Reactions of 1,3-dihydrobenzo[c]thiophene 2,2-dioxides with electrophilic agents

Article abstract of DOI:10.1007/s11172-005-0269-5

Nitration, sulfonation, and iodination of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and its derivatives with electron-releasing and electron-withdrawing substituents were studied. Electrophilic substitution in 1,3-dihydrobenzo[c] thiophene 2,2-dioxide occurs at position 5. The presence of electron-withdrawing substituents in this position hinders further substitution, while electron-releasing substituents in positions 5 and 6 direct an electrophile to position 4.

Full text of DOI:10.1007/s11172-005-0269-5

Russian Chemical Bulletin, International Edition, Vol. 54, No. 2, pp. 437—440, February, 2005
437
Reactions of 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxides
with electrophilic agents
G. A. Tashbaev
Gulistan State University,
4th mikroraion, 707000 Gulistan, Uzbekistan Republic.
Eꢀmail: tgabek@yandex.ru
Nitration, sulfonation, and iodination of 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide and
its derivatives with electronꢀreleasing and electronꢀwithdrawing substituents were studied.
Electrophilic substitution in 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide occurs at position 5.
The presence of electronꢀwithdrawing substituents in this position hinders further substitution,
while electronꢀreleasing substituents in positions 5 and 6 direct an electrophile to position 4.
Key words: 1,3ꢀdihydrobenzo[c]thiophene, 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxides,
nitration, sulfonation, halogenation.
Scheme 1
Reactivity of 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdiꢀ
oxide and its derivatives is of great interest, because they
are successfully used in organic synthesis, in particular,
for syntheses of physiologically active compounds and
pesticides.
To extend the synthetic potential of these compounds,
it seems promising to use their functionalization by subꢀ
stitution of hydrogen atoms of the benzene ring and hetꢀ
erocyclic moiety and reactions of the sulfono group.
In this work, we studied the benzene ring substitution
of 1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxides by differꢀ
ent electrophilic agents.
Nitration. We used unsubstituted 1,3ꢀdihydrobenꢀ
zo[c]thiophene 2,2ꢀdioxide (1), 5,6ꢀdimethylꢀ1,3ꢀdiꢀ
hydrobenzo[c]thiophene 2,2ꢀdioxide (2), 5,6ꢀethyleneꢀ
dioxyꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (3), and
5ꢀnitroꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (4) as
substrates.
Sulfone 1 has previously1 been nitrated with fuming
nitric acid to obtain nitro derivative 4 in moderate
yield (55%). We developed conditions for the preparative
synthesis of the latter by the action of fuming HNO3 in
a medium of 1 : 1 AcOH—Ac2O mixture (10 °С, 5 h).
As a result, compound 4 was obtained in high yield
(81.2%), and its constants correspond to literature values1
(Scheme 1).
The IR spectrum of compound 4 contains absorption
bands at 1540 and 1360 cm–1, confirming the presence of
a nitro group. The direction of nitration to position 5 of
the heterocycle was also confirmed by the 1H NMR specꢀ
trum of 5ꢀaminoꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdiꢀ
oxide (5), which is the reduction product of nitro derivaꢀ
tive 4 with tin in hydrochloric acid. The structure of amine
5 was proved by the IR and 1H NMR spectral data. Its IR
spectrum contains the characteristic absorption bands of
1
the SO2 group (1345 cm–1). The H NMR spectrum exꢀ
hibits signals of protons of the methylene group of the
heterocycle (δ 4.20 and 4.27) and amino group (δ 5.17).
The signals of aromatic protons at δ 6.45 (s), 6.52 (d), and
6.95 (d) indicate that the amino group is in position 5.
Our attempt to introduce the second nitro group by
the action of concentrated HNO3 in Ac2O and H2SO4
was unsuccessful, probably, because of the deactivating
effect of the introduced nitro group on the benzene ring.
We have previously2 studied the reaction of 5,6ꢀdiꢀ
methylꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (2)
with nitric acid under different conditions. When benzoꢀ
thiophene dioxide 2 is treated with fuming HNO3 or a
mixture of HNO3 and AcOH (1 : 5), or HNO3 and H2SO4
(1 : 5), 5,6ꢀdimethylꢀ4ꢀnitroꢀ1,3ꢀdihydrobenzo[c]thioꢀ
phene 2,2ꢀdioxide (6) is formed (Scheme 2). The reacꢀ
tion of compound 2 with fuming HNO3 in the presence of
Ac2O produces only resinification products.
The reduction of compound 6 with tin in hydrochloric
acid affords 4ꢀaminoꢀ5,6ꢀdimethylꢀ1,3ꢀdihydrobenꢀ
zo[c]thiophene 2,2ꢀdioxide (7) in good yield. The strucꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 428—431, February, 2005.
1066ꢀ5285/05/5402ꢀ0437 © 2005 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
G. A. Tashbaev
Scheme 2
chlorosulfonic acid occurs under milder conditions. For
example, when a threefold excess of ClSO3H is used in
H2SO4 at 100 °С, 5,6ꢀdimethylꢀ1,3ꢀdihydrobenzo[c]thioꢀ
pheneꢀ4ꢀsulfochloride 2,2ꢀdioxide (10) is formed in high
yield (Scheme 4).
Scheme 4
Halogenation. The chlorination and bromination of
benzothiophene 1 in the presence of iron compounds
were unsuccessful. The reaction of benzothiophene 1
with iodine in the presence of silver sulfate afforded
5ꢀiodoꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (11)
in high yield, and its constants agree with literature data4
(Scheme 5).
R = Me (2, 6); R + R = —OCH2CH2O— (3, 8)
tures of nitro compound 6 and amine 7 were confirmed
by data of the IR spectra.
It is known that the introduction of strong electronꢀ
releasing substituents (amino, hydroxy, and alkoxy groups)
into the benzene ring enhances the reactivity of the molꢀ
ecule toward electrophilic agents. Therefore, we chose
ethylenedioxy derivative 3 as an object.
Scheme 5
As expected, compound 3 was successfully nitrated
under mild conditions: with dilute nitric acid using slight
heating. As a result, 5,6ꢀethylenedioxyꢀ4ꢀnitroꢀ1,3ꢀ
dihydrobenzo[c]thiophene 2,2ꢀdioxide (8) was obtained
in good yield (see Scheme 2). The structure of compound
8 was confirmed by the data of its IR spectrum, which
exhibits intense absorption bands at 1360 and 1530 cm–1
characteristic of the nitro group and bands at 1150 and
1330 cm–1 corresponding to the sulfono group.
Sulfonation. We studied the reactions of sulfones 1
and 2 with chlorosulfonic acid in a medium of the acid
itself taken in a fivefold excess at 120—125 °С. As a result,
1,3ꢀdihydrobenzo[c]thiopheneꢀ5ꢀsulfochloride 2,2ꢀdioxꢀ
ide (9)3 was obtained in high yield (Scheme 3).
The structure of derivative 11 was confirmed by the
IR spectrum containing absorption bands at 820 and
900 cm–1 characteristic of the substituted benzene ring
and intense bands at 1155 and 1320 cm–1 caused by the
sulfono group. The absorption bands at 1455—1470 cm–1
can be assigned to vibrations of the methylene group of
the heterocycle, and the absorption band of the C—I
bond appears at 660 cm–1
.
Thus, electrophilic substitution in 1,3ꢀdihydrobenꢀ
zo[c]thiophene 2,2ꢀdioxide (1) occurs at position 5 of the
heterocycle, while the substitution occurs at position 4 in
the case of its 5,6ꢀdisubstituted derivatives.
Scheme 3
Experimental
IR spectra were recorded on a URꢀ20 spectrometer in KBr
1
pellets. H NMR spectra were obtained on a Tesla BSꢀ487 inꢀ
The IR spectrum of compound 9 contains absorption
bands of the sulfono group (1130 and 1325 cm–1), aroꢀ
matic ring (870 and 1580 cm–1), and chlorosulfonyl group
strument (80 MHz) using hexamethyldisiloxane as internal stanꢀ
dard and acetoneꢀd6 as solvent. Reactions and purity of syntheꢀ
sized compounds were monitored by TLC on Silufol plates
(iodine vapor detection). Melting points were determined on a
Boetius heating microstage.
1,3ꢀDihydrobenzo[c]thiophene. A mixture of α,α´ꢀdibromoꢀ
оꢀxylene5 (132 g, 0.5 mol) and benzene (500 mL) was stirred
until the dibromide dissolved completely. Then a solution of
sodium sulfide nonahydrate (240 g, 1 mol) in water (200 mL)
1
(1320 cm–1). The H NMR spectrum exhibits signals of
protons of the methylene group (δ 4.76) and H(4), H(6)
(δ 7.93 and 7.88), and H(7) protons (δ 7.63) of the aroꢀ
matic fragment.
The presence of two Me groups in sulfone 2 enhances
the reactivity of the molecule, and its reaction with

1,3ꢀDihydrobenzo[c]thiophene 2,2ꢀdioxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
439
and benzyltriethylammonium chloride (0.5 g) were added to the
mixture. The reaction mixture was stirred for 30 h at ~20 °C.
After the end of the reaction, the mixture was distilled with
water vapor. Benzene was distilled off first, and then the sulfide
was collected under a water layer. The resulting sulfide was
separated and cooled in a refrigerator. The yield of the product
was 41—45 g (60.3—66.1%), m.p. 25—26 °С (cf. Ref. 6:
22.5—23.5 °С). The product was used without additional purifiꢀ
cation. 1H NMR, δ: 4.46 (s, 4 Н, СН2); 7.14 (s, 4 Н, СН).
1,3ꢀDihydrobenzo[c]thiophene 2,2ꢀdioxide (1). A mixture of
1,3ꢀdihydrobenzo[c]thiophene (40.8 g, 0.03 mol) and glacial
AcOH (250 mL) was cooled in an ice bath at 5—10 °C, and a
30% solution of H2O2 (70 mL) was added dropwise for 1 h. Then
the mixture was stirred for 1 h at ~20 °C and for 3 h at 90—95 °С.
After the end of the reaction, the mixture was cooled, and preꢀ
cipitated crystals were filtered off, washed with water, dried in
air, and recrystallized from EtOH. The yield of compound 1 was
45.1 g (89.5%), m.p. 152—153 °С (cf. Ref. 6: 150—151 °С). IR,
ν/cm–1: 1140, 1320 (SO2). 1H NMR, δ: 4.37 (s, 4 Н, СН2); 7.25
(s, 4 Н, СН).
precipitate that formed was filtered off, treated as the major
product, and dried in air. The product was recrystallized
from AcOH. The yield of sulfone 4 was 34.6 g (81.2%), m.p.
169—170 °С (cf. Ref. 1: 167—169 °С). IR, ν/cm–1: 725, 955
(arom.); 1140, 1320 (SO2); 1360, 1540 (NO2).
5ꢀAminoꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (5).
Hydrochloric acid (120 mL) was added dropwise for 1 h to
sulfone 4 (21.3 g, 0.1 mol), tin (21 g), and refluxing EtOH
(500 mL). Then the mixture was refluxed for 8 h, cooled, and
neutralized to a weakly alkaline reaction. A precipitate was sepaꢀ
rated and dried. The solid powdered product was extracted with
chloroform and dried with anhydrous MgSO4. The solvent was
distilled off, and the residue was recrystallized from EtOH. The
yield of amino derivative 5 was 14.9 g (81.4%), m.p. 199—201 °С
1
(cf. Ref. 1: 194—196 °С). H NMR, δ: 4.20, 4.27 (both s, 4 Н,
СН2); 5.17 (s, 2 Н, NH2); 6.45 (s, 1 H, H(4)); 6.52, 6.95 (both t,
2 H, H(6), H(7), J = 7 Hz). IR, ν/cm–1: 1345 (SO2); 3490 (NН2).
5,6ꢀDimethylꢀ4ꢀnitroꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdiꢀ
oxide (6) was synthesized similarly to a described procedure2 in
82.9% yield, m.p. 170—171 °С.
5,6ꢀDimethylꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (2)
was synthesized by a known procedure2 in 90.0% yield, colorless
needles, m.p. 172—173 °С. IR, ν/cm–1: 720, 930, 1500 (arom.);
1100 (Me); 1140, 1320 (SO2).
4ꢀAminoꢀ5,6ꢀdimethylꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdiꢀ
oxide (7). A mixture of nitro derivative 6 (1 g), tin (1 g), and
concentrated hydrochloric acid (5 mL) was carefully heated in a
water bath for 1 h to 80 °С. Then the mixture was stored at this
temperature for 1 h, cooled, and neutralized with a 25% solution
of potash. A precipitate was separated and dried. The solid powꢀ
dered product was extracted with chloroform (4×30 mL), and
the extracts were combined and dried with anhydrous MgSO4.
The solvent was distilled off, and the residue was recrystallized
from EtOH. The yield of compound 7 was 0.35 g (40.0%), m.p.
195—196 °С. IR, ν/cm–1: 1140, 1310 (SO2); 3320 (NН2).
5,6ꢀEthylenedioxyꢀ4ꢀnitroꢀ1,3ꢀdihydrobenzo[c]thiophene
2,2ꢀdioxide (8). A mixture of HNO3 (2.5 mL), water (2.5 mL),
and sulfone 3 (0.226 g) was stirred first for 2 h at ~20 °C and
then for 3 h at 60 °С. After the end of the reaction, the mixture
was poured into a glass filled with ice (25 g). A precipitate was
separated, dried, and recrystallized from formic acid. The yield
of compound 8 was 0.228 g (84%), m.p. 231—233 °С, Rf 0.38
(benzene). Found (%): С, 44.37; Н, 3.24; N, 5.10. C10H9NO6S.
Calculated (%): С, 44.28; Н, 3.34; N, 5.16. IR, ν/cm–1: 1150,
1330 (SО2); 1445 (СН2); 1360, 1530 (NО2).
5,6ꢀEthylenedioxyꢀ1,3ꢀdihydrobenzo[c]thiophene. 6,7ꢀBisꢀ
chloromethylꢀ1,4ꢀbenzodioxane7 (4.66 g, 0.02 mol) was added
at 35—40 °С by portions with stirring in a nitrogen flow to a
mixture of sodium sulfide nonahydrate (6.0 g, 0.025 mol), EtOH
(200 mL), and water (40.0 mL). Then the mixture was stirred for
2 h at 60 °С, cooled to ~20 °C, and filtered. The filtrate was
concentrated in a nitrogen flow, and the residue was dissolved in
benzene (50 mL), washed with water, and dried with anhydrous
MgSO4. A benzene solution was filtered off, the solvent was
evaporated, and the residue was recrystallized from MeOH. The
yield of the product was 1.0 g (25%), m.p. 81—82 °С (cf. Ref. 8:
m.p. 80—82 °С), Rf 0.63 (benzene). Found (%): С, 61.45;
Н, 5.07; S, 17.30. C10H10O2S. Calculated (%): С, 61.94; Н, 5.19;
S, 16.50. 1H NMR, δ: 4.06 (s, 4 Н, СН2); 4.16 (s, 4 Н, СН2О);
6.70 (s, 2 H, СH).
5,6ꢀEthylenedioxyꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide
(3). 28% Hydrogen peroxide (5 mL) was added with stirring at
30 °С to 5,6ꢀethylenedioxyꢀ1,3ꢀdihydrobenzo[c]thiophene
(1.0 g, 0.005 mol) in glacial AcOH (15 mL). Then the reaction
mixture was stirred for 8 h at 80 °С. After the end of the reacꢀ
tion, the contents of the flask was poured into a glass containing
a mixture of ice and water, and the precipitate that formed was
filtered off, dried, and recrystallized from EtOH. The yield of
sulfone 3 was 0.92 g (90%), m.p. 220—222 °С (cf. Ref. 8:
220—221 °С), Rf 0.65 (benzene—acetone, 5 : 1). Found (%):
C, 53.10; H, 4.75; S, 14.33. C10H10O4S. Calculated (%):
C, 53.10; H, 4.42; S, 14.16. IR, ν/cm–1: 1140, 1310 (SO2).
5ꢀNitroꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (4). Niꢀ
tric acid (40 mL, d = 1.50) was added dropwise at –5—–10 °С
with stirring for 30 min to compound 1 (33.6 g, 0.2 mol) and a
mixture of Ac2O and AcOH (1 : 1) (240 mL). Stirring was
continued for 5—8 h. During this time, sulfone was completely
dissolved, a transparent solution formed, and then crystals preꢀ
cipitated. After the end of the reaction, the precipitate was filꢀ
tered off on the Büchner funnel, washed with water and a dilute
soda solution to the neutral reaction and again with water, and
dried. Iceꢀcold water (500 mL) was added to the filtrate, and the
1,3ꢀDihydrobenzo[c]thiopheneꢀ5ꢀsulfochloride 2,2ꢀdioxide
(9) was synthesized similarly to a known procedure3 in 70.0%
1
yield, m.p. 164—165 °С. H NMR, δ: 4.76 (s, 4 Н, СН2); 7.63,
7.88, 7.93 (all s, 3 H, СН).
5,6ꢀDimethylꢀ1,3ꢀdihydrobenzo[c]thiopheneꢀ4ꢀsulfochloride
2,2ꢀdioxide (10). Sulfone 2 (2 g, 0.01 mol) was dissolved in
concentrated H2SO4 (10 mL), and freshly distilled chlorosulfonic
acid (2.4 mL, 0.03 mol) was added with stirring. The mixture
was stirred for 4 h at 100 °С and poured into a glass with iceꢀcold
water (100 mL). A precipitate was separated and dried. The
product was recrystallized from AcOH. The yield of compound
10 was 1.65 g (56%), m.p. 120—122 °С. Found (%): С, 41.10;
Н, 3.45; S, 21.15. C10H11ClO4S2. Calculated (%): С, 40.75;
Н, 3.76; S, 21.75. IR, ν/cm–1: 870, 910, 1580 (arom.); 1140,
1320, 1325 (SО2, SО2Сl).
5ꢀIodoꢀ1,3ꢀdihydrobenzo[c]thiophene 2,2ꢀdioxide (11).
A mixture was concentrated H2SO4 (20 mL), sulfone 1 (1.68 g,
0.01 mol), molecular iodine (6.35 g, 0.025 mol), and silver sulꢀ
fate (1.55 g) was stirred for 32 h at 30—40 °С. Then the resulting
mixture was poured into a glass with iceꢀcold water (50 mL),

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G. A. Tashbaev
and a precipitate was separated, washed with water, dried, and
recrystallized from EtOH. The yield of compound 11 was 1.8 g
(65%), m.p. 120—122 °С. Found (%): С, 32.43; Н, 2.51;
S, 11.05. C8H7IO2S. Calculated (%): С, 32.67; Н, 2.40; S, 10.90.
IR, ν/cm–1: 820, 900 (arom.); 1155, 1320, 1320 (SО2);
1455 (CH2).
[Bulletin of Academy of Sciences of Tadjik Republic, Departꢀ
ment of Physical, Mathematical, Chemical, and Geological Sciꢀ
ences], 1987, No. 1, 41 (in Russian).
4. W. Oppolzer and A. Roberts, Helv. Chim. Acta, 1980, 63, 1703.
5. Organic Synthesis, Ed. W. S. Johnson, J. Wiley and Sons, New
York—London, 1954, 34.
6. J. A. Oliver and P. H. Ongley, Chem. Ind., 1965, 25, 1024.
7. A. E. Agronomov and Yu. S. Shabarov, Laboratornye Raboty v
Organicheskom Praktikume [Laboratory Practical Works in Orꢀ
ganic Chemistry], Khimiya, Moscow, 1974, 178 (in Russian).
8. G. A. Tashbaev, I. M. Nasyrov, and S. S. Dzhalolov, Dokl.
Akad. Nauk Tadzh. SSR [Reports of Academy of Sciences of
Tadjik Republic], 1982, 25, 732 (in Russian).
References
1. B. Iddon, Adv. Heterocycl. Chem., 1972, 14, 331.
2. G. A. Tashbaev and I. M. Nasyrov, Izv. Akad. Nauk Tadzh.
SSR. Otd. Fiz.ꢀMat., Khim. i Geol. Nauk [Bulletin of Academy
of Sciences of Tadjik Republic, Department of Physical, Mathꢀ
ematical, Chemical, and Geological Sciences], 1987, No. 3, 54
(in Russian).
3. G. A. Tashbaev, S. S. Dzhalolov, and I. M. Nasyrov, Izv.
Akad. Nauk Tadzh. SSR. Otd. Fiz.ꢀMat., Khim. i Geol. Nauk
Received May 26, 2003;
in revised form January 13, 2004