Synthesis of benzo[b]furan-2-thioles from 4-(2-Hydroxyaryl)-1,2,3- thiadiazoles

Article abstract of DOI:10.1134/S1070428012050168

4-(2-Hydroxyaryl)-1,2,3-thiadiazoles treated with bases decompose with nitrogen liberation and the formation of benzo[b]furan-2-thiolates. On acidifying the thiolates benzo[b]furan-2-thiols were obtained. 4-(4-and -5-Benzyloxy-2-hydroxyphenyl)-1,2,3-thiadiazoles formed analogously the corresponding benzo[b]furan-2-thiolates whose acidifying afforded polymeric compounds.

Full text of DOI:10.1134/S1070428012050168

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 5, pp. 728−735. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © M.L. Petrov, M. Iekhlev, F.S. Teplyakov, D.A. Androsov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 5,
pp. 728−734.
Synthesis of Benzo[b]furan-2-thioles
from 4-(2-Hydroxyaryl)-1,2,3-thiadiazoles
M. L. Petrova, M. Iekhlevb, F. S. Teplyakova, and D. A. Androsova
aSt. Petersburg State Technological Institute, St. Petersburg,190013 Russia
e-mail: mlpetrov@lti-gti.ru
bDepartment of Chemistry, Faculty of Sciences, University of Jijel, Algeria
Received December 2, 2011
Abstract—4-(2-Hydroxyaryl)-1,2,3-thiadiazoles treated with bases decompose with nitrogen liberation and the
formation of benzo[b]furan-2-thiolates. On acidifying the thiolates benzo[b]furan-2-thiols were obtained. 4-(4-
and -5-Benzyloxy-2-hydroxyphenyl)-1,2,3-thiadiazoles formed analogously the corresponding benzo[b]furan-2-
thiolates whose acidifying afforded polymeric compounds.
DOI: 10.1134/S1070428012050168
Among the derivatives of benzo[b]furan-2-thiols only
R
R
the unsubstituted benzo[b]furan-2-thiol, 3-allylbenzofu-
ran-2-thiol, and several 2-sulfanylbenzo[b]furan-3-alde-
hydes [1–8] have been known up till now. The benzo[b]
furan-2-thiol was prepared by metallation of benzo[b]
furan with butyllithium followed by the treatment with
sulfur and acidifying to obtain benzo-[b]furan-2-thiol
[1, 4]. 2-Sulfanylbenzo[b]furan-3-aldehydes were syn-
thesized from 2-halobenzo[b]furan-3-aldehydes under
the action of sodium hydrogen sulfite [6, 7]. 3-Allylben-
zofuran-2-thiol was obtained by the rearrangement of
allyl 2-benzofuryl sulfide [8]. The benzo[b]furan-2-thiol
derivatives exhibit a biological action [1] and are used
in the organic synthesis [1–7].
NH2NHCO2Et
O
NNHCO2Et
OH CH3
OH CH3
IIа_IIf
Iа_If
R
SOCl2
N
N
S
OH
IIIа_IIIf
R = H (a), 4-Me (b), 5-Me (c), 5-Cl (d), 4-BnO (e).
5-BnO (f).
We have developed a new method for the preparation
of both unsubstituted and substituted in the aromatic ring
benzo[b]furan-2-thiols from available 4-(2-hydroxyaryl)-
1,2,3-thiadiazoles IIIa–IIIh. 1,2,3-Thiadiazoles IIIa–
IIIc were obtained from 2-hydroxyacetophenones Ia–Ic
through the formation of the corresponding ethoxycar-
bonylhydrazones IIa–IIc with subsequent treatment with
thionyl chloride [9]. 1,2,3-Thiadiazoles IIId–IIIf were
obtained similarly.
4-(2-Hydroxyaryl)-1,2,3-thiadiazoles IIIa–IIIh under
the action of a base (potassium carbonate) in anhydrous
DMF (thiadiazole IIIh at treatment with potassium tert-
butylate in anhydrous THF) decomposed with nitrogen
evolution and the formation of potassium 2-(2-hydroxya-
ryl)ethynethiolate IVa–IVh. Further the intramolecular
proton transfer provided thioketene derivatives Va–Vh.
As a result of the intramolecular cyclization involving
the hydroxy group and the thioketene fragment followed
by acidifying of anions VIa–VId, VIg, VIh we obtained
benzo[b]furan-2-thiols VIIa–VIIf.
4-(2-Hydroxy-3-iodo-5-chlorophenyl)-1,2,3-thiadia-
zole (IIIg) and 4-(2-hydroxy-3-nitro-5-chlorophenyl)-
1,2,3-thiadiazole (IIIh) were prepared by iodination and
nitration respectively of 4-(2-hydroxy-5-chlorophenyl)-
1,2,3-thiadiazole (IIId).
The structure of compounds VIIa–VIIf was proved
by 1H, 13C NMR and mass spectra by the coincidence of
the constants with the published data and by reactions of
728

SYNTHESIS OF BENZO[b]FURAN-2-THIOLES
729
S_
R
R
R
K2CO3
Δ, DMF, _N2
S_
IIIа_IIIh
C
S
O_
O
VIа_VIh
H+
OH
IVа_IVh
Vа_Vh
Здесь все пра-
вильно?
Здесь все пра-
вильно?
R
R
S
SH
O
O
VIIа_VIIf
IV, V, R = H (a), 4-Me (b), 5-Me (c), 5-Cl (d), 4BnO (e), 5BnO (f), 5-Cl, 3-I (g), 5-Cl, 3-NO2 (h); VI, R = H (a), 6-Me
(b), 5-Me (c), 5-Cl (d), 6-BnO (e), 5-BnO (f), 5-Cl, 7-I (g), 5-Cl, 7-NO2 (h); VII, R = H (a), 6-Me (b), 5-Me (c), 5-Cl (d),
5-Cl, 7-I (e), 5-Cl, 7-NO2 (f).
alkylation and acylation.
VIId–VIIf with electron-withdrawing substituents the
thiol tautomer prevails.
1H NMR spectra of thiols VIIa–VIIf registered in
CDCl3 solution at room temperature show that under these
conditions compounds VIIa–VIIf exist as s mixture of
tautomers. The proton at the sulfur atom of the enthiol
tautomer gives rise to a singlet in the region 3.69–4.02
ppm with the intensity equal to that of the H3 proton
of the benzofuran ring (s, 6.70–6.85 ppm), two protons
of the CH2 group of the benzofuran ring of the thione
form appear as a singlet in the region 4.19–4.40 ppm
The protons of the benzene rings of benzo[b]-furan-2-
thiols VIIa–VIIf are observed as complex multiplets in
the region 7.0–8.0 ppm, the protons of the methyl group
of benzo[b]furan-2-thiols VIIb, VIIc are seen as two
singlets at 2.2–2.5 ppm. Thus it is possible to estimate
the quantitative ratio of enthiol and thione tautomers
of benzofurans VIIa–VIIf under the conditionsof the
measurement (see the table). In benzo[b]furan-2-thiols
According to published data in benzene solution of
benzo[b]furan-2-thiol (VIIa) the ratio enthiol and thione
forms equaled 1:1 [2].
In the 13C NMR spectra of benzo[b]furan-2-thiols
VIIa–VIIf the signals of 13C nuclei of enthiol and thi-
one tautomers are well distinguished. The methylene
group CH2 of the thione tautomer appears in the region
48.6–48.13 ppm, the thiocarbonyl group C=S, in the re-
gion 215.8–216.73 ppm. The characteristic peaks of the
13C nuclei of the enthiol form are observed in the region
110.7–111.3 (C3) and 150.5–155.79 (C2) ppm.
In the mass spectra of benzo[b]furan-2-thiols VIIa–
VIIf the peaks of the molecular ions were detected whose
isotope composition was in agreement with calculations.
Further fragmentation of the molecular ions is similar
to that of the fragment ions of 2-alkylsulfanylbenzo[b]-
furans [8] and is consistent with the structure of benzo[b]-
furan-2-thiols VIIa–VIIf.
1H NMR spectra of benzofuran-2-thiols VIIa–VIIf
Notwithstanding the tautomerism of compounds
VIIa–VIIf their alkylation and acylation occurred ex-
clusively at the S atom. For instance, the alkylation of
5-methyl- and 5-chlorobenzofuran-2-thiols VIIc, VIId
with N-(4-methoxyphenyl)chloroacetamide in the pres-
ence of potassium hydroxide in methanol furnished the
corresponding alkylsulfanylbenzo[b]furans VIIIa, VIIIb
in 92 and 56% yield respectively. The heating of thiol
VIId in acetic anhydride in the presence of a catalytic
quantity of phosphoric acid provided S-acetyl derivative
IX in 78% yield.
δ, ppm (CDCl3)
Tautomers
ratio
thiol–thione
Compound
no.
CH2
(thione)
SH
H3 (thiol)
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
3.70
3.66
3.68
3.76
3.85
4.02
4.23
6.79
6.74
6.69
6.70
6.81
6.85
1.04 : 1
0.68 : 1
0.61 : 1
2.13 : 1
6.25 : 1
16.7 : 1
4.18
4.16
4.19
4.32
4.40
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

PETROV et al.
OMe
730
O
HN
O
OMe
Cl
HN
R
S
KOH_methanol, Δ
O
O
R
VIIIа, VIIIb
SH
VIIв, VIId
O
O
Cl
Me
S
Ac2O, H3PO4
Δ
IX
1,2,3-Thiadiazoles IIIe, IIIf with donor substituents
also decomposed with nitrogen liberation under the action
of a base (potassium carbonate) in anhydrous DMF to
give anions of benzo[b]furan-2-thiols VIe, VIf. However
the subsequent acidifying of anions VIe, VIf led to the
formation of only polymeric products. The structure of
these thiolates VIe, VIf is confirmed by the alkylation
with benzyl chloride to obtain 2-benzylsulfanyl-6- and
5-benzyloxybenzo[b]-furans Xa, Xb.
solvents used in the study were purified and dried by
standard procedures. 2-Hydroxy-5-chloroacetophenone
(Id) was obtained by reacting p-chlorophenyl acetate with
aluminum chloride by procedure [10]. 4- and 5-Benzy-
loxy-2-hydroxyacetophenones Ie, If were obtained by the
reaction of 2,4- and 2,5-dihydroxyacetophenones with
benzyl chloride as described in [11, 12].
2-Hydroxy-5-chloroacetophenone ethoxycarbon-
ylhydrazone (IId). A solution of 17 g (100 mmol) of
compound Id, 11.45 g (110 mmol) of ethoxycarbon-
ylhydrazine and 2–3 drops of acetic acid in 50 ml of
2-propanol was boiled for 2–3 h and left overnight.
The separated precipitate was filtered off, washed with
2-propanol, and dried in air. Yield 23.69 g (92%). Col-
orless needle crystals, mp 185°C (2-propanol), Rf 0.49
R
BnCl
VIe, VIf
SBn
O
Xа, Xb
R = 6-BnO (а), 5-BnO (b).
1
(chloroform). H NMR spectrum (DMSO-d6), δ, ppm:
1.32 t (3H, CH2CH3, J 7.1 Hz), 2.28 s (3H, CH3C=N),
4.23 q (2H, CH2CH3, J 7 Hz), 6.83 d (1H, H3Ph, J 8 Hz),
7.18 d.d (1H, H4Ph, Jo 7.9 , Jm 2.1 Hz), 7.44 d (1H,
H6Ph, J 8 Hz), 10.74 br.s (1H, NH), 12.84 br.s (1H,
OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 13.19
(CH2CH3), 14.43 (CH3C=N), 61.06 (CH2CH3), 118.67
(C3), 120.88 (C1), 122.06 (C5), 126.92 (C6), 129.77 (C4),
150.96 (C=N), 153.79 (C=O), 157.05 (C2). Mass spec-
trum, m/z (Irel, %): 256 (100) [M]+, 239 (79) [M –OH]+,
210 (49) [M – EtOH]+, 208 (42) [M – EtOCO]+, 167 (83)
[M – EtOCONH2]+, 154 (77), 148 (51), 125 (53), 91 (98).
Found, %: C 51.16, 51.39; H 5.08, 5.32. C11H13ClN2O3.
Calculated, %: C 51.47; H 5.1. M 256.69.
The structure of alkylsulfanylbenzo[b]furans VIIIa,
VIIIb and benzylsulfanylbenzo[b]furans Xa, Xb was
proved by NMR and mass spectra. In the 1H NMR spectra
of these compounds recorded in DMSO-d6 the character-
istic signals of the H3 of the heterocycle appeared in the
region 6.6–6.9 ppm, same as in the spectra of benzo[b]-
furan-2-thiols VIIa–VIIf.
EXPERIMENTAL
Melting points were measured on a Boёtius heat-
ing block. 1H and 13C NMR spectra were registered on
a spectrometer BrukerAMX-400 (400 and 100 MHz), as
internal reference served the signals of residual protons
and of carbon nuclei of deuterated solvents. Mass spectra
were taken on an instrument Finnigan INCOS MAT 95
with a direct admission of the sample into the ion source,
the energy of ionizing electrons 70 eV, the temperature
of ionizing chamber 200°C. The reactions progress was
monitored by TLC on Silica Gel 60 F254 plates, devel-
opment under UV irradiation and in iodine vapor. All
Compounds IIe, IIf were similarly obtained.
4-Benzyloxy-2-hydroxyacetophenone ethoxycar-
bonylhydrazone (IIe) was obtained from 1 g (4,1 mmol)
of compound Ie, 0.82 g (7.9 mmol) of ethoxycarbonyl-
hydrazine, 20 ml of 2-propanol, and several drops of hy-
drochloric acid. Yield 1.3 g (96%). Colorless crystals, mp
1
177–178°C, Rf 0.3(ethyl acetate– hexane, 1 : 2). H NMR
spectrum (DMSO-d6), δ, ppm: 1.32 t (3H, CH3CH2,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

SYNTHESIS OF BENZO[b]FURAN-2-THIOLES
731
OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 117.94
(C3), 118.88 (C1), 123.14 (C5), 128.29 (C6), 129.31 (C4),
134.81(C4Ht), 153.49(C5Ht), 157.0(C2). Mass spectrum,
m/z (Irel, %): 212 (62) [M]+, 184 (64) [M – N2]+, 155 (81),
149 (55), 121 (100), 89 (93). Found, %: C 45.07, 45.29;
H 2.42, 2.51. C8H5ClN2OS. Calculated, %: C 45.19;
H 2.37. M 212.65.
J 7.7 Hz), 2.23 s (3H, CH3C=N), 4.19 q (2H, CH2CH3,
J 7.8 Hz), 5.08 s (2H, CH2Ph), 6.41 d (H3Ph, J 2.4 Hz),
6.45 d.d (H5Ph, Jo 8.7, Jm 2.4 Hz ), 7.31 d (H6Ph, J 8.7 Hz),
7.33-7.47 m (5H, Ph), 10.49 s (1H, NH), 13.03 s (1H,
OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 13.50
(CH2CH3), 14.60 (CH3C=N), 61.16 (CH2CH3), 69.29
(CH2Ph), 102.61 (C3), 106.23 (C5), 113.14 (C1), 127.76
(C2, C6Bn), 127.96 (C4Bn), 128.56 (C3, C5Bn), 129.28 (C6),
137.01 (C1Bn), 153.67 (C=O), 154.20 (C=N), 160.16 (C2),
160.41 (C4). Mass spectrum, m/z (Irel, %): 328 (5) [M]+,
240 (4), 225 (3), 91 [Bn]+ (100), 77 (4), 65 (21). Found,
%: C 65.46, 65.73; H 6.27, 6.43. C18H20N2O4. Calculated,
%: C 65.84; H 6.14. M 328.36.
4-(4-Benzyloxy-2-hydroxyphenyl)-1,2,3-thiadia-
zole (IIIe). To a solution of 2.3 g (7 mmol) of compound
IIe in 25 ml of chloroform was added 3.4 g (28 mmol)
of thionyl chloride in 35 ml of chloroform. The reaction
gradually started. After the end of vigorous gas evolu-
tion the reaction mixture was heated for 1 h at 60°C.
On cooling to 20–25°C the reaction mixture was diluted
with 200 ml of water. The organic layer was separated,
chloroform was distilled off in a vacuum, the residue
was chromatographed on a column packed with silica gel
L 40/100, eluent ethyl acetate–hexane, 1:4. Yield 1.25 g
(63%). Light-yellow crystals, mp 123–127°C, Rf 0.53
5-Benzyloxy-2-hydroxyacetophenone ethoxy-
carbonylhydrazone (IIf) was obtained from 1.5 g
(6.22 mmol) of compound If, 0.65 g (6.22 mmol) of
ethoxycarbonylhydrazine, 50 ml of ethanol, and several
drops of hydrochloric acid. Yield 1.25 g (63%). Colorless
crystals, mp 162–164°C, Rf 0.5 (ethyl acetate–hexane,
1
1:2). H NMR spectrum (DMSO-d6), δ, ppm: 1.30 t (3H,
1
(ethyl acetate–hexane, 1:2). H NMR spectrum (CDCl3),
CH3CH2, J 6.9 Hz), 2.26 s (3H, CH3C=N), 4.21 q (2H,
δ, ppm: 5.10 s (2H, CH2Ph), 6.64 d (H5Ph, J 8.1 Hz), 6.73 s
(H3Ph), 7.36–7.44 m (5H, Ph), 7.54 d (H6Ph, J 8.1 Hz),
8.63 s (H5Ht), 10.70 s (1H, OH). 13C NMR spectrum
(DMSO-d6), δ, ppm: 70.04 (CH2Ph), 103.09 (C3), 108.05
(C1), 108.40 (C5), 127.49 (C2, C6Bn), 128.11 (C6), 128.35
(C4Bn), 128.48 (C1Bn), 128.62 (C3, C5Bn), 136.46 (C4Ht),
157.57 (C5Ht), 161.32 (C2), 162.23 (C4). Mass spectrum,
m/z (Irel, %): 284 (12) [M]+, 256 (13) [M – N2]+, 199
(12), 165 (37), 91 (100) [Bn]+, 65 (8). Found, %: C
63.04, 63.27; H 4.01, 4.29. C8H5ClN2OS. Calculated, %:
C 63.36; H 4.25. M 284.33.
CH2CH3, J 6.9 Hz), 5.02 s (2H, CH2Ph), 6.74 d (H3
,
Ph
J 8.8 Hz), 6.90 d.d (H4Ph, Jo 8.9, Jm 2.9 Hz ), 7.27–7.43 m
(5H, Ph), 7.69 d (H6Ph, J 2.9 Hz), 10.64 s (1H, NH), 12.29 s
(1H, OH). 13C NMR spectrum (DMSO-d6, δ, ppm: 13.47
(CH2CH3), 14.60 (CH3C=N), 61.13 (CH2CH3), 70.21
(CH2Ph), 114.01 (C6), 117.60 (C4), 117.65 (C3), 119.76
(C1), 127.63 (C4Bn), 127.65 (C2, C6Bn), 128.35 (C3, C5Bn),
137.47 (C1Bn), 150.57 (C5), 152.62 (C=O), 152.64 (C2),
154.02 (C=N). Mass spectrum, m/z (Irel, %): 328 (4) [M]+,
237 (42) [M – Bn]+, 191 [M – Bn–EtOH]+ (10), 147 (25)
[M – Bn–EtOCONH2]+, 119 (8), 107 (11), 91 [Bn]+ (100),
79 (12), 65 (26 ). Found, %: C 66.04, 66.17; H 6.01, 6.32.
C18H20N2O4. Calculated, %: C 65.84; H 6.14. M 328.36.
Compound IIIf was obtained similarly.
4-(5-Benzyloxy-2-hydroxyphenyl)-1,2,3-thiadi-
azole (IIIf) was obtained from 1.3 g (4,57 mmol) of
compound IIf in 25 ml of chloroform, 2.2 g (18 mmol)
of thionyl chloride in 50 ml of chloroform. Yield 0.5 g
(38 %). Colorless needlecrystals, mp 117–120°C, Rf 0.52
4-(2-Hydroxy-5-chlorophenyl)-1,2,3-thiadiazole
(IIId).At 0–5°C to 18.8 g (73.3 mmol) of compound IId
was added 50 ml of thionyl chloride cooled to 0–5°C, then
the cooling bath was removed, and the reaction gradu-
ally started. After the end of vigorous gas evolution the
reaction mixture was heated for 2 h at 60°C. On cooling
to 20–25°C the excess thionyl chloride was removed in
a vacuum. The residue was quenched with 50 ml of cold
water, the separated precipitate was filtered off and dried.
Yield 13.2 g (85%). Slightly colored prismatic crystals,
mp 170–172°C (ethyl acetate), Rf 0.73 (dichloromethane).
1H NMR spectrum (DMSO-d6), δ, ppm: 7.04 d (1H, H3,
J 8.6 Hz), 7.23 d.d (1H, H4Ph, Jo 8.5, Jm 2.5 Hz), 8.26 d
(1H, H6, Jm 2.5 Hz), 9.45 s (1H, H5Ht), 10.62 s (1H,
1
(ethyl acetate–hexane, 1:2). H NMR spectrum (CDCl3),
δ, ppm: 5.06 s (2H, CH2Ph), 7.01 d.d (1H, H4Ph, Jo 8.8,
Jm 2.6 Hz), 7.06 (1H, H3Ph, Jo 8.8 Hz), 7.27 d (1H, H6
,
Ph
Jm 2.9 Hz), 7.33–7.45 m (5H, Ph), 8.75 s (H5Ht), 10.03 s
(1H, OH). 13C NMR spectrum (DMSO-d6), δ, ppm: 71.25
(CH2Ph), 104.70 (C3), 105.67 (C1), 109.69 (C4), 118.20
(C2, C6Bn), 119.28 (C3, C5Bn), 120.98 (C4Bn), 127.42 (C6),
128.53 (C1Bn), 130.22 (C4), 137.12 (C4Ht), 152.27 (C5Ht),
152.62 (C2), 161.87 (C5). Mass spectrum, m/z (Irel, %):
284 (13) [M]+, 193 (37), 109 (4), 91 (100) [Bn]+, 65 (21).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

PETROV et al.
732
Found, %: C 63.52, 63.61; H 4.33, 4.51. C8H5ClN2OS.
%: C 37.29; H 1.56. M 257.65.
Calculated, %: C 63.36; H 4.25. M 284.33.
Benzo[b]furan-2-thiol (VIIa). To 0.3 g (1.68 mmol)
of thiadiazole IIIa in 10 ml of freshly distilled DMF
was added in one portion 0.46 g (3.37 mmol) of freshly
calcined powdered potassium carbonate. The reaction
mixture was boiled for 1 h at stirring (monitoring by
TLC following the consumption of the initial compound
and by the end of nitrogen liberation). The reaction mix-
ture was cooled, and the light brown slurry was poured
into 80 ml of distilled water; concn. HCl was added till
acid reaction. The precipitated yellow-red flocks were
filtered off, washed with distilled water, dissolved in
50 ml of distilled water containing 2 equiv of KOH, and
the reaction mixture was stirred at 30°C with activated
carbon for several minutes, and filtered . To the obtained
solution concn. HCl was added again till acid reaction.
The precipitated white-yellow flocks were filtered off,
washed thoroughly with cold distilled water, and dried
in a vacuum. Yield 0.17 g (68%). Light-yellow crystals,
mp 89–91°C (95–96°C [4]), Rf 0.17 (ethyl acetate–hex-
4-(2-Hydroxy-3-iodo-5-chlorophenyl)-1,2,3-thia-
diazole (IIIg). To a solution of 1.58 g (28.24 mmol) of
potassium hydroxide in 50 ml of methanol was added at
stirring 5 g (23.53 mmol) of compound IIId. To the solu-
tion obtained was added by small portions a solution of
7.17 g (28.24 mmol) of iodine in 70 ml of 2-propanol. The
potassium iodide immediately started to precipitate.After
1 h of stirring the reaction mixture was neutralized with
acetic acid and diluted with 300 ml of cold water contain-
ing a little sodium thiosulfate. The separated precipitate
of white flocks was filtered off, washed with water, dried,
and crystallized from ethyl acetate. Yield 7.47 g (94%).
Colorless prismatic crystals, mp 215–216°C, Rf 0.44
[ethyl acetate– petroleum ether (40–70°C), 1:4]. 1H NMR
spectrum (DMSO-d6), δ, ppm: 7.74 s (1H, H4), 8.12 s
(1H, H6), 9.74 s (1H, H5Ht), 10.82 s (1H, OH). 13C NMR
spectrum (DMSO-d6), δ, ppm: 90.54 (C3), 120.04 (C1),
125.83 (C5Ht), 129.49 (C6), 137.55 (C5), 139.24 (C4),
153.87 (C4Ht), 158.44 (C2). Mass spectrum, m/z (Irel, %):
338 (16) [M+], 310 (21) [M – N2]+, 183 (31) [M – N2 – I]+,
155 (100), 119 (32). Found, %: C 28.24, 28.49; H 1.37,
1.54. C8H4ClIN2OS. Calculated, %: C 28.38; H 1.19.
M 338.55.
1
ane, 1:2). H NMR spectrum (CDCl3), δ, ppm: 3.69 s
(SH), 4.23 s (CH2), 6.79 s (H3Ht), 7.18 × 7.46 (4H, HHt.).
13C NMR spectrum (CDCl3), δ, ppm: 48.06 (CH2thione),
110.11 (C3thiol), 110.40, 110.83, 119.80, 122.56, 123.96,
124.00, 124.53, 125.18, 128.25, 128.41, 142.79 (C8thiol),
155.79 (C2thiol), 158.21 (C8thione), 216.31 (C2thione). Mass
spectrum, m/z (Irel, %): 150 (100) [M]+, 121 (50) [M – O–
CH]+, 90 (21), 77 (19), 63 (18), 51 (23), 39 (32).
4-(2-Hydroxy-3-nitro-5-chlorophenyl)-1,2,3-
thiadiazole (IIIh). To a slurry of 10 g (47.06 mmol) of
thiadiazole IIId, 150 ml of acetic acid, and 20 ml of acetic
anhydride was added dropwise at stirring 4 ml of 65%
nitric acid. Within several minutes the color of the reac-
tion mixture changed from white to yellow-green, and the
precipitate dissolved. The reaction mixture was stirred for
1 h at room temperature and then for several minutes at
50°C. The mixture was diluted with 70 ml of water and
left overnight. The separated precipitate was filtered off,
washed with water, dried, and crystallized from 2-pro-
panol. Yield 11.5 g (95%), greenish-yellow prismatic
crystals, mp 137–138°C, Rf 0.51 [ethyl acetate–petroleum
Compounds VIIb–VIIf were similarly obtained.
6-Methylbenzo[b]furan-2-thiol (VIIb) was ob-
tained from 0.4 g (2 mmol) of thiadiazole IIIb and
0.57 g (4.1 mmol) of potassium carbonate. Yield 0.18 g
(56%). Light-yellow crystals, mp 60–64°C, Rf 0.3 (ethyl
acetate–hexane, 1:2). 1H NMR spectrum (CDCl3), δ,
ppm: 2.38 s (3H, CH3thione), 2.44 s (3H, CH3thiol,), 3.66 s
(1H, SH), 4.18 s (2H, CH2thione), 6.74 s (1H, H3Ht), 6.98 ×
7.33 m (3H, HHt). 13C NMR spectrum (CDCl3), δ, ppm:
21.55 (CH3thione), 21.58 (CH3thiol), 48.32 (CH2thione),
111.04 (C3thiol), 111.58, 119.72, 122.45, 123.74, 124.39,
125.63, 126.11, 134.74, 139.29, 142.04, 156.68 (C2thiol),
158.84 (C8thiol), 165.87 (C8thione), 217.44(C2thione). Mass-
spectrum, m/z (Irel, %): 164 (54) [M]+, 163 (7) [M – H]+,
135 (29) [M – O– CH]+, 131 (13) [M – H–S]+, 91 (45),
77 (49), 63 (32), 51 (65), 39 (100). Found, %: C 65.93,
66.12; H 4.76, 4.99. C9H8OS. Calculated, %: C 65.82;
H 4.91. M 164.22.
1
ether (40–70°C), 1:4]. H NMR spectrum (DMSO-d6), δ,
ppm: 8.07 s (1H, H6), 8.59 s (1H, H4), 9.56 s (1H, H5Ht),
11.24 br.s (1H, OH). 13C NMR spectrum (DMSO-d6),
δ, ppm: 123.61 (C1), 123.93 (C5Ht), 124.72 (C4), 134.95
(C5), 137.34 (C6), 147.34 (C3), 148.88 (C4Ht), 154.83
(C2). Mass spectrum, m/z (Irel, %): 257 (47) [M+], 229
(97.5) [M –N2]+, 211 (100) [M – NO2]+, 183 (94) [M
– N2 – NO2]+, 154 (56), 119 (90), 91 (30). Found, %:
C 37.01, 37.14; H 1.75, 1.89. C8H4ClN3O3S. Calculated,
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SYNTHESIS OF BENZO[b]FURAN-2-THIOLES
733
C8H4ClIOS. Calculated, %: C 30.94; H 1.30. M 310.54.
5-Methylbenzo[b]furan-2-thiol (VIIc) was obtained
from 0.96 g (5 mmol) of thiadiazole IIIc and 1.38 g
(10 mmol) of potassium carbonate. Crystallization from
methanol. Yield 0.45 g (55%). Light-yellow needle
crystals, mp 83–85°C, Rf 0.63 (ethyl acetate–hexane,
7-Nitro-5-chlorobenzo[b]furan-2-thiol (VIIf) was
obtained from 2.5 g (9.7 mmol) of thiadiazole IIIh, but
its decomposition was carried out in THF by adding
3.26 g (29.1 mmol) of potassium tert-butylate within
1 h at 60°C. Yield 1.8 g (80%). Light-yellow powder,
mp 122–123°C, Rf 0.27 (methanol–chloroform, 1:9).
1H NMR spectrum (CDCl3), δ, ppm: 4.02 s (1H, SH),
4.40 s (2H, CH2thione), 6.85 s (1H, H3Ht), 7.76 s (1H,
H4thiol), 7.96 s (1H, H4thione), 8.07(1H, H6thiol), 8.32 (1H,
H6thione). 13C NMR spectrum (CDCl3), δ, ppm: 50.08 (CH-
2thione), 109.27 (C3thiol), 115.07, 120.67 C6thiol), 122.88,
124.40, 126.46 (C4thiol), 128.16, 129.10, 133.37, 134.19,
139.25, 146.76, 152.54, 154.12, 205.74 (C2thione). Mass
spectrum, m/z (Irel, %): 229 (100) [M]+, 228 (14) [M –
H]+, 199 (11) [M – NO]+, 183 (384) [M – NO2]+, 157
(16), 150 (315) [M – NO2 – SH]+, 119 (47). Found, %:
C 41.92, 42.14; H 1.87, 1.95. C8H4ClNO3S. Calculated,
%: C 41.84; H 1.76. M 229.64.
1
1 : 2). H NMR spectrum (CDCl3), δ, ppm: 2.33 s (3H,
CH3thione), 2.40 s (3H, CH3thiol), 3.68 s (1H, SH), 4.16 s
(2H, CH2thione), 6.69 s (1H, H3Ht), 7.06–7.24 (3H, HHt ).
13C NMR spectrum (CDCl3), δ, ppm: 20.61 (CH3thione),
20.85 (CH3thiol), 48.13 (CH2thione), 109.63 (C3thiol), 109.90,
110.73, 119.61, 124.33, 125.11, 125.21, 128.34, 128.75,
132.03, 134.36, 142.60 (C8thiol), 154.27 (C2thiol), 156.30
(C8thione), 216.73 (C2thione). Mass spectrum, m/z (Irel, %):
164 (100) [M]+, 163 (20) [M – H]+, 135 (58) [M – O –
CH]+, 131 (21) [M – H – S]+, 121 (10), 103 (19), 91 (39),
78 (18), 63 (17), 51 (25), 39 (29). Found, %: C 65.54,
65.77; H 5.21, 5.33. C9H8OS. Calculated, %: C 65.82;
H 4.91. M 164.22.
5-Chlorobenzo[b]furan-2-thiol (VIId) was ob-
tained from 6 g (28.23 mmol) of thiadiazole IIId, 7.8 g
(56.5 mmol) of potassium carbonate, and 50 ml of DMF.
Yield 4.5 g (86%). Light-yellow crystals, mp 89–90°C,
2-(5-Methylbenzo[b]furan-2-ylsulfanyl)-N1-(4-
methoxyphenyl)acetamide (VIIIa). To a solution
of 0.55 g (9.8 mmol)of potassium hydroxide in
30 ml of 2-propanol was added 0.1 g (0.76 mmol) of
compound VIIc and 0.15 g (0.76 mmol) of N1-4-
methoxyphenylchloroacetamide. The reaction mixture
was stirred for 2 h at reflux, then it was poured into
50 ml of hot water. At cooling from the yellow solution
a white solid precipitated which was filtered off, washed
with aqueous 2-propanol, and dried. Yield 0.14 g (56%).
Colorless needle crystals, mp 144–147°C, Rf 0.47 (ethyl
acetate–hexane, 1:2). 1H NMR spectrum (CDCl3), δ,
ppm: 2.41 s (3H, CH3), 3.72 s (2H, CH2), 3.78 s (3H,
CH3), 6.84 s (1H, H3Ht), 6.86 s (2H, H3, H5Ph), 7.10 s
(1H, H6arom), 7.28 m (2H, H4, H7arom), 7.41 (2H, H2,H6Ph),
8.47 br.s (1H, NH). 13C NMR spectrum (CDCl3), δ,
ppm: 21.04 (CH3), 38.93 (CH2), 55.31 (OCH3), 110.38
(C3Ht), 111.68 (C7Ht), 114.08 (C3, C5Ph), 120.41 (C4Ht),
121.73 (C2, C6Ph), 126.24 (C6Ht), 128.14 (C9Ht), 130.46
(C5Ht), 132.65 (C1Ph), 147.71 (C8Ht), 154.75 (C4Ph),
156.68 (C2Ht), 165.28 (C=O). Mass spectrum , m/z
(Irel, %): 327 (52) [M]+, 253 (5), 179 (4), 163 (45) [M –
CH2CONHC6H4OCH3]+, 147 (4), 136 (30), 123 (100),
108 (42), 91 (31), 77 (12). Found, %: C 66.13, 66.29; H
5.41, 5.49. C18H17NO3S. Calculated, %: C 66.04; H 5.23.
M 327.39.
1
Rf 0.40 (methanol–chloroform, 1:9). H NMR spectrum
(CDCl3), δ, ppm: 3.76 s (1H, SH), 4.19 s (2H, CH2thione),
6.70 s (1H, H3Ht), 7.05–7.45 m(3H, HHt). 13C NMR spec-
trum (CDCl3), d, ppm: 48.62 (CH2thione), 110.73 (C3thiol),
111.90, 112.17, 120.20, 124.91, 127.73, 129.06, 129.35,
130.38, 130.94, 145.79 (C8thiol), 154.90 (C2thiol), 157.44
(C8thione), 215.8 (C2thione). Mass spectrum , m/z (Irel, %):
184 (95) [M]+, 155 (97), 149 (48) [M – Cl]+, 121 (100),
112 (12), 105 (24), 93 (32), 77 (37). Found, %: C 52.17,
52.35; H 2.81, 3.05. C8H5ClOS. Calculated, %: C 52.04;
H 2.73. M 184.64.
7-Iodo-5-chlorobenzo[b]furan-2-thiol (VIIe) was
obtained from 2 g (5.9 mmol) of thiadiazole IIIg, 1.6 g
(11.8 mmol) of potassium carbonate, and 30 ml of DMF.
Yield 1.65 g (90%). Colorless crystals, mp 118–119°C,
1
Rf 0.38 (methanol–chloroform, 1:9). H NMR spectrum
(CDCl3), δ, ppm: 3.85 s (1H, SH), 4.32 s (2H, CH2thione),
6.81 s (1H, H3Ht), 7.21 (1H, H4thione), 7.27 (1H, H6thione),
7.41(1H, H4thiol), 7.59 (1H, H6thiol). 13C NMR spectrum
(CDCl3), δ, ppm: 43.97 (CH2thione), 74.58 (C7thiol), 80.47
(C7thione), 111.28 (C3thiol), 116.47, 120.18, 124.60, 129.72,
132.96, 135.47, 137.67, 142.21, 147.02, 155.59, 161.35,
208.35 (C2thione). Mass spectrum , m/z (Irel, %): 310 (100)
[M]+, 309 [M – H]+, 183 (12) [M – I]+, 155 (437), 127
(35), 119 (23). Found, %: C 31.06, 31.21; H 1.51, 1.63.
N1-(4-Methoxyphenyl)-2-(5-chlorobenzo[b]furan-
2-ylsulfanyl)acetamide (VIIIb) was obtained analo-
gously from 0.55 g (9.8 mmol) of potassium hydroxide in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 5 2012

PETROV et al.
734
several times washed with water to remove the residual
DMF, and then it was passed through a bed of calcined
sodium sulfate. The solvent was removed in a vacuum
on a rotary evaporator, and the dark yellow oily residue
was subjected to column chromatography on a column
(3 × 20 cm) packed with silica gel of the grade L 40/100,
eluent ethyl acetate–hexane, 1 : 8. Yield 0.18 g (30%).
Yellow crystals, mp 55–60°C, Rf 0.46 (ethyl acetate–hex-
ane, 1:8). 1H NMR spectrum (CDCl3), δ, ppm: 4.18 s
(2H, SCH2Ph), 5.20 s (2H, OCH2Ph), 6.61 s (H3Ht), 7.14 s
30 ml 2-propanola, 1.5 g (8.13 mmol) of compound VIId,
and 1.62 g (8.13 mmol) of N1-(4-methoxyphenyl)-2-chlo-
roacetamide. The product wwas purified by boiling in di-
chloromethane with charcoal, then by crystallization from
2-propanole. Yield 2.1 g 74 %). Colorless fine prismatic
crystals, mp 158–159°C, Rf 0.59 (ethyl acetate–hexane,
1:1). 1H NMR spectrum (DMSO-d6), δ, ppm: 3.74 s
(3H, OCH3), 3.80 s (2H, SCH2), 6.78 s (2H, H3, H5Ph),
6.90 s (1H, H3Ht), 7.20 m (1H, H6Ht), 7.43 m (1H, H7Ht),
7.51 s (1H, H4Ht), 9.92 s (1H, NH). 13C NMR spectrum
(DMSO-d6), δ, ppm: 38.8 (SCH2), 56.01 (OCH3), 110.17
(C3Ht), 113.14 (C7Ht), 114.76 (C3, C5Ph), 120.82 (C4Ht),
121.65 (C2, C6Ph), 125.19 (C6Ht), 128.45 (C5Ht), 130.74
(C9Ht), 132.67 (C1Ph), 152.84 (C8Ht), 154.79 (C4Ph), 156.31
(C2Ht), 166.18 (C=O). Mass spectrum, m/z (Irel, %): 347
(40) [M]+, 183 (38) [2-sulfanyl-5-chlorobenzofuran]+,
164 (14) [M – 2-sulfanyl-5-chlorobenzofuran]+, 155(32),
136 (64), 123 (100), 108 (60). Found, %: C 58.54, 58.79;
H 3.78, 3.93. C17H14ClNO3S. Calculated, %: C 58.71;
H 4.06. M 347.81.
(H7 ), 7.26–7.60 m (12H, Ph, H4Ph, H5Ph). 13C NMR
Ph
spectrum (CDCl3), δ, ppm: 39.72 (CH2S), 71.27 (CH2O),
97.41 (C7Ht), 111.70 (C3Ht), 119.56 (C9Ht), 121.07 (C5Ht),
122.31 (C4Ht), 127.16 (C3, C5BnO), 127.42 (C3, C5BnS),
128.03 (C4BnO), 128.59 (C2, C6BnO, C4BnS), 128.82 (C2,
C6BnS), 136.34 (C1BnO), 137.13 (C1BnS), 149.71 (C8Ht),
152.14 (C2Ht), 155.46 (C6Ht). Mass spectrum, m/z (Irel,
%): 346 (8) [M]+, 255 (6) [M – Bn]+, 165 (7) [M –CHPh –
Bn]+, 91 (100) [ Bn]+, 65 (15). Found, %: C 76.33, 76.52;
H 5.39, 5.47. C22H18O2S. Calculated, %: C 76.27; H 5.24.
M 346.44.
2-Acetylsulfanyl-5-chlorobenzo[b]furan (IX).
A mixture of 2 g (10.8 mmol) of compound VIId, 15 ml
of acetic anhydride, and 1 drop of orthophosphoric acid
was boiled for 10 min. On cooling to room temperature
100 ml of water was added. The separated precipitate
was filtered off, washed with water, and dried. Yield
1.9 g (78%). Colorless powder, mp 83–84°C, Rf 0.65
[ethyl acetate–petroleum ether (40–70°C), 1:4]. 1H
NMR spectrum (DMSO-d6), δ, ppm: 2.45 s (3H, CH3),
6.93 s (1H, H3Ht), 7.24 m (1H, H6Ht), 7.43 m (1H, H7Ht),
7.51 s (1H, H4Ht). 13C NMR spectrum (DMSO-d6), δ,
ppm: 31.09 (CH3), 106.19 (C3Ht), 108.28 (C7Ht), 113.87
(C4Ht), 119.40 (C6Ht), 128.96 (C5Ht), 136.60 (C9Ht), 153.35
(C8Ht), 159.09 (C2Ht), 193.47 (C=O). Mass spectrum, m/z
(Irel, %): 226 (8) [M]+, 184 (62) [M – Ac]+, 155 (58), 121
(10), 111 (5), 91 (4), 43 (100) [Ac]+. Found, %: C 53.12,
53.31; H 3.27, 3.49. C17H14ClNO3S. Calculated, %: C
52.99; H 3.11. M 226.67.
5-Benzyloxy-2-benzylsulfanylbenzo[b]-furan (Xb)
was obtained similarly from 0.35 g (1.23 mmol) of thia-
diazole IIIf, 0.5 g (3.7 mmol) of potassium carbonate,
and 0.23 g (1.84 mmol) of benzyl chloride. Yield 0.31 g
(74%). Light-yellow crystals, mp 75–79, Rf 0.75 (ethyl
acetate–hexane, 1:4). 1H NMR spectrum (CDCl3), δ,
ppm: 4.14 s (2H, SCH2Ph), 5.05 s (2H, OCH2Ph), 6.59 s
(H3Ht), 7.00 s (H7Ph ), 7.24 × 7.45 m (12H, Ph, H4Ph, H6Ph).
13C NMR spectrum (CDCl3), δ, ppm: 39.22 (CH2S), 70.79
(CH2O), 104.40 (C3Ht), 111.23 (C7Ht), 111.60 (C6Ht),
113.95(C4Ht), 127.27 (C3, C5BnO, C4BnS), 127.34 (C3,
C5BnS), 127.79 (C9Ht), 128.40 (C2, C6BnS, C4BnO), 128.66
(C2, C6BnO), 128.93 (C1BnO), 137.08 (C1BnS), 150.37
(C8Ht), 151.46 (C5Ht), 155.46 (C2Ht). Mass spectrum,
m/z (Irel, %): 346 (4) [M]+, 256 (3) [M – CHPh]+, 165 (2)
[M – CHPh – Bn]+, 91 (100) [ Bn]+, 65 (87). Found, %:
C 75.98, 76.17; H 5.28, 5.52. C22H18O2S. Calculated, %:
C 76.27; H 5.24. M 346.44.
6-Benzyloxy-2-benzylsulfanylbenzo[b]furan (Xa).
A slurry of 0.5 g (1.76 mmol) of thiadiazole IIIe, 0.73 g
(5.3 mmol) of freshly calcined potassium carbonate in
15 ml of DMF was heated at 60°C пpand while vigor-
ous stirring for 30 min, then a solution was added of
0.35 g (2.64 mmol) of benzyl chloride in 3 ml of DMF.
The reaction mixture was vigorously stirred at 60°C
over 12 h, poured into 500 ml of water and extracted
with chloroform (4 × 30 ml). The organic solution was
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