A new approach to 4-alkylthio-1,3-dithiole-2-thione: An unusual reaction of a zinc complex of 1,3-dithole-2-thione-4,5-dithiolate

Article abstract of DOI:10.1021/ol015990n

(formula presented) A new and facille approach to 4-alkylthio-1,3-dithiole-2-thione starting from easily accessible reactants was described. This approach was based on the unusual reaction of a zinc complex of 1,3-dithiole-2-thione-4,5-dithiolate with electrophilic reagents in the presence of 3-picolyl chloride hydrochloride/or 4-picolyl chloride hydrochloride/or pyridine hydrochloride.

Full text of DOI:10.1021/ol015990n

ORGANIC
LETTERS
2001
Vol. 3, No. 12
1941-1944
A New Approach to
4-Alkylthio-1,3-dithiole-2-thione: An
Unusual Reaction of a Zinc Complex of
1,3-Dithole-2-thione-4,5-dithiolate
Chunyang Jia, Deqing Zhang,* Wei Xu, and Daoben Zhu*
Organic Solids Laboratory, Center for Molecular Sciences, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100080, China
dqzhang@infoc3.icas.ac.cn
Received April 16, 2001
ABSTRACT
A new and facile approach to 4-alkylthio-1,3-dithiole-2-thione starting from easily accessible reactants was described. This approach was
based on the unusual reaction of a zinc complex of 1,3-dithiole-2-thione-4,5-dithiolate with electrophilic reagents in the presence of 3-picolyl
chloride hydrochloride/or 4-picolyl chloride hydrochloride/or pyridine hydrochloride.
Since the discovery of the first organic metal TTF‚TCNQ
(TTF, tetrathiafulvalene; TCNQ, 7,7,8,8-tetracyanoquino-
dimethane),1 organic electron donors with a TTF backbone
have been widely investigated in terms of synthetic and
structural as well as physical aspects.2 The most conventional
route to these electron donors is based on the coupling of
1,3-thiole-2-thione (one) derivatives promoted by trialkyl
phosphite.3 Thus, the key precursors to these TTF-based
electron donors are 1,3-thiole-2-thione (one) derivatives.
Among them, 4,5-bisalkylthio-1,3-dithiole-2-thione 1 (Figure
1) can be routinely prepared by the reaction between a zinc
complex of 1,3-dithiole-2-thione-4,5-dithiolate 2 (Figure 1)
or the anion 1,3-dithiole-2-thione-4,5-dithiolate generated in
situ and suitable electrophilic reagents.4 The analogue of 1,
4-alkylthio-1,3-dithiole-2-thione 3 (Figure 1), however, is not
easily accessible. Only a few approaches to 3 were described,
which include the electrochemical method5 and that reported
(1) Ferraris, J.; Cowan, D. O.; Walatka, V. J.; Perlstein, J. H. J. Am.
Chem. Soc. 1973, 95, 948.
(2) See: Williams, J. M.; Ferraro, J. R.; Thorn, R. J.; Carlson, K. D.;
Geiser, U.; Wang, H. H.; Kini, A. M.; Whangbo, M.-H. Organic
Superconductors (including Fullerenes); Prentice Hall: Englewod Cliffs,
NJ, 1992.
(3) (a) Bechgaard, K.; Cowan, D. O.; Bloch, A. N. J. Org. Chem. 1975,
40, 746. (b) Engler, E. M.; Scott, B. A.; Etemad, S.; Penney, T.; Patel, V.
V. J. Am. Chem. Soc. 1977, 99, 5909. (c) Kini, A. M.; Parakka, J. P.; Geiser,
U.; Wang, H.-H.; Rivas, F.; DiNino, E.; Thomas, S.; Dudek, J. D.; Williams,
J. M. J. Mater. Chem. 1999, 9, 883. (d) Li, H.-X.; Zhang, D.-Q.; Zhang,
B.; Yao, Y.-X.; Xu, W.; Zhu, D.-B.; Wang, Z.-M. J. Mater. Chem. 2000,
10, 2063.
Figure 1.
10.1021/ol015990n CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/18/2001

by Otsubo et al. starting from trimethylsilylacetylene.6 In
this Letter, we wish to report a new approach to 4-alkylthio-
1,3-dithiole-2-thione 3.
With the initial goal of synthesizing 4,5-bis(3-picolylthio)-
1,3-dithiole-2-thione 1a (Figure 1), 3-picolyl chloride hydro-
chloride was reacted with the tetra(n-butyl)ammonium salt
of 2, TBA2‚[Zn(DMIT)2], at 50-60 °C (method A).7 After
neutralization with K2CO3 and purification, in contrast to
our expectation, a new compound in addition to 1a8 (isolated
in 4% yield) was obtained in 60% yield (Scheme 1). In its
and nine signals at 210.0, 128.8, 130.9, 136.7, 144.7, 149.9,
150.3, 123.7, and 39.7 ppm in its 13C NMR spectrum. On
the basis of these spectroscopic data, we proposed the
chemical structure of this new compound as 4-(3-picolylthio)-
1,3-dithiole-2-thione (3a).
To establish the structure of this unexpected compound
completely, single crystals of good quality were grown from
dichloromethane, and the X-ray diffraction analysis results9
confirmed that this compound was 3a. Figure 2 shows the
molecular structure of 3a.
Scheme 1
FAB-MS spectrum, a molecular ion peak at m/z 258 was
detected. Signals at 4.13 (s), 6.97 (s), and 7.64-8.78 (m)
1
ppm in a 2:1:4 ratio were found in its H NMR spectrum,
(4) Svenstrup, N.; Becher, J. Synthesis 1995, 215, and further references
therein.
(5) (a) Falsig, M.; Lund, H. Acta Chem. Scand. B 1980, 34, 591. (b)
Wawzonek, S.; Heilmann, S. M. J. Org. Chem. 1974, 39(4), 511.
(6) Morikami, T. A.; Otsubo, T. Synlett 1997, 319.
Figure 2. Molecular structure of compound 3a.
(7) The reaction was performed as follows: The mixture of TBA2‚
[Zn(DMIT)2] (2.15 g, 2.28 mmol) and 3-picolyl chloride hydrochloride (1.5
g, 9.15 mmol) dissolved in 50 mL of acetonitrile was stirred at 50-60 °C
for 2 h. After that, solvents were removed under reduced pressure. The
resulting solid was treated with 40 mL of a saturated solution of K2CO3.
The above suspension was extracted with CH2Cl2 (3 × 50 mL), and the
organic phase was combined, washed with water (3 × 20 mL), and dried
with anhydrous MgSO4. This dichloromethane solution was decolorized
by heating with activated charcoal. Column chromatography of the crude
product after removing the solvents on silica gel with ethyl acetate afforded
compound 3a as a yellow solid (0.70 g, 60%) and 1a as a yellow solid (6.7
mg, 4%).
By varying the reaction sequences, i.e., 3-picolyl chloride
hydrochloride was first neutralized by K2CO3 and reacted
further with TBA2‚[Zn(DMIT)2] (method B)10 at 50-60 °C,
only compound 1a was detected, as expected (Scheme 2).
(8) All new compounds as well as 3c and 3e were characterized by
spectroscopic methods and elemental analysis. 3a: mp 90-91 °C; 1H NMR
(CDCl3) δ 4.13 (s, 2H, -CH2-), 6.97(s, 1H, olefinc), 7.64-8.78 (m, 4H,
pyridine); 13C NMR (CDCl3) δ 210.0 (-CdS), 128.8, 130.9, 136.7, 144.7,
149.9, 150.3 (pyridine and olefinic), 123.7 (olefinic, CH) and 39.7 (-CH2-
); FAB-MS 258 (M + 1); IR ν (KBr) 1055 cm-1 (-CdS). Anal. Calcd for
C9H5NS4: C, 42.00; H, 2.74; N, 5.44. Found: C, 42.03; H, 2.55; N, 5.22.
3b: mp 111-112 °C; 1H NMR (CDCl3) δ 3.94(s, 2H, -CH2-), 6.897 (s,
Scheme 2
1H, olefinic), 7.18-7.21 (“dd”, 2H), 8.59-8.62 (“dd”, 2H) (pyridine); 13
C
Efforts were also made to prepare single crystals of 1a, and
its crystal structure was also determined.11 Figure 3 displays
the chemical structure of 1a.
NMR (CDCl3) δ 40.1 (-CH2-), 123.6 (CH, olefinic), 150.2, 145.1, 133.8,
133.5 (pyridine), 213.4 (-CdS); FAB-MS 258 (M + 1); IR ν (KBr) 1063
cm-1 (-CdS). Anal. Calcd for C9H5NS4: C, 42.00; H, 2.74; N, 5.44.
Found: C, 42.11; H, 2.57; N, 5.27. 3c: mp 71-72 °C (lit.6 mp 73.5-74.5
°C); 1H NMR (CDCl3) δ 2.51 (s, 3H, -CH3), 6.90 (s, 1H, olefinic); EI-MS
180 (M+, 100%); IR ν (KBr) 1061 cm-1 (-CdS). Anal. Calcd for
C4H4S4: C, 26.68; H, 2.24. Found: C, 26.45; H, 2.12. 3d: mp 80-81 °C;
1H NMR (CDCl3) δ 2.76-2.82 (t, J ) 6 Hz, -CH2-), 3.12-3.19 (t, J ) 6
Hz, -CH2-), 7.18 (s, 1H, olefinic); 13C NMR (CDCl3) 18.6 (-CH2-), 31.7
(-CH2-), 117.0 (-CN), 132.6, 135.0 (olefinic), 213.7 (-CdS); EI-MS 219
(M+, 100%); IR ν (KBr) 1062 cm-1 (-CdS). Anal. Calcd for C6H5NS4: C,
32.85; H, 2.30; N, 6.39. Found: C, 32.76; H, 2.21; N, 6.36. 3e: mp 44-45
(9) Crystal data for 3a: C9H7NS4, M ) 257.40, monoclinic, C2/c, a )
12.996(3), b ) 7.934(2), and c ) 22.205(4) Å, â ) 109.62(3)°, V ) 2156.6-
(8) Å3, Z ) 8, Dc ) 1.585 g‚cm-3. A total of 2152 observed reflections [I
> 2σ(I)] and 130 variable parameters converged to R ) 0.0357 and wR )
0.1062.
(10) A total of 42.15 mg (0.3mmol) of K2CO3 was dissolved in less
than 5 mL of water, and 100 mg (0.61 mmol) of 3-picolyl chloride
hydrochloride was added at room temperature. After the gas evolution was
stopped, a colorless dense liquid was present. Subsequently, 143.35 mg
(0.15 mmol) of TBA2‚[Zn(DMIT)2] dissolved in 15 mL of acetonitrile was
mixed with this dense liquid, and the solution was stirred at 50-60 °C for
1.5-2 h. The reaction mixture was filtered, and the solid residue was washed
twice with dichloromethane (20 mL). The combined filtrate and washings
were decolorized by activated charcoal. After removing the solvent, column
chromatography of the crude reaction mixture on silica gel with ethyl acetate/
methanol (10:1) afforded compound 1a as a yellow solid (85.5 mg, 75%).
(11) Crystal data for 1a: C30H24N4S10, M ) 380.57, monoclinic, P2-
(1)/c, a ) 19.646(4), b ) 5.849(1), and c ) 29.643(6) Å, â ) 101.67(3)°,
V ) 3335.8(11) Å3, Z ) 4, Dc ) 1.516 g‚cm-3. A total of 5037 observed
reflections [I > 2σ(I)] and 397 variable parameters converged to R ) 0.0384
and wR ) 0.1007.
1
°C (lit.5a mp 48 °C); H NMR (CDCl3) δ 3.99 (s, 2H, CH2), 6.77 (s, 1H,
olefinic), 7.21-7.40 (m, 5H, phenyl); EI-MS 256 (M+, 22%). IR ν (KBr)
1062 cm-1 (-CdS). Anal. Calcd for C10H8S4: C, 46.84; H, 3.14. Found: C,
46.42; H, 2.91. 1a: mp 107-109 °C; 1H NMR (CDCl3) δ 3.92 (s, 4H,
-CH2-), 7.15-7.31, 7.55-7.59, 8.49-8.58 (m, 8H, pyridine); 13C NMR
(CCl4) δ 57.0 (-CH2-), 123.8, 132.6, 136.6, 137.2, 148.9, 149.9 (pyridine,
olefinic), 213.3 (-CdS); FAB-MS 381 (M + 1); IR ν (KBr) 1058 cm-1
(-CdS). Anal. Calcd for C15H12N2S5: C, 47.34; H, 3.18; N, 7.36. Found:
C, 46.99; H, 3.14; N, 7.19. 1b: mp 144-145 °C; 1H NMR (CDCl3) δ 3.87
(s, 4H, -CH2-), 7.16-7.19 (d, J ) 6 Hz, 2H), 8.58-8.61 (d, J ) 6 Hz,
2H); 13C NMR (CDCl3) δ 38.6 (-CH2-), 123.6, 133.8, 136.3, 149.3, 150.0
(pyridine, olefinic), 213.372 (CdS); FAB-MS 381 (M + 1); IR ν (KBr)
1063 cm-1 (-CdS). Anal. Calcd for C15H12N2S5: C, 47.34; H, 3.18; N,
7.36. Found: C, 46.95; H, 3.08; N, 7.12.
1942
Org. Lett., Vol. 3, No. 12, 2001

Figure 3. The asymmetric unit of crystal 1a.
Similar reactions were conducted with 4-picolyl chloride
hydrochloride. Compounds 3b and 1b (Figure 1) were
obtained after purification in yields of 60% and 9%,
respectively, by method A. Only compound 1b was produced
(68%) with method B. Although method A and method B
differ only in the reaction sequences, completely different
reactions take place. Since both 3-picolyl chloride hydro-
chloride and 4-picolyl chloride hydrochloride are weakly
acidic, it seems that acidic reaction medium is essential for
the formation of 3a and 3b. Thus, we assume that compound
4 (Figure 4) is the key reaction intermediate for the above
reactions with method A. The unusual chemical reactivity
of 4 was once reported by Rauchfuss et al.12 A detailed
investigation of this reaction mechanism is in progress.
propionitrile, or benzyl chloride at 50-60 °C for 1-2 h.13
After separation and purification, the corresponding 4-alkyl-
thio-1,3-dithole-2-thiones 3c, 3d, and 3e (Figure 1) were
obtained in addition to the 4,5-bisalkylthio-1,3-dithole-2-
thiones 1c, 1d, and 1e (Figure 1) as indicated in Scheme 3.
Scheme 3
The reaction yield for 3c and 3e was not high, probably due
to the high reactivity of methyl iodide and benzyl chloride
which will induce them to react with TBA2‚[Zn(DMIT)2]
directly, forming 1c and 1e, respectively. Compound 3d, on
the contrary, was separated in fairly high yield. It should be
mentioned that the reaction condition was not optimized for
each case. Efforts are being made in this regard to improve
the reaction yield for 3c, 3d, and 3e. Among the compounds
3a-e, 3d is most interesting since 2-cyanoethyl is a good
protecting group widely employed in the chemistry of 1,3-
dithiole-2-thione-4,5-dithiolate,4 and it can be used for the
synthesis of other derivatives of 4-alkylthio-1,3-dithole-2-
thione.
Figure 4.
Accordingly, both 3-picolyl chloride hydrochloride and
4-picolyl chloride hydrochloride may be considered to have
two roles for the reactions in method A: weak acid and
electrophile. Therefore, by replacing 3-picolyl chloride
hydrochloride or 4-picolyl chloride hydrochloride with
pyridine hydrochloride and an appropriate electrophilic
reagent, it would be possible to prepare other analogues of
3a and 3b by an approach similar to method A. Preliminary
experimental results were rather encouraging. Namely,
pyridine hydrochloride and TBA2‚[Zn(DMIT)2] were reacted
with an electrophilic reagent such as methyl iodide, 3-bromo-
In summary, a new and facile approach to 4-alkylthio-
1,3-dithole-2-thione starting from easily accessible chemicals
was described. The reaction procedure including separation
and purification is rather straightforward. We are currently
(13) Typical procedure is as follows: To the solution of TBA2‚[Zn-
(DMIT)2] (568.3 mg, 0.6 mmol) in 15 mL of acetonitrile were added 0.2
mL (2.4 mmol) of 3-bromopropionitrile and 279.66 mg (2.4 mmol) of
pyridine hydrochloride. The mixture was heated to 50-60 °C and stirred
for 2 h at this temperature. The resulting mixture was filtered ho, and the
remaining solid was further washed with dichloromethane (3 × 20 mL)
for complete extraction of the product. The combined filtrate and washings
were decolorized by use of activated charcoal. After removing the solvent,
column chromatography of the crude reaction mixture on silica gel with
dichloromethane afforded compound 3d as a yellow solid (184 mg 70%)
and 1d (62 mg, 17%).
(12) (a) Galloway, C. P.; Doxsee, D. D.; Fenske, D.; Rauchfuss, T. B.;
Wilson, S. R.; Yang, X. Inorg. Chem. 1994, 33, 4537. (b) Chou, J.-H.;
Rauchfuss, T. B.; Szczepura, L. F. J. Am. Chem. Soc. 1998, 120, 1805.
Org. Lett., Vol. 3, No. 12, 2001
1943

doing mechanism studies for this novel method, in particular,
studying the effect of pyridine hydrochloride. We are also
investigating the possibility of replacement of pyridine
hydrochloride by other acids and whether only a catalytic
amount of suitable acid is needed for the formation 4-alkyl-
thio-1,3-dithole-2-thione. These results will be reported in
due course.
and the Major State Basic Research Development Program
(G2000077500). The authors thank Prof. Xianglin Jin of
Peking University for his kind help on crystal structural
analysis.
Supporting Information Available: CIF files of com-
pounds 1a and 3a. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. The present research work was fi-
nancially supported by the Chinese Academy of Sciences
OL015990N
1944
Org. Lett., Vol. 3, No. 12, 2001