Synthesis, structure, and conformation of aza[1n]metacyclophanes

Article abstract of DOI:10.1021/jo702151n

(Chemical Equation Presented) N-Benzyl substituted aza[1 _n]metacyclophanes (n = 4, 6, 8, and 10) were prepared in overall 40% isolated yields via Pd-catalyzed aminations. Analyses of the reaction mixtures showed that aza[1₄]metacyclo

Full text of DOI:10.1021/jo702151n

Synthesis, Structure, and Conformation of Aza[1n]metacyclophanes
Matthew Vale,† Maren Pink,‡ Suchada Rajca,† and Andrzej Rajca*,†
Department of Chemistry, UniVersity of Nebraska, Lincoln, Nebraska 68588-0304, and IUMSC,
Department of Chemistry, Indiana UniVersity, Bloomington, Indiana 47405-7102
arajca1@unl.edu
ReceiVed October 3, 2007
N-Benzyl substituted aza[1n]metacyclophanes (n ) 4, 6, 8, and 10) were prepared in overall 40% isolated
yields via Pd-catalyzed aminations. Analyses of the reaction mixtures showed that aza[14]metacyclophane
and the related polymer were the primary products (∼60% overall yield); aza[1n]metacyclophanes up to
n ) 14 and linear oligomers with up to 20 nitrogen atoms (with at least three types of end groups) were
detected. Macrocyclic structures for n ) 4, 6, and 10 were confirmed by X-ray crystallography. 1,3-
Alternate (D2d) and 1,3,5-alternate (S6) conformations in solution on NMR time scale at low temperatures
were found for macrocycles with n ) 4 and n ) 6, respectively; the barrier for ring inversion was
considerably lower for the larger macrocycle.
Introduction
opportunity to fine-tune the binding properties as a result of
the distinct conformations, due to ring sizes and bond angles
of the bridging atoms, as well as the binding properties of the
heteroatoms. However, because of difficult synthesis, only a
few heteroatom-bridged calix[n]arenes are known.5,6
With our recent success in the design and synthesis of [14]-
metacyclophane-based very high-spin molecules and polymers,7-10
including the polyarylmethyl polymer with magnetic ordering,11
we considered aza[1n]metacyclophanes (azacalix[n]arenes) as
building blocks for robust high-spin polyradicals, in which the
highly reactive carbon-centered radicals are replaced with
nitrogen-centered radicals.
[1n]Metacyclophanes (calix[n]arenes) and their derivatives
have been widely used for the complexation of molecules and
ions, gas inclusion in the solid state, scaffolds for control of
dipolar interactions, as well as scaffolds for multivalent ligands
and other biomedical and materials applications.1-4 The het-
eroatom-bridged [1n]metacyclophanes, in which the methylene
bridges are replaced by heteroatoms such as sulfur, silicon,
oxygen, phosphorus, and nitrogen, have recently attracted much
interest. Such heteroatom-bridged macrocycles provide an
* Corresponding author. Fax: (402) 472-9402.
† University of Nebraska.
‡ Indiana University.
(5) Morohashi, N.; Narumi, F.; Iki, N.; Hattori, T.; Miyano, S. Chem.
ReV. 2006, 106, 5291-5316.
(6) Ko¨nig, B.; Fonseca, M. H. Eur. J. Inorg. Chem. 2000, 2303-2310.
(7) Rajca, A.; Rajca, S.; Desai, S. R. J. Am. Chem. Soc. 1995, 117, 806-
816.
(1) (a) Biros, S. M.; Rebek, J., Jr. Chem. Soc. ReV. 2007, 36, 93-104.
(b) Bogdan, A.; Rudzevich, Y.; Vysotsky, M. O.; Boehmer, V. Chem.
Commun. 2006, 2941-2952.
(2) (a) Dalgarno, S. J.; Thallapally, P. K.; Barbour, L. J.; Atwood, J. L.
Chem. Soc. ReV. 2007, 36, 236-245. (b) Ripmeester, J. A.; Enright, G. D.;
Ratcliffe, C. I.; Udachin, K. A.; Moudrakovski, I. L. Chem. Commun. 2006,
4986-4996.
(8) Rajca, S.; Rajca, A.; Wongsriratanakul, J.; Butler, P.; Choi, S. J.
Am. Chem. Soc. 2004, 126, 6972-6986.
(9) Rajca, A.; Wongsriratanakul, J.; Rajca, S. J. Am. Chem. Soc. 2004,
126, 6608-6626.
(3) Biomedical applications of calixarenes: (a) Baldini, L.; Casnati, A.;
Sansone, F.; Ungaro, R. Chem. Soc. ReV. 2007, 36, 254-266. (b) Perret,
F.; Lazar, A. N.; Coleman, A. W. Chem. Commun. 2006, 2425-2438. (c)
da Silva, E.; Lazar, A. N.; Coleman, A. W. J. Drug DeliVery Sci. Technol.
2004, 14, 3-20.
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Eur. J. 2004, 10, 3144-3157.
(11) Rajca, A.; Wongsriratanakul, J.; Rajca, S. Science (Washington, DC,
U.S.) 2001, 294, 1503-1505.
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10.1021/jo702151n CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/06/2007
J. Org. Chem. 2008, 73, 27-35
27

Vale et al.
Aza[1n]metacyclophanes may be viewed as macrocyclic
oligomers of poly(m-aniline).12-16 Linear and star-branched
oligomers of secondary diarylamines, in which NH groups are
connected via m-phenylene units, have been studied as precur-
sors for aminyl (R2N•),17 aminium (R3N•+),18,19 and nitroxide
(R2NO•) polyradicals.20
The recent development of Pd-catalyzed aminations21,22
provides efficient synthetic routes to N-substituted aza[1n]-
metacyclophanes (N(R)-bridged aza[1n]metacyclophanes).23-30
However, very few aza[1n]metacyclophanes that are macrocyclic
oligomers of secondary diarylamines (N(H)-bridged aza[1n]-
metacyclophanes) have been reported.23 Although aza[14]-
metacyclophane (Figure 1) was first reported by Smith in 1963,31
recent attempts at the preparation of aza[14]metacyclophane by
Pd-catalyzed aminations resulted only in trace amounts of the
macrocycle in the reaction mixtures, and no N(H)-bridged aza-
[14]metacyclophane was isolated, even if dilute conditions were
used.23
Herein, we report the efficient synthesis of N(H)-bridged aza-
[14]metacyclophanes (Figure 2). Our synthetic route involves
N-benzyl protection of the secondary diarylamines and their
effective removal following Pd-catalyzed amination. We include
5-t-butyl substituents to provide enhanced solubility, thus
facilitating the preparation of higher aza[1n]metacyclophanes
as well as a detailed analysis of poly(m-aniline). This synthetic
approach provided aza[1n]metacyclophanes with n ) 4, 6, 8,
and 10. Aza[1n]metacyclophanes (n ) 4, 6, and 10) were
characterized by X-ray crystallography. Conformation and
dynamics for aza[1n]metacyclophanes (n ) 4 and 6) were
studied by variable temperature NMR spectroscopy.
FIGURE 1. [14]Metacyclophanes.
substituents in aza[1n]metacyclophanes in Figure 2 provide a
probe for the symmetry point groups of their conformations and
for the barriers of macrocyclic ring inversions by distinguishing
between diastereotopic and enantiotopic methylene protons with
1
variable temperature H NMR spectroscopy.
Results and Discussion
Synthesis. Two synthetic routes to aza[1n]metacyclophanes
were explored (Scheme 1). Both routes relied on the condensa-
tion of diaminobenzenes and dibromobenzenes via a C-N bond
coupling reaction, using conditions that are similar to those for
triarylamine-based azacyclophanes with alternating m- and
p-phenylenes.32,33 Low concentrations of monomers were used
to optimize the formation of macrocyclic products. The final
step to form aza[1n]metacyclophane in route A requires n CN
bond couplings, as compared to n/2 CN bond couplings in route
B. However, route A provides significantly higher yields of aza-
[1n]metacyclophanes. Condensations of 1,3-dibromobenzene 3
with benzyl-protected 1,3-diaminobenzene 4 at 1 mM concen-
trations gave more than 40% isolated yields of aza[1n]-
metacyclophanes (n ) 4, 6, 8, and 10), in addition to the
corresponding polymer 2.34 The analyses of the crude reaction
mixtures indicate that the relative content of the major aza[1n]-
metacyclophanes (n ) 4, 6, and 8) is 10:3:1 (Table S5,
Supporting Information), which approximately corresponds to
their isolated yields.
In route B, condensations of benzyl-protected 1,3-diami-
nobenzene 4 at ∼10 mM concentrations with bis(bromobenzene)
5 resulted in lower yields of aza[1n]metacyclophanes with the
relative content of 10:1 for the major aza[1n]metacyclophanes
(n ) 4 and 8).
Isolation of the aza[1n]metacyclophanes starts with filtration
of the crude reaction mixture through silica, followed by
debenzylation with Pd/C and ammonium formate, and then
separation by column chromatography on deactivated silica, to
provide 1-[N4]H, 1-[N6]H, and 1-[N8]H in 31, 9, and ∼3%
isolated yields, respectively. Because the N-benzyl substituted
diarylamines undergo deprotection readily on silica, the isolated
To our knowledge, aza[1n]metacyclophanes with n > 8, as
well as conformations and dynamics of any aza[1n]-
metacyclophanes in solution, have not been reported. N-Benzyl
(13) Spetseris, N.; Ward, R. E.; Meyer, T. Y. Macromolecules 1998,
31, 3158-3161.
(14) Goodson, F. E.; Hauck, S. I.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 7527-7539.
(15) Kanbara, T.; Miyazaki, Y.; Hasegawa, K.; Yamamoto, T. J. Polym.
Sci., Part A: Polym. Chem. 2000, 38, 4194-4199.
(16) Ito, A.; Ino, H.; Tanaka, K.; Manemoto, K.; Kato, T. J. Org. Chem.
2002, 67, 491-498.
(17) Diarylaminyl diradical: Rajca, A.; Shiraishi, K.; Pink, M.; Rajca,
S. J. Am. Chem. Soc. 2007, 129, 7232-7233.
(18) Triarylaminium polyradicals from oligomeric aniline derivatives with
alternating meta and para regiochemistry: Wienk, M. M.; Janssen, R. A. J.
J. Am. Chem. Soc. 1997, 119, 4492-4501.
(19) Triarylaminium polyradicals with phenylenevinylene linkers: Fuku-
zaki, E.; Nishide, H. J. Am. Chem. Soc. 2006, 128, 996-1001.
(20) Oka, H.; Kouno, H.; Tanaka, H. J. Mater. Chem. 2007, 17, 1209-
1215.
(21) (a) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852-860. (b) Hartwig,
J. F. Synlett 2006, 1283-1294.
(22) (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805-818. (b) Strieter, E. R.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2006, 45, 925-928.
(23) Fukushima, W.; Kanbara, T.; Yamamoto, T. Synlett 2005, 2931-
2934.
(24) Ito, A.; Ono, Y.; Tanaka, K. J. Org. Chem. 1999, 64, 8236-8241.
(25) Ishibashi, K.; Tsue, H.; Tokita, S.; Matsui, K.; Takahashi, H.;
Tamura, R. Org. Lett. 2006, 8, 5991-5994.
(26) Tsue, H.; Ishibashi, K.; Takahashi, H.; Tamura, R. Org. Lett. 2005,
7, 2165-2168.
(27) Suzuki, Y.; Yanagi, T.; Yamamoto, T. Synlett 2005, 263-266.
(28) Wang, M.-X.; Zhang, X.-H.; Zheng, Q.-Y. Angew. Chem., Int. Ed.
2004, 43, 838-842.
(32) Hauck, S. I.; Lakshmi, K. V.; Hartwig, J. F. Org. Lett. 1999, 1,
2057-2060.
(29) Miyazaki, Y.; Kanbara, T.; Yamamoto, T. Tetrahedron Lett. 2002,
43, 7945-7948.
(33) Yan, X. Z.; Pawlas, J.; Goodson, T., III; Hartwig, J. F. J. Am. Chem.
Soc. 2005, 127, 9105-9116.
(30) Takemura, H. J. Inclusion Phenom. Macrocyclic Chem. 2002, 42,
169-186.
(34) Aza[112]metacyclophane was isolated as well, but it was not fully
characterized.
(31) Smith, G. W. Nature (London, U.K.) 1963, 198, 879.
28 J. Org. Chem., Vol. 73, No. 1, 2008

Synthesis and Structure of Aza[1n]metacyclophanes
FIGURE 2. Aza[1n]metacyclophanes and corresponding polymer.
SCHEME 1. Synthesis of Aza[1n]metacyclophanes
yields (and purities) of the desired products are dependent on
the purification procedure (Supporting Information).
for monodisperse oligomers (Table S2, Supporting Information).
These results indicate that macrocycles 1-[N4]Bn and 1-[N6]-
Bn and polymer 2 are the major products for condensations by
route A.
Both macrocyclic products and crude reaction mixtures for
condensations by route A were characterized by gel permeation
chromatography with multiangle light scattering, mass spec-
trometry, NMR spectroscopy, and X-ray crystallography.
Gel Permeation Chromatography with Multiangle Light
Scattering (GPC/MALS). GPC/MALS provides an absolute
measure of weight average molecular weight (Mw) mass and a
column-dependent measure of number average molecular weight
(Mn).35 The crude reaction mixtures, obtained by route A, have
Mw ≈ 5 kDa and polydispersity indices PDI ≈ 1.7 (PDI ) Mw/
Mn). A typical chromatogram consists of a tall peak at the elution
time corresponding to aza[14]cyclophane 1-[N4]Bn, with a
shoulder coinciding with 1-[N6]Bn, and a broad, intense peak
at longer elution times. The last peak corresponds to polymer 2
and related oligomers, with a broad distribution of molecular
weights (Figure 3).
Mass Spectrometry. The crude reaction mixtures were
analyzed by both FAB MS and ESI MS. For the reaction
mixtures obtained by route A, the molecular ions corresponding
to the macrocycles with n ) 4 and n ) 6 were dominant in the
mass spectra (Figures S2A-C and S3A, Supporting Informa-
tion). Within uncertainties of the relative ionization efficiencies
in MS, this result is consistent with GPC/MALS data. The higher
resolution of the MS provides insight into the structure of
polymer 2, which is composed of both higher macrocycles and
linear oligomers.
In FAB MS, monocharged isotopic clusters for M+ ions of
macrocycles up to n ) 12 were well-resolved; the M+ ion for
n ) 14 was detected, but the isotopic pattern was not well-
resolved (Table S3 and Figure S2A-C, Supporting Information).
In addition to the macrocycles, relatively less intense molecular
ions for three series of linear oligomers, labeled as A-C (Figure
4), were detected with well-resolved isotopic patterns up to n
) 8-10.
The elution time of 1-[N4]Bn is longer than that of 1-[N6]-
Bn, reflecting the smaller hydrodynamic radius for 1-[N4]Bn,
as compared to 1-[N6]Bn. For both cyclophanes, the measured
values of Mw are within 5% of the formula masses, which is an
excellent agreement;36 also, the PDI is close to 1.00, as expected
In ESI MS, multiply charged isotopic clusters for molecular
ions of the macrocycles and of the linear oligomers A-C were
detected (Table S4 and Figure S3A, Supporting Information).
The presence of macrocycles with up to n ) 14 was established
by the M3+ cluster for n ) 14 with a well-resolved isotopic
pattern; partially resolved M2+ and M4+ clusters support this
(35) Absolute molecular weight of polyaniline by light scattering: Kolla,
H. S.; Surwade, S. P.; Zhang, X.; MacDiarmid, A. G.; Manohar, S. K. J.
Am. Chem. Soc. 2005, 127, 16770-16771.
(36) Agreement between experimental and nominal molecular weights
indicates that the elution from the GPC columns is practically complete
for 1-[N4]Bn and 1-[N6]Bn.
J. Org. Chem, Vol. 73, No. 1, 2008 29

Vale et al.
FIGURE 5. 1H NMR (600 MHz, chloroform-d) spectra for two
representative crude mixtures from the condensation reaction (route
A). The sample concentrations are ∼20 and ∼3 mg/mL in the top (LB
) -1.00 Hz and GB ) +0.60 Hz) and bottom (LB ) -0.80 Hz and
GB ) +0.60 Hz) spectra, respectively.
Crystal structures were obtained for 1-[N4]Bn and two solvent
polymorphs of 1-[N4]H.37 In each structure, the macrocyclic
ring adopts a calix[4]arene-like 1,3-alternate conformation with
an approximate S4 point group;38 in 1-[N4]H, the 1,3-alternate
conformations are relatively flattened (Figure 6).39-41 The 1,3-
alternate conformation is similar to that reported for the
N-methylated derivative of aza[14]metacyclophane in the solid
state.42 These conformations are different from the chair-like
conformations reported for [14]metacyclophane macrocycles in
the solid state.43,44
FIGURE 3. Gel permeation chromatography of aza[14]cyclophane
1-[N4]Bn, aza[16]cyclophane 1-[N6]Bn, mixture of 1-[N4]Bn and
1-[N6]Bn, and crude reaction mixture. Only plots from the refractive
index detector are shown.
In crystal structures of 1-[N6]Bn and 1-[N10]Bn, the asym-
metric unit contains half of the molecule, and no solvent is
included, even though for 1-[N10]Bn, a void of approximately
50 Å3 with no significant electron density is present. Both
molecules have an exact (crystallographic) inversion center (i).
The n ) 6 macrocycle adopts a 1,3,5-alternate confor-
mation with an approximate S6 point group of symmetry.38
For the n ) 10 macrocycle, the torsion angles along the
macrocyclic ring are similar to those for the n ) 6 macrocycle,
except for the linker arylamine units as indicated with arrows
in Figure 8.
FIGURE 4. Linear oligomers detected by FAB MS and ESI MS in
the crude reaction mixtures (route A).
assignment (Figure S3B-D, Supporting Information). The
assignments of the higher macrocycles with n ) 16 (M3+ and
M5+ clusters) and n ) 18 (M4+ cluster), based on partially
resolved isotopic patterns, are tentative. In the high mass range,
the isotopic clusters corresponding to the molecular ions for
linear oligomers A are relatively more intense than those
corresponding to the macrocycles; oligomers A with up to 20
nitrogen atoms are detectable.
(37) One of the solvent polymorph structures for 1-[N4]H, with two
molecules per asymmetric unit, is of lower quality, and it should be viewed
as a supporting structure. A brief description of this structure is provided
in the Supporting Information.
1
1H NMR Spectroscopy. The aromatic regions of H NMR
(38) Torsion angles for bis(benzylamino)benzene moieties (Figure 11),
with approximate Sn point groups of symmetry for the aza[1n]metacyclophane
macrocycles: 1-[N4]Bn, C6-C1-N1-C41 ) 154.76(15)°, C6-C5-N2-
C48 ) -98.31(18)°, C16-C11-N2-C48 ) -177.84(14)°, C16-C15-
N3-C55 ) 130.17(16)°, C26-C21-N3-C55 ) 160(4)°, C26-C25-N4-
C62 ) -102(4)°, C36-C31-N4-C62 ) -179.28(14)°, C36-C35-N1-
C41 ) 127.65(16)°; 1-[N6]Bn, C13-C8-N1-C1 ) -163.42(14)°, C13-
C12-N2-C18 ) -72.11(19)°, C30-C25-N2-C18 ) 171.88(14)°, C30-
C29-N3-C35 ) 19.9(2)°, C47-C42-N3-C35 ) -140.09(16)°, C1-
N1-C46#1-C47#1 (with symmetry operation #1: -x, -y, 1 - z) )
-65.5(2)°.
spectra of crude reaction mixtures (route A) show well-resolved
doublets and triplets (1:2, J ≈ 2 Hz) for aza[1n]metacyclophanes
(n ) 4, 6, and 8), with n ) 4 as the dominant product (Figure
5 and Table S5, Supporting Information). The resonances for
higher macrocycles, n ) 10 and 12, and the polymer coincide
within intense, broadened doublet- and triplet-like multiplets
at δ 6.62 and 6.48 ppm. Other relatively low-intensity reso-
nances were analyzed with the aid of a COSY spectrum; in the
6.2-7.2 ppm region, at least five three-proton spin systems and
two four-proton spin systems may be assigned to distinct linear
oligomers and their end groups (Figure S4A-C and Table S6,
Supporting Information). These assignments are consistent with
the presence of macrocycles and linear oligomers, series A-C,
detected by MS.
(39) Baklouti, L.; Harrowfield, J.; Pulpoka, B.; Vicens, J. Mini-ReV. Org.
Chem. 2006, 3, 355-384.
(40) Gutsche, C. D. Calixarenes ReVisited; Royal Society of Chemistry:
Cambridge, 1998; Ch. 4, pp 41-46.
(41) Rajca, A.; Mukherjee, S.; Pink, M.; Rajca, S. J. Am. Chem. Soc.
2006, 128, 13497-13507.
(42) Ito, A.; Ono, Y.; Tanaka, K. New J. Chem. 1998, 779-781.
(43) McMurry, J. E.; Phelan, J. C. Tetrahedron Lett. 1991, 32, 5655-
5658.
Crystal Structures. Structures for aza[1n]metacyclophanes
(n ) 4, 6, and 10) were determined using X-ray crystallography
(Table S1 and Figures 6 and 7).
(44) Rajca, A.; Padmakumar, R.; Smithhisler, D. J.; Desai, S. R.; Ross,
C. R.; Stezowski, J. J. J. Org. Chem. 1994, 59, 7701-7703.
30 J. Org. Chem., Vol. 73, No. 1, 2008

Synthesis and Structure of Aza[1n]metacyclophanes
FIGURE 6. Molecular structure aza[1n]metacyclophanes (n ) 4) 1-[N4]Bn and 1-[N4]H. Carbon and nitrogen atoms are depicted with thermal
ellipsoids (50% probability level). Hydrogen atoms, disorder and in 1-[N4]H incorporated solvent are omitted for clarity.
The 1,3,5-alternate conformation in 1-[N6]Bn is similar to
that found in calix[6]pyrrole derivatives.45 The conformations
found for 1-[N6]Bn and 1-[N10]Bn are different from typical
conformations reported for calix[6]arenes and calix[10]arenes
in the solid state.46,47
Variable Temperature H NMR Spectroscopy. H NMR
spectra of 1-[N4]Bn in chloroform-d at 298 K indicate the tetra-
fold symmetric molecular conformation, including the 2-fold
symmetry for all benzene rings. Notably, the resonance for the
benzylic methylene protons appears as a broad singlet. At lower
temperatures, the benzylic methylene protons become diaste-
reotopic, showing an AB-spin system with a geminal coupling
constant, |J| ) 17 Hz, and frequency difference, ∆ν ) 140 Hz
at 500 MHz (Figure 9). All other 1H resonances are unchanged,
and they too are compatible with the tetra-fold symmetric
conformation, including the two-fold symmetry for all benzene
rings, on the NMR time scale in the 215-330 K range.
Similarly, the 13C NMR spectra at 298 and 215 K with eight
resonances in the aromatic region support the proposed molec-
ular symmetry (Figure S7A,B, Supporting Information). On the
basis of the coalescence temperature, Tcoal ) 301 K, of the
benzylic methylene protons, a free energy barrier of 14.2 (
0.1 kcal mol-1 for ring inversion was estimated.48 This is in
good agreement with the enthalpy of activation ∆Hact ) 14.1
( 0.8 kcal mol-1 and the negligible entropy of activation (∆Sact
) -0.1 ( 2.7 cal mol-1 K-1), which were obtained by the line
shape analysis of 10 1H NMR spectra in the 265-330 K range
(Figure S5, Supporting Information).49 The conformational
mobility of 1-[N4]Bn is considerably lower than that of the
1
1
(45) Turner, B.; Botoshansky, M.; Eichen, Y. Angew. Chem., Int. Ed.
1998, 37, 2475-2478.
(46) Conformations for derivatives of calix[6]arenes in the solid state
were described as winged cone, pinched cone, double partial cone, distorted
1,2,3-alternate, and 1,2,4,5-alternate: (a) Gutsche, C. D. Calixarenes
ReVisited; Royal Society of Chemistry: Cambridge, 1998; Ch. 4, pp 60-
61. (b) Janssen, R. G.; van Duynhoven, J. P. M.; Verboom, W.; van
Hummel, G. J.; Harkema, S.; Reinhoudt, D. N. J. Am. Chem. Soc. 1996,
118, 3666-3675.
(47) Conformations for derivatives of calix[10]arenes in the solid state
were described as pinched cone and pleated loop: Perrin, M.; Ehlinger,
N.; Viola-Motta, L.; Lecocq, S.; Dumazet, I.; Bouoit-Montesino, S.;
Lamartine, R. J. Inclusion Phenom. Macrocyclic Chem. 2001, 39, 273-
276.
(48) (a) Rate constants at the coalescence temperatures (kcoal) are obtained
from the approximate equation for AB-systems, kcoal ) (π/21/ 2)[(∆ν2
+
1
6J2)1/2]. For other H spin systems, in which |J| is negligible as compared
to ∆ν, and for 13C NMR coalescences, the value coupling constant is set to
zero (i.e., kcoal ) (π/21/2)∆ν). Free energy barriers are estimated using the
Eyring equation, with the transmission coefficient set to one. (b) Eliel, E.
L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York,
1994; Ch. 8, pp 502-507.
(49) DNMR simulations were performed with a version of the computer
program WINDNMR (Reich, H. J. J. Chem. Educ. Software 1996, 3, 2;
http://www.chem.wisc.edu/areas/reich/plt/windnmr.htm).
J. Org. Chem, Vol. 73, No. 1, 2008 31

Vale et al.
FIGURE 7. Molecular structure of aza[1n]metacyclophanes (n ) 6 and 10) 1-[N6]Bn and 1-[N10]Bn. Carbon and nitrogen atoms are depicted
with thermal ellipsoids set at the 50% probability level. Hydrogen atoms are omitted for clarity.
FIGURE 8. Conformations of macrocyclic rings of aza[1n]metacyclophanes (n ) 4, 6, and 10) in crystalline 1-[N4]Bn, 1-[N6]Bn, and 1-[N10]Bn.
Benzyl groups and hydrogens are omitted for clarity. For n ) 10, arrows indicate linker arylamine units.
analogous calix[4]arene devoid of hydroxyl groups, for which
the free energy barrier is less than 9.5 kcal mol-1 43,50
are diastereotopic in the D2d symmetric conformation. At higher
temperatures, the average structure on the NMR time scale for
1-[N4]Bn has to possess two additional symmetry planes σV
dissecting the diagonal N-Bn moieties. In such an averaged
structure (e.g., a cone with a C4V point group), the benzylic
methylene protons are enantiotopic, thus appearing as a singlet
.
The NMR spectra of 1-[N4]Bn in chloroform-d at low
temperature support the assignment of a 1,3-alternate conforma-
tion with a D2d point group on the NMR time scale.51 The D2d
point group has two additional symmetry elements (two
symmetry planes σd), as compared to the approximate S4 point
group found in the solid state. The σd planes render the benzene
rings two-fold symmetric. The benzylic methylene protons are
not related by any element of symmetry, and therefore, they
1
in the H NMR spectra at higher temperatures.
The 1H NMR spectrum of 1-[N6]Bn in chloroform-d at 298
K indicates a hexa-fold symmetric conformation, with two-fold
symmetry for all benzene rings; all resonances including the
singlet for the benzylic methylene protons are sharp. At lower
temperatures, the singlet for the benzylic methylene protons at
4.76 ppm becomes an AB-system (|J| ) 17 Hz, ∆ν ) 71 Hz at
500 MHz, 243 K), and the aromatic doublet (|J| ) 2 Hz) at
6.559 ppm splits into two singlet-like resonances (∆ν ) 150
Hz at 500 MHz, 228 K); the coalescence temperatures were
(50) Gutsche, C. D. Calixarenes ReVisited; Royal Society of Chemistry:
Cambridge, 1998; Ch. 4, p 65.
(51) Structure of 1-[N4]Bn with the D2d point group is either a minimum
on the potential energy surface or an averaged structure on the NMR time
scale, resulting from the fast exchange between structures with S4 point
groups.
32 J. Org. Chem., Vol. 73, No. 1, 2008

Synthesis and Structure of Aza[1n]metacyclophanes
FIGURE 11. Torsion angles R and â.
dimensional 1H-1H COSY and 1H-13C HMQC spectra at 238
K confirm that the aromatic protons and carbons, which possess
coalescing resonances at higher temperatures, are associated with
a single spin system (Figure S8A,B, Supporting Information).
These results indicate that 1-[N6]Bn in chloroform-d at low
temperatures adopts a 1,3,5-alternate conformation with an S6
point group of symmetry. Thus, conformations for the n ) 6
macrocycle in solution and in the solid state are similar (Figure
8). At higher temperatures, two distinct conformational processes
with ∆Gact ≈ 11.7 ( 0.1 kcal mol-1 and ∆Gact ≈ 12.4 ( 0.1
kcal mol-1 led to averaged structures with a higher symmetry
on the NMR time scale.
1
FIGURE 9. Partial H NMR (500 MHz, chloroform-d, 269-330 K)
spectra of the benzylic methylene region in 1-[N4]Bn.
The process with lower ∆Gact, which exchanges selected
nuclei in the t-butylbenzene rings, led to the averaged structure
with three σd planes, thus rendering the benzene rings two-fold
symmetric. This process of exchanging the S6 symmetric
conformations to provide an average structure with a D3d point
group may be described as the conformational motion averaging
of two torsion angles (R and â) associated with each bis-
(benzylamino)benzene moiety of the macrocycle (Figure 11).
In the 1,3,5-alternate conformation with the S6 point group, R
and â may have different values within each moiety (R * â),
with alternating signs between the adjacent moieties. In the D3d
point group, R and â must have identical values within each
moiety (R ) â), with alternating signs between the adjacent
moieties, thus leading to two-fold symmetric benzene rings.
The process with higher ∆Gact, exchanging the benzylic
methylene protons, leads to an averaged structure with three σV
planes dissecting diagonal N-Bn moieties, thus rendering the
benzylic methylene protons enantiotopic. This process of
macrocyclic ring inversion provides an average structure on the
NMR time scale, which may correspond to a C6V symmetric
cone. The barrier for ring inversion is considerably lower for
the n ) 6 macrocycle than that for the n ) 4 macrocycle.52
Similarly, there are examples of derivatives of calix[6]arenes
that have similar structures in the solid state and in solution.46,53
Also, derivatives of calix[6]arenes possess a significantly greater
conformational mobility as compared to those of calix[4]-
arenes.53,54
FIGURE 10. Partial 1H NMR (500 MHz, chloroform-d, 228-298 K)
spectra of the benzylic methylene and aromatic regions in 1-[N6]Bn.
found at approximately 258 and 250 K, respectively (Figure
10). The line shape analyses of the resonances for the benzylic
1
methylene protons in seven H NMR spectra in the 243-298
K range provide ∆Hact ) 11.3 ( 0.9 kcal mol-1 and ∆Sact
≈
-4.4 ( 3.6 cal mol-1 K-1 (Figure S6, Supporting Informa-
tion),49 which are in good agreement with ∆Gact ≈ 12.4 ( 0.1
kcal mol-1 at Tcoal ) 258 K.48 Siginificantly lower ∆Gact
≈
11.7 ( 0.1 kcal mol-1 at Tcoal ) 250 K was obtained for the
conformational process involving aromatic protons.
Experimental Section
ESI MS. Studies were carried out on a time-of-flight mass
spectrometer. The solvent system used for all experiments was
trifluoroacetic acid (0.1-3%) in dichloromethane (HPLC grade).
The 13C NMR spectrum for 1-[N6]Bn at 298 K indicates
hexa-fold symmetry with two-fold symmetry for the benzene
rings; however, two of the eight resonances in the aromatic
region at 149.4 and ∼111 ppm were broadened; at 215 K, two
pairs of new resonances at 149.9 and 147.0 ppm (∆ν ) 365
Hz) and at 113.6 and 107.0 ppm (∆ν ) 830 Hz) were obtained.
For the first pair of resonances, Tcoal ) 260 K was reasonably
well-determined, giving ∆Gact ≈ 11.7 kcal mol-1, which is in
(52) 1H NMR spectrum for 1-[N8]Bn in chloroform-d is well-resolved,
showing a singlet for the benzylic methylene protons, in the 298-260 K
range. Also, the 13C NMR spectrum for 1-[N8]Bn in chloroform-d shows
no broadening at 298 K (Figure S11, Supporting Information). This might
suggest that the n ) 8 macrocycle might even be more conformationally
mobile than the n ) 6 macrocycle.
(53) Molins, M. A.; Nieto, P. M.; Sanchez, C.; Prados, P.; de Mendoza,
J.; Pons, M. J. Org. Chem. 1992, 57, 6924-6931.
(54) van Duynhoven, J. P. M.; Janssen, R. G.; Verboom, W.; Franken,
S. M.; Casnati, A.; Pochini, A.; Ungaro, R.; de Mendoza, J.; Nieto, P. M.;
Prados, P.; Reinhoudt, D. N. J. Am. Chem. Soc. 1994, 116, 5814-5822.
1
excellent agreement with the barrier obtained from H NMR
spectra. For the second pair of resonances, Tcoal ) 270 K, which
is within the expected range, gave a similar value of ∆Gact
(Figures S9A-F and S10, Supporting Information). Two-
J. Org. Chem, Vol. 73, No. 1, 2008 33

Vale et al.
Concentrations of samples injected were 10-5 to 10-6 M. Flow rates
(5-20 µL min-1) were controlled by a syringe pump. Samples of
isolated amines were prepared using an acidic solvent system.
Samples of crude reaction mixtures were stirred and diluted in
dichloromethane with the final dilution performed with the acidic
solvent mixture.
Debenzylation. Excess amounts of Pd/C (10% Pd wt on C) and
freshly recrystallized ammonium formate were added in two
portions to a solution of N-benzyl aza[1n]metacyclophane in ethanol
at reflux. After 4 h at reflux, filtration through Celite, preparative
TLC, and recrystallization provided N(H)-bridged aza[1n]-
metacyclophane.
Tetraazacyclophane 1-[N4]Bn. White crystals from dichlo-
romethane/methanol. Mp 206-207 °C; 1H NMR (500 MHz,
chloroform-d, 298 K): δ ) 7.304 (d, J ) 7, 8 H), 7.249 (t, J ) 8,
8 H), 7.173 (t, J ) 7, 4 H), 6.544 (d, J ) 2, 8 H), 6.397 (t, J ) 2,
GPC/MALS. A 17-angle light scattering detector and interfero-
metric refractive index detector were used for GPC/MALS studies.
Two 4.6 mm × 300 mm 5-µ GPC columns (500 Å and following
in a sequence 103 Å), with THF as the mobile phase, were used.
The flow rate of THF was 0.5 mL/min, and dn/dc was computed
on-line. Solutions of oligomer, polymer, or a crude mixture in THF
(100 µL) were injected into a 20 µL loop, typically 3 times.
X-ray Crystallography. Crystals for X-ray studies were prepared
from solutions of solvent precipitant mixtures. Data collections were
performed on a platform diffractometer equipped with a SMART
6000 detector using Mo KR radiation (graphite monochromator).
Final cell constants were calculated from the xyz centroids of strong
reflections from the actual data collection after integration (SAINT);55
intensity data were corrected for absorption (SADABS).56 Space
groups were determined based on intensity statistics and systematic
absences. Structures were solved with direct methods (SIR-92) and
refined with full-matrix least-squares/difference Fourier cycles
(SHELXL-97).57,58 All non-hydrogen atoms were refined with
anisotropic displacement parameters unless noted otherwise in the
CIF files. The hydrogen atoms were placed in ideal positions and
refined as riding atoms with relative isotropic displacement
parameters. For 1-[N4]Bn and 1-[N4]H, disorder was refined for
t-butyl groups and phenyl t-butyl groups.
Variable Temperature NMR Spectroscopy. 1H NMR (500
MHz) spectra were obtained for ∼0.01 M solutions of 1-[N4]Bn
and 1-[N6]Bn in chloroform-d. The line shape analyses were carried
out for the AB-systems of the benzylic methylene resonances in a
temperature range not too far from the coalescence temperature,
such that the values of the frequency differences for the coalescing
resonances were constant for each compound. The rate constants
(k) were numerically fit to the Eyring equation, ln(k/T) versus 1000/
T, to provide straight line fits with correlation coefficients R2 )
0.992-0.994 and values of the activation parameters. The error
bars for the enthalpy of activation and entropy of activation were
based on standard errors for the slope and intercept, which were
multiplied by a factor of 2.
1
4 H), 5.1-4.6 (d(br), 8 H), 1.107 (s, 36 H); H NMR (500 MHz,
chloroform-d, 215 K): δ ) 7.414 (d, J ) 8, 8 H), 7.342 (t, J ) 8,
8 H), 7.281 (s, residual solvent peak, CHCl3), 7.250 (t, J ) 8, 4
H), 6.685 (s, 8 H), 6.519 (s, 4 H), 5.084, 4.740 (AB, J ) 17, 8 H),
1.097 (s, 36 H); 13C NMR (125 MHz, chloroform-d, 298 K): δ )
153.5, 148.9, 140.1, 128.3, 126.9, 126.5, 112.7, 111.0, 57.4, 34.8,
31.2; 13C NMR (125 MHz, chloroform-d, 215 K): δ ) 153.2, 147.9,
139.8, 128.4, 126.4, 126.1, 110.9, 109.9, 57.4, 34.6, 30.9; IR (ZnSe,
cm-1): 1582 (Ar); LR-HR-FAB MS (3-NBA) cluster, m/z (ion type,
% RA for m/z 200-1100, deviation from the formula) at 949.6098
([M + 1]+, 95.5, 0.6 ppm for 13C1
C
1H7614N4), 948.6048 ([M]+,
12
67
12
100, 2.3 ppm for
C
1H7614N4).
68
Hexaazacyclophane 1-[N6]Bn. White crystals from diethyl
ether/hexane. Mp 265 °C; 1H NMR (500 MHz, chloroform-d, 298
K): δ ) 7.247 (s, residual solvent peak, CHCl3), 7.22-7.08 (m,
30 H), 6.559 (d, J ) 2, 12 H), 6.435 (t, J ) 2, 6 H), 4.758 (s, 12
1
1
H), 1.101 (s, 54 H); H NMR (500 MHz, chloroform-d, H-1H
COSY cross-peak, 238 K): δ ) 7.303 (d, J ) 7, 12 H, 7.244),
7.273 (s, residual solvent peak of CHCl3), 7.244 (t, J ) 7, 12 H,
7.303, 7.182), 7.182 (t, J ) 7, 6 H, 7.244), 6.733 (s, 6 H, 6.440,
6.405), 6.440 (s, 6 H, 6.733, 6.405), 6.405 (s, 6 H, 6,733, 6.440),
4.874, 4.724 (AB, J ) 17, 12 H, 4.874, 4.724), 1.120 (s, 54 H); 1H
NMR (500 MHz, chloroform-d, 228 K): δ ) 7.304 (d, J ) 7.5,
12 H), 7.277 (s, residual solvent peak of CHCl3), 7.246 (t, J ) 7.5,
12 H), 7.184 (t, J ) 7.5, 6 H), 6.734 (s, 6 H), 6.439 (s, 6 H), 6.404
(s, 6 H), 4.88, 4.72 (AB, J ) 17, 12 H), 1.120 (s, 54 H); 1H NMR
(500 MHz, chloroform-d, 215 K): δ ) 7.324 (d, J ) 7.5, 12 H),
7.267 (t, J ) 7.5, 12 H), 7.198 (t, J ) 7.5, 6 H), 6.759 (s, 6 H),
6.434 (s, 6 H), 6.391 (s, 6 H), 4.888, 4.719 (AB, J ) 17, 12 H),
1.125 (s, 54 H); 13C NMR (125 MHz, chloroform-d, 298 K): δ )
153.2, 149.4 (br), 140.4, 128.3, 126.43, 126.40, ∼111 (v. br), 110.7,
57.1, 34.8, 31.2; 13C NMR (125 MHz, chloroform-d, 1H-13C
HMQC cross-peak, 238 K): δ ) 152.4 (q), 149.9 (br, q), 147.1
(br, q), 139.7 (q), 128.3 (7.246), 126.3 (7.182), 126.0 (7.703), 113.5
(br, 6.733), 109.9 (6.405), 107.3 (br, 6.440), 56.8 (4.874, 4.724),
34.7 (q), 31.0 (1.120); 13C NMR (125 MHz, chloroform-d, 215
K): δ ) 152.3, 149.9, 147.0, 149.6, 128.3, 126.3, 125.9, 113.6,
109.7, 107.0, 56.7, 34.6, 31.0; IR (ZnSe, cm-1): 1578 (Ar); LR-
HR-FAB MS (3-NBA) cluster, m/z (ion type, % RA for m/z 200-
General Procedure. Route A. A 0.001 M solution of diamine
4 (1 equiv) in toluene, containing 5-t-butyl-1,3-dibromobenzene 3
(1.1 equiv), Pd(dba)2 (0.05 equiv), t-BuONa (3 equiv), and P(t-
Bu)3 (0.04 equiv), was stirred in a closed Schlenk vessel under
nitrogen at room temperature. The reaction mixture was periodically
monitored by TLC and 1H NMR spectroscopy to follow the
formation of products. After about 9 days at room temperature,
2050, deviation from the formula) at 1423.9160 ([M + 1]+, 100,
1
the crude reaction mixtures were analyzed by H NMR spectros-
12
-1.5 ppm for 13C1
C
1H11414N6), 1422.9105 ([M]+, 97, 0.0 ppm
101
copy, MS, and GPC, and the macrocyclic products were separated
by column chromatography and/or preparative TLC. In an alterna-
tive procedure, the crude reaction mixture was filtered through silica,
subjected to debenzylation, and then separated by chromatography.
Route B. A 0.01 M solution of diamine 4 (1 equiv) in toluene,
containing bis(bromobenzene) 5 (1.1 equiv), Pd(OAc)2 (0.08 equiv),
t-BuONa (3 equiv), and P(t-Bu)3 (0.24 equiv), was stirred in a closed
Schlenk vessel under nitrogen at 100 °C. After 3 days at 100 °C,
the crude reaction mixtures were analyzed by 1H NMR spectroscopy
and FAB MS, and the macrocyclic products were separated by
column chromatography and/or preparative TLC.
for
C
1H11414N6).
12
102
Octaazacyclophane 1-[N8]Bn. White solid from benzene/
methanol. Complicated melting behavior was found: 90-95 °C
(white solid forms a colorless treacle), 113-115 °C (glass-like
1
softening), and 221-228 °C (viscous oil); H NMR (500 MHz,
chloroform-d, 298 K): δ ) 7.134-7.125 (m, 32 H), 7.095-7.050
(m, 8 H), 6.590 (d, J ) 2, 16 H), 6.502 (t, J ) 2, 8 H), 4.695 (s,
1
16 H), 1.072 (s, 72 H); H NMR (500 MHz, chloroform-d, 260
K): δ ) 7.162-7.124 (m, 32 H), 7.090-7.050 (m, 8 H), 6.584 (d,
J ) 2, 16 H), 6.485 (t, J ) 1-2, 8 H), 4.699 (s, 16 H), 1.061 (s,
72 H); 13C NMR (125 MHz, chloroform-d): δ ) 152.3, 148.7,
139.7, 128.3, 126.63, 126.40, 111.3, 110.2, 56.8, 34.8, 31.2; IR
(ZnSe, cm-1): 1575 (Ar); LR-HR-FAB MS (3-NBA) cluster, m/z
(55) SAINT 6.1; Bruker Analytical X-Ray Systems: Madison, WI, 2001.
(56) Blessing, R. SADABS. Acta Crystallogr., Sect. A: Found. Crystal-
logr. 1995, 51, 33-38.
(ion type, % RA for m/z 200-2050, deviation from the formula)
12
at 1898.2179 ([M + 1]+, 100, -0.3 ppm for 13C1
C
1H15214N8),
135
(57) Altomare, A.; Cascarno, G.; Giacovazzo, C.; Gualardi, A. SIR-92.
J. Appl. Crystallogr. 1993, 26, 343-350.
1897.2148 ([M]+, 82, 0.4 ppm for
C
1H15214N8).
12
136
Decaazacyclophane 1-[N10]Bn. White crystals from benzene/
(58) SHELXL-97; Bruker Analytical X-Ray Systems: Madison, WI,
2001.
isopropyl alcohol. Mp 205-207 °C; 1H NMR (500 MHz, chloroform-
34 J. Org. Chem., Vol. 73, No. 1, 2008

Synthesis and Structure of Aza[1n]metacyclophanes
d): δ ) 7.14-7.05 (m, 50 H), 6.609 (d, J ) 2, 20 H), 6.474 (t, J
) 2, 10 H), 4.667 (s, 20 H), 1.075 (s, 90 H); 13C NMR (125 MHz,
chloroform-d, LB ) 1, 5, 10 Hz): δ ) 152.2, 148.7, 139.7, 128.3,
126.68, 126.40, 111.5, 110.1, 56.8, 34.8, 31.3; IR (ZnSe, cm-1):
1576 (Ar); LR-HR-FAB MS (3-NBA) cluster, m/z (ion type, %
RA for m/z 550-4000, deviation from the formula) at 2372.5202
cm-1): 3390 (NH), 1585 (Ar); LR-HR-FAB MS (3-NBA) cluster,
m/z (ion type, % RA for m/z 200-1200, deviation from the formula)
12
at 883.6322 ([M + 1]+, 89, 0.0 ppm for 13C1
C
1H7814N6),
59
882.6276 ([M]+, 100, 1.3 ppm for
C
1H7814N6).
60
12
Octaazacyclophane 1-[N8]H. 3.1 mg (2.6% for two steps). 1H
NMR (500 MHz, chloroform-d): δ ) 6.623 (t, J ) 2, 8 H,), 6.606
(d, J ) 2.0, 16 H), 5.641 (s, 8 H), 1.231 (s, 72 H); IR (ZnSe, cm-1):
3384 (NH), 1582 (Ar); LR-HR-FAB MS (3-NBA) cluster, m/z
12
14
([M + 1]+, 100, 0.3 ppm for 13C1
C
1H190 N10), 2371.5132 ([M]+
169
75,-0.1ppmfor13C112C169 H189 N10 and1.8ppmfor12C170 H190 N10).
1
14
1
14
ESI MS (Figures S12A-C, Supporting Information).
(ion type, % RA for m/z 200-4000, deviation from the formula)
at 1177.8425 ([M + 1]+, 93.7, 0.7 ppm for 13C1
C
1H10414N8),
12
Dodecaazacyclophane 1-[N12]Bn. Treated with methanol twice
79
1
12
(centrifuge and decantation). H NMR (500 MHz, chloroform-d):
1176.8364 ([M]+, 100, 1.7 ppm for
C
1H10414N8).
80
δ ) 7.127 (d, J ) 4, 32 H), 7.15-7.05 (m, 60 H), 6.615 (d, J )
2, 24 H), 6.478 (t, J ) 2, 12 H), 4.664 (s, 24 H), 1.077 (s, 108 H).
ESI MS (Figures S13A-D, Supporting Information).
Tetraazacyclophane 1-[N4]H. Pale red solid, 24.0 mg (77%),
87.0 mg (83%). Mp 326-327 °C; 1H NMR (500 MHz, chloroform-
d): δ ) 7.068 (t, J ) 2, 4 H,), 6.380 (d, J ) 2, 8 H), 5.588 (s, 4
H), 1.269 (s, 36 H); 13C NMR (125 MHz, chloroform-d): δ )
154.1, 144.0, 109.3, 103.3, 34.5, 31.2; IR (ZnSe, cm-1): 3389 (NH),
1590 (Ar); LR-HR-FAB MS (3-NBA) cluster, m/z (ion type, %
Acknowledgment. This research was supported by the
National Science Foundation (CHE-0107241 and CHE-0414936).
We thank Prof. Hans J. Reich (University of Wisconsin,
Madison) for kindly providing the computer program WIND-
NMR for DNMR simulations. MS analyses were carried out at
the Nebraska Center for Mass Spectrometry. We thank Drs.
Ronald L. Cerny and Kurt Wulser for assistance with ESI MS
experiments.
RA for m/z 200-750, deviation from the formula) at 589.4230 ([M
12
+ 1]+, 76, 0.7 ppm for 13C1
C
1H5214N4), 588.4175 ([M]+, 100,
39
Supporting Information Available: Complete description of
experimental details and product characterization, including analyses
of crude reaction mixtures, dynamic NMR studies, and X-ray
crystallographic files. This material is available free of charge via
the Internet at http://pubs.acs.org.
12
2.9 ppm for
C
1H5214N4).
40
Hexaazacyclophane 1-[N6]H. Purple crystals, 7.5 mg (77%).
Mp 396-398 °C; 1H NMR (500 MHz, chloroform-d): δ ) 6.888
(t, J ) 2, 6 H,), 6.547 (d, J ) 2.0, 12 H), 5.696 (s, 6 H), 1.253 (s,
54 H); 13C NMR (125 MHz, chloroform-d): δ ) 153.6, 144.0,
142.3 (instrument artifact), 108.9, 104.8, 34.7, 31.2; IR (ZnSe,
JO702151N
J. Org. Chem, Vol. 73, No. 1, 2008 35