Hydrogen bonding in dimers of tritolyl and tritosylurea derivatives of triphenylmethanes

Article abstract of DOI:10.1039/b609707c

The crystal structure of the homodimer formed by the tritolylurea 3a proves the existence of a belt of six bifurcated hydrogen bonds between both NH and the OC groups of the adjacent urea residues. For the tritosylurea 3b, four additional three-center hydrogen bonds, also involving the SO₂ oxygen, are found in the crystalline state. Molecular dynamics simulations in a chloroform box confirm these patterns of the hydrogen bonds and the resulting elongation of the dimer 3b·3b in comparison to 3a·3a. The calculated complexation energies for the three dimeric combinations are nearly identical in agreement with the simultaneous formation of heterodimer 3a·3b in a mixture of 3a and 3b. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b609707c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Hydrogen bonding in dimers of tritolyl and tritosylurea derivatives of
triphenylmethanes†
Yuliya Rudzevich,a Valentyn Rudzevich,‡a Dieter Schollmeyer,b Iris Thondorfc and Volker Bo¨hmer*a
Received 7th July 2006, Accepted 18th August 2006
First published as an Advance Article on the web 5th September 2006
DOI: 10.1039/b609707c
The crystal structure of the homodimer formed by the tritolylurea 3a proves the existence of a belt of
=
six bifurcated hydrogen bonds between both NH and the O C groups of the adjacent urea residues.
For the tritosylurea 3b, four additional three-center hydrogen bonds, also involving the SO2 oxygen, are
found in the crystalline state. Molecular dynamics simulations in a chloroform box confirm these
patterns of the hydrogen bonds and the resulting elongation of the dimer 3b·3b in comparison to 3a·3a.
The calculated complexation energies for the three dimeric combinations are nearly identical in
agreement with the simultaneous formation of heterodimer 3a·3b in a mixture of 3a and 3b.
acidity of –SO2–NH– and the basicity of the urea carbonyl group
Introduction
has been tentatively suggested, but the different geometry of
The key factor for the dimerisation of calix[4]arene derivatives
the two urea groups seems to be also important. The two X-
1, substituted at their wide rim by four urea functions, is the
= =
ray structures reported for tosylureas reveal that the O S O
oxygen can also act as a hydrogen bond acceptor.11 Numerous
attempts to obtain single crystals of a homodimer 1b·1b or
even of a heterodimer 1a·1b failed so far. Recently, we could
show12,13 that triarylurea derivatives of triphenylmethanes 2a form
hydrogen bonded dimers, as well as their tosylurea counterparts
2b. Heterodimers 2a·2b are also observed in this case, though not
exclusively.
formation of a belt of intermolecular hydrogen bonds between
their urea functions.1 The structure of these dimeric capsules,
initially deduced from their H NMR spectra,2 was confirmed
1
for the solid state by several X-ray structures.3 This dimerisa-
tion is not only interesting for the inclusion of guests.4 It has
been used also to build up larger polymeric structures via self-
assembly processes.5 In this regard, it is of great importance that
tetraaryl (1a) and tetraarylsulfonylurea derivatives (1b) combine
exclusively to heterodimers in a stoichiometric mixture, although
both form homodimers when dissolved alone.6 This serendipitous
observation was the basis for the construction of alternating (∼A–
AB–BA–A∼) or directional (∼A–BA–BA–B∼) polymers from
“monomeric” bis-tetraurea units (A–A/B–B or A–B), in which
two calix[4]arenes are covalently linked via their narrow rim.7
It also enabled the construction of well-defined structures with
three7 or four8 dimeric/capsular substructures, as well as the self-
assembly of structurally uniform dendrimers9 with molar masses
up to 25 000. Tetraarylsulfonylureas 1b have been successfully used
also as template in the synthesis of bis- or tetraloop tetraureas
by metathesis,10 since four or eight alkenyl groups attached to a
tetraarylurea 1 are perfectly prearranged for their intramolecular
connection within its heterodimer with a tetratosylurea 1b.
We were able, however, to obtain single crystals from homo-
dimers of a similar triurea 3a·3a and 3b·3b, which are described
subsequently, and discussed together with MD-simulations on
these systems. The dimerisation studies were extended also to
further triureas of type 3.
In spite of its frequent use, the reason for this pronounced
selectivity, which is not found for alkyl as opposed to arylureas,
is not exactly known. A favorable combination of the increased
aAbteilung Lehramt Chemie, Fachbereich Chemie, Pharmazie und Geowis-
senschaften, Johannes Gutenberg-Universita¨t Mainz, Duesbergweg 10-14,
D-55099, Mainz, Germany. E-mail: vboehmer@uni-mainz.de
Results and discussion
bInstitut fu¨r Organische Chemie, Johannes Gutenberg-Universita¨t Mainz,
Duesbergweg 10-14, D-55099, Mainz, Germany
Synthesis and dimerisation
cFachbereich Biochemie/Biotechnologie, Institut fu¨r Biochemie, Martin-
Luther-Universita¨t Halle-Wittenberg, Kurt-Mothes-Str. 3, D-06099, Halle,
Germany
† Electronic supplementary information (ESI) available: NMR spectra of
3a–e in CDCl3 and DMSO-d6. See DOI: 10.1039/b609707c
Triurea derivatives 3a–c were prepared as usual by reaction of the
corresponding triamine14 with the respective isocyanates.
In contrast to the analogous calix[4]arenes, the 1 : 1 mixture of 3a
and 3b did not lead to the exclusive formation of the heterodimer
3a·3b in apolar solvents (chloroform, dichloromethane, tetra-
chloroethane, benzene), but to a mixture of the two homodimers
‡ Permanent address: Institute of Organic Chemistry, NAS of Ukraine,
Murmanska str. 5, 02094, Kyiv-94, Ukraine
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and the heterodimer in a (nearly statistical) ratio 1 : 1 : 1 (Fig. 1).
See the ESI for full NMR data.†
Crystal structures
Single crystals of 3a and 3b were obtained by slow diffusion of
hexane into a solution in chloroform.§ Although the space group
is different (C2/c for 3a, P1- for 3b), both form similar hydrogen
bonded dimers in which the two molecules are related by a centre
of symmetry (Fig. 2).
The shape of the triphenyl methane skeleton shows stronger
deviations from a threefold symmetry for 3b than for 3a, as
revealed by stronger deviations from a regular triangle for the
phenolic oxygens and the methyl carbons. This is compensated
by stronger differences between the dihedral angles of the three
phenyl rings, and the triangle of the nitrogen atoms attached to
trityl is (necessarily) close to “regular” (compare Table 1).
Both dimers are held together by a closed belt of intermolecular
hydrogen bonds between the (sulfonyl)urea of the opposite
molecules (Fig. 2). For 3a, bifurcated hydrogen bonds between
Fig. 1 Sections of the 1H NMR spectra (400 MHz, CDCl3) of 3a (a), 3b
(b) and of their stoichiometric mixture (c). The signals for the heterodimer
are shown in green.
The phosphorylurea derivative 3c was synthesized to complete
the picture, since the corresponding tetraurea 1c formed exlusively
heterodimers 1a·1c, although neither homodimers 1c·1c nor
heterodimers 1b·1c were observed. In the case of the triureas,
however, no dimerisation at all was found for 3c.
No heterodimerisation was observed for the 3,5-m-substituted
derivatives 3d,e, even not with a tenfold excess of the tritosylurea
3b, although homodimers are readily and quantitatively formed.
This makes the initially-intended synthesis of multi-macrocycles
via intramolecular olefin metathesis of 3e impossible, which it was
easily performed in the case of tetraurea calix[4]arenes.
=
C O as acceptor and both NH as donor are found, like in dimers
of tetraurea calix[4]arenes. However, in contrast to the calixarenes,
the hydrogen bond formed by the tolyl–NH is weaker, as evidenced
by a longer NH · · · O and N · · · O distance. The angle between
§ CCDC reference numbers 614133–614134. For crystallographic data in
CIF format see DOI: 10.1039/b609707c
Fig. 2 Molecular conformation of dimers 3a·3a (top) and 3b·3b (bottom), seen from the side (a) and from the top (b) and schematic description of the
˚
=
=
hydrogen bonding systems (c) (distances NH · · · O C and NH · · · O S in A). Hydrogen atoms and pentyl substituents are omitted for clarity. Top views
are obtained from the side views by 90◦ rotation around a horizontal axis.
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Table 1 Selected geometrical parameters for the molecules 3a and 3b
Parameter
3a
3b
Angles in the triangles of, (deg)
Phenyl oxygens
62.98, 57.24, 59.79
61.05, 57.32, 61.63
58.47, 58.96, 62.56
59.27, 59.48, 61.24
60.28, 66.53, 53.18
60.81, 64.17, 55.01
58.93, 61.88, 59.19
61.15, 60.95, 57.91
Methyl carbons attached to trityl
Nitrogens attached to trityl
Nitrogens attached to tolyl or tosyl
Interplanar angles of, (deg)a
{Aryl}/{Aryl}
82.13, 78.40, 78.31
49.85, 51.00, 56.51
80.10, 70.39, 77.92
78.57, 88.85, 77.08
53.80, 50.13, 61.66
72.65, 78.88, 63.07
{Aryl}/attached {Urea}
ꢀ
{Urea}/H-bonded {Urea}
˚
Distances between planes, (A)
Carbons substituted by urea
Nitrogens attached to trityl
Urea oxygens
4.095
1.651
4.934
2.490
0.573
−1.777
−0.036
Nitrogens attached to tolyl or tosyl
−2.452
a
{Aryl}—best planes through the carbons of the trityl phenyl rings; {Urea}—best planes through N–CO–N groups.
hydrogen bonded urea groups (best plane through two N, C and O)
is in the range of 70–80◦ for 3a while it was 84◦ for a dimer of a
tetraurea calix[4]arene (1a with Y = CH2COOEt).3 A stronger
difference is found for the angles between aromatic planes of the
trityl skeleton and the urea attached to it. They are 8–9◦ for 1a
and 50–57◦ for 3a.
3a·3b in a box of chloroform molecules. In all starting structures
the monomers were arranged to form a bifurcated hydrogen bond-
ing pattern involving only the urea groups. This structure persisted
on the MD timescale for 3a·3a. The dimers with tosyl units
rearranged to form hydrogen bonding patterns different from the
starting one during the first nanoseconds of the simulation.
In principle, 12 bifurcated hydrogen bonds could be formed in
3a·3a, 18 in 3b·3b (bifurcated, three centered) and 15 in 3a·3b
(compare Scheme 1). Averaging over the simulation time revealed
that 8.7, 12.1 and 9.8 hydrogen bonds were present in 3a·3a, 3b·3b
and 3a·3b, respectively, albeit with different strengths and different
occupancies (cf., Table 2). Like in the crystal, in the homodimer
3a·3a the trityl–NH formed stronger hydrogen bonds than the NH
attached to the tolyl rings. Generally, the structure averaged over
the 9 ns MD simulations very closely resembles the X-ray structure
(rms deviation of the heavy atoms of the trityl units and the urea
=
For 3b the situation is slightly more complex. All C O groups
are acceptors for such bifurcated hydrogen bonds, and in two cases
(O5, O6) the more acidic tosyl–NH forms the stronger hydrogen
bond according to the shorter distance, while for O4 the trityl–
NH is the stronger bound. In the former two cases the trityl–NH
is involved in three-centered hydrogen bonds involving also the
oxygen (O9, O12) of the adjacent SO2 group as acceptor. The
sulfonyl group of S1 is not involved in hydrogen bonding (Fig. 2).
This is expressed already by a torsion angle S1–N2–C9–O4 = −33◦
(compared to −11 and 2◦ for the two other groups), which turns
it away from the corresponding urea function. Similar to 3a the
angles between hydrogen bonded urea groups are 63–79◦ for 3b
and those between urea and aryl planes 50–62◦.
˚
functions 0.25 A).
In contrast, the homodimer 3b·3b was characterized by a strong
hydrogen bond between the tosyl–NH and the carbonyl oxygen of
˚
The difference in the hydrogen bonding, involving also the SO2-
groups in 3b, leads to a significant elongation of the dimer. The
the adjacent urea group (dNH · · · O = 2.01 A) which is present in 87%
of the snapshots. Weaker hydrogen bonds were formed between
˚
˚
=
=
distance between the methin carbon atoms is 8.13 A in 3a vs 9.03 A
in 3b. Similarly the enlargement can be expressed by the distance
between various reference planes (carbons substituted by urea,
urea nitrogens (N1, N3, N5 and N2, N4, N6) or oxygens (O4, O5,
O6), see Table 1.
the trityl–NH and the C O and S O groups which in turn were
also less frequently detected during the simulations (55 and 57%
of all snapshots, respectively). This observed hydrogen bonding
pattern (schematically shown in Scheme 1) is commensurate with
the overall picture provided by the X-ray structure of 3b·3b
(superposition of the heavy atoms of the trityl residues and the
urea functions of the X-ray structure and the average MD structure
Molecular dynamics simulations
˚
yielded a rms deviation of 0.29 A). The involvement of the tosyl–
NH protons in the strongest hydrogen bond and the formation of a
MD simulations using the Amber7 program were performed for
=
NH · · · O S hydrogen bond are the reasons for the enlargement of
the homodimers 3a·3a and 3b·3b as well as for the heterodimer
Scheme 1 Hydrogen bonding pattern of the dimers observed in the MD simulations. Strong hydrogen bonds are labelled by thick dashed lines.
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Table 2 Average geometric parameters obtained from the MD simula-
Judging from the number and strengths of hydrogen bonds
per monomeric unit the formation of the heterodimer should
˚
tions (all distances in A)
be slightly favoured over the two homodimers (DEi
=
Parameter
3a·3a
3b·3b
3a·3b
−236.0 kcal mol−1 vs −228.3 kcal mol−1, cf. Table 3). However,
the monomeric units are slightly more strained in 3a·3b and the
difference of the complexation energies (DEc = −93.4 kcal mol−1
vs −92.7 kcal mol−1) is insignificant. This is in agreement with
the simultaneous formation of homo- and heterodimers from a
mixture of 3a and 3b.
General
Number of H-bondsa 8.7
12.1
9.8
b
dC · · · C
8.05 0.28
9.25 0.26
4.50 0.07
4.18 0.22
4.39 0.21
9.46 0.33
4.43 0.08
4.15 0.25
4.11 0.25
4.60 0.15
c
rgyr
4.59 0.07
4.22 0.24
4.47 0.21
d
dO · · · O
e
dCO · · · CO
=
Trityl NH · · · O
C
dNH · · · O
1.98 0.21
88%
2.48 0.50
55%
1.97 0.18g
3.30 0.67h
96%g/10%h
Conclusions
Observedf
Like the tetratolylurea calix[4]arene dimers 1a·1a the tritolylurea
dimers 3a·3a are held together by bifurcated hydrogen bonds
=
C
Tol or Tos NH · · · O
dNH · · · O
2.41 0.35
57%
2.01 0.24
87%
2.05 0.19g
2.46 0.40h
90%g/30%h
=
between NH– and O C-groups. However, the crystal structure of
Observed
3a·3a reveals small geometrical differences (distances, interplanar
angles aryl–urea and urea–urea). The crystal structure of 3b·3b
proves that three-center hydrogen bonds involving the SO2-groups
are additionally formed in the tritosylurea dimers. Molecular
dynamics simulations for both dimers are in close agreement with
these results, predicting also correctly the elongation of the dimer,
due to the different hydrogen bonding pattern. They do not suggest
significant differences for the complexation energies of the three
possible dimeric combinations 3a·3a, 3a·3b and 3b·3b which again
is in agreement with the simultaneous observation of homo- and
heterodimers.
=
S
Trityl NH · · · O
dNH · · · O
2.39 0.42
57%
2.11 0.68
75%
Observed
=
Tol NH · · · O
S
dNH · · · O
3.81 0.57
3%
3.10 0.93
25%
Observed
a Number of H-bonds between the monomeric units, distance and angle
◦
criterion 2.75 A and 135 , respectively. b Distance of the methine carbon
atoms. c Radius of gyration of the carbonyl groups. d Intramolecular
distance of the ether oxygen atoms. e Intermolecular distance of adjacent
carbonyl carbon atoms. f Percentage of the snapshots in which this H-bond
was observed. g Tritosylurea. h Tritolylurea.
˚
It is reasonable to assume that analogous patterns with a
combination of bifurcated and three center hydrogen bonds are
present in tetraurea dimers involving the tetratosylurea 1b. Due
to geometrical differences between the calix[4]arene and the trityl
skeleton they may lead to an energy gain for the heterodimer
1a·1b which then would explain its exclusive formation in a
stoichiometric mixture of 1a and 1b.
the dimer along the axis defined by the two methine carbons (the
˚
S3 axis) by more than 1 A compared to the dimer 3a·3a (Table 2).
In the heterodimer 3a·3b the tosylureas formed strong bifur-
˚
cated hydrogen bonds (dNH · · · O = 1.98/2.05 A, occupancy 96
=
and 90%, respectively). In contrast to 3b·3b, the O S group
˚
is also involved in a strong hydrogen bond (dNH · · · O = 2.11 A,
Experimental
occupancy 75%) to the trityl–NH while the tolyl–NH formed
=
weaker hydrogen bonds to O C (Scheme 1). In 25% of all
snapshots even a hydrogen bond is formed between the tolyl–
Synthesis of compounds
Melting points are uncorrected. 1H, 13C and 31P nuclear magnetic
resonance spectra were recorded on a Bruker Avance DRX 400
spectrometer at 400, 100.6 and 162 MHz, respectively. Chemical
shifts were reported in d units (ppm) with reference to the residual
solvent peaks, and J values are given in Hz. Decoupling and
DEPT experiments confirmed the assignments of the signals. ESI
mass spectra were recorded on a Waters/Micromass QTof Ultima
3 mass spectrometer. All solvents were HPLC grade and used
without further purification. The isocyanates were purchased from
Aldrich or Acros.
=
NH and O S (not shown in Scheme 1). As a consequence of this
hydrogen bonding pattern the dimer 3a·3b exhibits an even larger
extension along the S3 axis as 3b·3b (Table 2).
It is interesting to note that the dimers 3a·3a and 3a·3b
experience an additional stabilization by intermolecular CH · · · p
contacts between the methyl groups attached to the trityl residues
and the adjacent tolyl rings (average distances between the methyl
carbon and the centroid of the aromatic ring 3.94 and 4.58 A,
respectively)15 while this arrangement is not possible for the tosyl
˚
residues due to their bent structure.
Table 3 Average energy componentsa for the dimers of 3a and 3b
Dimer
E1
E2
DEi
DEs
DEc
3a·3a
3b·3b
3a·3b
−145.5 7.3
−419.6 8.3
−144.5 7.3
−145.4 7.3
−419.3 8.4
−417.4 8.4
−94.8 3.4
−385.6 10.6
−972.5 10.5
−679.9 11.1
−41.5 9.3
−51.2 9.4
−46.7 8.0
−133.5 7.6
−118.0 6.2
a E1, E2: energies of the two monomeric units within the assembly, the energies of the free monomeric units are E3a = 151.3 7.6 kcal mol−1, E3b
=
435.1 7.9 kcal mol−1; Ei: interaction energy between the two monomeric units; Es: steric energy of the assembly = E1 + E2 + Ei; Ec: complexation
energy per monomeric unit = 0.5 × (Es–E1,free–E2,free).
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Tris(2-pentoxy-3-methyl-5-p-tolylureidophenyl)methane
(3a).
OCH2), 6.16 (3H, d, 4J = 2 Hz, ArH), 6.78 (1H, s, Ar3CH), 6.88
(3H, d, 4J = 2 Hz, ArH), 7.12 (6H, d, 3J = 8.2 Hz, ArHTos ), 7.39
(3H, s, NH), 7.61 (6H, d, 3J = 8.2 Hz, ArHTos ), 8.87 (3H, s, NH);
13C NMR (100.6 MHz, CDCl3), d: 14.1 (CH2CH3), 16.8 (ArCH3),
21.6 (ArCH3), 22.7 (CH2), 28.2 (CH2), 29.9 (CH2), 36.5 (Ar3CH),
72.4 (OCH2), 124.2 (CHAr), 127.8 (CHAr), 128.0 (CHTos ), 129.0
(CAr), 129.4 (CHTos ), 133.3 (CAr), 136.5 (CAr), 136.9 (CAr), 144.0
(CAr), 152.9 (CAr), 154.2 (C(O)).
Tolyl isocyanate (0.4 g, 3.05 mmol) was added to the solution
of tris(2-pentoxy-3-methyl-5-aminophenyl)methane14 (0.3 g,
0.51 mmol) in methylene chloride (10 mL). The reaction mixture
was diluted with methanol (30 mL) after stirring for 12 h. The
formed precipitate was filtered off and dried on the air to give
compound 3a (0.46 g, 91%) as a white powder. Mp = 290–293 ◦C
1
(decomposition); H NMR (400 MHz, DMSO-d6), d: 0.87 (9H,
t, 3J = 7 Hz, CH2CH3), 1.27 (12H, m, CH2), 1.59 (6H, m, CH2),
Tris(2-pentoxy-3-methyl-5-diethoxyphosphorylcarbamoylphenyl)-
methane (3c). Diethoxyphosphinyl isocyanate (0.46 g,
2.54 mmol) was added to the solution of tris(2-pentoxy-3-
methyl-5-aminophenyl)methane (0.25 g, 0.42 mmol) in methylene
chloride (10 mL). The reaction mixture was diluted with methanol
(10 mL) after stirring for 12 h. The solvents were removed at
room temperature under reduced pressure and the residue was
crystallized from methanol (5 mL) at −14 ◦C. The mother
solution was removed by syringe, diethyl ester (15 mL) was added
to the crystals, them were filtered off, washed with diethyl ester
and dried on the air to give compound 3c (0.265 g, 55%) as a
white powder. Mp = 211–213 ◦C (decomposition); 1H NMR
(400 MHz, DMSO-d6), d: 0.86 (9H, t, 3J = 7 Hz, CH2CH3), 1.24
(30H, m, CH2 and POCH2CH3), 1.56 (6H, m, CH2), 2.18 (9H, s,
ArCH3), 3.37 (6H, br s, ArOCH2), 4.03 (6H, m, POCH2), 6.39
(3H, d, 4J = 2.6 Hz, ArH), 6.43 (1H, s, Ar3CH), 7.43 (3H, d, 4J =
2.20 (9H, s, ArCH3), 2.21 (9H, s, ArCH3), 3.41 (6H, br s, OCH2),
4
6.41 (3H, d, J = 2.3 Hz, ArH), 6.45 (1H, s, Ar3CH), 7.04 (6H,
3
3
d, J = 8.2 Hz, ArHTol ), 7.26 (6H, d, J = 8.2 Hz, ArHTol ), 7.58
4
(3H, d, J = 2.3 Hz, ArH), 8.26 (3H, s, NH), 8.41 (3H, s, NH);
13C{ H} NMR (100.6 MHz, DMSO-d6), d: 13.8 (CH2CH3), 16.4
1
(ArCH3), 20.2 (ArCH3), 22.1 (CH2), 27.6 (CH2), 29.3 (CH2),
37.2 (Ar3CH), 71.9 (OCH2), 117.2 (CHAr), 118.0 (CHTol ), 118.9
(CHAr), 129.0 (CHTol ), 130.4 (CAr), 130.7 (CAr), 134.6 (CAr), 137.0
(CAr), 137.3 (CAr), 149.9 (CAr), 152.3 (C(O)); m/z (ESI) 1011.6
(100%) [M + Na]+, calc. 1012.31.
Dimer 3a·3a. 1H NMR (400 MHz, CDCl3), d: 0.82 (9H, t,
3J = 7 Hz, CH2CH3), 0.9–1.2 (12H, m, CH2), 1.35 (6H, m, CH2),
1.77 (9H, s, ArCH3), 2.18 (9H, s, ArCH3), 2.29 (3H, m, OCH2),
2.46 (3H, m, OCH2), 6.53 (3H, d, 4J = 2.4 Hz, ArH), 6.63 (1H, s,
Ar3CH), 6.86 (12H, s, ArHTol ), 7.09 (3H, s, NH), 7.14 (3H, d,
1
2
4J = 2.4 Hz, ArH), 8.29 (3H, s, NH); 13C{ H} NMR (100.6 MHz,
2.6 Hz, ArH), 7.84 (3H, d, JPH = 8.6 Hz, PNH), 8.63 (3H, s,
1
CDCl3), d: 14.1 (CH2CH3), 16.7 (ArCH3), 20.6 (ArCH3), 22.5
(CH2), 28.0 (CH2), 29.4 (CH2), 35.5 (Ar3CH), 71.8 (OCH2), 120.8
(CHTol ), 122.8 (CHAr), 126.2 (CHAr), 129.2 (CHTol ), 131.6 (CAr),
132.3 (CAr), 132.5 (CAr), 135.5 (CAr), 137.6 (CAr), 152.9 (CAr), 156.4
(C(O)).
ArNH); 13C{ H} NMR (100.6 MHz, DMSO-d6), d: 13.8 (s,
CH2CH3), 15.9 (d, 3JPC = 6.8 Hz, POCH2CH3), 16.3 (s, ArCH3),
22.0 (s, CH2), 27.6 (s, CH2), 29.3 (s, CH2), 37.1 (s, Ar3CH), 62.8
(d, 2JPC = 5.4 Hz, POCH2CH3), 71.9 (s, OCH2), 117.6 (s, CHAr),
119.3 (s, CHAr), 131.0 (s, CAr), 133.6 (s, CAr), 137.2 (s, CAr), 150.5
1
(s, CAr), 151.3 (d, 2JPC = 2.7 Hz, C(O)); 31P{ H} NMR (162 MHz,
Tris(2-pentoxy-3-methyl-5-p-tolylsulfonylureidophenyl)methane
(3b). Tosyl isocyanate (0.6 g, 3.05 mmol) was added to the
solution of tris(2-pentoxy-3-methyl-5-aminophenyl)methane
(0.3 g, 0.51 mmol) in methylene chloride (10 mL). The reaction
mixture was diluted with methanol (30 mL) after stirring for 12 h.
The solvents were removed at room temperature under reduced
pressure and the residue was treated with hexane (20 mL). After
removing hexane the rest was treated with methanol (10 ml) and
formed precipitate was filtered off, washed with methanol and
dried on the air to give compound 3b (0.42 g, 70%) as a white
powder. Mp = 243–246 ◦C (decomposition); 1H NMR (400 MHz,
DMSO-d6), d: 0.81 (9H, t, 3J = 7 Hz, CH2CH3), 1.20 (12H,
m, CH2), 1.50 (6H, m, CH2), 2.11 (9H, s, ArCH3), 2.38 (9H, s,
ArCH3), 3.29 (6H, br s, OCH2), 6.30 (3H, d, 4J = 2.4 Hz, ArH),
DMSO-d6), d: −0.51 (s). Only broad signals were observed in the
1H spectrum in CDCl3 and CD2Cl2. m/z (ESI) 1127.6 (4%) [M]+,
1149.5 (100%) [M + Na]+, calc. 1127.21.
Tris(2-pentoxy-3-methyl-5-(3,5-dichlorophenyl)ureidophenyl)-
methane (3d). was synthesized as described for 3a, yield is 85%,
white powder. Mp = 293–295 ◦C (decomposition); 1H NMR
(400 MHz, DMSO-d6), d: 0.86 (9H, t, 3J = 7 Hz, CH2CH3), 1.26
(12H, m, CH2), 1.58 (6H, m, CH2), 2.20 (9H, s, ArCH3), 3.40
(6H, br s, OCH2), 6.46 (1H, s, Ar3CH), 6.47 (3H, d, 4J = 2.4 Hz,
4
ArH), 7.11 (3H, m, ArClH), 7.46 (6H, d, J = 1.6 Hz, ArClH),
4
7.54 (3H, d, J = 2.4 Hz, ArH), 8.68 (3H, s, NH), 8.73 (3H, s,
1
NH); 13C{ H} NMR (100.6 MHz, DMSO-d6), d: 13.8 (CH2CH3),
16.3 (ArCH3), 22.1 (CH2), 27.6 (CH2), 29.3 (CH2), 37.2 (Ar3CH),
71.9 (OCH2), 116.0 (CHAr), 117.8 (CHAr), 119.4 (CHAr), 120.6
(CHAr), 130.9 (CAr), 133.9 (CAr), 134.0 (CAr), 137.3 (CAr), 142.1
(CAr), 150.3 (CAr), 151.9 (C(O)); m/z (ESI) 1153.6 (24%) [M]+,
1175.5 (100) [M + Na]+, 2308.1 (6) [2M]+, calc. 1153.91.
4
6.34 (1H, s, Ar3CH), 7.33 (3H, d, J = 2.4 Hz, ArH), 7.39 (6H,
3
3
d, J = 8 Hz, ArHTos ), 7.81 (6H, d, J = 8 Hz, ArHTos ), 8.66
(3H, s, NH), 10.21 (3H, br s, NH); 13C{ H} NMR (100.6 MHz,
1
DMSO-d6), d: 13.8 (CH2CH3), 16.2 (ArCH3), 20.9 (ArCH3), 22.0
(CH2), 27.5 (CH2), 29.2 (CH2), 37.0 (Ar3CH), 71.8 (OCH2), 117.9
(CHAr), 119.5 (CHAr), 127.4 (CHTos ), 129.3 (CHTos ), 130.9 (CAr),
132.9 (CAr), 136.9 (CAr), 137.1 (CAr), 143.7 (CAr), 148.8 (CAr),
150.7 (C(O)); m/z (ESI) 1203.7 (100%) [M + Na]+, 2385.4 (82)
[2M + Na]+, calc. 1204.50.
Dimer 3d·3d. 1H NMR (400 MHz, CDCl3), d: 0.84 (9H, t,
3J = 7 Hz, CH2CH3), 0.95–1.25 (12H, m, CH2), 1.42 (6H, m,
CH2), 1.94 (9H, s, ArCH3), 2.38 (3H, m, OCH2), 2.61 (3H, m,
4
OCH2), 6.51 (3H, d, J = 2.3 Hz, ArH), 6.72 (1H, s, Ar3CH),
6.92 (3H, m, ArClH), 6.96 (6H, d, 4J = 2 Hz, ArClH), 7.06 (3H, s,
Dimer 3b·3b. 1H NMR (400 MHz, CDCl3), d: 0.84 (9H, t,
3J = 7 Hz, CH2CH3), 1.27 (12H, m, CH2), 1.59 (6H, m, CH2),
2.24 (9H, s, ArCH3), 2.36 (9H, s, ArCH3), 3.14 (3H, d × t, 2J =
9 Hz, 3J = 6.7 Hz, OCH2), 3.80 (3H, d × t, 2J = 9 Hz, 3J = 6.7 Hz,
NH), 7.15 (3H, d, 4J = 2.3 Hz, ArH), 8.28 (3H, s, NH); 13C{ H}
1
NMR (100.6 MHz, CDCl3), d: 14.1 (CH2CH3), 16.8 (ArCH3), 22.6
(CH2), 27.9 (CH2), 29.5 (CH2), 35.2 (Ar3CH), 72.2 (OCH2), 118.1
(CHAr), 122.6 (CHAr), 123.1 (CHAr), 126.3 (CHAr), 130.8 (CAr),
3942 | Org. Biomol. Chem., 2006, 4, 3938–3944
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133.2 (CAr), 135.1 (CAr), 137.7 (CAr), 139.9 (CAr), 153.7 (CAr), 155.6
(C(O)).
3b. The position of the solvent molecule (chloroform) in crystals
of 3a and 3b is highly disordered.
Crystal data for 3a. C61H76N6O6*1/2CHCl3, M = 1097.92,
Tris(2-pentoxy-3-methyl-5-(3,5-dihex-5-enyloxyphenyl)ureido-
phenyl)methane (3e). A solution of 3,5-di(hex-5-enyloxy)benzoic
acid (1.34 g, 4.21 mmol), DPPA (1.18 g, 0.93 ml, 4.28 mmol) and
Et3N (0.43 g, 0.6 ml, 4.28 mmol) in toluene (90 mL) was stirred at
70 ◦C for 6 h under nitrogen atmosphere. After that tris(2-pentoxy-
3-methyl-5-aminophenyl)methane (0.41 g, 0.70 mmol) was added
to the solution and stirring was continued during 11 h at the
same conditions. Then the solvent was removed under reduced
pressure, hexane (100 mL) was added to the residue (oil) and it was
left in an ultrasonic bath for 15 min. Then hexane was decanted
and the crude product was crystallized from Et2O–methanol to
give 3e (0.87 g, 81%) as a white powder. Mp = 246–248 ◦C
(decomposition); 1H NMR (400 MHz, DMSO-d6), d: 0.87 (9H, t,
3J = 7 Hz, CH2CH3), 1.28 (12H, m, CH2), 1.46 (12H, m, CH2),
˚
˚
˚
monoclinic, a = 34.004(4) A, b = 15.738(3) A, c = 26.894(4) A,
◦
3
˚
b = 122.233(5) , V = 12175(3) A , T = 193 K, space group C2/c
(no. 15), Z = 8, l(Cu Ka) = 1.170 mm−1, 11539 reflections mea-
sured, 11539 reflections unique which were used in all calculations.
Crystal data for 3b. C61H76N6O12S3*2CHCl3, M = 1420.23,
˚
˚
˚
triclinic, a = 14.3620(6) A, b = 14.7300(6) A, c = 18.9930(6) A,
a = 67.8510(10)◦, b = 70.2640(10)◦, c = 80.3860(10)◦, V =
3
˚
3499.3(2) A , T = 120 K, space group P-1 (No.2), Z = 2, l(Mo
Ka) = 0.397 mm−1, 62249 reflections measured, 11692 reflections
unique (Rint = 0.1462) which were used in all calculations.
Molecular dynamics simulations
Computational methods. All molecular dynamics simulations
were performed using the AMBER 7 software package and the gaff
parameter set.18 The initial geometry of all models was obtained by
manual construction. Charges were derived following the standard
RESP procedure from a 6–31G* electrostatic potential calculated
with the GAMESS program and the assemblies were transferred
into the LEaP format.19,20 Subsequently, a rectangular box of
3
3
1.63 (18H, m, CH2), 2.05 (12H, d × t, J = 7 Hz, J = 7 Hz,
=
CH2CH CH2), 2.20 (9H, s, ArCH3), 3.41 (6H, br s, OCH2), 3.87
3
=
(12H, t, J = 6.6 Hz, OCH2), 4.97 (12H, m, CH CH2), 5.80
4
=
(6H, m, CH CH2), 6.07 (3H, br s, p-ArORH), 6.42 (3H, d, J =
4
2 Hz, ArH), 6.45 (1H, s, Ar3CH), 6.57 (6H, d, J = 1.8 Hz, o-
4
ArORH), 7.56 (3H, d, J = 2 Hz, ArH), 8.32 (3H, s, NH), 8.44
(3H, s, NH); 13C{ H} NMR (100.6 MHz, DMSO-d6), d: 13.8
1
˚
chloroform molecules (approximately 14 A solvent layer thickness
(CH2CH3), 16.3 (ArCH3), 22.1 (CH2), 24.6 (CH2), 27.6 (CH2),
28.0 (CH2), 29.3 (CH2), 32.7 (CH2), 37.2 (Ar3CH), 67.0 (OCH2),
on each side) was added. The solvated structures were subjected
to 5000 steps of minimization followed by a 30 ps belly dynamics
(300 K, 1 bar, 1 fs timestep) for solvent relaxation and by a
100 ps equilibration period. Subsequently, MD simulations were
performed in a NTP (300 K, 1 bar) ensemble for 9 ns using a
1 fs time step. Constant temperature and pressure conditions were
achieved by the weak coupling algorithm and isotropic position
scaling. Temperature and pressure coupling times of 0.5 and
1.0 ps, respectively, and the experimental compressibility value
of 100 × 10−6 bar−1 for chloroform were used. Bonds containing
hydrogen atoms were constrained to their equilibrium length using
the SHAKE algorithm. Snapshots were recorded every 2 ps. The
free monomeric units were subjected to a MD simulation of 3 ns
using the conditions as described above. For analysis purposes the
trajectories were averaged over 9 ns for 3a·3a, over the last 8 ns for
3b·3b and over the last 6.4 ns for 3a·3b.
=
71.9 (OCH2), 94.5 (CHAr), 96.7 (CHAr), 114.7 (CH CH2), 117.4
(CHAr), 118.9 (CHAr), 130.8 (CAr), 134.4 (CAr), 137.2 (CAr), 138.4
=
(CH CH2), 141.2 (CAr), 149.9 (CAr), 152.1 (C(O)), 159.8 (CAr);
m/z (ESI) 1537.3 (87%) [M]+, 1559.3 (85) [M + Na]+, 3073.6 (35)
[2M]+, calc. 1536.12.
Dimer 3e·3e. 1H NMR (400 MHz, CDCl3), d: 0.85 (9H, t,
3J = 7 Hz, CH2CH3), 1.20 (12H, m, CH2), 1.43 (18H, m, CH2),
1.62 (12H, m, CH2), 1.73 (9H, s, ArCH3), 2.06 (12H, d × t,
3
3
=
J = 7 Hz, J = 7 Hz, CH2CH CH2), 2.49 (3H, m, OCH2),
2.66 (3H, m, OCH2), 3.42 (6H, m, OCH2), 3.67 (6H, m, OCH2),
=
=
4.97 (12H, m, CH CH2), 5.78 (6H, m, CH CH2), 6.04 (3H, t,
4
4J = 2 Hz, p-ArORH), 6.10 (6H, d, J = 2 Hz, o-ArORH), 6.46
4
(3H, d, J = 2.5 Hz, ArH), 6.63 (1H, s, Ar3CH), 7.06 (3H, d,
4J = 2.5 Hz, ArH), 7.21 (3H, s, NH), 8.41 (3H, s, NH); 13C{ H}
1
NMR (100.6 MHz, CDCl3), d: 14.0 (CH2CH3), 16.5 (ArCH3),
22.7 (CH2), 25.4 (CH2), 28.0 (CH2), 28.6 (CH2), 29.7 (CH2), 33.5
(CH2), 35.6 (Ar3CH), 67.4 (OCH2), 72.0 (OCH2), 97.6 (CHAr),
Acknowledgements
We gratefully acknowledge financial support from the Deutsche
Forschungsgemeinschaft (Bo¨ 523/14, SFB 625, Th 520/5). We
thank Dr. V. Enkelmann (MPI for Polymer Research Mainz) for
collection of X-ray data of compound 3b.
=
99.7 (CHAr), 114.7 (CH CH2), 122.5 (CHAr), 126.0 (CHAr), 131.4
=
(CAr), 132.8 (CAr), 137.7 (CAr), 138.4 (CH CH2), 139.0 (CAr), 153.0
(CAr), 156.3 (C(O)), 160.2 (CAr).
Single-crystal X-ray diffraction
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˚
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The Royal Society of Chemistry 2006
©