A Simple and Practical Approach To The Dibenzo (C, F) Thiazolo (3,2-A) Azepines: A Novel Fused Tetracyclic Azepine System

PAPER
A Simple and Practical Approach to the Dibenzo[c,f]thiazolo[3,2-a]azepines:

A Novel Fused Tetracyclic Azepine System
Synthesi ofDibenzo[c,f]thiazol [3,2-a] zepines Palma,*a Nelson Galeano,a Ali Bahsasb
Alirio
a
Laboratorio de Sntesis Orgnica, Escuela de Qumica, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Colombia
Fax +57(76)349069; E-mail: [email protected]
b
Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Qumica, Universidad de los Andes, Mrida 5101, Venezuela
Received 7 September 2009; revised 15 December 2009
Abstract: A novel set of functionalized dibenzo[c,f]thiazolo[3,2a]azepines, which is a new ring system, were successfully synthesized in a four-step protocol starting from readily available substituted N-allyl-N-benzylanilines. The synthesis of the title
compounds was accomplished through cyclocondensation of morphanthridines with mercaptoacetic acid. Morphanthridines were
prepared by selective oxidation of dihydromorphanthridines with
pyridinium chlorochromate in dichloromethane. The dihydromorphanthridines were obtained by acid-catalyzed intramolecular
FriedelCrafts alkylation of substituted 2-allyl-N-benzylanilines,
which in turn, were prepared from N-allyl-N-benzylanilines by aromatic amino-Claisen rearrangement. The structural elucidation of
all synthesized compounds by high resolution NMR is also reported.
no prior literature reports that describe the fusion of the

dibenz[b,e]azepine nucleus to a thiazolidin-4-one ring,
also a core structure in important synthetic molecules with
significant biological activity, including antibacterial, antifungal, anticancer, anti-HIV, antiparasitic, and antipsychotic activities among others.8
R1
N
N
R2
Me
II
Key words: amino-Claisen rearrangement, intramolecular Friedel

Crafts alkylation, 2-allyl-N-benzylanilines, dihydromorphanthridines, dibenzo[c,f]thiazolo[3,2-a]azepines
N
The dibenz[b,e]azepine ring is a commonly observed

structural moiety in the molecular structures of important
fused tetracyclic azepines with pharmacological potential,
as shown by the examples in Figure 1. Thus, mianserin
(Tolvon) and its N-substituted derivatives I as well as mirtazapine (azamianserin, Remeron) analogue II are well
documented in the literature as antidepressants1 and antiserotoninergic agents.2 2-(Aminoalkyl)-2,3,3a,8-tetrahydrodibenz[c,f]oxazolo[2,3-a]azepine derivatives III were
synthesized and evaluated as potent and selective 5HT2A/2C receptor antagonists with oral activity and,
therefore, could be considered as potential anxiolytic/antidepressant agents.3 Some of these compounds may also
be used as therapeutic agents in the treatment or the prevention of cardiovascular disorders or gastrointestinal disorders.3,4 Epinastine (IV) was initially patented as an antiallergenic and antihistaminergic agent,5 but it is also used
for pain treatment and prophylaxis, especially, for chronic
or inflammation-induced pain, in particular, in migraine.6
The unique structural features and biological properties of
tetracyclic azepine derivatives have resulted in considerable synthetic efforts to develop efficient methods for the
synthesis of bioactive derivatives in which the tricyclic
dibenz[b,e]azepine ring is fused at the N5C6 bond with
different heterocycles.1a,24,5b,d,e,7 Surprisingly, there are
SYNTHESIS 2010, No. x, pp 000A000Lxx. 201
Advanced online publication: xx.xx.2010
DOI: 10.1055/s-0029-1218674; Art ID: M05209SS
Georg Thieme Verlag Stuttgart New York
N
O
N
H2N
R2
( )n
IV
N
R1
III
Figure 1
azepines
Molecular structures of some bioactive-fused tetracyclic
Among the classical methodologies, the intramolecular

FriedelCrafts alkylation has been particularly useful in
synthetic organic chemistry, since this reaction results in
the construction of an extra ring by generation of a new
CC bond,9 including the central azepine ring of the
dibenz[b,e]azepine system.3,7g,j,10 In this context, several
years ago our laboratory became interested in using the
acid-catalyzed intramolecular FriedelCrafts alkylation
of ortho-amino-substituted allylarenes V to prepare
dihydrodibenz[b,e]azepines VI and dihydrobenzo[e]naphth[b]azepines VII (Scheme 1).11
On the other hand, knowing that the cyclocondensation
reaction of an imine and a-mercaptoalkanoic acid is the
most convenient method for the preparation of many thiazolidin-4-one derivatives,12 and having in our hands an
expedient synthetic route to build the dihydrodibenz[b,e]azepine ring, we decided to extend our investigation to the synthesis of the novel compounds with the
general structure 5 as shown retrosynthetically in
Scheme 2.
PAPER
A. Palma et al.
R2
R2
R1
R1
R1
R2 ref. 11a
ref. 11b
N
VI
O
VII
Scheme 1
ortho-Amino-substituted allylarenes in the construction of dihydrodibenz[b,e]azepine and dihydrobenzo[e]naphth[b]azepine rings

R2
R2
R1
R1
R3
R2
R1
R3
N
N
S
Scheme 2
R3
Retrosynthetic analysis of title compounds 5
To the best of our knowledge, the facile construction of

this new tetraheterocyclic system using the classical cyclocondensation reaction of an imine and mercaptoacetic
acid in the morphanthridine series has not been previously
explored. It is the purpose of this paper to describe the
successful synthesis of novel tetrahydrodibenzo[c,f]thiazolo[3,2-a]azepine derivatives 5, using as the main transformations the intramolecular FriedelCrafts alkylation of
substituted 2-allyl-N-benzylanilines and boron trifluoridediethyl ether complex catalyzed cyclocondensation
reaction of morphanthridines and mercaptoacetic acid.
The synthesis of the tricyclic precursors, 6,11-dihydro5H-dibenz[b,e]azepines 3, was achieved using our previously reported multistep reaction protocol (Scheme 3).11a
Initially, the key intermediates, substituted 2-allyl-N-benzylanilines 2, were easily obtained by thermal-induced
aromatic amino-Claisen rearrangement of the corresponding N-allyl-N-benzylanilines 1 using our previous reported experimental conditions.13 Thus, heating synthetically
available substituted N-allyl-N-benzylanilines 1 with 1.5
equiv of boron trifluoridediethyl ether complex at 138
145 C for 35 hours produced rearranged compounds
2ai, which after chromatographic purification were isolated as viscous maroon oils in good to excellent yields
(7488%). The yields were not significantly affected by
the nature and positions of substituents on either benzene
ring of precursors 1.
R1
As previously reported,11a under acidic conditions the allylic fragment of the rearranged products 2 can be used as
potential electrophilic center to be exploited in the construction of the dihydrodibenz[b,e]azepine ring. Taking
into account this result, we initially examined the intramolecular cyclization of 2a using various Brnsted acids in
excess, including sulfuric (95%), polyphosphoric, 4-toluenesulfonic, trifluoroacetic, tetrafluoroboric (54% HBF4
in Et2O), and perchloric (70%) acids, for varying temperatures and times.
TLC and GC-MS analysis indicated formation of the expected dihydromorphanthridine 3a with several of these
acids and the best results were obtained with sulfuric and
perchloric acids. We found that the progress of the reaction became very slow when carried out with polyphosphoric acid; heating the reaction mixture at 100110 C
for 1.5 hours gave 3a together with complex mixtures of
undesirable products. Control experiments also indicated
that cyclization reaction did not take place when carried
out with 4-toluenesulfonic acid, trifluoroacetic acid in
acetic acid, or tetrafluoroboric acid, even at high temperatures (100120 C) and for long reaction times (14 h);
in each case unchanged starting material was recovered.
Based on these preliminary results, we chose both sulfuric
and perchloric acids to perform the intramolecular cyclization of the remaining 2-allyl-N-benzylanilines 2bi.
Under the reaction conditions employed, all the 2-allyla-
R1
R2
ii
i
N
N
R2
1ai
a R1 = R2 = R3 = H;
d R1 = Me, R2 = R3 = H;
g R1 = Cl, R2 = H, R3 = Me;
R2
3
R3
N
H
3ai
2ai
b R1 = F, R2 = R3 = H;
e R1 = OMe, R2 = R3 = H;
h R1 = R2 = Me, R3 = H;
R1
c R1 = Cl, R2 = R3 = H;
f R1 = R3 = H, R2 = Me;
i R1 = R3 = Me, R2 = H
Scheme 3 Synthesis of dihydromorphanthridines 3. Reagents and conditions: (i) BF3OEt2 (1.5 equiv), 138145 C, 35 h, 7488% ; (ii) 95%
H2SO4, 7090 C, 560 min or 70% HClO4, 85120 C, 3060 min (see Table 1).
Synthesis 2010, No. x, AL
Thieme Stuttgart New York
PAPER
Synthesis of Dibenzo[c,f]thiazolo[3,2-a]azepines
nilines were transferred, through a 7-exo-trig cyclization

route, to the corresponding substituted dihydromorphanthridines in moderate to good yields (Table 1).
Table 1 Preparation of Dihydromorphanthridines 3 by Intramolecular FriedelCrafts Alkylation of Substituted 2-Allylanilines 2 with

Sulfuric and Perchloric Acids
The obtained results indicated that the cyclization reaction

can take place over a wide range of temperatures. In general, we find it convenient to carry out the reaction at a
temperature range from 70 to 90 C in the presence of sulfuric acid, and at a temperature of 85 to 120 C with perchloric acid. The required time for the reaction (560 min)
may also vary widely, depending on the reaction temperature, the nature of the substituents, and, notably, the acid
used. We also found that the conditions employed for the
cyclization of 2e with concentrated sulfuric acid led to the
formation of the expected dihydromorphanthridine 3e in
very low quantities (5%) along with a large amount of inseparable byproducts. In this case, it is probable that the
increased nucleophilicity of the benzene ring in 2e by the
presence of both the methoxy and the amino groups facilitates the sulfonation of the activated benzene instead of
the intramolecular alkylation of the benzylic benzene; it is
also probable that the double bond of the allylic fragment
undergoes sulfonation in the presence of sulfuric acid to
form the respective sulfonic acid derivatives.14 However,
using perchloric acid instead of sulfuric acid increased the
yield of 3e to 65%, especially when the reaction was carried out at 8590 C for 60 minutes (Table 1, entry 10).
Entry
It should also be noted that in the cases of 2g and 2i with

a methyl group in the meta position of the benzylic fragment, the cyclization occurred with complete regioselectivity to give only one of the two possible regioisomers, 8substituted dihydromorphanthridines 3g and 3i (Table 1,
entries 13, 14, 17, and 18). The complete regioselectivity
observed with 2g and 2i could be readily explained by the
differences in the stabilities of the two possible Wheland
intermediates A and B, that can be formed during the cyclization process (Figure 2).15 The generation of the intermediate B is more difficult because of the unfavorable
steric interactions between the hydrogen atom at C10a and
the methyl substituent at C10, an interaction that is not
present in the intermediate A.
H
H
R
N+
H
A
N+
H
B
Figure 2 Wheland complexes A and B as potential intermediates in

the intramolecular FriedelCrafts alkylation of 2g and 2i
In general, the use of sulfuric acid as a promoter of the intramolecular FriedelCrafts alkylation of all the key intermediates 2 examined, with the exception of 2e, proved to
be more efficient in terms of yields, lower temperatures,
and shorter reaction times, compared to perchloric acid.
The structures of all the 6,11-dihydro-5Hdibenz[b,e]azepines 3 obtained were determined by one-
Acid
Time
(min)
2a
H2SO4
30
7075
3a
75
2a
HClO4
60
105110
3a
70
2b
H2SO4
30
7580
3b
65
2b
HClO4
45
115120
3b
73
2c
H2SO4
30
7580
3c
62
2c
HClO4
45
115120
3c
68
2d
H2SO4
3d
75
2d
HClO4
30
100105
3d
72
2e
H2SO4
6070
3e
5b
10
2e
HClO4
60
8590
3e
65
11
2f
H2SO4
90
3f
73
12
2f
HClO4
30
3f
70
13
2g
H2SO4
90
3g
75
14
2g
HClO4
30
8590
2g
66
15
2h
H2SO4
90
3h
73
16
2h
HClO4
30
3h
68
17
2i
H2SO4
90
3i
84
18
2i
HClO4
60
110
3i
75
a
b
Temp
(C)
Product Yielda
(%)
90
25
100105
100105
Yields are for isolated, chromatographically pure products.

Plus byproducts.
and two-dimensional NMR spectroscopy. The assignments of all the signals to individual H and C atoms (see
experimental) have been made from their chemical shift
values, coupling constants, and confirmed on the basis of
COSY, HMQC and HMBC spectra as well as by comparing with the reference spectra of previously reported analogues.11a
Having in hand the required tricyclic precursors 3, we
then turned our attention to the synthesis of their oxidized
analogues 4. Dihydromorphanthridines 3ai were easily
converted into the corresponding morphanthridines 4ai
by oxidation with equimolar amounts of pyridinium chlorochromate in dichloromethane at 0 C (Scheme 4). When
the reactions were complete, usually in 3040 minutes,
the dehydrogenated compounds 4 were isolated by silica
gel column chromatography in excellent yields (8595%)
as high-viscosity yellow oils.
MS spectral data for 4ai were in full agreement with the
expected compounds (see experimental). The IR spectra
displayed absorption bands at ca. 16181609 cm1 characteristic for N=CH stretching vibration (endocyclic imine
group). The 1H NMR spectra showed the same set of sigSynthesis 2010, No. x, AL
PAPER
A. Palma et al.
13
12
R1
10
11
5
3
4
R2
R2
R3
R1
R3
N
H
3ai
14
ii
15
R1
R2
11
12
R3
13
N
4ai
10
13b
4N
S
1
5ai
Scheme 4 Synthesis of title compounds 5. Reagents and conditions: (iii) PCC (1 equiv), CH2Cl2, 0C, 3040 min, 8595%; (ii) DeanStark
trap, HSCH2CO2H (3 equiv), BF3OEt2 (trace), toluene, reflux, 2440 h, 5065%.
nals in the aliphatic region (triplet for H11, d = 3.693.58,

J = 8.0 Hz; multiplet for 12-CH2, d = 1.691.65, and triplet for 13-CH3, d = 0.710.69, J = 7.47.2 Hz) as those reported for 3ai, except for the disappearance of signals
originated from the 6-CHAHB and NH protons. In addition, the appearance in the 1H NMR spectra of a singlet at
d = 8.798.67 as well as a signal at d = 160.6158.1 in the
13
C NMR spectra unambiguously confirmed the formation of the CH=N group.
In the last step of our approach, the construction of the
thiazolidinone ring and. consequently, the formation of
the new tetracyclic system 5 was accomplished through a
cyclocondensation of 4 with a threefold excess of mercaptoacetic acid. The reaction was carried out in dry toluene
at reflux using a DeanStark water separator, and in the
presence of a trace of boron trifluoridediethyl ether complex (Scheme 4). In this way, and after heating 2440
hours, the desired title compounds, dibenzo[c,f]thiazolo[3,2-a]azepines 5ai, were chromatographically isolated in 5065% yields together with significant amounts of
unreacted starting materials (2045%). It is worthy of
note that in the absence of boron trifluoridediethyl ether
the cyclocondensation required longer reaction times
(>60 h) and the yields of the expected compounds dramatically decreased (<20%). Unfortunately, all attempts to
further improve the yields of 5 either by heating in the
presence
of
cyclohexylcarbodiimide
in
dry
tetrahydrofuran16 or by extending the reaction time (60 h)
in the presence of molecular sieves (4 ) in benzene or
toluene were unsuccessful. The construction of the thiazolidinone ring in compounds 5 is assumed to proceed via
initial attack by the sulfur nucleophile to the iminic carbon
activated by boron trifluoridediethyl ether, followed by
intramolecular cyclization between amino and carboxylic
groups with the elimination of a water molecule.
The structure elucidation of the new compounds 5 was
based on spectral data (IR, MS, 1H NMR, and 13C NMR)
and elemental analysis. Thus, the presence in the IR spectra of the characteristic absorption band at about 1711
1690 cm1 associated with a lactam C=O provided the first
evidence for ring closure. In the EI-MS, their molecular
ion peaks of high intensity (3657%) were observed together with their fragment ion peaks M+ SCHCHO
C2H5 as base peaks (see experimental).
The formation of the thiazolidinone ring in 5 was also
clearly evident from the signals around d = 33.933.5,
64.864.4, and 172.1171.6 in the 13C NMR spectra, as-
signed for methylene (C2), methine (C13b) and carbonyl

(C3) carbons, respectively. Furthermore, long range couplings from the proton attached to C13b to C2, C9a, C13a,
and C13 were observed in their HMBC spectra. Additional support was obtained from the 1H NMR spectra, where
the iminic proton (N=CH) signal was absent, but the resonances at d = 6.236.15, 3.993.97, and 3.643.62 attributed to 13b-CH, 2-CHAHB, and 2-CHAHB protons of
the thiazolidin-4-one ring were clearly identified. The two
diastereotopic hydrogens at C2 displayed two signals appearing as doublet (2J = 15.615.2 Hz) or double doublet
(2J = 15.5 Hz and 4Jtrans = 0.7 Hz) for proton H2A, and
double doublet (2J = 15.615.2 Hz and 4Jcis = 2.01.8 Hz)
for proton H2B due to geminal coupling and coupling with
tertiary proton H13b. All the above signals in the 1H and
13
C NMR spectra were fully assigned on the basis of
COSY and HMQC as well as HMBC experiments.
In conclusion, we have successfully extended the classical
cyclocondensation of an imine and mercaptoacetic acid to
the synthesis of previously unknown dibenzo[c,f]thiazolo[3,2-a]azepine derivatives. Our synthetic procedure
proved to be attractive due to its simplicity and of great
practical value; it could provide a new approach to the
synthesis of potential antiparasitic agents against Trypanosoma cruzi and Leishmania chagasi parasites as well as
CNS active molecules in the group of dibenzo[c,f]thiazolo[3,2-a]azepines. Their anxiolytic and anti-parasitic activities are currently investigated and the detailed results
from these studies will be reported in the near future elsewhere.
All the reagents and solvents were purchased from commercial suppliers (Aldrich, Merck), and used without further purification. Analytical TLC was performed on Merck precoated silica gel (60 F254)
plates and column chromatography was accomplished on Merck
Kieselgel 60 70230 mesh (ASTM). Melting points were determined on a MEL-TEMP 1201D capillary apparatus and are uncorrected. IR spectra were recorded on a Nicolet Avatar 360-FTIR
spectrophotometer and referenced to polystyrene standard, using
cells equipped with KBr windows. 1H (400.13 MHz) and 13C NMR
(100.6 MHz) spectra were acquired on a Bruker AM-400 spectrometer using CDCl3 as the solvent and chemical shifts relative to the
solvent peaks used as reference [CDCl3: dH = 7.26, and dC = 77.0].
MS were obtained by electron impact at 70 eV on a HewlettPackard (HP) 5890 A series II Gas Chromatograph interfaced to a
HP 5972 Mass Selective Detector with a HP MS ChemStation Data.
Elemental analyses (C, H, N) were performed on a Perkin-Elmer
2400 Series II analyzer. The synthesis and structural characterization of 2ac and 3ac were previously reported.11a
PAPER
2-Allyl-N-benzylanilines 2; General Procedure
A mixture of N-allyl-N-benzylaniline 1 (0.10 mmol) and BF3OEt2
(0.15 mmol) was heated at 138145 C for 35 h under N2. The
mixture was cooled to r.t. and then it was poured into ice-H2O (30
mL), treated with sat. Na2CO3 soln to pH 8, and extracted with
CH2Cl2 (3 50 mL). The combined organic extracts were dried (anhyd Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by column chromatography (silica gel, heptane
EtOAc, 30:1, 20:1).
2-Allyl-N-benzylaniline (2a)
Time: 3 h; maroon oil; yield: 75%.
IR (KBr): 3439 (NH), 3028 (CH Ar), 1634 (C=C allyl), 1510
(C=C Ar), 914 cm1 (=CH allyl).
1
H NMR (400 MHz, CDCl3): d = 3.37 (d, J = 6.0 Hz, 2 H,

CH2CH=), 4.16 (br s, 1 H, NH), 4.40 (s, 2 H, NCH2), 5.12 (dq,
J = 16.0, 1.6 Hz, 1 H, =CHAHB), 5.17 (dq, J = 10.0, 1.6 Hz, 1 H,
=CHAHB), 6.02 (ddt, J = 16.0, 10.0, 6.0 Hz, 1 H, =CH), 6.69 (dd,
J = 7.2, 0.8 Hz, 1 H, H6), 6.77 (td, J = 7.2, 0.8 Hz, 1 H, H4), 7.13
(dd, J = 7.2, 1.4 Hz, 1 H, H3), 7.18 (td, J = 7.6, 1.4 Hz, 1 H, H5),
7.307.42 (m, 5 H, H2, H3, H4, H5, H6).
13
C NMR (100 MHz, CDCl3): d = 36.5 (CH2CH=), 48.2 (NCH2),

110.7 (C6), 116.3 (=CH2), 117.4 (C4), 123.5 (C2), 127.1 (C5),
127.4 (C2, C6), 127.7 (C4), 128.6 (C3, C5), 129.8 (C3), 136.0
(CH=), 139.5 (C1), 146.1 (C1).
MS (EI, 70 eV): m/z (%) = 223 (35) [M+], 146 (12), 132 (100), 117
(24), 91 (87), 77 (16), 65 (28).
2-Allyl-N-benzyl-4-fluoroaniline (2b)
Time: 4.5 h; maroon oil; yield: 76%.
1

=CHAHB), 5.97 (ddt, J = 18.0, 10.0, 6.4 Hz, 1 H, =CH), 6.56 (dd,
J = 9.0, 5.0 Hz, 1 H, H6), 6.83 (d, J = 3.0 Hz, 1 H, H3), 6.85 (dd,
J = 9.0, 3.0 Hz, 1 H, H5), 7.307.39 (m, 5 H, H2, H3, H4, H5,
H6).
13

111.5 (d, 3JC,F = 10.0 Hz, C6), 113.4 (d, 2JC,F = 20.0 Hz, C3), 116.5
(d, 2JC,F = 20.0 Hz, C5), 116.9 (=CH2), 125.3 (d, 3JC,F = 10.0 Hz,
C2), 127.2 (C4), 127.5 (C2, C6), 128.5 (C3, C5), 135.1 (CH=),
139.3 (C1), 142.3 (C1), 155.6 (d, 1JC,F = 206.1 Hz, C4).
MS (EI, 70 eV): m/z (%) = 241 (23) [M+], 164 (10), 150 (71), 135
(20), 91 (100), 77 (6), 65 (21).
2-Allyl-N-benzyl-4-chloroaniline (2c)
1

=CHAHB), 5.95 (ddt, J = 17.0, 10.0, 6.0 Hz, 1 H, =CH), 6.54 (d,
J = 8.0 Hz, 1 H, H6), 7.06 (d, J = 2.0 Hz, 1 H, H3), 7.08 (dd, J = 8.0,
2.0 Hz, 1 H, H5), 7.307.43 (m, 5 H, H2, H3, H4, H5, H6).
13

111.8 (C6), 116.9 (=CH2), 122.0 (C4), 125.2 (C2), 127.3 (C2, C6),
127.4 (C5), 128.7 (C3), 129.0 (C4), 129.5 (C3, C5), 135.0 (CH=),
139.0 (C1), 144.6 (C1).
MS (EI, 70 eV): m/z (%) = 257 (35Cl, 20) [M+], 180 (7), 166 (26),
151 (4), 131 (40), 91 (100), 65 (26).
2-Allyl-N-benzyl-4-methylaniline (2d)
1
H NMR (400 MHz, CDCl3): d = 2.35 (s, 3 H, 4-CH3), 3.40 (d,

J = 6.0 Hz, 2 H, CH2CH=), 4.42 (s, 2 H, NCH2), 5.18 (dq, J = 18.0,
1.6 Hz, 1 H, =CHAHB), 5.21 (dq, J = 10.0, 1.6 Hz, 1 H, =CHAHB),
6.06 (ddt, J = 18.0, 10.0, 6.0 Hz, 1 H, =CH), 6.65 (d, J = 8.0 Hz, 1
H, H6), 7.0 (br s, 1 H, H3), 7.03 (dd, J = 8.0, 1.2 Hz, 1 H, H5), 7.36
(t, J = 8.0 Hz, 1 H, H4), 7.42 (t, J = 8.0 Hz, 2 H, H3, H5), 7.45 (d,
J = 8.0 Hz, 2 H, H2, H6).
13
C NMR (100 MHz, CDCl3): d = 20.5 (4-CH3), 36.6 (CH2CH=),

48.6 (NCH2), 111.2 (C6), 116.3 (=CH2), 123.9 (C2), 126.7 (C4),
127.2 (C4), 127.5 (C2, C6), 128.1 (C5), 128.7 (C3, C5), 130.8
(C3), 136.3 (=CH), 139.7 (C1), 143.9 (C1).
MS (EI, 70 eV): m/z (%) = 237 (76) [M+], 208 (13), 160 (15), 146
(100), 132 (25), 131 (60), 91 (86), 77 (13).
2-Allyl-N-benzyl-4-methoxyaniline (2e)
1

CH2CH=), 3.78 (s, 3 H, 4-OCH3), 4.35 (s, 2 H, NCH2), 5.13 (dq,
=CHAHB), 6.01 (ddt, J = 17.2, 10.0, 6.0 Hz, 1 H, =CH), 6.63 (d,
J = 8.8 Hz, 1 H, H6), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H, H5), 6.78 (d,
J = 3.0 Hz, 1 H, H3), 7.327.42 (m, 5 H, H2, H3, H4, H5, H6).
13
55.3 (4-OCH3), 111.6 (C5, C6), 116.0 (=CH2), 116.2 (C3), 125.1
(C2), 126.7 (C4), 127.0 (C2, C6), 128.1 (C3, C5), 135.3 (=CH),
139.3 (C1), 139.9 (C1), 151.6 (C4).
MS (EI, 70 eV): m/z (%) = 253 (100) [M+], 224 (3), 176 (6), 162
(72), 148 (8), 147 (21), 91 (75), 65 (15).
2-Allyl-N-(4-methylbenzyl)aniline (2f)
1

6.03 (ddt, J = 17.0, 10.0, 6.0 Hz, 1 H, =CH), 6.73 (d, J = 8.0 Hz, 1
H, H6), 6.80 (td, J = 8.0, 1.0 Hz, 1 H, H4), 7.15 (dd, J = 8.0, 1.0 Hz,
1 H, H3), 7.22 (td, J = 8.0, 1.0 Hz, 1 H, H5), 7.23 (d, J = 8.0 Hz, 2
H, H3, H5), 7.33 (d, J = 8.0 Hz, 2 H, H2, H6).
13

48.1 (NCH2), 110.9 (C6), 116.4 (=CH2), 117.5 (C4), 123.7 (C2),
127.5 (C2, C6), 127.8 (C5), 129.4 (C3, C5), 129.9 (C3), 136.1
(=CH), 136.5 (C1), 136.9 (C4), 146.3 (C1).
MS (EI, 70 eV): m/z (%) = 237 (35) [M+], 208 (8), 146 (7), 132 (71),
118 (17), 117 (12), 105 (100), 91 (8), 79 (13).
2-Allyl-4-chloro-N-(3-methylbenzyl)aniline (2g)
1

5.97 (ddt, J = 17.2, 10.4, 6.0 Hz, 1 H, =CH), 6.58 (d, J = 8.4 Hz, 1
PAPER
A. Palma et al.
H, H6), 7.08 (d, J = 2.4 Hz, 1 H, H3), 7.11 (dd, J = 8.4, 2.4 Hz, 1 H,
H5), 7.177.28 (m, 4 H, H2, H4, H5, H6).
13

48.4 (NCH2), 112.0 (C6), 117.1 (=CH2), 122.1 (C4), 124.5 (C6),
125.4 (C2), 127.4 (C5), 128.2 (C2), 128.3 (C4), 128.7 (C5), 129.6
(C3), 135.2 (=CH), 138.4 (C3), 139.0 (C1), 144.8 (C1).
MS (EI, 70 eV): m/z (%) = 271 (35Cl, 29) [M+], 243 (1), 230 (1), 180
(9), 166 (35), 151 (3), 105 (100), 79 (12).
2-Allyl-4-methyl-N-(4-methylbenzyl)aniline (2h)
1
H NMR (400 MHz, CDCl3): d = 2.33 (s, 3 H, 4-CH3), 2.42 (s, 3 H,

4-CH3), 3.37 (d, J = 6.0 Hz, 2 H, CH2CH=), 4.36 (s, 2 H, NCH2),
5.15 (dq, J = 17.2, 1.6 Hz, 1 H, =CHAHB), 5.19 (dq, J = 10.0, 1.2
Hz, 1 H, =CHAHB), 6.03 (ddt, J = 17.2, 10.0, 6.0 Hz, 1 H, =CH),
6.65 (d, J = 8.0 Hz, 1 H, H6), 6.97 (d, J = 1.6 Hz, 1 H, H3), 7.02 (dd,
J = 8.4, 1.6 Hz, 1 H, H5), 7.22 (d, J = 8.0 Hz, 2 H, H3, H5), 7.32
(d, J = 8.0 Hz, 2 H, H2, H6).
13
C NMR (100 MHz, CDCl3): d = 20.5 (4-CH3), 21.2 (4-CH3), 36.6
(CH2CH=), 48.4 (NCH2), 111.2 (C6), 116.3 (=CH2), 123.9 (C2),
126.7 (C4), 127.6 (C2, C6), 128.1 (C5), 129.4 (C3, C5), 130.7
(C3), 136.3 (=CH), 136.6 (C1), 136.8 (C4), 144.0 (C1).
MS (EI, 70 eV): m/z (%) = 251 (56) [M+], 222 (9), 160 (7), 146 (72),
132 (17), 131 (23), 105 (100), 91 (8).
2-Allyl-4-methyl-N-(3-methylbenzyl)aniline (2i)
1
H NMR (400 MHz, CDCl3): d = 2.29 (s, 3 H, 4-CH3), 2.38 (s, 3 H,

3-CH3), 3.34 (d, J = 6.2 Hz, 2 H, CH2CH=), 4.32 (s, 2 H, NCH2),
5.11 (dq, J = 17.4, 1.7 Hz, 1 H, =CHAHB), 5.15 (dq, J = 10.2, 1.7
Hz, 1 H, =CHAHB), 5.99 (ddt, J = 17.4, 10.2, 6.2 Hz, 1 H, =CH),
6.62 (d, J = 8.1 Hz, 1 H, H6), 6.94 (d, J = 1.7 Hz, 1 H, H3), 6.98 (dd,
J = 8.1, 1.7 Hz, 1 H, H5), 7.12 (d, J = 7.3 Hz, 1 H, H4), 7.19 (d,
J = 7.6 Hz, 1 H, H6), 7.23 (d, J = 1.6 Hz, 1 H, H2), 7.26 (t, J = 7.5
Hz, 1 H, H5).
13
C NMR (100 MHz, CDCl3): d = 20.6 (4-CH3), 21.7 (3-CH3), 36.7

(CH2CH=), 49.1 (NCH2), 112.2 (C6), 117.0 (=CH2), 124.9 (C2),
125.4 (C6), 126.9 (C4), 128.8 (C5), 128.9 (C2), 129.2 (C4), 129.4
(C5), 131.5 (C3), 137.1 (=CH), 137.1 (C3), 139.1 (C1), 143.9
(C1).
MS (EI, 70 eV): m/z (%) = 251(56) [M+], 222 (10), 160 (13), 146
(100), 132 (23), 131 (44), 105 (71), 79 (15).
11-Ethyl-6,11-dihydrodibenz[b,e]azepines 3; General Procedure
Method A: A suspension of 2-allyl-N-benzylaniline 2 (1.0 g) in 95%
H2SO4 (2 mL) was stirred at 6090 C for 560 min (TLC control).
The mixture was cooled to r.t. and then it was poured into ice H2O
(50 mL), treated with 25% NH4OH soln to pH 8, and extracted with
CH2Cl2 (3 50 mL). The combined organic extracts were dried (anhyd Na2SO4), filtered, and evaporated to dryness in vacuo. The
crude material was purified by column chromatography (silica gel,
heptaneEtOAc, 20:1, 15:1, and 10:1). Compounds 3ac,ei were
obtained as viscous maroon oils, and compound 3d as white crystals.
Method B: A suspension of 2-allyl-N-benzylaniline 2 (1.0 g) in 70%
HClO4 (4 mL) was stirred at 85120 C for 3060 min (TLC control). The mixture was cooled to r.t. and then it was poured into ice
H2O (50 mL), treated with sat. Na2CO3 soln to pH 8, and extracted
with CH2Cl2 (3 50 mL). The combined organic extracts were

dried (anhyd Na2SO4), filtered, and evaporated to dryness in vacuo.
The crude material was purified by column chromatography (silica
gel, heptaneEtOAc, 20:1, 15:1, and 10:1).
11-Ethyl-6,11-dihydro-5H-dibenz[b,e]azepine (3a)
IR (KBr): 3416 (NH), 2963 (CH Ar), 1598 (NH), 1497 cm1
(C=C Ar).
1
H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.4 Hz, 3 H, 13-CH3),
2.152.25 (m, 2 H, 12-CH2), 3.45 (br s, 1 H, NH), 3.69 (t, J = 7.3
Hz, 1 H, H11), 4.00 (d, J = 14.8 Hz, 1 H, H6A), 4.95 (d, J = 14.8 Hz,
1 H, H6B), 6.53 (d, J = 8.0 Hz, 1 H, H4), 6.72 (td, J = 8.0, 1.0 Hz, 1
H, H2), 7.01 (td, J = 8.0, 1.0 Hz, 1 H, H3), 7.10 (dd, J = 8.0, 1.0 Hz,
1 H, H1), 7.15 (dd, J = 8.0, 2.0 Hz, 1 H, H7), 7.207.24 (m, 2 H, H8,
H9), 7.26 (dd, J = 8.0, 2.0 Hz, 1 H, H10).
13
C NMR (100 MHz, CDCl3): d = 13.0 (13-CH3), 31.6 (12-CH2),
51.1 (C6), 54.8 (C11), 117.9 (C4), 118.2 (C2), 126.8 (C10), 127.2
(C3), 127.4 (C9), 128.3 (C8), 129.0 (C7), 130.2 (C11a), 130.8 (C1),
136.5 (C6a), 142.1 (C10a), 146.2 (C4a).
MS (EI, 70 eV): m/z (%): 223 (14) [M+], 194 (100), 178 (8), 165
(11), 116 (10), 96 (10).
Anal. Calcd for C16H17N: C, 86.05; H, 7.67; N, 6.27. Found: C,
86.13; H, 7.81; N, 6.05.
11-Ethyl-2-fluoro-6,11-dihydro-5H-dibenz[b,e]azepine (3b)
(C=C Ar).
1
2.042.26 (m, 2 H, 12-CH2), 3.44 (br s, 1 H, NH), 3.71 (t, J = 7.6
Hz, 1 H, H11), 4.20 (d, J = 14.6 Hz, 1 H, H6A), 4.72 (d, J = 14.6 Hz,
1 H, H6B), 6.49 (dd, J = 8.0, 5.0 Hz, 1 H, H4), 6.72 (dd, J = 8.0, 3.0
Hz, 1 H, H3), 6.82 (dd, J = 10.0, 3.0 Hz, 1 H, H1), 7.14 (dd, J = 8.0,
2.0 Hz, 1 H, H7), 7.20 (dd, J = 8.0, 2.0 Hz, 1 H, H10), 7.227.25 (m,
2 H, H8, H9).
13

49.7 (C6), 53.1 (C11), 113.7 (d, 2JC,F = 20.0 Hz, C3), 116.7 (d,
2
JC,F = 20.0 Hz, C1), 119.5 (d, 3JC,F = 10.0 Hz, C4), 126.8 (C8),
127.4 (C9), 128.2 (C7), 129.1 (C10), 130.0 (C11a), 136.5 (C6a),
141.3 (C10a), 142.5 (C4a), 156.4 (d, 1JC,F = 230.0 Hz, C2).
MS (EI, 70 eV): m/z (%) = 241 (17) [M+], 212 (100), 196 (15), 183
(17), 165 (10), 116 (9).
Anal. Calcd for C16H16FN: C, 79.64; H, 6.68; N, 5.80. Found: C,
79.70; H, 6.80; N, 5.65.
2-Chloro-11-ethyl-6,11-dihydro-5H-dibenz[b,e]azepine (3c)
(C=C Ar).
1
2.152.23 (m, 2 H, 12-CH2), 3.63 (t, J = 7.3 Hz, 1 H, H11), 3.91 (br
s, 1 H, NH), 4.17 (d, J = 14.4 Hz, 1 H, H6A), 4.77 (d, J = 14.4 Hz, 1
H, H6B), 6.40 (d, J = 8.5 Hz, 1 H, H4), 6.91 (dd, J = 8.5, 2.3 Hz, 1
H, H3), 7.10 (d, J = 2.3 Hz, 1 H, H1), 7.13 (dd, J = 8.0, 2.0 Hz, 1 H,
H7), 7.17 (dd, J = 8.0, 2.0 Hz, 1 H, H10), 7.21 (td, J = 8.0, 2.0 Hz,
1 H, H8), 7.23 (td, J = 8.0, 2.0 Hz, 1 H, H9).
13
51.1 (C6), 54.8 (C11), 117.9 (C4), 118.2 (C2), 126.8 (C10), 127.2
(C3), 127.4 (C9), 128.3 (C8), 129.0 (C7), 130.2 (C11a), 130.8 (C1),
136.5 (C6a), 142.1 (C10a), 146.2 (C4a).
MS (EI, 70 eV): m/z (%) = 257 (35Cl, 19) [M+], 228 (100), 193 (46),
165 (17), 115 (6), 89 (5).
Anal. Calcd for C16H16ClN: C, 74.55; H, 6.26; N, 5.43. Found: C,
74.38; H, 6.49; N, 5.35.
PAPER
11-Ethyl-2-methyl-6,11-dihydro-5H-dibenz[b,e]azepine (3d)
White crystals; mp 6970 C (heptane).
(C=C Ar).
1
2.192.29 (m, 2 H, 12-CH2), 2.31 (s, 3 H, 2-CH3), 3.80 (t, J = 6.9
Hz, 1 H, H11), 3.95 (br s, 1 H, NH), 4.16 (d, J = 14.2 Hz, 1 H, H6A),
4.83 (d, J = 14.2 Hz, 1 H, H6B), 6.52 (d, J = 8.0 Hz, 1 H, H4), 6.88
(dd, J = 8.0, 1.6 Hz, 1 H, H3), 6.97 (d, J = 1.6 Hz, 1 H, H1), 7.16
(dd, J = 7.2, 2.0 Hz, 1 H, H7), 7.217.26 (m, 3 H, H8, H9, H10).
13

31.7 (12-CH2), 49.7 (C6), 54.5 (C11), 118.5 (C4), 126.7 (C8), 127.3
(C9), 127.9 (C11a), 128.0 (C3), 128.2 (C2), 128.3 (C10), 129.5
(C7), 131.8 (C1), 136.9 (C6a), 142.1 (C10a), 143.9 (C4a).
MS (EI, 70 eV): m/z (%) = 237 (23) [M+], 208 (100), 193 (22), 178
(4), 165 (6), 96 (5).
86.14; H, 8.00; N, 5.85.
11-Ethyl-2-methoxy-6,11-dihydro-5H-dibenz[b,e]azepine (3e)
(C=C Ar).
1
2.102.33 (m, 2 H, 12-CH2), 3.78 (s, 3 H, 2-OCH3), 3.83 (t, J = 6.5
4.71 (d, J = 14.7 Hz, 1 H, H6B), 6.58 (d, J = 8.5 Hz, 1 H, H4), 6.65
(dd, J = 8.5, 2.8 Hz, 1 H, H3), 6.72 (d, J = 2.8 Hz, 1 H, H1), 7.11
(dd, J = 7.4, 2.0 Hz, 1 H, H7), 7.177.24 (m, 3 H, H8, H9, H10).
13
50.4 (C6), 55.7 (C11), 55.7 (2-OCH3), 112.9 (C3), 116.5 (C1),
119.9 (C4), 126.7 (C9), 127.1 (C8), 128.4 (C7, C10), 131.1 (C11a),
137.0 (C6a), 140.4 (C4a), 141.6 (C10a), 153.2 (C2).

2.112.19 (m, 2 H, 12-CH2), 2.34 (s, 3 H, 8-CH3), 3.42 (br s, 1 H,
NH), 3.74 (t, J = 7.6 Hz, 1 H, H11), 3.91 (d, J = 14.8 Hz, 1 H, H6A),
5.03 (d, J = 14.8 Hz, 1 H, H6B), 6.41 (dd, J = 8.4, 1.3 Hz, 1 H, H4),
6.93 (d, J = 8.4 Hz, 1 H, H3), 6.97 (s, 1 H, H7), 7.067.12 (m, 3 H,
H1, H9, H10).
13
32.7 (12-CH2), 49.1 (C6), 53.1 (C11), 119.2 (C4), 122.5 (C2), 127.0
(C3, C7), 128.3 (C9), 129.1 (C11a), 129.2 (C10), 130.5 (C1), 136.0
(C8), 136.6 (C6a), 138.6 (C10a), 144.8 (C4a).
MS (EI, 70 eV): m/z (%) = 271 (35Cl, 23) [M+], 242 (100), 240 (4),
213 (1), 181 (1), 179 (2).
75.23; H, 6.80; N, 5.09.
11-Ethyl-2,9-dimethyl-6,11-dihydro-5H-dibenz[b,e]azepine
(3h)
(C=C Ar).
1
2.172.27 (m, 2 H, 12-CH2), 2.29 (s, 3 H, 2-CH3), 2.38 (s, 3 H, 9CH3), 3.75 (t, J = 7.4 Hz, 1 H, H11), 3.95 (br s, 1 H, NH), 4.14 (d,
J = 14.0 Hz, 1 H, H6A), 4.80 (d, J = 14.0 Hz, 1 H, H6B), 6.50 (d,
J = 8.0 Hz, 1 H, H4), 6.86 (dd, J = 8.0, 1.6 Hz, 1 H, H3), 6.94 (d,
J = 1.6 Hz, 1 H, H1), 7.05 (br s, 3 H, H7, H8, H10).
13

21.2 (9-CH3), 31.5 (12-CH2), 49.3 (C6), 54.3 (C11), 118.5 (C4),
127.3 (C8), 127.7 (C11a), 128.0 (C3), 128.2 (C2), 128.3 (C10),
130.1 (C7), 131.7 (C1), 133.8 (C6a), 136.8 (C9), 142.1 (C10a),
143.8 (C4a).
MS (EI, 70 eV): m/z (%) = 251 (21) [M+], 222 (100), 207 (23), 191
(4), 178 (4), 165 (3), 103 (7).
MS (EI, 70 eV): m/z (%): 253 (32) [M+], 224 (100), 209 (7), 193 (9),
180 (25), 152 (7).

86.13; H, 8.38; N, 5.49.
Anal. Calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found: C,

80.48; H, 7.44; N, 5.60.
11-Ethyl-2,8-dimethyl-6,11-dihydro-5H-dibenz[b,e]azepine (3i)
(C=C Ar).
11-Ethyl-9-methyl-6,11-dihydro-5H-dibenz[b,e]azepine (3f)
(C=C Ar).
1
2.142.23 (m, 2 H, 12-CH2), 2.34 (s, 3 H, 9-CH3), 3.75 (t, J = 7.1
4.81 (d, J = 14.0 Hz, 1 H, H6B), 6.51 (dd, J = 8.0, 1.0 Hz, 1 H, H4),
6.70 (td, J = 8.0, 1.0 Hz, 1 H, H2), 6.99 (td, J = 8.0, 1.0 Hz, 1 H,
H3), 7.017.06 (m, 3 H, H7, H8, H10), 7.08 (dd, J = 8.0, 1.0 Hz, 1
H, H1).
13
29.8 (12-CH2), 49.0 (C6), 54.3 (C11), 118.1 (C4), 118.3 (C2), 127.4
(C3, C10), 127.5 (C11a), 128.3 (C7), 130.0 (C8), 131.3 (C1), 133.7
(C6a), 137.1 (C9), 142.2 (C10a), 146.3 (C4a).
1
2.112.25 (m, 2 H, 12-CH2), 2.27 (s, 3 H, 2-CH3), 2.35 (s, 3 H, 8CH3), 3.84 (t, J = 6.8 Hz, 1 H, H11), 3.85 (br s, 1 H, NH), 4.10 (d,
J = 14.4 Hz, 1 H, H6A), 4.79 (d, J = 14.4 Hz, 1 H, H6B), 6.49 (d,
J = 8.0 Hz, 1 H, H4), 6.84 (dd, J = 8.0, 1.7 Hz, 1 H, H3), 6.92 (d,
J = 1.7 Hz, 1 H, H1), 6.93 (s, 1 H, H7), 7.04 (dd, J = 7.6, 1.1 Hz, 1
H, H9), 7.10 (d, J = 7.6 Hz, 1 H, H10).
13
21.0 (8-CH3), 32.0 (12-CH2), 49.7 (C6), 54.0 (C11), 118.5 (C4),
127.8 (C2), 127.9 (C3), 128.5 (C11a), 129.5 (C7), 129.6 (C9, C10),
131.7 (C1), 136.2 (C8), 136.7 (C6a), 139.1 (C10a), 143.9 (C4a).
MS (EI, 70 eV): m/z (%) = 251 (20) [M+], 222 (100), 207 (29), 191
(5), 178 (4), 165 (4), 103 (6).
MS (EI, 70 eV): m/z (%): 237 (18) [M+], 208 (100), 193 (24), 178
(4), 165 (6), 96 (7).

85.88; H, 8.53; N, 5.50.

86.14; H, 8.00; N, 5.85.
11-Ethyldibenz[b,e]azepines 4; General Procedure

PCC (1 mmol) was added portionwise within 10 min to a stirred and
cooled (ice bath) soln of dihydrodibenz[b,e]azepine 3 (1 mmol) in
CH2Cl2 (10 mL). Upon complete addition, the suspension was
stirred at 0 C for an additional 2030 min (TLC control). The resulting orange precipitate was removed by filtration and the filtrate
was concentrated in vacuo. The crude material was purified by column chromatography (silica gel, heptaneEtOAc, 10:1, 5:1). Compounds 4ai were obtained as high-viscosity yellow oils.
2-Chloro-11-ethyl-8-methyl-6,11-dihydro-5Hdibenz[b,e]azepine (3g)
(C=C Ar).
PAPER
A. Palma et al.
11-Ethyl-11H-dibenz[b,e]azepine (4a)
Time: 35 min; yield: 95%.
IR (KBr): 3018 (CH Ar), 1617 (C=N), 1482 (C=C Ar), 1299 cm1
(CN).
(CN).
1
1.611.75 (m, 2 H, 12-CH2), 3.69 (t, J = 8.0 Hz, 1 H, H11), 7.20 (dd,
J = 7.6, 1.5 Hz, 1 H, H10), 7.21 (td, J = 8.0, 1.8 Hz, 1 H, H3), 7.26
(dd, J = 8.0, 1.2 Hz, 1 H, H4), 7.29 (dd, J = 8.0, 1.8 Hz, 1 H, H1),
7.34 (td, J = 7.6, 1.0 Hz, 1 H, H8), 7.46 (td, J = 7.6, 1.2 Hz, 1 H,
H9), 7.47 (td, J = 8.0, 1.2 Hz, 1 H, H2), 7.53 (d, J = 7.6 Hz, 1 H,
H7), 8.79 (s, 1 H, H6).
13
54.3 (C11), 126.7 (C3), 127.2 (C4), 128.3 (C8), 128.4 (C2), 129.0
(C1), 129.6 (C10), 129.9 (C7), 130.1 (C6a), 131.2 (C9), 135.5
(C11a), 143.9 (C4a), 144.9 (C10a), 159.6 (C6).
MS (EI, 70 eV): m/z (%) = 221 (12) [M+], 192 (100), 165 (19), 139
(3), 89 (2), 63 (5), 51 (3).
86.70; H, 6.98; N, 6.29.

1.621.72 (m, 2 H, 12-CH2), 2.36 (s, 3 H, 2-CH3), 3.64 (t, J = 8.0
Hz, 1 H, H11), 7.03 (s, 1 H, H1), 7.11 (dd, J = 8.0, 1.2 Hz, 1 H, H3),
7.27 (d, J = 8.4 Hz, 1 H, H10), 7.31 (td, J = 7.6, 1.0 Hz, 1 H, H8),
7.39 (d, J = 8.0 Hz, 1 H, H4), 7.44 (td, J = 7.6, 1.2 Hz, 1 H, H9),
7.51 (d, J = 7.6 Hz, 1 H, H7), 8.74 (s, 1 H, H6).
13
24.4 (12-CH2), 54.9 (C11), 126.6 (C8), 128.1 (C3), 128.9 (C4),
129.0 (C10), 130.1 (C7), 130.5 (C1), 131.3 (C6a), 131.7 (C9), 135.9
(C11a), 137.9 (C2), 142.1 (C4a), 145.2 (C10a), 159.4 (C6).
MS (EI, 70 eV): m/z (%) = 235 (14) [M+], 206 (100), 191 (10), 190
(13), 178 (8).
86.80; H, 7.25; N, 5.92.
11-Ethyl-2-methoxy-11H-dibenz[b,e]azepine (4e)
(CN).
11-Ethyl-2-fluoro-11H-dibenz[b,e]azepine (4b)
IR (KBr): 2964 (CH Ar), 1618 (C=N), 1481 (C=C Ar), 1243 cm
(CN).
1
1.591.74 (m, 2 H, 12-CH2), 3.61 (t, J = 8.0 Hz, 1 H, H11), 6.90 (dd,
J = 9.2, 3.0 Hz, 1 H, H1), 6.98 (td, J = 8.0, 3.0 Hz, 1 H, H3), 7.25
(d, J = 7.2 Hz, 1 H, H10), 7.36 (td, J = 7.6, 1.2 Hz, 1 H, H8), 7.43
(t, J = 9.2 Hz, 1 H, H4), 7.46 (td, J = 7.6, 1.2 Hz, 1 H, H9), 7.52 (d,
J = 7.6 Hz, 1 H, H7), 8.73 (s, 1 H, H6).
13

54.7 (C11), 114.1 (d, 2JC,F = 20.0 Hz, C3), 115.8 (d, 2JC,F = 20.0 Hz,
C1), 127.0 (C8), 128.9 (C10), 130.5 (C7), 130.6 (C6a), 130.9 (d,
3
JC,F = 10.0 Hz, C4), 131.9 (C9), 137.0 (d, 3JC,F = 10.0 Hz, C11a),
141.1 (d, 4JC,F = 10.0 Hz, C4a), 144.4 (C10a), 159.6 (C6), 162.5 (d,
1
JC,F = 250.0 Hz, C2).

1.611.71 (m, 2 H, 12-CH2), 3.62 (t, J = 8.0 Hz, 1 H, H11), 3.81 (s,
3 H, 2-OCH3), 6.74 (d, J = 2.8 Hz, 1 H, H1), 6.85 (dd, J = 8.7, 2.8
Hz, 1 H, H3), 7.25 (d, J = 7.6 Hz, 1 H, H10), 7.33 (td, J = 7.4, 1.0
Hz, 1 H, H8), 7.44 (d, J = 8.7 Hz, 1 H, H4), 7.44 (td, J = 7.4, 1.2 Hz,
1 H, H9), 7.51 (d, J = 7.6 Hz, 1 H, H7), 8.67 (s, 1 H, H6).
13
55.1 (C11), 55.5 (2-OCH3), 112.4 (C3), 114.6 (C1), 126.7 (C8),
128.9 (C10), 130.5 (C4), 130.6 (C7), 130.7 (C6a), 131.6 (C9), 137.3
(C11a), 138.4 (C4a), 144.4 (C10a), 158.1 (C6), 159.6 (C2).
MS (EI, 70 eV): m/z (%) = 251 (21) [M+], 222 (100), 207 (3), 190
(4), 179 (20), 178 (10).
Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C,
81.07; H, 6.95; N, 5.48.
MS (EI, 70 eV): m/z (%) = 239 (12) [M+], 210 (100), 190 (12), 183
(16), 157 (3), 133 (2), 63 (8), 51 (2).
11-Ethyl-9-methyl-11H-dibenz[b,e]azepine (4f)
Anal. Calcd for C16H14FN: C, 80.31; H, 5.90; N, 5.85. Found: C,

8.14; H, 6.03; N, 5.79.
(CN).
2-Chloro-11-ethyl-11H-dibenz[b,e]azepine (4c)
(CN).
1
1.591.73 (m, 2 H, 12-CH2), 3.61 (t, J = 8.0 Hz, 1 H, H11), 7.20 (d,
J = 2.4 Hz, 1 H, H1), 7.24 (dd, J = 8.4, 2.4 Hz, 1 H, H3), 7.26 (d,
J = 7.6 Hz, 1 H, H10), 7.35 (td, J = 7.6, 1.0 Hz, 1 H, H8), 7.39 (d,
J = 8.4 Hz, 1 H, H4), 7.46 (td, J = 7.6, 1.2 Hz, 1 H, H9), 7.52 (d,
J = 7.6 Hz, 1 H, H7), 8.75 (s, 1 H, H6).
13

54.6 (C11), 127.0 (C8), 127.3 (C3), 128.9 (C10), 129.2 (C1), 130.3
(C4), 130.6 (C6a, C7), 132.0 (C9), 133.3 (C2), 137.5 (C11a), 143.2
(C4a), 144.7 (C10a), 160.5 (C6).
1
1.601.74 (m, 2 H, 12-CH2), 2.39 (s, 3 H, 9-CH3), 3.65 (t, J = 8.0
Hz, 1 H, H11), 7.11 (s, 1 H, H10), 7.14 (d, J = 7.7 Hz, 1 H, H8), 7.20
(dd, J = 7.7, 1.7 Hz, 1 H, H1), 7.24 (td, J = 7.7, 1.4 Hz, 1 H, H2),
7.30 (td, J = 7.7, 1.7 Hz, 1 H, H3), 7.41 (d, J = 7.7 Hz, 1 H, H7),
7.51 (d, J = 7.7 Hz, 1 H, H4), 8.76 (s, 1 H, H6).
13

24.4 (12-CH2), 54.9 (C11), 127.2 (C2), 127.4 (C3), 127.6 (C8),
128.2 (C6a), 128.9 (C4), 129.4 (C10), 129.5 (C1), 130.1 (C7), 136.0
(C11a), 142.5 (C9), 144.5 (C4a), 145.4 (C10a), 160.0 (C6).
MS (EI, 70 eV): m/z (%) = 235 (11) [M+], 206 (100), 191 (10), 190
(13), 178 (6).
86.70; H, 7.38; N, 5.89.
MS (EI, 70 eV): m/z (%) = 255 (35Cl, 12) [M+], 226 (100), 199 (4),
190 (34), 163 (11), 63 (5), 51 (2).
2-Chloro-11-ethyl-8-methyl-11H-dibenz[b,e]azepine (4g)

74.98; H, 5.45; N, 5.54.
(CN).
11-Ethyl-2-methyl-11H-dibenz[b,e]azepine (4d)
1
1.571.72 (m, 2 H, 12-CH2), 2.36 (s, 3 H, 8-CH3), 3.58 (t, J = 8.0
PAPER
Hz, 1 H, H11), 7.14 (d, J = 8.0 Hz, 1 H, H10), 7.19 (d, J = 2.0 Hz,
1 H, H1), 7.24 (dd, J = 8.4, 2.0 Hz, 1 H, H3), 7.27 (d, J = 8.0 Hz, 1
H, H9), 7.32 (br s, 1 H, H7), 7.38 (d, J = 8.4 Hz, 1 H, H4), 8.71 (s,
1 H, H6).
13

24.3 (12-CH2), 54.1 (C11), 127.2 (C3), 128.9 (C1), 129.1 (C10),
130.3 (C7), 130.4 (C6a), 131.1 (C4), 132.9 (C9), 133.2 (C2), 136.7
(C8), 137.7 (C11a), 142.0 (C10a), 143.2 (C4a), 160.6 (C6).
MS (EI, 70 eV): m/z (%) = 269 (35Cl, 15) [M+], 240 (100), 204 (10),
190 (15), 178 (5), 77 (3), 65 (2).
75.60; H, 6.04; N, 5.09.
11-Ethyl-2,9-dimethyl-11H-dibenz[b,e]azepine (4h)
(CN).
1
1.611.71 (m, 2 H, 12-CH2), 2.36 (s, 3 H, 2-CH3), 2.39 (s, 3 H, 9CH3), 3.59 (t, J = 8.0 Hz, 1 H, H11), 7.02 (s, 1 H, H1), 7.06 (s, 1 H,
H10), 7.11 (dd, J = 8.0, 1.2 Hz, 1 H, H3), 7.13 (d, J = 8.0 Hz, 1 H,
H8), 7.39 (d, J = 8.0 Hz, 1 H, H4), 7.41 (d, J = 8.0 Hz, 1 H, H7),
8.71 (s, 1 H, H6).
material was purified by column chromatography (silica gel, heptaneEtOAc, 10:1, 5:1, and 2:1).
9-Ethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)one (5a)
Time: 24 h; pale-yellow crystals; yield: 55%; mp 128129 C (heptane).
IR (KBr): 2962 (CH Ar), 1695 (C=O), 1478 (C=C Ar), 1360 cm1
(CN).
1

2.242.40 (m, 2 H, 14-CH2), 3.64 (d, J = 15.2 Hz, 1 H, H2A), 3.99
(dd, J = 15.2, 2.0 Hz, 1 H, H2B), 4.40 (t, J = 7.6 Hz, 1 H, H9), 6.23
(d, J = 0.8 Hz, 1 H, H13b), 7.08 (dd, J = 8.0, 1.0 Hz, 1 H, H5), 7.14
(td, J = 8.0, 1.0 Hz, 1 H, H7), 7.23 (dd, J = 8.0, 1.0 Hz, 1 H, H8),
7.247.30 (m, 3 H, H6, H12, H13), 7.327.36 (m, 2 H, H10, H11).
13
33.6 (C2), 42.1 (C9), 64.6 (C13b), 124.5 (C5), 124.8 (C6, C10),
126.8 (C12), 127.1 (C7), 128.1 (C8), 128.5 (C13), 128.6 (C8a),
128.8 (C11), 135.4 (C13a), 141.3 (C9a), 143.5 (C4a), 171.7 (C3).
MS (EI, 70 eV): m/z (%) = 295 (57) [M+], 266 (72), 248 (12), 221
(14), 220 (26), 206 (21), 192 (100).
Anal. Calcd for C18H17NOS: C, 73.19; H, 5.80; N, 4.74. Found: C,
73.00; H, 5.95; N, 4.84.
13

21.5 (9-CH3), 24.4 (12-CH2), 55.0 (C11), 127.4 (C8), 128.0 (C3),
128.3 (C6a), 128.9 (C10), 129.4 (C4), 130.1 (C1), 130.6 (C7), 135.8
(C11a), 137.6 (C2), 142.3 (C4a, C9), 145.2 (C10a), 159.3 (C6).
9-Ethyl-7-fluoro-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5b)
Time: 28 h; yellow crystals; yield: 60%; mp 131132 C (heptane).
MS (EI, 70 eV): m/z (%) = 249 (12) [M+], 220 (100), 205 (4), 204
(8), 190 (14), 178 (5).
(CN).

86.81; H, 7.59; N, 5.68.
11-Ethyl-2,8-dimethyl-11H-dibenz[b,e]azepine (4i)
(CN).
1

1.611.70 (m, 2 H, 12-CH2), 2.35 (s, 3 H, 2-CH3), 2.36 (s, 3 H, 8CH3), 3.61 (t, J = 8.0 Hz, 1 H, H11), 7.01 (d, J = 1.3 Hz, 1 H, H1),
7.10 (dd, J = 8.0, 1.3 Hz, 1 H, H3), 7.16 (d, J = 7.7 Hz, 1 H, H10),
7.26 (dd, J = 7.7, 1.0 Hz, 1 H, H9), 7.32 (s, 1 H, H7), 7.38 (d, J = 8.0
Hz, 1 H, H4), 8.70 (s, 1 H, H6).
13

21.0 (8-CH3), 24.6 (12-CH2), 54.5 (C11), 128.0 (C3), 128.9 (C4,
C10), 130.1 (C1), 130.5 (C6a), 131.0 (C7), 132.6 (C9), 136.1
(C11a), 136.3 (C8), 137.8 (C2), 142.1 (C4a), 142.5 (C10a), 159.6
(C6).
1
2.162.36 (m, 2 H, 14-CH2), 3.63 (d, J = 15.6 Hz, 1 H, H2A), 3.98
(dd, J = 15.6, 2.0 Hz, 1 H, H2B), 4.36 (t, J = 7.6 Hz, 1 H, H9), 6.19
(d, J = 1.2 Hz, 1 H, H13b), 6.946.98 (m, 2 H, H6, H8), 7.09 (dd,
J = 7.6, 1.2 Hz, 1 H, H13), 7.16 (td, J = 7.6, 1.2 Hz, 1 H, H12), 7.26
(td, J = 7.6, 1.2 Hz, 1 H, H11), 7.287.30 (m, 1 H, H5), 7.32 (d,
J = 7.6 Hz, 1 H, H10).
13
33.5 (C2), 42.2 (C9), 64.5 (C13b), 112.0 (d, 2JC,F = 30.0 Hz, C8),
114.0 (d, 2JC,F = 30.0 Hz, C6), 124.6 (C10), 127.1 (C12), 128.7
(C13), 128.9 (C11), 129.8 (d, 3JC,F = 10.0 Hz, C5), 131.0 (C8a),
134.3 (C13a), 140.6 (C9a), 146.1 (d, 4JC,F = 10.0 Hz, C4a), 162.4 (d,
1
JC,F = 240.0 Hz, C7), 171.8 (C3).
MS (EI, 70 eV): m/z (%) = 313 (45) [M+], 284 (46), 266 (10), 239
(16), 238 (23), 224 (21), 210 (100).
Anal. Calcd for C18H16FNOS: C, 68.99; H, 5.15; N, 4.47. Found: C,
68.90; H, 5.03; N, 4.60.
MS (EI, 70 eV): m/z (%) = 249 (12) [M+], 220 (100), 204 (8), 190
(14), 178 (5), 164 (1).
7-Chloro-9-ethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5c)

86.90; H, 7.49; N, 5.53.
(CN).
Dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-ones 5; General Procedure

A mixture of morphanthridine 4 (1 mmol), mercaptoacetic acid (3
mmol) and a catalytic amount of BF3OEt2 (1 drop) in anhyd toluene
(50 mL) was refluxed for 2440 h using a DeanStark trap. The
mixture was cooled to r.t. and then it was poured into H2O (50 mL),
neutralized with sat. NaHCO3 soln, and extracted with CH2Cl2
(3 50 mL). The combined organic extracts were dried (anhyd
Na2SO4), filtered, and evaporated to dryness in vacuo. The crude
1
2.172.37 (m, 2 H, 14-CH2), 3.63 (d, J = 15.6 Hz, 1 H, H2A), 3.98
(dd, J = 15.6, 2.0 Hz, 1 H, H2B), 4.36 (t, J = 7.6 Hz, 1 H, H9), 6.20
(s, 1 H, H13b), 7.09 (d, J = 8.0 Hz, 1 H, H13), 7.16 (t, J = 8.0 Hz, 1
H, H12), 7.237.30 (m, 4 H, H5, H6, H8, H11), 7.32 (d, J = 8.0 Hz,
1 H, H10).
13
33.6 (C2), 42.2 (C9), 64.5 (C13b), 125.0 (C5), 125.1 (C10), 127.1
(C6), 127.3 (C12), 128.7 (C8), 129.0 (C13), 129.4 (C11), 133.8
PAPER
A. Palma et al.
(C8a), 134.1 (C13a), 134.4 (C7), 140.5 (C9a), 145.4 (C4a), 171.7
(C3).
6.98 (d, J = 7.8 Hz, 1 H, H13), 7.14 (s, 1 H, H10), 7.267.34 (m, 4
H, H5, H6, H7, H8).
MS (EI, 70 eV): m/z (%) = 329 (35Cl, 47) [M+], 300 (51), 282 (12),
255 (15), 254 (17), 240 (18), 226 (100).
13
Anal. Calcd for C18H16ClNOS: C, 65.54; H, 4.89; N, 4.25. Found:

C, 65.70; H, 4.73; N, 4.18.
9-Ethyl-7-methyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5d)
(CN).
1
2.28 (s, 3 H, 7-CH3), 2.222.38 (m, 2 H, 14-CH2), 3.63 (dd,
J = 15.4, 0.7 Hz, 1 H, H2A), 3.98 (dd, J = 15.4, 1.9 Hz, 1 H, H2B),
4.36 (t, J = 7.6 Hz, 1 H, H9), 6.21 (s, 1 H, H13b), 7.07 (br s, 1 H,
H8), 7.08 (d, J = 7.8 Hz, 2 H, H5, H13), 7.14 (td, J = 7.6, 1.0 Hz, 1
H, H12), 7.22 (d, J = 7.8 Hz, 1 H, H6), 7.25 (td, J = 7.3, 1.7 Hz, 1
H, H11), 7.33 (d, J = 7.8 Hz, 1 H, H10).
13
21.6 (7-CH3), 33.6 (C2), 42.0 (C9), 64.6 (C13b), 124.8 (C10), 125.2
(C8), 126.7 (C12), 127.7 (C11), 127.8 (C6), 128.1 (C5), 128.7
(C13), 132.7 (C8a), 134.6 (C13a), 138.5 (C7), 141.4 (C9a), 143.2
(C4a), 171.7 (C3).
+
MS (EI, 70 eV): m/z (%) = 309 (43) [M ], 280 (61), 262 (7), 235
(11), 234 (17), 220 (10), 206 (100).
73.87; H, 6.12; N, 4.61.
9-Ethyl-7-methoxy-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5e)
(CN).
1

2.202.33 (m, 2 H, 14-CH2), 3.63 (d, J = 15.5 Hz, 1 H, H2A), 3.77
(s, 3 H, 7-OCH3), 3.97 (dd, J = 15.5, 2.0 Hz, 1 H, H2B), 4.33 (t,
J = 7.6 Hz, 1 H, H9), 6.18 (d, J = 0.7 Hz, 1 H, H13b), 6.77 (dd,
J = 8.7, 2.8 Hz, 1 H, H6), 6.79 (d, J = 2.8 Hz, 1 H, H8), 7.07 (dd,
J = 7.6, 1.0 Hz, 1 H, H13), 7.13 (td, J = 7.6, 1.0 Hz, 1 H, H12), 7.28
(d, J = 8.7 Hz, 1 H, H5), 7.28 (td, J = 7.6, 1.0 Hz, 1 H, H11), 7.32
(d, J = 7.6 Hz, 1 H, H10).
13
33.6 (C2), 42.2 (C9), 55.5 (7-OCH3), 64.7 (C13b), 111.1 (C6),
111.4 (C8), 124.9 (C10), 126.8 (C12), 128.0 (C8a), 128.6 (C5),
128.8 (C13), 128.9 (C11), 134.6 (C13a), 141.2 (C9a), 145.0 (C4a),
159.6 (C7), 171.9 (C3).
MS (EI, 70 eV): m/z (%) = 325 (37) [M+], 296 (13), 278 (8), 251
(11), 250 (12), 236 (14), 222 (100).
Anal. Calcd for C19H19NO2S: C, 70.12; H, 5.88; N, 4.30. Found: C,
70.21; H, 5.80; N, 4.25.

21.3 (11-CH3), 33.5 (C2), 41.9 (C9), 64.4 (C13b), 124.3 (C8), 125.4
(C10), 126.9 (C6), 127.2 (C12), 127.9 (C7), 128.3 (C5), 128.4
(C13), 131.1 (C13a), 135.2 (C8a), 138.5 (C11), 141.0 (C9a), 143.4
(C4a), 171.6 (C3).
MS (EI, 70 eV): m/z (%) = 309 (55) [M+], 280 (56), 262 (12), 235
(15), 234 (34), 220 (22), 206 (100).
73.82; H, 6.30; N, 4.44.
7-Chloro-9-ethyl-12-methyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-one (5g)
Time: 35 h; yellow viscous oil; yield: 50%.
(CN).
1
2.25 (s, 3 H, 12-CH3), 2.202.35 (m, 2 H, 14-CH2), 3.63 (d, J = 15.4
Hz, 1 H, H2A), 3.98 (dd, J = 15.4, 2.0 Hz, 1 H, H2B), 4.30 (t, J = 7.6
Hz, 1 H, H9), 6.15 (s, 1 H, H13b), 6.90 (s, 1 H, H13), 7.07 (d, J = 8.0
Hz, 1 H, H11), 7.20 (d, J = 8.0 Hz, 1 H, H10), 7.237.31 (m, 3 H,
H5, H6, H8).
13

22.8 (12-CH3), 33.6 (C2), 41.8 (C9), 64.5 (C13b), 124.9 (C10),
125.0 (C5), 127.2 (C6), 128.8 (C8), 129.4 (C11), 129.7 (C13), 133.9
(C8a), 134.1 (C13a), 134.4 (C7), 136.8 (C12), 137.4 (C9a), 145.7
(C4a), 171.8 (C3).
MS (EI, 70 eV): m/z (%) = 343 (35Cl, 39) [M+], 314 (69), 296 (9),
269 (10), 268 (17), 254 (18), 240 (100).
Anal. Calcd for C19H18ClNOS: C, 66.36; H, 5.28; N, 4.07. Found:
C, 66.50; H, 5.13; N, 3.98.
9-Ethyl-7,11-dimethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5h)
(CN).
1
2.30 (s, 6 H, 7-CH3, 11-CH3), 2.202.38 (m, 2 H, 14-CH2), 3.62 (dd,
J = 15.5, 0.7 Hz, 1 H, H2A), 3.97 (dd, J = 15.5, 2.0 Hz, 1 H, H2B),
4.33 (t, J = 7.6 Hz, 1 H, H9), 6.19 (s, 1 H, H13b), 6.94 (d, J = 7.8
Hz, 1 H, H12), 6.97 (d, J = 7.8 Hz, 1 H, H13), 7.07 (s, 1 H, H8), 7.08
(d, J = 6.6 Hz, 1 H, H5), 7.13 (s, 1 H, H10), 7.21 (dd, J = 6.6, 2.0
Hz, 1 H, H6).
13
21.8 (7-CH3), 21.9 (11-CH3), 33.9 (C2), 42.2 (C9), 64.8 (C13b),
125.4 (C8), 125.8 (C10), 127.6 (C12), 128.0 (C5, C6), 128.9 (C13),
131.7 (C13a), 133.0 (C8a), 138.7 (C7), 138.9 (C11), 141.6 (C9a),
143.6 (C4a), 172.1 (C3).
MS (EI, 70 eV): m/z (%) = 323 (36) [M+], 294 (43), 276 (10), 249
(11), 248 (24), 234 (19), 220 (100).
9-Ethyl-11-methyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5f)

74.11; H, 6.70; N, 4.26.
(CN).
9-Ethyl-7,12-dimethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2a]azepin-3(2H)-one (5i)

2.222.38 (m, 2 H, 14-CH2), 2.32 (s, 3 H, 11-CH3), 3.63 (d, J = 15.5
Hz, 1 H, H2A), 3.98 (dd, J = 15.5, 1.8 Hz, 1 H, H2B), 4.37 (t, J = 7.6
Hz, 1 H, H9), 6.21 (s, 1 H, H13b), 6.94 (d, J = 7.8 Hz, 1 H, H12),
(CN).
1
2.24 (s, 3 H, 12-CH3), 2.212.35 (m, 2 H, 14-CH2), 2.31 (s, 3 H, 7-
PAPER
CH3), 3.63 (dd, J = 15.5, 0.7 Hz, 1 H, H2A), 3.98 (dd, J = 15.5, 2.0
Hz, 1 H, H2B), 4.29 (t, J = 7.6 Hz, 1 H, H9), 6.15 (s, 1 H, H13b),
6.88 (s, 1 H, H13), 7.04 (dd, J = 7.8, 1.0 Hz, 1 H, H6), 7.05 (br s, 1
H, H8), 7.06 (d, J = 8.0 Hz, 1 H, H11), 7.19 (d, J = 7.8 Hz, 1 H, H5),
7.21 (d, J = 8.0 Hz, 1 H, H10).
13
20.9 (14-CH2), 21.6 (7-CH3), 33.6 (C2), 41.7 (C9), 64.6 (C13b),
124.8 (C10), 125.1 (C8), 127.7 (C5, C6), 129.3 (C13), 129.4 (C11),
132.7 (C7), 134.4 (C13a), 136.4 (C12), 138.4 (C9a), 138.6 (C8a),
143.5 (C4a), 171.8 (C3).
MS (EI, 70 eV): m/z (%) = 323 (45) [M+], 294 (92), 276 (10), 249
(10), 248 (20), 234 (16), 220 (100).
74.20; H, 6.49; N, 4.30.
(8)
Acknowledgment
The authors would like to acknowledge for the financial support due
by the Colombian Institute for Science and Research (COLCIENCIAS, Grant No 1102-408-20563). A.P. also thanks Dr. E. Stashenko (Laboratory of Chromatography, School of Chemistry,
Industrial University of Santander) for providing GC-MS spectra.
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PAPER
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A Simple and Practical Approach To The Dibenzo (C, F) Thiazolo (3,2-A) Azepines: A Novel Fused Tetracyclic Azepine System

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A Simple and Practical Approach To The Dibenzo (C, F) Thiazolo (3,2-A) Azepines: A Novel Fused Tetracyclic Azepine System

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A Simple and Practical Approach to the Dibenzo[c,f]thiazolo[3,2-a]azepines:

no prior literature reports that describe the fusion of the

Key words: amino-Claisen rearrangement, intramolecular Friedel

The dibenz[b,e]azepine ring is a commonly observed

Molecular structures of some bioactive-fused tetracyclic

Among the classical methodologies, the intramolecular

ortho-Amino-substituted allylarenes in the construction of dihydrodibenz[b,e]azepine and dihydrobenzo[e]naphth[b]azepine rings

Retrosynthetic analysis of title compounds 5

To the best of our knowledge, the facile construction of

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nilines were transferred, through a 7-exo-trig cyclization

Table 1 Preparation of Dihydromorphanthridines 3 by Intramolecular FriedelCrafts Alkylation of Substituted 2-Allylanilines 2 with

The obtained results indicated that the cyclization reaction

It should also be noted that in the cases of 2g and 2i with

Figure 2 Wheland complexes A and B as potential intermediates in

Yields are for isolated, chromatographically pure products.

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nals in the aliphatic region (triplet for H11, d = 3.693.58,

Synthesis 2010, No. x, AL

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signed for methylene (C2), methine (C13b) and carbonyl

H NMR (400 MHz, CDCl3): d = 3.37 (d, J = 6.0 Hz, 2 H,

C NMR (100 MHz, CDCl3): d = 36.5 (CH2CH=), 48.2 (NCH2),

H NMR (400 MHz, CDCl3): d = 3.32 (d, J = 6.4 Hz, 2 H,

C NMR (100 MHz, CDCl3): d = 36.2 (CH2CH=), 48.7 (NCH2),

H NMR (400 MHz, CDCl3): d = 3.29 (d, J = 6.0 Hz, 2 H,

C NMR (100 MHz, CDCl3): d = 36.1 (CH2CH=), 48.2 (NCH2),

H NMR (400 MHz, CDCl3): d = 2.35 (s, 3 H, 4-CH3), 3.40 (d,

C NMR (100 MHz, CDCl3): d = 20.5 (4-CH3), 36.6 (CH2CH=),

H NMR (400 MHz, CDCl3): d = 3.35 (d, J = 6.0 Hz, 2 H,

H NMR (400 MHz, CDCl3): d = 2.43 (s, 3 H, 4-CH3), 3.39 (d,

C NMR (100 MHz, CDCl3): d = 21.2 (4-CH3), 36.6 (CH2CH=),

H NMR (400 MHz, CDCl3): d = 2.40 (s, 3 H, 3-CH3), 3.31 (d,

Synthesis 2010, No. x, AL

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C NMR (100 MHz, CDCl3): d = 21.5 (3-CH3), 36.2 (CH2CH=),

H NMR (400 MHz, CDCl3): d = 2.33 (s, 3 H, 4-CH3), 2.42 (s, 3 H,

H NMR (400 MHz, CDCl3): d = 2.29 (s, 3 H, 4-CH3), 2.38 (s, 3 H,

C NMR (100 MHz, CDCl3): d = 20.6 (4-CH3), 21.7 (3-CH3), 36.7

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with CH2Cl2 (3 50 mL). The combined organic extracts were

C NMR (100 MHz, CDCl3): d = 12.9 (13-CH3), 30.8 (12-CH2),

C NMR (100 MHz, CDCl3): d = 13.1 (13-CH3), 20.5 (2-CH3),

H NMR (400 MHz, CDCl3): d = 0.94 (t, J = 7.4 Hz, 3 H, 13-CH3),

C NMR (100 MHz, CDCl3): d = 13.2 (13-CH3), 20.5 (2-CH3),

Anal. Calcd for C18H21N: C, 86.01; H, 8.42; N, 5.57. Found: C,

Anal. Calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found: C,

Anal. Calcd for C18H21N: C, 86.01; H, 8.42; N, 5.57. Found: C,

Anal. Calcd for C17H19N: C, 86.03; H, 8.07; N, 5.90. Found: C,

11-Ethyldibenz[b,e]azepines 4; General Procedure

Synthesis 2010, No. x, AL

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H NMR (400 MHz, CDCl3): d = 0.70 (t, J = 7.4 Hz, 3 H, 13-CH3),

C NMR (100 MHz, CDCl3): d = 12.5 (13-CH3), 24.2 (12-CH2),

H NMR (400 MHz, CDCl3): d = 0.69 (t, J = 7.4 Hz, 3 H, 13-CH3),

Anal. Calcd for C16H14FN: C, 80.31; H, 5.90; N, 5.85. Found: C,

C NMR (100 MHz, CDCl3): d = 12.6 (13-CH3), 24.2 (12-CH2),

C NMR (100 MHz, CDCl3): d = 12.6 (13-CH3), 21.5 (9-CH3),