Dihydroazulene-buckminsterfullerene conjugates

Article abstract of DOI:10.1021/jo301306y

The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has recently attracted interest as a molecular switch for molecular electronics. In this field, Buckminsterfullerene, C₆₀, has been shown to be a useful anchoring group for adhering a molecular wire to an electrode. Here we have combined the two units with the overall aim to elucidate how C₆₀ influences the DHA-VHF switching events. Efficient synthetic protocols for making covalently linked DHA-C₆₀ conjugates were developed, using Prato, Sonogashira, Hay, and Cadiot-Chodkiewicz reactions. These syntheses provide as well a variety of potentially useful DHA and C₆₀ building blocks for acetylenic scaffolding. The two units were separated by bridges of various lengths, such as oligo(phenyleneethynylene) (OPE2 and OPE3) wires. The distance of separation was found to influence strongly the light-induced ring-opening reaction of DHA to its corresponding VHF. Thus, C₆₀ was found to significantly quench this conversion when situated closely to the DHA unit.

Full text of DOI:10.1021/jo301306y

Article
pubs.acs.org/joc
Dihydroazulene−Buckminsterfullerene Conjugates
Marco Santella,†,‡ Virginia Mazzanti,†,‡ Martyn Jevric,† Christian Richard Parker,†
Søren Lindbæk Broman,† Andrew D. Bond,§ and Mogens Brøndsted Nielsen*,†
†Department of Chemistry and Nano-Science Center, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø,
Denmark
‡Sino-Danish Centre for Education and Research (SDC), Niels Jensens Vej 2, DK-8000 Aarhus C, Denmark
§Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
S
* Supporting Information
ABSTRACT: The dihydroazulene (DHA)/vinylheptafulvene
(VHF) photo/thermoswitch has recently attracted interest as a
molecular switch for molecular electronics. In this field,
Buckminsterfullerene, C60, has been shown to be a useful
anchoring group for adhering a molecular wire to an electrode.
Here we have combined the two units with the overall aim to
elucidate how C60 influences the DHA−VHF switching events.
Efficient synthetic protocols for making covalently linked DHA-
C60 conjugates were developed, using Prato, Sonogashira, Hay, and
Cadiot−Chodkiewicz reactions. These syntheses provide as well a
variety of potentially useful DHA and C60 building blocks for
acetylenic scaffolding. The two units were separated by bridges of various lengths, such as oligo(phenyleneethynylene) (OPE2
and OPE3) wires. The distance of separation was found to influence strongly the light-induced ring-opening reaction of DHA to
its corresponding VHF. Thus, C60 was found to significantly quench this conversion when situated closely to the DHA unit.
iodoacetophenone, derivatives 16 and 27 with a phenyl or p-
iodophenyl at position 2 are readily prepared in few steps on a
large scale.
INTRODUCTION
■
Molecules that change their single-molecule conductivity upon
an external stimulus are interesting as components for
molecular electronics devices.1 Light is a particularly attractive
Much work in the field of molecular electronics has also
focused on the nontrivial contacting of the molecule to an
stimulus for triggering such conductivity changes, and several
electrode. In particular, thiolate end groups8 have been
molecular electronics studies have in recent years focused on
photoswitches such as dithienylethenes2 and azobenzenes.3
Recently it was shown that derivatives of dihydroazulene
employed as anchoring groups (“molecular alligator clips”) as
these groups adhere well to gold. Recently, however,
Buckminsterfullerene, C60, was successfully employed as an
(DHA) can also be employed for light-triggered conductance
switching in single-molecule devices.4 DHA undergoes a 10-
anchoring group, providing a well-defined contact region to
gold.9 Moreover, several synthetic protocols have been devised
electron retro-electrocyclization upon irradiation to furnish a
for preparing molecular wires with C60 end caps,10 typically
vinylheptafulvene (VHF), which can exist as s-cis and s-trans
employing a [3 + 2] dipolar cyclization (Prato reaction11) or an
acetylide addition reaction.10a Stimulated by the DHA−VHF
conductance switching and the beneficial molecular wiring via
C60 anchoring, we became interested to link these two entities
together. Here we present synthetic protocols for obtaining
such DHA-C60 conjugates in which the distance between the
DHA and C60 is varied in a systematic manner, using rigid and
π-conjugated linkers (Chart 1). Indeed, this distance was found
to influence strongly the light-induced ring-opening of the
DHA unit; at close distances, the light-induced ring-opening
reaction occurred less readily. Compounds 3a/b−5 were
prepared by a Prato reaction in the final step using DHA
precursors with an incorporated aldehyde functionality. In
conformers (Scheme 1).5 When VHF is in its s-cis
conformation, it can undergo a thermally induced ring closure
to regenerate DHA. Starting from either acetophenone or p-
Scheme 1
Received: June 22, 2012
Published: September 17, 2012
© 2012 American Chemical Society
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Chart 1
addition, we have devised a route to compound 4 via a final
Sonogashira cross-coupling12 reaction. Compound 6 was made
by an unsymmetrical Hay coupling13 from the corresponding
alkyne precursors as well as by a palladium-catalyzed version of
the Cadiot−Chodkiewicz cross-coupling14 from terminal alkyne
and bromoalkyne precursors. The central conjugated part
separating the DHA and C60 cores in compounds 4 and 5 is an
oligo(phenyleneethynylene), OPE2 and OPE3, respectively.
This is noteworthy in view of the fact that OPEs have been
explored considerably as molecular wires for molecular
electronics.8,15 The design of C60 conjugates usually has to
take into consideration the poor solubility of such compounds.
This can be addressed by the introduction of solubilizing
groups upon the nitrogen atom of the pyrrolidine ring using
tailor-made amino acids in the Prato reaction. The propylox-
ybenzyl substituent was chosen to provide solubility of the
products; hexyloxybenzyl has previously been used with success
for this purpose, and in addition, its use has shown short
reaction times with decent conversion.16 One conjugate (3b)
without this group was, however, also prepared and studied to
support the quenching effect exerted by C60.
Scheme 2
(HMDS) and AcOH (Knoevenagel conditions of Barnes et
al.18). Treatment with tropylium tetrafluoroborate
RESULTS AND DISCUSSION
+
−
■
(C7H7 BF4 ) in the presence of triethylamine as base gave a
Synthesis. Our first objective was to develop a synthetic
route for DHA-C60 conjugates based on a final Prato reaction
between an aldehyde, a glycine derivative, and C60. First, glycine
was functionalized with the propyloxybenzyl substituent. Thus,
the known 4-propyloxybenzaldehyde (717) was treated with
glycine ethylester hydrochloride, and the intermediate imine
was reduced with sodium borohydride to furnish compound 8
(Scheme 2). The ester functionality was then hydrolyzed, and
the glycine derivative 9 was isolated as a fluffy solid at pH 6.7.
Synthesis of the DHA-aldehyde precursor for conjugates 3a
and 3b is shown in Scheme 3. The acetophenone 10 was
subjected to a Knoevenagel condensation with malononitrile to
furnish the product 11, in the presence of hexamethyldisilazane
mixture of products 12a/b. Subjecting this mixture to tritylium
tetrafluoroborate (Ph3C+BF4 ) followed by triethylamine
−
generated an intermediate VHF that was thermally converted
to DHA 13.19 Reduction of the ester group by the action of
DIBAL-H finally generated the aldehyde 14, which was,
however, difficult to obtain analytically pure due to instability
(required repeated column chromatography). The low yield
also reflects the fact that side reactions were clearly evident
during the progress of the reaction. Subjecting the compound
to Prato reactions using either 9 or N-ethylglycine furnished
DHA-C60 conjugates 3a and 3b (Scheme 3).
Next, conjugates 4 and 5 were targeted. The known iodo-
DHA 27 was subjected to Sonogashira cross-couplings with the
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Scheme 3
Scheme 4
exhibited an AB system of the benzyl CH2 protons around δ 4.5
and 3.7 ppm (J = 13.2 Hz). Although two chiral centers are
present in all of these products (position C-8a in DHA and the
methylene carbon in pyrrolidine), doubling of the signals due
to diastereoisomerism was noticed only when the two centers
were closer in proximity (compounds 3a and 3b).
The next objective was to employ Sonogashira or Hay
reactions to link the units together by acetylenic scaffolding.
Only few reports on metal-catalyzed coupling reactions on
suitable C60 derivatives are known in the literature.20 For this
purpose, C60 derivatives with iodophenyl or alkyne functional
groups were targeted. Thus, a Prato reaction between either 4-
iodobenzaldehyde (19) or 4-ethynylbenzaldehyde (20) and 9
and C60 provided the important building blocks 21 and 22
(Scheme 5). Gratifyingly, the iodide 21 underwent a
Sonogashira cross-coupling with trimethylsilylacetylene to
furnish compound 23. A DHA incorporating an ethynyl
group was therefore targeted as the next coupling partner.
This functionalization can be accomplished employing two
routes. In the route presented in Scheme 6, the iodo-DHA 2
was treated with triisopropylsilylacetylene under Sonogashira
conditions to provide compound 24. Desilylation was
accomplished using tetrabutylammonium fluoride, furnishing
the terminal alkyne product 25 in a yield of 76%. The reaction
had to be carried out under acidic conditions (to avoid azulene
formation21) and was rather slow as it required reflux for 16 h
in order to reach completion. In an alternative attempt, we
converted the DHA into VHF using aluminum chloride
(according to a procedure reported recently22) and then
subjected this compound to the fluoride source in the absence
of acid as VHF is not base-sensitive. However, after 24 h during
which the mixture was irradiated, TLC indicated no formation
of the terminal alkyne. As the trimethylsilyl group is easier to
cleave, we also prepared the corresponding trimethylsilylethyn-
yl-DHA, but the purification of this compound was tedious, and
we could not separate it from a byproduct formed under the
reaction conditions. Instead, an alternative route was developed
(Scheme 7), in which the alkyne functionality was incorporated
early in the synthesis before the DHA core is constructed.
Following analogous procedures for making 1 and 2,6,7 the
ketone 2623 was first subjected to a Knoevenagel condensation
with malononitrile to give compound 27. This compound was
known alkynes 15 and 16,10g respectively, to provide the DHA-
aldehydes 17 and 18 (Scheme 4). Single crystals of 17 were
grown from chloroform and subjected to X-ray crystallographic
analysis, confirming the structure (Figure S1, Supporting
Information). Finally, a Prato reaction between C60, the glycine
derivative 9, and each of the DHA-aldehydes 17 and 18
provided the DHA-C60 conjugates 4 and 5 (Scheme 4).
All DHA-C60 conjugates exhibited good solubility in organic
solvents and were isolated by column chromatography while
shielding the column from light to avoid conversions to VHFs.
They all contained two stereocenters (position 8a in DHA and
position 2 in pyrrolidine) and were isolated as mixtures of
diastereoisomers. The functionalization of the fullerene in each
conjugate product was supported by spectroscopy. For
1
example, H NMR of these fullerene-DHA hybrids gave rise
to the observance of characteristic pattern for a 2-substituted
fulleropyrrolidine in addition to being superimposed onto/
accompanying a typical DHA spectrum. This consisted of a
single resonance for the pyrrolidine CH proton at δ 5.2 ppm
and two doublets for the inequivalent methylene protons
around δ 4.9 and 4.2 ppm (J = 9.4 Hz). In addition, all fullerene
derivatives bearing the propyloxybenzyl solubilizing group also
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Scheme 5
Scheme 7
Scheme 6
upon treatment with tetrabutylammonium fluoride under acidic
conditions within 16 h at room temperature to provide the
terminal alkyne 25 in a yield of 53%. The yield of desilylation
could, however, be improved by another method. Thus,
treatment with silver nitrate in methanol generated the silver-
acetylide intermediate 30 that could be isolated as a yellow
solid (CAUTION: silver-acetylides are potentially explosive).
Subsequent treatment with a saturated aqueous solution of
potassium iodide then provided 25 in an overall yield of 86%
from 29. With the new building blocks at hand, metal-catalyzed
coupling reactions were attempted. Indeed, the iodide 21 and
the alkyne 25 were successfully coupled together under
Sonogashira conditions affording the conjugate 4 (Scheme 8).
Moreover, the two terminal alkynes 22 and 25 were coupled
together under oxidative Hay conditions (using chlorobenzene
as solvent20e) (Scheme 9) to furnish the butadiyne-bridged
conjugate 6 (together with homocoupled byproduct of each
starting material; the homocoupling products are not a point of
discussion here as this is the subject of a separate investigation).
This compound can also be prepared by a palladium-catalyzed
version of the Cadiot−Chodkiewicz cross-coupling (Scheme
9). First, the bromoalkyne 31 (of limited stability) was
+
−
then treated with tropylium tetrafluoroborate (C7H7 BF4 ) in
the presence of triethylamine as base to furnish the product 28.
Hydride abstraction by the action of tritylium tetrafluoroborate
(Ph3C+BF4 ) followed by proton abstraction by triethylamine
generated the intermediate VHF that was thermally converted
to the DHA product 29. Desilylation could now be completed
−
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Scheme 8
Figure 1. 2:1 Complex between DHA 2 and C60 (with displacement
ellipsoids at 50% probability for non-H atoms). CCDC 886632.
trigonal space. The other cyano group points across the face of
one C60 molecule, forming a contact of ca. 3.19 Å between the
terminal N atom and the centroid of one benzene ring. The
plane of the iodophenyl ring forms a π−π interaction with
another C60 molecule, with an interplanar separation of ca. 3.15
Å. The I atom points toward a third C60 molecule, with a
shortest I···C contact of ca. 3.45 Å.
Scheme 9
Spectroscopy and Switching Studies. All five DHA-C60
complexes 3a, 3b, 4, 5, and 6 as well as the two OPE aldehydes
17 and 18 could be converted to their corresponding VHFs
upon irradiation. The absorption maxima are listed in Table 1,
and the absorption spectra of DHA 3a and its corresponding
VHF are shown in Figure 2 as representative examples. It
should be noted that the characteristic DHA absorption, usually
found around 350 nm,6 is overlapping with the absorption of
the C60 moiety. The fullerene substituent was found to have
little influence on the thermally induced ring closure of VHF to
DHA as revealed by the rate constants and half-lives at 50 °C
listed in Table 1. The OPE bridges exert themselves a rate-
enhancing effect (as expected for an electron-withdrawing
group at this position21,24), while the presence of C60 causes
only small changes. Thus, VHFs corresponding to DHAs 4 and
17 behave rather similarly as do VHFs corresponding to DHAs
5 and 18.
The photoresponses of the DHAs were studied in 1,2-
dichloroethane at the same wavelength of irradiation (351 nm).
A 1:1 sample of DHA 1 and C60-derivative 22 was also
investigated. Irradiation of each sample (ca. 10−5 M) was
performed at intervals for at least 10 min in total, and the
absorbance maximum of the corresponding VHF species was
plotted against the time of irradiation. By curve fitting, the time
at which half of the DHA had been converted into VHF was
determined. After correcting for different concentrations and
differences in sample absorbances (for details, see Supporting
Information), we obtain the following estimated ratios of
“quantum yields” for the ring-opening reaction, ϕ (com-
pound)/ϕ (1) = 0.03 (3b), 0.04 (3a), 0.2 (4), 0.3 (6), 0.7 (5),
1.0 (1 + C60, 1:1) (Figure 3). When performing the light-
induced ring-opening on 3a and 5 at about 10 times more
dilute concentrations, we obtain a similar ratio in quantum
yields of ring-opening for the two species as that obtained at the
higher concentration (ϕ (5)/ϕ (3a) ∼17−19 from the two
experiments). The ratios in quantum yields listed above present
some rough estimates, but the data show a clear trend: the
closer C60 is placed to the DHA, the lower the ratio of quantum
yields. In other words, a covalently attached C60 exerts a
quenching influence on the ring-opening, which is possibly
explained by light-induced electron transfer to this acceptor
unit (although we cannot exclude other quenching mecha-
prepared in high yield by treating the DHA 25 with N-
bromosuccinimide (NBS) and AgNO3. Next, treating it with
the alkyne 22 and the Pd(PPh3)4/CuI catalyst system at room
temperature did not provide any of the product 6 according to
TLC inspection; only products corresponding to homocou-
pling of 22 (in a trace amount) and debromination of 31 were
observed. However, subjecting the reaction mixture to
microwave heating (70 °C) resulted in formation of the
product 6, which was isolated in a yield of 38% after column
chromatographic purification (the product of homocoupling of
22 was also isolated as a byproduct). The yield from the
Cadiot−Chodkiewicz reaction is thus slightly higher than that
obtained from the Hay reaction, but on the other hand, it
includes one additional step, namely, synthesis of the
bromoalkyne precursor.
The structures described above have the DHA and C60 units
covalently linked together. It is also interesting to elucidate how
the units would interact by noncovalent interactions. We
managed to grow crystals of the iodo-DHA 2 and C60 from
CS2/CH2Cl2. X-ray crystallographic analysis revealed a 2:1
complex in the solid state (Figure 1). In the structure, the iodo-
DHA molecules are sandwiched between hexagonal close-
packed (hcp) layers of C60 molecules. Each iodo-DHA
molecule lies above a hollow in the hcp C60 layer, with one
of its cyano groups pointing directly into the center of the
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Table 1. Absorption Maxima of DHAs and VHFs (25 °C) and Measured Rate Constants for Thermally Induced Back Reaction
a
(VHF → DHA) at 50 °C
λDHA [nm]
352
ε [Lmol−1 cm−1
]
λVHF [nm]
ε [Lmol−1 cm−1
]
k50 °C [s−1
]
t1/2, 50 °C [min]
1
475
478
476
480
480
481
482
480
3a
3b
4
329/362 (sh)
329/357 (sh)
313/372 (sh)
381
30/25 × 103
45/40 × 103
56/45 × 103
40 × 103
15 × 103
10 × 103
25 × 103
19 × 103
14 × 103
28 × 103
18 × 103
30.3 × 10−5
37.4 × 10−5
70.6 × 10−5
71.0 × 10−5
81.1 × 10−5
61.9 × 10−5
73.2 × 10−5
38.1
30.9
16.4
16.3
14.2
18.7
15.8
5
6
381
29 × 103
17
18
384
38 × 103
386
36 × 103
a
Solvent: 1,2-dichloroethane; sh = shoulder.
CONCLUSION
■
In conclusion, we have developed efficient synthetic protocols
for linking together the dihydroazulene photoswitch to
Buckminsterfullerene via conjugated phenyleneethynylene
bridges. In one procedure, the products are obtained by a
final Prato reaction. Useful dihydroazulene and C60 building
blocks for acetylenic scaffolding were developed and were
successfully coupled together by Sonogashira, Hay, and
Cadiot−Chodkiewicz reactions, providing convenient alter-
native ways of obtaining DHA-C60 conjugates. These coupling
reactions have previously been used only scarcely on C60
derivatives, but as shown here they are indeed viable methods
to pursue further in the future. The light-induced ring-opening
reaction was found to depend strongly on the distance between
the two units. Thus, the C60 end group was observed to quench
the ring-opening reaction. These results are important for the
further exploration of the conjugates in light-controlled
molecular electronics devices when using C60 as an anchoring
group. Our recently developed synthesis protocols21,24 for
functionalizing the DHA core at the seven-membered ring may
allow incorporation of fullerene anchoring groups at both poles
of the molecule via linkers of suitable lengths. It would be
particularly interesting to investigate the conductivity of such
dumbbell-like molecules in single-molecule junctions and, in
particular, the possibility for light-induced conductance switch-
ing.
Figure 2. Absorption spectra of DHA 3a and its corresponding VHF
in 1,2-dichloroethane.
Figure 3. Structures of DHA-C60 conjugates and estimated quantum
yields (ϕ) for the DHA → VHF conversion relative to that of DHA 1,
i.e., quantum yield ratios.
EXPERIMENTAL SECTION
■
General Methods. Chemicals were used as purchased from
commercial sources. THF was distilled from sodium/benzophenone
couple. Compounds 2,7 7,17 16,10g and 2623 were synthesized
according to the respective literature procedures. Purification of
products was carried out either by flash chromatography on silica gel
(40−63 μm) or by dry column vacuum chromatography (DCVC)26
(15−40 μm). Thin-layer chromatography (TLC) was carried out using
nisms). It is important to note that 3b (devoid of a
propyloxyphenol unit) undergoes the light-induced ring-
opening reaction least readily, which signals that although the
propyloxyphenol substituent may also play a role, the large
effect originates from C60. The strong dependence on the
separation between DHA and C60 seems to indicate that the
quenching is of intramolecular origin. Nevertheless, the
formation of a complex between DHA 2 and C60 in the solid
state prompted us to investigate the possibility of quenching by
simply adding the C60 derivative 22 to a solution of DHA 1.
However, addition of 1 equiv of 22 had no influence,
supporting that any weak association between the two units
in solution cannot account for the quenching observed in the
conjugates. The quenching influence of an electron acceptor is
in accordance with our previous studies on a DHA-TTF
conjugate (TTF = tetrathiafulvalene).25 Oxidation of the TTF
unit to its corresponding radical cation (turning it into an
acceptor unit) thus had a retarding influence on the ring-
opening reaction.
1
aluminum sheets precoated with silica gel. H NMR (500 MHz) and
13C NMR (125 MHz) spectra were recorded on an instrument with
cryoprobe using the residual solvent as the internal standard (CDCl3,
1H 7.26 ppm and 13C 77.16 ppm; CD3OD, H 4.87 ppm and 13C
1
49.00 ppm.) All chemical shifts are quoted on the δ scale (ppm), and
all coupling constants (J) are expressed in Hz. In APT spectra
(Supporting Information), CH and CH3 correspond to negative
signals and C and CH2 correspond to positive signals. Matrix assisted
laser desorption ionization (MALDI) mass spectra were recorded on a
time-of-flight apparatus; all measurements were performed in negative
ion mode with trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-
propenylidene]malononitrile (DCTB) as matrix. Neat IR spectra
were acquired using an ‘ATR platinum Diamond 1 Refl’ accessory or
as films upon a silicon window. Melting points are uncorrected. UV−
vis spectroscopic measurements were performed in a 1-cm path length
quartz cuvette.
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Ethyl-2-(4-propyloxybenzylamino)acetate (8). To a solution
of 4-propyloxybenzaldehyde 7 (6.20 g, 37.8 mmol), glycine ethylester
hydrochloride (5.05 g, 36.3 mmol), and NEt3 (5.8 mL, 40 mmol) in
the presence of starting material adjudged by TLC, the mixture was
again cooled to −78 °C where additional tropylium tetrafluoroborate
(1.28 g, 7.19 mmol) and NEt3 (1.00 mL, 7.19 mmol) were added. The
mixture was stirred for a further 4 h. The reaction mixture was poured
into brine, the organic phase was separated and dried over MgSO4 and
filtered, and the solvents were removed in vacuo, yielding a yellow oil
consisting of a mixture of 12a and 12b and a small amount of
cycloheptatriene according to crude NMR. An aliquot of the mixture
was purified by dry column vacuum chromatography (SiO2, 12.6 cm2,
0−40% EtOAc/heptanes, 4% steps, 40 mL fractions), and compound
12a was isolated as a colorless oil. Due to the instability, the remains of
the reaction mixture were used directly in the next step. Compound
12a: Rf = 0.37 (3:7 EtOAc/heptanes). IR (neat) νmax (cm−1): 3019s,
2953s, 2847m, 2253m, 2231s, 1717vs, 1662m, 1609m, 1583m, 1561
m. 1H NMR (500 MHz, CDCl3): δ 8.13 (d, J = 8.6 Hz, 1H), 7.45 (d, J
= 8.6 Hz, 1H), 6.65 − 6.54 (m, 1H), 6.25 − 6.15 (m, 1H), 5.14 (dd, J
= 9.1, 6.4 Hz, 1H), 3.94 (s, 2H), 3.19 (d, J = 8.0 Hz, 1H), 2.02−1.88
(m, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ 177.2, 165.9, 138.9,
133.1, 131.3, 130.4, 127.5, 126.7, 122.7, 112.1, 87.9, 52.7, 39.0, 37.6
ppm. ES-MS: m/z 339 ([M + Na]+). The oil was dissolved in 1,2-
dichloroethane (250 mL). Tritylium tetrafluoroborate (5.84 g, 17.7
mmol) was added, and the resulting dark red solution was stirred for 2
h at 80 °C. The reaction mixture was cooled to 0 °C, after which NEt3
(2.46 mL, 17.7 mmol) was added in portions over 1 h, and the mixture
was allowed to heat to rt. The black reaction mixture was then heated
to 80 °C for 1 h. After cooling, the solvents were removed in vacuo.
Purification by flash column chromatography (SiO2, 33% EtOAc/
heptanes) followed by recrystallization from CCl4 gave 13 (1.25 g,
22%) as a dark yellow crystalline solid. Mp 153.6−155.0 °C, lit.19 152
°C. Rf = 0.52 (1:1 EtOAc/heptanes). IR (neat) νmax (cm−1): 3022w,
́
dry CH2Cl2 (50 mL) was added 3 Å molecular sieves. The mixture was
allowed to stir at rt for 16 h. The resulting mixture was filtered, and the
solvent was removed under reduced pressure to give the imine as a
white solid. The solid was then dissolved in MeOH (50 mL), and the
mixture was cooled by an ice bath. Sodium borohydride (1.55 g, 40.8
mmol) was carefully added portion-wise to the stirring solution. After
10 min, saturated aqueous sodium bicarbonate (100 mL) was added,
and the reaction mixture was extracted with CH2Cl2 (3 × 100 mL).
The combined organic phases were dried over Na2SO4 and filtered,
and the solvent was removed to give a crude oil, which was
subsequently purified by column chromatography (SiO2, 3:2 EtOAc/
heptane) to give the title compound as a colorless oil (6.52 g, 69%). Rf
= 0.34 (3:2 EtOAc/heptane). IR (ATR) νmax (cm−1): 3341w, 3063w,
3032w, 2956m, 2937m, 2876m, 1736vs, 1652m, 1611s, 1583m,
1510vs, 1465s, 1420m, 1392s, 1376sh. 1H NMR (500 MHz, CDCl3): δ
7.24−7.21 (m, 2H), 6.86−6.84 (m, 2H), 4.18 (q, J = 7.1 Hz, 2H), 3.90
(t, J = 6.6 Hz, 2H), 3.73 (s, 2H), 3.38 (s, 2H), 1.87 (broad s, 1H),
1.83−1.76 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H), 1.03 (t, J = 7.4 Hz, 3H).
13C NMR (125 MHz, CDCl3): δ 172.6, 158.5, 131.5, 129.6, 114.6,
69.6, 60.8, 52.8, 50.1, 22.7, 14.4, 10.6. ES-MS: m/z 274 ([M + Na]+),
252 ([M + H]+). Anal. Calcd for C14H21NO3: C 66.91, H 8.42, N 5.57.
Found: C 67.08, H 8.49, N 5.47.
2-(4-Propyloxybenzylamino)acetic Acid (9). To a solution of 8
(5.47 g, 21.8 mmol) in 50% aqueous MeOH (100 mL) was added
NaOH (1.42 g, 35.5 mmol), and the mixture was stirred until TLC
indicated complete consumption of the starting material. The MeOH
was removed by rotary evaporation, and the solution was diluted
further with water (100 mL). The solution was acidified with aqueous
1 M HCl until pH 6.7 was achieved. The white precipitate was filtered
and washed with water several times to afford the title amino acid as
white solid (3.46 g, 71%). The amino acid was dried under high
vacuum for 24 h prior to use in subsequent Prato reactions. Mp
197.5−198.5 °C. IR (ATR) νmax (cm−1): 3011m, 2967m, 2937m,
2917m, 2873m, 2790m, 2697m, 3200−2700brm, 2700−2000brm,
1
2952w, 2249w, 1722s, 1606m, 1586w, 1559w. H NMR (500 MHz,
CDCl3): δ 8.14−8.12 (m, 2H), 7.82−7.79 (m, 2H), 7.00 (s, 1H), 6.60
(dd, J = 11.2, 6.3 Hz, 1H), 6.52 (dd, J = 11.2, 6.1 Hz, 1H), 6.41 (broad
d, J = 6.3 Hz, 1H), 6.32 (ddd, J = 10.2, 6.1, 2.1 Hz, 1H), 5.83 (dd, J =
10.2, 3.8 Hz, 1H), 3.95 (s, 3H), 3.84 (ddd, J = 3.8, 2.1, 2.1 Hz, 1H)
ppm. 13C NMR (125 MHz, CDCl3): δ 166.3, 139.1, 138.4, 134.7,
134.5, 131.7, 131.2, 131.0, 130.6, 127.9, 126.3, 122.4, 119.7, 115.0,
112.6, 52.5, 51.2, 45.2 ppm. ES-MS: m/z 337 ([M + Na]+).
1
1908brw, 1597vs, 1514s, 1463s, 1451s, 1430s, 1395vs. H NMR (500
2-(4-Formylphenyl)-1,8a-dihydroazulene-1,1-dicarbonitrile
(14). A solution of DIBAL-H (3.0 mL, 1M in heptane, 3.0 mmol) was
added in portions over 6 h to a stirred solution of the ester 13 (296
mg, 0.94 mmol) in dry toluene (50 mL) at −89 °C. The reaction was
quenched with aqueous 0.1 M HCl (50 mL), and extracted with Et2O
(2 × 50 mL). The combined organic phases were washed with
aqueous NH4Cl (3 × 50 mL) and concentrated in vacuo. Purification
by flash column chromatography (SiO2, 10% THF/heptane) gave the
aldehyde 14 as a yellow solid (23 mg, 9%). Mp 151−152 °C. Rf = 0.44
(1:1 EtOAc/heptanes). IR (neat) νmax (cm−1): 2956w, 2925w, 2853w,
2200w, 1700s, 1603m, 1581w, 1560w. 1H NMR (500 MHz, CDCl3): δ
10.06 (s, 1H), 8.00−7.97 (m, 2H), 7.91−7.89 (m, 2H), 7.04 (s, 1H),
6.60 (dd, J = 11.2, 6.2 Hz, 1H), 6.54 (dd, J = 11.2, 6.1 Hz, 1H), 6.44
(broad d, J = 6.1 Hz, 1H), 6.34 (ddd, J = 10.2, 6.2, 2.1 Hz, 1H), 5.85
(dd, J = 10.3, 3.9 Hz, 1H), 3.83 (ddd, J = 3.9, 2.1, 2.1 Hz, 1H). 13C
NMR (125 MHz, CDCl3): δ 191.2, 138.7, 138.2, 136.8, 136.0, 135.2,
132.0, 130.9, 130.6, 128.0, 126.8, 122.9, 119.7, 114.9, 112.5, 51.2, 45.2.
ES-MS: m/z 307 ([M + Na]+), 285 ([M + H]+).
DHA-C60 Conjugate (3a). A degassed mixture of C60 (151 mg,
0.210 mmol), compound 14 (31 mg, 0.109 mmol), and 2-(4-
propoxybenzylamino)acetic acid (9) (128 mg, 0.549 mmol) in toluene
(100 mL) was refluxed for 12 h. The solvent was removed under
reduced pressure, and the crude residue was subjected to column
chromatography (SiO2, gradient elution from CS2 to 3:7 toluene/CS2)
to afford the title compound as a dark brown solid (22 mg, 17%). Rf =
0.35 (3:7 toluene/CS2). IR (ATR) νmax (cm−1): 3017vw, 2955w,
2914w, 2887w, 2785w, 1607m, 1580w, 1507s, 1461m, 1418m, 1374w,
1356w, 1298w, 1237s. 1H NMR (500 MHz, CDCl3): δ 8.05 (broad s,
2H), 7.83 (broad d, J = 7.8 Hz, 2H), 7.57−7.53 (m, 2H), 7.04−7.01
(m, 2H), 6.92 and 6.91 (2s, 1H), 6.58−6.54 (m, 1H), 6.49−6.45 (m,
1H), 6.33 (broad d, J = 6.0 Hz, 1H), 6.31−6.28 (m, 1H), 5.82−5.79
(m, 1H), 5.22 (s, 1H), 4.86 (d, J = 9.5 Hz, 1H), 4.49 and 4.48 (2d, J =
MHz, CD3OD): δ 7.39−7.36 (m, 2H), 6.98−6.95 (m, 2H), 4.11 (s,
2H), 3.95 (t, J = 6.6 Hz, 2H), 3.44 (s, 2H), 1.83−1.76 (m, 2H), 1.04
(t, J = 7.4 Hz, 3H). The amine NH and acid CO2H protons were not
visible due to exchange. 13C NMR (125 MHz, CD3OD): δ 170.8,
161.5, 132.4, 124.6, 116.0, 70.7, 51.5, 23.6, 10.8. ES-MS: m/z 246 ([M
+ Na]+), 224 ([M + H]+). Anal. Calcd for C12H17NO3: C 64.55, H
7.67, N 6.27. Found: C 64.76, H 7.67, N 6.18.
Methyl 4-(1,1-Dicyanoprop-1-en-2-yl)benzoate (11). HMDS
(7.1 mL, 5.4 g, 34 mmol) was carefully added to AcOH (18.8 mL, 19.7
g, 328 mmol). Upon completion, a solution of malononitrile (3.71 g,
56.1 mmol) and 10 (5.00 g, 28.1 mmol) in AcOH (9.3 mL, 9.7 g, 162
mmol) was added, and the resulting reaction mixture was stirred for 48
h at 75 °C. The solution was poured into water (300 mL) and
extracted with Et2O (3 × 100 mL). The combined extracts were
washed with water (2 × 100 mL) and brine (100 mL), dried over
MgSO4, and filtered, and the solvents were evaporated under reduced
pressure. The residue was triturated from EtOAc/heptanes to yield the
product as a yellow solid (5.97 g, 94%). Mp 95.2−96.6 °C Rf = 0.27
(3:7 EtOAc/heptanes). IR (ATR) νmax (cm−1): 3105vw, 3000vw,
2851w, 2226m, 1717s, 1608w, 1584m, 1557m, 1500w, 1434m, 1405m,
1
1381m, 1308m, 1279vs, 1183s. H NMR (500 MHz, CDCl3): δ 8.16
(d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 3.96 (s, 3H), 2.66 (s,
3H) ppm. 13C NMR (125 MHz, CDCl3): δ 174.4, 165.9, 140.0, 133.4,
130.4, 127.5, 112.4, 86.4, 52.7, 24.4 ppm. Anal. Calcd for C13H10N2O2:
C 69.00, H 4.46, N 12.39. Found: C 68.92, H 4.24, N 12.46. ES-MS:
m/z 249 ([M + Na]+), 227 ([M + H]+).
Methyl 4-(1,1-Dicyano-1,8a-dihydroazulen-2-yl)benzoate
(13). To a solution of 11 (4.00 g, 17.7 mmol) in CH2Cl2 (250 mL)
was added tropylium tetrafluoroborate (3.15 g, 17.7 mmol), and the
vessel was cooled to −78 °C. NEt3 (2.7 mL, 19.4 mmol) was added in
portions of 0.1 mL over 10 min. The reaction mixture was stirred
overnight during which the contents were allowed to reach rt. Due to
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13.2 Hz, 1H), 4.18 (d, J = 9.5 Hz, 1H), 4.00 and 3.99 (2d, J = 6.6 Hz,
2H), 3.79−3.76 (m, 1H), 3.67 (d, J = 13.2 Hz, 1H), 1.89−1.82 (m,
2H), 1.07 and 1.08 (2t, J = 7.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 158.9, 156.4, 156.4, 154.1, 153.2, 153.0, 153.0, 147.5, 146.7,
146.5, 146.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.1, 146.1, 146.1,
146.1, 145.9, 145.7, 145.7, 145.6, 145.6, 145.5, 145.5, 145.5, 145.5,
145.4, 145.34, 145.3, 144.9, 144.8, 144.8, 144.6, 144.5, 143.3, 143.1,
142.8, 142.7, 142.7, 142.7, 142.5, 142.4, 142.3, 142.3, 142.3, 142.3,
142.2, 142.1, 142.0, 141.8, 141.8, 141.7, 140.3, 140.3, 140.2, 140.1,
139.8, 139.8, 139.7, 139.6, 139.6, 138.7, 138.6, 137.2, 137.1, 136.6,
136.2, 135.8, 133.0, 133.0, 132.9, 131.1, 131.1, 131.0, 130.9, 130.3,
129.2, 129.2, 127.8, 127.8, 126.7, 126.7, 121.3, 121.3, 119.7, 119.5,
115.3, 115.2, 114.8, 112.8, 112.8, 80.9, 80.8, 80.8, 76.7, 69.7, 68.8, 68.8,
66.7, 56.3, 51.3, 51.3, 45.3, 45.3, 22.8, 10.8. MALDI-TOF-MS: m/z
1165 (M−). Anal. Calcd for C90H27N3O: C 92.69, H 2.33, N 3.60.
Found: C 92.54, H 2.30, N 3.58.
DHA-C60 Conjugate (3b). A degassed mixture of C60 (108 mg,
0.150 mmol), compound 14 (27 mg, 0.095 mmol), and N-ethylglycine
(105 mg, 1.02 mmol) in toluene (70 mL) was refluxed for 16 h. The
resulting brown solution was allowed to cool, and the solvent was
removed in vacuo. The crude residue was purified by column
chromatography (SiO2, gradient elution from CS2 to 1:4 toluene/CS2)
to give pure the title compound as a flaky brown solid (37 mg, 37%).
Rf = 0.40 (2:3 toluene/CS2). IR (neat) νmax (cm−1): 3029w, 2970s,
2933s, 2250w, 1540m, 1509w, 1186s .1H NMR (500 MHz, CDCl3): δ
7.93 (broad s, 2H), 7.79 (broad d, J = 8.1 Hz, 2H), 6.90 (s, 1H), 6.58−
6.54 (m, 1H), 6.49−6.45 (m, 1H), 6.33−6.28 (m, 2H), 5.82−5.79 (m,
1H), 5.14−5.12 (m, 2H), 4.18 (d, J = 9.4 Hz, 1H), 3.79−3.76 (m,
1H), 3.36−3.29 (m, 1H), 2.69−2.62 (m, 1H), 1.56 − 1.49 (m, 3H).
13C NMR (125 MHz, CDCl3): δ 156.5, 156.5, 154.3, 153.3, 153.1,
153.0, 147.5, 147.5, 146.7, 146.6, 146.5, 146.4, 146.4, 146.3, 146.3,
146.3, 146.1, 146.1, 145. 9, 145.7, 145.7, 145.6, 145.5, 145.5, 145.4,
145.4, 145.3, 144.9, 144.8, 144.6, 143.3, 143.1, 142.9, 142.7, 142.7,
142.7, 142.5, 142.4, 142.3, 142.3, 142.3, 142.2, 142.1, 142.1, 142.0,
141.8, 141.7, 141.7, 140.4, 140.3, 140.2, 140.1, 139.9, 139.8, 139.8,
138.8, 138.7, 137.2, 137.2, 136.7, 136.1, 135.8, 132.9, 132.8, 131.1,
131.1, 131.0, 130.7, 130.4, 130.4, 130.4, 127.8, 127.8, 126.6, 121.2,
121.2, 119.6, 119.5, 115.3, 115.2, 112.8, 112.8, 81.9, 81.9, 76.7, 69.1,
66.6, 51.3, 51.3, 47.4, 13.5. Anal. Calcd for C82H19N3: C 94.15, H 1.83,
N 4.02. Found: C 94.02, H 1.77, N 3.98.
2-{4-[2-(4-Formylphenyl)ethynyl]phenyl}-1,8a-dihydroazu-
lene-1,1-dicarbonitrile (17). To a degassed stirring solution of
compound 2 (352 mg, 0.92 mmol) and 4-ethynylbenzaldehyde (15)
(175 mg, 1.35 mmol) in a solvent mixture of THF (20 mL) and
diisopropylamine (20 mL) were added sequentially CuI (21 mg, 0.11
mmol) and Pd(PPh3)4 (75 mg, 0.065 mmol). The mixture was stirred
in the dark for 1 h. The solvent was removed in vacuo, and the crude
material was purified by flash column chromatography (SiO2, gradient
elution from toluene to 1:19 EtOAc/toluene) and chromatographed a
second time (SiO2, CH2Cl2) to afford the title compound as a bright
yellow solid (265 mg, 75%). Mp 185−187 °C (decomp). Rf = 0.34
(3:7 THF/heptane). IR (ATR) νmax (cm−1): 3028w, 2834w, 2737w,
2244vw, 2211w, 2151vw, 1686s, 1594s, 1558m, 1515m, 1436w,
1411m, 1388m, 1363w. 1H NMR (500 MHz, CDCl3): δ 10.04 (s, 1H),
7.90−7.88 (m, 2H), 7.76−7.74 (m, 2H), 7.71−7.69 (m, 2H), 7.65−
7.63 (m, 2H), 6.94 (s, 1H), 6.59 (dd, J = 11.4, 5.9 Hz, 1H), 6.50 (dd, J
= 11.4, 6.1 Hz, 1H). 6.39 (broad d, J = 5.9 Hz, 1H), 6.33 (ddd, J =
10.2, 6.1, 2.1 Hz, 1H), 5.83 (dd, J = 10.2, 3.8 Hz, 1H), 3.81 (ddd, J =
3.8, 2.1, 2.1 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 191.5, 139.3,
138.6, 135.8, 133.4, 132.7, 132.4, 131.5, 131.0, 130.8, 129.8, 129.2,
127.9, 126.3, 124.3, 121.8, 119.6, 115.1, 112.7, 92.7, 91.2, 51.3
(doublet signal due to incomplete decoupling), 45.17. MALDI-TOF-
MS: m/z 384 (M−). Anal. Calcd for C27H16N2O: C 84.36, H 4.20, N
7.29. Found: C 84.44, H 4.31, N 7.33.
mg, 0.029 mmol). The resulting mixture was stirred in the dark for 2 h.
The solvent was removed under reduced pressure, and the crude
material was purified by flash column chromatography (SiO2, gradient
elution from toluene to 1:19 EtOAc/toluene) and chromatographed a
second time (SiO2, CH2Cl2) to give the product (156 mg, 60%) as a
bright yellow solid. Mp 215−225 °C (decomp). Rf = 0.35 (3:7 THF/
heptane). IR (ATR) νmax (cm−1): 3043w, 3001vw, 2829w, 2730w,
2205w, 2158vw, 1701s, 1598m, 1579sh, 1559w, 1513m, 1431w,
1408m, 1381w. 1H NMR (500 MHz, CDCl3): δ 10.03 (s, 1H), 7.89−
7.87 (m, 2H), 7.75−7.72 (m, 2H), 7.70−7.68 (m, 2H), 7.64−7.61 (m,
2H), 7.56 (s, 4H), 6.93 (s, 1H), 6.59 (dd, J = 11.3, 6.2 Hz, 1H), 6.50
(dd, J = 11.3, 6.0 Hz, 1H), 6.38 (broad d, J = 6.2 Hz, 1H), 6.32 (ddd, J
= 10.2, 6.0, 2.1 Hz, 1H), 5.83 (dd, J = 10.2, 3.9 Hz, 1H), 3.81 (ddd, J =
3.9, 2.1, 2.1 Hz, 1H). 13C NMR (125 MHz, CDCl3): δ 191.5, 139.4,
138.6, 135.7, 133.2, 132.5, 132.3, 131.9, 131.9, 131.4, 131.0, 130.5,
129.4, 127.9, 126.3, 124.7, 123.6, 122.8, 121.7, 119.6, 115.1, 112.7,
93.1, 91.8, 91.2, 90.7, 51.3 (doublet due to incomplete decoupling),
45.2. MALDI-TOF-MS: m/z 484 (M−). Anal. Calcd for C35H20N2O:
C 86.76, H 4.16, N 5.78. Found: C 86.81, H 4.12, N 5.84.
DHA-C60 Conjugate (4). Method 1, Prato reaction. A degassed
mixture of C60 (313 mg, 0.434 mmol), compound 17 (62 mg, 0.161
mmol), and 2-(4-propyloxybenzyl amino)acetic acid (9) (212 mg,
0.910 mmol) in toluene (150 mL) was heated to reflux for 12 h. The
solvent was removed in vacuo, and the crude residue was subjected to
column chromatography (SiO2, gradient elution from CS2 to 3:7
toluene/CS2) to afford the title compound as a dark brown solid (93
mg, 46%). Rf = 0.36 (3:7 toluene/CS2). Method 2, Sonogashira cross-
coupling reaction. A degassed solution of dry NEt3 (2 mL) in toluene
(10 mL) was added via cannula to fulleropyrrolidine aryl-iodide (21)
(13.4 mg, 0.012 mmol), Pd(PPh3)4 (1.4 mg, 0.001 mmol), CuI (0.3
mg, 0.001 mmol), and 25 (17 mg, 0.06 mmol). After 7 h of stirring at
90 °C, the solvent was removed under reduced pressure. The crude
material was purified by column chromatography (SiO2, gradient
elution from CS2 to CH2Cl2) to yield pure title compound as a dark
brown solid (5.1 mg, 33%). IR (ATR) νmax (cm−1): 3017w, 2858w,
2914w, 2867w, 2779w, 1739m, 1602w, 1580w, 1540w, 1507s, 1460m,
1423m, 1409sh, 1372m, 1353 m. 1H NMR (500 MHz, CDCl3): δ 7.95
(broad s, 2H), 7.74−7.71 (m, 2H), 7.65 (broad d, J = 8.1 Hz, 2H),
7.62−7.59 (m, 2H), 7.56−7.54 (m, 2H), 7.04−7.01 (m, 2H), 6.91 (s,
1H), 6.57 (dd, J = 11.3, 5.9 Hz, 1H), 6.49 (dd, J = 11.3, 6.1 Hz, 1H),
6.36 (broad d, J = 5.9 Hz, 1H), 6.31 (ddd, J = 10.2, 6.1, 2.1 Hz, 1H),
5.82 (dd, J = 10.2, 3.8 Hz, 1H), 5.19 (s, 1H), 4.85 (d, J = 9.5 Hz, 1H),
4.49 (d, J = 13.2 Hz, 1H), 4.17 (d, J = 9.5 Hz, 1H), 4.00 (t, J = 6.6 Hz,
2H), 3.79 (ddd, J = 3.8, 2.1, 2.1 Hz, 1H), 3.67 (d, J = 13.2 Hz, 1H),
1.91−1.80 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 158.9, 156.4, 154.2, 153.3, 153.2, 147.5, 146.8, 146.5, 146.5,
146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.1, 146.1, 145.9, 145.7,
145.7, 145.5, 145.4, 145.4, 145.3, 144.9, 144.8, 144.6, 144.5, 143.3,
143.1, 142.8, 142.7, 142.7, 142.7, 142.5, 142.4, 142.3, 142.3, 142.2,
142.2, 142.0, 142.0, 141.8, 141.7, 140.3, 140.3, 140.1, 139.7, 139.5,
138.6, 138.1, 137.1, 136.6, 136.1, 135.8, 133.0, 132.5, 132.3, 131.3,
131.0, 130.3, 130.2, 129.3, 127.9, 126.3, 125.0, 123.1, 121.6, 119.6,
115.1, 114.8, 112.7, 92.1, 89.6, 81.0, 76.7, 69.7, 68.8, 66.6, 56.2, 51.3,
51.2, 45.1, 22.8, 10.8. MALDI-TOF-MS: m/z 1265 (M−). Anal. Calcd
for C98H31N3O: C 92.95, H 2.47, N 3.32. Found: C 92.80, H 2.39, N
3.26.
DHA-C60 Conjugate (5). A degassed mixture consisting of C60
(278 mg, 0.386 mmol), compound 18 (81 mg, 0.167 mmol), and 2-(4-
propyloxybenzyl amino)acetic acid (9) (353 mg, 1.52 mmol) in
toluene (150 mL) was heated to reflux for 12 h. The solvent was
removed in vacuo, and the crude residue was subjected to column
chromatography (SiO2, gradient elution from CS2 to 3:7 toluene/CS2)
to afford the title compound as a dark brown solid (102 mg, 45%). Rf
= 0.38 (3:7 toluene/CS2). IR (ATR) νmax (cm−1): 3019w, 2962w,
2913w, 2868w, 2778w, 1602m, 1581sh, 1507s, 1461m, 1423m, 1409m,
2-{4-[2-(4-(2-(4-Formylphenyl)ethynyl)phenyl)ethynyl]-
phenyl}-1,8a-dihydroazulene-1,1-dicarbonitrile (18). To a de-
gassed stirring solution of compound 2 (205 mg, 0.54 mmol) and 4-
[(4-ethynylphenyl)ethynyl]benzaldehyde (16) (173 mg, 0.75 mmol)
in a solvent mixture of THF (15 mL) and diisopropylamine (10 mL)
were added sequentially CuI (10 mg, 0.053 mmol) and Pd(PPh3)4 (33
1
1372m, 1352w. H NMR (500 MHz, CDCl3): δ 7.94 (broad s, 2H),
7.74−7.71 (m, 2H), 7.65 (broad d, J = 8.1 Hz, 2H), 7.62−7.59 (m,
2H), 7.56−7.50 (m, 6H), 7.04−7.01 (m, 2H), 6.92 (s, 1H), 6.58 (dd, J
= 11.2, 5.9 Hz, 1H), 6.49 (dd, J = 11.2, 6.1 Hz, 1H), 6.37 (broad d, J =
5.9 Hz, 1H), 6.32 (ddd, J = 10.2, 6.1, 2.1 Hz, 1H), 5.83 (dd, J = 10.2,
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3.8 Hz, 1H), 5.18 (s, 1H), 4.85 (d, J = 9.5 Hz, 1H), 4.49 (d, J = 13.2
Hz, 1H), 4.17 (d, J = 9.5 Hz, 1H), 4.00 (t, J = 6.6 Hz, 2H), 3.80 (ddd,
J = 3.8, 2.1, 2.1 Hz, 1H), 3.67 (d, J = 13.2 Hz, 1H), 1.90−1.82 (m,
2H), 1.08 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 158.9,
156.5, 154.2, 153.3, 153.2, 147.5, 147.5, 146.8, 146.5, 146.5, 146.4,
146.4, 146.3, 146.3, 146.3, 146.2, 146.1, 146.1, 145.9, 145.7, 145.7,
145.5, 145.5, 145.4, 145.4, 145.3, 144.9, 144.8, 144.6, 144.5, 143.3,
143.1, 142.8, 142.7, 142.7, 142.7, 142.5, 142.4, 142.3, 142.3, 142.2,
142.2, 142.2, 142.0, 142.0, 141.8, 141.7, 140.3, 140.3, 140.1, 139.7,
139.5, 138.6, 137.1, 136.6, 136.1, 135.8, 133.1, 132.5, 131.8, 131.7,
131.3, 131.0, 130.3, 130.3, 129.3, 127.9, 126.3, 124.9, 123.5, 123.3,
122.9, 121.6, 119.6, 115.1, 114.8, 112.7, 92.0, 91.4, 90.8, 90.0, 81.0,
81.0, 76.8, 69.7, 68.8, 66.6, 56.2, 51.3, 51.2, 45.2, 22.8, 10.8. MALDI-
TOF-MS: m/z 1365 (M−). Anal. Calcd for C106H35N3O: C 93.17, H
2.58, N 3.08. Found: C 93.09, H 2.68, N 3.01.
elution from CS2 to 1:19 toluene/CS2) to afford the title compound as
a dark brown solid (2.2 mg, 29%). Rf = 0.31 (1:19 toluene/CS2). IR
(ATR) νmax (cm−1): 3032vw, 2958w, 2932w, 2786w, 2152m, 1611w,
1583vw, 1537s, 1510m, 1464m, 1426m, 1371m, 1353m, 1333m,
1
1297m, 1246vs. H NMR (500 MHz, CDCl3): δ 7.88 (broad s, 2H),
7.57 (broad d, J = 8.0 Hz, 4H), 7.53−7.50 (m, 2H), 7.04−6.98 (m,
2H), 5.14 (s, 1H), 4.83 (d, J = 9.5 Hz, 1H), 4.44 (d, J = 13.2 Hz, 1H),
4.16 (d, J = 9.5 Hz, 1H), 3.99 (t, J = 6.5 Hz, 2H), 3.65 (d, J = 13.2 Hz,
2H), 1.89−1.82 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H), 0.24 (s, 9H). 13C
NMR (125 MHz, CDCl3): δ 158.8, 156.4, 154.2, 153.3, 153.2, 147.5,
146.8, 146.5, 146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.2, 146.1,
146.1, 145.9, 145.7, 145.6, 145.5, 145.5, 145.4, 145.4, 145.4, 145.3,
144.9, 144.8, 144.5, 144.5, 143.3, 143.1, 142.8, 142.7, 142.7, 142.7,
142.5, 142.4, 142.3, 142.3, 142.2, 142.0, 142.0, 141.8, 141.7, 140.3,
140.2, 140.0, 139.7, 137.9, 137.1, 136.6, 136.1, 135.8, 132.6, 130.3,
123.3, 114.8, 95.2, 80.9, 76.7, 69.8, 68.8, 66.6, 56.1, 22.8, 10.8, 0.1.
MALDI-TOF-MS: m/z 1083 (M−). Anal. Calcd for C83H29NOSi: C
91.95, H 2.70, N 1.29. Found: C 92.03, H 2.65, N 1.16.
Fulleropyrrolidine Aryl-iodide (21). To a degassed solution of
C60 (200 mg, 0.28 mmol) in dry toluene (150 mL) were added 2-(4-
propoxybenzylamino)acetic acid (9) (375 mg, 1.62 mmol) and 4-
iodobenzaldehyde (19) (78 mg, 0.34 mmol). The contents of the
reaction vessel were refluxed for 2 h. The solvent was removed in
vacuo, and the crude residue was purified by column chromatography
(SiO2, gradient elution from CS2 to 1:4 toluene/CS2) to yield the title
compound 21 as a dark brown solid (122 mg, 39%). Rf = 0.33 (1:19
toluene/CS2). IR (ATR) νmax (cm−1): 2954w, 2912w, 2868w, 2779w,
1606m, 1580m, 1507vs, 1479s, 1461s, 1423s, 1402m, 1371m, 1352m,
2-[4-(Triisopropylsilylethynyl)phenyl]-1,8a-dihydroazulene-
1,1-dicarbonitrile (24). To a mixture of compound 2 (200 mg, 0.52
mmol), PdCl2(PPh3)2 (20 mg, 0.026 mmol), and CuI (10 mg, 0.053
mmol) was added a degassed solution of triisopropylsilylacetylene
(0.24 mL, 1.05 mmol) in (i-Pr)2NH (0.2 mL) and THF (10 mL), and
the mixture was stirred in darkness for 3 h at rt. The solvent was
removed under reduced pressure, the residue was extracted with
minimal toluene and filtered through cotton wool, and the solvent was
removed in vacuo. The crude residue was purified by dry column
chromatography (SiO2, 80 mL fractions, gradient elution starting with
heptane and increasing the CH2Cl2 content by 3 mL per fraction). The
first yellow band yielded the title compound 24 as a yellow crystalline
solid (168 mg, 74%). Rf = 0.53 (1:1 CH2Cl2/heptane). Mp 131.5−
133.0 °C. IR (ATR) νmax (cm−1): 3020w, 2944s, 2892m, 2864s,
1
1333m, 1231vs, 1165vs. H NMR (500 MHz, CDCl3): δ 7.82 (broad
d, J = 7.9 Hz, 2H), 7.70 (broad s, 2H), 7.58−7.50 (m, 2H), 7.07−6.99
(m, 2H), 5.13 (s, 1H), 4.86 (d, J = 9.6 Hz, 1H), 4.46 (d, J = 13.2 Hz,
1H), 4.17 (d, J = 9.6 Hz, 1H), 4.02 (t, J = 6.5 Hz, 2H), 3.66 (d, J =
13.2 Hz, 1H), 1.92−1.85 (m, 2H), 1.10 (t, J = 7.4 Hz, 3H).13C NMR
(125 MHz, CDCl3): δ 158.8, 156.4, 154.1, 153.2, 153.1, 147.5, 147.4,
146.7, 146.5, 146.4, 146.3, 146.3, 146.3, 146.2, 146.1, 146.1, 146.1,
145.8, 145.7, 145.6, 145.6, 145.5, 145.5, 145.4, 145.4, 145.3, 144.8,
144.7, 144.5, 144.5, 143.3, 143.1, 142.8, 142.7, 142.7, 142.5, 142.3,
142.3, 142.2, 142.1, 142.1, 142.0, 141.8, 141.7, 140.3, 140.3, 140.1,
139.7, 138.1, 137.1, 137.1, 136.5, 136.1, 135.8, 131.5, 130.2, 129.2,
114.8, 94.5, 80.7, 76.5, 69.7, 68.7, 66.6, 56.2, 22.8, 10.8. MALDI-TOF-
MS: m/z 1113 (M−). Anal. Calcd for C78H20NIO: C 84.09, H 1.81, N
1.26. Found: C 84.19, H 1.73, N 1.35.
Fulleropyrrolidine Aryl-ethynyl (22). To a degassed solution of
C60 (200 mg, 0.28 mmol) in dry toluene (150 mL) were added 2-(4-
propoxybenzylamino)acetic acid (9) (375 mg, 1.62 mmol) and 4-
ethynylbenzaldehyde (20) (72 mg, 0.56 mmol). The resulting mixture
was refluxed for 4 h. The solvent was removed in vacuo, and the crude
material was purified by column chromatography (SiO2, gradient
elution from CS2 to 1:4 toluene/CS2) to give the title compound as a
brown solid (147 mg, 53%). Rf = 0.30 (1:19 toluene/CS2). IR (ATR)
νmax (cm−1): 3288w, 2913w, 2868w, 2774w, 2194vw, 1672w, 1605w,
1573w, 1506s, 1461m, 1422m, 1371w, 1333w, 1296w, 1224s, 1168s.
1H NMR (500 MHz, CDCl3): δ 7.90 (broad s, 2H), 7.60 (broad d, J =
8.2 Hz, 2H), 7.54−7.51 (m, 2H), 7.04−6.98 (m, 2H), 5.16 (s, 1H),
4.84 (d, J = 9.5 Hz, 1H), 4.46 (d, J = 13.2 Hz, 1H), 4.16 (d, J = 9.5 Hz,
1H), 3.99 (t, J = 6.6 Hz, 2H), 3.65 (d, J = 13.2 Hz, 1H), 3.10 (s, 1H),
1.89−1.82 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 158.9, 156.4, 154.2, 153.2, 153.1, 147.5, 147.5, 146.8, 146.5,
146.4, 146.4, 146.4, 146.3, 146.3, 146.3, 146.1, 146.1, 146.1, 145.9,
145.7, 145.7, 145.6, 145.6, 145.5, 145.5, 145. 5, 145.4, 145.4, 145.3,
144.9, 144.8, 144.6, 144.5, 143.3, 143.1, 142.8, 142.7, 142.7, 142.7,
142.5, 142.4, 142.3, 142.3, 142.2 142.1, 142.0, 142.0, 141.8, 141.7,
140.3, 140.3, 140.0, 139.7, 138.2, 137.1, 136.6, 136.1, 135.8, 132.7,
130.3, 122.4, 114.7, 83.5, 80.9, 78.0, 76.7, 69.7, 68.8, 66.6, 56.2, 22.8,
10.8. MALDI-TOF-MS: m/z 1011 (M−). Anal. Calcd for C80H21NO:
C 94.94, H 2.09, N 1.38. Found: C 94.80, H 2.21, N 1.32.
1
2240vw, 2156m, 1599m, 1505m, 1462s, 1411m, 1387m, 1366 m. H
NMR (500 MHz, CDCl3): δ 7.69−7.66 (m, 2H), 7.57−7.55 (m, 2H),
6.89 (s, 1H), 6.57 (dd, J = 11.3, 6.2 Hz, 1H), 6.48 (dd, J = 11.3, 6.0
Hz, 1H), 6.36 (broad d, J = 6.2 Hz, 1H), 6.31 (ddd, J = 10.2, 6.0, 2.1
Hz, 1H), 5.82 (dd, J = 10.1, 3.8 Hz, 1H), 3.79 (ddd, J = 3.8, 2.1, 2.1
Hz, 1H), 1.21−1.03 (m, 21H). 13C NMR (125 MHz, CDCl3): δ 139.5,
138.6, 133.0, 132.9, 131.2, 131.0, 130.2, 127.8, 126.1, 125.3, 121.5,
119.6, 115.1, 112.7, 106.3, 94.2, 51.2 (doublet signal due to incomplete
decoupling), 45.2, 18.8, 11.4, 1C masked. ES-MS (MeOH): m/z 437
([M + H]+). Anal. Calcd for C29H32N2Si: C 79.77, H 7.39, N 6.42.
Found: C 79.57, H 7.40, N 6.36.
2-(4-Ethynylphenyl)-1,8a-dihydroazulene-1,1-dicarbonitrile
(25). Method 1. To a solution of 24 (289 mg, 0.663 mmol) in THF
(30 mL) were added AcOH (0.38 mL 6.6 mmol) and a solution of
Bu4NF (1.33 mL, 1.33 mmol, 1 M) in THF dropwise. The reaction
mixture was refluxed for 16 h (resulting in a light yellow-brown color),
after which it was diluted with Et2O (50 mL), washed with water (3 ×
50 mL), dried with Na2SO4, filtered, and concentrated in vacuo.
Purification by dry column vacuum chromatography (SiO2, 12.6 cm2,
0−70% toluene/heptanes, 5% steps, then 70−80% toluene/heptanes,
2.5% steps, 40 mL fractions) gave 25 (137 mg, 76%) as a yellow solid.
For the alternative methods described in Scheme 7, see the Supporting
Information. Rf = 0.24 (50% toluene/heptanes); Rf = 0.50 (80%
toluene/heptanes); Rf = 0.31 (1:1 CH2Cl2/heptane). Mp 143.0−143.5
°C. IR (ATR) νmax (cm−1): 3280s, 3016w, 2954sh, 2922m, 2851m,
2244w, 2202vw, 1725w, 1602w, 1579w, 1504m, 1462m, 1411m,
1
1382w. H NMR (500 MHz, CDCl3): δ 7.71−7.68 (m, 2H), 7.59−
7.57 (m, 2H), 6.91 (s, 1H), 6.58 (dd, J = 11.2, 6.3 Hz, 1H), 6.49 (dd, J
= 11.2, 6.1 Hz, 1H), 6.37 (broad d, J = 6.3 Hz, 1H), 6.31 (ddd, J =
10.2, 6.1, 2.1 Hz, 1H), 5.82 (dd, J = 10.2, 3.8 Hz, 1H), 3.79 (ddd, J =
3.8, 2.1, 2.1 Hz, 1H), 3.22 (s, CCH 1H). 13C NMR (125 MHz,
CDCl3): δ 139.3, 138.5, 133.3, 133.0, 131.4, 131.0, 130.8, 127.9, 126.2,
123.9, 121.8, 119.6, 115.1, 112.7, 83.0, 79.9 (doublet signal due to
incomplete decoupling), 51.2 (doublet signal due to incomplete
decoupling), 45.2, 1C masked. ES-MS: m/z 303 ([M + Na]+). Anal.
Calcd for C20H12N2: C 85.69, H 4.31, N 9.99. Found: C 85.60, H 4.15,
N 9.90.
Fulleropyrrolidine Derivative (23). To a mixture of compound
21 (8 mg, 0.007 mmol), Pd(PPh3)4 (1 mg, 0.0009 mmol), and CuI
(0.1 mg, 0.0005 mmol) was added a degassed solution of
trimethylsilylacetylene (0.1 mL) and NEt3 (2 mL) in toluene (10
mL). The reaction contents were stirred for 6 h at 90 °C, after which
time the solvent was removed under reduced pressure. The crude
residue was subsequently purified by chromatography (SiO2, gradient
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The Journal of Organic Chemistry
Article
2-{1-[4-(Trimethylsilylethynyl)phenyl]ethylidene}-
malononitrile (27). A mixture consisting of 4-(trimethylsilyl)ethynyl
acetophenone (26) (3.79 g, 17.5 mmol), malononitrile (3.45 g, 52.3
mmol), and ammonium acetate (4.52 g, 58.7 mmol) in toluene (150
mL) and AcOH (6 mL) was refluxed for 2 h. The vessel was allowed
to cool to rt, and the upper phase was decanted and washed with water
(2 × 200 mL). The organic phase was dried over MgSO4 and filtered,
and the solvent was removed under reduced pressure. The crude
residue was purified by column chromatography (SiO2, 3:17 EtOAc/
heptanes) to afford the title compound 27 as a white solid (4.16 g,
90%). Mp 71−72 °C. Rf = 0.33 (3:17 EtOAc/heptanes). IR (ATR)
νmax (cm−1): 2956w, 2901w, 2224m, 2159m, 1599m, 1576s, 1544m,
vacuo. The yellow solid was redissolved in CCl4 (25 mL), washed with
saturated aqueous NaS2O3 (10 mL) and saturated aqueous NaHCO3
(3 × 20 mL), dried with MgSO4, filtered, and concentrated in vacuo,
which gave 31 (121 mg, 92%) as an essentially pure yellow crystalline
solid. Rf = 0.58 (80% toluene/heptanes). 1H NMR (500 MHz,
CDCl3): δ 7.68 (d, J = 8.7 Hz, 2H), 7.53 (d, J = 8.7 Hz, 2H), 6.90 (s,
1H), 6.57 (dd, J = 11.2, 6.3 Hz, 1H), 6.49 (dd, J = 11.2, 6.1 Hz, 1H),
6.37 (broad d, J = 6.3, Hz, 1H), 6.31 (ddd, J = 10.2, 6.1, 2.1 Hz, 1H),
5.81 (broad d, J = 10.2, 3.8 Hz, 1H), 3.79 (ddd, J = 3.8, 2.1, 2.1 Hz,
1H) ppm. 13C NMR (125 MHz, CDCl3): δ 139.3, 138.6, 133.3, 132.9,
131.4, 131.0, 130.6, 127.9, 126.2, 124.5, 121.8, 119.6, 115.1, 112.7,
79.6, 53.1, 51.2, 45.2. HR-MS (ESP+): m/z 380.9990/382.9979 ([M +
Na]+) (Br79/81); calcd for C20H11Br79/81N2Na+: m/z 380.9998/
382.9978.
1
1499m, 1408m, 1373 m. H NMR (500 MHz, CDCl3): δ 7.58−7.54
(m, 2H), 7.53−7.48 (m, 2H), 2.62 (s, 3H), 0.26 (s, 9H). 13C NMR
(125 MHz, CDCl3): δ 174.2, 135.5, 132.6, 127.6, 127.5, 112.8, 103.6,
98.8, 85.0, 24.2, 24.2, 24.2, 24.1, −0.08. ES-MS: m/z 287 ([M + Na]+).
Anal. Calcd for C16H16N2Si: C 72.68, H 6.10, N 10.60. Found: C
72.44, H 6.08, N 10.57.
DHA-C60 Conjugate (6). Method 1. To a solution of compounds
25 (72 mg, 0.26 mol) and 22 (76 mg, 0.075 mmol) in chlorobenzene
(20 mL) were added CuCl (180 mg, 1.81 mmol) and TMEDA (0.5
mL) under an oxygen atmosphere, by the use of a balloon. The
contents were stirred for 2 h at rt after which time the solution was
passed through a short pad of silica gel. The solvent was removed, and
the crude mixture was purified by column chromatography (SiO2,
gradient elution from CS2 to 1:1 CS2/toluene). The second
component to elute from the column was identified as the title
compound, which was isolated pure as a dark brown solid (25 mg,
26%). Rf = 0.38 (2:3 toluene/CS2). IR (ATR) νmax (cm−1): 3014vw,
2912w, 2867w, 2779w, 1603m, 1580m, 1507s, 1461m, 1424m, 1408m,
2-{(2-Cyclohepta-2,4,6-trienyl)-1-[4-(trimethylsilylethynyl)-
phenyl]ethylidene}malononitrile (28). To a rapidly stirring
suspension of tropylium tetrafluoroborate (2.89 g, 16.3 mmol) and
dicyano compound 27 (3.90 g, 14.8 mmol) in dry CH2Cl2 (100 mL)
at −78 °C, under an argon atmosphere, was added NEt3 (2.4 mL, 17.0
mmol) during the course of 1 h. The contents were allowed to stir a
further 10 min and aqueous 2 M HCl (20 mL) was added to the cold
vessel after which time the cold bath was removed and the vessel was
allowed to reach rt. The organic phase was washed twice with water,
dried over MgSO4, and filtered, and the solvent was removed in vacuo.
The crude residue was purified by column chromatography (SiO2,
3:17 EtOAc/heptanes) to afford the title compound 28 (4.90 g, 85%)
as a yellowish oil. Rf = 0.38 (3:17 EtOAc/heptane). IR (neat) νmax
(cm−1): 3021w, 2960m, 2900w, 2230m, 2160m, 1602m, 1577m,
1
1373m, 1351m, 1333m, 1297m, 1224s, 1170s. H NMR (500 MHz,
CDCl3): δ 7.93 (broad s, 2H), 7.71−7.69 (m, 2H), 7.64 (broad d, J =
8.1 Hz, 2H), 7.61−7.58 (m, 2H), 7.55−7.52 (m, 2H), 7.04−7.01 (m,
2H), 6.92 (s, 1H), 6.58 (dd, J = 11.3, 6.0 Hz, 1H), 6.50 (dd, J = 11.3,
6.1 Hz, 1H), 6.37 (broad d, J = 6.0 Hz, 1H), 6.31 (ddd, J = 10.2, 6.1,
2.1 Hz, 1H), 5.82 (dd, J = 10.2, 3.8 Hz, 1H), 5.18 (s, 1H), 4.84 (d, J =
9.5 Hz, 1H), 4.46 (d, J = 13.2 Hz, 1H), 4.16 (d, J = 9.5 Hz, 1H), 4.00
(t, J = 6.6 Hz, 2H), 3.79 (ddd, J = 3.8, 2.1, 2.1 Hz, 1H), 3.66 (d, J =
13.2 Hz, 1H), 1.90−1.81 (m, 2H), 1.08 (t, J = 7.4 Hz, 3H). 13C NMR
(125 MHz, CDCl3): δ 158.9, 156.4, 154.1, 153.1, 153.0, 147.5, 147.5,
146.7, 146.5, 146.5, 146.4, 146.4, 146.3, 146.3, 146.3, 146.1, 146.1,
146.0, 145.8, 145.7, 145.7, 145.6, 145.6, 145.5, 145.5, 145.4, 145.4,
145.3, 144.9, 144.8, 144.6, 144.5, 143.3, 143.1, 142.8, 142.7, 142.7,
142.7, 142.5, 142.4, 142.3, 142.3, 142.2, 142.1, 142.0, 141.8, 141.7,
140.3, 140.3, 140.0, 139.7, 139.2, 139.1, 138.5, 137.1, 136.5, 136.1,
135.8, 133.6, 133,4, 133.1, 131.5, 131.1, 131.0, 130.3, 127.9, 126.3,
123.5, 122.0, 121.9, 119.6, 115.0, 114.8, 112.6, 82.9, 81.2, 80.9, 80.9,
76.7, 76.7, 74.7, 69.7, 68.8, 66.6, 56.3, 51.2, 51.2, 45.1, 22.8, 10.8.
MALDI-TOF-MS: m/z 1289 (M−). Anal. Calcd for C100H31N3O: C
93.08, H 2.42, N 3.26. Found: C 92.89, H 2.33, N 3.17. Method 2. A
degassed solution of NEt3 (0.05 mL, mmol) in dry THF (15 mL) was
added via cannula to a stirring mixture of 22 (56 mg, 0.055 mmol), 31
(20 mg, 0.056 mmol), Pd(PPh3)4 (4 mg, 0.0035 mmol), and CuI (1
mg, 0.005 mmol), and the resulting solution was heated by means of
microwave to 70 °C for 10 h. The solvent was removed in vacuo, and
the crude residue was purified by column chromatography (SiO2,
gradient elution 10% toluene/CS2 to 40% toluene/CS2) to afford the
product 6 as a dark brown powder (27 mg, 38%).
1
1542w, 1499w. H NMR (500 MHz, CDCl3): δ 7.56−7.52 (m, 2H),
7.38−7.33 (m, 2H), 6.60−6.58 (m, 2H), 6.20−6.17 (m, 2H), 5.12 (dd,
J = 9.1, 6.4 Hz, 2H), 3.18 (d, J = 8.0 Hz, 2H), 1.96−1.90 (m, 2H), 0.26
(s, 9H). 13C NMR (125 MHz, CDCl3): δ 177.2, 134.3, 132.7, 131.3,
127.4, 127.2, 126.6, 122.8, 112.5, 103.6, 98.5, 86.7, 38.9, 37.9, −0.08.
ES-MS: m/z 393 ([M + K]+), 377 ([M + Na]+). HR-MS (ES+): m/z
377.1439 ([M + Na]+); calcd for C23H22N2NaSi+ m/z 377.1444.
2-[4-(Trimethylsilylethynyl)phenyl)]-1,8a-dihydroazulene-
1,1-dicarbonitrile (29). A mixture of cycloheptatriene compound 28
(4.21 g, 11.9 mmol) and tritylium tetrafluoroborate (4.12 g, 12.5
mmol) in dry CH2Cl2 (200 mL) was allowed to stir at rt for 16 h. The
vessel was cooled in an ice bath, and then the mixture was treated with
NEt3 (1.8 mL, 12.8 mmol) and allowed to reach rt. The solvent was
removed in vacuo, and MeCN (50 mL) was added to the flask, which
was maintained at 50 °C for 30 min. The solvent was removed under
reduced pressure, and the crude residue was purified by column
chromatography (SiO2, 1:1 CH2Cl2/heptanes) to afford the title
compound as a glassy yellow solid (2.02 g, 48%). Rf = 0.36 (1:1
CH2Cl2/heptanes). Mp 59−62 °C. IR (ATR) νmax (cm−1): 3020w,
2958m, 2898w, 2249w, 2201w, 2155s, 1600w, 1584w, 1505s, 1409m,
1
1390sh. H NMR (500 MHz, CDCl3): δ 7.68−7.66 (m, 2H), 7.55−
7.53 (m, 2H), 6.90 (s, 1H), 6.57 (dd, J = 11.3, 6.2 Hz, 1H), 6.49 (dd, J
= 11.3, 6.1 Hz, 1H), 6.36 (broad d, J = 6.2 Hz, 1H), 6.31 (ddd, J =
10.2, 6.1, 2.1 Hz, 1H), 5.81 (dd, J = 10.2, 3.8 Hz, 1H), 3.79 (ddd, J =
3.8, 2.1, 2.1 Hz, 1H), 0.27 (s, 9H). 13C NMR (126 MHz, CDCl3): δ
139.5, 138.6, 133.1, 132.8, 131.3, 131.0, 130.4, 127.8, 126.1, 125.0,
121.6, 119.6, 115.1, 112.7, 104.3, 97.6, 51.3 (doublet signal due to
incomplete decoupling), 45.2, 0.0. MALDI-TOF-MS: m/z 352 (M−).
Anal. Calcd for C23H20N2Si: C 78.38, H 5.72, N 7.95. Found: C 78.55,
H 5.68, N 7.81.
ASSOCIATED CONTENT
■
S
* Supporting Information
Different experimental procedures for synthesis of 25, X-ray
crystal structure of compound 17, and further details on the
complex between DHA 2 and C60, photolysis and thermal
switching studies, UV−vis absorption and NMR spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
2-(4′-Bromoethynylphenyl)-1,8a-dihydroazulene-1,1-dicar-
bonitrile (31). To a stirred solution of 25 (102 mg, 0.364 mmol) in
acetone (30 mL) were added NBS (102 mg, 0.573 mmol) and AgNO3
(19 mg, 0.11 mmol, 30 mol %), and the solution was stirred at rt for
20 min. The yellow reaction mixture became milky since a white-
yellow precipitate was formed. Water (50 mL) was added, the mixture
was extracted with CH2Cl2 (100 mL), and the extract was washed with
water (3 × 50 mL), dried with MgSO4, filtered, and concentrated in
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: mbn@kiku.dk.
8931
dx.doi.org/10.1021/jo301306y | J. Org. Chem. 2012, 77, 8922−8932

The Journal of Organic Chemistry
Article
Geskin, V.; Cornil, J.; Bjørnholm, T.; Nielsen, M. B. J. Org. Chem.
2011, 76, 245−263.
Notes
The authors declare no competing financial interest.
(11) (a) Maggini, M.; Scorrano, G.; Prato, M. J. Am. Chem. Soc. 1993,
115, 9798−9799. (b) Maggini, M.; Scorrano, G.; Bianco, A.; Toniolo,
C.; Sijbesma, R. P.; Wudl, F.; Prato, M. J. Chem. Soc., Chem. Soc. 1994,
305−306. (c) Prato, M.; Maggini, M.; Giacometti, C.; Scorrano, G.;
ACKNOWLEDGMENTS
■
We acknowledge The Lundbeck Foundation and the Sino-
Danish Center for Education and Research (SDC) for financial
support.
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