Bis[1,2]dithiolo[3,4-b][4',3'-e][1,4]thiazine-3,5-dione, a planar 1,4-thiazine

Article abstract of DOI:10.1039/a808192a

N-Benzyldiisopropylamine 1 and S₂Cl₂ give the N-benzylbisdithiolothiazine 2, shown by X-ray crystallography to have the typically folded tricyclic structure; 2 is debenzylated by H₂SO₄ to give the title compound 4 which atypically has a rare near-planar 1,4-thiazine ring, gives a blue anion in solution and does not extrude sulfur thermally.

Full text of DOI:10.1039/a808192a

Bis[1,2]dithiolo[3,4-b][4A,3A-e][1,4]thiazine-3,5-dione, a planar 1,4-thiazine
Carlos F. Marcos,a Oleg A. Rakitin,b Charles W. Rees,c Tomás Torroba,a Andrew J. P. Whitec and David J.
Williamsc
a Departamento de Química Orgánica, Facultad de Veterinaria, Universidad de Extremadura, 10071 Cáceres, Spain.
E-mail: ttorroba@unex.es
b N. D. Zelinsky Institute of Organic Chemistry, Academy of Sciences, Leninsky Prospect, 47, 117913 Moscow,
Russia
c
Department of Chemistry, Imperial College of Science, Technology and Medicine, London, UK SW7 2AY
Received (in Liverpool, UK) 21st October 1998, Accepted 17th November 1998
N-Benzyldiisopropylamine 1 and S2Cl2 give the N-benzyl-
bisdithiolothiazine 2, shown by X-ray crystallography to
have the typically folded tricyclic structure; 2 is debenzy-
lated by H2SO4 to give the title compound 4 which atypically
has a rare near-planar 1,4-thiazine ring, gives a blue anion in
solution and does not extrude sulfur thermally.
folded back and partially overlaying the thiazine ring (Fig. 1).
The molecule has crystallographic Cs symmetry about a plane
passing through S(8), N(4), C(9), C(10) and C(13). The fold
angle about the N···S axis of the thiazine ring is 32°, cf. 34° in
the N-ethyl analogue. The pattern of bonding in the thiazine and
dithiole ring systems does not differ significantly from that
observed in the N-ethyl analogue. The molecules pack to form
corrugated sheets (Fig. 2) dominated by strong intermolecular
O···S interactions [3.02 Å]. There are no intersheet interactions
of note.
Treatment of a dilute solution of the N-benzyl compound 2 in
CH2Cl2 with concentrated H2SO4 at 5–10 °C for 5 min gave the
debenzylated compound 4† (orange–red crystals, mp 222–224
°C) in quantitative yield. All its properties, including a broad
N–H absorption at 3474 cm21 and one carbonyl absorption at
1640 cm21 are in agreement with the parent bis[1,2]di-
thiolo[3,4-b:4A,3A-e][1,4]thiazine-3,5-dione structure 4. X-Ray
analysis of the N–H species 4 shows that removal of the N-
benzyl substituent results in a dramatic flattening of the
molecule, the non-hydrogen atoms being co-planar to within
Sulfur–nitrogen heterocycles with a high proportion of heteroa-
toms are of theoretical and, when reasonable syntheses are
available, practical interest in the chemistry of new materials.
We have shown that Hünig’s base and related diisopropyla-
mines are fully sulfurated in both isopropyl groups by S2Cl2 in
one-pot reactions to yield bis[1,2]dithiolo[3,4-b:4A,3Ae]-
[1,4]thiazines (cf. 2, 3)1–4 and bis[1,2]dithiolo[4,3-b:3A,4Ad]-
pyrroles (cf. 6, 8),2,4 new families of stable fully unsaturated
heterocycles which are revealing a rich chemistry.
The N-unsubstituted parent ring systems would be partic-
ularly interesting from the structural point of view, and as
intermediates in the preparation of N-substituted derivatives.
Unfortunately these key compounds could not be prepared
directly from Pri2NH since this is decomposed by S2Cl2.
Presumably the first step in the tertiary amine–S2Cl2 reaction is
oxidation of an isopropyl group to give an iminium ion5 which
reacts further with S2Cl2 to form the 1,2-dithiole ring and
ultimately the tricyclic system. Readily removable groups on
nitrogen, such as acetyl and cyano, which would destabilise the
iminium ion suppress the reaction with S2Cl2.4
We therefore treated N-benzyldiisopropylamine6 1 with
S2Cl2 (10 equiv.) and 1,4-diazabicyclo[2.2.2]octane (DABCO)
(9 equiv.) in 1,2-dichloroethane for 3 d at room temperature.
Formic acid (20 equiv.) was then added and the mixture heated
under reflux for 1.5 h, since this treatment gives cleaner
reactions by facilitating conversion of the 3-chlorodithiolium
salts into dithiole-3-ones. Products 2† [orange crystals, mp
200–202 °C (21%)] and 3† [orange solid, mp 209–210 °C (7%)]
were obtained after chromatography (Scheme 1).
Fig. 1 The molecular structure of 2. The geometry at N(4) is pyramidal, with
the nitrogen atom lying 0.24 Å out of the plane of its substituents.
Structure 2 was confirmed by X-ray crystallography‡ which
shows the molecule (Fig. 1) to have a scorpion-like conforma-
tion very similar to the N-ethyl analogue,4 the benzyl ring being
Bn
N
Bn
N
S
O
O
O
Bn
N
S2Cl2
DABCO
+
S
S
S
S
HCO2H
S
S
S
S
S
S
1
3
2
H2SO4
CH2Cl2
H
O
O
O
O
–
N
N
OH–
S
S
S
S
S
S
S
S
S
S
Fig. 2 Part of one of the corrugated sheets of molecules present in the
crystals of 2. The intermolecular O···S contacts (a) and (b) are both 3.02
5
4
Scheme 1
Å.
Chem. Commun., 1999, 29–30
29

Bn
N
Bn
N
S2Cl2
S
S
DABCO
PhCl
S
S
S
S
1
6
+
–
EtO2C
C N O
7
H
N
Bn
O
O
O
O
N
H2SO4
Fig. 3 The molecular structure of 4.
S
S
S
S
BnCl
S
S
S
S
8
9
0.11 Å with only a 5° fold about the thiazine N···S vector (Fig.
3)§ compared to greater than 30° for its N-alkyl derivatives and
27° for dibenzo-1,4-thiazine (phenothiazine).7 The only sig-
nificant change in the pattern of bonding, compared with 2, is a
small decrease in the C(3A)–N(4) distance and a slight increase
in the C(8A)–S(8) bond length. The molecules pack as
alternating bi-directional p–p stacked tapes, the planes of
adjacent stacks being inclined by 89° (Fig. 4). The tapes are
produced by head-to-tail linking of molecules via pairs of O···S
interactions [3.08 and 3.09 Å], and orthogonal tapes by similar
strength O···S, and weaker S···S, interactions [3.15 and 3.54 Å
respectively]. The N–H hydrogen atom is not involved in any
significant intermolecular interactions, possibly because of its
steric congestion.
Scheme 2
CH2Cl2 at room temperature overnight did now give the
debenzylated compound 9 as yellow crystals [mp 267–268 °C
(decomp.) (58%)]. The structure of 9 is based upon spectro-
scopic data and its almost quantitative reconversion to the N-
benzyl compound 8 with ButOK and BnCl in DMF (Scheme 2).
Unexceptionally, 9 did not give a coloured solution in 0.1
M
aq.
NaOH.
Thus the parent bisdithiolopyrrole 9 and bisdithiolo-1,4-thia-
zine 4 have been prepared in very short sequences from 1.
Whilst the properties of the former are entirely normal, the
thiazine 4 is abnormal in that it is almost planar, it readily gives
a highly coloured anion which is inert to substitution on
nitrogen, and it does not extrude the thiazine sulfur atom on
heating. It is not yet clear how these unusual properties, which
appear to indicate enhanced electronic delocalisation and
stabilisation, result from simply replacing an N-alkyl group by
hydrogen, nor why the analogous compounds with one or two
thiocarbonyl groups should be unstable.
We gratefully acknowledge financial support from the
Dirección General de Enseñanza Superior of Spain (DGES
Project ref. PB96-0101), the NATO Linkage Grant 970596,
MDL Information Systems (UK) Ltd, and an RSC Journals
Grant to O. A. R., and we thank the Wolfson Foundation for
establishing the Wolfson Centre for Organic Chemistry in
Medical Science at Imperial College.
Fig. 4 Part of the array of orthogonally oriented p-stacked tapes present in
the crystals of 4, the mean interplanar separation being ca. 3.4 Å. The
intermolecular O···S and S···S contacts are (a) 3.09, (b) 3.08, (c) 3.15 and (d)
3.54 Å.
The N-H compound 4 readily formed purple solutions of the
lithium or sodium salt 5 by reaction with LiHMDS or NaH in
THF from which a hygroscopic deep purple solid could be
isolated by evaporation. Compound 4, with a UV spectrum of
lmax = 310 nm, e = 8860 in THF, gave a blue solution in aq.
Notes and references
† The structures of all new compounds are based upon IR, MS, HRMS, 1H
and 13C NMR and elemental analysis.
‡ Crystal data for 2: C13H7NO2S5, M = 369.5, orthorhombic, Pnma (no.
62), a = 11.573(3), b = 16.113(1), c = 8.064(1) Å, V = 1503.7(4) Å3, Z
= 4 (the molecule has crystallographic Cs symmetry), Dc = 1.632 g cm23
m(Cu-Ka) = 71.3 cm21, F(000) = 752, T = 293 K; orange hexagonal
prisms 0.58 3 0.43 3 0.40 mm. For 4: C6HNO2S5, M = 279.4, monoclinic,
C2/c (no. 15), a = 11.323(1), b = 8.071(1), c = 20.066(2) Å, b =
104.49(1)°, V = 1775.4(3) Å3, Z = 8, Dc = 2.090 g cm23, m(Mo-Ka) =
12.7 cm21, F(000) = 1120, T = 203 K; orange–red blocky needles 0.73 3
0.22 3 0.17 mm. 1232 (2601) Independent reflections were measured on
Siemens P4/PC diffractometers using w-scans for 2 (4) respectively. The
structures were solved by direct methods and all of the non-hydrogen atoms
were refined anisotropically using full-matrix least-squares based on F2
with absorption corrected data to give R1 = 0.036 (0.037), wR2 = 0.093
(0.078) for 1118 (2063) independent observed reflections [|Fo| > 4s(|Fo|),
2q @ 124° (60°)] and 104 (131) parameters for 2 (4) respectively. CCDC
182/1095.
0.1
M
NaOH with lmax = 600 nm, e = 8000. The aqueous
,
alkaline solution was stable for a few days, and the blue spot
formed by immersion of TLC plates in aq. NaOH provides a
good method of detection of 4.
Compound 4 and its sodium salt 5 either did not react with
common electrophiles such as BnCl, BzCl, MeI and TMSCl
under standard conditions or gave unstable products which
reverted to 4 during isolation. In striking contrast with its N-
alkyl derivatives,2,4 4 did not extrude sulfur on heating in
chlorobenzene for 6 h or in 1,2-dichlorobenzene for 2 h. The
expected product 9 (below) was made alternatively. Attempted
thiation of 4 with Lawesson’s reagent in refluxing THF gave an
unstable product that decomposed on work-up; debenzylation
of the oxothione 3 by sulfuric acid also gave an unstable
product, and we have not yet succeeded in preparing thiocarbo-
nyl derivatives of the parent structure 4.
Treatment of 1 with S2Cl2 (10 equiv) and DABCO (10 equiv)
in chlorobenzene for 3 d at room temperature followed by
heating under reflux for 2 h gave the pyrrole 6† [black crystals,
mp 223–224 °C (13%)] (Scheme 2) formed by selective sulfur
extrusion from the intermediate 1,4-thiazine.2,4
The pyrrole 6 was not debenzylated by the sulfuric acid
treatment that is so successful with the thiazine 2. Treatment of
6 in THF at 0 °C for 15 min with excess of ethoxycarbonyl
nitrile oxide 7 generated in situ from ethyl chlorooximidoace-
tate and Et3N4 readily gave the corresponding dioxo derivative
8 [yellow crystals, mp 211–213 °C (decomp.) (86%)], a
structure supported by all its analytical and spectroscopic
properties (Scheme 2). The sulfuric acid treatment of 8 in
§ In the thiazine ring the C and N atoms are coplanar to within 0.01 Å with
the S atom lying 0.11 Å and the H atom 0.20 Å out of this plane.
1 C. F. Marcos, C. Polo, O. A. Rakitin, C. W. Rees and T. Torroba, Angew.
Chem., 1997, 109, 283; Angew. Chem., Int. Ed. Engl., 1997, 36, 281.
2 C. F. Marcos, C. Polo, O. A. Rakitin, C. W. Rees and T. Torroba, Chem.
Commun., 1997, 879.
3 C. F. Marcos, O. A. Rakitin, C. W. Rees, L. I. Souvorova, T. Torroba,
A. J. P. White and D. J. Williams, Chem. Commun., 1998, 453.
4 C. W. Rees, A. J. P. White, D. J. Williams, O. A. Rakitin, C. F. Marcos,
C. Polo and T. Torroba, J. Org. Chem., 1998, 63, 2189.
5 For related examples, see: S. L. Schreiber, Tetrahedron Lett., 1980, 21,
1027; T. Netscher and P. Bohrer, Tetrahedron Lett., 1996, 37, 8359.
6 N. C. Deno and R. E. Fruit, J. Am. Chem Soc., 1968, 90, 3502.
7 J. D. Bell, J. F. Blount, O. V. Briscoe and H. C. Freeman, J. Chem. Soc.,
Chem. Commun., 1968, 1656.
Communication 8/08192A
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Chem. Commun., 1999, 29–30