Base catalyzed intramolecular cycloaddition of dialkyl(4-hydroxybutyn2-yl) [3-(p-tolyl)propyn- - 2-yl]ammonium chlorides and intramolecular recyclization of the products obtained

Article abstract of DOI:10.1007/s10593-010-0486-1

Dialkyl(4-hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]ammonium chlorides undergo a diene synthesis type intramolecular cyclization in aqueous base medium to give 2,2-dialkyl-4-hydroxymethyl-6-methyl-benzo[f]isoindolinium chlorides. Under conditions of aqueo

Full text of DOI:10.1007/s10593-010-0486-1

Chemistry of Heterocyclic Compounds, Vol. 46, No. 2, 2010
BASE CATALYZED INTRAMOLECULAR CYCLOADDITION
OF DIALKYL(4-HYDROXYBUTYN-2-YL)[3-(p-TOLYL)PROPYN-
2-YL]AMMONIUM CHLORIDES AND INTRAMOLECULAR
RECYCLIZATION OF THE PRODUCTS OBTAINED
E. O. Chukhajian1*, L. V. Ayrapetyan1, El. O. Chukhajian1, and H. A. Panosyan2
Dialkyl(4-hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]ammonium chlorides undergo a diene synthesis
type intramolecular cyclization in aqueous base medium to give 2,2-dialkyl-4-hydroxymethyl-6-methyl-
benzo[f]isoindolinium chlorides. Under conditions of aqueous base fission intramolecular cyclization of
the latter gives 4-dialkylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furans.
Keywords: 4-dialkylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furans, dialkyl(4-hydroxybutyn-
2-yl)[3-(p-tolyl)propyn-2-yl]ammonium chlorides, 2,2-dialkyl-4-hydroxymethyl-6-methylbenzo[f]iso-
indolinium chlorides, intramolecular cyclization, base catalysis, recyclization.
We have found that CH2C≡CCH2OH groups can take part in intramolecular cyclization [1-5] and that
the cyclization products can recyclize intramolecularly in conditions of aqueous base fission [2-6].
Opening of the ring occurs with intramolecular nucleophilic attack by an alkoxy anion formed in basic
medium, the recyclization not involving ring expansion or contraction but the formation of a dihydrofuran ring
in place of the pyrrole fragment. Based on this reaction we have developed an original synthetic route for amines
with a hydrogenated furan ring pharmacophore [2-6]. It should be noted that only one example is known of a
recyclization of a purely intramolecular nature, i.e. the thermal reaction of iminobenzylfurandiones to
4-allylpyrrole-2,3-diones [7].
Many examples have been reported in the literature of the recyclization of carbo- and, particularly,
heterocyclic compounds, some of which are collected in review articles [8-12]. In all cases the action of various
_______
* To whom correspondence should be addressed, e-mail: shhl@mail.ru.
1Institute of Organic Chemistry, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, Yerevan 0091, Armenia.
2Molecular Structure Research Center, National Academy of Sciences of Armenia, Yerevan 0014, Armenia;
e-mail: henry@msrc.am.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 187-194, February, 2010. Original
article submitted January 16, 2009; revision submitted May 28, 2009.
0009-3122/10/4602-0151©2010 Springer Science+Business Media, Inc.
151

nucleophilic, electrophilic, or dipolar reagents leads to ring opening followed by a closure. The process is often
accompanied by ring expansion or contraction with the introduction of a heteroatom into it or with exchange of
an existing heteroatom for another.
In continuation of our study of the above reaction this report concerns alkylation of the amines 1a-f, the
dialkyl(4-hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]ammonium chlorides 2a-f, and a study of the recyclization
of the synthesized 2,2-dialkyl-4-hydroxymethyl-6-methylbenzo[f]isoquinolinium salts 3a-f. In addition to
resolving preparative questions it was also interesting to determine the effect of a methyl substituent in the para
position of the benzene ring on the cyclization of salt 2.
It was found that cyclization of salts 2a-e occurs in the presence of aqueous KOH at a molar ratio of salt 2 to
KOH of about 1:1, i.e. more forcing conditions when compared with their 3-R1-substituted analogs (R1 = phenyl,
p-chlorophenyl, alkenyl) in which this ratio was 5: 1 [1-4].
CH2
OH
C
C
CH2
CH2
–
+
R2N
OH

Me
ClCH2C
+
CCH2OH
R2NCH2C
C
C
C
Me
–
Cl
1a–f
2a–f
HO
2
O
O
1
5
3
1
9
6
Me
6
–
3
+
OH
Me
Me
R2N
X
8
7
+
R2N
7
R2N
4
8
9
5
3a–f
4a–f
1–4 a R = Me, b R = Et, c R = Pr, d R + R = (CH2)4,
e R + R = (CH2)5, f R + R = (CH2)2O(CH2)2; 3a–d, f X = Cl, e X = Br
The lower reactivity of compounds 2a-e is in line with the scheme proposed before for the cyclization of
their analogs (3, R1 = phenyl, alkenyl), according to which the CH2C≡CR1 takes part directly in the cyclization
and base is the driving force for the process which includes electron transfer via a six-membered cyclic
mechanism [13-15]. Evidently the methyl substituent in the para position of the benzene ring in salts 2a-f
unfavourably affects their cyclization because the shift of electrons caused by the positive inductive and
hyperconjugative effects of a CH3 group opposes the electron transfer in the six-membered cyclic mechanism.
OH
+
N
H
H
C
H
–
OH
Previously, a kinetic investigation of the cyclization of dimethyl(propargyl)[3-(p-tolyl)propyn-2-yl]-
ammonium bromide has also shown that the presence of a methyl group in the para position of the benzene ring
decreases the reaction rate [16]. It should be noted that, in contrast to the ammonium, pyrrolidinium, and
piperidinium salts discussed 2a-e, the cyclization of the morpholinium substituted salt 2f occurs with a vigorous
exotherm, even with a molar ratio of salt 2f to KOH of 5:1. The observed effect can be explained by the marked
inductive effect of a morpholine fragment associated with the presence of the unshared electron pair of the
oxygen atom.
152

It was also found that only the salts 2e,f gave the corresponding products 3e,f in a crystallizable state
while after cyclization of salt 2e the reaction product was acidified with hydrobromic acid to give the
hydrobromide salt 3e. Salts 3a-d could not be separated and characterized because of their hygroscopic
properties and the salts form a glassy mass. All of the salts 3a-f undergo recyclization without their separation
from the reaction mixture following cyclization of compounds 2a-f. The recyclizations were performed in the
presence of an equimolar or two fold amount (in the case of salt 3f) of KOH at 80-85ºC and with an overall yield
of 62-70% for amines 4b-f while the yield of amine 4a was only 32% due to strong tarring. It should be noted
that the products 4a-f are formed in 8-15% yield via the above reported cyclization of salts 2a-f with a five fold
excess of salt 2 with respect to KOH.
The composition and structure of the novel compounds 1c,d,f, 2a-f, 3e-f, 4a-f were confirmed from
elemental analytical data and also from their IR spectra and NMR spectra of compounds 2e,f, 3e,f and 4a-f.
1
Assignment of the signals in the H NMR and 13C NMR spectra of salts 3e,f and amines 4a-f were carried out
from their 2D COSY, NOESY, and HMQC spectra.
The IR spectra of salts 3a,f show the absence of the absorption bands in the region 2220-2240
(disubstituted acetylene bond) and 810-840 cm-1 (para-substituted benzene ring) which are characteristic of the
salts 2a-f but there are present bands at 820 and 870 cm-1 for the 1,2,4- and penta-ubstituted benzene rings
respectively. Salts 2, 3 show absorptions at 1040, 1080, and 3200-3500 (OH groups), 1580, 1600, and
3130-3150 cm-1 (aromatic ring). The spectra of amines 4a-f show absorption bands at 720-800 and 870 cm-1
(1,2,4- and penta-substituted benzene rings respectively) as well as bands at 1010, 1050, 1060-1110 cm-1 ( ring
C–O-C) and at 1500, 1580, 1600 and 3030-3040 cm-1 (aromatic ring).
EXPERIMENTAL
1
13
IR spectra were recorded on a UR-20 spectrometer for KBr tablets or in vaseline oil. H and C NMR
spectra were recorded on a Varian Mercury VX 300 instrument (300 and 75 MHz respectively) at 300 K for
solutions in DMSO-d6–CCl4 (1:3) and were referred to the residual non-deuterated solvent signal.
The starting amines 1a,b,e were synthesized via a Mannich reaction as reported in [17] and 4-chloro-
2-butynol was obtained using a reported method [18].
Synthesis of the Starting Amines (1c,d,f) (General Method). A mixture of p-tolylacetylene
(120 mmol), paraformaldehyde (118 mmol), the corresponding secondary amine (120 mmol), ferric chloride
(0.6 g), copper diacetate (0.4 g), and dioxane (80 ml) was held for 62 h at 90-92ºC, acidified with 20% aqueous
HCl, and solvent was distilled off under reduced pressure. After removal of organic admixtures by extracting
with ether (2×50 ml), the residue was basified with 20% aqueous NaOH solution and extracted with ether
(3×50 ml). Drying over MgSO4, evaporation of the extract, and vacuum distillation of the residue gave the target
amine 1.
Dipropyl[3-(p-tolyl)propyn-2-yl]amine (1c). Yield 16.90 g (62%); bp 135-136ºC (1-2 mm Hg),
nD20 1.5212, mp of picrate 98-102ºC (EtOH). IR spectrum, , cm-1: 810, 840, 1560, 1580, 2230, 3020. 1H NMR
spectrum, , ppm (J, Hz): 7.23 and 7.07 (2H, m and 2H, m, C6H4); 3.51 (2H, s, CH2C≡CAr); 2.44 (4H, m,
N(CH2)2); 2.34 (3H, s, Ar-CH3); 1.47 (4H, sext., J = 7.3, CH2CH3); 0.92 (6H, t, J = 7.3, CH2CH3). Found, %:
C 84.18; H 10.32; N 6.26. C16H23N. Calculated, %: C 83.79; H 10.11; N 6.11.
N-[3-(p-Tolyl)propyn-2-yl]pyrrolidine (1d). Yield 10.20 g (43%); bp 157-158ºC (1 mm Hg),
nD20 1.5570, mp of picrate 138-140ºC (EtOH). IR spectrum, , cm-1: 810-840, 1560, 1600, 2220, 3030. 1H NMR
spectrum, , ppm: 7.24 and 7.07 (2H, m and 2H, m, C6H4); 3.54 (2H, s, CH2C≡CAr); 2.61 (4H, m, N(CH2)2);
2.35 (3H, s, Ar-CH3); 1.78 (4H, m, N(CH2CH2)2) . Found, %: C 84.78; H 8.76; N 7.19. C14H17N. Calculated, %:
C 84.37; H 8.54; N 7.03.
153

20
N-[3-(p-Tolyl)propyn-2-yl]morpholine (1f). Yield 12.05 g (46.7%); bp 151-153ºC (3-4 mm Hg), nD
1.5632, mp picrate 157-158ºC (EtOH). IR spectrum, , cm-1: 810-840, 1560, 1600, 2230, 3030. H NMR
spectrum, , ppm: 7.26 and 7.09 (2H, m and 2H, m, C6H4); 3.63 (4H, m, O(CH2)2); 3.43 (2H, s, CH2C≡CAr);
2.53 (4H, m, N(CH2)2); 2.35 (3H, s, Ar-CH3). Found, %: C 78.54; H 8.19; N 6.71. C14H17NO. Calculated, %:
C 78.14; H 7.96; N 6.51.
1
Alkylation of Amines 1a-f by 4-Chloro-2-butynol to Give Salts 2a-f (General Method).
Chromatographically pure 4-chloro-2-butynol (30 mmol) was added to a solution of the amine 1a-f (15 mmol)
in acetonitrile (10 ml). The reaction mixture was held at 90-92ºC for 2-3 h and then for salts 2a-e the solvent
was removed under reduced pressure. The salts 2a-e were washed with absolute ether (3 x 20 ml) and dried over
P2O5. Salt 2f crystallized upon cooling the reaction mixture and was filtered off and recrystallized from absolute
alcohol. Salts 2a-e are hygroscopic and it was not possible to determine their melting points.
(4-Hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]dimethylammonium chloride (2a). Yield 4.10 g
(98%). IR spectrum, , cm-1: 810-840, 1560, 1600, 2230, 3030, 3100-3500. Found, %: C 69.57; H 7.46;
Cl 13.01; N 5.21. C16H20ClNO. Calculated, %: C 69.18; H 7.26; Cl 12.76; N 5.04.
(4-Hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]diethylammonium chloride (2b). Yield 3.76 g (82%).
IR spectrum, , cm-1: 810-850; 1560, 1600, 2220, 3020, 3100-3500. Found, %: C 71.08; H 8.12; Cl 11.86,
N 4.76. C18H24ClNO. Calculated, %: C 70.69; H 7.91; Cl 11.59; N 4.58.
(4-Hydroxybutyn-2-yl)[3-(p-tolyl)propyn-2-yl]dipropylammonium chloride (2c). Yield 4.40 g
(88%). IR spectrum, , cm-1: 810-840, 1540, 1600, 2220, 3030, 3200-3500. Found, %: C 72.34; H 8.66;
Cl 10.94; N 4.36. C20H28ClNO. Calculated, %: C 71.94; H 8.45; Cl 10.62; N 4.19.
N-(4-Hydroxybutyn-2-yl)-N-[3-(p-tolyl)propyn-2-yl]pyrrolidinium chloride (2d). Yield 3.91 g
(86%). IR spectrum, , cm-1: 810-840, 1540, 1600, 2220, 3030, 3200-3500. Found, %: C 71.56; H 7.46;
Cl 11.99; N 4.76. C18H22ClNO. Calculated, %: C 71.16; H 7.25; Cl 11.67; N 4.61.
N-(4-Hydroxybutyn-2-yl)-N-[3-(p-tolyl)propyn-2-yl]piperidinium chloride (2e). Yield 4.41 g (93%).
IR spectrum, , cm-1: 810-840, 1550, 1600, 2220, 3020, 3200-3500. 1H NMR spectrum, , ppm (J, Hz): 7.46 and
7.17 (2H, m and 2H, m, C6H4); 5.60 (1H, br. s, OH); 4.96 (2H, s, CH2C≡CAr); 4.72 (2H, t, J = 1.9,
NCH2C≡CCH2); 4.18 (2H, t, J = 1.9, CH2OH); 3.82 (4H, m, N(CH2)2); 2.38 (3H, s, Ar-CH3); 1.96 (4H, m,
N(CH2CH2)2); 1.73 (2H, m, N(CH2CH2)2CH2). Found, %: C 72.21; H 7.83; Cl 11.47; N 4.45. C19H24ClNO.
Calculated, %: C 71.81; H 7.61; Cl 11.15; N 4.41.
N-(4-Hydroxybutyn-2-yl)-N-[3-(p-tolyl)propyn-2-yl]morpholinium chloride (2f). Yield 4.00 g
1
(83%); mp 198-200ºC (abs. EtOH). IR spectrum, , cm-1: 810-840, 1600, 2220, 3020, 3200-3500. H NMR
spectrum, , ppm (J, Hz): 7.48 and 7.18 (2H, m and 2H, m, C6H4); 5.57 (1H, br. s, OH); 5.13 (2H, s,
CH2C≡CAr); 4.87 (2H, t, J = 2.0, N(CH2C≡CCH2); 4.18 (2H, t, J = 2.0, CH2OH); 4.05 (4H, m, N(CH2)2); 3.84
(4H, m, O(CH2)2); 2.39 (3H, s, Ar-CH3). Found, %: C 68.01; H 7.11; Cl 11.33; N 4.61. C18H22ClNO2.
Calculated, %: C 67.61; H 6.89; Cl 11.08; N 4.38.
Cyclization of Salts 2a-f to Salts 3a-f (General Method). An aqueous solution of KOH (3N, 0.7 ml)
was added to a solution of salt 2a-f (10 mmol) in water (4 ml) (5:1 molar ratio of salt to KOH). The mixture was
heated to 50ºC. For salt 2f, the temperature was raised to 100ºC and in the remaining cases to 85ºC. After
cooling to room temperature, the reaction mixture was extracted with ether and dichloromethane (2:1, 3×30 ml).
Titration of the extract with 0.1N H2SO4 showed that the extract contained 8-15% of amine 4a-f, the picrate of
which did not depress the melting point of the picrate of amine 4a-f prepared by recyclization of salts 3a-f (see
below). After extraction, the aqueous solution was acidified with 20% aqueous HCl (or HBr in the case of salt
2e). The cyclization products 3e,f were separated in the crystalline state, filtered, washed on the filter with water,
and dried. For separation of the products 3a-d the acidified mass was evaporated to dryness and the residue was
extracted with absolute ethanol. Addition of ether to the alcohol extract gave the glassy salts 3a-d. They could
not be prepared and characterized in the crystalline state.
154

4-Hydroxymethyl-6-methyl-2,2-pentamethylenebenzo[f]isoindolinium Bromide (3e). Yield 2.50 g
1
(69%); mp 263-264ºC. IR spectrum, , cm-1: 720, 870, 1030, 1050, 1080, 1580, 3040, 3200-3500. H NMR
spectrum, , ppm (J, Hz): 9.33 (1H, br. s, OH); 8.04 (1H, s, H-9); 7.93 (1H, d, J = 8.4, H-8); 7.52 (1H, d,
J = 1.8, H-5); 7.45 (1H, dd, J1 = 8.4, J2 = 1.8, H-7); 5.44 and 5.34 (2H, t, J = 2.9 and 2H, dd, J1 = 3.2, J2 = 2.5,
H-1 and H-3); 4.34 (2H, d, J = 5.3, CH2OH); 3.40 and 3.02 (2H, m and 2H, m, -H piperidino); 2.50 (3H, s,
CH3); 1.86-1.59 and 1.38 (5H, m and 1H, m, ,-H piperidino). 13C NMR spectrum, , ppm: 137.45, 136.89,
134.77, 131.19, 130.62, 128.58, 128.42, 127.32, 122.91 and 120.76 (C arom.); 73.50 and 73.06 (C-1 and C-3);
56.98 (OCH2); 52.03 (C- piperidino); 22.38 (C- piperidino); 21.37 (C- piperidino) and 21.17 (CH3). Found,
%: C 63.21; H 7.04; Br 22.38; N 4.05. C19H24BrNO. Calculated, %: C 62.99; H 6.68; Br 22.05; N 3.87.
4-Hydroxymethyl-6-methylspirobenzo[f]isoindoline-2,4'-morpholinium chloride (3f). Yield 2.30 g
(73%), mp 158-159ºC. IR spectrum, , cm-1: 720; 870, 1020, 1050, 1070, 1110, 1580, 1600, 3030, 3200-3400.
1H NMR spectrum, , ppm (J, Hz): 7.88 (1H, s, H-9); 7.75 (1H, d, J = 8.4, H-8); 7.75 (1H, d, J = 1.6, H-5); 7.31
(1H, dd, J1 = 8.4, J2 = 1.6, H-7); 5.88 (1H, br. s, OH); 5.53 and 5.21 (2H, s and 2H, s H-1, H-3); 4.97 (2H, s,
CH2OH); 4.14 and 4.01 (2H, dt, J1 = 13.8, J2 = 5.0, and 2H dt, J1 = 13.8, J2 = 4.6, NCH2 morpholino); 3.77 (4H,
t, J = 4.8, OCH2 morpholino); 2.54 (3H, s, CH3). 13C NMR spectrum, , ppm: 135.32, 132.96, 131.29, 131.04,
129.27, 128.63, 127.88, 127.82, 122.88 and 121.26 (C arom.); 66.1 and 65.8 (C-1 and C-3); 61.39 (OC
morpholino); 58.36 (NC morpholino); 58.09 (4-CH2); 56.98 (4-CH2) and 21.48 (CH3). Found, %: C 68.02;
H 7.16; Cl 11.33; N 4.61. C18H22ClNO2. Calculated, %: C 67.61; H 6.93; Cl 11.08; N 4.38.
Recyclization of Salts 3a-f to Amines 4a-f (General Method). Salts 3a-f were prepared by cyclization
of compounds 2a-f (10 mmol) in water (3 ml) and underwent cyclization without separation from the reaction
mixture after extraction of the latter with a mixture of ether and dichloromethane (3:1, 2×25 ml). The product
obtained contained the salts 3a-e and was treated with a solution of KOH (10 mmol) in water (2 ml) (in the case
of salt 3f a solution of KOH (20 mmol) in water (4 ml)) and the mixture was held for 3-3.5 h at 80-85°C. Tarring
occurred with salt 3a. The cooled product was extracted with a mixture of ether and dichloromethane (3:1,
3×25 ml) and the extract was washed with water. In all cases, titration of the extract with 0.1N H2SO4 indicated
the presence of 5.4-5.5 mmol (54-55%) of amine 4b-f. The ether extract was dried over MgSO4. Evaporation of
solvent gave amines 4c,f in the crystalline state and were recrystallized from a mixture of ether and
dichloromethane (2:1). Amines 4a,b,d,e were separated from the residue by distillation. After distillation,
amines 4b,e crystallized and were recrystallized from a mixture of ether and dichloromethane.
4-Dimethylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furan (4a). Yield 0.77 g (32%); bp
1
128-130ºC (1-2 mm Hg). IR spectrum, , cm-1: 730, 790, 870, 1060, 1100, 1580, 1600, 3030. H NMR
spectrum, , ppm (J, Hz): 7.71 (1H, d, J = 8.4, H-6); 7.53 (1H, s, H-5); 7.31 (1H, d, J = 1.9, H-9); 7.25 (1H, dd,
J1 = 8.4, J2 = 1.9, H-7); 5.35 (2H, t, J = 3.2, H-3); 5.20 (2H, t, J = 3.2, H-1); 3.45 (2H, s, 4-CH2); 2.51 (3H, s,
8-CH3); 2.21 (6H, s, NCH3). 13C NMR spectrum, , ppm: 136.04, 134.92, 133.72, 130.82, 130.12, 127.57.
127.16, 126.51, 126.37, and 122.30 (C arom); 73.42 and 72.32 (C-1 and C-3); 62.31 (4-CH2); 44.88 (NCH3);
21.23 (8-CH3). Found, %: C 80.02; H 8.14; N 6.03. C16H19NO. Calculated, %: C 79.63; H 7.94; N 5.81.
4-Diethylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furan (4b). Yield 1.70 g (62%); bp
135-137ºC (3-4 mm Hg), mp 123-125 (ether–dichloromethane), mp picrate 187-190ºC (EtOH). IR spectrum, ,
cm-1: 720, 760, 870, 1050, 1100, 1600, 3030. 1H NMR spectrum, , ppm (J, Hz): 7.70 (1H, d, J = 8.4, H-6); 7.53
(1H, s, H-5); 7.31 (1H, d, J = 1.8, H-9); 7.25 (1H, dd, J1 = 8.4, J2 = 1.8, H-7); 5.34 (2H, t, J = 3.1, H-3); 5.22
(2H, t, J = 3.1, H-1); 3.60 (2H, s, 4-CH2); 2.51 (3H, s, 8-CH3); 2.50 (4H, q, J = 7.1, CH2CH3); 1.04 (6H, t,
J = 7.1, CH2CH3). Found, %; C 80.65; H 8.83; N 5.45. C18H23NO. Calculated, %; C 80.26; H 8.61; N 5.21.
4-Dipropylaminomethyl-8-methyl-1,3-dihydronaphtho[1,2-c]furan (4c). Yield 1.90 g (64.1%); mp
97-98ºC (ether–dichloromethane), mp picrate 184-185ºC (EtOH). IR spectrum, , cm-1: 770, 800, 870, 1050,
1110, 1580, 3040. 1H NMR spectrum, , ppm (J, Hz): 7.70 (1H, d, J = 8.3, H-6); 7.53 (1H, s, H-5); 7.31 (1H, d,
J = 1.8, H-9); 7.25 (1H, dd, J1 = 8.3, J2 = 1.8, H-7); 5.34 (2H, t, J = 3.0, H-3); 5.22 (2H, t, J = 3.0, H-1); 3.58
(2H, s, 4-CH2); 2.51 (3H, s, 8-CH3); 2.36 (4H, t, J = 7.3, NCH2); 1.48 (4H, sext., J = 7.3, CH2CH3); 0.85 (6H, t,
155

J = 7.3, CH2CH3). 13C NMR spectrum, , ppm: 135.82, 134.67, 133.60, 130.87, 130.77, 127.41, 127.01, 126.38,
126.21 and 122.22 (C arom.); 73.47 and 72.23 (C-1 and C-3); 57.62 (4-CH2); 55.36 (C- propyl); 21.19
(8-CH3); 19.50 (C- propyl); 11.47 (C- propyl). Found, %: C 81.16; H 9.38; N 4.86. C20H27NO. Calculated, %:
C 80.76; H 9.15; N 4.71.
N-(8-Methyl-1,3-dihydronaphtho[1,2-c]furan-4-yl)methylpyrrolidine (4d). Yield 1.80 g (66%); bp
200-201ºC (1-2 mm Hg); mp picrate 189-192ºC (EtOH). IR spectrum, , cm-1: 780, 805, 870, 1130, 1500, 1600,
1
3040. H NMR spectrum, , ppm (J, Hz): 7.71 (1H, d, J = 8.3, H-6); 7.55 (1H, s, H-5); 7.31 (1H, d, J = 1.8,
H-9); 7.25 (1H, dd, J1 = 8.3, J2 = 1.8, H-7); 5.35 (2H, t, J = 3.1, H-3); 5.21 (2H, t, J = 3.1, H-1); 3.66 (2H, s,
4-CH2); 2.51 (3H, s, 8-CH3); 2.48 (4H, m, -CH2 pyrrolidine); 1.77 (4H, m, -CH2 pyrrolidine). Found, %:
C 81.27; H 8.14; N 5.39. C18H21NO. Calculated, %: C 80.86; H 7.92; N 5.24.
N-(8-Methyl-1,3-dihydronaphtho[1,2-c]furan-4-yl)methylpiperidine (4e). Yield 1.91 g (68%); bp
209-210ºC (1-2 mm Hg); mp 65-66ºC (ether–dichloromethane), mp picrate 194-195ºC (EtOH), mp
hydrochloride 244-245ºC (abs. EtOH). IR spectrum, , cm-1: 720, 770, 790, 870, 1010, 1030, 1130, 1580, 3030.
1H NMR spectrum, , ppm (J, Hz): 7.69 (1H, d, J = 8.4, H-6); 7.50 (1H, s, H-5); 7.30 (1H, d, J = 1.8, H-9); 7.24
(1H, dd, J1 = 8.4, J2 = 1.8, H-7); 5.34 (2H, t, J = 3.1, H-3); 5.22 (2H, t, J = 3.1, H-1); 3.49 (2H, s, 4-CH2); 2.51
(3H, s, 8-CH3); 2.36 (4H, m, -CH2 piperidine); 1.55 (4H, m, -CH2 piperidine); 1.44 (2H, m, CH2 -piperidine).
13C NMR spectrum, , ppm: 136.00, 134.71, 133.66, 130.84, 130.71, 129.93, 127.41, 127.02, 126.25 and 122.17
(C arom.), 73.46 and 72.23 (C-1 and C-3); 61.84 (4-CH2); 53.92 (C- piperidine); 25.51 (C- piperidine); 23.90
(C- piperidine); 21.20 (8-CH3). Found, %: C 81.53; H 8.47; N 5.22. C19H23NO. Calculated, %: C 81.14; H 8.24;
N 4.98.
N-(8-Methyl-1,3-dihydronaphtho[1,2-c]furan-4-yl)methylmorpholine (4f). Yield 1.98 g (70%); mp
117-118ºC (ether–dichloromethane), mp picrate 107-108ºC (EtOH), mp hydrochloride 175-176ºC (abs. EtOH).
1
IR spectrum, , cm-1: 730, 760, 870, 1010, 1060, 1570, 1600, 3030. H NMR spectrum, , ppm (J, Hz): 7.71
(1H, d, J = 8.3, H-6); 7.53 (1H, s, H-5); 7.32 (1H, d, J = 1.9, H-9); 7.26 (1H, dd, J1 = 8.3, J2 = 1.9, H-7); 5.35
(2H, t, J = 3.0, H-3); 5.24 (2H, t, J = 3.0, H-1); 3.60 (4H, m, OCH2 morpholine); 3.55 (2H, s, 4-CH2); 2.52 (3H,
d, 8-CH3); 2.40 (4H, m, NCH2 morpholine). 13C NMR spectrum, , ppm: 135.91, 134.98, 133.84, 130.66,
128.84, 127.44, 127.15, 126.62, 126.49 and 122.19 (C arom.), 73.42 and 72.26 (C-1 and C-3); 66.01 (OCH2
morpholino); 61.41 (4-CH2); 53.03 (NCH2 morpholine); 21.19 (8-CH3). Found, %: C 76.72; H 7.69; N 5.19.
C18H21NO2. Calculated, %: C 76.33; H 7.47; N 4.94.
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