Biodegradable pyridinium ionic liquids: Design, synthesis and evaluation

Article abstract of DOI:10.1039/b811814k

A range of ionic liquids (ILs) with a pyridinium cation were synthesised and their biodegradability was evaluated using the CO₂ Headspace test (ISO 14593). ILs bearing an ester side chain moiety were prepared from either pyridine or nicotinic acid and showed high levels of biodegradation under aerobic conditions and can be classified as 'readily biodegradable'. In contrast, pyridinium ILs with alkyl side chains showed significantly lower levels of biodegradability in the same test. The utility of the biodegradable IL 6c as a reaction solvent for the Diels-Alder reaction was also investigated.

Full text of DOI:10.1039/b811814k

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www.rsc.org/greenchem | Green Chemistry
Biodegradable pyridinium ionic liquids: design, synthesis and evaluation
Jitendra R. Harjani,a Robert D. Singer,b M. Teresa Garciac and Peter J. Scammells*a
Received 10th July 2008, Accepted 30th September 2008
First published as an Advance Article on the web 7th November 2008
DOI: 10.1039/b811814k
A range of ionic liquids (ILs) with a pyridinium cation were synthesised and their biodegradability
was evaluated using the CO2 Headspace test (ISO 14593). ILs bearing an ester side chain moiety
were prepared from either pyridine or nicotinic acid and showed high levels of biodegradation
under aerobic conditions and can be classified as ‘readily biodegradable’. In contrast, pyridinium
ILs with alkyl side chains showed significantly lower levels of biodegradability in the same test.
The utility of the biodegradable IL 6c as a reaction solvent for the Diels–Alder reaction was also
investigated.
would address both of these issues. As ILs make a transition
Introduction
from academic curiosities to commercial commodities, their
Ionic liquids (ILs) have earned themselves a reputation as
environmental impact is certainly concerning.9 Rightfully so,
excellent reaction media. Earlier applications of ILs were mainly
the life cycle assessment of newer chemicals (such as ILs) and
as electrolytes, solvents and extractants. The scope of their
designing benign chemicals are now considered as an integral
application is now broader and covers their use as reaction
part of green chemistry.10
media, fuel cells, optical fluids, solar cells, energetic materials,
In contrast to the other possible fates of any chemical released
heat transfer fluids and lubricants, to name only a few.1 In
into the environment, biodegradation appears to be the cleanest
chemical synthesis, the initial interest in the use of ILs was
ultimate fate for any compound. This natural process of decay
mainly to realize their advantages for transition metal mediated
is an intensive collective endeavor of a number of microbes with
catalysis in biphasic reaction systems.2 With time, this was
different metabolic capabilities, ultimately leading to the forma-
further broadened by utilising them for catalysis using supported
tion of non-toxic inorganic products such as carbon dioxide,
IL phases,3 designing task-specific (functionalized) ILs for
water and/or biomass. The assessment of environmental impact
catalysis,4 using ILs as supports for the substrates5 and designing
of ILs has mainly centered on the evaluation of their toxicity,10b,11
novel materials.6 The properties of ILs, such as broad solvating
however it is known that a refractory organic substance, if
ability, good thermal and chemical stability, non-volatility and
released in to the environment, would bio-accumulate and may
non-flammability under operational conditions, not only adds
eventually lead to chronic toxic effects.12 Earlier investigations
to their versatility, but may make them a safer substitute to
have also indicated that structural features, such as alkyl chain
conventional solvents. ILs as reaction media can offer better
length, that can decrease resistance to microbial attack may also
reaction selectivity, higher reaction yields and reusability. These
increase the toxicity of the ILs.13 As suitable structural design
advantages further add to their green attributes. Although, some
of these properties, such as good chemical stability, volatility
has helped integrate low toxicity with high biodegradability in
some commercial products in the past (e.g. drilling fluids), we
believe that appropriately designing the ILs may lead to the
solvents with desired attributes that would not pose problems to
etc., have been challenged, it is notable that not all the ILs have
all these ideal properties.7 By varying the cations and anions
that constitute their structure, it is typically possible to design
the environment.12
ILs with the desired solvent characteristics for the chemical
Our initial investigations on the evaluation of biodegradability
process of interest. The only principles of green chemistry
of ILs were centered on the most commonly used imidazolium
which may disqualify ILs as a green solvent replacements are
based ILs. The biodegradability of this class of ILs increased
the necessity to ‘use safer solvents and reaction conditions’
if the ester group was integrated in to the structure, however
and ‘design chemicals and products to degrade after use’.8
the amide group did not have any significant influence.14 The
Designing ILs that are safe to release in to the environment
ester group derived from a C2 acid and C5 linear alcohol on
the imidazolium side chain and the octyl sulfate anion together
enhances the ready biodegradability of the IL to meet the
aMedicinal Chemistry and Drug Action, Monash Institute of
standard 60% cutoff value in 28 days.15
Pharmaceutical Sciences, Monash University, Parkville, 3052, Victoria,
Our interest in assessing the biodegradability of the pyri-
dinium based ILs (another commonly used class of ILs) was due
to their popularity as ionic solvents. Our curiosity was peaked by
the results reported by Engberts and Hulst et al.16 Their research
on the pyridinium based amphiphiles showed high vulnerability
of their products to enzymatic attack. Their results were also
Australia. E-mail: peter.scammells@vcp.monash.edu.au;
Fax: +61 3 99039582; Tel: +61 3 9903 9542
bDepartment of Chemistry, Saint Mary’s University, Halifax,
Nova Scotia, B3H 3C3, Canada
cDepartment of Surfactant Technology, IIQAB-CSIC, Jordi Girona
18–26, 08034, Spain. E-mail: mtgbet@iiqab.csic.es; Fax: +34 93 204
5904; Tel: +34 93 400 6100
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suggestive of very low toxicity of these compounds. Around
the same time, the results on the study of biodegradability
of some cationic surface active compounds with pyridinium
head group also indicated the susceptibility of the pyridinium
ring towards the microbial attack.17 While our studies were
underway, Docherty et al. measured biodegradability of 1,3-
dialkylpyridinium bromides using the OECD 301 A (DOC Die-
Away Test), and found that pyridinium bromide with a linear C6
side chain mineralized completely after 49 days of incubation,
and with a linear C8 side chain, mineralization occurred after
25 days.18 1H NMR, DNA-PCR-DGGE and TDN analysis es-
tablished that the pyridinium ring is metabolized in the process of
biodegradation. Very recently, Jastorff et al. investigated a family
of unsubstituted and substituted 1-n-alkylpyridinium halides
for biodegradation.19 The disappearance of the substrates was
monitored by HPLC (with UV detection) to calculate their
primary biodegradation. However, as respirometric parameters
(O2 depletion/CO2 formation) were not used for the measure-
ment of mineralization, the method does not reflect the ready
biodegradability of the compounds tested. Being interested by
these reports, we sought to systematically investigate the ready
biodegradability of the pyridinium based ILs/salts derived from
pyridine and nicotinic acid, a relatively inexpensive natural
product that can be used to incorporate the pyridinium core
in the IL moiety.20
Results and discussion
Target ionic liquids were prepared using standard methodology.
This initially involved alkylation of pyridine or the appropriate
3-substituted pyridine with an alkyl halide to afford the cor-
responding pyridinium halide (Scheme 1). Alternative anions
were subsequently introduced by a metathesis reaction with
sodium octyl sulfate, potassium hexafluorophosphate or lithium
bis(trifluormethanesulfonimide).
Fig. 1 Percentage biodegradability of the alkyl pyridinium based
quaternary salts 1a (᭺), 1b (ꢀ), 1c (+), 1d (ꢀ), 2a (¥), 2b (♦), 3 (ꢁ) and
4 (ꢂ).
The introduction of the ester group seems to have a profound
effect on the biodegradability of these salts.21 The quaternary
salt 5a derived from two simple starting materials, pyridine
and ethyl bromoacetate and the corresponding octyl sulfate
IL, 5b, both showed a comparable biodegradability at 87 and
89% respectively (Fig. 2). The biodegradability attained by these
compounds after the first 7 days was 71 and 74% respectively
(Fig. 2). As the halide ionis not likely tohave significant influence
on biodegradability, these results indicate that the pyridinium
nucleus is not refractory and that appropriate structural manip-
ulations of this core can lead to compounds with good ready
biodegradability values. It is also worth noting that the presence
or absence of the octyl sulfate anion (which is generally known to
have positive influence on the ready biodegradability) seems to
have only a meagre influence on the overall high biodegradability
Scheme 1 Synthesis of pyridinium ILs.
Pyridinium salts with C4 linear alkyl chains at position 1
(compounds 1a, c and d) did not show high levels of biodegra-
dability (Fig. 1). The presence of the methyl group at the 3-
position of the pyridine ring helps induce the asymmetry in
the structure, rendering the salt 2a liquid at room temperature,
but certainly does not help improve the biodegradability of the
-
-
IL. The 1-butylpyridinium salts based on Br-, PF6 and NTf2
showed only 1–3% biodegradability over a 28 day period, unless
octyl sulfate was employed as the anion. The biodegradability
as high as 37–40% was attained by the incorporation of an
octyl sulfate counter ion, which is obviously an effect induced
by the anion. These observations on the resistance of 1-
butylpyridinium salts towards biodegradation are consistent
with the earlier results documented by Docherty18 and Jastorff
et al.19 1-Alkylpyridinium bromides with linear C10 and C16
substituents (3 and 4) showed poor biodegradability at 9% and
0%, respectively.
-
values. The exchange of bromide ion with NTf2 produces a
-
low viscosity IL 5c and with PF6 produces a solid 5d which is
sparingly solubility in water. Both 5c and 5d contain fluorine in
the anion component and show ready biodegradability at 64 and
86% respectively, both above the 60% threshold (Fig. 2). It is also
-
notable that in this series the NTf2 based IL offers lower (by
23% on average) biodegradability than the corresponding Br-,
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Fig. 2 Percentage biodegradability of alkyl pyridinium based quater-
nary salts with ester group appended on the side chain; 5a (¥), 5b (+),
5c (ꢀ) and 5d (ꢀ).
OctOSO3- and PF6- counterparts. This may, in part, be because
of the lack of water miscibility of the NTf2- based IL. The good
biodegradability of ILs with fluorine containing anions such as
NTf2 and PF6 is particularly significant as the ILs with these
anions possess good solvent characteristics and these anions are
amongst the most commonly encountered in ILs.
Fig. 3 Percentage biodegradability of alkyl pyridinium based quater-
-
-
nary salts derived from nicotinic acid; 6a (ꢀ), 6b (¥), 6c (ꢂ), 6d (+), 7b
(ꢁ) and 8b (᭺).
ILs derived from nicotinic acid in which the ester moi-
ety was incorporated into the 3-position of the pyridinium
cation were also investigated. Synthesizing the ILs from bio-
renewable chemicals such as nicotinic acid, as opposed to
petrochemicals such as pyridine is acknowledged as a good
argument in favor of sustainable development of products.22
Butyl nicotinate was synthesized from nicotinic acid and was
subjected to quaternization with alkyl iodides, mainly because
of the reduced nucleophilicity of the nitrogen on the pyridine
ring. The quaternization of butyl nicotinate with methyl iodide
produced 6a. The N-alkylation of butyl nicotinate with butyl
iodide followed by anion metathesis yields 7b. Both 6a and 7b
offer promising biodegradability at 72 and 84%, respectively
(Fig. 3). The octyl sulfate containing 6b, the triflimide based 6c
and the hexafluorophosphate containing IL 6d were synthesized
from quaternary iodide 6a showed biodegradability at 75, 68
and 75% respectively (Fig. 3). It is notable that 6a–d showed
greater than 60% biodegradability within the first seven days
of incubation. The increased biodegradability of 7b over 6b is
perhaps because of an increase in the lipophilicity of cation. This
finding is consistent with previous studies in which cations with
longer alkyl side chains were found to be more biodegradable.14,19
The simple primary amide N-butyl nicotinamide derived from
nicotinic acid and butyl amine was used to synthesize the
nicotinamide based IL 8b. The ready biodegradability of 30%
(Fig. 3) after a standard 28 day period perhaps indicates the
recalcitrance of the nicotinamide derived IL under the test
conditions. This inertness of amide containing IL is consistent
with our earlier observations on the imidazolium series under
similar test conditions.14 The resistance of amides towards
biodegradation has also been documented earlier in the design
of biodegradable imidazolium ILs.12
Compounds which undergo 60% mineralization in 28 days
using methods based on respirometry are defined as “readily
biodegradable”. Levels of 60% mineralization also may indicate
the use of test substances for the production of biomass (which
is eventually but not immediately used as a source of energy)
and thus this value may equate to higher levels of ultimate
biodegradation (around 90%) and even higher values of primary
biodegradation (at least > 90%). It is important to note that the
tests for ready biodegradability are generally performed under
the most stringent conditions of lower microbial population and
with the test substance as the sole source of carbon. Also, the
concentration of the test substance is unrealistically higher than
what would normally be observed in a practical scenario in the
environment or a typical waste water treatment plant. Therefore
60% biodegradability obtained by these methods indicates
that the test substance should undergo speedy and complete
biodegradation upon release into an aquatic environment. Not
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surprisingly, the tests for ready biodegradability have had a long
history of successful applications.
ketone (Entry 2), dimethylacetylene dicarboxylate (Entry 3),
maleic anhydride (Entry 4), N-phenylmaleimide (Entry 5) and
dimethyl maleate (Entry 6) were also investigated. In all cases,
the dienophiles reacted readily with cyclopentadiene in the BIL
6c to produce the corresponding Diels–Alder adduct in good
to nearly quantitative yields. It is notable that the reactivity is
dictated by the electron deficient character of the dienophile,
which also indirectly influences the reaction time and selectivity.
The reactive dienophiles also offer excellent endo selectivity.
The crude products in all the cases were isolated by extracting
the reaction mixture with diethyl ether. The purity of IL was
A preliminary investigation into the use of the biodegrad-
able ionic liquid (BIL), 3-(butoxycarbonyl)-1-methylpyridinium
triflimide (6c), as a reaction solvent has also been conducted.
We chose the Diels–Alder reaction for this purpose as this
cycloaddition is one of the most extensively used methods to
construct six membered carbo- and heterocyclic compounds.23
This reaction has been investigated well not only in the Lewis
acidic ILs,24 but also in the ‘second generation’ neutral ILs.25 In
the neutral ILs the rates of this reaction are increased by doping
the IL with Lewis acid catalysts26 or mineral acid catalysts.27 The
combination of neutral ILs with ultrasound28 or microwave29
has also proved useful in enhancing the rate of this reaction. It
has been demonstrated that ILs not only offers an advantage
as a reaction media, but also exert effects on the rates30 and
selectivity31 of Diels–Alder reaction when compared with the
conventional solvents. The reaction has also been investigated
in the imidazolium based BILs by our group.32 Accordingly, the
plethora of comparative data available for Diels–Alder reactions
in covalent solvents and ionic liquids made it an obvious choice
for the evaluation of the novel ionic liquids reported herein.
Cyclopentadiene was used as the diene component, as it is
one of the most commonly used reactive diene in Diels–Alder
reactions. The reaction of cyclopentadiene with methyl acrylate
afforded 70% product after 24 h and 97% after 72 h (Table 1,
Entry 1). A range of other dienophiles, including methyl vinyl
1
ascertained by H NMR and can be reused after evaporating
the traces of diethyl ether under reduced pressure. The products
in all the cases were purified by column chromatography and the
endo:exo ratio in all the cases was determined by 1H NMR.
Conclusions
It can be concluded that ionic liquids with a pyridinium cation
bearing an ester containing substituent at positions 1 or 3 show
excellent biodegradability. The biodegradability does not seem
to significantly depend on the anion, although some effects
are apparent. The high ready biodegradability values attest the
earlier claims of tendency of the pyridine ring to mineralize.16–19
In contrast, 1-alkylpyridinium ILs with linear C4, C10 and
C16 showed relatively low levels of biodegradability. Although
the presence of linear alkyl chains is an important factor in
designing biodegradable compounds as they can act as potential
sites for attack by oxygenases,10b,14b no significant improvement
was detected for these 1-alkylpyridinium bromides. However, as
ionic liquids with longer alkyl chains have been proven to be
more toxic,15b,33 further studies are underway to clarify if their
resistance towards biodegradation in the ready biodegradability
tests could be related to their toxic effects on the biological
activity of the aerobic micro-organisms.
Table 1 Diels–Alder reactions in 3-(butoxycarbonyl)-1-methyl-
pyridinium triflimide (6c)
Reaction
time
Entry Dienophile
1
Isolated yielda endo:exo ratiob
72 h
97%
57%
97%
76:24
79:21
100:0
The biodegradable ionic liquid (BIL), 3-(butoxycarbonyl)-
1-methylpyridinium triflimide (6c), was demonstrated to be a
viable reaction medium as exemplified with the Diels–Alder
reaction. In general, high yields and endo selectivities were
observed.
2
3
72 h
2 h
Experimental
4
5
6
10 min
10 min
18 h
100%
97%
95%
100:0
100:0
95:5
Synthesis
Nicotinic acid (Sigma-Aldrich, 98%), lithium triflimide
(Aldrich, 97%), potassium hexafluorophosphate (Fluka, 98%),
sodium octyl sulfate (Sigma, ~95%), methyl iodide (Sigma-
Aldrich, 99%), butyl iodide (Fluka ≥ 98%), 1-butanol (BDH,
99%), thionyl chloride (Fluka, ≥ 99%), ethyl bromoacetate
(Merck, > 98%), toluene (Merck, GR, ≤ 0.03% H2O), acetoni-
trile (Merck, Chromatography grade, ≤ 0.02% H2O), diethyl
ether (Merck, GR, ≤ 0.03% H2O), butyl amine (Sigma-Aldrich,
99.5%), pyridine (BDH, 98%) and triethylamine (Sigma-
Aldrich, 99%) were procured from the commercial supplier and
used without any pre-treatment. The 1H and 13C NMR spectra
of the purified products were recorded in CDCl3 (Cambridge
Isotope Laboratories Inc., 99.8% D) or DMSO d6 (Cambridge
Isotope Laboratories Inc., 99.9% D) on a Bruker Avance
a Isolated by column chromatography. b Determined by 1H NMR.
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DPX 300 spectrometer at 300 and 75.4 MHz, respectively. Low
resolution mass spectra using electrospray ionisation (ES-MS)
were obtained using a Micromass Platform II instrument. Unless
otherwise stated, cone voltage was 20 eV.
layer or solid from the initially obtained clear and homogenous
mixture of amine and alkyl halide in toluene. The product was
isolated by decanting the toluene layer to remove the unreacted
starting materials and solvent. Subsequently, the quaternary salt
was washed with diethyl ether (4 ¥ 20 mL) and each time the ether
layer was separated from the quaternary halide by decantation.
In some cases, the ether washings resulted in the formation of a
solid. The solid was purified by dissolving in acetonitrile (20 mL)
and precipitation with diethyl ether (60–70 mL). In each case,
the IL/salt was finally dried at a reduced pressure to get rid
of all the volatile organic compounds. These quaternary salts
(except 6a) being hygroscopic, were handled under nitrogen at
each stage of synthesis and purification.
Butyl nicotinate
Thionyl chloride (81.30 mmol) was gradually added to the
suspension of nicotinic acid (40.65 mmol) in toluene (100 mL)
maintained at room temperature. The reaction mixture was
heated at 100 ◦C for 24 h, to assure the quantitative formation
of the nicotinic acid chloride (as a hydrochloride salt). After
decanting the solution of unreacted thionyl chloride in toluene,
the acid chloride was washed with diethyl ether (4 ¥ 50 mL)
and then treated with dichloromethane (100 mL). The reaction
mixture was cooled under dry ice and gradually treated with
triethylamine (81.30 mmol) followed by 1-butanol (81.30 mmol).
The reaction mixture was stirred at room temperature for 24 h
and then treated with water and stirred vigorously to yield a clear
dichloromethane layer. Butyl nicotinate, being a water insoluble
Brønsted base, was separated and purified by treating the organic
layer with 6 N HCl solution (20 mL). The acidic aqueous
layer was first extracted with dichloromethane (2 ¥ 20 mL),
and treated with an aqueous base, ammonium hydroxide, to
release the pure ester. The ester was separated by extraction of
the aqueous layer with dichloromethane (2 ¥ 20 mL), followed
1-Butylpyridinium bromide (1a). Yield 96%. 1H NMR
(CDCl3): d 0.89–0.94 (t, J = 7.4 Hz, 3H), 1.33–1.43 (m, 2H),
1.96–2.06 (m, 2H), 4.96–5.01 (t, J = 7.5 Hz, 2H), 8.11–8.16 (m,
2H), 8.50–8.56 (m, 1H), 9.59–9.62 (m, 2H). 13C NMR (CDCl3):
d 13.4, 19.1, 33.7, 61.5, 128.4, 145.2. ES-MS (+ ve): m/z, 136.3
[M–Br-]+; ES-MS (-ve): m/z, 79.1 and 81.1 [Br]-.
1-Butyl-3-methylpyridinium bromide (2a). Yield 96%. 1H
NMR (CDCl3): d 0.94–0.99 (t, J = 7.4 Hz, 3H), 1.37–1.49 (m,
2H), 1.99–2.09 (m, 2H), 2.66 (s, 3H), 4.95–5.00 (t, J = 7.5 Hz,
2H), 7.98–8.03 (m, 1H), 8.24–8.27 (m, 1H), 9.31–9.33 (m, 1H),
9.46 (s, 1H). 13C NMR (CDCl3): d 13.5, 18.6, 19.3, 33.8, 61.4,
127.8, 139.6, 142.4, 144.7, 145.6. ES-MS (+ ve): m/z, 150.1 [M–
Br-]+; ES-MS (-ve): m/z, 78.9 and 80.8 [Br]-.
1
by drying and evaporation at reduced pressure. Yield 50%. H
NMR (CDCl3): d 0.97–1.02 (t, J = 7.4 Hz, 3H), 1.43–1.55 (m,
2H), 1.73–1.83 (m, 2H), 4.36–4.40 (t, J = 6.6 Hz, 2H), 7.40–7.44
(m, 1H), 8.31–8.35 (m, 1H), 8.77–8.79 (m, 1H), 9.23–9.24 (m,
1H). 13C NMR (CDCl3): d 13.8, 19.3, 30.8, 65.4, 123.4, 126.5,
137.1, 151.0, 153.4, 165.4. ES-MS (+ ve): m/z, 180.0 [M + 1]+.
1-Decylpyridinium bromide (3). Yield 96%. 1H NMR
(DMSO d6): d 0.81–0.85 (t, J = 5.6 Hz, 3H), 1.22–1.26 (m,
14H), 1.89–1.93 (m, 2H), 4.64–4.69 (t, J = 6.8 Hz, 2H), 8.16–
8.20 (m, 2H), 8.61–8.66 (m, 1H), 9.21–9.23 (m, 2H). 13C NMR
(DMSO d6): d 13.7, 21.9, 25.2, 28.3, 28.5, 28.6, 28.7, 30.7, 31.1,
60.4, 127.9, 144.7, 145.4. ES-MS (+ ve): m/z, 220.2 [M–Br-]+;
ES-MS (-ve): m/z, 79.0 and 81.0 [Br]-.
N-Butyl nicotinamide
The acid chloride was prepared and purified as per the procedure
described above. The reaction mixture was cooled under dry
ice and gradually treated with butyl amine (122 mmol). After
stirring at room temperature for 3 h, the reaction mixture
was treated with water and stirred vigorously to yield a clear
dichloromethane layer. The isolation of product was carried out
by quenching the reaction mixture with water, followed by drying
and evaporation of the dichloromethane at reduced pressure.
Yield 52%. 1H NMR (CDCl3): d 0.96–1.01 (t, J = 7.2 Hz, 3H),
1.38–1.50 (m, 2H), 1.59–1.69 (m, 2H), 3.46–3.53 (m, 2H), 6.15
(bs, 1H), 7.37–7.41 (m, 1H), 8.10–8.14 (m, 1H), 8.72–8.74 (m,
1H), 8.95–8.96 (m, 1H). 13C NMR (CDCl3): d 13.8, 20.2, 31.6,
40.0, 123.4, 130.7, 135.1, 148.2, 151.9, 165.9. ES-MS (+ ve): m/z,
179.0 [M + 1]+.
1
1-Hexadecylpyridinium bromide (4). Yield 92%. H NMR
(DMSO d6): d 0.80–0.85 (t, J = 6.6 Hz, 3H), 1.21–1.26 (m,
26H), 1.89–1.93 (m, 2H), 4.65–4.70 (t, J = 7.5 Hz, 2H), 8.16–
8.21 (m, 2H), 8.61–8.66 (m, 1H), 9.23–9.24 (m, 2H). 13C NMR
(DMSO d6): d 13.8, 22.0, 25.3, 28.3, 28.6, 28.7, 28.8, 28.9, 29.0,
30.7, 31.2, 60.5, 128.0, 144.7, 145.40. ES-MS (+ ve): m/z, 304.4
[M–Br-]+; ES-MS (-ve): m/z, 79.0 and 81.0 [Br]-.
1-(2-Ethoxycarbonyl)methylpyridinium bromide (5a). Yield
1
89%. H NMR (DMSO d6): d 1.24–1.29 (t, J = 7.2 Hz, 3H),
4.21–4.28 (q, J = 7.1 Hz, 2H), 5.68 (s, 2H), 8.23–8.27 (m, 2H),
8.70–8.75 (m, 1H), 9.05–9.07 (m, 2H). 13C NMR (DMSO d6): d
13.9, 60.2, 62.2, 127.7, 146.2, 146.7, 166.3. ES-MS (+ ve): m/z,
166.1 [M - Br-]+; ES-MS (-ve): m/z, 79 and 81 [Br-].
General procedures for the synthesis of pyridinium halides (1a,
2a, 3, 4, 5a and 6a)34
3-(Butoxycarbonyl)-1-methylpyridinium iodide (6a). Yield
1
98%. H NMR (DMSO d6): d 0.92–0.97 (t, J = 7.4 Hz, 3H),
1.39–1.52 (m, 2H), 1.70–1.79 (m, 2H), 4.39–4.45 (m, 5H), 8.24–
8.29 (m, 1H), 8.95–8.98 (m, 1H), 9.19–9.21 (m, 1H), 9.52 (s,
1H). 13C NMR (DMSO d6): d 13.4, 18.4, 29.9, 48.4, 66.0, 127.8,
129.2, 144.6, 146.5, 148.7, 161.6. ES-MS (+ ve): m/z 194.0 (M–
I-)+; ES-MS (-ve, 70 eV): m/z, 126.8 [I]-.
To the solution of pyridine/3-substituted pyridine (33.3 mmol)
in toluene (20 mL), was added alkyl halide (40.0 mmol) at room
temperature, followed by stirring at room temperature for 1 h
under nitrogen. The reaction mixture was then stirred at 110 ◦C
for 24 h. In the case of 5a and 6a, the reactions were heated at
70 ◦C and 45 ◦C, respectively. In all the cases, the completion of
the reaction was marked by the separation of either the dense IL
3-(Butoxycarbonyl)-1-butylpyridinium iodide (7a). Butyl
nicotinate (33.3 mmol) was treated with butyl iodide
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(166.5 mmol) at room temperature and the reaction mixture
was heated at 140 ◦C for 48 h, while been stirred under nitrogen
atmosphere. The resultant reaction mixture was treated with
water (40 mL) and stirred for 10 min. The aqueous quaternary
iodide solution was purified by extracting it with diethyl ether
(3 ¥ 20 mL). A light yellowish brown liquid was obtained by
freeze drying the purified aqueous solution and further drying
for 24 h at 50 ◦C under reduced pressure. Yield 70%. 1H NMR
(DMSO d6): d 0.90–0.97 (m, 6H), 1.29–1.50 (m, 4H), 1.70–1.77
(m, 2H), 1.89–1.94 (m, 2H), 4.39–4.43 (t, J = 6.5 Hz, 2H), 4.69–
4.74 (t, J = 7.5 Hz, 2H), 8.26–8.31 (m, 1H), 8.97–9.00 (m, 1H),
9.28–9.30 (m, 1H), 9.59 (s, 1H). 13C NMR (DMSO d6): d 13.3,
13.5, 18.5, 18.7, 30.0, 32.7, 60.9, 66.1, 128.3, 130.0, 145.0, 145.8,
147.8, 161.7. ES-MS (+ ve): m/z 236.3 (M–I-)+; ES-MS (-ve,
70 eV): m/z, 126.9 [I]-.
(t, J = 7.5 Hz, 2H), 7.93–7.97 (m, 1H), 8.19–8.22 (m, 1H), 8.94–
8.96 (m, 1H), 9.02 (s, 1H). 13C NMR (CDCl3): d 13.6, 14.2, 18.7,
19.4, 22.7, 26.0, 29.3, 29.4, 29.7, 31.9, 33.8, 61.8, 67.7, 128.0,
139.9, 142.6, 145.0, 145.5. ES-MS (+ ve): m/z, 150.1 [M–Br-]+;
ES-MS (-ve): m/z, 209.1 [C8H17OSO3]-.
1-(2-Ethoxycarbonyl)methylpyridinium octyl sulfate (5b).
1
Yield 83%. H NMR (DMSO d6): d 0.84–0.88 (t, J = 5.7 Hz,
3H), 1.25–1.29 (m, 12H), 1.45–1.47 (m, 2H), 3.65–3.69 (t, J =
6.8 Hz, 3H), 4.21–4.28 (q, J = 7.1 Hz, 2H), 5.65 (s, 2H), 8.22–
8.27 (m, 2H), 8.69–8.74 (m, 1H), 9.02–9.05 (m, 2H). 13C NMR
(DMSO d6): d 13.9, 22.0, 25.5, 28.6, 28.7, 29.0, 31.2, 60.3, 62.3,
65.4, 127.8, 146.3, 146.7, 166.3. ES-MS (+ ve): m/z, 166.1 [M -
C8H17OSO3 ]+; ES-MS (-ve): m/z, 209.1 [C8H17OSO3]-.
-
3-(Butoxycarbonyl)-1-methylpyridinium octyl sulfate (6b).
1
1-Butyl-(3-butylcarbamoyl)pyridinium iodide (8a). Butyl io-
dide (30.64 g, 166.5 mmol) was added to the solution of N-
butylnicotinamide (5.933 g, 33.3 mmol) in toluene (20 mL)
under nitrogen atmosphere. The reaction mixture was heated at
110 ◦C for 48 h, while maintaining the inert atmosphere. Toluene
was evaporated at a reduced pressure and the resultant product
was treated with water (50 mL). The crude aqueous quaternary
iodide solution was extracted with diethyl ether (4 ¥ 20 mL).
A light yellow liquid was obtained by freeze drying the purified
aqueous solution and subsequent drying under reduced pressure
for 24 h at 50 ◦C. Yield 74%. 1H NMR (CDCl3): d 0.93–1.03 (m,
6H), 1.37–1.51 (m, 4H), 1.71–1.79 (m, 2H), 2.02–2.12 (m, 2H),
3.46–3.53 (m, 2H), 4.89–4.94 (t, J = 7.5 Hz, 2H), 8.09–8.14 (m,
1H), 8.66–8.69 (m, 1H), 9.11–9.16 (m, 2H), 10.05 (s, 1H). 13C
NMR (CDCl3): d 13.5, 13.8, 19.4, 20.3, 31.2, 33.5, 40.3, 62.1,
128.4, 134.9, 143.6, 145.1, 145.9, 160.8. ES-MS (+ ve): m/z 235.3
(M–I-)+; ES-MS (-ve, 70 eV): m/z, 126.9 [I]-.
Quantitative. H NMR (CDCl3): d 0.85–0.90 (t, J = 6.5 Hz,
3H), 0.97–1.02 (t, J = 7.4 Hz, 3H), 1.26–1.35 (m, 10H), 1.42–
1.66 (m, 4H), 1.76–1.86 (m, 2H), 3.91–3.96 (t, J = 6.9 Hz, 2H),
4.43–4.48 (t, J = 6.8 Hz, 2H), 4.72 (s, 3H), 8.24–8.29 (m, 1H),
8.88–8.91 (m, 1H), 9.26 (s, 1H), 9.59–9.61 (m, 1H). 13C NMR
(CDCl3): d 13.8, 14.2, 19.2, 22.8, 26.0, 29.4, 29.5, 29.7, 30.6, 31.9,
49.9, 67.3, 67.7, 128.8, 130.7, 144.8, 146.5, 150.0, 161.5. ES-MS
(+ve): m/z 194.0 [M - C8H17OSO3 ]+; ES-MS (-ve): m/z, 209.0
-
[C8H17OSO3]-.
3-(Butoxycarbonyl)-1-butylpyridinium octyl sulfate (7b).
1
Yield 93%. H NMR (DMSO d6): d 0.84–0.97 (m, 9H), 1.25–
1.52 (m, 16H), 1.70–1.80 (m, 2H), 1.87–1.97 (m, 2H), 3.64–3.69
(t, J = 6.6 Hz, 2H), 4.39–4.43 (t, J = 6.6 Hz, 2H), 4.69–4.74 (t,
J = 7.5 Hz, 2H), 8.26–8.30 (m, 1H), 8.97–9.00 (m, 1H), 9.27–
9.29 (m, 1H), 9.59 (s, 1H). 13C NMR (DMSO d6): d 13.2, 13.5,
13.8, 18.5, 18.7, 22.0, 25.5, 28.6, 28.7, 29.0, 30.0, 31.2, 32.7,
60.9, 65.4, 66.1, 128.4, 130.0, 145.0, 145.8, 147.9, 161.7. ES-MS
(+ve): m/z 236.2 [M - C8H17OSO3 ]+; ES-MS (-ve): m/z, 209.1
-
General procedure for the synthesis of pyridinium octyl sulfates
(1b, 2b, 5b, 6b, 7b and 8b)35
[C8H17OSO3]-.
The quaternary salt (2 mmol) was dissolved in water to obtain
a clear solution. The aqueous solution of quaternary halide
was treated with the aqueous solution of sodium octyl sulfate
(1.54 mmol in case of 1b, 2b and 5b or 2 mmol in case of 6b,
7b and 8b in 10 mL of water) and the resultant was stirred for
10 min. The product was isolated by solvent extraction using
dichloromethane (3 ¥ 10 mL). The extracts were dried over
anhydrous MgSO4 and evaporated under reduced pressure to
yield the required product.
3-(Butylcarbamoyl)-1-butylpyridinium octyl sulfate (8b).
Yield 87%. H NMR (DMSO d6): d 0.82–0.95 (m, 9H), 1.25–
1
1.60 (m, 18H), 1.88–1.98 (m, 2H), 3.30–3.37 (m, 2H), 3.65–3.69
(t, J = 6.6 Hz, 2H), 4.63–4.68 (t, J = 7.5 Hz, 2H), 8.23–8.28
(m, 1H), 8.89–8.91 (m, 1H), 8.98–9.02 (m, 1H), 9.18–9.20 (s,
1H), 9.43 (s, 1H). 13C NMR (CDCl3): d 13.5, 13.9, 14.2, 19.5,
20.4, 22.8, 26.0, 29.3, 29.4, 29.7, 31.2, 31.9, 33.8, 40.7, 62.4, 68.2,
128.4, 135.8, 143.7, 144.9, 146.5, 161.0. ES-MS (+ve): m/z 235.1
[M - C8H17OSO3 ]+; ES-MS (-ve): m/z, 209.1 [C8H17OSO3]-.
-
1
1-Butylpyridinium octyl sulfate (1b). Yield 90%. H NMR
General procedure for the synthesis of pyridinium triflimides (1c,
5c and 6c)
(CDCl3): d 0.84–0.89 (t, J = 6.8 Hz, 3H), 0.93–0.98 (t, J =
7.4 Hz, 3H), 1.26–1.45 (m, 12H), 1.61–1.71 (m, 2H), 1.94–
2.04 (m, 2H), 4.00–4.05 (t, J = 6.8 Hz, 2H), 4.76–4.81 (t, J =
7.4 Hz, 2H), 8.06–8.11 (m, 2H), 8.44–8.49 (m, 1H), 9.17–9.18
(m, 2H). 13C NMR (CDCl3): d 13.6, 14.2, 19.4, 22.7, 26.0, 29.3,
29.4, 29.7, 31.9, 33.8, 62.0, 67.8, 128.7, 145.2, 145.5. ES-MS
The quaternary halide (2 mmol) was dissolved in water
(10 mL) to obtain a clear solution. The aqueous solution
of quaternary halide was treated with the aqueous solution
of bis(trifluormethanesulfonimide) lithium salt (2.2 mmol,
0.631 g in 10 mL water) and the resultant was stirred for
10 min. The product was isolated by solvent extraction using
dichloromethane (2 ¥ 10 mL). The extracts were dried over
anhydrous MgSO4 and evaporated under reduced pressure to
yield the required product. As expected, all triflimide based ILs
were low viscosity liquids at room temperature.
(+ ve): m/z, 136.3 [M–C8H17OSO3 ]+; ES-MS (-ve): m/z, 209.3
-
[C8H17OSO3]-.
1-Butyl-3-methylpyridinium octyl sulfate (2b). Yield 93%. 1H
NMR (CDCl3): d 0.85–0.89 (t, J = 6.8 Hz, 3H), 0.93–0.98 (t, J =
7.2 Hz, 3H), 1.26–1.45 (m, 12H), 1.61–1.71 (m, 2H), 1.93–2.03
(m, 2H), 2.62 (s, 3H), 4.01–4.05 (t, J = 6.9 Hz, 2H), 4.74–4.79
88 | Green Chem., 2009, 11, 83–90
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1-Butylpyridinium triflimide (1c). Yield 97%. 1H NMR
(DMSO d6): d 0.89–0.94 (t, J = 7.4 Hz, 3H), 1.24–1.37 (m,
2H), 1.86–1.98 (m, 2H), 4.58–4.63 (t, J = 7.4 Hz, 2H), 8.13–
8.17 (m, 2H), 8.57–8.62 (m, 1H), 9.07–9.09 (m, 2H). 13C NMR
(DMSO d6): d 13.2, 18.7, 32.6, 60.6, 119.48 (–CF3), 128.1, 144.7,
145.4. ES-MS (+ve): m/z, 136.2 ([M - [N(SO2CF3)2]-)+; ES-MS
(-ve): m/z, 280.0 [N(SO2CF3)2]-.
General procedure for Diels–Alder reactions in BIL 6c
The dienophile (1.66 mmol) was added to 3-(butoxycarbonyl)-
1-methylpyridinium triflimide (6c) (0.5 mL) and the mixture was
stirred well for 1–3 min. Cyclopentadiene (2.33 mmol) was added
and the reaction mixture was stirred at room temperature for the
time specified in the Table 1. Diels–Alder adducts were extracted
with diethyl ether (3 ¥ 20 mL), the extracts were dried over
anhydrous MgSO4 and evaporated under reduced pressure to
yield the crude products. All crude products were purified using
column chromatography with ethyl acetate/petroleum spirits
(ranging from 5% to 30% ethyl acetate) as an eluent. The 1H and
13C NNMR spectra of these products were identical to those
previously reported in the literature.
1-(2-Ethoxycarbonyl)methylpyridinium triflimide (5c). Yield
1
93%. H NMR (DMSO d6): d 1.24–1.29 (t, J = 7.1 Hz, 3H),
4.22–4.29 (q, J = 7.1 Hz, 2H), 5.65 (s, 2H), 8.21–8.26 (m, 2H),
8.68–8.73 (m, 1H), 9.03–9.05 (m, 2H). 13C NMR (DMSO d6): d
13.8, 60.3, 62.3, 119.5 (-CF3), 127.8, 146.3, 146.7, 166.3. ES-MS
(+ve): m/z, 166.1 ([M - [N(SO2CF3)2]-)+; ES-MS (-ve) 280.0
[N(SO2CF3)2]-.
ISO 14593-Carbon dioxide head space test
3-(Butoxycarbonyl)-1-methylpyridinium
triflimide
(6c).
To evaluate the biodegradability of the test ILs, the ‘‘CO2
Headspace’’ test (ISO 14593) was also applied. This method
allows the evaluation of the ultimate aerobic biodegradability
of an organic compound in an aqueous medium at a given
concentration of microorganisms by analysis of inorganic
carbon. The test IL, as the sole source of carbon and energy,
was added at a concentration of 40 mg/L to a mineral salt
medium. These solutions were inoculated with activated sludge
collected from an activated sludge treatment plant, washed
and aerated prior to use and incubated in sealed vessels with
a headspace of air. Biodegradation (mineralization to carbon
dioxide) was determined by measuring the net increase in the
total organic carbon (TOC) levels over time compared with
unamended blanks. Sodium n-dodecyl sulfate (SDS) was used
as reference substance. The tests ran for 28 days. The extent of
biodegradation was expressed as a percentage of the theoretical
amount of inorganic carbon (ThIC) based on the amount of test
compound added initially.
Yield 92%. 1H NMR (CDCl3): d 0.96–1.01 (t, J = 7.4 Hz, 3H),
1.41–1.53 (m, 2H), 1.75–1.85 (m, 2H), 4.43–4.48 (t, J = 6.8 Hz,
2H), 4.52 (s, 3H), 8.12–8.16 (m, 1H), 8.93–8.95 (m, 2H), 9.14 (s,
1H). 13C NMR (DMSO d6): d 13.4, 18.5, 30.0, 48.3, 66.1, 119.5
(CF3), 127.9, 129.5, 144.7, 146.7, 148.8, 161.7. ES-MS (+ve):
m/z, 194.1 [M - [N(SO2CF3)2]-]+; ES-MS (-ve): m/z, 280.0
[N(SO2CF3)2]-.
General procedure for the synthesis of pyridinium
hexafluorophosphates (1d, 5d and 6d)36
The quaternary salt (2 mmol) was dissolved in water (10 mL) to
obtain a clear solution. The aqueous solution of quaternary
halide was treated with the aqueous solution of potassium
hexafluorophosphate (2.4 mmol, 0.405 g in 10 mL water) and
the resultant was stirred for 10 min. The product was isolated
by solvent extraction using dichloromethane (2 ¥ 10 mL). The
extracts were dried over anhydrous MgSO4 and evaporated
under reduced pressure to yield the desired product.
Acknowledgements
1-Butylpyridinium hexafluorophosphate (1d). Yield 89%. 1H
NMR (DMSO d6): d 0.89–0.94 (t, J = 7.4 Hz, 3H), 1.24–1.36
(m, 2H), 1.86–1.96 (m, 2H), 4.58–4.63 (t, J = 7.4 Hz, 2H), 8.12–
8.16 (m, 2H), 8.56–8.61 (m, 1H), 9.05–9.07 (m, 2H), 13C NMR
(DMSO d6): d 13.2, 18.7, 32.6, 60.7, 128.1, 144.7, 145.4. ES-MS
The authors thank Pfizer Global R & D, the Spanish Minis-
terio de Educacio´n y Ciencia (CTQ2007–60364/PPQ) and the
Australian Research Council (LX0561094) for financial support.
(+ve): m/z, 136.2 [M - PF6 ]+; ES-MS (-ve): m/z, 144.9 [PF6]-.
-
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(6d). Yield 86%. H NMR (DMSO d6): d 0.92–0.97 (t, J =
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(m, 5H), 8.22–8.27 (m, 1H), 8.95–8.98 (m, 1H), 9.16–9.18 (m,
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194.0 [M - PF6 ]+; ES-MS (-ve): m/z, 145.0 [PF6]-.
-
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©