Thiomethylation of heteroaromatic amines

Article abstract of DOI:10.1134/S1070428011060157

Thiomethylation of heteroaromatic amines with formaldehyde-hydrogen sulfide gave linear and cyclic heteroatom compounds: N,N′- [methylenebis(sulfanediylmethylene)]bishetarenamines and 5-hetaryl-1,3,5- dithiazinanes. N,N′-[Methylenebis(sulfanediylmethylene

Full text of DOI:10.1134/S1070428011060157

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 6, pp. 920–927. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.R. Akhmetova, Z.T. Niatshina, Z.A. Starikova, L.F. Korzhova, A.G. Ibragimov, 2011, published in Zhurnal Organicheskoi Khimii,
2011, Vol. 47, No. 6, pp. 903–910.
Thiomethylation of Heteroaromatic Amines
V. R. Akhmetovaa, Z. T. Niatshinaa, Z. A. Starikovab, L. F. Korzhovac, and A. G. Ibragimova
a Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
b Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
c Bashkir Republican Research Ecological Center, pr. Oktyabrya 147, Ufa, 450075 Bashkortostan, Russia
Received August 1, 2010
Abstract—Thiomethylation of heteroaromatic amines with formaldehyde–hydrogen sulfide gave linear and
cyclic heteroatom compounds: N,N′-[methylenebis(sulfanediylmethylene)]bishetarenamines and 5-hetaryl-
1,3,5-dithiazinanes. N,N′-[Methylenebis(sulfanediylmethylene)]bishetarenamines were found to undergo trans-
formation into 5-hetaryl-1,3,5-dithiazinanes by the action of CH2O–H2S. Transamination of 5-methyl-1H-
pyrazol-3-amine, 6-nitro-1,3-benzothiazol-2-amine, and 5-bromopyridin-2-amine with 5-methyl-1,3,5-dithia-
zinane selectively afforded the corresponding 5-hetaryl-1,3,5-dithiazinanes.
DOI: 10.1134/S1070428011060157
One-pot thiomethylation of amines with the CH2O–
H2S system [1] provides a simple and efficient syn-
thetic route to 1,3,5-thiadiazinanes and 1,3,5-dithia-
zinanes [2–5], some of which were found to exhibit
bactericidal, herbicidal, fungicidal, insecticidal, acari-
cidal, and antimicrobial activity [6–8].
biological activity (fungicidal, antimicrobial, anti-
tumor, and antioxidant) [11, 12].
In the present work we examined both synthetic
approaches to 1,3,5-thiadiazinanes and 1,3,5-dithiazin-
anes via thiomethylation of 5-methylisoxazol-3-amine
(Ia), 5-methyl-1H-pyrazol-3-amine (Ib), 4-methyl-,
5-methyl-, 4-phenyl- and 5-nitrothiazol-2-amines Ic–
If, 6-nitro-1,3-benzothiazol-2-amine (Ig), pyridine-2-
amine (Ih), pyridine-3-amine (Ii), pyridine-4-amine
(Ij), 4-methylpyridin-2-amine (Ik), and 5-bromopyr-
idin-2-amine (Il). We previously showed that substi-
tuted anilines undergo thiomethylation with CH2O–
H2S and that the reaction direction depends on both the
conditions and structural specificity of the substrate
1,3,5-Dithiazinanes can also be obtained by trans-
amination with N-tert-butyl-1,3,5-dithiazinane [9] or
by reaction of hydrogen sulfide with 1,3,5-trimethyl-
1,3,5-triazinane formed by condensation of methyl-
amine with formaldehyde [10]. There are no published
data on the synthesis of 1,3,5-dithiazinanes and
1,3,5-thiadiazinanes by thiomethylation of heteroaro-
matic amines, many of which possess various kinds of
Scheme 1.
Me
S
60°C
0°C
N
NH2
O
N
S
IIa
CH2O–H2S, EtOH
N
Me
O
S
Ia
H
H
N
N
N
N
+
Me
Me
Me
Me
N
N
N
N
O
O
O
O
IIIa, 70%
IVa, 3%
920

THIOMETHYLATION OF HETEROAROMATIC AMINES
921
Scheme 2.
Me
S
60°C
N
NH2
HN
N
S
IIb
CH2O–H2S, EtOH
N
Me
N
H
H
H
N
S
S
N
Ib
0°C
Me
Me
+
IIb
N
N
HN
NH
IVb
S
CH2O–H2S, EtOH
N
N
Ib
Me
Me
N
N
HN
NH
The structure of compounds IIa, IIb, IIIa, and IVb
[13]. As a result, either the corresponding 1,3,5-dithia-
zinanes or 1,3,5-thiadiazinanes are formed as the major
product. We recently reported on selective synthesis of
thermodynamically more stable 1,3,5-dithiazinanes by
thiomethylation of anilines with CH2O–H2S at 40–
60°C, the substrate–CH2O–H2S ratio being 1 :3 :2.
With a view to obtain thermodynamically less stable
1,3,5-thiadiazinanes the reaction was carried out at 0°C
at a substrate–CH2O–H2S ratio of 2:3:2 [9].
was confirmed by spectral data, and the structure of
bis-pyrazole IVb was unambiguously determined by
X-ray analysis (Fig. 1). Compounds IIa and IIb char-
acteristically showed in the 13C NMR spectrum signals
from carbon atoms in the heterorings at δC 94.4, 163.5,
and 169.6 (IIa) and 98.1, 138.9, and 152.2 ppm (IIb);
also, signals from methylene carbon atoms between
two sulfur atoms (δC 32.6–33.0 ppm) and between
nitrogen and sulfur atoms were present (δ 52.3–
56.2 ppm). The 1H NMR spectra of 1,3,5-dithiazinanes
IIa and IIb contained signals from methylene protons
at δ 3.59–3.92 (SCH2S) and 3.98–4.87 ppm (SCH2N)
at a ratio of 1:2. In the 13C NMR spectrum of IIIa,
methylene carbon atoms resonated at δC 50.2 (SCH2N)
and 64.2 ppm (NCH2N). The corresponding methylene
proton signals were observed in the 1H NMR spectrum
of IIIa at δ 4.39 (broadened singlet, SCH2N) and
4.87 ppm (NCH2N); their intensity ratio was 2:1. The
13C NMR spectrum of IVb contained signals belong-
ing to carbon nuclei in the pyrazole ring (δC 90.6,
140.7, 152.2 ppm) and methylene groups between
nitrogen and sulfur atoms (δC 46.3 ppm) and between
two sulfur atoms (δC 33.0 ppm). The NCH2S and
Thiomethylation of hetarylamines Ia–Il was per-
formed under analogous conditions, but only 5-methyl-
isoxazol-3-amine (Ia) behaved similarly to anilines.
The reaction of Ia with CH2O–H2S (reactant ratio
1:3:2) in ethanol at 60°C afforded the corresponding
1,3,5-dithiazinane IIa in 75% yield, whereas at 0°C,
the ratio Ia–CH2O–H2S being 2:3:2, we obtained 70%
of 1,3,5-thiadiazinane IIIa (Scheme 1). Unlike anilines,
thiomethylation of aminoisoxazole Ia was accom-
panied by formation of a small amount (3%) of linear
condensation product IVa in which two aminooxazole
fragments are linked by methylene bridge at the amino
groups (Scheme 1).
Like the reaction with aminoisoxazole Ia, thio-
methylation of 5-methyl-1H-pyrazol-3-amine (Ib) with
CH2O–H2S (reactant ratio 1:3:2) at 60°C gave pyra-
zolyl-substituted 1,3,5-dithiazinane IIb in 60% yield.
Analogous reaction at 0°C with 2 equiv of Ib, 3 equiv
of CH2O, and 2 equiv of H2S led to the formation of
a mixture of 1,3,5-dithiazinane IIb and N,N′-[meth-
ylenebis(sulfanediylmethylene)]bis(5-methyl-1H-pyra-
zol-3-amine) (IVb) at a ratio of 1:2 in an overall yield
of ~70% (Scheme 2). We failed to obtain the corre-
sponding 1,3,5-thiadiazinane from aminopyrazole Ib.
Compounds IIb and IVb were isolated by fractional
crystallization from aqueous ethanol.
H2N
N2
C2
C3
C4
C1
C1A
O1
N1
Fig. 1. Structure of the molecule of N,N′-methylenebis-
(5-methylisoxazol-3-amine) (IVa) according to the X-ray
diffraction data. Non-hydrogen atoms are shown as thermal
vibration ellipsoids with a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

AKHMETOVA et al.
922
Scheme 3.
S
S
N
60°C
0°C
R
+
IVc–IVe
N
NH2
S
S
IIc, IId
CH2O–H2S
N
R
H
H
N
CH2O–H2S (3:2)
CHCl3, 20°C
Ic–If
N
S
S
S
S
IIc, IId
N
N
R
R
S
IVc–IVe
R = 4-Me (c), 5-Me (d), 4-Ph (e), 5-O2N (f).
H
H
N
S
S
N
S
O2N
S
N
CH2O–H2S (3:2), 0–60°C
NH2
N
N
O2N
NO2
Ig
IVg, 5–10%
1
SCH2S signals in the H NMR spectrum of IVb were
located at δ 3.93 and 3.47 ppm, respectively, with
an intensity ratio of 2:1.
methylene)]bis(thiazol-2-amines) IVc and IVd can be
converted into the corresponding 1,3,5-dithiazinanes
IIc and IId in 50–60% yield by the action of CH2O–
H2S (Scheme 3).
Unlike pyrazole Ib, thiomethylation of 4- and
5-methylthiazol-2-amines Ic and Id at 0°C was selec-
tive, and substituted N,N′-[methylenebis(sulfanediyl-
methylene)]bis(thiazol-2-amines) IVc and IVd were
obtained in 68 and 63% yield, respectively (Scheme 3).
Raising the reaction temperature to 60°C led to the
formation of mixtures of 1,3,5-dithiazinanes IIc, IId
and IVc, IVd at a ratio of 2:1. Aminothiazoles Ie and
Ig turned out to be less reactive under classical thio-
methylation conditions. For example, aminothiazoles
Ie and Ig reacted with CH2O and H2S at 60°C (reactant
ratio 1:3:2) to produce 1,3,5-dithiazinanes IVe and
IVg, respectively, in 10–15% yield. The conversion of
Ie and Ig decreased to 5–8% upon lowering the
temperature. 5-Nitrothiazol-2-amine (If) failed to react
with CH2O and H2S in the temperature range from 0 to
60°C. In contrast to 4- and 5-methylthiazol-2-amines
Ic and Id, no corresponding 1,3,5-dithiazinanes were
formed in the reactions of 4-phenylthiazol-2-amine
(Ie) and 6-nitro-1,3-benzothiazol-2-amine (Ig) with
CH2O–H2S at 60°C. N,N′-[Methylenebis(sulfanediyl-
The H and 13C NMR spectra of IIc and IId con-
1
tained signals typical of 1,3,5-dithiazinane ring. The
structure of IVc–IVe and IVg was determined on the
basis of their spectral parameters. Compound IVc
showed in the IR spectrum absorption bands due to
stretching and bending vibrations of the NH groups at
3200 (broadened band) and 1570 cm–1, respectively.
Heteronuclear NMR correlation techniques revealed
couplings between the C2 atom in the thiazole ring and
methylene protons in the adjacent NCH2S fragment;
the carbon atom in the latter displayed in turn a cross
peak with protons in the SCH2S methylene group
(Fig. 2). Also, some other long-range heteronuclear
couplings were observed in the HMBC and COSY
spectra, which confirmed the assumed structure of
compound IVc (Fig. 2). The mass spectrum of IVc
(LC–MS) contained the molecular ion peak with
m/z 333 ([M + H]+), fragment ion peaks with m/z 299
[M – HS]+ and 207 [M – CH3 – C3H2NS – NC]+, and
ion peaks with m/z 147 and 127, which correspond to
elimination of the SCH2SCH2NHC3HNSCH3 and
CSCH2NHC3HNS(CH3)2 fragments from the molec-
ular ion.
H
N6
H12
S8
S10
N
S1
7
S14
2
9
13
15
H
H
11
5
N3
17N
H
H H
H
16
The direction of thiomethylation of 2-, 3-, and
4-aminopyridines Ih–Ij with CH2O–H2S depended on
their structure. Compounds Ih and Ii reacted like thia-
zoles to give linear oligomers IVh and IVi in ~25%
yield. Here, the most reactive was meta isomer Ii
which is characterized by the lowest basicity (kb =
4
18
Me19
H
H
Fig. 2. Heteronuclear 13C–1H couplings (HMBC) in the mol-
ecule of N,N′-[methylenebis(sulfanediylmethylene)]bis-
(4-methyl-1,3-thiazol-2-amine) (IVc).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

THIOMETHYLATION OF HETEROAROMATIC AMINES
923
Scheme 4.
H
H
CH2O–H2S (3:2)
EtOH, 0–60°C
N
N
S
S
N
N
N
NH2
R
R
R
Ih–Ik
IVh, IVi, IVk
R = H: 2-NH2 (h), 3-NH2 (i), 4-NH2 (j); R = 4-Me: 2-NH2 (k).
CH2O–H2S (3:2)
EtOH, 0–60°C
Br
Br
Br
S
S
+
Br
N
N
N
NH2
N
N
S
S
N
N
H
H
Il
IVl
IIl
CH2O–H2S (3 :2)
IVl
IIl
9.6×10–9 [14]); the yield of N,N′-[methylenebis(sul-
fanediylmethylene)]bis(pyridin-3-amine) (IVi) was
25%. ortho Isomer Ih (kb = 7.2× 10–8 [13]) gave rise to
20% of linear oligomer IVh, whereas thiomethylation
of para isomer Ij (kb 1.5×10–5 [13]) failed to occur.
The presence of a methyl group in the pyridine ring
does not affect the reactivity of 2-aminopyridine to
an appreciable extent. Thiomethylation of Ik gave
compound IVk in ~24% yield, whereas 5-bromo-
pyridin-2-amine (Il) readily reacted with formaldehyde
and hydrogen sulfide at 0°C to produce a mixture of
1,3,5-dithiazinane IIl and N,N′-[methylenebis(sul-
fanediylmethylene)]bis(5-bromopyridin-2-amine)
(IVl) in 24 and 38% yield, respectively. Raising the
temperature to 60°C did not change the reaction direc-
tion, but the yield of the corresponding N,N′-[meth-
ylenebis(sulfanediylmethylene)]bishetarenamines IVh,
IVi, and IVk and 1,3,5-di-thiazinane IIl increased
(Scheme 4). Like compounds IVc and IVd, bis-amino-
pyridine IVl fairly readily reacted with CH2O–H2S,
yielding 51% of 1,3,5-dithiazinane IIl.
δC 51.9 ppm (NCH2S) and 32.9 ppm (SCH2S). The
corresponding methylene protons resonated in the
1H NMR spectrum at δ 5.10 (NCH2S) and δ 4.26 ppm
(SCH2S). In the 13C NMR spectra of IVh, IVi, IVk,
and IVl signals from methylene carbon atoms in the
NCH2S and SCH2S fragments were located at δC 43.0–
44.8 and 32.7–33.0 ppm, respectively; the NCH2S and
SCH2S protons gave rise to signals at δ 4.60-4.68 and
3.85–4.16 ppm, respectively.
Thus, reactions of heteroaromatic amines Ib–Il
with CH2O–H2S give mainly products of intermolec-
ular thiomethylation at the NH2 groups. Presumably,
this reaction direction is favored by the ability of het-
arylamines to form associates in solution [15], as well
as to undergo fast prototropic amine–imine tauto-
merism [16].
Insofar as we failed to obtain N-hetaryl-1,3,5-di-
thiazinanes in high yield, we also tried to synthesize
the same compounds via reaction of hetarylamines Ia–
Il with 5-methyl-1,3,5-dithiazinane (V) which may be
regarded as synthetic equivalent of the thiomethylating
agent (CH2O–H2S, 3:2). The reaction of N-methyldi-
thiazinane V with compounds Ia–Il was performed
under conditions of thermal and catalytic transamina-
tion. In the first case, equimolar amounts of the reac-
The 13C NMR spectrum of compound IIl contained
signals from carbon atoms in the pyridine ring at
δC 108.2, 110.0, 138.6, 146.4, and 157.3 ppm and
methylene carbon atoms in the dithiazinane ring at
Scheme 5.
S
S
SmCl3 ·6H2O, CHCl3
RNH2
+
+
MeNH2
N
S
N
S
Me
R
Ib, Ig, Il
V
IIb, IIg, IIl
Br
N
S
R =
(b),
(g),
(l).
N
Me
N
O2N
N
H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

AKHMETOVA et al.
924
tants (compounds I and V) were heated in boiling
chloroform, whereas the catalytic reaction was carried
out at 20°C in the presence of 5 mol % of NiCl2·6H2O,
FeCl3·6H2O, SmCl3 ·6H2O, or Sm(NO3)3·6H2O over
a period of 3 h. Among the examined catalysts, the
most effective was SmCl3 ·6 H2O. Catalysts on the
basis of samarium, iron, and nickel salts and com-
plexes were selected taking into account their high
catalytic activity in the condensation of aniline with
aldehydes [17, 18] and in the aminomethylation of CH
acids with geminal diamines [19].
250°C. LC–MS data for compounds IIIa and IVc were
obtained on a Shimadzu LCMS-2010 EV instrument
(atmospheric pressure chemical ionization, ion source
temperature 500°C, vaporizer temperature 250°C, car-
rier gas N2, flow rate 2.5 ml/min, liquid phase flow
rate 0.05 ml/min, positive ion source voltage 4.5 kV).
X-Ray diffraction data for compound IVa. Color-
less plates, monoclinic crystal system, space group
C2/c. Unit cell parameters (120 K): a = 9.6944(7), b =
11.3029(9), c = 9.8277(7) Å; β = 111.733(1)°, V =
1000.3(1) Å3; Z = 4; dcalc = 1.376 g/cm3. Reflection
intensities were measured on a Bruker SMART 1000
CCD diffractometer [λ(MoKα) 0.71073 Å, ω-scanning,
2θ = 60°]. Number of independent reflections 1453
(Rint = 0.0204). The structure was solved by the direct
method and was refined by the full-matrix least-
squares procedure with respect to F2 in anisotropic ap-
proximation (for non-hydrogen atoms). The position of
the H2N hydrogen atom was determined by the Fourier
difference synthesis, and hydrogen atoms attached to
carbons were placed into positions calculated on the
basis of geometry considerations. The positions of all
hydrogen atoms were refined in isotropic approxima-
tion. The final divergence factors were R1 = 0.0416 for
1249 reflections with I > 2σ(I) and wR2 = 0.0964 for
all independent reflections; goodness of fit 1.007,
F(000) = 436, 74 refined parameters. All calculations
were performed on an IBM PC/AT using SHELXL
software package [20]. The complete set of crystallo-
graphic data for compound IVa (coordinates of atoms,
bond lengths, bond angles, and thermal parameters)
was deposited to the Cambridge Crystallographic Data
Centre (entry no. CCDC 784385) and is available at
www.ccdc.cam.uk/conts/retrieving.html (CCDC,
12 Union Road, Cambridge CB2 1EZ; fax:
+441223335033; deposit@ccdc.cam.ac.uk).
In our experiments the conversion of heteroaro-
matic amines Ia–Il in the thermal reaction (CHCl3,
60°C, 24 h) was 10–80%, while the catalytic reaction
(20°C, 3 h) was characterized by a conversion higher
than 70%. Under the conditions of thermal transamina-
tion, only compounds Ia–Id and Il were selectively
converted into the corresponding dithiazinanes IIa–IId
and IIl in 10–20% yield, whereas the reactions with
hetarylamines Ie–Ik were accompanied by formation
of intermolecular thiomethylation products. Likewise,
mixtures containing dithiazinanes, thiadiazinane, and
linear N,N′-[methylenebis(sulfanediylmethylene)]bis-
(hetarenamines) were formed in the catalytic trans-
amination of compounds I, except for amines Ib, Ig,
and Il. 5-Methyl-1H-pyrazol-3-amine (Ib), 6-nitro-1,3-
benzothiazol-2-amine (Ig), and 5-bromopyridin-2-
amine (Il) reacted with compound V in chloroform in
the presence of 5 mol % of SmCl3·6H2O (20°C, 3 h)
to afford the corresponding N-hetaryl-1,3,5-dithia-
zinanes IIb, IIg, and IIl in ~70% yield (Scheme 5).
EXPERIMENTAL
The 1H and 13C NMR spectra were recorded on Jeol
1
FX 90Q (89.55 MHz for H and 22.50 MHz for 13C)
1
and Bruker AM-400 spectrometers (400 MHz for H)
Thiomethylation of heteroaromatic amines (gen-
eral procedure). A 37% solution of formaldehyde,
27 or 13.5 mmol, was saturated with hydrogen sulfide
(prepared from hydrochloric acid and sodium sulfide)
over a period of 20 min, 9 mmol of amine Ia–Il was
added, and the mixture was stirred for 10–12 h at 0 or
60°C. The precipitate (compound IIa, IIIa, IVc–IVe,
IVg, IVh, or IVk) was filtered off and washed with
ethanol; compounds IIb, IVa, and IVb were isolated
by fractional crystallization; and compounds IIl and
IVl were isolated by column chromatography using
benzene–ethyl acetate (9:1) as eluent.
using tetramethylsilane as internal reference. Homo-
and heteronuclear HMBC and HSQC experiments
were performed following standard Bruker procedures.
The IR spectra were measured on a Specord 75IR
spectrometer (Carl Zeiss, Jena) from samples dispersed
in mineral oil. The elemental compositions were deter-
mined on a Carlo Erba 1106 analyzer. The melting
points were determined using an PHMK 80/2617
melting point apparatus. Gas chromatographic–mass
spectrometric analysis of compounds IIa and IIl was
performed on a Finnigan 4021 GC–MS system
equipped with a glass capillary column, 50 000×
0.25 mm, stationary phase HP-5, carrier gas helium,
injector temperature 280°C, ion source temperature
5-(5-Methylisoxazol-3-yl)-1,3,5-dithiazinane
(IIa). Yield 75%, mp 146–148°C. 1H NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

THIOMETHYLATION OF HETEROAROMATIC AMINES
925
(DMSO-d6), δ, ppm: 2.32 s (3H, CH3), 3.92 br.s (2H,
2-H), 4.87 br.s (4H, 4-H, 6-H), 6.20 s (1H, 4′-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 12.1 q (CH3),
32.6 (C2), 52.3 (C4, C6), 94.4 (C4′), 163.5 (C3′), 169.6
(C5′). Mass spectrum, m/z (Irel, %): 202 (45) [M]+, 124
(24), 111 (100), 68 (15), 46 (16), 42 (30). Found, %:
C 40.64; H 4.71; N 13.48; S 32.19. C7H10N2OS2. Cal-
culated, %: C 41.56; H 4.98; N 13.85; S 31.70.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(5-methyl-1,3-thiazol-2-amine) (IVd). Yield 63%,
mp 169–170°C. H NMR spectrum (DMSO-d6), δ,
ppm: 2.22 s (6H, CH3), 3.92 s (2H, 3′-H), 4.52 s (4H,
1′-H, 5′-H), 6.76 s (2H, 4-H), 8.09 br.s (2H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 11.4 (CH3),
24.5 (C3′), 45.5 (C1′, C5′), 121.0 (C5), 135.5 (C4), 166.2
(C2). Found, %: C 38.95; H 4.74; N 16.57; S 37.96.
C11H16N4S4. Calculated, %: C 39.73; H 4.85; N 16.85;
S 38.57.
1
5-(5-Methyl-1H-pyrazol-3-yl)-1,3,5-dithiazinane
1
(IIb). Yield 60%, tarry yellow substance. H NMR
spectrum (DMSO-d6), δ, ppm: 2.08 s (CH3), 3.59 (2H,
2-H), 3.98 (4H, 4-H, 6-H), 5.20 s (1H, 4′-H), 5.61 s
(NH). 13C NMR spectrum (DMSO-d6), δC, ppm: 18.5 q
(CH3), 32.9 (C2), 56.2 (C4, C6), 98.1 (C4′), 138.9 (C3′),
152.2 (C5′). Found, %: C 41.11; H 5.26; N 20.00;
S 32.13. C7H11N3S2. Calculated, %: C 41.76; H 5.51;
N 20.87; S 31.86.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(4-phenyl-1,3-thiazol-2-amine) (IVe). Yield 18%,
mp 103–105°C. H NMR spectrum (DMSO-d6), δ,
ppm: 4.09 s (2H, 3′-H), 4.34 s (4H, 1′-H, 5′-H), 7.28–
7.80 m (10H, Ph), 8.34 s (2H, 5-H), 9.24 s (2H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 37.9 (C3′),
46.9 (C1′, C5′), 128.2 (Carom), 128.9 (C5), 130.0 (Carom),
135.5 (Carom), 168.5 (C4), 171.0 (C2). Found, %:
C 55.12; H 4.46; N 12.56; S 28.89. C21H20N4S4. Cal-
culated, %: C 55.23; H 4.41; N 12.27; S 28.09.
1
3,5-Bis(5-methylisoxazol-3-yl)-1,3,5-thiadiazinane
1
(IIIa). Yield 70%, mp 198–200°C. H NMR spectrum
(DMSO-d6), δ, ppm: 2.25 s (6H, CH3), 4.13 br.s (4H,
2-H, 6-H), 4.87 br.s (2H, 4-H), 6.20 s (2H, 3′-H),
5.61 s (NH). 13C NMR spectrum (DMSO-d6), δC, ppm:
12.0 (CH3), 50.2 (C2, C6), 64.2 (C4), 94.3 (C4′), 163.9
(C3′), 168.9 (C5′). Mass spectrum, m/z (Irel, %): 267
(100) [M + H]+, 227 (30), 203 (30), 143 (18), 99 (71),
65 (3). Found, %: C 50.07; H 4.99; N 21.56; S 12.78.
C11H14N4O2S. Calculated, %: C 49.61; H 5.30;
N 21.04; S 12.04.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(6-nitro-1,3-benzothiazol-2-amine) (IVg). Yield 10%,
1
mp 154–156°C. H NMR spectrum (DMSO-d6), δ,
ppm: 4.00 s (2H, 3′-H), 4.75 br.s (4H, 1′-H, 5′-H),
7.57 d (2H, 2H, Harom, J = 8.8 Hz), 8.15 d (2H, 2H,
H
arom, J = 8.8 Hz), 8.72 br.s (2H, Harom), 9.42 s (2H,
NH). 13C NMR spectrum (DMSO-d6), δC, ppm: 33.3
(C3′), 45.8 (C1′, C5′), 117.9 (Carom), 118.3 (Carom), 122.4
(Carom), 132.1 (Carom), 141.3 (Carom), 158.0 (Carom),
170.7 (C2). Found, %: C 41.07; H 2.99; N 16.56;
S 25.78. C17H14N6O4S4. Calculated, %: C 41.28;
H 2.85; N 16.99; S 25.93.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(5-methyl-1H-pyrazol-3-amine) (IVb). Yield 45%,
1
mp 198–200°C. H NMR spectrum (DMSO-d6), δ,
ppm: 2.08 s (6H, CH3), 3.47 br.s (2H, 3′-H), 3.93 br.s
(4H, 1′-H, 5′-H), 5.22 s (2H, 4-H), 6.00 br.s (NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 11.4 (CH3),
33.0 (C3′), 46.4 (C1′, C5′), 90.6 (C4), 140.73 (C3),
152.2 s (C5). Found, %: C 44.77; H 6.12; N 28.56;
S 22.08. C11H18N6S2. Calculated, %: C 44.27; H 6.08;
N 28.16; S 21.49.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(pyridin-2-amine) (IVh). Yield 24%, mp 162–164°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 3.94 s (2H,
3′-H), 4.68 s (4H, 1′-H, 5′-H), 5.83 s (2H, NH), 6.39 d
(2H, 3-H, J = 6.0 Hz), 6.62 d (2H, 5-H, J = 6.4 Hz),
7.02 d (2H, 4-H, J = 6.0 Hz), 7.45 d (2H, 6-H, J =
6.3 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
32.8 (C3′), 43.0 (C1′, C5′), 108.0 (C3), 111.9 (C5), 137.0
(C4), 147.6 (C6), 157.3 (C2). Found, %: C 52.96;
H 5.70; N 19.25; S 22.01. C13H16N4S4. Calculated, %:
C 53.43; H 5.47; N 19.18; S 21.92.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(4-methyl-1,3-thiazol-2-amine) (IVc). Yield 68%,
mp 138–140°C. IR spectrum (KBr), ν, cm–1: 3200,
1570, 1595, 1445, 1300, 1140, 1090, 950–900, 695–
1
645. H NMR spectrum (DMSO-d6), δ, ppm: 2.06 s
(6H, CH3), 3.87 s (2H, 3′-H), 4.45 s (4H, 1′-H, 5′-H),
6.25 s (2H, 5-H), 8.02 br.s (2H, NH). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 17.5 (CH3), 34.0 (C3′), 46.2
(C1′, C5′), 101.8 (C5), 148.3 (C4), 167.8 (C2). Mass
spectrum, m/z (Irel, %): 333 (100) [M + H]+, 299 (30),
207 (30), 178 (32), 147 (35), 127 (50). Found, %:
C 40.05; H 4.50; N 16.02; S 39.21. C11H16N4S4. Cal-
culated, %: C 39.73; H 4.85; N 16.85; S 38.57.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(pyridin-3-amine) (IVi). Yield 28%, mp 110–112°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 3.98 s (2H,
3′-H), 4.60 s (4H, 1′-H, 5′-H), 6.99 d (2H, 4-H, J =
6.4 Hz), 7.09 s (2H, 2-H), 7.72 d (2H, 5-H, J =
6.3 Hz), 7.96 d (2H, 6-H, J = 6.0 Hz), 8.09 s (2H, NH).
13C NMR spectrum (DMSO-d6), δC, ppm: 33.0 (C3′),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

AKHMETOVA et al.
926
44.8 (C1′, C5′), 119.3 (C5), 123.4 (C4), 136.5 (C2), 142.3
(C3), 144.8 (C6). Found, %: C 54.00; H 5.74; N 19.45;
S 22.00. C13H16N4S2. Calculated, %: C 53.43; H 5.47;
N 19.18; S 21.92.
5-(4-Methyl-1,3-thiazol-2-yl)-1,3,5-dithiazinane
(IIc). Yield 60%, tarry substance. 1H NMR spectrum
(DMSO-d6), δ, ppm: 2.53 s (3H, CH3), 3.67 s (2H,
2-H), 4.21 s (4H, 4-H, 6-H), 6.92 s (1H, 5′-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 17.6 (CH3),
33.2 (C2), 56.4 (C4, C6), 113.5 (C4′), 138.1 (C5′), 163.1
(C2′). Found, %: C 39.05; H 4.35; N 12.80; S 45.21.
C7H10N2S3. Calculated, %: C 38.50; H 4.62; N 12.83;
S 44.05.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(4-methylpyridin-2-amine) (IVj). Yield 27%,
1
mp 138–140°C. H NMR spectrum (DMSO-d6), δ,
ppm: 2.08 s (6H, CH3), 4.16 s (2H, 3′-H), 4.62 s (4H,
1′-H, 5′-H), 5.02 s (2H, NH), 6.45 s (4H, 3-H),
7.15 br.s (2H, 5-H), 7.86 br.s (2H, 6-H). 13C NMR
spectrum (DMSO-d6), δC, ppm: 16.8 (CH3), 32.7 (C3′),
43.4 (C1′, C5′), 107.8 (C3), 121.2 (C5), 138.0 (C6), 146.7
(C4), 155.4 (C2). Found, %: C 56.17; H 6.31; N 17.52;
S 20.15. C15H20N4S2. Calculated, %: C 56.22; H 6.29;
N 17.48; S 20.01.
5-(5-Methyl-1,3-thiazol-2-yl)-1,3,5-dithiazinane
1
(IId). Yield 50%, tarry substance. H NMR spectrum
(DMSO-d6), δ, ppm: 2.35 s (3H, CH3), 4.31 s (2H,
2-H), 5.07 s (4H, 4-H, 6-H), 7.02 s (1H, 5′-H).
13C NMR spectrum (DMSO-d6), δC, ppm: 12.0 (CH3),
31.7 (C2), 52.4 (C4, C6), 111.8 (C4′), 128.3 (C5′), 167.8
(C2′). Found, %: C 38.78; H 4.70; N 12.11; S 43.81.
C7H10N2S3. Calculated, %: C 38.50; H 4.62; N 12.83;
S 44.05.
N,N′-[Methylenebis(sulfanediylmethylene)]bis-
(5-bromopyridin-2-amine) (IVl). Yield 50%, tarry
1
yellow substance. H NMR spectrum (DMSO-d6), δ,
Compound IIl. Yield 50%. Mass spectrum, m/z
(Irel, %): 276 (55) [M]+, 243 (52), 199 (75), 185 (82),
157 (100), 78 (70), 45 (29).
ppm: 3.85 s (2H, 3′-H), 4.61 s (4H, 1′-H, 5′-H), 6.44 d
(2H, 3-H, J = 7.6 Hz), 7.30 s (2H, 6-H), 7.52 d (2H,
4-H, J = 8.0 Hz), 8.16 s (2H, NH). 13C NMR spectrum
(DMSO-d6), δC, ppm: 32.90 (C3′), 44.1 (C1′, C5′), 109.2
(C3), 110.8 (C5), 139.6 (C4), 148.4 (C6), 155.4 (C2).
Found, %: C 34.55; H 3.16; Br 35.55; N 113.0;
S 15.01. C13H14Br2N4S2. Calculated, %: C 34.67;
H 3.11; Br 35.56; N 12.44; S 14.22.
Transamination of hetarenamines with N-meth-
yl-1,3,5-dithiazinane (general procedure). A mixture
of 0.7 mmol of 5-methyl-1,3,5-dithiazinane, 0.35 mmol
of the corresponding heteroaromatic amine, and
0.017 mmol of SmCl3·6H2O in chloroform was stirred
for 3 h at 20°C under argon. The mixture was passed
through a layer of silica gel and evaporated.
5-(5-Bromopyridin-2-yl)-1,3,5-dithiazinane (IIl).
1
Yield 36%, mp 117–118°C. H NMR spectrum
1
Compound IIb. Yield 70%. H NMR spectrum
(CDCl3), δ, ppm: 4.26 s (2H, 2-H), 5.10 s (4H, 4-H,
6-H), 6.74 d (1H, 3′-H, J = 8 Hz), 7.72 d (1H, 4′-H, J =
(DMSO-d6), δ, ppm: 2.10 s (3H, CH3), 3.52 d (2H,
2-H), 4.00 d (4H, 4-H, 6-H), 5.21 s (1H, 4′-H),
5.62 br.s (NH).
13
8 Hz), 8.60 s (1H, 6′-H). C NMR spectrum (CDCl3),
δC, ppm: 32.9 (C2), 51.9 (C4, C6), 108.2 (C5′), 110.0
(C3′), 138.6 (C4′), 146.4 (C6′), 157.3 (C2′). Mass spec-
trum, m/z (Irel, %): 276 (59) [M]+, 243 (54), 199 (78),
185 (86), 157 (100), 78 (75), 45 (35). Found, %:
C 34.85; H 3.35; Br 28.95; N 10.80; S 23.21.
C8H9BrN2S2. Calculated, %: C 34.66; H 3.27; Br 28.82;
N 10.11; S 23.14.
5-(6-Nitro-1,3-benzothiazol-2-yl)-1,3,5-dithiazin-
1
ane (IIg). Yield 69%, tarry substance. H NMR spec-
trum (DMSO-d6) δ, ppm: 3.91 s (2H, 2-H), 4.71 s (4H,
4-H, 6-H), 7.52 d (1H, 5′-H, J = 8 Hz), 8.11 d (1H,
4′-H, J = 8 Hz), 8.63 br.s (1H, 7′-H). 13C NMR spec-
trum (DMSO-d6), δC, ppm: 33.0 (C2), 56.1 (C4, C6),
116.8 (C5′), 117.7 (C8′), 121.9 (C7′), 131.4 (C4′), 140.8
(C6′), 157.6 (C9′), 171.8 (C2′). Found, %: C 39.98;
H 3.10; N 14.16; S 32.58. C10H9N3S3O2. Calculated,
%: C 40.13; H 3.01; N 14.05; S 32.11.
Reaction of N,N′-[methylenebis(sulfanediylmeth-
ylene)]bishetarenamines with CH2O and H2S (gen-
eral procedure). Hydrogen sulfide was bubbled over
a period of 30 min at 20–40°C through a 37% aqueous
solution of formaldehyde (1.8 mmol), 0.6 mmol of
N,N′-[methylenebis(sulfanediylmethylene)]bishetaren-
amine IVc, IVd, or IVl in 5 ml of 96% ethanol was
gradually added, and the mixture was stirred for ~10 h.
The precipitate (compound IIc or IId) was filtered off,
washed with ethanol, and dried; compound IIl was
extracted into chloroform, and the extract was
evaporated.
Compound IIl. Yield 70%. Mass spectrum, m/z
(Irel, %): 276 (55) [M]+, 243 (52), 199 (75), 185 (82),
157 (100), 78 (70), 45 (29).
The authors thank L.V. Spirikhin (Head of the
Laboratory of Physicochemical Analytical Methods,
Institute of Organic Chemistry, Ural Research Center,
Russian Academy of Sciences) and his co-workers for
performing LC–MS analyses. This study was per-
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THIOMETHYLATION OF HETEROAROMATIC AMINES
927
Korzhova, L.F., and Kunakova, R.V., Izv. Ross. Akad.
Nauk, Ser. Khim., 2010, p. 980.
10. Flores-Parra, A. and Sanches-Ruiz, S.A., Heterocycles,
formed under financial support by the Chemistry and
Materials Science Department, Russian Academy of
Sciences (program OKhNM-7).
1999, vol. 51, p. 2079.
11. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
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