Synthesis of two-armed macrocycles via N,N′-disubstituted ω,ω′-diaminoether precursors

Article abstract of DOI:10.1135/cccc19960622

N,N′-Dialkyldiazacrowns and their precursors, bis(alkylamino) derivatives of tri- and tetraethylene glycols, are synthesized and characterized.

Full text of DOI:10.1135/cccc19960622

622
Hosgoren, Karakaplan, Togrul:
SYNTHESIS OF TWO-ARMED MACROCYCLES VIA N,N′-DISUBSTITUTED
ω,ω′-DIAMINOETHER PRECURSORS
Halil HOSGOREN, Mehmet KARAKAPLAN and Mahmut TOGRUL
Department of Chemistry,
Faculty of Arts and Sciences, University of Dicle, 21280 Diyarbak1r, Turkey
Received November 28, 1994
Accepted December 15, 1995
N,N′-Dialkyldiazacrowns and their precursors, bis(alkylamino) derivatives of tri- and tetraethylene
glycols, are synthesized and characterized.
Key words: Diazacrowns; Oligoethylene glycols, derivatives.
Crown ethers were first described by Pedersen1. Since that time the chemistry of these
neutral complexing agents has undergone a rapid development. Besides the monocyclic
compounds, a large number of oligo- and polycyclic derivatives have been synthesized
and studied2. For many of those preparations, oligo(oxoethylenes) with amino end
groups have been used as intermediates because the nitrogen atoms allow further con-
trolled reaction during the synthesis3. In the resultant complexing molecules the ni-
trogen atoms are electron donor atoms as well as branching points.
The azacrowns possess complexation properties that are intermediate between those
of the all-oxygen crowns, which strongly complex alkali and alkaline-earth metal ions,
and those of the all-nitrogen cyclams, which strongly complex heavy metal cations.
These mixed complexation properties make the azacrowns interesting for research in
many areas. The azacrowns have important uses as synthetic receptors in molecular
recognition processes1 and, in some cases, their anion complexation properties are simi-
lar to those in certain biological systems4–6. They show an enhanced complexing ability
for ammonium salts7,8 and for transition-metal ions7,9 over the all-oxygen crown com-
pounds. Anion-promoted two-phase reactions can be successfully performed by using
as catalysts crown ethers of suitable structure which continuously transfer the anion
from the aqueous to organic phase10.
For this reason we have prepared a series of diazacrowns 2 substituted with long
alkyl chains. The synthesis of bis(secondary amine) precursors derived from oligoe-
thylene glycols is illustrated in Scheme 1. This alkylation procedure, originally de-
veloped by Krespan11 is more straightforward than the synthesis by other methods12–16
.
Some of these compounds were obtained previously and tested as drugs17,18, pes-
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623
ticides19 and extraction agents for mercury(II) chloride, alkali metals and alkaline earth
metals12.
RNH
2
(
)
m
(
)
m
R
N
H
O
O
N R
H
Cl
O
O
Cl
m R
1
1
1
1
2
heptyl
octyl
1a
1b
1c
1d
1e
nonyl
dodecyl
benzyl
SCHEME 1
In previous studies10,12,20,21, most of N,N′-dialkyl derivatives of 1,10-diaza-18-crown-6
such as butyl, hexyl, octyl, dodecyl and benzyl ones were synthesized by alkylation or
acylation of ring nitrogen atoms using the expensive diazacrown.
In this study all N,N′-dialkyl derivatives of 1,10-diaza-18-crown-6 were synthesized
by reaction of triethylene glycol ditosylate and an appropriate diazadioxaalkane. This
cyclization is illustrated in Scheme 2.
1
2
O
O
O
3
4
R
N
H
O
O
O
O
N
H
R
Na CO
2
3
N
CH (CH ) CH
CH (CH ) CH
N
2
2
2 m
3
3
2 m
MeCN + THF
TsO
OTs
O
m
5
2a
2b
7
6
SCHEME 2
2c
2d
10
EXPERIMENTAL
Infrared spectra were recorded on a Midac 1700 instrument in KBr pellets. 1H and 13C NMR spectra
at 200 and 50.2 MHz, respectively, were recorded on a Bruker-AC spectrometer in CDCl3 and are
reported in ppm (δ) downfield from internal tetramethylsilane. Elemental analyses were performed on
a Carlo–Erba model 1200 instrument. All reactions were performed under dry nitrogen atmosphere.
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Hosgoren, Karakaplan, Togrul:
Azaoxaalkanes 1a–1e
A solution of amine and 1,2-bis(2-chloroethoxy)ethane or related dichloro derivative (mole ratio 4 : 1)
was heated and stirred at 140–160 °C under nitrogen atmosphere for 4 h. The reaction mixture was
then dissolved in hot benzene and the starting amine salt precipitated was filtered off. The filtrate
was extracted with 10% aqueous sodium hydroxide. The benzene extracts were dried with anhydrous
TABLE I
Characteristics of dipicrates of azaoxaalkanes 1a–1e
Calculated/Found
B.p.a, °C/kPa
Yield, %
Formula
(M.w.)
Compound
M.p., °C
% C
% H
% N
1a
1b
1c
1d
1e
180–182/0.02
46
95–97
C32H50N8O16
(802.8)
47.90
48.03
6.27
6.04
13.95
13.39
194–201/0.11b
46
99–103 C34H54N8O16
(830.8)
49.15
49.53
6.55
6.73
13.49
14.02
208–209/0.04
32
101–103 C36H58N8O16
(858.9)
50.34
50.52
6.80
7.08
13.04
13.00
254–258/0.07c
46
102–104 C42H70N8O16
(943.1)
53.50
53.49
7.48
7.57
11.88
11.55
d
230–237/0.12
43
174–176d C22H34Cl2N2O3
(445.4)
59.32
59.62
7.69
7.63
6.25
6.05
b
c
d
a Free base. 167 °C/0.002 kPa (ref.12). M.p. 38–39 °C (refs12,14). Dihydrochloride.
TABLE II
Characteristics of 1,10-dialkyl-1,10-diaza-18-crowns-6
Calculated/Found
M.p., °C
Yield, %
Formula
(M.w.)
Compound
% C
% H
% N
a
2a
2b
–
C26H54N2O4 . Ba(ClO4)2 . H2Ob
(812.9)
38.42
38.67
6.94
7.24
3.45
3.44
30c
–6d
30f
C30H62N2O4 . Ba(ClO4)2 . H2Oe
(869.1)
41.46
41.94
7.42
7.52
3.22
3.00
a
b
c
d
e
f
B.p. 274–280 °C/0.09 kPa. M.p. 156–159 °C. Crude yield. Oil20. M.p. 104–106 °C. After
chromatography.
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625
sodium sulfate, filtered, and the solvent was evaporated. Unreacted excess of amine was recovered
and the product distilled. The azadioxaalkanes 1a–1e were characterized by their dipicrates (Table I).
1,10-Dialkyl-1,10-diaza-18-crowns-6 2a–2d
A mixture of 0.048 mol of 1, 0.048 mol of triethylene glycol ditosylate, and 0.173 mol of Na2CO3 in
MeCN–THF (800 : 200 ml) was heated at reflux under nitrogen atmosphere for 24 h. The reaction
mixture was cooled, filtered, and concentrated in vacuo. Column chromatography (alumina, 2%
1-propanol–hexane) followed by a bulb-to-bulb distillation gave 2a and 2b as transparent oils from
which crystalline barium perchlorate complexes were prepared (see Table II). Column chromatography
(alumina, 2% 1-propanol–hexane) followed by recrystallization from diethyl ether gave crystalline 2c
(25%, m.p. 29–32 °C) and 2d (27%, m.p. 50–52 °C), with physical properties identical with those
reported20,21
.
2a. Ba(ClO4)2 . H2O. IR spectrum: 3 438 (O–H); 2 955, 2 926, 2 857 (C–H); 1 117, 1 091, 1 061
1
(C–O). H NMR spectrum: 0.87 t, 6 H (CH3); 1.28 s, 16 H (CH2); 1.8 bs, 2 H (H2O); 2.66–3.10 m,
12 H (NCH2, OCCH2N); 3.40–4.02 m, 16 H (OCH2). 13C NMR spectrum: 14.53 (CH3); 23.03, 27.63,
27.67, 29.70, 32.22, 52.00 (C-4); 52.08 (C-3); 69.00 (C-2); 70.48 (C-1).
2b. Ba(ClO4)2 . H2O. IR spectrum: 3 551, 3 479 (O–H); 2 994, 2 849 (C–H); 1 140, 1 064, 1 105
(C–O). 1H NMR spectrum: 0.86 t, 6 H (CH3); 1.24 s, 28 H (CH2); 2.18 bs, 2 H (H2O); 2.6–3.5 m,
12 H (NCH2, OCCH2N); 3.4–3.8 m, 16 H (OCH2). 13C NMR spectrum: 14.60 (CH3); 23.14, 27.71,
29.73, 30.01, 32.35, 51.97 (C-4); 52.09 (C-3); 68.97 (C-2); 70.48 (C-1).
RESULTS AND DISCUSSION
In this study some new azaoxaalkanes 1a–1e were synthesized and characterized by
their picrates or dihydrochlorides (Table I). The chosen synthesis procedure is more
straightforward than the other synthetic methods. Also, this procedure gives the corres-
ponding diazacrowns as by-products (their isolation is not given in this study). For
example, the synthesis of 1a gave 16% of 2a as a by-product. Other synthesis methods
described in literature required protection of secondary amine with benzyl blocking
group and decreasing the nucleophilic strength of primary amine by tosyl substitution.
Removing the benzyl and tosyl groups required additional reaction steps and complex
procedures. The reaction of azaoxaalkane precursors, triethylene glycol ditosylate and
Na2CO3 in MeCN–THF gave the diazacrowns with the physical properties identical
with those reported.
We thank TÜBITAK (Scientific and Technical Research Council of Turkey) for support of this work.
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