Synthesis of substituted sumanenes by aromatic electrophilic substitution reactions

Article abstract of DOI:10.1246/cl.121273

Electrophilic substitution reactions of sumanene were studied. Mono-, di-, and trisubstituted sumanenes were selectively prepared with the separation of all regioisomers. The regioselectivity was predicted well by the HOMO density values determined by DFT

Full text of DOI:10.1246/cl.121273

doi:10.1246/cl.121273
386
Published on the web March 19, 2013
Synthesis of Substituted Sumanenes by Aromatic Electrophilic Substitution Reactions
Binod Babu Shrestha,1 Sangita Karanjit,1 Gautam Panda,2 Shuhei Higashibayashi,*1,2,3 and Hidehiro Sakurai*1,2
1Department of Functional Molecular Science, School of Physical Sciences, The Graduate University for Advanced Studies,
Myodaiji, Okazaki, Aichi 444-8787
2Research Center for Molecular Scale Nanoscience, Institute for Molecular Science, Myodaiji, Okazaki, Aichi 444-8787
3Japan Science and Technology Agency, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012
(Received December 26, 2012; CL-121273; E-mail: higashi@ims.ac.jp, hsakurai@ims.ac.jp)
O
R
Electrophilic substitution reactions of sumanene were
studied. Mono-, di-, and trisubstituted sumanenes were selec-
tively prepared with the separation of all regioisomers. The
regioselectivity was predicted well by the HOMO density values
determined by DFT calculations.
ref. 2
O
R
R
O
C3 symmetric
A
R+
R
The regioselective synthesis of aromatic compounds, in-
cluding sumanene derivatives, is very important in order to
explore their physical properties.1 For example, two sumanene
derivatives trisubstituted at the benzene rings, C3 symmetric and
unsymmetrical, are possible if ortho-substituted derivatives are
excluded. Previously, we developed the functionalization of C3
symmetric derivatives from precursor A (Scheme 1).2 However,
direct preparation of both isomers from sumanene (1)3 is also
beneficial if these isomers can be easily separated or one isomer
can be selectively obtained. A more complicated situation is
encountered in the case of disubstituted sumanene synthesis;
three possible isomers may be produced (Table 1).
Electrophilic aromatic substitution (SEAr) is one of the most
reliable methods for the direct functionalization of aromatic
compounds. However, due to the lack of regioselectivity and the
difficulty in separation of the regioisomers, the SEAr route has
rarely been applied to sumanene derivatization.4 The purpose of
this study involves the development of regioselective electro-
philic substitution reactions of sumanene, and prediction of their
regioselectivity by DFT calculations.
Sumanene (1)
R
R
unsymmetrical
Scheme 1.
R
2 (R = I) 75%
3 (R = NO2) 65%
4 (R = CHO) 60%
5 (R = COCH3) 64%
6 (R = COPh) 68%
conditions (ref. 5)
1
Scheme 2.5
Table 1. Synthesis of disubstituted sumanenes
R
R
R
R
Selective syntheses of monosubstituted sumanenes were
first investigated as summarized in Scheme 2.5 Iodosumanene
(2) was selectively prepared in 75% yield by AuCl3-catalyzed
iodination6 with N-iodosuccinimide (NIS) with recovery of 1.
Nitrosumanene (3) was obtained in 65% yield by nitration using
trifluoroacetyl nitrate, generated in situ from trifluoroacetic
anhydride and concd nitric acid.7 1 was completely consumed
and dinitrosumanenes were not formed. However, some amount
of degradation was observed due to the harsh conditions.
Formylation was achieved using triflic anhydride and DMF8
under microwave-assisted heating conditions to afford formyl-
sumanene (4) in 60% yield. Because of the low reactivity of the
reagent, high temperature (130 °C) was required to complete the
reaction. Although diformylsumanenes were also formed in 20%
yield with 4, these compounds were easily separated from 4 by
preparative thin layer chromatography (PTLC). Acetylation was
achieved by adopting similar conditions as the formylation in
the presence of DMA to afford acetylsumanene (5) in 64% yield
and diacetylsumanenes in 10% yield. Benzoylsumanene (6) was
also prepared in 68% yield using triflic acid and PhCOCl with
complete consumption of 1.9 They were easily purified by PTLC
as well.
+
+
1
R
a
c
b
R
Isolated yield/%
Compounds
a
b
c
7 (R = I)
8 (R = NO2)
9 (R = CHO)
10 (R = COCH3)
11 (R = COPh)
30
0
<1
5
15
27
20
10
26
23
30
25
25
41
0
The thus-employed reaction conditions were further applied
to the syntheses of disubstituted sumanenes (Table 1).10 Prep-
aration of diiodosumanenes 7, dinitrosumanenes 8, diformylsu-
manenes 9, diacetylsumanenes 10, and dibenzoylsumanenes 11
were achieved by increasing the amount of reagents. Diiodina-
tion of 1 afforded a mixture of three regioisomers, which were
successfully separated by gel permeation chromatography
(GPC) to give 7a (30%), 7b (15%), and 7c (23%).11 Isomer
Chem. Lett. 2013, 42, 386-388
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

387
I
CHO
NO2
(A)
1
1
1
2
3
2
2
6
5
0.0180
0.0117
6
5
6
5
0.0324
0.0074
0.0296
0.0140
2.88 Å
3.29 Å
0.0064
3
0.0416
3
0.0432
0.0000
4
0.0373
4
4
0.0018
3.42 Å
COCH3
COPh
1
1
2
2
6
6
5
0.0341
0.0389
0.0083
5
0.0076
0.0317
0.0015
3
3
0.0425
4
4
0.0024
Figure 1.
(B)
7a was the major product in the case of iodination. In contrast,
nitration, formylation, acetylation, and benzoylation showed
different regioselectivities from that of iodination. Dinitrosuma-
nenes 8b (27%), 8c (30%), diformylsumanenes 9b (20%), 9c
(25%), diacetylsumanenes 10a (5%), 10b (10%), 10c (25%), and
dibenzoylsumanenes 11b (26%), 11c (41%) were formed with
similar ratios of regioisomers.11 It should be pointed out that
these regioisomers of 8-11 were easily separated by PTLC.
Predictability of the regioselectivity is the key issue in
designing the reaction. Since different regioselectivities were
observed between iodination and other functionalizations, we
conducted DFT calculations [B3LYP/6-31G(d,p)] for monosub-
stituted sumanenes to determine Fukui function,12,13 HOMO
density,12,14 and spin density12 as shown in Table S6 (Support-
ing Information).20 Among the calculated parameters, the
HOMO density of monosubstituted sumanenes (Figure 1) is
consistent with the observed regioselectivity to give disubstitut-
ed sumanenes. In contrast, Fukui function and spin density are
not consistent with the observed regioselectivities. This may be
due to soft nature of bowl-shaped polyaromatic hydrocarbon. In
this case, orbital contribution (HOMO density) predominated
over charge contribution (Fukui function).13b
3.71 Å
3.63 Å
3.71 Å
3.63 Å
Figure 2. ORTEP drawings of (A) 7b and (B) 10b with 50%
probability ellipsoids.
R
R
1
+
R
R
R
b
a
R
R = I
R = COPh
14% (12a)
28% (13a)
71% (12b)
30% (13b)
Scheme 3.
Single crystals of 7b and 10b for X-ray crystallographic
analysis were obtained by crystallization from CHCl3 and THF,
respectively.15 Their packing structures are shown in Figure 2.
The bowl depth of 7b is 1.18 ¡, which is deeper than those
of sumanene (1.11 ¡)16 and trimethylsumanene (1.11 ¡).2c In
contrast, 10b shows a more shallow bowl depth (1.10 ¡). The
packing structure of 7b adopts a quasi convex-convex and
concave-concave stacking model, which is similar to that of
tris(methylsulfonyl)triazasumanene.17 At the convex face, the
benzylic exo-hydrogens and the non-iodinated benzene rings of
two molecules are located within the distance (2.88 ¡) of CH-³
interaction. The benzene rings substituted by iodine are also
stacked at a distance of 3.29 ¡ at the convex face. At the
concave face, the iodine atoms face the central benzene ring of
the bowl structure at a distance of 3.42 ¡. Similar interactions
between the oxygen atoms of the sulfonyl groups and the central
benzene rings at the concave face are observed in the crystal
packing of tris(methylsulfonyl)triazasumanene.17 These two
examples may suggest a lone pair-³ interaction between iodine
or oxygen and the bowl at the concave face.18 On the other hand,
10b adopts a convex-concave stacking model with neighboring
columns in opposite directions, which is similar to that of
trimethylsumanene.2c However, the bowls of 10b in a column
are slipped from side to side, while those of sumanene and
trimethylsumanene are not. As a result of the slipping, the
convex faces of a central benzene ring and a peripheral benzene
ring with an acetyl group stack with the concave faces of
peripheral benzene rings with and without acetyl groups with
distances of 3.71 and 3.63 ¡, respectively.
Finally, syntheses of trisubstituted sumanenes are demon-
strated in Scheme 3.19 Triiodosumanenes 12a and 12b were
obtained in 14% yield and 71% yield, respectively, after
separation by GPC.11 Unsymmetrical 12b was formed as the
major isomer of iodination. In contrast, tribenzoylation afforded
13a in 28% yield and 13b in 30% yield.11 The regioisomers of
12 and 13 were separable by GPC. As observed in disubstituted
sumanenes, different regioselectivities between iodination and
benzoylation were observed in trisubstituted sumanenes as well.
The regioselectivity is also explained well by the HOMO
densities of disubstituted sumanenes (Figure 3). Since diiodo-
sumanenes 7a and 7b were converted to only triiodosumanene
12b, the selectivity of 7c to 12a and 12b was examined. The
lower HOMO density of 7c at C5 (0.0002) compared to C6
(0.0429) leads to less formation of 12a, which agrees with the
Chem. Lett. 2013, 42, 386-388
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

388
I
COPh
¹10 °C, 0.5 h; R = CHO, (CF3SO2)2O (1000 mol %), DMF
(1000 mol %), CH2ClCH2Cl, Microwave, 130 °C, 3 h; R =
COCH3, (CF3SO2)2O (500 mol %), DMA (500 mol %), CH2-
ClCH2Cl, Microwave, 130 °C, 3 h; R = COPh, CF3SO3H
(500 mol %), PhCOCl (250 mol %), CH2ClCH2Cl, ¹40 °C,
0.5 h, 80 °C, 1 h.
1
1
2
2
6
5
0.0429
0.0002
6
5
0.0189
0.0296
3
3
I
COPh
4
4
7c
11c
6
a) F. Mo, J. M. Yan, D. Qiu, F. Li, Y. Zhang, J. Wang,
Angew. Chem., Int. Ed. 2010, 49, 2028. b) B. Topolinski,
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Figure 3.
experimental results. On the other hand, the higher HOMO
density of 11c at C5 (0.0296) compared to C6 (0.0189) causes
greater formation of 13a. The sum of the conversion from 11b to
13b and 11c to 13a and 13b afford the observed fair yield of 13a
and 13b.
In summary, we have succeeded in the selective preparation
of mono-, di-, and trisubstituted sumanenes from sumanene and
the separation of regioisomers by employing SEAr reactions:
iodination, nitration, formylation, acetylation, and benzoylation.
The observed regioselectivities for di- and trisubstituted suma-
nenes were explained well by the HOMO densities calculated by
the DFT method. In order to study the physical properties of
sumanene derivatives with various substituents, these prepared
compounds are useful precursors for further transformation.
They could also be potential components for synthesizing three-
dimensionally ³-conjugated compounds.
7
8
9
10 Conditions (for disubstitution): R = I, AuCl3 (30 mol %),
NIS (300 mol %), CH2ClCH2Cl, rt, 1 h; R = NO2,
(CF3CO)2O (500 mol %), 60% HNO3 (500 mol %), CH2Cl2,
¹10 °C, 1 h, rt, 6 h; R = CHO, (CF3SO2)2O (5000 mol %),
DMF (5000 mol %), CH2ClCH2Cl, Microwave, 130 °C, 3 h;
R = COCH3, (CF3SO2)2O (2500 mol %), DMA (2500
mol %), CH2ClCH2Cl, Microwave, 130 °C, 3 h; R = COPh,
CF3SO3H (1000 mol %), PhCOCl (500 mol %), CH2ClCH2-
Cl, ¹40 °C, 0.5 h, 80 °C, 2 h.
This work was funded by MEXT and JST (ACT-C). B. B. S.
thanks the Daiko Foundation for financial support. G.P.
acknowledges the support from JSPS as a long-term Invitation
Fellowship Program from Central Drug Research Institute,
India. We thank Ms. Sachiko Nakano for technical contributions.
11 The regioisomers were assigned by NMR and X-ray
analysis. See the Supporting Information for details.20
12 a) R. K. Roy, S. Saha, Annu. Rep. Prog. Chem., Sect. C:
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Comput. 2010, 6, 1470. b) P. Geerlings, F. De Proft, W.
Langenaeker, Chem. Rev. 2003, 103, 1793.
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2
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15 See Supporting Information for details.20
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3
4
H. Sakurai, T. Daiko, T. Hirao, Science 2003, 301, 1878.
a) T. Amaya, S. Seki, T. Moriuchi, K. Nakamoto, T. Nakata,
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19 Conditions (for trisubstitution): R = I, AuCl3 (30 mol %),
NIS (500 mol %), CH2ClCH2Cl, rt, 1 h; R = COPh, CF3-
SO3H (1000 mol %), PhCOCl (1000 mol %), CH2ClCH2Cl,
¹40 °C, 0.5 h, 80 °C, 2 h.
5
Conditions (for monosubstitution): R = I, AuCl3 (10 mol %),
NIS (120 mol %), CH2ClCH2Cl, rt, 22 h; R = NO2,
(CF3CO)2O (200 mol %), 60% HNO3 (200 mol %), CH2Cl2,
20 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2013, 42, 386-388
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/