A practical synthesis of quinazolinones via intermolecular cyclization between 2-halobenzamides and benzylamines catalyzed by copper(I) immobilized on MCM-41

Article abstract of DOI:10.1016/j.jorganchem.2019.07.003

The heterogeneous tandem N-arylation/oxidative C–H amidation of 2-halobenzamides and benzylamines was achieved in DMSO at 110 or 120 °C by using an MCM-41-immobilized L-proline copper(I) complex [MCM-41-L-Proline-CuBr] as the catalyst and air as the oxidant, yielding a variety of quinazolinone derivatives in good yields. The new MCM-41-L-Proline-CuBr catalyst can easily be prepared from commercially readily available and inexpensive reagents and recovered by filtration of the reaction mixture, and reused up to seven times with almost consistent activity.

Full text of DOI:10.1016/j.jorganchem.2019.07.003

Accepted Manuscript
A practical synthesis of quinazolinones via intermolecular cyclization between 2-
halobenzamides and benzylamines catalyzed by copper(I) immobilized on MCM-41
Nan Yan, Chongren You, Mingzhong Cai
PII:
S0022-328X(19)30286-4
DOI:
https://doi.org/10.1016/j.jorganchem.2019.07.003
JOM 20852
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 13 February 2019
Revised Date: 30 June 2019
Accepted Date: 3 July 2019
Please cite this article as: N. Yan, C. You, M. Cai, A practical synthesis of quinazolinones via
intermolecular cyclization between 2-halobenzamides and benzylamines catalyzed by copper(I)
immobilized on MCM-41, Journal of Organometallic Chemistry (2019), doi: https://doi.org/10.1016/
j.jorganchem.2019.07.003.
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ACCEPTED MANUSCRIPT
A practical synthesis of quinazolinones via intermolecular
cyclization between 2-halobenzamides and benzylamines
catalyzed by copper(I) immobilized on MCM-41
Nan Yan, Chongren You, Mingzhong Cai*
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and
College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang
3
30022, China
ABSTRACT
The heterogeneous tandem N-arylation/oxidative C–H amidation of 2-halobenz-
amides and benzylamines was achieved in DMSO at 110 or 120 ºC by using an
MCM-41-immobilized L-proline copper(I) complex [MCM-41-L-Proline-CuBr] as the
catalyst and air as the oxidant, yielding a variety of quinazolinone derivatives in good
yields. The new MCM-41-L-Proline-CuBr catalyst can easily be prepared from
commercially readily available and inexpensive reagents and recovered by filtration
of the reaction mixture, and reused up to seven times with almost consistent activity.
Keywords: Copper; Quinazolinone; Tandem reaction; Annulation; Heterogeneous
catalysis
1
. Introduction
Quinazolinones are an important class of annulated six-membered N-heterocyclic
compounds and widely occur in many natural products and pharmaceuticals [1,2].
They exhibit a broad range of useful pharmacological and biological activities,
including antibacterial [3], antifungal [4], antimalarial [5], anticancer [6,7], antihyper-
tensive [8], antitubercular [9], anticonvulsant [10], and other activities [11-13]. In
view of their remarkable importance, a number of methods have been developed for
*
Corresponding author.
1
E-mail address: mzcai@jxnu.edu.cn (M. Cai).

ACCEPTED MANUSCRIPT
construction of the quinazolinone skeleton, especially 2-substituted quinazolinones
[
14]. The traditional methods for the synthesis of quinazolinones involve coupling of
ortho-amino or ortho-nitro benzoic acid derivatives with aldehydes [15], alcohols
16,17], and other coupling reagents [18]. However, benzoic acid derivatives bearing
[
ortho-amino or ortho-nitro groups are not readily available or are difficult to prepare.
Recently, copper-catalyzed Ullmann N-arylation reactions have been developed into a
powerful tool for the construction of N-heterocycles [19-29]. Copper-catalyzed
reactions of 2-halobenzoic acid or its derivatives with various ammonia sources such
as benzylamines [30], amidines [31,32], amino acids [33], amides [34], and TMSN3
[
35] have provided an attractive route for the synthesis of quinazolinones owing to
their high efficiency and low price of the catalysts. Besides, other alternative methods
have also been reported using palladium [36-38] and iron [39] catalysts. However,
owing to the homogeneous nature of the reaction, recyclability of the catalyst is rarely
studied since the separation of catalyst and product is often difficult.
For the copper-catalyzed construction of N-heterocycles, the majority of these
reported methods employ expensive/air-sensitive low-valent copper salts with higher
loadings (typically 10 mol%) as the catalysts to achieve high yields. In addition,
homogeneous catalysis might result in unacceptable copper contamination of the
desired product due to the presence of coordination of copper with N-heterocycle
molecules, thus restricting application of these catalytic systems in the synthesis of
drug molecules, which must be free of any residual metal. Immobilization of the
existing homogeneous copper catalysts on various supports could be an attractive
2

ACCEPTED MANUSCRIPT
solution to these problems of particular environmental and economical concerns in
large-scale syntheses and in industry [40-44]. Heterogeneous catalytic systems have
several attractive advantages such as efficient site isolation and good dispersion of
their active sites on solid supports, easy separation of product and catalyst, and
recyclability of catalyst over homogeneous catalytic systems, thereby minimizing
copper contamination of the desired product and waste generated from reaction
workup. In recent years, supported copper catalysts have been successfully applied in
carbon-heteroatom bond formation reactions [45-51]. However, to the best of our
knowledge, no examples of hetereogeneous copper complexes-catalyzed synthesis of
quinazolinones have been described until now.
Mesoporous silica materials such as MCM-41 have recently emerged as powerful
supports for immobilization of homogeneous catalysts as they are advantageous over
other solid supports in terms of ultrahigh surface areas, large and defined pore sizes,
big pore volumes, and high thermal stability [52-54]. So far, Pd [55-58], Rh [59], Mo
[
60], Au [61-63] and Cu [50,51] complexes have been anchored on MCM-41 and the
resulting heterogeneous metal complexes have been successfully applied in various
organic reactions as highly efficient and recyclable catalysts. In continuation of our
interest to develop green and sustainable catalytic systems for organic transforma-
tion, herein we report the synthesis of an MCM-41-immobilized L-proline copper(I)
complex [MCM-41-L-Proline-CuBr] and its application to copper-catalyzed tandem
N-arylation/oxidative C–H amidation between 2-halobenzamides and benzylamines
for the construction of quinazolinones (Scheme 1).
3

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2
. Results and discussion
2
.1. Preparation and characterization of the MCM-41-L-Proline-CuBr complex
The MCM-41-immobilized L-proline copper(I) complex [MCM-41-L-Proline-CuBr]
was prepared from commercially available and inexpensive reagents according to the
procedure as illustrated in Scheme 2. First, the chloromethyl-functionalized MCM-41
[
MCM-41-CH Cl] was obtained by condensation between MCM-41 and 4-(chloro-
2
methyl)phenyltrichlorosilane in toluene, followed by the treatment with anhydrous
ethanol and then the silylation with Me SiCl. Subsequently, MCM-41-CH Cl was
3
2
reacted with N-Boc-trans-4-hydroxy-L-proline in THF with NaH as base, followed by
deprotection with TFA in CH Cl to provide the -proline-functionalized MCM-41
-Proline]. Finally, the reaction of MCM-41- -Proline with CuBr in
acetone at room temperature afforded the MCM-41-immobilized -proline copper(I)
complex [MCM-41- -Proline-CuBr] as pale blue powder. The copper content of this
L
2
2
[
MCM-41-
L
L
L
L
complex was determined to be 0.74 mmol/g by ICP-AES analysis.
The small angle X-ray diffraction (XRD) patterns of the parent MCM-41,
MCM-41-
diffraction pattern of the parent MCM-41 shows an intense diffraction peak (100) at
.34 º and two additional high order peaks (110 and 200) with low intensities at 3.91
and 4.48 º, respectively, which can be attributed to hexagonally ordered mesoporous
structure of MCM-41 [52]. The diffraction pattern of MCM-41- -Proline-CuBr was
L-Proline-CuBr and the used catalyst are illustrated in Fig. 1. The
2
L
similar to that of parent MCM-41, indicating that the MCM-41-L-Proline-CuBr
4

ACCEPTED MANUSCRIPT
complex contains ordered hexagonal arrays of one-dimensional channel structure.
However, the (100) diffraction peak of MCM-41-L-Proline-CuBr with decreased
intensity was observed after functionalization, and the (110) and (200) diffraction
peaks became weak and diffuse, which further confirming that anchoring copper
complex occurs mainly inside mesopore channels. These results indicate that the
mesoporous structure of MCM-41 remains unchanged in the whole preparation
process of the catalyst and the copper complex is well dispersed on the inner channel
walls. The diffraction pattern of the used catalyst was similar to that of MCM-41-
L
-Proline-CuBr, which indicating that the MCM-41 structure was not damaged during
the cyclization reaction, but the intensity of the (100) diffraction peak reduced further
owing to the existence of a trace amount of products in inner channel.
FT-IR spectra of MCM-41, MCM-41-
recovered MCM-41- -Proline-CuBr are shown in Fig. 2. The FT-IR spectrum (Fig. 2a)
of MCM-41 shows the Si–O stretching absorption at 1081 and 802 cm . In the FT-IR
L-Proline, MCM-41-L-Proline-CuBr and the
L
-1
-1
spectrum (Fig. 2b) of MCM-41-
L
-Proline absorptions at 3453 cm (N–H), 1631
-1
(
CO H) and 1404 cm (C–N) were observed indicating the presence of silylated
2
L-Proline groups. After the complexion of CuBr with MCM-41-
L
-Proline, the N–H
-1
stretching frequency is shifted to a higher frequency 3469 cm , while the absorption
-1
bands of CO H and C–N are red shifted and appear at 1626 and 1394 cm ,
2
respectively, demonstrating that –NH and –OH coordinate with the metal Cu (Fig. 2c).
Finally, the FT-IR spectrum (Fig. 2d) of the eighth reused catalyst indicated that the
structure and components of the catalyst remain almost unaltered during the reaction.
5

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N adsorption-desorption isotherms for MCM-41 and MCM-41-
L
-Proline-CuBr are
2
presented in Fig. 3. The isotherms have remarkable changes before and after grafting
the copper complex as expected because the silylated bidentate -Proline-copper(I)
L
complex entered the channels, but both samples gave similar adsorption-desorption
isotherms of type IV (definition by IUPAC), indicating that the mesoporous structure
of MCM-41 was maintained. The pore size distributions for MCM-41 and MCM-41-
L-Proline-CuBr are shown in Fig. 4. The significant drops in pore volume and size
were observed for MCM-41-
-Proline-copper(I) complex into the channels, but the pore still displayed a narrow
distribution. After anchoring the -Proline-copper(I) complex onto MCM-41, the BET
surface area and pore diameter decreased from 921 m /g and 2.7 nm to 593 m /g and
.4 nm, respectively. The energy dispersive spectroscopy (EDS) analysis performed
with fresh MCM-41- -Proline-CuBr complex showed the presence of Si, O, C, N, Br,
L-Proline-CuBr due to the introduction of the silylated
L
L
2
2
2
L
and Cu elements (Fig. 5), also confirming the successful grafting of the
CuBr complex onto MCM-41.
L-Proline-
TGA curves of MCM-41, MCM-41-L-Proline-CuBr and the recovered MCM-41-
L
-Proline-CuBr show the mass loss of the organic materials as they decompose upon
heating (Fig. 6). TGA curve (Fig. 6a) of MCM-41 showed only one mass loss step
between 120 and 280 ºC due to the loss of physically adsorbed water, indicating its
excellent thermal stability. For MCM-41-L-Proline-CuBr, two weight loss steps were
observed (Fig. 6b). The first weight loss step occurs in the temperature range of
1
20-290 ºC, which is related to the loss of physically and chemically adsorbed water
6

ACCEPTED MANUSCRIPT
and organic solvents. The second one occurs in the temperature range of 290-800 ºC
corresponding to the thermal decomposition of organic moieties in the MCM-41-L-
Proline-CuBr catalyst. TGA analysis indicated that this heterogeneous copper catalyst
was stable up to 290 ºC. TGA curve (Fig. 6c) of the eighth reused catalyst displayed
that the catalyst still exhibited high thermal stability even after eight consecutive
cycles.
2
.2. Heterogeneous copper(I)-catalyzed tandem N-arylation/oxidative C–H amidation
of 2-halobenzamides and benzylamines.
The MCM-41-immobilized L-proline copper(I) complex [MCM-41-L-Proline-CuBr]
was then used as catalyst for tandem N-arylation/oxidative C–H amidation of 2-halo-
benzamides and benzylamines. In our initial screening experiments, 2-iodobenzamide
1
a and benzylamine 2a were selected as the model substrates to optimize reaction
conditions, and the results are summarized in Table 1. First, the effect of base on the
model reaction was examined with DMSO as the solvent at 110 ºC (entries 1-4).
When K CO and Na CO were used as bases, the target product 3a was isolated in
2
3
2
3
8
0% and 73% yields, respectively, while Cs CO and K PO afforded lower yields. So
2 3 3 4
the use of K CO as base was the most efficient (entry 2). Replacement of DMSO
2
3
with DMF or ethylene glycol resulted in a dramatic drop in the yield (entries 5 and 6),
whilst dioxane and toluene were ineffective (entries 7 and 8). The effect of reaction
temperatures was also investigated. For the reaction temperatures tested [90, 100, 110,
1
20 and 130 ºC], 110 ºC was the best choice and other reaction temperatures were
substantially less effective (entries 9-12). When the reaction was performed under an
7

ACCEPTED MANUSCRIPT
argon atmosphere, the desired 3a was obtained in only 13% yield along with
formation of N-arylation product, 2-(benzylamino)benzamide in 71% yield (entry 13).
Finally, the amount of the MCM-41-L-Proline-CuBr catalyst was screened, the use of
5
mol% of MCM-41- -Proline-CuBr resulted in a decreased yield and required a
L
longer reaction time (entry 14), increasing the amount of the copper catalyst could
shorten the reaction time, but did not improve the yield significantly (entry 15). When
a homogeneous CuBr (10 mol%) was used as catalyst, the desired product 3a was
isolated in 75% yield (entry 16), which indicating that MCM-41-
exhibited a slightly higher catalytic activity than CuBr. Therefore, the optimized
conditions for this transformation are the use of MCM-41- -Proline-CuBr (10 mol%)
as catalyst in DMSO with K CO as base at 110 °C for 8 h under air (entry 2).
L-Proline-CuBr
L
2
3
With the optimized reaction conditions established, the scope of this heterogeneous
copper-catalyzed tandem reaction between 2-halobenzamides and benzylamines was
examined, and the results are summarized in Table 2. As shown in Table 2. most of
the substrates tested afforded the corresponding quinazolinones in good yields at
110-120 ºC. For instance, the reaction of 2-iodobenzamide 1a with various substituted
benzylamines 2b-2d bearing either electron-donating or electron-withdrawing groups
proceeded smoothly to provide the desired products 3b-3d in 65-87% yields (entries
2
-4). Heteroarylmethanamines such as 2-furylmethanamine 2e, 2-thienylmethanamine
2
f, and 3-pyridinylmethanamine 2g also reacted well in this transformation, thus
furnishing the corresponding products 3e-3g in 67-83% yields (entries 5-7). Bulky
1
-naphthylmethanamine 2h showed a slightly lower reactivity than aryl or hetero-
8

ACCEPTED MANUSCRIPT
arylmethanamines and the reaction with 1a required a higher temperature (120 ºC)
and a longer reaction time (entry 8). 2-Bromobenzamide 1b displayed a slightly lower
reactivity than 1a and the reactions with various aryl or heteroarylmethanamines gave
the corresponding products in slightly lower yields of 70-73% on a longer reaction
time (entries 9-12). Substituted 2-bromobenzamides 1c-1g were also compatible with
the standard reaction conditions, but displayed a slightly lower reactivity than 1b and
a higher temperature (120 ºC) was required (entries 13-27). In general, no obvious
difference of reactivity was observed for the examined substituted 2-bromobenz-
amides with different electronic properties. For example, electron-rich 4-methyl-2-
bromobenzamide 1c and 5-methoxy-2-bromobenzamide 1d could undergo annulation
with various aryl or heteroarylmethanamines to give the corresponding quinazolinone
derivatives 3i-3r in 62-87% yields (entries 13-22). Similarly, the reactions also
worked well with electron-poor 5-fluoro-2-bromobenzamide 1e, 5-chloro-2-bromo-
benzamide 1f, and 4-nitro-2-bromobenzamide 1g, thus providing desired products
3
s-3w in good yields (entries 23-27). However, 2-chlorobenzamides showed low
reactivity, and only 2-chlorobenzamide bearing a strong electron-withdrawing group
could undergo this tandem reaction (entry 28). This heterogeneous copper-catalyzed
tandem synthesis of quinazolinones could tolerate a wide range of functional groups
including methyl, methoxy, fluoro, chloro, and nitro in the substituted 2-halobenz-
amides, methyl, methoxy, fluoro, chloro, a naphthalene ring, and heterocycles
containing nitrogen, oxygen, or sulfur in the arylmethanamines.
2
.3. Leaching test for MCM-41-
L
-Proline-CuBr
9

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To confirm that the observed reaction was due to the heterogeneous MCM-41
L-Proline-CuBr catalyst and not to the leached copper species in solution, we
-
performed the hot filtration test [64]. We focused on the tandem reaction between
-iodobenzamide 1a and benzylamine 2a. We removed the catalyst from the reaction
2
mixture by filtration at 110 ºC after 3 h of reaction time and the catalyst-free filtrate
was allowed to react further with the addition of K CO (2 equiv) under the identical
2
3
conditions for 8 h. It was found that no increase in conversion of 2-iodobenzamide 1a
was observed, verifying that leached copper species from MCM-41- -Proline-CuBr
if any) are not responsible for the observed reaction. In addition, no copper could be
detected in the filtrate by ICP-AES analysis, which revealing negligible copper
leaching. These results indicated that MCM-41- -Proline-CuBr was stable during the
tandem cyclization reaction and actually functioning in a heterogeneous manner.
L
(
L
2
.4. Possible mechanism for the heterogeneous copper(I)-catalyzed domino synthesis
of quinazolinones.
A possible mechanism for the heterogeneous copper(I)-catalyzed domino synthesis
of quinazolinones is shown in Scheme 3. First, heterogeneous copper(I)-catalyzed
Ullmann-type coupling of substituted 2-halobenzamide with arylmethanamine occurs
to form an N-arylation product A. Then heterogeneous copper(I)-catalyzed aerobic
oxidation of intermediate A gives intermediate B containing a C=N bond. Subsequent
intramolecular nucleophilic addition of the amide to the C=N bond in intermediate B
generates intermediate C. Finally, intermediate C undergoes further aerobic oxidation
under the catalysis of MCM-41-L-Proline-CuBr to give the target product 3.
1
0

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2
.5. Recycling of the catalyst
The easy recyclability of the catalyst is highly desirable for the practical application
of a heterogeneous metal catalyst system. In order to evaluate the stability and
recyclability of MCM-41- -Proline-CuBr, the tandem oxidative cyclization between
-methyl-2-bromobenzamide 1c and 4-methoxybenzylamine 2b as model reaction
was investigated under the optimized conditions, and the results are illustrated in Fig.
. After completion of the first reaction cycle, the reaction mixture was diluted with
ethyl acetate and filtered. The washing of the resulting solid with distilled water and
ethanol allowed the easy recovery of MCM-41- -Proline-CuBr. As shown in Fig. 7,
L
4
7
L
the recovered copper catalyst could be reused at least seven times with a slight
decrease in activity. Besides, the recovered catalyst after the eighth run was subjected
-1
to ICP-AES analysis and the copper content was found to be 0.73 mmol g , which
indicating almost consistent Cu content with the fresh one. The excellent reusability
of the MCM-41-
strong interaction between bidentate
on the MCM-41 and to the mesoporous structure of the support.
L
-Proline-CuBr catalyst may be mainly attributed to the relatively
L
-Proline ligand and the copper centre anchored
3
. Conclusions
In conclusion, we have developed an efficient heterogeneous copper(I)-catalyzed
tandem N-arylation/oxidative C–H amidation of 2-halobenzamides and benzylamines
for the construction of quinazolinones, which are found in a number of drug-relevant
molecules and biologically active agents. The reactions generated a wide variety of
11

ACCEPTED MANUSCRIPT
quinazolinone derivatives in good yields and were applicable to a wide range of
2
-halobenzamides and various benzylamines. This new supported copper catalyst can
easily be prepared from readily available and inexpensive materials and recovered by
a simple filtration, and recycled up to eight times with almost consistent activity.
Therefore, the present method is an attractive alternative to construct quinazolinone
derivatives.
4
. Experimental
4
.1. General remarks
All reagents were obtained from commercial sources and used as received without
further purification. All solvents were dried and distilled prior to use. The products
were purified by flash column chromatography on silica gel. A mixture of light
1
13
petroleum ether and ethyl acetate was generally employed as eluent. H NMR and C
NMR spectra were recorded on a Bruker Avance 400 NMR spectrometer (400 MHz
or 100 MHz, respectively) in DMSO-d as solvent with TMS as internal reference.
6
Melting points were determined on a Beijing Tech Instrument Co., LTD X-6 melting
point apparatus and are uncorrected. X-ray powder diffraction patterns were recorded
on Damx-rA (Riguka). Copper content was determined on a Jarrell-Ash 1100 ICP. The
BET surface areas and pore analysis were performed with an ASAP2010 analyzer by
nitrogen adsorption/desorption at 77.4 K. Samples were degassed at 413 K for 12 h
before measurements. Energy dispersive X-ray spectroscopy (EDS) was taken using a
microscope. HRMS spectra were obtained on an AGILENT 6520 Accurate-Mass
1
2

ACCEPTED MANUSCRIPT
QTOF LC/MS spectrometer with the electrospray mode (ES). Mesoporous material
MCM-41 was prepared according to literature method [52].
4
4
.2. Synthesis of the supported copper catalyst
.2.1. Preparation of MCM-41- -Proline
A mixture of MCM-41 (5.0 g) and 4-(chloromethyl)phenyltrichlorosilane (4.8 g) in
L
dry toluene (140 mL) was stirred at 100 °C for 24 h under argon. The reaction product
was filtered and washed by CHCl (30 mL), and dried in vacuum at 130 °C for 2 h.
3
The dried white solid was then reacted with dry ethanol (60 mL) at 80 °C for 24 h
under argon. The resulting product was filtered, washed with Et O (3 × 20 mL), and
2
stirred with Me SiCl (5.2 g) in dry toluene (120 mL) at room temperature for 24 h.
3
The solid product was filtered, washed with acetone (3 × 20 mL), and dried in
vacuum at 100 °C for 6 h to afford 7.143 g of MCM-41-CH Cl with chlorine content
2
of 1.71 mmol/g.
A mixture of N-Boc-trans-4-hydroxy-
1.0 mmol) in dry THF (110 mL) was stirred at 25 °C for 1.5 h under argon. Then
MCM-41-CH Cl (2.0 g) was added and the resulting mixture was stirred at 70 ºC for
L-proline (1.18 g, 5.1 mmol) and NaH (0.26 g,
1
2
2
4 h. After being cooled to room temperature, the product was filtered, washed with
distilled water (2 × 25 mL), ethanol (2 × 25 mL), and dried in vacuum at 100 °C for 3
h. The solid product (1.8 g) was treated with TFA (9 mL) in CH Cl (12 mL) under
2
2
reflux for 4 h, then filtered, and washed with Et N (6 mL), CH Cl (2×10 mL) and
3
2
2
dried in vacuum at 80 °C for 5 h to afford 1.56 g of MCM-41-L-Proline with nitrogen
content of 1.10 mmol/g.
1
3

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4
.2.2. Preparation of MCM-41-L-Proline-CuBr
A mixture of MCM-41- -Proline (1.2 g) and CuBr (0.143 g, 1.0 mmol) in 30 mL of
L
dry acetone was stirred at 25 °C for 12 h under argon. The reaction product was
filtered, washed with acetone (2 × 25 mL) and dried at 80 °C in vacuum for 5 h to
afford 1.285 g of the MCM-41-L-Proline-CuBr catalyst as a light blue powder. The
copper content was determined to be 0.74 mmol/g by ICP-AES analysis.
4
.3. General procedure for the heterogeneous copper(I)-catalyzed synthesis of
quinazolinone derivatives.
To a 10 mL reaction tube were added MCM-41-L-Proline-CuBr (135 mg, 0.1
mmol), 2-halobenzamide 1 (1.0 mmol), benzylamine derivative 2 (2.0 mmol), K CO
2
3
(
3.0 mmol), and DMSO (3 mL). The reaction mixture was stirred at 110 or 120 °C
under air for 6-12 h. After being cooled to room temperature, the reaction mixture was
diluted with 20 mL of EtOAc, and filtered. The MCM-41- -Proline-CuBr complex
L
was washed with distilled water (2 × 5 mL) and ethanol (2 × 5 mL), and reused in the
next run. The filtrate was washed with water (2 × 10 mL) and dried over MgSO4.
After being concentrated in vacuo, the residue was purified by flash column
chromatography on silica gel (petroleum ether/EtOAc = 3:1 to 2:1) to afford the target
product 3.
1
4
.3.1. 2-Phenylquinazolin-4(3H)-one (3a) [28]. White solid. Mp 235–236 ºC. H
NMR (400 MHz, DMSO-d ): δ 12.58 (s, 1H), 8.24-8.18 (m, 3H), 7.86 (t, J = 8.4 Hz,
6
13
1
H), 7.77 (d, J = 8.0 Hz, 1H), 7.65-7.51 (m, 4H). C NMR (100 MHz, DMSO-d ): δ
6
1
4

ACCEPTED MANUSCRIPT
1
62.7, 152.8, 149.2, 135.0, 133.2, 131.8, 129.0, 128.2, 128.0, 127.0, 126.3, 121.5.
4
.3.2. 2-(4-Methoxyphenyl)quinazolin-4(3H)-one (3b) [65]. White solid. Mp 246–247
1
ºC; H NMR (400 MHz, DMSO-d ): δ 12.39 (s, 1H ), 8.19 (d, J = 9.2 Hz, 2H), 8.13 (d,
6
J = 8.0 Hz, 1H), 7.80 (t, J = 8.4 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.48 (t, J = 8.0 Hz,
1
3
1
1
4
H), 7.08 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H). C NMR (100 MHz, DMSO-d ): δ 167.5,
6
67.1, 157.1, 154.2, 139.7, 134.7, 132.5, 131.3, 131.0, 130.0, 125.9, 119.2, 60.7.
1
.3.3. 2-(p-Tolyl)quinazolin-4(3H)-one (3c) [30]. White solid. Mp 261–263 ºC; H
NMR (400 MHz, DMSO-d ): δ 12.46 (s, 1H), 8.17 (d, J = 7.2 Hz, 1H), 8.12 (d, J =
6
8
7
1
.0 Hz, 2H), 7.84 (t, J = 8.2 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H),
1
3
.36 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H). C NMR (100 MHz, DMSO-d ): δ 162.7,
6
52.7, 149.3, 141.9, 135.0, 130.4, 129.6, 128.1, 127.9, 126.8, 126.3, 121.4, 21.4.
4
.3.4. 2-(4-Fluorophenyl)quinazolin-4(3H)-one (3d) [28]. White solid. Mp >300 ºC.
1
H NMR (400 MHz, DMSO-d ): δ 12.55 (br, 1H), 8.24 (dd, J = 8.8, 5.6 Hz, 2H), 8.15
6
(dd, J = 7.8, 1.0 Hz, 1H), 7.83 (t, J = 8.4 Hz, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.52 (t, J =
1
3
7
2
1
4
.2 Hz, 1H), 7.39 (t, J = 9.0 Hz, 2H). C NMR (100 MHz, DMSO-d ): δ 164.5 (d, J =
6
48.0 Hz), 162.7, 151.9, 135.1, 130.8 (d, J = 9.0 Hz), 129.7 (d, J = 2.9 Hz), 128.2,
27.9, 127.1, 126.3, 121.3, 116.1 (d, J = 21.8 Hz).
1
.3.5. 2-(Furan-2-yl)quinazolin-4(3H)-one (3e) [65]. White solid. Mp 220–221 ºC; H
NMR (400 MHz, DMSO-d ): δ 12.54 (s, 1H ), 8.15 (dd, J = 7.8, 1.0 Hz, 1H), 8.03 (d,
6
J = 0.8 Hz, 1H), 7.83 (t, J = 8.2 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 3.2 Hz,
1
3
1
H), 7.51 (t, J = 8.0 Hz, 1H), 6.77 (dd, J = 3.4, 1.8 Hz, 1H). C NMR (100 MHz,
DMSO-d ): δ 162.0, 149.1, 147.0, 146.6, 144.5, 135.1, 127.7, 126.9, 126.4, 121.6,
6
1
5

ACCEPTED MANUSCRIPT
115.0, 113.0.
4
.3.6. 2-(Thiophen-2-yl)quinazolin-4(3H)-one (3f) [30]. White solid. Mp 275–276 ºC;
1
H NMR (400 MHz, DMSO-d ): δ 12.67 (s, 1H), 8.27 (d, J = 3.6 Hz, 1H), 8.15 (d, J =
6
8
.0 Hz, 1H), 7.89 (d, J = 5.2 Hz, 1H), 7.82 (t, J = 8.4 Hz, 1H), 7.67 (d, J = 8.0 Hz,
1
3
1
H), 7.50 (t, J = 8.0 Hz, 1H), 7.26 (t, J = 4.4 Hz, 1H). C NMR (100 MHz,
DMSO-d ): δ 162.3, 149.1, 148.3, 137.9, 135.1, 132.6, 129.9, 128.9, 127.4, 126.8,
6
1
26.5, 121.4.
4
.3.7. 2-(Pyridin-3-yl)quinazolin-4(3H)-one (3g) [30]. White solid. Mp 275–276 ºC;
1
H NMR (400 MHz, DMSO-d ): δ 12.73 (s, 1H), 9.31 (d, J = 2.0 Hz, 1H), 8.77 (dd, J
6
=
4.6, 1.4 Hz, 1H), 8.53–8.44 (m, 1H), 8.18 (dd, J = 7.8, 1.0 Hz, 1H), 7.89–7.83 (m,
1
3
1
1
1
4
2
1
H), 7.78 (d, J = 8.0 Hz, 1H), 7.62–7.53 (m, 2H). C NMR (100 MHz, DMSO-d ): δ
6
62.6, 152.3, 151.3, 149.2, 148.9, 135.9, 135.2, 129.2, 128.0, 127.4, 126.4, 124.0,
21.6.
.3.8. 2-(Naphthalen-1-yl)quinazolin-4(3H)-one (3h) [30]. Light yellow solid. Mp
1
79–281 ºC; H NMR (400 MHz, DMSO-d ): δ 12.68 (s, 1H), 8.24 (d, J = 7.6 Hz,
6
H), 8.18 (d, J = 6.8 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.87
(t, J = 7.0 Hz, 1H), 7.80 (d, J = 6.8 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.6
1
3
Hz, 1H), 7.65–7.56 (m, 3H). C NMR (100 MHz, DMSO-d ): δ 162.4, 154.2, 149.2,
6
1
1
35.0, 133.6, 132.2, 130.9, 130.8, 128.8, 128.2, 127.9, 127.5, 127.3, 126.8, 126.3,
25.7, 125.5, 121.7.
4
.3.9. 7-Methyl-2-phenylquinazolin-4(3H)-one (3i) [66]. White solid. Mp 239–240 ºC;
1
H NMR (400 MHz, DMSO-d ): δ 12.44 (br, 1H), 8.17 (d, J = 6.4 Hz, 2H), 8.03 (d, J
6
1
6

ACCEPTED MANUSCRIPT
1
3
=
8.0 Hz, 1H), 7.62–7.51 (m, 4H), 7.32 (d, J = 8.0 Hz, 1H), 2.45 (s, 3H). C NMR
(
100 MHz, DMSO-d ): δ 162.6, 152.8, 149.3, 145.5, 133.3, 131.8, 129.0, 128.4, 128.2,
6
1
27.6, 126.2, 119.0, 21.8.
4
.3.10. 2-(4-Methoxyphenyl)-7-methylquinazolin-4(3H)-one (3j) [30]. Yellow solid.
1
Mp 246–248 ºC; H NMR (400 MHz, DMSO-d ): δ 12.28 (s, 1H), 8.16 (d, J = 8.8 Hz,
6
2
H), 7.99 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.06 (d, J = 8.8
13
Hz, 2H), 3.82 (s, 3H), 2.43 (s, 3H). C NMR (100 MHz, DMSO-d ): δ 162.6, 162.3,
6
1
52.3, 149.5, 145.4, 129.8, 128.0, 127.4, 126.1, 125.4, 118.8, 114.4, 55.9, 21.8.
4
.3.11. 2-(Furan-2-yl)-7-methylquinazolin-4(3H)-one (3k) [30]. Light yellow solid.
1
Mp 240–241 ºC; H NMR (400 MHz, DMSO-d ): δ 12.39 (s, 1H), 7.98 (d, J = 6.4 Hz,
6
2
1
1
4
H), 7.60 (d, J = 3.6 Hz, 1H), 7.47 (s, 1H), 7.28 (d, J = 8.0 Hz, 1H), 6.73 (dd, J = 7.6,
1
3
.6 Hz, 1H), 2.43 (s, 3H). C NMR (100 MHz, DMSO-d ): δ 161.9, 149.2, 146.9,
6
46.6, 145.5, 144.5, 128.3, 127.4, 126.2, 119.2, 114.8, 112.9, 21.8.
.3.12. 7-Methyl-2-(thiophen-2-yl)quinazolin-4(3H)-one (3l) [30]. Light yellow solid.
1
Mp 290–291 ºC; H NMR (400 MHz, DMSO-d ): δ 12.54 (br, 1H), 8.22 (d, J = 3.6
6
Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 4.8 Hz, 1H), 7.47 (s, 1H), 7.31 (d, J =
1
3
8
1
2
4
2
8
.0 Hz, 1H), 7.24 (t, J = 4.4 Hz, 1H), 2.46 (s, 3H). C NMR (100 MHz, DMSO-d ): δ
6
62.1, 149.2, 148.3, 145.7, 138.0, 132.5, 129.7, 128.9, 128.2, 127.1, 126.3, 118.9,
1.8.
.3.13. 7-Methyl-2-(pyridin-3-yl)quinazolin-4(3H)-one (3m). White solid. Mp 256–
1
58 ºC; H NMR (400 MHz, DMSO-d ): δ 12.59 (br, 1H), 9.28 (d, J = 2.0 Hz, 1H),
6
.74 (dd, J = 4.8, 1.6 Hz, 1H), 8.49–8.44 (m, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.56 (dd, J
1
7

ACCEPTED MANUSCRIPT
1
3
=
8.2, 5.4 Hz, 1H), 7.53 (s, 1H), 7.33 (dd, J = 8.0, 1.2 Hz, 1H), 2.45 (s, 3H). C NMR
(
100 MHz, DMSO-d ): δ 162.4, 152.2, 151.1, 149.2, 149.1, 145.6, 135.7, 129.2, 128.8,
6
+
+
1
27.6, 126.2, 123.9, 119.2, 21.8. HRMS calcd for C H N O [M+H] : 238.0980,
14 12 3
found 238.0982.
4
.3.14. 6-Methoxy-2-phenylquinazolin-4(3H)-one (3n) [66]. White solid. Mp 248–250
1
ºC; H NMR (400 MHz, DMSO-d ): δ 12.52 (br, 1H), 8.16 (d, J = 9.2 Hz, 2H), 7.70
6
(d, J = 8.8 Hz, 1H), 7.58–7.50 (m, 4H), 7.44 (dd, J = 9.0, 3.0 Hz, 1H), 3.90 (s, 3H).
1
3
C NMR (100 MHz, DMSO-d ): δ 162.5, 158.2, 150.6, 143.7, 133.3, 131.5, 129.7,
6
1
4
2
2
7
29.0, 128.0, 124.6, 122.2, 106.3, 56.1.
.3.15. 6-Methoxy-2-(4-methoxyphenyl)quinazolin-4(3H)-one (3o). White solid. Mp
1
58–259 ºC; H NMR (400 MHz, DMSO-d ): δ 12.38 (br, 1H), 8.16 (d, J = 8.8 Hz,
6
H), 7.66 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 3.2 Hz, 1H), 7.43 (dd, J = 8.8, 3.0 Hz, 1H),
1
3
.08 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.85 (s, 3H). C NMR (100 MHz, DMSO-d ):
6
δ 162.6, 162.1, 157.9, 150.3, 143.7, 129.6, 129.3, 125.3, 124.5, 121.9, 114.4, 106.4,
+
+
5
6.1, 55.9. HRMS calcd for C H N O [M+H] : 283.1083, found 283.1078.
16 15 2 3
4
.3.16. 2-(4-Chlorophenyl)-6-methoxyquinazolin-4(3H)-one (3p). White solid.
1
Mp >300 ºC; H NMR (400 MHz, DMSO-d ): δ 12.56 (br, 1H), 8.17 (d, J = 8.4 Hz,
6
2
H), 7.69 (d, J = 8.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 3.2 Hz, 1H), 7.44
1
3
(
dd, J = 8.8, 2.8 Hz, 1H), 3.89 (s, 3H). C NMR (100 MHz, DMSO-d ): δ 162.4,
6
1
58.4, 149.6, 143.5, 136.4, 132.1, 129.8, 129.7, 129.1, 124.6, 122.3, 106.4, 56.1.
+
2
+
HRMS calcd for C H ClN O [M+H] : 287.0587, found 287.0581.
1
5
12
2
4
.3.17. 6-Methoxy-2-(thiophen-2-yl)quinazolin-4(3H)-one (3q) [30]. Light yellow
1
8

ACCEPTED MANUSCRIPT
1
solid. Mp 261–262 ºC; H NMR (400 MHz, DMSO-d ): δ 12.63 (br, 1H), 8.20 (d, J =
6
3
.6 Hz, 1H), 7.83 (d, J = 4.8 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 2.8 Hz,
1
3
1
H), 7.41 (dd, J = 9.0, 3.0 Hz, 1H), 7.24–7.20 (m, 1H), 3.89 (s, 3H). C NMR (100
MHz, DMSO-d ): δ 162.0, 158.1, 146.3, 143.5, 138.0, 131.9, 129.2, 128.8, 128.7,
6
1
4
3
8
24.5, 122.2, 106.7, 56.1.
.3.18. 6-Methoxy-2-(1-naphthalenyl)quinazolin-4(3H)-one (3r). Yellow solid. Mp >
1
00 ºC; H NMR (400 MHz, DMSO-d ): δ 12.64 (s, 1H), 8.18 (d, J = 7.2 Hz, 1H),
6
.17-8.10 (m, 1H), 8.06-8.03 (m, 1H), 7.79 (dd, J = 7.2, 0.8 Hz, 1H), 7.70 (d, J = 8.8
1
3
Hz, 1H), 7.67–7.56 (m, 4H), 7.47 (dd, J = 8.8, 3.2 Hz, 1H), 3.93 (s, 3H). C NMR
(
100 MHz, DMSO-d ): δ 162.2, 158.4, 151.8, 143.7, 133.6, 132.2, 130.8, 130.7, 129.7,
6
1
28.8, 128.1, 127.5, 126.8, 125.7, 125.5, 124.4, 122.5, 106.4, 56.2. HRMS calcd for
+
+
C H N O [M+H] : 303.1134, found 303.1127.
19
15
2
2
1
4
.3.19. 6-Fluoro-2-phenylquinazolin-4(3H)-one (3s). White solid. Mp 232–233 ºC; H
NMR (400 MHz, DMSO-d ): δ 12.69 (br, 1H), 8.17 (d, J = 6.8 Hz, 2H), 7.86–7.80 (m,
6
1
3
2
H), 7.75 (dd, J = 8.6, 3.0 Hz, 1H), 7.63–7.54 (m, 3H). C NMR (100 MHz,
DMSO-d ): δ 162.1, 160.4 (d, J = 243.9 Hz), 152.4, 146.1, 133.0, 131.9, 130.7 (d, J =
6
4
.0 Hz), 129.1, 128.2, 123.5 (d, J = 23.9 Hz), 122.6 (d, J = 8.3 Hz), 110.9 (d, J = 23.2
+
+
Hz). HRMS calcd for C H FN O [M+H] : 241.0777, found 241.0783.
1
4
10
2
4
.3.20. 6-Chloro-2-phenylquinazolin-4(3H)-one (3t) [28]. White solid. Mp 294–295
1
ºC; H NMR (400 MHz, DMSO-d ): δ 12.68 (br, 1H), 8.16 (d, J = 7.2 Hz, 2H), 8.08
6
(d, J = 2.0 Hz, 1H), 7.87–7.83 (m, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.63–7.53 (m, 3H).
1
3
C NMR (100 MHz, DMSO-d ): δ 161.8, 153.3, 147.9, 135.1, 132.9, 132.1, 131.2,
6
1
9

ACCEPTED MANUSCRIPT
1
4
2
30.2, 129.1, 128.3, 125.3, 122.7.
.3.21. 6-Chloro-2-(thiophen-2-yl)quinazolin-4(3H)-one (3u) [30]. White solid. Mp
1
70–272 ºC; H NMR (400 MHz, DMSO-d ): δ 12.81 (br, 1H), 8.24 (dd, J = 3.8, 1.0
6
Hz, 1H), 8.05 (d, J = 2.4 Hz, 1H), 7.89 (dd, J = 5.0, 1.0 Hz, 1H), 7.81 (dd, J = 8.8, 2.4
1
3
Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.25 (dd, J = 5.0, 3.8 Hz, 1H). C NMR (100 MHz,
DMSO-d ): δ 161.3, 148.7, 147.9, 137.5, 135.1, 132.9, 130.9, 130.2, 129.6, 129.0,
6
1
25.5, 122.5.
4
.3.22. 7-Nitro-2-phenylquinazolin-4(3H)-one (3v) [30]. Yellow solid. Mp >320 ºC;
1
H NMR (400 MHz, DMSO-d ): δ 12.91 (br, 1H), 8.44 (d, J = 2.4 Hz, 1H), 8.37 (d, J
6
13
=
8.4 Hz, 1H), 8.26–8.20 (m, 3H), 7.67–7.55 (m, 3H). C NMR (100 MHz,
DMSO-d ): δ 161.9, 155.1, 151.8, 149.6, 132.6, 132.5, 129.2, 128.6, 128.5, 125.8,
6
1
22.8, 120.5.
4
.3.23. 2-(Furan-2-yl)-7-nitroquinazolin-4(3H)-one (3w). Yellow solid. Mp 285–287
1
ºC; H NMR (400 MHz, DMSO-d ): δ 12.43 (s, 1H), 9.29 (d, J = 1.6 Hz, 1H), 9.24 (d,
6
J = 2.4 Hz, 1H), 8.45 (d, J = 8.8 Hz, 1H), 8.39 (d, J = 2.0 Hz, 1H), 8.33 (dd, J = 8.8,
1
3
2
1
.4 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H). C NMR (100 MHz, DMSO-d ): δ 160.1,
6
51.0, 142.8, 142.2, 134.6, 130.2, 126.0, 123.4, 120.9, 119.5, 117.7, 117.1. HRMS
+
4
+
calcd for C H N O [M+H] : 258.0515, found 258.0518.
1
2
8
3
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21462021) and
Key Laboratory of Functional Small Organic Molecule, Ministry of Education (No.
KLFS-KF-201704) for financial support.
2
0

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ACCEPTED MANUSCRIPT
Scheme 1. Heterogeneous copper-catalyzed synthesis of quinazolinones.
Scheme 2. Preparation of the MCM-41-L-Proline-CuBr complex.
O
O
MCM-41-L-Proline-CuBr
K CO
NH2
2
3
NH2
H N
2
R
+
R
R
R1
Ullmann-type coupling
R1
X
N
1
2
H
(
A)
O
O
MCM-41-L-Proline-CuBr
K CO , air
NH2
NH
2
3
R
addition
aerobic oxidation
R1
N
H
C)
R1
N
B)
(
(
O
MCM-41-L-Proline-CuBr
K CO , air
2
3
NH
R
aerobic oxidation
R1
N
3
Scheme 3. Proposed catalytic cycle.
2
5

ACCEPTED MANUSCRIPT
a
Table 1 Optimization of the reaction conditions.
b
Entry
Base
Solvent
DMSO
DMSO
DMSO
DMSO
DMF
Temp. (ºC)
110
Yield (%)
1
2
3
4
5
6
7
8
9
Cs CO3
47
2
K CO3
2
110
80
Na CO3
110
73
2
K PO4
3
110
54
K CO3
2
110
17
K CO3
2
ethylene glycol
dioxane
toluene
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
110
23
K CO3
2
110
0
K CO3
2
110
0
K CO3
2
100
90
65
10
K CO3
2
48
11
K CO3
2
120
130
110
77
12
13
14
15
16
K CO3
2
73
c
d
e
f
K CO3
2
13
K CO3
2
110
66
K CO3
2
110
81
K CO3
2
110
75
a
Reaction conditions: 1a (1.0 mmol), 2a (2.0 mmol), MCM-41-L-Proline-CuBr (10 mol%), base
b
c
d
(
3.0 mmol), solvent (3 mL) under air for 8 h. Isolated yield. Reaction was conducted under Ar.
e
5
mol% of MCM-41-L-Proline-CuBr was used for 20 h. 20 mol% of MCM-41-L-Proline-CuBr
f
was used for 5 h. CuBr (10 mol%) was used.
2
6

ACCEPTED MANUSCRIPT
a
Table 2 Heterogeneous copper-catalyzed synthesis of quinazolinone derivatives.
O
O
MCM-41-L-Proline-CuBr (10 mol%)
NH2
NH
H N
2
R
+
R
Ar
K CO , DMSO, air
2
3
X
N
Ar
X = I, Br, Cl
2
3
1
Temp.
ºC)
Time
(h)
Yield
(%)
Entry R
X
Ar
Ph
Product
b
(
1
2
3
4
5
6
7
8
9
0
H
I
110
110
110
110
110
110
110
120
110
110
110
110
120
120
120
120
120
120
120
120
120
120
8
3a
3b
3c
3d
3e
3f
80
87
83
65
67
83
81
71
71
73
70
71
77
87
62
80
85
71
70
67
86
75
H
I
4-MeOC H
8
6
4
H
I
4-MeC H
8
6
4
H
I
4-FC H
8
6
4
H
I
2-furyl
8
H
I
2-thienyl
8
H
I
3-pyridinyl
1-naphthyl
Ph
8
3g
3h
3a
3b
3g
3f
H
I
11
10
10
10
10
10
10
10
10
8
H
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
1
H
4-MeOC H
6
4
11
H
3-pyridinyl
2-thienyl
Ph
12
13
14
15
16
17
18
19
20
21
22
H
4-Me
4-Me
4-Me
4-Me
4-Me
5-MeO
5-MeO
5-MeO
5-MeO
5-MeO
3i
4-MeOC H
3j
6
4
2-furyl
2-thienyl
3-pyridinyl
Ph
3k
3l
3m
3n
3o
3p
3q
3r
12
12
12
12
12
4-MeOC H
6
4
4-ClC H
6
4
2-thienyl
1-naphthyl
2
7

ACCEPTED MANUSCRIPT
23
24
25
26
27
28
5-F
Br
Br
Br
Br
Br
Cl
Ph
120
120
120
120
120
130
8
3s
67
73
75
73
65
47
5-Cl
5-Cl
Ph
10
10
6
3t
2-thienyl
Ph
3u
3v
3w
3v
4-O N
2
4-O N
2-furyl
Ph
10
16
2
4-O N
2
a
Reaction conditions: 1 (1.0 mmol), 2 (2.0 mmol), MCM-41-L-Proline-CuBr (10 mol%), K CO
2
3
b
(
3.0 mmol), DMSO (3 mL) under air. Isolated yield.
Fig. 1. XRD patterns of MCM-41, MCM-41-L-Proline-CuBr and the recovered
MCM-41- -Proline-CuBr.
L
Fig. 2. FT-IR spectra of MCM-41 (a), MCM-41-L-Proline (b), MCM-41-L-Proline-
CuBr (c) and the recovered MCM-41- -Proline-CuBr after the eighth cycle (d).
L
2
8

ACCEPTED MANUSCRIPT
Fig. 3. N adsorption/desorption isotherms of MCM-41 and MCM-41-
L
-Proline-
2
CuBr.
Fig. 4. Pore size distributions of MCM-41 and MCM-41-L-Proline-CuBr.
Fig. 5. EDS pattern of MCM-41-L-Proline-CuBr
2
9