Simultaneous synthesis of 4,5-dihydro-3H-azepines and 3H-azepines, bearing alkoxy and alkylsulfanyl substituents, through metallation of 2-aza-1,3,5-trienes by t-BuOK

Article abstract of DOI:10.1016/j.jorganchem.2011.07.016

A new range of alkoxy- and alkylsulfanyl-substituted 4,5-dihydro-3H- azepines and 3H-azepines have simultaneously been obtained from conjugated 2-aza-1,3,5-trienes by treatment with t-BuOK under mild reaction conditions (THF/DMSO, ～-30 °C, 30 min). One-pot synthesis of 1-aza-1,3,4-trienes from α-lithiated alkoxyallenes, isopropyl isothiocyanate and alkyl iodides, followed by the thermally induced sigmatropic [1,5]-H shift, easily leads to starting 2-aza-1,3,5-trienes. The reaction proceeds via generation and [1,7]-electrocyclization of azatrienyl anions and represents a novel simple approach to both azacycloheptadienes and azacycloheptatrienes.

Full text of DOI:10.1016/j.jorganchem.2011.07.016

Journal of Organometallic Chemistry 696 (2011) 3359e3368
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Simultaneous synthesis of 4,5-dihydro-3H-azepines and 3H-azepines, bearing
alkoxy and alkylsulfanyl substituents, through metallation of 2-aza-1,3,5-trienes
by t-BuOK
*
Nina A. Nedolya , Ol’ga A. Tarasova, Ol’ga G. Volostnykh, Alexander I. Albanov, Boris A. Trofimov
A. E. Favorsky Irkutsk Institute of Chemistry of the Russian Academy of Sciences, Siberian Branch, Favorsky Street 1, 664033 Irkutsk, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 May 2011
Accepted 12 July 2011
A new range of alkoxy- and alkylsulfanyl-substituted 4,5-dihydro-3H-azepines and 3H-azepines have
simultaneously been obtained from conjugated 2-aza-1,3,5-trienes by treatment with t-BuOK under mild
ꢁ
reaction conditions (THF/DMSO, wꢀ30 C, 30 min). One-pot synthesis of 1-aza-1,3,4-trienes from
a-
lithiated alkoxyallenes, isopropyl isothiocyanate and alkyl iodides, followed by the thermally induced
sigmatropic [1,5]-H shift, easily leads to starting 2-aza-1,3,5-trienes. The reaction proceeds via generation
and [1,7]-electrocyclization of azatrienyl anions and represents a novel simple approach to both azacy-
cloheptadienes and azacycloheptatrienes.
Keywords:
4
3
,5-Dihydro-3H-azepines
H-Azepines
Azatrienes
Metallation
Ó 2011 Elsevier B.V. All rights reserved.
Hydrogen transfer
[1,7]-Electrocyclization
1. Introduction
from our own works [8], the reports on the synthesis of such aze-
pinic structures are still rare [9].
Azepines and their partly or fully reduced congeners are
found as constituents of the wide range of natural products and
pharmaceutically important compounds or their precursors
possessing psychotropic, antidepressant, anticonvulsant, anti-
cancer, antibacterial, anti-HIV, and other bioactivities [1]. In
particular, azepine-based drugs, such as Carbamazepine [2],
Insidon [3], Imipramine, and their analogues [4] are intensively
used for the treatment of trigeminal neuralgia, diverse forms of
epilepsy, schizophrenia, memory impairment, alcoholism, senile
dementia, Alzheimer’s disease, etc. [2e5]. It is worthy to note
that the interest in seven-membered azaheterocycles from
pharmacologists, synthetic chemists, and theorists has persis-
tently been increased due to not only variety of bioactivities, but
also high reactivity and some unique properties of these
compounds [1,6].
We have recently reported the first simultaneous synthesis of
3-methoxy-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-azepine
(1a) and 6-methoxy-2-methyl-3H-azepine (2a) starting from
readily accessible methoxyallene, isopropyl isothiocyanate and
MeI (Scheme 1) [8a]. The process comprises a one-pot synthesis
of 1-aza-1,3,4-triene 3a, its thermally induced rearrangement
into 2-aza-1,3,5-triene 4a [10] and an unprecedented reorgani-
zation of the latter into seven-membered azaheterocycles 1a and
2a under the action of t-BuOK (Scheme 1).
1-Isopropyl-3-methoxy-2-(methylsulfanyl)pyrrole (5a) and,
in some cases, 5-methoxy-2,2-dimethyl-6-(methylsulfanyl)-2,3-
1
dihydropyridine (6a) were identified ( H NMR) as a side prod-
ucts of the 2-aza-1,3,5-triene 4a synthesis [10a].
Such an unexpected structural transformation of 4-methoxy-
2-aza-1,3,5-triene 4a in the presence of t-BuOK (1.2 equiv) under
an unusually mild reaction conditions [THF/DMSO (5/1, v/v), ꢀ30
Now it has been well documented that the introduction of
heteroatom-containing substituents, above all, alkoxy and alkyl-
sulfanyl groups, to different positions of the carbo- or heterocyclic
ring can change drastically the physical, chemical, and biological
properties of the corresponding derivatives [7]. However, apart
ꢁ
to ꢀ25 C, 30 min] [8a] would be of higher synthetic value if it
could be applied to other 4-alkoxy-2-aza-1,3,5-trienes available
from alkoxyallenes, isothiocyanates, and alkyl halides [10].
Therefore, to extend further this novel and simple approach to
alkoxy- and alkylsulfanyl-substituted 4,5-dihydro-3H-azepines
and 3H-azepines, we proceeded to study the reaction of conju-
gated azatrienic systems with t-BuOK on new representatives
of alkoxyallene/isothiocyanate-based 2-aza-1,3,5-trienes
details.
4 in
*
Corresponding author. Fax: þ7 3952 419346.
E-mail address: nina@irioch.irk.ru (N.A. Nedolya).
0
022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.07.016

3
360
N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
OMe
SMe
After aqueous workup, followed by concentration of ethereal
solution under reduced pressure at room temperature, along with
1-aza-1,3,4-trienes 3aeg, 2-aza-1,3,5-trienes 4aeg (10e46%) and
some amounts (mainly 1e3%) of pyrroles 5beg (as by-products)
N
Me
Me
1
were identified ( H NMR) in crude products. This indicates that
5
a
(~10%) as by-product
ꢁ
already at w20 C, during evaporation of solvents, both concurrent
i. n-BuLi, THF/hexane
reactions of very reactive 1-aza-1,3,4-trienes 3, namely [1,5]-
sigmatropic rearrangement into 2-aza-1,3,5-trienes 4 and intra-
molecular [1,5]-cyclization into pyrroles 5, take place. Moreover, as
seen from Table 1, the rate of this isomerization to conjugated
azatrienes 4 increased when more bulky and in the same time more
electron donating, than OMe or SMe, substituents were attached to
initial 1-aza-1,3,4-triene 3. In all these cases, the content of 2-aza-
1,3,5-trienes 4 in a mixture with 1-aza-1,3,4-trienes 3 was w2ꢀ5
ii. Me CHN=C=S
2
C
OMe
OMe iii. MeI
Me
[1,5]-H shift
C
o
~
65 C, 15 min
Me
N
3a
SMe
t-BuOK
OMe
OMe
Me
Me
OMe
+
THF/DMSO
N
N
SMe Me
1a (~33%)
N
SMe
Me
1
2
times higher than when R ¼ R ¼ Me.
4
a
2a (~38%)
The isomerization of 1-aza-1,3,4-trienes 3 into the target 2-aza-
1
,3,5-trienes 4 was completed by heating of the products mixture at
OMe
SMe
ꢁ
55ꢀ67 C for 10ꢀ20 min at reduced pressure (on rotary evapo-
Me
Me
rator), the content of pyrrole 5 in a mixture with azatriene 4 being
increased up to 5e20% (Table 1). It should be noted that due to high
reactivity of 2-aza-1,3,5-trienes 4 it was impossible to get rid of the
impurities of pyrroles 5 by standard practices, because during the
vacuum distillation they cyclized into 2,3-dihydropyridines [10a],
N
6a
(~10%) as by-product
Scheme 1. Synthesis and transformation of azatrienes 3 and 4.
and upon chromatographic separation on a column with Al
2 3
O or
SiO they decomposed. This is why, in further reactions with
t-BuOK 2-aza-1,3,5-trienes 4, contaminated with pyrroles 5, were
2
2
. Results and discussions
used.
2.1. Preparation of 1-aza-1,3,4-trienes 3 and 2-aza-1,3,5-trienes 4
A wide range of azatrienic systems may be easily prepared from
2.2. Reaction of 2-aza-1,3,5-trienes 4 with t-BuOK. Synthesis of
4,5-dihydro-3H-azepines 1 and 3H-azepines 2
readily available dienes or alkynes, isothiocyanates and alkylating
agents according to procedures developed by us [10a]. For example,
alkoxy- and allyloxy-substituted 1-aza-1,3,4-trienes 3aeg (as
a mixture of syn- and anti-izomers), precursors of 2-aza-1,3,5-
trienes 4aeg, were synthesized in good to excellent yields
80e100%) from the corresponding alkoxyallenes (methoxy-,
ethoxy-, isopropoxy-, tert-butoxy-, and allyloxyallenes), isopropyl
isothiocyanate and alkyl iodides in one preparative step (Table 1).
In typical experiment, 2-aza-1,3,5-trienes 4aeg, without prelim-
inary purification, were treated with potassium tert-butoxide to give
the earlier unknown and inaccessible alkoxy- and alkylsulfanyl-
substituted 4,5-dihydro-3H-azepines 1aeg and 3H-azepines 2aec,
e (Table 2). The reactionwascarried out indry THF/DMSO (4e5:1, v/v)
(
ꢁ
at wꢀ30 C for 30 min with excess (1.15e1.48 equiv) of t-BuOK. After
Table 1
Synthesis and isomerization of 1-aza-1,3,4-trienes 3 into 2-aza-1,3,5-trienes 4, attended by parallel cyclization into pyrroles 5.
R1
R2
Content of the reaction
products by H NMR (%)
Total
yield (%)
Temp.
( C)
Reaction
time (min)
Conversion of 1-aza-1,
3,4-triene 3 (%)
Content of the reaction products
1
a
ꢁ
by H NMR (%)b
1
1
4
-Aza-1,3,
-triene 3
2-Aza-1,3,
5-triene 4
Pyrrole 5
2-Aza-1,3,5-triene 4
Pyrrole 5
Me
Et
i-Pr
t-Bu
Me
Me
Me
Me
Me
Et
a
b
c
d
e
f
90
60
52
72
77
80
64
10
30
46
26
22
18
28
0
10
2
2
1
98
99
97
97
80
58e60
58e60
56e60
55e60
60e67
58e60
58e60
10
10
10
10
20
15
10
100
100
100
100
100
100
100
90
80
95
95
90
85
90
10
20
5
5
CH
2
CH]CH
2
10
15
10
Me
Me
2
3
93
100
n-Bu
g
a
After synthesis of 1-aza-1,3,4-trienes 3aeg, workup and removal of solvents on rotary evaporator at room temperature.
After thermally induced isomerization of 1-aza-1,3,4-trienes 3aeg into 2-aza-1,3,5-trienes 4aeg.
b

N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
3361
aqueous workup, mixtures (except for 4,5-dihydro-3H-azepine 1d) of
compounds 1 and 2 were obtained in modest to good total yields
enimidothioate (7) and N-(but-1-enyl)-N’-butyl-N-[2-methoxy-1-
(methylsulfanyl)buta-1,3-dienyl]thiourea (8) in the reaction of
2-aza-1,3,5-triene 4h, derived from 1-lithio-1-methoxyallene,
n-butyl isothiocyanate and MeI, with t-BuOK under the above
conditions (Scheme 2) [11]. In this case, perhaps, due to sterical
hindrance of terminal ethyl group, formation of the corresponding
4,5-dihydro-3H-azepine 1h and 3H-azepine 2h was not observed.
Some additional evidence supporting the mechanism (Scheme
of Table 2) is provided by the reaction of 2-aza-1,3,5-triene 4a with
(Table 2). Also, the corresponding pyrroles 5, which were present in
the starting 2-aza-1,3,5-trienes 4 (Table 1), were isolated. Interest-
ingly, pyrroles 5 remained absolutely inert in this reaction and were
recovered without apparent loss.
We believe that the mechanism of the formation of 4,5-dihydro-
3
H-azepines 1 and 3H-azepines 2 in our case corresponds to that
depicted in Scheme of Table 2. Indeed, the reorganization of 2-aza-
,3,5-trienes into seven-membered azaheterocycles likely
involves the deprotonation of the methyl group from the azome-
thine moiety, N]C(CH , with t-BuOK to form azatrienic anions A.
ꢁ
1
4
0.5 equiv of t-BuOK in THF (0 C, 10 min). In this case, conversion of
the starting compound 4a was only w50%. But when 1.0e1.5 equiv
of t-BuOK were used, the conversion of 4a under similar conditions
was quantitative. This means that potassium tert-butoxide in the
reorganization of 2-aza-1,3,5-trienes 4 plays a role of stoichiometric
deprotonating base (potassiating agent) but not a catalyst. In
addition, with a weaker base, sodium tert-butoxide (1.0e1.5 equiv,
3 2
)
The latter undergo isomerization to anions B, followed by simul-
taneous [1,7]-electrocyclization to azacycloheptadienyl anionic
species C (Table 2). An unprecedented elimination of the thiolate-
2
ꢀ
anion (R S ) from cyclic anions C under the reaction conditions
affords 3H-azepines 2. Whilst, the protonation of these anionic
species upon aqueous workup gives (directly or after hydrogen
shifts) 4,5-dihydro-3H-azepines 1.
ꢁ
THF, 0 C, 10 min), transformation of compound 4a into 4,5-
dihydro-3H-azepine 1a and 3H-azepine 2a was not realized.
At the present time, the reactions of [1,7]-electrocyclization of
azatrienyl anions [12] and unsaturated azomethine ylides [13]
become one of the most simple and attractive approaches to the
construction of the dihydroazepine rings, mostly 1H-derivatives,
The proposed formation of isomerized anions of type B, as
intermediary species, unexpectedly received experimental support
by isolation of methyl (Z)-N-[(Z)but-1-enyl]-2-methoxybut-2-
Table 2
Ratio and yieldb of 4,5-dihydro-3H-azepines 1aeg and 3H-azepines 2aec, e.
a
4,5-Dihydro-3H-azepine 1
3H-Azepine 2
Ratio of 1/2
Yield (%) of
pyrrole 5
Structure
Yield (%)
Structure
Yield (%)
38
OMe
23
OMe
a
c
c
55:45
10
N
SMe
33
Me
N
38
Me
OEt
OEt
b
c
d
e
f
23
57
31
26d
38
34
18
0
55:45
85:15
100:0
65:35
70:30
28
6
Me
Me
Me
Me
Me
N
N
N
N
N
SMe
Me
Me
Me
Me
Me
N
N
N
N
N
OPr-i
OPr-i
OBu-t
O
SMe
OBu-t
15
16d
19
SMe
O
31d
20e
SMe
OMe
SEt
OMe
OMe
OMe
g
36
14e
80:20
12
Me
N
SBu-n
Me
N
a
b
c
In crude products (by 1H NMR).
After rough separation of products by column chromatography on Al
After treatment of the reaction mixture with w1.5% solution of hydrochloric acid [8a].
After rough separation of products with w3% solution of hydrochloric acid.
2 3
O .
d
e
3
H-Azepine 2a.

3362
N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
OMe
anionic species B (Table 1). The reasons of apparent suppression of
the process of thiolate-anions elimination, resulted in the forma-
tion of 3H-azepine, also remain obscure.
C
N
i.
n
-BuLi, THF/hexane
ii.
n
-BuN=C=S
iii. MeI
We have also studied the effects of different substituents at
sulfur atom in 2-aza-1,3,5-trienes 4 or in anionic species B (Table 1)
on a ratio of 4,5-dihydro-3H-azepine 1/3H-azepine 2. As can be
seen from the Table 2, a ratio of seven-membered azaheterocycles
1a, f, g and 2a, f, g significantly depends on the substituent at the
sulfur atom, as exemplified by deprotonation of methylsulfanyl-
ethylsulfanyl- and butylsulfanyl-substituted 2-aza-1,3,5-trienes 4a,
f, g, obtained from methoxyallene, isopropyl isothiocyanate and
methyl, ethyl, and butyl iodides, respectively.
By analogy with the trends demonstrated by alkoxy substituents
at their variation, the increase of the substituent size at the sulfur
atom leads to an increase of 4,5-dihydro-3H-azepine content in
a mixture of products. Thus, on going from methylsulfanyl to
bulkier ethylsulfanyl and butylsulfanyl substituents, the ratio of
dihydroazepine/azepine changed noticeably in favor of the corre-
sponding 4,5-dihydro-3H-azepines, from 55:45 to 70:30 and to the
80:20, respectively. But, as in the case of alkoxy substituents, it is
not clear whether this ratio depends on steric or electronic effects
of the SR groups or on both.
SMe
t
-BuOK
Et
N
Et
THF/DMSO
Et
OMe
SMe
OMe
SMe
+
30 oC, 30 min
−
MeO
Me
N
7
(~11%)
Bu
4h
N
H
S
8 (~5%)
t
-BuOK
OMe
SMe
H O
2
i.
n
-BuN=C=S
−
H
Et
ii. H O
Et
Et
OMe
SMe
2
−
N
A'
N
B'
X
OMe
SMe
Et
OMe
+
/or
N
1h
N
2h
Scheme 2. Synthesis and transformations of azatriene 4h.
and some other heterocycles. The synthesis of azepines via copper-
mediated [1,7]-cyclization of 2-aza-hepta-2,4-dien-6-ynyl anions
was also reported [14]. Nevertheless, the structures of starting and
final compounds (including character and positions of the
substituents), the reaction conditions, deprotonating base (LDA)
Previous [8a] and present studies have shown that the ratio of
compounds 1 and 2 (as well as the content of by-products, pyrroles
5 and 2,3-dihydropyridines 6) are also influenced by the reaction
conditions. For example, as was described above, the deprotonation
ꢁ
and structural fragment under the deprotonation (CH
2
N]C) in
of 2-aza-1,3,5-triene 4a in THF/DMSO (t-BuOK, ꢀ30 C, 30 min) led
published works are cardinally different from described here.
Moreover, apart from our own previous works [8] as well as the
results reported already in this paper, there are no any method-
ology providing the construction of both azepine and dihy-
droazepine rings from common precursor, namely 2-aza-1,3,5-
triene, via its reorganization under the same reaction conditions.
It is also necessary to note that the most usual base for metallation
to a mixture of 4,5-dihydro-3H-azepine 1a and 3H-azepine 2a in
a ratio of w55:45. But the same compounds were obtained in
a ratio of w75:25 when this reaction was carried out in THF (in the
ꢁ
absence of DMSO) at 0 C for 10 min [8a]. Along with 4,5-dihydro-
3H-azepine 1a (47%) and 3H-azepine 2a (13%), pyrrole 5a (33%) and
2,3-dihydropyridine 6a (7%) were obtained under these conditions.
ꢁ
When this reaction was performed in THF at ꢀ5 to 0 C for 60 min
1
2
1
of aldimines, N]CHR, and ketimines, N]CR R (where R, R and
the same four compounds were prepared in almost the same
proportions. Thus, increase of the reaction time changed neither
composition nor the ratio of products. When 2-aza-1,3,5-triene 4a
was added dropwise (for 5 min) to a solution of t-BuOK (0.9 equiv)
2
R ¼ alkyl or cycloalkyl), is LDA [15], and to the best of our knowl-
edge, t-BuOK was never employed for this purpose.
During these researches, we have not found any obvious
differences in reactivity of alkoxy-substituted 2-aza-1,3,5-trienes
aeg toward t-BuOK under the investigated conditions. In all the
cases, their conversion was quantitative. At the same time, the yield
and the ratio of seven-membered azaheterocycles, as it was found,
depend strongly on the substituent at the oxygen atom. Thus,
replacement of the methoxy group in 2-aza-1,3,5-triene 4a by more
bulky alkoxy substituents, namely, isopropoxy group (compound
ꢁ
in THF at ꢀ85 to ꢀ65 C and the temperature was allowed to rise
ꢁ
4
to ꢀ5 C for 2e3 min, compounds 1a, 2a and 5a were formed in the
1
ratio of w60:10:30 ( H NMR). Signals of starting 2-aza-1,3,5-triene
4a were also present in H NMR spectrum of the reaction mixture.
1
But 2,3-dihydropyridine 6a was not identified in this case. The
ꢁ
reaction was completed by additional stirring at ꢀ5 to 0 C for
10 min. This experiment clearly demonstrates that even in the
absence of DMSO, the transformation of 2-aza-1,3,5-trienes 4 into
4,5-dihydro-3H-azepines and 3H-azepines, provoked by t-BuOK, is
exceptionally easy and very fast process. In this case, the large
excess of the base was specially created by adding of 2-aza-1,3,5-
triene 4a to a solution of t-BuOK in THF dropwise.
4
c) led to noticeable change of a ratio of the corresponding 4,5-
dihydro-3H-azepine 1c and 3H-azepine 2c in favor of the former,
the content of which in mixture with azepine 1 being increased
1
1
from 55 (R ¼ Me) to 85 % (R ¼ i-Pr). When tert-butoxy-substituted
-aza-1,3,5-triene 4d was used, the reaction with t-BuOK gave 4,5-
dihydro-3H-azepine 1d as a single reaction product.
-Aza-1,3,5-triene 4e, bearing allyloxy substituent, also
smoothly reacts with potassium tert-butoxide yielding a mixture of
,5-dihydro-3H-azepine 1e and 3H-azepine 2e in a ratio of w65:35.
2
Rough separation of the reaction products by column chroma-
2
tography on Al
chloric acid and final purification on Al
2
O
3
, followed by treatment with diluted hydro-
afforded individual
2 3
O
4
compounds. It was also shown on the products derived from 2-aza-
1,3,5-triene 4a that when the reaction mixture was at first treated
with w1.5% solution of hydrochloric acid (instead of water), 3H-
azepine 2a was isolated directly in 38% yield (from acidic aqueous
layer). 4,5-Dihydro-3H-azepine 1a was then isolated from the
mixture with pyrrole 5a by additional treatment with w8% solution
of hydrochloric acid, followed by neutralization and extraction of
acidic aqueous solution. The yield of compound 1a was 10% higher
than that obtained by previous procedure for separation of the
reaction products (see Table 2). As was also found on the example of
the derivatives of 2-aza-1,3,5-triene 4a, mixtures of three (1a, 2a,
and 5a) or of four (1a, 2a, 5a, and 6a) azaheterocycles, were
Allylepropenyl isomerization of the starting or final compounds
under the reaction conditions was not observed.
Similar to methoxy-substituted 2-aza-1,3,5-triene 4a, ethoxy
derivative 4b under the action of superbasic system t-BuOK/THF/
DMSO was transformed into the corresponding 4,5-dihydro-3H-
azepine 1b and 3H-azepine 2b in a ratio of w55:45. In both these
cases, preferential formation of 4,5-dihydro-3H-azepine 1 was less
obvious in comparison with azatrienes 4cee.
But it is not clear, is this due to the very high sensitivity of
products ratio to the substituents structure, i.e. their steric or
electronic effects or both, as well as e in 2-aza-1,3,5-trienes 4 or in

N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
3363
inseparable by vacuum distillation. Moreover, significant amount of
tar (up to w60%) was formed during the distillation. As a rule, each
subsequent purification of 4,5-dihydro-3H-azepines 1 by column
chromatography leads to serious decreasing of their isolated yields.
Obviously, 4,5-dihydro-3H-azepines 1 are less chemically stable
than the corresponding azepines 2.
Full spectral data for all novel compounds are given below, all
previously characterized compounds gave spectra consistent with
the literature.
4.2. General procedure 1: preparation of 1-aza-1,3,4-trienes 3aeg
The structures of the products have been assigned using H, 13C,
1
To a stirred solution of n-BuLi (51.2e64 mmol, 32e40 mL for
3aed and 52.5e60 mmol, 21e24 mL for 3eeg) in THF (45e70 mL),
1
1
1
13
homo- and heteronuclear 2D ( He H COSY-45, He C HSQC,
1
13
1
15
ꢁ
He C and He N HMBC) NMR and IR spectroscopy and mass-
spectrometry.
at ꢀ100 C, corresponding allene (50.1e87.8 mmol) was added
ꢁ
(Table 1). After stirring for an additional 10 min at wꢀ70 to ꢀ60 C,
ꢁ
the solution was cooled to ꢀ90 C and a mixture of isopropyl iso-
thiocyanate (50 mmol, 5.05 g) and THF (5 mL) was added in one
portion. The temperature of the reaction mixture was allowed to
3
. Conclusion
ꢁ
rise to wꢀ30 C, which level was maintained for an additional
In conclusion, we report herein that the azepines and dihy-
droazepines bearing rare substituents such as earlier unknown and
inaccessible by other methods 6-alkoxy-3H-azepines and 3-alkoxy-
ꢁ
1
(
5e20 min. The solution was cooled to ꢀ80 C and alkyl iodide
70.5e112.7 mmol, 12e16 g, excess) was then added in one portion,
after which the temperature was allowed to rise to 20 C for
ꢁ
2
-(alkylsulfanyl)-4,5-dihydro-3H-azepines, can be simultaneously
ꢁ
3
0e40 min. The mixture was cooled to ꢀ80 C, and then quenched
obtained from alkoxyallenes, isopropyl isothiocyanate and alky-
lating agents via one-pot synthesis and deprotonation of 2-aza-
with sat. aq solution of NH
4
Cl (100 mL) and extracted with Et
2
O
O
(
(
3 ꢂ 30 mL). The combined organic extracts were washed with H
2
1,3,5-trienes. This simple and efficient strategy of easy and fast
3 ꢂ15 mL), dried (MgSO
4
) and concentrated under a reduced
reorganization of conjugated azatrienes under the action of
ꢁ
pressure at a bath temperature of w20 C to give a residue con-
sisting of corresponding 1-aza-1,3,4-triene 3 as a mixture of syn-
and anti-isomers in admixture with 2-aza-1,3,5-triene 4 and
ꢁ
potassium tert-butoxide in THF/DMSO (ꢀ30 C, 30 min) allowed us
to significantly expand the range of alkoxy- and alkylsulfanyl-
substituted 4,5-dihydro-3H-azepines and 3H-azepines and to
make these synthetically and pharmacologically promising
compounds easily accessible.
pyrrole
5 traces. Yields and characteristic data of 1-aza-
1,3,4-trienes 3aeg are reported below.
Additionally, these results underscore a generality of the
strategy and the synthetic potential of azatrienic systems, easily
accessible building blocks for the design of various classes of
heterocycles (thietanes [16], thiophenes [17], thiopyrans [18],
pyrroles [17a,19], pyridines [20], dihydropyridines [20,21], quino-
lines [19c,21a,c,22], azepines [8], etc.) [10].
Work is now in progress to extend the synthetic value of this
approach to seven-membered azaheterocycles using 2-aza-1,3,5-
trienes, derived from allenic or acetylenic carbanions and other
sec-alkyl or cycloalkyl isothiocyanates.
4
3
4
.2.1. Methoxyallene (87.8 mmol, 6.15 g); n-BuLi (51.2 mmol in
2 mL of hexane); MeI (91.5 mmol, 13 g); THF (70 mL)
.2.1.1. Methyl N-isopropyl-2-methoxy-2,3-butadienimidothioate
(
3a). Yield: 9.06 g (98%); light-brown liquid. IR (neat): 1949
ꢀ
1
1
(
CH
C]C]C) cm [8a,10a]; H NMR: major isomer,
d
5.71 (s, 2H,
], 3.50 (s, 3H,
OMe), 2.41 (s, 3H, SMe), 1.18 [d, J ¼ 6.3 Hz, 6H, NCH(CH ];
]), 3.97 [septet, J ¼ 6.1 Hz, 1H,
], 3.42 (s, 3H, OMe), 2.27 (s, 3H, SMe), 1.11 [d,
3
2
]), 3.92 [septet, J ¼ 6.3 Hz, 1H, NCH(CH
3 2
)
3
3 2
)
3
minor isomer,
NCH(CH
d 5.65 (s, 2H, CH
2
3 2
)
3
13
J ¼ 6.1 Hz, 6H, NCH(CH
isomer, 200.11 (]C]), 174.20 (C]N), 156.31 (C-2), 92.91
(CH ]), 56.15 (OMe), 53.74 [NCH(CH ], 22.65 [NCH(CH ],
5.09 (SMe); minor isomer, 198.44 (]C]), 172.97 (C]N), 154.26
(C-2), 93.26 (CH ]), 55.87 (OMe), 53.91 [NCH(CH ], 24.00
NCH(CH ], 13.77 (SMe).
3 2
) ]; in a ratio of w60:40; C NMR: major
d
4
. Experimental
2
3
)
2
3 2
)
1
d
4.1. General
2
3 2
)
[
3 2
)
Isopropyl isothiocyanate and alkoxyallenes were prepared as
described in the literature [10a,23]. n-BuLi (1.6 and 2.5 M solution
in hexane), t-BuOK and solvents are commercially available. All
solvents were purified according to standard procedures. All reac-
tions (with the exception of isomerization of 1-aza-1,3,4-trienes
into 2-aza-1,3,5-trienes) were performed under anhydrous condi-
tions and in an argon atmosphere. For all reactions at low
temperatures a cooling bath with liquid nitrogen was used. All
reactions were monitored by TLC on precoated with Merck silica gel
4.2.2. Ethoxyallene (85.8 mmol, 7.21 g); n-BuLi (64 mmol in 40 mL
of hexane); MeI (112.7 mmol, 16 g); THF (70 mL)
4.2.2.1. Methyl
2-ethoxy-N-isopropyl-2,3-butadienimidothioate
(3b). Yield: 9.90 g (99%); red-brown mobile liquid. IR (neat):
ꢀ
1 1
1952 (C]C]C) cm ; H NMR: major isomer,
d
5.59 (s, 2H, CH
2
]),
], 3.62 (q, J ¼ 7.0 Hz, 2H,
), 2.26 (s, 3H, SMe), 1.28 (t, J ¼ 7.0 Hz, 3H, OCH CH ), 1.12
[d, J ¼ 6.2 Hz, 6H, NCH(CH ]; minor isomer, 5.63 (s, 2H, CH ]),
3.84 [septet, J ¼ 6.2 Hz, 1H, NCH(CH ], 3.69 (q, J ¼ 7.0 Hz, 2H,
), 2.43 (s, 3H, SMe), 1.30 (t, J ¼ 7.0 Hz, 3H, OCH CH ), 1.17
]; in a ratio of w50:50; C NMR:
199.91 (]C]), 173.84 (C]N), 156.73 (C-2), 92.40
]), 66.56 (OCH CH ), 53.63 [NCH(CH ], 22.66, 22.62
[NCH(CH ], 15.50 (SMe), 14.65 (OCH CH ); minor isomer 199.07
(]C]), 173.84 (C]N), 154.40 (C-2), 91.89 (CH ]), 64.69
(OCH CH ), 53.90 [NCH(CH ], 24.12, 24.08 [NCH(CH ], 15.45
(SMe), 14.60 (OCH CH ).
3
3
3.84 [septet, J ¼ 6.2 Hz, 1H, NCH(CH
3 2
)
3
OCH
2
CH
3
2
3
3
3
)
2
d
2
3
3
6
0 F254 plates, were visualised by exposure to iodine vapour.
IR spectra were measured neat or as KBr pellets on a Bruker
3 2
)
3
OCH
2
CH
3
2
3
1
13
3
13
Vertex-70 infrared spectrophotometer. The H (400.13 MHz),
100.62 MHz) and 15N (40.55 MHz) NMR spectra were recorded on
a Bruker DPX-400 and Bruker AV-400 spectrometers in CDCl
solution at an ambient temperature. Chemical shifts ( ) are quoted
in ppm, to the nearest 0.01 ppm, and are referenced to HMDS (for
C
[d, J ¼ 6.2 Hz, 6H, NCH(CH
major isomer,
(CH
3 2
)
(
d
3
2
2
3
3 2
)
d
3
)
2
2
3
d
2
1
13
15
H and C) and MeNO
2
(for N) as internal standards. Coupling
2
3
3
)
2
3 2
)
constants (J) are reported in Hertz (Hz) to the nearest 0.1 Hz.
Assignments of spectra were carried out using 2D experiments. The
mass spectra (electron impact, 70 eV) were recorded on a Shimadzu
GCMS-QP5050A instrument. The microanalyses were performed
on a Flash EA 1112 Series elemental analyzer. Melting point was
determined using a Kofler micro hot stage.
2
3
4.2.3. Isopropoxyallene (50.1 mmol, 4.91 g); n-BuLi (60.8 mmol in
38 mL of hexane); MeI (91.5 mmol, 13 g); THF (70 mL)
4.2.3.1. Methyl 2-isopropoxy-N-isopropyl-2,3-butadienimidothioate
(3c). Yield: 10.34 g (97%); light-brown mobile liquid. IR (neat):

3364
N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
ꢀ
1
4
1
947 (C]C]C) cm 1; 1H NMR: major isomer,
d
5.56 (s, 2H, CH
2
]),
24.14 (SCH
minor isomer,
(CH ]), 56.33 (OMe), 54.02 [NCH(CH
3
23.60, 23.45 [NCH(CH ], 21.17 (SCH CH ).
2
CH
d
3
), 22.93, 22.78 [NCH(CH
199.01 (]C]), 173.51 (C]N), 154.96 (C-2), 93.26
], 24.05 (SCH CH ),
3 2 2 3
) ], 21.27 (SCH CH );
.04 [septet, 3J ¼ 6.1 Hz, 1H, OCH(CH
)
2
], 3.97 [septet, J ¼ 6.2 Hz,
3
3
3
H, NCH(CH
3
)
2
], 2.26 (s, 3H, SMe), 1.23 [d, J ¼ 6.1 Hz, 3H,
2
3
)
2
2
3
3
OCH(CH
d
3
)
2
], 1.11 [d, J ¼ 6.2 Hz, 6H, NCH(CH
3
)
2
]; minor isomer,
], 3.84
], 2.46 (s, 3H, SMe), 1.26 [d,
3
)
2
2
3
5.60 (s, 2H, CH
2
]), 4.03 [septet, J ¼ 6.2 Hz, 1H, OCH(CH
3 2
)
[
septet, 3J ¼ 6.3 Hz, 1H, NCH(CH
3
)
2
4.2.7. Methoxyallene (71.4 mmol, 5 g); n-BuLi (60 mmol in 24 mL of
hexane); n-BuI (71.7 mmol, 13.2 g); THF (45 mL)
4.2.7.1. Butyl N-isopropyl-2-methoxy-2,3-butadienimidothioate
3
3
J ¼ 6.2 Hz, 3H, OCH(CH
3
)
2
], 1.16 [d, J ¼ 6.3 Hz, 6H, NCH(CH
199.84 (]C]), 170.28
]), 70.99 [OCH(CH ], 53.60
], 21.62 [NCH(CH ], 12.96 (SMe);
]), 71.42 [OCH(CH ], 53.40
], 21.37 [NCH(CH ], 12.92 (SMe).
Signals of C-2, C]N, and ]C] groups are not cumulated.
3 2
) ]; in
a ratio of w60:40; 13C NMR: major isomer,
d
(
[
C]N), 154.53 (C-2), 91.77 (CH
NCH(CH ], 23.99 [OCH(CH
91.05 (CH
], 22.48 [OCH(CH
2
3
)
2
(3g). Yield: 11.35 g (100%); brown mobile liquid. IR (neat):
ꢀ
1
1
3
)
2
3
)
2
3
)
2
1947 (C]C]C) cm
CH
]), 4.01 [septet, J ¼ 6.2 Hz, 1H, NCH(CH
OMe), 2.88 (t, J ¼ 7.4 Hz, 2H, SCH
;
H NMR: major isomer,
d
5.72 (s, 2H,
3
minor isomer,
NCH(CH
d
2
3
)
2
2
3 2
) ], 3.50 (s, 3H,
3
3
[
3
)
2
3
)
2
3
)
2
2
Pr), 1.56 (quintet, J ¼ 7.4 Hz,
Et), 1.39 [sextet, J ¼ 7.4 Hz, 2H, S(CH CH CH ],
], 0.90 [t, J ¼ 7.4 Hz, 3H,
5.64 (s, 2H, CH ]), 3.95 [septet,
], 3.44 (s, 3H, OMe), 2.88 (t, J ¼ 7.4 Hz,
3
2H, SCH
2
CH
2
2
)
2
2
3
3
3
1
.18 [d, J ¼ 6.2 Hz, 6H, NCH(CH
S(CH CH ]; minor isomer,
J ¼ 6.2 Hz, 1H, NCH(CH
2H, SCH
Pr), 1.56 (quintet, J ¼ 7.4 Hz, 2H, SCH
3 2
)
4
3
4
(
1
.2.4. tert-Butoxyallene (55.1 mmol, 6.17 g); n-BuLi (56 mmol in
5 mL of hexane); MeI (84.5 mmol, 12 g); THF (70 mL)
.2.4.1. Methyl 2-(tert-butoxy)-N-isopropyl-2,3-butadienimidothioate
2
)
3
3
d
2
3
3
3 2
)
3
2
2
CH
2
Et), 1.39
], 1.09 [d, J ¼ 6.2 Hz, 6H,
], 0.91 [t, J ¼ 7.4 Hz, 3H, S(CH CH ]; in a ratio of
200.77 (]C]), 160.27 (C]N),
]), 56.18 (OMe), 53.90 [NCH(CH ],
Pr), 23.91 (SCH CH Et), 22.75 [NCH(CH ], 21.71
CH ], 13.44 [S(CH CH ]; minor isomer, 203.96 (]
C]), 160.27 (C]N), 155.18 (C-2), 93.11 (CH ]), 56.31 (OMe),
53.80 [NCH(CH ], 29.18 (SCH Pr), 23.90 [NCH(CH ], 21.98
(SCH CH Et), 21.79 [S(CH CH CH ], 13.54 [S(CH CH ].
3
3
3d). Yield: 11.00 g (97%); light-brown mobile liquid. IR (neat):
[sextet, J ¼ 7.4 Hz, 2H, S(CH
2 2 2 3
) CH CH
ꢀ
1
1
3
948 (C]C]C) cm ; H NMR: major isomer,
d
5.45 (s, 2H, CH
], 2.49 (s, 3H, SMe),1.37 [s, 9H,
]; minor isomer, 5.47
], 2.24 (s, 3H,
], 1.11 [d, J ¼ 6.2 Hz, 6H, NCH(CH ]; in
a ratio of w60:40; 13C NMR: major isomer,
202.80 (]C]), 173.34
]), 79.72 [OC(CH ], 53.44
], 24.00 [NCH(CH ], 13.07 (SMe);
202.80 (]C]), 173.34 (C]N), 156.66 (C-2), 87.63
]), 79.92 [OC(CH ], 53.48 [NCH(CH ], 29.61 [OC(CH ],
2.44 [NCH(CH ], 13.07 (SMe).
2
]),
NCH(CH
3
)
2
2
)
3
3
3
13
3
.85 [septet, J ¼ 6.4 Hz,1H, NCH(CH
)
3 2
w70:30; C NMR: major isomer,
153.48 (C-2), 92.69 (CH
32.40 (SCH
[S(CH CH
d
3
OC(CH
)
3 3
], 1.15 [d, J ¼ 6.4 Hz, 6H, NCH(CH
)
3 2
d
2
3 2
)
3
(
s, 2H, CH
2
]), 4.10 [septet, J ¼ 6.2 Hz, 1H, NCH(CH
)
3 2
2
2
2
3 2
)
3
SMe), 1.36 [s, 9H, OC(CH
)
3 3
)
3 2
2
)
2
2
3
2
)
3
3
d
d
2
(
[
C]N), 155.70 (C-2), 89.26 (CH
NCH(CH ], 27.87 [OC(CH
2
)
3 3
3
)
2
2
3 2
)
)
3 2
)
3 3
)
3 2
2
2
2
)
2
2
3
2
)
3
3
minor isomer,
CH
d
(
2
2
)
3 3
3
)
2
)
3 3
4.3. General procedure 2: preparation of 2-aza-1,3,5-trienes 4aeg
by isomerization of 1-aza-1,3,4-trienes 3aeg
3 2
)
4
.2.5. Allyloxyallene (50.3 mmol, 4.83 g); n-BuLi (52.5 mmol in
The isomerization of 1-aza-1,3,4-trienes 3 into 2-aza-1,3,5-
trienes 4 was effected by rotating a sample on a rotary evaporator
at a bath temperature of 55e67 C for 10e20 min. The bath
21 mL of hexane); MeI (112.7 mmol, 16 g); THF (70 mL)
ꢁ
4.2.5.1. Methyl 2-(allyloxy)-N-isopropyl-2,3-butadienimidothioate
(
3e). Yield: 8.40 g (80%); dark mobile liquid. IR (neat): 1947
temperatures, reaction times, and conversions of 1-aza-1,3,4-
trienes are reported in Table 1; spectral data are reported below.
2-Aza-1,3,5-trienes 4 were used without further purification.
ꢀ
1 1
(
C]C]C) cm ; H NMR: major isomer,
), 5.62 (s, 2H, CH ]), 5.32, 5.20 (2d,
cis ¼ 10.5 Hz, 2H, OCH
OCH CH]CH
), 4.02 [septet, J ¼ 6.2 Hz, 1H, NCH(CH
H, SMe), 1.12 [d, J ¼ 6.2 Hz, 6H, NCH(CH
5.95 (m, 1H, OCH CH]CH ), 5.62 (s, 2H, CH
cis ¼ 10.5 Hz, 2H, OCH CH]CH
CH]CH
), 3.87 [septet, J ¼ 6.2 Hz, 1H,
], 2.42 (s, 3H, SMe), 1.17 [d, J ¼ 6.2 Hz, 6H,
d
5.95 (m, 1H, OCH
2
CH]
trans ¼ 17.1 Hz,
), 4.11 (d, J ¼ 5.4 Hz, 2H,
], 2.26 (s,
]; minor isomer,
]), 5.32, 5.20 (2d,
), 4.16 (d,
3
CH
2
2
J
3
3
J
2 2
CH]CH
3
2
2
3
)
2
4.3.1. 2-Methoxy-N-(1-methylethylidene)-1-(methylsulfanyl)-1,3-
3
3
d
3
3
)
2
butadien-1-amine (4a)
1
3
2
J
2
2
Dark mobile liquid [8a,10a]. H NMR:
d
5.91 (dd, Jtrans ¼ 17.1 Hz,
3
3
3
3
J
trans ¼ 17.1 Hz,
2
2
J
J
cis ¼ 10.8 Hz, 1H, CH]), 5.18, 4.90 (2dd,
J
trans ¼ 17.1 Hz,
3
3
J ¼ 5.8 Hz, 2H, OCH
2
2
cis ¼ 10.8 Hz, 2H, CH
2
]), 3.63 (s, 3H, OMe), 2.17 (s, 3H, SMe), 2.07,
3
13
NCH(CH
NCH(CH
3
)
)
2
1.89 [2s, 6H, N]C(CH
134.00 (C-1), 126.24 (CH]), 109.42 (CH
20.92 [N]C(CH ], 12.50 (SMe).
3
)
2
]; C NMR:
d
173.68 (C]N), 137.82 (C-2),
13
3
2
]; in a ratio of w50:50; C NMR: major isomer,
2
]), 58.15 (OMe), 27.53,
d
198.91 (]C]), 173.86 (C]N), 154.00 (C-2), 132.83 (OCH
2
CH]
CH]
3 2
)
CH
CH
isomer,
(
(
(
2
), 117.59 (OCH
), 53.58 [NCH(CH
199.87 (]C]), 173.86 (C]N), 156.34 (C-2), 132.96
2
CH]CH
2
), 92.37 (CH
2
]), 69.32 (OCH
2
2
3
)
2
], 24.02 [NCH(CH
3
)
2
], 12.95 (SMe); minor
4.3.2. 2-Ethoxy-N-(1-methylethylidene)-1-(methylsulfanyl)-1,3-
d
butadien-1-amine (4b)
1
3
OCH
2
CH]CH
CH]CH
2
2
), 118.02 (OCH
), 53.81 [NCH(CH
2
CH]CH
2
), 92.86 (CH
2
]), 69.70
], 14.75
Red-brown mobile liquid. H NMR:
d
5.93 (dd, Jtrans ¼ 17.2 Hz,
3
3
3
OCH
2
3
)
2
], 22.55 [NCH(CH
3
)
2
J
J
cis ¼ 10.9 Hz, 1H, CH]), 5.18, 4.88 (2dd,
J
trans ¼ 17.2 Hz,
cis ¼ 10.9 Hz, 2Jgem ¼ 1.8 Hz, 2H, CH
]), 3.83 (q, J ¼ 7.0 Hz, 2H,
], 1.33 (t,
173.76 (C]N), 137.12 (C-2),
134.30 (C-1), 126.94 (CH]), 109.30 (CH ]), 66.71 (OCH (CH ),
27.68, 21.12 [N]C(CH ], 15.32 [OCH (CH ], 12.72 (SMe).
3
SMe).
2
2 3 3 2
OCH (CH ), 2.17 (s, 3H, SMe), 2.06, 1.88 [2s, 6H, N]C(CH )
3
13
4
.2.6. Methoxyallene (71.4 mmol, 5 g); n-BuLi (57.5 mmol in 23 mL
of hexane); EtI (70.5 mmol, 11 g); THF (45 mL)
.2.6.1. Ethyl N-isopropyl-2-methoxy-2,3-butadienimidothioate
3f). Yield: 9.30 g (93%); brown mobile liquid. IR (neat): 1948
2 3
J ¼ 7.0 Hz, 3H, OCH (CH ); C NMR: d
2
2
3
4
3
)
2
2
3 2
)
(
(
[
ꢀ
1 1
C]C]C) cm ; H NMR: major isomer,
d
5.71 (s, 2H, CH
2
]), 3.99
4.3.3. 2-Isopropoxy-N-(1-methylethylidene)-1-(methylsulfanyl)-
septet, 3J ¼ 6.2 Hz, 1H, NCH(CH
1,3-butadien-1-amine (4c)
3 2
) ], 3.50 (s, 3H, OMe), 2.92 (q,
3
3
1
3
J ¼ 7.5 Hz, 2H, SCH
2
CH
3
), 1.27 (t, J ¼ 7.5 Hz, 3H, SCH
]; minor isomer, 5.64 (s, 2H,
]), 3.96 [septet, J ¼ 6.2 Hz, 1H, NCH(CH ], 3.44 (s, 3H,
2
CH
3
), 1.18
Light-brown mobile liquid. H NMR:
d
5.98 (dd, Jtrans ¼ 17.2 Hz,
3
3
3
3
[
d, J ¼ 6.2 Hz, 6H, NCH(CH
3
)
2
d
J
J
cis ¼ 11.0 Hz, 1H, CH]), 5.17, 4.88 (2dd,
J
trans ¼ 17.2 Hz,
3
2
3
CH
OMe), 2.87 (q, J ¼ 7.4 Hz, 2H, SCH
2
3
)
2
cis ¼ 11.0 Hz, Jgem ¼ 2.0 Hz, 2H, CH
2
]), 4.30 [septet, J ¼ 6.1 Hz,1H,
],1.26 [d,
173.51 (C]N), 135.92 (C-2),
134.46 (C-1), 128.13 (CH]), 110.23 (CH ]), 72.82 [OCH(CH ],
27.73, 21.38 [N]C(CH ], 22.37 [OCH(CH ], 12.98 (SMe).
3
3
2
CH
3
), 1.23 (t, J ¼ 7.4 Hz, 3H,
); in a ratio of
200.83 (]C]), 173.51 (C]N),
]), 56.41 (OMe), 53.99 [NCH(CH ],
OCH(CH
3
)
2
], 2.17 (s, 3H, SMe), 2.04,1.87 [2s, 6H, N]C(CH )
3 2
3
3
13
SCH
w70:30; C NMR: major isomer,
55.07 (C-2), 92.86 (CH
2
CH
3
), 1.10 (d, J ¼ 6.2 Hz, 6H, NCH(CH
3
)
2
J ¼ 6.1 Hz, 6H, OCH(CH
3 2
) ]; C NMR: d
13
d
2
3 2
)
1
2
3
)
2
3
)
2
3 2
)

N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
3365
4
.3.4. 2-(tert-Butoxy)-N-(1-methylethylidene)-1-(methylsulfanyl)-
hydrochloric acid. At that rate the pyrrole 5 remained in ethereal
solution and dihydroazepine 1 in the form of iminium salt passed
into aqueous phase from which, after neutralization with a w20%
1,3-butadien-1-amine (4d)
Dark viscous liquid. 1H NMR:
d
6.09 (dd,
3
3
J
J
trans ¼ 17.4 Hz,
trans ¼ 17.4 Hz,
3
J
cis ¼ 11.2 Hz, 1H, CH]), 5.24, 4.89 (2dd,
2
aq solution of KOH, was isolated by Et O. Both organic solution
3Jcis ¼ 11.2 Hz, Jgem ¼ 2.0 Hz, 2H, CH
2
]), 2.17 (s, 3H, SMe), 2.02, 1.86
were dried over MgSO . Concentration under reduced pressure,
2
4
1
3
[
2s, 6H, N]C(CH
3
)
2
], 1.40 [s, 9H, OC(CH
3
)
3
]; C NMR:
d
174.22 (N]
]), 81.69
3 3 3 3 3 2
OC(CH ) ], 30.56 [OC(CH ) ], 28.60, 22.65 [N]C(CH ) ], 14.02
followed by column chromatography, afforded pure dihy-
droazepine 1 and pyrrole 5. The ratios and yields are reported in
Table 2; physical and spectral data are reported below.
C), 136.67 (C-2), 135.35 (C-1), 132.23 (CH]), 112.38 (CH
[
(
2
SMe).
4.4.1. 2-Aza-1,3,5-triene 4a (40 mmol); t-BuOK (1.28 equiv); THF/
4.3.5. 2-(Allyloxy)-N-(1-methylethylidene)-1-(methylsulfanyl)-1,3-
DMSO, 4:1
butadien-1-amine (4e)
4.4.1.1. 3-Methoxy-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-aze-
1
3
3
Dark mobile liquid. H NMR:
d
6.07 (ddt, J ¼ 17.2 Hz, J ¼ 10.4 Hz,
pine (1a). Yield: 1.71 g (23%) after rough separation [8a] on Al
1.63 g (22%) after separation with HCl; light-yellow liquid; n
2 3
O ;
3
3
23
1
H, OCH
2
CH]CH
2
), 5.94 (dd,
J
trans ¼ 17.2 Hz,
J
cis ¼ 11.0 Hz, 1H,
CH]CH ),
gem ¼ 1.9 Hz, 2H,
CH]CH ), 2.17 (s,
]; C NMR: 174.10 (C]N),
36.97 (C-2), 134.88 (C-1), 134.39 (CH]), 126.96 (OCH CH]CH ),
17.19 (OCH CH]CH ),109.94 (CH ]), 71.76 (OCH CH]CH ), 27.94,
], 12.99 (SMe).
D
3
3
CH]), 5.36, 5.20 (2ddt, J ¼ 17.2 Hz, J ¼ 10.4 Hz, 2H, OCH
2
2
1.5188. IR (neat): 2976, 2942, 2924, 2857, 2825, 1631, 1572, 1551,
1511, 1451, 1439, 1411, 1376, 1349, 1336, 1311, 1247, 1208, 1176, 1139,
1112, 1084, 1058, 1036, 1008, 961, 913, 885, 798, 785, 727, 697, 679,
3
3
2
5
CH
.19, 4.88 (2dd,
J
trans ¼ 17.2 Hz,
J
cis ¼ 11.0 Hz,
J
3
4
2
]), 4.29 (dt, J ¼ 5.6 Hz, J ¼ 1.3 Hz, 2H, OCH
2
2
1
3
ꢀ1
1
3
3
H, SMe), 2.06, 1.88 [2s, 6H, N]C(CH
3
)
2
d
586, 527, 477, 450 cm
;
H NMR:
d
5.18 (ddq,
J
6,5’ ¼ 7.7 Hz,
3
3
4
6,Me ¼ 1.3 Hz, 1H, H-6), 4.00 (dd, 3J3,4’ ¼ 10.4 Hz,
1
1
2
2
J
J
6,5 ¼ 5.3 Hz,
J
2
2
2
2
2
3,4 ¼ 7.8 Hz, 1H, H-3), 3.36 (s, 3H, OMe), 2.47, 2.07 (2m, 2H, CH
2
-4),
4
21.42 [N]C(CH
3
)
2
2.30 (s, 3H, SMe), 1.90, 1.75 (2m, 2H, CH
2
-5), 1.86 (d, JMe,6 ¼ 1.3 Hz,
174.99 (C-2), 147.39 (C-7), 109.99 (C-6), 82.07
(C-3), 59.17 (OMe), 42.74 (C-4), 22.06 (Me-7), 20.99 (C-5), 11.86
13
3
H, Me-7); C NMR: d
4.3.6. 1-(Ethylsulfanyl)-2-methoxy-N-(1-methylethylidene)-1,3-
1
15
þ$
butadien-1-amine (4f)
(SMe); He N HMBC: ꢀ75.2; MS (EI, 70 eV) m/z ¼ 185 (59%) [M]
d
Brown mobile liquid. 1H NMR:
d
5.91 (dd,
3
3
J
J
trans ¼ 17.2 Hz,
trans ¼ 17.2 Hz,
[24a,b]. Anal. calcd for C H15NOS (185.29): C, 58.34; H, 8.16; N, 7.56;
9
3
J
J
cis ¼ 10.9 Hz, 1H, CH]), 5.20, 4.91 (2dd,
S, 17.31. Found: C, 58.19; H, 8.25; N, 7.65; S, 17.38.
3
3
3
2
cis ¼ 10.9 Hz, Jgem ¼ 1.9 Hz, 2H, CH
2
]), 3.63 (s, 3H, OMe), 2.58 (q,
J ¼ 7.3 Hz, 2H, SCH
2
CH
CH
33.82 (C-1), 126.49 (CH]), 110.07 (CH
3
), 2.15, 1.89 [2s, 6H, N]C(CH
3
)
2
], 1.23 (t,
173.39 (C]N), 138.75 (C-2),
]), 58.49 (OMe), 27.85,
4.4.1.2. 6-Methoxy-2-methyl-3H-azepine (2a). Yield: 2.10 g (38%)
13
J ¼ 7.3 Hz, 3H, SCH
2
3
); C NMR:
d
after rough separation on Al
Al [8a]; light-yellow liquid. IR (neat): 2970, 2943, 2909, 2875,
2830, 1620, 1536, 1456, 1427, 1390, 1371, 1338, 1292, 1219, 1155,
2 3
O ; 2.02 g (37%) after recleaning on
1
2
2 3
O
2
1.14 [N]C(CH
3
)
2
] 24.01 (SCH
2
CH
3
2 3
), 27.85, 15.19 (SCH CH ).
1
139, 1028, 999, 981, 952, 926, 897, 837, 755, 707, 629, 612,
ꢀ
1
1
4
4.3.7. 1-(Butylsulfanyl)-2-methoxy-N-(1-methylethylidene)-1,3-
557 cm
;
H NMR:
d
6.90 (d,
5,7 ¼ 2.5 Hz, 1H, H-5), 5.30 (dt,
4,2 ¼ 7.1 Hz, 1H, H-4), 3.65 (s, 3H, OMe), 2.48 (m, 2H, CH
J
7,5 ¼ 2.5 Hz, 1H, H-7), 6.16 (dd,
3
4
3
butadien-1-amine (4g)
J
J
5,4 ¼ 9.3 Hz,
J
J
4,5 ¼ 9.3 Hz,
-3), 2.10
150.36 (C-2), 147.82 (C-6), 124.58 (C-4),
Brown mobile liquid. 1H NMR:
cis ¼ 10.9 Hz, 1H, CH]), 5.20, 4.90 (2dd,
d
5.91 (dd,
3
J
J
trans ¼ 17.2 Hz,
trans ¼ 17.2 Hz,
3
2
3
3
3
3
13
J
J
(s, 3H, Me-2); C NMR:
d
2
cis ¼ 10.9 Hz, Jgem ¼ 1.8 Hz, 2H, CH
2
]), 3.63 (s, 3H, OMe), 2.55 (t,
121.14 (C-5), 118.00 (C-7), 56.02 (OMe), 37.23 (C-3), 25.55 (Me-2);
þ$
J ¼ 7.3 Hz, 2H, SCH
2
Pr), 2.15, 1.88 [2s, 6H, N]C(CH
3
)
2
], 1.55
MS (EI, 70 eV) m/z ¼ 137 (77%) [M] [24c]. Anal. calcd for C
8
H11NO
quintet, 3J ¼ 7.3 Hz, 2H, SCH
Et), 1.37 [sextet, J ¼ 7.3 Hz, 2H,
3
(137.18): C, 70.04; H, 8.08; N,10.21. Found: C, 70.19; H, 8.14; N,10.33.
(
2 2
CH
3
13
S(CH
2
)
2
CH
2
CH
3
], 0.88 [t, J ¼ 7.3 Hz, 3H, S(CH
2
)
3
CH
]), 58.53 (OMe), 32.40
Et), 27.91, 21.21 [N]C(CH ], 21.85
], 13.51 [S(CH CH ]. Signals of C-1 and C-2 groups
3
]; C NMR:
d
173.37 (C]N), 126.61 (CH]), 109.98 (CH
SCH Pr), 29.48 (SCH CH
S(CH CH CH
2
4.4.1.3. 1-Isopropyl-3-methoxy-2-(methylsulfanyl)pyrrole (5a). Yield:
(
[
2
2
2
3
)
2
0.73 g (10%) after rough separation on Al
recrystallisationfromlightpetroleum;light-yellowsolid;mp42e44 C. IR
2
O
3
[10a]; 0.37 g (5%) after
ꢁ
2
)
2
2
3
2
)
3
3
are not cumulated.
(KBr): 2969, 2926, 2873, 2834, 2672, 1570, 1561, 1539, 1459, 1411, 1396,
1
367, 1325, 1256, 1233, 1183, 1171, 1152, 1132, 1097, 1069, 1029, 959, 939,
ꢀ
1 1
4.4. General procedure 3: reaction of 2-aza-1,3,5-trienes 4aeg with
879, 834, 735, 687, 668, 652, 623, 598, 469, 423 cm ; H NMR:
d
6.65 (d,
4,5 ¼ 3.3 Hz, 1H, H-4), 4.73 [septet,
3 2
) ], 3.80 (s, 3H, OMe), 2.17 (s, 3H, SMe), 1.37 [d,
3
3
t-BuOK/THF/DMSO; synthesis of 4,5-dihydro-3H-azepines 1aeg and
J
5,4 ¼ 3.3 Hz, 1H, H-5), 5.89 (d,
J
3
3
3H-azepines 2aec, e
J ¼ 6.8 Hz, 1H, NCH(CH
J ¼ 6.8 Hz, 6H, NCH(CH
13
3 2
) ]; C NMR:
d
151.24 (C-3),116.16 (C-5), 105.21
], 23.71 [NCH(CH ],
e207.5; MS (EI, 70 eV) m/z ¼ 185 (100%)
15NOS (185.29): C, 58.34; H, 8.16; N, 7.56; S,
To a stirred solution of the 2-aza-1,3,5-triene 4 (23e43 mmol) in
(C-2), 94.59 (C-4), 58.12 (OMe), 46.80 [NCH(CH
)
3 2
3 2
)
1
15
THF (33e50 mL) a mixture of THF and DMSO (16e30 mL, 1:1, v/v)
20.89 (SMe); He N HMBC:
[M] [25]. Anal. calcd for C
d
ꢁ
þ$
and t-BuOK (1.15e1.48 equiv) were sequentially added at ꢀ65 C.
9
H
ꢁ
Reaction mixture was warmed to ꢀ30 C, stirred at this level for
17.31. Found: C, 58.22; H, 8.09; N, 7.49; S, 17.22.
ꢁ
3
0 min, then cooled to ꢀ60 C, quenched with H
2
O (w50 mL), and
extracted with Et
were washed with H
2
O (3 ꢂ 30 mL). The combined organic extracts
4.4.2. 2-Aza-1,3,5-triene 4b (39 mmol); t-BuOK (1.15 equiv); THF/
DMSO, 4:1
4.4.2.1. 3-Ethoxy-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-aze-
2
O (3 ꢂ 15 mL), dried (MgSO
4
) and concen-
ꢁ
trated under a reduced pressure at a bath temperature of 20 C. The
products were purified and separated in the following way. At first,
pine (1b). Yield: 1.75 g (23%) after rough separation on Al
2
O
3
; 1.63 g
2
2
by column chromatography on neutral Al
2
O
3
(light petroleum and
(21%) after separation with HCl; colourless oil; n 1.5080. IR (neat):
D
light petroleumeEt O, 10:1, 3:1) were obtained two fractions con-
2
2975, 2957, 2923, 2868, 1632, 1575, 1478, 1444, 1402, 1375, 1343,
1332, 1312, 1243, 1218, 1177, 1142, 1112, 1083, 1057, 1038, 1006, 976,
sisting mostly of azepine 2 and a mixture of dihydroazepine 1 with
pyrrole 5. Then, the fraction containing azepine 2 was repetitively
purified by column chromatography. The fraction containing
compounds 1 and 5 (the ethereal solution) was vigorously shaken
for few sec with a calculated amount of a w3e8% solution of
ꢀ
1 1
916, 896, 874, 785, 727, 705, 587, 565, 529, 455 cm ; H NMR: d 5.18
3
3
3
(ddq, J ¼ 7.8 Hz, J ¼ 5.3 Hz, 1H, H-6), 4.09 (dd, J ¼ 10.6 Hz,
3
2
J ¼ 7.8 Hz,1H, H-3), 3.60, 3.40 (2dq, J ¼ 8.9 Hz, 2H, OCH
2
3
CH ), 2.43,
2.10 (2m, 2H, CH
2
-5), 2.29 (s, 3H, SMe),1.91,1.74 (2m, 2H, CH
2
-4),1.86

3366
N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
4
3
); 13C NMR:
3J4,3 ¼ 7.2 Hz,1H, H-4), 4.18 [septet, J ¼ 6.1 Hz,1H, OCH(CH
3
(
d
d, J ¼ 1.2 Hz, 3H, Me-7),1.21 (t, J ¼ 7.0 Hz, 3H, OCH
2
CH
3
3 2
) ], 2.50
3
175.49 (C-2), 147.11 (C-7), 109.72 (C-6), 79.76 (C-3), 66.79
OCH
(m, 2H, CH
2
-3), 2.12 (s, 3H, Me-2), 1.22 [d, J ¼ 6.1 Hz, 6H,
13
(
(
[
2
CH
3
), 42.79 (C-5), 21.86 (Me-7), 20.86 (C-4),15.01 (SMe),11.68
OCH(CH
3 2
) ]; C NMR: d 147.71 (C-6), 147.33 (C-2), 127.03 (C-7),
1
15
OCH
2
CH
3
); He N HMBC:
d
ꢀ75.6; MS (EI, 70 eV) m/z ¼ 199 (31%)
125.46 (C-5), 117.22 (C-4), 71.91 [OCH(CH
3
)
2
], 37.51 (C-3), 26.36
þ$
þ$
M] [24b]. Anal. calcd for C10
H
17NOS (199.31): C, 60.26; H, 8.60; N,
(Me-2), 22.09 [OCH(CH
[24c]. Anal. calcd for C10
3
)
H
2
]; MS (EI, 70 eV) m/z ¼ 165 (51%) [M]
7
.03; S, 16.09. Found: C, 60.05; H, 8.49; N, 7.15; S, 16.22.
15NO (165.23): C, 72.69; H, 9.15; N, 8.48.
Found: C, 72.48; H, 9.09; N, 8.71.
4
.4.2.2. 6-Ethoxy-2-methyl-3H-azepine (2b). Yield: 2.03 g (34%)
; 2.01 g (34%) after recleaning on
1.5075. IR (neat): 2977, 2939, 2910, 2873, 2824,
619, 1531, 1479, 1431, 1390, 1371, 1339, 1290, 1242, 1217, 1206, 1171,
after rough separation on Al
Al
1
2
O
3
4.4.3.3. 3-Isopropoxy-1-isopropyl-2-(methylsulfanyl)pyrrole
(5c).
; liquid; n2
2
Yield: 0.52 g (6%) after rough separation on Al
D
recleaning on Al ; light-yellow mobile liquid; n 1.5044. H NMR:
2
O
3
D
2 3
O ; 0.27 g (3%) after
2
2
1
2
O
3
3
3
1
150, 1114, 1088, 1045, 990, 949, 934, 910, 891, 859, 847, 821, 755,
d
6.62 (d, J5,4 ¼ 3.3 Hz, 1H, H-5), 5.84 (d, J4,5 ¼ 3.3 Hz, 1H, H-4), 4.73
ꢀ
1
1
3
3
7
J
30, 701, 640, 625, 613, 562, 475, 440 cm ; H NMR:
d
6.95 (d,
[septet, J ¼ 6.8 Hz, 1H, OCH(CH
NCH(CH
3
)
2
], 4.29 [septet, J ¼ 6.1 Hz, 1H,
4
4
3
7,5 ¼ 2.2 Hz, 1H, H-7), 6.19 (dd,
J
5,7 ¼ 2.2 Hz, 1H, H-5), 5.34 (dt,
3
)
2
], 2.16 (s, 3H, SMe), 1.36 [d, J ¼ 6.8 Hz, 6H, OCH(CH
3 2
) ], 1.31
3J4,5 ¼ 9.2 Hz,
3
J
4,3 ¼ 7.1 Hz, 1H, H-4), 3.87 (q, J ¼ 7.0 Hz, 2H,
3
3
13
[d, J ¼ 6.1 Hz, 6H, NCH(CH
115.99 (C-5), 97.30 (C-4), 73.22 [OCH(CH
[OCH(CH ], 22.37 [NCH(CH
], 20.60 (SMe); MS (EI, 70 eV) m/z ¼ 213
(64%) [M] [25]. Anal. calcd for C11 19NOS (213.34): C, 61.93; H, 8.98;
3 2
) ]; C NMR: d
148.97 (C-3), 147.15 (C-2),
3
OCH
2
CH
3
), 2.50 (d, J ¼ 5.0 Hz, 2H, CH
2
-3), 2.12 (s, 3H, Me-2), 1.31 (t,
149.45 (C-6), 147.59 (C-2),
24.88 (C-7), 122.61 (C-5), 117.74 (C-4), 64.41 (OCH CH ), 37.26 (C-
); MS (EI, 70 eV) m/z ¼ 151 (44%)
13NO (151.21): C, 71.49; H, 8.67; N,
3
)
2
], 46.71 [NCH(CH ], 23.62
3 2
)
3
13
J ¼ 7.0 Hz, 3H, OCH
2
CH
3
); C NMR:
d
3
)
2
3 2
)
þ$
1
2
3
H
3
), 26.49 (Me-2), 14.97 (OCH
2
CH
3
N, 6.57; S, 15.03. Found: C, 61.79; H, 8.80; N, 6.43; S, 15.18.
þ∙
[
M] [24c]. Anal. calcd for C
9
H
9
.26. Found: C, 71.20; H, 8.61; N, 9.45.
4.4.4. 2-Aza-1,3,5-triene 4d (40 mmol); t-BuOK (1.28 equiv); THF/
DMSO, 4:1
4.4.2.3. 3-Ethoxy-1-isopropyl-2-(methylsulfanyl)pyrrole (5b). Yield:
4.4.4.1. 3-(tert-Butoxy)-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-
2
.14 g (28%) after rough separation on Al ; 1.20 g (15%) after
2
O
3
azepine (1d). Yield: 2.79 g (31%) after rough separation on Al
2 3
O ;
21
recrystallisation from light petroleum and recleaning on Al
colourless crystallizing liquid; n
2
O
3
;
1.20 g (13%) after 2-fold purification on Al ; colourless liquid; n
O
2 3
D
2
2
D
1.5044. IR (neat): 2975, 2919,
1.4944. IR (neat): 2975, 2942, 2923, 2877, 2856, 1632, 1574, 1469,
1446, 1433, 1413, 1389, 1366, 1347, 1336, 1311, 1256, 1236, 1193, 1181,
1138, 1095,1085,1063, 1037, 1023,1006, 982, 963, 917, 898, 872, 800,
2
874, 2824, 1546, 1478, 1455, 1415, 1400, 1384, 1367, 1320, 1291,
1270, 1225, 1165, 1128, 1112, 1102, 1089, 1070, 1033, 994, 964, 896,
ꢀ
1
1
ꢀ1 1
8
75, 812, 709, 664, 619, 590, 491 cm
;
H NMR:
d
6.63 (d,
785, 760, 727, 706, 676, 592, 535, 510, 488, 456, 443 cm ; H NMR:
3
3
3
3
4
J
5,4 ¼ 3.3 Hz, 1H, H-5), 5.87 (d, J4,5 ¼ 3.3 Hz, 1H, H-4), 4.73 [septet,
d
5.20 (ddq, J ¼ 7.9 Hz, J ¼ 5.2 Hz, J ¼ 1.0 Hz, 1H, H-6), 4.31 (dd,
3
3
3 3
J ¼ 6.9 Hz, 1H, NCH(CH
3
)
2
], 4.02 (q, J ¼ 7.1 Hz, 2H, OCH
2
CH
3
), 2.17
), 1.37 [d, J ¼ 6.9 Hz,
150.12 (C-3), 116.06 (C-5), 105.90 (C-2),
5.69 (C-4), 66.50 (OCH CH ), 46.79 [NCH(CH ], 23.71
), 15.24 (SMe); MS (EI, 70 eV) m/
17NOS (199.31): C,
J ¼ 11.0 Hz, J ¼ 8.2 Hz, 1H, H-3), 2.27 (s, 3H, SMe), 2.24, 2.11 (2m,
3
3
4
(
s, 3H, SMe), 1.37 (t, J ¼ 7.1 Hz, 3H, OCH
2
CH
3
2H, CH
1.17 [s, 9H, OC(CH
(C-6), 75.06 [OC(CH
2
-5), 1.87 (d, J ¼ 1.0 Hz, 3H, Me-7), 1.87, 1.73 (2m, 2H, CH
2
-4),
177.54 (C-2), 147.14 (C-7), 109.79
], 71.94 (C-3), 44.83 (C-5), 27.48 [OC(CH ],
1
3
13
6
9
H, NCH(CH
3
)
2
]; C NMR:
d
3 3
) ]; C NMR: d
2
3
3
)
2
)
3 3
3 3
)
[
NCH(CH
3
)
2
], 20.80 (OCH
2
CH
3
22.00 (Me-7), 21.15 (C-4),12.10 (SMe); MS (EI, 70 eV) m/z ¼ 227 (13%)
þ$
þ$
z ¼ 199 (100%) [M] [25]. Anal. calcd for C10
H
[M] [24b]. Anal. calcd for C12
H21NOS (227.37): C, 63.39; H, 9.31; N,
6
0.26; H, 8.60; N, 7.03; S, 16.09. Found: C, 60.01; H, 8.78; N, 7.21; S,
6.16; S, 14.10. Found: C, 63.22; H, 9.18; N, 6.11; S, 14.35.
15.88.
4
.4.4.2. 3-(tert-Butoxy)-1-isopropyl-2-(methylsulfanyl)pyrrole (5d).
21
4
.4.3. 2-Aza-1,3,5-triene 4c (43 mmol); t-BuOK (1.19 equiv); THF/
DMSO, 4:1
.4.3.1. 3-Isopropoxy-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-
2 3
azepine (1c). Yield: 5.37 g (57%) after rough separation on Al O ;
2 3 D
Yield: 1.33 g (15%) after rough separation on Al O ; liquid; n 1.4880.
IR (neat): 2975, 2922, 2874, 2827, 1630, 1576, 1525, 1477, 1455, 1421,
1410, 1385, 1364, 1321, 1275, 1259, 1240, 1219, 1180, 1130, 1119, 1079,
1057, 1031, 1021, 996, 966, 917, 879, 824, 776, 751, 734, 657, 638, 626,
4
ꢀ
1
1
3
4
.98 g (53%) after 2-fold purification on Al
2
O
3
; colourless mobile
573, 512, 460, 416 cm ; H NMR:
d
6.62 (d, J5,4 ¼ 3.1 Hz, 1H, H-5),
19
3
3
liquid; n
D
1.4993. IR (neat): 2970, 2943, 2923, 2881, 2858, 1632,
5.88 (d,
NCH(CH
1.33 [s, 9H, OC(CH
(C-2), 103.35 (C-4), 78.03 [OC(CH
[OC(CH ], 23.74 [NCH(CH
], 20.43 (SMe); MS (EI, 70 eV) m/z ¼ 227
(12%) [M] [25]. Anal. calcd for C12 21NOS (227.37): C, 63.39; H,
J
4,5 ¼ 3.1 Hz, 1H, H-4), 4.73 [septet, J ¼ 6.9 Hz, 1H,
3
1573, 1465, 1445, 1413, 1376, 1327, 1311, 1245, 1176, 1144, 1124, 1098,
3
)
2
], 2.16 (s, 3H, SMe), 1.36 [d, J ¼ 6.9 Hz, 6H, NCH(CH
3
)
2
],
144.93 (C-3), 115.77 (C-5), 112.80
], 47.11 [NCH(CH ], 28.75
13
1
7
1
059, 1039, 1005, 982, 958, 938, 926, 912, 887, 830, 799, 785, 727,
3 3
) ]; C NMR: d
ꢀ
1 1
08, 677, 589, 573, 531, 494, 468, 447, 417 cm ; H NMR:
d
5.19 (m,
3
)
3
3 2
)
3
3
H, H-6), 4.19 (dd, J ¼ 10.6 Hz, J ¼ 7.8 Hz, 1H, H-3), 3.56 [septet,
3
)
3
3 2
)
3
þ$
J ¼ 6.1 Hz, 1H, OCH(CH
3
)
2
], 2.34, 2.10 (2m, 2H, CH
2
-5), 2.28 (s, 3H,
H
SMe), 1.91, 1.73 (2m, 2H, CH
2
-4), 1.86 (br s, 3H, Me-7), 1.22, 1.09 [2d,
9.31; N, 6.16; S, 14.10. Found: C, 63.54; H, 9.22; N, 6.05; S, 14.25.
3
13
J ¼ 6.1 Hz, 6H, OCH(CH
3
)
2
]; C NMR:
d
176.17 (C-2), 147.11 (C-7),
], 43.55 (C-5), 22.55,
1
09.82 (C-6), 77.06 (C-3), 72.02 [OCH(CH
3
)
2
4.4.5. 2-Aza-1,3,5-triene 4e (36 mmol); t-BuOK (1.31 equiv); THF/
DMSO, 4:1
2
1.08 [OCH(CH
3
)
2
], 21.98 (Me-7), 21.04 (C-4), 11.92 (SMe); MS (EI,
þ$
7
0 eV) m/z ¼ 213 (44%) [M] [24b]. Anal. calcd for C11
H19NOS
4.4.5.1. 3-(Allyloxy)-7-methyl-2-(methylsulfanyl)-4,5-dihydro-3H-
azepine (1e). Yield: 1.96 g (26%) after separation with HCl; colour-
(
213.34): C, 61.93; H, 8.98; N, 6.57; S, 15.03. Found: C, 61.82; H, 8.97;
19
N, 6.82; S, 15.23.
less mobile liquid; n
D
1.5188. IR (neat): 2976, 2943, 2923, 2859,1646,
1632, 1574, 1447, 1438, 1428, 1411, 1376, 1345, 1332, 1312, 1268, 1244,
4
.4.3.2. 6-Isopropoxy-2-methyl-3H-azepine (2c). Yield: 1.34 g (18%)
after rough separation on Al ; 1.16 g (16%) after recleaning on
Al ; red-brown mobile liquid; n
875, 2824, 1617, 1578, 1527, 1465, 1427, 1414, 1381, 1370, 1356,
1178, 1140, 1104, 1093, 1066, 1037, 1008, 994, 967, 926, 885, 785, 727,
ꢀ
1
1
3
2
O
3
714, 680, 638, 586, 559, 530 cm ; H NMR:
d
5.90 (dddd, J ¼ 17.3 Hz,
2
0
3
3
2
O
3
D
1.4996. IR (neat): 2974, 2933,
J ¼ 10.6 Hz, 1H, OCH
2
CH]CH
J ¼ 10.6 Hz, J ¼ 1.0 Hz, 2H, OCH
2
), 5.28, 5.18 (2d, J ¼ 17.3 Hz,
3
2
2
2
CH]CH
2
), 5.18 (m, 1H, H-3), 4.15
3
3
2
1288, 1242, 1205, 1167, 1139, 1114, 992, 932, 897, 837, 825, 764, 754,
(dd, J ¼ 7.8 Hz, J ¼ 10.5 Hz, 1H, H-6), 4.14, 3.86 (dd, J ¼ 12.7 Hz,
ꢀ
1
1
4
3
718, 644, 626, 611, 563 cm ; H NMR:
d
7.05 (d, J7,5 ¼ 2.2 Hz, 1H,
2 2 2
J ¼ 6.1 Hz,1H, OCH CH]CH ), 2.44, 2.13 (2m, 2H, CH -5), 2.30 (s, 3H,
4
3
13
H-7), 6.19 (dd,
J
5,7 ¼ 2.2 Hz, 1H, H-5), 5.32 (dt,
J
4,5 ¼ 9.2 Hz,
SMe),1.90,1.75 (2m, 2H, CH
2
-4),1.85 (s, 3H, Me-7); C NMR: d 174.96

N.A. Nedolya et al. / Journal of Organometallic Chemistry 696 (2011) 3359e3368
3367
3
(
1
(
C-2), 147.09 (C-7), 133.99 (OCH
09.72 (C-6), 79.08 (C-3), 71.82 (OCH
2
CH]CH
2
), 117.06 (OCH
2
CH]CH
2
),
[septet, J ¼ 6.8 Hz, 1H, NCH(CH
3
)
2
], 3.78 (s, 3H, OMe), 2.54 (q,
3
3
2
CH]CH
2
), 42.72 (C-5), 21.83
J ¼ 7.4 Hz, 2H, SCH
2
CH
(t, J ¼ 7.4 Hz, 3H, SCH CH
103.30 (C-2), 94.37 (C-4), 57.82 (OMe), 46.31 [NCH(CH
(SCH CH ), 23.44 [NCH(CH ], 14.37 (SCH CH ). Anal. calcd for
17NOS (199.31): C, 60.26; H, 8.60; N, 7.03; S, 16.09. Found: C,
3
), 1.35 [d, J ¼ 6.8 Hz, 6H, NCH(CH
3
)
2
], 1.15
151.78 (C-3), 116.00 (C-5),
], 31.00
þ$
3
13
Me-7), 20.83 (C-4), 11.71 (SMe); MS (EI, 70 eV) m/z ¼ 211 (5%) [M]
2
3
); C NMR: d
[24b]. Anal. calcd for C11
H17NOS (211.32): C, 62.52; H, 8.11; N, 6.63; S,
3 2
)
1
5.17. Found: C, 62.64; H, 8.23; N, 6.45; S, 15.28.
2
3
3
)
2
2
3
10
C H
4
.4.5.2. 6-(Allyloxy)-2-methyl-3H-azepine (2e). Yield: 1.82 g (31%)
60.34; H, 8.71; N, 6.91; S, 16.19.
19
after separation with HCl; yellow mobile liquid; n
D
1.5243. IR
(
1
1
neat): 2973, 2940, 2912, 2875, 2826, 1648, 1620, 1596, 1533, 1456,
420, 1371, 1341, 1291, 1271, 1243, 1213, 1205, 1169, 1107, 1090, 1020,
4.4.7. 2-Aza-1,3,5-triene 4g (29 mmol); t-BuOK (1.48 equiv); THF/
DMSO, 4.5:1
4.4.7.1. 2-(Butylsulfanyl)-3-methoxy-7-methyl-4,5-dihydro-3H-aze-
ꢀ
1
1
002, 929, 866, 837, 821, 760, 744, 705, 653, 618, 556 cm
;
H
4
4
NMR:
5
d
6.98 (d, J7,5 ¼1.4 Hz, 1H, H-7), 6.21 (dd, J5,7 ¼ 1.4 Hz, 1H, H-
pine (1g). Yield: 2.36 g (36%) after rough separation on Al
2 3
O ;
3
3
25
), 5.97 (ddt,
J
trans ¼ 17.2 Hz,
J
cis ¼ 10.5 Hz, 1H, OCH
2
CH]CH
2
),
1.91 g (29%) after separation with HCl; yellow mobile liquid; n
D
.35 (d, 3
J
4,5 ¼ 9.3 Hz, 1H, H-4), 5.33, 5.21 (2d,
3
J
trans ¼ 17.2 Hz,
1.5154. IR (neat): 2956, 2929, 2873, 2859, 2825, 1632, 1597, 1571,
1543, 1463, 1453, 1439, 1404, 1377, 1349, 1337, 1310, 1299, 1275,
1247, 1228, 1208, 1175, 1137, 1113, 1083, 1057, 1036, 1005, 963, 940,
5
3
3
4
J
cis ¼ 10.5 Hz, 2H, OCH
H, OCH CH]CH ), 2.49 (m, 2H, CH
NMR: 148.87 (C-2), 147.39 (C-6), 133.38 (OCH
C-5), 123.09 (C-7), 117.54 (C-4), 117.18 (OCH
2
CH]CH
2
), 4.35 (dt, J ¼ 5.5 Hz, J ¼ 1.2 Hz,
1
3
2
2
2
2
-3), 2.11 (s, 3H, Me-2);
CH]CH ), 124.46
CH]CH ), 69.77
), 37.09 (C-3), 26.24 (Me-2); MS (EI, 70 eV) m/z ¼ 163
13NO (163.22): C, 73.59; H,
C
ꢀ
1 1
d
2
2
916, 885, 798, 785, 745, 728, 699, 678, 647, 586, 530, 449 cm ; H
3
3
4
(
(
(
2
2
NMR:
6), 3.99 (dd,
d
5.17 (ddq, J6,5’ ¼ 7.8 Hz, J6,5 ¼ 5.4 Hz, J6,Me ¼ 1.2 Hz, 1H, H-
3 3
OCH
2
CH]CH
2
J
3,4’ ¼ 10.4 Hz,
J
3,4 ¼ 7.8 Hz, 1H, H-3), 3.38 (s, 3H,
þ$
2
3
15%) [M] [24c]. Anal. calcd for C10
H
OMe), 2.97, 2.92 (dt, J ¼ 12.9 Hz, J ¼ 7.3 Hz, 1H, SCH
2
4
Pr), 2.47, 2.08
8
.03; N, 8.58. Found: C, 73.39; H, 8.18; N, 8.64.
(2m, 2H, CH
3
2
-5), 1.92, 1.74 (2m, 2H, CH
2
-4), 1.85 (d, JMe,6 ¼ 1.4 Hz,
3
H, Me-7), 1.63 (m, 2H, SCH CH
2
2
Et), 1.44 [sextet, J ¼ 7.4 Hz, 2H,
3
13
4
.4.5.3. 3-(Allyloxy)-1-isopropyl-2-(methylsulfanyl)pyrrole
(5e).
S(CH
2
)
2
CH
2
CH
3
], 0.92 [t, J ¼ 7.4 Hz, 3H, S(CH
2 3 3
) CH ]; C NMR:
Yield: 1.20 g (16%) after separation with HCl; 0.62 g (8%) after
recleaning on Al
2
1
d
174.09 (C-2), 147.24 (C-7), 109.53 (C-6), 81.82 (C-3), 58.88 (OMe),
42.56 (C-5), 30.77 (SCH CH Et), 27.94 (SCH Pr), 22.09
[S(CH CH CH ], 21.82 (Me-7), 20.84 (C-4), 13.64 [S(CH CH ].
Anal. calcd for C12 21NOS (227.37): C, 63.39; H, 9.31; N, 6.16; S,
14.10. Found: C, 63.58; H, 9.42; N, 6.37; S, 14.23.
2
2
2
O
3
; light-yellow liquid; n
D
1.5150. IR (neat): 2975,
2
2
2
920, 2873, 1647, 1602, 1545, 1455, 1416, 1396, 1388, 1368, 1320, 1289,
270, 1219, 1130, 1090, 1067, 1014, 995, 966, 925, 877, 814, 709, 667,
2
)
2
2
3
2
)
3
3
H
ꢀ
1
1
3
6
20, 589, 566, 472 cm
;
H NMR:
d
6.62 (d, J ¼ 3.2 Hz, 1H, H-5),
3
3
6
.05 (ddt, Jtrans ¼ 17.4 Hz, Jcis ¼ 10.5 Hz, 1H, OCH
2 2
CH]CH ), 5.86 (d,
3
3
3
J ¼ 3.2 Hz, 1H, H-4), 5.36, 5.20 (ddt, Jtrans ¼ 17.4 Hz, Jcis ¼ 10.5 Hz,
4.4.7.2. 6-Methoxy-2-methyl-3H-azepine (2a). Yield: 0.56 g (14%)
2
4
3
J z Jgem ¼ 1.3 Hz, 2H, OCH
2
CH]CH
2
), 4.73 [septet, J ¼ 6.7 Hz, 1H,
2 3
after rough separation on Al O . The compound protocol see above
3
4
NCH(CH
3
)
2
], 4.50 (dt, J ¼ 5.4 Hz, J ¼ 1.3 Hz, 2H, OCH
2 2
CH]CH ), 2.17
(Section 4.4.1.2).
3
13
(
(
1
2
s, 3H, SMe), 1.36 [d, J ¼ 6.7 Hz, 6H, NCH(CH
C-3), 134.25 (OCH CH]CH ), 116.87 (C-5), 115.86 (OCH
05.06 (C-2), 95.86 (C-4), 71.73 (OCH CH]CH ), 46.65 [NCH(CH
3.54 [NCH(CH
], 20.61 (SMe); MS (EI, 70 eV) m/z ¼ 211 (23%) [M]
25]. Anal. calcd for C11 17NOS (211.32): C, 62.52; H, 8.11; N, 6.63; S,
5.17. Found: C, 62.38; H, 8.19; N, 6.51; S, 15.02.
3
)
2
]; C NMR:
d
149.76
),
],
2
2
2
CH]CH
2
4.4.7.3. 2-(Butylsulfanyl)-1-isopropyl-3-methoxypyrrole (5g). Yield:
0.79 g (12%) after rough separation on Al ; brown mobile liquid.
2
2
3
)
2
2 3
O
þ$
1
3
3
3
)
2
H NMR:
d
6.66 (d, J5,4 ¼ 3.2 Hz, 1H, H-5), 5.90 (d, J4,5 ¼ 3.2 Hz, 1H,
3
[
H
H-4), 4.76 [septet, J ¼ 6.7 Hz, 1H, NCH(CH
3 2
) ], 3.79 (s, 3H, OMe),
3
1
4
2.68 (m, 2H, SCH
2
Pr), 1.76 (quintet, J ¼ 7.3 Hz, 2H, SCH
2
CH
], 1.35 [d, J ¼ 6.7 Hz, 6H,
], 0.88 [t, J ¼ 7.3 Hz, 3H, S(CH CH ]. Anal. calcd for
2
Et), 1.54
3
3
[
sextet, J ¼ 7.3 Hz, 2H, S(CH
2 2 2 3
) CH CH
3
.4.6. 2-Aza-1,3,5-triene 4f (23 mmol); t-BuOK (1.43 equiv); THF/
NCH(CH
3
)
2
2
)
3
3
DMSO, 5:1
.4.6.1. 2-(Ethylsulfanyl)-3-methoxy-7-methyl-4,5-dihydro-3H-aze-
pine (1f). Yield: 1.75 g (38%) after rough separation on Al ; 1.57 g
1.5259. IR
neat): 2968, 2927, 2858, 2825, 2726, 1632, 1572, 1511, 1451, 1439,
409, 1374, 1349, 1337, 1310, 1299, 1267, 1247, 1208, 1175, 1138, 1113,
12
C H21NOS (227.37): C, 63.39; H, 9.31; N, 6.16; S, 14.10. Found: C,
4
63.17; H, 9.40; N, 6.19; S, 14.31.
2 3
O
2
5
(
34%) after separation with HCl; yellow mobile liquid; n
D
Acknowledgments
(
1
1
The authors are grateful for the financial support to the Russian
Foundation for Basic Research (Grant No. 09-03-00890a) and the
Presidium of the Russian Academy of Sciences (Project No. 7.20).
084,1056,1037,1004, 963, 914, 886, 798, 786, 749, 720, 701, 680, 647,
ꢀ
1
1
3
3
5
86, 528, 447 cm ; H NMR:
J
d
5.18 (ddq, J6,5’ ¼ 7.8 Hz, J6,5 ¼ 5.4 Hz,
4
3 3
6,Me ¼ 1.4 Hz,1H, H-6), 3.99 (dd, J3,4’ ¼ 10.4 Hz, J3,4 ¼ 7.8 Hz,1H, H-
2 3
3
), 3.37 (s, 3H, OMe), 2.96, 2.91 (dq, J ¼ 13.1 Hz, J ¼ 7.4 Hz, 1H,
SCH CH ), 2.47, 2.08 (2m, 1H, CH -4), 1.91, 1.74 (2m, 2H, CH -5), 1.85
2d, JMe,6 ¼ 1.4 Hz, 3H, Me-7), 1.29 (t, J ¼ 7.4 Hz, 3H, SCH
NMR: 173.97 (C-2), 147.25 (C-7), 109.59 (C-6), 81.75 (C-3), 58.88
OMe), 42.56 (C-5), 22.63 (SCH CH ), 21.79 (Me-7), 20.81 (C-4),13.78
SCH CH ). Anal. calcd for C10 17NOS (199.31): C, 60.26; H, 8.60; N,
.03; S, 16.09. Found: C, 60.15; H, 8.64; N, 7.19; S, 16.00.
References
2
3
2
2
CH
4
3
13
(
2
3
);
C
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d
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(
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2
3
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(
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(
Section 4.4.1.2).
(
4
0
.4.6.3. 2-(Ethylsulfanyl)-1-isopropyl-3-methoxypyrrole (5f). Yield:
(
.85 g (19%) after rough separation on Al ; 0.53 g (12%) after
2 3
O
1
separation with HCl; yellow mobile liquid. H NMR:
d
6.67 (d,
(
3
3
J5,4 ¼ 3.3 Hz, 1H, CH-5), 5.91 (d,
J
4,5 ¼ 3.3 Hz, 1H, CH-4), 4.76

3368
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(
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(
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