bromide (bmiBr) at room temperature, a transformation of
n-butanol to n-bromobutane occurred almost quantitatively
(entry 5, Table 1). Simple decantation or extraction with
by changing to sulfuric acid, n-chlorobutane reached 35%
conversion in 24 h (entry 2), while methanesulfonic acid gave
a quantitative yield (entry 3). When bmiBr and methane-
sulfonic acid were used, n-bromobutane formed less ef-
ficiently (entry 4) than when H2SO4 was used (entry 5). The
use of bmiI proved to be troublesome, as the reaction gave
rise to a darkened mixture, presumably due to air-oxidation
of iodide (entries 6 and 7). The reactions of n-octanol
followed the same trend (entries 8-12). ses-Butanol and tert-
butanol reacted with various bmiX and acids in the same
fashion as n-butanol (entries 13-17 and 18-23). It should
be pointed out that on the basis of our preliminary results,
H2SO4 is best suited as the acid reactant to produce alkyl
bromides from all three types of alcohols (entries 5, 10, 14,
20), although it seems that tertiary alcohol reacts fastest and
secondary alcohol faster than primary alcohol. Methane-
sulfonic acid appears to be a better choice for the conversion
to alkyl chlorides (entries 3, 9, 19) and alkyl iodides (entries
7, 12, 17, 23).
The mechanism is believed to involve protonation of the
OH group followed by nucleophilic displacement by halide
anions. The proton is presumably in association with either
the halide or the conjugate bases of the Brønsted acids used.
The rate is accelerated largely because of the ionic liquid
media that should aid the charge separation in the transition
state. Although it is too early to conclude that mechanisms
in our reactions will follow the well-established SN2, SN1,
or the so-called borderline scenario5 for the three types of
alkyl alcohols, respectively, the use of ionic liquid reagents/
media does present a challenge to the traditionally perceived
nucleophilic substitution mechanism.6 The ionic liquid reac-
tion media may have a fundamental effect on the reaction
kinetics. The predominantly Coulombic force together with
the lack of extensive solvation (in a traditional sense) in ionic
liquids may exert more important and beneficial influence
on the transition state of carbocation character than in
nonionic liquid media.
Table 1. Conversion of Alcohols to Alkyl Halides Based on
the Reaction in Scheme 1a
entry
R
X
HAb
HCl
time (h)c
yield (%)d,e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-butyl
n-octyl
n-octyl
n-octyl
n-octyl
n-octyl
sec-butyl
sec-butyl
sec-butyl
sec-butyl
sec-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
tert-butyl
Cl
Cl
Cl
Br
Br
I
>48
24
24
N.R.f
35
98
H2SO4
CH3SO3H
CH3SO3H
H2SO4
H2SO4
CH3SO3H
H2SO4
CH3SO3H
H2SO4
H2SO4
CH3SO3H
CH3SO3H
H2SO4
CH3SO3H
H2SO4
CH3SO3H
HCl
CH3SO3H
H2SO4
CH3SO3H
H2SO4
CH3SO3H
24
57
20 (3)
24 (5)
5
19
24
5.5
22
24
24
12 (3)
24
24
24
>48
24
1
24
24
30
95 (83)
30 (10)
50
I
Cl
Cl
Br
I
50
100
98 (90e)
30
70
25
95 (86)
15
80
75
N.R.
25
I
Cl
Br
Br
I
I
Cl
Cl
Br
Br
I
95
15
35
95
I
a Notes: All reactions were conducted at room temperature in capped
vials at 2 mmol scale using 1 equiv of ionic liquids, 1 equiv of alcohols,
and 1 equiv of acids. b HCl (37% aqueous), H2SO4 (95% aqueous), and
neat CH3SO3H were used. c Numbers in parentheses represent repeated
experiments. d Yields are based on GC/MS. e Isolated yield. f N. R. ) no
reaction.
hexanes was sufficient to achieve the separation of n-
bromobutane, without further purification. The 1-n-butyl-3-
methylimidazolium cation was recycled in the form of an
ionic liquid (presumably bmiHSO4).
This transformation is significant from the viewpoint of
pollution avoidance. A widely used method of converting
n-butanol to n-bromobutane involves the heating under reflux
of n-butanol and sodium bromide (NaBr) in a large excess
of concentrated H2SO4. The n-bromobutane product is then
removed azeotropically together with water and unreacted
n-butanol from the reaction mixture, followed by washing
with concentrated H2SO4.4
We then investigated several classes of alcohol substrates
in halide-based ionic liquids using other Brønsted acids. The
results are summarized in Table 1. For reason unknown,
n-butanol and tert-butanol failed to react with bmiCl when
HCl was employed (entries 1 and 18, respectively). However,
In conclusion, we have demonstrated that the conversion
of alkyl alcohols can be efficiently accomplished using 1,3-
dialkylimidazolium halide-based ionic liquids and Brønsted
acids at room temperature under mild conditions. Further
studies on the detailed reaction mechanisms are underway.
Acknowledgment. The authors thank Wesleyan Univer-
sity for a start-up fund.
Supporting Information Available: General experimen-
tal procedure for conversion of alcohols to alkyl halides and
spectra data for isolated 1-bromooctane. This material is
available free of charge via the Internet at http:/pubs.acs.org.
OL016672R
(3) Although bmiCl and bmiBr are solids at room temperature, warming
up or addition of cosolvents such as water can render them liquidlike due
to their hydrophilicity.
(4) Nohrig, J. R.; Hammond, C. N.; Morrill, T. C.; Neckers, D. C.
Experimental Organic Chemistry; W. H. Freeman and Company: New
York, 1998; p 369.
(5) Carey, F. A.; Sundberg, R. J. AdVanced Organic Chemistry, Part A:
Structure and Mechanisms, 4th ed.; Kluwer Academic/Plenum Publishers:
New York, 2000; Chapter 5.
(6) A report on ionic liquids as catalytic green solvents for nucleophilic
displacement has just appeared. See: Wheeler, C.; West, K. N.; Liotta, C.
L.; Eckert, C. A. Chem. Commun. 2001, 887.
3728
Org. Lett., Vol. 3, No. 23, 2001