Stereoselective halogenations of alkenes and alkynes in ionic liquids

Article abstract of DOI:10.1021/ol015631s

(matrix presented) Room-temperature ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium bromide, and 1-butyl-3-methylimidazolium chloride, are used as "green" recyclabl

Full text of DOI:10.1021/ol015631s

ORGANIC
LETTERS
2001
Vol. 3, No. 7
1061-1063
Stereoselective Halogenations of
Alkenes and Alkynes in Ionic Liquids
,†
Cinzia Chiappe,* Dario Capraro,† Valeria Conte,‡ and Daniela Pieraccini†
Dipartimento di Chimica Bioorganica e Biofarmacia, UniVersita` di Pisa,
Via Bonanno 33, 56126 Pisa, Italy, and I.P.P.A. Facolta` di Agraria,
UniVersita` di Foggia, Via Napoli 25, 71100 Foggia, Italy
cinziac@farm.unipi.it
Received January 30, 2001
ABSTRACT
Room-temperature ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-
methylimidazolium bromide, and 1-butyl-3-methylimidazolium chloride, are used as “green” recyclable alternative to chlorinated solvents for
the stereoselective halogenation of alkenes and alkynes.
Room-temperature ionic liquids that are air and moisture
stable have been subjected to an increasing number of
scientific investigations,1-3 and their application as novel
solvent systems for organic synthesis has received in the last
years a good deal of attention.3 The reactions carried out in
ionic liquids have a different thermodynamic and kinetic
behavior with respect to those in conventional solvents, and
in addition, ionic liquids have a number of properties that
may be of importance for industrial application. In particular,
their lack of measurable vapor pressure characterizes them
as media for green synthesis.1 Room-temperature ionic
liquids have been reported as solvents for a number of
reactions such as dimerization of alkenes,4 Friedel-Crafts
reactions,5 Diels-Alder cycloadditions,6 and hydrogenation
reactions7 and more recently have been introduced in the
Heck reaction8 and in the asymmetric epoxidation using a
chiral (salen)Mn as catalyst.9 At variance with the electro-
philic substitutions of aromatic compounds, which have been
extensively investigated in chloroaluminate(III) ionic liquids,3
with the exception of a recent patent10 no data have been
reported for the electrophilic halogen addition reactions to
alkenes and alkynes.
Dihalo derivatives are important compounds in the organic
synthesis as well as in analytical chemistry. As an example,
the selective determination of alkenes in complex hydrocar-
bon mixtures, such as air, gasolines etc., by GC-flame
ionization detection is indeed difficult. Analysis of alkenes
in the presence of alkanes may be however achieved after
their transformation into the corresponding dibromo-deriva-
tives using saturated aqueous bromine.11 More recently, a
selective and sensitive method for alkenes determination in
† Universita` di Pisa.
‡ Universita` di Foggia.
(1) Holbrey, J. D.; Seddon, K. R. Clean Products Processes 1999, 1,
223. Earle, M. J.; Seddon, K. R. Pure Appl. Chem. 2000, 72, 1391.
(2) Armstrong, D. W.; He, L.; Liu, Y. S. Anal. Chem. 1999, 71, 3873.
(3) Welton, T. Chem. ReV. 1999, 99, 2071.
(4) Dullius, J. E. L.; Suarez, P. A. Z.; Einloft, S.; de Souza, R. F.; Dupont,
J.; Fisher, J.; De Cian, A. Organometallics 1988, 7, 815.
(5) Boon, J. A.; Levisky, J. A.; Pflug, J. L.; Wilkes J. S. J. Org. Chem.
1986, 51, 480.
(7) Chauvin, Y.; Mussmann, L.; Oliver, H. Angew. Chem., Int. Ed. Engl.
1995, 34, 2698.
(8) Carmichael, A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.;
Seddon, K. R. Org. Lett. 1999, 1, 997.
(9) Song, C. E.; Ro, E. J. Chem. Commun 2000, 837.
(10) Winterton, N.; Seddon, K. R.; Patell, Y. PCT Int. Appl. Patent
WO2000037400, 2000; Chem. Abstr. 2000, 133, 75627.
(11) Delaet, M.; Tilquin, B. Talanta 1992, 39, 769.
(6) Horwarth, J.; Hanlon, K.; Fayne, D.; McCormac P. B. Tetrahedron
Lett. 1997, 38, 3097
10.1021/ol015631s CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/13/2001

Scheme 1
Table 1. Product Distribution for Br2 Addition to 1, 2, 5, 8, 9,
and 13 in [bmim][Br] at Room Temperature.
substrate
yielda (%)
products
ratiob
1a
1b
1c
1d
2a
2b
2c
2d
5a
5b
5c
5d
5e
8
95
95
93
90
95
93
93
93
94
96
96
96
97
95
95
93
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
6 + 7
6 + 7
6 + 7
6 + 7
6 + 7
10 + 11
10 + 12
15 + 16
>99:1
>99:1
>99:1
>99:1
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
>99:1
>99:1
20:80
9
13
1
a Isolated yields. b Determined by H and 13C NMR
room temperature was examined in 1-butyl-3-methylimida-
zolium hexafluorophosphate, [bmim][PF6], 1-butyl-3-meth-
ylimidazolium tetrafluoroborate, [bmim][BF4], and 1-butyl-
3-methylimidazolium bromide, [bmim][Br]. The products
were always conveniently extracted with Et2O and analyzed
by NMR (Scheme 1).
Reactions are typically carried out by adding, with stirring,
1 equiv of unsaturated compound to a 0.3 M solution of Br2
in the ionic liquid.13 In alkene and diene bromination,
complete consumption of the reagents was observed in less
than 1 min, longer times were necessary for alkyne bromi-
nation in particular when the reactions were carried out in
[bmim][Br]. The dibromo adducts were identified on the
different complex matrixes has been obtained by using a GC
analysis with element-selective plasma spectroscopic detec-
tion of the dibromo derivatives.12 In such a procedure,
halogen addition is carried out in CCl4, one of the chlorinated
solvents extensively used for this type of reactions. These
solvents, however, are currently on the “environmental
blacklist”. Furthermore, in CCl4 the electrophilic additions
are slow and radical reactions, bearing to a different product
distribution, may occur. On the other hand, the electrophilic
additions in water are very fast, yet accompanied by the
nucleophilic attack of the solvent which competes with that
of the anion and formation of bromohydrins is thus observed.
In this respect, the use of ionic liquids may be advantageous
if the medium polarity is able to accelerate the electrophilic
addition process, the nonnucleophilic nature of the medium
avoids the formation of solvent containing byproducts, the
addition reaction occurs with a high or complete stereoselec-
tivity. Ionic liquids, finally, may be recycled if the product-
(s) can be efficiently extracted from the reaction medium.
Here we present results on a practical recycling procedure
for the stereoselective halogen addition to alkenes and
alkynes in several room-temperature ionic liquids.
1
basis of the H and 13C NMR spectra of the crude extracts.
Selected results are reported in Tables 1 and 2.
As shown in Table 1, the reactions of alkenes 1 and 2
and alkynes 5 with Br2 in [bmim][Br] were anti stereospecific
and those of dienes 8, 9, and 13 gave selectively the 1,4
addition products. High anti stereoselectivity was observed
also for bromination of 1c and 2c in [bmim][BF4], although
in this solvent the reaction of diene 13 gave a more complex
reaction mixture (Table 2).
Finally, in [bmim][PF6] only with dialkyl-substituted
alkenes 1a,2a, alkyl substituted alkynes 5a,b, and trans-
stilbenes 2b-d were detected anti-addition products.
Noteworthy, the substituent on the phenyl ring influenced
the stereoselectivity of the reaction of cis isomers 1b-d.
(13) General Procedure for Bromination in Ionic Liquids. To a round-
bottom flask equipped with a magnetic stirrer flea the ionic liquid (2 mL)
and Br2 (96 mg, 0.6 mmol) were added. To the Br2 solution, maintained in
the dark at room temperature, an equimolar amount of the unsaturated
compound was then added under stirring. A water bath was used in order
to avoid the temperature increase during the alkene or alkyne addition.
Products were then extracted at the end of the reaction by three subsequent
addition of Et2O (2 mL), followed by decanting off the ethereal solution of
the products. The combined extracts were concentrated on a rotary
evaporator and the products were analyzed by NMR. When the reactions
were carried out in [bmim][PF6] the uncoloured recovered ionic liquid was
reused.
The addition of Br2 to several alkyl and aryl substituted
alkenes (1 and 2), alkynes (5), and dienes (8, 9, and 13) at
(12) Hardas, N. R.; Adam, R.; Uden, P. C. J. Chromatogr. A 1999, 844,
249.
1062
Org. Lett., Vol. 3, No. 7, 2001

Scheme 2
Table 2. Product Distribution for Br2 Addition to 1, 2, 5, 8, 9,
and 13 in [bmim][PF6] and [bmim][BF4] at Room Temperature
substrate ionic liquid yielda (%)
products
ratiob
1a
1b
1c
1c
1d
2a
2b
2c
2c
2d
5a
5b
5c
5d
5e
8
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][BF4]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][BF4]
95
92
92
92
92
95
92
92
92
92
95
95
95
95
94
95
95
93
95
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
3 + 4
6 + 7
6 + 7
6 + 7
6 + 7
6 + 7
10 + 11
10 + 12
14 + 15 + 16
14 + 15 + 16
>99:1
30:70
70:30
>99:1
>99:1
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
12:88
23:77
25:75
48:52
66:34
42:42:16
47:39:14
1,2-Bromochlorides have been instead obtained by anti
stereospecific and regioselective addition of Cl2 to cis- and
trans-stilbene (1c and 2c) and styrene in [bmim][Br] at room
temperature (Scheme 2).
In this case, the reactions were carried out by addition of
the olefin (0.3 M) under stirring to the ionic liquid containing
an equimolar amount of Cl2, followed byproducts extraction
with Et2O. Gaseous Cl2 was slowly bubbled in the ionic
liquid at low temperature (ca. 0 °C) in order to avoid the
partial decomposition of the solvent.
9
13
13
a Isolated yields. b Determined by H and 13C NMR.
1
In the presence of Br- ions Cl2 should give, in analogy
with the behavior observed in other solvents,16 the BrCl2
-
Dienes 8, 9, and 13 yielded mixtures of 1,2 and 1,4-addition
products. It has been also proved that d,l-dibromides 3b and
3c partially transform into the meso-isomers when the
reactions were carried on in [bmim][PF6].
Comparison of these data with the product distribution
previously found14,15 for Br2 addition to the same compounds
in chlorinated solvents suggests the involvement as electro-
phile of the Br3 species, probably arising by the diffusion
controlled binding of the Br2 by the solvent, when the
reactions are carried out in [bmim][Br]. At variance with
species. The regiochemistry of the addition product to styrene
-
is in agreement with the presence in solution of the BrCl2
anion able to react with the double bonds giving an
electrophilic bromine and a nucleophilic chloride.
Finally, it is noteworthy that in the case of Br2 addition in
[bmim][PF6], after extraction of the products, the ionic liquid
could be recovered and reused for further reactions. The
NMR spectra of the recovered solvent showed no evidence
of liquid degradation thus no appreciable variation in reaction
yields and product stereoselectivity has been observed by
using recovered ionic liquid.
-
-
Br2, no ionic intermediate is involved in the Br3 addition
to double and triple bonds and, at least in chlorinated
solvents, the anti stereospecificity is determined by occur-
rence of a rate- and product-determining nucleophilic attack
by Br- on a 1:1 unsaturated compound-Br2 π-complex.
On the other hand, formation of both syn- and anti-addition
products in the reaction of 1b,c and 5c-e in [bmim][PF6] is
in agreement with the involvement of an ionic intermediate.
The likely electrophile is free Br2. The stereochemical
behavior of these reactions is, however, significantly different
with respect to that observed14,15 in Br2 addition to the same
olefins in chlorinated solvents. In particular, all the reactions
are characterized by a higher anti stereoselectivity, suggesting
a shorter lifetime of the ionic intermediates in the reactions
in ionic liquids.
In conclusion, ionic liquids may be interesting “green”
recyclable alternative solvents for synthesis of dibromo- and
chlorobromo-derivatives. Depending on the ionic liquid the
addition may be stereospecific, erythro- (or meso-)bromo-
chlorides or dibromides are obtained from trans-olefins while
cis-olefins give the corresponding threo- (or d,l-)adducts.
Detailed studies are now under way to investigate the
mechanistic aspects of these reactions.
Acknowledgment. The authors thank Prof. K. R. Seddon
for helpful discussions. Financial support for this research
was provided by Ministero dell’Universita` e della Ricerca
Scientifica (MURST) and Universita` di Pisa.
OL015631S
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Org. Lett., Vol. 3, No. 7, 2001
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