Unexpected formation of 5,5-diethoxy-5H-1,2,3-dithiazoles from 5H-1,2,3-dithiazole-5-thiones

Article abstract of DOI:10.1016/j.mencom.2010.06.010

5H-1,2,3-Dithiazole-5-thiones undergo an unexpected transformation into 5,5-diethoxy-5H-1,2,3-dithiazoles upon treatment with sodium ethoxide; the structure of the products was confirmed by Raman and IR spectra.

Full text of DOI:10.1016/j.mencom.2010.06.010

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 212–214
Unexpected formation of 5,5-diethoxy-5H-1,2,3-dithiazoles
from 5H-1,2,3-dithiazole-5-thiones
Oleg I. Bol’shakov,a Lidia S. Konstantinova,a Rinat R. Aysin,b
Natalia V. Obruchnikova,a Elena D. Lubuzha and Oleg A. Rakitin*a
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5328; e-mail: orakitin@ioc.ac.ru
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 499 135 5085
DOI: 10.1016/j.mencom.2010.06.010
5H-1,2,3-Dithiazole-5-thiones undergo an unexpected transformation into 5,5-diethoxy-5H-1,2,3-dithiazoles upon treatment with
sodium ethoxide; the structure of the products was confirmed by Raman and IR spectra.
1,2,3-Dithiazoles are important compounds among the five-
membered heterocycles containing nitrogen and sulfur atoms
due to their biological activity and interesting chemical trans-
formations.1 Much attention in their chemistry is given to
reactions of 5-arylimino-4-chloro-5H-1,2,3-dithiazoles with
nucleophiles.2 Recently, we have found that 4-substituted
5H-1,2,3-dithiazole-5-thiones 1 under treatment with primary
amines underwent a new transformation into 1,2,5-thiadiazole-
3(2H)-thiones.3 To explore the synthetic utility of thiones 1 we
studied their reactivity towards another strong nucleophile –
ethoxide anion.
position and none of the individual products was isolated from
the reaction mixture. Apparently, the chlorine atom is readily
†
General procedure for the preparation of 5,5-diethoxy-5H-1,2,3-dithiazoles
2. A solution of sodium ethoxide prepared from sodium metal (115 mg,
5 mmol) and absolute ethanol (5 ml) was added to a solution of 1 (1 mmol)
in absolute ethanol (15 ml) at 0 °C. The reaction mixture was stirred at
room temperature for 1.5 h, poured into 1% HCl (100 ml) and extracted
with CH2Cl2 (3×10 ml). The combined extracts were washed with H2O,
dried with MgSO4 and evaporated. The residue was separated by column
chromatography (Silica gel Merck 60, light petroleum–CH2Cl2).
The IR spectra of the studied compounds prepared as KBr pellets and
thin films (for liquid sample) were recorded in the region 300–3500 cm–1,
using a Carl Zeiss Specord M82 spectrophotometer. Raman spectra of all
samples were obtained in the region 100–3500 cm–1, using a laser Raman
spectrometer Jobin-Yvon LabRAM 300. Excitation line was red line at
632.8 nm of a He–Ne laser with 6 mW output power. Theoretical calcula-
tions of the geometry and NCA were performed in Gaussian 03 C.018
program at the DFT level with PBE functional9 and 6-311G(d,p)10 basis
sets. Potential energy distributions were calculated using NCA99 program.11
New compounds were characterised by elemental analysis, 1H and
13C NMR and mass spectra.
Interaction of 4-phenyl-5H-1,2,3-dithiazole-5-thione 1a with
sodium ethoxide in absolute ethanol at room temperature for
1.5 h afforded new product 2a. Compound 2a, a yellow oil with
composition C12H15N2O2S2, according to its mass spectrum,
1
elemental analysis and H and 13C NMR spectra is a product
of formal replacement of thione moiety by two ethoxy groups
1
(Scheme 1). H and 13C NMR spectra showed the presence of
two ethoxy groups, and absence of C=S bond in 2a (no carbon
signals in the region 160–220 ppm).
For 2a: yield 55%, yellow oil. 1H NMR (300 MHz, CDCl3) d: 1.22 (t,
6H, 2Me, J 7.3 Hz), 3.37 (m, 2H, CH2), 3.93 (m, 2H, CH2), 7.40 (m,
3H, Ar), 8.07 (d, 2H, Ar, J 5.9 Hz). 13C NMR (75.5 MHz, CDCl3) d:
14.8 (2Me), 62.8 (2CH2), 127.5, 128.6 and 130.3 (5CH, Ar), 131.3, 143.1
and 155.5 (3Csp2). MS (EI, 70 eV), m/z (%): 269 (M+, 32), 241 (15), 135 (20),
104 (100). IR (KBr, n/cm–1): 2976, 2928 (C–H), 2888, 1540, 1392, 1268,
1136, 1112, 1088, 1072, 1044, 1032, 984, 792, 768, 688, 620. Raman
(n/cm–1): 1538 (C=N), 1266, 622, 569, 492 (S–S). Found (%): C, 53.68;
H, 5.79; N, 5.17. Calc. for C12H15NO2S2 (%): C, 53.50; H, 5.61; N, 5.20.
For 2b: yield 61%, yellow oil. 1H NMR (300 MHz, CDCl3) d: 1.24 (t,
6H, 2Me, J 6.8 Hz), 3.36 (m, 2H, CH2), 3.94 (m, 2H, CH2), 8.24 (s, 4H,
Ar). 13C NMR (75.5 MHz, CDCl3) d: 14.8 (2Me), 63.2 (2CH2), 123.8
(2CH, Ar), 128.3 (2CH, Ar), 137.0, 142.2, 148.4 and 153.5 (4Csp2). MS (EI,
70 eV), m/z (%): 314 (M+, 12), 206 (42), 177 (27), 149 (93). IR (KBr,
n/cm–1): 2976, 2928 (C–H), 1596, 1536, 1528, 1516, 1348, 1168, 1136,
1112, 1088, 1072, 1028, 984, 856, 796. Found (%): C, 45.98; H, 4.53;
N, 9.03. Calc. for C12H14N2O4S2 (%): C, 45.85; H, 4.49; N, 8.91.
For 2c: yield 23%, colourless oil. 1H NMR (300 MHz, CDCl3) d: 1.22
(t, 6H, 2Me, J 7.3 Hz), 3.34 (m, 2H, CH2), 3.91 (m, 2H, CH2), 7.05 (m,
2H, Ar), 8.06 (m, 2H, Ar). 13C NMR (75.5 MHz, CDCl3) d: 14.8 (2Me),
62.9 (2CH2), 115.7 (d, 2CH, Ar, J 21 Hz), 129.8 (2CH, Ar), 116.0, 127.6,
154.6 and 164.0 (d, 4Csp2, J 250 Hz). MS (EI, 70 eV), m/z (%): 287 (M+, 3),
259 (2), 242 (1), 153 (12), 122 (100). IR (KBr, n/cm–1): 2976, 2952, 2928
(C–H), 2888, 1672, 1600, 1504, 1472, 1440, 1392, 1272, 1252, 1236, 1160,
1136, 1112, 1040, 1028, 984, 844, 776. Found (%): C, 49.98; H, 5.03;
N, 4.90. Calc. for C12H14FNO2S2 (%): C, 50.15; H, 4.91; N, 4.87.
Careful investigation of this reaction showed that the best
yield was achieved when 5-fold excess of sodium ethoxide was
used (55% yield). Note that this amount significantly exceeded
the required quantity of the reagent (one or two equivalents).
However, when less amount of the reagent was used, some of
the starting thione 1a remained unchanged (TLC data). The
use of greater excess of EtONa (6, 7 or more equivalents) also
dropped the yield of 2a.
Extention of this reaction to other 1,2,3-dithiazole-5-thiones
1 gave the corresponding 5,5-diethoxy derivatives 2 in moderate
yields† (Scheme 1).
Treatment of 4-chloro-5H-1,2,3-dithiazole-5-thione with sodium
ethoxide in EtOH at room temperature led to its full decom-
OEt
OEt
R
S
R
5 equiv. EtONa
abs. EtOH,
room temperature
N
S
N
S
S
S
1
2
a R = Ph, 55%
b R = 4-O2NC6H4, 61%
c R = 4-FC6H4, 23%
d R = 4-MeOC6H4, 33%
e R = 2-thienyl, 25%
f R = 2-benzofuryl, 32%
Scheme 1
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© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 212–214
Table 1 Raman and IR (in parentheses) salient analytical bands of compounds 2a–7 and their assignment.a
Compound
νS–S
νC–S + νN–S
νC–C + νC–C'
νC=N
νC=X, (X = O, S)
2a
3
4
5
6
490 m (490 m)
467 s (468 m)
488 s (490 m)
499 m (500 m)
486 s (486 w)
488 w (482 w)
566 vw (564 w), 622 m (618 s)
512 s (508 m), 634 m (634 s)
541 s (540 s), 661 s (665 s)
569 m (565 m), 604 m (611 w)
522 m (522 m), 599 s (600 m)
528 w (528 m), 633 m (632 s)
1269 m (1266 m)
1262 vw (1260 s)
1227 m (1230 m)
1270 s (1268 s)
1248 s (1250 s)
1280 m (1276 m)
1539 s (1537 w)
1576 vw (1574 m)
1551 s (1555 s)
1640 m, 1655 m (1640 s, 1656 s)
1644 m, 1676 m (1645 vs, 1680 vs)
1140/1132 s (1136 s)
1501 w (1498 w)
1500 s,1598 s
(1588 s, 1604 s)
1085 s (1098 vs)
7
avw – very weak, w – weak, m – medium, s – strong, vs – very strong.
OEt
region. This mode is of mixed origin, νS–S stretching contribu-
tion to potential energy distribution ranging within 60–75%.
Taking into account large polarizability of sulfur atoms, the
Raman intensity of this mode is expected to be high. The low
frequency region of the experimental Raman spectra of 2a–7
reveals several lines of strong and middle intensity (Table 1).
The line at 482–500 cm–1 is assigned to νS–S stretch, its intensity
is high in the case of 3, 4, 6 and middle in the case of 2a, 5, 7.
Thus, the heterocyclic structure, ascribed to 2a, can be con-
firmed, the NCA results for structure 2a agree well with the
experimental spectrum in particular.
To the best of our knowledge, 5,5-dialkoxy-5H-1,2,3-dithiazoles
are unknown compounds. Similar to 5,5-diethoxy derivatives,
5-substituted 5-alkoxy-5H-1,2,3-dithiazoles were synthesized
by treatment of β-ketoenamines with sulfur monochloride in the
presence of methanol.5 Other spiro azetidin-1,2,3-dithiazoles
are also known.6 The formation of gem-dialkoxy heterocyclic
derivatives was proposed only for 1-methyl-2-(substituted phenyl)-
quinazoline-4(1H)-thiones.7
The plausible mechanism for the formation of 5,5-diethoxy-
5H-1,2,3-dithiazoles 2 from thiones 1 is given in Scheme 2. The
reaction could start with nucleophilic attack of ethoxide anion
at the 5-position of the dithiazole ring followed by its opening
into S–S bond and the formation of thioester 8. The attack of
the second ethoxide anion afforded diethoxy derivative 9 which
can suffer intramolecular cyclization to the 1,2,3-dithiazole by
nucleophilic attack of sulfide ion with extrusion of hydrosulfide
anion.
Ph
Ph
O
Me
O
OEt
N
S
N
S
N
S
S
S
S
2a
3
4
Ph
S
Me
S
Ph
NPh
N
S
N
S
N
S
S
S
S
5
6
7
Figure 1
expelled as a chloride anion on the action of NaOEt as it was
reported for 5-arylimino-4-chloro-5H-1,2,3-dithiazoles.4
Unfortunately, we could not prove the structure of diethoxy
derivatives 2 by X-ray analysis because all 1,2,3-dithiazoles 2
were oils which would vitrify but not crystallize upon deep
cooling.
To elucidate the structure of diethoxy derivatives 2, IR
and Raman spectra of the compound 2a, along with those for
relatives 3–7 (Figure 1) were studied. Quantum-chemical cal-
culations of normal-mode frequencies and eigenvectors (NCA)
in a harmonic approximation and as well as IR intensities for
the free molecules 2a, 4–7 were carried out at the DFT level.
According to the NCA results, the frequency of the stretching
vibration of the S–S bond (νS–S) is situated in the 460–500 cm–1
For 2d: yield 33%, yellow oil. 1H NMR (300 MHz, CDCl3) d: 1.21 (t,
6H, 2Me, J 7.3 Hz), 3.36 (m, 2H, CH2), 3.85 (s, 3H, OMe), 3.93 (m,
2H, CH2), 6.89 (d, 2H, Ar, J 8.8 Hz), 8.03 (d, 2H, Ar, J 8.8 Hz).
13C NMR (75.5 MHz, CDCl3) d: 14.8 (2Me), 55.4 (OMe), 62.7 (2CH2),
113.9 (2CH, Ar), 129.2 (2CH, Ar), 124.0, 143.1, 155.2 and 161.2 (4Csp2).
MS (EI, 70 eV), m/z (%): 299 (M+, 56), 254 (35), 234 (37), 192 (35),
134 (100). IR (KBr, n/cm–1): 2976, 2928 (C–H), 1604, 1512, 1464,
1440, 1300, 1256, 1180, 1136, 1096, 1088, 1072, 1052, 1032, 984, 836,
812. Found (%): C, 52.34; H, 5.83; N, 4.63. Calc. for C12H14N2O4S2 (%):
C, 52.15; H, 5.72; N, 4.68.
For 2e: yield 25%, yellow oil. 1H NMR (300 MHz, CDCl3) d: 1.27 (t,
6H, 2Me, J 7.3 Hz), 3.43 (m, 2H, CH2), 3.96 (m, 2H, CH2), 7.06 (m,
1H, Ar), 7.41 (d, 1H, Ar, J 5.1 Hz), 7.76 (d, 1H, Ar, J 2.9 Hz). 13C NMR
(75.5 MHz, CDCl3) d: 14.8 (2Me), 62.9 (2CH2), 126.8, 127.7, 129.1
(3CH, Ar), 135.0, 142.3, 151.8 (3Csp2). MS (EI, 70 eV), m/z (%): 275
(M+, 14), 201 (15), 110 (100). IR (KBr, n/cm–1): 2976, 2936 (C–H), 1456,
1424, 1260, 1232, 1164, 1136, 1112, 1088, 1076, 1040, 1028, 952, 856,
756, 708, 664, 624, 616. Found (%): C, 43.54; H, 4.83; N, 5.03. Calc. for
C12H14N2O4S2 (%): C, 43.61; H, 4.76; N, 5.09.
For 2f: yield 32%, yellow oil. 1H NMR (300 MHz, CDCl3) d: 1.29 (t,
6H, 2Me, J 7.3 Hz), 3.48 (m, 2H, CH2), 3.98 (m, 2H, CH2), 7.28 (m,
1H, Ar), 7.39 (m, 1H, Ar), 7.43 (s, 1H, Ar), 7.58 (d, 1H, Ar, J 8.1 Hz),
7.67 (d, 1H, Ar, J 8.1 Hz). 13C NMR (75.5 MHz, CDCl3) d: 14.9 (2Me),
63.2 (2CH2), 107.2, 111.7, 122.5, 123.6 and 126.5 (5CH, Ar), 127.8,
142.4, 147.9, 148.4 and 155.6 (5Csp2). MS (EI, 70 eV), m/z (%): 309
(M+, 17), 217 (19), 181 (19), 172 (20), 144 (100). IR (KBr, n/cm–1):
2976, 2956, 2924 (C–H), 1448, 1300, 1260, 1176, 1164, 1144, 1112, 1076,
1048, 1028, 1008, 816, 752, 744, 652. Found (%): C, 54.34; H, 4.83;
N, 4.63. Calc. for C14H15NO3S2 (%): C, 54.35; H, 4.89; N, 4.53.
R
S
R
OEt
O
O
OEt
OEt
N
S
N
S
H
S
S
O
SH
Et
1
8
R
OEt
OEt
S
R
OEt
OEt
S
N
– HS–
S
S
9
N
S
H
2
Scheme 2
This work was supported by the Russian Foundation for
Basic Research (grant no. 08-03-00003a) and the Presidium of
the Russian Academy of Sciences (Programme no. 7).
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Received: 19th February 2010; Com. 10/3471
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