Inclusion ability and selectivity of ethylenediamine derivatives for pyridine in the presence of methylpyridine isomers

Article abstract of DOI:10.1007/s10847-019-00966-y

The inclusion behaviour of compounds N,N′-bis(9-cyclohexyl-9-xanthenyl)ethylenediamine (OED) and N,N′-bis(9-cyclohexyl-9-thioxanthenyl)ethylenediamine (SED) was assessed in the presence of pyridine (PYR) and its three methylpyridine isomers (2MP, 3MP and 4MP). PYR, 3MP and 4MP were each enclathrated by OED when it was recrystallized independently from each guest solvent, but failed to include 2MP. The thio host derivative, SED, was less efficient, forming a complex only with PYR. When these guests were mixed in equimolar amounts and each host recrystallized from the mixture, OED constantly displayed a significantly enhanced preference for 4MP (near-complete in many instances), while complexation failed under these circumstances for SED, even when PYR was present in the guest mixture (despite PYR having been included in the single solvent experiment). A selectivity order of 4MP (92.8%) ? PYR (6.0%) > 3MP (0.9%) > 2MP (0.3%) was noted for OED when it was recrystallized from the equimolar quaternary mixed solvent system. The selectivity of OED towards 4MP was investigated using single crystal diffraction (SCXRD) and thermal (TA) analyses: interestingly, only 4MP experienced a strong classical hydrogen bond with OED, in direct relation to the enhanced selectivity of OED for 4MP while, additionally, this complex displayed an increased thermal stability relative to the other two complexes with OED.

Full text of DOI:10.1007/s10847-019-00966-y

Journal of Inclusion Phenomena and Macrocyclic Chemistry
https://doi.org/10.1007/s10847-019-00966-y
ORIGINAL ARTICLE
Inclusion ability and selectivity of ethylenediamine derivatives
for pyridine in the presence of methylpyridine isomers
Ulrich Senekal1 · Benita Barton1 · Eric C. Hosten1
Received: 16 September 2019 / Accepted: 21 November 2019
© Springer Nature B.V. 2019
Abstract
The inclusion behaviour of compounds N,N′-bis(9-cyclohexyl-9-xanthenyl)ethylenediamine (OED) and N,N′-bis(9-
cyclohexyl-9-thioxanthenyl)ethylenediamine (SED) was assessed in the presence of pyridine (PYR) and its three methyl-
pyridine isomers (2MP, 3MP and 4MP). PYR, 3MP and 4MP were each enclathrated by OED when it was recrystallized
independently from each guest solvent, but failed to include 2MP. The thio host derivative, SED, was less efcient, forming a
complex only with PYR. When these guests were mixed in equimolar amounts and each host recrystallized from the mixture,
OED constantly displayed a signifcantly enhanced preference for 4MP (near-complete in many instances), while complexa-
tion failed under these circumstances for SED, even when PYR was present in the guest mixture (despite PYR having been
included in the single solvent experiment). A selectivity order of 4MP (92.8%)≫PYR (6.0%)>3MP (0.9%)>2MP (0.3%)
was noted for OED when it was recrystallized from the equimolar quaternary mixed solvent system. The selectivity of OED
towards 4MP was investigated using single crystal difraction (SCXRD) and thermal (TA) analyses: interestingly, only 4MP
experienced a strong classical hydrogen bond with OED, in direct relation to the enhanced selectivity of OED for 4MP while,
additionally, this complex displayed an increased thermal stability relative to the other two complexes with OED.
Keywords Host–guest chemistry · Supramolecular chemistry · Xanthenyl · Pyridine · Methylpyridine
Introduction
whether they possess inter- (cavitands) or extra-molecular
cavities (clathrands) [3].
Host–guest chemistry forms part of the larger supramolecu-
lar chemistry feld that can simply be defned as the com-
plexation of two or more diferent compounds by means of
non-covalent interactions. The aforementioned molecular
compounds comprise host (H) molecules that crystallize
and, in so doing, form cavities or channels in which suitable
guest (G) compounds are trapped. Non-covalent forces such
as hydrogen bonding, ion pairing, π‒π, CH‒π and van der
Waals interactions are generally the forces responsible for
this entrapment of the guest species [1–3]. The host com-
pounds may be subdivided into two major groups based on
Host–guest chemistry fnds various applications in the
chemical, biological and pharmaceutical felds such as the
separation of enantiomers and other isomeric mixtures [3],
modification of stationary phases for chromatography-
assisted separations [4], storage of toxic ions, molecules and
gases [3, 5], and increase in the water solubility, stability
and bioavailability of drugs [2]. Some host compounds also
display bioactivity, and an example is the calixarenes [6].
Pyridine (PYR) and the methylpyridine isomers (MPs,
picolines, Scheme 1) are some of the main components
found in the light oil fraction (up to a boiling point of
180 °C) of coal tar and may also be obtained through high
temperature vapour phase processes involving acetaldehyde,
ammonia and formaldehyde in the presence of a catalyst [7,
8]. These compounds are employed in the preparation of
polyamides, herbicides, dyes, insecticides, resins and phar-
maceuticals [9]. The challenge associated with the separa-
tion of the MP isomers from PYR (b.p. 116 °C) or from
one another is as a result of their similar physical properties
(boiling points, 2MP 129 °C, 3MP 144 °C, 4MP 145 °C),
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10847-019-00966-y) contains
supplementary material, which is available to authorized users.
* Ulrich Senekal
s214099601@mandela.ac.za
1
Department of Chemistry, Nelson Mandela University, PO
Box 77000, Port Elizabeth 6031, South Africa
Vol.:(0123456789)
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Journal of Inclusion Phenomena and Macrocyclic Chemistry
PYR
2MP
3MP
4MP
OED: X = O
SED: X = S
Scheme 1 Molecular structures of host compounds N,N′-bis(9-
cyclohexyl-9-xanthenyl)ethylenediamine (OED) and N,N′-bis(9-
cyclohexyl-9-thioxanthenyl)ethylenediamine (SED), and guests pyri-
dine (PYR), 2-methylpyridine (2MP), 3-methylpyridine (3MP) and
4-methylpyridine (4MP)
and so requires multiple fractional distillations or their syn-
theses from alternative precursors, which ensures that less
conventional separation strategies become more alluring [8].
Researchers only recently considered the separation of
PYR and its MP isomers through principles of host–guest
chemistry. As examples, Bacsa et al. explored the wheel-
and-axle type host, 1,1,6,6-tetraphenylhexa-2,4-diyne-
1,6-diol, and found it to possess clathration ability in the
presence of each of PYR, 3MP and 4MP. PYR and 4MP
were each shown to occupy channels in the host crystal,
while two of the 3MP guests occupied a single cage. Addi-
tionally, this host displayed selectivity for 4MP when in the
presence of 4MP/PYR mixtures, and (host)O‒H···N(guest)
hydrogen bonds were responsible for the stabilization of the
complexes [10]. Nassimbeni et al. considered a host frst
designed and synthesized by Weber et al., 9,9′-(ethyne-1,2-
diyl)bis(fuoren-9-ol), containing two rigid hydroxyfuorenyl
moieties connected by a spacer unit, for this purpose [11,
12]. This host formed inclusion compounds with all the MP
guests, but distinctly favoured 4MP over the others. More
recently, (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-
tetraol (TETROL) was assessed for its possible application in
the separation of these guest types [13]. This host compound
possesses a rigid butane backbone, which adopts an anti
conformation, as well as hydrogen bonding capabilities due
to the presence of the four hydroxyl groups. Interestingly,
TETROL displayed a similar tendency to form complexes
with these solvents as 1,1,6,6-tetraphenylhexa-2,4-diyne-
1,6-diol, and a selectivity order of 4MP>3MP>PYR>2MP
was noted. The behaviour of racemic and optically pure
α,α,α′,α′-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5-
dimethanol (TADDOL), synthesized from the appropriate
tartaric acid, has also been reported, and both hosts possess
the ability to clathrate all four of these guests types [14].
Both also displayed a preference for 3MP (75% and 69%,
respectively) when each was recrystallized from an equi-
molar mixture of the four solvents. In order to attempt to
improve on these selectivities, host compound N,N′-bis(9-
phenyl-9-thioxanthenyl)ethylenediamine was employed in
these experiments, but it only contained 47% of 3MP when
recrystallized from the quaternary guest mixture [15].
In the present work, modifed ethylenediamine-linked
xanthenyl and thioxanthenyl host systems, N,N’-bis(9-
cyclohexyl-9-xanthenyl)ethylenediamine (OED) and N,N′-
bis(9-cyclohexyl-9-thioxanthenyl)ethylenediamine (SED),
were employed in an attempt to improve on the very ordinary
host selectivities in the presence of the title guest compounds
reported before (Scheme 1), with exceptional fndings. It has
very recently been noted that these host compounds display
preferential behaviour in the presence of xylenes and ethylb-
enzene [16], but their host ability in the presence of PYR
and the MPs has not been reported to date. The successfully-
formed complexes were analyzed by means of single crystal
X-ray difraction (SCXRD) and thermal analyses (TA) in
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
order to understand better the reasons for any preferential
behaviour displayed by these host compounds.
Single solvent experiments
Table 1 summarizes the results of the experiments where
hosts OED and SED were individually recrystallized from
Results and discussion
Table 1 The H:G ratios of the
Guest
OED
1:1
–
2:1
1:2
SED
1:1
Synthesis of OED and SED
complexes formed with OED
and SED
PYR
2MP
3MP
4MP
b
b
OED and SED were prepared very simply by considering a
previous report [16]. A Grignard reaction was performed on
xanthone 1 and thioxanthone 2 using cyclohexylmagnesium
bromide followed by an acid workup to yield the respective
alcohols 3 and 4 (Scheme 2). These were treated with per-
chloric acid to aford perchlorate salts 5 and 6 which were, in
turn, added to ethylenediamine to aford the desired crystal-
line host compounds OED and SED, respectively.
–
–
b
b
–
a1H-NMR spectroscopy was
used to determine the host:guest
(H:G) ratios, with CDCl3 as sol-
vent
bNo inclusion occurred
1)
2)
3: X = O
4: X = S
1: X = O
2: X = S
OED: X = O
SED: X = S
5: X = O
6: X = S
Scheme 2 Synthetic route towards hosts OED and SED
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
Table 2 Results of competition experiments for host OED when
each of the PYR and MP guest compounds. The results are
strikingly contrasting in that OED formed inclusion com-
pounds with each of PYR, 3- and 4-MP, but did not clath-
rate 2-MP; host:guest (H:G) ratios varied (1:1, 2:1 and 1:2,
respectively). SED, on the other hand, failed to form any
complexes with each of the MPs and only clathrated PYR
(H:G ratio 1:1).
recrystallized from equimolar mixtures of PYR, 2MP, 3MP and 4 MP
PYR
2MP
3MP
4MP
Guest ratios
(% e.s.d.s)a
Overall
H:G
ratio
X
X
X
X
66.8:33.2
1:1
1:1
1:2
2:1
1:2
1:2
(1.4)
X
69.1:30.9
(0.3)
Competition experiments using equimolar guest
mixtures
X
23.1:76.9
(1.6)
X
X
X
33.4:66.6
Equimolar competition experiments were employed in order
to observe whether hosts OED and SED would display selec-
tivity in the presence of mixtures of these guests. Surpris-
ingly, binary, ternary and quaternary guest competition
experiments with SED as the host resulted in only apohost
crystallizing out, and none of these guests were included in
this way. This was the case even where PYR was present (the
only guest compound to form a complex with SED in the
single solvent experiments). The obtained data are summa-
rized in Table 2, and the preferred guest is indicated in bold
italic text with percentage estimated standard deviations (%
e.s.d.s) provided in parentheses.
(0.5)
X
X
3.2:96.8
(0.7)
X
X
5.2:94.8
(0.4)
b
b
X
X
X
X
–
‒
X
X
X
X
20.3:5.0:74.7
1:2
1:2
1:2
1:2
(2.9)(1.0)(3.9)
X
X
X
X
13.8:2.8:83.4
(0.2)(0.7)(0.5)
X
X
1.6:1.9:96.5
(0.1)(0.0)(0.1)
X
6.0:0.3:0.9:92.8
OED displayed a signifcant preference for 4MP (76.9%,
96.8% and 94.8%, respectively) when it was recrystallized
from PYR/4MP, 2MP/4MP and 3MP/4MP binary mix-
tures, while PYR/2MP and PYR/3MP experiments led to
the favourable complexation of PYR (66.8% and 69.1%,
respectively) (Table 2). In the absence of PYR and 4MP
(2MP/3MP), 3MP was the favoured guest (66.6%), and by
considering only these binary experiments, a host selectiv-
ity order of 4MP>PYR>3MP>2MP may be established.
The ternary equimolar experiment using 2MP/3MP/4MP
showed that 4MP was, once more, favoured, with 96.5%
of this guest being present in the mixed complex; only
small amounts of the other two guests were present [3MP
(1.9%) and 2MP (1.6%)]. A PYR/2MP/3MP mixture where
two of the least preferred guests were present (2MP and
3MP) failed to form a complex, while the PYR/2MP/4MP
and PYR/3MP/4MP, in which neither 2MP nor 3MP were
present simultaneously, did indeed form inclusion com-
pounds [PYR (20.3%), 2MP (5.0%), 4MP (74.7%) and PYR
(13.8%), 3MP (2.8%), 4MP (83.4%)]. When all four guests
were mixed in equimolar proportions and the host recrys-
tallized from this mixture, the resulting complex contained
92.8% 4MP, which is a remarkable improvement on previous
reports. The selectivity order of host OED was therefore
4MP (92.8%)≫PYR (6.0%)>3MP (0.9%)>2MP (0.3%) for
these guests, in direct correlation with observations made
from the binary experiments. Notable is the observation that
successfully-formed mixed complexes containing 4MP (the
preferred guest) constantly adopted an overall H:G ratio that
(0.6)(0.0)(0.1)(0.7)
Guest:guest and overall H:G ratios were determined using GC–MS
and 1H-NMR spectroscopy, respectively
aThe % e.s.d.s obtained from triplicate data sets are displayed in
parentheses
bCrystals contained no guest solvent/s
corresponded with that of the OED·4MP complex from the
single solvent experiment (Table 1, 1:2).
Competition experiments using varied guest
concentration mixtures
The host behaviour of OED was also investigated when
it was recrystallized from binary guest 1:guest 2 (G1:G2)
mixtures with varying amounts of each guest present (from
approximately 20:80 to 80:20 G1:G2 mol%). The selectivity
profles so-obtained are presented in Fig. 1a‒f, where the
black dotted line represents an unselective host compound
(K = 1) for comparative purposes. The average selectiv-
ity coefcient (K) was only calculated for the PYR/2MP
mixture, whereas the highest selectivity coefcients for the
remaining binary guest mixtures were calculated and pro-
vided herein.
Figure 1a represents the selectivity profle of host OED
when recrystallized from various concentrations of PYR and
2MP in binary mixtures. At low concentrations of PYR in
the mother liquor (<42%), OED displayed only a slight pref-
erence for this guest relative to 2MP: a complex with 24.6%
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
(a)
(b)
100
100
80
60
40
20
0
80
60
40
20
0
0
20
40
60
80
100
0
20
40
60
80
100
XPYR
XPYR
(d)
(c)
100
80
60
40
20
0
100
80
60
40
20
0
0
20
40
60
80
100
0
20
40
60
80
100
X4MP
X3MP
(e)
100
80
60
40
20
0
100
80
60
40
20
0
(f)
0
20
40
60
80
100
0
20
40
60
80
100
X4MP
X4MP
Fig. 1 OED selectivity profles for the a PYR/2MP, b PYR/3MP, c PYR/4MP, d 2MP/3MP, e 2MP/4MP and f 3MP/4MP mixtures
PYR and 75.4% 2MP was isolated from a 16.0% PYR and
84.0% 2MP solution. However, as the concentration of PYR
in the mother liquor increased, so did the presence of this
guest in the crystal: when the mother liquor comprised 47.4
and 69.1% PYR, the amount of this guest in the resultant
complexes was found to be 77.4% and 88.7%, respectively.
It is clear that OED was selective for PYR over the entire
concentration range evaluated (the averaged K value was
calculated to be 2.4).
mother liquors, and the most signifcant selection towards
this guest was 98.5%, and was obtained from a 69.5:30.5
PYR:3MP solution (K=28.3).
The selectivity profle of OED for the PYR/4MP competi-
tion experiment (Fig. 1c) also showed that the selectivity of
this host depended on the concentration of the guests. PYR
was initially preferred by OED (95.8%) when the mother
liquor contained 30.1% of 4MP and 69.9% of PYR. The host
preference then switched from PYR to 4MP when approxi-
mately 40% of 4MP was present in the mother liquor: a solu-
tion comprising 60.9% 4MP aforded a mixed crystalline
complex with 88.7% of 4MP present (K=5.0).
In contrast, the selectivity of OED when recrystallized
from PYR/3MP mixtures was guest concentration depend-
ent (Fig. 1b): a low concentration of PYR (13.6%) in the
mother liquor aforded a mixed complex with a signifcant
amount of 3MP (96.3%). The selectivity of the host was then
altered when the PYR concentration in the mother liquor
was approximately 23%: from this point on, the amount of
PYR in the resultant complexes surpassed that present in the
From 2MP/3MP mixtures, OED remained rather unse-
lective for either guest when low concentrations of 3MP
(<43%) were present (Fig. 1d). The selectivity for 3MP was,
however, enhanced as its concentration in the mother liquor
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
Fig. 2 Unit cells of a
OED·PYR, b 2OED·3MP, c
OED·2(4MP) and d SED·PYR;
host compounds are represented
in a ball-and-stick style while
the guests are shown in space-
fll representation
further increased: a mother liquor of 81.0% 3MP aforded
crystals containing 89.6% 3MP and 10.4% 2MP (K=2.0).
The selectivity profles obtained from both the 2MP/4MP
(Fig. 1e) and 3MP/4MP (Fig. 1f) mixtures showed that
2MP (83.2%) and 3MP (94.4%) were present in increased
amounts in the formed complexes when the mother liquors
contained high concentrations of 2MP (78.5%) and 3MP
(81.2%), respectively. Yet again, an increased concentra-
tion of 4MP [43.2% for 2MP/4MP (K = 23.5) and 38.2%
for 3MP/4MP (K=26.3)] instigated a signifcant selectivity
shift towards 4MP and yielded complexes containing 94.7
and 94.2% of this guest, respectively.
space group, while SED·PYR adopted the monoclinic crys-
tal system and P21 space group.
Figure 3a‒d represents the calculated voids after guest
removal for the four complexes using Mercury software
[17]; the voids represent the empty spaces in the crystal that
were able to hold a spherical probe with a radius of 1.2 Å.
Host OED accommodates the PYR, 3MP and 4MP guests
in discrete cavities, one guest in each in the former two, and
two in the latter. The complex that resulted from SED and
PYR showed that four of the guests occupy a single convo-
luted c-shaped cavity in the crystal structure of SED.
The more signifcant non-covalent interactions that were
present in the four complexes are provided in Table 4. Inter-
molecular (host)CH···π(host) interactions ranging between
2.63 and 3.00 Å (86°‒164°) in each which are responsible
for the stabilization of the host geometry. These also experi-
enced numerous weak (host)π···π(guest) contacts while one
(guest)π···π(guest) interaction could also be identifed in each
of OED·2(4MP) and SED·PYR [5.845(1) Å and 5.521(3) Å,
respectively] owing to the proximity of the guests in these
instances. However, these are very weak indeed. C‒H···π
interactions were also evident between host and guest in both
OED·PYR and SED·PYR ranging between 2.74 and 2.97 Å
with angles of 144°‒162°. These two complexes also expe-
rienced other strong short contacts between the hosts and
guest. The former comprised two (host)C‒H···H‒C(guest)
Single crystal X‑ray difractometry analyses
The crystallographic data for the OED·PYR, 2OED·3MP,
OED·2(4MP) and SED·PYR complexes are provided in
Table 3. In the case of 2OED·3MP, the guest is disordered
around an inversion point and the nitrogen hydrogens of the
host are disordered over two positions. Furthermore, the
OED·PYR complex has the host nitrogen hydrogens and
the PYR guest disordered over two orientations, while one
PYR guest experiences disorder in the SED·PYR complex.
Finally, 4MP in its complex with OED, on the other hand,
displays no disorder. The three inclusion compounds with
OED all crystallized in the triclinic crystal system and P−1
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
Table 3 Crystallographic data for OED·PYR, 2OED·3MP, OED·2(4MP) and SED·PYR
OED•PYR
2OED•3MP
OED•2(4MP)
SED•PYR
Chemical formula
Formula weight
Crystal system
Space group
µ (Mo-Kα)/mm−1
a/Å
b/Å
c/Å
alpha/°
beta/°
C40H44N2O2•C5H5N
663.87
Triclinic
P−1
2C40H44N2O2•C6H7N
1262.67
Triclinic
P−1
C40H44N2O2•2C6H7N
771.02
Triclinic
P−1
C40H44N2S2•C5H5N
695.99
Monoclinic
P21
0.075
0.074
0.073
0.179
9.3676(3)
14.0406(4)
14.0621(4)
89.754(2)
78.014(2)
80.324(2)
1782.58(9)
2
9.3229(6)
13.6496(9)
14.4164(9)
97.746(3)
98.307(3)
105.408(3)
1721.0(2)
1
9.7502(6)
9.8653(5)
12.4309(7)
67.588(2)
81.443(2)
73.729(2)
1059.93(11)
1
10.2878(6)
26.2000(14)
27.6768(15)
90
91.794(2)
90
7456.4(7)
8
1.240
gamma/°
V/Å 3
Z
D(calc)/g cm−3
F(000)
1.237
712
1.218
678
1.208
414
2976
Temp./K
Restraints
Nref
200
0
8878
428
200
0
8602
467
200
0
5266
267
200
35
33,252
1769
Npar
R
wR2
S
0.0579
0.1561
1.04
0.0426
0.1153
1.02
0.0414
0.1171
1.04
0.0514
0.1346
1.03
θ min–max/°
Tot. data
Unique data
1.5, 28.4
38,781
8878
1.9, 28.4
77,376
8602
2.2, 28.3
26,341
5266
0.7, 28.4
106,179
33,252
26,420
Observed data
6185
7346
4158
[I>2.0 sigma(I)]
Rint
0.032
1.000
0.025
0.998
0.021
1.000
0.026
1.000
Dfrn measured
fraction θ full
Min. resd. dens. (e/Å3)
Max. resd. dens. (e/Å3)
−0.88
0.86
−0.28
0.33
−0.17
0.30
−0.68
1.30
The unit cells for the OED·PYR, 2OED·3MP, OED·2(4MP) and SED·PYR complexes are presented in Fig. 2a‒d
interactions (2.15, 2.16 Å and 116°, 151°), while the latter
experienced one (host)C‒H···H‒C(host) (2.18 Å and 140°),
and one favourable (guest)C–H···C‒S(host) contact (2.69 Å
and 175°). Most remarkably, however, is the observation
that only the OED·2(4MP) complex experiences a particu-
larly stabilizing classical (host)N‒H···N‒C(guest) hydrogen
bond measuring 3.304(2) Å (D···A) [170.9(14)°] which cor-
relates with the signifcant preference of OED for 4MP in the
competition experiments. The stereoview provided in Fig. 4
illustrates this important interaction more clearly.
and diferential scanning calorimetry (DSC) and the result-
ant traces, together with the derivative of the TG (DTG),
are displayed in Fig. 5a‒d. The complexes were heated at
10 °C min−1 from 45 to 260 °C and the thermal data from
these are summarized in Table 5.
The expected guest mass losses correlate reasonably well
with those obtained in these experiments upon removal of
all of the guest through heating [OED·PYR 13.2, 11.9,
2OED·3MP 7.6, 7.4, OED·2(4MP) 24.2, 24.2 and SED·PYR
10.7, 11.4%]. Figure 5a, b and d show a convoluted guest
release process for the OED·PYR, 2OED·3MP and
SED·PYR complexes, respectively, while 4MP is released
in a clear single step from the crystals of OED.
Thermal analyses
The successfully formed complexes of hosts OED and
SED were subjected to thermogravimetric analysis (TG)
For complexes formed by OED, both Ton (the onset tem-
perature of the guest release process estimated from the
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
Fig. 3 The calculated voids in
a OED·PYR, b 2OED·3MP, c
OED·2(4MP) and d SED·PYR;
host compounds are represented
in a wireframe style and the
voids in a dark yellow colour
Table 4 A summary of the signifcant host‒host and host‒guest interactions in OED·PYR, 2OED·3MP, OED·2(4MP) and SED·PYR
Interactions
OED•PYR
2OED•3MP
OED•2(4MP)
SED•PYR
(host)π···π(guest)
4.832(1)‒5.969(1) Å
5.042(1)‒5.692(2) Å 4.950(1)‒5.953(1) Å
4.990(3)‒5.928(4)
Å
[7—major guest, 6—minor guest] [4]
[7]
[18‒major guest,
5‒minor guest]
C‒H···π
2.74‒2.91 Å, 144‒154°
None
None
2.87 Å, 156°
2.92 Å, 162°
2.80 Å, 153°
2.97 Å, 149°
(host 1)CH···π(guest 1)
(guest 1)p-ArH···π(host 1)
(guest 2d1)o-ArH···π(host 1)
(guest 2d1)m-ArH···π(host 2)
(guest 2d2)o-ArH···π(host 2)
Hydrogen bonding
None
None
None
3.304(2) Å, 170.9(14)°, None
(host 1)N‒H···N‒C(guest 1)
≪
(host 1)m-ArH···H‒C(guest 1d2) 2.15 Å, 116°, ≪
None
2.18 Å, 140°, ≪
2.69 Å, 175°, ≪
(host 1)C‒H···H‒C(guest 1d2)
(host 1)m-ArH···H‒C(host 2)
(guest 1)p-ArH···C‒S(host 2)
2.16 Å, 151°, ≪
The host and guest in each complex are given each a diferent number because of the diferent chemical environments they fnd themselves in,
with respect to each other
The major host and guest are indicated by a ‘d1’ while the minor host and guest are indicated by a ‘d2’ after the appropriate number
≪ Denotes contacts than this sum minus 0.2 Å. The number of □···□ interactions are provided in square brackets
1 3

Journal of Inclusion Phenomena and Macrocyclic Chemistry
Experimental
General
All chemicals were purchased from Merck and used without
further purifcation. 1H-NMR spectra were obtained using
a 400 MHz Bruker 400 Ultrashield Plus spectrometer, with
CDCl3 as the solvent, and analysed using Bruker TopSpin
3.2 data software.
SCXRD experiments were performed on the success-
fully formed complexes from the single solvent experiments
for both hosts OED and SED. These difraction data were
obtained at 200 K using a Bruker Kappa Apex II difrac-
tometer utilizing a graphite-monochromated Mo Kα radia-
tion (λ=0.71073 Å). The data were analyzed by means of
APEXII data software while the SAINT program was used
for data reduction and cell refnement [18]. The structures
were solved with SHELXT-2018/2 [19] using a dual-space
algorithm. SHELXL-2018/3 [20], with SHELXLE [21] as
a graphical interface, was used to refne the structures by
employing the least-squares procedure. All atoms, excluding
hydrogen, were refned anisotropically. Absorption efects
present in the data were corrected for using the numerical
method implemented in SADABS [18]. The Mercury 3.10.1
software package [22] was used to construct fgures display-
ing the unit cells as well as for calculating the voids present
in the crystal after removal of the guest from the packing
calculation. The complexes were deposited at the Cam-
bridge Crystallographic Data Centre with CCDC numbers
1918458 (OED•PYR), 1918459 (2OED•3MP), 1918460
[OED•2(4MP)] and 1918461 (SED•PYR).
Fig. 4 Stereoview illustrating the hydrogen bond (blue line) between
OED and 4MP
DTG and indicative of relative thermal stabilities) [17] and
the Tp (obtained from the peak on the DTG trace that repre-
sents guest loss) values are greater for the complex contain-
ing the preferred 4MP guest (77.0 and 98.7 °C) relative to
these temperatures for the remaining two complexes. This
too is in accordance with the enhanced selectivity of OED
for 4MP in the competition experiments.
Conclusions
N,N′-Bis(9-cyclohexyl-9-xanthenyl)ethylenediamine (OED)
was demonstrated to be a highly efective host compound in
the presence of PYR and the MPs, including each of PYR,
3MP and 4MP in single solvent experiments; however, it
failed to form a complex with 2MP. This host, furthermore,
displayed remarkable selectivity for 4MP when recrystal-
lized from various equimolar mixtures containing this guest,
and a selectivity order of 4MP (92.8%)≫PYR (6.0%)>3MP
(0.9%)>2MP (0.3%) was obtained from the corresponding
quaternary guest solvent mixture. On the other hand, N,N′-
bis(9-cyclohexyl-9-thioxanthenyl)ethylenediamine (SED)
was rather inefective in this regard, only including PYR,
and only in the single solvent experiments. Surprisingly, this
host did not form complexes when recrystallized from these
solvent mixtures, even those where PYR was present.
The SCXRD analyses showed that only the OED·2(4MP)
complex possessed a hydrogen bond between the host and
guest, and this observation explains the high afnity of OED
for 4MP. Thermal analyses also supported this host prefer-
ence in that the complex that displayed increased Ton and Tp
values was that containing the preferred 4MP guest.
DSC and TG experiments were conducted on all four of
the complexes. The thermal data were obtained using a Per-
kin Elmer Simultaneous Thermal Analyzer (STA) 6000 and
analysed using Pyris Series data software. Samples were
placed in a ceramic pan and an empty open ceramic pan
was used as a reference in these experiments, which were
conducted in high purity nitrogen gas, and samples were
heated at 10 °C min−1 from about 45 to 260 °C.
Owing to instrument availability, two GC–MS methods
were used to analyse the various PYR/MP experiments: (a)
an Agilent 7890A gas chromatograph, ftted with an Agilent
5975C VL mass spectrometer, was equipped with an Agilent
J&W DB-wax column. An initial temperature of 50 °C was
held for 1 min, followed by a heating ramp of 0.5 °C min−1
until 54 °C was attained, and this temperature was main-
tained for 5 min; (b) a Young Lin YL6500 gas chromato-
graph equipped with an Agilent J&W Cyclosil-B column
was employed. The latter GC system was heated to an ini-
tial temperature of 50 °C and maintained here for 2 min.
This was followed by a heating ramp of 30 °C min−1 until
100 °C was reached, and this was followed by yet another
Therefore, in this work, OED demonstrated that it is a
superior host compound for the enclathration of 4MP from
mixtures of these solvents, displaying near-complete selec-
tivity for this guest (92.8%) when recrystallized from an
equimolar quaternary mixture of the title guest solvents.
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Journal of Inclusion Phenomena and Macrocyclic Chemistry
Fig. 5 Overlaid TG (red), DSC (blue) and DTG (green) traces obtained from thermal analyses on the a OED·PYR, b 2OED·3MP, c
OED·2(4MP) and d SED·PYR complexes
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Journal of Inclusion Phenomena and Macrocyclic Chemistry
Table 5 Thermal data for the OED·PYR, 2OED·3MP, OED·2(4MP)
were treated in the same manner as in the single solvent
experiments. GC–MS was employed in order to determine
the guest:guest ratios here (with dichloromethane as the
solvent), while 1H-NMR spectroscopy provided the overall
H:G ratios.
and SED·PYR complexes
Complex
Ton (°C)a
Tp (°C)b
Theoretical
Observed
mass loss (%) loss (%)c
OED·PYR
67.7
78.9
125.9
208.6
95.2
11.9
7.4
13.2
7.6
Competition experiments using varied molar
concentrations of binary guest mixtures
2OED·3MP
76.7
164.5
170.3
180.8
185.7
195.3
226.5
98.7
OED and SED (0.05 g) were independently recrystallized
from binary mixtures of PYR and the MP isomers but
the concentrations of these guests were varied (a total of
5 mmol was used). The molar guest 1:guest 2 ratios ranged
from 20:80 to 80:20. Vials were treated as per the equimo-
lar experiments and the crystals that formed as well as the
solution from which they formed were analysed by means
of GC–MS. The host selectivity profles (Fig. 1a–f) were
obtained by plotting the molar fraction of the guest in the
crystal (Z) against that of the same guest in the solution
(x). The selectivity coefcient for the resultant selectivity
profles was calculated using the equation KA:B = ZA/ZB x
XB/XA, where XA +XB =1 [23]. The mole fraction of guest
A in the liquid mixture is given as XA and the amount of the
same guest present in the crystal as ZA.
OED·2(4MP)
SED·PYR
77.0
73.3
24.2
11.4
24.2
10.7
86.7
214.1
aOnset temperature for guest release (Ton) is estimated from the DTG
trace
bDTG peak temperature (Tp) representing the temperature at which
guest release is most rapid
cObserved mass loss was calculated from the TG trace
temperature ramp of 1.5 °C min−1 until 102 °C was attained.
Finally, the temperature was ramped at 0.5 °C min−1 to reach
103 °C.
Acknowledgements Financial support is acknowledged from the Nel-
son Mandela University and the National Research Foundation (NRF).
Compliance with ethical standards
Synthesis of host OED and SED
Conflict of interest There are no conficts to declare.
Host OED and SED were synthesized according to a previ-
ously published procedure [16].
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