Synthesis, Conformational Analysis, and Binding Properties of Molecular Clips with Two Different Side Walls

Article abstract of DOI:10.1021/jo961382n

A new general route toward the synthesis of diphenylglycoluril clips with two different side walls starting from the new precursor 6b and the known compound 2b is described. A variety of clips are accessible in this way, some of them containing metal binding ligand systems, viz. phenanthroline, pyridine, salophen, and porphyrin for future applications as supramolecular catalysts. The physical and binding properties of the new clips are presented and discussed.

Full text of DOI:10.1021/jo961382n

2234
J . Org. Chem. 1997, 62, 2234-2243
Syn th esis, Con for m a tion a l An a lysis, a n d Bin d in g P r op er ties of
Molecu la r Clip s w ith Tw o Differ en t Sid e Wa lls
J oost N. H. Reek, J ohannes A. A. W. Elemans, and Roeland J . M. Nolte*
Department of Organic Chemistry, NSR Center, University of Nijmegen,
Toernooiveld 6525 ED Nijmegen, The Netherlands
Received J uly 22, 1996X
A new general route toward the synthesis of diphenylglycoluril clips with two different side walls
starting from the new precursor 6b and the known compound 2b is described. A variety of clips
are accessible in this way, some of them containing metal binding ligand systems, viz. phenan-
throline, pyridine, salophen, and porphyrin for future applications as supramolecular catalysts.
The physical and binding properties of the new clips are presented and discussed.
In tr od u ction
electrostatic interactions, π-π stacking interactions, and
metal-to-ligand bonding. One of the more promising
types of receptor molecules which are capable of binding
guests in organic solvents are the tweezer-like or clip-
shaped receptors. Zimmerman8 and Whitlock9 have
constructed excellent examples of this type of molecules,
showing high substrate binding and selectivity. The next
step, however, to combine these types of receptors with
a catalytically active site has received considerably less
attention. The most commonly used catalysts described
in the literature are porphyrins and salophenes, the
former species often being found in natural enzymes.
Several examples of bridged, capped, and fenced porphy-
rins as catalysts giving remarkable selectivities have
been reported.10 Only in a limited number of systems,
is the porphyrin located nearby a substrate binding
site.11-13
There is currently great interest in the fields of host-
guest chemistry and in catalysis of reactions using simple
enzyme mimics.1 The focus of this interest has been
primarily on the design and construction of molecules
possessing a binding site for a substrate, which is
positioned nearby a catalytically active center. In the
case of enzymes, the enzyme-substrate complex forma-
tion is generally dominated by hydrophobic effects with
additional, relatively weak interactions such as hydrogen
bonding, π-π stacking, and dipolar interactions used to
control substrate selectivity and orientation. The shape
complementarity of the receptor site and the aforemen-
tioned weak interactions are of fundamental importance
for achieving substrate selectivity and regio- and enan-
tioselectivity in the reaction. Early research into this
area has revealed that cyclodextrins are ideal building
blocks for the construction of simple enzyme-like cata-
lysts.2 As in natural enzymes, substrate binding in these
mimics is dominated by hydrophobic interactions.3 Simple
modifications of the cyclodextrin molecules with basic
functionalities has provided catalysts that are active
toward ester hydrolysis and transesterification reactions.4
A more recent example of a water soluble molecule with
a binding site is that of Diederich’s cyclophane,5 which
when functionalized with a thiazolium6 or a porphyrin
group7 proved also to be a good enzyme mimic. Organic
chemists are not, like nature, confined to the use of water
as a solvent, and consequently the enzyme approach can
also be applied to molecular systems that are soluble in
organic solvents. In these cases the main forces contrib-
uting to the complex stability are hydrogen bonding,
One of the major goals of research in our group has
been the design and synthesis of new types of cleft-shaped
host molecules that can be functionalized with catalyti-
cally active components and used consequently as enzyme
mimics. Previous work toward this goal has led to the
development of clip,14 and basket-shaped15 molecules
(8) (a) Zimmerman, S. C. Bioorganic Chemistry Fontriers 2;
Springer-Verlag: Berlin 1991; pp 33-74 and references cited therein
(b) Zimmerman, S. C.; VanZyl, C. M. J . Am. Chem. Soc. 1987, 109,
7894. (c) Zimmerman, S. C.; VanZyl, C. M.; Hamilton, G. S. J . Am.
Chem. Soc. 1989, 111, 1373.
(9) (a) Whitlock B. J .; Whitlock, H. W. J . Am. Chem. Soc. 1994, 116,
2301. (b) Whitlock B. J .; Whitlock, H. W. J . Am. Chem. Soc. 1990, 112,
3910.
(10) Collman. J . P.; Zhang, X.; Lee, V. J .; Uifelman, E. S.; Brauman,
J . I. Science 1993, 261, 1404 and references cited therein.
(11) (a) Nagasaki, T.; Fujisima, H.; Shinkai, S. Chem. Lett. 1994,
989. (b) Gunter, M. J .; J ohnston, M. R.; Skelton, B. W.; White, A. H.
J . Chem. Soc., Perkin Trans. 1 1994, 1009. (c) Gunter, M. J .; Hockless,
D. C. R.; J ohnston, M. R.; Skelton, B. W.; White, A. H. J . Am. Chem.
Soc. 1994, 116, 4810. (d) Collman. J . P.; Zhang, X.; Herrmann, P. C.;
Uffelman, E. S.; Boitrel, B.; Straumanis, A.; Brauman, J . I. J . Am.
Chem. Soc. 1994, 116, 2681. (e) Kuroda, Y.; Kato, Y.; Ito, M.; Hasegawa,
J .-y.; Ogoshi, H. J . Am. Chem. Soc. 1994, 116, 10338. (f) Bonar-Law,
R. P.; Mackay, L. G.; Sanders, J . K. M. J . Chem. Soc., Chem. Commun.
1993, 456.
(12) (a) Anderson, H. L.; Bashall, A.; Henrick, K.; McPartlin, M.;
Sanders, J . K. M. Angew. Chem. 1994, 106, 445. (b) Walter, C. J .;
Anderson, H. L.; Sanders, J . K. M. J . Chem. Soc., Chem. Commun.
1993, 458. (c) Mackay, L. G.; Wylie, R. S.; Sanders, J . K. M. J . Am.
Chem. Soc. 1994, 116, 3141.
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) Feiters, M. C. “Supramolecular Catalysis” In Comprehensive
Supramolecular Chemistry; Lehn, J . M., Ed.; in press.
(2) (a) Breslow, R. Isr. J . Chem. 1992, 32, 23. (b) Breslow, R. Recl.
Trav. Chim. Pays-Bas 1994, 113, 493. (c) Akkaya, E. U.; Czarnik, A.
W. J . Am. Chem. Soc. 1988, 110, 8553. (d) Menger, F. M.; Ladika, M.
J . Am. Chem. Soc. 1987, 109, 3145. (e) Bender, M. L.; Komiyama, M.
Cyclodextrin Chemistry; Springer: Berlin, 1978. (f) Breslow, R. Science
1982, 218, 532. (g) Tabushi, I. Pure Appl. Chem. 1986, 58, 1529. (h)
Weber, L.; Hommel, R.; Behling, J .; Haufe, G.; Hennig, H. J . Am. Chem.
Soc. 1994, 116, 2400. (i) Kuroda, Y.; Hiroshige, T.; Sera, T; Shiroiwa,
Y.; Tanaka, H. Ogoshi, H. J . Am. Chem. Soc. 1989, 111, 1912.
(3) Cramer, F. Einschlussverbindungen; Springer: Berlin, 1954.
(4) Anslyn, E.; Breslow, R. J . Am. Chem. Soc. 1989, 111, 8931.
(5) Diederich, F. Cyclophanes; Royal Society of Chemistry: Cam-
bridge, 1991.
(13) Cacciapaglia, R.; Casnati, A.; Mandolini, L.; Ungaro, R. J . Am.
Chem. Soc. 1992, 114, 10956.
(14) (a) Sijbesma, R. P.; Wijmenga, S. S.; Nolte, R. J . M. J . Am.
Chem. Soc. 1992, 114, 9807. (b) Smeets, J . W. H.; Sijbesma, R. P.; van
Dalen, L.; Spek, A. L.; Smeets, W. J . J .; Nolte, R. J . M. J . Org. Chem.
1989, 54, 3710. (c) Sijbesma, R. P.; Kentgens, A. P. M.; Nolte, R. J . M.
J . Org. Chem. 1991, 56, 3199. (d) Sijbesma, R. P.; Kentgens, A. P. M.;
Lutz, E. T. G.; van der Maas, J . H.; Nolte, R. J . M. J . Am. Chem. Soc.
1993, 115, 8999.
(6) Diederich, F.; Lutter, H.-D. J . Am. Chem. Soc. 1989, 111, 8438.
(7) (a) Benson, D. R.; Valentekovich, R.; Diederich, F. Angew. Chem.
1990, 102, 213. (b) Benson, D. R.; Valentekovich, R.; Knobler, C. B.;
Diederich, F. Tetrahedron 1991, 47, 2401.
S0022-3263(96)01382-5 CCC: $14.00 © 1997 American Chemical Society

Molecular Clips with Two Different Side Walls
J . Org. Chem., Vol. 62, No. 7, 1997 2235
with a second side wall will result in the desired
compounds. In order to synthesize clip molecules func-
tionalized with one ligand system, the monowalled spe-
cies have to be nitrated before the second wall is attached
(vide infra). These steps will be described later.
Mon ow a lled Molecu les Ba sed on DP G. To obtain
monowalled host 7, cyclic ether 1 was reacted with 1
equiv of 1,4-dimethoxybenzene (1,4-DMB) in a mixture
of acetic anhydride and TFA under a variety of different
reaction conditions. In all cases the reaction product was
a 1:1 mixture of 1 and 3a , probably because the acetate
functions in the intermediate 8 are activated by the
attached aromatic wall toward a further amido alkylation
reaction compared to the tetraacetate intermediate 2a .
Another possibility is that the first attached wall has a
favorable preorganization effect on the second 1,4-DMB
molecule. In order to overcome this problem, a new
starting compound, 6b, which has two sites of differing
reactivity toward Friedel-Crafts alkylation was synthe-
sized. Compound 6b was obtained from 1 in two steps:
(i) a partial reaction of 1 with acetic anhydride using
p-toluenesulfonic acid as a catalyst and subsequent
separation of 6a from 1 by column chromatography,
yielding 6a in 65%; (ii) substitution of the acetyl groups
with chloride groups by stirring 6a overnight in a 1:1
mixture of CH2Cl2 and thionyl chloride. This gave
crystalline 6b (92% yield) which was moisture sensitive.
Reaction of 6b with 1,4-DMB in 1,2-dichloroethane
with SnCl4 as a catalyst at both room temperature and
at 0 °C again resulted in mixtures of 1 and 3a as
products. The reaction was performed at lower temper-
ature, in order to better differentiate the reactivity of the
sites of 6b. To a 1:1 mixture of 6b and 1,4-DMB in 1,2-
dichloroethane at -35 °C was added SnCl4, and the
mixture was allowed to warm slowly to 0 °C overnight.
The precipitate obtained was found to be 7 (88% yield).
A similar reaction of the tetrachloro derivative 2b yielded
a mixture of 1, 7, and 3a (molar ratio 1:4:1), which could
be separated by column chromatography to give pure 7
(58%). An alternative approach to obtain 7 was by
performing the reaction at room temperature but in high
dilution. Slow addition of a solution of 1,4-DMB to an
1,2-dichloroethane solution of 2b and SnCl4 again yielded
a mixture of 1, 7, and 3a (1:4:1), which yielded 7 (52%
after column chromatography).
2,7-Dimethoxynaphthalene (2,7-DMN) and 1,4-dime-
thoxynaphthalene (1,4-DMN) are less reactive toward
attack by 2b than 1,4-DMB. An equimolar mixture of
2b and 2,7-DMN in 1,2-dichloroethane containing 4 equiv
of SnCl4 was heated under reflux to yield 9 in 71% after
column chromatography. A similar reaction of 2b with
1,4-DMN yielded 10 in 42%.
Molecu la r Clip s w ith Tw o Differ en t Sid e Wa lls.
The monowalled molecules 7, 9, and 10 could now be used
as starting materials for the preparation of several new
clips containing two different aromatic side walls. Heat-
ing a mixture of 7 with hydroquinone in 1,2-dichloroet-
hane with p-toluenesulfonic acid as a catalyst yielded 13
in 73%. This compound, which is insoluble in most
organic solvents, was converted into a bright red com-
pound 14 by aerial oxidation in DMSO using Cu2Cl2 as
a catalyst (yield 77%). Reactions of 7 and 9 with 1,4-
DMN in mixtures of acetic anhydride and TFA yielded
15 and 18 in 70 and 65%, respectively. Analogous
reactions of 9 and 10 with 1,4-DMB yielded 17a and 15
in 94 and 97%, respectively.
F igu r e 1. X-ray structure of the double nickel(II) salophene
functionalized molecular clip (see ref 18).
based on diphenylglycoluril which were found to be ideal
hosts for hydroxybenzene substrates. Subsequent func-
tionalization of these baskets with metal centers posi-
tioned above the cavity via flexible spacers gave host
molecules which were still able to bind dihydroxyben-
zenes, but in addition showed catalytic activity giving
substrate selectivity16 and enhancement of reaction
rates.17 Another approach used to construct biomimetic
catalysts was to functionalize the side walls of a molec-
ular clip with two metal salophene groups (Figure 1).18
The obtained clip was unable, unfortunately, to bind
guest molecules due to the steric hindrance of the
methoxy groups blocking the cavity. In order to overcome
the steric hindrance caused by the close proximity of two
functionalized walls, it was necessary to design clip
molecules with two different (aromatic) side walls which
would facilitate the monofunctionalization with a metal
center. In this paper the synthesis, characterization, and
preliminary binding studies of these new clip molecules
are described.
Resu lts a n d Discu ssion
Syn th esis. Previously developed starting compounds
derived from diphenylglycoluril (DPG) which have been
used in the synthesis of other molecular receptors are
cyclic ether 114b and the tetraacetoxy and the tetrachloro
derivatives 2a and 2b (Chart 1).14a Clip 3a can be
synthesized from 1 by means of an acid-catalyzed amido
alkylation reaction, and clips 3b, 4, and 5a are accessible
from the more reactive compound 2b.
The first step in the synthesis of asymmetrically
substituted clip molecules is the preparation of a monow-
alled intermediate. Subsequent reaction of this species
(15) Sijbesma, R. P.; Nolte, R. J . M. J . Org. Chem. 1991, 56, 3122.
(16) (a) Coolen, H. K. A. C.; van Leeuwen, P. W. N. M.; Nolte R. J .
M. Angew. Chem. 1992, 31, 905. (b) Coolen, H. K. A. C.; Meeuwis, J .
A. M.; van Leeuwen, P. W. N. M.; Nolte, R. J . M. J . Am. Chem. Soc.
1995, 117, 11906.
(17) Martens, C. F.; Klein Gebbink, R. J . M.; Feiters, M. C.; Nolte,
R. J . M. J . Am. Chem. Soc. 1994, 116, 5667.
Nitration reactions were carried out in order to obtain
clip molecules functionalized with a catalytic side wall.
(18) Gosling, P. A.; Sijbesma, R. P.; Spek, A. L.; Nolte, R. J . M. Recl.
Trav. Chim. Pays-Bas 1993, 112, 404.

2236 J . Org. Chem., Vol. 62, No. 7, 1997
Reek et al.
Ch a r t 1

Molecular Clips with Two Different Side Walls
J . Org. Chem., Vol. 62, No. 7, 1997 2237
Ch a r t 1 (Con tin u ed )
Stirring compound 7 in acetic anhydride with 2 equiv of
nitric acid for 16 h gave the mononitro compound 11a as
a crystalline precipitate in 80% yield. The analogous
reaction with a mixture of 1, 7, and 3a (molar ratio 1:4:
1) gave a precipitate which was proved to be pure 11a
(yield: 80% based on 7). Subsequent reaction of 11a in
acetic anhydride with 4 equiv of nitric acid yielded the
dinitro compound 11b in 96%, after purification by
column chromatography. Dinitro clip 16a was prepared
in 96% yield by amido alkylation of 11b with 1,4-DMB
in acetic anhydride/TFA. Several nitration reactions
with 17a were carried out in order to obtain dinitro clip
17b. The clip molecule decomposed under the conditions
necessary to nitrate the 1,4-DMB wall to give 2,7-
dimethoxy-1,8-dinitronaphthalene as a side product.
Compound 11b was reacted, therefore, with acetic acid
and p-toluenesulfonic acid to give compound 12a , which
was treated subsequently with thionyl chloride in CH2-
Cl2 to give 12b. This compound was now sufficiently
reactive to undergo a Friedel-Crafts reaction with 2,7-
DMN to yield 17b in 60% yield.
respectively. The condensation reaction of 16b and 2,2′-
pyridil or porphyrin diketone 24 in pure dichloromethane
resulted in significantly higher yields (52 and 92%,
respectively). A clip molecule functionalized at one side
with a salophene unit was obtained after a template
condensation reaction of 16b with salicylaldehyde and
Ni(OAc)2‚4H2O, yielding 25 in 66% yield. Monofunction-
alized clip molecules having an opposing 2,7-DMN side
wall were obtained by similar condensation reactions
using 17c as the diamine precursor, resulting in clip
molecules 26-28 (yields 31, 80, and 26%, respectively).
NMR Con for m a tion a l An a lysis. It has been shown
previously14a by our group that a naphthalene moiety
which is connected to the DPG framework at the 1- and
8-positions can adopt two orientations: (a) upward with
respect to the phenyl ring on the convex side of the DPG
unit (anti) and (b) downward (syn) with respect to this
ring. Compound 4 which has two napthalene moieties
connected exists in three conformations in solution, which
interconvert slowly on the NMR time scale, syn-syn
(7.7%), syn-anti (89.6%) and anti-anti (2.7%).
Dinitro compounds 11b, 16a , and 17b were reduced
to the corresponding diamines, 11c, 16b, and 17c, using
triethylammonium formate19 as a hydrogen donor with
Pd on carbon as a catalyst in a mixture of THF and
methanol. These compounds were found to be very
sensitive to oxidation and were used without further
purification for subsequent synthesis.
Clip Molecu les F u n ction a lized w ith Ca ta lytic
Sid e Wa lls. All clips containing one or two walls
functionalized with a ligand were obtained by a conden-
sation reaction of 11c, 16b, 16d , or 17c with a diketone
precursor or with salicylaldehyde. Heating 11c with 1,-
10-phenanthroline-5,6-quinone20 in a (1:1:1 (v/v)) mixture
of MeOH/THF/CH2Cl2 over molecular sieves (3 Å) yielded
19 in 79% after purification by column chromatography.
Similar reactions of 16b with 1,10-phenanthroline-5,6-
quinone, 2,2′-pyridil, and porphyrin diketone 24a 21 gave
compounds 21, 22, and 23a in 75, 31, and 28% yields,
Compounds 9, 17a , and 18, which have one naphtha-
lene wall connected at the 1- and 8-positions, were
expected to exist in solution in only two conformations,
viz. syn and anti. The 400 MHz 1H NMR spectra of these
compounds in CDCl3 at 298 K confirmed this. Nearly
all signals of the respective conformers could be assigned
with the help of COSY spectra (see Table 1). The
procedure that was followed for this assignment was
similar to that described previously for 4.14a The shield-
ing effects of aromatic rings can be estimated with the
help of the J ohnson and Bovey tables.22 It can be shown
that the signals of the protons of the phenyl groups of
the diphenylglycoluril framework on the syn side of one
conformer are shifted upfield relative to the proton
signals on the anti side. This method enables full
assignment of the AX quartets of the NCH2 protons and
the signals of the wall protons for each of the conformers.
The relative abundance of the different conformers of 9,
(19) Cortese, N. A.; Heck, R. F. J . Org. Chem. 1977, 42, 3491 and
references cited therein.
(20) (a) Smith, G.; Cagle, F. W., J r. J . Org. Chem. 1947, 12, 781. (b)
Koft, E.; Case, F. H. J . Org. Chem. 1962, 27, 865. (c) Dickeson, J .;
Summers, L. Aust. J . Chem. 1970, 23, 1023.
(21) Crossley, M. J .; King, L. J . J . Chem Soc., Chem. Commun. 1984,
920.
(22) J ohnson, C. S., J r.; Bovey, F. A. J . Chem. Phys. 1958, 29, 1012.
(23) Hunter, C. A.; Sanders, J . K. M. J . Am. Chem. Soc. 1990, 112,
5525.

2238 J . Org. Chem., Vol. 62, No. 7, 1997
Reek et al.
F igu r e 2. Binding of a resorcinol guest molecule by an “induced fit” mechanism in a clip containing an 1,8-connected naphthalene
side wall.
Ta ble 1. Assign m en t of 1H NMR Sign a ls to th e
In addition to these model compounds, the conforma-
Con for m er s of 9, 17a , a n d 18a
tional behavior of the monofunctionalized clip molecules
26-28 was also studied by 1H NMR (see Table 2). These
9
17a
18
molecules are important with respect to the overall goal
of developing biomimetic catalytic systems. They were
found to exist in two conformers with the syn conformers
dominating: 68% for 26, 68% for 27, and 55% for 28.
Bin d in g P r op er t ies. It is known from our earlier
studies that molecular clip 3a is a good receptor for the
complexation of dihydroxybenzenes, whereas 5a is unable
to bind such guests.14d This lack of binding of guest
molecules was ascribed initially to the methoxy groups
on the walls of 5a which point inside the cavity and block
the carbonyl functions from forming hydrogen bonds.
Further studies indicate that, in addition to this steric
effect, there is an unfavorable, i.e. repulsive, π-π inter-
action between the aromatic guest and the naphthalene
side walls which also results in a decrease in binding
(vide infra).
Complexation studies with the guest olivetol (1,3-
dihydroxy-5-pentylbenzene) were performed in order to
obtain further insight into the influence of two different
aromatic walls in the clip molecule, upon host-guest
binding. The association constants (Ka’s) and complex-
induced shift (CIS) values for a series of related clip mole-
cules were determined by 1H NMR titrations as described
previously.14d The trends in binding affinity of olivetol
to selected clips are shown in Table 3. It can be seen
that a large drop in Ka is observed upon going from host
molecules 3a to 15 to 5a . This highlights the fact that
an 1,4-DMN wall (which can be considered as a function-
alized 1,4-DMB wall) is unfavorable for guest binding
compared with an 1,4-DMB wall. By comparing the asso-
ciation constant between olivetol and clip 3a with that
of clip 15 it can be seen that the presence of one 1,4-
DMN side wall in a clip considerably reduces the binding
strength (25×), but does not totally block the cleft for
binding. The binding of olivetol to cyclic ether 1 (Ka )
25 M-1) increases when an 1,4-DMB wall is attached to
this molecule (7, Ka ) 40 M-1), but decreases when this
wall is an 1,4-DMN aromatic surface (10, Ka < 1 M-1).
Clip molecules 17a and 18 are able to bind an olivetol
guest by an induced fit mechanism. The 2,7-DMN wall
flips upon complexation of the guest molecule as depicted
in Figure 2. The association constants for clips 17a and
proton signal
anti
syn
anti
syn
anti
syn
NCH2O
5.37
5.66
outb
(11.0) (11.0)
4.29 4.44
(11.0) (11.0)
NCH2O
inb
NCH2Ph
outb
5.39
5.68
(15.8) (15.8)
3.85 3.74
(15.8) (15.8)
5.98 6.12
NCH2Ph
inb
NCH2Napht (2,7) 5.98
outb
6.20
5.97
6.15
(16.3) (16.5) (16.4) (16.4) (16.4) (14.8)
NCH2Napht (2,7) 4.19
5.11
4.10
4.95
4.09
d
5.63
(16.0) (15.9)
3.84 3.93
(16.0) (15.9)
4.02
3.90
d
4.96
(14.8)
5.82
inb
(16.3) (16.5) (16.4) (16.4)
NCH2Napht (1,4)
outb
NCH2Napht (1,4)
inb
OCH3
4.11
3.97
4.07
3.75
d
d
d
6.12
7.14
(9.1) (9.1)
7.62 7.26
(9.1) (9.1)
3.95
3.93
6.46(s)
6.13(s)
6.26(s)
6.85
4.25
3.96
6.50(s)
6.16(s)
6.28(s)
Ph H-2,6c
Ph H-3,5c
Ph H-4c
d
d
d
6.42(s)
6.13(s)
6.25(s)
d
d
Ph H-2,3e
Napht H-3 (2,7)
7.19
6.90
6.88
7.11
6.88
(9.0) (9.0)
7.74 7.30
(9.0) (9.0)
(8.9) (8.9)
7.57 7.26
(8.9) (8.9)
7.95
7.41
Napht H-4 (2,7)
Napht H-5,8 (1,4)
Napht H-6,7 (1,4)
8.11
7.51
a
Shifts are in ppm; J couplings (Hz) in parentheses; the
designations (s) and (a) are used for the phenyl rings syn and anti
b
with respect to the side walls. The designations in and out are
used as indicated in Chart 1. c Protons of the glycoluril framework.
No assignment could be made. e Protons of the 1,4-dimethoxy-
d
benzene side wall.
17a , and 18 were determined by integration of these
signals: 23% of the molecules of 9 were in the syn
conformation and 77% in the anti conformation in CDCl3
at 298 K. In the case of 17a , these values were 85 and
15%, and in the case of 18 76 and 24%, respectively. This
result is in agreement with the previously proposed idea
that clip molecules with naphthalene walls connected
at the 1,8-positions preferentially adopt a conformation
in which the walls are optimally exposed to solvent
molecules.14a For compound 4 this is achieved with the
syn-anti conformation, for compound 9 with the anti
conformation, and for compounds 17a and 18 with the
syn conformation. More details concerning these confor-
mations will be presented in a separate paper.24
(24) Reek, J . N. H.; Elemans, J . A. A. W.; Engelkamp, H.; Rowan,
A. E.; Nolte, R. J . M. J . Am. Chem. Soc., submitted.

Molecular Clips with Two Different Side Walls
J . Org. Chem., Vol. 62, No. 7, 1997 2239
Ta ble 2. Assign m en t of 1H NMR Sign a ls to th e Con for m er s of 26, 27, a n d 28a
26 27
28
proton signal
anti
syn
anti
syn
anti
syn
NCH2Ph
5.50
(15.9)
3.88
(15.9)
5.98
(15.9)
4.09
(15.9)
4.03
3.52
5.65
5.89
(16.4)
3.96
(16.4)
6.04
(16.4)
4.12
(16.4)
4.34
4.05
6.08
(15.9)
4.01
(15.9)
6.17
(14.9)
4.98
(14.9)
4.72
5.85
(15.0)
3.82
(15.0)
5.58
(15.0)
3.96
(15.0)
3.96
6.13
(15.0)
3.95
(15.0)
4.80
(15.0)
2.70
(15.0)
3.91
outb
(15.8)
3.86
(15.8)
6.15
(14.7)
4.98
(14.7)
3.97
3.81
6.49
(s)
6.19
(s)
6.29
(s)
6.89
(9.0)
7.28
(9.0)
NCH2Ph
inb
NCH2Napht (2,7)
outb
NCH2Napht (2,7)
inb
OCH3
3.99
6.54
3.55
7-7.3
3.85
6.75(s)
Ph H-2,6c
7.36-6.95
7.32-6.98
7.23(a)
6.15(s)
6.85(a)
6.60(s)
7.10(a)
6.8-7.3
Ph H-3,5c
7.36-6.95
7.32-6.98
7.32-6.98
6.25
7-7.3
Ph H-4c
6.60
6.30
(7.3)
6.90
(9.0)
7.28
(9.0)
7-7.3
Napht H-3 (2,7)
Napht H-4 (2,7)
7.17
(9.0)
7.59
(9.0)
7.02)
(8.8)
7.47
6.8-7.3
6.8-7.3
6.8-7.3
(8.8)
ArH
ArNCHAr
PhenanH
7.36-6.95
9.04
7.36-6.95
9.26
9.50
9.22
7.72
9.67
9.29
7.84
porphyrin âH
porphyrin âH
8.94
8.67
(5.0)
8.94
8.67
(5.0)
8.77
8.77
porphyrin pyr H
porphyrin ArH
porphyrin ArCCH
-2.68
7.5-8.3
1.5-1.7
-2.68
7.5-8.3
1.5-1.7
a
Shifts are in ppm; J couplings (Hz) in parentheses; the designations (s) and (a) are used for the phenyl rings syn and anti with
respect to the side walls. The designations in and out are used as indicated in Chart 1. c Protons of the glycoluril framework.
b
Ta ble 3. Associa tion Con sta n ts a n d Com p lex-In d u ced
unfavorable π-π stacking interactions. These unfavor-
Sh ift Va lu es of Com p lexes betw een Olivetol a n d
able π-π interactions are caused by a repulsive electro-
Differ en t Clip sa
static interaction according to calculations using the
Ka/M-1
CIS/ppmb
clip
Ka/M-1
CIS/ppmb
Hunter and Sanders model23 (see also ref 25 ). The for-
mation of the hydrogen bonds between host and guest
forces the guest into a geometry in which the π-π inter-
action with the aromatic side walls is very unfavorable.
clip
3a
15
5a
1
1500
55
<1
25
-0.51
-0.43
20
21
22
23a
5b
3b
25
26
<1
210
125
-0.36
-0.31
-0.34
30
Comparison of the complex-induced shift (CIS) value
of clip 15 (-0.43 ppm) with that of 3a (-0.51 ppm),
indicates that in both complexes the guest molecule is
positioned in a similar orientation. Calculations were
carried out with a computer program based on the
J ohnson and Bovey tables of ring current shifts,22 which
suggested that the guest is less deeply bound in the cavity
of clip 15 than in the cavity of clip 3a .14d This might be
important when a guest molecule has to be bound nearby
a catalytically active site, e.g. a metal center bound to
ligands 19-23.
The binding properties of the ligand functionalized
molecular clips 19-26 are of interest with respect to the
aims outlined in the introduction. The monophenan-
throline clip 21 is capable of binding olivetol (Ka ) 210
M-1), whereas the diphenanthroline clip 20 is not a good
host (Ka < 1 M-1). This is in line with the binding results
obtained with clip molecules 3a , 5a , and 15 (vide supra)
and is due to the repulsive nature of the two large
electronegative side walls of 20, and the steric effects of
the methoxy groups which partly shield the carbonyl
groups. Porphyrin clip 23a and dipyridine clip 22 are
also capable of binding olivetol in their clefts (Ka ) 30
and 125 M-1, respectively). The observed binding con-
stants are lower than the binding constant of monophen-
7
40
-0.34
60d
10
17a
18
19
<1
175d,e
920
1060c
90c
<1
-0.44f
-0.40f
1200
a
b
The errors in the association constants are 10-30%. CIS
values of the 1,4-dimethoxybenzene side walls. c Value taken from
d
ref 24. Association constant of the complex with resorcinol.
e Value taken from ref 25. f CIS values of the imine protons.
18 were determined by following the ratio of conformers
as a function of the guest concentration.14a These experi-
ments also revealed that the 1,4-DMN wall is very
unfavorable for binding. A drop in association constant
from Ka ) 1060 M-1 (17a ) to 90 M-1 (18) was observed
when the 1,4-DMB wall in the clip molecule was replaced
by an 1,4-DMN wall (Table 3). Since the change to an
1,4-DMN wall had such a great influence upon the host-
guest binding, it was decided to perform binding studies
with 5b, a molecule with naphthalene walls but without
methoxy groups. In this case resorcinol (1,3-dihydroxy-
benzene) was chosen as the guest molecule in order that
a comparison with previous studies could be made.14d Clip
molecule 5b was able to bind resorcinol (Ka ) 70 M-1),
but with a lower binding constant than was found for
the clip with two benzene walls 3b (Ka ) 175 M-1). When
the methoxy groups of clip molecule 5a are removed, the
cleft is no longer blocked; however, the binding is still
relatively weak (compared with that of 3b) because of
(25) Reek, J . N. H.; Priem, A. H.; Elemans, J . A. A. W.; Engelkamp,
H.; Rowan, A. E.; Nolte, R. J . M. J . Am. Chem. Soc., submitted.

2240 J . Org. Chem., Vol. 62, No. 7, 1997
Reek et al.
described elsewhere. 1,10-Phenanthroline-5,6-quinone was
synthesized from 1,10-phenanthroline monohydrate according
to literature procedures.20 17,18-Dioxoporphyrins 24a and 24b
were kindly provided by Prof. M. J . Crossley.21
anthroline clip 21 due to steric effects. In clip 22 the
pyridyl groups are positioned orthogonally to the wall of
the cleft, leading to steric congestion when the guest is
bound. Porphyrin clip 23a contains phenyl groups at-
tached to the porphyrin ring which are pointing slightly
into the cleft, as is evident from the X-ray structure of
this molecule.26 These phenyl groups cause steric repul-
sion, resulting in a lower association constant. Monow-
alled clip molecule 19 is not able to bind olivetol, which
is in agreement with the binding properties of 10. The
CIS values of the complexes between the clips 21, 22,
and 23 and olivetol suggest that the guest is bound with
approximately the same geometry but less deeply than
in clip 3a .14d
6,8,15,16b,16c,17-Hexa h yd r o-16b,16c-d ip h en yl-7H,16H-
6a ,7a ,15a ,16a -tetr a a za n a p h th o[5,6]a zu len o[2,1,8-ij]n a p h -
th o[f]a zu len e-7,16-d ion e (5b). To a suspension of 900 mg
(16 mmol) of KOH in 2 mL of DMSO was added 300 mg (1.0
mmol) of diphenylglycoluril and 650 mg (2.7 mmol) of R,R′-
dibromo-2,3-dimethylnaphthalene. The mixture was stirred
for 16 h and then poured into 20 mL of water. The compound
was extracted with 20 mL of CH2Cl2, and the organic layer
was washed with aqueous 1 N NaOH and water and dried over
MgSO4. After evaporation of the solvent, the compound was
purified by column chromatography (eluent CH2Cl2) and
recrystallization from CHCl3, yielding 184 mg of white powder
(31%): mp >310 °C; 1H NMR (CDCl3) δ 7.70 (s, 4H, NaphtH),
7.70-7.60 and 7.45-7.30 (2m, 8H, NaphtH), 7.18 (s, 10H,
ArH), 5.01 and 4.27 (2d, 8H, NCH2Ar, J ) 16.0 Hz); FAB-MS
m/ z 599 (M + H)+. Anal. Calcd for C40H30N4O2: C, 80.25; H,
5.05; N, 9.36. Found: C, 80.56; H, 5.11; N, 8.99.
Acetic Acid [3-(Acetoxym eth yl)tetr a h yd r o-1,4-d ioxo-
2a ,7b-d ip h en yl-6-oxa -2,3,4a ,7a -tetr a a za cyclop en ta [cd ]in -
d en -2-yl]m eth yl Ester (6a ). A suspension of 3.18 g (8.40
mmol) of 1 and 80 mg (0.42 mmol) of p-toluenesulfonic acid
monohydrate in 15 mL of acetic anhydride was heated to
reflux. After the mixture became clear, it was instantly cooled
in an ice bath. Diethyl ether (15 mL) was added, and the
resulting precipitate was filtered off, washed with diethyl
ether, and dried under vacuum. After column chromatography
(CH2Cl2/MeOH, 99:1 v/v), 2.62 g (65%) of 6a was obtained as
a white solid: mp 228 °C; IR (KBr) 1756, 1737 (CdO), 1237
(COC); 1H NMR (CDCl3) δ 7.20-6.95 (m, 10H, ArH), 5.65 and
4.47 (2d, 4H, NCH2OAc, J ) 11.4 Hz), 5.62 and 5.33 (2d, 4H,
NCH2O, J ) 11.1 Hz), 2.07 (s, 6H, COCH3); FAB-MS m/ z 481
(M + H)+. Anal. Calcd for C24H24N4O7: C, 60.00; H, 5.03; N,
11.66. Found: C, 60.12; H, 4.99; N, 11.55.
2,3-Bis(ch lor om et h yl)d ih yd r o-2a ,7b -d ip h en yl-6-oxa -
2,3,4,7a-tetr aazacyclopen ta[cd]in den e-1,4-dion e (6b). Com-
pound 6a (1.11 g, 2.31 mmol) was stirred under nitrogen for
16 h in a mixture of 2 mL of CH2Cl2 and 3 mL (41 mmol) of
SOCl2. After addition of 5 mL of diethyl ether, the precipitate
was filtered off, washed with diethyl ether, and dried under
vacuum to yield 0.92 g (92%) of 6b as a white hygroscopic
solid: 1H NMR (CDCl3) δ 7.28-6.92 (m, 10H, ArH), 5.40 and
5.33 (2d, 4H, NCH2Cl, J ) 11.0 Hz), 5.65 and 4.47 (2d, 4H,
NCH2O, J ) 11.1 Hz); FAB-MS m/ z 397 (M - Cl)+. Anal.
Calcd for C20H18N4O3Cl2: C, 55.44; H, 4.19; N, 12.93. Found:
C, 55.58; H, 4.25; N, 12.72.
Mon ow a lled Com p ou n d 7. Meth od A. A stirred sus-
pension of 0.95 g (2.2 mmol) of 6a and 0.30 g (2.2 mmol) of
1,4-dimethoxybenzene in 100 mL of 1,2-dichloroethane was
cooled under nitrogen to -35 °C in an acetone/CO2 bath. SnCl4
(1 mL, 8 mmol) was added, and the mixture was allowed to
warm slowly to 0 °C. A precipitate was formed, which was
filtered at 0 °C, washed with diethyl ether, and redissolved in
100 mL of dichloromethane. The organic layer was washed
with aqueous 1 N HCl and water, dried (MgSO4), and con-
centrated in vacuo to yield 0.96 g (88%) of 7 as a white solid.
Meth od B. A stirred suspension of 1.07 g (2.2 mmol) of 2b
and 0.30 g (2.2 mmol) of 1,4-dimethoxybenzene in 100 mL of
1,2-dichloroethane was cooled under nitrogen to -35 °C in an
acetone/CO2 bath. SnCl4 (1 mL, 8 mmol) was added. The
mixture was allowed to warm slowly to 0 °C, and 10 mL of
aqueous 6 N HCl was added. After the mixture was stirred
15 min, the organic layer was washed with water and
concentrated in vacuo. A mixture of 1, 7, and 3a was obtained
(molar ratio 1:4:1) which could be separated by column
chromatography (CHCl3/MeOH, 197:3, v/v) to yield 0.63 g
(58%) of 7.
It is clear from the binding studies with compounds
15 and 18 that 2,7-DMN side walls give rise to slightly
higher binding constants than 1,4-DMB side walls. This
is also the case for the clips containing a catalytically
active nickel salophene side wall. Compound 25 binds
olivetol with an association constant of Ka ) 920 M-1
,
which is slightly lower than the Ka ) 1200 M-1 measured
for 26. These binding constants are, however, both
higher than those observed for the 1,4-DMN containing
clips 15 and 18. This is probably an effect of the lower
electron density of the nickel salophene functionalized
side wall, which reduces the electrostatic repulsion
between this side wall and the aromatic ring of the bound
guest molecule.
This new synthetic route enables the construction of a
wide variety of novel clip molecules with different side
walls, which can be easily monofunctionalized to give
enzyme mimics. Further detailed binding studies with
these new clip molecules as well as catalytic studies are
reported in separate papers.25,26
Exp er im en ta l Section
Gen er a l. Thionyl chloride and triethylammonium formate
were distilled prior to use. THF and diethyl ether were
distilled under nitrogen from sodium benzophenone ketyl.
Dichloromethane and chloroform were distilled from CaCl2.
1,2-Dichloroethane and methanol were distilled from CaH2.
All other solvents and chemicals were commercial materials
and used as received. Merck silica gel (60H) was used for
column chromatography and Merck silica gel F254 plates for
thin layer chromatography. Melting points were determined
on a J eneval polarization microscope THMS 600 hot stage and
are uncorrected. IR spectra were recorded on a Perkin-Elmer
FTIR 1720-X spectrometer. 1H NMR spectra were recorded
on Bruker WH-90, Bruker AC-100, Bruker WM-200, and
Bruker AM-400 instruments. Chemical shifts are reported in
ppm downfield from internal (CH3)4Si. Abbreviations used are
as follows: s, singlet; d, doublet; m, multiplet; br, broad.
Assignments of proton signals in complicated NMR spectra
were made with the help of 2D COSY techniques. FAB-MS
spectra were recorded on a VG 7070E instrument; the matrix
used was 3-nitrobenzyl alcohol. Field desorption (FD) mass
spectrometry was carried out using a J EOL J MS SX/SX102A
four-sector mass spectrometer, coupled to a J EOL MS-MP7000
data system; 10 µm tungsten wire FD emitters containing car-
bon microneedles with an average length of 30 µm were used.
The samples were dissolved in methanol/water and then
loaded onto the emitters with the dipping technique. An emit-
ter current of 0-15 mA was used to desorb the samples. The
ion source temperature was generally 90 °C. Elemental analy-
ses were determined with a Carbo Erba Ea 1108 instrument.
Com p ou n d s. The syntheses and properties of compounds
1, 2a , 2b, 3a , 3b, 4, 5a ,14 and 16c and 16d 18 have been
Meth od C. To a stirred solution of 1.0 g (2.0 mmol) of 2b
and 1 mL (8 mmol) of SnCl4 in 200 mL of degassed 1,2-
dichloroethane was slowly added (2 mL/min) a solution of 0.28
g (2.0 mmol) of 1,4-dimethoxybenzene in 100 mL of 1,2-
dichloroethane. After the addition of 10 mL of 6 N aqueous
HCl the mixture was stirred for another 15 min. The organic
layer was washed with water and concentrated in vacuo. A
(26) Reek, J . N. H.; Cornelissen, J . J . L. M.; Elemans, J . A. A. W.;
Nolte, R. J . M., manuscript in preparation.
(27) Kraus, G. A.; On Man, T. Synth. Commun. 1986, 16, 1037.

Molecular Clips with Two Different Side Walls
J . Org. Chem., Vol. 62, No. 7, 1997 2241
mixture of 1, 7, and 3a was obtained (molar ratio 1:4:1) which
could be separated by column chromatography as described
under method B to yield 0.52 g (51%) of 7: mp 381 °C dec; 1H
NMR (CDCl3) δ 7.30-7.00 (m, 10H, ArH), 6.83 (s, 2H, ArH),
5.65 and 3.80 (2d, 4H, NCH2Ar, J ) 15.8 Hz), 5.50 and 4.40
(2d, 4H, NCH2O, J ) 11.0 Hz), 3.87 (s, 6H, OCH3); FAB-MS
m/ z 499 (M + H)+. Anal. Calcd for C28H26N4O5: C, 67.46; H,
5.26; N, 11.24. Found: C, 67.63; H, 5.15; N, 11.18.
OCH3); the signals of the amino groups were too broad to be
detected; FAB-MS m/ z 529 (M + H)+. Due to the extreme
instability of the compound, no satisfactory elemental analysis
could be obtained.
Mon ow a lled Com p ou n d 12a . A mixture of 0.43 g (0.73
mmol) of 11a , 50 mg (0.26 mmol) of p-toluenesulfonic acid
monohydrate, and 2 mL of acetic anhydride was stirred at 110
°C for 3 h. After cooling, 8 mL of methanol was added and
the mixture was poured in 100 mL of aqueous 2 N NaOH. The
product was extracted with 2 × 50 mL of CH2Cl2. The
combined organic layers were washed with water, dried
Mon ow a lled Com p ou n d 9. A mixture of 2.0 g (4.1 mmol)
of 2b, 1.0 g (5.3 mmol) of 2,7-dimethoxynaphthalene, and 1.5
mL (12 mmol) of SnCl4 was refluxed under nitrogen for 50 min
in 100 mL of degassed 1,2-dichloroethane. After this period,
10 mL of aqueous 6 N HCl was added, and the mixture was
refluxed for an additional 15 min. After cooling, CH2Cl2 (50
mL) was added, and the organic layer was washed with
aqueous 1 N HCl, aqueous 1 N NaOH (2×), and water and
concentrated in vacuo. Column chromatography (CH2Cl2/
MeOH, 99:1 v/v) gave 1.6 g (71%) of 9 as a white solid: mp
(MgSO4
), and evaporated to dryness to yield 0.48 g (95%) of
12a as a pale yellow solid. The compound was recrystallized
from acetic acid: mp 98-102°C; 1H NMR (CDCl3) δ 7.34-6.82
(m, 10H, ArH), 5.63 and 5.28 (2d, 4H, NCH2
OAc, J ) 11.5 Hz),
5.62 and 3.92 (2d, 4H, NCH2Ar, J ) 16.4 Hz), 4.17 (s, 6H,
OCH3), 2.02 (s, 6H, COCH3); FAB-MS m/ z 631 (M - OAc)+,
713 (M + Na)+
.
Anal. Calcd for C32H30N6O12‚0.5(CH3-
1
COOH): C, 55.00; H, 4.48; N, 11.66. Found: C, 54.88; H, 4.63;
N, 11.63.
315 °C dec; H NMR (CDCl3) see Table 1; FAB-MS m/ z 549
(M + H)+. Anal. Calcd for C32H28N4O5: C, 70.06; H, 5.14; N,
10.21. Found: C, 70.20; H, 5.22; N, 9.99.
Mon ow a lled Com p ou n d 12b. Compound 12a (0.48 g,
0.73 mmol) was stirred under nitrogen for 16 h in a mixture
of 2 mL of CH2Cl2 and 4 mL of SOCl2. The solvent was
removed in vacuo to yield 0.45 g (100%) of 12b as a pale yellow
hygroscopic solid: 1H NMR (CDCl3) δ 7.37-6.83 (m, 10H,
ArH), 5.59 and 3.91 (2d, 4H, NCH2Ar, J ) 16.0 Hz), 5.41 and
5.25 (2d, 4H, NCH2Cl, J ) 11.5 Hz), 4.17 (s, 6H, OCH3); FAB-
MS m/ z 573 (M - 2Cl + H)+. Anal. Calcd for C28H24N6O8-
Cl2: C, 52.27; H, 3.76; N, 13.06. Found: C, 52.47; H, 3.84; N,
12.78.
5,7,12,13b ,13c ,14-H e x a h y d r o -1,4-d ih y d r o x y -8,11-
d im e t h o x y -13b ,13c -d ip h e n y l-6H ,13H -5a ,6a ,12a ,13a -
t et r a a za b en z[5,6]a zu len o[2,1,8-ija ]b en z[f]a zu len e-6,13-
d ion e (13). A suspension of 0.77 g (1.5 mmol) of 7 and 0.61
g (3.2 mmol) of p-toluenesulfonic acid monohydrate in 10 mL
of degassed 1,2-dichloroethane was refluxed under nitrogen
for 10 min over molecular sieves (4 Å). To the resulting clear
solution was added 0.34 g (3.1 mmol) of hydroquinone, and
the mixture was refluxed over molecular sieves for an ad-
ditional 1 h. After cooling, 5 mL of methanol was added, and
the precipitate was collected by filtration and washed with
methanol. After recrystallization from DMSO, 0.67 g (73%)
of 13 was obtained as a white solid: mp 325 °C dec; 1H NMR
(DMSO-d6) δ 8.76 (s, 2H, OH), 7.28-6.90 (m, 10H, ArH), 6.77
and 6.44 (2s, 4H, ArH), 5.37, 5.26, 3.63 and 3.50 (4d, 8H, NCH2-
Ar, J ) 15.8 Hz), 3.69 (s, 6H, OCH3); FAB-MS m/ z 591 (M +
H)+. Anal. Calcd for C34H30N4O6: C, 69.14; H, 5.12; N, 9.49.
Found: C, 69.24; H, 5.19; N, 9.31.
Clip Molecu le 14. Compound 13 (0.13 g, 0.22 mmol) was
dissolved in 5 mL of DMSO. Cu2Cl2 (50 mg) and 0.5 mL of
pyridine were added, and air was bubbled through the mixture
for 2 h. The resulting red suspension was poured into 50 mL
of aqueous 1 N HCl, and the product was extracted with 50
mL of CHCl3. The organic layer was washed with aqueous 1
N HCl, 5% aqueous NH3 (2×), and water (2×) and concen-
trated in vacuo. After purification by column chromatography
(CH2Cl2/MeOH, 98:2 v/v), 0.10 g (77%) of 14 was obtained as
a red solid: mp 312 °C dec; IR 1734, 1714 (CdO), 1655 (CdC);
1H NMR (CDCl3) δ 7.35-6.85 (m, 10H, ArH), 6.72 and 6.65
(2s, 4H, ArH and CH), 5.64, 5.50, 3.77, and 3.67 (4d, 8H, NCH2-
Ar, J ) 15.8 Hz), 3.80 (s, 6H, OCH3); FAB-MS m/ z 591 (M +
4H)+. Anal. Calcd for C34H28N4O6‚(CH2Cl2): C, 62.41; H, 4.49;
N, 8.32. Found: C, 62.29; H, 4.55; N, 8.38.
Clip Molecu le 15. Meth od A. A solution of 0.27 g (0.49
mmol) of 10 and 75 mg (0.54 mmol) of 1,4-dimethoxybenzene
in 1 mL of acetic anhydride and 1 mL of trifluoroacetic acid
was heated for 1 h at 95 °C. After cooling, 4 mL of methanol
was slowly added, and the resulting precipitate was filtered
off, washed with diethyl ether, and dried under vacuum to
yield 106 mg (97%) of 15 as a white solid.
Mon ow a lled Com p ou n d 10. A mixture of 2.4 g (4.9 mmol)
of 2b, 1.1 g (5.9 mmol) of 1,4-dimethoxynaphthalene, and 1.5
mL (12 mmol) of SnCl4 was refluxed under nitrogen for 5 min
in 100 mL of degassed 1,2-dichloroethane. After this period
10 mL of aqueous 6 N HCl was added, and the mixture was
refluxed for an additional 15 min. After cooling, CH2Cl2 (50
mL) was added and the organic layer was washed with
aqueous 1 N HCl, aqueous 1 N NaOH (2×) and water, and
concentrated in vacuo. Column chromatography (CHCl3/
EtOAc, 95:5 v/v) gave 1.1 g (42%) of 10 as a white solid: mp
377 °C dec; 1H NMR (CDCl3) δ 8.10 (m, 2H, Napht H-5,8), 7.53
(m, 2H, Napht H-6,7), 7.27-7.00 (m, 10H, ArH), 5.81 and 4.03
(2d, 4H, NCH2Ar, J ) 15.9 Hz), 5.52 and 4.43 (2d, 4H, NCH2O,
J ) 11.0 Hz), 4.20 (s, 6H, OCH3); FAB-MS m/ z 549 (M + H)+.
Anal. Calcd for C32H28N4O5: C, 70.06; H, 5.14; N, 10.21.
Found: C, 70.08; H, 5.18; N, 10.15.
Mon on itr o Com p ou n d 11a . To an ice-cooled suspension
of 7 (0.49 g, 0.99 mmol) in 2 mL of acetic anhydride was
carefully and slowly added 0.5 mL of aqueous 53% HNO3. The
resulting solution was allowed to warm to room temperature
and stirred for 16 h. A crystalline precipitate was filtered off
and washed with acetic acid and cold ethanol: yield 0.43 g
1
(80%) of 11a as a pale yellow solid; mp 303 °C dec; H NMR
(CDCl3) δ 7.39 (s, 1H, ArH), 7.22-7.03 (m, 10H, ArH), 5.69,
5.65, 3.95 and 3.84 (4d, 4H, NCH2Ar, J ) 15.8 Hz), 5.51 and
4.43 (2 × br d, 4H, NCH2O, J ) 11.0 Hz), 4.10 and 3.96
(2s, 6H, OCH3); FAB-MS m/ z 544 (M + H)+. Anal. Calcd for
C28H25N5O7: C, 61.87; H, 4.64; N, 12.88. Found: C, 62.03; H,
4.67; 12.69.
Din itr o Com p ou n d 11b. To an ice-cooled suspension of
11a (0.35 g, 0.65 mmol) in 2 mL of acetic anhydride was
carefully and slowly added 1 mL of aqueous 53% HNO3. The
resulting solution was allowed to warm to room temperature.
The mixture was stirred for 16 h and then poured into 100
mL of water. The product was extracted with 50 mL of CH2-
Cl2. The organic layer was washed twice with aqueous 1 N
NaOH and with water and concentrated in vacuo. After
purification by column chromatography (CH2Cl2/EtOH, 99:1
v/v), 0.35 g (94%) of 11b was obtained as a pale yellow solid.
The compound was recrystallized from acetic acid: mp 376
°C dec; 1H NMR (CDCl3) δ 7.30-7.00 (m, 10H, ArH), 5.57 and
3.98 (2d, 4H, NCH2Ar, J ) 15.8 Hz), 5.52 and 4.46 (2d, 4H,
NCH2O, J ) 11.0 Hz), 4.19 (s, 6H, OCH3); FAB-MS m/ z 589
(M + H)+. Anal. Calcd for C28H24N6O9‚(CH3COOH): C, 55.54;
H, 4.35; N, 12.96. Found: C, 55.68; H, 4.12; N, 13.05.
Dia m in o Com p ou n d 11c. Compound 11b (0.10 g, 0.17
mmol) was suspended in a degassed mixture of 5 mL of
methanol and 5 mL of THF. Palladium on carbon (25 mg) and
0.5 mL (3.4 mmol) of triethylammonium formate were added.
The mixture was stirred under nitrogen for 16 h and filtered
under nitrogen, and the residue was washed with CH2Cl2 (5
mL). The resulting solution of 11c was used without purifica-
tion for further synthesis. An aliquot of the solution was
evaporated to dryness for analysis: 1H NMR (CDCl3) δ 7.25-
7.04 (m, 10H, ArH), 5.43 and 3.91 (2d, 4H, NCH2Ar, J ) 15.8
Hz), 5.53 and 4.45 (2d, 4H, NCH2O, J ) 11.1 Hz), 3.92 (s, 6H,
Meth od B. A solution of 0.32 g (0.64 mmol) of 7 and 0.24
g (1.29 mmol) of 1,4-dimethoxynaphthalene in 2 mL of acetic
anhydride and 2 mL of trifluoroacetic acid was heated for 3 h
at 95 °C. After cooling, 8 mL of methanol was slowly added,
and the resulting precipitate was filtered off, washed with
diethyl ether, and dried under vacuum to yield 0.30 g (70%)
of 15: mp 263 °C dec; 1H NMR (CDCl3) δ 8.05 (m, 2H, Napht

2242 J . Org. Chem., Vol. 62, No. 7, 1997
Reek et al.
H-5,8), 7.48 (m, 2H, Napht H-6,7), 7.35-6.95 (m, 10H, ArH),
6.67 (s, 2H, ArH), 5.73, 5.59, 3.94, and 3.79 (4d, 8H, NCH2Ar,
J ) 16.0 Hz), 4.08 and 3.76 (2s, 12H, OCH3); FAB-MS m/ z
669 (M + H)+. Anal. Calcd for C40H36N4O6: C, 71.84; H, 5.43;
N, 8.38. Found: C, 72.07; H, 5.36; N, 8.21.
ArH, J ) 7.3 Hz), 6.28 (t, 1H, ArH, J ) 7.3 Hz), 6.16 and 4.98
(2d, 4H, NCH2Napht, J ) 14.5 Hz), 5.46 and 3.80 (2d, 4H,
NCH2Ph, J ) 15.9 Hz), 4.01 and 3.96 (2s, 12H, OCH3); anti-
conformer (30%) δ 7.30-6.80 (m, 10H, ArH), 7.65 and 7.16 (2d,
4H, NCH2Napht, J ) 9.0 Hz), 5.97 and 4.19 (2d, 4H, NCH2-
Napht, J ) 16.1 Hz), 5.38 and 3.72 (2d, 4H, NCH2Ph, J ) 16.1
Hz), 4.05 and 3.69 (2s, 12H, OCH3); the signals of the amino
protons were too broad to be detected; FAB-MS m/ z 699 (M
+ H)+. Due to the extreme instability of this compound, no
satisfactory elemental analysis could be obtained, and the
compound was immediately used for further reaction.
Com p ou n d 18. With 9 (0.20 g, 0.36 mmol) and 1,4-
dimethoxynaphthalene (0.14 g, 0.72 mmol) as starting materi-
als, this compound was synthesized as described for 15
(method B) to yield 0.17 g (65%) of 18 as a white solid: mp
322 °C dec; IR 1711 (CdO); 1H NMR (CDCl3) see Table 1; FAB-
MS m/ z 719 (M + H)+. Anal. Calcd for C44H38N4O6: C, 73.52;
H, 5.33; N, 7.79. Found: C, 73.87; H, 5.29; N, 7.72.
5,7,12,13b,13c,14-Hexa h yd r o-1,4,8,11-tetr a m eth oxy-2,3-
d in it r o-13b ,13c-d ip h e n yl-6H ,13H -5a ,6a ,12a ,13a -t e t r a -
a za b e n z[5,6]a zu le n o[2,1,8-ija ]b e n z[f]a zu le n e -6,13-d i-
on e (16a ). With 11b (0.35 g, 0.60 mmol) and 1,4-dimethoxy-
benzene (90 mg, 0.65 mmol) as starting materials, this
compound was synthesized as described for 15 (method A) to
yield 0.40 g (96%) of 16a as a pale yellow solid. The compound
was recrystallized from acetic acid: IR 1708 (CdO), 1546, 1358
1
(N-O); H NMR (CDCl3) δ 7.30-6.95 (m, 10H, ArH), 6.85 (s,
2H, ArH), 5.61 and 3.80 (2d, 4H, NCH2Ar, J ) 15.9 Hz), 5.52
and 3.88 (2d, 4H, NCH2Ar, J ) 16.4 Hz), 4.07 and 3.82
(2s, 12H, OCH3); FAB-MS m/ z 709 (M + H)+. Anal. Calcd
for C36H32N6O10‚(CH3COOH): C, 59.36; H, 4.72; N, 10.94.
Found: C, 59.61; H, 4.59; N, 10.82.
Mon ow a lled P h en a n th r olin e Com p ou n d 19. Com-
pound 11b (90 mg, 0.15 mmol) was reduced to 11c as described
above. To a solution of 11c in a mixture of 5 mL of methanol,
5 mL of THF, and 5 mL of CH2Cl2 was added 56 mg (0.27
mmol) of 1,10-phenanthroline-5,6-quinone. The mixture was
refluxed under nitrogen for 16 h, the condensed solvent
running back over molecular sieves (3 Å). CH2Cl2 was added
(25 mL), and the organic layer was washed with aqueous 1 N
NaOH, water, and concentrated in vacuo. After purification
by column chromatography (CH2Cl2/EtOH, 93:7 v/v), 84 mg
(78%, based on 11b) of 19 could be obtained as a yellow solid:
5,7,12,13b,13c,14-Hexa h yd r o-1,4,8,11-tetr a m eth oxy-2,3-
d ia m in o-13b ,13c-d ip h en yl-6H ,13H -5a ,6a ,12a ,13a -t et r a -
a za b e n z[5,6]a zu le n o[2,1,8-ija ]b e n z[f]a zu le n e -6,13-d i-
on e (16b). Compound 16a (0.21 g, 0.30 mmol) was suspended
in a degassed mixture of 10 mL of methanol and 10 mL of
THF. Palladium on carbon (50 mg) and 1 mL (7 mmol) of
triethylammonium formate were added. The mixture was
stirred under nitrogen for 16 h and filtered under nitrogen,
and the residue was washed with CH2Cl2 (10 mL). The
resulting solution of 16b was used without purification for
further synthesis. An aliquot of the solution was evaporated
to dryness for analysis: mp 311 °C dec; 1H NMR (CDCl3) δ
7.18-6.92 (m, 10H, ArH), 6.71 (s, 2H, ArH), 5.60, 5.36, 3.83,
and 3.78 (4d, 8H, NCH2Ar, J ) 15.8 Hz), 5.0-4.0 (br s, 4H,
NH2), 3.82 and 3.77 (2s, 12H, OCH3); FAB-MS m/ z 649 (M +
H)+. Due to the extreme instability of the compound, no
satisfactory elemental analysis could be obtained.
Clip Molecu le 17a . With 9 (0.38 g, 0.69 mmol) and 1,4-
dimethoxybenzene (0.11 g, 0.80 mmol) as starting materials,
this compound was synthesized as described for 15 (method
A) to yield 0.43 g (93%) of 17a as a white solid: mp 317 °C
dec; IR 1727, 1712 (CdO); 1H NMR (CDCl3) see Table 1; FAB-
MS m/ z 669 (M + H)+. Anal. Calcd for C40H36N4O6: C, 71.84;
H, 5.43; N, 8.38. Found: C, 71.85; H, 5.43; N, 8.37.
Din itr o Com p ou n d 17b. To a solution of 0.45 g (0.70
mmol) of 12b and 0.26 g (1.4 mmol) of 2,7-dimethoxynaph-
thalene in 40 mL of degassed 1,2-dichloroethane was added 1
mL (8 mmol) of SnCl4. The mixture was refluxed under
nitrogen for 3 h. After cooling, 4 mL of aqueous 6 N HCl was
added, and the mixture was refluxed for another 30 min. After
cooling, 100 mL of aqueous 1 N HCl was added, and the
product was extracted with 2 × 50 mL of CH2Cl2. The
combined organic layers were washed with aqueous 1 N NaOH
and with water. After evaporation of the solvent, the product
was purified by column chromatography (CH2Cl2/MeOH, 199:1
v/v) to yield 0.32 g (60%) of 17b as a pale yellow solid. The
compound was recrystallized from acetic acid: mp 265 °C; 1H
NMR (CDCl3) syn-conformer (65%) δ 7.29 and 6.95 (2d, 4H,
NaphtH, J ) 9.1 Hz), 7.20-6.95 (m, 5H, ArH), 6.45 and 6.18
(2d, 4H, ArH, J ) 7.0 Hz), 6.28 (t, 1H, ArH, J ) 7.0 Hz), 6.15
and 5.00 (2d, 4H, NCH2Napht, J ) 14.5 Hz), 5.60 and 3.87
(2d, 4H, NCH2Ph, J ) 16.4 Hz), 4.27 and 3.98 (2s, 12H, OCH3);
anti-conformer (35%) δ 7.69 and 7.16 (2d, 4H, NaphtH, J )
9.1 Hz), 7.20-6.95 (m, 10H, ArH), 5.93 and 4.11 (2d, 4H, NCH2-
Napht, J ) 16.4 Hz), 5.41 and 3.78 (2d, 4H, NCH2Ph, J ) 16.4
Hz), 4.04 and 3.89 (2s, 12H, OCH3); FAB-MS m/ z 759 (M +
H)+. Anal. Calcd for C40H34N6O10‚(CH3COOH): C, 61.61; H,
4.68; N, 10.26. Found: C, 61.71; H, 4.64; N, 10.20.
Dia m in o Com p ou n d 17c. Compound 17b (0.26 g, 0.34
mmol) was suspended in a degassed mixture of 10 mL of THF
and 10 mL of methanol. Palladium on carbon (200 mg) and 1
mL (6.8 mmol) of triethylammonium formate were added. The
mixture was stirred under nitrogen for 24 h and filtered under
nitrogen, and the residue was washed with 10 mL of CH2Cl2.
The filtrate was evaporated to dryness to yield 0.24 g (100%)
of 17c as a pale yellow very hygroscopic solid: 1H NMR
(CDCl3) syn-conformer (70%) δ 7.30-6.80 (m, 5H, ArH), 7.10
and 6.88 (2d, 4H, NaphtH, J ) 9.0 Hz), 6.45 and 6.18 (2d, 4H,
1
mp > 400 °C; H NMR (CDCl3) δ 9.60 (dd, 2H, PhenH, J )
8.0 Hz, J ) 2.0 Hz), 9.27 (dd, 2H, PhenH, J ) 4.7 Hz, J ) 2.0
Hz), 7.81 (dd, 2H, PhenH, J ) 8.0 Hz, J ) 4.7 Hz), 7.36-7.03
(m, 10H, ArH), 6.03 and 4.09 (2d, 4H, NCH2Ar, J ) 15.8 Hz),
5.53 and 4.45 (2d, 4H, NCH2O, J ) 11.3 Hz), 4.64 (s, 6H,
OCH3); FAB-MS m/ z 703 (M + H)+. Anal. Calcd for C40H30
-
N8O5‚(C2H6O): C, 66.14; H, 4.46; N, 14.70. Found: C, 66.39;
H, 4.64; N, 14.57.
Dip h en a n th r olin e Clip 20. Compound 16c (0.53 g, 0.66
mmol) was reduced to 16d as described above. To a solution
of 16d in a mixture of 20 mL of methanol, 20 mL of THF, and
20 mL of CH2Cl2 was added 0.33 g (1.6 mmol) of 1,10-
phenanthroline-5,6-quinone. The mixture was refluxed under
nitrogen for 16 h, the condensed solvent running back over
molecular sieves (3 Å). CH2Cl2 was added (100 mL), and the
organic layer was washed with aqueous 1 N NaOH and water
and concentrated in vacuo. After purification by column
chromatography (CHCl3/MeOH, 9:1 v/v), 0.45 g (66% based on
1
16c) of 20 was obtained as a yellow solid: mp > 400 °C; H
NMR (CDCl3) δ 9.29 (dd, 4H, PhenH, J ) 8.2 Hz, J ) 2.0 Hz),
9.08 (dd, 4H, PhenH, J ) 4.5 Hz, J ) 2.0 Hz), 7.52 (dd, 4H,
PhenH, J ) 8.2 Hz, J ) 4.5 Hz), 7.45-7.11 (m, 10H, ArH),
6.03 and 4.05 (2d, 8H, NCH2Ar, J ) 16.0 Hz), 4.47 (s, 12H,
OCH3); FAB-MS m/ z 1027 (M + H)+. Anal. Calcd for C60H42
-
N12O6‚CHCl3: C, 63.91; H, 3.78; N, 14.66. Found: C, 63.81;
H, 3.92; N, 14.62.
Mon op h en a n th r olin e Clip 21. Compound 16a (0.56 g,
0.79 mmol) was reduced to 16b as described above. To a
solution of 16b in a mixture of 20 mL of methanol, 20 mL of
THF, and 20 mL of CH2Cl2 was added 0.25 g (1.2 mmol) of
1,10-phenanthroline-5,6-quinone. The mixture was refluxed
under nitrogen for 16 h, the condensed solvent running back
over molecular sieves (3 Å). CH2Cl2 was added (100 mL), and
the organic layer was washed with aqueous 1 N NaOH and
water, and concentrated in vacuo. After purification by column
chromatography (CH2Cl2/EtOH, 93:7, v/v), 0.49 g (75% based
on 16a ) of 21 was obtained as a yellow solid: mp 392 °C dec;
IR 1714 (CdO); 1H NMR (CDCl3) δ 9.49 (dd, 2H, PhenH, J )
7.9 Hz, J ) 2.0 Hz), 9.20 (dd, 2H, PhenH, J ) 7.9 Hz, J ) 4.6
Hz), 7.65 (dd, J ) 7.9 Hz, J ) 4.6 Hz), 7.32-7.08 (m, 10H,
ArH), 6.57 (s, 2H, ArH), 5.99, 5.62, 4.02 and 3.84 (4d, 8H,
NCH2Ar, J ) 15.8 Hz), 4.55 and 3.72 (2s, 12H, OCH3); FAB-
MS m/ z 823 (M + H)+. Anal. Calcd for C48H38N8O6‚CH2Cl2:
C, 64.34; H, 4.44; N, 12.34. Found: C, 64.96; H, 4.47; N, 12.18.
Mon od ip yr id in e Clip 22. Compound 16a (0.19 g, 0.27
mmol) was reduced to 16b as described above. To a solution
of 16b in a mixture of 10 mL of methanol, 10 mL of THF, and
10 mL of CH2Cl2 was added 0.11 g (0.89 mmol) of 2,2′-pyridil.

Molecular Clips with Two Different Side Walls
J . Org. Chem., Vol. 62, No. 7, 1997 2243
The mixture was refluxed under nitrogen for 16 h, the
condensed solvent running back over molecular sieves (3 Å).
CH2Cl2 was added (50 mL), and the organic layer was washed
with aqueous 1 N NaOH and water and concentrated in vacuo.
After purification by column chromatography (CHCl3/MeOH,
197:3 v/v), 69 mg (31% based on 16a ) of 22 was obtained as a
yellow solid: mp 365 °C dec; 1H NMR (CDCl3) δ 8.28-8.05
(m, 4H, PyH), 7.91-7.75 (m, 2H, PyH), 7.45-6.95 (m, 12H,
PyH and ArH), 6.65 (s, 2H, ArH), 5.88, 5.56, 3.96 and 3.80
(4d, 8H, NCH2Ar, J ) 15.8 Hz), 4.34 and 3.75 (2s, 12H, OCH3);
FAB-MS m/ z 825 (M + H)+. Anal. Calcd for C48H40N8O6: C,
69.89; H, 4.89; N, 13.58. Found: C, 70.14; H, 4.97; N, 13.24.
Mon op or p h yr in Clip 23a . Compound 16a (0.18 g, 0.25
mmol) was reduced to 16b as described above. The methanol
and the THF was evaporated in vacuo. To a solution of 16b
in 10 mL of CH2Cl2 was added 0.10 g (0.16 mmol) of 24a . The
mixture was refluxed under nitrogen for 16 h over molecular
sieves (3 Å). CH2Cl2 was added (50 mL), and the organic layer
was washed with aqueous 1 N NaOH and water and concen-
trated in vacuo. After purification by column chromatography
(CH2Cl2), 180 mg (92% based on 24a ) of 23a was obtained as
h. The solvent was removed in vacuo, and the residue was
suspended in 150 mL of methanol. After filtration, the residue
was redissolved in 100 mL of CHCl3. The organic layer was
washed with water (3×), dried (MgSO4), and concentrated in
vacuo to yield 0.40 g (66%) of 25 as a red solid. A sample was
recrystallized by slow diffusion of n-hexane in a solution of 25
in CHCl3: mp 382 °C dec; 1H NMR (CDCl3) δ 9.15 (s, 2H,
NCHAr), 7.32-7.03 (m, 16H, ArH), 6.70 (s, 2H, ArH), 6.62 (t,
2H, ArH, J ) 7.6 Hz), 5.62, 5.57, 3.86 and 3.77 (4d, 8H, NCH2-
Ar, J ) 15.8 Hz), 3.79 and 3.68 (2s, 12H, OCH3); FAB-MS m/ z
913 (M + H)+. Anal. Calcd for C50H42N6O8Ni‚(CHCl3): C,
59.30; H, 4.20; N, 8.14. Found: C, 59.33; H, 4.29; N, 8.01.
Nick el Sa lop h en Com p ou n d 26. To a solution of com-
pound 17c (0.24 g, 0.34 mmol) in a mixture of 10 mL of THF
and 10 mL of methanol were added 125 mg (1.02 mmol) of
2-hydroxybenzaldehyde and a solution of 127 mg (0.51 mmol)
of Ni(OAc)2‚4H20 in 1 mL of methanol. The mixture was
stirred under nitrogen for 64 h. The solvent was removed in
vacuo, and the residue was suspended in 75 mL of methanol.
After filtration, the residue was redissolved in 50 mL of CHCl3.
The organic layer was washed with water (3×), dried (MgSO4)
and concentrated in vacuo to yield 0.10 g (31%) of 26 as a red
solid: mp 373 °C dec; 1H NMR see Table 2; FAB-MS m/ z 963
(M + H)+; HRMS (field desorption) calculated for C54H44N6O8-
Ni 962.257, found 962.253.
1
a purple solid: mp 262 °C dec; H NMR (CDCl3) δ 8.85 and
8.69 (2d, 4H, â pyrrole, J ) 5.0 Hz), 8.68 (s, 2H, â pyrrole),
8.21 (m, 8H, Ar H-2,6 porphyrin), 7.84 (m, 8H, Ar H-3,5
porphyrin), 7.76 (m, 4H, Ar H-4 Porphyrin), 7.15 and 7.12 (2s,
10H, ArH), 6.62 (s, 2H, ArH), 5.90, 5.57, 3.89 and 3.80 (4d,
8H, NCH2Ar, J ) 15.8 Hz), 3.86 and 3.75 (2s, 12H, OCH3),
-2.53 (br s, 2H, NH); FAB-MS m/ z 1257 (M + H)+. Anal.
Calcd for C80H60N10O6: C, 76.42; H, 4.81; N, 11.14. Found:
C, 76.72; H, 4.95; N, 10.78.
Mon op h en a n th r olin e Com p ou n d 27. To a solution of
0.11 g (0.16 mmol) of 17c in a mixture of 7 mL of THF and 7
mL of methanol was added 60 mg (0.29 mmol) of 1,10-
phenathroline-5,6-quinone. The mixture was refluxed under
nitrogen for 64 h over molecular sieves (3 Å). After cooling,
the precipitate was filtered off and washed with diethyl ether.
The product was purified by column chromatography (CH2-
Cl2/MeOH, 93:7 v/v) to yield 0.11 g (80%) of 27 as a yellow
Mon op or p h yr in Clip 23b. This molecule was synthesized
in an analogous manner to 23a using 24b instead of 24a : 1H
NMR (CDCl3) δ 8.91 and 8.54 (2d, 4 H, J ) 5.0 Hz, â pyrrolic
H), 8.65 (s, 2 H, â pyrrolic H), 8.12 (s, 2 H, ArH porphyrin),
8.08 (s, 2 H, ArH porphyrin), 8.01 (s, 2 H, ArH porphyrin),
7.86 (s, 2 H, ArH porphyrin), 7.85 (s, 2 H, ArH porphyrin),
7.77 (s, 2 H, ArH porphyrin), 7.10 (m, 10 H, ArH diphenylg-
lycoluril), 6.46 (s, 2 H, ArH), 5.90 and 3.93 (2d, 4 H, J ) 15.8
Hz, NCHHAr), 5.44 and 3.69 (2d, 4 H, J ) 15.8 Hz, NCH2Ar)
3.73 (s, 6 H, OCH3) 3.62 (s, 6 H, OCH3), 1.52, 1.50, 1.41, and
1.26 (4s, 72 H, CCH3), -2.50 (br s, 2H, NH); FAB-MS m/ z
1706 (M)+. Anal. Calcd for C112H124N10O6: C, 78.84; H, 7.32;
N, 8.21. Found: C, 78.99; H, 7.36; N, 8.02.
1
solid: mp >400 °C; H NMR see Table 2; FAB-MS m/ z 873
(M + H).+ Anal. Calcd for C52H40N6O8‚(CH2Cl2): C, 66.46; H,
4.42; N, 11.70. Found: C, 66.45; H, 4.45; N, 11.34.
Mon op or p h yr in Com p ou n d 28. To a solution of 0.10 g
(0.15 mmol) of 17c in 7 mL of CH2Cl2 was added 250 mg of
24b (0.27 mmol). The mixture was refluxed over molecular
sieves (3 Å) under nitrogen for 48 h. After cooling, the solvent
was evaporated, and the product was purified by column
chromatography (CH2Cl2) to yield 70 mg (26%) of 28 as a
purple solid: mp >400 °C; 1H NMR see Table 2; FAB-MS m/ z
1760 (M + 4H)+. Anal. Calcd for C116H128N10O6: C, 79.24; H,
7.34; N, 7.97. Found: C, 79.02; H, 7.57; N, 8.11.
Nick el Sa lop h en Com p ou n d 25. To a solution of 0.43 g
(0.66 mmol) of 16b in a mixture of 20 mL of THF and 20 mL
of methanol were added 0.24 g (1.97 mmol) of 2-hydroxyben-
zaldehyde and a solution of 0.25 g of Ni(OAc)2‚4H2O in 2 mL
of methanol. The mixture was stirred under nitrogen for 64
J O961382N