Photolytic decarboxylation of α-arylcarboxylic acids mediated by HgF2 under a dioxygen atmosphere

Article abstract of DOI:10.1016/j.tetlet.2006.01.082

Mercuric fluoride (HgF₂), as a light-sensitive inorganic compound, in the presence of dioxygen is able to convert various α-aryl- and α,α-diarylcarboxylic acids into the corresponding aldehydes and ketones selectively under photoirradiation via trapping of the benzylic radical by O₂.

Full text of DOI:10.1016/j.tetlet.2006.01.082

Tetrahedron Letters 47 (2006) 1965–1968
Photolytic decarboxylation of a-arylcarboxylic acids mediated by
HgF2 under a dioxygen atmosphere
Saeid Farhadi,a,* Parisa Zaringhadama and Reza Zarei Sahamiehb
aDepartment of Chemistry, University of Lorestan, Lorestan, Khoramabad 68135-465, Iran
bFaculty of Science, University of Lorestan, Lorestan, Khoramabad 68135-465, Iran
Received 29 September 2005; revised 4 January 2006; accepted 16 January 2006
Abstract—Mercuric fluoride (HgF2), as a light-sensitive inorganic compound, in the presence of dioxygen is able to convert various
a-aryl- and a,a-diarylcarboxylic acids into the corresponding aldehydes and ketones selectively under photoirradiation via trapping
of the benzylic radical by O2.
Ó 2006 Elsevier Ltd. All rights reserved.
Among the various carboxylic acids, decarboxylation of
a-arylcarboxylic acids and their salts has received a
good deal of attention, especially since several nonste-
roidal anti-inflammatory drugs (NSAIDs), for example,
ketoprofen and ibuprofen, are a-arylpropionate salts.1–3
Indeed, decarboxylation of these acids provides a ben-
zylic moiety, which is capable of stabilizing an incipient
ionic or radical intermediate.
prepare radical intermediates and organic compounds
such as cyclophanes, the syntheses of which are difficult
using conventional methods.18–21 PD is also important
in pharmaceuticals22–25 and agriculture,26,27 as many
drugs, herbicides and pesticides containing the –COOH
groups can extrude CO2 when exposed to sunlight pro-
ducing potentially toxic materials. PD is also the basis
of the photo-Kolbe reaction.28 The PD of a-arylcarb-
oxylic acids thus continues to be an area of active
research interest.29–32
In this context, thermal decarboxylation of various a-
arylcarboxylic acids has been extensively investigated
for the transformation of these acids to aldehydes or
ketones, alcohols and arylalkanes by using metallic
and nonmetallic oxidants including (NH4)2Ce(NO3)6,4
Co(OAc)3,5 NaClO,6 n-Bu4NIO4,7 K2S2O8–AgNO3,8
CuI–O2,9 Fe(TPP)(X)–PhIO,10 NaIO4-crown ethers,11,12
In continuation of this work, we decided to examine
photolysis of a-aryl acids in the presence of mercuric
halides (HgX2, X = F, Cl, Br and I) under an oxygen
atmosphere. Herein, we report results obtained on PD
of various a-aryl- and a,a-diarylcarboxylic acids using
HgF2 in CH3CN under a dioxygen atmosphere at room
temperature which resulted in the formation of the cor-
responding aldehydes and ketones in good yields.
Mn(OAc)3 and KO2–nitrobenzenesulfonyl chloride.14
13
Also, photolytic decarboxylation (PD) reactions of aryl-
acetic acids and their derivatives have been extensively
reported in the presence of various electron acceptors
or photosensitizers such as aza aromatic compounds,
dicyanonaphthalene, tetracyanobenzene and hetero-
cyclic N-oxides.15–17
In initial experimental studies on photoirradiation of
a-aryl acids in the presence of inorganic mercury
compounds, we found that illumination of a CH3CN
solution of diphenylacetic acid and HgF2 with a 400
W high pressure mercury lamp under oxygen for 1 day,
gave benzophenone in 95% yield along with elemental
mercury, carbon dioxide (the limewater test) and HF,
while the use of HgCl2, HgBr2, HgI2, Hg2Cl2 and also
Hg(NO3)2 instead of HgF2, did not initiate the reaction.
While other mercuric halides are less- or nonphotosensi-
tive, the high sensitivity of HgF2 to light is well known.33
Without irradiation, benzophenone was scarcely
PD is important in several areas of study. In synthetic
organic chemistry, several groups have utilized PD to
Keywords: a-Arylcarboxylic acids; Photolytic; Decarboxylation;
Mercuric fluoride; Carbonyl compounds.
*
Corresponding author. Fax: +98 6614600088; e-mail: sfarhad2001@
yahoo.com
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.082

1966
S. Farhadi et al. / Tetrahedron Letters 47 (2006) 1965–1968
obtained even in the presence of HgF2. Therefore, we
concluded that high sensitivity of HgF2 to light plays
an important role in this process. This reagent, that is
not a decarboxylating agent in the absence of light,
can probably be activated photochemically, affording
selectively decarboxylated product. The formation of
appreciable amounts of elemental Hg and carbon diox-
ide in the course of the reaction support suggestion that
the present photoreaction involves a photoinduced one-
electron transfer from the carboxylate moiety (–COOH)
to HgF2.34 In addition to HgF2, oxygen proved to be an
oxidizing reagent in this reaction and, in the absence of
this reagent (under N2), a dimeric product was observed
instead of the corresponding carbonyl product, as the
only product, in excellent yield (see below).
To evaluate the scope of this method, the decarboxyl-
ation of various a-arylcarboxylic acids, in which their
a-carbon atom is attached to an aryl group were studied.
The results for PD of various aryl acids are summarized
in Table 1. As can be seen in Table 1, all of the a-aryl
acids decarboxylated selectively to give the correspond-
ing carbonyl compounds under our reaction conditions.
In all cases, in addition to the corresponding carbonyl
compounds, large amounts of Hg, CO2 and HF were
formed during irradiation.
Table 1. Photolytic decarboxylation of a-aryl acids using HgF2 under an O2 atmosphere
HgF2 O2
CH3CN
hv
r.t
Ar
Product
Producta
C(X)(Y)COOH
Entry
Ar
X
Y
Yieldb (%)
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OH
H
H
H
H
H
H
H
H
H
H
H
H
C6H5CHO
4-MeC6H4CHO
2-MeC6H4CHO
4-MeOC6H4CHO
2-MeOC6H4CHO
3-MeOC6H4CHO
4-NO2C6H4CHO
4-FC6H4CHO
4-HOC6H4CHO
2-ClC6H4CHO
4-ClC6H4CHO
2,4-Cl2C6H3CHO
2,6-Cl2C6H3CHO
1-C10H7CHO
2-C10H7CHO
4-PhC6H4CHO
78
88
85
88
84
82
65
60
72
70
78
80
76
74
70
66
95
94
94
91
95
96
98
88
78
93
79
97
66
84
74
72
70
78
76
75
78
75
4-MeC6H4
2-MeC6H4
4-MeOC6H4
2-MeOC6H4
3-MeOC6H4
4-NO2C6H4
4-FC6H4
4-HOC6H4
2-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
1-C10H7
2-C10H7
4-PhC6H4
C6H5
C6H5
C6H5
C6H5
4-ClC6H4
4-ClC6H4
4-MeOC6H4
4-iso-BuC6H4
6-MeO-2-C10H6
C6H5
9
10
11
12
13
14c
15c
16
17
18
19
20
21
22
23
24d
25e
26
27
28f
29
30
31
32
33
34
35
36
37g
38g
C6H5
CH3
C2H5
n-C3H7
C6H5
4-ClC6H4
4-MeOC6H4
CH3
CH3
C6H5
OH
C6H5
H
H
H
H
H
(C6H5)2C@O
C6H5(CH3)C@O
C6H5(C2H5)C@O
C6H5(n-C3H7)C@O
4-ClC6H4(C6H5)C@O
(4-ClC6H4)2C@O
(4-MeOC6H4)2C@O
(4-iso-BuC6H4)(CH3)C@O
(6-MeO-2-C10H6)(CH3)C@O
(C6H5)2C@O
C6H5
C6H5
C6H5COOH
(C6H5)2C@O
4-CNC6H4CHO
4-CNC6H4
4-Me2NC6H4
4-(Me2NCO)C6H4
4-(CHO)C6H4
4-(MeCO)C6H4
4-(MeO2CCH2)C6H4
4-(EtO2CCH2)C6H4
4-AcOC6H4
4-TBDMS–OC6H4
4-TMS–OC6H4
4-Me2NC6H4CHO
4-(Me2NCO)C6H4CHO
4-(CHO)C6H4CHO
4-(MeCO)C6H4CHO
4-(MeO2CCH2)C6H4CHO
4-(EtO2CCH2)C6H4CHO
4-AcOC6H4CHO
4-TBDMS–OC6H4CHO
4-TMS–OC6H4CHO
H
H
H
H
H
a All products were characterized on the basis of mass, IR and 1H NMR spectral data and comparison with data reported in the literature.
b Yields are for isolated products.
c 1-C10H7 and 2-C10H7 are 1-naphthyl and 2-naphthyl, respectively.
d Ibuprofen = 2-(p-iso-buthylphenyl)propionic acid.
e Naproxen = 2-(6-methoxy-2-naphthyl)propionic acid.
f Sodium salt of diphenylacetic acid.
g TBDMS and TMS are tert-BuMe2Si- and Me3Si-protecting groups, respectively.

S. Farhadi et al. / Tetrahedron Letters 47 (2006) 1965–1968
Hg
1967
Phenylacetic acids having electron-donating groups on
H
HgF
2
under O2
hv
their phenyl ring, for example, Me and OMe groups,
were converted into the corresponding benzaldehydes
in excellent yields (entries 2–6) while 4-nitro- and 4-flu-
orophenylacetic acids which possess an electron-with-
drawing group were less reactive (entries 7 and 8).
Other ring-substituted phenylacetic acids and arylacetic
acids gave the corresponding aldehydes in moderate to
high yields (entries 9–16). Various secondary a-aryl
and a,a-diaryl acids were also converted with high selec-
tivity to the corresponding ketones with yields better
than the primary a-aryl acids (entries 17–25). Benzilic
and mandelic acids, which are a-hydroxyarylacetic
acids, gave benzophenone and benzoic acid, respec-
tively, under the reaction conditions (entries 26 and 27).
.
COOH
2
2
CH
CHCOOH
2
2
H-abstraction
-CO2,
-2HF
1b
2b
1a
-H2O
C=O
1
under N2
CH-CH
2a
Scheme 1. A plausible photoreaction pathway for decarboxylation of
diphenylacetic acid.
The generation of 1b during the photoreaction was con-
firmed by a positive KI–starch test on the photolysate.
This test provided evidence for involvement of the benz-
ylic radical intermediates 1a, which are highly reactive
towards O2.
Whereas a-aryl acids were decarboxylated in an efficient
way, aliphatic acids, benzoic acid and arylcarboxylic
acids such as 3-phenylpropionic and 3,3-diphenylprop-
ionic acids, which possess no aryl group at the a-posi-
tion, were inert under the reaction conditions, and
only the starting materials were recovered quantitatively
even after 2 days of irradiation. It is noteworthy to men-
tion here that in contrast to methyl diphenylacetate,
which was inert towards PD, the sodium diphenylace-
tate salt was decarboxylated efficiently (entry 28). More-
over, the method is compatible with common
functionalities such as cyano (entry 29), tert-amino
(entry 30), N,N-dimethylamido (entry 31), aldehyde
and ketone (entries 32 and 33), and esters (entries 34
and 35) groups. Furthermore, common O-protecting
groups such as acyl (entry 36) and silylethers (entries
37 and 38) remain unchanged during oxidation.
In conclusion, we have developed a new and efficient
method for PD of arylacetic acids by the use of HgF2,
as an inorganic photooxidant. This reaction is an inter-
esting example of the application of PD in the transfor-
mation of arylacetic acids to carbonyl compounds. It is
suggested that arylacetic acids are decarboxylated via a
radical pathway although the exact role of HgF2 in the
generation of radical intermediates is not yet known.
Studies on a more detailed mechanism and applications
to other substrates are now in progress in our
laboratory.
General procedure for photolysis of a-arylcarboxylic
acids: To a solution of 1 mmol of each a-aryl acid in
25 mL of acetonitrile in a Pyrex flask containing a Tef-
lon-coated magnet bar was added 1 mmol of HgF2.
Oxygen was passed through the mixture which were
kept under an oxygen atmosphere (O2 balloon). It was
then placed in a water bath with the temperature
adjusted to 25 2 °C. The mixture was magnetically
stirred and irradiated. During the course of the reaction
a grey precipitate of mercury was formed. The photo-
reaction was followed by TLC and, after 1 day (24 h)
which the mixture darkened completely, the irradiation
was stopped and the precipitate was filtered off. The
filtrate was concentrated on a rotary evaporator under
a reduced pressure at room temperature and the residue
was subjected to silica gel plate or column chromato-
graphy using carbon tetrachloride–diethyl ether as
eluent. Yields are shown in Table 1. All of carbonyl
products obtained were characterized by MS, 1H
NMR and IR spectra and by comparison with known
compounds.
In an attempt to detect intermediates and to clarify the
reaction pathway, the photolysis of diphenylacetic acid
was carried out under the conditions outlined above,
except in nitrogen—rather than oxygen-saturated solu-
tion which resulted in the formation of 1,1,2,2-tetra-
phenylethane in 92% yield as the only photoproduct.
For further confirmation, phenylacetic acid and 4-meth-
ylphenylacetic acid were allowed to react under the same
conditions as diphenylacetic acid and were found to
give 1,2-diphenylethane (80%) and 1,2-di(4-methylphen-
yl)ethane (86%), respectively, similar to the result
obtained for diphenylacetic acid. Clearly, the formation
of these dimeric photoproducts under an inert atmo-
sphere is attributed to coupling of the corresponding
benzylic radicals.
Therefore, although the mechanism of this reaction is
not yet clear and intermediates have not been observed
directly, the formation of dimeric products under N2
indicates that benzylic radicals are possible intermedi-
ates. A plausible reaction pathway is shown in Scheme
1 using diphenylacetic acid 1 as the prototype. Under
an O2 atmosphere, the benzylic radical intermediate 1a
trapped by O2 and forms the corresponding hydroper-
oxide 1b. The intermediate 1b is known to eliminate
H2O readily to give the corresponding carbonyl com-
pound 2b.3,14,35 Under an inert atmosphere (N2 gas),
the dimeric product 2a is formed via homocoupling
of 1a.
Acknowledgements
This work was supported by the University of Lorestan
Research Council.
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