Rapid access to C3- and Cs-symmetric AAT organogelators via ring opening of a common benzotrifuranone precursor

Article abstract of DOI:10.1080/10610278.2010.500733

Presented is a rapid and general approach to functionalised 1-aza-adamantanetrione (AAT) donor-σ-acceptor molecules from a phloroglucinol-derived trilactone, benzotrifuranone (BTF). Ten C ₃-symmetric AATs bearing diverse aryl amide substituents

Full text of DOI:10.1080/10610278.2010.500733

This article was downloaded by: [University of Ottawa]
On: 18 August 2014, At: 02:17
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Supramolecular Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gsch20
Rapid access to C 3- and C s-symmetric AAT
organogelators via ring opening of a common
benzotrifuranone precursor
Matthew B. Baker a , Ling Yuan a , Christopher J. Marth a , Yan Li a & Ronald K. Castellano a
a Department of Chemistry , University of Florida , P.O. Box 117200, Gainesville, FL,
32611-7200, USA
Published online: 05 Aug 2010.
To cite this article: Matthew B. Baker , Ling Yuan , Christopher J. Marth , Yan Li & Ronald K. Castellano (2010) Rapid access
to C 3- and C s-symmetric AAT organogelators via ring opening of a common benzotrifuranone precursor, Supramolecular
Chemistry, 22:11-12, 789-802, DOI: 10.1080/10610278.2010.500733
To link to this article: http://dx.doi.org/10.1080/10610278.2010.500733
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Supramolecular Chemistry
Vol. 22, Nos. 11–12, November–December 2010, 789–802
Rapid access to C3- and Cs-symmetric AAT organogelators via ring opening of a common
benzotrifuranone precursor†
Matthew B. Baker, Ling Yuan, Christopher J. Marth, Yan Li and Ronald K. Castellano*
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, FL 32611-7200, USA
(Received 21 May 2010; final version received 9 June 2010)
Presented is a rapid and general approach to functionalised 1-aza-adamantanetrione (AAT) donor-s-acceptor molecules
from a phloroglucinol-derived trilactone, benzotrifuranone (BTF). Ten C3-symmetric AATs bearing diverse aryl amide
substituents are accessed in two synthetic steps: (1) the exhaustive ring opening of BTF with aromatic amine nucleophiles
(performed in up to 91% yield) and (2) cyclisation with hexamethylenetetramine (performed in up to 75% yield).
Additionally, stepwise ring opening of BTF allows synthesis of phloroglucinol intermediates with two unique aryl amide
substituents and ultimately Cs-symmetric AATs. Of the novel AATs prepared, three (including the Cs-symmetric hybrid) are
effective gelators of chlorinated solvents (critical gelation concentration (CGC) ¼ 0.2–0.4 wt%) and one, with naphthyl
substituents, forms translucent gels from aromatic solvents (CGC , 0.3 wt%). The combination of AATs with moderately
electron-poor and electron-rich aromatic substituents results in functional complementarity and gelation at concentrations
below what is required for the individual components. Electron microscopy of the gel morphologies shows high aspect ratio
fibres underlying the gel network superstructures in most cases. Polarised optical microscopy has allowed imaging of
representative native organogel phases, and reveals striking morphology differences between gels that also share different
optical and/or thermal stability properties.
Keywords: donor–acceptor molecules; gels; self-assembly; symmetry; through-bond interactions
Introduction
to gelate organic solvents (12, 13) at low concentrations
(,1 wt%). Complementary theoretical studies have
additionally explored the propensity for AATs to self-
assemble in a 1-D head-to-tail manner (16, 17) and found
that the process is accompanied by a decrease in the
HOMO–LUMO gap through the emergence of a unique
supramolecular electronic structure.
1-Aza-adamantanetriones (1, 2) (AATs, Figure 1), with
their tricyclic b-aminoketone (3) cores, are unique
scaffolds that have enabled studies of through-bond (4, 5)
(hyperconjugative (6–8)) interactions at both the molecu-
lar (1, 9–11) and supramolecular level (12, 13). The
rigidity of the core maintains orbital overlap and
communication between the donor (amine) and acceptor
(carbonyls) through the intervening CZC s-bonds (D-s-A
interactions). Previously shown with alkyl- (R ¼ alkyl) and
ester- (R ¼ CH2CO2R’) functionalised AATs, molecular-
level consequences of D-s-A interactions include
decreased basicity of the bridgehead nitrogen (9), bond
length alteration as well as the presence of an uncharacter-
istically strong s-coupled UVabsorption (1). Furthermore,
as the AAT core bears a significant dipole along its C3 axis
and can be functionalised through organic synthesis, this
class of compounds appears attractive for dipole-directed
assembly (14, 15) and supramolecular materials construc-
tion. Accordingly, several aryl (R ¼ CH2Ar) and aryl
amide (R ¼ CH2CONHAr) derivatives have been shown
While computation has implicated assemblies of the
AATs as potentially unique low-band gap supramolecular
architectures (16), rapid access to diversely substituted
targets to facilitate requisite structure-assembly studies has
remained elusive. The previous synthetic approach to aryl
amide functionalised AATs 1, e.g. involved construction of
a protected C3-symmetric phloroglucinol substrate 2, BBr3
deprotection to afford the phloroglucinol 4 and subsequent
cyclisation with hexamethylenetetramine (HMTA)
(Figure 2) (1, 12, 13). Two relatively simple aryl amide
AATs have been prepared in this way (1a and 1b, Table 1),
(12) but the demanding and late-stage deprotection step
has limited access to a structurally diverse family of
compounds. A straightforward solution is presented here,
*Corresponding author. Email: castellano@chem.ufl.edu
†Dedicated to the memory of Prof. Dmitry M. Rudkevich.
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2010 Taylor & Francis
DOI: 10.1080/10610278.2010.500733
http://www.informaworld.com

790
M.B. Baker et al.
6, chemistry made possible by the ‘electronic coupling’ of
N
the lactone rings through its aromatic core. Subsequent
ring opening with a second aniline (H2NAr1) and
cyclisation affords non-C3-symmetric AATs capable of
displaying hybrid structures and functions.
OH
R
N
N
N
N
R
R
O
(HMTA)
R
R
O
HO
OH
Alcohol
O
R
AAT
Results and discussion
Figure 1. Synthesis of the AAT scaffold from a phloroglucinol
precursor.
Synthesis of C3-symmetric AATs (3 ! 1)
The general reaction scheme for C3-symmetric AAT
formation from BTF is shown in Figure 2. BTF (3) was
synthesised on a multi-gram scale according to recently
published methods (18). As shown in Table 1, a variety of
electron-rich and -deficient anilines could be used to open
the lactone rings of 3, providing rapid access to
phloroglucinol substrates for cyclisation into AATs. As a
general procedure, BTF was simply stirred with an excess
of nucleophile in an aprotic solvent at temperatures
ranging from 60 to 1108C (excess (unreacted) aniline
could be recovered through selective extraction and
subsequent purification). Anilines in entries i, v, vii and
viii were able to fully react with 3 in toluene at reflux, with
the exhaustively ring-opened species (4a, e, g and h,
respectively) precipitating from solution as the major
product in good yield (30–80%). Although 3,5-dimetho-
xyaniline is considered a good nucleophile, compound 4d
(entry iv) was only formed in appreciable yield after
several nights of heating (now in THF at reflux), due to the
insolubility of a partially ring-opened (diamide mono-
lactone) intermediate (i.e. 5 in Figure 2). Several other
entries (ii, vi and x) required the slightly more polar THF to
made possible by the recent development of a phloroglu-
cinol-derived trilactone, benzotrifuranone (BTF) 3
(Figure 2) (18).
First shown is the synthesis of (otherwise inaccessible)
C3-symmetric phloroglucinol derivatives that are sub-
strates for cyclisation into the corresponding triamide
AATs, available in one step through nucleophilic ring
opening of BTF’s three lactone rings (Figure 2). This
synthetic approach allows rapid preparation of AAT
targets with increased structural diversity (e.g. bearing
electron-rich, electron-deficient and expanded aromatic
substituents) and, for the first time, demonstration of how
complementary aromatic interactions (19–22) can
enhance AAT assembly in the context of mixed gels
(23, 24). Second is a BTF-based approach to efficiently
prepare the first functionalised AATs of lower (Cs-)
symmetry (i.e. AATs bearing two different types of aryl
amide substituents). Desymmetrisation commences with
stepwise ring opening of 3 to afford (depending on the
reaction conditions) primarily monolactone 5 or dilactone
OMe
OH
ArHN
NHAr
ArHN
NHAr
O
O
N
Ar
BBr3
Ar
HMTA
O
N
N
O
O
O
O
H
H
i-PrOH,
reflux
MeO
OMe
HO
OH
O
O
O
O
O
NHAr
NHAr
NH
1
Ar
2
4
O
O
O
O
OH
Ar1
Ar
O
O
ArHN
ArHN
NHAr1
N
Ar1
H2N
H2N
Ar
HMTA
O
O
N
H
N
H
O
O
HO
O
DMF, ∆
O
Various
conditions
i-PrOH,
reflux
HO
OH
O
OH
O
O
O
O
O
O
NHAr
O
NHAr
NH
3 (BTF)
Ar
5
OH
O
Ar1
O
O
N
Ar1
ArHN
ArHN
NHAr1
H2N
Ar
HMTA
O
N
H
N
H
THF, ∆
O
O
HO
O
i-PrOH,
reflux
HO
OH
O
O
O
O
O
O
NHAr1
NH
6
Ar1
Figure 2. Ring opening of BTF (3) to form phloroglucinol derivatives (4) provides a much milder route to aryl amide AATs (1) than
previous (1, 12) BBr3 deprotection procedures (Ar ¼ aryl), and opportunities to rationally prepare non-C3-symmetric derivatives.
HMTA ¼ hexamethylenetetramine.

Supramolecular Chemistry
791
Table 1. Representative library of C3-symmetric AAT derivatives synthesised in two steps from BTF 3.
Entry
Nucleophile (NH2Ar)
Yield (4)
Yield (1)
Entry
Nucleophile
Yield (4)
Yield (1)
F
i
78% a (4a)
75% b (1a)
vii
76% a (4g)
35% b (1g)
H2N
H2N
O
C12H25
OMe
ii
56% c (4b)
78% c (4c)
61% b (1b)
53% b (1c)
viii
ix
68% a (4h)
55% d (4i)
21% b (1h)
66% b (1i)
H2N
H2N
OMe
iii
H2N
H2N
OMe
C12H25
iv
42% c (4d)
33% a (4e)
91% c (4f)
11% b (1d)
53% b (1e)
40% b (1f)
x
25% c (4j)
36% c (4k)
40% c (4l)
65% b (1j)
H2N
OMe
OMe
H2N
H2N
H2N
OMe
e
v
xi
xii
–
CN
H2N
O
O
e
vi
–
NO2
H2N
a 9 equiv of nucleophile and 1 equiv of BTF in toluene at reflux 16–48 h.
b corresponding phloroglucinol substrate and 1.5–3 equiv of HMTA in i-PrOH at reflux 16–120 h.
c 9 equiv of nucleophile and 1 equiv of BTF in THF at reflux 16–72 h.
d 6 equiv of nucleophile and 1 equiv of BTF in DMF 1208C 24 h.
e no reaction after 5 days.
realise complete conversion, including anilines featuring
more electron-deficient substituents (entries xi and xii).
Phloroglucinols bearing electron-deficient aromatics (4g,
h, k, l) tended to form fairly insoluble materials, attributed
to the increased hydrogen bonding of the amide unit along
with the stronger p-stacking interactions expected for the
less electron-rich aromatic rings (22, 25). Surprisingly, the
use of DMF as a solvent led to incomplete conversion in
most cases, and difficulty in the purification of the
phloroglucinol targets. It is important to recognise that
species 4c–f, h, k and l were hitherto inaccessible from
intermediate 2 (Figure 2).
equivalents of HMTA over 1–5 nights (compounds 4b, h, i
and j needed longer reaction times due to poor solubility of
the phloroglucinol); the corresponding insoluble AATs were
simply collected by filtration and then washed.
Rapid access to diversely functionalised phlorogluci-
nol substrates from BTF has shed new light on the scope of
the AAT-forming cyclisation step (i.e. the conversion of 4
to 1). While broadly functional group tolerant, at least two
classes of phloroglucinols (4) do not react well. Those
bearing quite electron-deficient aromatics (e.g. 4k and 4l)
show no evidence (by 1H NMR analysis) of AAT
formation under the standard conditions even over 5
nights. The result is best explained by the significant
insolubility (due to the forces identified above) of the
substrates. Not implicated is the re-lactonisation of the
phloroglucinol substrates under the HMTA cyclisation
The phloroglucinol derivatives 4a–j were then sub-
jected to standard AAT-forming cyclisation conditions (1, 2,
12, 13). As a general procedure, the phloroglucinol substrate
was stirred in i-PrOH at reflux in the presence of 1.5–3

792
M.B. Baker et al.
O
O
O
O
O
O
H2N
15 equiv
H
H
N
N
O
+
O
O
O
DMF, 40°C
HO
OH
O
HO
O
O
8 h
O
O
HN
3
5
6
30%
5%
56%
O
O
O
O
O
O
H2N
H
H
N
N
O
2.2 equiv
+
O
O
O
THF, 70°C
HO
OH
O
HO
O
O
16 h
O
O
HN
5
3
6
0%
45%
30%
Figure 3. Controlled ring opening of BTF with aniline (yields shown are isolated yields).
conditions, although preliminary evidence does show that
this can occur rapidly under acidic conditions (e.g.
trifluoroacetic acid/toluene). Also unsuitable for AAT
formation are phloroglucinol derivatives with aromatics
bearing long alkoxy chains (e.g. OC12H25, not shown in
Table 1). The negative results demonstrate the delicate
balance between the solubility of the phloroglucinol
starting material and insolubility of the AAT product that
dictates cyclisation success. Given that the formation of
the AAT core occurs at the expense of phloroglucinol
aromaticity, precipitation of the product represents a
potential driving force for the reaction. Further investi-
gation into the scope of the HMTA cyclisation is currently
underway, aided by the methodology outlined in this
manuscript.
Alluded to earlier, electronic ‘communication’
between the three lactone rings of BTF 3 via its central
aromatic core could be the basis for a controllable stepwise
ring opening strategy to form lower-symmetry phloroglu-
cinol derivatives. The nature of the ‘communication’ is
presumably largely inductive, but could more subtly
involve ring strain and p-conjugation effects that would
accompany trace amounts of enol or enolate forms (18).
Although the physicochemical details are still very much
under investigation, the hypothesis seems plausible given
the preliminary results using 3 and aniline (Figure 3). The
synthesis of dilactone 6 can be realised in 56% yield (86%
based on recovered starting material) using an excess of
aniline, mild heating (408C) and a limited reaction time
(8 h). The result demonstrates a relatively rapid initial ring
opening of BTF in the presence of nucleophiles.
Monolactone 5 could be prepared in good yield (45%)
using slightly warmer temperatures and a small excess of
aniline.
Synthesis of Cs-symmetric AATs
Differentially functionalised molecular scaffolds can lead
to unique hybrid properties and multifunctional materials
(26). Traditionally, access to molecules of lower symmetry
is realised via a statistical approach from symmetrical
precursors (often plagued by low yields and difficult
separations), sequential couplings followed by cyclisation
(popular in peptides and porphryins) (27–30) or selective
protection/deprotection (generally plagued by low yields
and poor atom economy) (31, 32). In rare cases, best
characterised by triazine derivatives, (33) the chemical
properties of the core allow for desymmetrisation with
careful control of reaction conditions.
Both monolactone 5 and dilactone 6 were then used to
prepare Cs-symmetric AAT molecules as shown in
Figure 4. Dilactone 6 was opened with an excess of
4-dodecylaniline in hot THF to afford phloroglucinol 4m
that could be isolated by simple filtration; cyclisation of
4m then led to a 56% yield of AAT 1m. Correspondingly,
monolactone 5 could be ring opened in hot DMF by
b-naphthylamine to provide phloroglucinol 4n in good
yield (70%). Subsequent cyclisation with HMTA gave Cs-
symmetric AAT 1n, one of the two possible hybrid
structures of AATs 1a and 1i.

Supramolecular Chemistry
793
C12H25
O
N
OH
O
C12H25
H
N
H
N
H
N
N
O
O
O
N
N
H2N
N
N
N
H
O
O
O
H
THF, reflux, overnight
59%
HO
OH
C12H25
i-PrOH, reflux,
24 h
HO
O
O
O
O
O
O
56%
NH
HN
C12H25
6
4m
1m
C12H25
O
N
O
OH
H
N
H
N
H
N
N
N
N
O
O
O
H2N
N
N
N
H
O
O
O
DMF, 120°C, 12 h
HO
OH
O
i-PrOH, reflux,
24 h
H
HO
OH
O
O
O
O
70%
41%
NH
HN
HN
5
4n
1n
Figure 4. Utilisation of 5 and 6 for the synthesis of Cs-symmetric AAT molecules.
Characterisation of supramolecular assemblies
dissemination of the gel phase to a viscous suspension of
the material. This behaviour contrasts with that of a 0.3
wt% (translucent) gel of 1j in toluene (Tgel ¼ 728C).
Cooling after melting of the 1j gel results in a semi-gel
C3-symmetric derivatives
Given that previously prepared 1b showed surprising self-
assembly behaviour in solution and the ability to gelate
organic solvents, (12) the newly synthesised AAT
derivatives were tested for analogous behaviour in a
representative selection of organic solvents (see Table S1
in the Supporting Information for full profile). The
majority of the derivatives synthesised were exceedingly
insoluble in most solvents, aside from DMF, DMSO and
pyridine, a trend found for other AATs. Among the
structures given in Table 1, compounds 1e, g and j form
gels (as defined by the inverted vial technique (34–36)) in
a limited range of solvents upon heating (to form an
isotropic phase) and cooling at ambient temperature
(Figure 5). AAT 1e form an opaque gelatinous phase in
CHCl3 (Figure 5(A)) from 0.25–2 wt%, AAT 1g forms an
opaque gel in 1,1,2,2-tetrachloroethane (TCE; Figure 5(B))
from 0.25–1 wt% and AAT 1j forms translucent gels in
both toluene (Figure 5(C)) and benzene (not shown) from
0.2–3 wt%. It is worth noting that these gel phases show
no evidence of dissemination over the course of several
weeks.
By utilising the ‘dropping-ball’ method, (37) the Tgel
of a 0.3 wt% solution of 1g in TCE was measured to be
1108C – the most thermally stable gel for this class of
compounds to date – while the Tgel of a 0.3 wt% solution
of 1e in CHCl3 was determined to be 458C. The sol-gel
transition probed in the preceding experiments was not
wholly reversible; once melted, the mixture does not return
to the gel state upon cooling, but must be heated to an
isotropic mixture and allowed to cool again (a process that
may be repeated multiple times). Unexpected given the
high thermal stability exhibited by these gels, moderate
shock to the formed gel resulted in an immediate
Figure 5. Inverted gels formed in sealed glass vials. (A) 0.30
wt% compound 1e in CHCl3, (B) 0.30 wt% compound 1g in
TCE, (C) 0.20 wt% compound 1j in toluene, (D) 0.30 wt% of an
equimolar 1e and 1g in TCE, (E) 0.25 wt% equimolar amounts of
1e and 1g in a 2:1 mixture of CHCl3: TCE and (F) 0.40 wt%
compound 1m in CHCl3.

794
M.B. Baker et al.
(unable to support its own weight, but gelatinous), while
agitation also results in a semi-gel.
Rapid access from BTF 3 to aryl amide AAT
derivatives 1 with diverse aromatic substituents has
encouraged the exploration of mixed AAT assemblies for
the first time. This line of investigation is relatively new,
but is already showing a role for complementary aromatic
interactions in the self-assembly and gel-forming beha-
viour of the molecules. An equimolar (binary) mixture of
1e and 1g, e.g. forms a gel in both neat TCE (critical
gelation concentration (CGC) ¼ 0.3 wt% and
Tgel ¼ 558C) and a 1:2 (w/w) TCE:CHCl3 (CGC ¼ 0.2
wt%) solution (Figures 5(D) and (E)). Of note here is that
compound 1g is unable to gel TCE below a concentration
of 0.25 wt% and that compound 1e is freely soluble in TCE
up to 2 wt%, yet the combination of the two enables
gelation of the solvent system. While little can be inferred
with respect to molecular level ordering from this result, it
does suggest that there is some complementarity between
the molecules in the gel network. The ability to form
mixed gels within a system unlocks the possibility for
tailorability of gel morphologies and properties; this
approach has already proven promising for mixed gels
with H-bonding motifs (23, 38).
Samples of gels 1e and g were freeze-dried
(lyophilised) for imaging of the underlying morphology
that could form the basis for gel networks. As is evident in
the TEM micrographs (Figures 6(A)–(D)), all samples
show the presence of high aspect ratio fibres common to
many organogelators (36, 39–41). Fibres here can be in
the order of millimetres in length, and consist of bundles
(4–10) of sheets with the individual sheets averaging
200 nm in width. The fibres in the micrographs appear
brittle, with fracturing and splintering of the structures at
the extremes. The overall morphology contrasts with
previously studied 1b that mostly showed lamellar
architectures on the nanoscale (12).
Figure 6. Micrographs of dried gels. TEM images of (A) high
aspect ratio fibres formed in the freeze-dried gel of 1e, nanoscale
features within the fibres formed in the freeze-dried gel of 1e (B)
and 1g (C); (D) fibrous aggregates formed within the mixed gel of
1e and 1g. (E) and (F): SEM images of the entangled fibre
networks formed in the CPD gel sample of 1j.
To gain better insight into the morphology of the
toluene gel of 1j, scanning electron microscopy (SEM)
was used to image critical point dried (CPD) gel samples
(42). In the CPD gel sample of 1j, a lamellar sheet
architecture was observed with layers of uniform thickness
of about 5 mm (Figures 6(E) and (F)). The surface of the
sheets reveals ,3 mm entangled fibres, and smaller fibres
are observed among the entangled fibres that comprise the
self-assembled network. Both fibrous and lamellar
architectures have been observed earlier in the AAT
systems, but this is the first case where both morphologies
are visible in one sample.
native gels can be imaged, albeit with lower resolution, by
polarised optical microscopy (POM). The gels of 1e in
CHCl3 and 1g in TCE have been studied in this way
to reveal features that are not present in the TEM
micrographs (Figure 7). While the former shows a fairly
uniform distribution of crystalline (birefringent) fibres, the
latter shows a dual morphology. Evident in the micrograph
of 1g is spherulitic crystal growth, usually detrimental to
1-D fibrous gel formation (43); however, closer inspection
also shows the presence of extremely high aspect ratio
fibres dispersed throughout the sample. The longer fibres
are only weakly birefringent at their edges. Quick cooling
of a solution of 1g in TCE leads to the formation of mostly
well-dispersed crystalline fibres (not shown), and no gel
formation. It is hypothesised that the dual morphology of
the gel formed from 1g at room temperature imparts the
impressive thermal stability to this system (vida supra).
While TEM and SEM techniques provide insightful
nanoscale images, not necessarily observed are the
architectures that best reflect the assemblies that constitute
the native organogel phase (i.e. often observed are
assemblies formed upon solvent evaporation that survive
the freeze drying or CPD process). Structures within the

Supramolecular Chemistry
795
Figure 7. POM images of the native gel phases (top row is 1e in CHCl3; bottom row is 1g in TCE; the images on the right side have been
taken with the polarisers crossed). Notice the distinctly different morphologies found in the two systems.
Cs-symmetric derivatives
Conclusions
Cs-symmetric 1n shows no evidence of gelation of the
solvents tested, a result consistent with its poor solubility
and lack of gelation of its AAT congeners 1a and 1i.
Hybrid 1m does, however, gel in CHCl3 quite efficiently
(Figure 5(F)). The gel’s transparency and parameters
(CGC , 0.4 wt% and Tgel , 508C) are similar to proper-
ties previously reported for C3-symmetric 1b (CGC , 0.5
wt% and Tgel , 578C), but obviously quite unique from
non-gelator 1a. Also, akin to transparent gels 1b and 1j,
the 1m gel is quite resistant to shock and maintains its
shape under mild agitation.
New approaches to the synthesis of fully substituted
phloroglucinols (4) from a common BTF, 3, precursor have
provided efficient access to previously unattainable C3- and
Cs-symmetric AATs (1). The synthetic chemistry has
enabled preparation of a structurally diverse 10-component
library of C3-symmetric aryl amide AATs, and exploration
of the first binary AAT-based organogel systems. Enhanced
gelation has been observed for ensembles containing AAT
monomers with electronically complementary aromatic
substituents (1e and g). Introduction of an expanded
aromatic substituent to the AAT scaffold has provided a
molecule (1j) that effectively immobilises aromatic
solvents at low concentrations (,0.3 wt%). Quite uniquely,
BTF also enables a stepwise approach to prepare the first
differentially functionalised phloroglucinol derivatives and
ultimately Cs-symmetric AAT molecules; one derivative,
1n, forms translucent gels at , 0.4 wt% in chloroform.
This discovery bodes well for the construction of chimeric
AAT molecules for structure-property elucidation and
creation of hybrid functional materials.
It is anticipated that access to lower symmetry and
hybrid AATs will provide a unique way to identify the
structural elements most responsible for the gelation
properties of this molecular class, and even an approach
to rationally tune macromolecular properties. Established
thus far is that AAT compounds with long alkyl chains
on the periphery form more optically clear and
mechanically stable gels, while the simple aryl (13) or
aryl amide AAT derivatives form highly crystalline
networks that are able to immobilise solvent. Current
investigation into the rheology of AAT gels should begin
to draw connections between the bulk properties,
observed morphologies and molecular structures of the
systems.
The organogels derived from both the C3- and Cs-
symmetric AAT systems have been characterised both
macroscopically and on the nanoscale. Electron microscopy
of the gel morphologies shows high aspect ratio fibres
underlying the gel network superstructures in most cases.

796
M.B. Baker et al.
POM has allowed imaging of the native organogel phases,
and revealed striking morphology differences between gels
that also share different optical and/or phase stability
properties. Overall, access to a broader array of AATs is
beginning to draw previously inaccessible relationships
between structure, solubility and gel appearance/stability
within this class of self-assembling molecules. Among the
most alluring future lines of investigation with the AATs is
their exploration in the context of supramolecular
electronics (44). Efforts here will surely be leveraged by
the BTF methodology that can provide molecular and
supramolecular AAT structures rapidly.
had aged for 12 h at 258C, a steel ball with a diameter of
2 mm was placed on top of the gel, the vial was resealed and
placed in an oil bath. The temperature was slowly increased
(ca. 0.58C/min), and monitored using a thermometer
submerged in a vial containing an equal weight of neat TCE
also in the oil bath, while observing the position of the steel
ball. The temperature at which the ball touched the bottom
of the vial was taken as the Tgel temperature. This
experiment was carried out thrice and the Tgel temperatures
obtained were reproducible to within ^28C.
Representative gel freeze drying procedure
A vial containing the organogel of 1g in TCE was frozen in
liquid nitrogen and transferred to a freeze dry system
(Labconco FreeZone 4.5 L) overnight.
Experimental
General
Reagents and solvents were purchased from Acros, Aldrich
or Fluka, and used without further purification unless
otherwise specified; 2-naphthylamine was purchased from
Toronto Research Chemicals Inc. THF and DMF were
degassed in 20-l drums and passed through two sequential
purification columns (molecular sieves) under a positive
argon atmosphere using a custom Glass Contour solvent
system (Glass Contour Inc., Laguna Beach, CA, USA). Thin
layer chromatography (TLC) was performed on Dynamic
Adsorbents, Inc. aluminium-backed TLC plates with
CPD of 1f gels
Supercritical fluid drying of 1f gels was performed in a
3000 psi rated vessel (Parr Instruments). Samples were
placed into regenerated cellulose dialysis bags with a pore
diameter of 12000–14000 MWCO (Fisher Scientific,
Pittsburgh, PA, USA). The samples were placed inside the
drying chamber and liquid CO2 was introduced. Toluene
was exchanged with liquid CO2 over 5–6 solvent
exchange steps. After complete solvent removal, the
vessel containing liquid CO2 was heated via a water jacket
and water bath to 508C and 1500 psi. At equilibrium, the
supercritical CO2 was released from the vessel at a rate no
greater than 4 l/min.
1
visualisation via UV light or staining. H NMR and 13C
NMR spectra were recorded on a Varian Mercury 300,
Gemini 300 or an Inova 500 spectrometer. Chemical shifts
(d) are given in parts per million (ppm) relative to residual
protonated solvent (CHCl3: dH 7.27ppm, dC 77.00 ppm;
DMSO: dH 2.50ppm, dC 39.50 ppm; pyridine: dH 7.22, 7.58,
8.74ppm; dC 123.9, 135.9, 150.4 ppm). Abbreviations used
are s (singlet), d (doublet), t (triplet), q (quartet) and m
(multiplet). MS spectra (HR-MS) were acquired on a Bruker
APEX II 4.7 T Fourier Transform Ion Cyclone Resonance
mass spectrometer (Bruker Daltonics, Billerica, MA, USA).
DSC and TGA thermograms were taken on a Thermal
Analysis DSC Q1000 and TGA Q5000, respectively. POM
images were recorded by a Leica DFC295 camera using a
Leica DMLP microscope coupled with a Linkham LTS350
heating stage.
Dried gel analysis by TEM
Some of the dried gel was flaked onto a Formvar/Carbon
200 mesh copper grid (Ted Pella Inc., Redding, CA, USA).
The sample was then imaged on a JEOL TEM 200CX.
Dried gel analysis by SEM
For all SEM experiments, a JEOL JSM 6400 scanning
electron microscope was used. Samples were adhered to
SEM stubs using conductive copper tape, and then
sputtered with Au/Pd to improve the resolution of the
images. The sputtering current was 45 mA, the Ar pressure
was 75 mTorr and the sputtering time was 60 s. This
yielded an Au/Pd film that was , 16 nm thick. The SEM
measurements were performed at 15 kV.
Representative gel formation
AAT 1g (5.1 mg, 0.3% by weight) and 1,1,2,2-tetrachlor-
oethane (TCE, 1.71 g) were combined in a sealed vial. The
vial was then heated with a heat gun until a homogeneous
solution was formed. The vial was then allowed to
gradually cool to room temperature on the bench top,
during which time the gel rapidly formed (ca. 10 min).
Synthesis
Representative synthesis of phloroglucinols from BTF:
synthesis of 2,20,200-(2,4,6-trihydroxybenzene-1,3,5-
triyl)tris(N-(3,4-dimethoxyphenyl)acetamide) (4e)
Representative Tgel determination
An organogel of 1g in TCE with a volume of ca. 2.0 ml was
prepared in a vial with a diameter of 10 mm. After the gel
To a 25-ml round-bottomed flask equipped with stirbar
and reflux condenser were added, BTF 3 (250 mg,

Supramolecular Chemistry
797
1.02 mmol) and 4-aminoveratrole (1.40 g, 9.14 mmol),
followed by degassed toluene (10 ml). The reaction vessel
was placed in an oil bath and heated to reflux overnight
under an argon atmosphere. The solution was then cooled
to room temperature and the precipitates were removed by
filtration and subsequently washed with toluene, ethyl
acetate and hexanes. Compound 4e (240 mg, 33%) was
obtained as a light brown solid and used without further
filtration and subsequent washing yielded 4c (152 mg,
1
78% yield) as a white powder. H NMR (d6-DMSO): d
3.70 (m, 15H), 6.87 (d, J ¼ 8.9 Hz, 6H), 7.50
(d, J ¼ 8.9 Hz, 6H), 9.64 (s, 3H), 10.14 (s, 3H). 13C
NMR (d6-DMSO): 32.20, 55.13, 103.41, 113.82, 121.09,
131.83, 153.69, 155.42, 171.42. HR-MS (ESI): calculated
for C33H34N3O9 [M þ H]þ 616.2290, found 616.2283.
1
purification. H NMR (d6-DMSO): d 3.70 (m, 24H), 6.88
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(3,5-
dimethoxyphenyl)acetamide) (4d)
(d, J ¼ 8.8 Hz, 3H), 7.09 (dd, J ¼ 8.7, 2.2 Hz, 3H), 7.32 (d,
J ¼ 2.2 Hz, 3H), 9.53 (s, 3H), 10.12 (s, 3H). 13C NMR
(d6-DMSO): d 32.25, 55.31, 55.66, 103.38, 104.60,
111.39, 111.94, 132.33, 144.99, 148.46, 153.64, 171.35.
HR-MS (ESI): calculated for C36H40N3O12 [M þ H]þ
706.2607, found 706.2608.
BTF (150 mg, 0.62 mmol) and 3,5-dimethoxyaniline
(1.16 g, 7.57 mmol) were heated to reflux overnight in
THF (4 ml). After cooling to room temperature, the
precipitates were removed by filtration and subsequently
washed with EtOAc and hexanes. Further isolation of
product from the filtrate was possible by column
chromatography with a 5% MeOH:DCM eluent. The
products from both purification methods were combined to
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-
phenylacetamide) (4a)
1
The compound was synthesised starting from BTF
(150 mg, 0.610 mmol), aniline (283 mg, 3.00 mmol) and
DMF (7 ml). The reaction vessel was heated to 1208C for
15 h. Upon cooling to room temperature, the reaction
mixture was poured into brine and extracted with EtOAc.
The combined organic layers were washed with 1 M HCl
and water, and then dried over Na2SO4. The solvent was
removed and the residue was purified by flash column
chromatography (1/3 to 1/1 EtOAc/hexanes) to yield 4a
(240 mg, 97%). The spectroscopic data match those in the
literature (12). 1H NMR (d6-DMSO): d 3.71 (s, 6H), 7.05
(t, J ¼ 7.5 Hz, 3H), 7.30 (t, J ¼ 7.8 Hz, 6H), 7.61 (d,
J ¼ 7.8 Hz, 6H), 9.32 (s, 3H), 10.21 (s, 3H). 13C NMR (d6-
DMSO): d 32.4, 103.4, 119.3, 123.4, 128.7, 138.9, 153.6,
171.6.
yield 4d (177 mg, 42% yield) as a light brown solid. H
NMR (d6-DMSO): d 3.69 (m, 24H), 6.20 (s, 3H), 6.86
(d, J ¼ 1.9 Hz, 6H), 9.13 (s, 3H), 10.10 (s, 3H). 13C NMR
(d6-DMSO): d 32.41, 55.03, 95.44, 97.51, 103.31, 140.64,
153.55, 160.42, 171.47. HR-MS (ESI): calculated for
C36H40N3O12 [M þ H]þ 669.2555, found 669.2594.
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(2,3-
dihydrobenzo[b][1,4]dioxin-6-yl)acetamide) (4f)
BTF (100 mg, 0.41 mmol) and 2,3-dihydrobenzo[b][1,4]-
dioxin-6-amine (490 mg, 3.2 mmol) were combined in
THF (10 mL) and the reaction vessel was heated to reflux
overnight. After cooling to room temperature, the solvent
was removed in vacuo, and the residue was redissolved in
EtOAc and washed with 0.1 N HCl, deionised (DI) H2O
and then dried over Na2SO4. The remaining solvent was
removed in vacuo to yield 4f (260 mg, 91%) as a brown
solid. 1H NMR (d6-DMSO): d 3.66 (s, 6H), 4.20 (s, 12H),
6.77 (d, J ¼ 8.6 Hz, 3H), 6.98 (dd, J ¼ 8.8 Hz, 2.2 Hz,
3H), 7.22 (d, J ¼ 2.2 Hz, 3H), 9.49 (s, 3H), 10.07 (s, 3H).
13C NMR (d6-DMSO): d 32.23, 63.89, 64.14, 103.38,
108.59, 112.69, 116.73, 132.44, 139.48, 142.86, 153.62,
171.32. HR-MS (ESI): calculated for C36H33N3O12Na
[M þ Na]þ 722.1956, found 722.1947.
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(4-
dodecylphenyl)acetamide) (4b)
BTF (52 mg, 0.21 mmol) was added to a stirred solution of
4-dodecylaniline (405 mg, 1.55 mmol) in THF (5 ml). The
reaction vessel was heated to reflux for 16 h. Precipitates
were removed by filtration and washed with hexanes to
yield 4b (122 mg, 56%) as a white solid. The spectroscopic
data match those in the literature (12). 1H NMR
(d6-DMSO/CDCl3): d 0.83 (t, J ¼ 6.5 Hz, 9H), 1.21 (m,
66H), 3.70 (s, 3H), 7.04 (d, J ¼ 8.5 Hz, 6H), 7.46
(d, J ¼ 8.5 Hz, 6H), 9.71 (s, 3H), 10.11 (s, 3H).
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(4-
fluorophenyl)acetamide) (4g)
BTF (100 mg, 0.41 mmol) and p-fluoroaniline (400 mg,
3.66 mmol) were heated to reflux in toluene (10 ml)
overnight. The solids were removed by filtration and
washed with toluene, EtOAc and hexanes to yield
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(4-
methoxyphenyl)acetamide) (4c)
BTF (78 mg, 0.32 mmol) and p-anisidine (40 mg,
3.2 mmol) were heated to reflux overnight in toluene
(5 ml). Isolation of solids from the reaction mixture by
1
compound 4g (180 mg, 76%) as an off-white powder. H
NMR (d6-DMSO): d 3.69 (s, 6H), 7.14 (t, J ¼ 8.8 Hz, 6H),

798
M.B. Baker et al.
7.62 (dd, J ¼ 8.9, 5.0 Hz, 6H), 9.25 (s, 3H), 10.24 (s, 3H).
13C NMR (d6-DMSO): d 32.23, 103.40, 115.26 (d,
J ¼ 22.6 Hz), 121.11 (d, J ¼ 7.5 Hz), 135.32 (d,
J ¼ 1.3 Hz), 153.63, 158.04 (d, J ¼ 239 Hz), 171.41.
HR-MS (ESI): calculated for C30H28F3N4O6 [M þ NH4]þ
602.1509, found 602.1528.
54H), 1.68 (m, 6H), 2.73 (t, J ¼ 7.2 Hz, 6H), 4.38 (s, 6H),
7.39 (d, J ¼ 8.7 Hz, 3H), 7.89 (m, 15 H), 8.63 (s, 3H),
11.74 (s, 3H). 13C NMR (d5-pyridine): d 14.61, 23.26,
29.93, 30.14, 30.22, 30.27, 32.00, 32.44, 36.52, 105.30,
118.31, 121.61, 123.12, 126.89, 128.33, 128.72, 128.77,
131.77, 133.15, 136.82, 140.25, 155.92, 174.34. HR-MS
(ESI): calculated for C78H105N3O6Na [M þ Na]þ
1202.7901, found 1202.7805.
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(4-
methylesterphenyl)acetamide) (4h)
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(3-
cyanophenyl)acetamide) (4k)
BTF (200 mg, 0.81 mmol) and methyl-4-aminobenzoate
(1.80 g, 12.2 mmol) were heated to reflux in THF (10 ml)
over 2 days. The THF was then removed in vacuo, and the
solids were suspended and sonicated in ethyl acetate, and
isolated by filtration to yield compound 4h (380 mg, 68%)
BTF (200 mg, 0.81 mmol) and 3-aminobenzonitrile
(2.10 g, 17.6 mmol) were heated to reflux in dry, degassed
THF over 3 nights. The reaction precipitates were
removed by filtration and washed with hot EtOAc and
hot i-PrOH to yield 4k (175 mg, 36%) as an off-white
1
as a white powder. H NMR (d6-DMSO): d 3.72 (s, 6H),
3.81 (s, 9H), 7.74 (d, J ¼ 8.8 Hz, 6H), 7.91 (d, J ¼ 8.8 Hz,
6H), 8.85 (s, 3H), 10.42 (s, 3H). 13C NMR (d6-DMSO): d
32.48, 51.86, 103.29, 118.47, 123.79, 130.26, 143.60,
153.57, 165.80, 171.58. HR-MS (ESI): calculated for
C36H34N3O12 [M þ H]þ 700.2137, found 700.2147.
1
powder. H NMR (d6-DMSO): d 3.71 (s, 6H), 7.52 (m,
6H), 7.84 (dt, J ¼ 7.0, 2.1 Hz, 3H), 8.08 (s, 3H), 8.83 (s,
3H), 10.40 (s, 3H). 13C NMR (d6-DMSO): d 32.34, 103.29,
111.53, 118.70, 121.72, 123.64, 126.66, 130.22, 139.97,
153.58, 171.57. HR-MS (ESI): calculated for C33H25N6O6
[M þ H]þ 601.1830, found 601.1825.
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-
(naphthalen-2-yl)acetamide) (4i)
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(3-
nitrophenyl)acetamide) (4l)
BTF (86 mg, 0.35 mmol) was dissolved in DMF (5 ml) and
heated to 608C while sparging the solution with argon.
2-Naphthylamine (450 mg, 3.2 mmol) was added in one
aliquot and the reaction was allowed to stir under argon at
1208C over 2 nights. The reaction mixture was cooled,
poured into EtOAc and washed with 0.1 N HCl, H2O and
brine. The organic layers were dried over Na2SO4 and the
solvent was removed in vacuo. The residue was triturated
with DCM and the insoluble material was removed by
filtration and washed to yield 4i (130 mg, 55%) as a light
BTF (75 mg, 300 mmol) and 3-nitroaniline (630 mg,
4.6 mmol) were heated to reflux in dry, degassed THF
overnight. Precipitates from the reaction mixture were
removed by filtration and washed to yield compound 4l
(80 mg, 40%) as a white powder. 1H NMR (d6-DMSO): d
3.74 (s, 6H), 7.60 (m, 3H), 7.92 (m, 6H), 8.65 (s, 3H), 8.80
(s, 3H), 10.54 (s, 3H). 13C NMR (d6-DMSO): d 32.38,
103.30, 113.17, 117.58, 125.03, 130.13, 140.35, 147.93,
153.60, 171.60. HR-MS (ESI): calculated for
C30H24N6O12Na [M þ Na]þ 683.1344, found 683.1344.
1
tan solid. H NMR (d6-DMSO): d 3.81 (s, 6H), 7.40 (m,
3H), 7.45 (m, 3H), 7.64 (d, J ¼ 8.6 Hz, 3H), 7.79 (d,
J ¼ 8.1 Hz, 3H), 7.83 (d, J ¼ 8.1 Hz, 3H), 7.86 (d,
J ¼ 8.8 Hz, 3H), 8.30 (s, 3H), 9.31 (s, 3H), 10.37 (s, 3H).
13C NMR (d6-DMSO): d 32.45, 103.51, 115.52, 120.05,
124.63, 126.38, 127.30, 127.47, 128.33, 129.78, 133.36,
136.51, 153.68, 171.75. HR-MS (ESI): calculated for
C42H33N3O6Na [M þ Na]þ 698.2262, found 698.2253.
2,20-(2,4,6-Trihydroxy-5-(2-oxo-2-(phenylamino)ethyl)-1,
3-phenylene)bis(N-(4-dodecylphenyl)acetamide) (4m)
To a solution of compound 6 (40 mg, 120 mmol) in THF
(5 ml) was added, 4-dodecylaniline (120 mg, 470 mmol).
The reaction mixture was heated to 708C overnight, after
which the THF was removed in vacuo to yield tan solids.
The crude material was dissolved in hot EtOAc/hexanes
and allowed to slowly precipitate upon cooling. Filtration
and washing with 0.1 N HCl yielded 4m (61 mg, 59%) as a
2,20,200-(2,4,6-Trihydroxybenzene-1,3,5-triyl)tris(N-(7-
dodecyl-naphthalen-2-yl)acetamide) (4j)
BTF (26 mg, 0.11 mmol) and 7-dodecyl-2-aminonaphtha-
lene (290 mg, 0.94 mmol, see Supporting Information for
synthesis) were combined in THF (5 ml) and allowed to
stir at reflux overnight. Upon cooling, precipitates formed
in the reaction mixture were removed by filtration and
1
waxy, off-white solid. H NMR (d6-DMSO): d 0.84 (t,
J ¼ 6.4 Hz, 6H), 1.23 (br s, 36H), 1.52 (m, 4H), 3.70 (br s,
6H), 7.06 (m, 5H), 7.29 (t, J ¼ 7.9 Hz, 2H), 7.48 (d,
J ¼ 8.5 Hz, 4H), 7.60 (d, J ¼ 7.9 Hz, 2H), 9.43 (m, 3H),
10.12 (s, 2H), 10.17 (s, 1H). 13C NMR (d6-DMSO): d
13.94, 22.07, 28.55, 28.68, 28.83, 28.97, 29.00, 30.95,
1
washed to yield 4j (30 mg, 25%) as a white powder. H
NMR (d5-pyridine): d 0.88 (t, J ¼ 6.6 Hz, 9H), 1.32 (m,

Supramolecular Chemistry
799
31.27, 32.31, 34.52, 103.41, 103.49, 119.37, 119.49,
123.38, 128.39, 128.68, 136.43, 137.48, 138.90, 153.65,
171.52. HR-MS (ESI): calculated for C54H76N3O6
[M þ H]þ 862.5729, found 862.5719.
was brought to reflux over 3 nights under argon.
Precipitates formed during the reaction were removed by
filtration and washed, yielding 1c (37 mg, 34%) as a white
1
solid. H NMR (d6-DMSO): d 2.68 (s, 6H), 3.65 (s, 9H),
3.86 (s, 6H), 6.78 (d, J ¼ 8.7 Hz, 6H), 7.39 (d, J ¼ 8.7 Hz,
6H), 9.81 (s, 3H). 13C NMR (d6-DMSO): d 33.55, 55.10,
70.18, 70.31, 113.69, 120.36, 132.54, 154.88, 167.04,
198.32. HR-MS (ESI): calculated for C36H37N4O9
[M þ H]þ 669.2555, found 669.2594.
2,20-(2,4,6-Trihydroxy-5-(2-(naphthalen-2-ylamino)-2-
oxoethyl)-1,3-phenylene)bis(N-phenylacetamide) (4n)
A stirring solution of 5 (86 mg, 0.20 mmol) in DMF (5 ml)
was treated with 2-naphthylamine (34 mg, 0.24 mmol) and
heated to 1208C for 12 h. The solvent was removed in
vacuo and the residue was dissolved in ethyl acetate. The
organic layer was washed with 10% HCl and water.
The combined organic layers were dried with Na2SO4. The
solvent was then removed in vacuo and the crude product
was purified via column chromatography (hexane/EtOAc
1:1) to afford 4n (80 mg, 70%) as a yellow solid. 1H NMR
(d6-DMSO): d 3.73 (s, 4H), 3.78 (s, 2H), 7.05 (t,
J ¼ 7.5 Hz, 2H), 7.30 (t, J ¼ 7.5 Hz, 4H), 7.43 (m, 2H),
7.62 (m, 5H), 7.85 (m, 3H), 8.28 (s, 1H), 9.31 (s, 2H), 9.32
(s, 1H), 10.19 (s, 2H), 10.37 (s, 1H). 13C NMR
(d6-DMSO): d 13.58, 20.26, 31.86, 59.25, 102.94,
105.26, 115.01, 117.88, 118.85, 119.55, 120.32, 122.91,
124.5, 125.33, 125.8, 125.9, 126.82, 126.95, 127.84,
127.96, 128.23, 129.29, 132.87, 134.49, 136.02, 138.41,
146.14, 153.15, 171.09, 171.26. HR-MS (ESI): calculated
for C34H29N3O6Na [M þ Na]þ598.1949, found 598.1944.
2,20,200-((3s,5s,7s)-4,6,10-Trioxo-1-azaadamantane-3,5,7-
triyl)tris(N-(3,5-dimethoxyphenyl)acetamide) (1d)
To i-PrOH (5 ml) was added, 4d (99 mg, 0.14 mmol),
followed by HMTA (56 mg, 0.40 mmol), and the reaction
mixture was heated to reflux for 2 days. After cooling to
room temperature, isolation and washing of the precipi-
tates from the reaction mixture yielded 1d (11 mg, 11%) as
a light orange solid. 1H NMR (d6-DMSO): d 2.74 (s, 6H),
3.68 (s, 18H), 3.92 (s, 6H), 6.16 (s, 3H), 6.79 (d, J ¼ 1 Hz,
6H), 9.98 (s, 3H). 13C NMR (d6-DMSO): d 25.48, 33.79,
55.03, 70.16, 95.09, 97.10, 140.96, 160.41, 167.63,
198.13. HR-MS (ESI): calculated for C36H40N3O12
[M þ H]þ 759.2872, found 759.2877.
2,20,200-((3s,5s,7s)-4,6,10-Trioxo-1-azaadamantane-3,5,7-
triyl)tris(N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acetamide)
(1f)
Representative procedure for the synthesis of AATs from
phloroglucinols:synthesisofN-(3,4-dimethoxyphenyl)-2-(4,
6,10-trioxo-5,7-di-3,4-dimethoxyphenylcarbamoylmethyl-
1-aza-tricyclo[3.3.1.13,7]dec-3-yl)-acetamide (1e)
To a solution of 4f (100 mg, 0.15 mmol) in i-PrOH (5 ml)
was added, HMTA (64 mg, 0.46 mmol) and the reaction
vessel was heated to reflux overnight. Precipitates from the
reaction mixture were removed by filtration, resuspended
in EtOAc and filtered again with washing to yield 1f
(44 mg, 40%) as a light brown solid. 1H NMR (d6-DMSO):
d 2.70 (s, 6H), 3.89 (s, 6H), 4.19 (d, J ¼ 6.5 Hz, 12H), 6.73
(d, J ¼ 8.6 Hz, 3H), 6.92 (dd, J ¼ 8.1 Hz, 2.2 Hz, 3H),
7.15 (d, J ¼ 2.2 Hz, 3H), 9.82 (s, 3H). 13C NMR (d6-
DMSO): d 33.61, 63.88, 64.16, 70.32, 70.15, 107.96,
112.10, 116.60, 133.05, 138.95, 142.84, 167.07, 198.25.
HR-MS (ESI): calculated for C39H37N4O12 [M þ H]þ
753.2403, found 753.2398.
To a 10-ml round-bottomed flask with stirbar and reflux
condenser was added, compound 4e (125 mg, 0.180 mmol)
followed by HMTA (75 mg, 0.53 mmol) and degassed
i-PrOH (4 ml). The reaction vessel was then placed in an
oil bath and allowed to reflux with stirring overnight under
an argon atmosphere. The next day, the reaction vessel was
allowed to cool to room temperature and the precipitates
were removed by filtration and washed with i-PrOH (1 ml).
The solids were then resuspended in ethyl acetate (10 ml),
sonicated and filtered to yield compound 1e (75 mg, 53%)
1
as a slightly tan solid. H NMR (d6-DMSO): d 2.73 (br s,
6H), 3.69 (br s, 18H), 3.93 (br s, 6H), 6.84 (d, J ¼ 8.8 Hz,
3H), 7.01 (dd, J ¼ 8.6, 1.6 Hz, 3H), 7.27 (d, J ¼ 1.6 Hz,
3H), 9.87 (s, 3H). 13C NMR (d6-DMSO): 33.66, 55.35,
55.73, 70.21, 70.37, 104.08, 110.74, 112.06, 133.07,
144.54, 148.49, 167.15, 198.27. HR-MS (ESI): calculated
for C39H43N4O12 [M þ H]þ 759.2872, found 759.2902.
N-(4-Fluorophenyl)-2-(4,6,10-trioxo-5,7-di-4-fluorophenyl
-carbamoylmethyl-1-aza-tricyclo[3.3.1.13,7]dec-3-yl)-
acetamide (1g)
To a solution of 4g (95 mg, 160 mmol) in i-PrOH was
added, HMTA (69 mg, 490 mmol) and the mixture was
heated to reflux overnight. Removal of the solids by
filtration and subsequent washing yielded 1g (33 mg, 35%)
2,20,200-((3s,5s,7s)-4,6,10-Trioxo-1-azaadamantane-3,5,7-
triyl)tris(N-(4-methoxyphenyl)acetamide) (1c)
1
as a white powder. H NMR (d6-DMSO): d 2.76 (s, 6H),
3.92 (s, 6H), 7.10 (t, J ¼ 8.8 Hz, 6H), 7.54 (dd, J ¼ 8.7,
To a solution of 4c (99 mg, 0.16 mmol) in i-PrOH (5 ml)
was added, HMTA (60 mg, 0.43 mmol) and the solution
5.0 Hz, 6H), 10.07 (s, 3H). 13C NMR (d6-DMSO): d 25.48,

800
M.B. Baker et al.
33.61, 70.17, 115.12 (d, J ¼ 22.3 Hz), 120.52 (d,
J ¼ 7.7 Hz), 135.73, 157.71 (d, J ¼ 238 Hz), 167.45,
198.25. HR-MS (DART): calculated for C33H28F3N4O6
[M þ H]þ 633.1961, found 633.1979.
2,20-((1s,3r,5s,7r)-4,6,10-Trioxo-7-(2-oxo-2-(phenylamino)
ethyl)-1-azaadamantane-3,5-diyl)bis(N-(4-dodecylphenyl)
acetamide) (1m)
To a solution of 4m (51 mg, 59 mmol) in i-PrOH was
added, HMTA (17 mg, 120 mmol) and the reaction mixture
was allowed to reflux over 2 nights. After cooling, the
insoluble material was isolated by filtration and washed
with 0.1 N HCl, i-PrOH and EtOAc before being dried in
vacuo to yield 1m (30 mg, 56%) as a white, flaky solid. 1H
NMR (d6-DMSO): d 0.85 (t, J ¼ 6.7 Hz, 6H), 1.23 (br s,
36H), 1.52 (m, 4H), 2.77 (m, 6H), 3.91 (m, 6H), 7.00
(t, J ¼ 7.3 Hz, 1H), 7.05 (d, J ¼ 8.2 Hz, 4H), 7.25
(t, J ¼ 7.8 Hz, 2H), 7.41 (d, J ¼ 8.1 Hz, 4H), 7.53
(d, J ¼ 8.0 Hz, 2H), 9.82 (s, 2H), 9.93 (s, 1H). 13C NMR
(d6-DMSO): d 13.76, 21.92, 28.41, 28.52, 28.69, 28.82,
28.85, 30.83, 31.12, 33.57, 34.38, 70.11, 70.23, 118.85,
118.92, 122.72, 128.10, 128.40, 136.67, 136.84, 139.18,
167.18, 167.41, 198.12, 198.16. HR-MS (ESI): calculated
for C57H79N4O6 [M þ H]þ 915.5994, found 915.5981.
N-(4-Methylesterphenyl)-2-(4,6,10-trioxo-5,7-di-4-methyl-
esterphenylcarbamoylmethyl-1-aza-tricyclo[3.3.1.13,7]
dec-3-yl)-acetamide (1h)
To a solution of 4h (42 mg, 60 mmol) in i-PrOH was added,
HMTA (25 mg, 180 mmol) and the reaction mixture was
heated to reflux over 3 nights. Solids from the reaction
mixture were removed by filtration, then washed and dried
to yield compound 1h (10 mg, 21%) as a slightly tan
powder. 1H NMR (d6-DMSO): d 2.82 (s, 6H), 3.81 (s, 9H),
3.93 (s, 6H), 7.67 (d, J ¼ 7.7 Hz, 6H), 7.88 (d, J ¼ 7.4 Hz,
6H), 10.40 (s, 3H). 13C NMR (d6-DMSO): d 33.81, 51.73,
70.16, 70.37, 118.17, 123.55, 130.15, 143.57, 165.74,
168.05, 198.27. HR-MS (ESI): calculated for
C39H37N4O12 [M þ H]þ 753.2402, found 753.2416.
2,20,200-((3s,5s,7s)-4,6,10-Trioxo-1-azaadamantane-3,5,7-
triyl)tris(N-(naphthalen-2-yl)acetamide) (1i)
2,20-((1r,3r,5s,7s)-7-(2-(Naphthalen-2-ylamino)-2-
oxoethyl)-4,6,10-trioxo-1-azaadamantane-3,5-diyl)bis(N-
phenylacetamide) (1n)
To a solution of 4i (49 mg, 0.072 mmol) in i-PrOH was
added, HMTA (30 mg, 0.22 mmol) and the reaction
mixture was heated to reflux for 120 h. After cooling, the
insoluble material was isolated, triturated with EtOAc,
isolated by filtration and washed to yield 1i (35 mg, 66%)
as a slightly tan solid. 1H NMR (d6-DMSO): d 2.88 (s, 6H),
4.00 (s, 6H), 7.37 (m, 3H), 7.44 (t, J ¼ 7.5 Hz, 3H), 7.52
(d, J ¼ 8.6 Hz, 3H), 7.80 (m, 9H), 8.29 (s, 3H), 10.24
(s, 3H). 13C NMR (d6-DMSO): d 33.84, 70.28, 70.46,
114.74, 119.80, 124.35, 126.31, 127.19, 127.38, 128.22,
129.54, 133.44, 136.51, 167.61, 198.31. HR-MS (ESI):
calculated for C45H36N4O6Na [M þ Na]þ 751.2517,
found 751.2517.
A solution of 4n (90 mg, 0.16 mmol), HMTA (66 mg,
0.48 mmol) and i-PrOH (5 ml) was heated to reflux for
2 days. After cooling to room temperature, the mixture was
filtered to afford an off-white solid. The solid was washed
with 5% HCl and water to afford 1n (41 mg, 43%) as an
off-white solid. 1H NMR (d6-DMSO): d 2.79 (s, 4H), 2.85
(s, 2H), 3.95 (s, 6H), 6.99 (t, J ¼ 7.5 Hz, 2H), 7.26 (t,
J ¼ 7.8 Hz, 4H), 7.45 (m, 8H), 7.81 (m, 3H), 8.27 (s, 1H),
10.01 (s, 2H), 10.23 (s, 1H). 13C NMR (d6-DMSO): d
33.21, 69.71, 69.88, 114.19, 118.35, 119.28, 122.33,
123.85, 125.81, 126.69, 126.88, 127.72, 128.08, 129.03,
132.95, 136.36, 138.80, 167.03, 167.28, 197.79. HR-MS
(ESI): calculated for C37H32N4O6 Na [M þ Na]þ
651.2214, found 651.2208.
2,20,200-((3s,5s,7s)-4,6,10-Trioxo-1-azaadamantane-3,5,7-
triyl)tris(N-(7-dodecyl-naphthalen-2-yl)acetamide) (1j)
To a solution of 4j (25 mg, 0.021 mmol) in i-PrOH was
added, HMTA (8.8 mg, 0.063 mmol) and the reaction
mixture was allowed to reflux for 120 h. After cooling, the
insoluble material was isolated, triturated with EtOAc,
again isolated by filtration and washed to yield 1j (17 mg,
2,20-(4,6-Dihydroxy-2-oxo-2,3-dihydrobenzofuran-5,7-
diyl)bis(N-phenylacetamide) (5)
To a solution of BTF (100 mg, 0.40 mmol) in DMF (2 ml)
was added dropwise, aniline solution (3.2 ml of a 0.5 M
solution, 1.6 mmol). The resulting solution was stirred
over 2 nights in a 708C oil bath, after which the reaction
was diluted with EtOAc (200 ml), washed with 0.3 N HCl,
DI H2O, then brine and dried over Na2SO4. The solvent
was removed in vacuo and the residue was purified by
column chromatography (1/10 acetone/DCM) to yield 5
(79 mg, 45%) as an off-white solid. 1H NMR (d6-DMSO):
d 3.67 (s, 2H), 3.68 (s, 2H), 3.74 (s, 2H), 7.03 (q,
J ¼ 7.6 Hz, 2 H), 7.34–7.23 (m, 4H), 7.59 (d, J ¼ 7.9 Hz,
4 H), 9.55 (s, 1 H), 9.70 (s, 1 H), 10.05 (s, 1 H), 10.24 (s,
1
65%) as a white powder. H NMR (d5-pyridine): d 0.87
(t, J ¼ 6.9 Hz, 9H), 1.29 (m, 60H), 1.67 (m, 6H), 2.73
(t, J ¼ 7.6 Hz, 6H), 4.37 (s, 6H), 7.38 (d, J ¼ 8.2 Hz, 3H),
7.68 (s, 3H), 7.8 (d, J ¼ 8.5 Hz, 3H), 7.87 (m, 6H), 8.61 (s,
3H), 11.73 (s, 3H). 13C NMR (d5-pyridine): d 14.98, 23.63,
26.75, 28.34, 30.30, 30.33, 30.53, 30.60, 30.65, 32.40,
32.81, 36.90, 72.11, 75.87, 117.39, 121.57, 127.24,
128.55, 129.02, 131.75, 133.74, 140.11, 169.59, 200.21.
HR-MS (ESI): calculated for C81H108N4O6Na [M þ Na]þ
1255.8167, found 1255.8136.

Supramolecular Chemistry
801
1H). 13C NMR (d6-DMSO): d 31.63, 31.77, 31.92, 98.43,
100.53, 106.69, 119.02, 119.25, 123.00, 123.37, 128.65,
128.70, 138.92, 139.27, 150.45, 152.18, 155.02, 169.69,
170.31, 174.63. HR-MS (ESI): calculated for C24H22N2O6
[M þ H]þ 433.1394, found 433.1389.
(5) Hoffmann, R.; Imamura, A.; Hehre, W.J. J. Am. Chem. Soc.
1968, 90, 1499–1509.
(6) Alabugin, I.V.; Manoharan, M. J. Org. Chem. 2004, 69,
9011–9024.
(7) Alabugin, I.V.; Zeidan, T.A. J. Am. Chem. Soc. 2002, 124,
3175–3185.
(8) Lambert, J.B.; Zhao, Y.; Emblidge, R.W.; Salvador, L.A.;
Liu, X.; So, J.-H.; Chelius, E.C. Acc. Chem. Res. 1999, 32,
183–190.
2-(4-Hydroxy-2,7-dioxo-2,3,7,8-tetrahydrobenzo[1,2-b:3,
4-b0]difuran-5-yl)-N-phenylacetamide (6)
(9) Kardel, D.; Knoche, W.; Risch, N. J. Chem. Soc. Perkin
Trans. 2 1993, 1455–1459.
To a solution of BTF (100 mg, 0.40 mmol) in DMF
(600 ml) was added dropwise, aniline solution (560 mg in
12 ml DMF, 6.0 mmol). The resulting solution was
allowed to stir for 8 h in a 408C oil bath. The reaction
mixture was next diluted with EtOAc (200 ml), washed
with 0.3 N HCl, DI H2O, then brine and dried over
Na2SO4. The solvent was removed in vacuo and the
residue was purified by column chromatography (1/20
acetone/DCM) to yield 6 (76 mg, 56%) as an off-white
(10) Risch, N.; Langhals, M.; Hohberg, T. Tetrahedron Lett.
1991, 32, 4465–4468.
¨
(11) Risch, N.; Langhals, M.; Mikosch, W.; Bogge, H.;
Mu¨ller, A. J. Am. Chem. Soc. 1991, 113, 9411–9412.
(12) Lampkins, A.J.; Abdul-Rahim, O.; Li, H.; Castellano, R.K.
Org. Lett. 2005, 7, 4471–4474.
(13) Li, H.; Homan, E.A.; Lampkins, A.J.; Ghiviriga, I.;
Castellano, R.K. Org. Lett. 2005, 7, 443–446.
(14) Wu¨rthner, F.; Yao, S.; Beginn, U. Angew. Chem. Int. Ed.
2003, 42, 3247–3250.
(15) Harikumar, K.R.; Lim, T.B.; McNab, I.R.; Polanyi, J.C.;
Zotti, L.; Ayissi, S.; Hofer, W.A. Nat. Nanotechnol. 2008,
3, 222–228.
(16) Sumpter, B.G.; Meunier, V.; Valeev, E.F.; Lampkins, A.J.;
Li, H.; Castellano, R.K. J. Phys. Chem. C 2007, 111,
18912–18916.
1
solid. H NMR (d6-DMSO): d 3.66 (s, 2H), 3.80 (s, 2H),
3.95 (s, 2H), 7.03 (t, J ¼ 7.4 Hz, 1H), 7.29 (t, J ¼ 7.9 Hz,
2H), 7.59 (d, J ¼ 8.1 Hz, 7H), 10.07 (s, 1H), 10.13 (s, 1H).
13C NMR (d6-DMSO): d 30.6, 31.1, 31.4, 97.1, 102.6,
104.8, 118.9, 123.0, 128.7, 139.2, 147.8, 151.3, 153.7,
168.3, 173.9, 174.1. HR-MS (ESI): calculated for
C18H15NO6 [M þ H]þ 340.0816, found 340.0813.
´
´
(17) Sumpter, B.G.; Meunier, V.; Vazquez-Mayagoitia, A.;
Castellano, R.K. Int. J. Quantum. Chem. 2007, 107,
2233–2242.
(18) Li, Y.; Lampkins, A.J.; Baker, M.B.; Sumpter, B.G.;
Huang, J.; Abboud, K.A.; Castellano, R.K. Org. Lett. 2009,
11, 4314–4317.
(19) Ringsdorf, H.; Wu¨stefeld, R.; Zerta, E.; Ebert, M.;
Wendorff, J.H. Angew. Chem. Int. Ed. Engl. 1989, 28,
914–918.
Supplementary materials
Details of the synthesis of 7-dodecyl-2-aminonaphthalene,
solubility and gelation profiles for selected AAT
1
derivatives, and copies of the H NMR spectra for all
new compounds are available online.
(20) Reczek, J.J.; Iverson, B.L. Macromolecules 2006, 39,
5601–5603.
(21) Reczek, J.J.; Villazor, K.R.; Lynch, V.; Swager, T.M.;
Iverson, B.L. J. Am. Chem. Soc. 2006, 128, 7995–8002.
(22) Meyer, E.A.; Castellano, R.K.; Diederich, F. Angew. Chem.
Int. Ed. 2003, 42, 1210–1250.
(23) Hirst, A.R.; Smith, D.K. Chem. Eur. J. 2005, 11,
5496–5508.
Acknowledgements
This work was financially supported by the National Science
Foundation CAREER programme (CHE-0548003). MBB and
YL were supported by a University of Florida (UF) Alumni
Graduate Fellowship and CLAS Dissertation Fellowship,
respectively. CJM would like to thank the HHMI-UF Science
for Life Program for an Undergraduate Research Award and the
Barry M. Goldwater Scholarship and Excellence in Education
Program for funding. We are grateful to Dr Kerry Siebein and the
Major Analytical Instrumentation Center (MAIC), Department of
Materials Science and Engineering, University of Florida, for
SEM and TEM imaging. The authors would also like to thank the
personnel in Mass Spectrometry Services, Department of
Chemistry, University of Florida, for diligent characterisation
of the molecules presented in this paper.
(24) Yagai, S.; Higashi, M.; Karatsu, T.; Kitamura, A. Chem.
Mat. 2005, 17, 4392–4398.
(25) Cozzi, F.; Siegel, J.S. Pure Appl. Chem. 1995, 67, 683–689.
(26) Lehmann, M. Chem. Eur. J. 2009, 15, 3638–3651.
(27) Lindsey, J.S. Acc. Chem. Res. 2010, 43, 300–311.
(28) Chen, C.; Dagnino, R., Jr.; McCarthy, J.R. J. Org. Chem.
1995, 60, 8428–8430.
(29) Dogutan, D.K.; Zaidi, S.H.H.; Thamyongkit, P.; Lindsey,
J.S. J. Org. Chem. 2007, 72, 7701–7714.
(30) Jain, R.K.; Tsou, L.K.; Hamilton, A.D. Tetrahedron Lett.
2009, 50, 2787–2789.
(31) Lehmann, M.; Jahr, M. Org. Lett. 2006, 8, 721–723.
(32) Naito, H.; Hata, T.; Urabe, H. Org. Lett. 2010, 12,
1228–1230.
References
(33) Mooibroek, T.J.; Gamez, P. Inorg. Chim. Acta 2007, 360,
381–404.
(34) Estroff, L.A.; Hamilton, A.D. Chem. Rev. 2004, 104,
1201–1217.
(35) Gronwald, O.; Snip, E.; Shinkai, S. Curr. Opin. Colloid
Interface Sci. 2002, 7, 148–156.
(36) Terech, P.; Weiss, R.G. Chem. Rev. 1997, 97, 3133–3159.
(1) Lampkins, A.J.; Li, Y.; Al Abbas, A.; Abboud, K.A.;
Ghiviriga, I.; Castellano, R.K. Chem. Eur. J. 2008, 14,
1452–1463.
(2) Risch, N. J. Chem. Soc. Chem. Commun. 1983, 532–533.
(3) Yuan, L.; Sumpter, B.G.; Abboud, K.A.; Castellano, R.K.
New J. Chem. 2008, 32, 1924–1934.
(4) Hoffmann, R. Acc. Chem. Res. 1971, 4, 1–9.

802
M.B. Baker et al.
(37) Takahashi, A.; Sakai, M.; Kato, T. Polym. J. 1980, 12,
335–341.
(41) Yamanaka, M.; Fujii, H. J. Org. Chem. 2009, 74,
5390–5394.
(42) Land, V.D.; Harris, T.M.; Teeters, D.C. J. Non-Cryst. Solids
2001, 283, 11–17.
(43) Wang, R.Y.; Liu, X.Y.; Xiong, J.Y.; Li, J.L. J. Phys. Chem.
B 2006, 110, 7275–7280.
(44) Schenning, A.; Meijer, E.W. Chem. Commun. 2005,
3245–3258.
(38) Moffat, J.R.; Smith, D.K. Chem. Commun. 2009, 316–318.
(39) Li, X.Q.; Stepanenko, V.; Chen, Z.J.; Prins, P.; Siebbeles,
L.D.A.; Wu¨rthner, F. Chem. Commun. 2006, 3871–3873.
(40) Suzuki, M.; Hanabusa, K. Chem. Soc. Rev. 2009, 38,
967–975.