A novel thiopyran-4-thione synthesis and crystal structure of a thiopyran-4-thione

Article abstract of DOI:10.1039/a908068f

The zinc(n) chloride catalysed reaction between ethylene trithiocarbonate (1) and dibenzoylacetylene (3) gave the novel 2,3,5,6-tetrabenzoylthiopyran-4-thione (4a) and its structure was elucidated by X-ray crystallography. Treatment of 2,3,5,6-tetrabenzoy

Full text of DOI:10.1039/a908068f

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A novel thiopyran-4-thione synthesis and crystal structure of
a thiopyran-4-thione
Jan Oskar Jeppesen,a Niels Thorupb and Jan Becher*a
1
a Department of Chemistry, Odense University (University of Southern Denmark),
Campusvej 55, DK-5230, Odense M, Denmark
b Department of Chemistry, Technical University of Denmark, Building 207, DK-2800 Lyngby,
Denmark
Received (in Cambridge, UK) 7th October 1999, Accepted 29th February 2000
Published on the Web 6th April 2000
The zinc() chloride catalysed reaction between ethylene trithiocarbonate (1) and dibenzoylacetylene (3) gave
the novel 2,3,5,6-tetrabenzoylthiopyran-4-thione (4a) and its structure was elucidated by X-ray crystallography.
Treatment of 2,3,5,6-tetrabenzoylthiopyran-4-chalcogenones (4a,b) with triethyl phosphite afforded the bis-annelated
furans 1,3,5,7-tetraphenylthiopyrano[2,3-c:5,6-cЈ]difuran-8-chalcogenones (5a,b) in almost quantitative yields. The
mechanism for this furan formation is discussed.
Refluxing a catalytic amount of zinc() chloride and a 1:1
mixture of ethylene trithiocarbonate (1) and dibenzoylacet-
ylene (3) in toluene for 18 h gave a different result. Work-up
Introduction
Several alkynes having electron-withdrawing groups react
smoothly with ethylene trithiocarbonate (1) to give substituted
by column chromatography afforded the novel 2,3,5,6-tetra-
1,3-dithiole-2-thiones 2 in good to moderate yields (Scheme 1).1
benzoylthiopyran-4-thione (4a) as a green solid (Scheme 2).6 †
Scheme 2
1H NMR, 13C NMR, high resolution mass spectrometry and
microanalysis all supported the proposed structure 4a. Further-
more, the structure of the thiopyran-4-thione product was
unequivocally determined by single crystal X-ray structure
analysis. Single crystals (green needles) of 4a were obtained
by slow evaporation of an acetone solution of 4a. Fig. 1 shows
Scheme 1
the molecular structure of 4a. The molecule has an apparent
inversion center in the crystal structure. Thus each molecule
appears to be superimposed by its inverted counterpart,
although the inversion center is not dictated by crystal sym-
metry. An explanation might be that during crystallisation each
molecule adopts one of two orientations (thione up or down)
which, however, has little effect on the conformation of the
benzoyl groups and the packing of the molecules. This disorder
was modeled by having S1, S2 and C33 partly (50%) allocated
to their inversion-related positions S1A, S2A and C33A, which
led to a satisfactory refinement of the structure when the
disordered parts were restrained to be almost identical. There-
fore, the calculated distances and angles involving these atoms
should be interpreted with caution. Apparent highly aniso-
tropic displacements of O2 and O4 were modeled by split atom
positions for these atoms (50/50%). No other crystal structure
of a thiopyran-4-thione has been reported in the Cambridge
Crystallographic Database.7
The reaction proceeds as a cycloaddition between the alkyne
and ethylene trithiocarbonate (1) resulting in ethylene evolu-
tion. However, acetylene (case 2f) reacts only under forcing
conditions, and ethylene trithiocarbonate (1) does not react
with methyl-, phenyl- or diphenylacetylenes.1b The scope of the
reaction appears to be limited to alkynes containing electron-
withdrawing substituents.
We present here the first synthesis of a thiopyran-4-thione
derivative from ethylene trithiocarbonate (1) and an alkyne
together with the first crystal structure of a thiopyran-4-
thione.2 The trialkyl phosphite assisted cyclisation of 1,4-
dioxoalkenes to furans has, to our knowledge, only been spor-
adically described in the literature.3 During this work we found
that the method works well for 2,3,5,6-tetrabenzoylthiopyran-
4-chalcogenones.
Results and discussion
The optimum yield of 4a was obtained by using a 1:1 mix-
ture of ethylene trithiocarbonate (1), dibenzoylacetylene (3)
From the results depicted in Scheme 1 it would have been
expected that dibenzoylacetylene (3)4 would react with ethylene
trithiocarbonate (1) to give 4,5-dibenzoyl-1,3-dithiole-2-thione.
Although several attempts were made and different solvents
were tried, we never succeeded in obtaining 4,5-dibenzoyl-1,3-
dithiole-2-thione by this route.5
† Employing a 1:2 mixture of 1 and 3 did not increase the yield of 4a.
It was unfortunately not possible to characterise any other products
unambiguously from the reaction mixture.
DOI: 10.1039/a908068f
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This journal is © The Royal Society of Chemistry 2000
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Transchalcogenation of thione 4a using mercuric acetate in a
mixture of chloroform and glacial acetic acid gave the corre-
sponding ketone 4b as a colourless solid in quantitative yield
(Scheme 4).10 Treatment of 4a,b with triethyl phosphite fol-
lowed by addition of methanol to the reaction mixture and
filtration afforded the bis-annelated furans 5a,b in almost
quantitative yields as orange and brown solids, respectively
(Scheme 4). Elemental analyses and spectral data for com-
pounds 5a,b were all consistent with the assigned structures.
Fig. 1 Molecular structure of 4a. S1A, S2A, C33A, O2A and O4A are
alternate positions for S1, S2, C33, O2 and O4, cf. discussion of dis-
order in text.
and 15 mol% zinc() chloride. Employing 100 mol% zinc()
chloride did not increase the yield of 4a, hence zinc() chloride
probably acts as a catalyst for the reaction. A possible route for
the formation of 4a from 1 and 3, shown in Scheme 3, involves
a 1,3-dipolar cycloaddition of ethylene trithiocarbonate (1) on
dibenzoylacetylene (3) to give the intermediate IA↔IB. For the
alkynes shown in Scheme 1 this type of intermediate loses
ethylene to give 1,3-dithiole-2-thiones. Instead, IB rearranges to
the spiro-thiete compound II facilitated by the positively
charged sulfur atom and coordination of zinc() to a carbonyl
group and a sulfur atom, which makes the olefinic carbon next
to the positively charged sulfur extremely electrophilic. Conver-
sion of II to the vinylog 1,3-dithiolane-2-thione III,8 followed
by a [4 ϩ 2] cycloaddition of III and dibenzoylacetylene gives
the dithioketal IV.9 Using plasma desorption mass spec-
trometry a species with m/z 604 was detected in the reaction
mixture, which could be assigned to the dithioketal IV. Finally,
IV looses thiirane to give the dipolar form 4a(ii) of 4a.‡
Scheme 4
The difference between the thiopyran-4-thione 4a and the
thiopyran-4-one 4b is easily seen from their IR spectra. In both
spectra a broad absorption band (ν = 1668 cmϪ1 in 4a and
ν = 1669 cmϪ1 in 4b) is seen emanating from the carbonyl
stretching mode in the benzoyl groups, but in the spectrum of
4b an additional carbonyl stretching band (ν = 1609 cmϪ1) from
the thiopyran-4-one nucleus is observed.§ In the IR spectra of
5a,b the broad benzoyl carbonyl absorption band is absent. The
carbonyl absorption band from the thiopyran-4-one nucleus in
5b is shifted (45 cmϪ1) towards a higher frequency (ν = 1654
cmϪ1) compared to the carbonyl absorption band in the
thiopyran-4-one nucleus of 4b, indicating that the carbon–
oxygen bond in the thiopyran-4-one nucleus of 5b has more
double bond character as compared to its counterpart in 4b.
‡ Refluxing a 1:1 mixture of ethylene trithiocarbonate (1) and dimethyl
acetylenedicarboxylate and 15 mol% zinc() chloride in toluene
afforded exclusively 4,5-bis(methoxycarbonyl)-1,3-dithiole-2-thione
(2b). It is not fully understood why these reagents exclusively give 2b. An
explanation could be the fundamental difference in reactivity between
an ester group and a keto group together with competition between the
different reaction pathways.
§ In the parent thiopyran-4-one the carbonyl stretching band is
observed at 1609 cmϪ1 (br) (ref. 11). The lack of any absorption band in
the 1660 cmϪ1 region, which would be expected for a conjugated car-
bonyl group, indicates that the thiopyran-4-one nucleus is a resonance
hybrid containing small or no contributions from forms with a carbon–
oxygen double bond (ref. 11).
Scheme 3
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Finally, a carbonyl absorption band is absent from the IR spec-
trum of 5a, which is consistent with the assigned structure.
Conversion of 4a,b to 5a,b, by treatment with triethyl phos-
phite, is formally a reduction. A likely reaction mechanism for
the formation of 4a,b from 5a,b is shown in Scheme 5. The first
were determined on a Büchi melting point apparatus and
are uncorrected. 1H NMR spectra were recorded on a
Gemini-300BB instrument at 300 MHz, using the deuterated
solvent as lock and TMS or the residual solvent as internal
standard. J values are given in Hz. 13C NMR spectra were
recorded at 75 MHz using broad band decoupling. Electron
impact ionisation mass spectrometry (EIMS) was performed on
a Varian MAT 311A instrument. Infrared (IR) spectra were
recorded on a Perkin-Elmer 580 spectrophotometer. Micro-
analyses were performed at the Atlantic Microlab, inc., Atlanta,
Georgia.
2,3,5,6-Tetrabenzoylthiopyran-4-thione 4a
Ethylene trithiocarbonate (1) (1.36 g, 10.0 mmol) was dissolved
in toluene (40 mL) whereupon the yellow solution was purged
with nitrogen (10 min) before dibenzoylacetylene (3)2 (2.34 g,
10.0 mmol) and anhydrous zinc() chloride (0.20 g, 1.5 mmol)
were added. The mixture was refluxed for 18 h causing a slow
colour change to dark green. After cooling to room temp.,
the solvent was removed in vacuo and the dark green oil was
purified by column chromatography on silica using dichloro-
methane–cyclohexane (4:1) as eluent. The dark green band (Rf
0.3) was collected and concentrated to give the thiopyran-4-
thione 4a (0.89 g, 33%) as an analytically pure green solid;
recrystallisation from toluene–cyclohexane gave 4a (0.68 g,
25%) as green needles; mp 233.5–234 ЊC (Found: C, 72.89;
H, 3.63; S, 11.70. C33H20O4S2 requires C, 72.78; H, 3.70; S,
11.77%); νmax(KBr)/cmϪ1 3060w, 1668s (br, PhCO), 1595s,
1580m, 1536m, 1449m, 1340w, 1316m, 1245s (br) and 1179m;
δH (CDCl3) 7.41 (4 H, t, J 7.5), 7.46 (4 H, t, J 7.6), 7.54 (2 H, t,
J 7.3), 7.62 (2 H, t, J 7.4), 7.84 (4 H, d, J 7.4) and 7.89 (4 H, d,
J 7.4 Hz); δC (CDCl3) 128.75, 128.98, 129.09, 130.52, 133.86,
134.18, 135.36, 135.63 (Ar C), 138.14, 150.95 (C᎐C), 189.74,
᎐
192.65 (C᎐O) and 219.78 (C᎐S); m/z (EI) 544 (Mϩ, 42%), 411
᎐
᎐
Scheme 5
(17), 105 (100, PhCOϩ) and 77 (65) (Found: Mϩ, 544.0800.
C33H20O4S2 requires M, 544.0803).
step is a nucleophilic attack of triethyl phosphite at the C-2
position in the thiopyran-4-chalcogenone in a Michael fashion.¶
In the next step the five-membered ring is formed by attack
of the partly negatively (by delocalization) charged oxygen
atom on a neighbouring electrophilic benzoyl group giving
a Wittig related intermediate. This betaine finally loses
triethyl phosphate to give the aromatic furan ring. The driving
force for this reaction is obviously the formation of two aro-
matic furan systems together with the formation of triethyl
phosphate.
Preparation of single crystals for X-ray analysis
Recrystallised 4a (~5 mg) was dissolved in acetone (ca. 2 mL)
and filtered through a folded filter paper in such a way that the
filtrate directly went into a test tube (bore ca. 1 cm). The test
tube was sealed with a septum, which was punctured with
a short disposable needle, and allowed to stand in the dark.
During one week green needles started to grow from the side
and the bottom of the test tube.
Conclusion
2,3,5,6-Tetrabenzoylthiopyran-4-one 4b
In conclusion, novel thiopyran-4-chalcogenones have been
synthesised and characterised. The zinc() chloride catalysed
formation of thiopyran-4-thiones from ethylene trithiocarb-
onate and alkynes have not previously been reported in the
literature and further investigations of this new type of reaction
are currently in progress. The unknown fused difurothiopyran-
4-chalcogenones 5a,b have been synthesised in high yields.
Mercuric acetate (0.80 g, 2.51 mmol) was added in one portion
to a solution of 4a (0.55 g, 1.01 mmol) in a mixture of chloro-
form (30 mL) and glacial acetic acid (3 mL) causing the initially
green solution to change to white within 1 min. The resulting
white suspension was stirred for 1 h at room temp., whereupon
the white precipitate was filtered using Celite (1.0 cm) and
washed thoroughly with dichloromethane (4 × 40 mL). The
combined organic phase was washed with saturated aqueous
sodium hydrogen carbonate (3 × 150 mL), water (2 × 150 mL)
and dried over anhydrous magnesium sulfate. Evaporation of
the solvent in vacuo afforded the thiopyran-4-one 4b (0.53 g,
quantitative) as an analytically pure off-white solid; mp 253–
253.5 ЊC (from toluene–cyclohexane) (Found: C, 75.12; H, 3.90;
S, 6.00. C33H20O5S requires C, 74.99; H, 3.87; S, 6.07%);
νmax(KBr)/cmϪ1 3061w, 1669s (br, PhCO), 1609s (br, CO in
thiopyran unit), 1596s, 1580m, 1531w, 1449m, 1342m, 1315m,
1244s (br) and 1179w; δH (CDCl3) 7.37–7.45 (8 H, m), 7.54 (2 H,
t, J 7.4), 7.60 (2 H, t, J 7.4), 7.77 (4 H, d, J 7.3), 7.86 (4 H, d,
J 7.3); δC (CDCl3) 128.60, 128.88, 129.22, 130.32, 134.00,
Experimental
All reactions were carried out under an atmosphere of dry
nitrogen. Toluene was distilled from sodium–benzophenone.
All reagents were standard grade and used as received unless
otherwise stated. Analytical thin layer chromatography (TLC)
was performed on Merck DC-Alufolien Kieselgel 60 F254 0.2
mm thickness precoated TLC plates, while column chrom-
atography was performed using Merck Kieselgel 60 (0.040–
0.063 mm, 230–400 mesh AST0000M). Melting points (mp)
134.05, 135.22, 135.90 (Ar C), 142.00, 149.27 (C᎐C), 176.82,
᎐
¶ The C-2 position in thiopyran-4-chalcogenones is normally the site of
reaction with nucleophilies (ref. 2b).
189.12 and 192.34 (C᎐O); m/z (EI) 528 (Mϩ, 61%), 395 (18),
᎐
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105 (100, PhCOϩ) and 77 (57) (Found: Mϩ, 528.1012.
C33H20O5S requires M, 528.1031).
Acknowledgements
We thank Odense University for a PhD scholarship to J. O. J.
and Professor M. R. Bryce, University of Durham, for helpful
discussions.
1,3,5,7-Tetraphenylthiopyrano[2,3-c:5,6-cЈ]difuran-8-thione 5a
Compound 4a (0.27 g, 0.50 mmol) was suspended in distilled
triethyl phosphite (20 mL) and heated to 80 ЊC giving a brown
precipitate. The brown suspension was stirred for 1 h at 80 ЊC,
cooled to room temp., and addition of methanol (50 mL)
yielded a brown solid which was filtered and washed with
methanol (2 × 25 mL) to give the thiopyran-8-thione 5a (0.24 g,
94%) as an analytically pure brown solid; mp >265 ЊC (Found:
C, 77.44; H, 3.78; S, 12.54. C33H20O2S2 requires C, 77.32; H,
3.93; S, 12.51%); νmax(KBr)/cmϪ1 3058w, 1603m, 1583w, 1556m,
1531m, 1489m, 1476s, 1444m, 1382m, 1364w, 1178w, 1134m; δH
(CDCl3) 7.33–7.55 (12 H, m) and 7.83–7.87 (8 H, m); m/z (EI)
512 (Mϩ, 66%), 511 (Mϩ Ϫ H, 100), 256 (17), 105 (17, PhCOϩ)
and 77 (23) (Found: Mϩ Ϫ H, 511.0849. C33H19O2S2 requires
M Ϫ H, 511.0827).
References
1 (a) D. B. J. Easton and D. Leaver, J. Chem. Soc., Chem. Commun.,
1965, 22, 585; (b) B. R. O’Connor and F. N. Jones, J. Org. Chem.,
1970, 35, 2002; (c) M. Salle, A. Gorgues, M. Jubault, K. Boubekeur
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2 For comprehensive reviews on thiopyrans, see: (a) A. H. Ingall,
Comprehensive Heterocyclic Chemistry, ed. A. R. Katritzky and
C. W. Rees, Pergamon Press, Oxford, 1984, vol. 3, p. 885; (b) A. H.
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3 (a) F. Ramirez, O. P. Madan and C. P. Smith, J. Org. Chem., 1965,
30, 2284; (b) M. J. Haddadin, B. J. Agha and R. F. Tabri, J. Org.
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J. Chem. Soc., Perkin Trans. 1, 1997, 11, 1617.
1,3,5,7-Tetraphenylthiopyrano[2,3-c:5,6-cЈ]difuran-8-one 5b
4 Dibenzoylacetylene (3) was prepared according to the literature, see:
J. J. Zhang and G. B. Schuster, J. Am. Chem. Soc., 1989, 111, 7149.
5 It has been noted previously that the reaction between 1 and 3 failed
to give 4,5-dibenzoyl-1,3-dithiole-2-thione, see: M. Ahmed, J. M.
Buchshriber and D. M. McKinnon, Can. J. Chem., 1970, 48, 1991.
6 The unexpected formation of thiopyran-4-chalcogenone derivatives
has been observed previously and was explained by the stability of
the thiopyran-4-chalcogenone systems, see: C. J. Grol, Tetrahedron,
1974, 30, 3621.
7 Crystal structures of thiopyran-4-ones have been reported, see for
example: (a) C. H. Chen, G. A. Reynolds, D. L. Smith and J. L. Fox,
J. Org. Chem., 1984, 49, 5136; (b) A. Banerjee, C. J. Brown and P. C.
Jain, Acta Crystallogr., Sect. A, 1985, 41, 1505; (c) M. Hemmerling,
S. Hunig, M. Kemmer and K. Peters, Eur. J. Org. Chem., 1998, 1989.
8 This kind of equilibrium has been described in the literature, see for
example; J. D. Coyle, P. A. Rapley, J. Kamphuis and H. J. T. Bos,
J. Chem. Soc., Perkin Trans. 1, 1986, 2173.
Compound 4b (0.53 g, 1.00 mmol) was suspended in distilled
triethyl phosphite (40 mL) under nitrogen and heated to 80 ЊC
giving an orange precipitate. The orange suspension was stirred
for 1 h at 80 ЊC, cooled to room temp., and addition of methanol
(100 mL) yielded an orange solid which was filtered and washed
with methanol (2 × 50 mL) to give the thiopyran-8-one 5b (0.46
g, 93%) as analytically pure orange needles; mp > 265 ЊC
(Found: C, 79.54; H, 4.01; S, 6.53. C33H20O3S requires C, 79.82;
H, 4.06; S, 6.46%); νmax(KBr)/cmϪ1 3060w, 1654s (CO in
thiopyran unit), 1602m, 1577m, 1557s, 1491m, 1479s, 1444m,
1374w; δH (CDCl3) 7.36–7.58 (12 H, m), 7.89 (4 H, dd, J 8.5 and
1.1) and 8.26 (4 H, dd, J 8.0 and 1.6); m/z (EI) 496 (Mϩ, 100%),
391 (8), 248 (25), 145 (55), 105 (73, PhCOϩ) and 77 (61) (Found:
Mϩ, 496.1125. C33H20O3S requires M, 496.1132).
9 A number of similar [4 ϩ 2] cycloadditions of related structures of
III and alkynes, to give spiro-thiopyrans (related to IV) have been
reported, see for example: (a) E. Fanghänel, T. Palmer, J. Kersten,
R. Ludwigs, K. Peters and H. G. Schnering, Synthesis, 1994, 1067;
(b) R. Okazaki, K. Sunagawa, K.-T. Kang and N. Inamoto, Bull.
Chem. Soc. Jpn., 1979, 52, 496; (c) D. B. J. Easton, D. Leaver and
T. J. Rawlings, J. Chem. Soc., Perkin Trans. 1, 1972, 41.
10 To our knowledge transchalcogenation of thiopyran-4-thiones using
mercuric acetate in chloroform and glacial acetic acid have
apparently not been reported, although this method has been widely
used for transchalcogenation of 1,3-dithiole-2-thiones to the
corresponding 1,3-dithiole-2-ones, see: N. Svenstrup and J. Becher,
Synthesis, 1995, 215.
11 D. S. Tarbell and P. Hoffman, J. Am. Chem. Soc., 1954, 76, 2451.
12 (a) G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467; (b)
G. M. Sheldrick, SHELXL-97, Program for the Refinement
of Crystal Structures, University of Göttingen, Germany, 1997; (c)
A. L. Spek, Acta Crystallogr., Sect. A, 1990, 46, C-34; (d) G. M.
Sheldrick, SHELXTL, Structure Determination Programs, Version
5.10, Bruker (formerly Siemens) Analytical X-Ray Instruments Inc.,
Madison, Wisconsin, USA, 1997.
Crystallographic data for compound 4a||
C33H20O4S2, M = 544.63, orthorhombic, a = 21.094(2), b =
5.6478(6), c = 21.496(2) Å, V = 2561.0(4) Å3, space group Pca21
(No. 29), Z = 4, Dx = 1.413 g cmϪ3, F(000) = 1128, graphite
monochromated Mo-Kα radiation, λ = 0.71073 Å, µ = 0.248
mmϪ1, T = 120 K. Crystal size: 0.48 × 0.23 × 0.11 mm, green
needles. The intensities of 25516 reflections were measured on a
Siemens SMART CCD diffractometer to θmax = 26.40Њ, and
were merged to 5235 unique reflections (Rint = 0.028). Structure
solution, refinement and analysis of the structure, and produc-
tion of crystallographic illustrations were carried out using the
programs SHELXS97,12a SHELXL97,12b PLATON12c and
SHELXTL.12d The refinement using 381 parameters converged
at R1 = 0.0362 (for Fo > 4σ(Fo)).
|| CCDCreferencenumber207/404. Seehttp://www.rsc.org/suppdata/p1/
a9/a908068f for crystallographic files in .cif format.
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J. Chem. Soc., Perkin Trans. 1, 2000, 1467–1470