Methodology for the Preparation of C1-Monoalkylated 1,2-Dihydro[C 70] Derivatives: Formation of the Other Regioisomer

Article abstract of DOI:10.1021/jo030242s

Deprotonation of 1,2-C₇₀H₂ with TBAOH, followed by alkylation with methyl bromoacetate, results in formation of a C1-monoalkylated 1,2-dihydro-C₇₀ derivative. The position of the alkyl group (C1) was established by NMR spectroscopy and comparison with literature spectra of C2-monoalkylated analogs. Presumably, C1-alkylation is the major process due to selective deprotonation of 1,2-C₇₀H₂ at C1. Substitution of benzyl bromide for methyl bromoacetate results in rapid dialkylation, unless the amount of base is carefully controlled, in which case C1-monobenzylation is the major process. This methodology for alkylation at C1 is complimentary to methods for the C2-monoalkylation of C₇₀ with Zn and methyl bromoacetate.

Full text of DOI:10.1021/jo030242s

SCHEME 1
Meth od ology for th e P r ep a r a tion of
C1-Mon oa lk yla ted 1,2-Dih yd r o[C70]
Der iva tives: F or m a tion of th e “Oth er ”
Regioisom er
Zhongwen Wang and Mark S. Meier*
Department of Chemistry, University of Kentucky,
Lexington, Kentucky 40506-0055
SCHEME 2
meier@uky.edu
Received J uly 28, 2003
Abstr a ct: Deprotonation of 1,2-C70H2 with TBAOH, fol-
lowed by alkylation with methyl bromoacetate, results in
formation of a C1-monoalkylated 1,2-dihydro-C70 derivative.
The position of the alkyl group (C1) was established by NMR
spectroscopy and comparison with literature spectra of C2-
monoalkylated analogs. Presumably, C1-alkylation is the
major process due to selective deprotonation of 1,2-C70H2 at
C1. Substitution of benzyl bromide for methyl bromoacetate
results in rapid dialkylation, unless the amount of base is
carefully controlled, in which case C1-monobenzylation is
the major process. This methodology for alkylation at C1 is
complimentary to methods for the C2-monoalkylation of C70
with Zn and methyl bromoacetate.
lation at C2.4b Alkylation with methyl bromoacetate
occurs preferentially at C2 (1), although a small amountof
the C5-alkylated (6-H) isomer 2 was isolated (Scheme 1).5
Although the C1-C2 bond is usually the most reactive
bond in C70, it is not clear why C2 alkylation is preferred
over C1 alkylation. Blank experiments with preformed
Reformatsky reagents suggested that the result above
is not due to addition of a zinc enolate. If two-electron
transfer from Zn to C70 occurs and is followed by alky-
lation and protonation steps, the same outcome should
be observed regardless of the method used to generate
the anion. However, we knew that PhCH2Br alkylation
Although fullerene anions (“fullerides”)1 are used in a
number of methods for the formation of dialkylated
fullerenes,2 there are many fewer that produce monoalky-
lated fullerene derivatives from C60 anions. It is possible
to prepare monoalkylated fullerenes by alkylation of
C60n- anions prepared by electrochemical reduction,2d by
photoinduced charge transfer,3 by chemical reduction,4
and by deprotonation of hydrogenated fullerenes.2g
There are even fewer reports of monoalkylation of C70
anions. Reactions of this lower-symmetry fullerene can
produce (at least in principle) many more isomers than
are produced in similar reactions on the icosahedral C60.
We have recently demonstrated that treatment of C70
with Zn and reactive alkyl halides results in monoalky-
2-
of C70 formed by deprotonation of C70H2 resulted in a
set of isomeric dialkylated species, with the major product
resulting from dialkylation near the equator.2g
In an effort to determine if the specific alkyl halide
determined the regiochemistry of alkylation, we gener-
2-
ated C70 by deprotonation of 1,2-C70H2 (3) and then
added methyl bromoacetate. Under these conditions we
obtain the C1-monoalkylated product 4 (29% absolute
yield, 37% based on consumed C70), with only trace
quantities (∼1% yield) of the C2-monoalkylated isomer
1 (Scheme 2). This regiochemistry is the opposite of that
obtained in the Zn/RX reaction (Scheme 1) and quite
unlike the course that the reaction takes when C70H2 is
treated with excess base and excess PhCH2Br.
(1) Reed, C. A.; Bolskar, R. D. Chem. Rev. 2000, 100, 1075-1119.
(2) For examples, see: (a) Caron, C.; Subramanian, R.; D’Souza, F.;
Kim, J .; Kutner, W.; J ones, M. T.; Kadish, K. M. J . Am. Chem. Soc.
1993, 115, 8505-8506. (b) Chen, J .; Cai, R.-F.; Huang, Z.-E.; Wu, H.-
M.; J iang, S.-K.; Shao, Q.-F. J . Chem. Soc., Chem. Commun. 1995,
1553-1554. (c) Fukuzumi, S.; Suenobu, T.; Hirasaka, T.; Arakawa, R.;
Kadish, K. M. J . Am. Chem. Soc. 1998, 120, 9220-9227. (d) Kadish,
K. M.; Gao, X.; Caemelbecke, E. V.; Hirasaka, T.; Suenobbu, T.;
Fukuzumi, S. J . Phys. Chem. A 1998, 102, 3898-3906. (e) Fukuzumi,
S.; Suenobu, T.; Hirasaka, T.; Arakawa, R.; Kadish, K. M. J . Am. Chem.
Soc. 1998, 120, 9220-9227. (f) Allard, E.; Delaunay, J .; Cheng, F.;
Cousseau, J .; Ordu´nam, J .; Gar´ın, J . Org. Lett. 2001, 3, 3503-3506.
(g) Meier, M. S.; Bergosh, R. G.; Gallagher, M. E.; Spielmann, H. P.;
Wang, Z. J . Org. Chem. 2002, 67, 5946-5952.
The regiochemistry of alkylation in 1, 2, and 4 was
established by comparison of the absorption spectra with
those of previously reported 1,2-adducts (Figure 1).
The specific orientation of alkylation at the C1-C2
1
bond in 1 and 4 was established by comparison of H
chemical shifts of the CH2 groups. It is known that groups
held over the pole of C70 exhibit resonances that are
shifted downfield relative to the resonances of groups
(3) Fukuzumi, S.; Hirasaka, T.; Suenobu, T.; Ito, O.; Fujitsuka, M.;
Arakawa, R. Proc. Electrochem. Soc. 1998, 98, 296-309; Mikami, K.;
Matsumoto, S.; Ishida, A.; Takamuku, S.; Suenobu, T.; Fukuzumi, S.
J . Am. Chem. Soc. 1995, 117, 11134-11141.
(4) (a) Chen, J .; Cai, R.-F.; Huang, Z.-E.; Wu, H.-M.; J iang, S.-K.;
Shao, Q.-F. J . Chem. Soc., Chem. Commun. 1995, 1553-1554. (b)
Wang, Z.; Meier, M. S. J . Org. Chem. 2003, 68, 3042-3048. (c) Allard,
E.; Delaunay, J .; Cousseau, J . Org. Lett. 2003, 5, 2239-2242.
(5) The numbering system used here is the “trivial” system described
in Powell, W. H.; Cozzi, F.; Moss, G. P.; Thilgen, C.; Hwu, R. J .-R.;
Yerin, A. Pure Appl. Chem. 2002, 74, 629-695.
10.1021/jo030242s CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/20/2004
2178
J . Org. Chem. 2004, 69, 2178-2180

support for this notion is provided by calculations that
have predicted that the C1 proton of 3 should be
significantly more acidic than the C2 proton.9 As the
amount of base is increased, an increasing amount of
2-
C70
is produced, dialkylation becomes increasingly
important, and the product distribution resembles the
dialkylation we observed previously. In the range of
stoichiometry we investigated here we are able to observe
both dialkylated and monoalkylated species. Interest-
ingly, no C7-monoalkylated material was isolated, sug-
gesting that 7-benzylC70- anion is more nucleophilic than
-
-
either of the 1-benzylC70 or 2-benzylC70 anions.
This work provides a useful route to C1-monoalkylated
C70 derivatives. In tandem with the Zn/RX method,4b it
is possible to prepare either one of the two C1-C2
regioisomers. The results herein suggest that the Zn/RX
method2f does not involve alkylation of the same discrete
anions that are formed by deprotonation of hydrogenated
fullerenes.
F IGURE 1. Absorption spectra of 1, 3, and 4.
Exp er im en ta l Section
Meth yl ([70]F u ller en -1(2H)-yl) Aceta te (4). 1,2-C70H2 (3)10
(86.0 mg, 0.102 mmol), methyl bromoacetate (1.52 g, 10.0 mmol),
and benzonitrile (50 mL) were combined in a 100-mL Schlenk
flask. TBAOH (2.0 mL, 1.0 M in methanol, 2.0 mmol) was placed
in another 25-mL Schlenk flask, and most of the methanol was
removed by evaporation. The two flasks were connected with a
distillation head and deoxygenated for 10 FPT cycles. After
warming to room temperature the contents of these two flasks
were mixed thoroughly, and the mixture was stirred under Ar
at room temperature for 5 days. Unreacted anions and base were
quenched with 2 mL of acetic acid. Ammonium salts were
removed by passing the solution through a silica plug and eluting
with toluene. The solvents were evaporated under vacuum, and
the resulting solid was dissolved in ∼15 mL of toluene and
applied to a silica gel chromatography column. The column was
eluted with toluene to produce a first fraction of recovered C70
(17.6 mg, 0.021 mmol)) and a second fraction containing the
alkylated products. The second fraction was further purified with
preparative HPLC (10 mm × 250 mm Cosmosil Buckyprep
column, toluene as mobile phase, monitored at 310 nm), produc-
ing 4 (27.5 mg, 0.030 mmol, 29% yield (37% based on consumed
C70)) and 14 (1.2 mg, 0.0013 mmol, 1.3%). 1H NMR: δ 3.50 (s,
2H), 3.91 (s, 3H), 5.17 (s, 1H). 13C NMR: δ 46.79 (1C), 50.26
(1C), 52.38 (1C), 54.62 (1C), 131.51 (2C), 131.59 (2C), 131.80 (2C),
134.10 (2C), 134.32 (2C), 138.38 (2C), 140.15 (2C), 141.11 (2C),
143.08 (2C), 143.26 (2C), 143.40 (2C), 143.43 (2C), 145.38 (2C),
146.26 (2C), 146.49 (2C), 146.62 (2C), 147.18 (1C), 147.25 (2C),
147.28 (2C), 147.76 (2C), 149.06 (2C), 149.28 (2C), 149.73 (2C),
149.76 (2C), 150.16 (2C), 150.22 (2C), 150.29 (2C), 150.81 (2C),
150.88 (2C), 151.63 (2C), 151.70 (3C), 151.81 (2C), 156.73 (2C),
156.99 (2C), 169.95 (1C). MS: 914.0 (60%, calcd 914.0); 840.0
(100%).
F IGURE 2. The products of the reaction of PhCH2Br with
1,2-C70H2 and limited amounts of base.
help over the side,6 and we assign structure 4 on the basis
of an absorption spectrum that is a very close match to
that of 1 and 3, a 13C NMR spectrum consistent with the
1
symmetry, a H NMR shift of the fullerene C-H that is
downfield of the corresponding resonance in 1,2g and a
1H NMR shift of the acetate CH2 that is upfield of the
corresponding resonance in 1 (Scheme 2).
We found that when PhCH2Br is used in place of
BrCH2CO2CH3, the outcome of the reaction is very
dependent on the amount of base added. When 1.2 equiv
of TBAOH and excess PhCH2Br are used, the C1 alky-
lated species 5 was the only product isolated (7% absolute
yield, 22% yield based on unrecovered fullerene).7 When
3.6 equiv of TBAOH was added, presumably furnishing
more of the C702- dianion, both of two possible mono 1,2-
isomers (5, 20% based on unrecovered fullerene, and 6,
2%) were produced, together with a 25% combined yield
of the diadducts reported previously (Figure 2).2g,8 The
structures of 5 and 6 were assigned in the same manner
used above. When stoichiometric amounts of BrCH2Ph
were used with an excess of TBAOH, most of the starting
material (3) was converted to C70 and only traces of
monoalkylated products were observed in HPLC.
Reaction s of 1,2-C70H2 with Ben zyl Br om ide an d TBAOH
in P h CN. Rea ction A (1.2 equ iv of ba se, excess RX). C70H2
(3, 62.0 mg, 0.074 mmol), benzyl bromide (1.27 g, 7.4 mmol),
and benzonitrile (50 mL) were combined in a 100-mL flask,
TBAOH (9.0 mL, 0.01 M in methanol, 0.090 mmol, then vacuum
evaporation of methanol), present in a separate 25-mL Schlenk
flask, was connected through a distilling head and deoxygenated
for 10 FPT cycles. The apparatus was then tipped to mix the
reagents. After being stirred for 18 h, the mixture was worked
up as with 4 (only without the silica gel column separation step).
After being purified by preparative HPLC (10 mm × 250 mm
Cosmosil Buckyprep column, toluene as mobile phase, monitored
Monoalkylation at C1 with benzyl bromide is only
observed when using limited amounts of base. This result
suggests that the first deprotonation of 3 occurs prefer-
entially at C1, leading to alkylation at that carbon. Some
(6) Meier, M. S.; Poplawska, M.; Compton, A. L.; Shaw, J .; Selegue,
J . P.; Guarr, T. F. J . Am. Chem. Soc. 1994, 116, 7044-7048.
(7) Unreacted 3 (10%) and C70 (60%) were also recovered.
(8) Structures 7 and 8 were assigned earlier, and several additional
isomeric dialkylated compounds (9, 10) were isolated, but structures
could not be definitively assigned. See ref 2g.
(9) Van Lier, G.; De Proft, F.; Geerlings, P. Chem. Phys. Lett. 2002,
366, 311-320.
(10) Spielmann, H. P.; Wang, G.-W.; Meier, M. S.; Weedon, B. R. J .
Org. Chem. 1998, 9865, 5-9871.
J . Org. Chem, Vol. 69, No. 6, 2004 2179

at 310 nm), C70 (37.2 mg, 0.044 mmol, 60%) and 5 (4.7 mg, 0.0050
mmol, 6.8%, 22% based on unrecovered fullerene) were obtained,
together with unreacted 3 (6.5 mg, 0.0077 mmol, 10%). Rea ction
B (3.6 equ iv of ba se, excess RX). C70H2 (3, 93.0 mg, 0.110
mmol), benzyl bromide (1.95 g, 11.4 mmol), benzonitrile (60 mL),
and TBAOH (40.1 mL, 0.01 M in methanol, 0.41 mmol, then
vacuum evaporation of methanol) were employed as the similar
procedure and workup as above. After being purified with
preparative HPLC (10 mm × 250 mm Cosmosil Buckyprep
column, toluene as mobile phase, monitored at 310 nm), C70 (37.2
mg, 0.044 mmol, 40%), 5 (12.2 mg, 0.013 mmol, 12% absolute
yield, 20% based on unrecovered fullerene), 6 (1.2 mg, 0.0013
mmol, 1.9%), 7 ((7,23-C70Bn2), 6.1 mg, 0.0060 mmol, 10%), and
two unidentified isomeric species 9 (6.8 mg, 11%) and 10 (2.6
mg, 4.4%) were produced. Rea ction C (28 equ iv of ba se,
excess RX). C70H2 (3, 59.1 mg, 0.0702 mmol), benzyl bromide
(0.85 g, 5.0 mmol), and benzonitrile (60 mL) and TBAOH (2.0
mL, 1.0 M in methanol, 2.0 mmol, then vacuum evaporation of
methanol) were employed as the similar procedure and workup
as above. After being purified with preparative HPLC (10 mm
× 250 mm Cosmosil Buckyprep column, toluene as mobile phase,
monitored at 310 nm), 7 (7.2 mg, 0.0070 mmol, 10%), 9 (7.1 mg,
10%), 10 (0.7 mg, 1%), and 8 (0.8 mg, 1%) were produced, along
with C70 (4.1 mg, 0.0049 mmol, 7%) and unreacted 3 (1.5 mg,
0.0018 mmol, 2.5%).
(2C), 146.20 (2C), 146.54 (2C), 146.94 (2C), 147.13 (1C), 147.22
(2C), 147.30 (2C), 147.74 (2C), 149.04 (2C), 149.21 (2C), 149.64
(2C), 149.80 (2C), 149.98 (2C), 150.14 (2C), 150.24 (2C), 150.80
(2C), 150.87 (2C), 151.45 (2C), 151.67 (3C), 151.83 (2C), 156.74
(2C), 158.42 (2C); MS: 932.1 (30%, calcd 932.0); 840.0 (100%).
2-Ben zyl-1,2-d ih yd r o[70]fu ller en e (6). 1H NMR: δ 4.12 (s,
2H), 4.56 (s, 1H), 7.45 (t, 1H), 7.53 (t, 2H), 7.70 (t, 2H). 13C
NMR: δ 52.13 (1C), 53.00 (1C), 57.95 (1C), 128.17 (1C), 129.23
(2C), 131.40 (2C), 131.51 (2C), 131.72 (2C), 134.20 (2C), 134.26
(1C), 135.73 (2C), 138.34 (2C), 140.65 (2C), 141.13 (2C), 142.88
(2C), 143.20 (2C), 143.27 (2C), 143.49 (2C), 145.77 (2C), 145.95
(2C), 146.23 (2C), 146.70 (2C), 147.05 (2C), 147.47 (2C), 147.64
(2C), 147.86 (2C), 149.19 (2C), 149.29 (2C), 149.51 (2C), 149.55
(1C), 149.79 (2C), 149.88 (2C), 150.03 (2C), 150.22 (2C), 151.02
(2C), 151.08 (2C), 151.49 (2C), 151.62 (3C), 151.67 (2C), 155.67
(2C), 158.78(2C); MS: 932.0 (25%, calcd 932.0); 840.0 (100%).
Ack n ow led gm en t. The authors thank the National
Science Foundation (grant CHE 9816339) for financial
support of this project. The NMR instruments used in
this work were obtained with support from NSF CRIF
grant CHE-9974810.
1-Ben zyl-1,2-d ih yd r o[70]fu ller en e (5). 1H NMR: δ 3.82 (s,
2H), 5.06 (s, 1H), 7.34-7.43 (m, 3H), 7.48-7.52 (m, 2H). 13C
NMR: δ 49.69 (1C), 50.57 (1C), 59.29 (1C), 128.11 (1C), 129.03
(2C), 131.41 (2C), 131.27 (2C), 131.64 (1C), 134.07 (2C), 134.13
(2C), 135.37 (2C), 137.71 (2C), 140.37 (2C), 141.18 (2C), 143.00
(2C), 143.18 (2C), 143.32 (2C), 143.37 (2C), 143.44 (2C), 145.39
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal information and copies of the 13C NMR spectra of 4-6. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O030242S
2180 J . Org. Chem., Vol. 69, No. 6, 2004