CuI-catalyzed thioarylation of active methylene compounds with in situ generated benzenethiols: Preparation of α-thioaryl-β-dicarbonyls and 4-thioaryl-5-pyrazolones

Article abstract of DOI:10.1016/j.tet.2018.07.049

In this paper, a one-step copper-catalyzed procedure for oxidative coupling of active methylene compounds including cyclic β-diketones, cyclic β-ketoesters and 5-pyrazolone with benzenethiols is described. Benzenethiols are in situ generated in the reaction mixture from aryl halides and thiourea as sulfur transfer reagent. α-Thioaryl compounds are obtained in excellent yields and in short reaction time via the process which is free from the foul smell of thiols.

Full text of DOI:10.1016/j.tet.2018.07.049

Tetrahedron xxx (2018) 1e9
Contents lists available at ScienceDirect
Tetrahedron
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CuI-catalyzed thioarylation of active methylene compounds with in
situ generated benzenethiols: Preparation of
and 4-thioaryl-5-pyrazolones
a-thioaryl-b-dicarbonyls
Nooshin Golzar, Najmeh Nowrouzi*, Mohammad Abbasi
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, a one-step copper-catalyzed procedure for oxidative coupling of active methylene com-
pounds including cyclic -diketones, cyclic -ketoesters and 5-pyrazolone with benzenethiols is
described. Benzenethiols are in situ generated in the reaction mixture from aryl halides and thiourea as
sulfur transfer reagent. -Thioaryl compounds are obtained in excellent yields and in short reaction time
via the process which is free from the foul smell of thiols.
Received 26 February 2018
Received in revised form
23 July 2018
Accepted 25 July 2018
Available online xxx
b
b
a
© 2018 Published by Elsevier Ltd.
Keywords:
Copper-catalyzed
Sulfur transfer reagent
b
-Diketones
Oxidative coupling
-Thioaryl- -dicarbonyls
a
b
5-Pyrazolone
1. Introduction
nucleophiles with active methylene compounds in the presence of
carbon tetrabromide [9]. Also, the iodine-catalyzed oxidative
Sulfur functionalities are important building blocks in organic
synthesis. They are important industrial compounds used in the
agrochemicals, pharmaceutical and cosmetic industries as well as
coupling between 1,3-diketones and thiophenols to afford b-
dicarbonyl thioethers was recently described by Hu and co-workers
[10].
in the manufacture of polymers [1]. Among them,
a
-thioaryl-
b
-
Despite extensive efforts in the sulfenylation of indole [11] and
imidazole [12] derivatives, less attention to date has been paid to
the sulfenylation of dicarbonyl compounds.
In continuation of our research on CeS coupling reactions [13],
herein, we report a novel method for odourless thioarylation of b-
diketones and pyrazolones from aryl halides in the presence of
sulfur transfer reagent. To our knowledge, there are no report
describing the sulfenylation of active methylene compounds using
aryl halides.
dicarbonyl compounds are extremely useful intermediates for the
synthesis of heterocyclic compounds and pharmaceutical products
[2]. For the formation of CeS bond between ketones and thio-
phenols, one of them need to be transformed to the corresponding
electrophiles. Thus, traditional synthetic routes for preparation of
these compounds can be divided into two categories: the nucleo-
philic substitution of a-halogenated ketones with thiophenols or
disulfides [3] and the reaction of enolates with various sulfenylat-
ing reagents, such as sulfenamides [4], thiosulfonates [5], sulfuryl
chloride [6], sulphenyl halides [7] and disulfides [8]. Since most
electrophiles are directly or indirectly prepared from their corre-
sponding nucleophiles, recently, efforts have been devoted toward
the oxidative coupling between two nucleophiles. In this way, Tan
et al. reported a new route to thioethers by reacting the sulfur
2. Results and discussion
The initial screening of the reaction conditions was conducted
using 5,5-dimethylcyclohexane-1,3-dione (dimedone) (1.0 mmol)
and 4-iodotoluene (2.0 mmol) in the presence of thiourea
(2.6 mmol), C2Cl6 (1.5 mmol), CuI (20 mol%), DMAP (20 mol%) and
Na2CO3 (2.0 mmol) at 120 ꢀC. The reaction in DMSO afforded the
desired product in 70% yield after 24 h (Table 1, entry 1). No better
* Corresponding author.
E-mail address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
https://doi.org/10.1016/j.tet.2018.07.049
0040-4020/© 2018 Published by Elsevier Ltd.
Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
benzenethiols: Preparation of
j.tet.2018.07.049
a-thioaryl-b-dicarbonyls and 4-thioaryl-5-pyrazolones, Tetrahedron (2018), https://doi.org/10.1016/

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N. Golzar et al. / Tetrahedron xxx (2018) 1e9
Table 1
Optimization of oxidative coupling reaction between dimedone (1.0 mmol) and 4-iodotoluene (2.0 mmol) under different conditions.
Entry
Catalyst (mol%)
Solvent
Base (2.0 mmol)
T (oC)
Time (h)
Yield (%)a
1
2
3
CuI (20)
CuI (20)
CuI (20)
DMSO
PEG-200
H2O
Na2CO3
Na2CO3
Na2CO3
120
120
100
24
24
24
70
45
e
4
CuI (20)
Toluene
Na2CO3
reflux
24
e
5
6
7
8
CuI (30)
CuI (15)
CuI (10)
DMSO
DMSO
DMSO
DMSO
Na2CO3
Na2CO3
Na2CO3
Na2CO3
120
120
120
120
24
24
24
24
70
41
25
e
e
9
10
CuCl (20)
CuCl2 (20)
DMSO
DMSO
Na2CO3
Na2CO3
120
120
24
24
trace
e
11
Cu(OAc)2 (20)
DMSO
Na2CO3
120
24
e
12
13
14
15
16
17
18
19b
Cu(PPh3)3I (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Na2CO3
K2CO3
Bu3N
120
120
120
120
120
100
130
120
24
24
24
5
15 min
24
15 min
24
55
75
40
90
93
64
93
KOH
KOH (4.0)
KOH (4.0)
KOH (4.0)
KOH (4.0)
e
a
Isolated yield.
The reaction was carried out in the absence of C2Cl6.
b
results were obtained, when the reaction was carried out in poly-
ethylene glycol (PEG-200, 120 ꢀC), H2O (100 ꢀC) or in refluxing
toluene (Table 1, entries 2e4). Therefore, the subsequent reactions
were performed in DMSO. No further yield improvement is ach-
ieved using higher concentration of ligand or/and substrates or
increasing the catalyst loading. On the other hand, reducing the
amount of CuI, greatly reduced the reaction yield (Table 1, entries 6
and 7). As expected, in the absence of catalyst, no product was
formed (Table 1, entry 8). Performing the reaction in the presence of
other Cu-catalysts such as CuCl, CuCl2, Cu(OAc)2 and Cu(PPh3)3I
showed that the appropriate choice of catalyst was CuI (Table 1,
entries 9e12). Next, alternative bases such as K2CO3, Bu3N, KOH
were screened, however in these cases, KOH is the best, providing
product in 93% isolated yield within 15 min (Table 1, entries 13e16).
A temperature of 120 ꢀC was found to be the optimal reaction
temperature. Decreasing the temperature, resulted the product in
lower yield (Table 1, entry 17) and higher temperature (Table 1,
entry 18) did not have any significant effect on the conversion; The
sulfenylation carried out at 100 and 130 ꢀC, afforded 64% and 93%
yields respectively. Finally, we observed that no sulfenylation
product was detected in the absence of C2Cl6 (Table 1, entry 19).
We then applied the obtained optimized conditions (dicarbonyl
compound (1.0 mmol), aryl halide (2.0 mmol), thiourea (2.6 mmol),
C2Cl6 (1.5 mmol), CuI (20 mol%), DMAP (20 mol%) and KOH
(4.0 mmol) in DMSO at 120 ꢀC), for the reaction of different aryl
iodides with active methylene compounds in the presence of sulfur
transfer reagent. The results are summarized in Table 2.
excellent yields. Electronically different aryl iodides were also
proved to be very efficient and in these cases, the corresponding
sulfenylated products were obtained in excellent yields (Table 2,
entries 1e18). The aryl iodides functionalized with ortho sub-
stituents demonstrated viable reactivity, suggesting that steric
factors on the arene group of halides do not apply a limitation for
the product formation.
To further extend the substrate scope, various active methylene
compounds such as malononitrile, methyl 2-cyanoacetate, ethyl 2-
cyanoacetate, ethyl 3-oxobutanoate (Table 2, entries 19e22) were
treated with p-iodoanisole under the optimized reaction condi-
tions. However, with this substrate combination, the expected CeS
bond formation did not occur and in all cases, the corresponding
disulfide was formed as the sole product in the reaction mixture.
Unexpectedly, when linear b-diketone such as pentane-2,4-dione
was used as the coupling partners, no product was formed
(Table 2, entry 23). The only difference between these structures
(linear and circle) after the reaction with copper iodide is the for-
mation of a six-membered chelate ring in linear structures that
cannot be formed in the circles. But, it is not clear to us whether this
difference is involved in the formation of cyclic products. As shown
in entry 24 of Table 2, simple ketone enolates are not sufficiently
reactive toward thioarylation by the use of our catalytic system;
when acetophenone was allowed to react with p-iodoanisole under
the optimized reaction conditions, no product was detected even
after prolonged reaction time. After the successful application of
this methodology for different aryl iodides, we studied the appli-
cability of this catalytic system for the reaction of aryl bromides
under the obtained optimized reaction conditions. As summarized
The reactions of cyclic
1,3-dione and cyclohexane-1,3-dione), cyclic
mane-2,4-dione and 6-methyl-2H-pyran-2,4(3H)-dione) and 5-
methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one with iodo-
b
-diketones (5,5-dimethylcyclohexane-
b-ketoesters (chro-
in Table 3, couplings of different aryl bromides with cyclic
b-dike-
tones, cyclic -ketoesters and pyrazolones for the preparation of
b
benzene proceeded smoothly in accordance with the optimized
reaction conditions, affording the corresponding products in
desired products, found to be facile, generating high yields (Table 3,
entries 1e13).
Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
benzenethiols: Preparation of
j.tet.2018.07.049
a-thioaryl-b-dicarbonyls and 4-thioaryl-5-pyrazolones, Tetrahedron (2018), https://doi.org/10.1016/

N. Golzar et al. / Tetrahedron xxx (2018) 1e9
3
Table 2
The scope of thioarylation of active methylene compounds with aryl iodides.a
Entry
1
Active methylene compound
ArI
Time (min)
18
Yield (%)b
91 [14]
2
3
15
17
93 [14]
95
4
26
91
5
6
25
20
86
89
7
23
86
8
9
24
21
91
94 [15]
10
11
18
19
92 [15]
85
(continued on next page)
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N. Golzar et al. / Tetrahedron xxx (2018) 1e9
Table 2 (continued )
Entry
12
Active methylene compound
ArI
Time (min)
20
Yield (%)b
88 [15]
13
14
15
16
17
14
12
27
92 [16]
98
90
80 [17]
17
24
87 [17]
18
26
90 [17]
19
20
21
22
24 h
24 h
24 h
24 h
_
_
_
_
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N. Golzar et al. / Tetrahedron xxx (2018) 1e9
5
Table 2 (continued )
Entry
23
Active methylene compound
ArI
Time (min)
24 h
Yield (%)b
_
24
24 h
_
a
Reaction conditions: aryl iodides (2.0 mmol), active methylene compound (1.0 mmol), thiourea (2.6 mmol), C2Cl6 (1.5 mmol), CuI (20 mol%), DMAP (20 mol%), KOH
(4.0 mmol) in 2 mL DMSO at 120 ꢀC.
b
Isolated yield.
Further examination with chlorobenzene, using the above
established conditions, did not afford any sulfenylated product.
Thus, this catalytic system is not efficient for chloro arenes.
Based on these experiments, a proposed mechanism for sulfe-
nylation of active methylene compounds (1,3-diketone) is shown in
Scheme 1.
using thiourea as odourless and stable source of sulfur. A variety of
aromatic halides were used efficiently and the organic sulfide
products were obtained in good to excellent yields. Inexpensive
catalyst, one-step procedure, normal atmospheric conditions,
easily available and odourless reagents are the other advantages of
the present catalytic system.
In the first step, CuI undergoes oxidative addition by insertion
into the aryl CeX bond to produce Cu(III) species. The formed
Cu(III) species is then converted to intermediate (I) by replacement
of halide by thiourea. Reductive-elimination step, gives interme-
diate (II) along with regeneration of CuI catalyst. Hydrolysis of in-
termediates (II) in alkaline media generates the corresponding
thiolate which undergo oxidation with C2Cl6 to generate the cor-
responding arylsulfenyl chloride or diaryl disulfide.13 On the other
hand, a metal enolate species is formed in the reaction mixture by
deprotonation of 1,3-diketone in the presence of CuI and KOH as
base. The nucleophilic attack of the enolate on the reactive aryl-
sulfenyl chloride or diaryl disulfide, yields the desired sulfenylated
product.
To support the reaction mechanism, we decided to use diaryl
disulfide in place of ArI/thiourea/C2Cl6. In this way, diphenyl di-
sulfide has been prepared and its reaction with dimedone in the
presence of KOH in DMSO was carried out at 120 ꢀC. In this case, the
sulfenylated product was obtained in 89% yield after several
minutes.
3. Experimental section
3.1. General procedure for thioarylation of active methylene
compounds
Thiourea (2.6 mmol, 0.204 g), C2Cl6 (1.5 mmol, 0.355 g), DMAP
(20 mol%, 0.024 g), aryl halide (2.0 mmol), active methylene com-
pound (1.0 mmol), CuI (20 mol %, 0.038 g) and KOH (4.0 mmol,
0.224 g) were added to a flask containing 2 mL of DMSO. The
mixture was heated in an oil bath at 120 ꢀC with stirring and the
reaction was followed by TLC analysis. When the reaction was
completed, the solution was let to cool,1 mL of 1.0 M HCl was added
and stirring is continued for 2 min. Next, the product was extracted
with ethylacetate (3 ꢁ 3 mL). The solvent was removed and the
crude product was purified by chromatography over silica gel using
n-hexane/ethyl acetate as eluent to afford the pure product
(Tables 2 and 3).
In summary, we have developed a thiol-free route for the
3.2. 3-Hydroxy-5,5-dimethyl-2-phenylsulfanyl-cyclohex-2-enone
(Table 2, entry 1)
preparation of
pyrazolones via a copper-catalyzed oxidative coupling reaction
between aryl halides and cyclic -diketones, cyclic -ketoesters and
a-thioaryl-b-dicarbonyls and 4-thioaryl-5-
b
b
dH (400 MHz, CDCl3) 1.16 (s, 6H, CH3), 2.46 (s, 2H, CH2), 2.62 (s,
2H, CH2), 7.18e7.28 (m, 5H, Ar), 8.04 (s, 1H, OH). dC (100 MHz,
CDCl3) 28.2, 28.3, 31.6, 42.2, 51.0, 106.1, 126.3, 127.5, 129.1, 134.7,
178.3, 194.1.
5-pyrazolone. Carbon-Sulfur bond was formed in one-step process
3.3. 3-Hydroxy-5,5-dimethyl-2-(p-tolylthio)cyclohex-2-en-1-one
(Table 2, entry 2)
dH (400 MHz, DMSO‑d6) 1.06 (s, 6H, CH3), 2.24 (s, 3H, CH3), 2.37
(s, 2H, CH2), 2.39 (s, 2H, CH2), 6.96 (d, 2H, J ¼ 8.0 Hz, Ar), 7.05 (d, 2H,
J ¼ 8.0 Hz, Ar), 11.55 (s, 1H, OH). dC (100 MHz, DMSO‑d6) 20.9, 28.3,
29.5, 31.7, 45.1, 50.8, 103.8, 126.4, 129.7, 134.2, 137.9, 172.2, 180.3.
3.4. 3-Hydroxy-5,5-dimethyl-2-(o-tolylthio)cyclohex-2-en-1-one
(Table 2, entry 3)
dH (400 MHz, DMSO‑d6) 1.08 (s, 6H, CH3), 2.32 (s, 3H, CH3), 2.49
(s, 4H, CH2), 6.75 (d, 1H, J ¼ 7.2 Hz, Ar), 6.98 (t, 1H, J ¼ 7.2 Hz, Ar),
7.04 (t,1H, J ¼ 7.0 Hz, Ar), 7.14 (d, 1H, J ¼ 7.2 Hz, Ar),11.56 (s,1H, OH).
dC (100 MHz, DMSO‑d6) 20.0, 28.3, 31.5, 31.7, 47.5, 60.2, 102.5, 124.4,
124.7, 126.5, 130.2, 134.4, 137.4, 171.6, 189.0. Anal. Calcd for
Scheme 1. A proposed mechanism for thioarylation of active methylene compounds.
Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
benzenethiols: Preparation of
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Table 3
Sulfenylation of active methylene compounds with aryl bromides.a
Entry
1
Active methylene compound
ArBr
Time (min)
27
Yield (%)b
89 [15]
2
3
34
23
83
94 [16]
4
5
19
22
95
92 [15]
6
7
30
23
85
87
8
25
16
27
89 [15]
9
91
10
86 [17]
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N. Golzar et al. / Tetrahedron xxx (2018) 1e9
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Table 3 (continued )
Entry
11
Active methylene compound
ArBr
Time (min)
31
Yield (%)b
85 [17]
12
13
25
22
92 [14]
87
a
Reaction conditions: aryl bromides (2.0 mmol), diketone (1.0 mmol), thiourea (2.6 mmol), C2Cl6 (1.5 mmol), CuI (20 mol%), DMAP (20 mol%), KOH (4.0 mmol) in 2 mL
DMSO at 120 ꢀC.
b
Isolated yield.
(C15H18O2S): C, 68.67; H, 6.92; S, 12.22. Found: C, 68.58; H, 6.86; S,
12.33.
102.6, 123.6, 123.7, 125.9, 129.5, 133.5, 136.7, 177.6, 191.8. Anal. Calcd
for (C13H14O2S): C, 66.64; H, 6.02; S, 13.68. Found: C, 66.55; H, 6.13;
S, 13.60.
3.5. 2-((2-Chlorophenyl)thio)-3-hydroxy-5,5-dimethylcyclohex-2-
en-1-one (Table 2, entry 4)
3.9. 2-((4-Chlorophenyl)thio)-3-hydroxycyclohex-2-en-1-one
(Table 2, entry 8)
dH (400 MHz, DMSO‑d6) 1.09 (s, 6H, CH3), 2.51 (s, 2H, CH2), 2.52
(s, 2H, CH2), 6.77e6.79 (dd, 1H, J1 ¼8.0 Hz, J2 ¼ 1.6 Hz, Ar), 7.06e7.11
(dt, 1H, J1 ¼7.8 Hz, J2 ¼ 1.6 Hz, Ar), 7.16e7.21 (dt, 1H, J1 ¼7.6 Hz,
J2 ¼ 1.2 Hz, Ar), 7.39e7.41 (dd, 1H, J1 ¼8.0 Hz, J2 ¼ 1.2 Hz, Ar), 8.13 (s,
1H, OH). dC (100 MHz, DMSO‑d6) 28.3, 31.7, 34.8, 47.3, 51.1, 101.1,
125.7, 125.8, 127.7, 128.1, 129.7, 137.4, 174.2, 189.4. Anal. Calcd for
(C14H15ClO2S): C, 59.46; H, 5.35; S, 11.34. Found: C, 59.52; H, 5.30; S,
11.27.
dH (400 MHz, DMSO‑d6) 2.05e2.12 (m, 2H, CH2), 2.65e2.67 (m,
4H, CH2), 7.07 (d, 2H, J ¼ 8.4 Hz, Ar), 7.17 (d, 2H, J ¼ 8.0 Hz, Ar), 11.69
(s, 1H, OH). dC (100 MHz, DMSO‑d6) 20.6, 34.3, 34.4, 104.8, 126.3,
129.9, 134.2, 135.0, 188.6, 193.7. Anal. Calcd for (C12H11ClO2S): C,
56.58; H, 4.35; S, 12.59. Found: C, 56.67; H, 4.43; S, 12.46.
3.10. 2-Hydroxy-3-phenylsulfanyl-chromen-4-one (Table 2, entry
9)
3.6. 3-Hydroxy-2-(phenylthio)cyclohex-2-en-1-one (Table 2, entry
5)
dH (400 MHz, DMSO‑d6) 6.96e7.40 (m, 7H, Ar), 7.70 (d, 1H,
J ¼ 6.4 Hz, Ar), 7.99 (d, 1H, J ¼ 5.6 Hz, Ar). dC (100 MHz, DMSO‑d6)
116.2,118.0, 118.1, 123.4,124.5, 124.6,125.5,128.7, 132.6,137.8, 153.2,
161.9, 170.5.
dH (400 MHz, DMSO‑d6) 1.94e2.00 (m, 2H, CH2), 2.52e2.57 (m,
4H, CH2), 7.01e7.08 (m, 3H, Ar), 7.22 (t, 2H, J ¼ 7.8 Hz, Ar), 11.65 (s,
1H, OH). dC (100 MHz, DMSO‑d6) 20.4, 35.7, 36.7, 103.9, 124.6, 125.6,
129.0, 138.4, 187.3, 193.8. Anal. Calcd for (C12H12O2S): C, 65.43; H,
5.49; S, 14.55. Found: C, 65.52; H, 5.39; S, 14.47.
3.11. 4-Hydroxy-3-(p-tolylthio)-2H-chromen-2-one (Table 2, entry
10)
3.7. 3-Hydroxy-2-(p-tolylthio)cyclohex-2-en-1-one (Table 2, entry
6)
dH (400 MHz, DMSO‑d6) 2.16 (s, 3H, CH3), 6.92 (d, 2H, J ¼ 7.6 Hz,
Ar), 7.08e7.13 (m, 4H, Ar), 7.41 (t, 1H, J ¼ 7.8 Hz, Ar), 7.73 (d, 1H,
J ¼ 6.4 Hz, Ar). dC (100 MHz, DMSO‑d6) 20.9, 89.1, 116.3, 119.3, 123.3,
125.0, 127.2, 128.6, 130.2, 132.4, 138.2, 153.6, 162.6, 171.9.
dH (400 MHz, DMSO‑d6) 1.91e1.97 (m, 2H, CH2), 2.23 (s, 3H,
CH3), 2.52e2.55 (m, 4H, CH2), 6.93 (d, 2H, J ¼ 8.4 Hz, Ar), 7.03 (d, 2H,
J ¼ 8.0 Hz, Ar), 11.53 (s, 1H, OH). dC (100 MHz, DMSO‑d6) 20.4, 20.9,
34.1, 34.2, 104.6, 126.1, 129.7, 133.9, 134.8, 187.9, 194.3. Anal. Calcd
for (C13H14O2S): C, 66.64; H, 6.02; S, 13.68. Found: C, 66.55; H, 6.11;
S, 13.58.
3.12. 2-Hydroxy-3-(o-tolylthio)-4H-chromen-4-one (Table 2, entry
11)
3.8. 3-Hydroxy-2-(o-tolylthio)cyclohex-2-en-1-one (Table 2, entry
7)
dH (400 MHz, DMSO‑d6) 2.54 (s, 3H, CH3), 7.23e7.28 (m, 4H, Ar),
7.48e7.52 (m, 1H, Ar), 7.62 (d, 2H, J ¼ 7.6 Hz, Ar), 7.86e7.89 (m, 1H,
Ar). dC (100 MHz, DMSO‑d6) 21.2, 102.2, 115.9, 119.8, 120.7, 123.3,
123.4, 124.2, 126.1, 131.1, 132.9, 138.2, 153.0, 163.8, 168.0, 179.3. Anal.
Calcd for (C16H12O3S): C, 67.59; H, 4.25; S, 11.28. Found: C, 67.70; H,
4.17; S, 11.18.
dH (400 MHz, DMSO‑d6) 1.94e2.00 (m, 2H, CH2), 2.30 (s, 3H,
CH3), 2.57 (t, 4H, J ¼ 5.8 Hz, CH2), 6.73 (d, 1H, J ¼ 7.6 Hz, Ar), 6.97 (t,
1H, J ¼ 7.2 Hz, Ar), 7.03 (t, 1H, J ¼ 7.4 Hz, Ar), 7.12 (d, 1H, J ¼ 6.8 Hz,
Ar), 11.57 (s, 1H, OH). dC (100 MHz, DMSO‑d6) 19.3, 19.8, 28.9, 31.1,
Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
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8
N. Golzar et al. / Tetrahedron xxx (2018) 1e9
3.13. 3-(4-Chlorophenylthio)-2-hydroxy-4H-chromen-4-one
(Table 2, entry 12)
Ar), 7.27e7.31 (m, 2H, Ar), 7.60 (t, 1H, J ¼ 7.8 Hz, Ar), 7.88 (d, 1H,
J ¼ 8.0 Hz, Ar). dC (100 MHz, DMSO‑d6) 116.1, 117.9, 118.0, 123.3,
124.5, 124.6, 125.4, 128.6, 132.6, 137.7, 153.2, 161.8, 170.4.
dH (400 MHz, DMSO‑d6) 7.11 (d, 2H, J ¼ 7.6 Hz, Ar), 7.26e7.31 (m,
4H, Ar), 7.59 (t, 1H, J ¼ 6.4 Hz, Ar), 7.92 (d, 1H, J ¼ 6.4 Hz, Ar). dC
(100 MHz, DMSO‑d6) 89.4, 116.6, 119.6, 123.6, 125.3, 127.5, 128.9,
129.1, 132.7, 138.5, 153.9, 162.9, 172.2.
3.21. 3-Hydroxy-2-(phenylthio)cyclohex-2-en-1-one (Table 3, entry
2)
dH (400 MHz, DMSO‑d6) 1.92e1.99 (m, 2H, CH2), 2.50e2.56 (m,
4H, CH2), 7.00e7.07 (m, 3H, Ar), 7.21 (t, 2H, J ¼ 7.6 Hz, Ar), 11.64 (s,
1H, OH). dC (100 MHz, DMSO‑d6) 20.3, 29.4, 35.6, 103.8, 124.5, 125.5,
128.9, 138.3, 180.1, 193.7.
3.14. 4-Hydroxy-6-methyl-3-(phenylthio)-2H-pyran-2-one
(Table 2, entry 13)
dH (400 MHz, DMSO‑d6) 2.24 (s, 3H, CH3), 6.18 (s, 1H, ¼CH), 6.99
(t, 3H, J ¼ 4.2 Hz, Ar), 7.08 (d, 2H, J ¼ 8.0 Hz, Ar), 12.31 (s, 1H, OH). dC
(100 MHz, DMSO‑d6) 20.9, 91.5, 100.4, 126.6, 129.9, 133.6, 134.9,
163.5, 164.5, 173.1.
3.22. 4-Hydroxy-6-methyl-3-(phenylthio)-2H-pyran-2-one
(Table 3, entry 3)
dH (400 MHz, DMSO‑d6) 2.16 (s, 3H, CH3), 6.10 (s, 1H, ¼CeH),
6.96e6.99 (m, 3H, Ar), 7.09 (t, 2H, J ¼ 7.6 Hz, Ar),12.22 (s,1H, OH). dC
(100 MHz, DMSO‑d6) 21.0, 91.6, 100.5, 126.7, 130.0, 133.7, 135.0,
163.6, 164.6, 173.2.
3.15. 4-Hydroxy-6-methyl-3-p-tolylsulfanyl-pyran-2-one (Table 2,
entry 14)
dH (400 MHz, CDCl3) 2.21 (s, 3H, CH3), 2.22 (s, 3H, CH3), 5.99 (s,
1H, ¼CeH), 7.00 (d, 2H, J ¼ 8.4 Hz, Ar), 7.13 (d, 2H, J ¼ 8.4 Hz, Ar),
7.74 (s, 1H, OH). dC (100 MHz, CDCl3) 20.3, 21.0, 94.5, 98.8, 128.5,
129.8, 130.0, 137.2, 162.9, 165.3, 170.9. Anal. Calcd for (C13H12O3S): C,
62.89; H, 4.87; S, 12.91. Found: C, 63.01; H, 4.75; S, 12.82.
3.23. 4-Hydroxy-6-methyl-3-p-tolylsulfanyl-pyran-2-one (Table 3,
entry 4)
dH (400 MHz, CDCl3) 2.22 (s, 3H, CH3), 2.23 (s, 3H, CH3), 6.00 (s,
1H, ¼CeH), 7.02 (d, 2H, J ¼ 8.4 Hz, Ar), 7.14 (d, 2H, J ¼ 8.4 Hz, Ar),
7.75 (s, 1H, OH). dC (100 MHz, CDCl3) 20.0, 20.7, 94.1, 98.5, 128.2,
129.5, 129.7, 136.9, 162.5, 164.9, 170.5.
3.16. 2-Hydroxy-3-(4-methoxyphenylthio)-6-methyl-4H-pyran-4-
one (Table 2, entry 15)
dH (400 MHz, CDCl3) 2.28 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 6.06 (s,
1H, ¼CH), 6.84 (d, 2H, J ¼ 8.4 Hz, Ar), 7.37 (d, 2H, J ¼ 8.4 Hz, Ar). dC
(100 MHz, CDCl3) 20.2, 55.3, 95.6, 98.8, 114.8, 123.8, 131.5, 158.1,
159.1, 159.4, 170.3. Anal. Calcd for (C13H12O4S): C, 59.08; H, 4.58; S,
12.13. Found: C, 59.19; H, 4.69; S, 12.00.
3.24. 4-Hydroxy-3-(p-tolylthio)-2H-chromen-2-one (Table 3, entry
5)
dH (400 MHz, DMSO‑d6) 2.49 (s, 3H, CH3), 7.08 (d, 2H, J ¼ 7.6 Hz,
Ar), 7.23e7.28 (m, 4H, Ar), 7.56 (t, 1H, J ¼ 7.8 Hz, Ar), 7.88 (d, 1H,
J ¼ 6.4 Hz, Ar). dC (100 MHz, DMSO‑d6) 20.8, 89.0, 116.2, 119.2, 123.2,
124.9, 127.1, 128.5, 130.1, 132.4, 138.1, 153.5, 162.5, 171.8.
3.17. 3-Methyl-1-phenyl-4-(phenylthio)-1H-pyrazol-5-ol (Table 2,
entry 16)
3.25. 3-Hydroxy-2-(p-tolylthio)cyclohex-2-en-1-one (Table 3, entry
6)
dH (400 MHz, DMSO‑d6) 2.13 (s, 3H, CH3), 7.09 (d, 2H, J ¼ 7.2 Hz,
Ar), 7.13 (t, 1H, J ¼ 7.4 Hz, Ar), 7.29 (t, 3H, J ¼ 7.6 Hz, Ar), 7.48 (t, 2H,
J ¼ 8.0 Hz, Ar), 7.75 (d, 2H, J ¼ 8.0 Hz, Ar), 12.22 (s, 1H, OH). dC
(100 MHz, DMSO‑d6) 12.8, 87.2, 121.3, 125.3, 125.4, 126.2, 127.9,
129.4, 129.5, 138.8, 156.7, 166.2.
dH (400 MHz, DMSO‑d6) 1.85e1.91 (m, 2H, CH2), 2.16 (s, 3H, CH3),
2.45e2.46 (m, 4H, CH2), 6.87 (d, 2H, J ¼ 8.4 Hz, Ar), 6.97 (d, 2H,
J ¼ 8.0 Hz, Ar), 11.47 (s, 1H, OH). dC (100 MHz, DMSO‑d6) 20.4, 20.9,
34.0, 34.1, 104.6, 126.1, 129.7, 133.9, 134.8, 185.7, 190.6.
3.18. 5-Methyl-2-phenyl-4-p-tolylsulfanyl-3,4-dihydro-2H-
pyrazol-3-ol (Table 2, entry 17)
3.26. 2-Hydroxy-3-(o-tolylthio)-4H-chromen-4-one (Table 3, entry
7)
dH (400 MHz, DMSO‑d6) 2.38 (s, 3H, CH3), 2.65 (s, 3H, CH3), 7.13
(d, 2H, J ¼ 7.6 Hz, Ar), 7.25 (d, 2H, J ¼ 7.6 Hz, Ar), 7.43 (t, 1H,
J ¼ 7.0 Hz, Ar), 7.62 (t, 2H, J ¼ 7.8 Hz, Ar), 7.88 (d, 2H, J ¼ 8.0 Hz, Ar),
12.30 (s, 1H, OH). dC (100 MHz, DMSO‑d6) 12.1, 22.7, 85.4, 120.8,
125.5, 125.6, 126.2, 128.7, 128.8, 129.2, 137.2, 151.0, 155.4.
dH (400 MHz, DMSO‑d6) 2.49 (s, 3H, CH3), 7.18e7.27 (m, 4H, Ar),
7.43e7.47 (m, 1H, Ar), 7.58 (d, 2H, J ¼ 6.4 Hz, Ar), 7.82e7.84 (m, 1H,
Ar). dC (100 MHz, DMSO‑d6) 21.1, 102.1, 115.9, 119.7, 120.6, 123.2,
123.4, 124.1, 126.0, 131.0, 132.8, 138.1, 152.9, 163.7, 167.9, 179.2.
3.19. 4-(4-Chlorophenylthio)-3-methyl-1-phenyl-1H-pyrazol-5-ol
(Table 2, entry 18)
3.27. 3-(4-Chlorophenylthio)-2-hydroxy-4H-chromen-4-one
(Table 3, entry 8)
dH (400 MHz, DMSO‑d6) 2.11 (s, 3H, CH3), 7.11 (d, 2H, J ¼ 8.4 Hz,
Ar), 7.31 (t, 1H, J ¼ 7.4 Hz, Ar), 7.35e7.39 (m, 2H, Ar), 7.48e7.52 (m,
2H, Ar), 7.75e7.77 (m, 2H, Ar), 12.26 (s, 1H, OH). dC (100 MHz,
DMSO‑d6) 12.8, 86.1, 126.3, 127.0, 129.4, 130.0, 130.3, 131.0, 132.3,
138.0, 151.7, 156.2.
dH (400 MHz, DMSO‑d6) 7.03 (d, 2H, J ¼ 7.6 Hz, Ar), 7.19e7.24 (m,
4H, Ar), 7.52 (t, 1H, J ¼ 7.6 Hz, Ar), 7.85 (d, 1H, J ¼ 6.4 Hz, Ar). dC
(100 MHz, DMSO‑d6) 89.3, 116.5, 119.6, 123.5, 125.3, 127.4, 128.8,
130.5, 132.7, 138.5, 153.9, 162.8, 172.1.
3.28. 2-Hydroxy-3-(4-methoxyphenylthio)-6-methyl-4H-pyran-4-
one (Table 3, entry 9)
3.20. 2-Hydroxy-3-phenylsulfanyl-chromen-4-one (Table 3, entry
1)
dH (400 MHz, CDCl3) 2.26 (s, 3H, CH3), 3.77 (s, 3H, OCH3), 6.04 (s,
1H, ¼CH), 6.82 (d, 2H, J ¼ 8.8 Hz, Ar), 7.34 (d, 2H, J ¼ 8.4 Hz, Ar). dC
dH (400 MHz, DMSO‑d6) 7.03e7.09 (m, 3H, Ar), 7.18e7.22 (m, 2H,
Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
benzenethiols: Preparation of
j.tet.2018.07.049
a-thioaryl-b-dicarbonyls and 4-thioaryl-5-pyrazolones, Tetrahedron (2018), https://doi.org/10.1016/

N. Golzar et al. / Tetrahedron xxx (2018) 1e9
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(100 MHz, CDCl3) 20.3, 55.4, 95.8, 98.9, 115.0, 123.9, 131.7, 159.5,
159.6, 159.7, 170.4.
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3.29. 5-Methyl-2-phenyl-4-p-tolylsulfanyl-3,4-dihydro-2H-
pyrazol-3-ol (Table 3, entry 10)
dH (400 MHz, DMSO‑d6) 1.90 (s, 3H, CH3), 3.15 (s, 3H, CH3), 7.16
(d, 2H, J ¼ 8.4 Hz, Ar), 7.36 (t, 1H, J ¼ 7.4 Hz, Ar), 7.41e7.43 (m, 2H,
Ar), 7.55 (t, 2H, J ¼ 8.0 Hz, Ar), 7.80e7.82 (m, 2H, Ar). dC (100 MHz,
DMSO‑d6) 12.4, 23.1, 85.7, 121.1, 125.9, 126.6, 129.0, 129.5, 129.9,
130.6, 137.6, 151.3, 155.7.
3.30. 4-(4-Chlorophenylthio)-3-methyl-1-phenyl-1H-pyrazol-5-ol
(Table 3, entry 11)
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dH (400 MHz, DMSO‑d6) 2.04 (s, 3H, CH3), 7.04 (d, 2H, J ¼ 8.8 Hz,
Ar), 7.24 (t, 1H, J ¼ 7.4 Hz, Ar), 7.29e7.31 (m, 2H, Ar), 7.43 (t, 2H,
J ¼ 8.0 Hz, Ar), 7.68e7.70 (m, 2H, Ar), 12.19 (s, 1H, OH). dC (100 MHz,
DMSO‑d6) 12.7, 86.0, 121.5, 126.2, 126.9, 129.3, 129.9, 130.2, 130.9,
137.9, 151.7, 156.1.
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(Table 3, entry 12)
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dH (400 MHz, CDCl3) 1.12 (s, 6H, CH3), 2.41 (s, 2H, CH2), 2.58 (s,
2H, CH2), 7.11e7.26 (m, 5H, Ar), 8.13 (s, 1H, OH). dC (100 MHz, CDCl3)
28.1, 28.3, 31.5, 42.1, 51.0, 106.1, 126.3, 127.4, 129.0, 134.7, 178.3,
194.0.
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en-1-one (Table 3, entry 13)
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49165e49169;
6 (2016)
dH (400 MHz, DMSO‑d6) 1.06 (s, 6H, CH3), 2.48 (s, 2H, CH2), 2.49
(s, 2H, CH2), 6.73e6.76 (dd,1H, J1 ¼8.0 Hz, J2 ¼ 1.6 Hz, Ar), 7.03e7.07
(m, 1H, Ar), 7.13e7.17 (m, 1H, Ar), 7.36 (t, 1H, J ¼ 6.8 Hz, Ar), 8.10 (s,
1H, OH). dC (100 MHz, DMSO‑d6) 28.0, 31.4, 34.4, 47.0, 50.8, 100.7,
125.4, 125.5, 127.3, 127.7, 129.3, 137.0, 173.8, 189.0.
5
(2015)
(2014)
4
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Acknowledgment
We thank the Persian Gulf University Research Council for
support of this study.
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(2015) 312e315;
Appendix A. Supplementary data
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Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2018.07.049.
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Please cite this article in press as: N. Golzar, et al., CuI-catalyzed thioarylation of active methylene compounds with in situ generated
benzenethiols: Preparation of
j.tet.2018.07.049
a-thioaryl-b-dicarbonyls and 4-thioaryl-5-pyrazolones, Tetrahedron (2018), https://doi.org/10.1016/