Synthesis of Potentially Bioactive 6-Bromobenzo[f]isoindolinium Bromides by Base-Catalyzed Intramolecular [4+2]-Cycloaddition

Article abstract of DOI:10.1134/S1070428018080067

Intramolecular cyclization of bromides of diethyl-, dipropyl-, and penthamethylenepropargyl[3-(4-bromophenyl)prop-2-ynyl]ammonium into 6-bromobenzo[f]isoindolinium bromides catalyzed with bases occurs with moderate self-heating. The morpholine analog even

Full text of DOI:10.1134/S1070428018080067

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 8, pp. 1156–1160. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © E.О. Chukhadzhian, H.R. Gevorgyan, L.V. Ayrapetyan, El.О. Chukhadzhian, K.G. Shahkhatuni, А.S. Mkrtchyan, G.А. Panosyan,
2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54, No. 8, pp. 1147–1151.
Synthesis of Potentially Bioactive 6-Bromobenzo[f]isoindolinium
Bromides by Base-Catalyzed Intramolecular [4+2]-Cycloaddition
E. О. Chukhadzhiana, H. R. Gevorgyana,c, L. V. Ayrapetyana, El. О. Chukhadzhiana,
K. G. Shahkhatunia, А. S. Mkrtchyana, and G. А. Panosyanb*
a Institute of Organic Chemistry of Scientific Technological Center of Organic and Pharmaceutical Chemistry of National
Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
*e-mail: hasulik4@mail.ru
b Molecular Structure Research Center of Scientific Technological Center of Organic and Pharmaceutical Chemistry
of National Academy of Sciences of Armenia, Yerevan, 0014 Armenia
c National Polytechnical University of Armenia, Yerevan, 0009 Armenia
Received December 14, 2017
Abstract—Intramolecular cyclization of bromides of diethyl-, dipropyl-, and penthamethylenepropargyl[3-(4-
bromophenyl)prop-2-ynyl]ammonium into 6-bromobenzo[f]isoindolinium bromides catalyzed with bases
occurs with moderate self-heating. The morpholine analog even in more diluted solutions reacts with vigorous
self-heating. Cyclization of dimethyl analog takes place only at heating at 80–85°С during 1 h.
DOI: 10.1134/S1070428018080067
Research on the synthesis of nitrogen- and oxygen-
containing heterocyclic compounds is one of important
tasks of organic chemistry. Besides an obvious
theoretical interest they possess a practical value: they
are present in the composition of antibiotics, alkaloids,
proteins, cordial glycosides, etc. There is only scarse
information on compounds of isoindolinium series and
their condensed analogs that may be due to the
difficulty of their preparation methods.
This study along with the practical has a theoretical
issue: the data, obtained in the course of investigation,
may confirm the mechanism we previously have
suggested for the base-catalyzed intramolecular
cyclization reaction [3, 6].
To this end we synthesized dialkyl [3-(4-bromophe-
nyl)prop-2-ynyl]amines 1a–1e, alkylation of which with
propargyl bromide in acetonitrile or diethyl ether provided
dialkylpropargyl[3-(4-bromophenyl)prop-2-ynyl]ammo-
nium bromides 2a–2e in almost quantitative yields.
Base-catalyzed intramolecular [4+2]-cycloaddition
of ammonium salts, containing π2-group along with
different π4-fragments, is a new direction in organic
chemistry and provides great possibilities for the syn-
thesis of biologically active di-, tri-, polycyclic isoindol-
inium and tetrahydro-1Н-isoindolium salts [1–3].
As a result of cyclization of salts 2a–2e 2,2-dialkyl-
6-brombenzo[f]isoindolinium bromides 3a–3e are
formed in 85–98% yields (see the scheme). The
structure of the initial amines 1а–1е, salts 2а–2е, and
products of their cyclization 3а–3е was established by
IR and 1Н, 13С NMR spectroscopy.
As known, dialkylpropargyl[3-(4-chlorophenyl)-
prop-2-ynyl]ammonium bromides [4] as compared to
3-phenylprop-2-ynyl analogs [5] undergo [4+2]-
cycloaddition in milder conditions (molar ratio salt–
alkali 10 : 1), forming biologically active 6-chloro-
benzo[f]isoindolinium bromides.
Salts 2a–2e undergo cyclization along the cycliza-
tion mechanism that we have previously suggested
basing on the data of IR spectroscopy [6, 7], and
experimental data from [3, 8, 9], according to which
the enyne fragment is directly involved into intra-
molecular cyclization as π4-fragment, and alkali is the
driving force of the cyclization that includes an
electron transfer by six-membered cyclic mechanism
of counter clockwise direction [3].
Extending and developing the area of base-cata-
lyzed intramolecular cyclization we brought in the reaction
in this study quaternary ammonium salts, containing pro-
pargyl group along with 3-(4-bromophenyl)prop-2-ynyl.
1156

SYNTHESIS OF POTENTIALLY BIOACTIVE 6-BROMOBENZO[f]ISOINDOLINIUM
1157
R
H
+
Br
Br
N
R
R
+
+
R'
N
N
Br
Br_
R'
R'
Br_
Br_
_OH
2a_2e
3a_3e
R = R' = Me (a), Et (b), Pr (c); R,R' = (CH2)5 (d), (CH2)2O(CH2)2 (e).
The effect on the cyclization of substituents at the
nitrogen atom and at the aromatic ring was discovered.
So, the cyclization of [3-(4-bromophenylprop-2-ynyl)]-
dimethylpropargylammonium bromide 2а in the
presence of 0.2 mol of alkali per 1 mol of initial salt
occurs at heating of reaction mixture at 80–85°С
during 1 h. Meanwhile, the cyclization of 3-(4-
chlorophenyl)prop-2-ynyl analog proceeds at room
temperature [4]. The cyclization of salts 2b–2d in the
same conditions occurs with self-heating. Because of
the poor solubility of salt 2е in water the cyclization
was performed in diluted solution in the presence of
ethanol. Even in these conditions the cyclization of salt
2е occurs with self-heating.
less electro-negativity of bromine atom compared to
chlorine atom, which hampers the cyclization by six-
membered cyclic mechanism.
EXPERIMENTAL
IR spectra of amines 1a–1e (thin layer) and salts
2a–2e (films from chloroform), 3a–3e (mineral oil)
were registered on a spectrophotometer Specord 75 IR.
13
1Н and C NMR spectra were recorded on a spectro-
meter Mercury-300VX Varian (300 and 75 МHz respec-
tively) in DMSO-d6–CCl4. Chemical shifts were measured
from internal reference TMS. Elemental analysis was
carried out on an analyzer vario MICRO cube. Melting
points of salts were established on an instrument VEB
Wägetechnik Rapido Radebeul Betriebdes. Purity of
cyclic salts was monitored by TLC on Silufol UV-254
plates, eluent 1-BuOH–EtOH–H2O–AcOH, 10 : 2 : 1 : 5,
development with iodine vapor.
The obtained experimental data agree well with the
results of the kinetic study previously performed by
Babayan et al. [10, 11] for establishing the cyclization
mechanism, and also with the cyclization mechanism
that we suggested [3, 6].
Amines 1a–1e were obtained by methods [4, 12].
Hence at increasing volume of alkyl substituent or
the presence of piperidinium cycle the positive charge
of nitrogen atom is mostly neutralized, providing
easier electron transfer in the cyclization (see the
scheme) [3, 6]. At the cyclization of salt 2е because of
the lone electron pair of oxygen atom of morpholinium
fragment the positive charge of nitrogen atom is to a
large extent neutralized, therefore self-heating occurs
even in dilute solution.
Dimethyl[3-(4-bromophenyl)prop-2-ynyl]amine
(1a). Into a metal cylinder was placed 2.1 g (70 mmol)
of paraformaldehyde, 30 mL of dioxane was added,
and then was charged 12.7 g (70 mmol) of 4-bromo-
phenylacetylene [13] in 25 mL of dioxane, 3.15 g
(70 mmol) of dimethylamine, dissolved in 30 mL of
dioxane, 0.3 g of iron chloride, and 0.3 g of copper
diacetate. The reaction mixture was heated for 60–65 h
at 90–95°С, then acidified with 25% solution of HCl to
acid reaction. At low pressure the solvent was distilled
off. The reaction mixture and the distillate were treated
with diethyl ether to remove unreacted 4-bromo-
phenylacetylene, and the reaction mixture was
alkalinized with 20% solution of NaОН. The reaction
product was extracted with ether (3 × 70 mL), the ether
extract was dried with MgSO4. After distilling off the
ether amine 1a was isolated by vacuum distillation.
Yield 6.66 g (40%), bp 122°C (3 mmHg), n2D0 1.5820,
mp of picrate 142°C (from anhydrous EtOH). IR
spectrum, ν, cm–1: 3050, 3020, 1580 (aromatic ring),
720, 820 (p-substituted benzene ring). 1Н NMR
In favor of the above said contribute also the data
of kinetic investigations, according to which the rate of
cyclization of propargyl(3-phenylpropargyl)morpholi-
nium bromide significantly exceeds the rate of
cyclization of other analogs [11].
The cyclization of salts 2b–2d occurs with mode-
rate self-heating at the application of even 0.2 mol of
alkali per 1 mol of initial salt, compared to 3-(4-
chlorophenyl)prop-2-ynyl analogs, cyclization of
which, excluding dimethyl analog, occurs with active
self-heating already in the presence of 0.1 mol of alkali
per 1 mol of initial salt [4]. This can be explained by
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CHUKHADZHIAN et al.
1158
spectrum, δ, ppm: 2.28 s (6Н, СН3), 3.40 s (2Н, СН2),
7.27–7.31 m (2Н) and 7.43–7.47 m (2Н, С6Н4). 13С
NMR spectrum, δ, ppm: 43.4 (2СН3), 47.7 (СН2),
83.6, 85.7 (C≡C), 121.3, 121.7, 130.9 (2СН), 132.6
(2СН). Found, %: C 55.21; H 5.19; Br 33.83; N 5.75.
C11H12BrN. Calculated, %: C 55.46; H 5.04; Br 33.61;
N 5.88.
C6H4). 13C NMR spectrum, δ, ppm: 23.4 (CH2), 25.2
(2CH2), 47.6 (NCH2), 52.5 [N(CH2)2], 83.3, 86.3 (C≡C),
121.2, 121.8, 130.9 (2CH), 132.6 (2CH). Found, %: C
60.21; H 5.35; Br 29.08; N 5.16. C14H16BrN.
Calculated, %: C 60.43; H 5.50; Br 28.78; N 5.03.
[3-(4-Bromophenyl)prop-2-ynyl]morpholine
(1е). Yield 7.85 g (51%), bp 172–174°C (4–5 mmHg),
n2D0 1.5898, mp 43–44°C (crystallizes at room
temperature), mp of picrate 180–183°C (anhydrous
EtOH). IR spectrum, ν, cm–1: 3030, 1580 (aromatic
ring), 800 (p-substituted benzene ring). 1Н NMR
spectrum, δ, ppm: 2.51–2.55 m [4Н, N(CH2)2], 3.44 s
(2Н, CH2C≡C), 3.61–3.65 m [4Н, О(CH2)2], 7.28–7.32
m (2H) and 7.43–7.48 m (2H, C6H4). 13C NMR
spectrum, δ, ppm: 47.2 (NCH2), 51.6 [N(CH2)2], 65.8
[О(CH2)2], 83.7, 85.5 (C≡C), 121.4, 121.6, 131.0
(2CH), 132.6 (2CH). Found, %: C 55.41; H 5.14; Br
28.86; N 4.88. C13H14BrNО. Calculated, %: C 55.71;
H 5.00; Br 28.57; N 5.00.
Compounds (1b–1e). General method. A mixture of
1.65 g (55 mmol) of paraformaldehyde, 10 g (55 mmol)
of 4-bromophenylacetylene, 55 mmol of the corres-
ponding secondary amine dissolved in 100 mL of
dioxane, 0.3 g of iron chloride, 0.2 g of copper diacetate
were heated at reflux for 60–65 h at 90–95°С, then
worked up similarly to the synthesis of amine 1a.
[3-(4-Bromophenyl)prop-2-ynyl]diethylamine
(1b). Yield 6.6 g (45%), bp 145°C (2 mmHg), n2D0
1.5631, mp of picrate 185–188°C (anhydrous EtOH).
IR spectrum, ν, cm–1: 3030, 1500 (aromatic ring), 800
1
(p-substituted benzene ring). Н NMR spectrum, δ,
ppm: 1.06 t (6Н, СН3, J 7.2 Hz), 2.53 q (4Н, CH2CH3,
J 7.2 Hz), 3.54 s (2Н, CH2C≡C), 7.24–7.29 m (2H)
and 7.42–7.46 m (2H, C6H4). 13C NMR spectrum, δ,
ppm: 12.2 (2CH3), 40.6 (CH2), 46.5 (2CH2), 83.2, 85.7
(C≡C), 121.2, 121.8, 130.8 (2CH), 132.6 (2CH). Found,
%: C 58.42; H 6.16; Br 30.33; N 5.14. C13H16BrN.
Calculated, %: C 58.65; H 6.01; Br 30.08; N 5.26.
In all reactions also the initial 4-bromophenyl-
acetylene was isolated in 5–10% yield.
Salts 2a–2e were obtained in almost quantitative
yields by reaction of 5 mmol of amines 1a–1e with
10 mmol of propargyl bromide in 4–5 mL of
acetonitrile (2b–2e) or in 10 mL of anhydrous ethyl
ether (2a). At room temperature white crystalline salts
2а, 2b, and 2d–2e precipitated, at the preparation of
salt 2c acetonitrile was distilled off at low pressure, the
salt was washed with anhydrous ether.
[3-(4-Bromophenyl)prop-2-ynyl]dipropylamine
(1c). Yield 7.76 g (48%), bp 150–152°C (3–4 mmHg),
n2D0 1.5525, mp of picrate 132–134°C (anhydrous
EtOH). IR spectrum, ν, cm–1: 3030, 1480 (aromatic
ring), 800 (p-substituted benzene ring). 1Н NMR
spectrum, δ, ppm: 0.91 t (6Н, СН3, J 7.4 Hz), 1.40–
1.53 m (4Н, CH2CH3), 2.40–2.45 m [4Н, N(CH2)2],
3.52 s (2Н, CH2C≡C), 7.24–7.28 m (2H) and 7.41–
[3-(4-Bromophenyl)prop-2-ynyl]dimethylpro-
pargylammonium bromide (2a). Yield 1.77 g (99%),
white crystals, mp 183–185°C (anhydrous EtOH). IR
spectrum, ν, cm–1: 3020, 3010, 1800 (aromatic ring),
2220 (disubstituted acetylene bond), 2130 (monosubs-
tituted acetylene bond), 840–810 (p-substituted
13
7.46 m (2H, C6H4). C NMR spectrum, δ, ppm: 11.4
(2CH3), 20.1 (2CH2), 41.8 (NCH2), 55.0 [N(CH2)2],
83.2, 86.0 (C≡C), 121.2, 121.9, 130.9 (2CH), 132.6
(2CH). Found, %: C 60.96; H 6.94; Br 27.51; N 4.63.
C15H20BrN. Calculated, %: C 61.22; H 6.80; Br 27.21;
N 4.76.
1
benzene ring). Н NMR spectrum, δ, ppm: 3.41 s (6Н,
CH3), 3.80 t (1Н, ≡CH, J 2.5 Hz), 4.78 d (2H,
CH2C≡CH, J 2.5 Hz), 4.92 s (2H, CH2C≡C), 7.55 s
13
(4H, C6H4). C NMR spectrum, δ, ppm: 49.2 (2CH3),
53.1 (NCH2), 53.7 (NCH2), 71.5 (≡C), 77.9 (≡C), 82.8
(≡CH), 89.6 (≡C), 119.4, 123.2, 131.2 (2CH), 133.4
(2CH). Found, %: C 47.35; H 4.05; Br 44.57; N 4.05.
C14H15Br2N. Calculated, %: C 47.06 H 4.20; Br 44.82;
N 3.92.
[3-(4-Bromophenyl)prop-2-ynyl]piperidine (1d).
Yield 6.27 g (41%), bp 175–177°C (4–5 mmHg), n2D0
1.5876, mp 38–40°C (crystallizes at room
temperature), mp of picrate 197°C (anhydrous EtOH).
IR spectrum, ν, cm–1: 3060, 1590 (aromatic ring), 850,
1
[3-(4-Bromophenyl)prop-2-ynyl]propargyl-
diethylammonium bromide (2b). Yield 1.83 g (95%),
white crystals, mp 152–154°C (anhydrous EtOH). IR
spectrum, ν, cm–1: 3120, 1600 (aromatic ring), 2220
810 (p-substituted benzene ring). Н NMR spectrum,
δ, ppm: 1.38–1.46 m (2Н, СН2), 1.55–1.62 m (4Н,
2СН2), 2.45–2.51 m [4Н, N(CH2)2], 3.39 s (2Н,
CH2C≡C), 7.26–7.31 m (2H) and 7.42–7.47 m (2H,
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SYNTHESIS OF POTENTIALLY BIOACTIVE 6-BROMOBENZO[f]ISOINDOLINIUM
1159
(disubstituted acetylene bond), 2100 (monosubstituted
acetylene bond), 810 (p-substituted benzene ring). Н
spectrum, δ, ppm: 3.78–3.85 m [4Н, O(CH2)2], 3.87 t (1Н,
≡CH, J 2.4 Hz), 4.04–4.10 m [4Н, N(CH2CH2)2O],
4.92 d (2H, CH2C≡CH, J 2.4 Hz), 5.04 s (2H,
CH2C≡C), 7.52–7.61 m (4H, C6H4). Found, %: C
47.87; H 4.11; Br 40.40; N 3.71. C16H17Br2NО.
Calculated, %: C 48.12; H 4.26; Br 40.10; N 3.51.
1
NMR spectrum, δ, ppm: 1.44 t (6Н, CH3, J 7.1 Hz),
3.68 q (4Н, CH2CH3, J 7.1 Hz), 3.81 t (1Н, ≡CH, J
2.5 Hz), 4.64 d (2H, CH2C≡CH, J 2.5 Hz), 4.77 s (2H,
CH2C≡C), 7.54 s (4H, C6H4). 13C NMR spectrum, δ,
ppm: 7.9 (2C, CH3), 48.5 (NCH2), 49.1 (NCH2), 54.6
(2C, CH2CH3), 71.2 (≡C), 77.7 (≡C), 82.6 (≡CH), 89.2
(≡C), 119.3, 123.1, 131.2 (2CH), 133.4 (2CH). Found,
%: C 50.16; H 5.09; Br 41.26; N 3.52. C16H19Br2N.
Calculated, %: C 49.87; H 4.93; Br 41.56; N 3.64.
2,2-Dimethyl-6-bromobenzo[f]isoindolinium
bromide (3a). To a solution of 3 mmol of salt 2а in
2.8 mL of water was added 0.2 mL of 3 N solution of
KОН (molar ratio salt–base 5 : 1) and the mixture was
heated for 1 h at 80–85°С. After cooling the mixture
was extracted with diethyl ether to remove possible
admixtures, then the precipitate was filtered off. Yield
0.9 g (85%), white crystals, mp 255°C (H2O). IR
spectrum, ν, cm–1: 3030, 1580 (aromatic ring), 890,
[3-(4-Bromophenyl)prop-2-ynyl]propargyldipro-
pylammonium bromide (2c). Yield 1.96 g (95%),
white crystals, mp 142°C (anhydrous EtOH). IR
spectrum, ν, cm–1: 2220 (disubstituted acetylene bond),
2100 (monosubstituted acetylene bond), 1600, 1580
1
825 (1,2,4- and penta-substituted benzene ring). Н
1
(aromatic ring), 810 (p-substituted benzene ring). Н
NMR spectrum, δ, ppm: 3.50 s (6Н, CH3), 5.16 br.s
(2H, NCH2), 5.18 br.s (2H, NCH2), 7.59 dd (1H, =CH,
C6H3, J 8.7, 2.0 Hz), 7.86 d (1H, =CH, C6H3, J 8.7 Hz),
7.94 s (1H, =CH, C6H2), 7.99 s (1H, =CH, C6H2), 8.12
d (1H, =CH, C6H3, J 2.0 Hz). 13C NMR spectrum, δ,
ppm: 51.2 (2C, CH3), 68.8 [2C, N(CH2)2], 119.8 (CH),
121.5 (CH), 122.4 (CH), 129.3 (CH), 129.5 (CH),
129.7 (CH), 131.2, 132.2, 132.9, 133.9. Found, %: C
47.41; H 4.02; Br 44.45; N 4.11. C14H15Br2N.
Calculated, %: C 47.06; H 4.20; Br 44.82; N 3.92.
NMR spectrum, δ, ppm: 1.04 t (6Н, CH3, J 7.2 Hz),
1.81–1.95 m (4Н, CH2CH3), 3.50–3.58 m [4Н, N(CH2)2],
3.80 t (1Н, ≡CH, J 2.3 Hz), 4.68 d (2H, CH2C≡CH, J
2.3 Hz), 7.54 s (4H, C6H4). 13C NMR spectrum, δ,
ppm: 10.4 (2CH3), 15.5 (2CH2), 49.7 (NCH2), 50.2
(NCH2), 60.9 [N(CH2)2], 71.3 (≡C), 77.8 (≡C), 82.6
(≡CH), 89.4 (≡C), 119.3, 123.1, 131.2 (2CH), 133.3
(2CH). Found, %: C 52.62; H 5.73; Br 38.38; N 3.11.
C18H23Br2N. Calculated, %: C 52.30; H 5.57; Br 38.74;
N 3.39.
Compounds 3b–3d. General method. To a
solution of 3 mmol of salt 2b–2d in 2 mL of water was
added 0.2 mL of 3 N solution of KОН (molar ratio salt–
base 5 : 1). After 3–4 min the temperature of reaction
mixture raised from 25°C to 65–70°С. Cyclic salt 3d
was isolated from reaction mixture by filtration. At the
preparation of salts 3b and 3c after cooling the reaction
mixture was treated with ethyl ether to remove
possible admixtures and acidified with aqueous
solution of HBr. The solvent was distilled off till
dryness at low pressure. From the residue the organic
salt was extracted by anhydrous ethanol. From alcohol
solution cyclic salts 3b and 3c were precipitated by
adding ethyl ether.
[3-(4-Bromophenyl)prop-2-ynyl]propargylpipe-
ridinium bromide (2d). Yield 1.94 g (98%), white
crystals, mp 153–155°C (anhydrous EtOH). IR
spectrum, ν, cm–1: 3050, 1580 (aromatic ring), 2240
(disubstituted acetylene bond), 2100 (monosubstituted
1
acetylene bond), 840 (p-substituted benzene ring). Н
NMR spectrum, δ, ppm: 1.65–1.77 m (2Н, CH2), 1.94–
2.03 m (4Н, 2CH2), 3.78–3.83 m [5Н, ≡CH, N(CH2)2],
4.77 d (2H, CH2C≡CH, J 2.5 Hz), 4.89 s (2H,
CH2C≡C), 7.55 s (4H, C6H4). 13C NMR spectrum, δ,
ppm: 19.1 (2CH2), 20.1 (CH2), 49.4 (NCH2), 50.4
(NCH2), 57.4 [N(CH2)2], 71.0 (≡C), 77.4 (≡C), 82.9
(≡CH), 89.5 (≡C), 119.4, 123.1, 131.1 (2CH), 133.4
(2CH). Found, %: C 51.68; H 4.95; Br 40.04; N 3.40.
C17H19Br2N. Calculated, %: C 51.38; H 4.79; Br 40.30;
N 3.53.
2,2-Diethyl-6-bromobenzo[f]isoindolinium
bromide (3b). Yield 1.0 g (87%), white crystals, mp
203–205°C (anhydrous EtOH). IR spectrum, ν, cm–1:
3030, 1580 (aromatic ring), 870, 805 (1,2,4- and penta-
[3-(4-Bromophenyl)prop-2-ynyl]propargylmor-
pholinium bromide (2e). Yield 1.91 g (96%), white
crystals, mp 128–130°C (anhydrous EtOH). IR spectrum,
ν, cm–1: 3030, 1580 (aromatic ring), 2220 (disubstitu-
ted acetylene bond), 2100 (monosubstituted acetylene
bond), 860, 820 (p-substituted benzene ring). 1Н NMR
1
substituted benzene ring). Н NMR spectrum, δ, ppm:
1.35 t (6Н, CH3, J 7.1 Hz), 3.73 q (4Н, CH2CH3, J
7.1 Hz), 5.17 br.s (2H, NCH2), 5.20 br.s (2H, NCH2),
7.57 d.d (1H, =CH, C6H3, J 8.7, 1.8 Hz), 7.86 d (1H,
=CH, C6H3, J 8.7 Hz), 7.89 s (1H, =CH, C6H2), 7.94 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 8 2018

CHUKHADZHIAN et al.
1160
(1H, =CH, C6H2), 8.12 d (1H, =CH C6H3, J 1.8 Hz).
13C NMR spectrum, δ, ppm: 8.7 (2C, CH3), 55.6 (2C,
CH2CH3), 65.4 [2C, N(CH2)2], 119.7, 120.8 (CH),
121.7 (CH), 129.2 (CH), 129.5 (CH), 129.6 (CH),
131.3, 132.3, 133.0, 133.9. Found, %: C 50.21; H 4.75;
Br 41.22; N 3.84. C16H19Br2N. Calculated, %: C 49.87;
H 4.93; Br 41.56; N 3.64.
259°C (EtOH). IR spectrum, ν, cm–1: 3030, 1590
(aromatic ring), 880, 810 (1,2,4- and penta-substituted
1
benzene ring). Н NMR spectrum, δ, ppm: 3.82–3.87
m [4Н, O(CH2)2], 4.06–4.11 m [4Н, (CH2CH2)2O],
5.38 br.s (2H, NCH2), 5.40 br.s (2H, NCH2), 7.58 d.d
(1H, =CH, C6H3, J 8.7, 2.0 Hz), 7.87 d (1H, =CH,
C6H3, J 8.7 Hz), 7.94 s (1H, =CH, C6H2), 7.99 s (1H,
=CH, C6H2), 8.13 d (1H, =CH, C6H3, J 2.0 Hz). 13C
NMR spectrum, δ, ppm: 58.2 [N(CH2CH2)2O], 61.3
[О(CH2)2], 65.9 [N(CH2)2], 119.8, 121.6 (CH), 122.6
(CH), 129.2 (CH), 129.5 (2CH), 131.2, 131.3, 131.9,
133.9. Found, %: C 48.51; H 4.11; Br 39.65; N 3.35.
C16H17Br2NО. Calculated, %: C 48.12; H 4.26; Br
40.10; N 3.51.
2,2-Dipropyl-6-bromobenzo[f]isoindolinium
bromide (3c). Yield 1.08 g (87%), white crystals, mp
175°C (anhydrous EtOH). IR spectrum, ν, cm–1: 3050,
1600 (aromatic ring), 880, 805 (1,2,4- and penta-
1
substituted benzene ring). Н NMR spectrum, δ, ppm:
0.97 t (6Н, CH3, J 7.2 Hz), 1.67–1.80 m (4Н,
CH2CH3), 3.57–3.65 m (4Н, CH2CH2CH3), 5.20 s (2H,
NCH2), 5.22 s (2H, NCH2), 7.57 d.d (1H, =CH, C6H3,
J 8.6, 2.0 Hz), 7.86 d (1H, =CH, C6H3, J 8.6 Hz), 7.88
s (1H, =CH, C6H2), 7.93 s (1H, =CH C6H2), 8.12 d
(1H, =CH, C6H3, J 2.0 Hz). 13C NMR spectrum, δ,
ppm: 10.3 (2C, CH3), 16.5 (2C, CH2CH3), 62.6 (2C,
CH2CH2CH3), 66.2 (2C, NCH2), 119.7, 120.6 (CH),
121.5 (CH), 129.1 (CH), 129.5 (2CH), 131.3, 132.4,
133.1, 133.9. Found, %: C 51.95; H 5.74; Br 39.11; N
3.21. C18H23Br2N. Calculated, %: C 52.30; H 5.57; Br
38.74; N 3.39.
REFERENCES
1. Chukhadzhyan, É.O., Chem. Heterocycl. Compd., 1993,
vol. 29, p. 363. doi 10.1007/BF00529871
2. Chukhajian, E.O., Shahkhatuni, K.G., and Chukha-
jian, El.O., Chem. Sustainable Develop., 2013, vol. 21,
p. 263.
3. Chukhajian, E.O., Nalbandyan, M.K., Gevorkyan, H.R.,
Chukhajian, El.O., Panosyan, H.A., Ayvazyan, A.G.,
and Tamazyan, R.A., J. Heterocycl. Chem., 2008, p. 687.
4. Babayan, A.T., Chukhadzhyan, E.O., and Manazyan, L.A.,
Arm. Khim. Zh., 1978, vol. 31, p. 489.
5. Babayan, A.T., Chukhadzhyan, E.O., and Babayan, G.T.,
2,2-Pentamethylene-6-bromobenzo[f]isoindol-
inium bromide (3d). Yield 1.14 g (96%), white
crystals, mp 240°C (EtOH). IR spectrum, ν, cm–1:
3080, 1580 (aromatic ring), 890, 805 (1,2,4- and penta-
Zh. Org. Khim., 1970, vol. 6, p. 1161.
6. Chukhadzhyan, E.O., Gevorkyan, A.R., Chukhad-
zhyan, El.O., and Kinoyan, F.S., Russ. J. Org. Chem.,
2005, vol. 41, p. 358. doi 10.1007/s11178-005-0170-6
1
substituted benzene ring). Н NMR spectrum, δ, ppm:
1.74–1.83 m (2Н, CH2), 1.95–2.03 m (4Н, 2CH2), 3.74
–3.79 m [4Н, N(CH2)2], 5.19 s (2H, NCH2), 5.21 s
(2H, NCH2), 7.58 d.d (1H, =CH, C6H3, J 8.7, 2.0 Hz),
7.87 d (1H, =CH, C6H3, J 8.7 Hz), 7.93 s (1H, =CH,
C6H2), 7.97 s (1H, =CH, C6H2), 8.13 d (1H, =CH,
C6H3, J 2.0 Hz). 13C NMR spectrum, δ, ppm: 20.4
(CH2), 20.8 (2CH2), 59.2 [N(CH2)2], 65.7 [N(CH2)2],
119.8, 121.5 (CH), 122.5 (CH), 129.2 (CH), 129.5
(2CH), 131.2, 131.6, 132.3, 133.9. Found, %: C 51.72;
H 4.64; Br 39.99; N 3.73. C17H19Br2N. Calculated, %:
C 51.38; H 4.79; Br 40.30; N 3.53.
7. Chukhadzhyan. E.O., Nalbandyan, M.K., Gevorkyan, A.R.,
and Kinoyan, F.S., Arm. Khim. Zh., 2007, vol. 60, p. 83.
8. Chukhadzhyan, E.O., Gevorkyan, A.R., Khachatryan, A.A.,
Chukhadzhyan, El.O., and Panosyan, G.A., Chem.
Heterocycl. Compd., 2006, vol. 42, p. 1151. doi
10.1007/s10593-006-0219-7
9. Chukhajian, E.O., Nalbandyan, M.K., Gevorkyan, A.R.,
Shakhatuni, K.G., and Panosyan, G.A., Chem.
Heterocycl. Compd., 2008, vol. 44, p. 671. doi 10.1007/
s10593-008-0090-9
10. Abramyan-Babayan, I.A. and Babayan, A.T., Arm.
Khim. Zh., 1972, vol. 25, p. 19.
11. Babayan, A.T., Atomyan, A.V., Abramyan, I.A.,
Kislina, I.S., and Vinnik, M.I., Arm. Khim. Zh., 1975,
vol. 28, p. 965.
6-bromo-1,3-dihydrospiro(benzo[f]isoindol-2,4'-
morpholin)-2-ium bromide (3e). A mixture of 3 mmol
of salt 2e, 3.5 mL of water, and 2 mL of ethanol was
stirred for 3–5 min at 65°С till it was homogeneous,
cooled to 40°С, and 0.2 mL of 3 N solution of KОН was
added (molar ratio salt–basis 5 : 1). During 2–3 min
the temperature of the reaction mixture raised to 75–
80°С. The precipitate formed after 10–15 min was
filtered off. Yield 1.17 g (97%), white crystals, mp 258–
12. Chukhajian, E.O., Khachatryan, A.A., Gevorkyan, A.R.,
and Panosyan, G.A., Chem. Heterocycl. Compd., 2007,
vol. 43, p. 701. doi 10.1007/s10593-007-0114-x
13. Dufraisse, C. and Dequesnes, A., Bull. Soc. Chim. Fr.,
1931, vol. 49, p. 1880.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 8 2018