Synthesis of monoazacrown ethers under phase-transfer catalysis

Article abstract of DOI:10.1134/S1070428012100156

A procedure has been proposed for the synthesis of monoazacrown ethers by reaction of N-benzyldiethanolamine with oligo(ethylene glycol) bis-p-toluenesulfonates in a two-phase system aromatic hydrocarbon-50% aqueous alkali, followed by removal of the benzyl group by catalytic hydrogenolysis. The maximal yields of N-benzylaza-12-crown-4, -18-crown-6, and -21-crown-7 were achieved by adding 4-10 equiv of LiCl, BaBr₂, and CsCl, respectively, to the reaction mixture, which probably indicated template effect. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012100156

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 10, pp. 1345–1352. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © N.G. Luk’yanenko, S.S. Basok, E.Yu. Kulygina, T.Yu. Bogashchenko, I.S. Yakovenko, 2012, published in Zhurnal Organicheskoi
Khimii, 2012, Vol. 48, No. 10, pp. 1350–1357.
Synthesis of Monoazacrown Ethers
under Phase-Transfer Catalysis
†
N. G. Luk’yanenko , S. S. Basok, E. Yu. Kulygina, T. Yu. Bogashchenko, and I. S. Yakovenko
Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine,
Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine
e-mail: Kulgina54@gmail.com
Received February 13, 2012
Abstract—A procedure has been proposed for the synthesis of monoazacrown ethers by reaction of N-ben-
zyldiethanolamine with oligo(ethylene glycol) bis-p-toluenesulfonates in a two-phase system aromatic hydro-
carbon–50% aqueous alkali, followed by removal of the benzyl group by catalytic hydrogenolysis. The
maximal yields of N-benzylaza-12-crown-4, -18-crown-6, and -21-crown-7 were achieved by adding 4–
1
0 equiv of LiCl, BaBr
2
, and CsCl, respectively, to the reaction mixture, which probably indicated template
effect.
DOI: 10.1134/S1070428012100156
Persistent interest in azacrown ethers over past
decades [1] is related primarily to their unusual com-
plexing properties which may be regarded as inter-
mediate between the properties of crown ethers that
firmly bind alkali and alkaline-earth metal cations and
cyclic polyamines that form stable complexes with
heavy and transition metal ions. In addition, azacrown
ethers attract attention as convenient starting com-
pounds for the synthesis of various lariat crown ethers,
including those containing chromogenic, fluorescent,
photochromic, and other fragments, bis-crown ethers,
and biologically active substances based thereon.
reported. 1-Benzyl-1-aza-12-crown-4 is generally syn-
thesized from benzylamine and diiodide derived from
tetraethylene glycol [11].
The above listed procedures require large volumes
of anhydrous solvents and large amounts of alkali
metal hydrides or tert-butoxides as bases and ensure
relatively low yields of monoazacrown ethers, which
strongly restricts the scope of their practical applica-
tion. In some cases, additional purification of the target
products by column chromatography [3] or by trans-
formation into complexes with alkali metal thiocy-
anates [2] is necessary.
Monoazacrown ethers are generally prepared by
alkylation of unsubstituted or N-protected diethanol-
amine with the corresponding oligo(ethylene glycol)
bis-p-toluenesulfonates or dichlorides in the presence
of alkali metal tert-butoxides or sodium hydride in
anhydrous solvents (t-BuOH, dioxane, THF, DMSO,
or DMFA) and subsequent removal of the protecting
group [2–4]. Intramolecular cyclization of N,N-bis-
We previously showed [12] that di- and polyaza-
crown ethers and cryptands can be synthesized under
conditions of phase-transfer catalysis. Taking into
account that the described procedure is free from the
above disadvantages, in the present work we devel-
oped a convenient method for the synthesis of mono-
azacrown ethers via macrocyclization of N-benzyldi-
ethanolamine with oligo(ethylene glycol) bis-p-tolu-
enesulfonates in a two-phase system, followed by
removal of the benzyl group from intermediate
N-benzylmonoazacrown ethers.
(
oligooxyethylene)amines in the presence of an equi-
molar amount of arenesulfonyl chloride or excess
alkali metal hydroxide in dioxane [5] and reaction of
p-toluenesulfonamide with oligo(ethylene glycol) bis-
p-toluenesulfonates [6] were used more rarely. As
protecting groups, p-toluenesulfonyl [7], triphenyl-
methyl [8], benzyl [9], and cyano groups [10] were
Initial oligo(ethylene glycol) bis-p-toluenesul-
fonates Ia–Ie were synthesized by acylation of the
corresponding glycols with p-toluenesulfonyl chloride
in a two-phase system consisting of an organic solvent
and aqueous sodium hydroxide in the presence of
†
Deceased.
1
345

1
346
LUK’YANENKO et al.
Scheme 1.
TsCl, organic solvent–aq. NaOH
R NX or BTEAC
4
HO
OH
TsO
OTs
X
X
Ia–Ie
2 2 2 2 2 2 2 3 6 4
X = O (a), OCH CH O (b), O(CH CH O) (c), O(CH CH O) (d), o-OC H O (e).
Table 1. Reaction of oligo(ethylene glycols) with p-toluenesulfonyl chloride
Compound
no.
Concentration
of NaOH, %
Base
Et
Organic solvent Temperature, °C
Catalyst
Yield, %
Ia
3
N
–
15
Dioxane
5
–
80
46
61
84
86
78
76
77
69
65
65
83
82
68
85
74
76
86
86
67
90
96
84
94
80
87
85
52
82
90
90
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
CH
CH
CH
CH
CH
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
5
BTEAC
BTEAC
BTEAC
BTEAC
BTEAC
BTEAC
BTEAC
20
5
30
5
35
5
45
5
30
THF
THF
5
20
5
30
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
5
Bu
Bu
–
4
4
NBr
NI
30
5
30
5
30
5–10
BTEAC
BTEAC
–
30
8–20
30
8–20
Ib
Et
3
N
–
Dioxane
Dioxane
Dioxane
5
–
NaOH
NaOH
NaOH
NaOH
NaOH
0.17.5
0.17.5
30
5
BTEAC
–
8–21
CH
CH
CH
2
2
2
Cl
2
Cl
2
Cl
2
5
BTEAC
BTEAC
30
8–20
30
10–150
Bu
–
4
NBr
Ic
Id
Ie
Et
NaOH
Et
NaOH
Et
3
N
–
Dioxane
CH Cl
Dioxane
CH Cl
5
30
2
2
5–15
BTEAC
–
3
N
–
5
30
2
2
5–15
BTEAC
–
3
N
–
Dioxane
THF
5
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
0.17.5
0.17.5
30
5
–
Dioxane
Chloroform
5
5
–
BTEAC
BTEAC
BTEAC
BTEAC
30
CH
CH
CH
2
2
2
Cl
2
Cl
2
Cl
2
5
30
10–150
16–200
30
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF MONOAZACROWN ETHERS UNDER PHASE-TRANSFER CATALYSIS
1347
Table 2. Yields of N-benzylazacrown ethers IIa–IIe, depending on the nature and amount of phase-transfer catalyst and
a
temperature
Comp.
no.
Amount of
catalyst, mol
Tempera-
ture, °C
Comp.
no.
Amount of Tempera-
catalyst, mol ture, °C
Catalyst
Yield, %
Catalyst
Yield, %
IIa
IIb
IIc
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
4
4
4
4
4
4
4
4
4
NBr
NI
0.25
0.25
0.25
0.25
0.25
0.25
0.15
0.10
0.30
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.15
0.10
0.30
00.025
0.25
0.25
0.25
55
60
65
70
75
85
65
65
65
70
70
55
60
65
70
75
85
70
70
70
70
70
55
60
39
63
70
71
65
48
64
38
70
47
56
30
63
78
75
66
50
67
47
74
43
22
33
60
IIc
Bu
Bu
Bu
Bu
Bu
Bu
Bu
4
4
4
4
4
4
4
NI
0.25
0.25
0.25
0.25
0.15
0.10
0.25
0.25
0.25
0.25
0.25
0.25
0.10
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.10
0.25
0.25
65
70
75
85
70
70
70
70
55
65
70
85
70
65
65
55
60
65
70
75
85
65
65
65
69
73
58
46
65
41
48
17
26
56
58
32
27
27
21
31
67
42
70
63
40
38
33
12
NBr
NBr
NBr
NBr
NBr
NCl
NI
NBr
NI
NBr
NI
NI
4
Et NBr
NI
IId
Bu
Bu
Bu
Bu
Bu
4
4
4
4
4
NI
BTEAC
NI
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
4
4
4
4
4
4
4
4
4
4
4
NCl
NBr
NBr
NI
NBr
NI
NBr
BTEAC
Et NBr
NBr
NBr
NBr
NBr
NBr
NBr
NHSO
4
IIe
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
4
4
4
4
4
4
4
4
NBr
NBr
NBr
NBr
NBr
NBr
NBr
NCl
4
4
Et NBr
Bu
Bu
4
4
NBr
NBr
4
Et NI
a
Molar ratio N-benzyldiethanolamine–I 1:1.
quaternary ammonium salts (Scheme 1). Unlike known
methods [13–15], this procedure requires neither low
temperature conditions nor additional purification of
oily tetra- and pentaethylene glycol bis-p-toluenesul-
fonates by column chromatography.
alyst was benzyltriethylammonium chloride (BTEAC)
(as compared to Bu NBr and Bu NI). The yield of
Ia–Ie almost did not depend on the temperature in the
4
4
range from 0 to 20°C.
Bis-p-toluenesulfonates Ia–Ie were brought into
reaction with N-benzyldiethanolamine in a two-phase
system aromatic hydrocarbon–50% aqueous alkali in
the presence of a quaternary ammonium salt. As
aromatic solvent we used benzene, toluene, or xylene
(Scheme 2). Decrease of the alkali concentration below
The data in Table 1 show that, among the examined
solvents, methylene chloride and THF ensured the best
results, regardless of the concentration of alkali and
catalyst nature. The optimal concentration of alkali
was 30–35%, and the most efficient phase-transfer cat-
Scheme 2.
O
ArH–50% NaOH
R NX or BTEAC
HO
OH
4
TsO
OTs
N
X
+
PhCH
2
N
X
CH Ph
2
O
Ia–Ie
IIa–IIe
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

1
348
LUK’YANENKO et al.
Table 3. Effect of the ratio of the aqueous and organic
phases on the yield of N-benzylazacrown ethers IIa–IIe
the reaction catalyzed by tetrabutylammonium bro-
mide and 65±2°C in the reaction with Bu NI. Lower
4
yields of N-benzylazacrown ethers at lower or higher
temperature (Table 2) may be rationalized by reduction
of the rate of macrocyclization or formation of
a considerable amount of oligomeric products due to
increased rate of polycondensation.
Compound
no.
Volume ratio 50% NaOH–
benzene, ml
Yield, %
a
IIa
50:650 (1:13)
33
41
61
71
72
71
34
65
75
71
55
68
73
29
49
58
32
63
70
6
8
1
3
4
5:635 (1:9.8)
7.5:612.5 (1:7)
00:600 (1:6)
50:350 (1:1)
00:300 (1:0.75)
The reactant concentration also appreciably affect-
ed the yield of the cyclization products. The maximal
yields were obtained at a concentration of 0.01–
0.11 M. Increase in their concentration was accom-
panied by reduction of the yield and strong tarring,
whereas insignificant increase of the yield at lower
concentration (<0.01 M) cannot be regarded as profit-
able because of considerable reduction of the yield per
unit volume of the reaction mixture.
IIb
50:650 (1:13)
8
1
4
7.5:612.5 (1:7)
00:600 (1:6)
00:300 (1:0.75)
b
IIc
65:635 (1:9.8)
In addition, an important factor was the volume
ratio of the aqueous and organic phases, the optimal
value being 1:6. Raising the fraction of the organic
solvent resulted in reduced yield, whereas increase in
the fraction of aqueous alkali did not affect the yield,
but led to inefficient consumption of NaOH (Table 3).
One more important factor determining the yield of
N-benzylazacrown ethers was the nature of alkali. The
maximal yield of 15-membered azacrown ethers was
obtained with the use of NaOH, while KOH and CsOH
were the most efficient in the synthesis of 1-benzyl-1-
aza-18-crown-6 (IIc) and 1-benzyl-1-aza-21-crown-7
8
1
2.5:612.5 (1:7)
00:600 (1:6)
c
IId
50:650 (1:13)
8
1
2.5:612.5 (1:7)
00:600 (1:6)
IIe
65:635 (1:9.8)
8
1
2.5:612.5 (1:7)
00:600 (1:6)
a
b
c
In the presence of LiCl,
In the presence of KBr,
In the presence of CsCl.
(IId), respectively. Taking into account that a 50% so-
5
0% led to sharp reduction of the yield of target
lution of LiOH cannot be prepared and that the reac-
tion at lower concentration of alkali gives unsatisfac-
tory results, 1-benzyl-1-aza-12-crown-4 (IIa) was syn-
thesized in 45% yield using a 50% solution of NaOH
containing 5–10 equiv of LiOH (with respect to Ia).
azacrown ethers IIa–IIe, presumably as a result of
increase of the rate of hydrolysis of both initial bis-p-
toluenesulfonates and diethanolamine salt. The yield of
IIa–IIe strongly depended on the nature and amount of
phase-transfer catalyst and on the temperature. The
optimal ratio catalyst–N-benzyldiethanolamine–I was
These findings indicated template effect of metal
cation, which is well known in the synthesis of macro-
cyclic polyethers but still remains questionable as
applied to azacrown ethers [9, 16]. Some authors [17]
presumed dual template effect of metal cation in the
synthesis of azacrown ethers. We examined the effect
of addition of alkali and alkaline-earth metal salts on
the yield of N-benzylazacrown ethers. The reactions
were carried out under the same conditions as above,
but 2–10 equiv of the corresponding metal salt was
added to the aqueous phase (Table 4). The yield of IIa
considerably increased in the presence of lithium salts
and attained its maximal value upon addition of 4–
10 equiv of LiHlg. In the synthesis of 1-benzyl-1-aza-
15-crown-5 (IIb), addition of metal salts did not
produce an appreciable effect on the yield if aqueous
0
.25:1:1 (Table 2); this ratio ensured the best yields of
the cyclic products. Reduction of the amount of the
catalyst resulted in a lower yield of azacrown ethers,
whereas increase of the catalyst concentration did not
affect the yield of II to an appreciable extent, but
hampered isolation of the products, so that the use of
a larger amount of the catalyst is undesirable. Change
of the reactant ratio to non-equimolar also strongly
reduced the yield and favored formation of a large
amount of polymeric products.
Among the examined catalysts (Bu NI, Bu NBr,
4
4
Bu NCl, Et BnNCl, Bu NHSO , Et NI, and Et NBr),
tetrabutylammonium bromide and iodide showed the
best results. The optimal temperature was 70±2°C in
4
3
4
4
4
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF MONOAZACROWN ETHERS UNDER PHASE-TRANSFER CATALYSIS
1349
Table 4. Effect of the nature and amount of added salt on the yield of N-benzylazacrown ethers IIa–IIe
Compound
no.
Amount
of salt, mol
Compound
no.
Amount
of salt, mol
Base
Salt
Yield, %
Base
Salt
Yield, %
IIa
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
–
00
02
01
02
04
08
10
04
10
04
04
00
04
04
0.02.7
00
04
00
04
00
2
42
25
54
56
71
71
72
71
72
48
58
72
70
68
58
61
72
44
69
51
45
69
56
63
73
IIc
NaOH
NaOH
NaOH
NaOH
KOH
CsCl
RbCl
04
04
04
04
00
04
00
02
00.3.3
00.4.7
10
10
00
04
04
04
00
00
04
06
4
71
48
65
74
59
72
36
36
37
49
58
47
42
41
46
50
48
70
65
63
67
58
66
39
68
LiClO
LiCl
LiCl
LiCl
LiCl
LiCl
LiBr
LiBr
NaBr
LiCl
–
4
SrCl
2
BaBr
–
2
KOH
BaBr
–
2
IId
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
KOH
CsClO
CsCl
CsCl
CsCl
4
IIb
IIc
NaOH
NaOH
NaOH
NaOH
KOH
BaBr
–
2
LiCl
NaBr
KOH
CsClO
RbCl
4
BaBr
–
2
KOH
IId
IIe
KOH
BaBr
2
KOH
NaBr
–
CsOH
NaOH
NaOH
NaOH
NaOH
KOH
–
CsOH
CsOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
–
NaBr
–
LiBr
NaCl
KClO
KCl
KBr
KBr
KBr
4
SrCl
2
6
–
0
5
KOH
NaBr
–
4
7
CsOH
CsOH
0
10
NaCl
4
a
Molar ratio N-benzyldiethanolamine–I 1:1.
sodium hydroxide was used. However, the yield of
IIb increased upon addition of sodium salts when the
reaction was carried out using aqueous KOH or CsOH.
Higher yield of 1-benzyl-1-aza-18-crown-6 (IIc) was
favored by the presence of potassium, cesium, or
barium salts, and addition of 10 equiv of CsCl ensured
the best yield of 1-benzyl-1-aza-21-crown-7 (IId).
These findings allowed us to presume template effect
in the synthesis of N-benzylazacrown ethers under
phase-transfer catalysis.
change reaction (2) with quaternary ammonium salt,
–
+
and lipophilic ion pair RO Q thus formed is trans-
ferred to the organic phase where the alkoxide ion
undergoes alkylation with the corresponding bis-p-
toluenesulfonate [reaction (3)]. Deprotonation of inter-
mediate A yields anion B [reaction (4)] which is con-
verted into cation-associated structure C as precursor
of azacrown ether. The process is completed by intra-
molecular cyclization (5). Obviously, the formation of
associate C is the key step determining the yield of
cyclization products. By analogy with crown ethers
[19], we believe that the stability of intermediate C is
directly related to the stability of the complex formed
by the cyclization product with one or another metal
cation. Presumably, in the presence of metal salts the
metal ion in intermediate C is replaced by a metal ion
On the basis of general relations holding in nucleo-
philic reactions occurring in two-phase systems [18],
the formation of N-benzylazacrown ethers may be
illustrated by Scheme 3. Obviously, the first step is
generation of alkoxide ion in the aqueous phase or at
the phase boundary [reaction (1)]. Next follows ex-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

1
350
LUK’YANENKO et al.
Scheme 3.
–
+
HO
HO
OH
HO
O M
N
N
(
1)
+
MOH
+
H O
2
CH Ph
CH Ph
2
2
–
+
O Q+
–
O M
HO
N
N
+
QY
+
MY
(2)
CH Ph
CH Ph
2
2
HO
O Q+
–
HO
O
OTs
N
N
X
+
TsO
OTs
+
QOTs (3)
X
CH Ph
CH Ph
2
2
HO
O
OTs
M+ –O
O
OTs
N
X
N
X
+
MOH
+
H O (4)
2
CH Ph
CH Ph
2
2
A
B
O
M
O
O
M
X
X
TsO–
PhCH2
N
PhCH2
N
(5)
O
OTs
C
which fits better the macroring cavity (Scheme 4). As
a result, the yield of N-benzylazacrown ethers depends
on the nature of metal cations present in the reaction
mixture.
tion time 7–8 h). Addition of a catalytic amount of
acetic or concentrated hydrochloric acid made it
possible to shorten the reaction time to 3–5 h. Addition
of a larger amount of acid almost did not accelerate the
process but hindered isolation of the products.
Scheme 4.
O
M1
O
O
M2
O
EXPERIMENTAL
2
M X
X
X
PhCH2
N
PhCH2
N
1
The H NMR spectra were recorded on a Varian
VXR-300 spectrometer operating at 300 MHz. The
mass spectra (electron impact, 70 eV) were obtained
on an MKh-1321 instrument with direct sample admis-
sion into the ion source heated to 200°C. The purity of
the isolated compounds was checked by TLC (Silufol
UV-254) and GLC (Chrom-5 chromatograph equipped
with a flame-ionization detector; stationary phase 5–
10% of SE-30, OV-17, or SP-2100 on Chromaton
N-AW-HMDS or Inerton; carrier has helium; the
carrier gas flow rate and oven temperature depended
on the properties of compounds being analyzed).
OTs
OTs
Thus the optimal conditions for the synthesis of
N-benzylazacrown ethers in a two-phase system are as
follows: (1) volume ratio benzene–50% aqueous
NaOH 1:6, (2) reactant concentration 0.01–0.11 M,
3) tetrabutylammonium iodide or bromide (25 mol %)
as catalyst, and (4) temperature 65–70°C. In the syn-
theses of 1-benzyl-1-aza-12-crown-4, 1-benzyl-1-aza-
8-crown-6, and 1-benzyl-1-aza-21-crown-7, 4 to
0 equiv of LiCl, BaBr , or CsCl, respectively, should
be added to the aqueous phase.
(
1
1
2
Oligo(ethylene glycol) bis-p-toluenesulfonates
Ia–Ie (general procedure). A solution of 63 g
(0.33 mol) of p-toluenesulfonyl chloride in 75 ml of
methylene chloride was added over a period of 0.5 h
under vigorous stirring to a mixture of 0.15 mol of the
corresponding oligo(ethylene glycol), 150 ml of meth-
ylene chloride, 1.35 g (6 mmol) of benzyltriethylam-
monium chloride, and 115 ml of 30% aqueous sodium
hydroxide. The mixture was stirred for 6 h, the organic
phase was separated, washed with water (3×75 ml),
Deprotection of N-benzylazacrown ethers is gener-
ally performed by catalytic hydrogenation over palla-
dium catalyst (10% Pd/C) in anhydrous ethanol or
acetic acid under a hydrogen pressure of 3–5 atm
(
reaction time 15–25 h) [1, 12, 13]. We found that
benzyl group can be removed from compounds IIa–
IId by the action of hydrogen over 10% Pd/C under
atmospheric pressure in reagent-grade methanol (reac-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SYNTHESIS OF MONOAZACROWN ETHERS UNDER PHASE-TRANSFER CATALYSIS
1351
1
dried over anhydrous sodium sulfate, and evaporated
under reduced pressure, and the residue was recrys-
tallized from ethanol or methanol (oily products were
used without additional purification).
(0.05 mm). H NMR spectrum (CDCl ), δ, ppm: 2.63 t
3
(4H, CH N), 3.50 m (26H, CH O, CH Ph), 7.08 s (5H,
C H ). Mass spectrum: m/z 397 [M] .
2
2
2
+
6
5
8
,9-Benzo-1-benzyl-1-aza-15-crown-5 (IIe). Reac-
Diethylene glycol bis-p-toluenesulfonate (Ia).
Yield 83%, mp 89°C; published data [14, 15]:
mp 88–89°C.
tion time 7 h. Yield 70%, oily substance (the product
was not subjected to additional purification). H NMR
1
spectrum (CDCl ), δ, ppm: 2.63 t (4H, CH N), 3.52 s
3
2
(
C
2H, CH Ph), 3.56 m (8H, CH O), 3.62 m (4H,
Triethylene glycol bis-p-toluenesulfonate (Ib).
Yield 86%, mp 80–81°C [14, 15].
2
2
H
OCH
), 6.78 m (4H, C
H
), 7.00 s (5H, C H ).
6
4
2
6
4
6 5
+
Mass spectrum: m/z 357 [M] .
Tatraethylene glycol bis-p-toluenesulfonate (Ic).
Yield 96%, oily substance.
Removal of benzyl protection (general proce-
dure). A mixture of 2 g of 10% Pd/C and 50 ml of
methanol was saturated with hydrogen over a period of
Pentaethylene glycol bis-p-toluenesulfonate (Id).
Yield 94%, oily substance.
1
0
h under stirring on a magnetic stirrer, a solution of
.1 mol of azacrown ether IIa–IIe and 1 ml of acetic
Benzene-1,2-diylbis(oxyethane-2,1-diyl) bis-p-
toluenesulfonate (Ie). Yield 90%, mp 98–100°C;
published data [9]: mp 95–96°C.
acid in 200 ml of methanol was added, and the mixture
was stirred for 4–5 h in a stream of hydrogen. The
catalyst was filtered off and washed with methanol
N-Benzylazacrown ethers IIa–IIe (general proce-
dure). A solution of 0.05 mol of compound Ia–Ie in
(
3×20 ml), the filtrate was combined with the wash-
6
00 ml of benzene was added to a mixture of 9.75 g
ings and evaporated to dryness under reduced pressure,
the residue was dissolved in 60–70 ml of water, and
the solution was extracted with benzene (3×50 ml).
The benzene extracts were discarded, the aqueous
phase was made alkaline by adding NaOH to pH 9–10
and extracted with methylene chloride or chloroform
(0.05 mol) of N-benzyldiethanolamine, 4.025 g
(
0.0125 mol) of tetrabutylammonium bromide, and
1
00 ml of 50% aqueous NaOH, and the mixture was
stirred for 7–25 h at 70±2°C. The mixture was cooled,
the organic phase was separated, washed with water
(
3×100 ml), and evaporated under reduced pressure,
the residue was treated with boiling hexane (3×
50 ml), the extract was evaporated under reduced
pressure, and the residue was distilled in a vacuum.
-Benzyl-1-aza-12-crown-4 (IIa). Lithium chlo-
(
7×50 ml). The solvent was distilled off, the residue
was treated with boiling hexane (3 × 100 ml), the
extract was evaporated to dryness under reduced
pressure, and the residue was distilled under reduced
pressure.
1
1
ride, 8.5 g (0.2 mol), was added to the aqueous phase;
1
-Aza-12-crown-4. bp 85–91°C (0.05 mm);
reaction time 25 h. Yield 71%, bp 140–142°C
1
mp 59–60°C [11]. H NMR spectrum (CDCl ), δ, ppm:
.48 m (1H, NH), 2.62 t (4H, CH N), 3.59 t (12H,
1
3
(
(
0.05 mm). H NMR spectrum (CDCl ), δ, ppm: 2.60 t
3
2
2
+
4H, CH N), 3.42 m (14H, CH O, CH Ph), 7.07 s (5H,
C H ). Mass spectrum: m/z 265 [M] .
2
2
2
CH O). Mass spectrum: m/z 175 [M] .
+
2
6
5
1
-Aza-15-crown-5. bp 98–100°C (0.05 mm),
1
-Benzyl-1-aza-15-crown-5 (IIb). Reaction time
1
1
mp 30–32°C [10]. H NMR spectrum (CDCl
.50 m (1H, NH), 2.75 t (4H, CH N), 3.55 m (16H,
3
), δ, ppm:
1
0 h. Yield 72%, bp 148–153°C (0.05 mm). H NMR
2
2
+
spectrum (CDCl ), δ, ppm: 2.62 t (4H, CH N), 3.45 m
3
2
CH O). Mass spectrum: m/z 219 [M] .
2
(
18H, CH O, CH Ph), 7.08 s (5H, C H ). Mass spec-
2 2 6 5
+
trum: m/z 309 [M] .
1-Aza-18-crown-6. bp 110–112°C (0.05 mm),
mp 49–51°C [19]. H NMR spectrum (CDCl ), δ, ppm:
.52 m (1H, NH), 2.81 t (4H, CH N), 3.60 m (20H,
1
3
1
-Benzyl-1-aza-18-crown-6 (IIc). Barium bro-
2
2
+
mide, 59 g (0.2 mol), was added to the aqueous phase;
CH O). Mass spectrum: m/z 263 [M] .
2
reaction time 15 h. Yield 74%, bp 190–193°C
1
(
0.05 mm). H NMR spectrum (CDCl ), δ, ppm: 2.59 t
1-Aza-21-crown-7. bp 125–134°C (0.05 mm).
3
1
(
4H, CH N), 3.51 m (22H, CH O, CH Ph), 7.08 s (5H,
H NMR spectrum (CDCl
N), 3.56 m (24H, CH
2
3
), δ, ppm: 2.39 m (1H, NH),
2
2
2
+
C H ). Mass spectrum: m/z 353 [M] .
2.59 t (4H, CH
trum: m/z 307 [M] .
2
O). Mass spec-
6
5
+
1
-Benzyl-1-aza-21-crown-7 (IId). Cesium chlo-
ride, 84 g (0.5 mol), was added to the aqueous phase;
reaction time 15 h. Yield 58%, bp 205–208°C
8,9-Benzo-1-aza-15-crown-5. mp 148–149°C;
published data [6]: mp 142–143°C. H NMR spectrum
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

1
352
LUK’YANENKO et al.
(
(
2
CDCl ), δ, ppm: 2.73 m (5H, NH, CH N), 3.80 t
9. Gokel, G.W., Dishong, D.M., Schultz, R.A., and
Gatto, V.J., Synthesis, 1982, p. 997.
0. Maeda, H., Nakatsuji, Y., and Okahara, M., Tetrahedron
3
2
12H, CH O), 6.80 s (4H, C H ). Mass spectrum: m/z
2 6 4
+
1
67 [M] .
Lett., 1981, vol. 22, p. 4105.
1
1. Calverly, M.J. and Dale, J., J. Chem. Soc., Chem.
REFERENCES
Commun., 1981, p. 684.
1
2. Bogatsky, A.V., Lukyanenko, N.G., Basok, S.S., and
Ostrovskaya, L.K., Synthesis, 1984, p. 138; Lukyanen-
ko, N.G., Basok, S.S., and Filonova, L.K., J. Chem.
Soc., Perkin Trans. 1, 1988, p. 3141; Lukyanenko, N.G.,
Basok, S.S., and Filonova, L.K., Synthesis, 1988,
p. 335; Luk’yanenko, N.G., Basok, S.S., and Filono-
va, L.K., Zh. Org. Khim., 1988, vol. 24, p. 1731.
3. Dale, J. and Kristiansen, P.O., Acta Chem. Scand., 1972,
vol. 26, p. 1471; Ouchi, M., Inoue, Y., Kanzaki, T., and
Hakushi, T., J. Org. Chem., 1984, vol. 49, p. 1408.
1
. Lukyanenko, N.G., Pastushok, V.N., Bordunov, A.V.,
Vetrogon, V.I., Vetrogon, N.I., and Bradshow, J.S.,
J. Chem. Soc., Perkin Trans. 1, 1994, p. 1489; Boila-
Gockel, A. and Junek, H., J. Prakt. Chem., 1999,
vol. 341, p. 20; Habata, Y., Saeki, T., Akabori, S.,
Zhang, X.X., and Bradshow, J.S., J. Heterocycl. Chem.,
2
001, vol. 38, p. 253; Sancenon, F., Martinez-Manez, R.,
1
1
Miranda, M.A., Segui, M.-J., and Soto, J., Angew. Chem.,
Int. Ed., 2003, vol. 42, p. 647; Tanaka, M., Kamada, K.,
Ando, H., Kitagaki, T., Shibutani, Y., and Kimura, K.,
J. Org. Chem., 2000, vol. 65, p. 4342; Luk’yanen-
ko, N.G., Basok, S.S., Kulygina, E.Yu., and Vetro-
gon, V.I., Russ. J. Gen. Chem., 2003, vol. 73, p. 1919.
4. Bailey, D., Tirrell, D., and Vogl, O., J. Macromol. Sci.,
Part A: Chem., 1978, vol. 12, p. 661.
15. Krakowiak, K.E., Bradshaw, J.S., and Zamecka-
Krakowiak, D.J., Chem. Rev., 1989, vol. 89, p. 929.
2
3
4
. Maeda, H., Nakatsuji, Y., and Okahara, M., J. Chem.
Soc., Chem. Commun., 1981, p. 471.
16. Fedorova, O.A., Vedernikov, A.I., Baranova, I.E.,
Eshcheulova, O.V., Fedorchuk, E.A., Gloe, K., and
Gromov, S.P., Izv. Ross. Akad. Nauk, Ser. Khim., 2004,
p. 381.
7. Yanovskaya, L.A. and Yufit, S.S., Organicheskii sintez v
dvukhfaznykh sistemakh (Organic Synthesis in Two-
Phase Systems), Moscow: Khimiya, 1982; Dehm-
low, E.V. and Dehmlow, S.S., Phase-Transfer
Catalysis, Weinheim: Chemie, 1983, 2nd ed.
8. Bousher, B.R. and Rest, A.J., J. Chem. Soc., Dalton
Trans., 1981, p. 1157.
19. Gokel, G.W. and Garcia, B.J., Tetrahedron Lett., 1977,
vol. 18, p. 317.
0. Calverly, M.J. and Dale, J., Acta Chem. Scand., Ser. B,
. Johnson, M.R., Sutherland, I.O., and Newton, R.F.,
J. Chem. Soc., Perkin Trans. 1, 1979, p. 357.
. Schultz, R.A., White, B.D., Dishong, D.M., Arnold, K.A.,
and Gokel, G.W., J. Am. Chem Soc., 1985, vol. 107,
p. 6659.
1
5
6
7
. Kuo, P.-L., Miki, M., Ikeda, I., and Okahara, M., J. Am.
Oil Chem. Soc., 1980, vol. 57, p. 227.
. Hogberg, S.A.J. and Cram, D.J., J. Org. Chem., 1975,
vol. 40, p. 151.
1
. Johnson, M.R., Jones, N.F., Sutherland, I.O., and
Newton, R.F., J. Chem. Soc., Perkin Trans. 1, 1985,
p. 1637.
2
8
. Greene, R.N., Tetrahedron Lett., 1972, vol. 13, p. 1793.
1981, vol. 36, p. 241.
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