Enantioselective fluorescent sensors for chiral carboxylates based on BINOL - Synthesis and chiral recognition

Article abstract of DOI:10.1139/V10-001

The four novel derivatives of 1,1′-bi-2-naphthol (BINOL) have been prepared, and the structures of these compounds have been characterized by IR, MS, ¹H and ¹³C NMR spectroscopy, and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and ¹H NMR spectroscopy. The receptors exhibited different chiral-recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between host and guest. The receptors exhibit excellent enantioselective fluorescent-recognition ability towards the amino acid derivatives.

Full text of DOI:10.1139/V10-001

367
Enantioselective fluorescent sensors for chiral
carboxylates based on BINOL — Synthesis and
chiral recognition
Kuo-xi Xu, Yu-xia Wang, Shu-yan Jiao, Jin Zhao, and Chao-jie Wang
Abstract: The four novel derivatives of 1,1’-bi-2-naphthol (BINOL) have been prepared, and the structures of these com-
1
pounds have been characterized by IR, MS, H and 13C NMR spectroscopy, and elemental analysis. The enantioselective
1
recognition of these receptors has been studied by fluorescence titration and H NMR spectroscopy. The receptors exhib-
ited different chiral-recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between
host and guest. The receptors exhibit excellent enantioselective fluorescent-recognition ability towards the amino acid de-
rivatives.
Key words: receptor, fluorescence, enantioselective recognition, anions, NMR spectroscopy.
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Resume : On a prepare quatre nouveaux derives du BINOL et on en a determine les structures par analyse elementaire et
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par spectroscopies infrarouge, de masse et RMN du H et du C. On a etudie les proprietes de reconnaissance enantiose-
lective de ces recepteurs par titrage de fluorescence et par spectroscopie RMN du H. Les recepteurs presentent diverses
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capacites a reconnaıtre la chiralite de quelques enantiomeres de produits chiraux et ils forment des complexes 1:1 entre
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molecules hotes et invitees. Les recepteurs presentent une capacite excellente de reconnaıtre une fluorescence enantioselec-
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tive vis-a-vis des derives d’acides amines.
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Mots-cles : recepteur, fluorescence, reconnaissance enantioselective, anions, spectroscopie RMN.
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[Traduit par la Redaction]
response to the enantiomers in the recognition interaction,
which may offer a simple method to explore the recognition
process for more information. The binaphthyl unit was espe-
cially eye-catching for its stable chiral configuration and
tunable dihedral angle between the two naphthalene rings.
Over the last two decades, binaphthyl derivatives have been
shown to exhibit excellent enantioselectivities and turnovers
in several types of asymmetric reactions, often matching the
enantioselectivities traditionally regarded as being reserved
for the enzyme realm.6 As a naturally occurring chiral
source, amino acids generally exhibit biological activity,
and their recognition, in particular chiral recognition, attracts
considerable interest.7 Furthermore, they can be easily modi-
fied at the amino and carboxylic groups, which can also act
as binding sites to form coordinate bonds with chiral mole-
cules, so they were often used in the design and synthesis of
artificial chiral receptors,8 such as different types of acyclic
compounds9 as host molecules. We chose several familiar
amino acids (e.g., alanine, phenylalanine) as chiral building
blocks and introduced them into the 1,1’-bi-2-naphthol
(BINOL) framework to construct the fluorescent receptors
(Scheme 1). Herein, we describe the development of BINOL
Introduction
Molecular recognition, and in particular chiral recogni-
tion, is a fundamental characteristic in the biochemical sys-
tems. The study of synthetic model systems could contribute
to the understanding of these processes and, at the same
time, offer new perspectives for the development of pharma-
ceuticals, enantioselective sensors, catalysts, and other mo-
lecular devices.1 The basis of any chiral recognition event is
the formation of diastereomeric complexes composed of a
chiral receptor and a chiral substrate possessing different
stabilities.2 The crucial points in the molecular design of
chemosensors are how to achieve the specific recognition of
a certain molecule and how to transduce the recognition
event into a signal.3 Many efforts involve the covalent link-
ing of an optical signaling unit (a chromophore or a fluoro-
phore) to a specific receptor for the chiral molecuales.4
Compared with other detection methods, such as NMR,
HPLC, CD, or capillary electrophoresis, fluorescence techni-
ques have often been used to study the interaction between
enantiomers and receptors because of their sensitivity, selec-
tivity, and versatility.5 On the basis of their respective ad-
vantages, we attempt to design some receptors with optical
Received 30 July 2009. Accepted 7 December 2009. Published on the NRC Research Press Web site at canjchem.nrc.ca on 11 March
2010.
K.-x. Xu and Y.-x. Wang. College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China; Key Lab of
Natural Medicinal and Immunal Engineering, Henan University, Kaifeng 475004, China.
S.-y. Jiao. College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China.
J. Zhao and C.-j. Wang.1 Key Lab of Natural Medicinal and Immunal Engineering, Henan University, Kaifeng 475004, China.
1Corresponding author (e-mail: wcjsxq@henu.edu.cn).
Can. J. Chem. 88: 367–374 (2010)
doi:10.1139/V10-001
Published by NRC Research Press

368
Can. J. Chem. Vol. 88, 2010
Fig. 1. Structures of the receptors R-1, S-5, and R-5.
Scheme 1. Synthesis of the receptor S-1.
derivatives bearing amino acid units, and their bonding
properties with some enantiomers of chiral materials have
been examined by using fluorescence titration experiments
in CHCl3. Receptors exhibited good enantioselective recog-
nition abilities towards chiral materials and formed 1:1 com-
plex with the guests in CHCl3. 1H NMR experiments
suggested that hydrogen-bonding interactions between the
host and guest were the main factor in the recognition proc-
ess.
Results and discussion
Synthesis
The synthesis of receptor S-1 is outlined in Scheme 1.
The starting materials binaphthyl dialdehydes were prepared
from BINOL.10 N-Boc-protected alanine methyl ester (2)
were synthesized according to the literature with high
yield,11 and then reacted with excess amount of ethylenedi-
amine to obtain the compound (S)-tert-butyl-1-(2-aminoe-
thylamino)-1-oxopropan-2-ylcarbamate (3). To avoid the
partial racemization of 3 in this reaction, the compound 2
and ethylenediamine were dissolved in large amount of
methanol and stirring was continued at room temperature.
Especially at the end of reaction, the solvent and ethylenedi-
amine should be evaporated under high vacuum at about
30 8C, because a little higher temperature may lead the rac-
emization of compound. Condensation of S-binaphthyl dia-
ldehydes with compound 3, followed by reduction, afforded
the disubstituted BINOL S-1 (Scheme 1). To study how the
BINOL and amino acid units in S-1 influenced the enantio-
selective fluorescent recognition, R-1, S-5, and R-5 were
also prepared (Fig. 1). They are readily soluble in common
organic solvents, such as CHCl3, CH2Cl2, CH3OH, DMSO,
and DMF. The structures of all these compounds were char-
Fig. 2. Structures of the guests.
between the receptor and guest by hydrogen bondings.1c
We also chose two amino alcohols, namely, alaninol and
phenylalaninol, as guests to compare the associated abilities
of the hosts to bind with neutral molecules.
The fluorescence spectra were recorded from a solution of
sensor S-1 (1.22 ꢀ 10–5 mol L–1) in CHCl3 in the absence or
presence of various enantiomers, (R)-, (S)-Ala, and Phe
anions. Because there was almost no change observed on
the UV–vis spectra of receptors upon addition of the anions,
the interaction between host and anion was only evaluated
by fluorescent spectra.
Upon addition of (S)- or (R)-Ala or Phe anions, different
fluorescent-quenching degrees of S-1 were observed. The
quenching efficiencies of (S)-amino acid anions were much
higher than the (R)-amino acid anions. Figure 3 and Fig. 4
show the fluorescence emission spectra of a mixture of S-1
1
acterized by IR, MS, H and 13C NMR spectroscopy, and el-
emental analysis.
Fluorescence spectra study
The properties of the chiral recognition of receptors S-1
were investigated in the absence and presence of various chiral
carboxylates (Fig. 2), such as (S)- and (R)-mandelate, the a-
phenylglycine anion, N-Boc-protected alanine anion (Ala),
and N-Boc-protected phenylalanine anion (Phe), in which the
amino groups were protected by the tert-butyloxycarbonyl
functionality. In each case, tetrabutylammonium was used
as the counter cation, which could increase the reaction
Published by NRC Research Press

Xu et al.
369
Fig. 3. Fluorescence spectra of receptor S-1 (1.22 ꢀ 10–5 mol L–1)
with (S)-Ala anion in CHCl3. The anion equivalents are: 0, 2, 4, 6,
8, 10, 20, 40, 60, 80, 100, 150, 200, 300, and 500. lex = 278 nm.
Inset: changes in the fluorescence intensity of S-1 at 371 nm upon
addition of (S)-Ala anion. The line shown is a line-fitted curve. The
correlation coefficient (R) of the nonlinear curve fitting is 0.9994.
Fig. 4. Fluorescence spectra of receptor S-1 (1.22 ꢀ 10–5 mol L–1)
with (S)-Ala anion in CHCl3. The anion equivalents are: 0, 2, 4, 6,
8, 10, 20, 40, 60, 80, 100, 200, 300, 400, and 500. lex = 278 nm.
Inset: changes in the fluorescence intensity of S-1 at 371 nm upon
addition of (S)-Ala anion. The line shown is a line-fitted curve. The
correlation coefficient (R) of the nonlinear curve fitting is 0.9994.
and different concentrations of the (S)- or (R)-Ala anion in
CHCl3 (lex = 278 nm), respectively. The graphs in the top
right corners of Figs. 3 and 4 illustrate the fluorescence in-
tensity change of receptor S-1 upon addition of (S)- and (R)-
Ala anions, respectively. Figure 5 shows the different fluo-
rescence intensity changes when the same equiv. of (S)- or
(R)-Ala anion were added to the host S-1, the quenching ef-
ficiency was 46.7% when 4 equiv. of (S)-Ala anion was
added to the solution of S-1, while the quenching efficiency
was only 8.7% when 4 equiv. of (R)-Ala anion was added.
The quenched efficiencies (DIS/DIR = 5.37) indicated that
the host S-1 has a good enantioselective recognition ability
between the (S)- and (R)-Ala anions, respectively. Satisfac-
tory nonlinear curve fitting (the correlation coefficient is
over 0.99) confirmed that S-1 and the (S)- or (R)-Ala formed
a 1:1 complex (see the insets of Fig. 3 and Fig. 4). For a
complex of 1:1 stoichiometry, the association constant (Kass)
can be calculated by using eq. [1] from the Origin 7.5 soft-
ware package12,13
Fig. 5. Fluorescence spectra of host S-1 (2.13 ꢀ 10–6 mol L–1) with
4.0 equiv. of (S)- and (R)-Ala anion in CHCl3.
when (S)- or (R)-Phe anions were added into a solution of
S-1. The result of a nonlinear curve fitting (at 371 nm) indi-
cates that a 1:1 complex was formed between receptor S-1
and (S)- or (R)-Phe (see Table 1). In addition, the associa-
½1ꢁ
X ¼ X0 þ ðXlim ꢂ X0Þ=2C0fCH þ CG
2
1=2
þ 1=Kass ꢂ ½ðCH þ CG þ 1=KassÞ ꢂ 4CHCGꢁ
g
where X represents the fluorescence intensity, CH and CG are
the host and guest concentrations, respectively, and C0 is the
initial concentration of the host. The association constants
(Kass) and correlation coefficients (R) obtained by a non-
linear least squares analysis of X vs. CH and CG are listed in
Table 1.
tion constants (Kass) were different (see Table 1) (Kass(S)
=
=
(3.17 0.11) ꢀ 104 M–1, DG0 = –25.69 kJ mol–1; Kass(R)
(3.09 0.08) ꢀ 103 M–1, DG0 = –19.92 kJ mol–1), yielding
an S/R selectivity [Kass(S) /Kass(R)] of 10.26 for the Phe anions
and a DDG0 value of –5.77 kJ mol–1, demonstrating that S-1
has good chiral recognition ability towards the enantiomers
of Phe anions.
The association constant for the interaction of S-1 with
the (S)- and (R)-Ala anion is (3.60
0.27) ꢀ 104 and
(3.54 0.19) ꢀ 103 M–1, respectively. Receptor S-1 gives
an enantioselectivity Kass((S)-Ala) /Kass((R)-Ala) = 10.17. The dra-
matically different fluorescent responses and quenching effi-
ciencies observed for the two enantiomers indicate that S-1
has excellent enantioselective fluorescent-recognition ability
towards the Ala anion. Similar phenomena were observed
The binding of S-1 with mandelate and a-phenylglycine
anion was also carried out, and the association constants of the
host S-1 with mandelate and a-phenylglycine anion are also
listed in Table 1. When S-1 interacted with a-phenylglycine
anion, the receptor S-1 exhibited weak enantioselective
recognition ability to a-phenylglycine anion that have been
Published by NRC Research Press

370
Can. J. Chem. Vol. 88, 2010
Table 1. Association constants (Kass), correlation coefficients (R), enantioselectivities (Kass(S)/Kass(R)), Gibbs free energy changes (–DG0),
and DDG0 calculated from DG0 for the complexation of receptors S-1 and R-1 with S-/R- guests in CHCl3 at 25 8C.
Entry
1
2
3
4
5
6
7
8
Host
S-1
S-1
S-1
S-1
S-1
S-1
S-1
S-1
S-1
S-1
S-1
S-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
R-1
S-5
S-5
S-5
S-5
S-5
S-5
S-5
S-5
S-5
S-5
S-5
S-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
R-5
Guest
Kass (M–1)a,b
R
Kass(S)/Kass(R)
10.17
10.26
5.87
–DG0 (kJ mol–1)
26.01
20.26
25.69
19.92
27.2
DDG0 (kJ mol–1)
–5.75
–5.77
–4.27
–1.31
–1.1
(S)-Alac
(3.60 0.27)ꢀ104
(3.54 0.19)ꢀ103
(3.17 0.11)ꢀ104
(3.09 0.08)ꢀ103
(5.81 0.26)ꢀ104
(1.04 0.13)ꢀ104
(6.64 0.26)ꢀ104
(3.91 0.19)ꢀ104
(6.72 0.31)ꢀ102
(4.31 0.05)ꢀ102
(5.98 0.21)ꢀ102
0.9971
0.9984
0.9927
0.9928
0.9908
0.9946
0.9923
0.9931
0.9924
0.9902
0.9944
0.9919
0.9903
0.9912
0.9941
0.9937
0.9952
0.9917
0.9962
0.9933
0.9917
0.9951
0.9903
0.9927
0.9989
0.9946
0.9938
0.9913
0.9931
0.9911
0.9956
0.9931
0.9907
0.9916
0.9907
0.9921
0.9934
0.9940
0.9941
0.9913
0.9919
0.9934
0.9926
0.9915
0.9923
0.9908
0.9912
0.9903
(R)-Alac
(S)-Phec
(R)-Phec
(S)-Mandelate
(R)-Mandelate
(S)-Phenylglycine
(R)-Phenylglycine
(S)-Alaninol
(R)-Alaninol
(S)-Phenylalaninol
22.93
27.53
26.22
16.14
15.04
15.85
13.12
20.06
25.57
20.21
25.79
24.22
27.93
25.54
26.86
14.53
16.22
12.44
16.81
26.58
22.76
26.39
22.47
26.81
23.91
27.58
26.47
16.07
14.43
15.86
13.50
23.43
26.28
22.78
26.27
24.54
26.73
26.26
27.39
14.87
15.86
13.72
15.75
1.70
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
1.56
(R)-Phenylalaninol (1.99 0.15)ꢀ102
3.01
–2.73
5.51
(S)-Alac
(3.26 0.22)ꢀ103
(3.02 0.13)ꢀ104
(3.47 0.26)ꢀ103
(3.29 0.24)ꢀ104
(1.75 0.11)ꢀ104
(7.81 0.51)ꢀ104
(2.98 0.22)ꢀ104
(5.07 0.19)ꢀ104
(3.51 0.14)ꢀ102
(6.94 0.29)ꢀ102
(1.51 0.07)ꢀ102
(R)-Alac
1/9.26
1/9.48
1/4.46
1/2.41
1/1.98
1/5.64
4.67
(S)-Phec
(R)-Phec
5.58
(S)-Mandelate
(R)-Mandelate
(S)-Phenylglycine
(R)-Phenylglycine
(S)-Alaninol
(R)-Alaninol
(S)-Phenylalaninol
3.71
1.34
1.69
(R)-Phenylalaninol (8.81 0.44)ꢀ102
4.37
(S)-Alac
(4.53 0.18)ꢀ104
(9.71 0.52)ꢀ103
(4.19 0.24)ꢀ104
(8.62 0.29)ꢀ103
(4.97 0.26)ꢀ104
(1.54 0.39)ꢀ104
(6.77 0.43)ꢀ104
(4.34 0.39)ꢀ104
(6.53 0.35)ꢀ102
(3.37 0.39)ꢀ102
(6.01 0.35)ꢀ102
(R)-Alac
–3.82
–3.92
–2.90
–1.11
–1.64
–2.36
2.85
(S)-Phec
(R)-Phec
4.86
(S)-Mandelate
(R)-Mandelate
(S)-Phenylglycine
(R)-Phenylglycine
(S)-Alaninol
(R)-Alaninol
(S)-Phenylalaninol
3.23
1.56
1.94
(R)-Phenylalaninol (2.32 0.39)ꢀ102
2.59
(S)-Alac
(1.27 0.10)ꢀ104
(4.02 0.18)ꢀ104
(9.78 0.41)ꢀ103
(3.99 0.22)ꢀ104
(1.99 0.26)ꢀ104
(4.82 0.39)ꢀ104
(3.98 0.43)ꢀ104
(6.27 0.39)ꢀ104
(4.03 0.35)ꢀ102
(5.99 0.39)ꢀ102
(2.53 0.35)ꢀ102
(R)-Alac
1/3.17
1/4.08
1/2.42
1/1.58
1/1.49
1/2.27
(S)-Phec
(R)-Phec
3.49
(S)-Mandelate
(R)-Mandelate
(S)-Phenylglycine
(R)-Phenylglycine
(S)-Alaninol
(R)-Alaninol
(S)-Phenylalaninol
2.19
1.13
0.99
(R)-Phenylalaninol (5.74 0.39)ꢀ102
2.03
aThe data were calculated from the results of fluorescence titrations in CHCl3.
bAll error values were obtained from nonlinear curve fitting.
cAla and Phe tetrabutylammonium salts, the amino group was protected by a tert-butyloxycarbonyl function.
tested (see Table 1). Upon the addition of alaninol or
phenylalaninol into a solution of in CHCl3, the fluorescence
intensity of S-1 was slightly quenched by both (S)- and (R)-
enantiomers (see Table 1). This indicates that hydrogen
bonding plays an important role in the interaction between
the host and guest and leads to the easier signal transduc-
tions of chiral recognition by fluorescence method.
The continuous variation methods were also employed to
determine the stoichiometric ratio of the receptor S-1 with
guests [(S)- and (R)-Ala anions]. The total concentration of
Published by NRC Research Press

Xu et al.
371
host and guest was constant (1.0 ꢀ 10–6 mol L–1) in CHCl3,
with a continuously variable molar fraction of host ([H]/([H]
+ [G])). Figure 6 shows the Job plots of receptor S-1 with
(S)- and (R)-Ala anion (at 371 nm, lex = 278 nm). When
the molar fraction of the host was 0.50, the fluorescence in-
tensity reached a maximum, which demonstrated that recep-
tor S-1 formed a 1:1 complex with (S)- and (R)-Ala anions,
respectively.14
Fig. 6. Job plots of receptor S-1 with (S)- and (R)-Ala anions
(367 nm, lex = 290 nm). The total concentration of the host [H] and
guest [G] is 1.0 ꢀ 10–6 mol L–1 in CHCl3. I0: fluorescence intensity
of S-1; I: fluorescence intensity of S-1 in the presence of the guest.
The decrease in fluorescence intensity of the excimer
upon addition of the anion is similar to the anion-induced
fluorescence decrease reported previously.15 Because of the
similar structure of S-1, the fluorescent variations of S-1
showed the same trend. Since there were no changes in the
UV–vis spectra of the receptors when treated with (S)- or
(R)-anions, a photoinduced electron transfer (PET) process
might be responsible for the fluorescent quenching.16 In the
absence of anions, PET between the binaphthyl unit and the
electron-withdrawing amide substituents might result in
quenched fluorescence. In the presence of guest anions, the
fluorescence quenching of receptors S-1 most likely arose
from the change of the free energy (DGPET) of the electron
transfer between the excited fluorophore and the receptor.17
Therefore, fluorescence quenching was observed.
To study how the chirality of the amino acid unit and
BINOL groups in S-1 influenced the enantioselective fluo-
rescent recognition, R-1, the diastereomeric compounds of
S-1, S-5, and R-5 were also prepared by similar methods.
We also studied its interaction with mandelate, phenylgly-
cine, Ala and Phe anions, alaninol, and phenylalaninol,
which showed the opposite enantioselectivity. That is, the
(R)-guest enantiomer quenched the fluorescence of R-1
more efficiently than (S)-guest. The result of fluorescence ti-
tration indicated that a matched chirality between the guest
anions center and the chiral BINOL unit led to the enantio-
selective recognition. The enantiomers of guest anions inter-
acted with R-1 and S-1 in the same fashion.
0.42 ppm, Fig. 7D) than that of the CH proton of the (R)-
enantiomer (from d = 3.85 to 4.19 ppm, Dd = 0.34 ppm,
Fig. 7E). Moreover, the signals of the –OH proton in the H
1
NMR spectra of the receptor S-1 become weakened obvi-
ously and have downfield shift from 6.57 to 6.78 ppm (Dd =
0.21 ppm, Fig. 7D) or 6.74 ppm (Dd = 0.17 ppm, Fig. 7E)
for (S)- or (R)-Ala anion, respectively, while the signals of
the peaks of binaphthyl fragments are downfield-shifted and
broadened with the addition of the guest. The signal of the
amide (NH) group of Ala linked to the Boc moiety was also
clearly downfield-shifted from d = 5.91 to 5.98 ppm (Dd =
0.07 ppm, Fig. 7D) and 5.94 ppm (Dd = 0.03 ppm, Fig. 7E)
for (S)- and (R)-Ala anion, respectively. The above results in-
dicate that S-1 has a stronger interaction with the (S)-Ala
anion than with its (R)-enantiomer. This indicated that the in-
teraction between the host and guest also happened by multi-
ple hydrogen bondings. The results also illustrate that the
nature of the receptor, multiple hydrogen-bonding interactions,
and complementary chiral-center interactions maybe responsi-
ble for the enantiomeric recognition of the amino acid anion.19
According to Table 1, the interaction of S-1 with the (S)-
Ala and (S)-Phe anions is better than that with the (R)-Ala
and (R)-Phe anions, which is probably due to the (S)-amino
acid anions having a more complementary structure with re-
ceptors S-1. The receptors S-1 and R-1 all exhibit good chi-
ral recognition ability towards the enantiomers of the Ala
and Phe anions, which indicates that the preorganized struc-
ture of the chiral center of the binaphthyl unit plays impor-
tant roles in the enantioselective recognition process.
Conclusion
In summary, four chiral fluorescent receptors S-1, R-1, S-
5, and R-5 were synthesized, and their enantioselective rec-
ognition was studied by fluorescence titration and H NMR
1H NMR study
1
1H NMR experiments were undertaken to assess the chi-
ral-recognition properties between receptor S-1 and chiral
anionic guest because NMR spectroscopy can provide struc-
tural and dynamic information directly.18 1H NMR chiral-
recognition studies were carried out with a 400 MHz NMR
spectrometer using receptor S-1 in CDCl3 as chiral solvating
agent at room temperature. The spectra of receptor S-1 and
its complexes with equimolar amounts of racemic Ala
anions are shown in Fig. 7. When treated with equimolar
amounts of receptor S-1, the signal of the CH proton of the
racemic Ala anion cleaved into a more complicated signal
pattern (Fig. 7C) with a downfield shift. The interaction of
receptor S-1 with (S)-enantiomer showed that the CH proton
has a larger downfield shift (from d = 3.85 to 4.27 ppm, Dd =
spectroscopy. Receptors S-1 and R-1 exhibit different chiral-
recognition abilities towards some enantiomers of chiral ma-
terials and form 1:1 complexes with the guest molecules. It
is clear that the nature of the receptor, good structural preor-
ganization, multiple hydrogen-bonding interactions, and
complementary chiral-center interactions may be responsible
for the enantiomeric recognition of anionic guests.19 Recep-
tors S-1and R-1 are promising in their use as fluorescence
sensors for amino acid anions. The remarkably different flu-
orescent responses that result from complexation reveal that
S-1 and R-1 could be used as fluorescent chemosensors for
the N-Boc-protected alanine anion or N-Boc-protected phe-
nylalanine anion in the future.
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372
Can. J. Chem. Vol. 88, 2010
1
Fig. 7. The H NMR spectra of S-1 and its guest complexes at 25 8C ([S-1] = [guest] = 4.0 ꢀ 10–3 mol L–1) in CDCl3 at 400 MHz.
(A) Racemic Ala anion; (B) receptor S-1; (C) receptor S-1 + racemic Ala anion; (D) receptor S-1 + (S)-Ala anion; (E) receptor S-1 + (R)-
Ala anion.
kinElmer Model 341 polarimeter. Fluorescence spectra were
obtained with a F-7000 FL Spectrophotometer. Elemental
analyses were performed by the Vario Elemental CHSN-O
microanalyzer. The anions were used as their tetrabutylam-
monium salts. The N-protected (by the tert-butyloxycarbonyl
functionality) amino acid derivatives were synthesized ac-
cording to a literature method.20
Experimental section
General
The reagents used were of commercial origin and were
employed without further purification. Purifications by col-
umn chromatography were carried out over silica gel (230–
400 mesh). The IR spectra were performed on a Nicolet 670
1
FTIR spectrophotometer. H and 13C NMR spectra were re-
The synthesis of compound 3
Under N2, excess ethylenediamine (0.60 g, 10 mmol) in
10 mL CH3OH was added dropwise into a solution (20 mL)
corded on a Bruker AV-400 spectrometer. Mass spectra
were determined by ESI recorded on a Esquire 3000 LC–
MS mass instrument. Optical rotations were taken on a Per-
Published by NRC Research Press

Xu et al.
373
of (S)-N-Boc-protected alanine methyl ester (2) (0.41g,
2 mmol) in CHCl3/CH3OH (1:10, v/v) in an ice-bath. After
the addition, the mixture was stirred at room temperature
for 48 h. The solvent was evaporated, and the residual ethyl-
enediamine was removed under reduced pressure. Then,
CHCl3 (30 mL) was added and washed with H2O (3 ꢀ
30 mL); the organic layer was separated and dried over
Na2SO4. After filtration, the solvent was removed under re-
duced pressure to give 3 as colorless ropy oil in 86% yield
(0.40 g). ½aꢁD þ 21:84 (c = 0.05, CHCl3). H NMR (CDCl3)
d (ppm): 7.01 (s, 1 H, CONH), 5.47 (s, 1 H, NHBoc), 4.18
(CH), 3.31 (t, J =6.4 Hz, 2H, CH2), 2.82 (t, J = 6.4 Hz, 2H,
CH2), 1.72 (s, 2 H, NH2), 1.44 (s, 9 H, CH3), 1.35 (t, J =
6.8 Hz, 3 H, CH3). 13C NMR (CDCl3) d (ppm): 172.8,
155.2, 77.8, 54.1, 41.2, 40.3, 28.8, 27.9. ESI-MS m/z (%):
232 (100) [M + 1]+. C10H21N3O3 calcd.: C 51.93, H 9.15, N
18.17; found: C 51.66, H 9.22, N 18.04.
(CDCl3) d (ppm): 172.39, 152.53, 152.51, 134.32, 133.76,
132.91, 132.69, 131.29, 130.69, 130.54, 130.12, 129.94,
128.34, 127.38, 126.95, 126.07, 125.86, 125.59, 125.22,
124.96, 71.02, 57.31, 57.09, 39.89, 24.95, 14.44, 14.14.
ESI-MS m/z (%): 795 (100) [M + Na]+. C42H56N6O8 calcd.:
C 65.26, H 7.30, N 10.87; found (S-1): C 65.11, H 7.21, N
10.99; found (R-1): C 65.07, H 7.19, N 11.02.
S-5 and R-5
20
20
1
Yield (S-5): 79.6%; ½aꢁD ¼ ꢂ68:32 (c = 0.05, CHCl3). IR
(film, cm–1) y: 3402, 3092, 2969, 1679, 1529, 1268, 1234,
1
752. H NMR (CDCl3) d (ppm): 7.89 (s, 2H, CONH), 7.87
(d, J = 8.0 Hz, 2H, Ar–H), 7.79 (d, J = 9.6 Hz, 2H, Ar–H),
7.64 (d, J = 8.1 Hz, 2H, Ar–H), 7.22 (d, J = 7.6 Hz, 2H, Ar–
H), 7.19 (d, J = 7.2 Hz, 2H, Ar–H), 7.17–7.13 (t, J = 4.8 Hz,
2H, Ar–H), 6.55 (s, 2H, OH), 4.12 (d, J = 8.0 Hz, 4H, Ar–
CH2), 3.88 (s, 4H, CH2), 3.03–2.95 (m, 4H, CH2), 2.79–2.70
(m, 4H, CH2), 2.38 (s, 2H, NH), 1.44 (s, 18H, CH3). 13C
NMR (CDCl3) d (ppm): 174.03, 153.59, 153.31, 134.99,
133.96, 133.44, 133.17, 132.54, 131.06, 130.86, 130.58,
129.91, 128.71, 127.53, 126.62, 126.01, 125.93, 125.85,
125.73, 124.58, 74.09, 58.39, 58.49, 39.89, 24.92. ESI-MS
m/z (%): 767 (100) [M + Na]+. C40H52N6O8 calcd.: C 64.50,
H 7.04, N 11.28; found (S-5): C 64.29, H 7.09, N 11.19;
found (R-5): C 64.33, H 7.11, N 11.15.
The preparation of tert-butyl-2-(2-aminoethylamino)-2-
oxoethylcarbamate
Tert-butyl-2-(2-aminoethylamino)-2-oxoethylcarbamate
was prepared by the same method as that of compound 3 by
starting with N-Boc-protected glycine methyl ester, and it
1
gave 95% yield. H NMR (CDCl3) d (ppm): 7.11 (s, 1H,
CONH), 5.57 (s, 1H, NHBoc), 3.74 (s, 2H, CH2), 3.39 (t,
J = 6.4 Hz, 2H, CH2), 2.86 (t, J = 8.0 Hz, 2H, CH2), 1.74
(s, 2 H, NH2), 1.44 (s, 9 H, CH3). 13C NMR (CDCl3) d
(ppm): 173.3, 155.9, 78.1, 55.7, 41.9, 40.7, 28.9. ESI-MS:
m/z (%) = 218 (100) [M + 1]+. C9H19N3O3 calcd.: C 49.75,
H 8.81, N 19.34; found: C 49.57, H 8.89, N 19.22.
Preparation of samples for fluorescence measurement
All solutions were prepared using volumetric syringes,
pipettes, and volumetric flasks. The tetrabutylammonium
salts were prepared by adding 1 equiv. of tetrabutylammo-
nium hydroxide in methanol to a solution of the correspond-
ing carboxylic acid in methanol, and stock solutions of the
salts were prepared in CHCl3. The resulting syrup was dried
under high vacuum for 24 h, analyzed by NMR spectro-
scopy, and stored in a desiccator. Compounds R-1 and S-1
were prepared as stock solutions in CHCl3. The test solu-
tions were prepared by adding different volumes of anion
solution to a series of test tubes, and then the same amount
of stock solution of the host compound was added to each of
the test tubes and diluted to 3.0 mL with CHCl3. After being
shaken for several minutes, the test solutions were analyzed
immediately.
General procedure for the synthesis of compounds R-1,
S-1, R-5, and S-5
A mixture of the (R) or (S)-binaphthyl dialdehyde (0.34 g,
1 mmol) and compound 3 or tert-butyl-2-(2-aminoethyla-
mino)-2-oxoethylcarbamate (2.2 mmol) in CH3OH (30 mL)
was stirred for 48 h under N2 at room temperature until
TLC showed the disappearance of the starting material.
NaBH4 (0.19 g, 5 mmol) was then added to the mixture in
three portions over 3 h, after which it was stirred under N2
for another 6 h at 50 8C. The mixture was poured into
30 mL of 10% NaHCO3 after removing the solvent under
reduced pressure, and extracted three times with CHCl3.
The organic layers were combined and dried over anhydrous
Na2SO4. After filtration, the solvent was evaporated under
reduced pressur,e and the residue was purified by column
chromatography on silica gel [eluent: CHCl3/CH3CH2OH,
50:1 (v/v)]. The pure product was obtained as a pale yellow
solid.
Job Plots
Stock solutions of host S-1 and the (S)- and (R)-Ala tetra-
butylammonium salts in CHCl3 system (the total concentra-
tion of the host and guest is 1.0 ꢀ 10–6 mol L–1) were
freshly prepared. The receptor and Ala solutions were added
to the test tubes in ratios of 9:1, 8:2 to 0:10, respectively.
After being shaken for several minutes, the working solution
could be measured immediately.
S-1 and R-1
20
Yield (S-1): 76.8%; ½aꢁD ꢂ 34:72 (c = 0.05, CHCl3).
Acknowledgments
20
1
Yield (R-1): 79.3%; ½aꢁ þ 117:18 (c = 0.05, CHCl3). H
NMR (CDCl3) d (ppm):D7.87 (s, 2H, CONH), 7.83 (d, J =
8.0 Hz, 2H, Ar–H), 7.76 (d, J = 9.6 Hz, 2H, Ar–H), 7.61
(d, J = 8.1 Hz, 2H, Ar–H), 7.28 (d, J = 7.6 Hz, 2 H, Ar–H),
7.19 (d, J = 7.2 Hz, 2H, Ar–H), 7.13–7.16 (t, J = 4.8 Hz,
2H, Ar–H), 6.52 (s, 2H, OH), 4.76–4.68 (m, 2H, CHCH2),
4.10 (d, J = 8.0 Hz, 4H, Ar–CH2), 3.00–2.91 (m, 4H, CH2),
2.73–2.64 (m, 4H, CH2), 2.36 (s, 2H, NH), 1.42 (s, 18H,
CH3), 1.28 (s, 3H, CH3), 1.22 (s, 3H, CH3). 13C NMR
We thank the National Natural Science Foundation of
China (Grant No. 20872027/B0206) and the Education De-
partment of Henan Province of China (2010B150004) for fi-
nancial support.
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