November 2009
Chem. Pharm. Bull. 57(11) 1243—1245 (2009)
1243
a b
Novel System for Decarboxylative Bromination of , -Unsaturated
Carboxylic Acids with Diacetoxyiodobenzene
Ravindra Abhykumar FURSULE, Pravin Onkar PATIL,* Bharti Devaji SHEWALE,
Satish Bhaskar KOSALGE, Prashant Krishnarao DESHMUKH, and Dilip Ashok PATIL
Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research; Shirpur
425405, Maharashtra, India. Received May 21, 2009; accepted August 7, 2009; published online August 17, 2009
A simple and mild method for the conversion of varieties of a,b-unsaturated carboxylic acids to the corre-
sponding bromoalkenes using diacetoxyiodobenzene (IBD) in combination with tetraethyl-ammonium bromide
(TEAB) at room temperature is discussed. Advantages of this system are short reaction time, easy work up and
gave good to excellent yields.
Key words diacetoxyiodobenzene; a,b-unsaturated carboxylic acid; tetraethyl-ammonium bromide; bromoalkene
Halodecarboxylation of the corresponding carboxylic acid (IBD) in combination with TEAB at room temperature.
is widely used to obtain bromides. Decarboxylation of a,b- Starting compounds viz. a,b-unsaturated carboxylic acids
unsaturated carboxylic acids accompanied by simultaneous were prepared by standard literature procedures.16—21) For our
replacement with halogen is a useful reaction in organic initial studies, cinnamic acid was selected as model substrate
chemistry for synthesis of halogenated organic substances. and the reaction was carried out with IBD in combination
However, this reaction requires a heavy metal salt and high with TEAB. A mixture of cinnamic acid (1.0 mmol), IBD (1.1
reaction temperature, which restricts its application.1) Be- mmol) and TEAB (1.1 mmol) in anhydrous dichloromethane
sides, the classical Hunsdiecker reaction which is very ineffi- was stirred at room temperature. It was observed that the
cient for cinnamic acid analogs, for example, the bromode- starting material was consumed within 15—20 min as indi-
carboxylation of cinnamic acids under classical conditions cated by TLC analysis. After work-up and purification by
gives the desired product in less than 15% yield.2) It is there- silica gel column chromatography (hexane–ethyl acetate
fore infeasible to synthesize vinyl bromide via this approach. (EtOAc), 9 : 1), b-bromostyrene was isolated in 95% yield
Thereafter, several attempts to improve the Hunsdiecker re- (Chart 1).
action to convert cinnamic acids to corresponding bromide
were made with various reagents and conditions. However, Results and Discussion
salt or certain equipments such as microwave reactor is still
Encouraged by this result, we subjected various cinnamic
needed.3) The classical Hunsdiecker reaction has been modi- acid analogs, including halogenated, aminated, nitrated,
fied and developed with particular attention paid to green methoxylated and aliphatic a,b-unsaturated carboxylic acids,
chemistry aspects.4,5) Tokuda et al. reported a microwave- to the reaction conditions established above; the results are
assisted reaction in the presence of metal salts.6) Halodecar- summarized in Table 1.
boxylation also reported with trivalent iodine species in com-
It clearly indicates that in the absence of double bond reac-
tion does not take place (Table 1, entries 12, 14, 16). a,b-
bination with N-halosuccinimide as a halogen source.7,8)
Hypervalent iodine compounds are extensively used for a Unsaturated carboxylic acids substituted with electron donat-
variety of chemical transformations and particularly as ox- ing groups like methyl, undergo oxidative bromo-decarboxy-
idative reagents because of their selectivity and simplicity of lation (Table 1, entry 7) in a short reaction time and in good
use. Ever since the innovative work by Telvekar et al.9) Ex- yields. On the other hand, if the aromatic ring is substituted
plorations into the chemistry of hypervalent iodine com- with an electron-withdrawing group such as fluoro, nitro, or
pounds became the subject of growing interest due to their chloro, comparatively lower yields and slower reaction rates
mild nature.10—12) Although there are practical approaches for were observed (Table 1, entries 3—6, 8). Using the same
converting cinnamic acids to b-bromostyrene, the methods reagent system, 3-(2-furyl) acrylic acid also gave good yields
developed to date have drawbacks viz. requirement for multi- of the corresponding brominated products (Table 1, entry 11).
ple steps, complex or dangerous reagents like diphosphorus Aliphatic a,b-unsaturated acids such as crotonic acid etc.
tetraiodide13) and tedious work-up procedures. Thus, a con- give lower yields of brominated products (Table 1, entries 13,
venient halodecarboxylation method is still needed. Diace- 15).
toxyiodobenzene in combination with tetraethyl-ammonium
bromide (TEAB) has been utilized in several transformations
like synthesis of (ꢀ)-dibromophakellstatin14) and oxidation
of alcohols.15) Tetra ethyl ammonium bromide has advantage
of its byproduct being water soluble and easy work up proce-
dure over other brominating agent such as N-bromosuccin-
imide whose byproduct is soluble in organic solvent.
Herein, we report our preliminary results on decarboxyla-
tive bromination of a,b-unsaturated carboxylic acids to the
Chart 1. Bromo-Decarboxylation of Cinnamic Acid Using IBD and
corresponding bromoalkenes using diacetoxyiodobenzene TEAB
© 2009 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: rxpatilpravin@yahoo.co.in