New ligands for enantioselective recognition of chiral carboxylates based on 1,1′-binaphthalene-2,2′-diamine

Article abstract of DOI:10.1135/cccc20040365

Simple bis(arylureido)binaphthalenes and (arylamido)binaphthalenes have been synthesized in both racemic as well as optically active forms. One of these compounds has been found to complex chiral anions with modest enantioselectivity.

Full text of DOI:10.1135/cccc20040365

New Ligands for Enantioselective Recognition
365
NEW LIGANDS FOR ENANTIOSELECTIVE RECOGNITION OF CHIRAL
CARBOXYLATES BASED ON 1,1′-BINAPHTHALENE-2,2′-DIAMINE
b
Ivan STIBORa1,*, Roman HOLAKOVSKÝa2, Asiya R. MUSTAFINA and
a3
Pavel LHOTÁK
a
Department of Organic Chemistry, Institute of Chemical Technology, Prague, Technická 5,
166 28 Prague 6, Czech Republic; e-mail: stibori@vscht.cz, roman.holakovsky@vscht.cz,
lhotakp@vscht.cz
A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences,
420088 Kazan, Russia; e-mail: asiya@iopc.knc.ru
1
2
3
b
Received February 7, 2003
Accepted Novem ber 21, 2003
Sim ple bis(arylureido)bin aph th alen es an d (arylam ido)bin aph th alen es h ave been syn th esized
in both racem ic as well as optically active form s. On e of th ese com poun ds h as been foun d
to com plex ch iral an ion s with m odest en an tioselectivity.
Keyw ord s: Biaryls; Bin aph th alen es; Axial ch irality; Ch iral an ion recogn ition ; Com plexation ;
Extraction s; Am ides.
In terest in th e com plexation of an ion ic species con tin ues to attract th e at-
ten tion of th e ch em istry com m un ity as witn essed by n um erous reviews
publish ed recen tly1. Th e im portan ce of an ion s in biological system s is well
recogn ized2, an d th e sam e is true for th e role of an ion s in ch em ical pro-
cesses an d en viron m en tal pollution . Given th eir im portan ce, th ere h as ob-
viously been m uch effort expen ded in th e design of an ion -com plexin g
ligan ds. Th e m ain strategies h ave tradition ally focused on cation ic, poly-
am m on ium , guan idin ium , quatern ary am m on ium , porph yrin -based lig-
an ds, an d a n um ber of Lewis acids con tain in g ligan ds. Neutral organ ic
ligan ds th at bin d an ion s via favourable h ydrogen bon din g h ave also been
studied1,3 by several groups an d also in our laboratory4. Our atten tion h as
been con cen trated on sim ple arom atic an d h eteroarom atic am ides as well
as calixaren e-based ligan ds5. We h ave developed th eoretical m eth ods for
th e prediction of brom ide an ion -bin din g ability of sim ple arom atic
am ides6. We h ave also foun d th at th ese sim ple am ides are able to act
co-operatively. Triam ides derived from tren (tris(2-am in oeth yl)am in e) an d
both pen tafluoroben zoic an d ison icotin ic acids h ave been foun d to com -
plex h ydrogen sulfate an d dih ydrogen ph osph ate with n ice selectivity5. Th at
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20040365

366
Stibor, Holakovský, Mustafina, Lhoták:
is wh y we aim ed to exten d our studies to ch iral, preferably arom atic
scaffolds wh ere several arom atic am ides or ureas could bin d an ion co-
operatively. Obviously, calix[n]aren e an d axially ch iral 1,1′-bin aph th alen e
m olecular scaffolds were assum ed to fulfil th e purpose. Wh ile a n um ber of
calixaren e-based ligan ds for an ion bin din g h as already been publish ed an d
th e calixaren e literature is abun dan t7,8, m uch less is kn own on application
of axially ch iral arom atic skeleton s to an ion recogn ition 9 despite th e fact
th at 1,1′-bin aph th alen e-2,2′-diam in e is com m ercially available in both
en an tiom erically pure form s. Con sequen tly, we report h ere on easily ac-
cessible n ew ch iral n eutral ligan ds based on ch iral 1,1′-bin aph th alen e-2,2′-
diam in e.
RESULTS AND DISCUSSION
Synthesis
Syn th eses of ligan ds were straigh tforward usin g acylation with acid ch lo-
rides or isocyan ates un der stan dard con dition s. Surprisin gly, th e racem ic
1,1′-bin aph th alen e-2,2′-diam in e is n ot com m ercially available an d h as to
be prepared accordin g literature procedures. In our h an ds, th e superior
preparation was th at based on Myian o’s publish ed procedure10. Th e m ain
poin t is th e product purity as th e crude product is accom pan ied by startin g
2-n aph th ylam in e wh ich h as to be wash ed out by th orough extraction of
crude product with h ot water. Racem ic ligan ds 1–3 h ave been prepared in
good to excellen t yields usin g a stan dard acylation procedure in th e pres-
R'
NH
O
O
R
NH
NH
NH
O
NH
O
R
NH
R'
1 - 3
5 - 8
1, R = phenyl
2, R = 3,5-bis(trifluoromethyl)phenyl
3, R = 2,3,4,5,6-pentafluorophenyl
5, R´ = 3,5-bis(trifluoromethyl)phenyl
6, R´ = 4-methylphenyl
7, R´ = 4-nitrophenyl
8, R´ = dodecyl
en ce of trieth ylam in e with th e on ly exception of th e reaction with
perfluoroben zoyl ch loride. Th e “n orm al” am ide 3 can on ly be obtain ed
wh en acylation is perform ed at –78 °C. Th e sam e reaction at am bien t tem -
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

New Ligands for Enantioselective Recognition
367
perature h as furn ish ed tetraacyldiam in e 4 (Sch em e 1) th at h as been fully
ch aracterized in cludin g sin gle-crystal X-ray an alysis (Fig. 1).
O
N
R
O
R
R
R
NH2
NH2
N
N
O
H
H
O
O
+
+
R
Cl
N
O
R
O
R
F
F
F
4
3
F
R =
F
SCHEME 1
Havin g th ese am ides, we h ave perform ed th e prelim in ary NMR titration
experim en ts with brom ide an ion in CDCl3. No ch an ge of ligan d spectra
(1–3) h as been observed goin g from pure ligan d to a ten -fold excess of cor-
respon din g Bu4N+ salt. On th e oth er h an d, it is kn own 3 th at urea fun ction s
usually exh ibit stron ger com plexation abilities towards an ion s if com pared
with th e correspon din g am ides. Con sequen tly, we h ave prepared a series of
ureas 5–8 from both racem ic an d optically pure diam in e an d com m ercially
available isocyan ates.
We h ave foun d th at racem ic ligan ds are m uch less soluble th an optically
pure on es. Wh ereas DMSO was foun d to be th e on ly solven t wh ere con cen -
tration of racem ic ligan ds 5 × 10–4 m ol l–1 can be attain ed, th e optically
FIG. 1
ORTEP view11 of crystal structure of 4 (th erm al ellipsoids are drawn with 50% probability)
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

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Stibor, Holakovský, Mustafina, Lhoták:
pure ligan ds are soluble in ch loroform . As th e stability of com plexes form ed
with an ion in DMSO are too low to be m easured usin g NMR titration , on ly
optically pure com poun ds h ave been used an d th e com plexation studies
were perform ed in CDCl3. Th e ligan d (R)-5 was foun d to be superior to all
th e com poun ds prepared an d was used th rough out th e study.
Complexation
It is a well-kn own fact12 th at substituted ureas spon tan eously associate in
n on -com petitive solven ts. Th at is wh y a dilution experim en t with (R)-5 h as
been perform ed prior to stability con stan t m easurem en t. Th e NMR spec-
trum of th is ligan d was foun d to rem ain un ch an ged (with in ±1 Hz) at a
con cen tration below 10–3 m ol l–1 in CDCl3. Con sequen tly, all m easure-
m en ts h ave been m ade with con cen tration of th e (R)-5 ligan d about
5 × 10–4 m ol l–1 or lower wh ere th e in fluen ce of self-association of th e free
ligan d can be n eglected.
To test th e com plexation ability of th e (R)-5 ligan d, a prelim in ary screen -
in g was carried out with several an ion s represen tin g differen t geom etry.
Hen ce, th e sph erical brom ide, plan ar n itrate an d acetate, an d th e tetrah e-
dral dih ydrogen ph osph ate were used with tetrabutylam m on ium coun ter-
cation s. Usin g a con ven tion al 1H NMR titration experim en t on ly th e 1:1
stoich iom etry (ligan d:an ion ) was foun d. As sh own in Fig. 2, th e in teraction
a
b
FIG. 2
NMR titration experim en t: a free (R)-5, b (R)-5 in th e presen ce of 10 equivalen ts of tetra-
butylam m on ium brom ide in CDCl3
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New Ligands for Enantioselective Recognition
369
of (R)-5 ligan d with Br– leads to large com plexation -in duced ch em ical sh ifts
(CIS) of both NH, an d ortho-ph en yl proton s. Th e association con stan ts ob-
tain ed by a n on -lin ear regression an alysis are sum m arized in Table I.
To gain deeper in sigh t in to th e bin din g ph en om en on , th e com plex of
(R)-5 with tetrabutylam m on ium acetate was studied in CD2Cl2 solution us-
in g a 500 MHz NMR spectrom eter. Th e assign m en t of all sign als (free ligan d
versus ligan d in th e presen ce of 15 equivalen ts of Bu4NAc) allowed us to de-
term in e th e correspon din g com plexation in duced ch em ical sh ifts (Table II).
As eviden ced by large CIS values (CIS[13] = +1955 Hz, CIS[11] = +830 Hz),
both NH groups in urea fun ction s are en gaged in th e com plexation of an -
ion via th e h ydrogen bon din g in teraction s. On th e oth er h an d, th e rem ark-
able differen ce in th e NH sh ifts proves th at th e con tribution of NH group in
position 13 (CIS = 3.91 ppm ) is m uch larger than that in position 11 (CIS =
1.66 ppm ). In terestin gly, th e relatively h igh CIS value for ortho-h ydrogen s
15 (CIS[15] = 0.44 ppm ) in dicates th at th ese h ydrogen s are presum ably also
en gaged in th e com plexation exh ibitin g th e C–H···an ion in teraction s. At th e
sam e tim e, th e sign al of acetate is sh ifted upfield in th e presen ce of (R)-5.
En couraged by th ese results, we h ave decided to exam in e th e ability of
1
(R)-5 to in teract with ch iral carboxylates13. Usin g con ven tion al H NMR ti-
tration experim en t both L- an d D-lactate h ave been foun d to form com plexes
with approxim ately th e sam e stability con stan t 13400 ± 3500 l m ol–1. As
th e addition al π–π in teraction s can be en visaged in arom atic carboxylates,
we h ave focused our atten tion to th e (R)- an d (S)-m an delates. Th e NMR ti-
tration experim en ts proved th e form ation of th e com plexes with very h igh
stability con stan ts, in fact too stable to be reliably studied by NMR (th e esti-
m ated stability con stan t in CDCl3 > 105 l m ol–1). On th e oth er h an d, th e
CIS in DMSO-d6 were n egligible, sh owin g th us th e crucial role of h ydrogen
bon din g in th e com plexation ph en om en on . Un fortun ately, our attem pts to
TABLE I
Association con stan ts (in l m ol–1) of com plexes of (R)-5 with an ion s of tetrabutylam m on ium
salts in CDCl3
An ion
Association con stan t
Brom ide
3360 ± 450
2780 ± 380
Nitrate
Dih ydrogen ph osph ate
Acetate
1110 ± 180
36 500 ± 8800
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370
Stibor, Holakovský, Mustafina, Lhoták:
use UV/VIS spectroscopy in th e com plexation study of m an delates (CHCl3)
were also un successful as n o substan tial ch an ges in UV/VIS spectra were ob-
served durin g th e titration experim en ts.
Th e ch iral recogn ition of m an delates with (R)-5 was studied usin g sim ple
extraction experiments where a chloroform solution of ligand (c = 0.01 mol l–1,
1 m l) was stirred in ten sively (1100 rpm ) with an aqueous solution of
Bu4N+(RS)-m an delate (c = 0.01 m ol l–1, 1 m l) for 1 h . Th e m an delates re-
m ain in g in th e aqueous ph ase after extraction were m on itored by HPLC on
ch iral colum n (Ch iralcel OD-H, isopropan ol:h exan e:TFA = 1:4:trace). Th e
in tegration of th e correspon din g peaks in ch rom atogram revealed th at th e
(R)-m an delate is better extracted th an (S)-m an delate (S:R = 4:6) wh ile th ere
were n o en an tioselectivity in th e “backgroun d experim en t” wh ere n o li-
gan d was used in th e organ ic layer. Th is experim en t revealed, th at th e (R)-5
ligan d can be used in th e recogn ition an d com plexation of ch iral an ion s.
To specify th e stoich iom etry of com plexes form ed by th e (R)-5 ligan d
with an ion s, an d with ch iral carboxylates in particular, we h ave perform ed
an extraction study (D2O/CDCl3) of an ion s usin g (R)-5 ligan d. Th e progress
TABLE II
1H NMR ch em ical sh ifts (500 MHz) for (R)-5 both free an d com plexed (15-fold excess of
Bu4NAc) in CD2Cl2 an d CIS values
18
CF3
8
5
1
11
NH
12
2
9
7
6
17
3
O
13
N
H
10
14
16 CF3
4
15
Free ligan d
Com plexed ligan da
Position
∆δ, Hz
δ, Hz
δ, Hz
3
4
4001
4057
3952
3725
3616
3504
3463
3746
3798
3707
3994
4031
3958
3701
3611
3520
4293
5701
4017
3669
–7
–26
5
+6
6
–24
7
–5
8
+16
11
13
15
17
+830
+1955
+219
–38
a
15 equivalen ts of Bu4NAc added.
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New Ligands for Enantioselective Recognition
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of extraction was m on itored by 1H NMR spectroscopy usin g th e well re-
solved sin glet of four ortho-h ydrogen s of 3,5-bis(trifluorom eth yl)ph en yl
groups (aroun d δ 7.73). Two procedures h ave been ch osen to describe th e
com plexation in volved. Firstly, th e down field sh ifts of ortho-proton s caused
by th e com plexation of an ion s were plotted again st Cg/Ch wh ere Cg is th e
con cen tration of an ion in aqueous ph ase an d Ch is th e con cen tration of
(R)-5 ligan d in organ ic ph ase. Th e curves obtain ed were used to evaluate
th e extractability of an ion s by th e ligan d (R)-5 (Fig. 3). Wh ile th e ben zoate
clearly correspon ds to th e form ation of 1:1 com plex, th e stoich iom etry of
a
0.4
0.3
0.2
0.1
0.0
0
2
4
6
8
C /C
g
h
0.4
0.3
b
0.2
0.1
0.0
0
2
4
6
8
C /C
g
h
FIG. 3
Plot of th e observed sh ift of ortho-proton , ∆δ, again st Cg/Ch (Ch , con cen tration of ligan d in
CDCl3 ph ase; for oth er sym bols, see Sym bols). a Ben zoate (᭜), (S)-lactate (᭹); b acetate (᭜),
(RS)-m an delate (᭹)
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372
Stibor, Holakovský, Mustafina, Lhoták:
oth er com plexes sh own in Fig. 3 is less obvious. Presum ably, m ore th an 1:1
stoich iom etry is in volved in th e com plexation .
Secon dly, a log–log plot14 (see Experim en tal) was con structed an d results
are sum m arized in Figs 4 an d 5. Both Kex an d th e com plex stoich iom etry
un der saturation con dition s can be evaluated usin g th is m eth od.
1.5
1.0
0.5
0.0
–0.5
–1.0
–4
–3
–2
–1
log (C – αC )
g
h
FIG. 4
Log–log an alysis14 of extraction data for ach iral an ion s (Ch , con cen tration of ligan d in CDCl3
ph ase; for oth er sym bols, see Sym bols). An ion s: brom ide (᭜), acetate (᭿), ben zoate (ꢀ)
1.0
0.5
0.0
–0.5
–3.0
–2.5
–2.0
–1.5
log (C – αC )
g
h
FIG. 5
Log–log plot14 of extraction data for lactates an d m an delates usin g (R)-5. For defin ition of
sym bols, see Sym bols. An ion s: (RS)-m an delate (᭜), (S)-m an delate (᭿), (R)-m an delate (ꢀ),
(R)-lactate (-), (RS)-lactate (–), (S)-lactate (᭹)
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New Ligands for Enantioselective Recognition
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Th e followin g im portan t con clusion s can be drawn from th ese data. Both
brom ide an d ben zoate h ave been foun d to form 1:1 com plexes un der all
th e con dition s used. Acetate gave less clear results. Th e ligan d:an ion stoi-
ch iom etry 1:2 seem s to be m ore probable, but it is eviden t th at saturation is
ach ieved at a very h igh excess of an ion an d th e com plexation is likely to
proceed in two steps. Un fortun ately, an accurate evaluation of th e first-step
com plexation data can n ot be ach ieved due to sim ultan eous saturation of
both 1:1 an d 1:2 com plexes. Th e ∆δ of ortho-proton s sligh tly in creased go-
in g from brom ide to acetate (0.315 to 0.334 ppm in water-saturated ch loro-
form ), wh ich is in accordan ce with th e data in Table I. Th e upfield ∆δ for
proton s in position s 3, 4, an d 6 of th e bin aph th alen e skeleton are h igh er
goin g from brom ide to acetate. It can be in terpreted as two-poin t bin d-
in g of acetate to on e urea un it in con trast to brom ide wh ere an ion is co-
operatively boun d in th e cleft form ed by both un its. More precise stability
con stan ts for acetate an d ben zoate in water-saturated ch loroform could n ot
be obtain ed due to overlap of ortho-proton s with proton s in position s 3, 4,
1
an d 6 in 300 MHz H NMR spectra. Goin g from acetate to ben zoate th e up-
field sh ift in creases wh ile bin din g of on e ben zoate an ion resulted in a
h igh er ∆δ of proton 15 th an th e bin din g of two acetate an ion s. Takin g in to
accoun t th e 1:1 stoich iom etry an d th e in creased efficien cy of ben zoate ex-
traction it can be proposed th at th e efficien t ben zoate com plexation occurs
via four-poin t cleft-like bin din g of ben zoate an ion with all four N–H groups
of both ureas of th e ligan d an d arom atic stackin g in teraction of th e ben zo-
ate with bis(trifluorom eth yl)ph en yl m oieties. Th is is in lin e with th e in -
creased value of th e ∆δ.
Extraction s of lactates are sim ilar to th ose of acetate. Com plexation also
appears to be stepwise with a 1:2 stoich iom etry un der saturated con dition s
(Fig. 3). Th e log–log plots for both lactates an d ben zoates are sh own in
Fig. 4. Th e presen ce of h ydroxy group does n ot result in a m ore efficien t
com plexation , but in predom in an t com plexation of (R)-lactate with a rath er
h igh KR/KS ratio bein g n early 4 (see Table III), wh ich is in stron g con tradic-
tion with th e two-poin t bin din g via carboxylate oxygen s. Th e an alysis of
spectra of both th e com plexes in dicate th at th e bin din g of (R)-lactate re-
sults in h igh er up-field sh ifts of bin aph th alen e proton s, wh ile th e ∆δ of pro-
ton 15 is lower th an th at of (S)-lactate. It is th erefore possible to propose,
th at (R)-lactate is predom in an tly boun d via its carboxylate oxygen to
13-NH groups an d lactate h ydroxyl with 11-NH groups wh ile (S)-lactate is
likely to be boun d in versely. It is im portan t to stress th at both bin din g sites
of (R)-5 beh ave in th e sam e way.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

374
Stibor, Holakovský, Mustafina, Lhoták:
Both th e stability con stan ts Kex an d CIS values of th e racem ic lactate h ave
been foun d to lie between th ose for R an d S isom ers (Table III).
It is also apparen t th at both lactates an d m an delates are com plexed with
a very sim ilar stoich iom etry, differen t from th ose of brom ide an d ben zoate
(1:1) an d very close to th at of acetate (stepwise 1:1 an d 1:2). A com parison
of extraction data for lactate an d m an delate sh ould also reveal th e effect of
arom atic h ost–guest in teraction s on th e com plex form ation . From practical
poin t of view, due to th e presen ce of arom atic rin gs, th e extraction can be
m on itored by com bin ation of NMR (in ch loroform solution ) an d UV spec-
tra (aqueous ph ase). Accordin g to th e NMR data, th e extraction of m an de-
lates results in both th e down field sh ift of proton 15 an d th e upfield sh ift
of proton s 3, 4, an d 6. Th e an alysis of ∆δ data by log–log plot (Fig. 5) in di-
cates th at m an delates form com plexes with m uch h igh er stability com -
pared with lactate. But th e ∆δ values of proton 15 are lower for all m an de-
late m easurem en ts th an th ose for acetate an d lactate (Table III). Even m ore
in terestin gly, th e ∆δ value is th e h igh est for S isom er, decreasin g in th e fol-
lowin g order S > RS > R, wh ile th e com plexation con stan ts decrease in th e
order RS > S > R (Table III). It is rath er un expected th at goin g from lactate to
m an delate, followin g profoun d ch an ges h ave been foun d: (i) in version of
S
en an tioselectivity; (ii) decrease in en an tioselectivity (KexR/Kex is n early 4
R
for lactate, wh ile KexS/Kex is 1.3 for m an delate); (iii) stability of com plexes
TABLE III
Extraction data for (R)-5 an ion from water to ch loroform m on itored by 1H NMR spectra
Ligan d:an ion
stoich iom etry
log Kex
An ion
CIS, ppm
Ben zoate
1:1
1:1
1:2
1:2
1:2
1:2
1:2
1:2
1:2
3.60 ± 0.1a
2.40 ± 0.05a
4.10 ± 0.08b
4.60 ± 0.07b
3.96 ± 0.06b
4.36 ± 0.05b
6.5 ± 0.1b
0.402
0.316
0.334
0.305
0.346
0.315
0.273
0.236
0.250
Brom ide
Acetate
(R)-Lactate
(S)-Lactate
(RS)-Lactate
(S)-Man delate
(R)-Man delate
(RS)-Man delate
6.4 ± 0.1b
6.7 ± 0.1b
a
b
Com plexation con stan t Kex (in l m ol–1) for 1:1 com plexation process.
Th e overall
com plexation con stan t (in l2 m ol–2) for 1:2 stoich iom etry.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

New Ligands for Enantioselective Recognition
375
form ed (1:2 stoich iom etry) are in creasin g in th e order R < S < RS for
m an delates, wh ile th e order for lactate is R > RS > S.
In order to better un derstan d wh at is goin g on with m an delates, we h ave
followed th eir extraction with (R)-5 un der th e con dition s of 1:1 bin din g
(i.e. m olar excess of ligan d (R)-5 to m an delates) as a fun ction of th e ligan d:
an ion ratio. Th e extraction of m an delates was studied by UV-VIS in th e
con cen tration region 0.0022–0.012 m ol l–1, wh ile th e con cen tration of (R)-5
in organ ic ph ase (Ch ) was kept un ch an ged at 0.009 m ol l–1. Th e depen d-
en ces of extraction exten t (evaluated as E = [Man d]/CMan d, wh ere [Man d] is
equilibrium con cen tration of m an delate in aqueous ph ase, CMan d is in itial
con cen tration ) on th e CMan d were m easured. Th e data obtain ed are sum m a-
rized in Table IV.
TABLE IV
Extraction a of m an delates as a fun ction of th e (R)-5:m an delate ratio followed by UV/VIS
spectrom etry
An ion
CMan db, m ol l–1
[Man d]c, m ol l–1
Kexd, l m ol–1
(S)-Man delate
0.002064
0.003096
0.004128
0.00516
0.00619
0.00722
0.00139
170
183
200
209
217
210
0.002094
0.002823
0.003602
0.00443
0.005313
(R)-Man delate
0.00337
0.00510
0.00683
0.00816
0.00874
0.00245
0.0035
143
183
173
178
168
0.00513
0.00620
0.00690
(RS)-Man delate
0.0027
0.0023
0.0019
0.00315
0.0033
0.00425
154
186
204
436
549
0.00338
0.0047
0.00541
0.00679
a
Con cen tration of (R)-5 (Ch ) was 0.009 m ol l–1 in all m easurem en ts, con cen tration of m an -
delate was varied with in th e con cen tration ran ge 0.0022–0.012 m ol l–1
cen tration of m an delate in aqueous ph ase. [Man d], equilibrium con cen tration of m an de-
.
CMan d, in itial con -
b
c
d
late in aqueous ph ase. Kex, com plexation con stan ts com puted for 1:1 stoich iom etry; exper-
im en tal errors are with in ±10%, but data given above are reproducible better th an ±5%.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

376
Stibor, Holakovský, Mustafina, Lhoták:
We assum e th at th e prevailin g stoich iom etry of com plexes form ed is 1:1
provided th e con cen tration of th e guest an ion is below 0.01 m ol l–1 (ligan d:
an ion = 1:1 or less). It is eviden t (con fer Table IV) th at furth er in creasin g of
th e m an delate con cen tration (CMan d) leads to an in crease in extraction con -
stan ts. Th is clearly in dicates th at th e secon d step (1:2 bin din g) affects sub-
stan tially th e overall Kex value. Neverth eless, a com parison of th e extrac-
tion con stan ts, com puted from th e h igh est ligan d:an ion ratios, in dicates
th at th e RS-en an tioselectivity (th e ratio of KexS/KexR) of th e 1:1 extraction is
very sim ilar to th ose obtain ed from NMR data for th e 1:2 extraction . Th e
1:1 extraction con stan t of (RS)-m an delate lies between th e values for (S)-
an d (R)-m an delate, wh ile th e 1:2 extraction of (RS)-m an delate is n oticeably
m ore efficien t th an th ose of (S)- an d (R)-m an delate (con fer Table IV). Th us,
(R)-5 extracts (RS)-m an delate in two steps: th e first step proceeds with th e
extraction con stan t bein g between th ose for R an d S isom ers, wh ich in turn
in dicates th at th e extraction efficien cy is determ in ed by th e com petition of
R an d S isom ers for com plexation with (R)-5, th e secon d step seem s to be th e
m ost efficien t for sim ultan eous bin din g of (RS)-m an delate. In terestin gly,
th e com parison of 1:1 an d 1:2 bin din g con stan ts sh ows en h an ced allosteric
effect in dicatin g th at th e com plexation of th e first m an delate suitably
preorgan ises th e m olecule for th e in teration s with th e secon d an ion .
Th e m ain problem is th e differen ce between th e bin din g m odes of lactate
an d m an delate. Based on all th e data obtain ed, n am ely th e arom atic stack-
in g in teraction foun d for ben zoates, an d th e ∆δ value of proton 15 (lower
for m an delates th an th ose for lactates), we propose th at 13-NH groups are
in con tact with h ydroxy groups of m an delate, wh ile 11-NH groups with
carboxylate oxygen s. Accordin g to th is proposal th e m ore efficien t bin din g
of S isom er sh ould be explain ed by m ore efficien t arom atic in teraction s,
wh ich in turn leads to th e ∆δ value for th e com plex with S isom er h igh er
th an th at for th e com plex with R isom er. Th e m ain drivin g force for th is
kin d of bin din g are th e arom atic stackin g in teraction s between electron -
rich ph en yls of m an delate an d electron -deficien t 3,5-bis(trifluorom eth yl)-
ph en yls of th e ligan d.
We h ave also exam in ed th e tran sport of ch iral an ion s (m an delate) across
th e liquid (ch loroform ) m em bran e by m ean s of (R)-5. We h ave foun d th at
th e ligan d studied is n ot suitable for th is application as its presen ce in th e
ch loroform m em bran e slowed down th e tran sport profoun dly if com pared
with a blin d experim en t. Th is is probably due to h igh stability of (R)-5–
m an delate com plex.
In con clusion , we h ave prepared several ch iral ligan ds based on com m er-
cially available 1,1′-bin aph th alen e-2,2′-diam in e. Its urea derivatives h ave
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

New Ligands for Enantioselective Recognition
377
been foun d to form com plexes with an ion s. On e of th em , (R)-5, h as been
th orough ly studied an d foun d to com plex lactate with m odest en an tio-
selectivity. In verse selectivity h as been foun d for m an delate. An explan a-
tion based on NMR, UV, an d extraction beh avior of th e com plexes form ed
in solution h as been suggested.
EXPERIMENTAL
Tem perature data are n ot corrected, m eltin g poin ts were m easured on a Kofler block, optical
rotation s were m easured on a digital polarim eter Jasco DIP370. Specific rotation s [α ]2D0 are
given in 10–1 deg cm 2 g–1 an d con cen tration s are given in g/100 m l. UV spectra were m ea-
sured on a Hewlett Packard 8452A diode array UV spectrom eter. 1H NMR an d 13C NMR
spectra were m easured on a Varian Gem in i 300 HC with 300.075 MHz an d on a Bruker 500
with 500.132 MHz for 1H. Ch em ical sh ifts δ are given in ppm referen ced to tetram eth yl si-
lan e as in tern al stan dard. Couplin g con stan ts J are given in Hz. Th e solven t used is given
with spectral data. Th in layer ch rom atograph y (TLC) was perform ed on com m ercial plates
with Silica gel 60 F254 (Merck). Silica gel 60 (Merck) was used for (flash ) colum n ch rom atog-
raph y. HPLC an alyses were perform ed usin g a HPLC pum p LCP4010 (Pikron ) equipped with
a UV detector LCD 2082 (Ecom ). Th e colum n s with ch iral station ary ph ases were com m er-
cial Ch iralpak OP+ (Daicel) an d Ch iralcel-ODH. Separation con dition s are given for each
case. Reaction s are typically perform ed at am bien t tem perature. Evaporation s in vacuo were
perform ed un der a pressure of 0.67 kPa at 50 °C. Ch em icals were used as obtain ed from
Aldrich , Fluka, Merck an d Lan caster in an alytical grade quality. Dich lorom eth an e was dis-
tilled from calcium h ydride; trieth ylam in e was distilled from KOH pellets an d stored over
m olecular sieves 4 Å.
X-Ray Measurem en t
X-Ray data for 4: C34H14F10N2O2, M = 672.481, orth orh om bic system , space group P21221,
a = 12.024(1), b = 12.3331(7), c = 14.154(3) Å, V = 2098.9(5) Å3, Z = 2, Dc = 1.0640 g cm –3
,
µ(CuKα) = 8.576 cm –1, a colorless crystal of dim en sion s of 0.1 × 0.3 × 0.3 m m . Data were
m easured at 293 K on an En raf–Non ius CAD4 diffractom eter with graph ite-m on och rom atized
CuKα radiation . Th e structure was solved by direct m eth od15 an d refin ed (oxygen , fluorin e
an d n itrogen atom s an isotropically an d carbon atom s isotropically) by full-m atrix least-
squares on F values16 to fin al R = 0.0709, Rw = 0.0738 an d S = 1.0962 with 216 param eters
usin g 2557 in depen den t reflection s (θran ge = 3.58–59.94°). Hydrogen atom s lin ked to carbon
atom s were located from th e expected geom etry an d were n ot refin ed. CCDC 201671 con -
tain s th e supplem en tary crystallograph ic data for th is paper. Th ese data can be obtain ed free
of ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from th e Cam bridge Crystallo-
graph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax: +44 1223 336033; or
deposit@ccdc.cam .ac.uk).
Stability Con stan ts Measurem en ts
1H NMR spectroscopy: Typically, a stock solution of ligan d in CDCl3 an d a stock solution
of an ion (as tetrabutylam m on ium salt in th e sam e solven t) were m ixed in an NMR tube
(diluted with pure solven t) to obtain th e fin al con cen tration of ligan d 0.0005 m ol l–1. Th e
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

378
Stibor, Holakovský, Mustafina, Lhoták:
an ion am oun ts used were: 0.1; 0.2; 0.3; 0.4; 0.5; 0.6; 0.7; 0.8; 0.9; 1.0; 1.1; 1.2; 1.3; 1.4; 1.5;
1.6; 1.7; 1.8; 1.9; 2.0; 2.5; 3.0; 3.5; 4.0; 4.5; 5.0 a 10.0 m olar equivalen ts. ∆δ data for all pro-
17
ton s sh ifted were obtain ed an d used as in put for program m e OPIUM
stan ts an d CIS values for given stoich iom etry of th e com plexes form ed.
givin g stability con -
Extraction Meth od
Single extraction – HPLC assessment. A solution of ligand in chloroform (c = 0.01 m ol l–1, 1 m l)
was stirred m agn etically (1100 rpm ) with an aqueous solution of tetrabutylam m on ium (RS)-
m an delate (c = 0.01 m ol l–1, 1 m l) for 1 h . Th e aqueous ph ase was separated, th e organ ic
ph ase was evaporated in vacuo, redissolved in propan -2-ol (1 m l) an d th e solution th us ob-
tain ed was subjected to HPLC an alysis. Th e backgroun d effect was assessed in th e sam e ex-
perim en t but with n o ligan d.
Extraction – log–log procedure14. It is kn own th at Kex can be calculated based on extraction
experim en t as: Kex = α(1 – α)–1(Cg – αCh )–1 for th e 1:1 com plex (ligan d:an ion ) stoich iom etry
an d in m ore gen eral term s as: Kex = α(1 – α)–1(Cg – αCh )–n for th e 1:n com plex stoich io-
m etry. All th ese sim plified equation s are based on assum ption th at th e com plex [(R)-5–
an ion ] exists on ly in organ ic (ch loroform ) ph ase.
In logarith m ic form we obtain :
log Kex = log α(1 – α)–1 – n log (Cg – αCh ) ,
wh ere α is an exten t of com plexation in th e organ ic ph ase, defin ed as: α = (∆δ) CIS–1; q =
α(1 – α)–1; fin ally (Cg – αCh ) is equilibrium con cen tration of un com plexed an ion in th e
aqueous ph ase.
By plottin g experim en tally accessible log q again st log (Cg – αCh ) a straigh t lin e sh ould be
obtain ed. Its slope an d in tercept are n (stoich iom etry of th e com plex) an d log Kex, respec-
tively.
The extraction procedure – UV spectroscopy assessment (for mandelate only). Equilibrium con -
cen tration of Bu4N m an delate was m easured as follows. A ligan d solution (0.009 m ol l–1
,
2 m l) in ch loroform was m ixed with 5 m l of aqueous Bu4N+m an delate– of con cen tration
in th e ran ge 0.002–0.012 m ol l–1. After stirrin g for 1 h an d ph ase separation , th e con cen tra-
tion s of m an delate were determ in ed by UV spectroscopy both in aqueous an d ch loro-
form solution s from th e m easured absorban ce an d absorption coefficien t accordin g to th e
Lam bert–Beer law at 260 n m .
The extraction procedure – 1H NMR spectroscopy assessment (for mandelate only). Th e gen eral
extraction procedure was as follows: a ch loroform (CDCl3) solution of ligan d (0.0089 m ol l–1
,
1 m l) was stirred for 60 m in with 1 m l of aqueous (D2O) solution of tetrabutylam m on ium
salts. Con cen tration of th e salts varied from 0.003 to 0.03 m ol l–1. Th e exten t of com plex-
ation was estim ated from NMR spectroscopy data usin g α = ∆δ/CIS.
Tran sport Eexperim en ts
Th ese experim en ts were carried out in th e tran sport cell with th e design based on th at in lit-
erature18. Th e liquid m em bran e was a ch loroform solution of ligan d (0.009 m ol l–1), th e
source ph ase was aqueous solution of Bu4N m an delate (0.0045 m ol l–1), an d th e receivin g
ph ase was redistilled water. Th e volum e of ch loroform ph ase was 10 m l, th e volum e of both
aqueous source an d receivin g ph ases was 2 m l. Th e equilibrium con cen tration of Bu4N
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

New Ligands for Enantioselective Recognition
379
m an delate was estim ated spectroph otom etrically from m easured absorban ces an d absorption
coefficien t accordin g to th e Lam bert–Berr law at 260 n m .
Th e aqueous receivin g an d source ph ases were also an alysed by HPLC. In th is case,
a 1.8 m l aliquot of th e aqueous ph ase was evaporated, th en dissolved in 0.5 m l of propan -
2-ol an d directly an alysed by HPLC (th e HPLC con dition s were sim ilar to th ose used for
Bu4N m an delate).
1,1′-Bin aph th alen e-2,2′-diam in e
2-Naph th ol (40.0 g, 0.277 m ol) an d h ydrazin e m on oh ydrate (7.2 m l, 0.14 m ol) h ave been
h eated to 170–180 °C for 48 h . Th e solid obtain ed was m elted on steam bath , tran sferred to
a m ixture of 300 m l of con cen trated HCl an d 300 m l of water, boiled for several m in utes
an d th e supern atan t was decan ted. Th is procedure was repeated th ree tim es with 300 m l of
dilute HCl (1:1). Com bin ed acid solution s were cooled to am bien t tem perature an d carefully
m ade alkalin e (ice-water bath ) by addition of NaOH pellets. Th e suspen sion th us obtain ed
was h eated to reflux for several m in utes an d th e solid was separated by filtration . Water
(500 m l) was added, boiled for several m in utes an d again filtered wh ile h ot. Th is procedure
was repeated un til n o 2-am in on aph th alen e was presen t in h ot solution . Th e crude product
was dissolved in 2 M HCl (400 m l), th e h ot solution was treated with ch arcoal, filtered an d
th e product precipitated by addition of 10% aqueous NaOH to alkalin e reaction . Th e solid
was collected by filtration , wash ed with water an d dried in air at 60 °C. Pure 1,1′-bi-
n aph th alen e-2,2′-diam in e (10.5 g, 27%) was obtain ed as wh ite powder, m .p. 192–193 °C.
1H NMR (CDCl3): 3.69 (s, 4 H, NH2); 7.08–7.27 (m , 6 H, ArH); 7.78–7.82 (m , 4 H, ArH).
(R)-2,2′-Diben zam ido-1,1′-bin aph th alen e ((R)-1)
Ben zoyl ch loride (107 m g, 0.088 m l, 0.756 m m ol) in dry dich lorom eth an e (12 m l) was
added dropwise to solution of (R)-1,1′-bin aph th alen e-2,2′-diam in e (100 m g, 0.35 m m ol) an d
dry trieth ylam in e (0.75 m l) in dich lorom eth an e (4 m l) at am bien t tem perature overn igh t.
Th e reaction was quen ch ed with 20 m l of diluted HCl (10%), an d th e m ixture was extracted
wash ed with saturated aqueous NaHCO3 (20 m l) an d water (20 m l). Organ ic layer was dried
with an h ydrous MgSO4, evaporated in vacuo leavin g th e crude product (281 m g). Colum n
ch rom atograph y (silica gel, ch loroform :m eth an ol 98:2) furn ish ed pure am ide as yellowish
powder. Yield 170 m g (98%), m .p. 195–196 °C, [α ]2D0 +62.04 (c 0.751, ch loroform ). For
C
34H24N2O2 (492.6) calculated: 82.91% C, 4.91% H, 5.69% N; foun d: 82.87% C, 4.96% H,
5.67% N. 1H NMR (CDCl3): 6.85 (s, 2 H, NH); 6.86–8.77 (m , 22 H, ArH).
(R)-2,2′-Bis{[3,5-bis(trifluorom eth yl)ben zoyl]am in o}-1,1′-bin aph th alen e ((R)-2)
Th e com poun d was prepared from (R)-1,1′-bin aph th alen e-2,2′-diam in e (100 m g, 0.35 m m ol)
an d 3,5-bis(trifluorom eth yl)ben zoyl ch loride (213 m g, 0.77 m m ol) usin g th e sam e procedure
as described for (R)-1. Yield 210 m g (78%), m .p. 203–204 °C, [α ]2D0 +69.86 (c 0.814, ch loro-
form ). For C38H20F12N2O2 (764.6) calculated: 59.70% C, 2.64% H, 29.82% F, 3.66% N;
foun d: 59.67% C, 2.67% H, 29.78% F, 3.67% N. 1H NMR (CDCl3): 7.09 (s, 2 H, NH);
7.23–7.40 (m , 4 H, ArH); 7.33 (s, 2 H, ArH); 7.60 (t, 2 H, ArH, J = 8.2); 7.78 (s, 4 H, ArH);
8.00 (d, 2 H, ArH, J = 8.8); 8.08 (d, 2 H, ArH, J = 8.2); 8.28 (d, 2 H, ArH, J = 8.8).
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

380
Stibor, Holakovský, Mustafina, Lhoták:
(R)-2,2′-Bis[(pen tafluoroben zoy)lam in o]-1,1′-bin aph th alen e ((R)-3)
To (R)-1,1′-bin aph th alen e-2,2′-diam in e (100 m g, 0.35 m m ol) an d dry trieth ylam in e (0.75 m l)
in dry dich lorom eth an e (7.5 m l), a solution of pen tafluoroben zoyl ch loride (355 m g,
0.213 m l, 0.77 m m ol) in dry dich lorom eth an e (12 m l) was added dropwise at –78 °C. Th e
reaction m ixture was set aside for 12 h an d isolated as above yieldin g th e crude am ide
(203 m g) an d, after ch rom atograph y (silica gel, ch loroform ), 97 m g (41%) of pure product,
m .p. 162–163 °C, [α ]2D0 +46.43 (c 1.00, ch loroform ). For C34H14F10N2O2 (672.5) calculated:
60.73% C, 2.10% H, 28.25% F, 4.17% N; foun d: 60.71% C, 2.12% H, 28.15% F, 4.14% N.
1H NMR (CDCl3): 6.51 (d, 2 H, ArH, J = 8.8); 6.94 (t, 2 H, ArH, J = 7.1); 7.29 (s, 2 H, NH); 7.51
(t, 2 H, ArH, J = 8.2); 7.62 (d, 2 H, ArH, J = 8.8); 8.00 (d, 2 H, ArH, 8.2); 8.14 (d, 2 H, ArH,
J = 8.8).
(R)-2,2′-Bis[bis(pen tafluoroben zoyl)am in o]-1,1′-bin aph th alen e ((R)-4)
Th e sam e procedure as for (R)-3 perform ed at –20 °C h as furn ish ed 85 m g (42%), m .p.
144–145 °C, [α ]2D0 62.21 (c 0.655, ch loroform ). For C48H12F20N2O4 (1060.6) calculated:
54.36% C, 1.14% H, 35.83% F, 2.64% N; foun d: 54.34% C, 1.16% H, 35.79% F, 2.63% N.
1H NMR (CDCl3): 6.52 (d, 2 H, ArH, J = 8.2); 6.94 (t, 2 H, ArH, J = 8.2); 7.52 (t, 2 H, ArH, J =
7.1); 7.63 (d, 2 H, ArH, J = 8.8); 8.01 (d, 2 H, ArH, J = 8.2); 8.15 (d, 2 H, ArH, J = 9.3).
2,2′-Bis(N-arylureido)-1,1′-bin aph th alen es. Gen eral Procedure19
1,1′-Bin aph th alen e-2,2′-diam in e (150 m g, 0.53 m m ol) in dry dich lorom eth an e (45 m l) was
treated with aryl isocyan ate (3.7 equivalen ts per NH2 group) at am bien t tem perature for
12 h . Th e reaction was quen ch ed with 10 m l m eth an ol an d stirred for an oth er 12 h . Th e re-
action m ixture was evaporated in vacuo an d purified by colum n ch rom atograph y on silica
gel eluted with ch loroform . Th e product is gen erally eluted as secon d UV-active com poun d.
2,2′-Bis{N-[3,5-bis(trifluoromethyl)phenyl]ureido}-1,1′-binaphthalene (5). Yield 370 m g (88%),
m .p. > 360 °C. For C38H22F12N4O2 (794.6) calculated: 57.44% C, 2.79% H, 28.69% F, 7.05% N;
foun d: 57.41% C, 2.84% H, 28.67% F, 7.02% N. 1H NMR (DMSO-d6): 6.83 (d, 2 H, ArH, J =
8.2); 7.28 (t, 2 H, ArH, J = 7.7); 7.42 (s, 2 H, ArH); 7.45 (t, 2 H, ArH, J = 7.1); 7.48 (s, 2 H,
NH); 7.81 (s, 4 H, ArH); 8.05 (d, 2 H, ArH, J = 7.7); 8.14 (d, 2 H, ArH, J = 7.7); 8.35 (d, 2 H,
ArH, J = 8.8); 9.61 (s, 2 H, NH).
(R)-2,2′-Bis{N-[3,5-bis(trifluoromethyl)phenyl]ureido}-1,1′-binaphthalene ((R)-5). Yield 395 m g
(98%), m .p. 128–130 °C, [α ]D20 136.4 (c 1.00, m eth an ol). For C38H22F12N4O2 (794.6) calcula-
ted: 57.44% C, 2.79% H, 28.69% F, 7.05% N; foun d: 57.40% C, 2.82% H, 28.67% F, 7.03% N.
1H NMR (CDCl3): 6.72 (s, 2 H, NH); 7.02 (d, 2 H, ArH, J = 8.2); 7.28 (t, 2 H, ArH, J = 7.1);
7.42 (s, 2 H, ArH); 7.47 (t, 2 H, ArH, J = 6.6); 7.69 (s, 4 H, ArH); 7.95 (d, 2 H, ArH, J = 8.2);
8.07 (d, 2 H, ArH, J = 8.8); 8.27 (d, 2 H, ArH, J = 9.3); th e oth er NH overlapped with ch loro-
form .
2,2′-Bis(N-p-tolylureido)-1,1′-binaphthalene (6). Yield 170 m g (88%), m .p. 282–284 °C. For
C
36H30N4O (550.7) calculated: 78.52% C, 5.49% H, 10.17% N; foun d: 78.49% C, 5.52% H,
10.14% N. 1H NMR (DMSO-d6): 2.19 (s, 6 H, CH3); 6.77 (d, 2 H, ArH, J = 8.2); 6.97–7.40 (m ,
14 H, 12 ArH an d 2 NH); 7.98 (d, 2 H, ArH, J = 8.2); 8.09 (d, 2 H, ArH, 8.8); 8.62 (d, 2 H,
ArH, J = 8.8); 8.96 (s, 2 H, NH).
2,2′-Bis[N-(4-nitrophenyl)ureido]-1,1′-binaphthalene (7). Yield 125 m g (58%), m .p. > 360 °C.
For C34H24N6O6 (612.6) calculated: 66.66% C, 3.95% H, 13.72% N; foun d: 66.62% C, 3.98% H,
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

New Ligands for Enantioselective Recognition
381
13.70% N. 1H NMR (DMSO-d6): 6.81 (d, 2 H, ArH, J = 8.2); 7.26 (t, 2 H, ArH, J = 7.7); 7.43
(d, 4 H, ArH, J = 8.8); 7.66–8.22 (m , 12 H, 10 ArH an d 2 NH); 8.38 (d, 2 H, ArH, J = 9.3);
9.58 (s, 2 H, NH).
2,2′-Bis(N-dodecylureido)-1,1′-bin aph th alen e (8)
2,2′-Diisocyanato-1,1′-binaphthalene20. 1,1′-Bin aph th alen e-2,2′-diam in e (78 m g, 0.274 m m ol)
was dissolved in diph en yl eth er (10 m l) at 50 °C, th e resultin g solution was treated with
bis(trich lorom eth yl) carbon ate (54.3 m g, 0.183 m m ol) an d th e reaction m ixture was stirred
at 150 °C for 6 h . Th e cold solution was used with out furth er purification in th e subsequen t
reaction .
A solution of dodecylam in e (80 m g, 0.43 m m ol) in dich lorom eth an e (5 m l) was added
an d th e resultin g m ixture was stirred for 12 h . Th e reaction m ixture was purified by colum n
ch rom atograph y. Diph en yl eth er was recovered by elution with ch loroform :petroleum eth er
(1:1) followed by th e product (ch loroform ). Yield 147 m g (76%), m .p. 174–176 °C. For
C
46H66N4O2 (707.1) calculated: 78.14% C, 9.41% H, 7.92% N; foun d: 78.11% C, 9.43% H,
7.89% N. 1H NMR (CDCl3): 0.88 (t, 6 H, CH3, J = 6); 1.25 (m , 40 H, CH2); 2.95 (t, 4 H, CH2,
J = 6); 6.35 (s, 2 H, NH); 7.00 (d, 2 H, ArH, J = 8.3); 7.23 (t, 2 H, ArH, J = 7.1); 7.29 (s, 2 H,
NH); 7.40 (t, 2 H, ArH, J = 8.3); 7.89 (d, 2 H, ArH, J = 8.2); 7.98 (d, 2 H, ArH, J = 9.3); 8.27
(d, 2 H, ArH, J = 8.8).
SYMBOLS
Cg
Ch
con cen tration of guest, h ere con cen tration of an ion in aqueous ph ase, m ol l–1
con cen tration of h ost, h ere con cen tration of ligan d (R)-5 in organ ic ph ase,
m ol l–1
Cg – αCh
CMan d
equilibrium con cen tration of un com plexed an ion in th e aqueous ph ase
in itial con cen tration of m an delate in extraction experim en t, wh ere depen d-
en ce of extraction exten t E = [Man d]/CMan d on CMan d was evaluated, m ol l–1
equilibrium concentration of m andelate in extraction experim ent, where depend-
en ce of extraction exten t E = [Man d]/CMan d on CMan d was evaluated, m ol l–1
com plexation -in duced sh ift for approxim ation CIS ≈ ∆δ wh en large excess of
an ion is presen t (Cg >> Ch ), ppm
[Man d]
CIS
Kex
association con stan t of com plex (1:1 or 1:2) obtain ed from extraction experi-
m en t, l m ol–1
KR
KS
q
α
∆δ
association con stan t determ in ed for an ion of absolute con figuration R, l m ol–1
association con stan t determ in ed for an ion of absolute con figuration S, l m ol–1
defin ed as q = α(1 – α)–1
exten t of com plexation in th e organ ic ph ase, defin ed as α = (∆δ) CIS–1
sh ift of NMR sign al caused by addition of an ion , ppm
This work was supported by the Ministry of Education, Youth and Sports (project COST
D11/0008/98 and project MSM 2231 00001). We thank Dr J. Havlíček for measurement of 500 MHz
NMR spectra of (R)-5.
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Stibor, Holakovský, Mustafina, Lhoták:
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