Friedel-Crafts Chemistry. Part 43. A Convergent Construction of Some New Bridged Aza-Bicyclic Analogues of Azocine, Azonine, and Azecine via Friedel-Crafts Ring Closures

Article abstract of DOI:10.1071/CH14284

Our present study provides an expedient general approach for the synthesis of some novel bridged dibenzo-azocinone, -azoninone, -azecinone, -azocine, -azonine, and -azecine derivatives via Friedel-Crafts intramolecular ring-closure reactions. The methodol

Full text of DOI:10.1071/CH14284

CSIRO PUBLISHING
Aust. J. Chem. 2015, 68, 404–415
Full Paper
http://dx.doi.org/10.1071/CH14284
Friedel–Crafts Chemistry. Part 43. A Convergent
Construction of Some New Bridged Aza-Bicyclic
Analogues of Azocine, Azonine, and Azecine
via Friedel–Crafts Ring Closures
A B
,
A
Hassan A. K. Abd El-Aal,
Ali A. Khalaf,
A
and Ahmed M. A. El-Khawaga
A
Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt.
Corresponding author: Email: hassankotb33@yahoo.com
B
Our present study provides an expedient general approach for the synthesis of some novel bridged dibenzo-azocinone,
-azoninone, -azecinone, -azocine, -azonine, and -azecine derivatives via Friedel–Crafts intramolecular ring-closure
reactions. The methodology is realized by a four-step protocol involving first preparation of 7-methyl-3,3-diphenylindoline
through the reduction of 7-methyl-3,3-diphenylindolin-2-one followed by N-alkylations with different haloesters (a-, b- or
g-). The resulting indoline ester derivatives were allowed to react both by addition of Grignard reagents to afford alcohols
and by hydrolysis to afford acids. Particular attention has been given to the novel structures especially in regard to the
promising pharmaceutical and therapeutic values associated with their skeletons.
Manuscript received: 6 May 2014.
Manuscript accepted: 28 May 2014.
Published online: 1 September 2014.
Introduction
N
Medium-sized nitrogen heterocycles (particularly benzfused
azepines, azocines, azonines, and azecines)[1] are key structural
moieties found in a large number of biologically active phar-
maceuticals[2] and natural products[3] (alkaloids) (Fig. 1).
Moreover, they have been used as building blocks for the syn-
thesis of some organic semiconductors,[4] dyes,[5] and poly-
mers.[6] More interestingly, studies have shown that these
compounds when properly functionalized may exhibit diverse
medical functions in various biologically active molecules pos-
sessing antidepressant, anticancer, analgesic, antihypertensive,
antiviral, anti-epileptic, antiseizure, anticonvulsant, anti-
inflammatory, antimicrobial, antimalarial, antioxidant, anthel-
mintic, and antitumour activities.[7]
N
NH
Azonine
NH
Azepine
Azocine
Azecine
N
N
MeO
MeO
N
N
H
H
H
NMe
H
COOMe
Apparicine
Buflavine
Vincadine
MeO
MeO
CH3
N
NMe
N
H
MeO
OMe
Protostephanine
Dopamine receptor antagonists (LE300)
The wide pharmacological potentials of these bioactive
moieties have attracted many organic and medicinal chemists
to develop efficient routes for their synthesis.[8] However, the
unfavourable enthalpy and entropy factors, as well as the
transannular interactions expected in such molecules hindered
the adaptation of traditional methods of ring formation.[9]
Accordingly, multistep strategies that primarily require appro-
priate design of starting substrates and a succession of reaction
steps have mostly been adopted to access such medium-sized
bridged azacarbocycles.[10] The methods developed made use
of known reactions, such as: ring-closing metathesis,[11]
Diels–Alder reaction,[12] Cope rearrangement,[13] transition
metal-catalyzed cycloaddition,[14] sigmatropic cyclization,[15]
radical-mediated ring expansion and fragmentation,[16] domino
reactions,[17] intramolecular photocycloaddition,[18] Fischer
carbene complexes (FCCs),[19] and intramolecular Schmidt
Fig. 1. Pharmaceuticals containing 5H-Dibenz[b,f]azocine, azonine, and
azecine templates.
reaction of azidoalkyl ketones.[20] In spite of this, the synthesis
of azonine and azecine azacyclic derivatives remains relatively
undeveloped except for a few cases such as in the synthesis of
dopamine receptor antagonists and in natural isolated alkaloids
such as erythrina, cephalotaxus, laurifonine, and vincristine.[21]
Likewise, the reported numbers of synthetic approaches to the
carbopolycyclic azocine scaffold and its benzo- and dibenzo-
derivatives are also limited. Some of the important applied
strategies are presented in the following. Gil and coworkers[22]
reported a facile synthesis of 1,2,7,8-tetrahydroazocine deriva-
tives by [2þ2] cycloaddition reactions[23] between enamines and
Journal compilation Ó CSIRO 2015
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Bridged Azatetracyclic Azocines, Azonines, and Azecines
405
R
O
O
R
R
R
N
N
S
N
S
a: R ϭ H
b: R ϭ Me
X
a: X ϭ S
b: X ϭ CHϭCH
O
O
2,3:6,7-Dibenzobicyclo[3.2.2]
nona-2,6-diene
Pyrrolothienothiazocines
Benzodiazocines
R
O
O
O
O
R3
N
N
N
N
R
R
S
X
S
S
S
Y
R
Z
X
O
O
O
R1 R2
Y
a: R ϭ H; X ϭ S; Y ϭ Z ϭ H
a: R ϭ R1 ϭ R2 ϭ R3 ϭ H
b: R ϭ NO2; R1 ϭ R2 ϭ O; R3 ϭ H
c: R ϭ H; R1 ϭ R2 ϭ O; R3 ϭ Me
a: X ϭ S; Y ϭ CH
b: X ϭ CH; Y ϭ S
a: R
ϭ H; b: R ϭ Br; c: R ϭ OMe
b: R ϭ H; X ϭ Y ϭ CH; Z ϭ H
c: R ϭ H; X ϭ CCl; Y ϭ S; Z ϭ CH
d: R ϭ Me; X ϭ S; Y ϭ Z ϭ CH
Tetracyclic thiazocines
Fig. 2. Fused heteropolycycles synthesized by Friedel–Crafts cyclialkylations.
ethyl propiolate followed by electrocyclic ring-opening to give
the azocine systems. Monro et al.[24] (1963) described an
interesting one-step regioselective synthesis of tetrahydro-5H-
dibenz[b, f ]azocin-11-one derivatives via Beckmann rearrange-
ment of dibenzosuberone oximes. Later (1998–2006), an
identical methodology was employed to generate 2-arylated-1-
benzazocines,[25] dibenzazocine,[26] and apogalanthamine analo-
gues[27] having a tetrahydrodibenz[c,e]azocine moeity. In 2004,
Raw and Taylor[28] described an interesting reaction between
enamines with 1,2,4-triazines to produce functionalized 4,5-
dihydroazocines. In an alternative strategy, Cho et al.[29] (2010)
reported that treatment of cyclic ketoximes fused to aromatic
rings with di-isobutylaluminium hydride (DIBALH) resulted in a
reductive ring-expansion reaction, leading to a variety of five- to
eight-membered bicyclic heterocycles. Further, Polonka-Ba´lint
and coworkers[30] (2008) employed the tert-amino effect to
produce fused azocines. The synthesis was achieved in three
steps utilizing the Suzuki reaction, the Knoevenagel condensa-
tion, and thermal isomerization to fused azocines. In 2010, a
simple protocol for the synthesis of various dibenzazocines via
the intramolecular Heck reaction as a key step was developed by
Majumdar and coworkers.[31a] Later,[31b] they extended their
strategy to accomplish the synthesis of pyrimidine-fused azocine
derivatives from substituted allylamines. Another widely used
methodology that has been successfully applied by several
authors in the synthesis of azocines is the ring-closing metathesis
(RCM)[32] of dienes, enynes, and amides using Schrock’s,
Grubbs’, and alkylidene catalysts in the key steps.
small enthalpic cost and large entropic cost in the transition
state but little to no entropic cost in the product cycle. Moreover,
elimination of transannular interactions in the synthesis of
medium-sized rings comes at the cost of minimized Baeyer
and Pitzer strains. These interactions could be diminished by
applying harsher conditions (longer reaction time or higher
temperature with more catalyst).[39]
It appears obvious from the foregoing introduction that the
syntheses of benzfused azepines, azocines, azonines, and
azecines are relatively limited and building them is not simple.
That implies that this subject is still a matter of continuing
challenge. That inspired us to start a systematic study based on
our long experience in Friedel–Crafts reactions to develop ring-
closure strategies for the construction of bridged and non-
bridged medium-sized heteropolycycles. In our previous
work,[40–43] we introduced novel methods for the construction
of nine substituted 10,11-dihydro-5H-dibenz[b,f]azepines
(iminodibenzyls), 5,6,11,12-tetrahydro-5H-dibenz[b,f]azocines,
5,6-dihydro-11H-benzo[f]pyrido[2,3-b]azepines, and 5,6,11,12-
tetrahydro-6H-benzo[g]pyrido[2,3-c]azocines via Friedel–Crafts
ring closures of nitrogen-containing alcohols and carboxylic
acids.
In this paper, we present our endeavours in the development
of cyclialkylation[43] approaches to yield facile access to several
new dibenzo-azepine, -azocine, -azonine, and -azecine skele-
tons of promising pharmacological activities.
Results and Discussion
Finally, it is worthy of note that scattered instances of the use
of Friedel–Crafts ring-closure reactions in the synthesis of
medium-sized azacarbocycles can also be found in the chemical
literature.[33] Examples of these reactions can notably be seen in
the synthesis of dibenzobicyclo[3.2.2]nona-2,6-diene deriva-
tives.[34] Moreover, the latter feature strongly in the synthesis
of tetracyclic thiazocines,[35] pyrrolothienothiazocines,[36] and
benzodiazocines[37] (Fig. 2).
The reaction was considered as one of the macrocyclization
strategies (including carbocyclizations, macrolactonizations,
and macrolactamizations) for the synthesis of medium-sized
rings.[38] These constructive reactions are characterized by
Synthesis of Starting Ring-Closure Substrates
7a–c and 8a–f
Scheme 1 outlines the synthesis of key intermediate 5 and of
heterocyclic ring-closure precursors acids 7a–c and alcohols
8a–f. As shown in scheme 1, reaction[44] of 2-chloro-2,2-
diphenylacetyl chloride (2)[45] with o-toluidine (1) in ether
afforded 2-chloro-2,2-diphenyl-N-o-tolylacetamide (3). The lat-
ter chloranilide was converted to 7-methyl-3,3-diphenylindolin-
2-one (4) by heating with AlCl3 in chlorobenzene with stirring in
an oil bath at 150–608C for 3 h. Reduction of diphenyloxindole 4
with LiAlH4 in THF[46] gave 7-methyl-3,3-diphenylindoline (5).

406
H. A. K. Abd El-Aal, A. A. Khalaf, and A. M. A. El-Khawaga
Ph
Ph
Ph
Ph
Ph
Ph
Cl
ii
iii
O
O
N
H
N
N
H
H
3
4
5
Br
COOEt
iv
Ph
Ph
Cl
n
C
i
4a–c
COCl
Ph
Ph
OH
Ph
Ph
Ph
2
Ph
vi
v
N
N
N
NH2
R
COOH
n
COOEt
n
R
n
1
7a–c
6a–c
8a–f
d: n ϭ 1, R ϭ Ph
e: n ϭ 2, R ϭ Me
f: n ϭ 2, R ϭ Ph
n ϭ 0 or 1 or 2
a: n ϭ 0, R ϭ Me
b: n ϭ 0, R ϭ Ph
c: n ϭ 1, R ϭ Me
Scheme 1. Reagents and conditions: (i) Et2O, 3h, 08C; (ii) AlCl3/PhCl, 3h, 1558C; (iii) LiAlH4/THF, 2 h, 08C;
(iv) haloester, K2CO3/DMF, 1008C; (v) NaOH, 2–3 h, reflux, HCl; (vi) MeMgX, THF/Et2O, room temperature (rt), 6 h,
NH4Cl solution.
Table 1. Conditions and results for the synthesis of alcohols 8a–f
rt, room temperature
Entry
Starting material
Product
ConditionsA
Mp [8C] (n2D5
)
Product [%]B
n
R
1
2
3
4
5
6
6a
6a
6b
6b
6c
6c
0
0
1
1
2
2
Me
Ph
MeMgI, Et2O, rt, 4 h
162
(1.564)
138
8a (88)
8b (84)
8c (89)
8d (90)
8e (92)
8f (90)
PhMgBr, Et2O, rt, 12 h
MeMgI, Et2O, rt, 8 h
Me
Ph
PhMgBr, THF/Et2O, rt, 10 h
MeMgI, Et2O, rt, 6 h
94
Me
Ph
(1.544)
105
PhMgBr, THF/Et2O, rt, 11 h
AAll reactions were performed using 0.4 equiv. excess of RMgX.
BIsolated yield with reference to substrate.
Ph
Ph
Ph
Base-catalyzed N-alkylation of
5 with a-, b-, and
g-haloesters 4a–c gave esters 6a–c. The resulting N-esters were
further reacted in two different ways: hydrolyzed with KOH in
methanol to furnish acids 10a–d, and treated with a little more
than two equivalents of Grignard reagents[47] to afford the
corresponding tertiary alcohols 8a–f (R ¼ Me or Ph). The
conditions used and results of the production of alcohols 8a–f
are given in Table 1. The structures of all new alcohols were
appropriately established by both elemental and spectral
analyses.
Catalyst
Hϩ, ϪH2O
N
O
N
COOH
n
n
7a–c
9a: n ϭ 1; 10a: n ϭ 2; 11a: n ϭ 3
a: n ϭ 0; b: n ϭ 1; n ϭ 2
Scheme 2. Cycliacylations of acids 7a–c by AlCl3/CH3NO2, P2O5 or PPA
catalysts (see Table 2).
The 1H NMR data allowed an unambiguous confirmation of
the formation of the heterocyclic alkanols. For example, the
1H NMR spectrum for alcohol 8a displays six signals in which
aromatic protons appear at d 6.55–7.50 ppm and gem-dimethyl
groups at C-1 and C-2 appear as one singlet at d 1.25 ppm. The
third broad singlet at d 2.10 ppm shown to be exchangeable on
shaking with D2O was assigned to the OH group, whereas the
fourth singlet at d 3.60 ppm displayed as upfield shielded
protons was assigned to the methylene group attached to nitro-
gen. However, cyclic indoline CH2 protons with low local
electron density due to a neighbouring electronegative hetero-
atom and dibenzylic carbon are deshielded protons and appear
as a singlet at d 4.25 ppm. Further, in all IR spectra, the
characteristic peaks of carbonyl groups were absent.
Ring Closures (Cycliacylations) of Indoline-N-Carboxylic
Acids 7a–c
Ring closures of carboxylic acids 7a–c were effected by heating
with AlCl3/CH3NO2, polyphosphoric acid (PPA)[43,48] or P2O5
catalysts under different reaction conditions to provide azate-
tracyclic ketones 9a, 10a, and 11a (Scheme 2 and Table 2). The
structures of 9a, 10a, and 11a were confirmed by both analytical
and spectral data.
Ring Closures (Cyclialkylations) of Indolinyl Alkanols 8a–f
The cyclialkylations of alkanols 8a–f were again induced in the
presence of AlCl3/CH3NO2, PPA or P2O5 catalysts under

Bridged Azatetracyclic Azocines, Azonines, and Azecines
407
Table 2. Friedel–Crafts cycliacylations of indoline-N-carboxylic acids 7a–c
DCM, dichloromethane; PPA, polyphosphoric acid
Entry
1
Substrate
Ph
Product
Conditions
Product [%]A
AlCl3/CH3NO2,B DCM, 15 h, reflux
P2O5,C toluene, 18 h, reflux
PPA,D 10 h, 190–2008C
9a (84)
9a (91)
9a (75)
Ph
Ph
N
O
7a
N
COOH
9a
2
3
Ph
Ph
AlCl3/CH3NO2, DCM, 8 h, reflux
P2O5, toluene, 10 h, reflux
PPA, 5 h, 190–2008C
10a (90)
10a (88)
10a (80)
Ph
N
O
7b
7c
COOH
N
10a
11a
Ph
Ph
AlCl3/CH3NO2, DCM, 4 h, reflux
P2O5, toluene, 5 h, reflux
PPA, 2 h, 190–2008C
11a (83)
11a (93)
11a (85)
Ph
N
COOH
O
N
AIsolated yield with reference to substrate.
BWith AlCl3/CH3NO2 catalyst, reactant proportions were: carbinol, 0.002 mol; AlCl3, 0.0024 mol; CH3NO2, 0.024 mol; solvent, 10 mL.
CWith P2O5 catalyst, reactant proportions were: carbinol or acid, 0.4 g; and P2O5, 4 g in anhydrous toluene, 15 mL.
DWith PPA catalyst, reactant proportions were: carbinol or acid, 0.5 g; and PPA, 5 g.
Ph
Ph
Ph
Ph
Ph
ϩ
Cat.
ϪH
R
R
N
OH
N
ϩ
R
ϩ
H , ϪH2O
R
R
N
n
R
n
n
9b: n ϭ 1, R ϭ Me
9c: n ϭ 1, R ϭ Ph
10b: n ϭ 2, R ϭ Me
10c: n ϭ 2, R ϭ Ph
11b: n ϭ 3, R ϭ Me
11c: n ϭ 3, R ϭ Ph
8a–f
a: n ϭ 0, R ϭ Me d: n ϭ 1, R ϭ Ph
b: n ϭ 0, R ϭ Ph e: n ϭ 2, R ϭ Me
c: n ϭ 1, R ϭ Me
f: n ϭ 2, R ϭ Ph
Scheme 3. Cyclialkylations of alkanols 8a–f under Friedel–Crafts conditions (see Table 3).
varying conditions (Scheme 3 and Table 3). On one hand and as
evident from Table 2, the closure of carbinols 8a, c, e (R ¼ Me)
proceeded smoothly by treatment with AlCl3/CH3NO2, P2O5 or
PPA catalyst under varying reaction conditions in only 2–5 h.
The corresponding bridged dibenzobicyclic diazepine, azocine,
and azonine (9b, 10b, and 11b respectively) were all obtained in
good yields.
On the other hand, the ring closures of alcohols 8b, d, f where
R ¼ Ph required more strenuous reaction conditions compared
with their methyl counterparts 8a, c, e (Table 3). For example,
the best results for alcohol 8d were obtained by treatment with
AlCl3/CH3NO2 in DCM for 44 h at room temperature, with P2O5
in toluene under reflux for 20 h or with PPA for 12 h at 210–
2208C to yield 4-methyl-7,7,12-triphenyl-6,7,12-trihydro-5H-
5,12-methano-dibenzo[b,e]azocine (10c) as the sole product.
These results can be attributed to two factors: (i) the steric
hindrance exerted by the two phenyl groups on the ring-closure
step of the tertiary diphenylated carbocation,[49] and (ii) the
lower electrophilic reactivity of this carbocation as a result of
the delocalization of charge over the two phenyl groups. The
structures of all new heteropolycycles were appropriately estab-
lished by both elemental and spectral analyses.
A plausible carbocation mechanism to account for the above
results is realized on the generation of tertiary carbocations by
loss of water upon treatment of the alcohols with acidic catalysts
(Scheme 3). The resulting carbocations undergo ring closures to
the correspondingly substituted dibenzo-azepines, -azocines,
and -azonines of Table 3.
The assignment of the diastereotopic protons of cyclic
methylene hydrogens was based on the environmental electron-
ic effects exerted by both the heteroatom and the neighbouring
functional groups[50] on the J values obtained by direct inspec-
tion of the 1H NMR spectrum. A closer look at the cyclic
structures (9a–c, 10a–c, and 11a–c) confirmed that such
molecules comprise cyclic diastereotopic methylene protons
(Fig. 3).
1
Thus, the H NMR for product 9a is characterized by the
presence of five signals in which aromatic protons appear at
d 6.55–7.45 ppm, the methyl group appears as a singlet near
d 2.35 ppm, and cyclic CH2 as a characteristic singlet at d
6
4.74 ppm. As expected, the remaining two signals characteristic
of bridged methylene hydrogens (Ha and Hb) appear as diaster-
eotopic CH2 protons exhibiting a complex set of overlapped
signals that are shielded and displayed a set of signals with

408
H. A. K. Abd El-Aal, A. A. Khalaf, and A. M. A. El-Khawaga
Table 3. Friedel–Crafts ring closures alkanols 8a–f
DCM, dichloromethane; PPA, polyphosphoric acid; rt, room temperature
Entry
1
Substrate
Ph
Product
Ph
Conditions
Product [%]
AlCl3/CH3NO2, DCM, 2 h, rt
P2O5, toluene, 5 h, reflux
PPA, 2 h, 210–2208C
9b (88)
9b (91)
9b (83)
Ph
N
OH
N
8a
8b
9b
9c
2
Ph
Ph
Ph
AlCl3/CH3NO2, DCM, 40 h, rt
P2O5, toluene, 24 h, reflux
PPA, 10 h, 210–2208C
9c (89)
9c (85)
9c (82)
N
Ph
Ph
OH
Ph
N
Ph
3
4
Ph
Ph
OH
AlCl3/CH3NO2, DCM, 2 h, rt
P2O5, toluene, 3 h, reflux
PPA, 1 h, 210–2208C
10b (93)
10b (91)
10b (80)
Ph
N
N
10b
8c
8d
8e
Ph
Ph
OH
Ph
Ph
AlCl3/CH3NO2, DCM, 44 h, rt
P2O5, toluene, 20 h, reflux
PPA, 12 h, 210–2208C
10c (86)
10c (87)
10c (85)
Ph
Ph
Ph
N
N
10c
11b
5
6
Ph
Ph
AlCl3/CH3NO2, DCM, 4 h, rt
P2O5, toluene, 4 h, reflux
PPA, 2h, 210–2208C
11b (90)
11b (89)
11b (86)
Ph
N
OH
N
Ph
Ph
AlCl3/CH3NO2, DCM, 8 h, rt
P2O5, toluene, 24 h, reflux
PPA, 14 h, 210–2208C
11c (90)
11c (89)
11c (86)
Ph
N
Ph
Ph
OH
Ph
Ph
11c
N
8f
4Ј
5Ј
3Ј
6Ј
10
10
11
10
11
11
Ph
12
2'
Ph
12
1Ј
9
9
11a
9
11a
11a
1
1
1
12
8
8
8
2
2
3
2
3
7a
7a
7a
2ٞ
3ٞ
7
7
7
1ٞ
3
6
O
4a
4a
4a
4ٞ
4
N
5
4
N
5
4
N
5
6Љ
6
1Љ
6
6ٞ
5Љ
4Љ
5ٞ
2Љ
9a
9b
9c
3Љ
Fig. 3. Diastereotopic protons embraced in dibenzfused azocines heteropolycycles.
different values of coupling constants. The bridged cyclic CH2
protons (Ha and Hb) of the skeleton of 9a revealed two sets of
somewhat separated signals as a doublet at d 4.23 and triplet near
d 4.41 ppm with a coupling constant of 9.3 Hz.
In comparison with the diastereotopic protons of the azoci-
none skeleton of 9a, dibenzo[b,e]azocine 9b showed 1H NMR
chemical shifts in CDCl3 for the diastereotopic bridged azocine
CH2 protons (Ha and Hb) as two resolved signals in the form of a
doublet of doublets near d 4.22 ppm and triplet near d 4.52 ppm
respectively.
Conclusions
In summary, we have developed a novel, facile, and catalytic
protocol for the synthesis of some new medium-sized dibenzo-
bridged azacarbocyclic azocines, azonines, and azecines uti-
lizing Friedel–Crafts ring closure of suitably synthesized
indoline-based acid and alcohol substrates. This attractive
method provides great potential to induce skeletal ring closures
of unique nitrogen skeletons in excellent yields and high
selectivities in short reaction times. The simplicity and wide

Bridged Azatetracyclic Azocines, Azonines, and Azecines
409
versatility of the applied method makes it a good alternative to
the lengthy multistep protocols usually employed.
(iii) A solution of amide 4 (2.5 g, 11.8 mmol) in anhydrous THF
(15 mL) was added over a period of 5 min to a cold (08C)
solution of lithium aluminum hydride, LiAlH4 (0.45 g,
11.8 mmol) in ether (15 mL). The reduction was complete
after stirring and refluxing for 2 h on a steam bath (TLC,
40 % ethyl acetate/hexanes). The reaction mixture was
then cooled to 08C and quenched by the sequential addition
of distilled water (0.5 mL), 20 % aqueous NaOH solution
(0.5 mL), and distilled water (1.3 mL); then it was allowed
to warm to room temperature. Suction filtration removed
the white precipitate of aluminium compounds, which
were thoroughly triturated with ethyl acetate and with
THF. The combined organic phases were evaporated under
vacuum to afford the crude base. Crystallization from
petroleum spirit (60–808C) gave 1.8 g (74.6 %) of pure
7-methyl-3,3-diphenylindoline (5) in the form of white
crystals; mp 152–1548C. nmax (KBr)/cmꢀ1 3410, 3045,
2975, 1600, 1585, 1480, 1445, 1375, 1245, 750. dH
(60 MHz, CDCl3) 2.3 (s, 3H, CH3), 3.8 (s, 2H, CH2), 4.1
(s, 1H, NH), 6.40–7.60 (m, 13H, Ar–H). Anal. calc. for
C21H19N (285): C 88.42, H 6.66, N 4.91. Found: C 88.58,
H 6.47, N 4.93 %.
Experimental
General
All reagents were purchased from Merck or Sigma–Aldrich and
were used without further purification. Melting points were
measured on a digital Gallenkamp capillary melting point
apparatus and are uncorrected. IR spectra were determined with
a Shimadzu 470 infrared spectrophotometer using KBr wafer
and thin-film techniques (n, cmꢀ1). The 1H NMR and 13C NMR
spectra were recorded on JEOL LA 400 MHz Fourier-transform
(FT)-NMR (400 MHz for 1H, 100 MHz for 13C) and on Varian
NMR (60 MHz) spectrometers using CDCl3 solvent with TMS
as internal standard. Chemical shifts (d) and J values are
reported in ppm and Hz respectively. Elemental analyses were
performed on a Perkin–Elmer 2400 Series II analyser. Mass
spectra were recorded with a JEOL JMS 600 spectrometer at an
ionizing potential of 70 eV (EI) electron impact ionization using
the direct inlet system. Refractive index was measured using an
Abbe refractometer at sodium D-line wavelength (589.3 nm) at
258C (n2D5). Reactions were monitored by thin-layer chromato-
graphy (TLC) using precoated silica plates visualized with UV
light. Flash column chromatography was performed on silica gel
and basic alumina.
General Procedure for N-Alkylation of 7-Methyl-3,3-
diphenylindoline
To a hot (1008C) stirred solution of diphenylindoline 5 (1 g,
5.1 mmol) in DMF (10 mL) was added K2CO3 (2.1 g,
15.3 mmol) and a solution of (a-, b- or g-) haloesters 4a, b or c
(0.73 mL, 7.6 mmol) in DMF (10 mL) over a period of 10 min.
The reaction mixture was further heated at 1008C for 6 h (TLC,
25 % ethyl acetate/hexanes). The reaction mixture was poured
into ice-cold water and extracted with ethyl acetate (2 ꢁ 25 mL).
The combined organic layers were washed with water and dried
over anhydrous Na2SO4. Evaporation of the solvent under
vacuum afforded the crude products. Purification of the crude
esters by flash column chromatography (basic alumina, EtOAc/
n-hexane, 1 : 1) gave pure esters 6a–c. The yields, and further
purification and spectral data are given in the following.
Synthesis of 7-Methyl-3,3-diphenylindoline (5)
This acid was obtained in a series of three consecutive steps
starting with commercially available o-toluidine. A summary of
the steps is given in the following.
(i) To an ice-cold stirred solution of o-toluidine 1 (8.1 g,
75.6 mmol) in dry ether (130 mL) was added a solution
of chlorodiphenylacetyl chloride 2 (10 g, 37.7 mmol) in
ether (100 mL) over a period of 5 min at 08C. The reaction
was allowed to stand for 3 h at room temperature and then
filtered. The precipitate was washed with ether
(3 ꢁ 30 mL) and the combined ether washings were
washed with water, dried over anhydrous Na2SO4, and
concentrated until a thick mass of crystals remained. The
solid was filtered and washed with petroleum spirit to give
3.4 g (88 %) of crude acid. Crystallization from ether/
n-hexane gave 3.1 g (80 %) of chloroanilide 3 as white
needles; mp 858C. nmax (KBr)/cmꢀ1 3370, 3105, 2950,
1680, 1600, 1570, 1485, 1440, 1340, 1170, 745, 716, 678.
dH (60 MHz, CDCl3) 2.2 (s, 3H, CH3), 6.5–7.7 (m, 14H,
Ar–H), 9.5 (s, 1H, NH). Anal. calc. for C21H18ClNO
(335.5): C 75.11, H 5.36, Cl 10.58, N 4.17. Found: C
75.31, H 5.14, Cl 10.40, N 4.25 %.
Ethyl 2-(7-methyl-3,3-diphenylindolin-1-yl)acetate (6a)
Pale yellow needles; 84 %; mp 75–768C (benzene). nmax
(film)/cmꢀ1 3030, 2965, 1725, 1600, 1590, 1460, 1445, 1335,
1275, 750. dH (60 MHz, CDCl3) 1.25 (t, 3H, J 7.5, CH3), 2.35 (s,
3H, CH3), 4.1 (t, 2H, J 7.5, CH2), 4.20 (s, 2H, CH2), 4.40 (s, 2H,
CH2), 6.50–7.80 (m, 13H, Ar–H). Anal. calc. for C25H25NO2
(371):C80.86, H6.73, N3.77. Found: C 80.62, H 6. 92, N 3.85 %.
Ethyl 3-(7-methyl-3,3-diphenylindolin-1-yl)
(ii) A mixture of chloroanilide 3 (1 g, 3 mmol) and AlCl3 (1 g,
7.8 mmol) in chlorobenzene (2.5 g) was heated with stir-
ring in an oil bath at 150–608C for 3 h. The resultant
mixture was cooled to 08C, then poured into ice-cold
HCl solution (50 mL, 10 %). Separation and purification
of the product following a similar literature procedure gave
3.9 g (89 %) of crude product. Crystallization from ethanol
gave 3.6 g (84 %) of pure 7-methyl-3,3-diphenylindolin-2-
one (4) as cream crystals; mp 277–2788C. nmax (KBr)/cmꢀ1
3370, 3065, 2965, 1673, 1610, 1590, 1490, 1455, 1360,
1105, 1027, 815, 716, 658. dH (60 MHz, CDCl3) 2.25 (s,
3H, CH3), 6.5–7.6 (m, 13H, Ar–H), 8.9 (s, 1H, NH). Anal.
calc. for C21H17NO (299): C 84.28, H 5.68, N 4.68. Found:
C 84.42, H 5.53, N 4.62 %.
propanoate (6b)
White plates; 89 %; mp 62–638C (petroleum spirit 60–808C).
nmax (film)/cmꢀ1 3055, 2985, 1745, 1600, 1585, 1490, 1440,
1320, 1185, 745. dH (60 MHz, CDCl3) 1.25 (t, 3H, J 7.5, CH3),
2.35 (s, 3H, CH3), 2.50 (t, 2H, J 6, CH2), 3.65 (t, 2H, J 6, CH2),
4.1 (t, 2H, J 7.5, CH2), 4.25 (s, 2H, CH2), 6.45–7.50 (13H, m,
Ar–H). Anal. calc. for C26H27NO2 (385): C 81.03, H 7.01,
N 3.63. Found: C 81.23, H 6.85, N 3.77 %.
Ethyl 4-(7-Methyl-3,3-diphenylindolin-1-yl)
butanoate (6c)
Reddish viscous oil; 92 %; n2D51.575. nmax (film)/cmꢀ1 3070,
2965, 1740, 1610, 1580, 1490, 1440, 1340, 1235, 1185, 745. dH

410
H. A. K. Abd El-Aal, A. A. Khalaf, and A. M. A. El-Khawaga
(60 MHz, CDCl3) 1.25 (t, 3H, J 7.5, CH3), 1.85 (m, 2H, CH2),
2.25 (t, 2H, J 6, CH2), 2.35 (s, 3H, CH3), 3.45 (t, 2H, J 6, CH2),
4.15 (t, 2H, J 7.5, CH2), 4.15 (2H, s, CH2), 6.50–7.70 (13H, m,
Ar–H). Anal. calc. for C27H29NO2 (399): C 81.20, H 7.26,
N 3.50. Found: C 81.41, H 7.09, N 3.82 %.
2-Methyl-1-(7-methyl-3,3-diphenylindolin-1-yl)
propan-2-ol (8a)
White needles; 83 %; mp 162–1648C (ethanol). nmax (film)/
cmꢀ1 3450, 3080, 2970, 1600, 1580, 1460, 1450, 1355, 1025,
745. dH (60 MHz, CDCl3) 1.25 (s, 6H, 2CH3), 2.10 (s, 1H, OH
exchangeable with D2O), 2.25 (s, 3H, CH3), 3.60 (s, 2H, CH2),
4.25 (s, 2H, CH2), 6.55–7.50 (m, 13H, Ar–H). m/z (EI, 70 eV)
357 (Mþ, 24 %), 356 (32), 339 (100), 324 (25), 309 (37), 297
(61), 280 (33), 190 (14), 185 (53), 176 (11), 168 (29), 91 (17), 90
(10), 77 (5). Anal. calc. for C25H27NO (357): C 84.03, H 7.56,
N 3.92. Found: C 84.27, H 7.44, N 4.16 %.
General Procedure for the Synthesis of Propanoic
Acids 7a–c
A mixture of ester 6a, b or c (5 mmol) and excess NaOH solution
(15 mL, 20 %) was stirred under reflux for 2–3 h. After cooling
to room temperature, the clear solution was diluted with water
(30 mL) and poured with occasionally stirring into an ice-cold
dilute HCl solution (20 mL, 15 %). After standing for 6–8 h in
the refrigerator, the crude acid was filtered off and dissolved
with slight warming in NaHCO3 solution (15 mL, 20 %), fil-
tered, and acidified with HCl solution (25 mL, 10 %). The
product was filtered, washed, and dried to afford crude acids 7a,
b or c. Purification, yields and spectral data are given in the
following.
2-(7-Methyl-3,3-diphenylindolin-1-yl)-1,1-
diphenylethanol (8b)
Yellow viscous oil; 78 %; n2D51.564. nmax (KBr)/cmꢀ1 3380,
3095, 2960, 2850, 1580, 1478, 1450, 1440, 1330, 750, 670. dH
(60 MHz, CDCl3) 2.35 (s, 3H, CH3), 3.75 (s, 1H, OH exchange-
able with D2O), 4.15 (s, 2H, CH2), 4.30 (s, 2H, CH2), 6.60–7.95
(m, 23H, Ar–H). m/z (EI, 70 eV) 482 (Mþ þ 1, 8 %), 481 (Mþ,
100), 463 (74), 448 (31), 404 (11), 371 (18), 309 (16), 294 (20),
217 (31), 191 (21), 183 (42), 175 (9), 167 (24), 91 (12), 90 (9), 77
(6). Anal. calc. for C35H31NO (481): C 87.31, H 6.44, N 2.91.
Found: C 87.22, H 6.53, N 3.21 %.
2-(7-Methyl-3,3-diphenylindolin-1-yl)acetic Acid (7a)
White needles; 94 %; mp 152–1548C (methanol). nmax (KBr)/
cmꢀ1 3320, 3085, 2950, 2620, 1715, 1585, 1460, 1435, 1325,
745. dH (60 MHz, CDCl3) 2.35 (s, 3H, CH3), 4.20 (s, 2H, CH2),
4.35 (s, 2H, CH2), 6.50–7.80 (13H, m, Ar–H), 10.5 (s, 1H,
COOH). Anal. calc. for C23H21NO2 (343): C 80.46, H 6.12, N
4.08. Found: C 80.48, H 6.22, N 3.94 %.
2-Methyl-4-(7-methyl-3,3-diphenylindolin-1-yl)
butan-2-ol (8c)
White crystals; 82 %; mp 138–1408C (benzene). nmax (KBr)/
cmꢀ1 3410, 3065, 2920, 1590, 1575, 1450, 1435, 1330, 745. dH
(60 MHz, CDCl3) 1.20 (s, 6H, 2CH3), 1.65 (t, 2H, J 6, CH2), 2.35
(s, 3H, CH3), 3.55 (s, 1H, OH exchangeable with D2O), 3.15 (t,
2H, J 6, CH2), 4.20 (s, 2H, CH2), 6.60–7.55 (m, 13H, Ar–H). m/z
(EI, 70 eV) 371 (Mþ, 14 %), 353 (100), 338 (72), 323 (23), 308
(11), 276 (30), 199 (24), 190 (11), 184 (29), 176 (8), 167 (21), 91
(9), 90 (7), 77 (6). Anal. calc. for C26H29NO (371): C 84.09,
H 7.81, N 3.77. Found: C 83.84, H 7.92, N 3.95 %.
3-(7-Methyl-3,3-diphenylindolin-1-yl)propanoic
Acid (7b)
White crystals; 90 %; mp 122–1248C (benzene). nmax (film)/
cmꢀ1 3410, 3055, 2995, 2520, 1718, 1600, 1585, 1473, 1445,
1363, 1140, 755. dH (60 MHz, CDCl3) 2.35 (s, 3H, CH3), 2.45 (t,
2H, J 6, CH2), 3.60 (t, 2H, J 6, CH2), 4.25 (s, 2H, CH2), 6.55–
7.65 (13H, m, Ar–H), 10.8 (s, 1H, COOH). Anal. calc. for
C24H23NO2 (357): C 80.67, H 6.44, N 3.92. Found: C 80.62,
H 6.74, N 3.85 %.
3-(7-Methyl-3,3-diphenylindolin-1-yl)-1,1-
diphenylpropan-1-ol (8d)
4-(7-Methyl-3,3-diphenylindolin-1-yl)butanoic
Acid (7c)
Pale-yellow plates; 82 %; mp 94–958C (benzene). nmax
(KBr)/cmꢀ1 3450, 3050, 2970, 1605, 1590, 1480, 1460, 1445,
1345, 1020, 740. dH (60 MHz, CDCl3) 2.20 (t, 2H, J 6, CH2),
2.35 (s, 3H, CH3), 2.60 (s, 1H, OH exchangeable with D2O),
3.35 (t, 2H, J 6, CH2), 4.25 (s, 2H, CH2), 6.55–7.75 (m, 23H, Ar–
H). m/z (EI, 70 eV) 496 (Mþ þ 1, 7 %), 495 (Mþ, 48), 477 (100),
400 (46), 385 (14), 308 (26), 246 (17), 231 (9), 191 (8), 183 (15),
175 (12), 166 (14), 91 (14), 90 (11), 77 (4). Anal. calc. for
C36H33NO (495): C 87.27, H 6.66, N 2.82. Found: C 87.45,
H 6.52, N 2.75 %.
Pale yellow needles; 117 %; mp 92–948C (ethanol). nmax
(film)/cmꢀ1 3370, 3085, 2950, 2540, 1720, 1610, 1580, 1465,
1440, 1335, 1184, 745. dH (60 MHz, CDCl3) 1.75 (m, 2H, CH2),
2.25 (t, 2H, J 6, CH2), 2.35 (s, 3H, CH3), 3.40 (t, 2H, J 6, CH2),
4.15 (s, 2H, CH2), 6.50–7.75 (13H, m, Ar–H) 11.2 (s, 1H,
COOH). Anal. calc. for C25H25NO2 (371): C 80.86, H 6.73,
N 3.77. Found: C 81.04, H 6.55, N 3.94 %.
General Procedure for the Synthesis of Alcohols 8a–f
To an ice-cold Grignard reagent solution obtained as usual[38,39]
from Mg turnings (0.2 g, 8 mmol) and alkyl or aryl halide
(8 mmol) in ether (25 mL) was added a solution of ester 6a, b or c
(1 g, 3.3 mmol) in ether or THF (20 mL). The reaction mixture
was stirred at the required temperature for the assigned time
(Table 1), followed by decomposition with sat. aq. NH4Cl soln.
The product was extracted with ether (3 ꢁ 30 mL) and the
combined organic phases were washed with water and dried
over anhydrous Na2SO4. The solvent was removed under vac-
uum and the residue was purified by flash column chromato-
graphy (basic alumina, EtOAc/n-hexane, 1 : 1) to give the pure
products 8a–f. The conditions and yields are shown in Table 1
and spectral data are given below.
2-Methyl-5-(7-methyl-3,3-diphenylindolin-1-yl)
pentan-2-ol (8e)
Yellow viscous oil; 87 %; n2D51.544. nmax (KBr)/cmꢀ1 3460,
3045, 2970, 1595, 1570, 1455, 1440, 1336, 1020, 745. dH
(60 MHz, CDCl3) 1.20 (s, 6H, 2CH3), 1.30 (t, 2H, J 6, CH2),
1.55 (m, 2H, CH2), 2.10 (s, 1H, OH exchangeable with D2O),
2.35 (s, 3H, CH3), 3.20 (t, 2H, J 6, CH2), 4.25 (s, 2H, CH2), 6.60–
7.70 (m, 13H, Ar–H). m/z (EI, 70 eV) 386 (Mþ þ 1, 7 %), 385
(Mþ, 40), 367 (100), 352 (79), 337 (52), 322 (17), 307 (24), 290
(33), 270 (44), 260 (12), 190 (10), 185 (31), 176 (14), 168 (25),
90 (12), 90 (13), 77 (9). Anal. calc. for C27H31NO (385):
C 84.15, H 8.05, N 3.63. Found: C 84.12, H 7.84, N 3.88 %.

Bridged Azatetracyclic Azocines, Azonines, and Azecines
411
4-(7-Methyl-3,3-diphenylindolin-1-yl)-1,1-
diphenylbutan-1-ol (8f)
1070, 745. dH (400 MHz, CDCl3) 1.65 (approx. quint., J 7.4,
7CH2), 2.35 (s, 3H, CH3), 2.52 (t, 2H, J 7.4, 8CH2), 3.52 (t, 2H,
6
J 7.4, CH2), 4.16 (d, 1Ha, J 9.3, bridged CH2), 4.42 (d, 1Hb,
White needles; 86 %; mp 105–1078C (ethanol). nmax (KBr)/
cmꢀ1 3385, 3070, 2930, 1595, 1480, 1460, 1435, 1345, 1280,
1020, 745. dH (60 MHz, CDCl3) 1.45 (t, 2H, J 6, CH2), 1.85 (m,
2H, CH2), 2.35 (s, 3H, CH3), 2.75 (s, 1H, OH exchangeable with
D2O), 3.25 (t, 2H, J 6, CH2), 4.25 (s, 2H, CH2), 6.65–7.85 (m,
23H, Ar–H). m/z (EI, 70 eV), 520 (Mþ þ 1, 13 %), 519 (Mþ, 58),
501 (100), 486 (33), 424 (62), 409 (17), 347 (24), 335 (15), 270
(12), 255 (27), 193 (41), 191 (42), 180 (24), 178 (10), 166 (15),
90 (13), 90 (10), 77 (4). Anal. calc. for C37H35NO (509): C
87.22, H 6.87, N 2.75. Found: C 87.28, H 6.94, N 2.65 %.
J 9.3, bridged CH2), 6.57–7.75 (m, 12H, Ar–H). dC (100 MHz,
CDCl3) 16.1 (1C, CH3), 23.7 (1C, –CH2–, C-7), 41.4 (1C, –
CH2–CO, C-9), 49.4 (1C, C-14), 56.5 (1C, N–CH2–, C-6), 63.7
(1C, –CH2–, bridged), 118.7 (1C, Ar, C-2), 126.2 (2C, Ar,
C-1, C-11), 126.3 (1C, Ar, C-40), 127.5 (3C, Ar, C-3, C-4, C-
14a), 128.2 (1C, Ar, C-13), 128.3 (2C, Ar, C-20, C-60), 129.3
(3C, Ar, C-30, C-50, C-10), 133.7 (1C, Ar, C-12), 134.1 (1C, Ar,
C-9a), 143.1 (1C, Ar, C-13a), 143.6 (1C, Ar, C-10), 150.6 (1C,
Ar, C-4a), 205.9 (1C, C¼O, C-9). Anal. calc. for C25H23NO
(353): C 84.98, H 6.51, N 3.96. Found: C 84.72, H 6.65,
N 4.04 %.
Cyclialkylation Procedures
The procedures described earlier for cyclialkylations of
carboxylic acids 7a–c and arylalkanols 8a–f with AlCl3/
CH3NO2,[43] P2O5, and PPA[48] were essentially followed. The
crude oily or solid products were purified by flash column
chromatography (basic alumina, EtOAc/n-hexane, 2 : 1) and by
crystallizationfromsuitablesolventsfor the solid productstogive
the pure product. The conditions and yields for products 9a–c,
10a–c, and 11a–c are shown in Tables 2 and 3 while the physical
constants and spectral data of the products are given in the
following.
4,7,7-Trimethyl-12-phenyl-6,7,12-trihydro-5H-5,12-
methano-dibenzo[b,e]azocine (9b)
Yellowish viscous oil; 92 %; n2D5 1.589. nmax (film)/cmꢀ1
3045, 2980, 1600, 1585, 1490, 1445, 1373, 1285, 1025, 746. dH
(400 MHz, CDCl3) 1.35 (s, 6H, 2CH3), 2.36 (s, 3H, CH3), 3.72
(s, 2H, 6CH2), 4.22 (dd, 1Ha, J 6.5, bridged CH2), 4.52 (t, 1Hb, J
6.5, bridged CH2), 6.35–7.45 (m, 12H, Ar–H). dC (100 MHz,
CDCl3) 16.1 (1C, CH3), 27.2 (2C, –C(CH3)2), 28.3 (1C, C-7),
49.9 (1C, C-12), 64.3 (1C, –CH2–, bridged), 71.5 (1C, N–CH2–,
C-6), 118.7 (1C, Ar, C-2), 125.6 (1C, Ar, C-8), 125.9 (1C, Ar, C-
9), 126.2 (2C, Ar, C-1, C-10), 126.3 (1C, Ar, C-40), 127.5 (3C,
Ar, C-3, C-4, C-12a), 127.9 (1C, Ar, C-11), 128.3 (2C, Ar, C-20,
C-60), 129.3 (2C, Ar, C-30, C-50), 142.4 (1C, Ar, C-11a), 143.6
(1C, Ar, C-10), 150.6 (1C, Ar, C-4a), 150.9 (1C, Ar, C-7a). Anal.
calc. for C25H25N (339): C 88.49, H 7.37, N 4.12. Found: C
88.64, H 7.29, N 4.06 %.
4-Methyl-12-phenyl-6,7,12-trihydro-5H-5,12-methano-
dibenzo[b,e]azocin-7-one (9a)
White needles; 84 %; mp 142–1448C (benzene). nmax (KBr)/
cmꢀ1 3035, 2980, 1745, 1585, 1463, 1450, 1374, 1265, 1135,
1070, 745. dH (400 MHz, CDCl3) 2.35 (s, 3H, CH3), 4.23
(d, 1Ha, J 9.3, bridged CH2), 4.41 (app. t, 1Hb, J 9.3, bridged
CH2), 4.74 (s, 2H, 6CH2), 6.55–7.45 (m, 12 H, Ar–H).
dC (100 MHz, CDCl3) 16.1 (1C, CH3), 51.6 (1C, C-12), 63.5
(1C, –CH2–, bridged), 65.4 (1C, N–CH2–, C-6), 118.7 (1C, Ar,
C-2), 126.2 (2C, Ar, C-1, C-9), 126.3 (1C, Ar, C-40), 127.5 (3C,
Ar, C-3, C-4, C-12a), 128.2 (1C, Ar, C-11), 128.3 (2C, Ar, C-20,
C-60), 129.3 (3C, Ar, C-30, C-50, C-8), 133.7 (1C, Ar, C-10),
134.1 (1C, Ar, C-7a), 143.1 (1C, Ar, C-11a), 143.6 (1C, Ar,
C-10), 150.6 (1C, Ar, C-4a), 196.5 (1C, C¼O, C-7). Anal. calc.
for C23H19NO (325): C 84.92, H 5.84, N 4.30. Found: C 84.87,
H 5.93, N 4.40 %.
4-Methyl-7,7,12-triphenyl-6,7,12-trihydro-5H-5,12-
methano-dibenzo[b,e]azocine (9c)
White solid; 86 %; mp 138–1408C (petroleum spirit 60–
808C/benzene). nmax (KBr)/cmꢀ1 3065, 2930, 1595, 1568,
1475, 1440, 1375, 1285, 746. dH (400 MHz, CDCl3) 2.36
(s, 3H, CH3), 4.05 (d, Ha, J 9.3, bridged CH2), 4.22 (s, 2H,
6CH2), 4.45 (d, Hb, J 9.3, bridged CH2), 6.58–7.95 (m, 22H,
Ar–H). dC (100 MHz, CDCl3) 16.1 (1C, –CH3), 41.7 (1C, –C
(Ph)2, C-7), 49.9 (1C, C-12), 64.3 (1C, –CH2–, bridged), 71.3
(1C, N–CH2–, C-6), 118.7 (1C, Ar, C-2), 126.2 (1C, Ar, C-1),
126.3 (3C, Ar, C-40, 400, 4000), 126.8 (2C, Ar, C-9, C-10),010 27.5
(3C, Ar, C-3, C-4, C-12a), 128.3 (6C, Ar, C-20, 60, 200, 6 , 2000,
6000), 128.8 (2C, Ar, C-8, C-11), 129.3 (6C, Ar, C-30, 50, 300, 500,
3000, 5000), 143.6 (3C, Ar, C-10, 100, 1000), 145.6 (2C, Ar, C-7a,
C-11a), 150.6 (1C, Ar, C-4a). Anal. calc. for C35H29N (463):
C 90.71, H 6.26, N 3.02. Found: C 90.57, H 6.17, N 3.25 %.
4-Methyl-13-phenyl-6,7,8,13-tetrahydro-5H-5,13-
methano-dibenzo[b,e]azonin-8-one (10a)
Pale-yellow solid; 82 %; mp 134–1358C (ethanol). nmax
(KBr)/cmꢀ1 3065, 2940, 1740, 1605, 1590, 1475, 1440, 1383,
1270, 1135, 750. dH (400 MHz, CDCl3) 2.35 (s, 3H, CH3), 2.74
(t, 2H, J 7.4, 7CH2), 3.58 (t, 2H, J 7.4, 6CH2), 4.17 (d, 1Ha, J 9.3,
bridged CH2), 4.37 (approx. t, 1Hb, J 9.3, bridged CH2), 6.45–
7.70 (m, 12H, Ar–H). dC (100 MHz, CDCl3) 16.1 (1C, CH3),
38.4 (1C, –CH2–CO, C-7), 49.1 (1C, C-13), 50.7 (1C, N–CH2–,
C-6), 63.7 (1C, –CH2–, bridged), 118.7 (1C, Ar, C-2), 126.2 (2C,
Ar, C-1, C-10), 126.3 (1C, Ar, C-40), 127.5 (3C, Ar, C-3, C-4,
C-13a), 128.2 (1C, Ar, C-12), 128.3 (2C, Ar, C-20, C-60), 129.3
(3C, Ar, C-30, C-50, C-9), 133.7 (1C, Ar, C-11), 134.1 (1C, Ar,
C-8a), 143.1 (1C, Ar, C-12a), 143.6 (1C, Ar, C-10), 150.6 (1C, Ar,
C-4a), 202.4 (1C, C¼O, C-8). Anal. calc. for C24H21NO (339):
C 84.95, H 6.19, N 4.12. Found: C 85.11, H 6.04, N 4.31%.
4,8,8-Trimethyl-13-phenyl-6,7,8,13-tetrahydro-5H-
5,13-methano-dibenzo[b,e]azonine (10b)
Yellow needles; 88 %; mp 118–1198C (acetone). nmax (KBr)/
cmꢀ1 3055, 2985, 1580, 1490, 1450, 1430, 1385, 1030 750. dH
(400 MHz, CDCl3) 1.34 (s, 6H, 2CH3), 1.73 (t, 2H, J 7.4, 7CH2),
2.36 (s, 3H, CH3), 3.34 (t, 2H, J 7.4, 6CH2), 4.13 (d, Ha, J 9.3,
bridged CH2), 4.48 (approx. t, Hb, J 9.3, bridged CH2), 6.63–
7.65 (m, 12H, Ar–H). dC (100 MHz, CDCl3) 16.1 (1C, –CH3),
27.0 (1C, C-8), 29.2 (2C, –C(CH3)2), 37.1 (1C, N–CH2–, C-6),
44.5 (1C, –CH2–, C-7), 64.0 (1C, –CH2–, bridged), 50.2 (1C,
C-13), 118.7 (1C, Ar, C-2), 125.6 (1C, Ar, C-9), 125.9 (1C, Ar,
C-10), 126.2 (2C, Ar, C-1, C-11), 126.3 (1C, Ar, C-40), 127.5
4-Methyl-14-phenyl-6,7,8,9,14-pentahydro-5H-5,14-
methano-dibenzo[b,e]azecin-9-one (11a)
White crystals; 91 %; mp 95–968C (benzene). nmax (KBr)/
cmꢀ1 3065, 2950, 1740, 1585, 1463, 1440, 1385, 1275, 1130,

412
H. A. K. Abd El-Aal, A. A. Khalaf, and A. M. A. El-Khawaga
(3C, Ar, C-3, C-4, C-13a), 127.9 (1C, Ar, C-12), 128.3 (2C, Ar,
C-20, C-60), 129.3 (2C, Ar, C-30, C-50), 142.4 (1C, Ar, C-12a),
143.6 (1C, Ar, C-10), 150.6 (1C, Ar, C-4a), 150.9 (1C, Ar, C-8a).
Anal. calc. for C26H27N (353): C 88.38, H 7.64, N 3.96. Found:
C 88.58, H 7.49, N 3.92 %.
References
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Reddish viscous oil; 90 %; n2D5 1.592. nmax (film)/cmꢀ1 3066,
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(approx. q, 2H, J 6, CH2), 4.13 (d, Ha, J 9.3, bridged CH2),
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dC (100 MHz, CDCl3) 16.1 (1C, –CH3), 36.9 (1C, N–CH2–,
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145.6 (2C, Ar, C-8a, C-12a), 150.6 (1C, Ar, C-4a). Anal. calc.
for C36H31N (477): C 90.56, H 6.49, N 2.93. Found: C 90.42,
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Pale-yellow crystals; 92 %; mp 94–958C (methanol). nmax
(KBr)/cmꢀ1 3065, 2935, 1590, 1565, 1485, 1440, 1375, 1285,
1040, 746. dH (400 MHz, CDCl3) 1.34 (s, 6H, 2CH3), 1.46 (t, 2H,
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J 7.4, CH2), 1.57 (approx. quint., J 7.4, CH2), 2.35 (s, 3H,
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4.42 (q, Hb, J 9.3, bridged CH2), 6.62–7.63 (m, 12H, Ar–H). dC
(100 MHz, CDCl3) 16.1 (1C, –CH3), 22.7 (1C, –CH2–, C-7),
29.5 (2C, –C(CH3)2), 29.6 (1C, C-9), 43.2 (1C, –CH2–, C-8),
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143.6 (1C, Ar, C-10), 150.6 (1C, Ar, C-4a), 150.9 (1C, Ar, C-9a).
Anal. calc. for C27H29N (367): C 88.28, H 7.90, N 3.81. Found:
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(400 MHz, CDCl3) 1.53 (quint., 2H, J 7.4, CH2), 2.18 (t, 2H,
J 7.4, 8CH2), 2.35 (s, 3H, CH3), 3.38 (t, 2H, J 7.4, 6CH2), 4.24
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6.50–8.10 (m, 22H, Ar–H). dC (100 MHz, CDCl3) 16.1 (1C,
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