A new intramolecular recyclization in water-base cleavage reaction of 2,2-dialkyl-4-hydroxymethylbenz[f]iso indolinium bromides and chlorides

Article abstract of DOI:10.1002/jhet.5570400614

The water-base cleavage reaction of 2,2-dialkyl-4-hydroxymethylbenz[f]isoindolinium bromides and chlorides (2b-g) and (4a-g) was investigated. It was established that the above-mentioned salts in water-base cleavage reaction undergo intramolecular recyclization. As a result 1,3-dihydro-4-dialkylaminomethyl-naphto[1,2-c]furans (5a-g) are obtained in 62-72% yields. The same products in 65-70% yields may be obtained by step cyclization cleavage reaction of dialkyl-4-hydroxybutyn-2-yl-(3-phenylpropargyl) ammonium salts (1b-g) and (3a-g), as well. The structure of the resulting amines 5a-g are determined and approved by X-ray diffraction, nmr and ir spectroscopic methods.

Full text of DOI:10.1002/jhet.5570400614

Nov-Dec 2003
1059
A new intramolecular recyclization in water-base cleavage
reaction of 2,2-dialkyl-4-hydroxymethylbenz[f]iso
indolinium bromides and chlorides
a
a
a
Emma O. Chukhajian , Hasmik R. Gevorkyan , Eliza O. Chukhajian ,
a
b
b
Knarik G. Shahkhatuni , Henrik A. Panosyan , Rafael A.Tamazyan
a
Institute of Organic Chemistry of National Academy of Sciences of the Republic of Armenia, Yerevan
375091
b
Molecule Structure Research Center of National Academy of Sciences of the Republic of Armenia, Yerevan
375014
Received October 17, 2002
The water-base cleavage reaction of 2,2-dialkyl-4-hydroxymethylbenz[f]isoindolinium bromides and
chlorides (2b-g) and (4a-g) was investigated. It was established that the above-mentioned salts in water-base
cleavage reaction undergo intramolecular recyclization. As a result 1,3-dihydro-4-dialkylaminomethyl-
naphto[1,2-c]furans (5a-g) are obtained in 62-72% yields. The same products in 65-70% yields may be
obtained by step cyclization cleavage reaction of dialkyl-4-hydroxybutyn-2-yl-(3-phenylpropargyl) ammo-
nium salts (1b-g) and (3a-g), as well. The structure of the resulting amines 5a-g are determined and
approved by X-ray diffraction, nmr and ir spectroscopic methods.
J. Heterocyclic Chem., 40, 1059 (2003).
Introduction.
There are many publications and reviews in literature
devoted to the issue of recyclization of carbo- and hetero-
cyclic systems [1-6]. In this direction there are reactions of
Yurev, Hafner, rearrangements of Dimrot, Boulton-
Katritzky, Cornforth, Kost-Sagittulin, etc. In review of V.
P. Litvinov [1] recyclization reactions of carbo- and hete-
rocycles with malononitrile participation and recyclization
of compounds containing a malononitrile fragment are dis-
cussed. In particular in this review the recyclization of
three-, four-, five- and six-membered cycles are described.
In all cases under the influence of various reagents (nucle-
ophilic, electrophilic or dipolar) ring opening is the first
step in the reaction. During recyclization, formation of a
new ring is in most cases accompanied by implantation or
replacement of a heteroatom, and enlargement or reduction
of the ring. The recyclization reactions described in the lit-
erature relate to intermolecular recyclization. There is only
one example of the purely intramolecular recyclization
where the recyclization is caused by thermal treatment [7].
In this paper we describe a new intramolecular recy-
clization reaction of 2,2-dialkyl-4-hydroxymethylbenz[f]-
isoindolinium salts (2b-g) and (4a-g) under water-base
cleavage conditions.
Previously we reported, that 2,2-dialkylisoindolinium
and -benz[f]isoindolinium salts in conditions of water-base
cleavage reaction, with loss of an alkene, transform to
2-alkylisoindolines and –benz[f]isoindolines (Scheme 1).
This reaction takes place if at least one of the alkyl
groups connected with nitrogen atom can undergo
β-elimination [8].
We were interested in studying the behavior of 2,2-
dialkyl-4-hydroxymethylbenz[f]isoindolinium bromides
and chlorides (2b-g) and (4a-g) under water-base cleavage
reaction conditions. The salts were synthesized in 75-85%
yields by intramolecular cyclization of dialkyl-4-hydroxy-
butyn-2-yl-(3-phenylpropargyl) ammonium bromides and
chlorides (1b-g) and (3a-g) under base-catalyzed condi-
tions (Scheme 2) [9].
At first we investigated the water-base cleavage reaction
of 2,2-diethyl-4-hydroxymethylbenz[f]isoindolinium bro-
mide (2b). Surprisingly the nmr spectra of the resulting com-
pound did not confirm the expected structure of 2-ethyl-4-
hydroxymethylbenz[f]isoindoline. To determine the structure
of resulting amine an X-ray diffraction experiment the bro-
momethylate of this amine was carried out (detailed experi-
mental data is given in table 1). The structure was determined
by direct methods using the crystallographic programs
SHELXL-93. The positional parameters of hydrogen atoms
were found from geometrical calculations. In the final refine-
ment positional, anisotropic and thermal parameters for all

1060
E. O. Chukhajian, H. R. Gevorkyan, E. O. Chukhajian, K. G. Shahkhatuni,
H. A. Panosyan, R. A.Tamazyan
Vol. 40
Table 1
Table 3
Main Interatomic Distances in the Molecule
X-ray Experimental Data
Atom1 Atom2 Distance
Atom1 Atom2 Distance
a
13.474 (3)
b
c
α
β
γ
V
Z
ρ
9.052 (2)
15.013 (3)
90.00
108.57(3)
90.00
1735.6 (6)
4
1.406
C1
C1
C2
C3
C4
C5
C5
C6
C7
C7
C8
C2
C6
C3
C4
C5
C13
C6
C7
C11
C8
O9
1.355 (9)
1.421 (8)
1.396 (10)
1.366 (10)
1.422 (9)
1.405 (8)
1.407 (8)
1.417 (8)
1.368 (7)
1.490 (8)
1.416 (7)
O9
C10
C11
C12
C13
C14
N15
C17
C19
C16
C18
C20
1.430 (7)
1.504 (8)
1.406 (7)
1.381 (8)
1.511 (7)
1.536 (7)
1.479 (9)
1.506 (7)
1.580 (9)
1.393 (11)
1.530 (9)
C10
C11
C12
C12
C14
N15
N15
N15
C17
C19
exp
radiation
monochromator
N
ϑ
MoKα λ=0.71073
Graphite 002
1810
measured
ref
25.84
max
N
N
∆ρ
∆ρ
R
observed I>σ (I)
1725
203
0.691
-0.291
0.0502
1.027
ref
param
Table 4
Bonding Angles in Molecule
max
min
Atom1 Atom2 Atom3 Angle
Atom1 Atom2 Atom3 Angle
S
C2
C1
C4
C3
C13
C13
C6
C5
C5
C1
C2
C3
C4
C5
C5
C5
C6
C6
C6
C7
C7
C7
C8
O9
C10
C6
C3
C2
C5
C6
C4
C4
C7
C1
C1
C6
C8
C8
C7
C10
C11
111.9 (6)
121.0 (6)
120.3 (7)
120.9 (7)
119.9 (5)
122.2 (6)
117.9 (5)
116.8 (5)
120.0 (6)
123.2 (5)
122.2 (5)
109.7 (5)
128.0 (5)
105.8 (5)
110.4 (5)
105.5 (5)
C7
C7
C11
C11
C11
C12
C12
C12
C13
C14
N15
N15
N15
N15
N15
N15
C17
C19
C12
C10
C10
C11
C14
C14
C5
N15
C19
C14
C14
C16
C16
C16
N15
C20
121.2 (5)
108.1 (5)
130.7 (5)
117.2 (5)
118.7 (5)
123.9 (5)
122.5 (5)
115.1 (4)
113.1 (5)
113.2 (5)
106.3 (4)
107.5 (6)
108.2 (5)
108.4 (5)
113.6 (7)
114.2 (5)
Table 2
The Fractional Coordinates of Basic Atoms in the Crystal
C12
C13
C13
C11
C12
C12
C17
C17
C19
C17
C19
C14
C18
N15
Atom
X/a
Y/b
Z/c
U
eq
Br1
O1
C1
C2
C3
C4
C5
C6
C7
0.62084 (5)
0.6267 (10)
0.8316 (5)
0.8162 (5)
0.9005 (6)
1.0004 (6)
1.0208 (5)
0.9347 (4)
0.9569 (4)
0.8812 (5)
0.9425 (3)
1.0515 (5)
1.0570 (4)
1.1433 (4)
1.1226 (4)
1.2551 (4)
1.3173 (4)
1.2707 (6)
1.3110 (6)
1.3654 (7)
1.4277 (5)
1.5030 (6)
0.83046 (8)
0.0752 (10)
0.7834 (7)
0.6865 (8)
0.6297 (8)
0.6730 (8)
0.7743 (7)
0.8299 (6)
0.9334 (6)
1.0192 (8)
1.1183 (5)
1.0877 (7)
0.9748 (6)
0.9179 (6)
0.8220 (7)
0.9649 (7)
0.8651 (6)
0.8834 (11)
0.7067 (8)
0.6704 (10)
0.9236 (8)
0.8365 (10)
0.64915 (5)
0.4787 (6)
0.4985 (5)
0.4265 (5)
0.4023 (5)
0.4502 (5)
0.5262 (4)
0.5497 (4)
0.6242 (4)
0.6576 (4)
0.7261 (3)
0.7455 (4)
0.6736 (4)
0.6514 (4)
0.5761 (4)
0.6997 (4)
0.7811 (3)
0.8646 (6)
0.7558 (7)
0.6939 (7)
0.8131 (5)
0.8941 (6)
0.0597 (3)
0.083 (2)
0.050 (2)
0.056 (2)
0.064 (2)
C7
C11
C11
C6
O9
C8
0.058 (2)
0.0392 (14)
0.0366 (13)
0.0360 (13)
0.051 (2)
0.0610 (13)
0.048 (2)
0.0348 (13)
0.0351 (14)
0.0409 (14)
0.0397 (14)
0.0467 (13)
0.094 (3)
C8
O9
O9
C10
C11
C12
C13
C14
N15
C16
C17
C18
C19
C20
results in 1,3-dihydro-4-diethylaminomethylnaphto[1,2-c]-
furan (5b) instead of the expected 2-ethyl-4-hydroxymethyl-
benz[f]isoindoline.
In order to state the general nature of the discovered recy-
clization we have studied the behaviour of 2c-g and 4a-g salts
in water-base cleavage conditions. It turned out, that these
salts smoothly undergo the intramolecular recyclization too,
forming 1,3-dihydro-4-dialkylaminomethylnaphto[1,2-
c]furans (5a-g) in 62-72% yields. The data obtained show that
the discovered recyclization reaction is general. It should be
noted, that the amines 5a-g obtained in the cyclization reac-
tion of salts 1b-g and 3a-g combined with that obtained in the
subsequent cleavage reaction of cyclic salts 2b-g and 4a-g,
give amines 5a-g in 65-70% yields (Scheme 2).
Comparing the results of the reactions given in Scheme 1
with those in Scheme 2, shows that the hydroxymethyl
group of 2b-g and 4a-g plays the role of base in this recy-
clization reaction. In water-base medium the hydrox-
ymethyl group is deprotonated to give the alkoxy anion
shown in Scheme 2. The positive charge on the nitrogen
atom induces a partial positive charge on the neighboring
0.073 (2)
0.090 (3)
0.054 (2)
0.093 (3)
nonhydrogen atoms and the constrained positional and
isotropic thermal parameters of hydrogen atoms were refined
by the full-matrix least-squares procedure. The final values
of positional and equivalent thermal parameters of nonhy-
drogen atoms are given in the table 2. The main interatomic
distances and angles are given in Tables 3 and 4 respectively.
The structure of molecule is represented in the Figure 1. The
results of the structural investigation allow for the explana-
tion of the nmr spectra and show that for salt 2b a new
intramolecular recyclization takes place, due to breaking of
the isoindoline ring and formation of the dihydrofuranic ring
(Scheme 2). In other words the water-cleavage reaction

Nov-Dec 2003
A new intramolecular recyclization in water-base cleavage reaction
1061
refluxed during 2-3 hours at 90-92°, then extracted by ether
(2x40 mL). The ethereal extract is washed with water and dried
over magnesium sulfate. After removing ether the remaining
amines 5a-g are distilled.
General Procedure of Step Cyclization-cleavage Reaction of
Dialkyl-4-hydroxybutyn-2-yl-(3-phenylpropargyl) Ammonium
Bromides and Chlorides (1b-g) and (3a-g).
To a solution of 11-20 mmole of salts 1b-g and 3a-g in 5-6 mL
water 1.1-2.0 mL 2 N potassium hydroxide (mole-ratio
salt/base=5/1) is added. After cyclization the reaction mixture is
extracted by ether (2x20 mL). Ethereal extract is acidified by
hydrochloric acid. The hydrochloride layer is separated from the
ethereal layer. By alkalization of the hydrochloride layer and
extracting by ether (2x25 mL) a first crop of amines 5a-g are sep-
arated with 8-10% yields (mixed melting points of their picrates
show these compounds to be identical with those obtained from
salts 2b-g and 4a-g). After that a two-fold molar quantity of
potassium hydroxide is added to the reaction mixture (promoting
the water-base cleavage reaction of cyclic salts 2b-g and 4a-g).
The reaction mixture is again extracted with ether, the ether layer
acidified with hydrochloric acid then separated. The resulting
hydrochloride layer is then made alkaline and extracted with
ether (as described above) to give amines 5a-g. After purification
by vacuum distillation amines 5a and 5e crystallized by staying
at room temperature.
Figure 1. The molecular structure of brommethylate of amine 5b.
carbon making it susceptible to intramolecular nucleophile
attack of alkoxy anion. This leads to breaking of the iso-
indolinium N-C bond, as well as to formation of a new O-C
bond, resulting in dihydrofurane ring formation (Scheme 2).
Unlike the recyclization reactions described in the litera-
ture, in the intramolecular recyclization reaction discov-
ered by us the initial ring opening takes place due to nucle-
ophile attack of the alkoxy anion in the molecule. Hence,
the ring does not change size rather a five-membered
isoindoline ring is replaced by dihydrofurane.
1,3-Dihydro-4-dimethylaminomethylnaphto[1,2-c]furan (5a).
Amine 5a was obtained in 68% yield (2.31 g, 10 mmole) by
water-base cleavage reaction of the salt 4a (3.95 g, 15 mmole)
20
with bp 180°/3 mm Hg, mp 40°; n = 1.5989; ir: 750 (o-substi-
d
In the ir spectra of amines 5a-g characteristic zones of
absorption are presented respectively: for di- and penta-
tuted benzene ring), 860 (pentasubstituted benzene ring), 1050,
-1
1100 (C–O in cycle), 1510, 1600 and 3060 (aromatic ring) cm ;
-1
substituted benzene rings - 750 and 870 cm , for aromatic
1
H nmr (DMSO-d /CCl – 1/3): δ 7.83 (m, 1H, 6- or 9-H), 7.60
6
4
ring - 1500, 1600, 3060 and for cyclic ethereal group -
(s, 1H, 5-H), 7.56 (m, 1H, 9- or 6-H), 7.44 (m, 2H, 7-, 8-H), 5.39
(t, 2H, OCH , J=3.0 Hz), 5.23 (t, 2H, OCH , J=3.0 Hz), 3.49 (s,
-1
1050, 1100 cm .
2
2
13
Structures of amines 5a-e and amines 5f, 5g hydrochlo-
2H, NCH ), 2.23 (s, 6H, CH ); C nmr (DMSO-d /CCl – 1/3):
2 3 6 4
1
δ
135.9, 134.3, 132.5, 127.6, 126.5(2C), 126.3, 125.5, 124.9,
ride were established by H nmr spectroscopy and the
123.1, 73.4, 72.3, 62.2, 44.8(2C); mp 155° of 5a picrate (ethyl
alcohol); mp 201° of 5a hydrochloride (absolute ethyl alcohol).
structures of amines 5a, 5c, 5d, and amine 5g hydrochlo-
13
ride were supported by C nmr, DEPT, HETCOR.
Anal. Calcd. for C
H NO: C, 79.30; H, 7.49; N, 6.17. Found:
15 17
Composition of amines 5a-g was consistent with the
results of elemental analysis.
C, 79.61; H, 7.69; N, 6.42.
1,3-Dihydro-4-diethylaminomethylnaphto[1,2-c]furan (5b).
Amine 5b was obtained in 70% yield (2.6 g, 10.43 mmole) by
water-base cleavage reaction of the salt 2b (5.04 g, 15 mmole) or
EXPERIMENTAL
20
4b (4.38 g, 15 mmole) with bp 165°/3 mm Hg; n = 1.5850; ir:
The initial salts 1b-g and 3a-g were prepared in laboratory
conditions. The ir spectra were recorded on an IR-20 spectrome-
ter. Samples were prepared as potassium bromide tablets or in
Vaseline oil. The nmr spectra were carried out on a “Varian
Mercury 300” spectrometer at 300.08 MHz for H and 75.46
MHz for C at temperature of 303 K using TMS as an internal
d
730 (o-substituted benzene ring), 870 (pentasubstituted benzene
ring), 1050, 1110 (C–O in cycle), 1500, 1580 and 3050 (aromatic
-1
1
ring) cm ; H nmr (DMSO-d /CCl – 1/3): δ 7.92 (m, 1H, 6- or
6
4
1
9-H), 7.73 (s, 1H, 5-H), 7.67 (m, 1H, 9- or 6-H), 7.50 (m, 2H, 7-,
8-H), 5.41 (t, 2H, OCH , J=3.0 Hz), 5.32 (t, 2H, OCH , J=3.0
13
2
2
Hz), 3.67 (s, 2H, NCH ), 2.52 (q, 4H, CH , J=7.0 Hz); 1.04 (t,
standard. The X-ray diffraction measurements were performed
on a CAD-4 “Enraf-Nonius” diffractometer.
2
2
6H, CH , J=7.0 Hz); mp 168-170° of 5b picrate (ethyl alcohol);
3
mp 184-185° of 5b hydrochloride (absolute ethyl alcohol).
General Procedure for the Water-base Cleavage Reaction of 2,2-
Dialkyl-4-hydroxymethylbenz[f]isoindolinium Bromides and
Chlorides (2b-g) and (4a-g).
Anal. Calcd. for C
H NO: C, 80.00; H, 8.23; N, 5.49. Found:
17 21
C, 80.30; H, 8.43; N, 5.78.
1,3-Dihydro-4-dipropylaminomethylnaphto[1,2-c]furan (5c).
To a solution of 11-20 mmole of initial salts 2b-g and 4a-g in
5-7 mL of water a two-fold molar quantity of potassium hydrox-
ide dissolved in 3-4 mL of water is added. The reaction mixture is
Amine 5c was obtained in 62% yield (3.4 g, 12 mmole) by
water-base cleavage reaction of the salt 2c (7.28 g, 20 mmole) or

1062
E. O. Chukhajian, H. R. Gevorkyan, E. O. Chukhajian, K. G. Shahkhatuni,
H. A. Panosyan, R. A.Tamazyan
Vol. 40
20
CH ); mp 163° of 5f picrate (ethyl alcohol); mp 204-205° of 5f
4c (6.39 g, 20 mmole) with bp 185°/3 mm Hg; n = 1.5710; ir:
2
d
hydrochloride (absolute ethyl alcohol).
760 (o-substituted benzene ring), 840 (pentasubstituted benzene
ring), 1060, 1110 (C–O in cycle), 1510, 1600 and 3060 (aromatic
Anal. Calcd. for C H NO: C, 80.90; H, 7.86; N, 5.24. Found:
C, 81.32; H, 8.05; N, 5.56.
18 21
-1
1
ring) cm ; H nmr (DMSO-d /CCl – 1/3): δ 7.82 (m, 1H, 6- or
6
4
9-H), 7.60 (s, 1H, 5-H), 7.56 (m, 1H, 9- or 6-H), 7.43 (m, 2H, 7-,
8-H), 5.38 (t, 2H, OCH , J=3.0 Hz), 5.24 (t, 2H, OCH , J=3.0
4-(1,3-Dihydro-naphtho[1,2-c]furan-4-ylmethyl)-morpholine
(5g).
2
2
Hz), 3.61 (s, 2H, NCH ), 2.37 (t, 4H, CH N, J=7.5 Hz), 1.49 (tq,
2
2
13
Amine 5g was obtained in 71% yield (2.1 g, 7.8 mmole) by
water-base cleavage reaction of the salt 2g (3.85 g, 11 mmole) or
4g (3.36 g, 11 mmole) bp 189°/3 mm Hg; ir: 750 (o-substituted
benzene ring), 870 (pentasubstituted benzene ring), 1060, 1110
4H, CH , J=7.5, 7.2 Hz), 0.86 (t, 6H, CH , J=7.2 Hz); C nmr
2
3
(DMSO-d /CCl – 1/3): δ 135.8, 134.3, 132.6, 131.9, 127.5,
6
4
126.4, 126.2, 125.3, 124.8, 123.1, 73.5, 72.3, 57.6, 55.4(2C),
19.5(2C), 11,5(2C); mp 159° of 5c picrate (ethyl alcohol); mp
155-156° of 5c hydrochloride (absolute ethyl alcohol).
-1
1
(C–O in cycle), 1510, 1600 and 3050 (aromatic ring) cm ; H
nmr of amine 5g hydrochloride (DMSO-d /CCl – 1/3): δ 12.40
Anal. Calcd. for C
H NO: C, 80.56; H, 8.83; N, 4.95. Found:
6
4
19 25
(br, 1H, hydrochloride proton), 8.43 (br, 1H, 5-H), 7.98 (dd, 1H,
6- or 9-H, J=7.2, 1.8 Hz), 7.50-7.64 (m, 3H, 7-, 8-, 9- or 6-H),
C, 80.93; H, 9.04; N, 5.23.
1,3-Dihydro-4-dibutylaminomethylnaphto[1,2-c]furan (5d).
Amine 5d was obtained in 66% yield (4.1 g, 13.2 mmole) by
5.43 (s, 4H, OCH ), 4.37 (br, 2H, NCH ), 4.07 (br, 2H, CH ),
2
2
2
13
3.88 (br, 2H, CH ), 3.21 (br, 4H, CH ); C nmr of amine 5g
2
2
water-base cleavage reaction of the salt 2d (7.84 g, 20 mmole) or
hydrochloride (DMSO-d /CCl – 1/3): δ 136.8, 134.9, 132.3,
6 4
20
4d (6.95 g, 20 mmole) bp 200-202°/3 mm Hg; n = 1.5603; ir:
131.9, 128.5, 127.1, 126.9, 125.6, 123.4, 120.8, 73.6, 72.9,
62.7(2C), 56.3, 50.5(2C); mp 155-156° of 5g picrate (ethyl alco-
hol); mp 194-195° of 5g hydrochloride (absolute ethyl alcohol).
d
760 (o-substituted benzene ring), 850 (pentasubstituted benzene
ring), 1050, 1100 (C–O in cycle), 1520, 1600 and 3080 (aromatic
-1
1
ring) cm ; H nmr (DMSO-d /CCl – 1/3): δ 7.82 (m, 1H, 6- or
Anal. Calcd. for C H NO : C, 75.84; H, 7.06; N, 5.20.
6
4
17 19 2
9-H), 7.59 (s, 1H, 5-H), 7.56 (m, 1H, 9- or 6-H), 7.43 (m, 2H, 7-,
8-H), 5.38 (t, 2H, OCH , J=3.0 Hz), 5.23 (t, 2H, OCH , J=3.0
Found: C, 76.18; H, 7.25; N, 5.48.
2
2
1-(4-Hydroxy-but-2-ynyl)-1-(3-phenyl-prop-2-ynyl)-pyrroli-
dinium Chloride (3e).
Hz), 3.60 (s, 2H, NCH ), 2.39 (t, 4H, CH N, J=7.2 Hz), 1.44 (m,
2
2
13
4H, CH ), 1.28 (m, 4H, CH ), 0.87 (t, 6H, CH , J=7.2 Hz);
C
2
2
3
This compound was obtained in 95% yield, mp 92°; ir:
700, 750 (monosubstituted benzene ring), 1020, (C–O in
C–OH), 1500, 1560, 1600 and 3060 (aromatic ring), 3200-3350
nmr (DMSO-d /CCl – 1/3): δ 135.8, 134.3, 132.5, 131.9, 127.5,
6
4
126.4, 126.2, 125.3, 124.8, 123.1, 73.4, 72.3, 57.6, 52.9(2C),
28.5(2C), 19.9(2C), 13,5(2C); mp 100° of 5d picrate (ethyl alco-
hol); mp 120° of 5d hydrochloride (absolute ethyl alcohol).
-1
1
(O–H) cm , H nmr (DMSO-d /CCl – 1/3): δ 7.58 (m, 2H,
6
4
ortho-phenyl protons), 7.40 (m, 3H, meta- and para-phenyl pro-
Anal. Calcd. for C
C, 81.38; H, 9.57; N, 4.78.
H NO: C, 81.03; H, 9.32; N, 4.50. Found:
21 29
tons), 5.26 (br, 1H, OH), 4.91 (s, 2H, NCH ), 4.72 (t, 2H, NCH ,
2
2
J=2.0 Hz), 4.19 (br, 2H, OCH ), 3.88 (t, 4H, CH N, J=7.2, Hz),
2
2
1-(1,3-Dihydro-naphtho[1,2-c]furan-4-ylmethyl)-pyrrolidine
(5e).
2.28 (m, 4H, CH ).
2
Anal. Calcd. for C
H ClNO: C, 70.46; H, 6.96; N, 4.83.
17 20
Found: C, 70.85; H, 7.15; N, 5.13.
Amine 5e was obtained in 70% yield (2.48 g, 9.8 mmole) by
water-base cleavage reaction of the salt 2e (4.67 g, 14 mmole) or
4e (4.1 g, 14 mmole) bp 198°/1 mm Hg, mp 43°; ir: 760 (o-sub-
stituted benzene ring), 870 (pentasubstituted benzene ring), 1050,
2,2-Tetramethylen-4-hydroxymethylbenz[f]isoindolinium
Chloride (4e).
-1
This compound was obtained in 75% yield, mp 231-232°; ir:
730, 760 (o-substituted benzene ring), 860 (pentasubstituted ben-
zene ring), 1050 (C–O in C–OH), 1500, 1550, 1600 and 3030
1110 (C–O in cycle), 1500, 1580 and 3050 (aromatic ring) cm ;
1
H nmr (DMSO-d /CCl – 1/3): δ 7.95 (m, 1H, 6- or 9-H), 7.73
6
4
(s, 1H, 5-H), 7.65 (m, 1H, 9- or 6-H), 7.50 (m, 2H, 7-, 8-H), 5.40
(t, 2H, OCH , J=3.2 Hz), 5.24 (t, 2H, OCH , J=3.2 Hz), 3.68 (s
-1
1
(aromatic ring), 3300-3400 (O–H) cm , H nmr (DMSO-d
6
2
2
/CCl – 1/3): δ 8.14 (d, 1H, 8-H, J=8.1, Hz), 7.90 (dd, 1H, 5-H,
2H, NCH ), 2.45 (m, 4H, CH N); 1.70 (m, 4H, CH ); mp 150° of
4
2
2
2
J=7.2, 2.2 Hz), 7.81 (s, 1H, 9-H), 7.53 (m, 2H, 6-, 7-H), 5.82 (br,
1H, OH), 5.35 (s, 2H, 3-H), 5.09 (s, 2H, 1-H), 4.97 (s, 2H, 4-H),
5e picrate (ethyl alcohol); mp 165-168° of 5d hydrochloride
(absolute ethyl alcohol).
13
3.81 (m, 4H, CH N), 2.28 (m, 4H, 2CH ); C nmr (DMSO-
Anal. Calcd for C
H NO: C, 80.63; H, 7.51; N, 5.53. Found:
2
2
17 19
d /CCl – 1/3): δ 133.2, 133.0, 131.6, 130.8, 129.9, 128.2, 126.1,
C, 81.03; H, 7.72; N, 5.83.
6
4
125.8, 123.9, 121.2, 66.1, 65.4, 62.5(2C), 58.2, 21.4(2C).
Anal. Calcd. for C ClNO: C, 70.46; H, 6.96; N, 4.83.
1-(1,3-Dihydro-naphtho[1,2-c]furan-4-ylmethyl)-piperidine (5f).
H
17 20
Found: C, 70.86; H, 7.14; N, 5.13.
Amine 5f was obtained in 72% yield (2.48 g, 9.3 mmole) by
water-base cleavage reaction of the salt 2f (4.52 g, 13 mmole) or
4f (4.0 g, 1.3 mmole) mp 55° (hexane); ir: 740, 760 (o-substituted
benzene ring), 870 (pentasubstituted benzene ring), 1050, 1110
REFERENCES AND NOTES
-1
1
(C–O in cycle), 1500, 1600 and 3050 (aromatic ring) cm ; H
nmr hydrochloride of amine 5f (DMSO-d /CCl – 1/3): δ 12.14
[1] V. P. Litvinov, Russ. Chem. Rev., 68, 39 (1999).
[2] E. V. Babaev, A. V. Efimov, D. A. Maiboroda and K. Jug. Eur.
J. Org. Chem., 193 (1998).
6
4
(br, 1H, hydrochloride proton), 8.54 (s, 1H, 5-H), 8.01 (d, 1H, 6-
or 9-H, J=8.0 Hz), 7.52-7.60 (m, 3H, 7-, 8-, 9- or 6-H), 5.45 (t,
2H, OCH , J=3.0 Hz), 5.39 (t, 2H, OCH , J=3.0 Hz), 4.27 (d, 2H,
[3]
Perkin Trans. 1, 10, 1333 (1999).
[4] H. Heaney and M. O. Taha, ARKIVOC, Vol 1, Part 3, 343
(2000).
D. Loakes, D M. Brown and S. A. Salisbury, J. Chem. Soc.,
2
2
NCH , J=5.4 Hz), 3.38 (d, 2H, CH N, J=11.0 Hz), 2.95 (m, 2H,
2
2
CH N), 2.19 (m, 2H, CH ), 1.80 (m, 3H, CH ), 1.46 (m, 1H,
2
2
2

Nov-Dec 2003
A new intramolecular recyclization in water-base cleavage reaction
1063
[5]
G. G. Danagulyan and L. G. Sahakyan, Khim. Geterotsikl.
O. Kappe (Eds) (1998).
Soedin. (in Russian), Riga, 5, 698 (2000); Chem. Het. Com., 36, 5, 613 (2000).
[8]
Riga, 4, 433 (1993); Chem. Abstr., 119/270919t (1993).
[9] E. O. Chukhajian, El. O. Chukhajian, H. R. Gevorkyan, K. G.
Shahkhatuni, F. S. Kinoyan and H A. Panosyan, Khim. Geterotsikl.
Soedin. (in Russian), Riga, in the press.
E. O. Chukhajian, Khim. Geterotsikl. Soedin. (in Russian),
[6]
Sakach and K. Renovgashi, J. Serb. Chem. Soc., 66, 23 (2001).
[7] W. M. F. Fabian and G. Kollenz, Proceedings of ECHET98,
The Electronic Conference on Heterocyclic Chemistry’98 H. S. Rzepa, C.
S. Stojanovich, D. M. Gabor, L. Medich-Mijachevich, M.