α-bromination of 1,3-dicarbonyl compounds using Dess-Martin periodinane (DMP) and tetraethylammonium bromide (TEAB)

Article abstract of DOI:10.1080/00397910601033641

A mild and expeditious method for α-bromination of 1,3-dicarbonyl compounds using Dess-Martin periodinane and tetraethylammonium bromide is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601033641

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α‐Bromination of 1,3‐Dicarbonyl Compounds
Using Dess–Martin Periodinane (DMP) and
Tetraethylammonium Bromide (TEAB)
Paresh D. Salgaonkar a , Vidyanand G. Shukla a & Krishnacharya G.
Akamanchi a
a Department of Pharmaceutical Sciences and Technology, University
Institute of Chemical Technology, Matunga, Mumbai, India
Published online: 25 Jul 2007.
To cite this article: Paresh D. Salgaonkar , Vidyanand G. Shukla & Krishnacharya G. Akamanchi (2007)
α‐Bromination of 1,3‐Dicarbonyl Compounds Using Dess–Martin Periodinane (DMP) and Tetraethylammonium
Bromide (TEAB), Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 37:2, 275-280, DOI: 10.1080/00397910601033641
To link to this article: http://dx.doi.org/10.1080/00397910601033641
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Synthetic Communicationsw, 37: 275–280, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601033641
a-Bromination of 1,3-Dicarbonyl
Compounds Using Dess–Martin
Periodinane (DMP) and
Tetraethylammonium Bromide (TEAB)
Paresh D. Salgaonkar, Vidyanand G. Shukla, and
Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology, University
Institute of Chemical Technology, Matunga, Mumbai, India
Abstract: A mild and expeditious method for a-bromination of 1,3-dicarbonyl
compounds using Dess–Martin periodinane and tetraethylammonium bromide is
described.
Keywords: bromination, Dess–Martin periodinane, 1,3-dicarbonyl compounds, tetra-
ethylammonium bromide
INTRODUCTION
a-Brominated 1,3-dicarbonyl compounds are versatile intermediates in organic
synthesis. Hence a-bromination of 1,3-dicarbonyl compounds is one of the
important transformations in synthetic organic chemistry.[1] Classical reagents
for a-bromination of 1,3-dicarbonyl compounds include the use of bromine,
.
N-bromosuccinimide (NBS), 4-dimethylaminopyridine (DMAP) HBr3, and
CuBr2/KBr.[2] However, these reagents suffer with the disadvantages of
highly acidic conditions, unwanted oxidations, side reactions involving free
radicals, and/or long reaction times. Coats and Wassermann[3] demonstrated
the use of Koser’s reagent, [hydroxy(tosyloxy)iodo] benzene, in the presence
Received in the USA June 5, 2006
Address correspondence to K. G. Akamanchi, Department of Pharmaceutical
Sciences and Technology, University Institute of Chemical Technology, Matunga,
Mumbai 400 019, India. E-mail: kgap@rediffmail.com
275

276
P. D. Salgaonkar, V. G. Shukla, and K. G. Akamanchi
of a slight excess of CuBr2 in acetonitrile at 08C, for selective preparation of
a-bromo-1,3-diones in high yields. a-Halogenation of carbonyl compounds
with the use of Koser’s reagent and magnesium halides under microwave
conditions is also documented in the literature.[4]
Yang et al.[5] reported on the use of N-bromosuccinimide in combination
with Lewis acid, Mg(ClO4)2, to afford mild and fast a-bromination of a wide
range of functionalized 1,3-dicarbonyl compounds.
Pentavalent iodine reagents have found widespread applications in
organic synthesis because of their selectivity and simplicity in use. Because
we are interested in the reactivity and selectivity of these reagents, our
group is working extensively to use these reagents to perform selective
transformations under mild conditions.[6] In this communication, we report
our results on the bromination of 1,3-dicarbonyl compounds with Dess–
Martin periodinane (DMP) in combination with tetraethylammonium
bromide (TEAB).
RESULTS AND DISCUSSION
In a preliminary experiment on a-bromination of 1,3-dicarbonyl compounds,
acetyl acetone was selected as a substrate to optimize the reaction conditions.
On addition of acetyl acetone to a dry chloroform solution of DMP and TEAB,
the starting material was consumed within 5 min. Workup followed by purifi-
cation by silica-gel column chromatography using EtOAc–hexane (1:9)
afforded the a-monobrominated compound 1 (R55CH3, 3-bromo-2,4-pentane-
dione) in 54% yield, a,a-dibrominated compound 2 (R55CH3, 3,3-dibromo-
2,4-pentanedione) in 28% yield, and interestingly the compound 3
(R55CH3,1-(2-bromo-1-methyl-3-oxo-1-butenyloxy)-1H-1l3-benzo[d][1,2]
iodoxol-3-one) in 18% yield (Scheme 1). [Compound 3 (R55CH3) from acetyl
1
acetone: H NMR: d 2.49 (s, 6H), 7.12–7.49 (m, 2H), 7.72–7.98 (m, 2H).
Compound C (R55OCH2CH3) from ethyl acetoacetate: 1H NMR: d 1.25
(t, J ¼ 7.20 Hz, 3H), 2.61 (s, 3H), 4.17 (q, J ¼ 7.20 Hz, 2H), 7.04 (m, 2H),
7.89 (m, 2H).] Further, in another experiment with ethyl acetoacetate, again
the formation of all the three corresponding compounds (R55OEt,
Scheme 1) was observed in the ratio of 49:29:22 respectively.
Scheme 1.

a-Bromination of 1,3-Dicarbonyl Compounds
277
To avoid the formation of compound 3, we envisaged the possibility of
adding methanol to the chloroform solution of DMP/TEAB prior to the
addition of substrate, expecting that the methanol will rapidly exchange
with the acetyl group in the iodine(III) compound, 1-(acetyloxy)-1H-1l3-
2-benzo[d][1,2]iodoxol-3-one, and undergo oxidation to form formaldehyde
and o-iodobenzoic acid. As expected, the formation of the compound 3 was
avoided by the addition of methanol, and o-iodobenzoic acid was recovered.
Ethyl/methyl acetoacetates underwent a-monobromination readily, and
starting materials disappeared within 5 min (as indicated by thin-layer chro-
matography, TLC); however, after some time, the initially formed
a-monobromo products were unstable and readily disproportionated to give
dibrominated compounds 2 (R55OCH2CH3, OCH3, Scheme 1) and ethyl/
methyl acetoacetates. 2-Methyl-1,3-cyclopentanedione gave good yields of
a-brominated product. However, in the case of 1,3-cyclohexanediones, the
results were different. The reaction of 5,5-dimethyl-1,3-cyclohexanedione
(dimedone) with the developed system gave the spiro compound
4 [40,40,6,6-tetramethyl-3,5,6,7-tetrahydro-4H-spiro[1-benzofuran-2,10-cyclo-
hexane]-20,4,60-trione], in ꢀ60% yield (Scheme 2).[7] The formation of the
spiro compound 4 was confirmed by its physical constants and spectral pro-
perties. [Spectral data for compound 4, f40,40,6,6-tetramethyl-3,5,6,7-tetra-
hydro-4H-spiro[1-benzofuran-2,10-cyclohexane]-20,4,60-trioneg (Scheme 2):
mp 207–2088C [lit.[10] mp 205–2108C]; 1H NMR (CDCl3, 60 MHz): d
0.97 (m, 12H), 2.04 (m, 10H); MS (EI): 290 (Mþ).] There is a literature
precedent for the formation of this spiro compound 4 by the reaction of
dimedone with formaldehyde in the presence of iodine.[8] In the present
case, the formation of spiro compound 4 could be due to formation of a
dimedone-formaldehyde adduct in situ by the reaction of dimedone with
the generated formaldehyde from the oxidation of added methanol and
the presence of tetraethylammonium[(di(acetyloxy)bromate(I)][6a,9] in the
reaction medium.
Scheme 2.
The reaction was performed on dimedone in the absence of methanol;
however, a mixture of products was formed. With 1,3-cyclohexanedione, a
complex mixture of products resulted.
The reaction of phenylacetone with the developed system gave the corres-
ponding a-monobrominated compound in 81% yield (Scheme 3).

278
P. D. Salgaonkar, V. G. Shukla, and K. G. Akamanchi
Scheme 3.
To explain the mechanism, we presumed that the 1,3-dicarbonyl
compound existed predominantly in its enolic form. The reactive species
generated from DMP and TEAB may be regarded as tetraethylammonium
[di(acetyloxy)bromate(I)], which reacted with the enolic double bond to
give an envisaged bromonium ion intermediate (Scheme 4).
Scheme 4.
The residue obtained on completion of a-monobromination of 1,3-dicar-
bonyl compounds was identified as o-iodobenzoic acid, which can be re-
oxidized to DMP using standard literature procedures.[10]
In summary, we have developed an expeditious method for a-monobro-
mination of 1,3-dicarbonyl compounds including b-keto esters. The method
can also be extended in the preparation of a-bromo carbonyl compounds.
EXPERIMENTAL
All the synthesized a-bromo-1,3-dicarbonyl compounds are previously
1
known compounds in the literature. All H NMR spectra were recorded on
a Jeol JNM-MY 60 FT instrument at 60 MHz. Chemical shifts are

a-Bromination of 1,3-Dicarbonyl Compounds
279
expressed in d units relative to the tetramethylsilane (TMS) signal as the
internal reference in CDCl3. Mass spectra were recorded on a Finnigan Mat
1020B, by EI (70 eV) ionization. All the solvents were purchased from com-
mercial sources and used without further purification.
Representative Experimental Procedure
To a stirred solution of TEAB (1.1 eq) in 10 ml of CHCl3, DMP (1.1 eq) was
added, followed by the addition of methanol (2.0 eq). The mixture was stirred
at room temperature for 5 min, followed by the addition of 1,3-dicarbonyl
compound (1.0 eq). The reaction mixture was stirred for an additional 5 min
until complete consumption of starting material was observed on TLC. The
reaction mixture was diluted with CH2Cl2, washed successively with 10%
sodium bisulfite solution (2 ꢀ 15 ml), saturated sodium bicarbonate solution
(2 ꢀ 15 ml), water (2 ꢀ 15 ml), and brine (1 ꢀ 15 ml). The organic layer
was dried over sodium sulfate and concentrated. On purification over silica
gel (EtOAc/hexane), the residue afforded the mono bromo derivatives.
ACKNOWLEDGMENT
The authors thank the Council of Scientific and Industrial Research (CSIR),
the University Grants Commission (UGC), New Delhi, for financial support
and UGC, New Delhi, for infrastructure under the Department of Special
Assistance (DSA) program.
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