Synthesis of Novel 1,3,5-Dithiazine Derivatives

Article abstract of DOI:10.1023/A:1026151307006

The reactions of benzoylacetylene, propiolic acid, and methyl propiolate with 2,4-dithiobiuret and 1-substituted and 1,5-disubstituted 2,4-dithiobiurets in glacial AcOH in the presence of HC1O₄ or BF₃· Et₂O were used to ob

Full text of DOI:10.1023/A:1026151307006

Russian Journal of General Chemistry, Vol. 73, No. 5, 2003, pp. 789 793. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 5, 2003,
pp. 834 838.
Original Russian Text Copyright
2003 by Glotova, Protsuk, Albanov, Nakhmanovich, Lopyrev.
Synthesis of Novel 1,3,5-Dithiazine Derivatives
T. E. Glotova, N. I. Protsuk, A. I. Albanov, A. S. Nakhmanovich, and V. A. Lopyrev
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, Russia
Received April 4, 2001
Abstract The reactions of benzoylacetylene, propiolic acid, and methyl propiolate with 2,4-dithiobiuret
and 1-substituted and 1,5-disubstituted 2,4-dithiobiurets in glacial AcOH in the presence of HClO or BF
4
3
Et O were used to obtain 2-substituted 4-amino-6-imino-1,3,5-dithiazinium perchlorates or trifluoroborates,
2
respectively.
It is known that phenyl isocyanide dichloride reacts
with 1-aryl-2,4-dithiobiurets in benzene under reflux
to give 5-aryl-4-phenylimino-1,3,5-triazines [1],
whereas the reactions with 1,3,5-trisubstituted 2,4-di-
thiobiurets in similar conditions afford substituted
It was found that propiolic acid (I), its methyl ester
(II), and benzoylacetylene (III) react with 2,4-dithio-
biuret (IV), 1-methyl(phenyl)-2,4-dithiobiurets (V,
VI), 1-methyl-5-phenyl-2,4-dithiobiuret (VII), and
1,5-diphenyl-2,4-dithiobiuret (VIII) in glacial AcOH
at 20 C in the presence of equimolar amounts of
HClO or BF Et O, giving perchlorates IX XVI and
1
,3,5-dithiazines [2]. 1-Alkyl(aryl)-2,4-dithiobiurets
were reacted with aldehydes and ketones in the pre-
sence of dry HCl [3] or ethyl chloroformate [4] to
obtain hexahydro-1,3,5-triazine-4,6-dithiones, whereas
4
3
2
trifluoroborates XVII XIX of 2-substituted 4-R -
2
amino-6-R -imino-1,3,5-dithiaziniums in good yields
1
-aroyl-2-bromoacetylenes with 2,4-dithiobiuret in
[scheme (1)]. The reaction presumably involves
benzene or AcOH form 2-acylmethylene-4,6-diimino-
intermediate formation of ketovinyl sulfide A via ad-
dition of the mercapto group to the electron-deficient
5
,6-dihydro-1,3,5-dithiazines [5].
-carbon atom of the starting activated acetylenes
In the present work we studied reactions of acti-
vated acetylenes with sulfur- and nitrogen-containing
ambident nucleophiles as a potentially convenient
synthetic route to N,S-containing heterocyclic com-
pounds.
I III. The attack of the mercapto group on the con-
jugated C=C bond in intermediate A is accompanied
by intramolecular cyclization and produces 1,3,5-di-
thiazinium salts IX XIX.
(1)
1
2
R = OH (I, IX, X), MeO (II, XI), Ph (III, XII XIX); R = H (IV, IX, XI, XII), Me (V, VII, XIII, XV, XVII), Ph (VI,
3
VIII, X, XIV, XVI, XVIII, XIX); R = H (IV VI, IX XIV, XVII, XVIII), Ph (VII, VIII, XV, XVI, XIX); X = HClO
4
(
IX XVI); BF3 (XVII XIX).
1
The composition and structure of compounds
groups appears as a group of bands at 3050 3450 cm
depending on the nature of substituents R and R .
1
2
IX XIX were proved by elemental analysis (Table 1)
1
13
and H and C NMR and IR spectroscopy (Table 2).
1
The IR spectra of compounds IX XIX show an ab-
The H NMR spectra of compounds IX XIX show
a characteristic A X pattern of CH CH= protons.
1
sorption band at 1680 1720 cm due to unconjugated
2
2
C=O group, and stretching absorption of the NH
Protons of the methylene group to the C=O group
1
070-3632/03/7305-0789$25.00 2003 MAIK Nauka/Interperiodica

790
GLOTOVA et al.
Table 1. 1,3,5-Dithiazinium perchlorates IX XVI and trifluoroborates XVII XIX
Found, %
Calculated, %
Cl (F)
Comp. Yield,
no.
mp,
C
Formula
%
C
H
Cl (F)
N
S
C
H
N
S
IX
X
XI
70
72
72.5 104 106 22.57 3.08 11.45 13.08 20.18 C H ClN O S
163 165 20.01 2.37 11.87 14.01 21.20 C H ClN O S
19.64 2.62 11.62 13.75 20.95
34.65 3.15 9.32 11.02 16.80
22.53 3.13 11.11 13.14 20.03
5
8
3 6 2
172 174 34.27 3.22
9.12 11.26 16.57 C H ClN O S
1
1
12
3
6 2
6
10
3
6 2
XII
XIII
XIV
XV
XVI
XVII
90
82
85
96
92
82
200 202 35.95 3.21
196 198 37.62 3.66
96 98 46.47 3.94
96 97 47.32 4.22
166 168 53.69 3.76
198 200 41.41 3.84 (16.51) 12.07 18.31 C H BF N OS
97 98 49.63 3.84 (14.02) 9.98 15.33 C H BF N OS
170 172 56.63 3.78 (11.41) 8.44 13.02 C H BF N OS
9.36 11.23 17.15 C H ClN O S
36.11 3.28
37.94 3.69
46.21 3.62
47.42 3.95
53.33 3.86
41.50 3.75 (16.42) 12.10 18.44
49.88 3.67 (13.94) 10.27 15.65
56.91 3.92 (11.75) 8.66 13.19
9.71 11.49 17.51
9.35 11.07 16.86
1
1
12
3 5 2
9.24 10.94 16.68 C H ClN O S
1
2
14
3 5 2
8.35
7.64
7.07
9.78 14.92 C H ClN O S
8.04
7.79
6.86
9.51 14.50
9.22 14.05
8.12 12.37
1
7
16
3 5 2
9.08 14.11 C H ClN O S
1
8
18
3 5 2
8.39 12.36 C H ClN O S
2
3
20
3 5 2
1
2
13
3
3
2
2
2
XVIII 83
XIX 70
17 15 3 3
2
3
19
3 3
give a doublet at 2.97 4.07 ppm (3J 6.8 Hz). The
4.5 ppm along the series R = OH, MeO, Ph.
1
AX
methylene proton signal is split into a triplet and
absorbs at 5.28 5.69 ppm. The chemical shifts of
Substituted 1,3,5-dithiazines IX XIX are crystals
or powders. They melt with decomposition and are
stable only as salts. Treatment of salts XIII and XIV
with a 1 N solution of NaOH in DMSO, aiming at
obtaining free bases from the reaction mixture gave
bis(benzoylvinyl) sulfide (XX), 2,4-dithiobiurets V
and VI, and an unidentified compound whose IR spec-
CH CH= protons depend on the nature of substituent
2
1
R . Thus, along the series R = OH, MeO, Ph, the CH2
proton signals shift downfield by 0.9 ppm, and the
CH proton signals, by 0.2 ppm.
The 13C NMR spectra were assigned on the basis
of the spectra of the starting biurets and published
data. The CH carbon absorbs upfield compared with
trum contains a well-defined absorption band at 2130
1
2
150 cm .
the CH carbon, probably, under the effect of two
2
1
adjacent sulfur atoms. Substituents R affect only the
Probably, bis(benzoylvinyl) sulfide (XX) is formed
by scheme (2).
CH2 carbon signals, shifting them downfield by
(
2)
R = Me (XIII), Ph (XIV).
Under the action of bases, the 1,3,5-dithiazine ring
in salts XIII and XIV is cleaved to form a cyclic
transition complex B whose thioamide C C bond is
readily cleaved, affording vinylthiol C. The latter, in
its turn, attacks the electron-deficient -carbon atom
in intermediate E, forming bis(benzoylvinyl) sulfide
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

SYNTHESIS OF NOVEL 1,3,5-DITHIAZINE DERIVATIVES
791
Table 2. Spectral characteristics of 1,3,5-dithiazinium perchlorates IX XVI and trifluoroborates XVII XIX
Comp.
no.
1H NMR spectrum (DMSO-d6),
13C NMR spectrum (DMSO-d6),
C, ppm
IR spectrum (KBr), , cm 1
, ppm
+
IX
X
3195, 3290, 3390 (NH , =N H ), 2.97 d (2H, CH ), 5.28 t (1H, CH), 38.74 (CH), 41.41 (CH ), 169.03, 169.89
2
2
2
2
+
4
6
1
725 (C=O), 1610 (NH), 1510 9.77 s (2H, NH ), 10.00 s (2H, =N H ), (C and C ), 181.72 (C=O)
2
2
(
C=N), 1030 1120 (ClO )
12.87 br.s (1H, OH)
4
+
3205, 3300, 3390 (NH, N H ), 3.08 d (2H, CH ), 5.40 t (1H, CH), 39.18 (CH), 41.30 (CH ), 123.47 136.97
2
2
2
4
6
1
1
720 (C=O), 1630 (NH), 1510 7.28 7.73 m (5H, Ph), 10.39 d (2H, (4C, Ph), 163.84, 170.04 (C and C ),
560 (C=C, C=N), 1040 1110 =N H ), 12.00 s (1H, NHPh), 12.90 br.s 181.53 (C=O)
+
2
(
ClO4)
(1H, OH)
XI
3200, 3300, 3395 (NH ), 1730 3.14 d (2H, CH ), 3.70 s (3H, CH ), 39.07 (CH), 41.60 (CH ), 52.67 (CH ),
(
2
2
3
2
3
C=O), 1620 (NH), 1520 (C=N), 5.41 t (1H, CH), 9.86 s (2H, NH2), 163.95, 170.35 (C4 and C ), 185.15
6
1
050 1110 (ClO4) 9.92 s (2H, NH2) (C=O)
3
XII
3200, 3300 3450 (NH ), 1680 3.88 d (2H, CH , J 6.8 Hz), 5.47 t 38.23 (CH), 45.50 (CH ), 128.53 135.66
2
2
2
3
4
6
(
(
C=O), 1620 (NH), 1500 1600 (1H, CH, J 6.8 Hz), 7.52 7.98 m (5H, (4C, C H ), 169.58, 170.60 (C and C ),
C=C, C=N), 1060 1110 (ClO ) C H ), 9.85 s (2H, NH ), 9.97 s (2H, 195.46 (C=O)
6 5
4
6
5
2
NH2)
3195, 3290, 3380 (NH, NH2), 3.06 s (3H, CH NH), 3.88, 3.84 d (2H, 29.82 (CH ), 38.42 (CH), 45.18 (CH ),
XIII
3
3
2
2
3
1
1
690 (C=O), 1625 (NH), 1520 CH , J 18.5 Hz, J 7.0 Hz), 5.45 t 128.23 135.40 (4C, C H ), 165.56,
2
6
5
3
4
6
580 (C=C, C=N), 1050 1100 (1H, CH, J 7.0 Hz), 7.51 7.99 m (5H, 169.42 (C and C ), 195.14 (C=O)
C H , J 7.6 Hz), 10.03, 10.00 s (1H,
(
ClO4)
6
5
+
NH, NHCH ), 10.36 s (1H, N H)
3
+
2
XIV
XV
3100 3300 (NH, =N H ), 1680 3.98 d (2H, CH , J 6.8 Hz), 5.60 t 38.59 (CH), 45.26 (CH ), 123.41 137.03
2 2 2
4
6
(
(
C=O), 1640 (NH), 1490 1570 (1H, CH, J 6.8 Hz), 7.28 8.02 m (10H, (8C, 2Ph), 164.07, 170.39 (C and C ),
C=C, C=N), 1050 1100 (ClO ) 2C H , J 7.8 Hz), 10.30 s (1H, =NH), 195.34 (C=O)
4
6 5
+
1
0.35 s (1H, N H), 11.95 s (1H, NHPh)
+
3150 3380 (NH, =N H), 1690 3.04 s (3H, CH NH), 3.98 d (2H, CH , 30.34 (CH ), 38.65 (CH), 45.12 (CH ),
3
2
3
2
3
3
(
(
C=O), 1610 (NH), 1500 1550 J 6.9 Hz), 5.60 t (1H, CH, J 6.9 Hz), 122.91 136.47 (8C, 2Ph), 164.46,
4
6
C=C, C=N), 1070 1130 (ClO ) 7.32 8.03 m (10H, 2C H , J 7.8 Hz), 166.32 (C and C ), 195.16 (C=O)
4
6 5
1
0.78 s (1H, NHCH ), 12.10 s (1H,
3
NHPh)
3020 3280 (NH, N H), 1690 4.07 d (2H, CH , J 6.9 Hz), 5.69 t 39.02 (CH), 45.61 (CH ), 124.48 136.72
+
XVI
2
2
4
(
(
C=O), 1610 (NH), 1450 1560 (1H, CH, J 6.9 Hz), 7.29 8.05 m (15H, (8C, Ph + 2 PhNH), 165.79, 169.92 (C
6
C=C, C=N), 1050 1120 (ClO ) 3C H ), 12.24 br.s (2H, 2 NH Ph)
and C ), 195.67 (C=O)
4
6 5
XVII 3210 3370 (NH, =NH), 1690 3.07 d (3H, CH NH), 3.86 d (2H, CH ), 29.94 (CH ), 38.53 (CH), 45.31 (CH ),
3
2
3
2
(
(
(
C=O), 1625 (NH), 1510 1580 5.47 t (1H, CH), 7.52 7.98 m (5H, Ph), 128.36 135.52 (4C, Ph), 165.68, 169.54
4
6
C=C, C=N), 1000 1100 br 10.03 s (1H, =NH), 10.38 s (1H, (C and C ), 195.28 (C=O)
[BF ] ) NHCH3)
3
XVIII 3219 3386 (NH, =NH), 1677 3.96 d (2H, CH , 3J 6.8 Hz), 5.61 t 38.56 (CH), 45.27 (CH ), 123.38 137.07
2
2
3
4
6
(
(
C=O), 1640 (NH), 1510 1597 (1H, CH, J 6.8 Hz), 7.27 8.02 m (10H, (8C, 2 Ph), 164.01, 170.34 (C and C ),
C=C, C=N), 1055 br ([BF ] ) 2 C H ), 10.32 s (1H, NH), 11.96 br.s 195.36 (C=O)
3
6 5
(1H, NHPh)
XIX
3250 br (NH), 1680 (C=O), 4.05 d (2H, CH , J 6.8 Hz), 5.68 t 39.04 (CH), 45.30 (CH ), 124.19 136.46
2
2
4
1
450 1560 (C=C, C=N), 1000 (1H, CH, J 6.8 Hz), 7.28 8.05 m (15H, (8C, Ph + 2 PhN), 165.40, 169.40 (C
6
1
100 br ([BF ] )
3 Ph), 12.00 br.s (1H, NH)
and C ), 195.31 (C=O)
3
(
XX) and 2,4-dithiobiurets V and VI. The unidentified
thiobiuret as a combination of ambident species
tending to electron delocalization. In this case, the
structure of 1,3,5-dithiazinium perchlorates IX XVI
can be represented by a combination of mesomeric
structures F I, i.e. as a pseudoaromatic cation sta-
reaction product is, probably, carbodiimide D or its
polycondensation products.
The instability of the 1,3,5-thiadiazines free bases
can be explained considering the structure of 2,4-di-
bilized by the ClO counter ion. Binding the bases
4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

792
GLOTOVA et al.
with an acid violates the coplanarity of the 1,3,5-ditia-
zine ring, enhancing its strain and, as a result, leading
to its cleavage.
(88%) of sulfide XX as an amorphous light yellow
powder, mp 142 143 C (from MeOH), E,Z isomer
1
(mp 143 144 C [8]). IR spectrum, , cm : 3053
CH=), 1639 (C=O), 1539 1596 (C=C). 1 C NMR
3
(
In a similar way, the stability of 1,3,5-dithiazinium
trifluoroborates XVII XIX can be explained in terms
of the formation of a stable donor-acceptor complex
involving delocalized lone electron pairs of the hetero-
atoms and the vacant orbital of the boron atom.
spectrum ( , ppm, DMSO-d ): 188.56, 186.31
C
6
(
(
2C=O), 118.44, 122.53 (2 CO CH=), 128.08 148.91
2Ph, 2 SCH=). Found, %: C 73.24; H 4.56; S 10.62.
C H O S. Calculated, %: C 73.46; H 4.76; S 10.88.
18 14
2
The filtrate was acidified with 0.1 N HCl to pH
.5 7.0, the precipitate that formed was filtered off,
EXPERIMENTAL
6
washed with water, and dried in a vacuum to obtain
The IR spectra were measured on a Specord IR-75
1
13
0
5
.12 g of a dark yellow powder. It was stirred with
ml of MeOH at 20 C for 0.5 h, and the undissolved
instrument in KBr. The H and C NMR spectra were
obtained on Bruker-DPX spectrometer 400
a
1
13
material was filtered off and recrystallized from
MeOH to obtain 0.06 g (81%) of dithiobiuret V, mp
[
d .
400.13 MHz ( H) and 100.61 MHz ( C)] in DMSO-
6
156 C (mp 157 C [6]). The methanolic solution was
1
-Substituted and 1,5-disubstituted 2,4-dithio-
slowly evaporated to dryness, the residue was ground
in petroleum ether (fraction with bp 40 60 C) to
obtain 0.05 g of an unidentified light brown com-
pound, mp 96 98 C.
biurets were synthesized by the procedures described
in [6, 7].
2
-Substituted
4-amino-6-imino-1,3,5-dithiazi-
nium salts IX XIX. To a suspension of 0.01 mol of
In a similar way, from perchlorate XIV we ob-
tained 62% of sulfide XX, 15% of 1-phenyl-2,4-dithio-
biuret (VI), mp 178 180 C (mp 180 C [6]), and 12%
of an unidentified reaction product, mp 79 82 C.
2
,4-dithiobiuret IV VIII in 20 ml of glacial AcOH, a
solution of 0.01 mol of compound I III in 15 ml of
AcOH and a solution of 1.93 ml of 40% HClO in
4
1
0 ml of glacial AcOH were added with stirring, after
which the reaction mixture was stirred for 3 h at 20 C.
The oily yellow solution was poured into 100 ml of
absolute diethyl ether, the mixture was stirred for 1 h,
and the precipitate that formed was filtered off and
dried in a vacuum.
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1
. Pathe, P.P. and Paranjpe, M.G., Indian J. Chem., Sect.
B, 1981, vol. 20, no. 9, p. 824.
Reaction of 1,3,5-thidiazinium salts XIII and
XIV with sodium hydroxide. To a solution of 0.38 g
of perchlorate XIII in 5 ml of DMSO, cooled to
2. Pathe, P.P. and Paranjpe, M.G., J. Indian Chem. Soc.,
1984, vol. 61, no. 2, p. 149.
3
. Faireull, A.E.S. and Peak, D.A., J. Chem. Soc., 1955,
1
0 12 C, we added 3 ml of 1 N aqueous NaOH. The
no. 3, p. 803.
mixture was stirred at 20 C for 1 h, poured into 50 ml
of cold water, and the precipitate that formed was
filtered off and dried in a vacuum to obtain 0.13 g
4. Chande, M.S. and Shetgiri, N.P., J. Indian Chem. Soc.,
1990, vol. 67, no. 11, p. 849.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

SYNTHESIS OF NOVEL 1,3,5-DITHIAZINE DERIVATIVES
793
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. Nakhmanovich, A.S., Glotova, T.E., Komarova, T.N.,
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