Efficient oxidation of adamantanes by sodium nitrite with molecular oxygen in trifluoroacetic acid

Article abstract of DOI:10.1055/s-2006-950422

Oxidation of adamantanes by oxygen was effectively achieved by use of sodium nitrite as a catalyst in trifluoroacetic acid (TFA) to give 1-adamantyl trifluoroacetates, from which adamantanols were obtained in good yields. A catalytic amount of sodium nitrite was essential and TFA was the best solvent among solvents examined for this oxidation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950422

LETTER
2415
Efficient Oxidation of Adamantanes by Sodium Nitrite with Molecular
Oxygen in Trifluoroacetic Acid
O
xidation of Adam
s
antanes
b
a
yNaNO
w
2 mith Molecular
O
xyg
u
en in TFA Onomura,a Yutaka Yamamoto,a Noriaki Moriyama,a Fumiaki Iwasaki,b Yoshihiro Matsumura*a
a
Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyomachi, Nagasaki 852-8521, Japan
Fax +81(95)8192476; E-mail: matumura@net.nagasaki-u.ac.jp
b
Tsukuba Research Lab, Tokuyama Co. Ltd., 40 Wadai, Tsukuba 300-4247, Japan
Received 1 June 2006
A typical condition of our method is as follows: a solution
of 1a in TFA containing 0.2 equivalent of NaNO2 was
stirred at room temperature under an oxygen atmosphere.
Since the organic extract of the reaction was a mixture of
Abstract: Oxidation of adamantanes by oxygen was effectively
achieved by use of sodium nitrite as a catalyst in trifluoroacetic acid
(TFA) to give 1-adamantyl trifluoroacetates, from which adaman-
tanols were obtained in good yields. A catalytic amount of sodium
nitrite was essential and TFA was the best solvent among solvents 1-adamantyl trifluoroacetate (2a) and a small amount of
examined for this oxidation.
3a, it was then treated with an aqueous 1 N HCl solution
overnight followed by extraction with dichloromethane to
afford 3a in 96% yield without contamination of 2a.
Similar reaction of methyl-substituted adamantanes 1b,c
with oxygen afforded methyl-substituted adamantanols
3b,c in good yields. These results were shown in Table 1
(entries 3-5).
Key words: alcohols, hydrocarbons, oxidations, oxygen, radical
reactions
Oxidation of adamantane (1a) to 1-adamantanol (3a) has
continued to attract much interest because of a versatility
of 3a in material sciences.1 Among a variety of methods
for the transformation of 1a to 3a or its derivatives,2 use
of oxygen as an oxidant is worthwhile from both econom-
ical and mechanistic viewpoints; iron(III)–aldehyde–O2,3
iron(II)–hydrogen sulfide–O2,4 N-hydroxyphthalimide–
O2,5 titanium oxide–hn–O2,6 electrochemical reduction–
Tl(III) porphyrin–O2,7 Ru(III) polyoxometalate–O2,8 and
V(IV) polyoxometalate–O2.9 However, these reported
methods give 3a in low yields and require some metal ion
or organic halide catalyst under drastic conditions. We
report herein an efficient method for oxidation of adaman-
tanes 1a–c to 1-adamantanols 3a–c using a catalytic
amount of easily available sodium nitrite (NaNO2) with
molecular oxygen (Scheme 1).
In order to give some insight into the reaction mechanism,
oxidation of 1a-c was carried out under a variety of reac-
tion conditions (entries 1, 2 and 6-17 in Table 1).
The results indicated that three kinds of factors were
critical for the oxidation of 1a-c to 3a-c. First one is the
effect of NaNO2 as a catalyst on the yield of 3a. That is,
the absence of NaNO2 did not cause any oxidation of 1a
(entry 1) but only one mol% of NaNO2 was enough for the
completion of the oxidation of 1a (entry 2). Nitrosonium
tetrafluoroborate10 was usable in place of NaNO2 (entry
6), whereas NaNO3 did not cause any oxidation of 1a
(entry 7).
The second one was the oxygen effect. The reactions in
entries 1–7 were carried out under an oxygen atmosphere
(1 atm) or an aerobic condition where satisfactory results
were obtained when NaNO2 was used as a catalyst (entries
2-5 and 8). However, the yield of 3a was a lowly 10%
under a nitrogen atmosphere even if 0.2 equivalent of
NaNO2 was used (entry 9). Another noticeable point was
that the yields of 3a were dependent on the amount of
NaNO2 (46% for 1 equiv of NaNO2, entry 10; and 92% for
2 equiv of NaNO2, entry 11).
R1
R1
O2
cat. NaNO2
OCOCF3
in CF3CO2H
r.t. 3 h
R2
R2
1a–c
2a–c
R1
The third one was the solvent effect. Acetic acid and
methanesulfonic acid were not suitable for the oxidation
(entries 12 and 13) but a prolonged reaction time gave 3a
in a satisfactory yield in the latter solvent (entry 14). Chlo-
rodifluoroacetic acid was a usable solvent for this oxida-
tion (entry 16), while difluoroacetic acid was not (entry
15). The use of concentrated sulfuric acid resulted in the
formation of a mixture of 3a and 2-adamantanone in low
yields (entry 17).1a
10% HCl
a; R1 = R2 = H
b; R1 = H, R2 = Me
c; R1 = R2 = Me
OH
R2
3a–c
Scheme 1
SYNLETT 2006, No. 15, pp 2415–2418
1
8
.0
9
.2
0
0
6
Advanced online publication: 08.09.2006
DOI: 10.1055/s-2006-950422; Art ID: U06206ST
© Georg Thieme Verlag Stuttgart · New York

2416
O. Onomura et al.
LETTER
Table 1 Oxidation of Adamantane 1a-ca
Entry
1
Substrate
1a
Catalyst
–
(equiv)
(–)
Solvent
TFA
Atmosphere
Time (h)
Product 3a-c Yield (%)b
O2
O2
O2
O2
O2
O2
O2
Air
N2
N2
N2
O2
O2
O2
O2
O2
O2
24
3
3a
3a
3a
3b
3c
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
0
92
96
96
96
91
0
2
1a
NaNO2
NaNO2
NaNO2
NaNO2
NOBF4
NaNO3
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
NaNO2
(0.01)
(0.2)
(0.2)
(0.2)
(0.2)
(1.0)
(0.2)
(0.2)
(1.0)
(2.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
TFA
3
1a
TFA
3
4
1b
1c
TFA
3
5
TFA
3
6
1a
TFA
3
7
1a
TFA
3
8
1a
TFA
3
92
10
46
92
0
9
1a
TFA
3
10
11
12
13
14
15
16
17
1a
TFA
3
1a
TFA
3
1a
AcOH
MsOH
MsOH
HCF2CO2H
ClCF2CO2H
concd H2SO4
24
3
1a
7
1a
72
24
3
89
15
93
31c
1a
1a
1a
24
a The reaction was carried out by stirring a solution of substrate (1 mmol) and a catalyst in a solvent (5 mL) at r.t. under an atmosphere described
in the table.
b Isolated yield after an overnight treatment of the reaction mixture with 1 N HCl (10 mL).
c In addition, 2-adamantanone (18%) was isolated as a byproduct.
Further information about the mechanism was speculated of products 3a-c, which were not dependent on the num-
on the basis of the ratios of the oxidation products in com- ber of bridgehead hydrogens of 1a-c (entries 4-6).
petitive oxidation reactions between 1a, 1b, and 1c by
An involvement of radical species in those oxidation reac-
NaNO2 and by electrochemical method,2m which has been
tions was then examined by adding TEMPO (2,2,6,6-tet-
known to initiate the oxidation of 1a with electron-trans-
fer (Scheme 2). The results are summarized in Table 2, in
which the ratios of products 3a-c almost depended on the
ramethyl-1-piperidinyloxy) as a radical scavenger11 to a
solution for oxidation of 1a. In the oxidation of 1a by O2–
NaNO2, as the amount of TEMPO increased, the yield of
number of bridgehead hydrogens of 1a-c in the competi-
product 3a decreased (Scheme 3), while in the electro-
tive oxidation reactions by NaNO2 (entries 1-3). Whereas
chemical oxidation of 1a addition of 0.2-1.0 equivalent
of TEMPO did not show any effect on the reaction
(Scheme 4).
the competitive oxidation reactions between 1a-c by
electrochemical method afforded 3a-c with 1.1-1.3 ratio
Electrochemical Oxidation
NaNO2 Oxidation
– [e] (1F/mol)
1)
1)
N2
Et4NBF4
NaNO2 (0.5 mmol)
or
in CF3CO2H–CH2Cl2
r.t. 3 h
in CF3CO2H–CH2Cl2
r.t.
+
1a,b
1b,c
3a,b
+
3b,c
0.5 mmol
2) aq NaOH, cetyltrimethylammonium hydroxide
overnight
0.5 mmol
Scheme 2 Competitive oxidation reaction between 1a-c by NaNO2 and by electrochemical method
Synlett 2006, No. 15, 2415–2418 © Thieme Stuttgart · New York

LETTER
Oxidation of Adamantanes by NaNO2 with Molecular Oxygen in TFA
2417
Table 2 Competitive Reactions between 1a–c by NaNO2a and Electrochemical Oxidationb
Entry
Substrate 1a,b (R1, R2)/1b,c (R1, R2)
Number of bridge- Oxidation method
head hydrogen (ratio)
Productc Ratio of product
3a,b/3b,c
1
2
3
4
5
6
1a (R1 = R2 = H)/1b (R1 = H, R2 = Me)
1a (R1 = R2 = H)/1c (R1 = R2 = Me)
1b (R1 = H, R2 = Me)/1c (R1 = R2 = Me)
1a (R1 = R2 = H)/1b (R1 = H, R2 = Me)
1a (R1 = R2 = H)/1c (R1 = R2 = Me)
1b (R1 = H, R2 = Me)/1c (R1 = R2 = Me)
4/3 (1.3)
4/2 (2.0)
3/2 (1.5)
4/3 (1.3)
4/2 (2.0)
3/2 (1.5)
NaNO2
3a/3b
3a/3c
3b/3c
3a/3b
3a/3c
3b/3c
1.4
2.2
1.5
1.1
1.3
1.1
NaNO2
NaNO2
Electrochemical oxidation
Electrochemical oxidation
Electrochemical oxidation
a The reaction was carried out by stirring a solution of substrates (each 0.5 mmol) and NaNO2 (0.5 mmol) in a mixture of TFA (5 mL) and
CH2Cl2 (3 mL) at r.t. under a nitrogen atmosphere for 3 h.
b 1 F/mol of electricity was passed through a solution of substrates (each 0.5 mmol) and Et4NBF4 (1.0 mmol) in a mixture of TFA (5 mL) and
CH2Cl2 (5 mL).
c Isolated yield after treatment of the reaction mixture with 10% NaOH (10 mL) and cetyltrimethylammonium hydroxide (0.2 mL) overnight.
1)
O2
CF3CO2H
2 HNO2
CF3CO2Na
H2O
NaNO2
HNO2
N2O3
+
+
+
in CF3CO2H–CH2Cl2
NaNO2 (0.2 equiv)
TEMPO (X equiv)
r.t. 3h
1a
3a
+
1a
H+
NO+
NO
H2O
NO2
HNO2
+
2) aq NaOH, cetyltrimethylammonium hydroxide
overnight
N2O3
N2O3
+
+
TEMPO
<1:>99
30:70
>99:<1
0 equiv
0.2 equiv
1.0 equiv
–
NO+
NO2
H+
+
HNO2
2 NO2
N2O4
+
NO2
Scheme 3 Influence of TEMPO on the O2–NaNO2 oxidation of 1a
Scheme 6 Active species generated from NaNO2 in TFA
– [e] (1F/mol)
1)
petitive reactions between 1a-c depended on the number
of bridgehead hydrogens of 1a-c, and that one equivalent
of TEMPO completely retarded the oxidation of 1a by
O2–NaNO2. On the other hand, electrochemical oxidation
of 1a was not affected by TEMPO since it proceeded with
electron-transfer mechanism.
Et4NBF4
in CF3CO2H–CH2Cl2, r.t.
TEMPO (X equiv)
3a
1a
1a
+
2) aq. NaOH, cetyltrimethylammonium hydroxide
overnight
TEMPO
51:49
51:49
52:48
0 equiv
0.2 equiv
1.0 equiv
NO may oxidize adamantyl radical to adamantyl cation
and it can be regenerated by oxygen since two equivalents
of NaNO2 were necessary to complete the oxidation of 1a
under a nitrogen atmosphere.
Scheme 4 Influence of TEMPO on electrochemical oxidation of 1a
On the basis of these results, we propose that NO works
as a hydrogen abstractor from 1a to afford adamantyl rad-
ical as an intermediate (Scheme 5)12 since it has been re-
ported that active species from NaNO2 in TFA for
aromatic nitration include NO as shown in Scheme 6,13
and NO has been known to oxidize dihydropyridine with
a hydrogen abstraction mechanism.14 This proposed
mechanism can be supported by the facts that the com-
The method presented herein is very promising from a
practical viewpoint for oxidation of adamantanes since
the reaction conditions are mild, the yields of 3a–c are
high, sodium nitrite is an economically available reagent,
and most of TFA can be recovered,15 though the solvent
effect can not be explained at present. Further application
of this method to other organic compounds than adaman-
tanes is now under investigation.
H+
NO–
O2
–
.
O2
O2
NO–
–
.
O2
HNO
NO
NO
CF3CO2H
OCOCF3
H
hydrogen abstraction
electron transfer
1a
2a
Scheme 5 Plausible reaction mechanism for oxidation of 1a by O2–NaNO2
Synlett 2006, No. 15, 2415–2418 © Thieme Stuttgart · New York

2418
O. Onomura et al.
LETTER
electrochemical oxidation: Bewick, A.; Edwards, C. J.;
Jones, S. R.; Mellor, J. M. Tetrahedron Lett. 1976, 631.
(n) By RhO3 with H2O2 in TFA: Nomura, K.; Uemura, S. J.
Chem. Soc., Chem. Commun. 1994, 129.
References
(1) (a) Geluk, H. W.; Keizer, V. G. Org. Synth., Coll. Vol. VI;
Wiley: New York, 1988, 48. (b) Krasnikov, S. V.;
Obuchova, T. A.; Yasinskii, O. A.; Balakin, K. V.
(3) Mastrorilli, P.; Nobile, C. F. Tetrahedron Lett. 1994, 35,
4193.
Tetrahedron Lett. 2004, 45, 711. (c) Lee, G. S.; Bashara, J.
N.; Sabih, G.; Oganesyan, A.; Godjoian, G.; Duong, H. M.;
Marinz, E. R.; Gutierrez, C. Org. Lett. 2004, 6, 1705.
(2) For examples, see the following: (a) By lead(IV): Jones, S.
R.; Mellor, J. M. J. Chem. Soc., Perkin Trans. 1 1976, 2576.
(b) By chromium(VI): Carlsen, P. H. J.; Kjaerstad, C.;
Aasbø, K. Acta Chem. Scand. 1995, 49, 152. (c)ByRe(VII)
with H2O2: Murray, R. W.; Iyanar, K.; Chen, J.; Wearing, J.
T. Tetrahedron Lett. 1995, 36, 6415. (d) By Ru(II) with
PhIO: Jitsukawa, K.; Oka, Y.; Einaga, H.; Masuda, H.
Tetrahedron Lett. 2001, 42, 3467. (e) By Ru(II)with TBHP:
Che, C.-M.; Cheng, K.-W.; Chan, M. C. W.; Lau, T.-C.;
Mak, C.-K. J. Org. Chem. 2000, 65, 7996. (f) By Fe(VI):
Delaude, L.; Laszlo, P. J. Org. Chem. 1996, 61, 6360.
(g) By O3: Cohen, Z.; Varkony, H.; Keinan, E.; Mazur, Y.
Org. Synth., Coll. Vol. VI; Wiley: New York, 1988, 43–47.
(h) By oxone: Kumarathasan, R.; Hunter, N. R. Org. Prep.
Proced. Int. 1991, 23, 651. (i) By dioxirane: Mello, R.;
Cassidei, L.; Fiorentino, M.; Fusco, C.; Curci, R.
(4) Perutka, J.; Martell, A. E. Anal. Chim. Acta 2001, 435, 385.
(5) Ishii, Y.; Nakayama, K.; Takeno, M.; Sakaguchi, S.;
Iwamura, T.; Nishiyama, Y. J. Org. Chem. 1995, 60, 3934.
(6) (a) Germenati, L.; Dondi, D.; Fagnoni, M.; Alibini, A.
Tetrahedron 2003, 59, 6409. (b) Ohno, T.; Mitui, T.;
Matsumura, M. J. Photochem. Photobiol., A 2003, 160, 3.
(7) Maki, S.; Konno, K.; Takayama, H. Tetrahedron Lett. 1997,
38, 7067.
(8) Neumann, R.; Dahan, M. J. Am. Chem. Soc. 1998, 120,
11969.
(9) Shinachi, S.; Matsushita, M.; Yamaguchi, K.; Mizuno, N. J.
Catal. 2005, 233, 89.
(10) Olah, G. A.; Ramaiah, P.; Rao, C. B.; Sandford, G.; Golam,
R.; Trivedi, N. J.; Olah, J. A. J. Am. Chem. Soc. 1993, 115,
7246.
(11) Dinoi, A.; Curci, R.; Carloni, P.; Damiani, E.; Stipa, P.;
Greci, L. Eur. J. Org. Chem. 1998, 871.
–
(12) The reaction course of O2 · described in Scheme 5 is under
Tetrahedron Lett. 1990, 31, 3067. (j) By oxaziridine:
DesMarteau, D. D.; Donadelli, A.; Montanari, V.; Petrv, V.
A.; Resnari, G. J. Am. Chem. Soc. 1993, 115, 4897. (k) By
DDQ: Tanemura, K.; Suzuki, T.; Nishida, Y.;
Satsumabayashi, K.; Horaguchi, T. J. Chem. Soc., Perkin
Trans. 1 2001, 3230. (l) By MCPBA: Takaishi, N.;
Fujikura, Y.; Inamoto, Y. Synthesis 1983, 293. (m) By
investigation.
(13) Uemura, S.; Toshimitsu, A.; Okano, M. J. Chem. Soc.,
Perkin Trans. 1 1978, 1076.
(14) Ito, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A.
J. Org. Chem. 1997, 62, 3582.
(15) Spitzer, U. A.; Stewart, R. J. Org. Chem. 1974, 39, 3936.
Synlett 2006, No. 15, 2415–2418 © Thieme Stuttgart · New York