Novel synthesis and thermal ring fission of 7-aryl-1,2,3,4,5,7-pentathiazocanes

Article abstract of DOI:10.1246/cl.2002.90

Treatment of 1,5,3,7-dithiadiazocanes 1 with bromine-elemental sulfur or disulfur dichloride (S₂Cl₂) afforded 1,2,3,4,5,7-pentathiazocanes 3, and heating of 3 caused unusual thermal ring fission to give an inseparable mixture of polysulfide chains bearing a thioformamide moiety on each terminal.

Full text of DOI:10.1246/cl.2002.90

90
Chemistry Letters 2002
Novel Synthesis and Thermal Ring Fission of 7-Aryl-1,2,3,4,5,7-pentathiazocanes
Kazuaki Shimada, Takamasa Yoshida, Kenshiro Makino, Tatsuya Otsuka, Yuki Onuma, Shigenobu Aoyagi, Yuji Takikawa,ꢀ
and Chizuko Kabutoy
Department of Chemical Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551
y
Instrumental Analysis Center for Chemistry, Graduate School of Science, Tohoku University, Sendai, Miyagi 980-8578
(Received October 11, 2001; CL-010997)
Treatment of 1,5,3,7-dithiadiazocanes 1 with bromine-
crown-type polysulfide ring system,5;7 and the conformational
feature of 3a showed a similarity to those of the reported eight-
membered cyclic polysulfides, such as 1c, S8, S8O, and
heptathiaphosphocanes.
elemental sulfur or disulfur dichloride (S2Cl2Þ afforded
1,2,3,4,5,7-pentathiazocanes 3, and heating of 3 caused unusual
thermal ring fission to give an inseparable mixture of polysulfide
chains bearing a thioformamide moiety on each terminal.
Table 1. Synthesis of 1,2,3,4,5,7-Pentathiazocanes 3
Syntheses of macrocyclic polysulfides are of great interest in
the light of their structures, reactivities, and synthetic applica-
tions. However, in spite of the potentiality concerning the
practical uses for antibacterial drugs, natural flavors, or as
industrial vulcanizing agents, only limited studies on medium-
sized cyclic polysulfides havebeen achieved dueto their difficulty
for preparation and their lability toward various reagents.1 During
our studies on cyclic polychalcogenoacetals, we reported an
oxidative ring contraction of 1,5,3,7-dichalcogenadiazocanes A
(X ¼ Se, Te) to give 1,2,4-dichalcogenazolanes C (X ¼ Se, Te)
via dications B,2 and it was naturally expected that a similar
oxidation of sulfur analogues A (X ¼ S) would afford macro-
cyclic polysulfides via strained 1,2,4-dithiazolanes C (X ¼ S).3
Along with such assumption, we attempted oxidation of A
(X ¼ S), and in this paper we would like to describe a novel
synthesis of 1,2,3,4,5,7-pentathiazocanes 3. An unusual thermal
ring fission of D is also reported in this paper.
1
The H NMR monitoring of the reaction of 1a with S2Cl2
(1.5 mol amt.) in an NMR tube at À50 ꢁC in CD2Cl2 showed two
pairs of AB-type doublets (ꢀ ¼ 5:11 and 5.16 ppm, and ꢀ ¼ 5:79
and 5.82 ppm) and a sole sharp singlet (ꢀ ¼ 5:68 ppm), and the
former signals gradually disappeared along with the raising up of
the temperature. In contrast, the latter remained unchanged even
1,5,3,7-Dithiadiazocanes 1a-d were prepared according to
the reported methods.2;4;5 Subsequently, treatment of a CH2Cl2
solution of 1 with Br2 (1.1 mol amt.) at À78 ꢁC afforded trace
amounts of 1,3,5-thiadiazixanes 46 and insoluble products 5along
with unexpected 1,2,3,4,5,7-pentathiazocanes 3 in low yields.
Yields of 3 were dramatically improved by treating 1 with Br2–S8
or S2Cl2. However, the optimized amount of S2Cl2 for the
reactions was 1.5 mol amt. for 1, and the use of more than 2.0
molar amount of S2Cl2 mainly afforded 5. In all cases, 1,2,4-
dithiazolanes 2 were not found in the crude products.2f;2g
Independent treatment of 1a with BF3ÁOEt2 (0.2 mol amt.) in
CH3CN also afforded the same ring contraction product 4a(22%)
along with 5-phenyl-1,3,5-dithiazixane (35%). These results
indicated that 4 were given through acid-induced ring fission and
recombination of 1. All results of synthesis of 3 through oxidation
of 1 are summarized in Table 1. Structural determination of 3a
was achieved by X-ray analysis, and the ORTEP drawing of 3a is
shown in Figure . The X-Ray data exhibited that 3a possessed a
when the measuring temperature was raised up till 25 ꢁC. The 13
C
NMR monitoring also showed the similar results. The three
methylene signals (ꢀ ¼ 63:9, 71.5, and 68.5 ppm) were initially
observed and only the last signal remained unchanged at a higher
temperature. The significant downfield shifts of the methylene
signals of the NMR spectra of the reaction mixture from those of
starting 1a suggested that the initially-formed species was a cyclic
sulfonium ion and the thermally-stable secondary species was
assumed to be a symmetrical dithia dication B (X ¼ S). It was
noteworthy that the signals of 3a or 4a were not observed at all
throughout the NMR monitoring. These results suggested that 3
were given from 1 through a plausible route involving oxidative
transannular S-S bond formation to form B (X ¼ S) and the
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
91
subsequent removal of the half part of B by the attack of some
nucleophiles during the usual workup process. Especially, 3
should be formed mainly as the less-strained eight-membered
cyclic polysulfides through thermal equilibration of the reaction
mixture involving elemental sulfur.
Compounds 3 were unreactive toward aerobic exposure and
oxidizing agents (mCPBA, aq. H2O2 solution, or CH3CO3H). In
contrast, treatment of 3 with nucleophiles (propylamine, NaCN,
or PPh3Þ or reducing agents (NaBH4 or LiAlH4) gave a complex
mixture, and treating a CH2Cl2 solution of 3 with HCl (gas,
excess) or BF3ÁOEt2 (1.0 mol amt.) afforded insoluble solids.
Treatment of 3a with S2Cl2 (1.0 mol amt.) from À78 ꢁC to R.T.
also gave polymeric product 5a and elemental sulfur.
Heating of a benzene solution of 3 at refluxing temperature in
the presence or absence of Et3N (excess) gave the recovery of 3.
However, 3 was converted into inseparable mixtures of
polysulfides 6 (x ¼ 1, 2, and 3) by heating in toluene at refluxing
temperature. The mass spectra of 6 revealed the parent ion peaks
of each components, and the 1H NMR spectra of 6 showed several
signals of the thioformyl protons and the methylene protons at
ꢀ ¼ 9:50{9:60 and ꢀ ¼ 5:20{5:50 ppm, respectively. The 13C
NMR spectra of 6 also exhibited the corresponding signals of the
thioformyl carbons and the methylene carbons at ꢀ ¼ 189{190
and ꢀ ¼ 58{60 ppm, respectively. From the MS data and the
elemental analysis data of 6, the average values of x for 6 were
approximately estimated to be 1.5 in all cases. Especially,
trisulfide 6a (x ¼ 1, 8%) was obtained after chromatographic
separation. In addition, the mixture of 6a (x ¼ 1:5 approximately)
was converted into a mixture of bisformamides 7a (x ¼ 0 and 1,
about 1 : 1) by aerobic exposure for 2 weeks, and the LiAlH4
reduction of the mixture of 7a in THF followed by treating CH3I
afforded 8a in 61% yield. Results of the thermal reactions of 3 are
given in Table 2.
N-CHS) among the signals of 6 and unidentified complex signals
along with gradual decreasing of 3a. This result indicated that
thermal ringfission of 3 afforded thiols 9 and the reaction of 9 with
elemental sulfur would give polysulfides 6. It was suggested that 9
were given by thermal ring fission from 3 directly or, more
probably, from 2 which might be generated through thermal
sulfur extrusion of 3. However, all attempts for isolation or
trapping of 2 or thiol 9a using phenylacetylene, DMAD, or CH3I
were not successful.
In conclusion, we found a synthesis and thermal ring fission
of 1,2,3,4,5,7-pentathiazocanes 3. Further mechanistic inspection
for the formation of 3 from 1 are under way in our laboratory.
This work was partially supported by Grant-in-Aid for
Scientific Research (No. 12650843) from the Ministry of
Education, Science, Sports, and Culture.
References and Notes
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Table 2. Thermal Reaction of 1,2,3,4,5,7-Pentathiazocanes 3
3
4
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The X-ray crystallographic data of 3a (R ¼ C6H5): C8H9NS5,
Mw ¼ 279:47, Colorless Prism, Monoclinic, P21/c(No. 14), a ¼
ꢁ
ꢂ
13:533ð3Þ, b ¼ 4:7633ð9Þ, c ¼ 19:485ð3Þ A, ꢁ ¼ 110:15ð1Þ , V ¼
1179:1ð4Þ A , Z ¼ 4, Dcalc ¼ 1:574 g/cm3, ꢂðCuK Þ ¼ 87:29 cmÀ1
,
ꢂ 3
ꢃ
R ¼ 0:065, Rw ¼ 0:067.
8
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Scheme 1.
1
The H NMR monitoring of the thermal reaction of 3a in
C6D6 at 108 ꢁC in an NMR tube showed the signals assigned to
thiol 9a (ꢀ ¼ 3:28 ppm (1H, t, J ¼ 8:9 Hz) and ꢀ ¼ 4:71 ppm
(2H, d, J ¼ 8:9 Hz) for N-CH2-SH, and ꢀ ¼ 9:10 ppm (1H, s) for