One-Pot Synthesis of Polyhydroquinolines Catalyzed by ZnCl2 Supported on Nano Fe3O4@SiO2

Full text of DOI:10.1080/00304948.2019.1600132

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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One-Pot Synthesis of Polyhydroquinolines
Catalyzed by ZnCl Supported on Nano Fe O @SiO
2
2
3 4
Behrooz Maleki, Heshmatollah Alinezhad, Hengameh Atharifar, Reza
Tayebee & Akram Vedad Mofrad
To cite this article: Behrooz Maleki, Heshmatollah Alinezhad, Hengameh Atharifar, Reza Tayebee
Akram Vedad Mofrad (2019) One-Pot Synthesis of Polyhydroquinolines Catalyzed by ZnCl2
Supported on Nano Fe O @SiO , Organic Preparations and Procedures International, 51:3,
&
3
4
2
301-309, DOI: 10.1080/00304948.2019.1600132
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2019 Taylor & Francis Group, LLC
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ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2019.1600132
OPPI BRIEF
One-Pot Synthesis of Polyhydroquinolines
Catalyzed by ZnCl Supported on
2
Nano Fe O @SiO
3
4
2
1
2
Behrooz Maleki, Heshmatollah Alinezhad, Hengameh
1
1
1
Atharifar, Reza Tayebee, and Akram Vedad Mofrad
1
Department of Chemistry, Hakim Sabzevari University, Sabzevar, 96179-
7
6487, Iran
2
Faculty of Chemistry, University of Mazandaran, P.O. Box 47416-95447,
Babolsar, Iran
The development of an atom-economical approach for the efficient construction of
diversely functionalized molecules from easily accessible starting materials is always a
1
–3
special issue for synthetic organic chemists.
1,4-DHP) nucleus is a rich source of biological molecules which are useful as antihy-
pertensive, vasodilator, antitherosclerotic, antitumor, geroprotective and antidiabetic
The 4-substituted 1,4-dihydropyridine
(
4–8
agents.
These compounds also have activities as neuroprotectants and as platelet
anti-aggregants. They have cerebral antischaemic activity in the treatment of
9
Alzheimer’s disease and chemosensitizer behavior in tumor therapy. The valuable car-
diovascular agents nifepidin, felodipine and amlodipine belong to this category of com-
10
pounds, and they play important roles in hypertension treatments. They have shown
11–12
usefulness in the treatment of angina pectoris and other cardiovascular diseases.
The best methods for the synthesis of polyhydroquinolines are multicomponent
reactions. These advantageous reactions are in agreement with green chemistry princi-
13–17
ples such as atom economy and resource-effectiveness bond-forming efficiency.
There are many approaches in the literature for the preparation of polyhydroquino-
1
8
lines. They include the use of such catalysts as Co O -CNTs, Ni0.35Cu0.25Zn0.4Fe O
3
4
2
4
22
19
20
21
MNPs, ceric ammonium nitrate, cetyltrimethylammonium bromide, MCM-41,
23
24
25
26
p-TSA,
scolecite,
hafnium(IV)bis(perfluorooctanesulfonyl)imide,
PPA-SiO ,
2
27
28
29
30
31
TiO2 NPs, Al (SO ) , VDDAP, Fe O @chitosan, Fe O -SA-PPCA, SbCl3-
2
4 3
33
3
4
3 4
32
34
SiO2, MoO -SiO , 1,3-di-(bromo or chloro)-5,5-dimethylhydantoin and the poly-
3
2
3
5
meric catalyst [poly(AMPS-co-AA)].
In spite of the undeniable utility of the above methods, the majority have some lim-
itations including low yields, long reaction times, difficult preparations of the catalysts
or the use of hazardous solvents. In order to overcome these limitations and in
Received September 18, 2018; in final form January 7, 2019.
Address correspondence to Behrooz Maleki, Department of Chemistry, Hakim Sabzevari
University, Sabzevar, 96179-76487, Iran. E-mail: malekibehrooz@gmail.com
301

3
02
Maleki et al.
3 4 2 2
Scheme 1. Synthesis of polyhydroquinolines using Fe O @SiO /ZnCl as a catalyst under solv-
ent-free conditions.
36–46
continuation of our research on heterocyclic synthesis,
we became interested in
using a nanomagnetic catalyst for the synthesis of polyhydroquinolines.
Nanocatalysts are remarkably efficient due to their incomparable properties, such as
their large surface-to volume ratios, which dramatically increase their activity. This is con-
ducive to high selectivity and stability. The principal methods for their separation are centri-
fugation and filtration which do have some limitations, including most significantly the loss
4
7–48
of catalyst.
nanoparticles. These can be easily separated just by using an external magnet.
Because of its high surface area, excellent thermal and chemical stability and good
The best solution to overcome this particular limitation is to use magnetic
49–53
54–55
accessibility,
silica has an excellent record as a support. Recently, magnetic silica
nanoparticles have attracted great attention, because of their chemical inertness, excel-
lent thermal stability and lack of toxicity. This allows nanoparticles to be used in
56–67
organic reactions as catalysts or as supported catalysts.
In the present research, we were interested in using a nanocatalyst which would
incorporate ZnCl . The powerful Lewis acid properties of ZnCl make it useful for
2
2
68
organic reactions, and it has the advantages of low cost, nontoxicity and easy access.
Thus, in our work, ZnCl was immobilized on the surface of Fe O @SiO core–shell
2
3
4
2
69
nanoparticles
and was used in the synthesis of polyhydroquinoline derivatives
(Scheme 1). This nanocatalyst can be easy separated from the reaction mixture and so it
obeys one of the most important green chemistry principles, namely the recycling capability
of the catalyst.
In order to obtain the best conditions for this reaction, we optimized temperature,
solvent, and amount of catalyst and compared these to running the reaction in the
absence of catalyst. Our study started by using benzaldehyde (1 mmol), dimedone
(
1 mmol), ethyl acetoacetate (1.2 mmol), ammonium acetate (5 mmol) and Fe O @SiO /
3 4 2
ZnCl as catalyst. As shown in Table 1, the best result was achieved with 0.04 g of
2
ꢀ
catalyst under solvent-free conditions at 110 C (Table 1, entry 1). Then we did the reac-
tion with different amounts of catalyst and we found that 0.05 g is the optimum amount
(
Table 1, entry 7). We studied the reaction in the presence of Fe O and ZnCl separ-
3 4 2
ately, but the results were not satisfactory (Table 1, entries 8, 9). We did the reaction in
the absence of catalyst, and again the results were not acceptable (Table 1, entry 10).
ꢀ
Thus, we found that the best conditions for this reaction were 110 C and 0.05 g of
Fe O @SiO /ZnCl (entry 7).
3
4
2
2
In order to expand the scope of the reaction we used different aldehydes and studied the
effect of electron-donating and electron withdrawing substituent groups on the reaction. The
results are listed in Table 2. The average yield was 87%. Yields were uniformly high, and
the process does not appear to be especially sensitive to the electronic nature of the groups.
In order to determine the recyclability of this nanocatalyst, we used it in the model
reaction among benzaldehyde, ethyl acetoacetate, ammonium acetate and dimedone. After

Polyhydroquinolines
303
Table 1
Optimization of Reaction Conditions
a
Entry
Catalyst (g)
Conditions
Time (min) Yield (%)
ꢀ
ꢀ
ꢀ
1
2
3
4
5
6
7
8
9
Fe O @SiO /ZnCl (0.04 g) Solvent-free/110 C
25
25
25
25
25
25
25
60
25
60
88
82
89
74
70
81
90
34
72
28
3
4
2
2
Fe O @SiO /ZnCl (0.04 g) Solvent-free/100 C
3
4
2
2
Fe O @SiO /ZnCl (0.04 g) Solvent-free/120 C
3
4
2
2
Fe O @SiO /ZnCl (0.04 g)
Ethanol/reflux
Methanol/reflux
3
4
2
2
Fe O @SiO /ZnCl (0.04 g)
3
4
2
2
ꢀ
ꢀ
ꢀ
ꢀ
Fe O @SiO /ZnCl (0.03 g) Solvent-free/110 C
3
4
2
2
Fe O @SiO /ZnCl (0.05 g) Solvent-free/110 C
3
4
2
2
Fe O (0.04 g)
Solvent-free/110 C
Solvent-free/110 C
Solvent-free/110 C
3
4
ZnCl (0.04 g)
2
b
ꢀ
1
0
–
a
Isolated yield.
b
3 4 2 2
This reaction was carried out in the absence of Fe O @SiO /ZnCl .
completion of the reaction (as determined by TLC, see Experimental Section), we added
ml of hot ethanol, stirred for 2 minutes, the Fe O @SiO /ZnCl was separated using an
2
3
4
2
2
ꢀ
external magnet and then dried at 100 C for 2 h. It was then reused in the same reaction for
four successive runs in yields of 90%, 88%, 84% and 80% respectively.
In summary, we studied the synthesis of polyhydroquinoline derivatives using
Fe O @SiO /ZnCl as a nanocatalyst. This catalyst is excellent for this synthesis, giving
3
4
2
2
pure products in high yields and short reaction times. An important aspect is the recyc-
lability of this nanocatalyst, showing its economical and green qualities. We hope that
our work will stimulate further applications of this catalyst.
Experimental Section
All reagents were obtained from commercial sources. The measurements of melting
points were done on a Stuart BI Branstead Electrothermal IA9200 apparatus and were
uncorrected. A Shimadzu 435-U- 04 spectrophotometer (KBr) was used for recording
1
the FT-IR spectra. H NMR spectra were obtained using a Bruker 300 MHz spectrom-
eter, in DMSO-d or CDCl and using TMS as the internal reference. The catalyst was
6
3
69
prepared according to the method previously described.
Genaral Procedure for Synthesis of Polyhydroquinolines using ZnCl Supported on
2
Fe O @SiO Core–Shell Nanocatalyst
3
4
2
A mixture of aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1.2 mmol),
ammonium acetate (5 mmol) and Fe O @SiO /ZnCl (0.05 g) was prepared. The
3
4
2
2

3
04
Maleki et al.
Table 2
One-Pot Synthesis of Polyhydroquinolines using Fe O @SiO /ZnCl
3
4
2
2
0
mp ( C)
a
Entry
1
Product
Yield (%)
Time (min)
Found
Lit.
18
90
92
25
30
204-206
242-244
203-204
18
2
244-246
18
3
78
35
208-210
210-211
26
4
90
30
251-252
252-254
19
5
90
30
232-234
231-234
(Continued)

Polyhydroquinolines
305
Table 2
(
Continued)
26
6
90
40
258-260
260-263
26
7
81
25
253-255
255-258
2
3
8
9
93
79
30
35
178-179
184-186
178-180
184-186
26
34
1
0
81
35
193-195
192-193
(Continued)

3
06
Maleki et al.
Table 2
(
Continued)
28
1
1
92
25
160-162
158-160
ꢀ
mixture was heated on an oil bath at 110 C for the appropriate time (see Table 2). The
reaction progress was monitored by TLC (n-hexane:ethyl acetate, 2:1). After completion
of the reaction (as determined by TLC) we added 2 ml hot ethanol to the reaction mix-
ture and it was stirred for 2 minutes, then the Fe O @SiO /ZnCl was separated using
3
4
2
2
ꢀ
an external magnet and then dried at 110 C for 2 h. The resulting mixture was poured
into crushed ice, and the final product was obtained through filtration and pure product
was obtained by recrystallization from 96% ethanol.
Ethyl-1,4,7,8-tetrahydro-2,7,7-trimethyl-4-(phenyl)5-(6H)-oxoquinoline-3-carboxylate (5a)
À1
IR (KBr, disc) cm : 3300, 3200, 3100, 2980, 1700, 1620, 1490, 1390, 1300, 1200,
1
7
10; H-NMR (300 MHz, DMSO-d ) d 0.85 (s, 3H), 1.01 (s, 3H), 1.14 (t, 3H), 2.06
6
(
(
dd, 1H), 2.13 (dd, 1H), 2.28 (s, 2H), 3.18 (s, 3H), 3.98 (q, 2H), 4.91 (s, 1H), 6.90–7.22
13
m, 5Harom), 9.05 (s, 1H, NH, exchangeable with D O); C-NMR (75 MHz, DMSO-d6)
2
d 194.54, 166.82, 149.10, 147.12, 144.24, 127.21, 127.03, 125.06, 110.28; 104.09,
8.71, 50.18, 35.72, 31.77, 28.90, 26.32, 18.09, 13.67.
5
Acknowledgments
The authors thank the Research Council of Hakim Sabzevari University and the
University of Mazandaran for partial support of this work.
References
1
2
3
4
5
6
. C. R. Reddy and M. D. Reddy, J. Org. Chem., 79, 106 (2014).
. D. R. Motati, D. Uredi and E. B. Watkins, Chem. Sci., 9, 1728 (2018).
. M. D. Reddy, F. R. Fronczek, and E. B. Watkins, Org. Lett., 18, 5620 (2016).
. T. Godfraind, R. Miller, and M. Wibo, Pharmacol. Rev., 38, 321 (1986).
. R. A. Janis, P. J. Silver, and D. J. Triggle, Adv. Drug Res., 16, 309 (1987).
. P. P. Mager, R. A. Coburn, A. J. Solo, D. J. Triggle and H. Rothe, Drug Des. Discov., 8,
2
73 (1992).

Polyhydroquinolines
307
7
. R. Manmhold, B. Jablonka, W. Voigdt, K. Schoenafinger and E. J. Schraven, Med. Chem.,
7, 229 (1992).
2
8
. A. C. Gaudio, A. Korokovas and Y. J. Takahata, Pharm. Sci., 83, 1110 (1994).
. V. Klusa, Drugs Future, 20, 135 (1995).
9
1
1
1
1
0. F. R. Buhler and W. Kiowski, J. Hypertens., S3 (1987).
1. M. G. Dekamine, S. Ilkhanizadeh and S. Karimi, RSC Adv., 4, 56658 (2014).
2. B. Love and K. M. Snader, J. Org. Chem., 21, 1914 (1956).
3. F. Moeinpour, N. Dorostkar-Ahmai, A. Sardashti-Birjandi, A. Khojastehnezhad and M.
Vafaei, Res. Chem. Intermed., 9, 3145 (2014).
1
1
1
4. B. Maleki and S. Sheikh, RSC Adv., 54, 42997 (2015).
5. B. Maleki, S. Babaee and R. Tayebee, Appl. Organomet. Chem., 29, 408 (2015).
6. B. Maleki, E. Sheikh, E. Rezaei Seresht, H. Eshghi, S. Sedigh Ashrafi, A. Khojastehnezhad
and H.Veisi, Org. Prep. Proced. Int., 48, 37 (2016).
1
7. J. Safaei-Ghomi, M. Asgari-Keirabadi, B. Khojastehbakht-Koopaei and H. Shahbazi-Alavi,
Res. Chem. Intermed., 2, 827 (2016).
1
8. Z. Zarnegar, J. Safari and Z. Mansouri-Kafroudi, Catal. Commun., 59, 216 (2015).
1
9. S. Taghavi Fardood, A. Ramazani, Z. Golfar and S. W. Joo, Appl. Organomet. Chem., DOI:
1
0.1002/aoc.3823 (2017).
2
2
2
0. S. Ko and C.-F. Yao, Tetrahedron, 62, 729 (2006).
1. J.J. Xia and K.H. Zhang, Molecules, 17, 5339 (2012).
2. L. Nagarapu, M. D. Kumari, N. V. Kumari and S. Kantevari, Catal. Commun., 8, 1871
(
2007).
2
3. S. R. Cherkupally and R. Mekala, Chem. Pharm. Bull., 56, 1002 (2008).
2
4. L. S. Gadekar, S. S. Katkar, S. R .Mane, B. R. Arbad and M. K. Lande, Bull. Korean Chem.
Soc., 30, 2532 (2009).
2
2
2
5. M. Hong, C. Cai and W.-B. Yi, J. Fluorine Chem., 131, 111 (2010).
6. A. Khojastehnezhad, F. Moeinpour and A. Davoodnia, Chin. Chem. Lett., 22, 807 (2011).
7. M. Tajbakhsh, E. Alaee, H. Alinezhad, M. Khanian, F. Jahani, S. Khaksar, P. Rezaee and M.
Tajbakhsh, Chin. J. Catal., 33, 1517 (2012).
2
2
3
3
3
3
8. P. Kulkarni, J. Chil. Chem. Soc., 59, 2319 (2014).
9. A. Rajini, M. Nookaraju, I. A. Reddy and V. Narayanan, Chem. Pap., 68, 170 (2014).
0. A. Maleki, M. Kamalzare and M. Aghaei, J. Nanostruct. Chem., 5, 95 (2014).
1. A. Ghorbani-Choghamarani and G. Azadi, RSC Adv., 5, 9752–8 (2015).
2. B. Maleki, A. Vedad Mofrad and A. Khojastehnezhad, Heterocycl. Lett., 7, 17 (2017).
3. A. Khojastehnezhad, B. Maleki and A. Vedad Mofrad, Biointerface Res. Appl. Chem., 7,
2
030 (2017).
3
4. B. Maleki, R. Tayebee and M. Kermanian, J. Mex. Chem. Soc., 57, 290 (2013).

3
08
Maleki et al.
3
5. B. Maleki, R. Tayebee, Z. Sepehr and M. Kermanian, Acta Chim. Slov., 59, 814 (2012).
6. A. Khojastehnezhad, B. Maleki, B. Karrabi and E. Rezaei Seresht, Org. Prep. Proced. Int.,
3
4
9, 338 (2017).
3
3
3
4
7. B. Maleki and F. Taimazi, Org. Prep. Proced. Int., 46, 252 (2014).
8. B. Maleki, Org. Prep. Proced. Int., 47, 173 (2015).
9. B. Maleki and S. Sheikh, Org. Prep. Proced. Int., 47, 368 (2015).
0. B. Maleki, F. Mohammadi Zonos and H. A. Akhlaghi, Org. Prep. Proced. Int., 47, 361
(
2015).
4
4
4
4
1. B. Maleki, G. Esmailian and R. Tayebee, Org. Prep. Proced. Int., 47, 461 (2015).
2. B. Maleki, E. Rezaei Seresht and Z. Ebrahimi, Org. Prep. Proced. Int., 47, 149 (2015).
3. B. Maleki, Org. Prep. Proced. Int., 48, 303 (2016).
4. B. Maleki, M. Raei, E. Akbarzadeh, H. Ghasemnejad Borsa, A. Sedrpoushan, S. Sedigh
Ashrafi and M. N. Dehdashti, Org. Prep. Proced. Int., 48, 62 (2016).
4
5. H. Veisi, A. Naeimi, B. Maleki, S. Sedigh Ashrafi and A. Sedrpoushan, Org. Prep. Proced.
Int., 47, 309 (2015).
4
6. S. Hemmati, P. Mohammadi, A. Sedrpoushan and B. Maleki, Org. Prep. Proced. Int., 50,
4
65 (2018).
4
4
4
5
7. E. Roduner, Chem. Soc. Rev., 35,583 (2006).
8. L. L. Chng, N. Erathodiyil and J. Y. Ying, Acc. Chem. Res., 46, 1825 (2013).
9. S. K. Sahoo and V. Labhasetwar, Drug Discov. Today., 8. 1112 (2003).
0. V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara and J. M. Basset, Chem. Rev.,
1
11, 3036 (2011).
1. B. Maleki, N. Nasiri, R. Tayebee, A. Khojastehnezhad and H. A. Akhlaghi, RSC Adv., 6,
9128 (2016).
5
5
5
5
7
2. B. Maleki, H. Eshghi, M. Barghamadi, N. Nasiri, A. Khojastehnezhad, S. Sedigh Ashrafi and
O. Pourshiani, Res. Chem. Intermed., 44, 3071 (2016).
3. B. Maleki, M. Baghayeri, S. Ayazi Jannat Abadi, R. Tayebee and A. Khojastehnezhad, RSC
Adv., 6, 96644 (2016).
4. C. K. Bradsher, R. D. Brandau, J. E. Boliek and T. L. Hough, J. Org. Chem., 34, 2129
(
1969).
55. A. Katrib, C. Petit, P. Legare, L. Hilaire and G. Maire, Surf. Sci., 189, 886 (1987).
56. R. Lamber, N. Jaeger and G. Schulz -Ekloff, Surf. Sci., 26, 8227 (1990).
57. B. K. Min, A. K. Santral and D. W. Goodman, Catal. Today., 85, 113 (2003).
58. K. D. Kim, S. S. Kim, Y. H. Choa and H. T. Kim, J. Ind. Eng. Chem., 13, 1137 (2007).
59. M. Jafarzadeh, R. Adnan and M. K. N. Mazlan, J. Non. Cryst. Solids., 385, 2981 (2012).
60. J. Wang, B. Xu, H. Sun and G. Song, Tetrahedron Lett., 54, 238 (2013).
61. B. Li, L. Gao, F. Bian and W. Yu, Tetrahedron Lett., 54, 1063 (2013).
62. A. Maleki, Tetrahedron Lett., 54, 2055 (2013).

Polyhydroquinolines
309
6
6
6
3. J. Lee, Y. Lee and J. K. Youn, Biocompat. Mater., 4, 143 (2008).
4. E. Kim, J. Jang and J. S. Chung, Macromol. Res., 22, 864 (2014).
5. S. D. Pan, H. Y. Shen, L. X. Zhou, X. H. Chen, Y. G. Zhao, M. Q. Cai and M. C. Jin, J.
Mater. Chem., A2, 15345 (2014).
6
6
6
6
6. B. Guoyi, L. Xingwang and L. Xiaofang, Green Chem., 16, 3160 (2014).
7. A. Palani and J. S. Lee, J. Proteome Res., 7, 3591 (2008).
8. L. Rousseau, P. Matlaba and C. J. Parkinson, Tetrahedron Lett., 48, 4079 (2007).
9. E. Soleimani, M. Naderi Namivandi and H. Sepahvand. Appli. Organomet. Chem., 31 3566
(
2017).