Synthesis of 5,6-dihydrobenz[c]acridines: a comparative study

Article abstract of DOI:10.1016/j.tet.2008.11.049

5,6-Dihydrobenz[c]acridines were synthesized by the reaction of 1-chloro-3,4-dihydro-2-naphthaldehyde with aromatic amines under three different conditions:a.Thermolysis of 1-chlorovinyl-(N-aryl)imines prepared from 1-chloro-3,4-dihydro-2-naphthaldehyde.b

Full text of DOI:10.1016/j.tet.2008.11.049

Tetrahedron 65 (2009) 811–821
Contents lists available at ScienceDirect
Tetrahedron
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Synthesis of 5,6-dihydrobenz[c]acridines: a comparative study
,
,
b,
*
P. Karthikeyan a b, A. Meena Rani a, R. Saiganesh a, K.K. Balasubramanian a , S. Kabilan
*
a Shasun Research Centre, No. 27, Vandaloor–Kelambakkam Road, Keelakottaiyur, Chennai 600 048, India
b Department of Chemistry, Annamalai University, Annamalai Nagar 608 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 May 2008
Received in revised form 12 November 2008
Accepted 17 November 2008
Available online 24 November 2008
5,6-Dihydrobenz[c]acridines were synthesized by the reaction of 1-chloro-3,4-dihydro-2-naph-
thaldehyde with aromatic amines under three different conditions:
a. Thermolysis
of
1-chlorovinyl-(N-aryl)imines
prepared
from
1-chloro-3,4-dihydro-2-
naphthaldehyde.
b. Acid catalyzed cyclization of 1-(N-aryl)amino-3,4-dihydro-2-naphthaldehydes.
c. Thermolysis of N-arylenaminoimine hydrochlorides derived from 1-chloro-3,4-dihydro-2-naph-
thaldehyde in DMF medium.
All the three approaches exclusively yielded only 5,6-dihydrobenz[c]acridines and not the isomeric 7,8-
dihydrobenzo[k]phenanthridines.
The structures of these products have been unambiguously established by detailed NMR spectral study
and by independent synthesis as well as by single crystal XRD study.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
quinolines, benzacridines,17 etc. Of the several methods available in
the literature for the synthesis of quinoline derivatives, the one
Quinolines and their derivatives are under constant in-
vestigation of the medicinal chemists in view of their profound
range of biological activities viz., antimalarial,1 anti-bacterial,2 anti-
asthmatic,3 anti-hypertensive,4 anti-inflammatory,5 etc. The qui-
nolone structural moiety is present in most of the anti-bacterials
introduced in the recent past namely, Nalidixic acid,6 Norfloxacin,7
Ciprofloxacin,8 Ofloxacin,9 etc. In addition to their pharmaceutical
applications, quinolines have also been employed in the study of
bioorganic and bioorganometallic processes.10
The general approach for the synthesis of quinolines is based
upon either Skraup,11 Doebner–von Miller,12 Combes13 or Fried-
laender14 reaction. These reactions are still used for the manufac-
ture of many quinoline derivatives and active pharmaceutical
ingredients. Despite their versatility and simplicity, these reactions
suffer from disadvantages like harsh conditions, difficult work-up
procedures and lack of regioselectivity in the case of meta-
substituted anilines. The recent progress in the synthesis of quin-
olines has been reviewed by Kouznetsov et al.15
based on the thermal transformation of N-arylenaminoimine
hydrochlorides is particularly useful for the preparation of 2-
substituted, 2,3-disubstituted and 2,3-annulated quinolines. The
first report of such a reaction was by Julia in 1950,18 followed by
that of Lloyd and Gagan.19 The solution thermolysis of N-arylen-
aminoimine hydrochloride 2, obtained by the reaction of
b-
chlorovinyl aldehyde 1 and arylamine as shown in Scheme 1, was
found to be selective and led only to quinoline 3. The formation
of 2,3-disubstituted quinolines 3 in preference to the other regio-
isomeric 3,4-disubstituted quinolines 4 was rationalized by Lloyd
et al. based on the conformational considerations and steric factors
for the two modes of cyclization.
Since then, numerous reports have appeared in the literature on
the thermolysis of N-arylenaminoiminium salts and this subject
has been recently reviewed.20 A facile synthesis of condensed
benzopyrano[4,3-b]quinolines 7 by neat pyrolysis of N-arylenami-
noimine hydrochlorides 6 derived from 4-chlorobenzopyran-3-
21
carbaldehyde 5 was reported
(Scheme 2). The structures
In recent years, many publications have appeared on the
chemistry of
proposed for benzopyranoquinolines 7 were based on the earlier
b-halo-a,b
-unsaturated aldehydes16 especially their
work of Jacquignon.22
use as synthons in the synthesis of condensed heterocycles like
An interesting and useful Buchwald amination of 1-chloro-3,4-
dihydro-2-naphthaldehyde 9 with 2,5-dimethoxyanline yielding
1-(N-2,5-dimethoxy aryl)amino-3,4-dihydro-2-naphthaldehyde 11c
was described recently by Hesse and Kirsch.23 The authors have
reported that the reaction of 1-chloro-3,4-dihydro-2-naphthaldehyde
* Corresponding authors.
E-mail address: kkb@shasun.com (K.K. Balasubramanian).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.049

812
P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
R2
R2
R1
R2
R2
R1
R
H2N
CHO
R
R1
DMF/POCl3
R1
Cl
NH HN
Cl
N
O
R
R
3
2
1
R-ArNH3+ Cl-
R1
R2
R
N
4
Scheme 1.
O
investigation by additional spectroscopic studies, which have been
performed and delineated later in this paper.
O
2Ar-NH2
CHCl3 / RT
H
Another publication that prompted us to disclose our own find-
ings is a recent report on the chemoselective arylamination of 1-
bromo-3,4-dihydro-2-naphthaldehyde25 followed byacid catalyzed
cyclization of 1-(N-aryl)amino-3,4-dihydro-2-naphthaldehydes 11.
With these background, we have conducted a detailed study on the
thermal cyclization of N-arylenaminoimine hydrochloride salts 19,
1-chlorovinyl-(N-aryl)imines 10 and also on acid catalyzed cycliza-
tion of 1-(N-aryl)amino-3,4-dihydro-2-naphthaldehydes 1120,26
(Scheme 5).
CHO
.HCl
NH
N
Cl
R
6
R
5
O
O
N
NH2
O
2. Results and discussion
CHO
+
NaOEt
N
EtOH
2.1. Synthesis of 1-chlorovinyl-(N-aryl) imines and it’s
thermal cyclization
R
O
R
R
R = H
8
7
Normally, the b-chlorovinyl aldehydes are very reactive towards
Scheme 2.
aromatic amines and they invariably lead to the formation of the N-
arylenaminoimine hydrochlorides even at room temperature. We
had earlier reported27 a simple and facile synthesis of a number of
1-chlorovinyl-(N-aryl)imines of 4-chloro-3-formyl-2H[1]benzo-
pyran and thiopyrans (Scheme 6) by reacting the carboxaldehydes,
9 and 2,5-dimethoxyanilinewith caesiumcarbonate intoluene (90 ꢀC,
20 h, absence of the Pd catalyst) yielded hitherto unknown 7,8-dihy-
drobenz[k]phenanthridine 12c (direct electrocyclization product) and
dimethoxy 1-chloro-3,4-dihydro-2-naphthaldehyde imine 10c, in
a ratio of 3:1, respectively (Scheme 3). In addition, they observed the
formation of the same cyclized product 12c when the reaction was
performed in isopropanol under reflux conditions for 4 h (Scheme 3).
Surprisingly, there was no citation about the plausible alternate
structure 13c, arising by an alternate mode of cyclization which has
a rich precedence in the literature.17
viz. 4-chlorobenzopyran-3-carboxaldehyde
5
and 4-chloro-
thiobenzopyran-3-caboxaldehyde 20, with aromatic primary
amines (dichloromethane, 0–5 ꢀC, 2 h). Irradiation of 21 and 22 in
methanol afforded benzopyrano [4,3-b]quinoline 7 and benzo-
thiopyrano[4,3-b]quinoline 23, respectively, in rather low yield
(Scheme 7) while in the presence of a base no reaction was
observed upon irradiation.
We had observed that under aforesaid conditions 1-chloro-3,4-
dihydro-2-naphthaldehyde 9 (Scheme 7, Table 1) did not furnish
the corresponding 1-chlorovinyl-(N-aryl)imines 10 but instead
yielded N-arylenaminoimine hydrochlorides 19. However, when
the reaction was carried out in ethanol at 0–5 ꢀC for 1–1.5 h it
resulted in the selective formation of 1-chlorovinyl-(N-aryl)imines
10 in good yields.
Literature survey for the synthesis of quinolines by thermal cy-
clization of the N-arylenaminoimine hydrochlorides and also for
direct cyclization of 1-chloro-3,4-dihydro-2-naphthaldehyde17 with
anilines revealed that the C2 carbon of the quinoline formed stems
from the
b carbon of the b-chlorovinylaldehyde and not from the
aldehydic carbon as one would normally expect out of six-electron
cyclization. No exception to this mode of cyclization has been
recorded so far. In line with this observation, thermal cyclization of
the N-arylenaminoimines hydrochloride derived from 6-methoxy-
tetralonewould have furnished only 5,6-dihydrobenz[c]acridines 17
and not 7,8-dihydrobeno[k]phenanthridines 1824 (Scheme 4) as
reported. In this regard, a study on the cyclization of 1-(N-2,5-
dimethoxy aryl)amino-3,4-dihydro-2-naphthaldehyde 11c would
have shed some light in deducing the structure of this product.
In view of this conjecture, structure 12c assigned for the cyclized
product looked less probable and warranted a more thorough
It is worth mentioning here that there are only a very few
reports available in the literature on the selective formation of 1-
chlorovinyl-(N-aryl)imines by the reaction of 1-chloro-3,4-dihy-
dro-2-naphthaldehyde 9 with naphthylamine.28 However, the
reaction of 1-chloro-3,4-dihydro-2-naphthaldehyde 9 with aryl-
amines yielded only the corresponding N-arylenaminoimine hy-
drochlorides and not the 1-chlorovinyl-(N-aryl)imines.29 A recent
report30 on the reaction of
b-chloroacroleins with 2-aminophenol
in DMF to yield the condensed quinolines clearly confirms the
highly reactive nature of the aldehydes. It was proposed that the

P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
813
H3CO
OCH3
N
Cl
N
OCH3
H3CO
10c
12c
i
OCH3
OCH3
NH2
Cl
H3CO
NH
CHO
ii
+
N
H3CO
OCH3
CHO
OCH3
13c
11c
9
iii
H3CO
OCH3
N
Cl
N
OCH3
+
H3CO
12c
10c
Scheme 3. Reagents and conditions: (i) 1 equiv 9, 5 equiv 2,5-dimethoxyaniline, isopropanol, reflux, 4 h; (ii) 1 equiv 9, 1 equiv 2,5-dimethoxyaniline, 3 mol % Pd(OAc)2, 4 mol %
BINAP, 1.3 equiv Cs2CO3, dry toluene, argon, 90 ꢀC, 3 h; (iii) 1 equiv 9, 1 equiv 2,5-dimethoxyaniline, 1.3 equiv Cs2CO3, dry toluene, argon, 90 ꢀC, 20 h.
reactions proceed through the intermediacy of the 1-chlorovinyl-
(N-aryl)imines. In this context, our observation on the selective
reaction of arylamines with the b-chloroacroleins to form the 1-
chlorovinyl-(N-aryl)imines in a few specified solvents/reaction
conditions is worth mentioning.
The cyclization of 1-chlorovinyl-(N-aryl)imines 10 to the cor-
responding benz[c]acridines 13 has also been accomplished by
heating in DMF at 140 ꢀC for 1–1.5 h. Similarly, the reaction of
1-chloro-3,4-dihydro-2-naphthaldehyde 9 with 1-naphthylamine
in ethanol afforded 1-chlorovinyl-(N-aryl)imines 24, which on
heating in DMF (140 ꢀC, 4 h) yielded 5,6-dihydrobenz[c,h]acridine
25 as shown in Scheme 8.
We have studied the cyclization of 1-chlorovinyl-(N-aryl)imines
10 under different conditions viz. in refluxing DMF, in N-methyl-
pyrrolidone at 140 ꢀC and in refluxing chlorobenzene (Scheme 7).
The conversion to 5,6-dihydrobenz[c]acridines 13 was accom-
plished under all these conditions except in refluxing chloroben-
zene. It is interesting to note that a normal six-electron cyclization of
this potential electrocyclic system to give 7,8-dihydrobenz[k]-
phenanthridine 12 was not observed. The formation of the 5,6-
dihydrobenz[c]acridine proceeds probably through the initial
hydrolysis of the 1-chlorovinyl-(N-aryl)imines due to the in-
advertent presence of moisture to generate a small amount of the
aromatic primary amine, which in a subsequent reaction with the
1-chlorovinyl-(N-aryl)imines leads to the formation of the N-aryl-
enaminoimine hydrochloride. The N-arylenaminoimine hydro-
chloride cyclizes to give the 5,6-dihydrobenz[c]acridine and 1 equiv
of aromatic primary amine, which leads to the propagation of the
cycle of reactions. When the progress of this reaction was moni-
tored by TLC, it revealed the formation of the red coloured
NH2
R
R
Cl
HN
O
CHO
R
DMF
POCl3
N
.HCl
H3CO
H3CO
H3CO
16
15
14
250 °C
R
R
N
N
H3CO
H3CO
18
17
Scheme 4.

814
P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
NH2
R1
+
R3
CHO
R2
Cl
9
Buchwald amination
Imination
enamination
R1
R3
HCl
N
R1
R3
CHO
R1
NH
R3
R2
NH
R1
Cl
N
R2
R2
R3
R2
10
19
11
Thermolysis
R3
R2
N
R3
R2
N
R1
R1
13
12
R1
R2
R3
a
b
c
H
CH3
H
H
OCH3
H
OCH3
H
OCH3
d
e
H
H
Cl
H
H
H
Scheme 5.
N-arylenaminoimine 19 as a transient intermediate and its sub-
sequent conversion to the cyclized product. This transformation
does not take place in DMF containing potassium carbonate.
The structures of all these cyclized products have been un-
equivocally established as 5,6-dihydrobenz[c]acridines 13 (Table 2)
as discussed below.
structure 12c and strongly supported the alternative 13c (Fig. 1). Of
particular significance is the considerable deshielding of the H7
proton in the case of 13c (
13b ( 7.8).
d 8.32) in comparison to those of 13a and
d
Further support in favour of the 5,6-dihydrobenz[c]acridine
structure was provided by the proton NMR spectrum of N-oxide 26.
Although the reported23 melting point and proton NMR spectral
data of 12c were identical to those of our product derived from
the cyclization of 10c, a detailed multinuclear analysis of this
product by HH COSY, HSQC, HMBC and NOE clearly ruled out
The two doublets at
d 8.5 (H-1) and d 8.0 (H-11) observed in the
proton NMR spectrum of 13a underwent a significant deshielding
upon conversion to N-oxide 26 and appeared at d 9.5 (H-1) and d 8.5
(H-11), respectively (Scheme 9).
R
X
Cl
H2N
R
CHO
Cl
X
N
hv
MeOH
N
X
CH2Cl2
0-5 °C
R
5
X = O
7
X = O
20 X = S
21 X = O
22 X = S
23 X = S
R= H, OCH3, CH3, Cl
Scheme 6.

P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
815
NH2
R1
+
CH2Cl2 / 0-5 °C
R3
R2
N
R3
R3
R2
CHO
Cl
N
R2
EtOH / 0-5 °C
90 min
Cl
R1
R1
9
12
CH2Cl2 / RT
10
.HCl
N
R3
R2
DMF/
140 °C
C6H5Cl
NMP/140 °C
R3
R2
NH
R1
R1
19
N
R3
R2
R1
13
R1
R2
R3
a
H
CH3
H
H
OCH3
b
c
H
OCH3
H
OCH3
d
e
H
H
Cl
H
H
H
Scheme 7.
Table 1
Synthesis of 1-chlorovinyl-(N-aryl)imines 10a–e
(Table 3, Scheme 10). Similarly, naphthylamino aldehyde 27 was
prepared (Scheme 11). Heating these 1-(N-aryl)amino-3,4-dihydro-
2-naphthaldehydes 11 in DMF containing catalytic amount of
p-toluenesulfonic acid at 140 ꢀC for 1 h furnished the correspond-
ing 5,6-dihydrobenz[c]acridines 13 in moderate to good yields
(Table 4). Similarly, cyclization of naphthylamino aldehyde 27
yielded dihydroacridine derivative 25 (Scheme 11).
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
1
2
3
4
5
10a
10b
10c
10d
10e
H
H
OCH3
H
H
CH3
OCH3
H
Cl
H
H
H
OCH3
H
78
75
80
90
75
92–94
82–84
84–86
140–142
72–73
H
Though the cyclization of the 1-(N-aryl)aminoaldehydes derived
by the reaction of
b-bromovinylaldehydes and arylamines is
2.2. Synthesis of 1-(N-aryl)amino aldehydes and it’s thermal
conversion to 5,6-dihydrobenz[c]acridines
known,25 it should be noted that the cyclization was carried out in
trifluoroaceticacid as solvent for 10–12 h and the product was
isolated by preparative thin layer chromatography. An independent
synthesis of 13c was reported31 by reacting 2-amino-3,6-dime-
The assigned structure 13c was further confirmed by an in-
dependent synthesis. Buchwald amination of 1-chloro-3,4-dihy-
dro-2-naphthaldehyde 9 with aromatic amines in toluene as
described by an earlier report23 for 2,5-dimethoxyaniline (Cs2CO3,
Pd(OAc)2, rac-BINAP, 80 ꢀC, 2 h) yielded the corresponding 1-aryl-
amino-3,4-dihydro-2-naphthaldehydes 11 in moderate yields
thoxybenzaldehyde with
shown in Scheme 12.
The melting point and proton NMR spectral data of products
obtained from the thermal cyclization of 10c and 11c were identical
with those reported,31 further corroborating the assigned structure.
a-tetralone under basic conditions as
NH2
EtOH
0-5 °C/ 90 min
DMF/ pTSA
140 °C
N
+
Cl
N
CHO
Cl
9
24
80%
25
87%
Scheme 8.

816
P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
Table 2
2.3. Synthesis of symmetrical enaminoimines and their
thermal studies
Synthesis of 5,6-dihydrobenz[c]acridines 13a–e
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
Adopting the procedure of an earlier published work21 for
an analogous system, reaction of 1-chloro-3,4-dihydro-2-naph-
thaldehyde 9 with a few aromatic amines (2 equiv) in CHCl3 at
room temperature for 3 h yielded the corresponding N-arylena-
minoimine hydrochlorides 19 (Scheme 14 and Table 5). All these
enaminoimines underwent a smooth cyclization when heated in
1
2
3
4
5
13a
13b
13c
13d
13e
H
H
OCH3
H
H
CH3
OCH3
H
Cl
H
H
H
OCH3
H
H
78
90
85
90
80
78–80
112–114
166–168
100–102
68–70
9
8
7
4
1
5
10
11
3
2
6
7
6
12
1
H3CO
N
N
OCH3
5
12
8
9
2
4
OCH3
H3CO 11
3
10
12c
1,4-dimethoxy-7,8-dihydro[k]phenanthridine
Figure 1. Two plausible structures for the cyclization product of 10c.
13c
8,11-dimethoxy-5,6-dihydrobenz[c]acridine
DMF at 140 ꢀC for 1–1.5 h. Quenching the reaction mixture in cold
water directly yielded 5,6-dihydrobenz[c]acridines 13 in good
yields (Table 6). The melting point and spectral data of the product
in the case of the dimethoxy derivative 13c were identical with
those reported.23 However, in the case of 1-naphthylamine the
reaction with 1-chloro-3,4-dihydro-2-naphthaldehyde 9 in CHCl3
yielded only the corresponding 1-chlorovinyl-(N-aryl)imines 25
and not N-arylenaminoimine hydrochloride 29 as shown in Scheme
15. This observation is similar to the one reported earlier.28
Most of the thermolysis of the N-arylenaminoimine hydrochlo-
rides described in the literature have been carried out neat at very
high temperatures ranging from 200 to 270 ꢀC and involved an
extensive work-up procedures. In contrast, our present method
offers a simple and practical route for the synthesis of 5,6-di-
hydrobenz[c]acridines. It is worth mentioning here that the benz-
acridines are found to possess some carcinogenic properties whose
chemistry has been reviewed.35
m-CPBA / CH2Cl2
1
1
N
H
N
H
H
H
O
CH3
CH3
11
11
26
70%
13a
Scheme 9.
Table 3
Synthesis of 1-(N-aryl)amino-2,3-dihydro-2-naphthaldehydes 11a–e
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
1
2
3
4
5
11a
11b
11c
11d
11e
H
H
CH3
OCH3
H
H
H
OCH3
H
H
70
63
65
90
55
82–84
92–94
112–114
138–140
126–128
OCH3
H
The cyclization of 1-chlorovinyl-(N-aryl)imines of 1-chloro-3,4-
dihydro-2-naphthaldehyde provides a simple and alternate route
for the synthesis of 5,6-dihydrobenz[c]acridines (Scheme 7). The
main advantages of this method are shorter reaction time, easy work
Cl
H
H
The proposed structure was further confirmed by single crystal
XRD study (Fig. 2).
NH2
Recently, we came across an interesting publication,33 wherein
it was observed that the Michael type addition of p-anisidine to the
Knoevenagel product 28 furnished 5,6-dihydrobenz[c]acridine 13b
as shown in Scheme 13.
R1
Cs2CO3 / Binap
+
CHO
R1
Pd(OAc)2
R3
CHO
Toluene / 80 °C
NH
Cl
R2
The assignment of this structure was based merely on the an-
alytical data and proton NMR spectral data. Neither the reported
melting point nor the proton NMR spectral data,34 described in this
paper agreed with those of ours. In view of this, we felt that this
compound could be the hitherto unknown 7,8-dihydro-3-
methoxybenzo[k]phenanthridine 12b (Scheme 5, R1¼R3¼H;
R2¼OCH3). However, when we repeated this reaction following
their procedure, we observed that the reaction did not go to com-
pletion even after long hours with 1 equiv of p-anisidine. Use of
2 equiv of p-anisidine led to complete conversion, furnishing
a yellow solid that melted at 110–112 ꢀC, contrary to the melting
point of 248 ꢀC reported by the authors. Also, we observed that the
NMR spectral data differed considerably from those described in
their paper. The melting point, proton NMR data and 13C NMR
spectral data of the product that we obtained were identical in all
respects with those of 13b.
9
R3
R2
11
DMF/140 °C
pTSA
N
R3
R1
R2
13
Scheme 10.

P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
817
O
NH2
H
Cs2CO3
DMF / pTSA
140 °C
NH
N
+
rac BINAP
Pd(OAc)2
Toluene / 80 °C
CHO
Cl
9
27
25
66%
70%
Scheme 11.
Table 4
NH2
Cyclization of 3,4-dihdyro-1-(N-arylamino)-2-naphthaldehydes to 5,6-dihydro-
benz[c]acridines 13a–e
R1
.HCl
R1
CHCl3 / RT
R3
R2
NH
R1
N
+
R3
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
CHO
Cl
R2
R2
1
2
3
13a
13b
13c
H
H
OCH3
CH3
OCH3
H
H
H
OCH3
65
75
62
78–80
112–114
R3
9
166–168
(lit. 160–162)31
100–102
(lit. 102)32
68–70
19
4
5
13d
13e
H
H
Cl
H
H
H
72
75
DMF
140 °C/ 90 min
N
R3
R2
OCH3
NH2
+
R1
H3CO
N
OCH3
13
CHO
O
Scheme 14.
H3CO
13c
Scheme 12.
Table 5
Synthesis of N-arylenaminoimine hydrochlorides 19a–e
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
1
2
3
4
5
19a
19b
19c
19d
19e
H
H
OCH3
H
H
CH3
OCH3
H
Cl
H
H
H
OCH3
H
H
81
68
d
157–159
147–149
d
80
75
168–169
142–144
Table 6
Cyclization of N-arylenaminoimine hydrochlorides to 5,6-dihydrobenz[c]acridines
13a–e
Entry
Product
R1
R2
R3
Yield (%)
Mp (ꢀC)
1
2
3
4
5
13a
13b
13c
13d
13e
H
H
OCH3
H
H
CH3
OCH3
H
Cl
H
H
H
OCH3
H
H
50
60
d
78–80
112–114
d
75
70
100–102
68–70
Figure 2. ORTEP diagram of compound 13c with 50% probability.
OCH3
Cl
Cl
CN
N
CHO
CN
p-anisidine
CH3OH / 6h
CO2C2H5
CO2C2H5
Piperidine
13b
28
9
Scheme 13.

818
P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
NH2
CHCl3
RT
DMF / pTSA
140 °C
N
+
CHO
Cl
N
Cl
9
24
65%
25
CHCl3 / RT
55%
.HCl
NH
N
29
Scheme 15.
Table 7
column chromatography. The determined melting points are un-
corrected. Yields refer to chromatographically and spectroscopi-
cally (1H NMR) homogeneous materials, unless otherwise stated. 1H
NMR spectra were recorded on 300 MHz spectrometer. 13C NMR
spectra were recorded at 75 MHz spectrometer with complete
proton decoupling and calibrated using residual undeuterated
solvent as an internal reference. IR spectra were recorded on an
FTIR spectrometer. High-resolution mass spectra (HRMS) were
recorded on an electrospray mass spectrometer at Indian Institute
of Technology Madras, Chennai 600 036, and Indian Institute of
Sciences, Bangalore. Elemental analysis was done using Thermo
Finnigan Flash EA 1112 elemental analyzer.
A comparison of the three routes to the synthesis of 5,6-dihydrobenz[c]acridines
Entry Product Yield of 5,6-dihydro benzacridines (%)
Mp (ꢀC)
From 1-
chlorovinyl-
From 1-(N-aryl)-
amino-2,3-dihydro- enaminoimine
From N-aryl
(N-aryl)imines 2-naphthaldehydes hydrochlorides
1
2
3
4
5
6
13a
13b
13c
13d
13e
25
78
90
85
90
80
87
65
75
62
72
75
66
50
60
d
75
70
d
78–80
112–114
166–168
100–102
68–70
152–154
up and isolation of the product. As 5,6-dihydrobenz[c]acridines are
easily dehydrogenated to benz[c]acridines,36,17c the three routes
that we have outlined in this work provide an easy access to avariety
of benz[c]acridines. Comparison of the yields of 5,6-dihy-
drobenz[c]acridines by these three routes is shown in Table 7.
Among these routes, the cyclization of 1-chlorovinyl-(N-aryl) imines
using DMF appears to be the best in terms ease of preparation and
yield. Also, it does not require the use of metal catalyst or the ligands.
4.1.1. Typical experimental procedure for 1-chlorovinyl-
(N-aryl)imines 10a–e and 24
To a stirred solution of 1-chloro-3,4-dihydro-2-naphthaldehyde
(1.0 g, 5.19 mmol) in ethanol (5 mL) containing catalytic amount of
p-TSA at 0–5 ꢀC was dropwise added a solution of arylamine
(5.7 mmol) in ethanol (5 mL). The product was filtered after 1.5 h
and recrystallized from hexane.
4.1.2. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-p-tolylamine 10a
3. Conclusion
Yellow solid (78% yield), mp 92–94 ꢀC; Rf¼0.69 (EtOAc/hex-
anes, 2:8); IR (KBr): 761, 818, 960, 1036, 1111, 1261, 1351, 1501,
To conclude the acid catalyzed solution thermolysis of the
N-arylenaminoimine hydrochlorides, the 1-chlorovinyl-(N-aryl)-
imines and the 1-(N-aryl)amino-3,4-dihydro-2-naphthaldehydes,
all yielded the same 5,6-dihydrobenz[c]acridines in moderately
good yields. The present methods offer practical and scalable routes
for the synthesis of a wide variety of condensed quinolines. We had
also attempted to bridge certain anomalies in the literature with
sufficient evidences. Further work on this involving the benzo-
pyrano, benzothiopyrano and coumarino compounds is ongoing.
1561, 1574, 1900, 2356, 2833, 2892, 2943, 3060 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
(m, 5H), 728–7.30 (m, 2H), 7.77–7.80 (m, 1H), 8.89 (s, 1H); 13C
NMR (75 MHz, CDCl3): 21.0, 23.7, 27.4, 121.0, 125.4, 126.7,
d 2.36 (s, 3H), 2.88–2.97 (m, 4H), 7.12–7.20
d
127.3, 129.5, 129.7, 132.7, 132.8, 136.2, 137.7, 138.2, 149.5, 157.6;
HRMS m/z calculated for C18H16ClN [MþH]: 282.1050, found:
282.1047.
4.1.3. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-(4-methoxyphenyl)-amine 10b
4. Experimental
Yellow solid (75% yield), mp 82–83 ꢀC; Rf¼0.76 (EtOAc/hexanes,
4.1. General methods
2:8); IR (KBr): 758, 834, 1034, 1244, 1296, 1503, 1606, 1886, 2830,
2955, 3007 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
2.88–2.97 (m, 4H),
3.83 (s, 3H), 6.93 (d, 2H, J¼8.8 Hz), 7.19–7.31 (m, 5H), 7.77–7.80 (m,
1H), 8.90 (s, 1H); 13C NMR (75 MHz, CDCl3):
23.7, 27.4, 55.4, 114.3,
All reactions were carried out in oven-dried apparatus using dry
solvents under anhydrous conditions. Commercial grade solvents
were distilled and dried according to the literature procedures.
Analytical TLC was performed on commercial plates coated with
silica gel GF254 (0.25 mm). Silica gel (230–400 mesh) was used for
d
122.5, 125.3, 126.7, 127.3, 129.4, 132.7, 132.9, 137.2, 138.1, 144.9,
156.3, 158.5; HRMS m/z calculated for C18H16ClNO [MþH]:
298.0914, found: 298.0913.

P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
819
4.1.4. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-(2,5-dimethoxyphenyl)-amine 10c
1437, 1511, 1554, 1588, 1605, 1625, 1886, 2730, 2803, 2916,
3024 cmꢁ1; 1H NMR (300 MHz, CDCl3):
2.33 (s, 3H), 2.48–2.54 (m,
d
Yellow solid (80% yield), mp 84–86 ꢀC; Rf¼0.65 (EtOAc/hexanes,
2:8); IR (KBr): 765, 841, 948, 964, 1042, 1110, 1220, 1261, 1299, 1339,
2H), 2.82–2.87 (m, 2H), 6.79 (d, 2H, J¼8.3 Hz), 6.94–7.00 (m, 3H),
7.18 (d, 1H, J¼7.9 Hz), 7.22–7.26 (m, 2H), 9.40 (s, 1H), 11.85 (br, 1H);
1446, 1501, 1583, 2361, 2830, 2905 cmꢁ1
;
1H NMR (300 MHz,
13C NMR (75 MHz, CDCl3):
d 20.8, 23.5, 30.0, 109.7, 123.0, 125.6,
CDCl3):
d
2.88–3.01 (m, 4H), 3.81 (s, 3H), 3.85 (s, 3H), 6.63 (d, 1H,
128.0, 128.8, 129.5, 130.0, 133.6, 138.7, 140.7, 153.1, 189.7. HRMS
J¼8.8 Hz), 6.73 (dd, 1H, J¼2.8 and 8.6 Hz), 6.86 (d, 1H, J¼8.8 Hz),
calculated for C18H17NO [MþH]: 264.1388, found: 264.1381.
7.19–7.22 (m, 1H), 7.27–7.33 (m, 2H), 7.77–7.80 (m, 1H), 8.89 (s, 1H);
13C NMR (75 MHz, CDCl3):
d
23.7, 27.3, 55.7, 56.5, 106.8, 111.1, 112.6,
4.2.2. Synthesis of 1-(4-methoxy-phenylamino)-3,4-dihydro-
naphthalene-2-carbaldehyde 11b
125.5, 126.7, 127.4, 129.7, 132.7, 132.8, 138.3, 142.5, 146.6, 154.0,
159.7; HRMS m/z calculated for C19H18ClNO2 [MþH]: 328.1104,
found: 328.1101.
Red colour solid (63% yield); mp 92–94 ꢀC; Rf¼0.56 (EtOAc/
hexanes, 2:8); 1H NMR (300 MHz, CDCl3):
d 2.48–2.55 (m, 2H),
2.81–2.86 (m, 2H), 3.76 (s, 3H), 6.73 (d, 2H, J¼8.8 Hz), 6.85 (d, 2H,
4.1.5. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-(4-chlorophenyl)-amine 10d
J¼8.6 Hz), 6.92–6.98 (m, 1H), 7.15 (d, 1H, J¼7.7 Hz), 7.22–7.26 (m,
2H), 9.38 (s, 1H), 11.13 (br, 1H); 13C NMR (75 MHz, CDCl3):
d 23.5,
Yellow solid (90% yield); mp 140–142 ꢀC; Rf¼0.86 (EtOAc/hex-
anes, 2:8); IR (KBr): 765, 833, 961,1087,1160, 1182,1243,1262,1350,
30.2, 55.4, 109.0, 114.2, 124.7, 125.6, 128.0, 128.9, 130.0, 134.4, 140.9,
153.5, 156.5, 189.4; HRMS m/z calculated for C18H17NO2 [MþH]:
280.1337, found: 280.1334.
1452, 1575, 1593, 1896, 2348, 2834, 2896, 2948 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
1H), 7.28–7.34 (m, 3H), 7.36–7.38 (m, 1H), 7.78–7.81 (m, 1H) 8.85 (s,
1H); 13C NMR (75 MHz, CDCl3):
23.5, 27.2, 122.3, 125.4, 126.7,
127.3, 129.1, 129.7, 131.6, 132.3, 132.6, 138.1, 138.6, 150.4, 158.6;
HRMS m/z calculated for C17H13Cl2N [MþH]: 302.0503, found:
302.0501.
d 2.92 (s, 4H), 7.13–7.16 (m, 2H), 7.21–7.23 (m,
4.2.3. Synthesis of 1-(2,5-methoxy-phenylamino)-3,4-dihydro-
naphthalene-2-carbaldehyde 11c
Red crystalline solid (65% yield); mp 112–114 ꢀC; Rf¼0.48
(EtOAc/hexanes, 2:8); IR (KBr): 700, 718, 778, 853, 1005, 1086, 1141,
1234, 1391, 1442, 1490, 1555, 1602, 1619, 1936, 2832, 2940 cmꢁ1; 1H
d
NMR (300 MHz, CDCl3):
d 2.51–2.55 (m, 2H), 2.81–2.86 (m, 2H),
4.1.6. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-phenylamine 10e
3.54 (s, 3H), 3.78 (s, 3H), 6.26 (d, 1H, J¼3.0 Hz), 6.50 (dd, 1H), 6.78
(d, 1H, J¼6.0 Hz), 6.89–7.05 (m, 1H), 7.24–7.29 (m, 3H), 9.50 (s, 1H),
Yellow solid (75% yield); mp 72–73 ꢀC; Rf¼0.69 (EtOAc/hexanes,
11.13 (br, 1H); 13C NMR (75 MHz, CDCl3):
d 23.2, 29.7, 55.6, 56.3,
108.1, 109.2, 112.1, 125.7, 127.8, 127.9, 129.4, 130.1, 131.7, 140.2, 145.1,
152.1, 153.3, 190.0.
2:8); IR (KBr): 761, 823, 961, 1182, 1263, 1451, 1482, 1577, 1600,
2894 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
2.89–2.99 (m, 4H), 7.19–
7.25 (m, 4H), 7.29–7.31 (m, 2H), 7.38 (t, 2H), 7.77–7.80 (m, 1H), 8.88
(s, 1H); 13C NMR (75 MHz, CDCl3):
23.7, 27.4, 121.1, 125.5, 126.2,
d
4.2.4. Synthesis of 1-(4-chloro-phenylamino)-3,4-dihydro-
naphthalene-2-carbaldehyde 11d
126.8,127.4,129.1,129.7,132.6,132.8,138.1,138.2,152.2,158.5; HRMS
m/z calculated for C17H14ClN [MþH]: 268.0893, found: 268.0897.
Yellow crystalline solid (90% yield); mp 138–140 ꢀC; Rf¼0.60
(EtOAc/hexanes, 2:8); IR (KBr): 774, 782, 848, 1002, 1023, 1143,
1168,1219,1252,1319,1367,1440, 1511,1555,1577, 1600,1631, 2829,
4.1.7. Synthesis of (1-chloro-3,4-dihydro-naphthalen-2-
ylmethylene)-naphthalen-1-ylamine 2428a
Yellow solid (80% yield); mp 107–109 ꢀC (lit. 110–111 ꢀC);
Rf¼0.89 (EtOAc/hexanes, 2:8); IR (KBr): 765, 828, 960, 1077, 1149,
1265, 1393, 1435, 1559, 1592, 1958, 2375, 2927, 3014 cmꢁ1; 1H NMR
2924, 3412 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 2.51–2.55 (m, 2H),
2.82–2.87 (m, 2H), 6.81 (d, 2H, J¼8.6 Hz), 6.97–7.04 (m, 1H), 7.14 (d,
3H, J¼8.5 Hz), 7.27 (d, 2H, J¼3.9 Hz), 9.44 (s, 1H), 11.67 (br, 1H); 13C
NMR (75 MHz, CDCl3):
d 23.3, 29.7, 111.0, 123.8, 125.8, 128.1, 128.4,
(300 MHz, CDCl3):
d
2.95–3.00 (m, 2H), 3.09–3.14 (m, 2H), 7.08 (d,
128.5, 128.9, 130.3, 140.1, 140.4, 152.1, 190.6; HRMS m/z calculated
for C17H14ClNO [MþH]: 284.0842, found: 284.0846.
1H, J¼7.3 Hz), 7.30–7.33 (m, 2H), 7.44–7.53 (m, 3H), 7.72 (d, 1H,
J¼8.2 Hz), 7.80–7.86 (m, 2H), 8.31–8.34 (m, 1H), 8.98 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d
23.8, 27.4, 112.8, 123.8, 125.5, 125.7, 126.0,
4.2.5. Synthesis of 1-(phenylamino)-3,4-dihydro-naphthalene-2-
carbaldehyde 11e
126.1, 126.4, 126.8, 127.4, 127.6, 128.9, 129.7, 132.8, 133.9, 138.2,
149.2, 158.3.
Yellow solid (75% yield); mp 126–128 ꢀC; Rf¼0.68 (EtOAc/hex-
anes, 2:8); IR (KBr): 735, 778, 1188, 1256, 1385, 1416, 1491, 1556,
4.2. Typical experimental procedure for the preparation of
1580, 1605, 2831, 2922, 3025 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
1-(N-aryl)amino-3,4-dihydro-2-naphthaldehydes 11a–e and 27
d 2.57–2.68 (m, 2H), 2.75–2.79 (m, 2H), 6.67–6.83 (m, 1H), 6.93–
6.97 (m, 2H), 7.10–7.15 (m, 3H), 7.17–7.20 (m, 3H), 9.36 (s, 1H), 11.67
(br, 1H); 13C NMR (75 MHz, CDCl3): 23.4, 29.7, 110.4, 122.8, 123.8,
125.7, 128.0, 128.8, 128.9, 130.1, 140.5, 141.5, 152.6, 190.2; HRMS m/z
calculated for C17H14ClN [MþH]: 250.1232, found: 250.1236.
To a solution of 1-chloro-3,4-dihydro-2-naphthaldehyde (1.0 g,
5.19 mmol) in dry toluene (15 mL) were added Cs2CO3 (7.69 mmol),
Pd(OAc)2 (2.67 mmol) and racemic BINAP (0.16 mmol) under ni-
trogen atmosphere. The resultant mixture was heated to 80 ꢀC and
stirred for 1 h. A solution of aromatic amine (5.19 mmol) in dry
toluene (5 mL) was then added dropwise to the above mixture.
When the reaction was complete by TLC, the mixture was cooled to
room temperature and filtered through Celite bed. The filtrate was
then concentrated in vacuo to give the crude product, which was
purified by column chromatography (Basic alumina, 20% EtOAC/
Hexanes).
4.2.6. Synthesis of 1-(naphthalene-1-ylamino)-3,4-dihydro-
naphthalene-2-carbaldehyde 27
Red solid (70% yield); mp 108–110 ꢀC; Rf¼0.69 (EtOAc/hexanes,
2:8); IR (CHCl3): 791, 1016, 1145, 1175, 1241, 1267, 1358, 1386, 1557,
1581, 1602, 1624, 1672, 2838, 2927 cmꢁ1 1H NMR (300 MHz,
;
CDCl3):
d 2.57–2.61 (m, 2H), 2.88–2.93 (m, 2H), 6.77 (d, 1H,
J¼7.3 Hz), 6.83 (t, 1H, J¼8.1 Hz), 6.99 (d, 1H, J¼7.7 Hz), 7.16–7.27 (m,
3H), 7.52–7.62 (m, 3H), 7.87 (d, 1H, J¼7.3 Hz), 8.39 (d, 1H, J¼8.1 Hz),
4.2.1. Synthesis of (1-p-tolylamino)-3,4-dihydro-naphthalene-2-
carbaldehyde 11a
Yellow solid (70% yield); mp 82–84 ꢀC; Rf¼0.69 (EtOAc/hexanes,
2:8); IR (KBr): 743, 773, 814,1006,1143,1178,1231,1322,1336,1388,
9.50 (s, 1H), 12.18 (br, 1H); 13C NMR (75 MHz, CDCl3):
d 24.0, 30.4,
111.2, 121.8, 122.8, 125.0, 125.6, 126.1, 126.9, 128.4, 128.6, 128.8,
129.3, 130.5, 134.7, 138.0, 140.8, 154.5, 190.8; HRMS m/z calculated
for C21H17NO [MþH]: 300.1388, found: 300.1380.

820
P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
4.3. Typical experimental procedure for the preparation of
N-arylenaminoimine hydrochlorides 19a–e
hydrochlorides (1.0 g, 1 equiv) in DMF (10 mL)/p-TSA was refluxed
(140 ꢀC) for 1–1.5 h. The reaction mixture was cooled to room
temperature and poured over crushed ice. Filtering and drying
yielded solids that were purified by column chromatography (10%
EtOAc/hexane) to give the title compounds.
A mixture of 1-chloro-3,4-dihydro-2-naphthaldehyde (1.0 g,
5.19 mmol) and arylamine (10.3 mol) in CHCl3 (10 mL) was stirred
at room temperature for 3.5 h. The precipitated red solid was fil-
tered and recrystallizied in ethylacetate.
4.4.1. Synthesis of 9-methyl-5,6-dihydrobenz[c]acridine 13a
White crystalline solid; yield: 78% by imine route, 65% by ami-
noaldehyde route, 50% enaminoimine HCl route; mp 78–80 ꢀC;
Rf¼0.72 (EtOAc/hexanes, 2:8); IR (KBr): 740, 763, 832, 917, 1018,
1040, 1140, 1255, 1291, 1375, 1442, 1496, 1599, 2361, 2848, 2938,
4.3.1. Synthesis of 1-[(p-methylphenyl)amino]-2-[((p-methyl
phenyl)imino)methyl]-3,4-dihydro-naphthalene
hydrochloride 19a
Red solid (81% yield); mp 170 ꢀC; Rf¼0.82 (EtOAc/hexanes, 2:8);
IR (KBr): 756, 833, 1012, 1093, 1210, 1342, 1480, 1578, 1608, 1637,
3024, 3420, 3735, 3839 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 2.33 (s,
3H), 2.95–3.00 (m, 2H), 3.06–3.10 (m, 2H), 7.25 (d, 1H, J¼6.7 Hz),
;
2922, 3276, 3436 cmꢁ1 1H NMR (300 MHz, CDCl3 and one drop
7.31–7.45 (m, 3H), 7.48 (s, 1H), 7.79 (s, 1H), 8.01 (d, 1H, J¼8.5 Hz),
DMSO-d6):
d
2.03 (s, 3H), 2.31 (s, 3H), 2.79 (s, 4H), 6.95 (d, 2H,
8.55 (d, 1H, J¼7.3 Hz); 13C NMR (75 MHz, CDCl3):
d 21.6, 28.4, 28.8,
J¼8.2 Hz), 7.01–7.10 (m, 5H), 7.21 (d, 1H, J¼7.3 Hz), 7.30 (t, 2H), 7.48
125.8, 125.9, 127.2, 127.8, 129.0, 129.4, 130.5, 130.9, 133.0, 134.8,
135.8, 139.2, 146.2, 152.5; HRMS m/z calculated for C18H15N [MþH]:
246.1282, found: 246.1285. Anal. Calcd for C18H15N: C, 88.13; H,
6.16; N, 5.71. Found: C, 88.16; H, 6.39; N, 5.90.
(s, 1H), 7.74 (d, 2H, J¼7.9 Hz), 8.99 (d, 1H, J¼12.6 Hz), 11.49 (s, 1H),
11.94 (br, 1H); 13C NMR (75 MHz, CDCl3):
d 20.7, 20.8, 23.6, 28.9,
109.0,119.0,122.8,126.0,127.8,128.4,129.6,129.9,132.3,134.9,136.3,
136.6, 139.1, 143.6, 150.2, 161.2. Anal. Calcd for C25H25ClN2: C, 77.20;
H, 6.48; Cl, 9.12; N, 7.20. Found: C, 77.15; H, 6.41; Cl, 9.05; N, 7.39.
4.4.2. Synthesis of 9-methoxy-5,6-dihydrobenz[c]acridine 13b
White crystalline solid; yield: 90% by imine route, 75% by ami-
noaldehyde route, 60% by enaminoimine HCl route; mp 112–114 ꢀC;
Rf¼0.66 (EtOAc/hexanes, 2:8); IR (KBr): 761, 828, 910, 1023, 1184,
1226, 1288, 1363, 1378, 1467, 1492, 1610, 2836, 2942, 3056 cmꢁ1; 1H
4.3.2. Synthesis of 1-[(p-methoxyphenyl)amino]-2-[((p-methoxy
phenyl)imino)methyl]-3,4-dihydro-naphthalene
hydrochloride 19b17b
Red solid (68% yield); mp 156 ꢀC; Rf¼0.52 (EtOAc/hexanes, 2:8);
IR (KBr): 771, 813, 1020, 1093, 1265, 1431, 1546, 1615, 2853, 3144,
NMR (300 MHz, CDCl3): d 2.95–3.01 (m, 2H), 3.07–3.12 (m, 2H),
3.92 (s, 3H), 7.02 (d, 1H, J¼2.1 Hz), 7.25–7.35 (m, 3H), 7.41 (t, 1H),
3350 cmꢁ1 1H NMR (300 MHz, CDCl3 and one drop DMSO-d6):
;
7.81 (s, 1H), 8.03 (d, 1H, J¼9.2 Hz), 8.51 (d, 1H, J¼7.3 Hz); 13C NMR
d
2.74–2.76 (m, 2H), 2.88–2.90 (m, 2H), 3.75 (s, 6H), 6.74–6.92 (m,
6H), 7.02–7.08 (m, 3H), 7.32–7.38 (m, 3H), 7.56 (d, 2H, J¼8.6 Hz),
8.83 (s, 1H); 13C NMR (75 MHz, CDCl3):
23.2, 28.6, 55.2, 108.8,
(75 MHz, CDCl3): d 28.4, 28.8, 55.5, 104.7, 121.1, 125.6, 127.2, 127.8,
128.8, 129.2, 130.8, 132.6, 134.8, 138.9, 143.6, 151.1, 157.6. HRMS m/z
calculated for C18H15NO [MþH]: 262.1232, found: 262.1237.
d
114.3, 114.4, 114.4, 119.1, 120.6, 123.9, 125.9, 128.3, 128.5, 128.7, 131.6,
135.1, 142.7, 151.2, 156.6, 157.8. Anal. Calcd for C25H25ClN2O2: C,
71.33; H, 5.99; N, 6.65. Found: C, 71.19; H, 6.03; N, 6.67.
4.4.3. Synthesis of 8,11-dimethoxy-5,6-dihydrobenz[c]acridine 13c
Yellow crystalline solid; yield: 85% by imine route, 62% by
aminoaldehyde route; mp 166–168 ꢀC (lit. 160–162 ꢀC); Rf¼0.66
(EtOAc/hexanes, 2:8); IR (KBr): 721, 778, 794, 1099, 1259, 1384,
4.3.3. Synthesis of 1-[(p-chlorophenyl)amino]-2-
[((p-chlorophenyl)imino)methyl]-3,4-dihydro-
1459, 1602, 2835, 2931, 3737 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
naphthalene hydrochloride 19d
d 2.97–3.02 (m, 2H), 3.11–3.16 (m, 2H), 3.96 (s, 3H), 4.06 (s, 3H), 6.71
Redsolid(80%yield);mp186 ꢀC; Rf¼0.78(EtOAc/hexanes, 2:8);IR
(KBr): 721, 745, 779, 967, 967,1088,1197,1234,1338,1489,1538,1601,
1628, 2847, 3035, 3257 cmꢁ1; 1H NMR (300 MHz, CDCl3 andonedrop
(d, 1H, J¼8.3 Hz), 6.89 (d, 1H, J¼8.3 Hz), 7.25 (d, 1H, J¼6.8 Hz), 7.32–
7.42 (m, 2H), 8.32 (s, 1H), 8.62 (d, 1H, J¼7.3 Hz); 13C NMR (75 MHz,
CDCl3): d 28.4, 28.9, 55.8, 56.4, 103.4, 106.7, 121.1, 126.4, 127.2, 127.8,
DMSO-d6):
d
2.70–2.74 (m, 2H), 2.86–2.88(m, 2H), 7.04 (t,1H), 7.14 (d,
128.8, 129.6, 130.2, 134.7, 139.2, 139.9, 148.5, 149.7, 152.6; HRMS m/z
calculated for C19H17NO2 [MþH]: 292.1337, found: 292.1339.
2H, J¼8.7 Hz), 7.20–7.30 (m, 6H), 7.37 (m,1H), 7.59 (s,1H), 7.87 (d, 2H,
J¼8.5 Hz), 9.17 (s, 1H); 13C NMR (75 MHz, CDCl3):
d 23.8, 28.8, 110.8,
120.7, 122.9, 123.9, 126.3, 127.1, 128.7, 129.2, 129.9, 130.1, 131.9, 133.0,
137.5, 140.3, 143.8, 151.1, 161.7. Anal. Calcd for C23H19Cl3N2: C, 64.28;
H, 4.46; Cl, 24.75; N, 6.52. Found: C, 64.33; H, 4.52; Cl, 24.62; N, 6.51.
4.4.4. X-ray crystallographic data of 13c
Structure was solved by direct methods (SIR92). Refinement was
by full-matrix least-squares procedures on F2 by using SHELXL-97.
Crystal system: monoclinic, space group: P21, cell parameters:
4.3.4. Synthesis of 1-phenylamino-2-(phenylimino)methyl-3,4-
dihydro-naphthalene hydrochloride 19e
a¼8.858(3), b¼17.538(6), c¼9.726(3) Å,
a
¼90.00ꢀ,
b
¼108.208(7)ꢀ,
g
¼90.00ꢀ, cell volume¼1435.2(8) Å3, and Z¼4. The intensity data
Red solid (75% yield); mp 148 ꢀC; Rf¼0.78 (EtOAc/hexanes, 2:8);
were collected on a Bruker SMART CCD area detector with graphite
IR (KBr): 685, 752, 777, 963, 1162, 1235,1302, 1341, 1422, 1481, 1546,
monochromated Mo
m
Ka
(l
¼0.71073 Å) radiation. F(000)¼616,
1633, 2819, 3048, 3259 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
2.44–
¼0.087 mmꢁ1. Total number ls parameters¼201 for all 2519 data
2.46 (m, 2H), 2.67–2.70 (m, 2H), 6.65 (t,1H), 6.90 (t,1H), 7.01 (t, 2H),
7.10–7.17 (m, 3H), 7.21–7.24 (m, 5H), 7.98 (d, 2H, J¼8.1 Hz), 9.11 (d,
2H, J¼14.6 Hz), 11.62 (s, 1H), 12.21 (d, 1H, J¼14.6); 13C NMR
(CCDC no. 693163). Crystallographic data (excluding structure fac-
tors) for the structures in this paper have been deposited to the
Cambridge Crystallographic Data Centre as supplementary publi-
cation. Copies of these data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
þ44 1223 336033 or via e-mail: deposit@ccdc.cam.ac.uk or via
www.ccdc.cam.ac.uk/conts/retrieving.html.
(75 MHz, CDCl3): d 24.9, 29.0, 111.8, 119.0, 122.4, 124.6, 125.5, 126.3,
127.3, 128.3, 128.8, 129.2, 130.4, 132.4, 138.3, 141.8, 144.0, 150.2,
160.8. Anal. Calcd for C23H21ClN2: C, 76.55; H, 5.87; Cl, 9.82; N, 7.76.
Found: C, 76.35; H, 5.84; Cl, 10.04; N, 7.76.
4.4. Typical experimental procedure for the preparation of
4.4.5. Synthesis of 9-chloro-5,6-dihydrobenz[c]acridine 13d
5,6-dihydrobenz[c]acridines 13a–e and 25
White crystalline solid; Yield: 90% by imine route, 72% by ami-
noaldehyde route, 75% enaminoimine HCl; mp 100–102 ꢀC (lit.
102 ꢀC); Rf¼0.88 (EtOAc/hexanes, 2:8); IR (KBr): 725, 835, 914,1075,
1136, 1289, 1342, 1394, 1484, 1598, 1934, 2848, 2940, 3028,
A stirred solution of 1-chlorovinyl-(N-aryl)imines or 1-(N-aryl)-
amino-3,4-dihydro-2-naphthaldehydes or N-arylenaminoimine

P. Karthikeyan et al. / Tetrahedron 65 (2009) 811–821
821
3047 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
2.98–3.03 (m, 2H), 3.10–
References and notes
3.14 (m, 2H), 7.28 (d, 1H, J¼8.8 Hz), 7.35–7.45 (m, 2H), 7.57 (dd, 1H,
J¼2.3 and 9.0 Hz), 7.72 (d, 1H, J¼2.1 Hz), 7.82 (s, 1H), 8.06 (d, 1H,
J¼9.0 Hz), 8.54 (dd, 1H, J¼1.6 and 7.2 Hz); 13C NMR (75 MHz,
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28.2, 29.2, 125.6, 126.0, 127.3, 128.0,128.4, 129.5, 129.9,
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4.4.6. Synthesis of 5,6-dihydrobenz[c]acridine 13e
White solid; Yield: 80% by imine route, 75% by aminoaldehyde
route, 70% enaminoimine HCl; mp 68–70 ꢀC; Rf¼0.78 (EtOAc/hex-
anes, 2:8); IR (KBr): 737, 769, 861, 912, 951, 1098, 1125, 1290, 1409,
1431, 1456, 1493, 1553, 1598, 1814, 2949, 3036 cmꢁ1 1H NMR
;
(300 MHz, CDCl3): d 2.95–3.00 (m, 2H), 3.06–3.11 (m, 2H), 7.22–7.25
(m, 1H), 7.35 (t, 1H), 7.38–7.47 (q, 2H), 7.63 (t, 1H), 7.71 (d, 1H, J¼
7.9 Hz), 7.87 (s, 1H), 8.12 (d, 1H, J¼8.4 Hz), 8.55 (d, 1H, J¼8.2 Hz); 13C
NMR (75 MHz, CDCl3):
d 28.4, 28.5, 126.0, 126.1, 126.9, 127.3, 127.9,
128.0,128.6,129.5,129.7,130.6,133.7,134.8,139.5,147.7,153.4; HRMS
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4.4.7. Synthesis of 5,6-dihydro-dibenz[c,h]acridine 25
White solid; yield: 87% by imine route, 66% by aminoaldehyde
route; mp 154–156 ꢀC (lit. 154–155 ꢀC); Rf¼0.75 (EtOAc/hexanes,
2:8); IR (KBr): 735, 748, 799, 819, 949, 1103, 1295, 1402, 1428, 1490,
1594, 1821, 2833, 2903, 2931, 3044; 1H NMR (300 MHz, CDCl3):
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d
3.00–3.05 (m, 2H), 3.12–3.17 (m, 2H), 7.24–7.29 (m,1H), 7.37 (t,1H,
J¼7.2 Hz), 7.47 (t, 1H, J¼7.3 Hz), 7.60–7.75 (m, 4H), 7.86–7.91 (m,
2H), 8.77 (d, 1H, J¼7.5 Hz), 9.48 (d, 1H, J¼8.1 Hz); 13C NMR (75 MHz,
CDCl3):
d 28.3, 28.4, 124.4, 124.9, 125.6, 125.9, 126.7, 127.1, 127.2,
127.6, 127.7, 127.9, 129.4, 130.7, 131.8, 133.4, 134.0, 135.1, 139.0, 145.1,
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4.5. Typical experimental procedure of 9-methyl-5,6-
dihydrobenz[c]acridine 12-oxide 26
A solution of the 9-methyl-5,6-dihydrobenz[c]acridine (500 mg,
2.04 mmol) and meta-chloroperbenzoic acid (3.06 mmol) in chlo-
roform (2.5 mL) was stirred overnight at room temperature, and
the solvent was removed. The crude product was purified by col-
umn chromatography (30% EtOAc/hexane) to give compound 26.
Pale yellow solid (70% yield); mp 150–152 ꢀC; Rf¼0.32 (EtOAc/
hexanes, 2:8); IR (KBr): 736, 749, 776, 820, 894, 1073, 1211, 1266,
1329, 1488, 1577, 1620, 2843, 2902, 2944, 3062 cmꢁ1
;
1H NMR
(300 MHz, CDCl3): 2.52 (s, 3H), 2.87–2.91 (m, 2H), 2.96–3.00 (m,
d
2H), 7.26–7.27 (m, 1H), 7.29–7.43 (m, 3H), 7.52 (d, 2H, J¼9.6 Hz),
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8.71 (d, 1H, J¼8.6 Hz), 9.60 (dd, 1H, J¼1.3 and 8.8 Hz); 13C NMR
(75 MHz, CDCl3):
d
21.3, 29.3, 30.1, 120.0, 122.5, 126.1, 126.4, 127.4,
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128.4, 128.5, 129.3, 130.0, 131.6, 133.6, 138.4, 139.9, 140.3, 140.4;
HRMS m/z calculated for C18H15NO [MþH]: 262.1232, found:
262.1234 (MþH). Anal. Calcd for C18H15N: C, 82.73; H, 5.79; N, 5.36;
O, 6.12. Found: C, 82.85; H, 6.02; N, 5.57; O, 5.55.
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Acknowledgements
The authors wish to express their thanks to the Chief Scientific
Officer and the Management of Shasun Research Centre for their
support and encouragement during the entire course of this work.
Also thanks are due to analytical division for their help in carrying
out NMR spectral analysis of these compounds and the librarian for
arranging the reprints of published articles.
29. Pan, D.; Kar, G. K.; Ray, J. K.; Lin, J.-M.; Amin, S.; Chantrapromma, S.; Fun, H.-K.
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34. NMR data 1H NMR (CDCl3): dppm¼2.88 (t, J¼2.5 Hz, 2H, CH2ring), 3.22 (t, J¼
2.5 Hz, 2H, CH2ring), 3.78 (s, 3H, OCH3), 6.98–7.78 (m, 8H, Ar–H); 13C NMR
(CDCl3): dppm¼27.8, 28.3, 54.8, 104.8, 121.3, 126.2 (2C), 127.0 (2C), 128.4, 129.1
(2C), 134.4, 138.8 (2C), 142.0 (2C), 157.0.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.11.049.
35. Motohashi, N.; Emrani, J.; Meyer, R.; Kawase, M. Org. Prep. Proced. Int. 1993, 261.
36. Andre, J.; Jacquignon, P.; Buu-Hoi, N. P.; Perin, F. J. Heterocycl. Chem. 1971, 8, 529.