PPh3/I2/HCOOH: An efficient CO source for the synthesis of phthalimides

Article abstract of DOI:10.1016/j.tet.2019.01.023

A straightforward and general method has been developed for the synthesis of phthalimide derivatives from 2-iodobenzamides and PPh₃/I₂/HCOOH in the presence of a catalytic amount of Pd(OAc)₂. The reaction results demonstrate that PPh₃/I₂/HCOOH is a facile, efficient and safe CO source. The whole process is carried out in toluene at 80 °C and furnishes the desired products in good to excellent yields.

Full text of DOI:10.1016/j.tet.2019.01.023

Accepted Manuscript
PPh /I /HCOOH: An efficient CO source for the synthesis of phthalimides
3 2
Yingying Wang, Yang Zhou, Min Lei, Jinjun Hou, Qinghao Jin, Dean Guo, Wanying
Wu
PII:
S0040-4020(19)30051-1
https://doi.org/10.1016/j.tet.2019.01.023
TET 30075
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 November 2018
Revised Date: 9 January 2019
Accepted Date: 11 January 2019
Please cite this article as: Wang Y, Zhou Y, Lei M, Hou J, Jin Q, Guo D, Wu W, PPh /I /HCOOH: An
3 2
efficient CO source for the synthesis of phthalimides, Tetrahedron (2019), doi: https://doi.org/10.1016/
j.tet.2019.01.023.
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ACCEPTED MANUSCRIPT
Graphical Abstract
PPh3/I2/HCOOH: an efficient CO source for
the synthesis of phthalimides
Leave this area blank for abstract info.
Yingying Wang, Yang Zhou, Min Lei, Jinjun Hou, Qinghao Jin, Dean Guo, Wanying Wu

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
PPh3/I2/HCOOH: an efficient CO source for the synthesis of phthalimides
Yingying Wang a,b,1, Yang Zhou a,b,1, Min Lei a,b, , Jinjun Hou a,b, Qinghao Jin a,b, Dean Guo a,b and
Wanying Wua,b,
aShanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology,
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
bUniversity of Chinese Academy of Sciences, Beijing 100049, PR China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A straightforward and general method has been developed for the synthesis of phthalimide
derivatives from 2-iodobenzamides and PPh3/I2/HCOOH in the presence of a catalytic amount of
Pd(OAc)2. The reaction results demonstrate that PPh3/I2/HCOOH is a facile, efficient and safe
CO source. The whole process is carried out in toluene at 80 oC and furnishes the desired
products in good to excellent yields.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Phthalimide
PPh3/I2/HCOOH
2-Iodobenzamide
Pd(OAc)2
CO source
1. Introduction
or toxic reagents. For example, Fe(CO)5 is highly volatile, tough
handle and very toxic. Therefore, searching for more facile and
practical synthetic routes to synthesis of phthalimides is still
highly desirable work.
Phthalimides are a category of important compounds because
of their significant biological activities as well as wide-ranging
utility in organic synthesis.1 For example, the Gabriel synthesis, a
famous named reaction first reported by S. Gabriel in 1887,2 is an
efficient method for the synthesis of primary amines from alkyl
halides and phthalimide.3 In recent years, phthalimides also apply
in synthesis of dyestuff,4 pesticide,5 and rubber.6 Due to the
importance mentioned above, the synthesis of phthalimides
towards milder reaction conditions and improved yields
receives widespread attention.
CO is an important C1 source which applies in industrial
manufacture widely. However, laboratorial utilization of gaseous
CO suffers from storage, transportation, handling as well as
safety regulations. Recently, although several C1 sources are
reported, such as N-formylsaccharin,14 9-methylfluorene-9-
carbonyl chloride,15 acetic formic anhydride,16 Fe(CO)5,17 etc,18
these reagents have one or more drawbacks in using. Therefore,
there has been considerable interest to explore more facile and
practical agent as C1 source in organic synthesis.
Recently, methods have been discovered to synthesis of
phthalimides: (a) o-phthalic anhydride with nitrogen source;7 (b)
phthalic acid with nitrogen source;8 (c) hydration of
phthalonitrile;9 (d) 2-iodobenzoic acid with DMF/POCl3;10 (e)
1,2-diiodobenzene with DMF/POCl3;11 (f) coupling with
CO;12 (g) and other methods.13 Although, a number of modified
methods under improved conditions have been reported, many of
them suffer from drawbacks such as unsatisfactory yields, high
During the course of our studies, we found PPh3/I2/HCOOH
could release CO efficiently and rapidly (Scheme 1). This result
inspired us that PPh3/I2/HCOOH might be as CO precursor used
in organic synthesis. In order to examine our idea, we carried out
the model reaction of 2-iodobenzamide and PPh3/I2/HCOOH in
o
the presence of Pd(OAc)2 in toluene at 80 C for 2 h. To our
delight that the desired product phthalimide was obtained in 78%
temperatures, and long reaction times, and the use of expensive
———
1 These three authors attributed equally to this work.
Corresponding author.
E-mail address: mlei@simm.ac.cn (M. Lei)
Corresponding author.
E-mail address: wanyingwu@simm.ac.cn (W. Wu)

2
Tetrahedron
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Table 1. Screen of solventa
yield (Scheme 2). Hence, we would like to report a simple,
efficient and practical method for the synthesis of phthalimides
using PPh3/I2/HCOOH as CO source.
Yield (%)b
Entry
Solvent
1a
2
2a
96
90
28
32
31
21
3a
2
Scheme 1. PPh3/I2/HCOOH is an efficient CO precursor.
1
2
3
4
5
6
DMSO
DMF
2
8
MeCN
THF
36
14
1
36
54
68
78
EtOAc
toluene
1
aReaction conditions: 1a (1 mmol), HCOOH (4 mmol, 4 equiv), I2 (1.3 mmol,
1.3 equiv), PPh3 (1.3 mmol, 1.3 equiv), Pd(OAc)2 (0.03 mmol, 3 mol%), Et3N
(6 mmol, 6 equiv), solvent (4 mL), 80 °C for 2 h.
Scheme 2. Synthesis of phthalimide using PPh3/I2/HCOOH
as CO precursor.
bYields were determined by LC-MS.
2. Results and Discussion
Table 2. Screen of Pd catalysta
For further improve the yields of this synthetic reaction, the
model reaction was carried out under different conditions.
Initially, to investigate the solvent effects, the reaction was
carried out in different solvents, and the results are summarized
in Table 1. De-iodo product 2a was obtained in 96% and 90%
yields in DMSO and DMF as slolvents, respectively. While the
desired product 3a was obtained with low yields (2% and 8%
yields, respectively). These results indicated that high polar
solvents were not suitable for this model reaction (Table 1,
entries 1 and 2). Moderate yields of 3a (36–68%) were obtained
when the reaction carried out in MeCN, THF, EtOAc (Table 1,
entries 3–5). In all examined solvents, toluene showed the best
solvent effect, and the desired product 3a was obtained in 78%
yield (Table 1, entry 6). Hence, toluene was chosen as the solvent
for all further reaction.
Yield (%)b
Entry
[Pd] (mol %)
1a
2a
3a
1
2
3
4
5
6
7
8
9
23
2
2
14
1
75
84
88
88
92
93
95
97
89
PdSO4 (3)
Pd(TFA)2 (3)
Pd(PPh3)4 (3)
PdCl2 (3)
11
9
3
Pd(OAc)2 (3)
Pd(OAc)2 (2.5)
Pd(OAc)2 (2)
Pd(OAc)2 (1.5)
Pd(OAc)2 (1)
3
5
Then, the other factors, such as equivalences of HCOOH and
Et3N, were also investigated, and the results showed that 2
equivalences of HCOOH and 3 equivalences of Et3N were more
suitable (see Tables S2 and S3 in the SI). In addition, Pd catalysts
were also examined and the results are summarized in Table 2.
3
4
1
4
1
2
10
1
aReaction conditions: 1a (1 mmol), HCOOH (2 mmol, 2 equiv), I2 (1.3 mmol,
1.3 equiv), PPh3 (1.3 mmol, 1.3 equiv), Pd(OAc)2, Et3N (3 mmol, 3 equiv),
toluene (4 mL), 80 °C for 2 h.
Among the Pd catalysts screened, Pd(OAc)2 showed excellent
activity in terms of yield (88%) in producing the required product
(Table 2, entry 5). Next, we optimized the amount of Pd(OAc)2
in the model reaction, and the optimum amount of Pd(OAc)2 was
found to be 1.5 mol % (Table 2, entry 8).
bYields were determined by LC-MS.
Furthermore, the amount of I2 and PPh3 was also optimized
(see Table S5 in the SI). After extensive experimentation (see
Tables S1-S5 in the SI), the optimal condition was established as
HCOOH (2 equiv), Et3N (3 equiv), Pd(OAc)2 (1.5 mol %), I2 (1.1
equiv), PPh3 (1.3 equiv) in toluene at 80 C for 2 h. Moreover,
92% isolated yield of 3a was obtained under the optimal
In order to gauge the scope of the conditions, a series of 2-
iodobenzamide derivative were examined under the optimized
conditions (Table 3). At first, a series of N-alkyl, N-benzyl and
N-aryl substituted 2-iodobenzamides were synthesized as starting
materials. As shown in Table 3, except for 3f (47%), all the N-
alkyl and N-benzyl substituted substrates could react smoothly to
obtain the desired products 3 in good yields (84–95%). Most
importantly, aryl carrying either electron-donating or electron-
withdrawing substituents reacted efficiently giving excellent
yields (83–95%). Heteroaryl substrate was also synthesized and
used for the reaction, and desired product 3t was obtained in 83%
yield. Furthermore, 2-iodo-5-methylbenzamide and 4-chloro-2-
iodobenzamide were also examined under the optimized
conditions to obtain the desired products 3w and 3x in 95% and
o
condition.

3
75% yields, respectively. Obviously, the yield of 3x was much
lower than 3w under similar reaction conditions in that de-chloro
product 3a was formed when using 4-chloro-2-iodobenzamide as
substrate. Moreover, 1d was selected as substrate to synthesis
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of 3d under gram-scale, and desired product 3d was obtained in
85% yield.
Table 3. Synthesis of phthalimide derivativesa,b
I2 (1.1 equiv)
PPh3 (1.3 equiv)
Pd(OAc)2 (1.5 mol%)
O
O
R2
+
R1
N
HCOOH
N R2
R1
H
Et3N (3 equiv)
toluene
I
O
3a-x
80 oC, 2 h
1a-x
O
O
N
O
O
O
NH
N
N
O
O
O
3a, 92%
3b, 95%
3c, 95%
3d, 94%
O
O
O
N
O
N
N
N
O
O
O
O
3f, 47%c
3e, 92%
3g, 87%
3h, 84%
O
N
O
O
N
O
N
O
N
O
O
O
3i, 88%
3j, 92%
3k, 94%
3l, 95%
O
O
N
O
N
O
O
O
N
O
N
O
O
O
O
3m, 94%
3n, 94%
3o, 94%
3p, 94%
O
N
O
N
O
O
N
Cl
CN
N
COOEt
N
O
O
O
O
3q, 91%
3r, 95%
3s, 87%
3t, 83%
O
N
O
O
O
N
O
O
NH
NH
Cl
O
O
O
O
O
O
3u, 94%
3v, 93%
3w, 95%
3x, 75%
aReaction conditions: 1a (1 mmol), HCOOH (2 mmol, 2 equiv), I2 (1.1 mmol, 1.1 equiv), PPh3 (1.3 mmol, 1.3 equiv), Pd(OAc)2 (1.5 mol %), Et3N (3 mmol, 3
equiv), toluene (4 mL), 80 °C for 2 h.

4
Tetrahedron
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bIsolated Yields.
cThe reaction proceeded for 3 h.
Based on the experimental results and previous reports, a
plausible reaction mechanism was proposed (Scheme 4).19 PdII
was reduced by PPh3 to form Pd0 complex A.19 Through a
oxidative addition process of aryl iodide to Pd0 to form PdII
complex B. Then, HI was released under the action of base to
form C. At same time, I2 and PPh3 formed complex D, which
promated the release of CO from formic acid. Then, CO was
captured by palladium intermediate C to form E. Upon reduction
elimination, complex E gave the final product 3 and Pd0 that
launched another catalytic cycle.
For the further study why the yield of 3f was much lower than
other cases, we carried out the reaction of N-(tert-butyl)-2-
iodobenzamide (1f) and PPh3/I2/HCOOH under the optimized
conditions. The reaction used LC-MS to track and monitor. The
result showed that a main by-product with m/z 222.7 [M + H]+
was formed. Then, the by-product (4) was isolated and the
structure was established by NMR (Scheme 3). The main reason
for phenomenon might result from large steric hindrance of tert-
butyl which effected the intramolecular cyclization.
Scheme 4. Plausible mechanism for the formation of phthalimides.
methodology are: (a) operational simplicity, (b) short reaction
times, (c) high yields of products, and (d) the use of relatively
non-toxic reagents. The present study provided
supplement for the synthesis of phthalimides.
a useful
4. Experimental section
4.1. General information
Scheme 3. Reaction of 1f with PPh3/I2/HCOOH.
All reactions were performed in flame-dried glassware using
sealed tube. Liquids and solutions were transferred with syringes.
All solvents and chemical reagents were obtained from
3. Conclusion
In conclusion, we have developed a simple and efficient
method for the synthesis of phthalimide derivatives from from 2-
iodobenzamides and PPh3/I2/HCOOH in the presence of a
catalytic amount of Pd(OAc)2. The main advantages of this
1
commercial sources and used without further purifications. H
and 13C NMR spectra were recorded with tetramethylsilane as an
internal reference at 400 MHz and 101 MHz, respectively.

5
4.2.7. N-Cyclopentylphthalimide (3g).
Spectra were referenced to the residual solvent peak of CDCl3 or
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Yield: 187 mg (87%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.84–7.74 (m, 2H), 7.69–7.66 (m, 2H), 4.61 (p, J=8.4
Hz, 1H), 2.13–2.01 (m, 2H), 1.98–1.88 (m, 4H), 1.66–1.61 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 168.40, 133.72, 132.08,
122.92, 50.90, 29.56, 25.09; MS (ESI) m/z 216.6 [M+H]+.
DMSO-d6 unless otherwise noted. Low and high-resolution mass
spectra were obtained in the ESI mode. Flash column
chromatography on silica gel (200-300 mesh) was used for the
routine purification of reaction products. The column output was
monitored by analytical thin-layer chromatography (TLC) on
silica gel (100-200 mesh) precoated on glass plates (15 x 50
mm), and spots were visualized by ultraviolet light at 254 or 365
nm. Melting points were recorded on a WRS-1B melting point
apparatus and are uncorrected. Commercially available chemicals
were obtained from Acros Organics, Strem Chemicals, Alfa
Aesar, Adamas-beta, J&K and TCI.
4.2.8. N-Cyclohexylphthalimide (3h).
Yield: 192 mg (84%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.82–7.78 (m, 2H), 7.70–7.66 (m, 2H), 4.10 (tt, J=12.4,
4.0 Hz, 1H), 2.20 (qd, J=12.4, 3.2 Hz, 2H), 1.90–1.83 (m, 2H),
1.74–1.67 (m, 3H), 1.40–1.24 (m, 3H); 13C NMR (101 MHz,
CDCl3) δ 168.58, 133.85, 132.22, 123.12, 51.04, 30.01, 26.16,
25.26; MS (ESI) m/z 230.7 [M+H]+.
4.2. Experimental procedure for the synthesis of compound
3a-x
4.2.9. N-Benzylphthalimide (3i).
Yield: 209 mg (88%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.86–7.83 (m, 2H), 7.72–7.69 (m, 2H), 7.49–7.41 (m,
2H), 7.35–7.32 (m, 2H), 7.30–7.28 (m, 1H), 4.87 (s, 2H); 13C
NMR (101 MHz, CDCl3) δ 168.04, 136.44, 134.01, 132.17,
128.72, 128.65, 127.86, 123.36, 41.65; MS (ESI) m/z 238.9
[M+H]+.
PPh3 (1.3 mmol, 1.3 equiv), I2 (1.3 mmol, 1.3 equiv) and
toluene (4 mL) were added to a 20 mL test tube equipped with a
stir bar, which was stirred for 10 min at room temperature. Then
2-iodo-benzamide (1) (1 mmol), Pd(OAc)2 (0.015 mmol, 1.5
mol%), and Et3N (3.0 mmol, 3.0 equiv) were added into the
solution. At last, HCOOH (2 mmol, 2 equiv) was added, and the
tube was immediately sealed and stirred at 80 oC for 2 h (3 h for
1f). After completion of the reaction, the mixture was cooled to
room temperature, and diluted with DCM (20 mL). The solid was
removed by filter, and the filtrate was washed with water (20
mL) and brine (20 mL). The organic layer was dried over
Na2SO4, filtered, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel
(petroleum ether/acetone = 8/1, v/v) to afford the product 3a-x.
4.2.10. N-Phenylphthalimide (3j).
Yield: 205 mg (92%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.97–7.95 (m, 2H), 7.80–7.78 (m, 2H), 7.54–7.38 (m,
5H); 13C NMR (101 MHz, CDCl3) δ 167.38, 134.50, 131.88,
131.81, 129.22, 128.21, 126.69, 123.86; MS (ESI) m/z 224.7
[M+H]+.
4.2.11. N-(o-Tolyl)phthalimide (3k).
Yield: 223 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.98–7.94 (m, 2H), 7.81–7.77 (m, 2H), 7.40–7.30 (m,
3H), 7.21 (d, J=7.6 Hz, 1H), 2.22 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 167.47, 136.68, 134.44, 132.17, 131.29, 130.73,
129.58, 128.86, 127.01, 123.90, 18.18; MS (ESI) m/z 238.7
[M+H]+.
4.2.1. Phthalimide (3a).
o
1
Yield: 135 mg (92%); white solid; mp: 244.4–246.4 C; H
NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 7.81–7.80 (m, 4H);
13C NMR (101 MHz, DMSO-d6) δ 169.19, 134.28, 132.59,
122.89; MS (ESI) m/z 148.6 [M+H]+.
4.2.2. N-Methylphthalimide (3b).
Yield: 153 mg (95%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.84–7.82 (m, 2H), 7.70–7.68 (m, 2H), 3.17 (s, 3H) ;
13C NMR (101 MHz, CDCl3) δ 168.58, 133.98, 132.33, 123.27,
24.05; MS (ESI) m/z 162.6 [M+H]+.
4.2.12. N-(m-Tolyl)phthalimide (3l).
Yield: 225 mg (95%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.93–791 (m, 2H), 7.77–7.75 (m, 2H), 7.39 (t, J=7.6
Hz, 1H), 7.26–7.15 (m, 3H), 2.42 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 167.36, 139.12, 134.37, 131.81, 131.58, 129.04,
128.95, 127.29, 123.78, 123.69, 21.43; MS (ESI) m/z 238.8
[M+H]+.
4.2.3. N-Ethylphthalimide (3c).
Yield: 167 mg (95%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.83–7.81 (m, 2H), 7.70–7.68 (m, 2H), 3.73 (q, J=7.2
Hz, 2H), 1.26 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.15,
133.80, 132.21, 123.07, 32.87, 13.94; MS (ESI) m/z 176.4
[M+H]+.
4.2.13. N-(p-Tolyl)phthalimide (3m).
Yield: 223 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.95–7.90 (m, 2H), 7.78–7.74 (m, 2H), 7.31 (s, 4H),
2.41 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.43, 138.17,
134.35, 131.86, 129.80, 129.06, 126.50, 123.69, 21.26; MS (ESI)
m/z 238.8 [M+H]+.
4.2.4. N-Propylphthalimide (3d).
Yield: 178 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.81–7.79 (m, 2H), 7.68–7.66 (m, 2H), 3.62 (t, J=7.2
Hz, 2H), 1.67 (h, J=7.2 Hz, 2H), 0.91 (t, J=7.2 Hz, 3H); 13C
NMR (101 MHz, CDCl3) δ 168.41, 133.86, 132.17, 123.14,
39.61, 21.96, 11.38; MS (ESI) m/z 190.6 [M+H]+.
4.2.14. N-(2-Methoxyphenyl)phthalimide (3n).
Yield: 238 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.96–7.91 (m, 2H), 7.79–7.74 (m, 2H), 7.48–7.39 (m,
1H), 7.26 (dd, J=7.6, 1.6 Hz, 1H), 7.13–6.97 (m, 2H), 3.79 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 167.41, 155.49, 134.17,
132.30, 130.72, 130.04, 123.69, 120.91, 120.35, 112.22, 55.88;
MS (ESI) m/z 254.7 [M+H]+.
4.2.5. N-Isopropylphthalimide (3e).
Yield: 173 mg (92%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.81–7.79 (m, 2H), 7.69–7.68 (m, 2H), 4.59–4.44 (m,
1H), 1.48 (dd, J=7.2, 0.8 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ
168.34, 133.77, 132.13, 122.98, 43.00, 20.15; MS (ESI) m/z
189.5 [M+H]+.
4.2.15. N-(3-Methoxyphenyl)phthalimide (3o).
Yield: 238 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.96–7.93 (m, 2H), 7.80–7.77 (m, 2H), 7.41 (t, J=8.0
Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 7.00–6.90 (m, 2H), 3.83 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 167.33, 160.17, 134.52, 132.79,
131.87, 129.91, 123.87, 118.99, 114.24, 112.49, 55.56; MS (ESI)
m/z 254.6 [M+H]+.
4.2.6. N-(tert-Butyl)phthalimide (3f).
Yield: 95 mg (47%); white solid; 1H NMR (400 MHz, CDCl3)
δ 7.76–7.73 (m, 2H), 7.67–7.62 (m, 2H), 1.68 (s, 9H) ); 13C NMR
(101 MHz, CDCl3) δ 169.76, 133.75, 132.26, 122.66, 57.93,
29.20; MS (ESI) m/z 204.5 [M+H]+.

6
Tetrahedron
4.2.16. N-(4-Methoxyphenyl) phthalimide (3p).
134.61, 134.05, 131.16, 124.69, 122.98; MS (ESI) m/z 180.5 [M–
ACCEPTED MANUSCRIPT
H]–; HRMS (ESI) calcd for C8H5ClNO2 [M+H]+ 182.0003, found
182.0006.
Yield: 238 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.91–7.88 (m, 2H), 7.76–7.73 (m, 2H), 7.36–7.29 (m,
2H), 7.01–6.99 (m, 2H), 3.82 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 167.63, 159.28, 134.38, 131.83, 128.01, 124.29,
123.71, 114.51, 55.57; MS (ESI) m/z 254.4 [M+H]+.
4.2.25. 2-(tert-Butylcarbamoyl)benzoic acid (4).
o
1
Yield: 90 mg (41%); white solid; mp: 158.1–158.6 C ; H
NMR (400 MHz, DMSO-d6) δ 12.90 (brs, 1H), 7.84 (s, 1H), 7.79
(d, J=7.2 Hz, 1H), 7.54 (t, J=7.2 Hz, 1H), 7.47 (t, J=7.2 Hz, 1H),
7.37 (d, J=7.2 Hz, 1H), 1.38 (s, 9H); 13C NMR (101 MHz,
DMSO-d6) δ 168.52, 168.13, 139.98, 131.23, 130.40, 129.28,
128.67, 127.90, 50.76, 28.63; MS (ESI) m/z 222.7 [M+H]+;
HRMS (ESI) calcd for C12H16NO3 [M+H]+ 222.1125, found
222.1125.
4.2.17. N-(4-Chlorophenyl) phthalimide (3q).
Yield: 234 mg (91%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.97–7.93 (m, 2H), 7.82–7.78 (m, 2H), 7.48–7.46 (m,
2H), 7.42–7.40 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 167.05,
134.66, 133.84, 131.64, 130.27, 129.37, 127.75, 123.93; MS
(ESI) m/z 258.8 [M+H]+.
4.2.18. N-(4-Cyanophenyl)phthalimide (3r).
Yield: 236 mg (95%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.97–7.95 (m, 2H), 7.84–7.81 (m, 2H), 7.78 (d, J=8.4
Hz, 2H), 7.67 (d, J=8.4 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ
166.54, 135.98, 135.03, 133.02, 131.40, 126.55, 124.19, 118.35,
111.34; MS (ESI) m/z 249.9 [M+H]+.
Acknowledgments
This research was supported by Special Fund for Strategic
Pilot
Technology
Chinese
Academy
of
Sciences
(XDA12040303).
4.2.19. Ethyl 4-(1,3-dioxoisoindolin-2-yl)benzoate
(3s).
References and notes
Yield: 257 mg (87%); white solid; 1H NMR (400 MHz,
CDCl3) δ 8.14 (d, J=8.6 Hz, 2H), 7.91 (dd, J=5.4, 3.1 Hz, 2H),
7.77 (dt, J=5.4, 3.4 Hz, 2H), 7.56 (d, J=8.6 Hz, 2H), 4.37 (q,
J=7.1 Hz, 2H), 1.38 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 166.73, 165.75, 135.76, 134.63, 131.49, 130.28,
129.53, 125.87, 123.83, 61.17, 14.33; MS (ESI) m/z 296.6
[M+H]+.
1. (a) Sharma U, Kumar P, Kumar N, Singh B. Mini-Rev Med Chem.
2010;10:678;
(b) Abdel-Hafez AA. Arch Pharmacal Res. 2004;27:495;
(c) Meng X-B, Han D, Zhang S-N, Guo W, Cui JR, Li Z-J,
Carbohydr Res. 2007;342:1169;
(d) Shiri A, Khoramabadi-zad A. Synthesis. 2009;41:2797;
(e) Cui X, Surkus A-E, Junge K, Topf C, Radnik J, Kreyenschulte
C, Beller M. Nat Commum. 2016;7:11326;
4.2.20. N-(4-Pyridyl)phthalimide (3t).
(f) Moriyama K, Ishida K, Togo H. Chem Commun.
2012;48:8574.
Yield: 186 mg (83%); white solid; mp: 247.2–248.3 C ; 1H
o
2. Gabriel S. Ber. 1887;20:2224.
NMR (400 MHz, DMSO-d6) δ 8.74 (d, J=5.4 Hz, 2H), 8.02–8.00
(m, 2H), 7.95–7.93 (m, 2H), 7.59 (d, J=5.4 Hz, 2H) ; 13C NMR
(101 MHz, DMSO-d6) δ 166.19, 150.45, 139.52, 135.01, 131.38,
123.69, 120.64; MS (ESI) m/z 225.7 [M+H]+; HRMS (ESI) calcd
for C13H9N2O2 [M+H]+ 225.0659, found225.0655.
3. (a) Matsuoka K, Kohzu T, Hakumura T, Koyama T, Hatano K,
Terunuma D. Tetrahedron Lett. 2009;50: 2593;
(b) Nigh WG. J Chem Educ. 1951;28:294;
(c) Khan MN, J Org Chem. 1996;61:8063.
4. (a) Choi J-H, Jeon J-M, Kim M-H, Towns AD, Yoon C. Color
Technol. 2008;124:92;
(b) Choi J-h, Choi J-y, Lee H-y, Towns AD, Yoon C. Color
Technol. 2008;124:364.
5. Oikawa N, Nakagawa Y, Nishimura K, Ueno T, Fujita T. Pestic
Biochem Phys. 1994;48:135.
4.2.21. Methyl 2-(1,3-dioxoisoindolin-2-
yl)propanoate (3u).
Yield: 229 mg (94%); white solid; 1H NMR (400 MHz,
CDCl3) δ 7.68–7.63 (m, 2H), 7.59–7.54 (m, 2H), 3.81 (t, J=7.2
Hz, 2H), 3.51 (s, 3H), 2.57 (t, J=7.2 Hz, 2H); 13C NMR (101
MHz, CDCl3) δ 171.29, 168.04, 134.12, 132.11, 123.42, 51.99,
33.85, 32.87; MS (ESI) m/z 234.4 [M+H]+.
6. Hu Z, Li S. Int J Chem. 2010;2:213.
7. (a) Ma Y, Stivala CE, Wright AM, Hayton T, Liang J, Keresztes I,
Lobkovsky E, Collum DB, Zakarian A. J Am Chem Soc.
2013;135:16853;
(b) Liu Z, Yuan Q, Wang W. Amino Acids. 2009;36:71;
(c) Kumar CSC, Loh W-S, Chandraju S, Win Y-F, Tan WK, Quah
CK, Fun H-K. Plos One. 2015;10:e0119440.
8. Ali A, Siddiki SMAH, Kon K, Hasegawa J, Shimizu K. Chem-Eur
J. 2014;20:14256.
9. (a) Verma PK, Sharma U, Bala M, Kumar N, Singh B. RSC Adv.
2013;3:895;
(b) Verma PK, Kumar N, Sharma U, Bala M, Kumar V, Singh B.
Synth Commum. 2013;43:5867.
10. Sawant DN, Wagh YS, Bhatte KD, Bhanage BM. Eur J Org
Chem. 2011;33:6719.
4.2.22. (S)-N-Phthaloylphenylglycine methyl ester
(3v).
o
1
Yield: 275 mg (93%); white solid; mp: 107.9–110.1 C ; H
NMR (400 MHz, CDCl3) δ 7.78–7.76 (m, 2H), 7.62–7.60 (m,
2H), 7.59–7.53 (m, 2H), 7.39–7.27 (m, 3H), 6.05 (s, 1H), 3.78 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 167.99, 166.50, 134.06,
133.77, 131.18, 129.24, 128.13, 128.06, 123.06, 77.16, 55.29,
52.53; MS (ESI) m/z 296.7 [M+H]+; HRMS (ESI) calcd for
C17H14NO4 [M+H]+ 296.0917, found 296.0921.
11. Sawant DN, Wagh YS, Tambade PJ, Bhatte KD, Bhanage BM.
Adv Synth Catal. 2011;353:781.
12. (a) Uozumi Y, Kawasaki N, Mori E, Mori M, Shibasak M. J Am
Chem Soc. 1989;111:3725;
4.2.23. 4-Methylphtalimide (3w).
Yield: 151 mg (95%); white solid; 1H NMR (400 MHz,
DMSO-d6) δ 11.22 (s, 1H), 7.73–7.53 (m, 3H), 2.48 (s, 3H); 13C
NMR (101 MHz, DMSO-d6) δ 169.26, 169.17, 145.13, 134.65,
132.96, 129.99, 123.28, 122.80, 21.32; MS (ESI) m/z 160.6 [M–
H]–.
(b) w
Wu X, Mahalingam AK, Wan Y, Alterman M. Tetrahedron Lett.
2004;45:4635.
13. (a) Tkachuk VA, Omelchenko IV, Hordiyenko OV. Synlett.
2017;28:851;
(b) Song B, Wang S, Su C, Deng H, Xu B. Tetrahedron Lett.
2007;48:8982;
(c) Maruyama K, Kubo Y. J Org Chem. 1981;46:3612.
14. Ueda T, Konishi H, Manabe K, Org Lett. 2013;15:5370.
15. Korsager S, Taaning RH, Lindhardt AT, Skrydstrup T. J Org
Chem. 2013;78:6112.
4.2.24. 4-Chlorophthalimide (3x).
o
1
Yield: 134 mg (75%); white solid; mp: 228.7–229.3 C ; H
NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 8.03–7.56 (m, 3H);
13C NMR (101 MHz, DMSO-d6) δ 168.26, 167.87, 139.08,

7
16. Cacchi S, Fabrizi G, Goggiamani A. J Comb Chem. 2004;6:692.
17. Nasser I, Habib F, Elham ED, Abed R, Khashayar RM, Appl
Organometal Chem. 2015;29:719.
ACCEPTED MANUSCRIPT
18. (a) Yu B, Zhao Y, Zhang HY, Xu JL, Hao LD, Gao X. Liu ZM.
Chem Commun. 2014;50:2330;
(b) Kumar S, Verma S, Jain SL. Tetrahedron Lett. 2015;56:2430;
(c) Qi XX, Li CL, Wu XF. Chem Eur J. 2016;22 ;5835.
19. Amatore C, Jutand A. Acc Chem Res. 2000;33:314.