Effective synthesis of N-substituted 1,3,5-dithiazinanes by reactions of N-methyl-1,3,5-dithiazinane and 1,3,5-trithiane with aromatic amines

Article abstract of DOI:10.1134/S1070428011090065

A novel procedure has been developed for selective synthesis of N-aryl-1,3,5-dithiazinanes, 1,2,6,7-tetrahydro-3,5,1,7-benzodithiadiazonine, and 6,7-dihydro-1,3,5,7-benzotrithiazonine by reactions of aniline derivatives with N-methyl-1,3,5-dithiazinane or 1,3,5-trithiane in the presence of transition and rare earth metal salts and complexes. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011090065

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1300–1304. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © E.B. Rakhimova, I.V. Vasil’eva, L.M. Khalilov, A.G. Ibragimov, U.M. Dzhemilev, 2011, published in Zhurnal Organicheskoi
Khimii, 2011, Vol. 47, No. 9, pp. 1283–1287.
Effective Synthesis of N-Substituted 1,3,5-Dithiazinanes
by Reactions of N-Methyl-1,3,5-dithiazinane and 1,3,5-Trithiane
with Aromatic Amines
E. B. Rakhimova, I. V. Vasil’eva, L. M. Khalilov, A. G. Ibragimov, and U. M. Dzhemilev
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received February 23, 2011
Abstract—A novel procedure has been developed for selective synthesis of N-aryl-1,3,5-dithiazinanes,
1,2,6,7-tetrahydro-3,5,1,7-benzodithiadiazonine, and 6,7-dihydro-1,3,5,7-benzotrithiazonine by reactions of
aniline derivatives with N-methyl-1,3,5-dithiazinane or 1,3,5-trithiane in the presence of transition and rare
earth metal salts and complexes.
DOI: 10.1134/S1070428011090065
N-Substituted 1,3,5-dithiazinanes are widely used
as selective sorbents for noble and rare metals [1],
fungicides [2], biocides [3, 4], and food additives
[5, 6]; a popular method of their synthesis is based on
cyclothiomethylation of primary amines with formal-
dehyde–hydrogen sulfide [7]. This reaction was
studied in detail with the use of various aliphatic and
aromatic amines [8]. Its considerable disadvantage is
the necessity of using gaseous hydrogen sulfide and
aqueous formaldehyde. Moreover, most reactions are
characterized by low selectivity. For example, the
condensation of o-phenylenediamine with H2S–CH2O
(Scheme 1) gives a mixture of compounds I–IV which
are difficult to separate [9]. Analogous reaction with
m-phenylenediamine gives rise to a mixture of various
macroheterocyclic compounds, whereas p-phenylene-
diamine failed to react with H2S–CH2O under similar
conditions [8].
phenylenediamines, aminophenols, and aminobenzene-
thiols with N-methyl-1,3,5-dithiazinane and 1,3,5-tri-
thianes as synthetic equivalents of H2S and CH2O.
Preliminary experiments showed that, among Fe, Co,
Ti, Zr, Ni, Pd, Sm, and Yb salts and complexes used as
catalysts, the most efficient in the reactions of aromatic
amines with N-methyl-1,3,5-ditihazinane were CoCl2
and Sm(NO3)3·6H2O. Therefore, all subsequent exper-
iments were carried out in the presence of these
catalysts.
o-Phenylenediamine reacted with an equimolar
amount of N-methyl-1,3,5-ditihazinane in the presence
of 5 mol % of CoCl2 (CHCl3, 20°C, 3 h) to produce
1,2,6,7-tetrahydro-3,5,1,7-benzodithiadiazonine (I)
with high selectivity (yield 75%). The reaction of
p-phenylenediamine with N-methyl-1,3,5-dithiazinane,
catalyzed by Sm(NO3)3 ·6H2O (DMF, 60°C, 3 h), in-
volved only one amino group with formation of
4-(1,3,5-dithiazinan-5-yl)aniline (V) in 70% yield.
Analogous reaction with m-phenylenediamine resulted
in the formation of poorly soluble substances. The
With a view to develop an ecologically safe and
efficient procedure for the synthesis of N-substituted
1,3,5-dithiazinanes we examined reactions of isomeric
Scheme 1.
CH2
N
H
N
HN
NH2
S
S
N
3 h
+
6CH2O
+
4H2S
+
+
+
S
CH2
N
H
NH2
N
N
H
HN
I, 16%
II, 51%
III, 18%
IV, 15%
1300

EFFECTIVE SYNTHESIS OF N-SUBSTITUTED 1,3,5-DITHIAZINANES
1301
Scheme 2.
OH
S
OH
S
S
[Sm]
[Sm]
+
N
N
S
Me
NH2
OH
VI, 72%
S
S
S
+
HO
N
N
S
Me
H2N
VII, 91%
Scheme 3.
M
N
S
S
N
S
S
H
M
H
H
HO
N
+
–MeNH2
N
S
S
··
HO
Me
HO
H
··
A
VII
N
Me
yield of heterocyclic compounds I and V in the ab-
1,3,5-dithiazinane molecule [10–12]. As a result, the
reaction of N-methyl-1,3,5-dithiazinane with arylamine
with formation of N-aryl-1,3,5-dithiazinane occurs
more readily (Scheme 3). In fact, in the 13C NMR
spectra we observed upfield shift (ΔδC = –0.84 ppm)
of the signal from the carbon atom linked to the coor-
dinated nitrogen atom in complex A relative to the
corresponding signal of p-aminophenol. No analogous
shift of the C–N carbon signal was observed in the
13C NMR spectrum for N-methyl-1,3,5-dithiazinane.
sence of a catalyst did not exceed 10%.
1
In the H NMR spectrum of V, methylene protons
in the 1,3,5-dithiazinane ring resonated as broadened
singlets at δ 4.25 (SCH2S) and 4.97 ppm (SCH2N).
Signals from aromatic protons were observed in the
region δ 6.7–7.7 ppm. Triplet signals at δC 34.30 and
55.40 ppm in the 13C NMR spectrum of V were
assigned to the methylene carbon atoms in the 1,3,5-di-
thiazinane ring located, respectively, between two
sulfur atoms and between sulfur and nitrogen atoms.
Isomeric o- and p-aminophenols reacted with
N-methyl-1,3,5-dithiazinane in the presence of 5 mol %
of Sm(NO3)3·6H2O (EtOH–CHCl3, 60°C, 3 h) to give
2- and 4-(1,3,5-dithiazinan-5-yl)phenols VI and VII in
72 and 91% yield, respectively (Scheme 2).
Cyclothiomethylation of o- and p-aminophenols
with H2S–CH2O yields 1,3,5-dithiazinanes in a mixture
with 1,2,4-trithiolane [13]. Chemoselectivity of this
reaction is determined by the reactant concentrations in
the initial three-component mixture. Under these con-
ditions, supply of a required amount of gaseous hydro-
gen sulfide is fairly difficult to control; as a result,
1,2,4-trithiolane is obtained as by-product. Likewise,
1,2,4-trithiolane is formed together with the target
products in the reactions of o- and p-aminobenzene-
thiols with CH2O–H2S.
Presumably, the above reactions catalyzed by sa-
marium complex involve coordination of the substrate
to the metal ion, which enhances mobility of NH hy-
drogen atoms in the aromatic amine molecule and
favors activation of the C–S bond in the N-methyl-
Scheme 4.
S
S
SH
S
S
[Sm]
+
N
S
Me
NH2
SH
HN
VIII
S
S
S
[Sm]
+
HS
N
N
S
Me
H2N
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

RAKHIMOVA et al.
1302
Scheme 5.
NH2
NH2
NH2
HN
S
S
S
S
H2N
H2N
N
HN
I, 67%
V, 60%
OH
OH
OH
N
S
S
S
S
NH2
[Fe]
[Fe] H2N
HO
N
S
S
S
VI, 58%
VII, 78%
SH
SH
S
S
S
S
S
NH2
H2N
HS
N
HN
VIII, 62%
IX, 65%
1
However, 6,7-dihydro-1,3,5,7-benzotrithiazonine
(VIII) and 4-(1,3,5-dithiazinan-5-yl)benzenethiol (IX)
were synthesized with high selectivity in 70 and 75%
yield, respectively, by reactions of o- and p-amino-
benzenethiols with N-methyl-1,3,5-dithiazinane
(Scheme 4) in the presence of Sm(NO3)3 ·6 H2O as
catalyst (EtOH–CHCl3, 60°C, 3 h).
In the H NMR spectrum of IX, the broadened singlet
at δ 4.25 ppm was assigned to protons in the methylene
group linked to two sulfur atoms. Protons in the two
NCH2S groups in the dithiazinane ring gave rise to
a broadened singlet at δ δ 4.93 ppm. Signals at
δC 33.23 and 55.02 ppm in the 13C NMR spectrum of
IX originated from C2 and C4/C6 in the dithiazinane
ring, respectively.
The IR spectrum of compound VIII contained
an absorption band at 1580 cm–1 due to N–H bending
vibrations in the secondary amino group, whereas no
absorption at 2550–2600 cm–1, typical of SH group
was present. Compound VIII displayed in the
1H NMR spectrum three broadened singlets with equal
intensities at δ 3.86, 4.56, and 4.85 ppm due to methyl-
ene protons located between two sulfur atoms and
between nitrogen and sulfur atoms, respectively. In the
13C NMR spectrum of VIII we observed two signals at
δC 33.10 and 50.56 ppm (SCH2S) and one signal at
δC 55.73 ppm (NCH2S). Aromatic carbon nuclei reso-
nated at δC 108.65, 119.98, 122.06, 125.25, 127.40,
and 145.57 ppm. These findings allowed us to assign
the structure of 6,7-dihydro-1,3,5,7-benzotrithiazonine
to compound VIII.
Our results obtained by studying reactions of
aromatic amines with N-methyl-1,3,5-dithiazinane, as
well as the possibility for replacement of the latter by
more commercially accessible 1,3,5-trithiane, stimulat-
ed our study on the reactions of 1,3,5-trithiane with
isomeric phenylenediamines, aminophenols, and
aminobenzenethiols in the presence of the above listed
transition metal salts and complexes.
Isomeric phenylenediamines, aminophenols, and
aminobenzenethiols reacted with an equimolar amount
of 1,3,5-trithiane to give 1,2,6,7-tetrahydro-3,5,1,7-
benzodithiadiazonine (I), 4-(1,3,5-dithiazinan-5-yl)-
aniline (V), 2- and 4-(1,3,5-dithiazinan-5-yl)phenols
VI and VII, 6,7-dihydro-1,3,5,7-benzotrithiazonine
(VIII), and 4-(1,3,5-dithiazinan-5-yl)benzenethiol (IX)
with high selectivity (Scheme 5). In these reactions,
FeCl3·6H2O showed the highest catalytic activity. The
presence of 5 mol % of that catalyst ensured 58–78%
yield of heterocycles I and V–IX in acetonitrile at
60°C (reaction time 6 h).
Compound IX showed in the IR spectrum strong
absorption bands at 720, 1100, 1600, and 2900 cm–1,
which correspond to stretching vibrations of the C–S,
C–N, C=Carom, and C–H (CH2) bonds, and a weak
band at 2600 cm–1, typical of S–H bond, was present.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

EFFECTIVE SYNTHESIS OF N-SUBSTITUTED 1,3,5-DITHIAZINANES
1303
Presumably, as in N-methyl-1,3,5-dithiazinane, the
nitrogen atom in aromatic amine molecule is coor-
dinated to the central metal ion of the catalyst
(FeCl3 ·6H2O), which enhances lability of the N–H
bond in the initial arylamine and favors [10] hydrogen
transfer from aromatic amine to activated trithiane
with formation of compounds I and V–IX (Scheme 3).
(3H, CH3), 4.12 br.s (2H, 2-H), 4.42 br.s (4H, 4-H,
6-H). 13C NMR spectrum, δC, ppm: 32.00 q (CH3),
37.63 t (C2), 59.38 t (C4, C6).
Cyclothiomethylation of aromatic amines with
N-methyl-1,3,5-dithiazinane (general procedure).
A Schlenk flask equipped with a magnetic stirrer was
charged under argon with 11 mmol of N-methyl-1,3,5-
dithiazinane in 5 ml of chloroform, 0.5 mmol of the
catalyst [Sm(NO3)3·6H2O or CoCl2], and 10 mmol of
the corresponding arylamine in 5 ml of CHCl3, DMF,
or EtOH. The mixture was stirred for 3 h at a required
temperature (20 or 60°C). Compounds I, VI, and VII
were identified by comparing with authentic samples
[9, 13].
Thus catalytic reaction of N-methyl-1,3,5-dithia-
zinane or 1,3,5-trithiane with o- and p-phenylenedi-
amines, aminophenols, and aminobenzenethiols en-
sures selective preparation of N-substituted 1,3,5-di-
thiazinanes, 1,2,6,7-tetrahydro-3,5,1,7-benzodithiadia-
zonine, and 6,7-dihydro-1,3,5,7-benzotrithiazonine in
high yields without using gaseous hydrogen sulfide
and aqueous formaldehyde.
4-(1,3,5-Dithiazinan-5-yl)aniline (V). Rf 0.6
(benzene–ethanol, 9:1). IR spectrum, ν, cm–1: 3300,
1
EXPERIMENTAL
2900, 1650, 1600, 1100, 720. H NMR spectrum, δ,
ppm: 4.25 br.s (2H, 2-H), 4.97 br.s (4H, 4-H, 6-H),
6.70 d (2H, 8-H, 12-H), 7.70 d (2H, 9-H, 11-H).
13C NMR spectrum, δC, ppm: 34.3 t (C2), 55.4 t (C4,
C6), 115.4 d (C8, C12), 116.6 d (C9, C11). Mass spec-
trum: m/z 213.379 [M + H]+. C9H12N2S2. M 212.3371.
The IR spectra were recorded on a Specord 75IR
spectrometer from samples dispersed in mineral oil.
The mass spectrum of V was obtained on a Bruker
Autoflex III MALDI-TOF/TOF mass spectrometer.
1
The H and 13C NMR spectra were measured from
6,7-Dihydro-1,3,5,7-benzotrithiazonine (VIII).
solutions in CDCl3 on a Bruker Avance 400 spectrom-
eter at 400.13 and 100.62 MHz, respectively, using
Bruker standard pulse sequences. The progress of
reactions was monitored by TLC on Silufol UV-254
plates; spots were visualized by treatment with iodine
vapor. The products were analyzed by HPLC on
an Altex-330 chromatograph (USA) equipped with
a UV detector (λ 340 nm). Gas chromatographic–mass
spectrometric analysis of compounds VIII and IX was
performed on Finnigan 4021 (glass capillary column,
50000×0.25 mm, stationary phase HP-5, carrier gas
helium, oven temperature programming from 50 to
300°C at a rate of 5 deg/min, injector temperature
280°C, ion source temperature 250°C; electron impact,
70 eV) and Shimadzu QP-2010Plus instruments
(Supelco PTE-5 capillary column, 30 m×0.25 mm).
Silica gel KSK (100–200 μm) was used for column
chromatography.
Rf 0.4 (benzene–ethyl acetate, 5:1). IR spectrum, ν,
1
cm–1: 3400, 2900, 1620, 1580, 1110, 720. H NMR
spectrum, δ, ppm: 3.86 br.s (2H, 2-H), 4.56 br.s (2H,
9-H), 4.85 br.s (2H, 4-H), 6.59–7.12 m (4H, 10-H,
11-H, 12-H, 13-H). 13C NMR spectrum, δC, ppm:
33.10 t (C2), 50.56 t (C9), 55.73 t (C4), 108.65 d (C10),
119.98 d (C12), 122.06 d (C11), 125.25 d (C13), 127.40 s
(C7), 145.57 s (C6). Mass spectrum, m/z (Irel, %): 197
(35) [M – S]+, 169 (20) [M – CH2SCH2]+, 137 (10)
[M – CH2SCH2S]+, 136 (100) [M – CH3SCH2S]+, 109
(35) [M – SPh]+. Found, %: C 47.25; H 4.90; N 6.15;
S 41.70. C9H11NS3. Calculated, %: C 47.12; H 4.83;
N 6.11; S 41.94. M 229.
4-(1,3,5-Dithiazinan-5-yl)benzenethiol (IX).
Rf 0.5 (chloroform–benzene–ethyl acetate, 1:5:1). IR
spectrum, ν, cm–1: 3300, 2900, 2600, 1600, 1100, 720.
1H NMR spectrum, δ, ppm: 4.25 br.s (2H, 2-H),
4.93 br.s (4H, 4-H, 6-H), 6.66–7.49 m (4H, 8-H, 9-H,
11-H, 12-H). 13C NMR spectrum, δC, ppm: 33.23 t
(C2), 55.02 t (C4, C6), 114.70 d (C8, C12), 118.03 d (C9,
C11), 131.96 s (C10), 137.72 s (C7). Mass spectrum, m/z
(Irel, %): 197 (35) [M – S]+, 136 (100) [M –
CH3SCH2S]+, 109 (35) [M – SPh]+. Found, %:
C 46.80; H 4.65; N 5.95; S 41.91. C9H11NS3. Calculat-
ed, %: C 47.12; H 4.83; N 6.11; S 41.94. M 229.
N-Methyl-1,3,5-dithiazinane. Hydrogen sulfide
(prepared by treatment of 40 mmol of sodium sulfide
with hydrochloric acid) was bubbled through 60 mmol
of a 37% aqueous formaldehyde solution over a period
of ~30 min. A solution of 20 mmol of methylamine
hydrochloride in water was then added dropwise, the
mixture was stirred for 3 h at 80°C, neutralized to pH 7
with a dilute solution of sodium hydroxide, and ex-
tracted with chloroform, and the extract was evaporat-
Cyclothiomethylation of arylamines with
1,3,5-trithiane (general procedure). A Schlenk flask
1
ed. Yield 40%. H NMR spectrum, δ, ppm: 2.54 br.s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

RAKHIMOVA et al.
1304
Gafiatullin, R.R., Russian Patent no. 2160233, 2000;
Byull. Izobret., 2000, no. 34.
equipped with a magnetic stirrer was charged under
argon with 11 mmol of 1,3,5-trithiane, 0.5 mmol of
FeCl3 ·6H2O as catalyst, and 10 mmol of the corre-
sponding arylamine in 5 ml of acetonitrile. The mix-
ture was stirred for 6 h at 60°C, and the products
(compounds I and V–IX) were purified by column
chromatography and identified by comparing with
authentic samples [9, 13, 14].
5. Kubota, K., Nakamoto, A., Moriguchi, M., Koba-
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This study was performed under financial support
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nos. 11-03-00101-a, 11-03-97011-r_Povolzh’e_a).
9. Nadyrgulova, G.R., Cand Sci. (Chem.) Dissertation,
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