Azolium-linked cyclophanes: Effects of structure, solvent, and counteranions on solution conformation behavior

Article abstract of DOI:10.1021/jo801860d

(Chemical Equation Presented) This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition of alkyl/alkoxy chain

Full text of DOI:10.1021/jo801860d

Azolium-Linked Cyclophanes: Effects of Structure, Solvent, and
Counteranions on Solution Conformation Behavior
Murray V. Baker,*,† David H. Brown,†,‡ Charles H. Heath,† Brian W. Skelton,†
Allan H. White,† and Charlotte C. Williams†
Chemistry M313, School of Biomedical, Biomolecular and Chemical Sciences, The UniVersity of Western
Australia, Crawley, WA 6009, Australia, and Nanochemistry Research Institute, Department of Applied
Chemistry, Curtin UniVersity of Technology, GPO Box U1987, Perth WA 6845, Australia
murray.baker@uwa.edu.au
ReceiVed August 21, 2008
This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-
linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition
of alkyl/alkoxy chains to the cyclophanes allows for studies in chlorinated solvents, whereas previous
solution studies of azolium cyclophanes have generally required highly polar solvents. The azolium
cyclophanes may exist in a syn/syn conformation (azolium rings mutually syn, arene rings mutually syn)
or a syn/anti conformation (azolium rings mutually syn, arene rings mutually anti). The preferred
conformation is significantly affected by (i) binding of bromide (ion pairing) to the protons on the
imidazolium or benzimidazolium rings, which occurs in solutions of bromide salts of the cyclophanes in
chlorinated solvents, and (ii) the addition of alkoxy groups to the benzimidazolium cyclophanes. These
structural modifications have also led to cyclophanes that adopt conformations not previously identified
for similar azolium cyclophane analogues. Detailed 1H NMR studies for one cyclophane identified binding
of bromide at two independent sites within the cyclophane.
Introduction
and 25 bind dihydrogenphosphate and fluoride preferentially,
respectively.
Over the past decade, azolium cyclophanes have been of
significant interest.1 Studies involving this class of cyclophanes
have focused on challenges associated with synthesis, their
intriguing conformational behavior, and, in particular, their
potential applications in anion recognition and, in the case of
imidazolium- and benzimidazolium-based cyclophanes, the use
of them as precursors to N-heterocyclic carbene metal complexes.
Anion binding involving imidazolium cyclophanes is prima-
rily based on hydrogen bonding of the anion with the acidic
H2 proton of the imidazolium cation.2-6 Design of specific
imidazolium cyclophane structures has led to cyclophanes that
display improved binding to specific anions; for example, 14
We have been interested in azolium cyclophanes containing
imidazolium or benzimidazolium moieties linked by xylyl
groups, for example, cyclophanes 3-5.7 These types of cyclo-
phanes can exhibit fluxional behavior in solution involving the
(3) (a) Yuan, Y.; Gao, G.; Jiang, Z.-L.; You, J.-S.; Zhou, Z.-Y.; Yuan, D.-
Q.; Xie, R.-G. Tetrahedron 2002, 58, 8993–8999. (b) Yoon, J.; Kim, S. K.;
Singh, N. J.; Kim, K. S. Chem. Soc. ReV. 2006, 35, 355–360. (c) Singh, N. J.;
Jun, E. J.; Chellappan, K.; Thangadurai, D.; Chandran, R. P.; Hwang, I.-C.; Yoon,
J.; Kim, K. S. Org. Lett. 2007, 9, 485–488. (d) Niu, H.-T.; Yin, Z.; Su, D.; Niu,
D.; Ao, Y.; He, J.; Cheng, J.-P. Tetrahedron 2008, 64, 6300–6306.
(4) Yoon, J.; Kim, S. K.; Singh, N. J.; Lee, J. W.; Yang, Y. J.; Chellappan,
K.; Kim, K. S. J. Org. Chem. 2004, 69, 581–583.
(5) Chellappan, K.; Singh, N. J.; Hwang, I.-C.; Lee, J. W.; Kim, K. S. Angew.
Chem., Int. Ed. 2005, 44, 2899–2903.
(6) Alcalde, E.; Mesquida, N.; Pe´rez-Garc´ıa, L. Eur. J. Org. Chem. 2006,
3988–3996.
† The University of Western Australia.
‡ Curtin University of Technology.
(1) For a review, see: Baker, M. V.; Brown, D. H. Mini-ReV. Org. Chem.
2006, 3, 333–354.
(2) Alcalde, E.; Alvarez-Ru´a, C.; Garc´ıa-Granda, S.; Garc´ıa-Rodriguez, E.;
Mesquida, N.; Pe´rez-Garc´ıa, L. Chem. Commun. 1999, 295–296.
(7) Baker, M. V.; Bosnich, M. J.; Brown, D. H.; Byrne, L. T.; Hesler, V. J.;
Skelton, B. W.; White, A. H.; Williams, C. C. J. Org. Chem. 2004, 69, 7640–
7652.
9340 J. Org. Chem. 2008, 73, 9340–9352
10.1021/jo801860d CCC: $40.75 2008 American Chemical Society
Published on Web 11/05/2008

Azolium-Linked Cyclophanes
solvents, paralleling the low solubility of the precursor azolium
cyclophane 3. We have attempted to improve the solubility of
the metal complexes in organic solvents by substitution of the
cyclophane skeleton with extended alkyl chains, and so have
explored the synthesis and properties of imidazolium cyclophane
salts such as 8-10.10,12,15 These cyclophanes (8-10) exhibit
remarkably different solubilities compared to the cyclophanes
3-5, readily dissolving in chlorinated solvents such as chlo-
roform and dichloromethane. The cyclophanes also exhibit
significantly different solution behavior in chlorinated solvents
1
compared to DMSO and methanol, as identified in H NMR
spectroscopy studies. This behavior appears to be a consequence
of halide interactions with the acidic imidazolium H2 protons
of the cyclophanes.
In this paper, we discuss the conformational behavior of
cyclophanes bearing extended alkyl chains. Our aim here is to
(i) understand the conformational behavior of the new alkyl-
substituted cyclophanes compared to the previously studied
systems; (ii) explore the effect of solvent on conformation; and
(iii) explore the effect of counteranions on the solution behavior
of the cyclophanes.
interconversion of different conformers.7,8 In some cases, during
low-temperature NMR studies, the fluxional behavior can be
“frozen-out” and the different conformers identified based on
their signals in the 1H NMR spectra. In general, azolium
cyclophanes such as 3-5 exhibit very low solubility in nonpolar
organic solvents, so the VT-NMR studies have been restricted
to solutions of the cyclophanes in highly polar solvents such as
DMSO and methanol.
Our interest in these salts is primarily based on their ability
to act as precursors to N-heterocyclic carbenes (NHCs) which
can form a range of metal complexes. For instance, we and
others have reported the synthesis and characterization of Pd(II)
(e.g., 6), Ni(II), Pt(II), Rh(I), Ir(I), Au(I) (e.g., 7), and Ag(I)
complexes with NHCs derived from azolium cyclophanes.9-16
The properties of these complexes are varied and include
catalytic behavior of Pd(II) complexes in Heck and Suzuki
reactions,10,11,15 Au(I) complexes that are luminescent and
exhibit potential antimitochondrial antitumor behavior,14,17 and
Ag(I) complexes that display antimicrobial activity.13,18 Com-
plexes such as 6 and 7 tend to exhibit low solubility in organic
(8) Bitter, I.; To¨ro¨k, Z.; Csokai, V.; Gru¨n, A.; Bala´zs, B.; To´th, G.; Keseru¨,
G. M.; Kova´ri, Z.; Czugler, M. Eur. J. Org. Chem. 2001, 2861–2868.
(9) (a) Shi, Z.; Thummel, R. P. Tetrahedron Lett. 1995, 36, 2741–2744. (b)
Garrison, J. C.; Simons, R. S.; Kofron, W. G.; Tessier, C. A.; Youngs, W. J.
Chem. Commun. 2001, 1780–1781. (c) Garrison, J. C.; Simons, R. S.; Talley,
J. M.; Wesdemiotis, C.; Tessier, C. A.; Youngs, W. J. Organometallics 2001,
20, 1276–1278. (d) Baker, M. V.; Skelton, B. W.; White, A. H.; Williams, C. C.
Organometallics 2002, 21, 2674–2678. (e) Garrison, J. C.; Simons, R. S.; Tessier,
C. A.; Youngs, W. J. J. Organomet. Chem. 2003, 673, 1–4. (f) Barnard, P. J.;
Baker, M. V.; Berners-Price, S. J.; Skelton, B. W.; White, A. H. Dalton Trans.
2004, 1038–1047. (g) Baker, M. V.; Brayshaw, S. K.; Skelton, B. W.; White,
A. H.; Williams, C. C. J. Organomet. Chem. 2005, 690, 2312–2322.
(10) Baker, M. V.; Skelton, B. W.; White, A. H.; Williams, C. C. J. Chem.
Soc., Dalton Trans. 2001, 111–120.
(11) Magill, A. M.; McGuinness, D. S.; Cavell, K. J.; Britovsek, G. J. P.;
Gibson, V. C.; White, A. J. P.; Williams, D. J.; White, A. H.; Skelton, B. W. J.
Organomet. Chem. 2001, 617-618, 546–560.
(12) Baker, M. V.; Brown, D. H.; Haque, R. A.; Skelton, B. W.; White,
A. H. Dalton Trans. 2004, 3756–3764.
(13) Melaiye, A.; Sun, Z.; Hindi, K.; Milsted, A.; Ely, D.; Renekerm, D. H.;
Tessier, C. A.; Youngs, W. J. J. Am. Chem. Soc. 2005, 127, 2285–2291.
(14) Barnard, P. J.; Wedlock, L. E.; Baker, M. V.; Berners-Price, S. J.; Joyce,
D. A.; Skelton, B. W.; Steer, J. H. Angew. Chem., Int. Ed. 2006, 5966–5970.
(15) Baker, M. V.; Brown, D. H.; Simpson, P. V.; Skelton, B. W.; White,
A. H.; Williams, C. C. J. Organomet. Chem. 2006, 691, 5845–5855.
(16) Baker, M. V.; Brown, D. H.; Hesler, V. J.; Skelton, B. W.; White, A. H.
Organometallics 2007, 26, 250–252.
The discussion in this paper is assisted by a brief summary
of the solution behavior of the previously studied cyclophane
salts 3·2Br-5·2Br.7,19 The variable-temperature 1H NMR
studies were performed using DMSO-d6 or CD3OD solutions.
The range of solvents was limited because of the low solubility
1
of these salts in organic solvents. The room-temperature H
NMR spectra of 3 · 2Br exhibited very broad signals for the
benzylic and imidazolium protons, the broad signals indicating
the probable occurrence of exchange processes. In DMSO-d6,
the H2 imidazolium proton is observed; however, in CD3OD,
the imidazolium H2 proton undergoes rapid H/D exchange and
is not observed.7 At low temperature, the exchange processes
were sufficiently slow that sharp 1H NMR signals were detected
for two different conformers, the structures of which were
1
determined from the chemical shifts of the signals in the H
NMR spectrum. In both conformers, the imidazolium rings were
mutually syn, but the benzene rings were anti in one conformer
and syn in the other (Scheme 1). Two different dynamic
processes were identified: rotation of the imidazolium rings
about their N-N axis, which interconverted the two different
(17) Barnard, P. J.; Baker, M. V.; Berners-Price, S. J.; Day, D. A. J. Inorg.
Biochem. 2004, 98, 1642–1647.
(18) Kascatan-Nebioglu, A.; Panzner, M. J.; Tessier, C. A.; Cannon, C. L.;
Youngs, W. J. Coord. Chem. ReV. 2007, 251, 884–895.
(19) Shi, Z.; Thummel, R. P. J. Org. Chem. 1995, 60, 5935–5945.
J. Org. Chem. Vol. 73, No. 23, 2008 9341

Baker et al.
SCHEME 1. Interconversion of the anti and syn Conformers of 3
TABLE 1. Rate Constant and Free Energy of Activation for the Exchange Processes of the Cyclophanes 3, 5, and 8
cyclophane
anion
solvent
anti:syna
k (antifantib)
∆Gq (antifanti)
k (antifsynb)
∆Gq (antifsyn)
3c
8
8
8
8
Br
Br
Br
PF6
PF6
CD3OD
CD3OD
CD2Cl2
CD3OD
CD2Cl2
0.78:0.22
0.74:0.26
1:0
0.81:0.19
0.85:0.15
740 s-1 @ -13 °C
775 s-1 @ -20 °C
104 s-1 @ 5 °C
49 kJ mol-1
48 kJ mol-1
57 kJ mol-1
47 kJ mol-1
53 kJ mol-1
120 s-1 @ 27 °C
160 s-1 @ 20 °C
d
61 kJ mol-1
59 kJ mol-1
d
677 s-1 @ -20 °C
82 s-1 @ -15 °C
107 s-1 @ 20 °C
84 s-1 @ 25 °C
60 kJ mol-1
61 kJ mol-1
5e
Br
DMSO-d6
61 kJ mol-1
a Population ratio at low exchange limit (low temp). b Processes: antifanti imidazolium ring rotation; antifsyn arene ring flip. c Ref 7. d Could not
be determined. Coalescence not reached. e Ref 19.
phenyl rings of the benzyl substituents are not positioned such
that their magnetic anisotropies should significantly influence
1
the imidazolium protons. The H NMR chemical shifts for
dibenzylimidazolium chloride, as reported in the literature, are
H2 δ 10.79 (CDCl3), 10.04 (DMSO-d6), 9.49 (D2O); H4/5 δ
7.34 (CDCl3), 7.97 (DMSO-d6), 7.70 (D2O).20,21 It should be
noted that in CDCl3 the signal for the imidazolium H2 proton
is considerably downfield (δ 10.79), presumably due to hydro-
gen bonding to the chloride counteranion. Crabtree and co-
FIGURE 1. The anti/syn conformation adopted by 4·2Br in solution
and in the solid state.
workers have reported that the chemical shift of the imidazolium
anti conformers, and flip of the benzene rings, which intercon-
verted the anti and syn conformers. The imidazolium ring
rotation process (antifanti exchange) was more facile than the
benzene ring flip process (antifsyn exchange), and rate
constants and activation energies for each process were esti-
mated from the variable-temperature NMR data (see the first
entry in Table 1).7 The benzimidazolium cyclophane 5·2Br
displayed behavior similar to that of 3·2Br, including broad
signals at room temperature, corresponding to the benzylic
protons, that coalesced at higher temperatures.7,19
The mesitylene-based cyclophane 4·2Br displayed very
different solution behavior. For solutions of 4·2Br in DMSO-
d6, sharp signals (including doublets for the benzylic protons)
in the 1H NMR spectra at all accessible temperatures indicated
the cyclophane to be rigid on the NMR timescale.7 The
cyclophane adopts an anti/syn conformation, with the imida-
zolium rings mutually syn and the arene rings mutually anti
(Figure 1). The anti/syn conformation was also identified in
X-ray crystallographic studies.
H2 proton in N,N′-dibutylimidazolium salts can be indicative
of ion pairing strengthsthe stronger the ability of the anion to
form hydrogen bonds, the further downfield the H2 signal [δ
10.45 (Br-), 9.85 (BF4-), 8.79 (PF6-), and 8.50 (SbF6-) in
CDCl3].22
Results and Discussion
Cyclophane Synthesis. The azolium-linked ortho and ortho/
meta imidazolium cyclophanes 8-10, as dibromide salts, were
prepared by standard procedures involving the reaction of a
bis(imidazolylmethyl)arene with a bis(bromomethyl)arene. The
preparations of these salts are reported elsewhere.7,10,12,15 The
butoxybenzimidazolium cyclophane salts 11·2Br and 12·2Br
were similarly prepared in excellent yield (79-84%) by the
reaction of the appropriate 1,2-bis(dibutoxybenzimidazolylm-
ethyl)benzene with 1,2-bis(bromomethyl)benzene. The precursor
dibutoxybenzimidazoles, 4,7-dibutoxybenzimidazole and 5,6-
dibutoxybenzimidazole, were synthesized in three-step se-
quences from 1,4-dibutoxybenzene and 1,2-dibutoxybenzene,
respectively (Scheme 2). Dinitration of 1,2-dibutoxybenzene
afforded 1,2-dibutoxy-4,5-dinitrobenzene,23,24 which was re-
duced with hydrazine hydrate and catalytic Pd/C,25 and the
The azolium cyclophane conformations can be determined
1
by analysis of their H NMR spectral data at slow-exchange
limits.1,7,8 The chemical shifts and multiplicities of the signals
attributed to the benzylic and imidazolium protons are particu-
larly useful. The magnetic anisotropy of aromatic rings can
significantly influence the chemical shifts of nearby protons.
For particular conformers, the aromatic groups of the cyclo-
phanes are positioned “above” (or “below”) the imidazolium
protons and can exert an electronic influence. The expected
chemical shift of the imidazolium protons, unaffected by the
magnetic anisotropy of nearby aromatic rings, can be based on
the chemical shifts of the dibenzylimidazolium cation since the
(20) Harlow, K. J.; Hill, A. F.; Welton, T. Synthesis 1996, 697–698.
(21) Claramunt, R. M.; Elguero, J.; Meco, T. J. Heterocycl. Chem. 1983,
20, 1245–1249.
(22) Kovacevic, A.; Gru¨ndemann, S.; Miecznikowski, J. R.; Clot, E.;
Eisenstein, O.; Crabtree, R. H. Chem. Commun. 2002, 2580–2581.
(23) Zhou, Z.-L.; Weber, E.; Keana, J. F. W. Tetrahedron Lett. 1995, 36,
7583–7586.
(24) Weinberger, L.; Day, A. R. J. Org. Chem. 1959, 24, 1451–1455.
(25) Rosa, D. T.; Reynolds, R. A., III.; Malinak, S. M.; Coucouvanis, D.
Inorg. Synth. 2002, 33, 112–119.
9342 J. Org. Chem. Vol. 73, No. 23, 2008

Azolium-Linked Cyclophanes
SCHEME 2. Synthesis of 5,6-Dibutoxybenzimidazole and 4,7-Dibutoxybenzimidazole
resulting diamine was treated with formic acid24 to afford 5,6-
dibutoxybenzimidazole. 4,7-Dibutoxybenzimidazole was pre-
pared similarly, but dinitration of 1,4-dibutoxybenzene afforded
a mixture of isomers, 1,4-dibutoxy-2,3-dinitrobenzene (major)
and 1,4-dibutoxy-2,5-dinitrobenzene (minor) in a ratio of ca.
4:1.26 The mixture was not separated at this step. Reduction of
the nitro groups was achieved using ammonium formate and
catalytic Pd/C in aqueous ethanol. Careful isolation and
purification at the end of the synthetic sequence afforded pure
4,7-dibutoxybenzimidazole.
8·2BPh4 and 8·2PF6, which contain counteranions that are
typically used to increase solubility of cations in organic media,
have solubility in organic solvents lower than that of 8·2Br.
For all the cyclophanes 8·2Br-12·2Br, there is evidence of
ion pairing between the (benz)imidazolium H2 protons and the
bromide ions in chlorinated solvents (see below). Such ion
pairing could make the cyclophanes more soluble in the less
polar organic solvents. In the case of the PF6- and BPh4- salts,
ion pairing would be limited, making the salts more ionic in
character.
Studies of Conformations in Solutions. Cyclophanes 8 ·
2Br, 8·2PF6, and 9 ·2Br. The room-temperature 1H NMR
spectra of solutions of 8·2Br and 9·2Br in DMSO-d6 or CD3OD
(e.g., Figures 2a and S1-S3 in the Supporting Information)
exhibit similar features to 1H NMR spectra for solutions of the
non-alkylated analogue 3·2Br, for example, broad signals
corresponding to the benzylic and imidazolium protons. Low-
temperature 1H NMR studies of 8·2Br (in CD3OD and
CH3OH27) indicated that, upon cooling, exchange processes
were slowed, and at -70 °C, two different conformers were
1
identifiable from the H NMR spectra (Figures 3a and S4-S6
in the Supporting Information), an anti conformer (arene rings
mutually anti), and a syn conformer (arene rings mutually syn),
analogous to the conformers exhibited by 3·2Br. At -70 °C,
both anti f syn and anti f anti exchange processes appeared
frozen-out. For 8·2Br in CD3OD, the ratio of anti to syn
conformers in solution at -70 °C was ca. 0.74:0.26, similar to
the ratio of ca. 0.78:0.22 seen for the non-alkylated analogue
In general, the “non-alkylated” cyclophanes 3·2Br-5·2Br
were very soluble in water, displayed low solubility in DMSO
and methanol, and were insoluble in organic solvents of medium
polarity such as acetone, chloroform, and dichloromethane. The
alkylated cyclophanes 8·2Br-12·2Br are much more hydro-
phobic and exhibit low solubility in water, good solubility in
acetone and THF, and excellent solubility in DMSO and
methanol. Remarkably, they also exhibit excellent solubility in
chloroform and dichloromethane, displaying higher solubility
in these solvents than in acetone and THF. In the cases of
8·2Br-10·2Br, the heptyl-substituted cyclophanes, the general
trend in solubility is 8·2Br > 9·2Br > 10·2Br. Interestingly,
FIGURE 2. 1H NMR spectra (500.1 MHz) of (a) 8·2Br in DMSO-d6,
(b) 8·2Br in CD2Cl2, and (c) 8·2PF6 in CD2Cl2, all recorded at 25 °C.
Key: x ) residual solvent signals, † ) H2O.
(26) Kawai, S.; Okawa, Y.; Yada, Y.; Hosoi, H.; Murakoshi, T.; Yajima, I.
Nippon Kagaku Zasshi 1959, 80, 551–555, CAN 55:17958.
J. Org. Chem. Vol. 73, No. 23, 2008 9343

Baker et al.
DMSO and methanol solutions. Detailed NMR studies indicate
that the appearance of NMR spectra for solutions containing
the cyclophane 8 can be interpreted in terms of the intercon-
version of the conformers and the ion pairing interactions
described in Figure 4. The experiments that lead to these
conclusions are summarized below.
Identification of the anti/anti Conformation of 8 in
CD2Cl2 Solutions of 8 ·2Br. Whereas solutions of 8·2Br and
9·2Br in DMSO-d6 display broad signals for the benzylic
protons and all the imidazolium protons, the room-temperature
1H NMR spectra of 8·2Br and 9·2Br in CD2Cl2 display very
broad signals attributable to the benzylic and imidazolium H4
and H5 protons, but a sharp, downfield signal for the imida-
zolium H2 protons (ca. δ 9.7) (e.g., Figures 2b, and S7 and S8
in the Supporting Information). This result suggests that, for
solutions of 8·2Br in CD2Cl2, the processes that interconvert
the predominant conformers in solution do not involve a change
to the environment of the imidazolium H2 protons.
Low-temperature 1H NMR spectra of 8·2Br in CD2Cl2
indicated the predominance of only one conformer at -40 °C
(Figures 3b and S9 in the Supporting Information). The signals
are sharp, indicating exchange processes to be very slow on
the NMR time scale. Two sets of AX patterns for the benzylic
protons (i.e., four doublets in total), one singlet for the
imidazolium H2 protons, two signals for the imidazolium H4
and H5 protons, and two singlets for the benzene protons
suggested one of only two possible conformations (Figure 5),
anti/anti (benzene groups mutually anti; imidazolium rings
mutually anti) or anti/syn (benzene groups mutually anti;
imidazolium rings mutually syn). Of particular note are the
chemical shifts of the imidazolium protons, δ 9.50 (H2) and δ
8.23 and 6.43 (H4 and H5). Compared with the chemical shift
of the H2 proton of dibenzylimidazolium chloride (H2 δ 10.79,
H4/5 δ 7.34 in CDCl320), the chemical shift of the imidazolium
H2 proton of 8·2Br (δ 9.50 in CD2Cl2) is significantly upfield.
This upfield shift is consistent with the protons being magneti-
cally shielded by an aromatic ring, a phenomenon that would
occur in both the anti/anti and anti/syn conformers. Likewise,
the chemical shifts of the signals for the imidazolium H4 and
H5 protons are significantly different, suggesting that only one
of those protons is magnetically shielded by an aromatic ring.
The symmetry in cyclophane 8 prevented definitive assignment
of which conformer was prevalent at low temperatures, but in
the similar cyclophane 9, the symmetry is reduced.
1
FIGURE 3. Downfield region of the H NMR spectra (500.1 MHz)
of 8·2Br (a) in CD3OD at -70 °C and (b) in CD2Cl2 at -40 °C. The
region shown in the dashed box is of a spectrum of 8·2Br in CH3OH
at -70 °C indicating signals for the H2 protons. Key: x ) residual
solvent signals.
3·2Br in CD3OD.7 On warming the solution of 8·2Br in
CD3OD, the 1H NMR spectra indicated the same behavior that
was identified in solutions of 3·2Br in CD3OD (see Figures S5
and S6 in the Supporting Information). Initially, a number of
the signals attributed to the anti conformers began to broaden
and eventually coalesced. On further heating, the signals due
to the syn conformer also broadened and coalesced with the
signals from the anti conformer. These results are consistent
with the operation of two distinct exchange processes, arene
ring flip and imidazolium ring rotation, analogous to those in
Scheme 1. Rate constants and activation energies for these
processes calculated from coalescence temperatures are sum-
marized in Table 1 (see Supporting Information for calculations).
The results are comparable to those obtained for the parent
cyclophane, 3·2Br (Table 1).7
A low-temperature 1H NMR study of 9·2Br in CD2Cl2
(Figure S10 in the Supporting Information) demonstrated that
at -40 °C two similar conformers were present in solution in
a ratio of ca. 2.8:1. The 1H NMR data (each conformer exhibited
one H2 signal near δ 9.5, four doublets for benzylic protons,
and one singlet and an AA′BB′ pattern for the two different
benzene rings) are consistent with both conformers being anti/
syn forms (benzene groups mutually anti; imidazolium rings
mutually syn, Figure 6). The identification of which of the two
different anti/syn conformers (A or B in Figure 6) was in highest
The above observations suggest that for solutions of 8·2Br
and 9·2Br in CD3OD or DMSO-d6 the alkylated cyclophanes
behave similarly to the non-alkylated analogue 3·2Br, displaying
the same exchange processes with similar populations of the
different conformers. This result is perhaps not unexpected,
given that the alkyl chains are located on the periphery of the
cyclophane structure and should not significantly influence the
different conformations.
The appearance of the room- and low-temperature 1H NMR
spectra for solutions of 8·2Br (and 9·2Br) in chloroform and
dichloromethane is in stark contrast to their appearance in
1
concentration at -40 °C could not be determined from the H
NMR spectra for 9·2Br in CD2Cl2.
The structural similarity between 8 and 9 and the similarities
in their NMR spectra (cf. Figures S9 and S10 in the Supporting
Information) suggest that, in CD2Cl2 solution, 8 also exists in
the anti/syn conformation.
(27) The (benz)imidazolium H2 protons undergo rapid H/D exchange with
CD3OD. Throughout our studies, we have also measured 1H NMR spectra of
solutions of the cyclophanes in CH3OH to determine the chemical shift of the
H2 protons. However, at room temperature, the H/H exchange of the H2 proton
with the hydroxyl proton of CH3OH is often so rapid that the signal attributed
to the H2 proton is too broad to be identified. At low temperatures, the process
is slower, and the signal attributed to the H2 protons can be identified.
Bromide Binding to the anti/anti Conformation of 8 in
CD2Cl2 Solutions of 8 ·2Br. The significance of ion-pairing
9344 J. Org. Chem. Vol. 73, No. 23, 2008

Azolium-Linked Cyclophanes
1
FIGURE 4. Main conformers of 8 and associated bromide binding inferred from H NMR spectral data: (a) conformations inferred from spectra
of solutions of 8·2PF6 in CD2Cl2 or 8·2Br in CD3OD (i.e., in the absence of ion pairing); (b) conformations inferred from spectra of 8·2PF6 in
CD2Cl2 with 1 equiv of Bu4NBr added; and (c) conformations inferred from spectra of CD2Cl2 solutions of either 8·2Br, or 8·2PF6 with 3 equiv
of Bu4NBr added. Chemical shifts indicated for imidazolium protons were obtained from spectra of (a) a solution of 8·2PF6 in CD2Cl2 at -70 °C,
Figure S14 in the Supporting Information; (b) a solution of 8·2PF6 in CD2Cl2 at -40 °C after the addition of 1 equiv of Bu4NBr, Figure S17 in
the Supporting Information; and (c) a solution of 8·2Br in CD2Cl2 at -40 °C, Figure S9 in the Supporting Information.
solutions of 8·2Br in methanol (anti-8 and syn-8 in Figure 4a).
The ratio of the two conformers was ca. 0.81:0.19 (anti:syn) in
methanol and ca. 0.85:0.15 (anti:syn) in CD2Cl2 (cf. 0.75:0.26
anti:syn for 8·2Br in methanol).
1
In the room-temperature H NMR spectrum of 8 · 2PF6 in
CD2Cl2 (Figure 2c), the H2 protons appeared as a very broad
signal near δ 7.9, but the corresponding signal for the imida-
zolium H2 protons for 8·2Br in CD2Cl2 as room temperature
was sharp and much further downfield (ca. δ 9.5, Figure 2b).
The large change in chemical shift for H2 (∆δ ) 1.6 ppm) can
FIGURE 5. Possible low-temperature conformers of 8·2Br in CD2Cl2,
1
be attributed to an interaction of a bromide counterion with the
imidazolium H2 proton in CD2Cl2 solution, which is absent in
the more strongly solvating DMSO-d6 and which has no
counterpart in CD2Cl2 solutions of 8·2PF6. A CD2Cl2 solution
containing 8·2PF6 and ca. 3 molar equiv of NBu4Br was
analyzed by 1H NMR spectroscopy over a range of temperatures
(Figure S15 in the Supporting Information), and the solution
behavior of the cyclophane 8 was identical to that of solutions
of 8·2Br in CD2Cl2 (Figure S16 in the Supporting Information).
The studies described above suggested that the presence of
ion paring between cyclophane 8 and bromide had a significant
influence on the solution behavior of 8. The stoichiometry of
binding between the cyclophane and the bromide anions was
investigated, initially by the method of continuous variations
(Job’s method; see Supporting Information).28 The change in
chemical shift for the H2 proton in a sample of 8·2PF6 in
CD2Cl2 in response to added bromide was used to generate a
Job plot (see Supporting Information). Analysis of this plot
suggested that a 1:1 (imidazolium cyclophane 8/bromide) ion
pair existed in solution.
based on available H NMR data. Comparison with data for 9·2Br
suggested that the predominant conformer for 8·2Br was the anti/syn
conformer.
To further explore this 1:1 ion pairing, a solution of 8·2PF6
with 1 equiv of NBu4Br in CD2Cl2 was examined by variable-
FIGURE 6. Possible low-temperature conformers of 9·2Br in CD2Cl2.
1H NMR data were consistent with the presence of only the anti/syn
conformers.
1
1
temperature H NMR spectroscopy. The H NMR spectrum
recorded at -40 °C (Figure S17a in the Supporting Information)
displayed signals consistent with two speciessone anti con-
former and one syn conformer (ca. 0.8:0.2 anti:syn)sthe
dynamic process that interconverts the species being frozen out
interactions on the solution behavior of 8 was revealed by a 1H
NMR investigation starting with the bromide-free salt 8·2PF6.
1
The H NMR spectra of 8·2PF6 in methanol and in CD2Cl2
were remarkably similar (Figures S11-S14 in the Supporting
Information). At low temperatures, both displayed signals
consistent with the presence of two different conformers in
solution: the anti and syn conformers identified previously in
(28) (a) Connors, K. A. Binding Constants. The Measurement of Molecular
Complex Stability; John Wiley & Sons: New York, 1987. (b) Schneider, H.-J.;
Yatsimirsky, A. Principles and Methods in Supramolecular Chemistry; John
Wiley & Sons: Chichester, UK, 2000.
J. Org. Chem. Vol. 73, No. 23, 2008 9345

Baker et al.
FIGURE 7. Predominant conformers in CD2Cl2 solution of 8·2Br and the imidazolium ring rotation process that converts the two conformers.
1
FIGURE 8. Selected H NMR chemical shift data for 10·2Br in (a) CDCl3 and (b) DMSO.
at this temperature. The NMR signals for both conformers were
consistent with only the H2 protons being involved in interac-
tions with bromide ions (e.g., anti-8· · ·Br and syn-8· · ·Br in
Figure 4b). The only significant differences between the
chemical shift data for anti-8 and anti-8· · ·Br, or syn-8 and syn-
8· · ·Br, is the downfield shift of the signal for the imidazolium
H2 protons (∆δ ) 1.7 ppm in each case, cf. Figure 4a,b).
However, despite the Job plot indicating a 1:1 binding stoichi-
ometry between 8 and bromide, the 1H NMR spectra of a
solution of 8·2PF6 with 1 equiv of NBu4Br in CD2Cl2, that is,
consisting of anti-8· · ·Br and syn-8· · ·Br, were not the same as
significantly influenced by bromide binding. Analysis of the
variable-temperature H NMR spectra for 8·2Br in CD2Cl2
1
(Figures S16 in the Supporting Information) permitted only
determination of the imidazolium ring rotation process (inter-
conversion of the two anti conformers, Figure 7). From
coalescence information, we estimate the rate constant for the
anti f anti exchange process to be 104 ( 4 s-1 at 5 °C and the
free energy of activation for this process to be 57 ( 1 kJ mol-1
(see Supporting Information for calculations). A comparison of
the kinetic data is presented in Table 1. When the cyclophane
8 is ion-paired with two bromide anions, as for anti-8· · ·2Br
(entry 3, Table 1), the rate constant for the imidazolium ring
rotation process is much lower and the free energy of
activation for this process is much highersby ca. 10 kJ
mol-1sthan in the absence of any cyclophane-bromide
pairing (entries 1, 2, and 4 in Table 1). It could be envisaged
that, with bromide binding to the imidazolium protons, the
bromide ions “hold” the imidazolium rings in the anti
conformation, a higher energy being required to break the
imidazolium · · · bromide interaction before imidazolium ring
rotation can occur (Figure 7). Similarly, bromide binding
slows the arene “ring flip” process that interconverts anti and
syn conformations of 8. Thus, whereas coalescence of benzylic
signals for 8 in the absence of bromide (Figures S19-S22 in
the Supporting Information) is indicative of interconversion of
anti and syn conformations, in the presence of bromide (Figure
S16 in the Supporting Information), while benzylic signals of
8 showed some broadening at high temperature, coalescence
did not occur at accessible temperatures. Alcalde et al. have
observed a similar “braking” effect for an imidazolium-linked
meta-xylyl cyclophane where the signals for the benzylic protons
of the cyclophane appeared as a singlet in the presence of
chloride or trifluoroacetate but appeared as two pairs of doublets
in the presence of hydroxide.6
1
the H NMR spectra of solutions of 8·2Br in CD2Cl2.
1
The only significant difference in H NMR chemical shifts
of anti-8· · ·Br in Figure 4b (from a solution of 8·2PF6 in CD2Cl2
after the addition of 1 equiv of NBu4Br) and anti-8 in Figure
4c (the only conformer detected in solutions of 8·2Br in CD2Cl2
at -40 °C) is the downfield shift of the signal for one of the
imidazolium H4/5 protons (δ ∼7.4 f δ 8.23; ∆δ ) 0.83 ppm).
This difference is consistent with the imidazolium H4/5 protons
interacting with an additional bromide ion when more than 1
equiv of bromide is present. In solutions of 8 in CD2Cl2 in the
presence of 2 or more equiv of bromide, the only cyclophane
species observed in solution is an anti conformer ion pairing
with two bromide ions, denoted as anti-8· · ·2Br (Figure 4c).
Presumably, unfavorable steric interactions that would ac-
company the binding of the second bromide ion to protons on
the “back” of the imidazolium ring prevents the observation of
a syn conformer (i.e., syn-8· · ·2Br).
In summary, there are two binding events for the cyclophane
8. In the first binding event, bromide binds to H2, while in the
second binding event, which only occurs after H2 is saturated,
bromide binds to H4/5. The analysis by Job’s method probes
the first binding event at room temperature. The second binding
event involves changes in signals that are too broad at room
temperature to be analyzed. As a result, the Job’s method
indicated a 1:1 binding stoichiometry (first binding event) while
the subsequent low-temperature investigation indicated an
overall 1:2 stoichiometry (first and second binding events).
It is interesting to consider the consequences of the ion
pairing. When ion pairing involves two bromide anions (as for
8 · 2Br in CD2Cl2), only one conformer of 8 is detectable in
solution, the interaction of the bromide anions favoring the anti
conformer anti-8· · ·2Br, whereas both anti and syn conforma-
tions are seen when ion pairing involves only one bromide. The
kinetics for the conformational exchange processes are also
Cyclophane 10 · 2Br. The solution behavior of 10 · 2Br in
DMSO-d6 at room temperature was similar to that of the non-
1
alkylated analogue 2·2Br. The H NMR spectra suggest that,
not unexpectedly, the only conformation seen for 10·2Br in
DMSO-d6 solution was the anti/syn arrangement (Figure 8). The
1H NMR spectra (Figure S23 in the Supporting Information)
displayed sharp signals, including four doublets for the benzylic
protons and a sharp singlet for the imidazolium H2 protons (at
δ 8.47), consistent with anti/syn conformer being rigid on the
NMR time scale. The upfield chemical shift of the imidazolium
H2 proton signal (δ 8.47, cf. δ 10.04 for dibenzylimidazolium
9346 J. Org. Chem. Vol. 73, No. 23, 2008

Azolium-Linked Cyclophanes
chloride in DMSO-d6) suggests that the imidazolium H2 protons
are affected by magnetic shielding from a nearby aromatic ring.
The spectra of 10·2Br in methanol exhibit some interesting
differences compared to the spectra of DMSO-d6 solutions. The
set of doublets corresponding to the benzylic protons of the ortho-
xylyl group is slightly broadened at room temperature (see
Figures S24 and S25 in the Supporting Information), while the
doublets for the benzylic protons on the mesitylene group are
sharp. The signal attributed to the imidazolium H2 proton (seen
in CH3OH solutions, but not seen in CD3OD solutions) is broad
at room temperature, but sharp at lower temperatures (Figures
S26 in the Supporting Information). A number of signals
broaden slightly as the temperature is lowered to 10 °C and
then sharpen as the temperature is lowered further, beyond -10
°C, but these effects are not accompanied by substantial changes
in chemical shifts or changes in the number of signals detected.
We do not know the cause of these subtle changes in the
variable-temperature NMR spectra of 10·2Br in methanol.
FIGURE 9. Two conformers of 11 and selected chemical shifts from
solutions of 11·2Br in methanol at -10 °C.
The spectra of 10·2Br in CDCl3 (see Figure S27 in the
Supporting Information) exhibit some differences compared to
the spectra of the DMSO-d6 or methanol solutions. The spectra
exhibit sharp signals independent of temperature, indicating a
structure that is rigid on the NMR time scale. Saturation transfer
1H NMR experiments on 10·2Br in CDCl3 at 40 °C showed no
evidence of slow exchange processes. The chemical shifts of
the signals for the imidazolium H4 and H5 protons are
significantly different in the two solvents (∆δ 1.71 ppm in
CDCl3, cf. ∆δ 0.2 ppm in DMSO-d6), and those of the
imidazolium H2 protons are significantly further downfield in
CDCl3 (δ 9.84, cf. δ 8.47 in DMSO-d6). These data are
consistent with an anti/syn conformation for 10 in both CDCl3
and DMSO-d6, but in CDCl3 with the presence of hydrogen
bonding between the imidazolium protons and bromide ions
(Figure 8), as was observed for 8.
Cyclophanes 11·2Br and 12 ·2Br. The butoxy-substituted
benzimidazolium cyclophanes 11 and 12 display significantly
different solution behavior compared to their imidazolium
analogues 8 and 9 discussed previously. In addition, the
structural variations between 11 and 12 result in these cations
exhibiting significantly different solution behaviors to each other
and, in the case of 12, induce a conformation not previously
identified for imidazolium/benzimidazolium cyclophanes linked
by ortho-xylyl groups.
1
FIGURE 10. Only conformation of 11 (with pertinent H chemical
shifts) detected in solutions of 11·2Br in CD2Cl2 at room temperature.
benzo ring of the benzimidazolium moiety (δ 7.25 for the syn
conformer and δ 6.13 and 7.32 for the anti).
The room-temperature 1H NMR spectra for solutions of
11·2Br in CD2Cl2 (Figure S31 in the Supporting Information)
exhibited sharp signals consistent with only one major conformer
in solution (the anti conformer in Figure 10). The downfield
chemical shift of the benzimidazolium H2 proton (δ 9.87, Figure
10) is consistent with the presence of hydrogen bonding between
the proton and a bromide anion. The signal is significantly
downfield (∆δ 1.3) by comparison with the chemical shift for
the equivalent proton of the anti conformer in methanolic
solutions (δ 8.61, Figure 9). It is interesting to note that in
methanol the predominant conformer is the syn conformer, yet
in the presence of bromide binding (in chlorinated solvents),
the anti conformer is predominant. It may be that the steric bulk
of the bromide ion destabilizes the syn conformation, where
binding of bromide to H2 would wedge the bromide ion between
two aromatic rings.
At room temperature, solutions of 11·2Br in DMSO-d6 and
methanol (Figures S28 and S29 in the Supporting Information)
exhibited numerous broad signals over the entire 1H NMR
spectrum. The signals were consistent with multiple conformers
undergoing exchange processes. Only in the case of the DMSO
solution could the temperature be raised sufficiently to achieve
coalescence of signals. The high freezing point of DMSO meant
that the slow exchange limit for spectra of 11 could not be
reached, so that the nature and relative populations of each of
Saturation-transfer 1H NMR experiments were conducted to
explore the possibility of slow-exchange processes involving
the anti conformer in solutions of 11·2Br in CD2Cl2 at 30 °C
(Figure S32 in the Supporting Information). Saturation of one
of the signals due to aromatic protons on the fused benzo ring
of the benzimidazolium moiety (e.g., δ 6.0, Figure 11) resulted
in a significant decrease in the intensity of the signal attributed
to the other proton on the benzo ring of the benzimidazolium
moiety (e.g., δ 8.0, Figures 11 and S32 in the Supporting
Information). Saturation of the signals corresponding to the exo
(or endo) benzylic protons did not change the intensity of the
signals for the corresponding endo (or exo) benzylic protons
by any appreciable amount. These results suggests that (i) the
benzimidazolium rings are undergoing partial rotation about their
N-N axes, interconverting two anti conformers in a process
that exchanges the environments of the two aromatic protons
1
the conformers could not be determined. H NMR spectra of
methanol solutions containing 11·2Br at -10 °C were sharp
(Figures S29 and S30 in the Supporting Information) and
consistent with the presence of two conformers in solutionsa
syn and an anti conformer (Figure 9) in the ratio of ca. 0.75:
0.25, respectively. The conformers were identified by the
1
numbers, patterns, and chemical shifts of the signals in the H
NMR spectra. Of particular note are the chemical shifts (Figure
9) of the benzimidazolium H2 protons (δ 7.41 for the syn
conformer and δ 8.61 for the anti) and the protons on the fused
J. Org. Chem. Vol. 73, No. 23, 2008 9347

Baker et al.
FIGURE 11. Benzimidazolium ring rotation (about the N-N axis) that
interconverts the two anti conformers of 11, as suggested by 1H NMR
saturation transfer studies of solutions of 11·2Br at room temperature.
FIGURE 13. The anti/anti conformer adopted in the solid state by
13.2
on the benzo-fused ring (Figure 11), but (ii) arene ring flip
processes that would exchange the environments of the benzylic
protons are not occurring at a measurable rate.
butyl chains also being interchanged, while the environments
of other protons are unaffected. This exchange presumably
occurs via a combination of both benzimidazolium ring rotation
and benzene ring flip processes, with other conformers as
(undetected) intermediates. The effective rate constant for the
interconversion of the two syn conformers is estimated at 719
The room-temperature 1H NMR spectra of solutions of
12·2Br in DMSO-d6 (Figure 12) exhibit sharp signals for the
phenyl protons (of the xylyl and benzimidazolium groups) and
the benzimidazolium H2 protons, but broadened doublets for
the benzylic protons, as well as broadened signals corresponding
to the methylene protons of the butyl chains. Of particular note
is the upfield chemical shift of the H2 proton (δ 7.11, Figure
12), which is consistent with magnetic shielding of this proton
by two aromatic rings. The spectra are consistent with 12
existing in a syn conformation. On heating the DMSO-d6
solutions, coalescence of the benzylic signals occurs (at ca. 70
°C), the signals for the methylene protons of the butyl chain
becomes sharp, and all other signals remain the same (Figure
12). These results are consistent with the existence of an
exchange process that interconverts two equivalent syn confor-
mations of 12 (Figure 12). This exchange process results in the
environments of the benzylic protons to be interchanged and
the environments of the diastereotopic methylene protons of the
( 9 s-1 at 70 °C with an activation energy of 66 ( 2 kJ mol-1
.
1
Interestingly, the H NMR spectra of 12·2Br in methanol
display sharp signals over a broad temperature range consistent
with a single frozen-out conformation (syn). (The spectrum
shown in Figure S34 in the Supporting Information is repre-
sentative of the spectra over the broad temperature range.) At
50 °C, the benzylic doublets start to broaden, suggesting the
occurrence of very slow exchange processes. The signal for the
benzimidazolium H2 proton (δ 7.2), observable in CH3OH
solutions, is sharp only at low temperature being broadened at
high temperatures, presumably due to rapid H-H exchange with
the methanol hydroxyl proton. The spectral features are sug-
gestive again of only a single syn conformer in solution. The
1H NMR spectra of 12·2Br in CDCl3 (Figure S35 in the
1
FIGURE 12. Variable-temperature H NMR spectra (500.1 MHz, DMSO-d6) of 12·2Br. Key: x ) residual solvent signal, † ) H2O. See Figure
S33 in the Supporting Information for additional spectra.
9348 J. Org. Chem. Vol. 73, No. 23, 2008

Azolium-Linked Cyclophanes
FIGURE 14. Unit cell contents of 11·2Br·5H2O, projected down b, showing hydrogen bonding.
j
Supporting Information) are almost identical to those in
methanol. The signal for the benzimidazolium H2 proton of 12
is still relatively upfield (δ 7.2), consistent with the H2 protons
being magnetically shielded by two benzene rings (i.e., a syn
conformation for 12) and not being involved in ion pairing
interactions with bromide counterions. Presumably, the butyl
substituents in 12 favor the syn conformation of the cyclophane
by sterically hindering the approach of the benzene groups to
the benzimidazolium groups. In the syn conformation, the
benzene groups prevent approach of bromide ions to the H2
protons, thereby eliminating ion-pairing effects at the H2 site.
Saturation transfer experiments conducted for a solution of
12·2Br in CDCl3 suggest the existence of an exchange process
that interconverts two equivalent syn conformations (Figure 12),
but which was only detectable at temperatures above room
temperature.
The benzimidazolium cyclophanes 11 and 12 are the only
ortho-xylyl-linked imidazolium/benzimidazolium cyclophanes
that have exhibited syn conformers where the azolium C2-H2
bond points into the cavity between aromatic rings. These two
cyclophanes also adopt the syn conformation in preference to
an anti conformation, whereas for other ortho-xylyl-linked
imidazolium cyclophanes, the anti conformation is dominant.
The benzimidazolium cyclophanes 11 and 12 also display some
of the slowest dynamic behavior identified for ortho-xylyl-linked
imidazolium/benzimidazolium cyclophanes.
Solid-State Structural Studies. Attempts to grow crystals
of 8·2Br or 8·2PF6 suitable for crystallographic studies proved
unsuccessful. It was, however, possible to grow crystals of the
tetraphenylborate salt 8·2BPh4, although the limited solubility
of the salt prevented low-temperature 1H NMR studies of
solutions of the salt. It is interesting to note that, despite the
dominant solution conformer of 8 (regardless of counteranion
or solvent) being anti/syn (arenes mutually anti and imidazolium
rings mutually syn), in the solid-state crystallographic study of
8·2BPh4, the cyclophane adopts an anti/anti conformation
(Figure S51 in the Supporting Information). One half of the
formula unit comprises the asymmetric unit in a triclinic P1
unit cell, and an inversion center lies between the pair of
imidazolium rings. Alcalde et al. have reported the solid-state
structure of an imidazolium-linked meta-xylyl cyclophane (13),
which, when crystallized as the chloride salt, adopted a anti/
anti conformation with one imidazolium H2 · · ·chloride hydro-
gen bond (as displayed in Figure 13).2
The present studies of the bromide salts of 11 and 12 are
modeled in terms of adducts which are quite heavily hydrated,
11·2Br·5H2O and 12·2Br·4H2O, all hydroxylic hydrogen
atoms being located in difference maps (11·2Br·5H2O) or
refinable in (x,y,z,Uiso)H (12·2Br·4H2O). In 11·2Br·5H2O
(where one formula unit, devoid of crystallographic symmetric,
comprises the asymmetric unit of the structure), the two
imidazole hydrogen atoms contact a bromide ion (H · · ·Br 2.92
Å (est.)) and a water molecule oxygen atom (H · · ·O 2.32 Å
(est.)), a hydrogen-bonded column being formed parallel to b
(Figure 14). Interestingly, water molecule 2 is “sandwiched”
between the phenyl rings (H· · ·centroid distances 2.43, 2.68 Å
(est.)) with the centroid-centroid distance being 6.05 Å (est.)
(Figure 15). In 12·2Br·4H2O, where only one imidazole
hydrogen atom is crystallographically independent (the cation
being disposed about a crystallographic 2-axis in monoclinic
space group C2/c), the contact is to a bromide ion (H · · · Br
3.08(3) Å). Here, no entity is sandwiched, the intercentroid
distance being 4.94 Å and the phenyl rings obligate parallel
(Figure S53 in the Supporting Information). The cations pack
in columns parallel to c, with a pronounced layering normal to
that axis, consisting of alternate sheets of cations interspaced
by anions and solvent molecules, hydrogen-bonded (Figure S49
and S50 in the Supporting Information). Full details of hydrogen
bonding schemes for 11·2Br·5H2O and 12·2Br·4H2O are given
in the Supporting Information. The crystal packing in 8·2BPh4
is also of interest in that the heptyl substituents are disposed
parallel to and either side of the ab plane, the latter layering
the structure (Figure S54 in the Supporting Information). The
anions embrace pairwise about inversion centers (1/2, 0, 1/2).
J. Org. Chem. Vol. 73, No. 23, 2008 9349

Baker et al.
here.7,10,12,15 1,2-Bis(bromomethyl)-1,2-diheptylbenzene and 1,2-
bis(imidazol-1-ylmethyl)-4,5-diheptylbenzene were prepared by the
method of Baker et al.12 1,2-Dibutoxy-4,5-dinitrobenzene23,24 and
crude 1,4-dibutoxy-2,3-dinitrobenzene26 (as a mixture containing
ca. 20 mol % of 1,4-dibutoxy-2,5-dinitrobenzene) were prepared
by literature procedures. Where detailed assignment of 13C NMR
spectra is provided below, these assignments have been made with
1
the aid of HSQC (1-bond H-13C correlation) and HMBC (2/3-
1
bond H-13C correlation) 2D NMR experiments.
Full 1H NMR details for the imidazolium and benzimidazolium
cyclophanes are provided in Supporting Information.
1,1′,3,3′-Bis(4,5-diheptyl-o-xylyl)diimidazolium dibromide 8 ·2Br.
Solutions of 1,2-bis(imidazol-1-ylmethyl)-4,5-diheptylbenzene (1.0
g, 2.3 mmol) in acetone (50 mL) and crude 1,2-bis(bromomethyl)-
1,2-diheptylbenzene (1.06 g) in acetone (50 mL) were added
portionwise, simultaneously, to acetone (180 mL) heated at reflux
over the course of 5 h. The mixture was then heated at reflux for
4 days. The volume of solvent was concentrated by ca. 120 mL
and then cooled to rt. The resulting precipitate was collected, washed
with acetone, and dried to afford a white powder (1.09 g, 53%):
C50H78N4Br2 ·2H2O requires C, 64.50; H, 8.88; N, 6.02%. Found:
C, 64.71; H, 9.04; N, 5.95; δC (CDCl3, 125.8 MHz, 298 K) 14.0
(CH3), 22.6, 29.0, 29.7, 30.8, 31.7, 32.3 (6 × CH2), 51.7 (br,
benzylic CH2), 119.9 (v br), 124.3 (v br), 128.6 (v br), 134.6 (CH),
135.6 (CH), 145.0 (v br); m/z (ES CH2Cl2) 813.5225 (M - Br)
(C50H78N481Br requires 813.5233).
1,1′,3,3′-Bis(4,5-diheptyl-o-xylyl)diimidazolium bis(hexafluoro-
phosphate) 8 ·2PF6. A solution of 8·2Br (257 mg, 0.29 mmol) in
methanol (25 mL) and water (10 mL) was added to a solution of
potassium hexafluorophosphate (0.7 g, 3.8 mmol) in methanol (25
mL) and water (10 mL). The mixture was stirred for 1 h and was
then diluted with water (40 mL). The resulting precipitate was
collected, washed with water (20 mL), and dried to afford a white
powder (255 mg, 86%). C50H78N4P2F12 ·0.1H2O requires C, 58.48;
H, 7.68; N, 5.46%. Found: C, 58.09; H, 7.95; N, 5.14.
FIGURE 15. Projection of the cation 11, with associated anion and
water molecules (see also Figure S52 in the Supporting Information).
The phenyl rings of the cation are surrounded by those of the
anion in edge-to-face contact.
Conclusions
The structure of azolium-linked cyclophanes, the types of
counteranions, and the particular solvents in which the cyclo-
phanes are studied can have a significant influence on the
conformers observed and the rates of the processes that may
interconvert them. The incorporation of alkyl chains onto the
periphery of the imidazolium cyclophanes has extended the
solubility of the cyclophanes to allow studies in chlorinated
solvents. With noncoordinating counteranions, the solution
behaviors of the alkylated cyclophanes in chlorinated solvents
were found to be similar to that of the cyclophanes with bromide
counteranions in polar solvents such as methanol and DMSO.
In chlorinated solvents, however, the presence of bromide
counteranions impacts on the behavior of the cyclophanes. Thus,
in the case of the ortho-linked imidazolium cyclophane 8, only
a single anti conformer was detected in solution, with the
cyclophane forming ion pairs with two bromide anions. Not
only did the bromide ions influence the solution conformation
but the cyclophane · · ·bromide interactions significantly impacted
the activation barrier for the processes that interconvert the
solution conformers, by making rotation of the imidazolium
rings about their N-N axes more difficult.
In the case of the butoxy-benzimidazolium systems, the
position of the butoxy fictionalization has a significant influence
on the conformations adopted by the cyclophanes. Particularly
in the case of 12, the preferred conformer is a syn conformer
where the benzimidazolium H2 protons are directed into the
cavity formed by the two ortho-xylyl groups. This is the first
time such a conformation has been identified for azolium-linked
ortho-cyclophanes and suggests interesting possibilities with
respect to the formation of N-heterocyclic carbene metal
complexes derived from such carbene precursors. We are
currently exploring the metal complexation of N-heterocyclic
carbenes derived from these benzimidazolium cyclophanes and
related species.
We have previously reported the synthesis of 8·2Br and 8·2BPh4
and the mass and NMR [in (CD3)2SO solutions] spectral data of
8·2Br.10 Single crystals of 8·2BPh4 suitable for X-ray diffraction
studies were grown by slow evaporation of an acetone solution of
the cyclophane.
5,6-Dibutoxybenzimidazole (14). Hydrazine hydrate (41 mL, 0.84
mol) was added slowly to a stirred mixture of 1,2-dibutoxy-4,5-
dinitrobenzene (26.5 g, 85 mmol) and palladium on carbon (0.59
g, 10% Pd/C) in ethanol (250 mL). After the addition was complete,
the mixture was heated at reflux for 14 h. The mixture was cooled
and filtered through Celite under a nitrogen atmosphere. The filtrate
was concentrated in vacuo to afford a yellow solid (ca. 21 g of
crude 1,2-dibutoxy-4,5-diaminobenzene). The solid was dissolved
in formic acid (100 mL, 90%), and the resulting solution was heated
at reflux for 3 h. The mixture was diluted with aqueous ammonia
solution (50 mL, 28%) and then aqueous sodium carbonate solution
(140 g in 1000 mL). The resulting precipitate was collected, washed
with water (2 × 100 mL), and air-dried to afford a pale brown
solid. The solid was dissolved in toluene (250 mL), and the mixture
was dried by azeotropic distillation of water. The resulting toluene
solution was concentrated to ca. 150 mL and diluted with hexanes
(50 mL). The resulting precipitate was collected, washed with
hexanes (100 mL), and dried to afford a pale brown powder (18 g,
80%). C15H22N2O2 requires C, 68.67; H, 8.45; N, 10.68%. Found:
C, 68.73; H, 8.50; N, 10.49; δH [(CD3)2SO, 300.1 MHz] 0.94 (6H,
3
t, JH,H 7.4 Hz, 2 × CH3), 1.47 (4H, m, 2 × CH2CH3), 1.71 (4H,
3
m, 2 × OCH2CH2), 3.95 (4H, t, JH,H 6.4 Hz, 2 × OCH2), 7.03
and 7.16 (2H, 2 × br s, 2 × Ar H), 7.98 (1H, s, NCHN), and 12.1
(1H, s, NH); δC [(CD3)2SO, 75.5 MHz] 13.8 (CH3), 18.8 (CH2),
31.0 (CH2), 68.7 (OCH2), 96.6 (br, Ar C), 104.1 (br, Ar C), 127.1
(br, Ar C), 136.7 (br, Ar C), 140.3 (NCHN), 145.6 (br, Ar C), and
146.5 (br, Ar C).
Experimental Section
General Procedures and Materials. General experimental pro-
cedures have been described previously.12,16 The synthesis of the
cyclophane salts 8·2Br, 9·2Br, and 10·2Br has been reported
previously, though an improved synthesis of 8·2Br is reported
1,2-Bis(5′,6′-dibutoxybenzimidazolyl-1′-methyl)benzene (15).
Sodium hydride (0.6 g, 15 mmol; 60% dispersion in oil) was added
9350 J. Org. Chem. Vol. 73, No. 23, 2008

Azolium-Linked Cyclophanes
to a solution of 5,6-dibutoxybenzimidazole (14) (3.36 g, 12.8 mmol)
in dry THF (150 mL). The mixture was stirred for 30 min. To the
resulting solution was added a solution of 1,2-bis(bromomethyl)-
benzene (1.69 g, 6.4 mmol) in dry THF (30 mL). The mixture was
then heated at reflux for 18 h. The mixture was cooled and then
filtered through a plug of Celite and basic alumina. The filtrate
was concentrated in vacuo, and the residue was triturated with hot
hexanes (150 mL) to afford a white solid (3.65 g, 91%). C38H50N4O4
requires C, 72.81; H, 8.04; N, 8.94%. Found: C, 72.72; H, 8.12;
1,2-Bis(4′,7′-dibutoxybenzimidazolyl-1′-methyl)benzene (17).
Sodium hydride (0.52 g, 13 mmol; 60% dispersion in oil) was added
to a mixture of 4,7-dibutoxybenzimidazole (16) (2.49 g, 9.5 mmol)
in dry THF (120 mL). The mixture was stirred for 40 min. To the
resulting solution was added a solution of 1,2-bis(bromomethyl)-
benzene (1.39 g, 5.25 mmol) in dry THF (45 mL). The mixture
was then heated at reflux overnight. The mixture was cooled and
then filtered through a plug of Celite. The filtrate was concentrated
in vacuo; the residue was dissolved in ethyl acetate (150 mL), and
the solution was filtered through a plug of silica. The filtrate was
concentrated in vacuo, and the residue was triturated with hot
hexanes (175 mL). The mixture was cooled; the solution was
decanted, and the solid was triturated again with hot fresh hexanes
(50 mL). After cooling, the solid was collected and recrystallized
by dissolving the solid in dichloromethane (5 mL) and layering
the solution with hexanes (100 mL), which afforded off-white
crystals (2.12 g, 71%). C38H50N4O4 requires C, 72.81; H, 8.04; N,
8.94%. Found: C, 72.65; H, 7.90; N, 8.74; δH [(CD3)2SO, 500.1
3
N, 8.70; δH (CDCl3, 300.1 MHz) 0.94 (6H, t, JH,H 7.4 Hz, 2 ×
3
CH3), 0.97 (6H, t, JH,H 7.4 Hz, 2 × CH3), 1.49 (8H, m, 4 ×
CH2CH3), 1.74 (4H, m, 2 × OCH2CH2), 1.81 (4H, m, 2 ×
3
OCH2CH2), 3.80 (4H, t, JH,H 6.5 Hz, 2 × OCH2), 4.01 (4H, t,
3JH,H 6.5 Hz, 2 × OCH2), 5.17 (4H, s, 2 × benzylic CH2), 6.48
(2H, s, 2 × benzimidazole Ar CH), 7.03-7.10 (2H, AA′ part of
AA′XX′ pattern, xylyl Ar 3-CH and 6-CH), 7.27 (2H, s, 2 ×
benzimidazole Ar CH), 7.30-7.37 (2H, XX′ part of AA′XX′
pattern, xylyl Ar 4-CH and 5-CH), and 7.64 (2H, s, 2 × NCHN);
δC (CDCl3, 75.5 MHz) 13.8 (CH3), 19.18 (CH2CH3), 19.23
(CH2CH3), 31.22 (CH2), 31.24 (CH2), 46.4 (benzylic CH2), 69.3
(OCH2), 69.5 (OCH2), 94.7 (benzimidazole CH), 104.3 (benzimi-
dazole CH), 127.6 (benzimidazole C), 129.16 (xylyl Ar CH C3/6),
129.22 (xylyl Ar CH C4/5), 133.1 (xylyl Ar C C1/2), 137.1
(benzimidazole C), 141.0 (NCHN), 147.1 (benzimidazole C-O),
and 147.8 (benzimidazole C-O).
3
3
MHz] 0.74 (6H, t, JH,H 7.4 Hz, 2 × CH3), 0.95 (6H, t, JH,H 7.4
Hz, 2 × CH3), 1.08-1.16 (4H, m, 2 × CH2CH3), 1.41-1.52 (8H,
2 × m, 2 × OCH2CH2 and 2 × CH2CH3), 1.71-1.76 (4H, m, 2 ×
3
OCH2CH2), 3.88 (4H, t, JH,H 6.5 Hz, 2 × OCH2), 4.12 (4H, t,
3JH,H 6.5 Hz, 2 × OCH2), 5.75 (4H, s, 2 × benzylic CH2), 6.58
3
(2H, d, JH,H 8.6 Hz, 2 × benzimidazole Ar 7′-CH), 6.63 (2H, d,
3JH,H 8.6 Hz, 2 × benzimidazole Ar 6′-CH), 6.67-6.71 (2H, AA′
part of AA′XX′ pattern, xylyl Ar 3-CH and 6-CH), 7.16-7.20 (2H,
XX′ part of AA′XX′ pattern, xylyl Ar 4-CH and 5-CH), and 7.95
(2H, s, 2 × NCHN); δC [(CD3)2SO, 125.8 MHz] 13.6 (CH3), 13.8
(CH3), 18.5 (CH2CH3), 18.8 (CH2CH3), 30.5 (OCH2CH2), 31.1
(OCH2CH2), 46.5 (benzylic CH2), 67.9 (OCH2), 68.2 (OCH2), 104.3
(benzimidazole 5′-CH), 104.4 (benzimidazole 6′-CH), 124.9 (ben-
zimidazole 8′-C), 126.4 (xylyl Ar 3-CH and 6-CH), 127.7 (xylyl
Ar 4-CH and 5-CH), 135.1 (xylyl Ar 1-C and 2-C), 135.7
(benzimidazole 9′-C), 140.6 (benzimidazole B-CO), 143.0 (NCHN),
and 144.8 (benzimidazole A-CO).
1,1′,3,3′-Bis(o-xylyl)bis(5′,6′-dibutoxybenzimidazolium) dibro-
mide 11 ·2Br. Solutions of 1,2-bis(5′,6′-dibutoxybenzimidazolyl-
methyl)benzene (15) (1.67 g, 2.7 mmol) in acetone (50 mL) and
1,2-bis(bromomethyl)benzene (0.716 g, 2.7 mmol) in acetone (50
mL) were added portionwise, simultaneously, to acetone (200 mL)
heated at reflux over the course of 7 h. The mixture was then heated
at reflux overnight. The volume of solvent was concentrated by
ca. 100 mL and then cooled to rt. The resulting precipitate was
collected, washed with acetone, and dried to afford a white powder
(1.9 g, 79%), which can be recrystallized from methanol/water
solutions. C46H58N4O4Br2 ·2H2O requires C, 59.61; H, 6.74; N,
6.05% Found: C, 59.43; H, 6.51; N, 5.77; δC (CDCl3, 75.5 MHz)
13.8 and 14.0 (CH3), 19.1 and 19.3 (CH2CH3), 30.8 and 31.0 (CH2),
50.7 and 52.0 (benzylic CH2), 69.6 and 70.4 (OCH2), 96.3 and 97.4
(benzimidazolium CH), 123.8 and 125.9 (benzimidazolium C),
132.3 and 134.8 (xylyl Ar CH C3/6), 130.7 and 134.3 (xylyl Ar
CH C4/5), 131.3 and 133.7 (xylyl Ar C C1/2), 137.6 (NCHN), 149.2
(benzimidazolium C-O), and 150.5 (benzimidazolium C-O).
4,7-Dibutoxybenzimidazole (16). Palladium on carbon (10%,
0.4 g) was added to a mixture of crude 1,4-dibutoxy-2,3-dinitroben-
zene (6.6 g of mixture, ca. 17 mmol of 1,4-dibutoxy-2,3-dinitroben-
zene) and ammonium formate (24 g, 0.38 mol) in water (40 mL)
and ethanol (180 mL). The mixture was heated at ca. 60 °C for
1.25 h with stirring under a nitrogen atmosphere. The mixture was
allowed to cool and was then filtered through Celite under nitrogen.
The filtrate was concentrated in vacuo. The residue was treated
with formic acid (90%, 66 mL), and the resulting mixture was
heated at reflux for 2 h. The mixture was then allowed to cool
overnight and was then filtered (byproduct crystallize/precipitate
with slow cooling). The filter cake was washed with formic acid
(90%, 20 mL). The formic acid solutions were combined and then
treated with aqueous ammonia (28%, 200 mL). The resulting solid
was collected and recrystallized from ethyl acetate (including
treatment with activated carbon) to afford off-white crystals (2.5
g, 56%). C15H22N2O2 requires C, 68.67; H, 8.45; N, 10.68%. Found:
C, 68.43; H, 8.17; N, 10.56; δH [(CD3)2SO, 300.1 MHz] 0.94 (6H,
1,1′,3,3′-Bis(o-xylyl)bis(4′,7′-dibutoxybenzimidazolium)dibro-
mide 12 ·2Br. Solutions of 1,2-bis(4′,7′-dibutoxybenzimidazolyl-
methyl)benzene (17) (1.44 g, 2.3 mmol) in acetone (60 mL) and
1,2-bis(bromomethyl)benzene (0.67 g, 2.5 mmol) in acetonitrile (60
mL) were added portionwise, simultaneously, to acetonitrile (500
mL) heated at reflux over the course of 6.5 h. The mixture was
then heated at reflux overnight. The mixture was concentrated in
vacuo. The residue was recrystallized by dissolving the solid in
chloroform (8 mL) and layering the solution with ethyl acetate (110
mL), which afforded colorless crystals (1.72 g, 84%).
C46H58N4O4Br2 ·3H2O requires C, 58.48; H, 6.83; N, 5.93%. Found:
C, 58.65; H, 6.63; N, 5.66; δC (CDCl3, 125.8 MHz) 13.9 (CH3),
19.3 (CH2CH3), 31.3 (OCH2CH2), 51.2 (benzylic CH2), 70.1
(OCH2), 109.0 (benzimidazolium 5′-CH and 6′-CH), 121.8 (ben-
zimidazolium C), 131.4 (xylyl 1-C and 2-C), 131.9 (xylyl 4-C and
5-C), 134.8 (xylyl 3-C and 5-C), 140.3 (NCHN), and 141.3
(benzimidazolium C-O).
Structure Determinations. Full spheres of “low”-temperature
CCD area detector diffractometer data were measured (Bruker AXS
instrument, ω-scans; monochromatic Mo KR radiation; λ ) 0.71073
Å), yielding Nt(otal) reflections, these merging to N unique (Rint cited)
after “empirical”/multiscan absorption correction (proprietary soft-
ware), No with F > 4σ(F) being considered “observed” and used
in the full matrix least-squares refinements on F2; anisotropic
displacement parameter forms were refined for the non-hydrogen
atoms, hydrogen atom treatment following a “riding” model. Neutral
atom complex scattering factors were employed within the Xtal
3.7 and SHELXL97 programs;29 individual variations in procedure
are noted as “variata”. Pertinent results are given below and in the
text and figures and the Supporting Information; full.cif depositions
(excluding structure factor amplitudes) are deposited with the
Cambridge Crystallographic Data Centre, CCDC 653544-653546.
3
t, JH,H 7.4 Hz, 2 × CH3), 1.48 (4H, m, 2 × CH2CH3), 1.73 (4H,
3
m, 2 × OCH2CH2), 4.05 (2H, t, JH,H 6 Hz, OCH2), 4.12 (2H, t,
3JH,H 6 Hz, OCH2), 6.51 (1H, d,3JH,H 8 Hz, Ar H), 6.59 (1H, d,3JH,H
8 Hz, Ar H), 8.00 (1H, s, NCHN), and 12.62 (1H, s, NH); δC
[(CD3)2SO, 75.5 MHz] 13.8 (CH3), 18.76, 18.81 (2 × CH2), 31.0,
31.1 (2 × CH2), 67.8, 68.2 (2 × OCH2), 103.9 (2 × Ar CH), 125.1
(Ar C), 135.0 (Ar C), 139.98 (Ar C), 140.01 (NCHN), and 144.7
(Ar C).
j
8·2BPh4: C98H118B2N4, Mr ) 1373.7; triclinic, space group P1,
a ) 10.212(2), b ) 10.986(2), c ) 19.149(3) Å, R ) 73.713(2), ꢀ
J. Org. Chem. Vol. 73, No. 23, 2008 9351

Baker et al.
) 80.078(3), γ ) 78.970(3)°, V ) 2008 Å3; Dc (Z ) 1) ) 1.136 g
cm-3; µMo ) 0.06 mm-1; specimen: 0.65 × 0.08 × 0.02 mm; Tmin/
max ) 0.84; 2θmax ) 58°; Nt ) 20164, N ) 9877 (Rint ) 0.039), No
) 5532; R ) 0.049, Rw ) 0.040; T ca. 153 K.
Variata. All hydrogen atoms were refined in (x,y,z,Uiso)H (refine-
ment on |F|).
vacation scholarship (to C.H.H.), and Curtin University of
Technology for a Research and Teaching Fellowship (to
D.H.B.).
Supporting Information Available: Tables of 1H NMR data
1
and H NMR spectra for the cyclophane salts 8·2Br, 8·2PF6,
11·2Br·5H2O: C46H68Br2N4O7, Mr ) 980.9; triclinic, space group
9·2Br, 10·2Br, 11·2Br, and 12·2Br in various solvents
including DMSO-d6, CD3OD, CH3OH, CD2Cl2, and CDCl3; Job
plot information for 8; details about the estimation of rate
constants and activation energies for dynamic NMR experi-
j
P1, a ) 9.051(2), b ) 10.069(2), c ) 27.751(5) Å, R ) 80.531(3),
ꢀ ) 80.729(3), γ ) 80.473(3)°, V ) 2437 Å3; Dc (Z ) 2) ) 1.337
g cm-3; µMo ) 1.7 mm-1; specimen: 0.68 × 0.08 × 0.06 mm;
Tmin/max ) 0.88; 2θmax ) 50°; Nt ) 23127, N ) 8540 (Rint ) 0.087),
No ) 6244; R ) 0.056, Rw ) 0.12; T ca. 153 K.
1
ments; 13C NMR spectra for 8·2Br, 11·2Br, and 12·2Br; H
and 13C NMR spectra for 14, 15, 16, and 17; tables detailing
the hydrogen bonding in the solid-state structures of 11·2Br
and 12·2Br; figures of the unit cells and hydrogen bonding for
11·2Br·5H2O and 12·2Br·4H2O; and figures containing atom
labels for the solid-state structures of cations 8, 11, and 12. This
material is available free of charge via the Internet at
http://pubs.acs.org.
12·2Br·4H2O: C46H66Br2N4O8, Mr ) 962.9; monoclinic, space
group C2/c, a ) 20.524(2), b ) 20.512(2), c ) 13.607(1) Å, ꢀ )
126.334(1)°, V ) 4615 Å3; Dc (Z ) 4) ) 1.386 g cm-3; µMo ) 1.8
mm-1; specimen: 0.55 × 0.38 × 0.24 mm; Tmin/max ) 0.74; 2θmax
) 66°; Nt ) 31846, N ) 8619 (Rint ) 0.023), No ) 6926; R )
0.034, Rw ) 0.063; T ca. 170 K.
Variata. Hydrolytic hydrogen atoms were refined in (x,y,z,Uiso).
JO801860D
Acknowledgment. We thank the Australian Research Council
for a Discovery Grant (to M.V.B. and A.H.W.) and an Australian
Postgraduate Award (to C.C.W.), the School of Biomedical,
Biomolecular and Chemical Sciences (UWA) for a summer
(29) (a) Hall, S. R., du Boulay, D. J., Olthof-Hazekamp, R., Eds. The Xtal
3.7 System; The University of Western Australia: Perth, Australia, 2001. (b)
Sheldrick, G. M. SHELXL-97. A Program for Crystal Structure Refinement;
University of Go¨ttingen: Go¨ttingen, Germany, 1997.
9352 J. Org. Chem. Vol. 73, No. 23, 2008