Synthetic utilization of polynitroaromatic compounds. 2. Synthesis of 4,6-dinitro-1,2-benzisothiazol-3-ones and 4,6-dinitro-1,2-benzisothiazoles from 2-benzylthio-4,6-dinitrobenzamides

Article abstract of DOI:10.1021/jo000480c

Cyclization of 2-benzylthio-4,6-dinitrobenzamides to 4,6-dinitro-1,2-benzisothiazol-3-ones was achieved using SO₂Cl₂ in CH₂Cl² at room temperature. Alkylation of these heterocycles proceeded in a nonregioselective manner to yield a mixture of corresponding O- and N-alkylated products. Oxidation of 4,6-dinitro-1,2-benzisothiazoles (50% H₂O₂ in AcOH) afforded the corresponding S-oxides and S,S-dioxides, depending on oxidation conditions. Unexpectedly, oxidation of a 3-methoxy derivative resulted in ring opening with the formation of the corresponding sulfamide. Chlorination of these 4,6-dinitro-1,2-benzisothiazol-3-ones (PCl₅-POCl₃) gave the expected 3-chloroisothiazoles.

Full text of DOI:10.1021/jo000480c

J . Org. Chem. 2000, 65, 8439-8443
8439
Syn th etic Utiliza tion of P olyn itr oa r om a tic Com p ou n d s. 2.
Syn th esis of 4,6-Din itr o-1,2-ben zisoth ia zol-3-on es a n d
4,6-Din itr o-1,2-ben zisoth ia zoles fr om
2-Ben zylth io-4,6-d in itr oben za m id es
S. G. Zlotin,* P. G. Kislitsin, A. I. Podgursky, A. V. Samet, and V. V. Semenov
N.D. Zelinsky Institute of Organic Chemistry RAS, Leninsky Pr., 47 Moscow, 117913, Russia
A. C. Buchanan III and Andrei A. Gakh*
Chemical and Analytical Sciences Division, Oak Ridge National Laboratory,
Oak Ridge, Tennessee 37831-6197
gakhaa@ornl.gov
Received March 29, 2000
Cyclization of 2-benzylthio-4,6-dinitrobenzamides to 4,6-dinitro-1,2-benzisothiazol-3-ones was
achieved using SO2Cl2 in CH2Cl2 at room temperature. Alkylation of these heterocycles proceeded
in a nonregioselective manner to yield a mixture of corresponding O- and N-alkylated products.
Oxidation of 4,6-dinitro-1,2-benzisothiazoles (50% H2O2 in AcOH) afforded the corresponding
S-oxides and S,S-dioxides, depending on oxidation conditions. Unexpectedly, oxidation of a
3-methoxy derivative resulted in ring opening with the formation of the corresponding sulfamide.
Chlorination of these 4,6-dinitro-1,2-benzisothiazol-3-ones (PCl5-POCl3) gave the expected 3-chlor-
oisothiazoles.
In tr od u ction
bases,16-18 and reaction of nitro-substituted 2-chloroben-
zaldehydes with a mixture of sulfur and ammonia.9,10,19
In most cases, only 5- and 7-nitro-1,2-benzisothiazoles
and isothiazol-3-ones but not 4- and 6-nitro-isomers can
be prepared using these methods.
It is known that 1,2-benzisothiazoles and 1,2-benz-
isothiazol-3-ones, containing a nitro group in the aromatic
ring, possess bactericide,1-5 fungicide,6,7 and nematocide8
properties, and can be used as intermediates for azo
dyes.9,10 These compounds have been synthesized by
various methods including amination of 2-(chlorosulfa-
nyl)nitrobenzoyl chlorides3,11,12 chlorination of 2-(alkyl-
thio)nitrobenzamides7,13 and 2-(alkylthio)nitrobenzal-
doximes,4,14 reaction of 2-(alkylthio)nitrobenzaldoximes
with polyphosphoric acid,15 reaction of 2-(alkylsulfinyl)-
nitrobenzamides with trichloroacetic anhydride16,17 or
It is expected that 1,2-benzisothiazoles and 1,2-benz-
isothiazol-3-ones containing two nitro groups in the
aromatic ring would have useful biological activities as
well. They also may serve as valuable intermediates for
synthesis of other functionalized nitro- and dinitro-1,2-
benzisothiazoles or isothiazol-3-ones via alkylation, ha-
logenation, oxidation as well as reactions with nucleo-
philic reagents.
To the best of our knowledge, there is only one
literature report of a 1,2-benzisothiazole containing two
nitro groups in the aromatic ring. Thus, nitration of
4-chloro-1,2-benzisothiazole gave 4-chloro-5,7-dinitro-1,2-
benzisothiazole, patented as an intermediate for synthe-
sis of azo dyes.10 4,6-Dinitro-1,2-benzisothiazoles and 4,6-
dinitro-1,2-benzisothiazol-3-ones have not yet been
reported.
In our previous paper,20 we proposed to use 2,4,6-
trinitroaromatic compounds as possible starting materi-
als for synthesis of various aromatic and heterocyclic
intermediates. In the case of benzisothiazoles, a possible
synthetic strategy includes transformation of readily
available 2,4,6-trinitrotoluene (TNT) to 2,4,6-trinitrobenz-
amides, followed by substitution of an o-nitro group by
(1) Clarke, K.; Gleadhill, B.; Scrowston, R. M. J . Chem. Res. Synop.
1979, 12, 395.
(2) Vicini, P.; Mazza, P. Farmaco 1989, 44(5), 511.
(3) Fischer, R.; Hurni, H. Arz.-Forshung 1964, 14(12), 1301.
(4) Kagano, H.; Goda, H.; Yoshida, K.; Yamamoto, M.; Sakaue, S.
Can. Pat. Appl. CA 2,151,074 (Cl. C07D275/04), 1996; Chem. Abstr.
1996, 124, 317152h.
(5) Zani, F.; Mingiardi, M. R.; Maggiali, C. A.; Mazza, P. Farmaco
1996, 51(11), 707.
(6) Hagen, H.; Ziegler, H.; Pommer, E. H.; Ammermann, E. Ger.
Offen. DE 3,202,298 (C1. C07D275/04), 1983; Chem. Abstr. 1983, 99,
175752t.
(7) Kagano, H.; Itsuda, H.; Sakagami, S. J . P. 07,330,745 [95,330,-
745] (C1. C07D275/04), 1995; Chem. Abstr. 1996, 124, 289523j.
(8) Sutter, M.; Kunz, W. Eur. Pat. Appl. EP 454,621 (Cl. C07D275/
04) 1991; Chem. Abstr. 1992, 116, 106280v.
(9) Hagen, H.; Markert, J . Ger. Offen. DE 3,018,108 (Cl. C07D275/
04), 1981; Chem. Abstr. 1982, 96, 68980g.
(10) Gruettner-Merten, S.; Grund, C.; Guldner, A.; Hagen, H.;
Reichelt, H.; Sens, R. Ger. Offen. DE 4,339,270 (C1. C09B29/09), 1995;
Chem. Abstr. 1995, 123, 259743t.
(11) Hagen, H.; Ziegler, H. Ger. Offen. DE 3,150,629 (Cl. C07D275/
04), 1983; Chem. Abstr. 1983, 99, 175750r.
(16) Wright, S. W.; Abelman, M. M.; Bostrom, L. L.; Corbett, R. L.
Tetrahedron Lett. 1992, 33(2), 153.
(17) Wright, S. W.; Petraitis, J .; Abelman, M. M.; Batt, D. G.;
Bostrom, L. L.; Corbett, R. L.; Decicco, C. P.; Di Meo, S. V.; Freimark,
B.; Giannaras, J . V.; Green, A. M.; J etter, J . M.; Nelson, D. J .; Orwat,
M. J .; Pinto, D. J .; Pratta, M. A.; Sherk, S. R.; Williams, J . M.; Magolda,
R. L.; Arner, E. S. J . Med. Chem. 1994, 37(19), 3071.
(18) Bamfield, P.; Greenwood, D.; Lotey, H.; Stirling, C. J . M. J .
Chem. Soc., Perkin Trans. 2 1988, (5), 691.
(19) Markert, J .; Hagen, H. Lieb. Ann. Chem. 1980, (5), 768.
(12) Ponci, R.; Gialdi, F.; Baruffini, A. Farmaco 1964, 19(3), 254.
(13) Kagano, H.; Goda, H.; Sakaue, S. Eur. Pat. Appl. EP 657,438
(Cl. C07D275/04), 1995; Chem. Abstr. 1995, 123, 313964b.
(14) Kagano, H.; Goda, H.; Yamamoto, M.; Sakaue, S.; Toudou, M.
PTC Int. Appl. WO 96 17,834 (C1. C07D275/04), 1996; Chem. Abstr.
1996, 125, 142716m.
(15) Rahman, L. K. A.; Scrowston, R. M. J . Chem. Soc., Perkin Trans.
1 1984, (3), 385.
10.1021/jo000480c CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/10/2000

8440 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
an alkylthio group, and cyclization to the desired 4,6-
dinitro-1,2-benzisothiazol-3-ones by chlorinating agents.
The retro-synthetic analysis is presented below.
We investigated the behavior of a series of N-substi-
tuted 2-benzylthio-4,6-dinitrobenzamides (5-10) to ex-
plore the scope of the cyclization reaction. Synthesis of
the starting benzamides (5-10) was described previ-
ously.20 We found that 5-10 reacted smoothly with SO2-
Cl2 in CH2Cl2 at room temperature to afford N-alkyl-
and N-aryl-4,6-dinitro-1,2-benzisothiazol-3-ones (11-16)-
in 55-91% yields (Scheme 2).
Sch em e 2
Conversion of TNT to 2,4,6-trinitrobenzoic acid and its
amides was described previously, as well as reaction of
these amides with alkyl- and arylmercaptans which
produced 2-(alkylthio)-4,6-dinitrobenzamides.20 In this
paper, we will describe cyclization of the 2-(alkylthio)-
4,6-dinitrobenzamides leading to the desired 4,6-dinitro-
l,2-benzisothiazol-3-ones, and some further reactions of
these compounds with electrophilic reagents.
2-Benzylthio-4-nitrobenzamides containing other elec-
tron withdrawing groups at the 6- position react simi-
larly. Thus, 2-benzylthio-6-benzylsulfonyl-4-nitrobenza-
mide (17)20 is easily converted to 4-benzylsulfonyl-6-nitro-
l,2-benzisothiazol-3-one (18) in 84% yield by treatment
with sulfuryl chloride at room temperature (Scheme 3).
It is noteworthy that the use of pure o-(benzylthio)-
benzamides in the cyclization reaction is not required.
Compounds 3, 5-10, and 17, containing the related
p-benzylthio isomers,20 could be used without further
purification. In these cases, isolation of analytically pure
nitro-1,2-benzisothiazol-3-ones (4, 11-16, and 18) is
achieved by simple recrystallization from i-PrOH or its
mixtures with heptane, CHCl3, or acetone.
Resu lts a n d Discu ssion
It is known that S-aryl-S-benzylsulfides easily react
with Cl2 or SO2Cl2 to give arylthiochloridesspossible
intermediates for synthesis of 1,2-benzisothiazoles.21
Examples include conversion of the N-phenylamide of
3-(benzylthio)pyridine-2-carboxylic acid to 2-phenylpyri-
doisothiazol-3-one by reaction with SO2Cl2.17 In addition,
synthesis of 1,2-benzisothiazole-3-ones by reactions of
2-(alkylthio)-N-arylbenzamides (alkyl ) C1-C4) with Cl2
or SO2Cl2 have been reported by J apanese authors in two
recent patents.7,13
To determine the effect of thioalkyl groups in 2-(alky-
lthio)-4,6-dinitrobenzamides on the yield of the desired
4,6-dinitro-l,2-benzisothiazol-3-ones, we have investi-
gated reactions of 2-(alkylthio)-4,6-dinitrobenzamides
(1-3)20 (Scheme 1) with sulfuryl chloride. It appeared
that 2-methoxycarbonylmethylthio-4,6-dinitrobenzamide
(1) did not react with SO2Cl2 in chlorohydrocarbons (CH2-
Cl2, CHCl3, CCl4) at 20-70 °C. On the other hand,
treatment of 2-methylthio- and 2-benzylthio-4,6-dini-
trobenzamides (2) and (3) with SO2Cl2 in CH2Cl2 at 15-
20 °C afforded the desired 4,6-dinitro-1,2-benzisothiazol-
3-one (4) in 64% and 98% yields, respectively (see also
ref 23). Based on these results, we selected 2-benzylthio-
4,6-dinitrobenzamides as starting compounds for syn-
thesis of 4,6-dinitro-1,2-benzisothiazol-3-ones.
Sch em e 3
It should be noted that benzyl chloride, a byproduct of
the cyclization process, can be easily isolated from the
reaction mixture by extraction with petroleum ether or
hexane. Hence, it can be reused for synthesis of the
starting 2-benzylthio-4,6-dinitrobenzamides. This feature
improves the potential for developing an industrial
process for production of the target heterocycles.
Sch em e 1
4,6-Dinitro-l,2-benzisothiazol-3-ones (4, 11-16) are
found to be useful intermediates in the synthesis of other
1,2-benzisothiazol-3-ones and 1,2-benzisothiazoles bear-
ing diverse substituents in isothiazole and benzene rings.
Thus, 4 reacts with dimethyl sulfate and benzyl chloride
in DMF in the presence of K2CO3 to afford mixtures of
3-alkoxy-4,6-dinitro-1,2-benzisothiazoles (19 and 20) and
2-alkyl-4,6-dinitro-1,2-benzisothiazol-3-ones (11 and 12)
in which products of O-alkylation 19 and 20 were the
principal components (Scheme 4). Products of O- and
N-alkylation were easily separated due to their different
solubility in hexane: 19 and 20 are much more soluble
(20) Zlotin, S. G.; Kislitsin, P. G.; Serebryakov, E. A.; Samet, A. V.;
Konyushkin, A. L.; Semenov, V. V.; Buchanan, A. C.; Gakh, A. A. J .
Org. Chem. 2000, 64, 8430. Previous communication: Zlotin, S. G.;
Serebryakov, E. A.; Kislitsin, P. G.; Konyushkin, L. D.; Semenov, V.
V.; Buchanan, A. C. III.; Gakh, A. A. Abstract Paper, The 218th ACS
National Meeting, New Orleans, 48-Orgn. Part 2, Aug 22, 1999.
(21) Hogg, D. R. In Sulfenic acids and their derivatives” in “Com-
prehensive Organic Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon
Press Ltd.: New York, 1979; Vol. 3.

Synthetic Utilization of Polynitroaromatic Compounds. 2
J . Org. Chem., Vol. 65, No. 25, 2000 8441
Sch em e 7
than 11 and 12. Reaction of 4 with ethylchloroacetate
under the same conditions afforded only (4,6-dinitro-1,2-
benzisothiazol-3-yl)oxyacetic acid ethyl ester (21) in 44%
yield.
Sch em e 4
1,2-Benzisothiazoles are generally much more resistant
toward oxidizers than 1,2-benzisothiazol-3-ones.22 We
found, however, that 4,6-dinitro-3-methoxy-1,2-benz-
isothiazole (19) reacted with 50% H2O2 in AcOH at 100
°C to afford 3,5-dinitro-2-(methoxycarbonyl)benzene-
sulfamide (28) in 84% yield. The reaction probably
involves formation of 4,6-dinitro-3-methoxy-1,2-benzisothi-
azole-S,S-dioxide (29) followed by a hydrolytic cleavage
of the CdN bond in 29 under the reaction conditions
(Scheme 8).
We also found that the carbonyl group in 4 can be
replaced with chlorine, probably via tautomer 4a . Indeed,
4 reacts with a mixture of PCl5 and POCl3 to give
3-chloro-4,6-dinitro-1,2-benzisothiazole (22) in 65% yield
(Scheme 5). Prolonged heating (20 h) of the reaction
mixture at 150 °C is required for completion of the
reaction.
Sch em e 8
Sch em e 5
Con clu sion s
As a result of our investigations (see also ref 20), new
synthetic routes for transformation of polynitroaromatic
compounds to 4,6-dinitro-1,2-benzisothiazoles and 4,6-
dinitro-1,2-benzisothiazol-3-ones have been developed.
The overall strategy includes conversion of TNT to 2,4,6-
trinitrobenzamides, nucleophilic substitution of an o-nitro
group by benzylthio group, cyclization of 2-benzylthio-
4,6-dinitrobenzamides to 4,6-dinitro-1,2-benzisothiazol-
3-ones and subsequent derivatization (alkylation, chlo-
rination, oxidation). Seventeen new heterocyclic com-
pounds have been synthesized.
Reaction of 4 with 50% H2O2 in glacial acetic acid at
65 °C gave 4,6-dinitro-1,2-benzisothiazol-3-one S-oxide
(23) in 60% yield. Further oxidation did not take place
even if the reaction mixture was heated at 100 °C for
several hours. However, we were able to prepare the 4,6-
dinitro-1,2-benzisothiazol-3-one S,S-dioxide (24) (“dinit-
rosaccharine”) in 53% yield by reaction of 4 with a
stronger oxidizer such as ammonium persulfate in con-
centrated H2SO4 (Scheme 6).
Exp er im en ta l Section
Gen er a l Meth od s. Compounds 1-3 were synthesized
according to known procedures.20
Sch em e 6
Ca u tion : Polynitroaromatic compounds are potential ex-
plosives. Proper protective measures (shields, glasses) should
(22) Davis, M. Benzisothiazoles. In Adv. Heterocycl. Chem.; Katritz-
ky, A. R., Boulton, A. J ., Eds.; Academic Press: New York, London,
1972; Vol. 3, p 43.
(23) To the best of our knowledge the mechanism of the formation
of 1,2-benzisothiazolones in the reaction of o-alkylsulfanylbenzamides
with halogenating agents has not been investigated yet. It is well
established that S-aryl-S-benzylsulfides easily react with chlorinating
agents with C-S bond cleavage to afford arylsulfanyl chlorides.21 It is
also known that 2-bromosulfanylbenzamide, that probably forms in
the reaction of S,S′-bis[2-(aminocarbonyl)phenyl] disulfide with bro-
mine, undergoes termal cyclization to 1,2-benzisothiazolone (A. Reis-
sert, E. Manns, Chem. Ber. 1928, 61, 1308). These facts as well as
literature data7,13,17 (one step conversion of 2-alkylsulfanylarylamides
to isothiazolones under the action of Cl2 or SO2Cl2) suggest that the
reaction includes transformation of 2-alkylsulfanyl-benzamides to
2-chlorosulfanylbenzamide followed by intramolecular cyclization of
the latter to the appropriate fused isothiazolone. A likely mechanism
for reaction of 2-benzylthio-nitrobenzamides with SO2Cl2 involves
substitution of the benzyl group by chlorine, followed by intramolecular
cyclization with the formation of the N-S bond. This mechanism could
explain why 2-methoxycarbonylmethylthio-4,6-dinitrobenzamide (1)
failed to react with SO2Cl2 compared to benzylthio derivative 3 since
benzyl group is a better leaving group.
Unlike 4, 2-methyl-4,6-dinitro-1,2-benzisothiazol-3-one
(11) reacts with 50% H2O2 in glacial acetic acid to afford
the S-oxide (25) or the S,S-dioxide (26), depending on the
reaction conditions (Scheme 7). When the reaction was
carried out at 50 °C, 25 was formed in 85% yield. On the
other hand, 2-methyl-4,6-dinitro-1,2-benzisothiazol-3-one-
S,S-dioxide (26) was prepared using boiling AcOH (118
°C). 4,6-Dinitro-2-phenyl-1,2-benzisothiazol-3-one (13)
reacted with 50% H2O2 at 100-110 °C to afford the
appropriate S,S-dioxide (27) in 54% yield.

8442 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
be used during experiments with these materials. Scale-up of
the reported reactions requires appropriate chemical hazards
testing.
C14H6N3F3O6S: C, 41.91; H, 1.51; N, 10.47; S, 7.99. Found:
C, 41.69; H, 1.45; N, 10.71; S, 7.70.
4-Ben zylsu lfon yl-6-n itr o-1,2-ben zisoth ia zol-3-on e (18).
To a solution of the mixture of 2-benzylsulfonyl-6-benzylthio-
4-nitrobenzamide (17) and 2-benzylsulfonyl-4-benzylthio-6-
nitrobenzamide (17a ) (1:1), prepared as described previously20
(1.8 g, 4.1 mmol), in CH2Cl2 (20 mL) was added SO2Cl2 (0.70
g, 0.40 mL, 5.2 mmol). The reaction mixture was stirred at 20
°C for 2 h. A yellow precipitate formed that was filtered,
washed successively with CH2Cl2 (2 × 5 mL), hexane (2 × 5
mL), and air-dried to afford 0.60 g (84% calculated based on
4,6-Din itr o-1,2-ben zisoth ia zol-3-on e (4). Meth od A. To
a stirred suspension of 2-methylthio-4,6-dinitrobenzamide (2)20
(0.50 g, 1.9 mmol) in absolute CH2Cl2 (10 mL) was added SO2-
Cl2 (0.30 mL, 0.50 g, 3.7 mmol). The reaction mixture, which
turned yellow immediately after the addition, was stirred at
15-20 °C for 2 h. A precipitate was filtered off, washed with
CH2Cl2 (2 × 3 mL), hexane (2 × 3 mL), and then air-dried to
afford 0.30 g (64%) of 4, bright-yellow crystals: dec ∼270 °C;
1
1
Rf 0.65 (CHCl3-acetone 5:1); H NMR (DMSO-d6) δ 8.69 (s,
17) of 18: mp 271-275 °C; Rf 0.32 (benzene-acetone 4:1); H
1H), 9.35 (s, 1H), very broad NH signal was not detected. Anal.
Calcd for C7H3N3O5S: C, 34.86; H, 1.25; N, 17.42; S, 13.29.
Found: C, 35.08; H, 1.34; N, 17.61; S, 13.05.
NMR (DMSO-d6) δ 5.12 (s, 2H), 7.30 (br.s, 5H), 8.47 (s, 1H),
9.40 (s, 1H), very broad NH signal was not detected. Anal.
Calcd for C14H10N2O5S2: C, 47.99; H, 2.88; N, 8.00; S, 18.30.
Found: C, 48.25; H, 3.01; N, 8.23; S, 18.08.
Meth od B. To a stirred suspension of 2-benzylthio-4,6-
dinitrobenzamide (3)20 (2.6 g, 7.8 mmol) in absolute CH2Cl2
(25 mL) was added SO2Cl2 (0.75 mL, 1.3 g, 9.3 mmol) at 20
°C. The mixture turned bright yellow immediately. It was
stirred for 1 h and diluted with hexane (15 mL). The precipi-
tate was filtered, washed with hexane (2 × 5 mL), and
air-dried to yield 1.84 g (98%) of 4. According to TLC and 1H
NMR spectra the compound was identical to 4 prepared by
method A.
3-Meth oxy-4,6-d in itr o-1,2-ben zisoth ia zole (19). To a
solution of 4,6-dinitro-1,2-benzisothiazol-3-one (4) (1.0 g, 4.2
mmol) in absolute DMF (15 mL) were added successively with
stirring K2CO3 (0.60 g, 4.4 mmol) and dimethylsulfate (0.40
mL, 0.53 g, 4.2 mmol). The reaction mixture was stirred at 20
°C for 6 h, and then poured into water (100 mL). The water
suspension was neutralized to pH∼6-7 using 10% HCl. A
precipitate was filtered, washed with water (2 × 10 mL), and
dried in air. The solid was extracted with boiling heptane (5
× 10 mL). On cooling, a precipitate formed that was collected
by filtration to yield 0.64 g (60%) of 19: mp 135-138 °C
(acetone-i-PrOH); Rf 0.53 (CCl4-acetone 4:1); 1H NMR (DMSO-
d6) δ 4.15 (s, 3H), 8.65 (s, 1H), 9.43 (s, 1H). Anal. Calcd for
C8H5N3O5S: C, 37.65; H, 1.97; N, 16.47; S, 12.56. Found: C,
37.84; H, 2.00; N, 16.32; S, 12.39.
A residue insoluble in boiling heptane was recrystallized
from CHCl3-i-PrOH mixture to yield 0.24 g (22%) of 2-methyl-
4,6-dinitro-1,2-benzisothiazol-3-one (11), yellow crystals: mp
231-235 °C. According to TLC and NMR 1H spectra, the
compound was identical to 11 prepared by reaction of N-meth-
yl-2-benzylthio-4,6-dinitrobenzamide (5) with SO2Cl2.
3-Ben zyloxy-4,6-d in itr o-1,2-ben zisoth ia zole (20). To a
solution of 4,6-dinitro-1,2-benzoisothiazol-3-one (4) (1.0 g, 4.2
mmol) in absolute DMF (15 mL) were added with stirring K2-
CO3 (0.70 g, 5.1 mmol) and then benzyl chloride (0.60 mL, 0.66
g, 5.2 mmol). The reaction mixture was stirred at 45-50 °C
for 5 h and poured into water (100 mL). The organic materials
were extracted with ether (3 × 3 mL), and the combined
organic layers were washed with water (2 mL) and then dried
over anhydrous MgSO4. The solvent was evaporated, and the
residue was extracted with boiling hexane (5 × 10 mL). The
hexane solution was cooled, and the precipitate was collected
by filtration to yield 0.60 g (44%) of 20: mp 135-136 °C;
Rf 0.75 (CHCl3); 1H NMR (DMSO-d6) δ 5.60 (s, 2H), 7.35-
7.50 (m, 5H), 8.80 (s, 1H), 9.45 (s, 1H). Anal. Calcd for
2-Su bstitu ted 4,6-Din itr o-1,2-ben zisoth iazol-3-on es 11-
16. Gen er a l P r oced u r e. To a stirred suspension of N-
substituted 2-benzylthio-4,6-dinitrobenzamide 5-10 contain-
ing ∼10% of the related 4-(benzylthio)derivative (5a -10a )20
(5.8 mmol) in absolute CH2Cl2 (30 mL) was added SO2Cl2 (0.50
mL, 0.83 g, 6.17 mmol). The reaction mixture was stirred for
2 h at 20 °C during which period a clear brown-yellow solution
formed. The solvent was evaporated in vacuo, and hexane (15
mL) was added to the solid residue. The precipitate was
filtered, washed with hexane (2 × 5 mL), and air-dried.
Recrystallization of the solid from i-PrOH (or its mixtures with
acetone or heptane) afforded analytically pure 2-substituted
4,6-dinitro-1,2-benzisothiazol-3-one (11-16).
2-Met h yl-4,6-d in it r o-1,2-b en zisot h ia zole-3-on e (11):
yellow crystals; 0.95 g (64%); mp 233-236 °C (i-PrOH-
1
acetone); Rf 0.06 (CCl4-acetone 4:1); H NMR (DMSO-d6): δ
3.42 (s, 3H), 8.55 (s, 1H), 9.25 (s, 1H). Anal. Calcd for
C8H5N3O5S: C, 37.65; H, 1.97; N, 16.47; S, 12.56. Found: C,
37.82; H, 2.06; N, 16.29; S, 12.31.
2-Ben zyl-4,6-d in it r o-1,2-b en zisot h ia zol-3-on e
(12):
yellow crystals; 1.74 g (91%); mp 172-175 °C (i-PrOH-CHCl3);
Rf 0.28 (CCl4-acetone 4:1); 1H NMR (DMSO-d6) δ 5.08 (s, 2H),
7.40 (br.s, 5H), 8.68 (s, 1H), 9.20 (s, 1H). Anal. Calcd for
C
14H9N3O5S: C, 50.76; H, 2.74; N, 12.68; S, 9.68. Found: C,
51.02; H, 2.85; N, 12.50; S, 9.37.
4,6-Din it r o-2-p h en yl-1,2-b en zisot h ia zol-3-on e
(13):
yellow crystals; 1.55 g (84%); mp 229-231 °C (i-PrOH-
acetone); Rf 0.24 (CCl4-acetone 4:1); 1H NMR (DMSO-d6) δ
7.45 (t, 1H, J ) 7.5 Hz), 7.58 (t, J ) 7.5 Hz, 2H), 7.68 (d, J )
7.5 Hz, 2H), 8.77 (s, 1H), 9.29 (s, 1H). Anal. Calcd for
C
14H9N3O5S: C, 50.76; H, 2.74; N, 12.68; S, 9.68. Found: C,
50.91; H, 2.80; N, 12.83; S, 9.44.
A residue insoluble in boiling hexane was recrystallized from
a CHCl3 - i-PrOH mixture to yield 0.20 g (15%) of 2-benzyl-
4,6-dinitro-1,2-benzisothiazol-3-one (12), yellow crystals: mp
172-175 °C. According to TLC and 1H NMR, the compound
was identical to 12 prepared by reaction of N-benzyl-2-
benzylthio-4,6-dinitrobenzamide (6) with SO2Cl2.
C
13H7N3O5S: C, 49.21; H, 2.22; N, 13.24; S, 10.10. Found: C,
49.02; H, 2.14; N, 13.41; S, 9.89.
2-(p -Br om op h en yl)-4,6-d in it r o-1,2-b en zisot h ia zol-3-
on e (14): bright yellow crystals; 1.26 g (55%); mp 196-199
°C (i-PrOH-acetone); Rf 0.72 (benzene-acetone 4:1); 1H NMR
(DMSO-d6): δ 7.65 (d, J ) 7.5 Hz, 2H), 7.71 (d, J ) 7.5 Hz,
2H), 8.65 (s, 1H), 9.30 (s, 1H). Anal. Calcd for C13H6N3BrO5S:
C, 39.41; H, 1.53; N, 10.61; Br, 20.17; S, 8.09. Found: C, 39.18;
H, 1.41; N, 10.85; Br, 19.79; S, 7.90.
2-[4′-(Ch lor od iflu or om eth oxy)p h en yl]-4,6-d in itr o-1,2-
ben zisoth ia zol-3-on e (15): yellow crystals; 1.83 g (76%); mp
128-131 °C (i-PrOH-heptane); Rf 0.70 (benzene-acetone 4:1);
1H NMR (DMSO-d6) δ 7.48 (d, J ) 8.5 Hz, 2H), 7.83 (d, J )
8.5 Hz, 2H), 8.64 (s, 1H), 9.33 (s, 1H). Anal. Calcd for C14H6N3-
ClF2O6S: C, 40.25; H, 1.45; N, 10.06; S, 7.67. Found: C, 40.03;
H, 1.39; N, 10.28; S, 7.42.
(4,6-Din itr o-1,2-ben zisoth iazol-3-yl)oxyacetic Acid Eth -
yl Ester (21). A mixture of 4,6-dinitro-1,2-benzisothiazol-3-
one (4) (1.0 g, 4.2 mmol), ethyl chloroacetate (0.50 mL, 0.58 g,
4.7 mmol), K2CO3 (0.58 g, 4.2 mmol), and dry DMF (15 mL)
was stirred at 40-45 °C for 8 h and then kept at 12 °C
overnight. The mixture was poured into water (100 mL) and
extracted with ether (5 × 30 mL). The combined ether extracts
were dried over anhydrous MgSO4, the solvent was evaporated
in vacuo, and the residue was extracted with boiling hexane
(5 × 20 mL). A precipitate formed on cooling, which was
filtered, washed with hexane, and air-dried to afford 0.60 g
(44%) of 21: yellow crystals; mp 117-120 °C; Rf 0.42 (benzene);
1H NMR (DMSO-d6) δ 1.25 (t, J ) 7.0 Hz, 3H), 4.20 (q, J )
7.0 Hz, 2H), 5.10 (s, 2H), 8.70 (s, 1H), 9.47 (s, 1H). Anal. Calcd
for C11H9N3O7S: C, 40.37; H, 2.77; N, 12.84; S, 9.80. Found:
C, 40.56; H, 2.84; N, 13.01; S, 9.67.
2-(4′-Tr iflu or om et h oxyp h en yl)-4,6-d in it r o-1,2-b en z-
isoth ia zol-3-on e (16): yellow crystals; 1.69 g (76%); mp 150-
153 °C (i-PrOH-heptane); Rf 0.80 (benzene-acetone 4:1);
1H NMR (DMSO-d6) δ 7.58 (d, J ) 8.5 Hz, 2H), 7.83 (d, J )
8.5 Hz, 2H), 8.77 (s, 1H), 9.29 (s, 1H). Anal. Calcd for

Synthetic Utilization of Polynitroaromatic Compounds. 2
J . Org. Chem., Vol. 65, No. 25, 2000 8443
3-Ch lor o-4,6-d in itr o-1,2-ben zisoth ia zole (22). A mixture
of 4,6-dinitro-1,2-benzisothiazol-3-one (4) (1.0 g, 4.2 mmol),
PCl5 (5.0 g, 24 mmol), and POCl3 (1 mL) was heated at 150 °C
for 20 h. Excess quantities of PCl5 and POCl3 were destroyed
by addition of ice (∼100 g). Organic materials were extracted
with CHCl3 (2 × 50 mL). The combined organic extracts were
washed with water (2 × 20 mL), dried over anhydrous MgSO4,
and filtered. Evaporation of the solvent and crystallization of
the residue from i-PrOH afforded 0.70 g (65%) of 22: mp 127-
129 °C; Rf 0.41 (CCl4-acetone 4:1); 1H NMR (DMSO-d6) δ 8.94
(s, 1H), 9.62 (s, 1H). Anal. Calcd for C7H2N3ClO4S: C, 32.38;
H, 0.78; N, 16.19; C1, 13.66; S, 12.35. Found: C, 32.17; H, 0.82;
N, 15.99; Cl, 13.84; S, 12.17. After the submission of the
manuscript a compound described as 3-chloro-4,6-dinitroben-
zo[d]isothiazole (from 2,4,6-trinitrobenzonitrile) was reported
elsewhere (Dalinger, I. L.; Cherkasova, T. I.; Khutoretskii, V.
M.; Shevelev, S. A. Mendeleev Comm. 2000, 72). However, mp
and 1H NMR of this compound are significantly different
compared to our data.
(s, 3H), 9.18 (s, 1H), 9.41 (s, 1H); MS (m/z, I) 271 (M+, 24),
194 (M+ - CH3-NdSdO, 100), 148 (M+ - CH3NdSdO - NO2,
31), 120 (M+ - CH3NdSdO - NO2 -CO, 50); IR spectra (ν,
cm-1) 3090, 3000, 2940, 2890 (CH), 1705 (CdO), 1610, 1545
(NO2), 1360 (NO2), 1320, 1140 (S-O). Anal. Calcd for
C8H5N3O6S: C, 35.43; H, 1.86; N, 15.49; S, 11.82. Found: C,
35.60; H, 1.94; N, 15.63; S, 11.62.
2-Meth yl-4,6-d in itr o-1,2-ben zisoth ia zol-3-on e S,S-Di-
oxid e (26). A mixture of 2-methyl-4,6-dinitro-1,2-benzisothia-
zol-3-one (11) (0.47 g, 1.8 mmol), 50% H2O2 (1.0 mL), and
glacial acetic acid (6 mL) was refluxed for 3 h. The solvent
was evaporated in vacuo, water (5 mL) was added to a residue,
a precipitate was filtered and washed with water (2 mL), dried
in the air, and recrystallized from acetone-i-PrOH mixture
to yield 0.15 g (28%) of 26: colorless solid; mp 240-243 °C; Rf
1
0.28 (CCl4-acetone 4:1); H NMR (DMSO-d6) δ 3.25 (s, 3H),
9.22 (s, 1H), 9.50 (s, 1H). Anal. Calcd for C8H5N3O7S: C, 33.46;
H, 1.75; N, 14.63; S, 11.16. Found: C, 33.68; H, 1.83; N, 14.48;
S, 10.97.
4,6-Din itr o-1,2-ben zisoth ia zol-3-on e S-Oxid e (23). To a
stirred suspension of 4,6-dinitro-1,2-benzisothiazol-3-one (4)
(0.20 g, 0.83 mmol) in glacial acetic acid (1 mL) was added
50% H2O2 (1 mL). The reaction mixture was stirred at 65 °C
for 3 h. After cooling, a precipitate was filtered, washed with
water, and air-dried to yield 0.13 g (60%) of 23: pale-yellow
solid; mp 262-263 °C; Rf 0.26 (CHCl3-acetone 5:1); 1H NMR
(DMSO-d6) δ 9.13 (s, 1H), 9.35 (s, 1H); MS (m/z, I) 257 (M+,
4,6-Din itr o-2-p h en yl-1,2-ben zisoth ia zol-3-on e S,S-Di-
oxid e (27). A mixture of 4,6-dinitro-2-phenyl-1,2-benzisothia-
zol-3-one (13) (0.50 g, 1.6 mmol), 50% H2O2 (2.0 mL) and glacial
AcOH (10 mL) was heated at 100 °C for 2 h. The starting
compound (13) was dissolved completely followed by formation
of a colorless precipitate. The reaction mixture was cooled to
20 °C for 12 h. The resulting precipitate was filtered, washed
with water (2 × 5 mL), and air-dried to yield 0.30 g (54%) of
10), 211 (M+ - NO2, 13), 194 (M+ - HNSO, 38), 148 (M+
-
1
27: dec 250 °C; Rf 0.41(benzene); H NMR (DMSO-d6) δ 7.60
HNSO - NO2, 18), 74 (S-NdCdO, 100). Anal. Calcd for
C7H3N3O6S: C, 32.69; H, 1.18; N, 16.34; S, 12.47. Found: C,
32.84; H, 1.13; N, 16.18; S, 12.30.
(m, 2H),7.68 (m, 3H), 9.35 (s, 1H), 9.68 (s, 1H); MS (m/z, I)
349 (M+, 42), 119 (PhNCO, 35), 91 (PhN, 100), 74 (C6H2, 93),
64 (SO2, 66). Anal. Calcd for C13H7N3O7S: C, 44.70; H, 2.02;
N, 12.03; S, 9.18. Found: C, 44.89; H, 1.97; N, 11.92; S, 8.98.
4,6-Din itr o-1,2-ben zisoth ia zol-3-on e S,S-Dioxid e (24).
A suspension of 4,6-dinitro-l,2-benzisothiazol-3-one (4) (0.15
g, 0.62 mmol) and (NH4)2S2O8 (0.57 g, 2.5 mmol) in 95% H2-
SO4 (2 mL) was stirred at 20 °C for 16 h. The reaction mixture
was poured on ice (∼20 g) and extracted with ethyl acetate
(5 × 5 mL), and the combined organic layers were washed with
water (3 × 2 mL) and dried over anhydrous MgSO4. Evapora-
tion of the solvent and recrystallization of the residue from
an i-PrOH-hexane mixture afforded 0.09 g (53%) of 24:
colorless crystals; mp 267-270 °C dec; Rf 0.13 (CHCl3-acetone
5:1); 1H (DMSO-d6) δ 8.70 (s, 1H), 8.92 (s, 1H); MS (m/z, I)
273 (M+, 20), 209 (M+ - SO2, 28), 74 (S-NdCdO, 100). Anal.
Calcd for C7H3N3O7S: C, 30.78; H, 1.11; N, 15.38; S, 11.74.
Found: C, 30.59; H, 1.06; N, 15.52; S, 11.57.
2-Meth yl-4,6-d in itr o-1,2-ben zisoth ia zol-3-on e S-Oxid e
(25). To a stirred suspension of 2-methyl-4,6-dinitro-1,2-
benzisothiazole-3-one (11) (0.43 g, 1.69 mmol) in glacial acetic
acid (9 mL) was added 50% H2O2 (0.6 mL). The reaction
mixture was stirred at 50 °C for 6 h. After cooling, a precipitate
was filtered, washed with AcOH (2 × 2 mL), water (2 mL),
dried in the air, and recrystallized from an acetone-i-PrOH
mixture to yield 0.39 g (85%) of 25: pale yellow solid; mp 205-
206 °C; Rf 0.09 (CCl4-acetone 4:1); 1H NMR (DMSO-d6) δ 3.32
3,5-Din itr o-2-(m eth oxycar bon yl)ben zen esu lfam ide (28).
A mixture of 3-methoxy-4,6-dinitro-1,2-benzisothiazole (19)
(0.20 g, 0.80 mmol), 50% H2O2 (2.0 mL), and glacial acetic acid
(10 mL) was heated at 90-100 °C for 2 h. The solvent was
evaporated in vacuo, water (3 mL) was added to the residue,
and the precipitate was filtered, washed with water (2 × 5
mL), and air-dried to yield 0.20 g (84%) of 28: mp 170-174
1
°C; H NMR (DMSO-d6) δ 3.96 (s, 3H), 8.00 (s, 2H), 9.00 (s,
1H), 9.10 (s, 1H); MS (m/z, I) 305 (M+, 3), 289 (M+ - O, 17),
275 (M+ - O - CH2, 21), 274 (M+ - O - NH, 100), 228 (M+
-
O - NH - NO2, 26). Anal. Calcd for C8H7N3O8S: C, 31.48; H,
2.31; N, 13.77; S, 10.50. Found: C, 31.71; H, 2.39; N, 13.63; S,
10.35.
Ack n ow led gm en t. The research was sponsored by
the IPP program, U.S. Department of Energy under
contract DE-AC05-00OR22725 with Oak Ridge National
Laboratory, managed and operated by UT-Battelle,
LLC.
J O000480C