Oxidative decarboxylation of 2-aryl carboxylic acids using (Diacetoxyiodo)benzene for preparation of aryl aldehydes, ketones, and nitriles

Article abstract of DOI:10.1055/s-0030-1258812

A novel synthetic application of the hypervalent iodine reagent, (diacetoxyiodo)benzene, and catalytic amount of sodium azide in acetonitrile for oxidative decarboxylation of 2-aryl carboxylic acids into corresponding aldehydes, ketones, and nitriles at room temperature is described. The advantages of this protocol are shorter reaction times and mild reaction conditions to obtain moderate to good yields.

Full text of DOI:10.1055/s-0030-1258812

2
778
LETTER
Oxidative Decarboxylation of 2-Aryl Carboxylic Acids Using
Diacetoxyiodo)benzene for Preparation of Aryl Aldehydes, Ketones,
and Nitriles
(
O
V
xidative Decarbo
i
xylatio
k
n of 2-Aryl
a
sA cids N. Telvekar,* Kulbhushan A. Sasane
Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
Fax +91(22)24145614; E-mail: vikastelvekar@rediffmail.com
Received 19 July 2010
obtained by these reactions, however, are only moderate.
Abstract: A novel synthetic application of the hypervalent iodine
reagent, (diacetoxyiodo)benzene, and catalytic amount of sodium
azide in acetonitrile for oxidative decarboxylation of 2-aryl carbox-
Although the oxidation of a-amino acids with chlor-
1
3
amine-T usually gave nitriles in good yields, the method
ylic acids into corresponding aldehydes, ketones, and nitriles at suffers a disadvantage that the corresponding aldehydes
room temperature is described. The advantages of this protocol are are produced as by products. Recently tert-butoxycop-
shorter reaction times and mild reaction conditions to obtain mod- per(II) bromide, generated in situ from copper bromide
erate to good yields
and lithium tert-butoxide, has been used for nitrile forma-
Key words: (diacetoxyiodo)benzene, decarboxylation, aldehydes, tion,14 and trichloroisocyanuric acid in methanol in the
ketones, nitriles
1
5
presence of pyridine has also been used. However, in
spite of the many reagents available there is still scope for
an improved reagent system.
Hypervalent iodine reagents have attracted increasing in-
terest during the last decade because of their selective,
mild, and environmentally friendly properties as oxidiz-
ing agents in organic synthesis. Investigations from our
laboratories have revealed a series of new paradigms for
hypervalent iodine mediated reactions under mild condi-
For our initial studies, phenyl acetic acid was chosen as a
model substrate. A mixture of phenyl acetic acid, (diacet-
oxyiodo)benzene, and a catalytic amount of sodium azide
in anhydrous dichloromethane was stirred at room tem-
perature. After completion and workup of reaction, benz-
aldehyde was isolated in 88% yield by using silica gel
chromatography.
1
tions.
(
Diacetoxyiodo)benzene is a trivalent iodine reagent
In the absence of sodium azide reaction does not take
place. Further screening for the reaction conditions re-
vealed that, acetonitrile and chloroform were also suitable
solvents for this conversion (Scheme 1).
which is readily available and frequently used in several
oxidative transformations. We observed that this reagent
could be used with catalytic amount of sodium azide for
oxidative decarboxylation of carboxylic acids to corre-
sponding aldehydes and ketones, while a-amino acids are
converted to nitriles.
2
CHO
COOH
DIB, cat. NaN3
MeCN, 20 min
Oxidative decarboxylation of a-hydroxy acids to alde-
hydes or ketones can be achieved with various oxidizing
agents, such as chromic acid, sodium bismuthate, lead
tetraacetate, nickel peroxide, periodate, and N-
iodosuccinimide but, in the absence of the a-hydroxy
group, there are only few systems available for decarbox-
ylation of simple carboxylic acids to aldehydes and ke-
tones, such as tetrabutylammonium periodate, sodium
periodate in combination with polystyrene-bound
Mn(T4PyP) or iron and manganese tetraphenylporphy-
0
°C to r.t.
Scheme 1 Oxidative decarboxylation of phenyl acetic acid using
diacetoxyiodo)benzene and catalytic sodium azide
3
4
(
5
6
7
8
It was interesting to observe that, under similar reaction
conditions, 2-phenylpropanoic acid and a-amino(phe-
nyl)acetic acid were successfully converted into 1-phe-
nylethanone and benzonitrile, respectively (Scheme 2).
9
1
0
Me
Me
rins. In connection with oxidative decarboxylation of a-
amino acids, it was reported the lead tetraacetate oxida-
tion of their N-acyl derivatives gave N-acylimines which
COOH
DIB, cat. NaN3
O
MeCN, 20 min
0 °C to r.t.
5
were hydrolyzed to the corresponding aldehydes. As far
as the transformation into nitriles is concerned, N-bromo-
NH2
COOH
1
1
12
succinimide, and alkaline bromine
have been em-
CN
ployed as oxidizing agents. The isolated yields of nitriles
DIB, cat. NaN3
MeCN, 60 min, r.t.
SYNLETT 2010, No. 18, pp 2778–2780
Advanced online publication: 08.10.2010
DOI: 10.1055/s-0030-1258812; Art ID: D19210ST
x
x
.x
x
.2
0
1
0
Scheme 2 Ketone and nitrile by decarboxylation using (diacet-
oxyiodo)benzene and catalytic sodium azide
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Decarboxylation of 2-Aryl Carboxylic Acids
2779
Whilst we observed that (diacetoxyiodo)benzene alone is Table 1 Decarboxylation of 2-Aryl Carboxylic Acids Using (Diac-
a
etoxyiodo)benzene (continued)
inactive, it has been reported that, with a-amino aryl car-
boxylic acids, in situ generation of PhI(OCH ) using (di-
3
2
Entry Substrate
Product
Time Yield
acetoxyiodo)benzene and KOH in methanol can used for
nitrile formation, but low yields were reported, and the
method works only for p-hydroxyaryl substrates.16
b
(
min) (%)
CHO
CHO
COOH
COOH
7
25 90
To explore the possibility of using other hypervalent io-
dine reagents we carried out all the above reactions using
a catalytic amount of sodium azide and hypervalent iodine
O2N
O2N
8
20 87
30 90
reagents such as IBX, KIO , and 4,4¢- bis(dichlor-
3
oiodo)biphenyl in place of the (diacetoxyiodo)benzene,
but no formation of benzaldehyde, ketone, and nitrile was
observed even after long reaction times.
OH
COOH
CHO
O
9
0
1
2
3
4
5
In order to explore the scope of reaction, a variety of sub-
stituted carboxylic acid compounds was converted into
corresponding aldehydes, ketones, and nitriles by oxida-
tive decarboxylation in good to excellent yields, and the
COOH
1
1
1
1
1
1
20 85
20 85
15 90
60 90
60 86
55 85
1
7,18
results are summarized in Table 1.
It was found that
both electron-rich and electron-deficient aromatic carbox-
ylic acids were successfully converted into their corre-
sponding aldehydes (Table 1, entries 2–7). It was noted
that under these reaction conditions methoxy and ester
groups remain unaffected (Table 1, entries 2, 3, 6). a-Hy-
droxyphenylacetic acid, 2-phenylpropanoic acid and 2-
phenylbutanoic acid were readily converted into benzal-
dehyde, 1-phenylethanone and 1-phenylpropan-1-one, re-
spectively (Table 1, entries 9–11). a-Aminophenylacetic
acid, a-amino(4-chlorophenyl)acetic acid, and a-ami-
no(naphthalen-2-yl)acetic acid were successfully convert-
ed into the corresponding nitriles in moderate to good
yields (Table 1, entries 13–15). No reaction was observed
when aliphatic carboxylic acids were subjected to these
reaction conditions (Table 1, entries 16–18).
COOH
COOH
NH2
O
O
CN
COOH
NH2
COOH
CN
Cl
Cl
Table 1 Decarboxylation of 2-Aryl Carboxylic Acids Using (Diac-
NH2
COOH
etoxyiodo)benzenea
CN
Entry Substrate
1
Product
Time Yield
b
(
min) (%)
1
1
6
7
–
–
120 n.r.c
120 n.r.c
COOH
COOH
CHO
COOH
20 88
15 85
15 89
20 85
20 85
25 88
Me
CHO
COOH
COOH
NH2
2
120 n.r.c
1
8
–
MeO
COOH
MeO
MeO
MeO
CHO
OMe
a
Reaction conditions: substrate (1 equiv), (diacetoxyiodo)benzene
1.5 equiv), and catalytic NaN (0.12 equiv) in MeCN (10 mL).
Isolated yields after column chromatography and structures were
confirmed by comparison of IR and H NMR with authentic materi-
als.
3
(
3
b
OMe
COOH
1
CHO
Cl
4
c
No reaction.
Cl
CHO
COOH
In summary, we have presented a novel application of (di-
acetoxyiodo)benzene for oxidative decarboxylation of 2-
arylcarboxylic acids to aldehydes, ketones, and nitriles at
room temperature. The method developed is mild and
gives moderate to good yields.
5
Cl
Cl
CHO
COOH
6
EtOOC
EtOOC
Synlett 2010, No. 18, 2778–2780 © Thieme Stuttgart · New York

2
780
V. N. Telvekar, K. A. Sasane
LETTER
Acknowledgment
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K.A.S. thanks CSIR (New Delhi) for the award of a fellowship.
(
(
(
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(
(
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17) Representative Procedure for Decarboxylation of
(
1) (a) Telvekar, V. N.; Takale, B. Tetrahedron Lett. 2010, 49,
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(
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(
Diacetoxyiodo)benzene (1.5 equiv) and NaN (0.12 equiv)
6
(
3
in MeCN (10 mL) were stirred at 0 °C for 2 min, then phenyl
acetic acid (1 equiv) was added to the stirred solution. The
reaction mixture was allowed to come at r.t. and stirring
continued until completion of reaction (TLC), when it was
(
Zhdankin, V. V. Tetrahedron Lett. 2006, 47, 6305.
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quenched with H O (25 mL) and extracted with CHCl
(
(
(
(
2
3
(
3 × 10 mL). The combined organic layers were washed with
dilute NaHCO (20 mL), followed by H O (3 × 20 mL),
dried over Na SO , and concentrated in vacuo. The residue
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2
2
4
was purified by column chromatography on silica gel
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1
964, 12, 403.
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(
(
(
colorless liquid.
5
(
18) Representative Procedure for Decarboxylation of
a-Amino(phenyl)acetic Acid (Table 1, Entry 13)
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(
Diacetoxyiodo)benzene (1.5 equiv) and NaN (0.12 equiv)
3
in MeCN (10 mL) were stirred at r.t. for 2 min, then a-amino-
phenyl)acetic acid (1 equiv) was added to the stirred
solution. Stirring was continued until completion of reaction
TLC), when it was quenched with H O (25 mL) and worked
(
9) Santaniello, E.; Ponti, F.; Manzocchi, A. Tetrahedron Lett.
(
1
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(
(
(
1
2
up as mentioned above to yield benzonitrile (90%) as a
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–
1 13
1
1
682, 1572, 1492 cm . C NMR (75 MHz, CDCl ): d =
3
32.84, 132.10, 129.21, 118.82, 112.41.
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Synlett 2010, No. 18, 2778–2780 © Thieme Stuttgart · New York

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