A convenient synthesis of partially reduced benzo[c]phenanthrenes, its ketals and ketones

Article abstract of DOI:10.1016/j.tet.2009.12.026

A concise and convenient synthesis of various partially reduced 6-sec-amino-1,2,3,4,7,8-hexahydro-, 6-sec-amino-1,2,7,8-tetrahydrobenzo[c]phenanthrene-5-carbonitriles, 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenanthrene-2-one-5-carbonitrile cycloalkene

Full text of DOI:10.1016/j.tet.2009.12.026

Tetrahedron 66 (2010) 1458–1464
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A convenient synthesis of partially reduced benzo[c]phenanthrenes,
its ketals and ketonesq
,
d
,
b
c
b
Ramendra Pratap a , Resmi Raghunandan , Abhishek Kumar Mishra , P.R. Maulik ,
*
V.P. Gupta c, Vishnu Ji Ram a
,d,
*
a Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow–226 001, India
b Molecular & Structural Biology Division, Central Drug Research Institute, Lucknow–226 001, India
c Department of Physics, Lucknow University, Lucknow-226007, India
d Institut fu¨r Organische Chemie Universita¨t des Saarlande, Saarbru¨cken-66123, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A concise and convenient synthesis of various partially reduced 6-sec-amino-1,2,3,4,7,8-hexahydro-,
6-sec-amino-1,2,7,8-tetrahydrobenzo[c]phenanthrene-5-carbonitriles, 6-sec-amino-3,4,7,8-tetrahydro-
1H-benzo[c]phenanthrene-2-one-5-carbonitrile cycloalkene ketals, pendant with electron donor and
acceptor substituents has been described through base catalyzed ring transformation of 2-oxo-4-sec-
amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles by cyclohexanone, 2-cyclohexen-1-one,
1,4-cyclohexanedione monocycloalkene ketals. The acid catalyzed deketalation of 6-sec-amino-3,4,7,8-
tetrahydro-1H-benzo[c]phenanthrene-2-one-carbonitrile ketals led to yield 6-sec-amino-3,4,7,8-tetra-
hydro-1H-benzo[c]phenanthrene-3-carbonitrile-2-ones in excellent yield. We also performed the X-ray
studies of the molecules 3d and 6a to know the degree of non-planarity.
Received 31 October 2009
Received in revised form
2 December 2009
Accepted 7 December 2009
Available online 6 January 2010
Keywords:
Benzo[c]phenanthrene
2-Oxo-4-(piperidin-1-yl)-5,6-dihydro-2H-
benzo[h]-chromene-3-carbonitriles
Ring transformation
Ó 2009 Published by Elsevier Ltd.
O
OH
OH
OH
OH
1. Introduction
Polycyclic aromatic hydrocarbons (PAHs) have received con-
siderable attention because of their fascinating chemistry and
unique physical properties due to highly twisted geometry possibly
owing to the over crowding of atoms or groups present in the fjord
region. In these molecules, induced strain is relieved by buckling of
aromatic ring and bending of bonds, assuming helical conforma-
tion. The helicity of polycyclic aromatic hydrocarbons can be fur-
ther increased through bulky substitution in the fjord region as well
as through partial reduction or in combination. There is also
a possibility for the reduced distortion if the twisting in the mol-
ecule is unidirectional. Small helical molecules are of great signif-
icance because of their rich chemistry,1 physical properties,2
technological and industrial applications.1 These molecules have
inherent chirality due to their twisted skeletons and racemize by
inversion and exhibit chirotopic properties, if resolved. The pure
enantiomers are useful as chiral auxiliaries for chiral induction and
as shift reagents in NMR spectroscopy.3
II
III
I
Figure 1. Benzo[c]phenanthrene and their metabolites.
The high prevalence of various polycyclic aromatic hydrocar-
bons in the environment and their threat to cause cancer in humans
has drawn substantial attention. In vivo these metabolize by the
combined action of enzymes P450 and epoxidehydrolase to
diolepoxides that covalently bind to purine base of DNA through
C–N linkage to form stable adduct involving amino group of
deoxyadenosine and deoxyguanosine. When repair enzymes do not
excise these lesions, mutation may occur upon DNA replication,
resulting initiation of tumorigenesis. Benzo[c]phenanthrene (BcP, I)
is relatively weak carcinogen4 present in the environment5 com-
pared to benzo[a]pyrene. The 3,4-dihydrodiol (II) and the corre-
sponding diolepoxide (III) derivatives of BcP are highly potent
carcinogenic metabolites (Fig. 1).6,7
q
CDRI communication No. 7475
One of the most intriguing problems in the study of carcinogenic
hydrocarbons is to establish the correlation between chemical
structure and tumorigenic property. Various theories are proposed
* Corresponding authors. Tel.: þ49 163 1855773 (R.P.); tel.: þ91 522 2612411; fax:
þ91 522 2623405 (V.J.R.).
E-mail addresses: ramendrapratap@gmail.com, vjiram@yahoo.com (R. Pratap).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.12.026

R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
1459
but none of them is satisfactory in all respect. Based on numerous
experimental facts, it has been concluded that partial reduction of
polycyclic aromatic hydrocarbons reduces the carcinogenic prop-
erty, possibly by disrupting the co-planarity of the molecule.6
Various approaches to the synthesis of benzo[c]phenanthrene
ring system are reported7,8 but none of them devoid from shortfalls
of generality, multi-steps sequences with complex work-up and
also impractical for the construction of hindered and partially re-
duced derivatives. The molecules of this ring system are synthe-
sized in multiple steps through the Friedel–Crafts reaction of
1-methallylsuccinic anhydride and benzene followed by reduction
and cyclization.9 Further improvement in the synthetic strategy
shorten the reaction steps and also improved the overall yields of
the final products. Vilsmeier reaction of 1-(4-anisyl)-2-formyl-6-
methoxy-3,4-dihydronaphthalene, which on cyclodehydration and
dehydrogenationprovided 3,10-dimethoxy-5-methyl-5,6,6a,7,8,12b-
O
N
O
NC
COOMe
SMe
CN
O
1. DMSO/KOH
2. EtOH/
+
MeS
HN
1
Scheme 1. Two steps synthesis of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chro-
mene-3-carbonitriles.
As evident from the topography of 2-oxo-4-sec-amino-5,6-
dihydro-2H-benzo[h]chromene-3-carbonitriles 1 that the C2, C4,
and C10b positions are electrophilic in nature. However, the posi-
tion C10b is more electrophilic compared to other positions due to
the presence of an electron-withdrawing CN substituent at position
3 of the chromene ring and extended conjugation that made the
position highly prone to nucleophilic attack.
hexahydrobenzo[c]phenanthrene.10
A novel synthesis of ben-
zo[c]phenanthrene and its 3,4-phenolic derivatives via the key
intermediate, 4-oxo-1,2,3,4-tetrahydrobenzo[c]phenanthrene has
been reported.11 It has also been obtained by alkylation of 1,3-
cyclohexanedione by 2-(2-naphthyl)ethyl iodide, which after
cyclization and dehydrogenation gave 2-phenyl-4-hydroxy-
benzo[c]phenanthrene.12 An efficient and convenient route for
the synthesis of benzo[c]phenanthrene through combined met-
alation, Suzuki/Grignard cross coupling resimen13 has been
reported. An improved synthesis of benzo[c]phenanthrene-3,4-
diol-1,2-epoxide has been achieved from 1-(2-naphthyl)-2-(2-
methoxyphenyl)ethylene, via photocyclization in five steps in
15% overall yield.14 Under a new strategy a cross coupling re-
action of 2-bromo-5-methoxybenzaldehyde with naphthalene-1-
boronic acid produced 2-(1-naphthyl)-5-methoxybenzaldehyde,
followed by acid catalyzed cyclization with methanesulfonic acid
afforded 3-methoxybenzo[c]phenanthrene.15 It has also been
synthesized15 by the photolysis of 2-naphthylstyrene, obtained
from the Wittig reaction of 2-naphthaldehyde and 2,5-dime-
thylbenzyltriphenylphosphonium chloride. Generally, most of
the reported procedures8c,9,13 for the construction of benzo[c]-
phenanthrene derivatives suffer from the harsh reaction condi-
tions and commercially non-availability of reagents.
Various cyclic ketones and 1,4-hexanedione monocycloalkene
ketals have been used as source of carbanions. The methylene
group a- to carbonyl in the cyclic ketones is activated and form
carbanion in the presence of base. Thus, stirring an equimolar
mixture of 1, cyclohexanone 2a and powdered KOH in DMF at room
temperature for 2–3 h followed by usual work-up and purification
of crude product through column chromatography afforded 6-sec-
amino-1,2,3,4,7,8-hexahydrobenzo[c]phenanthrene-5-carbonitriles
3a–d in excellent yields (Scheme 2).
This reaction possibly proceeds through attack of a carbanion at
position C10b of 1 with Michael addition followed by ring closure
with loss of water and carbon dioxide to yield 3a–d (Scheme 2). The
possibility for the formation of mechanistically obvious product 4
was ruled out on the basis of reduced electrophilicity of the C4
carbon due to the presence of amino group, which does not favor
the enolization of Michael adduct formed in the initial step.
Under analogous conditions, the reaction of 1 with 2-cyclo-
hexen-1-one 2b followed the similar course of reaction to yield
partially reduced benzo[c]phenanthrene-3-carbonitriles 3e–g in
good yields, Scheme 2.
A similar reaction of 1 with 1,4-cyclohexanedione was carried
out to obtain 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phenan-
threne-2-one-5-carbonitrile in single step but finally ended with
a complex mixture, possibly due to the side reaction at other car-
bonyl group. To avoid the complexity of reaction, synthetic strategy
was changed by using their monoethylene- and 2,20-dimethyltri-
methylene ketals as a source of carbanion. However, reaction of 1
with 1,4-cyclohexanedione monoalkeneketal 5a and 5b separately
produced 6a–h in excellent yields, Scheme 3.
Attempts to cleave the cyclic ketal ring of 6e by amberlyst-15
failed, but easily cleaved by stirring in formic acid at room tem-
perature to yield 6-sec-amino-3,4,7,8-tetrahydro-1H-benzo[c]phe-
nanthrene-2-ones 7 (Scheme 4).
In order to synthesize highly functionalized 7-helicenes, the ring
transformation of 1 was attempted by 7 under analogous reaction
conditions, but only 7 was recovered. We tried several base and
solvent combinations as KOH/DMSO, NaH/THF, NaH/DMF, KOBut/
DMF and K2CO3/DMF but failed to precede the reaction. We also
carried out this reaction at elevated temperature but no positive
result was achieved, possibly due to steric hindrance, which restricts
the attack of carbanion generated in situ from 7 at C10b of the 1.
X-ray study of partially reduced benzo[c]phenanthrenes: The he-
lical conformation in the benzo[c]phenanthrene has been observed
owing to the distortion of aromatic ring in some way.8c Effect of
partial reduction on acquiring helical conformation in partially
reduced benzo[c]phenanthrenes is not explored due to non-
availability of partially reduced benzo[c]phenanthrenes and is the
concern for present investigation.
The lack of simple and efficient route necessitated the de-
velopment of an economical, efficient and regioselective synthesis of
partially reduced benzo[c]phenanthrenes, their ketals and ketones.
2. Result and discussion
Herein, we report a facile and concise synthesis of functionalized
partially reduced benzo[c]phenanthrenes through a base catalyzed
ring transformation of 2-oxo-4-sec-amino-5,6-dihydro-2H-ben-
zo[h]chromene-3-carbonitriles with cyclohexanone, 2-cyclohexen-1-
one, 1,4-cyclohexanedione monoethylene- and mono-2,20-dime-
thyltrimethylene ketals separately in high yields. The presence of
electron-withdrawing and donating substituents at position 3 and 4
of benzo[h]chromene ring made it indispensable synthon for the
construction of various polycyclic hydrocarbons. The synthetic
potential of 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-
3-carbonitriles is enormous for generating molecular diversity.
The
2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-
carbonitriles, have been prepared in two steps. The first step of the
reaction involves the synthesis of the 2-oxo-4-methylsulfanyl-5,6-
dihydro-2H-benzo[h]chromene-3-carbonitriles16 by stirring a mix-
ture of methyl 2-cyano-3,3-dimethylthioacrylate17 and 1-tetralone
using powdered KOH as a base in DMSO at room temperature. This on
amination with a secondary amine in ethanol at reflux temperature
produced 2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-
carbonitriles in good yields16 and were used for the synthesis of
congested diverse polycyclic aromatic hydrocarbons, Scheme 1.

1460
R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
O
5
N
N
N
O
CN
O
O
O
O
CN
CN
O
+
O
O
O
+
O
O
2b =
2a =
O
1
6
2
1
O
O
KOH DMF
O
O
X
=
O
O
N
O
O
O
O
O
O
CN
Complex reaction
mixture
CN
a
b
O
O
6
Product
Yield (%)
N
CN
O
4
a
b
c
91
N
O
N
N
O
O
CN
OH
CN
CH3
CN
OH
N
H
CN
O
94
89
3
O
Ph
Product
Yield (%)
89
Product
Yield (%)
79
3
a
3
e
N
CN
N
N
CN
CN
O
O
Ph
CH3
CH3
N
N
N
N
92
87
b
c
f
84
87
CN
CN
CN
d
e
f
81
94
89
Ph
Ph
O
O
N
N
N
g
N
CN
CN
CN
O
Ph
O
N
CH3
N
N
95
d
CN
CN
O
Scheme 2. Probable mechanism for the synthesis of 6-sec-amino-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-5-carbonitriles (3a–d) and 6-sec-amino-1,2,7,8-tetrahy-
drobenzo[c]phenanthrene-5-carbonitriles (3e–g).
O
Ph
N
For the study of conformational arrangements of the rings of
benzo[c]phenanthrene, several substituted benzo[c]phenanthrenes
were crystallized for X-ray structural analysis. Diffraction quality
crystals of 6-(4-benzylpiperazin-1-yl)-1,2,3,4,7,8-hexahydrobenzo-
[c]phenanthrene-5-carbonitrile 3d and 6-(piperidin-1-yl)-3,4,7,8-
tetrahydro-1H-benzo[c]phenanthrene-2-one-5-carbonitrile-(2,20-
dimethylene ketal) 6a were obtained in mixture of methanol in
chloroform by slow evaporation at room temperature. The confor-
mation of these compounds with arbitrary numbering is shown as
CN
O
g
91
O
N
CN
O
h
92
ORTEP diagram Figure 2, which indicates
conformation.
a
non-planar
O
The least square plane calculation from X-ray crystallographic
data of 6a indicates that rings A and C are nearly planar. The average
mean plane angle for the twist between the rings A and C is 38.5ꢀ.
The rings B and D adopt half chair conformation. The ring E adopts
Scheme 3. Synthesis of cyclic ethylene ketal of 6-sec-amino-3,4,7,8-tetrahydro–1H-
benzo[c]phenanthrene-2-one, cyclic trimethylene ketal of 6-sec-amino-3,4,7,8-tetra-
hydro–1H-benzo[c]phenanthrene-2-one.

R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
1461
X
The contribution of spiro ring to the helical conformation in 6a
was established by replacing it with hydrogen in 3d, which reduces
the repulsion and thereby torsion angles and degree of induced
non-planarity. Because of electronic repulsion between the two
rings there is remarkable distortion in the case of 6a (w50ꢀ) as
compared to 3d (w39ꢀ)(Table 1 and 2).
X
X
N
N
N
CN
O
CN
O
CN
H.COOH/RT
H.COOH/RT
Table 1
O
O
Selected torsion and mean plane twist angles (ꢀ)
O
7
H3C
6
CH3
6
Comp.
Atoms
Torsion angles
(ꢀ)
Mean plane angle
7
a
b
X
Yield (%)
(Twist angle ꢀ
)
H
99
97
3d
C4a-C5-C6-N2
C6-C5-C13-N1
ꢁ179.04
ꢁ102.71
33.28
A, C 32.55
Benzyl
Scheme 4. Deprotection of cyclic trimethylene- and ethylene ketals.
C12-C12A-C12B-C12C
C1-C12C-C12B-C12A
C1-C12C-C4A-C5
C12C-C12B-C6A-C7
C12B-C12A-C8A-C9
C4a-C5-C6-N2
5.96
174.05
173.92
175.52
178.23
ꢁ179.53
ꢁ40.53
ꢁ9.73
6a
A, C 38.55
C6-C5-C13-N1
C12-C12A-C12B-C12C
C1-C12C-C12B-C12A
C1-C12C-C4A-C5
C12C-C12B-C6A-C7
C12B-C12A-C8A-C9
ꢁ175.39
ꢁ164.43
ꢁ178.36
Figure 2. Displacement ellipsoid plot (30% probability) showing the molecular struc-
ture of 3d and 6a with the atomic-labeling.
Table 2
Selected bond lengths of 3d and 6a
Comp.
Inner C–C
Bond lengths
Outer C–C
bond lengths
an envelope conformation while ring F adopts a full chair confor-
mation. The distance between the non-bonded carbon atoms C1
and C12 is 3 Å, which is shorter than any over crowded molecule
and from van der Waals radii of carbon atoms by 0.4 Å, which in-
duces distortion in the molecule. This strain is relieved either
through stretching and bending of the chemical bonds or buckling
of the aromatic rings.
Similarly the X-ray study of the compound 3d showed that the
average mean plane angle for the twist between the rings A and C is
32.5ꢀ. The distance between the non-bonded carbon atoms C1 and
C12 is 2.994 Å. The torsion angles (C12-C12A-C12B-C12C and C1-
C12C-C12B-C12A) of the compounds 6a are –40.5 and -9.7ꢀ, while
for 3d are 33.28 and 5.9ꢀ. The torsion angles of benzo[c]phenan-
threne and 1,4-dimethyl benzo[c]phenanthrene have 17.3 & 19.0
and ꢁ29.3 & ꢁ18.4ꢀ, respectively. Some of the inner C–C bond
lengths have been lengthened while the outer bonds are closer to
the normal single and double bond lengths. Thus, it is the ring B/C,
that accommodates most of the torsional strain.
3d
C1-C12C 1.522
C5-C6 1.391
C6-C6A 1.381
C6A-C7 1.513
C8-C8A 1.536
C5-C6 1.392
C6-C6A 1.397
C6A-C7 1.515
C8-C8A 1.500
C12C-C12B 1.412
C12B-C12A 1.500
C12A-C12 1.394
C1-C12C 1.518
C12C-C12B 1.416
C12B-C12A 1.481
C12A-C12 1.403
6a
3. Conclusions
We have developed an innovative and concise protocol for the
construction of partially reduced highly functionalized benzo[c]-
phenanthrenes through base catalyzed ring transformation of
2-oxo-4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbon-
itriles by different alicyclic ketones, using potassium hydroxide as
a base and DMF as solvent at room temperature. A methodology for
the introduction of a carbonyl group at position 2 of the ben-
zo[c]phenanthrene has also been developed using 1,4-cyclo-
hexanedione mono ketal as an agent for the ring transformation
followed by acid cleavage of the resulted ketal, providing 2-oxo-4-
Here we showed the arrangement of molecules in the unit cell of
3d and 6a. In case of 3d unit cell contain two molecule and in case
of 6a it contains 4 molecules in unit cell (Fig. 3).
sec-amino-1,2,3,4,7,8-hexahydrobenzo[c]phenanthrene
without
using any oxidizing agent and catalyst. The conformational study
for the selected compounds by X-ray diffraction analysis has also
been done.
4. Experimental
4.1. General
All reactions were conducted in flame-dried glassware. Pre-
coated Merck TLC plates were used for monitoring the reaction.
Column chromatographic separation was performed on neutral
alumina and silica gel (60–120 mesh). IR spectra were recorded on
a Shimadzu 8201 PC FTIR Spectrophotometer. 1H NMR spectra were
recorded on Bruker DRX 200 as well as Bruker DRX 300 spec-
trometer in deuterated solvents with TMS as internal reference.
Figure 3. Showing the arrangement of molecules in the unit cell.
The presence of spiro ring at C2 position in 6a enhances the de-
gree of non-planarity in the compound and thereby induces helicity,
by forcing the molecule to deviate from the most favorable planar
arrangement by bending out of the plane of the aromatic rings.

1462
R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
Mass spectra were recorded on JEOL SX-102 (FAB) spectrometer.
HRMS were recorded on JEOL JMS-600H (HRMS) spectrometer.
Melting points were determined on Bu¨chi-530 capillary melting
point apparatus and are uncorrected.
1208, 1136, 1006 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.62 (m, 2H,
CH2), 1.84–1.93 (m, 2H, CH2), 2.62–2.67 (m, 6H, CH2), 2.72–2.74 (m,
2H, CH2), 2.93 (t, J¼5.94 Hz, 2H, CH2), 3.01 (t, J¼6.78 Hz, 2H, CH2),
3.29 (br s, 4H, CH2), 3.58 (s, 2H, CH2), 7.24–7.39 (m, 8H, ArH), 7.54–
7.57 (m, 1H, ArH); 13C NMR (75 MHz, CDCl3): 21.11, 21.97, 24.13,
27.39, 28.28, 29.50, 49.63, 52.78, 62.02,107.23,116.91,124.35,125.77,
126.01, 126.53, 126.97, 127.47, 127.94, 130.51, 132.54, 133.92, 137.06,
139.07, 139.18, 139.31, 148.86; MS m/z 434 (Mþþ1); HRMS: (EI,
70 eV) calcd for C30H31N3 433.25180 (Mþ) found for m/z 433.25200.
4.2. General procedure for the synthesis of 6-sec-amino-
1,2,3,4,7,8-hexahydrobenzo[c]phenanthrenes (3a–d)
An equimolar mixture of 2-oxo-4-sec-amino-5,6-dihydro-2H-
benzo[h]chromene-3-carbonitriles, cyclohexanone and KOH in
DMF was stirred for 2–3 h. Completion of reaction was monitored
by TLC. Thereafter, reaction mixture was poured onto crushed ice
with vigorous stirring followed by neutralization with 10% HCl. The
precipitate obtained was filtered, washed with water, dried and
purified by neutral alumina column using 3% ethyl acetate in hex-
ane as eluent.
4.3. General procedure for the synthesis of 6-sec-amino-
1,2,7,8-tetrahydrobenzo[c]phenanthrene (3e–g)
These were prepared from the reaction of 2-oxo-4-sec-amino-
5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles and 2-cyclo-
hexenone and work-up as described in the earlier experiment. The
crude product was purified by neutral alumina column using 4%
ethyl acetate in hexane as eluent.
4.2.1. 6-(Piperidin-1-yl)-1,2,3,4,7,8-hexahydrobenzo[c]phenan-
threne-5-carbonitrile (3a). White powder; yield: 89%; mp: 156–
158 ꢀC; IR (KBr): 2926, 2855, 2368, 2213, 1596, 1461, 1351 cmꢁ1; 1H
4.3.1. 6-(Piperidin-1-yl)-1,2,7,8-tetrahydrobenzo[c]phenanthrene-5-
carbonitrile(3e). White powder; yield: 79%; mp: 162–164 ꢀC; IR
(KBr): 2957, 2362, 2203, 1584, 1417, 1352, 1300, 1209, 1105 cmꢁ1; 1H
NMR (300 MHz, CDCl3): d 1.62–1.70 (m, 8H, CH2), 1.84–1.93 (m, 2H,
CH2), 2.63–2.67 (m, 2H, CH2), 2.73–2.77 (m, 2H, CH2), 2.93 (t,
J¼5.97 Hz, 2H, CH2), 3.01 (t, J¼6.80 Hz, 2H, CH2), 3.21 (br s, 4H, CH2),
7.21–7.30 (m, 3H, ArH), 7.55–7.59 (m, 1H, ArH); 13C NMR (75 MHz,
NMR (300 MHz, CDCl3): d 1.64–1.72 (m, 6H, CH2), 2.32–2.39 (m, 2H,
CH2), 2.67–2.72 (m, 2H, CH2), 2.74–2.79 (m, 2H, CH2), 3.01 (t,
J¼8.05 Hz, 2H, CH2), 3.22 (br s, 3H, CH2 and CH), 3.90 (br s, 1H, CH),
6.09–6.15 (m, 1H, CH), 6.77–6.81 (m, 1H, CH), 7.25–7.29 (m, 3H,
ArH), 7.48–7.50 (m, 1H, ArH); 13C NMR (50 MHz, CDCl3): 21.75,
24.22, 24.86, 26.85, 27.01, 29.38, 52.26, 52.82,118.34, 124.76,125.80,
126.60, 127.29, 127.58, 127.89, 129.50, 133.28, 135.50, 137.52, 139.93,
140.81, 151.32; MS m/z 341 (Mþþ1); HRMS: (EI, 70 eV) calcd for
C24H24N2 340.19395 (Mþ) found for m/z 340.19403.
CDCl3): d 21.16, 22.01, 22.99, 23.82, 25.61, 27.33, 28.37, 29.50, 51.04,
106.56, 117.18, 124.28, 126.00, 126.43, 127.45, 130.01, 132.70, 134.00,
139.11, 139.20, 150.23; MS m/z 343 (Mþþ1); HRMS: (EI, 70 eV) calcd
for C24H26N2 342.20960 (Mþ) found for m/z 342.20941.
The crystal data of 3d: C30H31N3, M¼433.58, triclinic, P-1,
ꢀ
a¼10.219(6) Å,b¼11.256(9) Å,
c¼11.618(7) Å,
a
¼65.78(7)
,
,
b
¼81.96(6) ꢀ,
g
¼81.30(5)ꢀ, V¼1200.2(14) Å3, Z¼2, Dc¼1.200 gcmꢁ3
m
(Mo-K
a
)¼0.071 mmꢁ1, F(000)¼464, rectangular block, colorless,
size¼0.175ꢂ0.125ꢂ0.075 mm,
4868
reflections
measured
4.3.2. 6-(4-Methylpiperidin-1-yl)-1,2,7,8-tetrahydrobenzo[c]phenan-
threne-5-carbonitrile (3f). White powder; yield: 84%; mp: 130–
132 ꢀC; IR (KBr): 3018, 2934, 2363, 2222, 1655, 1560, 1429, 1217,
(Rint¼0.0414), 4109 unique, wR2¼0.2061 for all data, conventional
R¼0.0674 [( ¼000] on F-values of 1525 reflections with
I>2
D/s)
max
s
(I), S¼0.928 for all data and 299 parameters (deposit No: 3d:
1009 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
1.01 (d, J¼4.77 Hz, 3H,
759528).
CH3), 1.28–1.42 (m, 2H, CH2), 1.55–1.62 (m, 1H, CH), 1.69 (d,
J¼11.61 Hz, 2H, CH2), 2.31–2.39 (m, 2H, CH2), 2.71 (br s, 4H, CH2),
3.01 (t, J¼8.05 Hz, 2H, CH2), 3.13 (br s, 2H, CH2), 3.34 (br s, 2H, CH2),
6.08–6.15 (m, 1H, CH), 6.77–6.81 (m, 1H, CH), 7.24–7.29 (m, 3H,
ArH), 7.47–7.50 (m, 1H, ArH); 13C NMR (75 MHz, CDCl3): 20.50,
20.93, 25.76, 28.13, 28.42, 29.42, 33.93, 50.31, 124.55, 125.35,
125.70, 126.04, 126.31, 126.65, 128.25, 132.03, 134.20, 136.28,
138.68, 139.52, 149.90; MS m/z 355 (Mþþ1); HRMS: (EI, 70 eV)
calcd for C25H26N2 354.20960 (Mþ) found for m/z 354.20911.
4. 2.2. 6-(4-Methylpiperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-5-carbonitrile (3b). White powder; yield:
92%; mp: 150–152 ꢀC; IR (KBr): 2951, 2371, 2215, 1596, 1430, 1382,
1352, 1283, 1116, 1028 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.0 (d,
J¼6.12 Hz, 3H, CH3), 1.41–1.44 (m, 2H, CH2), 1.56–1.57 (m, 1H, CH),
1.61–1.40 (m, 4H, CH2),1.84–1.93 (m, 2H, CH2), 2.66 (d, J¼6.09 Hz, 2H,
CH2), 2.72 (br s, 2H, CH2), 2.93 (t, J¼5.95 Hz, 2H, CH2), 3.01 (t,
J¼6.80 Hz, 2H, CH2), 3.22 (br s, 2H, CH2), 3.33(br s, 2H, CH2), 7.22–7.31
(m, 3H, ArH), 7.55–7.59 (m,1H, ArH); MS m/z 357 (Mþþ1); HRMS: (EI,
70 eV) calcd for C25H28N2 356.22525 (Mþ) found for m/z 356.22541.
4.3.3. 6-(4-Benzylpiperazin-1-yl)-1,2,7,8-tetrahydrobenzo[c]phenan-
threne-5-carbonitrile (3g). White powder; yield: 87%; mp: 164–
166 ꢀC; IR (KBr): 2935, 2365, 2204, 1597, 1478, 1384, 1351, 1248,
4.2.3. 6-(4-Benzylpiperidin-1-yl)-1,2,3,4,7,8-hexahydro-
benzo[c]phenanthrene-5-carbonitrile (3c). White powder; Yield:
87%; mp: 148–150 ꢀC; IR (KBr): 2820, 2378, 2203, 1605, 1434, 1384,
1201 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 2.32–2.39 (m, 2H, CH2),
2.62 (br s, 4H, CH2), 2.67–2.78 (m, 4H, CH2), 3.01 (t, J¼8.04 Hz, 2H,
CH2), 3.31 (br s, 4H, CH2), 3.59 (s, 2H, CH2), 6.11–6.16 (m, 1H, CH),
6.77–6.81 (m, 1H, CH), 7.24–7.39 (m, 8H, ArH), 7.47–7.49 (m, 1H,
ArH); 13C NMR (75 MHz, CDCl3): 20.48, 23.86, 25.79, 28.05, 49.59,
52.75, 62.0, 116.81, 124.61, 125.28, 125.78, 126.05, 126.63, 126.74,
126.97, 127.93, 128.27, 131.87, 134.24, 138.56; MS m/z 432 (Mþþ1);
HRMS: (EI, 70 eV) calcd for C30H29N3 431.23615 (Mþ) found for m/z
431.23635.
1352, 1197, 1140 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.45–1.47 (m,
2H, CH2), 1.61–1.72 (m, 5H, CH and CH2), 1.83–1.92 (m, 2H, CH2),
2.60–2.66 (m, 4H, CH2), 2.72 (br s, 2H, CH2), 2.92 (t, J¼5.89 Hz, 2H,
CH2), 3.0 (t, J¼6.75 Hz, 2H, CH2), 3.12 (br s, 2H, CH2), 3.30 (br s, 2H,
CH2), 7.16–7.20 (m, 3H, ArH), 7.23–7.31 (m, 5H, ArH), 7.54–7.57 (m,
1H, ArH); 13C NMR (75 MHz, CDCl3): 21.33, 21.99, 27.32, 28.37,
29.48, 31.96, 36.64, 42.15, 50.28, 75.98, 117.09, 124.31, 124.56,
126.01, 126.47, 126.94, 127.47, 127.87, 130.19, 132.67, 134.04, 139.18,
139.36, 149.86; MS m/z 433 (Mþþ1); HRMS: (EI, 70 eV) calcd for
C31H32N2 432.25655 (Mþ) found for m/z 432.25617.
4.4. General procedure for the synthesis of protected
5-cyano-6-sec-amino-1,2,3,4,7,8-hexahydro-2-
oxobenzo[c]phenanthrene (6)
4. 2.4. 6-(4-Benzylpiperazin-1-yl)-1, 2, 3, 4, 7, 8-hexahy-
drobenzo[c]phenanthrene-5-carbonitrile (3d). White powder; yield:
95%; mp: 154–156 ꢀC; IR (KBr): 2931, 2363, 2214, 1595, 1436, 1351,
These were obtained by stirring an equimolar mixture of 2-oxo-
4-sec-amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles,
cyclohexan-1,4-dionemonoalkyleneketal and KOH in DMF for

R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
1463
1–2 h. After completion of reaction, excess of DMF was removed
under reduced pressure. The reaction mixture was poured onto
crushed ice with vigorous stirring. Neutralization with 10% HCl gave
a precipitate, which was filtered, washed with water, dried and
purified on neutral alumina column using 3% ethyl acetate in
hexane as eluent.
126.62, 126.93, 127.08, 127.86, 132.31, 134.80, 137.49, 139.31, 150.45;
MS m/z 491 (Mþþ1); HRMS: (EI, 70 eV) calcd for C33H34N2O2
490.26203 (Mþ) found for m/z 490.26213.
4.4.4. 5-Cyano-6-(4-benzylpiperazin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-ethylene ketal (6d). White pow-
der; yield: 81%; mp: 180–182 ꢀC; IR (KBr): 2923, 2373, 2210, 1595,
4. 4.1. 5-Cyano-6-(piperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-ethylene ketal (6a). White pow-
der; yield: 91%; mp: 216–218 ꢀC; IR (KBr): 2941, 2363, 2210, 1607,
1438, 1378, 1352, 1279, 1127 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
2.05 (t, J¼7.02 Hz, 2H, CH2), 2.61–2.66 (m, 6H, CH2), 2.71–2.73 (m,
2H, CH2), 3.16 (s, 2H, CH2), 3.21 (t, J¼7.05 Hz, 2H, CH2), 3.28 (br s,
4H, CH2), 3.58 (s, 2H, CH2), 3.87–3.92 (m, 2H, CH2), 3.93–3.99 (m,
2H, CH2), 7.22–7.38 (m, 8H, ArH), 7.48–7.51 (m, 1H, ArH); 13C NMR
(75 MHz, CDCl3): 24.16, 26.66, 28.15, 28.42, 29.61, 38.50, 49.59,
52.73, 61.99, 63.34, 106.70, 106.91, 116.76, 124.60, 125.79, 126.10,
126.69, 126.96, 127.10, 127.93, 132.19, 134.69, 136.98, 137.67, 139.18,
139.49, 149.43; MS m/z 492 (Mþþ1); HRMS: (EI, 70 eV) calcd for
C32H33N3O2 491.25728 (Mþ) found for m/z 491.25709.
1452, 1291, 1252, 1095 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.62–
1.70 (m, 6H, CH2), 2.05 (t, J¼7.04 Hz, 2H, CH2) 2.63–2.67 (m, 2H,
CH2), 2.71–2.74 (m, 2H, CH2), 3.16 (s, 2H, CH2), 3.21 (t, J¼6.94 Hz,
6H, CH2), 3.87–3.92 (m, 2H, CH2), 3.94–3.99 (m, 2H, CH2), 7.22–7.30
(m, 3H, ArH), 7.49–7.52 (m, 1H, ArH); 13C NMR (75 MHz, CDCl3):
d
22.97, 23.88, 25.57, 26.60, 28.24, 29.65, 38.47, 51.01, 63.33, 106.33,
106.03, 106.96, 117.03, 124.53, 126.08, 126.40, 126.59, 127.07, 132.36,
134.77, 137.48, 139.30, 139.48, 150.80; MS m/z 401 (Mþþ1); HRMS:
(EI, 70 eV) calcd for C26H28N2O2 400.21508 (Mþ) found for m/z
400.21493.
4. 4. 5. 5-Cyano-6-(piperidin-1-yl)-1, 2, 3, 4, 7, 8-hexahy-
drobenzo[c]phenanthrene-2-one-(2,2-dimethyltrimethylene)ketal
(6e). White powder; yield: 94%; mp: 238–240 ꢀC; IR (KBr): 2944,
The crystal data of 6a: C26H28N2O2, M¼400.50, monoclinic, P 2(1)/
n, a¼12.452(1) Å,b¼9.378(2) Å, c¼18.631(4) Å,
b
¼103.800(1)
,
,
2849, 2205, 1594, 1437, 1354, 1277, 1114, 1089 cmꢁ1 1H NMR
;
ꢀ
V¼2112.8(7) Å3, Z¼4, Dc¼1.259 gcmꢁ3
,
m
(Mo-K
a
)¼0.080 mmꢁ1
(300 MHz, CDCl3): d 0.83 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.65–1.70 (m,
F(000)¼856, rectangular block, yellow, size¼0.25ꢂ0.175ꢂ0.125 mm,
6H, CH2), 2.28 (t, J¼6.72 Hz, 2H, CH2), 2.64–2.74 (m, 4H, CH2), 3.08 (t,
J¼6.93 Hz, 2H, CH2), 3.21–3.24 (m, 6H, CH2), 3.37 (d, J¼11.58 Hz, 2H,
CH2), 3.63 (d, J¼11.49 Hz, 2H, CH2), 7.23–7.31 (m, 3H, ArH), 7.52–7.57
(m, 1H, ArH); 13C NMR (75 MHz, CDCl3): 21.00, 21.56, 22.96, 23.84,
24.0, 25.57, 25.76, 28.23, 28.90, 39.43, 51.0, 69.19, 96.33, 105.86,
117.13, 124.61, 125.78, 126.06, 126.57, 127.11, 132.37, 134.75, 137.72,
139.26,139.44,150.62; MS m/z 443 (Mþþ1); HRMS: (EI, 70 eV) calcd
for C29H34N2O2 442.26203 (Mþ) found for m/z 442.26188.
4843 reflections measured (Rint¼0.0387), 3723 unique, wR2¼0.1564
for all data, conventional R¼0.0527 [(
D
/
s
)
¼000] on F-values of
max
1534 reflections with I>2
s
(I), S¼0.964 for all data and 272
parameters.
Unit cell determination and intensity data collection (2
q
¼50ꢀ)
was performed on a Bruker P4 diffractometer at 293(2) K. Structure
solutions by direct methods and refinements by full-matrix least-
squares methods on F2. Programs: XSCANS [Siemens Analytical
X-ray Instrument Inc.: Madison, Wisconsin, USA 1996], SHELXTL-
NT [Bruker AXS Inc.: Madison, Wisconsin, USA 1997], MERCURY
[Version 1.4.1, Cambridge Crystallographic Data Center, 12 Union
Road, Cambridge, CB2 1EZ, U. K]. CCDC (deposit No: 6a: 759529)
contains the supplementary crystallographic data. These data can
be obtained free of charge from www.ccdc.cam.uk/conts/retrie-
ving.html [or from the Cambridge Crystallographic Data Center, 12
Union Road, Cambridge, CB2 1EZ, U. K; Fax: (internat.) þ44 1223/
336 033; E-mail: deposit@ccdc.cam.ac.uk.
4.4.6. 5-Cyano-6-(4-benzylpiperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-(2,2-dimethyltrimethylene)ketal
(6f). White powder; yield: 89%; mp: 230–232 ꢀC; IR (KBr): 3031,
2861, 2219, 1253, 1209, 1156, 1021, 1000, 954, 761 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
d 0.83 (s, 3H, CH3), 0.97 (s, 3H, CH3), 1.02 (d,
J¼4.81 Hz, 3H, CH3), 1.29–1.47 (m, 2H, CH2), 1.50–1.61 (m, 1H, CH),
1.68 (d, J¼11.70 Hz, 2H, CH2), 2.27 (t, J¼6.78 Hz, 2H, CH2), 2.67–2.70
(m, 4H, CH2), 3.08 (t, J¼6.84 Hz, 4H, CH2), 3.23 (s, 2H, CH2), 3.31 (br
s, 2H, CH2), 3.37 (d, J¼11.22 Hz, 2H, CH2), 3.63 (d, J¼11.49 Hz, 2H,
CH2), 7.22–7.30 (m, 3H, ArH), 7.52–7.55 (m, 1H, ArH); 13C NMR
(75 MHz, CDCl3): 20.90, 21.01, 21.56, 24.12, 25.77, 28.24, 28.89,
29.41, 33.95, 39.36, 50.29, 69.19, 96.35, 117.09, 124.60, 125.81,
126.06, 126.56, 127.12, 132.39, 134.75, 137.78, 139.25, 139.44, 150.41;
MS m/z 533 (Mþþ1); HRMS: (EI, 70 eV) calcd for C30H36N2O2
456.27768 (Mþ) found for m/z 456.27770.
4.4.2. 5-Cyano-6-(4-methylpiperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-ethylene ketal (6b). White pow-
der; yield: 94%; mp: 220–222 ꢀC; IR (KBr): 2919, 2362, 2208, 1592,
1522, 1477, 1351, 1194 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.0 (d,
J¼6.21 Hz, 3H, CH3), 1.34–1.41 (m, 2H, CH2), 1.50–1.55 (m, 1H, CH),
1.68 (d, J¼11.82 Hz, 2H, CH2), 2.05 (t, J¼7.0 Hz, 2H, CH2), 2.65–2.71
(m, 4H, CH2), 3.16–3.24 (m, 6H, CH2), 3.31 (br s, 2H, CH2), 3.87–3.92
(m, 2H, CH2), 3.94–3.99 (m, 2H, CH2), 7.24–7.31 (m, 3H, ArH), 7.49–
7.53 (m, 1H, ArH); 13C NMR (75 MHz, CDCl3): 20.90, 26.60, 28.24,
29.41, 29.64, 33.94, 38.47, 50.30, 63.32, 106.96, 117.02, 124.53,
126.07, 126.36, 126.58, 127.07, 132.37, 134.75, 137.48, 139.38, 150.63;
MS m/z 415 (Mþþ1); HRMS: (EI, 70 eV) calcd for C27H30N2O2
414.23073 (Mþ) found for m/z 414.23091.
4.4.7. 5-Cyano-6-(4-benzylpiperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-(2,2-dimethyltrimethylene)ketal
(6g). White powder; yield: 91%; mp: 182–184 ꢀC; IR (KBr): 2949,
2872, 2371, 2215, 1596, 1429, 1283, 1209, 1116, 1068, 1029, 936,
749 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 0.83 (s, 3H, CH3),1.02 (s, 3H,
CH3), 1.42–1.45 (m, 1H, CH), 1.56 (s, 2H, CH2), 1.70 (d, J¼10.53 Hz,
3H, CH and CH2), 2.26 (t, J¼6.76 Hz, 2H, CH2), 2.61 (d, J¼6.66 Hz, 2H,
CH2), 2.67 (br s, 4H, CH2), 3.07 (t, J¼6.84 Hz, 4H, CH2), 3.22 (br s, 4H,
CH2), 3.36 (d, J¼11.46 Hz, 2H, CH2), 3.62 (d, J¼11.43 Hz, 2H, CH2),
7.16–7.20 (m, 3H, ArH), 7.24–7.31 (m, 5H, ArH), 7.53–7.55 (m, 1H,
ArH); 13C NMR (50 MHz, CDCl3): 22.21, 22.77, 25.20, 26.98, 29.42,
30.09, 33.11, 37.84, 40.67, 43.33, 51.45, 70.34, 97.51, 118.23, 125.76,
125.84, 127.29, 127.81, 128.13, 128.33, 127.05, 133.53, 135.97, 138.99,
140.49, 140.64, 151.43; MS m/z 533 (Mþþ1); HRMS: (EI, 70 eV) calcd
for C36H40N2O2 532.30898 (Mþ) found for m/z 532.30909.
4.4.3. 5-Cyano-6-(4-benzylpiperidin-1-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-ethylene ketal (6c). White powder;
yield: 89%; mp: 146–148 ꢀC; IR (KBr): 2928, 2363, 2216, 1596, 1458,
1354, 1119, 1060 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 1.45 (br s, 1H,
CH), 1.60 (br s, 1H, CH), 1.70 (d, J¼10.38 Hz, 3H, CH and CH2), 2.05 (t,
J¼7.04 Hz, 2H, CH2), 2.61 (d, J¼6.66 Hz, 2H, CH2), 2.65–2.70 (m, 4H,
CH2), 3.16–3.24 (m, 8H, CH2), 3.87–3.92 (m, 2H, CH2), 3.94–3.96 (m,
2H, CH2) 7.16–7.23 (m, 3H, ArH), 7.24–7.31 (m, 5H, ArH), 7.48–7.51
(m, 1H, ArH); 13C NMR (75 MHz, CDCl3): 26.61, 28.21, 29.61, 31.90,
36.64, 38.49, 42.13, 50.26. 63.34, 106.93, 117.50, 124.56, 126.09,
4.4.8. 5-Cyano-6-(tetrahydroisoquinolin-2-yl)-1,2,3,4,7,8-hexahy-
drobenzo[c]phenanthrene-2-one-(2,2-dimethyltrimethylene)ketal

1464
R. Pratap et al. / Tetrahedron 66 (2010) 1458–1464
(6h). White powder; yield: 99%; mp: 170–172 ꢀC; IR (KBr): 2820,
2734, 2210, 1595, 1437, 1382, 1352 cmꢁ1 1H NMR (300 MHz,
CDCl3): 0.84 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.55 (s, 2H, CH2), 2.30
(br s, 2H, CH2), 2.62 (t, J¼6.30 Hz, 2H, CH2), 2.74 (br s, 2H, CH2),
2.95–3.01 (m, 2H, CH2), 3.12 (t, J¼6.90 Hz, 2H, CH2), 3.27 (s, 2H,
CH2), 3.39 (d, J¼11.52 Hz, 2H, CH2), 3.64 (d, J¼11.52 Hz, 2H, CH2),
4.35 (s, 2H, CH2), 7.0–7.03 (m,1H, ArH), 7.13–7.18 (m, 3H, ArH), 7.24–
7.29 (m, 3H, ArH), 7.56–7.60 (m, 1H, ArH); 13C NMR (50 MHz,
(t, J¼6.67 Hz, 2H, CH2), 2.63 (d, J¼6.66 Hz, 2H, CH2), 2.69 (d,
J¼5.10 Hz, 2H, CH2), 2.74 (br s, 2H, CH2), 3.14–3.22 (m, 2H, CH2),
3.35 (t, J¼6.63 Hz, 4H, CH2), 3.88 (s, 2H, CH2), 7.17–7.22 (m, 3H,
;
d
ArH), 7.27–7.32 (m, 6H, ArH); 13C NMR (50 MHz, CDCl3):
d 26.97,
29.28, 33.09, 36.43, 37.81, 43.31, 44.50, 51.59, 125.70, 125.83, 126.06,
127.52, 128.52, 128.18, 128.31, 128.51, 132.70, 140.03, 140.43, 140.78,
151.51, 209.59; MS m/z 447 (Mþþ1); HRMS: (EI, 70 eV) calcd for
C31H30N2O 446.23581 (Mþ) found for m/z 446.23564.
CDCl3): d 22.15, 22.71, 24.82, 25.14, 26.94, 29.24, 30.03, 30.46, 40.64,
48.66, 52.70, 70.32, 97.42, 107.56, 117.89, 125.50, 125.80, 125.97,
127.32, 127.88, 127.93, 128.29, 129.08, 133.34, 134.43, 134.68, 136.50,
139.28, 140.48, 140.76, 150.13; MS m/z 491 (Mþþ1); HRMS: (EI,
70 eV) calcd for C33H34N2O2 490.26203 (Mþ) found for m/z
490.26189.
Acknowledgements
VJR, RP, RR thank CSIR, New Delhi for their financial assistance.
They are also thankful to SAIF, CDRI, Lucknow for providing spec-
troscopic data. VPG is thankful to CSIR and AICTE, New Delhi, India
for supporting this work through major research projects.
4.5. General Procedure for the synthesis of 2-oxo-6-sec-
amino-1,2,3,4,7,8-hexahydrobenzo[c]phenanthrene-3-
carbonitriles (7)
References and notes
1. Cheung, J.; Field, L. D.; Regalia, F.; Sternhell, S. Aust. J. Chem. 1995, 48, 1707–1725.
2. (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Chemistry and Carcinige-
nicity Cambridge University Press: Cambridge, UK, 1991, Chapter 3; (b). Ste-
venson, J. L.; Von Haam, E. Am. Ind. Hyg. Assoc. J. 1965, 26, 475.
3. Lunde, G.; Bjorseth, A. Nature (London) 1977, 268, 518.
4. (a) Wood, A. W.; Chang, R. L.; Levin, W.; Ryan, D. E.; Thomas, P. E.; Croisy-
Delcey, M.; Ittah, Y.; Yagi, H.; Jerina, D. M.; Conney, A. H. Cancer Res. 1980, 40,
2876; (b). Harvey, R. G. Acc. Chem. Res. 1981, 14, 218.
5. (a) Dipple, A.; Pigott, M. A.; Agrawal, S. K.; Yagi, H.; Sayer, J. M.; Jerina, D. M.
Nature 1987, 327, 535; (b). Agarwal, S. K.; Jane, M.; Yeh, H. J. C.; Pannell, L. K.;
Hilton, B. D.; Pigott, M. A.; Dipple, A.; Yagi, H.; Jerina, D. M. J. Am. Chem. Soc.
1987, 109, 2497.
6. (a) Pullman, A. Ann. Chim. 1947, 2, 5; (b). Badger, G. M. Br. J. Cancer 1948, 2, 309.
7. (a) Newman, M. S.; Anderson, H. V.; Takemura, K. H. J. Am. Chem. Soc. 1953, 75,
347; (b). Djerassi, C.; Grossnickle, T. T. J. Am. Chem. Soc. 1954, 76, 1741; (c). Wilds,
A. L.; Werth, R. G. J. Org. Chem. 1952, 17, 1154; (d). Mukhergi, S. M.; Gaind, V. S.;
Rao, P. N. J. Org. Chem. 1957, 19, 328; (e). Tatevosyan, G. T.; Babayan, V. O. J. Gen.
Chem. 1952, 22, 1421.
8. (a) Bergmann, E. D.; Pelchowicz, Z. J. Org. Chem. 1954, 19, 1383; (b). Newman,
M. S.; Wolf, M. J. Am. Chem. Soc. 1952, 74, 3225; (c). Newman, M. S.; Wise, R. M.
J. Am. Chem. Soc. 1956, 78, 450; (d). Newman, M. S.; Lednicer, D. J. Am. Chem. Soc.
1956, 78, 4765; (e). Newman, M. S.; Philips, D. J. Am. Chem. Soc. 1959, 81, 3667;
(f). Newman, M. S.; Boden, H. J. Org. Chem. 1961, 26, 1759; (g). Newman, M. S.;
Bium, J. J. Am. Chem. Soc. 1964, 86, 503.
9. Phillips, D. D.; Johnson, A. W. J. Am. Chem. Soc. 1955, 77, 5977.
10. Reddy, M. P.; Rao, G. S. K. J. Organomet. Chem. 1981, 46, 5371.
11. Pataki, J.; Harvey, R. G. J. Org. Chem. 1982, 47, 20.
These were obtain through deprotection of ketal by stirring in
80% formic acid for 1 h at room temperature. After completion of
the reaction, excess of formic acid was removed and reaction
mixture was poured onto ice cold water. The precipitate obtained
was filtered washed with water and purified by crystallization with
1:1 chloroform and methanol.
4.5.1. 2-Oxo-6-(piperidin-1-yl)-1,2,3,4,7,8-hexahydro-
benzo[c]phenanthrene-5-carbonitrile (7a). White powder; yield:
97%; mp: 198–200 ꢀC; IR (KBr): 2926, 2821, 2372, 2213, 1716, 1595,
1435, 1383, 1351, 1282, 1232, 1199, 1025 cmꢁ1 1H NMR (300 MHz,
;
CDCl3):
d
1.66–1.73 (m, 6H, CH2), 2.53 (t, J¼6.60, 2H, CH2), 2.68–2.70
(m, 2H, CH2), 2.76–2.78 (m, 2H, CH2), 3.24 (br s, 4H, CH2), 3.36 (t,
J¼6.60 Hz, 2H, CH2), 3.88 (s, 2H, CH2), 7.26–7.29 (m, 4H, ArH); 13C
NMR (75 MHz, CDCl3):
d 22.89, 23.85, 25.54, 25.76, 28.08, 35.24,
43.27, 51.11, 105.18, 116.83, 124.31, 124.82, 126.28, 127.06, 127.28,
131.52, 135.22, 138.95, 139.52, 150.66, 208.44; MS m/z 357 (Mþþ1);
HRMS: (EI, 70 eV) calcd for C24H24N2O 356.18886 (Mþ) found for
m/z 356.18897.
4.5.2. 6-(4-Benzylpiperidin-1-yl)-2-oxo-1,2,3,4,7,8-hexahydro-
benzo[c]phenanthrene-5-carbonitrile (7b). White powder; Yield:
97%; mp: 140–142 ꢀC; IR (KBr): 2927, 2826, 2365, 2214, 1718, 1594,
1436, 1382, 1350, 1231, 1116, 1028 cmꢁ1; 1H NMR (300 MHz, CDCl3):
12. Sayed, M. A.; Abd-El-Halim, M. S.; Hataba, A. M. Egyptian J. Chem. 1989, 32, 547.
13. Chowdhury, S.; Zhao, B.; Srieckus, V. Polycycl. Aromat. Compd. 1994, 5, 27.
14. Mishra, V.; Amin, S. J. Org. Chem. 1990, 55, 4478.
15. Kumar, S. J. Org. Chem. 1997, 62, 8535.
16. Pratap, R.; Ram, V. J. Tetrahedron Lett. 2007, 48, 2755.
d
1.54–1.57 (m, 2H, CH2), 1.73 (d, J¼10.23 Hz, 3H, CH and CH2), 2.52
17. Gompper, R.; Topfl, W. Chem. Ber. 1962, 95, 2861.