Exchange reactions of 1,3-bis(nitroarylthio)propanes with propane-1,3-dithiols

Article abstract of DOI:10.1007/s11172-006-0232-0

Base-catalyzed reactions of propane-1,3-dithiols with 2-chloronitrobenzene, 3,4-dichloronitrobenzene, and 2-chloro-3-nitropyridine afforded 1,3-bis(nitroarylthio)propanes, whose thiolate-thiolate exchange with propane-1,3-dithiols gave dihydrobenzodithiep

Full text of DOI:10.1007/s11172-006-0232-0

Russian Chemical Bulletin, International Edition, Vol. 55, No. 1, pp. 168—171, January, 2006
168
Exchange reactions
of 1,3ꢀbis(nitroarylthio)propanes with propaneꢀ1,3ꢀdithiols
A. V. Miroshnichenko, D. V. Demchuk,ꢀ and G. I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328. Eꢀmail: demchuk@ioc.ac.ru
Baseꢀcatalyzed reactions of propaneꢀ1,3ꢀdithiols with 2ꢀchloronitrobenzene, 3,4ꢀdiꢀ
chloronitrobenzene, and 2ꢀchloroꢀ3ꢀnitropyridine afforded 1,3ꢀbis(nitroarylthio)propanes,
whose thiolate—thiolate exchange with propaneꢀ1,3ꢀdithiols gave dihydrobenzodithiepines.
Key words: 1ꢀchloroꢀ2ꢀnitrobenzene, propaneꢀ1,3ꢀdithiols, dihydrobenzodithiepines,
nucleophilic aromatic substitution, thiolate—thiolate exchange reaction.
Earlier,1 we have synthesized cyclic sulfides, namely,
At the first step, the Cl atom was replaced by the
dihydrobenzodithiepines (3), by substitution of the thiolate
anions from propaneꢀ1,3ꢀdithiols (2) for the Cl atoms in
1,2ꢀdichlorobenzene (1) (Scheme 1).
thiolate residue of dithiol 2 in the presence of NaHCO3 to
give thiol 5. The second step involved intramolecular subꢀ
stitution of the thiolate anion for the nitro group in thiol 5
under the action of KOH.
Based on those results and available data on the differꢀ
ent reactivities of the Cl atom and the nitro group in the
aromatic ring toward nucleophilic reagents2 (including
cyclization reactions3), here we synthesized 1,3ꢀbis(nitroꢀ
arylthio)propanes (6) and dihydrobenzodithiepines (3)
(Scheme 3).
Scheme 1
Scheme 3
With more reactive 1ꢀchloroꢀ2ꢀnitrobenzene (4a) inꢀ
stead of dichlorobenzene (1), the yield of the target prodꢀ
uct 3 decreased, probably because of polycondensation as
a side process. Nevertheless, the oneꢀpot reactions beꢀ
tween compounds 2 and 4a in the ratio 1 : 1 also yielded
dithiepines 3 in two steps (Scheme 2).
Scheme 2
We assumed that 1,3ꢀbis(arylthio)propanes 6 and reꢀ
lated compounds could serve as convenient units for deꢀ
sign of more complex cyclic structures such as crown
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 163—166, January, 2006.
1066ꢀ5285/06/5501ꢀ0168 © 2006 Springer Science+Business Media, Inc.

SNAr reactions of bis(nitroarylthio)propanes
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 1, January, 2006
169
Table 1. Synthesis of 1,3ꢀbis(nitroarylthio)propanes (6) and
dihydrobenzodithiepines (3)
otherwise, the formation of a mixture of two dithiepines
could be expected.
The reaction mechanism (see Scheme 4, pathway a)
includes generation of a thiolate anion from dithiol 2 in
alkaline medium, addition of the thiolate anion to the
aromatic ring at the C atom bound to the S atom, splitting
of the adduct anion into two thiolate anions 5, and cyꢀ
clization of the latter into dihydrobenzodithiepines 3.
In the case of 3,4ꢀdichloronitrobenzene 4b, the reacꢀ
tion of 2,2ꢀdiethylpropaneꢀ1,3ꢀdithiol (2c) with two
equivalents of compound 4b gave, through replacement
of the activated Cl atom in the latter, diarylation prodꢀ
uct 6d. At the second step, thiolate—thiolate exchange
between compound 6d and dithiol 2c followed by inꢀ
tramolecular replacement of the other Cl atom in the
aromatic residue yielded nitrobenzodithiepine 3d. Along
with benzene derivatives 4a and 4b, we used 2ꢀchloroꢀ3ꢀ
nitropyridine 4c for the synthesis of compounds 6 and 3
according to Schemes 3 and 4, which afforded products
6e and 3e with higher selectivity.
The chemical literature contains no systematic data
on nucleophilic replacement of alkylthio groups in
the aromatic ring by other alkylthio groups. However,
thiolate—thiolate exchange has been found in reactions
of aliphatic thiols with 2ꢀisopropylthioꢀ and 5ꢀtertꢀ
butylthioꢀ6ꢀnitroquinoline in the presence of K2CO34 and
in the reaction of sodium ethanethiolate with 1,4ꢀdiisoꢀ
propylthioꢀ2ꢀnitrobenzene, in which the isopropyl group
in position 1 is replaced by the ethylthio group.5 In these
compounds, as in compounds 6, the exchanged alkylthio
groups are activated by the oꢀnitro group.
Starting
reagent
R
R1
R2
X
Yields (%) of
the products
6
3
2a, 4a
2b, 4a
2c, 4a
2c, 4b
2c, 4c
H
Me
Et
Et
Et
NO2
NO2
NO2
Cl
H
H
H
CH
CH
CH
78 (a)
77 (b)
88 (c)
78 (d)
95 (e)
56 (a)
58 (b)
55 (c)
56 (d)
93 (e)
NO2 CH
H
NO2
N
sulfides. This could be possible in the case of plauꢀ
sible 1+1 intermolecular replacement of the nitro group
in compounds 6 by the thiolate anions of dithiols 2
(Scheme 4, pathway b). In addition, the formation of
both dithiepines 3 (as the result of nucleophilic transꢀ
thiylation) and oligomeric linear sulfides containing the
fragments of constituent structures 2 and 6 could not be
ruled out. To verify these assumptions, we synthesized
dinitro derivatives 6 and carried out their reactions with
dithiols 2 in the presence of KOH.
For the ratio 2 : 4 = 1 : 2.2, the yields of compounds 6
were 77—95%. According to the data obtained, the reacꢀ
tions of equivalent amounts of compounds 2 and 6 folꢀ
lowed the mechanism of thiolate—thiolate exchange folꢀ
lowed by intramolecular cyclization of nitro thiol 5. The
resulting compounds 3 containing a sevenꢀmembered ring
were isolated in 55—93% yields, the starting reagents beꢀ
ing completely consumed (see Table 1 and Scheme 4). In
the synthesis of diarylated adducts 6 and their subsequent
cyclization into dithiepines 3, the same dithiol 2 was used;
Thus, we demonstrated that the thiolate—thiolate exꢀ
change in reactions of bis(2ꢀnitrophenylthio)propanes
Scheme 4

170
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 1, January, 2006
Miroshnichenko et al.
13C NMR (50 MHz), δ: 7.5 (CH3); 27.8 (CH2); 39.0 (CH2S);
41.0 (C); 124.7, 125.6, 127.8, 133.3, 136.9 (C(1)); 146.8 (C(2)).
MS, m/z 406 [M]+.
with propaneꢀ1,3ꢀdithiols in the presence of KOH gives
rise to dihydrobenzodithiepines.
1,3ꢀBis(2ꢀchloroꢀ4ꢀnitrophenylthio)ꢀ2,2ꢀdiethylpropane (6d).
The yield was 78%, yellow crystals, m.p. 170.5—171.2 °C (toluꢀ
ene). Found (%): C, 48.37; H, 4.45; Cl, 14.45; N, 5.64; S, 13.06.
Experimental
NMR spectra were recorded on Bruker ACꢀ200, Bruker
WMꢀ250, and Bruker AMꢀ300 spectrometers in CDCl3. Chemiꢀ
cal shifts were measured relative to the signals for the solvent
(δ 7.25 and 77.0 for 1H and 13C, respectively). Melting points
were determined on a Kofler hot stage. TLC analysis was carried
out on Sorbfil UVꢀ254 plates. Silica gel 60 (0.063—0.200 mm,
Merck) was used for column chromatography. Mass spectra
were recorded on a KratosꢀMS30 instrument.
C19H20Cl2N2O4S2. Calculated (%): C, 48.00; H, 4.24; Cl, 14.91;
N, 5.89; S, 13.49. 1H NMR (300 MHz), δ: 0.93 (t, 6 H, Me, J =
7.4 Hz); 1.66 (q, 4 H, CH2, J = 7.4 Hz); 3.08 (s, 4 H, CH2S);
7.33 (d, 2 H, H(6), J = 8.8 Hz); 8.02 (dd, 2 H, H(5), J = 8.8 Hz,
J = 2.2 Hz); 8.12 (d, 2 H, H(3), J = 2.2 Hz). 13C NMR (50 MHz),
δ: 7.6 (CH3); 27.9 (CH2); 38.7 (CH2S); 41.1 (C); 121.9 (C(5)H);
124.2 (C(3)H); 126.1 (C(2)); 132.4 (C(6)H); 144.9 (C(1));
146.3 (C(4)).
The starting reagents propaneꢀ1,3ꢀdithiol (2a), 2,2ꢀdimethylꢀ
propaneꢀ1,3ꢀdithiol (2b), and 2,2ꢀdiethylpropaneꢀ1,3ꢀdithiol
(2c) were prepared as described earlier.6 Commercial comꢀ
pounds 1ꢀchloroꢀ2ꢀnitrobenzene (4a), 1,2ꢀdichloroꢀ4ꢀnitrobenꢀ
zene (4b), and 2ꢀchloroꢀ3ꢀnitropyridine (4c) were used without
additional purification.
2,2ꢀDiethylꢀ1,3ꢀbis(3ꢀnitroꢀ2ꢀpyridylthio)propane (6e). The
yield was 95%, yellow crystals, m.p. 76.0—77.0 °C. Found (%):
C, 49.67; H, 5.31; N, 13.49; S, 15.64. C17H20N4O4S2. Calcuꢀ
lated (%): C, 49.98; H, 4.93; N, 13.72; S, 15.70. 1H NMR
(250 MHz), δ: 0.91 (t, 6 H, Me, J = 7.6 Hz); 1.63 (q, 4 H,
CH2, J = 7.6 Hz); 3.47 (s, 4 H, CH2S); 7.13 (dd, 2 H, H(5),
J = 8.3 Hz, J = 4.6 Hz); 8.40 (dd, 2 H, H(4), J = 8.3 Hz,
J = 1.8 Hz); 8.63 (dd, 2 H, H(6), J = 4.6 Hz, J = 1.8 Hz).
13C NMR (75 MHz), δ: 7.9 (CH3); 28.3 (CH2); 36.1 (CH2S);
40.2 (C); 118.4 (C(5)H); 133.6 (C(3), C(4)); 152.7 (C(6)H);
158.0 (C(2)).
3,4ꢀDihydroꢀ2Hꢀ1,5ꢀbenzodithiepine (3a). Potassium hydrꢀ
oxide (100 mg, 1.5 mmol) and a solution of compound 6a (80 mg,
0.21 mmol) in anhydrous DMF (3 mL) were added under argon
to a stirred solution of 90% propaneꢀ1,3ꢀdithiol (2a) (40 mg,
0.21 mmol) in anhydrous DMF (8 mL). The reaction mixture
was stirred at room temperature for 2 h and poured into water
(150 mL) acidified with conc. HCl (2 mL, 22 mmol). The prodꢀ
uct was extracted with light petroleum (3×10 mL). The organic
layer was washed with water (2×20 mL), dried with MgSO4, and
concentrated. The residue was dried in vacuo and chromatoꢀ
graphed on SiO2 with light petroleum as the eluent (Rf 0.23).
The yield of compound 3a was 43 mg (56%), colorless crystals,
m.p. 62.5—63.9 °C (cf. Refs 8 and 9: m.p. 59.5—60.5 and
60—61 °C, respectively). 1H NMR (250 MHz), δ:9 2.30 (m, 2 H,
CH2); 2.86 (m, 4 H, CH2S); 7.15 (m, 2 H, H(7), H(8)); 7.62
(m, 2 H, H(6), H(9)). 13C NMR (62.90 MHz), δ:10 33.0 (CH2);
33.4 (CH2S); 127.8 (C(6)H, C(7)H, C(8)H, C(9)H); 134.0
(C(5a), C(9a)).
Compounds 3b, 3c, 3d, and 3e were obtained analogously
from compounds 2b and 6b, 2c and 6c, 2c and 6d, and 2c and 6e,
respectively.
3,3ꢀDimethylꢀ3,4ꢀdihydroꢀ2Hꢀ1,5ꢀbenzodithiepine (3b). The
yield was 58%, a colorless oil (Rf 0.35, light petroleum). 1H NMR
(300 MHz), δ:10 1.16 (s, 6 H, CH3); 2.79 (s, 4 H, CH2S); 7.08
(m, 2 H, H(7), H(8)); 7.45 (m, 2 H, H(6), H(9)).
3,3ꢀDiethylꢀ3,4ꢀdihydroꢀ2Hꢀ1,5ꢀbenzodithiepine (3c). The
yield was 55%, a colorless oil, Rf 0.33 (light petroleum) (cf.
Ref. 1: m.p. 43.5—44.5 °C). 1H NMR (250 MHz), δ: 0.85 (t,
6 H, Me, J = 7.3 Hz); 1.60 (q, 7.3, 4 H, CH2); 2.87 (s, 4 H,
CH2S); 7.05 (m, 2 H, H(7), H(8)); 7.40 (m, 2 H, H(6), H(9)).
13C NMR (62.9 MHz), δ: 7.6 (CH3); 26.2 (vbr, CH2); 41.1
(CH2S); 126.8 (br.s, C(6)H, C(7)H, C(8)H, C(9)H); 132.1 (br.s,
C(5a), C(9a)). MS, m/z 238 [M]+.
1,3ꢀBis(2ꢀnitrophenylthio)propane (6a). Potassium carbonꢀ
ate (414 mg, 3.0 mmol) and a solution of 1ꢀchloroꢀ2ꢀnitrobenꢀ
zene (4a) (347 mg, 2.2 mmol) in DMF (4 mL) were added under
argon to a stirred solution of 90% propaneꢀ1,3ꢀdithiol (2a)
(120 mg, 1.0 mmol) in anhydrous DMF (10 mL). The reaction
mixture was heated at 50 °C for 8 h, cooled, and poured
into water (150 mL) acidified with conc. HCl (2 mL, 22 mmol).
The product was extracted with ethyl acetate (3×10 mL). The
organic layer was washed with water (2×20 mL), dried with
MgSO4, and concentrated. The residue was dried in vacuo
and chromatographed on SiO2 with toluene as the eluent
(Rf 0.50). Recrystallization from toluene (3 mL) gave compound
6a (273 mg, 78%) as yellow crystals, m.p. 140.5—143.0 °C
(cf. Ref. 7: m.p. 140 °C). Found (%): C, 51.33; H, 3.87; N, 7.56;
S, 18.69. C15H14N2O4S2. Calculated (%): C, 51.41; H, 4.03;
1
N, 7.99; S, 18.30. H NMR (300 MHz), δ: 2.16 (m, 2 H, CH2,
J = 7.0 Hz); 3.16 (t, 4 H, CH2S, J = 7.0 Hz); 7.27 (td, 2 H,
H(4), J = 7.7 Hz, J = 1.5 Hz); 7.41 (dd, 2 H, H(6), J = 8.1 Hz,
J = 1.5 Hz); 7.53 (td, 2 H, H(5), J = 7.7 Hz, J = 1.5 Hz); 8.17
(dd, 2 H, H(3), J = 8.1 Hz, J = 1.5 Hz). 13C NMR (50 MHz), δ:
26.0 (CH2); 31.0 (CH2S); 124.8, 126.2, 126.7, 133.6, 136.7
(C(1)); 146.4 (C(2)).
Compounds 6b, 6c, 6d, and 6e were obtained analogously
from compounds 2b and 4a, 2c and 4a, 2c and 4b, and 2c and 4c,
respectively.
2,2ꢀDimethylꢀ1,3ꢀbis(2ꢀnitrophenylthio)propane (6b). The
yield was 77%, yellow crystals, m.p. 91.0—92.1 °C. Found (%):
C, 53.80; H, 4.66; N, 7.14; S, 17.31. C17H18N2O4S2. Calcuꢀ
lated (%): C, 53.95; H, 4.79; N, 7.40; S, 16.95. 1H NMR
(300 MHz), δ: 1.28 (s, 6 H, CH3); 3.09 (s, 4 H, CH2S); 7.21 (td,
2 H, H(4), J = 7.7 Hz, J = 1.5 Hz); 7.48 (m, 4 H, H(5), H(6));
8.05 (dd, 2 H, H(3), J = 8.1 Hz, J = 1.5 Hz). 13C NMR
(50 MHz), δ: 27.5 (CH3); 36.0 (C); 43.7 (CH2S); 124.7, 125.7,
127.7, 133.3, 136.9 (C(1)); 146.8 (C(2)).
2,2ꢀDiethylꢀ1,3ꢀbis(2ꢀnitrophenylthio)propane (6c). The yield
was 88%, yellow crystals, m.p. 84.6—86.5 °C. Found (%):
C, 56.05; H, 5.39; N, 6.72; S, 16.13. C19H22N2O4S2. Calcuꢀ
lated (%): C, 56.14; H, 5.45; N, 6.89; S, 15.78. 1H NMR
(300 MHz), δ: 0.90 (t, 6 H, Me, J = 7.5 Hz); 1.64 (q, 4 H, CH2,
J = 7.5 Hz); 3.04 (s, 4 H, CH2S); 7.19 (m, 2 H, H(4)); 7.48 (m,
4 H, H(5), H(6)); 8.03 (dd, 2 H, H(3), J = 8.0 Hz, J = 1.5 Hz).
3,3ꢀDiethylꢀ7ꢀnitroꢀ3,4ꢀdihydroꢀ2Hꢀ1,5ꢀbenzodithiepine
(3d). The yield was 56%, yellow crystals, m.p. 109.0—110.2 °C
(cf. Ref. 1: m.p. 82.0—83.4 °C). 1H NMR (300 MHz), δ: 0.84 (t,

SNAr reactions of bis(nitroarylthio)propanes
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 1, January, 2006
171
6 H, CH3, J = 7.4 Hz); 1.57 (q, 4 H, CH2, J = 7.4 Hz); 3.06 (s,
2 H, CH2S); 3.11 (s, 2 H, CH2S); 7.33 (d, 1 H, H(9), J = 8.4 Hz);
7.78 (dd, 1 H, H(8), J = 8.4 Hz, J = 2.3 Hz); 8.09 (d, 1 H, H(6),
J = 2.3 Hz). 13C NMR (62.9 MHz), δ: 7.8 (CH3); 26.2 (CH2);
39.9 (CH2S); 40.3 (CH2S); 120.6 (C(8)H); 126.1 (C(6)H);
131.1 (C(9)).
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3,3ꢀDiethylꢀ3,4ꢀdihydroꢀ2Hꢀ[1,4]dithiepino[2,3ꢀb]pyridine
(3e). The yield was 93%, yellowish crystals, m.p. 95.1—96.0 °C.
Found (%): C, 60.29; H, 7.41; N, 5.95; S, 26.55. C121H17NS2.
Calculated (%): C, 60.20; H, 7.16; N, 5.85; S, 26.79. H NMR
(250 MHz), d: 0.83 (t, 6 H, Me, J = 7.5 Hz); 1.55 (q, 4 H,
CH2, J = 7.5 Hz); 3.09 (s, 2 H, CH2S); 3.17 (s, 2 H, CH2S);
6.85 (dd, 1 H, C(7), J = 7.9 Hz, J = 4.6 Hz); 7.43 (dd, 1 H,
H(6), J = 7.9 Hz, J = 1.6 Hz); 8.15 (dd, 1 H, C(8), J = 4.6 Hz,
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(C(5a)H); 138.4 (C(6)H); 146.2 (C(8)H); 157.1 (C(9a)). MS,
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This work was financially supported by the Council on
Grants of the President of the Russian Federation (Proꢀ
gram for State Support of Leading Scientific Schools of
Russia, Grant NSh 02121ꢀ2003ꢀ3).
Received July 15, 2005;
in revised form November 28, 2005