Synthesis of 4-substituted 6-dinitrobenzo[d]isothiazoles from 2,4,6-trinitrotoluene

Article abstract of DOI:10.1070/MC2005v015n05ABEH002128

The synthesis of 4,6-dinitrobenzo[d]isothiazole from a product obtained by the replacement of the ortho-NO₂ group in N-2,4,6- trinitrobenzylidene-4′-N,N-dimethylaminoaniline on treatment with PhCH₂SH was developed.

Full text of DOI:10.1070/MC2005v015n05ABEH002128

, 2005, 15(5), 200–202
Synthesis of 4-substituted 6-dinitrobenzo[d]isothiazoles from 2,4,6-trinitrotoluene
Oleg Yu. Sapozhnikov, Elena V. Smirnova, Mikhail D. Dutov, Vadim V. Kachala and Svyatoslav A. Shevelev*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328; e-mail: Shevelev@.ioc.ac.ru
DOI: 10.1070/MC2005v015n05ABEH002128
The synthesis of 4,6-dinitrobenzo[d]isothiazole from a product obtained by the replacement of the ortho-NO2 group in N-2,4,6-tri-
nitrobenzylidene-4'-N,N-dimethylaminoaniline on treatment with PhCH2SH was developed.
The aim of this study on the chemistry of 2,4,6-trinitrotoluene
(TNT) was to use TNT as a versatile and accessible raw chemi-
cal.1,2 Previously, we synthesised the derivatives of 4,6-dinitro-
benzo[b]thiophene3 and 4,6-dinitrobenzo[d]isothiazolium salts4
from TNT. The synthesis involves the preliminary conversion
of the TNT methyl group into groups with C=C or C=N double
bonds, the selective replacement of the ortho-NO2 group by
treatment with PhCH2SH in the presence of bases to give
ortho-PhCH2S derivatives, and the treatment with SO2Cl2. The
resulting derivatives ortho-SCl add in situ to a double bond
(C=C or C=N) to give the above compounds.
We studied the reaction of TNBA with benzylmercaptane
in N-methylpyrrolidone (N-MP) in the presence of K2CO3
(Scheme 2). In addition to replacement products 3a and 3b
1
(according to H NMR data, the 3a/3b ratio is 5:2),† we also
observed the products of replacement of two nitro groups,
which complicate the separation considerably. Crystallization
from an ethanol–acetonitrile mixture (1:1) allowed us to isolate
sulfide 3a in 12% yield.
Sulfide 3a can be synthesised by preliminary substitution of
the nitro group in compound 1 on treatment with PhCH2SH.4
This results in compounds 4a and 4b in a 3:1 ratio. The hydro-
lysis of a mixture of these compounds resulted in compounds
3a and 3b in a ratio of 3:1 (Scheme 2); the final mixture did not
contain products of substitution of two nitro groups, and the
fraction of compound 3a was higher than that in the experiment
with TNBA. Crystallization from an ethanol–acetonitrile mixture
It is well known5,6 that TNT undergoes condensation at
the methyl group with 4-nitroso-N,N-dimethylaniline to give
N-2,4,6-trinitrobenzylidene-4'-N,N-dimethylaminoaniline 1;
the hydrolysis of this compound results in 2,4,6-trinitrobenz-
aldehyde (TNBA) 2 (Scheme 1).
200 Mendeleev Commun. 2005

, 2005, 15(5), 200–202
N
N
O
O
O
O2N
NO2
O2N
SCH2Ph O2N
NO2
i
N
N
O2N
NO2
O
NO2
NO2
3a
SCH2Ph
I2
2
3b
O2N
H2O
NO2
NO2
TNT
iii
HCl
N
N
N
N
NO2
O
1
O2N
NO2
N
N
ii
NO2
O2N
NO2
O2N
SCH2Ph O2N
NO2
2
Scheme 1
(1:1) gave sulfide 3a in 40% yield.
NO2
NO2
SCH2Ph
The reaction of 3a with SO2Cl2 in dichloroethane resulted in
the cleavage of the S-CH2Ph bond to give sulfenyl chloride 5
(Scheme 3), which was used in the reaction with a 20% solu-
tion of ammonia in methanol7 without additional purification.
4,6-Dinitrobenzo[d]isothiazole 6 was the only product of this
reaction (Scheme 3).‡
1
4a
4b
Scheme 2 Reagents, conditions and results: i, 0.01 mol PhCH2SH +
0.01 mol K2CO3, 15 ml N-MP, 20 °C, 2 h [yield of 3a + 3b, 84% (5:2)];
ii, 0.01 mol PhCH2SH + 0.01 mol K2CO3, 15 ml N-MP, 20 °C, 3 h [yield
of 4a + 4b, 92% (3:1)]; iii, 2 g of 4a + 4b, 30 ml conc. HCl, 90 °C, 1 h
[yield of 3a + 3b, 87% (3:1)].
We studied the reactions of 4,6-dinitrobenzo[d]isothiazole 6
with various anionic nucleophiles. For example, the reaction
of compound 6 with thiophenol in N-MP in the presence of
K2CO3 at 20 °C gave a single product of the replacement of a
nitro group. According to NMR data (NOE), this is a product of
replacement of the 4-NO2 group. The reaction of compound 6
with phenol also resulted in a replacement product of the 4-NO2
group (NMR data, NOE), but this reaction required a higher
temperature (90 °C). The same result was observed in the reac-
tion of compound 6 with sodium azide at 20 °C in DMF. Thus,
the regioselective replacement of the 4-NO2 group is typical
of the reactions of 4,6-dinitrobenzo[d]isothiazole 6 with anionic
nucleophiles.
†
1H NMR spectra were recorded on a Bruker AM-300 instrument.
O
O
Chemical shifts are reported relative to TMS. The melting points of the
resulting compounds were determined on a Boetius hot stage according
to Koffler (the heating rate was 4 K min–1).
O2N
SCH2Ph
O2N
SCl
i
ii
3a: mp 100–102 °C (MeCN–EtOH). 1H NMR (CDCl3) d: 10.22 (s,
1H, CHO), 8.61 (d, 1H, arom., 4J 2.0 Hz), 8.46 (d, 1H, arom., 4J 2.0 Hz),
7.31–7.26 (m, 5H, Ph), 4.29 (s, 2H, CH2). Found (%): C, 52.51; H, 2.98;
N, 8.63; S, 9.77. Calc. for C14H10N2O5S (%): C, 52.83; H, 3.17; N, 8.80;
S, 10.07.
NO2
NO2
3a
5
6: mp 119–121 °C (EtOH). 1H NMR ([2H6]DMSO) d: 9.77 (d, 1H,
arom., 4J 1.9 Hz), 9.72 (s, 1H, CH), 8.95 (d, 1H, arom., 4J 1.9 Hz). MS,
m/z: 225 [M+]. Found (%): C, 37.52; H, 1.25; N, 18.81; S, 14.01. Calc.
for C7H3N3O4S (%): C, 37.34; H, 1.34; N, 18.66; S, 14.24.
NO2
Nu
a Nu = SPh
b Nu = OPh
c Nu = N3
iii
N
S
N
1
7a: mp 92–94 °C (MeCN–EtOH). H NMR ([2H6]DMSO) d: 9.30 (s,
S
O2N
O2N
1H, CH), 9.16 (d, 1H, arom., 4J 1.9 Hz), 7.74 (d, 1H, arom., 4J 1.9 Hz),
7.61–7.48 (m, 5H, Ph). MS, m/z: 288 [M+]. Found (%): C, 53.86; H,
2.63; N, 9.49; S, 21.87. Calc. for C13H8N2O2S2 (%): C, 54.15; H, 2.80;
N, 9.72; S, 22.24.
6
7a–c
Scheme 3 Reagents, conditions and results: i, 2 equiv. SO2Cl2, ClCH2CH2Cl,
20 °C, 30 min; ii, 10 equiv. NH3 (30% in MeOH); THF, 20 °C, 10 min
(yield of 6, 54%); iii, (a) 0.01 mol PhSH + 0.01 mol K2CO3, 10 ml N-MP,
20 °C, 5 h (yield of 7a, 62%); (b) 0.01 mol PhOH + 0.01 mol K2CO3,
10 ml N-MP, 90 °C, 9 h (yield of 7b, 41%); (c) 0.01 mol NaN3, 10 ml
DMF, 20 °C, 24 h (yield of 7c, 58%).
7b: mp 87–89 °C (EtOH). 1H NMR ([2H6]DMSO) d: 9.32 (s, 1H, CH),
8.97 (d, 1H, arom., 4J 1.9 Hz), 7.62–7.51 (m, 2H, Ph), 7.41–7.26 (m,
4H, Ph + arom.). MS, m/z: 272 [M+]. Found (%): C, 57.42; H, 2.84; N,
10.44; S, 11.55. Calc. for C13H8N2O3S (%): C, 57.34; H, 2.96; N, 10.29;
S, 11.78.
7c: mp 156–159 °C (MeCN–EtOH). 1H NMR ([2H6]DMSO) d: 9.19
(s, 1H, CH), 9.04 (d, 1H, arom., 4J 1.9 Hz), 8.03 (d, 1H, arom., 4J 1.9 Hz).
Found (%): C, 37.74; H, 1.06; N, 31.38; S, 14.70. Calc. for C7H3N5O2S
(%): C, 38.01; H, 1.37; N, 31.66; S, 14.50.
One should pay attention to how readily the 4-NO2 group is
replaced in 4,6-dinitrobenzo[d]isothiazole 6 even in the absence
of electron-withdrawing groups in the isothiazole fragment. Pre-
viously, only 4,6-dinitrobenzo[d]isothiazoles with a substituent
at the 3-position, namely, 4,6-dinitrobenzo[d]isothiazol-3-one
and 3-chloro-4,6-dinitrobenzo[d]isothiazole were described.8,9
The first member of the series, i.e., nonsubstituted 4,6-dinitro-
benzo[d]isothiazole 6, as well as products of the nucleophilic
substitution of the 4-NO2 group in this compound, i.e., com-
pounds 7, have not been known before.
‡
PhCH2SH (0.01 mol) was added to a mixture of compound 1 (0.01 mol)
and K2CO3 (0.01 mol) in 15 ml of N-MP at 20 °C with stirring. After
stirring for 3 h at ~20 °C, the mixture was poured into water; the
precipitate formed was filtered off and dried. The resulting mixture of
compounds 4a and 4b was placed in 30 ml of concentrated HCl and
heated for 1 h at 90 °C. After cooling, the resulting precipitate was
filtered off and recrystallised from an EtOH–MeCN mixture (1:1). The
yield of compound 3a was 40%.
SO2Cl2 (0.02 mol) was added to sulfide 3a (0.01 mol) in 10 ml of
ClCH2CH2Cl. The solution was kept for 30 min at room temperature.
The solvent and an excess of SO2Cl2 were removed in vacuo. The
resulting oil was dissolved in 15 ml of THF; after that, a 30% NH3
solution in MeOH (2 ml) was added to the solution. After 10 min, the
mixture was poured into water; the resulting precipitate was filtered off
and purified by column chromatography (silica gel, CHCl3).
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Received: 20th January 2005; Com. 05/2451
202 Mendeleev Commun. 2005