Efficient three-component synthesis of 4-aminoquinazolines

Article abstract of DOI:10.1080/00397910903019967

4-Aminoquinazolines were synthesized in good yields via a one-pot, three-component reaction of anthranilonitrile, acylchlorides, and ammonium acetate in the presence of catalytic amounts silica-supported Preyssler nanoparticles under refluxing conditions.

Full text of DOI:10.1080/00397910903019967

This article was downloaded by: [University of Edinburgh]
On: 08 June 2012, At: 09:48
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Efficient Three-Component Synthesis of
4-Aminoquinazolines
Majid M. Heravi a , Samaheh Sadjadi a , Negar Mokhtari Haj a ,
Hossein A. Oskooie a & Fatemeh F. Bamoharram b
a Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
b Department of Chemistry, School of Sciences, Islamic Azad
University, Mashhad Branch, Mashhad, Iran
Available online: 22 Feb 2010
To cite this article: Majid M. Heravi, Samaheh Sadjadi, Negar Mokhtari Haj, Hossein A. Oskooie
& Fatemeh F. Bamoharram (2010): Efficient Three-Component Synthesis of 4-Aminoquinazolines,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:6, 861-867
To link to this article: http://dx.doi.org/10.1080/00397910903019967
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 40: 861–867, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903019967
EFFICIENT THREE-COMPONENT SYNTHESIS OF
4-AMINOQUINAZOLINES
Majid M. Heravi,1 Samaheh Sadjadi,1 Negar Mokhtari Haj,1
Hossein A. Oskooie,1 and Fatemeh F. Bamoharram2
1Department of Chemistry, School of Sciences, Azzahra University, Vanak,
Tehran, Iran
2Department of Chemistry, School of Sciences, Islamic Azad University,
Mashhad Branch, Mashhad, Iran
4-Aminoquinazolines were synthesized in good yields via a one-pot, three-component
reaction of anthranilonitrile, acylchlorides, and ammonium acetate in the presence of
catalytic amounts silica-supported Preyssler nanoparticles under refluxing conditions.
Keywords: 4-Aminoquinazolines; heteropolyacids; recyclable catalyst
INTRODUCTION
Heteropoly acids (HPAs) are well-defined molecular clusters that are remark-
able for their molecular and electronic structural diversity, and they are significant in
many areas (e.g., catalysis, medicine, and materials science).[1–2]
The application of HPAs as catalytic materials is growing continuously in the
catalytic field. These compounds possess unique properties such as Bro¨nsted acidity,
the possibility of modifying their acid–base and redox properties by changing their
chemical composition (substituted HPAs), the ability to accept and release electrons,
high proton mobility, easy workup procedures, easy filtration, and minimal cost and
waste generation because they can be recycled.[3–7]
Over the past decade, because of the unique properties of nano particles along
with their novel properties and potential applications in different fields,[8] synthesis
and characterization of catalysts with smaller dimensions have been become the
most interesting topic of research. As the particle size decreases, the relative number
of surface atoms increases, and thus activity increases. Moreover, because of quan-
tum size effects, nanometer-sized particles may exhibit unique properties for a wide
range of applications.[9]
In our attempt to use HPAs as catalysts in organic reactions, we reported that
the Preyssler HPA, H14[NaP5W30O110], shows strong catalytic characterization.[10]
Received April 12, 2009.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Sciences,
Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
861

862
M. M. HERAVI ET AL.
We decided to immobilize H14[NaP5W30O110] on SiO2 nanoparticles and investigate
the catalytic behavior of this new catalyst.
Quinazolines are classes of fused heterocycles that are of considerable interest
because of the diverse range of their biological properties (e.g., anticancer, diuretic,
anti-inflammatory, anticonvulsant, and antihypertensive activities.[11,12]
One of the most important quinazoline derivatives is 4-aminoquinazoline.
4-Aminoquinazolines can be used as fungicides[13] and anti-inflammatory,[14]
anticancer,[15] antimicrobial, and antihypertensive agents.[16]
4-Aminoquinazolines have not been the object of new synthetic developments in
the past few years, and most reports on their preparation use only classical methods.[17]
The most recent report for synthesis of 4-aminoquinazolines was reaction of
cyanoaromatic compounds with anthranilonitrile using basic catalyst under
microwave irradiation.[18]
Although this reaction is an efficient method, there is a limitation for basic
catalyst. t-BuOK was the best catalyst, and other bases such as NaH, MeONa,
and lithium bis(trimethylsilyl)amide were unsuitable for this reaction. In classical
reflux condition, this reaction is not efficient for preparation of 4-aminoquinazolines.
Recently, we reported the successful application of (H14[NaP5W30O110])=SiO2
as catalyst in an organic reaction.[19]
Considering the poor yields of some classical methods for synthesis of
4-aminoquinazolines and lack of investigation of the synthesis of these compounds
in recent years, herein we report synthesis of 4-aminoquinazolines from a one-pot
reaction of 2-amino benzonitrile, acylchloride, and ammonium acetate in the pres-
ence of catalytic amounts of silica-supported Preyssler nanoparticles (Scheme 1).
The results of the synthesis of 4-aminoquinazolines are summarized in Table 1.
As shown in this table, the yields of reactions are good to excellent.
In the case of benzoyl chloride derivatives, it is observed that the electron-
withdrawing group on the benzoyl chlorides can increase the yields of reactions.
The plausible mechanism is shown in Scheme 2. To establish our proposed
mechanism, the reaction of anthranilonitrile and acylchlorides in the presence of
heteropolyacid was done, and A was detected as the only product. Adding
ammonium acetate to the mixture of A and a catalytic amount of heteropolyacid
led to formation of 4-aminoquinazolines.
To show the role of catalyst, the reactions were performed in the absence of the
catalyst. The results showed that 4-aminoquinazolines were not achieved without
using (H14[NaP5W30O110])=SiO2.
To compare the efficiency of (H14[NaP5W30O110])=SiO2 and H14[NaP5W30
O110], the reactions have been carried out in the presence of both catalysts in the
same reaction conditions. The results are summarized in Table 2.
Scheme 1. Synthesis of 4-aminoquinazolines in the presence of silica-supported Preyssler nanoparticles.

SYNTHESIS OF AMINOQUINAZOLINES
863
Table 1. Synthesis of 4-aminoquinazolines using (H14[NaP5W30O110])=SiO2 under
refluxing conditions
Entry
R
Product
Yield (%)a
1
CH3
95
2
3
4
ph
93
89
88
4-OMe ph
4-Me ph
5
6
4-Cl ph
92
90
4-NO2 ph
7
2-NO2 ph
90
aYields refer to isolated products.
To optimize the amount of catalyst, the synthesis of two 4-aminoquinazolines
using various amounts of catalysts (0.1, 0.3, 0.5 mol%) were carried out. The results
for synthesis of 4-aminoquinazolines from reaction of 2-amino benzonitrile, acyl-
chloride, and ammonium acetate using different amounts of (H14[NaP5W30O110])=
SiO2 are shown in Table 3. It is clear from this table that the yields of reactions in
very small amounts of catalysts are high, and the optimum amount of catalyst
was selected as 0.3 mol% for all derivatives.

864
M. M. HERAVI ET AL.
Scheme 2. The plausible mechanism of the synthesis of 4-aminoquinazolines.
In summary, 4-aminoquinazolines were synthesized in good yields via a
one-pot, three-component reaction of anthranilonitrile, acylchlorides, and ammo-
nium acetate in the presence of catalytic amounts of (H14[NaP5W30O110])=SiO2
under refluxing conditions.
EXPERIMENTAL
All the chemicals were purchased from Merck Company. (H14[NaP5W30O110])=
SiO2 was prepared according to our previous work.[19] Melting points were
measured using an Barnstead Electro Thermal instrument. Gas chromatography
(GC)=mass analysis was performed using Agilent 6890 GC system Hp-5 capillary
30 m  530 mm  1.5 mm nominal. All compounds were known. Their physical
data were compared with those of authentic compounds and found to be
identical.
Table 2. Comparison of efficiency of (H14[NaP5W30O110])=SiO2 and H14[NaP5W30O110] in
the synthesis of 4-aminoquinazoline derivatives
Entry
R
Catalyst
Yield (%)a
1
2
CH3
CH3
(H14[NaP5W30O110])=SiO2
95
90
93
88
89
82
88
81
92
87
90
85
90
85
H14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
H14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
H14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
H14[NaP5W30O110
(H14[NaP5W30O110])=SiO2
H14[NaP5W30O110
]
3
ph
ph
4
H
]
5
4-OMe ph
4-OMe ph
4-Me ph
4-Me ph
4-Cl ph
4-Cl ph
4-NO2 ph
4-NO2 ph
2-NO2 ph
2-NO2 ph
6
]
7
8
H
]
9
10
11
12
13
14
]
]
]
aYields refer to isolated products.

SYNTHESIS OF AMINOQUINAZOLINES
865
Table 3. Results of using different amounts of (H14[NaP5W30O110])=SiO2 on
yields of 4-aminoquinazolines
Entry
R
Catalyst amount (mol%)
Yield (%)a
1
2
3
4
5
6
CH3
CH3
CH3
ph
0.1
0.3
0.5
0.1
0.3
0.5
91
95
95
90
93
93
ph
ph
aYields refer to isolated products.
Synthesis of 4-Aminoquinazolines
A catalytic amount of (H14[NaP5W30O110])=SiO2 (0.3 mol%) was added to a
mixture of 2-amino benzonitrile (10 mmol), acylchloride (10 mmol), and ammonium
acetate (10 mmol), and the mixture was refluxed in acetonitrile (10 mL) for 1 h. The
progress of the reaction was monitored by thin-layer chromatography (TLC). At the
end of the reaction, the catalyst was filtered off, the solvent was evaporated, and
products were recrystallized from an ethanol mixture.
All products were identified by comparison of their physical and spectroscopic
data with those reported for authentic samples.[18,20]
Recycling of the Catalyst
At the end of the reaction, the catalyst could be recovered by simple filtration.
The recycled catalyst could be washed with dichloromethane and subjected to a
second run of the reaction process. To ensure that the catalyst did not dissolve in
the solvent, the filtered catalysts were weighted before reuse. The results show that
this catalyst is not soluble in the solvent. In Table 4, the comparison of efficiency
of this catalyst in synthesis of 4-aminoquinazolines after three times is reported.
As is shown, the yields of reactions after using this catalyst three times show a slight
reduction.
Table 4. Comparison of efficiency of (H14[NaP5W30O110])=SiO2 in synthesis of
4-aminoquinazolines after three runs
Yield (%)a
Entry
R
First run
Second run
Third run
1
2
3
4
5
6
7
CH3
ph
95
93
89
88
92
90
90
94
93.5
92
92.5
88
4-OMe ph
4-Me ph
4-Cl ph
4-NO2 ph
2-NO2 ph
87
87.2
91
86.3
90
89
89
88.3
88
aYields refer to isolated products.

866
M. M. HERAVI ET AL.
ACKNOWLEDGMENT
M. M. H. is thankful to the Iran National Science Foundation for partial
financial support.
REFERENCES
1. Misono, M.; Ono, L.; Koyano, G.; Aoshima, A. Heteropolyacids versatile green catalysts
usable in a variety of reaction media. Pure Appl. Chem. 2000, 72, 1305.
2. Pope, M. T.; Muller, A. Polyoxometalates: From Platonic Solids to Anti-Retroviral
Activity; Kluwer Academic Publishers: Dordrecht, Netherlands, 1994.
3. Heravi, M. M.; Rajabzadeh, G.; Bamoharram, F. F.; Seifi, N. An eco-friendly catalytic
route for synthesis of 4-amino-pyrazolo[3,4-d]pyrimidine derivatives by Keggin heteropo-
lyacids under classical heating and microwave irradiation. J. Mol. Catal. A: Chem. 2006,
256, 238.
4. Heravi, M. M.; Bakhtiari, K.; Bamoharram, F. F. An efficient and chemoselective
synthesis of acylals from aromatic aldehydes and their regeneration, catalyzed by
12-molybdophosphoric acid. Catal. Commun. 2006, 7, 499.
5. Heravi, M. M.; Bamoharram, F. F.; Rajabzadeh, G.; Seifi, N.; Khatami, M. Preyssler
heteropolyacid [NaP5W30O110]
14À, as a new, green and recyclable catalyst for the synthesis
of [1,2,4]triazino[4,3-b][1,2,4,5]tetrazines. J. Mol. Catal. A: Chem. 2006, 259, 213.
6. Pope, M. T. Heteropoly and Isopoly Oxometalates; Springer: Berlin, 1983.
7. Heravi, M. M.; Bakhtiari, K.; Bamoharram, F. F. 12-Molybdophosphoric acid: A recycl-
able catalyst for the synthesis of Biginelli-type 3,4-dihydropyrimidine-2(1H)-ones. Catal.
Commun. 2006, 7, 373.
8. Gorla, C. R.; Emanetoglu, N. W.; Liang, S.; Mago, W. E.; Lu, Y.; Wraback, M.; Shen, H.
Structural, optical, and surface acoustic wave properties of epitaxial ZnO films grown
on (0112) sapphire by metalorganic chemical vapor deposition. J. Appl. Phys. 1999,
85, 2595.
9. Zheng, J.; Zhang, C.; Dickson, R. M. Highly fluorescent, water-soluble, size-tunable gold
quantum dots. Phys. Rev. Lett. 2004, 93, 077402.
10. Heravi, M. M.; Sajadi, S.; Oskooie, H. A.; Hekmat Shoar, R.; Bamoharram, F. F. Hetero-
polyacids as heterogeneous and recyclable catalysts for the synthesis of benzimidazoles.
Catal. Commun. 2008, 9, 504.
11. Chan, J. H.; Hong, J. S.; Kuyper, L. F.; Jones, M. L.; Baccanari, D. P.; Tansik, R. L.;
Boytos, C. M.; Rudolph, S. K.; Brown, A. D. Synthesis of 1,3-diamino-7,8,9,10-tetrahy-
dropyrido[3,2-f]quinazolines: Inhibitors of candida albicans: Dihydrofolate reductase as
potential antifungal agents. J. Heterocycl. Chem. 1997, 34, 145.
12. Dempcy, R. O.; Skibo, E. B. Rational design of quinazoline-based irreversible
inhibitors of human erythrocyte purine nucleoside phosphorylase. Biochemistry 1991,
30, 8480.
13. Haley, G. J. Substituted quinazoline fungicidal agents. US Patent 5373011, 1994.
14. Palanki, M. S. S.; Suto, M. J. Quinazoline analogs and related compounds and methods
for treating inflammatory conditions. US Patent 5939421, 1999.
15. Barker, A. J. Quinazoline derivatives. US Patent 5942514, 1999, and 5932574, 1999.
16. Nauta, W. T. 4-Amino-pyrimidine derivatives. US Patent 3980650, 1976.
17. Katrizky, A. R.; Rees, C. W. (Eds.). Comprehensive Heterocyclic Chemistry II; Pergamon
Press: Oxford, 1996.
´
18. Seijas, J. A.; Vazquez-Tato, M. P.; Martınez, M. M. Microwave-enhanced synthesis of
4-aminoquinazolines. Tetrahedron Lett. 2000, 41, 2215.

SYNTHESIS OF AMINOQUINAZOLINES
867
19. Heravi, M. M.; Sadjadi, S.; Sadjadi, S.; Oskooie, H. A.; Hekmatshoar, R.; Bamoharram,
F. F. Silica-supported Preyssler nanoparticles as new catalysts in the synthesis of
4(3H)-quinazolinones. S. Afr. J. Chem. 2009, 62, 1.
20. Foster, C. H.; Elam, E. U. Novel one-pot synthesis of 4-aminoquinazolines. J. Org. Chem.
1976, 41, 2646.