Simple modification in hexakis-addition for efficient synthesis of C 60-centered dendritic molecules bearing multiple aromatic chromophores

Article abstract of DOI:10.1021/ol0473851

(Chemical Equation Presented) In the templated hexakis-addition reaction of malonic esters with C₆₀ to prepare dendritic macromolecules that are terminated symmetrically with 12 derivatized pyrenes, a simple modification to use a much larger excess of the bromination agent resulted in dramatic increases in the product yields.

Full text of DOI:10.1021/ol0473851

ORGANIC
LETTERS
2005
Vol. 7, No. 5
859-861
Simple Modification in Hexakis-Addition
for Efficient Synthesis of C60-Centered
Dendritic Molecules Bearing Multiple
Aromatic Chromophores
Huaping Li, Alex Kitaygorodskiy, Rebecca A. Carino, and Ya-Ping Sun*
Department of Chemistry and Laboratory for Emerging Materials and Technology,
Clemson UniVersity, Clemson, South Carolina 29634-0973
syaping@clemson.edu
Received December 20, 2004
ABSTRACT
In the templated hexakis-addition reaction of malonic esters with C60 to prepare dendritic macromolecules that are terminated symmetrically
with 12 derivatized pyrenes, a simple modification to use a much larger excess of the bromination agent resulted in dramatic increases in the
product yields.
The highly symmetric molecule C60 is considered to be an
ideal core for dendritic molecular structures.1-3 In particular,
ever, the hexakis-addition of C60 with bulky and/or complex
functional groups typically suffers from low reaction yields,
often only a few percent on the basis of consumed C60.3,10-12
Because of the low yields, the separation of the desired
hexakis-adducts from reaction mixtures is by no means a
straightforward task. In our synthesis of the C60-centered
dendritic macromolecules bearing multiple aromatic chro-
mophores (1-3 in Scheme 1),13 we found a simple modi-
fication to the commonly used reaction conditions for the
templated hexakis-addition of C60 to achieve substantially
improved product yields.
C
60 can be functionalized in a highly symmetric fashion via
templated hexakis-addition reactions.4-9 Several C60-centered
dendritic macromolecules have been synthesized.3,10-12 How-
(1) Hirsch, A.; Vostrowsky, O. Top. Cur. Chem. 2001, 217, 51.
(2) Nierengarten, J. F. Top. Cur. Chem. 2003, 228, 87.
(3) Fu, K.; Kitaygorodskiy, A.; Sun, Y.-P. Chem. Mater. 2000, 12, 2073.
(4) Herzog, A.; Hirsch, A.; Vostrowsky, O. Eur. J. Org. Chem. 2000,
171.
(5) Schick, G.; Levitus, H.; Kvetko, L.; Johnson, B. A.; Lamparth, I.;
Lunkwitz, R.; Ma, B.; Khan, S. I.; Garcia-Garibay, M.; Rubin, Y. J. Am.
Chem. Soc. 1999, 121, 3246.
(6) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537.
(7) Lamparth, I.; Maichle-Mo¨ssmer, C.; Hirsch, A. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1607.
(8) Camps, X.; Hirsch, A. J. Chem. Soc., Perkin Trans. 1 1997, 1595.
(9) Cardullo, F.; Seiler, P.; Isaacs, L.; Nierengarten, J. F.; Haldimann,
R. F.; Diederich, F.; MordasiniDenti, T.; Thiel, W.; Boudon, C.; Gissel-
brecht, J. P.; Gross, M. HelV. Chem. Acta 1997, 80, 343.
(10) Camps, X.; Scho¨nberger, H.; Hirsch, A. Chem. Eur. J. 1997, 3,
561.
The malonic esters in Scheme 1 were prepared by using
procedures similar to those already reported in the literature.14
The experimental details are provided in Supporting Infor-
mation. The commonly used reaction conditions for the
(12) Chuard, T.; Deschenaux, R.; Hirsch, A.; Scho¨nberger, H. Chem.
Commun. 1999, 2103.
(13) Martin, R. B.; Fu, K.; Li, H. P.; Cole, D.; Sun, Y.-P. Chem. Commun.
2003, 2368.
(11) Camps, X.; Dietel, E.; Hirsch, A.; Pyo, S.; Echegoyen, L.; Hackbarth,
S.; Bo¨der, B. Chem. Eur. J. 1999, 5, 2362.
(14) Martin, R. B.; Fu, K.; Sun, Y.-P. Chem. Phys. Lett. 2003, 375, 619.
10.1021/ol0473851 CCC: $30.25
© 2005 American Chemical Society
Published on Web 02/08/2005

Scheme 1
templated hexakis-addition of C60 are generally the same as
mg, 0.5 mmol) and an excess amount of carbon tetrabromide
(1.62 g, 5 mmol, 10 times that commonly used in the
literature8,13). The resulting solution was stirred for 30 min,
followed by the addition of DBU (150 mg, 1 mmol). After
constant stirring at room temperature for 8 days, the reaction
mixture was filtered, concentrated, and separated on a silica
gel column by using first hexane and then chloroform as
eluents. The desired fraction in chloroform was concentrated
and precipitated into hexane, and the precipitate was filtered
and washed with acetone to obtain 1 as a yellow-colored
solid (20 mg, 10% yield). The molecular structure of 1 was
confirmed by results from both NMR and the matrix-assisted
laser desorption ionization-time-of-flight (MALDI-TOF)
MS characterizations.15 Apparently, the simple modification
of using a much larger excess of the bromination agent while
keeping other reaction parameters constant changed the
preparation of 1 from being impossible to producing a decent
yield.
those originally reported by Hirsch and co-workers.7,8 These
conditions were applied to the synthesis of compounds 1-3.
For compound 2,13 as an example, the reaction conditions
were to use o-dichlorobenzene as the solvent and to match
the amount of C60 (0.05 mmol) with the templating agent
9,10-dimethylanthracene at 10 equiv, the malonic ester at
10 equiv, carbon tetrabromide at 10 equiv, and the base 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) at 20 equiv. A prod-
uct yield of 17% could be achieved.13 However, the same
set of reaction conditions for the synthesis of 1 resulted in
only a negligible amount of product, insufficient for any
meaningful separation and isolation of the compound. On
the other hand, while the synthesis of compound 3 under
similar conditions was possible, with a comparable product
yield of 16%, the compound was in a complex reaction
mixture and thus very difficult to separate and especially
challenging to obtain in a purified form.
In a search for better yields in the synthesis of 1-3, we
found that a simple modification to the commonly used
conditions could substantially improve the hexakis-addition
reactions. With such a modification of using a much larger
excess of the bromination agent carbon tetrabromide, 5-10
times the usual amount, compound 1 could be synthesized
and isolated in 10% yield, and the yields for compounds 2
and 3 were more than doubled.
For the synthesis of 1 under the modified reaction
conditions, a solution of purified C60 (35 mg, 0.05 mmol)
and 9,10-dimethylanthracene (100 mg, 0.5 mmol) in o-
dichlorobenzene (50 mL) was prepared and stirred for 5 h.
To the solution was added bis(pyrenemethyl) malonate (266
Similarly, the large excess in carbon tetrabromide under
otherwise the same reaction conditions increased the yield
of compound 2 from 17 to 35%.16 For compound 3,17 there
was not only a more than doubling of the product yield to
40% but also a much improved separation and purification
of the sample via conventional silica gel column chroma-
tography. For the latter, we speculate that the modified
(15) 1H NMR (500 MHz, CDCl3) δ 7.95 (d, J ) 7.5 Hz, 12H), 7.86 (d,
J ) 7.5 Hz, 12H), 7.80 (s, 12H), 7.76∼7.65 (m, 48H), 7.57 (d, J ) 7.5 Hz,
12H), 7.42 (d, J ) 7.5 Hz, 12H), 5.57 (s, 24H) ppm; 13C NMR (125 MHz,
CDCl3) δ 163.18, 146.62 (cage sp2), 141.96 (cage sp2), 134.76, 134.27,
130.59, 129.39, 128.20, 127.93, 127.84, 127.53, 127.27, 126.01, 125.49,
125.42, 124.75, 124.24, 122.37, 120.09, 70.04 (cage sp3), 67.04, 46.48 ppm;
MALDI-TOF MS (M+) 3904.
860
Org. Lett., Vol. 7, No. 5, 2005

reaction conditions might be against the formation of
byproducts with similar molecular structures to that of the
hexakis-adduct (such as pentaadducts), which thus made it
easier to isolate the compound from the reaction mixture.
There are generally speaking a limited number of C60
hexakis-adducts available in the literature, with hardly any
C60-centered dendritic macromolecules symmetrically func-
tionalized with multiple chromophores for comparison. This
is probably a result of the difficulty associated with hexakis-
addition under the commonly used reaction conditions (which
do not allow the preparation of 1, for example). A summary
of other C60 hexakis-adducts with various functionalities,
based on an exhaustive literature search, is provided in
Supporting Information. Except for those of simple dialkyl
malonic esters,8,18-23 the hexakis-adducts are always produced
in low yields and are typically separated from their respective
reaction mixtures by using specialized HPLC techniques,
reflecting the level of technical challenge and complexity.
Thus, the simple modification reported here for substantially
higher yields in the templated hexakis-addition of bulky and/
or complex malonic esters may have broad implications in
the synthesis of C60-centered dendritic macromolecules with
currently unaccessible functionalities.
Acknowledgment. We thank S. Kumar, B. Zhou, and
R. B. Martin for experimental assistance. Financial support
from NSF and the Center for Advanced Engineering Fibers
and Films (NSF-ERC at Clemson University) is gratefully
acknowledged. R.C. was a participant of the Summer
Undergraduate Research Program sponsored jointly by NSF
and Clemson University.
Supporting Information Available: Experimental details
on the synthesis and characterization of the malonic esters
and a summary of other C60 hexakis-adducts with various
functionalities. This material is available free of charge via
the Internet at http://pubs.acs.org.
(16) Compound 2:13 1H NMR (500 MHz, CDCl3) δ 8.03∼8.02 (m, 2H),
7.97 (d, J ) 7.5 Hz, 12H), 7.89∼7.81 (m, 72H), 7.09 (d, J ) 8.5 Hz, 24H),
6.84 (d, J ) 8.5 Hz, 24H), 5.41 (s, 24H), 5.15 (s, 24H) ppm; 13C NMR
(125 MHz, CDCl3) δ 163.70, 159.10, 145.87 (cage sp2), 141.10 (cage sp2),
131.33, 131.05, 130.57, 130.50, 129.47, 129.04, 127.86, 127.39, 127.19,
127.13, 126.69, 125.79, 125.20, 124.68, 124.45, 122.82, 114.79, 69.15 (cage
sp3), 68.53, 68.36, 45.59 ppm; MALDI-TOF MS (M+) 5177.
(17) Purified C60 (35 mg, 0.05 mmol) and DMA (100 mg, 0.5 mmol)
were dissolved in o-DCB (50 mL). After the solution was stirred at room
temperature for 5 h, carbon tetrabromide (1.62 g, 5 mmol) and bis-
(pyrenebutyl) malonate (308 mg, 0.5 mmol) were added. The solution was
stirred for another 30 min, followed by the addition of DBU (150 mg, 1
mmol). After reaction for 8 days, the solvent o-DCB was removed. The
solid sample was separated on a silica gel column by using first hexane to
remove DMA and then chloroform to isolate the hexakis-adduct. The
chloroform fraction thus collected was concentrated and then precipitated
into hexane. The precipitate was filtered and washed with acetone to obtain
3 as a yellow-colored solid (88 mg, 40% yield): 1H NMR (500 MHz,
CDCl3) δ 7.98∼7.82 (m, 96H), 7.50 (d, J ) 7.5 Hz, 12H), 4.01 (t, J ) 6.5
Hz, 24H), 2.95 (t, J ) 7.5 Hz, 24H), 1.60∼1.50 (m, 48H) ppm; 13C NMR
(125 MHz, CDCl3) δ 166.37, 145.90 (cage sp2), 141.10 (cage sp2), 135.90,
131.43, 130.89, 129.88, 128.59, 127.46, 127.28, 127.12, 126.63, 125.80,
125.10, 124.88, 124.77, 124.70, 123.20, 69.40 (cage sp3), 66.70, 45.65,
32.86, 28.44, 27.87 ppm; MALDI-TOF MS (M+) 4409.
OL0473851
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