Facile multistep synthesis of isotruxene and isotruxenone

Article abstract of DOI:10.1021/jo900299q

(Chemical Equation Presented) Three multistep approaches toward facile syntheses of isotruxene (1) and isotruxenone (3) are reported. The ortho-para conjugated backbone in the precursor 4 was constructed by either Co-catalyzed [2 + 2 + 2] cyclotrimerization or the [4 + 2] Diels-Alder reactions. The regioselectivity of the triple intramolecular Friedel-Crafts acylation of 4 plays the key role in determining the overall yield. Compared to the previous one-step method, the current approaches are more efficient in terms of product yield (27-36% vs 4-18%) and purification (i.e., free of column chromatography).

Full text of DOI:10.1021/jo900299q

recently revealed that the star-shaped isotruxene-oligofluorene
hybrids demand a lower oxidation potential for generating the
hole carrier and shorter π-conjugated backbone for achieving
blue emission than the truxene-oligofluorene counterparts.4
However, unlike the well-documented truxene derivatives,5,7-9
the corresponding isotruxene chemistry is much less explored.3,4
One of the most important origins could be ascribed to the
poorly developed synthesis of isotruxene building blocks,
including the parent isotruxene 1 and the isotruxenone 3. Both
of the two currently known methods for the preparation of 1
are the cyclotrimerization of indene.3,10 The reactions suffer
from either the requirement of a harsh condition (20 atm and
350 °C)10 or the limitation of a small reaction scale (∼10
mmol).3 Even worse are the low yields (∼18%) and the
difficulties of product purification (i.e., by column chromatog-
raphy with extreme care or small quantity). The subsequent
synthesis of 3 from the oxidation of 1 by CrO3 was also reported
to be of low yield (21%).10 To circumvent these problems, we
have devised new methodologies toward facile synthesis of 1
and 3, i.e., through the precursors 4a or 4b (Scheme 1). Our
results reported herein significantly improve the yields and
reduce the efforts in product purification.
Facile Multistep Synthesis of Isotruxene and
Isotruxenone†
Jye-Shane Yang,* Hsin-Hau Huang, and Shih-Hsun Lin
Department of Chemistry, National Taiwan UniVersity,
Taipei, Taiwan 10617
jsyang@ntu.edu.tw
ReceiVed February 10, 2009
Three multistep approaches toward facile syntheses of
isotruxene (1) and isotruxenone (3) are reported. The
ortho-para conjugated backbone in the precursor 4 was
constructed by either Co-catalyzed [2 + 2 + 2] cyclotri-
merization or the [4 + 2] Diels-Alder reactions. The regio-
selectivity of the triple intramolecular Friedel-Crafts acy-
lation of 4 plays the key role in determining the overall yield.
Compared to the previous one-step method, the current
approaches are more efficient in terms of product yield
(27-36% vs 4-18%) and purification (i.e., free of column
chromatography).
SCHEME 1
Isotruxene (1) is an isomer of truxene (2), and they differ in
the arrangement, and thus the conjugation interactions, of the
phenylene groups: namely, the peripheral phenylenes are
ortho-para conjugated with respect to the central ring in 1, it
is meta-meta conjugated in 2. Since the ortho and para
conjugation interactions are inherently stronger than the meta
one, the planar isotruxene scaffold is a potential phenylene-
based branching unit for the development of new hyper-
branched,1 star-shaped,2-5 and dendritic6,7 π-conjugated systems
of strong interbranch electronic couplings. For example, we
To construct the ortho-para π-conjugated backbone with the
desired carboxylic acid or ester substituents shown in 4, our
(5) (a) Pei, J.; Wang, J.-L.; Cao, X.-Y.; Zhou, X.-H.; Zhang, W.-B. J. Am.
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126, 13695–13702. (c) Sun, Y. M.; Xiao, K.; Liu, Y. Q.; Wang, J. L.; Pei, J.;
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† This paper is dedicated to Prof. Kwang-Ting Liu on the occasion of his
70th birthday.
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3974 J. Org. Chem. 2009, 74, 3974–3977
10.1021/jo900299q CCC: $40.75 2009 American Chemical Society
Published on Web 04/09/2009

SCHEME 2
TABLE 1. Temperature Effect on the Yield of 3 and the Reaction
Time for the Triple Intramolecular Friedel-Crafts Acylation of 4a
SCHEME 3
entry
temperature (°C)
time (min)
yield (%)
1
2
3
4
5
25
60
80
140
160
180
120
120
5
0
20
27
40
40
5
first approach is to adopt the protocol of Co-catalyzed [2 + 2
+ 2]-cyclotrimerization of alkynes.11 As shown in Scheme 2,
we used the commercially available 1-phenylpropyne (5) for
this purpose. The regioselective cyclotrimerization of 5 has been
previously reported,11 namely, the desired ortho-para system
6 is the major product (86%), and the meta-meta derivative 7
is a minor one (not isolated). Oxidation of the methyl groups
of 6 with potassium permanganate in aqueous pyridine afforded
4a with a high yield (90%). It should be noted that an attempt
to construct the scaffold of 4b in one step through the same
[2 + 2 + 2]-cyclotrimerization method directly with ethyl
phenylpropiolate (8) was unsuccessful. For the subsequent
conversion of 4a f 3,12 the yield is strongly temperature-
dependent. As shown in Table 1, the yield increases and the
reaction time decreases with raising the reaction temperature
from 25 to 140 °C. No further increase of the yield was found
at 160 °C. This can be rationalized by the competing side
reaction shown in Scheme 3. As compared to phenyl ring A,
phenyl rings B and C are expected to be less coplanar with the
central ring due to larger steric hindrance. Consequently, the
electrophilic addition of carboxylic acid group c to phenyl ring
A should be more favorable than to ring C and thus lead to the
formation of 9 (25 °C, 65% yield). However, such a preference
is reduced upon raising the temperature, presumably due to the
increased torsional fluxions of phenyl ring A. The observed 40%
yield for 3 from 4a is close to the theoretical 50% yield for a
nonselective attack of carboxylic acid group c toward phenyl
ring C vs A. The isotruxene scaffold 1 was then accomplished
by the Wolf-Kishner reduction of 3 in a yield of 91%. The
overall yield of 1 with the four-step method shown in Scheme
2 is 28%, which is increased by more than 50% as compared
to the previous one-step method (18%). More importantly, there
is no need of column chromatography in product purification
for all the steps, which is a merit for large-scale practice (e.g.,
20 g).
Despite the significant improvement of the synthesis of 1 and
3 outlined in Scheme 2, one potential problem emerges in their
subsequent derivatization. We have sometimes found contami-
nation of a trace amount of truxene-based isomers that is
undetectable with NMR but detectable with fluorescence spec-
troscopies in the final isotruxene-based π-conjugated materials.
The contamination, albeit in a trace amount, is hardly removed
and could cause severe interference in the photophysical studies.
This phenomenon suggests that the precursor 6 is already
contaminated with the isomer 7, which might not be readily
1
recognized based on H and 13C NMR spectroscopies. More
specifically, the three chemically nonequivalent methyl groups
in 6 display only two proton resonance peaks at 2.06 and 1.73
ppm with a 2:1 ratio. The signal of the methyl groups in 7
happens to overlap with the peak of 6 at 1.73 ppm. Thus, within
the experimental error of peak integration, the presence of a
small quantity of 7 in 6 would be hardly ascertained. Figure 1a
shows one such example. The intensity ratio of the 2.06 to 1.73
ppm signal in this sample is very close to 2 (1.91), and it was
later shown to be contaminated. For comparison, Figure 1b
shows the corresponding region of 1H NMR spectrum for
another sample prepared using a less-selective palladium
catalyst.13 According to the integration, the ratio of 6/7 is ca.
(9) (a) Duan, X.-F.; Wang, J.-L.; Pei, J. Org. Lett. 2005, 7, 4071–4074. (b)
Kimura, M.; Kuwano, S.; Sawaki, Y.; Fujikawa, H.; Noda, K.; Taga, Y.; Takagi,
K. J. Mater. Chem. 2005, 15, 2393–2398. (c) Wang, J.-L.; Luo, J.; Liu, L.-H.;
Zhou, Q.-F.; Ma, Y.; Pei, J. Org. Lett. 2006, 8, 2281–2284. (d) Sa´nchez, L.;
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Chem. Mater. 2006, 18, 4259–4269. (f) Yuan, M.-S.; Liu, Z.-Q.; Fang, Q. J.
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325.
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1475.
(12) Although 3 is a known compound, its NMR spectra are unknown. The
1H NMR spectrum of 3 is provided in the Supporting Information, but due to its
poor solubility, the corresponding 13C NMR spectrum is not determined.
(13) Li, J.; Jiang, H.; Chen, M. J. Org. Chem. 2001, 66, 3627–3629.
J. Org. Chem. Vol. 74, No. 10, 2009 3975

SCHEME 4
SCHEME 5
3:1. As shown in Figure 1c and d, similar situation is also present
in their 13C NMR spectra: namely, the signal of the methyl
groups in 7 (19.6 ppm) overlaps with one of the three methyl
signals of 6 (19.6, 18.4, and 18.2 ppm). While this problem
could be resolved by integration with careful baseline correction
along with multiple recrystallization of the product 6, we decided
to explore alternative synthetic strategies that provide only the
desired π-conjugated pattern.
nylcyclopentadienone 10 and ethyl 3-phenylpropiolate (8). The
starting material 10 was in turn prepared according to the
literature procedures from diethyl 1,3-acetonedicarboxylate and
benzil.14 As is the condition for the transformation of 4a f 3,
compound 4b could be directly converted to 3 with the same
yield (40%). Compared to the first approach (Scheme 2), this
one adds one more step toward the isotruxenone 3 (4 steps)
and isotruxene 1 (5 steps). Nonetheless, the overall yield is
essentially the same (31% vs 30% and 28% vs 27%, respec-
tively). Like the first approach, there is no need of column
chromatography for product purification in all these steps. More
importantly, the purification of the products is rather straight-
forward and it is free of contamination of hardly recognized
side products toward 1 and 3.
As shown in Scheme 4, the scaffold of 4b can be constructed
through the Diels-Alder reaction of the diethoxycarbonyldiphe-
The intramolecular Friedel-Crafts acylation of 4 f 3 is a
common step for both the first (Scheme 2) and the second
(Scheme 4) approaches toward the synthesis of 1 and 3. Because
of the unfavorable regiochemistry, this step is also responsible
for the low yield of the final products.
To circumvent the undesired side reaction shown in Scheme
3, we have carried out the third approach by modifying the
second one. As shown in Scheme 5, a replacement of diethyl
1,3-acetonedicarboxylate with 3-pentanone for the condensation
reaction with benzil leads to the dimethyldiphenylcyclopenta-
dienone 11, which exists as a dimer at room temperature.15 The
subsequent Diels-Alder reaction with 8 provides the monoester
12, which undergoes single Friedel-Crafts acylation to form
13 in hot polyphosphoric acid. The two methyl groups were
then oxidized to provide 14 in a way similar to that for 6 f 4a
(Scheme 2). The subsequent double Friedel-Crafts acylation
will lead to the desired product 3 without the complication of
1
FIGURE 1. Comparison of the H (a and b) and 13C (c and d) NMR
spectra (CDCl3) of two samples of 6 containing a small (a and c) and
significant amount (b and d) of 7.The mark × denotes the signal of
H2O.
(14) White, D. M. J. Org. Chem. 1974, 39, 1951–1952.
(15) Allen, C. F. H.; VanAllan, J. A. J. Am. Chem. Soc. 1950, 72, 5165–
5167.
3976 J. Org. Chem. Vol. 74, No. 10, 2009

washed with water and brine, and the CH2Cl2 solvent was removed
under reduced pressure. The crude product was recrystallized from
CHCl3/MeOH to afford the orange solid of isotruxenone with a
yield of 40%. (b) From Compound 14: In a 250 mL round-bottom
flask was added 100 mL of concd H2SO4 (17.7 M) and heated to
70 °C under stirring. A batch of 10.0 g of a powder of compound
14 (23.7 mmol) was then added and the mixture was kept at 70 °C
for 3 h. After cooling to room temperature, the solution was poured
into ice. The mixture was extracted with CH2Cl2. The organic layer
was washed with water and brine, and the CH2Cl2 solvent was
removed under reduced pressure. The crude product was recrystal-
lized from CHCl3/MeOH to afford the orange solid of isotruxenone
regiochemistry. Although this “regio-controlled” approach
lengthens the synthetic route by two more steps (i.e., 6 steps to
3), the overall yield of 3 is higher than that of the previous two
approaches (40% vs 30%).
In summary, we have developed three different facile
synthetic approaches toward isotruxene (1) and isotruxenone
(3). Although the synthesis of 1 requires 4-7 steps, none of
the steps requires the use of column chromatography for product
purification and the overall yields are all higher than the previous
one-step methods. Our results should facilitate the development
of isotruxene-based materials.
with a yield of 78%. mp ) 318-320 °C (lit.10 317-318 °C); H
1
NMR (400 MHz, CDCl3) 7.40-7.48 (m, 3H), 7.59-7.65 (m, 3H),
7.72-7.80 (m, 3H), 8.08 (d, J ) 7.6 Hz, 1H), 8.15 (d, J ) 8.0 Hz,
1H), 9.03 (d, J ) 7.6 Hz, 1H) ppm.
Experimental Section
Three key synthetic steps, which for the preparation of com-
pounds 1, 3, and 4b are described in the following text, and the
synthesis and characterization data of 4a, 6, 9, and 12-14 are
presented in the Supporting Information.
Synthesis of Compound 4b. A mixture of 10 (10.0 g, 26.5
mmol) and 8 (5.00 g, 28.7 mmol) in a 50 mL tube was sealed and
then heated to 180 °C for 24 h. After being cooled to room
temperature, the crude product was recrystallized from ether to
afford the white solid of 4b with a yield of 76%. mp ) 154-156
Synthesis of Isotruxene (1) from Isotruxenone (3). The
isotruxenone 3 (9.00 g, 23.4 mmol) was suspended in diethylene
glycol (450 mL) containing KOH (45.0 g, 802 mmol). Hydrazine
monohydrate (25.0 g, 1.32 mol) was added. The mixture was heated
at 180 °C for 24 h and then cooled to ca. 60 °C. The warm solution
was poured into ice containing HCl. The precipitate was filtered,
washed with H2O, and dried. The precipitate was then dissolved in
CH2Cl2 and passed through a thin layer of silica gel. The CH2Cl2
solvent was then removed under reduced pressure and the crude
product was recrystallized from CHCl3/MeOH to afford the white
solid of isotruxene with a yield of 91%. mp ) 218-220 °C (lit.3
218-220 °C); 1H NMR (400 MHz, CDCl3): 3.99 (s, 4H), 4.25 (s,
2H), 7.31-7.39 (m, 3H), 7.43-7.50 (m, 3H), 7.59-7.63 (m, 2H),
7.67 (d, J ) 7.2 Hz, 1H), 7.91 (d, J ) 7.2 Hz, 1H), 8.58 (t, J ) 8.4
Hz, 2H) ppm.
Synthesis of Isotruxenone (3). (a) From Compounds 4a or 4b:
In a 250 mL round-bottom flask was added 100 mL of concd H2SO4
(17.7 M) and heated to 140 °C under stirring. A batch of 10.0 g of
a powder of compound 4a (22.8 mmol) or 4b (19.1 mmol) was
then added, and the mixture was kept at 140 °C for 5 min. After
being cooled to room temperature, the solution was poured into
ice. The mixture was extracted with CH2Cl2. The organic layer was
°C (lit.16 157-158 °C); H NMR (400 MHz, CDCl3) 0.67 (t, J )
1
7.6 Hz, 3H), 0.84-0.91 (m, 6H), 3.64 (q, J ) 7.6 Hz, 2H),
3.91-3.98 (m, 4H), 6.97-7.20 (m, 4H), 7.09-7.12 (m, 6H),
7.32-7.33 (m, 5H) ppm.
Acknowledgment. Financial support for this research was
provided by the National Science Council of Taiwan, ROC, and
National Taiwan University.
Supporting Information Available: Experimental proce-
dures and characterization data for compounds 4a, 6, and 9-14,
1H spectrum of 3 and 1H and 13C NMR spectra for new
compounds 9 and 12-14. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO900299Q
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