Dawson heteropolyacid: A green, eco-friendly, and reusable catalyst for one-pot synthesis of 4-aminoquinazolines

Article abstract of DOI:10.1080/15533174.2012.741181

A new multicomponent synthesis of 4-aminoquinazolines from the reaction of anthranilonitrile, acylchlorides, and ammonium acetate in the presence of catalytic amounts of Dawson-type heteropolyacids (HPAs) is reported. The catalytic performance of different forms of Dawson-type HPAs, H₆ P₂M₁₈O6₂ (M = W^VI, Mo^VI) and mixed addenda forms (M = Co^II, Cu^II, Ni^II, Mn^III) were compared and in all cases, maximum of yield was observed by using H₆P₂W₁₈O6₂ as catalyst. The plausible mechanism was estimated. In all cases, the Dawson catalyst was easily recovered and recycled with retention of their initial structure and activity. The effects of reaction conditions have been studied and the results showed yields of reaction are good to excellent. Copyright Taylor and Francis Group, LLC.

Full text of DOI:10.1080/15533174.2012.741181

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Synthesis and Reactivity in Inorganic, Metal-Organic,
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Dawson Heteropolyacid: A Green, Eco-Friendly,
and Reusable Catalyst for One-Pot Synthesis of 4-
Aminoquinazolines
Fatemeh F. Bamoharram a , Majid M. Heravi b , Mina Roshani a & Katayon Kosari a
a Department of Chemistry, Mashhad Branch , Islamic Azad University , Mashhad , I. R. Iran
b Department of Chemistry, School of Science , Alzahra University , Vank , Tehran , I. R. Iran
Accepted author version posted online: 04 Dec 2012.Published online: 07 Mar 2013.
To cite this article: Fatemeh F. Bamoharram , Majid M. Heravi , Mina Roshani & Katayon Kosari (2013) Dawson
Heteropolyacid: A Green, Eco-Friendly, and Reusable Catalyst for One-Pot Synthesis of 4-Aminoquinazolines, Synthesis and
Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 43:5, 539-542, DOI: 10.1080/15533174.2012.741181
To link to this article: http://dx.doi.org/10.1080/15533174.2012.741181
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 43:539–542, 2013
Copyright ꢀ Taylor & Francis Group, LLC
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ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2012.741181
Dawson Heteropolyacid: A Green, Eco-Friendly, and
Reusable Catalyst for One-Pot Synthesis of
4-Aminoquinazolines
Fatemeh F. Bamoharram,1 Majid M. Heravi,2 Mina Roshani,1
and Katayon Kosari1
1Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I. R. Iran
2Department of Chemistry, School of Science, Alzahra University, Vank, Tehran, I. R. Iran
subclass of tandem reaction,[5] are one-pot processes in which
A new multicomponent synthesis of 4-aminoquinazolines from
the reaction of anthranilonitrile, acylchlorides, and ammonium
acetate in the presence of catalytic amounts of Dawson-type het-
eropolyacids (HPAs) is reported. The catalytic performance of dif-
ferent forms of Dawson-type HPAs, H6 P2M18O62 (M = WVI, MoVI)
and mixed addenda forms (M = CoII, CuII, NiII, MnIII) were com-
pared and in all cases, maximum of yield was observed by using
H6P2W18O62 as catalyst. The plausible mechanism was estimated.
In all cases, the Dawson catalyst was easily recovered and recycled
with retention of their initial structure and activity. The effects of
reaction conditions have been studied and the results showed yields
of reaction are good to excellent.
several easily accessible components react to form a single
product.[6]
In particular, MCRs that provide heterocyclic compounds
in a single operation are of enormous importance in synthetic
organic and medicinal chemistry.[7]
Among heterocyclic compounds, 4-aminoquinazoline and its
derivatives are useful as fungicides and as anti-inflammatory, an-
timicrobial, and antihypertensive agents.[8–11] In particular, they
are potent and highly selective inhibitors of tyrosine kinase.[12]
Therefore, in recent years, the synthesis of 4-aminoquinazolines
has attracted much attention.[13] Traditional preparation of 4-
aminoquinazolines involves the reaction of amines and 4-
chloroquinazolines. Also, the most recent report for synthesis
of 4-aminoquinazolines was reaction of cyanoaromatic com-
pounds with anthranilonitrile using catalyst under microwave
irradiation.[11] 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 prepa-
ration of 4-aminoquinazolines.
In the other process, 4-aminoquinazoline derivatives can be
obtained by the steps of reacting quinazolin-4-one or its deriva-
tives with a chlorinating agent in a first organic solvent in the
presence of an organic base, and subsequently reacting the re-
action product with an amine compound represented by the
formula R5-NH-R6 (R5 and R6 represent hydrogen or an op-
tionally substituted hydrocarboxyl group) in the presence of a
second organic solvent.
Keywords 4-aminoquinazolines, Dawson, heteropolyacids, recy-
clable catalyst
INTRODUCTION
In view of green chemistry, the substitution of harmful liquid
acids by solid reusable heteropolyacids (HPAs) as catalyst in
organic synthesis is the most promising application of these
acids.[1,2]
Thus the development of methods using HPAs as catalysts
for the synthesis of fine chemicals, such as flavors and
pharmaceuticals, and in food industries, has gained attention
in the last decade.[3] Catalysts based on HPAs have many
advantages over liquid-acid catalysts. They are not corrosive
and are environmentally benign and present fewer disposal
problems. Solid HPAs are important in organic synthesis owing
to easy work-up procedures, easy filtration, and reduction of
cost and waste generation through reuse and recycling of the
catalysts.[4] One of the most important types of organic reactions
is a multicomponent reaction (MCR). MCRs, an important
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-aminobenzonitrile, acylchloride, and ammonium acetate in
the presence of catalytic amounts of Dawson-type HPAs, H6
P2M18O62 (M = WVI, MoVI) and mixed addenda forms (M =
CoII, CuII, NiII, MnIII; Scheme 1).
Received 3 November 2011; accepted 15 October 2012.
Address correspondence to Fatemeh F. Bamoharram, Department
of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, I.
R. Iran. E-mail: fbamoharram@mshdiau.ac.ir
539

540
F. F. BAMOHARRAM ET AL.
TABLE 2
Synthesis of 4-aminoquinazolines using H6P2W18O62
under refluxing conditions
Yield%a
73.8
Product
R
Entry
1
SCH. 1. Synthesis of 4-aminoquinazolines in the presence of Dawson-type
heteropolyacids.
CH3
EXPERIMENTAL
Chemicals and Instruments
71.1
67
Ph
2
3
All of the chemicals were commercially available. Daw-
son HPAs have been prepared according to the literature.[14]
IR spectra were obtained with a Bruker 500 scientific
spectrometer (USA).
General Procedure for the Synthesis of
4-Aminoquinazolines
4-OMe ph
To a mixture of 2-aminobenzonitrile (10 mmol), acylchlo-
ride (10 mmol), and ammonium acetate (10 mmol) catalytic
amount of Dawson type of HPAs was added and the mixture
was heated and refluxed in acetonitrile for 1 h. The progress
of the reaction was monitored by TLC. On completion, the
catalyst was filtered off, the solvent was evaporated and the
all products were identified by comparison of their physical
and spectroscopic data with those reported for the authentic
samples.[15,16]
66
4-Me ph
4
Recyclability of the Catalyst
At the end of the reaction, the catalyst could be recovered
by a simple filtration. The recycled catalyst was washed with
dichloromethane and used in a second run of the reaction pro-
cess. To confirm that the catalyst was not soluble in the reaction
70
68
65
4-Cl ph
4-NO2 ph
2-OMe ph
5
6
7
TABLE 1
Comparison of efficiency of H6P2W18O62 in synthesis of
4-aminoquinazolines after three runs
Yield (%)a/run
Entry
R
First
Second
Third
1
2
3
4
5
6
7
CH3
Ph
73.8
71.1
67
66
70
73
70
64
62
70
63
64
72
69
63
61
69
62
63
4-OMe ph
4-Me ph
4-Cl ph
4-NO2 ph
2-OMe ph
68
65
aYield refers to isolated products from the reaction 2-
aminobenzonitrile (10 mmol), acylchloride (10 mmol), and am-
monium acetate (10 mmol) in the presence of [H6P2W18O62]
(0.03 mmol) under refluxing conditions in CH3CN.
aYield refers to isolated products from the reaction 2-
aminobenzonitrile (10 mmol), acylchloride (10 mmol), and ammonium
acetate (10 mmol), in the presence of [H6P2W18O62] (0.03 mmol) under
refluxing conditions in CH3CN.

CATALYTIC SYNTHESIS OF 4-AMINOQUINAZOLINES
541
SCH. 2. The plausible mechanism of the synthesis of 4-aminoquinazolines.
TABLE 4
solvent, the filtered catalyst was weighted before reuse. The re-
sults indicated that the catalysts were not soluble in the solvent,
and the yields of reactions using these catalysts over three runs
indicated only a slight loss of activity (Table 1).
The results of using different amounts of Dawson-type
heteropolyacid on yields of 4-aminoquinazolines
Yield (%)a
Catalyst amount (mol%)
R
Entry
70
73.8
73.8
0.1
0.3
0.5
CH3
CH3
CH3
1
2
3
RESULTS AND DISCUSSION
Recently, we reported the successful application of HPAs
as green and reusable catalysts in MCRs for the synthesis of
heterocyclic compounds.[16] In our attempt to use HPAs as cat-
alysts in organic reactions, herein we report that the Dawson-
type HPAs show strong catalytic activity for synthesis of 4-
aminoquinazolines. The reaction conditions (solvent, catalyst
type, and catalytic amount) were studied to optimize this proce-
dure. The results on the synthesis of 4-aminoquinazolines from
the reaction of 2-aminobenzonitrile, acylchloride, and ammo-
nium acetate using H6P2W18O62 are summarized in Table 2. As
shown in this table, the yields of reactions are good to excellent.
Benzoyl chloride derivatives with electron-withdrawing group
gave slightly better yields than benzoyl chloride with electron-
donating groups.
The plausible mechanism is shown in Scheme 2. To establish
our proposed mechanism, the reaction of anthranilonitrile and
acylchlorides in the presence of HPA was done, and A was
detected as the only product. Adding ammonium acetate to the
mixture of A and a catalytic amount of HPA led to formation of
4-aminoquinazolines.
aYield refers to isolated products from the reaction 2-
aminobenzonitrile (10 mmol), acylchloride (10 mmol), and ammonium
acetate (10 mmol) in the presence of various amounts of [H6P2W18O62]
under refluxing condition in CH3CN.
The effect of solvent on the synthesis of 4-aminoquinazolines
showed that solvents including CH3CN, CHCl3, C2H5OH, and
DMF can be the best in terms of yields (Table 3).
To optimize the amount of catalyst, the yields of reaction us-
ing various amounts of catalysts (0.1, 0.3, and 0.5 mol%) were
TABLE 5
Effect of various Dawson-type heteropolyacids on yields of
4-aminoquinzolines
Entry
R
Catalyst
Yield (%)a
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
CH3
CH3
CH3
Ph
H6P2W18O62
H6P2Mo18O62
Na6P2Mo18O62
73.8
72
50.1
40
K6P2W17O61(Mn+3.OH2)
K8P2W17O61(Co+2.OH2)
K8P2W17O61(Ni+2.OH2)
K8P2W17O61(Cu+2.OH2)
H6P2W18O62
38
37
TABLE 3
Effect of varying the solvent on the yield of
4-aminoquinazolines
36.2
70.1
69
Yield(%)a
catalyst
Solvent
R
Entry
9
Ph
H6P2Mo18O62
10
11
12
13
14
Ph
Ph
Ph
Ph
Na6P2Mo18O62
50.9
40.2
38.5
37
73.8
67
65
H6P2W18O62
H6P2W18O62
H6P2W18O62
H6P2W18O62
CH3CN
CHCl3
C2H5OH
DMF
CH3
CH3
CH3
CH3
1
2
3
4
K6P2W17O61(Mn+3.OH2)
K8P2W17O61(Co+2.OH2)
K8P2W17O61(Ni+2.OH2)
K8P2W17O61(Cu+2.OH2)
63
Ph
35
aYield refers to isolated products from the reaction 2-
aminobenzonitrile (10 mmol), acylchloride (10 mmol),. and ammo-
nium acetate (10 mmol) in the presence of [H6P2W18O62] (0.03 mmol)
under refluxing conditions.
aYield refers to isolated products from the reaction 2-
aminobenzonitrile (10 mmol), acylchloride (10 mmol), and ammo-
nium acetate (10 mmol) in the presence of various heteropolyacids
(0.03 mmol) under refluxing conditions in CH3CN.

542
F. F. BAMOHARRAM ET AL.
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CONCLUSIONS
In conclusion, we have reported a new catalytic method
for the synthesis of 4-aminoquinazolines from reaction of 2-
aminobenzonitrile, acylchloride, and ammonium acetate in the
presence of catalytic amounts of Dawson-type HPAs as efficient,
reusable, and eco-friendly heterogeneous inorganic catalysts.
The advantages of this method are the easy work-up procedure
and high yields of products.