Host behaviour of related compounds, TETROL and DMT, in the presence of two different classes of aromatic guest compounds

Article abstract of DOI:10.1016/j.tet.2018.07.044

The host potential of two closely-related compounds, TETROL [(+)-(2R,3R)-1,1–4,4-tetraphenylbutane-1,2,3,4-tetraol] and DMT [(?)-(2R,3R)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol], were compared when recrystallized from two different classes of guests, namely toluene, ethylbenzene, cumene and aniline, N-methylaniline, N,N-dimethylaniline. TETROL formed complexes with only aniline and N-methylaniline (host:guest ratios, 2:3 and 2:4), while DMT included all six guests with a consistent ratio (2:1). Aniline competition experiments showed that TETROL preferred aniline (67%), followed by N-methyl- (29%) and N,N-dimethyl- (4%) aniline; surprisingly, this order was exactly reversed for DMT [N,N-dimethylaniline (62%) > N-methylaniline (32%) > aniline (6%)]. Crystal diffraction analyses revealed that TETROL formed stabilizing hydrogen bonds with guests, behaving as both donor and, for the first time, acceptor (in 2TETROL?4N-methylaniline). DMT did not form bonds of this type with any guests. Furthermore, the host packing was isostructural for all DMT complexes but was guest-dependent for TETROL. Thermal analyses showed that complex stabilities correlated precisely with the host preferences.

Full text of DOI:10.1016/j.tet.2018.07.044

Tetrahedron 74 (2018) 4754e4760
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Host behaviour of related compounds, TETROL and DMT, in the
presence of two different classes of aromatic guest compounds
*
**
Benita Barton , Lize de Jager , Sasha-Lee Dorfling, Eric C. Hosten, Cedric W. McCleland,
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:
Received 21 May 2018
Received in revised form
The host potential of two closely-related compounds, TETROL [(þ)-(2R,3R)-1,1e4,4-tetraphenylbutane-
1
,2,3,4-tetraol] and DMT [(ꢀ)-(2R,3R)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol], were
compared when recrystallized from two different classes of guests, namely toluene, ethylbenzene,
cumene and aniline, N-methylaniline, N,N-dimethylaniline. TETROL formed complexes with only aniline
and N-methylaniline (host:guest ratios, 2:3 and 2:4), while DMT included all six guests with a consistent
ratio (2:1). Aniline competition experiments showed that TETROL preferred aniline (67%), followed by N-
methyl- (29%) and N,N-dimethyl- (4%) aniline; surprisingly, this order was exactly reversed for DMT [N,N-
dimethylaniline (62%) > N-methylaniline (32%) > aniline (6%)]. Crystal diffraction analyses revealed that
TETROL formed stabilizing hydrogen bonds with guests, behaving as both donor and, for the first time,
acceptor (in 2TETROL∙4N-methylaniline). DMT did not form bonds of this type with any guests.
Furthermore, the host packing was isostructural for all DMT complexes but was guest-dependent for
TETROL. Thermal analyses showed that complex stabilities correlated precisely with the host
preferences.
9
July 2018
Accepted 20 July 2018
Available online 24 July 2018
Keywords:
Host-guest chemistry
Inclusion
DMT
TETROL
Toluene
Aniline
©
2018 Elsevier Ltd. All rights reserved.
1
. Introduction
Kuhn et al. [3] have reviewed chiral separations by capillary
zone electrophoresis and micellar electrokinetic capillary chroma-
tography, which often involve host-guest chemistry principles, and
have illustrated the potential of such methods. In particular are
mentioned the host materials cyclodextrin and chiral crown ethers
for these applications. Additionally, host materials may have the
ability to enclathrate drug actives and, in so doing, improve the
transport, activity, resistance, solubility, and overall drug delivery
of these actives into the human body [4]. Other plausible applica-
tions include the removal of hazardous materials from the envi-
ronment, improving the taste and stability of food products,
asymmetric synthesis, and gas storage [5e9].
We have recently reported on the host behaviour of (ꢀ)-(2R,3R)-
2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT, Scheme 1)
in the presence of various mixtures of xylenes [10] and anilines [11].
These investigations were prompted by the fact that each of the
guests in both series are employed as building blocks for a wide
variety of industrially-important products, and challenges have
been encountered in their isolation and purification [12,13]. TETROL
Host-guest chemistry is a burgeoning field within supramolec-
ular chemistry, and considerations of host-guest methodologies
and their applicability to the chemical industry are becoming
increasingly pertinent [1]. One promising application of host-guest
chemistry is the separation of mixtures of positional isomers which
typically have similar physical properties and, therefore, frequently
do not respond favourably to traditional separation methods [2].
Consequently, the selective inclusion by host materials of a
particular guest species from such mixtures is an attractive attri-
bute that may be exploited to potentially address this challenge. For
example, industrial processes relying on single isomers of each of
the cresols, xylenes and methylanisoles, amongst others, would
benefit considerably if a simple method existed for their purifica-
tion, since such isomers are widely used as precursors to an array of
valuable end-products.
*
Corresponding author.
[
(þ)-(2R,3R)-1,1e4,4-tetraphenylbutane-1,2,3,4-tetraol, Scheme 1]
*
* Corresponding author.
E-mail addresses: benita.barton@mandela.ac.za (B. Barton), s213337665@
is closely related to DMT in that its two secondary hydroxyl func-
tionalities are further derivatized as methoxyl moieties. This subtle
mandela.ac.za (L. de Jager).
https://doi.org/10.1016/j.tet.2018.07.044
0
040-4020/© 2018 Elsevier Ltd. All rights reserved.

B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
4755
Table 1
Host:guest (H:G) ratios of complexes obtained when TETROL and DMT were
recrystallized individually from the six aromatic guests species.
Guest
TETROL
DMT
a
a
a
Toluene
Ethylbenzene
Cumene
2:1
2:1
2:1
b
Aniline
N-Methylaniline
N,N-Dimethylaniline
2:3
2:1
2:1
2:1
c
b
2:4
a
b
a
These guests were not clathrated.
b
These results were published on a prior occasion and are inserted here for ease
of comparison [11].
Scheme 1. Structures of related hosts DMT and TETROL.
c
Subsequent diffraction analyses showed the asymmetric unit to contain two
host and four guest molecules.
change in host structure significantly changed the behaviour of the
host when recrystallized under the same conditions in the presence
of isomeric toluidine mixtures [14]: TETROL showed a marked in-
crease in selectivity compared with DMT, but both host materials
preferred the same guest (p-toluidine) in these competition
experiments.
In the present work, we have investigated and compared the
selective behaviour of TETROL and DMT when recrystallized from
guest solvents comprising two different classes of aromatic com-
pounds, namely the alkylated aromatics toluene, ethylbenzene and
cumene, and the aminated aromatics aniline, N-methylaniline and
N,N-dimethylaniline. Surprisingly, the preference order of DMT for
the anilines [11] contrasted with that of TETROL; however, the
extent of the selectivity for their preferred guests was comparable.
These observations are distinctly different from the results ob-
tained from the toluidine work, where TETROL was observed to be
significantly more selective than DMT [14]. We employed single
crystal diffraction analyses in order to ascertain the reasons for
these differences, and thermal analyses to investigate the stabilities
of all complexes formed, and report on these results here.
2.2.2. Equimolar mixed-solvent recrystallizations
We subsequently conducted competition experiments using
various combinations of the three alkylated and, independently,
the three aminated aromatics in order to determine the effect of
the availability of multiple guests on the inclusion behaviour of
the host. In each case, the host was recrystallized from equimolar
combinations of the guest solvent. The equimolar condition was
ꢁ
maintained by storing the vessels at 0 C after dissolution of the
host. Where crystals formed, these were processed as in the
single-solvent experiments. Table 2 (aminated aromatics) and 3
(alkylated aromatics) summarise the data obtained. Note that
since none of the alkylated aromatics were included by TETROL,
competition studies for this class of compounds and this host
were disregarded.
These data reveal that TETROL has a distinct preference for
including aniline whenever this compound was present in the
recrystallizing mixture (Table 2). From the aniline/N-methylani-
line and aniline/N,N-dimethylaniline binary mixtures, TETROL
extracted 68 and 95% aniline, respectively. An N-methylaniline/
N,N-dimethylaniline experiment, on the other hand, failed to
furnish crystals and when aniline was also added, a host prefer-
ence order of aniline (67%) > N-methylaniline (29%) > N,N-dime-
thylaniline (4%) was noted. In contrast to TETROL, DMT afforded a
host selectivity order of N,N-dimethylaniline (62%) > N-methyl-
aniline (32%) > aniline (6%) [11]. Furthermore, it is noteworthy
that the extent of these host selectivities are comparable (62, 32, 6
versus 67, 29, 4) though for different guests. The selectivity of DMT
in the aniline series appears to correlate with increasing polarity
of the aniline guest compound, while the opposite is true for
2
. Results and discussion
2.1. Synthesis of DMT and TETROL
Both host materials were prepared from naturally-occurring
(þ)-diethyl
L-tartrate using published methods [10,15].
2.2. Assessment of the inclusion ability of DMT and TETROL with the
alkylated and aminated aromatic guests
1
TETROL.
In the case of the alkyl benzenes, binary competition experi-
ments showed that DMT selected toluene (67%) and ethylbenzene
2
.2.1. Single-solvent recrystallizations
Single solvent experiments were performed by dissolving each
(63%) in preference to cumene (33 and 37%, respectively, Table 3).
host individually in an excess of the six aromatic guest solvents, and
the vessels left open under ambient conditions until crystallization
occurred. The resulting solids were collected by vacuum filtration,
washed with petroleum ether (b.p. 40e60 C), and analysed by
means of H NMR spectroscopy using CDCl
inclusion complex formation occurred, the H:G ratios were deter-
mined from appropriate host and guest compound resonance in-
tegrals. Table 1 summarises these results.
It is clear from this table that TETROL is significantly more
discriminating than DMT, including only aniline and N-methyl-
aniline from the list of six possible guests, and showed no affinity at
all for the alkylated benzenes. DMT, on the other hand, formed
complexes with all six solvents. Furthermore, H:G ratios in the case
of complexes with TETROL were guest-dependent with aniline and
N-methylaniline being included with 2:3 and 2:4 H:G ratios,
respectively. In contrast, DMT favoured the 2:1 ratio in every
instance.
When the host was recrystallized from an equimolar toluene/
ethylbenzene mixture, toluene was only marginally preferred
(51% vs 49%). A ternary competition experiment comprising all
ꢁ
three alkyl aromatics resulted in poor selectivity with an order
ethylbenzene (39%) > toluene (35%) > cumene (26%) being ob-
tained. On the face of it, the inclusion selectivity displayed by
DMT seems to correlate with the polarities of the guest com-
pounds insofar as it exhibited higher selectivity in a ternary
mixture of the three anilines (Table 2), while the inclusion
selectivity was poor in a ternary mixture of the relatively non-
polar alkyl benzene guests.
1
3
as the solvent. Where
1
The dipole values for aniline, N-methylaniline and N,N-dimethylaniline,
computed at the
uB97X-D/6-31G* level, are 1.69, 1.73 and 1.79, while those for
toluene, ethylbenzene and cumene are 0.33, 0.29 and 0.27 Debye, respectively.

4756
B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
Table 2
Host:guest (H:G) ratios of complexes obtained when TETROL and DMT were recrystallized from equimolar mixtures of the aniline guests.
a
Host
Aniline
N-Methylaniline
N,N-Dimethylaniline
Guest ratios (%e.s.d.sb)
Overall H:G ratio
TETROL
TETROL
TETROL
TETROL
x
x
x
68:32 (0.3)
95:5 (0.7)
(N/A)
67:29:4 (0.6)(0.6)(0.1)
15:85 (0.1)
15:85 (0.8)
2:3
2:3
N/A
2:3
2:1
2:1
2:1
2:1
x
x
x
c
x
x
x
x
x
x
c
DMT
DMT
DMT
c
x
x
x
c
x
x
41:59 (0.3)
6:32:62 (0.2)(0.2)(0.0)
c
DMT
x
Bold italic represents preferred guest.
a
Determined using GC-MS (see General Methods) and/or 1H NMR spectroscopy, as appropriate.
Experiments were conducted in triplicate, and parentheses contain the percentage estimated standard deviations (%e.s.d.s).
These results have been published on a prior occasion [11] and are inserted here for ease of comparison.
b
c
Table 3
hand, was guest-dependent: enclathration of aniline resulted in
solids which crystallised in the orthorhombic crystal system and
P2 2 2 space group, while the N-alkylated guest complex differed
1 1 1
Guest ratios in complexes obtained from competition experiments using DMT and
equimolar mixtures of the alkylbenzene guests
a,b
.
Toluene Ethylbenzene Cumene Guest ratios (%e.s.d.sc) Overall H:G ratio
from this (triclinic, P1).
x
x
x
51:49 (0.4)
67:33 (0.9)
63:37 (0.1)
2:1
2:1
2:1
Both toluene and cumene in complexes with DMT displayed
disorder owing to rotation about a two-fold axis. (Ethylbenzene, on
the other hand, showed several layers of disorder [10]). These
relatively non-polar guests were entrapped within the host crystal
x
x
x
x
x
x
35:39:26 (0.4, 0.1, 0.1) 2:1
Bold italic represents preferred guest.
by means of a number of weak
p
ꢀ
p interactions ranging between
a
Ratios determined using GC-MS.
4.570(6) and 5.996(3) Å. Toluene experienced no further interaction
b
TETROL's behaviour was not assessed in this investigation since it failed to
include any of the alkylated aromatics.
types while only one other short contact was noted in the cumene
c
inclusion compound involving the meta-aromatic C atom of the
Experiments were conducted in triplicate, and percentage estimated standard
ꢁ
deviations (%e.s.d.s) are given in parentheses.
guest and the para-aromatic H atom of the host (2.89 Å, 168 ).
Overall, the number and type of hostꢀguest interactions in these
complexes are strikingly few.
2.3. Single crystal X-ray diffraction analyses
Only one of the three guests in the asymmetric unit of
2TETROL$3aniline is disordered. Here, the two ordered aniline
Crystals of DMT alone and also its complexes with toluene and
molecules are anchored in position by means of strong hydrogen
bonds with the secondary hydroxyl groups of the host, measuring
2.746(3) and 2.763(3) Å (O/N), with angles of 165 and 167 ,
cumene were subjected to these X-ray diffraction analyses, as were
the complexes of TETROL with aniline and N-methylaniline. The
diffractions were conducted at 200 K employing a Bruker Kappa
ꢁ
respectively. The host functions as a H-bond donor in both cases.
The disordered aniline molecule does not experience an interaction
of this type. Similar observations were made when analysing
TETROL's 2:3 H:G complexes with the toluidines [14]. The asym-
metric unit of 2TETROL$4N-methylaniline comprises two host and
four guest molecules. Two of the four guests function as hydrogen
bond acceptors with secondary host hydroxyl groups, both
Apex II diffractometer with graphite-monochromated Mo K
a ra-
diation (
l
¼ 0.71073 Å). APEXII [16] was used for data collection and
SAINT [16] for cell refinement and data reduction. The structures
were solved using SHELXT-2014 [17] and refined by least-squares
procedures using SHELXL-2016 [18] with SHELXLE [19] as graph-
ical interface. Non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were placed in idealized geometrical positions in a
riding model. Data were corrected for absorption effects using the
SADABS [16] numerical method. All relevant crystal data were
deposited at the Cambridge Crystallographic Data Centre and may
be accessed free of charge via www.ccdc.cam.ac.uk/data_request/
cif [CCDC reference numbers 1828030 (2DMT$toluene), 1828031
ꢁ
measuring 2.738(2) Å (O/N), with angles 151 and 154 . Remark-
ably, the third is a donor to one of the tertiary host hydroxyls [O/N
ꢁ
3.019(3) Å, 152(2) ] which, to the best of our knowledge, is un-
precedented in the literature ꢀ to date, TETROL has only ever been
observed to function as a donor to guests that possess hydrogen
bonding capability and [14,15], interestingly, it is the secondary
hydroxyl groups that are largely involved. The fourth guest mole-
cule, once more, does not experience hydrogen bonding with the
host. Contrastingly, on no occasion does DMT retain its guests in the
crystal by means of hydrogen bonding when such guests have the
ability to perform as hydrogen bond donors and/or acceptors, as in
the aniline series [11]. This suggests that TETROL favours this
interaction type while DMT does not, which predisposes TETROL to
complex less readily with the various guests, as witnessed in
Table 1. DMT, however, does not employ hydrogen bonding to
stabilize guest retention, and so a wider variety of guests are able to
be enclathrated by it. This is affirmed by the fact that DMT readily
forms complexes with the alkyl aromatics, while TETROL does not
since these guests do not possess hydrogen bonding capability.
Fig. 1aꢀd depict the unit cells for 2DMT$toluene (as represen-
tative example of the isostructural complexes, with guests in
magenta colour and ball-and-stick representation), apohost DMT,
(
(
[
2
2
2DMT$cumene),
1828032
(DMT
apohost),
1827895
2TETROL$3aniline) and 1842472 (2TETROL$4N-methylaniline)].
Diffraction data for 2DMT$ethylbenzene (CCDC 1487592),
DMT$aniline (1577095), 2DMT$N-methylaniline (1577097) and
DMT$N,N-dimethylaniline (1577096) were deposited on prior
occasions [10,11].
Table 4 lists crystallographic data and refinement parameters for
DMT$toluene, 2DMT$cumene, DMT apohost, 2TETROL$3aniline
and 2TETROL$4N-methylaniline. Both the toluene and cumene
complexes experience isostructural host packing, crystallizing in
the monoclinic crystal system with C2 symmetry. In fact, all six
complexes relevant to the present discussion shared this iso-
structurality [10,11]. The crystal packing, however, collapsed when
guest was not present, as witnessed by the variation in crystal
2
1
system (tetragonal) and space group (I4 ) of the apohost material
(
Table 4). The host packing in complexes with TETROL, on the other

B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
4757
Table 4
Crystallographic data for 2DMT$toluene, 2DMT$cumene, DMT alone, 2TETROL$3aniline and TETROL$2N-methylaniline.
2
DMT$toluene 2DMT$cumene Apohost 2TETROL$3aniline
2TETROL$4N-methylaniline
2C28 $4C
Chemical formula
Formula weight
Crystal system
2C30 $C 2C30 $C 2C28 $2C N,C
H
30
O
4
7
H
8
H
30
O
4
9
H
12
C
30
H
30
O
4
H
26
O
4
H
6 7
6
H
5
Na
H
26
O
4
7 9
H N
1001.21 1029.27 1130.34
Orthorhombic
P2
0.080
454.54
Tetragonal
I4
0.078
10.2823(6)
10.2823(6)
23.8173(2)
90
640.79
Triclinic
P1
Monoclinic
C2
Monoclinic
C2
Space group
1
1 1 1
2 2
ꢀ
m
(Mo-K
a
)/mm 1
0.078
17.3412(6)
11.9827(4)
14.0871(5)
90
0.078
17.1139(6)
12.0772(5)
14.3270(5)
90
0.078
a/Å
b/Å
17.3680(9)
17.5435(9)
20.0346(10)
90
11.5756(6)
13.1533(7)
13.6373(6)
62.163(2)
89.734(2)
74.043(2)
1746.56(16)
2
c/Å
alpha/
beta/
ꢁ
ꢁ
109.892(2)
90
107.460(2)
90
90
90
90
90
ꢁ
gamma/
V/Å [3]
Z
2752.6(2)
2
2824.8(2)
2
2518.1(3)
4
6104.5(5)
4
F(000)
1068
1100
968
2400
684
Temp./K
200
200
200
200
200
Restraints
5
1
1
6
3
Nref
Npar
R
wR2
S
6037
326
6398
380
3129
156
0.0307
0.0826
1.09
2.2, 28.3
39639
3129
2982
0.020
1.000
ꢀ0.13
0.16
15216
758
0.0401
0.1135
1.04
1.5, 28.3
147780
15216
12442
0.023
1.000
ꢀ0.32
0.40
16209
893
0.0338
0.0788
1.02
1.7, 28.3
62431
16209
14356
0.020
0.0377
0.1008
1.03
2.1, 28.3
19477
6037
0.0351
0.0899
1.03
2.1, 28.3
26304
6398
ꢁ
q
minꢀmax/
Tot. data
Unique data
Observed data [I > 2.0 sigma(I)]
5479
5519
R
int
0.017
0.999
ꢀ0.33
0.31
0.020
1.000
ꢀ0.17
0.20
Dffrn measured fraction
Min. resd. dens. (e/Å )
Max. resd. dens. (e/Å )
q
full
1.000
3
ꢀ0.17
3
0.22
a
Nitrogen-bound hydrogen atoms could not be located since these guest molecules displayed disorder.
and the complexes of TETROL with aniline (hydrogen bonded
guests in yellow and those not hydrogen bonded in green) and N-
methylaniline (hydrogen bonded guests, orange; non-hydrogen
bonded guest, red), respectively. A stereoview is also provided in
Fig. 2 to illustrate the unusual hydrogen bond acceptor behaviour of
TETROL in the latter complex, involving the NꢀH hydrogen atom of
N-methylaniline and the tertiary host hydroxyl group.
3. Conclusion
DMT and TETROL, compounds that are related closely in
structure, display very different host abilities when recrystallized
from two different classes of guest solvents, namely toluene, eth-
ylbenzene, cumene on one hand, and aniline, N-methylaniline,
N,N-dimethylaniline on the other. TETROL failed to form complexes
with the alkyl aromatics, while each of these was included by DMT
with a 2:1 host:guest ratio. An equimolar ternary experiment
comprising these three guests showed that DMT was poorly se-
lective under these conditions. However, TETROL did form
complexes with aniline and N-methylaniline, while N,N-dimethy-
laniline was not clathrated. Host:guest ratios differed for the two
complexes formed. When TETROL was recrystallized from an ani-
line/N-methylaniline/N,N-dimethylaniline mixture, it displayed a
high preference for aniline; these results contrasted with similar
experiments conducted using these guests and DMT, where the
opposite selectivity order was observed. Single crystal X-ray
diffraction analyses showed that TETROL employs hydrogen
bonding with the aniline guests in order to stabilize each complex.
Previously, TETROL has been observed to behave as the donor in
such interactions, utilizing the secondary hydroxyl hydrogen
atoms. In the present case, TETROL functions unusually as a
hydrogen bond acceptor, employing the tertiary hydroxyls to
achieve this. This was revealed in the inclusion compound with N-
methylaniline, where one of these guests in the asymmetric unit
donated a hydrogen towards the tertiary host hydroxyl group. The
increased complexation ability of DMT relative to TETROL was
ascribed to the fact that TETROL, in this investigation, relies on
hydrogen bonding for guest retention, and so the guest should
have this capability. Therefore the three non-polar alkyl benzene
guests were not complexed while two of the anilines were. DMT is
less discerning since it does not rely on this interaction type in
order to stabilize the guest in the crystal. Finally, thermal analyses
showed that the stabilities of the novel complexes produced in this
2.4. Thermal analyses
The stabilities of the novel complexes formed in this study, i.e.
DMT$toluene, 2DMT$cumene, 2TETROL$3aniline and 2TETROL$
N-methylaniline, were determined through thermal analysis by
2
4
ꢁ
ꢀ1
heating in open platinum pans at 10 C.min . Fig. 3aꢀb illustrate
the overlaid thermogravimetric (TG) and the derivative thereof
(
DTG) traces that were obtained for the DMT and TETROL inclusion
compounds, respectively.
Table 5 summarises the relevant thermal data obtained from
these traces.
The expected and observed mass losses experienced by the four
complexes are all in close agreement (Table 5). Furthermore, ther-
mal events experienced by the complexes with TETROL are gener-
ally more convoluted than those with DMT, as expected, owing to
the isostructurailty of host packing in the latter and, additionally,
the presence of only a few hostꢀguest stabilizing interactions. Ton
,
the onset temperature of the guest release process which was
estimated from the derivative of the TG (DTG), serves as a measure
of the stabilities of the complexes, and these correlate exactly with
the selectivity orders of the two hosts: toluene and aniline are
released at significantly higher temperatures relative to cumene
and N-methylaniline in their respective crystals with DMT and
TETROL, reflecting the higher stabilities of the complexes of
2
DMT$toluene and 2TETROL$3aniline, which explains the prefer-
ence of the hosts for these guests as observed from competition
experiments.

4758
B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
Fig. 1. Unit cells for (a) 2DMT$toluene, (b) DMT alone, (c) 2TETROL$3aniline, and (d) 2TETROL$4N-methylaniline.
work correlate exactly with the guest preference order.
. Experimental
.1. General methods
Melting points were recorded on a Stuart SMP10 melting point
4
4
1
13
apparatus and are uncorrected. H- and C- NMR spectra were
obtained by means of a 400 MHz Bruker Avance Ultrashield Plus
400 spectrometer, and infrared spectra using a Bruker Tensor 27
Fourier Transform Infrared spectrophotometer. Gas chromatog-
raphy was performed using an Agilent Technologies 7890 A gas
chromatograph system connected to an Agilent Technologies
5975 C VL MSD mass spectrometer with a triple-axis detector. High
purity helium gas was used as the carrier gas. An Agilent J&W
Cyclosil-B column was used for the alkyl aromatics analyses, and
Fig. 2. Stereoview depicting the unusual behaviour of TETROL as a hydrogen bond
acceptor to one of the four N-methylaniline guests (turquoise); the guest that does
not hydrogen bond to the host is shown in blue.
the parameters were 30 m ꢂ 250
mm x 0.25 mm (calibrated). From

B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
4759
Fig. 3. Overlaid TG and DTG traces for (a) 2DMT$toluene and 2DMT$cumene, and (b) 2TETROL$3aniline and 2TETROL$4N-methylaniline.
ꢁ
ꢁ
ꢀ1
an initial temperature of 50 C, a heating rate of 2.5 C.min was
4.2. Preparation of hosts DMT and TETROL
ꢁ
employed up to 90 C with a final hold time of 1 min. For the ani-
lines analyses, an HP-5 column (30 m) was employed. The method
These host compounds were prepared according to published
procedures [10,15].
ꢁ
involved an initial 2 min hold time at 40 C, followed by a ramp of
ꢁ
ꢀ1
ꢁ
2
C.min until 160 C was reached, and then a hold time at this
ꢁ
ꢀ1
ꢁ
temperature for 5 min, and lastly a ramp of 20 C.min until 220 C
4
.2.1. Synthesis of TETROL [15].
R,R)-(þ)-Diethyl -tartrate (5.71 g, 27.7 mmol), phenyl-
magnesium bromide [prepared from magnesium turnings (4.06 g,
67 mmol) and bromobenzene (23.12 g, 147 mmol)] afforded a gum
which was dissolved in methanol, from which TETROL crystallised
was attained, and then a final hold time at this temperature for
(
L
ꢁ
1
0 min. The split ratio was 100:1 and inlet temperature 250 C.
Thermal analyses were carried out on a TA SDT Q600 Module sys-
tem and analysed using TA Universal Analysis 2000 data analysis
software. The solid complexes were placed in open platinum pans.
An empty platinum pan was employed as a reference, and high
purity nitrogen gas was used as the purge gas.
1
ꢁ
ꢁ
(
[
7.98 g, 18.7 mmol, 68%), mp 148e150 C (lit., [20], mp 150e151 C);
a
2
3
ꢁ
25
ꢁ
]
D
þ163 (c. 3.18, CH
2
Cl
2
) {lit., [20], [
a
]
D
þ154 (c. 1.2, CHCl
3
)};
ꢀ
1
n
max(solid)/cm 3525ꢀ3380 (br, OH), 3392ꢀ3146 (br, OH), 3057
(
Ar), 3031 (Ar), 1597 (Ar) and 1493 (Ar);
d
H
(CDCl
OH), 4.31 (2H, s, 2HCOH) and 7.00e7.30 (20H, m,
)/ppm 72.1 (HCOH), 81.7 (CPh OH), 125.0 (Ar), 126.1
Ar),127.1 (Ar),127.3 (Ar),128.4 (Ar),128.6 (Ar),143.9 (quaternary Ar)
and 144.2 (quaternary Ar) (See Supplementary data, Figs.1S and 2S).
3
)/ppm 3.82 (4H, br,
2
HCOH and 2CPh
2
Table 5
Ar);
d (CDCl
C
3
2
Thermal data for 2DMT$toluene, 2DMT$cumene, 2TETROL$3aniline and
(
2TETROL$4N-methylaniline.
ꢁ
a
Complex
T
on ( C)
Mass loss
Mass loss
expected (%)
observed (%)
4
.2.2. Synthesis of DMT [10].
Excess sodium hydride (6.0125 g, 55e65% suspension in mineral
2
2
2
2
DMT$toluene
DMT$cumene
TETROL$3aniline
TETROL$4N-methylaniline
78.5
69.1
70.9
41.1
9.2
9.1
11.7
24.7
33.4
12.3
25.9
32.2
oil), TETROL (5.48 g, 12.8 mmol) and methyl iodide (3.65 g,
25.9 mmol) afforded a gum which was triturated with petroleum
ether (40e60 C); this resulted in a white precipitate which was
ꢁ
a
Estimated from the DTG trace and is the onset temperature of the guest
release process.
recrystallized from methanol/petroleum ether to yield DMT (3.76 g,

4760
B. Barton et al. / Tetrahedron 74 (2018) 4754e4760
ꢁ
ꢁ
8
.27 mmol, 65%), mp 124e126 C (lit. [21], mp 125e126 C);
[2] T. Hasell, A.I. Cooper, Nat. Rev. Mater. 1 (2016) 16053.
[3] R. Kuhn, F. Stoecklin, F. Erni, Chromatographia 33 (1992) 32.
2
3
ꢁ
ꢁ
[
a
]
D
ꢀ154.5 (c. 0.27, CH
2
Cl
2
) {lit. [21], [
a]
D
ꢀ153 (c. 0.8, CHCl
3
)};
[
[
4] M.R. Caira, S.A. Bourne, B. Mzondo, Molecules 22 (2017) 866.
5] I. Pyka, D. Ryvlin, S. R.t Waldvogel, Compounds, ChemPlusChem. 81 (2016)
926.
ꢀ
1
n
max(solid)/cm 3576ꢀ3271 (br, OH), 3025 (Ar), 2836 (OꢀCH
3
3
),
),
and 1567 (Ar);
4
addition of D
7
(
(
1
d
H
(CDCl
.44 (2H, s, 2HCOCH ), 4.87 (2H, s, 2CPh
O]), 7.15 (2H, m, Ar), 7.24 (4H, m, Ar), 7.32 (2H, m, Ar),
(CDCl )/ppm 61.0
), 125.9 (Ar), 126.1 (Ar), 126.8
Ar), 127.2 (Ar), 128.0 (Ar), 128.5 (Ar), 144.9 (quaternary Ar) and
45.6 (quaternary Ar). (See Supplementary data, Figs. 3S and 4S).
3 H 3
)/ppm d (CDCl )/ppm 2.59 (6H, s, 2OCH
[
[
6] L. Szente, J. Szejtli, Trends Food Sci. Technol. 15 (2004) 137.
7] L.R. Sousa, G. Sogah, D.H. Hoffman, D.J. Cram, J. Am. Chem. Soc. 100 (1978)
3
2
OH [disappears upon
2
4569.
.46 (4H, m, Ar) and 7.63 (8H, m, ortho-Ar);
d
C
3
[8] C.C. Bai, B.R. Tian, T. Zhao, Q. Huang, Z.Z. Wang, Molecules 22 (2017) 1475.
[9] H. Lee, J.-w. Lee, J. Park, Y.-T. Seo, H. Zeng, I.L. Moudrakovski, C.I. Ratcliffe,
OCH ), 80.1 (CPh OH), 85.3 (HCOCH
3
2
3
J.A. Ripmeester, Nature 434 (2005) 743.
10] B. Barton, E.C. Hosten, P.L. Pohl, Tetrahedron 72 (2016) 8099.
[11] B. Barton, E.C. Hosten, P.L. Pohl, Aust. J. Chem. 71 (2018) 133.
[
[
[
12] A. Seayad, M. Ahmed, H. Klein, R. Jackstell, T. Gross, M. Beller, Science 297
2002) 1676.
(
Acknowledgements
13] I.I. Ivanova, E.B. Pomakhina, A.I. Rebrov, M. Hunger, Y.G. Kolyagin,
J. Weitkamp, J. Catal. 203 (2001) 375.
[
[
14] B. Barton, S.-L. Dorfling, E.C. Hosten, P.L. Pohl, Tetrahedron 74 (2018) 2754.
15] B. Barton, M.R. Caira, E.C. Hosten, C.W. McCleland, Tetrahedron 69 (2013)
Financial support is acknowledged from Nelson Mandela Uni-
versity and the National Research Foundation (NRF).
8713.
[16] A. Bruker, APEX2, SAINT and SADABS, Bruker AXS Inc., Madison, WI, 2007.
Appendix A. Supplementary data
[17] G.M. Sheldrick, Acta Crystallogr. A 71 (2015) 3.
[
[
[
18] G.M. Sheldrick, Acta Crystallogr. C 71 (2015) 3.
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20] Z. Shan, X. Hu, Y. Zhou, X. Peng, Z. Li, Helv. Chim. Acta 93 (2010) 497.
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2018.07.044.
[21] F. Toda, K. Tanaka, Z. Stein, I. Goldberg, J. Chem. Soc., Perkin Trans. 2 (1993)
359.
2
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