4-(2-Hydroxyaryl)-1,2,3-thiadiazoles as a source of 2-benzofuranthiolates

Article abstract of DOI:10.1023/A:1022568808446

Following the Hurd-Mori procedure, 4-(2-hydroxyaryl)-1,2,3-thiadiazoles were synthesized from o-hydroxyacetophenones. Treatment of the products with bases gives 2-benzofuranthiolates which can be involved in alkylation and arylation reactions.

Full text of DOI:10.1023/A:1022568808446

Russian Journal of Organic Chemistry, Vol. 38, No. 10, 2002, pp. 1510 1518. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 10, 2002,
pp. 1563 1571.
Original Russian Text Copyright
2002 by Petrov, Dehaen, Abramov, Abramova, Androsov.
4-(2-Hydroxyaryl)-1,2,3-thiadiazoles as a Source
of 2-Benzofuranthiolates*
M. L. Petrov1, W. Dehaen2, M. A. Abramov1, I. P. Abramova1, and D. A. Androsov1
1
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 198013 Russia
e-mail: mlpetrov@tu.spb.ru
2
Department of Chemistry, University of Leuven, Celestijnelaan 200F, Leuven (Heverlee), B-3001 Belgium
Received December 24, 2001
Abstract Following the Hurd Mori procedure, 4-(2-hydroxyaryl)-1,2,3-thiadiazoles were synthesized from
o-hydroxyacetophenones. Treatment of the products with bases gives 2-benzofuranthiolates which can be
involved in alkylation and arylation reactions.
1,2,3-Thiadiazoles having no substituent in position
5 readily decompose under the action of strong bases
(e.g., potassium ethoxide or butyllithium). The reac-
tion is accompanied by evolution of nitrogen, and the
products are alkynethiolates [1, 2] (Scheme 1).
sulfides and in cycloaddition reactions. Their protona-
tion gives acetylenic thiols which are precursors of
highly reactive thioketenes [3 9] (Scheme 2). On the
other hand, 1,2,3-thiadiazoles attract interest as bio-
logically active compounds [10 12]. The first com-
mercial plant growth stimulator, Bion, was recently
synthesized on the basis of 1,2,3-benzothiadiazole-7-
carboxylic acid derivatives [13]. Dehaen et al. [14]
reported a new convenient procedure for preparation
of 2-methylthiobenzofuran by decomposition of acces-
sible 4-(2-hydroxyphenyl)-1,2,3-thiadiazole.
Scheme 1.
The present communication describes in detail the
synthesis of 4-(2-hydroxyaryl)-1,2,3-thiadiazoles and
their transformation into 2-benzofuranthiolates. While
continuing our studies in the field of synthesis and
reactivity of 5-unsubstituted 1,2,3-thiadiazoles having
The resulting acetylenic thiolates are widely used
in organic synthesis for the preparation of acetylenic
Scheme 3.
Scheme 2.
____________
*
This study was financially supported by the Russian Founda-
tion for Basic Research (project no. 00-03-32740).
I, II, III, R = R = H (a); R = OH, R = (b); R = H, R =
OH (c); R = Me, R = H (d); R = H, R = Me (e).
1070-4280/02/3810-1510$27.00 2002 MAIK Nauka/Interperiodica

4-(2-HYDROXYARYL)-1,2,3-THIADIAZOLES
1511
an active functional group (hydroxy), from o-hydroxy-
acetophenones Ia Ie we obtained the corresponding
ethoxycarbonylhydrazones IIa IIe (Scheme 3). By
the reaction of 2,5-dihydroxyacetophenone (Ic) with
p-tolylsulfonylhydrazine we synthesized tosylhydra-
zone IIc. Treatment of hydrazones IIa IIe with
thionyl chloride (Hurd Mori reaction [15]) gave new
4-(2-hydroxyaryl)-1,2,3-thiadiazoles IIIa IIIe in
an overall yield of 37 74%.
Under analogous conditions, the reaction of thiadi-
azole IIIa with a much stronger alkylating agent,
methyl iodide, gave a considerable amount of
methoxyphenylthiadiazole V (40%) together with 56%
of benzofuranyl sulfide IVa. In order to obtain sulfide
IVa in a good yield (90%), thiadiazole IIIa should be
treated with a base before addition of methyl iodide.
These data indicate intermediate formation of benzo-
furan-2-thiolates in the alkylation process.
The structure of thiadiazoles IIIa IIIe was con-
The 1H NMR spectra of 2-alkylthiobenzofurans
IVa IVe contain singlets at 6.65 6.76 ppm from
the 3-H proton. The corresponding signal of difuryl
diselenide appears as a singlet at 6.63 ppm [18].
In the 13C NMR spectra of IVa IVe, the chemical
shifts of the furan ring carbons almost coincide with
those typical of difuryl diselenide [18]. Benzofuryl
sulfides give molecular ion peaks in the mass spectra;
their isotope composition conforms to the assumed
structures. The main fragmentation pathway of the
molecular ions of IVa IVe involves cleavage of
1
firmed by the IR, H and 13C NMR, and mass spectra.
In the IR spectrum of thiadiazole IIIa, the O H
stretching vibration band is broadened and is located
1
in the region 3200 3100 cm , in keeping with
published data [16]. The 1H NMR spectra of IIIa IIIe
contain singlets from the 5-H and OH protons, which
appear in a weaker field relative to the aromatic
proton signals, e.g., for thiadiazole IIIa: 8.82 (5-H),
10.54 (OH), and 7.15 7.67 ppm (m, Harom).
In the mass spectra of thiadiazoles IIIa IIIe we
observed the corresponding molecular ion peaks,
whose isotopic composition conforms to the cal-
culated data. Further fragmentation of the molecular
ions supports their structure. The main decomposition
pathway includes elimination of nitrogen molecule;
the same process occurs under irradiation and at high
temperature [10, 17].
We made an attempt to effect alkylation of 1,2,3-
thiadiazoles IIIa IIIc in the presence of a base
(K2CO3). However, the reaction was accompanied by
decomposition of the thiadiazole ring with evolution
of nitrogen and formation of 2-benzofuranyl sulfides
IVa IVe (Scheme 4).
3
the Csp S bond, i.e., elimination of the alkyl sub-
stituent, followed by expulsion of CO molecule.
An interesting application of selective alkylation is
illustrated by Scheme 5. 4-(2,5-Dihydroxyphenyl)-
1,2,3-thiadiazole (IIIc) was treated with a base and
with 0.5 equiv of 1,11-dichloro-3,6,9-trioxaundecane.
As a result, 72% of 1,11-bis(5-hydroxy-2-benzofuryl-
thio)-3,6,9-trioxaundecane (VI) was obtained. The
latter was brought into reaction with tetraethylene
glycol bis(p-toluenesulfonate), which led to formation
of thia crown ether VII in 38% yield. Syntheses of
such crown ethers usually require preliminary protec-
tion of the phenolic hydroxy group.
The arylation of 4-(2-hydroxyaryl)-1,2,3-thiadi-
azoles IIIa, IIId, and IIIe with 2,4-dinitrochloro-
benzene in the presence of potassium carbonate fol-
lowed a pattern similar to the alkylation. The isolated
products were 2-(2,4-dinitrophenylthio)benzofurans
VIIIa VIIIc (Scheme 6). According to the TLC data,
small amounts of by-products were also formed. By
column chromatography we isolated 3-(2,4-dinitro-
phenyl)-2-(2,4-dinitrophenylthio)benzofuran (IX)
from the product mixture obtained in the reaction of
4-(2-hydroxy-4-methylphenyl)-1,2,3-thiadiazole (IIId)
with 2,4-dinitrochlorobenzene. The formation of such
a by-product suggests radical anion nature of the
colored thiadiazole decomposition products. When the
reaction was carried out under argon, no intense
coloration was observed, and the yield of by-products
was considerably lower. This assumption is also
supported by the known addition of two styrene
molecules to 2-benzofuranthiol both at the sulfur atom
and at position 3 of the benzofuran ring [19].
Scheme 4.
IV, R1 = R2 = H, R3 = Me (a); R1 = R2 = H, R3 = C16H31 (b);
R1 = R2 = H, R3 = PhCH2 (c); R1 = OH, R2 = H, R3 =
C16H31 (d); R1 = H, R2 = OH, R3 = C16H31 (e).
In all cases, the alkylating agent (benzyl bromide
or 1-bromohexadecane) was simultaneously mixed
with thiadiazole IIIa IIIc and potassium carbonate.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

1512
PETROV et al.
Scheme 5.
Scheme 6.
VIII, R1 = R2 = H (a); R1 = Me, R2 = H (b); R1 = H, R2 = Me (c).
The structure of arylation products VIIIa VIIIc
from the heteroring to give anion XII, elimination of
1
and IX was confirmed by the H and 13C NMR and
nitrogen from XII with formation of alkynethiolate
XIII (as is usually observed for 1,2,3-thiadiazoles
having no substituent in the 5-position [1, 2]), intra-
molecular proton transfer leading to thioketene XIV,
and ring closure with participation of the hydroxy
group. Intermediates X, XI, and XIII were detected
1
mass spectra. The H and 13C NMR spectral patterns
(both signal positions and their multiplicities) of the
benzofuran and 2,4-dinitrophenyl fragments in 2-(2,4-
dinitrophenylthio)benzofurans VIIIa VIIIc and IX
resemble those observed for 2-alkylthiobenzofurans
IVa IVe and 2,4-dinitrotoluene [20], respectively.
The mass spectra of VIIIa, VIIIb, and IX contain
peaks from the molecular ions whose isotope com-
position conforms to the assumed structures. The
main fragmentation pathways of compounds VIII and
IX under electron impact are illustrated by Scheme 7
for the molecular ion of 2-(2,4-dinitrophenylthio)-
benzofuran (VIIIa) as an example. In keeping with
the fragment ion peak intensities, the most probable
pathway involves formation of 4-nitro-2-nitroso-
phenylseleno and benzofuran-2-yloxy ions.
1
by H NMR spectroscopy.
Scheme 7.
1H NMR study of the mechanism of decomposition
of 4-(2-hydroxyphenyl)-1,2,3-thiadiazole (IIIa) (using
Bu4NOH as a base) showed that the reaction of IIIa
with a base gives 2-benzofuranthiolate ion (X). The
process includes several steps (Scheme 8): formation
of phenoxide ion XI, intramolecular proton transfer
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

4-(2-HYDROXYARYL)-1,2,3-THIADIAZOLES
1513
Scheme 8.
EXPERIMENTAL
with toluene) using a Dean Stark trap and was left to
stand overnight in a refrigerator. The precipitate was
filtered off and dried under reduced pressure. Yield
3.81 g (90%); mp 192 C. 1H NMR spectrum
(DMSO-d6), , ppm: 2.22 s (CH3), 2.37 s (CH3C N),
6.66 d (6-H), 6.71 d.d (4-H), 6.84 d (3-H), 7.44 d
and 7.78 d (Harom in Ts), 8.9 s (NH), 10.93 s (OH).
13C NMR spectrum (DMSO-d6), C, ppm: 14.6
(CH3C N), 21.0 (CH3), 114.0, 117.4, 118.6, 119.6,
127.4, 129.8, 135.4, 143.9, 149.3, 150.2, 158.1. Mass
spectrum, m/z (Irel, %): 320 (83) M+, 165 (90), 148
(47), 136 (100.0), 120 (23), 107 (47), 91 (80), 79 (44),
65 (65), 53 (27), 51 (22), 39 (38).
2-Hydroxy-4-methylacetophenone ethoxycar-
bonylhydrazone (IId). A solution of 5.4 g (36 mmol)
of 2-hydroxy-4-methylacetophenone (Id), 3.74 g
(36 mmol) of ethyl hydrazinecarboxylate, and 3 drops
of acetic acid in 15 ml of ethanol was heated for
30 min under reflux, cooled to 15 18 C, and left
overnight. The precipitate was filtered off and dried
under reduced pressure. Yield 7.3 g (86%); mp 159
161 C (from ethanol). 1H NMR spectrum (DMSO-d6),
, ppm: 1.24 t (CH2CH3), 2.25 s (CH3C N), 2.28 s
(CH3), 4.21 q (CH2CH3), 6.78 s (3-H), 6.69 d (5-H),
7.49 d (6-H), 10.68 s (2-OH), 12.87 s (NH). 13C NMR
spectrum (DMSO-d6), C, ppm: 12.8, 13.9, 20.3,
60.6, 116.9, 118.9, 127.3, 140.1, 153.5, 157.6, 165.0,
167.5. Mass spectrum, m/z (Irel, %): 236 (78.6) M+,
219 (35.6), 190 (85.8), 163 (31.6), 147 (82.3), 134
(100), 118 (43.9), 105 (39.5), 91 (59.2).
The melting points were determined on a Boetius
device. The IR spectra were recorded on an IKS-29
spectrometer. The 1H and 13C NMR spectra were
1
measured on Bruker Avance (300 MHz for H and
75 MHz for 13C) and Bruker AMX-400 (400 MHz for
1H and 100 MHz for 13C) instruments using solvent
signals as reference. The mass spectra (70 eV) were
run on a Kratos MS 890 high-resolution mass spec-
trometer with direct sample admission into the ion
source heated to 200 C. The progress of reactions
was monitored by TLC on Silufol UV-254 plates;
spots were visualized by UV light and iodine vapor.
All solvents were dried and purified by standard
procedures.
2,4-Dihydroxyacetophenone ethoxycarbonyl-
hydrazone (IIb). To a solution of 10 g (32.9 mmol)
of 2,4-dihydroxyacetophenone Ib in a mixture of
75 ml ethanol and 75 ml of water we added 6.84 g
(32.9 mmol) of ethyl hydrazinecarboxylate. The mix-
ture was heated for 22 h under reflux and was left
to stand overnight in a refrigerator. The precipitate
was filtered off, washed with diethyl ether (2 50 ml),
and dried under reduced pressure. Yield 9.50 g (61%),
mp 209 C (from ethanol). 1H NMR spectrum
(DMSO-d6), , ppm: 1.27 t (CH2CH3), 2.24 s
(CH3C N), 4.19 q (CH2CH3), 6.24 d (6-H), 6.30 d.d
(5-H), 9.22 s (3-H), 9.75 s (4-OH), 10.50 s (2-OH),
13.05 s (NH). 13C NMR spectrum (DMSO-d6),
,
C
ppm: 13.3, 14.5, 61.0, 103.1, 106.6, 111.7, 129.3,
154.1, 159.8, 160.1. Mass spectrum, m/z (Irel, %): 238
(100.0) M+, 237 (26), 221 (44), 192 (33), 165 (23),
150 (20), 149 (25), 136 (59), 135 (39), 107 (21).
2,5-Dihydroxyacetophenone p-tolylsulfonyl-
hydrazone (IIc). To a solution of 2 g (13.1 mmol) of
2,5-dihydroxyacetophenone (Ic) in 50 ml of toluene
we added 2.45 g (13.1 mmol) of p-tolylsulfonylhydra-
zine. The mixture was heated for 2 h under reflux
with simultaneous removal of water (as azeotrope
2-Hydroxy-5-methylacetophenone ethoxycar-
bonylhydrazone (IIe). A solution of 9.3 g (62 mmol)
of 2-hydroxy-5-methylacetophenone (Ie), 6.4 g
(62 mmol) of ethyl hydrazinecarboxylate, and 3 drops
of acetic acid in 30 ml of ethanol was heated for
30 min under reflux, cooled, and left overnight. The
precipitate was filtered off and dried under reduced
pressure. Yield 12 g (82%); mp 137 139 C (from
ethanol). 1H NMR spectrum (DMSO-d6), , ppm:
1.25 t (CH2CH3), 2.22 s (CH3C N), 2.26 s (CH3),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

1514
PETROV et al.
4.17 q (CH2CH3), 6.73 d (3-H), 7.03 d (4-H), 7.31 s
(5-H), 10.6 s (2-OH), 12.63 s (NH). 13C NMR spec-
trum (DMSO-d6), , ppm: 13.3, 14.4, 20.2, 61.1,
116.8, 119.2, 126.8, 128, 131.2, 154.1, 156, 165.7.
Mass spectrum, m/z (Irel, %): 236 (17.1) M+, 219
(9.9), 190 (47.4), 163 (7.6), 147 (100), 134 (58.7),
118 (36.6), 105 (31), 91 (31.7).
vigorous evolution of HCl ceased, the cooling bath
was removed, and the mixture was stirred for 2 h.
Excess thionyl chloride was distilled off under
reduced pressure, and the product was purified by
column chromatography on silica gel L 40/100
m
using methylene chloride ethyl acetate (10:3) as
1
eluent. Yield 0.46 g (69%); mp 216 C. H NMR
spectrum (DMSO-d6), , ppm: 6.74 d (6-H), 6.89 d.d
(4-H), 7.73 d (3-H), 9.02 s (5-OH), 9.43 s (5-H,
thiadiazole), 9.77 s (2-OH). 13C NMR spectrum
(DMSO-d6), C, ppm: 114.9, 117.26, 117.33, 134.7
(C5, thiadiazole), 147.4, 150.0, 158.4 (C4, thiadi-
azole). Mass spectrum, m/z (Irel, %): 194 (94) M+, 166
(35), 137 (100.0), 110 (37), 105 (28), 94 (27), 82 (20),
66 (31), 65 (31), 55 (21), 53 (28), 45 (26), 39 (44).
Found, %: C 49.52; H 3.15; N 14.32. C8H6N2O2.
Calculated, %: C 49.48; H 3.11; N 14.42.
4-(2-Hydroxyphenyl)-1,2,3-thiadiazole (IIIa)
[14]. A flask equipped with a reflux condenser and
a gas-outlet tube (which was connected to a system
for absorption of gaseous hydrogen chloride) was
charged with 11.8 g (50 mmol) of ethoxycarbonyl-
hydrazone IIa. It was cooled to 0 5 C, and 80 ml
of thionyl chloride cooled to 0 5 C was added. The
cooling bath was removed, and vigorous reaction
gradually started with evolution of HCl. When intense
gas evolution ceased, the mixture was heated for 1 h
at 60 C. It was then cooled to 20 25 C, and excess
thionyl chloride was distilled off under reduced pres-
sure. Cold water, 50 ml, was added to the residue,
and the precipitate was filtered off and dried to obtain
8.5 g (88%) of the crude product. Recrystallization
from water gave 6.2 g (64%) of compound IIIa as
colorless needles with mp 106 C. IR spectrum (KBr),
4-(2-Hydroxy-4-methylphenyl)-1,2,3-thiadiazole
(IIId) was synthesized as described above for com-
pound IIIa from 4.9 g (20.8 mmol) of hydrazone IId
and 20 ml of thionyl chloride. Yield 3.5 g (87%);
mp 115 117 C (from water). Rf 0.5 (eluent CHCl3).
1H NMR spectrum (DMSO-d6), , ppm: 2.37 s (CH3),
6.8 d (5-H), 6.96 s (3-H), 7.52 d (6-H), 8.72 s (5-H,
thiadiazole), 10.44 s (OH). 13C NMR spectrum
1
1
, cm : 3200 3100, 3000, 1593, 1470, 1258. H
NMR spectrum (CDCl3), , ppm: 7.00 t.d (5-H),
7.15 d.d (3-H), 7.36 t.d (4-H), 7.67 d.d (6-H), 8.82 s
(5-H, thiadiazole), 10.54 s (OH). 13C NMR spectrum
(CDCl3), , ppm: 114.5 (C1), 118.3 (C3), 120.1 (C5),
127.4 (C4), 130.0 (C6), 131.4 (C5, thiadiazole), 156.0
(C2), 162.3 (C4, thiadiazole). Mass spectrum, m/z
(Irel, %): 178 (14.5) M+, 150 (22.4) [M N2]+, 122
(37.3), 121 (100), 83 (18), 90 (55), 77 (32). Found,
%: C 54.21, 53.98; H 3.41, 3.13. C8H6N2OS. Calcu-
lated, %: C 53.93, H 3.37.
(DMSO-d6), , ppm: 21.4 (CH3), 111.9 (C1), 118.6
(C3), 121.2 (C5), 127.2 (C6), 129.1 (C5, thiadiazole),
142.0 (C4), 156 (C2), 162.4 (C4, thiadiazole). Mass
spectrum, m/z (Irel, %): 192 (52.2) M+, 164 (95.1)
[M N2]+, 135 (100), 131 (58), 103 (44.4), 91 (69.7),
77 (39.1). Found, %: C 59.27, 59.48; H 4.41, 4.18.
C9H8N2OS. Calculated, %: C 59.34, H 4.17.
4-(2-Hydroxy-5-methylphenyl)-1,2,3-thiadiazole
(IIIe) was synthesized as described above for thiadi-
azole IIIa from 11.8 g (50 mmol) of compound IIe
and 80 ml of thionyl chloride. Yield 8.5 g (88%);
mp 88 90 C (from water). Rf 0.43 (eluent CHCl3).
1H NMR spectrum (DMSO-d6), , ppm: 2.37 s (CH3),
6.82 d (3-H), 6.96 s (6-H), 7.35 d (4-H), 8.51 s (5-H,
thiadiazole), 10.69 s (OH). 13C NMR spectrum
4-(2,4-Dihydroxyphenyl)-1,2,3-thiadiazole (IIIb)
was synthesized in a similar way from 8 g
(33.61 mmol) of compound IIb and 70 ml of thionyl
chloride. The only difference was that the mixture was
heated for 3 h. The product was purified by column
chromatography on silica gel L 40/100 m using
methylene chloride ethyl acetate (10:3) as eluent.
(DMSO-d6), C, ppm: 21.3 (CH3), 112.2 (C1), 117.4
1
(C3), 124.6 (C6), 129.9 (C4), 128.4 (C5, thiadiazole),
132.6 (C5), 159.2 (C2), 159.3 (C4, thiadiazole). Mass
spectrum, m/z (Irel, %): 192 (31.3) M+, 164 (50.5)
[M N2]+, 135 (100), 131 (25), 103 (23), 91 (43.1),
77 (14.8). Found, %: C 59.19, 59.44; H 4.04, 4.35.
C9H8N2OS. Calculated, %: C 59.34, H 4.17.
Yield 4.00 g (61%), mp 209 C. H NMR spectrum
(DMSO-d6), , ppm: 6.43 d (6-H), 6.55 d (5-H),
8.08 d (3-H), 9.22 s (5-H, thiadiazole), 9.7 s (4-OH),
10.32 s (2-OH). 13C NMR spectrum (DMSO-d6),
,
C
ppm: 102.9, 107.4, 130.2, 131.9 (C5, thiadiazole),
156.0, 158.8 (C4, thiadiazole), 159.2. Found, %:
C 49.43; H 3.18; N 14.19. C8H6N2O2S. Calculated,
%: C 49.48; H 3.11; N 14.42.
2-Methylthiobenzofuran (IVa) and 4-(2-meth-
oxyphenyl)-1,2,3-thiadiazole (V). a. A suspension
of 1 g (5.62 mmol) of thiadiazole IIIa, 0.93 g
(6.74 mmol) of potassium carbonate, and 1.2 g
(8.43 mmol) of methyl iodide in 40 ml of dry acetone
4-(2,5-Dihydroxyphenyl)-1,2,3-thiadiazole (IIIc).
Thionyl chloride, 10 ml, was added at 78 C to 1.1 g
(3.44 mmol) of p-tolylsulfonylhydrazone IIc. When
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

4-(2-HYDROXYARYL)-1,2,3-THIADIAZOLES
1515
was heated for 10 h under reflux with vigorous stir-
ring. The mixture was filtered, the filtrate was
evaporated under reduced pressure, and the residue
was subjected to chromatography in a 3 30-cm
column charged with silica gel L 40/100 m using
methylene chloride cyclohexane (1:2) as eluent.
Removal of the solvent from the first fraction gave
0.52 g (56%) of benzofuran IVa as a light yellow
(11), 57 (31), 55 (27), 43 (65), 41 (44). Found, %:
C 76.77; H 10.10. C24H38OS. Calculated, %: C 76.95;
H 10.22.
2-Benzylthiobenzofuran (IVc). A suspension of
1 g (5.62 mmol) of thiadiazole IIIa, 0.93 g
(6.74 mmol) of K2CO3, and 0.85 g (6.74 mmol) of
benzyl chloride in 40 ml of dry acetone was heated
for 10 h under reflux with vigorous stirring. The
mixture was cooled and filtered, and the filtrate was
evaporated under reduced pressure. The residue was
subjected to chromatography on a 3 30-cm column
charged with silica gel L 40/100 m using methylene
chloride cyclohexane (1:2) as eluent. Yield 1.28 g
(91%), light yellow oily substance. 1H NMR spectrum
(CDCl3), , ppm: 4.14 s (SCH2), 6.65 s (3-H), 7.17
7.45 m (Harom). 13C NMR spectrum (CDCl3), C, ppm:
39.3 (CH2S), 110.9, 111.8 (C3), 120.5, 122.8, 124.8,
127.3, 128.5, 128.8, 137.1, 149.6 (C2), 156.3. Mass
spectrum, m/z (Irel, %): 240 (58) M+, 149 (11)
[M CH2Ph]+, 121 (19), 91 (100), 77 (16), 69 (25),
39 (12). Found: M+ 240.0609. C15H12OS. Calculated:
M 240.0609.
1
oily substance. H NMR spectrum (CDCl3), , ppm:
2.52 s (SCH3), 6.66 s (3-H), 7.18 t.d (5-H), 7.22 t.d
(6-H), 7.41 d (7-H), 7.46 d (4-H). 13C NMR spectrum
(CDCl3), C, ppm: 17.0 (CH3S), 107.8 (C3), 110.7
(C7), 120.1 (C4), 122.8 (C5), 123.9 (C6), 128.5 (C9),
152.2 (C2), 156.0 (C8). Mass spectrum, m/z (Irel, %):
164 (92) M+, 149 (100) [M CH3]+, 121 (50), 77 (32),
69 (10), 63 (18), 51 (17). Found: M+ 164.0298.
C9H8OS. Calculated: M 164.0296.
From the second fraction, 0.47 g (40%) of thiadi-
1
azole V was isolated. H NMR spectrum (CDCl3), ,
ppm: 3.96 s (OCH3), 7.06 d.d (3-H), 7.14 t.d (5-H),
7.41 t.d (4-H), 8.50 d.d (6-H), 9.06 s (5-H, thiadi-
azole). 13C NMR spectrum (CDCl3), C, ppm: 55.5
(CH3), 111.2, 119.6, 121.1, 130.0, 130.3, 133.3 (C5,
thiadiazole), 156.3, 158.4 (C4, thiadiazole). Mass spe-
ctrum, m/z (Irel, %): 192 (30) M+, 164 (81) [M N2]+,
149 (100) [M N2 CH3]+, 131 (50), 121 (100.0),
119 (43), 91 (40), 77 (71), 51 (41), 49 (28), 45 (29),
39 (27).
b. A suspension of thiadiazole IIIa and K2CO3 in
dry acetone was refluxed for 1 h. Methyl iodide was
then added. The only product was benzofuran IVa.
Yield 90%.
2-Hexadecylthio-6-hydroxybenzofuran (IVd).
A suspension of 0.5 g (2.58 mmol) of thiadiazole
IIIb, 0.429 g (3.09 mmol) of K2CO3, and 0.79 g
(2.58 mmol) of 1-bromohexadecane in 30 ml of dry
acetone was vigorously stirred for 10 h at 18 C. The
mixture was filtered, the filtrate was evaporated under
reduced pressure, and the residue was subjected to
chromatography on a 3 30-cm column charged with
silica gel L 40/100 m (eluent methylene chloride).
1
Yield 0.48 g (46%); colorless crystals, mp 65 C. H
NMR spectrum (CDCl3), , ppm: 0.88 t (CH3), 1.25 m
[12(CH2)], 1.39 t.d (SCH2CH2CH2), 1.63 t.d
(SCH2CH2), 2.87 t (SCH2), 4.95 m, 6.73 d (3-H),
6.76 d.d (5-H), 6.95 d (7-H), 7.32 d (4-H). 13C NMR
spectrum (CDCl3), C, ppm: 14.3, 22.7, 28.4, 29.1,
29.4, 29.5, 29.6, 29.7, 31.9, 35.2 (CH2S), 98.1, 111.7
(C3), 111.9, 120.7, 122.2, 149.2, 153.7, 157.2. Mass
spectrum, m/z (Irel, %): 390 (100) M+, 167 (12),
166 (83), 165 (21), 137 (12), 69 (11), 57 (24), 55
(23), 43 (44), 41 (30). Found, %: C 73.64; H 9.81.
C24H38O2S. Calculated, %: C 73.80; H 9.71.
2-Hexadecylthiobenzofuran (IVb). A suspension
of 0.5 g (2.81 mmol) of thiadiazole IIIa, 0.47 g
(3.37 mmol) of K2CO3, and 1.03 g (3.37 mmol) of
1-bromohexadecane in 40 ml of dry acetone was
heated for 10 h under reflux with vigorous stirring.
The mixture was cooled and filtered, and the filtrate
was evaporated under reduced pressure. The residue
was subjected to chromatography on a 3 30-cm
column charged with silica gel L 40/100 m (eluent
methylene chloride). Yield 0.97 g (92%), colorless
1
crystals, mp 30 C. H NMR spectrum (CDCl3),
,
2-Hexadecylthio-5-hydroxybenzofuran (IVe).
1-Bromohexadecane, 0.25 g (0.82 mmol), was added
at 18 C to a suspension of 0.16 g (0.82 mmol) of
thiadiazole IIIc and 0.1 g (0.90 mmol) of potassium
tert-butoxide in 10 ml of dry acetone. The mixture
was stirred at 18 C and filtered, the filtrate was
evaporated under reduced pressure, and the residue
was subjected to chromatography on a 3 20-cm
ppm: 0.88 t (CH3), 1.25 m [12(CH2)], 1.40 t.d
(SCH2CH2CH2), 1.66 t.d (SCH2CH2), 2.93 t (SCH2),
3
6.76 d (3-H, J = 0.9 Hz), 7.20 t.d (5-H), 7.25 t.d
(6-H), 7.43 m (7-H), 7.49 m (4-H). 13C NMR spec-
trum (CDCl3), C, ppm: 14.3, 22.7, 28.5, 29.1, 29.4,
29.5, 29.6, 29.7, 31.9, 34.7 (CH2S), 110.6, 110.9,
120.3, 122.8, 124.2, 128.7, 150.9 (C2), 156.2. Mass
spectrum, m/z (Irel, %): 374 (100.0) M+, 151 (13), 150
(97), 149 (19) [M C16H33]+, 121 (15), 71 (11), 69
column charged with silica gel L 40/100
(eluent
methylene chloride). Yield 0.31 g (97%); colorless
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

1516
PETROV et al.
1
crystals, mp 72 C. H NMR spectrum (CDCl3),
,
the residue was subjected to column chromatography
(3 20-cm column) on silica gel L 40/100 m using
methylene chloride ethyl acetate (10:3) as eluent.
ppm: 0.88 t (CH3), 1.25 m [12(CH2)], 1.4 t.d
(SCH2CH2CH2), 1.65 t.d (SCH2CH2), 2.92 t (SCH2),
4.69 m, 6.65 d (3-H), 6.76 d.d (6-H), 6.89 d (4-H),
7.27 d (7-H). 13C NMR spectrum (CDCl3), C, ppm:
14.3, 22.7, 28.5, 29.1, 29.3, 29.5, 29.6, 29.7, 31.9,
34.7 (CH2S), 105.2, 110.1 (C3), 111.3, 112.7, 129.5,
151.3, 151.4, 151.9 (C2). Mass spectrum, m/z (Irel, %):
390 (51) M+, 167 (13), 160 (100.0), 137 (15), 71 (12),
57 (31), 55 (28), 43 (62), 41 (46). Found, %: C 73.64;
H 9.81. C24H38O2S. Calculated, %: C 73.80; H 9.71.
1,11-Bis(5-hydroxybenzofuran-2-ylthio)-3,6,9-
trioxaundecane (VI). A mixture of 1 g (5.16 mmol)
of thiadiazole IIIc, 0.71 g (5.16 mmol) of K2CO3, and
0.16 g (0.5 equiv, 2.58 mmol) of 1,11-dichloro-3,6,9-
trioxaundecane in 40 ml of dry acetone was heated
for 12 h under reflux. The mixture was filtered, the
filtrate was evaporated under reduced pressure, and
the residue was subjected to column chromatography
(3 20-cm column) on silica gel L 40/100 m using
methylene chloride ethyl acetate (10:3) as eluent.
Yield 0.90 g (72%); colorless crystals, mp 125 C.
1H NMR spectrum (DMSO-d6), , ppm: 3.11 t
(SCH2), 3.62 t, 4.45 4.50 m, 6.75 d.d (6-H), 6.86 d
(3-H), 6.87 d (4-H), 7.31 d (7-H). 13C NMR spectrum
(DMSO-d6), C, ppm: 33.3 (CH2S), 69.1, 69.6, 69.7
(CH2O), 104.8, 109.3 (C3), 111.0, 113.0, 129.0,
1
Yield 0.3 g (38%); colorless crystals, mp 64 C. H
NMR spectrum (CDCl3), , ppm: 3.09 t (SCH2),
3.58 t, 3.65 3.75 m, 3.84 t, 4.06 t, 6.65 s (3-H),
6.83 d.d (6-H), 6.87 d (4-H), 7.23 d (7-H). 13C NMR
spectrum (CDCl3), C, ppm: 33.9 (CH2S), 68.4, 69.8,
70.0, 70.5, 70.7, 70.79, 70.84 (CH2O), 104.1, 11.1
(C3), 111.3, 113.8, 129.0, 150.6 (C2), 151.4, 155.2.
Mass spectrum, m/z (Irel, %): 648 (100.0) M+, 192
(10), 191 (21), 165 (28), 148 (11), 89 (10), 45 (50),
43 (19). Found, %: C 59.31; H 6.25. C32H40O10S2.
Calculated, %: C 59.24; H 6.21.
2-(2,4-Dinitrophenylthio)benzofuran (VIIIa).
A suspension of 0.5 g (2.8 mmol) of thiadiazole IIIa
and 0.46 g (3.4 mmol) of K2CO3 in 10 ml of dry
acetonitrile was heated for 30 min under reflux with
intense stirring. The reaction was accompanied by
vigorous evolution of nitrogen, and the mixture
turned light yellow. A solution of 0.57 g (2.8 mmol)
of 2,4-dinitrochlorobenzene in 5 ml of acetonitrile was
added dropwise, and the mixture became dark blue.
It was refluxed for 4 h and filtered, and the filtrate
was evaporated under reduced pressure. The residue
was subjected to column chromatography (3 20-cm
column) on silica gel L 40/100 m using chloroform
heptane (1:1) as eluent. Yield 0.82 g (93%); mp 145
148 C (from CHCl3 heptane). Rf 0.75 (eluent CHCl3).
1H NMR spectrum (CDCl3), , ppm: 7.14 d (4-H),
7.36 t.d (5-H), 7.38 s (3-H), 7.46 t.d (6-H), 7.55 d
(7-H), 7.7 d (6-H, dinitrophenyl), 8.22 d.d (5-H, di-
nitrophenyl), 9.13 d (3-H, dinitrophenyl). 13C NMR
spectrum (CDCl3), C, ppm: 111.9, 119.4, 121.4,
121.8, 123.9, 126.9, 127.4, 127.7, 129.5, 142.8,
144.2, 144.9, 145.2, 157.4. Mass spectrum, m/z
(Irel, %): 316 (19) M+, 183 (66) [M 2-oxobenzo-
furan]+, 133 (100) [M 2-NO-4-NO2C6H3S]+, 105
(27), 77 (25). Found, %: C 52.81, 52.75; H 2.71,
2.84. C14H8N2O5S. Calculated, %: C 53.16, H 2.53.
149.8, 150.2 (C2), 153.4. Mass spectrum, m/z (Irel, %):
490 (68) M+, 192 (14), 167 (12), 166 (36), 165
(100.0), 137 (22), 87 (10), 73 (15), 45 (24). Found,
%: C 58.54; H 5.40. M+ 490.1120. C24H38O2S. Cal-
culated, %: C 58.76; H 5.34. M 490.1120.
2,7,10,13,24,27,30,33,36,44-Decaoxa-4,16-dithia-
pentacyclo[35.3.1.13,40.117,20.119,23]tetratetraconta-
1(40),3(42),17,19,21,23(43),37(41),38-octaene (VII).
A mixture of 0.70 g (24.5 mmol) of sodium hydride
(as 80% suspension in mineral oil) and 200 ml of
tetrahydrofuran was stirred for 30 min, and a solution
of 0.6 g (1.22 mmol) of compound VI in 200 ml of
tetrahydrofuran was added dropwise. The mixture was
heated to 65 C, and a solution of 0.74 g (1.47 mmol)
of tetraethylene glycol bis(p-toluenesulfonate) in
200 ml of THF was added dropwise over a period of
12 h. The mixture was stirred for 72 h at 65 C and
cooled to room temperature, several drops of water
were added, and the mixture was evaporated under
reduced pressure. The residue was treated with a mix-
ture of 200 ml of toluene and 100 ml of water, and the
organic phase was separated and washed in succession
with 50 ml of 0.5 N aqueous sodium hydroxide, 80 ml
of 2 N hydrochloric acid, and 2 100 ml of water.
The solvent was removed under reduced pressure, and
2-(2,4-Dinitrophenylthio)-6-methylbenzofuran
(VIIIb) was synthesized in a similar way from 0.5 g
(2.6 mmol) of thiadiazole IIId, 0.45 g (3.3 mmol) of
K2CO3, and 0.52 g (2.6 mmol) of 2,4-dinitrochloro-
benzene. The product was isolated by chromatography
on a 3 20-cm column charged with silica gel
L 40/100 m (eluent chloroform hexane, 1:1). Yield
0.51 g (59%); mp 156 161 C (from CHCl3 hexane);
1
Rf 0.66 (eluent CHCl3). H NMR spectrum (CDCl3),
, ppm: 2.52 s (CH3), 7.13 d (4-H), 7.18 d (5-H),
7.32 s (3-H), 7.34 s (7-H), 7.55 d (6-H, dinitrophenyl),
8.19 d.d (5-H, dinitrophenyl), 9.11 d (3-H, dinitro-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 10 2002

4-(2-HYDROXYARYL)-1,2,3-THIADIAZOLES
1517
1
phenyl). 13C NMR spectrum (CDCl3), C, ppm: 22.3
(CH3), 112.3, 119.8, 121.7, 121.8, 125.6, 125.9,
127.7, 129.9, 138.0, 142.2, 144.6, 145.6, 145.6,
158.3. Mass spectrum, m/z (Irel, %): 330 (14) M+, 183
(21) [M 2-oxobenzofuran]+, 147 (100) [M 2-NO-4-
NO2C6H3S]+, 91 (14), 49 (8). Found, %: C 54.31,
54.59; H 3.31, 3.24. C15H10N2O5S. Calculated, %:
C 54.54, H 3.03.
added, and H NMR spectra of the resulting mixture
were recorded at 18 C on a Bruker AMX-400 spec-
trometer (400 MHz). After 5 min, the formation of
phenoxide ion XI was detected: the hydroxy proton
signal at 9.69 ppm disappeared, and the 5-H signal
(thiadiazole ring) shifted downfield from
9.76 ppm. The signals from the phenyl protons, 3-H,
4-H, 5-H, and 6-H displaced upfield by 0.42, 0.34,
9.2 to
0.64, and 0.17 ppm, respectively. A weak evolution
of nitrogen was observed, and after 21 h the spectrum
contained signals from a 1:1 mixture of phenoxide
XI and o-hydroxyphenylethynethiolate (XIII). The
proton in position 5 of the thiadiazole ring is partially
replaced by deuterium, which confirms the formation
of anion XII. The reaction was complete in 93 h, and
2-(2,4-Dinitrophenylthio)-5-methylbenzofuran
(VIIIc) was synthesized in a similar way from 0.5 g
(2.6 mmol) of thiadiazole IIIe, 0.45 g (3.3 mmol) of
K2CO3, and 0.52 g (2.6 mmol) of 2,4-dinitrochloro-
benzene. The product was isolated by chromatography
on a 3 20-cm column charged with silica gel
L 40/100 m (eluent chloroform hexane, 1:1). From
the first fraction we isolated 0.4 g (46%) of benzo-
furan VIIIc; mp 168 170 C (from CHCl3 hexane);
1
the H NMR spectrum of the final solution contained
only signals from 2-benzofuranthiolate (X), , ppm:
5.98 s (3-H), 6.81 t and 6.90 t (5-H, 6-H), 7.06 d
(4-H, 7-H). When the reaction was carried out in
1
Rf 0.73 (eluent CHCl3). H NMR spectrum (CDCl3),
, ppm: 2.49 s (CH3), 7.12 d (7-H), 7.26 d (6-H),
7.3 s (3-H), 7.46 s (4-H), 7.42 d (6-H, dinitrophenyl),
8.19 d.d (5-H, dinitrophenyl), 9.11 d (3-H, dinitro-
1
DMSO-d6, after 15 min the H NMR spectrum con-
tained signals belonging to phenoxide ion XI (35%),
o-hydroxyphenylethynethiolate (XIII) (48%), and
2-benzofuranthiolate (X) (17%). In the 13C NMR
spectrum, signals from o-hydroxyphenylethynethiolate
phenyl). 13C NMR spectrum (CDCl3), C, ppm: 21.2
(CH3), 111.4, 119.2, 121.3, 121.4, 127.3, 127.8,
128.3, 129.5, 133.6, 142.6, 144.2, 145.1, 145.2,
155.8. Mass spectrum, m/z (Irel, %): 330 (21) M+, 183
(28) [M 2-oxobenzofuran]+, 147 (100) [M 2-NO-4-
NO2C6H3S], 119 (15), 91 (20). Found, %: C 54.24,
54.56; H 3.27, 3.34. C15H10N2O5S. Calculated, %:
C 54.54, H 3.03.
(XIII) appeared at
71.8 (d, C CS) and 101.2 ppm
C
(C CS). After 3 h, the signals belonging to phen-
oxide XI disappeared, and those corresponding to
a 1 : 1 mixture of o-hydroxyphenylethynethiolate
(XIII) and 2-benzofuranthiolate (X) were observed.
13C NMR spectrum of 2-benzofuranthiolate (X)
From the second fraction we isolated 0.14 g (11%)
of 3-(2,4-dinitrophenyl)-2-(2,4-dinitrophenylthio)-5-
methylbenzofuran (IX); mp 186 191 C (from CHCl3
cyclohexane); Rf 0.43 (eluent CHCl3). 1H NMR spec-
trum (CDCl3), , ppm: 2.42 s (CH3), 7.22 s (4-H),
7.33 d (6-H), 7.4 s (5-H), 7.65 d (6-H, C6H3S),
8.08 d (6-H, 3-C6H3), 8.43 d.d (5-H, C6H3S), 8.67 d.d
(5-H, 3-C6H3), 8.93 d (3-H, C6H3S), 8.94 d (3-H,
1
(DMSO-d6), C, ppm: 99.1 d (C3, JCH = 173 Hz),
2
173.9 d (C2, JCH = 9 Hz). The reaction was complete
1
in 7 days, and the final H NMR spectrum contained
only signals of 2-benzofuranthiolate (X).
REFERENCES
3-C6H3). 13C NMR spectrum (CDCl3), C, ppm: 20.9
(CH3), 111.9, 119.5, 120.5, 121.4, 126.7, 127.2,
128.0, 128.3, 129.0, 129.5, 130.5, 134.0, 134.8,
140.6, 141.9, 143.9, 135.3, 147.9. 148.5, 154.5. Mass
spectrum, m/z (Irel, %): 486 (46) M+, 313 (100) [M
2-NO-4-NO2C6H3S]+, 269 (14), 237 (35), 223 (34),
206 (43), 195 (59), 183 (98) [2-NO-4-NO2C6H3S]+,
178 (59), 166 (78), 139 (30), 115 (14), 85 (17), 75
(21), 63 (29). Found, %: C 50.53, 54.68; H 2.71, 2.82.
C21H12N4O9S. Calculated, %: C 50.81, H 2.42.
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ampule was charged with a solution of 4-(2-hydroxy-
phenyl)-1,2,3-thiadiazole (IIIa) in CD3CN, an equim-
olar amount of tetrabutylammonium hydroxide was
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