Host compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(?)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation

Article abstract of DOI:10.1016/j.tet.2018.04.039

In this work, we have compared the host abilities of closely related compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(?)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) when these were recrystallized from single and mixed toluidine guests. Significant differences in host behaviour and selectivities were revealed and these were explained by means of single crystal diffraction experiments. Thermal analyses were used to determine the relative complex stabilities, and these data correlated exactly with the host selectivity orders for both TETROL and DMT.

Full text of DOI:10.1016/j.tet.2018.04.039

Tetrahedron xxx (2018) 1e8
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol
(TETROL) and (2R,3R)-(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-
1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative
investigation
Benita Barton*, Sasha-Lee Dorfling, Eric C. Hosten, Pieter L. Pohl
Department of Chemistry, PO Box 77000, Nelson Mandela University, Port Elizabeth, 6031, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, we have compared the host abilities of closely related compounds (þ)-(2R,3R)-1,1,4,4-
tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-
1,4-diol (DMT) when these were recrystallized from single and mixed toluidine guests. Significant dif-
ferences in host behaviour and selectivities were revealed and these were explained by means of single
crystal diffraction experiments. Thermal analyses were used to determine the relative complex stabil-
ities, and these data correlated exactly with the host selectivity orders for both TETROL and DMT.
© 2018 Elsevier Ltd. All rights reserved.
Received 26 February 2018
Received in revised form
9 April 2018
Accepted 15 April 2018
Available online xxx
Keywords:
Host-guest chemistry
Supramolecular chemistry
Isomeric toluidines
TETROL
DMT
1. Introduction
contribute towards their crystallinity.
The number of literature reports each year covering aspects of
Host-guest chemistry is that field of supramolecular chemistry1
in which host compounds, in the presence of particular guests, are
able to enclathrate these and, in so doing, form complexes with
them. Typically, the host material is a crystalline solid, while the
guests may be gases, liquids or solids, but more usually liquids.
Host-guest complexes are ordinarily held together by means of
non-covalent interactions such as van der Waals attractive forces,
host-guest chemistry is overwhelming as chemists attempt to un-
derstand better the underlying principles involved. Not only this,
but host-guest chemistry has a myriad useful applications in the
chemistry realm. Host compounds are able to serve as separation
agents for racemates8 as well as structural isomers,9e14 and have
been utilized in modified stationary phases for chromatographic
applications.15 Furthermore, host materials find application in both
chemosensors and biosensors,16e18 while optically pure host
compounds often find further use as catalysts in asymmetric syn-
theses, as demonstrated by the TADDOL class of compounds.15
Our research team focuses on the employment of host com-
pounds for the separation of structural isomers, which is ordinarily
quite difficult to achieve by conventional means owing to their
similar physical properties. During these investigations, we found
that both (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol
(TETROL) and a dimethoxy derivative thereof, (2R,3R)-(ꢀ)-2,3-
dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT), have the
ability to form inclusion complexes with selected toluidine
(methylaniline) isomers [o-toluidine (o-TOL), m-toluidine (m-TOL)
and p-toluidine (p-TOL)], the boiling points of which range be-
tween 200 and 203 ꢁC (Scheme 1). The toluidines are important
pꢀ
p
and CHꢀ
p
interactions, ion pairing and hydrogen bonding.2
There have been a number of proposed general structures for
the design of novel and effective host compounds,3e7 and it is
possible to summarise the more salient characteristics of these.
Successful host compounds oftentimes (i) have hydrogen bonding
capabilities in order to stabilize the hostꢀguest interaction, (ii)
have bulky, hydrophobic substituents (such as aromatic moieties)
that provide a surrounding factor which surround the guest mole-
cules in the crystal, (iii) are crystalline to facilitate separation of the
guest from the host, and (iv) have rigid frameworks which
* Corresponding author.
E-mail address: benita.barton@mandela.ac.za (B. Barton).
https://doi.org/10.1016/j.tet.2018.04.039
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

2
B. Barton et al. / Tetrahedron xxx (2018) 1e8
Table 1
H:G ratiosa for the single solvent experiments using TETROL and DMT as hosts, and
the toluidine isomers as guests.
Host
Guest
H:G ratio
TETROL
TETROL
TETROL
DMT
DMT
DMT
o-TOL
m-TOL
p-TOL
o-TOL
m-TOL
p-TOL
eb
2:3
2:3
2:1
2:1
2:1
a
Determined using 1H NMR spectroscopy with CDCl3 as the deuterated solvent.
No inclusion occurred.
b
Information, Figs. 1S and 2S show the 1H NMR spectra for
2TET∙3m-TOL and 2DMT∙o-TOL, respectively, as representative
examples).
2.2. Competition experiments
In order to ascertain whether these host compounds display any
selective behaviour in the presence of mixed guests, each host
material (approximately 0.3 mmol) was dissolved, in vials, in
equimolar binary and ternary mixtures of these guests (approxi-
mately 5 mmol of each). The vessels were closed and stored at 0 ꢁC
so as to maintain the equimolar condition. Once crystallization
occurred, the formed solids were treated as in the single solvent
experiments. GC-MS was selected as the more appropriate quan-
titative analytical technique for these complexes owing to the
overlap of guest-guest resonance signals in the 1H NMR spectra.
CH2Cl2 was used as the dissolution solvent in each instance. Table 2
summarizes the data so-obtained, where the preferred guest is
shown in bold.
The recrystallization of TETROL and DMT from the various
equimolar guest mixtures afforded mixed complexes in each case,
with the exception of the experiment comprising TETROL and the
equimolar binary guest mixture o-TOL/m-TOL, where crystalliza-
tion failed to occur. However, DMT, in an equivalent experiment,
did indeed furnish crystals, and these contained a significantly
larger amount of o-TOL (72.5%) relative to m-TOL. When TETROL
was recrystallized from o-TOL/p-TOL, the host displayed high
selectivity for the para isomer, extracting 83.5% of this isomer from
the mixture, while DMT was somewhat more ambivalent, showing
Scheme 1. Structures of host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-
1,2,3,4-tetraol (TETROL) and (2R,3R)-(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-
1,4-diol (DMT), and guests o-toluidine (o-TOL), m-toluidine (m-TOL) and p-toluidine
(p-TOL). In brackets beneath each guest structure is listed its boiling point.
industrial chemicals in that they are predominantly used as sol-
vents and chemical intermediates for the production of antioxi-
dants, pharmaceuticals, agricultural and rubber chemicals, and
hence our interest in their facile separation.19 We discovered that
the two title host compounds display marked differences in the
extent of their selectivities for these guests, despite their structural
similarities, and explore this phenomenon using single crystal X-
ray diffraction experiments and thermal analyses, and report on
these findings here.
2. Results and discussion
Hosts TETROL and DMT were readily prepared in moderate
yield according to published procedures.10,11
Table 2
2.1. Single solvent complex formation
H:G ratiosa for the equimolar mixed solvent experiments using TETROL and DMT as
hosts, and the toluidine isomers as guests.
TETROL and DMT were individually assessed for their host
abilities in the presence of each of the toluidine isomers. Therefore,
each host (approximately 0.1 g) was dissolved in an excess of the
guest (in the case of p-TOL, which is a solid at room temperature,
ethanol was added as co-solvent to achieve this). The vials were left
open to the ambient atmosphere, which facilitated the crystalli-
zation process. The so-formed crystals were collected by means of
vacuum filtration, washed efficiently with low boiling petroleum
ether (40e60 ꢁC) to remove superficial guest solvent, and dried.
These solids were analysed by means of 1H NMR spectroscopy,
using CDCl3 as the deuterated solvent, to determine if inclusion had
occurred. Integration of relevant host and guest resonances pro-
vided the host:guest (H:G) ratio in each case, and these are sum-
marized in Table 1.
Host
o-TOL
m-TOL
p-TOL
Guest ratios (%e.s.d.s)b
H:G ratio
TETROL
TETROL
x
x
x
ec
ec
x
x
x
16.5:83.5
(0.3)
29.9:70.1
(0.4)
14.2:27.3:58.5
(0.1) (0.6) (0.7)
72.5:27.5
(0.1)
46.7:53.3
(0.1)
2:3
TETROL
TETROL
DMT
x
x
x
2:3
2:3
2:1
2:1
2:1
2:1
x
x
x
DMT
x
x
x
DMT
x
x
28.7:71.3
90.8)
40.1:15.7:44.2
(0.6) (1.1) (0.4)
DMT
x
TETROL favoured the 2:3 H:G ratio when including guest sol-
vents m-TOL and p-TOL (Table 1). o-TOL was not enclathrated in
this way. On the other hand, DMT included all three of these iso-
mers and consistently with a H:G ratio of 2:1 (In the Supplementary
a
Determined using GC-MS with CH2Cl2 as the dissolution solvent.
These experiments were carried out in triplicate, and percentage estimated
b
standard deviations (%e.s.d.s) are provided in parentheses.
c
Crystals failed to form.
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

B. Barton et al. / Tetrahedron xxx (2018) 1e8
3
only a slight preference for p-TOL (53.3%). Using m-TOL/p-TOL as
the solvent system resulted in very similar data for both hosts, with
TETROL extracting 70.1% and DMT 71.3% p-TOL. The ternary ex-
periments provided the host selectivity for the three guests and
these are in the order p-TOL (58.5%) > m-TOL (27.3%) > o-TOL
(14.2%) and p-TOL (44.2%) > o-TOL (40.1%) > m-TOL (15.7%) for
TETROL and DMT, respectively. Hence, while both hosts are selec-
tive for the para isomer, the extent of this selectivity is markedly
different: TETROL usually displays significantly higher preferential
behaviour than DMT. Furthermore, DMT favoured o-TOL relative to
m-TOL, while the opposite was true for TETROL.
We subsequently mixed various combinations of two guests in
unequal molar amounts, and recrystallized each of the hosts from
these binary mixtures. The data from such experiments would
provide information on whether the selectivities of these hosts are
dependent on the amount of each guest present. In order to achieve
this, we analysed, by means of GC-MS, both the crystals that
resulted from each experiment (Z) and also the mother liquor from
which the crystals had formed (X). A plot of Z against X, therefore,
afforded a selectivity profile for each host compound. Note that
since TETROL failed to furnish crystals from the o-TOL/m-TOL
mixture, the selectivity profile of the host for this solvent mixture
could not be determined. Fig. 1aee display the results. (The linear
plot in each figure is hypothetical, and represents the behaviour of
the host if it were completely unselective, and has been inserted for
ease of comparison with the experimental data.)
ortho isomer than it is when p-TOL is mixed with the meta isomer.
The selectivity coefficient, K,19 was determined to be 1.9 (p-TOL/m-
TOL) and 10.0 (p-TOL/o-TOL). DMT, on the other hand, displays very
similar selectivity for p-TOL and o-TOL when these guests are
mixed with m-TOL (Fig. 1c and e) and, unsurprisingly, K was
comparable in both experiments (2.62 and 2.58, respectively). An
assessment of Fig. 1b and d shows the striking selectivity differ-
ences between the two hosts when recrystallized from p-TOL/o-
TOL mixtures: while both hosts are selective for p-TOL, the extent
of the selectivity is significantly different, with DMT displaying a
very low selectivity for this isomer (K ¼ 1.2, Fig. 1d) compared with
TETROL (K ¼ 10.0).
We were determined to investigate the reasons for the selec-
tivity differences between the two host materials, and conse-
quently carried out single crystal diffraction experiments on
suitable crystals that formed from each of the single solvent
complexes.
2.3. Single crystal diffraction experiments
Each of the single solvent complexes of TETROL and DMT with
the respective guests were subjected to single crystal X-ray
diffraction experiments. These experiments were conducted at
200 K using a Bruker Kappa Apex II diffractometer with graphite-
monochromated Mo K
a
radiation (
l
¼ 0.71073 Å). APEXII and
SAINT were used for data collection, and cell refinement and data
reduction, respectively.20 SHELXT-201421 was used to solve the
structures, and refined by least-squares procedures using SHELXL-
2017/1;21 here, SHELXLE22 served as a graphical interface. All non-
hydrogen atoms were refined anisotropically, and these were
When considering the selective behaviour of TETROL when
recrystallized from p-TOL/m-TOL and p-TOL/o-TOL (Fig. 1a and b,
respectively), it is clear that the host is significantly more selective
for p-TOL when this guest is mixed in various proportions with the
Fig. 1. Selectivity profiles for (a) TETROL/p-TOL/m-TOL, (b) TETROL/p-TOL/o-TOL, (c) DMT/p-TOL/m-TOL, (d) DMT/p-TOL/o-TOL and (e) DMT/o-TOL/m-TOL experiments.
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

4
B. Barton et al. / Tetrahedron xxx (2018) 1e8
placed in idealized geometrical positions in a riding model. Data
were corrected for absorption effects using the numerical method
implemented in SADABS.20 The H atoms of the hydroxyl groups of
TETROL were allowed to rotate with a fixed angle around the CeO
bonds to best fit the experimental electron density (HFIX 147 in the
SHELX program suite).21 The crystal data for all complexes were
deposited at the Cambridge Crystallographic Data Centre [CCDC
1823424 (2TET∙3m-TOL), 1823425 (2TET∙3p-TOL), 1823803
(2DMT∙o-TOL), 1823804 (2DMT∙m-TOL) and 1823805 (2DMT∙p-
TOL)].
Table 3 contains a summary of the relevant crystallographic data
obtained for these complexes. The TETROL/m-TOL inclusion com-
pound crystallizes in the triclinic crystal system and P1 space group,
while that containing p-TOL crystallizes in the orthorhombic
crystal system and P212121 space group. The three DMT complexes
all experience isostructural host packing (monoclinic, C2), and each
guest displays symmetry-generated disorder which is well-
modelled. Note that the nitrogen-bound hydrogens in the third
guest in 2TETROL∙3m-TOL and 2TETROL∙3p-TOL, as well as the
guests in each of the three DMT complexes, could not be located
owing to the disorder in these guests.
Unit cells for 2TETROL∙3m-TOL, 2TETROL∙3p-TOL and
2DMT∙p-TOL (as representative example for the three DMT com-
plexes due to the likeness of DMT's packing with the toluidine
guests) are displayed in Fig. 2aꢀc, respectively, while Fig. 2def are
as a result of the removal of the guest molecules from the packing
calculation in the Mercury software program in order to visualize
the nature of the guest accommodation, whether in channels or
isolated cavities.
Both complexes with TETROL show that the guests are accom-
modated within highly constricted channels, while guests in the
DMT complexes all experience discrete cavity occupation.
In order to determine the reasons for the host selectivity
behaviour differences, we analysed the hostꢀguest interactions
from these diffraction data, and these are provided in Table 4.
Immediately evident from these data is the reason for the high
selectivity displayed by TETROL for -p-TOL: the number of
hostꢀguest interactions experienced in this complex far surpasses
those in the complex containing m-TOL. This is true for
pꢀ
p, CHꢀ
p
and the various other short contacts that are possible. Furthermore,
both ordered guest molecules in 2TETROL∙3m-TOL function as
hydrogen bond acceptors with an hydroxyl group of the host
molecule [2.722(3) Å, 165ꢁ and 2.771(3) Å, 160ꢁ, respectively)]
while the disordered third guest here does not experience an
interaction of this type. The case is similar for the 2TETROL∙3p-TOL
complex, the interactions to each of the ordered guests measuring
2.731(3) Å, 158ꢁ and 2.710(3) Å, 165ꢁ; once more, the third guest is
not H-bonded in this way. These data suggest that hydrogen
bonding is important in these complexes and serves to anchor the
guests in one particular orientation, ensuring that these are ordered
in the crystal. When hydrogen bonding is absent, as in guest 3 in
these structures, the guest is able adopt more than one orientation,
thus resulting in the disorder that we observed.
While SCXRD data for the three complexes with DMT do not
explain the observed host selectivity order for these guests, these
data do, however, explain why TETROL is significantly more se-
lective than DMT. Firstly, the number of hostꢀguest interactions is
surprisingly contrasting in complexes with TETROL compared with
those of DMT, with the former experiencing substantially more of
these. In fact, DMT displays very few interactions indeed with the
three guests, and only
p p and one other short contact could be
ꢀ
found in each complex. Secondly, TETROL alone behaves as a
hydrogen bond donor to guests, and DMT, whilst having the ability
to do so by means of the two hydroxyl functionalities, does not
hydrogen bond at all in this way. It is suggested that the increased
selectivity of TETROL compared with DMT is due to the difference
Table 3
Crystallographic data for complexes of TETROL and DMT with the toluidine isomers.a
2TETROL∙3m-TOL
2TETROL∙3p-TOL
2DMT∙o-TOL
2DMT∙m-TOL
2DMT∙p-TOL
Chemical formula
Formula weight
Crystal system
Space group
2(C28H26O4)$2(C7H9N)$(C7H7Nb) 2(C28H26O4)$2(C7H9N)$(C7H7Nb) C30H30O4∙0.5C7H7Nb C30H30O4∙0.5C7H7Nb C30H30O4∙0.5C7H7Nb
1172.42
Triclinic
P1
1172.41
Orthorhombic
P212121
0.078
17.4913(5)
18.5146(5)
19.8236(6)
90
1014.21
Monoclinic
C2
0.079
17.3965(11)
11.9219(7)
14.2165(9)
90
1014.21
Monoclinic
C2
1014.21
Monoclinic
C2
m
(Mo-K
a
)/mmꢀ1
0.078
0.079
0.079
a/Å
b/Å
c/Å
10.7717(4)
11.8825(5)
13.4957(6)
86.693(2)
79.059(2)
71.473(2)
1608.08(12)
1
17.4485(12)
12.0156(8)
14.1121(10)
90
17.2804(19)
12.0944(14)
14.0931(16)
90
ꢁ
ꢁ
a
b
g
/
/
90
90
109.803(3)
90
110.179(2)
90
110.363(4)
90
ꢁ
/
V/Å3
6419.8(3)
4
2774.1(3)
2
2777.1(3)
2
2761.3(5)
2
Z
D(calc)/g.cmꢀ3
F(000)
Temp./K
Restraints
Nref
1.211
624
200
7
14904
808
1.213
2496
200
21
15966
790
1.214
1080
200
1
5477
1.213
1080
200
1
6833
372
1.220
1080
200
1
6617
350
Npar
372
R1
wR2
0.0405
0.1087
1.02
1.8, 28.3
56880
14904
0.0420
0.1066
1.02
1.6, 28.3
116349
15966
12034
0.027
0.0318
0.0892
1.04
2.1, 28.3
30507
5477
0.0339
0.0929
1.04
2.1, 28.3
54025
6833
6525
0.016
0.999
0.0358
0.0902
1.06
2.1, 28.3
22149
6617
5913
0.021
0.998
S
q
min-max/ꢁ
Tot. data
Unique data
Observed data [I > 2.0 sigma(I)] 12943
Rint
Dffrn measured fraction
Min. resd. dens. (e/Å3)
Max. resd. Dens. (e/Å3)
5040
0.020
1.000
ꢀ0.21
0.28
0.020
1.000
ꢀ0.15
0.19
q
full
1.000
ꢀ0.22
ꢀ0.23
ꢀ0.20
0.29
0.21
0.26
a
TETROL did not include o-TOL.
Nitrogen-bound hydrogen atoms could not be located due to the disorder in these guest molecules.
b
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

B. Barton et al. / Tetrahedron xxx (2018) 1e8
5
Fig. 2. Unit cells for (a) 2TETROL∙3m-TOL, (b) 2TETROL∙3p-TOL and (c) 2DMT∙p-TOL; calculated voids for (d) 2TETROL∙3m-TOL, (e) 2TETROL∙3p-TOL and (f) 2DMT∙p-TOL.
in the number of hostꢀguest interactions as well as the presence of
hydrogen bonding in complexes with the former host and absence
of these in the latter.
order to determine whether these results would explain the
observed selectivity orders for the two host materials. Overlaid
thermogravimetric (TG, green), differential scanning calorimetric
(DSC, brown) and the derivative of the TG (DTG) traces are provided
in Fig. 3aꢀe, which were obtained after heating each of the com-
plexes at 10 ꢁC.minꢀ1 from room temperature until approximately
250 ꢁC.
2.4. Thermal analysis
We analysed the five complexes by means of thermal analyses in
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

6
B. Barton et al. / Tetrahedron xxx (2018) 1e8
Table 4
Significant HꢀG interactions for complexes of TETROL and DMT with the toluidine isomers.a
Non-covalent
interaction
2TETROL∙3m-TOLb (number of 2TETROL∙3p-TOLb (number of 2DMT∙o-TOLc (number of 2DMT∙m-TOLc (number of 2DMT∙p-TOLc (number of
contacts)
contacts)
contacts)
contacts)
contacts)
p
ꢀp
4.7349(17)ꢀ5.8891(15) Å
5.959(3)ꢀ4.9399(15) Å
5.359(4)ꢀ5.891(4) Å
5.033(2)ꢀ5.971(2) Å
5.3154(15)ꢀ5.8618(15) Å
(15)
(25)
(8)
(8)
(4)
XH…
p
(guest 2)NH…
p
(host)
(guest 1)NH…
2.82(2) Å, 168(2)ꢁ
(guest 1)NH… (host)
2.67(3) Å, 130(2)ꢁ
(guest 2)NH… (host)
2.79(4) Å, 169(3)ꢁ
p
(host)
None
None
None
2.95(3) Å, 163(3)ꢁ
(guest 2)NH…
p(host)
p
2.54(6) Å, 138(5)ꢁ
(guest methyl)CH…
2.88 Å, 122ꢁ
p
(host)
p
(host Ar)CH…
2.95 Å, 162ꢁ
p(guest 3)
(host Ar)CH…
2.99 Å, 169ꢁ
(host Ar)CH…
2.90 Å, 164ꢁ
(host Ar)CH…
2.98 Å, 163ꢁ
(host Ar)CH…
2.84 Å, 157ꢁ
p(guest 3)
p(guest 3)
p(guest 3)
p(guest 3)
(guest 3 Ar)CH…
2.93 Å, 141ꢁ
p(guest 2)
Other short
contacts
(guest 2 Ar)CH∙∙∙CC(host Ar) (guest 1)NH…CC(host)
(host Ar)CH/N(guest)
2.52 Å, 177ꢁ
(guest Ar)CH/CH(host Ar) (host Ar)CH∙∙∙CC(guest
2.83 Å, 141ꢁ
2.81(2) Å, 163(2)ꢁ
(host Ar)CH…HC(guest 3
methyl)
2.88 Å, 156ꢁ
Ar)
2.89 Å, 144ꢁ
2.25 Å, 150ꢁ
(host Ar)CH…CC(guest 3)
2.81 Å, 142ꢁ
(host Ar)CH∙∙∙CC(guest 3)
2.80 Å, 137ꢁ
(guest 3 Ar)CH…CN(guest 2)
2.84 Å, 148ꢁ
H-bonding
(host)OH/N(guest 1)
2.722(3) Å, 165ꢁ
(host)OH…N(guest 2)
2.731(3) Å, 158ꢁ
None
None
None
(host)OH/N(guest 2)
2.771(3) Å, 160ꢁ
(host)OH/N(guest 1)
2.710(3) Å, 165ꢁ
a
H ¼ host, G ¼ guest.
b
c
Guests are labelled “guest 1”, “guest 2” and “guest 3” for the three guests in the unit cell; guest 3 showed disorder.
Nitrogen-bound hydrogen atoms could not be located due to the disorder in these guest molecules.
Relevant thermal data are summarized in Table 5, where Tb is
3. Conclusions
the boiling point of pure guest and Ton the temperature for the
onset of the guest release process (estimated from the DTG trace).
The function TonꢀTb is a measure of the relative thermal stabilities
of complexes,23 and is more valid when the host packing is iso-
structural. The less negative the value obtained, the more stable the
complex is. This function was therefore disregarded for the two
TETROL complexes (since these were not isostructural), and only
considered for the DMT inclusion compounds.
In this work, the host abilities of two similar compounds,
TETROL and DMT, were compared when crystallized in the pres-
ence of the toluidine isomers. TETROL preferred a 2:3 H:G ratio and
only included the meta- and para- isomers, while DMT formed
complexes with all three guests with a 2:1 ratio. Competition ex-
periments in which these hosts were recrystallized from mixed
guests showed TETROL to be significantly more selective than DMT,
and analyses of data from single crystal diffraction experiments
provided the reason: complexes with TETROL experienced a sub-
stantial number of various intermolecular hostꢀguest interactions,
while it was striking that DMT retained the guests by means of only
All of the complexes experience a guest release process that is
concomitant with the host melt. Expected mass losses for each of
these complexes were in close agreement with the mass losses
obtained experimentally. Furthermore, the thermal traces of the
TETROL complexes are more convoluted than those of the DMT
inclusion compounds. This is expected since the three guests in
2TETROL∙3m-TOL and 2TETROL∙3p-TOL do not all experience
hydrogen bonding with the host and will, therefore, in all likeli-
hood, be released at different temperatures, resulting in traces that
are more complex. On the other hand, the guests in each of the
complexes with DMT experience very similar (and few) in-
teractions with the host, none of which are hydrogen bonding, and
uncomplicated traces are the result. Using Ton as an indicator of the
relative thermal stabilities of the TETROL complexes, an order of p-
TOL (73.8 ꢁC) > m-TOL (56.4 ꢁC) is obtained, while TonꢀTb calcula-
p p interactions and a single other short contact. These observa-
ꢀ
tions, together with the fact that TETROL also behaves as a
hydrogen bond donor towards these guests while DMT does not,
account for these selectivity differences. Furthermore, thermal
analyses confirmed the selectivity orders for both hosts.
4. Experimental
4.1. General methods
Melting points (uncorrected) were recorded on a Stuart SMP10
melting point apparatus. 1H NMR spectra were obtained using a
400 MHz Bruker Avance Ultrashield Plus 400 Spectrometer. Ther-
mal experiments were carried out on a TA SDT Q600 Module sys-
tem and analysed using TA Universal Analysis 2000 data analysis
tions afford
a
p-TOL (ꢀ106.7 ꢁC) > o-TOL (ꢀ107.1 ꢁC) > m-TOL
(ꢀ107.5 ꢁC) order. Both of these correlate exactly and therefore
explain the host selectivity for these complexes.
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

B. Barton et al. / Tetrahedron xxx (2018) 1e8
7
Fig. 3. Overlaid TG (green), DSC (brown) and DTG (blue) traces for (a) 2TETROL∙3m-TOL, (b) 2TETROL∙3p-TOL, (c) 2DMT∙o-TOL, (d) 2DMT∙m-TOL and (e) 2DMT∙p-TOL.
Table 5
Relevant thermal data from the TG, DSC and DTG traces.
H:G complex
Tb/ꢁC
Ton/ꢁC
TonꢀTb/ꢁC
Mass loss observed/%
Mass loss expected/%
2TETROL∙3m-TOL
2TETROL∙3p-TOL
2DMT∙o-TOL
2DMT∙m-TOL
2DMT∙p-TOL
203.3
200.4
200.3
203.3
200.4
56.4
73.8
93.2
95.8
93.7
N/A
N/A
ꢀ107.1
ꢀ107.5
ꢀ106.7
27.1
27.5
11.3
10.5
10.8
27.4
27.4
10.5
10.5
10.5
software. Samples were placed in open platinum pans and an
empty platinum pan functioned as a reference. High purity nitro-
gen gas was used as purge gas here. GC-MS experiments were
carried out on an Agilent 7890A gas chromatograph fitted with an
Agilent 5975C VL mass spectrometer, and the column was a
Cyclosil-B column (30 m). From an initial temperature of 60 ꢁC, a
heating rate of 2.5 ꢁC.minꢀ1 was employed up to 130 ꢁC, with a final
hold time of 1 min.
4.2. Synthesis of TETROL and DMT
These host materials were synthesized in our laboratory ac-
cording to previous reports.10,11
4.2.1. TETROL10
Bromobenzene (22.99 g, 146.5 mmol), magnesium turnings
Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039

8
B. Barton et al. / Tetrahedron xxx (2018) 1e8
(3.94 g, 162.0 mmol) and (þ)-diethyl
L
-tartrate (5.00 g, 24.3 mmol),
Appendix A. Supplementary data
in a standard Grignard reaction, afforded a gum which recrystal-
lized from CH2Cl2/hexane/MeOH to afford TETROL as a white solid
(4.68 g, 10.9 mmol, 45%), mp 147e149 ꢁC (lit.,24, mp 150e151 ꢁC);
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2018.04.039.
[
a]
23 þ166ꢁ (c ¼ 9.32, CH2Cl2) {lit.,24, [
a
]
25 þ154ꢁ (c ¼ 1.2, CHCl3)};
D
D
nmax(solid)/cmꢀ1 3440 (br, OH), 3294 (br, OH), 3057 (Ar), 3033 (Ar),
1598 (Ar) and 1494 (Ar); dH(CDCl3) 3.86 (2H, d, 2COH), 4.44 (2H, d,
2HCOH), 4.72 (2H, s, 2CPh2OH) and 7.2e7.4 (20H, m, Ar); dC(CDCl3)
72.1 (HCOH), 81.7 (CPh2OH), 125.0 (Ar), 126.1 (Ar), 127.2 (Ar), 127.3
(Ar), 128.10 (Ar), 128.4 (Ar), 128.6 (Ar), 130.1 (Ar), 143.9 (quaternary
Ar) and 144.2 (quaternary Ar).
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ꢀ
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yielded DMT (3.76 g, 8.27 mmol, 65%) as a white solid, mp
23
124e126 ꢁC (lit.,25, mp 125e126 ꢁC); [
a
]
ꢀ154.5ꢁ (c. 0.27, CH2Cl2)
D
{lit.,25, [
a
]
ꢀ153ꢁ (c. 0.8, CHCl3)}; nmax(solid)/cmꢀ1 3576-3271 (br,
D
OH), 3025 (Ar), 2836 (O-CH3), and 1567 (Ar); dH(CDCl3)/ppm 2.60
(6H, s, 2OCH3), 4.46 (2H, s, 2HCOCH3), 4.87 (2H, s, 2CPh2OH [dis-
appears upon addition of D2O]), 7.17 (2H, m, Ar), 7.26 (4H, m, Ar),
7.32 (2H, m, Ar), 7.46 (4H, m, Ar) and 7.63 (8H, m, ortho-Ar);
dC(CDCl3)/ppm 61.0 (OCH3), 80.1 (CPh2OH), 85.3 (HCOCH3), 125.9
(Ar), 126.1 (Ar), 126.8 (Ar), 127.2 (Ar), 128.0 (Ar), 128.5 (Ar), 144.9
(quaternary Ar) and 145.6 (quaternary Ar).
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23. (a) Caira MR, Nassimbeni LR, Niven ML, Schubert W-D, Weber E,
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Financial support is acknowledged from the Nelson Mandela
University and the National Research Foundation (NRF). L. Bolo is
thanked for thermal analyses.
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Please cite this article in press as: Barton B, et al., Host compounds (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-
(ꢀ)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation, Tetrahedron
(2018), https://doi.org/10.1016/j.tet.2018.04.039