Synthesis of 1,3-benzothiazol-2(3H)-one and some its derivatives

Article abstract of DOI:10.1134/S107042801109020X

Acylation of 2-aminobenzenethiol with methyl chloroformate in pyridine gave dimethyl 2,2′-disulfanediylbis( 2,1-phenylene)dicarbamate instead of expected methyl 2-suylfanylphenylcarbamate. Heating of the product with zinc dust in glacial acetic acid led to the formation of 1,3-benzothiazol-2(3H)-one. Alkylation of the latter with 1,2-dibromoethane and allyl bromide, as well as acylation with chloroacetyl chloride, afforded the corresponding 3-substituted derivatives. 3-[3-(Pyridin-2-yl)-4,5-dihydroisoxazol-5-ylmethyl]-1,3- benzothiazol-2(3H)-one was synthesized with high regioselectivity by 1,3-dipolar cycloaddition of 3-allyl-1,3-benzothiazol-2(3H)-one to pyridine-2-carbonitrile oxide generated from N-hydroxypyridine-2-carboximidoyl chloride hydrochloride by the action of triethylamine. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S107042801109020X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1375–1379. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.V. Velikorodov, A.K. Kuanchalieva, E.A. Melent’eva, O.L. Titova, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 9, pp. 1353–1356.
Synthesis of 1,3-Benzothiazol-2(3H)-one and Some Its Derivatives
A. V. Velikorodov, A. K. Kuanchalieva, E. A. Melent’eva, and O. L. Titova
Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia
e-mail: avelikorodov@mail.ru
Received March 20, 2010
Abstract—Acylation of 2-aminobenzenethiol with methyl chloroformate in pyridine gave dimethyl 2,2′-di-
sulfanediylbis(2,1-phenylene)dicarbamate instead of expected methyl 2-suylfanylphenylcarbamate. Heating of
the product with zinc dust in glacial acetic acid led to the formation of 1,3-benzothiazol-2(3H)-one. Alkylation
of the latter with 1,2-dibromoethane and allyl bromide, as well as acylation with chloroacetyl chloride, afforded
the corresponding 3-substituted derivatives. 3-[3-(Pyridin-2-yl)-4,5-dihydroisoxazol-5-ylmethyl]-1,3-benzo-
thiazol-2(3H)-one was synthesized with high regioselectivity by 1,3-dipolar cycloaddition of 3-allyl-1,3-benzo-
thiazol-2(3H)-one to pyridine-2-carbonitrile oxide generated from N-hydroxypyridine-2-carboximidoyl
chloride hydrochloride by the action of triethylamine.
DOI: 10.1134/S107042801109020X
Derivatives of 2-aminobenzenethiol are widely
used in the synthesis of heterocyclic compounds [1, 2].
Acylation of 2-aminobenzenethiol is not selective, and
the reaction direction depends on the conditions and
the nature of acylating agent. It is known that acylation
of 2-aminobenzenethiol with acid chlorides in the pres-
ence of bases yields 2-substituted 1,3-benzothiazoles
[3] and that the reaction with chloroacetyl chloride in
methylene chloride occurs exclusively at the nitrogen
atom [4]. Acylation of 2-aminobenzenethiol with
acetic and propionic anhydrides in aqueous medium in
the presence of sodium hydrogen carbonate was ac-
companied by formation of 2-methyl- and 2-ethyl-1,3-
benzothiazoles, respectively (in addition to the corre-
sponding N-acyl derivatives) [5]. Ethyl 3-(4-oxo-
2,3,4,5-tetrahydro-1,5-benzothiazepin-5-yl)propionate
or N-[2-(carboxyethylsulfanyl)phenyl]-β-alanine were
formed in the reaction of acrylic acid with 2-amino-
benzenethiol, depending on the reactant ratio [6].
We found that acylation of 2-aminobenzenethiol
with methyl chloroformate in anhydrous pyridine gives
dimethyl 2,2′-disulfanediylbis(2,1-phenylene)dicarba-
mate (I) instead of expected methyl 2-suylfanylphenyl-
carbamate (Scheme 1). Compound I was synthesized
previously by acylation of 2,2′-disulfanediyldianiline
with methyl chloroformate [7].
The structure of disulfide I was confirmed by the
1
IR, H NMR, and mass spectra. The IR spectrum of I
lacked absorption band at 2550 cm–1, which is typical
of stretching vibrations of SH group but contained ab-
sorption bands at 3380 and 1740 cm–1 due to stretching
vibrations of NH and C=O groups in addition to ab-
sorption bands corresponding to vibrations of the ben-
zene ring. No SH signal (δ 3.27 ppm [8]) was observed
in the 1H NMR spectrum of I. In the mass spectrum of
compound I, ion peaks with m/z 364 [M]+ and m/z 182
were present, which indicated the formation of disul-
fide structure.
Scheme 1.
S
S
MeOC(O)Cl
pyridine
NH2
SH
S
NH2
SH
S
HN
OMe
NH2
NH
O
O
MeO
O
N
H
OMe
I, 79%
1375

VELIKORODOV et al.
1376
Presumably, disulfide I is formed as a result of
with sulfur, carbon(II) oxide, and water in the presence
of vases [3]; cyclization of carbamothioates with sub-
sequent cleavage of 2-alkoxybenzothiazoles thus
formed [12]; oxidation of 2-sulfanyl- or 2-alkylsul-
fanylbenzothiazoles to the corresponding sulfones and
hydrolysis of the latter; reaction of o-chloronitroben-
zenes with 2-sulfanylacetic acid followed by cyclocon-
densation of 2-(o-nitrophenylsulfanyl)acetic acid with
acetic anhydride and deacylation [3]; reaction of
1,3-benzothiazol-2-amines with alkali metal hydrox-
ides in anhydrous medium and subsequent cyclization
of o-sulfanylphenylureas [3, 13]; and reaction of 2-sul-
fanylbenzoic acid with ammonium azide and 3 equiv
of the DMF–POCl3 complex [14]. Various 2- and
3-substituted 1,3-benzothiazol-2(3H)-one derivatives
exhibit a broad spectrum of biological activity, in par-
ticular herbicidal, antimicrobial, analgesic, antioxidant,
anticonvulsant, antifungal, etc. [3, 14–16]. These com-
pounds are also important as precursors of new func-
tionally substituted derivatives [17]. In view of the
above stated, synthesis of new derivatives of 1,3-ben-
zothiazol-2(3H)-one and their subsequent biological
screening attract strong interest.
initial oxidation of 2-aminobenzenethiol into the corre-
sponding disulfide with atmospheric oxygen and sub-
sequent acylation with methyl chloroformate at the
nitrogen atoms. The formation of disulfide from
2-aminobenzenethiol in pyridine was confirmed by
special experiment. Furthermore, compound I can be
formed, at least in part, by oxidation of methyl 2-sul-
fanylphenylcarbamate. The ability of benzenethiols to
undergo oxidation by the action of atmospheric oxygen
in alkaline medium is well known [9].
The synthesis of ethyl 2-sulfanylphenylcarbamate
via reduction of the corresponding disulfide with Zn–
HCl in methanol was described in [10]. With a view to
obtain methyl 2-sulfanylphenylcarbamate we studied
reduction of disulfide I with zinc dust in glacial acetic
acid. However, instead of expected thiol we isolated
1,3-benzothiazol-2(3H)-one (II) which exists as two
tautomers [3] (Scheme 2).
Scheme 2.
S
Zn, AcOH, Δ
I
OH
N
The alkylation of 1,3-benzothiazol-2(3H)-one (II)
with 1,2-dibromoethane and allyl bromide in acetone
in the presence of potassium carbonate occurred at
the nitrogen atom and resulted in the formation of
3,3′-(ethane-1,2-diyl)bis[1,3-benzothiazol-3(2H)-one]
(III) and 3-allyl-1,3-benzothiazol-2(3H)-one (IV), re-
spectively (Scheme 4).
II, 94%
S
O
N
H
1
The structure of II was confirmed by its IR, H
NMR, and mass spectra, as well as by further chemical
transformations. Compound II is likely to be formed
via cyclization of the primary reduction product,
methyl 2-sulfanylphenylcarbamate, and subsequent
elimination of alkoxy group by the action of zinc(II)
acetate as Lewis acid (Scheme 3).
3-Allyl-1,3-benzothiazol-2(3H)-one (IV) may be
regarded as dipolarophile; it was modified by cyclo-
addition of pyridine-2-carbonitrile oxide generated in
situ from N-hydroxypyridine-2-carboximidoyl chloride
hydrochloride [18] in diethyl ether by the action of tri-
ethylamine. The reaction was regioselective, and the
product was 3-[3-(pyridin-2-yl)-4,5-dihydro-1,2-oxa-
zol-5-ylmethyl]-1,3-benzothiazol-2(3H)-one (V)
(Scheme 5). The structure of compound V was
Scheme 3.
NHCOOMe
Zn, AcOH, Δ
I
1
confirmed by the H NMR and IR spectra. Apart from
SH
1
other signals, the H NMR spectrum of V contained
two doublets of doublets typical of protons on C4 in
3,5-disubstituted isoxazole derivatives [19]. By acyla-
tion of 1,3-benzothiazol-2(3H)-one (II) with chloro-
acetyl chloride in boiling benzene (reaction time 10 h)
we obtained 3-(2-chloroacetyl)-1,3-benzothiazol-
2(3H)-one (VI) (Scheme 6). Our results are consistent
with published data [3, 20–22], according to which
1,3-benzothiazol-2(3H)-one (II) undergoes alkylation
and acylation at the nitrogen atom.
S
OMe
OH
II
–MeOH
N
H
Several procedures for the preparation of 1,3-ben-
zothiazol-2(3H)-ones have been reported. These
include cyclization of 2-aminobenzenethiols by the
action of phosgene, chloroformates, and urea [3, 11];
reductive carbonylation of substituted nitrobenzenes
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

SYNTHESIS OF 1,3-BENZOTHIAZOL-2(3H)-ONE AND SOME ITS DERIVATIVES
1377
Scheme 4.
O
S
BrCH2CH2Br
N
N
S
O
S
K2CO3, Me2CO, Δ
III, 88%
O
N
H
O
S
II
BrCH2CH=CH2
N
CH2
IV, 75%
Scheme 5.
O
N
O
N
S
CH2Cl2–Et2O
N
IV
+
C
N
N
O
V, 85%
Scheme 6.
O
S
Cl
O
N
PhH, Δ
Cl
II
+
Cl
O
VI, 79%
EXPERIMENTAL
aqueous solution of sodium chloride (100 ml) and
water (2×50 ml), dried over magnesium sulfate, and
evaporated under reduced pressure, the residue was
treated with 50 ml of diethyl ether and kept for 24 h in
a refrigerator, and the precipitate was filtered off and
recrystallized from methanol. Yield 28.8 g (79%),
colorless crystals, mp 105–108°C; published data [7]:
mp 108–112°C. IR spectrum, ν, cm–1: 3380 (NH),
2836–3108 (CH), 1740 (C=O), 1620, 1580 (C=C,
1
The H NMR spectra were measured on a Varian
VXR-500 spectrometer (500.13 MHz) from solutions
in DMSO-d6 using tetramethylsilane as internal refer-
ence. The IR spectra (4000–400 cm–1) were recorded
in KBr on a Specord M82 spectrometer. The mass
spectra (electron impact, 70 eV) were obtained on
a Finnigan MAT INCOS 50 instrument. The purity of
the isolated compounds was checked by TLC on
Silufol UV-254 plates.
1
C=Carom). H NMR spectrum (DMSO-d6), δ, ppm:
3.68 s (6H, OMe), 7.21 t (2H, Harom, J = 8.0 Hz), 7.29 t
(2H, Harom, J = 8.0 Hz), 7.33 d (2H, Harom, J = 8.0 Hz),
7.54 d (2H, Harom, J = 8.0 Hz), 9.15 br.s (2H, NH).
Mass spectrum, m/z (Irel, %): 364 (55) [M]+, 332 (11),
306 (4), 182 (57), 166 (2), 150 (100), 136 (2.5), 124
(22), 106 (6), 96 (18), 77 (7). Found, %: C 52.57;
H 4.38; N 7.39. C16H16N2O4S2. Calculated, %:
C 52.75; H 4.40; N 7.69.
Dimethyl 2,2′-disulfanediylbis(2,1-phenylene)di-
carbamate (I). Methyl chloroformate, 7.7 ml
(0.1 mol), was added dropwise under stirring to a solu-
tion of 10.7 ml (0.1 mol) of 2-aminobenzenethiol in
46 ml of anhydrous pyridine with protection from
atmospheric moisture on cooling with ice. The mixture
was stirred for 0.5 h on cooling, left to stand for 13 h at
room temperature, poured onto ice, carefully acidified
with concentrated hydrochloric acid (according to
Congo Red), and extracted with ethyl acetate (4×
25 ml). The organic phase was washed with a saturated
1,3-Benzothiazol-2(3H)-one (II). A mixture of 4 g
(0.011 mol) of disulfide I, 10 g (0.16 mol) of zinc dust,
and 10 ml of glacial acetic acid was heated for 7 h
under reflux with stirring, 2 ml of concentrated hydro-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

VELIKORODOV et al.
1378
chloric acid was added, the mixture was heated for
0.5 h more and filtered, and the filtrate was poured into
100 ml of water. The precipitate was filtered off,
washed on a filter with dilute (1:1) hydrochloric acid
(50 ml) and water (100 ml), dried in air, and recrystal-
lized from ethanol. Yield 1.56 g (94%), colorless crys-
tals, mp 138–140°C [14].
H 4.16; N 13.55. C16H13N3O2S. Calculated, %:
C 61.74; H 4.18; N 13.51.
3-(2-Chloroacetyl)-1,3-benzothiazol-2(3H)-one
(VI). A mixture of 1.51 g (10 mmol) of compound II,
0.8 ml (10.5 mmol) of chloroacetyl chloride, and 5 ml
of anhydrous benzene was heated for 10 h under
reflux. The product was washed with a 2% aqueous so-
lution of sodium hydroxide and extracted with benzene
(2×15 ml), and the extracts were combined, washed
with water, and dried over anhydrous calcium chloride.
Yield 1.8 g (79%), colorless crystals, mp 111–114°C
(from chloroform). IR spectrum, ν, cm–1: 1672, 1665
(C=O), 1595, 1580, 1465 (C–Carom), 835 (C–Cl).
1H NMR spectrum (DMSO-d6), δ, ppm: 4.25 s (2H,
3,3′-(Ethane-1,2-diyl)bis[1,3-benzothiazol-3(2H)-
one] (III). A mixture of 1.51 g (10 mmol) of 1,3-ben-
zothiazol-2(3H)-one (II), 0.43 ml (5 mmol) of freshly
distilled 1,2-dibromoethane, and 1.38 g (10 mmol) of
anhydrous potassium carbonate in 7 ml of acetone was
heated for 6 h at 70°C. The mixture was cooled,
diluted with water (25 ml), and extracted with diethyl
ether (3×25 ml). The extract was washed with a 10%
aqueous solution of sodium hydroxide (100 ml) and
water (50 ml) and dried over potassium carbonate.
The solvent was removed, and the residue crystallized.
Recrystallization from methanol gave 1.44 g (88%) of
compound (III) as colorless crystals with mp 249–
251°C; published data [20]: mp 250–251°C.
CH2), 7.12.t (1H, Harom, J = 8.0 Hz), 7.37 d (1H, Harom
,
J = 8.0 Hz), 7.41 d.t (1H, Harom, J = 8.0, 35.0 Hz),
8.28 d (1H, Harom, J = 8.0 Hz). Mass spectrum, m/z (Irel,
%): 229 (15.7), 227 (48.6), 152 (30.3), 151 (100), 123
(68.6), 77 (41.4). Found, %: C 47.37; H 2.55; N 6.08.
C9H6ClNO2S. Calculated, %: C 47.47; H 2.64; N 6.15.
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3-Allyl-1,3-benzothiazol-2(3H)-one (IV) was syn-
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Yield 1.4 g (75%), yellowish oily substance, bp 162–
164°C (5 mm); published data [22]: bp 155–157°C
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