Fe3O4@SiO2@propyl-ANDSA: A new catalyst for the synthesis of tetrazoloquinazolines

Article abstract of DOI:10.1002/aoc.4038

In this paper, a mild and green protocol has been developed for the synthesis of quinazoline derivatives. The catalytic activity of 7-aminonaphthalene-1,3-disulfonic acid-functionalized magnetic Fe₃O₄ nanoparticles (Fe₃O₄@SiO₂@Propyl–ANDSA) was investigated in the one-pot synthesis of new derivatives of tetrahydrotetrazolo[1,5-a]quinazolines and tetrahydrobenzo[h]tetrazolo[5,1-b]quinazolines from the reaction of aldehydes, 5-aminotetrazole, and dimedone or 6-methoxy-3,4-dihyronaphtalen-1(2H)-one at 100?°C in H₂O/EtOH as the solvent. The catalyst was characterized before and after the organic reaction. Fe₃O₄@SiO₂@Propyl–ANDSA showed remarkable advantages in comparison with previous methods. Advantages of the method presented here include easy purification, reusability of the catalyst, green and mild procedure, and synthesis of new derivatives in high yields within short reaction time.

Full text of DOI:10.1002/aoc.4038

Journal Code
Article ID
Dispatch: 00.00.00 CE:
8 No. of Pages: 10 ME:
A
O
C
4
0
3
Received: 3 June 2017
DOI: 10.1002/aoc.4038
Revised: 19 July 2017
Accepted: 19 July 2017
F U L L P A P E R
Fe3O4@SiO2@propyl‐ANDSA: A new catalyst for the
synthesis of tetrazoloquinazolines
Ramin Ghorbani‐Vaghei
| Sedigheh Alavinia | Narges Sarmast
Faculty of Chemistry, Bu‐Ali Sina
University, Hamedan 6517838683, Iran
In this paper, a mild and green protocol has been developed for the synthesis of
quinazoline derivatives. The catalytic activity of 7‐aminonaphthalene‐1,3‐disul-
fonic acid‐functionalized magnetic Fe3O4 nanoparticles (Fe3O4@SiO2@Propyl–
ANDSA) was investigated in the one‐pot synthesis of new derivatives of
tetrahydrotetrazolo[1,5‐a]quinazolines and tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazolines from the reaction of aldehydes, 5‐aminotetrazole, and dimedone
or 6‐methoxy‐3,4‐dihyronaphtalen‐1(2H)‐one at 100 °C in H2O/EtOH as the
solvent. The catalyst was characterized before and after the organic reaction.
Fe3O4@SiO2@Propyl–ANDSA showed remarkable advantages in comparison
with previous methods. Advantages of the method presented here include easy
purification, reusability of the catalyst, green and mild procedure, and synthesis
of new derivatives in high yields within short reaction time.
Correspondence
Ramin Ghorbani‐Vaghei, Faculty of
Chemistry, Bu‐Ali Sina University,
Hamedan 6517838683, Iran.
Email: rgvaghei@yahoo.com
KEYWORDS
green chemistry, magnetic nanoparticles, nano catalyst, quinazoline derivatives
1 | INTRODUCTION
and Cefazolin is an antibiotic used for the treatment of a
number of bacterial infections.[5]
The synthesis of organic compounds via green, mild, and
simple procedures is currently receiving significant
attention of chemists. In this regard, multicomponent
reactions have been emerged as highly valuable synthetic
routes for the rapid synthesis of diverse and complex
heterocyclic scaffolds.
In recent years, metal oxide nanostructures including
iron have attracted a great deal of attention. They have
been demonstrated to be applicable in catalyst technology
which cannot be usually achieved by their bulk
counterparts.[1]
The synthesis of new heterocyclic compounds has
been always a subject of great interest, due to their wide
applications. Quinazolines and their derivatives represent
one of the most important classes of heterocyclic com-
pounds possessing a wide range of pharmacological and
biological activities.[2] 5‐Amino‐tetrazole is known to be
a part of certain drugs such as Corazol, Cefazolin, and
Cefoperazone.[3] Cefoperazone is an effective antibiotic[4]
The reaction of keto acid esters with a mixture of
aromatic aldehydes and 5‐amino‐tetrazole is the main
method used for the synthesis of these heterocyclic
compounds.[6]
The reaction of methyl esters of acylpyruvic acids with
5‐amino‐tetrazole or 3‐amino‐1,2,4‐tetrazole proceeds
similarly to give quinazoline derivatives.[7] Furthermore,
it has been found that fusion of various acetylacetate with
a mixture of aromatic aldehydes and 5‐amino‐tetrazole
affords dihydrotetrazolo[1,5‐a]pyrimidine derivatives.[8]
These methods have been accomplished in the presence
of different catalysts such as p‐TSA,[9] acetic acid,[10] and
I2.[11] Although these protocols find certain merits of their
own, they still suffer from a number of disadvantages such
as the use of expensive or toxic catalysts, high reaction
temperatures, low product yields and long reaction times.
Therefore, there is still a demand for simple and facile
synthetic methods in order to obtain these heterocyclic
compounds under green reaction conditions.
Appl Organometal Chem. 2017;e4038.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
1 of 10
https://doi.org/10.1002/aoc.4038

2 of 10
GHORBANI‐VAGHEI ET AL.
In the present study, an efficient procedure has been
vibrating sample magnetometry (VSM) was utilized
(MDKFT instrument).
described for the synthesis of tetrahydrotetrazolo[1,5‐a]
quinazolines and tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazolines in excellent yields from the reaction of alde-
hydes, 5‐aminotetrazole, and dimedone or 6‐methoxy‐3,4‐
dihyronaphtalen‐1(2H)‐one at 100 °C in H2O/EtOH as the
solvent. 7‐Aminonaphthalene‐1,3‐disulfonic acid‐func-
2.2 | Preparation of 7‐aminonaphthalene‐
1,3‐disulfonic acid‐functionalized magnetic
Fe3O4 nanoparticles (Fe3O4@SiO2@propyl–
ANDSA)
tionalized
Fe3O4
magnetic
nanoparticles
(Fe3O4@SiO2@Propyl–ANDSA)[12] was utilized as a novel
catalyst in these reactions (Figure 1). With its operational
simplicity, green nature, and high yields the reaction will
be acting as an attractive alternative for the synthesis of
tetrazoloquinazolines.
There are totally four major steps for the synthesis
procedure of the magnetic Fe3O4@SiO2@Propyl–ANDSA.
Firstly, naked magnetic Fe3O4 nanoparticles were
prepared through coprecipitation of iron(II) and iron(III)
ions.[13] Secondly, the magnetic NPs were coated with a
silica shell by using tetraethylorthosilicate (TEOS).
Thirdly, the Fe3O4@SiO2 nanoparticles were coated by
(3‐chloropropyl)‐triethoxysilane, yielding the chloro
functionalized nanoparticles (Fe3O4@SiO2@Cl MNPs).[14]
Finally, the Fe3O4@SiO2@Cl nanoparticles reacted with
2 | EXPERIMENTAL SETUP
2.1 | Chemicals and instruments
All commercially available chemicals were obtained from
Merck and Fluka companies, and used without further
purification unless otherwise stated. Nuclear magnetic
resonance (NMR) spectra were recorded in DMSO‐d6 on
Bruker Avancespectrometers of 90 MHz, 400 MHz for
1H NMR and 75 MHz and 100 MHz for 13C NMR using
TMS as an internal standard; chemical shifts were
expressed in parts per million (ppm). Mass spectra were
recorded on a Shimadzu QP 1100 BX Mass Spectrometer.
Melting points were determined on a Stuarf Scientific
SMP3 apparatus. Elemental analyses, (C, H, N) were
performed with a Heraeus CHN‐O‐Rapid analyzer.
Fourier transform infrared (FT‐IR) spectra were recorded
with a Shimadzu 435‐U‐04 FT spectrophotometer from
KBr pellets. Scanning electron microscopy (SEM) was
performed on EM3200 instrument operated at 30 kV
accelerating voltage. The qualitative analysis of
Fe3O4@SiO2@Propyl–ANDSA was performed by using
energy‐dispersive X‐ray spectroscopy (EDX). Energy
dispersive X‐ray analysis of the prepared catalyst was
performed on a FESEM‐SIGM (Germany) instrument.
To measure the magnetic attributes of the samples,
7‐aminonaphthalene‐1,3‐disulfonic
acid
to
yield
Fe3O4@SiO2@Propyl–ANDSA.[12] The acidic content of
Fe3O4@SiO2@Propyl–ANDSA was characterized by
determination of H+ of the catalyst through back titration
with NaOH (0/1 mol/L). The mol% H+ of catalyst was
found to be 1.8 and 1.65 mol%, before and after recycling,
respectively.
2.3 | General procedure for the synthesis
of tetrazoloquinazolines using
Fe3O4@SiO2@propyl–ANDSA
A mixture of substituted benzaldehyde (1 mmol), 2‐amino
tetrazole (1 mmol), and dimedone (1 mmol) or
6‐methoxy‐3,4‐dihydronaphtalen‐1(2H)‐one (1 mmol) in
H2O: EtOH (1:1) as the solvent (2 mL) and in the presence
of Fe3O4@SiO2@Propyl–ANDSA (0.2 g ~ 1.8 mol%) was
stirred for appropriate time at 100 °C. After completion
of the reaction, the nanocatalyst was separated using an
external magnet. Subsequently, the solvent was
evaporated and 95% EtOH (5 mL) was added. The
precipitate was then filtered off and washed with cold
FIGURE 1 The structures of
Fe3O4@SiO2@Propyl–ANDSA.

GHORBANI‐VAGHEI ET AL.
3 of 10
ethanol. After drying, the pure product was obtained and
characterized via different techniques.
2.4.4 | 6,6‐Dimethyl‐9‐(3‐bromophenyl)‐
5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazolin‐
8(4H)‐one
White solid, 5f, mp: 243‐244 °C. 1HNMR (90 MHz,
DMSO‐d6): δH (ppm) 1.00 (s,CH3, 3H), 1.04 (s, CH3, 3H),
2.19 (s, CH2, 2H), 2.60 (s, CH2, 2H), 6.62 (s, CH, 1H),
7.24–7.54 (m, CH aromatic,4H), 11.65 (s, NH, 1H), 13C
NMR (75 MHz, DMSO‐d6): δc (ppm): 27.30, 28.60, 32.70,
50.10, 57.37, 105.48, 122.15, 126.61, 130.55, 131.40,
131.80, 143.11, 148.73, 151.68, 194.05, ppm; Mass (m/z):
373, Anal. Calcd for C16H16 BrN5O: C, 51.35; H, 4.31; N,
18.71. Found: C,51.36; H, 4.23; N, 18.62.
2.4 | Analytical data of selected products
2.4.1 | 6,6‐Dimethyl‐9‐(2‐methoxyphenyl)‐
5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazolin‐
8(4H)‐one
White solid, 5b, mp: 277‐279 °C. 1HNMR (90 MHz,
DMSO‐d6): δH (ppm) 0.92 (s,CH3, 3H), 1.04 (s, CH3, 3H),
2.09 (s, CH2, 2H), 2.52 (s, CH2, 2H), 3.61 (s, OCH3, 3H),
6.67 (s, CH, 1H), 6.88–7.42 (m, CH aromatic,4H), 11.47
(s, NH, 1H), 13C NMR (75 MHz, DMSO‐d6): δc (ppm)
26.60, 29.13, 32.59, 50.34, 55.60, 55.92, 105.16, 112.09,
120.50, 127.86, 130.30, 130.66, 149.61, 151.17, 157.51,
193.22, ppm; Mass (m/z): 325, Anal. Calcd for
C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C,62.70;
H, 5.91; N; 21.29.
2.4.5 | 3‐Methoxy‐7‐(3‐methoxyphenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6a, mp: 258‐260 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.8 (ddd, J = 10.0, 6.4, 4.0 Hz, CH,
1H), 2.19 (t, J = 7.2 Hz, CH, 1H), 2.64 (t, J = 7.2 Hz,
CH, 1H), 2.75 (ddd, J = 10.0, 6.4, 4.0 Hz, CH, 1H), 3.74
(s, OCH3, 3H), 3.78 (s, OCH3, 3H), 6.41(s, CH, 1H), 6.84
(ddd, J = 11.6, 9.2, 6.4 Hz, CH aromatic, 1H), 6.92–6.95
(m, CH aromatic, 4H), 7.32 (dd, J = 16.0, 8.0 Hz, CH
aromatic, 1H), 7.65 (d, J = 8.8 Hz, CH aromatic, 1H),
10.40 (s, NH, 1H). 13C NMR (100 MHz, DMSO‐d6): δc
(ppm) 24.06, 28.16, 55.62, 55.67, 56.18, 61.84, 104.07,
111.71, 114.02, 114.28, 119.89, 121.59, 123.88, 127.51,
130.74, 138.44, 141.41, 150.95, 159.76, 159.97 ppm; Mass
(m/z): 361, Anal. Calcd for C20H19N5O2:C, 66.47; H,
5.30; N, 19.38. Found: C, 66.14; H, 4.72; N, 19.36.
2.4.2 | 6,6‐Dimethyl‐9‐(3‐methoxyphenyl)‐
5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazolin‐
8(4H)‐one
White solid, 5c, mp: 232‐233 °C. 1HNMR (90 MHz,
DMSO‐d6): δH (ppm) 1.01 (s,CH3, 3H), 1.06 (s, CH3, 3H),
2.20 (s, CH2, 2H), 2.60 (s, CH2, 2H), 3.71 (s, OCH3, 3H),
6.56 (s, CH, 1H), 6.85–7.33 (m, CH aromatic,4H), 11.55
(s, NH, 1H), 13C NMR (75 MHz, DMSO‐d6): δc (ppm):
27.39, 28.77, 32.74, 50.28, 55.54, 57.74, 105.97, 113.80,
119.64, 130.26, 142.31, 148.88, 151.04, 159.73,
193.48 ppm; Mass (m/z): 325, Anal. Calcd for
C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C, 62.80;
H, 5.84; N, 21.54.
2.4.6 | 3‐Methoxy‐7‐(4‐fluorophenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6b, mp: 256‐257 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.80 (t, J = 6.4 Hz, CH, 1H), 2.16
(ddd, J = 16.0, 10.0, 8.0 Hz, CH, 1H), 2.65 (t,
J = 7.2 Hz, CH, 1H), 2.72–2.80 (ddd, J = 16.0, 9.6,
6.0 Hz, CH, 1H), 3.3 (s, OCH3, 3H), 6.50 (s, CH, 1H),
6.85 (ddd, J = 11.6, 7.6, 2.8 Hz, CH, 1H), 6.9 (ddd,
J = 11.6, 7.6, 2.8 Hz, CH, 1H), 7.23(d, J = 8.8 Hz, CH
aromatic, 2H),7.34 (d, J = 8.8 Hz, CH aromatic, 2H),
7.66 (d, J = 8.8 Hz, CH aromatic, 1H), 10.44 (s, NH,
1H). 13C NMR (100 MHz, DMSO‐d6): δc (ppm) 24.06,
28.15, 55.66, 61.15, 103.76, 111.71, 114.27, 116.23,
116.44, 121.56, 123.95, 127.71, 130.20, 130.29, 136.06,
136.08, 138.43, 150.87, 159.80, 161.40, 163.83 ppm; Mass
(m/z): 349, Anal. Calcd for C19H16 FN5O: C, 65.32; H,
4.62; N, 20.05. Found: C, 65.81; H, 4.26; N, 19.59.
2.4.3 | 6,6‐Dimethyl‐9‐(2,3‐
dichlorophenyl)‐5,6,7,9‐
tetrahydrotetrazolo[1,5‐a]quinazolin‐8(4H)‐
one
White solid, (5e), mp: 305‐307 °C. 1HNMR (90 MHz,
DMSO‐d6): δH (ppm) 1.01 (s,CH3, 3H), 1.05 (s, CH3,
3H), 2.16 (s, CH2, 2H), 2.58 (s, CH2, 2H), 6.97 (s, CH,
1H), 7.38–7.61 (m, CH aromatic,3H), 11.72 (s, NH,
1H), 13C NMR (75 MHz, DMSO‐d6): δc (ppm) 27.52,
28.64, 32.66, 50.23, 55.82, 104.71, 128.07, 129.74,
132.62, 133.67, 134.30, 136.50, 149.01, 151.83, 193.41,
ppm; Mass (m/z): 364, Anal. Calcd for C16H15 Cl2N5O:
C, 52.76; H, 4.15; N, 19.23. Found: C,52.74; H, 3.99;
N, 19.24.

4 of 10
GHORBANI‐VAGHEI ET AL.
CH, 1H), 2.16 (ddd, J = 16.8, 10.2, 8.0 Hz, CH, 1H), 2.57
(ddd, J = 5.2, 3.6, 1.6 Hz, CH, 1H), 2.74 (ddd, J = 16.0,
10.0, 6.8 Hz, CH, 1H), 3.70 (s, OCH3, 3H), 3.77 (s, OCH3,
3H), 6.61(s, CH, 1H), 6.8 (ddd, J = 16.0, 8.4, 2.8 Hz, CH
aromatic, 1H), 6.86 (ddd, J = 16.0, 8.4, 2.8 Hz, CH
aromatic, 1H), 6.96(ddd, J = 8.4, 7.2, 6.4 Hz, CH aromatic,
1H), 7.00 (d, J = 8.0 Hz, CH, 1H) 7.21 (s, CH aromatic,
1H), 7.34 (ddd, J = 7.6, 2.4, 2.0 Hz, CH, 1H), 7.63 (d,
J = 8.8 Hz, CH, 1H), 10.30 (s, NH, 1H). 13C NMR
(100 MHz, DMSO‐d6): δc (ppm) 23.93, 28.19, 55.63,
56.31, 103.69, 111.64, 112.52, 114.21, 121.23, 121.89,
123.64, 127.32, 127.49, 129.48, 130.67, 138.30, 151.59,
157.67, 159.58 ppm; Mass (m/z): 361, Anal. Calcd for
C20H19N5O2: C, 66.47; H, 5.30; N, 19.38. Found: C,65.94;
H, 5.04; N, 19.33.
2.4.7 | 3‐Methoxy‐7‐(2‐methoxyphenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
Cream solid, 6c, mp: 270‐272 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.77 (ddd, J = 16.0, 10.2, 6.8 Hz,
2.4.8 | 3‐Methoxy‐7‐(4‐methylphenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6d, mp: 257‐258 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.79 (ddd, J = 16.0, 10.0, 6.4 Hz,
CH, 1H), 2.15 (ddd, J = 22.2, 16.8, 9.6 Hz, CH, 1H), 2.28
SCHEME
1
One‐pot synthesis of tetrahydrotetrazolo[1,5‐a]
quinazolines and tetrahydrobenzo[h]tetrazolo[5,1‐ b]quinazolines
TABLE 1 Optimizing the reaction conditions for the synthesis of 9‐(4‐chlorophenyl)‐6,6‐dimethyl‐5,6,7,9‐tetrahydrotetrazolo[1,5‐a]
quinazolin‐8(4H)‐one 5a using Fe3O4@SiO2@propyl–ANDSA as the catalyst
Entry
Catalyst
Conditions
Time (min)
Yielda (%)
b
1
‐
100 °C
6
‐
2
AlCl3 (5 mol%)
EtOH, reflux
100 °C
100 °C
100 °C
100 °C
100 °C
100 °C
100 °C
90 °C
5
10
10
10
5
Trace
80
86
90
94
90
85
70
90
94
92
92
75
80
75
88
80
3
MNPs@SiO2‐Pr‐ANDSA (0.05 g)c
MNPs@SiO2‐Pr‐ANDSA (0.1 g)c
MNPs@SiO2‐Pr‐ANDSA (0.15 g)c
MNPs@SiO2‐Pr‐ANDSA (0.2 g)c
MNPs@SiO2‐Pr‐ANDSA (0.25 g)c
MNPs@SiO2‐Pr‐ANDSA (0.3 g)c
MNPs@SiO2 (0.2 g)c
4
5
6
7
5
8
5
9
15
5
10
11
12
13
14
15
16
17
18
MNPs@SiO2‐Pr‐ANDSA (0.2 g)c
MNPs@SiO2‐Pr‐ANDSA (0.2 g)c
MNPs@SiO2‐Pr‐ANDSA (0.2 g)d
MNPs@SiO2‐Pr‐ANDSA (0.2 g)d
MNPs@SiO2‐Pr‐ANDSA (0.2 g)d
MNPs@SiO2‐Pr‐ANDSA (0.2 g)
MNPs@SiO2‐Pr‐ANDSA (0.2 g)
MNPs@SiO2‐Pr‐ANDSA (0.2 g)
Fe3O4@SiO2‐SO3Hc
110 °C
120 °C
130 °C
100 °C
MeCN
H2O
5
5
5
5
5
10
5
EtOH
100 °C
15
aIsolated yield.
bNo reaction accrued.
cReaction condition: 4‐chlorobenzaldehyde (1 mmol), 2‐aminotetrazole (1 mmol), and dimedone (1 mmol) in H2O/EtOH (1:1).
dReaction condition: 4‐chlorobenzaldehyde (1 mmol), 2‐aminotetrazole (1 mmol), and dimedone (1 mmol) in solvent‐free condition.

GHORBANI‐VAGHEI ET AL.
5 of 10
TABLE 2 Synthesis of tetrahydrotetrazolo[1,5‐a]quinazolines 5a–f and tetrahydrobenzo[h]tetrazolo[5,1‐b]quinazolines 6a–h using
Fe3O4@SiO2@propyl–ANDSAa
Compd.
5a
G
Time (min)
Yieldb (%)
m.p.
m.p.Ref
254–255[10]
4‐Cl
5
94
259–260
5b
5c
5d
5e
5f
2‐OMe
3‐OMe
2,4‐Cl2
2,3‐Cl2
3‐Br
10
10
20
30
40
15
10
25
20
55
70
35
8
85
90
94
92
90
90
85
88
90
85
85
85
90
277–279
232–233
280–281
305–307
243–244
258–260
256–257
270–272
257–258
262–263
272–274
243–245
258–259
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
>270[10]
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
6a
6b
6c
6d
6e
6f
3‐OMe
4‐F
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
2‐OMe
4‐Me
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
3,4,5‐(OMe)3
2‐Cl
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
6g
6h
4‐OMe
3‐Cl
‐‐‐‐‐‐‐
‐‐‐‐‐‐‐
aReaction condition: aldehydes (1 mmol), 5‐aminotetrazole (1 mmol), and 6‐methoxy‐3,4‐dihyronaphtalen‐1(2H)‐one (1 mmol), or dimedone (1 mmol).
bIsolated yield.
TABLE 3 Comparison of different methods in the synthesis of 6,6‐dimethyl‐9‐aryl‐5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazoline‐8(4H)‐one
5a
Entry
Catalyst
Solvent
Conditions
Time
Yield (%)
Ref.
[11]
1
I2
Isopropyl alcohol
Reflux
10 min
92
[9]
2
3
p‐TSA
Solvent‐free
80 °C
6 min
5 min
88
94
Fe3O4@SiO2@propyl–ANDSA
H2O/EtOH (1:1)
100 °C
This work
(s, CH3, 3H), 2.63 (ddd, J = 16.2, 10.2, 6.8 Hz, CH, 1H),
2.74 (ddd, J = 16.0, 10.0, 6.4 Hz, CH, 1H), 3.77 (s, OCH3,
3H), 6.40 (s, CH, 1H), 6.83 (d, J = 2.4 Hz, CH, 1H), 6.87
(dd, J = 8.8, 2.8 Hz, CH, 1H), 7.19 (d, J = 8.4 Hz, CH aro-
matic, 2H), 7.22 (d, J = 8.4 Hz, CH aromatic, 2H), 7.64 (d,
J = 8.8 Hz, CH, 1H), 10.38 (s, NH, 1H). 13C NMR
(100 MHz, DMSO‐d6): δc (ppm) 20.69, 23.62, 27.67,
55.15, 61.21, 103.66, 111.18, 113.76, 121.07, 123.36,
126.86, 127.43, 129.47, 136.45, 137.88, 138.18,
159.22 ppm; Mass (m/z): 345, Anal. Calcd for
C20H19N5O: C, 69.55; H, 5.54; N, 20.28. Found: C,69.58;
H, 5.54; N, 20.34.

6 of 10
GHORBANI‐VAGHEI ET AL.
SCHEME 2 The suggested mechanism
for the synthesis of
tetrahydrotetrazolo[1,5‐a]quinazolines 5a–
f in the presence of Fe3O4@SiO2@propyl–
ANDSA
CH, 1H), 6.65 (s, CH, 1H), 6.84 (d, J = 2.8 Hz, 1H), 6.88
(dd, J = 2.8, 2.4 Hz, 1H), 7.65 (d, J = 8.8 Hz, 1H), 10.38
(s, NH, 1H). 13C NMR (100 MHz, DMSO‐d6): δc (ppm)
23.52, 27.79, 55.16, 55.89, 59.92, 61.68, 103.36, 104.85,
111.20, 113.77, 121.10, 123.41, 127.07, 134.92, 137.59,
138.04, 153.16, 159.26 ppm; Mass (m/z): 421, Anal. Calcd
for C22H23N5O4: C, 62.70; H, 5.50; N, 16.62. Found: C,
62.26; H, 5.11; N, 16.64.
2.4.10 | 3‐Methoxy‐7‐(2‐chlorophenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6f, mp: 272‐274 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.71 (ddd, J = 16.0, 10.0, 6.8 Hz,
CH, 1H), 2.13 (ddd, J = 16.0, 11.6, 4.4 Hz, CH, 1H), 2.62
(ddd, J = 15.2, 15.0, 7.2 Hz, CH, 1H), 2.76 (ddd,
J = 16.0, 10.4, 6.8 Hz, CH, 1H), 3.77 (s, OCH3, 3H), 6.80
(s, CH aromatic, 1H), 6.82 (d, J = 2.4 Hz, CH aromatic,
1H), 6.87 (dd, J = 2.8, 2.4 Hz, CH aromatic, 2H), 7.40 (s,
CH aromatic, 1H), 7.41 (d, J = 2.8 Hz, CH aromatic,
1H), 7.49 (s, CH aromatic, 1H), 7.65 (d, J = 8.4 Hz, CH
aromatic, 2H), 10.50 (s, NH, 1H). 13C NMR (100 MHz,
DMSO‐d6): δc (ppm) 23.26, 27.55, 55.16, 111.22, 113.75,
120.95, 121.01, 123.38, 127.94, 127.98, 128.04, 130.30,
130.35, 130.70, 132.33, 137.88, 159.29 ppm; Mass (m/z):
365, Anal. Calcd for C19H16 ClN5O: C, 62.38; H, 4.41; N,
19.14. Found: C, 62.15; H, 4.23; N, 19.15.
FIGURE 2 EDX spectra of Fe3O4@SiO2@propyl–ANDSA before
(a) and after (b) the reaction
2.4.9 | 3‐Methoxy‐7‐(3,4,5‐
trimethoxyphenyl)‐5,6,7,12‐
tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
2.4.11 | 3‐Methoxy‐7‐(4‐methoxyphenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6g, mp: 243‐245 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.8 (ddd, J = 16.0, 10.0, 6.4 Hz,
White solid, 6e, mp: 262‐263 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.86 (ddd, J = 15.6, 8.8, 6.4 Hz,
CH, 1H), 2.18 (ddd, J = 16.0, 7.6, 6.8 Hz, CH, 1H), 2.67
(ddd, J = 15.2, 8.8, 6.4 Hz, CH, 1H), 2.75 (ddd, J = 15.2,
8.8, 6.4 Hz, CH, 1H), 3.65–3.78 (m, OCH3, 12H), 6.36 (s,

GHORBANI‐VAGHEI ET AL.
7 of 10
FIGURE 3 FT‐ IR spectra of
Fe3O4@SiO2@propyl–ANDSA before (a)
and after (b) the reaction
2.0 Hz, CH aromatic, 1H), 6.94 (d, J = 8.4 Hz, CH aro-
matic, 2H), 7.26 (d, J = 8.4 Hz, CH aromatic, 2H), 7.64
(d, J = 8.4 Hz, CH aromatic, 1H), 10.37 (s, NH, 1H). 13C
NMR (100 MHz, DMSO‐d6): δc (ppm) 23.66, 27.69, 55.11,
55.16, 60.93, 103.76, 111.17, 113.76, 114.24, 121.10,
123.35, 128.83, 131.34, 137.89,159.44 ppm; Mass (m/z):
365, Anal. Calcd for C20H19N5O2: C, 62.47; H, 5.30; N,
19.38. Found: C, 62.08; H, 5.21; N, 19.12.
2.4.12 | 3‐Methoxy‐7‐(3‐chlorophenyl)‐
5,6,7,12‐tetrahydrobenzo[h]tetrazolo[5,1‐b]
quinazoline
White solid, 6h, mp: 258‐259 °C. 1HNMR (400 MHz,
DMSO‐d6): δH (ppm) 1.79 (ddd, J = 16.4, 10.4, 6.4 Hz,
CH, 1H), 2.17 (ddd, J = 16.8, 14.8, 7.2 Hz, CH, 1H), 2.64
(ddd, J = 16.0, 15.2, 6.8 Hz, CH, 1H), 2.75 (ddd,
J = 16.0, 10.4, 6.4 Hz, CH, 1H), 3.77 (s, OCH3, 3H), 6.51
(s, CH, 1H), 6.83 (d, J = 2.4 Hz, CH aromatic, 1H), 6.88
(dd, J = 2.8, 2.4 Hz, CH aromatic, 1H), 7.28 (ddd,
J = 5.6, 4.0, 2.4 Hz, CH aromatic, 1H), 7.34 (s, CH
aromatic, 1H), 7.45 (m, CH aromatic, 1H), 7.6 (d,
J = 8.4 Hz, CH aromatic, 1H), 2.48 (s, NH, 1H). 13C
NMR (100 MHz, DMSO‐d6): δc (ppm): 23.45, 27.61,
55.17, 60.73, 102.78, 111.23, 113.78, 120.90, 120.97,
123.52, 126.19, 127.43, 128.86, 131.04, 133.49, 137.93,
141.61, 150.34, 150.43, 159.34 ppm; Mass (m/z): 365, Anal.
Calcd for C19H16ClN5O: C, 62.38; H, 4.41; N, 19.14.
Found: C, 62.25; H, 4.24; N, 19.12.
FIGURE 4 SEM images of Fe3O4@SiO2@propyl–ANDSA before
(a) and after (b) the reaction
3 | RESULTS AND DISCUSSION
CH, 1H), 2.13 (ddd, J = 16.0, 13.6, 6.8 Hz, CH, 1H), 2.64
(ddd, J = 16.0, 15.2, 7.2 Hz, CH, 1H), 2.74 (ddd,
J = 16.0, 10.4, 6.8 Hz, CH, 1H), 3.74 (s, OCH3, 3H), 3.77
(s, OCH3, 3H), 6.39 (s, CH, 1H), 6.87 (dd, J = 2.4,
As a part of our continuing effort toward the synthesis of
tetrazolopyrimidine derivatives[15] and other organic
compoundes, and in continuation of our interest in the

8 of 10
GHORBANI‐VAGHEI ET AL.
FIGURE 5 XRD pattern of Fe3O4@SiO2@propyl–ANDSA after the reaction
application of nano catalysts in organic reactions,[16]
aldehydes under optimized conditions. As shown in
Table 2, both electron‐rich and electron‐deficient alde-
hydes gave tetrahydrotetrazolo[1,5‐a]quinazolines and
tetrahydrobenzo[h]tetrazolo[5,1‐b]quinazolines with sat-
isfactory yields.
Literature surveys revealed that various catalysts such
as I2 and p‐TSA have been employed in this reaction as
demonstrated in Table 3. It is obvious from the results
that the products were obtained in high yields within
shorter reaction times in the current work in comparison
with other reported procedures. Therefore, the use of
Fe3O4@SiO2@Propyl–ANDSA can significantly improve
the product yields and decrease reaction time.
herein,
we
describe
the
synthesis
of
tetrahydrotetrazolo[1,5‐a]quinazolines
and
tetrahydrobenzo[h]tetrazolo[5,1‐b]quinazolines through
the condensation reaction of substituted aldehydes, 5‐
aminotetrazole, and dimedone or 6‐methoxy‐3,4‐
dihyronaphtalen‐1(2H)‐one
in the
presence
of
Fe3O4@SiO2@Propyl–ANDSA (Scheme 1).
Initially, MNPs@SiO2 was synthesized through a mod-
ified method of Stöber,[13] and subsequently, it was func-
tionalized with 7‐aminonaphthalene‐1,3‐disulfonic acid
to obtain Fe3O4@SiO2@Propyl–ANDSA. Then, the effect
of Fe3O4@SiO2@Propyl–ANDSA as catalyst was investi-
gated in the synthesis of 9‐(4‐chlorophenyl)‐6,6‐dimethyl‐
5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazolin‐8(4H)‐one
5a. First, the reaction progress was examined in the absence
of catalyst and it was observed that the reaction could not
proceed without the catalyst even after a prolonged reaction
time (Table 1, entry 1). According to Table 1, it was
determined that 0.2 g of catalyst is optimal to this reaction,
meanwhile less than 0.2 g of the catalyst leads to the low
reaction yield (Table 1, entries 3–5). In addition, the yield
of product did not increase by increasing the catalyst to
more than 0.2 g (Table 1, entries 7–8). Furthermore,
different temperatures were tested in this reaction
(Table 1, entries 10–13) and it was found that 100 °C is
the optimal temperature for this reaction (Table 1, entry
6). Then, the effect of different solvents was investigated
(Table 1, entries 15–17) and it was concluded that
H2O/EtOH (1:1) is the best choice. In addition, the reac-
tion in the presence MNPs@SiO2 was less progress com-
pared with MNPs@SiO2‐Pr‐ANDSA (Table 1, entry 9).
Thus the best result was achieved in the presence of
Fe3O4@SiO2@Propyl–ANDSA (0.2 g) in H2O/EtOH
(1:1) as solvent (Table 1, entry 6). All products were fully
In
the
next
step,
the
recyclability
of
Fe3O4@SiO2@Propyl–ANDSA was evaluated in the
model reaction. The reusability was tested up to seven
consecutive cycles for the synthesis of 6,6‐dimethyl‐9‐
aryl‐5,6,7,9‐tetrahydrotetrazolo[1,5‐a]quinazoline‐8(4H)‐
one 5a under the optimized reaction conditions and no
significant decrease in activity was observed (94, 93, 93,
91, 90, 88, and 86, respectively) and the amount of catalyst
that has been used in each cycle was 0.2 g. After completion
of the reaction, the catalyst was recovered by washing with
EtOH and H2O and then dried at 50–60 °C in an oven to be
used for seven continuous runs.
The proposed mechanism in the presence of
Fe3O4@SiO2@Propyl–ANDSA is shown in Scheme 2. It
is likely that this catalyst released H+, which can act as
electrophilic species. The initiation step begins with the
protonation of aldehydes which in Knoevenagel
condensation with dimedone results in the formation of
benzylidene compound. Next, Michael addition of
5‐aminotetrazole to this intermediate followed by next
cyclization results in the final ring system.
The catalyst was analyzed by different methods such as
scanning electron microscopy (SEM), transmission
electron microscopy (TEM), FT‐IR spectroscopy, energy‐
dispersive X‐ray spectroscopy (EDX), thermogravimetric
analysis (TGA) and vibrating sample magnetometry
1
charectrized on the basis of their spectroscopic data: H
NMR, 13C NMR, MS and (C, H, N) elemental analysis.
These results encouraged us to investigate the scope
and generality of this protocol for various aromatic

GHORBANI‐VAGHEI ET AL.
9 of 10
FIGURE 6 Magnetization curves of (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2@propyl, and (d) Fe3O4@SiO2@propyl–ANDSA
(VSM) confirming the successful synthesis of
Fe3O4@SiO2@Propyl–ANDSA.[12] In addition, the catalyst
was characterized after the reaction to compare with its
structure before reaction. Fe3O4@SiO2@Propyl–ANDSA
was collected after the reaction and subjected to different
analyses. The EDX spectra of the catalyst before and after
reaction are shown in Figure 2. The EDX spectra of catalyst
before and after reaction were almost identical which
indicated that there was no obvious change for the catalyst
composition after the reaction. In both spectra, the peaks
related to O, Si, and Fe elements are present and the
characteristic peaks of S and N in Figure 4 indicate that
the iron oxide nanoparticles have been successfully coated
with ANDSA.
20°, 25.5°, 27.5°, 29°, 30.5° and 32° implies that the
original structure of Fe3O4@SiO2@Propyl–ANDSA was
successfully preserved after the organic reaction.
The magnetic properties of four major steps in the
synthesis of the catalyst were provided via VSM. The
magnetization
curves
of
Fe3O4,
Fe3O4@SiO2,
Fe3O4@SiO2@Propyl, and Fe3O4@SiO2@Propyl–ANDSA
are shown in Figure 6. The saturation magnetization
value of catalyst was found to be 10 emu g−1 (Figure 6
d), which is lower than the obtained values for Fe3O4,
Fe3O4@SiO2, and Fe3O4@SiO2@Propyl.
4 | CONCLUSION
The FT‐IR spectra of the catalyst before and after
reaction are shown in Figure 3. For FT‐IR spectrum, the
major bands attributed to Fe─O and O─H stretching
vibrations, the presence of sulfonyl moieties, and the
characteristic peaks of silica framework were all observed
which indicated that the structure of catalyst did not
change after the reaction.
Figure 4 displays the SEM images of the catalyst
before and after the reaction revealing the maintenance
of the morphology of nearly spherical nanoparticles with
nanometric dimensions after the reaction.
In conclusion, we have developed an efficient and
environmental friendly procedure for the synthesis of
novel tetrazolo quinazoline derivatives from the reaction
of various aldehydes, 5‐aminotetrazole, and dimedone or
6‐methoxy‐3,4‐dihyronaphtalen‐1(2H)‐one. The method
provided several advantages including excellent product
yields, short reaction times, easy purification, recyclability
of the catalyst, and simple procedure. The application of
Fe3O4@SiO2@Propyl–ANDSA as the catalyst showed
efficient catalytic activity for the synthesis of quinazolines
due to the presence of two‐SO3H groups of the catalyst
which provided efficient acidic sites and excellent
catalytic activities.
Figure 5 shows the X‐ray diffraction pattern of the
catalyst after the reaction. The positions and relative
intensities of all characteristic diffractions at 2θ values of

10 of 10
GHORBANI‐VAGHEI ET AL.
[9] A. Hassankhani, E. Mosaddegh, Sci. Iran. 2015, 22, 942.
ACKNOWLEDGEMENTS
[10] M. Boutros, R. Maskey, S. Steinbrink, D. Gilbert, 2011, 56–57
We are thankful to Bu‐Ali Sina University, Center of
Excellence in Development of Environmentally Friendly
Methods for Chemical Synthesis (CEDEFMCS) for
financial support.
Patent WO2011/121096.
[11] L. Y. Zeng, C. Cai, J. Comb. Chem. 2010, 12, 35.
[12] R. Ghorbani‐Vaghei, N. Sarmast, J. Mahmoodi, Appl.
Organomet. Chem. 2016, In press, https://doi.org/10.1002/
aoc.3681.
[13] W. Stöber, A. Fink, E. Bohn, J. Colloid Interface Sci. 1968, 26, 62.
ORCID
[14] M. E. Mahmoud, M. S. Abdelwahab, E. M. Fathallah, Chem.
Eng. J. 2013, 223, 318.
Ramin Ghorbani‐Vaghei http://orcid.org/0000-0001-8322-
6299
[15] R. Ghorbani‐Vaghei, Z. Toghraei‐semiromi, M. Amiri, R.
Karimi‐Nami, Mol. Diversity 2013, 17, 307.
[16] (a) R. Ghorbani‐Vaghei, S. Hemmati, M. Hamelian, H. Veisi,
Appl. Organomet. Chem. 2015, 29, 195. (b) R. Ghorbani‐Vaghei,
S. Hemmati, H. Veisi, J. Mol. Catal. A: Chem. 2014, 393, 240. (c)
R. Ghorbani‐Vaghei, R. Karimi‐Nami, Z. Toghraei‐Semiromi,
M. Amiri, M. Ghavidel, Tetrahedron 2011, 67, 1930. (d) R.
Ghorbani‐Vaghei, Y. Maghbooli, Synthesis 2016, 48, 3803. (e)
R. Ghorbani‐Vaghei, Y. Maghbooli, A. Shahriari, J. Mahmoodi,
Mol. Diversity 2016, 20, 907. (f) R. Ghorbani‐Vaghei, S. M.
Malaekehpoor, Synthesis 2017, 49, 763. (g) R. Ghorbani‐Vaghei,
H. Veisi, H. Keypour, A. A. Dehghani‐Firouzabadi, Mol.
Diversity 2010, 14, 87. (h) H. Veisi, R. Ghorbani‐Vaghei, S.
Hemmati, M. H. Aliani, T. Ozturk, Appl. Organomet. Chem.
2015, 29, 26.
REFERENCES
[1] S. Zhang, X. Zhao, H. Niu, Y. Shi, Y. Cai, G. Jiang, J. Hazard.
Mater. 2009, 167, 560.
[2] (a) G. Ouyang, P. Zhang, G. Xu, B. Song, S. Yang, L. Jin, W.
Xue, D. Hu, P. Lu, Z. Chen, Molecules 2006, 11, 383. (b) R.
Rohini, K. Shanker, P. M. Reddy, Y. P. Ho, V. Ravinder, Eur.
J. Med. Chem. 2009, 44, 3330. (c) S. Yang, Z. Li, L. Jin, B. Song,
G. Liu, J. Chen, Z. Chen, D. Hu, W. Xue, R. Xu, Bioorg. Med.
Chem. Lett. 2007, 17, 2193. (d) G. F. Xu, B. A. Song, P. S.
Bhadury, S. Yang, P. Q. Zhang, L. H. Jin, W. Xue, D. Y. Hu,
P. Lu, Bioorg. Med. Chem. 2007, 15, 3768. (e) L. Y. Zeng, C.
Cai, J. Comb. Chem. 2010, 12, 35.
[3] M. D. Mashkovskii, Lekarstvennye sredstva (Drugs), Novaya
Volna, Moscow 2010.
SUPPORTING INFORMATION
[4] Y. W. Lam, M. H. Duroux, J. G. Gambertoglio, S. L. Barriere, B.
Additional Supporting Information may be found online
in the supporting information tab for this article.
J. Guglielmo, Anti microb. Agents Chemother 1988, 32, 298.
[5] G. Michel, J. Bergeron, L. John, Anti microb. Agent Chemother.
1973, 396.
[6] M. S. Zhidovinova, G. L. Rusinov, I. G. Ovchinnikova, Russ.
Chem. Bull. 2003, 52, 1768.
How to cite this article: Ghorbani‐Vaghei R,
Alavinia S, Sarmast N. Fe3O4@SiO2@propyl‐
ANDSA: A new catalyst for the synthesis of
tetrazoloquinazolines. Appl Organometal Chem.
2017;e4038. https://doi.org/10.1002/aoc.4038
[7] V. L. Gein, E. P. Tsyplyakova, E. A. Rozova, L. F. Gein, Russ. J.
Org. Chem. 2003, 39, 753.
[8] V. L. Gein, I. N. Vladimirov, A. A. Kurbatova, N. V. Nosova, I.
V. Krylova, M. I. Vakhrin, O. V. Fedorova, Russ. J. Org. Chem.
2010, 46, 699.