Reactions of N-and C-alkenylanilines: X.* Synthesis of 2-vinyldihydroindoles from 4-methyl-2-(pent-3-en-2-yl)aniline

Article abstract of DOI:10.1134/S1070428012090096

2-(1-Iodoethyl)-3,5-dimethyl-1-(4-methylphenylsulfonyl)-2, 3-dihydro-1H-indole reacted with pyridine, piperidine, N-alkylpiperidines, and dimethylformamide to give dehydrohalogenation and halogen substitution products whose ratio depended on the reagent s

Full text of DOI:10.1134/S1070428012090096

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 9, pp. 1200–1209. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © G.G. Mazgarova, A.M. Absalyamova, R.R. Gataullin, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 9,
pp. 1201–1210.
Reactions of N- and C-Alkenylanilines: X.* Synthesis
of 2-Vinyldihydroindoles from 4-Methyl-2-(pent-3-en-2-yl)aniline
G. G. Mazgarova, A. M. Absalyamova, and R. R. Gataullin
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: gataullin@anrb.ru
Received December 8, 2011
Abstract—2-(1-Iodoethyl)-3,5-dimethyl-1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-indole reacted with pyri-
dine, piperidine, N-alkylpiperidines, and dimethylformamide to give dehydrohalogenation and halogen sub-
stitution products whose ratio depended on the reagent structure. Heating of 2-(1-iodoethyl)-3,5-dimethyl-1-
methylsulfonyl-2,3-dihydro-1H-indole with piperidine resulted in the formation of only dehydroiodination
products.
DOI: 10.1134/S1070428012090096
isolated from the mother liquor by chromatography on
silica gel; it was a viscous material containing up to
10% of unidentified impurity. trans Isomer IIb also
predominated among the cyclization products obtained
from o-nitrobenzenesulfonyl analog IIIb; however, we
failed to separate it from cis isomer Ib by crystalliza-
tion from ethanol. Therefore, coupling constants for
the 2-H, 3-H, and 1′-H protons and methyl protons in
Vinylindole derivatives attract researchers’ attention
as starting materials for the synthesis of a number of
heterocyclic compounds. Apart from functionalization
at the olefinic fragment, vinylindoles are used in the
synthesis of carbazole derivatives with different
degrees of hydrogenation [2–4], pyrrolo[1,2-a]indoles
[5, 6], and tetracyclic core of lundurine alkaloids
exhibiting antitumor activity [7].
1
minor isomer Ib were determined from the H NMR
2,3-Dihydroindoles having a vinyl fragment in the
2-position are generally obtained by cyclization of
o-allylaniline in the presence of metal complex cata-
lysts on the basis of mercury or palladium salts [8–10]
or organotin compounds [7].
spectrum of isomer mixture enriched in that isomer.
Isomeric dihydroindoles Ic and IIc were separated by
chromatography on silica gel.
Heating of trans isomer IIa in boiling piperidine
resulted in the formation of a mixture of dehydro-
iodination products V and VI and halogen substitution
product VII (see table) in an overall yield of 78%.
Compound VII was converted into hydrochloride VIII
by treatment with a solution of HCl; hydrochloride
VIII is readily soluble in methylene chloride and
ethanol but sparingly soluble in water, so that it can be
isolated together with heterocycles V and VI. The
latter crystallized from a solution in ethanol on
cooling, while hydrochloride VIII remained in the
filtrate (Scheme 2). After removal of the solvent, hy-
drochloride VIII containing small impurities of com-
pounds V and VI was dissolved in methylene chloride,
and the solution was treated with a saturated solution
of NaHCO3 to precipitate base VII containing 4% of V
and VI. Recrystallization gave analytically pure com-
pound VII, and pure hydrochloride VIII was isolated
In the present article we describe the synthesis of
2-vinylindole derivatives from iodocyclization prod-
ucts I and II. The C1′, C2, and C3 atoms in the resulting
dihydroindoles were assigned (S*)- or (R*)-configura-
tion on the basis of the assumed iodocyclization
mechanism which implies formation of iodonium
intermediates A or B with different orientations of the
methyl group on C1′. Intramolecular nucleophilic (SN2)
attack by the nitrogen atom on C2′ in A and B leads to
stereoisomeric dihydroindoles I and II differing by
configuration of C3 (Scheme 1).
trans Isomer IIa was formed as the major product,
and it can readily be separated from cis isomer Ia by
recrystallization from ethanol. cis Isomer Ia was
* For communication IX, see [1].
1200

REACTIONS OF N- AND C-ALKENYLANILINES: X.
1201
Scheme 1.
Me
Me
R3SO2Cl
PhH, Et3N
R2
R2
Me
Me
NH2
NHSO2R3
R1
R1
IVa, IVc
IIIa–IIIc
Me
I+
I+
Me
R2
R2
I2, NaHCO3
CH2Cl2
Me
Me
I–
+
I–
NHSO2R3
NHSO2R3
R1
R1
A
B
Me
Me
R2
R2
H
Me
H
Me
I
3
1'
2
+
I
N
N
H
H
SO2R3
SO2R3
R1
R1
Ia–Ic
IIa–IIc
Ratio Ia/IIa 1:5, Ib/IIb 1:5, Ic/IIc 1:1;
R1 = H, R2 = Me, R3 = 4-MeC6H4 (a), 2-O2NC6H4 (b); R1 = Me, R2 = H, R3 = 4-MeC6H4 (c).
Scheme 2.
Me
Me
Me
Me
N
Me
R
Me
Me
Me
CH2
H
Me
I
H
Me
H
N
reflux
+
+
Me
N
N
N
N
H
H
Ts
Ts
Ts
Ts
IIa
V
VI
VII
Me
Me
H
N
HCl, CCl4, 20°C
VII
· HCl
Me
N
H
Ts
VIII
Me
Me
Me
Me
I–
H
H
N
N
, reflux
N
NaBH4, EtOH
IIa
Me
Me
N
N
H
H
Ts
Ts
IX
X
from methyl protons and signals from the aliphatic
fragment into broadened singlets. The conjugate acid
proton signal was observed at δ 12.2 ppm.
With a view to avoid formation of amine VII, com-
pound IIa was heated in boiling N-methylpiperidine.
as a viscous material (yield 89%) by bubbling hydro-
gen chloride through a solution of VII in carbon tetra-
chloride. The presence of an ammonium fragment in
molecule VIII impairs resolution of signals in the
1H NMR spectrum up to transformation of doublets
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

MAZGAROVA et al.
1202
Scheme 3.
Me
Me
Me
Me
H
OCHO
Me
H
I
Me2NCHO, reflux
IIa
+
Me
N
N
H
H
Ts
Ts
XI
XII
H
I–
Me
Me
O
Me
Me
NMe2
Me
Me
Me
H
H
O
CH=NMe2
H
Me
IIa
+
Me
I
I
I–
N
N
N
H
H
H
Ts
Ts
Ts
C
D
E
H2O –Me2NH·HI
XI
XII
The reaction was complete in 30 h, and vinyl deriva-
tive V was isolated in 80% yield (after crystallization
from ethanol), whereas no isomer VI was present.
Analogous transformation of IIa in N-propylpiperidine
required considerably shorter time, the yield of dehy-
drohalogenation product V being approximately the
same (see table).
When compound IIa was heated in boiling DMF,
only halogen substitution product was formed, whereas
dehydrohalogenation products were not detected.
Chromatographic separation of the product mixture on
silica gel gave formic acid ester XI and (assumingly)
(1′R*)-isomer XII (~20%; Scheme 3). Presumably,
ester XI is formed following the reaction sequence
IIa→C→D which includes replacement of the halo-
gen atom by quaternary salt fragment and hydrolysis to
ester XI. Compound XII is likely to result from SN2
reaction of iodide ion at the C1′ atom of initial com-
pound IIa. Factors responsible for higher stability of
the isomer with reversed configuration of substituents
on C1′ at high temperature were not clarified.
In order to estimate the effect of the size of the
substituent on the nitrogen atom on the possibility for
formation of 2-ethylidenedihydroindole, N-mesyl
derivative XIII was heated in boiling piperidine [11].
As a result, a mixture of 2-vinyldihydroindole XIV,
2-ethylidenedihydroindole XV, and 2-ethylindole XVI
was obtained (overall yield 90%). According to the
1H NMR data, the isomer ratio was ~1 : 1 : 1. The
reaction mixture was a viscous material which failed to
crystallize. Ethylidene derivative XV was likely to
undergo isomerization into 2-ethylindole XVI during
chromatography (the fraction of XVI considerably
increased). Compound XIV was isolated in 17% yield.
The remaining part of the product isolated by chroma-
tography was 2-ethylindole XVI (48%). Obviously,
2-ethylindole XVI can be formed only from ethylidene
derivative XV via 1,3-H shift from C3 to C1′. Fairly
high yield of indole XVI indicates that compound XIII
No appreciable dehydroiodination occurred when
compound IIa was heated in triethylamine or diiso-
propylamine over a period of 5 h, and the initial com-
pound was recovered almost completely. Despite
strong basicity of these amines, their boiling point is
likely to be insufficiently high to ensure dehydrohalo-
genation of IIa. Dehydrohalogenation of IIa with
a less basic amine (pyridine; pKa of the conjugate acid
is 5.2) also produced a small amount of N-tosyl deriv-
ative V, while the major product was quaternary salt
IX. The fraction of 2-vinyldihydroindole V did not
exceed 12%. The reduction of pyridinium salt IX with
sodium tetrahydridoborate gave compound X.
Reaction of compound IIa with amines
Yield, %
Reaction
Amine
conditions
V
–
VI VIII
Triethylamine
89°C, 5 h
84°C, 5 h
106°C, 5 h
–
–
–
–
Diisopropylamine
Piperidine
–
60
20
–
20
–
N-Methylpiperidine
N-Propylpiperidine
108°C, 30 h 80
152°C, 4 h 76
–
–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

REACTIONS OF N- AND C-ALKENYLANILINES: X.
1203
having a relatively small substituent on the nitrogen
atom preferentially undergoes Zaitsev elimination and
that compound IIa reacts according to Hofmann
(Scheme 4).
7.1 Hz) appears in a weaker field relative to the corre-
sponding signal of Ia (δ 2.78 ppm, d.q, J = 7.3, 8.2 Hz)
and Ic (δ 2.55 ppm, quint, J = 7.6 Hz) (Fig. 1).
Compound Ib does not fit the above relation; the
chemical shift of 3-H in Ib is similar to that of 3-H in
trans isomer IIb. Nevertheless, the coupling constants
As initial compound for the synthesis of 2-vinyl-
dihydroindole we used N-(2-nitrophenylsulfonyl)
derivative IIb. The product mixture obtained by heat-
ing compound IIb in boiling piperidine was subjected
to vacuum distillation. Two fractions were collected.
The first fraction (bp < 120°C) contained target prod-
uct XVIII in a mixture with XVII and XX. The second
fraction (bp 120–125°C) consisted mainly of com-
pound XVII with small impurities of XVIII and XX.
After chromatography, the overall yield of XVIII was
5%. The still residue was likely to contain mainly halo-
gen replacement product XIX. Presumably, isomeriza-
tion of initially formed ethylidene precursor XXI leads
to indole XX (Scheme 5).
of 2-H with 3-H in cis isomers Ia (δ 4.63 ppm, J2,1′
4.7, J2,3 = 8.2 Hz), Ib (δ 4.43 ppm, J2,1′ = 4.0, J2,3
=
=
8.1), and Ic (δ 4.68 ppm, J2,1′ = 4.4, J2,3 = 7.6 Hz) are
fairly large, indicating cis orientation of these protons
with respect to each other. On the other hand, small
coupling constants of 2-H in IIa (δ 3.41 ppm, J = 3.5,
7.2 Hz), IIb (δ 3.77 ppm, J = 2.5, 5.0 Hz), and IIc
(δ 3.70 ppm, J = 2.2, 8.2 Hz) with 3-H (J2,3 = 3.5, 2.5,
and 2.2 Hz, respectively) are typical of their trans
arrangement. The 1′-H proton in the ethyl fragment of
cis isomers Ia (δ 4.39 ppm, J1′,2 = 4.7, J1′,Me = 7.1 Hz),
Ib (δ 4.62 ppm, J = 4.0, 7.2 Hz), and Ic (δ 4.28 ppm
(J = 4.4, 6.9 Hz) resonates as a doublet of quartets. The
corresponding signal of trans isomer IIa is a quintet
(δ 4.47 ppm, J = 7.2 Hz), while the 1′-H signals of IIc
(δ 4.09 ppm, J = 7.1, 8.2 Hz) (Fig. 2) and IIb
(δ 4.49 ppm, J = 5.0, 7.2 Hz) are doublets of quartets.
The structure of the synthesized compounds was
determined on the basis of their elemental composi-
tions and spectral data. Mutual orientation of substit-
uents at C2 and C3 in compounds Ia–Ic and IIa–IIc
was assigned taking into account published data [12].
1
The 3-H signal in the H NMR spectra of IIa
Protons in the methyl group on C3 in cis isomers
Ia–Ic give rise to a doublet at δ 1.30–1.45 ppm, and
methyl protons in the iodoethyl fragment resonate at δ
(δ 3.05 ppm, d.q, J = 3.5, 7.0 Hz), IIb (δ 3.15 ppm,
d.q, J = 2.5, 7.0 Hz), and IIc (δ 2.85 ppm, d.q, J = 2.2,
Scheme 4.
Me
Me
Me
Me
Piperidine
reflux
Me
Me
Me
XVI
+
Me
CH2
H
Me
I
Me
Me
+
+
N
N
N
N
H
Ms
Ms
Ms
Ms
XIII
XIV
XV
XV
XVI
~1,3-H
Scheme 5.
Me
Me
Me
NO2
Piperidine
reflux
Me
Me
Me
CH2
H
Me
H
N
+
N
I
Me
N
N
N
H
H
H
H
SO2C6H4NO2-2
IIb
XVIII
XVII, 92%
XIX
Me
Me
Me
Me
Me
Me
+
+
N
H
N
H
XXI
XX, 2%
~1,3-H
XXI
XX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

MAZGAROVA et al.
1204
Me
3
Me
2
1'
N
I
Ts
Me
2-H
1′-H
3-H
2.5
5.0
4.5
4.0
δ, ppm
Fig. 1. A fragment of the 1H NMR spectrum of compound Ic corresponding to resonances of the 1′-H, 2-H, and 3-H protons.
1.55–1.80 ppm. The difference in the chemical shifts
of these methyl protons reaches 0.5 ppm. In going
from cis orientation of the 3-Me group and 1-iodoethyl
group on C2 to trans (IIa–IIc) the difference in the
chemical shifts of the methyl protons increased to
1.50 ppm. The CH3CHI signal of IIa (δ 0.60 ppm,
J = 7.0 Hz), IIb (δ 0.85 ppm, J = 7.2 Hz), and IIc
(δ 0.50 ppm, J = 7.1 Hz) appeared in a stronger field,
while the 3-Me signal of IIa (δ 2.00 ppm, J = 7.2 Hz),
IIb (δ 1.98 ppm, J = 7.0 Hz), and IIc (δ 2.05 ppm, J =
7.1 Hz) was displaced downfield.
Comparison of the 1H NMR spectra of IIa and XIII
showed that the chemical shift of 3-H depends to some
extent on the substituent on the nitrogen atom. The 3-H
signal of IIa was located in a stronger field (δΔ ≈
0.3 ppm) relative to the 3-H signal of XIII [11]. Com-
pounds IIa and XIII are characterized by different
multiplicities of the 1′-H signal; the latter appears as
a quintet at δ 4.47 ppm (J2,1′ = 7.2 Hz) in the 1H NMR
spectrum of IIa but as a doublet of quartets in the
spectrum of N-mesyl analog XIII [11].
The vinyl group in dihydroindoles V and XIV gives
rise to characteristic signals from protons in the termi-
nal methylene group with a small geminal coupling
constant (J = 1.0 Hz); the vicinal coupling constants
with 1′-H are Jcis = 10.2–10.3 and Jtrans = 16.9–
17.6 Hz. Ethylidene derivative VI was identified in
a mixture with compound V by the presence of
a quartet signal from 1′-H at δ ~6 ppm.
The mass spectrum of XI (positive ion detection)
contained the molecular ion peak with m/z 374
[M + H]+. The negative ion mass spectrum was less
informative. The most abundant ion therein was tol-
uenesulfonyl fragment, m/z 155 [CH3C6H4SO2]–.
Ester XI displayed fairly characteristic signals from
the formate group in the 1H and 13C NMR spectra. The
OCHO signal appeared in the 1H NMR spectrum of XI
as a singlet at δ 7.80 ppm, and the carbonyl carbon
atom gave rise to a doublet at δC 159.5 ppm in the
JMOD 13C NMR spectrum.
Comparison of the NMR spectra of compound XII
(the assumed product of inversion of configuration at
C1′) and isomers Ia and IIa showed that the CHICH3
signal of XII (δ 0.50 ppm), as well as of IIa, is located
in a stronger field than the corresponding signal of
stereoisomer Ia (Δδ ~0.85 ppm). The positions of other
signals in the 1H NMR spectra of these compounds are
also considerably different. Isomerization with forma-
tion of 3-iodo-1,2,3,4-tetrahydroquinoline derivative
was ruled out on the basis of the calculation data,
according to which the chemical shift of C2 neighbor-
ing to the nitrogen atom in dihydroindole derivatives is
about δC 75 ppm, whereas C2 in quinoline derivatives
resonates at δC ~60 ppm. In addition, the methyl
carbon signal of the iodoethyl group in the 13C NMR
Me
3
Me
2
1'
N
I
Ts
Me
2-H
1′-H
3-H
4.0
3.5
3.0
δ, ppm
1
Fig. 2. A fragment of the H NMR spectrum of compound
IIc corresponding to resonances of the 1′-H, 2-H, and 3-H
protons.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

REACTIONS OF N- AND C-ALKENYLANILINES: X.
1205
Scheme 6.
Me
Me
Me
(1) LiAlH4
(2) H2O, 15% NaOH
CH2=CHCH2Br
K2CO3, CH2Cl2
Me
Me
Me
CH2
CH2
CH2
N
N
H
N
CH2
Ts
V
XVIII, 50%
XXII, 80%
spectrum of XII was displaced appreciably downfield
(δC 30.6 ppm) due to the presence of heavy iodine
atom at the neighboring carbon atom (cf. δC 34.1 ppm
for isomer IIa).
ene chloride, 200 ml of water was added, the mixture
was stirred for 5 min, and the organic phase was
treated with a 10% solution of Na2S2O3 (3×100 ml)
and water (200 ml), dried over Na2SO4, and evaporated
under reduced pressure. The residue was treated with
100 ml of ethanol, the mixture was stirred, and the
precipitate was filtered off and recrystallized from
ethanol (200 ml). Yield 2.86 g (42%), mp 169°C (from
1
The H NMR spectrum of compound XVIII ob-
tained from dihydroindole derivatives IIb and V
retained signal splitting pattern characteristic of the
terminal methylene group.
1
EtOH). H NMR spectrum (CDCl3), δ, ppm: 0.60 d
The reduction of tosyl derivative V with excess
lithium tetrahydridoaluminate afforded 50% of XVIII,
i.e., the yield was slightly higher than in the reaction of
nitrobenzenesulfonyl derivative IIb with piperidine.
The subsequent treatment of the reaction mixture with
water to neutralize large excess of the reducing agent
is a fairly long and unsafe process, for the reaction is
rather vigorous. The alkylation of XVIII with allyl
bromide gave N-allyl derivative XXII (Scheme 6).
(3H, CH3, J = 7.0 Hz), 2.00 d (3H, CH3, J = 7.2 Hz),
2.31 s (3H, CH3), 2.37 s (3H, CH3), 3.05 d.q (1H, 3-H,
J = 3.5, 7.0 Hz), 3.41 d.d (1H, 2-H, J = 3.5, 7.2 Hz),
4.47 quint (1H, 1′-H, J = 7.2 Hz), 6.82 s (1H, 4-H),
7.04 d (1H, Harom, J = 8.0 Hz), 7.17 d (2H, Harom, J =
8.3 Hz), 7.50 d (2H, Harom, J = 8.3 Hz), 7.57 d (1H,
H
arom, J = 8.0 Hz). 13C NMR spectrum (CDCl3), δC,
ppm: 21.5, 21.8, 22.5, 34.1 (CH3); 25.4 (C1′), 43.1
(C3), 75.4 (C2); 117.6, 125.0, 127.9, 129.0, 129.4 (C4,
C6, C7, C2′, C6′, C3′, C5′); 134.3, 135.5, 136.9, 139.0,
143.4 (C3a, C5, C7a, C1′, C4′). Found, %: C 50.01;
H 4.81; I 27.78; N 2.98; S 6.95. C19H22INO2S. Calcu-
lated, %: C 50.12; H 4.87; I 27.87; N 3.08; S 7.04.
EXPERIMENTAL
The IR spectra were recorded on a UR-20 spec-
trometer. The 1H and 13C NMR spectra were measured
on a Bruker AM-300 spectrometer at 300.13 and
75.47 MHz, respectively, using tetramethylsilane as
internal reference. The mass spectrum (atmospheric
pressure chemical ionization) was obtained on
a Shimadzu 2010EV LC–MS instrument using meth-
anol–water (1:1) as eluent. The elemental composi-
tions were determined on a Hewlett–Packard M-185B
CHN analyzer. Silica gel LS (40–100 μm, Lancaster)
was used for column chromatography. Qualitative
TLC analyses were performed using Sorbfil plates
(Sorbpolimer close corporation, Krasnodar, Russia);
spots were developed by treatment with iodine vapor.
The first alcoholic mother liquor was evaporated
under reduced pressure at a bath temperature of no
higher than 40°C, the dry residue was dissolved in
a minimal amount of benzene (~10 ml), and the solu-
tion was applied to a column charged with silica gel
(60 g). Elution with benzene gave (2R*,3S*)-2-[(1S*)-
1-iodoethyl]-3,5-dimethyl-1-(4-methylphenylsul-
fonyl)-2,3-dihydro-1H-indole (Ia) containing an un-
1
identified impurity. Rf 0.6 (C6H6). H NMR spectrum
(CDCl3), δ, ppm: 1.35 d (3H, CH3, J = 7.3 Hz), 1.80 d
(3H, CH3, J = 7.1 Hz), 2.28 s (3H, CH3), 2.36 s (3H,
CH3), 2.78 d.q (1H, 3-H, J = 7.3, 8.2 Hz), 4.39 d.q
(1H, 1′-H, J = 4.7, 7.1 Hz), 4.63 d.d (1H, 2-H, J = 4.7,
8.2 Hz), 6.76 s (1H, 4-H), 7.09 d (1H, Harom, J =
8.0 Hz), 7.17 d (2H, Harom, J = 8.0 Hz), 7.53 d (2H,
Harom, J = 8.0 Hz), 7.58 d (1H, Harom, J = 8.0 Hz).
(2R*,3R*)-2-[(1S*)-1-Iodoethyl]-3,5-dimethyl-
1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-indole
(IIa). A mixture of 4.93 g (15 mmol) of p-toluene-
sulfonamide (IIIa), 8.10 g (96 mmol) of sodium
hydrogen carbonate, and 7.62 g (30 mmol) of iodine in
200 ml of methylene chloride was stirred for ~24 h at
20°C, the progress of the reaction being monitored by
TLC (eluent CH2Cl2). When the reaction was com-
plete, the mixture was diluted with 500 ml of methyl-
(2R*,3R*)-2-[(1S*)-1-Iodoethyl]-3,5-dimethyl-
1-(2-nitrophenylsulfonyl)-2,3-dihydro-1H-indole
(IIb). A mixture of 9.3 g (26 mmol) of 2-nitroben-
zenesulfonamide (IIIb), 15.6 g (185 mmol) of sodium
hydrogen carbonate, and 14.1 g (55 mmol) of iodine in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

MAZGAROVA et al.
arom, J = 8.2 Hz). Found, %: C 49.96; H 4.80; I 27.79;
1206
300 ml of methylene chloride was stirred for ~104 h at
20°C. The mixture was diluted with 500 ml of methy-
lene chloride and filtered, and the precipitate was
washed with 100 ml of methylene chloride. The organ-
ic phase was treated with a 10% solution of Na2S2O3
(3×200 ml) and water (200 ml), dried over Na2SO4,
and evaporated under reduced pressure. The residue
was stirred with 100 ml of ethanol, the mixture was
stirred, and the precipitate was filtered off and recrys-
tallized from ethanol (200 ml). However, we failed to
isolate pure compound IIb by repeated crystallization
from ethanol. It was isolated by column chromatog-
raphy on silica gel using benzene as eluent. Yield 2.8 g
H
N 3.04; S 6.97. C19H22INO2S. Calculated, %: C 50.12;
H 4.87; I 27.87; N 3.08; S 7.04.
4-Methyl-N-{4-methyl-2-[(2E)-1-methylbut-2-en-
1-yl]phenyl}benzenesulfonamide (IIIa). 2-(1-Meth-
ylbut-2-en-1-yl)-4-methylaniline (IVa), 3.5 g
(20 mmol), was dissolved in 20 ml of benzene, 4 ml of
triethylamine and 4.18 g (22 mmol) of p-toluenesul-
fonyl chloride were added, and the mixture was left to
stand for 24 h at 20°C. The mixture was treated with
10 ml of water, stirred for 30 min, and extracted with
60 ml of methylene chloride. The organic phase was
washed with 10 ml of water, dried over MgSO4, and
evaporated under reduced pressure to isolate com-
pound IIIa as a viscous oily substance.
1
(20%), mp 171–172°C (from EtOH). H NMR spec-
trum (CDCl3), δ, ppm: 0.85 d (3H, CH3, J = 7.2 Hz),
1.98 d (3H, CH3, J = 7.0 Hz), 2.35 s (3H, CH3),
3.15 d.q (1H, 3-H, J = 2.5, 7.0 Hz), 3.77 d.d (1H, 2-H,
J = 2.5, 5.0 Hz), 4.49 d.q (1H, 1′-H, J = 5.0, 7.2 Hz),
6.91 s (1H, 4-H), 7.09 d.d (1H, Harom, J = 1.0, 8.2 Hz),
7.44–7.68 m (5H, Harom). Found, %: C 44.41; H 3.90;
I 25.93; N 5.61; S 6.37. C18H19IN2O4S. Calculated, %:
C 44.46; H 3.94; I 26.09; N 5.76; S 6.59.
Compounds IIIb and IIIc were synthesized in
a similar way.
N-{4-Methyl-2-[(2E)-1-methylbut-2-en-1-yl]-
phenyl}-2-nitrobenzenesulfonamide (IIIb) was syn-
thesized from 17.5 g (100 mmol) of pentenylaniline
IVb and 26.6 g (120 mmol) of 2-nitrobenzenesulfonyl
chloride. The product was isolated as a viscous mate-
rial. Attempted crystallization from ethanol gave com-
pound IIIb as an oily substance which was brought
into iodocyclization.
A mixture of stereoisomers Ic and IIc was obtained
as described above for Ia/IIa from 0.49 g (1.5 mmol)
of p-toluenesulfonamide (IIIc). After appropriate treat-
ment of the reaction mixture and removal of the sol-
vent under reduced pressure, the residue was subjected
to column chromatography on silica gel using benzene
as eluent.
4-Methyl-N-{2-methyl-6-[(2E)-1-methylbut-2-en-
1-yl]phenyl}benzenesulfonamide (IIIc) was syn-
thesized in a similar way from 1.75 g (10 mmol) of
alkenylaniline IVc and 2.09 g (11 mmol) of p-toluene-
sulfonyl chloride. Viscous material crystallized upon
addition of methanol. Yield 2.63 g (80%), mp 115°C
(from EtOH). If that material was dissolved in hot
ethanol, compound IIIc did not crystallize on cooling.
Found, %: C 69.21; H 7.02; N 4.22; S 9.69.
C19H23NO2S. Calculated, %: C 69.27; H 7.04; N 4.25;
S 9.73.
(2R*,3S*)-2-[(1S*)-1-Iodoethyl]-3,7-dimethyl-
1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-indole
(Ic). Yield 0.24 g (35%). H NMR spectrum (CDCl3),
1
δ, ppm: 1.30 d (3H, CH3, J = 7.6 Hz), 1.55 d (3H, CH3,
J = 6.9 Hz), 2.35 s (3H, CH3), 2.62 s (3H, CH3),
2.55 quint (1H, 3-H, J = 7.6 Hz), 4.28 d.q (1H, 1′-H,
J = 4.4, 6.9 Hz), 4.68 d.d (1H, 2-H, J = 4.4, 7.6 Hz),
6.77 d (1H, Harom, J = 6.6 Hz), 7.05–7.17 m (4H,
Harom), 7.45 d (2H, Harom, J = 8.2 Hz). Found, %:
C 49. 99; H 4. 81; I 27. 82; N 3. 03; S 6. 98.
C19H22INO2S. Calculated, %: C 50.12; H 4.87; I 27.87;
N 3.08; S 7.04.
(2S*,3R*)-3,5-Dimethyl-1-(4-methylphenylsul-
fonyl)-2-vinyl-2,3-dihydro-1H-indole (V). A mixture
of 0.455 g (1 mmol) of compound IIa and 6 ml of
N-methylpiperidine or N-propylpiperidine was heated
under reflux for 30 or 4 h, respectively. The solvent
was removed under reduced pressure, the residue was
dissolved in 50 ml of carbon tetrachloride, and the
solution was treated with 30 ml of water by shaking in
a separatory funnel. The organic phase was washed
with 20 ml of 3% aqueous HCl and 20 ml of water,
dried over MgSO4, and evaporated under reduced
pressure. The residue was dissolved in 5 ml of boiling
ethanol; after cooling, the precipitate was filtered off.
Yield 0.26 g (80%) (in N-methylpiperidine), 0.25 g
(2R*,3R*)-2-[(1S*)-1-Iodoethyl]-3,7-dimethyl-
1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-indole
(IIc) was isolated by further elution. Yield 0.21 g
1
(31%). H NMR spectrum (CDCl3), δ, ppm: 0.50 d
(3H, CH3, J = 7.1 Hz), 2.05 d (3H, CH3, J = 7.1 Hz),
2.35 s (3H, CH3), 2.62 s (3H, CH3), 2.85 d.q (1H, 3-H,
J = 2.2, 7.1 Hz), 3.70 d.d (1H, 2-H, J = 2.2, 8.2 Hz),
4.09 d.q (1H, 1′-H, J = 7.1, 8.2 Hz), 6.88 d (1H, Harom
,
J = 6.8 Hz), 7.03–7.20 m (4H, Harom), 7.36 d (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

REACTIONS OF N- AND C-ALKENYLANILINES: X.
1207
(76%) (in N-propylpiperidine); mp 141–142°C (from
EtOH). H NMR spectrum (CDCl3), δ, ppm: 0.70 d
and gaseous HCl was bubbled through the solution.
After a few minutes, the solution turned turbid, but
then rapidly clarified. Bubbling of HCl was continued
for 10 min more, and viscous hydrochloride VIII
deposited on the walls of the reaction test tube. The
organic phase was removed by decanting, and hydro-
chloride VIII remaining on the walls was dried under
1
(3H, CH3, J = 7.0 Hz), 2.25 s (3H, CH3), 2.40 s (3H,
CH3), 2.85 d.q (1H, 3-H, J = 4.3, 7.0 Hz), 4.07 d.d.t
(1H, 2-H, J = 1.0, 4.3, 6.7 Hz), 5.15 d.t (2′-H, J = 1.0,
10.3 Hz), 5.38 d.t (1H, 2′-H, J = 1.0, 16.9 Hz),
5.95 d.d.d (1H, 1′-H, J = 6.7, 10.3, 16.9 Hz), 6.80 s
(1H, 4-H), 7.02 d (1H, Harom, J = 7.4 Hz), 7.22 d (2H,
1
reduced pressure. Yield 0.1 g (89%). H NMR spec-
trum (CDCl3), δ, ppm: 0.60 br.s (3H, CH3), 1.30–
1.60 m (6H, CH2), 1.30 s (3H, CH3), 2.25 s (3H, CH3),
2.40 s (3H, CH3), 3.00 m (1H, 3-H), 3.10 m (1H, 2-H),
3.40–3.70 m (4H, CH2), 3.80 m (1H, 1′-H), 6.88 s
(4-H), 7.04 d (1H, Harom, J = 8.3 Hz), 7.22 d (2H,
H
arom, J = 8.0 Hz), 7.51 d (1H, Harom, J = 7.4 Hz),
7.60 d (2H, Harom, J = 8.0 Hz). Found, %: C 69.47;
H 6.25; N 4.04; S 9.58. C19H21NO2S. Calculated, %:
C 69.69; H 6.46; N 4.28; S 9.79.
(2R*,3R*)-3,5-Dimethyl-1-(4-methylphenylsul-
fonyl)-2-[(1R*)-1-(piperidin-1-yl)ethyl]-2,3-dihydro-
1H-indole (VII). A solution of 1.9 g (4.17 mmol) of
compound IIa in 20 ml of piperidine was heated for
4 h under reflux. Piperidine was removed under re-
duced pressure, the residue was dissolved in 200 ml of
methylene chloride, the solution was washed with
water (3×30 ml), treated with 5% aqueous HCl
(30 ml) under shaking, washed with water (30 ml), and
dried over MgSO4. The solvent was removed under
reduced pressure (water-jet pump), and the residue was
crystallized from ethanol (10 ml). Crystals of 2-vinyl
and 2-ethylidene derivatives V and VI were filtered
off. Yield 0.92 g (68%), ratio V:VI = 3:1.
H
arom, J = 8.2 Hz), 7.53 d (1H, Harom, J = 8.3 Hz),
7.59 d (2H, Harom, J = 8.2 Hz), 12.2 br.s (HCl). Found,
%: C 63.98; H 7.29; Cl 7.87; N 6.05; S 6.96.
C24H33ClN2O2S. Calculated, %: C 64.19; H 7.41;
Cl 7.90; N 6.24; S 7.14.
1-[(1R*)-1-{(2R*,3R*)-3,5-Dimethyl-1-(4-methyl-
phenylsulfonyl)-2,3-dihydro-1H-indol-2-yl}ethyl]-
pyridinium iodide (IX). A mixture of 0.6 g
(1.32 mmol) of compound IIa and 40 ml of pyridine
was heated for 24 h under reflux. Excess pyridine was
removed under reduced pressure, the solid residue was
treated with 10 ml of water, and the mixture was
thoroughly stirred and extracted with chloroform. The
organic phase was washed with water (2×80 ml), dried
over MgSO4, filtered from the drying agent, and
evaporated under reduced pressure. The residue was
treated with 20 ml of carbon tetrachloride, the mixture
was thoroughly stirred on heating under reflux for
a few minutes, and the undissolved brown quaternary
salt was filtered off. Yield 0.5 g (71%), mp 294–
The mother liquor was evaporated under reduced
pressure, the residue was dissolved in 100 ml of
methylene chloride, and the solution was washed with
a saturated solution of sodium hydrogen carbonate
until carbon dioxide no longer evolved and dried over
MgSO4. The solvent was removed under reduced pres-
sure, and the residue was dissolved in boiling ethanol.
After cooling, the powder-like precipitate (0.27 g) was
filtered off; it was compound VII containing ~3% of V
and ~1% of VI as impurities. Compound VII was
purified by repeated recrystallization from ethanol,
1
295°C. H NMR spectrum (CDCl3), δ, ppm: 0.46 d
(3H, CH3, J = 7.2 Hz), 2.09 d (3H, CH3, J = 6.8 Hz),
2.19 s (3H, CH3), 2.26 s (3H, CH3), 3.12 d.q (1H, 3-H,
J = 1.0 6.8 Hz), 4.29 d.d (1H, 2-H, J = 1.0, 7.2 Hz),
4.93 quint (1H, 1′-H, J = 7.2 Hz), 6.75 s (1H, 4-H),
6.98 d (1H, Harom, J = 7.8 Hz), 7.11 d (2H, Harom, J =
8.3 Hz), 7.43 d (1H, Harom, J = 7.8 Hz), 7.46 d (2H,
1
mp 169–170°C (from EtOH). H NMR spectrum
(CDCl3), δ, ppm: 0.48 d (3H, CH3, J = 7.0 Hz), 0.80 d
(3H, CH3, J = 6.8 Hz), 1.30–1.60 m (6H, CH2), 2.20 s
(3H, CH3), 2.30 s (3H, CH3), 2.49–2.60 m (4H, CH2),
2.85 d.q (1H, 1′-H, J = 3.0, 7.0 Hz), 3.00 d.q (1H, 3-H,
J = 2.0, 6.8 Hz), 3.84 m (1H, 2-H), 6.69 s (4-H), 6.90 d
(1H, Harom, J = 8.0 Hz), 7.12 d (2H, Harom, J = 8.0 Hz),
H
arom, J = 8.3 Hz), 7.97 d.d (2H, Harom, J = 5.8,
7.7 Hz), 8.37 t (1H, Harom, J = 7.7 Hz), 9.22 d (2H,
arom, J = 5.8 Hz). Found, %: C 53.76; H 4.87; I 23.43;
H
N 5.02; S 5.81. C24H27IN2O2S. Calculated, %: C 53.94;
H 5.09; I 23.74; N 5.24; S 6.00.
7.48 d (1H, Harom, J = 8.0 Hz), 7.52 d (2H, Harom
,
The residue obtained after evaporation of CCl4 was
recrystallized from ethanol to isolate 0.12 g of a mix-
ture of approximately equal amounts of V and IX.
J = 8.0 Hz).
(2R*,3R*)-3,5-Dimethyl-1-(4-methylphenylsul-
fonyl)-2-[(1R*)-1-(piperidin-1-yl)ethyl]-2,3-dihydro-
1H-indole hydrochloride (VIII). Compound VII,
0.11 g (0.25 mmol), containing a small impurity of V
and VI was dissolved in 10 ml of carbon tetrachloride,
(2R*,3R*)-2-{(1R*)-1-[3,6-Dihydropyridin-
1(2H)-yl]ethyl}-3,5-dimethyl-1-(4-methylphenylsul-
fonyl)-2,3-dihydro-1H-indole (X) was synthesized by
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

MAZGAROVA et al.
1208
reduction of 0.422 g (0.79 mmol) of IX with 0.121 g
(3.16 mmol) of sodium tetrahydridoborate in 5 ml of
anhydrous ethanol. When the reaction was complete,
the mixture was diluted with water and extracted with
30 ml of methylene chloride. The extract was washed
with 10 ml of water, dried over MgSO4, and evaporat-
ed, and the residue was crystallized from ethanol,
6.9 Hz), 3.70 d.d (1H, 2-H, J = 2.5, 3.8 Hz), 4.55 d.q
(1H, 1′-H, J = 3.8, 6.9 Hz), 6.60 s (1H, 4-H), 6.85 d
(1H, Harom, J = 8.0 Hz), 6.99 d (2H, Harom, J = 8.2 Hz),
7.41 d (2H, Harom, J = 8.2 Hz), 7.44 d (1H, Harom, J =
8.0 Hz). 13C NMR spectrum (CDCl3), δC, ppm: 20.1,
21.4, 21.8, 30.6 (CH3); 24.4 (C1′), 38.4 (C3), 74.3 (C2);
116.2, 124.8, 127.6, 129.1, 129.4 (C4, C6, C7, C2′, C6′,
C3′, C5′); 134.2, 135.1, 136.6, 139.9, 143.5 (C3a, C5,
C7a, C1′, C4). Found, %: C 50.03; H 4.78; I 27.75;
N 3.04; S 6.97. C19H22INO2S. Calculated, %: C 50.12;
H 4.87; I 27.87; N 3.08; S 7.04.
1
mp 153–154°C. H NMR spectrum (CDCl3), δ, ppm:
0.51 d (3H, CH3, J = 7.1 Hz), 0.91 d (3H, CH3, J =
6.8 Hz), 2.07–2.11 m (2H, CH2), 2.26 s (3H, CH3),
2.34 s (3H, CH3), 2.61–2.85 m (2H, CH2), 2.91–3.20 m
(4H, CH2, 3-H, 1′-H), 3.97 d.d (1H, 2-H, J = 2.6,
3.5 Hz), 5.62–5.78 m (2H, CH=CH), 6.76 s (1H, 4-H),
6.98 d (1H, Harom, J = 8.0 Hz), 7.17 d (2H, Harom, J =
8.0 Hz), 7.55 d (1H, Harom, J = 8.0 Hz), 7.58 d (2H,
Harom, J = 8.0 Hz). Found, %: C 70.14; H 7.31; N 6.77;
S 7.74. C24H30N2O2S. Calculated, %: C 70.21; H 7.36;
N 6.82; S 7.81.
(2S*,3R*)-3,5-Dimethyl-1-methylsulfonyl-
2-vinyl-2,3-dihydro-1H-indole (XIV). A mixture of
1.9 g (5.01 mmol) of compound XIII and 20 ml of
piperidine was heated for 5 h under reflux. The solvent
was removed under reduced pressure, the residue was
dissolved in 50 ml of methylene chloride, the solution
was treated with 30 ml of water, and the mixture was
shaken in a separatory funnel. The organic phase was
separated, washed with 3% aqueous HCl (20 ml) on
shaking and water (20 ml), and dried over MgSO4. The
solvent was removed under reduced pressure, and the
residue was subjected to column chromatography on
silica gel using benzene as eluent to isolate (in order of
elution) 0.6 g (48%) of indole XVI and 0.217 g (17%)
of 2-vinyl derivative XIV as a viscous material, Rf 0.2
(benzene). 1H NMR spectrum (CDCl3), δ, ppm: 1.35 d
(3H, CH3, J = 7.0 Hz), 2.30 s (3H, CH3), 2.90 s (3H,
CH3), 3.05 d.q (1H, 3-H, J = 4.4, 7.0 Hz), 4.27 d.d.d
(1H, 2-H, J = 1.0, 4.4, 7.3 Hz), 5.17 d.t (2′-H, J =
1.0, 10.2 Hz), 5.38 d.t (1H, 2′-H, J = 1.0, 17.6 Hz),
5.95 d.d.d (1H, 1′-H, J = 7.3, 10.2, 17.6 Hz), 6.95 s
(1H, 4-H), 7.02 d (1H, Harom, J = 9.0 Hz), 7.30 d (1H,
Harom, J = 9.0 Hz). Found, %: C 61.97; H 6.55; N 5.34;
S 12.51. C13H17NO2S. Calculated, %: C 62.12; H 6.82;
N 5.57; S 12.76.
(1R*)-1-{(2R*,3R*)-3,5-Dimethyl-1-(4-methyl-
phenylsulfonyl)-2,3-dihydro-1H-indol-2-yl}ethyl
formate (XI). A solution of 0.455 g (1 mmol) of
compound IIa in 5 ml of DMF was heated for 2 h
under reflux. The solvent was removed under reduced
pressure, 50 ml of methylene chloride and 30 ml of
water were added to the residue, the mixture was
shaken in a separatory funnel, and the organic layer
was separated, washed with water (20 ml), and dried
over Na2SO4. The solvent was removed under reduced
pressure, and the residue was subjected to column
chromatography using benzene as eluent. Yield 0.16 g
1
(43%). Colorless powder, mp 145°C. H NMR spec-
trum (CDCl3), δ, ppm: 0.45 d (3H, CH3, J = 7.1 Hz),
1.08 d (3H, CH3, J = 6.5 Hz), 2.15 s (3H, CH3), 2.20 s
(3H, CH3), 2.85 d.q (1H, 3-H, J = 2.6, 6.5 Hz),
3.70 d.d (1H, 2-H, J = 2.6, 4.4 Hz), 5.25 m (1H, 1′-H),
6.60 s (1H, 4-H), 6.89 d (1H, Harom, J = 8.0 Hz), 7.00 d
(2H, Harom, J = 8.0 Hz), 7.45 d (2H, Harom, J = 8.0 Hz),
7.50 d (1H, Harom, J = 8.0 Hz), 7.80 s (1H, OCHO).
13C NMR spectrum (CDCl3), δC, ppm: 14.1, 21.1, 21.5,
22.6 (CH3); 36.8 (C3), 70.1 (C2), 72.0 (C1′); 116.7,
124.5, 127.4, 128.8, 129.4 (C4, C6, C7, C2′, C6′, C3′,
C5′); 134.2, 134.4, 137.1, 139.1, 143.6 (C3a, C5, C7a,
C1′, C4); 159.5 (OCHO). Mass spectrum, m/z: 374
[M + H]+, 155 [CH3C6H4SO2]–. Found, %: C 64.09;
H 6.03; N 3.59; S 8.31. C20H23NO4S. Calculated, %:
C 64.32; H 6.21; N 3.75; S 8.58.
2-Ethyl-3,5-dimethyl-1-methylsulfonyl-1H-in-
dole (XVI). Yield 0.6 g (48%), viscous transparent
material, Rf 0.5 (benzene). 1H NMR spectrum (CDCl3),
δ, ppm: 1.28 t (3H, CH3, J = 7.4 Hz), 2.20 s (3H, CH3),
2.40 s (3H, CH3), 2.85 s (3H, CH3), 2.95 q (2H, 1′-H,
J = 7.4 Hz), 7.12 d (1H, Harom, J = 1.3, 8.4 Hz), 7.27 s
(1H, 4-H), 7.89 d (1H, Harom, J = 8.4 Hz). Found, %:
C 61.94; H 6.57; N 5.30; S 12.48. C13H17NO2S. Cal-
culated, %: C 62.12; H 6.82; N 5.57; S 12.76.
Further elution gave (2R*,3R*,1′R*)-isomer XII.
Yield 0.09 g (20%), colorless powder, mp 177°C.
1H NMR spectrum (CDCl3), δ, ppm: 0.50 d (3H, CH3,
J = 6.9 Hz), 1.43 d (3H, CH3, J = 6.9 Hz), 2.15 s (3H,
CH3), 2.20 s (3H, CH3), 2.93 d.q (1H, 3-H, J = 2.5,
1-(2-Nitrophenyl)piperidine (XVII). Yield 9.56 g
(92%), bp 125–128°C (2 mm). 13C NMR spectrum
(CDCl3), δC, ppm: 23.8 (C4), 25.8 (C3, C5), 52.8 (C2,
C6); 120.4, 120.7, 125.8, 133.2 (Carom), 133.3 (C1′),
146.9 (C2′). Mass spectrum: m/z 207 [M + H]+.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

REACTIONS OF N- AND C-ALKENYLANILINES: X.
1209
(2S*,3R*)-3,5-Dimethyl-2-vinyl-2,3-dihydro-1H-
indole (XVIII). a. A solution of 0.27 g (0.6 mmol) of
compound V in 20 ml of THF was added to a cold
suspension of 0.456 g (12 mmol) of LiAlH4 in 40 ml of
THF. The mixture was stirred for 48 h at room tem-
perature and cooled to 0°C, and 1.2 ml of water was
added dropwise. Vigorous evolution of hydrogen was
observed after addition of every drop of water. A 15%
solution of sodium hydroxide, 1.2 ml, and water,
3.6 ml, were then added. The resulting suspension con-
sisting of small granules was filtered, the solid material
was washed with THF on a filter, the filtrate and the
washings were evaporated, and the residue was sub-
jected to column chromatography using benzene as
eluent. Yield 0.05 g (50%).
benzene, 3:2). When initial compound XVIII disap-
peared, the mixture was diluted with 35 ml of methy-
lene chloride and treated with 10 ml of water under
stirring. The organic phase was separated and dried
over K2CO3. The solvent was removed, and the residue
was passed through a short column using benzene as
eluent. Yield 0.136 g (80%), transparent liquid which
turned dark on exposure to air, Rf 0.7 (C6H6). 1H NMR
spectrum (CDCl3), δ, ppm: 1.25 d (3H, CH3, J =
6.7 Hz), 2.20 s (3H, CH3), 2.95 d.q (1H, 3-H, J = 5.9,
6.7 Hz), 3.40–3.60 m (2H, CH2), 3.80 d.d (1H, 2-H,
J = 5.9, 7.5 Hz), 5.10–5.30 m and 5.75–5.90 m (6H,
CH=CH2), 6.40 d (1H, 7-H, J = 7.8 Hz), 6.79 s (1H,
4-H), 6.83 d (1H, 6-H, J = 7.8 Hz). Found, %: C 84.34;
H 8.89; N 6.49. C15H19N. Calculated, %: C 84.46;
H 8.98; N 6.57.
b. A solution of 24.3 g (50 mmol) of compound IIb
in 160 ml of piperidine was heated for 6 h under
reflux. The solvent was removed under reduced pres-
sure, the residue was dissolved in 250 ml of methylene
chloride, the solution was treated in a separatory
funnel with a saturated solution of sodium hydrogen
carbonate until carbon dioxide no longer evolved, and
the organic phase was separated, washed with water
(70 ml), and dried over MgSO4. The solvent was
removed under reduced pressure (water-jet pump), and
the residue was subjected to fractional distillation in
a vacuum (oil pump). A fraction with bp 112–120°C
(2 mm) was collected; it was a mixture of approxi-
mately equal amounts of compounds XVIII and XX
and a small amount of 1-(2-nitrophenyl)piperidine
(XVII). By column chromatography using benzene as
eluent we isolated (from first fractions) 0.35 g (2%) of
XVIII as a brown liquid. IR spectrum: ν 3385 cm–1
(NH). 1H NMR spectrum (CDCl3), δ, ppm: 1.30 d (3H,
CH3, J = 7.5 Hz), 2.25 s (3H, CH3), 2.95 d.q (1H, 3-H,
J = 6.7, 7.5 Hz), 3.80 d.d (1H, 2-H, J = 6.7, 7.5 Hz),
6.00 d.d.d (1H, 1′-H, J = 7.5, 10,2, 17.1 Hz), 5.10 d.d
(1H, 2′-H, J = 0.9, 10.2 Hz), 5.25 d.d (2′-H, J = 0.9,
17.1 Hz), 6.55 d (1H, 7-H, J = 7.7 Hz), 6.82 d (1H,
6-H, J = 7.7 Hz), 6.90 s (1H, 4-H). Found, %: C 83.04;
H 8.67; N 7.99. C12H15N. Calculated, %: C 83.19;
H 8.73; N 8.08.
This study was performed under financial support
by the Academy of Sciences of Bashkortostan
Republic.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012