Fine-tuning the dimerization of tetraureacalix [4] arenes

Article abstract of DOI:10.1002/chem.201000024

Calix[4]arenes substituted by four urea residues at their wide rim form hydrogen-bonded homo- and heterodimeric capsules in apolar solvents. If urea groups are covalently connected to loops or substituted by bulky residues, the dimerization may be restricted to those pairs in which the loops do not overlap and for which the residues are small enough to pass the loops. In the present study, we describe the dimerization properties of tetraureas with one, two (adjacent or opposite), three, or four loops and those bearing (additionally) up to four residues of different size: a = tolyl, b = 3,5-di-tertbutylphenyl, c=4-propyloxy-3,5-di(tert-butylphenyl)phenyl, and d = 4-[tris-(4-tert- butylphenyl)methyl]phenyl. For compounds with four loops of different size (-O-(CH₂)_n-O-, with n= 10,14, and 20 connecting the /-positions of the urea phenyl residues) a clear stepwise sorting scheme could be established, in which the bulkiest residue d is excluded by all tetraloop compounds and the smallest residue a can pass only the smallest loops (n = 10). The medium-sized residues b or c are tolerated by = 14 and 20 or only by H = 20. Selectivities can be built up also on geometrical factors. A trisloop compound, for instance, combines only with a tetraurea bearing a single bulky residue and tetraureas with two bulky substituents in adjacent or opposite position are distinguished by the bisloop derivatives with adjacent or opposite loops. The impossibility to form a homodimer of a monoloop compound containing two bulky residues leads to its selective heterodimerization with a derivative bearing three bulky groups. Subtle effects for borderline cases, in which the dimerization or reorganization takes a longer time, are also discussed.

Full text of DOI:10.1002/chem.201000024

FULL PAPER
DOI: 10.1002/chem.201000024
Fine-Tuning the Dimerization of Tetraureacalix[4]arenes
Yuliya Rudzevich,*[a] Valentyn Rudzevich,[a, b] and Volker Bçhmer*[a]
Abstract: Calix[4]arenes substituted by
[tris-(4-tert-butylphenyl)methyl]phenyl.
also on geometrical factors. A trisloop
four urea residues at their wide rim
form hydrogen-bonded homo- and het-
erodimeric capsules in apolar solvents.
If urea groups are covalently connected
to loops or substituted by bulky resi-
dues, the dimerization may be restrict-
ed to those pairs in which the loops do
not overlap and for which the residues
are small enough to pass the loops. In
the present study, we describe the di-
merization properties of tetraureas
with one, two (adjacent or opposite),
three, or four loops and those bearing
(additionally) up to four residues of
different size: a=tolyl, b=3,5-di-tert-
For compounds with four loops of dif-
compound, for instance, combines only
with a tetraurea bearing a single bulky
residue and tetraureas with two bulky
substituents in adjacent or opposite po-
sition are distinguished by the bisloop
derivatives with adjacent or opposite
À À
À
ferent size ( O (CH2)n O-chains with
AHCTUNGTRENNUNG
n=10, 14, and 20 connecting the m-po-
sitions of the urea phenyl residues) a
clear “stepwise” sorting scheme could
be established, in which the bulkiest
residue d is excluded by all tetraloop
compounds and the smallest residue a
can pass only the smallest loops (n=
10). The medium-sized residues b or c
are tolerated by n=14 and 20 or only
by n=20. Selectivities can be built up
loops. The impossibility to form
a
homodimer of a monoloop compound
containing two bulky residues leads to
its selective heterodimerization with a
derivative bearing three bulky groups.
Subtle effects for “borderline” cases, in
which the dimerization or reorganiza-
tion takes a longer time, are also dis-
cussed.
Keywords: calixarenes · dimeriza-
tion · hydrogen bonds · self-assem-
bly · supramolecular chemistry
butylphenyl,
c=4-propyloxy-3,5-di-
(tert-butylphenyl)phenyl, and d=4-
Introduction
tages of self-assembly cannot be overestimated. Usually it
does not require complicated syntheses, whereas it often af-
fords “quantitative” yields, since wrong connections between
the building blocks are automatically repaired.
Hydrogen bonding is one of the tools for self-organiza-
tion, which is frequently chosen also by nature. In contrast
to other reversible interactions, there is still a “certain direc-
tionality”, which can be used to build artificial assemblies or
to construct complex supramolecular structures.
The fascinating area of “self-assembly” presently attracts
the attention of many scientists. Starting with a small
number of selected “building blocks” it offers almost unlim-
ited possibilities for the construction of various intriguing ar-
chitectures[1] and allows the realization of rather ambitious
ideas. From a synthetic point of view, the additional advan-
Tetraureacalix[4]arenes 1, which form hydrogen-bonded,
dimeric capsules[2] in apolar solvents (Scheme 1), represent a
system that is particularly interesting. Various multimacrocy-
clic compounds,[3] numerous catenanes[3b,4] and rotaxanes,[5]
hydrogen-bonded polymers,[6] informational (or “smart”)
polymers,[7] and self-assembled dendritic architectures[8]
were developed based on this dimerization.
To realize some of the mentioned structures an exclusive
heterodimerization of two different tetraureas has been re-
quired for which until now only a few examples are known.
The stoichiometric mixture of a tetraaryl urea 1 and a tetra-
tosyl urea 2, for instance, contains only the heterodimer 1·2,
whereas a mixture of two (similar) tetraaryl (or tetraalkyl)
[a] Dr. Y. Rudzevich, Dr. V. Rudzevich, Dr. V. Bçhmer
Abteilung Lehramt Chemie, Fachbereich Chemie
Pharmazie und Geowissenschaften
Johannes Gutenberg-Universitꢀt
Duesbergweg 10–14
55099 Mainz (Germany)
Fax : (+49)6131-3925419
E-mail: rudzevic@mail.uni-mainz.de
vboehmer@mail.uni-mainz.de
[b] Dr. V. Rudzevich
Permanent address: Institute of Organic Chemistry
NAS of Ukraine, Murmanska str. 5, 02094 Kyiv-94 (Ukraine)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000024.
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4541

ureas usually contains the two homodimers and the respec-
tive heterodimer.[9] The serendipitous observation of this
heterodimerization was the first example of an exclusive
“social self-sorting behavior” reported for the dimerization
of tetraureacalix[4]arenes.[10,11] It occurs due to a subtle dif-
ference in the hydrogen-bonding pattern of arylurea and to-
sylurea groups, which requires a sterically less-favorable
conformation for half of the tosylurea residues in the homo-
dimer 2·2.[12]
During our attempts to obtain inherently chiral dimers
from achiral tetraureacalix[4]arenes[13] we have studied com-
pounds of the AABB-type 3a,[4] in which two adjacent urea
residues are covalently connected by an aliphatic chain to
form a “loop”. The observation of only one of two potential
regioisomeric homodimers strongly suggested that dimers
with overlapping loops cannot be formed, whereas those be-
tween open-chained and loop-containing tetraureas can and
should be formed exclusively. Indeed, solutions containing
the calixarenes 4–7 show only broad NMR spectra, since for
the dimerization no arrangement can be found in which
Scheme 1. Top: Dimeric capsule of a tetraaryl tetraureacalix[4]arene 1:
a) side view; b) top view, hydrogen bonds are indicated by dashed lines;
c) graphical representation of the dimer. Bottom: Structural formulae of
tetraaryl and tetratosyl tetraureacalix[4]arenes 1 and 2.
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Fine-Tuning the Dimerization of Tetraureacalix[4]arenes
FULL PAPER
loops are not overlapping. Thus, their mixtures with tetra-
ACHTUNGTRENNUNG
By using these observations, a selective dimerization
based on incompatible sizes of loops and urea residues can
be developed. Thus, when the six tetraureas 1a–c and 7a–c
are mixed in stoichiometric amounts,[18] only three hetero-
dimers 1a·7a, 1b·7b, and 1c·7c (from nine possible hetero-
dimeric combinations) are observed in solution (Figure 1d).
A
ACHTUNGTRENNUNG
Recently, we could extend this selectivity, showing that
bulky urea residues can be found that make the formation
of certain tetraurea dimers impossible, since they cannot
pass a respective loop.[14] Tentatively two basic rules for the
dimerization of tetraureacalix[4]arenes were formulated:
1) Dimers with overlapping loops cannot be formed.
2) Dimers cannot be formed if a bulky residue has to pass a
loop.
The first rule has been confirmed for various examples
À
À
with O ACHTUNGTRENNUNG(CH2)n O chains up to n=20 connecting the m-po-
sitions[15] of phenylureas. Never was the formation of capsu-
les with overlapping loops observed.
Based on loops with n=10 and bulky residues 4-propyl-
ACHTUNGTRENNUNGoxy-3,5-di-(tert-butylphenyl)phenyl that cannot pass these
loops, a sorting scheme could be realized for 11 tetraureas,
for which instead of 0.5ꢂ11ꢂ(11+1)=66 dimers only 6
dimers are formed.[16]
In this paper we describe the fine-tuning of the second
rule, establishing a correlation between the size of “bulky”
substituents and the length of the loops by which the pene-
tration can be safely excluded.
Results and Discussion
Control by size: To check the compatibility between loops
and bulky residues of different sizes the tetraureas 1a–d
were mixed with tetraloop compounds 7a–c under condi-
tions suitable for the dimerization. Table 1 summarizes re-
Figure 1. Sections of the 1H NMR spectra (400 MHz, CDCl3, 258C) of
a) the heterodimer 1a·7a, b) the heterodimer 1b·7b, c) the heterodimer
1c·7c, d) the mixture of heterodimers 1a·7a, 1b·7b, and 1c·7c, and e) the
homodimer 1d·7d.
Table 1. Dimerization of tetraureas 1a–d with 7a–c.
Compound
1a
1b
1c
1d
This can be easily explained by the rules mentioned above.
Due to the first rule, the tetraloop derivatives 7a–c cannot
form dimers with each other, although the tendency to di-
merize is peculiar to all tetraureas. From the three proposed
partners 1a–c, 7a can form a capsule only with 1a (Fig-
ure 1a), since the urea residues of 1b,c are too large to pass
through its loops (second rule). Therefore, 1a and 7a are
completely consumed, forming a heterodimer. According to
the same principle 1b is paired with 7b. Finally, the only
partner remaining for 1c is the tetraurea 7c (Figure 1c). A
mixture containing additionally the bulkiest tetraurea 1d
would contain additionally also its homodimer 7d·7d (four
dimers from 16 sterically possible combinations).[19]
7a (n=10)
7b (n=14)
7c (n=20)
+
+
+
À
+
+
À
À
+
À
À
À
sults obtained for all combinations within three days after
mixing (a complete scheme, containing also all homodimers
is shown in Figure S1, Supporting Information). The smallest
tetratolyl urea 1a easily forms dimers with all tetraloop de-
rivatives 7a–c, whereas the 3,5-di-tert-butylphenyl residues
of 1b are already too large to pass through the loops of 7a
(n=10). The replacement of the tert-butyl groups in 1b by
the 4-tert-butylphenyl residues (1c) makes the formation of
the dimers 1c·7a and 1c·7b impossible; however, the capsu-
le 1c·7c was observed immediately after mixing. Finally, no
heterodimers were found in the mixtures of the tetraurea 1d
that bears the most voluminous substituents with any of the
proposed tetraloop compounds 7.[17]
Control by geometry: Selective dimerization can be also
controlled by the number (or the position) of the loops of
one calixarene and the number and position of the bulky
residues of the partner (Scheme 2). In accordance to the
rules described above the tetraloop derivative 7a[20] can
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4543

V. Bçhmer, Y. Rudzevich, and V. Rudzevich
AHCTUNGTRENNUNG
Subtle effects and borderline cases: The simple picture de-
scribed above is not entirely correct, when tetraurea mole-
cules with loops of larger size (n>10) are studied. Although
1b (with four medium-sized residues) does not form hetero-
dimers with 7a (containing four small loops),[22] the solution
of the monoloop compound 3b in CDCl3 contains only the
homodimer 3b·3b after three days, as shown by the clear
NMR spectrum in Figure 2. In the characteristic NH region
Figure 2. Sections of the 1H NMR spectra (400 MHz, CDCl3, 258C) of
the monoloop derivative 3b a) immediately after mixing, b) 1 day after
mixing, and c) 3 days after mixing.
Scheme 2. Schematic representation of the selective recognition con-
trolled by geometry.
of the spectrum,[23] eight signals corresponding to the NHa
protons of the dimer can be clearly observed. This shows
that the mutual penetration of a single loop with n=10 by a
3,5-di-tert-butylphenyl residue is obviously possible.
Much slower formation of heterodimers is observed when
the bisloop compound 5 (n=10) is added to the homodimer
1b·1b. Like the tetraloop compound 7a, the bisloop ana-
logue 5 cannot form homodimers due to overlapping loops.
However, its tendency to dimerize is obviously strong
enough to form heterodimers with 1b, and after three weeks
the signals of the homodimer 1b·1b are practically com-
pletely replaced by those of the heterodimer 5·1b.
This seeming “contradiction”, the fact that 1b can pene-
trate the two loops of 5 and not the four equally sized loops
of 7a can be understood by a higher flexibility of 5 in com-
parison to 7a, and by a “pinched” cone conformation of 1b,
which allows its combination with the bisloop 5, but is detri-
mental to the dimerization with 7a, since in the said confor-
form heterodimers only with tetraurea 1a containing four
small residues. Consequently, a partner for the trisloop de-
rivative 6[3a] can possess only one bulky substituent, whereas
the monoloop derivative 3c[21] can dimerize with a tetraurea
bearing three bulky residues. For the bisloop derivatives 4[3a]
and 5,[3b] two bulky residues are potentially possible, provid-
ed they have the appropriate position.
Equimolar mixtures of the bisloop compound 5 with 9 or
of bisloop compound 4 with 10 do not contain heterodimers.
Their spectra correspond to the homodimers 9·9 and 10·10,
respectively, accompanied by broad signals for unpaired 4 or
5. However, if these two solutions 5/9 and 4/10 are com-
bined, the NMR spectrum is in total agreement with a mix-
ture of the two heterodimers 4·9 and 5·10 (compare Fig-
ure S2, Supporting Information).
The tetraureacalix[4]arenes 1c or 1d bearing four (more
or less) bulky substituents should not be able to form het-
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Chem. Eur. J. 2010, 16, 4541 – 4549

Fine-Tuning the Dimerization of Tetraureacalix[4]arenes
FULL PAPER
mation two of the di-tert-butylphenyl urea residues are bent
outwards. The pinched cone conformation necessary for the
passage of two opposite urea residues through two opposite
loops hinders the passage of the two urea groups bent out-
wards through the remaining loops! The observation that
heterodimers are not formed in the mixtures of 1b/4 and
1b/6 confirms this suggestion.
This explanation is additionally substantiated by the fol-
lowing observation. A 1:1 mixture of tetraureas 12 and 3b
contains only one heterodimer (exclusively!) immediately
after mixing, since the homodimerization of 3b is kinetically
slower than the formation of 3b·12, with the tolyl residue
penetrating the loop. However, in the same measure, as
3b·3b is slowly formed, also the homodimers 12·12 (two re-
gioisomers), the two other regioisomeric heterodimers 3b·12
(with a bulky residue passing the loop) appear. This leads fi-
nally to a much more complicated NMR spectrum (see Fig-
ure S3, Supporting Information).
Syntheses: The synthesis of a bulky acylating agent necessa-
ry to prepare tetraureas 1c, 3c, and 8–11 is shown in
Scheme 3. Alkylation of 2,6-dibromo-4-nitrophenol 13 with
propyl iodide in the presence of K2CO3 afforded compound
14 in 95% yield. It was converted in the next step to 15
(76%) by Suzuki coupling with 4-tert-butylphenylboronic
acid. The catalytic hydrogenation to 16 (100%), followed by
its reaction with 4-nitrophenyl chloroformate finally gave
the active urethane 17 in 85% yield. Isocyanate 18 was pre-
pared in situ from the aniline 16 and triphosgene in toluene
and was used without additional purification.
Tetraureas 8 and 10 were made from the known tritolyl
urea monoamine[24] and 1,3-ditolylurea-2,4-diamine,[25] re-
spectively, by acylation with isocyanate 18.
The synthesis of the 1,2-di-bulky tetraurea 9 and the
monoACTHNUTRGENUlGN oop derivative 3c is illustrated in Scheme 4. The
amine 19, tert-butoxycarbonyl (Boc)-protected in the 1,2-po-
sitions,[26] was reacted with tolyl isocyanate or with the
active urethane 22 to give the di-ureas 20a and 20b both in
68% yield. Deprotection and subsequent acylation with iso-
Scheme 3. Synthesis of a bulky acylating agent. i) PrI, K2CO3, CH3CN; ii) 4-tert-butylphenylboronic acid; Na2CO3, Pd
Ni, toluene/EtOH; iv) p-nitrophenyl chloroformate, THF/CHCl3; v) triphosgene, toluene.
ACHTUNGTRNE(NUNG PPh3)4, dioxane/water; iii) Raney-
Scheme 4. Synthesis of the tetraureas 3b and 9. i) Tol-NCO, CH2Cl2 for 20a; active urethane 22, Et3N, CHCl3, reflux for 20b; ii) trifluoroacetic acid
(TFA), CH2Cl2; 18, toluene; iii) for 21 Grubbs catalyst, CH2Cl2/C6H6; reduction (PtO2).
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V. Bçhmer, Y. Rudzevich, and V. Rudzevich
periments confirmed the assignments of the signals. Mass spectra were
recorded on a Waters/Micromass QTof Ultima 3 mass spectrometer. All
solvents were HPLC grade and used without further purification.
Column chromatography was performed on silica gel 60 (0.035–
0.070 mm, Acros).
cyanate 18 led to the tetraureas 9 (90%) and 21 (89%) with
two bulky urea residues. Tetraurea 21 was finally converted
to the monoloop derivative 3c (54%) by olefin metathesis
and subsequent hydrogenation.
As previously verified,[27] data for elemental analyses of organic calixar-
enes are often misleading, due to inclusion of solvent molecules, and
cannot be considered appropriate criteria of purity. However, the identi-
ties of the reported compounds were unambiguously established by their
spectroscopic data.
Compounds 1a,[9] 1d,[28] 3a,[4] 4,[3a] 5,[3b,c] 6,[3a] 7a,[20] 7b,[3c] and 7c[29] were
prepared according to previously reported procedures.
The synthesis of the tetraureas 1c and 11 started with the
tetraamino calix[4]arene 23 (Scheme 5). Compound 1c
(89%) was obtained directly through the reaction of 23 with
isocyanate 18. The acylation with the active urethane 17,
which was used as a mild acylating agent since it allows tri-
substituted products to be formed with higher yields without
column purification, afforded the respective tri-urea mono-
amine derivative 24 (73%). In the last step, it was easily
converted to 11 (76%) with tolyl isocyanate.
2,6-Dibromo-1-propoxy-4-nitrobenzene (14): A mixture of 2,6-dibromo-
4-nitrophenol 13 (7.00 g, 23.6 mmol), K2CO3 (16.3 g, 118 mmol), and
propyl bromide (14.5 g, 10.7 mL, 118 mmol) was refluxed for 4 days in
CH3CN (250 mL). When the alkylation was complete, the color of the
mixture changed from bright orange to pale yellow (the conversion was
controlled by TLC, CHCl3/hexane 1:3). Water (20 mL) was added to dis-
solve K2CO3 and CH3CN was evaporated under reduced pressure. Then
water (150 mL) was added to the residue, the precipitate was filtered,
washed with water, and dried in air. Compound 14 (7.59 g, 95%) was ob-
tained as a yellow solid. M.p. 66–688C; 1H NMR (400 MHz, CDCl3,
258C): d=1.11 (t, 3J
ACHTNUTRGNE(NUG H,H)=7.3 Hz, 3H; CH3), 1.88–1.97 (m, 2H; CH2),
4.06 (t, 3J
ACTHNUGTRNE(NUG H,H)=6.6 Hz, 2H; OCH2), 8.40 ppm (s, 2H; ArH); MS (FD):
m/z (%): calcd for C9H9Br2NO3: 338.98; found: 339.0 (100) [M]+.
2,6-Bis(4-tert-butylphenyl)-1-propoxy-4-nitrobenzene (15): Nitrogen was
bubbled for 1 h through a solution of 14 (3.17 g, 9.35 mmol), 4-tert-butyl-
phenylboronic acid (4.99 g, 28.1 mmol), and Na2CO3 (8.92 g, 84.2 mmol)
in 1,4-dioxane/water (300:80 mL); then PdACHTNUTRGNE(UNG PPh3)4 (1.62 g, 1.40 mmol)
was added and the reaction mixture was stirred at 758C for 24 h, cooled
down and evaporated. The residue was dissolved in dichloromethane
(200 mL), washed with water (3ꢂ100 mL), and dried (MgSO4). The sol-
vent was evaporated and the crude product was purified by column chro-
matography (CHCl3/hexane 1:3). Compound 15 (3.17 g, 76%) was ob-
Scheme 5. Synthesis of the tetraureas 1c and 11. i) 18, toluene; ii) 17,
Et3N, CHCl3, reflux; iii) Tol-NCO, CH2Cl2.
tained as a light-yellow powder. M.p. 130–1328C; 1H NMR (400 MHz,
3
CDCl3, 258C): d=0.51 (t, J
CH2), 1.37 (s, 18H; C
(H,H)=7.6 Hz, 3H; CH3), 1.17–1.24 (m, 2H;
3
Conclusion
ACHTUGTNRNENUG(CH3)3), 3.25 (t, JACTHUNGTRENNNUG
(d, 3J(H,H)=8.3 Hz, 4H; ArH), 7.54 (d, 3J
A
ACHTUNGTRENNUNG
8.21 ppm (s, 2H; ArH); MS (FD): m/z (%): calcd for C29H35NO3: 445.61;
found: 445.1 (100) [M]+.
A simple rule for the dimerization of tetraurea calix[4]ar-
enes emerges: a dimer cannot be formed if a bulky residue
attached to the urea function has to pass (through) a loop
connecting two adjacent urea functions. This rule has been
extended and further differentiated. Four tetraurea calix[4]-
arenes bearing residues with increasing size were synthe-
sized, which can distinguish three different tetraloop tetraur-
ea calix[4]arenes. For tetraureacalix[4]arenes bearing one to
three loops or bulky substituents examples were found for
which the dimerization is controlled by this number and by
their position. These results offer further possibilities to con-
trol the formation of dimers in mixtures of tetraureacalix[4]-
arenes. Their use for the construction of suitable building
blocks by the covalent connection of appropriate tetraurea-
calix[4]arenes via their narrow rim finally will lead to the
construction of well-defined assemblies under conditions
suitable for the dimerization of tetraureacalix[4]arenes.
2,6-Bis(4-tert-butylphenyl)-1-propoxy-4-aminobenzene (16): The terphen-
yl 15 (0.50 g, 1.12 mmol) was dissolved in toluene/ethanol (20:5 mL) and
hydrogenated for 8 h at room temperature in the presence of Raney-Ni.
The catalyst was filtered off and washed with toluene (2ꢂ10 mL). The
combined organic solutions were evaporated under reduced pressure.
Amine 16 (0.47 g, 100%) was obtained as a light-brown powder. M.p.
117–1198C; 1H NMR (400 MHz, CDCl3, 258C): d=0.47 (t, 3J
7.3 Hz, 3H; CH3), 1.09–1.17 (m, 2H; CH2), 1.35 (s, 18H; C(CH3)3), 3.08
(H,H)=6.4 Hz, 2H; OCH2), 3.59 (brs, 2H; NH2), 6.67 (s, 2H; ArH),
7.40 (d, 3J(H,H)=8.3 Hz, 4H; ArH), 7.52 ppm (d, 3J
(H,H)=8.3 Hz, 4H;
ACHTUNGTRENNUNG(H,H)=
AHCTUNGTRENNUNG
3
(t, JACHTGNUTRENNUNG
A
ACHTUNGTRENNUNG
ArH); MS (FD): m/z (%): calcd for C29H37NO: 415.62; found: 415.1
(100) [M]+.
4-Nitrophenyl-N-[3,5-bis(4-tert-butylphenyl)-4-propoxyphenyl]carbamate
(17): A solution of amine 16 (0.47 g, 1.13 mmol) and 4-nitrophenyl
chloroACHTUNGRTNENUfG ormate (0.30 g, 1.47 mmol) in CHCl3/THF 1:1 (50 mL) was re-
fluxed for 12 h. The solvents were evaporated and the product was pre-
cipitated from Et2O/hexane. Active urethane 17 (0.56 g, 85%) was ob-
tained as light-yellow flakes. M.p. 171–1738C; 1H NMR (400 MHz,
3
CDCl3, 258C): d=0.50 (t, J
CH2), 1.35 (s, 18H; C
G
3
ACHTUGTNRNENUG(CH3)3), 3.15 (t, JACTHUNGTRENNNUG
(brs, 1H; NH), 7.38–7.43 (m, 8H; ArH), 7.54 (d, 3J
ArH), 8.27 ppm (d, 3J
ACTHUNRTGNE(GNU H,H)=9.3 Hz, 2H; ArH); MS (ESI): m/z (%):
calcd for C36H40N2O5: 580.73; found: 603.3 (12) [M+Na]+, 1183.7 (17)
[2M+Na]+, 1765.0 (26) [3M+Na]+.
Experimental Section
General: Melting points are uncorrected. 1H and 13C NMR spectra were
2,6-Bis(4-tert-butylphenyl)-1-propoxy-4-isocyanatobenzene (18): Triphos-
gene (0.24 g, 0.79 mmol) was added to the solution of aniline 16 (0.33 g,
0.79 mmol) in toluene (20 mL) under nitrogen. The solution was stirred
for 0.5 h at room temperature, 1 h at 508C, and 1 h at 808C. The toluene
recorded on
a Bruker Avance DRX 400 spectrometer at 400 and
100.6 MHz, respectively. Chemical shifts are reported in d units (ppm)
with reference to the residual solvent peaks. Decoupling and DEPT ex-
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Fine-Tuning the Dimerization of Tetraureacalix[4]arenes
FULL PAPER
was removed under reduced pressure (bath temperature: ~708C), tolu-
ene (20 mL) was added and evaporated once again. The isocyanate 18
obtained in this way was used without further purification.
ix[4]arene 19[26] (0.41 g, 0.42 mmol), active urethane 22[4] (0.45 g,
1.27 mmol), and Et3N (0.2 mL) in CHCl3 (25 mL) was refluxed for
3 days. The reaction mixture was diluted with chloroform (50 mL),
washed with a 15% aqueous solution of K2CO3 (4ꢂ20 mL) and then
with water (3ꢂ20 mL), dried (MgSO4), and evaporated. The residue was
purified by column chromatography (ethyl acetate/hexane 1:4). Calix[4]-
arene 20b (0.40 g, 68%) was obtained as a white powder. M.p. 165–
1678C (dec); 1H NMR (400 MHz, [D6]DMSO, 258C): d=0.93 (m, 12H;
5,11,17,23-TetrakisACHTUNGTRENNUNG[3,5-bis(4-tert-butylphenyl)-4-propoxyphenylureido]-
25,26,27,28-tetrapentoxycalix[4]arene (1c): Tetraamino calix[4]arene
23[30] (0.10 g, 0.13 mmol) was added to a solution of freshly prepared iso-
cyanate 18 (0.79 mmol) in toluene (20 mL) under nitrogen and the mix-
ture was stirred overnight at room temperature. Then methanol (70 mL)
was added, the precipitate was filtered, and dried in air. Tetraurea 1c
CH3), 1.37 (m, 34H; CH2, C
(m, 4H; CH2), 1.88–1.91 (m, 8H; CH2), 2.04–2.10 (m, 4H; CH2), 3.01 (d,
2J(H,H)=13.2 Hz, 1H; ArCH2Ar), 3.06 (d, 2J
(H,H)=13.2 Hz, 2H;
ArCH2Ar), 3.11 (d, 2J
(H,H)=13.2 Hz, 1H; ArCH2Ar), 3.77–3.83 (m,
8H; OCH2), 3.91 (t, 3J
(H,H)=6.4 Hz, 4H; OCH2), 4.28–4.34 (m, 4H;
ArCH2Ar), 4.94–5.04 (m, 4H; CH=CH2), 5.76–5.86 (m, 2H; CH=CH2),
6.49 (dꢂd, 3J(H,H)=8.3 Hz, 4J
(H,H)=2.0 Hz, 2H; ArH), 6.74–6.81 (m,
ACHTNUGTERN(NUGN CH3)3), 1.45–1.52 (m, 4H; CH2), 1.66–1.73
(0.30, 89%) was obtained as a white crystalline powder. M.p. 290–2928C
1
(dec); H NMR (400 MHz, [D8]THF, 258C): d=0.48 (t, 3J
C
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
12H; CH3), 0.95 (m, 12H; TolCH3), 1.06–1.14 (m, 8H; CH2), 1.30 (s,
72H; C(CH3)3), 1.41 (m, 16H; CH2), 1.92 (m, 8H; CH2), 3.01–3.07 (m,
12H; ArCH2Ar, OCH2), 3.85 (m, 8H; OCH2), 4.43 (d, J
4H; ArCH2Ar), 6.80 (s, 8H; ArH), 7.35–7.37 (m, 24H; ArH), 7.45 (d,
2J
(H,H)=8.3 Hz, 16H; ArH), 7.56 (s, 4H; NH), 7.62 ppm (s, 4H; NH);
MS (ESI): m/z (%): calcd for C168H208N8O12: 2531.58; found: 2553.7 (38)
[M+Na]+, 1288.4 (100) [M+Na+H]2+
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
2
AHCTUNGTREGUN(NN H,H)=13.2 Hz,
A
ACHTUNGTRENNUNG
10H; ArH), 7.08–7.12 (m, 4H; ArH), 8.17 (s, 2H; NH), 8.29 (s, 2H;
NH), 8.75 ppm (brs, 2H; NH); MS (ESI): m/z (%): calcd for
C84H114N6O12: 1399.88; found: 1421.0 (100) [M+Na]+.
ACHTUNGTRENNUNG
.
5,11-BisACTHNUGRTENUNG[3,5-bis(4-tert-butylphenyl)-4-propoxyphenylureido]-17,23-bis[3-
(hex-5-enyloxy)phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene (21)
5,11,17-Tris[4-methylphenylureido]-23-[3,5-bis(4-tert-butylphenyl)-4-pro-
poxy-phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene (8): By follow-
ing the typical procedure for 1c, product 8 was formed (84%) as a white
powder by starting from the respective tritolyl urea.[24] M.p. 230–2338C
Boc deprotection: A solution of 20b (0.39 g, 0.28 mmol) and TFA (1 mL)
in CH2Cl2 (25 mL) was stirred for 2 h at room temperature. Then water
(10 mL) was added and the resulting organic layer was separated, washed
with a 10% aqueous solution of K2CO3 (2ꢂ10 mL) and with water (3ꢂ
10 mL), dried (MgSO4), and evaporated to give 5,11-diamino-17,23-bis-
[3-(hex-5-enyloxy)phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene
(0.31 g, 94%) as light-brown solid. M.p. 150–1558C (dec); 1H NMR
(400 MHz, [D8]THF, 258C): d=0.95 (m, 12H; CH3), 1.40 (m, 16H; CH2),
1.49–1.57 (m, 4H; CH2), 1.69–1.76 (m, 4H; CH2), 1.85–1.90 (m, 8H;
(dec); 1H NMR (400 MHz, [D6]DMSO, 258C): d=0.42 (t, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
AHCTUNGTRENGN(UN H,H)=
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
E
CH2), 2.06–2.11 (m, 4H; CH2), 2.50 (brs, 4H; NH2),2.81 (d, 2J
G
2
A
E
13.2 Hz, 1H; ArCH2Ar), 2.94 (d, J
(H,H)=13.2 Hz, 2H; ArCH2Ar), 3.03
3
2
U
(d, J
3J(H,H)=6.4 Hz, 4H; OCH2), 4.28 (d, 2J
ArCH2Ar), 4.34 (d, 2J
(H,H)=13.2 Hz, 2H; ArCH2Ar), 4.41 (d,
2J
(H,H)=13.2 Hz, 1H; ArCH2Ar), 4.90–5.01 (m, 4H; CH=CH2), 5.75–
5.85 (m, 2H; CH=CH2), 5.93–5.95 (m, 4H; ArH), 6.42 (dꢂd, 3J
(H,H)=
8.3,
4J
(H,H)=2.0 Hz, 2H; ArH), 6.50 (s, 2H; ArH), 6.77–6.79 (m, 4H; ArH),
7.01 (t, 3J
(H,H)=8.1 Hz, 2H; ArH), 7.25 (s, 2H; ArH), 7.42 (s, 2H;
ACHTUNGTRENNUNG
(m, 8H; ArH), 8.05 (s, 1H; NH), 8.17–8.19 (m, 4H; NH), 8.23 (s, 2H;
NH), 8.32 ppm (s, 1H; NH); MS (ESI): m/z (%): calcd for C102H124N8O9:
1606.17; found: 1628.9 (100) [M+Na]+.
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
5,17-Bis[4-methylphenylureido]-11,23-bisACHTNUGTRNEUNG[3,5-bis(4-tert-butylphenyl)-4-
propoxy-phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene (10): By
following the typical procedure described for 1c, product 10 was formed
(84%) by starting from the respective 1,3-ditolyl urea[25] as a white crys-
talline powder. M.p. 252–2558C (dec); 1H NMR (400 MHz, [D8]THF,
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
NH), 7.69 ppm (s, 2H; NH); MS (ESI): m/z (%): calcd for C74H98N6O8:
1199.64; found: 1221.7 (100) [M+Na]+.
258C): d=0.49 (t, 3J
12H; CH3), 1.07–1.16 (m, 4H; CH2), 1.32 (s, 36H; C
16H; CH2), 1.88–1.96 (m, 8H; CH2), 2.19 (s, 6H; TolCH3), 3.02–3.07 (m,
8H; ArCH2Ar, OCH2), 3.79 (t, 3J
(H,H)=7.6 Hz, 4H; OCH2), 3.92 (t,
3J(H,H)=7.6 Hz, 4H; OCH2), 4.43 (d, 2J
(H,H)=12.7 Hz, 4H;
ArCH2Ar), 6.68 (s, 4H; ArH), 6.91 (d, J(H,H)=8.3 Hz, 4H; TolH), 6.94
(s, 4H; ArH), 7.17 (d, 2J
(H,H)=8.3 Hz, 4H; TolH), 7.31 (s, 2H; NH),
7.38–7.40 (m, 12H; ArH), 7.46 (s, 2H; NH), 7.48 (d, 2J
(H,H)=8.3 Hz,
A
ACHTUNGTREN(NUNG H,H)=7.1 Hz,
G
Acylation: The diamino calix[4]arene (0.29 g, 0.24 mmol) was added to a
solution of freshly prepared isocyanate 18 (0.85 mmol) in toluene
(20 mL) under nitrogen. The reaction mixture was stirred overnight at
room temperature. Then methanol (50 mL) was added to the solution,
the formed precipitate was filtered off, washed with methanol, and dried
in air. Tetraurea 21 (0.48 g, 95%) was obtained as a white crystalline
powder. M.p. 282–2848C; 1H NMR (400 MHz, [D8]THF, 258C): d=0.49
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
2
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
8H; ArH), 7.64 (s, 2H; NH), 7.68 ppm (s, 2H; NH); MS (ESI): m/z (%):
(t, 3J
CH2), 1.33 (s, 36H; CAHCTUNGTRENNUNG
ACHTUNGTRENNUNG
calcd for C124H152N8O10: 1914.64; found: 1937.4 (100) [M+Na]+.
4H; CH2), 1.67–1.74 (m, 4H; CH2), 1.94 (m, 8H; CH2), 2.04–2.09 (m,
4H; CH2), 3.04–3.07 (m, 8H; ArCH2Ar, OCH2), 3.82–3.88 (m, 12H;
5,11-Bis(tert-butylcarbamoyl)-17,23-bis(4-methylphenylureido)-
25,26,27,28-tetrapentoxycalix[4]arene (20a): Tolyl isocyanate (0.17 g,
OCH2), 4.43 (d, 2J
ACHTUNGTRENNUNG
1.29 mmol) was added to
a
solution of diamino calix[4]arene 19[26]
AHCTUNGTRENNUNG
(0.42 g, 0.43 mmol) in dichloromethane (20 mL) and the mixture was
stirred at room temperature overnight. Then methanol (10 mL) was
added and the solvents were evaporated. The residue was treated with
acetonitrile (15 mL) and the resulting precipitate was filtered off and pu-
rified by column chromatography (THF/hexane 1:3) to give 20a (0.36 g,
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
NH), 7.59 ppm (s, 2H; NH); MS (ESI): m/z (%): calcd for C134H168N8O12
2082.88; found: 2105.4 (23) [M+Na]+.
:
68%) as
[D6]DMSO, 258C): d=0.93 (m, 12H; CH3), 1.37 (m, 34H; CH2, C-
(CH3)3), 1.89 (m, 8H; CH2), 2.21 (s, 6H; TolCH3), 3.05 (m, 4H;
ArCH2Ar), 3.80 (m, 8H; OCH2), 4.31 (m, 4H; ArCH2Ar), 6.78 (m, 8H;
ArH), 7.03 (d, 3J(H,H)=8.3 Hz, 4H; TolH), 7.25 (d, 3J
(H,H)=8.3 Hz,
a
white powder. M.p. 187–1908C; 1H NMR (400 MHz,
5,11-Bis(4-methylphenylureido)-17,23-bisACHTNUGTRNEUNG[3,5-bis(4-tert-butylphenyl)-4-
T
propoxy-phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene (9): This
product was prepared from 20a by following the typical procedure de-
scribed for 21.
A
ACHTUNGTRENNUNG
4H; TolH), 8.14 (s, 2H; NH), 8.18 (s, 2H; NH), 8.76 ppm (brs, 2H; NH);
MS (ESI): m/z (%): calcd for C74H98N6O10: 1231.64; found: 1253.8 (100)
[M+Na]+, 2485.5 (23) [2M+Na]+.
Boc
deprotection:
5,11-Diamino-17,23-bis-(4-metyl-phenylureido)-
25,26,27,28-tetrapentoxy-calix[4]arene (90%) was obtained as a brownish
powder. M.p. 190–1958C (dec); 1H NMR (400 MHz, [D6]DMSO, 258C):
5,11-Bis(tert-butylcarbamoyl)-17,23-bis[3-(hex-5-enyloxy)phenylureido]-
25,26,27,28-tetrapentoxycalix[4]arene (20b): A solution of diamino cal-
d=0.92 (t, 3J
ACTHUNGTERN(UNG H,H)=7.0 Hz, 12H; CH3), 1.37 (m, 16H; CH2), 1.87 (m,
8H; CH2), 2.22 (s, 6H; TolCH3), 2.80 (d, 2J
ACTHNUTRGNE(NUG H,H)=12.4 Hz, 1H;
Chem. Eur. J. 2010, 16, 4541 – 4549
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4547

V. Bçhmer, Y. Rudzevich, and V. Rudzevich
ArCH2Ar), 2.94 (d, 2J
2J
(H,H)=12.8 Hz, 1H; ArCH2Ar), 3.69 (m, 4H; OCH2), 3.79 (m, 4H;
OCH2), 4.16 (d, 2J(H,H)=12.4 Hz, 1H; ArCH2Ar), 4.25 (d, 2J
(H,H)=
12.8 Hz, 2H; ArCH2Ar), 4.31 (brs, 4H; NH2), 4.33 (d, J(H,H)=12.8 Hz,
(H,H)=2.4 Hz, 2H; ArH),
(H,H)=2.4 Hz, 2H; ArH), 7.04 (d, 3J
(H,H)=8.2 Hz, 4H;
TolH), 7.26 (d, 3J
(H,H)=8.2 Hz, 4H; TolH), 8.16 (s, 2H; NH), 8.23 ppm
G
(m, 12H; CH3), 1.06–1.11 (m, 6H; CH2), 1.30 (s, 54H; C
16H; CH2), 1.89 (brs, 8H; CH2), 2.16 (s, 3H; TolCH3), 3.05–3.12 (m,
10H; OCH2, ArCH2Ar), 3.82–3.90 (m, 8H; OCH2), 4.38 (d, 2J
(H,H)=
12.7 Hz, 4H; ArCH2Ar), 6.75 (s, 2H; ArH), 6.77 (s, 2H; ArH), 6.80 (d,
4J(H,H)=2.0 Hz, 2H; ArH), 6.85 (d, 4J
(H,H)=2.0 Hz, 2H; ArH), 6.90
(d, 3J(H,H)=8.3 Hz, 2H; TolH), 7.17 (d, 3J
(H,H)=8.3 Hz, 2H; TolH),
7.28 (s, 2H; ArH), 7.29 (s, 4H; ArH), 7.39–7.46 (m, 24H; ArH), 7.92 (s,
1H; NH), 8.00 (s, 1H; NH), 8.03 (s, 3H; NH), 8.18 ppm (s, 3H; NH);
MS (ESI): m/z (%): calcd for C146H180N8O11: 2223.11; found: 2245.4 (100)
[M+Na]+.
ACHTUGNTREN(UNNG CH3)3), 1.41 (m,
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
G
G
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
(s, 2H; NH); MS (ESI): m/z (%): calcd for C64H82N6O6: 1031.40; found:
1053.8 (100) [M+Na]+, 2085.2 (12) [2M+Na]+.
Acylation: Tetraurea 9 (84%) was obtained as a beige solid. M.p. 290–
2928C; 1H NMR (400 MHz, [D6]DMSO, 758C): d=0.45 (t, 3J
ACHTUNGTRENNUNG
7.2 Hz, 6H; CH3), 0.95 (t, 3J
CH2), 1.33 (s, 36H; C
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
A
ACHTUNGTREN(NUGN H,H)=7.2 Hz, 8H; OCH2),
A
Acknowledgements
3
3
ACHUTNGREN(NUG H,H)=8.1 Hz, 4H; TolH), 7.19 (d, JACHTUGNTREN(NUGN H,H)=
8.1 Hz, 4H; TolH), 7.29 (s, 4H; ArH), 7.44 (m, 16H; ArH), 7.92 (s, 2H;
NH), 8.01 (s, 2H; NH), 8.04 (s, 2H; NH), 8.18 ppm (s, 2H; NH); MS
(ESI): m/z (%): calcd for C102H124N8O9: 1914.64; found: 980.1 (21)
[M+Na+H]2+, 1937.2 (100) [M+Na]+.
This work was supported by the Deutsche Forschungsgemeinschaft (Bo
523/14-4, SFB 625). The authors thank Dr. A. Bogdan (Johannes Guten-
berg-Universitꢀt Mainz) for samples of compounds 1b, 3b, and 12.
Monoloop calix[4]arene 3c:
A solution of tetraurea 21 (0.47 g,
[1] For recent examples, see: a) K. Nakabayashi, Y. Ozaki, M. Kawano,
M. Fujita, Angew. Chem. 2008, 120, 2076–2078; Angew. Chem. Int.
Ed. 2008, 47, 2046–2048; b) I. M. Mꢄller, D. Mçller, C. A. Schalley,
Angew. Chem. 2005, 117, 485–488; Angew. Chem. Int. Ed. 2005, 44,
480–484; c) P. S. Mukherjee, N. Das, P. J. Stang, J. Org. Chem. 2004,
69, 3526–3529; d) K. Suzuki, M. Kawano, S. Sato, M. Fujita, J. Am.
Chem. Soc. 2007, 129, 10652–10653; e) S. Sato, J. Iida, K. Suzuki, M.
Kawano, T. Ozeki, M. Fujita, Science 2006, 313, 1273–1276; f) K.
Ghosh, H.-B. Yang, B. H. Northrop, M. M. Lyndon, Y.-R. Zheng,
D. C. Muddiman, P. J. Stang, J. Am. Chem. Soc. 2008, 130, 5320–
5334; g) K. C.-F. Leung, F. Aricꢅ, S. J. Cantrill, J. F. Stoddart, Macro-
molecules 2007, 40, 3951–3959; h) F. Huang, D. S. Nagvekar, C. Sle-
bodnick, H. W. Gibson, J. Am. Chem. Soc. 2005, 127, 484–485.
[2] a) J. Rebek, Jr., Chem. Commun. 2000, 637–643; b) K. D. Shimizu,
J. Rebek, Jr., Proc. Nat. Acad. Sci. USA 1995, 92, 12403–12407;
c) B. C. Hamann, K. D. Shimizu, J. Rebek, Jr., Angew. Chem. 1996,
108, 1425–1427; Angew. Chem. Int. Ed. Engl. 1996, 35, 1326–1329.
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2008, 14, 3346–3354; b) O. Molokanova, A. Bogdan, M. O. Vysot-
sky, M. Bolte, T. Ikai, Y. Okamoto, V. Bçhmer, Chem. Eur. J. 2007,
13, 6157–6170; c) A. Bogdan, M. O. Vysotsky, L. Wang, V. Bçhmer,
Chem. Commun. 2004, 1268–1269.
[4] A. Bogdan, M. O. Vysotsky, T. Ikai, Y. Okamoto, V. Bçhmer, Chem.
Eur. J. 2004, 10, 3324–3330.
[5] a) C. Gaeta, M. O. Vysotsky, A. Bogdan, V. Bçhmer, J. Am. Chem.
Soc. 2005, 127, 13136–13137; b) O. Molokanova, M. O. Vysotsky, Y.
Cao, I. Thondorf, V. Bçhmer, Angew. Chem. 2006, 118, 8220–8224;
Angew. Chem. Int. Ed. 2006, 45, 8051–8055.
[6] R. K. Castellano, D. M. Rudkevich, J. Rebek, Jr., Proc. Nat. Acad.
Sci. USA 1997, 94, 7132–7137.
[7] R. K. Castellano, J. Rebek, Jr., J. Am. Chem. Soc. 1998, 120, 3657–
3663.
0.23 mmol) and tetratosyl urea 2 (0.36 g, 0.25 mmol) in CH2Cl2/benzene
2:1 (450 mL) was stirred for 12 h at room temperature. Then nitrogen
was bubbled through the solution for 1 h, Grubbsꢃs catalyst (1st genera-
tion; 0.037 g, 0.045 mmol) was added and the stirring was continued for
2 days. After the addition of Et3N (1.5 mL), the reaction mixture was
stirred for 1 h and then the solvents were evaporated. The residue was
purified by column chromatography (ethyl acetate/hexane 1:3 followed
by 1:1). The white solid obtained after evaporation was dissolved in THF
(25 mL) and hydrogenated over 6 h at room temperature in the presence
of the Pt2O (0.05 g). The catalyst was filtered and the solvent was evapo-
rated. The residue was reprecipitated with methanol from CHCl3/acetone
solution to give 3c (0.28 g, 54%) as a white powder. M.p. 258–2608C
1
(dec); H NMR (400 MHz, [D8]THF, 258C): d=0.49 (t, 3J
A
6H; CH3), 0.96 (m, 12H; CH3), 1.07–1.16 (m, 4H; CH2), 1.32 (s, 44H; C-
(CH3)3, CH2), 1.42–1.46 (m, 16H; CH2), 1.68–1.74 (m, 8H; CH2), 1.94 (m,
8H; CH2), 3.03–3.08 (m, 8H; ArCH2Ar, OCH2), 3.83–3.88 (m, 12H;
ACHTUNGTRENNUNG
2
3
OCH2), 4.43 (d, J
8.3, 4J
(H,H)=2.0 Hz, 2H; ArH), 6.65–6.70 (m, 4H; ArH), 6.80–6.84 (m,
6H; ArH), 6.92 (d, 4J
(H,H)=2.0 Hz, 2H; ArH), 7.15 (s, 2H; ArH), 7.33
(s, 4H; ArH), 7.39 (d, 3J(H,H)=8.3 Hz, 8H; ArH), 7.48 (d, 3J
(H,H)=
ACHTUNGTRENNUNG(H,H)=13.2 Hz, 4H; ArCH2Ar), 6.30 (dꢂd, JACHUTNGTREN(NUGN H,H)=
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
8.3 Hz, 8H; ArH), 7.50 (s, 2H; NH), 7.52 (s, 4H; NH), 7.61 ppm (s, 2H;
NH); MS (ESI): m/z (%): calcd for C132H166N8O12: 2056.84; found: 2079.2
(100) [M+Na]+.
5-Amino-11,17,23-trisACHTUNGTRENNUNG[3,5-bis(4-tert-butylphenyl)-4-propoxyphenylurei-
do]-25,26,27,28-tetrapentoxycalix[4]arene (24): A solution of tetraamino
calix[4]arene 23[30] (0.10 g, 0.13 mmol), active urethane 17 (0.34 g,
0.59 mmol), and Et3N (0.2 mL) in CHCl3 (15 mL) was refluxed for
2 days. The solvent was evaporated and the residue was triturated with
MeOH (50 mL). The formed precipitate was filtered off and dried in air.
Calix[4]arene 24 (0.20 g, 73%) was obtained as a pale-brown powder.
M.p. 237–2398C; 1H NMR (400 MHz, [D6]DMSO, 1008C): d=0.42–0.47
(m, 9H; CH3), 0.94 (m, 12H; CH3), 1.06–1.13 (m, 6H; CH2), 1.32 (s,
[8] a) Y. Rudzevich, V. Rudzevich, C. Moon, I. Schnell, K. Fischer, V.
Bçhmer, J. Am. Chem. Soc. 2005, 127, 14168–14169; b) Y. Rudze-
vich, V. Rudzevich, C. Moon, G. Brunklaus, V. Bçhmer, Org.
Biomol. Chem. 2008, 6, 2270–2275.
[9] The formation of heterodimers was initially even considered as an
additional proof for the dimerization: O. Mogck, V. Bçhmer, W.
Vogt, Tetrahedron 1996, 52, 8489–8496.
[10] R. K. Castellano, B. H. Kim, J. Rebek, Jr., J. Am. Chem. Soc. 1997,
119, 12671–12672.
[11] For examples involving “rigid” bisACTHUNRGTNE(NUG crown-3) derivatives, see: Y.
54H; C
2J
(H,H)=13.2 Hz, 2H; ArCH2Ar), 3.07–3.13 (m, 8H; OCH2, ArCH2Ar),
3.78–3.91 (m, 8H; OCH2), 3.98 (brs, 2H; NH2), 4.32 (d, 2J
(H,H)=
(H,H)=13.2 Hz, 2H; ArCH2Ar), 6.01
(H,H)=2.4 Hz, 2H; ArH), 6.77 (s, 2H; ArH),
(H,H)=2.4 Hz, 2H; ArH), 7.29 (s, 4H; ArH), 7.32 (s, 2H;
ACHTUNGTRENNUNG(CH3)3), 1.41 (m, 16H; CH2), 1.87 (m, 8H; CH2), 2.97 (d,
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
2
13.2 Hz, 2H; ArCH2Ar), 4.39 (d, J
(s, 2H; ArH), 6.72 (d, 4J
6.81 (d, 4J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ArH), 7.39–7.50 (m, 24H; ArH), 7.89 (s, 2H; NH), 8.00 (s, 1H; NH),
8.08 (s, 1H; NH), 8.11 ppm (s, 2H; NH); MS (ESI): m/z (%): calcd for
C138H173N7O10: 2089.96; found: 2112.4 (100) [M+Na]+.
5-[4-Methylphenylureido]-11,17,23-trisACTHNUGRTNEUNG[3,5-bis(4-tert-butylphenyl)-4-pro-
Rudzevich, M. O. Vysotsky, V. Bçhmer, M. S. Brody, J. Rebek, Jr.,
F. Broda, I. Thondorf, Org. Biomol. Chem. 2004, 2, 3080–3084.
[12] M. Bolte, I. Thondorf, V. Bçhmer, V. Rudzevich, Y. Rudzevich,
CrystEngComm 2008, 10, 270–272; see also: G.-K. Li, Y. Yang, C.-F.
Chen, Z.-T. Huang, Tetrahedron Lett. 2007, 48, 6096–6099.
poxy-phenylureido]-25,26,27,28-tetrapentoxycalix[4]arene (11): By start-
ing from the tri-urea 24 and tolyl isocyanate, the typical procedure de-
scribed for 1c produced 8 (76%) as a white powder. M.p. 269–2708C;
1H NMR (400 MHz, [D6]DMSO, 758C): d=0.41–0.46 (m, 9H; CH3), 0.94
4548
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Chem. Eur. J. 2010, 16, 4541 – 4549

Fine-Tuning the Dimerization of Tetraureacalix[4]arenes
FULL PAPER
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zevich, V. Bçhmer, Synlett 2009, 1887–1904.
[15] The attachment to the meta-position allows the symmetrical con-
struction of adjacent loops up to the tetraloop derivatives.
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[17] The heterodimer 1d·7c was finally formed in two weeks after
mixing.
[18] It is not even necessary that all calixarenes are mixed in stoichio-
metric amounts, as only the respective pairs must be present in the
same quantities.
[19] Statistically seven tetraureas (1a–d, 7a–c) allow 28 combinations,
among which six are impossible due to an overlap of loops, and an
additional six are also impossible due to their bulky residue(s),
which cannot pass the loop(s).
idues R (Scheme 1). Due to the strong hydrogen bonding formed
with the C=O oxygen of the adjacent urea function these resonances
are shifted to the low field of the spectrum and can be observed
aside from other signals.
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[21] The remaining two urea residues of the monoloop compound must
bear bulky substituents. Otherwise it can also build a homodimer.
[22] Even after one month the heterodimer cannot be detected.
[23] One of the main characteristics of the dimers of type 1·1 are the res-
onances corresponding to the NHa protons, attached to the urea res-
Received: January 6, 2010
Published online: March 12, 2010
Chem. Eur. J. 2010, 16, 4541 – 4549
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4549