Pentylpyridinium tribromide: A vapor pressure free room temperature ionic liquid analogue of bromine

Article abstract of DOI:10.1055/s-2004-825598

The synthesis and characterization of the room temperature ionic liquid pentylpyridinium tribromide (2) is described. Tribromide 2 was used as a vapor pressure free bromine analogue for the bromination of ketones, aromatics, alkenes, and alkynes. The brominations were carried out in the absence of organic solvents and in most cases the only extraction solvent needed was water. Selectivities and reactivities were shown to be superior to current protocols. The spent reagent pentylpyridinium bromide (1) was easily recycled.

Full text of DOI:10.1055/s-2004-825598

1318
LETTER
Pentylpyridinium Tribromide: A Vapor Pressure Free Room Temperature
Ionic Liquid Analogue of Bromine
P
entylpyri
o
dinium
T
rib
s
Departamento de Química, Universidad Simón Bolívar, Caracas 1080A, Venezuela
Fax +58(212)9063961; E-mail: jsalazar@usb.ve; E-mail: rdorta@usb.ve
Received 26 February 2004
Abstract: The synthesis and characterization of the room tempera-
ture ionic liquid pentylpyridinium tribromide (2) is described. Tri-
bromide 2 was used as a vapor pressure free bromine analogue for
the bromination of ketones, aromatics, alkenes, and alkynes. The
brominations were carried out in the absence of organic solvents
and in most cases the only extraction solvent needed was water. Se-
lectivities and reactivities were shown to be superior to current pro-
tocols. The spent reagent pentylpyridinium bromide (1) was easily
recycled.
Equation 1
sorption at l = 268 nm (e = 1.14 × 104 L mol–1 cm–1). The
conductivity of the neat RTIL 2 was k = 8.09 mS cm–1.
Key words: pentylpyridinium tribromide, room temperature ionic
Excess bromine was likewise readily absorbed by 2. How-
ever, under high vacuum the excess was efficiently re-
moved leaving pure 2. Even after prolonged heating at
70°C under vacuum (<10–2 mmHg), 2 was recovered un-
altered without loss of bromine. The ionic nature of 2 thus
effectively eliminates any noxious residual bromine vapor
pressure.11 RTIL 2 is hydrophobic forming two phases
with water contrasting the highly hydrophilic and hygro-
scopic character of salt 1. Likewise, it forms two phases
with CHCl3, alkanes, aromatic solvents, and ethers. RTIL
2 also showed an extended shelf life of at least 3 months
so far.
liquid, solvent-free brominations
Bromine is widely used for the functionalization of organ-
ic and inorganic substrates. However, bromine is a haz-
ardous chemical that is difficult to manipulate due to its
toxicity and high vapor pressure. Half a century ago, Djer-
assi and Scholz introduced the pyridinium hydrobromide
perbromide (PHP) salt as an alternative, readily weigh-
able, and selective ketone brominating agent.1 PHP
proved also useful for the bromination of alkenes2 and
aromatics,3 as catalyst for aziridinations,4 and for the
stereoselective alkene bromination in water suspension.5
On the other hand, alkylpyridinium salts are well-docu-
mented and commercially available room temperature
ionic liquids (RTIL’s). The combination of an alkylpyri-
dinium cation with the tribromide anion should therefore
lead to a RTIL bromine analogue. Brominations in classic
RTIL media, such as [BMI]PF6, which replace environ-
mentally problematic chlorinated solvents, have been re-
cently demonstrated.6 We disclose here the synthesis, full
characterization, and reactivity of pentylpyridinium tri-
bromide (2), a proton free RTIL bromine analogue that
does not have any measurable vapor pressure. Further-
more, 2 is a rare example of a RTIL which integrates the
function of solvent and reagent.7
RTIL 2 was then tested as brominating agent for a series
of organic substrates and the results are summarized in
Table 1. In general the brominations were performed in
air without solvent and in some cases mechanical stirring
was necessary. Although the reactions were slightly exo-
thermic, no special precautions were taken for cooling.
Reactions giving hydrophobic and water tolerant products
(entries 3 and 5–10) were quenched by adding water. This
caused precipitation of the products as solids or oils,
which were readily separated and washed with fresh por-
tions of water and then dried (either with Na2SO4 or in
vacuo). The aqueous phase containing highly water solu-
ble 1 (and HBr, in the case of monobrominations) was
easily concentrated in vacuo to recycle 1 which then could
be used to regenerate RTIL 2 with bromine (Equation 1).
We emphasize that no organic solvents are needed in
these protocols and that water should only be used to
quench and extract the mixtures at the end of the reac-
tions. The presence of water during the reactions had only
detrimental effects on selectivity and reactivity. On the
other hand, reactions leading to water sensitive or water
miscible products (entries 1, 2 and 4) were extracted with
Et2O.12a
Adding molecular bromine dropwise under mechanical
stirring to powdered pentylpyridinium bromide (1)8 exo-
thermically formed the red liquid pentylpyridinium tribro-
mide (2)9 (Equation 1) which displayed a density of 1.79
g cm–3 and a viscosity of h35–500 = 0.038 Pa s at 25 °C (con-
stant over a shear velocity range between 35 s–1 and 500
s–1).10 The UV–Vis spectrum showed a characteristic ab-
Ketones were cleanly and selectively monobrominated by
2 without the formation of side products (entries 1 and 2).
Ether extraction allowed the separation of the products
SYNLETT 2004, No. 7, pp 1318–1320
Advanced online publication: 10.05.2004
DOI: 10.1055/s-2004-825598; Art ID: S01804ST
© Georg Thieme Verlag Stuttgart · New York
0
3.
0
6.
2
0
0
4

LETTER
Pentylpyridinium Tribromide
1319
Table 1 Solvent-Free Brominations Using Pentylpyridiniumtri-
bromide 2 at Room Temperature
alkynes were selectively dibrominated by 2 in substance.
For example, addition of 2 to cyclohexene led to a bipha-
sic product mixture, which was easily separated.12b Dibro-
mination of phenylacetylene afforded one sole isomer in
excellent yields, while ethylpropiolate led to a cis-trans
mixture in a 94:6 ratio (entries 10, 11). Again, by simple
addition of water at the end of the reactions the products
were separated from 1.
Entry
Substrate
Products
Isolated
yield (%)
1
2
85
92
In summary, an ionic liquid bromine analogue was syn-
thesized and characterized which is safer, easier to use,
and which displayed vastly improved reactivity and selec-
tivity patterns as compared to current bromination tech-
niques. This new functional RTIL 2 may be classified as
‘green’ for the following reasons: (1) it eliminates toxic
bromine vapors, (2) the bromine carrier 1 is readily recy-
cled, and (3) it minimizes the use of organic solvents in
the bromination protocols. Furthermore, 2 was shown in
this preliminary screening to brominate very selectively
and in good to excellent yields a wide variety of substrates
including ketones, aromatics, alkenes, and alkynes.
3
85
4
5
93
90 [a]
6
7
81
90
Acknowledgment
We thank Prof. Henri Arzoumanian (University of Marseille) for
carrying out the elemental analysis of 2 and Prof. Alejandro Müller
(U.S.B.) for viscosity measurements of 2. R. D. thanks FONACIT
(S1-200100871) for financial support. Technical assistance by Ms
Indira Vera of the NMR laboratory at U.S.B. (BID-FONACIT,
Project QF13) is acknowledged.
8
9
84
92
References
10
90
(1) Djerassi, C.; Scholz, C. R. J. Am. Chem. Soc. 1948, 70, 417.
(2) Arcus, C. L.; Strauss, H. E. J. Chem. Soc. 1952, 2669.
(3) (a) Banks, R. E.; Hasszeldine, R. N.; Latham, J. V.; Young,
I. M. J. Chem. Soc. 1965, 594. (b) Reeves, W. P.; Lu, C. V.;
Schulmeier, B.; Jonas, L.; Hatlevik, O. Synth. Commun.
1998, 28, 499.
a Reaction performed in the presence of aq Na2CO3 (1 M).
(4) Ali, S. I.; Nikalje, M. D.; Sudalai, A. Org. Lett. 1999, 1, 705.
(5) (a) Tanaka, K.; Shiraishi, R.; Toda, F. J. Chem. Soc., Perkin
Trans. 1 1999, 3069. Apart from PHP, ammonium
tribromides are widely used brominating agents, see for
example:. (b) Buckles, R. E.; Popov, A. I.; Zelezny, W. F.;
Smith, R. J. J. Am. Chem. Soc. 1951, 73, 4525.
from bromide 1, which after in vacuo treatment was
recycled with one equivalent of bromine to afford 2.
Aromatics13 were brominated by 2 with complete selec-
tivity and in excellent yields: Phenol was cleanly mono-
brominated in the absence of a solvent at room
temperature by 2 within 20 minutes affording exclusively
p-bromophenol (entry 4).12a The simplicity and selectivity
of this phenol bromination protocol compare favorably
with current methods which use solvents and tend to lead
to mixtures of isomers and polybromination. Likewise,
anisole is monobrominated in the presence of one equiva-
lent of 1 M aq Na2CO3 (needed to prevent hydrolysis of
the methoxy function) in excellent isolated yield exclu-
sively in the para position. This reaction was slower than
the phenol bromination (ca. 1.5 h) and the liquid hydro-
phobic product was separated from the aqueous phase
without the need of any extraction solvent. Finally, bromi-
nation of N,N-dimethylaniline (entry 6) afforded p-bro-
mo-N,N-dimethylaniline as the only product in 81%
isolated yield (water was used to quench the reaction and
to precipitate the product as microcrystals). Alkenes and
(c) Avramoff, M.; Weiss, J.; Schaechter, O. J. J. Org. Chem.
1963, 28, 3256. (d) Kajigaeshi, S.; Moriwaki, M.; Tanaka,
T.; Fujisaki, S.; Kakinami, T.; Okamoto, T. J. Chem. Soc.,
Perkin Trans. 1 1990, 897. (e) Muathen, H. A. J. Org.
Chem. 1992, 57, 2740.
(6) Chiappe, C.; Capraro, D.; Conte, V.; Pieraccini, D. Org. Lett.
2001, 3, 1061.
(7) (a) Bates, E. D.; Mayton, R. D.; Ntai, I.; Davis, J. H. Jr. J.
Am. Chem. Soc. 2002, 124, 926. (b) Visser, A. E.;
Swatloski, R. P.; Reichert, W. M.; Mayton, R.; Sheff, S.;
Wierzbicki, A.; Davis, J. H. Jr.; Rogers, R. D. Chem.
Commun. 2001, 135. (c) Bartolini, O.; Bottai, M.; Chiappe,
C.; Conte, V.; Pieraccini, D. Green Chem. 2002, 4, 621.
(8) For a synthesis of 1, see: Zhu, Z.; Ching, C.; Carpenter, K.;
Xu, R.; Selvaratnam, S.; Hosmane, N. S.; Maguire, J. A.
Appl. Organomet. Chem. 2003, 17, 346. Bromide 1 is a
white hygroscopic solid that melts in humid air affording an
‘RTIL’ although, strictly speaking, it is not.
Synlett 2004, No. 7, 1318–1320 © Thieme Stuttgart · New York

1320
J. Salazar, R. Dorta
LETTER
(12) Representative Procedures (a) p-Bromophenol: To
(9) Pentylpyridinium Tribromide (2). Bromine (64.48 g,
404.7 mmol) was added over 30 min to solid crushed
pentylpyridinium bromide (1, 93.07 g, 404.4 mmol) under
mechanical stirring and cooling in a water bath affording a
deep red liquid. After stirring for 2 h the liquid was left in
vacuo overnight. Yield: 156 g (99%); mp 0 °C; k = 8.09 mS
cm–1; d = 1.79 g cm–3; h35–500 0.038 Pa s (all at 25° C). 1H
NMR (CD2Cl2): d = 0.80–1.00 (m, 3 H), 1.30–1.55 (m, 4 H),
2.00–2.15 (m, 2 H), 4.60–4.75 (m, 2 H), 8.10–8.20 (m, 2 H),
8.50–8.65 (m, 1 H), 8.80–8.95 (m, 2 H). 13C NMR (400.14
MHz, CD2Cl2): d = 13.62 (s), 22.12 (s), 28.20 (s), 31.33 (s),
63.14 (s), 129.08 (s), 144.42 (s), 145.86 (s). Anal. Calcd for
C10H16NBr3: C, 30.80; H, 4.14; N, 3.59. Found: C, 30.95; H,
4.11; N, 3.71.
(10) (a) Barnes, H. A.; Hutton, J. F.; Walters, K. An Introduction
to Rheology; Elsevier: Amsterdam, Oxford, New York,
Tokyo, 1989. (b) For the sake of comparison, the viscosities
of bicycle oil and olive oil at r.t. are approximately 10–2 Pa s
and 10–1 Pa s, respectively.
(11) Similar examples that demonstrate the complete elimination
of residual vapor pressure of strong acids in functional RTIL
are: (a) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.;
Weaver, K. J.; Forbes, D. C.; Davis, J. H. Jr. J. Am. Chem.
Soc. 2002, 124, 5962. (b) Susan, M. A. B. H.; Noda, A.;
Mitsushima, S.; Watanabe, M. Chem. Commun. 2003, 938.
crystalline phenol (1.03 g, 10.9 mmol) was added dropwise
2 (4.04 g, 10.3 mmol) over 20 min. The first few drops of 2
caused the phenol crystals to melt and to form a limpid
reaction solution. The resulting orange syrup was left stirring
for another 20 min during which time the color changed to
yellow. Extraction with Et2O (4 × 20 mL) yielded a colorless
oil (1.66 g, 93%) and spectroscopic data corresponded to
pure p-bromophenol. The yellowish ionic liquid phase was
dried under high vacuum, identified as pure 1 (1 is liquid
when moist)8 by 1H NMR (1.99 g, 8.6 mmol), and reacted
with 1 equiv of Br2 to regenerate 2. Note: We do not
recommend the use of recycled 2 from monobrominations
that could contain traces of HBr in acid-sensitive reactions.
(b) 1,2-Dibromocyclohexane: Tribromide 2 (5.00 g, 12.8
mmol) was added dropwise to neat cyclohexene (1.05 g,
12.8 mmol) over 25 min yielding a viscous orange mixture
which was left stirring for 2 h. To the resulting yellow
biphasic system (heavy phase: 1,2-dibromocyclohexane)
was added water (10 mL) for easier phase separation. The
organic product was dried with a small amount of Na2SO4,
filtered and left for 5 min under high vacuum to remove
traces of bromine leaving a colorless liquid (2.60 g, 84%).
Spectroscopic data corresponded to a pure sample of 1,2-
dibromocyclohexane.
(13) For examples, see: (a) Smith, M. B.; Guo, L. C.; Okey, S.;
Stenzel, J.; Yanella, J.; LaChapelle, E. Org. Lett. 2002, 4,
2321. (b) Bora, U.; Bose, G.; Chaudhuri, M. K.; Dhar, S. S.;
Gopinath, R.; Khan, A. T.; Patel, B. K. Org. Lett. 2000, 2,
247.
Synlett 2004, No. 7, 1318–1320 © Thieme Stuttgart · New York