Ceric Ammonium Nitrate (CAN)-Catalyzed, Efficient, One-Pot, Three-Component, aza-Diels-Alder Reactions for a Facile Synthesis of Tetrahydropyranoquinoline Derivatives

Article abstract of DOI:10.1080/00397911.2014.956366

A simple, efficient, and cost-effective method for the synthesis of tetrahydropyranoquinoline derivatives by a one-pot condensation of aromatic aldehyde, aromatic amine, and 3,4-dihydro-2H-pyran respectively in the presence of ceric ammonium nitrate (CAN)

Full text of DOI:10.1080/00397911.2014.956366

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Ceric Ammonium Nitrate (CAN) Catalyzed Efficient
One-Pot Three Component Aza-Diels-Alder Reactions
for a Facile Synthesis of Tetrahydropyranoquinoline
Derivatives
a
a
a
Ravinder Goud Puligoundla , Hanmanth Reddy Vulupala , Nagaiah Kommu & Sudhakar Babu
b
Kondra
a
Organic and Biomolecular Chemistry Division, Indian Institute of Chemical Technology
Hyderabad, India
b
Department of Chemistry, Sri Krishnadevaraya University-Ananthapur, India
Accepted author version posted online: 03 Nov 2014.
To cite this article: Ravinder Goud Puligoundla, Hanmanth Reddy Vulupala, Nagaiah Kommu & Sudhakar Babu Kondra (2014):
Ceric Ammonium Nitrate (CAN) Catalyzed Efficient One-Pot Three Component Aza-Diels-Alder Reactions for a Facile Synthesis
of Tetrahydropyranoquinoline Derivatives, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.956366
To link to this article: http://dx.doi.org/10.1080/00397911.2014.956366
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Ceric Ammonium Nitrate (CAN) catalyzed efficient one-pot three component aza-
Diels-Alder reactions for a facile synthesis of tetrahydropyranoquinoline derivatives
1
1
1
Ravinder Goud Puligoundla , Hanmanth Reddy Vulupala , Nagaiah Kommu , Sudhakar
2
Babu Kondra
1
Organic and Biomolecular Chemistry Division, Indian Institute of Chemical Technology
Hyderabad, India,
2
Department of Chemistry, Sri Krishnadevaraya University-Ananthapur, India
Department of Chemistry, Sri Krishnadevaraya University-Ananthapur, 515 0037 India.
E-mail: mailto: drksbabu@gmail.com
Abstract
A simple, efficient and cost-effective method for the synthesis of
tetrahydropyranoquinoline derivatives by a one-pot condensation of aromatic aldehyde,
aromatic amine and 3,4-dihydro-2H-pyran respectively in the presence of ceric
ammonium nitrate (CAN) has been described.
KEYWORDS: Multicomponent reactions, tetrahydropyranoquinolines, 3,4-dihydro-2H-
pyran
1
. INTRODUCTION
In recent years, the multi-component reactions are highly important because of their wide
range of applications in pharmaceutical chemistry for the rapid generation of structural
1

[
1-3]
diversity in combinatorial libraries for drug discovery.
MCRs are extremely
convergent, producing a remarkably high increase of molecular complexity in just one
step. Recently Tetrahydroquinoline derivatives has attained considerable significance
important class of natural products and exhibit biological activities in various fields, such
[
4-7]
as psychotropic, antiallergic, antiinflamatory and estronegic
and Pyrano
[
8-10]
tetrahydroquinolines are found in several alkaloids
such as Simulenoline 1,
huajiaosimuline 2, zanthodioline 3, flindersine 4, veprisine 5 and oricine 6 (Figure 1).
Due to their broad spectrum of biological interest chemists have developed methods for
[11-12]
the synthesis of tetrahydroquinolines.
Ceric (IV) ammonium nitrate (CAN) is a convenient and widely used reagent for
affecting a wide array of synthetic transformations due to its many advantages such as
solubility in organic solvents, low toxicity, high reactivity, and ease of handling.
Although Ce (IV) derivatives are generally employed as one electron oxidants, the use of
[
13]
CAN as Lewis acid in C–C bond forming reaction has attracted great deal of attention.
In continuation of our ongoing research for the development of simple and efficient
[
14-18]
methods for the synthesis of various heterocyclic compounds
here, we present a
simple, mild and efficient protocol for synthesis of tetrahydropyranoquinoline derivatives
using CAN catalyst.
[
19-31]
So far a very few methods have been reported
for the synthesis of
tetrahydropyranoquinoline derivatives However, some of the methods employed for these
synthesis have some limitations. To avoid these limitations we have searched for a new
CAN catalyst, with high catalytic activity, easy availability, short reaction time and
2

simple work-up. CAN attraced our attention, since it has been used in many organic
transformations.
2
. RESULTS AND DISCUSSION
To the best of our knowledge, in literature there appears no report for the synthesis and
screening of tetrahydropyranoquinoline derivatives using CAN. This fact has prompted
us to investigate in depth the utility of CAN for the synthesis of
tetrahydropyranoquinolines derivatives by a one-pot condensation of aryl aldehydes,
substituted anilines, and 3,4-dihydro-2H-pyran in acetonitrile at room temperature
(
Scheme 1).
Initially, a pilot reaction was attempted using using benzaldehyde (2 mmol), aniline (2.2
mmol) and 3,4-dihydro-2H-pyran (2.6 mmol) in the presence of CAN (46 mg, 0.2 mmol)
without any solvent. After 4 h, only 27 % of a mixture of the C-2 epimers (4 and 5) of a
tetrahydroquinoline product was isolated as 1:1 ratio. This reaction (10 h) resulted in the
isolation of the required product namely 5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinolines (4a) and (5a) in low yield (45%). Increasing the amount of CAN
to one mol equivalent did not improve the product yield to a considerable amount.
Subsequently, we investigated on the use of different catalysts and solvents for the
purpose. In chlorinated solvents such as dichloromethane and chloroform the reaction
was very slow and resulted in lower product yield. Similar results were obtained in
coordinating solvents such as THF, diethyl- and dimethyl ether and protic solvents such
as MeOH or EtOH. After screening different solvents, CH CN came out as the solvent of
3
3

choice, which not only afforded the products in good yield, but also with higher reaction
rates (90% yield in 0.5 h). It is also noticed that the condensation using CAN proceeds
rapidly and is superior to the different reagents with respect to reaction time, temperature
and yield. This claim is justified through the representative examples, illustrated in
1
Scheme 1. All the reactions were characterized by H NMR, IR and mass spectrometry.
In order to extend the scope of this catalytic transformation and find general applicability
of this method, a reaction between aromatic aldehydes (1) and aniline (2) with 3,4-
dihydro-2H-pyran (3) was verified. No observable ortho- and para- substituent effect was
noted for various anilines used in the reaction (entry 4k). This was one of the draw backs
of the earlier methods. Aromatic aldehydes 1a-l, aniline 2 and 3,4-dihydro-2H-pyran 3 in
the presence of CAN undergo a fast 1:1:1 addition reaction at room temperature in
acetonitrile (0.5-1 h) to produce substituted 5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinolines (4a) and (5a) derivatives 4a-l (Scheme 1). The results were
excellent in terms of yields and product purity and compounds 4a-l, 5a-l are stable solids
1
13
whose structures are fully supported by IR, H NMR, C NMR and mass spectrometry
analysis.
In summary, we have developed an economically and environmentally friendly procedure
for the synthesis of tetrahydropyranoquinoline derivatives with excellent yields and short
reaction times which involve the use of inexpensive catalyst CAN under acetonitrile
conditions. Furthermore, the present procedure is readily amenable to parallel synthesis
and generation of combinatorial tetrahydropyranoquinoline libraries.
4

In order to extend the scope of this catalytic transformation, the general applicability of
this method was verified by reacting with the number of substituted benzaldehydes,
substituted anilines and different dienophiles. 2-Cyclohexenone (6) was utilized to obtain
the corresponding phenanthridinone derivatives (7 m-n) and (8 m-n) (70:30) in 79.2%
yield (Scheme 2).
[
32]
Phenanthridine skeletons are present in lycorine, chelidonine and
haemanthamine alkaloids. CAN also catalyzed effectively the imino Diels-Alder reaction
of in situ generated N-benzylidene-1-napthylamine (9) with 3, 4-dihydro-2H-pyran and
2
,3-dihydrofuran to afford the phenanthridine derivatives (10) and (11) as a mixture of cis
and trans isomers in good overall yields (65%) (Scheme 3). The pyran ring was cis-fused
in the tetrahydroquinoline moiety and the stereochemistry of the products was established
based on the coupling constants. The coupling constant of C5-H (J4a, 5 = 4.6-5.5 Hz) in 4
indicated the cis relationship between C-4a and C-5, whereas in 5 (J4a, 5 = 10.2-11.10 Hz)
trans form. The simplicity, together with the use of inexpensive, non-toxic and
environmentally benign nature of CAN catalyst in CH
3
CN solvent is a remarkable feature
of the procedure.
3
. CONCLUSION
In summary, we have developed an economically and environmentally friendly procedure
for the synthesis of tetrahydropyranoquinoline phenanthridinone, phenanthridine
derivatives with excellent yields and short reaction times which involve the use of
5

inexpensive catalyst CAN under acetonitrile conditions. Furthermore, the present
procedure is readily amenable to parallel synthesis and generation of combinatorial
tetrahydropyranoquinoline libraries.
4
. EXPERIMENTAL
4
.1 Materials And Methods
All the commercial reagents and solvents were used without further purification
unless otherwise stated. Melting points were recorded on a Buchi 535 melting point
apparatus and are uncorrected. All the reactions were monitored by thin layer
chromatography performed on precoated silica gel 60F254 plates (Merck). Compounds
were visualized with UV light at 254 nm and 365 nm, I
2
and heating plates after dipping
in 2% phosphomolybdic acid in 15% aq. H SO soln. IR spectra were recorded on a
2
4
Perkin-Elmer 683 or a 1310 FT-IR spectrometers with KBr pellets. NMR spectra were
recorded on a Varian Unity-400 MHz and BRUKER AMX 300 spectrometers using TMS
1
3
as an internal standard. C NMR was recorded on a Varian Unity 100 MHz using CDCl
as internal standard. Mass spectra were recorded on a VG Micromass 7070H and a
Finnigan Mat 1020B mass spectrometers operating at 70eV.
3
Typical experimental procedure for the preparation of compounds
tetrahyroquinolines: Benzaldehye (1.1 mmol), Aniline (1.1 mmol), 3,4-dihydro-2H-
pyran (1.3 mmol) and in acetonitrile (5 mL) were mixed in a flask and CAN (10 mol %)
was added at room temperature. The resulting mixture was stirred at room temperature
6

for 30 min and completion of the reaction was monitored by TLC (ethyl acetate: hexane
:6). The reaction mixture was extracted into CHCl and dried over Na SO and solvent
was evaporated and the crude residue obtained was purified by column chromatography
silica gel, ethyl acetate-hexane 10:90] to give pure tetrahydropyranoquinolines 4 and 5
in 97 % yield.
4
3
2
4
[
5
5
3
1
1
-(3-Methoxy-phenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (4 &
-
1
b): Cis isomer : Thick syrup; Rf (20% EtOAc/n-hexane) 0.5.; IR (KBr) (νmax, cm ):
1
374 (N-H), 3040, 2923, 2855, 1515, 1345, 1068, 759; H NMR (300 MHz,CDCl
3
), :
.31-1.68 (m, 4H), 2.09-2.18 (m, 1H); 3.67 (m, 1H), 3.81 (s, 3H), 4.64 (d, J = 2.2 Hz,
H), 5.27 (d, J = 5.2 Hz, 1H), 6.54 (d, J = 8.3 Hz, 1H), 6.78 (t, J = 11.3 Hz, 1H), 7.04 (t,
+
J = 7.5 Hz, 3H), 7.24 (d, J = 7.5 Hz, 1H), 7.37 (d, 1H); MS (ESI) m/z 296 ([M+H]) .
Anal. Calcd. for C19
.17; N, 4.75.
H
21NO : C, 77.26; H, 7.17; N, 4.74; O, 10.83. Found: C, 77.23; H,
2
7
o
-1
Trans isomer : Mp 99-100 C; Rf (20% EtOAc/n-hexane) 0.48.; IR (KBr) (νmax, cm ):
1
3
1
374 (N-H), 3040, 2923, 2855, 1515, 1345, 1068, 759; H NMR (300 MHz, CDCl
3
), :
.37-1.55 (m, 4H), 2.09-2.21 (m, 1H), 3.69 (dt, J = 3.0, 9.8 Hz, 1H), 3.79 (s, 3H), 4.09
(
dd, J = 3.7, 11.3 Hz, 1H), 4.34 (d, J = 2.2 Hz, 1H), 4.67 (d, J = 10.5 Hz, 1H), 6.48 (d, J
7.5 Hz, 1H), 6.65 (t, J = 8.3 Hz, 1H), 6.81 (dd, J = 3.7, 8.3 Hz, 1H), 6.94 (d, J = 8.3 Hz,
=
2
H), 7.04 (dt, J = 1.51, 7.5 Hz, 1H), 7.16 (dd, J = 1.5, 7.5 Hz, 1H), 7.24 (dd, J = 1.5, 7.5
+
Hz, 1H); MS (ESI) m/z 296 ([M+H]) . Anal. Calcd. for C19
H
21NO : C, 77.26; H, 7.17; N,
2
4
.74; O, 10.83. Found: C, 77.25; H, 7.18; N, 4.74.
7

5
5
3
1
1
6
7
6
-(2,4-Dichloro-phenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (4 &
o
-1
e): Cis isomer; Mp 133-136 C; Rf (20% EtOAc/n-hexane) 0.5.; IR (KBr) (νmax, cm ):
1
374 (N-H), 3040, 2923, 2855, 1515, 1345, 1068, 759; H NMR (300 MHz, CDCl
3
), :
.39-1.57 (m, 4H), 2.18-2.38 (m, 1H), 3.42 (dt, J = 3.0, 11.3 Hz, 1H), 3.58 (dd, J = 3.7,
1.3 Hz, 1H), 5.01 (d, J = 2.2 Hz, 1H), 5.26 (d, J = 5.2 Hz, 1H), 6.55 (d, J = 6.8 Hz, 1H),
.77 (t, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 7.27 (d, J = 8.3 Hz, 1H), 7.64 (m, 2H),
+
.62 (d, J = 8.3 Hz, 2H); MS (ESI) m/z 334 ([M+H]) . Anal. Calcd. for C18
H
17Cl NO: C,
2
4.68; H, 5.13; Cl, 21.21; N, 4.19; O, 4.79. Found: C, 64.66; H, 5.14; N, 4.18.
-1
Trans isomer : Thick syrup; Rf (20% EtOAc/n-hexane) 0.45.; IR (KBr) (νmax, cm ): 3374
1
(
N-H), 3040, 2923, 2855, 1515, 1345, 1068, 759; H NMR (300 MHz, CDCl
3
), : 1.39-
1
.57 (m, 4H), 2.18-2.38 (m, 1H), 3.63 (dt, J = 3.0, 11.3 Hz, 1H), 3.92 (dd, J = 3.7, 11.3
Hz, 1H), 4.37 (d, J = 3.7 Hz, 1H), 5.09 (d, J = 8.3 Hz, 1H), 6.49 (d, J = 6.8 Hz, 1H), 6.69
(
t, J = 7.5 Hz, 1H), 7.05 (t, J = 8.3 Hz, 1H), 7.24 (m, 3H), 7.39-7.45 (m, 2H); MS (ESI)
+
m/z 334 ([M+H]) . Anal. Calcd. for C18
H
17Cl NO: C, 64.68; H, 5.13; Cl, 21.21; N, 4.19;
2
O, 4.79. Found: C, 64.68; H, 5.12; N, 4.20
5
-(4-Nitro-phenyl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (4 & 5q):
.
o
-1
Cis isomer; Mp 163-165 C; Rf (20% EtOAc/n-hexane) 0.5.; IR (KBr) (νmax, cm ): 3374
1
(
N-H), 3040, 2923, 2855, 1515, 1345, 1068, 759 ; H NMR (300 MHz, CDCl
3
), : 1.17-
1
.59 (m, 4H), 2.16-2.24 (m, 1H), 3.41 (dt, J = 2.9, 9.5 Hz, 1H), 3.61 (dd, J = 3.2, 11.9
Hz, 1H), 3.81 (s, 1H), 4.68 (d, J = 2.2 Hz, 1H), 5.31 (d, J = 5.8 Hz, 1H), 6.61 (d, J = 8.1
8

Hz, 1H), 6.81 (t, J = 7.3 Hz, 1H), 7.07 (t, J = 7.3 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.64
+
(
d, J = 8.8 Hz, 2H), 8.26 (d, J = 8.8 Hz, 2H); MS (ESI) m/z 311 ([M+H]) . Anal. Calcd.
for C18
H
18
N
2
3
O : C, 69.66; H, 5.85; N, 9.03; O, 15.47. Found: C, 69.64; H, 5.84; N, 9.00.
o
-1
Trans isomer : Mp 136-137 C; Rf (20% EtOAc/n-hexane) 0.45.; IR (KBr) (νmax, cm ):
1
3
1
377 (N-H), 3070, 2929, 2852, 1517, 1344, 1080, 750; H NMR (300 MHz, CDCl
3
), :
.20-1.49 (m, 4H), 2.11-2.22 (m, 1H), 3.44 (dt, J = 2.9, 9.5 Hz, 1H), 3.77 (dd, J = 3.2, 1.9
Hz, 1H), 4.04 (s, 1H), 4.39 (d, J = 2.9 Hz, 1H), 4.85 (d, J = 10.2 Hz, 1H), 6.56 (d, J = 7.3
Hz, 1H), 6.74 (t, J = 7.3 Hz, 1H), 7.11 (t, J = 7.3 Hz, 1H), 7.23 (d, J = 8.8 Hz, 1H), 7.64
+
(
d, J = 8.8 Hz, 2H), 8.26 (d, J = 8.8 Hz, 2H); MS (ESI) m/z 311 ([M+H]) . Anal. Calcd.
for C18
H
18
N
2
3
O : C, 69.66; H, 5.85; N, 9.03; O, 15.47. Found: C, 69.66; H, 5.84; N, 9.01.
5
-(4-Bromo-phenyl)-9-isopropyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-]quinoline
o
-
(
4 & 5i): Cis isomer :Mp 101-104 C; Rf (20% EtOAc/n-hexane) 0.5.; IR (KBr) (νmax, cm
1
1
)
: 3368 (N-H), 2936, 2860, 1493, 1067, 818; H NMR (300 MHz, CDCl
3
), : 1.21 (s,
3
2
5
7
H), 1.25 (s, 3H), 1.42-1.59 (m, 2H), 2.02-2.13 (m, 1H), 2.74-2.88 (m, 1H), 3.32 (dt, J =
.9, 10.9 Hz, 2H), 3.52 (dd, J = 3.6, 10.9 Hz, 2H), 4.92 (d, J = 2.18 Hz, 1H), 5.22 (d, J =
.0 Hz, 1H), 6.45 (d, J = 8.0 Hz, 1H), 6.92 (dd, J = 2.1, 8.0 Hz, 1H), 7.22-7.30 (m, 3H),
+
.40 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 1H); MS (ESI) m/z 386 ([M+H]) . Anal.
Calcd. for C21
H24BrNO: C, 65.29; H, 6.26; Br, 20.68; N, 3.63; O, 4.14. Found: C, 65.26;
H, 6.26; N, 3.61.
9

o
-1
Trans isomer: Mp 94-95 C; Rf (20% EtOAc/n-hexane) 0.45.; IR (KBr) (νmax, cm ):
1
3
1
1
368 (N-H), 2936, 2860, 1493, 1067, 818; H NMR (300 MHz, CDCl
3
), : 1.94 (s, 3H),
.23 (s, 3H), 1.39-1.54 (m, 2H), 2.02-2.13 (m, 1H), 2.72-2.82 (m, 1H), 3.62 (dt, J = 2.1,
1.65 Hz, 2H), 4.04 (dd, J = 2.1, 11.6 Hz, 2H), 4.30 (d, J = 2.1 Hz, 1H), 4.60 (d, J = 10.9
Hz, 1H), 6.45 (d, J = 8.0 Hz, 1H), 6.95 (dd, J = 2.1, 8.0 Hz, 1H), 7.01-7.02 (d, J = 2.18,
+
2
H), 7.28 (d, J = 8.01 Hz, 2H), 7.48 (d, J = 8.7 Hz, 1H); MS (ESI) m/z 386 ([M+H]) .
Anal. Calcd. for C21
H24BrNO: C, 65.29; H, 6.26; Br, 20.68; N, 3.63; O, 4.14. Found: C,
6
5.28; H, 6.27; N, 3.65.
9
-Fluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (4 & 5l): Cis
o
1
isomer : Mp 158-159 C; Rf (20% EtOAc/n-hexane) 0.5.; H NMR (300 MHz, CDCl
3
), :
1
.37-1.55 (m, 4H), 2.14 (m, 1H), 3.42 (dt, J = 3.02, 11.3Hz, 1H), 3.60 (dd, J = 3.02, 11.3
Hz, 1H), 3.70 (br s, 1H,), 4.63 (d, J = 3.0 Hz, 1H), 5.23 (d, J = 6.0 Hz 1H), 6.45-6.49 (d,
J = 4.5 Hz, 1H), 6.78 (dt, J = 3.0, 8.3 Hz, 1H), 7.08-7.12 (dd, J = 3.0, 8.3 Hz, 1H), 7.24-
+
7
6
.39 (m, 5H); MS (ESI) m/z 284 ([M+H]) . Anal. Calcd. for C18
H18FNO: C, 76.30; H,
.40; F, 6.71; N, 4.94; O, 5.65. Found: C, 76.29; H, 6.40; N, 4.91.
o
1
Trans isomer : Mp 82-84 C; Rf (20% EtOAc/n-hexane) 0.48.; H NMR (300 MHz,
CDCl ), : 1.31-1.50 (m, 2H), 1.57-1.68 (m, 1H), 1.75-1.87 (m, 1H); 2.07 (m, 1H), 3.71
dt, J = 2.2, 11.3 Hz, 1H), 3.91 (br s, 1H), 4.08 (dd, J = 3.7, 10.5 Hz, 1H), 4.31 (d, J = 2.2
3
(
Hz, 1H), 4.64 (d, J =10.5 Hz, 1H), 6.39-6.44 (2d, J = 4.5 Hz, 1H), 6.81(dt, J = 3.0, 8.3
Hz, 1H), 6.88-6.92 (dd, J = 3.0, 9.0 Hz, 1H), 7.24-7.39 (m, 5H); MS (ESI) m/z 284
1
0

+
(
[M+H]) . Anal. Calcd. for C18
H18FNO: C, 76.30; H, 6.40; F, 6.71; N, 4.94; O, 5.65.
Found: C, 76.29; H, 6.41; N, 4.95.
2
-Fluoro-6-(4-fluoro-phenyl)-5,6a,7,8,9,10a-hexahydro-6H-phenanthridin-10-one (4
o
1
&
5n): Cis isomer : Mp 118-120 C; Rf (20% EtOAc/n-hexane) 0.5.; H NMR (300 MHz,
), : 1.56-1.94 (m, 3H), 2.26-2.36 (m, 2H), 2.58-2.74 (m, 2H), 4.36-4.40 (m, 1H),
.64 (d, J = 3.1 Hz, 1H), 6.40-6.46 (m, 2H), 6.72-6.81 (t, J = 7 .8 Hz, 1H), 7.32-7.34 (m,
CDCl
3
4
4
1
+
H); MS (ESI) m/z 314 ([M+H]) . Anal. Calcd. for C19
H
17
F
2
NO: C, 72.83; H, 5.47; F,
2.13; N, 4.47; O, 5.11. Found: C, 72.80; H, 5.46; N, 4.45.
o
1
Trans isomer : Mp 114-115 C; Rf (20% EtOAc/n-hexane) 0.45.; H NMR (300 MHz,
CDCl
3
), : 1.68-1.79 (m, 2H); 1.99-2.30 (m, 2H), 2.38-2.45 (m, 2H), 2.69-2.77 (m, 2H),
4
1
7
.36-4.42 (m, 1H), 4.54 (d, J = 2.0 Hz, 1H), 6.50-6.55 (m, 2H), 6.79-6.81 (t, J = 8.3 Hz,
+
H), 7.21-7.32 (m, 4H); MS (ESI) m/z 314 ([M+H]) . Anal. Calcd. for C19
H
17
2
F NO: C,
2.83; H, 5.47; F, 12.13; N, 4.47; O, 5.11. Found: C, 72.85; H, 5.47; N, 4.45.
1
2-(2-Chloro-phenyl)-2,3,4a,11,12,12a-hexahydro-1H-4-oxa-11-aza-chrysene (Table
o
1
2
, entry r): Cis isomer : m.p. 152-154 C; Rf (20% EtOAc/n-hexane) 0.5.; H NMR (300
), : 1.21-1.59 (m, 3H), 2.48 (m, 1H), 3.29-3.36 (m, 1H), 3.52-3.61 (m, 1H),
.29-4.30 (m, 1H), 5.18 (d, J = 2.6 Hz, 1H), 5.45 (d, J = 6.4, Hz 1H), 7.17-7.35 (m, 2H),
MHz, CDCl
3
4
7
.37-7.45 (m, 5H), 7.48-7.54 (m, 2H), 7.93 (d, J = 2.07 Hz, 1H); MS (ESI) m/z 350
+
(
[M+H]) . Anal. Calcd. for C22
H20ClNO: C, 75.53; H, 5.76; Cl, 10.13; N, 4.00; O, 4.57.
Found: C, 75.53; H, 5.74; N, 4.01.
1
1

1
Trans isomer : Thick syrup; Rf (20% EtOAc/n-hexane) 0.48.; H NMR (300 MHz,
CDCl ), : 1.20-1.65 (m, 3H), 2.29 (m, 1H), 3.36-3.55 (m, 1H), 3.63-3.64 (m, 1H), 4.19-
.60 (m, 1H), 4.61 (d, J = 3.6 Hz, 1H), 5.31 (d, J = 10.9 Hz, 1H), 6.67-7.46 (m, 6H),
3
4
7
+
.62-7.78 (m, 4H); MS(ESI) m/z 350 ([M+H]) . Anal. Calcd. for C22H20ClNO: C, 75.53;
H, 5.76; Cl, 10.13; N, 4.00; O, 4.57. Found: C, 75.55; H, 5.75; N, 4.04.
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
ACKNOWLEDGMENTS
The author’s gratefully acknowledge Director CSIR-IICT, Hyd. and Head, Organic and
Biomolecular Chemistry Division, CSIR-IICT for their constant encouragement and
support.
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4

Figure 1.
1
5

Scheme 1.
1
6

Scheme 2.
1
7

Scheme 3.
1
8