Catalytic radical acetylation of adamantanes with biacetyl by a cobalt salt under atmospheric dioxygen

Article abstract of DOI:10.1039/a902384d

Exposure of a mixture of adamantane and biacetyl under O₂ in the presence of Co(OAc)₂ (0.1 mol%) in AcOH led to 1-acetyladamantane (47%) and 1,3-diacetyladamantane (20%) as major products along with small amounts of adamantan-1-ol (4%) and adamantan-2-one (3%).

Full text of DOI:10.1039/a902384d

Catalytic radical acetylation of adamantanes with biacetyl by a cobalt salt
under atmospheric dioxygen
Arata Kishi, Susumu Kato, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering and High Technology, Research Center, Kansai
University, Suita, Osaka 564-8680, Japan. E-mail: ishii@ipcku.kansai-u.ac.jp
Received (in Cambridge, UK) 24th March 1999, Accepted 11th June 1999
Exposure of a mixture of adamantane and biacetyl under O2
in the presence of Co(OAc)2 (0.1 mol%) in AcOH led to
1-acetyladamantane (47%) and 1,3-diacetyladamantane
(20%) as major products along with small amounts of
adamantan-1-ol (4%) and adamantan-2-one (3%).
mantan-1-ol 4 (6%) along with several oxygenated products
such as adamantan-1-ol 5 (4%) and adamantan-2-one 6 (3%)
(run 1). Photoacetylation of 1 with biacetyl is reported to form
2 in 13.8% under N2 and 40% under O2, but no diacetyl
compound 3 is formed.1 Therefore, our reaction provides an
efficient catalytic method for the synthesis of acetyl derivatives
of 1 which are technically interest compounds. When the
acetylation was carried out for 4 h, 3 was obtained in preference
to 2 (run 2). Among the solvents examined, AcOH was found to
be the best solvent (runs 3 to 5). From the mechanistic point of
view, it is important to note that no reaction takes place when a
CoIII ion was employed in place of the CoII ion (run 6). The
reaction proceeded smoothly even in the presence of a very
small amount (0.01 mol%) of Co(OAc)2 or Co(acac)2 at 80 °C
to give 2 and 3 in satisfactory yields (runs 7 to 9). When the
amount of biacetyl was reduced to half (3 equiv.) so that the
concentration of biacetyl was halved with respect to O2, the
selectivity to 2 decreased and the amount of partly oxygenated
4 increased (run 10). In the absence of biacetyl, however, no
reaction took place and the starting 1 was recovered unchanged
(run 11). This fact shows that the aerobic oxidation of 1 is also
induced by the presence of biacetyl. The reaction did not take
place either in the presence of hydroquinone (0.1 mol%) or in
the absence of O2 (runs 12 and 13). These observations strongly
suggest that a radical chain process is involved in the present
acetylation, and that molecular oxygen is an essential compo-
nent to promote the acetylation. Indeed, adamantyl radical,
generated in situ from 1-bromoadamantane (3 mmol) by the
action of Bu3SnH (3.6 mmol) and AIBN (0.3 mmol) in AcOH
(3 ml) reacted with biacetyl (18 mmol) and O2 (1 atm) at 80 °C
for 4 h to form 2 and 5 in 5 and 4% yields, respectively, although
it abstracted more easily the hydrogen atom from the Bu3SnH to
give 1 (39%) as the major product. The reaction using benzil in
place of biacetyl resulted in the recovery of the starting
materials (run 14).‡
The introduction of an acyl group to alkanes is one of the most
difficult transformations in organic synthesis. Until recently,
there have been a few reports on the acetylation of cycloalkanes
under irradiation of light or by using a radical initiator such as
benzoyl peroxide.1–4 Although the catalytic acetylation of
alkanes is of interest and would be more useful in organic
synthesis, such a method has not yet been developed. Here, we
report the first successful catalytic radical acetylation of
adamantanes using biacetyl as an acetylating agent by a cobalt
salt under O2 atmosphere [eqn. (1)].
O
Co(OAc)2 (cat.)
+
O2 (1 atm), AcOH, 60 °C
O
1
O
O
O
+
+
(1)
OH
O
2
3
4
Table 1 shows the results for the acetylation of adamantane 1
with biacetyl under various conditions.† The acetylation of 1
with biacetyl in the presence of Co(OAc)2 (0.1 mol%) and O2 (1
atm) in AcOH at 60 °C for 2 h gave 1-acetyladamantane 2
(47%), 1,3-diacetyladamantane 3 (20%) and 3-acetylada-
Table 1 Acetylation of 1 with biacetyl catalyzed by metal saltsa
Yield (%)
Run Metal salt (mol%)
Solvent
t/h
Conversion (%)
2
3
4
5
6
1
2b
3
4
5
Co(OAc)2 (0.1)
Co(OAc)2 (0.1)
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
Co(acac)3 (0.1)
Co(OAc)2 (0.01)
Co(acac)2 (0.01)
AcOH
AcOH
AcOH
ClCH2CH2Cl
MeCN
AcOH
AcOH
AcOH
2
4
2
2
2
2
4
4
4
4
2
2
2
4
94
99
> 99
65
47
22
10
51
20
37
30
4
6
10
11
trace
—
4
2
1
2
1
3
4
4
3
2
trace
—
trace
6
no reaction
98
92
77
98
no reaction
no reaction
no reaction
no reaction
7c
21
49
51
20
35
28
14
25
9
4
1
2
2
2
4
5
5
3
4
8c
9c
Co(OAc)2 (0.0025) AcOH
10d
11e
12f
13g
14h
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
Co(OAc)2 (0.5)
AcOH
AcOH
AcOH
AcOH
AcOH
16
a
b
f
1 (3 mmol) was allowed to react with biacetyl (6 equiv., 18 mmol) in the presence of a metal salt under O2 (1 atm) in AcOH (3 ml) at 60 °C.
Polyfunctionalyzed products and adamantane-1,3-diol were also formed. 80 °C Biacetyl (3 equiv., 9 mmol) was used. In the absence of biacetyl.
Hydroquinone (0.1 mol%) was added. g Under argon. h Benzil was used in place of biacetyl.
c
d
e
Chem. Commun., 1999, 1421–1422
1421

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In order to gain insight into the role of cobalt salts in the
present reaction, acetylations of 1 with biacetyl by CoII and
CoIII ions under O2 (1 atm) at 75 and 80 °C were monitored by
GC at appropriate time intervals (Fig. 1). The acetylation of 1
was efficiently catalyzed by CoII at 75 °C, while the reaction
with CoIII did not take place at all at this temperature. However,
when the reaction temperature was raised to 80 °C, the
acetylation of 1 by CoIII was prompted after an induction period
of about 1 h. It is well-known that CoIII ions are reduced to CoII
ions by organic substrates such as toluene and cyclohexane via
a one-electron transfer process.§ Therefore, the induction
period of about 1 h observed at 80 °C would correspond to the
time needed for the formation of CoII by the one-electron
transfer to CoIII from biacetyl and/or 1. At 75 °C, however,
owing to the difficulty of the electron transfer to CoIII from
these substrates, no acetylation is induced. Therefore, if the
reduction of CoIII to CoII is performed by adding an additive like
aldehyde, 1 was acetylated by CoIII even at 75 °C [eqn. (2)].
These findings indicate that the CoII ion, which reacts easily
with O2 to generate labile dioxygen complexes such as a
superoxocobalt(iii) or m-peroxocobalt(iii) complex, plays an
important role in the present acetylation [eqns. (3) and (4)].7,8
Fig. 1 Time-dependence curves for the conversion of 1 with biacetyl
catalyzed by Co(acac)2, Co(acac)3 and Co(acac)3 combined with benzalde-
hyde in AcOH at 75 or 80 °C. Conditions: 1 (3 mmol), biacetyl (18 mmol),
AcOH (3 ml), cobalt salt (3.0 3 1024 mmol), benzaldehyde (1.5 3 1022
mmol).
tion by Co ions to generate a radical species which acts as a
radical carrier. In fact, the reaction of 1 (3 mmol) with biacetyl
(18 mmol) under the influence of MCPBA (3.6 mmol) and CoIII
(0.015 mmol) in acetic acid (3 ml) in an inert atmosphere at
60 °C for 1 h afforded 2 with 60% selectivity, although the
conversion of 1 was low (5%) probably because of the rapid
decomposition of MCPBA by Co ion.
In order to extend the present acetylation to substituted
adamantanes, 1,3-dimethyladamantane 8 and 5 were allowed to
react with biacetyl under the same reaction conditions as
employed for 1 in Table 1, run 3. As expected, 8 was
satisfactorily acetylated to the corresponding mono- and di-
acetyladamantanes in 54 and 21% yields, respectively. Sim-
ilarly, 5 afforded 4 in 54% yield along with 3,5-diacetylada-
mantan-1-ol (7%). It is interesting to note that the reaction of 5
with biacetyl did not take place on the hydroxy function, which
is different from the usual acetylation procedure using Ac2O or
AcCl, in which the hydroxy group is preferentially acetylated.
This work was partly supported by a Grant-in-Aid for
Scientific Research (No.10450337) from Monbusho.
CoIII
PhCO•
(2)
(3)
CoII
H+
+
+
+
PhCHO
LnCoII
LnCoIII-O-O•
+
O2
superoxocobalt(III)
+ LnCoIII
LnCoIII-O-O•
(4)
LnCoIII-O-O-CoIIILn
µ-peroxocobalt(III)
Although the mechanistic details are still obscure, the fact
that the acetylation did not take place with CoII in the absence
of O2 or with CoIII even in the presence of O2 suggests that a
cobalt(iii)–oxygen complex is the key species in the present
acetylation of 1 with biacetyl. The resulting cobalt(iii)-oxygen
complex reacts with biacetyl to generate an acetyl radical which
is readily trapped by O2 under the present conditions to form an
acetyl peroxyl radical [eqns. (5) and (6)]. The formed acetyl
peroxyl radical undergoes hydrogen abstraction from 1 to form
an adamantyl radical 7 and peracetic acid [eqn. (7)]. The formed
radical 7 would react with biacetyl to give 2 and an acetyl
radical which serves as a chain carrier in the reaction [eqn. (8)].
In addition, 7 reacts with O2 to produce oxygenated products 5
and 6 [eqn. (9)]. Under the present reaction conditions in which
O2 exists in the reaction system, the direct abstraction of the
hydrogen from 1 by the acetyl radical may be disregarded, since
the rate of hydrogen abstraction from an alkane by acetyl radical
is much slower than that of the addition of O2 to acetyl radical.¶
The acetyl peroxyl radical can also abstract the hydrogen from
1 to form 7 and peracetic acid. It is probable that peracetic acid
formed in the reaction is easily subjected to redox decomposi-
Notes and references
† Typical reaction: To a solution of adamantane 1 (3 mmol) and Co(OAc)2
(0.1 mol%) in AcOH (3 ml) was added biacetyl (18 mmol), and the mixture
was stirred under O2 (1 atm) at 60 °C for 2 h. Products were isolated by
column chromatography on silica gel with hexane–EtOAc.
‡ Treatment of biacetyl with O2 in the presence of CoII under these
conditions afforded AcOH in 192% (based on CoII), however, benzil was
recovered unchanged by the same treatment.
§ The reaction of a CoIII ion with cyclohexane (ref. 5) or alkylbenzenes (ref.
6) is known to involve one-electron transfer from the substrate to CoIII
,
yielding a CoII ion and radical cation which readily liberates H+ to give an
alkyl radical.
O
Co
III–oxygen
complex (cat.)
O
(5)
¶ The reaction of acetyl radical with O2 is reported to occur very fast [k =
(1.8 ± 0.5) 3 109 M21 s21] compared with the hydrogen abstraction from
n-hexane by acetyl radical (k @ 5 3 103 M21 s21) (ref. 9).
•
O
O
O
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91, 6830.
(6)
(7)
+
O2
•
OO•
O
•
O
+
+
1
6 A. Onopchenko and J. G. D. Shultz, J. Org. Chem., 1973, 38, 3729.
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Chem. Soc., 1980, 102, 5511.
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2398.
OO•
OOH
7
O
O
+
+
+
(8)
7
7
2
5
•
9 E. B. Carl, G. N. Anthony, M. R. David, U. I. Keith and L. Janusz, Aust.
J. Chem., 1995, 48, 363.
O
O2
+
(9)
6
Communication 9/02384D
1422
Chem. Commun., 1999, 1421–1422