Oxybromination of ethynylbenzene catalysed by molybdenum complexes in organic solvent and in ionic liquids

Article abstract of DOI:10.1002/adsc.200505114

The molybdenum(VI)-catalysed oxybromination of ethynylbenzene was performed with hydrogen peroxide as oxidant and potassium bromide as source of bromine, in a two-phase water/solvent system, where solvent was either dichloromethane or an ionic liquid. The selectivity was toward 1,2-dibromostyrene when performed in water/dichloromethane. In ionic liquids better yields and shorter reaction times were obtained that, together with the complete ethynylbenzene conversion and the preferred formation of α,α-dibromoacetophenone, make the reaction synthetically useful.

Full text of DOI:10.1002/adsc.200505114

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Oxybromination of Ethynylbenzene Catalysed by Molybdenum
Complexes in Organic Solvent and in Ionic Liquids
Valeria Conte, Barbara Floris,* Pierluca Galloni, Adriano Silvagni
Dipartimento di Scienze e Tecnologie Chimiche, Universit a` di Roma “Tor Vergata”, Via della Ricerca Scientifica,
I-00133 Roma, Italy
Fax: (þ39)-06-7259-4328, e-mail: floris@uniroma2.it
Received: March 17, 2005; Accepted: May 16, 2005
Abstract: The molybdenum(VI)-catalysed oxybromi-
nation of ethynylbenzene was performed with hydro-
gen peroxide as oxidant and potassium bromide as
source of bromine, in a two-phase water/solvent sys-
tem, where solvent was either dichloromethane or an
ionic liquid. The selectivity was toward 1,2-dibro-
mostyrene when performed in water/dichlorome-
thane. In ionic liquids better yields and shorter reac-
Scheme 1. Mo(VI)-catalysed oxybromination of ethynylben-
tion times were obtained that, together with the
zene with hydrogen peroxide and KBr in water/halogenated
complete ethynylbenzene conversion and the prefer-
solvent.
red formation of a,a-dibromoacetophenone, make
the reaction synthetically useful.
Subsequently, reactivity and selectivity were improved
Keywords: alkynes; green chemistry; ionic liquids;
molybdenum(VI); oxybromination
by using environmental benign ionic liquids (ILs), in-
stead of the molecular solvent.
[
5]
In view of these results, it seemed desirable to investi-
gate whether the oxybromination reaction in these sys-
tems could be extended to alkynes. We report here the
Alkynes have accompanied organic chemistry from the results obtained on reacting ethynylbenzene with
very beginning and are still an important class, because H O /KBr. Since bromination of this alkyne is expected
2
2
[
6]
they can be used as building blocks for complex mole- to be more difficult than that of styrene, the more reac-
cules or transformed into different functional groups, tive Mo(VI) species was used as catalyst.
taking advantage of similarities and differences with The oxybromination reaction of ethynylbenzene was
[
7]
[
1]
the reactivity of alkenes. Among the alkene reactions, carried out at room temperature in a two-phase system
the oxybromination by vanadium(V) complexes could H O/CH Cl . The reaction output (Scheme 1) was quan-
2
2
2
be performed with cheap and non-toxic reagents, such tified by GC analyses, with dodecane as internal stand-
[
2–4]
as hydrogen peroxide and KBr.
The reaction was car- ard and the results are reported in Table 1. They are
ried out in a two-phase system, water-CH Cl , with the the average of at least three independent runs. Chloro-
2
2
oxybromination reagents dissolved in water and the sub- form was also used as organic solvent. The conversion
strate dissolved in the organic solvent. It is characterized of ethynylbenzene and yields were determined inde-
by a good overall yield and a good selectivity toward the pendently and were in good agreement for the reaction
formation of the synthetically valuable bromohydrin. in dichloromethane, where 1,2-dibromostyrene (cisþ
Table 1. Mo(VI)-catalysed oxybromination of ethynylbenzene with hydrogen peroxide and KBr in water/halogenated solvent.
ꢀ
Entry Solvent [PhC¼CH] [MoO4 ], [KBr] [H O ] Time Conversion Relative Absolute Selectivity
2
2
[a]
[b]
[c]
[
M]
[M]
[M]
[M]
[h]
[%]
yield
yield
A : B : C : D
1
2
3
CH Cl2 0.01
0.005
0.01
0.01
0.05
0.025
0.025
0.01
0.02
0.02
18
18
18
50
50
50
84%
94%
64%
42%
47%
32%
20: 56: 20: 4
11: 31: 7: 51
11: 25: 15: 49
2
CH Cl2 0.02
2
CHCl3
0.02
[
[
[
a]
Time necessary for the oxidant to be consumed.
Relative to the consumed substrate.
Relative to the initial concentration of alkyne.
b]
c]
Adv. Synth. Catal. 2005, 347, 1341–1344
DOI:10.1002/adsc.200505114
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1341

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Table 2. Mo(VI)-catalysed oxybromination of ethynylbenzene with hydrogen peroxide and KBr in water/ionic liquids.
ꢀ
[a]
Entry Solvent
[PhC¼CH] [MoO4
]
[KBr] [H O ] Time [h]
Conversion Relative Absolute Selectivity
[c] [d]
2
2
[
M]
[M]
[M]
[M]
[%]
yield
yield
A : B : C : D
[
b]
1
2
3
4
5
bmim Tf N
0.02
0.04
0.02
0.04
0.04
0.01
0.02
0.01
0.02
0.02
0.10
0.05
0.10
0.05
0.10
0.02
0.04
0.02
0.04
0.04
2
4
2
2
2
50
40
55
50
60
64%
80%
96%
92%
95%
32%
32%
53%
46%
57%
3 : 8 : 43: 46
4 : 6 : 24: 66
0 : 7 : 19: 74
2 : 4 : 16: 78
2 : 7 : 38: 53
2
bmim Tf N
2
bmim PF6
bmim PF6
bmim PF6
[
[
[
[
a]
Time necessary for the oxidant to be consumed.
b]
c]
d]
Tf N¼(CF SO ) N.
2
3
2 2
Relative to the consumed substrate.
Relative to the initial concentration of alkyne.
Table 3. Oxybromination of ethynylbenzene with hydrogen peroxide added batchwise and KBr in H O/bmim PF .
2
6
[a]
Entry
[PhC¼CH]
M]
Catalyst
[Catalyst]
[M]
[KBr]
[M]
[H O ]
[M]
Conversion
[%]
Absolute
yield
Selectivity
A : B : C : D
2
2
[
b]
[
ꢀ
1
2
0.02
0.02
MoO
VO3
0.01
0.02
0.1
0.1
0.04
0.04
100
100
88%
70%
6: 9: 10: 75
13: 15: 9: 63
4
ꢀ
[
[
a]
b]
Added in two portions.
Relative to the initial concentration of alkyne.
trans mixture) was the main product and the overall into the reaction products. Second, yields were compa-
yield was around 50%. In chloroform, the amount of rable, but the selectivity was definitely shifted toward
ethynylbenzene that disappeared was higher than that the dibromo ketone (Table 2).
transformed into brominated products, probably due
This is an important result, because a,a-dibromoace-
to side reactions. At the same time, a parallel decompo- tophenone is important per se, having antibacterial, fun-
sition of H O can occur upon prolonged contact with gicidal and algicidal properties, as evidenced by a num-
2
2
[
4,8]
[10]
Mo(VI), as it was observed with V(V) species. Initial ber of patents. Moreover, it is a valuable intermediate
reaction conditions were chosen in order to favour the for further transformations, for example, to a-haloeno-
[
11]
[12]
formation of molecular bromine (entry 1) or to disfa- lates or biologically active heterocyclic compounds.
vour it (entry 2). As can be seen from inspection of Ta- The synthesis of a,a-dihaloacetophenones still needs
ꢀ
ble 1, an increase of the alkyne/Br ratio from 0.2 to improvement and new procedures were recently report-
[
12,13]
0
.8 – consequently diminishing the reagent that gives di- ed.
bromo derivatives – shifted the selectivity toward a,a- In order to improve the yield, experiments were car-
dibromoacetophenone. This result indicates that bro- ried out by adding H O in two portions, in order to
2
2
moalkenes and bromo ketones are formed by different keep its decomposition at a minimum. As can be seen
routes. If we compare the reactions in dichloromethane from Table 3, yield rose up to 88%, while selectivity re-
and chloroform, other conditions being equal, selectivi- mained the same (entry 1). The reaction was repeated
ties are comparable, although the yield is somewhat low- with the same procedure, i.e., batchwise addition of
er in chloroform than in CH Cl (entries 2 and 3).
H O , using V(V) as catalyst. As expected, yields were
2 2
2
2
The reaction was then performed in water/ionic liq- lower (Table 3, entry 2), although still good, with a sim-
uids, in order to verify whether it was possible to replace ilar product distribution.
the halogenated solvent with a more sustainable one.
In order to understand how a,a-dibromoacetophe-
Hydrophobic ILs with the 1-butyl-3-methylimidazolium none formed, a blank experiment was performed, start-
þ
[
bmim ] cation were used, with different anions, i.e., ing from a-bromoacetophenone [Eq. (1)]. Under the
ꢀ
hexafluorophosphate, [PF6 ], and bis(trifluorometh- same conditions, no reaction was observed. Therefore,
anesulfonyl)imide, [(CF SO ) N ]. The results are the formation of the dibromo derivative must occur af-
ꢀ
[9]
3
2 2
collected in Table 2.
ter the first addition to the triple bond, before the bro-
A numberof interesting aspects emerged. First, the re- moenol transforms into a-bromo ketone.
action performed in water/ILs was faster than that in
molecular solvents. The reduced reaction times, espe-
cially in bmim PF , had the positive side effect that al-
(1)
6
most all the consumed ethynylbenzene was converted
1342
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Oxybromination of Ethynylbenzene
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Scheme 2. Reaction pathways of the Mo(VI)-catalyzed oxybromination of ethynylbenzene.
The pathways of ethynylbenzene oxybromination are compares favourably with previously reported synthesis
[
16]
represented in Scheme 2, in analogy to what was found of a,a-dibromoacetophenone. The system made of
[
5]
in alkene oxybromination. for which reactive species Mo(VI)/KBr/H O is a mild, efficient and sustainable
2
2
[
14]
were experimentally detected.
catalyst for alkynes as well as for alkenes.
This mechanistic scheme is in agreement with the ex-
perimental results. In fact, the sharp decrease of 1,2-di-
bromostyrene on going from dichloromethane to
Experimental Section
bmimPF can be ascribed to different distribution of mo-
6
lecular bromine between the two phases. In the ionic liq-
[
15]
uid, a more polar medium, where the functionalisa-
General Methods
[
5]
tion of the substrate is likely to occur, the Br concen-
2
GC analyses were carried out with a Varian CP 3900 instru-
ment, equipped with a 30 mꢁ0.25 mm SPB 35 capillary col-
umn, coated with 0.25 mm methylsilicone. A Bruker AM400
spectrometer was used to obtain H NMR spectra, as CDCl3
solutions, with tetramethylsilane as the internal standard.
Mass spectra were obtained with a GC-MS Shimadzu CP
tration is expected to be lower than in dichloromethane.
Moreover, the very nature of the IL may help in keeping
the reactive species within the organized solvent cage,
thus rendering the reaction faster.
1
In conclusion, the oxybromination reaction by H O /
2
2
KBr was successfully applied to an alkyne. The catalysis
by Mo(VI) was more effective than that by V(V). The
6
000 instrument. IR spectra were recorded with a Perkin-El-
mer 983 spectrophotometer, using an NaCl cell and CCl as
4
conversion of ethynylbenzene could be made almost the solvent.
quantitative, just by adding H O in portions. Finally,
2
2
the selectivity could be diverted from the 1,2-dibromoal-
kene to the synthetically useful dibromo ketone, by Preparation of Ionic Liquids
changing the solvent from dichloromethane to ionic liq-
The synthesis of ILs used in this work consisted in two steps.
uid.
Work is in progress to extend the reaction to other al-
kynes and to elucidate factors affecting the mechanism.
The first was a quaternisation reaction between an alkyl-substi-
tuted imidazole and an alkyl bromide, to obtain a solid precur-
sor. The second one was a metathesis reaction in which the bro-
However, it is already possible to say that in H O/IL, mide ion is exchanged by an appropriate anion able to give a
2
provided that H O is added batchwise, the method liquid product at room temperature. Both these processes
2
2
Adv. Synth. Catal. 2005, 347, 1341–1344
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Valeria Conte et al.
[
17–21]
were executed following literature procedures.
Charac- References
1
terization of ionic liquids was made by H NMR and their iden-
tity was confirmed bycomparison with literature data, where
available.
[
22]
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5, 7429.
1
,2-Dibromostyrene (cisþtrans) was prepared in 22% yield by
[
[
[
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2
2
KBr and 1.2 mmol KBrO in 30 mL water, with the pH adjust-
3
ed at 1.0 (HClO ), until the reddish-brown colour disappeared.
4
a-Bromoacetophenone is a commercial grade reagent. a,a-
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phy from the crude reaction product (silica gel; eluent: 40–
7
08C petroleum ether containing 5% diethyl ether); IR:
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1 1
nCO ¼1750 cm ; H NMR (CDCl ): d¼8.1 (broad s, 5H, Ph),
3
6
.55 (s, 1H, CHBr ).
2
Four solutions in CHCl , containing a known concentration
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3
of decane (0.01 M) as the internal standard, were prepared for
each compound (ethynylbenzene, 1,2-dibromostyrene, a-bro-
moacetophenone, a,a-dibromoacetophenone), with concen-
trations in the range 0.002 to 0.02 M). The solutions were in-
jected in the gas-chromatograph at least three times each and
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plotted against the concentration ratios. The slope of the
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1
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[
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1
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1
Oxybromination of Ethynylbenzene
Baker, German Patent DE 71–2156625 19711115, 1972;
Chem. Abstr. 1972, 77, 122996.
In water-organic solvent: In a typical experiment, 1 mmol KBr
and 0.4 mmol (NH ) (MoO ) were dissolved in 40 mL H O and
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4
2
4
2
the pH adjusted at 1.0 with HClO . 0.8 mmol ethynylbenzene
4
were dissolved in 40 mL CH Cl . The two solutions were mixed
2
2
in an Erlenmeyer flask, stirred at 1000 rpm, and 0.8 mmol hy-
drogen peroxide added. The reaction was stopped as soon as
the yellow colour of diperoxomolybdenum disappeared. The
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[
(
MoO ) were dissolved in 10 mL H O and the pH adjusted at
4
2
1
.0 with HClO . 1 mL of this solution was added in a Schlenk
4
[
[
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2
002, 187, 215.
0
.02 mmol H O added. At the end of the reaction (disappear-
2 2
[
[
[
[
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ance of yellow colour), 100mL of the ionic liquid solution were
taken and diluted in 1 mL CHCl , 0.01 M in dodecane. The sol-
3
ution was examined by GC.
Acknowledgements
2
002, 2831.
Financial support fromMIUR, PRIN 2003 Project “Develop-
ment of new recyclable catalysts for oxidation processes with hy-
drogen peroxide” is gratefully acknowledged.
1344
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asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 1341–1344