An efficient synthesis of N-substituted phthalimides using SiO2-tpy-Nb as heterogeneous and reusable catalyst

Article abstract of DOI:10.1016/j.catcom.2016.09.005

A novel and efficient heterogeneous catalyst SiO₂-tpy-Nb was developed, and its application in the preparation of N-substituted phthalimides from o-phthalic acids or anhydrides with amines provides the desired products in good to excellent yields. The catalyst was stable and recoverable for eight consecutive cycles without a significant loss in its activity. Furthermore, the catalyst is applicable in continuous flow which indicates its potential utilization in industrialization.

Full text of DOI:10.1016/j.catcom.2016.09.005

An efficient synthesis of N-substituted phthalimides using SiO2-tpy-Nb as
heterogeneous and reusable catalyst
Li Wan, Xiaoning Sun, Songjie Shi, Jiawei Zhang, Xin Li, Zhenjiang
Li, Kai Guo
PII:
DOI:
Reference:
S1566-7367(16)30319-3
doi:10.1016/j.catcom.2016.09.005
CATCOM 4774
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
7 July 2016
19 August 2016
6 September 2016
Please cite this article as: Li Wan, Xiaoning Sun, Songjie Shi, Jiawei Zhang, Xin
Li, Zhenjiang Li, Kai Guo, An efficient synthesis of N-substituted phthalimides using
SiO2-tpy-Nb as heterogeneous and reusable catalyst, Catalysis Communications (2016),
doi:10.1016/j.catcom.2016.09.005
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

ACCEPTED MANUSCRIPT
Page 1 of 14
An efficient synthesis of N-substituted phthalimides using
SiO2-tpy-Nb as heterogeneous and reusable catalyst
Li Wan,†,§ Xiaoning Sun,† Songjie Shi,† Jiawei Zhang,† Xin Li,† Zhenjiang Li,† and Kai Guo*,†,‡,§
†College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing
211816, P. R. China
‡State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University,
Nanjing 210009, P. R. China
§Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), 30 Puzhu South
Road, Nanjing 211816, P. R. China
ABSTRACT:
A novel and efficient heterogeneous catalyst SiO2-tpy-Nb was developed, and its application in the
preparation of N-substituted phthalimides from o-phthalic acids or anhydrides with amines
provides the desired products in good to excellent yields. The catalyst was stable and recoverable
for eight consecutive cycles without a significant loss in its activity. Furthermore, the catalyst is
applicable in continuous flow which indicates its potential utilization in industrialization.
Keywords: phthalimide, niobium, terpyridine, heterogeneous, continuous flow
INTRODUCTION
The cyclic imides especially phthalimide and its derivatives are a core motif of numerous
natural products and designed pharmaceutical molecules due to their broad range of applications
as anti-inflammtories, anticonvulsants, analgesics, immunomodulatory, herbicidal and insecticidal
agents [1-4]. Moreover, phthalimide analogues have found extensive utilization as dyes, polymers,
and in different branches of material sciences [5,6]. Owing to the increasing biological and
industrial importance of cyclic imides especially phthalimide and its derivatives, the synthetic
*Corresponding author: Kai Guo
E-mail: guok@njtech.edu.cn

ACCEPTED MANUSCRIPT
Page 2 of 14
methodology of these molecules has emerged as a topic of interest for synthetic chemists. The
most commonly used strategy for the synthesis of phthalimides involves condensation of phthalic
acids or anhydrides and primary amines in refluxing organic solvents [7]. Those high boiling point
solvents such as acetic acid, DMF, and dioxane are mostly used in the preparation of phthalimides
[8]. Synthesis in solvent-free conditions also could be achieved by refluxing a mixture of phthalic
anhydride with the amine [9] or by utilizing DABCO as catalyst at room temperature [10]. In
addition, microwave irradiation as a heating method was also investigated in the presence or
absence of organic solvents [11]. Generally, high yields of phthalimides were given within just a
few minutes. Besides, ionic liquids attract considerable interest in the context of green synthesis
because of their wide acceptability as alternative green reaction media. However, most of the
traditional methods are not entirely satisfactory due to lengthy reaction times, the use of toxic
solvents and auxiliary reagents. And the ionic liquids still suffer from the relatively expensive cost
for practical utilization.
Recently, many novel synthetic routes from nitriles, halides, alkyne, cyclic amines,
isocyanates, and phthalimide using transition-metal catalysis or excess amounts of I(III) oxidant
have been reported [12-14], but most of them are homogeneous catalytic methods which bring the
concern of difficulties in catalyst/products separation, reusability of expensive catalysts and heavy
metal contamination in pharmaceutical applications. In regard to the development of efficient,
economical and greener protocol with additional advantage of catalyst recyclability,
heterogeneous catalyst is emerging as an alternative over previous homogeneous protocols. Very
recently, water-tolerant Nb2O5 was used as Lewis acid catalyst in various organic reactions
[15-17]. Meanwhile, Shimizu and co-workers discovered that Nb2O5 exhibited base-tolerant
catalytic activity for the direct cyclic imide synthesis from dicarboxylic acids with amines and
ammonia under mild conditions [18,19]. Generally, the Nb2O5 catalyst was prepared by
.
calcination from commercial niobic acid Nb2O5 nH2O, which is readily prepared by the hydrolysis
of NbCl5 or Nb(OC2H5)5. High yields of phthalimides from dicarboxylic acid with various amines
were obtained, and the catalyst Nb2O5 exhibited good recyclability. To further expand the
application of metal niobium, water soluble niobium oxalate was chosen as the source of niobium.
Then we dedicated to investigate an efficient and reusable heterogeneous niobium catalyst, and
applied it in continuous flow system to synthesis phthalimides successional.

ACCEPTED MANUSCRIPT
Page 3 of 14
In the past few decades, silica gel is widespread used as support in the field of heterogeneous
catalyst. Because it is very cheap and easily functionalization to anchor the desired ligands to the
surface [20]. Lately, polypyridyl transition-metal complexes have received much attention in the
field of ion sensors [21,22]. And a great number of polypyridyl complexes have been used as
optical sensors for various anions and metal cations by taking advantage of their distinguished
photophysical properties [23,24]. Simultaneously, the terpyridines as tridentate ligands have
gained increasing interest because of their efficient and stable chelating ability to transition metals
[25]. Terpyridine nickel and palladium complexes have been used to catalyze classical
cross-coupling reactions, and satisfactory results were obtained [26-28]. Herein, we wish to
describe an novel alternative method using silica gel supported the complex of terpyridine (tpy)
with niobium oxalate as catalyst to produce phthalimide derivatives from o-phthalic acids or
anhydrides and amines as the reagents.
EXPERIMENTAL SECTION
General procedure for the synthesis of cyclic imides. In a 25 mL sealed tube, the
corresponding dicarboxylic acid or anhydrate (0.3 mmol), amine (0.3 mmol), catalyst SiO2-tpy-Nb
o
(10 mol%) were stirred in 1 mL IPA:H2O = 1:2 at 110 C for 14 h. After the reaction completed,
the mixture was cooled to room temperature and extracted with ethyl acetate (20 mL × 3). The
combined organic layer was dried over anhydrous Na2SO4, filtered and the solvent was evaporated
under vacuum. The residue was purified by flash chromatography using EtOAc/n-hexene as eluent
to afford the products.
Recycling of the silica-immobilized catalyst. In a 25 mL sealed tube, o-phthalic anhydride (0.3
mmol), p-toluidine (0.3 mmol), catalyst SiO2-tpy-Nb (10 mol%) were stirred in 1 mL IPA:H2O =
1:2 at 110 oC for 14 h. After the reaction completed, the mixture was diluted with ethyl acetate (20
mL). The catalyst was filtered and washed with EtOAc (30 mL × 3), H2O (30 mL × 2), EtOH (10
mL). Then the catalyst was dried under vacuum at 60 oC for 6 h for next cycle.
Procedure for the model reaction in continuous flow system. The packed-bed reactor of
catatlyst SiO2-tpy-Nb was assembled according to the procedures in previous literatures [29,30].
1.5 g catalyst was packed in a PFA tube (OD 11.25 mm, ID 7.25 mm), then the tube was put into
an air bath. The inlet of the reactor was connected to a HPLC pump via PFA tubing and the outlet

ACCEPTED MANUSCRIPT
Page 4 of 14
of the reactor was connected with a back-pressure regulator (8 bar). The reactor was heated in an
o
air bath (110 C) and flushed with the solvent (IPA:H2O=1:2). A flask fitted with rubber cap was
charged with o-phthalic anhydride (6.0 mmol), p-toluidine (6.0 mmol) and 60 mL IPA:H2O = 1:2.
The flow rate of starting materials was set to be 20.0 μL/min, the residence time was 30 min. After
reaching steady state (15-20 min as monitored by GC analysis), the resulting mixture was
collected into test tubes. The crude reaction mixture was diluted with EtOAc, and then filtered
through celite before GC analysis.
RESULTS AND DISCUSSION
The detail of preparation of heterogeneous catalyst SiO2-tpy-Nb was illustrated in the
supporting information [31]. The loading of terpyridine was determined to be 1.01 mmol/g by
means of the nitrogen content calculated by elemental analysis. The content of niobium was 0.89
mmol/g based on the analysis of ICP result. Scanning electron micrography (SEM) was recorded
to understand morphology of the surface of SiO2-tpy and SiO2-tpy-Nb. As can be seen from
Figure 1, the particle size of silica supported tpy-Nb (Figure 1B) is similar to the silica support tpy
(Figure 1A). It demonstrates that the particles of SiO2-tpy has a good mechanical stability during
the immobilization step. Meanwhile, the surface morphology of these two samples are different
evidently. It shows that the surface of SiO2-tpy was slick, but roughness on the surface of
SiO2-tpy-Nb was observed which implied the presence of niobium oxalate.
(A)
(B)
(C)
Figure 1. SEM images of (A) SiO2-tpy; (B) SiO2-tpy-Nb; (C) reused SiO2-tpy-Nb after 8th cycle
In order to evaluate the activity of silica supported tpy-Nb in the synthesis of phthalimide,
o-phthalic acid and p-toluidine were chosen as model substrates. In the preliminary experiments,
the reaction was carried out in various solvents with the catalyst SiO2-tpy-Nb (10 mol% of
niobium content) at 100 oC for 14 h. As is shown in Table 1, the polar solvents of various alcohols

ACCEPTED MANUSCRIPT
Page 5 of 14
gave better yields than EtOAc. Similar yields were obtained in CF3CH2OH, isopropanol, n-butyl
alcohol and 2-methyl-2-butanol (Table 1, entries 3 to 7). To develop an economic and
environmentally friendly reaction system, we employed water as the solvent in the reaction.
Slightly increase in the yield was observed in the model reaction (Table 1, entry 10). Therefore,
we utilized the organic/aqueous co-solvent to investigate the optimal reaction conditions. The
combination of three alcohols with water were screened in different volume ratio (Table 1, entries
11 to 19). The highest yield was obtained in the co-solvent of IPA:H2O=1:2 (Table 1, entry 17).
The yield decreased to 72% when the ratio of water increased to 1:4 (Table 1, entry 20). Next, we
o
o
o
test the influence of reaction temperature at 90 C, 110 C, 120 C respectively. Excellent yield
o
was obtained when the reaction was performed at 110 C (Table 1, entry 22). Thus, we selected
o
IPA:H2O=1:2 as the solvent and 10 mol% of catalyst at 110 C as the optimal conditions for the
synthesis of phthalimides. And compared to niobium oxalate, 79% conversion of starting material
was given under the optimal conditions (Table 1, entry 24). It indicated the catalyst SiO2-tpy-Nb
was more efficient in this reaction.
Table 1 Optimization of reaction conditionsa
Entry
Solvent
EtOAc
Temp. (oC)
100
Conversion(%)b
1
2
3
4
5
6
11
19
32
38
36
37
CH3OH
100
EtOH
100
CF3CH2OH
isopropanol (IPA)
n-butyl alcohol
(NBA)
100
100
100
7
2-methyl-2-butanol
(TAA)
100
39
8
tert-butanol (TBA)
isobutanol (IBA)
H2O
100
100
100
100
100
100
100
100
13
34
53
52
41
36
52
61
9
10
11
12
13
14
15
NBA:H2O=1:2
NBA:H2O=1:1
NBA:H2O=2:1
TAA:H2O=1:2
TAA:H2O=1:1

ACCEPTED MANUSCRIPT
Page 6 of 14
16
17
18
19
20
21
22
23
24d
25e
TAA:H2O=2:1
IPA:H2O=1:2
IPA:H2O=1:1
IPA:H2O=2:1
IPA:H2O=1:4
IPA:H2O=1:2
IPA:H2O=1:2
IPA:H2O=1:2
IPA:H2O=1:2
IPA:H2O=1:2
100
100
100
100
100
90
46
83
75
65
72
78
95 (90)c
110
120
110
110
89
79
75
a Reaction conditions: o-phthalic acid (0.3 mmol), p-toluidine (0.3 mmol), SiO2-tpy-Nb (10 mol%),
b
c
d
solvent (1.0 mL), 14 h. Determined by the analysis of GC results. Isolated yield. The catalyst
was niobium oxalate. e The catalyst was Niobic acid (Nb2O5∙nH2O).
To survey the generality of the catalytic protocol, a variety of substituted o-phthalic acids and
amines were tested under the optimized conditions. Good to excellent yields were obtained from
o-phthalic acid with different groups substituted anilines (Table 2, 3a-3d). Although the
substituent 2,6-diisopropyl is bulky, the desired product was still given in 84% yield (Table 2, 3b).
This result implies the steric effect is negligible in our catalytic system. Only moderate yields
were obtained when chlorine substituted at 4 and 5 position of o-phthalic acid (Table 2, 3e and 3f),
except for the reaction with 4-fluoroaniline (Table 2, 3g). Nevertheless, electron-donating group
substituted o-phthalic acid produced the corresponding products in satisfied yields with anilines
substituted by methyl and chlorine (Table 2, 3h and 3i). Meanwhile, electron-rich and
electron-poor benzylamines exhibited highly reactivity with o-phthalic acid to obtain the desired
phthalimides in good yields (Table 2, 3j-3l).
Table 2 Substrate scope of various o-phthalic acids with aminesa,b

ACCEPTED MANUSCRIPT
Page 7 of 14
a Reaction conditions: substituted o-phthalic acid (0.3 mmol), amine (0.3 mmol), SiO2-tpy-Nb (10
mol%), IPA:H2O=1:2 (1.0 mL), 14 h. b Isolated yields are given in parentheses.
Next, commercial available or easily prepared o-phthalic anhydrides were explored with a
broad range of amine under the optimal conditions. As a result, both electron-rich as well as
electron-poor anilines and benzylamines gave good to excellent yields of the corresponding
phthalimides (Table 3, 5a-5k). Halogen substituents (Table 3, 5b, 5f, 5i, 5k) were well tolerated
by the catalytic system, which should prove useful for further functionalizations by cross-coupling
chemistry. Gratifyingly, high yields were obtained from 2-furanmethanamine with o-phthalic
anhydrides (Table 3, 5l-5m). In addition, low activity amines, such as cyclohexylamine,
cyclopentylamine and propylamine, were reacted with 4-methylphthalic anhydride to afford the
desired products in moderate yields. Notably, good yield was obtained from 3-aminopropynethe,
the corresponding product which has significant utilization in the synthesis of potential anticancer
agents [32], hybrid crown macrocycles [33] and novel polymeric materials [34].
Table 3 Substrate scope of various o-phthalic anhydrides with aminesa,b

ACCEPTED MANUSCRIPT
Page 8 of 14
a
Reaction conditions: substituted o-phthalic anhydride (0.3 mmol), amine (0.3 mmol),
SiO2-tpy-Nb (10 mol%), IPA:H2O=1:2 (1.0 mL), 14 h. b Isolated yields are given in parentheses.
For a heterogeneous catalyst, it is important to examine its ease of separation and good
reusability. The recyclability of the prepared catalyst SiO2-tpy-Nb was investigated in the reaction
of o-phthalic anhydride with p-toluidine under the optimal conditions. After carrying out the
reaction, the mixture was diluted with ethyl acetate and filtered. The catalyst was separated by
simple filtration and washed with ethyl acetate several times. Then the catalyst was dried under
vacuum, and can be reused directly without further purification. The recovered catalyst was used
in the next run, and almost consistent activity was observed for next eight consecutive cycles
(Figure 2). In addition, a SEM observation of the recovered catalyst after eighth cycles was made,
and there was obvious change in the morphology and the size in comparison to the fresh catalyst
(Figure 1C). And the content of niobium in the reaction mixture was < 2 ppm determined by ICP
analysis. These results revealed that the decrease in catalytic activity of SiO2-tpy-Nb in subsequent
runs. Encouraged by the excellent durability of catalyst, we applied it in the continuous flow

ACCEPTED MANUSCRIPT
Page 9 of 14
system to investigate the scalability of this method. The catalyst SiO2-tpy-Nb packed-bed was
assembled which would provide efficient mixing and enhanced mass and heat transfer to improve
the reaction efficiency. The model reaction was employed in the packed-bed reactor, and 82%
yield was obtained for a 30 min residence time (see Supporting Information for details).
100
80
60
80
71
78
76
89
87
84
88
40
20
0
1
2
3
4
5
6
7
8
Cycle
Figure 2 Recycling experiment
A hot filtration test was conducted to figure out whether the catalytic process involved
o
in the homogeneous fashion. When the model reaction mixture was stirred at 110 C for 6
h (yield 59%), the catalyst was then removed by filtration at the reaction temperature. The
filtrate was reacted for an additional 12 h. The reaction continued, although the conversion
did not reach the level obtained in the normal manner, which means that at least a part of
catalytic activity of the catalyst was assigned to a homogeneous way. And this can be
explained by a "release and recapture" mechanism as described in previous literature [35].
CONCLUSIONS
In conclusion, we have developed a novel and efficient heterogeneous terpyridine
niobium catalyst for the preparation of various N-substituted phthalimides from o-phthalic
acids or anhydrides with amines. And this method provides a convenient access to
5-methyl-2-(prop-2-yn-1-yl)isoindoline-1,3-dione in high yield, which has potential
anticancer bioactivities and
important application in novel polymeric materials.
Meanwhile, the catalyst exhibits highly stability and recyclability for eight cycles without a
significant loss of its catalytic activity, which make this procedure more environmentally
acceptable. In addition, the application of the catalyst SiO2-tpy-Nb in continuous flow
system demonstrates its potential in industrialization.

ACCEPTED MANUSCRIPT
Page 10 of 14
ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China (21502090
and 21522604), Natural Science Foundation of Jiangsu Province (BK20150942 and
BK20150031) and the National Key Basic Research Program of China (2012CB725204).
We also thank the financial support from Top-notch Academic Programs Project of Jiangsu
Higher Education Institutions (TAPP).
REFERENCES
[1] P. Ahuja, A. Husain, N. Siddiqui, Med. Chem. Res. 23 (2014) 4085–4098.
[2] D. Dunn, J. Husten, L. D. Aimone, M. A. Ator, S. Chatterjee, Chem. Biol. Drug Des. 82
(2013) 348–350.
[3] A. M. Al-Azzawi, M. S. A. Al-Razzak, Int. J. Res. Pharm. Chem. 3 (2013) 682–690.
[4] U. Sharma, P. Kumar, N. Kumar, B. Singh, Mini Rev. Med. Chem. 10 (2010) 678–704.
[5] J.-P. Sun, A. D. Hendsbee, A. F. Eftaiha, C. Macaulay, L. R. Rutledge, G. C. Welch, I. G.
Hill, J. Mater. Chem. C 2 (2014) 2612–2621.
[6] H. Nakayama, J.-i. Nishida, N. Takada, H. Sato, Y. Yamashita, Chem. Mater. 24 (2012)
671–676.
[7] M. Sani, G. Fossati, F. Huguenot, M. Zanda, Angew. Chem. Int. Ed. 46 (2007)
3526–3529.
[8] C. J. Perry, Z. Parveen, J. Chem. Soc. Perkin Trans. 2 2001 512–521.
[9] A. A. Abdel-Hafez, Arch. Pharm. Res. 27 (2004) 495–501.
[10] M. M. Heravi, R. H. Shoar, L. Pedram, J. Mol. Catal. A: Chem. 231 (2005) 89–91.
[11] B. Martin, H. Sekljic, C. Chassaing, Org. Lett. 5 (2003) 1851–1853.
[12] X. Wu, S. Oschatz, M. Sharif, A. Flader, L. Krey, M. Beller, P. Langer, Adv. Synth.
Catal. 355 (2013) 3581–3585.
[13] X. Yan, K. Fang, H. Liu, C. Xi, Chem. Commun. 49 (2013) 10650–10652.
[14] X.-Y. Shi, A. Renzetti, S. Kundu, C.-J. Li, Adv. Synth. Catal. 356 (2014) 723–728.
[15] K. Nakajima, Y. Baba, R. Noma, M. Kitano, J. N. Kondo, S. Hayashi, M. Hara, J. Am.
Chem. Soc. 133 (2011) 4224–4227.

ACCEPTED MANUSCRIPT
Page 11 of 14
[16] K. Nakajima, R. Noma, M. Kitano, M. Hara, J. Phys. Chem. C 117 (2013) 16028–16033.
[17] Y. Wang, F. Wang, Q. Song, Q. Xin, S. Xu, J. Xu, J. Am. Chem. Soc. 135 (2013)
1506–1515.
[18] Md. A. Ali, S. M. A. H. Siddiki, K. Kon, J. Hasegawa, K. Shimizu, Chem. Eur. J. 20
(2014) 14256–14260.
[19] Md. A. Ali, S. K. Moromi, A. S. Touchy, K. Shimizu, ChemCatChem 8 (2016) 891–894.
[20] V. Polshettiwar, C. Len, A. Fihri, Coord. Chem. Rev. 253 (2009) 2599–2626.
[21] Q. Zhao, F. Li, C. Huang, Chem. Soc. Rev. 39 (2010) 3007–3030.
[22] D.-L. Ma, V. P.-Y. Ma, D. S.-H. Chan, K.-H. Leung, H.-Z. He, C.-H. Leung, Coord.
Chem. Rev. 256 (2012) 3087–3113.
[23] H. Woo, S. Cho, Y. Han, W.-S. Chae, D.-R. Ahn, Y. You, W. Nam, J. Am. Chem. Soc.
135 (2013) 4771–4787.
[24] Z.-L. Gong, Y.-W. Zhong, Organometallics, 32 (2013) 7495–7502.
[25] A. Joshi-Pangu, M. Ganesh, M. R. Biscoe, Org. Lett. 13 (2011) 1218–1121.
[26] G. D. Jones, C. McFarland, T. J. Anderson, D. A. Vicic, Chem. Commun. 41 (2005)
4211–4213.
[27] P. Liu, C.-Y. Zhou, S. Xiang, C.-M. Che, Chem. Commun. 46 (2010) 2739–2741.
[28] M. M. Amini, A. Feiz, M. Dabiri, A. Bazgir, Appl. Organometal. Chem. 28 (2014)
86–90.
[29] J. R. Naber, S. L. Buchwald, Angew. Chem. Int. Ed. 49 (2010) 9469–9474.
[30] M. Chen, S. Ichikawa, S. L. Buchwald, Angew. Chem. Int. Ed. 54 (2015) 263–266.
[31] D.-W. Yoo, S.-K. Yoo, C. Kim, J.-K. Lee, J. Chem. Soc. Dalton Trans. 2002,
3931–3932.
[32] K. R. Senwar, P. Sharma, S. Nekkanti, M. Sathish, A. Kamal, B. Sridhar, N.
Shankaraiah, New J. Chem. 39 (2015) 3973–3981.
[33] D. G. Hamilton, L. Prodi, N. Feeder, J. K. M. Sander, J. Chem. Soc. Perkin Trans. 1 (1999)
1057–1065.
[34] Q. Zhang, D. G. Hamilton, N. Feeder, S. J. Teat, J. M. Goodman, J. K. M. Sanders, New J.
Chem. 23 (1999) 897–903.

ACCEPTED MANUSCRIPT
Page 12 of 14
[35] D. Zim, S. M. Nobre, A. L. Monterio, J. Mol. Catal. A Chem. 287 (2008) 16–23.

ACCEPTED MANUSCRIPT
Page 13 of 14
An efficient synthesis of N-substituted phthalimides using SiO2-tpy-Nb as heterogeneous and
reusable catalyst
L. Wan,a,c X. N. Sun,a S. J. Shi,a J. W. Zhang,a X. Li,a Z. J. Lia and K. Guo*a,b,c
a College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu
South Road, Nanjing (P. R. China)
b State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University,
5 Xinmofan Road, Nanjing (P. R. China)
c Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), 30 Puzhu
South Road, Nanjing (P. R. China)
E-mail: guok@njtech.edu.cn
Graphical abstract
A novel and efficient heterogeneous catalyst SiO2-tpy-Nb was developed to prepare
N-substituted phthalimides from o-phthalic acids or anhydrides with amines in good to excellent
yields.

ACCEPTED MANUSCRIPT
Page 14 of 14
Highlights
1. A novel heterogeneous catalyst SiO2-tpy-Nb was developed to prepare N-substituted
phthalimides.
2. The catalyst was stable and recoverable for eight cycles without significant loss in its activity.
3. The catalyst is applicable in continuous flow which indicates its utilization in industry.