[2.2]Paracyclophane-Bis(triazole) Systems: Synthesis and Photochemical Behavior

Article abstract of DOI:10.1002/chem.201701593

Mono-, pseudo-gem, and pseudo-para ethynylcyclophanes and bis(azides) have been employed as addition partners in CuAAC reactions to design and build complex extended molecular scaffolds. The reactivity of the resulting triazoles was investigated under photochemical conditions. A variety of newly substituted [2.2]paracyclophanes were identified; deazotization of pseudo-gem and pseudo-para adducts provided indolophane derivatives. An intramolecular stabilization effect was observed in the case of pseudo-gem derivatives. A photochemical rearrangement from a pseudo-para adduct to a pseudo-ortho product was identified.

Full text of DOI:10.1002/chem.201701593

A Journal of
Accepted Article
Title: [2.2]Paracyclophane-Bis(triazole) Systems: Synthesis and
Photochemical Behavior
Authors: Henning Hopf, Lucian Bahrin, Laura Sarbu, Peter Jones, and
Lucian Birsa
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To be cited as: Chem. Eur. J. 10.1002/chem.201701593
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[2.2]Paracyclophane-Bis(triazole) Systems: Synthesis and
Photochemical Behavior
Dedicated to Professor Roald Hoffmann on the occasion of his 80th birthday
Lucian G. Bahrin,[a] Laura G. Sarbu,[a,b] Peter G. Jones,[c] Lucian M. Birsa*[a,b] and Henning Hopf*[a]
Abstract: Mono, pseudo-gem and pseudo-para ethynylcyclophanes
and bis(azides) have been employed as addition partners in CuAAC
reactions to design and build complex extended molecular scaffolds.
The reactivity of the resulting triazoles was investigated under
4,7,13,16-tetraethynyl[2.2]paracyclophane 7, which have all
been prepared from the corresponding brominated and/or
formylated derivatives.[5] Since then, these compounds have
been used in coupling reactions,[6] addition reactions,[7] synthesis
of polymers [8] and of luminescent compounds.[9]
photochemical conditions.
A
variety of newly substituted
[2.2]paracyclophanes were identified; deazotization of pseudo-gem
and pseudo-para adducts provided indolophane derivatives. An
intramolecular stabilization effect was observed in the case of
pseudo-gem derivatives. A photochemical rearrangement from a
pseudo-para adduct to a pseudo-ortho product was identified.
Azido-subtituted paracyclophanes have been far less
studied than their ethynyl counterparts. Figure 2 displays three
examples, two of them previously reported in the literature,
namely 4-azido[2.2]paracyclophane, 8,[10] used in the synthesis
of
some
imidazole-[10]
and
triazole-[11]
bearing
[2.2]paracyclophanes, and pseudo-gem bis(azido)[2.2]para-
cyclophane, 9.[12]
Introduction
Since its discovery in 1949 by Brown and Farthing,[1] [2.2]para-
cyclophane has been intensely studied by chemists. Consisting
of two benzene rings bound together by two ethano bridges, the
[2.2]paracyclophane core can undergo chemical transformations
specific to both aliphatic and aromatic compounds, resulting in a
wide variety of functionalized [2.2]paracyclophanes. Both the
parent hydrocarbon and its derivatives have been used in
1
2
asymmetric
synthesis.[4]
catalysis,[2]
optoelectronics[3]
and
polymer
Acetylene-substituted paracyclophanes are important be-
cause of the ability of the acetylene moiety to easily undergo
coupling and addition reactions, leading to new derivatives that
contain one or more units of the [2.2]paracyclophane core.
Figure 1 presents seven acetylene-subtituted paracyclophanes,
3
4
5
namely
4-ethynyl[2.2]paracyclophane
1,
pseudo-gem
pseudo-ortho
pseudo-meta
pseudo-para
bis(ethynyl)[2.2]paracyclophane
bis(ethynyl)[2.2]paracyclophane
bis(ethynyl)[2.2]paracyclophane
bis(ethynyl)[2.2]paracyclophane
2,
3,
4,
6
7
Figure 1. Ethynyl[2.2]paracyclophane derivatives.
5,
4,5-bis(ethynyl)-
[2.2]paracyclophane 6 and the cross-tetrasubstituted derivative
N3
N3
N3
N3
[a]
Prof. Dr. H. Hopf, Prof. Dr. L. M. Birsa, Dr. L. G. Bahrin, Dr. L. G.
Sarbu,
Institute of Organic Chemistry, Technical University of
Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany
E-mail: h.hopf@tu-braunschweig.de
N3
8
9
10
[b]
[c]
Prof. Dr. L. M. Birsa, Dr. L. G. Sarbu,
Department of Chemistry, Al.I. Cuza University of Iasi, 11 Carol I,
700506-Iasi, Romania
E-mail: lbirsa@uaic.ro
Prof. Dr. P. G. Jones,
Figure 2. Azido-substituted paracyclophanes.
In a previous paper,[13] we studied the synthesis and
properties of some [2.2]paracyclophane derivatives in which two
triazole rings were bound to a [2.2]paracyclophane core by
methylene units. In an attempt to extend the study to triazole-
bearing [2.2]paracyclophanes, this paper presents the synthesis
Institute of Inorganic and Analytical Chemistry, Technical University
of Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany
Supporting information for this article is given via a link at the end of
the document.
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of some new triazole[2.2]paracyclophane hybrids, and describes
their behavior when exposed to UV radiation.
bridges with lengthened C–C bonds and widened angles, and
rings with a flattened boat conformation and narrow angles at
the bridgehead carbons. The same is valid for the other
cyclophane structures presented here. For compound 13, the
two independent molecules differ in the orientation of the phenyl
rings (torsion angles C5–N1–C22–C23 –33.2, +21.1°); a least-
squares fit of the other non-H atoms gave an r.m.s. deviation of
0.08 Å. N.B. Packing diagrams are presented and discussed in
the Supplementary Material.
Results and Discussion
Mono(triazolyl)[2.2]paracyclophanes
The first addition experiment was performed using 4-
ethynyl[2.2]paracyclophane 1 and 4-azido[2.2]paracyclophane 8,
with 5 mol % CuSO4/ascorbic acid as a catalyst. The two
derivatives were dissolved in dichloromethane, while the catalyst
was dissolved in an ethanol/water mixture. The two resulting
solutions were then combined and vigorously stirred. After
several hours, however, TLC monitoring displayed no change.
We thus replaced the catalyst by Cu(PPh3)3Br, a compound that
is soluble in dichloromethane. Again, acetylene 1 and azide 8
were dissolved in dichloromethane, along with 5 mol % of the
catalyst system, and the reaction was monitored by TLC
analysis. After several hours at room temperature, however,
again no change was observed and the situation remained
unchanged even when the temperature was raised to 40 °C. For
our third attempt, we decided to employ a different Cu(I) catalyst,
[Cu(phen)(PPh3)2]NO3 I (Figure 3), previously reported to yield
good results,[14] as well as raise the temperature of the reaction
mixture. The catalyst was synthesized according to a literature
procedure.[15]
N
N
N
Ph
catalyst I, toluene, 60 o
C
12
91%
N3
N
N
N
8
catalyst I
toluene
11
62%
80 o
C
N
N
N
1
Ph N3
catalyst I, toluene, 60 o
13
68%
C
Scheme 1. Synthesis of mono(triazole)[2.2]paracyclophanes.
NO3
N
N
Cu
Ph3P
PPh3
I
Figure 3. CuAAC reaction catalyst I
Acetylene 1, azide 8, and 2 mol % catalyst I were then
stirred in toluene at 80 °C. After 24 h, no more starting material
was detected by TLC. The solvent was removed in vacuo and
the resulting residue was separated by flash chromatography on
silica gel, yielding triazole 11 (Scheme 1). By replacing
acetylene 1 by phenylacetylene, or azide 8 by phenylazide, and
lowering the reaction temperature to 60 °C, previously described
derivative 1211b and triazole 13 were synthesized (Scheme 1).
The most prominent signal in the 1H NMR spectra of compounds
11-13 belongs to the triazole proton, which appears as a sharp
singlet, around 8.00 ppm. Most of the other aromatic proton
signals overlap, resulting in multiplets. The aliphatic protons
belonging to the ethano bridges can be found between 2.60 and
4.10 ppm. Further proof of the newly formed triazole ring is a
signal at about 148.0 ppm in the 13C NMR spectra of compounds
11-13, which belongs to the C4 carbon atom of the heterocyclic
ring.
The stereochemical outcome of this cycloaddition is
complicated (see below), so we decided to get an unambiguous
structure assignment first. This was achieved by X-ray structural
analysis. Upon slow diffusion of pentane into a chloroform
solution of 12 or 13, single crystals suitable for X-ray diffraction
were obtained (Figure 4).[16] The molecules of 12 and 13 show
the usual symptoms of strain in [2.2]paracyclophanes, namely
Figure 4. Molecular structure of compounds 12 (above) and 13
(below, two independent molecules). Ellipsoids represent 50%
probability levels.[16]
As can be seen from Figure 4 only one regioisomer is generated
in both cases. From closer inspection of the structures it can be
inferred that the route leading to these isomers avoids steric
interactions between the aromatic parts of both substrate
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N
N
molecules: one obtains the shown "stretched" regioisomers,
rather than the (not shown) "congested" forms.
N3
N3
N
cat. I
dioxane, 90 oC 6 h
2
R
N
N
Because of the chiral plane of 1 and 6 the adducts 12 and
13 are produced as racemates. The case of the hybrid material
11, of which we unfortunately could not get single crystals
suitable for X-ray diffraction measurements is stereochemically
more complex. Assuming again that one regioisomer is formed
preferentially (the one shown in Scheme 1) we now have two
chiral planes and thus could form a mixture of two pairs of
diastereomers (one is RS and SR, the other is RR and SS).
N
R
R
9
14
15
15a: R=H, 88%
15b: R=Br, 58%
Scheme 2. Reaction of bis(pseudo-gem triazole)
acetylenes.
9 with
1
Indeed, the careful analyses of the H NMR spectrum confirms
N
N
N
this: two different sets of signals were identified in a 1:11 ratio.
Because of the size of the paracyclophanyl groups, the major
product probably corresponds to an interaction of 8 with 1,
where both bulky substituents are in a mutual anti orientation.
This approach avoids steric interference to the greatest extent.
N
cat. I
2 N3
R
dioxane, 90 oC 10 h
N
N
R
R
2
16
17
17a: R=H, 56%
17b: R=Br, 50%
17c: R=I, 51%
Bis(pseudo-gem triazolyl)[2.2]paracyclophanes
Scheme 3. Reaction of bis(pseudo-gem acetylene) 2 with
azides.
In an attempt to decrease the reaction times, we decided to
identify a more suitable solvent for the synthesis of triazole-
bearing [2.2]paracyclophane units. Trials were conducted in
acetonitrile, cyclohexane and ethanol at 70 °C and in dioxane,
DMSO and toluene at 90 °C. Each trial was performed with 0.1
mmol of both acetylene 1 and azide 8, with 2.4 mol% cat. I, in 2
mL of solvent. TLC monitoring revealed that the shortest
reaction time of 3 h was achieved for dioxane. After 5 h, the
reaction in toluene was complete, whereas the remaining four
runs showed only traces of triazole 11, at which point the
reactions were terminated.
Having identified a suitable catalyst and solvent, we next
investigated the synthesis of triazoles in which two heterocyclic
rings are bound to a [2.2]paracyclophane core in the pseudo-
gem positions. This was achieved by reacting azide 9 or
acetylene 2 with the appropriate acetylenes or azides, as
presented below (Scheme 2 and 3). As above, the difference
between products 15 and 17 consists in the way the
paracyclophane unit is bound to the triazole rings; thus, in
compounds 15a,b the [2.2]paracyclophane moiety is connected
to the N1 atoms of the triazole rings, but in compounds 17a-c to
the C4 atoms of the triazole rings. These copper-catalyzed
cycloaddition reactions provided the corresponding pseudo-
geminal bis(1,2,3-triazoles) in a regioselective manner in yields
between 50 and 88%. Possibly the bis(azide) prefers an
orientation in solution in which the two functional groups are
oriented in a parallel fashion. In the cycloaddition step, the
incoming dipolarophile clearly prefers an orientation which tends
to minimize steric interaction with the cyclophane scaffold,
similarly as observed above. In the two-step click process, the
monoadduct, formed as a probable intermediate, clearly does
not undergo an intramolecular cycloaddition of the remaining
azide function to the newly formed triazole ring. This simplifies
the process and makes multiple 1,3-dipolar cycloadditions of
appropriately substituted [2.2]paracyclophanes preparatively and
stereochemically more attractive.
Despite these structural differences, the spectra of these
two types of triazoles present similar characteristics. The signals
belonging to the triazole protons appear in the H NMR spectra
1
of compounds 15a,b and 17a (in CDCl3) as singlets around 7.90
ppm. For triazoles 17b,c (in DMSO-d6), the same signals can be
found around 8.60 ppm. The 13C NMR spectra of all five
triazoles display the signals belonging to the heterocyclic C4
carbon atom at about 147.0-148.0 ppm. Single crystals suitable
for X-ray diffraction were obtained for compounds 15a,b (Figure
5)[17] and 17b (Figure 6)[18] through the diffusion of pentane into a
chloroform solution (15a,b) or recrystallization from DMF (17b).
Compound 15b crystallizes as a deuteriochloroform solvate.
Figure 5. Molecular structure of compounds 15a (above) and
15b (below, deuteriochloroform solvate). Ellipsoids represent
50% probability levels.[17]
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Figure 6. Molecular structure of compound 17b. Ellipsoids
represent 50% probability levels.[18]
Because in the solid state of compound 15a the distance
between the two triazole rings is less than 3.8 Å, we decided to
investigate how the two heterocyclic rings interact with each
other under both thermal and photochemical conditions. On
refluxing a solution of triazole 15a in toluene (b. p. 110 °C) for
several hours, no change could be observed. When p-xylene (b.
p. 138 °C) was used, the starting material decomposed
completely and no defined products could be isolated. Next, we
examined intramolecular interactions under photochemical
conditions. A 1.1x10-3 M solution of 15a in toluene, under a
constant flow of nitrogen gas, was irradiated for 2 h using a
TQ150 high pressure mercury lamp. The solvent was then
removed under vacuum and the remaining residue was
separated using flash chromatography on silica gel, yielding
unreacted starting material and two new products (Scheme 4).
Figure 7. Molecular structure of compounds 18 (above) and 19
(below). Ellipsoids represent 30% probability levels for 18 and
50% for 19.[19]
N
N
N
N
H
N
N
N
N
N
N
N

h
H
+
N
N
N
Photolysis or pyrolysis of the 1,4-diaryl-1,2,3-triazole ring
can lead to the formation of carbene intermediates. These may
in turn lead to indoles, or undergo Wolff rearrangements, to give
ketenimines.[20] Scheme 5 presents a tentative sequence of
these transformations for compound 15a.
When subjected to UV radiation, triazole 15a eliminates a
molecule of nitrogen, with the formation of carbene 20. This can
then either form indole 18 by C-H-insertion into the neighboring
benzene ring, or ketenimine 21 via a Wolff rearrangement.
Subsequently, 21 could add one molecule of water during
workup, leading to the formation of amide 19.
15a
18
42%
19
20%
O
Scheme 4. Photolysis of bis(pseudo-gem triazole) 15a.
The isolated yields were 42% for indole 18 and 20% for
amide 19, the remaining 38% consisting of a mixture of
unreacted material along with traces of amide 19. The H NMR
1
spectrum of indole 18 displays the signal of the H1 hydrogen
atom of the indole ring as a singlet at 8.28 ppm, while the
triazole proton appears as a singlet at 7.74 ppm. The 13C NMR
spectrum of the same compound shows the signal of the C4
carbon atom of the triazole ring at 146.9 ppm. The 1H NMR
spectrum of amide 19 displays the signal of the triazole proton at
7.94 ppm, while the amide proton displays a signal at 7.90 ppm.
The two hydrogen atoms  to the carbonyl group are registered
as an AB-quartet system at 3.42 and 3.30 (2J=14.3 Hz). The 13
C
NMR spectrum shows a signal at 168.3 ppm, belonging to the
carbonyl carbon atom, while the C4 carbon atom of the triazole
ring appears at 148.1 ppm. Single crystals suitable for X-ray
diffraction were obtained for 18 and 19 by slow diffusion of
pentane into
a chloroform solution of the corresponding
derivative (Figure 7).[19] The annelated indole ring of 18 does not
significantly alter the flattened boat form of the cyclophane ring
to which it is attached (the same is true for the other fused-ring
derivatives presented below). The molecule of 19 contains an
intramolecular N–HN hydrogen bond from the amide group to a
triazole nitrogen.
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N
N
N
N
1) BuLi
2) TsN3
Br
N3
N3
N3
N
N
N
+
+

-N2
h
THF
N
N
Br
N3
Br
N
22
10
20%
23
8
20
H
15a
Scheme 6. Synthesis of pseudo-para bis(azido)[2.2]paracyclo-
phane 10.
N
C
N
N
N
N
N
Upon separation of the reaction mixture, bisazide 10 was
obtained in 20% isolated yield and 6% was unreacted starting
material, the remaining 74% being a mixture of bis(azide) 10,
monoazide 8 and bromoazide 23 (as identified by 1H NMR
analysis), the latter probably being the result of an incomplete
bromometal exchange of 22. The next step consisted of reacting
bis(azide) 10 with phenylacetylene, as depicted in Scheme 7.
This led to the formation of triazole 24a as a colorless solid,
poorly soluble in all common solvents. Because we wished to
record an X-ray structure, we decided to synthesize another
pseudo-para bis(triazole), using 1-hexyne instead of
phenylacetylene as a trapping reagent, in order to increase the
solubility of the product. Indeed, triazole 24b exhibited a much
higher solubility in solvents such as dichloromethane or
H
N
N
18
21
H2O
N
N
N
H
N
19
O
Scheme 5. Plausible mechanism for the formation of the
photolysis products 18 (dashed arrows) and 19 (full arrows).
1
chloroform. The H NMR spectra of triazoles 24a, b confirm the
formation of the triazole rings. The triazole protons are found at
9.15 ppm for 24a and 7.27 ppm for 24b. In the 13C NMR spectra,
the C4 carbon atoms of the newly formed heterocyclic rings
absorb at 146.9 ppm for 24a and 148.3 ppm for 24b.
In an attempt to photolyse both triazole rings, we raised
the irradiation time from 2 to 7 h. However, only indole 18 (31%)
and amide 19 (28%) were recovered. By changing the solvent to
acetonitrile and irradiating the solution for 2.5 h, we isolated
indole 18 (19%), amide 19 (7%) and unreacted starting material
(35%). In a further attempt, we added benzophenone as a
sensitizer to a toluene solution of 15a and irradiated the reaction
mixture for 2 h. However, again only indole 18, amide 19 and
unreacted starting material were recovered. The fractions
containing the two reaction products also displayed considerable
amounts of decomposed material and no further purification was
N
N
N3
N
R
R
R
cat. I, dioxane
60-90 oC, 10-16 h
N3
N
N
N
10
24
24a: R=Ph, 63%
24b
: R=nC4H9, 61%
attempted. Using diacetyl as
a
sensitizer led to the
decomposition of triazole 15a, with possible traces of indole 18
and amide 19 being identified by TLC. Irradiation of a pure
sample of indole 18 in toluene for 4 h was also performed,
however no new products were identified by TLC and therefore,
no workup was performed for this attempt.
Scheme 7. Synthesis of pseudo-para bis(triazoles) 24.
Single crystals suitable for X-ray diffraction were obtained
for both bis(azide) 10 and triazole 24b, by slow diffusion of
pentane into a chloroform solution. For the poorly soluble
triazole 24a, an NMR tube containing a dilute chloroform
solution was set aside until all the solvent had evaporated,
leaving single crystals (Fig. S7) suitable for X-ray diffraction. The
three structures are presented in Figures 8 and 9.[21,22] The
molecule of 10 displays non-crystallographic inversion symmetry,
with an r.m.s. deviation of 0.03 Å.
Pseudo-para bis(triazole)[2.2]paracyclophanes
Because the second triazole ring did not react in any of the
conditions reported above, we assumed it might be stabilized by
the indole/amide function in the pseudo-geminal position. To test
this hypothesis, we decided to synthesize
a
new
[2.2]paracyclophane bis(triazole), where the two heterocyclic
rings occupied the pseudo-para positions, thus limiting the
possible interactions between them. Toward this end, we first
prepared pseudo-para bis(azido)[2.2]paracyclophane 10 by
reacting pseudo-para bis(bromo)[2.2]paracyclophane with n-
butyllithium, followed by tosyl azide treatment, according to a
previously described procedure (Scheme 6).[10]
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N
N
N
N
N
N
24a

h
4 h
N
N
O
N
N
H
N
N
N
N
H
25
26
7%
16%
+
Figure 8. Molecular structure of compound 10. Ellipsoids
represent 50% probability levels.[21]
N
O
H
N
H
N
N
N
N
H
27
28
12%
11%
N
silica gel
H
NH2
29
Scheme 8. Photolysis of bis(pseudo-para triazole) 24a.
The reaction mixture was submitted to flash chromato-
graphy, allowing isolation of the different products. The detailed
NMR analysis of compound 25 indicated that it was an indole
derivative. The H1 hydrogen atom of the indole ring absorbs as
1
Figure 9. Molecular structure of compounds 24a (above) and
24b (below). Ellipsoids represent 50% probability levels.[22]
a singlet at 8.36 ppm in the H NMR spectrum of 25, while the
triazole proton can be found as a singlet at 8.09 ppm (2D NMR
analysis). ESI-MS analysis indicated the mass of 25 to be
466.2150 (calcd. 466.2157). 2D NMR analysis confirms that the
two nitrogen atoms directly bound to the [2.2]paracyclophane
unit of 25 are disposed in a pseudo-para fashion. Unfortunately,
indole 25 proved to be unstable and we were not able to perform
any more analyses on it before it decomposed.
Compounds 24a and 24b both crystallize with imposed
inversion symmetry in space group P21/c with similar cell
constants; they are effectively isotypic.
Once pseudo-para bis(triazole) 24a was available, we
submitted a suspension of it in toluene to UV radiation. We
performed several experiments that lasted 4, 5, 6 and 10 h,
using the same TQ150 high pressure mercury vapor lamp. Each
time, the solvent was removed in vacuo. TLC analysis of the
reaction mixtures indicated the presence of some unreacted
substrate, together with five new compounds, as shown in
Scheme 8.
Compound 26 was identified as an amide. The 1H NMR
spectrum reveals the amide proton at 6.99 ppm, in the form of a
broad singlet. 2D NMR analysis, especially NOESY experiments,
pointed towards a pseudo-para substituted [2.2]paracyclophane.
It appears to be a stable compound that does not hydrolyze
during purification on silica gel.
When attempting to isolate derivative 27 using flash
chromatography on silica gel, we always obtained it as part of a
mixture with a different compound. However, when basic
alumina was employed, a pure sample of 27 was obtained.
Single crystals suitable for X-ray diffraction were obtained by the
slow diffusion of pentane into a chloroform solution of 27. The
results are presented in Figure 10.[23] The structure involves two
independent but closely similar molecules (a least-squares fit of
all non-H atoms led to an r.m.s. deviation of 0.15 Å). It seems
that compound 27 is hydrolyzed on contact with silica gel. TLC-
MS analysis indicated a compound with a molecular mass
corresponding to amine 29.
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N
H
N
N
N
A
N
N
H
H
N
N
N
N
N
N
28
25
N
H
N
N
N
B
Scheme 9. The formation of 28 from 25, via diradicals A and/or
B.
Figure 10. Molecular structure of compound 27 (two
independent molecules). Ellipsoids represent 30% probability
levels.[23]
1
The H NMR spectrum of 28 displays the nitrogen-bound indole
proton as a singlet at 8.48 ppm, while the triazole proton
appears as a singlet at 7.54 ppm. HRMS analysis of 28 revealed
a molecular mass of 466.2151, virtually identical to the recorded
value for indole 25.
The mechanism for the formation of derivatives 25-27
could be similar to the one presented in Scheme 5. Triazole 24a
first loses a molecule of nitrogen under UV-light, leading to the
formation of a carbene similar to structure 20. This, in turn, can
lead to the formation of an indole ring (derivatives 25 and 27), or
rearrange to a ketenimine which, upon workup hydrolyzes,
forming an amide (derivatives 26 and 27). It is worth noting that
for the indole-amide derivative 27, both initial triazole rings
suffered photolysis. As mentioned above, this was not observed
for pseudo-gem derivatives 18 and 19. This suggests that the
triazole ring in compounds 18 and 19 is stabilized by the indole
ring or amide function found in its proximity. This is no longer the
case for derivatives 25 and 26, where the photolysis of the
triazole ring clearly takes place, as evidenced by the formation
of indole-amide derivative 27.
The structure of indole 28 was also established through X-
ray analysis, after obtaining suitable single crystals by slow
diffusion of pentane into
a chloroform solution of 28.
Figure 11. Crystalline sample of compound 28, showing the
monoclinic polymorph (large blocks) and the orthorhombic
polymorph (fine needles).
Examination of the crystals under the microscope (Fig. 11)
showed two strikingly different types of crystal, large blocks and
fine needles; these proved to be two polymorphs of 28, one
monoclinic and one orthorhombic (Figure 12).[24] Both molecules
are closely similar except for the orientation of the phenyl rings;
a least-squares fit of all other atoms gave an r.m.s. deviation of
0.11 Å. The structure determinations show that the starting
triazole 24a has not only lost a molecule of nitrogen to form an
indole ring, but has also undergone conversion to the pseudo-
ortho isomer. It is known that under thermal[25,26] or
photochemical[27,28] conditions, one of the ethano bridges of the
[2.2]paracyclophane core can suffer homolysis, leading to the
formation of a diradical. By bond rotation of a benzene ring and
radical recombination, pseudo-para and pseudo-ortho isomers,
and also pseudo-gem and pseudo-meta isomers, are
interconvertible.[25] Thus, derivative 28 was probably formed
from indole 25 via one or both diradicals A, B presented in
Scheme 9. The presence of indole 28 in the reaction mixture
supports the theory that an indole ring in close proximity to a
triazole ring stabilizes the latter. While pseudo-para indole 25 is
unstable and decomposes, its isomer, pseudo-ortho indole 28 is
a stable compound.
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10.1002/chem.201701593
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Acknowledgements
L.M.B. is indebted to the Alexander von Humboldt Foundation
for a stay in Braunschweig. Part of this work has been supported
by a grant of the Romanian National Authority for Scientific
Research, CNDI– UEFISCDI, project number 152PED/2017.
Keywords: azides • click chemistry • [2.2]paracyclophane •
photochemistry • triazoles
[1]
[2]
C. J. Brown, A. C. Farthing, Nature 1949, 164, 915-916.
Modern Cyclophane Chemistry (Eds.: R. Gleiter, H. Hopf), Wiley-VCH,
Weinheim, 2004.
[3]
[4]
G. P. Bartholomew, G. C. Bazan, Acc. Chem. Res. 2001, 34, 30-39.
H. Hopf, Angew. Chem. 2008, 120, 9954-9958; Angew. Chem. Int. Ed.
2008, 47, 9808-9812.
[5]
[6]
L. Bondarenko, I. Dix, H. Hinrichs, H, Hopf, Synthesis 2004, 16, 2751–
2759.
a) I. Dix, L. Bondarenko, P. G. Jones, T. Oeser, H. Hopf, Beilstein J.
Org. Chem. 2014, 10, 2013–2020; b) H. Hopf, I. Dix, Synlett 2006, 9,
1416–1418; c) H. Hinrichs, A. J. Boydston, P. G. Jones, K. Kess, R.
Herges, M. M. Haley, H. Hopf, Chem. Eur. J. 2006, 12, 7103–7115.
L. Bondarenko, S. Hentschel, H. Greiving, J. Grunenberg, H. Hopf, I.
Dix, P. G. Jones, L. Ernst, Chem. Eur. J. 2007, 13, 3950 – 3963.
a) Y. Morisaki, Y. Chujo, Chem. Lett. 2012, 41, 840-846; b) Y. Morisaki,
R. Hifumi, L. Lin, K. Inoshita, Y. Chujo, Polym. Chem. 2012, 3, 2727–
2730; c) Y. Morisaki, S. Ueno, Y. Chujo, J. Polym. Sci. Pol. Chem. 2013,
51, 334–339; d) Y. Morisaki, M. Gon, Y. Chujo, J. Polym. Sci. Pol.
Chem. 2013, 51, 2311–2316; e) S. P. Jagtap, D. M. Collard, J. Am.
Chem. Soc. 2010, 132, 12208–12209.
[7]
[8]
Figure 12. Molecular structure of compound 28. Above,
monoclinic polymorph; below, orthorhombic polymorph.
Ellipsoids represent 50% probability levels.[24]
[9]
a) Y. Morisaki, K. Inoshita, Y. Chujo, Chem. Eur. J. 2014, 20, 8386–
8390; b) M. Gon, Y. Morisaki, Y. Chujo, Eur. J. Org. Chem. 2015,
7756–7762; c) M. Gon, Y. Morisaki, Y. Chujo, J. Mater. Chem. C 2015,
3, 521–529; d) M. Gon, Y. Morisaki, R. Sawada, Y. Chujo, Chem. Eur. J.
2016, 22, 2291–2298.
Conclusions
We have demonstrated with the respective model
compounds
that
both
mono-
and
disubstituted
ethynylcyclophanes 1, 2 and 5 and bis(azides) 9 and 10 can be
employed as addition partners in CuAAC reactions to design
and build complex extended molecular scaffolds. It seems likely
that 1,3-dipolar cycloadditions can also be performed with the
other oligo ethynyl cyclophanes listed in Fig. 1. Likewise, the
oligo azides corresponding to these alkynes should be
obtainable by the standard reactions used here.
This may mean that polyethynylated [2.2]paracyclophanes
and the corresponding azide derivatives can be used as
multivalent “molecular knots” or “superatoms” to construct new
molecular scaffolds with designed orientation of functional
groups in three-dimensional space. Of particular interest would
be cyclophane derivatives with more than four ethynyl or azido
substituents; these derivatives are presently unknown.
[10] R. J. Seacome, M. P. Coles, J. E. Glover, P. B. Hitchcock, G. J.
Rowlands, Dalton Trans. 2010, 39, 3687–3694.
[11] (a) M. Austeri, M. Enders, M. Nieger, S. Bräse, Eur. J. Org. Chem.
2013, 1667–1670; b) J. E. Glover, D. J. Martin, P. G. Plieger, G. J.
Rowlands, Eur. J. Org. Chem. 2013, 1671–1675; c) J. A. Griffith, J. M.
Withers, D. J. Martin, G. J. Rowlands, V. V. Filichev, RSC Adv. 2013, 3,
9373-9380.
[12] K. El Shaieb, V. Narayanan, H. Hopf, I. Dix, A. Fischer, P. G. Jones, L.
Ernst, K. Ibrom, Eur. J. Org. Chem. 2003, 567-577.
[13] S. Pavel, H. Hopf, P. G. Jones, I. V. Asaftei, L. G. Sarbu, L. M. Birsa,
Monatsh. Chem. 2016, 147, 2179–2183.
[14] D. Wang, M. Zhao, X. Liu, Y. Chen, N. Li, B. Chen, Org. Biomol. Chem.
2012, 10, 229-231.
[15] C. G. Bates, P. Saejueng, J. M. Murphy, D. Venkataraman, Org. Lett.
2002, 26, 4727-4729.
[16] CCDC-1513382
and
-1513383
contain
the
supplementary
Once the new adducts have been prepared and
characterized, they can be employed in further transformations.
Examples given here involve the photochemical deazotization of
adducts such as 15a and 25a. By these routes hitherto unknown
paracyclophane derivatives become available, such as the
indolophanes 26, 28, 29.
crystallographic data for compounds 12 and 13, respectively. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[17] CCDC-1513384
and
-1513385
contain
the
supplementary
crystallographic data for compounds 15a and 15b, respectively. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[18] CCDC-1513386 contains the supplementary crystallographic data for
compounds 17b. These data can be obtained free of charge from The
In summary, we believe that the approach described here,
which
involves
reaction
paths
starting
from
the
[2.2]paracyclophane nucleus and subsequently “moving out”
structurally provides a novel and potentially strongly variable
approach to complex molecular objects with a clearly defined
Cambridge
www.ccdc.cam.ac.uk/data_request/cif.
[19] CCDC-1513387 and -1513388
Crystallographic
Data
Centre
via
contain
the supplementary
crystallographic data for compounds 18 and 19, respectively. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
orientation of functional groups. In
[2.2]paracyclophane core functions as a “seed crystal” on which
the functional groups “grow” in specific orientation.
a
sense the
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10.1002/chem.201701593
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FULL PAPER
[20] a) S. M. C. Dietrich, R. O. Martin, J. Am. Chem. Soc. 1968, 90, 1923-
1924; b) T. L. Gilchrist, G. E. Gymer, C. W. Rees, J. Chem. Soc. Perkin
Trans. 1 1975, 1-8; c) G. Mitchell, C. W. Rees, J. Chem. Soc. Perkin
Trans. 1 1987, 413-422.
[21] CCDC-1513389 contains the supplementary crystallographic data for
compounds 10. These data can be obtained free of charge from The
Cambridge
www.ccdc.cam.ac.uk/data_request/cif.
[22] CCDC-1513390 and -1513391
Crystallographic
Data
Centre
via
contain
the supplementary
crystallographic data for compounds 24a and 24b, respectively. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[23] CCDC-1513394 contains the supplementary crystallographic data for
compounds 27. These data can be obtained free of charge from The
Cambridge
www.ccdc.cam.ac.uk/data_request/cif.
[24] CCDC-1513392 and -1513393
Crystallographic
Data
Centre
via
contain
the supplementary
crystallographic data for compound 28. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[25] H. J. Reich, D. J. Cram, J. Am. Chem. Soc. 1969, 91, 3517–3526.
[26] D. C. Braddock, S. M. Ahmad, G. T. Douglas, Tetrahedron Lett. 2004,
45, 6583-6585.
[27] G. Kaupp, E. Teufel, H. Hopf, Angew, Chem. 1979, 91, 232-234.
[28] R. Marquardt, W. Sander, T. Laue, H. Hopf, Liebigs, Ann. 1996, 2039-
2043.
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10.1002/chem.201701593
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Lucian G. Bahrin, Laura G. Sarbu, Peter
G. Jones, Lucian M. Birsa and Henning
Hopf*
N
N
N
Ph
H
N
N
N
Ph
pseudo-gem
Ph
N
h

h
H
pseudo-para
Ph
N
N
N
N
N
Page No. – Page No.
N
N
Ph
Ph
[2.2]Paracyclophane-Bis(triazole)
Systems: Synthesis and
Photochemical Behavior
Click reactions: Mono and disubstituted ethynylcyclophanes and azides have been
employed as addition partners in CuAAC reactions to build designed complex
extended molecular scaffolds. The resulting triazoles were investigated under
photochemical conditions. A variety of newly substituted [2.2]paracyclophanes were
identified; deazotation of pseudo-gem and pseudo-para adducts provided
indolophane derivatives.
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