Synthesis and spectral characterization of benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14h)-one derivatives

Article abstract of DOI:10.3390/molecules21080967

A simple synthetic route affording 27%-85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluenesulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra.

Full text of DOI:10.3390/molecules21080967

molecules
Article
Synthesis and Spectral Characterization of
Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-
(14H)-one Derivatives
Jatinder P. Bassin *, Bhavani Anagani, Christopher Benham, Madhu Goyal, Maryam Hashemian
and Ute Gerhard *
School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK;
bhavani.anagani@gmail.com (B.A.); c.d.benham@herts.ac.uk (C.B.); m.goyal@herts.ac.uk (M.G.);
u.gerhard@herts.ac.uk (M.H.)
* Correspondence: j.p.bassin@herts.ac.uk (J.P.B.); u.gerhard@herts.ac.uk (U.G.); Tel.: +44-1707-285097 (J.P.B.);
+44-1707-284511 (U.G.)
Academic Editor: Philippe Belmont
Received: 28 June 2016; Accepted: 20 July 2016; Published: 23 July 2016
Abstract: A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-
a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-
1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-
sulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a
variety of one and two-dimensional NMR experiments. The distinction between the two potential
isomers of the final products was made on the basis of heteronuclear multiple bond connectivity
(HMBC) NMR spectra.
Keywords: diazocine; isoindole; isobenzofuran-1(3H)-ones; 2D-NMR
1. Introduction
In recent years the synthesis and chemistry of medium ring heterocycles has attracted considerable
attention because they are often present in biologically active natural products and because of their
broad pharmacological profile [1]. Nitrogen-containing eight-membered heterocycles such as azocines
and diazocines are known to exhibit a number of important biological properties [
2–5
]. The general
strategies towards the synthesis of eight-membered heterocycles remain an active area of research
and the most common synthetic approach to construct diazocine rings involves the conventional
condensation reaction of 2-aminobenzophenones. However, this method is time-consuming, and the
yield varies with different substrates. Furthermore, the syntheses of 2-aminobenzophenones can be
fairly complicated and expensive [
limited [7].
6]. As a result, synthetic strategies for diazocines preparation are
The isoindole ring system plays a key role in many pharmaceutical agents owing to their
broad range of biological activities [ 14]. Isoindolinones are the core of many natural products
and biologically active compounds such as the benzazepine alkaloids lennoxamine ( ) and
jamtine ( ) (Figure 1). The literature shows that the occurrence of medium-sized rings with two
8
–
1
2
nitrogen atoms in bio-active compounds increases the pharmaceutical strength and activities of the
compounds. The [1,5]benzodiazocines are known as homologs of 1,4-benzodiazepines and inhibitors of
17β-hydroxysteroid dehydrogenase type 3. The 17β-hydroxysteroid dehydrogenases play key roles in
the formation of active intracellular sex steroids [15]. Impairment of this testosterone-converting
enzyme has been shown to be responsible for male pseudohermaphroditism [16], moreover,
[1,5]benzodiazocine derivatives showed low to moderate ability to inhibit the 17
β-hydroxysteroid
dehydrogenase type 3 enzyme which can be used in the treatment of hormone-dependent cancer.
Molecules 2016, 21, 967; doi:10.3390/molecules21080967
www.mdpi.com/journal/molecules

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Interest and research in the preparation of compounds containing eight-membered rings has increased
considerably in recent years. However, the formation of these ring systems is a challenge for synthetic
chemistry researchers. Due to unfavourable entropic and enthalpic effects, the ring closure to form
eight-membered rings by intramolecular cyclisation reactions is often difficult in comparison to smaller
sized rings. As a result, the usual synthetic strategies for the preparation of other ring systems cannot
always be applied to eight-membered rings. Several conventional approaches such as intramolecular
cyclization, intermolecular cyclization, palladium-catalyzed, Ugi Four-Center Three-Component
coupling reaction (U-4C-3CR), use of microwave radiation, Morita–Baylis–Hillman reaction and
intramolecular Friedel–Crafts strategies have been reported in the literature [17–27]. Despite the large
number of literature reports on the conventional synthesis of diazocine skeletons, these conventional
methods suffer from some drawbacks such as long reaction times, harsh reaction conditions,
low-product yields, high cost, toxic by-products and use of toxic catalysts. Therefore, there is a need to
introduce new and more efficient methods in order to develop the synthesis of medium-sized rings
in the pharmaceutical industry. Interesting biological activities are shown by compounds containing
five or six membered heterocyclic rings fused to diazocines [28–34]. Compound 3, a potent and orally
bioavailable Smac mimetic, inhibits cell growth and induces apoptosis in cancer cells and has been
shown to be a potent antagonist of inhibitor of apoptosis proteins (IAPs). It is in phase 1 clinical trials
for the treatment of human cancer [35–37].
Figure 1. Biologically active isoindoles and fused diazocines 1–3.
2. Results and Discussion
Our interest in the synthesis of heterocyclic rings fused to medium sized rings led us to envisage
a straightforward synthetic approach to the benzo[6,7][1,5]diazocine[2,1-a]isoindol-12-(14H)-one ring
system [38,39]. A number of 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones 4a–m were synthesized
following the reported literature procedures [40–51] (Table 1).
Table 1. Formation of isobenzofuran-1(3H)-ones 4a–4m.
Melting Points (˝C)
Literature [Reference]
Compound
Yield (%)
R
Found
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
4-FC6H4
74
65
76
79
45
75
67
81
62
56
63
68
54
142–44
139–41
136–37
95–96
144–45
127–29
107–108
135–36
116–117
108–109
102–103
110–111
135–137
146–147 [42]
146 [48]
142–144 [51]
91–92 [47]
147–149 [42]
124–127 [52]
—
130–133 [52]
114 [47]
104–105 [47]
—
2-FC6H4
4j
4k
4l
3-CH3-C6H4
2-CH3C6H4
3-CH3OC6H4
2-Thienyl
134–135 [42]
138 [49]
4m

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All isobenzofuran-1(3H)-ones synthesized in this work, except compounds 4g and 4k
,
are known and their melting points and spectral characterization showed good agreement
with the literature values. Compounds 4g and 4k were fully characterized by spectral data.
Previous work had reported the reaction of hydrazine with a number of 3-(2-oxo-2-phenylethyl)
isobenzofuran-1(3H)-ones to yield pyrazolo[5,1-a]isoindol-8-ones [52]. More recently the reaction of
o-phenylenediamine with 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones has been reported to
yield 7,7a-dihydro-12H-isoindolo[2,1-a][1,5]benzodiazepin-12-one derivatives [53]. We anticipated
that the reaction of 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones
could yield either compound 5 or 6 (Scheme 1).
4 with 2-aminobenzylamine
Scheme 1. Synthesis of benzo[6,7][1,5]diazocine[2,1-a]isoindol-12(14H)-one 5a
–5m. Reagents and
conditions: (a) RCOCH3, NaOH, RT. (b) 2-aminobenzylamine, p-TsOH, toluene, reflux 24 h.
Benzo[6,7][1,5]diazocine[2,1-a]isoindol-12(14H)-one 5a
sequence. In the first step 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones 4a
moderate to good yields following a known reported literature method [47]. Reaction of 4a
2-aminobenzylamine afforded 5a 5m in moderate to good yields (27%–85%) (Table 2). We envisaged
–
5m were prepared in a simple two-step
4m were prepared in
4m with
–
–
–
that either regioisomer 5 or 6 could form, depending upon the mechanistic pathway followed.
Table 2. Formation of benzo[6,7][1,5]diazocine[2,1-a]isoindol-12(14H)-ones 5a–5m.
R
Compound
Yield (%)
C6H5
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-BrC6H4
3-BrC6H4
2-BrC6H4
4-FC6H4
5a
5b
5c
5d
5e
5f
5g
5h
5i
74
75
73
73
85
72
27
72
55
68
40
62
32
3-FC6H4
3-CH3C6H4
2-CH3C6H4
3-CH3OC6H4
2-Thienyl
5j
5k
5l
5m

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To investigate the regiochemistry of the reaction (Scheme 1), a full characterisation by NMR
spectroscopy and assignment of compounds 5a 5b 5f and 5h were undertaken (Tables 3 and 4).
,
,
The numbering scheme is presented in Figure 2 and assignments of the proton and carbon spectra are
summarized in Tables 3 and 4, respectively.
Figure 2. Numbering scheme of 5a for the purpose of NMR assignments.
Table 3. Proton NMR assignments of compounds 5a, 5b, 5f and 5h (chemical shift, ppm) [a]
.
Proton [b]
Compound 5a
Compound 5b
Compound 5f
Compound 5h
7<‘>
7<“>
2.30
3.66
2.30
3.59
2.30
3.58
2.31
3.60
14<‘>
3.71
3.66
3.67
3.68
7a
4.55
4.52
4.53
4.53
14<“>
5.31
5.31
5.32
5.31
4
2
7.03
7.13
7.02
7.14
7.02
7.15
7.02
7.14
3
10
9
7.30
7.47
7.30
7.49
7.31
7.23–7.33
7.48
7.55–7.62
7.55–7.62
—
7.23–7.33
7.23–7.33
7.76
7.43–7.51
7.55–7.63
7.55–7.63
7.72
—
7.43–7.51
7.76
7.52–7.65
7.52–7.65
7.52–7.65
7.52–7.65
7.52–7.65
7.76
7.53–7.63
7.53–7.63
—
7.53–7.63
7.53–7.63
7.76
8
4’
3’
5’
1
11
2’
6’
7.83
8.18
8.18
7.83
8.13
8.13
7.83
8.36
8.07
7.83
8.19
8.19
[a]
All chemical shifts quoted were referenced to the residual solvent signal of CDCl3; [b] <‘> and <“> represent
germinal protons with different chemical shifts.
The assignments were based on a combination of proton and carbon homo- and heteronuclear
2D NMR experiments. There is potential to form two isomers (compounds 5 and 6, Scheme 1) in the
final step of the reaction and the chemical shift assignments were made to establish the structure of the
products formed. Many of the long range proton-carbon correlations observed in the heteronuclear
multiple bond connectivity spectra (HMBC: see supplementary material) fit either of the two isomers
(Figure 3).

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Table 4. Carbon NMR assignments of compounds 5a, 5b, 5f and 5h (chemical shifts, ppm) [a]
.
Carbon
Compound 5a
Compound 5b
Compound 5f
Compound 5h
36.24
42.01
56.33
7
14
7a
4
36.28
42.02
56.11
36.19
42.00
56.30
36.30
41.99
56.22
121.21
121.91
123.99
125.09
126.16
127.74
127.80
128.80
128.84
129.00
129.13
131.42
131.64
131.78
132.62
137.18
143.90
148.78
165.68
167.16
121.14
121.84
124.07
125.28
126.08
129.04
129.08
128.84
128.94
129.40
129.34
137.76
131.68
131.85
132.59
135.58
143.69
148.50
164.43
167.12
121.11
121.89
124.06
125.40
125.95
131.02
126.09
128.87
128.96
123.57
130.54
134.29
131.69
131.88
132.57
139.20
143.66
148.35
164.23
167.12
121.19
121.84
124.06
125.19
126.14
129.92
129.86
128.83
128.92
116.09
116.23
164.80
131.66
131.82
132.60
133.38
143.75
148.58
164.35
167.13
8
11
2
14a
2’
6’
3
10
3’
5’
4’
1
3JC-F 8.7 Hz
3JC-F 8.7 Hz
2JC-F 21.7 Hz
2JC-F 21.7 Hz
1JC-F 252.9 Hz
9
11a
1’
7b
4a
6
12
[a]
All chemical shifts quoted were referenced to the carbon signal of CDCl3.
Figure 3. Potential reaction products formed.
However, correlations from the methylene group protons H14 to the carbonyl group C12 are
indicative of structure . The assignment of C12 is confirmed by the long range proton-carbon
5
correlation between H11 and C12.
Protons H7 and H14 from the methylene groups correlate with carbon 7a. Typically, correlations
spanning two to three bonds are observed in the HMBC experiment and the methylene group protons
next to the nitrogen in structure
highly unlikely to be observed if structure
support the conclusion that isomer was formed in this reaction. Other derivatives, where no 2D-NMR
6
are too far removed from carbon atoms C7a and C12 and, therefore,
6
were formed in the reaction. The NMR analyses fully
5
data were acquired follow the proton and carbon chemical shifts patterns of the fully characterized
derivatives 5a, 5b, 5f and 5h and, therefore, the same regiochemistry was inferred.
3. Materials and Methods
3.1. General Information
All chemicals were purchased form Sigma Aldrich (Dorset, UK) or Merck (Nottingham, UK)
and were used without further purification. Melting points were determined using a Gallenkamp
melting point apparatus (Thermo Fisher Scientific, Paisley, UK) and are uncorrected. NMR spectra

Molecules 2016, 21, 967
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(
(
at 600 MHz for protons and 151 MHz for 13C) were recorded on a ECA 600 MHz NMR instrument
JEOL Co Ltd., Tokyo, Japan) equipped with a 5 mm gradient broadband probe. Tetramethylsilane was
used as internal standard and solvents as indicated. Chemical shifts were measured in ppm (δ)
relative to TMS (0.00 ppm) or the residual solvent peaks. Coupling constants (J) are reported
in Hertz (Hz). LC-MS spectra were obtained with a spectrometer equipped with an ESI source
(Varian: 210 LC pumps ˆ 2, 1200 L Quadrapole MS/MS, 410 autosampler) (Varian (now Agilent),
Oxford, UK) using a gradient solvent system of A: Water/0.1% formic acid and B: acetonitrile/0.1%
formic acid. Infrared spectra were recorded with a Varian 800 FT-IR spectrophotometer (Varian).
3.2. General Procedure for the Synthesis of 3-(2-Oxo-2-phenylethyl)isobenzofuran-1(3H)-ones 4a–4m
To a stirred solution of 2-carboxybenzaldehyde (15.0 g; 0.1 mol) dissolved in ethanol (50 mL)
in a 1 L three-necked round bottom flask was added the relevant acetophenone (0.1 mol). The flask
was immersed in a bath of crushed ice. Sodium hydroxide (75 mL, 1.75 M) was added dropwise
and the mixture was stirred mechanically for 4 h. The resulting mixture was neutralized with
dilute hydrochloric acid. Diethyl ether (approximately 50 mL) was added to precipitate the product.
The crude product was filtered, washed with a small volume of distilled water and recrystallized from
dichloromethane and ethanol.
˝
3-(2-Oxo-2-phenylethyl)isobenzofuran-1(3H)-one (4a). White powder, yield 74%, m.p. 142–144 C
(lit. 146–147 C [42]). IR (KBr) cm´1 1685 (C=O), 1742 (C=O). H-NMR (CDCl3):
d, J = 7.6 Hz, 1H), 7.68 (t, J = 7.6 Hz, 1H), 7.49–7.62 (m, 4H), 7.44 (d, J = 1.4 Hz, 1H), 7.29–7.40
(m, 1H), 6.10 (t, J = 6.5 Hz, 1H), 3.64 (dd, J = 17.2, 6.9 Hz, 1H), 3.46 (dd, J = 17.9, 6.2 Hz, 1H). 13C-NMR
(CDCl3) 195.74 (C=O), 169.87 (C=O), 149.47, 135.91, 134.04, 133.60, 129.17, 128.56, 127.91, 125.61,
125.42, 122.53, 76.80, 43.38. MS (ESI, m/z) 251.05 [M]+.
δ (ppm) 7.91
˝
1
(
δ
˝
3-(2-(4-Chlorophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4b). White powder, yield 65%, m.p. 139–141 C
(lit. 146 C [48]). IR (KBr) cm 1691 (C=O), 1742 (C=O). 1H-NMR (CDCl3):
7.66 (t, J = 7.3 Hz, 1H), 7.54 (t, J = 6.9 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 6.15 (t, J = 6.9 Hz, 1H), 3.72
dd, J = 17.4, 5.5 Hz, 1H), 3.36 (dd, J = 17.4, 6.4 Hz, 1H). 13C-NMR (CDCl3)
194.80 (C=O), 169.99 (C=O),
δ (ppm) 7.82–8.01 (m, 3H),
˝
´1
(
δ
149.52, 140.46, 134.48, 134.31, 129.57, 129.53, 129.19, 125.89, 125.82, 122.70, 76.79, 43.66. MS (ESI m/z)
285.0 [M]+.
˝
3-(2-(3-Chlorophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4c). White powder, yield 76%, m.p. 126–127 C
(lit. 142–144 ˝C [51]). IR (KBr) cm´1 1691 (C=O), 1747 (C=O). 1H-NMR (CDCl3):
(ppm) 7.84–7.97
(m, 1H), 7.59–7.75 (m, 4H), 7.51–7.59 (m, 2H), 7.46 (td, J = 8.0, 5.0 Hz, 1H), 7.27–7.35 (m, 1H), 6.15
t, J = 6.4 Hz, 1H), 3.73 (dd, J = 17.4, 6.0 Hz, 1H), 3.33–3.45 (m, 1H). 13C-NMR (CDCl3)
194.76 (C=O),
δ
(
δ
169.95 (C=O), 149.44, 137.63, 135.25, 134.31, 133.78, 130.18, 129.54, 128.23, 126.25, 125.83, 122.66, 76.79,
43.79. MS (ESI m/z) 285.0 [M]+.
˝
3-(2-(2-Chlorophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4d). White powder, yield 79%, m.p. 95–96 C
(lit. 91–92 C [47]). IR (KBr) cm´1 1678 (C=O), 1735 (C=O). H-NMR (CDCl3):
(m, 1H), 7.62–7.74 (m, 1H), 7.48–7.62 (m, 3H), 7.38–7.48 (m, 2H), 7.29–7.38 (m, 1H), 6.07–6.17 (m, 1H),
3.59–3.77 (m, 1H), 3.44–3.58 (m, 1H). 13C-NMR (CDCl3)
198.52 (C=O), 169.95 (C=O), 149.27, 137.93,
δ (ppm) 7.85–7.95
˝
1
δ
134.30, 132.65, 131.31, 30.77, 129.64, 129.49, 127.21, 125.90, 125.82, 122.45, 76.79, 47.74. MS (ESI m/z)
286.9 [M]+.
˝
3-(2-(4-Bromophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4e). White powder, yield 45%, m.p. 144–146 C
(lit. 147–149 ˝C [42]). IR (KBr) cm´1 1679 (C=O), 1740 (C=O). 1H-NMR (CDCl3):
(ppm) 7.86–7.98
(m, 1H), 7.74–7.86 (m, 2H), 7.58–7.73 (m, 3H), 7.47–7.58 (m, 2H), 6.14 (t, J = 6.5 Hz, 1H), 3.71
(ddd, J = 17.7, 6.0, 1.4 Hz, 1H), 3.35 (ddd, J = 17.5, 7.0, 1.4 Hz, 1H). 13C-NMR (CDCl3)
195.00
δ
δ
(C=O), 169.98 (C=O), 149.51, 134.88, 134.31, 132.19, 129.64, 129.53, 129.22, 125.89, 125.83, 122.69, 76.79,
43.63. MS (ESI m/z) 331.1 [M]+.

Molecules 2016, 21, 967
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˝
3-(2-(3-Bromophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4f). White crystals, yield 75%, m.p. 127–129 C
(lit. 124–127 C [52]). IR (KBr) cm´1 1688 (C=O), 1729 (C=O). H-NMR (CDCl3):
t, J = 1.8 Hz, 1H), 7.89–7.96 (m, 1H), 7.79–7.89 (m, 1H), 7.69–7.79 (m, 1H), 7.60–7.69 (m, 1H), 7.48–7.60
(m, 2H), 7.30–7.45 (m, 1H), 6.15 (t, J = 6.4 Hz, 1H), 3.68–3.80 (m, 1H), 3.37 (dd, J = 17.7, 7.1 Hz, 1H).
13C-NMR (CDCl3)
194.68 (C=O), 169.95 (C=O), 149.45, 137.82, 136.71, 134.32, 131.20, 130.42, 129.55,
126.70, 125.89, 125.84, 123.23, 122.67, 76.79, 43.77. MS (ESI m/z) 332.8 [M]+.
δ (ppm) 8.08
˝
1
(
δ
˝
3-(2-(2-Bromophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4g). White powder, yield 67%, m.p. 107–108 C
IR (KBr) cm´1 1684 (C=O), 1749 (C=O). 1H-NMR (CDCl3):
(ppm) 7.78–7.97 (m, 1H), 7.63–7.78 (m, 1H),
7.49–7.63 (m, 3H), 7.42–7.49 (m, 1H), 7.34–7.42 (m, 1H), 7.31 (td, J = 7.8, 1.8 Hz, 1H), 6.03–6.17 (m, 1H),
3.61 (dd, J = 17.7, 6.6 Hz, 1H), 3.41–3.54 (m, 1H). 13C-NMR (CDCl3)
199.38 (C=O), 169.88 (C=O),
.
δ
δ
149.14, 140.13, 134.27, 133.90, 132.37, 129.47, 129.11, 127.65, 125.81, 125.73, 122.47, 118.87, 76.78, 47.25.
MS (ESI m/z) 329.0 [M]+. Anal. Calcd. For: C16H11BrO3: C, 58.03; H, 3.35%. Found: C, 57.85; H, 3.59%.
˝
3-(2-(4-Fluorophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4h). White powder, yield 81%, m.p. 135–136 C
(lit. 130–133 ˝C [52]). IR (KBr) cm´1 1680 (C=O), 1745 (C=O). 1H-NMR (CDCl3):
(ppm) 7.94–8.06
(m, 2H), 7.91 (dd, J = 7.6, 1.1 Hz, 1H), 7.60–7.72 (m, 1H), 7.50–7.60 (m, 2H), 7.12–7.23 (m, 2H), 6.15
t, J = 6.5 Hz, 1H), 3.73 (dd, J = 17.5, 5.8 Hz, 1H), 3.36 (dd, J = 17.7, 7.1 Hz, 1H). 13C-NMR (CDCl3)
δ
(
δ
194.40 (C=O), 170.03 (C=O), 167.01, 149.59, 134.30, 132.65, 130.93, 130.86, 129.50, 125.89, 125.80, 122.74,
116.10, 115.95, 76.79, 43.60. MS (ESI m/z) 268.3 [M]+.
˝
3-(2-(3-Fluorophenyl)-2-oxoethyl)isobenzofuran-1(3H)-one (4i). White powder, yield 62%, m.p. 116–117 C
˝
´1
(lit. 114 C [47]). IR (KBr) cm 1684 (C=O), 1744 (C=O). 1H-NMR (CDCl3):
δ (ppm) 7.86–8.02 (m, 2H),
7.61–7.74 (m, 1H), 7.49–7.61 (m, 3H), 7.20–7.34 (m, 1H), 7.10–7.20 (m, 1H), 6.12–6.22 (m, 1H), 3.66–3.81
(m, 1H), 3.45 (dd, J = 6.4, 3.2 Hz, 1H). 13C-NMR (CDCl3) δ 193.92 (C=O), 170.11 (C=O), 163.04, 161.34,
149.62, 135.50, 134.23, 130.68, 129.40, 126.00, 125.78, 124.74, 122.60, 116.20, 76.79, 48.44. MS (ESI m/z)
268.8 [M]+.
˝
3-(2-Oxo-2-(m-tolyl)ethyl)isobenzofuran-1(3H)-one (4j). White powder, yield 56%, m.p. 108–109 C
(lit. 104–105 ˝C [47]). IR (KBr) cm´1 1676 (C=O), 1768 (C=O). 1H-NMR (CDCl3):
(ppm) 7.85–7.96
(m, 1H), 7.69–7.82 (m, 2H), 7.60–7.69 (m, 1H), 7.47–7.60 (m, 2H), 7.31–7.47 (m, 2H), 6.17 (dd, J = 7.6,
5.7 Hz, 1H), 3.76 (dd, J = 17.7, 5.7 Hz, 1H), 3.32–3.44 (m, 1H), 2.40 (s, 3H). 13C-NMR (CDCl3)
196.23
δ
δ
(C=O), 170.13(C=O), 149.81, 138.71, 136.22, 134.63, 134.24, 129.40, 128.69, 128.66, 125.74, 125.39, 122.83,
76.79, 43.76, 21.32. MS (ESI m/z): 265.1 [M]+.
˝
3-(2-Oxo-2-(o-tolyl)ethyl)isobenzofuran-1(3H)-one (4k). White powder, yield 63%, m.p. 102–103 C.
1
IR (KBr) cm´1 1688 (C=O), 1740 (C=O). H-NMR (CDCl3):
δ (ppm) 7.88–7.99 (m, 1H), 7.75–7.88
(m, 2H), 7.60–7.74 (m, 1H), 7.48–7.60 (m, 2H), 7.21–7.33 (m, 2H), 6.10–6.22 (m, 1H), 3.75 (dd, J = 17.5,
5.6 Hz, 1H), 3.35 (dd, J = 17.5, 7.5 Hz, 1H), 2.41 (s, 3H). 13C-NMR (CDCl3)
δ
199.24 (C=O), 170.10 (C=O),
149.71, 139.00, 136.45, 134.24, 132.33, 132.21, 129.41, 128.97, 125.96, 125.91, 125.80, 122.58, 76.79, 46.15,
21.63. MS (ESI m/z) 264.6 [M]+. Anal. Calcd. For: C17H14O3: C, 76.68; H, 5.30%. Found: C, 76.53;
H, 5.22%.
3-(2-(3-Methoxyphenyl)-2-oxethyl)isobenzofuran-1(3H)-one (4l).
White powder, yield 68%, m.p.
110–111 C (lit. 134–135 C [42]). IR (KBr) cm´1 1676 (C=O), 1768 (C=O). H-NMR (CDCl3):
(ppm) 7.91 (dd, J = 7.7, 1.0 Hz, 1H), 7.60–7.80 (m, 1H), 7.48–7.60 (m, 4H), 7.30–7.44 (m, 1H), 7.13
dd, J = 8.3, 2.5, Hz, 1H), 6.14–6.22 (m, 1H), 3.85–4.02 (m, 3H), 3.73–3.79 (m, 1H), 3.35–3.44 (m, 1H).
13C-NMR (CDCl3)
196.23 (C=O), 170.13(C=O), 149.81, 138.71, 136.22, 134.63, 134.24, 129.40, 128.69,
128.66, 125.74, 125.39, 122.83, 76.79, 43.76, 21.32. MS (ESI m/z) 265.1 [M]+.
δ
˝
˝
1
(
δ
˝
3-(2-Oxo-2-(thiophen-2-yl)ethyl)isobenzofuran-1(3H)-one (4m). White powder, yield 54%, m.p. 125–127 C
(lit. 125–127 C) [49]. IR (KBr) cm´1 1645 (C=O), 1767 (C=O). H-NMR (CDCl3):
d, J = 7.6 Hz, 1H), 7.73–7.84 (m, 1H), 7.58–7.73 (m, 2H), 7.48–7.58 (m, 1H), 7.32–7.48 (m, 1H), 7.19–7.32
(m, 1H), 7.02–7.19 (m, 1H), 6.11 (t, J = 6.5 Hz, 1H), 3.60–3.79 (m, 1H), 3.38–3.57 (m, 1H). 13C-NMR
δ (ppm) 7.90
˝
1
(

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(CDCl3)
δ 188.73 (C=O), 170.18 (C=O), 149.50, 143.44, 134.99, 134.46, 133.07, 129.61, 128.57, 125.84,
122.80, 44.18. MS (ESI m/z) 256.8 [M]+.
3.3. General Procedure for the Synthesis of Benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-ones 5a–5m
3-(2-Oxo-2-phenylethyl)isobenzofuran-1(3H)-ones 4a
2-aminobenzylamine (8.0
10´3 mol) dissolved in toluene (40 mL). To the mixture was added
p-toluenesulfonic acid monohydrate (70 mg; 3.5
10´4 mol) as a catalyst. The mixture was refluxed
–
4m (4.0
ˆ
10´3 mol) were added to
ˆ
ˆ
with stirring for 24 h and the reaction monitored using TLC. The solution was left to cool to room
temperature and the excess solvent was removed on a rotary evaporator. The resulting solid was
filtered, dried and recrystallized from ethanol.
(E)-6-Phenyl-7,7a-dihydrobe˝nzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5a). Light yellow crystals,
1
yield 74%, m.p. 203–204 C. IR (KBr) cm´1 1700 (C=O), 1623 (C=N). H-NMR (CDCl3):
δ (ppm)
8.12–8.21 (m, 2H), 7.83 (d, J = 7.2 Hz, 1H), 7.76 (dd, J = 7.7, 1.5 Hz, 1H), 7.51–7.64 (m, 4H), 7.37–7.51
(m, 2H), 7.22–7.33 (m, 1H), 7.07–7.16 (m, 1H), 7.01 (dd, J = 7.7, 1.2 Hz, 1H), 5.25–5.34 (m, 1H), 4.53
(
d, J = 10.7 Hz, 1H), 3.60–3.74 (m, 2H), 2.25–2.35 (m, 1H). 13C-NMR (CDCl3)
δ 167.16, 165.68, 148.78,
143.90, 137.18, 132.62, 131.78, 131.64, 131.42, 129.13, 129.00, 128.84, 128.80, 127.80, 127.74, 126.16, 125.09,
123.99, 121.91, 121.14, 56.11, 42.02, 36.28. MS (ESI m/z) 339.3 [M]+. Anal. Calcd. For: C23H18N2O: C,
81.63; H, 5.36; N, 8.28%. Found: C, 81.55; H, 5.66; N, 8.21%.
(E)-6-(4-Chlorophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5b). Light yellow
crystals, yield 75%, m.p. 198–199 ˝C. IR (KBr) cm´1 1695 (C=O), 1653 (C=N). 1H-NMR (CDCl3):
δ
(ppm) 8.10 (d, J = 8.3 Hz, 2H), 7.78–7.88 (m, 1H), 7.65–7.78 (m, 1H), 7.50–7.64 (m, 4H), 7.46 (ddd, J = 7.8
,
6.0, 2.3 Hz, 1H), 7.22–7.34 (m, 1H), 7.07–7.17 (m, 1H), 6.96–7.05 (m, 1H), 5.29 (d, J = 14.7 Hz, 1H), 4.50
(d, J = 10.5 Hz, 1H), 3.64 (d, J = 14.2 Hz, 1H), 3.57 (d, J = 13.3 Hz, 1H), 2.28 (dd, J = 13.8, 11.0 Hz, 1H).
13C-NMR (CDCl3)
δ 167.13, 164.43, 148.50, 143.69, 137.76, 135.58, 132.59, 131.85, 131.68, 129.40, 129.34,
129.08, 129.04, 128.94, 128.84, 126.08, 125.28, 124.07, 121.84, 121.14, 56.30, 42.00, 36.19. MS (ESI m/z)
373.2 [M]+. Anal. Calcd. For: C23H17ClN2O: C, 74.09; H, 4.60; N, 7.51%. Found: C, 73.85; H, 4.50;
N, 7.45%.
(E)-6-(3-Chlorophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5c). Light yellow
crystals, 73%, m.p. 107–108 ˝C. IR (KBr) cm´1 1699 (C=O), 1653 (C=N). 1H-NMR (CDCl3):
δ (ppm)
8.18 (t, J = 2.1 Hz, 1H), 8.00 (dt, J = 7.8, 1.4 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.74 (dd, J = 7.7, 1.5 Hz, 1H),
7.43–7.62 (m, 5H), 7.22–7.35 (m, 1H), 7.13 (td, J = 7.6, 1.4 Hz, 1H), 7.00 (dd, J = 7.9, 1.4 Hz, 1H), 5.30
(
d, J = 14.4 Hz, 1H), 4.51 (d, J = 10.7 Hz, 1H), 3.65 (d, J = 14.4 Hz, 1H), 3.57 (dd, J = 13.7, 1.4 Hz, 1H),
2.28 (dd, J = 13.6, 10.8 Hz, 1H). 13C-NMR (CDCl3)
δ
167.03, 164.24, 148.26, 143.57, 138.90, 135.35, 132.47,
131.77, 131.59, 131.27, 130.20, 128.85, 128.77, 127.95, 125.93, 125.56, 125.29, 123.97, 121.80, 121.00, 56.13,
41.89, 36.23. MS (ESI m/z) 373.2 [M]+. Anal. Calcd. For: C23H17ClN2O: C, 74.09; H, 4.60; N, 7.51%.
Found: C, 74.20; H, 4.55; N, 7.50%.
(E)-6-(2-Chlorophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5d). Light brown
crystals, yield 73%, m.p. 191–192 ˝C. IR (KBr) cm´1 1685 (C=O), 1552 (C=N). 1H-NMR (CDCl3,):
δ
(ppm) 7.74–7.87 (m, 1H), 7.31–7.50 (m, 5H), 7.18–7.31 (m, 2H), 6.99–7.18 (m, 2H), 6.56–6.74 (m, 2H),
4.98–5.15 (m, 2H), 4.37 (d, J = 15.1 Hz, 1H), 3.75 (dd, J = 17.5, 3.8 Hz, 1H), 3.23 (dd, J = 17.4, 8.1 Hz, 1H).
13C-NMR (CDCl3)
δ 168.49, 167.14, 147.49, 143.58, 139.17, 132.35, 131.77, 131.60, 131.53, 130.83, 130.71,
130.19, 128.77, 128.65, 127.34, 126.00, 125.50, 123.76, 122.03, 121.20, 55.05, 41.81, 40.23. MS (ESI m/z)
373.2 [M]+. Anal. Calcd. For: C23H17ClN2O: C, 74.09; H, 4.60; N, 7.51%. Found: C, 74.00; H, 4.55;
N, 7.50%.
(E)-6-(4-Bromophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5e). Light yellow
crystals, yield 85%, m.p. 196–197 ˝C. IR (KBr) cm´1 1691 (C=O), 1662 (C=N). 1H-NMR (CDCl3):
δ
(ppm) 7.68–7.88 (m, 2H), 7.51–7.68 (m, 2H), 7.33–7.51 (m, 4H), 7.20–7.33 (m, 2H), 7.14 (td, J = 7.6,
1.4 Hz, 1H), 7.03 (dd, J = 7.9, 1.4 Hz, 1H), 5.38 (d, J = 14.8 Hz, 1H), 4.46 (d, J = 10.7 Hz, 1H), 4.02

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(
d, J = 14.4 Hz, 1H), 3.51 (dd, J = 13.2, 1.5 Hz, 1H), 2.35 (dd, J = 13.2, 11.2 Hz, 1H). 13C-NMR (CDCl3)
δ
167.05, 164.48, 148.39, 143.58, 135.93, 134.33, 132.47, 132.23, 132.04, 131.76, 131.58, 129.46, 129.14, 128.85,
128.76, 127.49, 125.20, 121.75, 121.56, 121.01, 56.19, 41.90, 36.05. MS (ESI m/z) 417.1[M]+. Anal. Calcd.
For: C23H17BrN2O: C, 66.20; H, 4.11; N, 6.71%. Found: C, 66.22; H, 4.11; N, 6.70%.
(E)-6-(3-Bromophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5f). White crystals,
yield 72%, m.p. 219–220 ˝C. IR (KBr) cm´1 1698 (C=O), 1625 (C=N). 1H-NMR (CDCl3):
δ (ppm) 8.34
(t, J = 1.8 Hz, 1H), 8.01–8.10 (m, 1H), 7.81 (d, J = 7.3 Hz, 1H), 7.66–7.78 (m, 2H), 7.52–7.65 (m, 2H),
7.37–7.52 (m, 2H), 7.22–7.35 (m, 1H), 7.10–7.18 (m, 1H), 6.98–7.09 (m, 1H), 5.29 (d, J = 14.7 Hz, 1H), 4.51
(d, J = 10.5 Hz, 1H), 3.65 (d, J = 14.7 Hz, 1H), 3.56 (d, J = 13.8 Hz, 1H), 2.28 (dd, J = 13.8, 11.0 Hz, 1H).
13C-NMR (CDCl3)
δ 167.12, 164.23, 148.35, 143.66, 139.20, 134.29, 132.57, 131.88, 131.69, 131.02, 130.54,
128.96, 128.87, 126.09, 125.95, 125.40, 124.06, 123.57, 121.89, 121.11, 56.22, 41.99, 36.30. MS (ESI m/z)
417.1 [M]+. Anal. Calcd. For: C23H17BrN2O: C, 66.20; H, 4.11; N, 6.71%. Found: C, 66.15; H, 4.10;
N, 6.65%.
(E)-6-(2-Bromophenyl)-7,7a-dihydrobenz[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5g). Colourless
˝
1
needles, yield 27%, m.p. 137–138 C. IR (KBr) cm´1 1683 (C=O), 1653 (C=N). H-NMR (CDCl3):
δ
(ppm) 7.78–7.85 (m, 1H), 7.53–7.63 (m, 1H), 7.36–7.52 (m, 3H), 7.20–7.34 (m, 2H), 7.06–7.20 (m, 3H),
6.59–6.70 (m, 2H), 5.00–5.12 (m, 2H), 4.38 (d, J = 15.5 Hz, 1H), 3.74 (dd, J = 17.7, 3.6 Hz, 1H), 3.22
dd, J = 17.5, 7.9 Hz, 1H). 13C-NMR (CDCl3)
168.75, 145.90, 145.47, 140.60, 133.83, 132.12, 131.92,
(
δ
131.31 130.95, 129.54, 128.71, 128.50, 127.52, 123.79, 122.92, 119.63, 117.21, 115.75, 55.88, 44.71, 42.10. MS
(ESI m/z) 419.1 [M]+. Anal. Calcd. For: C23H17BrN2O: C, 66.20; H, 4.11; N, 6.71%. Found: C, 66.15; H,
4.05; N, 6.58%.
(E)-6-(4-Fluorophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5h). Colourless
needles, yield 72%, m.p. 136–137 ˝C. IR (KBr) cm´1 1696 (C=O), 1662 (C=N). 1H-NMR (CDCl3):
δ
(ppm) 8.17 (dd, J = 8.9, 5.3 Hz, 2H), 7.81 (d, J = 7.8 Hz, 1H), 7.66–7.78 (m, 1H), 7.52–7.66 (m, 2H),
7.37–7.52 (m, 1H), 7.22–7.37 (m, 3H), 7.05–7.17 (m, 1H), 6.97–7.05 (m, 1H), 5.29 (d, J = 14.2 Hz, 1H), 4.51
(d, J = 10.5 Hz, 1H), 3.66 (d, J = 14.2 Hz, 1H), 3.58 (d, J = 13.8 Hz, 1H), 2.29 (dd, J = 13.5, 10.8 Hz, 1H).
13C-NMR (CDCl3)
δ 167.13, 164.80, 164.35, 148.58, 143.75, 133.38, 132.60, 131.782, 131.66, 129.92, 129.86,
128.92, 128.83, 126.14, 125.19, 124.06, 121.84, 121.19, 116.23, 116.09, 56.33, 42.01, 36.24. MS (ESI m/z)
557.3 [M]+. Anal. Calcd. For: C23H17FN2O: C, 77.51; H, 4.81; N, 7.86%. Found: C, 77.34; H, 4.85;
N, 7.76%.
(E)-6-(3-Fluorophenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5i). Colourless
crystals, yield 55%, m.p. 187–189 ˝C. IR (KBr) cm´1 1701 (C=O), 1620 (C=N). 1H-NMR (CDCl3):
δ
(ppm) 8.12–8.20 (m, 2H), 7.81 (d, J = 7.2 Hz, 1H), 7.66–7.78 (m, 1H), 7.51–7.63 (m, 4H), 7.41–7.51 (m, 1H),
7.23–7.33 (m, 1H), 7.07–7.16 (m, 1H), 6.97–7.05 (m, 1H), 5.29 (d, J = 14.4 Hz, 1H), 4.53 (d, J = 11.0 Hz,
1H), 3.60–3.74 (m, 2H), 2.28 (dd, J = 13.6, 10.8 Hz, 1H). 13C-NMR (CDCl3)
δ 168.78, 163.25, 167.15,
162.80, 147.68, 146.09, 145.87, 143.98, 131.87, 135.21, 131.69, 131.36, 130.90, 129.41, 128.35, 123.74, 122.91,
117.38, 115.69, 55.59, 45.80, 41.91. MS (ESI m/z) 357.3 [M]+. Anal. Calcd. For: C23H17FN2O: C, 77.51; H,
4.81; N, 7.86%. Found: C, 77.45; H, 4.75; N, 7.75%.
(E)-6-(m-Tolyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5j). Colourless crystals,
yield 68%, m.p. 150–151 ˝C. IR (KBr) cm´1 1706 (C=O), 1680 (C=N); 1H-NMR (CDCl3):
δ
(ppm) 7.89
(d, J = 7.6 Hz, 2H), 7.52–7.70 (m, 3H), 7.09–7.21 (m, 2H), 6.93 (td, J = 7.5, 1.2 Hz, 1H), 6.80 (d, J = 7.9 Hz
2H), 5.51 (d, J = 4.1 Hz, 1H), 5.21 (d, J = 17.2 Hz, 1H), 4.57 (d, J = 16.8 Hz, 1H), 4.12–4.30 (m, 1H), 3.48
(s, 2H), 0.95–1.13 (m, 1H). 13C-NMR (CDCl3)
166.38, 149.79, 148.69, 143.84, 132.14, 131.85, 131.51,
,
δ
128.83, 128.70, 128.42, 126.07, 125.73, 125.39, 124.96, 124.64, 124.13, 123.88, 122.81, 121.14, 55.59, 45.80,
41.91, 21.31. MS (ESI m/z) 353.3 [M]+. Anal. Calcd. For: C24H20N2O: C, 81.79; H, 5.72; N, 7.95%.
Found: C, 81.54; H, 5.53; N, 7.68%.
(E)-6-(o-Tolyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5k). Light yellow crystals,
yield 40%, m.p. 155–156 ˝C. IR (KBr) cm´1 1687 (C=O), 1298 (C-O), 1623 (C=N). 1H-NMR (CDCl3):

Molecules 2016, 21, 967
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δ
(ppm) 8.05 (d, J = 8.2 Hz, 2H), 7.77–7.88 (m, 2H), 7.73 (dd, J = 7.6, 1.7 Hz, 1H), 7.50–7.61 (m, 1H),
7.40–7.50 (m, 2H), 7.36 (d, J = 8.2 Hz, 1H), 7.21–7.32 (m, 1H), 7.10 (td, J = 7.6, 1.4 Hz, 1H), 7.00 (dd, J = 7.7
1.2 Hz, 1H), 5.27 (d, J = 14.4 Hz, 1H), 4.52 (d, J = 10.7 Hz, 1H), 3.68 (d, J = 14.4 Hz, 1H), 3.61 (dd, J = 13.7
,
,
1.4 Hz, 1H), 2.43–2.54 (m, 3H), 2.26 (dd, J = 13.6, 10.8 Hz, 1H). 13C-NMR (CDCl3)
δ
167.08, 165.44, 148.78,
143.86, 141.81, 134.22, 131.66, 131.50, 129.72, 129.38, 128.67, 128.27, 127.63, 126.14, 125.71, 124.85, 123.87,
122.84, 121.80, 121.17, 56.44, 41.92, 36.06, 21.43. MS (ESI m/z) 353.3. Anal. Calcd. For: C24H20N2O: C,
81.79; H, 5.72; N, 7.95%. Found: C, 81.50; H, 5.58; N, 7.90%.
(E)-6-(3-Methoxyphenyl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5l). Light yellow
crystals, yield 62%, m.p. 210–211 ˝C. IR (NKBr) cm´1 1692 (C=O), 1265 (C-O), 1616 (C=N). 1H-NMR
(CDCl3):
7.38–7.52 (m, 3H), 7.22–7.34 (m, 1H), 7.06–7.17 (m, 1H), 7.01 (dd, J = 7.9, 1.4 Hz, 1H), 5.29 (d, J = 14.4 Hz
1H), 4.54 (d, J = 10.7 Hz, 1H), 3.92 (s, 3H), 3.69 (d, J = 14.4 Hz, 1H), 3.61 (dd, J = 13.7, 1.4 Hz, 1H), 2.27
(dd, J = 13.6, 10.8 Hz, 1H). 13C-NMR (CDCl3)
167.06, 165.36, 160.20, 148.62, 143.81, 138.49, 132.51,
δ (ppm) 7.80 (d, J = 7.6 Hz, 1H), 7.71–7.78 (m, 2H), 7.63–7.71 (m, 1H), 7.52–7.63 (m, 2H),
,
δ
131.70, 131.55, 129.91, 128.73, 128.70, 126.08, 125.01, 123.88, 121.82, 121.08, 119.90, 117.40, 112.80, 56.40,
55.50, 41.92, 36.29. MS (ESI m/z) 369.3 [M]+. Anal. Calcd. For: C24H20N2O2: C, 78.24; H, 5.47; N, 7.60%.
Found: C, 78.15; H, 5.45; N, 7.55%.
(E)-6-(Thiophen-2-yl)-7,7a-dihydrobenzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one (5m). Light yellow
crystals, yield 32%, m.p. 279–280 ˝C. IR (KBr) cm´1 1694 (C=O), 1661 (C=N). 1H-NMR (CDCl3):
δ
(ppm) 7.78–7.86 (m, 1H), 7.33–7.52 (m, 3H), 7.15–7.30 (m, 2H), 7.04–7.15 (m, 2H), 6.56–6.69 (m, 2H),
4.95–5.13 (m, 2H), 4.36–4.54 (m, 1H), 3.67–3.78 (m, 1H), 3.21 (dd, J = 17.4, 8.0 Hz, 1H). 13C-NMR (CDCl3)
δ
167.10, 160.69, 144.47, 143.90, 143.73, 132.62, 131.82, 131.66, 131.50, 128.90, 128.77, 128.50, 128.09,
126.80, 125.34, 124.04, 121.90, 121.61, 56.95, 42.08, 37.31. MS (ESI m/z) 345.2 [M]+. Anal. Calcd. For:
C21H16N2OS: C, 73.23; H, 4.68; N, 8.13%. Found: C, 73.05; H, 4.55; N, 8.05%.
4. Conclusions
In conclusion, we have developed a simple two-step synthetic route to the benzo[6,7][1,5]diazocino
[2,1-a]isoindole fused ring system from readily available starting materials. A number of
3-(2-oxo-2-phenylethyl)isobenzofuran-1(3H)-ones 4a
2-aminobenzylamine under para-toluenesulfonic acid catalysis to yield the fused diazocine derivatives
5a 5m in 27%–85% yields. The structure of the regioisomer formed has been confirmed unambiguously
–4m were reacted in boiling toluene with
–
by rigorous multinuclear HMBC measurements. Biological evaluation of the synthesized compounds
are currently under investigation and will be reported in future communications.
Supplementary Materials: The following are available online at www.mdpi.com/1420-3049/21/8/967/s1.
Acknowledgments: Authors are grateful to Virendra P. Shah for assistance with some of the synthetic work.
The authors are grateful to the University of Hertfordshire for providing funds for Open Access.
Author Contributions: J.P.B., M.G., C.B., B.A. and M.H. planned, designed and carried out the synthetic work,
discussed results, wrote and reviewed the manuscript. U.G. contributed with the collection and analysis of the
spectral data and contributed in the preparation of the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 4a–4m and 5a–5m are available from the authors.
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