Synthesis and structure of dipyrido-1,4-dithiins

Article abstract of DOI:10.3987/COM-05-10491

Synthesis, properties and reactions of two isomeric dipyrido-1,4-dithiins of the C_2h and C_2v symmetry are described. Their structure determination and identification are based on spectroscopic methods (¹H and ¹³C NMR, HETCOR, gHMBC and MS), physical properties (mp and R_f), the 1,4-dithiin ring opening reactions and finally X-Ray analysis. A very unusual type of the Smiles rearrangement (S→S, the pyridyl group migrates from one sulfur atom to another) during the 1,4-dithiin ring opening with sodium methanethiolate enabling isomerization of dithiin with the C_2h symmetry to dithiin with the C_2v symmetry is found.

Full text of DOI:10.3987/COM-05-10491

HETEROCYCLES, Vol. 65, No. 11, 2005
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HETEROCYCLES, Vol. 65, No. 11, 2005, pp. 2619 - 2634
Received, 23rd June, 2005, Accepted, 8th September, 2005, Published online, 13th September, 2005
SYNTHESIS AND STRUCTURE OF DIPYRIDO-1,4-DITHIINS#
Beata Morak,a Krystian Pluta,*,a Kinga Suwińska,b Mirosława Grymel,c
Céline Besnard,d Marc Schiltz,d Christian Kloc,e and Theo Siegriste
a Department of Organic Chemistry, The Medical University of Silesia,
Jagielloñska 4, 41-200 Sosnowiec, Poland. E-mail: pluta@slam.katowice.pl.
b
Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52,
01-224 Warsaw, Poland.
c
Department of Organic and Bioorganic Chemistry and Biotechnology, The
Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland.
d
Laboratoire de Cristallographie, Ecole Polytechnique Federale de Lausanne,
Dorigny, CH-1015 Lausanne, Switzerland
e
Bell Laboratories, Lucent Technologies, Mountain Avenue, Murray Hill, NJ
07974, USA
Abstract – Synthesis, properties and reactions of two isomeric dipyrido-1,4-dithi-
ins of the C2h and C2v symmetry are described. Their structure determination and
13
identification are based on spectroscopic methods (1H and C NMR, HETCOR,
gHMBC and MS), physical properties (mp and Rf), the 1,4-dithiin ring opening
reactions and finally X-Ray analysis. A very unusual type of the Smiles rearran-
gement (S→S, the pyridyl group migrates from one sulfur atom to another) during
the 1,4-dithiin ring opening with sodium methanethiolate enabling isomerization
of dithiin with the C2h symmetry to dithiin with the C2v symmetry is found.
INTRODUCTION
Diareno - and diheteroareno-1,4-dithiins are promising novel polyheterocyclic electron donors in the
search of the organic materials with interesting electronic, optoelectronic and magnetic properties.1-3 Our
group found four fused pentacyclic diquino-1,4-dithiins that are useful substrates for obtaining various so
far unknown quinoline derivatives of different types (disubstituted quinolines,4a,5 diquinolinyl sulfides,4b,5-8
quinobenzothiazines4c and their salts,4d thiazinodiquinolines and related heterocyclodiquinolines4e and
quinolinyl crown thioethers4f). In our previous paper9 we described synthesis of the unknown dipyrido-
1,4-dithiin (3) (systematic name: dipyrido[3,4-b;4’,3’-e][1,4]dithiin) together with isomeric dipyrido-1,4-

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HETEROCYCLES, Vol. 65, No. 11, 2005
dithiin (2) (systematic name: dipyrido[3,4-b;3’,4’-e][1,4]dithiin) in the reaction of 4-chloro-3-nitropyridi-
o
ne (1) with sodium sulfide in DMSO at 140-150 C for 10 h. The same reaction carried out in DMF led
mainly to novel dipyrido-1,4-thiazines (4) and (5)9 (Scheme 1).
Cl
S
NO2
Y
N
N
N
Na2S
+
N
DMSO or DMF
S
3
N
1
S
2, 4, 5
Y = S (2), NH (4),
3'-nitro-4'-pyridyl (5)
Scheme 1
Here, we report new synthetic methods of both dipyrido-1,4-dithiins (2) and (3), their structure determi-
nation and discrimination on the basis of the spectroscopical data, physical properties, chemical transfor-
mations and X-Ray analysis.
RESULTS AND DISCUSSION
Synthesis
In order to improve the yields of dipyrido-1,4-dithiins (2) and (3), we examined reactions of 4-chloro-3-
nitropyridine (1) with sulfur reagents (sodium hydrogensulfide, sodium sulfide, thiourea) in selected sol-
vents (methanol, ethanol, HMPT) but we obtained only products of the chloro substitution: 4-mercapto-3-
nitropyridine (6), 3,3’-dinitro-4,4’-dipyridinyl disulfide (7), 4-ethoxy-3-nitropyridine (8) and 4-dimethyl-
amino-3-nitropyridine (9) (as a result of the action of ethanol and HMPT). Attempts of cyclization of
compound (6) in MEDG (monomethyl ether of diethylene glycol) and sulfolane gave only disulfide (7).
Only the cyclization of sodium 3-nitro-4-pyridinethiolate (6A) carried out in DMSO at 160 oC gave dipy-
OC2H5
N
S
S
N
NO2
vii
i
NO2
O2N
S
S
7
N
N
iv
N
8
Cl
SNa
SH
ii
N
NO2
NO2
NO2
i
v
vi
2
+
iii
N
1
N
N
6
S
viii
N(CH3)2
N
6A
ix
NO2
S
N
S
N
3
N
9
NO2 O2N
10
Scheme 2 Reagents: i, NaSH, Na2S or thiourea, MeOH or EtOH; ii, Na2S, EtOH, autoclave; iii, Na2S, HMPT;
iv, MEDG or sulfolane; v, MeONa, MeOH; vi, DMSO, vii, DMSO, NaOH; viii, (6), DMF; ix, Na2S, DMSO.
rido-1,4-dithiins (2) and (3) in 28% and 21% yields. We also tried to transform disulfide (7) and sulfide

HETEROCYCLES, Vol. 65, No. 11, 2005
2621
(10) (obtained from compounds (1) and (6)) into dithiins (2) and (3), respectively. Whereas the reaction
of disulfide (7) with sodium hydroxide in DMSO at 160 oC gave both dithiins (2) and (3) in 28% and 28%
yields, the reaction of sulfide (10) with sodium sulfide to form only dithiin (3) failed (giving only
compound (6)) (Scheme 2).
The formation of both dipyridodithiins (2) and (3) from compound (1) can be explained by analogy to the
formation of substituted dipyridazodithiins.11,12 The reaction proceeds probably through active interme-
diates thiirene (A1) and 1,3-dipolar species (A2) and (A3) which dimerize per se or crossed to give dithiins
(2) and (3) respectively (Scheme 3).
S
Cl
SNa
S
NO2
S
NO2
N
A2
N
N
A3
N
A1
N
1
6A
dimerization
A2 + A2
A2 + A3
or A3 + A3
S
S
N
N
N
N
S
S
3
2
Scheme 3
We also re-examined the procedure of the synthesis of dipyrido-1,4-dithiin (2) from 4-chloro-3-aminopy-
ridine (11) via diazotization, substitution of the diazonium group by the xanthate group and hydrolysis of
the obtained ethyl 4-chloro-3-pyridinedithiocarbonate (12) followed by cyclization, originally described
by Krowicki and Nantka-Namirski,12 giving dithiin (2) in 35 % yield. As we assumed the cyclization
proceeds smoothly in aprotic solvents we changed boiling methanol into boiling DMF. In this way we
obtained not only dithiin (2) in 40% yield but also small amounts of dithiin (3), pyridodithiolethione (13)
and 3,4-diethylthiopyridine (14). We found dithiolethione (13) to be smoothly transformed into dithiin (2)
in 92% yield in DMF in the presence of potassium hydroxide (Scheme 4).
As the yield of dithiin (3) was still unsatisfactory we decided to isomerize dithiin (2) via the 1,4-dithiin
ring opening - ring closure reactions. In our previous papers8,13 we carried out isomerization of two
diquino-1,4-dithiins with the C2h symmetry (15) and (16) into diquino-1,4-dithiins with the C2v symmetry
(17) and (18). We found that the primary products of the 1,4-dithiin ring opening in dithiins (15) and (16)
with sodium methanethiolate, sodium salts of 3’-mercapto-4-methylthio-3,4’-diquinolinyl sulfide and of
3-mercapto-2’-methylthio-2,3’-diquinolinyl sulfide, underwent an unprecedented S→S type of the Smiles
rearrangement5,6 8,13 (the quinolinyl groups migrate from one sulfur atom to another) to sodium salts of 4’-
mercapto-4-methylthio-3,3’-diquinolinyl sulfide and of 2-mercapto-2’-methylthio-3,3’-diquinolinyl sulfi-

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HETEROCYCLES, Vol. 65, No. 11, 2005
S
KOH
DMF
Cl
S
Cl
S
NH2
1. NaNO2, H2SO4
2. C2H5OCSSK
SCSOC2H5
S
N
KOH
DMF
+
N
N
N
N
N
S
2
13
11
12
SC2H5
S
SC2H5
N
+
S
3
N
Scheme 4
14
de in the reaction conditions (DMSO at 20 oC, 70 oC and 140 oC, respectively) (Scheme 5). Similar to the
reactions of diquino-1,4-dithiins (15-18)5,6,8,13,14 the model reactions of dithiins (2) and (3) with sodium
o
methanethiolate in DMSO at 70 C followed by S-methylation with methyl iodide led to isomeric x,y-
dimethylthio-3,4’- and 3,3’-dipyridinyl sulfides (19) and (20) (x,y = 3’,4 and 4,4’, respectively) in 79%
o
yield. When the reaction of dithiin (2) was carried out at 170 C the S→S type of the Smiles rearrange-
ment was observed and after methylation 4,4’-dimethylthio-3,3’-dipyridinyl sulfide (20) was obtained.
In this case the primary product, sodium salt of 4-methylthio-3’-mercapto-3,4’-dipyridinyl sulfide (19A)
underwent the rearrangement into sodium salt of 4-methylthio-4’-mercapto-3,3’-dipyridinyl sulfide (20A).
The last sulfide heated instead of alkylation gave the 1,4-dithiin ring closure product, dithiin (3) in 50%
yield. Since the unrearranged dithiin (2) was also recoved in 32% the efficiency of the rearrange-ment
SCH3
S
S
N
N
CH3SNa
N
NaS
S
N
15
SNa
N
SCH3
S
S
-CH3SNa
N
N
N
N
N
S
16
NaS
S
N
S
N
CH3SNa
S
N
SCH3
17
S
S
-CH3SNa
S
N
N
N
SNa
CH3S
18
Scheme 5

HETEROCYCLES, Vol. 65, No. 11, 2005
2623
was 74% taking into account the converted dithiin (2) (Scheme 6). The reverse isomerization of dithiin
(3) to dithiin (2) was unsuccessful, dithiin (3) was isolated in 87% yield. The observed rearrange-ment is
very unusual because the nucleophilic attack of the thiolate anion occurs at the position 3 in the pyridine
ring, which is not susceptible as a rule for such attack. The more reactive position 2 remains unaffected. It
is worth noting that ab initio calculations15 of all dipyridinyl sulfides showed possibility of the Smiles
rearrangement for 2,2’-, 2,3’- and 2,4’-dipyridinyl sulfides and in fact, the rearrangement of the S→N
type was observed only for 2,2’- and 2,4’-isomers.16 Our findings are the first examples of the Smiles
rearrangement of 3,4’-dipyridinyl sulfide (the S→S type) observed during isomerization of dithi-in (2)
and of 4,4’-dipyridinyl sulfide (the S→N type) observed during synthesis of dipyrido-1,4-thiazines (4) and
(5).9
SCH3
SCH3
S
N
S
N
S
CH3I
CH3SNa
N
N
N
NaS
-CH SNa
CH3S
,
3
N
S
2
N
19
19A
SCH3
SNa
SCH3
SCH3
S
S
S
CH3SNa
N
CH3I
-CH SNa
,
3
S
3
N
N
N
N
20
20A
Scheme 6
X-Ray analysis
Figure1. ORTEP drawings of dipirido-1,4-dithiins (2) and (3).

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HETEROCYCLES, Vol. 65, No. 11, 2005
None of six isomeric dipyrido-1,4-dithiins has been X-Ray analyzed. Both isomeric dipyrido-1,4-dithiins
(2) and (3) have pairs of the identical 3,4-pyridinediyl units, therefore they are difficult to distinguish. A
problem in the determination of the correct structures of diazino-1,4-dithiins was put forward by some
authors.17-19 The structure of dithiin (2) was determined until now on the basis of calculated and experi-
mental dipole moment10 and via logical sequence of dimerization of the 4-pyridylthio radical resulted in
o
thermolysis of 4,4’-dipyridinyl disulfide at 250 C.20 Since spectroscopic evidences are indirect and sub-
tle, chemical ones sometimes dubious (with the regard to isomerization and rearrangement) only X-Ray
analysis as a direct proof can give a final answer regarding the structure determination. Crystals of both
dithiins for X-Ray analysis were grown from DMF, however, the crystals of dithiin (3) were twinned
what makes the analysis difficult. Moreover synchrotron radiation was used to overcome the weakness of
the difracted intensities. Similarly to dithiin (16),8 dithiin (3) crystallized also with two molecules in the
unit cell. This X-Ray study is the final confirmation of both compounds (2) and (3) as dipyrido[3,4-b;3’,4’-e]-
[1,4]dithiin and dipyrido[3,4-b;4’,3’-e][1,4]dithiin, respectively. In contrast to planar dipyrazo-1,4-dithi-
in21 both dipyrido-1,4-dithiins (2) and (3) are folded mainly along the S...S axis and additionally along the
C-C axes between the dithiin and pyridine rings (Figure 1). The central dithiin ring is in a boat conforma-
tion with the sulfur atoms deviating from the central CCCC plane. The 3-pyridinyl-sulfur bond is slightly
longer than the 4-pyridinyl-sulfur bond in the both dithiins. Table 1 contains selected geometrical features
of dithiins (2) and (3).
Table 1. Selected details of the molecular geometry of dithiins (2) and (3)
Geometrical feature
Dithiin (2)
Dithiin (3)
Molecule 1
Molecule 2
1.777(7), 1.769(7)
1.768(7), 1.755(8)
100.6(3), 100.6(3)
42.6(3)
3-pyridinyl-sulfur bond (Å)
4-pyridinyl-sulfur bond (Å)
CSC angle (o)
1.763(3)
1.757(3)
1.768(3), 1.765(7)
1.762(7), 1.755(8)
100.6(3), 100.9(3)
46.8(4)
101.41(14)
43.91(8)
Dihedral angle between the
pyridine rings (o)
Dihedral angle between the
halves of the dithiin ring (o)
Displacement of the sulfur
atoms from the cental plane (Å)
48.08(7)
0.607(2)
50.8(4)
48.8(4)
0.635(3)
0.647(3)
0.589(3)
0.641(3)
1H and 13C NMR spectral assignment dipyrido-1,4-dithiins (2) and (3).
1
13
The H and C NMR spectra of both dipyrido-1,4-dithiins (2) and (3) revealed the symmetry of dithiins
because the numbers of the proton and carbon signals were half the number of nuclei in the molecules.

HETEROCYCLES, Vol. 65, No. 11, 2005
2625
1
The H NMR spectra showed one singlet signal at δ = 8.58 ppm for dithiin (2) and at δ = 8.63 ppm for
dithiin (3) and two doublet signals with ortho coupling at δ = 7.39 ppm and δ = 8.45 ppm for dithiin (2),
and at δ = 7.38 ppm and δ = 8.46 ppm for dithiin (3), easy to assign on the basis of the 3- and 4-pyridyl
13
proton signals.22 The C NMR spectra showed three tertiary carbon signals and two quaternary carbon
signals. In order to assign unquestionably all these signals 2D NMR techniques: HETCOR and gHMBC
were used. Whereas the HETCOR spectrum permitted the assignment of the tertiary carbon signals and
the proton signals via one-bond correlations, the gHMBC spectrum made possible the assignment of the
quaternary carbon signals via two-bond and three-bond correlations with the proton signals. These corre-
lations allowed the unambigous determinations of the proton and carbon signals in dithiins (2) and (3)
(Table 2).
Table 2. The complete 1H and 13C NMR spectral assignment and summary of the HETCOR and gHMBC
correlations for both dithiins (2) and (3)
Dithiin
1H NMR
spectral assignment
δ (ppm)
13C NMR
spectral assignment
δ (ppm)
HETCOR
One-bond
coupling
δ (ppm)
g HMBC
two-bond
three- bond
coupling
δ (ppm)
coupling
δ (ppm)
(2)
H1/H6 (8.58, s)
C1/C6 (148.03)
C3/C8 (148.50)
C4/C9 (123.27)
C4a/C9a (145.00)
C5a/C10a (129.54)
C1/C9 (148.48)
C3/C7 (148.42)
C4/C6 (123.29)
C4a/C5a (144.21)
C9a/C10a (130.09)
8.58/148.03 8.58/129.54 8.58/145.00
8.45/148.50 8.45/123.27 8.58/148.50
7.39/123.27 7.39/148.50 8.45/145.00
8.45/148.03
H3/H8 (8.45, d, J=5.0 Hz)
H4/H9 (7.39, d, J=5.0 Hz)
7.39/129.54
(3)
H1/H9 (8.63, s)
8.63/148.48 8.63/130.09 8.63/144.21
8.46/148.42 8.46/123.29 8.63/148.42
7.38/123.29 7.38/148.42 8.46/144.21
8.46/148.48
H3/H7 (8.46, d, J=5.0 Hz)
H4/H6 (7.38, d, J=5.0 Hz)
7.38/130.09
Comparison of dipyrido-1,4-dithiins (2) and (3).
Tricyclic dipyrido-1,4-dithiins (2) and (3) represent two classes of symmetry: point groups C2h and C2v .
We found in our previous paper8 pentacyclic diquino-1,4-dithiins (15-18) of the C2h and C2v symmetry to
show some regularities in physical (mp, Rf) and spectroscopic data (1H NMR and MS) which enabled
their distinction. In this paper we would like to show some regularities in physical and spectroscopic data
connected with the symmetry of dipyrido-1,4-dithiins (2) and (3). Similar to our previous findings dithiin

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HETEROCYCLES, Vol. 65, No. 11, 2005
Cq2 (144.2)24
S
Cq1 (129.54)
Cq1 (155.16)23
C2h symmetry
S
S
N
N
N
N
N
S
2
S
N
N
S
Cq1 (126.7)24
Cq2 (145.00)
Cq2 (129.82)23
15
21
Cq2 (141.6)24
S
Cq1 (156.95)23
N
Cq1 (130.09)
N
C2v symmetry
S
S
N
N
N
S
3
S
S
Cq2 (127.98)23
16 Cq1 (128.9)24
Cq2 (144.21)
22
Scheme 7
with the C2h symmetry (2) showed higher melting point and higher Rf values (a more mobile isomer) than
the isomer with the C2v symmetry (3) as a result of its higher thermal stability and less polarity (Table 3).
Table 3. Comparison of the physical and spectroscopic data of dipyrido-1,4-dithiins (2) and (3)
No Physical and spectroscopic data
Dipyrido-1,4-dithiins
(2)
(3)
1
2
Melting point (oC)
TLC (Rf, spot colour)
a. silica gel, CHCl3-C2H5OH (10:1)
b. aluminum oxide, CH2Cl2
13C NMR, δ (ppm)
Cq1
174-17512
146-147
0.54 pale pink
0.55 pale pink
0.50 pale pink
0.48 pale pink
3
129.54
145.00
130.09
144.21
Cq2
4
MS 70 eV, m/z (%)
a. 218 (M)
100
48
6
100
37
5
b. 191 (M-HCN)
c. 186 (M-S)
d. 174 (M-CS)
12
11
13
Analyzing quaternary carbon signals of the dithiin ring in the C NMR spectra of dipyrido-1,4-dithiins
(2) and (3), isomeric dipyrido-1,4-dithiins (21) and (22)23 and the quinoline analogs (15) and (16),24 we
found regularity connected with an influence of the both electron-accepting nitrogen atoms on the chemi-
cal shift (Scheme 7). In all these pairs of isomers the carbon Cq1 signal is found more upfield and the
carbon Cq2 signal more downfield for the isomers with C2h symmetry in comparison to the isomers with
C2v symmetry. These data enable distinction both isomers.

HETEROCYCLES, Vol. 65, No. 11, 2005
2627
MS spectra of dipyrido-1,4-dithiins (2) and (3) showed formation of [M-S]+., [M-HCN]+. and [M-CS]+.
fragmentary ions but in contrast to diquino-1,4-dithiins (15-18) we could not find any differences
between the isomers.
EXPERIMENTAL
Melting points were determined in open capillary tubes on a Boetius melting point apparatus and are un-
corrected. The 1H and 13C NMR spectra and the HETCOR correlations were recorded on a Varian Unity-
Inova-300 spectrometer at 300.08 and 75.45 MHz in deuteriochloroform and dimethyl sulphoxide-d6 with
tetramethylsilane as the internal standard. The gHMBC correlations were recorded on a Bruker DRX
spectrometer at 500.13 and 125.77 MHz. Electron impact mass spectra (EI MS) were run on a Finnigan
MAT 95 spectrometer at 70 eV. The thin layer chromatography of dipyrido-1,4-dithiins (2) and (3) were
performed on silica gel 60 F254 (Merck 1.05735) with chloroform-ethanol (10:1 v/v) and on aluminum
oxide 60 F254 neutral (type E) (Merck 1.05581) with methylene chloride as eluent.
Synthesis
4-Chloro-3-nitropyridine (1) and 3-amino-4-chloropyridine (11)
4(1H)-Pyridinone was nitrated with fuming nitric acid and 30% oleum to give 3-nitro-4(1H)-pyridinone
according to described procedure25 [mp 279-280 oC (water), lit.,25 mp 280-281 oC]. As the published25 1
H
NMR spectrum showed the acidic NH proton at a dubious region of δ = 3.60 ppm, we re-examined the
1
spectrum: H NMR (DMSO-d6) δ: 6.48 (d, J = 7.5 Hz, 1H, H5), 7.77 (dd, J = 1.2 and 7.5 Hz, 1H, H6),
8.79 (d, J = 1.2 Hz, 1H, H2), 12.3 (br s, 1H, NH). When nitration was performed with more concentrated
acids the main product was 3,5-dinitro-4(1H)-pyridinone [mp > 300 oC (water), lit.,26 mp 325 oC].
3-Nitro-4(1H)-pyridinone was chlorinated with phosphorus pentachloride and phosphorus oxychloride to
o
o
1
give 4-chloro-3-nitropyridine (1) according to described procedure27 (mp 43-45 C, lit.,27 mp 45 C). H
NMR (CDCl3) δ: 7.56 (d, J = 5.4 Hz, 1H, H5), 8.71 (d, J = 5.4 Hz, 1H, H6), 9.14 (s, 1H, H2).
3-Amino-4-chloropyridine (11) was obtained by reduction of 4-chloro-3-nitropyridine (1) with tin
chloride according to described procedure28 [mp 58-59 oC (petroleum ether), lit.,29 mp 59.5-60.5 oC].
Reactions of 4-chloro-3-nitropyridine (1) with sulfur reagents
A. With sodium hydrogensulfide
To a solution of 4-chloro-3-nitropyridine (1) (0.32 g, 2 mmol) in ethanol (5 mL) sodium hydrogensulfide
(NaSH x nH2O, Aldrich, 0.5 g, ca. 5 mmol) was added and the reaction mixture was boiled for 10 min.
After cooling ethanol was evaporated in vaccuo, water (2 mL) was added to the residue. An insoluble
solid was filtered off, washed with water and air-dried to give 3,3’-dinitro-4,4’-dipyridinyl disulfide (7)
o
o
(0.06 g, 19%); mp 234-235 C (ethanol), lit.,27 mp 235 C. 1H NMR (CDCl3) δ: 7.74 (d, J = 5.5 Hz, 1H,
H5), 8.70 (d, J = 5.5 Hz, 1H, H6), 9.49 (s, 1H, H2). The filtrate was acidified with 10% hydrochloric acid

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HETEROCYCLES, Vol. 65, No. 11, 2005
to pH = 5. The resulting yellow solid was filtered off, washed with water and air-dried to give
o
o
1
4-mercapto-3-nitropyridine (6) (0.20 g, 64%); mp 152-154 C, lit.,27 mp 153 C). H NMR (DMSO-d6)
δ: 7.90 (d, J = 5.4 Hz, 1H, H5), 8.70 (d, J = 5.4 Hz, 1H, H6), 9.43 (s, 1H, H2), 13.2 (br s, 1H, SH).30
When this reaction was carried out for 30 min. 3,3’-dinitro-4,4’-dipyridinyl disulfide (7) (0.22 g, 71%)
and 4-mercapto-3-nitropyridine (6) (0.02 g, 6%) was isolated.
B. With thiourea
A solution of 4-chloro-3-nitropyridine (1) (0.159 g, 1 mmol) and thiourea (0.152 g, 2 mmol) in methanol
(4 mL) was boiled for 2 h. After cooling the resulting solid was filtered off, washed with water and air-
dried to give 3,3’-dinitro-4,4’-dipyridinyl disulfide (7) (0.11 g, 71%); mp 234-235 oC (ethanol), lit.,27 mp
o
235 C. The filtrate was diluted with water (8 mL), alkalized with 10% aqueous sodium hydroxide and
next acidified with 15% hydrochloric acid to pH = 5. The resulting yellow solid was filtered off, washed
o
with water and air-dried to give 4-mercapto-3-nitropyridine (6) (0.030 g, 19%); mp 152-154 C, lit.,27 mp
153 oC.
C. With sodium sulfide in ethanol
To a solution of 4-chloro-3-nitropyridine (1) (0.159 g, 1 mmol) in ethanol (5 mL) in an autoclave sodium
sulfide (0.234 g, 3 mmol) was added and the reaction mixture was let with argon and next heated at
o
150 C for 6 h. After cooling a resulting inorganic salt was removed by filtration, washed with ethanol
and the filtrate was evaporated to dryness. The residue was purified by column chromatography (silica gel,
o
chloroform) to give 4-ethoxy-3-nitropyridine (8) (0.140 g, 83%); mp 48-49 C (ether), lit.,31 mp 46.5-48
oC.
D. With sodium sulfide in HMPT
To a solution of 4-chloro-3-nitropyridine (1) (0.159 g, 1 mmol) in HMPT (3 mL) sodium sulfide (0.234 g,
o
3 mmol) was added and the reaction mixture was heated under argon on an oil bath at 155 C for 4 h.
After cooling the reaction mixture was poured into water (15 mL) and extracted with chloroform (3 x 10
mL). The extract was dried with anhydrous calcium chloride and evaporated in vaccuo. The residue was
purified by column chromatography (silica gel, chloroform) to give 4-dimethylamino-3-nitropyridine (9)
(0.160 g, 95%); mp 48-49 oC (ether), lit.,32 mp 48-49 oC.
3,3'-Dinitro-4,4'-dipyridinyl sulfide (10)
To a solution of 4-chloro-3-nitropyridine (1) (0.159 g, 1 mmol) in dry DMF (5 mL) 4-mercapto-3-nitro-
pyridine (6) (0.156 g, 1 mmol) was added, the mixture was let with argon and kept at 5 oC for 48 h. The
mixture was poured into water (15 mL) and the resulting solid was filtered off, washed with water and
o
air-dried to give 3,3’-dinitro-4,4’-dipyridinyl disulfide (7) (0.03 g, 19%); mp 234-235 C (ethanol),
o
lit.,27mp 235 C). The filtrate was extracted with chloroform (3 x 10 mL). The extract was dried with

HETEROCYCLES, Vol. 65, No. 11, 2005
2629
anhydrous calcium chloride and evaporated in vacuo. The residue was purified by column chroma-
tography (silica gel, chloroform) to give:
1. 3,3’-dinitro-4,4’-dipyridinyl sulfide (10) (0.11 g, 40%); mp 128-129 oC (ethanol), lit.,27 mp 129-130 oC.
1H NMR (CDCl3) δ: 7.26 (d, J = 4.8 Hz, 1H, H5), 8.72 (d, J = 4.8 Hz, 1H, H6), 9.39 (s, 1H, H2).
2. 3,3’-dinitro-4,4’-dipyridinyl disulfide (7) (0.02 g, 13%); mp 234-235 oC (ethanol), lit.,27 mp 235 oC.
Attempts of cyclization of 4-mercapto-3-nitropyridine (6)
A solution of 4-mercapto-3-nitropyridine (6) (0.156 g, 1 mmol) in MEDG (3 mL) or sulfolane (3 mL)
o
was heated under argon on an oil bath at 160 C for 2 h. After cooling the reaction mixture was poured
into water (9 mL) and the resulting solid was filtered off, washed with water and air-dried to give 3,3’-
dinitro-4,4’-dipyridinyl disulfide (7) (0.08 g, 52% in MEDG; 0.084 g, 54% in sulfolane); mp 234-235 oC
(ethanol), lit.,27 mp 235 oC.
Dipyrido-1,4-dithiins (2) and (3)
A. From sodium 3-nitro-4-pyridinethiolate (6A)
A solution of sodium 3-nitro-4-pyridinethiolate (6A) (0.18 g, 1 mmol) (obtained from equimolar amounts
of 4-mercapto-3-nitropyridine and sodium methanolate in dry methanol followed by evaporation of the
solvent) in dry DMSO (3 mL) was heated under argon on an oil bath at 160 oC for 20 h. After cooling the
reaction mixture was poured into water (6 mL) and the resulting solid was filtered off, washed with water
and air-dried. The filtrate was extracted with chloroform (3 x 20 mL). The extract was dried with anhy-
drous sodium sulfate and evaporated in vacuo to dryness. Combined solids were separated by column
chromatography (silica gel, chloroform) to give:
1. dipyrido-1,4-dithiin (2) (0.031 g, 28%); mp 174-175 oC (ethanol), lit.,12 mp 174-175 oC.
2. dipyrido-1,4-dithiin (3) (0.023 g, 21%); mp 146-147 oC (ethanol). Anal. Calcd for C10H6N2S2: C 55.02,
H 2.77, N 12.83. Found: C 54.94, H 2.81, N 12.69.
B. From 3,3’-dinitro-4,4’-dipyridinyl disulfide (7)
To a solution of 3,3’-dinitro-4,4’-dipyridinyl disulfide (7) (0.31 g, 1 mmol) in dry DMSO (6 mL) sodium
hydroxide (0.12 g, 3 mmol) was added. The reaction mixture was heated under argon on an oil bath at
o
160 C for 20 h. After cooling the reaction mixture was poured into water (6 mL) and extracted with
chloroform (3 x 20 mL). The extract was dried with anhydrous calcium chloride and evaporated in vacuo
to dryness. Combined solids were separated by column chromatography (silica gel, chloroform) to give
dipyrido-1,4-dithiin (2) (0.06 g, 28%) and dipyrido-1,4-dithiin (3) (0.06 g, 28%).
C. From 3-amino-4-chloropyridine (11)
To a solution of 3-amino-4-chloropyridine (11) (1.00 g, 7.8 mmol) in 20% solution of sulfuric acid (8
mL) at -10oC aqueous solution (2 mL) of sodium nitrite (0.60 g, 8.7 mmol) was added dropwise keeping
the temperature. Next aqueous solution (3 mL) of potassium xanthate (2.50 g, 15.6 mmol) was added

2630
HETEROCYCLES, Vol. 65, No. 11, 2005
dropwise and the resulting solid was filtered off using chilled funnel. The filtrate was extracted with
carbon tetrachloride (3 x 20 mL). Combined extracts (the solid was also dissolved in carbon tetrachloride)
were dried with anhydrous calcium chloride and evaporated to half volume under vacuo, boiled for 10
min and next evaporated to the dryness to obtain an oil (1.3 g). The oil was dissolved in DMF (10 mL)
and potassium hydroxide (0.5 g, 8.9 mmol) was added and the reaction mixture was boiled for 2.5 h.
After cooling the solvent was evaporated and the residue was dissolved in chloroform (15 mL). The
solution was washed with water, dried with calcium chloride and evaporated to the dryness. Separation by
column chromatography (silica gel, chloroform) gave:
1. dipyrido-1,4-dithiin (2) (0.30 g, 36%),
2. dipyrido-1,4-dithiin (3) (0.03 g, 4%),
3. pyridodithiolethione (13) (0.06 g, 4%); mp 157-158 oC (ethanol), lit.,12 mp 158 oC.
1
4. 3,4-diethylthiopyridine (14) (0.11 g, 7%); an oil. H NMR (CDCl3) δ: 1.29 (t, J = 7.4 Hz, 3H, CH3),
1.43 (t, J = 7.5 Hz, 3H, CH3), 2.94 (q, J = 7.5 Hz, 2H, CH2), 2.99 (q, J = 7.4 Hz, 2H, CH2), 7.03 (d, J = 5.3
Hz, 1H, H5), 8.32 (d, J = 5.3 Hz, 1H, H6), 8.44 (s, 1H, H2). EI MS (70 eV) 199 (M, 100), 177 (M-C2H4,
62). Anal. Calcd for C9H13NS2: C 54.23, H 6.57, N 7.03. Found: C 54.09, H 6.62, N 6.97.
D. from pyridinedithiolethione (13)
To a solution of pyridodithiolethione (13) (0.185 g, 1 mmol) in dry DMF (5 mL) potassium hydroxide
(0.11 g, 2 mmol) was added and the mixture was boiled for 3 h. After cooling the solvent was evaporated
in vacuo and the residue was dissolved in chloroform (5 mL) and washed with water. The extract was
dried with calcium chloride and evaporated in vacuo to give pure dipyrido-1,4-dithiin (2) (0.10 g, 92%).
Isomerization of dipyrido-1,4-dithiin (2) to dipyrido-1,4-dithiin (3)
o
To a suspension of dipyrido-1,4-dithiin (2) (0.218 g, 1 mmol) in dry DMSO (5 mL) at 70 C sodium
o
methanethiolate (0.084 g, 1.2 mmol) was added. The mixture was stirred at 170 C for 30 min. After
cooling the reaction mixture was poured into 15% aqueous sodium hydroxide (15 mL), diluted with water
(40 mL) and boiled for 1 h. The resulting solid was filtered off, washed with water, air-dried and
separated by preparative thin layer chromatography (aluminum oxide, methylene chloride) to give:
(1) dipyrido-1,4-dithiin (3) (0.110 g, 50%).
(2) dipyrido-1,4-dithiin (2) (0.070 g, 32%).
Attempts of isomerization of dipyrido-1,4-dithiin (3) to dipyrido-1,4-dithiin (2)
o
To a suspension of dipyrido-1,4-dithiin (3) (0.218 g, 1 mmol) in dry DMSO (5 mL) at 70 C sodium
o
methanethiolate (0.084 g, 1.2 mmol) was added. The mixture was stirred at 170 C for 30 min. After
cooling the reaction mixture was poured into 15% aqueous sodium hydroxide (15 mL), diluted with water
(40 mL) and boiled for 1 h. The resulting solid was filtered off, washed with water, air-dried to give
dipyrido-1,4- dithiin (3) (0.190 g, 87%).

HETEROCYCLES, Vol. 65, No. 11, 2005
2631
3’,4-Dimethylthio-3,4’-dipyridinyl sulfide (19)
o
To a suspension of dipyrido-1,4-dithiin (2) (0.218 g, 1 mmol) in dry DMSO (5 mL) at 70 C sodium
methanethiolate (0.084 g, 1.2 mmol) was added. The mixture was stirred for 30 min. After cooling the
reaction mixture was poured into 15% aqueous sodium hydroxide (15 mL) and methyl iodide (0.1 mL,
1.6 mmol) was added. The resulting solid was filtered off, washed with water, air-dried and purified by
column chromatography (silica gel, chloroform) to give 3’,4-dimethylthio-3,4’-dipyridinyl sulfide (19)
(0.220 g, 79%); mp 115-116 oC (ethanol). 1H NMR (CDCl3) δ: 2.60 (s, 3H, CH3), 6.41 and 7.03 (2d, J =
5.3 and 5.4 Hz, 2H, H5 and H5’), 8.15 and 8.58 (2d, J = 5.3 and 6.4 Hz, 2H, H6 and H6’), 8.47 and 8.59
(2s, 2H, H2 and H2’). EI MS (70 eV) 280 (M, 100), 233 (M-SCH3, 81.2), 218 (M-CH3SCH3, 82.3). Anal.
Calcd for C12H12N2S2: C 51.40, H 4.31, N 9.99. Found: C 51.22, H 4.32, N 9.84.
4,4’-Dimethylthio-3,3’-dipyridinyl sulfide (20)
o
A. To a suspension of dipyrido-1,4-dithiin (3) (0.218 g, 1 mmol) in dry DMSO (5 mL) at 70 C sodium
methanethiolate (0.084 g, 1.2 mmol) was added. The mixture was stirred for 30 min. After cooling the
reaction mixture was poured into 15% aqueous sodium hydroxide (15 mL) and methyl iodide (0.1 mL,
1.6 mmol) was added. The resulting solid was filtered off, washed with water, air-dried and purified by
column chromatography (silica gel, chloroform) to give 4,4’-dimethylthio-3,3’-dipyridinyl sulfide (20)
(0.22 g, 79%); 122-123 oC (ethanol). 1H NMR (CDCl3) δ: 2.48 (s, 3H, CH3), 7.05 (d, J = 5.3 Hz, 1H, H5),
8.38 (d, J = 5.3 Hz, 1H, H6), 8.31 (s, 1H, H2). EI MS (70 eV) 280 (M, 70), 233 (M-SCH3, 74), 218 (M-
CH3SCH3, 100). Anal. Calcd for C12H12N2S2: C 51.40, H 4.31, N 9.99. Found: C 51.32, H 4.36, N 9.89.
o
B. To a suspension of dipyrido-1,4-dithiin (2) (0.218 g, 1 mmol) in dry DMSO (5 mL) at 70 C sodium
o
methanethiolate (0.084 g, 1.2 mmol) was added. The mixture was stirred at 170 C for 30 min. After
cooling the reaction mixture was poured into 15% aqueous sodium hydroxide (15 mL) and methyl iodide
(0.1 mL, 1.6 mmol) was added. The resulting solid was filtered off, washed with water, air-dried and
separated by column chromatography (silica gel, chloroform) to give:
1. 3’,4-dimethylthio-3,4’-dipyridinyl sulfide (19) (0.105 g, 38%); mp 115-116 oC (ethanol).
2. 4,4’-dimethylthio-3,3’-dipyridinyl sulfide (20) (0.115 g, 41%); mp 122-123 oC (ethanol).
X-Ray analysis
A. Dipyrido-1,4-dithiin (2):
Data were measured on a Nonius KappaCCD diffractometer with graphite monochromated MoKα
radiation (λ = 0.70930 Å). The structure was solved by direct methods (SHELXS-97)33 and refined by
full-matrix least-squares minimization based on all unique F2 (SHELXL-97).34
Crystal data: C10H6N2S2, Mr = 218.29, monoclinic, a = 17.219(2), b = 3.9414(4), c = 14.031(2), β =
99.366(5), space group C2/c, Z = 4, V = 939.6(2) Å3, µ = 0.520 mm-1. 6106 reflections were collected of

2632
HETEROCYCLES, Vol. 65, No. 11, 2005
which 664 were unique and 577 with I > 2σ(I) (Rint = 0.016). The structure was refined to R = 0.039 and
Rw = 0.121.
B. Dipyrido-1,4-dithiin (3):
The crystall was twinned and the twin law [1 0 1; 0 –1 0; 0 0 –1]was applied during the refinement with a
final fraction of 0.37(2) for the second component. Data were collected at the Swiss Norwegian Beamline
at the European Synchrotron Radiation facility (λ = 0.9250 Å) in Grenoble (France). Data were integrated
with the software CrysalisCCD (Oxford Diffraction, 2004). The structure was solved by direct method
using the SIR9235 programs within the WINGX software suite36.The structure was refined by full-matrix
least-squares minimization on F2 in the program Crystals.37
Crystal data: C10H6N2S2, Mr = 218.29, monoclinic, a = 18.9992(7), b = 3.9440(2), c = 13.522(1), β =
110.902(6), space group Pc, Z = 2, V = 946.6(1) Å3, µ = 0.516 mm-1. 36147 reflections were collected of
which 5131 were unique (Rint = 0.071) and 2925 with I > 2σ(Ι). The structure was refined to R = 0.049
and Rw = 0.121.
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1
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