Synthesis and enantioselective transport studies of optically active lipophilic proton-ionizable crown ethers containing a diarylphosphinic acid unit

Article abstract of DOI:10.1016/j.tetasy.2015.04.015

The synthesis of new enantiopure lipophilic crown ethers (S,S)-2, (S,S)-3, (R,R)-3, and (R,R)-4 containing a diarylphosphinic acid unit has been accomplished. The transport ability of these ligands has been studied in an aqueous source phase/lipophilic or

Full text of DOI:10.1016/j.tetasy.2015.04.015

Tetrahedron: Asymmetry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis and enantioselective transport studies of optically active
lipophilic proton-ionizable crown ethers containing a
diarylphosphinic acid unit
Tamás Szabó a, Edit Hirsch a, Tünde Tóth a, Judit Müller b, Eszter Riethmüller b, György T. Balogh b,
Péter Huszthy a,
⇑
a Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, H-1521 Budapest, Hungary
b Compound Profiling Laboratory, Chemical Works of Gedeon Richter Plc., PO Box 27, H-1475 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of new enantiopure lipophilic crown ethers (S,S)-2, (S,S)-3, (R,R)-3, and (R,R)-4 containing a
diarylphosphinic acid unit has been accomplished. The transport ability of these ligands has been studied
in an aqueous source phase/lipophilic organic bulk liquid membrane/aqueous receiving phase system
controlled by the pH of the media. The enantioselective transport of chiral amines has also been
investigated.
Received 2 April 2015
Accepted 30 April 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
It is noteworthy that proton-ionizable crown ethers are not only
used in the transport across the above mentioned membrane
Among carrier molecules, ionophores operating by a ‘switching
mechanism’ form a very important group.1 These ionophores can
have a high ion-binding ability at the source phase/lipophilic mem-
brane interface and a low ion binding ability at the lipophilic mem-
brane/receiving phase interface in an aqueous source
phase/lipophil membrane/aqueous receiving phase bulk liquid
membrane system, thus these carriers can perform active transport
of ions.1,2
Proton-ionizable crown ethers belong to this group and these
macrocycles have attracted the attention of many researchers.
These crown ethers at higher pHs than their pKa values are mostly
ionized, which increases the cation–ionophore complex
stability.3–30
In the case of the active transport of amines across the above
mentioned membrane system, the pKa of the conjugated acid of
the counter anion of the protonated amine should be higher than
that of the carrier at the source phase/membrane interface, and
the receiving phase should be an aqueous solution of a stronger
acid than the proton-ionizable ionophore. In this case, the complex
formation of the protonated amine with the anion of the carrier is
favorable at the source phase/membrane interface, and at the
membrane/receiving interface the dissociation of the complex is
favoured.
system, but are also applied in solvent extraction,31–36 and ion
flotation.37–40
For the successful operation of the above mentioned transport
of cations such as metal ions or protonated amines, it is indispens-
able that the carrier has to be lipophilic enough to stay in the
lipophilic membrane, while a relatively low pKa is necessary for
it to form a stable association with the guest molecules. Keeping
these requirements in mind, we inserted a relatively acidic
diarylphosphinic acid unit and two long alkyl chains into the
macro ring of the crown ethers.2,28 The aromatic rings of these
crown ethers render a rigid conformation, which increases the
selectivity of the complexation of the macrocycles.2
Herein we report our new results of this work. Earlier we syn-
thesized lipophilic crown ethers (S,S)-1 and (R,R)-1 and studied
the transport of metal ions and protonated achiral amines of these
ligands.2 We also wanted to investigate the effect of the substitu-
tion of the aromatic ring on the transport ability. For this purpose,
the synthesis of new tert-butyl- and nitro-substituted macrocycles
(S,S)-2, (S,S)-3, (R,R)-3 and (R,R)-4 (see Fig. 1) was carried out. To
the best of our knowledge, only one paper41 has reported the enan-
tioselective transport of protonated chiral amines across an aque-
ous source phase/lipophilic membrane/aqueous receiving phase
bulk liquid system, but in that case it was a passive one, thus the
receiving phase had to be replaced by distilled water from time
to time.
⇑
Corresponding author. Tel.: +36 1 463 1071; fax: +36 1 463 3297.
E-mail address: huszthy@mail.bme.hu (P. Huszthy).
http://dx.doi.org/10.1016/j.tetasy.2015.04.015
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

2
T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
R1
R1
phosphate 6 in good overall yield. Phosphate 6 was ortho-lithiated
with lithium diisopropyl amide, which was followed by an
intramolecular rearrangement to give dihydroxy phosphinate 5
(see Scheme 1).
O
O
R2
R2
P
P
Macrocyclization was carried out by the reaction of the
reported2 ditosylates (S,S)-7 and (R,R)-7 and ethyl phosphinate 5
at 80 °C in DMF using K2CO3 as a base (see Scheme 2).
Macrocycles (S,S)-8, (R,R)-8, and their reported2 analogues (S,S)-
9 and (R,R)-9 were nitrated with an HNO3/H2SO4 mixture. In the
case of the reported crown ethers (S,S)-9 and (R,R)-9, the nitro
groups were introduced selectively into positions ‘2’ and ‘23’ of
the aromatic rings; in the case of the tert-butyl-substituted ones
(S,S)-8 and (R,R)-8, because of the occupation of the above men-
tioned positions, the nitro groups were introduced into positions
‘4’ and ‘21’ (see Scheme 3).
O
O
OH
O
O
O
O
OH
O
O
∗
∗
∗
∗
H21C10
C10H21
H21C10
C10H21
O
O
(S,S)-2: R1 = tBu, R2 = H
1
(S,S)-
(S,S)-3: R1 = tBu, R2 = NO2
(R,R)-3: R1 =t Bu, R2 = NO2
(R,R)-1
(R,R)- : R1 = NO2, R2= H
4
Figure 1. Reported and newly synthesized enantiopure lipophilic proton-ionizable
crown ethers.
Ethyl phosphinates (S,S)-8, (S,S)-10, and (R,R)-10 were hydro-
lyzed by the reported method2 using aqueous Me4NOH as a base
in propanol (see Scheme 4).
In the case of macrocycles (S,S)-11 and (R,R)-11 with nitro
groups at positions ‘2’ and ‘23’, that is, para-positions to the ether
Herein we report an active enantioselective transport of proto-
nated phenylethyl amine and phenylglycinol controlled by the pH
of the media. We should emphasize that in our case the degree of
enantioselectivity was modest, but the method works, and its
effectiveness depends on the experimental conditions to a great
extent, thus we hope that further efforts could enhance enan-
tiomeric discrimination.
R
R
R1
R1
O
O
2. Results and discussion
2.1. Synthesis
P
R2
P
R2
HNO3/H2SO4
CH2Cl2
O
O
OEt
O
O
O
O
OEt
O
O
∗
∗
∗
∗
H21C10
C10H21
H21C10
C10H21
tert-Butyl-substituted crown ethers were prepared via macro-
cyclization of the reported tetraethylene glycol ditosylate2 (S,S)-7
and (R,R)-7, and a new dihydroxy ethyl phosphinate 5, which
was synthesized analogously to the reported procedure used to
obtain a similar phosphinate.42 In our case, P(O)Cl3 was reacted
with 2 equiv of 4-tert-butyl phenol in the presence of a Lewis acid.
The chlorophosphate intermediate was transformed to ethyl
O
O
(S,S)-8: R = tBu
(S,S)- : R1 = tBu, R2 = NO2 (71%)
10
(R,R)- : R1 = tBu, R2 = NO2 (33%)
8
(R,R)- : R = t Bu
10
11
(S,S)-9: R = H
(R,R)-9: R = H
(S,S)- : R1 = NO2, R2 = H (48%)
(R,R)- : R1 = NO2, R2 = H (58%)
11
Scheme 3. Nitration of crown ethers containing an ethyl diarylphosphinate unit.
tBu
O
O
1. AlCl3, heat
Cl
P
Cl
+
2
tBu
O
P
O
tBu
2. EtOH, Et3N
Cl
OEt
6
OH
(47%)
tBu
tBu
BuLi, iPr2NH
THF, -78°C
O
P
OH
OEt OH
(63%)
5
Scheme 1. Synthesis of the new tert-butyl-substituted dihydroxy phosphinate 5.
t Bu
tBu
O
P
TsO
O
O
O
OTs
K2CO3, DMF
80°C
O
O
O
O
OEt
5
+
∗
∗
H21C10
H21C10
∗
∗
H21C10
C10H21
7
7
(S,S)- or (R,R)-
O
(S,S)-8 (43%)
(R,R)-8 (70%)
Scheme 2. Macrocyclization reaction.
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
3
(S,S)-8
was 4 h, because in longer reaction, the ee decreased, while at
shorter reaction times, the transported amount was too small.
Using other acids in the source phase led to the transported
amount being effected, while the ee did not improve (see
Table 2). The transport rate of PEA was smaller in the case of a
stronger acid than acetic acid.
(S,S)-2: R = H (85%)
(S,S)- : R = NO2 (63%)
(R,R)-3: R =NO2 (57%)
1. Me4NOH/H2O/PrOH (heat)
2. H2O/HCl
10
(S,S)-
(R,R)-
3
10
Scheme 4. Basic hydrolysis of crown ethers containing an ethyl diarylphosphinate
unit.
Considering these results, acetic acid was chosen as the acid in
the source phase and the transport time was set to 4 h. Under these
conditions, the temperature dependence of the transport was
examined using CH2Cl2 as a bulk liquid membrane. From our
results, it can be seen that the temperature effects the enantiose-
lectivity of the transport to a great extent. Increasing the tempera-
ture led to an increase in the rate of the transport as well (see
Table 3). We chose 18 °C as the temperature for further
experiments.
At 18 °C, the influence of the lipophilic membrane was studied.
CH2Cl2 seemed to be the best membrane with regard to both the ee
and the amount of the transported amine into the receiving phase
in 4 h (see Table 4).
oxygens on the aromatic rings, basic hydrolysis caused decomposi-
tion. Macrocycle (R,R)-11 was hydrolyzed successfully by using a
mixture of dioxane–aqueous HCl solution (see Scheme 5).
dioxane/aqueous HCl
(R,R)-11
(R,R)-4 (48%)
(heat)
Scheme 5. Acidic hydrolysis of crown ether (R,R)-11 containing an ethyl
diarylphosphinate unit.
2.2. Transport studies
The concentrations of the starting source and receiving phases
effected the transport as well, but the first used concentrations
seemed to be the optimal ones (see Table 5).
The effect of the substituents of the aromatic rings of the
macrocycles was also studied. Using the optimal circumstances
(4 h, 18 °C, CH2Cl2 membrane, 1 M aqueous PEAÁAcOH solution
source phase, 2% aqueous HCl solution receiving phase), the trans-
port of PEA was investigated (see Table 6). The transports were
much faster in the cases of the substituted ligands, but the enan-
tioselectivity decreased.
Transport studies were carried out in a bulk liquid membrane
cell as reported earlier43 (see Fig. 2). The errors of the amounts of
transported amines were smaller than 2%, and the errors of the
ee values were smaller than 0.5% (from three independent mea-
surements). The transport of benzyl amine was studied using sub-
stituted macrocycles as carriers, and the results were compared to
those of the reported one (S,S)-1.2 The source phase was the aque-
ous solution of the acetate of the amine, the membrane was CH2Cl2
and the receiving phase was an aqueous HCl solution. The results
show that tert-butyl substituents, which increase the pKa of the
ligand, accelerate the transport, and the nitro groups, which lower
the pKa of the ligand, decelerate the transport of benzyl amine (see
Table 1).
The transport of another amine, phenylglycinol was also stud-
ied. The transport of this amine was much slower than that of
The conditions for the enantioselective transport of PEA (pheny-
lethyl amine) was investigated. The effect of the time, membrane,
and temperature, the concentration of the source and receiving
phase, and the effect of the acid in the source phase were
examined.
In these experiments the source phase was 1 M PEAÁAcOH, the
receiving phase was 2% aqueous HCl solution, and the membrane
was 1 mM (S,S)-1 solution in CH2Cl2, unless otherwise stated.
Experiments at rt showed that the optimal time of the transport
Table 2
Effect of time and the acid in the source phase for the transport of phenylethylamine
Source phase
Time (h)
Amount of transported
amine (%)
ee (%)
PEAÁAcOH
PEAÁAcOH
PEAÁAcOH
PEAÁHCOOH
PEAÁHF
4
8
24
16
20
13
30
60
13
14
15
12
0
10
9
Table 3
Effect of temperature to the transport of phenylethylamine
Temperature (°C)
Amount of transported
amine (%)
ee (%)
0
10
18
30
6
14
14
37
2
10
13
0
Figure 2. Bulk liquid membrane cell; (a) source phase, (b) receiving phase, (c)
membrane, (d) magnetic stirrer (100 rpm).
Table 4
Effect of the membrane on the transport of phenylethylamine
Membrane
Amount of transported
amine (%)
ee (%)
Table 1
Transport of benzyl amine
CH2Cl2
CHCl3
CCl4
14
24
5
13
0
2
Ligand
Amount of transported
amine (%) after 24 h
(S,S)-1
(S,S)-2
(S,S)-3
(R,R)-4
46
51
41
37
Ph-Br
1,2-Dichlorobenzene
6
2
1
7
4
14
4
a,a
,a
-Trifluorotoluene
Tetrachloroethylene
4
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

4
T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
rotations of both enantiomers of menthol. 1H NMR spectra
(500 MHz, reference: TMS) were obtained on a Bruker DRX-500
Avance spectrometer. 13C NMR spectra were taken either on a
Bruker DRX-500 Avance spectrometer (125.8 MHz, reference:
TMS) or on a Bruker 300 Avance spectrometer (75.5 MHz, refer-
ence: TMS) and is indicated in each individual case. 31P NMR spec-
tra (121.5 MHz, reference: H3PO4) were recorded on a Bruker 300
Avance spectrometer. HPLC-DAD-MS/MS measurements were per-
formed on an Agilent 1200 HPLC system (G1379B degasser,
G1312B binary gradient pump, G1367C autosampler, G1316B col-
umn thermostat and G1315C diode array detector) coupled with
an Agilent 6410 triple quadrupole mass spectrometer equipped
with an ESI ion source (Agilent Technologies, Waldbronn,
Germany). Masshunter B.03.01 software was used for data acquisi-
tion and qualitative analyses. Chiral HPLC measurements were car-
Table 5
Effect of the concentrations on the transport of phenylethylamine
Source
phase (M)
Receiving phase
Amount of transported
amine (%)
ee (%)
1
1
0.5
0.1
0.5 equiv HCl (0.3% HCl)
1.6 equiv HCl (2% HCl)
3.2 equiv HCl(2% HCl)
16 equiv HCl (2% HCl)
16
14
15
25
7
13
2
4
Table 6
Effect on the substitution of the ligand
Ligand
Amount of transported
amine (%)
ee (%)
(S,S)-1
(S,S)-2
(S,S)-3
(R,R)-4
14
31
30
29
13
4
2
ried out on
a Phenomenex, Lux Cellulose-2 column (5 lm,
250 Â 6 mm). Chiral GC experiments were performed using
Supelco b-DEX™ 120 column. Elemental analyses were performed
in the Microanalytical Laboratory of the Department of Organic
Chemistry, Institute of Chemistry, L. Eötvös University, Budapest,
Hungary. Starting materials were purchased from Sigma–Aldrich
Corporation unless otherwise noted. Silica gel 60 F254 (Merck)
plates were used for TLC. Silica gel 60 (70–230 mesh, Merck) were
used for column chromatography. Ratios of solvents for the eluents
are given in volumes (mL/mL). Solvents were dried and purified
according to well-established44 methods. Evaporations were car-
ried out under reduced pressure unless otherwise stated.
4
Table 7
Transport of phenylglycinol
Ligand
Amount of transported
amine (%)
ee (%)
(S,S)-1
(S,S)-2
(S,S)-3
(R,R)-4
24
24
23
21
12
17
7
3
4.2. Synthesis
4.2.1. Bis(4-tert-butylphenyl)-ethylphosphate 6
PEA, and so the time of the transport was set to 24 h. The other cir-
cumstances were the same as the above mentioned optimal ones.
The transports also showed some enantioselectivity in this case
(see Table 7). The best enantioselectivity and the largest trans-
ported amount were obtained using ligand (S,S)-2 with tert-butyl
substituents. Nitro-substitution of the aromatic rings decreased
the enantioselectivity and the rate of the transport. In the case of
macrocycles with an (S,S)-configuration, (S)-PEA and (S)-phenyl-
glycinol were enriched in the receiving phase. Using crown ether
4 with an (R,R)-configuration resulted in the other enantiomer of
phenylglycinol (R) enriched in the receiving phase. This led to
the preference of homochiral complex formation in both cases
(PEA, phenylglycinol).
To
a
stirred mixture of phosphoryl chloride (10.00 g,
65.20 mmol) and finely powdered tert-butylphenol (20.57 g,
137.0 mmol), AlCl3 (0.3836 g, 2.870 mmol) was added. The reac-
tion temperature was raised to 70 °C and kept at this temperature
for one hour, and then raised to 150 °C and kept at this tempera-
ture until the evolution of HCl ceased. To remove HCl, the reaction
mixture was put under reduced pressure. Without further purifica-
tion,
a mixture of ethanol (18.2 mL, 311.7 mmol) and Et3N
(45.5 mL, 326.2 mmol) was added dropwise at À20 °C under Ar.
The reaction mixture was then stirred for 3 days. The volatile com-
ponents were removed. The residue was triturated with 1% (w/w)
aqueous HCl (100 mL) and then extracted with ether (3 Â 100 mL).
The combined organic phase was shaken with water (100 mL),
dried over MgSO4, filtered, and the solvent was removed. The crude
product was purified by chromatography on silica gel using ethyl
acetate–hexane (1:10) as an eluent to give 6 (11.89 g, 47%) as a col-
orless oil. Rf: 0.45 (silica gel TLC, ethyl acetate–hexane 1:4); IR
(neat): mmax 3071, 3032, 2922, 2910, 2852, 1594, 1579, 1471,
1448, 1360, 1277, 1236, 1134, 1095, 1025, 943, 817, 761, 710,
3. Conclusion
Enantiopure lipophilic proton-ionizable crown ethers (S,S)-1,
(S,S)-2, (S,S)-3, (R,R)-4 are suitable carriers for the enantioselective
active transport controlled by the pH of the media. According to
our results, chiral carriers form homochiral complexes more
favourably than heterochiral ones. The substitution of the aromatic
rings, the temperature, the quality of the lipophilic membrane, and
the acid in the source phase effect the rate and enantioselectivity of
the transport. In the future we would like to study the transport of
several selected biologically important amines, and also improve
the enantioselectivity by altering the structures of the carriers
and the experimental conditions.
554, 511 cmÀ1 1H NMR (500 MHz, CDCl3): d 1.34 (s, 18H, CH3),
;
1.41 (t, J = 7.5 Hz, 3H, CH3), 4.33–4.39 (m, 2H, OCH2), 7.18 (d,
J = 8 Hz, 4H, ArH), 7.37 (d, J = 9 Hz, 4H, ArH); 13C NMR (75 MHz,
CDCl3): d 16.26 (d, J = 6.75 Hz, CH3), 31.58 (CH3), 34.58 (C), 65.48
(d, J = 6 Hz, OCH2), 119.61 (d, J = 4.5 Hz, ArCH), 126.76 (ArCH),
148.26 (ArC), 148.51 (d, J = 6.75 Hz, ArC); 31P NMR (121.5 MHz,
CDCl3): d À11.23; Anal. Calcd for C22H31O4P: C, 67.67; H, 8.00.
Found: C, 67.64; H, 8.01.
4. Experimental
4.1. General
4.2.2. Ethyl[bis(5-tert-butyl-2-hydroxyphenyl)phosphinate] 5
To
a vigorously stirred solution of (iPr)2NH (12.95 mL,
92.40 mmol) in dry and pure THF (20 mL) at À78 °C, BuLi (2.5 M
solution in hexane, 36.93 mL, 92.40 mmol) was added dropwise
under argon. A solution of ester 6 (9.01 g, 23.1 mmol) in dry and
pure THF (20 mL) was then added dropwise to the lithium diiso-
propylamide solution, and this mixture was stirred for one hour
Infrared spectra were recorded on a Bruker Alpha-T FT-IR spec-
trometer. Optical rotations were taken on a Perkin–Elmer 241
polarimeter, which was calibrated by measuring the optical
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
5
at À78 °C and for an additional 4 h at room temperature. The reac-
tion mixture was slowly poured into a mixture of CH2Cl2 (90 mL),
satd aqueous NH4Cl solution (200 mL), and ice (50 g), and the
phases were shaken thoroughly. The phases were separated and
the aqueous phase was shaken with CH2Cl2 (4 Â 50 mL). The com-
bined organic phase was dried over MgSO4, filtered, and the sol-
vent was removed. The residue was filtered through a silica gel
pad using CH2Cl2 as a solvent. The solvent was removed and the
crude product was recrystallized from toluene to give 5 (5.68 g,
63%) as a white powder. Mp 120–122 °C; Rf: 0.64 (silica gel TLC,
ethyl acetate–hexane 1:4); IR (neat): mmax 3260 (broad), 3073,
2961, 2870, 1617, 1602, 1584, 1487, 1398, 1361, 1297, 1260,
1245, 1229, 1201, 1143, 1126, 1084, 1028, 970, 952, 824, 782,
0.53 g (70%). [
a
]
25 = À37.8 (c 1.00, CH2Cl2). Other physical and
D
spectroscopic data of (R,R)-8 concurred with those of (S,S)-8.
4.2.3. General procedure for nitration
To a vigorously stirred solution of the crown ether in CH2Cl2, a
mixture of H2SO4–HNO3 (2:1, V/V) (2.2 equiv HNO3) was added at
0 °C. The reaction mixture was stirred at room temperature until
TLC analysis showed the total consumption of the starting mate-
rial. Next, CH2Cl2 and water were added to the mixture, and the
phases were shaken thoroughly. The phases were separated and
the aqueous phase was extracted with CH2Cl2 (2Â). The combined
organic phase was dried over MgSO4, filtered, and the solvent was
removed. The crude products were purified by chromatography on
silica gel using ethyl acetate–hexane as an eluent.
749, 610, 576, 552, 498 cmÀ1 1H NMR (500 MHz, CDCl3): d 1.29
;
(s, 18H, CH3), 1.42 (t, J = 5 Hz, 3H, CH3), 4.14–4.20 (m, 2H, OCH2),
6.90–6.93 (m, 2H, ArH), 7.40–7.44 (m, 2H, ArH), 7.47–7.49 (m,
2H, ArH), 9.92 (s, 2H, OH); 13C NMR (125 MHz, CDCl3): d 16.58
(d, J = 6.3 Hz, CH3), 32.52 (CH3), 34.31 (C), 62.69 (d, J = 6.3 Hz,
OCH2), 110.53 (d, J = 137.5 Hz, ArC), 118.25 (d, J = 10 Hz, ArCH),
127.52 (d, J = 7.5 Hz, ArCH), 133.06 (d, J = 2.5 Hz, ArCH), 142.59
(d, J = 12.5 Hz, ArC), 160.23 (d, J = 6.3 Hz, ArC); 31P NMR
(121.5 MHz, CDCl3): d 45.24; Anal. Calcd for C22H31O4P: C, 67.67;
H, 8.00. Found: C, 67.68; H, 8.04.
4.2.3.1.
(7S,15S)-2,20-Di-tert-butyl-7,15-didecyl-22-ethoxy-4,
18-dinitro-6,7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q]
[1,4,7,10,13,16]pentaoxa-k5-phosphacyclooctadecin-22-one
(S,S)-10.
Macrocycle (S,S)-8 (0.35 g, 0.42 mmol), CH2Cl2
(4 mL). Reaction time: 1 day, yield: 0.16 g (42%) as a pale yellow
oil. Rf: 0.80 (silica gel TLC, ethyl acetate–hexane 1:2);
[
a
]
25 = À56.0 (c 1.03, CH2Cl2); IR (neat): mmax 2956, 2923, 2854,
D
1605, 1560, 1533, 1466, 1365, 1351, 1241, 1109, 1029, 987, 957,
877, 731, 552, 460 cmÀ1 1H NMR (300 MHz, CDCl3): d 0.89 (t,
;
J = 6 Hz, 6H, CH3), 1.14–1.46 (m, 57H, CH2, CH3), 3.29–3.79 (m,
12H, OCH2), 3.94–3.99 (m, 1H, OCH), 4.17–4.32 (m, 3H, OCH,
OCH2), 7.68–7.74 (m, 1H, ArH), 7.94–7.98 (m, 2H, ArH), 8.09–8.15
(m, 1H, ArH); 13C NMR (75.5 MHz, CDCl3): d 14.14 (CH3), 16.58
(d, J = 6 Hz, CH3), 22.71, 24.61, 25.40, 29.35, 29.65, 29.85, 30.97,
31.11, 31.22, 31.88, 31.95, 34.86, 34.96 (C, CH2, CH3), 62.33 (d,
J = 6.0 Hz, OCH2), 68.35, 69.48, 70.16, 70.35, 76.02, 77.97, 78.12,
78.47 (OCH, OCH2), 126.06 (d, J = 2.3 Hz, ArC), 126.77 (d,
J = 2.3 Hz, ArC), 127.16 (d, J = 134.3 Hz, ArC), 129.03 (d,
J = 135.75 Hz, ArC), 134.84 (d, J = 12.8 Hz, ArCH), 134.92 (d,
J = 6.8 Hz, ArCH), 143.34 (d, J = 12 Hz, ArCH), 143.93 (d, J = 12 Hz,
ArCH), 147.23 (d, J = 12 Hz, ArC), 147.59 (d, J = 12.8 Hz, ArC),
151.83 (d, J = 4.5 Hz, ArC), 151.93 (d, J = 4.5 Hz, ArC); 31P NMR
(121.5 MHz, CDCl3): d 26.21; MS: 919.6 (M+1)+, 941.6 (M+23)+;
Anal. Calcd for C50H83N2O11P: C, 65.33; H, 9.10; N, 3.05. Found: C,
65.18; H, 8.92; N, 3.09.
4.2.2.1.
7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,
16] (S,S)-8.
pentaoxa-k5-phosphacyclooctadecin-22-one
(7S,15S)-2,20-Di-tert-butyl-7,15-didecyl-22-ethoxy-6,
Tetraethylene glycol ditosylate (S,S)-72 (1.00 g, 1.28 mmol), ethyl
phosphinate 5 (0.50 g, 1.28 mmol), and finely powdered anhydrous
K2CO3 (2.00 g) were mixed with vigorous stirring in dry DMF
(30 mL) under argon. The temperature of the reaction mixture
was raised to 80 °C and kept stirring at this temperature until
TLC analysis showed the total consumption of the starting materi-
als (12 days). The solvent was removed at 40 °C. Water was added
to the residue and then extracted with CH2Cl2 (3 Â 50 mL). The
combined organic phase was dried over MgSO4, filtered, and the
solvent was removed. The crude product was purified by chro-
matography on silica gel using ethyl acetate–hexane (3:1) as an
eluent to give (S,S)-8 as a colorless oil (0.46 g, 43%). Rf: 0.35 (silica
gel TLC, ethyl acetate–hexane 1:2); [
(neat): max 2954, 2922, 2853, 1599, 1489, 1465, 1393, 1362, 1263,
a]
25 = +34.5 (c 1.04, CH2Cl2); IR
D
m
4.2.3.2.
(7R,15R)-2,20-Di-tert-butyl-7,15-didecyl-22-ethoxy-4,
1089, 1036, 949, 813, 669, 584, 544, 505 cmÀ1; 1H NMR (500 MHz,
CDCl3): d 0.88 (t, J = 5.0 Hz, 6H, CH3), 1.25–1.33 (m, 57H, CH2, CH3),
2.84–3.09 (m, 4H, OCH2), 3.24–3.31 (m, 5H, OCH, OCH2), 3.41–3.44
(m, 1H, OCH), 3.71–3.78 (m, 2H, OCH2), 3.92–4.19 (m, 4H, OCH2),
6.88–6.91 (m, 2H, ArH), 7.41–7.46 (m, 2H, ArH), 7.89–8.00 (m,
2H, ArH); 13C NMR (75.5 MHz, CDCl3): d 14.30 (CH3), 16.75 (d,
J = 6.8 Hz, CH3), 22.87, 25.38, 25.47, 29.51, 29.74, 29.77, 29.79,
29.92, 30.00, 31.74, 31.76, 32.01, 32.10, 32.69, 34.45 (C, CH2,
CH3), 60.48 (d, J = 6.0 Hz, OCH2), 70.30, 70.45, 70.65, 70.75, 72.23,
72.51 (OCH2), 79.80, 79.88 (OCH), 112.33 (d, J = 7.5 Hz, ArCH),
112.77 (d, J = 9.0 Hz, ArCH), 119.80 (d, J = 53.3 Hz, ArC), 121.66
(d, J = 61.5 Hz, ArC), 130.07 (ArCH), 130.11 (d, J = 3.0 Hz, ArCH),
130.21 (d, J = 1.5 Hz, ArCH), 142.90 (d, J = 11.3 Hz, ArC), 143.12
(d, J = 12.0 Hz, ArC), 158.36 (d, J = 3.0 Hz, ArC), 158.86 (d,
J = 5.3 Hz, ArC); 31P NMR (121.5 MHz, CDCl3): d 28.55; MS: 829.6
(M+1)+, 851.6 (M+23)+; Anal. Calcd for C50H85O7P: C, 72.43; H,
10.33. Found: C, 72.23; H, 10.10.
18-dinitro-6,7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q]
[1,4,7,10,13,16]pentaoxa-k5-phosphacyclooctadecin-22-one
(R,R)-10. Macrocycle (R,R)-8 (0.53 g, 0.64 mmol), CH2Cl2 (8 mL).
Reaction time: 1 day, yield: 0.19 g (33%). [a]
25 = +58.5 (c 0.98,
D
CH2Cl2). Other physical and spectroscopic data of (R,R)-10 con-
curred with those of (S,S)-10.
4.2.3.3. (7S,15S)-7,15-Didecyl-22-ethoxy-4,18-dinitro-6,7,9,10,
12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,16]pentaoxa-
k5-phosphacyclooctadecin-22-one (S,S)-11.
Macrocycle (S,S)-
92 (0.10 g, 0.12 mmol), CH2Cl2 (1 mL). Reaction time: 4 days, yield:
0.053 g (48%) as a yellow oil. Rf: 0.80 (silica gel TLC, ethyl acetate–
hexane 1:1); [
2923, 2853, 1603, 1582, 1517, 1468, 1339, 1278, 1227, 1144,
1105, 1071, 1029, 956, 900, 822, 752, 650, 558, 508 cmÀ1 1H
a]
25 = +59.0 (c 0.58, CH2Cl2); IR (neat): mmax 3082,
D
;
NMR (300 MHz, CDCl3): d 0.88 (t, J = 6.4 Hz, 6H, CH3), 1.23–1.40
(m, 39H, CH2, CH3), 2.74–2.80 (m, 4H, OCH2), 3.08–3.28 (m, 4H,
OCH2), 3.34–3.47 (m, 2H, OCH2), 3.88–4.07 (m, 3H, OCH, OCH2),
4.16–4.31 (m, 3H, OCH, OCH2), 7.07–7.14 (m, 2H, ArH), 8.31–8.38
(m, 2H, ArH), 8.77–8.81 (m, 1H, ArH), 8.99–9.05 (m, 1H, ArH);
13C NMR (75.5 MHz, CDCl3): d 14.31 (CH3), 16.69 (d, J = 6.2 Hz,
CH3), 22.88, 25.32, 25.37, 29.51, 29.67, 29.73, 29.77, 29.78, 29.79,
29.86, 29.93, 31.41, 31.95, 32.11 (CH2), 61.73 (d, J = 5.6 Hz,
OCH2), 70.39, 70.86, 71.15, 72.30, 72.70 (OCH2), 79.96, 80.37
4.2.2.2.
7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,
16] (R,R)-
pentaoxa-k5-phosphacyclooctadecin-22-one
(7R,15R)-2,20-Di-tert-butyl-7,15-didecyl-22-ethoxy-6,
8. Macrocycle (R,R)-8 was prepared from 5 (0.36 g, 0.91 mmol)
and (R,R)-72 (0.71 g, 0.91 mmol) in the same way as described
above for (S,S)-8. The reaction was completed in 12 days. Yield:
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

6
T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
(OCH), 113.04 (d, J = 7.5 Hz, ArCH), 113.29 (d, J = 8.1 Hz, ArCH),
120.44 (d, J = 39.7 Hz, ArC), 122.34 (d, J = 52.5 Hz, ArC), 129.20
(d, J = 1.5 Hz, ArCH), 129.55 (d, J = 1.8 Hz, ArCH), 129.87
(d, J = 5.9 Hz, ArCH), 131.80 (d, J = 8.6 Hz, ArCH), 141.04
(d, J = 14.2 Hz, ArC), 141.37 (d, J = 15.1 Hz, ArC), 165.11 (d,
J = 3.8 Hz, ArC), 166.05 (d, J = 5.4 Hz, ArC); 31P NMR (121.5 MHz,
CDCl3): d 19.81; MS: 807.4 (M+1)+; Anal. Calcd for C42H67N2O11P:
C, 62.51; H, 8.37; N, 3.47. Found: C, 62.32; H, 8.39; N, 3.23.
(121.5 MHz, CDCl3): d 23.50; MS: 891.5 (M+1)+, 913.5 (M+23)+;
Anal. Calcd for C48H79N2O11P: C, 64.70; H, 8.94; N, 3.14. Found:
C, 64.76; H, 8.80; N, 3.06.
4.2.3.7. (7R,15R)-2,20-Di-tert-butyl-7,15-didecyl-22-hidroxy-4,
18-dinitro-6,7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q]
[1,4,7,10,13,16]pentaoxa-k5-phosphacyclooctadecin-22-one
(R,R)-3. Macrocycle (R,R)-3 was prepared from (R,R)-10 (0.13 g,
0.15 mmol) in the same way as described above for (S,S)-2. The
reaction was completed in 2 days. Yield: 0.076 g (57%).
4.2.3.4. (7R,15R)-7,15-Didecyl-22-ethoxy-4,18-dinitro-6,7,9,10,
12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,16]pentaoxa-
[
a
]
25 = À143.2 (c 1.00, CH2Cl2). Other physical and spectroscopic
D
k5-phosphacyclooctadecin-22-one (R,R)-11.
Macrocycle
data of (R,R)-3 concurred with those of (S,S)-3.
(R,R)-92 (0.48 g, 0.67 mmol), CH2Cl2 (5 mL). Reaction time: 1 day,
yield: 0.31 g (58%). [
a]
25 = À61.4 (c 0.58, CH2Cl2). Other physical
D
4.2.3.8. (7R,15R)-7,15-Didecyl-22-hydroxy-4,18-dinitro-6,7,9,10,
12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,16]pen-
and spectroscopic data of (R,R)-11 concurred with those of (S,S)-11.
taoxa-k5-phosphacyclooctadecin-22-one (R,R)-4.
To a stir-
4.2.3.5. (7S,15S)-2,20-Di-tert-butyl-7,15-didecyl-22-hydroxy-6,7,
9,10,12,13,15,16-octahydro-22H-dibenzo[n,q][1,4,7,10,13,16]
red solution of ethyl phosphinate (R,R)-11 (0.083 g, 0.104 mmol)
in dioxane (5 mL) aqueous HCl solution (10% w/w, 5 mL) was
added at rt. The mixture was heated at 80 °C with stirring until
TLC analysis showed the total consumption of the starting crown
ether (20 days). The solvent was then removed at 40 °C. The resi-
due was dissolved in a mixture of water (15 mL) and CH2Cl2
(10 mL). The phases were separated and the aqueous one was sha-
ken with CH2Cl2 (2 Â 10 mL). The combined organic phase was
shaken with water (20 mL), dried over MgSO4, filtered, and the sol-
vent was removed. The crude product was purified by PLC using
methanol–CH2Cl2 (1:15) as an eluent to give (R,R)-10 (0.039 g,
48%) as a yellow oil. Rf: 0.45 (silica gel TLC, methanol–CH2Cl2
pentaoxa-k5-phosphacyclooctadecin-22-one (S,S)-2.
To a vig-
orously stirred solution of enantiopure ethyl phosphinate (S,S)-8
(0.35 g, 0.42 mmol) in propanol (3 mL), 25% aqueous Me4NOH
(1.55 mL, 4.21 mmol) was added at rt. The reaction mixture was
heated at reflux temperature with stirring until TLC analysis
showed the total consumption of the starting (S,S)-8 (14 days).
Propanol was then removed at 40 °C. Water (40 mL) and CH2Cl2
(20 mL) were added to the residue and the pH of the mixture
was adjusted to 1 with 10% aqueous HCl solution (4 mL). The
phases were separated and the aqueous phase was extracted with
CH2Cl2 (3 Â 15 mL). The combined organic phase was dried over
MgSO4, filtered, and the solvent was removed. The residue was
purified by PLC using ethyl acetate–hexane–acetic acid (10:10:1)
as an eluent to give (S,S)-2 (0.29 g, 85%) as a colorless oil. Rf: 0.54
(silica gel TLC, ethyl acetate–hexane–acetic acid 10:10:1);
1:15); [
a
]
25 = À209.0 (c 1.00, CH2Cl2); IR (neat): mmax 3082, 2922,
D
2853, 1692, 1600, 1581, 1510, 1467, 1336, 1270, 1134, 1087,
1066, 1039, 897, 818, 752, 650, 560, 505 cmÀ1
;
1H NMR
(300 MHz, CDCl3+CD3OD): d 0.78 (t, J = 5.8 Hz, 6H, CH3), 1.12–
1.28 (m, 36H, CH2), 2.73–2.83 (m, 4H, OCH2), 3.20–3.34 (m, 6H,
OCH2), 3.78–4.01 (m, 4H, OCH, OCH2) 6.76–6.81 (m, 2H, ArH),
7.96–7.98 (m, 2H, ArH), 8.45–8.50 (m, 2H, ArH); 13C NMR
(75.5 MHz, CDCl3+CD3OD): d 14.02 (CH3), 22.66, 25.31, 29.31,
29.56, 29.67, 29.58, 29.66, 31.14, 31.90 (CH2), 69.96, 70.40, 71.42,
79.93 (OCH, OCH2), 112.17 (d, J = 6.9 Hz, ArCH), 117.01 (d,
J = 1.3 Hz, ArC), 127.39 (d, J = 1.3 Hz, ArCH), 129.78 (d, J = 6.0 Hz,
ArCH), 140.65 (d, J = 2.4 Hz, ArC), 164.79 (d, J = 0.8 Hz, ArC); 31P
NMR (121.5 MHz, CDCl3+CD3OD): d 20.77; MS: 779.5 (M+1)+;
Anal. Calcd for C40H63N2O11P: C, 61.68; H, 8.15; N, 3.60. Found:
C, 61.51; H, 8.32; N, 3.46.
[a]
25 = +48.7 (c 0.94, CH2Cl2); IR (neat): mmax 3648, 2953, 2923,
D
2854, 1918, 1718, 1700, 1685, 1598, 1489, 1457, 1361, 1091,
1030, 809, 588, 527, 505, 459 cmÀ1 1H NMR (300 MHz, CDCl3): d
;
0.89 (t, J = 6 Hz, 6H, CH3), 1.22–1.56 (m, 54H, CH2, CH3), 3.49–
3.55 (m, 2H, OCH2), 3.66–3.76 (m, 8H, OCH2), 3.92–4.01 (m, 4H,
OCH, OCH2) 6.71–6.76 (m, 2H, ArH), 7.31–7.33 (m, 2H, ArH),
7.62–7.76 (m, 2H, ArH); 13C NMR (75.5 MHz, CD3OD): d 13.10
(CH3), 22.37, 25.35, 29.11, 29.34, 29.36, 29.38, 30.01, 30.02,
30.56, 31.70, 33.71 (C, CH2, CH3), 68.22, 69.38, 70.67, 78.96 (OCH,
OCH2), 112.57 (d, J = 2.5 Hz, ArCH), 127.54 (d, J = 132.6 Hz, ArC),
128.01 (d, J = 1.1 Hz, ArCH), 130.41 (d, J = 7.8 Hz, ArCH), 143.19
(d, J = 10.6 Hz, ArC), 157.73 (d, J = 2.3 Hz, ArC); 31P NMR
(121.5 MHz, CD3OD): d 18.00; MS: 801.6 (M+1)+, 823.5 (M+23)+;
Anal. Calcd for C48H81O7P: C, 71.96; H, 10.19. Found: C, 71.86; H,
10.14.
4.3. Transport studies
The source phases were prepared using commercial amines and
the appropriate acid. The protonated amines were prepared as fol-
lows: the free amines were added to one equivalent of acid, and the
salts were dissolved in distilled water (1 M). The volume of the
source phases was 2 mL in all experiments. The receiving phase
was 6 mL of 2% aqueous HCl solution. The lipophilic membrane
was 12 mL of crown ether solution (1 mM) in CH2Cl2, or in another
indicated solvent. The time of transport was indicated in each
experiment. In cases where these conditions were modified, it is
indicated in the text. The ee values of the transported chiral amines
were determined by chiral GC or by chiral HPLC.
4.2.3.6. (7S,15S)-2,20-Di-tert-butyl-7,15-didecyl-22-hidroxy-4,
18-dinitro-6,7,9,10,12,13,15,16-octahydro-22H-dibenzo[n,q]
[1,4,7,10,13,16]pentaoxa-k5-phosphacyclooctadecin-22-one
(S,S)-3. Macrocycle (S,S)-3 was prepared from (S,S)-10 (0.21 g,
0.23 mmol) in the same way as described above for (S,S)-2. The
reaction was completed in 2 days. Yield: 0.13 g (63%) as a pale yel-
low oil. Rf: 0.76 (silica gel TLC, ethyl acetate–hexane–acetic acid
10:10:1); [
2923, 2854, 1605, 1560, 1532, 1465, 1364, 1351, 1236, 1109,
963, 878, 736, 721, 555, 497, 453 cmÀ1 1H NMR (500 MHz,
a]
25 = +98.9 (c 1.00, CH2Cl2); IR (neat): mmax 2955,
D
;
Acknowledgements
CDCl3): d 0.89 (t, J = 5 Hz, 6H, CH3), 1.26–1.38 (m, 54H, CH2, CH3),
3.63–3.75 (m, 10H, OCH2), 4.04–4.06 (m, 2H, OCH2), 4.29–4.33
(m, 2H, OCH), 7.84–7.97 (m, 4H, ArH); 13C NMR (75.5 MHz,
CDCl3): d 10.35, 14.33, 22.90, 25.67, 26.11, 29.54, 29.76, 29.81,
29.95, 30.54, 31.12, 32.13, 35.08 (C, CH2, CH3), 64.91, 68.96,
70.37 (OCH2), 78.32 (OCH), 125.94 (d, J = 1.5 Hz, ArCH), 147.86
(d, J = 12.8 Hz, ArCH), 151.38 (d, J = 3 Hz, ArC); 31P NMR
Financial supports of the Hungarian Scientific Research Fund
(OTKA K112289) and the New Széchenyi Development Plan
(TÁMOP-4.2.1/B-09/1/KMR-2010-0002) are gratefully acknowl-
edged. The authors also express their appreciation to Dr. József
Nagy for helpful discussion.
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015

T. Szabó et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
7
23. Izatt, R. M.; Lindh, G. C.; Clark, G. A.; Nakatsuji, Y.; Bradshaw, J. S.; Lamb, J. D.;
Christensen, J. J. J. Membr. Sci. 1987, 31, 1–13.
References
24. Kádár, M.; Bíró, A.; Tóth, K.; Vermes, B.; Huszthy, P. Spectrochim. Acta, A: Mol.
Biomol. Spectrosc. 2005, 62, 1032–1038.
25. Kovács, I.; Huszthy, P.; Bertha, F.; Sziebert, D. Tetrahedron: Asymmetry 2006, 17,
2538–2547.
26. McDaniel, C. W.; Bradshaw, J. S.; Izatt, R. M. Heterocycles 1990, 30, 665–706.
27. Strzelbicki, J.; Bartsch, R. A. J. Membr. Sci. 1982, 10, 35–47.
28. Székely, G.; Csordás, B.; Farkas, V.; Kupai, J.; Pogány, P.; Sánta, Z.; Szakács, Z.;
Tóth, T.; Hollósi, M.; Nyitrai, J.; Huszthy, P. Eur. J. Org. Chem. 2012, 2012, 3396–
3407.
29. Székely, G.; Farkas, V.; Párkányi, L.; Tóth, T.; Hollósi, M.; Huszthy, P. Struct.
Chem. 2010, 21, 277–282.
30. Walkowiak, W.; Brown, P. R.; Shukla, J. P.; Bartsch, R. A. J. Membr. Sci. 1987, 32,
59–68.
31. Huber, V. J.; Ivy, S. N.; Lu, J.; Bartsch, R. A. Chem. Commun. 1997, 1499–1500.
32. Lee, E. K.; Cho, B. R.; Hu, H.; Bartsch, R. A. Anal. Chem. 2002, 74, 2177–2183.
33. Talanova, G. G.; Hwang, H.-S.; Talanov, V. S.; Bartsch, R. A. Anal. Chem. 2001, 73,
5260–5265.
34. Tu, C. Arkivoc 2010, vii, 98–117.
35. Walkowiak, W.; Kang, S. I.; Stewart, L.; Ndip, G.; Bartsch, R. A. Anal. Chem. 1990,
62, 2022–2026.
36. Yang, I. W.; Pugia, M. J.; Bartsch, R. A. Anal. Chem. 1990, 62, 2018–2021.
37. Charewicz, W. A.; Grabowska, J.; Bartsch, R. A. Sep. Sci. Technol. 2001, 36, 1479–
1494.
38. Maciejewski, P.; Ulewicz, M.; Robak, W.; Walkowiak, W. Int. J. Environ. Waste
Manage. 2011, 8, 305.
39. Ulewicz, M.; Walkowiak, W.; Brandt, K.; Porwolik-Czomperlik, I. Sep. Sci.
Technol. 2003, 38, 633–645.
40. Ulewicz, M.; Walkowiak, W.; Jang, Y.; Kim, J. S.; Bartsch, R. A. Anal. Chem. 2003,
75, 2276–2279.
41. Newcomb, M.; Toner, J. L.; Helgeson, R. C.; Cram, D. J. J. Am. Chem. Soc. 1979,
101, 4941–4947.
42. Dhawan, B.; Redmore, D. J. Org. Chem. 1986, 51, 179–183.
43. Lamb, J. D.; Izatt, R. M.; Garrick, D. G.; Bradshaw, J. S.; Christensen, J. J. J. Membr.
Sci. 1981, 9, 83–107.
1. Chen, Z.; Echegoyen, L. In Crown Compounds: Toward Future Applications;
Cooper, S. R., Ed.; VCH: New York, 1992; pp 27–39.
2. Szabó, T.; Hirsch, E.; Tóth, T.; Huszthy, P. Tetrahedron: Asymmetry 2014, 25,
1443–1449.
3. Bartsch, R. A. ACS Symp. Ser. 1999, 716, 146–155.
4. Bartsch, R. A.; Jeon, E.-G.; Walkowiak, W.; Apostoluk, W. J. Membr. Sci. 1999,
159, 123–131.
5. Bradshaw, J. S. J. Inclusion Phenom. Mol. Recognit. Chem. 1997, 29, 221–246.
6. Bradshaw, J. S.; Izatt, R. M.; Huszthy, P.; Nakatsuji, Y.; Biernat, J. F.; Koyama, H.;
McDaniel, C. W.; Wood, S. A.; Nielsen, R. B.; Lindtt, G. C.; Bruening, R. L.; Lamb, J.
D.; Christensen, J. J. Stud. Org. Chem. 1987, 31, 553–560.
7. Brown, P. R.; Bartsch, R. A. In Inclusion Aspects of Membrane Chemistry; Osa, T.,
Atwood, J. L., Eds.; Kluwer Academic: Boston, 1991; pp 1–57.
8. Charewicz, W. A.; Bartsch, R. A. Anal. Chem. 1982, 54, 2300–2303.
9. Charewicz, W. A.; Bartsch, R. A. J. Membr. Sci. 1983, 12, 323–333.
10. Charewicz, W. A.; Heo, G. S.; Bartsch, R. A. Anal. Chem. 1982, 54, 2094–2097.
11. Fyles, T. M.; Malik-Diemer, V. A.; Whitfield, D. M. Can. J. Chem. 1981, 59, 1734–
1744.
12. Gerencsér, J.; Báthori, N.; Czugler, M.; Huszthy, P.; Nógrádi, M. Tetrahedron:
Asymmetry 2003, 14, 2803–2811.
13. Gerencsér, J.; Huszthy, P.; Nógrádi, M. Arkivoc 2004, vii, 7–14.
14. Hriciga, A.; Lehn, J. M. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 6426–6428.
15. Huszthy, P.; Farkas, V.; Tóth, T.; Székely, G.; Hollósi, M. Tetrahedron 2008, 64,
10107–10115.
16. Huszthy, P.; Kertész, J.; Bradshaw, J. S.; Izatt, R. M.; Redd, J. T. J. Heterocycl.
Chem. 2001, 38, 1259–1264.
17. Huszthy, P.; Vermes, B.; Báthori, N.; Czugler, M. Tetrahedron 2003, 59, 9371–
9377.
18. Izatt, R. M.; Lindh, G. C.; Biernat, J. F.; Bochenska, M.; Bruening, R. L.; Bradshaw,
J. S.; Christensen, J. J. J. Inclusion Phenom. Mol. Recognit. Chem. 1989, 7, 487–499.
19. Izatt, R. M.; Lindh, G. C.; Bruening, R. L.; Huszthy, P.; Lamb, J. D.; Bradshaw, J. S.;
Christensen, J. J. J. Inclusion Phenom. 1987, 5, 739–745.
20. Izatt, R. M.; Lindh, G. C.; Bruening, R. L.; Huszthy, P.; McDaniel, C. W.;
Bradshaw, J. S.; Christensen, J. J. Anal. Chem. 1988, 60, 1694–1699.
21. Izatt, R. M.; Lindh, G. C.; Clark, G. A.; Bradshaw, J. S.; Nakatsuji, Y.; Lamb, J. D.;
Christensen, J. J. J. Chem. Soc., Chem. Commun. 1985, 1676.
22. Izatt, R. M.; Lindh, G. C.; Huszthy, P.; Clark, G. A.; Bruening, R. L.; Bradshaw, J. S.;
Christensen, J. J. J. Inclusion Phenom. Mol. Recognit. Chem. 1989, 7, 501–509.
44. Riddick, J. A.; Bunger, W. B.; Sakano, T. K., 4th ed. In Organic Solvents: Physical
Properties and Methods of Purification; Weissberger, A., Ed.; Wiley-Interscience:
New York, NY, 1986; Vol. 2,.
Please cite this article in press as: Szabó, T.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.04.015