Synthesis of heterocycles on the basis of arylation products of unsaturated compounds: XX. Reaction of 2-aryl-1,4-benzoquinones with potassium O-butyl carbonodithioate

Article abstract of DOI:10.1134/S1070428010030164

Reactions of 2-aryl-1,4-benzoquinones with potassium O-butyl carbonodithioate gave the corresponding 7-aryl-5-hydroxy-1,3-benzoxathiole-2- thiones. In some cases, 7-aryl-5-hydroxy-1,3-benzoxathiol-2-ones were also formed.

Full text of DOI:10.1134/S1070428010030164

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 3, pp. 394–398. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © R.L. Martyak, N.D. Obushak, V.S. Matiichuk, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 3, pp. 401–404.
Synthesis of Heterocycles on the Basis of Arylation Products
of Unsaturated Compounds: XX.* Reaction of 2-Aryl-1,4-benzo-
quinones with Potassium O-Butyl Carbonodithioate
R. L. Martyak, N. D. Obushak, and V. S. Matiichuk
Ivan Franko Lviv National University, ul. Kirilla i Mefodiya 6, Lviv, 79005 Ukraine
e-mail: obushak@in.lviv.ua
Received October 16, 2008
Abstract—Reactions of 2-aryl-1,4-benzoquinones with potassium O-butyl carbonodithioate gave the corre-
sponding 7-aryl-5-hydroxy-1,3-benzoxathiole-2-thiones. In some cases, 7-aryl-5-hydroxy-1,3-benzoxathiol-
2-ones were also formed.
DOI: 10.1134/S1070428010030164
Reactions of 1,4-quinones with nucleophilic re-
agents, in particular with nitrogen-, sulfur-, oxygen-,
and carbon-centered nucleophiles, play an important
role in the chemistry of these compounds [2–5]. Such
reactions generally follow 1,4-addition pattern, leading
to the formation of hydroquinone or 1,4-benzoquinone
derivatives which may be used in practice or as rea-
gents in organic synthesis. If a nucleophile possesses
two or more functional groups, its reactions with
1,4-quinones do not stop at the addition step but in-
volve subsequent intramolecular cyclization leading to
benzo-fused heterocyclic compounds [3]. Just that pat-
tern is typical of quinone reactions with difunctional
sulfur-centered nucleophiles [3, 6–9]. However, only
reactions with unsubstituted 1,4-benzoquinone were
studied in detail. Analogous reactions with monosub-
stituted quinones may be complicated due to possible
formation of different regioisomers. For example,
halogen-substituted quinones were reported to react
with thiourea to produce mixtures of three isomeric
halogen-substituted 5-hydroxy-1,3-benzoxathiol-2-
ones [10]. Reactions of alkylquinones with thiourea
were also nonselective [10, 11]. On the whole, the
regioselectivity of reactions of monosubstituted
1,4-benzoquinones with sulfur-centered nucleophiles
was studied poorly [3, 4]. Also, a few published data
are available on reactions of nucleophiles with 2-aryl-
1,4-benzoquinones, though the latter can readily be
obtained by arylation of 1,4-benzoquinone with arene-
diazonium chlorides [12, 13] or other reagents
[14–16]. We previously showed that reactions of
2-aryl-1,4-benzoquinones with thiourea in acid medi-
um are selective [17]: nucleophilic attack is directed at
position 6 of the quinone ring. Intermediate thiuronium
salt thus formed undergoes intramolecular cyclization
with formation of 7-aryl-5-hydroxy-1,3-benzoxathiol-
2-ones. The reactions of 2-aryl-1,4-benzoquinones
with dithiols gave 1,3-benzodithiole or 1,3-benzoxa-
thiole derivatives, depending on the substituent in the
aromatic ring [18]. In the present work we examined
reactions of 2-aryl-1,4-benzoquinones with potassium
O-butyl carbonodithioate.
Scheme 1.
O
Ar
Ar
Ar
HO
Ar
S
O
S
S
O
S
+
+
+
S
S
S
BuO
SK
O
HO
HO
O
I
II
A
B
C
* For communication XIX, see [1].
394

SYNTHESIS OF HETEROCYCLES ON THE BASIS OF ARYLATION PRODUCTS ... XX.
395
Scheme 2.
O
Ar
Ar
Ar
Ar
HO
S
O
S
S
O
S
+
+
+
S
S
O
BuO
SK
O
HO
HO
O
Ia–Ig
II
IIIa–IIIg
IVa
Va–Vc
I, III, Ar = 4-BrC6H4 (a), 4-ClC6H4 (b), 3,5-Cl2C6H3 (c), 4-O2NC6H4 (d), 4-MeC6H4 (e), 4-MeOC6H4 (f), 3-F3CC6H4 (g);
IVa, Ar = 4-O2NC6H4; V, Ar = 4-MeC6H4 (a), 4-MeOC6H4 (b), 3-F3CC6H4 (c).
We have found that reactions of 2-aryl-1,4-benzo-
quinones Ia–Ig with potassium O-butyl carbonodi-
thioate (II) on heating in acetic acid for a short time
lead to the formation of 1,3-benzoxathiole-2-thiones.
Theoretically, three isomeric compounds A–C
(Scheme 1) could be formed, depending on the regio-
selectivity of primary addition of nucleophile II to
quinones I. The reactions of arylquinones with thio-
urea gave 7-aryl-5-hydroxy-1,3-benzoxathiol-2-ones as
analogs of isomer A [17]. Analysis of the 1H NMR and
mass spectra of the products showed that 2-aryl-1,4-
benzoquinones Ia–Ig reacted with potassium O-butyl
carbonodithioate less selectively than with thiourea. In
all cases, 7-aryl-5-hydroxy-1,3-benzoxathiole-2-
thiones IIIa–IIIg (isomer A) were the major products
(Scheme 2). In the reactions of arylquinones Ia–Ic
with KSC(=S)OBu, other cyclization products were
also formed in insignificant amounts, and compounds
IIIa–IIIc were readily isolated by recrystallization.
The reactions of arylquinones Id–Ig with potassium
O-butyl carbonodithioate (II) gave two products in
comparable amounts. For example, the major product
in the reaction of 2-(4-nitrophenyl)-1,4-benzoquinone
(Id) with nucleophile II was compound IVa (isomer B;
J6,7 = 7.6 Hz). Arylquinones Ie–Ig reacted with II to
form compounds IIIe–IIIg as the major products and
significant amounts of 7-aryl-5-hydroxy-1,3-benzoxa-
thiol-2-ones Va–Vc. 1,3-Benzoxathiol-2-ones V were
also formed in the reactions with quinones Ia–Ic, but
their yields were very poor (2–3%). The product ratios
in the reactions of Id–Ig with II are listed below: Id
(R = 4-O2N), IIId : IVa = 30 : 70; Ie (R = 4-Me),
IIIe:Va = 50:50; If (R = 4-MeO), IIIf:Vb = 75:25;
Ig (R = 3-F3C), IIIg:Vc = 65:35.
Thus the main reaction direction is nucleophilic
attack by the anionic sulfur atom of potassium O-butyl
carbonodithioate at position 6 of the quinone ring. This
is confirmed by the long-range coupling constant for
the 4-H and 6-H protons (J = 2.0–2.4 Hz) appearing in
1
the H NMR spectrum as two doublets. Obviously,
compound IVa is formed as a result of primary nu-
cleophile addition at C3 (ortho position with respect to
the aryl substituent), which is likely to be favored by
electron-withdrawing effect of the nitro group.
Scheme 3 shows a probable mechanism of formation
of cyclization products III and V. Addition product of
potassium O-butyl carbonodithioate (II) to arylquinone
I, substituted hydroquinone VI, undergoes cyclization
to thiones III via intramolecular transesterification.
Unexpected formation of benzoxathiol-2-ones Va–Vc
Scheme 3.
Ar
O
S
S
–BuOH
OH
OH
OH
OH
HO
Ar
Ar
S
OBu
Ar
S
OH
IIIa–IIIg
H+
–BuOH
S
S
OH
Ar
S
O
O
S
O
VI
VII
SH
–H2S
HO
OH
VIII
Va–Vc
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 3 2010

MARTYAK et al.
396
Scheme 4.
S
S
Br
Br
O
O
O
S
S
+
R
Cl
OH
OCOR
IIIa
IXa–IXc
Xa–Xc
R = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4CH=CH (c).
may be rationalized assuming hydrolysis of butyl ester
VI to carbonodothioic O-acid VII, followed by thione–
thiol isomerization VII →VIII and intramolecular
cyclization. Thiones IIIa–IIIg can also be formed
through intermediate VII.
2.0 Hz), 7.61 d (2H, C6H4, J = 8.1 Hz), 7.74 d (2H,
C6H4, J = 8.1 Hz), 10.14 s (1H, OH). Mass spectrum,
m/z (Irel, %): 340/338 (100) [M]+, 199 (27), 183 (70),
171 (48), 155 (36), 127 (55), 115 (20), 101 (30).
Found, %: C 45.84; H 2.01; S 19.12. C13H7BrO2S2.
Calculated, %: C 46.03; H 2.08; S 18.90. M 339.23.
Compounds IIIa–IIIg readily undergo acylation
with carboxylic acid chlorides in the presence of
a base. The reaction of IIIa with acid chlorides IXa–
IXc gave the corresponding O-acyl derivatives Xa–Xc
(Scheme 4).
7-(4-Chlorophenyl)-5-hydroxy-1,3-benzoxa-
thiole-2-thione (IIIb). Yield 51%, mp 211–212°C
1
(from MeOH–H2O, 1:1). H NMR spectrum, δ, ppm:
6.95 d (1H, 4-H, J4,6 = 2.3 Hz), 7.19 d (1H, 6-H, J4,6
=
2.3 Hz), 7.60 d (2H, C6H4, J = 8.4 Hz), 7.68 d (2H,
C6H4, J = 8.4 Hz), 10.15 s (1H, OH). Mass spectrum,
m/z (Irel, %): 296 (44), 294 (100) [M]+, 183 (30), 171
(25), 162 (18), 115 (10). Found, %: C 53.21; H 2.48;
S 21.91. C13H7ClO2S2. Calculated, %: C 52.97; H 2.39;
S 21.75. M 294.78.
EXPERIMENTAL
The 1H NMR spectra were recorded on Bruker WP-
300 (300 MHz; IIIb, IIId–IIIg, IVa, Va–Vc) and
Bruker DRX-500 spectrometers (500 MHz; IIIa, IIIc,
Xa–Xc) using DMSO-d6 as solvent and tetramethyl-
silane as internal reference. The mass spectra (electron
impact, 70 eV) were obtained on a Finnigan MAT
Incos-50 GC–MS system.
7-(3,5-Dichlorophenyl)-5-hydroxy-1,3-benzoxa-
thiole-2-thione (IIIc, 1:1 solvate with DMF). Yield
69%, mp 238–239°C (from EtOH–DMF, 3:1). 1H NMR
spectrum, δ, ppm: 7.09 d (1H, 4-H, J4,6 = 2.4 Hz),
7.44–7.50 m (3H, 6-H, C6H3), 7.58 s (1H, C6H3),
10.24 s (1H, OH); DMF signals: 2.75 s (3H, CH3),
2.92 s (3H, CH3), 7.94 s (1H, CHO). Mass spectrum,
m/z (Irel, %): 332 (15), 330 (65), 328 (100) [M]+, 233
(38), 205 (36), 198 (13), 170 (12), 126 (14). Found, %:
C 47.45; H 3.11; S 16.12. C13H6Cl2O2S2·C3H7NO. Cal-
culated, %: C 47.77; H 3.26; S 15.94. M 329.23.
Initial 2-aryl-1,4-benzoquinones Ia–Ig were synthe-
sized as described in [12, 13, 18–20].
Reaction of 2-aryl-1,4-benzoquinones Ia–Ig with
potassium O-butyl carbonodithioate (II) (general
procedure). A suspension of 10 mmol of 2-aryl-1,4-
benzoquinone Ia–Ig in 20 ml of glacial acetic acid was
added under stirring to a solution of 2.1 g (11 mmol) of
potassium O-butyl carbonodithioate (II) in 10 ml of
water. The mixture was heated for 30 min at the
boiling point under stirring and cooled, and the precip-
itate was filtered off, washed with several portions of
water and with alcohol, and dried. The crude product
was analyzed by gas chromatography–mass spectrom-
5-Hydroxy-7-(4-nitrophenyl)-1,3-benzoxathiole-
1
2-thione (IIId). Yield 26%. H NMR spectrum, δ,
ppm: 7.03 d (1H, 4-H, J4,6 = 2.1 Hz), 7.28 d (1H, 6-H,
J4,6 = 2.1 Hz), 7.97 d (2H, C6H4, J = 7.8 Hz), 8.39 d
(2H, C6H4, J = 7.8 Hz), 10.25 s (1H, OH).
5-Hydroxy-4-(4-nitrophenyl)-1,3-benzoxathiole-
1
1
etry and H NMR to identify particular isomers and
determine their ratio.
2-thione (IVa). Yield 58%. H NMR spectrum, δ,
ppm: 7.15 d (1H, 6-H, J6,7 = 7.6 Hz), 7.59 d (1H, 7-H,
J6,7 = 7.6 Hz), 7.80 d (2H, C6H4, J = 7.8 Hz), 8.33 d
(2H, C6H4, J = 7.8 Hz), 10.48 s (1H, OH); Mass spec-
trum of mixture IIId/IVa, m/z (Irel, %): 305 (100) [M]+,
258 (11), 198 (13), 171 (22), 155 (18), 126 (25), 115
7-(4-Bromophenyl)-5-hydroxy-1,3-benzoxa-
thiole-2-thione (IIIa). Yield 61%, mp 215–216°C
1
(from EtOH–H2O, 1:1). H NMR spectrum, δ, ppm:
6.95 d (1H, 4-H, J4,6 = 2.0 Hz), 7.19 d (1H, 6-H, J4,6
=
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SYNTHESIS OF HETEROCYCLES ON THE BASIS OF ARYLATION PRODUCTS ... XX.
397
(16). Found, %: C 51.10; H 2.23; N 4.70; S 21.21.
C13H7NO4S2. Calculated, %: C 51.14; H 2.31; N 4.59;
S 21.00. M 305.33.
and the mixture was heated for 1 h with stirring under
reflux. The mixture was cooled, the precipitate was
filtered off, the filtrate was evaporated, and the residue
was washed several times with water and purified by
recrystallization.
5-Hydroxy-7-(4-methylphenyl)-1,3-benzoxa-
thiole-2-thione (IIIe) and 5-hydroxy-7-(4-methyl-
phenyl)-1,3-benzoxathiol-2-one (Va) (1:1 mixture).
Yield 56%. 1H NMR spectrum, δ, ppm: 2.36 s (1.5H,
7-(4-Bromophenyl)-2-thioxo-1,3-benzoxathiol-
5-yl benzoate (Xa). Yield 53%, mp 175–176°C (from
1
EtOH–DMF, 2:1). H NMR spectrum, δ, ppm: 7.45 d
Me), 2.37 s (1.5H, Me), 6.85 d (0.5H, 4-H, J4,6
=
(1H, 4-H, J4,6 = 2.1 Hz), 7.58 t (2H, C6H4, J = 8.0 Hz),
2.4 Hz), 6.93 d (0.5H, 4-H, J4,6 = 2.1 Hz), 7.13 m (1H,
6-H), 7.25–7.39 m (2H, C6H4), 7.47–7.58 m (2H,
C6H4), 9.89 s (0.5H, OH), 10.11 s (0.5H, OH). Mass
spectrum, m/z (Irel, %): 274 (100) [M]+ (IIIe), 258 (90)
[M]+ (Va), 214 (17), 202 (45), 171 (12), 142 (15), 115
(27). Found, %: C 63.33; H 3.90; S 17.89. Calculated
for IIIe/Va (1:1), %: C 63.14; H 3.78; S 18.06.
M 274.36 (IIIe), 258.30 (Va).
7.62–7.72 m (5H, C6H5), 7.66 d (1H, 6-H, J4,6
=
2.1 Hz), 8.17 d (2H, C6H4, J = 7.8 Hz). Mass spectrum,
m/z (Irel, %): 444/442 (67) [M]+, 428/426 (12), 105
(100), 77 (37). Found, %: C 54.02; H 2.45; S 14.28.
C20H11BrO3S2. Calculated, %: C 54.18; H 2.50;
S 14.46. M 443.34.
7-(4-Bromophenyl)-2-thioxo-1,3-benzoxathiol-5-
yl 4-methylbenzoate (Xb). Yield 66%, mp 182–183°C
(from EtOH–DMF, 2:1). H NMR spectrum, δ, ppm:
5-Hydroxy-7-(4-methoxyphenyl)-1,3-benzoxa-
thiole-2-thione (IIIf) and 5-hydroxy-7-(4-methoxy-
phenyl)-1,3-benzoxathiol-2-one (Vb) (3:1 mixture).
1
7.36 d (2H, C6H4, J = 7.7 Hz), 7.43 d (1H, 4-H, J4,6
=
1
2.1 Hz), 7.64 d (1H, 6-H, J4,6 = 2.1 Hz), 7.68 s (4H,
C6H4), 8.05 d (2H, C6H4, J = 7.8 Hz). Mass spectrum,
m/z (Irel, %): 458/456 (46) [M]+, 442/440 (10), 119
(100), 91 (28). Found, %: C 55.34; H 2.96; S 13.88.
C21H13BrO3S2. Calculated, %: C 55.15; H 2.87;
S 14.02. M 457.37.
Yield 35 and 12% respectively. H NMR spectrum, δ,
ppm: 3.82 s (0.75H, MeO), 3.83 s (2.25H, MeO),
6.83 d (0.25H, 4-H, J4,6 = 2.4 Hz), 6.92 d (0.75H, 4-H,
J4,6 = 2.5 Hz), 7.04–7.15 m (3H, 6-H, C6H4), 7.53–
7.64 m (2H, C6H4), 9.87 s (0.25H, OH), 10.08 s
(0.75H, OH). Mass spectrum, m/z (Irel, %): 290 (100)
[M]+ (IIIf), 274 (45) [M]+ (Vb), 246 (15), 218 (37),
203 (40), 187 (13), 158 (14), 143 (15), 115 (33).
Found, %: C 58.97; H 3.67; S 19.35. Calculated for
IIIf/Vb (3:1), %: C 58.72; H 3.52; S 19.59. M 290.36
(IIIf), 274.30 (Vb).
7-(4-Bromophenyl)-2-thioxo-1,3-benzoxathiol-
5-yl (2E)-3-(4-methoxyphenyl)prop-2-enoate (Xc).
Yield 59%, mp 226–227°C (from EtOH–DMF, 2:1).
1H NMR spectrum, δ, ppm: 3.83 s (3H, MeO), 6.72 d
(1H, 3′-H, J = 15.0 Hz), 6.96 d (2H, C6H4, J = 7.6 Hz),
7.42 d (1H, 4-H, J4,6 = 2.0 Hz), 7.54 d (2H, C6H4, J =
7.6 Hz), 7.62 d (1H, 6-H, J4,6 = 2.0 Hz), 7.63 d (1H,
2′-H, J 15.0 Hz), 7.66–7.70 m (4H, C6H4). Mass spec-
trum, m/z (Irel, %): 500/498 (25) [M]+, 161 (100), 133
(16), 119 (15). Found, %: C 55.45; H 2.97; S 12.73.
C23H15BrO4S2. Calculated, %: C 55.32; H 3.03;
S 12.84. M 499.41.
5-Hydroxy-7-(3-trifluoromethylphenyl)-1,3-
benzoxathiole-2-thione (IIIg) and 5-hydroxy-7-(3-
trifluoromethylphenyl)-1,3-benzoxathiol-2-one (Vc)
(65:35 mixture). Yield 39 and 21%, respectively.
1H NMR spectrum, δ, ppm: 6.93 d (0.35H, 4-H, J4,6
=
2.1 Hz), 7.02 d (0.65H, 4-H, J4,6 = 2.1 Hz), 7.20 m
(1H, 6-H), 7.72–7.88 m (2H, C6H4), 7.90–8.04 m (2H,
C6H4), 9.99 s (0.35H, OH), 10.19 s (0.65H, OH). Mass
spectrum, m/z (Irel, %): 328 (100) [M]+ (IIIg), 312 (30)
[M]+ (Vc), 268 (14), 256 (48), 196 (20), 171 (23), 151
(20), 85 (30). Found, %: C 52.32; H 2.28; S 16.53.
Calculated for IIIg/Vc (65:35), %: C 52.11; H 2.19;
S 16.39. M 328.33 (IIIg), 312.27 (Vc).
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