Ring-closing metathesis approach to 2 H -2-benzazepine-1,3-diones

Article abstract of DOI:10.1055/s-0030-1258416

A series of diversely substituted 2H-2-benzazepine-1,3-diones were efficiently prepared from the unsaturated precursors, N-acyl-o-vinylbenzamides, through a ring-closing metathesis reaction. The parent compounds were easily obtained from the appropriate o

Full text of DOI:10.1055/s-0030-1258416

PAPER
669
Ring-Closing Metathesis Approach to 2H-2-Benzazepine-1,3-diones
Synthesis of
a
2
t
-2-Be
é
nzazepine-
p
1,3-dione
s
hane Lebrun,a,b Axel Couture,*a,c Eric Deniau,a,b Pierre Grandclaudona,b
Université Lille Nord de France, 59000 Lille, France
Fax +33(3)20436309; E-mail: axel.couture@univ-lille1.fr
b
c
USTL, Laboratoire de Chimie Organique Physique, EA CMF 4478, Bâtiment C3(2), 59655 Villeneuve d’Ascq Cedex, France
CNRS, UMR 8181 ‘UCCS’, Bâtiment C3(2), 59655 Villeneuve d’Ascq Cedex, France
Received 1 December 2010; revised 9 December 2010
general synthetic methods for their elaboration. To the
best of our knowledge, compounds structurally related to
1a–f have only been obtained by N-alkylation of the cor-
responding NH-free models derived from PPA-induced
annulation of cis-cinnamonitrile-o-carboxylic acid deriv-
atives.6 The latter compounds have been prepared by
inverse Beckmann rearrangement of b-nitroso-a-naph-
thols.7 This ring-expansion methodology is fraught with
difficulties associated with the use of hazardous reagents
and its applicability is unsatisfactory mainly because of
restrictions in the choice of substituents on the aromatic
unit and the seven-membered ring system as well. Addi-
tionally the N-phenyl derivative of a bare model has been
incidentally obtained through condensation of triphe-
nyl(phenyliminovinylidene)phosphorane with phthal-
aldehydic acid.8
Abstract: A series of diversely substituted 2H-2-benzazepine-1,3-
diones were efficiently prepared from the unsaturated precursors,
N-acyl-o-vinylbenzamides, through a ring-closing metathesis reac-
tion. The parent compounds were easily obtained from the appropri-
ate o-vinylbenzoic acids.
Key words: fused-ring systems, acylation, ring closure, metathesis,
imides
Benzo-fused heterocyclic ring systems have received a lot
of attention over the years because of their ubiquitous ap-
pearance in natural products and modern pharmaceuti-
cals.1 2-Benzazepines and their oxo derivatives at
different oxidation levels fall into this category. They are
a class of benzo-fused nitrogen-containing seven-mem-
bered heterocyclic rings, which are important structural
features of marketed drugs, clinical candidates, and other
bioactive molecules.2 As a consequence, the development
of synthetic methodologies that may have generality for
the construction of multifarious substituted and unsubsti-
tuted benzazepines is an area of current interest and alter-
native methods are currently the object of synthetic
endeavor. In this context we envisioned the assembly of
the corresponding a,b-unsaturated oxobenzolactams, that
is, the 2H-2-benzazepine-1,3-diones 1a–f (Figure 1). It
was anticipated that these highly functionalized models
could serve a key role as advanced intermediates prior to
the conversion to tailor-made environmentally different
benzazepine derivatives as they possess the requisite
structure and functional groups location to be easily con-
verted into seven-membered azaheterocyclic models. We
surmised that ensuing rather simple chemical manipula-
tion of the latent functionalities would allow for rapid
achievement of molecular complexity in a highly efficient
manner. Noteworthy compounds of this class are en-
dowed with interesting chemotherapeutic properties.
They have indeed been found to be CNS stimulants, in
vitro antimicrobial agents and to induce motor activity.3
They are also known to display potent inhibitory activity
against cyclic adenosine phosphodiesterase and to act as
sunscreen agents.4 In contrast, the use of benzazepines
with an unsaturation in the heterocyclic ring has seen very
little synthetic application,5 probably due to the lack of
R1
H
H
R2
H
H
R3 R4
1
a
b
c
d
e
f
O
R3
Me
Pr
Bn
H
H
H
H
H
R1
R2
N
H
H
O
MeO MeO Me
Me
OCH2O
OCH2O
R4
Me Me
Figure 1 Targeted 2H-2-benzazepine-1,3-diones 1a–f
Herein we wish to report a conceptually new synthetic ap-
proach to a variety of 2H-2-benzazepine-1,3-diones 1a–f
based upon the ultimate creation of the alkene moiety em-
bedded in the azaheterocyclic unit on reliance with the
ring-closing metathesis (RCM) strategy. Olefin RCM re-
action has become a powerful tool in organic synthesis
over the past decades, especially when well-characterized
ruthenium catalysts were employed.9 RCM reaction,
which ranks high in the hierarchy of synthetic approaches
for the elaboration of small, medium, and large unsaturat-
ed heterocycles, is now routinely applied to ensure the as-
sembly of cyclic olefins of virtually all ring sizes
containing ether, ester, amide, amine, and other function-
alities.10 However as far as we know, this annulation tech-
nique has not been applied to N-acylamide derivatives.
One way of constructing the targeted compounds 1a–f
would be by cyclization of the polyenic diacylamines 2a–f
as suitable precursors for the planned RCM reaction. The
assembly of these highly functionalized opened models
was envisioned and the first facet of the synthesis was the
elaboration of the NH-free amides 3a–e, which were
SYNTHESIS 2011, No. 4, pp 0669–0673
x
x
.
x
x
.2
0
1
1
Advanced online publication: 19.01.2011
DOI: 10.1055/s-0030-1258416; Art ID: Z30110SS
© Georg Thieme Verlag Stuttgart · New York

670
S. Lebrun et al.
PAPER
readily obtained under standard conditions from the cor- it was pleasing to observe that the yield could be increased
responding benzoic acids 4–6 (Scheme 1, Table 1). to 75% when the N-acylated o-vinylbenzamide 2a was
Deprotonation of 3a–e with sodium hydride and subse- subjected to 5 mol% of the thermally more stable second-
quent interception of the transient sodium amide salt with generation Grubbs catalyst (10) under reflux in toluene,
a suitably (un)substituted acryloyl chloride 7, 8 delivered which turned out to be the best solvent. These optimal
quite satisfactory yields of the unsaturated N-acyl-o-vi- conditions were then used to perform the annulation reac-
nylbenzamides 2a–f (Scheme 1, Table 1).
tion of the structurally diverse styrene precursors 2b–f. A
representative series of compounds, which have been pre-
pared by this technique are presented in Table 1, where it
can be seen that this simple procedure affords very satis-
factory yields of the targeted 2H-2-benzazepine-1,3-di-
ones 1a–f. The method tolerates the presence of diverse
substituents on the aromatic unit and on the diacylated ni-
trogen atom as well. In strong contrast with the sole re-
ported method for the synthesis of such compounds
incorporation of substituents on the alkene moiety could
also be envisaged owing to the availability of appropriate
acryloyl chlorides, as exemplified by the efficient forma-
tion of the substituted model 1f by RCM reaction applied
to 2f.
1. (COCl)2, toluene–DMF
r.t., 2 h
O
O
R3
2. R3NH2, Et3N, CH2Cl2
r.t., 4 h
R1
R2
OH
R1
R2
N
H
70–85%
4–6
3a–e
1. NaH, THF
r.t., 30 min
2. R4
O
O
R3
7, 8
Cl
R1
R2
–78 °C to r.t., 5 h
N
O
58–70%
R4
2a–f
N
N
Mes
Mes
Ph
O
PCy3
Ru
R3
Ph
Cl
Cl
Cl
Grubbs II catalyst (5 mol%)
toluene, reflux, 5 h
R1
R2
Ru
N
Cl
PCy3
9
PCy3
10
O
69–81%
R4
Figure 2 Common ruthenium catalysts used in RCM reactions
1a–f
Scheme 1 Synthesis of titled 2H-2-benzazepine-1,3-diones 1a–f
In summary, we have devised a short and efficient syn-
thetic strategy towards a variety of hitherto hardly acces-
sible 2H-2-benzazepine-1,3-diones. The key step of the
synthetic sequence is based upon the creation of the alk-
ene moiety present in the azepinedione template in the ul-
timate step via unprecedented RCM reaction.
This technique gives rise to a number of a,b-unsaturated
oxolactam-type models, which can be regarded as versa-
tile building blocks with the capacity to incorporate addi-
The targeted imides 1a–f were only one reaction away
from the precursors 2a–f. Thus, the ring-closing metathe-
sis experiments was undertaken next and for this purpose
the first- and second-generation Grubbs catalysts 9 and 10
were screened (Figure 2). At first, the seven-membered
ring precursor 2a underwent ring closure after heating un-
der reflux in CH2Cl2 for 24 hours using 5 mol% first-gen-
eration Grubbs catalyst (9; reaction monitored by TLC);
however, the benzazepinedione 1a was isolated only in a
moderate yield (32%). Increasing the amount of the same
catalyst to 10 mol% had no significant impact on the
process efficiency (35% vs. 32% yield for 1a). However,
tional substituents/functionalities at
a later stage.
Applications of this strategy to highly substituted benza-
zepines synthesis are underway and will be reported in
due course.
Table 1 Compounds 3a–e, 2a–f and 1a–f Prepared
NH-Free o-vinylbenzamide 3
Acryloyl chloride 7, 8 N-Acyl-o-vinylbenzamide 2H-2-Benzazepine-1,3-dione
2
1
R1
R2
H
R3
Yield (%)
R4
H
Yield (%)
Yield (%)
3a
3b
3c
3d
3e
3e
H
Me
Pr
70
76
85
75
82
–
7
7
7
7
7
8
2a
2b
2c
2d
2e
2f
70
66
60
63
65
58
1a
1b
1c
1d
1e
1f
75
69
81
72
78
70
H
H
H
H
H
Bn
Me
Me
Me
H
OMe
OCH2O
OCH2O
OMe
H
H
Me
Synthesis 2011, No. 4, 669–673 © Thieme Stuttgart · New York

PAPER
Synthesis of 2H-2-Benzazepine-1,3-dione
671
All solvents were dried and distilled according to standard proce-
dures. Dry glassware was obtained by oven-drying and assembling
under dry argon. The glassware was equipped with rubber septa and
reagent transfer was performed by syringe techniques. For flash
chromatography, Merck silica gel 60 (40–63 mm, 230–400 mesh
ASTM) was used. The melting points were obtained on a Reichert-
Thermopan apparatus and are not corrected. Elemental analyses
were obtained using a Carlo-Erba CHNS-11110 equipment. NMR
spectra were recorded on a Bruker AM 300 spectrometer (300 MHz
and 75 MHz, for 1H, and 13C) with CDCl3 as solvent and Me4Si as
internal standard.
NH-Free o-Vinybenzamides 3a–e; General Procedure
A mixture of benzoic acid derivative 4–6 (20 mmol), oxalyl chlo-
ride (50 mmol), and DMF (0.5 mL) in freshly distilled toluene (40
mL) was stirred for 2 h at r.t.. The solvent was removed under vac-
uum and the residue was dissolved in CH2Cl2 (10 mL). The solution
was added dropwise to a solution of amine R3NH2 (20 mmol) and
Et3N (40 mmol) in CH2Cl2 (30 mL) at 0 °C, then the mixture was
stirred at r.t. for 4 h. H2O (30 mL) was added and the mixture was
extracted with CH2Cl2 (2 × 30 mL). The combined organic layers
were dried (MgSO4) and the solvent was removed under vacuum.
Benzamides 3a–e were purified by flash column chromatography
on silica gel using EtOAc–hexanes (80:20) as eluent and finally re-
crystallized from hexane–toluene (Tables 1 and 2).
The o-vinylbenzoic acids 4,11 5,12 12 were prepared following liter-
6
ature procedures.
N-Eneacyl-o-vinylbenzamides 2a–f; General Procedure
4,5-Dimethoxy-2-vinylbenzoic Acid (5)
A solution of benzamide 3a–e (4.5 mmol) in anhyd THF (5 mL) was
added dropwise to a suspension of NaH (5.4 mmol) in anhyd THF
(20 mL) at 0 °C. The reaction mixture was stirred for 30 min at r.t.
and cooled to –78 °C. The appropriate acryloyl chloride 7, 8 (9
mmol) was then added dropwise. After stirring for 5 min at –78 °C,
the mixture was allowed to warm to r.t. over 5 h. H2O (10 mL) was
added and the mixture was extracted with CH2Cl2 (2 × 30 mL). The
combined extracts were dried (MgSO4) and the solvent was re-
moved under vacuum. The residue was purified by flash column
chromatography on silica gel using EtOAc–hexanes (10:90) as elu-
ent to afford N-acylamides 2a–f as yellow oils (Tables 1 and 2).
Mp 183–185 °C (Lit.13 mp 183–184 °C).
1H NMR (300 MHz, CDCl3): d = 3.94 (s, 3 H, OCH3), 3.98 (s, 3 H,
OCH3), 5.32 (d, J = 10.9 Hz, 1 Hvinyl), 5.59 (d, J = 17.4 Hz, 1 Hvinyl),
7.05 (s, 1 Harom), 7.57 (s, 1 Harom), 7.64 (dd, J = 10.9, 17.4 Hz, 1 Hvinyl).
13C NMR (75 MHz, CDCl3): d = 56.0 (2 × OCH3), 109.6 (CH2),
113.4 (CH), 115.4 (CH), 119.2 (C), 135.6 (C), 136.2 (CH), 148.0
(C), 152.7 (C), 172.4 (C=O).
6-Vinylbenzo[1,3]dioxole-5-carboxylic Acid (6)
Mp 165–167 °C (Lit.12 mp 163–164 °C).
1H NMR (300 MHz, DMSO-d6): d = 5.22 (d, J = 11.0 Hz, 1 Hvinyl),
5.65 (d, J = 17.5 Hz, 1 Hvinyl), 6.10 (s, 2 H, OCH2O), 7.20 (s, 1
2H-2-Benzazepine-1,3-diones 1a–f; General Procedure
A solution of N-acylamide 2a–f (1.5 mmol) and second-generation
Grubbs catalyst (0.075 mmol, 5 mol%) in anhyd toluene (20 mL)
was refluxed under stirring for 5 h under argon (monitored by TLC
to establish completion of the reaction). The reaction mixture was
concentrated under vacuum and the resulting residue was purified
by flash column chromatography on silica gel using EtOAc–
hexanes (30:70) as eluent to furnish 2H-2-benzazepine-1,3-diones
1a–f as yellow oils (Tables 1 and 2).
Harom), 7.28 (s, 1 Harom), 7.46 (dd, J = 11.0, 17.5 Hz, 1 Hvinyl), 12.85
(br s, 1 H, CO2H).
13C NMR (75 MHz, DMSO-d6): d = 101.9 (OCH2O), 105.8 (CH),
109.3 (CH), 115.2 (CH2), 123.0 (C), 134.5 (C), 134.9 (CH), 146.7
(C), 150.4 (C), 167.6 (C=O).
Table 2 Physical and Spectroscopic Data of Carboxamides 3a–e, N-Eneacylamides 2a–f, and Benzazepinediones 1a–f Prepared
Producta Mp (°C) 1H NMR (CDCl3/TMS) d, J (Hz) 13C NMR (CDCl3/TMS) d
3a
125–127
2.98 (d, J = 5.0 Hz, 3 H, NCH3), 5.34 (dd, J = 1.0, 11.0 Hz, 1 Hvinyl), 26.8 (NCH3), 116.7 (CH2), 126.2 (CH), 127.4
(123–124)14 5.71 (dd, J = 1.0, 17.5 Hz, 1 Hvinyl), 5.85 (br s, 1 H, NH), 7.02 (dd, (CH), 127.7 (CH), 130.1 (CH), 134.5 (CH),
J = 11.0, 17.5 Hz, 1 Hvinyl), 7.24–7.31 (m, 1 Harom), 7.35–7.44 (m, 2 135.7 (C), 150.6 (C), 171.5 (C=O)
Harom), 7.56 (d, J = 7.7 Hz, 1 Harom
)
3b
62–64
0.97 (t, J = 7.4 Hz, 3 H, CH3), 1.62 (quint, J = 7.4 Hz, 2 H), 3.38
11.5 (CH3), 22.8 (CH2), 41.7 (NCH2), 116.6
(62–63)14
(m, 2 H, NCH2), 5.33 (d, J = 10.9 Hz, 1 Hvinyl), 5.69 (d, J = 17.4 Hz, (CH2), 126.1 (CH), 127.4 (CH), 127.7 (CH),
1 Hvinyl), 5.98 (br s, 1 H, NH), 7.04 (dd, J = 10.9, 17.5 Hz, 1 Hvinyl), 130.0 (CH), 134.5 (CH), 135.6 (C), 135.7 (C),
7.21–7.28 (m, 1 Harom), 7.34–7.45 (m, 2 Harom), 7.56 (d, J = 7.8 Hz, 169.4 (C=O)
1 Harom
)
3c
3d
3e
88–90
4.58 (d, J = 5.8 Hz, 2 H, NCH2), 5.12 (d, J = 11.0 Hz, 1 Hvinyl), 5.71 43.9 (NCH2), 116.6 (CH2), 126.1 (CH), 127.4
(88–89)14
(d, J = 17.5 Hz, 1 Hvinyl), 6.55 (br s, 1 H, NH), 7.06 (dd, J = 11.0,
17.5 Hz, 1 Hvinyl), 7.25–7.53 (m, 8 Harom), 7.82 (d, J = 7.6 Hz, 1
(CH), 127.6 (CH), 128.0 (2 × CH), 128.3 (2 ×
CH), 130.1 (CH), 131.9 (CH), 134.5 (CH), 135.4
(C), 137.4 (C), 138.3 (C), 169.5 (C=O)
Harom
)
140–142
(colorless
crystals)
2.96 (d, J = 4.8 Hz, 3 H, NCH3), 3.87 (s, 3 H, OCH3), 3.92 (s, 3 H, 26.8 (NCH3), 55.9 (OCH3), 56.0 (OCH3), 108.5
OCH3), 5.28 (d, J = 10.9 Hz, 1 Hvinyl), 5.59 (d, J = 17.4 Hz, 1 Hvinyl), (CH2), 110.5 (CH), 115.2 (CH), 127.9 (C), 129.0
6.02 (br s, 1 H, NH), 6.97 (s, 1 Harom), 7.00 (s, 1 Harom), 7.02 (dd,
J = 10.9, 17.4 Hz, 1 Hvinyl
(C), 134.5 (CH), 140.4 (C), 150.2 (C), 169.6
(C=O)
)
136–138
(colorless
crystals)
2.93 (d, J = 4.8 Hz, 3 H, NCH3), 5.23 (dd, J = 0.9, 10.9 Hz, 1 Hvinyl), 26.8 (NCH3), 101.6 (OCH2O), 105.7 (CH), 107.5
5.54 (dd, J = 0.9, 17.9 Hz, 1 Hvinyl), 5.92 (s, 2 H, OCH2O), 6.03 (br (CH), 115.0 (CH2), 129.6 (C), 130.8 (C), 134.1
s, 1 H, NH), 6.86 (s, 1 Harom), 6.89 (dd, J = 10.9, 17.4 Hz, 1 Hvinyl), (CH), 147.1 (C), 149.1 (C), 169.4 (C=O)
6.97 (s, 1 Harom
)
Synthesis 2011, No. 4, 669–673 © Thieme Stuttgart · New York

672
S. Lebrun et al.
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Table 2 Physical and Spectroscopic Data of Carboxamides 3a–e, N-Eneacylamides 2a–f, and Benzazepinediones 1a–f Prepared (continued)
Producta Mp (°C) 1H NMR (CDCl3/TMS) d, J (Hz) 13C NMR (CDCl3/TMS) d
2a
2b
2c
oil
oil
oil
3.21 (s, 3 H, NCH3), 5.39 (dd, J = 0.9, 11.0 Hz, 1 Hvinyl), 5.56 (dd, 32.8 (NCH3), 118.0 (CH2), 126.3 (CH), 127.6
J = 1.8, 10.1 Hz, 1 Hvinyl), 5.74 (dd, J = 0.9, 17.3 Hz, 1 Hvinyl), 6.27 (CH), 128.0 (CH), 128.7 (CH2), 130.6 (CH),
(dd, J = 1.8, 16.8 Hz, 1 Hvinyl), 6.46 (dd, J = 10.1, 16.8 Hz, 1 Hvinyl), 131.0 (CH), 133.1 (CH), 134.9 (C), 135.9 (C),
6.83 (dd, J = 11.0, 17.3 Hz, 1 Hvinyl), 7.24–7.32 (m, 2 Harom), 7.42– 169.2 (C=O), 172.9 (C=O)
7.49 (m, 1 Harom), 7.58 (d, J = 7.9 Hz, 1 Harom
)
0.88 (t, J = 7.4 Hz, 3 H, CH3), 1.64 (quint, J = 7.4 Hz, 2 H), 3.70– 11.4 (CH3), 22.1 (CH2), 47.3 (NCH2), 117.8
3.75 (m, 2 H, NCH2), 5.41 (dd, J = 0.9, 11.0 Hz, 1 Hvinyl), 5.45–5.50 (CH2), 126.2 (CH), 127.7 (CH), 127.8 (CH),
(m, 1 Hvinyl), 5.73 (dd, J = 0.9, 17.4 Hz, 1 Hvinyl), 6.15–6.27 (m, 2
Hvinyl), 6.88 (dd, J = 11.0, 17.4 Hz, 1 Hvinyl), 7.25–7.29 (m, 2 Harom), (CH), 135.2 (C), 136.3 (C), 169.2 (C=O), 173.0
7.41–7.47 (m, 1 Harom), 7.59 (d, J = 7.9 Hz, 1 Harom (C=O)
128.2 (CH2), 130.9 (CH), 131.1 (CH), 133.2
)
5.03 (s, 2 H, NCH2), 5.32 (dd, J = 0.9, 10.9 Hz, 1 Hvinyl), 5.45 (dd, 48.6 (NCH2), 117.9 (CH2), 126.3 (CH), 127.6
J = 5.0, 6.7 Hz, 1 Hvinyl), 5.70 (dd, J = 0.9, 17.4 Hz, 1 Hvinyl), 6.18– (CH), 127.7 (CH), 128.0 (CH), 128.4 (2 × CH),
6.26 (m, 2 Hvinyl), 6.79 (dd, J = 10.9, 17.4 Hz, 1 Hvinyl), 7.25–7.58 128.5 (2 × CH), 128.7 (CH2), 130.7 (CH), 131.3
(m, 9 Harom
)
(CH), 133.1 (CH), 134.9 (C), 136.6 (C), 137.1
(C), 169.3 (C=O), 172.9 (C=O)
2d
2e
oil
oil
3.21 (s, 3 H, NCH3), 3.85 (s, 3 H, OCH3), 3.92 (s, 3 H, OCH3), 5.27 32.8 (NCH3), 56.0 (OCH3), 56.1 (OCH3), 108.3
(d, J = 10.9 Hz, 1 Hvinyl), 5.48 (dd, J = 1.6, 9.7 Hz, 1 Hvinyl), 5.58 (d, (CH), 110.6 (CH), 116.3 (CH2), 127.0 (C), 128.2
J = 17.2 Hz, 1 Hvinyl), 6.22–6.31 (m, 2 Hvinyl), 6.75 (dd, J = 10.9,
17.2 Hz, 1 Hvinyl), 6.80 (s, 1 Harom), 6.98 (s, 1 Harom
(CH2), 130.3 (CH), 130.4 (C), 132.9 (CH), 148.8
(C), 151.3 (C), 169.2 (C=O), 172.8 (C=O)
)
3.23 (s, 3 H, NCH3), 5.29 (d, J = 11.2 Hz, 1 Hvinyl), 5.56 (dd, J = 1.7, 32.9 (NCH3), 101.9 (OCH2O), 105.9 (CH), 107.7
10.1 Hz, 1 Hvinyl), 5.61 (d, J = 17.2 Hz, 1 Hvinyl), 6.05 (s, 2 H,
OCH2O), 6.24 (dd, J = 1.9, 16.8 Hz, 1 Hvinyl), 6.42 (dd, J = 10.1,
16.8 Hz, 1 Hvinyl), 6.75 (dd, J = 11.2, 17.2 Hz, 1 Hvinyl), 6.80 (s, 1
(CH), 116.6 (CH2), 128.5 (CH2), 128.7 (C),
130.5 (CH), 132.0 (C), 132.7 (CH), 147.5 (C),
150.3 (C), 169.1 (C=O), 172.5 (C=O)
Harom), 7.03 (s, 1 Harom
)
2f
oil
1.62 (s, 3 H, CH3), 3.35 (s, 3 H, NCH3), 5.13 (s, 1 Hvinyl), 5.21 (s, 1 18.3 (CH3), 32.8 (NCH3), 101.9 (OCH2O), 105.9
Hvinyl), 5.28 (d, J = 10.9 Hz, 1 Hvinyl), 5.57 (d, J = 17.3 Hz, 1 Hvinyl), (CH), 108.1 (CH), 116.3 (CH2), 120.7 (CH2),
6.01 (s, 2 H, OCH2O), 6.67 (s, 1 Harom), 6.76 (dd, J = 10.9, 17.3 Hz, 127.5 (C), 132.5 (C), 133.3 (CH), 142.7 (C),
1 Hvinyl), 7.01 (s, 1 Harom
)
147.2 (C), 149.8 (C), 172.7 (C=O), 175.3 (C=O)
1a
1b
oil
oil
3.51 (s, 3 H, NCH3), 6.47 (d, J = 12.4 Hz, 1 Hvinyl), 7.07 (d, J = 12.4 33.3 (NCH3), 125.9 (CH), 130.7 (CH), 131.6
Hz, 1 Hvinyl), 7.42 (dd, J = 1.6, 7.3 Hz, 1 Harom), 7.55–7.67 (m, 2
Harom), 8.31 (dd, J = 1.7, 7.9 Hz, 1 Harom
(CH), 132.1 (C), 132.7 (CH), 133.6 (CH), 137.5
(C), 138.3 (CH), 165.8 (C=O), 168.1 (C=O)
)
0.95 (t, J = 7.4, 3 H, CH3), 1.69 (quint, J = 7.4, 2 H), 4.02–4.10 (m, 11.5 (CH3), 21.2 (CH2), 48.1 (NCH2), 126.4
2 H, NCH2), 6.42 (d, J = 12.4, 1 Hvinyl), 7.02 (d, J = 12.4, 1 Hvinyl), (CH), 130.5 (CH), 131.1 (CH), 132.1 (C), 132.5
7.38 (d, J = 7.3, 1 Harom), 7.51–7.62 (m, 2 Harom), 8.23 (d, J = 7.8, 1 (CH), 133.4 (CH), 133.5 (C), 137.7 (CH), 165.6
Harom
)
(C=O), 168.1 (C=O)
1c
oil
5.35 (s, 2 H, NCH2), 6.48 (d, J = 12.4 Hz, 1 Hvinyl), 7.06 (d, J = 12.4 49.2 (NCH2), 126.2 (CH), 127.3 (CH), 128.3 (2 ×
Hz, 1 Hvinyl), 7.21–7.33 (m, 3 Harom), 7.38–7.45 (m, 3 Harom), 7.53– CH), 128.4 (2 × CH), 130.7 (CH), 131.4 (CH),
7.66 (m, 2 Harom), 8.24 (dd, J = 0.9, 7.6 Hz, 1 Harom
)
132.2 (C), 132.8 (CH), 133.1 (C), 133.7 (CH),
137.4 (C), 138.2 (CH), 165.7 (C=O), 167.9
(C=O)
1d
1e
1f
oil
oil
oil
3.52 (s, 3 H, NCH3), 3.98 (s, 3 H, OCH3), 4.00 (s, 3 H, OCH3), 6.40 33.3 (N CH3), 56.2 (OCH3), 56.3 (OCH3), 113.3
(d, J = 12.4 Hz, 1 Hvinyl), 6.81 (s, 1 Harom), 6.97 (d, J = 12.4 Hz, 1
Hvinyl), 7.90 (s, 1 Harom
(CH), 115.5 (CH), 124.2 (CH), 126.1 (C), 126.9
(C), 138.1 (CH), 150.6 (C), 152.2 (C), 165.8
(C=O), 166.7 (C=O)
)
3.51 (s, 3 H, NCH3), 6.14 (s, 2 H, OCH2O), 6.40 (d, J = 12.5 Hz, 1 33.5 (NCH3), 102.7 (OCH2O), 114.4 (CH), 112.9
Hvinyl), 6.82 (s, 1 Harom), 6.93 (d, J = 12.5 Hz, 1 Hvinyl), 7.82 (s, 1
Harom
(CH), 124.3 (CH), 128.8 (C), 130.9 (C), 137.8
(CH), 147.1 (C), 151.2 (C), 165.6 (C=O), 166.8
(C=O)
)
2.25 (s, 3 H, CH3), 3.53 (s, 3 H, NCH3), 6.11 (s, 2 H, OCH2O), 6.75 23.3 (CH3), 34.1 (NCH3), 102.4 (OCH2O), 109.6
(s, 1 Harom), 6.96 (s, 1 Hvinyl), 7.69 (s, 1 Harom
)
(CH), 112.0 (CH), 126.5 (C), 128.8 (C), 130.4
(C), 134.7 (CH), 150.5 (C), 152.0 (C), 166.2
(C=O), 168.5 (C=O)
a Satisfactory microanalyses obtained for new compounds: C 0.29, H 0.26, N 0.29.
Synthesis 2011, No. 4, 669–673 © Thieme Stuttgart · New York

PAPER
Synthesis of 2H-2-Benzazepine-1,3-dione
673
(6) (a) Walker, G. N. J. Org. Chem. 1972, 37, 3955.
Acknowledgment
(b) Simchen, G. Angew. Chem., Int. Ed. Engl. 1968, 7, 464.
(c) Puar, M. S.; Vogt, B. R. Tetrahedron 1978, 34, 2887.
(7) Elvidge, J. A.; Jones, D. E. H. J. Chem. Soc. C 1967, 2059.
(8) (a) Bestmann, H. J.; Shade, G.; Schmid, G. Angew. Chem.,
Int. Ed. Engl. 1980, 19, 822. (b) Bestmann, H. J.; Shade, G.;
Luetke, H.; Moenius, T. Chem. Ber. 1985, 118, 2640.
(9) For reviews, see: (a) Donohoe, T. J.; Orr, A. J.; Bingham, M.
Angew. Chem. Int. Ed. 2006, 45, 2664. (b) Deiters, A.;
Martin, S. F. Chem. Rev. 2004, 104, 2199. (c)Grubbs, R. H.
In Handbook of Metathesis, Vol. 1-3; Wiley-VCH:
Weinheim, 2003.
(10) For selected reviews, see: (a) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413. (b) Hoveyda, A. H. Top.
Organomet. Chem. 1998, 1, 105. (c) Schrock, R. R.
Tetrahedron 1999, 55, 8141. (d) Phillips, A. J.; Abell, A. D.
Aldrichimica Acta 1999, 32, 75. (e) Fürstner, A. Angew.
Chem. Int. Ed. 2000, 39, 3012. (f) Hoveyda, A. H.; Schrock,
R. R. Chem. Eur. J. 2001, 7, 945. (g) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18. (h) Connon, S. J.;
Blechert, S. Angew. Chem. Int. Ed. 2003, 42, 1900.
(i) Grubbs, R. H. Tetrahedron 2004, 60, 7117. (j) Michaut,
A.; Rodriguez, J. Angew. Chem. Int. Ed. 2006, 45, 5740.
(k) Schrock, R. R. Angew. Chem. Int. Ed. 2006, 45, 3748.
(l) Grubbs, R. H. Angew. Chem. Int. Ed. 2006, 45, 3760.
(11) Howe, R. K.; Schleppnik, F. M. J. Heterocycl. Chem. 1982,
4, 721.
This research was supported by the Centre National de la Recherche
Scientifique, by MENESR and by the Program PRIM (Région
Nord-Pas de Calais).
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Synthesis 2011, No. 4, 669–673 © Thieme Stuttgart · New York