Thiocarbonyl polyenes: Monomers, trimers and thiopyrans

Article abstract of DOI:10.1016/j.tetlet.2012.10.012

Polyunsaturated conjugated thiocarbonyl compounds (thioxocarotenoids) occur as monomers or react instantaneously to give polyene substituted trithiacyclohexanes and 2H-thiopyrans.

Full text of DOI:10.1016/j.tetlet.2012.10.012

Tetrahedron Letters 53 (2012) 6822–6825
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Thiocarbonyl polyenes: monomers, trimers, and thiopyrans
Eugenia M. Sandru, Jan Sielk, Jens Burghaus, Christer L. Øpstad, Nebojsa Simic, Susana Villa Gonzales,
⇑
Hans-Richard Sliwka , Vassilia Partali
Department of Chemistry, Norwegian University of Science and Technology, 7491 Trondheim, Norway
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 July 2012
Revised 22 September 2012
Accepted 4 October 2012
Available online 12 October 2012
Polyunsaturated conjugated thiocarbonyl compounds (thioxocarotenoids) occur as monomers or react
instantaneously to give polyene substituted trithiacyclohexanes and 2H-thiopyrans.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Cyclization
Polyene
Thiacyclohexane
Thiones
Thioaldehydes
2H-Thiopyran
The preparation of self-assembled monolayers (SAMs) is associ-
ated with the reaction of Au surfaces with saturated thiols, thiocy-
anates, thioesters, thiosulfates, acyclic disulfides, or thiiranes.1 The
SAM is formed via a thiolate–Au bond by expelling residual atoms
at S (H, CN, CH3C@O, SO3, and SR) or by breaking the thiirane struc-
ture. Molecular wire studies require unsaturated SAMs. Polyunsat-
urated SAMs connected by conjugation via sulfur to Au cannot
evolve like saturated SAMs because of instability problems with
alkenethiols or thiirenes. Consequently, polyene SAMs were previ-
ously connected to gold via an insulating methylene group
(Fig. 1a).2,3 We have found that a long chain unsaturated thioke-
tone assembled via a conjugated polyenolate bonding on Au
(Fig. 1b).4
Long chain unsaturated aldehydes and ketones are daily di-
gested in the diet as natural ingredients or as added food colors,
for example, C30 aldehyde 1 E160e, rhodoxanthin (5) E161f, can-
thaxanthin (10) E161 g, astaxanthin (14) E161j, and citranaxanthin
(18) E161i (Schemes 1–3 and 5). How do these food colors behave
when associated with sulfur? Carotenoids in the presence of sul-
fur-containing compounds display an often desired color deepen-
ing.5 On the other hand, the occurrence of sulfides accelerates
the photodegradation of carotenoids.6,7 Nonetheless, it was veri-
fied that VIS and CD spectra, and, hence, the stability of caroten-
ethiols, were not affected by the –SH group.2,8–10 While the
characteristic color (mostly red or violet with low intensity
strength) of saturated thiones can be durable (e.g., thioacetone),11
the unsaturated counterparts bear the stigma of ‘too reactive even
at low temperature’.12 For certain, simple thials are unstable,
whether they are saturated or unsaturated, cyclic or acyclic; they
all trimerize immediately to thiacyclohexanes (1,3,5-trithi-
anes),13–19 or, rarely, they dimerize to dithianes or dithiacyclobu-
tanes (1,3-dithietanes).20,21 In contrast, the outcome of
a
thioketone synthesis is not always predictable. Acyclic thiones
are stable or unstable, they may dimerize or trimerize;14,22,23 cyclic
thiones are stable, including
a,b-unsaturated cyclohexenethiones,
or unstable.12 The present study was undertaken with the aim of
extending our previous investigations with thioxopolyenes.
When C30-aldehyde 1 was reacted with Lawesson’s reagent 2,24
the orange toluene solution changed to yellow (Fig. S1 in the Sup-
plementary data). The absence of the C@O band in a IR spectrum
together with NMR and MS data suggested instant trimerization
of intermediate C30-thioaldehyde 3 to propeller-shaped trithiane
4 in the preferred eq,eq,eq-conformation25,26 [(29:3)3-trithiane,
(29:3)3-6S3 in crown ether nomenclature (Scheme 1 and Fig. 2).27
Figure 1. (a) Polyene connected to Au via an ‘insulator to metal’ arrangement,2 (b)
⇑
Corresponding author. Tel.: +47 73595600; fax: +47 73596255.
E-mail address: hrs@nvg.ntnu.no (H.-R. Sliwka).
polyene connected to Au via a conjugated enethiolate bond.4
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.012

E. M. Sandru et al. / Tetrahedron Letters 53 (2012) 6822–6825
6823
Scheme 1.
The reaction of 1 to trithiane 4 via transient thioaldehyde 3 is in
line with observations on retinethial and other intermediate thi-
oaldehydes.13,28 We suppose that other carotenals like C30-alde-
hyde 1 would similarly react to trithianes.29
Trithianes react with Ag and Au salts to give complexes with the
intact ring; the ring is also integrally adsorbed on Ag surfaces.30–32
It is probable that trithiane 4 similarly assembles on Ag or Au sur-
faces without ring dissociation. Thus, the anticipated solidity of
polyenyl trithianes would prevent the formation of nonstop conju-
gated monolayers on Au. Retinethial not only trimerized to the re-
lated trithiane but also formed at lower temperature polyene
substituted 4-methyl-2H-thiopyran.28,33
Scheme 2.
by S. In addition to 1D 1H and 13C NMR spectra, the structure of 17
was established by HSQC, COSY, and HMBC spectra, leaving
initially just one doubt—the location of one of the two Me groups
on the sulfur ring. A 2D NOESY experiment showed no correlation
between the allocated Me group at C5 (1.36 ppm) with the non-
allocated Me group (1.97). Therefore, the only possible place for
the Me group at 1.97 was C-2. Additional proof was attained by
running the experiments in DMSO-d6, which allowed distinction
between protons H-3 and H-4 (in CDCl3 the shifts coincided). Their
vicinal position was then confirmed by COSY and their relative
arrangement in the molecule by HMBC. Establishing the 5H-thio-
chromene structure 17 corroborated the hitherto just once re-
ported reaction of thione 16.38 The increase in absorption
(25 nm) of thiochromene 17 compared to b-ionone 15 demon-
strates imminent auxochrome properties of the 2H-thiopyran ring
caused by conjugation of the double bonds with the sulfur orbitals
(Figs. S3 and S4 in the Supplementary data).39,40 Such an auxo-
chrome effect has also been observed in 2H-pyran-carotenoids.41
When Lawesson’s reagent 2 was reacted with citranaxanthin
(18), a fading of the color was seen similar to C30-aldehyde 1
(Scheme 5, Fig. S5 in the Supplementary data). The frequently re-
ported trimerization to a trithiane was, therefore, anticipated.
Yet, mass spectroscopy data of the product pointed to the uptake
of only one sulfur atom. The precise assignments of proton and car-
bons, achieved by iterative interpretation of spectra from different
The initial reaction of diketones rhodoxanthin (5) and cantha-
xanthin (10) with Lawesson’s reagent 2 gave monothiones 6 and
11 with a distinct bathochromic shift in the VIS spectra, similar
to the shift of thioechinenone 12 (Schemes 2 and 3).34 Rhodoxan-
thin dithione 7 and canthaxanthin dithione 13 were prepared by
extending the reaction time, carefully controlling product forma-
tion and decomposition (visual evidence). The two thione groups
increased kmax and noticeably decreased the stability of 7 and 13
(Fig. S2 in the Supplementary data). In contrast, a less stable mono-
thione and a more stable dithione were found with the cyclopente-
none carotenoid 20,20-dinor-canthaxantin.35 Fading of the
characteristic thione color to the shade of the starting compound
or to even lighter colors was not observed; therefore, carotenoid
monothiones 6 and 11 did not noticeably tautomerize over time
to labile enethiols36,37 for example 8; nor did they trimerize to tri-
thiane 9 (Scheme 2).21,23 Since canthaxanthin monothione 11 self-
assembled with an enethiolate bond on gold (Fig. 1b)4 it can be
predicted that other cyclohexenethiones29 will react analogously.
Thus, carotenyl cyclohexenethiones are potential candidates for
fully conjugated monolayers on Au. Hydroxyketones such as asta-
xanthin (14) (Scheme 3) failed to form thioketones.
The reaction of sulfur reagent 2 with b-ionone (15) (Scheme 4)
gave a product, whose mass spectra indicated the replacement of O
Figure 2. Structure of eq,eq,eq-trithiane 4 (MMFF/SYBYL, Spartan 08).

6824
E. M. Sandru et al. / Tetrahedron Letters 53 (2012) 6822–6825
HMBC experiment undoubtedly pointed to a 6-membered hetero-
cycle including sulfur.
Intuitively, the trimerization of trans-thione 19a to the corre-
sponding trithiane seems more plausible than cyclization of cis-
thione 19b to 2H-thiopyran, which is not a stable structural unit
when lacking stabilizing substituents.43 Nevertheless, the sponta-
neous cyclization of polyene thiones 16 and 19 to 17 and 20 could
represent pioneering examples of a general approach to 2,6-disub-
stituted 2H-thiopyrans.44 It is probable that not only citranaxan-
thin (18) but also other alkyl-carotenyl ketones29 cyclize to 2H-
thiopyran polyenes. The thiopyran ring lacks an auxochromic influ-
ence in 20 due to conjugation interruption between the polyene
chain and the perpendicularly oriented sulfur ring (Fig. S6).45 An
auxochromic effect is likewise not seen after protonation of 20;
the resulting color change originates merely from the octaenylium
chain, which is not coplanar with the aromatic thiopyrylium chro-
mophore.41,44 If carotenyl 2H-thiopyrans were to assemble by ring
breaking on Au, a conjugated monolayer might result.
In summary, unsaturated aldehyde 1 reacted upon thionation to
give trithiane, in accordance with trithiane formation from satu-
rated aldehydes. Polyene substituted cyclohexenones form thiones.
The polyenyl cyclohexenethiones are processible under normal
conditions at laboratory conditions without special precautions.8
Polyene diones preferentially afforded monothiones; dithiones
decomposed quickly. In contrast to saturated thiones, methyl-
polyenyl thiones cyclized to 2H-thiopyrans. The 1,6-cyclization of
transient polyene thiones to 2H-thiopyrans can be added to the
common spontaneous reactions of thiocarbonyl compounds.
Polyenyl cyclohexenethiones are promising candidates for assem-
bling conjugated monolayers on Au. Whether molecules 17 and
20 self-assemble on gold surfaces with the intact thiacycle or by
dissociative chemisorption is yet to be ascertained.
Scheme 3.
Acknowledgment
Scheme 4.
We thank Dr. H. Ernst, BASF SE, Ludwigshafen, Germany, for a
generous gift of the carotenoids.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
10.012.
References and notes
1. Love, J. C.; Estroff, L. A.; Kriebel, J. K.; Nuzzo, R. G.; Whitesides, G. M. Chem. Rev.
2005, 105, 1103–1169.
2. Leatherman, G.; Durantini, E. N.; Gust, D.; Moore, T. A.; Moore, A. L.; Stone, S.;
Zhou, Z.; Rez, P.; Liu, Y. Z.; Lindsay, S. M. J. Phys. Chem. B 1999, 103, 4006–4010.
3. He, J.; Chen, F.; Li, J.; Sankey, O. F.; Terazono, Y.; Herrero, C.; Gust, D.; Moore, T.
A.; Moore, A. L.; Lindsay, S. M. J. Am. Chem. Soc. 2005, 127, 1384–1385.
4. Ion, A.; Partali, V.; Sliwka, H. R.; Banica, F. G. Electrochem. Commun. 2002, 4,
674–678.
5. Auweter, H.; Bohn, H.; Horn, D.; Krämer, K.; Weiss, H. BASF SE, DE19831865,
2000; Chem. Abstr. 2000, 132, 92508.
6. Arita, S.; Ando, S.; Hosoda, H.; Sakaue, K.; Nagata, T.; Murata, Y.; Shimoishi, Y.;
Tada, M. Biosci. Biotechnol. Biochem. 2005, 69, 1786–1789.
7. Zhang, G. L.; Zhu, B. W.; Nakamura, Y.; Shimoishi, Y.; Murata, Y. Biosci.
Biotechnol. Biochem. 2008, 72, 2176–2183.
Scheme 5.
8. Sliwka, H. R.; Liaaen-Jensen, S. Acta Chem. Scand. 1990, 44, 61–66.
9. Sliwka, H. R.; Liaan-Jensen, S. Tetrahedron: Asymmetry 1993, 4, 361–368.
10. Sliwka, H. R. Helv. Chim. Acta 1999, 82, 161–169.
11. Lipscomb, R. D.; Sharkey, W. H. J. Polym. Sci. A: Polym. Chem. 1970, 8, 2187–
2196.
NMR techniques, established the formation of 2-carotenyl-3,6-
dimethylthiopyran 20 by 1,6-intramolecular cyclization of inter-
mediate 80-cis-(Z)-thioketone 19b derived from 80-trans-(E) 19a
(Scheme 5). Chemical shifts of protons and carbons in the polyene
chain were in accordance with published NMR data.42 Other shifts,
divergent from the polyene values, indicated the occurrence of an
additional structural moiety in the molecule. Particularly the
12. Briard, E.; Levillain, J.; Ripoll, J. L.; Dat, Y.; Marcual, A.; Lange, C. Eur. J. Org.
Chem. 1999, 869–874.
13. Wagner, A. Houben-Weyl
– Methoden der Organischen Chemie, S-, Se-, Te-
Verbindungen; Thieme: Stuttgart, 1955. pp 699–703.
14. Voss, J. Houben-Weyl – Methoden der Organischen Chemie, Org. S-Verbindungen;
Thieme: Stuttgart, 1985. p 188.

E. M. Sandru et al. / Tetrahedron Letters 53 (2012) 6822–6825
6825
15. Salama, T. A.; El-Ahl, A. A. S.; Elmorsy, S. S.; Khalil, A. G. M.; Ismail, M. A.
Tetrahedron Lett. 2009, 50, 5933–5936.
32. Edema, J. J. H.; Buter, J.; Vanbolhuis, F.; Meetsma, A.; Kellogg, R. M.; Kooijman,
H.; Spek, A. L. Inorg. Chim. Acta 1993, 207, 263–265.
16. Giles, H. G.; Marty, R. A.; Mayo, P. D. J. Chem. Soc., Chem. Commun. 1974, 409–
410.
33. Chechak, A. J.; Robeson, C. D.; Stern, M. H. Eastman Kodak Rochester,
GB945882, 1965; Chem. Abstr. 1967, 66, 2666.
17. Okazaki, R.; Ishii, A.; Fukuda, N.; Oyama, H.; Inamoto, N. J. Chem. Soc., Chem.
Commun. 1982, 1187–1188.
18. Vedejs, E.; Perry, D. A.; Wilde, R. G. J. Am. Chem. Soc. 1986, 108, 2985–2989.
19. Schenk, W. A.; Beucke, T.; Burzlaff, N.; Klüglein, M.; Stemmler, M. Chem. Eur. J.
2006, 12, 4821–4834.
20. Li, J.; Tomfohr, J. K.; Sankey, O. F. Physica E 2003, 19, 133–138.
21. Nishio, T.; Yoshioka, M.; Aoyama, H.; Sugiyama, N. Bull. Chem. Soc. Jpn. 1973, 46,
2253–2254.
22. Mayer, R. In Organosulfur Chemistry; Jansen, M. J., Ed.; Interscience: New York,
1967.
34. Sliwka, H. R.; Liaaen-Jensen, S. Acta Chem. Scand. 1994, 48, 679–683.
35. Hartmann, J. Thesis, Universität Düsseldorf, Germany, 1995, pp 59–60.
36. Allegretti, P. E.; Schiavoni, M. D.; Cortizo, M. S.; Castro, E. A.; Furlong, J. J. P. Int.
J. Mol. Sci. 2004, 5, 294–300.
37. Barton, D. H. R.; Choi, L. S. L.; Hesse, R. H.; Pechet, M. M.; Wilshire, C. J. Chem.
Soc., Perkin Trans. 1 1979, 1166–1175.
38. Fournier, C.; Paquer, D.; Vazeux, M. Bull. Soc. Chim. Fr. 1975, II, 2753–2756.
39. Parasaran, T.; Price, C. C. J. Org. Chem. 1964, 29, 946–947.
40. Jacquemin, D.; Wathelet, V.; Perpète, E. A. J. Phys. Chem. A 2006, 110, 9145–
9152.
23. Usov, V. A.; Timokhina, L. V.; Usova, T. L.; Voronkov, M. G. Zh. Org. Khim. 1981,
17, 1327–1328.
24. Pedersen, B. S.; Scheibye, S.; Nilsson, N. H.; Lawesson, S. O. Bull. Soc. Chim. Belg.
1978, 87, 223–228.
25. Sekido, K.; Itoh, J.; Noguchi, T.; Hirokawa, S. Bull. Chem. Soc. Jpn. 1981, 54, 1881–
1882.
41. Øpstad, C. L.; Sliwka, H. R.; Partali, V. Eur. J. Org. Chem. 2010, 435–439.
42. Englert, G. In Carotenoids Volume 1B: Spectroscopy; Britton, G., Liaaen-Jensen, S.,
Pfander, H., Eds.; Birkhäuser: Basel, 1995. Chapter 6.
43. Weissenfels, M.; Pulst, M.; Greif, D. Sulfur Rep. 1993, 15, 161–233.
44. The thionation reaction is exemplified with citranaxanthin (18): 110-apo-110-
(3,6-dimethyl-2H-thiopyran-2-yl)-b-carotene (20). Lawesson’s reagent
2
26. Campaigne, E.; Chamberlain, N. F.; Edwards, B. E. J. Org. Chem. 1962, 27, 135–
138.
27. Guyon, V.; Guy, A.; Foos, J.; Lemaire, M.; Draye, M. Tetrahedron 1995, 51, 4065–
4074.
28. Chechak, A. J.; Stern, M. H.; Robeson, C. D. J. Org. Chem. 1964, 29, 187–189.
29. Britton, G.; Liaaen-Jensen, S.; Pfander, H.; Mercadante, A. Z.; Egeland, E. S.
Carotenoids Handbook; Birkhäuser: Basel, 2004.
30. Oh, S. T.; Kim, K.; Kim, M. S. J. Mol. Struct. 1991, 243, 307–323.
31. Yue, C. Y.; Chen, W. D.; Jiang, F. L.; Feng, R.; Hong, M. C. Inorg. Chem. Commun.
2010, 13, 105–108.
(70 mg, 0.17 mmol) was dissolved in CS2 at reflux. Citranaxanthin (18,
100 mg, 0.218 mmol) was added and refluxed under N2 for 12 h. The
reaction was monitored by TLC on Al2O3 using hexane:toluene: acetonitrile
72:25:3. The crude product was purified by flash chromatography on Al2O3
with hexane:toluene:acetonitrile 94.3:5:0.7 to afford 65 mg 20 (63%);
kmax = 416 nm (CH2Cl2, Fig. S5 in the Supplementary data). HRMS (EI): Calcd:
472.3164, found: m/z = 472.3152 (M+). The synthesis of other unsaturated and
saturated thioxo compounds is reported in Supplementary data.
45. Weissenfels, M.; Pulst, M.; Greif, D. Phosphorus, Sulfur, Silicon 1991, 58, 311–
324.