CO2 involved synthesis of quinazoline-2,4(1 H,3 H)-diones in water using melamine as a thermoregulated catalyst

Article abstract of DOI:10.1139/cjc-2017-0705

In this study, pharmaceutically relevant quinazoline-2,4(1H,3H)-diones were synthesized eco-efficiently by cycloaddition of CO₂ and 2-aminobenzonitrile in water, catalyzed by melamine as a thermoregulated catalyst. Quinazoline-2,4(1H,3H)-dione was produced selectively with 92% yield at 120 °C, 4.2 MPa, and automatically separated from the hot catalytic aqueous solution, which was reused directly for several runs until its activity decreased in an obvious manner. Then, the catalyst melamine was recrystallized from the spent aqueous solution via simple cooling and reused for another several catalytic runs. The efficient valorization of CO₂ and the straightforward stepwise recovery of the products and catalyst were important to save energy and minimize process waste for the practical industrial production.

Full text of DOI:10.1139/cjc-2017-0705

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Canadian Journal of Chemistry
CO involved synthesis of quinazoline-2,4(1H,3H)-diones in water using
2
melamine as a thermoregulated catalyst
Guo-Ying Zhao, a* Ling-Ling Mu,a,b Latif Ullah,a Meng Wang,a Hong-Ping Li,b
Xin-Xin Guanb*
aBeijing Key Laboratory of Ionic Liquids Clean Process, State Key Laboratory of Multiphase
Complex Systems, Key Laboratory of Green Process and Engineering, Institute of Process
Engineering, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China
bCollege of Chemistry and Molecular Engineering Zhengzhou University No. 100 of Science
Road, Zhengzhou, Henan Province, 450001, P. R. China
a*Guoying Zhao; E-mail: gyzhao@ipe.ac.cn; Tel./ Fax: +86-10-82544875
b*Xin-Xin Guan; E-mail: guanxin@zzu.edu.cn;

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Canadian Journal of Chemistry
Abstract
In this study, pharmaceutically relevant quinazoline-2,4(1H,3H)-diones were synthesized
eco-efficiently by cycloaddition of CO and 2-aminobenzonitrile in water, catalyzed by
2
melamine as a thermoregulated catalyst. Quinazoline-2,4(1H,3H)-dione was produced
selectively with 92% yield at 120 ºC, 4.2 MPa and automatically separated from the hot
catalytic aqueous solution, which was reused directly for several runs until its activity
decreased in an obvious manner. Then the catalyst melamine was recrystallized from the
spent aqueous solution via simple cooling and reused for another several catalytic runs. The
efficient valorization of CO , and the straightforward stepwise recovery of the products and
2
catalyst, was important to save energy and minimize process waste for the practical industrial
production.
Keywords: Quinazoline-2,4(1H,3H)-diones; Carbon dioxide; Water;
Thermoregulated
catalyst; Cycloaddition
1
. Introduction
Despite of its notorious greenhouse effect, CO is a nontoxic, abundant and renewable
2
C1 resource. The valorization of CO could be one of the effective strategies to recycle
2
exhaust CO and therefore reduce its emission and consequently its impact on climate change.
2
Up to now, a variety of value-added chemicals including carbonates,1-3 ureas,4-6 organic
carboxylic acid,7-10 alcohols, and fuels,
11
12-13
etc., have been produced with CO as feedstock.
2
In particular, the cycloaddition of CO2 and 2-aminobenzonitriles to prepare

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quinazoline-2,4(1H,3H)-dione and its derivatives have recently gotten attention because of
their wide relevance to pharmaceutical companies (Scheme 1).14-16 Various catalytic processes
have been developed for this chemistry including heterogeneous catalysis with organic
solvents,17-18 homogeneous catalysis with aqueous solution,16 solvent-free14-15 and even
1
9
catalyst-free protocols. Nevertheless, the development of a smart and clean catalytic process,
which permits an efficient and selective homogeneous conversion, the self-separation of
product and catalyst as well as near zero waste emission, is challenging.
Scheme 1 The cycloaddition of CO and 2-aminobenzonitrile for the synthesis of
2
quinazoline-2,4(1H,3H)-dione.
Atom/step economy and the environmental factor (E factor) are two metrics to guide the
2
0
design of a green and clean process. The appropriate selection of solvent is one of the main
priorities to improve the step economy and E factor of the process as solvents constitute
almost 60% of all industrial emissions worldwide.20-21 Among various benign solvents, water
is the first choice in view of its price, safety, availability and environmental friendliness. It
has also been used as an effective reaction media for the cycloaddition of 2-aminobenzonitrile
with CO2.16, 19 In their studies, the product quinazoline-2,4(1H,3H)-diones proved that it can
be automatically separated from water, which avoids consuming large quantities of energy
and solvents typically required by traditional product separation in many manufacturing

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processes.22-23 However, strict reaction conditions (pressure up to 14 MPa) were required
1
9
without any catalyst. And with choline hydroxide aqueous solution of 20 wt% as catalytic
reaction medium, the recycling of choline hydroxide was difficult and its cycle-stability is
1
6
questionable. Water-based and thermomorphic catalytic systems could provide an elegant
approach for performing homogeneous reactions, facilitating the product separation and
catalyst recovery, and minimizing waste emission. Nevertheless, such smart processes have
not yet been reported for the synthesis of quinazoline-2,4(1H,3H)-diones using carbon
dioxide as a substrate.
We hereby describe a smart aqueous thermomorphic catalytic process for the synthesis
of quinazoline-2,4(1H,3H)-dione and related compounds. An organic catalyst -melamine- was
selected after screening as an efficient, thermoregulated and recyclable catalyst. The
cycloaddition of CO into quinazoline-2,4(1H,3H)-dione ran successfully at a temperature of
2
1
20 ºC where melamine, 2-aminobenzonitrile, and water formed a homogenous solution.
After reaction, the products were filtered out at a temperature of 60 ºC, and the hot and
aqueous solution of melamine was reused for the next catalytic run. The use of a catalyst
avoided sharp fluctuations in the temperature during the cycles and saved valuable energy by
using the hot product separation approach. After several catalytic cycles, the catalytic activity
of melamine-based aqueous solution was reduced because of impurities accumulation. The
used melamine was recrystallized from aqueous solution by cooling, and was reused for next
catalytic runs together with fresh water, which minimized waste emission during reaction
process.

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Canadian Journal of Chemistry
2
. Materials and methods
.1 Materials
CO was supplied by Beijing Analytical Instrument Factory with a purity of 99.99%.
2
2
2
-Aminobenzonitrile (1a) (purity >98%), 2-Amino-4,5-dimethoxybenzonitrile (2a)
>99%), 2-Amino-5-bromobenzonitrile (3a) (purity >99%),
-Amino-5-chlorobenzonitrile (4a) (purity >99%), 2-Amino-4-chlorobenzonitrile (5a)
(purity
2
(purity >98%), and 2-Amino-5-fluorobenzonitrile (6a) (purity >98%) were supplied by
Aladdin Industrial Corporation. The deuterated solvent (DMSO-d6) was obtained from
Cambridge Isotope Laboratories Corporation. The melamine, Cs CO , K CO , urea and other
2
3
2
3
chemicals were of analytical grade and purchased from Beijing HWRK Chem Co., LTD. All
the chemicals were used as received without further purification.
2
.2 Synthesis of quinazoline-2,4(1H,3H)-diones
A 25ml 316SS high-pressure reactor equipped with a magnetic stirrer was used for the
cycloaddition of CO and various aminobenzonitriles in this work. Typically, the reactor was
2
firstly loaded with 2-aminobenzonitrile (1a, 5 mmol), suitable amount of catalyst, water (5
mL), and was flushed with CO three times. Then the reaction system was heated up to the
2
desired temperature with stirring and charged with CO to the desired pressure. After the
2
reaction, the reactor was cooled down to 60 ºC in a constant-temperature bath and excess CO2
was released slowly. After filtered from the catalytic solution at 60 ºC, the product
quinazoline-2,4(1H,3H)-dione(1b) was subsequently washed with water (30 ml*2) and
tert-butyl methyl ether (20 ml*2), and dried overnight at 70 ºC. The mass of the product was

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determined by electronic balance (Mettler-Toledo) with an accuracy of 0.1 mg. For recycling
experiments, the remained catalytic solution was reused directly for next run, or cooled down
to room temperature to recycle the catalyst melamine by recrystallization. The recycled
melamine was dried overnight under vacuum at 70 ºC and used for next run.
For the cycloaddition of CO and other substrates (2a-6a), the procedure is similar. The
2
1
purity and structure of the products were characterized by NMR spectroscopy. H NMR and
13C NMR spectra were measured with a Bruker Avance Ⅲ (600 MHz) spectrometer with
DMSO-d6 as solvent. All the Characterization data of the products (2b–6b) are reported
below.
Quinazoline-2,4(1H,3H)-dione (1b): White solid, the optimized yield was 92% ( Table 2,
1
Entry1). H NMR (600 MHz, DMSO-d6) δ = 11.33 (s, 1H), 11.14 (s, 1H), 7.89 (d, J =7.4 Hz,
1
3
1
H), 7.64 (t, J=7.3 Hz, 1H), 7.20–7.04 (m, 2H). C NMR (151 MHz, DMSO-d6) δ= 162.84,
1
50.29, 140.82, 134.95, 126.92, 122.32, 115.29, 114.29. The NMR data for this compound
matched the reported data.14, 24
,7-Dimethoxyquinazoline-2,4(1H,3H)-dione (2b): White solid, the yield was 94%
Table 2, Entry 2). 1H NMR (600 MHz, DMSO-d6) δ = 11.16 (s, 1H), 10.93 (s, 1H), 7.26 (s,
6
(
1
3
1
1
H), 6.68 (s, 1H), 3.83 (s, 3H), 3.78 (s, 3H). C NMR (151 MHz, DMSO-d6) δ = 162.42,
54.89, 150.40, 145.00, 136.52, 107.14, 106.16, 97.75, 55.78, 55.68. The NMR data for this
compound matched the reported data.14, 24
6
-Bromoquinazoline-2,4(1H,3H)-dione (3b): Yellow solid, the yield was 88% ( Table 2,
1
Entry 3). H NMR (600 MHz, DMSO-d6) δ = 11.27 (s, 2H), 7.94 (s, 1H), 7.79 (d, J = 5.9 Hz,

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1
3
1
H), 7.12 (d, J = 6.5 Hz, 1H). C NMR (151 MHz, DMSO-d6) δ = 161.70, 150.01, 140.05,
1
37.49, 128.89, 117.75, 116.19, 113.80. The NMR data for this compound matched the
reported data.14, 24
-Chloroquinazoline-2,4(1H,3H)-dione (4b): Yellow solid, the yield was 90% ( Table 2,
6
1
Entry 4). H NMR (600 MHz, DMSO-d6) δ = 11.47 (s, 2H), 7.82 (s, 1H), 7.69 (s, 1H), 7.18 (d,
1
3
J = 8.2 Hz, 1H). C NMR (151 MHz, DMSO-d6) δ = 161.82, 150.02, 139.70, 134.80, 126.27,
1
25.89, 117.51, 115.76. The NMR data for this compound matched the reported data.24
7
-Chloroquinazoline-2,4(1H,3H)-dione (5b): Yellow solid, the yield was 82% ( Table 2,
1
Entry 5). H NMR (600 MHz, DMSO-d6) δ = 11.40 (s, 1H), 11.24 (s, 1H), 7.89 (d, J = 8.4 Hz,
1
3
1
1
H), 7.23–7.18 (m, 2H). C NMR (151 MHz, DMSO-d6) δ = 162.06, 150.14, 141.94, 139.25,
29.01, 122.46, 114.65, 113.30. The NMR data for this compound matched the reported data.
1
4, 24
6
-Fluoroquinazoline-2,4(1H,3H)-dione (6b).: White solid, the yield was 80% ( Table 2,
1
Entry 6). H NMR (600 MHz, DMSO-d6) δ = 11.43 (s, 2H), 7.60 (s, 1H), 7.57 (s, 1H), 7.16 (d,
1
3
J = 8.2 Hz, 1H). C NMR (151 MHz, DMSO-d6) δ = 162.10, 150.02, 137.53, 122.98, 122.82,
1
17.52, 115.39, 112.08. The NMR data for this compound matched the reported data.14, 24
3
. Result and discussion
3
.1 Thermomorphic catalysts screening
An efficient thermomorphic and aqueous reaction system offers an approach to perform
homogeneous catalysis at one temperature while facilitating biphasic separation of the
2
5
catalyst and products from water at another temperatures. With this in mind, we screened

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Canadian Journal of Chemistry
suitable,
thermoregulated
and recyclable catalysts for the
synthesis of
quinazoline-2,4(1H,3H)-dione (1b) via the cycloaddition of 2-aminobenzonitrile (1a) and CO2.
Due to its intrinsic weak basicity, the activation of 1a typically needs a basic or acidic catalyst.
Strong bases including TMG, DBU, [Bmim]OH etc. or acid catalysts are readily miscible
because of their high polarities or the formation of hydrogen bonds with water. Therefore, a
catalyst with medium basicity will be the choice for the thermomorphic and aqueous reaction
system. Melamine with pK =8 became one of the catalysts to test. In addition, melamine
a
exhibits a solubility that is temperature dependent, the aqueous solubility of which is shown
2
6
in Fig.1 using the experimental data(EXP) and calculated data(pH=7, pH=6, and pH=5)
according to the reported equation in the study of Xu.27
Fig. 1 The solubility of melamine in water at varied temperatures and pH.26-27
Firstly, we tested the catalytic activity of melamine and some other catalysts for the
synthesis of quinazoline-2,4(1H,3H)-dione(1b). The reaction results are shown in Table 1 for
water and DMF as solvents. In the first several trials, DMF was used as the solvent because of

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its high solubility for both the reported catalysts and CO . And the yield of product(1b)
2
reached a value up to 73% at 1 MPa of CO and 100 ºC. While using water as solvent, a lot of
2
1
b was still produced at the same reaction condition. 1b exhibits negligible solubility even in
hot water, which facilitates its separation. Upon increasing the reaction temperature and
pressure, the aqueous melamine solution efficiently catalyzed the conversion of
2
-aminobenzonitrile into 1b with excellent yield up to 92% at 120 ºC, 4.2 MPa(Entry6),
which was far better than other catalysts including potassium carbonate, and cesium
carbonate(entry 7-9).
Table 1
Entry
Catalysts screening for the synthesis of quinazoline-2,4(1H,3H)-dione
Catalyst
Solvent
T
Yield
(wt%)b
2
(
ºC)
25
85
1
2
3
4
5
6
7
8
9
C N (NH )
2 3
aDMF
aDMF
aDMF
awater
water
water
water
water
water
3
3
C N (NH )
2 3
59
3
3
C N (NH )
2 3
100
100
100
120
120
120
120
73
3
3
C N (NH )
2 3
28
3
3
C N (NH )
2 3
75
3
3
C N (NH )
2 3
92
3
3
CN H O
5
2
4
K CO
40
2
3
Cs CO
56
2
3

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Reaction condition: 2-aminobenzonitrile (5 mmol), water (5 mL), catalyst (63 mg, 10 mol%), CO (4.2
2
a
b
MPa), 18 h at 120 ºC. CO (1 MPa); Isolated yield (%); C N (NH ) = melamine, CN H O = Urea.
2
3
3
2 3
2
4
Therefore, we investigated the phase behavior of the catalytic system and the recycling
of the melamine from the aqueous solution. 5 mmol of melamine, 5 mmol of
2
-aminobenzonitrile and 5 ml of water were added into the reactor and heated under vigorous
stirring. When the reaction temperature reached 80 ºC, the catalyst and substrate completely
dissolved in the water and formed a colorless and transparent solution. When the temperature
was continuously increased to 120 ºC, CO was fed at a pressure of up to 4.2 MPa and
2
initially no catalyst-substrate separation was observed. These observations indicated that the
cycloaddition of 1a and CO took place in the homogenous catalytic environment. After the
2
reaction, CO was released slowly, and the product collected by hot filtration at 60 ºC. When
2
the hot aqueous solution was cooled down to 25 ºC, melamine precipitated out. Then the
melamine catalyst could be recrystallized and recovered by further cooling. Thus, an
eco-efficient thermomorphic aqueous catalytic process was developed for the synthesis of
quinazoline-2,4(1H,3H)-diones using CO as substrate, as shown in Scheme 2.
2

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Scheme 2 The smart thermomorphic catalytic aqueous catalytic process for
eco-efficient synthesis of quinazoline-2,4(1H,3H)-diones from CO2.
3
.2 Reaction conditions optimization
Additionally, melamine is thermally stable up to 297 ºC, according to the
Thermogravimetric Analysis (TGA) shown in Fig.2(a). It indicated that the melamine can be
used as a thermally stable catalyst for the synthesis of quinazoline-2,4-(1H,3H)-dione at a
temperature lower than 250 ºC. First, we studied the effect of temperature in a range of 60 –
1
40 ºC on the synthesis of quinazoline-2,4(1H,3H)-dione(1b) using 2-aminobenzonitrile and
CO at 4.2 MPa for 18 hours. The effect of the yield on the temperature is shown in Fig. 2(b).
2
The yield of quinazoline-2,4(1H,3H)-dione increased from 40 – 99% with an increasing
temperature in the low temperature range of 0 – 120 ºC. However, as the reaction temperature
was raised up to 140 ºC, the yield decreased slightly probably because of the reduced CO2
2
8
solubility in water. Therefore, the reaction temperature was fixed at 120 °C for the following
optimization.
Fig. 2 (a) Thermogravimetric analysis of melamine; (b) The effect of temperature on the yield

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of quinazoline-2,4(1H,3H)-dione. Reaction conditions: 2-aminobenzonitrile (5 mmol),
melamine catalyst (10 mol%), water solvent (5 mL), CO (4.2 MPa), 18 h.
2
The effect of reaction time was studied as reference to the yield of
quinazoline-2,4(1H,3H)-dione(1b) at 120 °C, 4.2 MPa and presented in Fig. 3(left). As seen
from Fig. 3, the isolated yield of 1b increased initially with an increasing reaction time
reached 92% after 18 h. No enhancement of the yield was observed with further prolonging
the reaction time. Finally, the effect of CO pressure on the yield of 1b at 120 °C with a
2
reaction time of 18 h was studied. The CO pressure had a considerable effect on the yield of
2
1
b, as shown in Fig. 3(right). Initially, the yield of the product increased dramatically with an
increase in the pressure range from 1 – 4.2 MPa. However, higher pressures did not increase
the yield, which was probably closely related to the opposite tendencies to affect the solubility
of CO and 2-aminobenzonitrile in water.
2
Fig. 3 The effect of reaction time (left) and CO pressure(right) on the yield of
2
quinazoline-2,4(1H,3H)-dione. Reaction conditions: 2-aminobenzonitrile (5 mmol), melamine
(
63 mg,10 mol%), water (5 mL), 120 °C, CO pressure ( fixed 4.2 MPa for left figure and 1 to
2
5
MPa for right figure ), time(12 to 22 h for left figure and fixed 18 h for right figure)

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3
.3 Substrates scope
A variety of substituted 2-aminobenzonitriles was investigated as substrates to react with
CO in the aqueous and thermomorphic catalytic melamine solution at 120 °C and 4.2 MPa.
2
The substrates and corresponding yields are summarized in Table 2. 2-aminobenzonitrile (1a)
with CO gives quinazoline-2,4(1H,3H)-dione(1b) with a yield of 92% (Table 2, entry 1) in
2
1
8 hours. All other aminobenzonitriles (2a-6a) produced the corresponding products with
yields in the range of 80 – 94% in 48 hours. Even the 5-fluoroaminozonitril gave
-fluoroquinazoline-2,4(1H,3H)-dione (6b) with a yield of 80%. All the above results
indicated that melamine is a highly efficient catalyst for these reactions. The products hereby
6
reported
are
important
industrial
gave
intermediates.
94%
For
yield
example,
of
2
6
-amino-4,5-dimethoxybenzonitrile
,7-dimethoxyquinazoline-2,4(1H,3H)-dione (Table 2, entry 2), which is a key intermediate
in the synthesis of Prazosin (Minipress), unazosin (Detantol) and Doxazosin (Cardenalin).
Table 2
Synthesis of various quinazoline-2,4(1H,3H)-diones
b
Entry
1
Substrate
Product
Time(h)
18
Yield (%)
O
NH2
CN
C
NH
92
C
1
a
N
O
H
1
b
O
O
O
NH2
CN
O
O
C
NH
2
18
94
C
2
a
N
H
O
2
b

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Canadian Journal of Chemistry
O
NH2
CN
C
NH
3
4
5
6
24
32
48
32
88
90
82
80
Br
C
3
4
5
6
a
a
a
a
Br
N
H
O
3
4
b
b
O
C
NH2
CN
NH
C
Cl
Cl
Cl
Cl
N
H
O
O
C
NH2
CN
NH
C
N
H
O
5
b
O
C
NH2
CN
NH
C
F
F
N
H
O
6
b
Reaction conditions: reactant (5 mmol), melamine (63 mg, 10 mol%), water (5 mL), CO2
pressure (4.2 MPa), 18 h at 120 C. bIsolated yield (%).
o
3
.4 Recyclability
We also studied the reusability of melamine for the synthesis of
quinazoline-2,4(1H,3H)-dione at 120 ºC, 4.2 MPa, and 18 h according to the strategies
presented in Scheme 2. The cycle-dependent yields are shown in Fig. 4. After the reaction, the
quinazoline-2,4(1H,3H)-dione product was collected via hot filtration, the temperature of
which was fixed at 60 ºC. Then, a fresh substrate and CO were added into the hot and
2
catalytic melamine solution and the reaction was repeated. After four catalytic cycles, the
colour of the catalytic melamine solution turned from milky white to light yellow (Fig.5
(
left)) and its catalytic activity decreased considerably, probably because of the accumulation
of side products. Therefore, after the fourth reaction, the catalytic solution was cooled below
5 ºC to recrystallize the melamine. The recycled melamine was dissolved in fresh water, and
2

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Canadian Journal of Chemistry
reused for the next catalytic runs. 13C NMR spectra show that the structure of the eight
recycled melamine was not changed (Fig.5(right)). The easy product separation and catalyst
recycling by tuning the system temperature are helpful to save energy and minimize process
waste, which are important to practical industrial production.
Fig. 4 Recyclability of melamine for the synthesis of quinazoline-2,4(1H,3H)-dione.
Reaction conditions: 2-aminobenzonitrile (5 mmol), melamine catalyst (63 mg, 10 mol%)),
CO pressure (4.2 MPa), temperature 120 °C, 18 h.
2
1
3
Fig. 5 The C NMR spectrum of the fresh and the recrystallized melamine.
3
.5 A possible cycloaddition pathway.

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According to literature, 2-aminobenzonitrile can be initially activated via the two
different paths as shown in Scheme 3, which is closely related with the basicity of the reaction
system.29-30 With a strong base as catalyst, such as TMG, Cs CO , etc., 1a was firstly attacked
2
3
via the amino carbonylation by CO that generated a carbamate salt intermediate, as shown in
2
equation (1). Otherwise, a carbonate or carbonic acid intermediate formed from CO first
2
attacked the nitrile group of 1a to initialize the reaction as equation (2). The aqueous solution
of melamine/2-aminobenzonitrile is nearly neutral under the reaction conditions. Owing to its
weak basicity, the amino group of 2-aminobenzonitril (pK =0.77) is not easily attacked by
a
CO directly to form the corresponding bicarbonate. Therefore when the CO was introduced
2
2
into the reaction system, the main catalytic specie formed is melamine bicarbonate as the pKa
of melamine is 8. As shown in Scheme 4, the calculated Gibbs free energies and enthalpies
using the Gaussian 09 program also proved our deduction. The large and negative value of the
Gibbs free energy (-23.18 kJ/mol) indicated the ready formation of melamine bicarbonate
with water and CO . Based on the above discussions and previous reports, a possible
2
mechanism for the reaction of 2-aminobenzonitrile and CO in aqueous melamine solutions is
2
hereby proposed (Scheme 5). First, CO reacts with melamine in water to give an intermediate,
2
-
-
melamine bicarbonate-c. Then the hydroxyl OH of HCO migrates to the N atom of the
3
nitrile group of 1a, accompanied by the nucleophilic attack of the carbonyl O atom of HCO3‾
on the C atom of the nitrile group, forming structure-d. Following a series of rearrangement
steps, the structural isomer-f is formed. Finally, with the insertion of CO molecule and the
2

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-
removal of HCO anion, the target product-1b is formed. At the same time, the melamine
3
bicarbonate regenerates and participates in the next catalytic cycle.
Scheme 3
The two different activation paths of 2-aminobenzonitrile.
Scheme 4
The calculated Gibbs free energies and enthalpies of forming the
corresponding bicarbonate.
4
. Conclusion
In summary, an thermomorphic catalytic aqueous process was developed to synthesize
quinazoline-2,4(1H,3H)-dione and its derivatives by cycloaddition of 2-aminobenzonitriles
and CO . Herein, melamine was used as thermomorphic catalyst to produce
2
quinazoline-2,4(1H,3H)-dione efficiently and selectively at 120 ºC, 4.2 MPa, which allowed

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Canadian Journal of Chemistry
the product collection at 60 ºC and catalyst recycling at 25 ºC. We believe this approach
provides an elegant way to produce quinazoline-2,4(1H,3H)-diones from CO2 and
2
-aminobenzonitriles with high step economy and low waste emission.
Scheme 5
A possible mechanisms for the cycloaddition of CO and
2
2
-aminobenzonitrile.
Acknowledgements
This work was financially supported by the National Natural Science Foundation of
China (No. 51374193 and No. 21676278), and the Instrument Developing Project of the
Chinese Academy of Sciences (Grant No. YZ201624). Ling-Ling Mu and Guo-Ying Zhao
contributed equally to this work.

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Canadian Journal of Chemistry
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