Convenient method for preparation of aza-crown ethers

Article abstract of DOI:10.1080/00397910600588991

A convenient method for the preparation of peraza crown ethers in a one-pot synthesis in the presence of KF/Al₂O₃ is presented. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600588991

Synthetic Communicationsw, 36: 1569–1573, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600588991
Convenient Method for Preparation of
Aza-Crown Ethers
˘
˘
Gabriela Blani¸ta, Monica Bucs¸a, and Mircea Vlassa
Babes¸-Bolyai University, Faculty of Chemistry and Chemical Engineering,
Department of Organic Chemistry, Cluj-Napoca, Romania
Abstract: A convenient method for the preparation of peraza crown ethers in a one-pot
synthesis in the presence of KF/Al2O3 is presented.
Keywords: Aza-crown compounds, cyclization reactions, solid-supported reagent
Macrocyclic ligands containing heteroatoms are complexing agents for ionic
and neutral molecules. The aza-crown macrocycles play an important role in
this field, as demonstrated by the fact that half of all synthetic macrocycles
belong to this class. The special interest in the crown ether class is
explained by a much stronger association of the nitrogen atoms as
compared to the oxygen ones, due to a less electronegative force of
nitrogen, which implies more availability of the electronic pair for
complexation.
The peraza-crown macrocycles are the largest group of crown-ether
compounds and provide binding sites for transition-metal and other heavy-
metal ions. These compounds can be obtained by two general methods,
namely ring closure to form a bis Schiff base or ring closure to form
carbon-nitrogen single bonds.[1] The reaction of a sulfonamide with a
dihalide or a ditosilate ester belonging to the second method of general
Received in Poland October 21, 2005
Address correspondence to Mircea Vlassa, Babes¸-Bolyai University, Faculty of
Chemistry and Chemical Engineering, Department of Organic Chemistry, 11 Arany
Janos str., Cluj-Napoca, 400028; Romania. Fax: 040-0268-590818; E-mail: mvlasa@
chem.ubbcluj.ro
1569

˘ ˘
G. Blanit¸a, M. Bucs¸a, and M. Vlassa
1570
synthetic procedures is one of the most attractive ways to obtain this type of
crown ether. This method allows the preparation of peraza-crowns of different
sizes and number of nitrogen atoms.[2]
The Richman–Atkins process[2f,2g] has been used to prepare a large
variety of peraza-crowns. The first step of this reaction consists in the prep-
aration of bissulfonamide sodium salt under an inert atmosphere, followed
by cyclization of this salt with sulfonate ester (especially ditosylate ester)
leaving groups in a dipolar aprotic solvent (DMF), obviating the high-
dilution technique of the Stetter and Ross procedure.[2a]
We tried to obtain the afore mentioned compounds in a one-pot synthesis,
avoiding the preparation of bissulfonamide sodium salt under inert atmos-
phere. With that purpose in view, we achieved the reaction between
bissulfonamide and ditosylate in the presence of the solid-supported reagent
KF/Al2O3 by taking advantage of its strongly basic nature,[3] according to
Scheme 1.
The results of our experiments are shown in Table 1. A few solvents were
tested (ethanol, a mixture of acetonitrile-THF, acetonitrile). The best yields
were obtained in acetonitrile.
Scheme 1.

Method for Preparation of Aza-Crown Ethers
1571
Table 1. Peraza-crown ethers obtained in the presence of the solid-supported reagent
KF/Al2O3
Melting points (8C)
Recrystallization
solvent
Compound
Yield (%)
Found
Lit.
1
2
3
4
5
6
7
75
70
57
80
61
62
50
222
208
222–223[2g]
206[5]
—
Ethanol
Chloroform
Ethanol
210
234
234–236[2g]
294[4]
Ethanol þ chloroform
Toluene
Ethanol
296
204
201[6]
183–184 [2g]
182–183
Ethanol
In conclusion,
. We succeeded in obtaining peraza crown ethers in a one-pot synthesis with
good yields;
. The preparation of bissulfonamide sodium salts was eliminated and so the
running of the reaction under an inert atmosphere as required by the
Richman procedure was avoided; and
. Our method seems to be applicable to small- and medium-sized peraza-
crown ethers. The use of the solid-supported reagent KF/Al2O3 in the
case of peraza-crown ethers preparation is more advantageous than the
synthesis of crown ethers from polyethylene glycol and polyethylene
glycol ditosylates.[7]
EXPERIMENTAL
Materials
The melting points are uncorrected. The KF and basic Al2O3 were obtained
from Merck. Solvents were used as purchased. The RMN spectra were
recorded on a Varian Gemini 300 spectrometer in CD3OD with tetramethylsi-
lane as an internal reference. The K2O/Al2O3 solid-supported reagent was
prepared according to literature data.[8] The ditosyl derivatives of 1,2-ethyl
and 1,3-propyl diol were prepared according to the literature data.[9] The tosy-
lation of diethyltriamine and tetraethylpentaamine was achieved by using the
method of Koyama and Yoshino.[10] The tosylation of amino diols
were performed using the method of Bazzicalupi and coworkers.[11] N,N0-
(Methyliminodiethylene)bisphthalimide was obtained by the procedure
indicated by Searle and coworkers.[12]

˘ ˘
G. Blanit¸a, M. Bucs¸a, and M. Vlassa
1572
Typical Procedure
The N-tosyl polyamine (0.5 mmol), corresponding tosyl-diol or tosyl amino
diol (0.5 mmol), and KF/Al2O3 solid-supported reagent (2.5 g) were added
to acetonitrile (20 mL), and the mixture was stirred and refluxed for 24 h.
Then the reaction mixture was cooled, filtered from the solid support, and
recrystallized from the suitable solvent (see Table 1).
4-Methyl-1,7-ditosyl-1,4,7-triazacyclodecane (3). Anal. calcd. for
C22H31O4N3S2: C, 56.96; H 6.71; N, 9.02 (456.6). Found: C, 57.10; H,
6.80; N, 9.20. H1 NMR (300 MHz, CD3OD): d ¼ 1.53 (quintet, 2H), 2.27
(s, 3H N-Me), 2.35 (s, 6H, Me), 2.16 (t, 4H), 3.26 (t, overlap, 4H), 3.48
(t, overlap, 4H), 7.34 (d, 4H), 7.81 (d, 4H). 13C NMR (300 MHz, CD3OD):
d ¼ 24.3, 26.8, 42.5, 43.1, 44.8, 54.4, 127.2, 129.4, 141.6, 146.7.
ACKNOWLEDGMENT
˘
We thank MEdC (Ministerul Educa¸tiei s¸i Cercetarii) for the financial support
(grant CERES no. 54/2002).
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