A novel system for decarboxylative bromination

Article abstract of DOI:10.1016/j.tetlet.2007.04.137

A simple and mild method for decarboxylative bromination of α,β-unsaturated carboxylic acids has been developed using diphosphorus tetraiodide in combination with tetraethylammonium bromide (TEAB) at room temperature. High yields of the corresponding bromoalkenes were obtained.

Full text of DOI:10.1016/j.tetlet.2007.04.137

Tetrahedron Letters 48 (2007) 4529–4532
A novel system for decarboxylative bromination
*
Vikas N. Telvekar and Somsundaram N. Chettiar
Department of Pharmaceutical Sciences and Technology, University Institute of Chemical Technology,
Matunga, Mumbai 400 019, India
Received 12 March 2007; revised 13 April 2007; accepted 27 April 2007
Available online 1 May 2007
Abstract—A simple and mild method for decarboxylative bromination of a,b-unsaturated carboxylic acids has been developed using
diphosphorus tetraiodide in combination with tetraethylammonium bromide (TEAB) at room temperature. High yields of the cor-
responding bromoalkenes were obtained.
ꢀ
2007 Elsevier Ltd. All rights reserved.
Decarboxylation of a,b-unsaturated carboxylic acids
accompanied by simultaneous replacement with halogen
is a useful reaction in organic chemistry for the synthesis
Diphosphorus tetraiodide is an orange crystalline solid,
and commercially available. It exhibits a high affinity for
oxygen and acts as a unique reagent able to promote
1
14
of halogenated organic substances. The original meth-
substitution of alcohols to form alkyl iodides, dehy-
1
5
od of halodecarboxylation, known as the Hunsdiecker
reaction, involves the reaction of a silver salt of the car-
boxylic acid with bromine as a halogen source. The clas-
sical reaction has been modified and developed with
dration of aldoximes to nitriles,
reactions.
and reduction
1
6
While working on decarboxylative bromination, we
observed that this reagent can be used in combination
with TEAB at room temperature for decarboxylative
bromination of a,b-unsaturated carboxylic acids. For
our initial studies, cinnamic acid was reacted with
diphosphorus tetraiodide in combination with TEAB.
A mixture of cinnamic acid (1.0 mmol), diphosphorus
tetraiodide, and TEAB (1.1 mmol) in anhydrous carbon
disulfide was stirred at room temperature. The starting
material was consumed within 9 h as indicated by
TLC analysis. After work-up and purification by silica
gel column chromatography (hexane–EtOAc, 9:1), (E)-
1-bromo-2-phenylethylene was isolated in 90% yield
2
,3
particular attention paid to green chemistry aspects,
4
operation under additive free conditions, as well as
catalysis using salt of mercury, lithium, lead, manga-
nese, or tetraalkylammonium salts. Tokuda and co-
workers reported a microwave-assisted reaction in the
5
6
7
8
9
1
0
presence of metal salts. Halodecarboxylation has also
been reported with trivalent iodine species in combina-
1
1,12
tion with N-halosuccinimide as a halogen source.
Although, most of these methods are satisfactory, the
use of more complex reagents and sometimes tedious
work-up means that there is still scope for alternative
reagent systems for decarboxylative bromination.
(
Scheme 1). The reactions were carried out in anhydrous
Iodine and iodine reagent systems have found wide-
spread application in organic synthesis because of their
selectivity and simplicity of use. Our group has been
working extensively on the development of novel meth-
odologies under mild reaction conditions using various
chloroform or acetonitrile. We also examined other halo-
gen source like tetraethylammonium chloride (TEAC)
and tetraethylammonium iodide (TEAI), to obtain the
corresponding a,b-unsaturated halides. No reaction
was observed when a combination of P I and TEAC
2
4
1
3
iodine reagents.
COOH
Br
DPTI, TEAB
Keywords: Diphosphorus tetraiodide; Tertaethylammonium bromide;
CS , r.t.
2
Decarboxylation; Bromoalkenes.
*
Corresponding author. Tel.: +91 22 24145616; fax: +91 22
4145614; e-mail: vikastelvekar@rediffmail.com
Scheme 1. Bromo-decarboxylation of cinnamic acid using DPTI and
TEAB.
2
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.137

4530
V. N. Telvekar, S. N. Chettiar / Tetrahedron Letters 48 (2007) 4529–4532
a
Table 1. Bromo-decarboxylation using DPTI and TEAB
b
c
Entry
Substrate
Product
Time (h)
9
Yield (%)
COOH
Br
1
90
93
COOH
Br
2
3
4
7
12
12
H C
H C
3
3
COOH
Br
Br
80
85
F
F
COOH
Cl
Cl
Cl
Cl
COOH
COOH
Br
5
6
7
8
9
14
12
14
8
80
85
80
88
Cl
Cl
COOH
Br
O N
O N
2
2
Br
NO2
NO2
COOH
Br
O
N
O
N
8
6
88
90
COOH
COOH
Br
Br
1
0
H CO
H CO
3
3
COOH
Br
O
O
O
O
1
1
1
1
2
3
6
8
90
85
85
COOH
Br
Br
H COCO
H COCO
3
3
COOH
10
MeOOC
MeOOC
Br
14
9
90
COOH
Br
Br
1
5
6
12
12
90
92
H C
COOH
H C
3
3
1
H C
COOH
H C
5
2
5
2
COOH
1
7
8
8
8
85
85
Br
Br
CH3
C H
CH3
COOH
1
C H
5
2
5
2
COOH
Br
1
9
0
12
12
90
86
H C
H C
5
2
5
2
COOH
Br
2
H C
H C
3
3
CH3
CH3
21
12
88
COOH
Br
H C
H C
3
3

V. N. Telvekar, S. N. Chettiar / Tetrahedron Letters 48 (2007) 4529–4532
4531
Table 1 (continued)
b
c
Entry
Substrate
Product
—
Time (h)
15
Yield (%)
COOH
COOH
d
2
2
3
NR
d
H C
2
3
—
15
NR
a
b
c
2
The reaction conditions: substrate (1.0 equiv), diphosphorous tetraiodide (1.1 equiv), TEAB (1.1 equiv), anhyd CS , rt.
Starting compounds were prepared by standard literature procedures.
1
Isolated yields after column chromatography. Structures confirmed by comparison of the IR and H NMR spectra with those of authentic
materials.
No reaction.
d
was used. The combination of P I and TEAI resulted in
occurred, while in case of (E)-a,b-unsaturated carbox-
2
4
the isolation of an unidentified complex compound.
ylic acids there was retention of configuration (Table
1, entries 1–13, 20, 21).
Encouraged by these results, a variety of a,b-unsatu-
rated aromatic and aliphatic carboxylic acids were sub-
In summary, a novel method has been developed for
decarboxylative bromination using diphosphorus
tetraiodide in combination with TEAB in anhydrous
carbon disulfide at room temperature. The method
developed is mild and gave good to excellent yields of
bromoalkenes for both aliphatic as well as aromatic
substrates.
1
7
jected to the reaction conditions, and the results are
presented in Table 1 clearly indicating that in the
absence of double bond reaction does not take place
(
Table 1, entries 21, 22). a,b-Unsaturated carboxylic
acids substituted with electron donating groups like
methyl, undergo oxidative bromo-decarboxylation
(
Table 1, entry 2) in a short reaction time and in good
yields. On the other hand, if the aromatic ring is substi-
tuted with an electron-withdrawing group such as
fluoro, nitro, or chloro, comparatively lower yields
and slower reaction rates were observed (Table 1, entries
Acknowledgment
V.N.T. thanks UGC, India for financial support under
the scheme of UGC major research project.
3
–7).
With the same reagent system, heterocyclic a,b-unsatu-
rated carboxylic acids such as 3-(2-furyl)acrylic acid also
gave good yields of the corresponding brominated prod-
ucts (Table 1, entries 8, 9). A lower reaction rate was ob-
served with aliphatic a,b-unsaturated acids: crotonic
acid (Table 1, entry 20) and 3,3-dimethylacrylic acid
References and notes
1
2
. Hunsdiecker, C. H. Ber. Disch. Chem. Ges. B 1942, 75,
91–295.
. Sinha, J.; Layek, S.; Mandal, G. C.; Bhattacharjee, M.
2
(
Table 1, entry 21).
Chem. Commun. 2001, 1916–1917.
A wide range of functional groups were tolerated by this
protocol, and under these reaction conditions, methoxy,
acetoxy, and ester groups were stable (Table 1, entries
3. Roy, S. C.; Guin, C.; Maiti, G. Tetrahedron Lett. 2001, 42,
9253–9256, and references cited therein.
4. Homsi, F.; Rousseau, G. J. Org. Chem. 1999, 64, 81–85.
5. Cristol, S. J.; Firth, W. C., Jr. J. Org. Chem. 1961, 26, 280.
6. Naskar, D.; Roy, S. J.Chem. Soc., Perkin Trans. 1 1999,
1
0–13).
1
7, 2435–2436.
. Sheldon, R. A.; Kochi, J. K. Org. React. 1972, 19, 275–
78.
. Chowdhary, S.; Roy, S. Tetrahedron Lett. 1996, 37, 2623–
624.
To study the effect of the reaction system on isomers,
Z)-phenyl-2-propenoic acid was examined. After
work-up, the crude product was isolated and subjected
to NMR analysis: no (Z)-1-bromo-2-phenylethylene
was observed. After column chromatography, pure
7
8
(
2
2
9. Naskar, D.; Roy, S. Tetrahedron 2000, 56, 1369–1377.
10. Kuang, C.; Senboku, H.; Tokuda, M. Synlett 2000, 1439–
1442.
(
E)-1-bromo-2-phenylethylene was isolated (Table 1,
entry 14). Similarly (Z)-2-butenoic acid and (Z)-2-pent-
enoic acid were converted into (E)-1-bromo-1-propene
and (E)-1-bromo-1-butene, respectively (Table 1, entries
1
1
1
1
1. Das, J. P.; Roy, S. J. Org. Chem. 2002, 67, 7861–7864, and
references cited therein.
2. Graven, A.; Jorgensen, K. A.; Dahi, S.; Stanczak, A. J.
Org. Chem. 1994, 59, 3543–3546.
1
5, 16). Further, a mixture of (E/Z)-3-phenyl-2-butenoic
acid, (E/Z)-3-phenyl-2-pentenoic acid, and (E/Z)-2-
pentenoic acid were converted into (E)-1-bromo-2-phen-
yl-1-propene, (E)-1-bromo-2-phenyl-1-butene, and
3. Telvekar, V. N.; Arote, N. D.; Herlekar, O. P. Synlett
2
005, 2495–2497.
4. Lauwers, M.; Regnier, B.; Van Eenoo, M.; Denis, J. N.;
(
E)-1-bromo-1-butene respectively (Table 1, entries 17,
8, 19). Thus it is concluded that in case of (Z)-a,b-
unsaturated carboxylic acids, inversion of configuration
Krief, A. Tetrahedon Lett. 1979, 1801–1804.
15. Suzuki, H.; Fuchita, T.; Iwasa, A.; Mishina, T. Synthesis
1978, 905–907.
1

4532
V. N. Telvekar, S. N. Chettiar / Tetrahedron Letters 48 (2007) 4529–4532
1
1
6. Newkome, G. R.; Sauer, J. D.; Erbland, M. L. Chem.
Commun. 1975, 885–886.
7. General experimental procedure: To a stirred suspension of
completely consumed (TLC). The reaction mixture was
diluted with CS and washed successively with 10% aq
sodium bisulfite solution (2 · 15 mL), 10% aq NaHCO
2
3
TEAB (1.1 equiv) in anhyd CS
2
(15 mL) was added a,b-
(2 · 15 mL), H
dried over Na
2
O (1 · 10 mL). The organic layer was
SO and concentrated in vacuo. The
unsaturated carboxylic acid (1.0 equiv). The resultant
mixture was stirred rt for 2 min followed by addition of
diphosphorus tetraiodide (1.1 equiv) and stirring was
continued at rt until the starting material had been
2
4
residue obtained was purified by silica-gel column chro-
matography (10% EtOAc–hexane) to afford pure
bromoalkenes.