Ultrasonically Assisted Decarboxylative Bromination of α,β-Unsaturated Carboxylic Acids under Vilsmeier-Haack Conditions

Article abstract of DOI:10.1080/15533174.2014.989573

An efficient method for decarboxylative bromination of cinnamic acids (α,β-unsaturated carboxylic acids or 3-arylpropenoic acids) was achieved under relatively mild conditions using Vilsmeier-Haack reagent and KBr in acetonitrile media. Vilsmeier-Haack reagent is prepared by using 1:1 ratio of oxychloride (SOCl₂ or POCl₃) and DMF under chilled condition. Ultrasonically assisted reactions underwent smoothly with highly significant rate enhancements and afforded bromostyrenes as products in very good yields even though the reactions were too sluggish.

Full text of DOI:10.1080/15533174.2014.989573

Synthesis and Reactivity in Inorganic, Metal-Organic, and
Nano-Metal Chemistry
ISSN: 1553-3174 (Print) 1553-3182 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt20
Ultrasonically Assisted Decarboxylative
Bromination of α,β-Unsaturated Carboxylic Acids
Under Vilsmeier-Haack Conditions
M. Satish Kumar, K. C. Rajanna, P. Venkanna, M. Venkateswarlu & V.
Sudhakar Chary
To cite this article: M. Satish Kumar, K. C. Rajanna, P. Venkanna, M. Venkateswarlu & V.
Sudhakar Chary (2016) Ultrasonically Assisted Decarboxylative Bromination of α,β-Unsaturated
Carboxylic Acids Under Vilsmeier-Haack Conditions, Synthesis and Reactivity in Inorganic,
Metal-Organic, and Nano-Metal Chemistry, 46:5, 642-646, DOI: 10.1080/15533174.2014.989573
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry (2016) 46, 642–646
Copyright © Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2014.989573
Ultrasonically Assisted Decarboxylative Bromination
of a,b-Unsaturated Carboxylic Acids Under
Vilsmeier-Haack Conditions
M. SATISH KUMAR, K. C. RAJANNA, P. VENKANNA, M. VENKATESWARLU, and V. SUDHAKAR CHARY
Department of Chemistry, Osmania University, Hyderabad, A. P., India
Received 26 October 2013; accepted 3 November 2014
An efficient method for decarboxylative bromination of cinnamic acids (a,b-unsaturated carboxylic acids or 3-arylpropenoic acids)
was achieved under relatively mild conditions using Vilsmeier-Haack reagent and KBr in acetonitrile media. Vilsmeier-Haack
reagent is prepared by using 1:1 ratio of oxychloride (SOCl2 or POCl3) and DMF under chilled condition. Ultrasonically assisted
reactions underwent smoothly with highly significant rate enhancements and afforded bromostyrenes as products in very good yields
even though the reactions were too sluggish.
Keywords: sonication, rate enhancements, decarboxylative bromination, a,b-unsaturated acids, Vilsmeier-Haack reagent,
bromostyrenes
Introduction
Even though, the findings of Hunsdiecker made a mark in
organic synthesis for the conversion of a,b-unsaturated carbox-
Bromination is a fundamental and very useful reaction in organic ylic acids to corresponding b–bromostyrenes, the reaction suf-
synthesis due to the commercial importance of bromo organics fered with low product yields and the use of toxic and hazardous
that are used in the synthesis of various natural products, as well materials such as CCl4 and molecular bromine. This prompted
as in the manufacture of pharmaceuticals, and intermediates for several groups of workers to modify and improve the greenery of
agrochemicals. Bromoaromatics such as b-bromostyrenes are this reaction. Several reagents, catalysts, and conditions were
used as food additives and fragrance in consumer products. It is tried to make it eco-friendly.[6–12] During the past few years we
used as a perfume that is most commonly added to soaps. The have concentrated our efforts to develop greenery methods[13–16]
administration of b-bromostyrene to the rat results in a fall in the for nitro decarboxylation,[14a] nitration,[14b] bromination,[15] and
level of hepatic glutathione.[1] Bromo derivatives are used in the sulfonation[16] of aromatic compounds under nonconventional
preparation of organometallic reagents,[2] used as potential anti- conditions. In recent past, enormous interest has been paid for
tumor, antibacterial, antifungal, antineoplastic, antiviral, and the development of environmentally safe and economically via-
antioxidizing agents[3] and play a vital role in transition metal– ble methods in organic synthesis in the lines of Green Chemis-
mediated coupling reaction.[4] Halodecarboxylation of metal try.[17] One such effort is the drive for the development of
carboxylate with molecular halogen is generally known as Huns- ultrasonically assisted or sonicated reactions using ultrasound to
diecker reaction.[5] In the basic investigations, Ag(I) salts of car- trigger/accelerate the progress of reactions. Earlier reviews and
boxylic acids reacted with halogens to give unstable publications[18–20] in this field proved the importance of ultrason-
intermediates which readily decarboxylate thermally to yield ically assisted organic synthesis and also highlighted that this
alkyl halides. The reaction is believed to involve homolytic cleav- technique is not only simple, but also satisfies both economical
age of the C-C bond and a radical chain mechanism.
and environmental demands. In the present work we have suc-
cessfully developed a synthetic protocol for the synthesis of
Address correspondence to K. C. Rajanna, Department of
Chemistry, Osmania University, Hyderabad-500 007, A. P.
India. E-mail: kcrajannaou@yahoo.com
Sch. 1. Decarboxylative bromination of unsaturated acids.

Decarboxylative Bromination of Unsaturated Acids
643
Table 1. Decarboxylative bromination of cinnamic acids using Vilsmeier-Haack reagent in acetonitrile media at room temp (isolated
yields)
SOCl2/DMF
POCl3/DMF
S. N
a,b USA (C A)
Product
b-Bromostyrene
4-Cl b-Bromostyrene
4-OMe b-Bromostyrene
4-Me b-Bromostyrene
4-NO2 b-Bromostyrene
4-OH b-Bromostyrene
1-Bromo ethene
Conventional
Sonication
Conventional
Sonication
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CA
68
65
64
62
54
70
55
58
62
52
55
60
65
58
58
52
72
68
68
65
58
74
58
62
65
55
60
62
70
62
60
56
68
66
65
65
58
70
58
60
64
54
60
62
68
60
60
55
75
70
70
70
64
75
60
65
68
58
65
65
72
65
65
60
4-Cl CA
4-OMe CA
4-Me CA
4-NO2 CA
4-OH CA
AA
CRA
3-Phenyl CRA
2-Me CA
2-Cl CA
4-Br CA
1-Bromopropene
1-Bromo-3-phenyl propene
2-Me b-Bromostyrene
2-Cl b-Bromostyrene
4-Br b-Bromostyrene
4-F b-Bromostyrene
1-Br-2-Furyl ethene
4-F C A
3-Furyl-1-propenoic acid
2-OMe C A
3-Napthyl-1-acrylic acid
2-OMe b-Bromostyrene
2-(b-Bromovinyl) naphthalene
Reaction times: Conventional method-7–8 hrs; Sonication-45-60min USA D Unsaturated carboxylic acid; CA D Cinnamic acid; AA D Acrylic acid; CRA D
Crotonic acid.
Sch. 2. Mechanism with DMF/oxychloride in presence of KBr.

644
Satish Kumar et al.
Table 2. Spectroscopic data of b-bromostyrenes
S. N
Product
Spectral data
1
2
3
4
5
6
7
8
b-Bromostyrene
1H NMR (CDCl3)d6.75 (d, 1H, J D 14Hz), 7.14 (d,1H, J D 14Hz), 7.26–7.36 (m, 5H,Ar-H); m/
z D 182; (Colorless oil)
4-Cl b-Bromostyrene
4-Br b-Bromostyrene
4-F b-Bromostyrene
4-OMe b-Bromostyrene
4-Me b-Bromostyrene
4-NO2 b-Bromostyrene
4-OH b-Bromostyrene
1H NMR (CDCl3) d6.75 (d, 1H, J D 14Hz), 7.02 (d,1H, J D 14Hz), 7.22 (d, 2H,Ar-H, J D
8.5Hz), 7.34(d, 2H, Ar-H, J D 8.5Hz); m/z D 216; mp D 47–50ꢀC
1H NMR (CDCl3)d6.76 (d, 1H, J D 14.25Hz), 7.06 (d, 1H, J D 14.25Hz), 7.18(d, 2H, Ar-H, J D
8.5Hz), 7.42 (d, 2H, Ar-H, J D 8.5Hz); m/z D 260; mp D 67–70ꢀC
1H NMR (CDCl3) d6.65 (d, 1H, J D 13.5Hz), 6.96 (d, 2H, Ar-H, J D 9.25Hz), 7.05 (d, 1H, J D
13.5Hz), 7.21–7.26 (d, 2H, Ar-H, 9.25Hz); m/z D 200 (Colorless oil)
1H NMR (CDCl3) d 3.76(s, 3H), 6.58 (d, 1H, J D 14Hz), 6.82 (d, 2H, Ar-H, J D 9Hz), 7.02 (d,
1H, J D 14Hz) 7.24 (d, 2H, Ar-H, J D 9Hz); m/z D 212; mp D 59–63ꢀC
1H NMR (CDCl3) d 2.35 (s, 3H),6.72 (d, 1H, J D 13.75Hz), 7.12 (d, 1H, J D 13.75Hz), 7.16(d,
2H, Ar-H, J D 8.25Hz), 7.25 (d, 2H, Ar-H, J D 8.25Hz); m/z D 196; mp D 47–51ꢀC
1H NMR (CDCl3) d 6..74 (d, 1H, J D 14.5Hz) 7.16 (d, 1H, J D 14.5Hz), 7.75 (d, 2H, Ar-H, J D
9.25Hz), 8.24 (d, 2H, Ar-H, J D 9.25HZ); m/z D 227; mp D 158–162ꢀC
1H NMR (CDCl3) 5.26(s, 1H, Ar-OH). d6.72(d, 1H, J D 14.75Hz), 6.95(d, 1H, J D 14.75Hz),
7.02–7.10 (d, 2H, Ar-H, J D 9Hz), 7.28–7.45 (d, 2H, Ar-H, J D 9Hz); m/z D 198; mp D 186–
191ꢀC
9
1-Bromopropene
1H NMR (CDCl3) d 1.72 (d, 3H, J D 5.75Hz), 5.86 (d, 1H, J D 14.25Hz), 6.02–6.16(m, 1H),; m/
z D 120; (yellow color oil)
10 1-Bromo-3-phenyl propene
11 1-Bromo-2-Furyl ethene
12 1-Bromoethene
1H NMR (CDCl3) d 2.96 (d, 2H, J D 14Hz), 5.92(d, 1H, J D 14Hz), 6.68 (m, 1H), 7.02–7.12(m,
5H); m/z D 196 (yellow color oil)
1H NMR (CDCl3) d 6.68 (d, 1H, J D 13.5Hz), 7.12 (d, 1H, J D 8Hz), 7.38—7.65 (m, 3H, Ar-H);
m/z D 172; (pale yellow color oil)
1H NMR (CDCl3) d5.80 (dd, 1H, J D 9.5Hz, J D 1.25Hz); 6.55 (dd, 1H, J D 13.75Hz, J D
9.5Hz); 7.12(dd, 1H, J D 13.25Hz, J D 1.25Hz); m/z D 106; (Colorless oil)
1H NMR (CDCl3) d 2.24 (s, 3H,-Me), 6.94(d, 1H, J D 13.75Hz), 7.15–7.64 (m, 4H, Ar-H), 8.12
(d, 1H, J D 13.75Hz); m/z D 196 (pale yellow color oil)
13 2-Me b-Bromostyrene
14 2-Cl b-Bromostyrene
15 2-OMe b-Bromostyrene
1H NMR (CDCl3) d6.82 (d, 1H, J D 13.85Hz), 7.22–7.58 (m, 4H, Ar-H), 7.85 (d, 1H, J D
13.85Hz); m/z D 216 (Colorless oil)
1H NMR (CDCl3):d3.88 (s, 3H,-OMe), 6.82 (d, 1H, J D 14Hz), 6.94 (d, 1H, J D 14Hz), 7.24–
7.36 (m, 4H, Ar-H); m/z D 212 (pale yellow color oil)
16 2-(b-Bromovinyl) naphthalene) 1H NMR (CDCl3) d6.95 (d, 1H, J D 13.85Hz), 7.22 (d, 1H, J D 13.85Hz), 7.44–7.49 (m, 3H, Ar-
H), 7.69–7.84 (m, 4H, Ar-H); m/z D 232; mp D 84–88 OC
b-bromostyrenes through decarboxylative bromination of recorded on Bruker UXNMR/XWIN-NMR Avance-
a,b-unsaturated acids using Vilsmeier-Haack reagent and labo- 300 MHz, and GEMINI spectrometers. Chemical shifts are
1
ratory desk top chemical KBr under conventional and ultrasonic reported downfield from TMS (d D 0) for H NMR. EI-MS
conditions.
spectra were recorded on a Shimadzu GC-MS instrument
(GCMS-QP2010 plus).
Experimental
Synthesis of b-Bromostyrenes Using Vilsmeier-Haack
Reagent Under Conventional Conditions
All chemicals were of reagent grade and were obtained from
Aldrich, Lancaster, Fluka, or local companies. The Vilsme-
ier-Haack reagent is prepared afresh before use from oxy- 0.01 mol of organic substrate (cinnamic acids), 0.015 mol of
chloride (POCl3or SOCl2) and DMF. To a chilled (at ¡50ꢀC) Vilsmeier-Haack reagent, and KBr and acetonitrile solvent
oxychloride in acetonitrile solvent, a calculated amount of (Me CN) were taken in a previously cleaned in a round-bot-
dimethylformamide was slowly added dropwise, which tom flask and stirred for about 7–8 h at room temperature.
resulted in a slurry indicating the formation of Vilsmeier- After completion of the reaction, as confirmed by TLC, the
Haack reagent or iminium salt.
reaction mixture is treated with sodium thiosulfate solution,
Melting points were recorded on an electrothermal melting followed by the addition of ethyl acetate. The organic layer
point apparatus and are uncorrected. NMR spectra were was separated, dried over Na2SO4 and evaporated under

Decarboxylative Bromination of Unsaturated Acids
645
vacuum, purified with column chromatography using pet of a,b-unsaturated carboxylic acids under Vilsmeier-Haack
ether: ethyl acetate as eluent to get pure product.
conditions. The reactions afforded b-bromostyrenes as prod-
ucts in moderate to good yields. The present protocol is a
clean reaction method with a simple workup.
Ultrasonically Assisted Vilsmeier-Haack Synthesis of
b-Bromostyrenes (Sonication)
Acknowledgments
To a centimolar cinnamic acid, 0.015 mol of Vilsmeier-Haack
reagent and KBr and solvent (Me CN) were added in a clean
in a round bottom flask and clamped in a sonicator at room
temperature. After completion of the reaction, as ascertained
by TLC, the reaction mixture is treated with sodium thiosul-
fate solution, followed by the addition of ethyl acetate. The
separation and purification procedure is by and large similar
to the above procedure.
The authors are indebted to Prof. T. Navaneeth Rao (Former
Vice-Chancellor, O.U) and Prof. P. K. Saiprakash (Former
Dean, Faculty of Science, O.U), Principal, Nizam College
and Head, Department of Chemistry, O.U) for constant
encouragement and facilities.
Funding
Results and Discussion
The authors would sincerely thank CSIR and UGC, New
Delhi for financial support in the form JRF to V. Sudhakar
chary and Rajiv Gandhi Post Doctoral Fellowship to Dr. M.
Venkateswarlu.
A perusal of literature shows that N,N-dimethylformamide
(DMF) and oxychlorides such as phosphorus oxychloride
(POCl3) or thionyl chloride (SOCl2) are generally used for the
preparation of halomethyleniminium (Vilsmeier-Haack
reagent), which in turn is used for effective formylation of a
large number of heterocyclic compounds. Even though Vilsme-
ier-Haack reaction is a mild method, it could be used to trigger
bromination, nitration and sulfonation reactions.[13–16]
Encouraged by these results, we have tried to examine this pro-
tocol for decarboxylative bromination reactions for the synthe-
sis of b-bromostyrenes from a,b-unsaturated acids.
Vilsmeier-Haack reagent reactions with a,b-unsaturated
acids underwent decarboxylative bromination in presence of
KBr and afforded b-bromostyrenes in (Scheme 1) in good
yields (Table 1) at room temperature with constant stirring
for 7–8 h. Mechanism of the reaction could be explained
through the formation of halomethyleniminium slat in the
first step, which in turn reacts with cinnamic acid and KBr
and generates a bromoniumcinnamate intermediate (cyclic
bromonium ion intermediate) as shown in Scheme 2. Bromo-
niumcinnamate thus formed rearranges to afford b-Bromos-
tyrenes followed by decarboxylation. Formation of such
cyclic bromonium ion intermediate could be supported from
earlier literature reports.[9,10] The products were characterized
by spectroscopic methods, as shown in Table 2.
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