Direct synthesis of fused 1,2,3,4,5-pentathiepins

Article abstract of DOI:10.1039/b508186f

Treatment of nucleophilic heterocycles like pyrroles and thiophenes, and their tetrahydro derivatives, with S₂Cl₂ and DABCO in chloroform at room temperature provides a simple one-pot synthesis of fused mono and bispentathiepins. N-Methylpyrrole and its 2-chloro and 2,5-dichloro derivatives and N-methylpyrrolidine all give the same dichloropentathiepin 1a. N-Ethyl, isopropyl and tert-butylpyrrolidine behave similarly; the isopropylpyrrolidine also gives the bispentathiepin 6 which undergoes an intriguing rearrangement to the symmetrical monopentathiepin 1c. N-Methyl and ethyl indole give either 2,3-dichloro derivatives 8 or the pentathiepinoindoles 9, depending upon the reaction conditions. Thiophene and tetrahydrothiophene give the pentathiepin 10. X-Ray crystal structures are provided for the pentathiepins 1a and 1d, and possible reaction pathways are suggested for the extensive cascade reactions reported. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b508186f

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A R T I C L E
Direct synthesis of fused 1,2,3,4,5-pentathiepins
Stanislav A. Amelichev,a Lidia S. Konstantinova,a Konstantin A. Lyssenko,b Oleg A. Rakitin*a
and Charles W. Rees*c
a N. D. Zelinsky Institute of Organic Chemistry, Academy of Sciences, Leninsky Prospect, 47,
119991, Moscow, Russia. E-mail: orakitin@ioc.ac.ru; Fax: 7-095-1355328;
Tel: 7-095-1355327
b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
Vavilov Str., 28, 119991, Moscow, Russia
c Department of Chemistry, Imperial College of Science, Technology and Medicine, London, UK
SW7 2AZ. E-mail: c.rees@imperial.ac.uk; Fax: +44(0)2075945800; Tel: +44(0)2075945768
Received 10th June 2005, Accepted 2nd August 2005
First published as an Advance Article on the web 2nd September 2005
Treatment of nucleophilic heterocycles like pyrroles and thiophenes, and their tetrahydro derivatives, with S2Cl2 and
DABCO in chloroform at room temperature provides a simple one-pot synthesis of fused mono and bispentathiepins.
N-Methylpyrrole and its 2-chloro and 2,5-dichloro derivatives and N-methylpyrrolidine all give the same
dichloropentathiepin 1a. N-Ethyl, isopropyl and tert-butylpyrrolidine behave similarly; the isopropylpyrrolidine also
gives the bispentathiepin 6 which undergoes an intriguing rearrangement to the symmetrical monopentathiepin 1c.
N-Methyl and ethyl indole give either 2,3-dichloro derivatives 8 or the pentathiepinoindoles 9, depending upon the
reaction conditions. Thiophene and tetrahydrothiophene give the pentathiepin 10. X-Ray crystal structures are
provided for the pentathiepins 1a and 1d, and possible reaction pathways are suggested for the extensive cascade
reactions reported.
1c and 6. Clearly the pyrrolidine ring was more reactive than
Introduction
the isopropyl group, probably being initially dehydrogenated
Sulfur is unique among the elements in forming medium to
to the pyrrole ring, followed by pentathiepin fusion. This
large rings of its atoms, which are stable. Several such rings up
unusual reaction could thus provide an attractive route to fused
to S20 are known. The stability of these allotropes can survive
pentathiepins and we have now studied it systematically, to find
the incorporation of a few atoms of other elements, such as
good reaction conditions, to uncover any intermediates which
carbon. In organic chemistry, seven-membered rings with one
could indicate the reaction pathway, and to explore its scope.
carbon–carbon double bond and five contiguous sulfur atoms,
the 1,2,3,4,5-pentathiepins, have so far attracted most attention.1
This is because of their special stability, their existence in natural
Results and discussion
products and their biological activity, and the high energy barrier
for inversion of the chairlike C2S5 ring leading to chirality.
Originally most attention was focused on benzopentathiepins
bearing an aminoethyl group since the first naturally occurring
examples varacin,2 lissoclinotoxin A,3,4 and N,N-dimethyl-7-
(methylthio)varacin5 have strong antimicrobial and antifungal
activity, and selectively inhibit protein kinase C.5 Furthermore,
varacin is highly toxic towards human colon cancer HCT116.2
More recently it was found that 7-methylbenzopentathiepin,
lacking the aminoethyl group, is a potent thiol-dependent DNA
cleaving agent.6 The pentathiepin ring appears to be crucial for
this biological activity.
The reaction of N-methylpyrrole with S2Cl2 and a base was
investigated in detail and dichloropentathiepinopyrrole 1a was
the major product (Scheme 1). Mass spectrometry, HRMS and
microanalysis gave the formula C5H3Cl2NS5; 1a is symmetrical,
showing an N-methyl group in the 1H and 13C NMR spectra in
addition to two different sp2 carbons. The mass spectrum also
showed a major loss of S2, presumably for conversion of the
pentathiepin into the corresponding 1,2,3-trithiole. Structure 1a
was confirmed by X-ray crystallography (see below).
Several synthetic benzopentathiepins are known1 but hete-
rocyclic fused systems are limited to isothiazolo,7 pyrazolo,8
1,3-dithiolo,9 trithiolobenzo10 and 1,2,3-dithiazolocyclopenta11
derivatives. Methods for the synthesis of pentathiepins are very
limited, the most common being treatment of the preformed
o-dithiols and their precursors and salts with disulfur dichlo-
ride, S2Cl2,7 S3Cl2 or S8 in liquid ammonia.13 However, 1,2-
disubstituted starting materials are not always readily available,
especially for heterocycles.
12
Scheme 1
We have found that nucleophilic heterocycles like pyrroles,
indoles and thiophene, and their fully saturated derivatives,
with S2Cl2 and a base in chloroform at room temperature give
heterocyclic fused pentathiepins.14 This unusual reaction was
discovered as follows. We had previously shown that N-isopropyl
groups reacted with S2Cl2 to give N-(1,2-dithiole-3-thiones).15
However when N-isopropylpyrrolidine (Scheme 3) was similarly
treated with S2Cl2 the isopropyl group remained intact but
pentathiepin rings were fused onto the pyrrolidine ring to give
The reaction time and temperature, and the nature and
quantity of base were important for the yield of 1a. Our standard
procedure was to mix the pyrrole (5 mmol), base and S2Cl2 in
chloroform (50 ml) at −35 ◦C and to stir the mixture for 2 d
at the temperature indicated in Table 1 (nearly always room
temperature) followed by a shorter period of heating under
reflux. The final period of refluxing was not essential but it
appears to facilitate the work-up. The conditions and yields
of 1a are given in Table 1. In the absence of base, or with
3 4 9 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Table 1 Reaction of N-methylpyrrole (5 mmol) with disulfur dichloride and a base in chloroform
Reagents
No.
Base/mmol
S2Cl2/mmol
Temperature of stirring/◦C
Reflux time/h
Yield of 1a (%)
1
2
3
4
5
6
7
8
9
Pyridine (2 mmol)
Pyridine (25 mmol)
EtNPri2 (25 mmol)
Et3N (25 mmol)
DABCO (5 mmol)
DABCO (20 mmol)
DABCO (20 mmol)
DABCO (25 mmol)
DABCO (25 mmol)
DABCO (25 mmol)
DABCO (30 mmol)
20
25
25
25
25
25
20
25
25
25
30
20
20
20
20
20
20
20
20
20
0
3
0
0
0
5
0
0
1
0
0
0
12
30
15
29
20
44
21
45
50
27
38
10
11
20
sodium carbonate or HMDS, the yields of 1a were lower than
those shown. Diazabicyclooctane (DABCO) (5-fold excess) was
found to be the most effective base, used with S2Cl2 (5-fold
excess) at room temperature, giving up to 50% of pentathiepin
1a. This pentathiepin was stable to further reaction with S2Cl2
and DABCO mixtures in the same conditions. Since the precise
stoichiometry of these, and the other reactions reported here,
are not yet known, all yields are based on the assumption that
the S2Cl2 is in excess, and are thus minimum values based on
the heterocyclic starting material. In trying to find reaction
intermediates in the synthesis of 1a, we used less than 5-fold
excess of S2Cl2 (entries 1 and 7), but only 1a was found, in lower
yields.
gave the molecular formula C5H5NS5 for 4 and 1H and 13C
NMR confirmed its lack of symmetry. The unsymmetrical
structure of 5 and the position of the polysulfur ring and the
single hydrogen atom were confirmed by NOE and HMBC
experiments. Saturation at 4.18 ppm (CH2 group) or at 1.32 ppm
(Me group) caused no change at 6.42 ppm (CH group of pyrrole),
and there is thus no interaction of these groups through space. A
heteronuclear multiple bond correlation experiment17 confirmed
the position of the pyrrole CH group: there are two intensive
connectivities of the methylene group (4.18 ppm) to C–S and
C–Cl (117.58 and 131.14 ppm), but no connection of the pyrrole
C–H (6.42 ppm) to these carbons which confirms that the C–H
is in the b-position of the pyrrole ring, 5.
In the formation of 1a from N-methylpyrrole, a pentathiepin
ring has been fused to the pyrrole ring and both pyrrole a-
positions have been chlorinated. To see if the pentathiepin fusion
is possible if one or both a-positions are already chlorinated we
treated 2,5-dichloro 2 and 2-chloro derivatives 3 in the same
way, and 1a was again formed. When equimolar mixtures of
S2Cl2 and DABCO were in 3, 4, 5 and 6-fold excess over 2, the
yields of 1a were 40, 53, 62 and 70% respectively. Analogously, 3
gave 1a with a 5-fold excess of S2Cl2 and DABCO in 60% yield.
Thus b-substitution of the pyrroles 2 and 3 by S2Cl2 followed by
further substitution at sulfur and cyclisation to give the stable
pentathiepin 1a ring would appear to be a possible reaction
pathway.
A separate experiment showed that the unsymmetrical pen-
tathiepin 5 was converted into the symmetrical pentathiepin
1b by S2Cl2–DABCO in good yield (52%); this is a new and
unexpected rearrangement of a 2,3- to a 3,4-fused pentathiepin
accompanied by ring-chlorination, of considerable mechanistic
significance (see Scheme 8).
As we saw above, N-isopropylpyrrolidine gave an initially
unexpected mixture of two pentathiepins with the N-isopropyl
groups intact, dichloromonopentathiepin 1c and the bispen-
tathiepin 6 (Scheme 3). The latter, a yellow oil, is believed to
be the first bispentathiepin reported. Both are symmetrical, and
their structures were confirmed by their spectroscopic properties
and the X-ray crystal structure determination of 1c.
Since S2Cl2 could also, in principle, oxidize the pyrrolidine
to pyrrole, we studied the same reaction of N-alkyl derivatives
of pyrrolidine, which are readily available from the reaction
of dichloro- or dibromobutanes and corresponding amines.16
N-Methyl-, N-ethyl, N-isopropyl- and N-tertbutyl-pyrrolidines
all gave the corresponding N-alkyl dichloropentathiepinopy-
rrole 1 as the main product in low to moderate yield (16–
31%) (Scheme 2). Additionally N-methylpyrrolidine gave a
small amount (5%) of unchlorinated compound 4 with the
pentathiepin ring fused across the 2,3-pyrrole bond and N-
ethylpyrrolidine gave rather more (23%) of a similarly fused
product 5 but now chlorinated in the free a-position of pyrrole
(Scheme 2). The spectral data of 1b, c and d were similar
to those of 1a. Mass spectrometry, HRMS and microanalysis
Scheme 3
Separate experiments showed that 6 was also converted
into 1c by S2Cl2–DABCO in high yield (78%) and 1c was
unchanged by further treatment. This conversion of 6 into 1c
is presumably mechanistically related to the rearrangement of
the monopentathiepin 5 to 1b above. A possible mechanism is
proposed (Scheme 9).
With N-tert-butylpyrrolidine, the only fully characterised
product was the dichloropentathiepin 1d (31%); the bispen-
tathiepin 7, analogous to 6, was detected in traces and its
structure was indicated by mass and HMRS spectra (Scheme 4).
Structurally similar N-alkylindoles, with only the 2,3-indole
bond available for pentathiepin fusion, were also treated with
Scheme 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1
3 4 9 7

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◦
˚
Table 2 Selected bond lengths (A) and angles ( ) in crystals of 1a and
1d
1a
1d
S(1)–S(2)
S(2)–S(3)
S(3)–S(4)
S(4)–S(5)
S(1)–C(2)
S(5)–C(3)
Cl(1)–C(1)
Cl(2)–C(4)
N(1)–C(1)
N(1)–C(4)
N(1)–C(5)
C(1)–C(2)
C(2)–C(3)
2.053(1)/2.051(1)a
2.056(1)/2.050(1)
2.044(1)/2.053(1)
2.059(1)/2.055(1)
1.735(3)/1.739(3)
1.740(3)/1.740(3)
1.705(3)/1.705(3)
1.705(3)/1.705(3)
1.360(4)/1.369(4)
1.363(3)/1.375(4)
1.470(4)/1.468(4)
1.366(4)/1.363(4)
1.435(4)/1.425(4)
1.361(4)/1.369(4)
2.0527(8)
2.0558(8)
2.0579(8)
2.0587(7)
1.743(2)
1.746(2)
1.709(2)
1.709(2)
1.389(2)
1.386(2)
1.526(2)
1.372(3)
1.426(3)
1.375(3)
Scheme 4
S2Cl2–DABCO in the same way. However the major prod-
ucts from the N-methyl- and N-ethyl compounds were the
2,3-dichloroindoles 8a, b (75 and 78%) (Scheme 5); some
unchlorinated pentathiepin 9b was formed in the case of N-
ethylindole but in very low yield (8%). But with a deficiency
of S2Cl2 (0.8 equiv) and in the absence of a base the only
products were unchlorinated pentathiepins 9 in 70 and 72%
yields. The reactions of Scheme 5 underline the influential
role of the base DABCO, possibly resulting from complexes
formed between it and S2Cl2 e.g. 11 and 12. No characterisable
products were obtained when N-unsubstituted indole, as well as
N-unsubstituted pyrrole and pyrrolidine, were treated similarly
with S2Cl2–DABCO. Possibly the first step in these reactions
is sulfuration of the N–H bond followed by decomposition or
oligomerisation. The parent pentathiepinoindole (9, R = H) has
been reported as a minor product (4%) when isatin was heated
with P4S10 in pyridine.18
C(3)–C(4)
C(2)–S(1)–S(2)
S(1)–S(2)–S(3)
S(2)–S(3)–S(4)
S(3)–S(4)–S(5)
C(3)–S(5)–S(4)
C(1)–N(1)–C(4)
C(1)–N(1)–C(5)
103.8(1)/103.3(1)
104.14(5)/104.74(5)
105.03(5)/104.04(5)
104.86(5)/102.7(1)
102.70(9)/106.8(2)
106.7(2)/106.8(2)
126.9(3)/126.2(3)
104.47(7)
104.64(3)
103.54(3)
103.97(3)
104.85(7)
105.07(15)
123.94(15)
a For 1a bond lengths and angles are listed for two independent
molecules.
ring fused across the 3,4-thiophene bond, has previously been
prepared from 3,4-dibromothiophene by conversion into the 3,4-
dithiol followed by S2Cl2 treatment in 2% overall yield.7
Unexpectedly benzo[b]thiophene did not react with S2Cl2–
base mixtures.
The structures of 1a and 1d were confirmed by X-ray analysis.†
Both pentathiepin rings are characterized by the expected chair-
type conformation (Fig. 1, Table 2). The geometrical parameters
for both compounds are close to the previously investigated,
analogous thienopentathiepin.1,20 The S–S bond lengths vary in
˚
the narrow range of 2.044(1)–2.056(1) A (for two independent
Scheme 5
˚
molecules) in 1a and 2.0527(8)–2.0587(7) A in 1d. The increase
of the inductive effect of the alkyl substituent in 1d leads to some
elongation of the N–C bonds in comparison with those in 1a.
We have tried to extend these S2Cl2 reactions to oxygen
and sulfur nucleophilic five membered heterocycles, and their
tetrahydro derivatives, with more limited success. Furan and
THF decomposed under the reaction conditions, probably
with opening of the oxygen ring, as was found for THF.19
Thiophene gave a mixture of oligomers with no pentathiepin
products; apparently the ring is very reactive towards S2Cl2
and about half of its hydrogen atoms appeared, from NMR
spectra, to be substituted by sulfur. A reduced ratio of S2Cl2 and
DABCO did not improve the situation but simply gave similar
oligomers in lower yield. However, replacement of DABCO
by N-ethyldiisopropylamine in the thiophene reaction did give
unsymmetrical pentathiepinothiophene 10 but only in low yield
(Scheme 6); triethylamine as the base resulted in complete
decomposition of thiophene. Tetrahydrothiophene gave a higher
yield of 10 than thiophene, and the yield increased as the mixture
of S2Cl2 and DABCO was reduced, from a 6-fold excess (24%)
to a 4-fold excess (39%), which suggests the possible conversion
of 10 by these reagents to the mixture of oligomers; this was
confirmed by a blank experiment.
Fig. 1 General view of one independent molecule in 1a and of 1d with
thermal ellipsoids (p = 50%).
Analysis of the packing in both crystals showed that the
molecules are assembled into centrosymmetric dimers. The
intermolecular contacts in 1a and 1d have revealed that in these
dimers, sulfur atoms S(2) and S(4) participate in shortened con-
tacts with chlorine and the pyrrole p-system of the neighbouring
molecule with the S(2) · · · Cl(2A) and S(4) · · · C(1A) distances
Scheme 6
The unsymmetrical nature of 10 followed from its spectro-
scopic properties which were similar to those of the analogous
pyrrole 4. The symmetrical isomer of 10, with the pentathiepin
† CCDC reference numbers 274835 and 274836. See http://dx.doi.org/
10.1039/b508186f for crystallographic data in CIF or other electronic
format.
3 4 9 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1

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˚
varying in the range of 3.595(1)–3.620(1) A and 3.447(3)–
˚
3.467(3) A, respectively see for e.g. (Fig. 2). It is noteworthy that
these contacts are characterized by specific directionality with
the average Cl(2)S(2A)S(1A) and C(1)S(4A)S(5A) angles equal
to 164.5 and 154◦, respectively. In addition to the above contacts,
˚
the S · · · Cl contacts (3.438(1) and 3.469(1) A) between dimers
assembles the molecules into a 3-dimensional framework.
Scheme 7
with opening of the polysulfur ring (see Scheme 8), we also
propose that pentathiepin rings can be built up independently
of other pentathiepins since pentathiepin formation is not always
accompanied by a-chlorination (Scheme 9).
Fig. 2 The formation of dimers in the crystal structures of 1a.
Symmetry code: (A) −x, 1 − y, −z.
To estimate the nature of these contacts we have carried
out the single point calculation of one of the dimers, using
the experimental geometry of the dimer in the crystal of 1d
which is characterized by the shortest S(4) · · · C(1A) distance
˚
(3.466(1) A). The electron density function obtained with the
B3LYP/6-311G* calculation (Gaussian98W program package)
was analyzed in terms of the R. F. Bader “Atoms in Molecule”
(AIM) theory. The charge transfer in terms of the AIM theory
implies the presence of a bond path and thus the presence of
the critical point [CP] (3, −1) of the electron density function
(q(r)) between the corresponding atoms. The critical point search
has revealed the presence of CP (3, −1) for S · · · Cl and S · · · C
contacts, and thus they both correspond to charge transfer from
the chlorine lone pair or pyrrole p-system to antibonding S–S
orbitals. It should be noted that the values of the electron density
Scheme 8
function in the CP (3, −1) for S · · · Cl and S · · · C contacts are
−3
˚
both 0.043 e A which in turn means that the energies of these
interactions are comparable.
Possible reaction pathways
The various fairly complex cascade reactions described above
convert simple saturated and aromatic heterocycles into poly-
cyclic pentathiepins and their chlorinated and rearranged
derivatives; this strikingly illustrates the extensive reactivity of
S2Cl2 and its complexes with bases, particularly DABCO.21 This
reactivity encompasses dehydrogenation of tetrahydroaromat-
ics, the chlorination and sulfuration of aromatics and their
conversion into –SSCl derivatives,22 pentathiepin ring formation
and pentathiepin to pentathiepin rearrangements. We have also
proposed20 that –SnCl chains can be extended to give –S(n + 1)Cl
chains by the addition of S2Cl2 and loss of SCl2 (see Scheme 7) to
give ultimately the thermodynamically stable1 pentathiepin ring.
Too little is known as yet about the nature and timing of all these
steps to give precise reaction mechanisms, but possible overall
reaction pathways are suggested in Schemes 7–9,23 where X
represents a nucleophilic heteroatom and S2Cl2 includes possible
S2Cl2–base complexes such as 11 and 12.21 In Scheme 9 the
final cyclisation could have occurred earlier in the sequence.
Scheme 9 shows two possible routes from bispentathiepins
to the new monopentathiepin. In addition to this unexpected
reaction, initiated by ipso chlorination of the 5-membered ring
Scheme 9
All these cascade reactions show how readily and uniquely
thermodynamically stable 1,2,3,4,5-pentathiepin rings can be
fused onto certain heterocyclic rings in one-pot reactions and
suggest many possible extensions of this simple procedure.
Experimental
Melting points were determined on a Kofler hot-stage apparatus
and are uncorrected. IR spectra were recorded on a Specord
1
M-80 instrument in KBr pellets. H NMR were recorded on
a Bruker WM 250 spectrometer (250 MHz) and 13C NMR
spectra were recorded on a Bruker AM 300 (75.5 MHz) in CDCl3
solution. CH groups were identified by DEPT experiments. J-
values are given in Hz. Mass spectra were recorded on a Finnigan
MAT INCOS 50 instrument using electron impact ionisation.
Light petroleum refers to the fraction bp 40–60 ◦C.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1
3 4 9 9

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Table 3 Crystallographic data for 1a and 1d†
1a
1d
Formula
M
T/K
C5H3Cl2NS5
308.28
C8H9Cl2NS5
350.36
110
Monoclinic, P21/c
8.731(1)
9.435(1)
298
Triclinic, P1
¯
Crystal system, space group
˚
a/A
8.781(2)
9.148(2)
13.906(3)
79.21(2)
87.89(2)
84.47(2)
1092.0(4), 4
15.00
˚
b/A
˚
c/A
16.064(2)
a/deg
b/deg
93.761(3)
c /deg
3
˚
V/A , Z
1320.5(3), 4
12.52
l/cm−1
F(000)
616
None
1.875
712
Absorption correction
Semiempirical absorption correction from equivalent reflections
1.762
qcalcd/g cm−3
2hmax/deg
Diffractometer
Scan mode
54
60
Siemens P3/PC
h/2h
Smart CCD
x
No. of reflections measured (Rint
No. of independent reflections
No. of reflections with I > 2r(I)
No. of parameters
R1
)
5037 (0.0178)
4741
3411
237
0.0384
0.1022
1.002
0.427/−0.417
6930 (0.0136)
3674
3192
145
0.0362
0.0870
0.978
0.512/−0.446
wR2
GOF
−3
˚
Max/min peak/e A
Crystallographic data for 1a and 1d are presented in Table 3.
Both structures were solved by direct methods and refined by
full-matrix least-squares against F2 in the anisotropic (H-atoms
isotropic) approximation, using the SHELXTL-97 package. The
hydrogen atoms were located in the Fourier electron density
synthesis. All calculations were performed using SHELXTL
PLUS 5.0.
4%), 323 (M+ + 2, 18%), 321 (M+, 20%, found M+, 320.8391.
C6H5Cl2NS5 requires M, 320.8403), 261 (M+ + 4 − S2, 4%), 259
(M+ + 2 − S2, 18%), 257 (M+ − S2, 20%), 64 (S2, 100%).
7-Chloro-6-ethyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]pyrrole 5.
Yellow solid, mp 62–63 ◦C. (Found C, 24.8; H, 2.0; N, 5.2%.
C6H6ClNS5 requires C, 25.0; H, 2.1; N, 4.9%); mmax/cm−1 1480,
1440, 1410, 1380, 1300, 1140, 790 (C–Cl); dH (CDCl3) 6.42
(s, 1H, CH), 4.18 (septet, 2H, J 6.9 and 7.3, CH2), 1.32 (t,
3H, J 7.3, CH3); dC (CDCl3) 131.14, 117.58 and 105.14 (3 sp2
tertiary C), 113.82 (CH), 41.61 (CH2), 16.59 (CH3). m/z (EI) 289
(M+ + 2, 15%), 287 (M+, 28%, found M+, 286.8797. C6H6ClNS5
requires M, 286.8792), 225 (M+ + 2 − S2, 44%), 223 (M+ − S2,
100%).
General procedure for the reactions with S2Cl2 and a base
Disulfur◦dichloride (2.8 ml, 35 mmol) was added dropwise at
−30–35 C to a stirred solution of the substrate (5 mmol) and
DABCO (3.92 g, 35 mmol) dissolved in chloroform (100 ml).
Then the mixture was stirred for 15 min at −20 ◦C and at
room temperature for 48 h. Triethylamine (7.2 ml, 50 mmol) was
added, the mixture was refluxed for up to 3 h, filtered and the
solvent was removed under reduced pressure. The residue was
separated by column chromatography (silica, light petroleum,
and then light petroleum–DCM mixtures).
6,8-Dichloro-7-isopropyl-7H-[1,2,3,4,5]pentathiepino[6,7-c]pyr-
role 1c. Yellow solid, mp 135–139 ◦C. (Found C, 24.7; H,
1.9; N, 4.5%. C7H7Cl2NS5 requires C, 25.0; H, 2.1; N, 4.2%);
mmax/cm−1 2980 (CH), 1480, 1400, 1290, 1180, 1140, 795 (C–Cl);
dH 5.01 (septet, 1H, J 6.5, CH), 1.61 (d, 6H, J 6.5, 2 CH3); dC
115.31 and 78.01 (2 sp2 tertiary C), 52.11 (CH), 21.66 (CH3).
m/z (EI) 339 (M+ + 4, 1%), 337 (M+ + 2, 3%), 335 (M+, 4%,
found M+, 334.8550. C7H7Cl2NS5 requires M, 334.8559), 303
(15), 301 (22), 273 (17), 271 (22), 237 (85), 195 (100).
6,8-Dichloro-7-methyl-7H-[1,2,3,4,5]pentathiepino[6,7-c]pyrrole
◦
1a. Yellow solid, mp 167–170 C. (Found C, 19.8; H, 1.2; N,
4.2%. C5H3Cl2NS5 requires C, 19.5; H, 1.0; N, 4.5%); mmax/cm−1
1460, 1420, 1340, 1100, 780; dH 3.60 (s, 3H, CH3); dC 123.82 and
121.53 (2 sp2 tertiary C), 33.21 (CH3). m/z (EI) 311 [(M+ + 4,
2%, found M+, 306.8238. C5H3Cl2NS5 requires M, 306.8246],
309 (M+ + 2, 6), 307 (M+, 9), 245 (39), 243 (48).
11-Isopropyl-11H-di[1,2,3,4,5]pentathiepino[6,7-b:6,7-d]pyr-
role 6. Yellow oil. (Found C, 19.6; H, 1.8; N, 3.1%. C7H7NS10
requires C, 19.8; H, 1.7; N, 3.3%); mmax/cm−1 2980 (CH), 1440,
1270, 1120; dH 4.84 (septet, 1H, J 7.2, CH), 1.59 (d, 6H, J 7.2, 2
CH3); dC 122.79 and 87.53 (2 sp2 tertiary C), 52.02 (CH), 21.13
(CH3). m/z (EI) 425 (M+, 5%, found M+, 424.7788. C7H7NS10
requires M, 424.7786), 393 (2), 361 (26), 337 (28), 297 (40), 271
(70), 229 (72), 96 (38), 64 (100).
6-Methyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]pyrrole 4. Yellow
solid, mp 99–101 ◦C. (Found C, 24.8; H, 2.4; N, 5.8%. C5H5NS5
requires C, 25.1; H, 2.1; N, 5.9%); mmax/cm−1 1495, 1440, 1360,
1300, 1180, 740; dH 6.58 (d, 1H, J 2.6, CH), 6.48 (d, 1H, J 2.6,
CH), 3.80 (s, 3H, CH3); dC 128.55 and 127.28 (2 sp2 tertiary C),
123.86 and 115.31 (2 × CH), 35.80 (CH3). m/z (EI) 239 (M+,
47%, found M+, 238.9016. C5H5NS5 requires M, 238.9026), 207
(2), 175 (100), 142 (53), 128 (3), 111 (49).
6,8-Dichloro-7-tert-butyl-7H-[1,2,3,4,5]pentathiepino[6,7-c]pyr-
role 1d. Yellow solid, mp 102–104 ◦C. (Found C, 27.7; H,
2.5; N, 3.8%. C8H9Cl2NS5 requires C, 27.4; H, 2.6; N, 4.0%);
mmax/cm−1 1470, 1440, 1370, 1290, 1180, 1040; dH 1.87 (s, 9H,
CH3); dC 124.06 and 123.55 (2 sp2 tertiary C), 65.84 (C–CH3),
31.43 (CH3). m/z (EI) 297 (M+ + 4, 16%), 295 (M+ + 2, 40%),
293 (M+, 45%, found M+, 348.8698. C8H9Cl2NS5 requires M,
348.8716), 233 (M+ + 4 − S2, 34%), 231 (M+ + 2 − S2, 84%),
229 (M+ − S2, 88%), 64 (S2, 96%), 57 (100).
6,8-Dichloro-7-ethyl-7H-[1,2,3◦,4,5]pentathiepino[6,7-c]pyrrole
1b. Yellow solid, mp 103–105 C. (Found C, 22.6; H, 1.8; N,
4.3%. C6H5Cl2NS5 requires C, 22.4; H, 1.6; N, 4.4%); mmax/cm−1
1450, 1380, 1330, 1110, 750 (C–Cl); dH 4.05 (q, 2H, J 7.2,
CH2), 1.36 (t, 3H, J 7.2, CH3); dC 122.81 and 121.65 (2 sp2
tertiary C), 41.98 (CH2), 14.86 (CH3). m/z (EI) 325 (M+ + 4,
3 5 0 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1

View Article Online
2,3-Dichloro-1-methylindole 8a. Yellow solid, mp 55–
57 ◦C. Lit.24 mp 58 ◦C. mmax/cm−1 1520, 1460, 1430, 1360, 1340,
1240, 1000, 740 (C–Cl); dH 7.59 (m, 1H, PhH), 7.25 (m, 3H,
PhH), 3.73 (s, 3H, CH3); dC 135.02, 125.04, 121.92 and 102.63
(4 sp2 tertiary C), 123.40, 121.28, 118.19 and 109.94 (4 × CH),
30.79 (CH3). m/z 203 (M+ + 4, 9%), 201 (M+ + 2, 58%), 199 (M+,
90%, found M+, 198.9961. C9H7Cl2N requires M, 198.9956), 188
(M+ + 4-Me, 10%), 186 (M+ + 2-Me, 78%), 184 (M+ − Me,
100%).
Acknowledgements
We gratefully acknowledge financial support from the Royal
Society, International Science & Technology Centre (grant no.
2117), the Russian Foundation for Basic Research (grant no.
05-03-32032), MDL Information Systems (UK) Ltd and we
thank the Wolfson Foundation for establishing the Wolfson
Centre for Organic Chemistry in Medical Science at Imperial
College. We thank Mr P. Beljakov for expert help with the NMR
spectroscopy.
2,3-Dichloro-1-ethylindole 8b. Yellow oil. (Found C, 55.9;
H, 4.3; N, 6.8%. C10H9Cl2N requires C, 56.1; H, 4.2; N, 6.5%);
mmax/cm−1 2980 (CH), 1480, 1450, 1340, 1220, 1160, 1120, 740
(C–Cl); dH 7.65 (m, 1H, PhH), 7.27 (m, 3H, PhH), 4.25 (q, 2H,
J 7.2, CH2), 1.40 (t, 3H, J 7.2, CH3); dC 133.37, 124.68, 121.84
and 102.19 (4 sp2 tertiary C), 122.72, 120.55, 117.73 and 109.24
(4 × CH), 38.86 (CH2), 14.86 (CH3). m/z 217 (M+ + 4, 10%), 215
(M+ + 2, 55%), 213 (M+, 92%, found M+. C10H9Cl2N requires M,
213.0112), 202 (M+ + 4-Me, 12%), 200 (M+ + 2-Me, 75%), 198
(M+ − Me, 100%).
6-Methyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]indole 9a. Di-
sulfur dichloride (1.2 ml, 20 mmol) was added dropwise at
−30–35 ◦C to a stirred solution of 1-methylindole (2.55 g,
19.5 mmol) dissolved in chloroform (50 ml). Then the mixture
was stirred for 15 min at −20 ◦C and at 0 ◦C for 48 h. The
mixture was refluxed for 3 h, filtered and the solvent was
removed under reduced pressure. The residue was separated
by column chromatography (silica, light petroleum, and then
light petroleum–DCM mixtures) to yield 9a as a yellow solid
(520 mg, 70%), mp 123–125 ◦C. Lit.25 mp 124–125 ◦C. (Found
C, 37.5; H, 2.3; N, 4.9%. C9H7NS5 requires C, 37.3; H, 2.4; N,
4.8%); mmax/cm−1 2980 (CH), 1440, 1330, 1240, 1160, 820, 780,
740; dH 7.70 (m, 1H, PhH), 7.30 (m, 1H, PhH), 3.91 (s, 3H,
CH3); dC 141.84, 137.08, 129.47 and 126.01 (4 sp2 tertiary C),
125.22, 122.70, 119.61 and 111.06 (4 × CH), 32.10 (CH3). m/z
289 (M+, 22%), 225 (100), 192 (42).
References
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6-Ethyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]indole 9b. Yellow
solid, mp 95–97 ◦C. (Found C, 39.3; H, 3.0; N, 4.8%. C10H9NS5
requires C, 39.6; H, 3.0; N, 4.6%); mmax/cm−1 1460, 1420, 1340,
1220, 740 (CCl); dH 7.73 (m, 1H, PhH), 7.29 (m, 1H, PhH),
4.40 (10-tet, 2H, J 7.0 and 7.5, CH2), 1.42 (t, 3H, J 7.5, CH3);
dC 140.37, 135.29, 129.07 and 119.05 (4 sp2 tertiary C), 124.47,
121.92, 120.60 and 110.31 (4 × CH), 39.94 (CH2), 16.10 (CH3).
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Thieno[2,3-f ][1,2,3,4,5]pentathiepin 10. Yellow oil. (Found
C, 22.8; H, 1.0%. C4H2S6 requires C, 23.2; H, 0.8%); mmax/cm−1
3100 (CH), 1360, 1090, 880, 720; dH (acetone-d6) 7.64 (d, 1H, J
5.5, CH), 7.36 (d, 1H, J 5.5, CH); dC 144.75 and 141.47 (2 sp2
tertiary C), 134.05 and 130.16 (2 × CH). m/z 242 (M+, 65%,
found M+, 241.8483. C4H2S6 requires M, 241.8481), 178 (100),
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 9 6 – 3 5 0 1
3 5 0 1