Reactions of stable α-chlorosulfanyl chlorides with C = S-functionalized compounds

Article abstract of DOI:10.1002/hlca.200390183

The smooth reaction of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (3) with 3,4,5-trisubstituted 2,3-dihydro-1H-imidazole-2-thiones 8 and 2-thiouracil (10) in CH₂Cl₂/Et₃N at room temperature yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of Cl^- of the sulfanyl chloride by the S-atom of the heterocyclic thione. The analogous reaction of 3-cyclohexyl-2,3-dihydro-4,5-diphenyl-1H-imidazole-2-thione (8b) and 10 with the chlorodisulfanyl derivative 16 led to the corresponding trisulfanes 17 and 18 (Scheme 4), respectively. On the other hand, the reaction of 3 and 4,4-dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione (12) in CH₂Cl₂ gave only 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-one (13) and the trithioorthoester derivative 14, a bis-disulfane, in low yield (Scheme 3). At - 78°, only bis(1-chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)polysulfanes 15 were formed. Even at -78°, a 1:2 mixture of 12 and 16 in CH₂Cl₂ reacted to give 13 and the symmetrical pentasulfane 19 in good yield (Scheme 5). The structures of 11, 14, 17, and 18 have been established by X-ray crystallography.

Full text of DOI:10.1002/hlca.200390183

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Reactions of Stable a-Chlorosulfanyl Chlorides with CˆS-Functionalized
Compounds
by Agnieszka Majchrzaka)1), Aleksandra Janczakb)2), Grzegorz Mloston¬*b), Anthony Lindena),
and Heinz Heimgartner*a)
a) Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
b
¬
¬
¬
¬
) Section of Heteroorganic Compounds, University of Ëodz, Narutowicza 68, PL-90-136 Ëodz
The smooth reaction of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (3) with 3,4,5-
trisubstituted 2,3-dihydro-1H-imidazole-2-thiones 8 and 2-thiouracil (10) in C HCl2/Et3N at room temperature
2
yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of ClÀ of
the sulfanyl chloride by the S-atom of the heterocyclic thione. The analogous reaction of 3-cyclohexyl-2,3-
dihydro-4,5-diphenyl-1H-imidazole-2-thione (8b) and 10 with the chlorodisulfanyl derivative 16 led to the
corresponding trisulfanes 17 and 18 (Scheme 4), respectively. On the other hand, the reaction of 3 and 4,4-
dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione (12) in
C HCl2 gave only 4,4-dimethyl-2-phenyl-1,3-thiazol-
2
5(4H)-one (13) and the trithioorthoester derivative 14, a bis-disulfane, in low yield (Scheme 3). At À 788,
only bis(1-chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)polysulfanes 15 were formed. Even at À 788, a 1:2
mixture of 12 and 16 in CH2Cl2 reacted to give 13 and the symmetrical pentasulfane 19 in good yield (Scheme 5).
The structures of 11, 14, 17, and 18 have been established by X-ray crystallography.
Introduction. Recently, it has been shown that the reaction of 2,2,4,4-tetramethyl-
3-thioxocyclobutanone (1) and the corresponding dithione 2 with Cl2 at room
temperature leads smoothly to stable a-chlorosulfanyl chlorides 3 and 4, respectively
[1] (Scheme 1). Replacement of gaseous Cl2 by PCl5 afforded the same products, which,
surprisingly, were stable during aqueous workup [2]. Compounds 3 and 4 react easily
with thioacetic acid to give acetylated disulfanes [1]. Furthermore, they add to 1 and
adamantanethione yielding the corresponding a,a'-dichloro-disulfanes [2][3].
In contrast to the unexpected formation of a-chlorosulfanyl chlorides from 1 and 2,
and PCl5, the analogous reaction with 2,2,4,4-tetramethylcyclobutane-1,3-dione (5) was
reported as a convenient synthesis of 1,1,3,3-tetrachloro-2,2,4,4-tetramethylcyclobu-
tane (6) [4]. Surprisingly, the expected formation of dichloro ketone 7 has not been
mentioned. On the other hand, 7 was used in a photochemical study, but neither details
of its preparation nor physico-chemical properties were mentioned [5].
In the present paper, we describe the results of the reactions of 3 and the
corresponding disulfanyl chloride 16 with some compounds containing CˆS groups.
Results. The starting material 3 was prepared by the known method with PCl5 [2].
In analogy to the reported smooth reaction 5 ! 6, we treated 3 with excess PCl5 in
1
)
)
Part of the planned Ph.D. thesis of A. M., Universit‰t Z¸rich.
2
¬
¬
In part from the Diploma thesis of A. J., University of Ëodz, 2002.

Helvetica Chimica Acta Vol. 86 (2003)
2273
Scheme 1
refluxing CCl4. After 18 h and aqueous workup, 3 was the only compound obtained.
Based on this result, we repeated the reaction of 5 with a threefold excess of PCl5 in
boiling CCl4, and the progress of the reaction was monitored by 1H-NMR spectroscopy.
After 1 h, the dichloro derivative 7 was the main product, accompanied by 5 and 6
(ratio 7:1:2). Prolonged heating (3 h) led to a 3 :1 mixture of 7 and 6, and, only after
18 h, 6 was the main product. The analogous reaction of 5 with 1.1 equiv. of PCl5
afforded after 6 h a ca. 9 :1 mixture of 7 and 6. Their separation by fractional
crystallization was unsuccessful, and chromatography on SiO2 led to almost complete
hydrolysis of 7. Nevertheless, small amounts of pure 7 were obtained and fully
characterized.
Reactions with a-Chlorosulfanyl Chloride 3. The easily available 2,3-dihydro-1H-
imidazole-2-thiones 8 [6] reacted smoothly with 3 in the presence of Et3N at room
temperature. After a few min, 8 was completely consumed (TLC), and, after aqueous
workup, the crude mixture was analyzed by 1H-NMR spectroscopy. In each case, only
one product was formed, which was identified as a disulfane of type 9 (Scheme 2).
Purification by crystallization gave yellowish solids in good yields. The characteristic
1
data of 9a are a strong IR absorption at 1791 cmÀ1 (CˆO) and, in the H-NMR
spectrum, two signals for two Me groups at 1.61 and 1.55 ppm, attributed to the
tetramethylcyclobutane moiety, and three Me signals at 2.36, 2.37, and 3.86 ppm for the
trimethylimidazole. In the 13C-NMR spectrum, the signals of CˆO, and C(2) and C(4)
of the tetramethylcyclobutanone appear at 216.2 and 69.2 ppm, respectively, and C(3)
.
‡
absorbs at 86.5 ppm. The EI-MS shows the molecular ion (M ) at m/z 332.

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Scheme 2
The analogous reaction of 3 with thiouracil (10) gave again only one product,
isolated in 78% yield as colorless crystals. The structure of 11 (Scheme 2) was
elucidated on the basis of its spectroscopic data and elemental analysis, and confirmed
by an X-ray crystal-structure determination (Fig. 1).
Disulfanes with heterocyclic residues, in particular those with imidazoles, are well
known as biologically active compounds (cf. [8][9] and refs. cit. therein). The method
used for the synthesis of symmetrical disulfanes is the oxidation of the corresponding
imidazole-thiones. Reactions with sulfanyl chlorides leading to unsymmetrical disul-
Fig. 1. ORTEP Plot [7] of the molecular structure of 11 (50% probability ellipsoids, arbitrary numbering of
atoms)

Helvetica Chimica Acta Vol. 86 (2003)
2275
fanes have also been reported [9 11], but, to the best of our knowledge, no reaction
with an a-chlorosulfanyl chloride has been described.
In the last few years, 1,3-thiazole-5(4H)-thiones of type 12 have frequently been
used as model compounds for reactions with CˆS groups [12][13]. Unlike imidazole-
thiones 8 and thiouracil (10), no tautomerism to −thiol× derivatives is possible in the case
of 12; its structure corresponds rather to that of a dithiolactone (cyclic dithioester). As
reactions of dithioesters with a-chlorosulfanyl chlorides are almost unknown, we
decided to include 12 in the present study.
The reaction of equimolar amounts of 3 and 4,4-dimethyl-2-phenyl-1,3-thiazole-
5(4H)-thione (12) in C HCl2 at room temperature for 24 h afforded a mixture of 12, the
2
corresponding oxo compound 13, and a product 14, containing both starting materials
(Scheme 3)3). After chromatographic separation and crystallization from hexane, 14
was obtained as colorless crystals. In the IR spectrum, a very strong band at 1785 cmÀ1
confirmed the presence of the cyclobutanone unit. The NMR spectra revealed typical
signals for the 2,5-dihydro-1,3-thiazole ring (Ph substituent, CˆN absorption at
160.0 ppm). Both the 1H- and 13C-NMR spectra showed five singlets for two Me groups
each. These data indicated that structure 14 contains two cyclobutanone units and one
1,3-thiazole ring. The elemental analysis suggested that 14 also contains five S-atoms.
Finally, an X-ray crystal-structure determination established the structure of 14
(Fig. 2), which is a trithioorthoester derivative of 1,3-thiazole-5(4H)-thione 12.
Scheme 3
Reactions with a-Chlorodisulfanyl Chloride 16. As already reported, the reaction of
1 with SCl2 is the method of choice for preparing the stable a-chlorodisulfanyl chloride
16 [2]. As an extension of the experiments described above, reactions of 16 with 8b and
10, as well as with 12, were carried out. In the cases of 8b and 10, under typical
conditions (CH2Cl2, Et3N, r.t.) only one product, 17 and 18, respectively, was formed.
3
)
The reaction of 3 and 12 in a ratio of 2:1 at À 788 led to the disappearance of 12 after 4 h. Workup after
stirring for 24 h at room temperature gave 13, and a mixture of di-, tri-, and tetrasulfanes of type 15 (cf.
[2][3]).

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Helvetica Chimica Acta Vol. 86 (2003)
Fig. 2. ORTEP Plot [7] of the molecular structure of one of the two symmetry-independent molecules of 14 (50%
probability ellipsoids, arbitrary numbering of atoms)
Whereas 17 was isolated as yellow crystals, the crystals of 18 were colorless (Scheme 4).
The structures of the two products were established on the basis of their spectroscopic
data, elemental analyses, and by X-ray crystallography (Fig. 3). These compounds are
the first examples of imidazole and uracil derivatives with a trisulfanyl side chain.
Disulfanyl chloride 16 reacted with 12 in CH2Cl2 even at À788. After stirring a 1:2
mixture for 6 h at this temperature and 24 h at room temperature, chromatographic
separation gave 13 and pentasulfane 19 (Scheme 5) in comparable yields (ca. 76%).
The structure of 19 was unambigously determined by X-ray crystallography4). An
analogous experiment carried out at room temperature led to similar results. In both
cases, no product containing fragments of both starting materials could be detected.
Discussion. Sulfanyl chlorides are well-known as electrophilic reaction partners
[14]. The presented results show that a-chlorosulfanyl chloride 3 reacts with imidazole-
2-thiones analogously to typical sulfanyl chlorides, e.g., (tert-butyl)- or (2-nitro-
phenyl)sulfanyl chlorides (cf. [9 11]), to yield unsymmetrical disulfanes 9. The
mechanism of the formation of 9 corresponds to known reactions of imidazole-2-
thiones (cf. [15]), i.e., the nucleophilic attack occurs via the S-atom. The reactions of
imidazole-2-thione 8b and thiouracil (10) with disulfanyl chlorides, which have not
been reported to date, follow the same reaction pathway, leading to trisulfanes. It is
worth mentioning that products 9, 11, 17, and 18 are stable compounds, although they
contain an sp3-C-atom bearing an S- and a Cl-atom. This stability like that of 3 [1]
can be rationalized by the unfavorable formation of an sp2-C-atom in a small ring [16].
4
)
The structure determination will be published elsewhere.

Helvetica Chimica Acta Vol. 86 (2003)
2277
Fig. 3. ORTEP Plots [7] of the molecular structures of a) 17 and b) 18 (50% probability ellipsoids, arbitrary
numbering of atoms)
The driving force for the formation of 9 and 11 is the elimination of HCl from the
intermediate thiocarbonylium chlorides of type 20.
In the case of the reactions with 12, the initial formation of similar thiocarbonylium
salts of type 21 is likely. However, in these cases, no stabilization via deprotonation is
possible. Therefore, the reactive salts 21 react with traces of H2O and decompose into
13 and polysulfanes 22. According to this interpretation, 1,3-thiazole-5(4H)-thiones can
be used as efficient S-transfer reagents. This procedure can be regarded as an extension
of Senning×s method, where the elongation of a sulfane chain is achieved by the reaction
of a sulfanyl chloride with thioacetic acid and subsequent deacylation using morpholine
[17]. The in situ formed sulfanes 22 can easily react with sulfanyl chlorides 3 and 16
leading to symmetrical sulfanes 15 and 19, respectively. In the case of the reaction of 3
with 12, 22 (n ˆ 1) apparently reacts faster with the thiocarbonylium salt 21 (n ˆ 1) to
give 14.

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Scheme 4
Scheme 5
With the aim of obtaining further support for the above interpretation, 3 was also
reacted with thiobenzophenone in CH2Cl2 at room temperature. After a few min, the
blue color of the mixture disappeared, and, after typical workup, benzophenone was
isolated chromatographically as the sole product [18]. In line with our proposals, the
initially formed 23, which cannot be stabilized by deprotonation, is easily hydrolyzed by
traces of H2O.

Helvetica Chimica Acta Vol. 86 (2003)
2279
In conclusion, a-chlorosulfanyl chlorides 3 and 16 smoothly form new S,S bonds
with CˆS groups to give reactive thiocarbonylium salts. Further conversion depends on
the structure of the thiocarbonyl substrate.
We thank the analytical sections of our institutes for spectra and elemental analyses, and Mrs. M. Celeda,
¬
¬
¬
¬
Ëodz, for excellent technical assistance. Financial support of the Rector of the University of Ëodz (Research
Grant No. 505/465), the Swiss National Science Foundation, and F. Hoffmann-La Roche AG, Basel, is gratefully
acknowledged.
Experimental Part
1. General. See [19]. M.p.: in capillary; Melt-Temp II apparatus (Aldrich); uncorrected. IR (KBr): NEXUS
1
FT-IR spectrophotometer. H- and 13C-NMR (CDCl3): Bruker-AC-300 (300 and 75.5 MHz, resp.) or Tesla BS
687 (80 and 20 MHz, resp.). MS: Finnigan-MAT-90 (EI, 70 eV, or CI (NH3)). Elemental analyses were
performed by the Mikroanalytisches Laboratorium des Organisch-chemischen Instituts der Universit‰t Z¸rich.
2. Starting Materials. 2,2,4,4-Tetramethylcyclobutane-1,3-dione (5) (dimethylketene dimer) was prepared by
treatment of isobutyryl chloride with Et3N by using CH2Cl2 as solvent [20]. Thioketones 1 and 2 were obtained
from 5 by treatment with P4S10 in pyridine according to a known protocol [21]. 2,3-Dihydro-1H-imidazole-2-
thiones 8 were obtained from the corresponding imidazole N-oxides by treatment with dithione 2 as described in
[22]. 3-Chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (3) and 3-chloro-3-(chlorodisulfanyl)-
2,2,4,4-tetramethylcyclobutanone (16) were synthesized from 1 and PCl5 and SCl2, respectively; the crude
products were purified by distillation in vacuo as described in [2]. The synthesis of 4,4-dimethyl-2-phenyl-1,3-
thiazole-5(4H)-thione (12) was performed according to [23].
3. Reaction of 5 with PCl5. A soln. of 5 (2.0 g, 14 mmol) and PCl5 (5.9 g, 28 mmol) in CCl4 (10 ml) was
1
heated under reflux, and the progress of the reaction was monitored by H-NMR. After 3 h, 5 was completely
converted into a mixture 7/6 (ca. 3 :1). The soln. was cooled to r.t. and poured on ice/H2O. The org. phase was
washed three times with an aq. soln. of NaHCO3 (5%) and subsequently dried (MgSO4). The product mixture
was separated chromatographically (CC; SiO2, petroleum ether with increasing amounts of CH2Cl2).
Tetrachlorocyclobutane 6 was isolated as the less polar fraction, followed by 7, which partially hydrolyzed
during chromatography to give 5.
1,1,3,3-Tetrachloro-2,2,4,4-tetramethylcyclobutane (6). Yield: 290 mg (8%). Colorless crystals. M.p. 232
2348 (MeOH) ([4]: 234 2368, MeOH). IR: 3011s, 2984s, 2943s, 1470vs, 1455s, 1443s, 1387m, 1371m, 1205m,
952m, 881vs, 839vs, 517s, 431s. 1H-NMR: 1.54 (s, 4 Me). 13C-NMR: 26.2 (q, 4 Me); 61.6 (s, C(2), C(4)); 96.9
(s, C(1), C(3)).
3,3-Dichloro-2,2,4,4-tetramethylcyclobutan-1-one (7). Yield: 680 mg (25%). Colorless plates. M.p. 72 738
(MeOH, dry ice). IR: 2983s, 2939m, 2872w, 1794vs and 1769s (CˆO), 1462s, 1451s, 1383m, 1369m, 1249m,
1030s, 935vs, 837s. 1H-NMR: 1.43 (s, 4 Me). 13C-NMR: 22.8 (q, 4 Me); 70.1 (s, C(2), C(4)); 94.1 (s, C(3)); 215.3
(s, CˆO). Anal. calc. for C8H12Cl2O (195.09): C49.25, H 6.20; found: C49.50, H 6.38.
4. Reactions of 8a 8c with 3. A soln. of 3 (272 mg, 1.2 mmol) in CH2Cl2 (2 ml) was added in portions at r.t.
to a stirred soln. of 8 (1 mmol) and Et3N (2 ml, 1.45 g, 14.3 mmol) in CH2Cl2 (2 ml). When the addition was
complete, stirring was continued for 15 min, and subsequently CH2Cl2 (20 ml) was added. The mixture was
washed with H2O (20 ml, 2 Â ), the org. phase was dried (MgSO4), the solvent was evaporated, and the crude
products were purified by crystallization.
3-Chloro-3-[(1,4,5-trimethyl-1H-imidazol-2-yl)disulfanyl]-2,2,4,4-tetramethylcyclobutanone (9a). Yield:
218 mg (65%). Yellowish crystals. M.p. 120 1228 (hexane/CH2Cl2). IR: 1791vs (CˆO), 1462m, 1381w,
1
1029w, 835w. H-NMR: 1.55 (s, 2 Me); 1.61 (s, 2 Me); 2.36, 2.37 (2s, 2 Me); 3.86 (s, MeN). 13C-NMR: 9.4, 12.6
(2q, 2 Me); 22.2, 23.1 (2q, 4 Me); 31.8 (q, MeN); 69.2 (s, C(2), C(4)); 86.5 (s, C(3)); 127.4, 135.4, 135.7 (3s, 3
.
‡
arom. C); 216.2 (s, C ˆ O). EI-MS: 332 (30, M ), 142 (57), 141 (100). Anal. calc. for C14H21ClN2OS2 (332.91): C
50.51, H 6.36, N 8.41; found: C51.09, H 6.45, N 7.90.
3-Chloro-3-[(1-cyclohexyl-4,5-diphenyl-1H-imidazol-2-yl)disulfanyl]-2,2,4,4-tetramethylcyclobutanone
(9b). Yield: 217 mg (41%). Yellowish crystals. M.p. 163 1658 (MeOH/CH2Cl2). IR: 2933vs, 2855s, 1789vs
(CˆO), 1444s, 1381m, 1325s, 1027m, 775s, 724vs. 1H-NMR: 0.90 1.77 (m, 10 H); 1.32 (s, 2 Me); 1.36 (s, 2 Me);
4.10 4.55 (m, 1 H); 6.98 7.38 (10 arom. CH). 13C-NMR: 22.5 (q, 2 Me); 23.0 (q, 2 Me); 25.0, 26.2, 33.1
(3t, 5 C H); 59.0 (d, CH); 69.3 (s, C(2), C(4)); 86.6 (s, C(3)); 126.4, 126.6, 127.8, 128.7, 129.1, 131.6 (6d, 10 arom.
2
.
‡
‡
CH); 127.8, 132.0, 133.9, 138.1, 139.8 (5s, 5 arom. C); 216.3 (s, CˆO). EI-MS: 525 (5, M ), 524 (17, [M À 1] ),

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334 (53), 275 (13), 252 (100), 193 (43), 165 (12), 156 (9), 86 (26). Anal. calc. for C29H33ClN2OS2 (525.18): C
66.32, H 6.33, N 5.33; found: C65.97, H 5.90, N 5.25.
3-[(1-Benzyl-4,5-diphenylimidazol-2-yl)disulfanyl]-3-chloro-2,2,4,4-tetramethylcyclobutanone (9c). Yield:
217 mg (41%). Yellowish crystals. M.p. 137 1398 (MeOH/CH2Cl2). IR: 1786vs (CˆO), 1603m, 1497s, 1443s,
1381s, 1352s, 1027s, 917m, 832m, 775s, 728s, 695vs. 1H-NMR: 1.35 (s, 2 Me); 1.43 (s, 2 Me); 5.25 (s, C H).
2
13C-NMR: 22.4 (q, 2 Me); 23.1 (q, 2 Me); 48.7 (t, C H); 69.3 (s, C(2), C(4)); 86.3 (s, C(3)); 126.3, 126.7, 127.6,
2
128.0, 128.6, 128.9, 129.1, 130.7 (8d, 15 arom. CH); 130.3, 132.5, 133.6, 136.7, 139.1, 140.1 (6s, 6 arom. C); 216.3
‡
(s, CˆO). EI-MS: 532 (27, [M À 1] ), 283 (21), 252 (9), 193 (35), 156 (11), 91 (100). Anal. calc. for
C30H29ClN2OS2 (533.14): C67.58, H 5.48, N 5.25; found: C67.47, H 5.44, N 5.58.
5. Reaction of Thiouracil (ˆ2,3-Dihydro-2-thioxopyrimidin-4(1H)-one; 10) with 3. To a stirred suspension
of 10 (192.0 mg, 1.5 mmol) and Et3N (152 mg, 1.5 mmol) in CH2Cl2 (1 ml) was added a soln. of freshly distilled 3
(218.0 mg, 1 mmol) in CH2Cl2 (2 ml) at r.t. When the addition was complete, stirring was continued for 20 min,
then CH2Cl2 (5 ml) was added, the soln. was washed with 2% HCl (10 ml) and H2O (10 ml, 2 Â ). The org. phase
was separated, dried (MgSO4), and evaporated. The crude product was purified by recrystallization.
2-[(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)disulfanyl]pyrimidin-4(3H)-one (11). Yield: 210 mg
(66%). Colorless crystals. M.p. 142 1448 (hexane/CH2Cl2). IR: 1790s (CˆO, ketone), 1690vs (CˆO,
1
pyrimidone), 1480s, 1430s, 1250s, 980m, 820s. H-NMR: 1.46 (s, 2 Me); 1.55 (s, 2 Me); 6.27, 7.80 (AB, J ˆ 7.95,
2 H). 13C-NMR: 22.2 (q, 2 Me); 23.6 (q, 2 Me); 69.6 (s, C (2'), C(4')); 87.2 (s, C (1')); 113.1, 153.8 (2d, C (5),
.
‡
C(6)); 161.0, 158.2 (2s, C(2), C(4)); 214.0 (s, CˆO). EI-MS: 318 (4, M ), 249 (16), 224 (29), 213 (100), 197
(24), 148 (11), 131 (66). Anal. calc. for C12H15ClN2O2S2 (318.85): C45.20, H 4.74, N 8.78; found: C44.77, H 4.62,
N 8.74.
6. Reaction of 12 with 3. A soln. of 12 (221 mg, 1 mmol) in CH2Cl2 (5 ml) was added to a stirred soln. of
freshly distilled 3 (227 mg, 1 mmol) in CH2Cl2 (5 ml). During the addition, the reaction flask was cooled in a
H2O/ice bath, then, the cooling bath was removed, and the mixture was stirred at r.t. After 24 h, the solvent was
evaporated, and the solid residue was separated by prep. TLC(SiO 2; hexane/Et2O 20 :1). Along with recovered
starting material 12 (92 mg, 42%), the oxo analogue 13 (54 mg, 26%) and a solid identified as 14 (22 mg, 7%)
were isolated as main fractions.
4,4-Dimethyl-2-phenyl-1,3-thiazol-5(4H)-one (13). Yield: 54 mg (26%). Yellowish oil. The 1H-NMR
spectrum of the isolated material was identical with that of an original sample of 12 [24].
5,5-Bis[1-chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)disulfanyl]-4,5-dihydro-4,4-dimethyl-2-phenyl-1,3-
thiazole (14). Yield: 22 mg (7%). Colorless crystals. M.p. 145 1478 (hexane). IR: 2977m, 1785vs (CˆO),
1447m, 1381m, 1260w, 949m, 835w, 767m. 1H-NMR: 1.39 (s, 2 Me); 1.41 (s, 2 Me); 1.43 (s, 2 Me); 1.49 (s, 2 Me);
1.60 (s, 2 Me); 7.38 7.47 (m, 3 arom. H); 7.83 7.86 (m, 2 arom. H). 13C-NMR: 22.2, 22.3, 22.9, 23.5, 24.0
(5q, 10 Me); 69.0, 69.7 (2s, 2 C(2'), 2 C(4')); 84.5, 85.5, 95.1 (3s, 2 C(1'), C(4), C(5)); 128.1, 128.4, 128.7 (3d, 5
arom. CH); 131.5 (s, 1 arom. C); 160.0 (s, CˆN); 216.0 (s, CˆO). Anal. calc. for C27H35Cl2NO2S5 (635.06): C
50.92, H 5.54, N 2.20; found: C50.04, H 5.43, N 2.01.
7. Reaction of 8b with 165). A soln. of freshly distilled 16 (52.0 mg, 0.20 mmol) in CH2Cl2 (0.5 ml) was added
dropwise to a stirred soln. of 8b (70 mg, 0.21 mmol) and Et3N (20 mg, 0.20 mmol) cooled in a H2O/ice bath. The
exothermic reaction was complete after 15 min. Then, the mixture was diluted with 10 ml CH2Cl2, extracted with
H2O (10 ml, 3 Â ), and the org. phase was dried (MgSO4). The solvent was evaporated, and the solid residue was
purified by crystallization.
3-Chloro-3-[(1-cyclohexyl-4,5-diphenyl-1H-imidazol-2-yl)trisulfanyl]-2,2,4,4-tetramethylcyclobutanone
(17). Yield: 79 mg (70%). Yellow crystals. M.p. 180 1828 (hexane/CH2Cl2). IR: 2933s, 1792vs (CˆO), 1444m,
1332w, 1027w, 825w, 776w, 699s. 1H-NMR: 0.75 1.90 (m, 10 H); 1.39 (s, 2 Me); 1.41 (s, 2 Me); 4.10 4.40
(m, 1 H); 7.04 7.42 (m, 10 arom. H). 13C-NMR: 22.9 (q, 2 Me); 23.6 (q, 2 Me); 25.2, 26.4, 33.6 (3t, 5 C H); 59.0
2
(d, CH); 69.6 (2s, C(2), C(4)); 88.3 (s, C(3)); 127.0, 127.2, 128.3, 129.2, 129.6 (5d, 10 arom. CH); 132.0, 132.8,
.
‡
‡
134.0, 139.5, 140.8 (5s, 5 arom. C); 216.2 (s, CˆO). EI-MS: 557 (<1, M ), 556 (4, [M À 1] ), 334 (100), 333
(32). Anal. calc. for C29H33ClN2OS3 (557.24): C62.51, H 5.97, N 5.03; found: C62.10, H 5.98, N 5.24.
8. Reaction of 10 with 16. To a stirred suspension of 10 (192 mg, 1.50 mmol) and Et3N (152 mg, 1.50 mmol)
in CH2Cl2 (1 ml) was added dropwise at r.t. a soln. of freshly distilled 16 (259 mg, 1.00 mmol) in CH2Cl2 (2 ml).
After 20 min stirring, CH2Cl2 (5 ml) was added, and the mixture was washed with 2% HCl (10 ml) and H2O
(10 ml, 2 Â ). The org. phase was dried (MgSO4) and evaporated to give a crystalline, colorless solid.
Crystallization of the crude product afforded an anal. pure sample.
5
¬
¬
Experiment performed by K. Tegos, University of Ëodz, 2002.
)

Helvetica Chimica Acta Vol. 86 (2003)
2281
2-[(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)trisulfanyl]pyrimidin-4(3H)-one (18). Yield: 230 mg
(65%). Colorless crystals. M.p. 169 1708 (hexane/CH2Cl2). IR: 3100 2614 (br., NH), 1790s (CˆO), 1683vs
(CˆO, pyrimidone), 1524s, 1448s, 1270s, 980s, 830m. 1H-NMR: 1.45 (s, 2 Me); 1.46 (s, 2 Me); 6.31, 7.90 (AB, J ˆ
6.6, 2 H). 13C-NMR: 22.5 (q, 2 Me); 23.4 (q, 2 Me); 69.4 (s, C (2'), C(4')); 112.8, 154.4 (2d, C(5), C(6)); 158.9,
‡
162.8 (2s, C(2), C(4)); 215.0 (s, CˆO). CI-MS (NH3): 253 (16), 251 (35, [M ‡ 1] ), 289 (15), 288 (13), 287
(100), 238 (8), 221 (10), 144 (15). Anal. calc. for C12H15ClN2O2S3 (350.91): C41.07, H 4.31, N 7.98, S 27.41; found
C40.95, H 4.40, N 7.95, S 27.53.
9. Reaction of 12 with 16. To a soln. of freshly distilled 16 (155 mg, 0.60 mmol) in CH2Cl2 (5 ml), which was
cooled in acetone/dry ice bath (À 788), was added dropwise a soln. of 12 (66 mg, 0.30 mmol) in CH2Cl2 (2 ml) at
À 788, and the mixture was stirred at this temp. for 6 h. After 24 h at r.t., the solvent was evaporated, and the
residue was separated by prep. TLC(SiO 2; hexane/Et2O 20 :1). Along with a small amount of recovered 12
(10 mg, 16%), 1,3-thiazolone 13 (47 mg, 78%) and pentasulfane 19 were obtained.
1,5-Bis(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl)pentasulfane (19). Yield: 112 mg (78%). Colorless
crystals. M.p. 136 1388 (hexane). IR: 2969m, 2867m, 1790vs (CˆO), 1460s, 1455s, 1379s, 1363s, 1245m, 1168s,
1
1134m, 1030s, 911s, 887s, 830m, 780m. H-NMR: 1.44 (s, 4 Me); 1.47 (s, 4 Me). 13C-NMR: 22.8 (q, 4 Me); 23.4
‡
(q, 4 Me); 69.2 (s, 4 Me2C); 87.1 (s, 2 C(1)); 215.4 (s, 2 CˆO). CI-MS: 285 (27, [C8H12OS5 ‡ 1] ), 284 (100,
‡
C8H12OS5 ), 267 (17), 266 (6). Anal. calc. for C16H24Cl2O2S5 (479.60): C40.07, H 5.04, S 33.43; found: C40.11, H
5.09, S 33.17.
10. X-Ray Crystal-Structure Determination of 11, 14, 17, and 18 (see Table and Figs. 1 3)6). All
measurements were performed on a Nonius KappaCCD diffractometer [25] with graphite-monochromated
MoKa radiation (l 0.71073 ä) and an OxfordCryosystems Cryostream 700 cooler. Data reduction was
performed with HKL Denzo and Scalepack [26]. The intensities were corrected for Lorentz and polarization
effects, and an absorption correction based on the multiscan method [27] was applied. Equivalent reflections
were merged, except that for 14, Friedel pairs were not merged. Data collection and refinement parameters are
given in the Table, and views of the molecules are shown in Figs. 1 3. Each structure was solved by direct
methods with SIR92 [28], which revealed the positions of all non-H-atoms. The non-H-atoms were refined
anisotropically. In the cases of 11 and 18, the amine H-atom was placed in the position indicated by a difference
electron density map, and its position was allowed to refine together with an isotropic displacement parameter.
All remaining H-atoms, as well as all H-atoms of 14 and 17, were placed in geometrically calculated positions
and refined with a riding model where each H-atom was assigned a fixed isotropic displacement parameter with
a value equal to 1.2Ueq of its parent C-atom (1.5Ueq for the Me groups). Refinement of each structure was
carried out on F2 by full-matrix least-squares procedures, which minimized the function Sw(Fo2 À F2c )2.
Corrections for secondary extinction were not applied. In the case of 11, one reflection, whose intensity was
considered to be an extreme outlier, was omitted from the final refinement. Two significant peaks of residual
electron density (1.52 and 1.40 e äÀ3; next peak is 0.36 e äÀ3) remain in the vicinity of O(1). These features
could not be rationalized, but may be the result of poor crystal quality, as it was necessary to cut a fragment from
a large brittle block. In the case of 14, there are two independent molecules in the asymmetric unit. The
molecules have very similar conformations, although molecule B is inverted with respect to molecule A. The
atomic coordinates of the two molecules were tested carefully for a relationship from a higher symmetry space
group with the program PLATON [29], but none could be found. Ten reflections, whose intensities were
considered to be extreme outliers, were omitted from the final refinement. Refinement of the absolute structure
parameter [30] yielded a value of 0.51(3), which indicates that the crystals are inversion twins. Neutral-atom-
scattering factors for non-H-atoms were taken from [31a], and the scattering factors for H-atoms were taken
from [32]. Anomalous dispersion effects were included in Fc [33]; the values for f ' and f '' were those of [31b].
The values of the mass attenuation coefficients are those of [31c]. All calculations were performed using the
SHELXL97 [34] program.
In 11, the NH group forms bifurcated H-bonds. One interaction is an intramolecular H-bond with the most
distant S(1)-atom of the molecule. This forms a five-membered loop with a graph set motif [35] of S(5). The
other interaction is an intermolecular H-bond with the cyclobutanone O(1)-atom of a neighboring molecule and
links the molecules into centrosymmetric dimeric units which have a graph set motif of R22(8). The NH group of
6
)
CCDC-200712 200714 and 203557 contain the supplementary crystallographic data for this paper. These
data can be obtained, free of charge, via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax:
‡441223336033; e-mail: deposit@ccdc.cam.ac.uk).

2282
Helvetica Chimica Acta Vol. 86 (2003)
Table. Crystallographic Data of 11, 14, 17, and 18
11
hexane/CH2Cl2 benzene
C12H15ClN2O2S2 C27H35Cl2NO2S5 C29H33ClN2OS3 C12H15ClN2O2S3
14
17
18
Crystallized from
hexane/CH2Cl2 hexane/CH2Cl2
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
]
318.83
636.78
557.23
350.89
colorless, prism colorless, prism yellow, needle
colorless, plate
Crystal dimensions [mm]
Temp. [K]
Crystal system
0.15 Â 0.20 Â 0.25 0.15 Â 0.20 Â 0.20 0.08 Â 0.13 Â 0.18 0.05 Â 0.22 Â 0.25
160(1)
160(1)
monoclinic
P21
160(1)
monoclinic
P21/c
160(1)
monoclinic
P21/c
triclinic
≈
Space group
P1
Z
2
4
4
4
Reflections for cell determination
2q Range for cell determination [8]
19095
72062
21410
46013
4 60
4
60
4
60
2
55
Unit cell parameters
a [ä]
b [ä]
c [ä]
a [8]
b [8]
7.9038(2)
8.0878(2)
12.2811(3)
99.5214(9)
98.9073(9)
100.922(1)
746.04(3)
1.419
11.4713(1)
23.5861(2)
12.5495(1)
90
114.1797(4)
90
3097.54(5)
1.365
0.572
28.3425(6)
11.2684(2)
8.5224(1)
90
93.5783(6)
90
2716.53 (8)
1.362
0.397
19.9472(3)
7.5302(1)
10.8067(2)
90
105.6430(8)
90
1563.11(4)
1.491
0.646
g [8]
V [ä3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
0.534
f and w
60
f and w
60
f and w
55
f and w
60
2q (max) [8]
Transmission factors (min; max)
Total reflections measured
0.842; 0.925
22598
0.874; 0.919
76350
0.883; 0.972
46572
0.848; 0.971
31233
>Symmetry independent reflections 4339
17916
6213
4548
Reflections with I > 2s (I)
Reflections used in refinement
Parameters refined
3360
4338
180
13899
17906
688
4115
6213
329
3835
4548
189
Final R(F) [I > 2s (I) reflections]
0.0476
0.1357
0.0715; 0.3563
1.070
0.0405
0.0915
0.0444; 0
1.025
0.0466
0.1262
0.0612; 0.3487
1.050
0.0327
0.0850
0.0411; 0.6041
1.056
wR(F2) (all data)
Weighting parameters [a; b]a)
Goodness-of-fit
Final Dmax /s
D1 (max; min) [e äÀ3
0.001
1.52; À 0.40
0.001
0.68; À 0.42
0.001
0.55; À 0.48
0.001
0.40; À 0.47
]
a) wÀ1 ˆ s 2(F2o ) ‡ (aP)2 ‡ bP where P ˆ (Fo2 ‡ 2F2c )/3
18 forms an intermolecular H-bond with the amide O-atom of a neighboring molecule and thereby links the
molecules into infinite chains, which run parallel to the y-axis and have a graph set motif of C(4).
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ReceivedFebruary 12, 2003