Stereospecificity of diels-Alder reactions validated using Ab initio calculations: Synthesis of novel coumarin and phenanthridine derivatives

Article abstract of DOI:10.1080/00397910802711326

A new series of coumarin derivatives (2-5) was synthesized by reaction of phenylsulfonylacetonitrile (1) with 2-hydroxy-1-naphthaldehyde and/or salicyaldehyde. Compounds 3 and 5 were converted to the corresponding phenanthridine analogs 6 and 7, respectiv

Full text of DOI:10.1080/00397910802711326

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Stereospecificity of Diels–Alder
Reactions Validated Using Ab
Initio Calculations: Synthesis
of Novel Coumarin and
Phenanthridine Derivatives
A. El-Shafei a , A. A. Fadda b , I. I. Abdel-Gawad c
E. H. E. Youssif c
&
a Fiber and Polymer Science Program, North Carolina
State University, Raleigh, North Carolina, USA
b Department of Chemistry, Faculty of Science,
Mansoura University, Mansoura, Egypt
c Department of Chemistry, Faculty of Education,
Suez Canal University, Suez, Egypt
Version of record first published: 14 Jul 2009.
To cite this article: A. El-Shafei, A. A. Fadda, I. I. Abdel-Gawad & E. H. E.
Youssif (2009): Stereospecificity of Diels–Alder Reactions Validated Using Ab Initio
Calculations: Synthesis of Novel Coumarin and Phenanthridine Derivatives, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:16, 2954-2972
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Synthetic Communications1, 39: 2954–2972, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802711326
Stereospecificity of Diels–Alder Reactions
Validated Using Ab Initio Calculations:
Synthesis of Novel Coumarin
and Phenanthridine Derivatives
A. El-Shafei,1 A. A. Fadda,2 I. I. Abdel-Gawad,3
and E. H. E. Youssif 3
1Fiber and Polymer Science Program, North Carolina State University,
Raleigh, North Carolina, USA
2Department of Chemistry, Faculty of Science, Mansoura University,
Mansoura, Egypt
3Department of Chemistry, Faculty of Education,
Suez Canal University, Suez, Egypt
Abstract: A new series of coumarin derivatives (2–5) was synthesized by reaction
of phenylsulfonylacetonitrile (1) with 2-hydroxy-1-naphthaldehyde and=or
salicyaldehyde. Compounds 3 and 5 were converted to the corresponding phenan-
thridine analogs 6 and 7, respectively. Compound 9a was treated with different
dienophiles to furnish the endo adducts of compounds (11a–d) rather than the
exo adducts. Ab initio calculations at the Hartree-Fock (HF) level using the basis
set 6-31 G (d,p) was used to study and validate the stereospecificity of compounds
11a–d and showed clearly that the endo adducts were thermodynamically favor-
able. PM3 parameters also showed that the endo adducts are thermodynamically
and kinetically favorable. Tetrahydrobenzochromenone (11) was synthesized and
allowed to react with different aromatic diazonium salts to give the corresponding
4-arylazo derivatives (13), which were converted to the corresponding diazainde-
nophenanthrene derivatives (14) by reaction with o-diamines.
Keywords: Aromatic diazonium salt, chromen, dienophiles, 2-hydroxy-1-
naphthaldehyde, phenanthridines, phenylsulfonylacetonitrile, salicyaldehyde
Received October 22, 2008.
Address correspondence to A. El-Shafei, Fiber and Polymer Science, North
Carolina State University, 2401 Research Drive, Raleigh, NC 27695, USA. E-mail:
Ahmed_El-Shafei@ncsu.edu
2954

Novel Coumarin and Phenanthridine
INTRODUCTION
2955
This work is the continuation of a program to develop new, simple
methods for the synthesis of functionally substituted heterocycles with
anticipated biological activity. We have recently extended it to include
the investigation of the pharmacological aspects of the newly synthesized
heterocycles based on the finding that some heterocycles can achieve
activity in both the pharmacological and pesticidal areas: coumarins,
chromones, and flavones are pharmacologically important classes of
plant products. The biological importance of coumarin has resulted in
much interest in their synthesis and chemistry.[1] Some compounds of this
class, notably 3-phenylcoumarins, are reported to possess anticoagulant[2]
properties and are used as additives to food and cosmetics.[3] 3-Phenyl-
coumarins containing an azole ring have found applications as
fluorescent-brightening agents.[4]
In contrast to most other types of tumor-inhibitory compounds,
many of which exhibit toxicity, mutagenicity, and other undesirable prop-
erties, the coumarin and chromone compounds tend to show minimal side
effects. In addition, some coumarins have been recently discovered in
some natural products, many of which have been used as bactericides,[5]
fungicides,[6] anti-inflammatory agents,[7] and antitumor agents.[8]
RESULTS AND DISCUSSION
In the past few years, Fadda et al. have been exploring the synthetic
potential, scope, and limitations of activated nitriles in coumarins and
different heterocycle synthesis.[9–11] Several new approaches for the
synthesis of five- and six-membered rings and their fused heterocyclic
derivatives have been developed during this work.[12,13] In view of these
considerable efforts, our research group has been devoted to the develop-
ment of a new synthetic methodology for this class of compounds.
In the present work, we explore the synthetic potential of phenylsulfo-
nylacetonitrile (1) to form chromene derivatives via the reaction of 1 with
2-hydroxynaphthaldehyde and salicylaldehyde, respectively. Thus, com-
pound 1 reacts with 2-hydroxy-1-naphthaldehyde and=or salicylaldehyde
in the presence of a catalytic amount of triethylamine (TEA) in refluxing
ethanol to give 2-imino-3-phenylsulfonylbenzo[f]chromene (2) and 2-
imino-3-phenylsulfonylcoumarin (4) derivatives, respectively in good yields.
Mass spectral (MS) measurements and analytical data are in
complete agreement with structure 2, m=z 335 (Mþ, 10%) (cf. Schemes 1
and 2, Table 3). The infrared (IR) spectra of both 2 and 4 showed bands
at 3150 cmꢀ1 attributable to the stretching frequency of the NH group.

2956
A. El-Shafei et al.
Scheme 1. Conversion of phenylsulfonylacetonitrile to coumarin derivatives.
The 1H NMR spectra of these compounds revealed two singlet signals at
d 8.8 and 9.2 ppm due to NH (exchangeable with D2O) and C4-protons,
respectively, in addition to the aromatic protons at d (7.3–8.5) ppm.
3-Phenylsulfonyl-2H-benzo[f]-2-chromenone (3) and 3-phenylsulfonyl-
2-coumarinones (5) were synthesized via hydrolysis of 2 and 4 in a mixture
of conc. hydrochloric acid and ethanol. The mass spectrum of 3 showed the
expected molecular formula C19H12O4S m=z 336 (Mþ, 15%). The IR
Scheme 2. Synthesis of phenanthridine derivatives.

Novel Coumarin and Phenanthridine
2957
spectra of compounds 3 and 5 showed a band at 1700cmꢀ1 assigned to the
c-lactone. The 1H NMR spectrum of compound 3 revealed two doublet sig-
nals at d 8.4 (J ¼ 8.1 Hz) and 8.45 ppm (J ¼ 8.1 Hz) attributable to C9 and
C10 protons, a singlet signal at d 9.2 ppm due to the C4 proton, in addition
to the aromatic protons that appeared at d 7.55–8.25 ppm.
Moreover, the resulting coumarin derivatives have latent functional
substituents, which have the potential for further chemical transforma-
tions and give new routes for the preparation of substituted coumarin
derivatives with possible biological activity.
In addition to this evidence, the structures of compounds 3 and 5
were further confirmed by their transformation to the corresponding
phenanthridine derivatives 6 and 7 by refluxing with p-anisidine in glacial
acetic acid and freshly fused sodium acetate. Structures of compounds 6
and 7 were confirmed by both analytical and spectral data (cf. the Experi-
mental section).
The importance of coumarin and its annulated substrates is well
recognized by synthetic,[14] and biological chemists.[15] With the develop-
ment of clinically useful anticonvulsant and analgesic drugs,[16] there has
recently been remarkable interest in the synthetic manipulations of
coumarins. The synthetic utilization of the nucleophilic double bond of
coumarin is an important new field that offers great potential for the
synthesis of a wide spectrum of novel products for different applications.
The heteroannulations of coumarin usually require either forcing
conditions or relatively longer synthetic pathways. In addition, the read-
ily available dienophiles are a class of important organic synthons that
have exciting chemistry.
In view of the considerable chemical reactivity of activated dieno-
philes, we felt it would be valuable to investigate their reaction with
strongly nucleophilic coumarin derivatives. In addition, phenanthridine
alkaloids (e.g., Amaryllidaceae alkaloid) are known to inhibit protein
synthesis in eukaryotic cells; they exhibit antineoplastic activity in ovar-
ian sarcoma and lymphatic leukemia and therefore are considered antimi-
totics. In this article, we report our study on the synthesis of some new
arylazobenzimidazolo and pyridoimidazolo phenanthridine derivatives
of potential biological activity. Thus, we have found that fusion of a
coumarin derivative (8) with different aryl aldehydes in the presence of
a catalytic amount of piperidine gave the corresponding 4-arylidene
coumarin derivatives (9a–d) (Scheme 3).
The structures of compounds 9a–d were proposed on the basis of
elemental analyses and spectral data. In general, the IR spectra of these
compounds showed absorption bands at 3350, 1730, 1600, and 1175 cmꢀ1
,
attributable to the stretching frequencies of OH, c-lactonic carbonyl,
1
C¼C, and C–O–C functional groups, respectively. The H NMR spectra

2958
A. El-Shafei et al.
Scheme 3. Synthesis of 4-arylidene coumarin derivatives.
displayed a multiplet at 6.93–7.69 ppm, representing the aromatic
protons, and a singlet peak at d 6.89 ppm for the C3 proton. In addition,
two doublets appeared at 5.6 and 5.8 ppm, due to two olefinic protons. In
13C NMR, the carbonyl carbon appeared at 169.01 ppm.
The coumarin derivative (9a) thus formed reacts with different
dienophiles (10a–d) in dichloromethane (DCM) at room temperature to
give the corresponding endo-cyclo adducts 3-hydroxy-8-substituted-9-
phenyl-6a,7,8,9-tetrahydro-6H-benzo[c]chromen-6-one derivatives (11a–d)
(Scheme 4).
The structures (11a–d) were established by both elemental and spec-
1
tral results. For example, their H NMR spectra, in general, showed a
complex pattern that confirmed structure A rather than B. The 1H
NMR spectrum of 11b showed a multiplet at 2.17 ppm due to C7 protons,
a multiplet at d 3.31 for the C8 proton, two doublets at d 3.62 and d 5.78
for a C9 and C10 protons, a doublet doublet at d 2.78 ppm for C6a proton,
and a multiplet of the aromatic protons at d 6.5–7.3 ppm. The IR spec-
trum showed frequencies at 3350, 1730, 1600, and 1170 cmꢀ1 due to
OH, CO, C¼C, and C–O–C functional groups respectively, whereas
the 13C NMR spectrum showed C-1 (128), C-2 (112.4), C-3 (156.9),
C-4 (108.5), C-6 (169.0), C-7 (33.3), C-8 (38.8), C-9 (141.4), C-10
(120.7), C-11 (144.2), C-12 (45.8), C-13 (120.4), C-14 (152.2), C-8 phenyl
(125.8–128.6), and C-9 phenyl (125.7–128.3).
1
The H NMR spectra of 11a, c, and d showed a pattern similar to
that of structure 11b in addition to a singlet at d 3.73 attributed to
OCH3 protons in structure 10c, while in structure 10d the 1H NMR spec-
trum revealed a triplet at d 1.02 ppm attributed to CH2CH3 and a quartet
at 3.55 ppm for CH2CH3 protons. In structure 10a, it showed a doublet at
d 1.9 ppm due to the CH2Br proton and a multiplet at d 3.4 ppm attribu-
table to the C8 proton.

Novel Coumarin and Phenanthridine
2959
Scheme 4. Synthesis of 3-hydroxy-9-phenyl tetrahydrobenzochromenone derivatives.
MOLECULAR MODELING
The Diels–Alder reaction between the diene (compound 9a) and dieno-
philes (compounds 10a–d) can lead to two stereoisomeric products
through two different transition states: endo and exo. With this in mind,
equilibrium molecular geometry for the exo and endo adducts of
compounds 11a–d were predicted using ab initio calculations at the
Hartree–Fock (HF) level using the basis set 6-31 G (d, p). Table 1 shows
the calculated heat of formation, the energy value of HOMO-LUMO
gap, and dipole moment for the possible stereoisomers of compounds
11a–d calculated following geometry optimization using the same level
of theory and basis set. The heat of formation data presented in Table 1
clearly show that the endo adducts are more stable than the exo adduct
for compounds 11a–d by about 0.756–6.813 kcal=mol. Moreover, the
HOMO-LUMO energy gap for the endo adducts is larger than that of
the exo adducts, which indicates that the endo adducts are more stable.
It was also observed that the dipole moments of the endo adducts are
greater than those of the exo adducts. Based on the calculated heat of for-
mation and HOMO-LUMO energy gap of the endo and exo adducts, it

2960
A. El-Shafei et al.
Table 1. Total heat of formation, energy value of HOMO-LUMO gap, and
dipole moment for compounds 11a–d
Total heat of
formation (Hartree)
HOMO-LUMO
gap (eV)
Dipole moment
(Debye)
Compound 11
Endo
Exo
Endo
Exo
Endo
Exo
a
b
c
ꢀ3486.935a ꢀ3486.925 11.123
ꢀ1108.138b ꢀ1108.127 11.109
ꢀ1222.019c ꢀ1222.008 11.102
ꢀ1144.276d ꢀ1144.274 11.113
10.910
10.837
10.754
11.06
5.657
4.280
3.606
6.153
5.656
4.156
3.063
4.467
d
Note. 1 Hartree ¼ 627.5 kcal=mol.
aEndo ¼ Exoꢀ6.139 (kcal=mol).
bEndo ¼ Exoꢀ6.813 (kcal=mol).
cEndo ¼ Exoꢀ6.717 (kcal=mol).
dEndo ¼ Exoꢀ0.756 (kcal=mol).
became clear that the endo adducts are thermodynamically more
favorable than the exo adducts.
To further investigate the reaction stereospecificity between
compounds 9a and 10a, the HOMO and LUMO energy values of each
compound were computed at the HF level of theory using the basis set
6-31 G (d,p), and the molecular orbital (MO) isosurface was examined.
It was found that the energy gap between the HOMO of compound 9a
and the LUMO of compound 10a is smaller than that of the LUMO
of compound 9a and HOMO of compound 10a. Hence, it was concluded
that the reaction proceeds through the interaction of the HOMO of
compound 9a with the LUMO of compound 10a.
To gain more understanding about the stereospecificity, the HOMO
coefficients of compounds 9a and the LUMO coefficients of 10a were
examined, and it was shown that carbon 20 of the former carries a bigger
coefficient than carbon 15 (Fig. 1a), and carbon 2 of the latter carries a
slightly bigger coefficient than that of carbon 1 (Fig. 1b), which favors
endo adduct formation. Figures 1a and 1b show the HOMO and LUMO
isosurface of compounds 9a and 10a, respectively, superimposed on their
optimized molecular geometry computed using ab initio at the HF level
of theory.
To gain more insights and deeper understanding of the kinetics of
formation of compounds 11a–d, the optimized geometry of the transition
state of each product was predicted for both the exo and endo adducts,
and their final energies were computed and compared with each other
using PM3 parameters. Table 2 shows the heat of formation and the
energy of the optimized geometry of the transition state of the exo and

Novel Coumarin and Phenanthridine
2961
Figure 1. (a) HOMO isosurface of compound 9a, and (b) the LUMO isosurface
of compound 10a.
endo adducts of compounds 11a–d. The data in Table 1 clearly indicates
that the endo adducts are thermodynamically and kinetically more
favorable than the exo adducts.
Figure 2a shows the potential energy surface for the reaction of
compound 9a with compound 10a. The potential energy (Fig. 2b) for
the saddle point of compound 11a with the ball cursor in the middle
of the yellow band corresponds to the equilibrium molecular geometry
of the transition state (Fig. 2c) of compound 11a, which shows the bond
formation between the diene and dienophile starting at the bond
˚
distance 2.2 A.
Coupling of 11b with some selected diazotized aromatic amines
(12a–e) afforded the corresponding 3-hydroxyl-8,9-diphenyl-4-arlyazo-
6a,7,8,9-tetrahydrobenzo[c]chromen-6-one derivatives (13a–e). Structures
Table 2. Total heat of formation (HF) and final energy of the transition-state
compound (11a–d) calculated using PM3 parameters
HF (kcal=mol), PM3
Endo Exo
Energy of transition state (kcal=mol)
Compound 11
Endo
Exo
a
b
c
ꢀ17.329 ꢀ15.311
10.842 12.8750
45.415
72.276
34.126
ꢀ38.145
47.055
73.621
35.497
ꢀ37.5077
ꢀ28.229 ꢀ25.209
d
ꢀ102.105 ꢀ99.464

2962
A. El-Shafei et al.
Table 3. Fragments and their relative abundance of
compound 2
Mass
RA (%)
RIC (%)
51
63
77
89
23.42
4.15
25.97
4.85
5.77
6.44
1.14
7.14
1.33
1.59
2.28
1.76
3.60
1.65
3.19
5.74
3.91
1.47
4.74
1.15
27.49
7.81
1.32
1.61
113
135
137
138
139
140
164
165
166
193
194
270ꢁ
271
272
335ꢁꢁ
8.30
6.41
13.08
59.92
11.60
20.89
14.21
5.35
17.23
5.56
100.00
28.42
4.80
5.86
e ¼ 363.79
ꢁBase peak. ꢁꢁMþ (molecular ion peak).
13a–e were established on the basis of both elemental and spectral data.
1
The H NMR spectrum of compound 13a revealed a multiplet at d 2.17
due to CH2 protons, a doublet at d 2.79 (C6a proton), two doublets at d
3.31 (C8 proton), two doublets at d 3.62 (C9 proton), and two doublets
at d 5.78 (C10 proton), in addition to a multiplet of aromatic protons
at d 6.7–7.93. On the other hand, the IR spectrum of compounds 13a–e
showed absorption frequencies at 3310, 1730, 1610, 1580, and 1170cmꢀ1
due to OH, c-lactonic carbonyl, C¼C, N¼N, and C–O–C functional
groups, respectively.
Condensation of 13a with o-phenylenediamine and=or 2,3-diamino
pyridine in boiling glacial acetic acid in the presence of a catalytic amount
of freshly fused sodium acetate gave the corresponding 2,3-diphenyl-8-
phenylazo-1,2,3,13b-tetrahydro-8b,13-diaza-indeno[1,2-I]phenanthren-
7-ol(14a) and its 8b, 12,13-triaza derivative (14b), respectively.
Structures 14a and b were suggested for the reaction product on the
basis of elemental analyses and spectral evidence. In addition, structures
14a and b were confirmed by independent synthesis via the condensation

Novel Coumarin and Phenanthridine
2963
Figure 2. (a) Potential energy surface for the reaction of compound 9a with com-
pound 10a, (b) potential energy surface showing the transition state of compound
11a, and (c) the optimized geometry of the transition state of compound 11a.
of coumarin derivative 11b with o-phenylenediomine and=or 2,3-
diaminopyridine in the presence of freshly fused sodium acetate in glacial
acetic acid to give the corresponding benzimidazolo or pyridoimidazolo
phenarthridine derivatives (15a and b) followed by coupling with the
appropriate diazotied aromatic amine (12a) to give the corresponding
8-phenylazo derivatives (14a and b). Elemental analysis and spectral data
are in good agreement with structures of the hitherto prepared azo dyes
(cf. Scheme 5). The IR spectrum of 14a showed the disappearance of the
bands at 1730 and 1170 cmꢀ1 of d-carbonyl lactone and C–O–C func-
tional groups, and a new band appeared at 1625 cmꢀ1 due to the absorp-
tion stretching frequency of the C¼N function group. The 13C NMR
1
spectrum revealed a signal of C¼N at 141.5 ppm, and in the H NMR
spectrum, the C13a proton appeared as a doublet at a lower field
(d 3.24 ppm) than that of compound 13a because of the electronegativity
of nitrogen atoms in compound 14a (cf. Experimental section). The mass
spectrum of compound 2 exhibits abundant parent ions for the structure
Ar1SO2C6H5, where Ar1 represents the iminobenzocoumarin moiety. It
was found that the prominent peaks in the mass spectra were due to
Ar1SOþ, Ar1Oþ, C6 H5 SOþ., and C6H5Oþ. as shown in Fig. 3. Also,
the ions Ar1SOþ2 ꢂ are of low abundance. On the other hand, fragmenta-
tion does occur in which neutral Ar1SO2 fragments seem to be eliminated.
Both Arþ1 ꢂ and C6Hþ5 ꢂ ions are observed at high abundance.
An ion of mass corresponding to M–SO2C6H5 units (Arþ1 ꢂ) with a loss
mass unit of 27 gives a neutral fragment (Ar1–HCN) of mass 167 (Fig. 4).

2964
A. El-Shafei et al.
Figure 3. Fragmentation pattern of arylsulfonyl compounds.
An ion m=z 139 may find its origin in the loss of carbon monoxide
from mass of 167. The great intensity of the ions 271 and 270 demon-
strates the overall stability of these ions, while the formation of an m=z
Figure 4. General route of fragmentation of coumarin derivatives.

Novel Coumarin and Phenanthridine
2965
Scheme 5. Synthesis of tetrahydrodiaza- and triaza-indenophenanthrene derivatives.
138 fragment is reminiscent of the behavior of furan and may conceiva-
bly proceed from ion B with the production of ion 138 or a related tro-
plium species. It is postulated that the latter ion has the nephthcyclo
propenyl structure and is formed in a manner similar to the C3H3þꢂ
ion in furan.
Compound 3 showed a similar fragmentation behavior route as that
discussed for compound 2 (cf. Fig. 4).
EXPERIMENTAL
General
All melting points are recorded on Gallenkamp electric melting-point
apparatus and are uncorrected. The IR spectra t cmꢀ1 (KBr) were
obtained on a Perkin-Elmer IR spectrophotometer model 157. The H
NMR spectra were recorded on a Varian spectrometer at 200 MHz using
1

2966
A. El-Shafei et al.
tetramethylsilane (TMS) as an internal reference and dimethylsulfoxide
(DMSO)-d6 as solvent. The mass spectra (EI) were run at 70 eV with
Kratos MS equipment and=or a Varian MAT 311 A spectrometer.
Molecular Modeling
All molecular geometries were fully optimized using either Gaussian
03 W[17] or CAChe 12.12.33.[18] In the case of transition-state calcula-
tions, harmonic vibration frequencies were calculated using PM3 imple-
mented in CAChe for all stationary points to verify that for energy
minima all frequencies are real but for the transition state there is only
one imaginary frequency. In the case of ab initio calculations, geometry
optimization was performed using HF=6–31 G (d,p).[19]
Synthesis of 2-Imino-3-phenylsulfonyl-benzo[f]chromene (2) and 2-Imino-3-
phenylsulfonyl Coumarin (4)
2-Hydroxy-1-naphthaldehyde and=or salicylaldehyde (0.0 l mol) were
added to a solution of phenylsulfonyl acetonitrile (1, 0.01 mol) in absolute
ethanol (30 ml) in the presence of a catalytic amount of triethylamine
(4 drops). The reaction mixture was refluxed for 4 h and allowed to cool
to room temperature. The resulting precipitate was filtered, dried, and
recrystallized from ethanol to yield compounds 2 and 4, respectively
(cf. Table 1). Compound 2: 185ꢃC; 76%; IR (KBR) nmax cmꢀ1: 3150
1
(NH), 1561 (phenyl); H NMR (CDCl3) d 7.3–8.5 (m, 9H, Ar-H), 8.4 (d,
1H, C9-H), 8.45 (d, 1H, C10-H), 8.8 (s, 1H, NH exchangeable with D2O),
9.2 (s, 1H, C4-H); m=z 335 (Mþ, 10%); calcd. for C19H13NO3S: 335.38;
C, 68.1; H, 3.9; found: C, 68.1; H, 4.1. Compound 4: 223ꢃC; 66%; IR
(KBR) nmax cmꢀ1: 3120 (NH), 1550 (phenyl); 1H NMR (CDCl3) d
7.3–8.5 (m, 9H, Ar-H), 8.7 (s, 1H, C4-H), 9.7 (s, 1H, C4-H); m=z 285
(Mþ, 20%); calcd. for C15H11NO3S: 285.32; C, 63.2; H, 3.9; found: C,
63.2; H, 3.9.
Synthesis of 3-Phenylsulfonyl-2H-benzo[f]-2-chromenone (3)
and 3-Phenylsulfonyl-2-coumarinone (5)
A solution of compounds 2–4 (0.01 mol) in a mixture of conc. HCl and
ethanol (1:1, 20 ml) was heated for 15 min. The reaction mixture was left
to stand at room temperature overnight, and the solid product was
filtered off and recrystallized from ethanol to give compounds 3 and 5,

Novel Coumarin and Phenanthridine
2967
respectively (cf. Table 1). Compound 3: 218ꢃC; 55%; IR (KBR) nmax cmꢀ1
:
1700 (d-lactonic CO), 1555 (phenyl); 1H NMR (CDCl3) d 7.55–8.25
(m, 9H, Ar-H), 8.4 (d, C9-H), 8.50 (d, 1H, C10-H), 9.2 (s, 1H, C4-H);
m=z 336 (Mþ, 15%); calcd. for C19H12O4S: 336.36; C, 67.9; H, 3.6; found:
C, 67.3; H, 3.5. Compound 5: 244ꢃC; 50%; IR (KBR) nmax cmꢀ1: 1710
1
(d-lactonic CO), 1550 (phenyl); H NMR (CDCl3) d 7.5–8.5 (m, 9H,
Ar-H), 9.2 (s, 1H, C4-H); m=z 286 (Mþ, 35%), calcd. for C15H10O4S:
286.30; C, 62.9; H, 3.5; found: C, 62.8; H, 3.3.
Synthesis of N-(p-Methoxyphenyl)-3-phenylsulfonylquinolin-2-one (7)
A mixture of compound 3 (0.01 mol) and=or compound 5 (0.01 mol)
and p-anisidine (0.01 mol) in glacial acetic acid (30 ml) containing
freshly fused sodium acetate (0.3 g) was refluxed for 4 h. The reaction
mixture was left to cool at room temperature. The precipitated solid
materials were filtered off, dried well and recrystallized from acetic acid
to yield compounds 6 and 7, respectively (cf. Table 1). Compound 6:
265ꢃC; 43%; IR (KBR) nmax cmꢀ1: 1680 (amidic CO), 1540 (phenyl);
1H NMR (CDCl3) d 3.74 (s, 3H, OCH3), 8.45 (d, 1H, C9-H), 8.6 (d,
1H, C10-H), 7.4–8.35 (m, 9H, Ar-H), 9.3 (s, 1H, C4-H); calcd. for
C26H19NO4S: 441.5; C, 70.7; H, 4.3; found: C, 70.6; H, 4.1. Compound
7: 282ꢃC; 40%; IR (KBR) nmax cmꢀ1: 1680 (amidic CO), 1550 (phenyl);
1H NMR (CDCl3) d 3.75 (s, 3H, OCH3), 7.30–8.40 (m, Ar-H), 9.1 (s,
1H, C4-H); calcd. for C22H17NO4S: 391.44; C, 67.5; H, 4.3; found: C,
67.5; H, 4.3.
Synthesis of 7-Hydroxy-4-arylidene Coumarino Derivatives (9a–d)
A mixture of coumarin derivative (8, 0.01 mol) and different aryl
aldehydes (0.01 mol) was heated in an oil bath at 150ꢃC for 3 h in the
presence of a catalytic amount of piperdine. The reaction mixture was
recrystallized from acetic acid to yield the corresponding
4-arylidene-coumarino derivatives 9a–d (cf. Table 1). Compound 9a:
146ꢃC; 85%; IR (KBR) nmax cmꢀ1: 3350 (OH), 1720 (d-lactonic CO),
1
1600 (C¼C), 1175 (C–O–C); H NMR (CDCl3) d 5.6–5.8 (two-d, 2H,
CH¼CH), 6.89 (s, 1H, C3-H), 6.93–7.69 (m, 8H, Ar-H); calcd. for
C18H14O2: 262.30; C, 77.3; H, 4.6; found: C, 77.1; H, 4.5. Compound
9b: 160ꢃC; 73%; IR (KBR) nmax cmꢀ1: 3315 (OH), 1720 (d-lactonic
1
CO), 1600 (C¼C), 1175 (C–O–C), 1350, 1530 (NO2); H NMR (CDCl3)
d 5.6, 5.8 (2d, 2H, CH¼CH), 6.89 (s, 1H, C3-H), 6.93–7 (m, 7H, Ar-H);
calcd. for C18H13NO4: 307.30; C, 66.0; H, 3.6; found: C, 66.0; H, 3.5.

2968
A. El-Shafei et al.
Compound 9c: 173ꢃC; 65%; IR (KBR) nmax cmꢀ1: 3380 (OH), 1700 (c-
1
lactonic CO), 1600 (C¼C), 1180 (C–O–C); H NMR (CDCl3) d 5.6, 5.8
(2d, 2H, CH¼CH), 6.9 (s, 1H, C3-H), 6.95–7.80 (m, 7H, Ar-H); calcd.
for C18H13ClO2: 296.75; C, 68.3; H, 3.7; found: C, 68.2; H, 3.5.
Compound 9d: 182ꢃC; 70%; IR (KBR) nmax cmꢀ1: 3315 (OH), 1720
(c-lactonic CO), 1600 (C¼C), 1175 (C–O–C), 1350, 1530 (NO2); 1H
NMR (CDCl3) d 5.6, 5.8 (2-d, 2H, CH¼CH), 6.9 (s, 1H, C3-H),
6.95–7.80 (m, 7H, Ar-H); calcd. for C18H13ClO2: 296.75; C, 66.0; H,
3.6; found: C, 66.0; H, 3.5.
Synthesis of 3-Hydroxy-9-phenyl-6a,7,8,9-tetrahydrobenzo[c]
chromen-6-one Derivatives (11a–d)
A solution of coumarin derivative 9a (0.01 mol) and vinyl derivatives
10a–d (0.01 mol) in DCM (20 ml) was left to stand at room temperature
overnight. The precipitated solid product was filtered off, dried well, and
recrystallized from dioxane to give compounds 11a–d (cf. Table 1).
Compound 11a: 201ꢃC; 77%; IR (KBR) nmax cmꢀ1: 3350 (OH), 1720
1
(c-lactonic CO), 1610 (C¼C), 1770 (C–O–C); H NMR (CDCl3) d 1.9
(d, 2H, CH2Br), 2.17 (m, 2H, C7-H), 2.78 (d-d, 1H, C6a-H), 3.4 (m,
1H, C8-H), 3.62 (d, 1H, C9-H), 5.78 (d, 1H, C10-H), 6.5–7.3 (m, 8H,
Ar-H); calcd. for C20H17BrO3: 385.25; C, 62.3; H, 4.4; found: C, 62.1;
H, 3.9. Compound 11b: 223ꢃC; 60%; IR (KBR) nmax cmꢀ1: 3350 (OH),
1
1730 (c-lactonic CO), 1600 (C¼C), 1170 (C–O–C); H NMR (CDCl3) d
2.17 (m, 2H, C7-H), 2.78 (d-d, 1H, C6a-H), 3.31 (m, 1H, C8-H), 3.62
(d, 1H, C9-H), 5.78 (d, 1H, C10-H), 6.5–7.3 (m, 13H, Ar-H); 13C NMR
d C-1 (128), C-2 (112.4), C-3 (156.9), C-4 (108.5), C-6 (169.0), C-7 (33.3),
C-8 (138.8), C-9 (141.4), C-10 (120.7), C-11 (144.2), C-12 (45.5), C-13
(120.4), C-14 (152.2), C-8-phenyl (125.8–128.6); calcd. for C25H20O3:
368.42; C, 81.5; H, 5.4; found: C, 81.3; H, 4.9. Compound 11c: 210ꢃC;
72%; IR (KBR) nmax cmꢀ1: 3320 (OH), 1710 (c-lactonic CO), 1180 (C–
1
O–C); H NMR (CDCl3) d 2.17 (m, 2H, C7-H), 2.78 (d-d, 1H, C6a-H),
3.31 (m, 1H, C8-H), 3.62 (d, 1H, C9-H), 3.72 (s, 3H, OCH3), 5.78 (d,
1H, C10-H), 6.5–7.3 (m, 12H, Ar-H); calcd. for C26H22O4: 398.45; C,
78.4; H, 5.5; found: C, 78.5; H, 5.2. Compound 11d: 272ꢃC; 68%; IR
(KBR) nmax cmꢀ1: 3300 (OH), 1740 (carbonyl ester), 1710 (d-lactonic
CO), 1640 (C¼N), 1170 (C–O–C); 1H NMR (CDCl3) d 1.02 (t, 3H,
CH2CH3), 2.17 (m, 2H, C7-H), 2.75 (d-d, 1H, C6a-H), 3.31 (m, 1H, C8-
H), 3.55 (q, 2H, CH2CH3), 3.62 (d, 1H, C9-H), 5.78 (d, 1H, C10-H),
6.5–7.3 (m, 8H, Ar-H); calcd. for C22H20O5: 364.39; C, 72.5; H, 5.5;
found: C, 72.2; H, 5.1.

Novel Coumarin and Phenanthridine
2969
Synthesis of 3-Hydroxy-8,9-diphenyl-4-arylazo-
6a,7,8,9-tetrahydrobenzo[c]chromen-6-one Derivatives (13a–e)
A well-stirred solution of appropriate aryl amines (12a–e, 0.2 mol) in
2 N HCl (125 ml) was cooled in an ice bath and diazotized with
0.1 N sodiuꢃm nitrite solution (100 ml). The reaction mixture was stir-
red at 0–5 C for 1 h. The cold diazonium solution was added drop-
wise to a well stirred cold solution of compound 11b (0.2 mol) in
sodium hydroxide solution (5%, 30 ml). The reaction mixture was stir-
red for 2 h until coupling was complete. The precipitated solid material
was filtered off, washed with water, dried well, and recrystallized from
aqueous ethanol to give 13a–e derivatives (cf. Table 1). Compound
13a: 260ꢃC; 62%; IR (KBR) nmax cmꢀ1: 3310 (OH), 1730 (d-lactonic
CO), 1610 (C¼), 1580 (N¼N), 1170 (C–O–C); 1H NMR (CDCl3) d
2.17 (m, 2H, C7-H), 2.79 (d-d, 1H, C6a-H), 3.31 (m, 1H, C8-H), 3.61
(d, 1H, C9-H), 5.78 (d,d-1H, C10-H), 6.7–7.93 (m, 17H, Ar-H); 13C
NMR C-1 (130.2), C-2 (112.7), C-3 (151.1), C-4 (132.5), C-6 (169.0),
C-6a (45.8), C-7 (33.3), C-8 (138.8), C-9 (141.5), C-10 (120.2),
C-10a (144.2), C-11a (120.7), C-12a (146.4), N¼N-phenyl (122.7–152.5)
C-8-phenyl (125.8–128.6), C-9-phenyl (125.7–128.3); calcd. for C31H24
N2O3: 472.53; C, 78.8; H, 4.1; found: C, 78.3; H, 4.5. Compound 13b:
281ꢃC; 55%; IR (KBR) nmax cmꢀ1: 3310 (OH), 1725 (d-lactonic CO),
1610 (C¼C), 1580 (N¼N), 1530 (NO2 sym), 1350 (NO2 sym), 1170
1
(C–O–C); H NMR (CDCl3) d 2.20 (m, 2H, C7-H), 2.79 (d, 1H, C6a-
H), 3.32 (d, d, 1H, C8-H), 3.60 (d, d, 1H,C9-H), 5.8 (d,d-1H, C10-H),
6.7–7.93 (m, 16H, Ar-H); calcd. for C31H23N3O5: 517.53; C, 72.0; H,
4.5; found: C, 71.6; H, 4.2. Compound 13c: 279ꢃC; 58%; IR (KBR)
n
max cmꢀ1: 3310 (OH), 1720 (d-lactonic CO), 1600 (C¼C), 1580
1
(N¼N), 1180 (C–O–C); H NMR (CDCl3) d 1.90 (s, 3H, CH3), 2.18
(m, 2H, C7-H), 2.79 (d, 1H, C6a-H), 3.40 (d, d, 1H, C8-H), 3.60 (d, d,
1H, C9-H), 5.78 (d, d-1H, C10-H), 6.65–7.8 (m, 16H, Ar-H); calcd. for
C32H26N2O3: 486.56; C, 79.0; H, 5.4; found: C, 79.2; H, 5.1. Compound
13d: 285ꢃC; 49%; IR (KBR) nmax cmꢀ1: 3380 (OH), 1710 (d-lactonic CO),
1620 (C¼C), 1580 (N¼N), 1175 (C–O–C); 1H NMR (CDCl3) d 2.18
(m, 2H, C7-H), 2.79 (d, 1H, C6a-H), 3.45 (d, d, 1H, C8-H), 3.60 (d, d,
1H, C9-H), 3.90 (s, 3H, OCH3), 5.75 (d, d-1H, C10-H), 6.70–7.90
(m, 16H, Ar-H); calcd. for C32H26N2O4: 502.56; C, 76.5; H, 5.2; found:
C, 76.5; H, 5.1. Compound 13e: 252ꢃC; 55%; IR (KBR) nmax cmꢀ1: 3300
(OH), 1710 (d-lactonic CO), 1600 (C¼C), 1575 (N¼N), 1185 (C–O–C);
1H NMR (CDCl3) d 2.17 (m, 2H, C7-H), 2.77 (d, 1H, C6a-H), 3.33
(d, d, 1H, C8-H), 3.61 (d, d, 1H, C9-H), 5.75 (d, d-1H, C10-H),
6.7–7.91 (m, 16H, Ar-H); calcd. for C31H23ClN2O3: 506.98; C, 73.5; H,
4.5; found: C, 73.2; H, 4.2.

2970
A. El-Shafei et al.
Synthesis of 2,3-Diphenyl-1,2,3,13b-tetrahydro-8b,13-diaza-indeno(1,2-I)
phenthren-7-o1 (14a) and Its 8b,12,13-Triaza Derivative (14b)
Method A
A mixture of compound 13a (0.005 mol) and o-phenylenediamine
(0.005 mol) and=or 2,3-diaminopyridine (0.005 mol) was refluxed in
glacial acetic acid (30 ml) in the presence of freshly fused sodium acetate
(0.3 g) for 6 h. The reaction mixture was left to stand overnight for
complete precipitation. The resulting precipitate was filtered, dried, and
recrystallized from acetic acid to yield the corresponding 14a and b,
respectively (cf. Table 1).
Method B
A well-stirred solution of aniline (0.2 mol) in 2 N HCl (125 ml) was cooled in
an ice bath (0–5ꢃC), diazotized with 0.1 N sodium nitrite solution (100 ml),
and stirred for 1 h at 0–5ꢃC. The diazonium solution was added dropwise
to a well-stirred cold solution of compounds 15a and b (0.2 mol) in sodium
hydroxide solution (5%, 30 ml). The reaction mixture was stirred for 2 h until
coupling was complete. The resulting precipitate was filtered, washed with
water, dried, and recrystallized from aqueous ethanol to yield compounds
14a and b. Compound 14a: >300ꢃC; 40%; IR (KBR) nmax cmꢀ1: 3340
1
(OH), 1625 (C¼N), 1600 (C¼C), 1580 (N¼N); H NMR (CDCl3) d 2.3
(m, 2H, CH2), 3.23 (d, 1H, C13a-H), 3.31 (m, 1H, C2-H), 3.62 (d, 1H, C3-
H), 5 (s, 1H, OH), 5.78 (d, 1H, C4-H), 6.9–7.93 (m, 21H, Ar-H); 13C
NMR: C-1 (90.3), C-2 (42.8), C-2-phenyl (125–138.8), C-3 (41.8), C-3-phenyl
(135.7–139.4), C-4 (120.7), C-4a (144.2), C-5 (130.7), C-6 (115.4), C-7 (151.6),
C-8 (132.1), N¼N-phenyl (122.7–152.5), C-8a (130), C-8b (120.3), C-9a
(137.9), C-9 (115.4), C-10 (122.9), C-11 (122.9), C-12 (115.4), C-12a (137.9),
C13a (141.5), (36.3); calcd. for C37H28N4O: 544.64; C, 81.6; H, 5.2; found:
C, 81.4; H, 4.6. Compound 14b: >300ꢃC; 46%; IR (KBR) nmax cmꢀ1
:
1
3350 (OH), 1620 (C¼N), 1600 (C¼C), 1580 (N¼N); H NMR (CDCl3) d
2.20 (m, 2H, CH2), 2.23 (d, 1H, C13a-H), 3.34 (m, 1H, C2-H), 3.62 (d, 1H,
C3-H), 5.0 (s-1H, OH), 5.57 (d, 1H, C4-H), 6.85–7.42 (m, 20H, Ar-H); calcd.
for C36H27N5O: 545.63; C, 79.3; H, 5.0; found: C, 79.1; H, 4.7.
Synthesis of 2,3-Diphenyl-1,2,3,13b-tetrahydro-8b,13-diaza-indeno
(1,2-I)phenanthren-7-ol (15a) and Its 8b,12,13-Triaza Derivatives (15b)
Equimolar amounts of compound 11a (0.005 mol) and o-phenylendia-
mine (0.005 mol) and=or 2,3-diamino pyridine (0.005 mol) were refluxed

Novel Coumarin and Phenanthridine
2971
in glacial acetic acid (30 ml) in the presence of freshly fused sodium
acetate (0.3 g m) for 4 h and allowed to cool to room temperature.
The resulting precipitate was filtered, dried, and recrystallized from
acetic acid to yield compounds 15a and b (cf. Table 1). Compound
15a: 277ꢃC; 50%; IR (KBR) nmax cmꢀ1: 3310 (OH), 1640 (C¼N),
1600 (C¼C); 1H NMR (CDCl3) d 2.23 (m, 2H, CH2), 3.21 (d, 1H,
C13a-H), 3.25 (m, 1H, C2-H), 3.61 (d, 1H, C3-H), 5.2 (s-1H, OH),
5.71 (d, 1H, C4-H), 6.6–7.4 (m, 17H, Ar-H); calcd. for C31H24N2O:
440.54; C, 84.6; H, 5.5; found: C, 84.1; H, 4.9. Compound 15b:
283ꢃC; 43%; IR (KBR) nmax cmꢀ1: 3320 (OH), 1640 (C¼N), 1600
(C¼C); 1H NMR (CDCl3) d 2.23 (m, 2H, CH2), 2.21 (d, 1H, C13a
-
H), 3.35 (m, 1H, C2-H), 3.6 (d, 1H, C3-H), 5.3 (s-1H, OH), 5.51 (d,
1H, C4-H), 6.5–7.4 (m, 16H, Ar-H); calcd. for C30H23N3O: 441.52; C,
81.6; H, 5.2; found: C, 81.6; H, 5.1.
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