Synthesis of sterically crowded 9-nitrotriptycenes by the Diels–Alder cycloaddition reaction

Article abstract of DOI:10.1016/j.tetlet.2016.10.041

The synthesis of novel sterically crowded triptycenes as attractive components for the construction of models for various molecular dynamic studies is reported. 9-Nitrotriptycenes were obtained by the Diels–Alder reactions between 9-nitroanthracene and tetrabromobenzyne as well as 1,4-dichloro-9-nitroanthracene and 2,6-dichlorobenzyne. Interesting regioselectivity relative to the central and terminal rings was observed. Moreover, 1,2,3,4-tetrabromo-9-nitrotriptycene was further functionalized to afford 1,2,3,4-tetrabromotriptycyl-9-ammonium tetrafluoroborate in two-steps. The impact of steric hindrance on the geometry of the molecule was estimated on the basis of single crystal X-ray diffraction data.

Full text of DOI:10.1016/j.tetlet.2016.10.041

Tetrahedron Letters xxx (2016) xxx–xxx
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Tetrahedron Letters
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Synthesis of sterically crowded 9-nitrotriptycenes by the Diels–Alder
cycloaddition reaction
Artur Szupiluk
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of novel sterically crowded triptycenes as attractive components for the construction of
models for various molecular dynamic studies is reported. 9-Nitrotriptycenes were obtained by the
Diels–Alder reactions between 9-nitroanthracene and tetrabromobenzyne as well as 1,4-dichloro-9-
nitroanthracene and 2,6-dichlorobenzyne. Interesting regioselectivity relative to the central and terminal
rings was observed. Moreover, 1,2,3,4-tetrabromo-9-nitrotriptycene was further functionalized to afford
1,2,3,4-tetrabromotriptycyl-9-ammonium tetrafluoroborate in two-steps. The impact of steric hindrance
on the geometry of the molecule was estimated on the basis of single crystal X-ray diffraction data.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 17 August 2016
Revised 30 September 2016
Accepted 12 October 2016
Available online xxxx
Keywords:
Triptycenes
Diels–Alder reaction
Sterically crowded compounds
Introduction
R2
R2
Triptycene (9,10-dihydro-9,10[10,20]-benzenoanthracene) deriva-
tives are an important class of organic compounds due to their struc-
tural properties. These compounds have proven to be useful in many
areas of chemistry, e.g., in materials and supramolecular chemistry,1
as molecular rotors, and as models for the study of hindered rota-
tion2 including non-classical effects on the dynamics of methyl
groups.3 Because of the simple functionalization of the nitro group,
nitrotriptycenes and other similar bicyclic nitro compounds are an
interesting group of molecules for the construction of models to
study hindered rotation (Scheme 1).
R1
R1
R2
R2
NH
O
R1
R1
R1
R1
R1
R1
R1
R1
HN
O
NO2
R1
R1
However, reports on the synthesis of triptycene derivatives
from electron-poor anthracene derivatives are scarce. Reported
routes involve the Diels–Alder reaction of 9-nitro,1e,4a,b,5,6
9-carbonyl,4c–h and 9-nitrile4b,i,j,5 anthracene derivatives with
benzyne4–6 or alkyl1e,4a,b,f,h benzyne derivatives. Examples of the
Diels–Alder reaction leading to sterically crowded triptycenes
substituted at position 9 by an electron-withdrawing group and
by similar groups, e.g., halogens, in the peri positions, are not
found in the literature. In such compounds, steric effects exerted
by the halogen atoms are easily modelled using quantum
chemistry methods. Because the relevant molecular fragments
are rigid, extra computational efforts to treat the flexibility issue
are spared.
R2
R2
Scheme 1. An example of the application of a 9-nitrotriptycene derivative for the
construction of molecular devices executing temperature-controlled rotational and
vibrational motions.1e
Results and discussion
Reported literature methods for performing the Diels–Alder
reaction between electron-deficient anthracenes and benzynes,
involve thermal decomposition of the benzyne precursors, added
as
a
suspension.1e,6 In order to obtain one of the two
9-nitrotriptycene derivatives reported herein, these methods had
to be adapted to the specific properties of the precursor. The
choice of the counter-anion in the latter was proven critical in
this respect. Three side-products of the cycloaddition reactions
E-mail address: aszupiluk@icho.edu.pl
http://dx.doi.org/10.1016/j.tetlet.2016.10.041
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Szupiluk, A. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.10.041

2
A. Szupiluk / Tetrahedron Letters xxx (2016) xxx–xxx
were also identified. Including these, total yields of 62% and 91%
were obtained. The considerable yields of the side-products
confirm the significance of steric and electronic effects for the
regioselectivity of the discussed reaction.
IR
O
OH
Cl
Cl
NO2
Cl
Cl
N
The cycloaddition reaction between 9-nitroanthracene 5 and
tetrabromobenzyne was performed via generation of the latter
by thermal decomposition of 2-carboxytetrabromodiazonium
tetrafluoroborate 4 (Scheme 2). Three cycloadducts, 6, 7 and 8, in
a ratio of 3:1:0.5, respectively, were obtained, as determined by
NMR spectroscopy (91% conversion). This regioselectivity was pos-
tulated to be caused by a steric interaction between the halogen
substituent of the aryne derivatives and the nitro group of
9-nitroanthracene and/or the lower reactivity of the central ring
of the anthracene system.
Nitration
SiO2
Nu
H
12a
Nu = OH
1H NMR, IR
NO2 12b
MS
Scheme 3. Proposed transient structures observed in the nitration reaction with
nitrogen oxide.
Nitrotriptycene 16 was obtained via the cycloaddition reaction
between 1,4-dichloro-9-nitroanthracene 12 and 3,6-dichloro-2-
carboxybenzenodiazonium chloride 14 as the benzyne precursor
(Scheme 4). Compound 12 was obtained via a four-step synthesis.
The AlCl3 catalysed Friedel–Crafts reaction of phthalic anhydride 9
with 1,4-dichlorobenzene yielded the corresponding keto-acid
which was treated with concentrated sulfuric acid to afford
1,4-dichloroanthraquinone 10. After reduction under basic condi-
tions according to a literature procedure,10 1,4-dichloroanthracene
11 was obtained in 55% yield. The synthesis of 12 was troublesome,
due to the high reactivity of 1,4-dichloro-9-nitroanthracene
towards the oxidising reagent. In the nitration reaction of 11 with
HNO3/H2SO4 in acetic acid only 1,4-dichloroanthraquinone was
observed, which was consistent with literature reports.11 Com-
pound 12 could be obtained in low yields (8%) under milder condi-
tions (1,2-dichloroethane/35% HNO3 aq, 60 °C), despite complete
conversion. A satisfactory yield was achieved using nitrogen oxide
as the nitration reagent. However, in the 1H NMR spectra of the
crude reaction mixture (ESI) the characteristic signals of product
12 could not be identified. Instead, two strong singlets at 7.13
and 6.93 ppm were observed. In the MS (ESI) spectra, two signals
at m/z = 332.1 and 360.4 (M+Na) were present. In the IR spectra,
two characteristic absorptions at 2961–2853 cmꢀ1 and
O
Cl
Cl
O
a, b
O
10%
O
O
10
9
Cl
Cl
c
55%
11
d, e
Cl
Cl
NO2
Cl
Cl
15%
46%
f
NO2 Cl
15
15;16, 1.6:1
Cl
Cl
Cl
12
Cl
Cl
O
Cl
Cl
O
14%
NO2
g
Cl
OH
NH2
OH
N2+ Cl-
16
Cl
Br
Br
O
Br
Br
Br
Br
NH2
OH
a, b
13
14
O
50%
Scheme 4. Synthesis of 1,4-dichloro-9-nitroanthracene and the cycloaddition
reaction with 2,5-dichlorobenzyne. Reagents and conditions: (a)9 1,4-Dichloroben-
zene, AlCl3, 120 °C; (b) H2SO4, 100 °C; (c)10 Zn, NH3/H2O, 0–75 °C, (d) dichlor-
omethane, N2O5, rt, (e) SiO2; (f) 1,2-dichloroethane, reflux, (g)1e iso-pentyl nitrite,
EtOH, HClaq, 0 °C, Et2O.
O
Br
Br
O
1
3
c
NO2
Br
Br
Br
O
Br
Br
Br
Br
1557 cmꢀ1 were observed. The above NMR, MS and IR data were
consistent with the transient structures 12a and 12b (Scheme 3).
During the course of purification by silica gel chromatography,
these must have been converted into compound 12, which was
finally isolated in 46% yield.
37%
OH
4
N2+ BF4
-
6
Br
Br
Br
Br
NO2
Br
In the next step, the cycloaddition reaction between 12 and 14
was carried out. Two cycloadducts were observed, 16 and 15 in a
ratio of 1:1.6, respectively, as determined by NMR spectroscopy
(62% conversion).
A suitable single crystal for X-ray diffraction measurements on
the sterically crowded triptycenes was obtained for the ammo-
7%
d
6:7:8, 3:1:0.5
NO2
5
7
8
Br
NO2
Br
Br
Br
Br
Br
Br
nium salt 18, obtained by functionalization of compound
7
<1%
(Scheme 5).
Compound 18 (Fig. 1) crystallizes in the orthorhombic P 21 21 21
space group. The position of the NH3 group and specific interac-
tions shows the influence of the hindered environment on this
group. The ammonium protons may form so called blue-shifting
hydrogen bonds with the bromine atom (Fig. 1), by analogy with
Br
Scheme 2. Synthesis of 6, 7 and 8. Reagents and conditions: (a)7 NH3 aq, DMSO, rt.;
(b) Br2/NaOHaq 0 °C; (d) 1,2-
0–80 °C, (c)8 iso-pentyl nitrite, Et2O, HBF4
dichloroethane, reflux. For 8 only one stereoisomer was obtained, however, its
stereochemistry (cis or trans) could not be determined.
,
,
aq
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A. Szupiluk / Tetrahedron Letters xxx (2016) xxx–xxx
3
Br
Br
Br
Br
Br
Br
Br
Acknowledgments
The author would like to acknowledge Prof. A. Szumna, Prof.
Br
Br
Br
Br
Br
a
b
´
B. Korybut-Daszkiewicz and Dr. C. Wisniewska for constructive
70 %
69%
discussions. This work was supported by the National Science
Center (grant OPUS-2012/05/B/ST4/00103).
NH2
NH3
BF4
NO2
-
7
17
18
Supplementary data
Scheme 5. Synthesis of 1,2,3,4-tetrabromotriptycyl-9-ammonium tetrafluorobo-
rate. Reagents and conditions: (a) SnCl2/HCl, propionic acid, reflux; (b) HBF4ꢁEt2O,
CH2Cl2, rt.
Supplementary data (general procedures, experimental proce-
dures and compound characterization: 1H NMR, 13C NMR and mass
spectra of compounds 3–17. 1H NMR, 19F NMR and single crystal
X-ray data for compound 18 (CCDC 1448445). 1H NMR spectra of
the cycloaddition reactions. 1H NMR and IR spectra of the nitration
reaction) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2016.10.041.
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Figure 1. Single crystal X-ray structure (ORTEP) of compound 18.
the methyl protons in the methyl analogue of 18.12 Br1 was bent
out of the plane of the ring. This appears to be the most significant
manifestation of the steric hindrance in 18. Namely, the torsion
angle in the sequence Br1-C2-C1-C14 amounts to ꢀ14.1 deg, for
comparison, in the Br4-C5-C6-C7 arrangement the torsion angle
was only 1.31 deg.
Conclusion
In summary, the synthesis of new sterically crowded bicyclic
compounds via cycloaddition reactions between deactivated
anthracene systems and substituted arynes was described. Func-
tionalization of one of the newly obtained compounds was carried
out yielding 1,2,3,4-tetrabromotriptycyl-9-ammonium tetrafluo-
roborate, an ammonium salt with the ammonium group placed
in extremely crowded environment. Some steric hindrance effects
in the latter compound were discussed on the basis of its single
crystal X-ray structure.
Please cite this article in press as: Szupiluk, A. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.10.041