Development of a synthesis of diphenylthiophenes via a one-pot reaction of phenylacetylene and sulfur

Article abstract of DOI:10.1080/104265090928040

The one-pot synthesis of a mixture of diphenylthiophenes 1 and 2 from the reaction of phenylacetylene and sulfur under various reaction conditions was studied. Potential intermediates and a reaction pathway are postulated. Copyright Taylor & Francis Inc.

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Phosphorus, Sulfur, and Silicon
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Development of a Synthesis
of Diphenylthiophenes
via a One-Pot Reaction of
Phenylacetylene and Sulfur
Hossein Reza Darabi a , Kioumars Aghapoor a &
Farshid Mohsenzadeh a
a Chemistry and Chemical Engineering Research
Center of Iran , Tehran, Iran
Published online: 16 Aug 2006.
To cite this article: Hossein Reza Darabi , Kioumars Aghapoor & Farshid Mohsenzadeh
(2005) Development of a Synthesis of Diphenylthiophenes via a One-Pot Reaction of
Phenylacetylene and Sulfur, Phosphorus, Sulfur, and Silicon and the Related Elements,
180:11, 2483-2489, DOI: 10.1080/104265090928040
To link to this article: http://dx.doi.org/10.1080/104265090928040
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Phosphorus, Sulfur, and Silicon, 180:2483–2489, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090928040
Development of a Synthesis of Diphenylthiophenes via a
One-Pot Reaction of Phenylacetylene and Sulfur
Hossein Reza Darabi
Kioumars Aghapoor
Farshid Mohsenzadeh
Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
The one-pot synthesis of a mixture of diphenylthiophenes 1 and 2 from the reaction of
phenylacetylene and sulfur under various reaction conditions was studied. Potential
intermediates and a reaction pathway are postulated.
Keywords Diphenylthiophenes; intermediates; phenylacetylene; reaction pathway;
sulfur
INTRODUCTION
Thiophenes, one of the most fundamental heterocycles, occur abun-
dantly as structural units in many natural and un-natural molecules.
Thiophenes have potential applications in the flavor and pharmaceu-
tical industries1 and in conducting polymer applications.2 They also
are important intermediates in organic synthesis3 and their synthetic
study continues to attract much attention.
Thiophenes, generally, have been prepared by the reaction of the cor-
responding 1, 4-diketones with phosphorus pentasulfide and hydrogen
sulfide,4 Lawesson’s reagent,5 or Steliou’s reagent.6 Symmetric thio-
phenes can be prepared7 from the condensation of β-chloroacroleins
with benzyl bromides in the presence of sodium sulfide. Another route
toward the synthesis of thiophenes is the one-pot reaction of phenyl-
acetylene with sulfur, which so far has attracted little attention. This
reaction has a rather bad reputation for not being useful for preparative
purposes due to the formation of isomeric mixtures of thiophenes with
poor yields. We present here the results of detailed investigations on
Received August 13, 2004; accepted November 25, 2004.
The authors thank Dr. M. Yalpani for fruitful discussions.
Address correspondence to Hossein Reza Darabi, Chemistry and Chemical Engineer-
ing Research Center of Iran, PO Box 14335-186, Tehran, Iran. E-mail: darabi@ccerci.ac.ir
2483

2484
H. R. Darabi et al.
this subject. During this study, we were interested in investigating the
possible intermediates of products to explain the contradictory results
which have been reported thus far.8 Finally, our current interest has led
us to develop a practical one-step preparation of thiophenes (Scheme 1).
SCHEME 1
RESULTS AND DISCUSSION
Based on the literature procedure, heating a solvent-free mixture of
phenylacetylene with sulfur gave 2, 4-diphenyl thiophene 1 in a 32%
yield. We repeated this reaction at 100–120◦C and obtained similar
results (Table I, Entries a, b). We observed that the two reactants formed
TABLE I Formation of Thiophenes 1 and 2 From the Reaction of
Phenylacetylene and Sulfur (1: 2)
Yield (%)
Entry Method Solvent
Temperature/◦C Time (min) Total (1 : 2)a Total (5: 4)
a
b
c
d
e
f
g
h
i
SBb
SB
—
—
100
120
120
120
160
160
185
180
180
—
60
120
240
240
60
180
300
120
180
5
45 (34: 11)
53 (33: 20)
2.5 (0.5: 2)
3 (1: 2)
63 (13: 50)
73 (10: 63)
98 (18: 80)
14 (5: 9)
17 (3: 14)
0.5 (0: 0.5)
1 (0: 1)
24 (0: 24)
11 (1: 10)
—
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
MW f
MW
Toluenec
EGd
EG
EG
EG
Decane
DCBe
Toluene
—
73 (46: 27) 14.5 (0: 14.5)
71 (38: 33)
18 (13: 5)
15 (4: 11)
16 (1: 15)
3 (0: 3)
4 (0: 4)
j
k
l
—
—
2
2.3
MW
—
62 (41: 21) 12.5 (1.5: 11)
m
n
o
p
MW
MW
MW
MW
—
—
—
EG
—
—
—
—
3.5
5
5
94 (55: 39)
94 (59: 35)
66 (34: 32)
84 (54: 30)
1.5 (0: 1.5)
2.9 (0.5: 2.4)
14 (0: 14)
3
8.5 (0: 8.5)
aIn the product mixture, 2–4% of thiophene 3 was also Presented.
bSB = Sand bath.
c
Phenylacetylene was recovered in 91%.
dEG = ethylene glycol.
eDCB = 1,4-dichlorobenzene.
f Under microwave heating (MW).

Development of a Synthesis of Diphenylthiophenes
2485
an opaque and homogenous phase at 95◦C with a color changing to
red. At this temperature, an exothermic reaction occurred, followed by
loss of hydrogen sulfide. It is interesting to mention that conversion of
sulfur to monoclinic sulfur occurred at 95◦C and, therefore, it seems
that there may be a relation between the temperature of the formation
of the homogenous phase of the reactants and the temperature of the
conversion of sulfur to monoclinic sulfur.
When we analyzed the crude reaction mixtures by GC-MS, we found
2, 5-diphenyl thiophene 2 and a trace amount of 3, 4-diphenyl thio-
phene 3 as new products of this reaction. This finding prompted us
to investigate both the reaction pathway and the optimization of the
reaction.
1
The identification of the products was generally performed by H
NMR and MS spectral analyses.
Solvent Effect
Table I shows selected experiments under various reaction conditions.
Contrary to our expectations, refluxing a mixture of phenylacetylene
and sulfur in toluene or heating it in ethylene glycol at 120◦C for 4 h
did not lead to the desired reaction and more than 95% of phenylacety-
lene was recovered (Table I, entries c, d). However, when the reaction
mixture in ethylene glycol was heated at 160◦C for 1 h, thiophenes 1
and 2 were formed followed by the loss of hydrogen sulfide (Table I,
entries e and f). The best result was achieved by heating a mixture of
phenylacetylene and sulfur at 185◦C for 5 h, which led to formation 2 in
an 80% yield (Table I, entry g). Surprisingly, the selective formation of
product 2 is clear, which is in contrary to a solvent-free condition. There-
fore, the best reaction conditions for obtaining the major amounts of 2
is described in the general procedures (see the Experimental Section)
using ethylene glycol as a solvent. According to this procedure, products
1 and 2 were formed in a ca. 1:4 ratio.
The reaction also was carried out in nonpolar, high boiling point sol-
vents such as decane and 1, 4-dichlorobenzene (DCB). The experimen-
tal results showed a decrease in the total yield of thiophenes. Moreover,
products 1 and 2 were formed in a ca. 2:1 ratio, showing a higher selec-
tivity for 1 (Table I, entries h and i).
The solvent-free reaction of phenylacetylene with sulfur under mi-
crowave heating also was studied. During the irradiation, when the
sulfur dissolved, an exothermic reaction took place, with the change of
color from yellow to red. The exothermic reaction occurred after 2.3 min
of irradiation. After this time, the yield of products suddenly increased
as shown in Table I and Scheme 2. The best reaction conditions for

2486
H. R. Darabi et al.
obtaining the major amounts of 1 is described in the general procedures
(see the Experimental Section) by 5 min irradiation under microwave
condition (Table I, entry n). According to this procedure, products 1 and
2 were formed in a ca. 2:1 ratio.
The addition of ethylene glycol as a polar solvent to the reaction
mixture resulted in the completion of the reaction in a shorter time
(3 min) and gave 1 and 2 in a 54% and 26% yield, respectively (2:1 ratio).
In this case, the color of the reaction mixture gradually changed, but
without any explosion. The effects of the various solid supports under
microwave irradiation also were studied, for which silica gel showed an
improved efficiency in the yield of products.
Reaction Pathway
As shown in Table I, this reaction affords small amounts of 1, 4-dithiins
4 and 5 in addition to the thiophenes 1–3, as indicated by GC-Mass
spectrometric analysis.As outlined in Scheme 2, it is known in the
literature10 that 1, 4-dithiin 5 can be prepared in two steps from the self-
condensation of α-mercaptoacetophenone under acid catalysis condition
in a 50% yield. This method is restricted to the formation of isomer 5.
Furthermore, thionation of diketosulfides, followed by the cyclodehy-
dration of the resulting monothiodiketone, led to selective preparation
of dithiin 4.10
SCHEME 2
As reported in the literature,11 1, 4-dithiins 5 and 4 undergo the
thermal extrusion of sulfur to afford the corresponding thiophenes 1 and
2, respectively. Under thermolysis condition, 1, 4-dithiin 4 can easily
be converted into the corresponding thiophene than that of 1, 4-dithiin
5. Therefore, as shown in Table I, a higher amount of 5 is detected to
confirm this result.

Development of a Synthesis of Diphenylthiophenes
2487
In accord with these facts, we propose the following sequence of steps
of the formation of products 1 and 2, as outlined in Scheme 3.
Further heating on the mixture of 1, 4-dithiins 5 and 4 leads to for-
mation of products 1 and 2. Therefore, predominant formation of thio-
phene 1 would result from this proposed path way:
SCHEME 3
CONCLUSION
In general, we have shown that phenylacetylene can be transformed
into thiophenes through the simple heating with sulfur in a one-pot
process in high yield. Surprisingly, unlike heating in a solvent-free con-
dition, the reaction in decane or ethylene glycol needs higher temper-
atures to complete the reaction. We found that selective formations of
products are strongly dependent on reaction media. In a polar medium,
thiophene 2 selectively is formed, while, in nonpolar media, the major
formation of 1 was observed.
In contrast to heating under solvent-free conditions, an improved
yield was obtained by heating briefly with microwave irradiation.
We believe this one-pot reaction method provides a simple and highly
efficienct process for the preparation of the substituted thiophenes.
EXPERIMENTAL SECTION
Caution: Experiments should be carried out in an efficient hood to avoid
exposure to noxious vapors of hydrogen sulfide.
Products 1–5 were identified by GC-MS spectral comparison with au-
thentic specimens. Column chromatography was performed on Merck

2488
H. R. Darabi et al.
silica gel (0.040–0.063 particle size). For GC-MS analysis, a Fision in-
struments gas chromatograph 8000 equipped to a mass detector (Trio
1000) with 70 ev was used. A 60 m x 0.25 mm column packed with
WCOT fused silica gel CP-sil 5 CB was employed. The carrier gas was
helium and the inlet pressure was 14 psi.
Reaction of Phenylacetylene and Sulfur
(a) Under Refluxing Condition
A mixture of phenylacetylene (1.0 mmol) and sulfur (2.2 mmol) in
ethylene glycol (30 mL) was heated in an oil bath at 185 ◦C for 5 h. The
dark red reaction mixtures were directly analyzed by GC-MS and/or
were subjected to column chromatography. The products 1 and 2 were
formed in a 98% yield (in a ca. 1:4 ratio). Careful chromatography on
the silica gel and by gradual elution with light petroleum ether-benzene
afforded products 1 and 2 in a 15% and 73% yield, respectively. Further
crystallization from ethanol gave pure products. The identification of
1
the isolated products generally was performed by H NMR and MS
spectral analyses.
(b) Under Pyrolysis Condition
A mixture of phenylacetylene (1 mmol) and sulfur (2.2 mmol) in an
open pyrex glass flask was heated in sand/oil bath for 120 minutes.
Based on a GC-MS analysis, 33% of 1 and 20% of 2 was obtained. After
2 h, the reaction was not completed and 20% of phenylacetylene also
was recovered.
(c) Under Microwave Condition
A mixture of phenylacetylene (1 mmol) and sulfur (2.2 mmol) in an
open Pyrex glass flask was exposed to microwave irradiation at 900 W
for 5 min with 30 s intervals.12
After 2.3 min irradiation, an explosive reaction was observed and
the color of the mixture changed from yellow to red. The crude products
were directly analyzed by GC-MS and afforded the total products 1
and 2 in a 94% yield in a ca. 2:1 ratio. A careful chromatography on
silica gel and by gradual elution with light petroleum ether-benzene
afforded products 1 and 2 in a 55% and 27% yield, respectively. Further
crystallization from ethanol gave pure products.
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1973).

Development of a Synthesis of Diphenylthiophenes
2489
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