Sulfenyl halides in the synthesis of heterocycles. 4. Heterocyclization in reactions of alkenes with sulfenylating reagents based on di(2-pyridyl) disulfide

Article abstract of DOI:10.1007/s10593-012-1104-1

Sulfenylating reagents have been obtained by the action of sulfuryl chloride or antimony pentachloride on di(2-pyridyl) disulfide. Their interaction with alkenes proceeds as addition-cyclization with ring closure by the nitrogen atom of the pyridine fragment of the sulfur-containing electrophile with the formation of 2,3-dihydro[1,3]thiazolo[3,2-a]pyridinium derivatives.

Full text of DOI:10.1007/s10593-012-1104-1

Chemistry of Heterocyclic Compounds, Vol. 48, No. 7, October, 2012 (Russian Original Vol. 48, No. 7, July, 2012)
SULFENYL HALIDES IN THE SYNTHESIS OF
HETEROCYCLES. 4*. HETEROCYCLIZATION
IN REACTIONS OF ALKENES WITH SULFENYLATING
REAGENTS BASED ON DI(2-PYRIDYL) DISULFIDE
A. V. Borisov1**, Zh. V. Matsulevich1, V. K. Osmanov1, G. N. Borisova1,
G. Z. Mammadova2, A. M. Maharramov 2, and V. N. Khrustalev3
Sulfenylating reagents have been obtained by the action of sulfuryl chloride or antimony pentachloride
on di(2-pyridyl) disulfide. Their interaction with alkenes proceeds as addition-cyclization with ring
closure by the nitrogen atom of the pyridine fragment of the sulfur-containing electrophile with the
formation of 2,3-dihydro[1,3]thiazolo[3,2-a]pyridinium derivatives.
Keywords: alkenes, di(2-pyridyl) disulfide, sulfenyl chlorides, heterocyclization.
In recent years, we have formed an approach to the synthesis of chalcogen-, nitrogen-containing
heterocycles based on the cyclization in AdE reactions of unsaturated compounds with chalcogen-centred
electrophiles, which proceeds with ring closure by the nitrogen atom contained in the molecule of the starting
reactant [1-6].
In the development of the proposed approach, di(2-pyridyl) disulfide (1) has been used in the present
work as a potential precursor of new sulfur-containing electrophiles suitable for effecting tandem addition-
cyclization processes. It is known that by chlorine or sulfuryl chloride treatment of disulfide 1, the
corresponding sulfenyl chloride is formed [7, 8]. As far as we know, reactions of this rather unstable sulfenyl
chloride with unsaturated compounds have not been studied previously, and therefore such an investigation
seems of interest. As we demonstrated, reagents useful for the above-mentioned type of heterocyclization are
generated by the action of antimony pentachloride on di(2-pyridyl) diselenide and its tellurium-containing
analog [9, 10]. This procedure is also demonstrated for disulfide 1 in the present work.
_______
*For Communication 3, see [1].
_______
**To whom correspondence should be addressed, e-mail: avb1955@rambler.ru.
1
R. E. Aleeksev Nizhny Novgorod State Technical University, 24 Minina St., Nizhny Novgorod 603950,
Russia.
2Baku State University, 23 Z. Khalilova St., Baku A3-1148, Azerbaijan; e-mail: bsu@bsu.az.
3A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova St.,
Moscow 119991, Russia; e-mail: vkh@xray.ineos.ac.ru.
_________________________________________________________________________________________
Translated from Chemistry of Heterocyclic Compounds, No. 7, pp. 1180-1186, July, 2012. Original
article submitted September 23, 2011.
1098
0009-3122/12/4807-1098©2012 Springer Science+Business Media New York

We have established that by sequentially adding to a solution of disulfide 1 in methylene chloride at
20oC at first sulfuryl chloride and then styrene (2) or 3,4-dihydro-2H-pyran (3), 2,3-dihydro[1,3]thiazolo-
[3,2-a]pyridinium derivatives are formed, namely, the heterocycles 4a and 5a in yields of 93 and 97%,
respectively.
1) SO2Cl2
CH2Cl2
20°C
1) SO2Cl2
CH2Cl2
20°C
S
Ph
Cl
Cl
N+
N+
Ph
N
S
2)
S
2
2)
O
CH2
5a
1
4a
2
O
3
The sulphenylation of unsaturated compounds 2 and 3 under conditions when antimony pentachloride is
used to oxidize the disulfide 1 (methylene chloride, -40oC) also leads to the formation of cyclization products –
the salts 4b and 5b in yields of 86 and 88%, respectively.
1) SbCl5
CH2Cl2
–40°C
1) SbCl5
CH2Cl2
–40°C
S
Ph
N+
N+
1
2–
–
2) 2
SbCl52– · SbCl4
SbCl5
2) 3
2
S
4b
O
3
5b
1
The structures of the compounds synthesized were confirmed by methods of IR and H NMR
spectroscopy, elemental analysis data, and also X-ray structural analysis for the salts 4b and 5b (Figs. 1 and 2).
Fig. 1. Crystal structure of compound 4b with atoms represented by thermal vibration ellipsoids of 50%
probability. The alternative position of the disordered chlorine atom is shown by the bold dotted line.
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2-
2-
-
Compounds 4b and 5b are salts containing pyridinium cations with SbCl5 and SbCl5 ·SbCl4 anions,
respectively. Compound 4b is isostructural with the selenium analog recently studied by us [9]. The five-
membered heterocyclic cation in the molecule of 4b assumes an "envelope" type conformation with the carbon
atom C(7) deviating by 0.552(4) Å from the plane formed by the remaining ring atoms. The bulky phenyl
substituent occupies a less sterically favorable axial position, which is determined by the direction of addition of
the sulphenylating reagent to styrene. The SbCl52- anions in compound 4b take up a slightly twisted tetragonal-
pyramidal configuration (the range of valence angle Cl–Sb–Cl values is 86.87(3) to 93.13(3)o). The equatorial
bond lengths between the antimony atom and the chlorine atoms located at the base of the pyramid (mean value
2.6014(7) Å) significantly exceed the length of the axial bond of the antimony atom with the chlorine atom
2-
located at its apex (2.3037(13) Å). A similar structure is characteristic of an isolated SbCl5 anion [9, 11-14]
and is explained by the effect of the stereochemically active lone electron pair of the antimony(III) atom
occupying a trans position relative to the short (axial) Sb–Cl bond and complementing the environment of the
antimony(III) atom to octahedral.
Fig. 2. Crystal structure of compound 5b with atoms represented by thermal vibration ellipsoids of 50%
probability without showing solvate molecules of methylene chloride and hydrogen atoms. The alternative
position of the disordered fragment of one of the cations (S*,S* diastereomer) is shown by the bold dotted lines.
The short Sb…Cl contacts between SbCl52- and SbCl4 anions are shown by the fine dotted lines.
-
1100

The cation of compound 4b has an asymmetric carbon atom C(6). The crystal of compound 4b is a
racemate. The cations and anions in structure 4b are packed in stacks.
The crystal of compound 5b contains three crystallographically independent pyridinium cations having
close geometry. The five-membered heterocycles of these cations take up an "envelope" conformation with
deviation of the carbon atoms C(10), C(20) [C(20')], and C(30) from the planes formed by the remaining ring
atoms of 0.585(4), 0.561(4), [0.439(5)], and 0.579(4) Å, respectively. The pyran rings have an almost ideal
2-
-
2-
-
"chair" conformation. Anions SbCl5 and SbCl4 in compound 5b form a complex anion SbCl5 ·SbCl4 by
means of Sb(1)…Cl(9) (3.2476(7) Å), Sb(2)…Cl(2) (3.0277(8) Å), and Sb(2)…Cl(5) (3.0400(7) Å) interactions,
which results in a strongly twisted octahedral coordination (Fig. 2). The bond lengths of the antimony atoms
with the chlorine μ2-bridge atoms (Cl(2), Cl(5), and Cl(9)) significantly exceed the lengths of the remaining
(terminal) Sb–Cl bonds, There are no short contacts between the sulfur atoms of the cations and the chlorine
-
atoms of the complex anions. The characteristic structure of the SbCl52- anions (tetragonal pyramid) and SbCl4
("swing") together with the fairly long Sb…Cl distances between them (greater than 3.0 Å) enables consideration
of a complex anion in the form of SbCl5 ·SbCl4 and not as Sb2Cl93- [15]. Today it represents the sole example
2-
-
of an anion of a similar type.
The cations of compound 5b have two asymmetric carbon atoms C(6) [C(16), C(26)] and C(10) [C(20)
(C(20')), C(30)] and potentially may form 4 diastereomers. The crystal of compound 5b is a racemate. It is
interesting to note, however, that in the crystal the enantiomeric pair of (S,R) and (R,S) diastereomers is
predominant, while the formation of the enantiomeric pair of (S,S) and (R,R) diastereoisomers is insignificant
(ratio of the respective enantiomeric pairs was equal to 2.8:0.2). The cations and complex anions in the structure
5b are packed in stacks.
Drawing conclusions from the results of the present study and data obtained by us previously [9, 10],
the probable scheme of formation of the heterocyclization products is as follows. Apparently by the action on
disulfide 1 of either sulfuryl chloride and antimony pentachloride, which may serve as a chlorinating agent
[6-21], 2-pyridine sulfenyl chloride (6) is generated. Further, depending on the reaction conditions, either
sulfenyl chloride 6 directly or its antimony(III) chloride complexes of type 7 and 8 act as sulfenylating reagents
towards unsaturated compounds.
SO2Cl2
CH2Cl2
N
SCl
6
1
SbCl5
(PyS+)2SbCl5
+
PyS+SbCl4
2–
–
6
+
SbCl3
CH2Cl2
7
8
We have therefore developed an efficient and convenient procedure for the synthesis of 2,3-di-
hydro[1,3]thiazolo[3,2-a]pyridinium derivatives based on the interaction of alkenes with sulfenylating reagents
generated by the action of sulfuryl chloride or antimony pentachloride on di(2-pyridyl) disulfide.
EXPERIMENTAL
The IR spectra were recorded on a Shimadzu IR Prestige-21 spectrometer in KBr pellets. The 1H NMR
spectra were obtained on a Bruker AM-300 (300 MHz) instrument in DMSO-d6, internal standard was TMS.
Elemental analysis was carried out on a Carlo Erba EA1108 CHNS-O automatic analyzer. Melting points of the
obtained compounds were determined on a Boetius hot stage apparatus.
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TABLE 1. Main Crystallographic Data and Refinement Parameters for
Compounds 4b and 5b
Parameter
Empirical formula
4b
5b · 2CH2Cl2
C26H24Cl5N2S2Sb
727.59
C32H40Cl13N3O3S3Sb2
Molecular mass, M
1315.20
100
T, K
100
Crystal type
Monoclinic
P21/n
Triclinic
P-1
Space group
Unit cell parameters
a, Å
6.6857(3)
12.1709(6)
17.2833(8)
90
9.6380(3)
10.8230(3)
23.5605(7)
97.690(1)
98.885(1)
91.002(1)
2404.49(12)
2
b, Å
c, Å
, deg.
, deg.
92.062(1)
90
, deg.
V, Å3
1405.45(11)
2
Z
dcalc, g·cm-3
1.719
1.817
F(000)
, mm-1
724
1296
1.626
2.013
2max, deg.
56
56
Number of reflections measured
Number of independent reflections
15186
3366
26946
11583
Number of reflections with I > 2σ(I) 2751
10049
Number of refined parameters
R1 (I > 2(I))
wR2 (all data)
GOОF
169
496
0.0319
0.0716
1.003
0.0376
0.0950
1.007
Tmin; Tmax
0.641; 0.758
0.689; 0.824
Reaction of Di(2-Pyridyl) Disulfide (1) – SO2Cl2 System with Unsaturated Compounds 2, 3
(General Method). A solution of SO2Cl2 (0.07 g, 0.5 mmol) in CH2Cl2 (10 ml) was added with stirring to a
solution of disulfide 1 (0.11 g, 0.5 mmol) in abs. CH2Cl2 (10 ml) at 20oC. The bright-yellow reaction mixture
was stirred for 15 min, then a solution of unsaturated compound 2 or 3 (1 mmol) in CH2Cl2 (5 ml) was added
dropwise. After 15 min, the solvent was evaporated in vacuum. Compounds 4a and 5a were obtained after
recrystallization of the residue from CH2Cl2.
3-Phenyl-2,3-dihydro[1,3]thiazolo[3,2-a]pyridin-4-ium Chloride (4a). Yield 0.23 g (93%); mp 209-
211oC. IR spectrum, , cm-1: 1607 (C=N). 1H NMR spectrum, δ, ppm (J, Hz): 8.47 (1H, d, 3J = 5.9, H-5); 8.40
3
3
3
3
3
(1H, dd, J = 8.8, J = 7.3, H-7); 8.28 (1H, d, J = 8.8, H-8); 7.69 (1H, dd, J = 7.3, J = 5.9, H-6); 7.59-7.32
3
3
2
3
(5H, m, H Ph); 6.60 (1H, dd, J = 8.3, J = 7.3, H-3); 4.35 (1H, dd, J = 11.7, J = 8.3) and 3.89 (1H, dd,
2J = 11.7, J = 7.3, 2-CH2). Found, %: C 62.31; H 4.72; N 5.45. C13H12ClNS. Calculated, %: C 62.52; H 4.84;
3
N 5.61.
cis-3,4,4a,10a-Tetrahydro-2H-pyrano[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-10-ium Chloride (5a).
Yield 0.22 g (97%); mp 103-105oC. IR spectrum, , cm-1: 1605 (C=N). 1H NMR spectrum, δ, ppm (J, Hz): 8.91
(1H, d, 3J = 5.9, H-9); 8.45 (1H, dd, 3J = 8.8, 3J = 7.3, H-7); 8.25 (1H, d, 3J = 7.3, H-6); 7.84 (1H, dd, 3J = 7.3,
3J = 5.9, H-8); 6.54 (1H, d, 3J = 5.9, H-10a); 4.52-4.40 (1H, m, H-4a); 3.95-3.87 (1H, m) and 3.80-3.69 (1H, m,
2-CH2); 2.27-2.19 (1H, m) and 1.98-1.87 (1H, m, 4-CH2); 1.78-1.63 (2H, m, 3-CH2). Found, %: C 52.11;
H 5.21; N 6.01. C10H12ClNOS. Calculated, % : C 52.28; H 5.27; N 6.10.
Reaction of Di(2-pyridyl) Disulfide (1) – SbCl5 System with Unsaturated Compounds 2, 3
(General Method). A solution of SbCl5 (0.15 g, 0.5 mmol) in CH2Cl2 (10 ml) was added with stirring to a
solution of disulfide 1 (0.11 g, 0.5 mmol) in abs. CH2Cl2 (10 ml) at -40oC under an atmosphere of dry Ar. The
1102

coloress reaction mixture was stirred for 15 min, then a solution of the unsaturated compound 2 or 3 (1 mmol) in
CH2Cl2 (5 ml) was added dropwise. The mixture was heated to room temperature, about 70% of the solvent was
evaporated in vacuum, and the mixture was left for 4-6 h. The precipitated white crystals of compounds 4b and
5b were separated by filtration.
Bis(3-phenyl-2,3-dihydro[1,3]thiazolo[3,2-a]pyridin-4-ium Pentachloroantimonate(III) (4b). Yield
1
0.31 g (86%); mp 240-241oC. IR spectrum, , cm-1: 1603 (C=N). H NMR spectrum was identical to the
spectrum of compound 4a. Found, %: C 42.87; H 3.25; N 3.79. C26H24Cl5N2S2Sb. Calculated, %: C 42.92;
H 3.32; N 3.85.
Crystal Solvate of Tris-(3,4,4a,10a-tetrahydro-2H-pyrano[2',3':4,5][1,3]thiazolo[3,2-a]pyridin-
10-ium Pentachloroantimonate(III)-tetrachloroantimonate(III) ·2CH2Cl2 (5b). Yield 0.29 g (88%); mp
1
102-103oC. IR spectrum, , cm-1: 1605 (C=N). H NMR spectrum was identical to the spectrum of compound
5a. Found, %: C 29.09; H 3.02; N 3.12. C32H40Cl13N3O3S3Sb2. Calculated, %: C 29.22; H 3.07; N 3.19.
X-ray Structural Investigation of Compounds 4b and 5b. The parameters of the unit cells and the
intensities of the reflections for compounds 4b and 5b were measured on a Bruker APEX-II CCD three-circle
diffractometer with a two-coordinate detector (T 100 K, λMoKα radiation, graphite monochromator, - and
ω-scanning). The main crystal structure data are given in Table 1.
Complete tables of atomic coordinates, bond lengths, valence angles, and anisotropic temperature
parameters for compounds 4b and 5b have been deposited at the Cambridge Crystallographic Data Center
(depositions CCDC 832558 and CCDC 832557, respectively).
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