Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement

Article abstract of DOI:10.1016/j.tetlet.2020.151673

Diaza(hetera)₂[1.1.1.1]paracyclophanes (PCPs) were prepared by the Chapman rearrangement. This is the first synthesis of highly strained and heteroatom-containing PCPs by a rearrangement reaction. The structures of the two precursors, [3.1.3.1]PCPs and [1.1.1.1]PCPs, are discussed in detail. In contrast to the small strain of [3.1.3.1]PCPs, [1.1.1.1]PCPs release their large strain by bending the aromatic rings and C_arom.-X angles. Interestingly, Arom.-X-Arom. angles are smaller than those of the corresponding strain-free model compounds.

Full text of DOI:10.1016/j.tetlet.2020.151673

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Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman
rearrangement
a
a
a
a
a
Hiroyuki Takemura a, , Akino Morikawa , Mari Tanaka , Akane Tatsumi , Yukiko Kubota , Natsuko Kaji ,
⇑
Ayako Hasegawa a, Fumiko Kumamoto a, Tomoko Obara a, Tetsuo Iwanaga b, Katsuya Sako c
a Department of Chemical and Biological Science, Faculty of Science, Japan Women’s University, Mejirodai 2-8-1, Bunkyou-ku, Tokyo 112-8681, Japan
b Department of Chemistry, Faculty of Science, Okayama University of Science, 1-1 Ridaicho, Okayama 700-0005, Japan
c Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Diaza(hetera)2[1.1.1.1]paracyclophanes (PCPs) were prepared by the Chapman rearrangement. This is the
first synthesis of highly strained and heteroatom-containing PCPs by a rearrangement reaction. The struc-
tures of the two precursors, [3.1.3.1]PCPs and [1.1.1.1]PCPs, are discussed in detail. In contrast to the
small strain of [3.1.3.1]PCPs, [1.1.1.1]PCPs release their large strain by bending the aromatic rings and
Carom.-X angles. Interestingly, Arom.-X-Arom. angles are smaller than those of the corresponding
strain-free model compounds.
Received 18 December 2019
Revised 22 January 2020
Accepted 23 January 2020
Available online xxxx
Keywords:
Ó 2020 Elsevier Ltd. All rights reserved.
[1n]Paracyclophanes
Chapman rearrangement
Cyclophanes
Macrocycles
Introduction
excess of p electrons. There is potential to apply such a structure
for the recognition of molecules and ions [6].
In this paper, we report the construction of the diaza[1.1.1.1]
PCP skeleton by Chapman rearrangement.
(Hetera)n[1n]PCP compounds have been used as raw materials
for polymers (by ring-opening reaction) and as host molecules in
host–guest chemistry [1]. It is expected that PCPs of n ꢀ 4 will have
large strains. However, it has been reported that tetrathia[1.1.1.1]
PCP and its sulfone derivative were obtained, albeit in low yields
(0.01–5%). The synthesis of CH2-bridged [1.1.1]PCP [2] and
[1.1.1.1]PCP [3] was achieved by finally forming a benzene ring.
In addition to C, S, and SO2 bridging moieties, a nitrogen-bridged
tetraaza[1.1.1.1]PCP has recently been isolated using Pd catalysis,
also in very low yield (0.3%) [4]. In contrast to other strained PCPs,
the decamethoxy-substituted [15]PCP (pillar[5]arene) has been
synthesized in a simple manner, and interesting studies on it and
its derivatives continue [5]. Since pillar[5]arene has a relatively
large cavity and no distortion, studies of host–guest chemistry
and applications for supramolecular chemistry have attracted
more attention than structural interest. The routes for synthesizing
such highly strained [1.1.1.1]PCP structures are limited, and the
synthesis of [1.1.1.1]PCPs with various bridging atoms are chal-
The Chapman rearrangement is a reaction in which an imi-
noether is rearranged to an acid amide when heated above
200 °C, and is one method for synthesizing diphenylamine deriva-
tives. The reaction mechanism is shown in I (Scheme 1). The phe-
nyl group to be rearranged is likely to possess an electron-
withdrawing group. Conventional Chapman rearrangements effi-
ciently convert iminoethers to amides in refluxing tetraglyme [7].
On the other hand, Tsubota et al. of Utsunomiya University
reported that the Chapman rearrangement occurs under milder
conditions (room temperature) in the presence of bases such as
Et3N and DBU when a hydroxyl group is introduced into the imi-
noether side chain [8]. Mechanism II in the Scheme 1 is the pro-
posed reaction mechanism of the improved rearrangement.
These reports suggest that the rearrangement would occur
under mild conditions in good yields when there is a nitro group
on the B ring. Tsubota et al. reported the synthesis of diazadioxo
[1.1.1.1]PCP 1c shown in Fig. 1 using this modified Chapman rear-
rangement [9]. However, they only presented a summary of these
results at annual meetings in Japan and did not publish them in
papers. Thus, the physical properties of the PCP 1c are unknown.
Therefore, we tested this method and succeeded in synthesizing
diaza(hetera)2[14]PCPs, 1a, 1b and the amide derivative of 1c
lenging. In this structure, four
p planes form a cavity with an
⇑
Corresponding author.
E-mail addresses: takemurah@fc.jwu.ac.jp (H. Takemura), iwanaga@chem.ous.ac.
jp (A. Morikawa), sako.katsuya@nitech.ac.jp (K. Sako).
https://doi.org/10.1016/j.tetlet.2020.151673
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
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H. Takemura et al. / Tetrahedron Letters xxx (xxxx) xxx
Scheme 1. Mechanisms of original (I) and improved (II) Chapman rearrangement.
available diamines 2 and phenylsalicylate in DMI (1,3-dimethyl-
2-imidazolidinone) at 200 °C for 4 h. Since these amides were only
soluble in highly polar solvents such as DMSO, purifications were
done by solvent washing (AcOEt), and characterizations were per-
formed by HRMS (FAB). These amides were then converted to
imino chlorides 4 in benzene or CPME (cyclomethylpentyl ether)
by refluxing with SOCl2 for 12–24 h. Imino chlorides are sensitive
to moisture in the air, react with water, and decompose immedi-
ately into amides and hydrochloric acid. Therefore, after the SOCl2
treatment, the solvents and the excess SOCl2 were distilled off and
the imino chlorides were immediately used for the cyclization. The
cyclization reaction was carried out under anhydrous and high
dilution conditions. After completion of the reaction, the solvent
was distilled off, and [3.1.3.1]PCP was obtained by column chro-
matography (CH2Cl2-AcOEt). Synthesis of [3.1.3.1]PCPs using imino
chloride enabled the synthesis of various cyclophanes as shown in
Fig. 2. Significant differences in yields seem to be related to the ring
size of 6. The possibility of the rearrangement of these compounds
6f-k will be studied in the near future. Of these, 6b and 6e were
recrystallized from an appropriate solvent to obtain crystals suit-
able for crystallography.
Fig. 1. Structures of diaza[1.1.1.1]PCPs.
(7c). We also report syntheses of the [3.1.3.1]PCP precursors. As a
comment, recent report described the synthesis of meta-bridged
structure of 1a by Pd-catalized reaction. Although the meta cyclo-
phane has no structural strain, it showed very interesting deep
blue thermally activated delayed fluorescence (TADF) and room
temperature phosphorescence (RTP) dual emission [10].
Results and discussion
Synthesis of [3.1.3.1]PCPs
Structures of [3.1.3.1]PCPs
The synthetic route of diaza[1.1.1.1]PCPs is shown in Scheme 2.
The structures of 6b and 6e are shown in Fig. 3. These [3.1.3.1]
Amides 3 were obtained in high yields by heating commercially
PCPs are slightly distorted. In reference 1, optimization of
Scheme 2. Synthetic route to [3.1.3.1]PCPs as precursors of [1.1.1.1]PCPs.
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
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H. Takemura et al. / Tetrahedron Letters xxx (xxxx) xxx
3
Fig. 2. Structures and yields of synthesized [3.1.3.1]PCPs, 6f-6k.
diphenylmethane, diphenylsulfone, diphenylether, and dipheny-
Rearrangements of cyclophanes
lamine structures was performed by HF calculations to calculate
angles and bond lengths [11]. These were used to estimate the
cyclophane distortions. In fact, the benzene rings of 6b are slightly
warped inward (Àh1 = 0.35–2.04°: See Fig. 5 for definition of h1) as
opposed to the cyclophanes after rearrangement (described
below), and the Ar-CH2-Ar angle (113.6°) and the CAC bond
lengths between the methylene and benzene rings (CAC: 150.8
and 151.9 pm) are the same as those of diphenylmethane (113.5°
and 152 pm). The Carom.-SO2-Carom. angle of 107.5° is almost the
same as the theoretical value of 105.3° in diphenylsulfone. The
Reactions
Considering the reaction mechanism, it is necessary that the Y
unit of cyclophane 6 in Scheme 2 be an electron-withdrawing
group so that rearrangement easily occurs. To confirm this, we
compared the ease of rearrangement of 6a (X = SO2, Y = SO2), 6b
(X = CH2, Y = SO2), 6c (X = C@O, Y = C@O), 6d (X = SO2, Y = CH2)
and 6e (X = CH2, Y = CH2) with electron-withdrawing and -donat-
ing groups for Y (Scheme 3). The rearrangement was carried out by
reacting the cyclophanes and DBU in DMF at 30 °C. As expected,
the rearrangements of 6a, b, and c were completed in 5 min, and
[1.1.1.1]PCPs 7a, b, and c were formed in moderate yields. How-
ever, under the rearrangement condition, 6d (X = SO2, Y = CH2)
was recovered and rearranged product was not identified. In the
case of 6e (X = CH2, Y = CH2), severe conditions, e.g., 50 °C in
DMF with DBU for 24 h or boiling in tetraglyme for 1 h [7], were
Carom.-S bond lengths, 176.3 and 176.7 pm, are consistent with
the theoretical value (177.5 ppm) within the range of error [1].
The aromatic rings of 6e are also slightly warped inward
(Àh1 = 0.11–2.19°), but the Ar-CH2-Ar angles (113.5 and 115.1°)
and the CAC bond lengths between the methylenes and benzene
rings (150.9–152.2 pm) are the same as those of diphenylmethane
(113.5°, CAC: 152.0 pm).
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
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H. Takemura et al. / Tetrahedron Letters xxx (xxxx) xxx
Fig. 3. X-ray structures of [3.1.3.1]PCPs 6b (a) and 6e (b).
employed. However, only a trace amount of rearranged cyclophane
was identified by NMR spectroscopy, but it could not be isolated.
The rearrangement products [1.1.1.1]PCPs 7 having amide side
chains were poor in crystallinity and could not be crystallographi-
cally analyzed.
h1 = 3.1–5.6°. In addition, the value of h2 (Arom.-SO2-) is curved
from 5.3 to 7.6°. h2 (Arom.-NH-) is slightly bent at 0.4–1.4°. These
deformations eliminate the distortion of the whole molecule.
Conversely, Carom.-SO2-Carom. = 100.9° is narrower by 4.4° than
the theoretical value (105.3°) of diphenylsulfone. Similarly,
Hydrolysis of [1.1.1.1]PCPs 7 was achieved by refluxing with
conc. aq. KOH in methanol for 24 h. By this treatment, 1a was
obtained in 79.4% yield and 1b in 84.7% yield (Scheme 3). However,
7c was difficult to hydrolyze. Several changes in conditions were
attempted, but only traces of 1c with large amounts of impurities
were identified by 1H NMR spectral analysis, the remainder being a
mixture of unidentifiable compounds. We suspect cleavage of the
cyclic structure occurred, but the exact reason for this difficulty
of hydrolysis is still unknown.
C
arom.–NH-Carom. = 115.3° is narrower than the theoretical value
of 129.9° in diphenylamine by 14.6°. The bond length,
C
C
arom.-S = 176 pm (theoretical: 177.5 ppm), is normal, and
arom.-N = 142–143 pm is slightly extended (theoretical: 140.0 pm).
In 1b, the angle Carom.–CH2-Carom. = 106.7° is narrower than the
theoretical value of diphenylmethane, 113.5°, and Carom.-SO2-
arom. = 99.4° is narrower than the theoretical value of diphenylsul-
C
fone (105.3°) by 5.9°. The angles Carom.–NH-Carom. = 112.6 and
114.8° are narrower by 17.3–15.1° compared with 129.9° of
diphenylamine. The deviation of these angles from theoretical val-
ues can be interpreted as follows. In the case of model compounds
(diphenylmethane), \Ar-CH2-Ar becomes 113.5° by the sp2 charac-
ter of the CAH by conjugation with the benzene ring. However, it is
considered that the –CH2– of 1b adopts sp3 hybridization due to
the lack of conjugation with the aromatic ring of 1b. The same
Structures of [1.1.1.1]PCPs 1a and 1b
The structures of 1a and 1b are shown in Fig. 4. This is the third
case in which the structures of [1.1.1.1]PCPs have been revealed.1, 4
Cyclophane 1a forms a face-to-face structure, but 1b does not. A
schematic diagram of the molecular deformation is shown in
Fig. 5. Deviation of 1a from the plane of the benzene ring is
can be considered for 1a. The bond length of 1b, Carom.–CH2
152 pm, is consistent with the theoretical value (152.0 pm). The
=
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2020.151673

H. Takemura et al. / Tetrahedron Letters xxx (xxxx) xxx
5
Scheme 3. Rearrangements of [3.1.3.1]PCPs to [1.1.1.1]PCPs.
Carom.-N = 142–145 pm, similar to 1a, extends slightly beyond the
calculated value of diphenylamine (140 pm). The values of Carom.
-
S = 176 and 177 pm remain the same as the 177.5 pm of diphenyl-
sulfone. The deviation of 1b from the plane of the benzene ring (h1)
is 3.9–6.4°, similar to 1a, h2 (Arom.-SO2-) is 5.5–7.6°, h2 (Arom.–
CH2–) is 3.9–5.2°, and h2 (Arom.–NH–) is 0.4–3.7°. From the above,
in the [1.1.1.1]PCP structures, the aromatic rings swell outward,
and the distortion is alleviated by the deformation of the aromatic
rings. Also, by the formation of the [1.1.1.1] structure, \Ar-X-Ar
becomes narrower than the HF calculation values because X has
more sp3 character as compared to the model compounds. These
[1.1.1.1]PCPs are stable, have high melting points, and do not
decompose to any extent at 200 °C. From this, it is presumed that
the distortion is largely alleviated by the above-mentioned defor-
mation. Table 1 summarized those distortion angles of 1a and 1b.
Fig. 4. X-ray structures of 1a (a) and 1b (b).
Table 1
Distortion angles of the compounds 1a and 1b.
1a (°) (theoretical values)1
1b (°)
h1
3.1–5.6
h1
3.9–6.4
\Carom.-SO2-Carom
\Carom.–NH-Carom
\Carom.–CH2-Carom
\Carom.-SO2-Carom.
\Carom.–NH-Carom.
h2
.
.
100.9 (105.3)
115.3 (129.9)
106.7 (113.5)
99.4 (105.3)
112.6, 114.8 (129.9)
\Arom.-SO2-
\Arom.–NH-
\Arom.-SO2-
\Arom.–CH2-
\Arom.–NH-
5.3–7.6
0.4–1.4
5.5–7.6
3.9–5.2
0.4–3.7
Fig. 5. Bending of benzene rings of cyclophanes.
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
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6
H. Takemura et al. / Tetrahedron Letters xxx (xxxx) xxx
Fig. 6. Molecular packing of compound 1a. (a) Top view, (b) side view.
Molecular packing in the crystals of the cyclophanes
Appendix A. Supplementary data
Cyclophanes 1a, 1b, 6b, and 6e have molecules arranged in col-
umns in their crystals, and intramolecular cavities form channels.
As an example, the packing diagram of 1a is shown in Fig. 6. Those
of 1b, 6b and 6e are shown in the Supporting Information. The cav-
ity diameters are 647 Â 647 in 1a, 633 Â 625 in 1b, 666 Â 662 in
6b, and 655 Â 669 pm in 6e (see Supporting Information). Investi-
gations of this architecture for applications such as gas-adsorption
or inclusion of ions are future subjects [5,12].
Experimental data of the compounds. Crystallographic data for
compounds 1a, 1b, 6a, and 6e (CIF) and graphics. 1H and 13C NMR
spectra of synthesized compounds (PDF). Supplementary data to
this article can be found online at https://doi.org/10.1016/j.tetlet.
2020.151673.
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By applying the Chapman rearrangement, highly strained diaza
[1.1.1.1]PCPs containing heteroatoms were successfully synthe-
sized in moderate yields. Previously, the construction of the
[1.1.1.1]PCP skeleton was performed by the formation of a benzene
ring in the final step or SNAr reaction [1] or by catalytic cyclization
[4]. However, these PCPs were obtained in very poor yields. Our
present work provides the first successful example of a rearrange-
ment synthesis, and the simplicity of the synthetic route is attrac-
tive. The drawback is that rearrangement reactions are unlikely to
occur if there are no electron-withdrawing groups on the oxygen-
bridging side of the [3.1.3.1]PCP precursors. However, the possibil-
ity of introducing various bridging units (atoms) or functionaliza-
tion of the aromatic rings will expand the applicability of PCPs.
[1.1.1.1]PCP has a relatively small and rigid cavity surrounded by
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p
electrons. Therefore, although organic molecules cannot be
included, there is a possibility that metal ions [5] or small gas
molecules can be complexed in the cavity. The [1.1.1.1] skeleton
is rigid and thus, high selectivity of these guests is expected.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Please cite this article as: H. Takemura, A. Morikawa, M. Tanaka et al., Syntheses of diaza(hetera)2[1.1.1.1]paracyclophanes by Chapman rearrangement,
Tetrahedron Letters, https://doi.org/10.1016/j.tetlet.2020.151673