How Selective Threading of Amides through Macrocylic Lactam Wheels Leads to Rotaxane Synthesis

Full text of DOI:10.1021/jo990042+

7236
J . Org. Chem. 1999, 64, 7236-7242
The mechanism of “threading the wheel” is assumed
How Selective Th r ea d in g of Am id es
to proceed via a pseudo- or semirotaxane complex. In
these complexes the guest is presumably fixed inside the
host cavity, orthogonal to the main plane of the macro-
cycle, by hydrogen bonds between the lactam amide
groups and either the acid chloride carbonyl or the amide
carbonyl of the pseudo- or semiaxle. Such preorganization
of the pseudo- or semiaxles would properly position their
reactive groups for further reaction with the stoppers.
th r ou gh Ma cr ocylic La cta m Wh eels Lea d s
to Rota xa n e Syn th esis
Christian Seel, Amir H. Parham, Oliver Safarowsky,
Gosia M. Hu¨bner, and Fritz Vo¨gtle*
Kekule´-Institut fu¨r Organische Chemie und Biochemie der
Universita¨t, D-53121 Bonn, Germany
Received J anuary 11, 1999
In tr od u ction
Chemistry has often drawn inspiration from molecules
with aesthetically appealing architecture. Mechanically
interlocked compounds such as rotaxanes, catenanes, and
knots are important examples and have grown in impor-
tance as a result of the development of template synthe-
ses that significantly improved their yields.1,2 In particu-
lar, rotaxanes are molecular compounds that consist of
one or more “wheels” with penetrating “axles”, which are
mechanically bound together and sterically prevented
from dethreading by bulky “stopper groups” at both ends
of the axle(s). Semirotaxanes and pseudorotaxanes are
analogous to conventional inclusion complexes in that
they are not restrained mechanically from dissociation
because the axles (in these cases semi- and pseudoaxles,
respectively) carry either one stopper only (semiaxle) or
no stopper at all (pseudoaxle).3 Rotaxanes, semirotax-
anes, and pseudorotaxanes are conveniently respresented
by formulas given as [axle@wheel], [semiaxle@wheel],
and [pseudoaxle@wheel], respectively. Semi- and pseu-
dorotaxanes that act as precursors in rotaxane syntheses
are called prerotaxanes. In recent years we have reported
the synthesis of a series of rotaxanes based on the
formation of amide bonds between a diacid chloride axle
part and two voluminous amino stoppers in the presence
of a macrocylic lactam (e.g., 1) as the wheel.1d
(1) For reviews, see: (a) Schill, G. Catenanes, Rotaxanes, and Knots;
Academic Press: New York, 1971. (b) Amabilino, D. B.; Stoddart, J . F.
Chem. Rev. 1995, 95, 2725-2825. (c) Gibson, H. W. In Large Ring
Molecules; Semlyen, J . A., Ed.; Wiley: Chichester, 1996; pp 191-262.
(d) J a¨ger, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930-
944. (e) Sauvage, J . P., Dietrich-Buchecker, C. O.; Eds. Molecular
Catenanes, Rotaxanes and Knots; VCH-Wiley: Weinheim, 1999.
(2) For recent accounts on rotaxanes and catenanes with different
types of template syntheses, see: (a) Adams, H.; Carver, F. J .; Hunter,
C. A. J . Chem. Soc., Chem. Commun. 1995, 809-810. (b) Born, M.;
Ritter, H. Adv. Mater. 1996, 8, 149-151. (c) Hamilton, D. G.; Sanders,
J . K. M.; Davies, J . E.; Clegg, W.; Teat, S. J . Chem. Commun. 1997,
897-898. (d) Harada, A.; Li, J .; Kamachi, M. Chem. Commun. 1997,
1413-1414. (e) Herrmann, W.; Schneider, M.; Wenz, G. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2511-2514. (f) Gong, C.; Gibson, H. W. Angew.
Chem., Int. Ed. 1998, 37, 310-314. (g) Kolchinski, A. G.; Alcock, N.
W.; Roesner, R. A.; Busch, D. H. Chem. Commun. 1998, 1437-1438.
(h) Fujita, M.; Aoyagi, M.; Ibukuro, F.; Ogura, K.; Yamaguchi, K. J .
Am. Chem. Soc. 1998, 120, 611-612. (i) Leigh, D. A.; Murphy, A.;
Smart, J . P.; Deleuze, M. S.; Zerbetto, F. J . Am. Chem. Soc. 1998, 120,
6458-6467. (j) Armaroli, N.; Diederich, F.; Dietrich-Buchecker, C. O.;
Flamigni, L.; Marconi, G.; Nierengarten, J .-F.; Sauvage, J .-P. Chem.
Eur. J . 1998, 4, 406-416. (k) Ashton, P. R.; Ballardini, R.; Balzani,
V.; Fyfe, M. C. T.; Gandolfi, M. T.; Mart´ınez-D´ıaz, M.-V.; Morosini,
M.; Schiavo, C.; Shibata, K.; Stoddart, J . F.; White, A. J . P.; Williams,
D. J . Chem. Eur. J . 1998, 4, 2332-2341. (l) Linke, M.; Chambron, J .-
C.; Heitz, V.; Sauvage, J .-P.; Semetey, V. Chem. Commun. 1998, 2469-
2470. (m) Hu¨bner, G. M.; Gla¨ser, J .; Seel, C.; Vo¨gtle, F. Angew. Chem.,
Int. Ed. 1999, 38, 383-386.
Resu lts a n d Discu ssion
Host/Gu est Stu d ies. A deeper and more detailed
insight into the mechanisms of template-assisted syn-
thesis involving macrocyclic lactams could lead to new
synthetic strategies. Therefore, we used NMR titrations
in CD2Cl2 to study the binding properties of the wheels
14 with a range of neutral organic molecules. Studies of
complexation of quinone and other cyclic dicarbonyl
compounds by such macrocycles has been reported ear-
lier.5
The NMR titration results show that tetralactam 1a 4a
is selective for secondary amides (e.g., 2, 3a -e, 4a , and
(4) (a) Vo¨gtle, F.; Ha¨ndel, M.; Meier, S.; Ottens-Hildebrandt, S.; Ott,
F.; Schmidt, T. Liebigs Ann. 1995, 739-743. (b) Ottens-Hildebrandt,
S.; Schmidt, T.; Harren, J .; Vo¨gtle, F. Liebigs Ann. 1995, 1855-1860.
(c) Braschohs, S.; Ph. D. thesis, University of Bonn, Germany, 1998.
(5) (a) Hunter, C. A. J . Chem. Soc., Chem. Commun. 1991, 749-
751. (b) Hunter, C. A.; Purvis, D. H. Angew. Chem., Int. Ed. Engl. 1992,
31, 792-794. (c) Hunter, C. A.; Shannon, R. J . Chem. Commun. 1996,
1361-1362. (d) Allott, C.; Adams, H.; Bernad, P. L., J r.; Hunter, C.
A., Rotger, C.; Thomas, J . A. Chem. Commun. 1998, 2449-2450.
(3) See also: Ashton, P. R.; Philp, D.; Spencer, N.; Stoddart, J . F. J .
Chem. Soc., Chem. Commun. 1991, 1677-1679.
10.1021/jo990042+ CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/21/1999

Notes
J . Org. Chem., Vol. 64, No. 19, 1999 7237
(a )
(b)
F igu r e 1. Molecular recognition of neutral organic molecules by wheel 1a in CD2Cl2. (a) Analogous secondary amide axle guests.
The association constants (M-1) are given in parentheses. (b) Derivatives that are not significantly bound.
5, see Figure 1a). The slight differences in the association
constants of these guests are probably caused by the
influence of substituents (aromatic versus aliphatic) on
the hydrogen bond donor and acceptor properties (pKa
of NH and pKb of CO) of the guest. The signals for guest
protons in the vicinity of the amide bond undergo
stronger complexation-induced shifts than ones further
away. This suggests a positioning of the guest that places
the amide linkage in the most intense positive region of
diamagnetic anisotropy for the arene units of the wheel,
while placing other positions along the guest in regions
of decreasing diamagnetic anisotropy that scales with the
distance from the amide linkage. Such a positioning is
consistent with an orthogonal orientation of the guests
inside the host cavity.
Carboxylic acid chlorides (3i) and diacid chlorides (4b)
are not significantly bound. This rules out the possibility
of pseudorotaxanes, such as [4b@1a ], being the key
intermediates in the synthesis; rather it strongly hints
at the formation of a reactive semirotaxane complex
analogous to that of the type [3d @1a ] as the crucial
intermediate in rotaxane generation.
formation, i.e., it does not hinder threading of the wheel
by the associate axle part of the semiaxle. However, the
axle 4c with two tetrabenzoylglucose stoppers6 shows no
affinity toward the tetralactam. This confirms that the
presence of two bulky stoppers such as with 4c prevent
the axle from “slipping” through the macrocycle to form
a rotaxane and suggests that as a result no favorable
contact between the amide groups of the two molecules
is possible.
Upon complexation, the amide proton signals for both
the wheel and the guests exhibit downfield shifts typical
of hydrogen bonding. X-ray structures of the wheels
usually show all four NH protons more or less directed
toward the center of the cavity, thus providing multiple
docking sites for proton acceptor groups of enclosed
solvent molecules.4c,5,7 In related catenanes, however, one
amide bond in each macrocycle is inverted with the
carbonyl group pointing inward so that it contacts (i.e.,
(6) Schmidt, T.; Schmieder, R.; Mu¨ller, W. M.; Kiupel, B.; Vo¨gtle,
F. Eur. J . Org. Chem. 1998, 2003-2007.
(7) (a) Ottens-Hildebrandt, S.; Meier, S.; Nieger, M.; Vo¨gtle, F.;
Weber, E. Supramol. Chem. 1995, 5, 133-138. (b) Vo¨gtle, F.; Du¨nn-
wald, T.; Schmidt, T. Acc. Chem. Res. 1996, 29, 451-460. (c) Fischer,
C.; Nieger, M.; Mogck, O.; Bo¨hmer, V.; Ungaro, R.; Vo¨gtle, F. Eur. J .
Org. Chem. 1998, 155-161. (d) See also: Clegg, W.; Gimenez-Saiz, C.;
Leigh, D. A.; Murphy, A.; Slawin, A. M. Z.; Teat, S. J . J . Am. Chem.
Soc. 1999, 121, 4124-4129.
Voluminous groups such as 4-tritylphenyl adjacent to
the amide bond as in semiaxles 3d and 3e do not
influence the binding strength. Hence, steric hindrance
from the presence of one stopper does not affect complex

7238 J . Org. Chem., Vol. 64, No. 19, 1999
Notes
H-bonds with) an NH proton of the other ring.2a,8,9
Furthermore, at room temperature there is a weak NOE
between the resonances of the lactam NH protons and
the isophthaloyl H-3 and H-5 protons, in addition to the
expected strong contact between the NH and the H-2
protons. This suggests that in solution there is an
equilibrium between the cisoid and transoid rotamers,
with the latter being disfavored. All of the lactam spectra
retain their general shape and appearance during the
titrations, suggesting that the symmetry of the cisoid
orientation is maintained. Rapid conformational ex-
change could, however, explain this. Low-temperature
experiments (down to -70 °C) gave no further evidence
of any conformational equilibria existing.
In the solid-state, lactams such as 1 can complex esters
such as ethyl acetate, as evidenced by several X-ray
structures. In these structures the ester carbonyl oxygen
and both amide protons of one isophthalic amide moiety
in the wheel form bifurcated hydrogen bonds.7 In solu-
tion, however, the binding of esters (3g and 4e), which
are weaker hydrogen bond acceptors than amides, is not
very pronounced. Likewise, in solution the affinity for
binding tertiary amides (3f and 4d ) is strongly dimin-
ished. Also, amines such as stopper 6a , alcohols (6b),
ethers (m-dimethoxybenzene), benzoic acids (3h ), ketones
(fluorenone, benzil), phenylisocyanate, and sulfonamides
(the analogue of 3a ) are only weakly or negligibly bound.
Monosulfonamide trilactam 1b, which has also been
used as the wheel in rotaxane syntheses,4b and the
dithiamide macrocycle 1c4c both bind secondary amide
pseudoaxles similarly as does the tetralactam 1a . How-
ever, only the isophthalic amide residues of these wheels
show the typical upfield shift of NH protons caused by
hydrogen bonding. In other words, the phenylsulfonyl and
dithiaamide moieties do not seem to act as a binding site
for the guests. This is consistent with the previously
noted observation that the sulfonamide analogue of 3a
is not bound by the tetralactam 1a .
fact, the nonplanar diamide 4a has such a limited
solubility in CD2Cl2 (ca. 8 mM) that the resulting
uncertainty renders the Ka measured by our NMR
titration technique merely an approximation. Compounds
4f and 4g dissolve even to a lesser extent and thus could
not be titrated under the experimental conditions em-
ployed.
It has to be pointed out that there is an uncertainty
about the hydrogen bonding pattern in the amide com-
plexes. The fact that tertiary amides (which lack an NH
proton) are not bound might indicate that in the binding
of secondary amides the guest NH proton is directly
involved. However, this would imply that one isophthal-
amide unit of the wheel has to adopt a transoid confor-
mation which is unfavored in the free macrocycle. Also,
as a result of steric reasons, only one hydrogen bond could
be formed instead of the bifurcated motif seen in X-ray
structures as mentioned above. However, NOE experi-
ments give no evidence for the transoid conformation of
the macrocycle. Also, the fact that in the rotaxanes
described below no downfield shifts of the axle NH
protons caused by hydrogen bonding have been observed
and this is consistent with the bifurcated motif.12
In summary, secondary amides are well bound by
macrocycles of appropriate size that feature at least one
isophthalic diamide group as the docking site. If the
guests carry functional groups for condensation reactions
with stopper units and are preorganized in the complexes
to give pseudorotaxanes, then synthesis of a great variety
of rotaxanes is feasable.1d
Rota xa n e Syn th eses. To test the hypothesis that the
crucial intermediate in our rotaxane synthesis is a
semirotaxane having the respective semiaxle fixed inside
the wheel by hydrogen bonds between the amide groups
of the two components, we designed the following experi-
ments as depicted in Scheme 1. The secondary amide 8a ,
which is similar to the guest 3d , and the analogous ester
8b were synthesized following standard procedures. Both
are potential axle precursors because they are stoppered
with a trityl group on one end and carry an anilinic NH2
group on the other; the NH2 group can react with a
second stopper containing a benzoyl chloride group (9).
Rotaxanes should be possible only if wheel 1a and the
semiaxles form appropriately preorganized inclusion
complexes. To stabilize the prerotaxane complexes [8@1a ]
we worked at low temperature (-5 °C) and as high a
concentration as possible (4 mM; about the limit of
solubility for 1a ). These conditions shift the association
equilibrium toward complexation. Indeed, rotaxane 10a
was formed as expected and with the high yield of 69%,
a result that strongly supports our mechanistic model.
In contrast, only 4% of the analogous ester rotaxane 10b
was obtained; this is consistent with a weak but obviously
not negligible complexation of esters by 1a in solution.
It was possible to synthesize several rotaxanes with
aliphatic axle middle parts by this synthetic approach.
Therefore any contribution from hydrophobic arene-
arene interactions to the mechanism of preorganiztion
cannot be very pronounced. In particular, aliphatic diacid
chlorides were reacted with 2 equiv of stopper 6a in the
presence of wheel 1a . The yields for the rotaxanes 11-
Furthermore, open-chain isophthalic diamide 4f,9 which
also serves as a precursor in the macrocycle synthesis,
and the open-chain tetraamide 4g do not reveal any
significant affinity for amide 3c. Obviously a macrocyclic
structure of the host is essential for binding. The reason
might be that open-chain isophthalic diamides have a
trans conformation of the two amide groups rather than
the cis conformation as in the macrocycles, i.e., the NH
protons point in opposite directions, which would be
unfavorable for the bifurcated hydrogen bonding of a
carbonyl oxygen.10 Because the structurally similar dia-
mide 4a is relatively well bound as a guest by macrocycle
1a as a host, it can be assumed that similar pseudoro-
taxane complexes such as [4f@1a ] serve as templates for
the related catenane synthesis. Because diamides tend
to be poorly soluble,11 especially in nonpolar solvents such
as chloroform or dichloromethane, their association
constants could not be determined by NMR titration. In
(8) (a) Ottens-Hildebrandt, S.; Nieger, M.; Rissanen, K.; Rouvinen,
J .; Meier, S.; Harder, G.; Vo¨gtle, F. J . Chem. Soc., Chem. Commun.
1995, 777-778. (b) A rotaxane was reported where one amide bond
also seems to be inverted: Leigh, D. A.; Murphy, A.; Smart, J . P.;
Slawin, A. M. Z. Angew. Chem., Int. Ed. Engl. 1997, 36, 752-756.
(9) Hunter, C. A. J . Am. Chem. Soc. 1992, 114, 5303-5311.
(10) (a) Carver, F. J .; Hunter, C. A.; Shannon, R. J . J . Chem. Soc.,
Chem. Commun. 1994, 1277-1280. See also ref 5b and: Adams, H.;
Harris, K. D. M.; Hembury, G. A.; Hunter, C. A.; Livingstone, D.;
McCabe, J . F. Chem. Commun. 1996, 2531-2532.
(12) After submission of this paper we were able to determine the
X-ray structure of a related rotaxane. It indeed shows the bifurcated
hydrogen bonding pattern between the NH protons of one isophthal-
amide group of wheel 1b and an amide oxygen of the axle. Reuer, C.;
Nieger, M.; Vo¨gtle, F., unpublished results.
(11) See also: Eblinger, F.; Schneider, H.-J . Angew. Chem., Int. Ed.
1998, 37, 826-829.

Notes
J . Org. Chem., Vol. 64, No. 19, 1999 7239
Sch em e 1
13 from adamantane-1,3-dicarbonyl chloride, bicyclo-
[2.2.2]octane-1,4-dicarbonyl chloride, and succinyl chlo-
ride were 44%, 25%, and 23%, respectively. These yields
are lower than for the case of 10a most likely because
two bonds have to be formed instead of just one. Ad-
ditionally, the synthesis of rotaxane 14 from the N-
hydroxysuccinimide ester of sebacinic acid (instead of its
diacid chloride) gave a yield of 11%. This further indicates
that recognition and binding of the acid chloride group
is not crucial for rotaxane formation. It also demonstrates
that active esters are useful alternatives to acid chlorides
in the synthesis of rotaxanes with amide axles.
10a and 0.35 ppm for 10b. The amide proton signals of
the wheels, however, shift downfield, obviously as a result
of hydrogen bonding with the carbonyl oxygens of the
axles. The same is not true, however, for the amide
protons of the axles. This stands in contrast to the
downfield shifts of the NH protons of the guests in the
titrations, a fact that is not easy to explain. In 10a the
signals of the two pairs of lactam NH protons shift by
1.05 ppm on average. In 10b , which has a mono-
amide-monoester axle, the effect is only about half as
large at 0.58 ppm. Here only one isophthalamide unit at
a time can interact with the amide group of the axle.
Hydrogen bonding to the ester group seems much less
effective, which correlates with the weak binding of esters
as guests by the tetralactam host 1a .
Low solubility of the rotaxanes 11-14 with aliphatic
axle middle parts (and even lower solubility of the
corresponding free axles) prevented the use of pure CDCl3
as a solvent; mixtures with CD3OD or DMSO-d6 were
required. Because these media weaken or suppress the
formation of hydrogen bonds, the induced changes in the
chemical shifts of the wheel amide protons are far less
pronounced for these samples. Line-broadening of the
signals of the adamantane residue and overlap with
signals of the wheel in rotaxane 11 make it difficult to
assign and quantify the shifts. The signal of the ada-
mantane CH2 group not neighboring the carbonyls (CH2-
10) shifts 1.4 ppm and the axle NH signal 0.5 ppm upfield
in DMSO-d6. Similarly, in 12 the bicyclo[2.2.2]octane
signal shifts 0.8 ppm and the axle NH proton 0.4 ppm in
DMSO-d6/CDCl3 (2:1). In the case of rotaxanes 13 and
14, the shorter succinamide axle in 13 leads to somewhat
larger upfield shifts. The NH signals of the axle shift 1.3
ppm in 13, as compared to 0.4 ppm in 14; the signals
due to the methylene groups shift 0.75 ppm for 13, as
compared to 0.4-0.6 ppm for 14 in DMSO-d6/CDCl3
(1:1).
Ch em ical Sh ifts In du ced by th e Mech an ical Bon d-
in g in Rota xa n es. All of the newly synthesized rotax-
anes exhibit the typical interlocking-induced shifts of
signals in the NMR spectra. Signals of protons in the
central parts of the axles undergo the strongest upfield
shifts because they are positioned deeply inside the
negative region of the anisotropic fields of the aromatic
units of the cyclophane wheel. The aromatic protons of
the 4-aminobenzoyl unit shift by 1.9 and 1.8 ppm upfield
in case of rotaxane 10a and 1.5 and 1.3 ppm in case of
10b. The further the protons are away from the center
of the complex, the less pronounced are the effects. For
example, the ∆δ values for the H-2 and H-6 protons of
the 3,5-di-tert-butylbenzoyl stopper are only 0.3 ppm for
Con clu sion s
We recently published a study of the anion-binding
abilities of macrocyclic tetralactams.2m We now report
that in binding neutral molecules in nonpolar solvents

7240 J . Org. Chem., Vol. 64, No. 19, 1999
Notes
J ) 8.6 Hz), 8.13 (2H, d, J ) 8.6 Hz). 13C NMR (62.9 MHz,
CDCl3) δ 64.59 (Cq), 67.39 (CH2), 117.63 (CH), 120.53 (CH),
124.08 (Cq), 125.98 (CH), 127.52 (CH), 128.39 (CH), 128.53 (CH),
128.66 (CH), 131.08 (CH), 131.55 (CH), 132.13 (CH), 135.57 (Cq),
142.69 (Cq), 144.30 (Cq), 146.57 (Cq), 148.84 (Cq), 152.78 (Cq),
166.64 (Cq). FABMS (3-nitrobenzyl alcohol): 590.3 (M + H)+.
Anal. Calcd for C40H31NO4: C, 81.47; H, 5.30; N, 2.38. Found: C,
81.30; H, 5.25; N, 2.32.
Syn th esis of Sem ia xles 8a a n d 8b. A 0.6 mmol portion of
Z-8a or Z-8b and 10 mg of Pd/C in 40 mL of ethanol are shaken
under 3 bar H2 atmosphere for 4 h. After filtration the solvent
is evaporated, and the residue is purified by column chroma-
tography [SiO2, CH2Cl2].
(4-Am in oben z)-p-tr ityla n ilid e (8a ). Colorless solid. Yield:
265 mg (91%). Mp: 232 °C. Rf 0.11 (CH2Cl2). 1H NMR (250 MHz,
CDCl3) δ 4.07 (2H, s, NH2), 6.69 (2H, d, J ) 8.6 Hz), 7.20 (2H,
d, J ) 8.6 Hz), 7.15-7.30 (15H, m), 7.48 (2H, d, J ) 8.6 Hz),
7.65 (1H, s, NH), 7.68 (2H, d, J ) 8.6 Hz). 13C NMR (62.9 MHz,
CDCl3/CD3OD 5:1) δ 64.37 (Cq), 113.91 (CH), 119.18 (CH), 125.69
(CH), 128.85 (CH), 130.86 (CH), 131.37 (CH), 136.01 (Cq), 136.09
(Cq), 142.36 (Cq), 146.59 (Cq), 150.18 (Cq), 166.41 (CO). FABMS
(3-nitrobenzyl alcohol): 455.3 (M + H)+. Anal. Calcd for
C32H26N2O‚0.5H2O: C, 83.09; H, 6.05 N, 5.67. Found: C, 83.39;
H, 5.73 N, 5.91.
these host molecules are rather selective for secondary
amides. Both types of molecular recognition (i.e., of
anions and of secondary amides) have been successfully
utilized for the template-assisted synthesis of mechani-
cally interlocked molecules. We are currently investigat-
ing different linking reaction types as new strategies for
synthesizing these intriguing compounds and possibly
extending them to more sophisticated structures.
Exp er im en ta l Section
Ma ter ia ls. 4-Tritylaniline (Aldrich), 4-tritylphenol (Lan-
caster), 3,5-di-tert-butylbenzoic acid (Lancaster), 4-aminobenzoic
acid (Merck), adamantane-1,3-dicarboxylic acid (Fluka), succinyl
dichloride (Merck), sebacoyl dichloride (Merck), and all other
chemicals were of the best commercial quality available and used
as received. The macrocycles4 and bicyclo[2.2.2]octane-1,4-di-
carboxylic acid13 were prepared as previously reported. Acid
chlorides and guest compounds, if not commercial, were syn-
thesized and purified by standard procedures.
Micr oa n a lyses were performed by the analytical facility of
the Kekule´-Institut fu¨r Organische Chemie und Biochemie of
the University of Bonn. Solvent retention in the analytical
samples was verified by NMR. One equivalent of ethyl acetate
is routinely found after column chromatography of samples of
tetralactam wheels and rotaxanes of this type.7
Assign m en ts of the signals of NH protons in the 1H NMR
spectra were made by deuterium exchange experiments and the
pronounced solvent dependency of the chemical shifts.
Deter m in a tion of Bin d in g Con sta n ts. Titrations were
performed by adding aliquots (usually 25, 30, 35, 40, 50, 70, 100,
and 150 µL) of a solution of the guest to a solution (500 µL) of
the macrocycle, both in CD2Cl2. Typical concentrations were 30
mM of guest and 4 mM of host, but higher concentrations were
used in cases of weak binding. The complexation of the guests
was monitored by measuring the complexation-induced shifts
of the signals for the NH protons, the H-2 protons of the
isophthalic acid residues, and the arylic methyl protons of the
macrocycles. Standard nonlinear curve fitting of the shift values
gave the association constants (Ka), the average of which is given
in each case.14 The experimental data, including J ob-plots,15 were
consistent with 1:1 stoichiometry for all complexes.
Z-P r otected Sem ia xles Z-8a a n d Z-8b. A solution of 360
mg (1.13 mmol) of N-benzyloxycarbonyl-4-aminobenzoyl chlo-
ride16 in 50 mL of CH2Cl2 is added dropwise during 2 h to a
solution of 8 drops of triethylamine and 379 mg (1.13 mmol) of
4-tritylaniline (6a ) or 380 mg (1.13 mmol) of 4-tritylphenol (6b)
in 50 mL of CH2Cl2. After 2 h of additional stirring the solvent
is evaporated, and the residue is purified by column chroma-
tography [SiO2, CH2Cl2].
(4-Ben zyloxyca r bon yla m in oben z)-4-tr ityla n ilid e (Z-8a ).
Colorless solid. Yield: 520 mg (79%). Mp: 96 °C. Rf 0.14 (CH2-
Cl2). 1H NMR (250 MHz, CDCl3) δ 5.21 (2H, s), 6.91 (1H, s, NH),
7.15-7.40 (22H, m), 7.49 (2H, d, J ) 8.6 Hz), 7.50 (2H, d, J )
8.6 Hz), 7.75 (1H, s, NH), 7.79 (2H, d, J ) 8.6 Hz). 13C NMR
(62.9 MHz, CDCl3/CD3OD 5:1) δ 64.38 (Cq), 66.78 (CH2), 117.82
(CH), 119.31 (CH), 125.69 (CH), 127.25 (CH), 127.87 (CH),
128.09 (CH), 128.18 (CH), 128.35 (CH), 128.87 (Cq), 130.86 (CH),
131.39 (CH), 135.80 (Cq), 138.88 (Cq), 141.57 (Cq), 142.66 (Cq),
146.56 (Cq), 153.65 (Cq), 166.21 (Cq). FABMS (3-nitrobenzyl
alcohol): 589.2 (M + H)+. Anal. Calcd for C40H32N2O3‚0.5H2O:
C, 80.38; H, 5.56; N, 4.67. Found: C, 80.57; H, 5.42; N, 4.55.
4-Tr itylph en yl 4-(Ben zyloxycar bon ylam in o)ben zoate (Z-
8b). Colorless solid. Yield: 379 mg (58%). Mp: 200 °C. Rf 0.66
(CH2Cl2). 1H NMR (250 MHz, CDCl3) δ 5.24 (2H, s), 7.01 (1H, s,
NH), 7.10 (2H, d, J ) 8.6 Hz), 7.15-7.40 (22H, m), 7.52 (2H, d,
p-Tr itylp h en yl 4-Am in oben zoa te (8b). Colorless solid.
Yield: 256 mg (88%). Mp: 245 °C. Rf 0.41 (CH2Cl2). 1H NMR (250
3
MHz, CDCl3) δ 4.1 (2H, br, NH), 6.67 and 7.98 (4H, AA′BB′, J
) 8.5 Hz), 7.08 (2H, half of AA′BB′, 3J ) 8.7 Hz), 7.15-7.25 (17H,
m). 13C NMR (62.9 MHz, CDCl3) δ 64.57 (Cq), 114.12 (CH), 120.66
(CH), 125.95 (CH), 127.50 (CH), 127.57 (Cq), 131.09 (CH), 132.06
(CH), 132.28 (CH), 143.99 (Cq), 146.60 (Cq), 146.63 (Cq), 149.05
(Cq), 165.01 (CO). FABMS (3-nitrobenzyl alcohol): 456.2 (M +
H)+. Anal. Calcd for C32H25NO2: C, 84.37; H, 5.53 N, 3.07. Found:
C, 84.36; H, 5.65 N, 2.93.
Syn th esis of Rota xa n es 10a a n d 10b. A 384 mg (0.4 mmol)
portion of tetralactam 1a , 0.4 mmol of semiaxle 8a or 8b, and
12 drops of triethylamine are dissolved in 100 mL of CH2Cl2 and
cooled to -5 °C. A solution of 102 mg (0.4 mmol) of 3,5-di-tert-
butylbenzoyl chloride 9 in 100 mL of CH2Cl2 is added dropwise
during 4 h. After 2 h of additional stirring the solvent is
evaporated, and the residue is purified by column chromatog-
raphy [SiO2, CH2Cl2/ethyl acetate (25:1)] to yield the rotaxanes
and free axles. 10a . Colorless solid. Yield: 449 mg (69%). Mp:
>320 °C. Rf 0.43 (CH2Cl2/ethyl acetate 25:1). 1H NMR (250 MHz,
CDCl3/CD3OD 5:1) δ 1.23 (18H, s), 1.41 (9H, s), 1.50 (4H, br),
1.61 (8H, br), 1.84 (12H, s), 1.85 (12H, s), 2.22 (4H, br), 2.28
3
(4H, br), 6.01 and 6.12 (4H, AA′BB′, J ) 8.4 Hz), 6.95 (4H, s),
6.96 (4H, s), 7.15-7.35 (20H, m), 7.49 (2H, d, J ) 1.6 Hz), 7.59
(1H, t, J ) 1.6 Hz), 7.67 (1H, t, J ) 7.8 Hz), 8.11 (2H, d, J ) 7.8
Hz), 8.17 (2H, s), 8.25 (1H, s), 8.40 (1H, s), 8.51 (2H, s, NH),
8.55 (2H, s, NH). 13C NMR (62.9 MHz, CDCl3) δ 18.53 (CH3),
18.59 (CH3), 22.86 (CH2), 22.99 (CH2), 26.26 (CH2), 31.24 (CH3),
34.96 (Cq), 35.22 (Cq), 35.64 (CH2), 36.58 (CH2), 45.32 (Cq), 64.63
(Cq), 118.45 (CH), 121.62 (CH), 124.08 (CH), 124.22 (CH), 125.88
(CH), 126.13 (CH), 126.44 (CH), 126.70 (CH), 126.90 (CH),
127.22 (CH), 127.44 (CH), 127.65 (CH), 128.57 (CH), 129.73
(CH), 130.97 (CH), 131.34 (Cq), 131.46 (CH), 131.62 (Cq), 131.75
(Cq), 131.89 (Cq), 132.18 (CH), 134.46 (Cq), 134.70 (Cq), 134.77
(Cq), 135.07 (Cq), 135.16 (Cq), 139.57 (Cq), 144.46 (Cq), 146.37
(Cq), 148.37 (Cq), 148.51 (Cq), 151.85 (Cq), 153.43 (Cq), 165.95
(CO), 166.59 (CO), 167.16 (CO), 169.17 (CO). MALDI-TOFMS
(2,5-dihydroxybenzoic acid): 1654.7 (M + Na)+, 1671.7 (M + K)+.
Anal. Calcd for C111H118N6O6‚2H2O‚C4H8O2: C, 78.65; H, 7.46;
N, 4.79. Found: C, 78.86; H, 7.50; N, 4.81.
4-(3,5-Di-ter t-bu tylben zam ido)ben z-(4-tr itylan ilide) (fr ee
a xle of 10a ). Colorless solid. Yield: 40 mg (15%). Mp: 198 °C.
1
Rf 0.31 (CH2Cl2/ethyl acetate 25:1). H NMR (250 MHz, CDCl3)
3
δ 1.36 (9H, s), 7.15-7.30 (19H, m), 7.52 (2H, half of AA′BB′, J
) 8.8 Hz), 7.63 (1H, t, J ) 1.7 Hz), 7.66 (2H, d, J ) 1.7 Hz),
(13) (a) Roberts, J . D.; Moreland, W. T.; Frazer, W. J . Am. Chem.
Soc. 1953, 75, 637-641. (b) Nuding, G.; Vo¨gtle, F.; Danielmeier, K.;
Steckhan, E. Synthesis 1996, 1, 71-76.
3
7.78 (1H, s, NH), 7.78 and 7.85 (4H, AA′BB′, J ) 8.7 Hz), 7.90
(1H, s, NH).13C NMR (62.9 MHz, CDCl3) δ 31.09 (CH3), 34.82
(Cq), 64.42 (Cq), 119.29 (CH), 120.17 (CH), 121.44 (CH), 125.72
(CH), 126.14 (CH), 127.29 (CH), 128.07 (CH), 130.24 (Cq), 130.90
(CH), 131.44 (CH), 133.85 (Cq), 135.95 (Cq), 141.36 (Cq), 142.69
(Cq), 146.59 (Cq), 151.24 (Cq), 166.31 (CO), 167.99 (CO). MALDI-
TOFMS (2,5-dihydroxybenzoic acid): 671.9 (M + H)+, 693.9 (M
(14) See: Wilcox, C. S. In Frontiers in Supramolecular Organic
Chemistry and Photochemistry; Schneider, H.-J ., Du¨rr H., Eds.; VCH:
Weinheim, 1991; pp 123-143 and references therein.
(15) Blanda, M. T.; Horner, J . H.; Newcomb, M. J . Org. Chem. 1989,
54, 4626-4636.
(16) Ruggli, P.; Dahn, H. Helv. Chim. Acta 1944, 27, 1116-1122.

Notes
J . Org. Chem., Vol. 64, No. 19, 1999 7241
+ Na)+, 709.8 (M + K)+. Anal. Calcd for C47H46N2O2‚2H2O: C,
79.86; H, 7.13; N, 3.96. Found: C, 80.29; H, 6.87; N, 3.91.
10b. Colorless solid. Yield: 24 mg (3.6%). Mp: 285 °C. Rf 0.31
(CH2Cl2/ethyl acetate 25:1). 1H NMR (250 MHz, CDCl3) δ 1.23
(18H, s), 1.38 (9H, s), 1.50 (4H, br), 1.60 (8H, br), 1.88 (24H, s),
2.24 (8H, br), 6.31 (2H, d, J ) 8.3 Hz), 6.77 (2H, d, J ) 8.6 Hz),
6.85-6.95 (12H, m), 7.15-7.30 (17H, m), 7.45 (2H, s), 7.61 (1H,
s), 7.61 (1H, t, J ) 7.7 Hz), 7.73 (4H, s, NH), 8.02 (1H, s), 8.12
(2H, d, J ) 7.7 Hz), 8.18 (3H, s). 13C NMR (62.9 MHz, CDCl3) δ
18.56 (CH3), 18.59 (CH3), 22.96 (CH2), 26.28 (CH2), 31.22 (CH3),
31.33 (CH3), 34.94 (Cq), 35.27 (Cq), 35.65 (CH2), 36.21 (CH2),
45.35 (Cq), 64.56 (Cq), 119.50 (CH), 121.16 (CH), 122.54 (CH),
122.97 (CH), 125.64 (CH), 125.83 (Cq), 125.98 (CH), 126.19 (CH),
126.76 (CH), 126.85 (CH), 127.24 (CH), 127.52 (CH), 127.65
(CH), 128.76 (CH), 129.80 (CH), 130.95 (CH), 131.07 (CH),
131.19 (Cq), 131.27 (Cq), 131.52 (CH), 131.85 (Cq), 132.18 (CH),
134.55 (Cq), 134.83 (Cq), 134.94 (Cq), 141.69 (Cq), 145.05 (Cq),
146.32 (Cq), 146.56 (Cq), 148.20 (Cq), 148.45 (Cq), 151.87 (Cq),
153.76 (Cq), 165.58 (CO), 166.08 (CO), 166.69 (CO), 168.30 (CO).
MALDI-TOFMS (2,5-dihydroxybenzoic acid): 1654.2 (M + Na)+.
Anal. Calcd for C111H117N5O7‚4H2O‚C4H8O2: C, 77.02; H, 7.47;
N, 3.91. Found: C, 77.16; H, 7.30; N, 3.67.
1.92 (24H, s), 2.30 (8H, br), 6.98 (16H, br), 7.1-7.3 (30H, m),
7.69 (1H, t, J ) 7.7 Hz), 8.07 (2H, d, J ) 7.7 Hz), 8.09 (2H, s),
8.46 (1H, s), 8.57 (1H, s), 8.60 (2H, s, NH), 9.06 (2H, s, NH),
9.19 (2H, s, NH). 13C NMR (62.9 MHz, DMSO-d6) δ 18.70 (CH3),
22.64 (CH2), 25.88 (CH2), 27.00 (CH2), 29.03 (CH2), 31.02 (CH3),
34.59 (CH2), 34.86 (Cq), 38.56 (Cq), 64.08 (Cq), 120.98 (CH),
121.01 (CH), 125.49 (CH), 125.97 (CH), 127.70 (CH), 129.39
(CH), 130.39 (CH), 130.84 (CH), 132.10 (Cq), 134.16 (Cq), 134.45
(Cq), 135.66 (Cq), 135.75 (Cq), 142.11 (Cq), 146.45 (Cq), 152.31
(Cq), 164.85 (CO), 176.86 (CO). MALDI-TOFMS (2,5-dihydroxy-
benzoic acid): 1794.6 (M + H)+, 1816.6 (M + Na)+, 1833.7 (M +
K)+. Anal. Calcd for C124H124N6O6‚5H2O‚C4H8O2: C, 77.94; H,
7.26; N, 4.26. Found: C, 77.50; H, 7.02; N, 4.14.
N,N′-(4-Tr itylph en yl)bicyclo[2.2.2]octan e-1,4-dicar boxyl-
a m id e (fr ee a xle of 12). Colorless solid. Yield: 52 mg (15%).
Mp: >320 °C. Rf 0.84 (CH2Cl2/ethyl acetate 25:1). 1H NMR (250
MHz, DMSO-d6/CDCl3 2:1) δ 1.82 (12H, s), 7.02 and 7.50 (8H,
AA′BB′, J ) 8.1 Hz), 7.1-7.25 (30H, m), 9.04 (2H, br, NH).
MALDI-TOFMS (2,5-dihydroxybenzoic acid): 833.7 (M + H)+,
855.5 (M + Na)+, 872.5 (M + K)+. Anal. Calcd for C60H52N2O2‚
3H2O: C, 81.24; H, 6.59; N, 3.16. Found: C, 80.88; H, 6.32; N,
2.99.
Syn th esis of Rota xa n e 13. A 384 mg (0.4 mmol) portion of
tetralactam 1a and 62 mg (0.4 mmol) of succinyl dichloride are
dissolved in 200 mL of CH2Cl2 and cooled to -5 °C. A solution
of 268 mg (0.8 mmol) of 4-tritylaniline (6a ) and 12 drops of
triethylamine in 200 mL of CH2Cl2 is added dropwise during 4
h. After 24 h of additional stirring the solvent is evaporated,
and the residue is purified by column chromatography [SiO2,
CH2Cl2/ethyl acetate (15:1)] to yield the rotaxane and the free
axle.
4-Tr itylp h en yl 4-(3,5-Di-ter t-bu tylben za m id o)ben zoa te
(fr ee a xle of 10b). Colorless solid. Yield: 147 mg (55%). Mp:
250 °C. Rf 0.91 (CH2Cl2/ethyl acetate 25:1). 1H NMR (250 MHz,
3
CDCl3) δ 1.36 (9H, s), 7.10 and 7.27 (4H, AA′BB′, J ) 8.8 Hz),
7.15-7.25 (15H, m), 7.64 (1H, t, J ) 1.8 Hz), 7.70 (2H, d, J )
1.8 Hz), 7.81 and 8.18 (4H, AA′BB′, 3J ) 8.9 Hz), 8.15 (1H, br,
NH).13C NMR (62.9 MHz, CDCl3) δ 31.29 (CH3), 34.96 (Cq), 64.54
(Cq), 119.43 (CH), 120.49 (CH), 121.32 (CH), 124.64 (Cq), 125.94
(CH), 126.39 (CH), 127.49 (CH), 131.02 (CH), 131.35 (CH),
132.10 (CH), 134.14 (Cq), 143.11 (Cq), 144.33 (Cq), 146.51 (Cq),
148.76 (Cq), 151.55 (Cq), 164.70 (CO), 176.21 (CO). MALDI-
TOFMS (2,5-dihydroxybenzoic acid): 672.8 (M + H)+, 694.8 (M
+ Na)+. Anal. Calcd for C47H45NO3: C, 84.02; H, 6.75; N, 2.08.
Found: C, 83.56; H, 6.73; N, 1.97.
13. Colorless solid. Yield: 157 mg (23%). Mp: >340 °C. Rf 0.19
1
(CH2Cl2/ethyl acetate 20:1). H NMR (250 MHz, CDCl3/DMSO-
d6 1:1) δ 1.27 (9H, s), 1.49 (4H, br), 1.57 (8H, br), 1.83 and 1.84
(28H, 2s + br), 2.28 (8H, br), 6.77 and 6.83 (8H, AA′BB′, 3J )
8.9 Hz), 6.88 (8H, s), 7.05-7.2 (30H, m), 7.52 (1H, t, J ) 7.7
Hz), 8.00 (2H, d, J ) 7.7 Hz), 8.06 (2H, s), 8.21 (1H, s), 8.32
Syn th esis of Rota xa n es 11 a n d 12. A 384 mg (0.4 mmol)
portion of tetralactam 1a and 0.4 mmol of adamantane-1,3-
dicarbonyl chloride or bicyclo[2.2.2]octane-1,4-dicarbonyl chloride
are dissolved in 100 mL of CH2Cl2 and cooled to -5 °C. A solution
of 268 mg (0.8 mmol) of 4-tritylaniline (6a ) and 12 drops of
triethylamine in 100 mL of CH2Cl2 is added dropwise during 4
h. After 2 h of additional stirring the solvent is evaporated, and
the residue is purified by column chromatography [SiO2, CH2-
Cl2/ethyl acetate (25:1)] to yield the rotaxanes and free axles.
11. Colorless solid. Yield: 320 mg (44%). Mp: 260 °C. Rf 0.32
(CH2Cl2/ethyl acetate 25:1). 1H NMR (250 MHz, DMSO-d6) δ 0.25
(2H, br), 1.2 (2H, br), 1.3 (8H, br), 1.36 (9H, s), 1.4-1.6 (14H,
br), 1.91 (12H, s), 1.95 (12H, s), 2.29 (8H, br), 6.95-7.35 (46H,
m), 7.67 (1H, t, J ) 7.7 Hz), 8.08 (4H, s+d, overlapped), 8.53
(1H, s), 8.62 (1H, s), 8.71 (2H, s, NH), 9.18 (2H, br, NH), 9.30
(2H, br, NH). 13C NMR (62.9 MHz, CDCl3/CD3OD 5:1) δ 18.40
(CH3), 18.48 (CH3), 22.59 (CH2), 26.07 (CH2), 27.66 (CH), 30.84
(CH3), 34.78 (CH2), 34.94 (Cq), 36.99 (CH2), 38.78 (CH2), 41.02
(Cq), 44.64 (Cq), 64.31 (Cq), 120.08 (CH), 125.65 (CH), 125.72
(CH), 127.25 (CH), 128.45 (CH), 129.15 (CH), 130.74 (CH),
130.94 (CH), 130.98 (CH), 131.01 (CH), 133.42 (C), 133.91 (Cq),
134.76 (Cq), 134.87 (Cq), 142.97 (Cq), 146.39 (Cq), 147.42 (Cq),
147.61 (Cq), 152.95 (Cq), 166.06 (CO), 166.27 (CO), 176.81 (CO).
MALDI-TOFMS (2,5-dihydroxybenzoic acid): 1821.9 (M + H)+,
1843.9 (M + Na)+. Anal. Calcd for C126H126N6O6‚H2O‚C4H8O2:
C, 81.05; H, 7.12; N, 4.36. Found: C, 80.79; H, 7.01; N, 4.42.
N ,N ′-(4-T r i t y lp h e n y l)a d a m a n t a n e -1,3-d i c a r b o x y l-
a m id e (fr ee a xle of 11). Colorless solid. Yield: 42 mg (12%).
Mp: >320 °C. Rf 0.81 (CH2Cl2/ethyl acetate 25:1). 1H NMR (250
MHz, DMSO-d6) δ 1.67 (2H, br), 1.87 (8H, br), 2.04 (2H, br),
2.16 (2H, br), 7.02 and 7.55 (8H, AA′BB′), 7.1-7.3 (30H, m), 9.23
(2H, s, NH). MALDI-TOFMS (2,5-dihydroxybenzoic acid): 859.4
(M + H)+, 881.4 (M + Na)+. Anal. Calcd for C62H54N2O2‚H2O:
C, 84.90; H, 6.43; N, 3.19. Found: C, 84.90; H, 6.14; N, 3.06.
12. Colorless solid. Yield: 180 mg (25%). Mp: >320 °C. Rf 0.44
(CH2Cl2/ethyl acetate 25:1). 1H NMR (250 MHz, DMSO-d6/CDCl3
2:1) δ 1.01 (12H, s), 1.36 (9H, s), 1.46 (4H, br), 1.53 (8H, br),
(2H, s, NH), 8.40 (1H, s), 9.16 (2H, s, NH), 9.20 (2H, s, NH). 13
C
NMR (62.9 MHz, DMSO-d6/CDCl3 2:1) δ 18.19 (CH3), 18.23
(CH3), 22.53 (CH2), 25.83 (CH2), 30.19 (CH2), 30.86 (CH3), 34.64
(CH2), 44.41 (Cq), 63.85 (Cq), 118.41 (CH), 121.74 (CH), 125.37
(CH), 125.63 (CH), 127.22 (CH), 128.70 (CH), 130.13 (CH),
130.33 (CH), 130.52 (CH), 132.07 (Cq), 132.19 (Cq), 134.00 (Cq),
134.24 (Cq), 134.75 (Cq), 135.75 (Cq), 141.15 (Cq), 146.21 (Cq),
146.84 (Cq), 147.00 (Cq), 151.76 (Cq), 164.55 (CO), 164.92 (CO),
170.23 (CO). MALDI-TOFMS (2,5-dihydroxybenzoic acid): 1736.6
(M + Na)+. FABMS (3-nitrobenzyl alcohol): 1713.0 (M + H)+.
Anal. Calcd for C118H116N6O6‚H2O‚C4H8O2: C, 80.50; H, 6.98; N,
4.62. Found: C, 80.29; H, 6.80; N, 4.76.
N,N′-(4-Tr itylp h en yl)su ccin a m id e (fr ee a xle of 13). Col-
orless solid. Yield: 96 mg (32%). Mp: 273 °C. Rf 0.33 (CH2Cl2/
1
ethyl acetate 20:1). H NMR (250 MHz, CDCl3/DMSO-d6 1:1) δ
2.60 (4H, s), 7.00 and 7.43 (8H, AA′BB′, 3J ) 8.7 Hz), 7.1-7.2
(15H, m), 9.82 (2H, s, NH). FABMS (3-nitrobenzyl alcohol): 753.4
(M + H)+. Anal. Calcd for C54H44N2O2‚0.5H2O: C, 85.12; H, 5.95;
N, 3.68. Found: C, 85.16; H, 5.89; N, 3.80.
Syn th esis of Rota xa n e 14. A mixture of 384 mg (0.4 mmol)
of tetralactam 1a and 159 mg (0.4 mmol) of di-N-succinimidyl
sebacinate17 in 100 mL of CH2Cl2 is added dropwise during 4 h
to a refluxing solution of 268 mg (0.8 mmol) of 4-tritylaniline
(6a ) and 98 mg (0.8 mmol) of N,N-dimethylaminopyridin in 100
mL of CH2Cl2. After 24
h of additional stirring at room
temperature the solvent is evaporated, and the residue is
purified by column chromatography [SiO2, CH2Cl2/ethyl acetate
(20:1)] to yield the rotaxane and the free axle.
14. Colorless solid. Yield: 80 mg (11%). Mp: 312 °C. Rf 0.35
(CH2Cl2/ethyl acetate 20:1).1H NMR (250 MHz, DMSO-d6) δ 0.76
(4H, br), 1.09 (4H, br), 1.32 (9H, s), 1.46 (4H, br), 1.55 (8H, br),
1.69 (4H, br t), 1.95 (24H, s), 2.29 (8H, br), 6.9-7.3 (46H, m),
7.61 (1H, t, J ) 7.7 Hz), 8.01 (2H, d, J ) 7.7 Hz), 8.04 (2H, s),
8.37 (1H, s), 8.50 (1H, s), 9.16 (2H, s, NH), 9.21 (2H, s, NH),
9.41 (2H, s, NH). 13C NMR (62.9 MHz, DMSO-d6, 50 °C) δ 18.27
(CH3), 22.54 (CH2), 24.38 (CH2), 25.76 (CH2), 28.32 (CH2), 30.83
(CH3), 34.62 (CH2), 35.51 (CH2), 44.41 (Cq), 63.87 (Cq), 118.69
(CH), 125.44 (CH), 125.72 (CH), 126.92 (CH), 127.39 (CH),
130.23 (CH), 130.41 (CH), 132.13 (Cq), 134.23 (Cq), 134.29 (Cq),
134.36 (Cq), 134.54 (Cq), 136.27 (Cq), 141.01 (Cq), 146.28 (Cq),
(17) Kondo, M.; Shimizu, Y.; Murata, A. Agric. Biol. Chem. 1982,
46, 913-918.

7242 J . Org. Chem., Vol. 64, No. 19, 1999
Notes
146.62 (Cq), 151.95 (Cq), 164.92 (CO), 165.11 (CO), 171.94 (CO).
MALDI-TOFMS (2,5-dihydroxybenzoic acid): 1799.0 (M + H)+,
1820.9 (M + Na)+.
Ack n ow led gm en t. The authors have to thank their
co-workers Dr. C. Heim, Dr. S. Braschohs, R. Schmieder,
and Dr. G. Nuding for providing some of the compounds.
Furthermore, we thank Prof. Dr. R. N. Dominey,
University of Richmond, for his valuable suggestions for
the final version of the manuscript. This work was
supported by Deutsche Forschungsgemeinschaft (Vo
145/47-1).
N,N′-(4-Tr itylp h en yl)seba cin a m id e (fr ee a xle of 14).
Colorless solid. Yield: 63 mg (11%). Mp: 294 °C. Rf 0.55 (CH2-
Cl2/ethyl acetate 20:1). 1H NMR (250 MHz, DMSO-d6) δ 1.26
(8H, br), 1.55 (4H, br), 2.25 (4H, t, J ) 7.3 Hz), 7.02 and 7.47
(8H, AA′BB′,), 7.12 (12H, d, 3J ) 7.4 Hz), 7.18 (6H, t, J ) 7.0
Hz), 7.28 (12H, t), 9.86 (2H, s, NH). MALDI-TOFMS (2,5-
dihydroxybenzoic acid): 837.7 (M + H)+, 859.7 (M + Na)+. Anal.
Calcd for C60H56N2O2‚0.5H2O: C, 85.17; H, 6.79; N, 3.31. Found:
C, 85.00; H, 6.74; N, 3.26.
J O990042+