Multicomponent heterocyclization of carboxamides with H2S and CH2O

Article abstract of DOI:10.1134/s1070428008020036

Multicomponent heterocyclization of aliphatic amides with H₂S and CH₂O (1:3:2) in water-organic solvent mixture in the presence of BuONa led to the formation of 1,3,5-dithiazinane in high yield (30-95%) and with high selectivity (100%). Under these conditions benzamide gave 3,5-dibenzoyl-1,3,5-thiadiazinane in 74% yield, whereas due to ortho-effect the acetylsalicylamide with H₂S and CH₂O in a system BuOH-H₂O without BuONa formed N-acetylsalicyloyl-1,3,5-dithiazinane (80%). Heterocyclization of α-aminosuccinic acid monoamide depending on the H₂S and CH₂O concentration occurred either at one or both NH₂ yielding respectively mono-or bisdithiazinanes.

Full text of DOI:10.1134/s1070428008020036

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 2, pp. 190−196. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V. R. Akhmetova, R.R. Khairullina, G.R. Nadyrgulova, R.V. Kunakova, U.M. Dzhemilev, 2008, published in Zhurnal
Organicheskoi Khimii, 2008, Vol. 44, No. 2, pp. 200−206.
Multicomponent Heterocyclization of Carboxamides
with H2S and CH2O
V. R. Akhmetovaa, R. R. Khairullinaa,b, G. R. Nadyrgulovaa,
R. V. Kunakovab, and U. M. Dzhemileva
aInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia
e-mail: ink@anrb.ru
bUfa State Academy of Economy and Service, Ufa, Russia
Received January 10, 2007
Abstract—Multicomponent heterocyclization of aliphatic amides with H2S and CH2O (1:3:2) in water-organic
solvent mixture in the presence of BuONa led to the formation of 1,3,5-dithiazinane in high yield (30–95%) and
with high selectivity (100%). Under these conditions benzamide gave 3,5-dibenzoyl-1,3,5-thiadiazinane in 74%
yield, whereas due to ortho-effect the acetylsalicylamide with H2S and CH2O in a system BuOH–H2O without
BuONa formed N-acetylsalicyloyl-1,3,5-dithiazinane (80%). Heterocyclization of α-aminosuccinic acid
monoamide depending on the H2S and CH2O concentration occurred either at one or both NH2 yielding respectively
mono- or bisdithiazinanes.
DOI: 10.1134/S1070428008020036
Nowadays the interest still exist to synthetic
heterocycles containing sulfur and nitrogen applicable
as catalysts in the phase transfer processes, efficient
extractants, sorbents, flotation reagents, and also as
antibacterial, anticancer, and antiHIV agents [1, 2].
of temperature, the sequence of the reagents and catalyst
addition to the reaction mixture. Mineral acids and bases
were applied as catalysts.
It was established that acetamide (Ib) brought into
the reaction under the chosen conditions and at the
reagents ratio acetamide (Ib)–CH2O–H2S 1:3:2 was not
involved into the cyclothiomethylation. However on
adding to the reaction mixture BuONa in amount 2 mol
per mol of the initial amide the lability of hydrogen atoms
in the initial amide notably grew and therefore it was
involved into the cyclocondensation with H2S and CH2O
giving the corresponding 1,3,5-dithiazinane IIb in
a sufficiently good yield.
One of promising methods of preparation of N,S-
containing heterocycles, namely, 1,3,5-dithiazinanes and
1,3-thiazetidines is the cyclothiomethylation of primary
amines with H2S and CH2O [3–10]. Until our studies
carboxamides were not involved into the cyclo-
condensation with H2S and CH2O.
Taking into consideration the practical significance
of dithiazinanes, thiadiazinanes, and their derivatives as
selective sorbents and also aiming at the development of
preparation methods for these classes compounds we
studied the multicomponent condensation of aliphatic
and aromatic carboxamides with H2S and CH2O.
In the presence of other bases (Et3N, NaOH, K2CO3,
NaOH/BuOH, NaOH/EtOH, and EtONa/EtOH)
independent of the temperature (0–80°C) the reaction of
amide Ib with H2S and CH2O resulted in trithiolane IX
[8]. Similar results were also obtained at acidifying the
reaction mixture (Ib–CH2O–H2S, 1:3:2) with HCl.
We selected for objects of investigation formamide,
acetamide, caproamide, 2-cyanoacetamide, trifluoroacet-
amide, acrylamide, benzamide, acetylsalicylamide, and
2-aminosuccinic acid monoamide (D-asparagine) (Ia–
Ii).
The basic properties of amino group in amides are
known to be considerably weakened due to the
replacement of a hydrogen by an acid residue [11]. As
a result strong mineral acids and bases form salts with
amides that decompose under the action of water giving
the initial amide and the corresponding acid. It was also
established [12] that potassium salts of heterylcyano-
To develop the optimum conditions of the synthesis
of N-acyl-1,3,5-dithiazinanes we studied by an example
of the cyclothiomethylation of acetamide (Ib) the effect
190

MULTICOMPONENT HETEROCYCLIZATION OF CARBOXAMIDES
191
amides were stable compounds and N-alkylheteryl-
cyanoamides were obtained therefrom.
Potentiometric analysis showed that under the
treatment of bases like NaOH, K2CO3, NaOH/BuOH,
and NaOH/EtOH acetamide (Ib) was hydrolyzed to
acetic acid (see the figure), whereas bases EtONa/EtOH
and BuONa/BuOH conserved the amide group, and the
activity of the alcoholates in the formation of molecular
complexes with amides depended on the positive charge
value on the sodium atom and on the structure of the
initial alcoholate growing in going from methylate
(sodium charge in the units of ionic character of the
chemical bond +1.335) to butylate (Na +2.385) [13, 14].
In this connection we chose as the optimum activating
system for amides a solution of sodium butylate in
butanol (pH 11.25). As optimum reaction temperature
was found to be 40°C. At higher temperature tarring
occurred, at lower temperature the target dithiazinanes
were obtained in lower yields (10−20%).
Variation of the medium pH depending on the reaction time
and catalytic system: NaOH + H2O (1), K2CO3 (2), NaOH +
BuOH (3), NaOH + EtOH (4), EtONa/EtOH (5), BuONa/
BuOH (6).
In order to elucidate the mechanism of activation by
BuONa in amides cyclocondensation with H2S and CH2O
we studied the interaction of acetamide with BuONa
dissolved in BuOH by means of IR and 1H and 13C NMR
spectroscopy. For instance in the 1H NMR spectrum of
acetamide (Ib) the characteristic signals of the methyl
group protons appeared at δ 2.21 ppm, and of amino
group protons, at δ 7.07–7.78 ppm. After adding the
reagent BuONa/BuOH in a ratio Ib–BuONa 1:2
(Scheme 1) the signals suffered an upfield shift, namely
the CH3 group to δ 1.78 ppm, NH2 group to δ 5.19–
5.55 ppm. In the 13C NMR spectrum thesignal of the
methyl group of acetamide shifted downfield, from δ
20.27 ppm for compound Ib to δ 20.59 ppm for the
complex (Ib)·[BuONa]2 (A), and the signal of the
carboxy group, upfield from δ 174.87 to 173.96 ppm. At
the same time we registered the proton and carbon signals
from the butyl group in BuONa molecule. Thus in the
1H NMR spectrum signals were observed at 0.69, 1.24,
and 3.35 ppm with the ratio of ontegral intensities 3:4:2,
and in the 13C NMR spectrum appeared signals at δ 12.45,
17.93, 33.85, and 60.35 ppm belonging to the methyla
and the methylene carbon atoms.
In the IR spectrum the absorption band of the carbonyl
group of amide Ib, ν 1660 cm–1, is conserved in complex
A, whereas the bending vibrations of the amino group of
amide Ib, ν 1630–1645 cm–1, in complex A shift to short-
wave region by 10–20 cm–1 with simultaneous decrease
in intensity. Monodentate ligands with the coordination
center on the nitrogen atom in complex with metals were
described [15].
Complex (Ib)·[BuONa]2 apparently is of A structure
where the chelating of ions Na occurs at the nitrogen.
As a result the lability of hydrogen atoms of the amide
group grows in reaction with thioacetals B formerly
found by GC-MS analysis as intermediates in the
thiomethylation of aliphatic amines with a mixture
CH2O–H2S [7]. Obviously in the coordinated amide
A the lability of protons originates rom the Coulomb
repulsion from the positively charged sodium ions [16].
Further cyclocondensation of N,N-bis(mercapto-
methyl)acetamide C with methylene glycol D resulted
in N-acetyl-1,3,5-dithiazinane (IIb) (Scheme 1).
Scheme 1.
OBu
Na
H
N
O
O
HO
O
O
2
OH
HS
OH
S
S
SH
SH
2BuONa
D
B
H3C
H3C
N
N
R
H
_2H2O
H3C
NH2
IIb
Na+
A
Ib
OBu
C
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AKHMETOVA et al.
192
Thus under the condition chosen by us for the
lone pair of the nitrogen with the π-electrons of the
aromatic ring or the double bond. Therefore the hetero-
cyclization of acrylamide (If) alongside the 1,3,5-di-
thiazinane IIf gave 1,3,5-thiadiazinane IIIf. In thio-
methylation of acrylamide (If) in the absence of BuONa
two and more molecules of compound If were involved
into the cyclocondensation leading to the formation of
heterocycle IVf. With growing reaction temperature
(40°C) the number of acrylamide units in compound IVf
increased and therefore the macroheterocycles IVf
obtained possessed lower solubility (Scheme 3).
heterocyclization of acid amides Ia–Ie with H2S and
CH2O the reaction of initial amides Ia–Ie in the presence
of BuONa with water solution of formaldehyde (37%)
saturated with the hydrogen sulfide proceeded at the
reagents ratio amide–H2S–CH2O 1:2:3 for 6 h at 40°C.
Aliphatic amides Ia–Ie provided exclusively 1,3,5-
dithiazinanes IIa–IIe in 30–95% yields (Scheme 2).
Scheme 2.
O
S1
6
O
The formation of compound IVf is indicated by the
presence in its 13C NMR spectrum of signals character-
istic of methylene groups located between nitrogen and
sulfur atoms, δ 39.79 and 40.84 ppm, and also of carbon
atoms of the double bond at δ 127.45 and 131.45 ppm
and of a carbonyl carbon at δ 166.23 ppm. In the 1H NMR
spectrum of compound IVf the hydrogen atoms of the
methylene group give rise to a multiplet in the region
4.65–4.75 ppm, and the signals of the hydrogens at the
double bond appear as a multiplet in the region 5.71–
6.24 ppm.
CH2O + H2S, 3:2
8
R
5
N
7
2
R
NH2
Ia_Ie
BuONa/BuOH,
40oC
S3
IIa_IIe
4
R = H (a), CH3 (b), CH2CH2CH2CH2CH3 (c), NCCH2
(d), CF3 (e).
We found that the yields of the target dithiazinanes
IIa–IIe grew in the series of amides having in the
hydrocarbon chain of the molecule the following groups:
n-C5H11<CH3<H<CNCH2<CF3, therefore with the
growing electron-withdrawing quality of the latter grew
the activity of initial amides in the cyclo-condensation
with H2S and CH2O. It was established that amides with
electron-withdrawing substituents were capable to enter
into the multicomponent condensation with H2S and
CH2O in the absence of BuONa, but in this case the
conversion decreased to 20–30%.
Compounds IIf and IIIf were separated by column
chromatography on SiO2 (eluent – CHCl3–ether–
C2H5OH, 10:1:1).
Condensation of benzamide (Ig) with H2S and CH2O
in a ratio 1:2:3 in water medium at 20–70°C is
accompanied by the hydrolysis of amide Ig to benzoic
acid VIg (60%) (Scheme 4). Under these conditions at
0°C dithiazinane II g and thiazetidine Vg formed only
in minor amounts (11 and 5% respectively). Therewith
in the reaction mixture trithiolane IX and tetrathiepane
VIII were also detected. However the condensation of
compound Ig in the presence of BuONa followed by the
treatment with the mixture H2S–CH2O, 2:3, led to the
We showed formerly [10] that at the decrease in the
basicity of the amino group in the initial amines grew
the efficiency of the cyclothiomethylation, but
diminished the selectivity. The basicity of aromatic and
unsaturated carboxamides is reduced compared to the
aliphatic saturated amides due to the conjugation of the
Scheme 3.
20°C, n =1; 40°C, nav = 4.
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MULTICOMPONENT HETEROCYCLIZATION OF CARBOXAMIDES
193
Scheme 4.
1
10
9
O 6
S
S
2
6
8
11
NH2
S1
2
S
O
5N
N3
13
7
(1) BuONa/BuOH
(2) CH2O + H2S,
3:2
BuOH,
7
N 5
S
S
VIII
O
O
CH2O + 2H2S,
3:2
12
8
7
S
S
4
7'
S
S3
8'
4
13
13'
8
IIg
IX
40oC
9
12
12'
11'
9'
O
O
6
4
Ig
9
+
S
10
5
11
10'
N3
1
VIIg
11
OH
10
Vg
VIg
2
Scheme 5.
exclusive formation of 1,3,5-thiadiazinane VIIg in ~74%
yield.
Unlike benzamide (Ig) acetylsalicylamide (Ih)
presumably due to the ortho-effect [17] reacted with H2S
and CH2O (1:2:3) in BuOH–H2O regioselectively form-
ing 5-acetylsalicyloyl-1,3,5-dithiazinane (IIh) in ~80%
yield.
O
CH3
10
9
CH3
O
1
S
6
O
O8
1'
CH2O + H2S, 3:2
BuONa/BuOH
2
5
6'
NH2
N
S 3
2' 7
5'
4
O
The cyclothiomethylation of α-aminosuccinic acid
monoamide (Ii) with H2S and CH2O under the chosen
optimum conditions (Ii–CH2O–H2S, 1:6:4, 20–40°C)
occurred selectively providing 2,4-bis(1,3,5-dithiazinan-
5-yl)-4-oxobutyric acid (XIi) in ~65% yield (see the table,
Scheme 6). At a higher temperature the initial asparagine
(Ii) formed a crystal hydrate and did not enter into the
cyclothiomethylation. The cyclothiomethylation of
asparagine (Ii) with CH2O–H2S in a ratio 1:3:2 resulted
in a mixture of compounds XIi and Xi in yields 15%
each (see the table), whereas at 0°C exclusively 2-(1,3,5-
dithiazinan-5-yl)-4-succinic acid monoamide (Xi) was
obtained in 40% yield, and at 40°C, bisdithiazinane XIi
in ~42% yield.
O
3'
4'
Ih
IIh
Scheme 6.
12
OH
O
9
10
6
11
4
0oC
S
O
CH2O_
8
N
3
O
5
2
NH2
H2S,
3:2
S
H2N
1
7
Xi
OH
O
17
OH
O
O
16
15
6
14S
NH2
Ii
40oC
8
7
9
N5
S1
10N
13
The structure of compounds obtained IIa–IIe, III–
XI was proved by 1H and 13C, IR spectroscopy, and
GC-MS method.
11
2
4
S
S
12
3
XIi
The mass spectra of compounds IIa, IIb, IIg, and Vg
contained the corresponding molecular ion peaks and the
peaks of fragment ions originating from the successive
elimination from [M]+ of fragments CH2S, CH2SCH2S.
Effect of temperature and the ratio of initial compounds on
yield and composition of reaction procucts in thiomethylation
of asparagine (Ii)
Thus the heterocyclization of aliphatic carboxamides
with H2S and CH2O occurred with best yields in the
presence of BuONa and led to the formation of the
corresponding N-acyl-1,3,5-dithiazinanes in high yields.
Benzamide under these conditions gave exclusively 3,5-
dibenzoyl-1,3,5-thiadiazinane in 74% yield, whereas
acetylsalicylamide due to the ortho-effect in BuOH–H2O
mixture formed selectively N-acetylsalicyloyl-1,3,5-
dithiazinane in up to 80% yield.
Temperature,
°C
Ratio of
Ii:CH2O:H2S
Yield, %
Xi
40
15
–
XIi
–
1542
0
20
40
1:3:2
0
20
40
1:6:4
10
–
–
20
30
65
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AKHMETOVA et al.
194
mixed at room temperature (20°C) with BuONa dissolved
EXPERIMENTAL
in BuOH in a molar ratio 1:2, and then was added
dropwise the prepared water solution of CH2O–H2S.
The reaction mixture was stirred for 4 h maintaining the
desired temperature (40°C), then it was neutralized with
dilute HCl. The separated crystals of compounds IIa–
IIe were filtered off, washed with water, and dried.
In experiments were used compounds of purity no
less than 95%. The solvents were purified, dried, and
distilled as described in [18].
1H and 13C NMR spectra were registered on spec-
trometers Bruker AM-300 with operating frequency
300 MHz and Jeol FX 90 Q with operating frequencies
b. Bubbling of H2S through 37% formaldehyde water
solution to a desired reagent ratio was carried out for
1 h. Then to the thiomethylating mixture 1 mol of an
appropriate amide in solution was added dropwise, and
the reaction mixture was stirred for 5 h at a desired
temperature (0, 20, 40, 80°C). The precipitate formed
was filtered off and washed with a large volume of water.
Compounds IIf and IIIf were separated on a column
packed with SiO2 (eluent CHCl3–ether–C2H5OH,
10:1:1).
1
89.55 and 22.50 MHz (for H and 13C respectively),
internal reference TMS. IR spectra were recorded on
a spectrophotometer Specord 75IR from mulls in mineral
oil. Mass spectra of compounds IIa and IIb were
obtained on MKh 1320 instrument with direct admission
of a sample into the ion source at 100–150°C and voltage
70 V. GC-MS analysis of compounds IIg, Vg, and VIg
was carried out on Finnigan 4021 instrument equipped
with a glass capillary column 50000 × 0.25 mm,
stationary phase HP-5, carrier gas helium, ramp from 50
to 300°C at a rate 5 deg/min, vaporizer temperature
280°C, ion source temperature 250°C. Elemental analysis
of the substances was performed on Karlo Erba 1106
analyzer. The melting points were measured on a device
RNMK 80/2617; pH of solutions was determined on
a pH-meter pH-340. Molecular weight of compound IVe
was determined by cryoscopy [19].
5-Formyl-1,3,5-dithiazinane (IIa). Yield 1.86 g
(40%), colorless crystals, mp 84–86°C. IR spectrum, ν,
cm–1: 695, 1085, 1385, 1455, 1600, 2910, 3350. 1H NMR
spectrum (C6D6, CF3COOH), δ, ppm: 2.97 s (2H, H2),
3.62 s (4H, H4,6), 10.50 s (1H, H8). 13C (C6D6,
CF3COOH), δ, ppm: 29.57 t (C2), 50.01 t (C4,6), 161.47 s
(C7). Mass spectrum, m/z (Irel, %): 149 [M]+, 116 [M –
S]+, 102 [M – CH2S]+, 70 [M – SCH2S]+, 56 [M –
CH2SCH2S]+, 42 [CH2=N–N]+. Found, %: C 32.10;
H 4.70; N 9.45; S 43.15. C4H7NOS2. Calculated, %:
C 32.22; H 4.69; N 9.40; S 42.95. M 149.23.
Acetamide complex with sodium butylate in
butanol (A) [CH3CONH2(BuONa)2]. A solution of
1.7 mmol (100 mg) of acetamide (Ib) in butanol was
charged into a reactor containing 5.1 mmol (0.43 ml) of
freshly prepared BuONa in BuOH, and the mixture
obtained was transferred into a cell of IR spectro-
photometer. On adding to the complex A thus obtained
0.05 ml of deuterium oxide the proton signals were
registered. Then under the conditions of continuous
registering 6 drops of acetone were added, and the
13C NMR spectrum was recorded. IR spectrum, ν, cm–1:
650, 1030–1060, 1370–1450, 1610, 1660, 2910, 3300–
3350. 1H NMR spectrum (D2O), δ, ppm: 0.69 t (6H, H4,42
), 1.24 m (8H, H2,22 ,3,32 ), 1.78 s (3H, H3C), 3.35 t (4H,
H1,12 ), 5.19–5.55 br.s (2H, NH2). 13C NMR spectrum
[D2O, (CH3)2CO], δ, ppm: 12.46 m (C4,42 ), 17.93 t (C3,32
), 20.59 t (H3C), 33.85 t (C2,22 ), 60.35 t (C1,12 ), 173.96 s
(CO).
5-Acetyl-1,3,5-dithiazinane (IIb).Yield 1.24 g (35%),
colorless crystals, mp 111–113°C. IR spectrum, ν, cm–1:
700, 1100, 1380–1460, 1660, 2900. 1H NMR spectrum
(DMSO-d6), δ, ppm: 2.55 s (2H, H2), 3.15 s (4H, H4,6),
3.95 t (3H, H8). 13C NMR spectrum (DMSO-d6), δ, ppm:
34.87 t (C2), 60.73 t (C4,6), 15.50 s (C8), 185.05 s (C7).
Mass spectrum, m/z (Irel, %): 163 [M]+, 120 [M –
CH3CO]+, 78 [SCH2S]+, 57 [M – CH2SCH2SCH2]+, 43
[CH3CO]+. Found, %: C 35.97; H 5.73; N 8.42; S 40.15.
C5H9NOS2. Calculated, %: C 36.78; H 5.56; N 8.58;
S 39.28. M 163.26.
5-Caproyl-1,3,5-dithiazinane (IIc). Yield 1.34 g
(30%), colorless crystals, mp 98–100°C. IR spectrum,
ν, cm–1: 710, 1010, 1185, 1380, 1460, 1540, 1645, 2905.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.29 br.s (3H,
H12), 1.73 br.s (6H, H9,10,11), 2.50 br.s (2H, H8), 2.98 s
(2H, H2), 4.40 s (4H, H4,6). 13C NMR spectrum (DMSO-
d6), δ, ppm: 13.74 t (C12), 24.72 t (C9), 30.87 t (C10),
32.92 t (C8), 34.80 t (C2), 63.23 t (C4,6), 179.67 s (C7).
Found, %: C 48.79; H 7.54; N 5.86; S 29.72. C9H17NOS2.
Calculated, %: C 49.28; H 7.81; N 6.39; S 29.23.
Cyclothiomethylation of carboxamides with H2S
and CH2O. a. Into a glass reactor equipped with
a magnetic stirrer, a reflux condenser, an adapter for gas
input, and a dropping funnel was charged at 40°C 3 mol
of 37% formaldehyde water solution, and it was saturated
with hydrogen sulfide by bubbling the gas through the
solution for 1 h. In another reactor the initial amide was
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MULTICOMPONENT HETEROCYCLIZATION OF CARBOXAMIDES
195
3-Oxo-3-(1,3,5-dithiazinan-5-yl)propionitrile (IId).
Yield 1.34 g (67%), yellow crystals, mp 139–141°C. IR
spectrum, ν, cm–1: 730, 1170, 1375, 1460, 1600, 2300–
2350, 2910, 3360. 1H NMR spectrum (DMSO-d6), δ,
ppm: 2.93 br.s (2H, H2), 3.95 s (2H, H8), 4.25 br.s (2H,
H4), 4.60 br.s (2H, H6). 13C NMR spectrum (DMSO-
d6), δ, ppm: 32.36 t (C8), 32.92 t (C2), 66.68 t (C4,6),
129.21 d (C9), 157.01 s (C7). Found, %: C 37.65; H 4.78;
N 15.10; S 34.46. C6H8N2OS2. Calculated, %: C 38.29;
H 4.26; N 14.89; S 34.04.
ppm: 1.85 s (3H, H10), 3.50 s (2H, H2), 5.70 s (4H, H4,6),
7.87–8.80 m (4H, H3,4,5,6). 13C NMR spectrum (DMSO-
d6), δ, ppm: 14.59 br.s (C10), 33.02 t (C2), 63.39 t (C4,6),
117.42 d (C6), 118.49 d (C4), 128.19 d (C3), 130.31 d
(C2), 134.12 d (C5), 152.94 d (C1), 161.99 s (C7), 172.02
s (C9). Found, %: C 51.17; H 4.16; N 4.98; S 23.39.
C12H13NO3S2. Calculated, %: C 50.86; H 4.62; N 4.94;
S 22.63.
3,5-Bis(acryloyl)-1,3,5-thiadiazinane (IIIf)
obtained by method b (40°C). Yield 54 g (20%), colorless
crystals, Rf 0.53 (eluent CHCl3–ether–C2H5OH, 10:2:1).
13C NMR spectrum (DMSO-d6), δ, ppm: 63.01 t (C2,6),
85.77 t (C4), 126.37 d (C8,8'), 132.11 t (C9,9'), 165.89 s
(C7,72 ). Found, %: C 50.94; H 5.66; N 13.21; S 15.09.
C9H12N2O2S. Calculated, %: C 50.86; H 5.42; N 14.01;
S 16.04.
5-Trifluoroacetyl-1,3,5-dithiazinane (IIe). Yield
3.10 g (95%), colorless crystals, mp 123–124°C. IR
spectrum, ν, cm–1: 690, 1090, 1195, 1375–1465, 2920.
1H NMR spectrum (C6D6, CF3COOH), δ, ppm: 3.90
C (2H, H2), 4.5 c (4H, H4,6). 13C NMR spectrum (C6D6,
CF3COOH), δ, ppm: 34.64 t (C2), 50.12 t (C4,6), 115.01
q (C8, 1JC−F 1231.0 Hz), 160.00 q (C7, 2JC−F 171.0 Hz).
Found, %: C 27.62; H 2.80; N 6.42; S 30.05.
C5H6F3NOS2. Calculated, %: C 27.64; H 2.78; N 6.45;
S 29.52.
3,7-Bis(acryloyl)-1,5-dithia-3,7-diazacyclooctane
(IVf, n = 1) obtained by method b (20°C). Yield 3.15 g
(86%), colorless resinous substance. IR spectrum, ν,
cm–1: 690, 810, 1020, 1110, 1230, 1540, 1660, 2900,
1
5-(Acryloyl)-1,3,5-dithiazinane (IIf) obtained by
method b (40°C). Yield 1 g (40%), colorless crystals,
mp 136–138°C, Rf 0.85 (eluent CHCl3–ether–C2H5OH,
10:2:1). IR spectrum, ν, cm–1: 725, 1020, 1185, 1370–
3330. H NMR spectrum (DMSO-d6), δ, ppm: 4.75 s
(8H, H2C2,4,6,8), 5.71 br.s (2H, H2C10,10'), 6.24 br.s (4H,
H2C11,112 ). 13C NMR spectrum (DMSO-d6), δ, ppm:
39.79 t (C2,4), 40.84 t (C6,8), 127.45 t (C11,112 ), 131.45 d
(C10,102 ), 166.23 s (C9,92 ). Found, %: C 46.10; H 5.50;
N 11.40; S 25.05. M 267±10. C10H14N2O2S2. Calculated,
%: C 46.49; H 5.46; N 10.84; S 24.82.
1
1460, 1540, 1650, 2910, 3300. H NMR spectrum
(DMSO-d6), δ, ppm: 3.86 s (2H, H2), 4.92 s (4H, H4,6),
7.44–7.89 m (3H, H8,9). 13C (DMSO-d6), δ, ppm:
31.07 t (C2), 55.56 t (C4,6), 114.00 t (C9), 126.40 d (C8),
178.20 s (C7). Found, %: C 40.05; H 4.86; N 8.14;
S 37.07. C6H9NOS2. Calculated, %: C 41.12; H 5.18;
N 7.99; S 36.59.
N-Benzoyl-1,3-thiazetidine (Vg) obtained by method
b (20°C). Yield 5%, colorless crystals. Mass spectrum,
m/z (Irel, %): 179 (2) [M]+, 148 (2) [M – S]+, 133 (45)
[M – CH2S]+, 119 (5) [M – CH2SCH2]+, 105 (100) [M –
NCH2SCH2]+, 77 (65) [Ph]+, 46 (8) [M – PhCONCH2]+.
C9H9NOS. Calculated: M 179.23.
N-Benzoyl-1,3,5-dithiazinane (IIg) obtained by
method b (20°C). Yield 0.21 g (11%), colorless crystals,
mp 123–125°C. IR spectrum, ν, cm–1: 600–700, 1010,
Benzoic acid (VIg) obtained by method b (80°C).
Yield 1.05 γ (60%), colorless needle crystals, mp 121–
123°C [20]. IR spectrum, ν, cm–1: 700, 930, 1060, 1180,
1310, 1580, 1680, 1785, 2750, 2810. Mass spectrum, m/
z (Irel, %): 122 (87) [M]+, 105 (100) [M – OH]+, 77 (65)
[Ph]+, 44 (22) [M – Ph]+. Found, %: C 69.05; H 4.45.
C7H6O2. Calculated, %: C 65.85; H 4.92. M 122.12.
1
1115, 1400–1450, 1580, 1610–1650, 2910. H NMR
spectrum (DMSO-d6), δ, ppm: 3.79 s (2H, H2), 4.79 s
(4H, H4,6), 7.53–7.96 m (5H, H9,10,11,12,13). 13C NMR
spectrum (DMSO-d6), δ, ppm: 33.12 t (C2), 63.53 t (C4,6),
127.51 d (C10,12), 128.19 d (C9,13), 131.23 d (C11),
134.32 d (C8), 168.31 s (C7). Mass spectrum, m/z (Irel,
%): 225 (5) [M]+, 148 (2) [M – Ph]+, 121 (7) [M –
PhCO]+, 105 (100) [M –NCH2SCH2SCH2]+, 92 (3)
[SCH2S]+, 77 (70) [Ph]+ , 46 (20) [CH2S]+. Found, %: C
52.78; H 5.01; N 5.93; S 29.06. C10H11NOS2. Calculated,
%: C 53.33; H 4.88; N 6.22; S 28.44. M 225.33.
3,5-Bis(benzoyl)-1,3,5-thiadiazinane (VIIg)
obtained by method a. Yield 1.98 g (74%), colorless
crystals, mp 215–217°C. IR spectrum, ν, cm–1: 720, 1010,
1175, 1365, 1495, 1645, 2920, 3360. 1H NMR spectrum
(C6D6, CF3COOH), δ, ppm: 3.95 s (H2,6), 4.73 s (2H,
H4), 7.42–7.90 m (10H, H8,82 ,9,92 ,10,102 ,11,112 ,12,122 ,13,132 ).
13C NMR spectrum (C6D6, CF3COOH), δ, ppm: 55.66 t
(C2,6), 63.18 t (C4), 127.26 d (C10,102 ,12,122 ), 128.28 d
(C9,92 ,13,132 ), 131.34 d (C11,112 ), 134.27 d (C8,82 ), 166.21 s
5-Acetylsalisyloyl-1,3,5-dithiazinane (IIh) obtained
by method b (40°C). Yield 0.5 g (80%), colorless crystals,
mp 105–107°C. IR spectrum, ν, cm–1: 740, 1010, 1380–
1
1460, 1660, 2910. H NMR spectrum (DMSO-d6), δ,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 2 2008

AKHMETOVA et al.
196
(C7,72 ). Found, %: C 65.19; H 5.27; N 8.48; S 11.73.
C17H16N2O2S. Calculated, %: C 65.38; H 5.13; N 8.97;
S 10.25.
2. Brzozowski, Z., Saczewski, F., and Gdaniec, M. Bioorg.
Med. Chem., 2003, 3673.
3. Wohl, A., Ber., 1886, vol. 19, p. 2344.
4. Aleev, R.S., Dal’nova, Yu.S., and Rafikov, S.R., Dokl.
Akad. Nauk SSSR, 1988, 303, 873.
5. Khafizova, S.R., Akhmetova, V.R., Kunakova, R.V., and
Dzhemilev, U.M., Izv. Akad. Nauk, Ser. Khim., 2003,
p. 1722.
6. Khafizova, S.R., Akhmetova, V.R., Tyumkina, T.V.,
Nadyrgulova, G.R., Kunakova, R.V., Khalilov, L.M., and
Dzhemilev, U.M., Izv. Akad. Nauk, Ser. Khim., 2004,
p. 1652.
7. Khafizova, S.R., Akhmetova, V.R., Korzhova, L.F.,
Khakimova, T.V., Nadyrgulova, G.R., Kunakova, R.V.,
Kruglov, E.A., and Dzhemilev, U.M., Izv. Akad. Nauk, Ser.
Khim., 2005, p. 423.
8. Dzhemilev, U.M., Kunakova, R.V., Khafizova, S.R., Ale-
ev, R.S., Dal’nova, Yu.S., and Khalilov, L.M.,
Neftekhimiya, 2002, vol. 42, p. 382.
9. Akhmetova, V.R., Nadyrgulova, G.R., Khafizova, S.R.,
Khairullina, R.R., Paramonov, E.A., Kunakova, R.V., and
Dzhemilev, U.M., Zh. Org. Khim., 2005, vol. 41, p. 151.
10. Akhmetova, V.R., Nadyrgulova, G.R., Khafizova, S.R.,
Tyumkina, T.V., Yakovenko, A.A., Antipin, M. Yu.,
Khalilov, L.M., Kunakova, R.V., and Dzhemilev, U.M.,
Izv. Akad. Nauk, Ser. Khim., 2006, p. 305.
1,2,4,6-Tetrathiepane (VIII). Yield 10%, mp 95–
1
96°C (95–96°C [8]). H NMR spectrum (DMSO-d6), δ,
ppm: 5.30 s (4H, H3,7), 4.46 s (2H, H5). 13C NMR
spectrum (DMSO-d6), δ, ppm: 37.6 t (C3,7), 36.4 t (C5).
Found, %: C 21.33; H 3.28; S 75.39. C3H6S4. Calculated,
%: C 21.17; H 3.53; S 75.30.
1,2,4-Trithiolane (IX). Yield 40%, mp 74–75°C [8].
1H NMR spectrum, δ, ppm: 4.30 s (H3,5). 13C NMR spec-
trum, δ, ppm: 38.8 t (C3,5). Found, %: C 19.52; H 3.38;
S 77.10. C2H4S3. Calculated, %: C 19.35; H 3.23; S 77.42.
2-(1,3,5-Dithiazinan-5-yl)succinic acid monoamide
(Xi) obtained by method b (0°C). Yield 1.05 g (40%),
colorless crystals, mp 208–210°C. IR spectrum, ν,
cm–1: 750, 1005, 1120, 1300, 1370, 1455, 1620, 1695,
2910, 3350. 1H NMR spectrum (DMSO-d6), δ, ppm:
2.12 s (2H, H1), 2.52 br.s (2H, H3), 2.58 t (1H, H4),
3.94 s (2H, H8), 4.61 s (1H, H12), 4.76 s (4H, H6,10).
13C NMR spectrum (DMSO-d6), δ, ppm: 31.00 m (C3),
32.86 t (C8), 55.81 t (C4), 63.30 d (C6,10), 166.65 s (C2),
172.64 s (C11). Found, %: C 35.71; H 4.85; N 12.15;
S 27.03. C7H12N2O3S2. Calculated, %: C 35.59; H 5.08;
N 11.86; S 27.12.
11. Golodnikov, G.V., Prakticheskie raboty po organi-
cheskomu sintezu (Practical Works on Organic Synthesis),
Leningrad: Izd. Leningrad. Gos. Univ., 1966, p. 174.
12. Nekrasov, D.D., Khim. Geterotsikl. Soedin., 2004, p. 1283.
13. Beletskaya, I.P. and Drozd, V.N., Usp. Khim., 1979, vol. 48,
p. 793.
2,4-Bis(1,3,5-dithiazinan-5-yl)-4-oxobutyric acid
(XIi) obtained by method b (40°C). Yield 1.85 g (65%),
colorless crystals, mp 147–149°C. IR spectrum, ν,
cm–1: 700, 750, 1030, 1120, 1175, 1300, 1360, 1455,
1
14. Reutov, O.A. and Kurts, A.A., Usp. Khim., 1977, vol. 46,
p. 1964.
1615, 1685, 2910. H NMR spectrum (DMSO-d6), δ,
ppm: 2.49 br.s (2H, H2C8), 3.35 br.s (1H, H9), 3.66 s
(2H, H13), 3.78 s (2H, H2), 4.18 s (4H, H11,15), 4.56 s
(4H, H4,6), 5.77 s (1H, H17). 13C NMR spectrum (DMSO-
d6), δ, ppm: 31.91 m (C8), 32.89 t (C13), 33.28 t (C2),
55.03 t (C4), 57.41 t (C11,15), 58.71 t (C6), 63.79 d (C9),
169.29 s (C7), 172.97 C (C16). Found, %: C 33.27;
H 4.74; N 9.23; S 35.67. C10H16N2O3S4. Calculated, %:
C 33.71; H 4.53; N 9.16; S 34.91.
15. Zyryanova, I.A., Baikalova, L.V., Tarasova, O.A., Afo-
nin, A.V., Kukhareva, V.A., Maksimova, M.A., and
Trofimov, B.A. Zh. Obshch. Khim., 2005, vol. 75, p. 1353.
16. Kukushkin, Yu.N., Reaktsionnaya sposobnost’koordina-
tsionnykh soedinenii (Reactivity of Complex Compounds),
Leningrad: Khimiya, 1987, p. 119.
17. Barton, S.D. and Ollis, W.D., Comprehensive Organic
Chemistry, New York: Pergamon Press, 1979.
18. Gordon, A.J. and Ford, R.A., The Chemist’s Companion,
New York, 1972
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