The synthesis of annulated azepin-3-one derivatives from 1,3,4-pentatrienyl nitrones by a heterocyclization - Rearrangement sequence

Article abstract of DOI:10.1002/1099-0690(200109)2001:17<3313::AID-EJOC3313>3.0.CO;2-E

Treatment of various o-propargylaryl nitrones of type 6 with potassium hydroxide or sodium methoxide in methanol at room temperature provides 1,2-dihydro[c]benzazepin-3-ones 9. The high product yields and the ease of the reactions under surprisingly mild conditions are particularly intriguing in view of the complex mechanistic pathway involved in the overall transformation. A mechanism based on a multistep rearrangement is proposed, involving conjugated allene nitrones of type 13 as precursors of a 1,7-dipolar cyclization process that is followed by further bond reorganizations, with cyclopropanones 16 as key intermediates. In agreement with the allene formation is the fact that the same transformation can be achieved with the triple bond isomers 12 and 37, which contain terminal alkyl groups. The intermediacy of cyclopropanones 16 is supported by the competing formation of the isoindoles 20 as minor products. On treatment of dihydronaphtho-annulated nitrones 30 with base, formation of the azepinones 31 as the main products is also accompanied by that of the isomeric isoindoles 32. Some selective C=O and C=C hydrogenation reactions, together with conversions into the thioketone 42 and the vinyl bromide 9p, have been demonstrated with representative examples of 9.

Full text of DOI:10.1002/1099-0690(200109)2001:17<3313::AID-EJOC3313>3.0.CO;2-E

FULL PAPER
The Synthesis of Annulated Azepin-3-one Derivatives from 1,3,4-Pentatrienyl
Nitrones by a Heterocyclization؊Rearrangement Sequence
Karin Knobloch,[a] Manfred Keller,[a][‡] and Wolfgang Eberbach*[a]
Dedicated to Professor Horst Prinzbach on the occasion of his 70th birthday
Keywords: Alkynes / Allenes / Dihydroazepinones / Electrocyclic reactions / Nitrones
Treatment of various o-propargylaryl nitrones of type 6 with
potassium hydroxide or sodium methoxide in methanol at
room temperature provides 1,2-dihydro[c]benzazepin-3-ones
the allene formation is the fact that the same transformation
can be achieved with the triple bond isomers 12 and 37,
which contain terminal alkyl groups. The intermediacy of
9. The high product yields and the ease of the reactions un- cyclopropanones 16 is supported by the competing formation
der surprisingly mild conditions are particularly intriguing in
of the isoindoles 20 as minor products. On treatment of dihy-
view of the complex mechanistic pathway involved in the dronaphtho-annulated nitrones 30 with base, formation of
overall transformation. A mechanism based on a multistep
rearrangement is proposed, involving conjugated allene
nitrones of type 13 as precursors of a 1,7-dipolar cyclization
process that is followed by further bond reorganizations, with
cyclopropanones 16 as key intermediates. In agreement with
the azepinones 31 as the main products is also accompanied
by that of the isomeric isoindoles 32. Some selective C=O and
C=C hydrogenation reactions, together with conversions into
the thioketone 42 and the vinyl bromide 9p, have been dem-
onstrated with representative examples of 9.
In the light of these results, the question arose of whether
1,3,4-pentatrienyl groups would similarly be suitable π-sys-
tems for 1,7-dipolar ring-closure reactions. Although the
use of allene units in pericyclic reactions is amply docu-
mented in the forms of intermolecular [2 2],[7,8]
Diels Alder,[7,8,9] and 1,3-dipolar cycloaddition reac-
tions,[10] there are still relatively few examples of their in-
volvement in electrocyclizations.[11] Conjugated nitrones of
type A may undergo three different cyclization processes:
the two intramolecular [4 2] cycloaddition alternatives re-
sulting in the formation of the bicyclic derivatives B and
C, respectively, and the 1,7-ring-closure affording the exo-
methyleneoxazepine D (Scheme 2). Here we report in detail
the results obtained with various benzo-, furo-, and alkeno-
annulated systems of type A.[12,13]
Introduction
Among the numerous heterocyclization methods, ring-
forming processes of conjugated 1,3-dipoles are of particu-
lar importance for the construction of five-membered ring
systems.[1] Over the past fifteen years, however, this meth-
odology has successfully been extended to the synthesis of
seven-membered heterocycles, using conjugated nitrile yl-
ides, nitrile imines, diazo compounds, carbonyl ylides, azo-
methine ylides, azomethine imines, and nitrones.[2] Espe-
cially valuable applications have been achieved with dipoles
of the latter type substituted by a butenynyl group.[3] The
behaviour of such dipolar 8π-species differs from that of
other systems, in which the primary ring products are un-
stable and undergo cleavage of the weak, newly created NO
bond (a latent functionality or ‘‘Sollbruchstelle’’),[4,5] fol-
lowed by several rearrangement steps. These finally end up
in the efficient formation of 2-acylpyrroles and/or α-pyri-
dones, respectively (Scheme 1).[3,6]
Scheme 2
Scheme 1
[a]
Institut für Organische Chemie und Biochemie der Universität
Freiburg
Results and Discussion
Albertstrasse 21, 79104 Freiburg, Germany
Fax: (internat.) 49-(0)761/203-6085
E-mail: eberbach@organik.chemie.uni-freiburg.de
For the construction of the cyclization precursors it is
necessary to consider three functionalities: the nitrone, the
[‡]
Crystal structure analyses.
Eur. J. Org. Chem. 2001, 3313 3332
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434 193X/01/0917 3313 $ 17.50 .50/0
3313

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
Scheme 3. Reagents: (i) HOCH2CH2OH, PTSA; (ii) a) nBuLi, b) MgBr2, c) BrCH2CϵCSiMe3; (iii) Bu4NHSO4, NH4Cl, KF; (iv) PTSA,
acetone/H2O; (v) ArI, PdCl2(PPh3)2, CuI, NEt3 or a) nBuLi, b) CH3I; (vi) CH3NHOH·HCl, NaOAc or PhNHOH, CH2Cl2
central (Z)-configured C C bond and the allene moiety. carried out by stirring solutions of the nitrones 6a o in
Whereas an aldehyde group is most convenient for the di- methanol in the presence of sodium methoxide or potas-
pole formation, and the required geometry of the double sium hydroxide. In most cases total consumption of the
bond is given by its incorporation in a cyclic system, there starting material was reached after 0.5 5.0 h, although 6f
are several procedures that might be appropriate for the and 6g required ca. 20 h for complete conversion. Careful
generation of the allene part.[7,8,14] Relying on the relative aqueous workup followed by flash chromatography of the
high kinetic stability of the nitrone function and the need reaction mixtures in each case afforded a single monomeric
for only small equilibrium concentrations of the allene iso- product namely 9 mostly in good yield (see Scheme 5
mer, we decided to use the propargyl allene isomerization and Table 1). As a result of partial hydrodesilylation during
in our investigations.[7,9c,15] The synthetic route to the the reaction of 6d, 6e, and 6n, additional quantities of 9a,
benzo-annulated dipole systems 6a o, prepared as previ- 9b, and 9l had to be added in those cases.
ously reported by us,[13] is shown in Scheme 3.
The nitrone compounds 6, obtained from 1 in crystalline
form with overall yields of 30 50%, were unambiguously
characterized by their analytical data (see Exp. Sect.). In
some cases minor by-products were detected in varying
amounts ( 10%); these turned out to possess the epimino
structure 8 (Scheme 4), formed by rearrangement of the
isoxazolines 7,[16] the direct intramolecular cycloadducts of
6.
Scheme 5
Table 1. Yields of the benzazepinones 9a o from cycloisomeriz-
ation of 6a
o
9[a]
9[a]
a
b
c
d
e
f
84[b]
i
40[b]
77[b]
64[c]
77[b]
93[c]
25[c][g]
76[c]
84[c]
j
85[c]
k
l
m
n
o
24[b][d]
68[c][e]
86[b][f]
46[b] [f]
75[c]
Scheme 4
With the correctly designed nitrones 6 in hand, the tauto-
g
h
merization of the propargyl moiety into the required allenes
was studied next. To our great surprise it turned out that,
on treatment with base even at ambient temperature, the
reaction did not stop at the allene stage but continued dir-
[a]
Reaction conditions: 0.2  in MeOH, 0.5 1.0 equiv. of base,
0.5 5.0 h (f: 24 h; g: 20 h), room temperature. [b] Base: NaOMe.
[d]
[e]
[c] Base: KOH.
29% of 9a.
43% of 9l.
26% of 9b. [f] Solvent:
[g]
ectly to the final products. The experiments were typically CH2Cl2.
3314
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
According to their elemental and MS analyses, the crys-
talline reaction products are isomers of the starting com-
pounds. Their structural identification as 1,2-dihydro[c]-
benzazepin-3-ones 9 was mainly based on spectroscopic in-
1
formation, especially from the H and 13C NMR data. As
demonstrated in the case of 9a, the strong IR absorption at
1
1650 cm and the 13C signal at δ
166.3 indicate the
Figure 2. Minimum geometries of 9a calculated with SPARTAN
1.5 (AM1 method)
1
presence of the lactam carbonyl group, while the H NMR
spectrum shows signals in the aromatic region (4 protons),
the singlet of the N-methyl group (δ
3.11), a singlet for
the methylene protons at C-1 (δ 4.24) and an AB pattern
attributable to the olefinic hydrogen atoms at C-4 and C-5
Table 2. Coalescence temperatures for the ring-inversion of the di-
hydroazepinones 9a, 9b, 9c, 9h, and 9j
(δ
6.41 and 7.08, J
12.2 Hz). The final proof of the
R1
R2
Tc [°C]
simple, but mechanistically quite unexpected, benzazepi-
none structure was provided by crystallographic analysis of
9a (Figure 1).[17]
9a
9b
9h
9c
9j
H
H
C6H5
H
C6H5
CH3
C6H5
CH3
C(CH3)3
C(CH3)3
37
25
10
34
51
plausible initiating reaction (see Scheme 7). Further evid-
ence for the intermediacy of an allene species was obtained
by treatment of the conjugated o-alkynylaryl nitrone 12,
prepared from 10 as shown in Scheme 6, with base. Under
the usual conditions, 12 was transformed into 9h (81% yield
after chromatography and crystallization), the already
known reaction product of 6h (see above); the same allene
tautomer 13h is undoubtedly involved in both cases.
Figure 1. Crystal structure of the benzazepinone 9a (SCHAKAL
drawing, hydrogen atoms omitted; the numbering does not corre-
˚
spond with the correct nomenclature); selected bond lengths [A]
and torsion angels [°]: C1 O 1.234, C1 N 1.342, C1 C2 1.480,
C2 C3 1.330, C3 C4 1.463, C4 C9 1.394, C9 C10 1.497,
C10
C10
N
N
1.462; C1 C2 C3 C4
8.8, N C1 C2 C3 41.2,
C1 C2 4.4, C9 C10
N C1 71.04, C4 C9 C10 N
67.21, C3 C4 C9 C10 3.1, C9 C4 C3 C2 30.7
The boat-shape geometry of the 7-membered ring aside,
there are evidently no particular structural features con-
cerning the bond lengths and angles. The nonplanarity of
the system is also nicely reflected in the 1H NMR spectrum
of the N-tert-butyl derivative 9j, in which the protons at C-
1 appear as an AB system (δ 4.24 and 4.53, J 15.3 Hz),
demonstrating the increasing influence of the bulky sub-
stituent on the ring-flipping process at ambient temper-
ature. On the basis of dynamic NMR measurements, a co-
alescence temperature of 51 °C and a ∆G‡ value of 15.6
kcal/mol (27 °C, CDCl3) were determined for the ring-in-
version process; the two relevant conformations of derivat-
ive 9a are shown in Figure 2. In order to obtain a qualitat-
ive measure of the influence of the particular ring substitu-
ents, the coalescence temperatures of the derivatives a, b, c,
and h were similarly determined. As can be seen in Table 2,
Scheme 6. Reagents: (i) HCϵCCH2Ph, PdCl2(PPh3)2, CuI, NEt3,
C6H6; (ii) CH3NHOH·HCl, NaOAc, CH2Cl2; (iii) NaOMe, MeOH
A
particularly striking feature of the nitrone
groups at C-4 (R1) and the N atom (R2) both contribute to allene benzazepinone transformation concerns the ex-
the decrease in the rate of the inversion process, although change of the terminal and central positions of the allene
to a smaller extent for R2.
group of 13, in which the terminal carbon atom connected
From inspection of the structural differences associated to R1 ends up at C-4, now flanked by both former allene
with the transformation of the starting compounds into the carbon atoms. A possible but still tentative mechanism for
final products, it is obvious that there is no simple connec- this transformation is outlined in Scheme 7 and includes the
tion between the nitrone and azepinone isomers. As far as following steps: (i) 8π-cyclization (13 Ǟ 14),[2,3,5,18] (ii)
the base-free behaviour of the nitrones 6
namely the in- cleavage of the weak NO bond (14 Ǟ 15),[4] (iii) diradical
tramolecular cycloaddition to 7 and its subsequent re- combination (15 Ǟ 16), (iv) one- or two-step cyclization of
arrangement to 8 is concerned, the originally anticipated the azadienylcyclopropanone 16 to 17, and finally (v) a 1,5-
tautomerization to the allenyl derivatives 13 is the most H-shift affording the final products 9.
Eur. J. Org. Chem. 2001, 3313 3332
3315

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
Scheme 8
Scheme 7
Although there is precedent for at least the first two steps
of this sequence, and also the last one, the involvement of
the cyclopropanone 16 is especially intriguing.[19] The
formation of isoindoles 20 as minor side products in a few
cases lends further support to the occurrence of interme-
diates 16 (Scheme 8). Because of the low concentrations and
the chromatographic lability of 20, evidence for the latter is
based only on the 1H NMR and IR spectra. The arylmethyl
derivative 20o, however, could be isolated in 12% yield and
used for a more in-depth spectroscopic and MS/HRMS
analysis. The presence of the carbonyl group is confirmed
Scheme 9
(17p Ǟ 9p).[21] Whereas a few examples have been reported
for 1,5-Cl-migrations,[22] the involvement of Br, to the best
of our knowledge, is otherwise still unknown.
In order to evaluate the structural requirements for the
transformation of type 6 Ǟ 9, an example in which the an-
nulated benzo ring was replaced by a furo ring was investig-
ated. The synthesis of 23 as a representative compound of
this type was accomplished from the protected 3-bromofur-
fural 21, according to the route outlined in Scheme 10. Un-
der basic conditions (NaOMe, MeOH, room temperature),
a clean reaction again took place to afford the furoazepi-
none 24 in almost quantitative yield (91% after crystalliza-
tion). The straightforward formation of 24 is of special im-
portance because, to the best of our knowledge, only deriv-
atives with the carbonyl group next to the furan ring have
so far been described for this heterobicyclic system.
1
by the IR absorption at 1705 cm and the 13C singlet at
1
δ
δ
186.1, while important H resonances are observed at
4.26 (s, 2-H) and 6.89 (s, 3 -H). Together with the other
data, these values are in full agreement with the isoindole
structure 20o (R1 p-tolyl, R2 Me, R3 OMe).[20] Fur-
ther confirmation for this structural assignment was ob-
tained from investigations with some nitrone precursors
that were not benzo-annulated (such as structures 32a and
32b, see below) and from comparison with structurally re-
lated compounds obtained by a different route.[6]
The formation of 20 from 16 can easily be explained by
C C (instead of C CO) cleavage of the cyclopropanone
ring, affording the oxyallyl derivative 18, and subsequent
nucleophilic ring-closure to give the bicyclic dipole 19, fol-
lowed by a proton shift (Scheme 8).
As an additional type of pentenynyl nitrones, the dihy-
dronaphtho derivatives 30a/30b were studied next. The syn-
thetic route followed the same approach as described for
the preparation of 6a o (see Scheme 11): (a) Grignard
coupling (25 Ǟ 26, 88%); (b) hydrodesilylation (26 Ǟ 27,
98%),
(c)
deprotonation methylation deprotection
(27 Ǟ 28 Ǟ 29b, 79%, 84%), (d) deprotection (27 Ǟ 29a,
Concerning the concluding 1,5-H-shift producing 9a o, 99%), (e) nitrone formation (29a,b Ǟ 30a,b, both 62%).
preliminary results with the terminal bromide 6p are inter- To examine the chemical reactivity of the nitrone systems,
esting because the final product 9 p (Scheme 9) contains methanolic solutions were treated with potassium hydroxide
the Br substituent at C-1 and not at C-4; that is, 1,5-Br- (30a) or sodium methoxide (30b) at ambient temperature.
migration (17p Ǟ 9 p) is favoured over an H-shift After workup, product analysis showed that the base-in-
3316
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
ously the concluding 1,5-H shift, favoured by the re-
aromatization process for 17 Ǟ 9 (see Scheme 7), does not
take place for 31a and 31b
the fact that this structure
contains a seemingly unfavourable bis(exo-methylene) ar-
rangement notwithstanding.
In order to rule out any doubt in the structural assign-
ment, a crystallographic analysis of 31a was carried out
(Figure 3).[17] Despite the difference in the arrangement of
the C C bonds, the geometries of the structures of 31a and
9a were quite similar. Again, there are no unusual bond
lengths or angles, and the torsions in the heterocyclic com-
ponents are comparable in both cases (i.e., 30.7° in 9a
and 35.2° in 31a).
Scheme 10. Reagents: (i) a) nBuLi, b) MgBr2, c) BrCH2CϵCSiMe3,
d) PTSA, acetone/H2O; (ii) CH3NHOH·HCl, NaOAc, CH2Cl2; (iii)
NaOAc, MeOH
Figure 3. SCHAKAL plot of the crystal structure of the dihydro-
naphthazepinone 31a (hydrogen atoms omitted; the numbering
does not correspond with the correct nomenclature); selected bond
˚
lengths [A] and torsion angels [°]: C1 O 1.228, C1 N 1.355,
C2 C1 1.507, C2 C3 1.497, C3 C4 1.345, C4 C13 1.464,
C13 C14 1.344, C14
N
1.406;
N
C14 C13 C4
4.1,
N
1.4,
C1
N C14 C13 39.2, C2 C1 N C14 5.5, C3 C2 C1
70.2, C4 C3 C2 C1 68.9, C13 C4 C3 C2
C3 C4 C13 C14 35.2
Separate experiments showed that 31a is indeed the ther-
modynamically more stable bond isomer. Only when it was
heated to ca. 300 °C could the formation of its isomer 33a
1
in very small amounts be detected by H NMR spectro-
scopy (Scheme 12). The equilibrium concentration of 31a/
33a was determined as approximately 15:1. On the other
hand, there was no evidence at all for the 1,5-H-migration
process after 31b had been heated under the same condi-
tions.
Scheme 11. Reagents: (i) a) nBuLi, b) MgBr2, c) BrCH2CϵCSiMe3;
(ii) K2CO3, MeOH; (iii) a) nBuLi, b) CH3I; (iv) PTSA, acetone/
H2O; (v) CH3NHOH·HCl, CH2Cl2; (vi) NaOMe or KOH, MeOH
duced reactions had both resulted in the formation of azepi-
none derivatives 31a or 31b as major products (62%, 64%);
however, the isoindole-type by-products 32a or 32b could
be isolated in much larger quantities (ca. 20% yield after
Scheme 12
Introduction of a phenyl group at the 4-position of the
purification) than in the case of the nitrones 6 (see above). tricyclic system should be expected to produce a change in
Clear structural characterization could be achieved for both the equilibrium in favour of the endocyclic tautomer. For
1
systems on the basis of their IR, H/13C NMR and MS/ the synthesis of appropriate precursors, the α-tetralones 34a
HRMS data.
and 34b (n
1) and the benzosuberone 34c (n
2) were
Surprisingly, the arrangement of the C C bonds in the used as starting materials. Transformation into 37a, 37b,
dihydroazepinones 31a and 31b (‘‘dienamine’’-type) differs and 37c was accomplished by a straightforward sequence
from that in the analogues 9a o (‘‘dienone’’-type). Obvi- of (i) Vilsmeier bromoformylation, (ii) Sonogashira coup-
Eur. J. Org. Chem. 2001, 3313 3332
3317

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
ling, and (iii) nitrone formation (Scheme 13). In analogy to ive 9d, bromodesilylation was achieved by treatment with
compound 12, but in contrast to all the other nitrone sys- Br2, producing the vinyl bromide 9p (79%).[25]
tem used in this work, 37a, 37b, and 37c contain conjugated
propargyl groups, which means that the reactive allene unit
is formed by formal shift of an ‘‘outer’’ proton.
Scheme 14
Conclusion
Despite the structural simplicity of the 1,2-dihydro[c]-
benzazepin-3-one system 9, which has been found as a sub-
structure in several naturally occurring compounds,[26] no
general synthetic procedures for it are available. Only a few
syntheses have so far been described, these mostly having
been elaborated for the preparation of further annulated
compounds, which frequently possess biological activity.[27]
The parent compound of 9 (9a, R2
H) has been synthe-
sized in modest yield by irradiation of β-azidonaphthalene
in methanol and subsequent hydrolysis of the iminoether.[28]
The novel reaction principle described in this paper is a very
useful and broadly applicable route to this class of com-
pounds, and can easily be performed under extraordinarily
mild conditions, with respect both to the base and to the
reaction temperature; in many cases the reaction takes place
even at 0 °C. The ease of the rearrangement and the high
product yields are particularly surprising in view of the
complexity of the overall reaction sequence. It should be
mentioned that the transformation is quite general and not
restricted to the preparation of annulated dihydroazepi-
nones, being similarly applicable for monocyclic systems.[29]
Scheme 13. Reagents: (i) PBr3, DMF, CHCl3; (ii) HCϵCCH2Ph,
PdCl2(PPh3)2, CuI, K2CO3 and/or NEt3, C6H6; (iii)
CH3NHOH·HCl, NaOAc, CH2Cl2; (iv) NaOMe or KOH, MeOH
After treatment of 37a, 37b, and 37c with base (NaOMe
or KOH in MeOH) at 20 °C, single monomeric products
were detected in each case. These were the exo-methylene-
type annulated azepinones 38a (78%), 38b (90%), and 38c
(67%; all yields after chromatography and crystallization),
respectively. On their being heated in boiling toluene, how-
ever, tautomerization into the endocyclic compounds 39
took place, reaching equilibrium ratios of 3:2 (a, b) and 4:1
(c), although still in favour of the former isomer 38.
Reactivity of Some Dihydrobenzazepin-3-ones
Experimental Section
The kinetic stability, both thermal and chemical, of the
heterocycles is unusually high. For instance, no cleavage of
the amide bond could be detected even under forced acidic
or basic conditions. The chemical reactivity of the benza-
zepinone system was investigated with several representative
examples. Reduction of either the C C or the C O groups
of 9a and 9c, for instance, can be achieved chemoselectively,
depending on the reducing agent. Whereas catalytic hydro-
genation afforded the tetrahydrobenzazepinones 41, treat-
ment with lithium aluminium hydride resulted in the forma-
tion of the respective dihydroazepines 40 (Scheme 14). A
further group transformation was effected by treatment of
9a with P4S10,[23] which afforded the thioketone 42. Al-
though the use of Lawesson’s reagent has also been de-
scribed for similar applications,[24] this was much less effici-
General: Melting points are uncorrected. IR: Perkin Elmer 257
Infracord.
(400 MHz), and DRX 500 (500 MHz).
1H NMR: Bruker WM 250 (250 MHz), WM 400
13C NMR: Bruker WM
400 (100 MHz) and DRX 500 (125 MHz); CDCl3 as solvent and
TMS as internal standard. MS: Finnigan MAT 44 S (70 eV) with
Datasystem MAT SS 200.
Elemental Analyzer 240. Products were isolated by flash chroma-
tography on silica gel (Silica 32 36, ICN Biomedicals).
SiO2 60 F-254, 0.2 mm (Merck).
Elemental analyses: Perkin Elmer
TLC:
General Procedure for the Cleavage of 1,3-Dioxolanes: A 0.15 
solution of the dioxolane in a 1.2:1 mixture of acetone and water
was treated with 5 mol % of PTSA and refluxed until completion
of the reaction (TLC, 1 6 h). After this had cooled to room temp.,
satd. aqueous NaHCO3 was added and the solution was extracted
ent in our example. In the case of the trimethylsilyl derivat- with diethyl ether. The combined organic phases were washed with
3318 Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
brine, dried (MgSO4), and concentrated in vacuo. The residue was organic phases were washed with brine, dried (MgSO4), and con-
FULL PAPER
purified by flash chromatography (SiO2).
centrated in vacuo. Flash chromatography (SiO2, cyclohexane/ethyl
acetate 60:1) afforded 3l (8.05 g, 72%) as pale yellow crystals.
General Procedure for the Preparation of N-Methyl-Substituted
Nitrones: Sodium acetate (3 equiv.) was added to a 0.25  suspen-
sion of N-methylhydroxylamine hydrochloride (1.3 equiv.) in dry
CH2Cl2, followed after stirring for 15 min by the corresponding
aldehyde (1 equiv.). The reaction mixture was stirred at room temp.
until completion of the reaction (TLC), hydrolysed with water and
extracted with CH2Cl2. The combined organic phases were washed
with brine, dried (MgSO4), and concentrated in vacuo. The crude
material was purified by flash chromatography (SiO2).
M.p. 67 70 °C (diethyl ether).
IR (CCl4): ν˜
3315 (ϵC H),
2995, 2955, 2880, 2115 (CϵC), 1610, 1515, 1465, 1300, 1275, 1225,
1
1120, 1075, 1010 cm
.
1H NMR (250 MHz): δ
2.20 (t,
4J3 2.7 Hz, 1 H, 3 -H), 3.71 (d, 4J1
2.7 Hz, 2 H, 1 -H),
,1
,3
3.89 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3), 4.09 (mc, 4 H, 4-H, 5-
H), 5.92 (s, 1 H, 2-H), 7.09 (s, 1 H, Ar-H), 7.10 (s, 1 H, Ar-H).
13C NMR (100 MHz): δ 21.3 (C-1 ), 56.1 (OCH3), 56.2 (OCH3),
65.2 (C-4, C-5), 70.7 (C-3 ), 82.0 (C-2 ), 101.6 (C-2), 109.9 (C-3 /
6 ), 112.5 (C-3 /6 ), 126.8 (C-1 /2 ), 127.3 (C-1 /2 ), 147.7 (C-4 /5 ),
149 6 (C-4 /5 ). MS (70 eV; EI): m/z (%) 248 (83) [M ], 204
General Procedure for the Preparation of N-Phenyl-Substituted
Nitrones: A 0.2  solution of the corresponding aldehyde in dry
CH2Cl2 was treated with N-phenylhydroxylamine (1.1 equiv.) and
stirred in the dark for 6 45 h. The mixture was treated with water
and extracted with CH2Cl2. The combined organic phases were
washed with brine, dried (MgSO4), and concentrated in vacuo. The
crude material was purified by flash chromatography (SiO2).
(100), 188 (62), 176 (68), 161 (60), 73 (74).
calcd. C 67.52, H 6.50; found C 67.52, H 6.39.
C14H16O4 (248.28):
2-[2 -(But-2 -ynyl)phenyl]-1,3-dioxolane (4f): A solution of n-butyl-
lithium in n-hexane (2.4 , 9.8 mL, 23.5 mmol) was added dropwise
at 78 °C under N2 to a solution of 3a[33] (4.00 g, 21.4 mmol) in
100 mL of dry THF. The mixture was stirred for 2 h and methyl
iodide (3.33 g, 23.5 mmol) was added at 78 °C. The solution was
allowed to warm to room temp. and stirred for a further 70 h. A
1:1 mixture of satd. NH4Cl and water was added and the reaction
General Procedure for the Base-Catalysed Transformations of the
Nitrones: A 0.2  solution of the corresponding nitrone in dry
methanol was treated with base (0.5 equiv.) and stirred at room
temp. until completion of the reaction (TLC). The mixture was
hydrolysed with water and extracted with CH2Cl2. The combined
organic phases were washed with satd. aqueous NH4Cl and with
brine, dried (MgSO4), and concentrated in vacuo. The residue was
purified by flash chromatography (SiO2).
mixture was extracted with diethyl ether (3
40 mL). The com-
bined organic phases were washed with brine, dried (MgSO4), and
concentrated in vacuo. Flash chromatography (SiO2; cyclohexane/
ethyl acetate, 50:1) afforded 4f (3.14 g, 73%) as a pale yellow oil.
˜
IR (CCl4): ν 2950, 2920, 2885, 1480, 1450, 1390, 1220, 1110,
1
5
1075 cm
.
1H NMR (250 MHz): δ
1.85 (t, J4
2.6 Hz,
,1
{3-[2 -(1 ,3 -Dioxolan-2 -yl)-4 ,5 -dimethoxyphenyl]prop-1-ynyl}-
trimethylsilane (2n): A solution of n-butyllithium in n-hexane (2.4
, 6.34 mL, 16.6 mmol) was added dropwise to a solution of 2-(2 -
5
3 H, 4 -H), 3.71 (q, J1
2.6 Hz, 2 H, 1 -H), 4.08 (mc, 4 H,
,4
4-H, 5-H), 6.02 (s, 1 H, 2-H), 7.21 7.41 (m, 2 H, Ar-H), 7.55 (mc,
2 H, Ar-H). 13C NMR (100 MHz): δ 3.6 (C-4 ), 22.1 (C-1 ),
65.2 (C-4, C-5), 76.4 (C-2 /3 ), 78.3 (C-2 /3 ), 101.9 (C-2), 126.1
(Ar-C), 126.6 (Ar-C), 129.1 (Ar-C), 129.3 (Ar-C), 134.8 (Ar-Cq),
bromo-4 ,5 -dimethoxyphenyl)-1,3-dioxolane[30]
(4.00 g,
13.8
mmol) in dry THF (120 mL) at 78 °C under N2. After this had
stirred for 2 h at 78 °C, a solution of MgBr2 in diethyl ether (10
mL), freshly prepared from Mg (480 mg, 19.8 mmol) and dibromo-
ethane (2.86 g, 15.2 mmol),[31] was added slowly and the reaction
mixture was allowed to warm to room temp. After 2 h, 1-bromo-
3-(trimethylsilyl)prop-2-yne[32] (3.17 g, 16.6 mmol) was added and
the solution was refluxed for 2 h. After cooling to room temp., the
solution was treated with a 1:1 mixture of satd. NH4Cl and water
136.1 (Ar-Cq).
MS (70 eV; EI): m/z (%)
201 (12) [M
1],
187 (44), 141 (47), 129 (98), 105 (93).
1]: calcd. 201.0916; found 201.0917.
HRMS (C13H14O2) [M
2-[2 -(3 -Phenylprop-2 -ynyl)phenyl]-1,3-dioxolane (4n): Freshly
distilled iodobenzene (0.36 mL, 3.20 mmol), PdCl2(PPh3)2 (94 mg,
0.13 mmol) and CuI (ca. 10 mg) were added to a solution of 3a[33]
(500 mg, 2.67 mmol) in dry and degassed (Ar) triethylamine (10
mL). After stirring under argon for 5 h at room temp., the mixture
was filtered and the solution was concentrated in vacuo. The brown
residue was purified by flash chromatography (SiO2; cyclohexane/
ethyl acetate, 40:1) to afford 4n (580 mg, 82%) as a yellow oil.
and extracted with diethyl ether (3
60 mL). The combined or-
ganic phases were washed with brine, dried (MgSO4), and concen-
trated in vacuo. Flash chromatography (SiO2; cyclohexane/ethyl
acetate, 20:1, 10:1) afforded 2n (2.85 g, 64%) as pale yellow oil,
which crystallized from diethyl ether.
ether). IR (CCl4): ν˜ 2960, 2890, 2175 (CϵC), 1520, 1465,
1400, 1295, 1270, 1200, 1120, 1005 cm
0.19 (s, 9 H, SiMe3), 3.57 (s, 2 H, 3-H), 3.70 (s, 3 H, OCH3),
3.72 (s, 3 H, OCH3), 3.89 (mc, 4 H, 4 -H, 5 -H), 5.89 (s, 1 H, 2 -
H), 7.08 (s, 1 H, Ar-H), 7.16 (s, 1 H, Ar-H).
13C NMR
(100 MHz): δ 0.1 (SiMe3), 22.6 (C-3), 55.8 (OCH3), 56.0
M.p. 60 62 °C (diethyl
˜
IR (CCl4): ν
1115, 1075, 1030 cm
1 -H), 4.01 4.20 (m, 4 H, 4-H, 5-H), 6.10 (s, 1 H, 2-H), 7.22 7.50
(m, 7 H, Ar-H), 7.52 7.70 (m, 2 H, Ar-H).
13C NMR
3065, 2950, 2885, 1595, 1490, 1455, 1390, 1220,
1
1H NMR (250 MHz): δ 4.00 (s, 2 H,
1
.
1H NMR (250 MHz):
.
δ
(125 MHz): δ 22.8 (C-1 ), 65.3 (C-4, C-5), 83.2 (C-2 /3 ), 87.3
(C-2 /3 ), 102.1 (C-2), 123.4 (Ar-Cq), 126.4 (Ar-C), 126.8 (Ar-C),
127.9 (Ar-C), 128.3 (Ar-C), 129.2 (Ar-C), 129.5 (Ar-C), 131.7 (Ar-
C), 134.9 (Ar-Cq), 134.9 (Ar-Cq). MS (70 eV; EI): m/z (%) 264
(12) [M ], 203 (47), 192 (100) [PhCH2CϵCPh ], 105 (92).
HRMS (C18H16O2): calcd. 264.1150; found 264.1151.
(OCH3), 87.6 (C-2), 101.6 (C-2 ), 104.5 (C-1), 109.7 (C-3 /6 ),
112.3 (C-3 /6 ), 126.7 (C-1 /2 ), 127.5 (C-1 /2 ), 147.5 (C-4 /5 ),
149.4 (C-4 /5 ).
MS (70 eV; EI): m/z (%)
320 (16) [M ], 261
(24), 247 (13) [M
Si(CH3)3] , 233 (26), 222 (26), 73 (100)
[Si(CH3)3 ]. C17H24O4Si (320.46): calcd. C 63.72, H 7.55; found
C 63.41, H 7.51.
2-{2 -[3 -(4 -Methylphenyl)prop-2 -ynyl]phenyl}-1,3-dioxolane
(4k): A solution of 3a[33] (1.00 g, 5.34 mmol) and 4-iodotoluene
(1.40 g, 6.41 mmol) in dry Et3N (20 mL) was degassed (Ar) and
treated with PdCl2(PPh3)2 (187 mg, 0.27 mmol) and CuI (ca.
2-[4 ,5 -Dimethoxy-2 -(prop-2 -ynyl)phenyl]-1,3-dioxolane (3l):
A
solution of 2n (14.4 g, 44.9 mmol) in CH2Cl2 (180 mL) was treated
with Bu4NHSO4 (7.64 g, 22.5 mmol), KF (13.1 g, 22.5 mmol), and 15 mg). After stirring under argon for 4 h at room temp., the reac-
NH4Cl (14.4 g, 270 mmol), and the resulting mixture was then tion mixture was filtered and the solution was concentrated in va-
stirred for 18 h at room temp. Water (80 mL) was added and the cuo. Purification of the brown residue by flash chromatography
solution was extracted with CH2Cl2 (3
30 mL). The combined
(SiO2; cyclohexane/ethyl acetate, 40:1) afforded 4k (1.00 g, 67%) as
Eur. J. Org. Chem. 2001, 3313 3332
3319

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
5
a yellow oil. IR (CCl4): ν˜ 3030, 2950, 2885, 1510, 1455, 1395,
1H NMR (250 MHz): δ
1.89 (t, J4 ,1
2.6 Hz, 3 H, 4 -H),
1
5
1220, 1115, 1075 cm
.
1H NMR (250 MHz): δ 2.34 (s, 3 H, 4.00 (q, J1 ,4
2.6 Hz, 2 H, 1 -H), 7.44 (mc, 1 H, Ar-H), 7.58
Ar-CH3), 3.99 (s, 2 H, 1 -H), 4.10 (mc, 4 H, 4-H, 5-H), 6.06 (s, 1 (mc, 1 H, Ar-H), 7.69 (mc 1 H, Ar-H), 7.81 (mc, 1 H, Ar-H), 10.26
H, 2-H), 7.10 (mc, 2 H, Ar-H), 7.27 7.41 (m, 4 H, Ar-H), 7.56 (s, 1 H, CHO). 3.6 (C-4 ), 22.9 (C-
13C NMR (100 MHz): δ
(mc, 1 H, Ar-H), 7.64 (mc, 1 H, Ar-H). MS (70 eV; EI): m/z 1 ), 76.1 (C-2 /3 ), 79.3 (C-2 /3 ), 127.2 (Ar-C), 130.0 (Ar-C), 132.9
(%) 278 (1) [M ], 149 (36), 115 (90), 105 (68), 91 (46) [CH2Ph ], (Ar-C), 133.3 (Ar-Cq), 134.0 (Ar-C), 139.8 (Ar-Cq), 192.7 (CHO).
77 (52). HRMS (C19H18O2): calcd. 278.1307; found 278.1308.
MS (70 eV; EI): m/z (%)
158 (100) [M ], 129 (82) [M
CHO] , 128 (76), 115 (74). HRMS (C11H10O): calcd. 158.0732;
found 158.0731.
2-{4 ,5 -Dimethoxy-2 -[3 -(4 -methylphenyl)prop-2 -ynyl]phenyl}-
1,3-dioxolane (4o): A solution of 3l (2.59 g, 7.65 mmol) in benzene
(20 mL) was treated with dry Et3N and degassed (Ar). 4-Iodotol-
2-(3 -Phenylprop-2 -ynyl)benzaldehyde (5h): Treatment of 4h
uene (2.00 g, 9.18 mmol), PdCl2(PPh3)2 (268 mg, 0.38 mmol), and (560 mg, 2.12 mmol, 4 h) according to the general procedure, after
CuI (ca. 10 mg) were added, and the solution was stirred under Ar
for 50 h at room temp. The reaction mixture was filtered and the
solution was concentrated in vacuo. Purification of the brown res-
idue by flash chromatography (SiO2; cyclohexane/ethyl acetate, 5:1,
purification (cyclohexane/ethyl acetate, 40:1), gave 5h (339 mg,
˜
72%) as a dark yellow oil. IR (CCl4): ν 3060, 2815, 2730, 1700
1
(C O), 1600, 1575, 1490, 1440, 1325, 1285, 1215, 1145, 1075 cm
.
1H NMR (250 MHz): δ
4.20 (s, 2 H, 1 -H), 7.22 7.35 (m, 3
2:1) afforded 4o (1.62 g, 63%) as pale yellow crystals, m.p. 99 100 H, Ar-H), 7.40 7.51 (m, 3 H, Ar-H), 7.61 (mc, 1 H, Ar-H), 7.82
13C NMR (125 MHz):
˜
°C (diethyl ether). IR (CCl4): ν 2955, 2880, 1510, 1465, 1400,
(mc, 2 H, Ar-H), 10.29 (s, 1 H, CHO).
23.6 (C-1 ), 84.0 (C-2 /3 ), 86.8 (C-2 /3 ), 123.5 (Ar-Cq), 127.4
2.34 (s, 3 H, CH3), 3.90 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3), (Ar-C), 128.0 (Ar-C), 128.3 (Ar-C), 130.0 (Ar-C), 131.7 (Ar-C),
1
1275, 1205, 1180, 1120, 1070, 1010 cm
.
1H NMR (250 MHz):
δ
δ
4.11 (mc, 4 H, 4-H, 5-H), 5.99 (s, 1 H, 2-H), 7.10 (mc, 2 H, Ar-H), 133.4 (Ar-Cq), 133.6 (Ar-C), 134.1 (Ar-C), 138.8 (Ar-Cq), 192.8
7.12 (s, 1 H, 3 /6 -H), 7.16 (s, 1 H, 3 /6 -H), 7.33 (mc, 2 H, Ar-H). (CHO). MS (70 eV; EI): m/z (%) 220 (81) [M ], 191 (100) [M
13C NMR (100 MHz): δ
21.5 (CH3), 22.3 (C-1 ), 56.0
CHO] , 189 (67), 165 (59), 118 (69). HRMS (C16H12O): calcd.
(OCH3), 56.1 (OCH3), 65.2 (C-4, C-5), 83.1 (C-2 /3 ), 86.8 (C-2 / 220.0889; found 220.0888.
3 ), 101.6 (C-2), 109.7 (Ar-C), 112.6 (Ar-C), 120.7 (Ar-Cq), 126.9
2-[3 -(4 -Methylphenyl)prop-2 -ynyl]benzaldehyde (5k): Treatment
of 4k (887 mg, 3.19 mmol, 2 h) according to the general procedure,
after purification (cyclohexane/ethyl acetate, 40:1), gave 5k
(Ar-Cq), 128.1 (Ar-Cq), 129.1 (Ar-C), 131.5 (Ar-C), 137.9 (Ar-Cq),
147.6 (Ar-Cq), 149.5 (Ar-Cq). MS (70 eV; EI): m/z (%) 338 (1)
[M ], 136 (71), 119 (64), 92 (20), 91 (100).
calcd. 338.1518; found 338.1518.
HRMS (C21H22O4):
˜
(618 mg, 83%) as a yellow oil. IR (CCl4): ν 3025, 2920, 2825,
1
2735, 1700 (C O), 1600, 1510, 1325, 1195 cm
(250 MHz): δ 2.34 (s, 3 H, CH3), 4.28 (s, 2 H, 1 -H), 7.11 (mc,
2 H, Ar-H), 7.34 (mc, 2 H, Ar-H), 7.46 (mc, 1 H, Ar-H), 7.60 (mc,
13C
.
1H NMR
2-(Prop-2 -ynyl)benzaldehyde (5a): Treatment of 3a[33] (4.00 g,
21.4 mmol, 6 h) according to the general procedure, after purifica-
tion (cyclohexane/ethyl acetate, 40:1), gave 5a (2.87 g, 93%) as a 1 H, Ar-H), 7.82 (mc, 2 H, Ar-H), 10.27 (s, 1 H, CHO).
pale yellow oil. IR (CCl4): ν˜ 3315 (ϵC H), 2825, 2730, 2120 NMR (100 MHz): δ 21.5 (CH3), 23.6 (C-1 ), 84.1 (C-2 /3 ), 86.0
(CϵC), 1700 (C O), 1600, 1575, 1490, 1450, 1325, 1295, 1195 (C-2 /3 ), 120.4 (Ar-Cq), 127.3 (Ar-C), 129.1 (Ar-C), 130.0 (Ar-C),
1
4
cm
.
1H NMR (250 MHz): δ
2.27 (t, J3 ,1
2.7 Hz, 1 H, 131.6 (Ar-C), 133.4 (Ar-Cq), 133.5 (Ar-C), 134.1 (Ar-C), 138.1 (Ar-
4
3 -H), 4.10 (d, J1 ,3
2.7 Hz, 2 H, 1 -H), 7.49 (mc, 1 H, Ar-H), Cq), 139.0 (Ar-Cq), 192.7 (CHO). MS (70 eV; EI): m/z (%)
7.60 (mc, 1 H, Ar-H), 7.65 (mc, 1 H, Ar-H), 7.72 (mc, 1 H, Ar-H), 234 (83) [M ], 219 (48), 205 (53) [M CHO] , 191 (100), 118 (48).
10.21 (s, 1 H, CHO).
71.8 (C-3 ), 81.2 (C-2 ), 127.4 (Ar-C), 129.9 (Ar-C), 133.2 (Ar-Cq),
133.9 (Ar-C), 134.0 (Ar-C), 137.0 (Ar-Cq), 192.8 (CHO). MS
(70 eV; EI): m/z (%) 144 (39) [M ], 128 (9), 116 (48), 115 (100)
[M CHO] . HRMS (C10H8O): calcd. 144.0575; found
144.0576.
13C NMR (125 MHz): δ
22.6 (C-1 ),
HRMS (C17H14O): calcd. 234.1045; found 234.1044.
4,5-Dimethoxy-2-(prop-2 -ynyl)benzaldehyde (5l): Treatment of 4l
(2.00 g, 8.05 mmol, 6 h) according to the general procedure, after
purification (cyclohexane/ethyl acetate, 30:1, 10:1), gave 5l (1.34 g,
82%) as colourless crystals, m.p. 103 104 °C (diethyl ether). IR
˜
(CCl4): ν
3310 (ϵC H), 3000, 2935, 2845, 2715, 2120 (CϵC),
1
2-[3 -(Trimethylsilyl)prop-2 -ynyl]benzaldehyde (5d): Treatment of
2d[33] (6.00 g, 23.0 mmol, 4 h) according to the general procedure,
after purification (cyclohexane/ethyl acetate, 20:1), gave 5d (4.75 g,
1695 (C O), 1600, 1570, 1520, 1465, 1280, 1230, 1180, 1110 cm
.
1H NMR (250 MHz): δ
3.94 (s, 3 H, OCH3), 4.00 (s, 3 H, OCH3), 4.03 (md, 4J1 ,3
2 H, 1 -H), 7.16 (s, 1 H, Ar-H), 7.34 (s, 1 H, Ar-H), 10.16 (s, 1 H,
(CϵC), 1700 (C O), 1600, 1575, 1490, 1455, 1400, 1320, 1290, CHO). 21.8 (C-1 ), 56.2 (OCH3),
13C NMR (100 MHz): δ
0.17 [s, 9 H, 71.8 (C-3 ), 81.4 (C-2 ), 112.4 (C-3/6), 113.8 (C-3/6), 126.2 (C-1/2),
Si(CH3)3], 4.09 (s, 2 H, 1 -H), 7.43 (mc, 1 H, 4/5-H), 7.57 (mc, 1 H, 133.1 (C-1/2), 148.1 (C-4/5), 153.8 (C-4/5), 190.2 (CHO). MS
4/5-H), 7.71 (mc, 1 H, 3/6-H), 7.79 (mc, 1 H, 3/6-H), 10.37 (s, 1 H, (70 eV; EI): m/z (%) 204 (100) [M ], 189 (51), 161 (64), 133
CHO). 0.1 [Si(CH3)3], 24.0 (C-1 ), (51), 118 (35), 105 (28). HRMS (C12H12O3): calcd. 204.0786;
13C NMR (100 MHz): δ
2.28 (t, J3 ,1
2.7 Hz, 1 H, 3 -H),
2.7 Hz,
4
95%) as a pale yellow oil.
IR (CCl4): ν˜
2960, 2735, 2180
1
1200, 1030 cm
.
1H NMR (250 MHz): δ
88.6 (C-3 ), 103.5 (C-2 ), 127.3 (Ar-C), 129.9 (Ar-C), 133.3 (Ar- found 204.0786.
Cq), 133.4 (Ar-C), 134.1 (Ar-C), 138.5 (Ar-Cq), 192.7 (C O).
4,5-Dimethoxy-2-[3 -(trimethylsilyl)prop-2 -ynyl]benzaldehyde (5n):
Treatment of 2n (1.94 g, 6.06 mmol, 2 h) according to the general
procedure, after purification (cyclohexane/ethyl acetate, 30:1. 10:1),
gave 5n (1.41 g, 84%) as colourless crystals, m.p. 88 90 °C (diethyl
ether). IR (CCl4): ν˜ 3000, 2960, 2835, 2175 (CϵC), 1695 (C
MS (70 eV; EI): m/z (%)
(21), 73 (100) [Si(CH3)3 ]. HRMS (C13H16OSi): calcd. 216.0970;
found 216.0969.
216 (42) [M ], 201 (86), 186 (16), 141
2-(But-2 -ynyl)benzaldehyde (5f): Treatment of 4f (2.00 g,
9.94 mmol, 2 h) according to the general procedure, after purifica-
tion (cyclohexane/ethyl acetate, 50:1), gave 5f (1.42 g, 91%) as a cm
O), 1600, 1570, 1520, 1465, 1350, 1280, 1230, 1175, 1100, 1000
1
.
1H NMR (400 MHz): δ 0.19 (s, 9 H, SiMe3), 3.94 (s, 3
colourless oil that rapidly turned yellow.
2855, 2735, 1700 (C O), 1600, 1575, 1450, 1325, 1295, 1195 cm
IR (CCl4): ν˜
2920,
H, OCH3), 3.99 (s, 3 H, OCH3), 4.06 (s, 2 H, 1 -H), 7.22 (s, 1 H,
Ar-H), 7.33 (s, 1 H, Ar-H), 10.16 (s, 1 H, CHO).
1
.
13C NMR
3320
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
(100 MHz): δ 0.1 (SiMe3), 23.1 (C-1 ), 56.1 (OCH3), 56.2 afforded 6c (141 mg, 95%) as colourless crystals, m.p. 36 37 °C
FULL PAPER
˜
(OCH3), 88.7 (C-2 ), 103.7 (C-3 ), 112.3 (C-3/6), 113.5 (C-3/6), (ethanol). IR (CCl4): ν 3310 (ϵC H), 3065, 2975, 2935, 1555,
1
126.2 (C-1/2), 133.5 (C-1/2), 148.0 (C-4/5), 153.7 (C-4/5), 190.2 1470, 1430, 1360, 1195, 1135 cm
.
1H NMR (250 MHz): δ
4
(CHO). MS (70 eV; EI): m/z (%) 276 (32) [M] , 261 (23), 231
(25), 203 (10) [M Si(CH3)3] , 73 (100) [Si(CH3)3 ].
1.64 (s, 9 H, CH3), 2.21 (t, J3
2.7 Hz, 1 H, 3 -H), 3.63 (d,
,1
HRMS 4J1
2.7 Hz, 2 H, 1 -H), 7.31 7.39 (m, 3 H, Ar-H), 7.94 (s, 1
,3
(C15H20O3Si): calcd. 276.1182; found 276.1181.
H, 1-H), 9.01 9.07 (m, 1 H, 6 -H). 13C NMR (125 MHz): δ
23.6 (C-1 ), 28.3 (CH3), 71.2 (C-3 ), 71.5 (Cq), 81.3 (C-2 ), 126.6
(Ar-Cq), 127.5 (Ar-C), 128.4 (Ar-C), 129.1 (Ar-C), 129.9 (Ar-C),
4,5-Dimethoxy-2-[3 -(4 -methylphenyl)prop-2 -ynyl]benzaldehyde
(5o): Treatment of 4o (784 mg, 2.32 mmol, 3 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
20:1), gave 5o (559 mg, 82%) as colourless crystals, m.p. 92 93 °C
134.6 (Ar-Cq).
MS (70 eV; EI): m/z (%)
(19), 142 (29), 128 (24), 57 (100) [C(CH3)3 ].
(C14H17NO): calcd. 215.1310; found 215.1309.
215 (16) [M ], 159
HRMS
˜
(diethyl ether). IR (CCl4): ν 3005, 2955, 2840, 2710, 1690 (C
1
O), 1600, 1570, 1515, 1465, 1280, 1230, 1175, 1105 cm
.
1H
Methyl{[2 -(3 -trimethylsilylprop-2 -ynyl)phenyl]methylene}amine
NMR (250 MHz): δ 2.34 (s, 3 H, CH3), 3.95 (s, 3 H, OCH3), N-Oxide (6d): Treatment of 5d (1.20 g, 5.55 mmol, 5 h) according
3.99 (s, 3 H, OCH3), 4.22 (s, 2 H, 1 -H), 7.11 (mc, 2 H, Ar-H), 7.21 to the general procedure, after purification (cyclohexane/ethyl acet-
(s, 1 H, 3/6-H), 7.22 (mc, 2 H, Ar-H), 7.37 (s, 1 H, 3/6-H), 10.25 ate, 3:1, 1:2), gave 6d (904 mg, 66%) as a colourless solid, m.p.
(s, 1 H, CHO). 13C NMR (100 MHz): δ 21.5 (CH3), 22.7 (C-
67 68 °C (ethanol, decomp.).
(CϵC), 1715, 1580, 1560, 1450, 1420, 1250, 1190, 1015 cm
0.17 (s, 9 H, SiMe3), 3.66 (s, 2 H, 1 -
134.2 (C-1/2), 138.2 C-1/2), 148.1 (C-4/5), 153.8 (C-4/5), 190.2 H), 3.93 (s, 3 H, NCH3), 7.32 7.51 (m, 3 H, Ar-H), 7.72 (s, 1 H,
(CHO). MS (70 eV; EI): m/z (%) 294 (100) [M ], 279 (16), 1-H), 9.03 (mc, 1 H, 6 -H). 0.0
13C NMR (100 MHz): δ
IR (CCl4): ν
2935, 2855, 2175
˜
1
1 ), 56.2 (OCH3), 84.1 (C-2 /3 ), 86.2 (C-2 /3 ), 112.5 (Ar-C), 113.2
.
(Ar-C), 120.3 (Ar-C), 126.4 (Ar-C), 129.1 (C-3/6), 131.5 (C-3/6), 1H NMR (400 MHz): δ
194 (39), 178 (36), 165 (61).
H 6.16; found C 77.52, H 6.06.
C19H18O3 (294.35): calcd. C 77.53, (SiMe3), 24.9 (C-1 ), 55.0 (NCH3), 88.1 (C-3 ), 103.3 (C-2 ),
127.4 (Ar-C), 128.3 (Ar-C), 128.6 (Ar-Cq), 129.2 (Ar-C), 130.3 (Ar-
C), 131.8 (C-1), 134.5 (Ar-Cq).
(10) [M ], 230 (36), 172 (19) [M
MS (70 eV; EI): m/z (%)
Si(CH3)3] , 144 (34), 73 (100)
245
Methyl{[2 -(prop-2 -ynyl)phenyl]methylene}amine N-Oxide (6a):
Treatment of 5a (2.31 g, 16.0 mmol, 2 h) according to the general
procedure, after purification (cyclohexane/ethyl acetate, 3:1, 1:2),
gave 6a (2.40 g, 86%) as colourless crystals, m.p. 100 101 °C (di-
[Si(CH3)3 ].
C14H19NOSi (245.40): calcd. C 68.52, H 7.80, N
5.71; found C 68.49, H 7.82, N 5.64.
˜
ethyl ether, decomp.). IR (CCl4): ν 3310 (ϵC H), 3065, 3020, N-({2 -[3 -(Trimethylsilyl)prop-2 -ynyl]phenyl}methylene)aniline
1
2049, 2115 (CϵC), 1580, 1560, 1425, 1190, 1175 cm
(250 MHz): δ 2.8 Hz, 1 H, 3 -H), 3.62 (d, to the general procedure, after purification (cyclohexane/ethyl acet-
2.25 (t, 4J3
4J1
2.8 Hz, 2 H, 1 -H), 3.92 (s, 3 H, NCH3), 7.30 7.48 (m, ate, 10:1), gave 6e (796 mg, 58%) as colourless crystals, m.p. 96 97
.
1H NMR
N-Oxide (6e): Treatment of 5d (1.00 g, 4.62 mmol, 6 h) according
,1
,3
3 H, Ar-H), 7.68 (s, 1 H, 1-H), 9.02 (mc, 1 H, 6 -H). 13C NMR °C (diethyl ether, decomp.).
IR (CCl4): ν
3065, 2960, 2895,
˜
1
(100 MHz): δ
23.4 (C-1 ), 55.0 (NCH3), 71.6 (C-3 ), 81.1 (C- 2175 (CϵC), 1590, 1545, 1490, 1460, 1250, 1205, 1015 cm
.
1H
2 ), 127.5 (Ar-C), 128.4 (Ar-C), 128.5 (Ar-Cq), 129.1 (Ar-C), 130.4 NMR (250 MHz): δ
0.15 (s, 9 H, SiMe3), 3.73 (s, 2 H, 1 -H),
(Ar-C), 131.7 (C-1), 134.2 (Ar-Cq).
173 (23) [M ], 134 (27), 128 (100) [M
MS (70 eV; EI): m/z (%)
NOCH3] , 115 (21), 77 H, 1-H), 9.38 (mc, 1 H, 6 -H).
7.35 7.56 (m, 6 H, Ar-H), 7.78 7.90 (m, 2 H, Ar-H), 8.38 (s, 1
13C NMR (100 MHz): δ
0.2
(25). HRMS (C11H11NO): calcd. 173.0841; found 173.0843.
(SiMe3), 25.2 (C-1 ), 88.1 (C-3 ), 103.5 (C-2 ), 121.9 (Ar-C),
127.7 (Ar-C), 128.6 (Ar-C), 128.9 (Ar-Cq), 129.2 (Ar-C), 129.6 (Ar-
C), 130.9 (Ar-C), 131.5 (C-1), 135.4 (Ar-Cq), 149.7 (Ar-Cq). MS
N-{[2 -(Prop-2 -ynyl)phenyl]methylene}aniline N-Oxide (6b): Treat-
ment of 5a (300 mg, 2.08 mmol, 30 h) according to the general pro-
cedure, after purification (cyclohexane/ethyl acetate, 20:1, 10:1),
gave 6b (184 mg, 38%) as a colourless solid (50% of 5a was reco-
(70 eV; EI): m/z (%)
73 (100) [Si(CH3)3 ].
307 (30) [M ], 306 (54), 218 (51), 77 (22),
C19H21NOSi (307.47): calcd. C 74.22, H
6.88, N 4.56; found C 74.19, H 6.98, N 4.66.
˜
vered).
M.p. 122 123 °C (ethanol).
IR (CCl4): ν
3310
(ϵC H), 3065, 1700, 1595, 1540, 1485, 1415, 1200, 1105, 1070, {[2 -(But-2 -ynyl)phenyl]methylene}methylamine N-Oxide (6f):
1
4
1025 cm
.
1H NMR (250 MHz): δ
2.26 (t, J3
2.7 Hz, Treatment of 5f (535 mg, 3.38 mmol, 2.5 h) according to the general
,1
4
1 H, 3 -H), 3.69 (d, J1
2.7 Hz, 2 H, 1 -H), 7.41 7.44 (m, procedure, after purification (cyclohexane/ethyl acetate, 1:2), gave
,3
3 H, Ar-H), 7.46 (mc, 3 H, Ar-H), 7.77 7.83 (m, 2 H, Ar-H), 8.26
6f (533 mg, 84%) as colourless crystals, m.p. 99 100 °C (ethanol).
IR (CCl4): ν˜ 2945, 2920, 1715, 1560, 1420, 1260, 1190, 1175,
(s, 1 H, 1-H), 9.22 9.33 (m, 1 H, 6 -H). 13C NMR (100 MHz):
1
5
δ
23.7 (C-1 ), 71.7 (C-3 ), 81.3 (C-2 ), 121.9 (Ar-C), 127.7 (Ar-
1070 cm
.
1H NMR (250 MHz): δ
1.82 (t, J4
2.6 Hz,
2.6 Hz, 2 H, 1 -H), 3.92 (s, 3 H,
NCH3), 7.30 7.42 (m, 3 H, Ar-H), 7.70 (s, 1 H, 1-H), 9.01 9.15
EI): m/z (%) 235 (29) [M ], 218 (100), 206 (79), 115 (84), 77 (46). (m, 1 H, 6 -H). 13C NMR (100 MHz): δ 3.9 (C-4 ), 23.7 (C-
,1
C), 128.6 (Ar-C), 128.7 (Ar-Cq), 129.3 (Ar-C), 130.1 (Ar-C), 130.9 3 H, 4 -H), 3.55 (q, 5J1
,4
(Ar-C), 131.4 (C-1), 135.0 (Ar-Cq), 149.6 (Ar-Cq).
MS (70 eV;
C16H13NO (235.28): calcd. C 81.68, H 5.57, N 5.95; found C
81.48, H 5.50, N 5.72.
1 ), 55.0 (NCH3), 76.0 (C-2 /3 ), 79.1 (C-2 /3 ), 127.2 (Ar-C),
128.3 (Ar-C), 128.4 (Ar-Cq), 129.1 (Ar-C), 130.3 (Ar-C), 131.9 (C-
1), 135.8 (Ar-Cq). MS (70 eV; EI): m/z (%) 187 (13) [M ], 186
(37), 172 (41), 144 (100), 115 (31). C12H13NO (187.24): calcd. C
76.98, H 7.00, N 7.48; found C 76.76, H 7.06, N 7.22.
tert-Butyl{[2 -(prop-2 -ynyl)phenyl]methylene}amine N-Oxide (6c):
A suspension of N-tert-butylhydroxylamine hydrochloride (113 mg,
0.90 mmol) and sodium acetate (170 mg, 2.08 mmol) in dry CH2Cl2
(5 mL) was stirred for 15 min and then treated with 5a (100 mg,
N-{[2 -(But-2 -ynyl)phenyl]methylene}aniline N-Oxide (6g): Treat-
0.69 mmol). After this had stirred for 72 h at room temp., water ment of 5f (350 mg, 2.21 mmol, 28 h) according to the general pro-
(15 mL) was added and the mixture was extracted with CH2Cl2 (3 cedure, after purification (cyclohexane/ethyl acetate, 40:1, 10:1),
10 mL). The combined organic phases were washed with brine, gave 6g (390 mg, 71%) as a beige solid (15% of 5f was recovered).
dried (MgSO4), and concentrated in vacuo. Purification of the res- M.p. 99 100 °C (ethanol). IR (CCl4): ν˜ 3070, 2920, 2855,
idue by flash chromatography (SiO2; cyclohexane/ethyl acetate, 5:1) 1705, 1595, 1545, 1490, 1460, 1410, 1295, 1205, 1105, 1070, 1025
Eur. J. Org. Chem. 2001, 3313 3332
3321

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
1
5
cm
.
1H NMR (250 MHz): δ
1.84 (t, J4
2.6 Hz, 3 H, 2.34 (s, 3 H, CH3), 3.83 (s, 2 H, 1 -H), 3.93 (s, 3 H, NCH3), 7.10
,1
5
4 -H), 3.62 (q, J1
2.6 Hz, 2 H, 1 -H), 7.38 7.58 (m, 6 H, (mc, 1 H, Ar-H), 7.29 (mc, 1 H, Ar-H), 7.34 7.41 (m, 2 H, Ar-H),
,4
Ar-H), 7.75 7.88 (m, 2 H, Ar-H), 8.32 (s, 1 H, 1-H), 9.30 9.41 7.43 7.49 (m, 2 H, Ar-H), 7.76 (s, 1 H, 1-H), 9.06 (mc, 1 H, 6 -
(m, 1 H, 6 -H). 13C NMR (100 MHz): δ 3.6 (C-4 ), 24.1 (C- H). 13C NMR (100 MHz): δ
21.5 (CH3), 24.4 (C-1 ), 55.0
1 ), 76.3 (C-2 /3 ), 79.2 (C-2 /3 ), 121.9 (Ar-C), 127.5 (Ar-C), (NCH3), 83.7 (C-2 /3 ), 85.8 (C-2 /3 ), 120.2 (Ar-Cq), 127.4 (Ar-
128.5 (Ar-C), 128.7 (Ar-Cq), 129.2 (Ar-C), 129.3 (Ar-C), 130.0 (Ar- C), 128.4 (Ar-C), 128.6 (Ar-Cq), 129.2 (Ar-C), 130.4 (Ar-C), 131.5
C), 130.9 (Ar-C), 131.6 (C-1), 136.5 (Ar-Cq), 149.7 (Ar-Cq). MS (Ar-C), 131.9 (C-1), 135.0 (Ar-Cq), 138.2 (Ar-Cq).
MS (70 eV;
(70 eV; EI): m/z (%) 249 (11) [M] , 206 (23), 141 (22), 115 (27),
EI): m/z (%) 263 (12) [M ], 235 (32), 144 (50), 119 (100), 91 (51).
77 (64). HRMS (C17H15NO): calcd. 249.1154: found 249.1152.
C18H17NO (263.34): calcd. C 81.90, H 6.06, N 5.62; found C
81.67, H 6.07, N 5.58.
Methyl{[2 -(3 -phenylprop-2 -ynyl)phenyl]methylene}amine N-
Oxide (6h): Treatment of 5h (290 mg, 1.32 mmol, 4 h) according to
the general procedure, after purification (cyclohexane/ethyl acetate,
1:2), gave 6h (207 mg, 63%) as a beige solid, m.p. 110 112 °C (eth-
Methyl{[4 ,5 -dimethoxy-2 -(prop-2 -ynyl)phenyl]methylene}amine
N-Oxide (6l): Treatment of 5l (500 mg, 2.45 mmol, 6 h) according
to the general procedure, after purification (cyclohexane/ethyl acet-
˜
anol). IR (CCl4): ν 3060, 3020, 2945, 1715, 1560, 1490, 1420, ate, 1:2; ethyl acetate), gave 6l (434 mg, 76%) as colourless crystals,
1
1190, 1170 cm
.
1H NMR (250 MHz): δ
3.86 (s, 2 H, 1 -
m.p. 118 120 °C (ethanol, decomp.).
IR (CCl4): ν˜
3310
H), 3.94 (s, 3 H, NCH3), 7.22 7.57 (m, 8 H, Ar-H), 7.79 (s, 1 H, (ϵC H), 2995, 2930, 2825, 1600, 1505, 1460, 1285, 1230, 1075,
1
4
1-H), 9.00 9.11 (m, 1 H, 6 -H). 13C NMR (100 MHz): δ 24.4 1010 cm
(C-1 ), 55.1 (NCH3), 83.7 (C-2 /3 ), 86.6 (C-2 /3 ), 123.3 (Ar-
1 H, 3 -H), 3.59 (d, 4J1
Cq), 128.2 (Ar-C), 128.3 (Ar-C), 128.4 (Ar-C), 128.6 (Ar-Cq), 129.3 CH3), 3.92 (s, 3 H, CH3), 3.93 (s, 3 H, CH3), 6.94 (s, 1 H, 3 -H),
.
1H NMR (250 MHz): δ
2.25 (t, J3
2.7 Hz,
,1
2.7 Hz, 2 H, 1 -H), 3.91 (s, 3 H,
,3
(Ar-C), 130.4 (Ar-C), 131.6 (Ar-C), 131.8 (C-1), 134.9 (Ar-Cq).
7.58 (s, 1 H, 1-H), 9.01 (s, 1 H, 6 -H).
13C NMR (100 MHz):
22.8 (C-1 ), 54.8 (NCH3), 55.9 (OCH3), 56.0 (OCH3), 71.6 (C-
MS (70 eV; EI): m/z (%) 249 (64) [M ], 220 (25), 132 (100), 105
δ
(32), 77 (24).
249.1154.
HRMS (C17H15NO): calcd. 249.1152; found
3 ), 81.2 (C-2 ), 111.3 (C-3 /6 ), 112.2 (C-3 /6 ), 121.2 (C-1 /2 ),
127.9 (C-1 /2 ), 131.5 (C-1), 147.4 (C-4 /5 ), 150.2 (C-4 /5 ). MS
(70 eV; EI): m/z (%) 233 (54) [M ], 216 (78), 194 (70), 188 (100)
[M NOCH3] , 185 (46). C13H13NO3 (233.27): calcd. C 66.94,
H 6.48, N 6.00; found C 66.77, H 6.49, N 5.80.
N-{[2 -(3 -Phenylprop-2 -ynyl)phenyl]methylene}aniline N-Oxide
(6i): Treatment of 5h (263 mg, 1.54 mmol, 8 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
30:1, 3:1), gave 6i (796 mg, 55%) as a pale yellow, noncrystalline N-{[4 ,5 -Dimethoxy-2 -(prop-2 -ynyl)phenyl]methylene}aniline N-
˜
solid (19% of 5h was recovered).
2945, 1560, 1490, 1420, 1190, 1170 cm
δ
IR (CCl4): ν
3065, 3020,
1H NMR (250 MHz): to the general procedure, after purification (cyclohexane/ethyl acet-
ate, 10:1), gave 6m (207 mg, 36%) as a beige solid (32% of 5l was
MS recovered). M.p. 130 134 °C (ethanol, decomp.). IR (CCl4):
Oxide (6m): Treatment of 5l (400 mg, 1.96 mmol, 45 h) according
1
.
3.91 (s, 2 H, 1 -H), 7.25 7.50 (m, 11 H, Ar-H), 7.75 7.85
(m, 2 H, Ar-H), 8.41 (s, 1 H, 1-H), 9.35 (mc, 1 H, 6 -H).
(170 eV; CI, isobutane): m/z (%)
C6H5] , 221 (8), 205 (8), 105 (5).
306 (2), 250 (100), 234 (4) [M 3310 (ϵC H), 3000, 2935, 2830, 1695, 1600, 1500, 1465, 1280,
1
1115, 1010 cm
.
1H NMR (250 MHz): δ
2.29 (t, 4J3
,1
4
2.8 Hz, 1 H, 3 -H), 3.65 (d, J1
2.8 Hz, 2 H, 1 -H), 3.96 (s,
,3
tert-Butyl{[2 -(3 -phenylprop-2 -ynyl)phenyl]methylene}amine N-
Oxide (6j): A suspension of N-tert-butylhydroxylamine hydro-
chloride (60 mg, 0.45 mmol) and sodium acetate (90 mg,
1.10 mmol) in dry CH2Cl2 (5 mL) was stirred for 15 min and then
treated with 5h (81 mg, 0.37 mmol). After this had stirred for 24 h
at room temp., water (15 mL) was added and the mixture was ex-
3 H, OCH3), 3.99 (s, 3 H, OCH3), 6.96 (s, 1 H, 3 -H), 7.45 7.54
(m, 3 H, Ar-H), 7.76 7.83 (m, 2 H, Ar-H), 8.19 (s, 1 H, 1-H), 9.29
(s, 1 H, 6 -H).
13C NMR (100 MHz): δ
23.1 (C-1 ), 56.0
(OCH3), 56.1 (OCH3), 71.2 (C-3 ), 81.3 (C-2 ), 111.5 (Ar-C),
112.5 (Ar-C), 121.5 (Ar-Cq), 121.8 (Ar-C), 129.2 (Ar-Cq), 129.8
(Ar-C), 131.2 (C-1), 147.5 (Ar-Cq), 149.5 (Ar-Cq), 150.7 (Ar-Cq).
tracted with CH2Cl2 (3
10 mL). The combined organic phases
MS (70 eV; EI): m/z (%)
295 (44) [M ], 278 (100), 256 (60),
were washed with brine, dried (MgSO4), and concentrated in vacuo.
Purification of the residue by flash chromatography (SiO2; cyclo-
hexane/ethyl acetate, 2:1) afforded 6j (84 mg, 78%) as colourless
188 (34), 77 (60).
295.1212.
HRMS (C18H17NO3): calcd. 295.1208; found
˜
.
crystals, m.p. 117 118 °C (ethanol). IR (CCl4): ν 3065, 2975, ({4 ,4 -Dimethoxy-2 -[3 -(trimethylsilyl)prop-2 -ynyl]phenyl}-
1
2930, 1555, 1490, 1470, 1360, 1195, 1135 cm
1H NMR
methylene)methylamine N-Oxide (6n): Treatment of 5n (350 mg,
(250 MHz): δ 1.62 (s, 9 H, CH3), 3.85 (s, 2 H, 1 -H), 7.24 7.31 1.27 mmol, 7 h) according to the general procedure, after purifica-
(m, 3 H, Ar-H), 7.33 7.44 (m, 5 H, Ar-H), 8.04 (s, 1 H, 1-H), tion (ethyl acetate), gave 6n (271 mg, 70%) as pale yellow crystals,
13C NMR (125 MHz): δ
24.8 (C-
m.p. 122 124 °C (ethanol).
IR (CCl4): ν
3000, 2960, 2830,
˜
9.07 9.16 (m, 1 H, 6 -H).
1 ), 28.4 (CH3), 71.5 (Cq), 83.3 (C-2 /3 ), 86.9 (C-2 /3 ), 123.3 2175 (CϵC), 1600, 1510, 1465, 1425, 1300, 1285, 1250, 1225, 1075
1
(Ar-Cq), 126.7 (C-1), 127.5 (Ar-C), 128.1 (Ar-C), 128.3 (Ar-C), cm
.
1H NMR (250 MHz): δ 0.17 (s, 9 H, SiMe3), 3.45 (s, 3
128.5 (Ar-C), 129.2 (Ar-Cq), 129.3 (Ar-C), 130.0 (Ar-C), 131.5 (Ar- H, NCH3) 3.73 (s, 3 H, OCH3), 3.76 (s, 3 H, OCH3), 6.79 (s, 1 H,
C), 135.3 (Ar-Cq). MS (70 eV; EI): m/z (%) 291 (3) [M ], 234
3 -H), 7.44 (s, 1 H, 1-H), 8.85 (s, 1 H, 6 -H).
13C NMR
(41), 206 (54), 130 (43), 105 (49), 57 (100) [C(CH3)3 ]. C20H21NO (100 MHz): δ
0.0 (SiMe3), 24.2 (C-1 ), 54.7 (NCH3), 55.8
(291.39): calcd. C 82.44, H 7.26, N 4.81; found C 82.50, H 7.12, (OCH3), 56.0 (OCH3), 88.3 (C-2 ), 103.4 (C-3 ), 111.2 (C-3 /6 ),
N 4.65.
112.3 (C-3 /6 ), 121.2 (C-1 /2 ), 128.3 (C-1 /2 ), 131.7 (C-1), 147.3
(C-4 /5 ), 150.1 (C-4 /5 ). MS (70 eV; EI): m/z (%) 305 (19)
[M ], 290 (21), 262 (39), 204 (14), 73 (100) [Si(CH3)3 ]. HRMS
(C16H23NO3Si): calcd. 305.1447; found 305.1447.
Methyl{[2 -(3 -phenylprop-2 -ynyl)phenyl]methylene}amine N-
Oxide (6k): Treatment of 5k (180 mg, 0.78 mmol, 4.5 h) according
to the general procedure, after purification (cyclohexane/ethyl acet-
ate, 3:1, 1:1), gave 6k (258 mg, 70%) as colourless crystals, m.p.
110 112 °C (ethanol).
1510, 1460, 1420, 1170, 1020 cm
({4 ,5 -Dimethoxy-2 -[3 -(4 -methylphenyl)but-2 -ynyl]phenyl}-
methylene)methylamine N-Oxide (6o): Treatment of 5o (474 mg,
1.61 mmol, 6 h) according to the general procedure, after purifica-
IR (CCl4): ν˜
3025, 2925, 2870, 1605,
1
.
1H NMR (250 MHz): δ
3322
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
tion (ethyl acetate/methanol, 10:1), gave 6o (485 mg, 87%) as col- 5:1), gave 9d (36 mg, 24%) and 9a (31 mg, 29%; see above), both
ourless crystals, m.p. 141 143 °C (ethanol, decomp.). IR (CCl4): as colourless solids. Compound 9d: M.p. 104 106 °C (ethanol).
˜
IR (CCl
2.34 (s, 3 H, CH3), 3.79 cm .
˜
ν
3000, 2935, 2830, 1600, 1510, 1465, 1285, 1230, 1175, 1075,
4): ν
2955, 1625 (C O), 1425, 1395, 1335, 1245, 1120
1
1
1010 cm
.
1H NMR (250 MHz): δ
1H NMR (250 MHz): δ 0.30 (s, 9 H, SiMe3), 3.06 (s, 3
4
(s, 2 H, 1 -H), 3.90 (d, JNCH3,1 0.6 Hz, 3 H, NCH3), 3.93 (s, 3 H, NCH3), 4.12 (s, 2 H, 1-H), 7.20 (s, 1 H, 5-H), 7.21 7.40 (m, 4
H, OCH3), 3.94 (s, 3 H, OCH3), 6.99 (s, 1 H, 3 -H), 7.10 (mc, 2 H, H, Ar-H).
Ar-H), 7.28 (mc, 2 H, Ar-H), 7.68 (mc, 1 H, 1-H), 9.04 (s, 1 H, 6 - (NCH3), 53.1 (C-1), 126.9 (Ar-C), 128.3 (Ar-C), 128.7 (Ar-C),
H). 21.4 (CH3), 23.8 (C-1 ), 54.8 129.0 (Ar-C), 136.7 (Ar-Cq/C-4), 137.0 (Ar-Cq/C-4), 141.5 (C-5),
13C NMR (100 MHz): δ
13C NMR (100 MHz): δ
0.7 (SiMe3), 34.5
(NCH3), 55.9 (OCH3), 56.0 (OCH3), 83.8 (C-2 /3 ), 85.9 (C-2 / 144.0 (Ar-Cq), 169.2 (C-3). MS (70 eV; EI): m/z (%) 245 (12)
3 ), 111.3 (Ar-C), 112.3 (Ar-C), 120.1 (Ar-C), 121.3 (Ar-C), 128.9 [M ], 230 (100), 132 (13), 115 (28), 73 (11) [Si(CH3)3 ].
(C-1 /2 ), 129.1 (C-3 /6 ), 131.4 (C-3 /6 ), 131.8 (C-1), 138.3 (C-1 / C14H19NOSi (245.40): calcd. C 68.52, H 7.80, N 5.71; found C
2 ), 147.3 (C-4 /5 ), 150.2 (C-4 /5 ).
MS (70 eV; EI): m/z (%)
68.49, H 7.81, N 5.87.
323 (79) [M ], 308 (19), 278 (24), 204 (72), 119 (100). C20H21NO3
(323.39): calcd. C 74.13, H 6.62, N 4.32; found C 74.28, H 6.55,
N 4.33.
1,2-Dihydro-2-phenyl-4-(trimethylsilyl)-3H-2-benzazepin-3-one (9e):
Treatment of 6e (110 mg, 0.36 mmol; KOH, 2 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
20:1, 3:1), gave 9e (75 mg, 68%) and 9b (22 mg, 26%; see above),
1,2-Dihydro-2-methyl-3H-2-benzazepin-3-one (9a): Treatment of 6a
(50 mg, 0.29 mmol; NaOMe, 30 min) according to the general pro- both as colourless solids. Compound 9e: M.p. 111 112 °C (eth-
cedure, after purification (cyclohexane/ethyl acetate, 1:1, 1:2), gave
9a (42 mg, 84%) as colourless crystals, m.p. 132 133 °C (ethanol).
anol).
s, 2 H, 1-H), 7.16 7.46 (m, 10 H, 5-H, Ar-H).
1H NMR (250 MHz): δ 0.34 (s, 9 H, SiMe3), 4.55 (br.
13C NMR
˜
IR (CCl4): ν 3065, 3020, 2920, 1650 (C O), 1615, 1475, 1430, (100 MHz): δ
0.0 (SiMe3), 55.1 (C-1), 127.3 (Ar-C), 127.5 (Ar-
1
1400, 1345, 1220, 1105 cm
.
1H NMR (250 MHz): δ 3.11 (s, C), 127.8 (Ar-C), 129.1 (Ar-C), 129.7 (Ar-C), 129.8 (Ar-C), 129.9
3
3 H, NCH3), 4.24 (s, 2 H, 1-H), 6.41 (d, J4,5
12.2 Hz, 1 H, 4- (Ar-C), 137.8 (Ar-Cq), 137.9 (C-4), 142.9 (C-5), 144.0 (Ar-Cq),
H), 7.08 (d, 3J5,4 12.2 Hz, 1 H, 5-H), 7.25 7.44 (m, 4 H, Ar-H). 144.7 (Ar-Cq), 169.6 (C-3). MS (70 eV; EI): m/z (%) 307 (16)
13C NMR (100 MHz): δ
35.0 (NCH3), 53.4 (C-1), 127.3 (C- [M ], 292 (17), 194 (100), 115 (9), 77 (10). C19H21NOSi (307.47):
4), 127.6 (Ar-C), 128.4 (Ar-C), 129.2 (Ar-C), 129.3 (Ar-C), 135.4 calcd. C 74.22, H 6.88, N 4.56; found C 73.85, H 7.10, N 4.58.
(Ar-Cq), 136.2 (Ar-Cq), 136.3 (C-5), 166.3 (C-3). MS (70 eV; EI):
1,2-Dihydro-2,4-dimethyl-3H-2-benzazepin-3-one (9f): Treatment of
m/z (%)
173 (100) [M ], 144 (74) [M
NCH3] , 132 (18), 115
6f (145 mg, 0.77 mmol; 1 equiv. NaOMe, 24 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
2:1), gave 9f (124 mg, 86%) as colourless crystals, m.p. 114 115 °C
(34). C11H11NO (173.21): calcd. C 76.28, H 6.40, N 8.09; found
C 76.29, H 6.51, N 8.15.
˜
1,2-Dihydro-2-phenyl-3H-2-benzazepin-3-one (9b): Treatment of 6b
(ethanol).
IR (CCl4): ν
2950, 2925, 1645 (C O), 1620, 1475,
1
(114 mg, 0.48 mmol; KOH, 2 h) according to the general procedure, 1450, 1425, 1395, 1265, 1215, 1070, 1010 cm
.
1H NMR
after purification (cyclohexane/ethyl acetate, 10:1, 3:1), gave 9b
(250 MHz): δ 2.20 (d, 4JCH3,5 1.5 Hz, 3 H, CH3), 3.01 (s, 3 H,
4
(97 mg, 84%) as colourless crystals, m.p. 109 110 °C (diethyl ether, NCH3), 4.10 (br. s, 2 H, 1-H), 6.89 (q, J5,CH3
1.5 Hz, 1 H, 5-
H), 7.12 7.31 (m, 4 H, Ar-H). 13C NMR (100 MHz): δ 21.7
(CH3), 34.7 (NCH3), 53.2 (C-1), 126.8 (Ar-C), 128.1 (Ar-C), 128.9
˜
decomp.). IR (CCl4): ν 3065, 3030, 2905, 1650 (C O), 1595,
1
1495, 1440, 1415, 1340, 1290, 1215, 1100 cm
.
1H NMR
3
(250 MHz): δ
4-H), 7.20 (d, J5,4
H).
4.66 (s, 2 H, 1-H), 6.55 (d, J4,5
12.2 Hz, 1 H, (Ar-C), 132.3 (C-5), 135.9 (Cq), 136.0 (Cq), 136.1 (Cq), 167.5 (C-3).
12.2 Hz, 1 H, 5-H), 7.21 7.50 (m, 9 H, Ar- MS (70 eV; EI): m/z (%) 187 (100) [M ], 172 (46), 158 (39),
13C NMR (100 MHz): δ
54.8 (C-1), 126.4 (Ar-C/C-4), 144 (46), 132 (37), 115 (30). C12H13NO (187.24): calcd. C 76.98,
3
126.9 (Ar-C/C-4), 127.5 (Ar-C/C-4), 127.7 (Ar-C/C-4), 128.6 (Ar- H 7.00, N 7.48; found C 76.73, H 6.98, N 7.37.
C/C-4), 129.2 (Ar-C/C-4), 129.4 (Ar-C/C-4), 129.5 (Ar-C/C-4),
1,2-Dihydro-4-methyl-2-phenyl-3H-2-benzazepin-3-one (9g): Treat-
135.5 (Ar-Cq), 136.7 (Ar-Cq), 136.8 (C-5), 143.1 (Ar-Cq), 165.8 (C-
ment of 6g (160 mg, 0.64 mmol; 1 equiv. NaOMe, 20 h) according
to the general procedure, after purification (cyclohexane/ethyl acet-
ate, 10:1), gave 9g (100 mg, 62%) as colourless crystals, m.p.
3).
MS (70 eV; EI): m/z (%)
235 (100) [M ], 206 (88), 194
(90), 115 (35), 77 (16).
C16H13NO (235.28): calcd. C 81.68, H
5.57, N 5.95; found C 81.70, H 5.62, N 5.87.
˜
128 130 °C (ethanol).
IR (CCl4): ν
3065, 3030, 2920, 1650
1
2-tert-Butyl-1,2-dihydro-3H-2-benzazepin-3-one (9c): Treatment of
(C O), 1620, 1595, 1500, 1440, 1335, 1215, 1090 cm
6c (100 mg, 0.46 mmol, KOH, 4 h) according to the general proced- NMR (250 MHz): δ 2.34 (d, JCH3,5 1.2 Hz, 3 H, CH3), 4.57
.
1H
4
4
ure, after purification (cyclohexane/ethyl acetate, 5:1), gave 9c
(85 mg, 85%) as a colourless solid, m.p. 146 147 °C (ethanol).
(br. s, 2 H, 1-H), 7.06 (q, J5,CH3
1.2 Hz, 1 H, 5-H), 7.15 7.44
(m, 9 H, Ar-H). 13C NMR (100 MHz): δ 21.9 (CH3), 54.5 (C-
IR (CCl4): ν˜
3025, 2970, 1640 (C O), 1410, 1365, 1340, 1195, 1), 126.7 (Ar-C), 126.8 (Ar-C), 126.9 (Ar-C), 128.3 (Ar-C), 128.4
1
1100 cm
.
1H NMR (250 MHz): δ
1.48 (s, 3 H, CH3), (Ar-C), 129.0 (Ar-C), 129.1 (Ar-C), 133.0 (C-5), 135.7 (Cq), 136.0
MS (70 eV; EI): m/z
3
3.96 4.40 (m, 2 H, 1-H), 6.36 (d, J4,5 12.1 Hz, 1 H, 4-H), 6.98 (Cq), 136.4 (Cq), 143.3 (Cq), 167.1 (C-3).
3
(d, J5,4
12.1 Hz, 1 H, 5-H), 7.30 7.39 (m, 4 H, Ar-H).
13C (%)
249 (77) [M ], 220 (13), 194 (100), 128 (13), 77 (18).
HRMS (C17H15NO): calcd. 249.1154; found 249.1155.
NMR (100 MHz): δ 29.0 (CH3), 47.2 (C-1), 58.1 (Cq), 126.8 (C-
4), 128.1 (Ar-C), 129.0 (Ar-C), 129.4 (Ar-C), 130.3 (Ar-C), 135.0
(C-5), 135.8 (Ar-Cq), 138.7 (Ar-Cq), 167.6 (C-3). MS (70 eV; EI):
1,2-Dihydro-2-methyl-4-phenyl-3H-2-benzazepin-3-one (9h): Treat-
ment of 6h (190 mg, 0.76 mmol; KOH, 4 h) according to the gen-
eral procedure, after purification (cyclohexane/ethyl acetate, 2:1),
gave 9h (142 mg, 75%) as colourless crystals, m.p. 116 °C (ethanol).
m/z (%)
215 (54) [M ], 159 (100), 142 (43), 115 (46), 58 (13)
[C(CH3)3 ]. C14H17NO (215.29): calcd. C 78.10, H 7.96, N 6.51;
found C 78.14, H 7.83, N 6.31.
˜
IR (CCl4): ν 3060, 3020, 2920, 1645 (C O), 1485, 1445, 1425,
1
1,2-Dihydro-2-methyl-4-(trimethylsilyl)-3H-2-benzazepin-3-one (9d): 1395, 1185, 1000 cm
.
1H NMR (250 MHz): δ 3.13 (s, 3 H,
Treatment of 6d (150 mg, 0.61 mmol; NaOMe, 2 h) according to
the general procedure, after purification (cyclohexane/ethyl acetate,
NCH3), 4.29 (br. s, 2 H, 1-H), 7.29 7.46 (m, 8 H, 5-H, Ar-H),
7.64 7.68 (m, 2 H, Ar-H).
13C NMR (100 MHz): δ
34.4
Eur. J. Org. Chem. 2001, 3313 3332
3323

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
(NCH3), 53.2 (C-1), 126.9 (Ar-C), 128.0 (Ar-C), 128.2 (Ar-C), 110.5 (Ar-C), 112.0 (Ar-C), 126.0 (C-4), 128.3 (C-5a/9a), 129.6 (C-
128.4 (Ar-C), 128.6 (Ar-C), 129.6 (Ar-C), 131.7 (C-5), 135.9 (Cq), 5a/9a), 136.2 (C-5), 148.8 (C-7/8), 149.8 (C-7/8), 166.5 (C-3). MS
136.1 (Cq), 139.1 (Cq), 139.7 (Cq), 166.6 (C-3).
m/z (%) 249 (77) [M ], 220 (24) [M NCH3] , 192 (16), 144 NCH3] , 190 (18), 160 (10).
C17H15NO (249.31): calcd. C 81.90, H 6.06, N 233.1052; found 233.1052.
MS (70 eV; EI): (70 eV; EI): m/z (%)
233 (100) [M ], 218 (17), 204 (37) [M
HRMS (C13H15NO3): calcd.
(39), 132 (100).
5.62; found C 81.93, H 6.03, N 5.48.
1,2-Dihydro-7,8-dimethoxy-2-phenyl-3H-benzazepin-3-one
(9m):
Treatment of 6m (100 mg, 0.34 mmol; KOH, 2 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
1:2), gave 9m (93 mg, 93%) as colourless crystals, m.p. 143 144 °C
1,2-Dihydro-2,4-diphenyl-3H-2-benzazepin-3-one (9i): Treatment of
6i (100 mg, 0.32 mmol; NaOMe, 4 h) according to the general pro-
cedure, after purification (cyclohexane/ethyl acetate, 1:2), gave 9i
(40 mg, 40%) as a colourless solid, m.p. 154 156 °C (diethyl ether).
(ethanol). IR (CCl4): ν˜ 3005, 2930, 2840, 1640 (C O), 1605,
1
1520, 1495, 1380, 1280, 1200, 1175, 1095 cm
.
1H NMR
˜
IR (CCl4): ν 3065, 3030, 1655 (C O), 1595, 1495, 1440, 1405,
1
1330, 1190, 1105 cm
.
1H NMR (250 MHz): δ 4.72 (br. s, 2
(250 MHz): δ 3.88 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3), 4.58 (s,
2 H, 1-H), 6.44 (d, 3J4,5 12.2 Hz, 1 H, 4-H), 6.74 (s, 1 H, Ar-H),
H, 1-H), 7.23 7.59 (m, 13 H, 5-H, Ar-H), 7.78 (mc, 2 H, Ar-H).
13C NMR (100 MHz): δ 54.7 (C-1), 126.7 (Ar-C), 127.0 (Ar-
C), 127.1 (Ar-C), 128.1 (Ar-C), 128.3 (Ar-C), 128.4 (Ar-C), 128.6
(Ar-C), 129.0 (Ar-C), 129.2 (Ar-C), 129.9 (Ar-C), 132.6 (C-5), 136.0
(C-4), 136.7 (Ar-Cq), 139.3 (Ar-Cq), 139.4 (Ar-Cq), 143.0 (Ar-Cq),
166.3 (C-3). MS (70 eV; EI): m/z (%) 311 (24) [M ], 194 (100),
3
6.91 (s, 1 H, Ar-H), 7.09 (d, J5,4
12.2 Hz, 1 H, 5-H), 7.26 (mc,
3 H, Ar-H), 7.38 (mc, 2 H, Ar-H).
13C NMR (100 MHz): δ
54.5 (OCH3), 56.1 (C-1), 110.5 (C-6/9), 112.2 (C-6/9), 125.9 (C-4),
126.4 (Ar-C), 126.9 (Ar-C) 128.4 (Ar-Cq), 129.2 (Ar-C), 130.0 (Ar-
Cq), 136.9 (C-5), 143.1 (Ar-Cq), 149.0 (C-7/8), 150.0 (C-7/8), 166.1
(C-3).
MS (70 eV; EI): m/z (%)
295 (71) [M ], 266 (74), 149
HRMS (C18H17NO3): calcd.
116 (5), 77 (8).
4.50; found C 84.78, H 5.54, N 4.44.
C22H17NO (311.38): calcd. C 84.86, H 5.50, N
(52), 77 (31), 69 (64), 57 (100).
295.1208; found 295.1206.
2-(tert-Butyl)-1,2-dihydro-4-phenyl-3H-2-benzazepin-3-one
(9j):
1,2-Dihydro-7,8-dimethoxy-2-methyl-4-trimethylsilyl-3H-2-benz-
azepin-3-one (9n): Treatment of 6n (91 mg, 0.30 mmol; KOH, 2 h)
according to the general procedure, after purification (cyclohexane/
ethyl acetate, 2:1, 1:2), gave 9n (23 mg, 25%) and 9l (30 mg, 43%;
see above), both as colourless solids. Compound 9n: M.p. 134 135
Treatment of 6j (60 mg, 0.21 mmol; NaOMe, 8 h) according to the
general procedure, after purification (cyclohexane/ethyl acetate,
10:1), gave 9j (48 mg, 80%) as a colourless solid, m.p. 130 131 °C
˜
(ethanol).
IR (CCl4): ν
3065, 3025, 2975, 2925, 1640 (C O),
1
1485, 1400, 1330, 1205, 1185, 1110 cm
.
1H NMR (250 MHz):
1.50 (s, 9 H, CH3), 4.24 (d, J 15.3 Hz, 1 H, 1-Ha), 4.53 (d,
15.3 Hz, 1 H, 1-Hb), 7.20 (s, 1 H, 5-H), 7.26 7.45 (m, 7 H,
13C NMR (100 MHz): δ
29.3
2
˜
°C (diethyl ether).
IR (CCl4): ν
3005, 2950, 2900, 1620 (C
δ
2J
1
O), 1515, 1460, 1390, 1260, 1200, 1120 cm
.
1H NMR
(250 MHz): δ 0.29 (s, 9 H, SiMe3), 3.06 (s, 3 H, NCH3), 3.90 (s,
Ar-H), 7.61 (mc, 2 H, Ar-H).
3 H, OCH3), 3.93 (s, 3 H, OCH3), 4.08 (s, 2 H, 1-H), 6.76 (s, 1 H,
(CH3), 47.3 (C-1), 58.4 (Cq), 126.5 (Ar-C), 127.7 (Ar-C), 128.0 (Ar-
C), 128.2 (Ar-C), 128.3 (Ar-C), 128.4 (Ar-C), 129.6 (Ar-C), 130.2
(C-5), 136.2 (Cq), 138.3 (Cq), 140.0 (Cq), 141.8 (Cq), 167.5 (C-3).
Ar-H), 6.86 (s, 1 H, Ar-H), 7.13 (s, 1 H, 5-H).
(100 MHz): δ 0.6 (SiMe3), 34.6 (NCH3), 52.8 (C-1), 56.2
(OCH3), 110.1 (C-6/9), 111.9 (C-6/9), 130.0 (Cq), 130.1 (Cq), 141.4
(C-5), 142.0 (Cq), 148.1 (C-7/8), 149.5 (C-7/8), 169.4 (C-3). MS
(70 eV; EI): m/z (%) 305 (15) [M ], 290 (100), 274 (16), 221 (24),
73 (21) [Si(CH3)3 ]. C16H23NO3Si (305.45): calcd. C 62.92, H
13C NMR
MS (70 eV; EI): m/z (%)
291 (47) [M ], 235 (100), 234 (71),
191 (22), 118 (18).
291.1624.
HRMS (C20H21NO): calcd. 291.1623; found
1,2-Dihydro-2-methyl-4-(4 -methylphenyl)-3H-2-benzazepin-3-one
(9k): Treatment of 6k (92 mg, 0.35 mmol; KOH, 5 h) according to
the general procedure, after purification (cyclohexane/ethyl acetate,
5:1), gave 9k (59 mg 64%) as colourless crystals, m.p. 99 100 °C
7.59, N 4.59; found C 62.85, H 7.40, N 4.55.
1,2-Dihydro-7,8-dimethoxy-2-methyl-4-(4 -methylphenyl)-3H-2-
benzazepin-3-one (9o) and 1-(5 ,6 -Dimethoxy-2 -methyl-2 H-isoin-
dol-1 -yl)-2-(4 -methylphenyl)ethan-1-one (20o): Treatment of 6o
(450 mg, 1.39 mmol; KOH, 5 h) according to the general procedure,
after purification (cyclohexane/ethyl acetate, 5:1), gave 9o (340 mg,
(ethanol).
1450, 1395, 1335, 1180, 1115, 1000 cm
2.37 (s, 3 H, CH3), 3.13 (s, 3 H, NCH3), 4.28 (br. s, 2 H, 1-H),
IR (CCl4): ν˜
3025, 2965, 2925, 1645 (C O), 1510,
1
.
1H NMR (500 MHz):
δ
76%) and 20o (54 mg, 12%).
m.p. 181 182 °C (ethanol).
Compound 9o: Colourless crystals,
7.20 (mc, 2 H, Ar-H), 7.28 (s, 1 H, 5-H), 7.29 (mc, 1 H, Ar-H), 7.32
(mc, 1 H, Ar-H), 7.37 (mc, 1 H, Ar-H), 7.42 (mc, 1 H, Ar-H), 7.56
˜
IR (CCl4): ν
3000, 2935, 2850,
1
1640 (C O), 1600, 1515, 1465, 1395, 1275, 1200, 1125, 1015 cm
.
(mc, 1 H, Ar-H).
13C NMR (125 MHz): δ
21.2 (CH3), 34.3
1H NMR (400 MHz): δ
2.36 (s, 3 H, CH3), 3.13 (s, 3 H,
(NCH3), 53.8 (C-1), 126.8 (Ar-C), 128.0 (Ar-C), 128.3 (Ar-C),
128.5 (Ar-C), 129.1 (Ar-C), 129.5 (Ar-C), 130.8 (C-5), 135.9 (Cq),
136.0 (Cq), 136.1 (Ar-Cq), 137.9 (Ar-Cq), 139.6 (Ar-Cq), 166.7 (C-
NCH3), 3.90 (s, 3 H, OCH3), 3.93 (s, 3 H, OCH3), 4.22 (br. s, 2 H,
1-H), 6.80 (s, 1 H, 6/9-H), 6.92 (s, 1 H, 6/9-H), 7.19 (mc, 2 H, Ar-
H), 7.21 (s, 1 H, 5-H), 7.54 (mc, 2 H, Ar-H).
(100 MHz): δ 21.2 (CH3), 34.5 (NCH3), 53.0 (OCH3), 56.2 (C-
1), 110.1 (C-6/9), 112.3 (C-6/9), 127.9 (Ar-C), 128.9 (Cq), 129.1 (Ar-
C), 129.4 (Cq), 130.9 (C-5), 136.4 (Cq), 137.6 (Cq), 138.2 (Cq), 148.9
13C NMR
3).
MS (70 eV; EI): m/z (%)
263 (44) [M ], 234 (16) [M
NCH3] , 189 (10), 144 (25), 132 (100).
calcd. 263.1310; found 263.1309.
HRMS (C18H17NO):
1,2-Dihydro-7,8-dimethoxy-2-methyl-3H-benzazepin-3-one
(9l):
(C-7/8), 149.3 (C-7/8), 166.9 (C-3).
MS (70 eV; EI): m/z (%)
Treatment of 6l (228 mg, 0.98 mmol; NaOMe, 1 h) according to the 324 (22) [M ], 323 (100), 308 (20), 204 (42), 149 (39). C20H21NO3
general procedure, after purification (ethyl acetate/methanol, 10:1),
gave 9l (176 mg, 77%) as colourless crystals, m.p. 124 126 °C (eth-
(323.39): calcd. C 74.28, H 6.55, N 4.33; found C 74.30, H 6.33, N
4.13. Compound 20o: Pale yellow, non-crystalline solid. IR
˜
˜
anol). IR (CCl4): ν 3005, 2930, 2850, 1645 (C O), 1600, 1520, (CCl4): ν 3005, 2935, 1705 (C O), 1500, 1425, 1375, 1305, 1220,
1
1
1460, 1380, 1265, 1195, 1110, 1010 cm
.
1H NMR (250 MHz): 1120, 1050 cm
.
1H NMR (250 MHz): δ 2.32 (s, 3 H, CH3),
δ
3.10 (s, 3 H, NCH3), 3.90 (s, 3 H, OCH3), 3.94 (s, 3 H, OCH3), 3.89 (s, 3 H, OCH3), 3.91 (s, 3 H, OCH3), 4.16 (s, 3 H, NCH3),
4.18 (s, 2 H, 1-H), 6.33 (d, 3J4,5 12.2 Hz, 1 H, 4-H), 6.81 (s, 1 H, 4.26 (s, 2 H, 2-H), 6.89 (s, 1 H, 3 -H), 7.09 7.23 (m, 6 H, Ar-H).
3
Ar-H), 6.86 (s, 1 H, Ar-H), 6.99 (d, J5,4 12.2 Hz, 1 H, 5-H).
13C NMR (100 MHz): δ
21.0 (CH3), 40.0 (NCH3), 46.5 (C-
13C NMR (100 MHz): δ 35.0 (NCH3), 53.0 (C-1), 56.1 (OCH3), 2), 55.7 (OCH3), 55.8 (OCH3), 99.1 (C-4 /7 ), 99.4 (C-4 /7 ), 119.0
3324 Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
(Cq), 121.2 (Cq), 124.7 (Ar-C), 129.3 (Ar-C), 132.3 (Cq), 136.1 (Cq), 80%) as a colourless oil, which rapidly turned yellow. IR (CCl4):
FULL PAPER
˜
147.5 (C-5 /6 ), 150.8 (C-5 /6 ), 186.1 (C-1). MS (70 eV; EI): m/
ν
2825, 2735, 1700 (C O), 1600, 1575, 1490, 1450, 1400, 1320,
1
z (%) 323 (4) [M ], 221 (100), 206 (30), 177 (27), 121 (28), 105 1295, 1195 cm
.
1H NMR (250 MHz): δ 4.10 (s, 2 H, 1 -H),
7.48 (mc, 1 H, Ar-H), 7.63 (mc, 2 H, Ar-H), 7.81 (mc, 1 H, Ar-H),
10.18 (s, 1 H, CHO). 23.9 (C-1 ),
13C NMR (125 MHz): δ
41.8 (C-3 ), 77.2 (C-2 ), 127.6 (Ar-C), 130.0 (Ar-C), 133.2 (Ar-Cq),
134.0 (Ar-C), 134.1 (Ar-C), 137.7 (Ar-Cq), 192.8 (CHO). MS
1, for 81Br], 223 (17) [M
(17). HRMS (C20H21NO3): calcd. 323.2222; found 323.2223.
2-(3 -Phenylprop-1 -ynyl)benzaldehyde (11): A degassed (Ar) solu-
tion of 2-iodobenzaldehyde[34] (619 mg, 2.67 mmol) in benzene (10
mL) was treated with PdCl2(PPh3)2 (94 mg, 0.13 mmol), CuI (ca.
5 mg), 3-phenylprop-1-yne[35] (403 mg, 3.47 mmol) and dry Et3N
(102 mg, 2.93 mmol). After this had been stirred in a sealed tube
for 2 h under Ar at room temp., dry Et3N (0.5 mL) was added and
the brown suspension was then heated for 4 h at ca. 40 °C. The
mixture was filtered and the solution was concentrated in vacuo.
Purification by flash chromatography (SiO2; cyclohexane/ethyl
acetate, 60:1) gave 11 (426 mg, 73%) as a pale red oil. IR (CCl4):
(70 eV; EI): m/z (%)
225 (15) [M
1, for 79Br], 149 (100), 143 (16) [M Br] , 115 (58). HRMS
[M , for 79Br] (C10H7BrO): calcd. 221.9680; found 221.9680.
{[2 -(3 -Bromoprop-2 -ynyl)phenyl]methylene}methylamine N-Ox-
ide (6p): Treatment of 5p (388 mg, 4.64 mmol, 4.5 h) according to
the general procedure, after purification (cyclohexane/ethyl acetate,
2:1, 1:2), gave 6p (297 mg, 33%) as a pale yellow solid, which
ν˜ 3065, 3030, 2840, 2745, 2230 (CϵC), 1700 (C O), 1595, 1495, rapidly turned brown. M.p. 87 90 °C (decomp.). IR (PTFE):
1
1
1H NMR (400 MHz): δ 3.91 (s,
ν
3025, 2935, 1700, 1595, 1580, 1415, 1300, 1160 cm
.
1H
˜
1455, 1385, 1270, 1190 cm
2 H, 3 -H), 7.28 (mc, 1 H, Ar-H), 7.33 7.38 (m, 2 H, Ar-H), NMR (250 MHz): δ
7.39 7.43 (m, 3 H, Ar-H), 7.50 7.58 (m, 2 H, Ar-H), 7.90 (mc, 1 7.35 7.39 (m, 3 H, Ar-H), 7.63 (s, 1 H, 1-H), 8.92 9.01 (m, 1 H,
.
3.64 (s, 2 H, 1 -H), 3.94 (s, 3 H, NCH3),
H, Ar-H), 10.56 (s, 1 H, CHO). 13C NMR (100 MHz): δ 26.1
6 -H). MS (170 eV; CI, isobutane): m/z (%) 254 (8) [M
1,
(C-3 ), 78.4 (C-1 ), 95.3 (C-2 ), 127.0 (Ar-C), 127.2 (Ar-C), 127.4 for 81Br], 252 (3) [M
(Ar-Cq), 128.0 (Ar-C), 128.3 (Ar-C), 128.8 (Ar-C), 133.5 (Ar-C), (100), 145 (53).
1, for 79Br], 238 (3), 236 (3), 225 (99), 223
133.8 (Ar-C), 136.1 (Ar-Cq), 136.2 (Ar-Cq), 192.0 (CHO).
(70 eV; EI): m/z (%) 220 (73) [M ], 219 (100), 192 (20), 191 (80),
MS
1-Bromo-2-methyl-1,2-dihydro-3H-2-benzazepin-3-one (9 p): Treat-
ment of 6p (66 mg, 0.26 mmol, base, 30 min) according to the gen-
eral procedure, after purification (cyclohexane/ethyl acetate, 1:1),
165 (28), 115 (10).
220.0880.
HRMS (C16H12O): calcd. 220.0888; found
˜
IR (CCl4): ν
afforded 9 p (20 mg, 30%) as a pale brown oil.
Methyl{[2 (3 -phenylprop-1 -ynyl)phenyl]methylene}amine N-Ox-
ide (12): Treatment of 11 (180 mg, 0.78 mmol, 6 h) according to 1000 cm
2995, 2940, 1645 (C O), 1615, 1445, 1395, 1330, 1250, 1225, 1080,
1
.
1H NMR (250 MHz): δ 3.47 (br. s, 3 H, NCH3),
3
the general procedure, after purification (cyclohexane/ethyl acetate,
3:1), gave 12 (165 mg, 85%) as a reddish brown oil. IR (CCl4):
5.30 (s, 1 H, 1-H), 6.41 (d, J5,4
12.2 Hz, 1 H, 4-H), 7.02 (d,
MS
3J4,5
12.2 Hz, 1 H, 5-H), 7.33 7.51 (m, 4 H, Ar-H).
1
˜
ν
3065, 3030, 2950, 1575, 1495, 1455, 1420, 1290, 1175 cm
.
(70 eV; EI): m/z (%)
188 (45), 173 (69), 172 (100) [M
Br] ,
1H NMR (250 MHz): δ
3.82 (s, 3 H, NCH3), 3.89 (s, 2 H, 3 - 144 (74), 103 (47).
H), 7.24 7.45 (m, 7 H, Ar-H), 7.47 7.52 (m, 1 H, Ar-H), 7.93 (s,
1 H, 1-H) 9.22 (mc, 1 H, 6 -H). 13C NMR (125 MHz): δ 26.1
(C-3 ), 54.9 (NCH3), 80.2 (C-1 ), 94.2 (C-2 ), 122.7 (Ar-C), 126.9
(Ar-Cq), 127.5 (Ar-C), 128.0 (Ar-C), 128.4 (Ar-C), 128.8 (Ar-C),
129.8 (Ar-C), 131.3 (Ar-Cq), 132.2 (Ar-C), 133.4 (C-1), 136.5 (Ar-
3-[3 -(Trimethylsilyl)prop-2 -ynyl]furan-2-carbaldehyde (22): A solu-
tion of n-butyllithium in n-hexane (2.4 , 4.18 mL, 10.0 mmol) was
added dropwise at 78 °C under N2 to a solution of 21[37] (2.00 g,
9.13 mmol) in dry THF (50 mL). After this had stirred for 1 h at
78 °C, a solution of MgBr2 in diethyl ether (5 mL), freshly pre-
pared from Mg (292 mg, 12.0 mmol) and dibromoethane (1.88 g,
10.0 mmol), was added slowly. After 2 h, 1-bromo-3-(trimethylsilyl-
)prop-2-yne[32] (2.09 g, 10.1 mmol) was added, and the reaction
mixture was allowed to warm to room temp. and stirred for 1 h.
Cq).
MS (70 eV; EI): m/z (%)
249 (21) [M ], 232 (43), 158
(100) [M
CH2Ph] , 130 (90), 103 (23). HRMS (C17H15NO):
calcd. 249.1154; found 249.1152.
2-[2 -(3 -Bromoprop-2 -ynyl)phenyl]-1,3-dioxolane (4p): A solution
of 2d (2.00 g, 7.68 mmol) in acetone (50 mL) was treated with silver The solution was treated with a 1:1 mixture of satd. NH4Cl and
nitrate (91 mg, 0.54 mmol) and NBS[36] (1.64 g, 9.22 mmol) and
water and extracted with diethyl ether (3 30 mL). The combined
stirred at room temp. in the dark for 24 h. The reaction mixture organic phases were washed with brine, dried (MgSO4), and con-
was then cooled to 0 °C, diluted with cold water (30 mL) and ex-
tracted with diethyl ether (3 30 mL). The combined organic
phases were washed with brine, dried (MgSO4), and concentrated
in vacuo. Flash chromatography (SiO2; cyclohexane/ethyl acetate,
centrated in vacuo. Flash chromatography (SiO2; cyclohexane/ethyl
acetate, 30:1) afforded 1.31 g (58%) of a mixture containing the 3-
propargyl derivatives, together with small amounts of the 5-isomer.
Without separation of the regioisomers, liberation of the aldehyde
function according to the general procedure, after purification
(cyclohexane/ethyl acetate, 40:1), gave 22 (766 mg, 71%) as a yellow
˜
IR (CCl4): ν
40:1) afforded 4p (1.66 g, 81%) as a yellow oil.
2950, 2885, 1720, 1455, 1395, 1265, 1220, 1115, 1080, 1045 cm
1H NMR (250 MHz): δ 3.79 (s, 2 H, 1 -H), 4.09 (mc, 4 H, 4-
1
.
˜
oil. IR (CCl4): ν 2960, 2815, 2180 (CϵC), 1685 (C O), 1585,
1
H, 5-H), 5.97 (s, 1 H, 2-H), 7.30 (mc, 1 H, Ar-H), 7.36 (mc, 1 H, 1475, 1370, 1305, 1250, 1205 cm
.
1H NMR (250 MHz): δ
3
Ar-H), 7.49 7.57 (m, 2 H, Ar-H).
13C NMR (100 MHz): δ
0.16 (s, 9 H, SiMe3), 3.82 (s, 2 H, 1 -H), 6.68 (md, J4,5 1.2 Hz,
3
23.0 (C-1 ), 40.8 (C-3 ), 65.2 (C-4, C-5), 77.7 (C-2 ), 102.1 (C-2), 1 H, 4-H), 7.58 (d, J5,4 1.2 Hz, 1 H, 5-H), 9.82 (s, 1 H, CHO).
126.5 (Ar-C), 127.0 (Ar-C), 129.2 (Ar-C), 129.5 (Ar-C), 134.5 (Ar-
13C NMR (100 MHz): δ 0.0 (SiMe3), 16.9 (C-1 ), 87.0 (C-3 ),
Cq), 134.8 (Ar-Cq).
MS (70 eV; EI): m/z (%)
267 (5) [M
102.0 (C-2 ), 114.6 (C-4), 131.9 (C-3), 147.1 (C-5), 148.0 (C-2),
1, for 81Br], 265 (5) [M
1, for 79Br], 187 (55) [M
Br] , 115 178.9 (CHO).
MS (70 eV; EI): m/z (%)
206 (12) [M ], 191
(100), 73 (50).
264.9864; found 264.9865.
HRMS [M , for 79Br] (C12H11BrO2): calcd.
(100), 163 (9), 133 (7), 73 (30) [Si(CH3)3 ]. HRMS (C11H14O2Si):
calcd. 206.0763; found 206.0763.
2-(3 -Bromoprop-2 -ynyl)benzaldehyde (5p): Treatment of 4p
Methyl({3 -[3 -(trimethylsilyl)prop-2 -ynyl]furan-2 -yl}-
(200 mg, 0.75 mmol, 4 h) according to the general procedure, after methylene)amine N-Oxide (23): Treatment of 22 (285 mg,
purification (cyclohexane/ethyl acetate, 50:1), gave 5p (133 mg, 1.38 mmol, 4 h) according to the general procedure, after purifica-
Eur. J. Org. Chem. 2001, 3313 3332
3325

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
3
tion (cyclohexane/ethyl acetate, 1:1, 1:2), gave 23 (259 mg, 80%) as 7.9 Hz, 2 H, 3 -H), 2.74 (t, J4 ,3
7.9 Hz, 2 H, 4 -H), 3.50 (s, 2
˜
colourless crystals, m.p. 69 71 °C (decomp.).
IR (CCl4): ν
H, 3-H), 4.02 (mc, 4 H, 4 -H, 5 -H), 5.83 (s, 1 H, 2 -H),
7.11 7.25 (m, 3 H, Ar-H), 7.56 (mc, 1 H, Ar-H).
2960, 2895, 2175 (CϵC), 1715, 1600, 1490, 1415, 1250, 1205, 1050,
13C NMR
1
1010 cm
.
1H NMR (250 MHz): δ 0.14 (s, 9 H, SiMe3), 3.74 (100 MHz): δ 0.1 [Si(CH3)3], 18.4 (C-3), 19.3 (C-3 /4 ), 21.5 (C-
3
(s, 2 H, 1 -H), 3.83 (s, 3 H, NCH3), 6.82 (d, J4 ,5
1.8 Hz, 1 H, 3 /4 ), 65.5 (C-4 , C-5 ), 85.7 (C-1), 101.2 (C-2 ), 104.3 (C-2),
1.8 Hz, 1 H, 5 -H). 124.2 (Ar-C), 126.4 (Ar-C), 127.3 (Ar-C), 127.5 (Ar-C), 131.8 (Cq),
3
4 -H), 7.44 (s, 1 H, 1-H), 7.49 (d, J5 ,4
13C NMR (100 MHz): δ 0.1 (SiMe3), 17.1 (C-1 ), 53.5 (NCH3), 133.3 (Cq), 134.8 (Cq), 137.0 (Cq).
MS (70 eV; EI): m/z (%)
Si(CH3)3] , 201 (68), 129 (85), 73
C19H24O2Si (312.48): calcd. C 73.03, H 7.74;
86.0 (C-3 ), 103.5 (C-2 ), 113.9 (C-4 ), 124.7 (C-3 ), 125.9 (C-1), 312 (13) [M ], 239 (43) [M
141.7 (C-2 ), 143.9 (C-5 ). MS (70 eV; EI): m/z (%) 235 (20) (100) [Si(CH3)3 ].
[M ], 220 (61), 190 (19), 134 (60), 73 (100) [Si(CH3)3 ]. HRMS found C 73.17, H 7.76.
(C12H17NO2Si): calcd. 235.1029; found 235.1030.
2-[3 ,4 -Dihydro-1 -(prop-2 -ynyl)naphthalen-2 -yl]-1,3-dioxolane
7-Methyl-7,8-dihydrofuro[2,3-c]azepin-6-one (24): Treatment of 23 (27): A solution of 26 (8.31 g, 26.6 mmol) in dry methanol (150
(322 mg, 1.37 mmol; NaOMe, 4 h) according to the general proced-
ure, after purification (cyclohexane/ethyl acetate, 2:1), gave 24
(204 mg, 91%) as colourless crystals, m.p. 73 75 °C (ethanol).
mL) was treated with K2CO3 (3.68 g, 26.6 mmol) and stirred at
room temp. for 6 h. After ca. 100 mL of the solvent had been dis-
tilled off, water (100 mL) was added and the mixture was extracted
IR (CCl4): ν˜
1205, 1130, 1085 cm
2930, 2890, 1645 (C O), 1615, 1570, 1390, 1255, with diethyl ether (3 50 mL). The combined organic phases were
1
.
1H NMR (250 MHz): δ 3.05 (s, 3 H, washed with satd. aqueous NH4Cl and with brine, dried (MgSO4),
NCH3), 6.24 (d, 3J4,5 11.9 Hz, 1 H, 4-H), 6.40 (d, 3J6,7 2.1 Hz, and concentrated in vacuo. Flash chromatography (SiO2; cyclohex-
3
3
1 H, 6-H), 6.74 (d, J5,4
11.9 Hz, 1 H, 5-H), 7.30 (d, J7,6
ane/ethyl acetate, 30:1) afforded 27 (6.24 g, 98%) as colourless crys-
2.1 Hz, 1 H, 7-H). 13C NMR (100 MHz): δ 35.7 (NCH3), 44.3 tals, m.p. 60 °C (diethyl ether).
IR (CCl4): ν
3315 (ϵC H),
˜
(C-8), 108.9 (C-3), 119.0 (C-3a), 124.7 (C-4/5), 127.4 (C-4/5), 141.1
2945, 2890, 2830, 2115 (CϵC), 1445, 1385, 1235, 1185, 1095, 1005
1
4
(C-2), 149.4 (C-82), 166.5 (C-6). MS (70 eV; EI): m/z (%) 163 cm
.
1H NMR (250 MHz): δ
7.8 Hz, 2 H, 3 -H), 2.76 (t, 3J4 ,3
2.7 Hz, 2 H, 1 -H), 4.04 (mc, 4 H, 4-
H, 5-H), 5.84 (s, 1 H, 2-H), 7.11 7.29 (m, 3 H, Ar-H), 7.53 (mc, 1
H, Ar-H). 17.6 (C-1 ), 21.2 (C-3 /
13C NMR (100 MHz): δ
2.04 (t, J3
2.7 Hz, 1 H,
,1
(100) [M ], 135 (47), 134 (88) [M
NCH3] , 107 (26), 106 (26). 3 -H), 2.33 (t, 3J3 ,4
7.8 Hz,
HRMS (C9H9NO2): calcd. 163.0633; found 163.0638.
2 H, 4 -H), 3.49 (d, 4J1
,3
2-(1 -Bromo-3 ,4 -dihydronaphthalen-2 -yl)-1,3-dioxolane (25):
A
solution of 1-bromo-3,4-dihydronaphthalene-2-carbaldehyde[38]
(21.7 g, 91.4 mmol) in benzene (300 mL) was treated with ethylene
glycol (14.2 g, 0.23 mol) and PTSA (870 mg, 4.57 mmol) and
heated to reflux in a Dean Stark apparatus for 3 h. After cooling
to room temp., the mixture was washed with satd. aqueous
NaHCO3 and with brine. The organic phase was concentrated in
vacuo and the residue was purified by flash chromatography (SiO2,
cyclohexane/ethyl acetate, 30:1), affording 25 (24.6 g, 96%) as col-
4 ), 28.2 (C-3 /4 ), 65.5 (C-4, C-5), 69.3 (C-3 ), 81.9 (C-1 ), 101.1
(C-2), 123.9 (Ar-C), 126.5 (Ar-C), 127.4 (Ar-C), 127.6 (Ar-C), 131.6
(Cq), 133.5 (Cq), 134.4 (Cq), 136.9 (Cq).
MS (70 eV; EI): m/z
(%)
240 (76) [M ], 201 (97), 167 (100), 129 (99). C16H16O2
(240.30): calcd. C 79.97, H 6.71; found C 79.81, H 6.71.
2-[1 -(But-2 -ynyl)-3 ,4 -dihydronaphthalene-2 -yl]-1,3-dioxolane
(28): A solution of n-butyllithium in n-hexane (2.4 , 7.0 mL,
ourless solid, m.p. 56 °C (diethyl ether).
2885, 1625 (C C), 1480, 1380, 1250, 1180, 1090 cm
(250 MHz): δ 2.43 (t, 3J3 ,4 7.9 Hz, 2 H, 3 -H), 2.83 (t, 3J4 ,3
IR (CCl4): ν˜
2950, 16.8 mmol) was added at 78 °C under N2 to a solution of 27
1
.
1H NMR
(3.66 g, 14.2 mmol) in dry THF (75 mL). The mixture was stirred
for 2 h and a solution of methyl iodide (2.38 g, 16.8 mmol) in dry
7.9 Hz, 2 H, 4 -H), 4.04 (mc, 4 H, 4-H, 5-H), 5.99 (s, 1 H, 2-H), THF (5 mL) was added at 78 °C. The mixture was allowed to
7.08 7.13 (m, 1 H, Ar-H), 7.23 (mc, 2 H, Ar-H), 7.65 7.70 (m, 1 warm to room temp. and stirred for a further 3 h. A 1:1 mixture
H, Ar-H). 13C NMR (100 MHz): δ 23.6 (C-3 /4 ), 27.9 (C-3 / of satd. NH4Cl and water was added and the reaction mixture was
4 ), 65.7 (C-4, C-5), 104.3 (C-2), 126.7 (Ar-C), 127.1 (Ar-C), 127.6 extracted with diethyl ether (3
(Ar-C), 128.8 (Ar-C), 131.4 (Cq), 133.6 (Cq), 135.2 (Cq), 137.2 (Cq). phases were washed with brine, dried (MgSO4), and concentrated
282 (24) [M , for 81Br], 280 (23) in vacuo. Flash chromatography (SiO2; cyclohexane/ethyl acetate,
Br] , 129 (100). C13H13BrO2 30:1) afforded 28 (3.07 g, 79%) as a yellow oil. IR (CCl4): ν˜
2945, 2885, 2830, 1490, 1450, 1385, 1185, 1090, 1005 cm
30 mL). The combined organic
MS (70 eV; EI): m/z (%)
[M , for 79Br], 201 (45) [M
(281.15): calcd. C 55.54, H 4.66; found C 55.72, H 4.67.
1
.
1H
2.6 Hz, 3 H, 4 -H), 2.31
7.9 Hz, 2 H, 3 -H), 2.75 (t, 3J4 ,3
7.9 Hz, 2 H, 4 -H),
3.40 (mc, 2 H, 1 -H), 4.03 (mc, 4 H, 4-H, 5-H), 5.84 (s, 1 H, 2-H),
7.10 7.28 (m, 3 H, Ar-H), 7.55 (mc, 1 H, Ar-H).
13C NMR
5
NMR (250 MHz): δ
1.74 (t, J4
,1
{3-[2 -(1 ,3 -Dioxolan-2 -yl)-3 ,4 -dihydronaphthalen-1 -yl]prop-
1-ynyl}trimethylsilane (26): A solution of n-butyllithium in n-hex-
ane (2.4 , 6.50 mL, 15.7 mmol) was added dropwise at 78 °C
under N2 to a solution of 25 (4.00 g, 14.3 mmol) in dry THF (100
mL). After this had stirred for 2 h at 78 °C, a solution of MgBr2
in diethyl ether (15 mL), freshly prepared from Mg (540 mg,
22.2 mmol) and dibromoethane (3.20 mg, 17.1 mmol), was added
slowly and the reaction mixture was allowed to warm to room
temp. After 2 h, 1-bromo-3-(trimethylsilyl)prop-2-yne[32] (3.26 g,
17.1 mmol) was added and the solution was refluxed for 2 h. After
cooling to room temp., the solution was treated with a 1:1 mixture
of satd. NH4Cl and water and extracted with diethyl ether (3 60
mL). The combined organic phases were washed with brine, dried
(MgSO4), and concentrated in vacuo. Flash chromatography (SiO2;
cyclohexane/ethyl acetate, 40:1) afforded 26 (3.90 g, 88%) as a col-
(t, 3J3 ,4
(100 MHz): δ 3.8 (C-4 ), 17.9 (C-3 /4 ), 21.4 (C-3 /4 ), 28.3 (C-
1 ), 65.6 (C-3, C-4), 69.3 (C-2 /3 ), 76.6 (C-2 /3 ), 101.2 (C-2),
124.1 (Ar-C), 126.4 (Ar-C), 127.3 (Ar-C), 127.4 (Ar-C), 132.6 (Cq),
132.7 (Cq), 134.8 (Cq), 137.0 (Cq).
254 (12) [M ], 182 (59), 167 (90), 129 (100), 73 (69).
(C17H18O2): calcd. 254.1307; found 254.1305.
MS (70 eV; EI): m/z (%)
HRMS
3,4-Dihydro-1-(prop-2 -ynyl)naphthalene-2-carbaldehyde
(29a):
Treatment of 27 (1.78 g, 7.35 mmol, 1 h) according to the general
procedure, after purification (cyclohexane/ethyl acetate, 40:1), gave
29a (1.44 g, 99%) as a yellow oil. IR (CCl4): ν˜ 3310 (ϵC H),
2945, 2895, 2835, 2750, 2120 (CϵC), 1665 (C O), 1615, 1440,
1
1H NMR (250 MHz): δ 2.13 (t,
˜
ourless solid. M.p. 98 °C (diethyl ether). IR (CCl4): ν 2960, 1365, 1300, 1240, 1155 cm
.
1
2890, 2175 (CϵC), 1490, 1450, 1385, 1250, 1185, 1090, 1000 cm
.
4J3 ,1
H), 3.87 (d, J1 ,3
2.7 Hz, 1 H, 3 -H), 2.54 (mc, 2 H, 3-H), 2.77 (mc, 2 H, 4-
1H NMR (400 MHz): δ 0.10 (s, 9 H, SiMe3), 2.32 (t, J3 ,4
2.7 Hz, 2 H, 1 -H), 7.19 7.28 (m, 1 H, Ar-
3
4
3326
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
H), 7.32 (mc, 2 H, Ar-H), 7.67 7.75 (m, 1 H, Ar-H), 10.37 (s, 1 (CCl4): ν˜ 3015, 2930, 2855, 1675 (C O), 1590, 1480, 1375, 1305,
1
H, CHO).
13C NMR (100 MHz): δ
16.8 (C-1 ), 20.5 (C-3/4),
1275, 1200, 1060 cm
.
1H NMR (250 MHz): δ
2.55 (mt,
3
27.5 (C-3/4), 70.2 (C-3 ), 80.8 (C-2 ), 125.4 (Ar-C), 127.0 (Ar-C),
3J6,7
6.4 Hz, 2 H, 6-H), 2.93 (t, J7,6
6.4 Hz, 2 H, 7-H), 3.06
3
3
128.1 (Ar-C), 130.3 (Ar-C), 133.6 (Cq), 134.4 (Cq), 139.0 (Cq), 146.0 (d, J2,1 7.3 Hz, 2 H, 2-H), 3.11 (s, 3 H, NCH3), 6.19 (t, J1,2
(Cq), 190.2 (CHO).
177 (38), 167 (55), 152 (52), 128 (34). HRMS (C14H12O): calcd. Ar-H).
MS (70 eV; EI): m/z (%)
195 (100) [M ],
7.3 Hz, 1 H, 1-H), 7.08 7.23 (m, 3 H, Ar-H), 7.60 7.69 (m, 1 H,
13C NMR (125 MHz): δ
29.7 (C-6/7), 31.6 (C-6/7),
196.0888; found 196.0886.
35.3 (NCH3), 37.3 (C-2), 115.3 (Ar-C), 123.0 (C-1), 126.0 (Cq),
126.6 (Ar-C), 127.2 (Ar-C), 127.6 (Ar-C), 129.0 (C-5), 132.7 (Cq),
1-(But-2 -ynyl)-3,4-dihydronaphthalene-2-carbaldehyde (29b): Treat-
ment of 28 (1.01 g, 3.95 mmol, 5 h) according to the general pro-
cedure, after purification (cyclohexane/ethyl acetate, 40:1), gave 29b
(679 mg, 84%) as pale yellow crystals, m.p. 63 64 °C (diethyl
135.3 (Cq), 136.3 (Cq), 167.1 (C-3).
225 (60) [M ], 196 (100) [M NCH3] , 167 (12), 152 (12), 128
(14). C15H15NO (225.29): calcd. C 79.97, H 6.71, N 6.22; found
C 79.90, H 6.72, N 6.22. Compound 32a: Pale yellow oil. IR
(CCl4): ν˜ 3020, 2935, 2835, 1650 (C O), 1515, 1435, 1400, 1375,
MS (70 eV; EI): m/z (%)
ether).
1450, 1365, 1295, 1180 cm
5J4 ,1
2.6 Hz, 3 H, 4 -H), 2.48 2.58 (m, 2 H, 3/4-H), 2.71 2.80
(m, 2 H, 3/4-H), 3.79 (q, J1 ,4
(m, 2 H, Ar-H) 7.32 (mc, 1 H, Ar-H), 7.74 (mc, 1 H, Ar-H), 10.37
(s, 1 H, CHO). 3.7 (C-4 ), 17.1 (C-
13C NMR (100 MHz): δ
IR (CCl4): ν˜
2920, 2860, 1665 (C O), 1610, 1565,
.
1
1H NMR (250 MHz): δ 1.76 (t,
1
1305, 1195 cm
4 /5 -H), 2.52 (s, 3 H, 2-H), 2.78 2.88 (m, 2 H, 4 /5 -H), 3.80 (s, 3
H, NCH3), 6.59 (s, 1 H, 3 -H), 7.13 7.34 (m, 4 H, Ar-H).
13C
NMR (125 MHz): δ 20.7 (C-4 /5 ), 30.1 (C-2/4 /5 ), 31.0 (C-2/
.
1H NMR (250 MHz): δ 2.50 2.61 (m, 2 H,
5
2.6 Hz, 2 H, 1 -H), 7.18 7.25
4 /5 ), 37.2 (NCH3), 121.8 (Cq), 124.4 (Ar-C), 126.3 (Ar-C), 127.6
(Cq), 127.8 (Ar-C), 127.9 (Cq), 128.3 (Ar-C), 131.3 (Cq), 137.8 (C-
1 ), 20.3 (C-3/4), 27.5 (C-3/4), 75.7 (C-2 /3 ), 78.1 (C-2 /3 ),
125.6 (Ar-C), 126.9 (Ar-C), 128.0 (Ar-C), 130.2 (Ar-C), 134.0 (Cq),
139.0 (Cq), 147.5 (Cq), 190.6 (CHO). MS (70 eV; EI): m/z (%)
210 (43) [M ], 209 (76), 195 (100), 181 (20), 165 (63).
(210.27): calcd. C 85.68, H 6.71; found C 85.47, H 6.81.
3 ), 192.3 (C-1).
MS (70 eV; EI): m/z (%)
225 (93) [M ], 210
(100), 182 (20) [M COCH3] , 141 (24). HRMS (C15H15NO):
calcd. 225.1154; found 225.1155.
C15H14O
2,4-Dimethyl-2,4,6,7-tetrahydro-3H-naphtho[2,1-c]azepin-3-one
(31b) and 1-(2-Methyl-4,5-dihydro-2H-benzo[c]isoindol-1-yl)propan-
1-one (32b): Treatment of 30b (86 mg, 0.36 mmol, 1 equiv. NaOMe,
5 h) according to the general procedure, after purification (cyclo-
hexane/ethyl acetate, 3:1), gave 31b (55 mg, 64%) and 32b (15 mg,
Methyl{[3 ,4 -dihydro-1 -(prop-2 -ynyl)naphthalen-2 -yl]-
methylene}amine N-Oxide (30a): Treatment of 29a (1.54 g,
7.85 mmol, 7 h) according to the general procedure, after purifica-
tion (cyclohexane/ethyl acetate, 1:2), gave 30a (1.10 g, 62%) as beige
˜
IR (CCl4): ν
crystals, m.p. 108 109 °C (ethanol, decomp.).
18%).
Compound 31b: Pale yellow solid, m.p. 195 198 °C (eth-
3310 (ϵC H), 3020, 2945, 2890, 2830, 1545, 1420, 1250, 1195,
˜
anol). IR (CCl4): ν 2975, 2935, 1675 (C O), 1585, 1450, 1380,
1
1160, 1125 cm
.
1H NMR (250 MHz): δ
2.06 (t, 4J3
,1
1
1265, 1235, 1110, 1075 cm
.
1H NMR (250 MHz): δ 1.52 (d,
2.7 Hz, 1 H, 3 -H), 2.75 (mc, 2 H, 3 -H), 2.93 (mc, 2 H, 4 -H), 3.43
3JCH3,2 6.6 Hz, 3 H, 2-CH3), 2.42 2.54 (m, 1 H, 2-H), 2.56 2.72
4
(d, J1
2.7 Hz, 2 H, 1 -H), 3.83 (s, 3 H, NCH3), 7.13 7.29
,3
(m, 2 H, 6-H), 2.93 (mc, 2 H, 7-H), 3.13 (s, 3 H, NCH3), 5.87 (d,
(m, 3 H, Ar-H), 7.43 (s, 1 H, 1-H), 7.46 7.51 (m, 1 H, 8 -H).
13C NMR (100 MHz): δ 18.9 (C-1 ), 20.5 (C-3 /4 ), 28.1 (C-3 /
4 ), 54.4 (NCH3), 69.8 (C-3 ), 81.1 (C-2 ), 124.1 (Ar-C), 126.6
(Ar-C), 127.5 (Ar-C), 128.2 (Ar-C), 129.2 (Cq), 133.9 (Cq), 134.0
(Cq), 134.3 (C-1), 137.7 (Cq). MS (70 eV; EI): m/z (%) 225 (39)
3J1,2
5.8 Hz, 1 H, 1-H), 6.18 (d, 4J
1.5 Hz, 1 H, 5-H),
7.06 7.23 (m, 3 H, Ar-H), 7.60 7.68 (m, 1 H, Ar-H). 13C NMR
(125 MHz): δ 15.0 (2-CH3), 29.5 (C-6/7), 31.6 (C-6/7), 35.6 (C-
2), 39.6 (NCH3), 122.9 (Ar-C/C-1), 123.1 (Ar-C/C-1), 126.2 (Cq),
126.6 (Ar-C/C-5), 126.7 (Ar-C/C-5), 127.5 (Ar-C/C-5), 129.0 (Ar-
[M ], 196 (86), 182 (100), 167 (37), 152 (19), 115 (19).
(C15H15NO): calcd. 225.1154; found 225.1153.
HRMS
C/C-5), 132.7 (Cq), 133.6 (Cq), 136.3 (Cq), 169.1 (C-3).
MS
(70 eV; EI): m/z (%) 239 (61) [M ], 238 (100), 224 (16), 196 (97),
182 (15). HRMS (C16H17NO): calcd. 239.1310; found 239.1306.
{[ 1 - ( B u t -2 - y ny l) - 3 , 4 - d ihyd ro na ph t h al e n - 2 - yl ] -
methylene}methylamine N-Oxide (30b): Treatment of 29b (200 mg,
0.95 mmol, 6 h) according to the general procedure, after purifica-
tion (ethyl acetate/methanol, 10:1), gave 30b (142 mg, 62%) as beige
˜
Compound 32b: Pale yellow oil.
IR (CCl4): ν
3065, 2935,
1
2835, 1650 (C O), 1515, 1435, 1375, 1305, 1185, 1145 cm
.
1H
3
NMR (250 MHz): δ
1.19 (t, J3,2
7.5 Hz, 3 H, 3-H), 2.85 (q,
3J2,3 7.5 Hz, 2 H, 2-H), 3.75 (s, 3 H, NCH3), 6.58 (s, 1 H, 3 -H),
7.14 7.21 (m, 4 H, Ar-H). MS (70 eV; EI): m/z (%) 239 (26)
[M ], 210 (68), 182 (100), 167 (41). HRMS (C16H17NO): calcd.
239.1310; found 239.1311.
crystals, m.p. 136 137 °C (acetone, decomp.).
3025, 2940, 2890, 2830, 1670, 1545, 1415, 1175, 1155 cm
NMR (250 MHz): δ 2.6 Hz, 3 H, 4 -H),
1.75 (t, 5J4
2.69 2.79 (m, 2 H, 3 /4 -H), 2.90 3.00 (m, 2 H, 3 /4 -H), 3.35 (q,
5J1
2.6 Hz, 2 H, 1 -H), 3.82 (s, 3 H, NCH3), 7.12 7.28 (m,
3 H, Ar-H), 7.44 (s, 1 H, 1-H), 7.48 7.53 (m, 1 H, Ar-H).
13C
IR (CCl4): ν˜
1
.
1H
,1
,4
1-Bromo-7-fluoro-3,4-dihydronaphthalene-2-carbaldehyde
(35b):
PBr3 (1.01 g, 3.72 mmol) was added at 0 °C to a solution of DMF
(268 mg, 3.66 mmol) in dry CHCl3 (5 mL). After this had stirred
for 1.5 h, a solution of 34b[39] (200 mg, 1.22 mmol) in dry CHCl3
(5 mL) was added. The reaction mixture was allowed to warm to
room temp. (1 h) and was then heated to 50 °C for 1.5 h. After
cooling to room temp., the solution was poured into a cold 1:1
mixture of satd. NaHCO3 and water, neutralized with solid
NMR (100 MHz): δ 3.7 (C-4 ), 19.2 (C-1 ), 23.3 (C-3 /4 ), 28.2
(C-3 /4 ), 54.3 (NCH3), 75.8 (C-2 /3 ), 77.1 (C-2 /3 ), 124.3 (Ar-
C), 126.6 (Ar-C), 127.4 (Ar-C), 128.1 (Ar-C), 128.7 (Cq), 134.3
(Cq), 134.5 (C-1), 135.3 (Cq), 137.8 (Cq).
MS (70 eV; EI): m/z
(%) 239 (36) [M ], 196 (100), 186 (96), 167 (41), 165 (51).
C16H17NO (239.32): calcd. C 80.20, H 7.16, N 5.85; found C 80.05,
H 7.31, N 5.93.
NaHCO3, and extracted with chloroform (4
(31a) bined organic phases were washed with brine, dried (MgSO4) and
and 1-(2 -Methyl-4 ,5 -dihydro-2 H-benzo[e]isoindol-1 -yl)ethan-1- concentrated in vacuo. Flash chromatography (SiO2; cyclohexane/
10 mL). The com-
4-Methyl-2,4,6,7-tetrahydro-3H-naphtho[2,1-c]azepin-3-one
one (32a): Treatment of 30a (100 mg, 0.44 mmol; KOH, 1.5 h) ac-
cording to the general procedure, after purification (cyclohexane/
ethyl acetate, 2:1), gave 31a (62 mg, 62%) and 32a (17 mg, 17%).
Compound 31a: Colourless solid, m.p. 145 146 °C (ethanol). IR cm
ethyl acetate, 40:1) gave 35b (183 mg, 59%) as a yellow solid.
˜
M.p. 55 56 °C (diethyl ether). IR (CCl4): ν 2945, 2900, 2860,
1670 (C O), 1565, 1485, 1435, 1350, 1270, 1240, 1180, 1145, 1100
1
.
1H NMR (250 MHz): δ 2.62 (mc, 2 H, 3-H), 2.81 (mc,
Eur. J. Org. Chem. 2001, 3313 3332
3327

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
2 H, 4-H), 7.05 (mc, 1 H, Ar-H), 7.18 (mc, 1 H, Ar-H), 7.62 (mc, 1
was filtered and the solution was concentrated in vacuo. Purifica-
tion by flash chromatography (SiO2; cyclohexane/ethyl acetate,
24.8 Hz, C-6/8), 117.8 (d, 100:1) gave 36b (416 mg, 75%) as a yellow viscous oil. IR (CCl4):
H, Ar-H), 10.24 (s, 1 H, CHO). 13C NMR (125 MHz): δ 23.1
2
(C-3/4), 26.4 (C-3/4), 115.7 (d, J6,F
3
2J8,F
21.5 Hz, C-6/8), 129.0 (d, J5,F
7.9 Hz, C-5), 134.5 (d, ν˜ 3035, 2945, 2840, 2215 (CϵC), 1670 (C O), 1565, 1495, 1365,
3
1
4J4a,F
3.0 Hz, C-4a), 134.9 (d, J8a,F
8.2 Hz, C-8a), 135.4 (C- 1305, 1265, 1195 cm
.
1H NMR (250 MHz): δ
2.52 2.63
1
2), 137.3 (d, 4J1,F 2.4 Hz, C-1), 161.8 (d, J7,F 244.6 Hz, C-7), (m, 2 H, 3-H), 2.71 2.83 (m, 2 H, 4-H), 3.97 (s, 2 H, 3 -H), 7.01
193.0 (CHO). MS (70 eV; EI): m/z (%) 256 (27) [M , for 81Br], (mc, 1 H, Ar-H), 7.10 7.19 (m, 1 H, Ar-H), 7.23 7.43 (m, 5 H,
254 (27) [M , for 79Br], 175 (15) [M
144 (100).
C 51.60, H 3.13.
Br] , 147 (74), 146 (100), Ar-H), 7.53 (mc, 1 H, Ar-H), 10.39 (s, 1 H, CHO).
13C NMR
C11H8BrFO (255.08): calcd. C 51.79, H 3.16; found (100 MHz): δ 20.1 (C-3/4), 26.1 (C-3/4), 26.2 (C-3 ), 76.0 (C-2 ),
100.7 (C-1 ), 114.1 (d, 2J 23.3 Hz, C-6/8), 117.1 (d, 2J 21.8 Hz,
3
C-6/8), 127.2 (Ar-C), 128.0 (Ar-C), 128.9 (Ar-C), 129.1 (d, J5,F
9-Bromo-6,7-dihydro-5H-benzo[a]cycloheptene-8-carbaldehyde
(35c): PBr3 (4.22 g, 15.6 mmol) was added at 0 °C to a solution of
DMF (1.37 g, 18.7 mmol) in dry CHCl3 (10 mL). After this had
stirred for 1.5 h, a solution of 34c (1.00 g, 6.24 mmol) in dry CHCl3
(5 mL) was added. The reaction mixture was allowed to warm to
room temp. (1 h) and then refluxed for 3 h. After cooling to room
temp., the solution was poured into a cold 1:1 mixture of satd.
NaHCO3 and water, neutralized with solid NaHCO3 and extracted
4
3
7.3 Hz, C-5), 132.2 (d, J4a,F
2.9 Hz, C-4a), 134.4 (d, J8a,F
1
7.3 Hz, C-8a), 135.3 (Cq), 135.7 (Cq), 141.1 (Cq), 161.8 (d, J7,F
244.1 Hz, C-7), 192.4 (CHO).
MS (70 eV; EI): m/z (%)
290
(68) [M ], 261 (23), 183 (54), 91 (100), 77 (21).
(C20H15FO): calcd. 290.1107; found 290.1107.
HRMS
6,7-Dihydro-9-(3 -phenylprop-1 -ynyl)-5H-benzo[a]cycloheptene-8-
carbaldehyde (36c): A degassed (Ar) solution of 35c (1.19 g,
with chloroform (4 10 mL). The combined organic phases were 4.74 mmol) in benzene (20 mL) was treated with PdCl2(PPh3)2
washed with brine, dried (MgSO4), and concentrated in vacuo.
Flash chromatography (SiO2; cyclohexane/ethyl acetate, 20:1) gave
(330 mg, 0.47 mmol), CuI (ca. 10 mg) and 3-phenylprop-1-yne[35]
(660 mg, 5.69 mmol) and stirred in a sealed tube for 15 min. After
35c (587 mg, 37%) as a colourless oil. IR (CCl4): ν˜ 2940, 2860, addition of dry Et3N (527 mg, 5.21 mmol), the suspension was
1
1675 (C O), 1600, 1580, 1565, 1445, 1250, 1150, 1020 cm
NMR (250 MHz): δ 2.06 2.27 (m, 4 H, 6-H, 7-H), 2.60 (t, 40 °C for 2 h. The dark red mixture was filtered and the solution
3J5,6 6.9 Hz, 2 H, 5-H), 7.23 (mc, 1 H, Ar-H), 7.36 (mc, 2 H, Ar-
was concentrated in vacuo. Purification by flash chromatography
H), 7.67 (mc, 1 H, Ar-H), 10.21 (s, 1 H, CHO).
13C NMR (SiO2; cyclohexane/ethyl acetate, 60:1) gave 36c (868 mg, 76%) as a
(125 MHz): δ 23.7 (C-6), 32.0 (C-5/7), 33.5 (C-5/7), 126.8 (Ar-
C), 128.9 (Ar-C), 129.8 (Ar-C), 130.6 (Ar-C), 138.6 (Cq), 139.3 (CϵC), 1675 (C O), 1600, 1560, 1450, 1360, 1270, 1180, 1020
.
1H stirred under argon at room temp. for 2 h and then maintained at
˜
yellow, viscous oil. IR (CCl4): ν 3065, 3030, 2940, 2860, 2215
1
(Cq), 139.4 (Cq), 140.5 (Cq), 192.7 (CHO).
(%)
MS (70 eV; EI): m/z cm
.
1H NMR (250 MHz): δ 2.10 2.27 (m, 4 H, 6-H, 7-H),
252 (35) [M , for 81Br], 250 (35) [M , for 79Br], 171 (82), 2.58 (t, J5,6
6.9 Hz, 2 H, 5-H), 3.90 (s, 2 H, 3 -H), 7.22 7.37
(m, 8 H, Ar-H), 7.60 7.68 (m, 1 H, Ar-H), 10.44 (s, 1 H, CHO).
13C NMR (100 MHz): δ
21.4 (C-6), 26.3 (C-5/7), 32.0 (C-5/
3
142 (85), 128 (89), 115 (91). HRMS (C12H11BrO) [M , for 79Br]:
calcd: 249.9993; found 249.9994.
7), 34.2 (C-3 ), 79.3 (C-1 ), 99.2 (C-2 ), 126.5 (Ar-C), 127.0 (Ar-C),
128.0 (Ar-C), 128.6 (Ar-C), 128.8 (Ar-C), 129.3 (Ar-C), 129.6 (Ar-
C), 135.9 (Cq), 138.6 (Cq), 140.9 (Cq), 141.0 (Cq), 145.0 (Cq), 192.3
3,4-Dihydro-1-(3 -phenylprop-1 -ynyl)naphthalene-2-carbaldehyde
(36a): A degassed (Ar) solution of 35a (2.00 g, 8.44 mmol) in ben-
zene (80 mL) was treated with PdCl2(PPh3)2 (296 mg, 0.42 mmol),
CuI (ca. 10 mg) and 3-phenylprop-1-yne[35] (1.08 g, 9.28 mmol).
After 15 min, K3CO3 (2.33 g, 16.9 mmol) was added, the mixture
was stirred for 8 h at room temp., dry Et3N (2 mL) was added, and
stirring was continued for a further 21 h. The reaction mixture was
(CHO).
MS (70 eV; EI): m/z (%)
286 (26) [M ], 195 (100),
165 (35), 91 (32).
286.1357.
HRMS (C21H18O): calcd. 286.1358; found
Methyl{[3 ,4 -dihydro-1 -(3 -phenylprop-1 -ynyl)naphthalen-2 -yl]-
filtered and the solution was concentrated in vacuo. Purification of methylene}amine N-Oxide (37a): Treatment of 36a (500 mg,
the brown residue by flash chromatography (SiO2; cyclohexane/
1.84 mmol, 6 h) according to the general procedure, after purifica-
ethyl acetate, 60:1) afforded 36a (1.25 g, 54%) as pale yellow crys-
tion (cyclohexane/ethyl acetate, 1:2), gave 37a (523 mg, 94%) as a
tals, m.p. 110 °C (diethyl ether).
IR (CCl4): ν˜
3030, 2945, yellow oil.
IR (CCl4): ν˜
3065, 3030, 2945, 2890, 1545, 1450,
1
2895, 2220 (CϵC), 1665 (C O), 1600, 1495, 1455, 1365, 1305, 1190
1420, 1195, 1175, 1145 cm
.
1H NMR (250 MHz): δ 2.78 (t,
1
3
3
cm
.
1H NMR (250 MHz): δ 2.59 (t, J3,4 8.0 Hz, 2 H, 3- 3J3 ,4
7.9 Hz, 2 H, 3 /4 -H), 3.22 (t, J3 ,4
7.9 Hz, 2 H, 3 /4 -
H), 2.82 (t, 3J4,3 8.0 Hz, 2 H, 4-H), 3.97 (s, 2 H, 3 -H), 7.16 7.27 H), 3.73 (s, 3 H, NCH3), 3.95 (s, 2 H, 3 -H), 7.10 7.16 (m, 1 H,
(m, 1 H, Ar-H), 7.24 7.44 (m, 7 H, Ar-H), 7.82 7.87 (m, 1 H, Ar-H), 7.22 (mc, 2 H, Ar-H), 7.27 7.45 (m, 5 H, Ar-H), 7.66 (mc,
Ar-H), 10.40 (s, 1 H, CHO). 13C NMR (100 MHz): δ 19.8 (C-
1 H, Ar-H), 7.74 (s, 1 H, 1-H). 13C NMR (125 MHz): δ 22.9
3/4), 26.2 (C-3/4/3 ), 26.8 (C-3/4/3 ), 76.4 (C-1 ), 100.2 (C-2 ), 126.9
(C-3 /4 ), 26.3 (C-3 /4 /3 ), 27.4 (C-3 /4 /3 ), 54.6 (NCH3), 78.7
(Ar-C), 127.0 (Ar-C), 127.3 (Ar-C), 127.9 (Ar-C), 130.6 (Ar-C), (C-1 ), 99.0 (C-2 ), 123.8 (Cq), 126.5 (Ar-C), 126.6 (Ar-C), 127.0
132.6 (Cq), 135.8 (Cq), 136.4 (Cq), 137.7 (Cq), 140.3 (Cq), 192.5 (Ar-C), 127.2 (Ar-C), 128.0 (Ar-C), 128.6 (Ar-C), 128.7 (Ar-C),
(CHO).
MS (70 eV; EI): m/z (%)
272 (100) [M ], 243 (32), 128.8 (Cq), 133.1 (Cq), 136.4 (Cq), 136.5 (Cq), 136.6 (C-1).
MS
165 (40), 91 (40).
C20H16O (272.34): calcd. C 88.20, H 5.92;
(70 eV; EI): m/z (%) 301 (18) [M ], 210 (100), 141 (21), 115 (11),
found C 88.30, H 5.81.
91 (7). HRMS (C21H19NO): calcd. 301.1467; found 301.1467.
7-Fluoro-3,4-dihydro-1-(3 -phenylprop-1 -ynyl)naphthalene-2-carb- {[7 -Fluoro-3 ,4 -dihydro-1 -(3 -phenylprop-1 -ynyl)naphthalen-2 -
aldehyde (36b):
A
degassed (Ar) solution of 35b (500 mg,
yl]methylene}methylamine N-Oxide (37b): Treatment of 36b
1.96 mmol) in benzene (20 mL) was treated with PdCl2(PPh3)2
(280 mg, 0.96 mmol, 9 h) according to the general procedure, after
(70 mg, 0.10 mmol), CuI (ca. 5 mg), and 3-phenylprop-1-yne[35] purification (cyclohexane/ethyl acetate, 1:2), gave 233 mg of 37b
˜
(250 mg, 2.16 mmol) and stirred in a sealed tube for 15 min K2CO3 (76%) as a yellow oil.
(524 mg, 3.92 mmol) was added and the suspension was stirred un- 1545, 1485, 1420, 1260, 1200, 1170, 1135, 1000 cm
der argon at ca. 50 °C for 3 h. After addition of 0.5 mL of Et3N, (400 MHz): δ 2.73 (t, 3J3 ,4 7.9 Hz, 2 H, 3 -H), 3.20 (t, 3J4 ,3
stirring was continued at room temp. for 4 h. The brown mixture 7.9 Hz, 2 H, 4 -H), 3.73 (s, 3 H, NCH3), 3.95 (s, 2 H, 3 -H), 6.90
IR (CCl4): ν
3025, 2945, 2890, 2830,
1
.
1H NMR
3328
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
(mc, 1 H, Ar-H), 7.07 (mc, 1 H, Ar-H), 7.28 (mc, 1 H, Ar-H), 262 (12), 242 (18).
7.33 743 (m, 5 H, Ar-H), 7.71 (s, 1 H, 1-H).
HRMS (C21H18FNO): calcd. 319.1372;
13C NMR found 319.1372.
(100 MHz): δ
23.1 (C-3 /4 ), 26.3 (C-3 /4 ), 26.6 (C-3 ), 54.7
4,6,7,8-Tetrahydro-4-methyl-2-phenylbenzo[3,4]cyclohepta[1,2-c]-
azepin-3(2H)-one (38c): Treatment of 37c (213 mg, 0.68 mmol;
KOH, 5 h) according to the general procedure, after purification
(cyclohexane/ethyl acetate, 10:1), gave 38c (135 mg, 63%) as colour-
(NCH3), 78.3 (C-2 ), 99.4 (C-1 ), 111.8 (d, 2J
23.3 Hz, C-6 /
8 ), 113.7 (d, 2J
20.3 Hz, C-6 /8 ), 127.0 (Ar-C), 128.0 (Ar-C),
3
4
128.1 (d, J5 ,F
7.3 Hz, C-5 ), 128.8 (Ar-C), 130.6 (d, J4 a,F
4.4 Hz, C-4 a), 133.5 (d, 3J8 a,F 7.7 Hz, C-8 a), 134.9 (C-1), 135.1
less crystals, m.p. 168 169 °C (ethanol).
IR (CCl4): ν˜
3065,
1
(Cq), 136.1 (Cq), 160.4 (d, J7 ,F
242.7 Hz, C-7 ).
MS (70 eV;
3030, 2940, 2855, 1675 (C O), 1450, 1375, 1295, 1265, 1155, 1085
EI): m/z (%) 319 (33) [M ], 302 (38), 228 (100) [M CH2Ph] ,
183 (23), 91 (47). HRMS (C21H18FNO): calcd. 319.1372; found
319.1372.
1
cm
.
1H NMR (250 MHz): δ
1.87 2.18 (m, 3 H, 7/8-H),
2.28 2.43 (m, 1 H, 7/8-H), 2.51 2.64 (m, 1 H, 6-Ha), 2.78 2.93
3
(m, 1 H, 6-Hb), 3.24 (s, 3 H, NCH3), 3.36 (d, J2,1 6.3 Hz, 1 H,
3
2-H), 5.94 (d, J1,2
6.3 Hz, 1 H, 1-H), 6.25 (s, 1 H, 5-H), 7.11
{[8 ,9 -Dihydro-5 -(3 -phenylprop-1 -ynyl)-7 H-benzo[a]cyclohept-
5 -en-6 -yl]methylene}methylamine N-Oxide (37c): Treatment of 36c
(1.16 g, 4.05 mmol, 6 h) according to the general procedure, after
purification (cyclohexane/ethyl acetate, 3:1, 1:1), gave 37c (911 mg,
72%) as a viscous, yellow oil.
2860, 1550, 1495, 1450, 1205, 1170, 1150, 1135 cm
(250 MHz): δ 2.14 (m, 2 H, 6 -H), 2.58 (mc, 4 H, 5 -H, 7 -H),
3.75 (s, 3 H, NCH3), 3.87 (s, 2 H, 3 -H), 7.18 7.41 (m, 8 H, Ar-
H), 7.53 7.60 (m, 1 H, Ar-H), 7.79 (s, 1 H, 1-H).
13C NMR
(125 MHz): δ 25.3 (C-6 ), 26.3 (C-5 /7 ), 32.0 (C-5 /7 ), 34.9 (C-
3 ), 54.4 (NCH3), 81.3 (C-3 ), 97.2 (C-2 ), 126.1 (Ar-C), 126.9
(Ar-C), 127.9 (Ar-C), 128.3 (Ar-C), 128.5 (Ar-C), 128.7 (Ar-C),
128.9 (Ar-C), 129.7 (Ar-Cq), 136.6 (Ar-Cq), 136.8 (C-1), 138.5 (Cq),
139.5 (Cq), 141.2 (Cq). MS (70 eV; EI): m/z (%) 315 (31) [M ],
(mc, 1 H, Ar-H), 7.21 (mc, 2 H, Ar-H), 7.29 7.44 (m, 6 H, Ar-H).
13C NMR (125 MHz): δ
29.3 (C-7), 31.0 (C-6/8), 31.6 (C-6/
8), 36.2 (NCH3), 52.6 (C-2), 125.1 (C-1), 126.8 (Ar-C), 127.2 (Ar-
C), 127.6 (Ar-C), 128.4 (Ar-C), 128.5 (Ar-C), 128.6 (Cq), 128.7 (Ar-
C), 129.1 (Ar-C), 129.7 (C-5), 137.3 (Cq), 138.4 (Cq), 139.0 (Cq),
IR (CCl4): ν˜
3060, 3025, 2945,
1
.
1H NMR
141.6 (Cq), 166.1 (C-3).
[M ], 314 (100), 286 (11) [M
CONCH3] , 236 (44), 210 (21).
MS (70 eV; EI): m/z (%)
315 (78)
NCH3] , 258 (15) [M
C22H21NO (315.41): calcd. C
83.78, H 6.71, N 4.44; found C 83.57, H 6.63, N 4.34.
4,5,6,7-Tetrahydro-4-methyl-2-phenyl-3H-naphtho[2,1-c]azepin-3-
one (39a): A solution of 38a (120 mg, 0.40 mmol) in toluene (35
mL) was refluxed for 2 h. After concentration in vacuo, separation
by flash chromatography (SiO2; cyclohexane/ethyl acetate, 5:1, 3:1)
afforded 39a (47 mg, 39%), together with 38a (72 mg, 60%). M.p.
244 (100) [M
(C22H21NO): calcd. 315.1623; found 315.1620.
CH2Ph] , 196 (17), 115 (16), 91 (31).
HRMS
˜
179 180 °C (ethanol).
1645 (C O), 1490, 1440, 1395, 1225, 1005 cm
(250 MHz): δ 2.60 2.70 (m, 2 H, 6-H), 2.87 (t, J7,6
IR (CCl4): ν
3060, 3025, 2935, 2885,
1
.
1H NMR
7.9 Hz,
2,4,6,7-Tetrahydro-4-methyl-2-phenyl-3H-naphtho[2,1-c]azepin-3-
one (38a): Treatment of 37a (100 mg, 0.33 mmol; NaOMe, 3 h) ac-
cording to the general procedure, after purification (cyclohexane/
ethyl acetate, 1:1), gave 38a (78 mg, 78%) as colourless crystals,
m.p. 180 181 °C (ethanol).
1680 (C O), 1455, 1375, 1305, 1260, 1105 cm
(250 MHz): δ 2.46 2.74 (m, 2 H, 6-H), 2.91 3.06 (m, 2 H, 7-
H), 3.18 (s, 3 H, NCH3), 2.89 (d, J2,1
3
2 H, 7-H), 3.13 (s, 3 H, NCH3), 3.96 (br. s, 2 H, 5-H), 7.13 7.44
(m, 8 H, Ar-H, 1-H), 7.65 7.72 (m, 2 H, Ar-H).
13C NMR
(100 MHz): δ 28.2 (C-6/7), 29.5 (C-6/7), 35.3 (NCH3), 53.6 (C-
5), 124.4 (Ar-C), 127.0 (Ar-C), 127.6 (Ar-C), 127.7 (Ar-C), 128.0
(Ar-C), 128.1 (Ar-C), 128.4 (Ar-C), 129.1 (C-1), 132.9 (Cq), 133.8
(Cq), 135.2 (Cq), 138.6 (Cq), 138.9 (Cq), 141.3 (Cq), 167.5 (C-3).
MS (70 eV; EI): m/z (%) 301 (100) [M ], 272 (31) [M NCH3] ,
˜
IR (CCl4): ν
3065, 3030, 2940,
1
.
1H NMR
3
6.4 Hz, 1 H, 2-H), 6.26
6.4 Hz, 1 H, 1-H), 7.09 7.21 (m, 3
3
(s, 1 H, 5-H), 6.32 (d, J1,2
244 (28) [M
CONCH3] , 224 (12), 184 (34).
C21H19NO
H, Ar-H), 7.28 7.39 (m, 1 H, Ar-H), 7.41 (mc, 4 H, Ar-H),
7.62 7.70 (m, 1 H, Ar-H). 13C NMR (100 MHz): δ 29.6 (C-
6/7), 31.7 (C-6/7), 36.0 (NCH3), 52.2 (C-2), 121.7 (C-1), 123.1 (Ar-
C), 126.2 (Cq), 126.7 (Ar-C), 127.1 (Ar-C/C-5), 127.2 (Ar-C/C-5),
127.7 (Ar-C/C-5), 128.4 (Ar-C), 129.0 (Ar-C), 129.6 (Ar-C/C-5),
132.6 (Cq), 134.2 (Cq), 136.5 (Cq). 138.4 (Cq), 166.7 (C-3).
(70 eV; EI): m/z (%) 301 (100) [M ], 286 (16), 272 (12) [M
NCH3] , 244 (11), 224 (22), 196 (43). C21H19NO (301.38): calcd.
C 83.69, H 6.35, N 4.65; found C 83.51, H 6.44, N 4.50.
(301.38): calcd. C 83.69, H 6.35, N 4.65; found C 83.48, H 6.17,
N 4.48.
10-Fluoro-4,5,6,7-tetrahydro-4-methyl-2-phenyl-3H-naphtho[2,1-c]-
azepin-3-one (39b): A solution of 38b (50 mg, 0.16 mmol) in toluene
(15 mL) was refluxed for 2 h. After concentration in vacuo, separa-
tion by flash chromatography (SiO2; cyclohexane/ethyl acetate, 3:1)
afforded 39b (11 mg, 22%), together with 38b (17 mg, 34%). M.p.
MS
˜
168 170 °C (ethanol).
IR (CCl4): ν
3025, 2930, 2890, 1645
1
(C O), 1495, 1440, 1395, 1265, 1225, 1165, 1005 cm
.
1H
10-Fluoro-2,4,6,7-tetrahydro-4-methyl-2-phenyl-3H-naphtho[2,1-c]-
azepin-3-one (38b): Treatment of 37a (52 mg, 0.16 mmol; NaOMe,
2 h) according to the general procedure, after purification (cyclo-
hexane/ethyl acetate, 20:1), gave 38a (47 mg, 90%) as yellow crys-
3
NMR (250 MHz): δ
2.63 (t, J6,7
7.8 Hz, 2 H, 6-H), 2.83 (t,
3J7,6 7.8 Hz, 2 H, 7-H), 3.14 (s, 3 H, NCH3), 3.97 (br. s, 2 H, 5-
H), 6.89 (mc, 1 H, Ar-H), 7.00 (mc, 1 H, Ar-H), 7.07 (s, 1 H, 1-H),
7.12 (mc, 1 H, Ar-H), 7.29 7.45 (m, 3 H, Ar-H), 7.65 7.71 (m, 2
H, Ar-H). 13C NMR (100 MHz): δ 27.4 (C-6/7), 29.7 (C-6/7),
35.3 (C-5), 53.5 (NCH3), 111.4 (d, 2J 23.0 Hz, C-9/11), 113.9 (d,
˜
tals, m.p. 143 145 °C (ethanol).
IR (CCl4): ν
3025, 2935,
1
1680 (C O), 1575, 1490, 1450, 1375, 1305, 1265, 1185, 1100 cm
.
1H NMR (250 MHz): δ 2.46 2.72 (m, 2 H, 6-H), 2.88 2.97
2J
21.2 Hz, C-9/11), 128.1 (Ar-C), 128.2 (Ar-C), 128.3 (Ar-C),
3
(m, 2 H, 7-H), 3.19 (s, 3 H, NCH3), 3.87 (d, J2,1
2-H), 6.25 (d, J1,2
6.3 Hz, 1 H,
128.5 (Ar-C), 128.8 (d, 3J8,F 7.9 Hz, C-8), 130.6 (d, 4J 3.3 Hz,
3
6.3 Hz, 1 H, 1-H), 6.29 (s, 1 H, 5-H), 6.86
C-7a/11b), 132.3 (d, 4J
2.1 Hz, C-7a/11b), 135.5 (d, J11a,F
3
(mc, 1 H, Ar-H), 7.08 (mc, 1 H, Ar-H), 7.28 7.44 (m, 7 H, Ar-H).
7.6 Hz, C-11a), 138.7 (Cq), 139.8 (Cq), 141.8 (Cq), 162.0 (d, 1J10,F
13C NMR (100 MHz): δ
29.6 (C-6/7), 30.9 (C-6/7), 36.1
243.7 Hz, C-10), 167.3 (C-3).
MS (70 eV; EI): m/z (%)
319
(NCH3), 52.2 (C-2), 108.2 (d, 2J 23.3 Hz, C-9/11), 113.4 (d, 2J
20.4 Hz, C-9/11), 121.3 (C-1), 124.1 (Cq), 126.0 (Ar-C), 126.1 (C-
1), 127.1 (Ar-C), 128.2 (Ar-C), 129.1 (d, 3J8,F 7.3 Hz, C-8), 130.8
(100) [M ], 290 (24) [M
242 (15), 214 (35).
found 319.1372.
NCH3] , 262 (22) [M
HRMS (C21H18FNO): calcd. 319.1372;
CONCH3] ,
4
3
(d, J7a,F
2.9 Hz, C-7a), 132.2 (Cq), 133.1 (d, J11a,F
7.3 Hz,
C-11a), 136.7 (Cq), 160.5 (d, 1J10,F 242.7 Hz, C-10), 165.3 (C-3). 5,6,7,8-Tetrahydro-4-methyl-2-phenylbenzo[3,4]cyclohepta[1,2-c]-
MS (70 eV; EI): m/z (%)
319 (100) [M ], 304 (12), 290 (22),
azepin-3(2H)-one (39c): A solution of 38c (244 mg, 0.77 mmol) in
Eur. J. Org. Chem. 2001, 3313 3332
3329

K. Knobloch, M. Keller, W. Eberbach
FULL PAPER
toluene (50 mL) was refluxed for 2 h. After concentration in vacuo,
separation by flash chromatography (SiO2; cyclohexane/ethyl acet-
ate, 10:1, 3:1) afforded 39c (48 mg, 20%), together with 38c
2970, 2820, 1490, 1465, 1450, 1390, 1360, 1265, 1200, 1105, 1060
1
cm
.
1H NMR (250 MHz): δ
1.17 (s, 9 H, CH3), 3.64 (s, 2
3
3
H, 1-H), 3.64 (mc, 2 H, 3-H), 5.84 (td, J4,5
12.2 Hz, J4,3
3
4
(194 mg, 80%).
M.p. 135 138 °C (diethyl ether).
IR (CCl4): 4.0 Hz, 1 H, 4-H), 6.46 (td, J5,4
12.2 Hz, J5,3
2.1 Hz, 1 H,
ν
3060, 3020, 2930, 2855, 1640 (C O), 1450, 1425, 1395, 1095 5-H), 7.06 7.13 (m, 3 H, Ar-H), 7.14 7.20 (m, 1 H Ar-H). 13C
˜
cm
1
.
1H NMR (250 MHz): δ 2.17 2.28 (m, 4 H, 6-H. 7-H), NMR (100 MHz): δ 26.7 (CH3), 53.9 (Cq), 54.4 (C-1, C-3), 126.8
(Ar-C/C-4/5), 126.9 (Ar-C/C-4/5), 127.3 (Ar-C/C-4/5), 128.3 (Ar-
H), 6.94 (s, 1 H, 1-H), 7.17 7.40 (m, 7 H, Ar-H), 7.57 7.64 (m, 2 Cq), 130.2 (Ar-C/C-4/5), 132.3 (Ar-C/C-4/5), 136.5 (Ar-Cq). MS
H, Ar-H). 13C NMR (100 MHz): δ 32.0 (C-6/7/8), 32.1 (C-6/ (70 eV; EI): m/z (%)
201 (15) [M ], 186 (100), 144 (32) [M
7/8), 34.5 (C-6/7/8), 34.9 (NCH3), 54.6 (C-5), 126.5 (Ar-C), 127.7 C(CH3)3] , 130 (11) [M NC(CH3)3] . HRMS (C14H19N):
2.52 2.61 (m, 2 H, 8-H), 3.19 (s, 3 H, NCH3), 4.00 (br. s, 2 H, 5-
(Ar-C), 127.9 (Ar-C), 128.1 (Ar-C), 128.3 (Ar-C), 128.4 (Ar-C), calcd. 201.1517; found 201.1517.
128.5 (Cq), 129.0 (Ar-C), 132.6 (C-1), 137.2 (Cq), 139.1 (Cq), 140.4
2,3-Dihydro-2,4-dimethyl-1H-2-benzazepine (40f): A solution of 9f
(85 mg, 5.34 mmol) in dry diethyl ether (8 mL) was treated with
LAH (70 mg, 1.83 mmol) and stirred for 2 h at room temp. The
reaction mixture was poured into a 1:1 mixture of satd. NH4Cl and
(Cq), 140.5 (Cq), 140.6 (Cq), 167.1 (C-3).
MS (70 eV; EI): m/z
(%)
315 (100) [M ], 287 (16) [M
NCH3] , 258 (14) [M
CONCH3] , 236 (36).
found 315.1621.
HRMS (C22H21NO): calcd. 315.1623;
water and extracted with CH2Cl2 (3
ganic phases were washed with brine, dried (MgSO4) and concen-
tion of bromine in CCl4 (0.5 , 0.86 mL, 0.43 mmol) was added at trated in vacuo. Flash chromatography (SiO2; ethyl acetate) af-
0 °C to a solution of 9d (106 mg, 0.43 mmol) in CH2Cl2 (2 mL). forded 40f (74 mg, 95%) as a pale yellow oil. IR (CCl4): ν˜
10 mL) The combined or-
4-Bromo-1,2-dihydro-2-methyl-3H-2-benzazepin-3-one (9p): A solu-
1
The reaction mixture was allowed to warm to room temp. and
3015, 2930, 1715, 1490, 1440, 1365, 1140, 1050 cm
.
1H NMR
stirred for 24 h. The resulting pale yellow solution was treated with (250 MHz): δ 1.80 (d, 4JCH3,5 1.3 Hz, 3 H, CH3), 2.32 (s, 3 H,
satd. aqueous NaS2O3 (10 mL) and extracted with CH2Cl2 (3 10 NCH3), 3.35 (s, 2 H, 1/3-H), 3.72 (s, 2 H, 1/3-H), 6.24 (q, 4J5,CH3
mL). The combined organic phases were washed with brine, dried
(MgSO4) and concentrated in vacuo. Flash chromatography (SiO2;
1.3 Hz, 1 H, 5-H) 6.95 7.21 (m, 4 H, Ar-H).
(100 MHz): δ 24.4 (CH3), 43.2 (NCH3), 60.9 (C-1/3), 63.7 (C-1/
13C NMR
cyclohexane/ethyl acetate, 2:1) gave 9p (86 mg, 79%) as colourless 3), 126.3 (C-5/Ar-C), 126.5 (C-5/Ar-C), 127.2 (C-5/Ar-C), 128.8 (C-
˜
crystals, m.p. 150 °C (ethanol). IR (CCl4): ν 2925, 1655 (C
5/Ar-C), 130.0 (C-5/Ar-C), 136.5 (Cq), 137.5 (Cq), 138.7 (Cq).
1H NMR MS (70 eV; EI): m/z (%) 173 (77) [M ], 158 (100), 144 (73), 128
3.13 (br. s, 3 H, NCH3), 4.25 (s, 2 H, 1-H), (65), 115 (65). HRMS (C12H15N): calcd. 173.1204; found
7.28 7.43 (m, 4 H, Ar-H), 7.66 (s, 1 H, 5-H).
13C NMR 173.1204.
1
O), 1555, 1445, 1395, 1265, 1205, 1115, 1000 cm
(250 MHz): δ
.
(100 MHz): δ 35.7 (NCH3), 53.3 (C-1), 121.6 (Cq), 127.3 (Ar-C),
128.8 (Ar-C), 129.1 (Ar-C), 129.6 (Ar-C), 134.7 (Cq), 135.7 (Cq),
2,3-Dihydro-7,8-dimethoxy-2-methyl-4-(4 -methylphenyl)-1H-2-
benzazepine (40o): A solution of 9o (70 mg, 0.23 mmol) in dry di-
ethyl ether (8 mL) was treated with LAH (33 mg, 0.87 mmol) and
stirred for 5 h at room temp. The reaction mixture was poured into
a 1:1 mixture of satd. NH4Cl and water and extracted with CH2Cl2
138.2 (C-5), 162.4 (C-3).
MS (70 eV; EI): m/z (%)
253 (19)
[M , for 81Br] , 251 (19) [M , for 79Br], 172 (100) [M Br] , 143
(32), 115 (72). C11H10BrNO (252.11): calcd. C 52.41, H 4.00, N
5.56; found C 52.37, H 3.85, N 5.49.
(3
10 mL). The combined organic phases were washed with
2,3-Dihydro-2-methyl-1H-2-benzazepine (40a): A solution of 9a
brine, dried (MgSO4) and concentrated in vacuo. Flash chromato-
(50 mg, 1.83 mmol) in dry diethyl ether (10 mL) was treated with graphy (SiO2; ethyl acetate/methanol, 10:1) afforded 40o (43 mg,
˜
65%) as a pale yellow oil. IR (CCl4): ν 2930, 2835, 1710, 1510,
LAH (44 mg, 1.15 mmol) and stirred for 4 h at room temp. The
1
reaction mixture was poured into a 1:1 mixture of satd. NH4Cl and 1340, 1265, 1235, 1125 cm
.
1H NMR (250 MHz): δ 2.38 (s,
water and extracted with CH2Cl2 (3 10 mL). The combined or-
ganic phases were washed with brine, dried (MgSO4) and concen-
trated in vacuo. Flash chromatography (SiO2; ethyl acetate) af-
forded 40a (36 mg, 78%) as a colourless oil. IR (CCl4): ν˜ 3015,
3 H, 4 -CH3), 2.55 (s, 3 H, NCH3), 3.72 (s, 2 H, 1/3-H), 3.84 (s,
2 H, 1/3-H), 3.89 (s, 3 H, OCH3), 3.92 (s, 3 H, OCH3), 6.80 (s,
1 H, 6/9-H), 6.86 (s, 1 H, 6/9-H), 6.98 (s, 1 H, 5-H), 7.19 (md,
3Jo-Ar-H 8.0 Hz, 2 H, Ar-H), 7.41 (md, 3Jo-Ar-H 8.0 Hz, Ar-H).
2900, 2870, 2795, 1490, 1445, 1360, 1270, 1185, 1125, 1105, 1045
13C NMR (125 MHz): δ
22.4 (4 -CH3), 41.5 (NCH3), 56.0
1
cm
.
1H NMR (250 MHz): δ 2.41 (s, 3 H, NCH3), 3.54 (dd, (OCH3), 56.3 (C-1/3), 57.7 (C-1/3), 112.7 (C-6/9), 113.0 (C-6/9),
4
3J3,4
3.8 Hz, J3,5
2.1 Hz, 2 H, 3-H), 3.82 (s, 2 H, 1-H), 5.77
126.0 (Ar-C), 127.7 (Cq), 129.4 (Ar-C), 130.0 (C.5), 130.7 (Cq),
137.3 (Cq), 137.6 (Cq), 138.6 (Cq), 148.3 (C-7/8), 148.5 (C-7/8).
3
3
3
(td, J4,5
12.2 Hz, J4,3
3.8 Hz, 1 H, 4-H), 6.45 (td, J5,4
4
12.2 Hz, J5,3
2.1 Hz, 1 H, 5-H), 7.06 7.25 (m, 4 H, Ar-H).
MS (70 eV; EI): m/z (%)
309 (62) [M ], 218 (20), 204 (100), 91
13C NMR (100 MHz): δ
43.2 (NCH3), 60.1 (C-1/3), 61.4 (C-1/ (27). HRMS (C20H23NO2): calcd. 309.1729; found 309.1723.
3), 127.1 (Ar-C/C-4/5), 127.2 (Ar-C/C-4/5), 128.9 (Ar-C/C-4/5),
129.7 (Ar-C/C-4/5), 130.5 (Ar-C/C-4/5), 130.7 (Ar-C/C-4/5), 136.2
1,2,4,5-Tetrahydro-2-methyl-3H-2-benzazepin-3-one (41a): A solu-
tion of 9a (50 mg, 0.29 mmol) in methanol (20 mL) was treated
with 10% Pd/C (10 mg) and hydrogen (12 bar) for 4 h at room
temp. The reaction mixture was filtered (Kieselguhr) and concen-
trated in vacuo. Purification by flash chromatography (SiO2; cyclo-
hexane/ethyl acetate, 3:1) gave 41a (48 mg, 95%) as colourless crys-
(Ar-Cq), 138.2 (Ar-Cq).
MS (70 eV; EI): m/z (%)
159 (39)
[M ], 158 (100) [M
1], 144 (36), 115 (44). HRMS (C11H13N):
calcd. 159.1048; found 159.1048.
2-(tert-Butyl)-2,3-dihydro-1H-2-benzazepine (40c): A solution of 9c
˜
(70 mg, 0.33 mmol) in dry diethyl ether (10 mL) was treated with tals, m.p. 86 87 °C (ethanol). IR (CCl4): ν 3020, 2945, 2905,
1
LAH (50 mg, 1.32 mmol) and stirred for 3 h at room temp. The
reaction mixture was poured into a 1:1 mixture of satd. NH4Cl and (250 MHz): δ
water and extracted with CH2Cl2 (3 10 mL). The combined or-
ganic phases were washed with brine, dried (MgSO4) and concen-
trated in vacuo. Flash chromatography (SiO2; ethyl acetate) af-
1665 (C O), 1445, 1395, 1355, 1210, 1100, 1025 cm
.
1H NMR
3
2.92 (t, J4,5
NCH3), 3.17 (t, J4,5
6.8 Hz, 2 H, 4/5-H), 3.05 (s, 3 H,
3
6.8 Hz, 2 H, 4/5-H), 4.49 (s, 2 H, 1-H),
7.04 7.18 (m, 3 H, Ar-H), 7.20 7.26 (m, 1 H, Ar-H). 13C NMR
(125 MHz): δ
28.8 (C-4/5), 33.6 (C-4/5), 35.2 (NCH3), 54.5 (C-
˜
forded 40c (60 mg, 92%) as a colourless oil. IR (CCl4): ν 3015,
1), 126.0 (Ar-C), 128.2 (Ar-C), 128.8 (Ar-C), 130.5 (Ar-C), 134.3
3330
Eur. J. Org. Chem. 2001, 3313 3332

Synthesis of Annulated Azepin-3-one Derivatives
FULL PAPER
(Ar-Cq), 137.7 (Ar-Cq), 173.6 (C-3). MS (70 eV; EI): m/z (%)
[1]
[2]
[1a]
175 (36) [M ], 146 (17) [M NCH3] , 118 (46) [M CONCH3] ,
Reviews:
1,3-Dipolar Cycloaddition Chemistry, vol. 1 and 2
[1b]
117 (100).
C11H13NO (175.23): calcd. C 75.40, H 7.48, N 7.89;
(Ed.: A. Padwa), John Wiley & Sons, New York, 1984.
V. A. Bakulev, C. O. Kappe, A. Padwa, Organic Synthesis: The-
ory and Applications 1996, vol. 3, p. 149 229.
found C 75.27, H 7.20, N 8.04.
[2a]
[2b]
2-tert-Butyl-1,2,4,5-tetrahydro-3H-2-benzazepin-3-one (41c): A so-
lution of 9c (100 mg, 0.46 mmol) in methanol (20 mL) was treated
with 10% Pd/C (20 mg) and hydrogen (12 bar) for 4 h at room
temp. The reaction mixture was filtered (Kieselguhr) and concen-
trated in vacuo. Purification by flash chromatography (SiO2; cyclo-
hexane/ethyl acetate, 1:2) gave 41c (97 mg, 96%) as colourless crys-
Reviews:
G. Zecchi, Synthesis 1991, 181 188.
P. W.
Groundwater, M. Nyerges, Adv. Heterocycl. Chem. 1999, 73,
97 129.
[3] [3a]
W. Eberbach, J. Roser, Tetrahedron Lett. 1987, 28,
[3b]
2689 2692.
1989, 30, 5591 5594.
ron Lett. 1992, 31, 61 64.
W. Eberbach, W. Maier, Tetrahedron Lett.
[3c]
W. Eberbach, N. Laber, Tetrahed-
˜
tals, m.p. 90 91 °C (ethanol). IR (CCl4): ν 3020, 2975, 2915,
[4]
[5]
H. U. Reißig, Nachr. Chem. Tech. Lab. 1986, 34, 237 240.
For instance, 5-exo-methylene isoxazolidines, formed by cyclo-
addition of nitrones to allenes, are transformed into 3-pyrrolid-
inones by initial N O cleavage and subsequent N C rebond-
ing: A. Padwa, M. Matzinger, Y. Tomioka, M. K. Venkatram-
anan, J. Org. Chem. 1988, 53, 955 963.
J. Bussenius, N. Laber, T. Müller, W. Eberbach, Chem. Ber.
1994, 127, 247 259.
bach, Liebigs Ann. 1996, 1855 1866.
D. J. Pasto, Tetrahedron 1984, 40, 2805 2827.
H. Hopf, in: The Chemistry of Allenes (Ed.: S. R. Landor),
Academic Press, New York, 1982, vol. 2, p. 525 562.
W. Carruthers, in: Cycloaddition Reactions in Organic Syn-
thesis, Pergamon Press, Oxford, Weinheim, 1990.
Larock, in: Comprehensive Organic Transformations, Wiley-
VCH, 1999, p. 541. [9c] U. Koop, G. Handke, N. Krause, Liebigs
Ann. 1996, 1487 1499, and references.
For a recent review, see: G. Broggini, G. Zecchi, Gazz. Chim.
Ital. 1996, 126, 479 488.
H. Hopf, in: The Chemistry of Allenes (Ed.: S. R. Landor),
Academic Press, New York, 1982, vol. 2, p. 563 577.
K. Knobloch, Dissertation, Universität Freiburg, 2000.
For a preliminary communication, see: K. Knobloch, W. Eber-
bach, Org. Lett. 2000, 2, 1117 1120.
I. Z. Egenburg, Russ. Chem. Rev. 1978, 47, 470 485.
S. Nagashima, K. Kanematsu, Tetrahedron: Asymmetry
1990, 1, 743 749.
Bender, D. K. Moss, M. H. Nantz, J. Org. Chem. 1996, 61,
4014 4021. [15c] T. Choshi, T. Sada, H. Fujimoto, C. Nagay-
ama, E. Sugino, S. Hibino, J. Org. Chem. 1997, 62, 2535 2543.
M. Oku, S. Arai, K. Katayama, T. Shioiri, Synlett 2000,
493 494.
The ring transformation of type 7 Ǟ 8 can be brought about
either by thermal or by photochemical activation of 4-isoxazol-
P. Grünanger, P. Vita-Finzi, in: Heterocyclic Com-
pounds (Ed.: J. E. Dowling), Wiley, New York, 1999, vol. 49,
part 2, p. 575f and 696f.
1
1660 (C O), 1440, 1400, 1350, 1340, 1195, 1100 cm
.
1H NMR
(250 MHz): δ 1.42 (s, 9 H, CH3), 2.90 2.99 (m, 2 H, 4/5-H),
3.12 3.22 (m, 2 H, 4/5-H), 4.55 (s, 2 H, 1-H), 7.00 7.06 (m, 1 H,
Ar-H), 7.07 7.15 (m, 2 H, Ar-H), 7.17 7.25 (m, 1 H, Ar-H).
13C NMR (100 MHz): δ
29.1 (CH3), 29.2 (C-4/5), 36.5 (C-4/5),
48.4 (C-1), 57.6 (Cq), 125.9 (Ar-C), 127.7 (Ar-C), 128.2 (Ar-C),
130.6 (Ar-C), 136.0 (Ar-Cq), 137.6 (Ar-Cq), 175.2 (C-3). MS
(70 eV; EI): m/z (%) 217 (44) [M ], 160 (27) [M C(CH3)3] ,
118 (20) [M CONC(CH3)3] , 117 (100), 57 (20) [C(CH3)3 ].
[6] [6a]
[6b]
E. Lopez-Calle, J. Höfler, W. Eber-
[7]
[8]
HRMS: (C14H19NO): calcd. 217.1467; found 217.1466.
[9] [9a]
1,2,4,5-Tetrahydro-7,8-dimethoxy-2-methyl-3H-2-benzazepin-3-one
(41l): A solution of 9l (38 mg, 0.16 mmol) in methanol (15 mL)
was treated with 10% Pd/C (10 mg) and hydrogen (10 bar) for 4 h
at room temp. The reaction mixture was filtered (through kiesel-
guhr) and concentrated in vacuo. Purification by flash chromato-
graphy (SiO2; cyclohexane/ethyl acetate, 1:2) gave 41l (35 mg, 92%)
[9b]
R. C.
[10]
[11]
as a colourless oil.
O), 1520, 1465, 1395, 1345, 1260, 1205, 1110, 1010 cm
NMR (250 MHz): δ 2.87 2.96 (m, 2 H, 4/5-H), 3.03 3.15 (m,
IR (CCl4): ν˜
2935, 2905, 2850, 1665 (C
1
.
1H
[12]
[13]
2 H, 4/5-H), 3.06 (s, 3 H, NCH3), 3.85 (s, 3 H, OCH3), 3.87 (s, 3
H, OCH3), 4.43 (s, 2 H, 1-H), 6.58 (s, 1 H, Ar-H), 6.64 (s, 1 H, Ar-
[14]
H).
13C NMR (100 MHz): δ
28.5 (C-4/5), 33.5 (C-4/5), 35.3
[15] [15a]
(NCH3), 54.1 (C-1), 56.0 (OCH3), 56.1 (OCH3), 112.3 (Ar-C),
113.5 (Ar-C), 126.3 (C-5a/9a), 129.8 (C-5a/9a), 146.7 (C-7/8), 148.7
(C-7/8), 173.9 (C-3). MS (70 eV; EI): m/z (%) 235 (100) [M ],
[15b]
J. D. Spence, J. K. Wyatt, D. M.
220 (25), 178 (26), 162 (21).
235.1208; found 235.1208.
HRMS (C13H17NO3): calcd.
[15d]
[16]
1,2-Dihydro-2-methyl-3H-2-benzazepine-3-thione (42): A suspension
of P4S10 (156 mg, 0.35 mmol) and sodium carbonate (37 mg,
0.35 mmol) in THF (5 mL) was stirred for 30 min at room temp.,
treated with 9a (50 mg, 0.29 mmol) and heated to reflux for 13 h.
The yellow reaction mixture was concentrated in vacuo and the
crude material was purified by flash chromatography (SiO2; cyclo-
hexane/ethyl acetate, 2:1, 1:2) to afford 42 (36 mg, 65%) as yellow
[16a]
ines:
[16b]
E. Lopez-Calle, W. Eberbach,
J. Chem. Soc., Chem. Commun. 1994, 301 302.
[17]
The crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC-160786 (9a)
and -160787 (31a). Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [Fax: (internat.)
deposit@ccdc.cam.ac.uk].
crystals, together with 9a (17 mg, 34%).
M.p. 146 147 °C (di-
˜
ethyl ether). IR (CCl4): ν 3070, 3025, 2920, 1495, 1395, 1345,
1
1295, 1280, 1235, 1100 cm
.
1H NMR (250 MHz): δ 3.58 (s,
3
44-1223/336-033; E-mail:
3 H, NCH3), 4.50 (s, 2 H, 1-H), 6.84 (d, J4,5
11.9 Hz, 1 H, 4-
H), 7.08 (d, 3J5,4 11.9 Hz, 1 H, 5-H), 7.28 7.34 (m, 1 H, Ar-H),
[18] [18a]
7.38 7.46 (m, 3 H, Ar-H). 43.4
13C NMR (125 MHz): δ
W. Eberbach, J. Roser, Tetrahedron 1986, 42, 2221 2234.
[18b]
W. Maier, W. Eberbach, Helv. Chim. Acta 1991, 74,
(NCH3), 58.3 (C-1), 127.3 (C-4), 128.9 (Ar-C), 129.1 (Ar-C), 129.8
(Ar-C), 133.8 (Ar-Cq), 134.6 (C-5), 135.6 (Ar-Cq), 190.3 (C-3).
MS (70 eV; EI): m/z (%) 189 (100) [M ], 156 (27), 128 (43), 116
(13). HRMS (C11H11NS): calcd. 189.0612; found 189.0609.
1095 1101.
2063 2068.
K. Marx, W. Eberbach, Chem. Eur. J. 2000, 6,
[18c]
Y. Tan, T. Hartmann, V. Huch, H. Dürr, P.
Valat, V. Wintgens, J. Kossanyi, J. Org. Chem. 2001, 66,
1130 1137.
[19]
[20]
Reviews on cyclopropanones: [19a] N. J. Turro, Acc. Chem. Res.
[19b]
1969, 2, 25 32.
Turley, Top. Curr. Chem. 1974, 47, 73 156.
For a recent review on isoindoles, see: T. J. Donohoe, in: Sci-
ence of Synthesis, Houben-Weyl Methods of Molecular Trans-
formations (Ed.: E. J. Thomas), Thieme, Stuttgart, 2000, vol.
10, p. 653 692.
H. H. Wasserman, G. M. Clark, P. C.
Acknowledgments
Special thanks are due to Sabine Müller for her technical assist-
ance. Financial support of this work by the Fonds der Chemischen
Industrie is gratefully acknowledged.
Eur. J. Org. Chem. 2001, 3313 3332
3331

K. Knobloch, M. Keller, W. Eberbach
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