Synthesis of Thiazoles Catalyzed by Dichlorotriazine Attached to Graphene Oxide

Full text of DOI:10.1080/00304948.2021.1920788

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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Synthesis of Thiazoles Catalyzed by
Dichlorotriazine Attached to Graphene Oxide
Hossein Shahbazi-Alavi, Ali Kareem Abbas & Javad Safaei-Ghomi
To cite this article: Hossein Shahbazi-Alavi, Ali Kareem Abbas & Javad Safaei-Ghomi (2021)
Synthesis of Thiazoles Catalyzed by Dichlorotriazine Attached to Graphene Oxide, Organic
Preparations and Procedures International, 53:4, 426-430, DOI: 10.1080/00304948.2021.1920788
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
2021, VOL. 53, NO. 4, 426–430
https://doi.org/10.1080/00304948.2021.1920788
OPPI BRIEF
Synthesis of Thiazoles Catalyzed by Dichlorotriazine
Attached to Graphene Oxide
Hossein Shahbazi-Alavia, Ali Kareem Abbasb, and Javad Safaei-Ghomic
b
aYoung Researchers and Elite Club, Kashan Branch, Islamic Azad University, Kashan, Iran; College of
c
Applied Medical Sciences, University of Kerbala, Kerbala, Iraq; Department of Organic Chemistry,
Faculty of Chemistry, University of Kashan, Kashan, Iran
ARTICLE HISTORY Received 29 January 2020; Accepted 27 November 2020
Among their valuable activities, 1,3-thiazoles show anticancer,1 antimicrobial,2 anti-
inflammatory,3 and anti-Candida properties.4 These properties make 1,3-thiazoles appeal-
ing goals in organic synthesis. Past reports on the synthesis of 1,3-thiazole derivatives have
mentioned such catalysts as DBU,5 HClO4-SiO2,6 Bi(SCH2COOH)3,7 [Et3NH][HSO4],8
and ytterbium(III) triflate.9 Each of these procedures may have its own advantages but
also suffer from such apparent drawbacks as prolonged reaction times, complicated work-
up, low yield, or hazardous reaction conditions. Recently, graphene oxide (GO) has
attracted significant interest as a catalyst in organic synthesis.10–11 Graphene and GO have
large specific surface areas, chemical stability and high surface-to-volume ratios.12–13 GO
is an efficient platform for functionalized graphene platelets that can potentially confer
mechanical, thermal and electronic properties. Both small molecules and polymers have
been covalently attached to GO’s highly reactive oxygen functionalities, or non-covalently
attached on the graphene surfaces, for potential utilization in polymer composites, sensors,
paper-like materials, drug-delivery systems and photovoltaic applications.14–18 We have
previously reported the use of crosslinked sulfonated polyacrylamide tethered to nano-
Fe3O4 as a catalyst for the synthesis of 1,3-thiazoles.19 As a companion study, we now
report an easy method for the synthesis of these compounds through a three-component
reaction of carbon disulfide, phenacyl bromide or 4-methoxyphenacyl bromide and a pri-
mary amine, using graphene oxide dichlorotriazine (GO-DCT) as an efficient catalyst. The
reaction is conducted under reflux in ethanol (Scheme 1).
The process for the preparation of graphene oxide dichlorotriazine (GO-DCT) cata-
lyst is shown in Scheme 2. Graphene oxide nanosheets (GO) were prepared by modified
Hummer’s method,17 and subsequently functionalized with dichlorotriazine (see
Experimental section).
We used the reaction of carbon disulfide, phenacyl bromide and benzyl amine on
1 mmol scale as a model reaction and carried it out in the presence of CAN, NaHSO4,
NiCl2, ZrOCl2, p-TSA, CuI and GO-DCT. We found that the reaction gave useful
results in the presence of GO-DCT (2 mg) under reflux conditions (Table 1). The best
results were exemplified in Entry 12, with 92% yield. Further to this, we also reacted
CONTACT Hossein Shahbazi-Alavi
hossien_shahbazi@yahoo.com
Young Researchers and Elite Club, Kashan
Branch, Islamic Azad University, Kashan, Iran
Supplemental data for this article can be accessed online at https://doi.org/10.1080/00304948.2021.1920788.
ß 2021 Taylor & Francis Group, LLC

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
427
Scheme 1. Synthesis of thiazoles using GO-DCT.
Scheme 2. Preparation route for graphene oxide-dichloro triazine (GO-DCT).
Table 1. Optimization of reaction conditions using different catalysts.a
Entry
Solvent (reflux)
Catalyst
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
—
500
250
300
250
200
250
200
200
200
200
200
200
200
39
53
45
58
64
62
70
73
78
85
88
92
92
CAN (7 mol %)
NaHSO4 (5 mol %)
NiCl2 (5 mol%)
ZrOCl2 (4 mol%)
p-TSA (4 mol%)
CuI (8 mg)
GO-DCT (2 mg)
GO-DCT (2 mg)
GO-DCT (2 mg)
GO-DCT (1 mg)
GO-DCT (2 mg)
GO-DCT (3 mg)
9
DMF
10
11
12
13
CH3CN
EtOH
EtOH
EtOH
aPhenacyl bromide (1 mmol), carbon disulfide (1 mmol) and benzyl amine (1 mmol).
bIsolated yield.
phenacyl bromide or 4-methoxyphenacyl bromide with carbon disulfide and other pri-
mary amines and found uniformly good results (Table 2, mean 83%). The yield did not
appear to be particularly sensitive to the substituent groups. The structures of the prod-
1
ucts were deduced from their H NMR, 13C NMR, FT-IR, and elemental analyses. To
put the present results into context with our previous report on crosslinked sulfonated
polyacrylamide tethered to nano-Fe3O4, we found that the GO-DCT catalyst was some-
what easier to prepare once the graphene oxide was on hand. The yields using GO-
DCT were only marginally lower and the reaction times were only slightly longer.
Either catalyst was thus amply suited to the preparation of the 1,3-thiazoles.
The reusability of GO-DCT was studied for the model reaction, and it was found
that product yields lessened only to a very small extent on each reuse (run 1, 92%; run
2, 92%; run 3, 91%; run 4, 91%; run 5, 90%; run 6, 90%). After completion of the

428
H. SHAHBAZI-ALAVI ET AL.
Table 2. Synthesis of thiazoles 4 using GO-DCT.
Product
R
Ar
Time
Yielda
4a
4b
4c
4d
4e
4f
4g
4h
4i
PhCH2
Ph
Ph
Ph
Ph
Ph
Ph
4-OMe-Ph
4-OMe-Ph
4-OMe-Ph
4-OMe-Ph
200 min
210 min
220 min
200 min
205 min
180 min
210 min
220 min
230 min
200 min
92%
84%
82%
82%
86%
90%
86%
80%
78%
84%
3,4-Cl2PhCH2
PhC4H3CH2
furanyl-CH2
4-FPhCH2
2-OMe-PhCH2
4-Me-PhCH2
PhCH2
furanyl-CH2
2-OMe-PhCH2
4j
aIsolated yield.
reaction (as determined by TLC), CHCl3 was added. The GO-DCT was insoluble in
CHCl3 and it could therefore be obtained by simple filtration. The catalyst was washed
four times with ethanol and dried at room temperature for 15 h prior to re-use.
In conclusion, our procedure uses GO-DCT under reflux in ethanol for the synthesis
of 4-phenyl-1,3-thiazole-thiones. The advantages of this method include its simplicity,
the reusability of the catalyst, low catalyst loading, and easy separation of products, with
no recrystallization required.
Experimental section
1H NMR and 13C NMR spectra were recorded on a Bruker Avance-400 MHz spectrom-
eter using CDCl3 as solvent. The progress of the reactions was monitored by thin-layer
chromatography (TLC) on Riedel-de Haen plates coated with silica gel 60 F254, using
n-hexane/ethyl acetate 8:2 as the mobile phase. The elemental analyses (C, H, N) were
obtained on a Carlo ERBA Model EA 1108 analyzer. Fourier transform infrared (FT-IR)
spectra were recorded on a WQF-510 spectrometer. The mass spectra were recorded on
a Joel D-30 instrument at an ionization potential of 70 eV. The energy-dispersive X-ray
spectroscopy (EDS) measurements were performed on an SAMX analyzer. Powder X-
ray diffraction (XRD) measurements were carried out on a Philips diffractometer of the
X’pert Company. The characteristic peaks in the spectrum are in agreement with the
standard XRD pattern of functionalized-graphene oxides. SEM images were taken on a
MIRA3- TESCAN. Our SEM images of graphene oxide dichlorotriazine nanoplatelets
show crumpled thin layers with wrinkles and folds on the surface of GO. The AFM
images of GO and graphene oxide dichlorotriazine easily confirm the wrinkled two-
dimensional characteristic of the GO nanosheets. Energy Dispersive Spectroscopy (EDS)
confirmed the presence of carbon, oxygen, nitrogen and chlorine. XRD, SEM, EDS, FT-
IR, and AFM data were submitted for review and are available from the corresponding
author upon request.
Preparation of graphene oxide dichlorotriazine (GO-DCT)
GO was prepared from graphite powder according to Hummer’s procedure.17 Graphite
powder (500 mg) was dispersed into 200 mL H2SO4 (98%); this was sonicated for 2 h at
50ꢀ C and stirred for 24 h. Afterward, 10 g NaNO3 was added into the stable dispersion

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
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and the mixture was placed in an ice-water bath under stirring for 1 h. Then 30 g
KMnO4 was added slowly and was stirred for 24 h. Next 200 mL H2O and 60 mL H2O2
was added into the mixture. The color of the reaction was light brown. The solid was
filtered and washed with water and dried in an oven at 60 ꢀC for 8 hours. The obtained
GO (1 g) was dispersed in 10 mL CHCl3, then 500 mg of 2,4,6-trichloro-1,3,5-triazine
was added and stirred for 24 h at room temperature. The obtained solid was filtered,
rinsed with CHCl3 and dried in an oven at 50 ꢀC for 4 hours.
General procedure for the synthesis of 1,3-thiazoles
A mixture of primary amine (1.0 mmol) and carbon disulfide (1.0 mmol) in ethanol
(8 mL) was stirred for 5 min and then phenacyl bromide or 4-methoxyphenacyl bromide
(1.0 mmol) and GO-DCT (2 mg) were added, and the mixture was stirred for the appro-
priate times, as determined by TLC (n-hexane/ethyl acetate 8:2). After completion of
the reaction, CHCl3 was added. The catalyst was insoluble in CHCl3 and it could there-
fore be recycled by a simple filtration as described above. The solvent was evaporated
and the solid washed with EtOH to get pure product. All of the compounds were
1
known19 and were identified on the basis of their H NMR, 13C NMR, and FT-IR,
which were submitted for review.
Acknowledgment
The authors are grateful to the University of Kashan for supporting this work by Grant NO:
159196/XXI.
References
1. K. M. Dawood and S. M. Gomha, J. Heterocyclic Chem., 52, 1400 (2015). doi:10.1002/jhet.
2250
2. B. F. Abdel-Wahab, H. A. Abdel-Aziz, and E. M. Ahmed, Monatsh. Chem., 140, 601 (2009).
doi:10.1007/s00706-008-0099-x
3. R. N. Sharma, F. P. Xavier, K. K. Vasu, S. C. Chaturvedi, and S. S. Pancholi, J. Enzyme
Inhib. Med. Chem., 24, 890 (2009). doi:10.1080/14756360802519558
ꢀ
4. L. T. Maillard, S. Bertout, O. Quinonero, G. Akalin, G. Turan-Zitouni, P. Fulcrand, F.
Demirci, J. Martinez, and N. Masurier, Bioorganic Med. Chem. Lett., 23, 1803 (2013). doi:10.
1016/j.bmcl.2013.01.039
5. T. Masquelin and D. Obrecht, Tetrahedron, 57, 153 (2001). doi:10.1016/S0040-
4020(00)01003-6
6. D. Kumar, M. Sonawane, B. Pujala, V. K. Jain, and A. K. Chakraborti, Green Chem., 15,
2872 (2013). doi:10.1039/c3gc41218k
7. N. Foroughifar and S. Ebrahimi, Chin. Chem. Lett., 24, 383 (2013).
8. D. D. Subhedar, M. H. Shaikh, M. A. Arkile, A. Yeware, D. Sarkar and B. B. Shingate,
Bioorganic Med. Chem. Lett., 26, 1704 (2016). doi:10.1016/j.bmcl.2016.02.056
9. W. Su, C. Liu, and W. Shan, Synlett., 5, 725 (2008). doi:10.1055/s-2008-1032100
10. Y. Gao, P. Tang, H. Zhou, W. Zhang, H. Yang, N. Yan, G. Hu, D. Mei, J. Wang, and D. Ma,
Angew. Chem. Int. Ed., 55, 3124 (2016). doi:10.1002/anie.201510081
11. S. Khodabakhshi, F. Marahel, A. Rashidi, and M. K. Abbasabadi, J. Chin. Chem. Soc., 62, 389
(2015). doi:10.1002/jccs.201400349
12. L. Farzin and M. Amiri. J. Nanoanalysis, 5, 241 (2018).

430
H. SHAHBAZI-ALAVI ET AL.
13. F. Hosseini, H. Shirkhanloo, and N. M. Kazemi, J. Nanoanalysis, 4, 99 (2017).
14. N. Mohanty and V. Berry, Nano Let., 8, 4469 (2008). doi:10.1021/nl802412n
15. C. H. Lu, H. H. Yang, C. L. Zhu, X. Chen, and G. N. Chen, Angew. Chem., Int. Ed., 48, 4787
(2009).
16. S. Stankovich, R. Piner, S. T. Nguyen, and R. S. Ruoff, Carbon, 44, 3342 (2006). doi:10.1016/
j.carbon.2006.06.004
17. W. S. Hummers and R. E. Offeman, J. Am. Chem. Soc., 80, 1339 (1958). doi:10.1021/
ja01539a017
18. H. N. Tien, V. H. Luan, T. K. Lee, B. S. Kong, J. S. Chung, E. J. Kim, and S. H. Hur, Chem.
Eng. J., 211, 97 (2012). doi:10.1016/j.cej.2012.09.046
19. H. Shahbazi-Alavi, S. Khojasteh-Khosro, J. Safaei-Ghomi and M. Tavazo, BMC Chemistry,
13, 120 (2019).