Barium aluminate nano-powders efficient catalyst for the synthesis of novel benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives

Article abstract of DOI:10.1080/10426507.2017.1295961

Uniform nanopowders of barium aluminate (BaAl₂O₄) can be synthesized by a facile solution reaction at room temperature using barium and aluminum salts and 2-aminoethanol as a precipitating agent. The asprepared sample showed a good reactivity in the synthesis of benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives. Comparatively the method is efficient and eco-friendly, and finally, a range of compounds with variable functionalities in excellent yield can be achieved.

Full text of DOI:10.1080/10426507.2017.1295961

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Barium Aluminate nano-powders efficient catalyst
for the synthesis of novel benzo[b]thiophene,
thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine
derivatives
Hossein Yarahmadi, Majid Ghashang, Saeid Jabbar zare & Alireza
Khodaivandi
To cite this article: Hossein Yarahmadi, Majid Ghashang, Saeid Jabbar zare & Alireza
Khodaivandi (2017): Barium Aluminate nano-powders efficient catalyst for the synthesis of novel
benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives, Phosphorus, Sulfur,
and Silicon and the Related Elements, DOI: 10.1080/10426507.2017.1295961
To link to this article: http://dx.doi.org/10.1080/10426507.2017.1295961
Accepted author version posted online: 21
Feb 2017.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gpss20
Download by: [BYU Brigham Young University]
Date: 21 February 2017, At: 22:57

ACCEPTED MANUSCRIPT
Barium Aluminate nano-powders efficient catalyst for the synthesis of novel
benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives
Hossein Yarahmadi,1* Majid Ghashang,2 Saeid Jabbar zare 3 and Alireza Khodaivandi3
1Department of Chemical Engineering, Sirjan University of Technology, Sirjan, Iran. E-mail:
hy80iran@gmail.com
2Department of Chemistry, Faculty of Sciences, Najafabad Branch, Islamic Azad University,
P.O. Box: 517, Najafabad, Iran
3Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch,
Islamic Azad University, Najafabad, Iran
Abstract:
Uniform nanopowders of barium aluminate (BaAl2O4) can be synthesized by a facile solution
reaction at room temperature using barium and aluminum salts and 2-aminoethanol as a
precipitating agent. The as-prepared sample showed a good reactivity in the synthesis of
benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives. Comparatively
the method is efficient and eco-friendly, and finally, a range of compounds with variable
functionalities in excellent yield can be achieved.
O
O
X
NH2
S
O
ArHN
BaAl2O4 nano-powders
H2O/EtOH /reflux
+
ArHN
+ S
CN
8
X = CH2; S; NCH3
X
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Keywords:
BaAl2O4; benzo[b]thiophene; thieno[2,3-c]thiopyran; thieno[2,3-c]pyridine; Gewald reaction
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Introduction
In synthetic organic chemistry, multicomponent reactions (MCRs) have gained considerable
popularity in recent years due to their flexible, convergent, and atom-efficient nature. MCRs are
the basic reaction for the preparation of different heterocyclic compounds which are among of
the most interesting compounds in medicinal chemistry. In this context, the development of
multicomponent reactions is of prime importance, especially in the field of organic synthesis and
medicinal chemistry [1-12].
Substituted 2-aminothiophenes are important intermediates in organic synthesis, which have
been employed as building blocks to synthesize natural products, dyes, agrochemicals, and
conductivity-based sensors. Therefore, the synthesis of 2-aminothiophenes has recently attracted
considerable attention. Among all the reported methods, the Gewald reaction has gained
significant attention [13-17]. Many organic bases, such as morpholine and pyridine, were proved
to be viable catalysts for this reaction [18-25]. Highly reactive homogeneous bases catalysts are
efficient for this process, but they suffer from serious contamination and corrosion problems that
make essential the implementation of good separation and purification steps [23]. Recently, a
green approach to Gewald reaction has stimulated the application of sustainable solid base
catalysts as replacements for such liquid base catalysts so that the use of harmful substances and
generation of toxic wastes are avoided [18-25].
BaAl2O4 is a significant commercial inorganic chemical owing to its applicable versatility.
Barium aluminate has seldom been applied as an efficient catalyst for organic reactions [26-27].
Because of its mild basicity, eco-friendly, low cost and availability; more applied examples of
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
BaAl2O4 as a base catalyst are expected in the future [26-29]. The use of unconventional green
solvents in organic reactions has improved not only the aspect of the reactions from the
viewpoint of green and sustainable properties, but also the synthetic efficiency by stabilizing the
catalyst, changing the reaction selectivity or facilitating product isolation [28]. In continuation of
our research to explore eco-efficient transformations under environmentally benign conditions
such as the use of a green solvent and driven by the unique properties of BaAl2O4 nanoparticles
and the interest in the preparation and use of solid catalysts, herein, in this study, we
investigated, for the first time, BaAl2O4 nanoparticles as an efficient and green catalyst to
produce the title thiophene derivatives through the Gewald reaction in a multicomponent
condensation between a ketone, elemental sulfur and cyano acetamide derivatives in ethanol as a
green solvent under mild conditions (Scheme 1).
Results and discussion
BaAl2O4 nanopowder was prepared by a co-precipitation method using Al(NO3)3 and BaCl2
precursors with ethanolamine as a precipitant in an aqueous solution at room temperature
followed by calcination at 700°C.
The crystalline phase of BaAl2O4 sample was characterized using powder X-ray diffraction
(XRD) analysis (Figure 1). The XRD pattern showed that the sample possesses a hexagonal
structure characteristic for BaAl2O4 phase (space group P6322, Reference code: 00-017-0306).
The peaks characteristic of hexagonal phase of BaAl2O4 are revealed at 19.6, 22.1, 28.3, 34.3,
39.8, 40.1, 45.0, and 57.8 [2θ°]. The average particle size of BaAl2O4 nanopowder was
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
calculated suing the values of full width at half maximum (FWHM) of the most intensive XRD
diffraction peaks. The crystallite size obtained from Debye−Scherrer equation was 59 nm.
Figure 2 shows FE-SEM image of BaAl2O4 nanopowder. The surface of the sample is relatively
homogeneous with fine particles that are agglomerated together. The surface of nanopowder has
some fine pores which are attributed to a lot of gasses released during the combustion process.
The BaAl2O4 nanopowder is further characterized with energy dispersive X-ray spectroscopy
(EDS). The sample consists of Ba, O and Al elements as shown in Figure 3.
TEM image corroborates that there is a few aggregation of BaAl2O4 nanopowder and shows a
variable size of about 40--70 nm size with a non-uniformed distribution (Figure 4).
The particle size distribution of BaAl2O4 nanopowder is shown in Figure 5. The particle size
distribution ranging from 35-90 nm. The mean diameter of nanopowder about 58 nm.
Catalytic activity
The catalytic activity of BaAl2O4 nanopowder was examined on the synthesis of
benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine derivatives through Gewald
reaction.
As a preliminary test, we investigated the conversion of a mixture of cyclohexanone (1.0 mmol),
2-cyano-N-phenylacetamide (1.0 mmol), and elemental sulfur (1.0 mmol) in various solvents (5
mL) under reflux condition in the presence of BaAl2O4 (0.05 g) for 10-20 h (Table 1). As shown
in Table 1, the formation of 2-amino-N-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxamide as a targeted product was did not occur in non-polar solvents, in the absence of any
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
catalyst as well as at room temperature. While polar solvents showed good yields, protic solvents
such as ethanol and methanol were found to be the most efficient media for this transformation,
giving the highest yield of product. Also, the yield increased from 70% to 90% when the time of
the reaction was extended to 15h. Next, the effect of the different amount of the catalyst from
0.025 to 0.25 g on the productivity of the reaction was investigated. While the higher quantities
of the catalyst did not effectively improve the yield, optimization finally arrived at 0.025 g (89%
yield) when only a small variation in the yield was observed after increasing the amount of
catalyst.
With the optimized conditions in hand, we investigated reactions with different ketones and 2-
cyano-N-arylacetamide. In general, the desired products were obtained in high yields (Scheme 1,
Table 2). The results showed that ketone play a major role on the reaction rates. 1-
methylpiperidin-4-one reacted faster than cyclohexanone, while tetrahydrothiopyran-4-one
yielded the product over longer reaction times. The reaction with different 2-cyano-N-
arylacetamides leads to the formation of related products in high yield.
Experimental
All reagents were purchased from Merck and Aldrich and used without further purification. Field
Emission Scanning Electron Microscope (FE-SEM) images were obtained on HITACHI S-4160.
Dynamic light scattering (DLS) measurement was done using a Malvern Zetasizer Nano ZS
(ZEN 3600) instrument. The Transmission Electron Microscopy (TEM) of the sample was
performed on Philips EM208 transmission electron microscope with an accelerating voltage of
200 kV. The NMR spectra were recorded on a Bruker Avance DPX 400 MHz instrument. The
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
spectra were measured in DMSO-d6 relative to TMS (0.00 ppm). Melting points were
determined in open capillaries with a BUCHI 510 melting point apparatus. TLC was performed
1
on silica gel Polygram SIL G/UV 254 plates. The Supplemental Materials contains sample H
and 13C NMR spectra of the products 1-12 (Figures S 1 -- S 24)
Preparation of Barium Aluminate nanopowder
BaCl2 (20 mmol) and Al(NO3)3 (20 mmol) were dissolved in water (200 mL) (solution A). Then
2-aminoethanol (120 mmol) was dissolved in water (100 mL) (solution B). Solution (B) was
added dropwise to the solution (A) under vigorous magnetic stirring. The mixture was
continuously stirred for 60 min. The resulting precipitate was filtered and washed with water
(500 mL) and dried at 100°C for 5 h and finally calcined at 700°C for 2h.
Typical procedure:
A mixture of tetrahydrothiopyran-4-one (1 mmol), 2-cyano-N-phenylacetamide (1 mmol), sulfur
powder (1.5 mmol) and barium aluminate nanopowder (0.025 g) in EtOH (90% v/v) was
refluxed (80°C) for the appropriate time. The progress of the reaction was monitored by TLC
(Table 1). After completion of the reaction, the reaction mixture was dissolved in hot ethanol.
Simple filtration removed the catalyst. The solvent was concentrated, and recrystallization
purified the crude products from EtOH.
The characterization data of all compounds (Table 2, entries 1-12) are available in the
Supplemental Materials.
Conclusion
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
In summary, a general BaAl2O4 nanopowder catalyzed Gewald reaction was developed. The
products were achieved in high yields. The established system is not only efficient for the
synthesis of target compounds but also endowed with many salient features of nano-particle
Barium aluminate, such as cost-effective, high recyclable, reusable catalyst, environmental
benign solvent system and easy isolation of the product.
Acknowledgments
The financial support by the Sirjan University of Technology and the Najafabad Branch of
Islamic Azad University is gratefully acknowledged.
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
References
[1] (a) Cioc, R.C.; Ruijter, E.; Orru, R.V.A. Green Chem., 2014, 16, 2958-2975; (b)
Shaterian, H.R.; Yarahmadi, H.; Ghashang, M. Tetrahedron, 2008, 64, 1263-1269.
[2] Shafiee, M.M.R.; Ghashang, M.; Fazlinia, A. Curr. Nanosci. 2013, 9, 197-201.
[3] (a) Ghashang, M. Curr. Org. Synth. 2012, 9, 727-732; (b) Liu, C.; Zhou, L.; Jiang, D.;
Gu, Y. Asian. J. Org. Chem. 2016, 5, 367-372.
[4] Taghrir, H.; Ghashang, M.; Biregan, M.N. Chin. Chem. Lett. 2016, 27, 119-126.
[5] Ghashang, M.; Kargar, M.; Shafiee, M.R.M.; Mansoor, S.S.; Fazlinia, A.; Esfandiari, H.
Recent Pat. Nanotech. 2016, 9, 204-211.
[6] Shaterian, H.R.; Yarahmadi, H. Tetrahedron Lett. 2008, 49, 1297-1300.
[7] Ghashang, M.; Mansoor, S.S.; Aswin, K. Chin. J. Catal. 2014, 35, 127-133.
[8] Baziar, A.; Ghashang, M. React. Kinet. Mechan. Catal. 2016, 118, 463-479.
[9] Yarahmadi, H.; Shaterian, H.R. J. Chem. Res. 2012, 36, 52-55.
[10] Dehbashi, M.; Aliahmad, M.; Shafiee, M.M.R.; Ghashang, M. Nano-Metal Chem.
2013, 43, 1301-1306.
[11] Ghashang, M. Lett. Org. Chem. 2012, 9, 497-502.
[12] Shafiee, M.R.M.; Mansoor, S.S.; Ghashang, M.; Fazlinia, A. C. R. Chim. 2014, 17,
131-134.
[13] Puterová, Z.; Krutošíková, A.; Végh. D.D. Arkivoc, 2010, 1, 209-246.
[14] Gewald, K.; Schinke, E.; Bottcher, H. Chem. Ber. 1966, 99, 94-100.
[15] Mayer, R.; Gewald, K. Angew. Chem., Int. Ed. Engl. 1967, 6, 294-306.
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
[16] (a) Barnes, D.M.; Haight, A.R.; Hameury, T.; McLaughlin, M.A.; Mei, J.; Tedrow, J.S.;
Dalla, R.T. Tetrahedron, 2006, 62, 11311-11319; (b) Bai, R.; Liu, P.; Yang, J.; Liu, Ch.;
Gu, Y. ACS Sustainable Chem. Eng. 2015, 3, 1292-1297.
[17] Wang, K.; Kim, D.; Domling, A. J. Comb. Chem. 2010, 12, 111-118.
[18] Abaee, M.S.; Cheraghi, S. J. Sulfur Chem. 2014, 35, 261-269.
[19] Liang, C.; Lei, D.; Wang, X.; Zhang, Q.; Yao, Q. J. Sulfur Chem. 2013, 34, 458-463.
[20] Javadi, F.; Tayebee, R. Micropor. Mesopor. Mat. 2016, 231, 100-109.
[21] Zhao, D.D.; Li, L.; Xu, F.; Wu, Q.; Lin, X.F.; J. Mole. Catal. B: Enzym. 2013, 95, 29-
35.
[22] Tayebee, R.; Javadi, F.; Argi, G. J. Mole. Catal. A: Chem. 2013, 368, 16-23.
[23] Gouda, M.A.; Berghot, M.A.; Abd El-Ghani, G.E.; Elattar, K.M.; Khalil, A.E.M. Turk.
J. Chem. 2011, 35, 815-837.
[24] Huang, W.; Li, J.; Tang, J.; Liu, H.; Shen, J.; Jiang, H. Synth. Commun. 2005, 35, 1351-
1357.
[25] Nikolakopoulos, G.; Figler, H.; Linden, J.; Scammells, P.J. Bioorg. Med. Chem. 2006,
14, 2358-2365.
[26] Momayezan, M.; Ghashang, M.; Hassanzadeh-Tabrizi, S.A. Bulg. Chem. Commun.,
2015, 47, 809-815.
[27] Kazemi, N.; Ghashang, M.; Hassanzadeh-Tabrizi, S.A. Nanosci. Nanotechnol. Asia
2014, 4, 88-93.
[28] Casapu, M.; Grunwaldt, J.D.; Maciejewski, M.; Wittrock, M.; Göbel, U.; Baiker, A.
Appl. Catal. B: Environment., 2006, 63, 232-242.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
[29] Hodjati, S.; Bernhardt, P.; Petit, C.; Pitchon, V. Appl. Catal. B: Environment., 1998, 19,
209-219.
[30] Gu, Y. Green Chem., 2012, 14, 2091-2128.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Counts
1.sd
100
50
0
20
30
40
50
60
70
80
Position [°2Theta]
Figure 1: XRD pattern of nano-BaAl2O4 calcined at 700°C.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 2: FE-SEM photograph of BaAl2O4 nanopowder calcined at 700°C.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
cps/eV
25
20
15
Cl
O
Ba Al Cl
Ba
10
5
0
5
10
15
keV
20
25
30
Figure 3: EDS analysis of BaAl2O4 nanopowder
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 4: TEM image of BaAl2O4 nanopowder
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 5: Particle size distribution of BaAl2O4 nanopowder determined by DLS analysis
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
O
O
NH2
S
O
ArHN
BaAl2O4 nano-powders
H2O/EtOH /reflux
X = CH2; S; NCH3
+
ArHN
+ S
CN
8
X
X
Scheme 1: Preparation of benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine
derivatives using BaAl2O4 nanopowders
17
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 1: optimization of the reaction condition in the synthesis of 2-amino-4,5,6,7-tetrahydro-N-
phenylbenzo[b]thiophene-3-carboxamide
Entry
1
Catalyst (g)
0.05
T (°C) Solvent (5 mL) Time (h)
Yield (%)a
-
Reflux n-Hexane
Reflux CH2Cl2
Reflux Et2O
10
10
10
10
10
10
15
20
10
10
15
5
2
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
-
-
3
-
4
Reflux EtOAc
Reflux EtOH
Reflux MeOH
Reflux EtOH
Reflux EtOH
20
70
70
90
89
-
5
6
7
8
9
r.t.
r.t.
-
10
11
12
13
14
EtOH
-
0.025
0.075
0.1
Reflux EtOH
Reflux EtOH
Reflux EtOH
Reflux EtOH
89
85
74
71
5
0.25
10
a Isolated Yields;
18
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 2. Synthesis of benzo[b]thiophene, thieno[2,3-c]thiopyran and thieno[2,3-c]pyridine
derivatives
Entry
1
X
Ar-
Time (h)
15
Yield (%)
89
M.p. [Lit.
M.p.]Ref. (°C)
142-144
-CH2
****
[138-140]24
132-134
2
3
4
-S-
-N-CH3
-CH2
****
****
****
18
14
15
94
85
93
143-145
137-139
[131-134]34
140-142
5
6
-S-
-N-CH3
****
****
19
15
87
86
154-156
7
8
9
10
11
12
-CH2
-S-
-N-CH3
-CH2
-S-
****
****
****
****
****
****
14
16
14
17
20
16
79
89
84
83
80
79
153-155[-]25
162-164
154-156
161-163[-]25
165-167
-N-CH3
178-180
aAll of the reactions were conducted in the presence of nano-BaAl2O4 at reflux under optimized
conditions
19
ACCEPTED MANUSCRIPT