Efficient synthesis and host-guest properties of a new class of calix[6]azacryptands

Article abstract of DOI:10.1021/jo061616v

(Chemical Equation Presented) Two members of a new class of calix[6]azacryptands, namely, calix[6]tampo and calix[6]tamb, have been synthesized through an efficient [1 + 1] macrocyclization reaction - reduction sequence. One of them has been obtained in a

Full text of DOI:10.1021/jo061616v

at either the narrow or the wide rim of the calixarene skeleton.3
In this regard, we have developed an original class of molecular
receptors based on a calix[6]arene core rigidified by an aza-
cryptand unit.4 These calix[6]azacryptands (Figure 1) present a
hydrophobic cavity closed at the narrow rim by a nitrogenous
tripodal cap and open at the large rim for guest inclusion. These
receptors proved to be extremely versatile since they present
outstanding host-guest properties toward either charged (am-
monium or metal ions) or neutral species thanks to the aza-
cryptand cap that provides a tunable binding site.5 Indeed, this
basic cap can accommodate either metal ions or protons, offering
coordination or hydrogen bonding sites for the molecular recog-
nition processes. Recently, the calix[6]azacryptands have also
been successfully used in the intracavity chiral recognition of
neutral guests4d and in the modeling of active sites of enzymes.6
In order to develop a new class of calix[6]azacryptands possess-
ing different binding properties, we wanted to graft azacryptand
moieties bearing an aromatic ring in place of the central hetero-
atom. Here, we report on the syntheses, conformational behavior,
and preliminary host-guest properties of two new calix[6]-
azacryptands displaying this structural feature, the so-called
calix[6]tamb and calix[6]tampo.7
Efficient Synthesis and Host-Guest Properties of
a New Class of Calix[6]azacryptands
Ste´phane Le Gac, Xianshun Zeng, Camille Girardot, and
Ivan Jabin*
UniVersite´ Libre de Bruxelles, SerVice de Chimie Organique,
AVenue F. D. RooseVelt 50, CP160/06, B-1050 Brussels,
Belgium
ijabin@ulb.ac.be
ReceiVed August 3, 2006
Either linear or convergent strategies have been used for the
syntheses of the previously reported calix[6]azacryptands.4 For
the grafting of tripodal caps displaying a central aromatic ring,
we decided to apply a convergent route with a [1 + 1] macro-
cyclization reaction as the key step. Calix[6]trisamine 4 and
trisaldehydes 2 and 3 were chosen as the tripodal partners for
the macrocyclization reaction since the formation of a calix[6]-
trisimine had already proven to be efficient with compound 4.4c
First, trisaldehydes 2 and 3 were prepared in one step from
1,3,5-tris(bromomethyl)benzene 1 (Scheme 1).8 The reaction of
2-hydroxybenzaldehyde with 1 in the presence of NaOH led to
compound 2 in high yield.9 Suzuki cross-coupling reaction of
1 and 3.3 equiv of 2-formylphenylboronic acid, in presence of
a catalytic amount of Pd(PPh3)4, led to trisaldehyde 3 in 44%
yield. The average 76% yield per coupling reaction corresponds
to what is classically obtained with a benzyl halide as the starting
material.10
Two members of a new class of calix[6]azacryptands,
namely, calix[6]tampo and calix[6]tamb, have been synthe-
sized through an efficient [1 + 1] macrocyclization reaction-
reduction sequence. One of them has been obtained in a
remarkably high overall yield from the known X6H3Me3. In
comparison to all the other calix[6]azacryptands, they possess
unique conformational properties since they present a rigidi-
fied cone conformation with a partial filling of the cavity
by the methoxy groups. In contrast to calix[6]tampo, the fully
protonated derivative of calix[6]tamb behaves as a remark-
able molecular receptor toward polar neutral guests. NMR
studies have shown that the intracavity binding process is
governed by a conformational flip of the aromatic walls of
the calixarene core.
The synthesis of calix[6]trisamine 411 from the C3V sym-
metrical tris-O-methylated tert-butylcalix[6]arene (namely, X6H3-
(3) (a) Lu¨ning, U.; Lo¨ffler, F.; Eggert, J. In Calixarene 2001; Asfari, Z.,
Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2001; pp
71-88. (b) Chen, Y.; Gong, S. J. Incl. Phenom. Macrocycl. Chem. 2003,
45, 165.
(4) (a) Jabin, I.; Reinaud, O. J. Org. Chem. 2003, 68, 3416. (b) Darbost,
U.; Giorgi, M.; Reinaud, O.; Jabin, I. J. Org. Chem. 2004, 69, 4879. (c)
Zeng, X.; Hucher, N.; Reinaud, O.; Jabin, I. J. Org. Chem. 2004, 69, 6886.
(d) Garrier, E.; Le Gac, S.; Jabin, I. Tetrahedron: Asymmetry 2005, 16,
3767. (e) Le Gac, S.; Zeng, X.; Reinaud, O.; Jabin, I. J. Org. Chem. 2005,
70, 1204. (f) Zeng, X.; Coquie`re, D.; Alenda, A.; Garrier, E.; Prange´, T.;
Li, Y.; Reinaud, O.; Jabin, I. Chem. Eur. J. 2006, 12, 6393.
(5) (a) Darbost, U.; Zeng, X.; Rager, M.-N.; Giorgi, M.; Jabin, I.;
Reinaud, O. Eur. J. Inorg. Chem. 2004, 4371. (b) Darbost, U.; Rager, M.-
N.; Petit, S.; Jabin, I.; Reinaud, O. J. Am. Chem. Soc. 2005, 127, 8517.
(6) (a) Reinaud, O.; Le Mest, Y.; Jabin, I. In Calixarenes in the
Nanoworld; Vicens, J., Harrowfield, J., Eds.; Springer-Verlag: Berlin, 2006;
Chapter 13. (b) Izzet, G.; Douziech, B.; Prange´, T.; Tomas, A.; Jabin, I.;
Le Mest, Y.; Reinaud, O. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 6831.
(7) Tampo and tamb are related to 1,3,5-tris(2-(aminomethyl)phenoxy-
methyl)benzene and 1,3,5-tris(2-(aminomethyl)benzyl)benzene, respectively.
(8) 1,3,5-Tris(bromomethyl)benzene 1 was prepared from trimethyl 1,3,5-
benzenetricarboxylate according to the literature: Houk, J.; Whitesides, G.
M. J. Am. Chem. Soc. 1987, 109, 6825.
Readily available calixarenes have emerged as very attractive
platforms for the design of efficient molecular receptors toward
charged or neutral species.1 In particular, the size of the
hydrophobic cavity of calix[6]arenes is well adapted for the
inclusion of organic guests. However, these flexible macrocycles
have to be constrained in a cone conformation in order to display
intracavity host properties.2 To remedy this problem, a possible
strategy consists of introducing intramolecular covalent bridges
* To whom correspondence should be addressed. Tel: +32 2 650 35 37.
Fax: +32 2 650 27 98.
(1) (a) Gutsche, C. D. In Calixarenes ReVisited, Monographs in Supra-
molecular Chemistry; Stoddart, J. F., Ed.; The Royal Society of Chemis-
try: Cambridge, U.K., 1998. (b) Mandolini, L.; Ungaro, R. Calixarenes in
Action; Imperial College Press: London, 2000.
(2) Ikeda, A.; Shinkai, S. Chem. ReV. 1997, 97, 1713.
10.1021/jo061616v CCC: $33.50 © 2006 American Chemical Society
Published on Web 11/03/2006
J. Org. Chem. 2006, 71, 9233-9236
9233

leading to the corresponding calix[6]tampo 6 and calix[6]tamb
9. It is noteworthy that pure final calix[6]azacryptand 9 was
isolated in a remarkably high 93% overall yield from 4 (74%
overall yield from X6H3Me3), and thus this new calix[6]-
azacryptand constitutes a leading example of easily accessible
covalently bridged calix[6]arene. As expected, besides the major
calix[6]tampo 6, a minor unidentified calixarene-type species
was observed through NMR analysis of the crude reaction
mixture. As a consequence, a two-step purification sequence
was necessary to isolate pure calix[6]tampo 6. First, the amino
groups of 6 were converted into the corresponding tert-butyl
carbamate, and the obtained tris-protected calixarene 713 was
purified through column chromatography on silica gel (27%
overall yield from 4). Treatment of compound 7 with trifluoro-
acetic acid (TFA) afforded pure calix[6]tampo 6 in 86% yield.
The two new calix[6]azacryptands 6 and 9 were characterized
FIGURE 1. The calix[6]azacryptands.4
1
by H NMR spectroscopy in CDCl3 (see Figure 2a,b), and all
SCHEME 1. Syntheses of the Trisaldehydes 2 and 3a
the signals were attributed through 2D NMR analyses (COSY,
HMQC, HMBC). These NMR studies afforded several interest-
ing data on the conformational properties of these two com-
pounds:
(i) Their spectrum recorded at 293 K is characteristic of a
major C3V-symmetrical flattened cone conformation (∆δtBu
)
0.66 and 0.60 ppm for 6 and 9, respectively) with the OMe
groups directed toward the inside of the cavity (δOMe ) 1.61
and 2.10 ppm for 6 and 9, respectively).
(ii) HMBC experiments showed that the aromatic units of
the anisole moieties present the more downfield shifted reso-
nances, indicating that they are in an out position, while those
linked to the azacryptand cap are in an in position (see the
structures displayed Figure 2).
a Conditions: (i) NaOH, EtOH, reflux, 88%;9 (ii) Na2CO3, Pd(PPh3)4,
toluene/H2O, 90 °C, 44%.
Me3) was already reported by us in a two-step sequence, but in
order to avoid delicate chromatographic separation of the
intermediate, we decided to develop a new route. Thus, 4 was
prepared in an efficient three-step sequence by per-alkylation
of X6H3Me3 with ethylbromoacetate in presence of a strong base
(NaH),12 reaction with ammonia in MeOH, and subsequent
reduction of the obtained amide groups by BH3/THF (79%
overall yield). The [1 + 1] macrocyclization reactions between
calix[6]trisamine 4 and either 2 or 3 were carried out under
classical conditions (Scheme 2). 1H NMR analyses of the crude
reaction mixtures revealed the presence of the expected calix-
[6]trisimine 8 as the exclusive species, while an unidentified
minor calixarene-type species was formed along with the desired
(iii) The methylenic ArCH2 protons display well-defined
doublets even at 330 K, indicating an inhibition of the cone-
cone inversion thanks to the capping by the azacryptand units.
These conformational features differ from those observed with
the previously described calix[6]azacryptands,4 which all display
a major cone conformation with the OMe groups projected
toward the outside of the cavity. This original conformational
behavior of 6 and 9 may be due to the very different geometry
of their cap. Indeed, the central aromatic ring projects the amino
arms far away from the C3V axis, allowing the partial inclusion
of the OMe groups, which should be stabilized through CH-π
interactions with the aromatic rings of the calixarene core.
In the case of calix[6]tren and calix[6]PN3, it was shown that
the full protonation of the azacryptand unit provides a poly-
cationic binding site that can strongly interact with polar neutral
molecules, such as ureas, amides, alcohols, sulfoxides, and
nitriles.4d,5b With such polarized receptors, the guests are
stabilized inside the hydrophobic cavity through hydrogen
bonding, charge-dipole, and CH-π interactions. Similar host
properties have been even evidenced with calix[6]arenes lacking
the covalent bridges between the ammonium arms.14 Thus, we
decided to investigate the behavior of the fully protonated calix-
1
calix[6]trisimine 5 (see the Supporting Information for the H
NMR spectra of crude 5 and 8). It shows that the trisaldehyde
3 displays a perfect complementarity from a geometrical point
of view with the calix[6]arene framework. The calix[6]trisimines
5 and 8 were not isolated and directly reduced with NaBH4,
(9) The synthesis of trisaldehyde 2 was reported earlier in 85% yield
with a quasi-similar synthetic procedure (3 h of reflux instead of 20 h in
our case): Chand, D. K.; Bharadwaj, P. K. Tetrahedron Lett. 1996, 37,
8443. Complementary characterization data for compound 2: 13C NMR
(75 MHz, CDCl3) δ 58.5 (CH2), 113.0 (CH), 121.3 (CH), 125.2 (C), 125.8
(CH), 128.8 (CH), 136.0 (CH), 137.5 (C), 160.7 (C), 189.5 (CH).
(10) (a) Miyaura, N.; Yano, T.; Suzuki, A. Tetrahedron Lett. 1980, 21,
2865. (b) Sharp, M. J.; Snieckus, V. Tetrahedron Lett. 1985, 26, 5997. (c)
Maddaford, S. P.; Keay, B. A. J. Org. Chem. 1994, 59, 6501. (d) Juteau,
H.; Gareau, Y.; Labelle, M.; Sturino, C. F.; Sawyer, N.; Tremblay, N.;
Lamontagne, S.; Carrie`re, M.-C.; Denis, D.; Metters, K. M. Bioorg. Med.
Chem. 2001, 9, 1977.
(13) Similarly to the closely related triscarbamate of calix[6]PN3,4c
7
displayed dissymmetrical 1H and 13C NMR patterns. However, when the
1H NMR spectrum was recorded at high T (353 K in toluene-d8) a C3V-
symmetrical profile was observed (see the Supporting Information). The
loss of symmetry may be related to a different Z/E stereochemistry adopted
by one of the Boc groups compared to the other two.
(11) For the spectroscopic characterization of 4, see ref 4b.
(14) (a) Darbost, U.; Zeng, X.; Giorgi, M.; Jabin, I. J. Org. Chem. 2005,
70, 10552. (b) Darbost, U.; Giorgi, M.; Hucher, N.; Jabin, I.; Reinaud, O.
Supramol. Chem. 2005, 17, 243. (c) Le Gac, S.; Marrot, J.; Reinaud, O.;
Jabin, I. Angew. Chem., Int. Ed. 2006, 45, 3123.
(12) The calix[6]trisester was obtained in 96% yield from X6H3Me3
according to a previously described procedure. See: Takeshita, M.; Shinkai,
S. Chem. Lett. 1994, 1349.
9234 J. Org. Chem., Vol. 71, No. 24, 2006

FIGURE 2. 1H NMR spectra (300 MHz, CDCl3) of (a) calix[6]tampo 6; (b) calix[6]tamb 9; (c) host-guest complex 9.3H+⊃IMI obtained after
addition of TFA (6 equiv) and IMI (24 equiv) to calix[6]tamb 9. Solvent and water have been labeled “S” and “W”, respectively. The H atoms of
the included IMI have been omitted for clarity in the structure of the complex 9.3H+⊃IMI.
SCHEME 2. Syntheses of the Calix[6]azacryptands 6 and 9a
a Conditions: (i) BrCH2COOEt, NaH, THF, reflux;12 NH3, MeOH, 55 °C; BH3/THF, reflux, then EtOH, reflux, 79% (overall yield from X6H3Me3); (ii)
2, CH2Cl2, rt; (iii) NaBH4, EtOH/CH2Cl2, 0 °C then rt; (iv) Boc2O, Et3N, CH2Cl2, rt, 27% (overall yield from 4); (v) TFA, CH2Cl2, rt, 86%; (vi) 3, CH2Cl2,
rt; (vii) NaBH4, EtOH/CH2Cl2, 0 °C then rt, 93% (overall yield from 4); (viii) TFA, G, CDCl3 (with G ) polar neutral guest such as IMI, PYR, or DMSO).
[6]tampo 6.3H+ and calix[6]tamb 9.3H+ toward polar neutral
guests. Our aim was to study the ability of calix[6]tampo 6 and
calix[6]tamb 9 to accommodate a guest inside the hydrophobic
cavity despite its partial filling by the methoxy groups. Addition
of an excess of TFA (>6 equiv) to a CDCl3 solution of either
6 or 9 led to the corresponding trisammonium salts 6.3H+ and
9.3H+, respectively. Evidence of the tris-protonation was
observed on their 1H NMR spectra which display a C3V-
symmetrical profile with a downfield shift of the CH2N signals
and the presence of a broad singlet at ca. 9.0 ppm integrating
of the cavity with even more high-field-shifted resonances
than that for the corresponding free amines (i.e., δOMe ) 1.59
and 1.89 ppm for 6.3H+ and 9.3H+, respectively). Endo-
complexation of imidazolidin-2-one (IMI), pyrrolidin-2-one
(PYD), and DMSO was then tested since these polar neutral
molecules led to a remarkably strong binding with all the
previously described polyammonium calix[6]arene-based recep-
tors.4d,14 First, the NMR pattern of 6.3H+ was not affected by
the addition of a large excess of these molecules (up to 50
equiv), showing that this polycationic calixarene is unable to
host neutral guests. In strong contrast, the addition of IMI (24
equiv) to 9.3H+ gave rise to the endo-complex 9.3H+⊃IMI as
+
for six protons and corresponding to the NH2 resonance. In
both cases, the OMe groups were still directed toward the inside
J. Org. Chem, Vol. 71, No. 24, 2006 9235

TABLE 1. Relative Affinities of the Neutral Guests G toward Host
9.3H+ and NMR Complexation Induced Upfield Shifts (CIS)
Observed upon Their Endo-Complexation (Solvent: CDCl3)
related to the different geometry of the cap. Very interestingly,
host-guest NMR studies revealed that the fully protonated
derivative 9.3H+ can perform endo-complexation of polar
neutral guests that can induce a conformational flip of the
aromatic walls of the calixarene core and thus the expulsion of
the OMe groups from the cavity. In contrast, the fully protonated
derivative 6.3H+, which possesses a more flexible cap, is not
able to produce such an induced fit process. These results
highlight that a small structural change in the cap can greatly
influence the host-guest properties of the receptor. We are now
investigating the binding properties of these calix[6]azacryptands
toward charged species, such as ammonium and metal ions.
CISb (ppm)
relative
entry
G
affinitya
R
â
γ
1
2
3
DMSO
PYD
IMI
0.0005
0.02
1
-2.49
-0.98
-3.21, -3.44c
-3.31
a Relative affinity calculated at 293 K and defined as [Gin]/[IMIin] ×
[IMIfree]/[Gfree], where index “in” stands for “included”. Errors estimated
(10%. b CIS calculated at 293 K and defined as ∆δ ) δ(complexed L) -
δ(free L); R, â, and γ refer to the relative position of the protons to the
oxygen atom. c Values determined for CH2CH2CH2 and CH2N, respectively.
Experimental Section
Protected Calix[6]tampo 7. A solution of calix[6]trisamine 4
(300 mg, 0.262 mmol) and 1,3,5-tri(2′-formylphenoxymethyl)-
benzene 2 (126 mg, 0.262 mmol) in anhydrous CH2Cl2 (12 mL)
was stirred at rt for 14 h. After concentration, a 1H NMR spectrum
(CDCl3) of the resulting solid (410 mg) showed the presence of
the calix[6]trisimine 5 as the major species. A part of this crude
compound 5 (320 mg) was dissolved in a 3:1 EtOH/CH2Cl2 mixture
(30 mL), and then NaBH4 (220 mg, 5.82 mmol) was added by small
portions at 0 °C. The reaction mixture was stirred for 3 h at rt and
then concentrated. The resulting residue was dissolved in CH2Cl2
(50 mL) and washed with an aqueous HCl solution (1 M, 20 mL).
The aqueous layer was extracted with CH2Cl2 (2 × 20 mL), and
the combined organic layers were washed with an aqueous NaOH
solution (1 M, 50 mL). The aqueous layer was extracted with CH2-
Cl2 (2 × 20 mL), and the combined organic layers were washed
with water (2 × 20 mL). After concentration, the resulting residue
was dissolved in anhydrous CH2Cl2 (20 mL), and NEt3 (113 µL,
0.813 mmol) and Boc2O (178 mg, 0.816 mmol) were added
subsequently. The reaction mixture was stirred for 15 h at rt, and
then the solvent was removed. The residue was purified by column
chromatography (CH2Cl2/AcOEt, 98:2), yielding compound 7 (105
mg, 27% overall yield from 4) as a white solid.
Calix[6]tampo 6. Trifluoroacetic acid (0.5 mL, 6.5 mmol) was
added to a solution of calix[6]arene 7 (100 mg, 0.0533 mmol) in
anhydrous CH2Cl2 (1 mL). The reaction mixture was stirred for
4 h at rt and then concentrated. The resulting residue was dissolved
in CH2Cl2 (20 mL) and washed vigorously with an aqueous NaOH
solution (1 M, 15 mL) for 30 min. The aqueous layer was extracted
with CH2Cl2 (2 × 5 mL), and the combined organic layers were
washed with water (3 × 5 mL). Removal of the solvent led to pure
calix[6]tampo 6 (72 mg, 86%) as a white solid.
Calix[6]tamb 9. A solution of calix[6]trisamine 4 (650 mg, 0.568
mmol) and 1,3,5-tri(2′-formylbenzyl)benzene 3 (245 mg, 0.568
mmol) in anhydrous CH2Cl2 (30 mL) was stirred at rt for 21 h.
After concentration, a 1H NMR spectrum (CDCl3) of the resulting
solid (870 mg) showed the presence of the calix[6]trisimine 8 as
the exclusive species. A part of this crude compound 8 (850 mg)
was dissolved in anhydrous CH2Cl2 (10 mL) and then slowly added
at 0 °C to a solution of NaBH4 (633 mg, 16.74 mmol) in anhydrous
EtOH (45 mL). The reaction mixture was stirred for 1 h at 0 °C
and then 2 h at rt, and the solvent was removed. CH2Cl2 (5 mL)
was added to the resulting residue, and the salts were removed by
suction filtration and then washed with CH2Cl2 (3 × 2 mL). CH2Cl2
(80 mL) was added to the filtrate, and the organic layer was washed
with water (2 × 10 mL). Concentration led to pure calix[6]tamb 9
(794 mg, 93% overall yield from 4) as a white solid.
attested by the high-field resonance at 0.24 ppm, which
corresponds to the methylenic protons of the guest in the heart
of the cavity (Figure 2c).15 Moreover, major changes were
observed in the NMR profile of the calixarene host 9.3H+: (i)
the OMe groups experienced an impressive downfield shift
presenting a quasi-normal resonance at 3.76 ppm, showing that
they were expulsed from the cavity; (ii) signals of both CH2N
protons were high-field-shifted, indicating a shorter distance
from the C3V axis as a consequence of the establishment of H
+
bonds between the NH2 and the carbonyl group of the guest.
In addition, HMBC spectrum of the host-guest adduct
9.3H+⊃IMI showed an in position of the ArH protons of the
anisole units, denoting a conformational flip of the aromatic
walls of the calixarene core (Scheme 2). These results highlight
the remarkable ability of 9.3H+ to undergo a deep structural
reorganization induced by the complexation of a guest. Similar
results were obtained when DMSO or PYD was used instead
of IMI. It is noteworthy that, at room temperature, the in and
out exchange process of all these guests within the cavity of
9.3H+ was slower than the NMR time scale. Moreover, the
observed NMR upfield CISs (complexation induced shifts)
(Table 1) were close to those observed with the parent chiral
calix[6]tren receptor, indicating that the guests adopt a similar
positioning inside the cavity.4d Finally, NMR competitive
binding experiments allowed us to determine the relative affin-
ities of the neutral guests toward host 9.3H+ (Table 1; see the
Supporting Information). Similarly to the closely related poly-
cationic calixarene-based receptors, IMI displayed the highest
relative affinity (entry 3) since this urea combines a size well-
adapted to the calixarene cavity, a high dipole moment, and
ideally located donor and acceptor hydrogen bonding groups.
In conclusion, two members of a new class of calix[6]-
azacryptands, calix[6]tampo 6 and calix[6]tamb 9, have been
synthesized in a few steps from the 1,3,5-tris-O-methylated tBu-
calix[6]arene (X6H3Me3). One of them, calix[6]tamb 9, has been
obtained through a remarkably efficient [1 + 1] macrocycliza-
tion reaction-reduction sequence. Starting from X6H3Me3, the
overall yield of the synthesis of 9 is 74%, thus allowing a large-
scale preparation. NMR studies of these novel calix[6]-
azacryptands have shown that they display unique conforma-
tional properties since they present a rigidified cone conformation
with the methoxy groups directed toward the inside of the cavity.
Such a positioning of the OMe groups contrasts with what was
observed with all the other calix[6]azacryptands and is clearly
Acknowledgment. Part of this work was supported by the
French Ministry of Research.
Supporting Information Available: Full experimental details
spectroscopic data and NMR spectra for all new compounds
synthesized. This material is available free of charge via the Internet
at http://pubs.acs.org.
(15) The resonance at 0.24 ppm was unambiguously attributed to the
included IMI through a 2D NOESY experiment (see the Supporting
Information). Similarly, the NH resonance of the included IMI was identified
at 4.62 ppm. Moreover, HMQC spectrum allowed us to determine the
methylenic carbon resonance of the included IMI at 38.3 ppm.
JO061616V
9236 J. Org. Chem., Vol. 71, No. 24, 2006