Acceleration of Norrish Type I reaction with molecular oxygen and catalytic CBr4

Article abstract of DOI:10.1055/s-0029-1217524

We report a useful method for facile synthesis of aryl carboxylic acids from aryl ketones by aerobic photooxidation using the inexpensive and easily handled CBr₄ as catalyst. This procedure is applicable to inert compounds under usual photo-irradiation conditions, and appears very attractive from the view point of new method of expansion of Norrish Type I reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217524

LETTER
2017
Acceleration of Norrish Type I Reaction with Molecular Oxygen and Catalytic
CBr4
A
S
ccelerationo
h
f
N
orrishTy
i
pe
I
Re
n
action -ichi Hirashima, Tomoya Nobuta, Norihiro Tada, Akichika Itoh*
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
Fax +81(58)2378573; E-mail: itoha@gifu-pu.ac.jp
Received 5 March 2009
conditions is generally known as the Norrish Type I reac-
tion; however, this reaction is inert when using aryl ke-
tones, such as acetophenone, as starting material because
Abstract: We report a useful method for facile synthesis of aryl
carboxylic acids from aryl ketones by aerobic photooxidation using
4
the inexpensive and easily handled CBr as catalyst. This procedure
4
is applicable to inert compounds under usual photo-irradiation con- of its low excitation energy and instability of the phenyl
ditions, and appears very attractive from the view point of new and primary alkyl radical species, which will be generated
by a-cleavage. However our method seems applicable to
Key words: Norrish Type I, photooxidation, carbon tetrabromide, a wider range of substrates than that under usual Norrish
method of expansion of Norrish Type I reaction.
aerobic, carboxylic acid
Table 1 Study of Reaction Conditions for Aerobic Photooxidation
O
O2, hν (400 W Hg lamp)
Functionalized aromatic carboxylic acids are widely used
as key intermediates of pharmaceutical chemicals and as
monomers of special polymers. Although several groups
reported the syntheses of these aromatic carboxylic acids
from aryl methyl ketones, these oxidation reactions either
essentially involve the use of large quantities of heavy
metals and complex organic compounds under strongly
CO2H
bromo source
solvent (5 mL)
1
a (0.3 mmol)
2a
Entry Bromo source Amount Solvent
(equiv)
Time
(h)
Yield of 2a
(%)a
1
1
2
3
4
5
6
7
8
9
0
CBr
4
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.3
0.2
hexane
PhH
10
10
10
10
10
10
10
10
10
12
12
12
10
10
10
10
10
10
10
trace
trace
12
basic conditions or result in modest yields. Due to an in-
creasing demand for more environmentally benign syn-
thesis, molecular oxygen has received much attention as
an ultimate oxidant, since it, theoretically, produces only
water with a certain suitable catalyst, is rather inexpensive2
and of larger atom efficiency than that of other oxidants.
With these perspectives, we have examined a new oxida-
tion method with molecular oxygen and found direct aer-
obic photooxidation of methyl groups at the aromatic
nucleus and primary alcohols to the corresponding car-
boxylic acids in good yields in the presence of a catalytic
CBr4
CBr4
CBr4
CH Cl
2
2
MeCN
12
CBr4
i-Pr O
2
14
CBr4
MeOH
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
30
CBr4
73
CBr4
37
3
amount of the bromo source. Our method is interesting in
terms of use of molecular oxygen, heavy-metal-free waste
reduction, inexpensive acquisition of reagents, and envi-
ronmentally low-impact solvent, and, in the course of our
further study of this photooxidation, we also found that 11
aryl methyl ketones were oxidized to aromatic carboxylic
CBr
4
27
1
CBr4
–
82
0
1
1
1
1
1
2
3
4
5
6
CBr4
CBr4
Br2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0b
acids successfully under similar conditions (Scheme 1).
0c
O
O
O2, cat. CBr4, hν
20
Ar
Me
Ar
OH
aq HBr
LiBr
26
Scheme 1
trace
0
A cleavage of the bond between carbonyl group and a- 17
carbon of carbonyl compound under photo-irradiation
MgBr ·OEt
2 2
18
BrCCl3
NBS
22
1
9
trace
SYNLETT 2009, No. 12, pp 2017–2019
Advanced online publication: 01.07.2009
DOI: 10.1055/s-0029-1217524; Art ID: U02609ST
x
x
.x
x
.2
0
0
9
a
b
c
All yields are for pure, isolated products.
The reaction was carried out in the dark.
The reaction was carried out under Ar.
©
Georg Thieme Verlag Stuttgart · New York

2
018
S.-i. Hirashima et al.
LETTER
Type I reaction conditions. Herein, we describe the de- volves abstraction of hydrogen radical from aryl alkyl
tailed study of our improvement of the conventional Nor- ketone with bromo radical, generated from CBr , to pro-
4
rish Type I reaction conditions.
duce phenacyl radical 3. Positive evidence remains elu-
sive; however, we think there are two paths, a and b,
which involve cleavage of carbon–carbon bond of phen-
acyl bromide 4 and 1,2-diketone 8 correspondingly. Be-
cause of the stability of its generated radical species, 8%
and 37% of 2a were obtained correspondingly when using
Table 1 shows the results of the study of the reaction con-
ditions for aerobic photooxidation using acetophenone
6
7
5
(
1a) as test substrate. Among our data, better results were
obtained when using 0.2 equivalents of CBr as bromo
source and EtOAc as solvent (entries 1–10 and 14–19).
The fact that benzoic acid (2a) was not obtained without
4
1
(
2
g and 1h under the usual Norrish reaction condition
Table 2, entries 7 and 8). Compounds 1h and 1j produced
a and 2j correspondingly in lower yield due to its steric
CBr , irradiation or molecular oxygen shows the necessity
4
of all for this reaction (entries 11–13).
hindrance and formation of many unidentified products.
Table 2 presents the scope and limitation of this oxidation
under the optimized reaction conditions mentioned above.
The corresponding carboxylic acids were obtained in
good to better yield regardless of an electron-donating or
electron-withdrawing group at aromatic nucleus (entries
In conclusion, we report a useful method for facile synthe-
sis of aryl carboxylic acids from aryl ketones by aerobic
photooxidation using inexpensive and easily handled
CBr as catalyst. This procedure is applicable to inert
4
compounds under usual photo-irradiation conditions, and
appears very attractive from the view point of new method
of expansion of Norrish Type I reaction. Further studies
on use of the bromo source catalyst and additional appli-
cations are now in progress in our laboratory.
1
(
–5). Moreover, propiophenone (1f), isobutyrophenone
1g), and 2,2-dimethylpropiophenone (1h) were oxidized
to benzoic acid (2a) in good to moderate yields (entries 6–
). We also found that a-phenethyl alcohol (1i) was oxi-
8
dized directly to 2a in 73% yield; however, 2-naphthoic
acid was obtained in low yield when using 2-naphthophe-
none (1j) as starting material (entries 9 and 10). Since the
corresponding carboxylic acids were not obtained or ob-
tained only in low yield when using 1a, 1f, and 1g as sub-
strates under usual Norrish Type I reaction conditions,
only photo-irradiation, our procedure is complementary to
conventional Norrish Type I reaction.
References and Notes
(
1) (a) Kajigaeshi, S.; Nakagawa, T.; Nagasaki, N.; Fujisaki, S.
Synthesis 1985, 674. (b) Moriarty, R. M.; Prakash, I.;
Penmasta, R. J. Chem. Soc., Chem. Commun. 1987, 202.
(
c) Olah, G. A.; Ramos, M. T.; Wang, Q.; Surya Prakash,
G. K. Synlett 1991, 41. (d) Kathó, A.; Beck, M. T. Synlett
992, 165. (e) Gurunath, S.; Sudalai, A. Synlett 1999, 559.
1
The detailed mechanism has not been clarified yet; as
shown in Scheme 2, we infer the corresponding carboxy-
lic acid was produced via acyl radical 5. The first step in-
(
(
f) Zabjek, A.; Petriè, A. Tetrahedron Lett. 1999, 40, 6077.
g) Minisci, F.; Recupero, F.; Fontana, F.; Bjørsvik, H. R.;
Liguori, L. Synlett 2002, 610.
Table 2 Aerobic Photooxidation of Aryl Alkyl Ketones
O2, hν (400 W Hg lamp)
substrate
CBr4 (0.2 equiv)
product
(
0.3 mmol)
EtOAc (5 mL)
Entry
Substrate
Time (h)
Product, yield (%)a
1
2
3
4
5
1a R = H
12
12
12
12
24
2a 82
2b 79
2c 87
2d 83
2e 88
O
1b R = t-Bu
1c R = OMe
1d R = Cl
1e R = CN
CO2H
R
R
O
6
7
8
1f R = Et
1g R = i-Pr
1h R = t-Bu
18
12
12
2a 66
2a 77 (8)
2a 39 (37)
b
R
b
OH
9
1i
1j
12
12
2a 73
O
CO2H
1
0
2j 20
a
All yields are for pure, isolated products.
The reaction was carried out without CBr4.
b
Synlett 2009, No. 12, 2017–2019 © Thieme Stuttgart · New York

LETTER
Acceleration of Norrish Type I Reaction
2019
hν
(2) For example, see: Lenoir, D. Angew. Chem. Int. Ed. 2006,
5, 3206; and references cited therein.
(3) (a) Itoh, A.; Hashimoto, S.; Kodama, T.; Masaki, Y. Synlett
1
)
)
CBr4
O
Br
+
CBr3
4
2005, 2107. (b) Itoh, A.; Hashimoto, S.; Masaki, Y. Synlett
2005, 2639. (c) Hirashima, S.; Itoh, A. Synthesis 2006,
1757. (d) Hirashima, S.; Hashimoto, S.; Masaki, Y.; Itoh, A.
2
R
Ar
Br
Tetrahedron 2006, 62, 7887. (e) Hirashima, S.; Itoh, A.
Photochem. Photobiol. Sci. 2007, 6, 521. (f) Hirashima, S.;
Itoh, A. Green Chem. 2007, 9, 318. (g) Hirashima, S.; Itoh,
A. J. Synth. Org. Chem. Jpn. 2008, 66, 748.
(4) Norrish, R. G. W.; Bamford, C. H. Nature (London) 1936,
138, 1016.
HBr
solvent
O
O
7
O2
or
O
H
O
HBr
R
O
R
R
R
Ar
Ar
Ar
Ar
Ar
O
3
6
OH
H2O
R
Br
Br
path b
(5) Typical Procedure
A solution of acetophenone (1a, 0.3 mmol) and CBr (0.06
4
O
mmol) in dry EtOAc (5 mL) in a pyrex test tube, purged with
O
path a
an O balloon, was stirred and irradiated externally with a
2
400 W high-pressure mercury lamp for 12 h. The reaction
4
mixture was concentrated in vacuo, and 10% NaOH aq
solution was added. The aqueous solution was washed with
O
8
hν
hν
BrCHR
Et O, and then acidified with 2 N HCl aq solution, which
2
was extracted with Et O. The organic layer was washed with
O
O
R
2
brine and dried over MgSO , and concentrated in vacuo. The
4
Ar
product was pure without further purification.
5
(
6) 4-Bromobenzoic acid was obtained in 82% yield when the
reaction was carried out using p-bromophenacyl bromide as
O2
solvent
or
substrate without CBr under photo-irradiation.
4
HBr
hν
(
7) Benzoic acid was obtained in 76% and 48% yield
correspondingly when the reaction was carried out using
phenylglyoxal and benzil as substrate under these reaction
conditions.
Ar CO3
Ar CO3H
Ar CO2H
9
10
11
solvent
or
HBr
O
OH
O
O
O2
3)
BrCHR
BrCHR
BrCHR
H2O
O
hν
BrCR
Br
+
RCO
Scheme 2 Plausible path of aerobic photooxidation of aryl methyl
ketones
Synlett 2009, No. 12, 2017–2019 © Thieme Stuttgart · New York

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