1-Thiacyclooct-4-yne (=5,6-didehydro-3,4,7,8-tetrahydro-2H-thiocin), and its sulfoxide and its sulfone

Article abstract of DOI:10.1002/hlca.201200260

1-Thiacyclooct-4-yne (=5,6-didehydro-3,4,7,8-tetrahydro-2H-thiocin; 9) can be prepared from thiocan-5-one (6) in three steps by applying the so-called selenadiazole method. The heterocyclic alkyne can be oxidized to the corresponding sulfoxide 16 and sulf

Full text of DOI:10.1002/hlca.201200260

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1-Thiacyclooct-4-yne (¼ 5,6-Didehydro-3,4,7,8-tetrahydro-2H-thiocin), and
Its Sulfoxide and Its Sulfone
by Hans Schuhmacher, Bernhard Beile, and Herbert Meier*
Institute of Organic Chemistry, University of Mainz, Duesbergweg 10 – 14, D-55099 Mainz
(phone: þ 49-6131-3922605; fax: þ 49-6131-3925396; e-mail: hmeier@uni-mainz.de)
1-Thiacyclooct-4-yne (¼ 5,6-didehydro-3,4,7,8-tetrahydro-2H-thiocin; 9) can be prepared from
thiocan-5-one (6) in three steps by applying the so-called selenadiazole method. The heterocyclic
alkyne can be oxidized to the corresponding sulfoxide 16 and sulfone 17. Due to their geometrical strain,
all three cyclic alkynes show high reactivities in DielsꢀAlder and 1,3-dipolar cycloadditions. Moreover,
tetrathiafulvalenes can be prepared from 9 and 16 by the reaction with CS2.
Introduction. – Due to their high reactivity in addition and cycloaddition reactions,
strained cycloalkynes have a high actuality in click processes and bioorthogonal
reactions [1 – 14]. In the previous five years, many studies of azacyclooct-5-ynes (1)
appeared [8][11][15 – 42].
To the best of our knowledge, only one example exists for 1-oxacyclooct-4-ynes (2)
and one for 1-thiacyclooct-4-ynes 3, namely the tricyclic lactone 4 [42] and the bicyclic
sulfone 5 [43], respectively. This prompted us to report our results on the parent
compound 3.
Results and Discussion. – A convenient and high-yield preparation of strained
cyclic alkynes is based on the fragmentation of 1,2,3-selenadiazoles [44]. We used the
conversion of thiocanone 6 to the 1,2,3-selenadiazole 8 via the semicarbazone 7 [45].
Thermolysis of 8 on Cu powder gave the desired 1-thiacyclooct-4-yne (¼ 5,6-
didehydro-3,4,7,8-tetrahydro-2H-thiocin; 9) in almost quantitative yields (Scheme 1).
The 1,2,3-selenadiazole ring is sensitive towards oxidation. Therefore, we tried to
oxidize its precursor, the thiocanone 6 with NaIO4 to the sulfoxide 10 and with H2O2 to
the sulfone 11. The corresponding 1,2,3-selenadiazoles 14 and 15 were then obtained via
the semicarbazones 12 and 13, respectively. However, the thermal fragmentation of 14
and 15 failed. The volatility of the desired products is not high enough, so that
decompositions occurred in the hot zone.
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1. Preparation of 5-Thiacyclooctyne (9), and Its Sulfoxide (16) and Its Sulfone (17)
i) H2NNHCONH2, EtOH, AcONa. ii) SeO2, aqueous dioxane. iii) Cu, 165 – 1758, 100 Pa. iv) NaIO4, 08.
Therefore, we tried the alkaline fragmentation of the 1,2,3-selenadiazole 14 with
BuLi. The reaction led to a mixture of several Se-containing products. Selenio sulfoxide
18 was the major component, and the desired alkyne 16 was a minor product, in an
unsatisfying yield (Scheme 2).
Scheme 2
Finally, we realized that the stability of 1-thiacyclooct-4-yne (9) is sufficient for the
oxidation to its sulfoxide 16 and its sulfone 17. A fourfold excess of NaIO4 yielded 80%
of the oxidation-productmixture 16/17 in a 43 :37 ratio (Scheme 1). A higher excess of
NaIO4 increased the portion of the sulfone 17, but reduced the overall yield.
One- and two-dimensional NMR experiments were performed for the character-
1
ization of the new alkynes. A H,1H-shift-correlated NMR spectrum of rac-16 is
depicted in the Figure. The COSY 45 technique is suitable to distinguish between the
geminal and vicinal couplings [46]. A control for the assignment of geminal H-atoms
was achieved by a HSQC measurement.

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Figure. 1H,1H-COSY-45-NMR Spectrum of rac-16. The cross-peaks, which are characterized by a
positive slope, correspond to vicinal couplings, the cross-peaks marked with a negative slope correspond
to geminal couplings.
The 1H and 13C chemical shifts ofthe alkynes 9, 16, and 17 are compiled in the Table.
An easy anchor point for the interpretation of the NMR spectra is always CH2(3)
with two adjacent CH2 groups, CH2(2) and CH2(4). Due to the geometrical strain, the
sp-atoms C(5) and C(6) exhibit signals with relatively high d values. Their difference
Dd is small, which is in accordance with the small polarization of the CꢁC bonds and
the small regioselectivity of certain cycloadditions shown below.
The strain energies of the eight-membered rings of 9, 16, and 17 should be
comparable to that of cyclooctyne [44]. Hence, a high reactivity of 9, 16, and 17 in
cycloaddition reactions can be expected. We studied first the reactions with 2,3,4,5-
tetraphenylcyclopenta-2,4-dienone (19) at room temperature (Scheme 3). The Dielsꢀ

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Table. 1H- and 13C-NMR (CDCl3) Data of the Heterocyclic Alkynes 9, 16, and 17. d in ppm relative to
Me4Si as internal standard, J in Hz. The atom numbering corresponds to the 2H-thiocin nomenclature.
Compound
X
NMR CH2(2)
d(H) 2.76 – 2.72 2.19 – 2.12 2.24 – 2.19
d(C) 35.5 35.9 19.6
SO d(H)
CH2(3)
CH2(4)
C(5,6)
CH2(7)
2.35 – 2.29 2.97 – 2.93
94.1, 92.2 23.6 41.9
CH2(8)
9
S
rac-16
3.59 – 3.50 2.23 – 2.30 2.22 – 2.14
2.88 – 2.80 2.23 – 2.30 2.12 – 2.04
2.74 – 2.65 3.72 – 3.65
2.42 – 2.32 3.06 – 3.02
d(C) 62.0
SO2 d(H) 3.37 – 3.33 2.36 – 2.28 2.26 – 2.20
d(C) 61.9 25.3 18.7
25.8
18.5
92.1, 88.7 15.6
60.8
17
2.61 – 2.55 3.55 – 3.51
92.1, 88.9 16.0
59.9
Scheme 3
Alder reactions with subsequent aromatization according to the AlderꢀRickert rule
furnished the cycloadducts 20, 21, and 22, respectively, in reasonable-to-good yields.
From a synthetic point of view, the 1,3-dipolar cycloaddition, another [2p þ 4p]
cycloaddition, of 8, 16, and 17 with CH2N2 is more attractive. The tautomeric pyrazoles
23 – 28 were obtained (Scheme 4). The regioselectivities 23/24, 25/26, and 27/28 change
from 3 :2 for the reaction of 9 to 1:3 for the reaction of the sulfone 17. NOE
Experiments served for the distinction between the isomeric pyrazoles. Irradiation into
the signal of HꢀC(3) led to a positive NOE for CH2(4), which is a part of the ethylene
ꢂchainꢃ in 23, 25, and 27, whereas it is a part of the trimethylene ꢂchainꢃ in 24, 26, and 28.
Finally, we studied the behavior of the alkynes toward CS2 (Scheme 5). Alkyne 9
furnished, after 12 d in boiling CS2, tetrathiafulvalene 29 in low yield. This reaction type
is restricted to strained cycloalkynes and to electron-deficient linear alkynes [47][48].
A second reaction product of 9 (obtained in a yield of 16%) had the formula C23H30S7,
which corresponds to a 3 :2-adduct of 9 and CS2. Sulfoxide 16 gave 41% of the
tetrathiafulvalene 30. (Z/E)-Isomers have to be considered for 29 and 30. It is known
that the separation of (Z/E)-isomeric tetrathiafulvalenes is extremely difficult – even a
spectroscopic identification of these isomers is challenging [49]. We found a single set
of 13C-NMR signals among which the broad signal at d(C) 108.2 looked like two
superimposed signals for C(2) of 29. All other 13C-NMR signals of 29 did not show a

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Scheme 4
Scheme 5
splitting. Apart from the (Z/E)-isomerism, 30 exhibits a stereoisomerism owing to the
sulfoxide functionalities. Compounds syn-(E)-30 and anti-(Z)-30 are chiral, and anti-
(E)-30 and syn-(Z)-30 are meso-forms. Chiral tetrathiafulvalenes have recently gained
a high actuality [50][51]. Most of the 13C-NMR signals of 30 are split into pairs of equal
intensity. This corresponds to a syn-30/anti-30 ratio of 1:1. The resonance region at
d(C) 47.3 – 47.7 for one of the C-atoms neighboring to the SO group is even split into
four signals (syn-(Z), anti-(Z), syn-(E), and anti-(E); see Exper. Part). The other C-
atom neighboring to the SO group gives two signals of 52.6 ppm. Sulfone 17 did not
show an addition of CS2 with subsequent tetrathiafulvalene generation.
Conclusions. – In principle, three isomeric thiacyclooctynes (¼didehydrotetra-
hydro-2H-thiocins), and their sulfoxides and sulfones should exist. 1-Thiacyclooct-2-
yne and -3-yne were synthesized much earlier; here we report the preparation of 1-

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thiacyclooct-4-yne (9) by applying the selenadiazole method for the formation of the
CꢁC bond. Oxidation of 9 with NaIO4 generated the sulfoxide 16 and the sulfone 17.
Other sulfoxides or sulfones (n ¼ 0, 1) of thiacyclooctynes are not known. All three
heterocyclic alkynes, 9, 16, and 17, have high reactivities as 2p components toward 4p
components in DielsꢀAlder reactions and 1,3-dipolar cycloadditions. Moreover, the
tetrathiafulvalenes 29 and 30 could be obtained from 9 and 16 by the reaction with CS2.
The new cyclic alkynes 9, 16, and 17 are stimulating candidates for click reactions and
should be also interesting species for applications in bioorthogonal processes.
We are grateful to the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie for
financial support.
Experimental Part
General. 4,7,8,9-Tetrahydro-5H-thiocino[5,4-d][1,2,3]selenadiazole (8) was prepared as described in
[45] from 5-thiocanone (6) via semicarbazone 7. M.p.: Bꢀchi melting-point apparatus. IR: Beckman
1
Acculab 4; n¯ in cmꢀ1. H- and 13C-NMR spectra: AM-400 spectrometer from Bruker; CDCl3 as solvent
and Me4Si as internal standard; d in ppm and J in Hz. EI-MS: Finnigan-MAT-95 spectrometer, 70-eV
ionization energy; in m/z (rel. %).
Thermal Fragmentation of 1,2,3-Selenadiazole 8. To 2.0 g (31.5 mmol) of Cu powder, 467 mg
(2.0 mmol) of 8 dissolved in 2 ml of CH2Cl2 was added. The solvent was removed, and the residue was
heated under reduced pressure of 100 Pa to 170 ꢂ 58. 5-Thiacyclooctyne (5,6-didehydro-3,4,7,8-
tetrahydro-2H-thiocin; 9) distilled off as a colorless oil. Yield 235 mg (93%). IR (CDCl3): 2240
(CꢁC). NMR: see the Table. EI-MS: 126 (62, Mþ), 111 (51), 98 (52), 97 (100). According to the NMR
spectra, the product was pure, but, due to the volatility, a correct combustion analysis could not be
conducted.
Thiocan-5-one 1-Oxide (¼1-Oxo-1l4-thiocan-5-one) (10). The preparation was performed according
to a modified procedure described by Leonard and Johnson [54]. Thiocanone 8 (1.00 g, 6.93 mmol) was
dissolved in 10 ml of MeOH and added at 08 within 20 min to a soln. of 1.58 g (7.39 mmol) of NaIO4 in
10 ml of H2O. The product was isolated by extraction with CHCl3. The hygroscopic compound melted at
1058 (m.p. 91 – 928 [54]) and was analytically pure. Yield 1.05 g (95%). IR (CDCl3): 1030 (S¼O), 1695
1
2
3
3
(C¼O). H-NMR (CDCl3): 3.17 – 3.08 (ddd, J ¼ 14.4, J ¼ 8.8, J ¼ 2.6, 1 H each, CH2(2,8)); 2.73 – 2.57
(m, 1 H each, CH2(2,4,6,8)); 2.43 – 2.28 (m, 1 H each, CH2(3,4,6,7)); 2.15 – 2.04 (m, 1 H each, CH2(3,7)).
13C-NMR (CDCl3): 213.4 (C(5)); 51.1 (C(2,8)), 40.5 (C(4,6)); 18.1 (C(3,7)). EI-MS: 160 (7, Mþ), 118
(24), 90 (100). Anal. calc. for C7H12O2S (160.2): C 52.47, H 7.55; found: C 52.58, H 7.57.
Thiocan-5-one 1,1-Dioxide (¼1,1-Dioxo-1l6-thiocan-5-one) (11). The preparation was conducted
according to a modified procedure described by Leonard et al. [54][55]. Thiocanone 8 (1.00 g,
6.93 mmol) dissolved in 20 ml of acetone was treated with H2O2 (30%, 1.40 g, 73.6 mmol) at r.t. The
reaction was monitored by TLC (SiO2, CH2Cl2). At the end, the volatile parts were removed and the
residue was recrystallized from EtOH. Yield 904 mg (74%). M.p. 1068 ([55]: 124 – 1278). IR (KBr): 1690
(C¼O), 1325 (SO2), 1125 (SO2). 1H-NMR (CDCl3): 3.15 – 3.08 (m, 4 H, CH2(2,8)); 2.66 – 2.60 (m, 4 H,
CH2(4,6)); 2.33 – 2.24 (m, 4 H, CH2(3,7)). 13C-NMR (CDCl3): 212.8 (C(5)); 54.8 (C(2,8)); 39.8 (C(4,6));
19.9 (C(3,7)). EI-MS: 176 (8, Mþ), 70 (56), 55 42), 42 (100). The compound was identical with an
authentic sample [54][55].

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rac-2-(1-Oxidothiocan-5-ylidene)hydrazinecarboxamide (rac-12). Semicarbazide hydrochloride
(950 mg, 8.5 mmol) and AcONa (1.08 g, 13.2 mmol) were briefly refluxed in 20 ml of dry EtOH. The
hot filtrate was added to 10 (1.12 g, 7.0 mmol) dissolved in 5 ml of dry EtOH. After 2 h, the mixture was
cooled to 08. A crystalline precipitate was formed which was recrystallized from MeOH. Yield: 1.25 g
(82%). Colorless, fine crystals. M.p. 1388. IR (KBr): 1660 (C¼O), 1010 (S ¼ O). 1H-NMR ((D6)DMSO):
9.12 (s, NH); 6.26 (s, NH2); 3.10 – 3.01 (m, 1 H); 2.95 – 2.83 (m, 2 H); 2.63 – 2.52 (m, 2 H); 2.35 – 2.27 (m,
1 H); 2.27 – 2.08 (m, 3 H); 2.06 – 1.95 (m, 2 H); 1.92 – 1.81 (m, 1 H). 13C-NMR ((D6)DMSO): 157.1 (CO);
150.2 (C(5)); 51.3, 50.6 (C(2,8)); 35.6 (C(6)); 26.4 (C(4)); 18.9, 16.4 (C(3,7)). EI-MS: 217 (91, Mþ), 166
(56), 160 (100). Anal. calc. for C8H15N3O2S (217.3): S 44.22, H 6.69, N 19.34; found: C 44.16, H 6.98, N
19.29.
2-(1,1-Dioxidothiocan-5-ylidene)hydrazinecarboxamide (13). The preparation was performed as
described for 12. Ketone 11 (2.33 g, 13.2 mmol) yielded 2.46 g (80%) of 13. Colorless crystals. M.p. 1848
1
(MeOH). IR (KBr): 1680 (C¼O), 1110 (SO2). H-NMR ((D6)DMSO): 9.10 (s, NH); 6.30 (s, NH2);
3.22 – 3.14 (m, 2 H); 3.05 – 2.96 (m, 2 H); 2.54 – 2.45 (m, 2 H); 2.38 – 2.29 (m, 2 H); 2.08 – 1.95 (m, 4 H).
13C-NMR ((D6)DMSO): 157.2 (CO); 149.7 (C(5)); 53.6, 53.1 (C(2,8)); 35.5, 25.8 (C(4,6)); 20.8, 17.6
(C(3,7)). EI-MS: 233 (8, Mþ), 97 (24), 83 (37), 67 (30), 44 (43), 41 (100). Anal. calc. for C8H15N3O3S
(233.3): C 41.19, H 6.48, N 18.01; found: C 41.08, H 6.49, N 17.97.
rac-4,7,8,9-Tetrahydro-5H-thiocino[5,4-d][1,2,3]selenadiazole 6-Oxide (rac-14). To semicarbazone
12 (870 mg, 4.0 mmol) in 55 ml of dioxane, SeO2 (0.89 g, 8.0 mmol) and 0.25 ml of H2O were added. The
reaction in the dark was monitored by TLC (SiO2, toluene). After ca. 2 d, when the formation of gas
(CO2, NH3) was completed, the mixture was filtered and concentrated to ca. 3 ml. The remaining red oil
was purified by column chromatography CC (SiO2 (2 ꢃ 50 cm); toluene/AcOEt 10 :1). Yield: 510 mg
(51%). Beige crystals. M.p. 107 – 1088 (dec.). IR (KBr): 1300, 1275, 1025 (S ¼ O), 1000, 990, 780.
1H-NMR (CDCl3): 3.78 – 3.69 (m, 1 H of CH2(4)); 3.43 – 3.35 (m, 1 H, CH2(4)); 3.35 – 3.29 (m, 1 H,
CH2(9)); 3.29 – 3.25 (m, 1 H, CH2(9)); 3.25 – 3.20 (m, 1 H of CH2(5)); 3.09 – 3.03 (m, 1 H of CH2(7));
3.03 – 2.96 (m, 1 H, CH2(5)); 2.50 – 2.41 (m, 1 H, CH2(7)); 2.41 – 2.31 (m, 1 H, CH2(8)); 2.31 – 2.20 (m,
1 H, CH2(8)). 13C-NMR (CDCl3): 159.3 (C(9a)); 157.0 (C(3a)); 53.6, 48.1 (C(5,7)); 25.2, 23.6, 17.7
(C(4,8,9)). EI-MS: 205 (100, [M ꢀ C3H8]þ), 166 (38), 143 (11, [M ꢀ N2 ꢀ Se]þ), 124 (72), 91 (52). Anal.
calc. for C7H10N2OSSe (249.2): C 33.74, H 4.04, N 11.24; found: C 33.66, H 4.00, N 11.27.
4,7,8,9-Tetrahydro-5H-thiocino[5,4-d][1,2,3]selenadiazole 6,6-Dioxide (15). The preparation was
performed as described for 14. Semicarbazone 13 (0.93 g, 4.0 mmol) yielded 920 mg (87%) of 15. Yellow
crystals. M.p. 1638. IR (KBr): 1270 (SO2), 1165, 1110 (SO2), 795, 680. 1H-NMR (CDCl3): 3.60 – 3.54 (m,
CH2(4)); 3.47 – 3.42 (m, CH2(9)); 3.33 – 3.27 (m, CH2(5)); 2.89 – 2.83 (m, CH2(7)); 2.19 – 2.27 (m,
CH2(8)). 13C-NMR (CDCl3): 159.2, 156.1 (C(3a,9a)); 58.6, 53.3 (C(5,7)); 23.9, 22.9, 21.0 (C(4,8,9)). EI-
MS: 186 (1, [M ꢀ Se]þ), 119 (39), 92 (39), 91 (100). Anal. calc. for C7H10N2O2SSe: C 31.70, H 3.80, N
10.56; found: C 31.78, H 3.61, N 10.58.
Oxidation of 4,5-Didehydro-3,6,7,8-tetrahydro-2H-thiocine (9). Alkyne 9 (100 mg, 0.79 mmol) was
dissolved in 4 ml of MeOH and cooled to 08. NaIO4 (712 mg, 3.32 mmol) in 4 ml of H2O was added, and
the mixture was stirred overnight at 08. Further 6 ml of MeOH were added, and the mixture was cooled to
ꢀ 208. The inorg. salts precipitated and were filtered off. The soln. was dried (MgSO4), concentrated, and
subjected to CC (SiO2 (1 ꢃ 20 cm); AcOEt/EtOH 2 :1). The first fraction consisted of 46 mg (37%) of
4,5-didehydro-3,6,7,8-tetrahydro-2H-thiocine 1,1-dioxide (17). Colorless crystals. M.p. 1138. The second
fraction consisted of 48 mg (43%) of 4,5-didehydro-3,6,7,8-tetrahydro-2H-thiocine 1-oxide (rac-16).
Colorless crystals. M.p. 568.
Data of rac-16. IR (KBr): 1010 (S¼O), 2240 (CꢁC). 1H- and 13C-NMR: see the Table. EI-MS: 142
(54, Mþ), 91 (48), 79 (75), 77 (100). Anal. calc. for C17H10OS (142.2): C 59,12, H 7.09, S 22.54; found: C
59.23, H 7.11, S 22.50.
Data of 17. IR (KBr): 1110 (SO2), 1275, 1310 (SO2), 2260 (CꢁC). 1H- and 13C-NMR: see the Table.
EI-MS: 158 (100, Mþ), 117 (57), 83 (100). Anal. calc. for C7H10O2S (158.2): C 53.14, H 6.37; found: C
53.03, H 6.28.
Alkaline Fragmentation of rac-14). To rac-14 (250 mg, 1.0 mmol) in 10 ml of dry THF, 0.6 ml
(1.5 mmol) of a 15% soln. of BuLi in hexane was added at ꢀ 708. After 10 min, the reaction was
quenched by addition of 1.2 ml of MeOH and 1.2 ml of H2O. Extraction with CHCl3 at r.t. gave a yellow

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soln., which was dried (MgSO4), concentrated, and purified by CC (SiO2 (1 ꢃ 20 cm); AcOEt/EtOH
2 :1). The first fraction consisted of rac-18 (yield 60 mg (21%), yellow oil), and the second fraction of rac-
16 (yield 11.5 mg (8%)).
rac-(5E)-6-(Butylselanyl)-3,4,7,8-tetrahydro-2H-thiocine 1-Oxide (rac-18). IR (neat): 1025 (S¼O).
1H-NMR (CDCl3): 5.62 (t, 3J ¼ 9.0, HꢀC(5)); 3.34 – 3.25 (m, 1 H, CH2(8)); 3.25 – 3.15 (m, 1 H, CH2(2));
3.00 – 2.89 (m, 1 H each, CH2(7,8)); 2.80 – 2.73 (m, 1 H, CH2(2)); 2.67 (t, 3J ¼ 7.5, a-CH2); 2.60 – 2.52 (m,
1 H, CH2(7)); 2.44 – 2.33 (m, 1 H of CH2(4)); 2.20 – 2.08 (m, 1 H, CH2(4)); 2.02 – 1.91 (m, 1 H, CH2(3));
1.62 (quint., 3J ¼ 7.5, b-CH2); 1.38 (sext., 3J ¼ 7.8, g-CH2); 0.90 (t, 3J ¼ 7.8, Me). 13C-NMR (CDCl3): 130.9
(C(6)); 128.8 (C(5)); 52.9, 51.4 (C(2,8)); 31.9, 27.2, 25.3, 25.1, 23.0, 23.0 (other CH2); 13.5 (Me). EI-MS:
280 (3, Mþ, Se pattern), 143 (100, [M ꢀ C4H9]þ). Anal. calc. for C11H20OSSe (279.3): C 47.30, H 7.22;
found: C 47.43, H 7.12.
Reaction of 9, rac-16, and 17 with 2,3,4,5-Tetraphenylcyclopenta-2,4-dien-1-one (19). Alkyne 9, rac-
16 or 17 (0.20 mmol), and 19 (154 mg, 0.40 mmol) were stirred overnight at r.t. in 4 ml of toluene. The
violet soln. was concentrated and purified by CC (SiO2 (1 ꢃ 60 cm); toluene for 20, AcOEt/EtOH 1:1 for
21, and CHCl3 for 22).
1,4,5,6-Tetrahydro-7,8,9,10-tetraphenyl-2H-3-benzothiocine (20). Yield: 45 mg (46%). Colorless
1
crystals. M.p. 2248. IR (KBr): 700, 740. H-NMR (CDCl3): 7.19 – 7.00 (m, 10 arom. H); 6.80 – 6.66 (m,
10 arom. H); 3.10 – 2.98 (m, CH2(1,6)); 2.68 – 2.61, 2.60 – 2.50 (2m, CH2(2,4)); 1.65 – 1.56 (m, CH2(5)).
13C-NMR (CDCl3): 141.2, 141.2, 141.1, 141.0, 140.7, 140.6, 139.9, 139.6, 137.7, 137.2 (arom. Cq); 131.1, 130.7,
130.4, 127.4, 127.2, 126.3, 126.1, 126.0, 125.0 (arom. CH, partly superimposed); 35.1, 33.9, 32.5, 31.0, 27.5
(aliph. CH2). EI-MS: 482 (89, Mþ), 440 (100). Anal. calc. for C35H30S: C 87.09, H 6.26; found: C 87.21, H
6.52.
1,4,5,6-Tetrahydro-7,8,9,10-tetraphenyl-2H-3-benzothiocine 3-Oxide (21). Yield 59 mg (59%). Color-
less crystals. M.p. 2278. IR (KBr): 700, 740, 1025 (S¼O). 1H-NMR (CDCl3): 7.34 – 6.97 (m, 10 arom. H);
6.82 – 6.66 (m, 10 arom. H); 3.31 – 3.15, 3.08 – 2.85, 2.81 – 2.63 (3m, CH2(1,2,4,6)); 1.97 – 1.79 (m, CH2(5)).
13C-NMR (CDCl3): 141.5, 141.4, 140.8, 140.4, 140.3, 140.2, 140.1, 140.1, 135.7, 135.4 (arom. Cq); 130.9,
130.3, 130.2, 130.1, 127.7, 127.5, 127.3, 126.5, 126.4, 126.3, 125.2 (arom. CH, partly superimposed); 58.3,
55.3 (C(2,4)); 28.5, 23.5, 22.8 (C(1,5,6)). EI-MS: 498 (97, Mþ), 407 (100). Anal. calc. for C35H30OS
(498.7): C 84.30, H 6.06; found: C 84.05, H 6.05.
1,4,5,6-Tetrahydro-7,8,9,10-tetraphenyl-2H-3-benzothiocine 3,3-Dioxide (22). Yield: 87 mg (84%).
Colorless crystals. M.p. 2558. IR (KBr): 700, 740, 1120 (SO2), 1280 (SO2). 1H-NMR (CDCl3): 7.21 – 7.00
(m, 10 arom. H); 6.83 – 6.68 (m, 10 arom. H); 3.15 – 2.97 (m, CH2(1,2,4,6)); 1.71 – 1.67 (m, CH2(5)).
13C-NMR (CDCl3): 141.6, 141.5, 141.0, 140.4, 140.2, 140.1, 140.0, 139.9, 135.5, 135.2 (arom. Cq); 130.8,
130.2, 129.9, 127.8, 127.5, 126.7, 126.5, 125.3 (arom. CH, partly superimposed); 58.7, 52.5 (C(2,4)); 27.1,
24.6, 22.6 (C(1,5,6)). EI-MS: 514 (43, Mþ), 349 (56), 348 (50), 347 (100). Anal. calc. for C35H30O2S
(514.7): C 81.68, H 5.87; found: C 81.51, H 5.68.
Reaction of 9, rac-16, and 17 with CH2N2. To 0.50 mmol of the 9, rac-16, or 17, dissolved in 10 ml of
dry Et2O, a 0.1m soln. of CH2N2 in Et2O (ca. 10 ml, ca. 1.0 mmol) was added. The yellow soln. was stirred
for 24 h, and then the excess CH2N2 was removed by passing compressed air through the flask (the air is
then introduced to a trap with aq. HCl). The remaining soln. was concentrated, and the product was
purified by CC (SiO2 (2 ꢃ 38 cm); Et2O/petroleum ether (b.p. 40 – 708) 3 :1). The separation of the
regioisomeric cycloadducts 23/24, rac-25/rac-26, and 27/28 by CC was not successful. The correlation of
the NMR signals was based on NOE experiments and 1H,1H-COSY 45 spectra.
1,4,5,7,8,9-Hexahydrothiocino[5,4-c]pyrazole (23)/1,4,5,6,8,9-Hexahydrothiocino[4,5-c]pyrazole
1
(24). Yield: 49 mg (58%). Colorless crystals. M.p. 968. Ratio 23/24 according to the H-NMR signals
60 :40. 1H-NMR (CDCl3) of 23: 7.25 (s, HꢀC(3)); 3.04 – 2.99 (m, CH2(9)); 2.88 – 2.85 (m, CH2(4)); 2.67 –
2.63 (m, CH2(5)); 2.47 – 2.43 (m, CH2(7)); 1.89 – 1.81 (m, CH2(8)). 1H-NMR (CDCl3) of 24: 7.28 (s,
HꢀC(3)); 3.07 – 3.03 (m, CH2(9)); 2.76 – 2.81 (m, CH2(4)); 2.71 – 2.67 (m, CH2(8)); 2.43 – 2.39 (m,
CH2(6)); 1.78 – 1.70 (m, CH2(5)). 13C-NMR (CDCl3) of 23: 144.8 (C(9a)); 133.4 (C(3a)); 118.1 (C(3));
37.3, 31.4, 31.2, 28.0, 21.3 (C(4,5,7,8,9)). 13C-NMR (CDCl3) of 24: 146.4 (C(9a)); 132.4 (C(3a)); 116.9
(C(3)); 35.4, 32.4, 31.5, 30.1, 19.2 (C(4,5,6,8,9)). EI-MS: 168 (100, Mþ), 121 (39), 107 (50), 94 (84). Anal.
calc. for C8H12N2S (168.3): C 57.11, H 7.19, N 16.65; found: C 57.00, H 7.18, N 16.68.

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Helvetica Chimica Acta – Vol. 96 (2013)
rac-1,4,5,7,8,9-Hexahydrothiocino[5,4-c]pyrazole 6-Oxide (25)/rac-1,4,5,6,8,9-Hexahydrothioci-
no[4,5-c]pyrazole 7-Oxide (26). Yield: 45 mg (49%). Viscous oil. Ratio 25/26 according to the
1H-NMR signals 50 :50. IR (neat): 1010 (S¼O). 1H-NMR (CDCl3): 7.35 (s, HꢀC(3)) and 7.25 (s,
HꢀC(3)); 3.32 – 2.95 (m, 9 H), 2.92 – 2.78 (m, 2 H), 2.73 – 2.62 (m, 4 H), 2.52 – 2.42 (m, 1 H), 2.21 – 2.05
(m, 3 H), 2.04 – 1.93 (m, 1 H). 13C-NMR (CDCl3): 145.3, 144.6 (C(9a)); 132.5, 130.9 (C(3a)); 115.6, 115.5
(C(3)); 55.8, 54.0, 51.5, 51.2 (C(5,7) of 25 and C(6,8) of 26); 25.0, 23.6, 23.2, 21.1, 18.2, 16.0 (C(4,8,9) of
25 and C(4,5,9) of 26). EI-MS: 184 (22, Mþ), 108 (12), 85 (66), 84 (21), 83 (100). Anal. calc. for
C8H12N2OS (184.3): C 52.15, H 6.56, N 15.20; found: C 52.40, H 6.85, N 15.17.
1,4,5,7,8,9-Hexahydrothiocino[5,4-c]pyrazole 6,6-Dioxide (27)/1,4,5,6,8,9-hexahydrothiocino[4,5-
c]pyrazole 7,7-Dioxide (28). Yield 38 mg (38%). Viscous oil. Ratio 27/28 according to the 1H-NMR
signals 25 :75. IR (CHCl3): 1105 (SO2), 1270 (SO2). 1H-NMR (CDCl3, 27): 7.40 (s, HꢀC(3)); 3.21 – 3.14,
1
3.02 – 2.90, 2.03 – 2.01 (3m, CH2(4,5,7,8,9)). H-NMR (CDCl3, 28): 7.32 (s, HꢀC(3)), 3.28 – 3.23, 3.21 –
3.14, 2.96 – 2.88, 2.83 – 2.77, 2.01 – 1.93 (5m, CH2(4,5,6,8,9)). 13C-NMR (CDCl3, 27): 145.2 (C(9a));
130.2 (C(3a)); 116.1 (C(3)); 59.7, 52.9 (C(5,7)); 23.1, 21.4, 18.2 (C(4,8,9)). 13C-NMR (CDCl3, 28): 147.0
(C(9a)); 129.8 (C(3a)); 115.9 (C(3)); 58.2, 52.5 (C(6,8)); 24.5, 20.8, 19.1 (C(4,5,9)). EI-MS: 200 (1, Mþ),
84 (93), 66 (100). Anal. calc. for C8H12N2O2S (200.3): C 47.98, H 6.04, N 13.99; found: C 47.88, H 6.30, N
14.02.
Reaction of the 9 or rac-16 with CS2. Alkyne (1.0 mmol) and CS2 (4 ml, 5.08 g, 66.7 mmol) were
refluxed under N2 for 12 – 15 d. The colorless soln. turned orange and then redbrown. The soln. was
concentrated, and the products were purified by CC (SiO2 (3 ꢃ 40 cm); toluene/petroleum ether
(b.p. 40 – 708) 2 :1 for 29 and AcOEt/EtOH 1:1 for product 30).
(2Z/E)-4,7,8,9-Tetrahydro-2-(4,7,8,9-tetrahydro-5H-1,3-dithiolo[4,5-d]thiocin-2-ylidene)-5H-1,3-di-
thiolo[4,5-d]thiocine; 29). Yield: 53 mg (13%). Red-orange crystals. M.p. 1958. IR (CDCl3): 1270, 1445.
1H-NMR (CDCl3): 2.75 – 2.63 (m, CH2(4,5,7,9,4’,5’,7’,9’)); 1.91 – 1.81 (m, CH2(8,8’)). 13C-NMR (CDCl3):
128.8, 128.7 (C(3a,9a,3aꢃ,9aꢃ)); 108.2 (C(2,2’)); 34.7, 32.0, 31.4, 31.1, 25.1 (C(4,5,7,8,9,4’,5’,7’,8’,9’)). EI-MS:
404 (100, Mþ), 202 (4, M2þ). Anal. calc. for C16H20S6 (404.7): C 47.49, H 4.98; found: C 47.39, H 4.89. As
second fraction, a dark-red solid C23H30S7 (85 mg, 16%) was obtained. The structure was not determined.
syn-(2Z/E)- and anti-(2Z/E)-4,7,8,9-Tetrahydro-2-(4,7,8,9-tetrahydro-6-oxido-5H-1,3-dithiolo[4,5-
d]thiocin-2-ylidene)-5H-1,3-dithiolo[4,5-d]thiocine 6-Oxide; 30). Yield: 179 mg (41%). Red-orange
solid. M.p. 2048. IR (KBr): 1010, 1445, 1625. 1H-NMR (CDCl3): 3.30 – 3.19 (m, 2 H); 3.19 – 3.07 (m, 4 H);
3.00 – 2.89 (m, 2 H); 2.88 – 2.73 (m, 4 H); 2.55 – 2.45 (m, 2 H); 2.42 – 2.30 (m, 2 H); 2.26 – 2.20 (m, 2 H);
2.20 – 2.13 (m, 2 H) (CH2 groups). 13C-NMR (CDCl3): 129.0, 129.0, 127.3, 127.2 (C(3a,9a,3aꢃ,9aꢃ)); 108.3,
108.2 (C(2,2’)); 52.6, 52.6, 47.7, 47.6, 47.4, 47.3 (C(5,7,5’,7’)); 26.5, 26.4, 23.0, 22.8, 18.9, 18.8
(C(4,8,9,4’,8’,9’)). EI-MS: 436 (30, Mþ), 142 (100), 97 (56), 85 (49), 72 (58), 71 (84). Anal. calc. for
C16H20O2S6 (436.7): C 44.01, H 4.62, S 44.05; found: C 43.89, H 4.61, S 43.87.
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Received May 16, 2012