Metal-free regioselective construction of diazabenzo[e]acephenanthrylene-1,2-dicarboxylates via a phosphine-mediated cycloadditon

Article abstract of DOI:10.1016/j.tet.2017.06.010

A number of new diazabenzo[e]acephenanthrylene-1,2-dicarboxylate derivatives have been prepared regiospecifically in moderate to good yields from the triphenylphosphine-mediated cyclocondensation reaction of dialkyl acetylenedicarboxylates with 1-(4-aryl)-2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)ethanones, derived from reaction of ninhydrin, o-phenylenediamine, and 1-aryl-2-(triphenylphosphoranylidene)ethanones.

Full text of DOI:10.1016/j.tet.2017.06.010

Accepted Manuscript
Metal-free regioselective construction of diazabenzo[e]acephenanthrylene-1,2-
dicarboxylates via a phosphine-mediated cycloadditon
Abdolali Alizadeh, Reza Mohammadi, Fahimeh Bayat, Long-Guan Zhu
PII:
S0040-4020(17)30629-4
10.1016/j.tet.2017.06.010
TET 28775
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 March 2017
Revised Date: 25 May 2017
Accepted Date: 5 June 2017
Please cite this article as: Alizadeh A, Mohammadi R, Bayat F, Zhu L-G, Metal-free regioselective
construction of diazabenzo[e]acephenanthrylene-1,2-dicarboxylates via a phosphine-mediated
cycloadditon, Tetrahedron (2017), doi: 10.1016/j.tet.2017.06.010.
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ACCEPTED MANUSCRIPT
Leave this area blank for abstract info.
Metal-Free Regioselective Construction of
Diazabenzo[e]acephenanthrylene-1,2-
dicarboxylates via a Phosphine-Mediated
Cycloadditon
Abdolali Alizadeh,a,* Reza Mohammadi,a Fahimeh Bayat,b Long-Guan Zhuc
aDepartment of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
bFaculty of Basic Science, Payame Noor University, Arak Branch, Arak, Iran
cDepartment of Chemistry, Zhejiang University, Hangzhou 310027 P.R. of China
1

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Metal-Free Regioselective Construction of
Diazabenzo[e]acephenanthrylene-1,2-dicarboxylates via a
Phosphine-Mediated Cycloadditon
Abdolali Alizadeh,a,* Reza Mohammadi,a Fahimeh Bayat,b Long-Guan Zhuc
aDepartment of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
bFaculty of Basic Science, Payame Noor University, Arak Branch, Arak, Iran
cDepartment of Chemistry, Zhejiang University, Hangzhou 310027 P.R. of China
Abstract—A number of new diazabenzo[e]acephenanthrylene-1,2-dicarboxylate derivatives
have been prepared regiospecifically in moderate to good yields from the triphenylphosphine-
mediated cyclocondensation reaction of dialkyl acetylenedicarboxylates with 1-(4-aryl)-2-(11H-
indeno[1,2-b]quinoxalin-11-ylidene)ethanones, derived from reaction of ninhydrin, o-
phenylenediamine, and 1-aryl-2-(triphenylphosphoranylidene)ethanones.
Keywords: Ninhydrin, o-Phenylenediamine, 1-Aryl-2-(triphenylphosphoranylidene)ethanone, 11H-Indeno[1,2-
b]quinoxalin-11-one, Dialkyl acetylenedicarboxylate Diazabenzo[e]acephenanthrylene-1,2-dicarboxylate,
Polyheterocycle, Cycloaddition.
*Corresponding author, Tel.: +98 21 8800663; fax: +98 21 88006544; e-mail: aalizadeh@modares.ac.ir
2

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1. Introduction
The synthesis of polyheterocycles is important in the generation of complex natural compounds,
medicinal and functional materials.1 Among them, polycyclic nitrogen heterocycles are vital
scaffolds due to their prevalence in pharmaceutical active natural compounds.2 Isoindolo-
quinoxalies 13 and imidazo-quinoxaline represent interesting antineoplastic activity and potent
inhibitor of IKK-2, respectively.4 Pyrido[1,2-a]quinoxalines exhibit pH-dependent UV-visible
absorption and fluorescence characteristics.5 Another group of polycyclic quinoxalines namely,
indenoquinoxalines, are widely utilized as building block for the construction of spiro
compounds6 and organic semiconductors.7 They are also known as potent AChE inhibitor,8
antimetabolic,9 antibacterial,10 and anticancer agents 2.11 5-Thia-1,8b-diazaacenaphthylene
derivatives were known to be effective in reducing plasma lipoprotein and specially N-[1-(3-
phenylpropan-1-yl)piperidin-4-yl]-5-thia-1,8b-diazaacenaphthylen-4-carboxamide 3 decreases
non-high density lipoprotein cholesterol and triglycerides in hamsters and has potential for
preventing atherosclerosis (Figure 1).12 Therefore, the development of general protocols for the
construction of polyheterocycles is of great interest.
Figure 1. Structure of some polycyclic nitrogen heterocycles with biological activities.
Various synthetic methodologies have been developed to synthesis heterocycles. Among them
zwitterion chemistry has been regarded as one of the most interesting strategies.13 Nucleophilic
addition of phosphorus at unsaturated carbon like dialkyl acetylenedicarboxylate yields
3

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zwitterion that in reaction with dipolarophile results phosphorus or non-phosphorus containing
products. For example 2,5-dihydro-1,2-oxaphospholes were synthesized from the reaction of
triphenylphosphine, acetylenic compounds and ethyl 3-bromopyruvate.14 Also three-component
reaction of amine, diketene and dibenzoylacetylene in the presence of triphenylphosphine
yielded functionalized furamide derivatives as non-phosphorous products.15
Since polycyclic nitrogen heterocycles have widely been applied in discovery of novel bioactive
compounds,16 it promoted us to choose zwitterion resulted from triphenylphosphine and dialkyl
acetylenedicarboxylate as 1,3-dipole for reaction with 1-(4-aryl)-2-(11H-indeno[1,2-
b]quinoxalin-11-ylidene)ethanone having the chalcone structure which has been applied for the
production of spiro indenoquinoxalines by Shaabanzadeh et al.17
2. Results and Discussion
Initially we explored the preparation of 1-(4-aryl)-2-(11H-indeno[1,2-b]quinoxalin-11-
ylidene)ethanone 4 (Scheme 1) through 11H-indeno[1,2-b]quinoxalin-11-one described by
Deady et al.18 11H-Indeno[1,2-b]quinoxalin-11-one previously was used as intermediate for
construction of various compounds like spiropyrrozolidines,19 and pyrroles.20
O
Ar
O
O
O
O
H2N
H2N
PPh3
Ar
AcONa (1.5 mmol)
EtOH, r.t., 1 h
O
+
N
N
EtOH, r.t., 2 h
N
N
4
11H-indeno[1,2-b]quinoxalin-11-one
Ar: C6H5, p-BrC6H4, p-
ClC6H4, p-NO2C6H4
O
different solvents,
and bases or acids
Ph
No product
Scheme 1. Synthesis of 1-(4-aryl)-2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)ethanone 4
4

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The reaction of o-phenylenediamine and ninhydrin in EtOH at room temperature in the presence
of sodium acetate gives known 11H-indeno[1,2-b]quinoxalin-11-one.16 Addition of
acetophenone to the reaction mixture in the presence of different bases like Et3N, piperidine, and
KOH at ambient temperature or reflux conditions in different solvents did not yield the product.
Next, we screened conditions for the Wittig olefination of 11H-indeno[1,2-b]quinoxalin-11-one.
Surprisingly, in the presence of 1-aryl-2-(triphenylphosphoranylidene)ethanone, the reaction
proceeded effectively and was completed to afford the desired 1-(4-aryl)-2-(11H-indeno[1,2-
b]quinoxalin-11-ylidene)ethanone 4.
In continuation of this research, we became interested in the application of 4 as dipolarophile in
reaction with a 1,3-dipole generated from dialkyl acetylenedicarboxylate and triphenylphosphine
for manufacture of polycyclic nitrogen heterocycles. Our strategy to reach this goal is outlined in
Scheme 2. To a solution of 4a and triphenylphosphine, in DCM was added dimethyl
acetylenedicarboxylate 5a. After the work-up and chromatographic purification, a dark green
solid product was isolated in 88% yield. Compound 4a have one enone and one enimine unit, so
1
two products are possible. The H and 13C NMR spectra of the product clearly indicated the
formation of 6a.
Scheme 2. Our strategy to construction of diazabenzo[e]acephenanthrylene-1,2-dicarboxylate 6a
We went on to consider similar reactions using 4 equiv. of reactants in different solvents. The
highest yield was obtained in DCM. Finally, the reaction was also tested in the presence of
5

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catalytic amount of triphenylphosphine. Unfortunately, the yield of the product decreased
significantly.
Table 1. Optimization of the reaction conditions of 4 with dimethyl acetylenedicarboxylate in
the presence of 1 mmol triphenylphosphine
Entry
Solvent
Toluene
CHCl3
CH2Cl2
CH3CN
THF
Yields of 6a (%)
1
2
3
4
5
75
40
88
60
15
Having optimized the reaction conditions, we turned our attention to examine the scope of
reactions. The results are summarized in Table 2. It was noticeable that diisopropyl
acetylenedicarboxylate did not work in this reaction, probably due to the greater steric hindrance
of the isopropyl group. Furthermore, the use of substituted o-phenylenediamines like 4-bromo or
chloro-o-phenylenediamine did not give compound 4.
Table 2. Synthesis of diazabenzo[e]acephenanthrylene-1,2-dicarboxylates 6a-g
Entry
6a
Ar
R
CH3
Et
Yield of 6 (%)
C6H5
88
81
92
90
6b
C6H5
p-BrC6H4
p-BrC6H4
CH3
Et
6c
6d
6

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p-ClC6H4
CH3
CH3
Et
87
91
84
6e
6f
p-NO2C6H4
p-NO2C6H4
6g
1
The structures of all the products 6a−g were deduced from their IR, mass, H NMR, and 13C
NMR spectra and unambiguously confirmed by X-ray crystal structure analysis of 6e (Fig. 2).
Figure 2. ORTEP diagram for compound 6e
Although the reaction yielded only the product 6, presumably because of a [1,5]-H shift, two
tautomers were recognized in NMR spectroscopies and two signals were observed for most of
chemically different carbons and hydrogens (Scheme 3).
Scheme 3. [1,5]-H shift in 6
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In its 1H NMR spectrum of 6a four singlet signals at 3.53, 3.64, 3.71, and 3.75 ppm are related to
two methoxy groups of two isomers. The CH groups were appeared as two separate singlet
1
signals at 7.03 and 7.11 ppm. The observation of four distinct signals in the H-decoupled 13C
NMR spectrum of 6a at 51.67, 51.8, 53.22, and 53.3 ppm related to methoxy groups is in
agreement with the proposed two tautomers.
Based on these results, a plausible mechanism for the synthesis of polycyclic nitrogen
heterocycle 6 has been proposed (Scheme 4).
RO2C
Ph3P
+
CO2R
5
CO2R
Ph3P
CO2R
N
O
7
Ar
H
CO2R
CO2R
Ar
O
CO2R
CO2R
Ar
O
N
PPh3
N
N
N
9
4
8
N
keto-enol
tautomerization
CO2R
O
CO2R
OH
H
CO2R
CO2R
Ar
Ar
N
[1,5]H shift
N
N
N
6 major
10
Scheme 4. Proposed mechanism
Based on the well-recognized chemistry of trivalent phosphorus nucleophiles,14-15 it is reasonable
to assume that initial addition of triphenylphosphine to the dialkyl acetylenedicarboxylate and
subsequent attack of the resulting zwitterion 7 to the double bond of 4 yields the intermediate 8.
8

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Then 8 apparently cyclizes through the attack of nitrogen and removal of triphenylphosphine (8
to 9). Finally the product 6 is produced through a keto-enol tautomerization (9 to 10) and a [1,5]-
H shift respectively.
3. Conclusion
In conclusion, we succeeded in synthesizing novel diazabenzo[e]acephenanthrylene-1,2-
dicarboxylates,
via
triphenylphosphine-mediated
cycloaddition
of
dialkyl
acetylenedicarboxylates to 1-(4-aryl)-2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)ethanones.
Substrates for these transformations are easily accessed via the sequential three-component
reaction of ninhydrin, phenylenediamine, and 1-aryl-2-(triphenylphosphoranylidene)ethanone.
The salient features of this procedure are moderate to good yields, chemo- and regioselectivity,
metal-catalyst free and easy operation.
4. Experimental
Melting points measured on an Electrothermal 9100 apparatus. IR spectra were recorded as KBr
13
pellets on a NICOLET FT-IR 100 spectrometer. 1H NMR (500 MHz) and C NMR (125 MHz)
spectra were obtained using Bruker DRX-500 AVANCE spectrometers. NMR spectra at room
temperature were recorded in CDCl3. Chemical shifts are reported in parts per million (δ)
downfield from an internal tetramethylsilane reference. Coupling constants (J values) are
reported in Hertz (Hz), and spin multiplicities are indicated by the following symbols: bs (broad
singlet), s (singlet), d (doublet), t (triplet), m (multiplet). Elemental analyses for C, H and N
performed using a Heraeus CHN–O–Rapid analyzer. Mass spectra were recorded on a
FINNIGAN-MATT 8430 mass spectrometer operating at an ionization potential of 20 or 70 eV.
9

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4.1. General procedure for the preparation of 1-(4-aryl)-2-(11H-indeno[1,2-
b]quinoxalin-11-ylidene)ethanone 4a-d.
To a solution of ninhydrin (1 mmol) and phenylenediamine (1 mmol) in EtOH (4 mL) was added
sodium acetate (1.5 mmol), and the solution was stirred for 1 h at room temperature. Then, 1-
aryl-2-(triphenylphosphoranylidene)ethanone (1.5 mmol) was added. Upon completion (2 h) as
monitored by TLC the reaction mixture was filtered and the filtrate recrystallized in EtOH.
4.2. General procedure for the preparation of compounds 6a-g.
To a mixture of 1-(4-aryl)-2-(11H-indeno[1,2-b]quinoxalin-11-ylidene)ethanone 4 (1 mmol) and
triphenylphosphine (1 mmol) in dichloromethane (3 mL) was added a solution of dialkyl
acetylenedicarboxylates 5 (1 mmol) in dichloromethane (1 mL) at room temperature. When the
reaction was complete (3 h, TLC), the solvent was removed and the residue was purified by flash
column chromatography [silica gel, hexane–EtOAc (3:1)] to afford the pure product 6.
4.2.1. Dimethyl
3-benzoyl-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-dicarboxylate
(6a-major). Dark green powder, m.p. = 245-247 °C, 0.42 g, yield: 88% (major: 44.34%, minor:
43.66%). IR (KBr) (νmax, cm-1): 1737 (C=O), 1688 (CO2Me), 1603, 1502 (Ar) and 1233 (C-O).
Anal. Calcd. for C29H20N2O5 (476.49): C, 73.10; H, 4.23; N, 5.88%. Found: C, 73.14; H, 5.21; N,
5.87%. MS (EI, 70 eV): m/z (%) = 476 (M+, 1), 389 (6), 388 (23), 106 (19), 105 (100), 103 (7),
79 (11), 77 (9). 1H NMR (500.13 MHz, CDCl3): δH 3.64 (3H, s, OCH3), 3.71 (3H, s, OCH3), 7.11
3
3
(1H, s, CH1), 7.20 (1H, d, JHH = 8.1 Hz,CH12), 7.22 (1H, d, JHH = 8.1 Hz, CH9), 7.32 (1H, t,
3
3
3JHH = 6.8 Hz, CH11), 7.58 (1H, t, JHH = 8.2 Hz, CH10), 7.60 (1H, t, JHH = 8.2 Hz, CH5), 7.67
3
3
(1H, t, JHH = 7.7 Hz, CHpara of Ph), 7.72-7.76 (2H, m, 2CHmeta of Ph), 7.85 (1H, d, JHH = 7.5
Hz, CH4), 8.24 (2H, d, 3JHH = 8.1 Hz, 2CHortho of Ph), 8.25 (1H, t, 3JHH = 8.6 Hz, CH6), 8.33 (1H,
13
d, 3JHH = 8.6 Hz, CH7). C NMR (125.77 MHz, CDCl3): δC 51.67 (OCH3), 53.22 (OCH3), 56.8
(CH1), 101.8 (C2), 101.9 (C3a), 112.8 (CH12), 119.0 (CH4), 123.0 (CH7, CH10), 124.9 (CH11),
10

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128.4 (2CHmeta of Ph), 128.7 (CH5), 129.0 (2CHortho of Ph), 129.9 (C12a), 130.4 (CH6), 131.2
(CH9), 132.3 (CHpara of Ph), 133.5 (C12c), 133.8 (C7a), 135.6 (C3), 138.3 (Cipso of Ph), 140.6
(C8a), 146.1 (C3b), 155.1 (C7b), 164.8 (CO2Me), 168.2 (CO2Me), 194.7 (C=O).
4.2.2. Dimethyl 3-benzoyl-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-dicarboxylate
1
(6′a-minor). H NMR (500.13 MHz, CDCl3): δH 3.53 (3H, s, OCH3), 3.75 (3H, s, OCH3), 6.87
(1H, d, 3JHH = 7.7 Hz,CH12), 7.03 (1H, s, CH12c), 7.35 (1H, t, 3JHH = 7.4 Hz, CH11), 7.48 (1H, d,
3
3
3JHH = 7.4 Hz, CH9), 7.60 (1H, t, JHH = 8.2 Hz, CH5), 7.61 (1H, t, JHH = 7.5 Hz, CH10), 7.67
3
3
(1H, t, JHH = 7.7 Hz, CHpara of Ph), 7.72-7.76 (2H, m, 2CHmeta of Ph), 7.85 (1H, d, JHH = 7.5
Hz, CH4), 8.24 (2H, d, 3JHH = 8.1 Hz, 2CHortho of Ph), 8.25 (1H, t, 3JHH = 7.1 Hz, CH6), 8.30 (1H,
3
d, JHH = 8.2 Hz, CH7). 13C NMR (125.77 MHz, CDCl3): δC 51.8 (OCH3), 53.3 (OCH3), 56.8
(CH12c), 101.9 (C2), 102.2 (C3a), 113.1 (CH12), 119.0 (CH4), 124.9 (CH7, CH10), 125.0 (CH11),
128.4 (2CHmeta of Ph), 128.7 (CH5), 129.0 (2CHortho of Ph), 129.9 (C12a), 130.5 (CH6), 131.2
(CH9), 132.3 (CHpara of Ph), 133.5 (C1), 133.8 (C7a), 135.6 (C3), 138.3 (Cipso of Ph), 140.6 (C8a),
144.1 (C3b), 155.2 (C7b), 164.9 (CO2Me), 168.1 (CO2Me), 195.1 (C=O).
4.2.3.
Diethyl
3-benzoyl-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-dicarboxylate
(6b-major). Dark green powder, m.p. = 182-184 °C, 0.40 g, yield: 81% (major: 42.13%, minor:
38.87%). IR (KBr) (νmax, cm-1): 1734 (C=O), 1685 (CO2Et), 1605, 1516 (Ar) and 1229 (C-O).
Anal. Calcd. for C31H24N2O5 (504.54): C, 73.80; H, 4.79; N, 5.55%. Found: C, 73.84; H, 4.78; N,
5.57%. MS (EI, 70 eV): m/z (%) = 505 (M++1, 1), 504 (M+, 2), 432 (32), 431 (100), 403 (17),
1
359 (19), 331 (9), 329 (11), 255 (12), 254 (39), 253 (21), 105 (80), 77 (55). H NMR (500.13
MHz, CDCl3): δH 0.93 (3H, t, 3JHH = 7.5 Hz, OCH2CH3), 1.21 (3H, t, 3JHH = 7.1 Hz, OCH2CH3),
4.03-4.26 (4H, m, 2OCH2CH3), 7.02 (1H, s, CH1), 7.19 (1H, d, 3JHH = 7.9 Hz, CH12), 7.32 (1H, t,
3JHH = 7.3 Hz, CH11), 7.50 (1H, t, 3JHH = 7.0 Hz, CHpara of Ph), 7.57 (1H, t, 3JHH = 7.5 Hz, CH10),
3
3
7.66 (1H, d, JHH = 7.3 Hz, CH9), 7.75-7.77 (2H, m, CH5, CH4), 7.87 (2H, d, JHH = 8.1 Hz,
11

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3
3
2CHmeta of Ph), 8.24 (2H, d, JHH = 7.5, 2CHortho of Ph), 8.25 (1H, t, JHH = 7.6 Hz, CH6), 8.33
3
(1H, d, JHH = 8.6 Hz, CH7). 13C NMR (125.77 MHz, CDCl3): δC 14.2 (OCH2CH3), 14.6
(OCH2CH3), 57.6 (CH1), 61.6 (2OCH2CH3), 102.6 (C2), 103.0 (C3a), 113.8 (CH12), 119.5 (CH4),
123.5 (CH7), 123.6 (CH10), 125.3 (CH11), 129.2 (2CHmeta of Ph), 129.5 (2CHortho of Ph), 129.6
(CH5), 129.7 (C12a), 130.8 (CH6), 131.6 (CH9), 132.8 (CHpara of Ph), 132.9 (C12c), 134.1 (C7a),
134.3 (C3), 137.1 (Cipso of Ph), 138.6 (C8a), 144.5 (C3b), 155.1 (C7b), 163.9 (CO2Et), 168.1
(CO2Et), 193.0 (C=O).
4.2.4.
Diethyl 3-benzoyl-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-dicarboxylate
1
3
(6′b-minor). H NMR (500.13 MHz, CDCl3): δH 0.90 (3H, t, JHH = 7.5 Hz, OCH2CH3), 1.00
(3H, t, 3JHH = 7.1 Hz, OCH2CH3), 4.03-4.26 (4H, m, 2OCH2CH3), 6.86 (1H, d, 3JHH = 7.8, CH12),
7.09 (1H, s, CH12c), 7.35 (1H, t, 3JHH = 7.7 Hz, CH11), 7.50 (1H, t, 3JHH = 7.0, CHpara of Ph), 7.60
3
3
(1H, t, JHH = 7.0 Hz, CH10), 7.66 (1H, d, JHH = 7.3 Hz, CH9), 7.75-7.77 (2H, m, CH5, CH4),
7.87 (2H, d, 3JHH = 8.1 Hz, 2CHmeta of Ph), 8.24 (2H, d, 3JHH = 7.5 Hz, 2CHortho of Ph), 8.25 (1H,
3
3
13
t, JHH = 7.6 Hz, CH6), 8.29 (1H, d, JHH = 8.1 Hz, CH7). C NMR (125.77 MHz, CDCl3): δC
14.1 (OCH2CH3), 14.4 (OCH2CH3), 57.5 (CH12c), 63.0 (2OCH2CH3), 102.8 (C2), 103.4 (C3a),
113.1 (CH12), 119.5 (CH4), 123.5 (CH7), 123.7 (CH10), 125.3 (CH11), 129.2 (2CHmeta of Ph),
129.5 (2CHortho of Ph), 129.6 (CH5), 129.7 (C12a), 130.9 (CH6), 131.6 (CH9), 132.5 (C1), 132.8
(CHpara of Ph), 134.3 (C3,C7a), 135.2 (Cipso of Ph), 138.6 (C8a), 144.5 (C3b), 154.6 (C7b), 163.8
(CO2Et), 167.1 (CO2Et), 193.0 (C=O).
4.2.5.
Dimethyl
3-(4-bromobenzoyl)-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6c-major). Dark green powder, m.p. = 196-198 °C, 0.51 g, yield: 92% (major:
46.02%, minor: 45.98%). IR (KBr) (νmax, cm-1): 1739 (C=O), 1686 (CO2Me), 1603, 1501 (Ar)
and 1226 (C-O). Anal. Calcd. for C29H19BrN2O5 (555.38): C, 62.72; H, 3.45; N, 5.04%. Found:
C, 62.79; H, 3.42; N, 5.07%. MS (EI, 70 eV): m/z (%) = 555 (M+, 1), 497 (5), 495 (5), 389 (6),
12

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388 (23), 254 (5), 106 (19), 105 (100), 103 (7), 79 (11), 77 (9). 1H NMR (500.13 MHz, CDCl3):
δH 3.67 (3H, s, OCH3), 3.73 (3H, s, OCH3), 7.15 (1H, d, 3JHH = 7.7 Hz, CH12), 7.00 (1H, s, CH1),
7.24 (1H, t, 3JHH = 7.8 Hz, CH11), 7.35 (1H, t, 3JHH = 7.6 Hz, CH10), 7.50 (1H, d, 3JHH = 8.2 Hz,
CH9), 7.58-7.74 (2H, m, CH5, CH4), 7.73 (2H, d, 3JHH = 8.4 Hz, 2CH of Ar), 8.11 (2H, d, 3JHH
=
3
3
8.1 Hz, 2CH of Ar), 8.24 (1H, t, JHH = 7.1 Hz, CH6), 8.30 (1H, d, JHH = 9.9 Hz, CH7). 13C
NMR (125.77 MHz, CDCl3): δC 51.9 (OCH3), 53.3 (OCH3), 56.7 (CH1), 101.6 (C2), 101.9 (C3a),
113.2 (CH12), 118.9 (CH4), 123.2 (CH7), 123.3 (CH10), 125.1 (C3, CH11), 127.9 (C-Br), 128.7
(C12a), 129.1 (C12c), 129.9 (CH5), 130.5 (CH6), 131.1 (CH9), 132.1 (2CH of Ar), 132.5 (2CH of
Ar), 135.3 (C7a), 138.1 (Cipso of Ar), 140.4 (C8a), 145.3 (C3b), 154.8 (C7b), 164.8 (CO2Me), 168.9
(CO2Me), 193.7 (C=O).
4.2.6.
Dimethyl 3-(4-bromobenzoyl)-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6′c-minor). 1H NMR (500.13 MHz, CDCl3): δH 3.59 (3H, s, OCH3), 3.71 (3H, s,
OCH3), 6.85 (1H, d, 3JHH = 7.6 Hz, CH12), 7.08 (1H, s, CH12c), 7.22 (1H, t, 3JHH = 7.8 Hz, CH11),
7.35 (1H, t, 3JHH = 7.6 Hz, CH10), 7.50 (1H, d, 3JHH = 8.2 Hz, CH9), 7.58-7.74 (2H, m, CH5), 7.73
(2H, d, 3JHH = 8.4 Hz, 2CH of Ar), 7.83 (1H, d, 3JHH = 8.3 Hz, CH4), 8.11 (2H, d, 3JHH = 8.1 Hz,
3
3
2CH of Ar), 8.24 (1H, t, JHH = 7.1 Hz, CH6), 8.34 (1H, d, JHH = 8.1 Hz, CH7). 13C NMR
(125.77 MHz, CDCl3): δC 51.8 (OCH3), 53.4 (OCH3), 56.8 (CH12c), 102.0 (C3a), 102.1 (C2),
112.8 (CH12), 118.9 (CH4), 123.2 (CH7, CH10), 125.0 (C3, CH11), 127.9 (C-Br), 128.8 (C12a),
128.9 (C1), 130.3 (CH5), 130.6 (CH6), 131.1 (CH9), 132.4 (2CH of Ar), 132.5 (2CH of Ar), 134.4
(C7a), 140.4 (Cipso of Ar), 140.4 (C8a), 144.3 (C3b), 154.9 (C7b), 164.9 (CO2Me), 168.1 (CO2Me),
194.0 (C=O).
4.2.7.
Diethyl
3-(4-bromobenzoyl)-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6d-major). Dark green powder, m.p. = 206-208 °C, 0.52 g, yield: 90% (major:
52.72%, minor: 37.28%). IR (KBr) (νmax, cm-1): 1734 (C=O), 1683 (CO2Et), 1601, 1513 (Ar) and
13

ACCEPTED MANUSCRIPT
1223 (C-O). Anal. Calcd. for C31H23BrN2O5 (583.44): C, 63.82; H, 3.97; N, 4.80%. Found: C,
63.80; H, 3.99; N, 4.84%. MS (EI, 70 eV): m/z (%) = 583 (M++1, 1), 583 (M+, 2), 512 (25), 511
(85), 510 (29), 509 ( 84), 437 (19), 357 (18), 329 (35), 255 (33), 254 (100), 253 (55), 185 (39),
1
183 (39), 157 (32), 155(34), 76 (21), 57 (19). H NMR (500.13 MHz, CDCl3): δH 0.99 (3H, t,
3
3JHH = 7.1 Hz, OCH2CH3), 1.12 (3H, t, JHH = 7.1 Hz, OCH2CH3), 3.95-4.10 (4H, m,
3
3
2OCH2CH3), 6.75 (1H, d, JHH = 7.65 Hz,CH12), 6.90 (1H, s, CH1), 7.14 (1H, t, JHH = 7.5 Hz,
3
3
3
CH11), 7.25 (1H, t, JHH = 8.0 Hz, CH10), 7.41 (1H, d, JHH = 8.5 Hz, CH9), 7.43 (2H, d, JHH
=
8.2 Hz, 2CH of Ar), 7.64-7.72 (1H, m, CH5), 7.52 (1H, d, 3JHH = 7.8 Hz, CH4), 8.03 (2H, d, 3JHH
3
3
13
= 8.2 Hz, 2CH of Ar), 8.11 (1H, t, JHH = 8.0 Hz, CH6), 8.18 (1H, d, JHH = 8.0 Hz, CH7). C
NMR (125.77 MHz, CDCl3): δC 13.7 (OCH2CH3), 13.8 (OCH2CH3), 56.8 (CH1), 60.9
(OCH2CH3), 61.7 (OCH2CH3), 101.5 (C2), 101.6 (C3a), 113.2 (CH12), 118.7 (CH4), 122.9 (CH7,
CH10), 124.9 (CH11), 127.9 (C3, CH5), 128.7 (CH6), 128.9 (C-Br), 129.1 (C12a), 130.0 (2CH of
Ar), 130.4 (C12c), 130.5 (CH9), 131.1 (C7a), 132.3 (2CH of Ar), 138.3 (Cipso of Ar), 140.3 (C3b),
144.7 (C8a), 154.8 (C7b), 164.4 (CO2Et), 168.2 (CO2Et), 193.7 (C=O).
4.2.8.
Diethyl
3-(4-bromobenzoyl)-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-
1
3
dicarboxylate (6′d-minor). H NMR (500.13 MHz, CDCl3): δH 0.94 (3H, t, JHH = 7.1 Hz,
OCH2CH3), 1.10 (3H, t, 3JHH = 7.1 Hz, OCH2CH3), 3.95-4.10 (4H, m, 2OCH2CH3), 6.97 (1H, s,
3
3
3
CH12c), 7.04 (1H, d, JHH = 7.7 Hz,CH12), 7.12 (1H, t, JHH = 7.6 Hz, CH11), 7.25 (1H, t, JHH
=
3
8.0 Hz, CH10), 7.41 (1H, d, 3JHH = 8.5 Hz, CH9), 7.65 (2H, d , JHH = 7.1 Hz, 2CH of Ar), 7.64-
3
3
7.72 (1H, m, CH5), 7.77 (1H, d, JHH = 8.5 Hz, CH4), 8.03 (2H, d, JHH = 8.2 Hz, 2CH of Ar),
3
3
8.11 (1H, t, JHH = 8.0 Hz, CH6), 8.21 (1H, d, JHH = 8.3 Hz, CH7). 13C NMR (125.77 MHz,
CDCl3): δC 13.2 (OCH2CH3), 14.4 (OCH2CH3), 57.0 (CH12c), 60.9 (OCH2CH3), 61.7
(OCH2CH3), 102.3 (C3a), 102.2 (C2), 112.8 (CH12), 118.6 (CH4), 122.8 (CH7), 123.0 (CH10),
124.9 (CH11), 127.9 (C3, CH5), 128.7 (CH6), 128.9 (C-Br), 129.0 (C12a), 130.0 (2CH of Ar),
14

ACCEPTED MANUSCRIPT
130.4 (C1), 130.5 (CH9), 131.7 (C7a), 132.3 (2CH of Ar), 138.4 (Cipso of Ar), 140.3 (C3b), 143.8
(C8a), 154.9 (C7b), 164.4 (CO2Et), 167.6 (CO2Et), 193.9 (C=O).
4.2.9.
Dimethyl
3-(4-chlorobenzoyl)-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6e-major). Dark green powder, m.p. = 197-199 °C, 0.44 g, yield: 87% (major:
45.64%, minor: 41.36%). IR (KBr) (νmax, cm-1): 1742 (C=O), 1687 (CO2Me), 1602, 1495 (Ar)
and 1239 (C-O). Anal. Calcd. for C29H19ClN2O5 (510.93): C, 68.17; H, 3.75; N, 5.48%. Found:
C, 68.14; H, 3.71; N, 5.50%. MS (EI, 70 eV): m/z (%) = 512 (M++2, 1), 511 (M++1, 0.8), 510
(M+, 2), 454 (10), 453 (37), 452 (31), 451 (100), 254 (40), 253 (24), 139 (23), 111 (24), 41.1
1
(10). H NMR (500.13 MHz, CDCl3): δH 3.67 (3H, s, OCH3), 3.73 (3H, s, OCH3), 6.85 (1H, d,
3
3JHH = 7.6 Hz, CH12), 7.01 (1H, s, CH1), 7.23 (1H, t, JHH = 7.3 Hz, CH10), 7.31-7.37 (1H, m,
3
3
3
CH11), 7.56 (1H, d, JHH = 8.4 Hz, CH9), 7.61 (1H, d, JHH = 8.0 Hz, CH4), 7.76 (2H, d, JHH
=
8.4 Hz, 2CH of Ar), 7.76-7.85 (1H, m, CH5), 8.19 (2H, d, 3JHH = 8.2 Hz, 2CH of Ar), 8.21 (1H, t,
3JHH = 8.2 Hz, CH6), 8.31 (1H, d, 3JHH = 8.1 Hz, CH7). 13C NMR (125.77 MHz, CDCl3): δC 53.0
(OCH3), 56.8 (OCH3), 56.9 (CH1), 101.4 (C2), 101.8 (C3a), 113.3 (CH12), 119.0 (CH4), 123.1
(CH7), 123.3 (CH10), 125.2 (CH11), 128.2 (2CH of Ar), 128.8 (CH5), 129.3 (2CH of Ar), 130.0
(CH6), 130.4 (CH9), 130.7 (C12a), 131.5 (C12c), 132.4 (C7a), 135.0 (Cipso of Ar), 138.6 (C3), 140.1
(C-Br), 140.5 (C8a), 145.6 (C3b), 155.2 (C7b), 165.0 (CO2Me), 168.2 (CO2Me), 193.8 (C=O).
Crystal data for 6e C29H19ClN2O5 (CCDC 1526736): MW = 528.93, triclinic, P-1, a = 9.2425(8)
Å, b = 10.7320(11) Å, c = 14.4009(12) Å, α = 69.081(9),
β = 81.010(7), γ = 87.453(8), V =
1317.8(2) Å3, Z = 2, Dc = 1.333 mg/m3, F (000) = 548, crystal dimension 0.48×0.43×0.40 mm,
radiation, Mo Kα (λ = 0.71073Å), 3.19≤2
θ
≤25.04, intensity data were collected at 170(2) K with
/2 scanning technique, in the
a Bruker APEX area-detector diffractometer, and employing
ω
θ
range of -11≤h≤9, -12≤k≤11, -16≤l≤17; the structure was solved by a direct method, all non-
hydrogen atoms were positioned and anisotropic thermal parameters refined from 2952 observed
15

ACCEPTED MANUSCRIPT
reflections with R (into) = 0.1134 by a full-matrix least-squares technique converged to R =
0.0793 and Raw = 0.2416 [I>2sigma(I)].
4.2.10. Dimethyl 3-(4-chlorobenzoyl)-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6′e-minor). 1H NMR (500.13 MHz, CDCl3): δH 3.60 (3H, s, OCH3), 3.71 (3H, s,
OCH3), 7.10 (1H, s, CH12c), 7.16 (1H, d, 3JHH = 7.6 Hz, CH12), 7.23 (1H, t, 3JHH = 7.3 Hz, CH10),
3
3
7.31-7.37 (1H, m, CH11), 7.56 (1H, d, JHH = 8.4 Hz, CH9), 7.56 (2H, d, JHH = 8.4 Hz, 2CH of
Ar), 7.80 (1H, d, 3JHH = 8.7 Hz, CH4), 7.76-7.85 (1H, m, CH5), 8.19 (2H, d, 3JHH = 8.2 Hz, 2CH
3
3
13
of Ar), 8.21 (1H, t, JHH = 8.2 Hz, CH6), 8.27 (1H, d, JHH = 8.1 Hz, CH7). C NMR (125.77
MHz, CDCl3): δC 52.0 (OCH3), 56.4 (OCH3), 56.5 (CH12c), 101.2 (C3a), 102.1 (C2), 113.0
(CH12), 119.0 (CH4), 123.0 (CH7), 123.3 (CH10), 125.2 (CH11), 128.2 (2CH of Ar), 129.0 (CH5),
129.7 (2CH of Ar), 130.0 (CH6), 130.4 (CH9), 130.7 (C12a), 131.4 (C1), 132.5 (C7a), 134.1 (Cipso
of Ar), 138.7 (C3), 140.1 (C-Br), 140.5 (C8a), 144.6 (C3b), 155.1 (C7b), 165.1 (CO2Me), 168.3
(CO2Me), 194.1 (C=O).
4.2.11. Dimethyl
3-(4-nitrobenzoyl)-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6f-major). Dark green powder, m.p. = 198-200 °C, 0.47 g, yield: 91% (major:
51.37%, minor: 39.63%). IR (KBr) (νmax, cm-1): 1739 (C=O), 1688 (CO2Me), 1603, 1489 (Ar)
and 1227 (C-O). Anal. Calcd. for C29H19N3O7 (521.48): C, 66.79; H, 3.67; N, 8.06%. Found: C,
66.75; H, 3.70; N, 8.09%. MS (EI, 70 eV): m/z (%) = 522 (M++1, 1), 521 (M+, 3), 463 (30), 462
(98), 416 (19), 254 (47), 253 (26), 83 (21), 71 (22), 61 (21), 69 (29), 57 (53), 55 (38), 43 (100),
1
41 (32). H NMR (500.13 MHz, CDCl3): δH 3.67 (3H, s, OCH3), 3.72 (3H, s, OCH3), 6.80 (1H,
3
d, 3JHH = 7.5 Hz,CH12), 6.99 (1H, s, CH1), 7.21-7.26 (1H, m, CH11), 7.33 (1H, t, JHH = 7.5 Hz,
3
3
3
CH10), 7.60 (1H, d, JHH = 7.8 Hz, CH5), 7.85 (1H, d, JHH = 8.1 Hz, CH9), 8.05 (1H, d, JHH
=
3
3
8.1 Hz, CH4), 8.18 (2H, d, JHH = 8.3 Hz, 2CH of Ar), 8.19 (1H, t, JHH = 8.3 Hz, CH6), 8.26
3
13
(1H, d, JHH = 7.8 Hz, CH7), 8.42 (2H, s, 2CH of Ar). C NMR (125.77 MHz, CDCl3): δC 51.6
16

ACCEPTED MANUSCRIPT
(OCH3), 52.9 (OCH3), 56.2 (CH1), 100.7 (C2), 101.3 (C3a), 112.7 (CH12), 118.1 (CH4), 122.6
(CH7), 122.8 (CH10), 123.9 (2CH of Ar), 124.7 (CH11), 127.7 (C3), 128.0 (C12a), 129.3 (2CH of
Ar), 130.0 (CH5), 130.9 (CH6), 131.7 (CH9), 132.2 (C12c), 138.1 (C7a), 139.6 (Cipso of Ar), 140.4
(C8a), 144.3 (C3b), 150.2 (C-NO2), 154.3 (C7b), 164.3 (CO2Me), 168.4 (CO2Me), 192.6 (C=O).
4.2.12. Dimethyl
3-(4-nitrobenzoyl)-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6′f-minor). 1H NMR (500.13 MHz, CDCl3): δH 3.62 (3H, s, OCH3), 3.74 (3H, s,
3
OCH3), 7.07 (1H, s, CH12c), 7.11 (1H, d, JHH = 7.5 Hz,CH12), 7.21-7.26 (1H, m, CH11), 7.33
(1H, t, 3JHH = 7.5 Hz, CH10), 7.61 (1H, d, 3JHH = 7.8 Hz, CH5), 7.76 (1H, d, 3JHH = 8.1 Hz, CH9),
8.05 (1H, d, 3JHH = 8.1 Hz, CH4), 8.18 (2H, d, 3JHH = 8.3 Hz, 2CH of Ar), 8.19 (1H, t, 3JHH = 8.3
3
13
Hz, CH6), 8.31 (1H, d, JHH = 7.7 Hz, CH7), 8.42 (2H, s, 2CH of Ar). C NMR (125.77 MHz,
CDCl3): δC 51.5 (OCH3), 52.9 (OCH3), 56.3 (CH12c), 101.0 (C3a), 101.2 (C2), 112.4 (CH12),
118.1 (CH4), 122.6 (CH7), 122.8 (CH10), 123.5 (2CH of Ar), 124.7 (CH11), 127.7 (C3), 128.3
(C12a), 128.9 (2CH of Ar), 130.2 (CH5), 131.0 (CH6), 131.8 (CH9), 132.1 (C1), 138.3 (C7a), 139.6
(Cipso of Ar,C8a), 143.7 (C3b), 150.0 (C-NO2), 154.3 (C7b), 164.2 (CO2Me), 167.5 (CO2Me),
192.6 (C=O).
4.2.13. Diethyl
3-(4-nitrobenzoyl)-1H-8,12b-diazabenzo[e]acephenanthrylene-1,2-
dicarboxylate (6g-major). Dark green powder, m.p. = 161-163 °C, 0.46 g, yield: 84% (major:
51.09%, minor: 32.91%). IR (KBr) (νmax, cm-1): 1738 (C=O), 1686 (CO2Et), 1604, 1504 (Ar) and
1259 (C-O). Anal. Calcd. for C31H23N3O7 (549.54): C, 67.76; H, 4.22; N, 7.65%. Found: C,
67.75; H, 4.24; N, 7.68%. MS (EI, 70 eV): m/z (%) = 550 (M++1, 1), 549 (M+, 3), 477 (32), 476
(100), 329 (24), 254 (40), 253 (23), 73 (19), 69 (26), 57 (47), 56 (38), 55 (38), 43 (67), 42 (22),
41 (54). 1H NMR (500.13 MHz, CDCl3): δH 1.10 (3H, t, 3JHH = 7.0 Hz, OCH2CH3), 1.19 (3H, t,
3
3JHH = 6.9 Hz, OCH2CH3), 4.10-4.16 (4H, m, 2OCH2CH3), 6.79 (1H, d, JHH = 7.5 Hz,CH12),
6.98 (1H, s, CH1), 7.20-7.25 (1H, m, CH11), 7.32 (1H, t, 3JHH = 7.4 Hz, CH10), 7.58 (1H, t, 3JHH
=
17

ACCEPTED MANUSCRIPT
7.3 Hz, CH5), 7.85 (1H, d, 3JHH = 8.1 Hz, CH9), 8.07 (1H, d, 3JHH = 8.2 Hz, CH4), 8.17-8.21 (3H,
m, 2CH of Ar, CH6), 8.24 (1H, d, 3JHH = 7.7 Hz, CH7), 8.41 (2H, d, 3JHH = 8.2 Hz, 2CH of Ar).
13C NMR (125.77 MHz, CDCl3): δC 13.4 (2OCH2CH3), 56.5 (CH1), 60.8 (OCH2CH3), 62.1
(OCH2CH3), 100.9 (C2), 102.0 (C3a), 112.8 (CH12), 118.0 (CH4), 122.6 (CH7), 122.7 (CH10),
123.8 (2CH of Ar), 124.6 (CH11), 127.6 (C3), 128.1 (C12a), 129.4 (2CH of Ar), 130.1 (CH5),
130.8 (CH6), 131.7 (CH9), 132.2 (C12c), 138.0 (C7a), 139.7 (Cipso of Ar), 140.5 (C8a), 143.7 (C3b),
150.2 (C-NO2), 154.3 (C7b), 163.9 (CO2Et), 167.7 (CO2Et), 192.3 (C=O).
4.2.14. Diethyl
3-(4-nitrobenzoyl)-12cH-8,12b-diazabenzo[e]acephenanthrylene-1,2-
1
3
dicarboxylate (6′g-minor). H NMR (500.13 MHz, CDCl3): δH 1.06 (3H, t, JHH = 6.8 Hz,
OCH2CH3), 1.19 (3H, t, 3JHH = 6.9 Hz, OCH2CH3), 4.10-4.16 (4H, m, 2OCH2CH3), 7.04 (1H, s,
3
3
CH12c), 7.10 (1H, d, JHH = 7.3 Hz,CH12), 7.20-7.25 (1H, m, CH11), 7.32 (1H, t, JHH = 7.4 Hz,
CH10), 7.59 (1H, t, 3JHH = 7.3 Hz, CH5), 7.75 (1H, d, 3JHH = 8.1 Hz, CH9), 8.07 (1H, d, 3JHH = 8.2
3
Hz, CH4), 8.17-8.21 (2H, m, 2CH of Ar, CH6), 8.30 (1H, d, JHH = 7.6 Hz, CH7), 8.44 (2H, d,
3JHH = 8.2 Hz, 2CH of Ar). 13C NMR (125.77 MHz, CDCl3): δC 13.5 (OCH2CH3), 13.6
(OCH2CH3), 56.4 (CH12c), 60.8 (OCH2CH3), 62.2 (OCH2CH3), 101.4 (C3a), 102.1 (C2), 112.4
(CH12), 118.0 (CH4), 122.6 (CH7), 122.7 (CH10), 123.5 (2CH of Ar), 124.6 (CH11), 127.6 (C3),
128.4 (C12a), 129.0 (2CH of Ar), 130.3 (CH5), 130.9 (CH6), 131.8 (CH9), 132.1 (C1), 138.1 (C7a),
139.7 (Cipso of Ar,C8a), 143.2 (C3b), 150.0 (C-NO2), 154.4 (C7b), 163.9 (CO2Et), 167.0 (CO2Et),
192.9 (C=O).
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