N-Methyl-Substituted Aza[1n]metacyclophane: Preparation, Structure, and Properties

Article abstract of DOI:10.1021/jo990983m

A series of aza[1_n]metacyclophanes (n = 3-8), which correspond to the cyclic oligomers of poly(m-aniline), are obtained in one step by a Pd(0)-catalyzed amination reaction of 3-bromo-N-methylaniline. The most stable conformations of the cyclic trimer and tetramer are determined by density functional calculations. The theoretical results show that these new macrocyclic compounds can be regarded as precursors for cyclophane-based high-spin molecules. Moreover, we describe their spectroscopic and electrochemical properties in connection with the ring size of these cyclic oligomers.

Full text of DOI:10.1021/jo990983m

8236
J . Org. Chem. 1999, 64, 8236-8241
N-Meth yl-Su bstitu ted Aza [1n ]m eta cyclop h a n e: P r ep a r a tion ,
Str u ctu r e, a n d P r op er ties
Akihiro Ito, Yukiharu Ono, and Kazuyoshi Tanaka*
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, J apan
Received J une 21, 1999
A series of aza[1n]metacyclophanes (n ) 3-8), which correspond to the cyclic oligomers of poly(m-
aniline), are obtained in one step by a Pd(0)-catalyzed amination reaction of 3-bromo-N-
methylaniline. The most stable conformations of the cyclic trimer and tetramer are determined by
density functional calculations. The theoretical results show that these new macrocyclic compounds
can be regarded as precursors for cyclophane-based high-spin molecules. Moreover, we describe
their spectroscopic and electrochemical properties in connection with the ring size of these cyclic
oligomers.
In tr od u ction
On the other hand, a molecule composed of two
building blocks, an aromatic ring and an aliphatic unit
forming a bridge between two or more positions of the
aromatic ring, is known as cyclophane.5 Many kinds of
cyclophanes have been synthesized for the purpose of
investigation of the peculiar electronic and spectroscopic
properties due to the interesting stereochemistry and,
moreover, the effective binding properties as host mol-
ecules in molecular recognition chemistry.5 In particular,
calixarenes 2, one of the [1n]metacyclophanes, are ideal
starting materials for preparation of various types of host
molecules.6 Although carbon is the common bridging
element in useful macrocyclic compounds such as por-
phyrins and calixarenes, other elements such as silicon,
nitrogen, phosphorus, oxygen, sulfur, and so forth can
be new bridging elements to give additional chemical and
physical properties. Indeed, over the past few years, a
considerable number of studies have been made on the
syntheses of various heteroatom-bridged [1n]cyclophanes.7
Preparation of the aza-bridged macrocyclic oligomers,
however, is definitely in need of efficient synthetic
methods to form carbon-nitrogen bonds. Recently, two
research groups have reported a simple catalytic method
for the conversion of aryl bromides to arylamines,8
superseding the laborious Ullmann coupling reaction.
The chemistry of high-spin organic molecules is a
topical area in connection with the exploitation of organic
ferromagnets.1 The fundamental problems of creating
organic ferromagnets are first that of selecting a spin-
bearing molecule (or a radical center) and second that of
developing strong ferromagnetic interaction between the
molecules. As is well-known, chemically and thermally
stable polyradicals often contain heteroatoms that serve
as spin-bearing sites,2 and they are connected to each
other by m-phenylene units which have proven effective
ferromagnetic couplers.1 Hence, we are interested in
macrocyclic oligomers of poly(m-aniline) 1 because of the
fascinating possibilities that the oxidized species of these
compounds show high-spin ground states.3 Furthermore,
a “closed loop” arrangement of multispin systems guar-
antees the robust ferromagnetically coupled spin
alignment.1f In fact, Rajca and co-workers have demon-
strated that calix[4]arene-based polyradicals are viable
building blocks for high-spin polyradicals.4
(5) (a) Diederich, F. Cyclophanes; Monograghs in Supramolecular
Chemistry; Royal Society of Chemistry: London, 1991. (b) Vo¨gtle, F.
Cyclophane Chemistry; Wiley: Chichester, 1993.
(6) (a) Gutsche, C. D. Calixarenes; Monographs in Supramolecular
Chemistry; Royal Society of Chemistry: London, 1989. (b) Izatt, R.
M.; Bradshaw, J . S.; Pawlak, K.; Bluening, R. L.; Tarbet, B. J . Chem.
Rev. 1992, 92, 1261. (c) Shinkai, S. Tetrahedron 1993, 49, 8933. (d)
Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713. (e) Ikeda, A.;
Shinkai, S. Chem. Rev. 1997, 97, 1713.
(1) (a) Iwamura, H. Pure Appl. Chem. 1987, 59, 1595. (b) Iwamura,
H. Adv. Phys. Org. Chem. 1990, 26, 179. (c) Dougherty, D. A. Acc.
Chem. Res. 1991, 24, 88. (d) Iwamura, H. Pure Appl. Chem. 1993, 65,
57. (e) Borden, W. T.; Iwamura, H.; Berson, J . A. Acc. Chem. Res. 1994,
24, 109. (f) Rajca, A. Chem. Rev. 1994, 94, 871.
(2) Forrester, A. R.; Hay, J . M.; Thomson, R. H. Organic Chemistry
of Stable Free Radicals; Academic Press: New York, 1968.
(3) (a) Yoshizawa, K.; Tanaka, K.; Yamabe, T. Chem. Lett. 1990,
1311. (b) Ishida, T.; Iwamura, H. Chem. Lett. 1991, 317. (c) Yoshizawa,
K.; Tanaka, K.; Yamabe, T.; Yamauchi, J . J . Chem. Phys. 1992, 96,
5516. (d) Yoshizawa, K.; Takata, K.; Tanaka, K.; Yamabe, T. Polym.
J . 1992, 24, 857. (e) Ito, A.; Yoshizawa, K.; Tanaka, K.; Yamabe, T.
Solid State Commun. 1993, 87, 935. (f) Ito, A.; Ota, K.; Tanaka, K.;
Yamabe, T.; Yoshizawa, K. Macromolecules 1995, 28, 5618. (g)
Yoshizawa, K.; Hoffmann, R. Chem. Eur. J . 1995, 1, 403. (h) Goto, H.;
Iino, K.; Akagi, K.; Shirakawa, H. Synth. Met. 1997, 85, 1683.
(4) (a) Rajca, A.; Rajca, S.; Padmakumar, R. Angew. Chem., Int. Ed.
Engl. 1994, 33, 2091. (b) Rajca, A.; Rajca, S.; Desai, S. R. J . Am. Chem.
Soc. 1995, 117, 806. (c) Rajca, A.; Lu, K.; Rajca, S. J . Am. Chem. Soc.
1997, 119, 10335. (d) Rajca, A.; Wongsriratanakul, J .; Rajca, S. J . Am.
Chem. Soc. 1997, 119, 11674. (e) Rajca, A.; Wongsriratanakul, J .; Rajca,
S.; Cerny, R. Angew. Chem., Int. Ed. Engl. 1998, 37, 1229.
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Bubenitschek, P.; J ones, P. G.; Thondorf, I. J . Org. Chem. 1995, 60,
7406. (c) Mascal, M.; Richardson, J . L.; Blake, A. J .; Li, W.-S.
Tetrahedron Lett. 1997, 38, 7639. (d) Nakayama, J .; Katano, N.;
Sugihara, Y.; Ishii, A. Chem. Lett. 1997, 897. (e) Katano, N.; Sugihara,
Y.; Ishii, A.; Nakayama, J . Bull. Chem. Soc. J pn. 1998, 71, 2695 and
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D. J . Chem. Commun. 1998, 283. (i) Baxter, I.; Colquhoun, H. M.;
Hodge, P.; Kohnke, F. H.; Williams, D. J . Chem. Commun. 1998, 1991.
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L.; Reuter, R.; Mu¨llen, K. Eur. J . Org. Chem. 1998, 555, 5.
10.1021/jo990983m CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/29/1999

N-Methyl-Substituted Aza[1n]metacyclophane
J . Org. Chem., Vol. 64, No. 22, 1999 8237
Sch em e 1
Since then, several complicated oligo- and polyarylamine
compounds have been successfully prepared on the basis
of this method.9 We have applied this method to the
preparation of aza-bridged [1n]metacyclophanes simply
using bromo-substituted N-methylanilines as a starting
material. This attempt gave an affirmative result, and
preliminarily, we have already reported on the major
product 4 with its X-ray structure.10 In the present paper,
we describe a series of N-methyl-substituted aza[1n]-
metacyclophanes 3-8 having the prototypical macrocyclic
structure of azacalix[n]arene. Furthermore, we performed
quantum chemical calculations of the N-unsubstituted
model compounds of 3 and 4 using density functional
theory (DFT). In addition, spectroscopic and electrochemi-
cal properties of the compounds 3-8 are also described
in connection with the ring size of the macrocycles.
Ch a r t 1
Ta ble 1. 1H NMR Ch em ica l Sh ifts (δ, p p m ) of
In tr a a n n u la r (HX) a n d Extr a a n n u la r (HA a n d HB)
Ar om a tic P r oton s of 3-8 a n d DMP D in CDCl3 a t 298 K
Resu lts a n d Discu ssion
Syn t h esis of Aza [1n ]m et a cyclop h a n es 3-8. N-
Methyl-substituted aza[1n]metacyclophane was synthe-
sized by Pd(0)-catalyzed amination reaction of 3-bromo-
N-methylaniline (9) in toluene (ca. 0.2 M), by following
the procedure shown in Scheme 1. As shown in our
previous report,10 this reaction afforded 4 as a white solid
in moderate yield (12.9%). It is interesting to note that
the main product is cyclic tetramer 4, taking two points
into consideration: (i) in the preparation of some cyclic
oligoarenes including calix[n]arene, the tetramer tends
to be selectively prepared, and (ii) according to the
reaction mechanism proposed by two research groups,8
the reaction proceeds via formation of an intermediate
PdII complex coordinated with both ends of a linear
oligoaniline in the last stage of the cyclization reaction.
Note that the conversion of N-methylaniline into the
N-methyldiarylamines cannot proceed by the Ullmann
coupling reaction, probably owing to poisoning of the Cu
catalyst by N-methylaniline.
δ
compd
HX
HA
HB
3
4
5
6
7
8
7.10
6.41
6.61
6.63
6.61
6.63
5.79
7.12
7.26
7.15
7.12
7.11
7.09
6.97
6.67
6.54
6.58
6.57
6.55
6.56
5.98
DMPD
Accordingly, medium-pressure liquid chromatography
(MPLC) was carried out using silica gel for isolation of
the macrocycles with different sizes (eluent: EtOAc-
Et2O (4:1)). The exact molecular masses of compounds 3
and 5-8 were determined by high-resolution mass
spectrometry, confirming their molecular formulas as
(C7H7N)n (n ) 3 and 5-8). The isolated yields of the
corresponding macrocycles 3-8 (with the exception of 4)
were 1.6, 5.6, 2.0, 3.3, and 1.3%, respectively. It should
be noted that conformation isomers are not found for the
trimer 3 in contrast to the case of the methylene-bridged
[1.1.1]metacyclophane.4b
On the other hand, the GC-MS study showed that a
fraction (Rf ) 0.45 [n-hexane:CH2Cl2 ) 1:1]) other than
the fraction containing 4 (Rf ) 0.65 [n-hexane:CH2Cl2 )
1:1]) contains a mixture of the azametacyclophanes 3-8.
In contrast to the N-methyl-substituted aza[1n]meta-
cyclophanes, we did not succeed in preparation of N-
unsubstituted ones despite many optimization experi-
ments (variation of related ligands and bases).
(8) (a) Beller, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 1316. (b)
Hartwig, J . F. Synlett 1997, 329. (c) Hartwig, J . F. Angew. Chem., Int.
Ed. Engl. 1998, 37, 2046. (d) Wolfe, J . P.; Wagaw, S.; Marcoux, J .-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (e) Hartwig, J . F. Acc.
Chem. Res. 1998, 31, 852.
(9) (a) Kambara, T.; Izumi, K.; Nakadani, Y.; Narise, T.; Hasegawa,
K. Chem. Lett. 1997, 1185. (b) Louie, J .; Hartwig, J . F.; Fry, A. J . J .
Am. Chem. Soc. 1997, 119, 11695. (c) Yang, M.-H.; Lin, T.-W.; Chou,
C.-C.; Lee, H.-C.; Chang, H.-C.; Lee, G.-H.; Leung, M.-K.; Peng, S.-M.
Chem. Commun. 1997, 2279. (d) Sadighi, J . P.; Singer, R. A.; Buchwald,
S. L. J . Am. Chem. Soc. 1998, 120, 4960. (e) Goodson, F. E.; Hartwig,
J . F. Macromolecules 1998, 31, 1700. (f) Spetseris, N.; Ward, R. E.;
Meyer, T. Y. Macromolecules 1998, 31, 3158.
1H NMR Sp ectr oscop y. The H NMR spectroscopic
1
analysis supports the metacyclophane structure of com-
pounds 3-8. The aromatic AB2X system gives rise to two
triplets and a doublet of doublets. The remaining singlet
is assigned to N-methyl protons. Table 1 lists the 1H
NMR chemical shifts of the intraannular (HX) and
extraannular (HA, HB) aromatic protons for 3-8. For
comparison, the data of N,N′-dimethyl-1,3-phenylenedi-
amine (DMPD) (Chart 1) are also added. The signal of
(10) Ito, A.; Ono, Y.; Tanaka, K. New J . Chem. 1998, 779.

8238 J . Org. Chem., Vol. 64, No. 22, 1999
Ito et al.
Ta ble 3. Cyclic Volta m m etr ic F ir st Oxid a tive P ea k
P oten tia lsa for 3-8
ox
ox
compd
E1 (V vs SCEb)
compd
E1 (V vs SCEb)
3
4
5
+0.81
+0.79
+0.72
6
7
8
+0.62
+0.62
+0.63
a
Conditions: 0.1 M n-Bu4NClO4 in CH2Cl2, potential vs Fc/
Fc+, Pt electrode, 298 K, scan rate 100 mV s-1
.
Potentials were
b
converted to SCE using the following equation: ESCE ) Eobsd(Fc/
Fc+) + 0.48.
unstable radical cation undergoing a chemical reaction
before it is oxidized into the polycationic states. As will
be described in the next section, this may be rationalized
in terms of an immediate benzidine formation reaction.
ox
Moreover, the E1 value decreases with increasing ring
size of oligomers up to the pentamer 5, and finally, the
value levels off in 6 (ca. 0.62 V vs SCE). This result is
similar to the behavior of UV-vis spectra for 3-8,
indicating that effective conjugation length reaches the
upper limit around the hexamer 6.
Th eor etica l Con sid er a tion . The molecular struc-
tures for the N-unsubstituted model compounds of 3 and
4 were optimized using the density functional theory
(DFT).11 Becke’s 1988 gradient-corrected exchange func-
tional12 together with Perdew and Wang’s 1991 gradient-
corrected correlation functional13 was employed in the
gradient-corrected DFT calculations. All the calculations
were performed by using the 6-31G* split-valence plus
polarization basis set.14 The optimized structures are
shown in Figure 2. The model compound of 3 (Figure 2a)
takes a partial cone (two benzene rings are oriented in
one direction and the remainder in another direction)
conformation with Cs symmetry. As shown in Figure 3a,
the optimized cone conformer (all the benzene rings are
oriented in the same direction) with C3v symmetry lies
10.2 kcal/mol above the partial cone conformer. Further-
more, a planar conformer with D3h symmetry lies 57.9
kcal/mol above the partial cone conformer. It is interest-
ing to note that the distance between the intraannular
protons pointing the same direction (1.78 Å) is within the
sum of van der Waals radii for the hydrogen atom (2.40
Å).15 This suggests that the most favorable conformation
of 3 is determined to minimize the intraannular proton-
proton repulsive interaction.16 On the other hand, the
model compound of 4 adopts a 1,3-alternate conformation
(adjacent benzene rings are oriented in the opposite
directions) with S4 symmetry (Figure 2b), and the
optimized geometry is in quite good agreement with a
reported X-ray structure10 of 4, except for the small
values of the calculated dihedral angles between adjacent
benzene rings. This is probably ascribed to removal of
N-methyl groups in the model calculations. As shown in
F igu r e 1. UV-vis spectra of 3-8 and DMPD in cyclohexane
at 298 K.
Ta ble 2. UV-Vis Sp ectr a l Da ta a of 3-8
compd
λmax (nm)
log ꢀ (M-1 cm-1
)
3
4
5
6
7
8
279, 252
288, 257
293, 249
290, 254
292, 252
293, 252
4.29, 4.34
4.49, 4.62
4.52, 4.59
4.02, 4.08
4.58, 4.60
4.46, 4.51
a
Recorded in cyclohexane at 298 K.
HX for cyclic trimer 3 shows the strongest low-field shift
of those of 3-8. The deshielding effect of 3 is probably
attributed to the influence of the diamagnetic ring
current of the two adjacent benzene rings due to the
highly intraannular strain. Macrocycles with ring sizes
other than three or four show a similar chemical shift.
On the other hand, the intraannular proton signal of 4
is shifted to a weak higher field as compared to those of
5-8. These results suggest that there is no intraannular
strain in the larger cyclic oligomers 5-8. In the 13C NMR
spectra of 3-8, no noticeable difference is found. As a
whole, the simple 1H and 13C NMR spectra of 3-8
indicate conformational mobility at room temperature in
solution.
UV-Vis Sp ectr oscop y. As shown in Figure 1, the
UV-vis spectra of the macrocycles 3-8 in cyclohexane
at 298 K have essentially the same features, showing two
bands at around 250 and 290 nm. For comparison, the
spectrum of DMPD is also added. The observed absorp-
tion wavelengths (λmax) and molar absorption coefficients
(ꢀ) are summarized in Table 2. In the present macrocyclic
oligomers, it is seen that the longest absorption wave-
length increases with increasing ring size of oligomers
up to the pentamer 5, and there is no more shift in going
from 6 to 8. This means that a certain limitation on
extensive conjugation occurs at around the pentamer 5.
(11) All the calculations were performed with the Gaussian 94 suite
of programs: Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M.
W.; J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T. A.;
Peterson, G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M.
A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, P. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94, Revision E.2; Gaussian, Inc.: Pittsburgh, PA, 1995.
(12) Becke, A. D. Phys. Rev. 1988, A38, 3098.
(13) Perdew, J . P. In Electronic Structure of Solids; Ziesche, P.,
Eschrig, H., Eds.; Akademie Verlag: Berlin, 1991.
(14) Hehre, W. J .; Radom, L.; Schleyer, P. v. R.; Pople, J . A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.
(15) Bondi, A. J . Phys. Chem. 1964, 68, 441.
Electr och em ica l P r op er ties. The first oxidation
potentials (E1ox) of 3-8 were determined by cyclic volta-
mmetry in CH2Cl2 with n-Bu4NClO4 as the electrolyte.
These are shown in Table 3. All the compounds exhibited
an irreversible oxidation which typically results from an

N-Methyl-Substituted Aza[1n]metacyclophane
J . Org. Chem., Vol. 64, No. 22, 1999 8239
F igu r e 2. BPW91/6-31G* optimized structures of the model
compounds (a) 3 and (b) 4. The plane defined by the nitrogen
atoms (shown in black) is parallel to the plane of the page.
Selected dihedral angles (deg): (a) C1-C2-N5-C6 22.5, C2-
N5-C6-C7 32.4, C7-C8-N12-C8′ 58.1; (b) C1-C6-N7-C2′
-10.8, C6-N7-C2′-C1′ -43.3.
Figure 3b, the optimized 1,2-alternate conformer with Cs
symmetry and cone conformer with C4v symmetry lie 7.3
and 31.0 kcal/mol above the 1,3-alternate conformer,
respectively.
F igu r e 3. Schematic diagrams of relative energies among
some conformers of (a) 3 and (b) 4.
Sch em e 2
Since 3 is expected to be the most strained one of cyclic
oligomers 3-8, we estimated the strain using the isodes-
mic reactions for the model compounds of 3 and 4, as
shown in Scheme 2.17 From this analysis, we obtained
the stabilization energies by macrocyclization of 1.7 and
8.0 kcal/mol per aniline unit for the model compounds 3
and 4, respectively. A decrease of this value in 3 clearly
shows an increase of the strain energy on going from 4
to 3. Hence, 3 can be considered as highly strained.
Here we calculated the 1H NMR chemical shifts within
the gauge-independent atomic orbital (GIAO) approach18
using the B3LYP/6-31G* optimized structures. As can be
seen in Table 4, the calculated chemical shifts for the
extraannular protons are in good agreement with the
experimental values. However, the shift for the intraan-
nular proton does not change on going from 3 to 4. This
is partly because the calculated dihedral angles between
adjacent benzene rings are slightly small compared with
those of the X-ray structure. Moreover, it seems probable
that 4 adopts the more distorted conformation in solution
than in the solid state to avoid the short proton-proton
contact. The calculated chemical shift of 9.2 for intraan-
(16) Unfortunately, only disordered crystals of 3 have been grown,
and to date, we have failed to refine the molecular structure completely
even by a low-temperature measurement. Benzene rings are orienta-
tionally disordered upward and downward to the plane defined by three
nitrogen atoms. Hence, the conformation of 3 is hardly determined.
Only two [1.1.1]metacyclophanes have been determined to adopt the
partial cone conformation by X-ray analysis: (a) Sergeev, V. A.;
Ovchinnikov, Yu. EÄ .; Nedel’kin, V. I.; Astankov, A. V.; Andrianova, O.
B.; Shklover, V. E.; Zamaev, I. A.; Struchkov, Yu. T. Bull. Acad. Sci.
USSR Div. Chem. Sci. 1998, 37, 1440. (b) Yoshida, M.; Goto, M.;
Nakanishi, F. Organometallics 1999, 18, 1465.
(17) A usefulness of the strain analysis using these isodesmic
reactions was suggested by one of the reviewers of this paper. For
isodesmic reactions, see ref 14.
(18) Wolinski, K.; Hilton, J . F.; Pulay, P. J . Am. Chem. Soc. 1990,
112, 8251-8260.

8240 J . Org. Chem., Vol. 64, No. 22, 1999
Ito et al.
Ta ble 4. Ca lcu la ted 1H NMR Ch em ica l Sh ifts (δ, p p m )bof
In tr a a n n u la r (HX) a n d Extr a a n n u la r (HA a n d HB)
Ar om a tic P r oton s of Mod el Com p ou n d s 3 a n d 4
δ
method
HX
HA
HB
3 (Cs)a
GIAO/HF/6-311G**
GIAO/HF/6-311+G**
7.31c
7.55c
7.40c
7.48c
6.57c
6.59c
a
3 (D3h
)
GIAO/HF/6-311G**
GIAO/HF/6-311+G**
9.19
9.27
7.59
7.59
6.59
6.58
4 (S4)a
GIAO/HF/6-311G**
GIAO/HF/6-311+G**
7.45
7.65
7.55
7.62
6.32c
6.39c
a
b
Optimized at the BPW91/6-31G* level. The magnetic shield-
ing of tetramethylsilane (TMS) as a standard was computed at
the same level of theory to calibrate the isotropic chemical shifts
(δ). c The protons corresponding to each chemical shift are clas-
sified into chemically different groups owing to the molecular
symmetry utilized in the calculation. However, the classified
protons should have the same time-averaged chemical environ-
ment and therefore the same chemical shifts in the actual NMR
spectrum. Hence, the calculated chemical shifts are averaged for
comparison with the experimental values.
nular proton in the planar conformer (D3h) of 3 suggests
that the closer the adjacent intraannular protons are, the
more downfield the signal for their protons shifts.
To better understand the irreversible redox properties
of 3-8, the monocationic state of the model compound 4
was computed at the BPW91/6-31G*//BPW91/6-31G*
level. The optimized structure retains the 1,3-alternate
conformation with S4 symmetry, similar to the most
favorable one in the neutral state. The calculated Mul-
liken spin density distributions indicate that the highest
spin density (+0.13) resides on the extraannular ortho
carbon atoms to the amino groups. This finding strongly
suggests that the benzidine formation reaction takes
place at the ortho position in the oxidation of the
macrocycles such as 3-8. In fact, it is known that
introduction of protecting substituent groups onto the 4-
and 6-positions of the m-phenylene moiety brings a
reversible redox behavior to N,N,N′,N′-tetraphenyl-m-
phenylenediamine in contrast with an irreversible be-
havior of the unsubstituted one.19 Therefore, it can be
rationalized that the macrocycles 3-8 show the irrevers-
ible oxidation potential.
F igu r e 4. Relative energy levels of the frontier Kohn-Sham
(KS) orbitals for the model compounds 3 and 4 on the basis of
BPW91/6-31G* calculations. The schematic KS orbitals are
depicted after the expansion of the nonplanar structure onto
the plane of the page.
Cyclic oligo(m-aniline)s such as 3-8 are classified as
coextensive non-Kekule´ molecules if they have a planar
structure. The coextensive non-Kekule´ molecules have
quasi-degenerate nonbonding molecular orbitals (NB-
MOs) which are mutually orthogonal but overlap in their
spatial distributions. Hence, when these MOs are singly
occupied by electron spins, strong exchange interaction
is expected and the energies of the high-spin states of
these molecules lie well below those of the corresponding
low-spin states. The mechanism of spin alignment is
essentially the same as that of Hund’s rule in atomic
systems.20 In 3-8, the molecular structures are highly
deviated from the planar structure, and therefore, the
MOs can be altered by their distortion. However, the
situation remains unchanged at least for the optimized
structures of model compounds 3 and 4, indicating that
they still have coextensive non-Kekule´ electronic struc-
tures, as shown in Figure 4. As a result, the tetracationic
state of 4 (tricationic state for 3) has the possibility of
being a high-spin molecule with a quintet (quartet for 3)
ground state.
Con clu sion
In the present study, we accomplished the preparation
of the aza-bridged [1n]metacyclophanes 3-8 with use of
a Pd(0)-catalyzed amination reaction under pseudo-high-
dilution conditions in moderate yields and found that
their spectral and electrochemical properties change with
increasing ring size (or decreasing intraannular strain)
up to around cyclic pentamer 5. In particular, it seems
that the cyclic trimer 3 has the most strained structure
in the reported [13]cyclophanes to the best of our know-
ledge. From the DFT calculations, the present macro-
cycles can be considered as a coextensive non-Kekule´
molecular system, which leads to realization of high-spin
(19) Yano, M.; Sato, K.; Shiomi, D.; Ichimura, A.; Abe, K.; Takui,
T.; Itoh, K. Tetrahedron Lett. 1996, 37, 9207.
(20) (a) Borden, W. T.; Davidson, E. R. J . Am. Chem. Soc. 1977, 99,
4587. (b) Borden, W. T. In Diradicals; Borden, W. T., Ed. Wiley: New
York, 1982.

N-Methyl-Substituted Aza[1n]metacyclophane
J . Org. Chem., Vol. 64, No. 22, 1999 8241
Da ta for Tr ia za [13]m eta cyclop h a n e (3): mp 130-131 °C;
1H NMR (CDCl3, 270 MHz) δ (ppm) 3.30 (s, 9H), 6.67 (dd, J )
8.1, 2.2 Hz, 6H), 7.10 (t, J ) 2.2 Hz, 3H), 7.12 (t, J ) 8.1 Hz,
3H); 13C NMR (CDCl3, 67.5 MHz) δ (ppm) 37.0, 112.0, 117.6,
129.1, 150.6; IR (KBr, cm-1) 685, 778, 868 (1,3-disubstituted
benzene); UV-vis (cyclohexane) λmax (log ꢀ) 252 (4.34), 279
(4.29); EI HRMS m/z (M+) calcd for C21H21N3 315.1735, found
315.1731.
molecules, despite having nonplanar molecular struc-
tures. Although 3-8 showed irreversible oxidation be-
haviors, it is anticipated that the introduction of suitable
substitutents onto the extraannular ortho positions to the
amino groups enables us to generate polycationic high-
spin states of these macrocycles.21 Preparation of deriva-
tives of this type is the subject of our future investigation.
Da ta for Tetr a a za [14]m eta cyclop h a n e (4): mp 280 °C
dec; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.20 (s, 12H), 6.42 (t,
J ) 2.4 Hz, 4H), 6.55 (dd, J ) 8.3, 2.4 Hz, 8H), 7.27 (t, J ) 8.3
Hz, 4H); 13C NMR (CDCl3, 100.5 MHz) δ (ppm) 40.2, 112.4,
113.8, 130.7, 149.4; IR (KBr, cm-1) 701, 775, 846 (1,3-
disubstituted benzene); UV-vis (cyclohexane) λmax (log ꢀ) 257
(4.62), 288 (4.49); FAB HRMS m/z (M+) calcd for C28H28N4
420.2314, found 420.2313.
Da ta for P en ta a za [15]m eta cyclop h a n e (5): mp 65-66
°C; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.19 (s, 15H), 6.58 (dd,
J ) 7.8, 2.0 Hz, 10H), 6.61 (t, J ) 2.0 Hz, 5H), 7.15 (t, J ) 7.8
Hz, 5H); 13C NMR (CDCl3, 100.5 MHz) δ (ppm) 40.0, 113.2,
113.4, 129.7, 149.7; IR (KBr, cm-1) 705, 783, 879 (1,3-
disubstituted benzene); UV-vis (cyclohexane) λmax (log ꢀ) 249
(4.59), 293 (4.52); EI HRMS m/z (M+) calcd for C35H35N5
525.2892, found 525.2885.
Da t a for Hexa a za [16]m et a cyclop h a n e (6): mp 280 °C
dec; 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.21 (s, 18H), 6.57
(dd, J ) 8.1, 2.2 Hz, 12H), 6.63 (t, J ) 2.2 Hz, 6H), 7.12 (t, J
) 8.1 Hz, 6H); 13C NMR (CDCl3, 100.5 MHz) δ (ppm) 40.2,
112.9, 113.0, 129.7, 149.5; IR (KBr, cm-1) 700, 762, 867 (1,3-
disubstituted benzene); UV-vis (cyclohexane) λmax (log ꢀ) 254
(4.08), 290 (4.02); EI HRMS m/z (M+) calcd for C42H42N6
630.3471, found 630.3495.
Da ta for Hep ta a za [17]m eta cyclop h a n e (7): mp 104-105
°C; 1H NMR (CDCl3, 270 MHz) δ (ppm) 3.17 (s, 21H), 6.55 (dd,
J ) 7.8, 2.4 Hz, 14H), 6.61 (t, J ) 2.4 Hz, 7H), 7.11 (t, J ) 7.8
Hz, 7H); 13C NMR (CDCl3, 67.5 MHz) δ (ppm) 40.2, 112.9,
113.4, 129.7, 149.7; IR (KBr, cm-1) 702, 776, 885 (1,3-
disubstituted benzene); UV-vis (cyclohexane) λmax (log ꢀ) 252
(4.60), 292 (4.58); EI HRMS m/z (M+) calcd for C49H49N7
735.4049, found 735.4075.
Exp er im en ta l Section
Gen er a l P r oced u r es. Commercial grade reagents were
used without further purification. Toluene and CH2Cl2 were
refluxed over and then distilled from calcium hydride under
argon before use. Elemental analyses were performed by the
Microanalytical Center, Kyoto University.
N-Meth yl-3-br om oa n ilin e (9) was prepared by the modi-
fied method of Willsta¨tter and Pfannenstiel22 from 3-bromoa-
niline via tosyl amide and methylation with dimethyl sulfate,
followed by hydrolysis of the resulting N-methyl tosyl amide
by the method of Snyder and Heckert.23 A mixture of 3-bro-
moaniline (25.0 g, 0.145 mol) and tosyl chloride (27.7 g, 0.145
mol) in pyridine (70 mL) was heated with stirring under reflux
for 20 min. After cooling, the reaction mixture was added to
120 mL of ice-cold water. The white precipitate was filtered
and washed thoroughly with water; the crude tosylated
product was quantitatively obtained and used without further
purification. Next, to a solution of the tosyl amide (15.5 g, 0.048
mol) and NaOH (3.3 g, 0.083 mol) in acetone-water (2:1) was
added dimethyl sulfate (9.9 g, 0.078 mol) dropwise with
stirring. After 2 h of stirring, the brown organic layer was
separated, washed with water, and dried over MgSO4. After
evaporation of the solvent, the crude N-methylated product
was obtained quantitatively as a pale yellow solid. Finally, a
mixture of N-methyl tosyl amide (14.2 g, 0.042 mol) and phenol
(14 g, mol) in 48% HBr (70 mL) was heated under reflux with
stirring for 1 h. After cooling, the reaction mixture was washed
with Et2O. To the aqueous layer was added NaOH aqueous
solution to alkaline. Liberated amine was taken up with Et2O.
The organic layer was dried over MgSO4. Evaporation of the
solvent afforded 9 (7.1 g, 91%) as a pale brown liquid: 1H NMR
(CDCl3, 270 MHz) δ (ppm) 2.77 (s, 3H), 3.78 (br s, 1H) 6.46-
6.50 (m, 1H), 6.70 (t, J ) 2.2 Hz, 1H), 6.77-6.81 (m, 1H), 7.00
(t, J ) 8.1 Hz, 1H). Anal. Calcd for C7H8NBr: C, 45.19; H,
4.33; N, 7.53; Br, 42.95. Found: C, 45.13; H, 4.26; N, 7.53; Br,
43.04.
Da ta for Octa a za [18]m eta cyclop h a n e (8): mp 221-222
°C; 1H NMR (CDCl3, 270 MHz) δ (ppm) 3.18 (s, 24H), 6.56 (dd,
J ) 7.8, 2.0 Hz, 16H), 6.63 (t, J ) 2.0 Hz, 8H), 7.09 (t, J ) 7.8
Hz, 8H); 13C NMR (CDCl3, 67.5 MHz) δ (ppm) 40.2, 112.8,
113.4, 129.6, 149.7; IR (KBr, cm-1) 702, 778, 884 (1,3-
disubstituted benzene); UV-vis (cyclohexane) λmax (log ꢀ) 252
(4.51), 293 (4.46); EI HRMS m/z (M+) calcd for C56H56N8
840.4628, found 840.4628.
Con d en sa tion Rea ction of N-Meth yl-3-br om oa n ilin e.
A mixture of 3-bromo-N-methylaniline (2.0 g, 11 mmol),
NaOBut (1.4 g, 15 mmol), and [PdCl2(P(o-tolyl)3)2] (0.17 g, 0.22
mmol) in toluene (90 mL) was heated under Ar atmosphere
at 100 °C for 19 h, following the reported procedure.24 After
the usual workup, the crude product was chromatographed
on SiO2 (n-hexane:CH2Cl2 ) 1:1 as eluent). A fraction (Rf )
0.65) afforded 4 as a white solid. Another fraction (Rf ) 0.45)
was purified by MPLC on SiO2 (n-hexane:ether ) 4:1 as
eluent). 3 (Rf ) 0.50), 5 (0.40), 6 (0.35), 7 (0.30), and 8 (0.20)
were isolated as white solids.
Ack n ow led gm en t. We are grateful to the reviewers
of this paper for useful comments. This work is a part
of the project of the Institute for Fundamental Chem-
istry (“Research for the Future” Program), supported
by the J apan Society for the Promotion of Science (J SPS
RFTF96P00206). Numerical calculations were partly
carried out at the Supercomputer Laboratory of the
Institute for Chemical Research of Kyoto University.
(21) A reviewer has remarked that replacement of the N-methyl
group by the other one without hydrogens improves the irreversible
redox behavior of the present system. This may be another way to
realize the high-spin azacyclophanes.
(22) Willsta¨tter, R.; Pfennenstiel, A. Chem. Ber. 1905, 38, 2244.
(23) Snyder, H. R.; Heckert, R. E. J . Am. Chem. Soc. 1952, 74, 2006.
(24) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1348.
Su p p or tin g In for m a tion Ava ila ble: Su p p or tin g In -
for m a tion Ava ila ble: Optimized BPW91/6-31G* geometries
of the model compounds 3 and 4, and the Mulliken spin
densities of the model compound 4+. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O990983M