-3-amines we studied the transamination
of 3-tert-butyl-1,5,3-dithiazocane by substituted hydra-
zines in the presence of catalysts based on transition met-
als [1]. Among the tested in this reaction catalysts based
on salts and complexes of Fe, Cu, V, Pd, Co, Zr, Hf, Ti
Cp2TiCl2 exhibited the highest activity. The initial hydra-
zines involved into the reaction were phenylhydrazine,
4-nitrophenylhydrazine, 2,4-dinitrophenylhydrazine,
4-methylphenylhydrazine, benzylhydrazine, methylhy-
Without catalyst the yield of compounds IIa–IIe was
less than 40% after 24–48 h; without catalyst prevailing
formation of oligomeric compounds was observed, and
the yield of amines II did not exceed 30%.
It is presumable that the catalytic transamination of
3-tert-butyl-1,5,3-dithiazocane (I) by the substituted
hydrazines includes a stage of the heterocycle opening
under the action of the catalyst, the nucleophilic addition
Scheme 1.
S
S
H
[Ti]
_t-BuNH2
+
RNHNH2 t-Bu
N
N N
R
S
I
S
IIа_IIe
R = Ph (a), 4-NO2C6H4 (b), 2,4-NO2C6H3 (c), 4-CH3C6H4 (d), C6H5CH2 (e).
655

MAKHMUDIYAROVA et al.
656
Scheme 2.
RNHNH2
S
S
II
S
S
S
S
S
S
_cat, _XH2
CH2
X
X
X
CH2
NH
NH
NH
NH
cat
cat
cat
R
R
Scheme 3.
S
[Cu]
_ (CH3)2NH
H
R
N
N
+
RNHNH2
N
S
S
N
IIа_IIg
S
R = Ph (a), 4-NO2C6H4 (b), 2,4-NO2C6H3 (c), 4-CH3C6H4 (d), C6H5CH2 (e), CH3 (f), (CH3)3C (g).
of the hydrazine to the carbocation followed by intramo-
lecular cyclization with the formation of N-substituted
1,5,3-dithiazocan-3-amine II (Scheme 2).
79–85% (Scheme 3).
The structure of N-aryl(benzyl, alkyl)-1,5,3-dithiazo-
can-3-amines was confirmed by 13C and 1H NMR spectra
and the other physicochemical methods.
We failed to bring into the reaction under the chosen
conditions the N-alkylhydrazines (methyl-, tert-butylhy-
drazine) for the preparation of the corresponding N-alkyl-
substituted 1,5,3-dithiazocan-3-amines.
EXPERIMENTAL
The reaction progress was monitored by TLC on
Silufol 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 a UV detector at the wavelength 340 nm. 13C and
1H NMR spectra were registered on a spectrometer Bruker
Avance 400 (100.62 and 400.13 MHz respectively), sol-
vent CDCl3. GC-MS measurements were carried out on
instruments Finnigan-4021 (glass capillary column 5000 ×
0.25 mm, stationary phase HP-5, carrier gas helium, ramp
from 50 to 300°C at a rate 5 deg/min, vaporizer tempera-
ture 280°C, ion source temperature 250°C, 70 eV) and
Shimadzu QP-2010 Plus (capillary column Supelco PTE-5
In order to develop the preparation procedure for N-al-
kyl-substituted 1,5,3-dithiazocan-3-amines we carried out
under the catalysis with the complexes of transition metals
the reaction of cyclothiomethylation of alkylhydrazines
with N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-1,7-di-
amine [3] similarly to the reaction of the cyclothiomethyl-
ation of carboxylic acids hydrazides [4]. In the reaction of
N1,N1,N7,N7-tetramethyl-2,6- dithiaheptane-1,7-diamine
with methylhydrazine without catalyst (60°C, CHCl3, 1 h)
the yield of N-methyl-1,5,3-dithiazocan-3-amine (IIf) did
not exceed 15%, and in the presence of 5 mol% of CuCl2
the yield of amine IIf attained 74%. Under the developed
conditions (60°C, CHCl3, 5 mol% CuCl2, 1 h) from
N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-1,7-diamine
and tert-butylhydrazine we obtained N-tert-butyl-1,5,3-
dithiazocan-3-amine (IIg) in ~70% yield.
30 m × 0.25 mm). For column chromatography silica gel
KSK (100–200 μm) was utilized.
N-Aryl(benzyl)-1,5,3-dithiazocan-3-amines. a. In a
Schlenk vessel was placed 10 mmol of 3-tert-butyl-1,5,3-
dithiazocinane [1] and 0.5 mmol of catalyst Cp2TiCl2, the
mixture was stirred for 15–30 min, 5 ml of acetonitrile and
10 mmol of an appropriate aryl(benzyl)hydrazine, was
added, the reaction mixture was stirred for 3 h at 20°C.
In the subsequent experiments we applied the devel-
oped method of alkylhydrazines cyclothiomethylation
with the use of N1,N1,N7,N7-tetramethyl-2,6-dithiahep-
tane-1,7-diamine to the synthesis of N-aryl(benzyl)-1,5,3-
dithiazocanes II and we obtained them in the yields of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

HYDRAZINES IN THE SYNTHESIS OF N-SUBSTITUTED 1,5,3-DITHIAZOCAN-3-AMINES
657
(C11,13), 145.59 (C9). Mass spectrum, m/z (Irel, %): 254
[M]+ (100), 209 [C11H17N2S]+ (50), 152 [C8H10NS]+ (30),
121 [C7H9N2]+ (70), 92 [CH2SCH2S]+ (20), 46 [CH2S]+
(50). Mcalc 254.41.
The reaction products were passed through a thin bed of
SiO2, the solvent was distilled off on the rotary evaporator.
b. In a Schlenk vessel was placed 10 mmol of
N1,N1,N7,N7-tetramethyl-2,6-dithiaheptane-1,7-diamine,
10 mmol of aryl(benzyl, alkyl)hydrazine, 5 ml of chlo-
roform, 0.5 mmol of catalyst CuCl2, the mixture was
stirred for 1 h at 60°C. The reaction products were passed
through a thin bed of SiO2, the solvent was distilled off
on the rotary evaporator.Amines II are brown oily fluids,
well soluble in the most organic solvents .
N-Benzyl-1,5,3-dithiazocan-3-amine (IIe). Yield
1
80% (a), 81% (b), Rf 0.43, oily fluids. H NMR spectrum,
δ, ppm: 1.93 s (2H, CH2), 2.68 s (2H, CH2), 4.55 s (2H,
CH2), 4.69 s (2H, CH2), 6.88–7.55 m (5H, CH). 13C NMR
spectrum, δ, ppm: 29.13 (C7), 33.69 (C6,8), 59.41 (C2,4),
69.20 (C9), 125.27 (C13), 127.92 (C11,15), 129.30 (C12,14),
143.80 (C10). Mass spectrum, m/z (Irel, %): 254 [M]+
(100), 182 [C9H14N2S]+ (40), 135 [C8H12N2]+ (80), 92
[CH2SCH2S]+ (15), 46 [CH2S]+ (100). Mcalc 254.42.
N-Phenyl-1,5,3-dithiazocan-3-amine (IIa). Yield
1
71% (a), 79% (b), Rf 0.55, oily fluids. H NMR spec-
trum, δ, ppm: 1.87 s (2H, CH2), 2.80 s (2H, CH2), 4.51 s
(2H, CH2), 6.80–7.33 m (5H, CH). 13C NMR spectrum,
δ, ppm: 29.01 (C7), 35.07 (C6,8), 59.74 (C4,2), 119.20
(C10,14), 120.28 (C12), 125.75 (C11,13), 145.64 (C9). Mass
spectrum, m/z (Irel, %): 240 [M]+ (60); 147 [C4H7N2S2]+
(50), 120 [C3H6NS2]+ (100), 106 [C6H6N2]+ (15), 91
[C6H5N]+ (35), 77 [C6H5]+ (23), 75 [CH3N2S]+ (25),
60 [CH2NS]+ (25), 51 [CNCN]+ (50), 46 [CH2S]+ (10).
Mcalc 240.39.
N-Methyl-1,5,3-dithiazocan-3-amine (IIf). Yield
1
74% (b), Rf 0.47, oily fluids. H NMR spectrum, δ, ppm:
1.81 s (2H, CH2), 4.35 s (3H, CH3), 2.43 s (2H, CH2),
4.01 s (2H, CH2). 13C NMR spectrum, δ, ppm: 29.03 (C7),
37.85 (C6,8), 59.56 (C2,4), 45.24 (C9). Mass spectrum,
m/z (Irel, %): 178 [M]+ (70), 233 [C5H13N2S]+ (20), 105
[C3H9N2S]+ (50), 45 [CH5N2]+ (70). Mcalc 178.32.
N-tert-Butyl-1,5,3-dithiazocan-3-amine (IIg). Yield
N-(4-Nitrophenyl)-1,5,3-dithiazocan-3-amine (IIb).
1
74% (b), Rf 0.53, oily fluids. H NMR spectrum, δ, ppm:
1
Yield 68% (a), 83% (b), mp 198–200OC. H NMR spec-
1.13 s (9H, CH3), 1.77 s (2H, CH2), 2.85 s (2H, CH2),
4.15 s (2H, CH2). 13C NMR spectrum, δ, ppm: 28.32
(C7), 35.44 (C6,8), 50.35 (C11–13), 58.46 (C2,4), 45.24
(C10). Mass spectrum, m/z (Irel, %): 220 [M]+ (50), 161
[C7H17N2S]+ (50), 133 [C5H13N2S]+ (70), 87 [C4H11N2]+
(100). Mcalc 220.40.
trum, δ, ppm: 1.74 s (2H, CH2), 2.55 s (2H, CH2), 4.83 s
(2H, CH2), 6.54 d (2H, CH, J 4 Hz), 7.02 d (2H, CH,
J 4 Hz). 13C NMR spectrum, δ, ppm: 28.92 (C7), 33.81
(C6,8), 58.66 (C4,2), 118.19 (C10,14), 122.59 (C11,13), 140.09
(C12), 147.71 (C9). Mass spectrum, m/z (Irel, %): 285 [M]+
(40), 198 [C7H8N3O2S]+ (15), 226 [C9H12N3O2S]+ (100),
272 [C10H14N3O2S2]+ (20), 92 [CH2SCH2S]+ (20), 78
[C6H6]+ (15), 46 [CH2S]+ (65). Mcalc 285.38.
ACKNOWLEDGMENTS
N-(2,4-Dinitrophenyl)-1,5,3-dithiazocan-3-amine
The study was carried out under the financial support
of the Russian Foundation for Basic Research (grants nos.
11-03-00101-a, 11-03-97011-p_Volga region_a).
1
(IIc). Yield 75% (a), 80% (b), mp 203–205OC. H NMR
spectrum, δ, ppm: 1.91 s (2H, CH2), 2.70 s (2H, CH2),
4.56 s (2H, CH2), 6.90–7.13 m (3H, CH). 13C NMR
spectrum, δ, ppm: 27.50 (C7), 36.00 (C6,8), 60.10 (C2,4),
113.41 (C14), 119.24 (C11), 123.13 (C12), 139.69 (C10),
145.00 (C9). Mass spectrum, m/z (Irel, %): 330 [M]+ (40),
287 [C10H13N4O4S]+ (40), 272 [C9H11N4O4S]+ (20), 244
[C7H7N4O4S]+ (50), 92 [CH2SCH2S]+ (10), 46 [CH2S]+
(100). Mcalc 330.39.
REFERENCES
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N-(4-Methylphenyl)-1,5,3-dithiazocan-3-amine
(IId). Yield 78% (a), 85% (b), Rf 0.67, oily fluids.
1H NMR spectrum, δ, ppm: 1.50 s (3H, CH3), 2.00 s (2H,
CH2), 2.95 s (2H, CH2), 4.69 s (2H, CH2), 6.97–7.35 m
(4H, CH). 13C NMR spectrum, δ, ppm: 19.23 (C15), 29.32
(C7), 32.92 (C6,8), 59.43 (C2,4), 112.41 (C10,14), 119.15
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013