Synthesis of novel isoindolone-based medium-sized macromolecules and triazole containing heterocyclic compounds

Article abstract of DOI:10.1002/jhet.3704

A series of novel isoindolone-based macromolecules of medium-sized heterocyclic rings, such as 7,8-dihydro-6H-benzo[4,5][1,6,3]dioxazonino[2,3-a]isoindol-14(9aH)-one derivatives (5a-l), were synthesized and its frame work incorporating with a triazole moiety on phenol, ie, 2-(4-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)isoindoline-1,3-dione (9a-f) and also a triazole moiety on carboxylic acid, ie, (1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl 4-(1,3-dioxoisoindolin-2-yl)benzoate derivatives (13a-e) with various substitutions on aryl ring system have synthesized. All the synthesized compounds were characterized and confirmed with IR, ¹H NMR_, ¹³C NMR, and ESI mass spectral analysis.

Full text of DOI:10.1002/jhet.3704

Received: 1 November 2018
DOI: 10.1002/jhet.3704
Revised: 3 July 2019
Accepted: 1 August 2019
A R T I C L E
Synthesis of novel isoindolone‐based medium‐sized
macromolecules and triazole containing heterocyclic
compounds
Lingaiah Boddu | Varakumar Potlapati | N.J.P. Subhashini
Department of Chemistry, University
Abstract
College of Science, Osmania University,
A series of novel isoindolone‐based macromolecules of medium‐sized heterocyclic
Hyderabad, India
rings, such as 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐14
Correspondence
Subhashini N.J.P., Department of
(9aH)‐one derivatives (5a‐l), were synthesized and its frame work incorporating
Chemistry, University College of Science,
Osmania University, Hyderabad, India.
Email: njsubhashini@yahoo.co.in
with a triazole moiety on phenol, ie, 2‐(4‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐
4‐yl)methoxy)phenyl)isoindoline‐1,3‐dione (9a‐f) and also a triazole moiety on
carboxylic acid, ie, (1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐
dioxoisoindolin‐2‐yl)benzoate derivatives (13a‐e) with various substitutions on
aryl ring system have synthesized. All the synthesized compounds were character-
ized and confirmed with IR, 1H NMR, 13C NMR, and ESI mass spectral analysis.
Funding information
University Grants Commission
1 | INTRODUCTION
In our present work, we report the synthesis of macro-
molecules containing medium‐sized rings, such as 7,8‐
Indoline and isoindolines are the heterocyclic regio iso-
mers, fused with benzene and saturated five membered
rings. Isoindoline moiety is an important privilege ring
system, because their derivatives are valuable backbones
for the discovery of various new biologically active mole-
cules including anxiolytic, psycotropic agents, hypnotics,
anticonvulsants, antiepileptics,[1–4] and sedatives.[5,6]
Pazinaclone is a sedative drug, which contains isoindoline
as core moiety. It is used as anxiolytic at low doses and
sedative at high doses. Isoindoline itself not used as a
drug but its analogues, such as modification of functional
groups, elongation or contraction chain or formation of
macromolecules show some remarkable medicinal impor-
tance. Few marketed drugs, which are having isoindolin
framework, are pazinaclone and pagoclone.
dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐
14(9aH)‐one derivatives (5a‐l) containing isoindoline
ring and N‐substituted isoindoline‐1,3‐dione com-
pounds, such as 2‐(4‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)
methoxy)phenyl)isoindoline‐1,3‐dione derivatives (9a‐f)
and
(1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl
4‐(1,3‐
dioxoisoindolin‐2‐yl)benzoate derivatives (13a‐e).
2 | RESULTS AND DISCUSSIONS
The synthesis of 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]
dioxazonino[2,3‐a]isoindol‐14(9aH)‐ones (5a‐l) were from
commodity of chemicals, proceeds in multiple steps, in
which insertion of 5‐substituted 2‐amino phenols (2a‐d)
in pthalic anhydride gave compounds 3a‐d and reduction
of 3a‐d afforded compounds 4a‐d with reported proce-
dures.[7,8] By analyzing the spectral data, we concluded
that out of two carbonyl groups, one carbonyl acts as
ketone, and other carbonyl acts as amide of compounds
1
3a‐d, and they were confirmed by FTIR and H NMR
spectroscopy. The confirmative peak at aliphatic region
J Heterocyclic Chem. 2019;1–9.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

2
BODDU ET AL.
TABLE 2 Physical data of compounds 9a‐f and 13a‐e
as singlet due to benzylic hydrogen and further it was
confirmed by FTIR spectroscopy. Repeated the same syn-
thetic procedure to remaining all the compounds 4a‐d
and finally compounds 4a‐d were cyclized with 1,3‐
dibromo propane and 1,4‐dibromo butane and 1,5‐
dibromo pentane in the presence of sodium hydride
afforded the desired medium‐sized macromolecules 5a‐l
with reported experimental procedure,[9] and complete
physical data were presented in Table 1.
The Synthesis of 2‐(4‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)
methoxy)phenyl)isoindoline‐1,3‐dione derivatives (9a‐f)
were involved in three steps. Here, 4‐amino phenol with
pthalic anhydride in acetic acid at 100°C gave compound
7, and propargylation of compound 7 afforded the corre-
sponding 2‐(4‐(prop‐2‐yn‐1‐yloxy)phenyl)isoindoline‐1,3‐
dione (8) in the presence of potassium carbonate and sub-
sequently treated with various azides (which are gener-
ated from amines, diazotization followed by nucleophilic
substitution) via 1,3‐dipolar cyclo addition (click reaction)
in the presence of 10 mol% of sodium ascorbate and
10 mol% of copper sulphate[10] afforded 2‐(4‐((1‐phenyl‐
Entry
Product
9a
M Pt, °C
170‐172
183‐185
225‐227
260‐262
222‐224
193‐195
174‐176
162‐164
170‐172
164‐166
142‐144
Yielda, %
1
79
81
80
73
70
74
78
62
73
61
76
2
9b
3
9c
4
9d
5
9e
6
9f
7
13a
13b
13c
13d
13e
8
9
10
11
aIsolated yield.
compounds (13a‐e) via 1, 3 dipolar cyclo addition (Click
Reaction) and results were presented in Table 2.
1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)
isoindoline‐1,3‐
dione (9a‐f) derivatives in excellent yields 70% to 81% as
shown in scheme 2 and physical data presented in
Table 2.
3 | CONCLUSION
We have synthesized variety of molecules containing
2‐phenylisoindolin‐1‐one as core moiety. Along with this
core moiety, we have introduced a medium‐sized rings
ranging from 9 to 11 numbered in the final molecules, ie,
7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐
14(9aH)‐one (5a‐l) derivatives and also introduced a 1,2,3‐
triazole ring on the side chain of the phenyl ring of core
moiety with different functional groups. Such as 2‐(4‐((1‐
phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)isoindoline‐
1,3‐dione derivatives (9a‐f) and (1‐phenyl‐1H‐1,2,3‐
triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl) benzoate
derivatives (13a‐e).
Synthesis of (1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl
4‐(1,3‐dioxoisoindolin‐2‐yl) benzoate (13a‐e) were also
involved 3 steps. i.e., insertion of 4‐amino benzoic acid
in pthalic anhydride followed by propargylation gave
prop‐2‐yn‐1‐yl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate (12)
in presence of potassium carbonate and subsequently
treated with various azides and 10 mol% of sodium ascor-
bate and 10 mol% of copper sulphate afforded the final
TABLE 1 Physical data of compounds 5a‐l
Entry
Product
5a
R
n
1
2
3
1
2
3
1
2
3
1
2
3
M Pt, °C
68‐70
Yielda, %
1
H
69
67
61
79
76
72
62
63
59
49
45
46
4 | EXPERIMENTAL
2
5b
H
206‐208
188‐190
70‐72
3
5c
H
All the reagents and solvents are purchased from com-
mercially available sources. Analytical TLC was per-
formed on Merck Silica Gel GF254 plates, visualization
by I2 vapors/UV light. Melting points were recorded in
open capillary tubes on SISCO electrical melting point
apparatus and are uncorrected. IR spectra were obtained
by using Perkin–Elmer spectrophotometer using potas-
4
5d
5e
CH3
CH3
CH3
Cl
5
152‐154
128‐130
96‐98
6
5f
7
5g
8
5h
5i
Cl
174‐176
170‐172
128‐130
150‐152
160‐162
1
sium bromide optics. H and 13C NMR spectra recorded
9
Cl
1
on a Bruker Avance 400 spectrometer (400 MHz for H
10
11
12
5j
NO2
NO2
NO2
NMR and 100 MHz for 13C) in CDCl3/DMSO using TMS
as an internal standard. ESI Mass Spectra recorded on
Quatro LC Micromass (Waters Manchester, UK) mass
Spectrometer.
5k
5l
aIsolated yield.

BODDU ET AL.
3
5a with 69% of yield. Same procedure repeated for
remaining all the compounds.
4.1 | Typical procedure for the synthesis
of 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]
dioxazonino[2,3‐a]isoindol‐14(9aH)‐one
derivatives (5a‐l)
4.2 | Typical procedure for synthesis of 2‐
(4‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)
phenyl)isoindoline‐1,3‐dione derivatives
(9a‐f)
Synthesis of compounds (5a‐l) (Scheme 1) involved in
three steps. In the first step, to a stirred solution of
pthalic anhydride (1, 2 g, 0.013 mol) and 2‐amino phe-
nol (2a, 1.47 g, 0.013 mol) in 20 ml of acetic acid and
stirred at 100°C for 3 hours and poured the reaction
mixture into crushed ice and filtered to afford the
desired compound (3a) with 85% of yield. Second step,
to a stirred solution of compound 3a (0.8 g, 0.003 mol)
in methanol (5 mL) was added sodium borohydride
(0.08 g, 0.002 mol) at 0°C and stirred at RT for 2 hours
to afforded compound 4a with 90% of yield. Final step,
to a stirred solution of compound 4a (0.2 g, 0.008 mol)
in 2 ml of DMF was added sodium hydride (0.384 g,
0.016 mol) at 0°C and stirred for 15 minutes. Then,
added 1,3‐dibromo propane (0.166 g, 0.008 mol) and
stirred it RT for 2 hours to afford the desired compound
Synthesis of compounds (9a‐f) (Scheme 2) was also
involved in three steps. In the first step, dissolved the equi-
molar mixture of pthalic anhydride (1, 2 g, 0.013 mol) and
4‐amino phenol (6, 1.47 g, 0.013 mol) in 20 ml of acetic acid,
stirred at 100°C for 3 hours and poured the reaction
mixture in crushed ice and filtered the solid compound
(7) with 85% of yield. In step 2, to a stirred solution of com-
pound 7 (2 g, 0.008 mol) in 15 ml of DMF was added potas-
sium carbonate (3.46 g, 0.025 mol). Then, added propargyl
bromide (1.18 g, 0.01 mol) and stirred at RT for 2 hours to
afforded the desired compound 2‐(4‐(prop‐2‐yn‐1‐yloxy)
phenyl)isoindoline‐1,3‐dione (8) with 90% of yield. Finally,
SCHEME 1 Conditions: (a) acetic acid,
100°C, 3 hours; (b) sodium borohydride,
methanol, 0°C‐ RT, 2 hours; (c) sodium
hydride, 0°C‐ RT, 2 hours, 1,3‐di bromo
propane/1,4‐dibromo butane/1,5‐dibromo
pentane.
SCHEME 2 Conditions: (a) Acetic acid,
100°C, 3 hours; (b) K2CO3, Propagyl
bromide, DMF, RT, 3 hours; (c) Azides,
10 mol% of sodium ascorbate, 10 mol% of
CuSO4.H2O, DMF: Water (1:1), RT, 10 to
12 hours.

4
BODDU ET AL.
compound 8 (0.2 g, 0.722 mmol) dissolved in 5 ml of DMF:
Water (1:1) was added aromatic azide (0.1 g, 0.8 mmol),
sodium ascorbate (10 mol%), copper sulphate (10 mol%)
and stirred it at room temperature for 10 hours gave com-
pound 9a with yield (79%). Same procedure repeated for
remaining all compounds.
1
Yield 69%, mp 68°C‐70°C. H NMR (CDCl3, 400 MHz), δ
ppm: 3.61‐3.65 (m, 1H), 3.85‐3.90 (m, 1H), 4.55‐4.59 (m,
2H), 5.67‐5.77 (m, 1H), 5.89‐5.99 (m, 1H), 6.51 (s, 1H),
6.99‐7.02 (d, 2H, J = 8.28 Hz), 7.30‐7.39 (m, 2H), 7.54‐7.66
(m, 3H), 7.92 (d, 1H, J = 7.52 Hz). 13C NMR (CDCl3,
100 MHz), δ ppm: 20.5, 64.9, 69.2, 87.6, 113.3, 117.1,
117.2, 123.6, 123.9, 124.6, 129.8, 130.5, 130.6, 132.3, 132.5,
133.9, 141.5, 152.0, 167.2. ESI Mass m/z at 282 [M + H]+.
Elemental analysis calculated for C17H15NO3; C, 72.58; H,
5.37; N, 4.98. Found %: C, 72.67; H, 5.44; N, 5.03.
4.3 | Typical procedure for synthesis of (1‐
phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐
dioxoisoindolin‐2‐yl) benzoate (13a‐e)
Synthesis of compounds (13a‐e) (Scheme 3) was also
involved in three steps. First step, dissolved the equimolar
mixture of pthalic anhydride (1, 2 g, 0.013 mol) and 4‐
amino benzoic acid (10, 1.85 g, 0.013 mol) in 20 mL of
acetic acid, stirred at 100°C for 3 hours and poured into
crushed ice and filtered the solid compound (11) with
83% of yield. Then, to a stirred solution of 4‐(1, 3‐
dioxoisoindolin‐2‐yl) benzoic acid (11, 2 g, 0.0074 mol) in
15 mL of DMF was added K2CO3 (3.1 g, 0.0224 mol), pro-
pargyl bromide (1.06 g, 0.0089 mol), and stirred at RT for
3 hours gave prop‐2‐yn‐1‐yl 4‐(1,3‐dioxoisoindolin‐2‐yl)
benzoate (12) with 87% of yield. Finally, compound 12
(200 mg, 0.655 mmol) was treated with 1‐azido 4‐methyl
benzene (95 mg, 0.721 mmol) in the presence of 10 mol%
of sodium ascorbate and 10 mol% copper sulphate in
5 mL of DMF:Water (1:1) mixture was stirred at RT for
10 hours afforded the desired product (1‐phenyl‐1H‐1,2,3‐
triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl) benzoate
(13) in 78% of yield. Same procedure repeated for remain-
ing all the compounds.
5.2 | 6,7,8,9‐Tetrahydrobenzo[4,5][1,6,3]
dioxazecino[2,3‐a]isoindol‐15(10aH)‐one (5b)
Yield 67%, mp 206°C‐208°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 1.24‐1.29 (m, 1H), 1.37‐1.66 (m, 1H), 1.74‐1.91 (m,
1H), 3.14‐3.18 (m, 1H), 3.67‐3.73 (m, 1H), 4.11‐4.20 (m,
1H), 4.47‐4.51 (m, 1H), 5.04‐5.13 (m, 1H), 6.05 (s, 1H),
7.06‐7.10 (m, 1H), 7.17‐7.25 (m, 2H), 7.37‐7.42 (m, 1H),
7.54‐7.64 (m, 3H), 7.91‐7.94 (m, 1H). ESI Mass m/z at
296 [M + H]+. Elemental analysis calculated for
C18H17NO3; C, 73.20; H, 5.80; N, 4.74. Found %: C,
73.27; H, 5.84; N, 4.79.
5 | SPECTRAL DATA
5.1 | 7,8‐Dihydro‐6H‐benzo[4,5][1,6,3]
dioxazonino[2,3‐a]isoindol‐14(9aH)‐one (5a)
SCHEME 3 Conditions: (a) acetic acid,
100°C, 3 hours; (b) K2CO3, Propagyl
bromide, DMF, RT, 3 h; (c) Azides, 10 mol
% of sodium ascorbate, 10 mol% of CuSO4.
H2O, DMF:Water (1:1), RT, 10 to 12 hours.

BODDU ET AL.
5
131.9, 132.1, 133.1, 140.6, 153.7, 167.4. ESI Mass m/z at
310 [M + H]+. Elemental analysis calculated for
C19H19NO3; C, 73.77; H, 6.19; N, 4.53. Found %: C, 73.86;
H, 6.24; N, 4.59.
5.3 | 7,8,9,10‐Tetrahydro‐6H‐benzo[4,5]
[1,6,3]dioxaazacycloundecino[2,3‐a]
isoindol‐16(11aH)‐one (5c)
5.6 | 3‐Methyl‐7,8,9,10‐tetrahydro‐6H‐
benzo[4,5][1,6,3]dioxaazacycloundecino[2,3‐
a] isoindol‐16 (11aH)‐one (5f)
Yield 61%, mp 188°C‐190°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 1.35‐1.46 (m, 2H), 1.61‐1.68 (m, 3H), 1.82‐1.89 (m,
1H), 2.93‐2.97 (m, 1H), 3.77‐3.88 (m, 2H), 4.24‐4.27 (m,
1H), 6.14 (s, 1H), 6.95‐7.03 (m, 2H), 7.15‐7.17 (d, 1H,
J = 7.52 Hz), 7.33‐7.37 (m, 1H), 7.55‐7.66 (m, 3H), 7.92
(d, 1H, J = 7.52 Hz). ESI Mass m/z at 310 [M + H]+. Ele-
mental analysis calculated for C19H19NO3; C, 73.77; H,
6.19; N, 4.53. Found %: C, 73.84; H, 6.24; N, 4.59.
Yield 72%, mp 128°C‐130°C. 1H NMR (CDCl3,
400 MHz), δ ppm: 1.25‐147 (m, 2H), 1.52‐1.68 (m, 4H),
1.79‐1.86 (m, 1H), 2.28 (s, 3H), 2.93‐2.97 (m, 1H), 3.76‐
3.84 (m, 2H), 4.22‐4.26 (m, 1H), 6.14 (s, 1H), 6.85 (d,
1H, J = 8.28 Hz), 6.97 (d, 1H, J = 1.75 Hz), 7.13‐7.15
(d, 1H, J = 8.28 Hz), 7.54‐7.62 (m, 2H), 7.92 (d, 1H,
J = 7.27 Hz). 13C NMR (CDCl3, 100 MHz), δ ppm:
20.3, 21.5, 26.8, 29.3, 58.6, 69.8, 90.0, 112.8, 123.6,
123.9, 125.5, 129.8, 130.1, 130.3, 132.1, 132.7, 141.5,
155.3, 168.0. ESI Mass m/z at 324 [M + H]+. Elemental
analysis calculated for C20H21NO3; C, 74.28; H, 6.55; N,
4.33. Found %: C, 74.37; H, 6.59; N, 4.39.
5.4 | 3‐Methyl‐7,8‐dihydro‐6H‐benzo[4,5]
[1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐
one (5d)
Yield 79%, mp 70°C‐72°C. 13C NMR (CDCl3, 100 MHz), δ
ppm: 20.5, 64.9, 69.2, 87.6, 113.3, 117.1, 117.2, 123.6,
123.9, 124.6, 129.5, 129.8, 130.5, 130.6, 132.3, 132.5, 133.9,
141.5, 152.0, 167.2. ESI Mass m/z at 296 [M + H]+. Ele-
mental analysis calculated for C18H17NO3; C, 73.20; H,
5.80; N, 4.74. Found %: C, 73.27; H, 5.84; N, 4.79.
5.7 | 3‐Chloro‐7,8‐dihydro‐6H‐benzo[4,5]
[1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐
one (5g)
5.5 | 3‐Methyl‐6,7,8,9‐tetrahydrobenzo[4,5]
[1,6,3]dioxazecino[2,3‐a]isoindol‐15(10aH)‐
one (5e)
1
Yield 62%, mp 96°C‐98°C. H NMR (CDCl3, 400 MHz), δ
ppm: 0.81‐0.86 (m, 1H), 3.57‐3.71 (m, 1H), 5.08 (m, 2H),
5.62‐5.72 (m, 2H), 6.57 (s, 1H), 7.08 (d, 1H, J = 8.78 Hz),
7.23 (d, 1H, J = 8.78 Hz), 7.31 (d, 1H, J = 2.25 Hz), 7.62‐
7.74 (m, 3H), 7.93 (d, 1H, J = 7.52 Hz). 13C NMR
(CDCl3, 100 MHz), δ ppm: 29.7, 64.6, 87.9, 117.9,
121.7, 123.7, 124.2, 125.8, 128.4, 130.7, 131.2, 132.9,
133.4, 141.4, 150.0, 168.0. ESI Mass m/z at 316
Yield 76%, mp 152°C‐154°C. 1H NMR (CDCl3, 400 MHz), δ
ppm: 1.33‐1.42 (m, 1H), 1.45‐1.53 (m, 1H), 1.74‐1.91 (m,
2H), 2.31 (s, 3H), 3.12‐3.16 (m, 1H), 3.67‐3.73 (m, 1H),
4.14 (t, 1H, J = 11.54 Hz), 4.43‐4.47 (m, 1H), 6.05 (s, 1H),
7.04 (d, 1H, J = 1.75 Hz), 7.06‐7.09 (d, 1H, J = 8.53 Hz),
7.18 (m, 1H), 7.53‐7.63 (m, 3H), 7.92 (d, 1H, J = 7.20 Hz).
13C NMR (CDCl3, 100 MHz), δ ppm: 20.5, 23.1, 28.6, 60.8,
71.7, 89.2, 117.0, 123.7, 124.0, 127.7, 129.8, 130.5, 130.6,
[M
+
H]+. Elemental analysis calculated for
C17H14NClO3; C, 64.67; H, 4.47; N, 4.44. Found %: C,
64.74; H, 4.52; N, 4.49.

6
BODDU ET AL.
J
=
9.03 Hz), 7.65‐7.78 (m, 3H), 7.96 (d, 1H,
5.8 | 3‐Chloro‐6,7,8,9‐tetrahydrobenzo[4,5]
[1,6,3]dioxazecino[2,3‐a]isoindol‐15(10aH)‐
one (5h)
J = 7.27 Hz), 8.16‐8.18 (d, 1H, J = 9.03 Hz), 8.31 (d, 1H,
J = 2.51 Hz). ESI Mass m/z at 328 [M + H]+. Elemental
analysis calculated for C17H14N2O5; C, 62.57; H, 4.32; N,
8.59. Found %: C, 62.66; H, 4.37; N, 8.67.
5.11 | 3‐Nitro‐6,7,8,9‐tetrahydrobenzo[4,5]
[1,6,3]dioxazecino[2,3‐a]isoindol‐15(10aH)‐
one (5k)
Yield 63%, mp 174°C‐176°C. 1H NMR (CDCl3,
400 MHz), δ ppm: 1.39‐1.51 (m, 2H), 1.75‐1.84 (m, 2H),
3.14‐3.18 (m, 1H), 3.62‐3.68 (m, 1H), 4.15‐4.21 (m, 1H),
4.41‐4.45 (m, 1H), 6.05 (m, 1H), 7.11 (d, 1H,
J
J
=
=
8.78 Hz), 7.25 (m, 1H), 7.35‐7.38 (d, 1H,
8.78 Hz), 7.55‐7.66 (m, 3H), 7.82 (d, 1H,
J = 8.53 Hz). ESI Mass m/z at 330 [M + H]+. Elemental
analysis calculated for C18H16ClNO3; C, 65.56; H, 4.89;
N, 4.25. Found %: C, 65.64; H, 4.93; N, 4.29.
Yield 45%, mp 150°C‐152°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 1.77‐1.86 (m, 1H), 2.11‐2.16 (m, 1H), 3.07‐3.25 (m,
1H), 3.59‐3.64 (m, 1H), 4.30‐4.38 (m, 1H), 4.51‐4.55 (m,
1H), 4.87‐4.94 (m, 1H), 5.45‐5.52 (m,1H), 6.07 (s, 1H),
6.68 (d, 1H, J = 9.53 Hz), 7.20‐7.24 (m, 1H), 7.58‐7.69
(m, 3H), 7.93 (m, 1H), 8.22 (d, 1H, J = 2.76 Hz). ESI Mass
m/z at 342 [M + H]+. Elemental analysis calculated for
C18H16N2O5; C, 63.52; H, 4.74; N, 8.23. Found %: C,
63.59; H, 4.78; N, 8.28.
5.9 | 3‐Chloro‐7,8,9,10‐tetrahydro‐6H‐benzo
[4,5][1,6,3]dioxaazacycloundecino[2,3‐a]
isoindol‐16(11aH)‐one (5i)
5.12 | 3‐Nitro‐7,8,9,10‐tetrahydro‐6H‐benzo
[4,5][1,6,3]dioxaazacycloundecino[2,3‐a]
isoindol‐16(11aH)‐one (5l)
Yield 59%, mp 170°C‐172°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 0.79‐0.88 (m, 1H), 1.28‐1.42 (m, 3H), 1.62 (m, 1H),
1.82‐1.88 (m, 1H), 2.94–2.98 (m, 1H), 3.72‐3.84 (m, 2H),
4.23‐4.27 (m, 1H), 6.14 (s, 1H), 6.88 (d, 1H, J = 8.78 Hz),
7.17 (d, 1H, J = 2.76 Hz), 7.30‐7.33 (d, 1H, J = 8.78 Hz),
7.55‐7.73 (m, 3H), 7.92 (d, 1H, J = 8.53 Hz). ESI Mass
m/z at 344 [M + H]+. Elemental analysis calculated for
C19H18ClNO3; C, 66.38; H, 5.28; N, 4.07. Found %: C,
66.75; H, 5.32; N, 4.12.
Yield 46%, mp 160°C‐162°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 1.37‐1.58 (m, 2H), 1.62‐1.70 (m, 2H), 1.84‐1.90 (m,
1H), 3.05‐3.15 (m, 2H), 3.23‐3.27 (m, 1H), 4.80‐4.86 (m,
1H), 5.54‐5.64 (m, 1H), 6.18 (s, 1H), 6.68 (d, 1H,
J = 7.78 Hz), 7.19‐7.23 (m, 1H), 7.66‐7.77 (m, 2H), 7.95‐
7.97 (m, 1H), 8.15‐8.18 (m, 1H), 8.30 (d, 1H,
J = 2.76 Hz). 13C NMR (CDCl3, 100 MHz), δ ppm: 24.5,
28.3, 29.6, 32.1, 33.3, 62.7, 62.8, 88.1, 88.2, 115.0, 120.4,
120.5, 120.7, 120.8, 123.7, 123.9, 124.4, 124.5, 125.0,
130.7, 130.8, 130.9, 133.9, 137.3, 141.4, 157.1, 16.7. ESI
Mass m/z at 356 [M + H]+. Elemental analysis calculated
for C19H18N2O5; C, 64.40; H, 5.12; N, 7.91. Found %: C,
64.51; H, 5.17; N, 7.98.
5.10 | 3‐Nitro‐7,8‐dihydro‐6H‐benzo[4,5]
[1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐
one (5j)
Yield 49%, mp 128°C‐130°C. 1H NMR (CDCl3, 400 MHz),
δ ppm: 3.63‐3.72 (m, 2H), 5.07‐5.10 (m, 2H), 5.12‐5.14 (m,
1H), 5.61‐5.71 (m, 1H), 6.70 (s, 1H), 7.21 (d, 1H,

BODDU ET AL.
7
2H), 7.03 (d, 2H, J = 9.03 Hz), 7.15 (d, 2H, J = 9.03 Hz),
7.36 (d, 2H, J = 9.03 Hz), 7.65 (d, 2H, J = 9.03 Hz), 7.79
(q, 2H, J = 3.01 Hz), 7.95 (q, 2H, J = 3.01 Hz), 7.99 (s,
1H). 13C NMR (100 MHz, CDCl3), δ ppm: 55.6, 62.3,
114.8, 115.3, 121.1, 1222.3, 123.7, 124.9, 128.0, 130.4,
131.8, 134.3, 144.4, 157.8, 159.9, 167.5. ESI Mass m/z at
427 [M + H]+. Elemental analysis calculated for
C24H18N4O4; C, 67.60; H, 4.25; N, 13.14. Found %: C,
67.71; H, 4.29; N, 13.21.
5.13 | 2‐(4‐((1‐Phenyl‐1H‐1,2,3‐triazol‐4‐yl)
methoxy)phenyl)isoindoline‐1,3‐dione (9b)
1
Yield 81%, mp 183°C‐185°C. IR (cm−1) 1694, 3158. H
NMR (400 MHz, CDCl3), δ ppm: 5.36 (s, 2H), 7.15 (d,
2H, J = 9.03 Hz), 7.36 (d, 2H, J = 9.03 Hz), 7.46 (m,
1H), 7.54 (m, 2H), 7.49‐7.81 (m, 4H), 7.95 (m, 2H), 8.08
(s, 1H). 13C NMR (100 MHz, CDCl3), δ ppm: 62.3, 115.3,
120.7, 121.0, 123.7, 124.9, 128.9, 129.8, 131.7, 134.3,
136.9, 144.7, 157.7, 167.5. ESI Mass m/z at 397
5.16 | 2‐(4‐((1‐(2‐chlorophenyl)‐1H‐1,2,3‐
triazol‐4‐yl)methoxy)phenyl)isoindoline‐
1,3‐dione (9d)
[M
+
H]+. Elemental analysis calculated for
C23H16N4O3; C, 69.69; H, 4.07; N, 14.13. Found %: C,
69.76; H, 4.14; N, 14.19.
5.14 | 2‐(4‐((1‐(2‐Methoxyphenyl)‐1H‐1,2,3‐
triazol‐4‐yl)methoxy)phenyl)isoindoline‐
1,3‐dione (9b)
1
Yield 73%, mp 260°C‐262°C. IR (cm−1) 1701, 2933. H
NMR (400 MHz, CDCl3), δ ppm: 5.35 (s, 2H), 7.14 (d,
2H, J = 9.03 Hz), 7.36 (d, 2H, J = 9.03 Hz), 7.42‐7.50
(m, 2H), 7.65‐7.67 (m, 1H), 7.78‐7.80 (q, 2H,
J = 3.01 Hz), 7.82 (m, 1H), 7.95 (q, 2H, J = 3.01 Hz),
8.07 (s, 1H). ESI Mass m/z at 431 [M + H]+. Elemental
analysis calculated for C23H15ClN4O3; C, 64.12; H, 3.51;
N, 13.00. Found %: C, 64.18; H, 3.58; N, 13.06.
1
Yield 79%, mp 170°C‐172°C. IR (cm−1): 1678, 3000. H
NMR (400 MHz, CDCl3), δ ppm: 3.91 (s, 3H), 5.59 (s,
2H), 7.10 (m, 2H), 7.43 (m, 1H), 7.58 (d, 2H,
J = 8.78 Hz), 7.78‐7.82 (m, 3H), 7.96‐8.01 (m, 2H) 8.21
5.17 | 2‐(4‐((1‐(4‐Chlorophenyl)‐1H‐1,2,3‐
triazole‐1‐yl)methoxy)phenyl)isoindoline‐
1,3‐dione (9e)
13
(d, 2H, J = 8.78 Hz), 8.26 (s, 1H). C NMR (100 MHz,
CDCl3), δ ppm: 56.0, 62.3, 112.2, 115.4, 121.2, 123.7,
124.8, 125.1, 125.5, 126.2, 128.0, 130.2, 131.8, 134.3,
143.2, 151.1, 157.9, 167.9. ESI Mass m/z at 427
[M
+
H]+. Elemental analysis calculated for
C24H18N4O4; C, 67.60; H, 4.25; N, 13.14. Found %: C,
67.69; H, 4.31; N, 13.19.
5.15 | 2‐(4‐((1‐(4‐Methoxyphenyl)‐1H‐1,2,3‐
triazol‐4‐yl)methoxy)phenyl)isoindoline‐
1,3‐dione (9c)
1
Yield 70%, mp 260°C‐262°C. IR (cm−1) 1693, 2956. H
NMR (400 MHz, CDCl3), δ ppm: 5.35 (s, 2H), 7.14 (d,
2H, J = 9.03 Hz), 7.36 (d, 2H, J = 9.03 Hz), 7.52 (d, 2H,
J = 8.78 Hz), 7.71(d, 2H, J = 9.03 Hz), 7.79 (q, 2H,
J = 3.01 Hz), 7.93 (q, 2H, J = 3.01 Hz), 8.05 (s, 1H). 13C
NMR (100 MHz, CDCl3), δ ppm: 62.2, 115.3, 120.9,
121.8, 123.7, 124.9, 128.1, 130.0, 131.7, 134.4, 134.7,
135.4, 144.9, 157.7, 167.5. ESI Mass m/z at 431
[M
+
H]+. Elemental analysis calculated for
C23H15ClN4O3; C, 64.12; H, 3.51; N, 13.00. Found %: C,
64.21; H, 3.56; N, 13.12.
Yield 80% mp 225°C‐227°C. IR (cm−1) 1678, 3064. 1H
NMR (400 MHz, CDCl3), δ ppm: 3.87 (s, 3H), 5.35 (s,

8
BODDU ET AL.
C25H18N4O5; C, 66.08; H, 3.99; N, 12.33. Found %: C,
66.19; H, 4.04; N, 12.37.
5.18 | (1‐(2‐Methoxyphenyl)‐1H‐1,2,3‐
triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐
yl)benzoate (13a)
5.21 | (1‐(4‐Chlorophenyl)‐1H‐1,2,3‐triazol‐
4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)
benzoate (13d)
Yield 78%, mp. 174°C‐176°C. 1H NMR (400 MHz, CDCl3),
δ, ppm: 3.90 (s, 3H), 5.59 (s, 2H), 7.08‐7.13 (m, 2H), 7.41‐
7.45 (m, 1H), 7.59 (d, 2H, J = 8.78 Hz), 7.78‐7.82 (m, 3H),
7.96‐7.98 (m, 2H), 8.21 (d, 2H, J = 8.78 Hz), 8.26 (s, 1H).
ESI Mass m/z at 455 [M + H]+. Elemental analysis calcu-
lated for C25H18N4O5; C, 66.08; H, 3.99; N, 12.33. Found
%: C, 66.12; H, 4.08; N, 12.42.
Yield 61%, mp 164°C‐166°C. 1H NMR (400 MHz, CDCl3),
δ ppm: 5.58 (s, 3H), 7.50‐7.52 (d, 2H, J = 9.03 Hz), 7.59‐
7.61 (d, 2H, J = 8.28 Hz), 7.70‐7.72 (d, 2H, J = 8.28 Hz),
7.81‐7.83 (m, 2H), 7.96‐7.98 (m, 2H), 8.12 (s, 1H), 8.19‐
8.21 (d, 2H, J = 8.78 Hz). 13C NMR (100 MHz, CDCl3),
δ ppm: 56.3, 58.2, 123.9, 125.9, 126.1, 127.8, 127.9, 128.6,
128.8, 130.6, 130.8, 130.9, 131.5, 134.7, 136.1, 142.6,
165.6, 166.7. ESI Mass m/z at 459 [M + H]+. Elemental
analysis calculated for C24H15ClN4O4; C, 62.82; H, 3.29;
N, 12.21. Found %: C, 62.89; H, 3.35; N, 12.29.
5.19 | (1‐(2‐Chlorophenyl)‐1H‐1,2,3‐triazol‐
4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)
benzoate (13b)
5.22 | (1‐(p‐Tolyl)‐1H‐1,2,3‐triazol‐4‐yl)
methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate
(13e)
Yield 62%, mp 162°C‐164°C. 1H NMR (400 MHz, CDCl3),
δ ppm: 5.61 (s, 2H), 7.33‐7.50 (m, 2H), 7.58‐7.65 (m, 4H),
7.80‐7.84 (m, 2H), 7.96‐7.98 (m, 2H), 8.15 (s, 1H), 8.21 (d,
2H, J = 8.78 Hz). 13C NMR (100 MHz, CDCl3), δ ppm: ESI
Mass m/z at 459 [M + H]+. Elemental analysis calculated
for C24H15ClN4O4; C, 62.82; H, 3.29; N, 12.29.
Yield 76%, mp 142°C‐144°C. 1H NMR (400 MHz, CDCl3),
δ ppm: 2.68 (s, 3H), 5.60 (s, 2H), 7.60‐7.68 (m, 3H), 7.81‐
7.83 (m, 2H), 7.96‐8.06 (m, 4H), 8.20‐8.23 (m, 3H), 8.31
(s, 1H). 13C NMR (100 MHz, CDCl3), δ ppm: 56.0, 58.3,
112.2, 121.2, 123.9, 125.5, 125.9, 126.1, 128.9, 130.2,
131.5, 134.7, 136.0, 142.1, 151.1, 165.7, 166.7. ESI Mass
m/z at 439 [M + H]+. Elemental analysis calculated for
C25H18N4O4; C, 68.49; H, 4.14; N, 12.78. Found %: C,
68.53; H, 4.16; N, 12.83.
5.20 | (1‐(4‐Methoxyphenyl)‐1H‐1,2,3‐
triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐
yl)benzoate (13c)
Yield 73%, mp 170°C‐172°C. 1H NMR (400 MHz, CDCl3),
δ ppm: 3.87 (s, 3H), 5.58 (s, 2H), 7.02 (d, 2H, J = 8.03 Hz),
7.59‐7.69 (m, 4H), 7.82 (m, 2H), 7.86 (m, 2H), 8.06 (s, 2H),
8.20 (d, 2H, J = 8.28 Hz). 13C NMR (100 MHz, CDCl3), δ
ppm: 55.6, 58.3, 114.8, 122.3, 123.9, 125.9, 128.8, 130.6,
131.5, 134.7, 136.1, 159.9, 165.7, 166.7. ESI Mass m/z at
455 [M + H]+. Elemental analysis calculated for
ACKNOWLEDGMENTS
Authors are grateful to the head, Department of Chemis-
try, Osmania University, Hyderabad for providing labora-
tory facilities and also thankful to CFRD for analytical
facilities, OU. NJPS and LB are is thankful to the UGC‐
New Delhi for providing Senior Research fellowship

BODDU ET AL.
9
[7] I. Clarina, C. L. Manley‐King, J. J. Bergh, J. P. Petzer, Bioorg
Med Chem 2011, 19, 4829.
and OU‐DST‐PURSE‐II/60/2018‐2019 (funding agency),
DRS‐II and SAP program for financial assistance.
[8] T. Kametani, S. Hibino, S. Takano, J ChemSoc D 1971, 16, 925.
[9] V. S. Ranade, G. Consiglio, R. Prins, J Organomet Chem 2000,
65(4), 1132.
ORCID
[10] N. J. P. Subhashini, L. Boddu, J. Amanaganti, Shivaraj, Rus Jou
Gen Chem 2014, 84(7), 1442.
N.J.P. Subhashini https://orcid.org/0000-0003-3852-6043
REFERENCES AND NOTES
SUPPORTING INFORMATION
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