One-pot thermally chemocontrolled double Diels-Alder strategies. A route to [4 + 2] functionalisation/[4 + 2] derivatization of C60

Article abstract of DOI:10.1039/c3ra23327h

The one-pot double Diels-Alder reactions of 3,4-di(methylene) tetrahydrothiophene-1,1-dioxide using temperature as the only chemocontrol element are described. Zn-dust promoted the 1,4-debromination of 3,4-bis(bromomethyl)-2,5-dihydrothiophene-1,1-dioxide in 5-nonanone, under MW conditions, followed by a Diels-Alder reaction, an SO₂ extrusion step and a second Diels-Alder reaction. This approach was applied successfully in double [4 + 2] cycloadditions using the same or two different dienophiles to afford the corresponding Diels-Alder products in excellent yields. An elegant and practical method for [4 + 2] functionalisation/[4 + 2] derivatization of C₆₀ was achieved in a one-pot manner via the formation of a new reactive C₆₆ dienic intermediate.

Full text of DOI:10.1039/c3ra23327h

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One-pot thermally chemocontrolled double Diels–Alder
strategies. A route to [4 + 2] functionalisation/[4 + 2]
derivatization of C 3
Cite this: RSC Advances, 2013, 3,
4
750
6
0
Marios S. Markoulides, Georgios I. Ioannou, Manolis J. Manos and Nikos Chronakis*
The one-pot double Diels–Alder reactions of 3,4-di(methylene)tetrahydrothiophene-1,1-dioxide using
temperature as the only chemocontrol element are described. Zn-dust promoted the 1,4-debromination of
3
,4-bis(bromomethyl)-2,5-dihydrothiophene-1,1-dioxide in 5-nonanone, under MW conditions, followed
by a Diels–Alder reaction, an SO extrusion step and a second Diels–Alder reaction. This approach was
2
Received 14th December 2012,
Accepted 30th January 2013
applied successfully in double [4 + 2] cycloadditions using the same or two different dienophiles to afford
the corresponding Diels–Alder products in excellent yields. An elegant and practical method for [4 + 2]
functionalisation/[4 + 2] derivatization of C60 was achieved in a one-pot manner via the formation of a
new reactive C66 dienic intermediate.
DOI: 10.1039/c3ra23327h
www.rsc.org/advances
based tetrathiafulvalene (TTF) adducts for photovoltaic devices
Introduction
1
0
were unsuccessful. The possibility of developing dienic
chemistry in the TTF series was not possible until two
different strategies were presented by the groups of
In the past two decades, the chemical functionalisation of
fullerenes has been mainly devoted to the production of stable
1
derivatives for applications in materials science and medic-
11
12
Hudhomme and Rovira. As far as further derivatization
2
3
inal chemistry. Inspired by the unique photophysical and
of C60 cycloadducts is concerned, there are relatively limited
4
electrochemical properties of [60]fullerene, chemists have
5b,13
methods reported.
Usually, competing side reactions lead
developed elegant methodologies for the covalent attachment
of a wide variety of addends onto the C60 sphere targeting
materials of high technological interest. The Diels–Alder
reaction has attracted particular attention and a plethora of
to the formation of undesirable fullerene products rendering
the isolation of the desired C60 adducts quite a difficult task.
In light of the limitations posed by the current methods for
the [4 + 2] functionalisation of C60 and the subsequent
derivatization of the fullerene cycloadducts, as well as, by the
relatively limited examples which utilise precursors of the
[
4 + 2] fullerene cycloadducts have been reported in the
5
literature synthesised under thermal (conventional heating,
6
microwave irradiation) conditions. The reversibility of the
Diels–Alder reaction has been demonstrated by using cyclo-
7
7b,8
7b
pentadiene,
9
anthracene,
1,3-diphenylisobenzofuran,
9
9
-methylanthracene and 9,10-dimethylanthracene as dienes.
These examples proved that the potential of such reactions for
the synthesis of stable C60 derivatives is restricted due to the
facile cycloreversion to the starting materials.
The [4 + 2] C60 adducts are generally obtained from
precursors which have the dienic structure 2 (Scheme 1) and
are attached to the dienophilic C in the last step of the
6
0
5
sequence. This strategy requires the preparation of new diene
or masked-diene intermediates which usually necessitates
multistep synthesis. For example, attempts to prepare C -
6
0
Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678, Nicosia,
Cyprus. E-mail: nchronak@ucy.ac.cy; Fax: +357 22892801; Tel: +357 22892781
1
13
3
Electronic supplementary information (ESI) available: Copies of H and
C
NMR spectra, high resolution mass spectra, TGA, DSC data. CCDC 886629 and
86630. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ra23327h
Scheme 1 Strategies for C60 functionalisation/derivatization via the Diels–Alder
8
reaction.
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transient intermediate 2,29-bisallyl diradical 4, we envisioned
the use of precursors 5 or 6 (Scheme 1) for a thermally
chemocontrolled double Diels–Alder process in a stepwise or
in a one-pot manner. The advantages of such a strategy are: a)
the generation of the diene intermediate 3 either in a stepwise
or in a one-pot manner; (b) the utilisation of temperature as
the only chemocontrol element; and (c) the quick synthetic
access to a large number of C60 polycyclic compounds by using
simple dienophiles with a wide range of chemical functional-
ities.
Results and discussion
To explore the use of a thermally reactive bis-diene precursor
of 2,29-bisallyl diradical 4, we focused our initial attempts on
the conversion of the dibromo derivative 6 to the hybrid
molecule 5 equipped with a sulfone and a sultine group
1
4
(
Scheme 2). As it is evident from literature examples, sultine
derivatives open up at lower temperatures relative to sulfones.
However, the nature of substituents present in the precursors
seems to influence the temperature required for the genera-
tion of the diene moiety. Dittmer and co-workers reported the
high yield synthesis of a sultine derivative starting from an
o-xylylene dibromide precursor, under phase-transfer catalyst
Scheme 3 Stepwise Diels–Alder strategies via thermal SO
2
extrusion.
(
PTC) conditions and by using sodium hydroxymethanesulfi-
1
5
nate (Rongalite). Rongalite is used as a decolorizing agent in
1
6
textile industry but only a few reports are available in the
literature demonstrating its utility in organic synthesis. The
preparation of dibromo-sulfone 6 was performed following a
acetylenedicarboxylate (DMAD) as the dienophile (Scheme 3).
Products 9 and 12 were isolated as colorless solids in 83% and
87%, respectively. Suitable single crystals of 12 were easily
obtained by recrystallization from ethanol. The proposed
structure was unambiguously confirmed by X-ray crystal-
lography (Fig. 1). The Diels–Alder adducts 9 and 12 were
slightly contaminated with the oxidized forms 10 and 13
respectively and therefore, the procedures were repeated
1
7,18
literature procedure.
Attempts to synthesise 5, following
1
5
the procedure of Dittmer, were not successful despite the
extensive experimentation and modification of the reaction
conditions. The diene-sulfone 7 was the sole product of the
reaction in all cases (Scheme 2).
Our investigation was then focused on the sulfone
followed by the in situ oxidation of 9 and 12 with MnO
afford 10 and 13 in 81% and 86%, respectively (Scheme 3).
2
to
1
8
derivatives 6 and 11 (Scheme 3). These diene precursors
are useful building blocks for the construction of complex
polycyclic compounds via a simplified route involving first a
Following the traditional strategy for C60 functionalisation
(Scheme 1), sulfone 11 was employed in a [4 + 2] cycloaddition
with C60. The reaction was performed in o-DCB solvent, at 170–
180 uC for 30 min to afford monoadduct 14 which was isolated
in 59% yield after purification by column chromatography on
silica gel (toluene–EtOAc = 20 : 1) and precipitation from
thermal SO
reaction. Studies of 6 and 11 by thermogravimetric analysis
TGA) and differential scanning calorimetry (DSC) showed
similar decomposition peak temperatures starting at around
70 uC (see ESI ). The Diels–Alder reactions of 6 and 11 were
subsequently performed in diphenyl ether (Ph O) solvent, at
70–180 uC for 30 min, using an excess of dimethyl
2
extrusion and then a [4 + 2] cycloaddition
(
1
3
CHCl –pentane (Scheme 3). Monoadduct 14 was characterised
3
1
13
by H and C NMR spectroscopy and by MALDI-TOF mass
2
1
1
3
spectrometry (see ESI ). The H NMR spectrum of 14 showed
two broad singlets at 3.94 and 3.51 ppm which correspond to
Scheme 2 Attempted preparation of the masked bis-diene 5.
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Fig. 1 X-ray crystal structures of 12 (left) and 16 (right).
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the methylenic hydrogens of the cyclohexene rings and a
broad singlet at 3.77 ppm attributed to the methyl hydrogens
and therefore, we examined the reaction under microwave
irradiation. Interestingly, using MW conditions, the prepara-
tion of 11 in 5-nonanone was quantitative with no signs of
decomposition. Upon completion of the 1,4-debromination
step and the first Diels–Alder cycloaddition, the reaction
mixture was transferred in a round-bottomed flask and the
temperature was raised at 170–180 uC for 30 min to afford
adduct 12 in 83% overall yield starting from 6 (Table 1, entry
5). Alternatively, the stepwise procedure for the preparation of
1
3
of the ester groups. In the C NMR spectrum, four signals at
5.74, 52.26, 43.65, 30.67 ppm were observed corresponding to
6
3
the sp carbon atoms of the fullerene skeleton and the organic
addend. In the region between 129.62–156.15 ppm, 17 peaks
2
were present attributed to the fullerene sp carbons and the
carbons of the double bonds of the cyclohexene rings thus
indicating a C -symmetrical structure. Finally, the high
2
v
1
8
resolution MALDI-TOF mass spectra (negative mode, DCTB
12 from 6 proceeded in two steps and 80% overall yield.
as the matrix) of the fullerene monoadduct 14 showed the [M
2,3,6,7-Tetrasubstituted 1,4,5,8-tetrahydronaphthalene 12 has
been prepared previously either in a four step sequence
starting from 1,4-dibromo-2,3-bis(bromomethyl)but-2-ene in
2
2
4H] ion at m/z 938.0575 Da.
Next we examined the possibility of promoting the 1,4-
1
9
debromination reaction of the dibromo-sulfone 6 using
activated Zn-dust in a suitable high boiling point solvent.
This approach could allow the one-pot double Diels–Alder
reactions of 6, using temperature as the only chemocontrol
28% overall yield or in a one-step procedure using a
2
0
diazadiene-stabilised palladacyclopentadiene, in 82% yield.
These products can be oxidized quantitatively to yield 2,3,6,7-
tetrasubstituted naphthalene derivatives which are important
starting compounds for the preparation of thermally stable
polyimides but difficult to obtain by other synthetic
2
element. In addition to Ph O, triethylene glycol dimethyl ether
and DMSO, we also employed in this study 5-nonanone. That
was based on the fact that the 1,4-debromination reaction is
2
0,21
routes.
1
8
facilitated in ketone solvents like acetone. Initial experi-
In order to extend our methodology in one-pot, thermally
chemocontrolled, double Diels–Alder reactions utilising two
different dienophiles (Scheme 4), DMAD was used in the first
Diels–Alder reaction and N-methylmaleimide in the second,
under the optimum reaction conditions found (Table 1, entry
5). The Diels–Alder adduct 16 was isolated in 85% overall yield
and characterized by NMR spectroscopy, mass spectrometry
and by X-ray crystallography (Fig. 1). An elegant synthesis of
ments were performed at a 0.038 mmol scale of 6 (concentra-
2
1
tion 6 mg mL ), utilising an excess of DMAD and using
conventional heating at 65–70 uC (Table 1, entries 1–4).
Monitoring was performed by TLC to identify the formation
of either the diene-sulfone 7 or the first Diels–Alder adduct 11.
2
Of the solvents screened, Ph O (bp 259 uC), triethylene glycol
dimethyl ether (bp 216 uC) and DMSO (bp 189 uC) afforded
only decomposition material (Table 1, entries 1–3). In
2
2
similar Diels–Alder adducts was reported by Trost but
required several steps, catalysts and gave lower overall yields.
To reach our target for an elegant and practical method for
the [4 + 2] functionalisation of C60 and the subsequent [4 + 2]
derivatization in a one-pot manner, diene-sulfone 7 was firstly
5-nonanone (bp 187 uC), the starting material 6 was stable
for up to one week at 65–70 uC and a clear indication of the
product 11 formation was observed (Table 1, entry 4).
However, even in 5-nonanone, temperatures higher than 70
uC led to the exclusive formation of decomposition material
1
8
prepared following our procedure and subjected in a [4 + 2]
a
Table 1 Optimisation of the one-pot thermally chemocontrolled double Diels–Alder reactions with DMAD, starting from 6
Entry Conditions for 1,4-debromination/1st D–A
TLC result
dec.
Conditions for SO
2
extrusion/2nd D–A Yield of 12 (%)
1
2
3
4
5
Ph
2
O, 65–70 uC, up to 4 d
—
—
—
—
—
—
—
triethylene glycol dimethyl ether, 65-70 uC, up to 4 d dec.
DMSO, 65–70 uC, 1 h
5-nonanone, 65-70 uC, up to 1 week
5-nonanone, MW (250 W, 21 psi, 65 uC), 8 h
dec.
starting material + 11
11
—
b
c
d
170–180 uC, 30 min
83
a
Results are based on an average of two runs. The reactions were carried out at a 0.038 mmol scale of 6 (1 equiv) and at a concentration of 6
2
1
b
c
mg mL . Conditions: Zn-dust (2.3 equiv), DMAD (10 equiv). CEM Discover microwave reactor. Conventional heating. The reaction was
transferred in a 10 mL two-neck round-bottomed flask fitted with a magnetic stirrer, condenser and a thermometer. Extra 2 mL of
d
5
-nonanone were added. Isolated yield.
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energy of the thermal SO
2
extrusion presumably due to its
electronegative character. This is a major advantage since
sensitive functionalities can be tolerated in the second Diels–
Alder reaction of the sequence. Finally, the stability of
monoadduct 14 was confirmed experimentally by refluxing
its solution in o-DCB (180 uC) for 3-4 h with no indication of a
retro Diels–Alder reaction.
Conclusions
In summary, we have demonstrated a practical and efficient
method for thermally chemocontrolled double Diels–Alder
processes in a one-pot manner, starting from 3,4-bis(bromo-
methyl)-2,5-dihydrothiophene-1,1-dioxide (6). The 1,4-debro-
mination of 6 was achieved with Zn-dust, in 5-nonanone as the
solvent, under microwave conditions. The use of this high
boiling point solvent allowed all the steps (1,4-debromination/
Scheme 4 One-pot thermally chemocontrolled double Diels–Alder reactions of
7
with two different, Zn-compatible dienophiles.
cycloaddition reaction with C60 in toluene, at 45–50 uC
Scheme 5). Upon completion in 12 h, DMAD was added and
(
2
1st Diels–Alder/SO extrusion/2nd Diels–Alder) to occur in
the temperature was raised at 110 uC for 30 min. TLC analysis
of the crude reaction mixture revealed the clean formation of a
single C60 adduct which was purified by column chromato-
graphy (toluene–EtOAc = 20 : 1) followed by precipitation from
practically one-pot manner by only adjusting the reaction
temperature. Using this approach, tetramethyl 1,4,5,8-tetra-
hydro-2,3,6,7-naphthalenetetracarboxylate was synthesized in
a single step in 83% yield, utilising an excess of DMAD. This
method worked very efficiently when two different dienophiles
CHCl
ported the structure of monoadduct 14 which was isolated in
3% yield. In comparison, the traditional stepwise method for
3
–pentane. The spectroscopic data unambiguously sup-
(
DMAD and N-methylmaleimide) were utilized in the cycload-
dition steps to afford the corresponding Diels–Alder adduct in
5% yield. The construction of more complex polycyclic
5
the synthesis of monoadduct 14 starting from 6 proceeded in
two steps and 59% overall yield (Scheme 3).
8
compounds should become easily accessible by using this
simplified route.
An important aspect regarding monoadduct 17 (Scheme 5)
lies in the fact that the temperature required for the SO2
Following this strategy, an elegant and practical [4 + 2]
functionalisation/[4 + 2] derivatization of C60 process, in a one-
pot manner, was achieved. The reaction proceeded via the
formation of the new C66 dienic intermediate 3 which was
further derivatized via a Diels–Alder reaction with DMAD. An
extrusion was considerably lower (100–110 uC) than the usual
1
4
SO extrusion temperatures (170–180 uC). In order to confirm
2
this experimental observation we studied the thermal proper-
ties of monoadduct 17 by TGA and DSC measurements (see
ESI
3
). The obtained data were in full agreement with the
important finding was the considerably lowered SO extrusion
2
experimentally determined extrusion temperature and com-
pared to the ones determined for the corresponding 3-sulfo-
lenes 6 and 11, it was lowered by 70 uC. Obviously, the
fullerene moiety in 17 lowers considerably the transition state
temperature of 17 (100–110 uC) which was determined
experimentally and with the aid of TGA and DSC. A large
number of C60 derivatives should become easily available by
using dienophiles with a wide range of chemical functional-
ities but most importantly, this method could be applied in
the functionalisation/derivatization of other carbonaceous
materials such as carbon nanotubes or graphene.
Experimental
General experimental
All starting materials were purchased from commercial
sources and used without further purification. The solvents
were dried using appropriate standard procedures. Zinc was
2
3
activated according to a known procedure. Column chroma-
tography was carried out using Merck silica gel 60H (40–60
nm, 230–300 mesh). Thin-layer chromatography (TLC) was
carried out on aluminium plates coated with Merck HF254/366
silica gel. Visualisation was performed under a 254 nm
ultraviolet (UV) light source and/or by immersion in potassium
Scheme 5 One-pot thermally chemocontrolled strategy for [4 + 2] functiona-
lisation/[4 + 2] derivatization of C60
.
permanganate (KMnO
4
) or phosphomolybdic acid (PMA)
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1
13
solutions, followed by heating. H NMR and C NMR spectra
were recorded either on a Bruker Avance 300 (300 MHz) or on a
Bruker Avance III 500 Ultrashield Plus (500 MHz) spectro-
meter. Residual non-deuterated solvent was used as the
General procedure for thermal SO extrusion/[4 + 2]
cycloaddition/aromatization reaction illustrated by:
2
Dimethyl 4,5-di(bromomethyl)phthalate (10). In a dry 15 mL
two-neck round-bottomed flask fitted with a magnetic stirrer,
condenser and a thermometer, 3,4-bis(bromomethyl)-2,5-
dihydrothiophene-1,1-dioxide 6 (29.5 mg, 0.097 mmol) was
dissolved in diphenyl ether (6 mL) under an atmosphere of dry
nitrogen. Dimethyl acetylenedicarboxylate (138 mg, 119.3 mL,
1
internal standard for H NMR spectra and a carbon signal of
the solvent was used as the internal standard for C NMR
spectra. Chemical shifts (dH and d ) are quoted in parts per
million (ppm) downfield from tetramethylsilane (TMS). The
resonance multiplicity patterns are described as singlet (s),
broad singlet (br s), doublet (d), triplet (t), quartet (q), quintet
quin.), multiplet (m), or combinations of those. Coupling
constants (J) are quoted in hertz (Hz). Peak assignments were
aided by H- H COSY, H- C HMQC, DEPT-135 and/or DEPT-
0, whenever necessary. High resolution mass spectra were
recorded either on MALDI TOF Bruker Autoflex III
Smartbeam instrument using DCTB as the matrix or on a
LTQ Orbitrap XL spectrometer. Infrared (IR) spectra were
recorded on a Shimadzu FTIR-NIR Prestige-21 spectrometer
with a Pike Miracle Ge ATR accessory and bands are quoted in
cm . Differential scanning calorimetric (DSC) measurements
were performed on a DSC TA Q1000 apparatus using a heating
curve from 25 to 300 uC, under argon atmosphere with a
heating rate of 5 uC min . The samples (0.8–1.5 mg) were
measured in hermetically sealed aluminium pans.
Thermogravimetric analysis (TGA) measurements were per-
formed on a TGA TA Q500 analyzer under argon atmosphere
with about 10 mg of the samples at a heating rate of 10 uC
1
3
C
0.970 mmol) was then added and the temperature of the
resulting mixture was raised at 170–180 uC for 30 min. During
this time the consumption of the starting material was
monitored by TLC (hexane 100% then EtOAc–hexane = 5 : 4).
The reaction mixture was then allowed to cool at room
(
1
1
1
13
9
2
temperature and MnO (42.2 mg, 0.485 mmol) was added. The
a
mixture was heated at 80–90 uC for two more hours and then
was allowed to cool at room temperature. The crude mixture
was subjected to column chromatography on silica gel (hexane
1
00% then Et O–hexane = 1 : 2). Removal of the solvent under
2
2
1
reduced pressure afforded product 10 as a white solid (29.9
1
13
mg, 81%). The H- and C NMR resonances were in good
1
4b
agreement with the data reported in the literature.
2
1
General procedure for the one-pot thermally chemocontrolled
1
,4-debromination/[4 + 2] cycloaddition/SO extrusion/[4 + 2]
2
cycloaddition reaction of 6 with Zn-compatible dienophiles
illustrated by:
2
1
Tetramethyl 1,4,5,8-tetrahydro-2,3,6,7-naphthalenetetracar-
boxylate (12). In a CEM Discover microwave sealed tube fitted
with a magnetic stirrer, 3,4-bis(bromomethyl)-2,5-dihydrothio-
phene-1,1-dioxide 6 (11.6 mg, 0.038 mmol) was dissolved in
min from 25 to 400 uC, using ceramic pans. A CEM Discover
Microwave Reactor was used for microwave experiments.
Melting points (mp) were determined on a Stuart Scientific
SMP10 apparatus, and were uncorrected.
5
-nonanone (2 mL) under an atmosphere of dry nitrogen.
2
General procedure for thermal SO extrusion/[4 + 2]
cycloaddition reaction illustrated by:
Activated Zn-dust (19.9 mg, 0.304 mmol) and dimethyl
acetylenedicarboxylate (54.0 mg, 46.7 mL, 0.380 mmol) were
then added and the resulting mixture was heated at 65 uC (250
W, 21 PSI) for 8 h. During this time the consumption of the
Dimethyl 4,5-di(bromomethyl)-1,4-cyclohexadiene-1,2-dicar-
boxylate (9). In a dry 15 mL two-neck round-bottomed flask
fitted with a magnetic stirrer, condenser and a thermometer,
2
starting material was monitored by TLC (2 times with Et O–
hexane = 1 : 2 then EtOAc–hexane = 5 : 4). The reaction
mixture was then transferred in a dry 10 mL two-neck round-
bottomed flask fitted with a magnetic stirrer, condenser and a
thermometer and extra 2 mL of 5-nonanone were added. The
temperature of the resulting mixture was raised at 170–180 uC
for 30 min and the reaction was monitored by TLC (2 times
3
,4-bis(bromomethyl)-2,5-dihydrothiophene-1,1-dioxide
6
(31.5 mg, 0.104 mmol) was dissolved in diphenyl ether (6
mL) under an atmosphere of dry nitrogen. Dimethyl acetyle-
nedicarboxylate (147.3 mg, 127.4 mL, 1.04 mmol) was then
added and the temperature of the resulting mixture was raised
at 170–180 uC for 30 min. During this time the consumption of
the starting material was monitored by TLC (hexane 100%
then EtOAc–hexane = 5 : 4). The reaction mixture was then
allowed to cool at room temperature and the crude mixture
was subjected to column chromatography on silica gel (hexane
with Et O–hexane = 1 : 2 then EtOAc–hexane = 2 : 3). The
2
reaction mixture was then allowed to cool at room temperature
and the crude mixture was subjected to column chromato-
graphy on silica gel (Et O–hexane = 1 : 2 then EtOAc–hexane =
2
2
: 3). Removal of the solvent under reduced pressure afforded
2
100% then Et O–hexane = 1 : 2). Removal of the solvent under
product 12 as a white solid slightly contaminated with the
aromatized form 13 (11.5 mg, 83%).
Alternative method for the preparation of 12 (from 11).
reduced pressure afforded product 9 as a white solid
contaminated with the aromatized form 10 (9 : 10 = 20 : 1 by
1
H NMR integration) (27.4 mg, 83%). R 0.28 (Et O–hexane =
f
2
1
9
1
: 2, UV or KMnO ). mp 72–73 uC (from hexane) (lit., 75–76
uC). IR, nmax (ATR)/cm : 2973, 2962, 2920, 1731, 1647, 1297,
Following the general procedure provided for 9 (thermal SO
extrusion/[4 + 2] cycloaddition), using dimethyl 1,3,4,7-tetra-
2
4
2
1
1
18
1
(
CO
260, 1238, 1210, 1150, 1142, 1039, 938, 911, 855, 813. H NMR
300 MHz, CDCl ): d 4.03 (br s, 2 x CH , 4H), 3.80 (br s, 2 x
, 6H), 3.19 (br s, 2 x CH
): d 167.45 (CLO), 131.52 (.CL), 129.55 (.CL), 52.46
), 31.46 (CH ), 29.27 (CH ). HRMS (APCI+): calculated
for C12 [M 2 H] requires 378.9175; found: 378.9173.
hydrobenzo[c]thiophene-5,6-dicarboxylate-2,2-dioxide
11
(30.6 mg, 0.107 mmol) and dimethyl acetylenedicarboxylate
(151.9 mg, 131.4 mL, 1.07 mmol) afforded product 12 (22.8 mg,
87%) as a white solid, after purification by column chromato-
graphy on silica gel (hexane 100% then EtOAc–hexane = 2 : 3).
3
H
2
1
3
2
CH
3
2
, 4H). C NMR (125 MHz,
CDCl
OCH
3
C
(
3
2
2
+
H
13Br
2
O
4
f 4
R 0.34 (EtOAc–hexane = 2 : 3, UV or KMnO ). mp 186–187 uC
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1
9
21
(
from EtOH) (lit., 191–192 uC). IR, nmax (ATR)/cm : 2953,
Precipitation from CHCl
3
–pentane afforded product 14 as a
1
7
1
1
732, 1707, 1659, 1433, 1265, 1198, 1151, 1061, 1012, 947, 905,
brown solid (34.6 mg, 53%).
1
85. H NMR (500 MHz, CDCl ): d 3.79 (br s, 4 x CO CH ,
Alternative method for the preparation of 14. Following the
general procedure provided for 9, using dimethyl 1,3,4,7-
tetrahydrobenzo[c]thiophene-5,6-dicarboxylate-2,2-dioxide 11
(16.2 mg, 0.057 mmol) and C60 (48.9 mg, 0.068 mmol) in
o-dichlorobenzene (40 mL) afforded product 14 (31.5 mg, 59%)
as a brown solid, isolated after column chromatography on
3
H
2
3
1
3
2H), 2.92 (br s, 4 x CH
2 3 C
, 8H). C NMR (125 MHz, CDCl ): d
67.98 (CLO), 132.22 (.CL), 120.44 (.CL), 52.34 (OCH ), 31.64
3
+
(CH
2 21 8
). HRMS (APCI+): calculated for C18H O [M + H]
requires 365.1231; found: 365.1232.
Tetramethyl naphthalene-2,3,6,7-tetracarboxylate (13).
Following the general procedure provided for 10 (thermal
silica gel (toluene–EtOAc = 20 : 1) and precipitation from
1
CHCl
3
–pentane. R
f
0.33 (toluene–EtOAc = 20 : 1). H NMR (500
2
SO extrusion/[4 + 2] cycloaddition/aromatization), using
MHz, CS /CDCl , 1 : 1): d 3.94 (br s, 2 x CH , 4H), 3.77 (br s, 2
dimethyl 1,3,4,7-tetrahydrobenzo[c]thiophene-5,6-dicarboxy-
late-2,2-dioxide 11 (28.9 mg, 0.101 mmol), dimethyl acetylene-
dicarboxylate (143.4 mg, 124.1 mL, 1.01 mmol) and MnO (87.8
2
2
3
H
2
1
3
x CO CH , 6H), 3.51 (br s, 2 x CH , 4H). C NMR (125 MHz,
2
3
2
CS
2
/CDCl
3
, 1 : 1): d
C
167.86 (CLO), 156.15, 147.59, 146.46,
1
1
46.19, 145.74, 145.42, 145.23, 144.62, 143.08, 142.55, 142.28,
41.99, 141.57, 140.14, 135.63, 132.84, 129.63, 65.74 (sp C of
mg, 0.101 mmol) afforded product 13 (31.3 mg, 86%) as a
3
white solid, isolated after column chromatography on silica
1
13
C ), 52.26 (OCH ), 43.65 (CH ), 32.70 (CH ). HRMS (MALDI
60 3 2 2
gel (hexane 100% then EtOAc–hexane = 2 : 3). The H- and
C
14 4
TOF, negative mode, DCTB): calculated for C72H O [M 2
NMR resonances were in good agreement with the data
2
2
0
4H] requires 938.0574; found: 938.0575.
reported in the literature.
Dimethyl 2-methyl-1,3-dioxo-2,3,3a,4,5,8,9,9a-octahydro-
1H-benzo[f]isoindole-6,7-dicarboxylate (16). Following the gen-
eral procedure provided for 12 (1,4-debromination/[4 + 2]
cycloaddition/SO extrusion/[4 + 2] cycloaddition), using 3,4-
bis(bromomethyl)-2,5-dihydrothiophene-1,1-dioxide (10.7
mg, 0.035 mmol), activated Zn-dust (18.4 mg, 0.282 mmol),
dimethyl acetylenedicarboxylate (5 mg, 4.3 mL, 0.035 mmol) as
the first dienophile and N-methylmaleimide (4.7 mg, 0.042
mmol) as the second dienophile afforded product 16 (10 mg,
Acknowledgements
2
This work was financially supported by the Cyprus Research
Promotion Foundation (Grant NEKYP/0308/02). We also thank
Dr P. A. Koutentis (Department of Chemistry, University of
Cyprus) for providing access to the TGA, DSC instruments and
the microwave reactor.
6
85%) as a white solid, isolated after column chromatography
on silica gel (hexane 100% then EtOAc–hexane = 5 : 4). R 0.28
f
(
EtOAc–hexane = 5 : 4, UV or KMnO
4
). mp 122–123 uC (dec.).
Notes and references
2
1
IR, nmax (ATR)/cm : 2953, 1734, 1713, 1693, 1435, 1427, 1383,
1
(a) For examples of C60 derivatives in materials science, see:
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1
307, 1277, 1259, 1148, 1142, 1065, 1042, 978, 953, 806.
NMR (500 MHz, CDCl ): d 3.75 (br s, 2 x CO CH , 6H), 3.11–
.10 (m, 2 x CH, 2H), 3.03–2.87 (m, 7H), 2.44 (d, J = 15.5 Hz,
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