Preparation and properties of nitrogen-substituted thiosulfinyl compounds and related new heterocycles

Article abstract of DOI:10.1016/j.tetlet.2007.09.127

The reaction of dilithiated N,N′-dimethyl-1,2-diphenylethylenediamine with disulfur dichloride (S₂Cl₂) gave a thiosulfinyl compound (R₂N)₂S{double bond, long}S, 2,5-dimethyl-3,4-diphenyl-1,2,5-thiadiazolidine 1-sulfide, whereas the treatment of dilithiated N,N′-bis(p-toluenesulfonyl)-1,2-diphenylethylenediamine with S₂Cl₂ furnished a new heterocycle, 3,6-bis(p-toluenesulfonyl)-4,5-diphenyl-4H,5H-1,2,3,6-dithiadiazine.

Full text of DOI:10.1016/j.tetlet.2007.09.127

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Tetrahedron Letters 48 (2007) 8116–8119
Preparation and properties of nitrogen-substituted
thiosulfinyl compounds and related new heterocycles
Sanae Yoshida, Yoshiaki Sugihara and Juzo Nakayama*
Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Sakura-ku, Saitama,
Saitama 338-8570, Japan
Received 27 August 2007; revised 19 September 2007; accepted 20 September 2007
Available online 22 September 2007
Abstract—The reaction of dilithiated N,N0-dimethyl-1,2-diphenylethylenediamine with disulfur dichloride (S2Cl2) gave a thiosulfinyl
compound (R2N)2S@S, 2,5-dimethyl-3,4-diphenyl-1,2,5-thiadiazolidine 1-sulfide, whereas the treatment of dilithiated N,N0-bis(p-
toluenesulfonyl)-1,2-diphenylethylenediamine with S2Cl2 furnished a new heterocycle, 3,6-bis(p-toluenesulfonyl)-4,5-diphenyl-
4H,5H-1,2,3,6-dithiadiazine.
Ó 2007 Elsevier Ltd. All rights reserved.
The chemistry of the thiosulfinyl (˜S@S) group has been
attracting considerable attention. Compounds that pos-
sess this highly reactive functional group become stable
to be isolated, only when both substituents on the sulfur
atom are heteroatom. Thus, F2S@S is a long-known
compound1 and the first synthesis of thionosulfites
(RO)2S@S was reported in 1965.2 Recently, new thiono-
sulfites have been synthesized and characterized in detail
by Harpp et al.3 We have also reported the preparation
of stable, crystalline thionosulfite 1 and the full charac-
terization of its chemical properties; it was obtained by
the treatment of cyclic diol 2 with 3 (Scheme 1).4
3 is.5 Thus, initially we have examined the reactions of
1,2-diamine 66 with 4 and 5 with the expectation of
obtaining 1,2,5-thiadiazolidine 1-sulfide 7a. However,
disappointingly, the reaction did not give the expected
7a, but gave sulfoxide 8 instead in 35% yield by the
use of 4 and in 93% yield by the use of 5 (Scheme 2).
The formation of 8 might involve the initial formation
of 9, which further reacts with 4 or 5 to give 7a whose
oxidation or hydrolysis leads to 8. Direct oxidation of
9 may also explain the formation of 8. Structure of 8
was established by independent synthesis; the reaction
of 6 with thionyl chloride gave 8 quantitatively.
As an extension of the above work, we have now inves-
tigated the preparation of nitrogen-substituted thio-
sulfinyl compounds (R2N)2S@S. Reportedly, 4 and 5,
easily obtainable from commercially available starting
materials, are more reactive sulfuration reagents than
We then examined the reaction of dilithiated 6 with
disulfur dichloride (ClSSCl), where the formation of
7a (via paths a and b in Scheme 3) and also the forma-
tion of a new heterocycle, 1,2-dithiadiazine 7b (path c)
were expected. Thus, 6 was dilithiated by n-BuLi
(2 equiv) in Et2O and then treated with ClSSCl. The
reaction gave a mixture of 7a, 8, and the starting mate-
rial 6 in the ratio 43:23:33, which was estimated by the
analysis of 1H NMR of the crude reaction mixture.
Dithiadiazine 7b was not formed. The reaction in THF
gave the same compounds in the ratio 54:13:33. Inciden-
tally, neither 7a nor 8 was formed by the use of triethyl-
amine as the base. Density functional theory (DFT)
calculations (B3LYP/6-31G* level)7 predicted that 7a is
more stable than 7b by 3.3 kcal/mol.
Scheme 1.
Keywords: Thiosulfinyl compound; New heterocycle; Ethylenediamine;
Disulfur dichloride.
Compound 7a is unstable both thermally and kineti-
cally, and could not be isolated in pure form despite
many efforts. It turned to 8 partially by hydrolysis or
*
Corresponding author. Tel.: +81 48 858 3390; fax: +81 48 858
3700; e-mail: nakaj@post.saitama-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.127

S. Yoshida et al. / Tetrahedron Letters 48 (2007) 8116–8119
8117
Scheme 2.
4.45 with J = 9.6 Hz. For the 13C NMR spectra, the
methine carbons of 7a appeared at d 76.1 and 79.4,
chemical shifts similar to those of 8, d 75.0 and 78.7.
Although 7a quickly reacted with CH2Cl2 to give 10,
1,2-diamine 6 did not react with CH2Cl2 even when a
solution of 6 in CH2Cl2 was allowed to stand for more
than one month (Scheme 4). The terminal sulfur atom
of the ˜S@S group of 7a is negatively charged as
predicted by Mulliken population analysis (Fig. 2),7 and
thus the initial process of the above conversion might
involve the nucleophilic attack of the sulfur atom on
the carbon atom of CH2Cl2. Compound 10 was alterna-
tively prepared by acid-catalyzed condensation of 6 with
paraformaldehyde in CH2Cl2 for 19 h at room tempera-
ture, which gave a mixture of 6 and 10 in the ratio 69:31.
Next, the reaction of 1,2-ethylenediamine 11,9 which has
an electron-withdrawing group on the nitrogen atoms,
with ClSSCl was examined. Thus, 11 was treated with
n-BuLi (2 equiv) in Et2O at 0 °C and then with ClSSCl,
which furnished compound 12b with a new heterocyclic
system in 57% isolated yield with the recovery of 11 in
39% (Scheme 5). The reaction used THF as the solvent
gave sulfoxide 13 in 27% yield with recovery of 11 in
72%. The structure of 12b was determined based on
1H NMR, 13C NMR, Raman, and IR spectral data
and X-ray crystallographic analysis. Molecular structure
of 12b is shown in Figure 3. The six-membered ring of
Scheme 3.
oxidation during purification processes. It also reacted
with CH2Cl2 to give 108 when its solution in CH2Cl2
was allowed to stand (Scheme 3). Thus, the 1H and
13C NMR spectra of 7a were determined by using the
sample freshly purified by silica gel column chromato-
graphy and containing small amounts of compounds 8
and 10 as the impurity. The two methine protons of 8
appear as two doublets at d 4.14 and 4.44 with
J = 9.7 Hz. The signal at d 4.14 is assigned to the trans
proton to the ˜S@O group, and the latter to the cis
one (Fig. 1). The difference of the observed chemical
shifts is due to the diamagnetic anisotropy of the ˜S@O
group. The 1H NMR data of 7a are expected to be
similar to those of 8 since the diamagnetic anisotropy
of the ˜S@S group is similar to that of the ˜S@O group
as previously reported by us.4 Indeed, the two methine
protons of 7a appeared as two doublets at d 4.19 and
Scheme 4.
Figure 2. Mulliken population analysis of 7a at the B3LYP/6-31G*
level.
Figure 1. 1H NMR chemical shifts of 7a and 8.

8118
S. Yoshida et al. / Tetrahedron Letters 48 (2007) 8116–8119
12a was observed even when 12b was heated in toluene-
d8 at 120 °C for 48 h in a sealed NMR tube. When 12b
was heated in boiling o-dichlorobenzene for 24 h,
decomposition took place to give 11 in a yield of less
than 33%. Compound 12b was hydrolyzed to 11 in
98% yield by treatment with NaHCO3 in aqueous
THF for 24 h at room temperature.
Finally, 1,8-diaminonaphthalene 1413 was treated with
1
n-BuLi at 0 °C and then with ClSSCl in THF. A H
NMR analysis of the crude reaction mixture revealed
that the reaction gave a 35:18:47 mixture of 15, 16,
and 14 (Scheme 6). Compound 15 is susceptible to
oxidation and was converted to 16 partially during iso-
lation procedure. Thus the isolated yield of 15 became
10%, while the yield of 16 increased to 27% and the yield
of 14 remained unchanged. The reaction gave neither
17a nor 17b.
Scheme 5.
12b exists in a chair conformation. The two S–N bond
lengths of 12b are not equal to each other and are
˚
1.699 and 1.691 A, and are shorter than the usual S–
3
10
˚
N(sp ) bond length (1.765 A); a literature survey
revealed that the S–N bond lengths of compounds
As described, DFT calculations predicted that methyl
group on the nitrogen atoms stabilizes the ˜S@S form,
whereas p-toluenesulfonyl group stabilizes the isomeric
–S–S– form. We therefore carried out DFT calculations
on compounds 18–23 to show that the relative stability
of the ˜S@S form A and –S–S– form B depends upon
the electronic properties of the substituent on the nitro-
gen atoms (Table 1). However, although they provided
expected results for the combinations of 18 and 19 and
of 22 and 23, they did not for a combination of 20
and 21. Thus, both for compounds 18 and 19, which
˜N–S–S–N— are generally shorter than the usual S–
3
N(sp ) bond lengths.11 The S–S bond length (2.034 A)
˚
of 12b is a usual one, although, reportedly, the S–S bond
lengths of X–S–S–X (X = O, 1.972 A; F, 1.888 A) are
shorter than the usual S–S bond lengths.1,3d,12
˚
˚
DFT calculations (B3LYP/6-31G** level)7 predicted, on
the contrary to the case of 7, that 12b is more stable than
12a by 3.7 kcal/mol. No thermal isomerization of 12b to
Figure 3. ORTEP plot of the molecular structure of 12b. Relevant
˚
bond lengths [A]: S(1)–N(1), 1.699; S(1)–S(2), 2.034; S(2)–N(2), 1.691.
Scheme 6.
Table 1. DFT calculations on the relative stability of the ˜S@S form A and the –S–S– form B7
Electron-donating groups
A
B
Electron-withdrawing groups
A
B
Ph
Ph
Ph
Ph
Ph
N
Ph
Ph
N
Ph
N
N
R
N
N
R
R
N R
N R
R
R
R
S
S
S
S
S S
S S
18: R = p-Me2NC6H4
0 kcal/mol
+2.0 kcal/mol
19: R = p-O2NC6H4
0 kcal/mol
+1.4 kcal/mol
N
N
N
N
R
R
R
N
R
R
N
S S
N R
R
N R
S S
S
S
S
S
20: R = p-Me2NC6H4
22: R = Me
0 kcal/mol
0 kcal/mol
ꢀ7.9 kcal/mol
ꢀ1.7 kcal/mol
21: R = p-O2NC6H4
23: R = MeCO
0 kcal/mol
0 kcal/mol
ꢀ5.3 kcal/mol
ꢀ14.0 kcal/mol
DFT calculations (BLYP/6-31G** level).

S. Yoshida et al. / Tetrahedron Letters 48 (2007) 8116–8119
8119
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In conclusion, we have succeeded in the preparation of
nitrogen-substituted thiosulfinyl compound 7a and new
heterocycles such as 12b and 15.
Acknowledgments
This work was supported by
a
Grant-in-Aid
(#16350019) for Scientific Research from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. S.Y. thanks the Japanese Society for the Promo-
tion of Science for Young Scientists for a Research
Fellowship.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2007.
09.127.
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