Specific features of the chemical behavior of acetylenic derivatives of benzocrown ethers

Article abstract of DOI:10.1023/A:1011367311643

4′-Ethynylbenzo-12-crown-4 (8), 4′-ethynylbenzo-15-crown-5 (9), and 4′-ethynylbenzo-18-crown-6 (10) were synthesized by cross-coupling of the corresponding aryl iodides 1-3 with 2-methylbut-3-yn-2-ol (4a) followed by the retro-Favorsky cleavage of the res

Full text of DOI:10.1023/A:1011367311643

868
Russian Chemical Bulletin, International Edition, Vol. 50, No. 5, pp. 868—873, May, 2001
Specific features of the chemical behavior of acetylenic derivatives
of benzocrown ethers
S. V. Klyatskaya, E. V. Tretyakov, and S. F. Vasilevsky«
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 2350. E-mail: vasilev@ns.kinetics.nsc.ru
4´-Ethynylbenzo-12-crown-4 (8), 4´-ethynylbenzo-15-crown-5 (9), and 4´-ethynylben-
zo-18-crown-6 (10) were synthesized by cross-coupling of the corresponding aryl iodides 1—3
with 2-methylbut-3-yn-2-ol (4a) followed by the retro-Favorsky cleavage of the resulting
carbinols. Unlike the corresponding benzo-12-crown-4 derivative (5a), the cleavage of tertiary
acetylenic alcohols of benzo-15-crown-5 (6a) and benzo-18-crown-6 (7a) requires more than
one molar equivalent of KOH. Aminoalkylation of crown ether 8 gives Mannich bases,
independently of the reaction conditions and the nature of amine. The aminomethylation of
acetylenic crown ethers 9 and 10 with paraform—piperidine (morpholine) in the presence of
CuCl yields 1,4-disubstituted buta-1,3-diynes (19, 20) rather than Mannich bases.
Key words: benzocrown ethers, alkynes, the retro-Favorsky reaction, the Mannich
reaction, Frank—Meister—Hay modification, crown effect.
The discovery of crown compounds capable of bind-
The goal of the present work is to synthesize
ethynylcrown ethers and study their chemical transfor-
mations.9,10
ing certain ions with high selectivity has exerted a great
effect on organic chemistry and on the development of
new technological processes.1 This can be illustrated
with the comparatively recent data on the use of unsat-
urated benzocrown ethers in modern technology (com-
ponents of liquid-crystal formulations, nonlinear optics,
catalysts, etc.).2—5
From this point of view, introduction of an acety-
lenic fragment into the crown ether molecule can give
rise to a new promising intermediate product. The
mutual influence of the crown ether ring and the acety-
lenic substituents in its molecule makes it possible to
use this compound for preparative and applied purposes.
Thus, even in the first study concerning acetylenic
derivatives of crown ethers, they were used to obtain
long-chain crown ethers and other unique compounds.6
Nevertheless, the chemistry of acetylenic derivatives
of crown ethers remains poorly investigated so far. Only
a few published papers are devoted to the synthesis of
alkynylbenzocrown ethers by cross-coupling of aryl io-
dides with terminal acetylene derivatives,7,8 whereas the
preparation of ethynylbenzocrown ethers are not de-
scribed at all.
Results and Discussion
Synthesis of 4-(RC≡C)-benzocrown ethers. Termi-
nal arylacetylene derivatives can be obtained by alkaline
cleavage of tertiary arylacetylenic alcohols according to
the retro-Favorsky reaction (Scheme 1),11 which is
usually carried out in anhydrous benzene at 75—80 °C
and catalyzed by calcined KOH.
Tertiary acetylenic alcohols 6a and 7a are cleaved
neither under the above conditions used earlier in the
synthesis of some aryl- and hetarylacetylenes12 nor in
boiling toluene. This transformation was successful only
in the presence of more than one molar equivalent of
alkali, suggesting that the potassium cation plays an
important part in the cleavage of tertiary arylacetylenic
alcohol.
According to the literature data,11,13 the cleavage of
carbinolates includes proton transfer from the alkyl group
of the dialkylcarbinol fragment. On the other hand, when
acetylenic alcohols are cleaved with KOH, the reaction
mixture contains water, which suggests another mecha-
nism. The authors of the paper14 actually led to the same
conclusion, showing that the cleavage of tertiary diace-
tylenic alcohols in the presence of proton donors pre-
vents isomerization of the resulting terminal diynes and
increases the reaction rate. We believe that both a proton
donor (e.g., water or alcohol) and tertiary acetylenic
alcoholate are involved in the elementary reaction event.
It is known that crown ethers can form 1 : 1 or
"sandwich" complexes with metal cations of different
sizes, which makes it difficult to predict a priori
the behavior of their ethynyl derivatives in reac-
tions in the presence of CuI salts (the Mannich,
Cadiot—Chodkiewicz, and Hay reactions) or inorganic
bases (the retro-Favorsky reaction, i.e., cleavage of ter-
tiary acetylenic alcohols).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 831—836, May, 2001.
1066-5285/01/5005-868 $25.00 © 2001 Plenum Publishing Corporation

Acetylene derivatives of benzocrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 5, May, 2001
869
Scheme 1
O
O
O
O
O
O
O
O
O
O
O
O
b or c
a
I
R
n
n
n
1, 2, 3
5a, 6a,b, 7a
8, 9, 10
MeO
MeO
MeO
MeO
MeO
b
d
MeO
I
11
12
13
OH
4a,b = HC≡CR
R = C(OH)Me2 (a); SiMe3 (b). n = 1 (1, 5a, 8); 2 (2, 6a,b, 9); 3 (3, 7a, 10)
Reagents and conditions: a. 4a,b, NEt3, PdCl2(PPh3)2, CuI; b. KOH, PhH; c. KOH, MeOH; d. 4a, NEt3, PdCl2(PPh3)2, CuI.
Based on this assumption,
one can explain why the retro-
Favorsky reaction is impossible
for compounds 6a and 7a,
which contain a polyether frag-
ment capable of forming com-
plexes with the potassium cat-
ion. Although the formation of
alcoholate is favored by com-
plexation here, its cleavage seem
tion.15 Aminomethylation of alk-1-ynes accelerates sig-
nificantly in the presence of copper salts.16 Further
study of the Mannich reaction gave rise to its several
versions. Propargylamines are most often synthesized by
aminomethylating alkynes with a mixture of paraform
with secondary amines in dioxane in the presence of
CuCl; with a mixture of paraform with secondary amines
in the presence of Cu(OAc)2 and sulfuric acid; or with
diaminomethanes in the presence of CuCl.12b For this
reason, the Mannich reaction is discussed below only
under these conditions.
The aminomethylation of ethynylbenzocrown ethers
9 and 10 with a mixture of paraform with acyclic
secondary amines 14c,d in dioxane in the presence of
12 mol % CuCl in an atmosphere of argon gave the
corresponding Mannich bases 17c,d and 18c,d. How-
ever, the reactions with cyclic amines 14a,b under
analogous conditions unexpectedly resulted, upon treat-
ing the reaction mixtures in the air, in disubstituted
butadiynes 19 and 20 in 80—86% yields rather than
aminomethylation products (Scheme 2).
The structures of diynes 19 and 20 were confirmed
by spectral data; in addition, they were synthesized
independently by oxidative dimerization of com-
pounds 9 and 10 according to the Hay method17
(see Scheme 2). Alkynes 9 and 10 are oxidized by
atmospheric oxygen in pyridine at 35—40 °C within
1—1.5 h. Under these conditions, dehydrodimerization
gives the corresponding butadiyne (19 or 20) as the sole
product.
Previously, various acetylene derivatives have been
aminomethylated, never yielding products of oxidative
dimerization.12 To reveal the factors influencing such a
reaction outcome, we carried out a series of experiments
and found the following:
R´
O
K
C
H
O
R
C
C
Me
Me
R´ = H, Alk
to be prevented within the framework of the discussed
process.
It follows from the above reasoning that compounds
containing substituents with analogous electron-donat-
ing properties but exhibiting no complexation effect can
be involved in the retro-Favorsky reaction in the pres-
ence of catalytic amounts of KOH. Indeed, derivatives
of veratrole 12 and benzo-12-crown-4 (5a) are cleaved
in boiling benzene in the presence of 5—10 mol %
KOH (see Scheme 1).
The starting alcohols 5a, 6a, 7a, and 12 were pre-
pared by cross-coupling of aryl iodides 1, 3, and 11 with
2-methylbut-3-yn-2-ol (4a) in 70—90% yields.
Ethynylbenzocrown ethers can also be obtained in a
different way. For example, the reaction of iodobenzo-
crown ether 2 with trimethylsilylacetylene 4b in the
presence of NEt3, PdCl2(PPh3)2, and CuI gives a
trimethylsilylethynyl derivative of benzocrown ether 6b.
When treated with 20% methanolic KOH at 25 °C,
compound 6b affords ethynylbenzocrown ether 9 (its
total yield is 84%) (see Scheme 1).
Aminomethylation of 4-ethynylbenzocrown ethers.
Aminomethylation of ethynylbenzocrown ethers is not
reported in the literature, though terminal acetylene
groups has long been involved in the Mannich reac-

870
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 5, May, 2001
Klyatskaya et al.
Scheme 2
SSQ-710 instrument (direct inlet, EI, 70 eV, ionization cham-
ber temperature 220—270 °C). Column chromatography was
carried out on KSK silica gel (60—200 µm). Preparative TLC
used a mixture of Al2O3 (high-purity grade) with a K-35
luminophore. The course of the reactions was monitored and
the purity of the reaction products was checked by TLC on
Silufol UV-254 plates. 2-Methylbut-3-yn-2-ol (4a) (Aldrich),
trimethylsilylacetylene (4b) (Fluka), PdCl2(PPh3)2 (Lancaster)
were not purified additionally before use. The known pro-
cedures were used to prepare 12-iodo-2,3,5,6,8,9-hexa-
hydro-1,4,7,10-tetraoxabenzocyclododecene (1),18 15-iodo-
2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-pentaoxabenzocyc-
lopentadecene (2), 18-iodo-2,3,5,6,8,9,11,12,14,15-deca-
hydro-1,4,7,10,13,16-hexaoxabenzocyclooctadecene (3),19
4-iodo-1,2-dimethoxybenzene (11),20 4-(morpholinome-
thyl)morpholine (15a),21 and 1-(piperidinomethyl)piperidine
(15b).22 The other reagents and solvents were prepared accord-
ing to the standard procedures.23
a
O
O
O
O
or b
or c
n
R
8, 9, 10
16a, 17a—d, 18a—c
O
O
O
O
d or e
n
2-Methyl-4-(2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-pen-
taoxabenzocyclopentadecen-15-yl)but-3-yn-2-ol (6a). A mix-
ture of iodide 2 (0.8 g, 2 mmol), alkyne 4a (0.24 mL, 3.3 mmol),
PdCl2(PPh3)2 (30 mg, 0.043 mmol), and CuI (15 mg,
0.15 mmol) in 2 mL of Et3N and 8 mL of PhH was stirred in
an atmosphere of argon at 70—75 °C for 1 h. When the
reaction was completed, the reaction mixture was cooled and
filtered through a SiO2 layer (2.5½2 cm). The solvent was
removed in vacuo, and the residue was recrystallized from
hexane. The yield of 6a was 0.6 g (86%), m.p. 64—66 °C.
1H NMR (CDCl3), δ: 1.45 (s, 6 H, CMe2); 2.02 (s, 1 H,
OH); 3.72—3.81 (m, 8 H, 4 OCH2); 3.87—3.95 (m, 4 H,
Ar(OCH2CH2)2); 4.10—4.17 (m, 4 H, Ar(OCH2)2); 6.41 (d,
1 H, H(6), J = 8.3 Hz); 6.98 (s, 1 H, H(3)); 7.12 (d, 1 H, H(5),
J = 8.3 Hz). IR, ν/cm–1: 2221 (C≡C); 3326 (br, OH).
Mass spectrum, m/z (Irel (%)): 350.1 [M]+ (21), 262.1
(11), 204.0 (15), 203.0 (100), 175.0 (13), 161.1 (12), 94.1
(10). Found: m/z 350.1734 [M]+. C19H26O6. Calculated:
M = 350.17292.
2
19, 20
MeO
MeO
f
13
O
N
21
14a—d = HR; 15a,b = CH2R2
R =
(a);
(b); NEt2 (c); NBu2 (d)
N
O
N
n = 1 (16a), 2 (17a—d), 3 (18a—c, 20)
Reagents and conditions: a. 14c,d, (CH2O)x, CuCl, dioxane;
b. 14a,b, Cu(OAc)2, 30% H2SO4, dioxane;
c. 15a,b, CuCl, dioxane; d. 14a,b, (CH2O)x, CuCl, dioxane;
e. 14a,b, O2, CuCl, Py; f. 14a, (CH2O)x, CuCl, dioxane.
2-Methyl-4-(2,3,5,6,8,9-hexahydro-1,4,7,10-tetraoxa-
benzocyclododecen-12-yl)but-3-yn-2-ol (5a) was obtained as
described for 6a, yield 91%, m.p. 63—65 °C (benzene—hex-
ane). 1H NMR (CD2Cl2), δ: 1.59 (s, 6 H, CMe2); 2.05 (s, 1 H,
OH); 3.67—3.75 (m, 4 H, 2 OCH2); 3.76—3.85 (m, 4 H,
Ar(OCH2CH2)2); 4.10—4.20 (m, 4 H, Ar(OCH2)2); 6.91 (d,
1 H, H(6), J = 7.5 Hz); 7.00—7.12 (m, 2 H, H(3), H(5)).
IR, ν/cm–1: 2145 (C≡C); 3216 (br, OH). Found (%): C, 66.72;
H, 7.19. C17H22O5. Calculated (%): C, 66.63; H, 7.23.
2-Methyl-4-(2,3,5,6,8,9,11,12,14,15-decahydro-
1,4,7,10,13,16-hexaoxabenzocyclooctadecen-18-yl)but-3-yn-2-
ol (7a) was obtained as described for 6a, yield 69%, m.p.
58—60 °C (hexane). 1H NMR (CDCl3), δ: 1.54 (s, 6 H,
CMe2); 2.04 (s, 1 H, OH); 3.69—3.82 (m, 12 H, 6 OCH2);
3.90—3.99 (m, 4 H, Ar(OCH2CH2)2); 4.12—4.20 (m, 4 H,
Ar(OCH2)2); 6.79 (d, 1 H, H(6), J = 8.2 Hz); 6.93 (s, 1 H,
H(3)); 7.01 (d, 1 H, H(5), J = 8.2 Hz). IR, ν/cm–1: 2200
(C≡C); 3357 (br, OH). MS, m/z (Irel (%)): 394.2 [M]+ (60),
217.9 (10), 202.8 (100), 186.9 (11), 174.9 (14), 160.8 (11), 145.1
(53), 93.8 (13), 88.9 (19), 72.9 (13). Found: m/z 394.1919 [M]+.
C21H30O7. Calculated: M = 394.19914.
1) the Mannich reactions with preliminarily pre-
pared bis-aminomethanes 15a,b give only the Mannich
bases 17a,b and 18a,b;
2) the Mannich reaction of 4-ethynylveratrole (13)
or crown ether 8 with morpholine 14a gives only the
Mannich bases 21 and 16a; and
3) the acid-catalyzed Mannich reactions of ethynyl-
benzocrown ethers 9 and 10 with amines 14a,b (in the
presence of H2SO4) give only the Mannich bases 17a,b
and 18a,b.
Thus, base-catalyzed homolytic linking of alkynes
rather than the Mannich reaction occurs in the presence
of CuCl only when cyclic amines 14a,b and ethynyl
derivatives of benzo-15-crown-5 (9) and benzo-18-
crown-6 (10) are used. These data suggest a specific
crown effect, but the mechanism of the formation of
dimeric products still remains unclear.
2-Methyl-4-(3,4-dimethoxyphenyl)but-3-yn-2-ol (12) was
obtained as described for 6a, yield 91%, m.p. 52—54 °C
(hexane). 1H NMR (CDCl3), δ: 1.66 (s, 6 H, CMe2);
2.02 (s, 1 H, OH); 3.89 (s, 6 H, 2 OMe); 6.79 (d, 1 H,
H(6), J = 7.7 Hz); 6.93 (s, 1 H, H(3)); 7.03 (d, 1 H,
H(5), J = 7.7 Hz). IR, ν/cm–1: 2235 (C≡C); 3574 (OH).
Found (%): C, 70.79; H, 7.62. C13H16O3. Calculated (%):
C, 70.89; H, 7.32.
Experimental
1H NMR spectra were recorded on a Bruker AM-300
spectrometer. IR spectra were recorded on a Bruker IFS-66
spectrometer (KBr). Mass spectra were recorded on a Finnigan

Acetylene derivatives of benzocrown ethers
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 5, May, 2001
871
Trimethyl-[2-(2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-
pentaoxabenzocyclopentadecen-15-yl)ethynyl]silane (6b). A
mixture of iodide 2 (1.8 g, 4.6 mmol), alkyne 4b (1.1 g,
11.5 mmol), PdCl2(PPh3)2 (80 mg, 0.11 mmol), and CuI
(40 mg, 0.4 mmol) in 3 mL of Et3N and 15 mL of PhH was
stirred in an atmosphere of argon at 40—45 °C for 2.5 h. When
the reaction was completed, the reaction mixture was cooled
and filtered through a SiO2 layer (2.5½2 cm). The solvent
was removed in vacuo, and the residue was recrystallized
from PhH—hexane. The yield of 6b was 1.5 g (87%),
m.p. 48—49.5 °C. 1H NMR (CDCl3), δ: 0.24 (s, 9 H,
SiMe3); 3.72—3.81 (m, 8 H, 4 OCH2); 3.87—3.95 (m, 4 H,
Ar(OCH2CH2)2); 4.10—4.17 (m, 4 H, Ar(OCH2)2); 6.77 (d,
1 H, H(6), J = 7.9 Hz); 6.97 (s, 1 H, H(3)); 7.06 (d, 1 H, H(5),
J = 7.9 Hz). IR, ν/cm–1: 2146 (C≡C). MS, m/z (Irel (%)):
364.2 [M]+ (34), 232.2 (17), 217.2 (100), 101.1 (16). Found:
m/z 364.169 [M]+. C19H28O5Si. Calculated: M = 364.17059.
15-Ethynyl-2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-penta-
oxabenzocyclopentadecene (9). A. A mixture of alkyne 6a
(1.4 g, 4 mmol) and calcined KOH (0.34 g, 6 mmol) in 30 mL
of PhH was refluxed for 2.5—3 h. Then the reaction mixture
was cooled and filtered through a SiO2 layer (2.5½2 cm), and
the solvent was removed in vacuo. The residue was recrystal-
lized from PhH—hexane. The yield of compound 9 was
0.73 g (63%).
B. A mixture of alkyne 6b (0.79 g, 2.2 mmol) and 20 mL of
10% methanolic KOH was stirred at ∼20 °C for 2—2.5 h. Then
the reaction mixture was filtered through a SiO2 layer
(2.5½2 cm). The solvent was removed, and the residue was
recrystallized from PhH—hexane. The yield of compound 9
was 0.62 g (97%), m.p. 60—61 °C. 1H NMR (CDCl3), δ: 2.75
(s, 1 H, C≡CH); 3.70—3.80 (m, 8 H, 4 OCH2); 3.85—3.95 (m,
4 H, Ar(OCH2CH2)2); 4.12—4.17 (m, 4 H, Ar(OCH2)2); 6.51
(d, 1 H, H(6), J = 8.3 Hz); 6.91 (s, 1 H, H(3)); 7.15 (d, 1 H,
H(5), J = 8.3 Hz). IR, ν/cm–1: 2221 (C≡C); 3281 (C≡CH).
MS, m/z (Irel (%)): 292.3 [M]+ (21), 204.1 (11), 161.1 (11),
160.1 (100.00), 145.1 (52), 134.1 (12), 131.1 (6), 105.1 (14),
104.1 (70), 89.1 (15). Found: m/z 292.13090 [M]+. C16H20O5.
Calculated: M = 292.13106.
(m, 4 H, Ar(OCH2)2); 6.91 (d, 1 H, H(6), J = 7.5 Hz); 7.11 (s,
1 H, H(3), J = 7.5 Hz); 7.15 (d, 1 H, H(5), J = 7.5 Hz). IR,
ν/cm–1: 2101 (C≡C); 3228 (C≡CH). Found (%): C, 67.53;
H, 6.39. C14H16O4. Calculated (%): C, 67.73; H, 6.50.
N,N-Diethyl-N-[3-(2,3,5,6,8,9,11,12-octahydro-
1,4,7,10,13-pentaoxabenzocyclopentadecen-15-yl)prop-2-
ynyl]amine (17c). A mixture of Et2NH (14c) (0.21 mL, 2 mmol),
paraform (0.06 g, 2 mmol), and 3 mL of dioxane was heated in
an atmosphere of argon at 45 °C for 30 min. CuCl (25 mg,
0.25 mmol) was added, and the reaction mixture was stirred
until a blue color appeared. Then compound 9 (0.52 g,
1.8 mmol) was added, and heating was continued at 80 °C for
2.5—3 h. When the reaction was completed, the reaction
mixture was filtered through an Al2O3 layer (2.5½2 cm), and
the solvent was removed in vacuo. The residue was recrystal-
lized from PhH—hexane to give compound 17c (0.49 g, 72%),
m.p. 51—52 °C. 1H NMR (CDCl3), δ: 1.15 (t, 6 H, Me,
J = 7.5 Hz); 2.60—2.71 (m, 4 H, N(CH2)2); 3.62 (s, 2 H,
CH2N); 3.74—3.81 (m, 8 H, 4 OCH2); 3.89—3.95 (m, 4 H,
Ar(OCH2CH2)2); 4.11—4.18 (m, 4 H, Ar(OCH2)2); 6.79 (d,
1 H, H(6), J = 7.5 Hz); 6.94 (s, 1 H, H(3)); 7.02 (d, 1 H, H(5),
J = 7.5 Hz). IR, ν/cm–1: 2220 (C≡C). MS, m/z (Irel (%)):
377.3 [M]+ (42), 376.3 (18), 363.4 (14), 362.3 (59), 305.3 (51),
217.2 (16), 174.2 (20), 173.2 (100), 147.1 (13), 115.1 (33),
107.6 (15.68). Found: m/z 377.22120 [M]+. C21H31NO5. Cal-
culated: M = 377.22021.
4-[3-(2,3,5,6,8,9-Hexahydro-1,4,7,10-tetraoxabenzo-
cyclododecen-12-yl)prop-2-ynyl]morpholine (16a) was obtained
from compound 8 and morpholine 14a by analogy with 17c
(oil, yield 65%). 1H NMR (CDCl3), δ: 2.59 (t, 4 H,
N(CH2CH2)2O, J = 4.4 Hz); 3.47 (s, 2 H, NCH2); 3.68—3.75
(m, 8 H, 2 OCH2, O(CH2CH2)2N); 3.77—3.83 (m, 4 H,
Ar(OCH2CH2)2); 4.11—4.18 (m, 4 H, Ar(OCH2)2); 6.9 (d,
1 H, H(6), J = 8.4 Hz); 7.01—7.08 (m, 2 H, H(3), H(6)). IR,
ν/cm–1: 2251 (C≡C). Amine 16a, picrate, yield 58%, m.p.
165—166.5 °C (from PhH). Found (%): C, 54.61; H, 5.03;
N, 9.11. C25H28N4O12•0.5PhH. Calculated (%): C, 54.63;
H, 5.08; N, 9.10.
N,N-Dibutyl-N-[3-(2,3,5,6,8,9,11,12-octahydro-
1,4,7,10,13-pentaoxabenzocyclopentadecen-15-yl)prop-2-
ynyl]amine (17d) was obtained from compound 9 and
dibutylamine 14d as described for 17c. Yield 62%, m.p.
98—100 °C (PhH—hexane). 1H NMR (CDCl3), δ: 0.94 (t,
6 H, 2 Me, J = 4.5 Hz); 1.28—1.35 (m, 4 H, 2 CH2Me);
1.53—1.64 (m, 4 H, 2 CH2CH2Me); 2.54—2.60 (m, 4 H,
N(CH2(CH2)2Me)2); 3.63 (s, 2 H, CH2N); 3.69—3.85 (m,
8 H, 4 OCH2); 3.86—3.99 (m, 4 H, Ar(OCH2CH2)2); 4.06—4.24
(m, 4 H, Ar(OCH2)2); 6.82 (d, 1 H, H(6), J = 8.2 Hz); 6.92 (s,
1 H, H(3)); 7.0 (d, 1 H, H(5), J = 8.2 Hz). IR, ν/cm–1: 2230
(C≡C). MS, m/z (Irel (%)): 433.1 [M]+ (32), 347.1 (20), 310.1
(22), 287.0 (21), 270.0 (20), 258.0 (42), 261.0 (100), 243.0
(20), 242.0 (83), 241.0 (36), 215.0 (29), 91.0 (41.61). Found:
m/z 433.5868 [M]+. C25H39NO5. Calculated: M = 433.5884.
N-[3-(2,3,5,6,8,9,11,12,14,15-Decahydro-1,4,7,10,13,16-
hexaoxabenzocyclooctadecen-18-yl)prop-2-ynyl]-N,N-diethyl-
amine (18c) was obtained from compound 10 by analogy with
17c (oil, yield 76%). 1H NMR (CDCl3), δ: 1.11 (t, 6 H, 2 Me,
J = 4.7 Hz); 2.62—2.68 (m, 4 H, N(CH2Me)2); 3.62 (s, 2 H,
CH2N); 3.67—3.86 (m, 12 H, 6 OCH2); 3.88—4.00 (m, 4 H,
Ar(OCH2CH2)2); 4.10—4.21 (m, 4 H, Ar(OCH2)2); 6.79 (d,
1 H, H(6), J = 8.8 Hz); 6.94 (s, 1 H, H(3)); 7.02 (d, 1 H, H(5),
J = 8.8 Hz). IR, ν/cm–1: 2220 (C≡C). Amine 18c, picrate,
yield 85%, m.p. 63—65 °C (from hexane). Found (%): C, 53.58;
H, 6.09; N, 8.80. C29H38N4O13. Calculated (%): C, 53.48;
H, 5.88; N, 8.60.
18-Ethynyl-2,3,5,6,8,9,11,12,14,15-decahydro-
1,4,7,10,13,16-hexaoxabenzocyclooctadecene (10) was obtained
as described for 9 from compound 7a in 69% yield, m.p.
95—96 °C (PhH—hexane). 1H NMR (CDCl3), δ: 3.00 (s, 1 H,
C≡CH); 3.75—3.82 (m, 12 H, 6 OCH2); 3.90—3.98 (m, 4 H,
Ar(OCH2CH2)2); 4.12—4.17 (m, 4 H, Ar(OCH2)2); 6.81 (d,
1 H, H(6), J = 8.1 Hz); 7.01 (s, 1 H, H(3)); 7.09 (d, 1 H, H(5),
J = 8.1 Hz). IR, ν/cm–1: 2225 (C≡C); 3229 (C≡CH). MS,
m/z (Irel (%)): 336.1 [M]+ (46), 176.1 (9), 175.1 (8), 190.1
(100), 161.1 (15), 145.0 (49), 134.1 (11), 105.1 (9), 104.0 (50),
89.0 (16). Found: m/z 336.15280 [M]+. C18H24O6. Calculated:
M = 336.15728.
4-Ethynyl-1,2-dimethoxybenzene (13) was obtained as de-
scribed for 9 from alcohol 12 (2.3 g, 10.5 mmol) in the
presence of KOH (0.06 g, 1.1 mmol). The yield of 13 was 1.5 g
(88%), m.p. 51—52 °C (hexane). 1H NMR (C6D6), δ: 2.82 (s,
1 H, C≡CH); 3.24 (s, 3 H, OMe(2)); 3.28 (s, 3 H, OMe(1));
6.37 (d, 1 H, H(6), J = 7.5 Hz); 6.98 (s, 1 H, H(3)); 7.15 (d,
1 H, H(5), J = 7.5 Hz). IR, ν/cm–1: 2230 (C≡C); 3244
(C≡CH). Found (%): C, 73.77; H, 6.03. C10H10O2. Calcu-
lated (%): C, 74.06; H, 6.21.
12-Ethynyl-2,3,5,6,8,9-hexahydro-1,4,7,10-tetraoxabenzo-
cyclododecene (8) was obtained as described for compound 13
from alcohol 5a in 50% yield, m.p. 57—59 °C (PhH—hexane).
1H NMR (CD2Cl2), δ: 3.07 (s, 1 H, C≡CH); 3.71—3.76 (m,
4 H, 2 OCH2); 3.76—3.85 (m, 4 H, Ar(OCH2CH2)2); 4.08—4.15

872
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 5, May, 2001
Klyatskaya et al.
4-[3-(3,4-Dimethoxyphenyl)prop-2-ynyl]morpholine (21)
was obtained from compound 13 and morpholine 14a by
analogy with 17c (oil, yield 60%). H NMR (CDCl3), δ: 2.77
1 H, H(6), J = 7.5 Hz); 6.94 (s, 1 H, H(3)); 6.78 (d, 1 H, H(5),
J = 7.5 Hz). IR, ν/cm–1: 2140 (C≡C). Amine 18a, picrate,
yield 71%, m.p. 79—81 °C (from PhH). Found (%): C, 56.81;
H, 5.89; N, 7.76. C29H36N4O14•PhH. Calculated (%): C, 56.60;
H, 5.66; N, 7.54.
1
(t, 4 H, N(CH2CH2)2O, J = 4.2 Hz); 3.56 (s, 2 H, CH2N);
3.78 (s, 6 H, 2 OMe); 3.84 (t, 4 H, N(CH2CH2)2O, J = 4.2 Hz);
6.91—7.03 (m, 3 H, arom.). IR, ν/cm–1: 2006 (C≡C). Amine
21, picrate, yield 69%, m.p. 111—113 °C (from PhH).
Found (%): C, 51.41; H, 4.62; N, 11.52. C21H22N4O10. Calcu-
lated (%): C, 51.43; H, 4.52; N, 11.42.
4-[3-(2,3,5,6,8,9,11,12-Octahydro-1,4,7,10,13-pentaoxa-
benzocyclopentadecen-15-yl)prop-2-ynyl]morpholine (17a).
A. A mixture of morpholine 14a (0.17 mL, 2 mmol) and
paraform (0.06 g, 2 mmol) in 3 mL of dioxane was heated in an
atmosphere of argon at 45 °C for 30 min. Cu(OAc)2 (25 mg,
0.17 mmol) and 1 mL of 30% H2SO4 were added, and the
reaction mixture was stirred until a blue color appeared. Then
compound 9 (0.52 g, 1.8 mmol) was added, and heating was
continued at 80 °C for 2.5—3 h. When the reaction was
completed, the reaction mixture was filtered through an Al2O3
layer (2.5½2 cm), and the solvent was removed in vacuo. The
residue was purified by preparative TLC on Al2O3 with
CHCl3—AcOEt (5 : 3) as the eluent to give compound 17a as
an oil (0.45 g, 87%).
1-[3-(2,3,5,6,8,9,11,12,14,15-Decahydro-1,4,7,10,13,16-
hexaoxabenzocyclooctadecen-18-yl)prop-2-ynyl]piperidine (18b)
was obtained in the form of an oil by analogy with 17a from
piperidine 14b and compound 10 in 67% yield (procedure A) or
from bis-amine 15b and compound 10 in 72% yield (proce-
dure B). 1H NMR (CDCl3), δ: 1.62—1.66 (m, 6 H, —(CH2)3—);
2.63 (t, 4 H, (CH2)2N, J = 3.3 Hz); 3.40 (s, 2 H, CH2N);
3.69—3.82 (m, 12 H, 6 OCH2); 3.90—3.98 (m, 4 H,
Ar(OCH2CH2)2); 4.12—4.16 (m, 4 H, Ar(OCH2)2); 6.72 (d,
1 H, H(6), J = 7.8 Hz); 6.89 (s, 1 H, H(3)); 7.05 (d, 1 H, H(5),
J = 7.8 Hz). IR, ν/cm–1: 2140 (C≡C). Amine 18b, picrate,
yield 71%, m.p. 96—98 °C (from AcOEt). Found (%): C, 54.44;
H, 5.53; N, 8.34. C30H38N4O13. Calculated (%): C, 54.38;
H, 5.78; N, 8.46.
1,4-Bis(2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-pentaoxa-
benzocyclopentadecen-15-yl)buta-1,3-diyne (19). A. Air was
bubbled through a mixture of compound 9 (0.58 g, 2 mmol)
and CuCl (50 mg, 0.5 mmol) in 20 mL of Py at 35—40 °C for
1—1.5 h. The reaction mixture was poured into 25 mL of water,
and the products were extracted with CHCl3 (3½15 mL). The
extract was washed with 20% HCl (3½20 mL) and water
(50 mL), dried over Na2SO4, and filtered through an Al2O3
layer (2.5½2 cm). The solvent was removed, and the residue
was crystallized from PhH—hexane to give compound 19 (0.35 g,
60%), m.p. 144—144.5 °C.
B. A mixture of amine 14a (0.1 g, 1.2 mmol) or compound
14b (0.1 g, 1.2 mmol) and paraform (0.04 g, 1.2 mmol) in 3 mL
of dioxane was heated in an atmosphere of argon at 45 °C for
30 min. CuCl (25 mg, 0.25 mmol) was added, and the reaction
mixture was stirred until a blue color appeared. Then com-
pound 9 (0.29 g, 1 mmol) was added, and heating was contin-
ued at 80 °C for 2.5—3 h. When the reaction was completed,
the reaction mixture was filtered through an Al2O3 layer
(2.5½2 cm), and the solvent was removed in vacuo. The residue
was crystallized from PhH—hexane to give compound 19 (0.21 g,
72.4%). 1H NMR (CDCl3), δ: 3.69—3.85 (m, 16 H, 8 OCH2);
3.88—4.04 (m, 8 H, 2 Ar(OCH2CH2)2); 4.16—4.28 (m, 8 H,
2 Ar(OCH2)2); 6.21 (d, 2 H, 2 H(6), J = 8.7 Hz); 6.83 (s, 2 H,
2 H(3)); 7.02 (d, 2 H, 2 H(5), J = 8.7 Hz). IR, ν/cm–1: 2141,
2200 (C≡C—C≡C). Found (%): C, 66.32; H, 6.75. C32H38O10.
Calculated (%): C, 65.96; H, 6.57.
1,4-Bis(2,3,5,6,8,9,11,12,14,15-decahydro-1,4,7,10,13,16-
hexaoxabenzocyclooctadecen-18-yl)buta-1,3-diyne (20) was
obtained as described for 19 according to procedures A in 68%
yield or B in 86% yield, m.p. 120—122 °C (PhH—hexane). 1H
NMR (CDCl3), δ: 3.69—3.86 (m, 24 H, 12 OCH2); 3.88—4.06
(m, 8 H, 2 Ar(OCH2CH2)2); 4.18—4.25 (m, 8 H, 2 Ar(OCH2)2);
6.81 (d, 2 H, H(6), J = 8.9 Hz); 7.02 (s, 2 H, H(3)); 7.12 (d,
2 H, H(5), J = 8.9 Hz). IR, ν/cm–1: 2140, 2210 (C≡C—C≡C).
Found (%): C, 64.85; H, 7.19. C36H46O12. Calculated (%):
C, 64.85; H, 6.96.
B. A mixture of bis-amine 15a (0.32 g, 1.7 mmol), com-
pound 9 (1 g, 3.4 mmol), CuCl (50 mg, 0.5 mmol), and 3 mL
of dioxane was heated in a flow of argon at 80 °C for 2—2.5 h.
The product was isolated in the form of an oil as described in
procedure A. The yield of 17a was 0.94 g (71%). 1H NMR
(CDCl3), δ: 2.59 (t, 4 H, N(CH2CH2)2O, J = 4.8 Hz); 3.46 (s,
2 H, CH2N); 3.65—3.75 (m, 12 H, 4 OCH2, O(CH2CH2)2N);
3.83—3.90 (m, 4 H, Ar(OCH2CH2)2); 4.06—4.12 (m, 4 H,
Ar(OCH2)2); 6.77 (d, 1 H, H(6), J = 8.2 Hz); 6.94 (s, 1 H,
H(3)); 7.02 (d, 1 H, H(5), J = 8.2 Hz). IR, ν/cm–1: 2141 (C≡C).
Picrate (general procedure). A hot solution of picric acid
(0.25 g, 1.1 mmol) in 5 mL of 95% EtOH was added to a hot
solution of amine 17a (0.5 g, 1.3 mmol) in 3 mL of 95% EtOH.
The precipitate that formed was filtered off and recrystallized
from PhH. Amine 17a, picrate, yield 0.69 g (86%), m.p.
1
171—172 °C. H NMR (DMSO-d6), δ: 3.71—3.78 (m, 4 H,
Ar(OCH2CH2)2); 4.06—4.14 (m, 4 H, Ar(OCH2)2); 6.99 (d,
1 H, H(6), J = 8.3 Hz); 7.06 (s, 1 H, H(3)); 7.11 (d, 1 H, H(5),
J = 8.2 Hz); 8.62 (s, 2 H, Ar), the other signals overlap the
solvent signals. IR, ν/cm–1: 1334, 1516 (NO2); 2246 (C≡C),
3611 (NH). Found (%): C, 56.70; H, 5.78; N, 8.15.
C27H32N4O13•PhH. Calculated (%): C, 56.73; H, 5.48; N, 8.01.
1-[3-(2,3,5,6,8,9,11,12-Octahydro-1,4,7,10,13-pentaoxa-
benzocyclopentadecen-15-yl)prop-2-ynyl]piperidine (17b) was
obtained as described for 17a from piperidine 14b and com-
pound 9 (procedure A) in 64% yield or from bis-amine 15b and
compound 9 (procedure B) in 60% yield, m.p. 70—72 °C
1
(PhH—hexane). H NMR (CD2Cl2), δ: 1.59—1.63 (m, 6 H,
(CH2)3); 2.53 (t, 4 H, (CH2)2N, J = 3.1 Hz); 3.41 (s, 2 H,
CH2N); 3.69—3.80 (m, 8 H, 4 OCH2); 3.85—3.93 (m, 4 H,
Ar(OCH2CH2)2); 4.01—4.09 (m, 4 H, Ar(OCH2)2); 6.79 (d,
1 H, H(6), J = 8.3 Hz); 6.93 (s, 1 H, H(3)); 7.00 (d, 1 H, H(5),
J = 8.3 Hz). IR, ν/cm–1: 2200 (C≡C). Found (%): C, 67.92;
H, 8.15; N, 3.45. C22H31NO5. Calculated (%): C, 67.84;
H, 8.02; N, 3.59.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 99-03-
32877).
4-[3-(2,3,5,6,8,9,11,12,14,15-Decahydro-1,4,7,10,13,16-
hexaoxabenzocyclooctadecen-18-yl)prop-2-ynyl]morpholine
(18a) was obtained in the form of an oil by analogy with 17a
from compound 10 in 75% (procedure A) and 76% yield
(procedure B). 1H NMR (CDCl3), δ: 2.68—2.59 (m, 4 H,
N(CH2CH2)2O); 3.48 (s, 2 H, CH2N); 3.65—3.83 (m,
16 H, 6 OCH2, O(CH2CH2)2N); 3.88—3.98 (m, 4 H,
Ar(OCH2CH2)2); 4.11—4.20 (m, 4 H, Ar(OCH2)2); 6.79 (d,
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Received January 24, 2000;
in revised form October 31, 2000