Quantitative Evaluation of Template Effect in the Formation of Cyclobis(paraquat-p-phenylene)

Full text of DOI:10.1021/jo970702f

J . Org. Chem. 1997, 62, 7015-7017
7015
Notes
ethoxy]benzene (3).6 It was suggested that the reaction
occurs in two steps, as shown in Scheme 1, and that only
the second one, i.e., the ring closure reaction of the
intermediate 5, benefits from the template ability of the
guest.7 However compound 5 has never been observed.
Recently, complexes containing a similar tricationic
intermediate, bound to two different macrocyclic poly-
ethers, have been detected by FAB mass spectrometry.4
In order to evaluate the template effect of the guest 3
on the formation of the cyclophane 4, the synthesis of 5
is required. The preparation of 5 was carried out
according to the route illustrated in Scheme 2. Equimo-
lar amounts of the compound 6 and the salt 1 were
allowed to react in acetonitrile at room temperature for
24 h affording, after column chromatography, the tricat-
ionic ester salt 7‚3PF6 in 14% yield. This low yield was
reproducible. The ester 7‚3PF6 was converted to the
hydrobromide of 5 by treatment with 48% HBr, at 85 °C
for 2 days and was isolated as 5H‚4PF6 in 78% yield.
Deprotonation of 5H‚4Br in water afforded the trication
5 which was then precipitated as 5‚3PF6 in 89% yield.
The kinetics of cyclization of 5‚3PF6 was studied by
both 1H NMR spectroscopy in CD3CN, by following the
disappearance of the CH2Br signal, and UV-vis spec-
troscopy in acetonitrile, by following the appearance of
the charge-transfer band at λ 467 nm of the complex
formed between 3 and 4.6 To avoid polymerization
reactions the concentration of 5 was kept as low as
possible (3-5 × 10-3 M in the 1H NMR experiments, 6-7
× 10-4 M in the UV-vis experiments). The kinetic
measurements were carried out at 62 °C, since a pre-
liminary kinetic investigation showed that the ring
closure reaction is very slow at room temperature. First-
order rate constants were obtained in the absence (k0)
and in the presence (kobs) of variable excess amounts of
guest 3.8 The ratios kobs/k0 (see Experimental Section),
plotted in Figure 1 against the guest concentration,
provide a measure of the extent of catalysis produced by
the presence of the template.
Qu a n tita tive Eva lu a tion of Tem p la te Effect
in th e F or m a tion of
Cyclobis(p a r a qu a t-p-p h en ylen e)
Sabrina Capobianchi,† Giancarlo Doddi,*,†
Gianfranco Ercolani,*,‡ J ohn W. Keyes,† and
Paolo Mencarelli*,†
Dipartimento di Chimica e Centro CNR di Studio sui
Meccanismi di Reazione, Universita` di Roma La Sapienza,
P.le Aldo Moro, 2, 00185 Roma, Italy, Dipartimento di
Scienze e Tecnologie Chimiche, Universita` di Roma Tor
Vergata, Via della Ricerca Scientifica, 00133 Roma, Italy
Received April 21, 1997
In the last decade there has been an increasing use of
templates in synthesis which has enormously contributed
to the development of supramolecular chemistry.1
Macrocyclization templates are the most exploited;
they range from simple metal cations to structured
organic guests. Countless examples of this type are
found in literature; however the reported evidences are
generally based on yield increases only.2 A notable
exception is due to Mandolini’s group that carried out a
thorough kinetic investigation on the template effect of
alkali and alkaline-earth cations in the formation of
benzo-crown ethers.3 However in the case of template
effects brought about by organic guests no kinetic study
has been reported to date. This is due to the great
difficulty in having a clean reaction in which macrocy-
clization is the only process, or at least the principal one.
This in turn would require the, often not easy, prepara-
tion of the acyclic intermediate immediately preceding
the macrocycle along the reaction path.
By using a different approach based on competitive
experiments Stoddart et al. have recently assessed the
relative template abilities of two different crown ethers
in the formation of [2]catenanes.4
Among the literature examples of macrocycles whose
formation is catalyzed by the presence of an organic
molecule, no doubt, the most versatile system is cyclo-
bis(paraquat-p-phenylene) (4), which has inspired most
of the recent work of Stoddart and co-workers.5 They
reported, inter alia, that the yield of 4 is significantly
increased by the presence of 1,4-bis[2-(2-hydroxyethoxy)-
It has long been recognized that catalysis is observed
when the catalyst binds the transition state more strongly
than the reactants.9 The results here reported can be
easily rationalized by eq 1 which is obtained from the
#
distribution scheme in Figure 2, where Ksub and KT are
the association constants of the guest with the substrate
and with the transition state, respectively.3
† Universita` di Roma La Sapienza.
#
‡ Universita` di Roma Tor Vergata.
kobs/k0 ) (1 + KT [guest])/(1 + Ksub[guest]) (1)
(1) (a) Stoddart, J . F. In Frontiers in Supramolecular Organic
Chemistry and Photochemistry; Schneider, H.-J .; Du¨rr, H., Eds.;
VCH: Weinheim, 1991; pp 251-263. (b) Anderson, S.; Anderson, H.
L.; Sanders, J . K. M. Acc. Chem. Res. 1993, 26, 469. (c) Hoss, R.; Vo¨gtle,
F. Angew. Chem., Int. Ed. Engl. 1994, 33, 375. (d) Busch, D. H.; Vance,
A. L.; Kolchinski, A. G. In Comprehensive Supramolecular Chemistry,
Vol. 9; Atwood, J . L., Davies, J . E. D., MacNicol, D. D., Vo¨gtle, F., Eds.;
Pergamon: Oxford, 1996; Chapter 1.
Nonlinear least squares fit to eq 1 of the kobs/k0 ratios
obtained by NMR and UV-vis, respectively, provided two
(6) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado,
M.; Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietrasz-
kiewicz, M.; Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer,
N.; Stoddart, J . F.; Vicent, C.; Williams, D. J . J . Am. Chem. Soc. 1992,
114, 193.
(2) For an attempt to translate yield increases into rate factors,
see: Anderson, S.; Anderson, H. L.; Sanders, J . K. M. J . Chem. Soc.,
Perkin Trans. 1 1995, 2255.
(3) (a) Mandolini, L. Pure Appl. Chem. 1986, 58, 1485. (b) Cacciapa-
glia, R.; Mandolini, L. Chem. Soc. Rev. 1993, 22, 221.
(4) Amabilino, D. B.; Ashton, P. R.; Perez-Garc´ıa, L.; Stoddart, J .
F. Angew. Chem., Int. Ed. Engl. 1995, 34, 2378.
(5) (a) Amabilino, D. B.; Stoddart, J . F. Chem. Rev. 1995, 95, 2725.
(b) Philp, D.; Stoddart, J . F. Angew. Chem., Int. Ed. Engl. 1996, 35,
1154.
(7) Brown, C. L.; Philp, D.; Spencer, N.; Stoddart, J . F. Isr. J . Chem.
1992, 32, 61.
(8) (a) It is not possible to evaluate k0 by UV-vis spectroscopy
because in the absence of 3, of course, the charge-transfer band is
absent. (b) The upper limit of the concentration of 3 was imposed by
its solubility in acetonitrile.
(9) Kraut, J . Science 1988, 242, 533 and references therein.
S0022-3263(97)00702-0 CCC: $14.00 © 1997 American Chemical Society

7016 J . Org. Chem., Vol. 62, No. 20, 1997
Notes
Sch em e 1
Sch em e 2
F igu r e 1. Catalytic effects of guest 3 on the ring closure of 5
1
as measured by H NMR (b) and UV-vis (4) techniques. The
points are experimental and the curves are calculated.
sets of association constants. By the NMR data we
obtained KT ) 140 ( 17 M-1 and Ksub ≈ 0 M-1, by the
#
UV-vis data we obtained KT ) 144 ( 7 M-1 and Ksub
)
#
1.9 ( 0.5 M-1
. The two sets of constants are quite
consistent; however the UV-vis data should be held as
more reliable because of the lower substrate concentra-
tion, the better temperature control, and the inherent
greater sensitivity and accuracy of the UV-vis technique.
Interestingly the plot in Figure 1 obtained by the UV-
vis technique shows an undeniable tendency to satura-
tion which is absent in the NMR plot. The saturation
F igu r e 2. Distribution scheme, derived from transition state
theory, considering the association equilibria of the guest 3
with the substrate 5 and with the transition state.
#
value KT /Ksub is the maximum theoretical catalytic effect
which would be attained when the host is completely
bound to the guest.3 This value indicates that the
complexed form of 5 is 76((24) times more reactive than
the free one.
Overall, these results indicate that, while the acyclic
precursor 5 does not appreciably associate, the cyclic
transition state shows a significant ligand affinity toward
the guest 3. This is mainly due to the preorganization
of the cyclic transition state and, secondarily, to the
developing positive charge on the nucleophilic nitrogen.
One may note that the association constant of the
transition state is more than 1 order of magnitude lower
than that of the reaction product 4 (2220 M-1 at 25 °C).6
The major factors responsible for this behavior should
be searched among the different structural features of
the transition state and the cyclophane 4. Although the
interactions between the guest and the transition state
should be of the same nature of those existing between
the guest and the host 4,6,10 the transition state differs
(10) Asakawa, M.; Dehaen, W.; L’abbe´, G.; Menzer, S.; Nouwen, J .;
Raymo, F. M.; Stoddart, J . F.; Williams, D. J . J . Org. Chem. 1996, 61,
9591 and references therein.

Notes
J . Org. Chem., Vol. 62, No. 20, 1997 7017
aqueous solution of NH4PF6 was added until no further precipi-
tation was observed. After filtration 7‚3PF6 was obtained as a
white solid (0.414 g, yield 14%, g95% pure by 1H NMR): 1H
NMR (CD3CN) δ 2.06 (3H, s), 5.11 (2H, s), 5.82-5.85 (6H, m),
7.50 (4H, s), 7.60 (4H, s), 8.01-8.04 (2H, m), 8.36-8.40 (6H, m),
8.87-8.98 (8H, m); ES-MS m/ z 870 (M - PF6)+.
from the cyclophane 4 in two respects: (i) the nucleophilic
nitrogen should bear only a partial positive charge
against the net charge in 4; (ii) the cavity should be less
tight and more irregular than that of 4 since the N-C
bond is not completely formed. Both these features would
weaken the ligand affinity of the transition state with
respect to 4.
It should be noted that the availability of the trication
5 opens up new fronts regarding the study of template
effects in the formation of more exotic systems such as
the rotaxanes and catenanes already synthesized by
Stoddart and co-workers.5,6
1,1′′-[1,4-P h en ylen eb is(m et h ylen e)]-1′-(4-(b r om om et h -
yl)b en zyl)-b is(4,4′-b ip yr id in iu m ) Tr is(h exa flu or op h os-
p h a te) (5‚3P F 6). The salt 7‚3PF6 (0.414 g, 0.408 mmol) in 30
mL of 48% HBr was heated at 85 °C, for 2 days. The reaction
mixture was diluted to 100 mL with water, and a saturated
aqueous solution of NH4PF6 was added until no further precipi-
tation of 5H‚4PF6 was observed (0.373 g, yield 78%). 5H‚4PF6
was then converted to 5H‚4Br by anion exchange11 with Et4NBr
in MeNO2. 5H‚4Br was dissolved in 100 mL of water and
deprotonated by adjusting the pH to 6 with 0.2 N NaOH, and
then precipitated as 5‚3PF6 (0.291 g, yield 89%, g95% pure by
1H NMR). A TLC analysis (silica gel, CH3OH/CH3NO2/2 N
aqueous NH4Cl solution 7:2:1) of 5‚3PF6 confirmed the absence
of other products: 1H NMR (CD3CN) δ 4.61 (2H, s), 5.80-5.86
(6H, m), 7.47-7.60 (8H, m), 7.91-7.93 (2H, m), 8.34-8.40 (6H,
m), 8.85-8.98 (8H, m); ES-MS m/ z 890 (M - PF6)+.
Exp er im en ta l Section
Gen er a l a n d In str u m en ta tion . Thin-layer chromatogra-
phies (TLC) were carried out on 5 × 20 plates coated with silica
gel 60 F254 (Merck 1.05714). Column chromatographies were
performed on silica gel 60 70-230 mesh (Merck 1.07734). 1H
NMR spectra were recorded at 300 MHz on a Bruker AC 300
instrument. ES mass spectra were obtained on a Fison Instru-
ments VG-Platform benchtop mass spectrometer. The spectro-
photometric measurements were carried out on a Varian Cary1
instrument.
Kin etic Mea su r em en ts. The 1H NMR kinetic measure-
ments were carried out as follows. A 5 mm NMR tube containing
a CD3CN solution of 5‚3PF6 and the guest 3 in the appropriate
concentrations was kept in a thermostatic bath at 62 °C. At
regular intervals an 1H NMR spectrum was recorded at room
temperature. The integral of the CH2Br signal was taken
relatively to an internal standard (1,3,5-tri-tert-butylbenzene).
The spectrophotometric kinetic measurements were carried
out, at 62 °C, in acetonitrile (Carlo Erba, HPLC grade), in a 3
mL cuvette (optical path 1 cm) kept in the thermostatted cell
compartment of a Varian Cary1 instrument. In a typical run,
100 µL of a solution 0.0193 M of 5‚3PF6 were added to a 2.5 mL
solution of 3 at the appropriate concentration (see below). The
appearance of the charge-transfer band of the complex formed
between 3 and 4 was followed at λ 467 nm. In all of the cases
first-order behavior was observed. Relative kinetic constants
(kobs/k0, where k0 ) 8.3 × 10-7 s-1) at the various guest
concentrations, corrected for the volume increase at 62 °C, given
in parentheses in M were as follows:
4-(Br om om eth yl)ben zyl a ceta te (6) was prepared by react-
ing 1,4-bis(bromomethyl)benzene (10.5 g, 39.8 mmol) with 1
equiv of potassium acetate in 100 mL of DMF (Fluka puriss.
over molecular sieve) at 80 °C for 22 h. The solvent was removed
in vacuo and the solid extracted with ethyl ether (4 × 50 mL).
The four fractions were combined and dried (Na2SO4), and the
solvent was removed in vacuo. Column chromatography (silica
gel, benzene) afforded 6 (3.76 g, 39% yield) as a white solid
1
(g95% pure by H NMR). Since 6 slowly decomposes (in about
a month) on standing at room temperature, it must be stored
under argon at -20 °C: 1H NMR (CDCl3) δ 2.11 (3H, s), 4.49
(2H, s), 5.10 (2H, s), 7.37 (4H, m); ES-MS m/ z 266 (M + Na)+.
1,1′′-[1,4-P h en ylen ebis(m eth ylen e)]-1′-(4-(a cetoxym eth -
yl)b en zyl)-b is(4,4′-b ip yr id in iu m ) Tr is(h exa flu or op h os-
p h a te) (7‚3P F 6). The tricationic ester 7 was prepared by adding
dropwise, to a 20 mL solution of 1‚2PF6 (2.00 g, 2.83 mmol) in
acetonitrile (Carlo Erba, HPLC grade), 15 mL of an acetonitrile
solution containing 6 (0.688 g, 2.83 mmol). The solution was
kept at room temperature for 24 h. In order to complete the
precipitation of the salts as bromides, a saturated solution of
Et4NBr in acetonitrile was added to the reaction mixture until
no further precipitation was observed. The yellow precipitate
was filtered off, washed with acetonitrile, and subjected to
several column chromatographic runs (silica gel, CH3OH/
CH3NO2/2 N aqueous NH4Cl solution 7:2:1). The fractions
containing 7 were combined, and the solvent was removed in
vacuo. The residue was dissolved in water, and a saturated
1H NMR rates, 1 (0), 6.8 (0.047), 13.2 (0.085), 19.8 (0.142);
UV-vis rates, 1 (0), 5.1 (0.0274), 6.8 (0.0416), 8.34 (0.0596), 11.4
(0.0870), 17.8 (0.148).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR of com-
pounds 6, 7, and 5 (3 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O970702F
(11) Gender, W.; Hu¨nig, S.; Suchy, A. Tetrahedron 1986, 42, 1665.