Direct sustainable bromination of alkenes in aqueous media and basic ionic liquids

Article abstract of DOI:10.1016/j.tetlet.2013.05.097

Electron-rich and electron-poor alkenes have been dibrominated using a rapid and sustainable procedure. The reactions were conducted in aqueous medium and basic ionic liquids which catalyzed the direct addition of bromine. The protocol leads to remarkable results, high yields under mild conditions, complete chemo- and stereo-selectivity and allows the recycling of ionic liquids, reducing costs, and environmental impact.

Full text of DOI:10.1016/j.tetlet.2013.05.097

Accepted Manuscript
Direct sustainable bromination of alkenes in aqueous media and basic ionic liq‐
uids
Patrizia Primerano, Massimiliano Cordaro, Angela Scala
PII:
S0040-4039(13)00876-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.05.097
TETL 42997
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
10 April 2013
14 May 2013
22 May 2013
Please cite this article as: Primerano, P., Cordaro, M., Scala, A., Direct sustainable bromination of alkenes in aqueous
media and basic ionic liquids, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.05.097
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Graphical Abstract
Direct sustainable bromination of alkenes in
aqueous media and basic ionic liquids
Patrizia Primerano,* Massimiliano Cordaro and Angela Scala

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Direct sustainable bromination of alkenes in aqueous media and basic ionic liquids
a,
b
b,c
Patrizia Primerano  , Massimiliano Cordaro and Angela Scala
a
Dipartimento di Ingegneria Elettronica, Chimica e Ingegneria Industriale, Contrada di Dio, Messina 98166, Italy.
Dipartimento di Scienze Chimiche, Viale F. Stagno D’Alcontres 31, Messina 98166, Italy
CNR-ISMN Istituto per lo Studio dei Materiali Nanostrutturati, V.le F. Stagno d'Alcontres 31, 98166, Messina
b
c
ARTICLE INFO
ABSTRACT
Article history:
Received
Electron-rich and electron-poor alkenes have been dibrominated using a rapid and sustainable
procedure. The reactions were conducted in aqueous medium and basic ionic liquids which
Received in revised form
Accepted
Available online
catalyzed the direct addition of bromine. The protocol leads to remarkable results, high yields in
mild conditions, complete chemo-and stereo-selectivity and allows the recycling of ionic liquids,
reducing costs and environmental impact.
Keywords:
Bromination
Ionic liquid
2
009 Elsevier Ltd. All rights reserved.
Alkenes
Sustainable synthesis
Stereoselective
Vicinal dibromoalkanes are important compounds widely
applicable as versatile synthetic intermediates in a considerable
promoted. Recently, specific ILs, where the anionic part consists
-
of Br , which combine simultaneously solvent and halogenating
3
1,2
11
number of useful transformations and for the protection-
properties, have been successfully used as a new more
3
a
deprotection of olefines. In analytical chemistry the high
selectivity and sensitivity of their formation is fully exploited as a
diagnostic test for alkenes and alkynes and for their
affordable alternative. However, also this procedure, despite the
undoubted improvement compared to the previous ones, is not
completely free from the limitations discussed above and,
moreover, it is time consuming. A comparison among the known
methods of bromination of alkenes and a determination of their
13
3
determination in different complex matrixes. Traditionally, they
are performed by using molecular bromine in chlorinated
4
12
solvents, but, unfortunately, this procedure is highly polluting.
environmental impacts in agreement to the Sheldon factor,
Moreover, the process in water is not practicable, except special
cases, due to the poor control of this reaction and the
however, have not ruled out at all that the direct addition of
molecular bromine to the unsaturated substrate still can be
considered a reasonable option for this reaction, especially if a
significant environmental improvement could be reached. In this
article, we present the results of bromination of alkenes in water
in the presence of amino-functionalized ionic liquids 1 and 2
5
contamination of the final products. Indeed, in water, the
bromination is very fast, leading to a significant amount of
bromohydrins, due to the competitive nucleophilic attack of
6
water on the intermediate bridge. More recently, in this context,
1
4
efforts to find new sustainable alternatives are directed primarily
to circumvent the use of liquid bromine as reagent to avoid its
hazardous potential. Procedures of bromination in-situ by
oxidative reactions under various homogeneous and
(Figure 1), such as promising sustainable procedure.
7
heterogenous reaction conditions or the use of suitable
bromination agents as pyridiniumbromide-ammonium quaternary
8
or tribromide perbromide (OATB) agents have been recently
described. These new methods of bromination have yet revealed
limitations, due, for example, to possible environmental
contamination from metals used or to low atom-economy,
respectively, as well as to the impossibility in many cases to
renounce the use of organic solvents. In addition, the use of
Figure 1. Basic ionic liquids (BILs)
1
5
Since the polarizability of the molecule of Br with amines is
2
well-known, Basic Ionic Liquids (BILs) 1 and 2, incorporating an
amine moiety (Fig. 1), were prepared according to literature
procedure, so they can be used as dual solvent-catalyst.
Unfortunately, preliminary tests of addition of bromine to styrene
suitable solvents as benign reaction media including ionic liquids
1
6
9
(
ILs), which are non-volatile and can provide non-aqueous
1
0
reaction media of varying polarity and easily can be reused, was
—
——

Corresponding author. Tel.: +39-090-393134; fax: +39-090-391518; e-mail: patrizia.primerano@unime.it

2
Tetrahedron Letters
3
a (Table 1) in BILs 1a and 2a were not satisfactory, probably
Starting from alkene 3a, the proposed procedure produces the
expected vic-dibromo derivative 4a (Table 1), which was isolated
in 93% yield by simple filtration, without development of
hydrobromic acid. The reaction is clear, simple and efficient and,
significantly, occurs without oxygenated by-products and not in
due to excessive viscosity of the BILs, which prevented a proper
homogeneity of the reaction. Addition of water (ratio
BIL/water=1:3) in all cases dramatically improved the reaction
yield, likely making more homogeneous and less dense the
reaction mixture. Therefore, the ratio between the components,
reaction time and temperature were examined, in order to
improve the yield of the process. Usually, the bromination
process, using all types of BILs, is complete after 30 minutes at
room temperature (25 °C). Subsequently, the effect of the amount
of the BILs 1a and 2a was evaluated and in both cases the yield
reaches its maximum when 30% BIL was used. Increasing the
amount of BIL, the yield is only slightly changed, therefore, 30%
is the right value related to the implementation costs. However,
reducing the amount of BIL, constant loss of efficiency and
control of the reaction is observed, as known for the
1
7
darkness. The addition of bromine was performed by syringe,
putting the needle directly in the reaction mixture to prevent the
spread of the highly toxic gaseous bromine. Therefore, it is
noteworthy that the water does not interfere on the final product,
1
8
rather it accelerates the progress of the reaction. Tests
performed using BILs 1b,c and 2b,c have expressed basically the
same trend, showing that the amine moiety reasonably plays a
crucial role in this process. Therefore, the BIL 1a was chosen as
model one for further investigations extended to other alkenes
3b-k (Table 1).
Rates, yields and high selectivity are similar, compared with
previous methods, moreover, our procedure appears to be better
in terms of atom economicity and environmental sustainability.
The 1:1 stoichiometric ratio of alkene and bromine was
maintained constant for all experiments, except for ethylenic
compounds 3c and 3d totally insoluble in the reaction mixture,
where excess of Br (ethylenic compounds/Br 1:3) was used to
6
brominations carried out only in water.
Table 1. Bromination data of alkenes 3
2
2
increase their solubility, instead of using an organic co-solvent.
Generally, diversely substituted alkenes 3b-f, with final or
internal or endo-cyclic C=C bond, provide very satisfactorily the
expected vic-dibromo derivatives 4b-f with complete
stereoselectivity and anti-addition process. For example, trans
1
,2-dibromo-cyclopentane 4e and 1,2-dibromo–cyclohexane 4f
are the only isolated products, respectively from cyclopentene 3e
and cyclohexene 3f. Similarly, the dibromo products 4c and 4d
from trans-stilbene 3c and norbornene 3d have the meso and d,l-
configuration, respectively, in line with an anti-addition to the
C=C bond. The olefins 3g-k coniugated with a carbonyl group,
showed similar trends and high yields of the corresponding
products of erythro-dibromination. The reaction is highly
chemoselective, thus none relevant by-products, due to attacks on
other portions of the olefin, have been isolated.
In scheme 1, we propose a possible mechanism for the
formation of the dibromo derivatives 4a-k that would motivate
the absence of by-products as halohydrins or epoxides and the
stereoselective formation of dibromo derivatives. Therefore, we
suppose that the bromine, is first trapped by BIL, evolving to the
Mulliken’s ―inner‖-type complex 5, according to a recent
2
5
report, rather than be fixed to the unsaturated compound 3 to
2
6
give the classic intermediate bridge. Then, 5 evolves with the
2
7
unsaturated compound 3 in a concerted process providing the
transition state 6, which directly leads to dibromo-derivative 4,
without any bromonium ion intermediate, releasing the BIL,
which can repeat the catalytic cycle.
Scheme 1. Proposed mechanism by Mulliken’s complex 5
Finally, it is noteworthy that the BIL catalyst can be recovered
and directly reused for efficiency tests without further work-up,
after separation of products 4 by filtration. Products liquids are
extracted in ethyl acetate where BIL 1a is not dissolved. The
results of three subsequent runs with BIL 1a and selected alkenes
highlighted a gradual decrease in activity, but quite acceptable.

3
In conclusion, a novel one-pot method for chemo-and
diastereo-selective dibromination of electron-rich and electron-
poor alkenes has been developed in aqueous medium. By using
targeted ILs functionalized with a basic amino-aliphatic chain as
catalysts, a simple procedure was accomplished with low
environmental impact, without using organic solvents and with
the possibility of recycling ionic liquids and reducing the cost
of production. Thus, this method appears as a better and useful
alternative to the existing procedures and can display a promising
potential for further applications.
1
Compound 1c, 730 mg (91%): H NMR, (300 MHz, CDCl
3
): δ
H
References and notes
8
2
.72 (s, 1H); 7.45 (s, 1H); 7.32 (s, 1H); 4.16 (t, 2H); 3.90 (s, 3H);
13
.73 (t, 2H); 2.47 (q, 4H); 0.85 (t, 6H). C NMR, (75MHz,
): δ 135.9, 122.6, 122.3, 51.8, 47.7, 46.1, 35.7, 10.9.
(281.114): calcd. C 42.63; H 7.16; N 14.91; found
C 42.69; H 7.20; N 15.02.
Compound 2a, 610 mg (93%): H NMR, (300 MHz, CDCl
8.51 (s, 1H); 7.40 (s, 1H); 7.26 (s, 1H); 4.14 (m, 4H); 2.74 (t, 2H);
1
2
3
.
.
.
(a) Holzweber, M.; Schnürch, M.; Stanetty, P. Synlett 2007, 19,
CDCl
3
C
3
3
3
016-3018; (b) Gribble, G. W. Chem. Soc. Rev. 1999, 28, 335-
46; (c) Kutsumura, N.; Niwa, K.; Saito, T. Org. Lett. 2010, 12,
316-3319 and references here reported; (d) Kuang, C.; Yang, Q.;
10 3 4
C H20ClN O
1
3
): δ
H
Senboku, H.; Tokuda, M. Tetrahedron 2005, 61, 4043-4052.
(a) Maji, T.; Karmakar, A.; Reiser, O. J. Org. Chem. 2011, 76,
1
3
2.49 (q, 4H); 1.81 (m, 2H); 1.31 (m, 2H); 0.89 (m, 9H). C NMR,
(75MHz, CDCl ): δ 136.0, 122.9, 121.4, 52.5, 49.4, 48.2, 46.0,
31.9, 18.8, 13.4, 11.0. F NMR, (470 MHz, CDCl
7
36-739 and references here reported; (b) Lee, S. H.; Chang, Y.
M.; Yoon, C. M. Bull. Korean Chem. Soc. 2004, 25, 1723-1725;
c) Totten, L. A.; Jans, U.; Roberts, A. L.; Environ. Sci. Technol.
001, 35, 2268-2274.
(a) Ranu, B. C.; Guchhait, S. K.; Sarkar, A. Chem. Commun.
998, 2113-2114 and references cited therein; (b) Delaet, M.;
3
C
19
3
): δ
F
–72.27 (d,
1
(
2
J=755.0 Hz). C13H F N P (281.114): calcd. C 42.28; H 7.10; N
26 6 3
11.38; found C 42.39; H 7.30; N 11.52.
1
Compound 2b, 670 mg (92%): H NMR, (300 MHz, CDCl
3
): δ
H
1
8.76 (s, 1H); 7.46 (s, 1H); 7.31 (s, 1H); 4.17 (m, 4H); 2.74 (t, 2H);
13
Tilquin, B. Talanta 1992, 39, 769-773; (c) Irgolic, K. J. In
Houben-Weyl, 4th ed., Vol. E12b; Klamann, D., Ed.; Thieme:
Stuttgart 1990, 150.
House, H. O. Modern Synthetic Reactions, 2nd edn., W. A.
Benjamin. Inc., 1972, 263-274.
(a) Becker, H. G. O. Organikum: Organisch-chemisches
Grundpraktikum, 21st ed., 3–527–29985–8, Wiley-VCH,
Weinheim 2001, 298-301; (b) Rhinesmith, H. S. Org. Synth. 1943,
2.48 (q, 4H); 1.82 (m, 2H); 1.32 (m, 2H); 0.89 (m, 9H). C NMR,
(75MHz, CDCl ): δ 135.7, 122.7, 121.5, 52.2, 49.3, 48.0, 46.4,
31.7, 19.1, 13.1, 11.4. F NMR, (470 MHz, CDCl
(311.216): calcd. C 50.18; H 8.42; N 13.50; found C
50.31; H 8.50; N 13.60.
Compound 2c, 730 mg (92%): H NMR, (300 MHz, CDCl
8.86 (s, 1H); 7.49 (s, 1H); 7.31 (s, 1H); 4.21 (m, 4H); 2.77 (t, 2H);
3
C
19
3
): δ –151.20.
4
5
.
.
13 4 3
C H26BF N
1
3 H
): δ
1
3
2.51 (q, 4H); 1.85 (m, 2H); 1.35 (m, 2H); 0.88 (m, 9H). C NMR,
(75MHz, CDCl ): δ 135.4, 122.4, 121.3, 51.7, 49.0, 47.7, 46.1,
31.4, 18.7, 12.8, 11.1. C13 (323.161): calcd. C 48.22; H
2
, 177.
3
C
6
7
.
.
Zefirov, N. S.; Koz’min, A. S.; Dan’kov, Y. V.; Zhdankin, V. V.;
Kirin, V. N. Zhur. Org. Kim. 1984, 20, 233-242.
(a) Podgoršek, A.; Zupan, M.; Iskra, J. Angew. Chem. Int. Ed.
3 4
H26ClN O
8.09; N 12.98; found C 48.29; H 8.20; N 13.05.
17. Schonberg, A., Preparative Organic Photochemistry, Springer-
Verlag: New York 1968; Chapter 37.
18. Simon M. O.; Li C.-J. Chem. Soc. Rev. 2012, 41, 1415-1427.
19. Kavala, V.; Naik, S.; Patel, B. K. J. Org. Chem. 2005, 70, 4267-
4271.
20. (a) Yonehara, K.; Kamata, K.; Yamaguchi K.; Mizuno, N. Chem.
Commun. 2011, 47, 1692-1694. (b) Adimurthy, S.; Ghosh, S.;
Patoliya, P. U.; Ramachandraiah, G.; Agrawal, M.; Gandhi, M. R.;
Upadhyay, S. C.; Ghosh P. K.; Ranu B. C. Green Chem. 2008, 10,
232-237.
21. Subramanian, P. M.; Emerson M. T.; Lebel, N. A. J. Org. Chem.
1965, 30, 2624-2634.
22. Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H., Curran, D. P. J.
Am. Chem. Soc. 2002, 124, 12946-12947.
23. Das, B.; Srinivas, Y.; Sudhakar, C.; Damodar K.; Narender, R.
Synth. Commun. 2009, 39, 220-227.
24. Typical experimental procedure: In a 25 ml flask containing BIL
1a (30%) and water (5 ml), pure alkene 3 (3.0 mmol) was added,
2
2
009, 48, 8424-8450; (b) Ye, C.; Shreeve, J. M. J. Org. Chem.
004, 69, 8561-8563 and references here reported; (c) de Almeida,
L. S.; Esteves, P. M.; de Mattos, M. C. S. Synlett 2006, 10, 1515-
518; (d) Shao, L. X.; Shi, M. Synlett 2006, 1269-1271.
Pavlinac, J.; Zupan, M.; Laali, K.; Stavber, S. Tetrahedron 2009,
5, 5625-5662 and references here reported.
(a) Harjani, J. R.; Nara, S. J.; Salunkhe, M. M. Tetrahedron Lett.
002, 43, 1127-1130; (b) Namboodiri, V. V.; Varma, R. S. Chem.
Commun. 2002, 342-343; (c) Qiao, K.; Yokoyama, C. Chem. Lett.
004, 33, 472-473.
1
8
9
.
.
6
2
2
1
0. (a) Welton, T. Chem. Rev., 1999, 99, 2071-2084; (b)
Wasserscheid, P., Keim, W. Angew. Chem., Int. Ed. 2000, 39,
3
773-3789; (c) Sheldon, R. Chem. Commun. 2001, 2399-2407;
(d) Wilkes, J. S. Green Chem. 2002, 4, 73-80; (e) Yao, Q. Org.
Lett. 2002, 4, 2197-2199; (f) Zerth, H. M.; Leonard, N. M.;
Mohan, R. S. Org. Lett. 2003, 5, 55-57; (g) Su, C.; Chen, Z.-C.;
Zheng, Q.-G. Synthesis 2003, 555-559; (h) Rajagopal, R.; Jarikote,
D. V.; Lahoti, R. J.; Daniel, T.; Srinivasan, K. V. Tetrahedron
Lett. 2003, 44, 1815-1817; (i) Kumar, A.; Pawar, S. S. J. Org.
Chem. 2004, 69, 1419-1420.
2
maintaining the temperature between 10°-20°C. Then, Br (3.0
mmol) was added dropwise by a syringe under continuous stirring
as rapidly as the colour is destroyed. After all the bromine has
been added, the resulting reaction mixture was stirred for an
additional 15 minutes at room temperature. Solid compounds 4
were filtrated and purified by crystallization, while the remaining
BIL/water solution was ready for reusing. Conversely, an
extraction using ethyl acetate was carried out to separate not solid
dibromide derivatives 4 from the mixture. The combined organic
extract was washed with water and dried over anhydrous sodium
sulfate, while the remaining solution (BIL/water) was ready for
reusing as above. After evaporation of ethyl acetate the crude
product was purified by flash chromatography over silica gel
(ethane-diethyl ether 9:1). All products 4a-k are identified with
their appropriate stereoconfiguration (wherever applicable) by
1
1. (a) Cristiano, R.; Ma, K.; Pottanat, G.; Weiss, R. G. J. Org. Chem.
2
009, 74, 9027-9033 and references here reported; (b) Chiappe,
C.; Capraio, D.; Conte, V.; Pieraccini, D. Org. Lett. 2001, 3, 1061-
063.
1
1
1
2. Eissen M.; Lenoir, D. Chem. Eur. J. 2008, 14, 9830-9841.
3. (a) Sheldon, R. A. Green Chem. 2007, 9, 1273-1283; (b) Sheldon,
R. A. Chem. Ind. 1992, 23, 903-906.
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Trans II 1987, 2, 39-45.
6. (a) Zhang, Y.; Xia, C. Applied Catalysis A: General 2009, 366,
1
1
1
7a,19-23
comparison with authentic samples.
1
41-147; (b) Ye, C.; Xiao, J. C.; Twamley, B.; La Londe, A. D.;
Norton, M. G.; Shreeve, J. M. Eur. J. Org. Chem. 2007, 30, 5095-
100.
Selected Data. Compound 1a, 780 mg (92%): H NMR, (300
MHz, CDCl ): δ 8.54 (s, 1H); 7.41 (s, 1H); 7.22 (s, 1H); 4.15 (t,
H); 3.90 (s, 3H); 2.78 (t, 2H); 2.53 (q, 4H); 0.91 (t, 6H).
NMR, (75MHz, CDCl ): δ 136.3, 122.9, 122.8, 52.3, 48.3, 46.7,
6.1, 11.5. F NMR, (470 MHz, CDCl
Hz). C10 P (327.130): calcd. C 36.70; H 6.16; N 14.84;
found C 36.79; H 6.20; N 14.90.
25. Karpfen, A. Struct. Bond 2008, 126, 1-15 and references here
cited.
26. (a) Chretien, J. R.; Coudert, J.-D.; Ruasse, M.-F. J. Org. Chem.
1993, 58, 1917-1921; (b) Bellucci, G.; Chiappe, C.; Lo Moro, G.
J. Org. Chem. 1997, 62, 3176-3182.
5
1
3
H
13
2
C
27. Chiappe, C.; Pieraccini, D. J. Org. Chem. 2004, 69, 6059-6064.
3
C
1
9
1
3
3 F
): δ –72.30 (d, J=755.0
20 6 3
H F N
1
Compound 1b, 670 mg (95%): H NMR, (300 MHz, CDCl
3
): δ
H
8
2
.70 (s, 1H); 7.44 (s, 1H); 7.31 (s, 1H); 4.16 (t, 2H); 3.90 (s, 3H);
1
3
.75 (t, 2H); 2.49 (q, 4H); 0.88 (t, 6H). C NMR, (75MHz, 1
9
CDCl
NMR, (470 MHz, CDCl
calcd. C 44.63; H 7.49; N 15.62; found C 44.69; H 7.50; N 15.70.
3
): δ
C
136.5, 123.1, 122.7, 52.3, 48.0, 46.6, 35.9, 11.4.
F
3
): δ –151.22. C10 (269.169):
F
4 3
H20BF N

Figure 1

GraphAbstr

Scheme 1

Table(s)