Cyclization of dialkyl(3-phenylpropen-2-yl)-(3-phenylpropyn-2-l)ammonium bromides by the action of an aqueous alkali solution. aqueous-alkaline cleavage of the cyclization products - N,n-dialkyl-4(9)-phenyl-3a,4-dihydro-benzo[f] isoindolinium bromides

Article abstract of DOI:10.1007/s10593-012-1138-4

When heated in an alkaline aqueous medium, dialkyl(3-phenylpropen-2-yl)(3- phenylpropyn-2-yl)- ammonium bromides undergo intramolecular cyclization, forming N,N-dialkyl-4(9)-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides. The cyclization products undergo aqueous-alkaline cleavage at the C(1)-N(2) or N(2)-C(3) bond, which leads to a mixture of 2-(dialkylaminomethyl)-3-methyl- and 3-(dialkylaminomethyl)-2-methyl-1-phenylnaphthalenes. However, only the C(1)-N(2) bond cleavage product is formed in the case of 2,2-pentamethylene-9- phenyl-3a,4-dihydrobenzo-[f]isoindolinium bromide.

Full text of DOI:10.1007/s10593-012-1138-4

Chemistry of Heterocyclic Compounds, Vol. 48, No. 9, December, 2012 (Russian Original Vol. 48, No. 9, September, 2012)
CYCLIZATION OF DIALKYL(3-PHENYLPROPEN-2-YL)-
(3-PHENYLPROPYN-2-YL)AMMONIUM BROMIDES BY
THE ACTION OF AN AQUEOUS ALKALI SOLUTION.
AQUEOUS-ALKALINE CLEAVAGE OF THE CYCLIZATION
PRODUCTS – N,N-DIALKYL-4(9)-PHENYL-3a,4-DIHYDRO-
BENZO[f]ISOINDOLINIUM BROMIDES
E. O. Chukhajian1, L. V. Ayrapetyan1, El. O. Chukhajian1, and H. A. Panosyan1*
When heated in an alkaline aqueous medium, dialkyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)-
ammonium bromides undergo intramolecular cyclization, forming N,N-dialkyl-4(9)-phenyl-
3a,4-dihydrobenzo[f]isoindolinium bromides. The cyclization products undergo aqueous-alkaline
cleavage at the C(1)–N(2) or N(2)–C(3) bond, which leads to a mixture of 2-(dialkylaminomethyl)-
3-methyl- and 3-(dialkylaminomethyl)-2-methyl-1-phenylnaphthalenes. However, only the C(1)–N(2)
bond cleavage product is formed in the case of 2,2-pentamethylene-9-phenyl-3a,4-dihydrobenzo-
[f]isoindolinium bromide.
Keywords: (dialkylaminomethyl)naphthalenes, dialkyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)ammo-
nium bromides, isoindolinium salts, aqueous-alkaline cleavage, intramolecular cyclization.
Earlier in papers by A. T. Babayan and co-workers it was established that under conditions of base
catalysis at room temperature ammonium salts with the general formula Alk2(HС≡CCH2)(ArC≡CCH2)N+X–
(X = Hal; Ar = Ph, 4-MeC6H4, 4-ClC6H4) undergo intramolecular cyclization with spontaneous heating [1-4].
The cyclization of similar salts with an allyl fragment in place of the propargyl fragment under conditions of
base catalysis occurs on heating (2-3 h, 90-92°C) [2, 3, 5, 6].
After the publication of investigations into the cyclization of (allyl)(3-phenylpropargyl)-substituted
ammonium salts [5], papers with similar content were also published by British scientists [7, 8]. Japanese
researchers obtained 2-methylbenzo[f]isoindoline in 22% yield from dimethyl(propargyl)(3-phenyl-
propargyl)ammonium bromide with sodium ethoxide in absolute ethanol [9]. In the same investigation the
expected 2-methyl-4-phenylbenzo[f]isoindoline was not obtained from dimethylbis(3-phenylpropargyl)-
ammonium bromide either with sodium ethoxide in absolute ethanol or with NaOH in aqueous solution, and
_______
*To whom correspondence should be addressed, e-mail: shhl@mail.ru.
1Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Sciences,
Republic of Armenia, 26 Azatutyan Ave., Yerevan 0014, Republic of Armenia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1410-1417, September, 2012.
Original article submitted February 20, 2011; revision submitted January 31, 2012.
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0009-3122/12/4809-1314©2012 Springer Science+Business Media New York

the authors explained this by steric effects. A. T. Babayan and co-workers established that the
Alk2(PhC≡CCH2)2N+X– salts undergo cyclization when their aqueous solutions are heated even in the absence
of bases, i.e., the cyclization is apparently facilitated by the second phenyl group [10].
Based on those considerations we assumed that the second phenyl group, located at the γ-position of the
allyl substituent (in place of one phenylpropargyl group), must also promote cyclization. To check this
assumption in the present work, we studied the behavior of dialkyl(3-phenylpropen-2-yl)(3-phenylpropyn-
2-yl)ammonium bromides 1a-f under the conditions of base catalysis. Contrary to our expectations, the
cyclization of the salts 1a-f took place under fairly rigorous conditions (salt:alkali molar ratio 2:1, reaction time
5-6 h at 90-92°C). The salts 1a-f are poorly soluble in water, and the reaction was therefore conducted in a
water-alcohol solution. As a result of the cyclization of salts 1a-d, the corresponding dialkyl-4-phenyl-3a,4-di-
hydrobenzo[f]isoindolinium bromides 2a-d are formed in 62-72% yields.
Ph
Br–
Ph
3a
4
R
R
R1
+
N
KОН, H2O
5
8
3
+
N
9
1
R1
Ph
90–92°C
Br–
1a–d
2a–d
а R = R1 = Me, b R = R1 = Pr, c R+R1 = –(CH2)4–, d R+R1 = –(CH2)2O(CH2)2–
The bromides 1e,f under the same conditions did not produce the 4-phenyl-substituted salts 2e,f, but
rather their 9-phenyl-substituted isomers 3a,b with yields of 65-68%.
Ph
Ph
Ph
H
R
+
N
9
4
KОН, H2O
R
+
N
1
3
8
5
R
+
N
1e,f
H
R1
R1
90–92°C
R1
3a
Br–
Br–
Br–
3a,b
2e,f
1e, 2e, 3a R = R1 = Et, 1f, 2f, 3b R+R1 = –(CH2)5–
It should be noted that the product formed upon the cyclization of salt 1b under the conditions of base
catalysis could not be obtained in the crystalline state, and it was therefore used in further transformations
without isolation of the cyclic salt 2b.
Ph
Ph
R
R
1
N
I
N
R1
H
3
R1
Me
H2C
4a–d
KОН, H2O
2a–d
110–120°C
Ph
Ph
Me
H2C
1
3
II
R
R
H
N
N
R1
R1
5a–d
4,5 a R = R1 = Me, b R = R1 = Pr, c R+R1 = –(CH2)4–, d R+R1 = –(CH2)2O(CH2)2–
1315

When refluxed in a 25% KOH solution, the salts 2a-d are cleaved quite smoothly at the C(1)–N(2) bond
(path I) or N(2)–C(3) bond (path II), forming a mixture of the isomeric 2-(dialkylaminomethyl)-3-methyl-
1-phenylnaphthalenes 4a-d and 3-(dialkylaminomethyl)-2-methyl-1-phenylnaphthalenes 5a-d with overall
yields of 65-68%.
Under the same conditions, a mixture of the amines 4e and 5e was formed from the salt 3a, while only
the isomer 4f was obtained from compound 3b with a yield of 75%.
Ph
Ph
R
R
I
N
N
R1
R1
Me
H2C
4e,f
KОН, H2O
H
3a,b
110–120°C
Ph
Ph
Me
H2C
II
Et
Et
Et
Et
H
N
(from 3a)
N
5e
4 e R = R1 = Et, f R+R1 = –(CH2)5–
The presented structures of the salts 1a-f, 2a-d, 3a,b and the amines 4a-f, 5a-e agree well with their IR
1
and H NMR spectral data. The structure of the salts 2a,c,d and 3a,b was also confirmed by 13C NMR
spectroscopy. Double resonance and two-dimensional correlation spectroscopy (COSY, NOESY, DEPT,
HMQC) were used to assign the signals in the 1H and 13C NMR spectra. Thus, in the spectra of the isomers 4a-f,
a nuclear Overhauser effect is observed for the signals of the protons of the 3-CH3 group and H-4, and also for
the protons of the CH2 group and the ortho-proton of the phenyl substituent. On the other hand, the spectra of
the isomers 5a-e exhibit a nuclear Overhauser effect for the signals of the 2-CH2 group and the ortho-proton of
the phenyl substituent, and also for the signals of the CH2 group and the H-4 proton. The signals of the 2-CH2
and 3-CH2 groups and also the 2-CH3 and 3-CH3 groups have different chemical shifts, allowing to determine
fairly accurately the content of the isomers 4 and 5 from the signal intensity ratio in the reaction product spectra.
It was shown that the content of the isomer 4 in the mixtures obtained from compounds 2a-d, 3a amounts to
68-80%.
Thus, in comparison with the other allyl analogs, the cyclization of (3-phenylpropen-2-yl)-
(3-phenylpropyn-2-yl)ammonium bromides in an water-alcohol solution of alkali leads to high yields of dialkyl-
4(9)-phenyl-3a,4-dihydrobenzo[f]isoindolinium bromides. It was found that these salts undergo aqueous-
alkaline cleavage at the C(1)–N(2) and N(2)–C(3) bonds. 2,2-Pentamethylene-9-phenyl-3a,4-dihydrobenzo-
[f]isoindolinium bromide is only cleaved at the C(1)–N(2) bond.
EXPERIMENTAL
The IR spectra of the salts 1a-f, 2a,c,d, 3a,b (films from chloroform) and the amines 4a-f, 5a-e (thin
1
layers) were recorded on a Specord IR-75 spectrometer. The H and 13C NMR spectra were recorded on a
Varian Mercury 300 VX spectrometer (300 and 75 MHz, respectively) in 1:3 DMSO-d6–CCl4 with TMS as
internal standard. Elemental analysis was performed on a Vario MICRO Cube compact element analyzer. The
melting points of the salts were determined on a VEB Wägetechnik Rapido instrument. The purity of the
obtained compounds was monitored by TLC on Silufol UV-254 plates in the 10:2:1:5 n-BuOH–EtOH–H2O–
AcOH system and visualization with iodine vapor.
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Preparation of Salts 1a-f (General Method). 3-Bromo-1-phenylpropene [14] (4.2 g, 22.5 mmol) was
added to a solution of the corresponding dialkyl(3-phenylpropyn-2-yl)amine [11-13] (15.0 mmol) in Et2O (20 ml)
and MeCN (5 ml). The reaction occurred with moderate spontaneous heating. The precipitated salts 1a-f were
washed with absolute Et2O (2×30 ml). The product was recrystallized from absolute EtOH.
Dimethyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)ammonium Bromide (1a). Yield 5.2 g (97%).
White crystals, mp 130–132°С. IR spectrum, ν, cm-1: 1580, 1600, 3010, 3060 (Ar), 2240 (C≡C), 1630 (C=C),
1
1940, 730, 700, 680 (Ph). H NMR spectrum, δ, ppm (J, Hz): 7.60-7.55 (6Н, m, H Ph); 7.45-7.25 (4Н, m,
H Ph); 7.06 (1Н, d, J = 15.6, =СНРh); 6.55 (1Н, dt, J = 15.6, J = 7.5, СН2СН=); 4.87 (2Н, s, NСН2C≡C); 4.52
(2Н, d, J = 7.5, NСН2CH=); 3.37 (6Н, s, N(СН3)2). Found, %: С 67.88; Н 6.49; Br 22.77; N 4.18. C20H22BrN.
Calculated, %: С 67.42; Н 6.22; Br 22.43; N 3.93.
Dipropyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)ammonium Bromide (1b). Yield 6.0 g (97%).
White crystals, mp 170-174°С. IR spectrum, ν, cm-1: 1580, 1600, 3010, 3050 (Ph), 2240 (С≡С), 1640 (С=С),
1
1930, 720, 700, 680 (Ph). H NMR spectrum, δ, ppm (J, Hz): 7.61-7.50 (6Н, m, Н Ph); 7.45-7.25 (4Н, m,
Н Ph); 7.08 (1H, d, J = 15.6, =СНРh); 6.54 (1Н, dt, J = 15.6, J = 7.4, СН2СН=); 4.79 (2Н, s, NСН2C≡C); 4.41
(2Н, d, J = 7.4, NСН2CH=); 3.52-3.46 (4Н, m, N(СН2CH2CH3)2); 1.98-1.84 (4Н, m, N(СН2CH2CH3)2); 1.06
(6Н, t, J = 7.2, 2СН3). Found, %: С 69.43; Н 6.96; Вr 19.67; N 3.77. C24H30BrN. Calculated, %: С 69.90;
Н 7.33; Вr 19.37; N 3.40.
N-(3-Phenylpropen-2-yl)-N-(3-phenylpropyn-2-yl)pyrrolidinium Bromide (1c). Yield 5.6 g (97%).
White crystals, mp 92-95°С. IR spectrum, ν, cm-1: 1590, 1610, 3020, 3060 (Ph), 2230 (С≡С), 1640 (С=С),
1
1930, 720, 700, 680 (Ph); H NMR spectrum, δ, ppm (J, Hz): 7.61-7.50 (6Н, m, Н Ph); 7.45-7.25 (4Н, m,
Н Ph); 7.08 (1H, d, J = 15.6, =СНРh); 6.59 (1H, dt, J = 15.6, J = 7.6, СН2СН=); 4.80 (2Н, s, NСН2C≡C); 4.50
(2Н, d, J = 7.6, NСН2CH=); 3.95-3.80 (4Н, m, 2,5-СН2 pyrrolidine); 2.35-2.21 (4Н, m, 3,4-СН2 pyrrolidine).
Found, %: С 69.57; Н 6.59; Вr 21.22; N 4.06. C22H24BrN. Calculated, %: С 69.11; Н 6.33; Вr 20.90; N 3.66.
N-(3-Phenylpropen-2-yl)-N-(3-phenylpropyn-2-yl)morpholinium Bromide (1d). Yield 5.9 g (98%).
White crystals, mp. 178-181°С. IR spectrum, ν, cm-1: 1590, 1600, 3020, 3060 (Ph), 2230 (С≡С), 1630 (С=С),
1940, 740, 700, 680 (Ph). 1H NMR spectrum, δ, ppm (J, Hz): 7.61-7.56 (6Н, m, Н Ph); 7.45-7.25 (4Н, m, Н Ph);
7.13 (1H, d, J = 15.5, =СНРh); 6.58 (1H, dt, J = 15.5, J = 7.6, СН2СН=); 5.01 (2Н, s, NСН2C≡C); 4.67 (2Н, d,
J = 7.6, NСН2CH=); 4.15 (2Н, dt, J = 13.9, J = 4.8) and 4.07 (2Н, dt, J = 13.9, J = 4.8, (ОСН2)2); 3.80 (4Н, t,
J = 4.8, (NСН2)2). Found, %: С 66.81; Н 6.36; Вr 20.36; N 3.82. C22H24BrNО. Calculated, %: С 66.34; Н 6.07;
Вr 20.06; N 3.52.
Diethyl(3-phenylpropen-2-yl)(3-phenylpropyn-2-yl)ammonium Bromide (1e). Yield 5.5 g (96%).
White crystals, mp 143-145°С. IR spectrum, ν, cm-1: 1590, 1600, 3020, 3060 (Ph), 2230 (С≡С), 1640 (С=С),
1
1940, 740, 710, 690 (Ph). H NMR spectrum, δ, ppm (J, Hz): 7.61-7.53 (6Н, m, Н Ph); 7.45-7.26 (4Н, m,
Н Ph); 7.08 (1Н, d, J = 15.5, =СНРh); 6.53 (1Н, dt, J = 15.5, J = 7.5, СН2СН=); 4.73 (2Н, s, NСН2C≡C); 4.35
(2Н, d, J = 7.5, NСН2CH=); 3.62 (4Н, q, J = 7.2, (N(СН2СН3)2); 1.46 (6Н, t, J = 7.2, (N(СН2СН3)2). Found,
%: С 69.21; Н 7.08; Вr 21.09; N 3.90. C22H26BrN. Calculated, %: С 68.75; Н 6.82; Вr 20.79; N 3.64.
N-(3-Phenylpropen-2-yl)-N-(3-phenylpropyn-2-yl)piperidinium Bromide (1f). Yield 5.7 g (96%).
White crystals, mp 94-96°С. IR spectrum, ν, cm-1: 1590, 1610, 3020, 3060 (Ph), 2240 (С≡С), 1640 (С=С),
1
1940, 730, 720, 680 (Ph). H NMR spectrum, δ, ppm (J, Hz): 7.60-7.54 (6Н, m, Н Ph); 7.45-7.25 (4Н, m,
Н Ph); 7.08 (1H, d, J = 15.5, =СНРh); 6.54 (1H, dt, J = 15.5, J = 7.6, СН2СН=); 4.83 (2Н, s, NСН2C≡C); 4.50
(2Н, d, J = 7.6, NСН2CH=); 3.75 (4Н, t, J = 5.7, 2,6-СН2 piperidine); 2.09-1.92 (2Н, m) and 1.83-1.71 (4Н, m,
3,4,5-СН2 piperidine). Found, %: С 70.16; Н 6.26; Вr 20.51; N 3.88. C23H26BrN. Calculated, %: С 69.70;
Н 6.61; Br 20.16; N 3.53.
Cyclization of Salts 1a-f (General Method). A 3 N KOH aqueous solution (2 ml) was gradually added
to a solution of the salt 1a-f (12 mmol) in water (5 ml) and EtOH (2.5 ml) (salt:KOH molar ratio 2:1).
Spontaneous heating of the reaction mixture was not observed. The reaction mixture was maintained at 90-92°C
for 5-6 h, cooled, and extracted with Et2O (3×30 ml). Crystals of the products 2a,c,d and 3a,b separated from
the aqueous layer at room temperature. They were filtered off and recrystallized from absolute
1317

EtOH (compounds 2c,d, 3a,b) or water (compound 2a). Crystals of the starting salt 1a-f separated from the
filtrate at -2-3°C (~10-15% on the amount used in the reaction). They did not give a melting point depression in
a mixed melting test with an authentic sample of this salt. To isolate the product 2b, the aqueous layer after
extraction of the reaction mixture with ether and separation of the starting salt 1b was treated with an HBr
aqueous solution to an acidic reaction and evaporated to dryness. The salt 2b was extracted from the residue
with absolute ethanol and was precipitated from the alcohol extract with absolute ether in the form of a
honeylike substance. Attempts to obtain the salt 2b in crystalline form were unsuccessful. Therefore, the
substance isolated after decantation of the liquid phase was used for aqueous-alkaline cleavage (see below)
without further purification.
2,2-Dimethyl-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2a). Yield 2.65 g (65%). Shiny
crystals, mp 180-182°С. IR spectrum, ν, cm-1: 1580, 1600, 3000, 3020, 3060 (Аr), 670, 700, 740, 770, 1940
1
(Ph), 1630 (С=С). H NMR spectrum, δ, ppm (J, Hz): 7.45-7.39 (4Н, m, Н Ph); 7.37-7.30 (1H, m, Н Ph);
7.21-7.12 (2Н, m, Н-7,8); 7.03 (1Н, td, J = 7.3, J = 1.9, Н-6); 6.72 (1Н, q, J ≈ 1.5, Н-9); 6.54 (1Н, d, J = 7.6,
Н-5); 4.74 (1Н, d, J = 16.4) and 4.70 (1Н, d, J = 16.4, 1-СН2); 4.22 (1Н, d, J = 14.0, 4-СН); 3.89-3.82 (1Н, m)
and 3.65 (1Н, dd, J = 9.5, J = 7.0, 3-СН2); 3.81-3.70 (1Н, m, 3а-СН); 3.44 (3Н, s, СН3); 3.26 (3Н, s, СН3). 13C
NMR spectrum, δ, ppm: 139.8; 137.3; 135.5; 133.5; 128.5; 127.1; 126.9; 126.4; 126.3; 126.2; 121.3; 68.1 and
67.4 (СН2); 52.1 (СН3); 51.5 (СН3); 48.6 (СН); 41.9 (СН). Found, %: С 66.96; Н 5.87; Вr 22.91; N 4.04.
C20H22BrN. Calculated, %: С 67.42; Н 6.22; Вг 22.43; N 3.93.
2,2-Tetramethylene-4-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (2c). Yield 2.84 g
(62%). Shiny crystals, mp 163-164°С. IR spectrum, ν, cm-1: 1590, 1620, 3010, 3020, 3060 (Аr), 680, 710, 750,
1
770, 1930 (Ph), 1640 (С=С). H NMR spectrum, δ, ppm (J, Hz): 7.41-7.37 (4Н, m, Н Ph); 7.35-7.26 (1Н, m,
Н Ph); 7.16-7.09 (2Н, m, Н-7,8); 7.00 (Н, ddd, J = 7.7, J = 6.3, J = 2.5, Н-6); 6.67 (1Н, dt, J = 2.1, J= 2.1,
Н-9); 6.52 (Н, d, J = 7.6, Н-5); 4.81 (1Н, d, J = 15.8) and 4.79 (1Н, d, J = 15.8, 1-СН2); 4.19 (1Н, d, J = 14.5,
4-СН); 4.07-3.90 (2Н, m) and 3.85-3.55 (5Н, m, 2,5-СН2 pyrrolidine, 3-СН2, 3а-СН); 2.32-2.07 (4Н, m,
3,4-СН2 pyrrolidine). 13C NMR spectrum, δ, ppm: 139.7; 137.1; 134.9; 133.4; 128.5 (2С); 128.4; 127.0; 126.8;
126.4 (3С); 126.1; 121.3 (=СН); 65.5 and 64.8 (С-1); 62.9; 62.5; 48.6; 42.2; 21.5; 21.3. Found, %: С 68.64;
Н 5.97; Вr 21.41; N 3.79. C22H24BrN. Calculated, %: С 69.11; Н 6.33; Вr 20.90; N 3.66.
Spiro[morpholine-4′,2-(4-phenyl-3a,4-dihydrobenzo[f]isoindolinium)] Bromide (2d). Yield 3.44 g
(72%). Shiny crystals, mp 265-267°С. IR spectrum, ν, cm-1: 1590, 1620, 3010, 3020, 3060 (Аr), 680, 720, 760,
1
770, 1940 (Ph), 1630 (С=С). H NMR spectrum, δ, ppm (J, Hz): 7.46-7.39 (4Н, m, Н Ph); 7.38-7.31 (1Н, m,
Н Ph); 7.22-7.12 (2Н, m, Н-7,8); 7.03 (1Н, td, J = 7.4, J = 1.8, Н-6); 6.73 (1Н, dt, J = 2.0, J ≈ 2.0, Н-9); 6.52
(1Н, d, J = 7.7, Н-5); 5.04 (1Н, dt, J = 16.0, J= 1.5) and 4.86 (1Н, dt, J = 16.0, J= 1.5, 1-СН2); 4.25 (1Н, d,
J = 14.4, 4-СН); 4.07-3.71 (9Н, m) and 3.65-3.59 (2Н, m, N(СН2СН2)2O, 3-СН2, 3а-СН). Found, %: С 65.86;
Н 5.72; Вr 20.34; N 3.98. C22H24BrNО. Calculated, %: С 66.34; Н 6.07; Вr 20.06; N 3.52.
2,2-Diethyl-9-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (3a). Yield 2.90 g (65%). Shiny
crystals, mp 178-180°С. IR spectrum, ν, cm-1: 1570, 1610, 3000, 3020, 3060 (Ar), 680, 710, 740, 770, 1940
1
(Ph), 1640 (С=С). H NMR spectrum, δ, ppm (J, Hz): 7.49-7.43 (2Н, m, Н Ph); 7.41-7.35 (1H, m, Н Ph);
7.34-7.30 (2Н, m, Н Ph); 7.24 (Н, d, J =7.5, Н Ar); 7.16 (1H, td, J = 7.8, J = 1.3, Н Ar); 7.08 (1H, td, J = 7.5,
J = 1.3, H Ar); 6.80 (1H, dd, J = 7.6, J = 1.2, H Ar); 4.65 (1Н, dd, J = 16.0, J = 2.0) and 4.15 (1Н, dd, J = 16.0,
J = 2.5, 1-СН2); 4.29 (1Н, dd, J = 11.7, J = 8.5) and 3.73 (1Н, dd, J = 11.7, J = 9.4, 3-СН2); 3.65–3.43 (5H, m,
(СН3СН2)2N, 3a-СН); 3.04 (1H, dd, J = 14.7, J = 6.7) and 2.98 (1H, d, J = 14.7, 4-CH2); 1.35 (3H, t, J = 7.1)
and 1.26 (3H, t, J = 7.1, (СН3СН2)2N). 13C NMR spectrum, δ, ppm: 136.5; 134.8; 134.1; 133.7; 131.7, 128.8,
128.2; 127.4, 127.1, 126.3, 125.4; 64.7, 63.5 (1,3-СН2); 54.8, 53.7 ((СН3СН2)2N); 35.7, 31.8 (СНСН2); 8.4, 8.2
((СН3СН2)2N). Found, %: С 68.28; Н 6.45; Br 21.06; N 4.23. C22H26BrN. Calculated, %: С 68.75; Н 6.82;
Br 20.79; N 3.64.
2,2-Pentamethylene-9-phenyl-3a,4-dihydrobenzo[f]isoindolinium Bromide (3b). Yield 3.20 g
(68%). Shiny crystals, mp 284-286°С (abs. EtOH). IR spectrum, ν, cm-1: 1580, 1610, 3010, 3030, 3060 (Ar),
690, 720, 760, 780, 1940 (Ph), 1630 (С=С). 1H NMR spectrum, δ, ppm (J, Hz): 7.48-7.29 (5Н, m, H Ph); 7.24 (1Н,
1318

d, J = 7.4, H Ar); 7.15 (1Н, td, J = 7.4, J = 1.2, H Ar); 7.08 (1Н, td, J = 7.4, J = 1.2, H Ar); 6.80 (1Н, dd,
J = 7.4, J = 1.2, H Ar); 4.69 (1Н, dd, J = 15.9, J = 1.5) and 4.18 (1Н, dd, J = 15.9, J = 2.7, 1-CH2); 4.38 (1Н,
dd, J = 11.6, J = 8.2) and 3.75 (1Н, dd, J = 11.6, J = 9.3, 3-CH2); 3.74-3.45 (5Н, m, 3а-CH, 2,6-СН2
piperidine); 3.06 (1Н, dd, J = 14.8, J = 6.5) and 2.93 (1Н, d, J = 14.8, 4-CH2); 2.01-1.81 (2Н, m) and 1.77-1.52
13
(4Н, m, 3,4,5-CН2 piperidine). C NMR spectrum, δ, ppm: 136.6; 134.8; 134.2; 133.8; 131.5; 128.8 (2С, Ph);
128.3 (2С, Ph); 127.5 (СН, Ph); 127.4 (СН, Ar); 127.1 (СН, Ar); 126.3 (СН, Ar); 125.3 (СН, Ar); 65.1 and
64.1 (С-1,3); 60.4 and 59.2 (2,6-СН2 piperidine); 35.3 (С-3а); 31.9 (С-4); 20.8, 20.6. Found, %: С 69.22;
Н 6.24; Br 20.45; N 4.08. C23H26BrN. Calculated, %: С 69.70; Н 6.61; Br 20.16; N 3.53.
Aqueous-Alkaline Cleavage of Salts 2a,c,d and 3a,b (General Method). A 25% KOH solution (2 g
of KOH in 6 ml of H2O) (~8 ml) was added to the salt 2a,c,d or 3a,b (6 mmol) in H2O (4 ml). The mixture was
maintained at 110-120°C for 1.5 h, and the water was then distilled from it with the periodic addition of new
portions (10-15 ml) of water. The temperature of the reaction mixture was raised to 140-145°C for a few
minutes (to complete the process). The reaction mixture and its distilled part were then extracted with Et2O
(3×50 ml). The combined extract was shaken with a 15% HCl solution, and the hydrochloric acid layer was
separated, made alkaline, and extracted with Et2O. The extract was washed with water and dried over MgSO4. A
mixture of the isomeric amines 4, 5a,c-e and the amine 4f, produced during cleavage of the salt 3b, were
isolated from the residue by vacuum distillation after removal of the ether.
After cyclization of the salt 1b under conditions of base catalysis aqueous-alkaline cleavage of the salt
2b was performed directly without its isolation. The aqueous-alkaline cleavage and also the isolation of the
isomeric amines 4b and 5b from the reaction mixture were carried out according to the method described above.
2-(Dimethylaminomethyl)-3-methyl-1-phenylnaphthalene (4a) and 3-(Dimethylaminomethyl)-
2-methyl-1-phenylnaphthalene (5a). Total yield 1.1 g (65%), bp 177-179°С (1.0-1.5 mm Hg). IR spectrum, ν,
1
cm-1: 680, 700, 730, 1940, 880, 1600, 3030, 3060 (Ar). Ratio of isomers 4а:5а, 4:1. H NMR spectrum of
mixture of compounds 4a and 5a, δ, ppm (J, Hz): 7.75 (0.2Н, br. d, J = 8.1, Н Ar (5а)); 7.70 (0.8Н, br. d,
J = 8.1, Н Ar (4а)); 7.68 (0.2Н, s, Н-4 (5а)); 7.61 (0.8Н, s, Н-4 (4а)); 7.48-7.38 (3Н, m), 7.36-7.31 (1Н, m),
and 7.23-7.16 (4H, m, Н Ar (4a+5a)); 3.53 (0.4Н, s, Ме2NСН2 (5a)); 3.31 (1.6Н, s, Me2NСН2 (4a)); 2.64
(2.4Н, s, 3-СН3 (4a)); 2.28 (1.2Н, s, N(СН3)2 (5a)); 2.20 (0.6Н, s, 2-СН3 (5a)); 2.01 (4.8Н, s, N(СН3)2 (4a)).
Found, %: С 87.62; Н 7.89; N 5.24. C20H21N. Calculated, %: С 87.23; Н 7.69; N 5.09.
2-(Dipropylaminomethyl)-3-methyl-1-phenylnaphthalene (4b) and 3-(Dipropylaminomethyl)-
2-methyl-1-phenylnaphthalene (5b). Total yield 1.3 g (67%), bp 185-187°С (1 mm Hg). IR spectrum, ν, cm-1:
680, 710, 740, 1930, 890, 1610, 3040, 3060 (Ar). Ratio of isomers 4b:5b, 7:3. 1H NMR spectrum of mixture of
compounds 5b and 4b, δ, ppm (J, Hz): 7.76 (0.3Н, s, Н-4 (5b)); 7.59 (0.7Н, s, Н-4 (4b)); 7.74 (0.3Н, d, J = 8.2,
Н Ar (5b)); 7.70 (0.7Н, d, J = 8.2, Н Ar (4b)); 7.50-7.29 (4Н, m, Н Ar (4b+5b)); 7.22-7.13 (4Н, m, Н Ar
(4b+5b)); 3.69 (0.6Н, s, Pr2NСН2 (5b)); 3.49 (1.4Н, s, Pr2NСН2 (4b)); 2.67 (2.1Н, s, 3-СН3 (4b)); 2.21 (0.9Н,
s, 2-СН3 (5b)); 2.48-2.42 (1.2Н, m, (CH3CH2СН2)2N (5b)); 2.19-2.13 (2.8Н, m, (CH3CH2СН2)2N (4b));
1.56-1.44 (1.2Н, m, (CH3CH2СН2)2N (5b)); 1.33-1.21 (2.8Н, m, (CH3CH2СН2)2N (4b)); 0.87 (1.8Н, t, J = 7.3,
(CH3CH2СН2)2N (5b)); 0.75 (4.2Н, t, J = 7.3, (CH3CH2СН2)2N (4b)). Found, %: С 87.36; Н 9.03; N 4.43.
C24H29N. Calculated, %: С 86.96; Н 8.82; N 4.23.
3-Methyl-2-pyrrolidinomethyl-1-phenylnaphthalene (4c) and 2-Methyl-3-pyrrolidinomethyl-
1-phenylnapthalene (5c). Total yield 1.2 g (67%), bp 195–197°С (1-2 mm Hg). IR spectrum, ν, cm-1: 670, 700,
1
730, 1940, 880, 1600, 3030, 3050 (Ar). Ratio of isomers 4c:5c, 68:32. H NMR spectrum of mixture of
compounds 5c and 4c, δ, ppm (J, Hz): 7.74 (0.32Н, br. d, J = 8.1, H Ar (5c)); 7.69 (0.68Н, br. d, J = 8.1, H Ar
(4c)); 7.71 (0.32Н, s, Н-4 (5с)); 7.59 (0.68Н, s, Н-4 (4c)); 7.50-7.38 (3Н, m), 7.36-7.29 (1Н, m), and 7.23-7.14
(4H, m, Н Ar (4c+5c)); 3.74 (0.64Н, s, NСН2Ar (5с)); 3.51 (1.36Н, s, NСН2Ar (4с)); 2.60-2.54 (1.28Н, m,
2,5-СН2 pyrrolidine (5с)); 2.30-2.23 (2.72Н, m, 2,5-СН2 pyrrolidine (4с)); 2.65 (2.04Н, s, 3-СН3 (4с)); 2.21
(0.96Н, s, 2-СН3 (5с)); 1.82-1.76 (1.28Н, m, 3,4-СН2 pyrrolidine (5с)); 1.66-1.54 (2.72Н, m, 3,4-СН2
pyrrolidine (5с)). Found, %: С 88.05; Н 7.92; N 4.85. C22H23N. Calculated, %: С 87.66; Н 7.69; N 4.65.
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N-[(3-Methyl-1-phenyl-2-naphthyl)methyl]morpholine (4d) and N-[(2-Methyl-1-phenyl-3-naphthyl)-
methyl]morpholine (5d). Total yield 1.3 g (68%), bp 145–146°С (1 mm Hg), mp 65–67°С. IR spectrum (thin
film), ν, cm-1: 680, 700, 730 (Ph), 700, 730, 1940, 890, 1590, 3020, 3060 (Ar). Ratio of isomers 4d:5d, 7:3. 1H
NMR spectrum of mixture of compounds 4d and 5d, δ, ppm (J, Hz): 7.75 (0.3Н, br. d, J = 8.1, Н Ar (5d)); 7.71
(0.7Н, br. d, J = 8.1, H Ar (4d)); 7.68 (0.3Н, s, H-4 (5d)); 7.62 (0.7Н, s, Н-4 (4d)); 7.50-7.39 (3Н, m), 7.37-7.32
(1Н, m), and 7.24-7.14 (4H, m, Н Ar (4d+5d)); 3.62-3.59 (1.2H, m, О(СН2)2 (5d)); 3.47-3.44 (2.8Н, m,
О(СН2)2 (4d)); 3.62 (0.6Н, s, NCH2Ar (5d)); 3.40 (1.4Н, s, NСН2Ar (4d)); 2.66 (2.1Н, s, 3-СН3 (4d); 2.50-2.47
(1.2H, m, (СН2)2NCH2Ar (5d)); 2.22 (0.9Н, s, 2-СН3 (5d)); 2.20-2.17 (2.8Н, m, (СН2)2NCH2Ar (4d)). Found,
%: С 83.65; Н 7.53; N 4.66. C22H23NО. Calculated, %: С 83.24; Н 7.30; N 4.41.
2-(Diethylaminomethyl)-3-methyl-1-phenylnaphthalene (4e) and 3-(Diethylaminomethyl)-2-methyl-
1-phenylnaphthalene (5e). Total yield 1.2 g (66%), bp 175-177°С (1-2 mm Hg). IR spectrum, ν, cm-1: 690,
1
710, 740, 1930, 870, 1590, 3020, 3050 (Ar). Ratio of isomers 4е:5е, 69:31. H NMR spectrum of mixture of
compounds 4e and 5e, δ, ppm (J, Hz): 7.75 (0.31Н, s, Н-4 (5е)); 7.59 (0.69Н, s, Н-4 (4е)); 7.75 (0.31Н, d,
J = 8.2, Н Ar (5е)); 7.69 (0.69Н, d, J = 8.2, Н Ar (4е)); 7.50-7.29 (4Н, m) and 7.23-7.13 (4Н, m, Н Ar (4е+5е));
3.69 (0.62Н, s, Et2NСН2 (5е)); 3.47 (1.38Н, s, Et2NСН2 (4е)); 2.59 (1.24Н, q, J = 7.1, (СН3СН2)2N (5е)); 2.30
(2.76Н, q, J = 7.1, (СН3СН2)2N (4е)); 2.67 (2.07Н, s, 3-СН3 (4е)); 2.21 (0.93Н, s, 2-СН3 (5е)); 1.07 (1.86Н, t,
J = 7.1, (СН3СН2)2N (5е)); 0.82 (4.14Н, t, J = 7.1, (СН3СН2)2N (4е)). Found, %: С 87.49; Н 8.53; N 4.87.
C22H25N. Calculated, %: С 87.08; Н 8.30; N 4.62.
3-Methyl-1-phenyl-2-piperidinomethylnapthalene (4f). Yield 1.4 g (75%), bp 155-157°С (1-2 mm
Hg), mp 85-87°С. IR spectrum, ν, cm-1: 680, 700, 730, 1940, 880, 1600, 3010, 3060 (Ar). 1H NMR spectrum, δ,
ppm (J, Hz): 7.60 (1Н, s, Н-4); 7.69 (1Н, d, J = 8.2, Н Ar); 7.47-7.30 (4Н, m, Н Ar); 7.21-7.12 (4Н, m, Н Ar);
3.33 (2Н, s, NСН2Ar); 2.65 (3Н, s, 3-СН3); 2.19-2.13 (4Н, m, 2,6-СН2 piperidine); 1.45-1.36 (4Н, m, 3,5-СН2
piperidine); 1.35-1.28 (2Н, m, 4-СН2 piperidine). Found, %: С 87.96; Н 8.22; N 4.59. C23H25N. Calculated, %:
С 87.57; Н 7.99; N 4.44.
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