The chemical and structural properties of 2-aminobenzylamine derivatives

Article abstract of DOI:10.5560/ZNB.2013-3107

We report a conventional and simple method to synthesize quinazoline and benzodiazepine derivatives by treatment of 2-aminobenzylamine (1) with several π-electron-deficient compounds. Quinazoline derivatives were obtained by treatment of 1 with either tetracyanoethylene or 7,7,8,8- tetracyanoquinodimethane. Benzodiazepine derivatives were formed when 1 was reacted with either 2,3-dichloro-1,4-naphthoquinone or 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone. Fused quinazoline and benzoazepine derivatives were formed by dry heating of 1 with either naphthalic anhydride, cis-1,2,3,6- tetrahydrophthalic anhydride, tetrachlorophthalic anhydride and/or diphenic anhydride, respectively. The NMR spectra and the mass spectrometric data as well as elemental analyses of all new products are consistent with the proposed structures. The structures of the quinazoline derivatives 26 and 28 were further confirmed by single-crystal X-ray structure determination. Plausible mechanisms for the formation of several products are discussed.

Full text of DOI:10.5560/ZNB.2013-3107

The Chemical and Structural Properties of 2-Aminobenzylamine
Derivatives
Kamal M. El-Shaieba and Peter G. Jonesb
a
Chemistry Department, Faculty of Science, Minia University, El-Minia, A. R. Egypt
Institute of Inorganic and Analytical Chemistry, Hagenring 30, Technische Universita¨t
b
Braunschweig, D-38106 Braunschweig, Germany
Reprint requests to Dr. Kamal M. El-Shaieb. Fax: +2-086-2342601.
E-mail: kmelshaieb@yahoo.com
Z. Naturforsch. 2013, 68b, 913 – 923 / DOI: 10.5560/ZNB.2013-3107
Received April 8, 2013
We report a conventional and simple method to synthesize quinazoline and benzodiazepine deriva-
tives by treatment of 2-aminobenzylamine (1) with several π-electron-deficient compounds. Quin-
azoline derivatives were obtained by treatment of 1 with either tetracyanoethylene or 7,7,8,8-tetra-
cyanoquinodimethane. Benzodiazepine derivatives were formed when 1 was reacted with either 2,3-
dichloro-1,4-naphthoquinone or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. Fused quinazoline and
benzoazepine derivatives were formed by dry heating of 1 with either naphthalic anhydride, cis-
1,2,3,6-tetrahydrophthalic anhydride, tetrachlorophthalic anhydride and/or diphenic anhydride, re-
spectively. The NMR spectra and the mass spectrometric data as well as elemental analyses of all
new products are consistent with the proposed structures. The structures of the quinazoline deriva-
tives 26 and 28 were further confirmed by single-crystal X-ray structure determination. Plausible
mechanisms for the formation of several products are discussed.
Key words: 2-Aminobenzylamine, π Acceptors, Anhydrides, Quinazolines, Diazepines
Introduction
them are for example widely used as antileukaemic, an-
tiplatelet, anticonvulsant, and neuroleptic agents [12].
Nitrogen-containing heterocycles are an important Some heterocycles containing benzodiazepine moi-
class of compounds in medicinal chemistry [1]. There eties were also found to have anti-inflammatory, an-
has been considerable interest in the development of re- tiviral, anti-HIV-1, antimicrobial, and antitumour ac-
liableandsimplepreparativemethodsfortheproduction tivities [13]. Apart from their biological importance,
of quinazolines [2], because they and their ring-fused benzodiazepines are valuable synthons for the prepa-
derivatives display a broad spectrum of biological ac- ration of fused ring compounds, such as triazolo, thia-
tivities [3 – 5], like e. g. antitubercular, analgesic, anti- zolo, imidazo and pyrimidobenzo-diazepines [14]. Al-
inflammatory, and anti-bacterial, analgesic, and many though many methods for synthesizing benzodiazepine
other properties. These examples clearly demonstrate ring systems have been reported, they continue to re-
the remarkable potential of quinazoline derivatives as ceive much attention [11]. We found that reaction
a source of useful pharmacophores for new drug devel- of either 2,3-dichloro-1,4-naphthoquinone (DCHNQ)
opment.Substitutedquinazolineshavebeensynthesized or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
by a number of methods involving several substrates with 2-amino-N0-arylbenzamidines led to the formation
such as 2-amino-N0-aryl-benzamidines [6 – 8] and 2- of benzodiazepine derivatives via charge-transfer (CT)
aminobenzylamine [9, 10]. A further important class of complexes [15]. The formation of CT complexes has
heterocyclesisfurnishedbybenzodiazepines[11]. Ben- long been recognized as an important phenomenon in
zodiazepine derivatives are widely distributed in nature, many chemical processes [16], and this approach led us
and they represent a class of heterocycles which pos- tosynthesizeseveralheterocyclicsystemsthatcouldnot
sesses a wide range of biological applications. Many of be obtained by usual methods [17].
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
Results and Discussion
blet at δ = 4.38 ppm is assigned to the aliphatic CH2
protons with a coupling constant of J = 1.00 Hz. The
On continuing our studies in electron donor- l3C NMR spectrum showed signals from eleven dis-
acceptor interactions (EDA) as well as develop- tinct carbon atoms, two of them at δ = 119.16 and
ing conventional approaches for the synthesis of N- 117.62 ppm characteristic of cyano groups. The signal
heterocycles, we reported very recently highly ef- at δ = 41.12 ppm was assigned to the carbon atom of
ficient approaches for the synthesis of quinazo- the CH2 group. Both MS and elemental analysis con-
line [6 – 8] and benzodiazepine [12] derivatives. The firm the molecular formula of 6 as C11H8N4.
study was initiated by investigating the reaction of 2-
The 1H NMR of compound 7 reveals, in addition
aminobenzylamine (1) with the acceptors 2, 5, 8, and to the three multiplets assignable to the NH group and
11. We have found that treatment of 1 with TCNE 5 aromatic protons, a singlet at δ = 4.73 ppm for the two
and/or TCNQ 11 in anhydrous ethyl acetate leads to the aliphatic methylene protons. The IR spectrum shows
formation of deep-red or green complexes. The color bands at ν = 3278 and 2180 cm−1 characteristic for
gradually disappears to give rise to the formation of NH and CN, respectively. Formation of the quinazo-
the quinazoline derivatives 6, 7 and 12, respectively, lines 6 and 7 is suggested to proceed according to the
in excellent yield (Scheme 1). The assigned molecular mechanism outlined in Schemes 2 and 3. In this case
structures of the new compounds were based on spec- the reaction sequence would start by the formation of
troscopic analysis including IR, NMR, MS, and ele- the adducts 13 – 15. Losing a molecule of either HCN
mental analysis data.
or malononitrile furnishes the quinazolines 6 and 7, re-
The product 6 displayed in its IR spectrum strong spectively.
absorption maxima at ν = 3272 and 3218 cm−1 indi-
Addition of the electron donor 1 to the electron ac-
cating the presence of two different NH groups; the CN ceptor 11 in anhydrous ethyl acetate at room temper-
groups absorb at ν = 2207 and 2175 cm−1
.
ature led to an EDA complex with a deep-red color,
Furthermore, the IR spectrum reveals no absorption which gradually disappeared to give a single new re-
bands characteristic of NH2 groups. The 1H NMR action product 12 (TLC analysis). The mass spec-
spectrum of 6 exhibits, besides the signals from the trum and elemental analysis suggest the molecular
aromatic protons, two sharp singlets at δ = 10.26 and formula of 12 as C17H12N4. The IR spectrum of
8.32 ppm for the two different NH groups, and a dou- 12 shows sharp absorptions characteristic of differ-
N
NH
CN
N
H
CN
N
H
6
7
CN
Cl
NH
CN
5
NH
TCNE,
EtOAc/r. t., 7 h
97 %
NH2
O
O
N
N
3
9
DCHNQ, 2
8
DDQ,
EtOAc/r. t., 9 h
88 %
EtOAc/r. t., 4 h
87 %
Cl
Cl
Cl
NH2
1
N
N
11
TCNQ,
EtOAc/r. t., 3 h
96 %
Cl
N
H
N
H
4
10
NH
O
O
Cl
NC
N
H
12
CN
CN
Scheme 1. Reaction of 2-aminobenzylamine (1) with π-electron-deficient compounds.
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
915
NC
CN
CN
CN
..
CN
H
NH2
N
H
5
NC
CN
CN
NH2
1
NH2
−
13
HCN
NH
NH
NH
CN
CN
−
HCN
CN
CN
CN
. .
NH2
N
H
CN
H
6
N
H
14
15
CN
CN
Scheme 2. Mechanism for the formation of quinazoline derivative 6.
NC
CN
CN
CN
..
CN
NH 2
N
H
NC
CN
5
H
CN
NH2
1
NH2
−
HCN
13
H
N
N
NH
CN
CN
−
CH2 (CN)2
CN
CN
..
NH2
N
H
CN
N
H
7
15
H
14
CN
CN
Scheme 3. Mechanism for the formation of quinazoline derivative 7.
ent cyano groups at ν = 2185 and 2133 cm−1, and of bon appears at δ = 44.80 ppm. The brutto formula
the NH groups at ν = 3271, 3245 cm−1. Its 1H NMR C17H11ClN2O of 3 was confirmed by the mass spec-
spectrum reveals, apart from the aromatic protons, two trum, which exhibited the molecular ion at m/z = 294
broad singlets at δ = 11.51 and 10.12 ppm for the two (100%).
different NH groups; the cyclohexadiene protons ap-
Treatment of 1 with DDQ 7 in ethyl acetate led to
pear as two doublets at δ = 7.60 and 6.90 ppm with the dibenzodiazepine 8 rather than to its isomer 9, the
similar coupling constants of J = 8.81 Hz, and the evidence for which is related to the case of 3 and 4 (see
two aliphatic methylene protons as a singlet at δ = above). The IR spectrum of compound 8 showed three
4.76 ppm.
strong absorptions at ν = 3296, 2209 and 1663 cm−1
,
Benzonaphthodiazepine derivative 3 rather than 4 indicating the presence of NH, CN and CO groups, re-
is formed on stirring compound 1 with DCHNQ 2 in spectively. In the H NMR spectrum the NH group ap-
1
ethyl acetate at room temperature. One indication of peared as a triplet at δ = 9.85 ppm with J = 5.16 Hz,
this is the coupling between the methylene protons whereas the methylene protons form a doublet at δ =
(doublet at δ = 4.33 ppm with J = 5.25 Hz) and the 4.37 ppm with J = 5.27 Hz. The 13C NMR spectrum
adjacent sp3 NH proton (triplet at δ = 8.38 ppm with of 8 showed fourteen distinct resonances, of which
J = 5.10 Hz); in 4 both of the NH and methylene pro- those at δ = 172.15 and 45.24 ppm are assigned to
tons should appear as two different singlets. The IR the carbonyl and the methylene carbon atoms, respec-
spectrum of 3 displayed absorptions at ν = 3284 (NH) tively. The molecular formula of dibenzodiazepine 8
and 1630 cm−1 (CO). In its 13C NMR spectrum, the is supported by elemental analysis and the mass spec-
C=O and C=N carbon atoms appear at δ = 174.59 trum with the expected molecular ion peak as the base
and 151.14 ppm, respectively, while the methylene car- peak.
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
Heating of 1 with NQ 16 and/or BQ 18 in anhy- 3.76 and 3.70 ppm for the methyl ester protons and
drous ethyl acetate produced 17 and 19, respectively a doublet at δ = 3.94 ppm for the -NH–CH2- protons
(Scheme 4). The 1H NMR spectrum showed all the with J = 4.35 Hz. The 1H NMR spectrum of 21 dis-
expected signals; in addition to the aromatic signals played two doublets at δ = 3.05 and 2.85 ppm with
a triplet at δ ≈ 8.14 ppm for the NH protons, and a sin- similar coupling constants J = 15.63 Hz referred to
glet of two protons at δ ≈ 5.00 ppm for the NH2 pro- the AB spin system, along with characteristic reso-
tons were observed. In addition, a characteristic dou- nances for the four aromatic protons. The presence
blet at δ ≈ 4.20 ppm with a coupling constant J ≈ of the AB spin system in the 1H NMR spectrum in-
6.00 Hz for the methylene protons was noted. The IR dicates the formation of the product 21. As the re-
spectra showed bands at ν ≈ 3420, 3390, 3220 cm−1 sult of the expected instability of the benzodiazepine
for the NH2 and NH groups, whereas the carbonyl derivative 21, due to its angle strain, one can ex-
groups absorbed at ν ≈ 1670 and 1629 cm−1. Further- pect its rearrangement into the more stable quinazo-
more, the structure assigned for the products 17 and line derivative 22. Isomerization between 21 and 22
19 were fully supported by their mass spectra, which has been noticed and confirmed by measuring the
showed their molecular formulae C17H14N2O2 and NMR spectrum of the sample after 1 h. The data re-
C20H20N4O2, respectively.
veals the presence of a quaternary carbon atom res-
Heating of 1 with dimethyl acetylenedicarboxylate onating in the 13C NMR spectrum at δ = 70.63 ppm
(DMAD, 20) in anhydrous chloroform provides quin- characteristic for the NH–C–NH carbon atom, in ad-
azoline derivative 22, which might be in equilibrium dition to the presence of a signal at δ = 43.24 ppm
with its diazepine isomer 21 (Scheme 4). The results for the methylene carbon of the CH2CO2CH3 group.
1
obtained from elemental microanalysis and the IR, H The two carbonyl groups of the product have been
NMR, 13C NMR and mass spectroscopic data are in recorded in the 13C NMR spectrum at δ = 172.31 and
agreement with the assigned structure. The IR spec- 170.22 ppm. Furthermore, the methylene carbon atom
trum showed two strong absorptions at ν = 3362 and of the CH2NH group resonates at δ = 42.48 ppm,
1729 cm−1, indicating the presence of NH and CO and the methyl ester carbon atoms at δ = 52.92
groups, respectively. However, the 1H NMR spec- and 51.93 ppm. The mass spectrum of this sample
trum shows two broad resonances at δ = 4.88 and gives the molecular ion peak at m/z = 264 which is
2.60 ppm for the two exchangeable protons of the two in accordance with the molecular mass (264.11) of
NH groups. Moreover, there are two singlets at δ = compound 22.
O
NH2
HN
NH
H2N
19
O
18
1,4-benzo-quinone,
NH
..
EtOAc/refl., 3 h
NH2
94 %
H
CO2C
O
O
3
NH
NH2
H
1,4-napho
N
H
16
quinone,
21
H
CO2C
3
EtOAc
20
DMAD
,
-
− s
t
refl., 5 h
1 2 H hif
,
NH2
79
%
1
CHCl3/refl., 3 h
81 %
17
23
CHL-p,
NH
EtOAc/r. t., 5 h
98 %
H
CO2C
3
O
l
C
NH2
N
H
22
CO2CH3
H
N
N
H
H2N
l
C
O
24
Scheme 4. Reactions of 1 with CHL-p, NQ, BQ and DMAD.
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
917
N
N
28
O
O
O
O
fusion/5 min
74
%
27
NH2
Cl
O
O
O
Cl
Cl
O
O
O
N
O
Cl
29
l
C
O
N
25
fusion/5 min
NH2
fusion/5 min
91 %
N
95 %
N
2
6
1
l
C
30
l
C
fusion/5 min
69 %
l
C
O
O
31
O
O
N
N
32
Scheme 5. Reactions of compound 1 with selected anhydrides.
The substituted quinone 24 was obtained in excel- gate the reactivity of 1 towards electrophilic reagents
lent yield by the reaction of 2-amino-benzylamine (1) such as naphthalic anhydride, tetrahydrophthalic an-
with CHL-p 23 in absolute ethyl acetate at room tem- hydride, diphenic anhydride, and tetrachlorophthalic
perature (Scheme 4). The deep-green solution initally anhydride (Scheme 5). The conditions for the reac-
formed rapidly turned to yellowish green while a pre- tion between the reactant 1 and the anhydrides 25,
cipitate was formed. The structure of 24 was con- 27, 29, and 31 were investigated in a number of tri-
firmed by elemental analysis and spectral data. Three als, and the optimized conditions were identified by
IR bands at ν = 3421, 3349, 3326 cm−1 are assignable varying the reagent concentrations, the reaction time
to NH2 and NH groups, while the carbonyl group ap- and/or temperature. We found that the optimum con-
peared at ν = 1638 cm−1. In the 1H NMR spectrum ditions for this reaction involve mixing both reaction
the NH and NH2 protons appeared at δ = 8.18 and partners in equimolar amounts and heating them at
5.11 ppm, respectively; six multiplets in the region at 200 ◦C for 5 min. This reaction sequence is conve-
δ = 7.17 – 6.50 ppm are assigned to aromatic protons, niently performed in one-pot procedures without iso-
and a singlet at δ = 4.80 ppm to the methylene pro- lation of the intermediates. Previous studies on reflux-
tons. In the 13C NMR spectrum signals of most of the ing 1 with anhydride 27 in absolute EtOH afforded
carbon atoms of CH2, CH, C =O and the aromatic sys- a mixture of two products in low yields [18]. Thus
tem could be assigned and were in agreement with the when a mixture of 1 and anhydride 25 were dry heated
proposed structure (see spectral data in the Experimen- at 200 ◦C for 5 minutes, the quinazoline derivative 26
tal Section). Both mass spectrum and elemental analy- was formed as colorless crystals in excellent yield
sis confirm the molecular formula of the product 24 as (Scheme 5).
C20H18Cl2N4O2.
The structure of product 26 was corroborated by its
1
Recently, we have reported that diamino com- elemental analysis and IR, H and 13C NMR spectro-
pounds can be employed as key starting materi- scopic data. The mass spectrum of 26 displayed the
als for the synthesis of diverse nitrogen bridgehead molecular ion ( M+) at m/z = 238 as the base peak.
compounds [6 – 8, 15]. This prompted us to investi- The 1H NMR spectrum of 26 exhibited four differ-
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
Fig. 2. The molecular structure of 28 in the solid state with
the crystallographic numbering scheme adopted.
Fig. 1. The molecular structure of 26 in the solid state with
the crystallographic numbering scheme adopted.
ent multiplets at δ = 7.24 – 7.00 ppm for the aromatic confirmed the molecular formula C15H6Cl4N2O
protons, along with five different characteristic multi- (369.92).
plets for the six protons of the cyclohexene moiety at
The reactivity of 1 towards the anhydride 31 was
δ = 3.38 – 2.24 ppm. Furthermore, the methylene pro- also studied; as illustrated in Scheme 5 the reaction
ton resonated as a sharp singlet at δ = 4.79 ppm. The furnishes the dibenzoazepinoquinazoline 32. Its struc-
proton-decoupled 13C NMR spectrum of 26 showed ture was assigned on the basis of the NMR data and
14 distinct resonance lines in agreement with the pro- was supported by IR data. The 1H NMR spectrum of
posed structure. Unambiguous evidence for the pro- the quinazoline derivative 32 revealed six characteris-
posed structure of 26 was finally obtained by single- tic multiplets at δ = 7.68 – 6.55 ppm assigned to the
crystal X-ray-diffraction analysis as shown in Fig. 1.
twelve aromatic protons. Furthermore, a singlet was
Similarly, heating of 1 with naphthalic anhydride present at δ = 4.14 ppm due to the methylene pro-
(NA, 27) in the absence of solvents for 5 minutes at tons. The methylene carbon signal of 32 appeared in
200 ◦C afforded the quinazoline derivative 28 as or- the 13C NMR spectrum at δ = 40.78 ppm, and the car-
ange crystals in excellent yield as shown in Scheme 5. bonyl carbon atom resonated at δ = 175.11 ppm. The
The structure of the quinazoline derivative 28 was es- molecular formula of compound 32 is supported by el-
tablished by conventional spectroscopic methods as emental analysis and a mass spectrum that gave the ex-
well as elemental analysis. It exhibits two strong IR ab- pected molecular ion peak and fragmentation patterns
sorption bands at 1694 and 1623 cm−1 for the CO and (see Experimental Section).
C=N groups, respectively. The same carbon atoms res-
onated in the 13C NMR at δ = 171.16 and 160.73 ppm, Conclusion
respectively. The 1H NMR spectrum of 28 shows
characteristic signals in the aromatic region at δ =
Herein, we have reported a facile and efficient syn-
8.51 – 6.26 ppm. A singlet at δ = 5.06 ppm was as- thesis of substituted quinazoline and benzodiazepine
signed to the methylene protons. The carbon atom of derivatives by using a one-pot reaction of diverse π ac-
this methylene group resonated in the 13C NMR at ceptors and anhydrides with 2-aminobenzylamine. In
δ = 40.33 ppm. The mass spectrum exhibits the molec- all cases the reaction of two components proceeded
ular ion peak at m/z = 284. Moreover, the structure rapidly to afford the corresponding desired products
of 28 was confirmed by an X-ray diffraction study in excellent yields. The reaction conditions are mild,
(Fig. 2).
the work-up is simple, and the steps are automation-
The quinazoline derivative 30 was formed when friendly. The structures of two selected examples (26
one equivalent of 1 was fused with one equivalent and 28) were elucidated by single X-ray diffraction
of the anhydride 29; its structure was fully supported analysis. The mechanism of formation of the obtained
by elemental analysis and its mass spectrum, which products 5, 6, 36, and 37 has been rationalized.
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
Table 1. Crystallographic data for compounds 26 and 28.
919
(400 MHz, [D6]DMSO): δ = 4.33 (d, 2H, CH2, J =
5.25 Hz), 7.41 – 7.56 (m, 4H), 7.96 – 7.98 (dd, 1H, J = 1.72,
7.54 Hz), 7.66 – 7.73 (m, 2H), 8.12 – 8.14 (dd, 1H, J =
1.70, 7.66 Hz), 8.38 (t, 1H, NH, J = 5.10 Hz). – 13CNMR
(100 MHz, [D6]DMSO): δ = 44.80 ( CH2), 103.41 (C),
106.04 (C), 124.61 (CH), 125.74 (CH), 127.14 (CH), 129.06
(CH), 129.11 (C), 129.15 (CH), 130.85 (CH), 131.55 (CH),
132.03 (CH), 135.11 (C), 145.44 (C), 149.41 (C), 151.14
(C=N), 174.59 (CO). – MS (EI, 70 eV): m/z(%) = 297 (5),
296 (30), 294 (100) [M]+, 293 (16), 268 (5), 260 (10), 259
(16) [M−HCl]+, 251 (4), 233 (2), 232 (8), 231 (9), 229 (18),
217 (4), 203 (10), 190 (2), 176 (5), 165 (4), 156 (4), 134 (2),
128 (4), 115 (10), 102 (16), 89 (12), 77 (4). – C17H11ClN2O
(294.06): calcd. C 69.28, H 3.76, N 9.50; found C 69.17, H
3.75, N 9.43.
Compound
26
28
Formula
C15H14N2O
C15H14N2O
Mr
238.28
278.33
Habit
colorless tablet colorless tablet
Crystal size, mm3
Crystal system
Space group
Temperature, ◦C
0.35×0.3×0.2 0.3×0.15×0.1
monoclinic
P21/n
−133
monoclinic
P21/n
−173
˚
a, A
6.1268(2)
10.5576(3)
18.0859(5)
90.357(3)
1169.85
4
5.2041(6)
17.6877(16)
14.1232(16)
90.03(2)
1300.0
4
˚
b, A
˚
c, A
β, deg
3
˚
V, A
Z
Dcalcd., Mg m−3
µ(MoKα ), mm−1
F(000), e
1.35
1.45
0.1
0.1
504
592
Reaction of 2-aminobenzylamine (1) with
1,1,2,2-tetracyanoethylene (5)
2θmax, deg
60
56.6
Refl. measured / unique / Rint 41055 / 3412 / 30329 / 3215 /
0.028
163
0.041
0.107
1.02
0.044
200
0.041
0.106
1.06
To 128 mg (1.0 mmol) of 5 in anhydrous ethyl acetate
(20 mL), 122 mg (1.0 mmol) of 1 in 10 mL of anhydrous
ethyl acetate was added with stirring within 1/2 h. The mix-
ture was stirred for 7 h at room temperature, during which
time a crystalline colorless product separated. The resulting
solid material was filtered, and the precipitate was washed
with ethyl acetate, dried and recrystallized from ethanol to
give the quinazoline derivative 6. The filtrate was concen-
trated to dryness, and the residue was subjected to column
chromatography using CH2Cl2 as an eluent to give a red
zone which was removed and extracted to give the quin-
azoline derivative 7.
Ref. parameters
R[F > 4σ(F)]
wR(F2, all refls.)
S
−3
˚
∆ρmax, e A
0.35
0.31
Experimental Section
General. All reagents were purchased from Acros and
Aldrich companies and were used without further purifica-
tion. The melting points were measured in capillary tubes
without corrections using a Bu¨chi 530 melting point appa-
ratus. The NMR spectra were recorded on a Bruker AM
400 MHz spectrometer with TMS as internal standard; the
2-(3,4-Dihydroquinazolin-2(1H)-ylidene)malononitrile (6)
Colorless powder (yield: 147 mg, 75%), m. p. > 240 ◦C.
coupling constants are given in Hz. The mass spectra (EI) – IR (film): ν = 3272, 3218 (NH), 3168, 3059, 2944, 2870
were performed using a Finnigan MAT 8430 spectrometer. (CH), 2207, 2175 (CN), 1596, 1552 (C=C) cm−1. – 1H
IR spectra were run from KBr discs using a Bruker Tensor 27 NMR (400 MHz, [D6]DMSO): δ = 4.38 (d, 2H, CH2, J =
instrument. Chromatography columns were prepared from 1.00 Hz), 7.04 – 7.09 (m, 1H), 7.15 (d, 1H, J = 7.41 Hz),
Merck silica gel 230 – 240 mesh.
7.19 – 7.25 (m, 2H), 8.32 (s, 1H, NH), 10.26 (s, 1H, NH). –
13CNMR (100 MHz, [D6]DMSO): δ = 41.12 ( CH2), 115.95
(CH), 117.62 (C), 119.16 (C), 124.08 (CH), 125.91 (CH),
128.16 (CH), 133.71 (C), 158.05 (C). – MS (EI, 70 eV):
m/z(%) = 197 (7) [M+1]+, 196 (75) [M]+, 195 (100)
[M−1]+, 168 (22) [M−HCN]+, 141 (10), 129 (7), 116 (4),
104 (6), 97 (4), 89 (2), 77 (8). – C11H8N4 (196.07): calcd. C
67.34, H 4.11, N 28.55; found C 67.25, H 4.13, N 28.49.
Synthesis of 6-chloro-7,8-dihydro-5H-benzo[e]naphtho[2,1-
b][1,4]diazepin-5-one (3)
To 227 mg (1.0 mmol) of 2 in anhydrous ethyl acetate
(10 mL) at room temperature was added dropwise a solution
of 1 (122 mg, 1.0 mmol) in anhydrous ethyl acetate (10 mL).
The color of the reaction mixture changed to deep red. The
mixture was stirred at room temperature for 9 h. A red precip-
itate separated. The resulting precipitate was filtered, washed
with ethyl acetate, dried and recrystallized from EtOH to give
the diazepine derivative 3.
1,4-Dihydroquinazolin-2-carbonitrile (7)
Deep-red powder (yield: 35 mg, 22%), m. p.
121 – 123 ◦C. – IR (film): ν = 3278 (NH), 3135, 3059,
Red powder (yield: 259 mg, 88%), m. p. > 240 ◦C. 2976, 2864 (CH), 2180 (CN), 1695, 1619, 1575 (C=N,
– IR (film): ν = 3284 (NH), 3066, 2923, 2853 (CH), C=C) cm−1. – 1H NMR (400 MHz, CDCl3): δ = 4.73
1630 (CO), 1590 (C=N), 1539 (C=C) cm−1. – 1H NMR (s, 2H, CH2), 6.91 (d, 1H, J = 7.41 Hz), 7.09 – 7.13 (m,
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
2H), 7.20 – 7.24 (m, 1H), 7.31 – 7.37 (m, 1H). – 13C NMR 2871 (CH), 2185, 2133 (CN), 1598, 1566 (C=C) cm−1. –
(100 MHz, CDCl3): δ = 42.02 ( CH2), 108.83 (C), 126.01 1H NMR (400 MHz, [D6]DMSO): δ = 4.76 (s, 2H, CH2),
(CH), 126.41 (CH), 128.12 (C), 128.55 (CH), 128.59 (CH), 6.90 (d, 2H, J = 8.81 Hz), 7.20 – 7.27 (m, 3H), 7.32 – 7.38
129.68 (CH), 147.49 (C). – MS (EI, 70 eV): m/z(%) = 158 (m, 1H), 7.60 (d, 2H, J = 8.81 Hz), 10.12 (br s, 1H, NH),
(5) [M+1]+, 157 (40) [M]+, 156 (100) [M−1]+, 129 (22) 11.51 (br s, 1H, NH). – 13CNMR (100 MHz, [D6]DMSO):
[M−HCN]+, 102 (6), 77 (10). – C9H7N3 (157.06): calcd. δ = 41.62 ( CH2), 112.14 (C), 116.84 (CH), 117.38 (2CH),
C 68.78, H 4.49, N 26.74; found C 68.61, H 4.44, N 26.60.
118.55 (C), 122.93 (C), 126.07 (CH), 126.46 (CH), 128.63
(CH), 128.85 (2CH), 132.61 (C), 149.92 (C), 156.48 (C). –
MS (EI, 70 eV): m/z(%) = 273 (15) [M+1]+, 272 (100)
[M]+, 243 (30) [M−HCN]+, 215 (10), 205 (6), 178 (10),
164 (2), 151 (5), 141 (10), 129 (12), 122 (10), 114 (5),
104 (25), 95 (3), 85 (3), 76 (20). – C17H12N4 (272.11):
calcd. C 74.98, H 4.44, N 20.58; found C 74.87, H 4.41, N
20.47.
Synthesis of 6,7-dichloro-8-oxo-10,11-dihydro-8H-
dibenzo[b,e][1,4]diazepine-9-carbonitrile (9)
To 227 mg (1.0 mmol) of 8 in anhydrous ethyl acetate
(15 mL) was added dropwise a solution of compound 1
(122 mg, 1.0 mmol) in anhydrous ethyl acetate (10 mL) at
room temperature. The color of the reaction mixture changed
to deep red. The mixture was stirred at room temperature
for 4 h. A red precipitate separated, which was filtered and
washed with ethyl acetate, dried and recrystallized from
EtOH to give the diazepine derivative 9.
Reactions of 2-aminobenzylamine (1) with
1,4-naphthoquinone (16) and/or 1,4-benzoquinone (18)
In a typical experiment, reactant 1 (122 mg, 1.0 mmol)
was added dropwise to a well-stirred solution of 1,4-
naphthoquinone (16) (158 mg, 1 mmol) and/or 1,4-
benzoquinone (18) (108 mg, 1.0 mmol) in anhydrous
ethylacetate (15 mL) at room temperature. The color of the
parent quinone disappeared, and the solution turned brown.
The solution was heated under reflux conditions for 3 – 5 h.
The progress of the reaction was monitored via TLC. The
volume of the solution was reduced to half under reduced
pressure. A brown precipitate appeared which was filtered,
dried at room temperature and recrystallized from EtOH to
obtain the desired products 17 and 19.
Deep-red powder (yield: 264 mg, 87%), m. p.
201 – 204 ◦C. – IR (film): ν = 3296 (NH), 3015, 2921,
2875 (CH), 2209 (CN), 1663 (CO), 1559 (C=C) cm−1
.
–
1H NMR (400 MHz, [D6]DMSO): δ = 4.37 (d, 2H,
J = 5.27 Hz, CH2), 7.34 – 7.39 (m, 1H), 7.45 – 7.49 (m, 1H),
7.59 (d, 2H, J = 2.96 Hz), 9.85 (t, 1H, NH, J = 5.16 Hz). –
13CNMR (100 MHz, [D6]DMSO): δ = 45.24 ( CH2), 79.75
(C), 114.79 (C), 127.59 (CH), 128.94 (CH), 129.57 (CH),
130.22 (C), 134.57 (C), 131.46 (CH), 140.11 (C), 144.51
(C), 147.35 (C), 155.60 (C=N), 172.15 (CO). – MS (EI,
70 eV): m/z(%) = 307 (30) [M+4]+, 305 (75) [M+2]+,
303 (100) [M]+, 289 (35), 277/275 (35/55) [M−HCN]+,
269 (20), 255 (10), 240 (35) [M−(HCN+HCl)]+, 213
(10), 204 (10) [M−(HCN+2HCl)]+, 179 (10), 177 (12),
163 (4), 153 (6), 137 (8), 104 (6), 77 (8). – C14H7Cl2N3O
(303.00): calcd. C 55.29, H 2.32, N 13.82; found C 55.18, H
2.34, N 13.70.
2-((2-Aminobenzyl)amino)naphthalene-1,4-dione (17)
Deep-brown powder (yield: 220 mg, 79%), m. p.
132 – 134 ◦C. – IR (film): ν = 3425, 3393, 3223 ( NH2,NH),
3074, 3028, 2959, 2827 (CH), 1671, 1601 (CO), 1568 (C=C)
cm−1. – 1H NMR (400 MHz, [D6]DMSO): δ = 4.22 (d,
2H, CH2, J = 6.03 Hz), 5.08 (br s, 2H, NH2), 6.50 (t, 1H,
J = 6.46 Hz), 6.61 – 6.64 (dd, 1H, J = 1.16, 8.52 Hz), 7.22
(s, 1H), 6.94 – 6.98 (m, 2H), 7.63 (t, 1H, J = 7.47 Hz), 7.73
(t, 1H, J = 7.51 Hz), 8.04 (t, 2H, J = 5.60 Hz), 8.13 (t, 1H,
Synthesis of 2-(4-(3,4-dihydroquinazolin-2(1H)-
ylidene)cyclohexa-2,5-dien-1-ylidene)malononitrile (12)
To 204 mg (1.0 mmol) of 11 in anhydrous ethyl ac- NH, J = 6.12 Hz). – 13CNMR (100 MHz, [D6]DMSO):
etate (30 mL) was added dropwise a solution of 1 (122 mg, δ = 41.74 ( CH2), 115.67 (CH), 119.01 (C), 122.82 (C),
1.0 mmol) in anhydrous ethyl acetate (10 mL) at room 125.37 (C), 126.58 (CH), 127.02 (CH), 127.11 (CH), 128.00
temperature. The color of the reaction mixture changed to (C), 128.46 (CH), 130.74 (CH), 131.66 (CH), 133.12 (CH),
green. The mixture was stirred at room temperature for 3 h. 142.16 (C), 151.10 (C), 172.54 (CO), 182.53 (CO). –
A yellowish-green precipitate separated, which was filtered MS (EI, 70 eV): m/z(%) = 280 (4) [M+2]+, 279 (16)
and washed with ethyl acetate, dried and recrystallized from [M+1]+, 278 (54) [M]+, 261 (6) [M−NH3]+, 185 (12),
DMF to give the quinazoline derivative 12.
172 (32), 156 (6), 121 (10), 106 (68), 93 (5), 76 (10). –
Yellowish-green powder (yield: 261 mg, 96%), m. p. > C17H14N2O2 (278.11): calcd. C 73.37, H 5.07, N 10.07;
240 ◦C. – IR (film): ν = 3271, 3245 (NH), 3155, 3025, 2937, found C 73.19, H 5.03, N 9.93.
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2,5-Bis((2-aminobenzyl)amino)cyclohexa-2,5-
Synthesis of 2,5-bis((2-aminobenzyl)amino)-3,6-
diene-1,4-dione (19)
dichlorocyclohexa-2,5-diene-1,4-dione (24)
Brown powder (yield: 327 mg, 94%), m. p. 219 – 222 ◦C.
– IR (film): ν = 3429, 3403, 3352, 3329 ( NH2,NH), 3074,
3028, 2917, 2873 (CH), 1629 (CO), 1583 (C=C) cm−1. –
1H NMR (400 MHz, [D6]DMSO): δ = 4.20 (d, 4H, 2CH2,
J = 6.24 Hz), 5.14 (s, 4H, NH2), 5.19 (s, 2H), 6.50 (t,
2H, J = 6.46 Hz), 6.61 – 6.64 (dd, 2H, J = 1.16, 8.52 Hz),
6.94 – 6.98 (m, 4H), 8.15 (t, 2H, 2NH, J = 6.20 Hz). –
13CNMR (100 MHz, [D6]DMSO): δ = 42.46 ( 2CH2), 93.06
(2CH), 114.94 (2CH), 115.74 (2CH), 119.18 (2C), 128.00
(2CH), 128.46 (2CH), 146.16 (2C), 151.10 (2C), 177.53
(2CO). – MS (EI, 70 eV): m/z(%) = 350 (2) [M+2]+, 349
(10) [M+1]+, 348 (40) [M]+, 331 (6) [M−NH3]+, 314
(4), 295 (5), 282 (2), 242 (48), 225 (30), 198 (5), 181 (2),
169 (5), 121 (5), 106 (100), 93 (5), 77 (12). – C20H20N4O2
(348.16): calcd. C 68.95, H 5.79, N 16.08; found C 68.79, H
5.71, N 15.89.
A solution of compound 1 (122 mg, 1.0 mmol) in anhy-
drous ethyl acetate (10 mL) was added to a magnetically
stirred solution of 2,3,5,6-tetrachloro-1,4-benzoquinone (23)
(246 mg, 1.0 mmol) in anhydrous ethyl acetate (20 mL). The
yellow color of the solution changed to deep green and then
to yellowish green. The reaction mixture was stirred at room
temperature for 5 h. After completion of the reaction (fol-
lowed by TLC), the formed precipitate was collected by fil-
tration, washed and recrystallized from EtOH to afford the
product 24.
Pale-brown powder (yield: 408 mg, 98%), m. p.
164 – 167 ◦C. – IR (film): ν = 3421, 3349, 3326 ( NH2,NH),
3025, 2996, 2921, 2849 (CH), 1638 (CO), 1564 (C=C)
cm−1. – 1H NMR (400 MHz, [D6]DMSO): δ = 4.80 (s,
4H, 2CH2), 5.11 (br s, 4H, 2NH2), 6.50 – 6.59 (m, 2H),
6.64 – 6.69 (m, 1H), 6.70 – 6.72 (m, 1H), 6.86 – 6.90 (m,
1H), 6.95 – 6.99 (m, 1H), 7.03 – 7.07 (m, 1H), 7.15 – 7.17
(dd, 1H, J = 1.20, 7.49 Hz), 8.18 (br s, 2H, 2 NH). –
13CNMR (100 MHz, [D6]DMSO): δ = 39.49 ( CH2),
114.90 (C), 115.62 (CH), 116.05 (CH), 116.18 (CH),
117.28 (CH), 122.06 (C), 121.37 (C), 126.91 (C), 127.30
(CH), 127.87 (CH), 129.39 (CH), 130.52 (CH), 144.43 (C),
146.95 (C). – MS (EI, 70 eV): m/z(%) = 420/418/416
(2/4/6) [M4+/M2+/M+], 380 (4) [M−HCl]+, 362 (2)
[M−(HCl+H2O)]+, 346 (2), 313/311/309 (10/16/12),
277/275 (5/8), 259 (7), 208 (6), 179 (3), 171 (4), 143 (3), 131
(4), 118 (7), 106 (100), 93 (5), 77 (12). – C20H18Cl2N4O2
(416.08): calcd. C 57.57, H 4.35, N 13.43; found C 57.47, H
4.33, N 13.35.
Synthesis of dimethyl 2,3,4,5-tetrahydro-1H-
benzo[e][1,4]diazepine-2,3-dicarboxylate (21)/methyl
2-(2-methoxy-2-oxoethyl)-1,2,3,4-tetrahydroquinazoline-2-
carboxylate (22)
Into a 250 mL two-necked round bottom flask contain-
ing a solution of 20 (142 mg, 1.0 mmol) in absolute CHCl3
(10 mL), a solution of 1 (122 mg, 1.0 mmol) in absolute
CHCl3 (10 mL) was added dropwise with stirring. The mix-
ture was stirred at room temperature for 1 h, and at re-
flux for 3 h monitored by TLC. The solvent was evapo-
rated under vacuum, and the residue was purified by dis-
solving in CH2Cl2 (5 mL) and then subjected to prepara-
tive plate chromatography (silica gel, diethyl ether). The ob-
tained products 21 and/or 22 were detected by spectral ana-
lyses.
Colorless oil (yield: 214 mg, 81%). – IR (film): ν =
3362 (NH), 3008, 2953, 2894 (CH), 1729 (CO), 1609, 1592
(C=C) cm−1. – 1H NMR (400 MHz, CDCl3): δ = 2.60
(br s, 1H, NH), 2.85 (d, 1H, J = 15.63 Hz, -CH–CO2CH3),
3.05 (d, 1H, J = 15.63 Hz, -CH–CO2CH3), 3.70 (s, 3H,
−CH3), 3.94 (d, 2H, J = 4.35 Hz, −CH2), 3.76 (s, 3H,
−CH3), 4.84 (br s, 1H, 1NH), 6.60 – 6.57 (dd, 1H, J = 0.92,
7.97 Hz), 6.72 – 6.67 (ddd, 1H, J = 1.14 Hz), 6.89 – 6.86 (dd,
1H, J = 1.02, 7.50 Hz), 7.00 (t, 1H, J = 7.00 Hz). – 13C
NMR (100 MHz, CDCl3): δ = 42.48 ( CH2), 43.24 ( CH2),
General procedures for the reaction of 1 with anhydrides
25, 27, 29, and 31
In a fusion tube provided with a condenser, a mixture of
compound 1 (122 mg, 1.0 mmol) and 1.0 mmol of the anhy-
dride (either 25, 27, 29 or 31) was heated in an oil bath at
200 ◦C for 5 min. Then the mixture was cooled to room tem-
perature and poured into 20 mL Et2O. The obtained solids
were collected and recystallized from EtOH or DMF to give
the products 26, 28, 30 and 32.
1,4,4a,12a-Tetrahydroisoindolo[1,2-b]quinazolin-12(10H)-
one (26)
Colorless crystals (yield: 226 mg, 95%), m. p.
51.93 ( CH3), 52.92 ( CH3), 70.63 (C), 115.18 (CH), 118.47 154 – 156 ◦C. – IR (film): ν = 3039, 2944, 2898 (CH),
(CH), 119.93 (C), 125.83 (CH), 127.38 (CH), 141.10 (C), 1730 (CO), 1641 (C=N), 1599, 1578 (C=C) cm−1. –
170.22 (CO), 172.31 (CO). – MS (EI, 70 eV): m/z(%) = 265 1H NMR (400 MHz, CDCl3): δ = 2.24 – 2.30 (m, 1H),
(4) [M+1]+, 264 (18) [M]+, 232 (7), 206 (14), 205 (96), 2.34 – 2.40 (m, 1H), 2.61 – 2.69 (m, 2H), 3.01 – 3.06 (m,
199 (6), 191 (18), 190 (62), 173 (10), 157 (38), 145 (10), 130 1H), 3.32 – 3.38 (m, 1H), 4.79 (s, 2H, CH2), 5.90 – 5.93 (m,
(40), 129 (100), 106 (46), 77 (20).
2H), 7.00 – 7.03 (m, 1H), 7.10 – 7.14 (m, 1H), 7.21 – 7.24
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K. M. El-Shaieb – P. G. Jones · The Chemical and Structural Properties of 2-Aminobenzylamine Derivatives
(m, 2H). – 13CNMR (100 MHz, CDCl3): δ = 23.25 (C – C15H6Cl4N2O (369.92): calcd. C 48.43, H 1.63, N 7.53;
H2), 25.27 (C H2), 37.36 (CH), 38.66 (CH), 41.55 ( CH2), found C 48.29, H 1.60, N 7.42.
126.09 (CH), 126.40 (CH), 126.42 (CH), 127.73 (CH),
Dibenzo[3,4:5,6]azepino[2,1-b]quinazolin-9(11H)-one (32)
128.06 (CH), 128.75 (CH), 140.39 (C), 160.73 (C=N),
178.36 (CO). – MS (EI, 70 eV): m/z(%) = 240 (3) [M+2]+,
239 (12) [M+1]+, 238 (100) [M]+, 233 (2), 223 (10), 209
(25), 195 (8), 183 (18), 168 (6), 155 (5), 144 (6), 132 (12),
116 (3), 104 (12), 97 (4), 91 (6), 76 (14). – C15H14N2O
(238.11): calcd. C 75.61, H 5.92, N 11.76; found C 75.50, H
5.90, N 11.67.
Colorless powder (yield: 214 mg, 69%), m. p. 88 – 91 ◦C.
– IR (film): ν = 3059, 2929, 2872 (CH), 1709 (CO), 1596
(C=N), 1540 (C=C) cm−1. – 1H NMR (400 MHz, CDCl3):
δ = 4.14 (s, 2H, CH2), 6.50 – 6.55 (m, 3H), 6.57 – 6.85 (m,
1H), 6.99 – 7.18 (m, 3H), 7.28 – 7.37 (m, 3H), 7.46 – 7.51 (m,
1H), 7.62 – 7.68 (m, 1H). – 13CNMR (100 MHz, CDCl3):
δ = 40.78 ( CH2), 116.18 (CH), 118.42 (CH), 127.10 (CH),
127.71 (CH), 127.83 (CH), 128.96 (CH), 129.89 (CH),
130.00 (CH), 130.19 (CH), 130.67 (CH), 134.65 (C), 139.48
(C), 175.11 (CO). – MS (EI, 70 eV): m/z(%) = 312 (2)
[M+2]+, 311 (8) [M+1]+, 310 (26) [M]+, 309 (15) (M–
1]+, 282 (30), 281 (65), 254 (10), 223 (4), 206 (4), 197 (8),
181 (18), 152 (22), 144 (10), 121 (60), 106 (30), 76 (12). –
C21H14N2O (310.11): calcd. C 81.27, H 4.55, N 9.03; found
C 81.12, H 4.51, N 8.90.
Benzo[4,5]isoquinolino[1,2-b]quinazolin-7(9H)-one (28)
Orange crystals (yield: 210 mg, 74%), m. p. 211 – 215 ◦C.
– IR (film): ν = 3064, 2967 (CH), 1737, 1694 (CO), 1623
(C=N), 1588, 1560 (C=C) cm−1. – 1H NMR (400 MHz,
[D6]DMSO): δ = 5.06 (s, 2H, CH2), 6.46 (t, 1H, J =
7.60 Hz), 6.69 (d, 1H, J = 7.47 Hz), 6.96 – 7.02 (m, 1H),
7.18 – 7.28 (m, 1H), 7.68 – 7.91 (m, 3H), 8.36 – 8.51 (m,
3H). – 13CNMR (100 MHz, [D6]DMSO): δ = 40.33 ( CH2),
114.33 (CH), 115.98 (CH), 118.84 (C), 119.71 (C), 121.68
(C), 125.76 (CH), 126.60 (CH), 127.15 (CH), 127.21 (CH),
127.87 (CH), 128.28 (C), 130.95 (CH), 132.38 (CH), 134.45
(CH), 135.30 (C), 146.14 (C), 160.73 (C=N), 171.16 (CO).
– MS (EI, 70 eV): m/z(%) = 286 (3) [M+2]+, 285 (14)
[M+1]+, 284 (65) [M]+, 283 (100), 255 (12), 227 (5), 198
(4), 180 (2), 152 (8), 142 (6), 127 (10), 114 (2), 99 (2), 76
(5). – C19H12N2O (284.09): calcd. C 80.27, H 4.25, N 9.85;
found C 80.21, H 4.26, N 9.78.
X-Ray structure determinations
Numerical details are presented in Table 1. Data col-
lection and reduction: Crystals were mounted in inert oil
on glass fibers and transferred to the cold gas stream of
an Oxford Diffraction Xcalibur E diffractometer. Measure-
ments were performed using monochromated MoKα radia-
˚
tion (λ = 0.71073 A). Absorption corrections were applied
for 28 using the multi-scan method. Structure refinement:
The structures were refined anisotropically against F2 (pro-
gram SHELXL-97) [19]. Hydrogen atoms were included us-
ing a riding model. Compound 28 was refined as a non-
merohedral twin (by 180◦ rotation about the a axis).
CCDC 922329 (26) and 922330 (28) contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data request/
cif.
1,2,3,4-Tetrachloroisoindolo[1,2-b]quinazolin-
12(10H)-one (30)
Yellow powder (yield: 336 mg, 91%), m. p. 159 – 161 ◦C.
– IR (film): ν = 3054, 2916 (CH), 1722 (CO), 1633 (C=N),
1601 (C=C) cm−1. – 1H NMR (400 MHz, [D6]DMSO):
δ = 4.37 (s, 2H, CH2), 6.27 – 6.29 (dd, 2H, J = 1.18,
7.96 Hz), 7.58 – 7.60 (dd, 2H, J = 1.57, 7.60 Hz). –
13CNMR (100 MHz, [D6]DMSO): δ = 38.82 ( CH2), 116.39
(CH), 118.31 (CH), 119.75 (C), 126.83 (C), 127.92 (C),
128.67 (C), 128.98 (C), 129.21 (C), 129.50 (C), 130.25 (CH),
133.27 (CH), 139.07 (C), 146.31 (C), 163.54 (C). – MS (EI,
Acknowledgement
K. M. El-Shaieb gratefully acknowledges the financial
70 eV): m/z(%) = 374 (15), 372 (52), 370 (100), 368 (68) support of the German Research foundation (DFG). Profes-
[M]+, 336 (8), 308 (6), 299 (5), 271 (6), 236 (6), 209 (3), sor H. Hopf is thanked for his support and helpful discus-
186 (6), 172 (2), 153 (5), 135 (3), 119 (4), 102 (5), 76 (4). sions.
[1] N. P. Abida, R. Arpana, I. Mohd, Intern. J. Pharm. &
Biol. Arch. 2011, 1651 – 1657.
[4] P. M. S. Bedi, V. Kumar, M. P. Mahajan, Bioorg. Med.
Chem. Lett. 2004, 5211 – 5213.
[2] B. Kaur, R. Kaur, Arkivoc 2007, xiii, 315 – 323.
[3] J. Kunes, J. Bazant, M. Pour, K. Waisser, M. Slosarek,
J. Janota, IL Farmaco 2000, 725 – 729.
[5] D. J. Brown, The Chemistry of Heterocyclic Com-
pounds; J. Wiley & Sons: New York, 1996.
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