Base-catalyzed intramolecular Diels-Alder cyclization of dialkyl(3-arylprop-2-yn-1-yl)-(3-phenylprop-2-en-1-yl)ammonium bromides in aqueous solution

Article abstract of DOI:10.1007/s10593-013-1375-1

Dialkyl(3-arylprop-2-yn-1-yl)(3-phenylprop-2-en-1-yl)ammonium bromides, in contrast to their allyl analogs containing a 3-arylprop-2-en-1-yl group, undergo cyclization in aqueous solution in the presence of base upon prior heating to give potentially biologically active 2,2-dialkyl-6-chloro-4-phenyl-3a,4- dihydrobenzo[f]isoindolinium bromides in almost quantitative yield. Heat is released in the course of these reactions. We found that the introduction of a phenyl group at position 3 of the allyl fragment facilitates the cyclization. This is the first report of a base-catalyzed intramolecular cyclization of allyl analogs of dialkyl(3-arylprop-2-yn-1-yl)ammonium salts.

Full text of DOI:10.1007/s10593-013-1375-1

Chemistry of Heterocyclic Compounds, Vol. 49, No. 9, December, 2013 (Russian Original Vol. 49, No. 9, September, 2013)
BASE-CATALYZED INTRAMOLECULAR DIELS–ALDER
CYCLIZATION OF DIALKYL(3-ARYLPROP-2-YN-1-YL)-
(3-PHENYLPROP-2-EN-1-YL)AMMONIUM BROMIDES
IN AQUEOUS SOLUTION
E. O. Chukhajian1, L. V. Ayrapetyan1*, El. O. Chukhajian1, and H. A. Panosyan1
Dialkyl(3-arylprop-2-yn-1-yl)(3-phenylprop-2-en-1-yl)ammonium bromides, in contrast to their allyl
analogs containing a 3-arylprop-2-en-1-yl group, undergo cyclization in aqueous solution in the
presence of base upon prior heating to give potentially biologically active 2,2-dialkyl-6-chloro-
4-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides in almost quantitative yield. Heat is released in
the course of these reactions. We found that the introduction of a phenyl group at position 3 of the allyl
fragment facilitates the cyclization. This is the first report of a base-catalyzed intramolecular
cyclization of allyl analogs of dialkyl(3-arylprop-2-yn-1-yl)ammonium salts.
Keywords: dialkyl(3-arylprop-2-yn-1-yl)(3-phenylprop-2-en-1-yl)ammonium bromides, 2,2-dialkyl-
6-chloro-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides, base-catalyzed intramolecular cyclization.
In 1963, Iwai and Hiraoka [1] studied the reaction of dimethylbis(3-phenylprop-2-yn-1-yl)ammonium
bromide with sodium ethylate in absolute ethanol as well as with aqueous sodium hydroxide. According to their
report 2-methyl-4-phenylbenzo[f]isoindoline should have been formed according to a scheme below that would
involve nucleophilic substitution of a methyl group and cyclization.
Ph
EtO–
+
N
Me
H
N Me
N Me
EtOH
Me
Br–
Ph
Ph
Despite these expectations, an amine product was not formed, suggesting to the authors that the second
phenyl group at position 3 of the propargyl fragment creates steric hindrance in comparison to a hydrogen atom
for the cyclization of this salt [1]. In our previous work [2], we showed that dialkyl-bis(3-phenylprop-2-yn-
1-yl)ammonium bromides undergo cyclization upon heating in aqueous solution even in the absence of base.
_______
*To whom correspondence should be addressed, e-mail: shhl@mail.ru.
1Scientific and Technological Center of Organic and Pharmacological Chemistry of National Academy of
Sciences of the Republic of Armenia, 26 Azatutyan Ave., Yerevan 0014, Armenia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1367-1374, September, 2013.
Original article submitted April 16, 2013.
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0009-3122/13/4909-1274©2013 Springer Science+Business Media New York

These findings indicate that a second phenyl group facilitates cyclization. Based on this, we suggested that a
second phenyl group at position 3 of the allyl fragment in 3-phenylprop-2-yn-1-yl salts should also facilitate
cyclization. In order to check this hypothesis, we studied the behavior of dialkyl(3-phenylprop-2-en-1-yl)-
(3-phenylprop-2-yn-1-yl)ammonium bromides under base catalysis conditions. Contrary to our expectations, the
cyclization of these salts required rather rigorous conditions [3] than for the cyclization of their allyl analogs
[4-7]. Due to poor solubility of these salts in water, the cyclization was carried out in aqueous ethanol. It is not
clear whether the reason for the usage of more rigorous conditions for this cyclization lies in use of aqueous
ethanol as the solvent or is a consequence of the second phenyl group at position 3 of the allyl group. In order to
solve this problem, we carried out the cyclization of dialkyl(3-phenylprop-2-en-1-yl)(3-phenyl-2-yn-
1-yl)ammonium bromides 1a-e and [3-(4-chlorophenyl)prop-2-yn-1-yl] analogs 1f-h under conditions
analogous to the cyclization of dimethylbis(3-phenylpropyn-2-yl)ammonium bromides [2], i.e., the mixture
consisting of the salt, water, and 2 N aqueous KOH (the salt:alkali molar ratio was 5:1) was heated at 40-50°C
for 5-6 min. Under these conditions, the starting salt completely dissolves and cyclization proceeds with a heat
release. The temperature of the reaction mixture rises to 75-80°C. In the case of salts 1f,g the temperature of the
reaction mixture rises only to 55-60°C, and additional heating of the reaction mixture at 70-72°C for 15-20 min
is required for complete conversion.
Ph
Ph
Br–
Ph
Br–
H
X
4
KOH, H2O
40–50 75–80°C
5
8
X
+
+
3
1
3a
+
R2N
R2N
9
R2N
X
Br–
2a–h
OH–
1a–h
a R = Me, b,f R = Et, c R2 = (CH2)4, d,g R2 = (CH2)5, e,h R2 = (CH2)2O(CH2)2,
a–e Х = H, f–h X = Cl
Final products 2a-h are formed according to the mechanism, which we have already proposed for the
cyclization of salts, containing an allyl or propargyl group along with the 3-alkenyl or 3-arylpropagyl fragments
[8-10]. According to the proposed mechanism, the enyne fragment directly participates in the cyclization, while
the base serves as the "driving force" of the process involving electron transfer through a six-membered cyclic
mechanism.
Under these conditions, in contrast to cyclization in aqueous ethanol solution [3], we obtain only
2,2-dialkyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides 2a-e (83-92% yield) and their 6-chloro
analogs 2f-h (85-92% yield).
The formation of these compounds may be attributed to the very rapid rate of cyclization of salts 1a-h in
aqueous media under mild conditions and the inability of cyclic products 2a-h to isomerize to give derivatives
of 9-phenyl-3a,4-dihydrobenzo[f]isoindolinium salts as observed in the case of bromides 1b,d upon cyclization
in aqueous ethanol solution in the presence of 0.5 equivalent of aqueous alkali upon heating for 5-6 h [3].
1
We should note that the H and 13C NMR spectra of 2,2-dialkyl-4-phenyl-3a,4-dihydrobenzo[f]iso-
indolinium bromides and their 9-phenyl isomers [3] show characteristic differences. Thus, the methylene
1
protons at position 1 in the H NMR spectra of 4-phenyl derivatives 2a-h appear at 4.6-5.0 ppm as an AB spin
system with 2J ~ 16.0 Hz. The 13C NMR spectra of these compounds have two signals for the 3a,4-CH groups at
40.2-41.9 and 48.3-48.6 ppm. The assignment of these signals to the 3a,4-CH groups was made using the results
of DEPT and HMQC experiments. The 13C NMR spectra of the 9-aryl derivatives have a signal for only one CH
group at 35 ppm, while the other signals for sp3-carbon atoms were assigned to CH2 groups using the DEPT
experimental data [3].
In order to establish the effect of the phenyl group at position 3 of the allyl fragment on the course of
the cyclization, we carried out the reaction of dimethylallyl(3-phenylprop-2-yn-1-yl)ammonium bromide
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lacking a phenyl group under the conditions for cyclization of the 3-phenyl analogs. We added 2 N aqueous
KOH to a homogeneous solution consisting of 8 mmol salt and 1.8 ml water (the salt:alkali molar ratio was 5:1).
No heat liberation was noted upon adding the alkali solution. The reaction course was followed by IR
spectroscopy, occasionally taking probes of the reaction mixture. The probes were washed with ether to remove
possible side products, and the spectra were recorded in a water-resistant calcium fluoride cell. We should note
that we initially recorded the IR spectra of an aqueous solution of the starting salt without added alkali. The
intensity of the absorption band at 2200-2220 cm-1 for the doubly-substituted acetylenic bond remained
unchanged even upon prolonged standing at room temperature (probes were taken three times every 24 h).
Then, KOH (0.1 g, 1.8 mmol) was added to the reaction mixture, which was then heated at 85-87°C for 2.5 h.
A probe was taken for recording the IR spectrum. Under these conditions, the absorption characteristic for the
doubly-substituted acetylenic bond had already disappeared. A precipitate of 2,2-dimethyl-3a,4-dihydro-
benzo[f]isoindolinium bromide formed after maintenance of the reaction mixture for 20-25 min at room
temperature. The melting point of the precipitate was 243-245°C. The melting point of a mixed sample of this
precipitate and an authentic sample of the indicated salt was undepressed [4]. Thus, we conclude that the IR
spectral data and the relative capacities of the allyl salts to undergo cyclization [4-7] suggest that the phenyl
group at position 3 of the allyl fragment facilitates the cyclization analogously to 3-phenylpropargyl salts [2].
This result is the only case of a base-catalyzed cyclization of ammonium salts containing a 3-arylprop-
2-yn-1-yl group along with an allyl group [4-7].
We should note that bromides 2a,e obtained in aqueous ethanol [3] and aqueous solutions have the same
1
structure as indicated by H NMR spectroscopy but different melting points. Analogous studies by Laird and
Ollis [11, 12] appeared after publication of our investigation of the cyclization of dialkyl(allyl)(3-aryl-
propargyl)ammonium bromides [4]. These authors also studied the base-catalyzed cyclization of dimethyl-
(3-phenylprop-2-en-1-yl)(3-phenylprop-2-yn-1-yl)ammonium bromide (1a) under conditions analogous to the
conditions for the cyclization of dimethylbis(3-phenylprop-2-yn-1-yl)- [2] and dimethyl(propargyl)(3-phenyl-
prop-2-yn-1-yl)ammonium bromides [13, 14]. Cyclization at room temperature gave 2,2-dimethyl-4-phenyl-
3a,4-dihydrobenzo[f]isoindolinium bromide (2a) in 56% yield. The structure of bromide 2a was supported by
1H NMR spectroscopy. The melting point of bromide salt 2a given by these authors (158-160°C) does not
correspond to the melting point of 2,2-dimethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromide (2a),
which we obtained in the cyclization of dimethyl(3-phenylprop-2-en-1-yl)(3-phenylprop-2-yn-1-yl)ammonium
bromide both in aqueous ethanol solution [3] and in water. After neutralization of the mother liquor by adding
48% hydrobromic acid and evaporation, these authors isolated the remaining fraction of the salt (44% yield) but
neither the melting point nor spectral data were given for the isolated salt.
Our studies have applied significance as well as importance for basic research; in contrast to the results
of previous investigation [3], potentially biologically active 2,2-dialkyl-4-phenyl-3a,4-dihydro-
benzo[f]isoindolinium bromides 2a-e and their 6-chloro analogs 2f-h were isolated after 30 min in almost
quantitative yield. These salts had been difficult to obtain by other methods.
2,2-Dialkyl-3a,4-dihydroisoindolinium and 2,2-dialkyl-3a,4-dihydrobenzo[f]isoindolinium bromides
have pronounced hypertensive action and stimulate respiration. Their condensed analogs, synthesized in our
previous work [15] have hypotensive and non-narcotic analgesic activity as well as anticoagulation activity,
were protected by USSR Inventor's Certificates [16-24] and Republic of Armenia patents [25, 26].
The structures of the starting bromides (in particular, bromides 1f-h, which are reported for the first
1
time) and cyclic salts 2a-h were demonstrated by IR, H NMR, and 13C NMR spectroscopy data. Double
resonance and two-dimensional COSY, NOESY, DEPT, and HMQC spectroscopy were used to confirm the
structure of salts 2a-h.
Thus, the cyclization of dialkyl(3-arylprop-2-yn-1-yl)(3-phenylprop-2-en-1-yl)ammonium bromide in
aqueous solution upon brief heating in the presence of alkali gives potentially biologically active 2,2-dialkyl-
4-phenyl-6-3a,4-dihydrobenzo[f]isoindolinium bromides in almost quantitative yield. These results differ from
the data for previous attempts to cyclize analogous salts in aqueous ethanol solution, in which 9-phenyl isomers
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were obtained under more rigorous conditions. It was also shown that the introduction of a phenyl group at
position 3 of the allyl fragment facilitates cyclization.
EXPERIMENTAL
1
13
The IR spectra were recorded on a Specord 75 IR spectrometer in chloroform. The H and C NMR
spectra were recorded on a Varian Mercury 300 VX spectrometer (300 and 75 MHz, respectively) in DMSO-d6–
CCl4 (1:3) with TMS as internal standard. The elemental analysis for C, H, and N was carried out on a compact
Vario MICRO cube. The analysis for bromide anions was carried out by the method of Abramyan and Sargsyan
[27]. The melting points were determined on an instrument manufactured by VEB Wägetechnik Rapido
Radebeul Betrieb of the VEB Kombinat NAGEMA in the German Democratic Republic. The purity of the
cyclic salts was monitored by thin-layer chromatography on Silufol UV-254 plates with 10:2:1:5 n-BuOH–
EtOH–H2O–AcOH as the eluent. Iodine vapor was used for visualization.
Starting dialkyl(3-phenylprop-2-yn-1-yl)- and dialkyl[3-(4-chlorophenyl)prop-2-yn-1-yl)amines were
obtained according to our previous procedures [28, 29, 30]. Starting salts 1a-e were prepared according to our
reported procedure [3].
Synthesis of Bromides 1f-h (General Method). Phenylallyl bromide [31] (4.33 g, 22 mmol) was added
to a solution of the corresponding N-[3-(4-chlorophenyl)prop-2-yn-1-yl]amine in ether (10 ml) and acetonitrile
(4 ml), and the mixture was left at room temperature overnight to give a precipitate of salt 1f-h.
Diethyl[3-(4-chlorophenyl)prop-2-yn-1-yl](3-phenylprop-2-en-1-yl)ammonium Bromide (1f). Yield
5.8 g (93%), white hygroscopic crystals, mp 85-87°С. IR spectrum, ν, cm-1: 3050, 3010 (Ar), 2220 (С≡С), 1630
(–СН=СН–), 1600, 1580, 810 (Ar), 780, 720, 680 (Ph). 1Н NMR spectrum, δ, ppm (J, Hz): 7.61-7.54 (5Н, m, H
Ar); 7.39-7.25 (4Н, m, H Ar), 7.09 (1Н, d, J = 15.6, PhСН=); 6.53 (1Н, dt, J = 15.6, J = 7.3, =СНСН2); 4.77
(2Н, s, C≡CСН2); 4.37 (2Н, d, J = 7.3, =CHСН2); 3.63 (4H, q, J = 7.1, 2CH2СН3); 1.45 (6H, t, J = 7.1,
2CH2CH3). Found, %: С 63.54; Н 6.18; Br 19.54; N 3.28. C22H25BrClN. Calculated, %: С 63.09; Н 6.02;
Br 19.08; N 3.34.
[3-(4-Chlorophenyl)prop-2-yn-1-yl](3-phenylprop-2-en-1-yl)piperidinium Bromide (1g). Yield 6.1 g
(95%), shiny white crystals, mp 170-172°С. IR spectrum, ν, cm-1: 3010 (Ar), 2240 (С≡С), 1630 (–СН=СН–),
1
1600, 1580, 840, 810 (Ar), 710, 700, 680 (Ph). Н NMR spectrum, δ, ppm (J, Hz): 7.60-7.56 (4Н, m, H Ar);
7.40-7.25 (5Н, m, H Ar); 7.08 (1Н, d, J = 15.6, PhСН=); 6.54 (1Н, dt, J = 15.6, J = 7.4, =СНСН2); 4.86 (2Н, s,
С≡ССН2); 4.51 (2Н, d, J = 7.4, =CHСН2); 3.79-3.72 (4H, m, 2,6-CH2 piperidine); 2.08-1.92 (4H, m, 3,5-CH2
piperidine); 1.80-1.70 (2H, m, 4-CH2 piperidine). Found, %: С 64.58; Н 6.01; Br 18.97; N 3.42. C23H25BrClN.
Calculated, %: С 64.12; Н 5.85; Br 18.55; N 3.25.
[3-(4-Chlorophenyl)prop-2-yn-1-yl](3-phenylprop-2-en-1-yl)morpholinium Bromide (1h). Yield
5.6 g (87%), white crystals, mp 153-155°С (abs. EtOH). IR spectrum, ν, cm-1: 3060, 3010 (Ar), 2220 (С≡С),
1630 (–CH=CH–), 1600, 1580, 840, 810 (Ar), 720, 700, 680 (Ph). 1Н NMR spectrum, δ, ppm (J, Hz): 7.62-7.57
(4Н, m, H Ar); 7.40-7.28 (5H, m, H Ar); 7.12 (1Н, d, J = 15.7, PhСН=); 6.57 (1Н, dt, J = 15.7, J = 7.5,
=CHСН2); 5.03 (2Н, s, С≡ССН2); 4.67 (2Н, d, J = 7.5, =СНСН2); 4.19-4.02 (4H, m, N(CH2CH2)2O); 3.85-3.76
(4H, m, N(CH2CH2)2O). 13С NMR spectrum, δ, ppm: 141.7; 135.0; 134.7 (=СH); 133.3; 128.3 (CH); 128.2
(2СН); 128.0 (2СН); 127.1 (2СН); 119.0 (2СН); 114.9 (CH); 89.7, 77.9 (С≡С); 61.2 (NСН2); 59.6
(N(CH2CH2)2O); 56.2 (N(CH2CH2)2O); 50.1 (CH2). Found, %: С 60.58; Н 5.12; Вr 18.93; N 3.45.
C22H23ВrClNО. Calculated, %: С 61.06; Н 5.36; Вr 18.46; N 3.24.
Intramolecular Cyclization of Bromides 1a-h (General Method). A mixture consisting of salt 1a-h
(2.8 mmol), water (1-2 ml), and 2 N aqueous KOH solution (0.28 ml) (the salt:KOH molar ratio was 5:1) was
heated on a warm water bath for 5-6 min. The salt completely dissolved at 40-50°C. Heat generation rapidly
ensued, and the temperature of the reaction mixture rose to 75-80°C. In the case of salts 1g,h, the temperature
rose only to 55-60°C and the mixture was heated at 70-72°C for 15-20 min to insure complete conversion. After
1277

maintenance at room temperature for 1.0-1.5 h, the mixture was extracted with ether (2×15 ml) to remove
possible side products. Filtration of the reaction mixture gave cyclic salts 2a-h, which were then recrystallized
from water or absolute ethanol.
2,2-Dimethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2a). Yield 0.87 g (87%), shiny
white crystals, mp 245-247°С (Н2О). IR spectrum, ν, cm-1: 3060, 3020, 3000, 1940 (Ar), 1630 (C=CH), 1600,
1580, 770, 740, 700, 670 (Ar). 1Н NMR spectrum, δ, ppm (J, Hz): 7.46-7.31 (5Н, m, H Ph); 7.21-7.13 (2Н, m,
H Ar); 7.04 (1Н, td, J = 7.2, J = 2.2, H Ar); 6.73-6.70 (1Н, m, H-9); 6.54 (1Н, br. d, J = 7.6, H Ar); 4.78-4.64
(2Н, m, 1-CH2); 4.21 (1H, d, J = 14.0, 4-CH); 3.88-3.61 (3Н, m, 3-СН2, 3а-СН); 3.43 (3Н, s, СН3); 3.25 (3Н, s,
СН3). 13С NMR spectrum, δ, ppm: 139.8; 137.2; 135.5; 133.5 (=С); 128.4; 128.4; 127.0; 126.8; 126.4; 126.3;
126.1; 121.2 (=СН); 68.0, 67.4 (1,3-СН2); 51.9 (NСН3); 51.4 (NСН3); 48.6 (4-СН); 41.9 (3a-СН). Found, %:
С 66.95; Н 5.97; Br 22.91; N 4.14. C20H22BrN. Calculated, %: С 67.42; Н 6.22; Br 22.43; N 3.93.
2,2-Diethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2b). Yield 0.9 g (83%), shiny
white crystals, mp 127-130°С (Н2О). IR spectrum, ν, cm-1: 3060, 3020, 3000 (Ar), 1940 (Ph), 1640 (C=CH),
1
1610, 1570 (Ar), 770, 740, 710, 680 (Ph). Н NMR spectrum, δ, ppm (J, Hz): 7.45-7.30 (5Н, m, H Ph);
7.21-7.12 (2Н, m, H Ar); 7.02 (1Н, td, J = 7.5, J = 2.0, H Ar); 6.71 (1Н, q, J = 2.3, Н-9); 6.50 (1Н, br. d, J = 7.5,
H Ar); 4.67 (2Н, br. s, 1-СН2); 4.23 (1Н, d, J = 14.3, 4-СН); 3.82-3.37 (7Н, m, 3-CH2, 3a-CH, 2CH2СН3); 1.33
(3Н, t, J = 7.1, CH2СН3); 1.26 (3Н, t, J = 7.1, CH2СН3). 13С NMR spectrum, δ, ppm: 139.9; 137.4; 135.1; 133.5
(=С); 128.6 (2С); 127.1; 126.9; 126.5; 126.4; 126.2; 121.3 (=СН); 64.3, 64.2 (1,3-СН2); 54.9 (NСН2СН3); 53.4
(NСН2СН3); 48.6 (4-СН); 41.3 (3a-СН); 8.5 (NСН2СН3); 8.2 (NСН2СН3). Found, %: С 69.22; Br 21.23;
Н 6.99; N 3.85. C22H26BrN. Calculated, %: С 68.75; Н 6.82; Br 20.79; N 3.64.
4-Phenyl-2,2-tetramethylene-3a,4-dihydrobenzo[f]isoindolinium Bromide (2c). Yield 0.9 g (83%).
The sample of salt 2c obtained by the method described above did not give a depressed melting point in a mixed
sample with an authentic sample [3].
2,2-Pentamethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2d). Yield 1.0 g (90%),
white crystals, mp 170-172°С (Н2О). IR spectrum, ν, cm-1: 3060, 3030, 3010 (Ar), 1940 (Ph), 1630 (C=CH),
1
1610, 1580 (Ar), 780, 760, 720, 690 (Ph). Н NMR spectrum, δ, ppm (J, Hz): 7.46-7.32 (5Н, m, H Ph);
7.23-7.11 (2Н, m, H Ar); 7.03 (1Н, ddd, J = 7.7, J = 6.9, J = 2.0, Н Ar); 6.72 (1Н, q, J = 2.0, H-9); 6.51 (1Н, br.
d, J = 7.7, H Ar); 4.81 (1Н, br. d, J = 16.0, 1-СН2); 4.69 (1Н, br. d, J = 16.0, 1-СН2); 4.21 (1Н, dt, J = 14.3,
J = 6.4, Н-3а); 3.87-3.45 (7Н, m, 3-СН2, 4-СН, 2,6-СН2 piperidine); 2.00-1.55 (6Н, m, 3,4,5-СН2 piperidine).
13С NMR spectrum, δ, ppm: 139.8; 137.3; 134.9; 133.4 (=С); 128.5 (2С); 127.0; 126.9; 126.4; 126.3; 126.1;
121.4 (=СН); 65.1, 63.6 (1,3-СН2); 60.5, 58.9 (2,6-СН2 piperidine); 48.7 (4-СН); 40.8 (3а-СН); 20.9, 20.5, 20.4
(3,4,5-СН2 piperidine). Found, %: С 70.16; Н 6.78; Br 20.64; N 3.75. C23H26BrN. Calculated, %: С 69.70;
Н 6.61; Br 20.16; N 3.53.
4-Phenylspiro-3a,4-dihydrobenzo[f]isoindoline-2,4'-morpholinium Bromide (2e). Yield 1.0 g
(92%), shiny crystals, mp 210-213°С (abs. EtOH). IR spectrum, ν, cm-1: 3060, 3020, 3010 (Ar), 1940 (Ph),
1630 (C=CH), 1620, 1590 (Ar), 770, 760, 720, 680 (Ph). 1Н NMR spectrum, δ, ppm (J, Hz): 7.46-7.31 (5Н, m,
H Ph); 7.25-7.11 (2Н, m, H Ar); 7.03 (1Н, td, J = 7.5, J = 1.7, Н Ar); 6.73 (1Н, br. q, J = 2.3, Н-9); 6.52 (1Н,
br. d, J = 7.5, H Ar); 5.04 (1Н, dd, J = 16.0, J = 1.5) and 4.85 (1Н, dt, J = 16.0, J = 2.1, 1-СН2); 4.25 (1Н, d,
13
J = 14.4, 4-CH); 4.07-3.71 (9Н, m) and 3.66-3.58 (2Н, m, 3-CH2, 3a-CH, N(CH2CH2)2O). С NMR spectrum,
δ, ppm: 139.5; 138.9; 135.2; 132.3; 132.1 (=С); 128.7; 127.4; 127.2 (3С, =СН); 126.4; 120.4 (3С); 66.2, 63.5
(1,3-СН2); 61.4, 61.0 (N(CH2CH2)2O); 59.4, 58.1 (N(CH2CH2)2O); 48.3 (4-СН); 40.2 (3a-СН). Found, %:
С 65.86; Н 5.83; Br 20.55; N 3.73. C22H24BrNО. Calculated, %: С 66.34; Н 6.07; Br 20.06; N 3.52.
6-Chloro-2,2-diethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2f). Yield 1.0 g (86%),
white crystals, mp 165-167°С (Н2О). IR spectrum, ν, cm-1: 1940 (Ph), 1620 (С=СН), 1580 (Ar), 870 (Ph), 805
(Ar), 770, 730, 710, 690 (Ph). 1Н NMR spectrum , δ, ppm (J, Hz): 7.48-7.34 (5Н, m, H Ph); 7.25-7.14 (2Н, m,
H Ar); 6.72 (1Н, br. s, Н-9); 6.41 (1Н, br. s, H Ar); 4.72 (2Н, s, 1-СН2); 4.31 (1Н, d, J = 14.3, 4-CH); 3.86-3.38
(7Н, m, 3-CH2, 3a-CH, N(CH2CH3)2); 1.33 (3Н, t, J = 7.1) and 1.27 (3Н, t, J = 7.1, N(CH2CH3)2). Found, %:
С 63.56; Н 6.17; Br 19.56; N 3.56. C22H25BrClN. Calculated, %: С 63.09; Н 6.02; Br 19.08; N 3.34.
1278

6-Chloro-2,2-pentamethylene-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2g). Yield
1.0 g (85%), white crystals, mp 158-160°С (EtOH–H2O). IR spectrum, ν, cm-1: 1940, 1620 (C=CH), 1580, 3010
(Ar), 870 (Ph), 805, 820 (Ar), 690, 710, 730, 770. 1Н NMR spectrum, δ, ppm (J, Hz): 7.49-7.34 (5Н, m, H Ph);
7.21 (1Н, d, J = 8.1, Н Ar); 7.15 (1Н, ddd, J = 8.1, J = 2.0, J = 0.8, Н Ar); 6.72 (1Н, br. s, Н-9); 6.42 (1Н, br. s,
Н Ar); 4.84 (1Н, br. d, J = 16.1) and 4.71 (1Н, br. d, J = 16.1, 1-СН2); 4.27 (1Н, d, J = 13.4, 4-СН); 3.91-3.41
(7H, m, 3-СH2, 3a-CH, 2,6-СН2 piperidine); 2.00-1.54 (6H, m, 3,4,5-СН2 piperidine). 13С NMR spectrum, δ,
ppm: 139.6; 138.9; 135.6; 132.2; 132.1 (=С); 128.7; 128.5 (br. s); 127.4; 127.2 (=CH); 126.3 (С-2,3,5,6 Ph);
126.2 (br. s); 120.3 (CH); 65.3, 63.6 (1,3-СН2); 60.5, 58.7 (2,6-СН2 piperidine); 48.3 (4-СН); 40.4 (3a-СН);
20.9, 20.4, 20.3 (3,4,5-СН2 piperidine). Found, %: С 63.65; Н 5.59; Br 18.29; N 3.46. C23H25BrClN. Calculated,
%: С 64.12; Н 5.85; Br 18.55; N 3.25.
6-Chloro-4-phenyl-3a,4-dihydrobenzo[f]isoindoline-2,4'-mopholinium Bromide (2h). Yield 1.1 g
(92%), shiny white crystals, mp 170-172°С (Н2О). IR spectrum, ν, cm-1: 1940 (Ph), 1640 (С=СН), 1600, 1590,
1
1520 (Ar), 870 (Ph), 810 (Ar), 780, 720, 700, 680 (Ph). Н NMR spectrum, δ, ppm (J, Hz): 7.50-7.34 (5Н, m,
H Ph); 7.22 (1Н, d, J = 8.1, H Ar); 7.16 (1Н, dd, J = 8.1, J = 2.1, H Ar); 6.73 (1Н, br. s, Н-9); 6.41 (1Н, d,
J = 2.1, H Ar); 5.04 (1Н, br. d, J = 16.0) and 4.85 (1Н, br. d, J = 16.0, 1-СН2); 4.28 (1Н, d, J = 14.5, 4-СН);
4.07-3.71 (9Н, m) and 3.66-3.57 (2Н, m, 3-CH2, 3a-СН, N(CH2CH2)2O). 13С NMR spectrum, δ, ppm: 139.5
(=С); 138.9; 135.2; 132.3; 132.1 (=С); 128.7; 128.7 (br. s); 127.4; 127.2; 127.2 (br. s); 126.4 (=СН); 126.4;
66.2, 63.5 (1,3-СН2); 61.4, 61.0 (N(CH2CH2)2O); 59.4, 58.1 (N(CH2CH2)2O); 48.3 (4-СН); 40.2 (3a-СН).
Found, %: С 61.51; Н 5.55; Br 18.98; N 3.46. C22H23BrClNО. Calculated, %: С 61.06; Н 5.36; Br 18.46;
N 3.24.
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