Heteroatom chemistry of cyclic benzopolychalcogenides: Synthesis and characterization

Article abstract of DOI:10.1002/hc.10069

Many benzopolychalcogenides, for example benzotrithioles, benzotetrathiins, and benzopentathiepins were synthesized from corresponding 1,2-benzenedichalcogenols as starting compounds. The stability of the pentathiepin ring toward functional groups was confirmed by use of amino and sulfide groups as substituents in the molecule of benzopentathiepin. Furthermore, the intramolecular interaction between two polysulfide rings was also studied by synthesis of bisbenzotrithiole, 7,7′-diethyl-4,4′-ethylenedioxybis (benzo[1,2-d][1,2,3]trithiole).

Full text of DOI:10.1002/hc.10069

Heteroatom Chemistry
Volume 13, Number 5, 2002
Heteroatom Chemistry of Cyclic
Benzopolychalcogenides: Synthesis
and Characterization
Ryu Sato
Department of Applied Chemistry, Faculty of Engineering, Iwate University,
Morioka, 020-8551, Japan
Received 22 June 2001; revised 22 March 2002
substituents on the benzene ring were synthesized in
ABSTRACT: Many benzopolychalcogenides, for
example benzotrithioles, benzotetrathiins, and ben-
zopentathiepins were synthesized from corresponding
1,2-benzenedichalcogenols as starting compounds.
The stability of the pentathiepin ring toward func-
tional groups was confirmed by use of amino and
sulfide groups as substituents in the molecule of
benzopentathiepin. Furthermore, the intramolecular
interaction between two polysulfide rings was also
studied by synthesis of bisbenzotrithiole, 7,7 0-diethyl-
4,40 -ethylenedioxybis(benzo[1,2-d][1,2,3]trithiole).
good yields by the treatment of 1,2-benzenedithiol or
1,3-benzenedithiol-1,2-thione with elemental sulfur
in liquid ammonia [13–16] (Scheme 1). These re-
actions were explained in the light of sulfurization
by a new species generated from elemental sulfur
in liquid ammonia. Thus, formation of polysulfide
linkages by sulfurization of the thiolate anion gives
pentathiepin, which is the most thermodynamically
stable compound in this reaction system.
Other ring systems such as benzopenthathiocin
and benzotetrathiepin were also obtained by using
elemental sulfur in liquid ammonia (Fig. 2). These
products are stable thermodynamically and can
easily be isolated; especially two compounds, 4,8-
disubstituted benzo[1,2-d;4,5-d’]bis[1,2,3]trithiole
(BBTT) and 6,10-disubstituted[1,2,3]tri-thiolo[5,4-h]-
benzopentathiepin (TBPT), are characterized by
having two polysulfide rings on one of the benzene
ring [17–19].
Based on these successful results, we felt chal-
lenged to effect the synthesis of the benzopolychalco-
genides such as benzotrithiole and benzotriselenole.
These benzopolychalcogenoles are known to be la-
bile and to require kinetic stabilization for their syn-
thesis. We established the synthetic methodology
of several benzotrithioles stabilized kinetically with
bulky substituents at a neighboring position of the
trithiole ring. Thus, many benzotrithioles were syn-
thesized from the corresponding 1,4-disubstituted
2,3-benzenedithiols or the synthetic equivalents,
1,4-disubstituted 1,3,2-benzodithiastannoles, in
C
2002 Wiley Periodicals, Inc. Heteroatom Chem
13:419–423, 2002; Published online in Wiley Interscience
(www.interscience.wiley.com). DOI 10.1002/hc.10069
Cyclic benzopolychalcogenides such as benzopen-
tathiepins [1–4], benzotetrathiins [5], and ben-
zotrithioles [6–7] have been studied by many het-
eroatom chemists in fields of synthetic, structural,
and biological chemistry [8–12] (Fig. 1). We also es-
tablished a synthetic methodology for obtaining ben-
zopenthiepins [13–16] and benzotrithioles [17,18] by
the sulfurization–cyclization of the corresponding
1,2-benzenedithiols or their synthetic equivalents.
For example, several benzopentathiepins having
This paper is dedicated to the late professor Shigeru Oae.
Correspondence to: Ryu Sato; e-mail: rsato@iwate-u.ac.jp.
2002 Wiley Periodicals, Inc.
c
419

420 Sato
FIGURE 1 Typical benzopolysulfides.
satisfactory yields [20,21] (Scheme 2). This result re-
veals that the introduction of two substituents into
the 1- and 4-positions of the benzene ring stabilized
the trithiole ring sufficiently. This methodology led
us to success in syntheses of many benzopolychalco-
genides containing sulfur and/or selenium atoms in
the polychalcogenide ring [22–24] (Fig. 3). These
benzopolychalcogenoles were found to give a new
species, a benzotrichacogenolium radical cation, by
oxidation with an one electron-oxidizing reagent
such as NOPF6.
FIGURE 2 Cyclic polysulfides synthesized by using S8/NH3
(liq).
On the other hand, the chemical properties
of benzopentathiepin were studied in the area of
the synthesis of heterocyclic compounds. Based on
the reactivity of benzopentathiepin, many reactions
were developed to give many kinds of heterocyclic
compounds that included sulfur atoms on the ben-
zene ring, as shown in Scheme 3 [25–33]. These suc-
cesses in the synthesis of cyclic benzopolychalco-
genides and related compounds have allowed us to
study reactions between the polysulfide ring and
a functional group, such as the amino and sulfide
groups. It is well known that a polysulfide ring such
as benzopentathiepin is sensitive to nucleophilic at-
tack, for example by an amine and thiolate anion,
to bring about cleavage of the sulfur–sulfur linkage
as well as in a linear disulfide and the related poly-
sulfides. Thus, there is a significant problem to be
solved: how do the substituents affect the stability of
polysulfide rings such as pentathiepin?
To clarify the effect of a functional group towards
the pentathiepin ring, we synthesized several ben-
zopentathiepins having nucleophilic substituent at
a neighboring position of the pentathiepin ring. We
were able to confirm that the benzopentathiepin is
stable toward cyclic amines such as pyridine and
pyrimidine and also toward the sulfide moiety con-
tained in a thiophene ring [34,35] (Fig. 4). This result
SCHEME 2
FIGURE 3 Benzotrichalcogenoles containing sulfur and/or
selenium.
SCHEME 1
SCHEME 3

Heteroatom Chemistry of Cyclic Benzopolychalcogenides 421
FIGURE 4 Benzopentathiepins having another functional
group.
is noteworthy, because the natural product varacin
has a benzopentathiepin ring in the molecule, to-
gether with an aminoethyl substituent and these sub-
stituents are found to play biologically important
roles, respectively [36–38]. Thus, we were able to
confirm the stability of the pentathiepin ring toward
a nucleophilic functional group containing nitrogen
or sulfur.
Our next interests focused on the intramolecular
interaction of two polysulfide rings linked with a
spacer such as an alkanediyl or an alkanedioxy
group. We succeeded in the synthesis and the
electrochemical characterization of 7,70-diethyl-
4,40 -ethylenedioxybis-(benzo[1,2-d][1,2,3]trithiole)
(BBT), containing two benzotrithiole rings linked
by an ethylenedioxy group [39] (Scheme 4).
FIGURE 5 ORTEP drawing and crystal packing of BBT.
in high yield. A Grignard reagent obtained from 3
was treated with elemental sulfur and then reduced
with NaBH4 under reflux in THF, to give 1,2-bis(4-
ethyl-3-mercaptophenoxy)-ethane (4). The dithiol
4 obtained was converted to 1,2-bis(4-ethyl-2,3-
dimercaptophenoxy)-ethane (5) by ortho lithiation,
sulfurization, and then reduction with NaBH4. Treat-
ment of 5 with thionyl chloride afforded trithiole-2-
oxide (6) and reduction of 6 with sodium iodide in
the presence of HClO4 gave the target bisbenzotrithi-
ole BBT in 32% overall yield.
The structure of BBT was confirmed spectro-
scopically and finally determined by X-ray crystal-
lography (Fig. 5). According to the result of X-
ray crystallography, most bond lengths and angles
and torsion angles of each trithiole ring were sim-
ilar to the previous data for the benzotrithiole ring
[20] (Table 1). It is very interesting that the whole
structure of BBT is linear and that the two ben-
zotrithiole rings are independent of each other.
Based on the results of the crystal structure analysis,
The synthesis of BBT was established as fol-
lows. Tetrabromination of bis[1,2-(4-ethylphenoxy)]
ethane (1) with bromine in CCl4 and then de-
bromination of the resulting 2 using n-BuLi af-
forded bis[1,2-(3-bromo-4-ethylphenoxy)]ethane (3)
˚
TABLE 1 Selected Distances (A) and Angles ( ) of BBT
Bond lengths
S(1) C(9)
1.791 (6)
S(3) C(8)
S(1) S(2)
S(2) S(3)
1.765 (6)
2.057 (3)
2.062 (2)
Bond angles
S(3) C(8) C(9)
S(1) C(9) C(8)
S(2) S(1) C(9)
S(2) S(3) C(8)
S(1) S(2) S(3)
Torsion angles
S(3) S(2) S(1) C(9)
S(1) S(2) S(3) C(8)
120.8 (4)
114.3 (5)
95.2 (2)
93.1 (2)
95.1 (1)
40.3 (2)
39.7 (2)
SCHEME 4

422 Sato
TABLE 2 Redox Potential of BBT
to this result, we concluded that a radical cation
species could be formed electrochemically by the ox-
idation of BBT and this could return to a neutral
molecule by reduction and that each ring of the two
trithioles was oxidized independently.
Based on the results of electrochemistry, the ox-
idation of bisbenzotrithiole BBT was studied us-
ing two equivalents of a one-electron oxidation
reagent. Thus, the oxidation of BBT with NOPF6
in a mixed solvent of CH2Cl2/MeCN yielded the bis-
radical cation BBT2+ as a dark blue powder, which
decomposed at 109.2 C (Scheme 5). The formation
of a bis-radical cation BBT2+ was confirmed by
31P NMR spectroscopy, to show a typical septet peak
BBT
Epa (V)
Epc (V)
E1/2 (V)
0.67
0.57
0.62
0.66
0.57
0.62
at 143.7 ppm (1 JP = 707 Hz) as shown in Fig. 7.
F
ESR spectroscopy of the bis-radical cation BBT2+
showed a broad signal at g = 2.017 G as shown in
Fig. 8, but the superfine structure could not be ob-
served. These results suggest that both benzotrithi-
ole rings were oxidized simultaneously by the one
electron oxidant NOPF6 to form two radical cation
moieties in the molecule.
FIGURE 6 Cyclic voltammogram of BBT.
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