Thermal reactions of regioisomeric 1,2,4-trithiolane s-oxides

Article abstract of DOI:10.1002/ejoc.200901440

The products of the gas-phase pyrolysis of two regioisomeric 1,2,4-trithiolane S-oxides were collected in an argon matrix at 1OK and studied by means of spectroscopic as well as computational methods. Whereas the main products of the pyrolysis of the symmetrical S-oxide were identified as thioformaldehyde S-oxide and thioformaldehyde S-sulfide, the non-symmetrical S-oxide gave predominantly dithioformic acid, which exists as a mixture of s-cis and s-trans conformers. We present a rationalization of the reaction pathways including density functional theory computations.

Full text of DOI:10.1002/ejoc.200901440

FULL PAPER
DOI: 10.1002/ejoc.200901440
Thermal Reactions of Regioisomeric 1,2,4-Trithiolane S-Oxides
Grzegorz Mloston,*[a] Jaroslaw Romanski,[a] Michael L. McKee,[b] Hans Peter Reisenauer,[c]
and Peter R. Schreiner*[c]
Keywords: Flash pyrolysis / Matrix isolation / Sulfur heterocycles / Thiocarbonyl compounds / Thiocarbonyl S-oxides
The products of the gas-phase pyrolysis of two regioisomeric
1,2,4-trithiolane S-oxides were collected in an argon matrix
at 10 K and studied by means of spectroscopic as well as
computational methods. Whereas the main products of the
pyrolysis of the “symmetrical” S-oxide were identified as
thioformaldehyde S-oxide and thioformaldehyde S-sulfide,
the “non-symmetrical” S-oxide gave predominantly dithio-
formic acid, which exists as a mixture of s-cis and s-trans
conformers. We present a rationalization of the reaction path-
ways including density functional theory computations.
Introduction
tion of 4a was accompanied by small amounts of dithiirane
(5a) that was detected at 10 K in the matrix-isolated pyroly-
zate. Subsequent irradiation of this mixture led to nearly
complete conversion of 4a into the isomeric 5a
(Scheme 1).[4]
Recent studies on “sulfur-centered” 1,3-dipoles focused on
applying matrix isolation techniques to examine the thio-
carbonyl ylides 1a and 1b[1a] generated in the gas phase by
thermal elimination ([2+3]-cycloreversion) of nitrogen from
the corresponding 2,5-dihydro-1,3,4-thiadiazoles 2a and 2b
(Scheme 1).[1b]
A similar result of a thermal [2+3]-cycloreversion was
obtained in the case of 3,3,5,5-tetramethyl-1,2,4-trithiolane
1,2,4-Trithiolanes 3 are common in nature[2] and there is (3b) but in this case, in addition to the thioacetone S-sulfide
a variety of preparative methods for their synthesis.[2a,2g,2h,3] (4b) and 3,3-dimethyldithiirane (5b) formed as minor prod-
In an earlier study we demonstrated that the gas phase pyr- ucts, the isopropenyl disulfane (6), present as a mixture of
olysis of the parent 1,2,4-trithiolane (3a) yields the thiofor- two conformers, was found as the major component of the
maldehyde S-sulfide (thiosulfine, 4a), which is another rep- frozen pyrolyzate. The latter is believed to form from the
resentative of a “sulfur-centered” 1,3-dipole.[4] The forma- thiosulfine 4b via a 1,4-H shift (Scheme 2).[5]
Scheme 1.
Spirocycloaliphatic 1,2,4-trithiolane 3c was reported to
[a] University of Lodz, Section of Heteroorganic Compounds,
undergo gas phase thermolysis yielding a mixture of thio-
sulfine 4c, the spirocyclic dithiirane 5c, and dithiolactone
7.[5] The five-membered product 7 apparently forms via the
ring enlargement of 5c, which occurred under both thermal
and photolytic conditions.
The mono-oxidation reactions of 1,2,4-trithiolanes 3a,b,d
are well documented and it is known that irrespective of the
oxidizing agent [sodium periodate, m-chloroperbenzoic acid
(mCPBA) or peracetic acid], mixtures of comparable
Tamka 12, 91-403 Lodz, Poland
Fax: +48-42-665-51-62
E-mail: gmloston@uni.lodz.pl
[b] Auburn University, Department of Chemistry and
Biochemistry,
Auburn, AL 36849, USA
[c] Justus-Liebig University, Institute of Organic Chemistry,
Heinrich-Buff-Ring 58, 35392 Giessen, Germany
Fax: +49-0641-99-34209
E-mail: prs@org.chemie.uni-giessen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901440.
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Thermal Reactions of Regioisomeric 1,2,4-Trithiolane S-Oxides
Scheme 2.
amounts of regioisomeric monoxides 8a,b,d and 9a,b,d
We describe in this paper the high-vacuum flash pyrolysis
ensue (Scheme 3).[2c,6] Wratten and Faulkner[2c] showed that (HVFP) products of 4-S-oxide 8a and 1-S-oxide 9a, derived
1,2,4-trithiolane 4-S-oxide (8a) and the isomeric 1-S-oxide from 1,2,4-trithiolane (3a) isolated at low temperature
9a can be isolated from red algae Chondria Californica.[2c] (10 K). Density functional theory (DFT) computations are
After isolation from the biological material, both com- used to rationalize our findings.
pounds were separated by preparative thin layer chromatog-
raphy. Biological tests proved that both S-oxides 8a and 9a
display a remarkable antimicrobial activity.[2c] It is worth
mentioning that propanethial S-oxide (n-propyl sulfine),
known as the “lachrymatory factor” isolated from allium
species has been postulated to form via an enzymatic con-
version of S-propen-1-yl-cystein S-oxide.[7]
Results and Discussion
We utilized the monoxides 8a and 9a, obtained as pure
samples after treatment of the parent 1,2,4-trithiolane (3a)
with mCPBA and chromatographic separation, for the py-
rolysis experiments using an empty quartz tube heated up
to 700 °C. A stream of gaseous products was condensed on
a cold spectroscopic window (CsI or BaF2) together with a
large excess of argon. The matrix-isolated pyrolysis prod-
ucts were examined by IR and UV/Vis spectroscopy.
The first series of pyrolysis experiments was carried out
with the “symmetrical” 4-S-oxide 8a. The IR spectrum of
the pyrolyzate collected at 10 K revealed the presence of
very strong absorption bands at 766.7 and 1165.6 cm–1,
which were attributed to the wagging vibrations of the CH2
group and the S=O strechings in thioformaldehyde S-oxide
(10), respectively (Scheme 4).
Scheme 3.
In contrast to 1,2,4-trithiolanes of type 3, the reactions
of the respective monoxides 8 and 9 are less well known.
Only recently, the reactions of 8a,d and 9a,d (R, R = H, H
or cyclohexylidene) with Pt0-phosphane complexes have
Scheme 4.
These strong bands are accompanied by less intense ab-
been reported.[6b,8] In the case of 1,2,4-trithiolanes and their sorptions at 1153.1 and 1357.2 cm–1 (Figure 1) and fit well
S-oxides, the complexation reactions occur via dissociation with the literature data reported for 10.[9,10] The second
of the heterocyclic ring and result in the release of the corre- main product present in the mixture was identified as thi-
sponding sulfine.
oformaldehyde S-sulfide (4a). Its presence was clearly con-
In a very recent paper, in an attempt to photolyze thio- firmed in the IR spectrum by absorptions found at 622.8,
formaldehyde S-oxide (the parent sulfine, 10) to oxathiirane 756.8, 910.2, and 970.9 cm–1. All of these bands were al-
(in Ar matrix at 10 K), we reported the unexpected forma- ready found and described in our earlier paper reporting on
tion of a very rare product of “methylidyne(hydroxy)sulf- the [2+3] thermal cycloreversion of the parent 1,2,4-trithio-
anyl type” 11, possessing a CS triple bond.[9]
lane (3a) (Scheme 2).[4] Thioformaldehyde (12) was also
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G. Mloston, P. R. Schreiner et al.
FULL PAPER
Figure 1. IR spectrum of matrix-isolated (argon, 10 K) high-vacuum flash pyrolysis products of 1,2,4-trithiolane 4-S-oxide (8a) generated
at 650 °C.
Figure 2. UV/Vis spectrum of matrix-isolated (argon, 10 K) high-vacuum flash pyrolysis products of 1,2,4-trithiolane 4-S-oxide (8a)
generated at 650 °C.
present in the mixture (IR bands located at 987.4 cm–1 and dissociation, the formation of equal amounts of 10 and 4a
1055.2 cm–1). The computed intensities of the CH2-wagging are expected. The presented pathway fits well with the pre-
vibrations of products 10, 4a, and 12 [B3LYP/6- diction resulting from our computational studies, which
311+G(3df,3dp)][11] were used to estimate of the ratio of all give an activation energy of 31 kcalmol–1 (Figure 3).
three compounds. This procedure led to the conclusion that
Apparently, some amount of thiosulfine 4a undergoes
the 10/4a/12 ratio is approximately 2:1:1. Moreover, small decomposition in the gas phase and therefore thioformal-
amounts of S2 also formed as evident from the presence of dehyde 12 as well as disulfur S2 were also detected in the
its characteristic UV-absorptions between 280 and matrix. However, it must be stressed that elimination of S1,
310 nm.[12] In addition, the UV spectrum of a mixture of either from 4a or from 5a, is an endothermic process with
all compounds shows two intense bands at 356 nm (attrib- ∆E ≈ 80 kcalmol–1 [B3LYP/6-311+G(3df,3dp)]. Therefore,
uted to thiosulfine 4a[4]) and at 242 nm (attributed to sulfine the pathway leading to S2 is not clear.
10[9]) (Figure 2).
In addition to our results, an earlier paper describes a
The simultaneous formation of two main products, the similar gas phase pyrolysis study of 8a, and the products
sulfine 10 and thiosulfine 4a, results from the thermal formed at 817 °C were characterized by means of photo-
[2+3]-cycloreversion of the five-membered ring of 8a. Ac- electron spectroscopy.[13] In this case the formation of 10
cording to the presented reaction mechanism of the ring and 12 was shown but the formation of 4a had not been
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Thermal Reactions of Regioisomeric 1,2,4-Trithiolane S-Oxides
present study was relatively low. Therefore, the open form
of the thiosulfine 4a is strongly favored in comparison to
the cyclic product 5a.
The isomeric, “non-symmetrical” 1,2,4-trithiolane 1-S-
oxide (9a) was pyrolyzed under similar conditions and the
products formed in the gas phase were isolated in an argon
matrix and studied by means of their IR and UV spectra.
The IR spectrum of the pyrolysis products taken at 10 K
showed intense bands attributed to 10 and another group
of bands, which revealed the presence of a mixture of s-cis
(1290.3, 1058.0, 933.5, 826.5, 682.8 cm–1) and s-trans
(1265.1, 1082.1, 925.4, 806.5, 725.9 cm–1) dithioformic acid
(13c and 13t) as the major components of this mixture
(Scheme 5).[14] These absorptions fit well with those found
in the photolysis products of 4a.[4] Along with 10 and 13, a
small amount of 12 was also found in the mixture. Based
on a comparison of the intensities of the corresponding
bands, the 10/12 ratio was estimated to be ca. 10:1 (Fig-
ure 4).
Figure 3. Reaction profile (kcalmol–1) for the [2+3] cycloreversion
of 1,2,4-trithiolane 4-S-oxide (8a) at the B3LYP/6-311+G(3df,3pd)
level including zero-point vibrational energy corrections.
mentioned. The same authors studied the pyrolysis of the
parent 1,2,4-trithiolane (3a) and reported only the appear-
ance of thioformaldehyde (12); thiosulfine 4a was not men-
tioned as a possible product of this reaction.
In our hands, careful analysis of the IR spectrum of the
pyrolysis products obtained from 8a provides clear evidence
for the presence of trace amounts of dithiirane (5a; a weak
IR band at 581.4 cm–1), formed side by side with isomeric
thiosulfine 4a. As already reported,[4] dithiirane 5a forms
Scheme 5.
The corresponding UV spectrum differed from that re-
from 4a via a 1,3-dipolar electrocyclization reaction. The corded for the pyrolysis products of 8a. The characteristic
ratio of 4a and 5a, formed in the gas phase, was shown to strong UV band of 4a was completely missing. Instead, the
depend on the temperature and the lower the temperature, bands located at λmax = 284 nm and 288 nm (partly resolved
the less of the cyclic product forms. In comparison with vibrational fine structure) as well as λmax = 242 nm proved
earlier reports[4,5,9] the pyrolysis temperature applied in the the formation of 13 and 10 (Figure 5).
Figure 4. The IR spectrum of matrix-isolated (argon, 10 K) high-vacuum flash pyrolysis products of 1,2,4-trithiolane 1-S-oxide (9a)
generated at 700 °C.
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G. Mloston, P. R. Schreiner et al.
FULL PAPER
Figure 5. The UV/Vis spectrum of matrix-isolated (argon, 10 K) high-vacuum flash pyrolysis products of 1,2,4-trithiolane 1-S-oxide (9a)
generated at 650 °C. * Traces of m-chlorobenzoic acid.
The formation of a mixture of 13c and 13t as the major
pyrolysis products of 9a suggests that the fragmentation of
the five-membered ring follows a completely different
mechanism in comparison with “symmetrical” 8a
(Scheme 6).
6-311+G(3df,3dp) level of theory (for details see Experi-
mental). The computed energy profile of the lowest energy
pathway is depicted in Figure 6. As the key intermediate we
postulate the sulfenic acid derivative 14, formed via 1,4-H
shift and simultaneous ring opening.
This process requires an activation energy of
32.2 kcalmol–1, which is in good agreement with the value
computed previously for the [2+3]-cycloreversion of 8a
(Figure 3). The second step, which requires a lower acti-
vation energy (19.0 kcalmol–1) results from the fragmenta-
tion of the intermediate 14 into the observed products 10
and 13. It is worth emphasizing that the proposed mecha-
nism is similar to that formulated in the reported transfor-
mation of disulfane S-oxide into a mixture of thioformal-
dehyde and a sulfenic acid derivative.[15]
Scheme 6.
In order to elucidate the most likely reaction mechanism,
we performed a computational study at the B3LYP/
Figure 6. Reaction profile (kcalmol–1) for the thermal decomposition of 1,2,4-trithiolane-1-S-oxide (9a) at the B3LYP/6-311+G(3df,3pd)
level of theory including zero-point vibrational energy corrections.
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Thermal Reactions of Regioisomeric 1,2,4-Trithiolane S-Oxides
Tjan, J. Agric. Food Chem. 1972, 20, 177–181; c) S. J. Wratten,
D. J. Faulkner, J. Org. Chem. 1976, 41, 2465–2467; d) Ch.-Ch.
Chen, Ch.-T. Ho, J. Agric. Food Chem. 1986, 34, 830–833; e)
M. Ritzau, M. Keller, P. Wessels, K. O. Stetter, A. Zeeck, Lie-
bigs Ann. Chem. 1993, 871–876; f) A. I. Rushdi, B. R. T. Si-
monei, Astrobiology 2005, 5, 749–769; g) F. Asinger, M. Thiel,
G. Liepfert, Justus Liebigs Ann. Chem. 1959, 627, 195–212; h)
H. Oshida, A. Ishi, J. Nakayama, J. Org. Chem. 2004, 69, 1695–
1703.
Conclusions
The present study shows that the pyrolysis of the re-
gioisomeric 1,2,4-trithiolane S-oxides 8a and 9a, irrespec-
tive of the structure of the isomer, results in the formation
of thioformaldehyde S-oxide (10) as one of two major prod-
ucts of the fragmentation process. In the case of “symmetri-
cal” S-oxide 8a, a [2+3]-cycloreversion leads to thioformal-
dehyde S-sulfide (5a) as the second major component of the
collected pyrolyzate.
On the other hand, the fragmentation of the “non-sym-
metrical” S-oxide 9a, does not involve a 1,3-dipolar inter-
mediate. Instead, a more complex fragmentation mecha-
nism, including migration of an H-atom, smoothly leads to
the formation of a s-cis and s-trans mixture of dithioformic
acid (13). Moreover, our studies show that vacuum pyroly-
sis of symmetrical 4-S-oxide derived from a 1,2,4-trithiol-
ane can be a useful method for the preparation of the corre-
sponding thiocarbonyl S-oxide (sulfine) that otherwise is
difficult to prepare or cannot be prepared by using known
procedures.[16] Sulfines are gaining growing importance in
modern organic synthesis.[16b]
[3] G. Mloston, H. Heimgartner, in: Targets in Heterocyclic Chem-
istry-Chemistry and Properties (Eds.: O. A. Attanasi, D. Spi-
nelli), Italian Society of Chemistry, Rome, 2006, vol. 10, p. 266–
300.
[4] G. Mloston, J. Romanski, H. P. Reisenauer, G. Maier, Angew.
Chem. Int. Ed. 2001, 40, 393–396.
[5] J. Romanski, H. P. Reisenauer, H. Petzold, W. Weigand, P. R.
Schreiner, G. Mloston, Eur. J. Org. Chem. 2008, 2998–3003.
[6] a) H. Petzold, S. Bräutigam, H. Görls, W. Weigand, U.
Uhlmann, R. Genner, W. Kiefer, J. Popp, A. Majchrzak, G.
Mloston, Inorg. Chim. Acta 2004, 357, 1897–1908; b) H. Pet-
zold, S. Bräutigam, H. Görls, W. Weigand, J. Romanski, G.
Mloston, Eur. J. Inorg. Chem. 2007, 5627–5632.
[7] E. Block, Angew. Chem. Int. Ed. Engl. 1992, 31, 1135–1178.
[8] H. Petzold, S. Bräutigam, H. Görls, G. Mloston, W. Weigand,
Eur. J. Inorg. Chem. submitted.
[9] P. R. Schreiner, H. P. Reisenauer, J. Romanski, G. Mloston, An-
gew. Chem. Int. Ed. 2009, 48, 8133–8136.
[10] a) D. E. Powers, C. A. Arrington, W. C. Harris, E. Block, V. F.
Kalasinsky, J. Phys. Chem. 1979, 83, 1890–1892; b) E. Suzuki,
R. Ishiguro, F. Watari, J. Mol. Struct. 1990, 238, 71–77; c) E.
Suzuki, F. Watari, Spectrochim. Acta, Sect. A 1995, 51, 779–
785.
Experimental Section
1,2,4-Trithiolane 4-oxide (8a) and 1,2,4-trithiolane 1-oxide (9a)
were prepared by oxidation of the parent 1,2,4-trithiolane (3a)[2a]
using known protocols.[6a]
[11] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr, T. Vreven,
K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tom-
asi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratch-
ian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Sal-
vador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D.
Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Ba-
boul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Lia-
shenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T.
Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, Gaussian 03, revision D.03,
Pittsburgh, 2003.
Matrix Isolation Experiments: Compounds 2a and 3a were sub-
jected to HVFP at 650 °C and 700 °C, respectively (empty quartz
tube, inner diameter: 8 mm, length of heating zone: 50 mm). The
products thus formed were trapped immediately thereafter on a
cold (10 K) CsI (or BaF2) window together with a large excess of
Ar or N2. These matrices were examined with FT-IR and UV/Vis
spectroscopy.
Computational Methods: All geometries were fully optimized and
characterized as minima or transition structures by means of ana-
lytical harmonic vibrational frequencies computations at the
B3LYP/6-311+G(3df,3pd) level of theory.[17] Unscaled zero-point
vibrational energy corrections were included in all relative energy
comparisons (kcalmol–1, relative to 9a). The Gaussian Program
Suite was used for all computations.[11]
[12] L. Breuer, G. D. Brabson, B. Meyer, J. Chem. Phys. 1965, 92,
1385–1389.
Acknowledgments
[13] H. Bock, B. Solouki, S. Mohmand, E. Block, L. K. Revelle, J.
Chem. Soc., Chem. Commun. 1977, 287–288.
This study was supported by the Deutscher Akademischer Aus-
tauschdienst (DAAD – Partnership University of Lodz and visiting
professor fellowship to M.L.M. and the Justus-Liebig University).
Authors G. M. and J. R. acknowledge financial support from the
Rector of the University of Lodz (Grant # 505/01).
[14] R. B. Bohn, G. D. Brabson, L. Andrews, J. Phys. Chem. 1992,
96, 1582–1589.
[15] E. Block, J. O’Connor, J. Am. Chem. Soc. 1974, 96, 3929–3944.
[16] a) B. Zwanenburg, T. J. G. Damen, H. J. F. Philipse, R. C.
De Laet, A. C. B. Lucassen, Phosphorus, Sulfur Silicon Relat.
Elem. 1999, 153–154, 119–136, and literature cited therein; b)
H. Ulrich, Cumulenes in Click Reactions, John Wiley & Sons,
New York, 2009, ch. 2.1.
[17] a) A. D. Becke, Phys. Rev. A 1988, 38, 3098–3100; b) C. Lee,
W. Yang, R. G. Parr, Phys. Rev. B 1993, 37, 785–789; c) B.
Miehlich, A. Savin, H. Stoll, H. Preuss, Chem. Phys. Lett. 1989,
157, 200–206.
[1] a) G. Mloston, H. Heimgartner, in: 1,3-Dipolar Cycloaddition
Chemistry toward Heterocycles and Natural Products (Eds.: A.
Padwa, W. H. Pearson), J. Wiley & Sons, New York, 2002, p.
315–360; b) G. Mloston, J. Romanski, C. Schmidt, H. P. Re-
isenauer, G. Maier, Chem. Ber. 1994, 127, 2527–2530.
[2] a) K. Morita, S. Kobayashi, Chem. Pharm. Bull. 1967, 15, 988–
993; b) A. W. Brinkmann, H. Copier, J. J. M. De Leuw, S. B.
Received: December 10, 2009
Published Online: February 22, 2010
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