Piperazine additions to C60 - A facile approach to fullerene substitution

Article abstract of DOI:10.1039/b413173h

A range of fullerene monoadducts can be generated via the photochemical reaction of piperazine derivatives with C₆₀. Addend functionality can also be efficiently incorporated by transformation of the hydroxyl-substituted adduct prepared in this fashion. Reaction yields and process simplicity compete with current standard procedures for fullerene mono-functionalisation. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b413173h

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A R T I C L E
Piperazine additions to C60—a facile approach to fullerene
substitution
Craig P. Butts* and Mikael D. S. Jazdzyk
School of Chemistry, University of Exeter, Exeter, United Kingdom.
E-mail: c.p.butts@ex.ac.uk; Fax: +44 1392 263434; Tel: +44 1392 263455
Received 27th August 2004, Accepted 19th January 2005
First published as an Advance Article on the web 22nd February 2005
A range of fullerene monoadducts can be generated via the photochemical reaction of piperazine derivatives with C60.
Addend functionality can also be efficiently incorporated by transformation of the hydroxyl-substituted adduct
prepared in this fashion. Reaction yields and process simplicity compete with current standard procedures for
fullerene mono-functionalisation.
Introduction
The numerous chemical reactions of fullerenes1 have been
well documented over the last decade. The Bingel addition–
elimination of halomalonates, Prato’s dipolarcycloadditions of
azomethine ylids and Diels–Alder reactions of quinodimethanes
are probably the most general, substrate tolerant methods for
addition to C60 and find numerous applications including ma-
terials synthesis.2 By comparison, most other addition methods
give low yields and are often highly substrate specific.
We have been interested in developing the reaction of C60
with amines into a useful synthetic technique for monoaddition
to fullerenes. The reactions of C60 with amines3 (Scheme 1)
Scheme 2 Reaction of a diamine (piperazine) with C60.
and diamines4 (Scheme 2) have been employed in a small
number of studies. However, in a synthetic sense, these have been
diamine reactions with C60, these procedures have been shown
neither particularly facile nor selective. Indeed the predominant
to form only 1,2-dehydroaminylated adducts (Scheme 2).4
product formed is highly dependent on the reaction conditions
In all cases, the reactions of amines (and diamines) with C60
are believed to proceed via electron transfer from the amine
and reagents chosen. Reactions of secondary amines with C60
can give 1,2-hydroamination and 1,4-hydroamination products,5
donor to the readily reduced fullerene.3 These processes are
or 1,4-dehydroamination adducts,6 while the photochemical
promoted by UV irradiation as the photochemical reaction
reaction of a tertiary amine gives the corresponding pyrollidines
(Scheme 1). To exacerbate these difficulties, exposure of these
proceeds via photon absorption to give 3C60* (via 1C60*), which
readily undergoes the single electron transfer with the amine
reaction mixtures to oxygen can give rise to alternative products,
donor to give the radical anion–cation pair. Radical–radical
such as adduct-oxides7 and fullerene dimers.6 In the case of
coupling and proton transfer within this radical anion–cation
pair generates the hydroaminated adducts but the latter stages
of the dehydrogenative diamination mechanism are not clear.
The low yields of monoadduct and variety of regiochemical
outcomes from C60–amine reactions has effectively prevented the
development of any synthetic utility in this method of fullerene
adduct generation. Prior to our work in the field,8,9 the only
reported yield above 25% for a diamine–C60 monoadduct was
50%,4 for the preparation of monoadduct 2a◦from the reaction
of 8 eq. of piperazine with C60 for 3 d at 80 C. A more rapid
photochemical procedure (KMnO4 filter, 505 nm cutoff) for the
preparation of 2a was subsequently reported by Sun et al.10
which required only 70 min at room temperature, but gave a
relatively low yield of monoadduct 2a (<25%) and still employed
a significant excess (7 eq.) of the diamine reagent. Acyclic
diamines required larger excesses of amine and gave much lower
yields than piperazine under all reaction conditions. Recently
we have reported an efficient preparation of the piperazine–C60
adduct 2a in 73% yield8 although application of this method to
acyclic diamines has been frustratingly unsuccessful.
The limited substrate flexibility can be addressed by preparing
a fullerene adduct which contains a reactive functional group.
This adduct can then be transformed, via its reactive functional
group, into a range of desired products using conventional syn-
thetic methods—the concept of the fullerene ‘synthon’. These
materials should be more prone to synthetic manipulation than
Scheme 1 Typical reactions of C60 with amines.
T h i s j o u r n a l i s
the parent fullerenes and, as fullerene adducts are more soluble
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6
1 2 0 9
©

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than their parent compounds, these ‘synthons’ possess a much
broader synthetic scope. Kordatos et al. recently outlined such
transformations of fulleropyrrolidines containing an N-Boc
protected primary amine (Scheme 3).11 Reaction of the amine
group gave access to a variety of fullerene-derived compounds.
This general approach to fullerene functionalisation has also
previously been reported by a few others, notably the early use of
hydroxyl-substituted quindimethano-derivatives by Zhang and
Foote12 and later Nakamura et al.13
Hirsch3 suggested that the presence of dioxygen in these mix-
tures allowed radical mechanisms to proceed, hence promoting
N,Nꢀ-dehydroaddition products rather than hydroamination.
Bernstein and Foote15 also implicated singlet oxygen in the
mechanism of the photochemical reaction of C60 with a tertiary
propargylamine since addition of the competitive quencher
DABCO was observed to reduce the yield of addition products.
Similarly, thermal generation of singlet oxygen in the presence
of C60 and the tertiary amine gave rise to the expected addition
products. These same reactions performed under inert atmo-
spheres were reported to give reduced yields. This contrasts with
the reports by Kampe et al.4 in which highly efficient formation
of the C60–piperazine monoadduct 2a could be achieved under
a nitrogen atmosphere.
In our hands, it was found that a highly oxygenated atmo-
sphere was detrimental to the photochemical procedure, leading
to a rapid colour change from the typical purple C60–toluene
solution to brown. The UV-vis absorption spectrum of the
resulting mixture did not correspond to that of a typical 6,6-
monoadduct (no peak at 440 nm was observed) and only a very
small amount of adduct could be isolated. The majority of the
fullerene-based material formed an insoluble precipitate during
photolysis and workup, which could not be analysed. This is
consistent with the photochemical formation of fullerene dimers
in the presence of oxygen.16 Exclusion of oxygen by N2 purging
and/or freeze-thaw cycling of all solutions prior to irradiation
and conducting all manipulations and irradiation under an inert
atmosphere, all gave the expected result—high reaction yields
of the monoadduct 2a (typically >50% depending on reaction
stoichiometry) and no apparent precipitation.
Scheme 3 Generic transformations of the fullerene ‘synthons’ of
Kordatos et al.11
This study describes the optimisation of piperazine–C60
photochemical reaction conditions, the generation, structural
characterisation and some illustrative examples of reactions of
substituted piperazine–C60 monoadducts.
Solvent. Changes in reaction solvent were examined, in the
main to ascertain whether higher concentrations of C60 could
be employed in these photochemical procedures. The limiting
concentration of C60 in toluene is around 2.8 mg ml−1,14 however
preparing solutions at even these low concentrations requires
extended sonication of solid C60 in toluene. Irradiation of
chlorobenzene or dichlorobenzene solutions of C60 (limiting
solubilities 7.0 mg ml−1 and 27.0 mg ml−1, respectively)14 and
piperazine gave rise to a rapid reaction of the C60 as assessed
by monitoring the UV-vis spectrum of the mixture. However,
no marked increase in absorbance at around 440 nm was
observed, suggesting a lack of monoadduct formation. Indeed
a 1H NMR spectrum of the product mixture showed a complex
composition, including multiple aromatic products and attempts
to separate or identify any C60-containing materials were un-
successful. A control experiment in chlorobenzene, conducted
without the piperazine, gave a similar result indicating that
the observed reaction is independent of the diamine-addition
mechanism. Chlorobenzene is known17 to dissociate under
irradiation at 266 nm into chlorine and phenyl radicals which will
react very rapidly with C60. The high concentration of radicals
likely to be formed under the irradiation of a chlorobenzene–
C60 mixture would give rise to a complex mixture of aromatic,
chlorinated and C60-polyaddition products, as observed. It was
also found that the addition of CS2, another reasonable solvent
for C60 (7.9 mg ml−1),14 to the toluene solutions severely inhibited
the solubility of the piperazine reagent. Hence toluene remains
the solvent of choice for these procedures.
Results and discussion
Reaction optimisation
Irradiation wavelength. Conditions for the photochemical
reaction were optimised for the preparation of piperazine–C60
adduct 2a, using an unfiltered medium pressure mercury lamp
in a quartz water jacket, generally immersed in the reaction
solution. While small variations in temperature should not play
a significant role in the photochemical addition reaction, the
reaction mixture was maintained at 23 ◦C by immersion of
the photolysis vessel in a thermostatic water bath. Reactions
were monitored by UV-vis spectroscopy performed on aliquots
removed from the reaction mixture at appropriate intervals and
all yields discussed are after isolation.
It appears that the wavelength of radiation incident on the
sample is critical to the success of photochemical additions of
piperazines to C60. The irradiation of toluene solutions of C60
(1 mg ml−1) and piperazine (2 eq.) at 265 and 366 nm respectively
was monitored by UV-vis spectroscopy on regular aliquots. A
steady increase in the absorbance of the aliquots at 440 nm
was observed with time in both cases. This absorbance change is
indicative of 1,2-adduct formation across a double bond between
two six-membered rings of the fullerene14 (a 6,6-monoadduct) in
both experiments. However, the absorbance increase at 439 nm
was approximately 4 times faster in the UV-vis spectrum of
solutions irradiated at 265 nm. Similarly, unfiltered irradiation
of a toluene solution of C60 (1 mg ml−1) and piperazine (1 eq.)
contained in a pyrex vessel (ca. 50% transmission at 310 nm) gave
essentially no conversion under conditions where significant
monoadduct formation was observed in reactions contained in
quartz vessels. This suggests that the shorter of the principal
emission wavelengths of a mercury lamp (254, 265, 297, 313 and
366 nm) are the most effective in promoting diamine addition
to C60. Hence all reactions were performed using unfiltered
radiation from a medium-pressure mercury lamp through a
quartz water jacket.
Stoicheiometry and time. The ratio of piperazine : C60
required for efficient photochemical reaction was examined. In
previous thermal and photochemical studies4,10 a large excess of
diamine has been used and low yields obtained. We assumed
that these low yields were due to significant formation of bis-
addition products at extended reaction times. Table 1 shows
representative yield data for the generation of monoadduct 1 by
reaction of piperazine with C60 (1 mg ml−1). It is clear that near-
stoichiometric quantities of diamine reagent are preferable to
maximise the yield of monoadduct. Reaction times significantly
above 18 h were found to reduce yields of monoadduct 1 slightly.
Oxygen. The effect of molecular oxygen on the photo-
chemical reactions of amines and C60 is somewhat unclear.
1 2 1 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6

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Table 1 Optimisation of diamine–C60 ratios and reaction times for the
a fullerene ‘synthon’ for further transformations. Scheme 4
outlines the results of simple transformations of adduct 2f via
the nucleophilic hydroxyl group. While adduct 2f is significantly
more soluble than C60 in standard organic solvents, all of the re-
actions were performed in 1 : 1 dichloromethane–chlorobenzene
solvent mixtures to ensure rapid dissolution.
Esterification of adduct 2f with acroyl chloride or para-
bromobenzoyl chloride gave the corresponding esters 2h and 2i
in 71 and 62% yields respectively following column chromatog-
raphy. Analogous reactions employing a carboxylic acid reagent
and thionyl chloride to prepare the corresponding acid chloride
in situ gave comparable results. Incorporation of the acid moiety
was confirmed by integration of the1H NMR spectra of the
isolated adducts, 13C NMR spectroscopy and observation of the
parent ions at 889 and 1017 a.m.u. respectively.
The reaction of adduct 2f with t-butyldimethylsilyl (TBDMS)
chloride at room temperature successfully generated the corre-
sponding silyl ether 2j in 67% yield. Incorporation of the silyl
moiety was confirmed by the presence and correct integration
of the methyl and t-butyl resonances in the 1H NMR spectrum
of adduct 2j and the observed parent ion at 949 a.m.u. As
mentioned above, adduct 2j could not be prepared directly by
addition of the silyl ether of 1f to C60, due to the instability
of the substituted piperazine under the photochemical reaction
conditions.
Sulfonic acid esters of adduct 2f were prepared by mixing
adduct 2f with p-toluenesulfonyl chloride or methanesulfonyl
chloride for 48 h at room temperature. The sulfonyl esters 2k
and 2l were isolated in 54 and 46% yields respectively after
chromatography. The incorporation of the sulfonyl group in
both adducts 2k and 2l was confirmed by integration of the 1H
NMR spectra and observation of the parent ions at 913 and 989
a.m.u. respectively. The insolubility of the mesylate adduct in
standard NMR solvents (including CS2 admixtures) prevented
a reasonable 13C NMR spectrum from being obtained.
photochemical addition of piperazine to C60 (80 mg) in toluene (80 ml)
Entry
Ratio of piperazine : C60
Irradiation time/h
Yield (%)
1
2
3
4
5
6
20 : 1
5 : 1
3 : 1
2 : 1
1 : 1
1 : 1
0.25
0.5
2
2
7
32
37
40
40
50
73
18
Synthetic utility
Photochemical reactions of 2-substituted piperazine derivatives
with C60. We have previously reported9 that the photochemical
reactions of 2-substituted piperazines with C60 are similarly facile
under these conditions. Yields and conditions for successful
monoadditions to generate 2-substituted adducts 2a–g are
shown in Table 2. The substituted piperazines were either
purchased or prepared by modifications of the methods of
Rondu et al.18 and Bihan et al.19 In all cases, it was found that
the photochemical monoaddition of 2-substituted piperazines to
C60 proceeded significantly more slowly than that of the parent
piperazine. The consequent need for extended reaction times led
to lower yields, however, increasing the diamine : C60 ratio to
3 : 1 and irradiating for around 64 h was found to offset this
sufficiently such that yields approaching 45% could be achieved
reproducibly for 2-methylpiperazine. The especially low yield
achieved for the primary amide adduct 2d appears to be due
to the low solubility of the piperazine reagent in the toluene
solvent, even at extended reaction times.
t
In some cases, (R = CO2Et, OSiMe2 Bu) no monoadduct
could be isolated from the reaction mixture, despite the observa-
tion of the expected purple to brown colour change over a period
of time. In both cases, the excess piperazine reagents could not
be re-isolated from the reaction mixtures and it appears that the
diamine reagents are not stable under the reaction conditions.
Presumably coupling of the piperazine decomposition products
with C60 gives rise to the observed colour change. As irradiation
of the substituted piperazine in the absence of C60 does not
lead to decomposition of the heterocycle, it seems likely that
the intermediate radical cation of these piperazine derivatives is
unstable and decomposes prior to radical recombination with
the fullerene radical anion.
The sulfonyl esters 2k and 2l are themselves potential elec-
trophilic fullerene synthons. Indeed, the reaction of adduct 2l
with sodium iodide in 2 : 3 acetone–chlorobenzene, furnished
the corresponding iodomethyl adduct 2m in a 43% yield
following column chromatography. Again, this material proved
too insoluble for characterisation by 13C NMR spectroscopy,
1
but the H NMR spectrum of 2m showed the lack of a methyl
resonance in the product. The parent ion was also observed at
945 a.m.u.
Somewhat surprisingly, attempts to generate alkyl, allyl or
aryl ethers of adduct 2f by modified Williamson ether synthe-
sis (in ether–chlorobenzene) or Mitsunobu-type reactions (in
toluene) were unsuccessful. In the former case, no reaction
Transformations of adduct 2f. The hydroxymethyl adduct
2f, which is readily prepared in a 43% yield (Table 2) by the
photochemical addition procedure, can also be employed as
Table 2 Yields of monoadducts 2a–g from the photochemical reaction of 3 eq. piperazines 1a–g with C60 (80 mg) in toluene (80 ml)
Entry
Addend
Adduct
R
Rꢀ
time/h
Yield (%)
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
H
CH3
CH2OC6H13
CONH2
CONHC3H7
CH2OH
CH3
H
H
H
H
H
H
CH3
18
64
64
64
64
64
64
73a
41
10
6
27
43
20b
1g
2g
a Reaction employed 1 equivalent of piperazine 1a; b Reaction employed 5 equivalents of 1g.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6
1 2 1 1

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Scheme 4 Preparation and reactions of fullerene adduct 2f; (a) RCOCl, NEt3, DMAP, 1 : 1 CH2Cl2–chlorobenzene; (b) tbutyldimethylsilyl chloride,
imidazole, 1 : 1 CH2Cl2–chlorobenzene; (c) RSO2Cl, triethylamine, 1 : 1 CH2Cl2–chlorobenzene; (d) 2l, NaI, 2 : 3 acetone–chlorobenzene.
whatsoever could be observed and the starting material 2f was
re-isolated. In the latter case, all of the initial adduct 2f was
consumed, but no identifiable product could be isolated. It
seems likely that monoadduct 2f reacts with the intermediate
1,3-dipole generated by the reaction of triphenylphosphine with
diisopropylazo(dicarboxylate) (DIAD). Similarly, attempts to
oxidise the primary hydroxyl group to an aldehyde, using the
Dess–Martin periodinane or Swern conditions were ineffective.
Direct halogenation of 2f by reaction with triphenylphosphine
and carbon tetrahalides was also unsuccessful. In all instances
control reactions with a model compound, N,Nꢀ-dibenzyl-2-
(hydroxymethyl)piperazine, were successful in the appropriate
solvent.
suggest that there is little steric difference between the two
configurations.
The configuration of adducts 2h and 2i, prepared by trans-
formation of hydroxymethyl adduct 2f, can also be confirmed
by COSY and NOE NMR experiments. In both cases an NOE
is observed between the C2ꢀ-methylene protons and the H6ꢀ-exo
proton confirming their 1,3-diaxial arrangement. The analogous
NOE is not observed for the precursor 2f. However, given the
configuration of 2h and 2i it seems clear that the hydroxymethyl
group of adduct 2f must indeed occupy an exo position, which
is retained by its derivatives. Extension of this suggests that
adducts 2j–m must also all be exo configured.
The configuration of all other 2-substituted adducts in this
report could not be unequivocally confirmed as NOE enhance-
ments were not observed between resonances for protons on
the C2ꢀ-substituent (where present) and a C6ꢀ-proton in these
cases. However, comparison of the detailed assignments of the
1H NMR spectra of adducts with known configurations (2b
and 2f–m) with amide adducts 2d and 2e shows a significant
deshielding of the C3ꢀ-exo protons in the latter instances. This
can be rationalised by the through-space effect of the C2ꢀ-
carbonyl group—which would require the assignment of the
C2ꢀ-substitution as exo once again. Finally, we have previously
noted8 that the 1H NMR resonances of exo-protons in the
fully assigned adducts 2a and 2bwere consistently upfield of the
analogous endo-protons. The assignment of the 1HNMRspectra
of the remaining adducts 2c–m, assuming exo configurations of
the C2ꢀ-substituent, is entirely consistent with this and at this
stage we are confident that all C2ꢀ-substituted piperazine-C60
adducts can be assumed to be exo configured.
Configuration of 2-substituted adducts
The structure of the adduct 2a was confirmed by X-ray
crystallography20 as the 1,2-dihydrofullerene with the piperazine
adopting a ‘boat’ configuration. The introduction of a sub-
stituent on the piperazine ring both decreases the symmetry
of the resultant adduct and allows two possible configurations
in the resultant monoadduct, exo or endo (Fig. 1). We have
previously reported that the reaction of 2-methylpiperazine with
8
C60 results in only a single configuration in the monoadduct
2b, in which the methyl-substituent was found to be exo with
respect to the fullerene substituent. This was established by the
observation of a small NOE between the C2ꢀ-methyl resonance
and a C6ꢀ-proton resonance, which could only arise if both
groups occupy exo positions on the piperazine ring. The reason
for this preferred arrangement is presumably thermodynamic
in origin, although semi-empirical calculations (AM1) on both
configurations of 2b and the corresponding C2ꢀ-ethyl analogue
Conclusions
The photochemical reaction of piperazines with C60 is an
effective method for generating generic fullerene monoadducts.
Further transformations of the hydroxyl substituent in adduct
2f demonstrate the facility with which a broad range of fullerene
adducts can be readily prepared. In contrast to the substrate-
dependent fullerene addition reactions, the success of these latter
transformations is relatively independent of the nature of the
piperazine substituents. The yields and facility of the generation
Fig. 1 Possible addend configurations in adducts 2.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6
1 2 1 2

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of adducts of type 2 compare favourably with current standard
methods for fullerene functionalisation.
Piperazine-2-carboxylic acid amide (1d). A solution of 1,4-
dibenzylpiperazine-2-carboxylic acid amide (1 g, 2.8 mmol, see
below for preparation) in ethanol (10 mL) was treated with 10%
Pd/C under an H2 atmosphere overnight at room temperature.
The mixture was filtered through celite before removing the
solvent in vacuo, to give 350 mg (95%) of the title compound as
a white powder. The materi◦al was used in the next step without
Experimental
General notes
Photochemical experiments were conducted using an unfiltered
medium pressure mercury lamp surrounded by a quartz water
jacket, which was immersed in the reaction solution. All photo-
chemical reaction solutions and reagents were purged extensively
with nitrogen immediately before photolysis. Piperazine 1a
(Lancaster Chemicals), 2-methylpiperazine 1b (Avocado Chem-
icals), trans-2,5-dimethylpiperazine 1g (Avocado Chemicals)
were purified by sublimation prior to use. MALDI mass spectra
were obtained with a Bruker Reflex III MALDI-TOF Mass
Spectrometer. Nuclear Magnetic Resonance spectroscopy was
performed on a Brucker DRX400 or a Bruker ACF-300. Semi-
empirical calculations (AM1) were performed using Chem3D
software version 5.0 (CambridgeSoft).
1
purification. m.p. 144–145 C; H NMR (CDCl3, 300 MHz) d
2.66–2.92 (5H, m), 3.10 (1H, dd, J 3.4 Hz, 12.2 Hz), 3.28 (1H,
dd, J 3.5 Hz, 12.2 Hz), 5.47 (1H, br), 6.84 (1H, br); 13C NMR
(CDCl3, 100 MHz) d 45.69, 46.72, 49.46, 59.58, 175.34; m/z
130.0983 (expected 130.0980).
1,4-Dibenzylpiperazine-2-carboxylic acid amide. Prepared
according to the procedure used by Rondu et al.;18 3 g
of 2,3-dibromo propionamide (12.9 mmol) was added drop-
◦
wise to a hot (80 C) toluene solution (75 ml) of N,Nꢀ-
dibenzylethylenediamine 2.98 g (12.4 mmol) and 4.24 ml of
triethylamine. The reaction mixture was refluxed for 48 h and
then cooled. The crude mixture was washed with aqueous
sodium hydrogen carbonate (2 × 50 ml) and brine (1 ×
50 ml). The organic layer was dried over MgSO4 and the
solvent was removed in vacuo to give a white powder purified
General procedure for photochemical addition of piperazines
to C60
1
by recrystallisation (dichloromethane–ether) 2.83 g (74%). H
A toluene solution (ca. 5 ml) of the diamine (ca. 0.33 mmol)
was added to a toluene solution (total volume 80 ml) of C60
(80 mg, 0.11 mmol). Following nitrogen-purging, the solution
was irradiated for the appropriate period. The resulting product
mixture was separated by flash silica column chromatography.
C60 was eluted with a concentration gradient of hexane–toluene
before the monoadducts were eluted with toluene–methanol
(99 : 1). Elution with methanol gave no further products.
Products were isolated as brown powders after removal of
solvent in vacuo.
NMR (CDCl3, 300 MHz) d 2.25–2.42 (3H, m), 2.53–2.58 (1H,
m), 2.73–2.78 (1H, m), 2.88 (1H, dd, J 2.0 Hz, 11.0 Hz), 3.14
(1H, dd, J 3.4 Hz, 7.7 Hz), 3.38–3.52 (3H, m), 3.81 (1H, d, J
13.6 Hz), 7.26–7.34 (10H, m); 13C NMR (CDCl3, 100 MHz) d
49.73, 52.86, 56.09, 60.43, 63.18, 66.13, 174.80; m/z 310.1910
(expected 310.1919). Anal. calcd. for C22H29N3O:C, 73.81; H,
8.36; N, 12.91%. Found: C, 73.63; H, 7.77; N, 13.63%.
Piperazine-2-carboxylic acid propylamide (1e). A solution
of 1,4-dibenzylpiperazine-2-carboxylic acid propylamide (1 g,
2.8 mmol, see below for preparation) in ethanol (10 mL) was
treated with 10% Pd/C under an H2 atmosphere overnight at
room temperature. The mixture was filtered through celite before
removing the solvent in vacuo, to give 469 mg (96%) of the title
compound as a white powder. The material was used in the next
2-(Hexoxymethyl)piperazine (1c).
A
solution of 1,4-
dibenzyl-2-hexoxymethylpiperazine (1 g, 2.8 mmol, see below
for preparation) in ethanol (10 mL) was treated with 10% Pd/C
under an H2 atmosphere overnight at room temperature. The
mixture was filtered through celite before removing the solvent
in vacuo, to give 480 mg (91%) of the title compound as a waxy
white solid. The material was used in the next step without
◦
1
step without purification. m.p. 144–145 C; H NMR (CDCl3,
300 MHz) d 0.90 (3H, t, J 7.5 Hz), 1.50 (2H, sextuplet, J 7.1 Hz),
2.67–2.94 (5H, m), 3.14–3.22 (3H, m), 3.30 (1H, dd, J 3.4 Hz, 8.5
Hz); 13C NMR (CDCl3, 100 MHz) d 11.80, 23.22, 41.01, 45.75,
46.66, 49.73, 59.76, 172.51; m/z 172.1440 (expected 172.1450).
1
purification. H NMR (CDCl3, 300 MHz) d 0.87 (3H, t, J 6.9
Hz), 1.20–1.34 (6H, m), 1.53 (2H, p, J 6.6 Hz), 2.61 (1H, dd, J
1.3 Hz, 11.2 Hz), 2.84 (1H, m), 3.01–3.16 (5H, m), 3.28 (1H, dd,
J 2.2 Hz, 7.0 Hz), 3.35–3.43 (3H, m); 13C NMR (CDCl3, 100
MHz) d 14.47, 23.05, 26.15, 29.90, 31.99, 44.85, 45.49, 47.55,
54.39, 72.08, 72.48; m/z 201.1954 (expected 201.1967).
1,4-Dibenzylpiperazine-2-carboxylic acid propylamide. Pre-
pared according to the procedure used by Bihan et al.;19 0.65 ml
of n-propylamine (7.8 mmol) in toluene (10 ml) was added
dropwise to a stirred and cooled solution of 7.8 ml of Al(CH3)3
1,4-Dibenzyl-2-hexoxymethylpiperazine. To a suspension of
sodium hydride (134 mg, 1.8 mmol) in ether at 0 ◦C was
added, dropwise, a solution of 1-4-dibenzyl-2-(hydroxymethyl)
piperazine (0.5 g, 1.6 mmol, see below for preparation) in ether
(20 ml). The crude mixture was stirred for 30 min, then the
1-◦bromohexane (0.45 ml, 1.8 mmol) was added dropwise at
0 C. The solution was allowed to warm to room temperature
and the reaction mixture was stirred overnight. The crude
mixture was washed with aqueous sodium hydrogen carbonate
(2 × 20 ml) and brine (20 ml). The organic layer was dried over
MgSO4 and the solvent was removed in vacuo to give a pale
yellow oil purified by column chromatography using petroleum
ether–ethyl acetate (9 : 1) as eluent, to give 0.438 g (72%) as
◦
(7.8 mmol) in toluene at 0 C, so that the temperature did not
exceed 10 ◦C. After 1 h, a solution of 2 g of ethyl 1,4-dibenzyl-
2-piperazinecarboxylate (5.9 mmol, see below for preparation)
in toluene (10 ml) was added slowly at room temperature. The
reaction mixture was refluxed for 4 h, then stirred overnight
at room temperature. The reaction mixture was cooled and
treated dropwise with 50 ml of water–MeOH (50 : 50, v/v). After
filtration, the crude mixture was extracted with dichloromethane
(3 × 50 ml), washed with brine (2 × 30 ml) and water (20 ml)
and dried over MgSO4. Evaporation of the solvents gives a waxy
white solid, which was purified by column chromatography using
petroleum ether–ethyl acetate (8 : 2) as◦eluent, to give 1.51 g
1
1
a colourless oil. H NMR (CDCl3, 300 MHz) d 0.79 (3H, t, J
(74%) of a white powder. m.p. 119–120 C; H NMR (CDCl3,
7.0 Hz), 1.11–1.27 (6H, m), 1.48 (2H, m), 2.10–2.23 (3H, m),
2.45–2.49 (1H, m), 2.59–2.69 (3H, m), 3.26–3.32 (3H, m), 3.36–
3.47 (3H, m), 3.59 (1H, dd, J 4.3 Hz, 10.0 Hz), 4.00 (1H, d
J 13.5 Hz), 7.24–32 (10H, m); 13C NMR (CDCl3, 100 MHz)
d 14.14, 23.02, 26.23, 29.95, 32.06, 51.12, 53.25, 56.80, 60.10,
63.40, 71.85, 127.16, 127.36, 128.56, 129.53, 138.56, 139.56; m/z
381.2904 (expected 381.2906); Anal. Calcd. for C25H36N2O:C,
78.90; H, 9.53; N, 7.36%. Found C, 79.31; H, 10.50; N, 7.36%.
300 MHz) d 0.95 (3H, t, J 7.5 Hz), 1.56 (2H, sextuplet, J 7.1
Hz), 2.26–2.36 (3H, m), 2.39 (1H, d, J 1.9 Hz), 2.60 (1H, m),
2.62 (1H, d, J 3.5 Hz), 2.74–3.50 (6H, m) 3.81 (1H, d, J 13.5
Hz), 7.29–7.34 (10H, m); 13C NMR (CDCl3, 100 MHz) d 11.95,
23.41, 41.02, 50.04, 52.99, 56.55, 60.79, 63.18, 66.29, 127.70,
128.83, 129.11, 129.62, 137.86, 138.34, 172.08; m/z 352.2381
(expected 352.2389); Anal. calcd. for C22H29N3O:C, 75.18; H,
8.32; N, 11.96%. Found C, 75.00; H, 8.40; N, 12.01%.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6
1 2 1 3

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2-Hydroxymethylpiperazine (1f)18.
A
solution of 1–4-
2ꢀ-Hexoxymethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2c). Pre-
pared from diamine 1c and C60 by the general photochemical
procedure described above: 1H NMR (CDCl3, 300 MHz) d 0.89
(3H, t, J 7.1 Hz, CH3), 1.29 (2H, br s, CH2), 1.45 (6H, br s, 3 ×
CH2), 3.31 (1H, dd, J 7.0 Hz, 14.0 Hz, H3exo), 3.57 (1H, ddd, J
4.8 Hz, 8.9 Hz, 14.9 Hz, H5exo), 3.84 (1H, ddd, J 5.3 Hz, 11.6 Hz,
14.6 Hz, H6exo), 3.97 (2H, s, OCH2[Hexyl]), 4.52–4.61 (2H, m,
H5/6endo), 4.70 (1H, m, H3endo), 4.73 (1H, dd, J 6.0 Hz, 11.5 Hz,
CH2O), 4.93 (1H, dd, J 7.6 Hz, 11.5 Hz, CH2O), 5.14 (1H,
m, H2endo); 13C NMR (CDCl3/CS2, 100 MHz) d 14.38, 23.02,
25.65, 29.85, 31.95, 40.75, 47.43, 50.48, 52.65, 66.40, 77.41,
78.06, 136.78, 137.16, 139.54, 139.59, 139.68, 139.72, 140.59,
140.82 (2C), 141.58, 141.61, 141.64, 141.68, 142.00 (2C), 142.03,
142.40, 142.42 (2C), 142.43, 142.45 (2C), 144.36 (2C), 144.40,
144.94, 144.96, 145.07 (4C), 145.11, 145.28 (2C), 145.38, 145.41,
145.43, 145.49 (2C), 145.53 (3C), 145.55, 145.83 (3C), 145.86
(3C), 146.18 (2C), 146.21 (3C), 147.69, 147.73, 150.65; m/z 919
(MH+, expected 919.2).
2ꢀ-Amidocarboxypiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2d). Pre-
pared from diamine 1d and C60 by the general photochemical
procedure described above: 1H NMR (CDCl3, 300 MHz) d 3.47–
3.74 (2H, m, H4exo + H5exo), 4.10 (1H, dd, J 7.0 Hz, 14.0 Hz,
H3endo), 4.22 (1H, dd, J 7.2 Hz, 14.4 Hz, H3exo), 4.41–4.48 (1H,
m, H5/H6endo), 4.53–4.62 (2H, m, H5/H6endo +NH2), 5.28–5.35
(1H, m, H3endo), 5.78 (1H, br, NH); 13C NMR (CDCl3/Cs2, 100
MHz) d 41.23, 42.68, 47.74, 49.31, 78.28, 79.07, 136.96, 137.03,
137.78, 137.85, 139.92, 140.04, 140.20, 140.28, 141.03, 141.11,
141.39, 141.41, 142.00, 142.05, 142.11, 142.18, 142.36, 142.42,
142.48, 142.52, 142.90 (3C), 142.92, 142.95 (2C), 144.69, 144.80,
144.87, 145.02, 145.36, 145.43, 145.56 (2C), 145.58, 145.76,
145.86 (2C), 145.90, 146.03 (2C), 146.30, 146.33 (2C), 146.36,
146.63, 146.65, 146.71 (2C), 148.14, 145.25, 150.57, 150.82,
151.76, 15194, 173.77; m/z 849 (MH+, expected 848.1).
2ꢀ-Propylamidocarboxypiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2e).
Prepared from diamine 1e and C60 by the general photochemical
procedure described above. 1H NMR (CDCl3, 300 MHz) d 1.08
(3H, t, J 7.3 Hz, CH3), 1.72 (2H, sextuplet, J 7.4 Hz, CH2), 3.43
(1H, q, J 6.5 Hz, NCH2), 3.49–3.65 (3H, m, NCH2 + H5/H6exo),
4.25 (1H, dd, J 6.8 Hz, 13.9 Hz, H3exo), 4.37–4.43 (1H, m,
H5/H6endo), 4.54–4.64 (2H, m, H5/H6endo + H3endo), 5.31 (1H, t, J
7.7 Hz, H2endo); 13C NMR (CDCl3/CS2, 100 MHz) d 11.74, 23.3,
41.43, 42.12, 46.85, 48.03, 56.71, 77.29, 78.19, 136.97, 137.03,
137.78, 137.84, 139.91, 140.03, 140.19, 140.27, 141.03, 141.10,
141.38, 141.41, 141.99, 142.04, 142.11, 142.17, 142.36, 142.41,
142.46, 142.51, 142.89 (2C), 142.91, 142.94 (2C), 144.69, 144.79,
144.85, 145.01, 145.36, 145.42, 145.55 (2C), 145.58, 145.89,
146.02 (2C), 146.04 (2C), 146.29, 146.35, 146.62, 146.64, 146.70
(2C), 148.14, 148.25, 150.57, 150.82, 151.74, 151.92, 170.58; m/z
890 (MH+, expected 890.1).
2ꢀ-Hydroxymethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2f). Pre-
pared from diamine 1f and C60 by the general photochemical
procedure described above: 1H NMR (CDCl3, 300 MHz) d 2.77
(1H, br, OH), 3.10 (1H, dd, J 6.8 Hz, 13.4 Hz, H3exo), 3.52 (1H,
m, H5exo), 3.85 (1H, ddd, J 5.3 Hz, 11.8 Hz, 14.5 Hz, H6exo), 4.11
(1H, m, CH2O), 4.25 (1H, dd, J 10.0 Hz, 10.0 Hz, CH2O), 4.42–
4.54 (1H, m, H5/H6endo), 4.54–4.68 (2H, H5/H6endo+H3endo),
5.11 (1H, m, H2endo); 13C NMR (CDCl3/CS2, 100 MHz) d 39.44,
47.54, 50.32, 54.98, 62.38, 78.40, 80.04, 137.20 (2C), 137.33 (2C),
137.65, 137.78 (2C), 140.01, 140.08 (2C), 140.14 (2C), 140.15,
141.07 (2C), 141.17 (2C), 141.29, 142.02, 142.11(2C), 142.46,
142.88 (2C), 142.90, 142.95, 144.82 (2C), 144.92, 145.41, 145.46,
145.56, 145.63 (2C), 145.70 (2C), 145.87 (2C), 145.89, 145.93
(2C), 146.00 (2C), 146.33 (3C), 146.40, 146.64 (4C), 146.67 (2C),
151.03 (2C), 151.38, 151.76, 151.91; m/z 834 (MH+, expected
834.08).
dibenzyl-2-(hydroxymethyl)piperazine (1 g, 3.3 mmol, see below
for preparation) in ethanol (10 mL) was treated with 10% Pd/C
under an H2 atmosphere overnight at room temperature. The
mixture was filtered through celite before removing the solvent
in vacuo, to give 392 mg (95%) of the title compound as an
off-white powder The material was used in the next step without
purification. m.p. 95–96 ◦C; 1H NMR (300 MHz) d 3.38 (2H, dd,
J 2.2 Hz, 7.0 Hz), 2.94–2.68 (7H, m), 2.45 (1H, t, J 7.0 Hz) 13
C
NMR (75 MHz) d 46.7 (2C), 49.0, 57.6, 64.4. Spectroscopic data
and melting point are in line with that previously reported.18
1-4-Dibenzyl-2-(hydroxymethyl)piperazine18. Prepared by
modification to the procedure of Rondu et al.;18 A stirred
suspension of LiAlH4 (7.5 g, 22 mmol) in dry ether (30
mL) was cooled to 0 ◦C and 3.34 g (88 mmol) of ethyl 1,4-
dibenzylpiperazine-2-carboxylate (see below for preparation)
in ether (30 mL) was added slowly. The mixture was stirred
overnight at room temperature, then cooled to 0 ◦C and
treated carefully with aqueous sodium hydrogen carbonate.
The solution was extracted with CH2Cl2 (2 × 50 mL) and
the organic extract was dried over MgSO4. After the solvent
was removed, recrystallization of the crude product from ethyl
acetate–hexane afforded 5.◦8 g (88%) of the title compound as a
1
white powder. m.p. 72–73 C; H NMR (300 MHz) d 7.36–7.2
(10H, m, Ar–H), 4.06 (1H, dd, J 11.2, 2.9 Hz), 3.95 (1H, d,
J 13.2 Hz), 3.59 (1H, dd, J 11.2, 2.9 Hz), 3.48 (1H, d, J 13.2
Hz), 3.78 (1H, br s), 3.47 (2H, s), 2.95–2.92 (1H, m), 2.69–2.31
(6H, m); 13C NMR (75 MHz) d 50.2, 52.8, 56.4, 58.4, 58.9, 62.5,
63.6, 127.0–129.1, 137.6, 138.4. Spectroscopic data and melting
point are in line with those previously reported.18
Ethyl 1-4-dibenzylpiperazine-2-carboxylate. Prepared ac-
cording to the procedure of Rondu et al.;18 3.67 mL of
ethyl 2,3-dibromopropionate (25 mmol) was added drop-
◦
wise to a hot (80 C) toluene solution (75 ml) of N,Nꢀ-
dibenzylethylenediamine 6 g (24 mmol), 8.36 mL (60 mmol) of
triethylamine. The reaction mixture was refluxed overnight and
then cooled. The reaction mixture was washed with aqueous
sodium hydrogen carbonate (2 × 50 mL) and brine (1 × 50
mL). The organic layer was dried over MgSO4 and the solvent
removed in vacuo to give a red oil which was purified by column
chromatography using petroleum ether–ethyl acetate (9 : 1) as
eluent, to give 7.66 g (90%) of the title compound as a colorless
1
oil. H NMR (300 MHz), d 4.12 (2H, q, J 7.0 Hz), 3.84 (1H,
d, J 13.1 Hz), 3.52–3.58 (2H, m), 3.35 (1H, d, J 12.8 Hz), 3.23
(1H, dd, J 11.8 Hz, 6.5 Hz), 2.99 (1H, m), 2.65 − 2.24 (5H, m);
13C NMR (75 MHz), d 14.6, 49, 53.4, 55.9, 60.0, 60.8, 63.0, 63.2,
127.4–129.5, 138.3, 138.5, 172.5. Spectroscopic data are in line
with those previously reported.18
Piperazine–C60 adduct 2a4a. Prepared by the general pho-
tochemical procedure described above, but using only 1 eq.
piperazine 1a (0.11 mmol). Irradiation period of 18 h. Yield
75%. Spectroscopic data are in line with literature values.4a
2ꢀ-Methylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2b)8. Prepared
from diamine 1b and C60 by the general photochemical
procedure described above. Irradiation period of 64 h. Yield
1
41%. H NMR (CDCl3, 300 MHz) d 1.78 (3H, d, J 6.8 Hz,
CH3), 3.19 (1H, dd, J 6.4 Hz, 13.7 Hz, H3exo), 3.57 (1H, dddd, J
4.0 Hz, 8.6 Hz, 8.6 Hz, 11.5 Hz, H5exo), 3.91 (1H, ddd, J 5.4 Hz,
8.6 Hz, 14.1 Hz, H6exo), 4.45–4.60 (2H, m, H5endo+H6endo), 4.72
(1H, m, H3endo), 4.94 (1H, ddd, J 6.4 Hz, 6.8 Hz, 13.4 Hz, H2endo)
;
13C NMR (CDCl3/CS2, 100 MHz) d 19.48, 39.17, 47.08, 48.93,
55.11, 77.54, 80.53, 137.85, 137.97, 138.06, 138.28, 140.58,
140.65, 140.67, 141.72, 141.83, 141.93, 142.61, 142.64 (2C),
142.68 (2C), 143.01 (2C), 143.03, 143.42 (3C), 143.43 (3C),
143.48, 145.46 (2C), 145.51 (2C), 146.06 (3C), 146.08 (2C),
146.34 (2C), 146.42 (2C), 146.45, 146.67, 146.75, 146.79 (3C),
146.81 (2C), 146.92 (2C), 147.16 (2C), 147.18 (2C), 148.64,
148.67, 152.93, 153.20, 153.35, 153.53; m/z 818.
trans-2ꢀ,5ꢀ-Dimethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2g). Pre-
pared from diamine 1g and C60 by the general photochemical
procedure described above, but using 5 eq. diamine (0.55 mmol).
1 2 1 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6

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1H NMR (CDCl3, 300 MHz) d 1.82 (3H, d, J 6.9 Hz, CH3exo),
1.97 (3H, d, J 7.1 Hz, CH3endo), 3.25 (1H, dd, J 4.8 Hz, 13.9 Hz,
H3exo), 3.82 (1H, dd, J 8.0 Hz, 9.0 Hz, H5exo), 4.15 (1H, dd,
J 9.3 Hz, 14.6 Hz, H6exo), 4.43 (1H, ddd, J 1.3 Hz, 9.5 Hz,
14.6 Hz, H6endo), 4.76 (1H, m, H2endo), 5.03 (1H, ddd, J 0.9 Hz,
9.3 Hz, 13.9 Hz, H3endo); 13C NMR (CDCl3/CS2, 100 MHz)
d 20.96, 23.71, 47.36, 49.70, 54.46, 60.03, 77.23, 77.36 (part.
obsc.), 136.64, 137.38 (2C), 137.42, 139.80, 139.86, 139.87,
140.02, 140.63, 140.82, 140.95, 141.23, 141.84, 141.91, 141.97,
142.03, 142.34, 142.37, 142.39, 142.72, 142.73, 142.77, 142.94,
142.99, 143.04, 144.64, 144.67, 144.91, 145.00, 145.32, 145.38,
145.41, 145.42, 145.44, 145.45, 145.50, 145.59, 145.66, 145.77
(2C), 145.80, 145.83, 145.85, 146.13 (2C), 146.20 (2C), 146.42,
146.54 (2C), 146.56 (2C), 148.03, 148.07, 151.86, 152.09, 153.33,
153.46; m/z 833 (MH+, expected 833.1).
146.29, 146.31, 146.62, 146.64, 148.16, 148.20, 151.18, 151.32,
151.75, 151.90, 165.98; m/z 1017 (expected 1017.02).
2ꢀ -(tert-Butyldimethylsiloxymethyl)piperazino[1ꢀ,4ꢀ:1,2][60]-
fullerene (2j). To a solution of adduct 2f (10.0 mg, 12 lmol)
and imidazole (3 mg, 48 lmol) in a mixed solvent (1 : 1
dichloromethane–chlorobenzene) (3 mL) was added TBDMSCl
(6 mg, 48 lmol). The reaction mixture was stirred overnight
at room temperature and the solvent was removed in vacuo to
give a brown solid purified by column chromatography using
dichloromethane–ethyl acetate (70 : 30) as eluent, to give 7.6 mg
1
(67%) of the title compound 2j as a brown powder. H NMR
(CDCl3, 300 MHz) d 0.24 (6H, s, CH3), 1.04 (9H, s, CH3),
3.61–3.70 (2H, m, H3exo+ H5exo/ H6exo), 3.96–4.04 (1H, m,
H5exo/ H6exo), 4.30 (1H, dd, J 5.1 Hz, 10.4 Hz, 1H of OCH2),
4.40 (1H, dd, J 5.4 Hz, 10.3 Hz, 1H of OCH2), 4.46–4.51 (2H,
m, H5endo+ H6endo), 4.56–4.62 (1H, m, H6exo), 4.87 (1H, q, J
7.5 Hz, H2endo); 13C NMR (CDCl3/CS2, 100 MHz) 14.14 (CH3),
26.02 (CH3), 41.88 (CH2, C-6), 47.20 (CH2, C-5), 49.99 (CH2,
C-3), 54.97 (CH, C-2), 65.60 (OCH2), 78.14, 80.54, 137.27,
137.33, 137.66, 139.93, 139.97, 140.08, 140.11, 141.09, 141.21,
141.27 (2C), 141.28, 142.01, 142.03 (2C), 142.05, 142.08, 142.40
(2C), 142.43, 142.82 (3C), 142.90 (2C), 144.82, 144.85 (2C),
144.88 (2C), 145.45, 145.50 (3C), 145.53, 145.74, 145.81, 145.82,
145.87, 145.90 (2C), 145.94 (2C), 145.97 (2C), 146.25 (2C),
146.27 (2C), 146.59 (2C), 146.61 (2C), 146.63 (2C), 148.13,
148.17, 151.65, 151.72; m/z 949 (expected 949.17).
2ꢀ-p-Toluenesulfonylmethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2k).
To a solution of adduct 2f (10.0 mg, 12 lmol), triethylamine
(8 lL, 60 lmol) in a mixed solvent (1 : 1 dichloromethane–
chlorobenzene, 3 mL) was added tosyl chloride (11 mg, 60 lmol).
The reaction mixture was stirred for 48 h at room temperature
andthesolventremoved invacuotogiveabrownsolid, whichwas
purified by column chromatography using toluene–ethyl acetate
(70 : 30) as eluent, to give 6.4 mg (54%) of the title compound 2k
as a brown powder. 1H NMR (CDCl3, 300 MHz) d 2.51 (3H, s,
CH3), 3.28 (1H, dd, J 6.6 Hz, 13.9 Hz, H3), 3.45–3.53 (1H, m,
H5/6), 3.61–3.69 (1H, m, H5/6), 4.37–4.57 (3H, m, H5 + H6
+ H3), 4.62 (1H, dd, J 6.5 Hz, 10.4 Hz, 1H of OCH2), 4.69
(1H, dd, J 6.8 Hz, 10.3 Hz, 1H of OCH2) 4.93–5.00 (1H, m,
H2), 7.39 (2H, d, J 8.0 Hz, Ar), 7.90 (2H, d, J 8.1 Hz, Ar);
13C NMR (CDCl3/CS2, 100 MHz) d 21.99, 41.07 (CH2, C-5/6),
47.37 (CH2, C-5/6), 50.35 (CH2, C3), 52.65 (CH, C2), 70.31
(OCH2), 78.06, 80.18, 128.21 (CH, Ar), 129.95 (CH, Ar), 137.14,
137.35, 137.65, 138.11, 139.75, 139.99 (2C), 140.17, 140.19,
140.20, 141.05, 141.18, 141.20, 141.28, 142.11 (2C), 142.14 (2C),
142.14, 142.20, 142.21, 142.48, 142.49, 142.52, 142.53, 142.93
(4C), 142.93 (2C), 144.87 (2C), 144.94 (2C), 145.43, 145.45,
145.55 (2C), 145.58, 145.69, 145.72, 145.78, 145.92, 145.97 (2C),
146.01 (2C), 146.10, 146.31 (2C), 146.34 (2C), 146.66, 146.67
(3C), 146.70 151.22, 151.35; m/z 989 (expected 989.08).
2ꢀ-Acroylmethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2h). To a
solution of adduct 2f (10.0 mg, 12 lmol), triethylamine (7 lL,
50 lmol) and DMAP (0.4 mg, 1 lmol) in a mixed solvent (1 : 1
dichloromethane–chlorobenzene) (3 mL) was added dropwise
acroyl chloride (5 lL, 72 lmol). The reaction mixture was
stirred overnight at room temperature and washed with aqueous
sodium hydrogen carbonate (1 × 5 mL) and brine (2 × 5 mL).
The organic layer was dried over MgSO4 and the solvent was
removed in vacuo to give a brown solid purified by column
chromatography using toluene–ethyl acetate (8 : 2) as eluent, to
give 7.6 mg (71%) of the title compound 2h as a brown powder.
1H NMR (CDCl3, 300 MHz) d 3.35 (1H, dd, J 6.8 Hz, 13.9 Hz,
H3exo), 3.56–3.63 (1H, m, H5exo), 3.81–3.89 (1H, m, H6exo), 4.48–
4.59 (2H, m, H5endo+ H6endo), 4.66–4.76 (1H, m, H3endo), 4.79
(1H, dd, J 6.6 Hz, 11.5 Hz, 1H of OCH2), 4.90 (1H, dd, J
7.0 Hz, 11.3 Hz, 1H of OCH2), 5.16 (1H, q, J 7.5 Hz, H2endo),
=
5.94 (1H, dd, J 1.4 Hz, 10.4 Hz, CH2), 6.29 (1H, dd, 10.4 Hz,
17.2 Hz, HC ), 6.56 (1H, dd, 1.3 Hz, 17.2 Hz, CH2); 13C NMR
(CDCl3/CS2, 100 MHz) 40.60 (CH2, C-6), 47.21 (CH2, C-5),
50.82 (CH2, C-3), 52.53 (CH, C-2), 65.32 (OCH2), 78.00, 80.21,
=
=
=
=
128.09 (HC ), 131.66 (H2C ), 137.24, 137.30, 137.58, 137.66,
139.95, 140.03, 140.09, 140.14, 141.08, 141.18, 141.25 (2C),
141.27, 142.03, 142.06, 142.11, 142.42 (2C), 142.45, 142.85 (2C),
142.87 (2C), 142.91 (3C), 144.82 (2C), 144.85, 144.88, 145.41,
145.53 (2C), 145.56, 145.72, 145.78, 145.85 (2C), 145.95 (2C),
145.96, 146.28 (2C), 146.29 (2C), 146.61 (2C), 146.64, 148.16,
148.20, 151.22, 151.37, 166.27; m/z 889 (expected 889.09).
2ꢀ-p-Bromobenzoylmethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2i).
To a solution of adduct 2f (25.0 mg, 30 lmol), triethylamine
(16 lL, 0.12 mmol) and DMAP (1 mg, 3 lmol) in a mixed
solvent (1 : 1 dichloromethane–chlorobenzene, 3 mL) was added
dropwise p-bromobenzoyl chloride (26 mg, 0.12 mmol). The
reaction mixture was stirred for 35 h at room temperature and
washed was washed with aqueous sodium hydrogen carbonate
(1 × 5 ml) and brine (2 × 5 ml). The organic layer was dried
over MgSO4 and the solvent was removed in vacuo to give a
brown solid purified by column chromatography using toluene–
ethyl acetate (9 : 1) as eluent, to give 19 mg (62%) of the title
compound 2i as a brown powder. 1H NMR (CDCl3, 300 MHz) d
3.40 (1H, dd, J 6.8 Hz, 14.2 Hz, H3exo), 3.60–3.65 (1H, m, H5exo),
3.87–3.93 (1H, m, H6exo), 4.51–4.61 (2H, m, H5endo+ H6endo),
4.72–4.78 (1H, m, H3endo), 4.93 (1H, dd, J 6.7 Hz, 11.2 Hz, 1H
of OCH2), 5.08 (1H, dd, J 7.0 Hz, 11.3 Hz, 1H of OCH2), 5.22–
5.29 (1H, m, H2endo), 7.63 (2H, d, J 8.6 Hz, Ph), 8.02 (2H, d,
J 8.5 Hz, Ph); 13C NMR (CDCl3/CS2, 100 MHz) 40.67 (CH2,
C6), 47.28 (CH2, C5), 50.86 (CH2, C3), 52.60 (CH, C2), 65.96
(OCH2), 78.00, 80.21, 128.30 (CH, Ph), 128.4 (C, C-ipso), 128.75
(C, C-ipso), 129.11 (CH, Ph), 131.35 (CH, Ph), 131.91, (CH, Ph),
137.24, 137.30, 137.59, 137.69, 139.97, 140.07, 140.11, 140.15,
141.06, 141.48, 141.25, 141.27, 142.04 (2C), 142.07, 142.11,
142.41 (3C), 142.44, 142.86 (3C), 142.88, 142.92 (3C), 144.82
(3C), 144.85, 144.88, 145.38, 145.51 (2C), 145.54, 145.56, 145.68,
145.77, 145.86 (3C), 145.89, 145.93, 145.95, 145.96, 146.28 (2C),
2ꢀ-Methylsulfonylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene(2l). Adduct
2l was prepared from the adduct 2f (10 mg) by the same
procedure as used for the tosylate adduct 2k, using 5 eq. of
methanesulfonyl chloride (5 lL, 60 lmol). The reaction mixture
was stirred for 48 h at room temperature and the solvent removed
in vacuo to give a brown solid, which was purified by column
chromatography using toluene–ethyl acetate (80 : 20) as eluent,
to give 5 mg (46%) of the title compound 2l as a brown powder.
1H NMR (CDCl3/CS2, 300 MHz) d 3.24–3.31 (4H, m), 3.53–
3.60 (1H, m), 3.80–3.88 (1H, m), 4.50–4.76 (4H, m), 4.68 (1H,
m), 4.95–5.00 (1H, m), 5.14–5.25 (1H, m); m/z 913 (expected
913.06). A 13C NMR spectrum of adduct 2l could not be
obtained due to the relative insolubility of the mesylate adduct
in all common deuterated solvents, including admixtures with
CS2.
2ꢀ-Iodomethylpiperazino[1ꢀ,4ꢀ:1,2][60]fullerene (2m). To
a
solution of mesylate 2l (20 mg, 21 lmol) in chlorobenzene
(3 mL) was added a solution of sodium iodide (15 mg, 0.1 mmol)
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6
1 2 1 5

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in acetone (2 mL). The reaction mixture was heated to refluxed
for 48 h and the solvents removed in vacuo to give a brown
solid, which was purified by column chromatography using
dichloromethane–ethyl acetate (90 : 10) as eluent, to give 9 mg
(44%) of the title compound 2m as a brown powder. 1H NMR
(CDCl3, 300 MHz) d 1H NMR 3.30 (H, dd, J 6.5 Hz, 14.0 Hz),
3.49–3.59 (1H, m), 3.69–3.83 (3H, m,), 4.38–4.56 (2H, m), 4.70–
4.79 (1H, m), 5.05 (1H, q, J 8.1 Hz); m/z 945 (expected 944.98).
A 13C NMR spectrum of adduct 2m could not be obtained due
to the relative insolubility of the mesylate adduct in all common
deuterated solvents, including admixtures with CS2.
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Acknowledgements
The authors would like to thank Mr Simon Thorpe and Ms
Sharon Spey at University of Sheffield for assistance with
mass spectrometry and the TMR networks USEFULL and
BIOFULL (CT 960126 and 980192) for financial support
for M. J. We alsoacknowledgethe financialsupportofthe School
of Chemistry, University of Exeter.
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Imperial College Press, 1999, p. 45.
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 2 0 9 – 1 2 1 6