Reactivity of [60]Fullerene with primary nitro compounds: Addition or catalysed condensation to isoxazolo[60]fullerenes

Article abstract of DOI:10.1002/ejoc.201402990

The catalysed condensation of [60]fullerene with ethyl nitroacetate (1b) or analogous activated nitro derivatives to afford isoxazolino[60]fullerenes has been achieved in both homogeneous and heterogeneous conditions. This direct synthetic approach is more convenient than previous methods. Model reactions with electron-poor dipolarophiles led to either condensation to isoxazolines or to conjugate addition products, depending on the nitro compound and catalyst. The former product was favoured by the use of Cu^II in the catalytic system. Conversely, [60]fullerene underwent catalytic condensation, even in the absence of copper(II) salts, only with activated nitro compounds and addition only with nitroalkanes in excess base. Note, the formal conjugated fullerene addition product was obtained in isomeric form, as previously reported. A possible explanation is presented for this contrasting behaviour.

Full text of DOI:10.1002/ejoc.201402990

Job/Unit: O42990
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Pages: 11
FULL PAPER
DOI: 10.1002/ejoc.201402990
Reactivity of [60]Fullerene with Primary Nitro Compounds: Addition or
Catalysed Condensation to Isoxazolo[60]fullerenes
Giacomo Biagiotti,[a,b] Stefano Cicchi, Francesco De Sarlo, and Fabrizio Machetti*
[b]
[b]
[a]
In memory of Giulio Del Giusto on the 100th anniversary of his birth
Keywords: Cycloaddition / Condensation reactions / Fullerenes / Copper / Nitro compounds
The catalysed condensation of [60]fullerene with ethyl nitro-
acetate (1b) or analogous activated nitro derivatives to afford
product was favoured by the use of CuII in the catalytic sys-
tem. Conversely, [60]fullerene underwent catalytic conden-
isoxazolino[60]fullerenes has been achieved in both homo- sation, even in the absence of copper(II) salts, only with acti-
geneous and heterogeneous conditions. This direct synthetic
approach is more convenient than previous methods. Model
vated nitro compounds and addition only with nitroalkanes
in excess base. Note, the formal conjugated fullerene ad-
reactions with electron-poor dipolarophiles led to either con- dition product was obtained in isomeric form, as previously
densation to isoxazolines or to conjugate addition products,
depending on the nitro compound and catalyst. The former
reported. A possible explanation is presented for this con-
trasting behaviour.
so that even Grignard reagents are able to add to it.[13]
Thus, fulleroisoxazolines have been obtained as a result of
the 1,3-dipolar cycloadditions to [60]fullerene of either
Introduction
[
60]Fullerene is one of the most popular “artificial
[
1–4]
molecules"
due to its unique eye-catching geometry as
[
14,15]
nitrile oxides
or silylnitronates followed by elimi-
well as its peculiar chemical and physical properties. This
[
16]
nation. These reactions are usually carried out in toluene
has stimulated intense and thorough studies of its reactiv-
[
17]
owing to the slight solubility of [60]fullerene but recently
solvents in which this compound is more soluble have been
ity[
5,6]
and the applications of its functionalised derivatives
[
7,8]
in different fields.
In addition, [60]fullerene is a useful
[
18]
employed.
model for the development of new processes for the func-
tionalisation of carbon nanomaterials.[9] Hence, the devel-
opment of methods for the functionalisation of fullerenes
is of great significance and tremendous efforts have been
dedicated to this goal over the past few decades, as docu-
mented in the large number of papers and reviews that have
The intermediate nitrile oxides were produced either
[
15]
from hydroxamoyl chlorides
or by dehydration of pri-
[
19]
mary nitro compounds. However, the latter procedure is
now superseded by the catalytic condensation of the same
starting materials. This protocol, performed in a single pot,
avoiding the use of dehydrating reagents and the formation
of byproducts derived from them, might be included in the
so-called click-chemistry processes.
reactions have been successfully carried out with other
dipolarophiles either in chloroform, ethanol
[
7a,10]
been published.
have a privileged position, particularly those of dienes or
Among these reactions, cycloadditions
[11]
[
20]
These condensation
[
12]
1
,3-dipoles with high-energy HOMOs because the pecu-
liar double bond encountered in fullerenes is electrophilic
[
21–23]
or
[
24,25]
water,
and the solvent employed has been shown to
[a] Istituto di Chimica dei Composti Organometallici del Consiglio
Nazionale delle Ricerche, c/o Dipartimento di Chimica Ugo affect both the mechanism and the results of the reaction.
Schiff,
[26,27]
In view of the possible application of this protocol
to
Via della Lastruccia 13, 50019 Sesto Fiorentino (Firenze), Italy
E-mail: fabrizio.machetti@unifi.it
fabrizio.machetti@cnr.it
[60]fullerene, with its poor solubility in most common sol-
vents, we decided to investigate the course of some model
reactions under various conditions before attempting con-
http://www.iccom.cnr.it/
http://www2.chim.unifi.it/
[
b] Dipartimento di Chimica Ugo Schiff, Università degli Studi di densation reactions with [60]fullerene. Subsequently, the
Firenze,
known addition of nitroalkanes and other unactivated pri-
Via della Lastruccia 13, 50019 Sesto Fiorentino (Firenze), Italy
mary nitro compounds in basic conditions will be reconsid-
Supporting information for this article is available on the
[
28]
WWW under http://dx.doi.org/10.1002/ejoc.201402990.
ered.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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G. Biagiotti, S. Cicchi, F. De Sarlo, F. Machetti
FULL PAPER
Results and Discussion
Model Reactions
(N-methylpiperidine, 0.5 equiv.) was usually used in these
reactions (entries 4–6).
II
Table 2. Model reactions under Cu /NMP catalysis in various sol-
We performed model experiments with different solvents
and catalyst at various concentrations. Chloroform, toluene,
chlorobenzene and 1-chloronaphthalene were chosen as sol-
vents in which [60]fullerene has increasing solubility (0.16,
[a,b]
vents.
Entry R1
R2
Solvent[c] Base [m] Yield [%][d]
2
3
1
2
3
4
5
6
7
8
9
CH
CH
CH
CH3
CH
CH
CO
CO
CO C H
CO
CO C H
3
3
3
CONH
CONH
CONH
2
2
2
A
B
C
A
B
C
A
B
D
C
A
B
C
C
C
0.15
0.15
0.15
0.15
0.15
77
0
0
0
0
0
0
0
0
0
0
8
4
11
22
0
2
0
.8, 7.0 and 51 mg/mL or 0.00022, 0.0039, 0.0097 and
.071 m, respectively).[
17]
0
50[
11
26
99
98
98
45
94
55
69
53
98
e]
We have previously shown that compounds containing
2
CO CH
3
3
3
electron-deficient double bonds, on treatment with “active”
primary nitro compounds (i.e., bearing an EWG geminal to
the nitro group) in chloroform, undergo either cycload-
dition/condensation to give isoxazole derivatives 2 or conju-
3
CO
CO
2
CH
CH
3
2
0.15
[f]
2
C
C
2
H
H
5
5
5
5
5
5
5
CONH
CONH
2
0.030
0.030
0.030
0.030
0.030
0.030
0.030
0.030
0.030
2
2
2
2
2
CONH2
CONH
CO CH
gate addition to yield 3, depending on the catalyst employed 10
2
C
2
H
2
and the Michael acceptor (Scheme 1).[
29]
11
2
2
2
2
2
2
2
3
3
3
3
[g]
12
13
14
15
CO
CO
CONHCH
CONHCH
C
C
H
H
CO
CO
CO
2
CH
2
CH
2
CH
3
3
CONH
2
0
[
1
a] NMP: N-methylpiperidine. [b] Reagents and conditions: 0.75 m
, 0.30 m dipolarophile, 0.015 m Cu , 24 h; see Exp. Sect. for more
II
details. [c] A: chloroform, B: toluene, C: 1-chloronaphthalene, D:
chlorobenzene. [d] The spectroscopic yields were determined by H
1
Scheme 1. Model reactions: competition between conjugate ad-
dition and cycloaddition/condensation between nitro compounds
and electron-poor alkenes.
NMR spectroscopy with the use of an internal standard. [e] Value
at 40 h. No product at 24 h. [f] The same experiment repeated in a
six-fold diluted reaction mixture gave a 42% spectroscopic yield.
After 120 h the spectroscopic yield was 78%. [g] The same experi-
ment repeated in a 75-fold diluted reaction mixture (0.0125 m 1b +
Thus, ethyl nitroacetate (1b) on catalysis by only
0
2
.004 m methyl acrylate) failed, no conversion being observed after
DABCO (1,4-diazabicyclo[2.2.2]octane) as base selectively
4 h.
2
underwent conjugate addition to give 3b (R = CONH or
2
CO CH ) not only in chloroform but in other solvents as
well (Scheme 1 and Table 1).
2
3
The failure of the condensation reactions in toluene and
1
-chloronaphthalene might be related to the poor solubility
II
of acrylamide and the Cu salt in these cases, whereas a
higher solubility is expected for reactions of activated nitro
Table 1. Model reactions of 1b and electron-poor dipolarophiles
[a,b]
with only base (DABCO) as catalyst (Scheme 1).
II
[31]
derivatives, for which Cu complexes are known. In fact,
Entry Solvent
R2
Yield [%][c]
the reaction of ethyl nitroacetate (1b) with acrylamide
2
3
Scheme 1, R2 = CONH ) under the usual conditions
(
2
2
1
2
3
4
5
6
chloroform
toluene
1-chloronaphthalene
chloroform
toluene
CONH
CONH
CONH
2
2
2
traces
53
99
87
68
83
80
(0.757 m 1b + 0.303 m acrylamide) gave the product 2b (R
0
0
2
2
0
=
(
3
CONH ) after 24 h at 60 °C in all the solvents considered
2
entries 7–10) with a minor amount of the addition product
CO
CO
CO
2
2
2
CH
CH
CH
3
3
3
2
b (R = CONH ) obtained in 1-chloronaphthalene (en-
2
2
1-chloronaphthalene
try 10). With methyl acrylate, both products 2b (R =
CO CH ) and 3b (R = CO CH ) were obtained from 1b,
the isoxazoline 2b (R = CO CH ) being predominant (en-
2
2
3
2
3
[
a] DABCO: 1,4-diazabicyclo[2.2.2]octane. [b] Reagents and condi-
2
tions: 1b (2.5 equiv.), DABCO (0.1 equiv.), 60 °C, 24 h; see the Exp.
2
3
Sect. for details. [c] The spectroscopic yields were determined by tries 11–13).
1
H NMR spectroscopy with the use of an internal standard.
The model reaction in chloroform, at the concentration
corresponding to fullerene solubility in 1-chloronaphtha-
Nitroalkanes did not react under these conditions. How- lene, was successful (Table 2, entry 7, footnote [f]). However,
ever, we have previously shown that on addition of a CuII the reaction between 1b and methyl acrylate in more dilute
salt to the base, the cycloaddition/condensation predomi- toluene solution (Table 2, entry 12, footnote [g]) failed.
nated in chloroform and not only active nitro compounds
N-Methylnitroacetamide (1c) in 1-chloronaphthalene se-
but also nitroalkanes underwent condensation selec- lectively gave the isoxazolines 2c (R2 = CO CH3 or
2
[
29,30]
tively.
Their reactions in various solvents with catalytic CONH ) provided the reactions with acrylamide and
2
II
Cu are reported in Table 2. The condensation of nitroeth- methyl acrylate were carried out at 80 °C whilst stirring (en-
[
25]
ane with acrylamide was successful in chloroform, but not tries 14 and 15). The amide 1c (m.p. 75–76 °C) is insolu-
in toluene or 1-chloronaphthalene (entries 1–3). With ble in 1-chloronaphthalene, but reactions are known to take
methyl acrylate, the condensation of nitroethane occurred place even in spite of heterogeneous conditions, especially
[
24,25]
slowly to give moderate yields after 24 h, and more base emulsions.
2
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Reactivity of [60]Fullerene with Primary Nitro Compounds
Synthesis of [60]Fulleroisoxazolines
ous functional groups to be anchored to fullerene (Table 3).
3
-Carbamoyl[60]fulleroisoxazolines (4c, 4d) have never been
The model reactions considered above (Table 2) showed
that condensations of nitro compounds can be successfully
carried out in 1-chloronaphthalene, even at a dipolarophile
concentration corresponding to [60]fullerene solubility
reported before. This interesting functionalisation can be
efficiently achieved by condensation of nitroacetamides 1c
and 1d with [60]fullerene under the usual conditions. N-
Methylnitroacetamide (1c) was obtained by aminolysis of
ethyl nitroacetate with aqueous methylamine in large excess,
(Table 2, entry 7, footnote [f]). Thus, [60]fullerene was
treated in 1-chloronaphthalene solution with ethyl nitro-
[
32]
as reported previously.
The amide 1d was prepared in
II
acetate (1b) in the presence of the Cu /NMP catalytic sys-
low yield by heating methyl nitroacetate with a slight excess
of tert-butyl (2-aminoethyl)carbamate in water/pyridine.
Better results were obtained by performing the reaction
with a four-fold excess of the amine in methanol at room
temperature for 3 days. Crude 1d can be purified by flash
chromatography (m.p. 120–121 °C, yield 32%), but washing
with hexane gave a product (m.p. 113–114 °C, yield 78%)
pure enough for further reaction. In both cases, the excess
amine was recovered in part.
Benzoylnitromethane (1e) reacted under the same condi-
tions in the presence of copper acetate to give the corre-
sponding 1:1 condensation product 4e in addition to minor
amounts of polyadducts (Table 3, entry 5).
tem. After 5 d at 60 °C and removal of solvent by column
chromatography, analysis of the products showed a con-
siderable yield of the condensation product 4b (Table 3),
but, unlike the model reactions, no conjugate adduct was
observed, even in the absence of a copper salt. Some con-
densation products in a 2:1 ratio were detected in the reac-
tion catalysed by only the base. Preliminary removal of the
solvent by distillation in vacuo was ruled out to avoid ex-
cessive heating, thus, 1-chloronaphthalene was separated
from the products by column chromatography.
Table 3. [60]Fulleroisoxazolines 4 obtained by copper/base-cata-
lysed condensation of nitro compounds 1 with [60]fullerene.[
a]
The [60]fulleroisoxazolines 4 are generally poorly soluble
in common deuteriated solvents used for NMR spec-
troscopy such as chloroform and acetone. In particular, the
severe insolubility of the amide 4c even with CS as a co-
2
solvent made it necessary to add 1-chloronapththalene as a
co-solvent for the acquisition of 13C NMR spectra.
Phosphonate [60]fulleroisoxazolines have been reported
Entry
1
R1
4
Yield [%]
[33]
only by Sinyashin and co-workers, who synthesised them
4[
b]
[c]
60
C
by the cycloaddition of (diisopropoxyphosphoryl)nitrile ox-
ide and [60]fullerene. Unlike other nitrile oxides, this reac-
tion gave two bis-adducts as the main products in addition
to the mono-adduct. The catalytic procedure described
herein with diethyl (nitromethyl)phosphonate (1f) led to
only the monoadduct 4f (Table 3, entry 6). Diethyl (nitro-
methyl)phosphonate (1f) was prepared by slight modifica-
1
2
3
1a
1b
1c
1d
CH
C(=O)OCH
C(=O)NHCH
C(=O)NHCH
OC(CH
C(=O)C
P(=O)(OCH
3
4a traces[d]
4b 31 (52)
4c 42 (66)
4d 28 (50)
–
2
CH
3
40
36
44
[e]
3
4
2 2
CH NHC(=O)
3 3
)
6
H
5
6
1e
1f
5
4e 38 (46)
4f 22 (53)
39
58
2 3 2
CH )
[
[
a] All the reactions were carried out with 50 mg (0.069 mmol) of
60]fullerene, nitro compound 1 (0.173 mmol), copper acetate
[34,35]
tions of previously reported procedures.
(
(
0.00345 mmol) and NMP (0.0069 mmol) in 1-chloronaphthalene
1.0–1.4 mL) at 60 °C unless otherwise stated; see Exp. Sect. for
details. [b] Yield of isolated product based on [60]fullerene; the val-
ues in parentheses are based on consumed [60]fullerene. [c] Reco-
vered by chromatography. [d] The main product was the oxime 5a
Reactions in Excess Base
(
see below), along with the corresponding bis- and tris-adducts; see
The reactions of [60]fullerene with various nitro com-
pounds in large excess of reagents and base (triethylamine)
Exp. Sect. for details. [e] Reaction carried out at 80 °C.
By using a gradient of suitable eluent, unreacted fuller- have previously been reported to afford hydroxy oximes 5,
ene, 1-chloronaphthalene and the products were collected which corresponds to the addition of a nitro compound to
[
28,36]
in sequence: yield of monoadduct 31%, or 52% based on [60]fullerene (Table 4).
The reaction was successful
consumed fullerene and 60% conversion (Table 3, entry 2). with nitroethane (1a)[37] in excess of base (35%, entry 1),
The same reaction carried out in toluene under the same whereas with a catalytic amount of base (triethylamine or
conditions disregarding solubility was successful, in spite of DABCO), the oxime was isolated in low yield (8 and 21%,
the heterogeneous conditions, with a yield of 18%; con- respectively) only after prolonged heating (Table 4 entries 2
sidering 48% conversion, the yield based on converted ful- and 3). On the other hand, activated nitro compounds 1b
lerene was 38%. Homogeneous conditions for the same re- and 1c in excess TEA led only to the decomposition of the
action in toluene would require extreme dilution of the rea- nitro compounds, whereas with a catalytic amount of base
gent and catalyst with loss of reactivity, as we evidenced in (DABCO) the dehydrated cycloadducts 4b and 4c were the
our model reactions (Table 2, entry 7, footnote [g]).
The procedure in 1-chloronaphthalene established above, When a catalytic amount of Cu was added to the base, the
applied to other activated nitro compounds, allowed vari- formation of poly-cycloadducts decreased (Table 3 and 4).
main products with minor amounts of poly-cycloadducts.
II
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G. Biagiotti, S. Cicchi, F. De Sarlo, F. Machetti
Table 4. Reactions of nitro compounds 1 with [60]fullerene in the presence of base under a variety of conditions.
FULL PAPER
Entry
1 (equiv.)[a]
Solvent[b]
Conditions
Base (equiv.)[a]
Products [%]
[
c]
4
5
C
60
1[d]
2
3
4
5
6
7
8
a (20)
a (2.5)
a (2.5)
b (2.5)
b (20)
c (20)
b (2.5)
b (2.5)
D
C
C
C
D
D
C
C
2 h, room temp. TEA[e] (20)
–
–
–
16
–
–
35
8
21
–
–
–
12
4
34
68
92
90
7
[
f]
5 d, 60 °C
5 d, 60 °C
5 d, 60 °C
TEA (0.1)
DABCO (0.1)
TEA (0.1)
2 h, room temp. TEA (20)
2 h, room temp. TEA (20)
5 d, 60 °C
5 d, 60 °C
DABCO (0.1)
DABCO (1)
29
15
–
–
8
[
a] Equivalents with respect to [60]fullerene. [b] C: 1-chloronaphthalene, D: chlorobenzene. [c] Recovered by chromatography. [d] The
[28]
experiment described previously by Ohno et al.
was repeated in our laboratory and gave similar results. [e] TEA: triethylamine. [f]
More 60[fullerene] was recovered in mixture with 1-chloronaphthalene.
Suggested Mechanism
The overall reactivity of [60]fullerene with primary nitro
compounds in 1-chloronaphthalene is illustrated in
Scheme 2, in addition to the model reaction of methyl
acrylate in the same solvent (these are consistent with the
known behaviour in chloroform).[
21,23,29]
The results of these reactions are strongly dependent
upon the nature of the nitro compound and the amount of
base employed (whether excess or catalytic). Ethyl nitro-
acetate (1b) underwent condensation with [60]fullerene un-
der base catalysis in the same manner as with methyl acry-
II
late, although in the latter case addition of Cu salt was
required to favour condensation over addition (see Table 2,
entry 13). No addition product analogous to 3 has been evi-
denced with [60]fullerene under base catalysis (with or with-
Scheme 3. Plausible reaction mechanism.
II
out Cu ) nor in excess base. On the other hand, addition
products of this kind (6, Scheme 3) have been claimed as
intermediates in the reaction of nitroethane (and other
The conversion of the adduct 6 into oxime 5 is explained
nitroalkanes, but not ethyl nitroacetate) with [60]fullerene through the formation of several intermediates, for which
[
28]
in excess base, leading to the oxime 5.
evidence is lacking. In our opinion, the cycloaddition of
Scheme 2. Reactivity of electron-poor alkenes and [60]fullerene with primary nitro compounds.
4
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Reactivity of [60]Fullerene with Primary Nitro Compounds
nitronic acid to [60]fullerene to give the unstable intermedi- spectrometer (Thermo, San Jose, CA, USA) equipped with a con-
ventional ESI source (negative polarity). IR spectra were recorded
with a Perkin–Elmer 881 spectrophotometer. Elemental analyses
were carried out with a Perkin–Elmer 240C Elemental Analyser
apparatus. All compounds were named by using Autonom® (Be-
ilstein Information Systems) and modified as appropriate. Com-
mercially available (Lancaster and Aldrich) nitroethane (1a),
methyl nitroacetate, ethyl nitroacetate (1b), benzoylnitromethane
ate adduct 7 (Scheme 3) accounts for both results: de-
hydration to 4 in acid medium[38] and isomerisation of 7 to
the oxime 5 in excess base. Activated nitro compounds such
as ethyl nitroacetate are unable to produce the intermediate
cycloadduct 7 in excess base because they mainly exist as
the conjugated base (nitronate), the amount of the nitronic
acid being too low for appreciable cycloaddition.
(
1e), organic bases, 99% HNO
3
(density 1.52), 1-chloronaphthalene
(
technical grade, 1.192 g/mL at 20 °C), acrylamide (solubility: in
[39]
chloroform 2.66 g/100 mL,
slightly soluble in toluene and 1-
Conclusions
chloronaphthalene), methyl acrylate and fullerene were used as
supplied. CHCl (ethanol-free) was filtered through a short pad of
potassium carbonate just before use. Chloroacetone was distilled
before use. Toluene was distilled from CaH before use. Copper(II)
acetate and copper powder were used as supplied. N-Methyl-
3
Model reactions of ethyl nitroacetate (1b) with electron-
poor dipolarophiles are scarcely affected by the solvent em-
ployed (Tables 1 and 2). Thus, reactions of [60]fullerene
2
with several “activated” primary nitro compounds were car- nitroacetamide (1c) was prepared following a previously reported
ried out in 1-chloronaphthalene, in which [60]fullerene has procedure from ethyl nitroacetate (1b).[32] tert-Butyl (2-amino-
ethyl)carbamate was prepared in 70% yield following a previously
the highest solubility (0.071 m). Base-catalysed condensa-
tion to [60]fulleroisoxazolines (4) was the predominant re-
action (Table 3), giving moderate yields of the products
even with only base as catalyst.
reported procedure[ starting from ethylenediamine; 1H NMR
40]
(
2
200 MHz, CDCl
H, CH NH ), 3.26 (q, J = 6.0 Hz, 2 H, CH
H, CONH) ppm; CH NH protons were not detected. Diethyl (2-
oxopropyl)phosphonate was prepared in 36% yield as a pale-yellow
3
): δ = 1.41 [s, 9 H, C(CH
3
)
3
], 2.76 (t, J = 6.2 Hz,
2
2
2
NH), 4.94 (br. s, 1
2
2
However, nitroethane did not undergo a similar conden-
sation, but was converted into oxime 5a, particularly in ex-
cess base, as has previously been reported[ (Table 4). The
synthesis of [60]fulleroisoxazolines 4 offers a valid alterna-
[41]
liquid following a previously reported procedure
starting from
28]
chloroacetone and triethyl phosphite (Michaelis–Arbuzov reac-
[42,43] 1
tion);
3
H NMR (200 MHz, CDCl ): δ = 1.30 (t, J = 14.4 Hz,
tive to the use of unfriendly chloroximes as nitrile oxide 6 H, 2 CH CH O), 2.28 (s, 3 H, CH CO), 3.04 [d, J(H,P) =
3
2
3
precursors.
23.2 Hz, 2 H, CH
2
P], 4.04–4.22 (m, 4 H, 2 CH
3
CH
2
O) ppm. Acetyl
(d = 1.52;
.713 g, 11.33 mmol) and acetic anhydride (1.157 g, 11.33 mmol) at
nitrate (AcONO
2
) was prepared by mixing 99% HNO
3
0
–
4
10 to –5 °C and keeping, whilst stirring, the mixture at –7 °C for
Experimental Section
h.[
44]
General Methods and Materials: Melting points were determined
in capillary tubes with a Büchi 510 apparatus. Chromatographic
separations were performed on silica gel 60 (40–6.3 μm) with ana-
Model Reactions with DABCO as Catalyst: (Table 1) The spectro-
scopic yields reported in Table 1 refer to reactions performed in a
homemade apparatus in which several reactions were carried out
simultaneously under controlled stirring and temperature. A mix-
ture of ethyl nitroacetate (1b, 1.06 mmol), DABCO (4.8 mg,
f
lytical-grade solvents, driven by a positive pressure of air; R values
refer to TLC (visualised with UV light and/or by dipping the plates
into a solution of permanganate or anisaldehyde followed by heat-
ing with a heat gun) carried out on alumina-backed plates coated
with 25-mm silica gel (Merck F254). Solvents were removed by
evaporation on a rotavap at room temperature, except for 1-chloro-
0.0424 mmol), methyl acrylate or acrylamide (0.424 mmol) and di-
methyl sulfone (5–10 mg) in the indicated solvent (1.4 mL) was kept
at 60 °C. After 24 h the reaction mixture was concentrated under
1
1
13
reduced pressure and the H NMR spectrum (CDCl
3
) recorded
naphthalene, which was removed by chromatography. H and
C
(
except with 1-chloronaphthalene, for which a portion was with-
drawn from the reaction mixture and diluted with 0.6 mL of
CDCl ). Integration of the CH proton signals of the internal stan-
NMR spectra were recorded with a Varian Mercuryplus 400 spec-
1
13
trometer (operating at 400 MHz for H and 100.58 MHz for C)
unless otherwise stated. 31P NMR spectra were recorded with a
3
3
1
dard (s, 2.93 ppm) and the more reliable signals of 2 and 3 gave the
spectroscopic yield. Table 1, entries 1–3: integration of methylenic
Bruker spectrometer (operating at 162 MHz). The H NMR spec-
troscopic data are reported as [multiplicity, coupling constant(s) in
Hz, integration]; the multiplicity is denoted by s = singlet, d =
2
protons for 3b (R = CONH
2
; m, 2.50–2.38 ppm) and 4-H protons
2
for 2b (R = CONH
methyl protons for 3b (R = CO
CO CH ; s, 3.78 ppm). In the case of an unclear result, a duplicate
2
; dd, 3.33 ppm); entries 4–6: integration of
doublet, t = triplet, m = multiplet or unresolved, br. = broad signal.
2
2
The multiplicities of the 13C NMR signals (s, d, t, q; for compounds
2
3
CH ; s, 3.65 ppm) and 2b (R =
2
3
1f and 4f, the multiplicity for C–H are reported along with C–P
experiment was performed.
coupling constants) and the assignments were determined by means
of gHSQC and gHMBC experiments. Chemical shifts were deter-
II
Model Reactions with Cu /NMP as Catalyst in Various Solvents:
mined relative to the residual solvent peak (CHCl
3
: 7.24 ppm for
H NMR and 77.0 ppm for C NMR). P NMR chemical shifts
are given relative to H PO (δ = 0 ppm) as external reference. ESI
electronspray ionisation) mass spectra were recorded (infusing the
(Table 2) The spectroscopic yields reported in Table 2 refer to reac-
tions performed as above. A mixture of nitro compound (1a, 1b or
1c, 1.06 mmol), NMP (entries 1–6: 21.0 mg, 0.212 mmol; entries 7–
1
13
31
3
4
(
2
15: 4.2 mg, 0.0424 mmol), Cu(OAc) (3.85 mg, 0.021 mmol),
sample solution directly into the ESI chamber by syringe pump)
with a ThermoFisher LCQ-Fleet ion-trap instrument and spectra
were recorded by using either ESI or ESI techniques. Ion mass/
charge (m/z) ratios are reported as values in atomic mass units fol-
lowed by the intensities relative to the base peak in parentheses.
HRMS was performed with an LTQ-Orbitrap high-resolution mass
methyl acrylate or acrylamide (0.424 mmol) and dimethyl sulfone
(5–10 mg) in the indicated solvent (1.4 mL) was kept at 60 °C
(80 °C for entries 14 and 15). After 24 h the reaction mixture was
+
–
concentrated under reduced pressure (except for 1-chloronaphthal-
1
ene, see above) and the H NMR spectrum (CDCl
3
, D
2
O for en-
try 14) recorded. For entry 14, the reaction mixture was extracted
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O42990
/KAP1
Date: 28-10-14 18:16:01
Pages: 11
G. Biagiotti, S. Cicchi, F. De Sarlo, F. Machetti
FULL PAPER
1
with D
Integration of the CH
.93 ppm) and the more reliable signals of 2 and 3 gave the spectro-
scopic yield. Table 2, entries 1–6: integration of 5-H proton of 2a
2
O (3ϫ 1 mL) and the H NMR spectrum (D
2
O) recorded. found C 43.70, H 6.71, N 16.25. tert-Butyl-(2-aminoethyl)carb-
3
proton signals of the internal standard (s,
amate was recovered (1.015 g, 50% of the excess used) as reported
above. The spectroscopic data are identical for the three samples.
2
Diethyl (Nitromethyl)phosphonate (1f): Diethyl (nitromethyl)phos-
phonate (1f) was prepared by slight modifications of reported pro-
2
2
(R
= CO
2 2
Me; dd, 4.98 ppm; R = CONH ; dd, 4.96 ppm); no
[45]
or bis-adducts[46] were observed. En-
signals of the adducts
cedures.[
34,35]
A 25 mL two-necked round-bottomed flask equipped
2
tries 7–10: integration of methylenic protons for 3b (R = CONH
2
;
with a thermometer was charged with diethyl (2-oxopropyl)phos-
phonate (2.0 g, 10.3 mmol) and acetic anhydride (1.073 g). At an
internal temperature of 32 °C, freshly prepared (stored in an ice-
m, 2.50–2.38 ppm) and 4-H protons for 2b (R2 = CONH
; dd,
2
2
3.33 ppm). Entries 11–13: integration of methyl protons for 3b (R
2
=
2
CO CH
3
; s, 3.65 ppm) and 2b (R = CO
2
CH
3
; s, 3.78 ppm). En-
; dd, 3.52 ppm).
2
bath) acetyl nitrate (AcONO ) was added dropwise carefully keep-
2
try 14: integration of 4-H for 2c (R = CO
2
CH
3
2
ing the temperature below 35 °C. After 1 h at room temperature,
water was added (6 mL) and after a further 1 h the reaction mixture
was extracted with diethyl ether (5ϫ 8 mL). The combined organic
Entry 15: integration of the 4-H proton for 2c (R = CONH
.46 ppm).
2
; dd,
3
phases were dried with Na
duced pressure and the residue purified by flash chromatography
silica gel, petroleum ether to petroleum ether/EtOAc = 1:2) to af-
ford 1f (R = 0.45, 841 mg, 42%) as a pale-yellow liquid (turned
2 4
SO , filtered, concentrated under re-
tert-Butyl [2-(2-Nitroacetamido)ethyl]carbamate (1d): At 80 °C in a
slight excess of amine: tert-Butyl (2-aminoethyl)carbamate (1.61 g,
(
10.08 mmol) was added to a mixture of methyl nitroacetate
(8.4 mmol, 0.625 mL), pyridine (1.05 mL) and water (1.05 mL) and
f
brown after standing for a few days). Eventually, traces of an un-
known compound were removed by dissolving the crude material
in 0.1 m NaOH (30 mL) and washing with chloroform (2ϫ 20 mL).
Subsequent acidification of the aqueous solution with 10% HCl
the reaction mixture stirred at 80 °C in a sealed tube. After 3 h
the reaction mixture was cooled and concentrated under reduced
pressure. The residue was dissolved in water, cooled and the solu-
tion acidified to pH 4 with 3 n HCl. The solution (about 20 mL)
(
to pH 3) and extraction with chloroform (3ϫ 20 mL) gave, after
drying with Na SO and concentration at reduced pressure, pure
f. H NMR (CDCl , 400 MHz): δ = 1.36 (t, J = 7.0 Hz, 6 H,
CH CH ), 4.19–4.27 (m, 4 H, CH
5.4 Hz, 2 H, CH
was then extracted with CHCl
phases were dried with Na SO
reduced pressure. The residue was subjected to flash column
chromatography on silica gel (petroleum ether/AcOEt = 1:2, R
3
(5ϫ 18 mL). The combined organic
2
4
, filtered and concentrated under
2
4
1
1
3
2
CH
2
), 4.90 [d, J(H,P) =
, 100 MHz): δ = 16.2
f
=
3
2
3
1
3
1
2
P] ppm. C NMR (CDCl
3
0
1
.31) to yield pure 1d (315 mg, 14%) as a yellowish powder, m.p.
3
2
1
[q, J(C,P) = 5.4 Hz, CH ], 64.3 (t, J
= 6.9 Hz, CH O), 72.1 [t,
15–116 °C. H NMR (400 MHz, CDCl
NH), 3.44 (m, 2 H, CH
) ppm. 1 C NMR (100.58 MHz, CD
OD): δ = 28.3 [q, 3
], 41.4 (t, CH NH), 41.7 (t, CH NH), 79.6 (residual
), 81.1 [s, C(CH ], 159.4 [s, NHCOC(CH ], 160.7 (s,
CONH) ppm. 1 C NMR (100.58 MHz, CDCl
, sparingly soluble):
δ = 29.6 [q, 3 C, C(CH ], 39.6 (t, CH NH), 41.8, (t, CH NH),
7.9, (t, CH NO ), 80.3, [s, C(CH ], 160.7 (s, CO) ppm;
NHCOOC(CH carbon not detected. IR (KBr): ν˜ = 3354 (w) [N–
H], 3457 (w) [N–H], 2977 (w) [C–H], 1672 (s) [C=O], 1566 (s), 1546
3
): δ = 1.46 [s, 9 H, C(CH
3
)
3
C-P
2
1
31
J(C,P)
=
141.9 Hz, CH
2
NO
2
] ppm.
P
3
NMR (CDCl ,
3
], 3.34 (m, 2 H, CH
2
2
NH), 5.1 (s, 2 H,
[47]
3
3
˜
80.95 MHz): δ = 9.24 ppm. IR (CDCl ): ν = 2985 (w), 1557 (s)
CH
C, C(CH
CDHNO
2
NO
2
3
[
(
2 2
NO ], 1370 (w) [NO ], 1274 (m) [P=O], 1167 (w), 1062 (m), 1025
s) cm . MS (ESI ): m/z = 196 [M – 1] . C H12NO P (197.13):
5 5
3
)
3
2
2
–
1
–
–
2
3
)
3
3 3
)
3
calcd. C 30.46, H 6.14, N 7.11; found C 30.41, H 5.96, N 6.72.
3
3
)
3
2
2
General Procedure for the Reactions of Nitro Compounds 1a–f with
7
2
2
3 3
)
[
1
60]Fullerene: (Table 3) 1-Chloronaphthalene (1 mL, but 1.4 mL for
c) was added to fullerene (50 mg, 0.069 mmol, 1 equiv.), nitro
compound 1a–f (0.173 mmol, 2.5 equiv.), copper acetate (0.6 mg,
3 3
)
(
(
s) [NO
m), 1255 (m), 1166 (m) cm . MS (ESI ): m/z = 246 [M – 1] .
(247.25): calcd. C 43.72, H 6.93, N 17.00; found C
3.36, H 7.36, N 17.07.
2
], 1508 (s), 1448 (w), 1384 (w), 1367 (w), 1340 (w), 1282
0
0
.00345 mmol, 0.05 equiv.) and N-methylpiperidine (0.7 mg,
.9 μL, 0.0069 mmol, 0.1 equiv.). Then the mixture was maintained
–1
–
–
9 17 3 5
C H N O
4
at 60 °C (but 80 °C for 1c and 1d) for 5 d whilst stirring in a sealed
tube.
At room temperature with an excess of amine: Methyl nitroacetate
Reaction of Nitroethane (1a) with [60]Fullerene to Give Isoxazolino-
(
(
0.905 g, 7.60 mmol) was added to an ice-cold solution of tert-butyl
2-aminoethyl)carbamate (4.870 g, 30.4 mmol) in MeOH (9 mL).
[
(
0
R
60]fullerene 4a and Oxime 5a: TLC analysis of the brown mixture
eluent toluene) showed the presence of unreacted fullerene (R
.98), 1-chloronaphthalene (R = 0.92, UV-detected), and spots at
= 0.66 and R = 0. The crude reaction mixture was loaded di-
f
=
The clear reaction mixture was stirred at room temperature for 3 d
and then concentrated under reduced pressure. The residue was
dissolved in water (8 mL) and the resulting solution (ice-cooled)
was acidified to pH 4 with 3 n HCl. The solution (about 50 mL)
f
f
f
rectly onto the top of a column of silica gel (3ϫ10 cm).
Chromatography (gradient petroleum ether to toluene then tolu-
ene/AcOEt) conducted under a slight pressure of air provided
was then extracted with CHCl
3
(5ϫ 50 mL). The combined organic
, filtered and concentrated under
phases were dried with Na SO
2
4
f
fulleroisoxazoline 4a (less than 1 mg, R = 0.66 toluene as eluent)
reduced pressure to give crude 1d (1.545 g) containing residual
methyl nitroacetate. The crude product was further purified by
washing with hexane to yield pure 1d (1.459 g, 78%) as a white
and fractions containing the adduct 5a (2.9 mg, see below for spec-
troscopic data) and analogous polyadducts {bis-adducts: 6.2 mg;
–
–
–
MS (ESI ): m/z = 869 [M – 1] ; tris-adducts: 16.2 mg; MS (ESI ):
powder, m.p. 114–115 °C. C
9
H
17
N
3
O
5
(247.25): calcd. C 43.72, H
–
m/z = 944 [M – 1] }. Due to the meagre amount obtained, com-
pound 4a was only partially characterised. 4a: H NMR (400 MHz,
): δ = 2.73 (s, CH
M] . Attempted reactions with more copper acetate or copper
6.93, N 17.00; found C 43.36, H 7.30, N 17.22. tert-Butyl (2-amino-
1
ethyl)carbamate was recovered (1.09 g, 30% of the excess used) by
extraction of the aqueous solution at pH 11 (ice-cooled solution
[14a]
–
CDCl
[
3
3
) ppm.
MS (ESI ): m/z (%) = 777 (100)
–
added with 3 n NaOH) with CH
2 2
Cl (5ϫ 50 mL).
powder instead of copper acetate, less base (0.1 equiv.) or in chloro-
form did not afford a higher yield of fulleroisoxazoline 4a.
The crude product obtained by the same procedure from the ester
(0.50 g, 4.2 mmol) and the amine (2.69 g, 16.8 mmol), purified by
Reaction of Ethyl Nitroacetate (1b) with [60]Fullerene to Give Isox-
flash chromatography on silica gel (petroleum ether/AcOEt = 1:2,
azolino[60]fullerene 4b: TLC analysis of the brown reaction mixture
R
f
= 0.31), yielded pure 1d (336 mg, 32%) as a white powder, m.p. (eluent toluene) showed the presence of unreacted fullerene (R
f
=
1
20–121 °C. C (247.25): calcd. C 43.72, H 6.93, N 17.00; 0.98), 1-chloronaphthalene (R = 0.92, UV-detected) and [60]-
9
H
17
N
3
O
5
f
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42990
/KAP1
Date: 28-10-14 18:16:01
Pages: 11
Reactivity of [60]Fullerene with Primary Nitro Compounds
fullero-3-ethoxycarbonylisoxazoline (4b) (R = 0.78). The crude re-
f
of the brown reaction mixture (eluent toluene) showed the presence
action mixture was loaded directly onto the top of a column of
silica gel (3ϫ10 cm). Chromatography (gradient petroleum ether
to toluene) conducted under a slight pressure of air provided reco-
vered 1-chloronaphthalene (880 mg, 74%), [60]fullerene (19.9 mg,
of unreacted fullerene (R
0.92, UV-detected) along with a spot at R
analysis (eluent toluene/AcOEt = 3:1) showed the presence of [60]
fulleroisoxazoline 4d (R = 0.60). The crude reaction mixture was
f
= 0.98) and 1-chloronaphthalene (R
f
=
f
= 0. Subsequent TLC
f
4
0% recovered) and 4b (after washing with pentane, 18.1 mg, dark-
loaded directly onto the top of a column of silica gel (3ϫ10 cm).
Chromatography (gradient petroleum ether to toluene then toluene
to AcOEt) conducted under a slight pressure of air provided reco-
vered 1-chloronaphthalene (890 mg, 74%), C60 (22 mg) and pure
4d (after washing with hexane, as a dark brown-powder, 20.8 mg,
brown powder, 31%). The yield based on consumed [60]fullerene
was 52%. The same reaction repeated with more NMP (3.8 mg,
0
3
1
CH
(
.5 equiv.) gave a lower yield of isoxazoline 4b (14.5 mg, 25%) and
1
0.6 mg of recovered C60. 4b: H NMR (400 MHz, CDCl
.49 (t, J = 7.4 Hz, 3 H, CH CH ), 4.57 (q, J = 7.4 Hz, 2 H,
CH + 0.02 m [Cr-
) ppm. 13C NMR (100.58 MHz, CDCl
acac) ]): δ = 14.2 (CH CH ), 63.0 (CH CH
3
): δ =
3
2
28%; the yield based on unrecovered fullerene C60 was 50%). 4d:
1
3
2
3
H NMR (400 MHz, CDCl
3
): δ = 1.51 [s, 9 H, (CH
NH), 4.90 (br. s, 1 H,
NH), 7.73 (br. s, 1 H, NH) ppm. C NMR (100.58 MHz, CDCl
with 0.02 m [Cr(acac) ], 102400 transients): δ = 28.22 (q, 3 C, 3
CH ), 39.81 (br. t, CH NH), 40.95 (t, CH NH), 75.8 (isoxazoline-
C-4), 80.1 [C(CH ], 105.5 (isoxazoline-C-5), 136.2, 137.0, 140.1,
3 3
) C], 3.42–3.50
3
3
2
3
2
), 76.6 (isoxazoline-C- (m, 2 H, CH
2
NH), 3.60–3.66 (m, 2 H. CH
2
1
3
4
1
1
1
), 106.2 (isoxazoline-C-5), 136.5, 137.0, 140.2, 141.7, 141.8, 142.1,
42.3, 142.4, 142.8, 142.9, 143.0, 143.5, 144.1, 144.2, 144.5, 145.1,
45.2, 145.3, 145.7, 146.0, 146.2, 146.3, 146.4, 146.8, 147.2, 147.3,
47.8, 159.8 ppm. IR (KBr): ν˜ = 2973 (w), 2951 (w), 2920 (w), 1720
3
3
3
2
2
3 3
)
(
(
C
(
1
s) [C=O], 1584 (w) [C=N], 1329 (m), 1174 (s) [C60], 1138 (s), 526 140.3, 141.7, 141.8, 142.1, 142.3, 142.4, 142.5, 142.6, 142.7, 142.8,
–1
–
–
–
s) [C60] cm . MS (ESI ): m/z = 835 [M] . HMRS (ESI ): calcd. for
144.0, 144.1, 144.2, 144.5, 145.1, 145.3, 145.6, 145.9, 146.0, 146.2,
146.3, 147.1, 147.8, 148.3, 159.4 ppm. IR (KBr): ν˜ = 3383 (m) [N–
H], 3326 (m) [N–H], 2923 (m) [C–H], 1688 (s) [C=O], 1594 (w)
[C=N], 1533 (m), 1443 (w), 1363 (w), 1272 (m), 1167 (m) 526
–
64
H
5
NO
835.73): calcd. C 91.98, H 0.46, N 1.68; found C 91.60, H 0.49, N
.60.
3 5 3
[M] 835.0269; found 835.0268 (Ϯ0.0001). C64H NO
–
1
–
–
–
(
m) cm . MS (ESI ): m/z (%) = 949 (100) [M] . HMRS (ESI ):
Reaction to Give 4b in the Presence of NMP/[Cu] as Catalyst in
Toluene: Toluene (1.4 mL) was added to [60]fullerene (50 mg,
–
calcd. for C69
15 3 2
H N O 949.1063 [M] ; found 949.1054 (Ϯ0.0001).
0
0
0
0
.069 mmol, 1 equiv.), ethyl nitroacetate (23 mg, 19 μL,
.173 mmol, 2.5 equiv.), copper acetate (0.6 mg, 0.00345 mmol, Isoxazolino[60]fullerene 4e: TLC analysis of the brown reaction
.05 equiv.) and N-methylpiperidine (0.7 mg, 0.9 μL, 0.0069 mmol,
Reaction of Benzoylnitromethane (1e) with [60]Fullerene to Yield
mixture (eluent toluene) showed the presence of unreacted fullerene
.1 equiv.), and then the mixture was maintained at 60 °C for 5 d
(R = 0.98), 1-chloronaphthalene (R = 0.92, UV-detected), [60]-
f
f
whilst stirring in a sealed tube. TLC analysis of the brown mixture
eluent toluene) showed the presence of unreacted fullerene (R
.98) and isoxazoline 4b (R = 0.78). The crude reaction mixture
was loaded directly onto the top of a column of silica gel
3ϫ10 cm). Chromatography (gradient petroleum ether/toluene =
:1 to toluene) conducted under a slight pressure of air provided
60]fullerene (26 mg, 52% recovered) and fulleroisoxazoline 4b (af-
ter washing with pentane, 11 mg, dark-brown powder, 19%). The
yield based on consumed [60]fullerene was 39%. The spectroscopic
and analytical data of 4b are identical to those reported above.
f f
fullero-3-benzoylisoxazoline (4e) at R = 0.84 and byproducts at R
(
0
f
=
= 0.54 and 0.28. The crude reaction mixture was loaded directly
onto the top of a column of silica gel (3ϫ10 cm). Chromatography
(gradient petroleum ether to toluene) conducted under a slight
pressure of air provided[ recovered 1-chloronaphthalene (940 mg,
78%), recovered C60 (19.7 mg) and fulleroisoxazoline 4e (black-
brown powder, 22.6 mg, 38%; the yield based on consumed fuller-
f
48]
(
2
[
1
ene C60 was 46%). 4e: H NMR (400 MHz, CDCl ): δ = 7.60–7.66
3
(m, 2 H, Ph-Hmeta), 7.70–7.79 (m, 1 H, Ph-Hpara), 8.46–8.52 (d, 2
H, Ph-Hortho) ppm. 1 C NMR {100.58 MHz, CDCl3 with 0.02 m
3
3
Reaction of N-Methylnitroacetamide (1c) with [60]Fullerene to Yield [Cr(acac) ]}: δ = 81.82 (isoxazoline-C-4), 105.4 (isoxazoline-C-5),
Isoxazolino[60]fullerene 4c: TLC analysis of the brown reaction
mixture (eluent toluene) showed the presence of unreacted fullerene
128.6 (Ph-C), 130.6 (Ph-C), 134.4 (Ph-C), 136.0 (Ph-C), 136.1,
137.1, 140.2, 141.7, 142.1, 142.3, 142.4, 142.5, 142.6, 142.7, 142.8,
143.0, 144.1, 144.2, 144.6, 145.1, 145.3, 145.6, 145.9, 146.1, 146.2,
146.3, 146.9, 147.1, 147.7, 151.5 (isoxazoline-C-3), 185.6
(COPh) ppm. IR (KBr): ν˜ = 3040 (w), 2921 (m), 2851 (m), 1647 (s)
[C=O], 1574 (m), 1446 (m), 1324 (m), 1261 (m), 1166 (m), 1090
(w), 1064 (w), 1010 (m), 981 (w), 920 (m), 842 (s), 800 (w), 753 (m),
(
=
R
f
= 0.98), 1-chloronaphthalene (R
0.22) and an additional spot at R
ture was loaded directly onto the top of a column of silica gel
3ϫ10 cm). Chromatography (gradient petroleum ether to toluene
f
= 0.92, UV-detected), 4c (R
= 0. The crude reaction mix-
f
f
(
then toluene/AcOEt = 10:1 for the tail) conducted under a slight
pressure of air provided recovered 1-chloronaphthalene (1.34 g,
8
–
1
–
668 (m), 562 (m) [C60], 523 (s) [C60] cm . MS (ESI ): m/z (%) =
–
–
0%), C60 (18.2 mg, 36%) and fulleroisoxazoline 4c (23.8 mg, 42%; 867 (100) [M] . HMRS (ESI ): calcd. for C68H NO 867.0320
5 2
–
the yield based on consumed [60]fullerene was 66%) along with
[M] ; found 867.0316 (Ϯ 0.0001).
traces of the 2:1 cycloadduct (R
f
= 0.2, eluent toluene/AcOEt =
Reaction of Diethyl (Nitromethyl)phosphonate (1f) with [60]Fullerene
to Yield Isoxazolino[60]fullerene 4f: TLC analysis of the brown reac-
tion mixture (toluene) showed the presence of unreacted fullerene
10:1). The latter compound was obtained only in traces and hence
–
–
1
was not fully characterised: MS (ESI ): m/z (%) = 919 [M] . 4c: H
NMR (CDCl ): δ = 3.11 (d, J = 4.8 MHz, 3 H, CH NH) ppm.
3C NMR (100.58 MHz, CDCl
with 0.02 m [Cr(acac) ]): δ = 29.7
CH NH), 136.0, 136.8, 139.8, 140.0, 141.4, 141.5, 141.8, 141.9,
3
3
(
R
= 0.98), 1-chloronaphthalene (R
spot at R = 0. Subsequent TLC analysis (eluent toluene/AcOEt =
:1) showed the presence of fulleroisoxazoline 4f (R = 0.57). The
f
= 0.92, UV-detected), and a
f
1
3
3
f
(
3
4
f
1
1
42.1, 142.2, 142.3, 142.4, 142.5, 143.7, 143.8, 143.9, 144.2, 144.8,
45.0, 145.3, 145.5, 145.6, 145.9, 146.0, 146.9, 147.4, 148.3 ppm.
crude reaction mixture was loaded directly onto the top of a col-
umn of silica gel (3ϫ10 cm). Chromatography (gradient hexane to
toluene then toluene to AcOEt) conducted under a slight pressure
of air provided recovered 1-chloronaphthalene (900 mg, 76%), C60
IR (KBr): ν˜ = 3371 (s) (N–H), 1726 (s) [C=O], 1597 (w) [C=N],
–
1
1
183 (m) [C60], 1121 (s), 579 (m) [C60], 526 (s) [C60] cm . MS
–
–
–
(ESI ): m/z (%) = 820 (100) [M] . HMRS (ESI ): calcd. for
(
29.4 mg, 58%) and 4f (dark powder, 13.7 mg, 22%; the yield based
–
C
63
H
3
N
2
O
2
819.0194 [M – H] ; found 819.0204 (Ϯ 0.0001).
1
on consumed fullerene C60 was 53%). 4f: H NMR (400 MHz,
CDCl
0.8 Hz, 6 H, 2 CH
3
4
Reaction of N-(tert-Butoxycarbonylaminoethyl)nitroacetamide (1d)
with [60]Fullerene to Yield Isoxazolino[60]fullerene 4d: TLC analysis
3
, * minor isomer): δ = 1.43 [td, J(H,H) = 7.2, J(H,P) =
CH
2
O], 1.48* [td, J(H,H) = 7.2, 4J(H,P) =
3
3
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O42990
/KAP1
Date: 28-10-14 18:16:01
Pages: 11
G. Biagiotti, S. Cicchi, F. De Sarlo, F. Machetti
FULL PAPER
0
.8 Hz, 6 H, 2 CH
3
CH
2
O], 4.43 (m, 4 H, 2 CH
with 0.02 m [Cr(acac)
mer): δ = 16.22 [d, J(C,P) = 7.0 Hz, CH CH O], 16.29* [d, J(C,P)
7.0 Hz, CH CH CH
O], 64.44 [d, 2J(C,P) = 6.0 Hz, CH
4.72* [d, 2J(C,P) = 6.0 Hz, CH O], 78.90 [d, 2J(C,P) =
CH
9.0 Hz, isoxazoline-C-4], 104.2 [d, J(C,P) = 6.0 Hz, isoxazoline-
3
CH
2
O) ppm. 13C Reactions of Ethyl Nitroacetate (1b): In 1-chloronaphthalene with
NMR (100.58 MHz, CDCl
3
3
], * minor iso-
triethylamine (0.1 equiv) at 60 °C (entry 4): TLC analysis of the
brown mixture (eluent toluene) showed the presence of unreacted
3
3
3
2
=
6
1
3
2
3
2 f f f
O], fullerene (R = 0.98), 1-chloronaphthalene (R = 0.92) and 4b (R
3
3
2
= 0.78). The crude reaction mixture was loaded directly onto the
top of a column of silica gel (3ϫ10 cm). Chromatography (gradient
hexane to toluene then toluene to AcOEt) conducted under a slight
pressure of air provided 1-chloronaphthalene (1.12 mg, 94% reco-
vered), C60 (34 mg, 68% recovered), isoxazoline 4b after washing
with pentane and a dark-brown powder (9.4 mg, 16%). The yield
C-5], 136.1, 136.8, 140.1, 140.3, 141.7, 141.8, 142.1, 142.2, 142.3,
142.5, 142.7, 142.8, 142.9, 143.9, 144.0, 144.1, 144.6, 145.1, 145.2,
1
45.6, 145.8, 145.9, 146.0, 146.2, 146.3, 147.1, 147.7, 149.3 [d,
1
31
J(C,P) = 213.0 Hz, isoxazoline-C-3] ppm. P NMR (121.4 MHz,
CDCl
3
, * minor isomer): δ = 2.14, 1.32* ppm. IR (KBr): ν˜ = 2907 based on consumed [60]fullerene was 48%. The spectroscopic and
(
5
w), 1619 (w) [C=N], 1429 (w), 1270 (m) [P=O], 1020 (s), 611 (w), analytical data of 4b are as reported above.
–1
–
–
26 (m) [C60] cm . MS (ESI ): m/z (%) = 899 [M] (100). HMRS
In chlorobenzene with excess of triethylamine at room temp. (en-
try 5): TLC analysis of the brown mixture (eluent toluene) showed
–
–
4
(ESI ): calcd. for C65H10NO P 899.0348 [M] ; found 899.0349
(
Ϯ 0.0001).
the presence of unreacted fullerene (R = 0.98), 1-chloronaphthal-
f
ene (R = 0.92) and the 1b·N(Et ) salt (R = 0). Solvent removal and
f
f
3
General Procedure for the Reactions of Nitro Compounds 1 with
60]Fullerene and Base Under Various Conditions: (Table 4) The
chromatography conducted under a slight pressure of air (gradient
[
petroleum ether to toluene) gave recovered C60 (9.2 mg, 92%). MS
solvent was added to [60]fullerene (50 mg, 0.069 mmol in 1 mL 1-
chloronaphthalene or 10 mg, 0.014 mmol in 2 mL chlorobenzene
or 10 mL of chlorobenzene for entry 1), nitro compound and base
–
(
ESI ) analysis of the crude reaction mixture showed the presence
–
of 1b (m/z = 132 [M – 1] ).
(as indicated in Table 4) and maintained under the conditions indi-
In 1-chloronaphthalene with DABCO (0.1 equiv) at 60 °C (entry 7):
cated whilst stirring in a sealed tube.
The same work-up reported above for the preparation of 4b
(
C
Table 3) provided 1-chloronaphthalene (904 mg, 76% recovered),
60 (3.6 mg, 7% recovered) and isoxazoline 4b (after washing with
Reactions of Nitroethane (1a): In chlorobenzene with excess trieth-
ylamine at room temp. (entry 1): The product 5a was evidenced in
the brown reaction mixture by TLC (eluent toluene/AcOEt = 1:1,
R = 0.90). Solvent removal and chromatography conducted under
f
a slight pressure of air (eluent toluene then toluene to AcOEt) gave
pentane, 16.8 mg, 29% as a dark-brown powder; the yield based on
consumed [60]fullerene was 31%). The spectroscopic and analytical
data of 4b are identical to those reported above.
In 1-chloronaphthalene with stoichiometric DABCO at 60 °C (en-
try 8): The same work-up reported above for the preparation of 4b
recovered C60 (5.6 mg, 12%), monoadduct oxime 5a (19 mg, 35%)
–
and polyadducts including a bis-adduct: 15.4 mg; MS (ESI ): m/z
(
C
Table 3) provided 1-chloronaphthalene (890 mg, 75% recovered),
60 (3.8 mg, 8% recovered), isoxazoline 4b (after washing with
–
1
=
869 [M – 1] . 5a: H NMR (CS
δ = 2.83 (s, 3 H, CH ), 6.48 (s, 1 H, OH), 7.32 (s, 1 H, OH) ppm;
on treatment with D O, the singlets at 6.48 and 7.32 ppm disap-
2 6
/[D ]acetone = 3:2, 100.6 MHz):
3
pentane, 8.7 mg, 15% as a dark-brown powder; the yield based on
consumed [60]fullerene was 26%). The spectroscopic and analytical
data of 4b are identical to those reported above.
2
–
–
peared. MS (ESI ): m/z = 794 [M – 1] . IR (KBr): ν˜ = 3389 (br.,
m), 2907 (s), 2840 (m), 1625 (w) [C=N], 1546 (w), 1423 (m), 1374
Reaction of N-Methylnitroacetamide (1c): In chlorobenzene with
excess of triethylamine at room temp. (entry 6): TLC analysis of the
brown mixture (eluent toluene) showed the presence of unreacted
(
5
m, w), 1264 (s), 1104 (w), 1040 (m), 1028 (m), 887 (m), 727 (m),
28 (s) [C60] cm . The above reaction has been previously reported
–1
(with partial experimental details) to give 46% yield of the oxime
[
28]
fullerene (R = 0.98), 1-chloronaphthalene (R = 0.92) and the
5
a.
f
f
1c·N(Et
3
) salt (R
f
= 0). Solvent removal and chromatography con-
In 1-chloronaphthalene with triethylamine (0.1 equiv) at 60 °C (en-
try 2): TLC analysis of the brown mixture (eluent toluene/AcOEt
ducted under a slight pressure of air (gradient petroleum ether to
toluene) gave recovered C60 (9.0 mg, 90%). MS (ESI) analysis of
the crude reaction mixture showed the presence of 1c (m/z = 117
=
5:1) showed the presence of unreacted fullerene (R
chloronaphthalene (R = 0.95, UV-detected) along with a spot at
= 0.66 (corresponding to oxime 5a) and a spot at R = 0 (corre-
f
= 1) and 1-
–
f
[M – 1] ).
R
f
f
Supporting Information (see footnote on the first page of this arti-
sponding to polyadducts analogous to 5). The crude reaction mix-
ture was loaded directly onto the top of a column of silica gel
cle): 1H and 13C NMR spectra of compounds 1d, 1f and 4b–4f,
31
and P NMR spectrum of 1f.
(3ϫ10 cm). Chromatography (hexane to toluene then toluene to
AcOEt as eluent) conducted under a slight pressure of air provided
recovered pure C60 (2 mg, 4%), a mixture of 1-chloronaphthalene Acknowledgments
and C60, monoadduct 5a (4.4 mg, 8%, spectroscopic data as above)
and polyadducts (24 mg). TLC analysis of the latter (AcOEt/
Dr. Elena Trogu is acknowledged for carrying out preliminary ex-
MeOH = 5:1) showed the presence of three close spots (UV-de- periments. The authors thank the Italian Ministero dell’Università
tected). MS (ESI) analysis of this fraction showed the presence of
bis-, tris- and tetrakis-adducts.
e della Ricerca (MIUR) (project: FIRB 2011 prot., grant number
RBAP11ETKA) and the Ente Cassa di Risparmio di Firenze for
financial support. Maurizio Passaponti (Università di Firenze) is
acknowledged for technical support.
In 1-chloronaphthalene with DABCO (0.1 equiv) at 60 °C (entry 3):
Work up as for entry 2 gave C60 (17.2 mg, 34%), 1-chloronaphthal-
ene (1.10 g, 92%), monoadduct 5a (11.1 mg, 21%, spectroscopic
data as above) and a mixture of polyadducts (11.3 mg). TLC analy-
sis of the latter (AcOEt/MeOH = 5:1) showed the presence of three
[
[
1] For its serendipitous discovery, see: H. W. Kroto, J. R. Heath,
S. C. O’Brien, R. F. Curl, R. E. Smalley, Nature 1985, 318, 162–
164.
–
different spots (UV-detected). MS (ESI ) analysis of this fraction
2] For its first-time production in isolable quantities (milligrams),
see:W. Krätschmer, L. D. Lamb, K. Fostiropoulos, D. R. Huff-
man, Nature 1990, 347, 354–358.
–
showed the presence of bis- (m/z = 869 [M – 1] ), tris- (m/z = 944
–
–
[
M – 1] ), and tetrakis-adducts (m/z = 1019 [M – 1] ).
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42990
/KAP1
Date: 28-10-14 18:16:01
Pages: 11
Reactivity of [60]Fullerene with Primary Nitro Compounds
[
[
3] For its preparation in macroscopic amounts (grams), see: a)
J. B. Howard, J. T. McKinnon, Y. Makarovsky, A. L. Lafleur,
M. E. Johnson, Nature 1991, 352, 139–141; b) J. B. Howard,
J. T. McKinnon, M. E. Johnson, Y. Makarovsky, A. L. Lafleur,
6248; d) H. Irngartinger, A. Weber, T. Escher, Eur. J. Org.
Chem. 2000, 1647–1651; e) T. Da Ros, M. Prato, J. Org. Chem.
2000, 65, 4289–4297.
[16] M. Ohno, A. Yashiro, S. Eguchi, Synlett 1996, 815–816.
J. Phys. Chem. 1992, 96, 6657–6662; c) K.-H. Homann, Angew. [17] For complete fullerene solubility in common and unusual sol-
Chem. Int. Ed. 1998, 37, 2434–2451; Angew. Chem. 1998, 110,
572.
vents, see: a) R. F. Ruoff, D. S. Tse, P. Malhotra, D. C. Lorents,
J. Phys. Chem. 1993, 97, 3379–3383; b) R. G. Makitra, R. E.
Pristanskii, R. I. Flyunt, J. Gen. Chem. 2003, 73, 1227–1232;
Zh. Obshch. Khim. 2003, 73, 1299–1304.
2
4] For the large-scale production of highly pure [60]fullerene (kil-
ograms), see: a) J.-F. Tremblay, Chem. Eng. News 2003, 81, 13–
14; b) K. Nagata, E. Dejima, Y. Kikuchi, M. Hashiguchi, Org. [18] J. K. Sørensen, J. Fock, A. H. Pedersen, A. B. Petersen, K. Jen-
Process Res. Dev. 2005, 9, 660–662; c) M. Hashiguchi, K. Na-
gata, K. Tanaka, Y. Matsuo, Org. Process Res. Dev. 2012, 16,
643–646.
num, K. Bechgaard, K. Kilsa, V. Geskin, J. Cornil, T.
Bjørnholm, M. Brøndsted Nielsen, J. Org. Chem. 2011, 76,
245–263.
[
5] For some pioneering works, see: a) T. Suzuki, Q. Li, K. C.
[19] The generation of nitrile oxide from nitro compounds has
rarely been reported, see, for example, ref.[
14a]
.
Khemani, F. Wudl, Ö. Almarsson, Science 1991, 254, 1186–
1
188; b) C. Bingel, Chem. Ber. 1993, 126, 1957–1959; c) M.
[20] H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int.
Ed. 2001, 40, 2004–2021; Angew. Chem. 2001, 113, 2056.
[21] a) L. Cecchi, F. De Sarlo, F. Machetti, Tetrahedron Lett. 2005,
46, 7877–7879; b) F. Machetti, L. Cecchi, E. Trogu, F.
De Sarlo, Eur. J. Org. Chem. 2007, 4352–4359.
[22] L. Cecchi, F. De Sarlo, F. Machetti, Synlett 2007, 2451–2453.
[23] L. Cecchi, F. De Sarlo, F. Machetti, Chem. Eur. J. 2008, 14,
7903–7912.
Maggini, G. Scorrano, M. Prato, J. Am. Chem. Soc. 1993, 115,
9798–9799.
[
6] For reactions that occur on the fullerene surface but are not
observed with standard alkenes, see, as examples: a) N. Martín,
M. Altable, S. Filippone, A. Martín-Domenech, R. Martínez-
Álvarez, M. Suarez, M. E. Plonska-Brzezinska, O. Lukoy-
anova, L. Echegoyen, J. Org. Chem. 2007, 72, 3840–3846; b)
W. Zhang, T. M. Swager, J. Am. Chem. Soc. 2007, 129, 7714– [24]
E. Trogu, C. Vinattieri, F. De Sarlo, F. Machetti, Chem. Eur. J.
012, 18, 2081–2093.
25] L. Guideri, F. De Sarlo, F. Machetti, Chem. Eur. J. 2013, 19,
65–677.
7
715; c) G.-W. Wang, X.-P. Chen, X. Cheng, Chem. Eur. J.
2
2006, 12, 7246–7253; d) T. Oshima, H. Kitamura, T. Higashi,
[
[
K. Kokubo, N. Seike, J. Org. Chem. 2006, 71, 2995–3000.
7] a) A. Hirsch, M. Brettreich, Fullerenes: Chemistry and Reac-
tions, Wiley-VCH, Weinheim, Germany, 2005; b) D. M. Guldi,
N. Martín (Eds.), Fullerenes: From Synthesis to Optoelectronic
Properties, Kluwer Academic Publishers, Dordrecht, The
Netherlands, 2002; c) R. Taylor, Lecture Notes on Fullerene
Chemistry: A Handbook for Chemists, Imperial College Press,
London, 1999.
6
[
26] F. De Sarlo, F. Machetti, Condensation of Primary Nitro Com-
pounds to Isoxazole Derivatives: Stoichiometric to Catalytic, in:
Methods and Applications of Cycloaddition Reactions in Organic
Syntheses (Ed.: N. Nishiwaki), Wiley, New York, 2014, p. 205–
222.
[
27] For recent applications, see: a) J. Chau, S. Xu, M. A. Ciufolini,
J. Org. Chem. 2013, 78, 11901–11910; b) S. F. Nielsen, D. R.
Greve, G. Grue-Sùerensen, C. Ryttersgaard, S. C. Shou, A. G.
Sams, WO2012 003829; Chem. Abstr. 2012, 156, 148477; c) D. J.
Parks, W. H. Parsons, R. W. Colburn, S. K. Meegalla, S. K.
Ballentine, C. R. Illig, N. L. Y. Qin, T. L. Hutchinson, M. L.
Lubin, D. Stone, J. F. Baker, C. R. Schneider, J. Ma, B. P. Dam-
iano, C. M. Flores, M. R. Player, J. Med. Chem. 2011, 54, 233–
[
8] a) D. M. Guldi, F. Zerbetto, V. Georgakilas, M. Prato, Acc.
Chem. Res. 2005, 38, 38–43; b) D. Bonifazi, O. Enger, F. Died-
erich, Chem. Soc. Rev. 2007, 36, 390–414; c) J. L. Delgado,
M. A. Herranz, N. Martín, J. Mater. Chem. 2008, 18, 1417–
1
426; d) B. C. Thompson, J. M. Fréchet, Angew. Chem. Int. Ed.
2008, 47, 58–77; Angew. Chem. 2008, 120, 62; e) D. M. Guldi,
B. M. Illescas, C. M. Atienza, M. Wielopolski, N. Martín,
Chem. Soc. Rev. 2009, 38, 1587–1597; f) A. M. López, A. Ma-
teo-Alonso, M. Prato, J. Mater. Chem. 2011, 21, 1305–1318.
9] See, for examples: a) ref.[ ; b) I. Guryanov, F. M. Toma, A.
Montellano López, M. Carraro, T. Da Ros, G. Angelini, E.
D’Aurizio, A. Fontana, M. Maggini, M. Prato, M. Bonchio,
Chem. Eur. J. 2009, 15, 12837–12845.
247; d) M. Brasholz, S. Saubern, G. P. Savage, Aust. J. Chem.
2
011, 64, 1397–1401; e) M. R. Player, D. J. Parks, W. Parsons,
S. K. Meegalla, C. R. Illig, S. K. Ballentine, WO2010 045166;
Chem. Abstr. 2010, 152, 470455; f) G. Griffioen, T. Van Do-
oren, V. Rojas de La Palma, K. Shelley, A. Marchand, S. Alla-
sia, A. Kilonda, P. Chaltin, WO2010 142801; Chem. Abstr.
2011, 154, 64628; g) P. Quadrelli, B. Bovio, A. Piccinini, P.
Caramella, F. De Sarlo, F. Machetti, Tetrahedron 2009, 65,
10679–10684; h) G. Cremonesi, C. La Rosa, P. Dalla Croce, F.
Fontana, C. Fiorelli, Tetrahedron: Asymmetry 2008, 19, 2850–
2855.
6b]
[
[
10] a) R. Taylor, D. R. M. Walton, Nature 1993, 363, 685–693; b)
E. N. Karaulova, E. I. Bagrii, Russ. Chem. Rev. 1999, 68, 889–
9
08; Usp. Khim. 1999, 68, 979–998; c) N. Martín, M. Altable,
S. Filippone, A. Martín-Domenech, Synlett 2007, 3077–3095;
d) P. A. Troshin, R. N. Lyubovskaya, Russ. Chem. Rev. 2008, [28] M. Ohno, A. Yashiro, Y. Tsunenishi, S. Eguchi, Chem. Com-
7, 305–349; Usp. Khim. 2008, 77, 323–369.
mun. 1999, 827–828.
7
[
11] M. A. Yurovskaya, I. V. Trushkov, Russ. Chem. Bull. 2002, 51, [29] E. Trogu, F. De Sarlo, F. Machetti, Chem. Eur. J. 2009, 15,
367–443; Izv. Akad. Nauk Ser. Khim. 2002, 343–413.
7940–7948.
[
12] For 1,3-dipolar cycloadditions, see: M. A. Yurovskaya, A. A.
Ovcharenko, Chem. Heterocycl. Compd. 1998, 34, 261–266;
Teor. Eksp. Khim. Khim. Geterotsikl. Soedin. 1998, 291–297.
13] A. Hirsch, Synthesis 1995, 895–913.
[30] For examples of nitroethane-conjugated addition to electron-
poor olefins, see: a) O. von Schickh, Angew. Chem. 1950, 62,
547–556; b) S. Kambe, H. Yasuda, Bull. Chem. Soc. Jpn. 1966,
39, 2549–2551; c) D. W. Chasar, Synthesis 1982, 10, 841–842;
d) S. G. Zlotin, A. V. Bogolyubov, G. V. Kryshtal, G. M.
Zhdankina, M. I. Struchkova, V. A. Tartakovsky, Synthesis
2006, 22, 3849–3854; e) J. M. Patterson, M. W. Barnes, Bull.
Chem. Soc. Jpn. 1967, 40, 2715–2716.
[
[
14] For first examples, see: a) M. S. Meier, M. Poplawska, J. Org.
Chem. 1993, 58, 4524–4525; b) H. Irngartinger, C. M. Köhler,
U. Huber-Patz, W. Krätschmer, Chem. Ber. 1994, 127, 581–584;
for stable nitrile oxides, see: c) V. N. Drozd, V. I. Sokolov, F. M.
Stoyanovich, Dokl. Akad. Nauk 1994, 339, 52–54; d) M. S. Me-
ier, D. J. Rice, C. Thomas, V. Majidi, R. Pogue, M. Povlawska,
Mater. Res. Soc. Simp. Proc. 1995, 359, 369–372.
[31] A. Corsico Coda, G. Desimoni, A. Gamba, G. Invernizzi, P. P.
Righetti, P. F. Seneci, G. Tacconi, Gazz. Chim. Ital. 1985, 115,
111–118.
[
15] For selected examples, see: a) H. Irngartinger, A. Weber, T.
Escher, Liebigs Ann. 1996, 1845–1850; b) H. Irngartinger, P. W.
Fettel, Tetrahedron 1999, 55, 10753–10760; c) B. Illescas, J.
Rifé, R. M. Ortuño, N. Martín, J. Org. Chem. 2000, 65, 6246–
[32] L. Cecchi, F. De Sarlo, F. Machetti, Eur. J. Org. Chem. 2006,
4852–4860.
[33] a) O. G. Sinyashin, I. P. Romanova, F. R. Sagitova, V. A. Pav-
lov, V. I. Kovalenko, Y. V. Badeev, N. M. Azancheev, A. V. Ilya-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

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/KAP1
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Pages: 11
G. Biagiotti, S. Cicchi, F. De Sarlo, F. Machetti
FULL PAPER
sov, A. V. Chernova, I. I. Vandyukova, Mendeleev Commun.
998, 8, 79–81; b) L. V. Ermolaeva, V. E. Kataev, S. I. Stroby-
[41] R. G. Harvey, T. C. Myers, H. I. Jacobson, E. V. Jensen, J. Am.
Chem. Soc. 1957, 79, 2608–2612.
[42] a) A. Michaelis, R. Kaehne, Ber. Dtsch. Chem. Ges. 1898, 31,
1048–1055; b) A. E. Arbuzov, Ph. D. Dissertation, St. Peters-
burg, 1905; c) A. E. Arbuzov, J. Russ. Phys. Chem. Soc. 1906,
38, 687 (Chem. Zentrabl. 1906, 2, 1639).
[43] B. A. Arbuzov, Pure Appl. Chem. 1964, 9, 307–336.
[44] S. S. Novikov, L. I. Khmel’nitskii, T. S. Novikova, Russ. Chem.
Bull. Int. Ed. 1965, 14, 90–95; Izv. Akad. Nauk SSSR, Ser.
Khim. 1965, 103–110.
[45] R. Ballini, G. Bosica, Eur. J. Org. Chem. 1998, 355–357.
[46] S. G. Zlotin, A. V. Bogolyubov, G. V. Kryshtal, G. M. Zhdank-
ina, M. I. Struchkova, V. A. Tartakovsky, Synthesis 2006, 22,
3849–3854.
1
kin, A. P. Timosheva, V. I. Kovalenko, I. P. Romanova, O. G.
Sinyashin, Izv. Akad. Nauk Ser. Khim. 2002, 51, 593–601.
34] a) K. A. Petrov, V. A. Chauzov, N. N. Bogdanov, I. V. Pastu-
khov, J. Gen. Chem. USSR 1974, 1617; Zh. Obshch. Khim.
[
1974, 44, 1649; b) A. A. Neimysheva, S. S. Muratov, E. V. Smir-
nov, L. M. Solntseva, J. Gen. Chem. USSR 1976, 942; Zh.
Obshch. Khim. 1976, 46, 940.
[
[
35] A. V. Chemagin, N. V. Yashin, Y. K. Grishin, T. S. Kuznetsova,
N. S. Zefirov, Synthesis 2010, 259–266.
36] For another example of base-catalysed oxidative cycloadditons
to [60]fullerene, see: M. Ohno, A. Yashiro, S. Eguchi, Chem.
Commun. 1996, 291–292.
[
37] The reaction was successful with other non-activated nitro
compounds such as benzylnitromethane and 4-nitrobutanoates
but failed with nitromethane.
[47] For an interesting and detailed description of the NMR spectra
of 1f, see: L. T. Byrne, V. Ferro, S. Stevenson, R. V. Stick,
Magn. Reson. Chem. 1994, 32, 749–752.
[48] No furazan side-product was observed, see: L. Cecchi, F.
De Sarlo, C. Faggi, F. Machetti, Eur. J. Org. Chem. 2006, 3016–
3020.
[38] The excess of the activated nitro compound with a pK
a
similar
to that of AcOH provides acidity when the base is catalytic.
39] E. L. Carpenter, H. S. Davis, J. Appl. Chem. 1957, 7, 671–676.
40] A. P. Krapcho, C. S. Kuell, Synth. Commun. 1990, 20, 2559–
[
[
Received: July 25, 2014
2564.
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42990
/KAP1
Date: 28-10-14 18:16:01
Pages: 11
Reactivity of [60]Fullerene with Primary Nitro Compounds
Fullerene Functionalisation
G. Biagiotti, S. Cicchi, F. De Sarlo,
F. Machetti* ................................... 1–11
Reactivity of [60]Fullerene with Primary
Nitro Compounds: Addition or Catalysed
Condensation to Isoxazolo[60]fullerenes
Isoxazolino[60]fullerenes have been syn-
thesised directly from activated nitro com-
pounds by a catalytic process (DABCO or
NMP/[Cu]). The protocol is simple, versa-
tile and tolerant towards diverse functional
groups. A mechanism is proposed to ex-
plain both this condensation and the
known addition with nitroethane in excess
base.
Keywords: Cycloaddition / Condensation
reactions / Fullerenes / Copper / Nitro
compounds
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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