Tetrahedron Letters
A novel method for bromodecarboxylation of
a,b-unsaturated carboxylic
acids using catalytic sodium nitrite
⇑
Vikas N. Telvekar , Balaram S. Takale
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A first novel synthetic utility of catalytic sodium nitrite in combination with aqueous HBr, for bromo
Received 30 December 2010
Revised 22 February 2011
Accepted 23 February 2011
Available online 12 March 2011
decarboxylation of
a,b-unsaturated carboxylic acid is described. a,b-Unsaturated carboxylic acid com-
pounds successfully converted into corresponding bromo compounds. The advantages of this protocol
are shorter reaction time and moderate to good yields.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Sodium nitrite
a,b-Unsaturated carboxylic acids
Oxidation
Bromodecarboxylation
Decarboxylation of
a
,b-unsaturated carboxylic acids accompa-
ditions but in the presence of oxygen rate of reaction increases
with the increase in the yield (Scheme 1). It was also observed that
under inert atmospheric conditions (nitrogen atmosphere), no
reaction was observed. Further no (Z) isomer was isolated from
the reaction mixture. To study the effect of the reaction system
on (Z) isomers, (Z)-phenyl-2-propenoic acid was subjected under
this reaction condition. After work-up, the crude product was
isolated and subjected to NMR analysis: no (Z)-1-bromo-2-phenyl-
ethylene was observed. After column chromatography, only pure
(E)-1-bromo-2-phenylethylene was isolated.
nied by simultaneous replacement with halogen is a useful reac-
tion in organic chemistry for the synthesis of halogenated
organic substances.1 There are several methods reported for the
decarboxylative bromination by using salt of mercury, lithium,
lead and manganese.2 Halodecarboxylation has also been reported
with trivalent iodine species in combination with N-halosuccini-
mide as a halogen source.3 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.
Further screening of the reaction conditions revealed that
0.05 equiv of NaNO2 is sufficient to carry out reaction. We also
examined other halogen source like HCl and HI, to obtain the cor-
Our group has been working extensively on the development of
novel methodologies under mild conditions. After successfully
studying the use of hypervalent iodine reagent,4 in bromodecarb-
responding
a,b-unsaturated halides. No reaction was observed
oxylation of
a
,b-unsaturated carboxylic acids our next goal was to
when a combination of NaNO2 and HCl was used, while the combi-
nation of NaNO2 and HI resulted in the isolation of an unidentified
compound. No reactions were observed when 48% HBr was
replaced by tetraethylammonium bromide and N-bromo-succina-
mide as bromine sources.
develop a catalytic process with easily available shelf reagents for
bromodecarboxylation. We observed that in the presence of
catalytic amount of NaNO2 and oxygen with 48% aqueous HBr the
reaction yielded
a,b-unsaturated bromide, providing an interesting
route to ,b-unsaturated bromide. NaNO2 is an easily available shelf
a
Br
reagent and recently used for bromination and iodination of
catalytic NaNO2, 48% aq.HBr, O2
aromatic and alkene compounds.5
acetonitirle, 5 hr, rt
90% yield
COOH
Reaction of NaNO2 (1.1 equiv) with cinnamic acid (1.0 equiv) in
the presence of 48% HBr (2 equiv) in acetonitrile at room temper-
ature for long reaction time resulted in the formation of poor yield
of corresponding (E)-a,b-unsaturated bromo compound by decarb-
oxylative reaction. It was observed that under similar reaction con-
Br
catalytic NaNO2, 48% aq.HBr
acetonitirle, 48 hr, rt
5% yield
⇑
Corresponding author. Tel.: +91 22 24145616; fax: +91 22 24145614.
Scheme 1. Formation of a,b-unsaturated bromide using NaNO2.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.