1,2,5-Trithiepin: A 10π-Electron Heteroaromatic System

Article abstract of DOI:10.1021/jo9519625

The unsubstituted 1,2,5-trithiepin (1) has been synthesized from the known 1,2,5-trithiepane (6) through two consecutive Pummerer rearrangements. Proton and carbon NMR spectra were completely analyzed, assigned, and correlated. The protons in 1 are shifted downfield by Δδ = 0.57 ppm for H₃/H₇ (δ = 6.57 ppm) and by 1.10 ppm for H₄/H₆ (δ = 7.24 ppm) relative to the 6,7-dihydro-1,2,5-trithiepin (7). These downfield shifts are comparable to thiophene, thus characterizing 1,2,5-trithiepin (1) as the first multisulfur 10π-aromatic diatropic molecule incorporating a disulfide linkage. 6,7-Dihydro-1,2,5-trithiepin (7) is a dynamic system. Variable-temperature ¹H-NMR measurements of 7 yielded an estimated free energy of activation at the coalescence temperature (227 K) of ΔG^? = 9.83 kcal/mol.

Full text of DOI:10.1021/jo9519625

2432
J . Org. Chem. 1997, 62, 2432-2436
1,2,5-Tr ith iep in : A 10π-Electr on Heter oa r om a tic System
Shou-Nan Ueng, Michael Blumenstein, and Klaus G. Grohmann*
Department of Chemistry, Hunter College, CUNY Graduate Center, 695 Park Avenue,
New York, New York 10021
Received November 3, 1995X
The unsubstituted 1,2,5-trithiepin (1) has been synthesized from the known 1,2,5-trithiepane (6)
through two consecutive Pummerer rearrangements. Proton and carbon NMR spectra were
completely analyzed, assigned, and correlated. The protons in 1 are shifted downfield by ∆δ )
0.57 ppm for H3/H7 (δ ) 6.57 ppm) and by 1.10 ppm for H4/H6 (δ ) 7.24 ppm) relative to the 6,7-
dihydro-1,2,5-trithiepin (7). These downfield shifts are comparable to thiophene, thus characterizing
1,2,5-trithiepin (1) as the first multisulfur 10π-aromatic diatropic molecule incorporating a disulfide
linkage. 6,7-Dihydro-1,2,5-trithiepin (7) is a dynamic system. Variable-temperature 1H-NMR
measurements of 7 yielded an estimated free energy of activation at the coalescence temperature
(227 K) of ∆Gq ) 9.83 kcal/mol.
In tr od u ction
(4) for this compound. 3,7-Dimethyl-4,6-dicarbomethoxy-
1,2,5-trithiepin has been claimed as one of the products
of the gas-phase photolysis of 5-methyl-4-carbomethoxy-
1,2,3-thiadiazole.9 Tetramethylmercapto-1,2,5-trithiepin
has been reported as one of the methylation products
obtained from the tetrathiaoxalate dianion and methyl
iodide,10 but again, clear structural evidence is missing.
In this paper, we wish to report the synthesis and
characterization of the unsubstituted l,2,5-trithiepin
(1).11 As part of our continuing investigation of poten-
tially aromatic 10π-sulfur heterocycles,12 we were inter-
ested in the parent 1,2,5-trithiepin (1), in order to
investigate this molecule as a potentially 10π-hetero-
aromatic system. A comparative proton NMR study of
1 and its dihydrocompound 7 should establish the
theoretically predicted diatropicity of the molecule, in
analogy to the comparison between thiophene and 2,3-
dihydrothiophene. 1,2,5-Trithiepin (1) would thus rep-
resent the first neutral molecule containing a conjugated
system of 10π-electrons in the form of two double bonds
and three sulfur atoms including a disulfide unit. An
interesting related molecule with a conjugated system
of 8π-electrons and a disulfide unit is the known 1,2-
dithiin (5), first reported by W. Schroth13 in 1965.
1,2,5-Trithiepin (1) and its 1,2,3-isomer 2 are of inter-
est as neutral polysulfur isosteres of cyclodecapentaene.
Together with thionin and the dithiocins, the trithiepins
form a series of heterocyclic analogs of cyclodecapentaene
in the same way that thiophene is the monosulfur
isostere of benzene.1,2 Theoretical calculations by
Zahradnik et al. using HMO theory predict for the
trithiepins high-lying HOMO’s and a narrow HOMO-
LUMO gap but state that 1 might be more stable than
isomer 2.3
Several tetrasubstituted and benzoannelated deriva-
tives of 1,2,5-trithiepin have been reported in the litera-
ture;4,5 however, many of these structures were later
found to be incorrect. Boberg, during his detailed study
on the alkaline cleavage of 5-amino-4-chloro-1,2-dithia-
cyclopenten-3-ones, appears to have been the first to
report the formation of several tetrasubstituted 1,2,5-
trithiepins.6 Schaumann and Grabley described the
formation of tetramethyl-1,2,5-trithiepin (3) from phos-
phorus ylides and carbon disulfide;7 however, an X-ray
structure determination by Kunze et al.8 established the
unique 3,5-bis(isopropylidene)-1,2,4-trithiolane structure
Resu lts a n d Discu ssion
The starting material in our synthesis of 1 was the
known 1,2,5-trithiepane (6),14 obtained in 58% yield
through the FeCl3 oxidation of bis(2-mercaptoethyl)
sulfide (Scheme 1). The 60 MHz proton NMR spectrum
of 1,2,5-trithiepane (6) is deceptive, as it exhibits only a
broad singlet at δ ) 3.05 ppm (CDCl3). However, the
300 MHz spectrum showed a narrow ABCD multiplet.
The 13C-NMR spectrum displayed the expected two
resonances at δ ) 37.6 ppm (C3/C7) and at 31.2 ppm (C4/
C5). The signal assignment is based on the long-range
carbon-proton coupling constants.15 Oxidation of 6 with
1 mol of m-chloroperoxybenzoic acid in chloroform at 0
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) For a review see: Field, L.; Tuleen, D. L. The Chemistry Of
Heterocyclic Compounds; Rosowsky, A., Ed.; Wiley-Interscience: New
York, 1972; Vol. 26, Chapter X, D, p 623.
(2) (a) Pauling, L.; Schomaker, V. J . Am. Chem. Soc. 1939, 61, 1769.
(b) Bradlow, H. L.; Vanderwerf, C. A.; Kleinberg, J . J . Chem. Educ.
1947, 24, 433. (c) Longuet-Higgins, H. C. Trans. Faraday Soc. 1949,
45, 173.
(3) Zahradnik, R.; Pa´rka´nyi, C. Collect. Czech. Chem. Commun.
1965, 30, 3016. Zahradnik, R. In Advances in Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Academic Press: New York, 1965; Vol. 5, p 1 ff.
(4) Lust, S.; Mueller, O. W.; v. Schoor, A.; J acobi, E. German Patent
1095582, U.S. Patent 3000780, 1962; Chem. Abstr. 1962, 56 5162.
Sasaki, Y. J apan J P, 48/1494 [73/1494], 18 J an 1973, 2 pp. Brass, K.;
Pfluger, R.; Hornsberg, K. Chem. Ber. 1936, 69B, 80.
(5) Simmons, H. E.; Vest, R. D.; Blomstrom, D. C.; Roland, J . R.;
Cairns, T. L. J . Am. Chem. Soc. 1962, 84, 4746.
(9) Mu¨ller, E.; Meier, H.; Zeller, K. P. Liebigs Ann. Chem. 1972, 766,
32.
(10) J eroschewski, P.; Hansen, P. Z. Chem. 1982, 22(6), 223.
(11) Ueng, S.-N. Ph.D. Thesis, CUNY Graduate Center, 1978.
(12) Grohmann, K.; Semmelhack, C.; Chiu, I.-C. Tetrahedron Lett.
1976, 1251; J . Am. Chem. Soc. 1976, 98, 2005; 169th National Meeting
of the American Chemical Society, April 1975, Philadelphia; American
Chemical Society: Washington, DC, 1975; ORGN 94, Abstract.
(6) Boberg, F. Liebigs Ann. Chem. 1965, 683, 132.
(7) Schaumann, E.; Grabley, F. F. Liebigs Ann. Chem. 1979, 1702.
(8) Kunze, U.; Merkel, R.; Winter, W. Angew. Chem., Int. Ed. Engl.
1982, 21, 291.
S0022-3263(95)01962-1 CCC: $14.00 © 1997 American Chemical Society

1,2,5-Trithiepin
J . Org. Chem., Vol. 62, No. 8, 1997 2433
Sch em e 1
°C formed a crystalline sulfoxide 8 (mp 95-96 °C) in 52%
yield. Pummerer rearrangement16 of the sulfoxide 8 in
refluxing distilled acetic anhydride for 35 min gave the
6,7-dihydro-1,2,5-trithiepin (7) in 20% yield (bp 61.5 °C/
0.06 mm Hg). The same compound was obtained in 17%
yield upon treatment of 1,2,5-trithiepane (6) with N-
chlorosuccinimide in CCl4 at 5 °C followed by triethyl-
amine in dry benzene at 80 °C. 6,7-Dihydro-1,2,5-
trithiepin (7) is a stable colorless oil with the following
spectral characteristics.
The 300 MHz proton NMR spectrum of the dihydro-
trithiepin 7 displayed an interesting feature. The two
CH2 groups, expected to appear as two triplets, were
observed as a triplet at 3.11 ppm (J ) 6 Hz) and as a
broad multiplet at 3.83 ppm.17
A
1H-DNMR study
confirmed our assumption that 7 is a dynamic system.
At -95 °C the signals for both CH2 groups changed into
two separate, well-resolved AB systems with further
coupling (Figure 1). On the basis of the decoalescence
for the δ ) 3.83 ppm signal at 227 K, one can estimate a
free energy of activation for this process of approximately
9.8 kcal/mol.18 Sulfoxidation of 6,7-dihydro-1,2,5-tri-
thiepin (7) gave an uncharacterized sulfoxide that upon
Pummerer rearrangement in distilled acetic anhydride
under argon at 100 °C yielded 1,2,5-trithiepin (1) in 6.1%
yield as an unstable yellow oil. 1,2,5-Trithiepin (1) was
F igu r e 1. Variable-temperature 1H-NMR spectrum of 6,7-
dihydro-1,2,5-trithiepin (7) in CD2Cl2.
purified by low-temperature preparative TLC under
argon. It proved to be pure by GC and GC/MS. The
compound can be stored in dilute solutions under argon
in the freezer. The high-resolution mass spectrum
(13) Schroth, W.; Billig, F.; Langguth, H. Z. Chem. 1965, 5, 353.
Schroth, W.; Billig, F.; Reinhold, G. Angew. Chem., Int. Ed. Engl. 1967,
6, 689. See also: (a) Behringer H.; Meinetsberger E. Liebigs Ann.
Chem. 1981, 1729. (b) Hartke, K.; Pfleging, E. Liebigs Ann. Chem.
1988, 933. (c) Schroth, W.; Hintzsche, E.; Spitzner, R.; Irngartinger,
H.; Siemund, V. Tetrahedron Lett. 1994, 35, 1973. (d) Block, E.; Guo,
C.; Thiruvazhi, M.; Toscano, P. J . J . Am. Chem. Soc. 1994, 116, 9403.
(e) Koreeda, M.; Yang, W. Synlett 1994, 201. (f) Freeman, F.; Kim, D.
S. H. L.; Rodriguez, E. Sulfur Rep. 1989, 9, 207. (g) Schroth, W.;
Hintzsche, E.; Viola, H.; Klose, H.; Boese, R.; Kempe, R.; Sieler, J .
Chem. Ber. 1994, 127, 401. (h) Koreeda, M.; Yang, W. J . Am. Chem.
Soc. 1994, 116, 10793 and references therein.
showed an ion at m/ z ) 147.9474 (calcd for C4H4S3
)
147.947 52). The mass spectrum exhibited in addition
to the molecular ion m/ e ) 148 (30%) significant frag-
mentation peaks at 116 (29, M - 32), 103 (100, M - 45),
84 (46, M - 64), 64 (15, M - 84), 58 (92, M - 90), 57 (49,
M - 91), 45 (86, M - 103). The UV spectrum in ethanol
showed three maxima at λmax ) 263 nm (ꢀ ) 2250), 296
(1720), 353 (1400).
(14) (a) Field, L.; Barbee, R. B. J . Org. Chem. 1969, 34, 36. (b) Field,
L.; Foster, C. H. J . Org. Chem. 1970, 35, 749. (c) Schoberl, A.; Grafie,
A. Liebigs Ann. Chem. 1958, 614, 66.
The proton NMR spectrum of 1 exhibits an AA′XX′
system with HA ) 7.24 ppm (J AX ) 9 Hz) and HX ) 6.57
ppm (J AX ) 9 Hz). The 13C-NMR spectrum showed the
expected two signals at δ ) 128.6 ppm and at 131.5 ppm.
(15) The gated decoupled 13C-NMR spectrum of trithiepan (6) shows
for the high-field signal (31.2 ppm) a triplet of multiplets with J )
140 Hz, while the low-field signal at 37.6 ppm appears as a triplet of
triplets with J ) 140 and 2.6 Hz. The observed low-field coupling
pattern is attributed to the coupling of carbons 3 and 7 next to the
disulfide linkage with the hydrogens attached to them and the
hydrogens on the neighboring carbons. There is no coupling across the
disulfide functionality. In contrast to that, the triplet of multiplets
Ch em ica l Sh ift Assign m en ts
A decision as to whether the proton signal at δ ) 6.57
ppm corresponds to the protons H3 and H7 while the
signal at δ ) 7.24 ppm corresponds to protons H4 and
H6 or vice versa and in the same way the assignment of
the 13C-NMR signal at δ ) 131.4 ppm to C3/C7 and at δ
) 128.6 ppm to C4/C6 can be reached on the basis of the
3
observed for C4/C6 is the result of an additional long-range J CH
coupling across the sulfide group.
(16) (a) Pummerer, R. Chem. Ber. 1910, 43, 1401. (b) Parham, W.
E.; Bharsar, M. D. J . Org. Chem. 1963, 28, 2686. (c) J ohnson, C. R.;
Phillips, W. G. J . Am. Chem. Soc. 1969, 91, 682. For recent reviews
on the Pummerer rearrangement see: Oae, S.; Numatat, T. Isotopes
in Organic Chemistry; Buncel, E., Lee, C. C., Eds.; Elsevier Sci. Publ.
Co.: New York, 1980; Vol. 5, pp 45-102. Russel, G. A.; Mikoi, G. J .
Mechanisms of Molecular Migrations; Thyagarajan, B. S., Ed.; Inter-
science Publ.: New York, 1968; Vol. 1, pp 157-207. DeLucchi, O.;
Miotti, U.; Modena, G. Organic Reactions; Paquette, L. A., Ed.; J ohn
Wiley: New York, 1991; Vol. 6, p 909.
(18) Using a decoalescence temperature of 227 K (-46 °C) for the δ
) 3.83 1H NMR signal and a chemical shift difference between the
H4a/H4b of ∆δ ) 712 Hz, one obtains for 7 ∆Gq ) 9.83 kcal/mol based
on ∆Gq ) 4.57Tc[9.97 + log (Tc/∆δ)]; see: NMR-Spektroskopie; Gu¨nther,
Η., Ed.; Georg Thieme Verlag: Stuttgart, Germany, 1973; p 248.
(17) The 60 MHz 1H NMR of 7 exhibited two clear triplets with J )
6 Hz.

2434 J . Org. Chem., Vol. 62, No. 8, 1997
Ueng et al.
Ch a r t 1
Ta ble 1. P r oton a n d Ca r bon Ch em ica l Sh ifts for
1,2,5-Tr ith iep in (1) a n d Its Dih yd r o Der iva tive 7
following measurements and considerations: The proton-
coupled 13C-NMR spectrum of 1,2,5-trithiepin (1) consists
1
of a doublet centered at δ ) 131.4 ppm with J CH ) 179.7
Hz and a doublet of doublets of doublets centered at δ )
1
2
128.6 ppm with J CH ) 170.4 Hz, J CH ) 10.3 Hz, and
3J CH ) 6.8 Hz. It is reasonable to assume that J CH
)
3
6.8 Hz is the long-range coupling between C4 or C6 and
H6 or H4 across the sulfide part of the molecule.19 With
the further assumption that the corresponding long-range
4
coupling J CH across the disulfide part between C3 and
2
H7 or C7 and H3 is zero and that J CH between C3/C7 and
3
H4 or H6 is close to zero, while J CH for C4 to H ) 6.8
6
Ta ble 2. P r oton Ch em ica l Sh ifts of Selected Su lfu r
Heter ocycles
Hz,20 we assign to carbons 3 and 7, next to the disulfide
part of 1 δ ) 131.4 ppm, and to carbons 4 and 6, R to the
sulfide section of 1, δ ) 128.6 ppm. Partial off-resonance
decoupling experiments identified the protons attached
to C3/C7 and C4/C6 via their 13C-H coupling constants,
thus allowing a unambiguous chemical shift assignment
for all protons and carbons.
The chemical shift assignments for the 6,7-dihydro-
1,2,5-trithiepin (7) were complicated by the fact that the
molecule was dynamic on the basis of variable temper-
ature proton NMR measurements. The proton-coupled
13C-NMR spectrum of 6,7-dihydro-1,2,5-trithiepin (7)
consists of a doublet of quartets centered at δ ) 126.6
1
2
3
ppm with J CH ) 171 Hz and J CH ) J CH ) 5.8 Hz, a
1
doublet of doublets centered at 119.1 ppm with J CH
)
2
176 Hz and J CH ) 3.7 Hz, a triplet of narrow triplets
1
2
with J CH ) 140 Hz and J CH ) 2.1 Hz, and a triplet of
1
2
doublets of narrow triplets with J CH ) 142 Hz, J CH
)
3
2.0 Hz, and J CH ) 6.1 Hz.
A room-temperature 13C-1H one-bond correlation ex-
periment, HMQC,21 connected the carbon signals with the
respective proton resonances as shown in data set 1
(Chart 1). Long-range correlations obtained through an
HMBC22 experiment are summarized in data set 2 (Chart
1).
observations that sp3-13C chemical shifts for carbons
adjacent to a sulfide functionality are generally upfield
from those of carbons next to a disulfide functionality.23
This has also been observed for the 1,2,5-trithiepane (6).15
Most significant are the observed 1H-chemical shift
changes upon going from the 6,7-dihydro-1,2,5-trithiepin
(7) to 1,2,5-trithiepin (1). For comparison, the proton
chemical shifts for a series of related cyclic sulfur
compounds are presented in Table 2.
As is apparent from these data, only very minor proton
chemical shift changes are being observed upon going
from dihydrothiopyran to thiopyran,24 from dihydro-1,4-
dithiin to 1,4-dithiin,25 or from 1,4-dithia-2-cycloheptene
to 1,4-dithia-2,5-cycloheptadiene.26 However, introduc-
Due to the width of the 1H-NMR signal at δ ) 3.83
ppm, no long-range correlations to these protons are
observed in the HMBC experiment.
These measurements together with the considerations
that long-range coupling across the sulfide part of the
molecule is significant while there is no coupling across
the disulfide section yielded the following chemical shift
assignments for the 1,2,5-trithiepin (1) and the 6,7-
dihydro-1,2,5-trithiepin (7) as shown in Table 1. Ad-
ditional support for these assignments comes from the
(19) For comparison the same 3J CH for thiophene is 5.2 Hz: Nuclear
Magnetic Resonance; Atta-ur-Rahman, Eds.; Springer Verlag: New
York, 1986; Table 4.31.
(20) (a) Gassmann, P.; Drewen, H. J . Am. Chem. Soc. 1974, 95, 3002.
(b) Wilson, G.; Albert, R. J . Org. Chem. 1973, 38, 2160. (c) Vilsmeier,
R.; Sprugel, W. Tetrahedron Lett. 1972, 625.
(21) Heteronuclear Multiple Quantum Correlation: Muller, L. J .
Am. Chem. Soc. 1979, 101, 4481.
(22) Heteronuclear Multiple Bond Correlation: Bax, A.; Summers,
M. F. J . Am. Chem. Soc. 1986, 108, 2093.
(23) Barbarella, G.; Dembach, P.; Garbesi, A.; Fava, A. Org. Magn.
Reson. 1976, 8, 108.
(24) Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees,
C. W., Eds.; Pergamon Press Oxford, New York, Toronto, 1984; Vol. 3,
Part 2B, p 885.
(25) Butler, B. S.; Read, J . M., J r.; Goldstein, J . H. J . Mol. Spectrosc.
1970, 35, 83.
(26) Chiu, I.-C. Ph.D. Thesis, CUNY Graduate Center, 1977.

1,2,5-Trithiepin
J . Org. Chem., Vol. 62, No. 8, 1997 2435
reaction mixture was added to 150 mL of an ice-cold saturated
NaHCO3 solution containing 2 mL of a saturated NaHSO3
solution. Extraction with two portions of 100 mL of CHCl3,
washing the organic extracts with 50 mL of a saturated ice-
cold NaCl solution, and drying the chloroform layer over
anhydrous MgSO4 followed by evaporation under reduced
pressure gave 4.1 g of a white solid. Recrystallization from
CCl4
tion of the second double bond into 2,3-dihydrothiophene,
a cyclic vinyl sulfide, which leads to thiophene, the
archetype of aromatic sulfur heterocycles, causes down-
field shifts of 1.43 ppm for the â-protons and 0.99 ppm
for the R-protons.27 The same magnitude of downfield
shifts are observed for the 6,7-dihydro-1,2,5-trithiepin (7)/
1,2,5-trithiepin (1) pair. Protons H3/H7, next to the
disulfide unit, experience a downfield shift by 0.57 ppm,
while protons H4/H6, are shifted downfield by 1.10 ppm.
These data strongly suggest a diamagnetic ring current,
thus characterizing 1,2,5-trithiepin (1) as the first neu-
tral 10π-aromatic multisulfur heterocycle containing a
disulfide unit as part of the cyclic conjugated system. A
comparison with the 8π-electron, potentially antiaromatic
1,2-dithiin (5), first reported by Schroth13 in 1965, is of
interest. This fascinating deep red molecule exhibits
proton chemical shifts at 6.08 and 6.29 ppm.28
gave 2.52 g (50%) of white crystals, mp 95-96 °C (lit.14
mp 95-96 °C).
1H-NMR (CDCl3, ppm) δ: 2.9-3.1 (m, 4 H), 3.35-3.4.5 (m,
2 H), 3.55-3.7 (m, 2 H). IR(CCl4): 1420, 1390, 1025, 1005,
840 cm-1
.
b. With Sod iu m m -P er iod a te. A solution of NaIO4 (2.31
g, 13.2 mmol) in 55 mL of water was added slowly (20 min) to
a stirred solution of 1,2,5-trithiepane (6) (2.0 g, 13.2 mmol) in
150 mL of tetrahydrofuran. The temperature of the reaction
mixture was maintained at 0-3 °C. Stirring was continued
for 3 h at this temperature and for 5 h at room temperature.
An additional 50 mL of THF was added, the suspension was
cooled to 0 °C and filtered, and the solid was washed with two
portions of 50 mL of THF. The filtrate was evaporated under
vacuum yielding a two-phase watery-oily mixture. Extraction
with 50 mL of CHCl3, drying of the organic layer over MgSO4,
and evaporation of the solvent gave a pale yellow crude
sulfoxide 8, which after recrystallization from CCl4 melted at
95-96 °C. Yield of recrystallized material: 0.87 g (40%).
6,7-Dih yd r o-1,2,5-t r it h iep in (7) via P u m m er er R e-
a r r a n gem en t. A solution of 1,2,5-trithiepane 5-S-oxide (8)
(1.52 g, 10 mmol) in 25 mL of distilled acetic anhydride was
refluxed for 35 min. The dark brown mixture was poured into
150 mL of ice-water, stirred for 1 h to hydrolyze the acetic
anhydride, extracted twice with 100 mL of ether, carefully
neutralized with 150 mL of an ice-cold saturated NaHCO3
solution, washed with ice-cold saturated NaCl solution, and
dried over anhydrous MgSO4. The solvent was evaporated,
and the dark oily residue was chromatographed on SiO2 with
hexane, giving 0.29 g (20%) of 6,7-dihydro-1,2,5-trithiepin (6),
bp0.06 ) 61.5 °C.
1H-NMR (300 MHz, CDCl3, ppm) δ: 3.11(2 H, t, J ) 6 Hz),
3.85 (2 H, broad m), 5.99 (1 H, d, J ) 9 Hz), 6.17 (1 H, J ) 9
Hz). 13C-NMR (CDCl3, ppm) δ: 33 (t), 35.7 (t), 119.1 (d), 126.6
(d). IR (neat): 3020, 2920, 1530, 790 cm-1. UV (EtOH): λmax
) 263 nm (ꢀ ) 2500), 321 nm (ꢀ ) 2700). MS (EI/70 eV) m/ z:
150 (M, 69),122, 105 (100), 58, 45 (100).
6,7-Dih yd r o-1,2,5-tr ith iep in (7) via Ch lor in a tion /De-
h yd r och lor in a tion . Recrystallized NCS (16.3 g, 0.12 mol)
was added in small portions to a stirred solution of 1,2,5-
trithiepane (8) (15.4 g, 0.1 mol) in 300 mL of distilled
anhydrous CCl4 at 0 °C over a period of 30 min. Stirring was
continued at 10-15 °C for 3 h. The suspension was cooled,
the succinimide was filtered, and the solution was concentrated
at 18-20 °C under vacuum. The oily residue was dissolved
in 350 mL of anhydrous benzene. To the cooled benzene
solution was added freshly distilled anhydrous triethylamine
(20.2 g, 0.2 mol) dissolved in 50 mL of anhydrous benzene over
a 30 min period. The mixture was subsequently heated at 80
°C for 12 h, cooled, and poured onto 150 mL of ice-cold 3 N
HCl. The layers were separated, and the aqueous layer was
extracted with 100 mL of benzene. The organic layer was
washed with 100 mL of saturated NaCl solution and 100 mL
of a saturated NaHCO3 solution, dried over anhydrous MgSO4,
and evaporated, and the residue was distilled. The yield of
distilled 3,4-dihydro-1,2,5-trithiepin (7) was 2.59 g (17%, bp0.06
) 61-62 °C).
1,2,5-Tr ith iep in (1). A solution of m-CPBA (1.81 g, 10.5
mmol) in 30 mL of CHCl3 was added dropwise to a stirred
solution of 6,7-dihydro-1,2,5-trithiepane (7) (1.5 g, 10 mmole)
in 10 mL of CHCl3 under argon. The temperature of the
reaction was maintained between 0 and 4 °C. Stirring was
continued at this temperature for 1 h. The reaction mixture
was evaporated under vacuum, and 30 mL of freshly distilled
acetic anhydride was added. The reaction flask was placed
in an oil bath preheated to 120 °C and kept at this temperature
under argon for 30 min. The dark reaction mixture was
poured onto 100 mL of ice/water containing some pieces of dry
On the basis of these data it could be classified as a
nonaromatic sulfur heterocycle.
Noteworthy is the observation that while 6,7-dihydro-
1,2,5-trithiepin (7) is perfectly stable over many years
in the cold, the 1,2,5-trithiepin (1) is rather unstable,
rapidly decomposing (polymerizing) neat as well as in
solutions. The reduced thermal stability of 1,2,5-trithi-
epin (1) compared to its dihydro derivative 7 might be
attributed to a more planar geometry of 1 as suggested
from Dreiding models. The planarization of the molecule
leading to a cyclic conjugated 10π-electron-system might
result in a strong splitting of the nonbonding in-plane
orbitals of the disulfide unit in 1, thus generating a high
energy HOMO with a narrow HOMO/LUMO gap.29
Similar arguments have been presented in order to
explain the instability of thioctic acid compared to its six-
and seven-membered analogs. Further studies on the
chemistry of this interesting system, 1,2,5-trithiepin (1)
will be reported.
Exp er im en ta l Section
Gen er a l Com m en ts. Proton and carbon NMR spectra
were measured in CDCl3 at 300 MHz. The variable-temper-
ature data were obtained at 400 MHz. HMQC and HMBC
experiments were performed at room temperature at 500 MHz.
GC-MS were measured at 70 eV under electron impact
conditions. All solvents and reagents were purified prior to
use according to established procedures. Analytical thin layer
chromatography (TLC) was conducted on “Polygram” Sil
G/UV254 plates (0.25 mm). Flash chromatography was per-
formed using Merck silica gel 60 (230-400 mesh).
1,2,5-Tr it h iep a n e 5-S-Oxid e (8): (a ) Wit h m -Ch lor o-
p er ben zoic Acid . A solution of 5.70 g of m-CPBA (33 mmol)
in 30 mL of CHCl3 was added dropwise to a stirred solution of
4.56 g of 1,2,5-trithiepane (6)14 (30 mmol) in 80 mL of CHCl3.
The temperature of the reaction was kept between 0 and 4
°C. Stirring was continued at this temperature for 2 h. The
(27) Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees,
C. W., Eds.; Pergamon Press: Oxford, New York, Toronto, 1984; Vol.
4, Part 3, 3.01.4.1 Table 7.
(28) However, a definite chemical shift assignment is not given.
(29) (a) Steudel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 655 and
references therein. (b) Affleck, J . G.; Dougherty, G. J . Org. Chem. 1950,
16, 865.

2436 J . Org. Chem., Vol. 62, No. 8, 1997
Ueng et al.
ice. After being stirred for 1 h, the mixture was extracted with
ether (2 × 75 mL). The ether layer was neutralized with
saturated ice-cold NaHCO3 solution, washed with saturated
NaCl solution, and dried over anhydrous MgSO4. The crude
material was chromatographed under argon with hexane on
a cooled preparative plate (EM SiO2) yielding a yellow band
of 1,2,5-trithiepin (1). Concentration gave 90 mg of an
unstable yellow oil (6.1%). The compound is stable in dilute
solution in the refrigerator but decomposes rapidly at room
temperature neat or in solution to insoluble probably polymeric
materials.
1. 1H-NMR (CDCl3, ppm) δ: 7.24, 6.57 (AA′XX′, J AX ) 9
Hz). 13C-NMR (CDCl3, ppm) δ: 128.6, 131.5. IR (CCl4): 3100,
1560, 1290, 805, 825 cm-1
. UV (ethanol) λmax: 263 nm (ꢀ )
2250), 296 (1720), 353 (1400). MS (EI/70 eV) m/ z: 148 (30),
116 (29, M - 32), 103 (100, M - 45), 84 (46, M - 64), 64 (15,
M - 84), 58 (92, M - 90), 57 (49, M - 91), 45 (86, M - 103).
HR-MS m/ z: 147.9474 (calcd for C4H4S3 ) 147.947 52).
J O9519625