Approach to preparative synthesis of ortho-(1-methylbut-2-en-1-yl)anilines, precursors of new cytotoxic heterocycles

Article abstract of DOI:10.1134/S1070363216040083

The reaction of aromatic Claisen rearrangement of N-(1-methylbut-2-en-1-yl)anilines in the presence of p-toluenesulfonic acid was investigated. N-Tosyl-2-(1-iodoethyl)-3-methylindoline derivatives were obtained; one of them exhibited a cytotoxic activity.

Full text of DOI:10.1134/S1070363216040083

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 4, pp. 810–814. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © L.A. Aleksandrova, M.F. Abdullin, Yu.V. Vakhitova, R.R. Gataullin, 2016, published in Zhurnal Obshchei Khimii, 2016, Vol. 86,
No. 4, pp. 622–626.
Approach to Preparative Synthesis
of ortho-(1-Methylbut-2-en-1-yl)anilines,
Precursors of New Cytotoxic Heterocycles
L. A. Aleksandrovaa, M. F. Abdullina, Yu. V. Vakhitovab, and R. R. Gataullina
a Ufa Institute of Chemistry of the Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Russia
е-mail: gataullin@anrb.ru
b Institute of Biochemistry and Genetics of Ufa Scientific Center, Ufa, Russia
Received July 28, 2015
Abstract—The reaction of aromatic Claisen rearrangement of N-(1-methylbut-2-en-1-yl)anilines in the presence
of p-toluenesulfonic acid was investigated. N-Tosyl-2-(1-iodoethyl)-3-methylindoline derivatives were obtained;
one of them exhibited a cytotoxic activity.
Keywords: halocyclization, indoles, alkenylanilines, cytotoxic activity, acid-catalyzed rearrangement
DOI: 10.1134/S1070363216040083
Some indole derivatives have been known to
possess high biological activity [1–5]. Benzopyrrole
derivatives may be modified by introduction of sub-
stituents into different positions of the heterocycle that
allows investigation of the structure–activity relation-
ship in several regioisomers. Therefore the synthesis of
new specimens of the series and investigation of their
biological activity attracted much attention of
researchers [6–10]. Among the numerous approaches
toward the synthesis of indole heterocycles [11–13] the
methods based on electrophilic intermolecular cycliza-
tion of ortho-alkenylanilines [14] are of particular
interest due to the possibility of preparation of a broad
spectrum of substituted benzopyrroles.
methylbut-2-en-1-yl)anilines; the target compounds
were the precursors of indoline derivatives (Scheme 1).
Biochemical investigations of the products of halo-
cyclization of tosylated pentenyl aniline 1a, namely
(2R*,3S*)-isomer of 3a, revealed a cytotoxic activity
towards HEK293 line (IC50 10.72 μM), HepG2 (IC50
40.83 μM), and Jurkat cells (IC50 14.96 μM). In this
regard, synthesis and investigation of cytotoxic activity
of such indole derivatives is a promising direction of
the search for new biologically important compounds.
The absence of a preparative synthesis of ortho-
pentenylaniline 4a (tosylate 1a precursor) was a
drawback of this approach. The compound might be
prepared by direct alkenylation of aniline with 1,3-
pentadiene in the presence of Lewis acids [15] or acid-
catalyzed aromatic Claisen amino rearrangement of N-
In the present work we report on the results of the
search for preparative method of the synthesis of 2-(1-
Scheme 1.
CH3
CH3
CH3
R
R
R
CH3
I
CH3
I
I2
CH3
+
K2CO3
CH2Cl2, 20oC
N
N
NHTs
Ts
2a−2c
Ts
3a−3c
1a−1c
R = H (a), CH3 (b), Cl (c).
810

APPROACH TO PREPARATIVE SYNTHESIS OF ortho-(1-METHYLBUT-2-EN-1-YL)ANILINES
811
Scheme 2.
NH2
NH2
NH
R2
NH2
R1
Br
R1
R1
TsOH
+
+
xylene
145oС, 5 h
R2
5а_5d
4а (86%)
4b (26%)
4c (68%)
4d (59%)
6а (0%)
6b (7%)
7 (10%)
R1 = R2 = H (a); R1 = Br, R2 = H (b); R1 = H, R2 = CH3 (c); R2 = Cl (d).
pentenylaniline 5a in the presence of HCl [16] or 0.2 N
H2SO4 [17]. Selectivity of compound 4a formation in
the acid-catalyzed rearrangements was higher [16, 17]
than in the case of direct alkenylation of aniline with
piperylene [15]. The catalyzed rearrangement of
compound 5a in the presence of HCl or H2SO4
proceeded at a temperature about 145°C and led to the
formation of two isomeric products of rearrangement,
4a and 6a, in overall yield about 82% in an
approximate ratio of 6 : 1 (Scheme 2). Isolation of
product 4a from the reaction mixture was done by
prolonged vacuum distillation using highly effective
rectification column or by the column chromatography
on aluminum oxide that of course reduced the
preparative value of the reaction.
significant increase in the biological activity of the
compound [19]. Aiming at further preparation of 5-
chlorosubstituted indolines 2c and 3c, we synthesized
compound 4d. Unlike alkenyl arylamine 5c, the
rearrangement of amine 5d in the presence of HCl or
p-TsOH did not proceed regioselectively. Along with
the formation of the target ortho-pentenylaniline 4d
the side-products of unidentified structure were
formed. Nevertheless, the acid-catalyzed rearrangement
of alkenyl arylamine followed by purification of the
reaction mixture by column chromatography on silica
gel proved to be the only approach to the synthesis of
compound 4d.
Tosylation of {4-chloro-2-[(2E)-1-methylbut-2-en-
1-yl]phenyl}amine 4d in pyridine led to the formation
of sulfonyl amide 1c. The reaction of compounds 1a–
1c with molecular iodine allowed the preparation of
(2R*,3R*)-indolines 2a [20], 2b [21], 2c, and
(2R*,3S*)-indolines 3a [19], 3b [20], and 3c (Scheme 1).
It should be noted that in the course of the reaction the
change in the ratio of the iodocyclization products was
observed depending on the nature of the substituent in
the para-position of the starting alkenylaniline. It was
found that in the case of R = CH3 the ratio of isomers
2b : 3b was ≈ 4 : 1 [21]. The absence of the substituent
(R = H) led to reducing the ratio (2а : 3а ≈ 2 : 1) [20].
Chlorine atom (R = Cl) possessing a negative
inductive (–I) and positive mesomeric (+M) effects
also promoted the change in the isomers ratio (2c : 3c ≈
2 : 3). Most probably it might be due to a significant
effect of variably activated aromatic ring on the
primary formation of two iodonium complexes.
To eliminate this drawback we used as acid an
equivalent amount of para-toluenesulfonic acid. The
reaction proceeded at reflux of the mixture of the
reagents in xylene and resulted in the formation of
ortho-isomer 4a in a high yield.
In the case of amine 5a the reaction proceeded
regioselectively. In contrast, ortho-bromosubstituted
analog 5b (prepared by the reaction of bromoaniline
with 3-chloropentene in Et3N) afforded ortho-4b and
para-6b isomers in a ratio 3.4 : 1 (Scheme 2).
Moreover, 2-bromoaniline and dipentenylated product 7
were detected in the reaction mixture (4b : 7 = 3.4 : 1.9).
When using para-toluidine 5c [18], the reaction led
to the formation of ortho-isomer 4c [16] (Scheme 2) as
well as to a significant amount of p-toluidine generated
due to decomposition of N-alkenyl tolylamine 5c.
1
It has been known that in some cases chlorine atom
In H NMR spectra of isomers 2 and 3 a distinct
in para-position of indole heterocycle favored a
differentiation of the proton signals at the key carbon
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 4 2016

812
ALEKSANDROVA et al.
atoms of the heterocyclic fragment of the molecule
was observed. Basing on the earlier obtained spectral
characteristics of analogs 2a, 2b and 3a, 3b [20, 21],
we attributed the signals of protons H2, H3, H1' and
methyl groups in the spectra of compounds 2c and 3c.
The data occurred to be slightly different as compared
with the earlier prepared compounds.
1H NMR spectrum, δ, ppm: 1.08 d (3Н, СН3, J =
7.0 Hz), 1.65 d.d (3Н, СН3, J = 4.8, 0.9 Hz), 2.39 s
(3Н, СН3), 3.05 q (1Н, Н1', J = 7.0 Hz), 5.23–5.37 m
(2Н, НС=СН), 6.61 s (1Н, NH), 7.08 d (1Н, Н3, J =
2.4 Hz), 7.14 d.d (1Н, Н5, J = 2.4, 8.4 Hz), 7.23 d (2Н,
Н3",5", J = 8.4 Hz), 7.35 d (1Н, Н6, J = 8.4 Hz), 7.58 d
(2Н, Н2",6", J = 8.4 Hz).
(2R*,3R*)-5-Chloro-2-[(1R*)-1-iodoethyl]-3-me-
thyl-1-[(4-methylphenyl)silfonyl]indoline (2c) and
(2R*,3S*)-5-chloro-2-[(1R*)-1-iodoethyl]-3-methyl-
1-[(4-methylphenyl)sulfonyl]indoline (3c). A mixture
of compound 1c (1.12 g, 3 mmol as a solution in
15 mL of methylene chloride), iodine (0.9 g, 3.6 mmol),
and K2CO3 (0.33 g) was stirred for 3 h at room
temperature. The reaction progress was monitored by
TLC eluting with benzene. After the reaction comple-
tion methylene chloride (25 mL), water (10 mL), and
5% solution of Na2S2O3 (15 mL) were added. The
organic layer was washed with water (10 mL), and
dried over MgSO4. After removing the solvent in a
vacuum the residue was crystallized from ethanol
The results of investigation of biological activity of
newly prepared heterocycles 2c and 3c based on halo-
substituted ortho-pentenylanilines will be reported
elsewhere.
In summary, the rearrangement of N-(1-methylbut-
2-en-1-yl)aniline catalyzed with p-TsOH proceeded
regioselectively with the formation of 2-(1-methylbut-
2-en-1-yl)aniline in a high yield while in the case of N-
(1-methylbut-2-en-1-yl)-2-bromo- or -4-chloroanilines
no regioselectivity was observed.
EXPERIMENTAL
1
IR spectra were recorded on a IRPresstige-21 spec-
trometer (Shimadzu). 1H and 13C NMR (CDCl3)
spectra were registered on a Bruker AM 300 instru-
ment operating at 300.13 and 75.73 MHz, internal
reference TMS. The product purity was monitored by
GLC on a Chrom-5 chromatograph; carrier gas helium
(50 mL/min), flame ionization detector, column
1200 × 3 mm, stationary phase liquid silicon SE-30
(5%) on a carrier Chromaton N-AW DMCS, working
temperature 50–300°С. Elemental analysis was carried
out on a CHNS Elemental Analyzer EURO EA-3000
instrument. Halogen content was determined by
burning the sample by Schoeniger method followed
with potentiometric titration. Column chromatography
was performed on MN Kisielgel 60 silica gel (40–
100 μM). TLC was done on Sorbfil plates (Sorbpolimer,
Krasnodar) with iodine vapors as a spots developer.
(15 mL). Compound 2c. Н NMR spectrum (CDCl3),
δ, ppm: 0.64 d (3H, CH3, J = 7.2 Hz), 2.01 d (3H, CH3,
J = 7.0 Hz), 2.37 s (3H, CH3), 3.07 d.q (1H, Н3, J =
3.5, 7.2 Hz), 3.34 d.d (1H, Н2, J = 3.0, 5.5 Hz), 4.48
d.q (1H, Н1', J = 5.5, 7.2 Hz), 6.99 d.d (1НAr, J = 1.6,
8.0 Hz), 7.22 d.d (1НAr, J = 1.6, 8.0 Hz), 7.23 d.d
(2НAr, J = 1.6, 8.0 Hz), 7.54 d (2НAr, J = 8.5 Hz), 7.62
1
d (1НAr, J = 8.5 Hz). Compound 3c. Н NMR spec-
trum (CDCl3), δ, ppm: 1.35 d (3H, CH3, J = 7.4 Hz),
1.78 d (3H, CH3, J = 7.2 Hz), 2.37 s (3H, CH3), 2.76
quintet (1H, Н3, J = 7.3 Hz), 4.34 d.q (1H, Н1', J = 4.4,
7.2 Hz), 4.55 d.d (1H, Н2, J = 4.4, 8.4 Hz), 6.89 t
(1НАr, J = 1.6 Hz), 7.17 d (1НAr, J = 7.9 Hz), 7.22 d.d
(1НAr, J = 1.6, 8.4 Hz), 7.50 d (2НAr, J = 8.4 Hz), 7.55
d (1НAr, J = 8.4 Hz).
{2-[(2E)-1-Methylbut-2-en-1-yl]phenyl}amine
(4a). A mixture of amine 5a (19 g, 0.118 mol), xylene
(70 mL), and p-TsOH (20.0 g, 0.118 mol) was stirred
at 145°C for 7 h. After cooling NaOH (7 g, 0.175 mol)
in water (70 mL) was added to the reaction mixture,
the mixture was thoroughly stirred and extracted with
tert-butyl methyl ether (200 mL). The organic layer
was dried over KOH and concentrated in a vacuum. To
separate aniline the residue was distilled at a
temperature of heating oil bath of 100°C then the bath
temperature was increased up to 145°C and amine 4a
was distilled off. Yield 16.5 g (86%), bp 102–104°C
(2 mmHg). Physicochemical characteristics were the
same as described earlier [17].
N-{4-Chloro-2-[(2E)-1-methylbut-2-en-1-yl]phenyl}-
4-methylbenzenesulfonamide (1c). A mixture of com-
pound 4d (1 g, 5.11 mmol) and TsCl (1.1 g, 5.77 mmol)
in 5 mL of anhydrous pyridine was stirred at 20°C for
17 h. Then it was diluted with 30 mL of water, stirred
for 20 min, and evaporated in a vacuum. Methylene
chloride (100 mL) and water (50 mL) were added to
the residue. The organic layer was washed with HCl
solution (50 mL, 5%) and water (20 mL), dried over
MgSO4, and concentrated in a vacuum. The residue
(1.724 g) was chromatographed eluting with C6H6.
Yield 1.47 g (85%). IR spectrum, ν, cm–1: 3276 (N–H).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 4 2016

APPROACH TO PREPARATIVE SYNTHESIS OF ortho-(1-METHYLBUT-2-EN-1-YL)ANILINES
813
(2-Bromophenyl)-[(2E)-1-methylbut-2-en-1-yl]
amine (5b). A mixture of 2-bromoaniline hydro-
bromide (49 g, 0.19 mol) with equivalent amount of
NaOH in 100 mL of water was stirred for 30 min. The
formed dark brown 2-bromoaniline was separated and
dissolved in 70 mL of Et3N. 2-Chloro-3-pentene (21 g,
0.2 mol) was added to the solution. The reaction
mixture was heated at 90°C for 3 h on a water bath. An
excess of Et3N was distilled off at a reduced pressure.
A solution of NaOH (20 g, 0.5 mol) in 100 mL of
water was added; the mixture was stirred and then
extracted with tert-butyl methyl ether (200 mL). The
organic layer was dried over KOH, filtered, and
concentrated at a reduced pressure. The residue was
distilled in a vacuum. Yield 30 g (65%), bp 111°С
(2 mmHg). IR spectrum, ν, cm–1: 3409 (N–H), 669
{2-Bromo-6-[(2E)-1-methylbut-2-en-1-yl]phenyl}-
amine (4b). Yield 7.8 g (26%). IR spectrum, ν, cm–1:
1
3455, 3378 (NH2), 678 (C–Br). Н NMR spectrum
(CDCl3), δ, ppm: 1.37 d (3Н, СН3, J = 7.0 Hz), 1.69 t.d
(3Н, СН3, J = 1.0, 3.9 Hz), 3.38–3.47 m (1Н, Н1'), 4.25
br.s (2Н, NН2), 5.51–5.57 m (2Н, Н2',3'), 6.64 t (1Н,
Н4, J = 7.9 Hz), 7.06 d.d (1Н, НAr, J = 1.1, 7.5 Hz),
7.33 d.d (1Н, НAr, J = 1.4, 7.9 Hz). 13С NMR spectrum
(CDCl3), δC, ppm: 17.83 and 19.44 (СH3), 38.17 (C1');
110.73, 131.02, 142.01 (C1,2,6); 119.06, 125.14, 126.01,
130.36, 134.40 (C3–5,2',3'). Mass spectrum, m/z (Irel, %):
239.0 (30) [M]+, 224.0 (15), 210.0 (20), 145.1 (100),
130.1 (50).
{2-Bromo-4-[(2E)-1-methylbut-2-en-1-yl]phenyl}-
amine (6b). Yield 2.0 g (7%). IR spectrum, ν, cm–1:
1
3471, 3380 (NH2), 678 (C–Br). Н NMR spectrum
1
(C–Br). Н NMR spectrum (CDCl3), δ, ppm: 1.34 d
(CDCl3), δ, ppm: 1.27 d (3Н, СН3, J = 7.0 Hz), 1.67 t.d
(3Н, СН3, J = 1.1, 6.1 Hz), 3.28 m (1Н, Н1'), 3.96 br.s
(2Н, NН2), 5.37–5.58 m (2Н, Н2',3'), 6.70 d (1Н, Н6,
J = 8.2 Hz), 6.95 d.d (1Н, Н5, J = 2.0, 8.2 Hz), 7.24 d
(1Н, Н3, J = 2.0 Hz). 13С NMR spectrum (CDCl3), δС,
ppm: 17.92 and 21.45 (СH3), 41.17 (C1'); 109.41,
137.97, 142.01 (C1,2,6); 133.17, 123.70, 127.21, 130.99,
133.17 (C3–5,2',3'). Mass spectrum, m/z (Irel, %): 239.03
(20) [M]+, 224.0 (12), 145.1 (100), 130.1 (30).
(3Н, СН3, J = 6.6 Hz), 1.69 d (3Н, СН3, J = 6.4 Hz),
3.91–4.01 m (1Н, Н1'), 4.27 d (1Н, NН, J = 5.0 Hz),
5.38–5.49 m and 5.58–5.72 m (2Н, Н2',3'), 6.54 d.t (1Н,
НAr, J = 1.3, 7.5 Hz), 6.64 d.d (1Н, НAr, J = 1.3,
8.2 Hz), 7.14 d.t (1Н, НAr, J = 1.3, 8.0 Hz), 7.41 d.d
(1Н, НAr, J = 1.4, 7.9 Hz).
N-(1-Methylbut-2-en-1-yl)-4-chloroaniline (5d)
was prepared similarly from 4-chloroaniline (6.3 g,
49 mol) and chloropentene (7.35 g). Yield 8.05 g
(84%), colorless liquid, bp 123–124°C (2 mmHg).
{2-Bromo-4,6-bis[(2E)-1-methylbut-2-en-1-yl]-
phenyl}amine (7). Yield 3.8 g (10%). IR spectrum, ν,
1
cm–1: 3445, 3375 (NH2), 678 (C–Br). Н NMR spec-
Rearrangement of alkenylaniline 5b. A mixture
of amine 5b (30 g, 0.125 mol), xylene (70 mL), and
p-TsOH (21.5 g, 0.125 mol) was stirred at heating
(140°C) on oil bath for 12 h. After cooling to room
temperature a solution of NaOH (7 g, 0.175 mol) in
70 mL of H2O was added, the mixture was thoroughly
stirred, and then extracted with tert-butyl methyl ether
(200 mL). The organic layer was separated, dried over
KOH, and concentrated at a reduced pressure. The
residue was distilled in a vacuum to get 2-bromo-
aniline (6 g, 28%), bp 60°C (2 mmHg), about 2 g of a
mixture of 2-bromoaniline, amine 4b, and para-isomer
of compound 6b in a ratio of 1 : 25 : 9, and
approximately 10 g of a mixture of compounds 4b and
6b. The still bottoms contained compound 7.
Purification of 10 g of the mixture of compounds 4b
and 6b by chromatography on a column filled with
280 g of silica gel provided amines 4b (7.8 g, 26%,
eluent – petroleum ether) and 6b (2 g, 7%, eluent –
benzene). Compound 7 (3.8 g, 10%) was isolated by
chromatographic purification of the still bottoms on
silica gel (eluent benzene).
trum (CDCl3), δ, ppm: 1.28 d (3Н, СН3, J = 7.0 Hz),
1.37 d (3Н, СН3, J = 7.0 Hz), 1.68 d (3Н, СН3, J =
5.9 Hz), 1.70 d (3Н, СН3, J = 6.0 Hz), 3.24–3.44 m
(2Н, Н1',1''), 4.11 br.s (2Н, NН2), 5.38–5.60 m (4Н,
Н
2',3',2'',3''), 6.88 d (1Н, Н3, J = 1.8 Hz), 7.16 d (1Н, Н5,
J = 1.8 Hz). 13С NMR spectrum (CDCl3), δС, ppm:
17.80, 19.35, 17.80, 21.51 (СH3); 38.41, 41.43 (C1',1'');
110.82, 130.83, 137.34, 139.88 (C1,2,4,6); 123.46, 124.93,
125.11, 128.53, 134.49, 136.23 (C3,5,2',3',2'',3''). Mass
spectrum, m/z (Irel, %): 307.1 (40) [M]+, 224.0 (36), 144.1
(30), 69.1 (100).
{4-Methyl-2-[(2E)-1-methylbut-2-en-1-yl]phenyl}-
amine (4c) was prepared similarly from amine 5c (3.5 g,
20 mmol) and p-TsOH (3.4 g, 20 mmol). Yield 2.4 g
(68%). Physicochemical characteristics were the same
as described in [16].
{4-Chloro-2-[(2E)-1-methylbut-2-en-1-yl]phenyl}-
amine (4d). a. Gaseous HCl was bubbled through a
solution of compound 5d (4.89 g, 25 mmol) in 20 mL
of xylene for 30 min. Then the reaction mixture was
heated under reflux for 5 h, cooled to room tem-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 4 2016

814
ALEKSANDROVA et al.
6. Muzalevskiy, V.M., Nenajdenko, V.G., Shastin, A.V.,
Balenkova, E.S., and Haufe, G., Tetrahedron, 2009,
vol. 65, p. 7553. DOI: 10.1016/j.tet.2009.06.120.
perature, and treated with a solution of NaOH (4 g,
100 mmol) in 50 mL of water. The product of the
reaction was extracted with tert-butyl methyl ether.
The organic layer was dried over MgSO4 and
concentrated in a vacuum. The residue was purified by
chromatography eluting with petroleum ether. Yield
2.9 g (59%), bp 121–126°С (2 mmHg). IR spectrum, ν,
7. Lyakhovnenko, A.S., Red’ko, T.S., Aksenova, I.V.,
Aksenov, N.A., and Aksenov, A.V., Russ. J. Org.
Chem., 2013, vol. 49, p. 1244. DOI: 10.1134/
S1070428013080277.
1
cm–1: 3416, 3374 (NH2), 490 (C–Cl). Н NMR spec-
8. Inamoto, K., Saito, T., Hiroya, K., and Doi, T., Synlett,
2008, p. 3157. DOI: 10.1055/s-0028-10874131.
trum (CDCl3), δ, ppm: 1.35 d (3Н, СН3, J = 7.0 Hz),
1.69 d (3Н, СН3, J = 4.0 Hz), 3.30–3.40 m (1Н, Н1'),
3.69 br.s (2Н, NН2), 5.49–5.52 m (2Н, Н2',3'), 6.59 d
(1Н, Н6, J = 8.4 Hz), 6.99 d.d (1Н, Н5, J = 2.4,
8.4 Hz), 7.06 d (1Н, Н3, J = 2.4 Hz). 13С NMR
spectrum (CDCl3), δС, ppm: 17.77 and 19.24 (СH3),
37.00 (C1'); 117.02, 124.93, 126.58, 126.73, 134.10
(C3,5,6,2',3'); 123.37, 131.37, 142.78 (C1,2,4).
9. Penoni, A. and Nicholas, K.M., Chem. Commun., 2002,
p. 484. DOI: 10.1039/b110370a.
10. Uchuskin, M.G., Molodtsova, N.V., Abaev, V.T.,
Trushkov, I.V., and Butin, A.V., Tetrahedron, 2012,
vol. 68, p. 4252. DOI: 10.1016/j.tet.2012.03.069.
11. Smirnov, A.N., Aksenov, N.A., Malikova, I.V., and
Aksenov, A.V., Chem. Heterocycl. Compd., 2014,
vol. 50, p. 594. DOI: 10.1007/s10593-014-1514-3.
12. Dalpozzo, R., Chem. Soc. Rev., 2015, vol. 44, p. 742.
b. The reaction of amine 5d (3 g, 15.3 mmol) with
TsOH (2.64 g, 15.3 mmol) was performed according to
the method for preparation of compound 4a. Yield
1.7 g (57%).
DOI: 10.1039/c4cs00209a.
13. Butin, A.V., Smirnov, S.K., Tsiunchik, F.A., Uchus-
kin, M.G., and Trushkov, I.V., Synthesis, 2008, p. 2943.
DOI: 10.1055/s-2008-1067248.
14. Gataullin, R.R., Vestn. SPbGU, Ser. 4: Fizika. Khimiya,
ACKNOWLEDGMENTS
2014, vol. 1, no. 1, p. 51.
This work was done with the use of equipment of
the Centre of Joint Use “Khimiya” of Ufa Institute of
Chemistry of the Russian Academy of Sciences.
15. Gataullin, R.R., Kazhanova, T.V., Sagitdinov, I.A.,
Galyautdinov, A.A., Fatykhov, A.A., Spirikhin, L.V.,
and Abdrakhmanov, I.B., Russ. J. Appl. Chem., 2001,
vol. 74, no. 2, p. 280. DOI: 10.1023/A:1012790605083.
16. Sharafutdinov, V.M., Cand. Sci. (Chem.) Dissertation,
REFERENCES
Ufa, 1982.
1. Higuchi, K., and Kawasaki, T., Nat. Prod. Rep., 2007,
17. Jolidon, S., and Hansen, H.-J., Helv. Chim. Acta, 1979,
vol. 24, p. 843. DOI: 10.1039/B516351J.
vol. 62, p. 2581. DOI: 10.1002/hlca.19790620812.
2. Gudmundsson, K.S., Sebahar, P.R., D’Aurora,
Richardson L., Catalano, J.G., Boggs, S.D., Spalte-
nstein, A., Sethna, P.B., Brown, K.W., Harvey, R., and
Romines, K.R., Bioorg. Med. Chem. Lett., 2009, vol. 19,
p. 3489. DOI: 10.1016/j.bmcl.2009.05. 003.
18. Abdrakhmanov, I.B., Sharafutdinov, V.M., Dzhemi-
lev, U.M., Tal’vinskii, E.V., and Tolstikov, G.A., Zh.
Prikl. Khim., 1982, vol. 49, no. 9, p. 2121.
19. Boggs, S.D., Cobb, J.D., Gudmundson, K.S., Jones, L.A.,
Matsuoka, R.T., Millar, A., Patterson, D.E., Samano, V.,
Trone, M.D., Xie, S., and Zhou, X.M., Org. Proc. Res.
Develop., 2007, vol. 11, p. 539. DOI: 10.1021/op060223v.
3. Brancale, A., and Silvestri, R., Med. Res. Rev., 2007,
vol. 27, p. 209. DOI: 10.1002/med.20080.
20. Mazgarova, G.G., Suponitskii, K.Yu., and Gataul-
lin, R.R., Russ. J. Org. Chem., 2013, vol. 49, p. 1322.
DOI: 10.1134/S1070428013090133.
4. O’Connor, S.E. and Maresh, J., Nat. Prod. Rep., 2006,
vol. 23, p. 532. DOI: 10.1039/B512615K.
5. Simonov, A.Yu., Lakatosh, S.A., Luzikov, Yu.N.,
Reznikova, M.I., and Preobrazhenskaya, M.N., Russ.
Chem. Bull., 2010, vol. 59, p. 1442. DOI: 10.1007/
s11172-010-0260-7.
21. Mazgarova, G.G., Absalyamova, A.M., and Gataul-
lin, R.R., Russ. J. Org. Chem., 2012, vol. 48, no. 9,
p. 1200. DOI: 10.1134/S1070428012090096.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 4 2016