Crystallographic evidence of side-arm lariat effect in the series of chiral ortho- and para-methoxyphenoxymethyl-15-crown-5 complexes with sodium perchlorate

Article abstract of DOI:10.1016/j.molstruc.2012.07.053

The single crystals of the NaClO₄ complexes with two potential lariat 15-crowns-5 having ortho- or para-methoxyphenoxymethyl side arms were investigated by X-ray analysis in racemic and enantiopure form. Only ortho-derivative demonstrates laria

Full text of DOI:10.1016/j.molstruc.2012.07.053

Journal of Molecular Structure 1032 (2013) 176–184
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Crystallographic evidence of side-arm lariat effect in the series of chiral ortho-
and para-methoxyphenoxymethyl-15-crown-5 complexes with sodium perchlorate
⇑
Alexander A. Bredikhin , Aidar T. Gubaidullin, Zemfira A. Bredikhina, Robert R. Fayzullin
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Arbuzov St. 8, Kazan 420088, Russia
h i g h l i g h t s
"
"
"
"
Four crystalline complexes of 2 chiral lariat 15-crowns-5 are prepared and investigated.
ortho-Methoxyphenoxymethyl side-arm takes part in the Na cation encapsulation.
para-Methoxyphenoxymethyl side-arm takes no part in the NaClO4 encapsulation.
First example of continuous enantiomer solid solution among crown family is found.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2012
Received in revised form 30 July 2012
Accepted 30 July 2012
Available online 16 August 2012
The single crystals of the NaClO4 complexes with two potential lariat 15-crowns-5 having ortho- or para-
methoxyphenoxymethyl side arms were investigated by X-ray analysis in racemic and enantiopure form.
Only ortho-derivative demonstrates lariat effect, i.e. the assistance of lateral fragment in cation complex-
ation. No one oxygen atom of para-substituted side arm takes part in guest encapsulation in the solid
phase. Whereas the crystals of racemic and enantiopure ortho-substituted crown complexes differ sub-
stantially from one another in packing characteristics, racemic and enantiopure complexes of para-deriv-
atives are almost isostructural. This fact indicates that the last chiral complex belong to the rare class of
continuous solid solutions of enantiomers.
Keywords:
Lariat crown ethers
Metal complexes
Single crystal X-ray analysis
Chirality driven crystallization
Guest encapsulation
Solid solution of enantiomers
Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction
1,4,7,10,13,16-hexaoxacyclooctadecane (1) with KI was investi-
gated by single crystal X-ray diffraction [4]. It was established that,
Cyclic polyethers (crowns) are one of the most popular classes of
the synthetic receptors capable of selective binding and transport of
organic and inorganic ions and molecules [1]. Some nonracemic chi-
ral crowns (usually simply named as ‘‘chiral crowns’’) show a capac-
ity for chiral recognition and predominantly bind one of the pair of
substrate enantiomers [2]. An effective molecular recognition
(chiral recognition in particular) requires that a receptor would be
capable of forming sufficiently stable complexes with substrate.
The intrinsic binding abilities of crown ethers could be enhanced
by the presence of a flexible side arm (podand fragment) with an
electron donor site(s) – the case of so called lariat ethers [1,3].
Among a variety of indirect witnesses of the side arm binding
assistance, the direct evidence of this effect for the oxygen crown
family was demonstrated only ones, when crystalline complex of
(2S,12S)-2,12-dimethyl-2,12-bis((quinolin-8-yloxy)methyl)-
alongside with six crown oxygen atoms, both heteroatom of one of
the 8-hydroxyquinoline fragments take part in the binding interac-
tions with K+ cation.
O
O
O
O
CH3
O
O
O
N
O
N
H3C
1
In the early work of Gokel et al. [5], among the simplest
representatives of lariat ethers, two 15-crowns-5, 2 and 3, having
(–CH2O–C6H4–OMe) side arms (Scheme 1) were investigated. It
was found that the ortho-methoxy derivative 2 was more effective
host for sodium cation than the para-methoxy compound 3.
Recently we have developed very effective procedure used di-
rect resolution approach for preparation of both enantiomers of
⇑
Corresponding author. Tel.: +7 843 273 45 73; fax: +7 843 273 18 72.
E-mail address: baa@iopc.ru (A.A. Bredikhin).
0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2012.07.053

A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
177
ꢁ9.4 (c 1.0, MeOH); 99.5% ee] and (S)-3-(2-methoxyphenoxy)-pro-
pane-1,2-diol [(S)-4; mp 97–99 °C; ½a D20
¼ þ9:5 (c 1.0, MeOH);
ꢀ
99.9% ee] were prepared from racemate by entrainment resolution
procedure according to previously described protocol [6].
(S)-3-(4-Methoxyphenoxy)propane-1,2-diol, (S)-6 was pre-
pared by analogy with a published procedure [8] from 4-methoxy-
phenol and (S)-3-chloropropane-1,2-diol (S)-5. Mp 79–81 °C
(n-hexane/benzene) ½a D20
¼ þ7:5 (c 0.6, EtOH); 95% ee [7].
ꢀ
The syntheses of (S)-[(2-methoxyphenoxy)methyl]-15-crown-5
[(S)-2, pale yellow oil; ½a D20
¼ ꢁ13:1 (c 1.1, CHCl3); 99.1% ee] and (S)-
ꢀ
[(4-methoxyphenoxy)methyl]-15-crown-5 [(S)-3, pale yellow oil;
Scheme 1. Methoxyphenoxymethyl substituted 15-crowns-5 and partial number-
ing scheme accepted in the text.
½
a 2D0
ꢀ
¼ ꢁ13:8 (c 6.9, CHCl3); 92.0% ee] from the corresponding diols
and tetraethyleneglycol di(p-toluenesulfonate) 7 were described in
detail earlier [7]. Racemic crowns 2 and 3 as yellowish oils were pre-
pared by analogy from rac-(2-methoxyphenoxy)propane-1,2-diol
and rac-(4-methoxyphenoxy)propane-1,2-diol, correspondingly.
General procedure for preparation of crowns 2 and 3 complexes
with NaClO4, 8 and 9. To the solution of corresponding crown ether
3-(2-methoxyphenoxy)-propane-1,2-diol 4, chiral drug guaifene-
sin [6]. Enantiopure compound 4 was used by us as the key precur-
sor for the family of nonracemic crowns. The binding and chiral
recognition ability of the so obtained hosts with respect to some
chiral ammonium salts in solutions was investigated and discussed
[7]. The advantages of crown 2 over crown 3 have been also dem-
onstrated there. Nonetheless, both these crowns are usually re-
ferred as lariats.
The initial purpose of this paper was to obtain most spectacular
evidence of the side arm participation (or nonparticipation) in the
binding with captured cation. For this reason we have prepared so-
lid complexes of crowns 2 and 3 with NaClO4 and have attempted
to establish their structure by single crystal X-ray analysis.
.
(178 mg, 0.5 mmol) in 3.5 ml of EtOAc a solution of NaClO4 H2O
(70 mg, 0.5 mmol) in 2.5 ml EtOAc was added at 40 °C. In an hour
a toluene was added to the transparent solution by drops until
the mixture becomes turbid. The mixture was kept at room temper-
ature over several days. The precipitate formed was filtered off and
washed with ether. The crude complex was purified by recrystalli-
zation from EtOAc forming white crystals of product (yield ꢂ80–
90%). These crystals were used for X-ray analysis. The properties
of the samples are as follows: complex (S)-2ꢃNaClO4, (S)-8: m.p.
110–112°C; 98.4% ee [HPLC; Chiralcel OD (0.46 ꢄ 25 cm) column;
eluent: hexane:isopropanol:diethylamine = 60:40:1; (tR = 12.7 m
(minor), tR = 21.6 m (major)]; complex rac-2ꢃNaClO4, rac-8: m.p.
87–89°C; complex (S)-3ꢃNaClO4, (S)-9: m.p. 118–119 °C (lit.[16]
m.p. 114–115 °C); 82.6% ee [HPLC; Chiralcel OD-H (0.46 ꢄ 15 cm)
column; eluent: hexane:iso propanol:diethylamine = 60:40:1;
(tR = 11.6 m (minor), tR = 14.7 m (major)]; complex rac-3ꢃNaClO4,
rac-9: m.p. 117–119 °C.
2. Experimental
2.1. Instrumentation and materials
Melting points were determined using a Boëtius apparatus and
are uncorrected. Enantiomeric purity was checked by HPLC analy-
sis performed on a Shimadzu LC-20AD system controller, and UV
monitor 275 nm was used as a detector.
2.2. X-ray analysis
Racemic guaifenesin, 3-(2-methoxyphenoxy)propane-1,2-diol,
rac-4 is commercially available (Alfa Aesar, A16827); (R)-3-(2-
The X-ray diffraction data for the crystals of crown complexes
with NaClO4 (compounds (S)-8, rac-8, (S)-9, and rac-9, see
methoxyphenoxy)-propane-1,2-diol [(R)-4; mp 97–99 °C; ½a D20
ꢀ
=
Table 1
Crystallographic data for complexes (S)-8, (S)-9, rac-9, and rac-9.
Compound formula
(S)-8 C18H28ClNaO11
rac-8 C18H28ClNaO11
(S)-9 C18H28ClNaO11
(S)-9 C18H28ClNaO11
rac-9 C18H28ClNaO11
M (g/mol)
478.84
478.84
478.84
478.84
478.84
Temperature (K)
Crystal class
Space group
Crystal size
Z, Z0
296(2)
Orthorhombic
P212121
296(2)
Orthorhombic
Pbnb
296(2)
Orthorhombic
P212121
100(2)
Orthorhombic
P212121
150(2)
Orthorhombic
Pbca
0.64 ꢄ 0.55 ꢄ 0.17 mm3 0.10 ꢄ 0.20 ꢄ 0.25 ꢄ mm3 0.04 ꢄ 0.34 ꢄ 0.52 ꢄ mm3 0.12 ꢄ 0.30 ꢄ 0.36 ꢄ mm3 0.05 ꢄ 0.20 ꢄ 0.24 ꢄ mm3
4, 1
8, 1
8, 2
8, 2
8, 1
Cell parameters
a = 12.6561(2),
b = 12.9349(2),
a = 15.401(4),
b = 15.568(4),
a = 11.4708(3),
b = 13.0205(4),
a = 11.2655(6),
b = 12.7003(7),
a = 11.247(13),
b = 12.558(15),
0
0
0
0
0
c = 14.0684(2) ÅA
2303.07(6)
c = 18.706(5) ÅA
4485(2)
c = 31.0094(9) ÅA
4631.4(2)
c = 30.9956(19) ÅA
4434.7(4)
c = 30.94(4) ÅA
4370(9)
0
V (ÅA3)
F(000)
1008
1.381
2.39
2016
1.418
2.45
2016
1.373
2.38
2016
1.434
2.48
2016
1.456
2.52
qcalc (g/cm3)
l
(cmꢁ1
)
h (°)
2.14 6 h 6 32.49
34856
7784 [R(int) = 0.0266]
293/79
3.15 6 h 6 27.94
43980
5069 [R(int) = 0.5585]
294/304
2.46 6 h 6 28.74
27013
11406 [R(int) = 0.0516]
650/183
1.31 6 h 6 31.79
22514
11617 [R(int) = 0.0453]
614/814
2.24 6 h 6 27.19
31683
4703 [R(int) = 0.7997]
281/0
Reflections measured
Independent reflections
Number of parameters/
restraints
Reflections [I > 2
r(I)]
5006
1118
4478
7455
1051
Flack parameter
0.0(3)
–
ꢁ0.10(7)
0.05(7)
–
R1/wR2 [I > 2
r
(I)]
0.0552/0.1479
0.0911/0.1743
1.013
0.457/ꢁ0.306
0.0607/0.1346
0.3209/0.2483
0.913
0.222/ꢁ0.161
0.0484/0.1005
0.1684/0.1379
0.949
0.0552/0.1070
0.0983/0.1240
1.010
0.947/ꢁ0.663
0.0789/0.1586
0.3683/0.2928
0.938
0.379/ꢁ0.332
R1/wR2 (all reflections)
Goodness-of-fit on F2
0
0.385/ꢁ0.220
qmax
/
qmin (eÅAꢁ3
)

178
A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
in the Cambridge Crystallographic Data Centre as supplementary
publication Nos. CCDC 884160–884164 respectively. Copies of
the data can be obtained free of charge upon application to the
CCDC (12 Union Road, Cambridge CB2 1EZ UK. Fax: (internat.)
+44–1223/336–033; E-mail: deposit @ccdc.cam.ac.uk).
3. Discussion
3.1. Synthesis
The synthesis of scalemic crowns (S)-2 and (S)-3 is outlined by
Scheme 2. In the first case the property of spontaneous resolution
of racemic guaifenesin 4, discovered by us earlier [6], was used as
the source of chirality. The sample of scalemic (S)-3-(4-methoxy-
phenoxy)propane-1,2-diol, (S)-6 was prepared from 4-methoxy-
phenol and (S)-3-chloropropane-1,2-diol, (S)-5.
Racemic crowns were obtained by analogy from racemic pre-
cursors. The crystalline complexes of the crowns 2 and 3 with
NaClO4 were obtained through mixing of EtOAc solutions of organ-
ic and inorganic reagents and adding toluene as the co-solvent.
3.2. Crystal structure of methoxyphenoxymethyl substituted 15-
crown-5 complexes with NaClO4
All the compounds studied have no unusual bond lengths and
bond angles. The enumeration scheme accepted here for all crown
ether derivatives is depicted in the Scheme 1. General crystallo-
graphic information is collected in Table 1.
Scheme 2. Synthetic approach to nonracemic methoxyphenoxymethyl substituted
15-crowns-5. Reagents and conditions: (i) preferential crystallization; (ii) NaOH,
ethanol/water, reflux; (iii) NaH, THF, reflux.
3.2.1. o-Methoxyphenoxymethyl substituted 15-crown-5 complexes
with NaClO4, (S)-8 and rac-8
Section 2.1) were collected on a Bruker Smart Apex II CCD diffrac-
As would be expected for the chiral nonracemic substance,
complex (S)-8 crystallizes in the Sohncke space group P212121 (Ta-
ble 1). Only one symmetry independent complex cation (S)-2ꢃNa+
and only one (slightly disordered) anion ClOꢁ4 exists in the unit cell.
Fig. 1 represents molecular structure of this independent fragment.
From Fig. 1 it is clear that the orto-methoxyderivative 2 repre-
sents a real ‘‘lariat-ether’’ where the side arm, vicinal bis-alkoxy-
substituted benzene ring, ‘‘hugs’’ the sodium cation, and together
with the crown’s basket hermetically isolates it from the contacts
with perchlorate anion (minimal Naꢃ ꢃ ꢃCl distance 6.1 Å). The
spacefill representation (Figꢁ. 1b) makes the lariat effect and the ab-
sence of direct Na+ and ClO4 contacts notably spectacular. Overall
seven oxygen atoms O1–O7 take part in the direct interaction with
the Na+ cation; the last has the usual coordination number seven.
Racemic complex rac-8 crystallizes in the centrosymmetrical
orthorhombic space group Pbnb (Table 1). The symmetry indepen-
dent part of the unit cell consists with relatively isolated complex
cation and relatively free perchlorate anion (Fig. 2), as well as its
tometer using graphite monochromated Mo Ka (0.71073 Å) radia-
tion at 296 K [(S)-8, rac-8, and (S)-9], 100 K [(S)-9] and 150 K (rac-
9). The crystal data, data collection, and the refinement parameters
are given in Table 1. The structure was solved by direct method using
SHELXS [9] program and refined by the full matrix least-squares
using SHELXL [10] programs. All non-hydrogen atoms were refined
anisotropically. The hydrogen atoms were inserted at calculated
positions and refined as riding atoms. Data collection: images were
indexed and integrated using the APEX2 data reduction package
[11]. The absolute structure of the single crystals was determined
on the basis of the Flack [12] parameter.
All calculations were performed on PC using WinGX [13] suit of
programs. Analysis of the intermolecular interactions was per-
formed using the program PLATON [14]. Mercury program package
[15] was used for figures preparation.
Crystallographic data (excluding structure factors) for the struc-
tures (S)-9, (S)-9 100 K, (S)-8, rac-8 and rac-9 have been deposited
Fig. 1. Molecular structure of enantiopure complex (S)-2ꢃNaClO4 [(S)-8]; (a) ‘‘ball-and-stick’’ stile, (b) ‘‘spacefill’’ stile.

A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
179
Fig. 2. Molecular structure of the symmetry independent fragment ((S)-enantiomer) in the crystals of rac-8; (a) ‘‘ball-and-stick’’ stile, (b) ‘‘spacefill’’ stile.
Fig. 3. Zigzag chain of the complex cations in (S)-8 crystals; C–Hꢃ ꢃ ꢃO intermolecular hydrogen bonds (red) and C–Hꢃ ꢃ ꢃ
p contacts (blue) are shown by dashed lines. Anions
ClOꢁ4 are omitted for clarity. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 4. Crystal packing of (S)-8. View along 0c axis; (a) ClO4ꢁ anions are omitted, (b) ClOꢁ4 anions are shown in ‘‘spacefill’’ stile.
homochiral analogue does. All features that are common to the
above discussed enantiopure sample are revealed here as well.
Packing indices for rac- and scal- crystals constitute 68.9% and
66.8% respectively; racemic crystals have greater density in accor-
dance with the Wallach rule. The differences between two sam-
ples, racemic and enantiomeric, are associated mainly with the
symmetry controlled packing effects.
In the absence of classical hydrogen bonds the main structure-
forming interactions in the scalemic crystals (S)-8 become hydro-
gen bonds of C–Hꢃ ꢃ ꢃO type, as well as C–Hꢃ ꢃ ꢃ
p contacts with a
participation of the electronic systems of the aromatic phenyl
fragments. Due to the C–Hꢃ ꢃ ꢃO intermolecular hydrogen bond
(IMHB) between the oxygen atom O2 of the crown fragment and
the methylene group hydrogen atom H61 belonged to symmetry

180
A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
Fig. 5. 1D Supramolecular motif in rac-8 crystals. Intermolecular H-bonds (red) and
(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
pꢃ ꢃ ꢃp
interactions (blue) are shown by dashed lines; ClOꢁ4 anions are omitted for clarity.
related molecule [d(O2ꢃ ꢃ ꢃC60) = 3.38(2) Å; d(O2ꢃ ꢃ ꢃH610) = 2.69 Å;
\(O2ꢃ ꢃ ꢃH610–C60) = 128.7°; (1/2 + x, 3/2 ꢁ y, 1 ꢁ z)] the zigzag
‘‘head-to-tail’’ chain is formed along the 21 screw axis in the 0a
At the same time the opposite side of the aromatic fragment
contact with the H220 hydrogen
takes part in the one else CHꢃ ꢃ ꢃ
p
atom belonged to the molecule possessed by neighboring zigzag
(H220ꢃ ꢃ ꢃCg distance is equal to 3.00 Å, symmetry operation ꢁ3/
2 ꢁ x, 1 – y, ꢁ1/2 + z). All these interactions in aggregate lead to
the 3D supramolecular structure were the binding along 0a axis
is realized due to IMHB C–Hꢃ ꢃ ꢃO, and along 0b and 0c axes due to
direction (Fig. 3). The C–Hꢃ ꢃ ꢃ
p contact between the phenyl moiety
electronic system and the hydrogen atom H42 of the nearest mol-
ecule acts in the same direction; the distance H42ꢃ ꢃ ꢃCg (center of
gravity of the aromatics) is equal to 2.68 Å, symmetry operation
1/2 + x, 3/2 ꢁ y, 1 ꢁ z (Fig. 3).
C–Hꢃ ꢃ ꢃ
p contacts. The so formed packing has a lace-like character
Fig. 6. Molecular packing in the rac-8 crystals. View along 0a (a and b) and 0b (c and d) axes; ClOꢁ4 anions are omitted (a and c) or shown in ‘‘spacefill’’ stile (b and d).

A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
181
The main structural unit in the rac-8 crystals may be considered
as a centrosymmetrical dimer of two enantiomeric complex cations
bound together by the type of ‘‘head-to-head’’ with the aid of pair of
intermolecular CHꢃ ꢃ ꢃO hydrogen bonds between O3 oxygen atoms
belonged to the adjacent crown-fragments and the appropriate
H220 atoms of methylene groups of the same fragments. This inter-
action could be characterized as follows: d(O3ꢃ ꢃ ꢃH220) = 2.68 Å,
\(C20–H22’ꢃ ꢃ ꢃO3) = 165°, d(O3ꢃ ꢃ ꢃC20) = 3.625(6)Å, (2 ꢁ x, 1 ꢁ y, ꢁz).
Relative position of these dimers is favorable for dual
p p contacts
ꢃ ꢃ ꢃ
between electron systems of phenyl substituents belonged to adja-
cent molecules related by center of symmetry. For this interaction
d(Cgꢃ ꢃ ꢃCg0) = 3.86 Å, dihedral angle between aromatic planes is
equal to 0°, and the shortest distance between these Arꢃ ꢃ ꢃAr planes
is equal to 3.42 Å. The interlacing of the dual C–Hꢃ ꢃ ꢃO IMHB and
p p contacts forms 1D molecular chains along crystallographic
ꢃ ꢃ ꢃ
0a axis (Fig. 5). Thanks to central symmetry, these 1D chains are
dense enough, and owing to peripheral dispersion interactions they
associate into dense layers parallel to 0ab plain (Fig. 6a and c). We
believe that the dense nature of the primary (chain) and secondary
(layer) crystal-forming motifs is the reason for moderately high
packing index of rac-8.
Fig. 7. Structure of two symmetry independent A and B molecules in (S)-9 crystals;
296 K.
The layers have almost no contacts between one another form-
ing interlayer cavities which channel-like character is particularly
evident from Fig. 6a. Within the cavities slightly disordered ClO4ꢁ
anions stacks are located; the shortest Clꢃ ꢃ ꢃCl distances are equal
to 6.43 Å (in 0a direction), 7.84 Å (0b direction), and 9.51 Å (0c
direction).
3.2.2. p-Methoxyphenoxymethyl substituted 15-crown-5 complexes
with NaClO4, (S)-9 and rac-9
The structure of the complex of (S)-[(4-methoxyphen-
oxy)methyl]-15-crown-5 with NaClO4, (S)-9, was investigated by
X-ray method earlier [16]. Despite the fact that the sample under
investigations was described by the authors as enantiopure, the
crystal structure was solved in the centrosymmetric orthorhombic
space group Pbca [16]. This gives a contradiction which could be
interpreted by two ways. First interpretation is that racemic sam-
ple was erroneously used instead of enantiomeric one for single
crystal X-ray analysis. Second explanation is that this case provides
another example of the ‘‘dangers inherent in the conventional wis-
dom that if a structure can be refined satisfactorily in both centro-
symmetric and non-centrosymmetric space groups, the former
should always be chosen’’ [17]. In the cited paper George Sheldrick
also writes that despite apparently acceptable intensity statistics
and R factors, the choice of the centrosymmetric space group leads
to the serious chemical error that the unit cell contains the race-
mate rather than two chiral molecules. In both cases the published
data for (S)-9 are erroneous. So we have undertaken the attempt to
Fig. 8. Thermal ellipsoids (50% probability level) for symmetry independent A and
B molecules in (S)-9 crystal; 100 K. The statistically disordered A molecule is
represented by most populated subsite; hydrogen atoms are omitted.
with channels penetrating the crystal space (Fig. 4a); within these
channels ClOꢁ4 anions stacks are located, with the shortest Clꢃ ꢃ ꢃCl
distances are in the range 7.30–7.98 Å (Fig. 4b). Apparently, these
peculiarities are the reason for the above mentioned scalemic crys-
tals ‘‘looseness’’.
Table 2
Parameters of the intermolecular H-bonds and C–Hꢃꢃꢃ
p interactions for complexes (S)-9 (100 K) and rac-9 in crystals.
D–Hꢃ ꢃ ꢃA
D–H (Å)
Hꢃ ꢃ ꢃA (Å)
Dꢃ ꢃ ꢃA (Å)
\ DHA (o)
Symmetry operation
(S)-9 (100 K)
C6B–H62Bꢃ ꢃ ꢃO33B
C16A–H16Aꢃ ꢃ ꢃO31A
C18A–H181ꢃ ꢃ ꢃO32B
C18B–H184ꢃ ꢃ ꢃO32A
0.99
0.95
0.98
0.98
2.59
2.56
2.52
2.55
3.320(4)
3.514(4)
3.437(4)
3.488(4)
130
178
156
161
Xꢃ ꢃ ꢃCg
3.556(3)
3.60(2)
1 – x, ꢁ1/2 + y, 1/2 ꢁ z
1/2 + x, 1/2 ꢁ y, ꢁz
[ꢁ1/2 + x, 3/2 ꢁ y, ꢁz
1/2 + x, 3/2 ꢁ y, ꢁz
Symmetry operation
–
Hꢃ ꢃ ꢃCg (Å)
\C–Hꢃ ꢃ ꢃCg (o)
C1B–H1B ? CgA
C2A–H2A2 ? CgB
2.65
152
147
2.73
x, ꢁ1 + y, z
rac-9
C6–H61ꢃ ꢃ ꢃO33
0.99
0.98
2.54
2.51
3.281(14)
3.447(12)
131
160
1 ꢁ x, ꢁ1/2 + y, 1/2 ꢁ z
1 ꢁ x, 1 ꢁ y, ꢁz
C18–H181ꢃ ꢃ ꢃO32
Hꢃ ꢃ ꢃCg (Å)
\C–Hꢃ ꢃ ꢃCg (o)
155
Xꢃ ꢃ ꢃCg
Symmetry operation
3/2 ꢁ x, ꢁ1/2 + y, z
C1–H1 ? Cg
2.63
3.56(1)

182
A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
Fig. 9. Crystal packing for (S)-9. Corrugated layers, view along 0a axis; top view on the layer (along 0b axis).
side arm of the crown 3 takes no part in the guest binding. Within
the complex (S)-9 the coordination number of sodium cation re-
mains equal to 7, but only 5 coordination positions are occupied
by basket oxygen atoms. Two other positions are occupied by oxy-
gen atoms of ClO4 moiety. Thus, the guest is, in this instance, not a
sodium cation, but a neutral NaClO4 molecule.
The independent (S)-9 molecules have a slightly different con-
formation of the para-methoxyphenoxymethyl fragments. For the
sequence O1C1C11O6C12C13 (see Scheme 1 for numbering) it
could be characterized by dihedral angles 155°, 167°, and 165°
for A molecule and 174°, 178°, and 177° for B molecule. The posi-
tion of B molecule as a unit and of the para-methoxyphenoxymeth-
yl fragment of A molecule within the crystal lattice are accurately
fixed. At the same time the analysis of thermal anisotropic param-
eters reveals that the position of crown-fragment of the A molecule
in the crystal is disordered in two subsites with the same relative
populations. This disordering can be both dynamic and statistical
in nature. As the next step, we have performed an X-ray diffraction
experiment at low temperature (100 K), which allows, to a certain
degree, to exclude from consideration the dynamic nature of the
disorder.
Fig. 10. Structure of symmetry independent molecule in rac-9 crystals.
prepare both enantiopure and racemic crystals of complex 9 in or-
der to investigate them by single crystal X-ray diffraction.
Room temperature experiment revealed that complex (S)-9
forms orthorhombic crystals (space group P212121) with two sym-
metry independent molecules A and B in the unit cell. Molecular
structure of the complex (S)-9 (Fig. 7) differs dramatically from
the above (S)-8 and rac-8 in that the para-methoxyphenoxymethyl
Low-temperature experimental results allow inclining to the
version of the statistical nature of the disorder. The experiment
showed again that the position of the crown-fragment of the
independent molecule A in the crystal are disordered over two

A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
183
Fig. 11. Fragment of crystal packing in rac-9 crystals; view along 0a axis.
Fig. 12. The relative position of two symmetry independent molecules in the crystals of enantiopure sample (S)-9 (a) and of two molecules, related by glade plane (1/2 ꢁ [, 1/
2 + y, z) in the crystals of racemic sample rac-9 (b).
positions, although the relative populations now are calculated to
be 0.79 and 0.21. The positions of the independent molecule B, as
well as the para-methoxyphenoxymethyl fragment of the disor-
dered molecule A, proved to be very stable, as evidenced by the
temperature ellipsoid parameters of the atoms (Fig. 8).
time their mutual arrangement allows one to identify the perpen-
dicular zones, mainly consisting of hydrophilic (crown fragments
containing) or hydrophobic (aromatic fragments containing) com-
ponents (Fig. 9a). In contrast to the complex 8, the crystal lattice of
complex 9 contains no significant
pꢃ ꢃ ꢃp type contacts.
As the temperature of X-ray experiment decreases, the geome-
try of the molecules in the crystal is changed insignificantly. With-
in the unit cell to the greatest extent vary (diminish) the
parameters a (from 11.4708(3) Å to 11.2655(6) Å) and b (from
13.0205(4) Å to 12.7003(7) Å). Note that in these directions the
mutual packing of crown-fragments of molecules is realized. Anal-
ysis of the intermolecular interactions in (S)-9 crystals is indicative
of the presence of intermolecular hydrogen C–Hꢃ ꢃ ꢃO bonds and C–
Racemic complex of NaClO4 with crown ether 3 having para-
disubstituted acyclic moiety, rac-9, forms orthorhombic crystals
(space group Pbca) with one independent molecule in the unit cell
(Fig. 10); para-methoxyphenoxymetyl fragment is nearly planar,
torsion angles C1C11O6C12, C11O6C12C13 and C14C15O7C18
are equal to 171°, 12°, and 178° respectively. As in the enantiopure
crystals (S)-9, the lateral fragment is not involved in coordination
with the sodium atom; two free coordination positions are occu-
pied by oxygen atoms of the ClO4ꢁ anion. Thus, it can be argued that
the crown ether 3, at least in the solid state, is not a lariat ether,
neither in racemic nor in enantiopure form.
Hꢃ ꢃ ꢃ
p binding contacts. Looking ahead, we note that the types of
interactions and their parameters are remarkably close to that of
rac-9 crystals. All of the identified interactions are summarized
for convenience in the Table 2. The mutual action of C–Hꢃ ꢃ ꢃO H–
Comparison of the data of Table 1 indicates a very close unit cell
parameters for the enantiopure and racemic 9 samples. Kitajgorod-
skij packing indices are almost equal for enantiomeric (70.2% at
100 K) and racemic (71.0%) complexes 9. Furthermore, it follows
bonds and C–Hꢃ ꢃ ꢃ
p binding contacts leads to formation of 3D
supramolecular structure characterized by dense arrangement of
corrugated layers, one of which is shown in Fig. 9b. At the same

184
A.A. Bredikhin et al. / Journal of Molecular Structure 1032 (2013) 176–184
from Table 2 that the parameters of the intermolecular interac-
tions, responsible for supramolecular organization of the crystals
(S)-9 and rac-9, are also close. Fig. 11 shows a fragment of molec-
ular packing in rac-9 crystals. We see here the same corrugated
layers with alternating hydrophilic and hydrophobic zones, as in
Fig. 9a.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.molstruc.2012.
07.053. These data include MOL files and InChiKeys of the most
important compounds described in this article.
All these facts indicate the isostructural crystalline organization
of (S)-9 and rac-9. However, it should be remembered that while
the molecules of only one configuration are involved in the con-
struction of homochiral crystals, pairs of molecules of opposite
configuration by definition are involved in the construction of race-
mic crystals. This, in turn, means that the isostructurality can be
realized in the presence within both unit cells of a site, «enclosing»
a molecule of arbitrary configuration. For the case under investiga-
tion these sites are depicted in Fig. 12. The R-molecule, symmetry
related with S-molecule in the rac-9 crystal unit cell (Fig. 12b),
occupies just the same position as one of the symmetry indepen-
dent S-molecules occupies in the unit cell of (S)-9 crystal
(Fig. 12a). In this case, all existing in both crystals metric relations
remain virtually unchanged.
In the case of chiral compounds, the situation like this is typical
for solid solutions [18]. It seems that complex 9 really belongs to
the rare class of continuous solid solutions. We could add two
other arguments. Firstly, both (S)-9 and rac-9 have very similar
melting temperatures, 118–119 °C and 117–119 °C. Secondly, 3-
(4-methoxyphenoxy)-propane-1,2-diol, synthetic precursor of
crowns 3, forms an ideal continuous solid solution of enantiomers
in full concentration region [19].
References
[1] J.W. Steed, J.L. Atwood, Supramolecular Chemistry, second ed., Wiley, 2009.
[2] (a) J.F. Stoddart, Top. Stereochem. 17 (1988) 207;
(b) M.-Z. Gao, Y.-O. Yang, Z.-L. Xu, Chin. J. Org. Chem. 21 (2001) 477;
(c) M.H. Hyun, J. Sep. Sci. 26 (2003) 242;
(d) M. Lämmerhofer, J. Chromatogr. A 1217 (2010) 814.
[3] (a) G.W. Gokel, O.F. Schall, Lariat ethers, in: G.W. Gokel (Ed.), Comprehensive
Supramolecular Chemistry, Pergamon, New York, 1996, p. 97;
(b) A.H.M. Elwahy, A.A. Abbas, J. Heterocycl. Chem. 45 (2008) 1;
(c) A.A. Abbas, A.H.M. Elwahy, J. Heterocycl. Chem. 46 (2009) 1035.
[4] M. Muraoka, A. Ueda, W. Zhang, T. Kida, Y. Nakatsuji, I. Ikeda, N. Kanehisa, Y.
Kai, Tetrahedron Lett. 39 (1998) 9493.
[5] G.W. Gokel, D.M. Dishong, C.J. Diamond, Chem. Commun. (1980) 1053.
[6] Z.A. Bredikhina, V.G. Novikova, D.V. Zakharychev, A.A. Bredikhin, Tetrahedron:
Asymmetry 17 (2006) 3015.
[7] Z.A. Bredikhina, R.M. Eliseenkova, R.R. Fayzullin, V.G. Novikova, S.V.
Kharlamov, D.R. Sharafutdinova, Sh.K. Latypov, A.A. Bredikhin, ARKIVOC (x)
(2011) 16.
[8] A.A. Bredikhin, Z.A. Bredikhina, V.G. Novikova, A.V. Pashagin, D.V. Zakharychev,
A.T. Gubaidullin, Chirality 20 (2008) 1092.
[9] G.M. Sheldrick, SHELXS 97 Program for Solution of Crystal Structure, University
of Goettingen, Germany, 1997.
[10] G.M. Sheldrick, SHELXL97
a Computer Program for Crystal Structure
Determination, University of Gottingen, 1997.
[11] APEX2 (Version 2.1), SAINTPlus. Data Reduction and Correction Program
(Version 7.31A), Bruker Advanced X-ray Solutions, Bruker AXS Inc., Madison,
Wisconsin, USA, 2006.
[12] (a) H.D. Flack, Acta Crystallogr. A39 (1983) 876;
(b) H.D. Flack, G. Bernardinelli, J. Appl. Crystallogr. 33 (2000) 1143.
[13] L.J. Farrugia, J. Appl. Crystallogr. 32 (1999) 837.
4. Conclusion
[14] A.L. Spek, J. Appl. Crystallogr. 36 (2003) 7.
[15] C.F. Macrae, P.R. Edgington, P. McCabe, E. Pidcock, G.P. Shields, R. Taylor, M.
Towler, J. van de Streek, J. Appl. Crystallogr. 39 (2006) 453.
The single crystal X-ray diffraction investigations tell us that
within the family of 15-crowns-5 possessing metoxyphenoxym-
ethyl (–CH2O–C6H4–OMe) side arms only ortho-derivative
2
˘
[16] N. Dogan, S. Özbey, M. Karakaplan, T. Aral, J. Chem. Crystallogr. 38 (2008) 943.
[17] M. Walker, E. Pohl, R. Herbst-Irmer, M. Gerlitz, J. Rohr, G.M. Sheldrick, Acta
Crystallogr. B55 (1999) 607.
demonstrates the assistance of lateral fragment in cation complex-
ation (lariat effect) in solid state. No one oxygen atom of para-
substituted side arm in crown 3 takes part in cation encapsulation
in the solid phase. The effects were demonstrated for both homo-
chiral and racemic samples. The crystals of racemic and enantio-
[18] (a) B. Chion, J. Lajzerowicz, D. Bordeaux, A. Collet, J. Jacques, J. Phys. Chem. 82
(1978) 2682;
(b) F.G. Voght, R.C.B. Copley, R.L. Mueller, G.P. Spoors, T.N. Cacchio, R.A.
Carlton, L.M. Katrincic, J.M. Kennady, S. Parsons, O.V. Chetina, Cryst. Growth
Des. 10 (2010) 2713;
(c) H. Lopez de Diego, A.D. Bond, R.J. Dancer, Chirality 23 (2011) 408;
(d) A.A. Bredikhin, Z.A. Bredikhina, D.V. Zakharychev, A.T. Gubaidullin, R.R.
Fayzullin, CrystEngComm. 14 (2012) 648.
pure ‘‘ortho-crowns’’
2
complexes with NaClO4 differ
substantially from one another in packing characteristics. At the
same time racemic and enantiopure complexes of ‘‘para-crowns’’
3 are almost isostructural. We believe that these chiral complexes
belong to the rare class of continuous solid solutions of
enantiomers.
[19] A.A. Bredikhin, Z.A. Bredikhina, D.V. Zakharychev, Mendeleev Commun. 22
(2012) 171.