Synthesis of novel chiral calix[4]crown: Lariat calix[4]-1,3-aza-crown with chiral amino acid group as branched chain

Article abstract of DOI:10.2174/157017811795685009

The novel lariat calix[4]-1,3-aza-crowns with chiral amino acids groups as branched chain (5a) and (5b) were synthesized via "1+1" addition of calix[4]-1,3-substituted benzaldehyde derivative (4) and amino acids hydrazide derivatives (3a) and (3b) in yields of 70% and 75%, respectively.

Full text of DOI:10.2174/157017811795685009

358
Letters in Organic Chemistry, 2011, 8, 358-360
Synthesis of Novel Chiral Calix[4]crown: Lariat Calix[4]-1,3-aza-crown
with Chiral Amino Acid Group as Branched Chain
Fafu Yang*,1,2, Biqiong Hong1, Hongyu Guo1, Zhisheng Huang1 and Xiaoyi Zhang1
1College of Chemistry and Materials Science, Fujian Normal University, Fuzhou 350007, P. R. China
2Fujian Key Laboratory of Polymer Materials, Fuzhou 350007, P.R. China
Received August 10, 2009: Revised July 16, 2010: Accepted March 25, 2011
Abstract: The novel lariat calix[4]-1,3-aza-crowns with chiral amino acids groups as branched chain (5a) and (5b) were
synthesized via “1+1” addition of calix[4]-1,3-substituted benzaldehyde derivative (4) and amino acids hydrazide
derivatives (3a) and (3b) in yields of 70% and 75%, respectively.
Keywords: Calix[4]crown, chiral, amino acid, aza, lariat.
Calixarenes are important supramolecular building
blocks, which can be modified by introducing suitable
functional groups and/or structural groups to create novel
receptors for specific guest molecules [1, 2]. Among all
kinds of calixarene derivatives, chiral calixarene
derivatives played important roles due to the potential
application in enantio discrimination processes [3-5]. To
obtain chiral calixarenes, the introduction of chiral units on
calix up-rim or low-rim was carried out extensively.
Therefore, a large number of chiral calixarenes containing
chiral functional groups, such as amino acids [6], amino
alcohol [7], peptides [8], alkaloids [9], chiral amines [10],
pinene-like units [11], glycidyl [12], guanidinium groups
[13], were reported in recent years. On the other hand,
some chiral calix[4]crown were prepared by using chiral
spacers as bridging chains, such as binaphthyl amine [11],
diphenyl amine [14], dinaphthol ether [5, 15], and
glucoside [16]. In this paper, we wish to report the facile
synthesis of novel chiral calix[4]crown: the lariat calix[4]-
1,3-aza-crown with chiral amino acid group as branched
chain.
conveniently by crystallization in CHCl3-MeOH in yields of
70% and 75%, respectively. It was interesting that no Schiff
bases (containing C=N bonds) condensating product was
obtained in this reaction condition under all kinds of mol ratio
of compounds (4) and (3). If these reactions were performed
under refluxing condition, the reaction results became
complicated and no purified compound was separated
successfully. In order to obtain Schiff-bases condensating
product, compound (1) was reacted with compound (4)
directly, but no condensating product was detected under all
kinds of reaction condition, which might be attributed to the
low reaction activities of amino groups in compound (1). To
the best of our knowledge, compounds (5a) and (5b) were the
first examples of chiral calix[4]crowns with chiral amino acid
groups as branched chain.
The structures and conformations of novel chiral
calix[4]arenes (5a) and (5b) were characterized by ESI-MS
1
spectra, IR spectra, H NMR spectra and elemental analyses.
The ESI-MS spectra of compounds (5a) and (5b) clearly
showed molecular base peak at 1282.0 (MK+) and 1243.3
(M+), respectively, indicating “1+1” intermolecular addition,
but not the Schiff-bases condensation. This deduction was also
supported by the IR spectra of (5a) and (5b). The C=O
absorption peak of compound (4) at 1694cm-1 disappeared, but
The synthetic route is shown in Fig. (1). Amino acids
derivatives (1a) and (1b) were prepared by esterification of
L-leucine and L-isoleucine. Reacting compounds (1a) and
(1b) with p-toluene sulfonyl chloride afforded compounds
(2a) and (2b). Then by ammonolysis of compounds (2a)
and (2b) with hydrazine hydrate, amino acids hydrazide
derivatives (3a) and (3b) were synthesized in ideal yields
[17]. On the other hand, calix[4]-1,3-substituted benzal-
dehyde derivative (4) was obtained by reacting p-tert-
butylcalix[4]arene with p-tosyloxyethoxyl- benzaldehyde
(mol ratio = 1:2) in K2CO3 / MeCN system for 48 h [18].
By stirring compound (4) with (3a) or (3b) in CHCl3-EtOH
(V:V=1:1) under room temperature, novel chiral
calix[4]crowns (5a) and (5b) were prepared via “1+1”
addition mode. Compounds (5a) and (5b) were purified
1
no C=N (Schiff-bases) absorption peak appeared. In the H
NMR spectra of compounds (5a) and (5b), all 1H NMR signals
were assigned to protons properly. Two singlets (1:1) for the
tert-butyl groups, one AB system for the methylene bridges of
the calix[4]arene skeleton suggested that calix[4]arene moiety
adopted the cone conformation [9-11]. These novel chiral
calix[4]crowns (5a) and (5b) were expected to exhibit
enantiomer recognition capabilities, which are under
investigation currently.
GENERAL PROCEDURE FOR THE PREPARATION
OF NOVEL CHIRAL CALIX[4]CROWNS (5A) AND (5B)
Under N2 atmosphere, the mixture of compound (4) (1
mmol, 0.94g) and amino acids derivatives (3a) or (3b) (1.1
mmol, 0.33g) was stirred in 40 mL CHCl3-EtOH (V:V=1:1) at
room temperature for 24 h. TLC detection showed the
*Address correspondence to this author at the College of Chemistry and
Materials Science, Fujian Normal University, Fuzhou 350007, P. R.
China; Tel: 0086-591-83465225: Fax: 0086-591-83465225:
E-mail: yangfafu@fjnu.edu.cn
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers Ltd.

Synthesis of Novel Chiral Calix[4]crown
Letters in Organic Chemistry, 2011, Vol. 8, No. 5
359
R
R
R
R
H
SOCl2
H
NH2NH2
TsCl
H
NH2
H
N
Ts
NH2 HCl
H
NH2
COOH
H
N
Ts
MeOH
pyridine
COOCH3
CONHNH2
COOCH3
3
2
1
R
O
S
H
H
N
CH3
O
O
CHO
CHO
HN
N
CHO
HOHC
CHOH
OH
3
CH3
O
O
5a: R =
5b: R =
O
OTs
CH3
CH3
O
CH3
O
OH
OH
O
O
4
K2CO3, MeCN
Bu-t
O
O
OH
OH
t-Bu
Bu-t
Bu-t
t-Bu
t-Bu
Bu-t
4
Bu-t
t-Bu
[ no C=N bonds formed ]
5
Fig. (1).
ACKNOWLEDGEMENTS
disappearance of materials. After distilling off the solvent
under reduced pressure at room temperature, the residue
was treated with 15 mL MeOH. The yellow precipitation
was then separated out. The precipitation was
Financial support from the National Natural Science
Foundation of China (No. 20402002) and Fujian Natural
Science Foundation of China (No. 2009J01019) is greatly
acknowledged and Program for Excellent young researchers in
University of Fujian Province (JA10056).
recrystallized
by
CHCl3-MeOH;
novel
chiral
calix[4]crowns (5a) and (5b) were then obtained in the
yields of 70% and 75%, respectively. Compound (5a):
m.p. 243-245oC; [ꢀ]D = + 3.7 (c 0.20, CHCl3); 1H NMR
27
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