Surface-active ionic liquids for micellar extraction of piperine from black pepper

Article abstract of DOI:10.5560/ZNB.2013-3196

We present the application of ionic liquid-aqueous micellar solutions as isolation media for the pharmaceutically active ingredient piperine from black pepper. Several surface-active ionic liquids including a biodegradable betaine derivative were used for the extraction of piperine, and a strong correlation between extraction yield and the critical micelle concentration of the respective ionic liquid was found. A scaled strategy for the isolation of piperine was developed that allowed recovery and recycling of the aqueous ionic liquid micellar solution for five runs without any loss in extraction efficiency.

Full text of DOI:10.5560/ZNB.2013-3196

Surface-active Ionic Liquids for Micellar Extraction of Piperine from
Black Pepper
Anna K. Ressmanna, Ronald Zirbsb, Martin Presslera, Peter Gaertnera, and
Katharina Bicaa
a
Institute of Applied Synthetic Chemistry, Vienna University of Technology, 1060 Vienna,
Austria
b
Group for Biologically Inspired Materials, Institute of Nanobiotechnology (DNBT), University
of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria
Reprint requests to Dr. K. Bica. Fax: +43 1 58801 16399. E-mail: katharina.bica@tuwien.ac.at
Z. Naturforsch. 2013, 68b, 1129 – 1137 / DOI: 10.5560/ZNB.2013-3196
Received July 23, 2013
We present the application of ionic liquid-aqueous micellar solutions as isolation media for the
pharmaceutically active ingredient piperine from black pepper. Several surface-active ionic liquids
including a biodegradable betaine derivative were used for the extraction of piperine, and a strong
correlation between extraction yield and the critical micelle concentration of the respective ionic
liquid was found. A scaled strategy for the isolation of piperine was developed that allowed recovery
and recycling of the aqueous ionic liquid micellar solution for five runs without any loss in extraction
efficiency.
Key words: Ionic Liquids, Micelles, Active Ingredient Isolation, Piperine, Biomass Processing,
Sustainable Chemistry
Introduction
vents such as ethanol, toluene or chlorinated hydrocar-
bons [9, 10]. This extraction process is not only time
Biomass feedstocks provide a unique and indispen- consuming and requires large amounts of often toxic
sible source for drug development and manufactur- solvents, but suffers from co-extraction of undesired
ing: Current estimations of the pharmaceutical mar- by-products such as gums, polysaccharides or essen-
ket indicate that approximately a third of all drugs tial oils. Additional purification steps are thus required
currently on the market is derived from natural prod- making the isolation and purification of a natural prod-
ucts [1]. Piperine ((2E,4E)-5-(1,3-benzodioxol-5-yl)- uct a large obstacle in any cost-efficient and sustainable
1-(1-piperidinyl)-,2,4-pentadien-1-one (1), a common drug manufacturing process.
alkaloid that is responsible for the pungent taste
In the past years, ionic liquids (ILs, salts with melt-
of pepper, is naturally occurring in Piper nigrum ing point < 100 ◦C) have emerged as alternative sol-
(6% – 9%), in Piper longum fruits (4%) and in Piper vents for biomass processing, as they provide unique
retrofractum (4% – 5%) [2]. Apart from its nutraceu- dissolution properties for biomass feedstocks. Based
tical uses, it has attracted attention for its inhibitory on the disruption of the intermolecular hydrogen-
influence on enzymatic drug biotransforming reactions bonded network up to ∼ 30 wt.- % cellulose can be
in the liver. The pharmacological properties of piper- solubilized in ionic liquids that are typically com-
ine are widespread: Piperine exhibits not only anti- posed of imidazolium head groups. This can be highly
fungal [3], antidiarrhoeal [4], anti-inflammatory [5], 5- beneficial for the extraction of valuable ingredients
lipoxygenase and cyclooxygenase-1 inhibitory activi- from biomass, as the tunability of ionic liquids al-
ties [6], but also serves as a positive GABAA recep- lows designing a tailor-made ionic liquid for a spe-
tor [7, 8].
cific extraction problem. While the use of ionic liq-
As most plant-derived active ingredients, piperine uids for biomass dissolution such as wood [11 – 15],
is typically isolated from cultivated plant material cellulose [16 – 19], lignin [20], chitin [21 – 24], silk
using excessive refluxing with volatile organic sol- fibroin [25], wool keratin [26], starch and zein pro-
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
tein [27], cotton and bamboo [28], chitosan [21], and cations and micelles are formed. While the physico-
cork biopolymers [29] has attracted tremendous inter- chemical properties of 1-alkyl-3-methyl-imidazolium
est, less attention has been paid to the isolation of valu- chlorides and bromides are reasonably well explored,
able ingredients using ionic liquids. Pioneering work so that critical micelle concentration values (CMC) are
was performed by Lapkin et al. in a study comparing available, applications remain limited. Yet we could
conventional solvents, ionic liquids, supercritical car- show that these micellar systems can be efficiently ap-
bon dioxide and fluorous solvents for the extraction of plied for synthesis and found enhanced reaction rates
the anti-malaria drug artemisinin from crude Artemisia for Diels-Alder reactions compared to the rates in
annua seeds [30]. This strategy has spread, and suc- neat water. A similar effect was reported by Coutinho
cessful examples for the application of ionic liquids as et al. who found increased enzyme activity of Can-
extraction media include the isolation of the pharma- dida antarctica lipase B (CaLB) in aqueous solutions
ceutically active steroid betulin from birch bark [31], of the ionic liquid 1-decyl-3-methyl-imidazolium chlo-
suberinic material from cork [32], the bioactive alka- ride, [C10mim]Cl [48].
loid S-(+)-glaucine from plant material of Glaucium
The concept of aqueous-ionic liquid systems as ex-
flavum Crantz (Papaveraceae) [33, 34], the flavonoid traction media has been only sparingly explored, al-
rutin [35], and the actives senkyunolide I, senkyuno- though promising work on the cellulose pretreatment
lide H and Z-ligustide [36], or shikonin and β,β0- with aqueous solutions of ionic liquids has been re-
dimethylacrylshikonin [37] from traditional Chinese ported by Welton et al. [49]. Cao et al. investigated
medical plants. Additionally, valuable essential oils, ultrasound-assisted extraction by ILs for the isolation
e. g. orange oil or rosmary oil could be directly dis- of piperine from white pepper [50]. Different aqueous
tilled from the ionic liquid media, thus allowing a sim- solutions of short-chain 1-alkyl-3-methyl-imidazolium
ple isolation of the pure volatile fragrance components bromides [Cnmim]Br with n = 3 and n = 4 were used
and a complete recovery of the ionic liquid [38 – 40]. in rather high concentration of 5 M. A strong influence
An elegant strategy was also developed by the group of the anion was observed, as the extraction efficiency
−
−
of MacFarlane, who used distillable ionic media for the decreased in the order BF4 > Br− > H2PO4
>
−
isolation of hydrolyzable tannins [41]. In some cases, PF6 which was explained by a reduced hydrophili-
the role of the ionic liquid is not limited to the func- city and water miscibility [50]. Although [C4mim]Br
tion as mere solvent, but it can directly take part in the performed significantly better than [C3mim]Br, longer
further transformation towards a drug intermediate, as chain lengths of the alkyl imidazolium backbone were
we could previously show for the reactive dissolution not investigated. Recently Coutinho et al. published
of star anise with Brønsted-acidic ILs that gave direct an elegant strategy for the isolation of caffeine from
access to an important intermediate for the manufac- guarana´ seeds using aqueous IL solutions [51].
turing of the anti-influenza drug Tamiflu™ [42].
Only few papers reported the exploration of the
While ionic liquids often proved to be superior to extraction of active ingredients with surface-active
conventional solvents in terms of extraction yield and ionic liquids. Yao et al. extracted different tanshi-
purity, their usage is still associated with a major draw- nones, namely tanshinone I, tanshinone IIA and cryp-
back: Ionic liquids are relatively expensive – at least totanshinone from Salvia miltiorrhiza bunge. Based
compared to conventional organic solvents – which on bromide anions, the chain length of the 1-alkyl-3-
may restrict their large-scale application as a bulk methyl-imdazolium cation was varied, as tanshinones
solvent. Our search for a compromise between eco- are lipophilic compounds. While [C8mim]Br failed to
nomic and environmental criteria got us interested in extract the active ingredients, the extraction yield in-
the use of aqueous-ionic liquid systems as reaction creased dramatically for tanshinone I and tanshinone
media for synthesis and catalysis [43]. Recent inves- IIA when the chain length was increasing from C10 to
tigations on the behavior of ionic liquids in the pres- C16 [52]. Microwave-assisted micellar extraction was
ence of water showed that certain ionic liquids can also successfully applied by Lin et al. in 2012 using
form aggregates in aqueous solution [44 – 47]. This is an aqueous two-phase system (ATPS) consisting of
the case for long-chain 1-alkyl-3-methyl-imidazolium [Cnmim]BF4/NaH2PO4 for the active ingredients hy-
chloride salts [Cnmim]Cl with n = 8 – 18, where the perin and isoquercitrin from Apocynum venetum; how-
apolar side chain stays in contact with that of other ever, better results were obtained with the butyl side
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
1131
chain rather than with the surface-active 1-methyl-3- Table 1. Influence of extraction conditions on the extraction
yield of piperine from black pepper using a 50 mM solution
of [C12mim]Cl in water.
octyl-imidazolium tetrafluoroborate [53].
In this paper, we show that IL-water micellar sys-
Entrya
Conditions
Piperine (wt.-%)b,c
tems might provide novel and high-yield but yet cost-
efficient extraction media for active ingredients. For
the extraction of piperine from ground black pep-
per, we have investigated micellar solutions of several
surface-active ionic liquids as extraction media and
provide a scaled strategy for the isolation of piperine
allowing recovery and recycling of the aqueous-ionic
liquid micellar solution.
1
2
3
4
5
6
1 h, 5 wt.- %
3 h, 5 wt.- %
24 h, 5 wt.- %
3 h, 1 wt.- %
3 h, 5 wt.- %
3 h, 10 wt.- %
3.42 ± 0.38
3.74 ± 0.19
4.64 ± 0.30
3.86 ± 0.27
3.74 ± 0.19
2.93 ± 0.11
a Performed with 50.0 ± 0.1 mg ground black pepper in 950 µL of
ionic liquid solution at 25 ◦C; b yield was determined via HPLC us-
ing phenol as internal standard; c average of three independent ex-
periments (mean ± STD, n = 3).
Results and Discussion
We have chosen a set of surface-active ionic liq- When investigating the influence of extraction time us-
uids based on common 1-alkyl-3-methyl-imidazolium ing a 50 mM [C12mim]Cl solution in water at 25 ◦C,
chlorides [Cnmim]Cl 2, 3 and 8 (Fig. 1) with alkyl we found that with increasing extraction time, extrac-
chain lengths varying from n = 10 to n = 14. As the tion efficiency also increased (Table 1, entries 1 – 3).
inherent toxicity and biodegradability of long-chain As a compromise between time demand and extrac-
imidazolium salts might restrict their application, we tion yield, we decided to work with an extraction time
also included a surface-active betaine-derived ionic of 3 h as already 3.74 wt.- % of piperine per black
liquid 9 that has been reported to be biodegradable pepper dry weight have been extracted within that
(Fig. 1).
time. When the ratio between biomass and ionic liq-
In an initial screening, we developed an HPLC strat- uid solution was further investigated, we found only
egy that allowed quantifying piperine in the presence a slight difference between 1% (w/v) and 5% (w/v)
of the aqueous ionic liquid systems to quickly iden- biomass in ionic liquid-containing solution. However,
tify optimum conditions for the extraction process. with a higher biomass loading of 10% (w/v) the ex-
Fig. 1. Structures of piperine (1) (left) and ionic liquids 2 – 9 used in this study (right).
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
traction efficiency decreased significantly, which might
be related to mixing problems (Table 1, entries 4 – 6).
Based on the optimum conditions, we turned our
attention towards the influence of different concentra-
tions of [C12mim]Cl in water. We found an interesting
correlation of the CMC of the respective ionic liquid
with the extraction yield of piperine: At low concen-
trations of ≤ 10 mM, only small amounts of piperine
< 0.20 wt.- % could be extracted, which is only
slightly higher than the extraction yield that was ob-
tained with pure water under similar conditions. How-
ever, as soon as the concentration of [C12mim]Cl
reached the CMC (15 mM) a significant increase in the
extraction efficiency was observed [54 – 56] (Fig. 2).
A similar pattern was observed when expanding the
range of ionic liquids. For solutions of [C10mim]Cl
(2), [C14mim]Cl (8) as well as the biodegradable
[C12betaine]Cl (9) the extraction efficiency increased
dramatically at concentrations higher than CMC of
the respective ionic liquid. For all ionic liquids, the
extraction yield eventually leveled off at concentra-
tions higher than 100 mM, and up to ∼ 4 wt.- % of
piperine could be extracted. We found that the in-
crease in the extraction efficiency can be correlated
with the chain length and found an increase oc-
curring in the order [C14mim]Cl (8) < [C12mim]Cl
(3) ≈ [C12betaine]Cl (9) < [C10mim]Cl (2). This again
is in accordance with literature data [43], as a lin-
ear relationship between the logarithm of CMC and
the number of carbon atoms n is found for 1-alkyl-
3-methyl-imidazolium-based ionic liquids [Cnmim]Cl.
In comparison to the large effect of the chain length
in the cation, the anion in the surface-active ionic
liquids [C12mim]X had less influence on the ex-
Fig. 2 (color online). Influence of the concentration of
surface-active ionic liquids in water on the extraction of
piperine from black pepper.
Table 2. Influence of different anions on the extraction yield
of piperine from black pepper using a 50 mM solution of
[C12mim]X in water.
Entrya
Ionic liquid solution
Piperine (wt.-%)b,c
1
2
3
4
5
50 mM [C12mim]OTf (5)
50 mM [C12mim]Cl (3)
50 mM [C12mim]Br (4)
50 mM [C12mim]N(CN)2 (6)
50 mM [C12mim]OAc (7)
2.28 ± 0.19
3.74 ± 0.19
3.08 ± 0.13
3.28 ± 0.33
3.35 ± 0.45
a Performed with 50.0 ± 0.1 mg ground black pepper in 950 µL of
ionic liquid solution at 25 ◦C; b yield was determined via HPLC us-
ing phenol as internal standard; c average of three independent ex-
periments (mean ± STD, n = 3).
traction efficiency. With the exception of the triflate tracted around 3.10 wt.- % and gave the lowest yield
anion (X = OTf, 5) that gave only moderate yields among the organic solvents screened here (Fig. 3).
of 2.28 wt.- %, all other anions including halides
The importance of the surface-activity of the ap-
(X = Cl− or Br−, 4), dicyanamide (X = N(CN)−, 6) plied ionic liquid solution is obvious when the extrac-
or acetate (X = OAc−, 7) were suitable for the ex- tion yield is compared with the yield of a 50 mM solu-
traction and gave comparable yields between 3.20 and tion of NaCl in water: Only 0.06 wt.- % could be iso-
3.74 wt.- % (Table 2).
lated here, which is even below the extraction yield
When comparing the extraction performance of with pure water, that reached 0.11 wt.- %. The influ-
micellar solutions of 1-alkyl-3-methyl-imidazolium- ence of aqueous ionic liquid solutions compared to
based ionic liquids, we found that these solutions can pure water is also visible from electron microscopy
compete with different conventional organic solvents that was performed on the recovered biomass after
reported in literature. The volatile and toxic solvents extraction. Although micellar solution of 1-alkyl-3-
such as chloroform, methanol and toluene gave only methyl-imidazolium based ionic liquids [Cnmim]Cl
slightly higher yields of 3.81 – 4.10 wt.- %, whereas did not completely dissolve biomass as we observed
the environmentally more benign butyl acetate ex- in our previous studies [31] with neat ionic liquids, we
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
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Table 3. Extraction efficiencies of pure ionic liquids
[C10mim]Cl, [C12mim]Cl and [C14mim]Cl.
Entrya
Ionic liquid
Piperine (wt.-%)b,c
1
2
3
[C10mim]Cl
[C12mim]Cl
[C14mim]Cl
3.74 ± 0.28
3.57 ± 0.28
3.52 ± 0.28
a Performed with 50.0 ± 0.1 mg ground black pepper in 950.0 ±
5.0 mg of pure ionic liquid at 80 ◦C; b yield was determined via
HPLC using phenol as internal standard; c average of three indepen-
dent experiments (mean ± STD, n = 3).
Consequently, it seems that complete solubiliza-
tion of the biopolymer matrix is not always neces-
sary for efficient extraction of the valuable ingredients:
When comparing the extraction yields of aqueous so-
lution of the ionic liquids [Cnmim]Cl with those ob-
tained with pure ionic liquids, we found that the mi-
cellar systems can be a superior alternative to the neat
ionic liquid (Table 3, entries 1 – 3). It should be noted
Fig. 3 (color online). Comparison of IL and conventional
solvents.
observed some changes in biomass morphology that that the extraction with pure ionic liquids had to be
could not be observed when pure water was used as ex- performed at 80 ◦C as [C12mim]Cl and [C14mim]Cl
traction media (Fig. 4). A similar effect was observed were solid at room temperature. Even at this temper-
by Coutinho et al. who investigated the extraction of ature, viscosity problems occurred with longer alkyl
caffeine from guarana´ seed and reported an increase in chains, and the extraction efficiencies decreased. Only
the ratio of broken cells to intact cells in the presence of [C10mim]Cl, which is liquid at room temperature
ionic liquid/aqueous mixtures, although the biomass gave yields comparable to those of aqueous micellar
was not completely dissolved [51].
solution.
Fig. 4. Electron microscopy of residual pepper after extraction with water (left) and with aqueous ionic liquid micellar solution
(right).
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
As previously optimized we worked in a 5% (w/v)
solution of ground black pepper. After extraction of
1.00 g ground black pepper with 19 mL of a 50 mM so-
lution of [C12betaine]Cl in water for 3 h at room tem-
perature, the remaining biomass was removed via fil-
tration. Once the biomass was removed, the micellar
solution was extracted with a small amount of envi-
ronmentally benign butyl acetate. We found that af-
ter extraction with only 5 mL butyl acetate piperine
was nearly quantitatively separated leaving less than
0.2 wt.- % piperine in the ionic liquid micellar solu-
tion. This allowed not only a quick and clean separa-
tion of piperine in excellent purity, but also the recov-
ery of the aqueous solution containing the ionic liq-
uid that could be directly used for four additional runs
without any loss in performance (Fig. 6).
Fig. 5 (color online). Scale-up strategy for the isolation of
piperine from black pepper.
Alternatively, the micellar solution containing piper-
ine can be directly subjected to any consecutive syn-
thetic modification towards piperine derivatives, which
will be the object of our future studies.
Conclusion
Aqueous-ionic liquids micellar solutions are effi-
cient extraction media for the isolation of active ingre-
dients and can overcome common problems of con-
ventional organic solvents. Based on the isolation of
piperine from black pepper, we have demonstrated that
the extraction efficiency of various aqueous-ionic liq-
uid micellar solutions strongly depends on the CMC
of the respective ionic liquid. Based on a biodegrad-
able betaine derivative, a simple and scalable isolation
procedure was developed, which allowed separation of
piperine from the extraction media and the recycling of
the aqueous solution for four times without loss in the
extraction efficiency.
Experimental Section
Fig. 6 (color online). Results of the scale-up and recycling.
Commercially available reagents and solvents were used
as received from Sigma Aldrich unless otherwise specified.
Ionic liquids [C10mim]Cl, and [C12mim]Cl [C12mim]Br
and [C14mim]Cl were prepared from freshly distilled N-
methylimidazole and alkyl chloride or alkyl bromide accord-
ing to the literature [57]. Solid [C12mim]Cl and [C14mim]Cl
were repeatedly crystallized from THF until colorless
crystals were obtained. Ionic liquids [C12mim]OTf [58],
[C12mim]N(CN)2 [59], [C12mim]OAc [60] have previously
been reported in literature and were prepared via metathesis
reaction of [C12mim]Cl with the corresponding silver salt of
Scaled procedure and reusability of the extraction
media
Once the optimum extraction conditions were iden-
tified, we turned our attention towards a scaled extrac-
tion process allowing not only the isolation of piperine,
but also the recovery of the micellar ionic liquid solu-
tion (Fig. 5).
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A. K. Ressmann et al. · Ionic Liquids for Micellar Extraction of Piperine from Black Pepper
1135
the anion. All ionic liquids were dried for at least 24 – 48 h at tals in 88% yield. – 1H NMR (CDCl3): δ = 0.81 (3H, t,
50 ◦C and 0.01 mbar before use and were stored under argon. J = 7.0 Hz, -C11H22-CH3), 1.19 (18H, m, -C2H4-C9H18
-
1H and 13C NMR spectra were recorded on a Bruker AC CH3), 1.58 (2H, t, J = 6.7 Hz, -CH2-CH2-C10H21), 3.60 (9H,
400 spectrometer at 400 and 100 MHz, respectively, using s, N-(CH3)3), 4.10 (2H, t, J = 7.0 Hz, -CH2-C11H23), 5.01
the solvent peak as reference. J values are given in Hz. 13
C
(2H, s, Cl-CH2-CO). These data were in accordance with the
NMR spectra were run in proton-decoupled mode.
literature [62].
For the determination of piperine a Phenomenex Luna
Extraction procedure for IL solutions
10 µm C18 100 A column (250 × 4.60 mm) was used with
CH3CN/H2O 55/45 as solvent and a flow of 1 mL min−1
;
A suspension of black pepper in aqueous IL solution
(1 wt.- %: 10.0 mg pepper, 990 mg IL solution; 5 wt.- %:
50 mg pepper, 950 mg IL solution; 10 wt.- %: 100 mg pepper,
900 mg IL solution) was stirred at 25 ◦C for 3 h. A sample of
100 µL was taken from the supernatant and diluted to 5 mL
with the IL solution. An aliquot of 1 mL was taken, mixed
with 200 µL of internal standard (60.0 mg phenol in 100 mL
of water) filtered over a 0.2 µm syringe filter and measured
immediately via HPLC. Results are based on three indepen-
dent experiments.
detection was done at 271 nm, at 30 ◦C column oven temper-
ature, 4 ◦C tray temperature. Retention times were 4.07 min
for phenol and 9.2 min for piperine. Standard calibrations
were performed for aqueous and organic extraction.
Dodecyl 2-chloroacetate
Dodecanol (14.18 g, 76.10 mmol) and chloroacetyl chlo-
ride (11.17 g, 98.90 mmol) were dissolved in 50 mL of an-
hydrous dichloromethane under argon and chilled to 0 ◦C.
Triethylamine (10.00 g, 98.90 mmol) was added dropwise.
The solution was stirred at room temperature over night until
TLC indicated full conversion. The solution was diluted with
50 mL of water and extracted with dichloromethane. The
combined organic layers were successively washed with 2 N
HCl, saturated NaHCO3 and brine. The solution was dried
over Na2SO4, filtered and evaporated to dryness. Dodecyl
2-chloroacetate was obtained as a light-yellow oil in 95%
yield and used as obtained. – 1H NMR (CDCl3): δ = 0.88
(3H, t, J = 6.4 Hz, -C11H22-CH3), 1.26 (18H, m, -C2H4-
C9H18-CH3), 1.67 (2H, t, J = 6.6 Hz, -CH2-CH2-C10H21),
4.06 (2H, s, Cl-CH2-CO), 4.19 (2H, t, J = 0.7 Hz, -CH2-
C11H23). These data were in accordance with the litera-
ture [61].
Scaled procedure for the isolation of piperine
Ground black pepper (1.000 g) was stirred with 19 mL of
a 50 mM solution of [C12betaine]Cl in water at 25 ◦C for 3 h.
After filtration the solution was extracted 3 times with a to-
tal volume of 5 mL of n-butyl acetate. Samples of 100 µL
were taken from the aqueous layer, and HPLC measurements
carried out before and after extraction with butyl acetate to
quantify the amount of piperine in the micellar solution. The
remaining micellar solution was directly used for the next
extractions step without further purification.
For isolation of piperine, the combined organic layers
were dried over Na2SO4, filtered and evaporated to dry-
ness. – 1H NMR (CDCl3): δ = 1.59 – 1.63 (6H, m, N-
CH2-CH2-CH2-CH2-CH2-), 3.54 – 3.64 (4H, m, N-CH2-
CH2-CH2-CH2-CH2-), 5.98 (2H, s, O-CH2-O), 6.43 (1H, d,
J = 15.1 Hz, N-CO-CH), 6.72 – 6.99 (5H, m, Ph-H, Ph-CH-
CH ), 7.35 – 7.54 (1H, m, N-CO-CH-CH). These data are in
accordance with the literature [63]. Results are based on two
independent experiments.
2-(Dodecyloxy)-N,N,N-trimethyl-2-oxoethanaminium
chloride, [C12betaine]Cl (9)
Dodecyl 2-chloroacetate (5.39 g, 20.51 mmol) was dis-
solved in 15 mL anhydrous THF. A solution of trimethyl-
amine in THF (102.5 mmol) was added dropwise at room
temperature. After stirring over night the precipitate was col-
lected via filtration and washed with anhydrous THF and an-
hydrous diethyl ether. After drying in vacuo (2×10−2 mbar)
Acknowledgement
A. K. R. is a recipient of a DOC-fFORTE-fellowship of
overnight, [C12betaine]Cl (9) was obtained as colorless crys- the Austrian Academy of Sciences.
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