A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

Article abstract of DOI:10.3762/bjoc.10.142

An efficient synthetic route toward the preparation of a complete series of monosubstituted tetraalkylammonium cyclodextrin (CD) derivatives is presented. Monotosylation of native CDs (α-, β-, γ-) at position 6 gave the starting material. Reaction of monotosylate (mono-Ts-CD) with 45% aqueous trimethylamine gave CDs substituted with one cationic functional group in a single step. Derivatives equipped with a substituent containing two cationic sites separated by an ethylene or a propylene linker were prepared by reacting mono-Ts-CD with neat N,N,N'-trimethylethane-1,2-diamine or N,N,N'- trimethylpropane-1,3-diamine and subsequent methylation by CH₃I in good yields. Finally, analogues bearing a moiety with three tetraalkylammonium sites were synthesized by reacting mono-Ts-CD with bis(3-aminopropyl)amine and subsequent methylation. The majority of the presented reactions are very straightforward with a simple work-up, which avoids the need of chromatographic separation. Thus, these reactions are suitable for the multigram-scale production of monosubstituted cationic CDs. 2014 Popr et al;.

Full text of DOI:10.3762/bjoc.10.142

A complete series of 6-deoxy-monosubstituted
tetraalkylammonium derivatives of α-, β-, and
γ-cyclodextrin with 1, 2, and 3 permanent
positive charges
Martin Popr1, Simona Hybelbauerová2 and Jindřich Jindřich*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 1390–1396.
1Department of Organic Chemistry, Faculty of Science, Charles
doi:10.3762/bjoc.10.142
University in Prague, Hlavova 8, 128 40, Prague 2, Czech Republic,
Fax: +420 22195 1326 and 2Department of Teaching and Didactics of
Chemistry, Faculty of Science, Charles University in Prague, Hlavova
Received: 31 October 2013
Accepted: 15 May 2014
Published: 18 June 2014
8, 128 40, Prague 2, Czech Republic
Email:
Associate Editor: H. Ritter
Jindřich Jindřich* - jindrich@natur.cuni.cz
©
2014 Popr et al; licensee Beilstein-Institut.
*
Corresponding author
License and terms: see end of document.
Keywords:
cationic; cyclodextrins; monosubstitution; regioselectivity;
tetraalkylammonium derivatives
Abstract
An efficient synthetic route toward the preparation of a complete series of monosubstituted tetraalkylammonium cyclodextrin (CD)
derivatives is presented. Monotosylation of native CDs (α-, β-, γ-) at position 6 gave the starting material. Reaction of monotosy-
late (mono-Ts-CD) with 45% aqueous trimethylamine gave CDs substituted with one cationic functional group in a single step.
Derivatives equipped with a substituent containing two cationic sites separated by an ethylene or a propylene linker were prepared
by reacting mono-Ts-CD with neat N,N,N’-trimethylethane-1,2-diamine or N,N,N’-trimethylpropane-1,3-diamine and subsequent
methylation by CH3I in good yields. Finally, analogues bearing a moiety with three tetraalkylammonium sites were synthesized by
reacting mono-Ts-CD with bis(3-aminopropyl)amine and subsequent methylation. The majority of the presented reactions are very
straightforward with a simple work-up, which avoids the need of chromatographic separation. Thus, these reactions are suitable for
the multigram-scale production of monosubstituted cationic CDs.
Introduction
Cyclodextrins (CDs) are cyclic oligosaccharides with the shape trin and are composed of 6, 7 or 8 D-glucopyranose units, res-
of a hollow truncated cone, first described in 1891 by Villiers pectively. The most commonly utilized feature of native CDs is
[
1]. Naturally occurring CDs are named α-, β- and γ-cyclodex- their ability to form noncovalent inclusion complexes with a
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
wide range of guest molecules [2]. In the majority of industrial Single-isomer permanently charged cationic CD derivatives
applications, natural CDs serve as encapsulation agents with a proved to serve as excellent chiral selectors in capillary zone
high affinity toward suitable lipophilic organic guests [3]. The electrophoresis (CZE) [18,19] and as catalysts of chemical reac-
main areas of use of native CDs and their derivatives are drug tions [20,21]. The synthesis of some cationic derivatives of
transportation [4] and solubilization [5], catalysis [6] and β-CD have already been described in the literature (namely
enzyme mimics [7].
6I-(N,N,N-trimethylammonio)-6I-deoxy-β-cyclodextrin [21] and
I-(N,N,N’,N‘,N‘-pentamethylethane-1,2-diammonio)-6I-deoxy-
6
Chemically modified CDs [5,8] are prepared in order to reach β-cyclodextrin) [22]. However, the literature lacks a detailed
specific chemical and physical properties, e.g., solubility or synthetic protocol, the optimization, or the full characterization
their binding behavior [9]. Many different CD derivatives have of the products. Furthermore, α- and γ-CDs monofunctional-
been described in the literature, but most of the preparations ized with a tetraalkylammonium group have never been
suffer from the polydispersity of the products, low yields and reported before. Therefore, we decided to develop robust reac-
poor selectivity due to the large number of hydroxy groups. tion sequences for the preparation of complete sets (α-, β-, γ-) of
Among the useful derivatizations are, for example, permethyla- single-isomer monosubstituted quaternary ammonium CD
tion [10], acetylation [11] or hydroxypropylation [12] and derivatives with 1, 2 or 3 permanent positive charges, suitable
perfacial substitution of all primary 6-OH hydroxy groups by for high-scale production.
iodine [13]. The products of these reactions are easily acces-
sible in high amounts and are used in the pharmaceutical Results and Discussion
industry [14] or as precursors for further derivatizations.
This article presents the synthesis of a complete series of mono-
substituted CD derivatives with a permanent positive charge
Monosubstituted CDs, i.e., CDs with only one hydroxy group (Figure 1).
substituted, are the most difficult to prepare, but can find use in
Synthesis of monotosylated CDs as the
many applications. The selectivity of the substitution can be
achieved by taking advantage of the different reactivity of pri- starting material
mary and secondary hydroxy groups. Reactions employing one The most crucial and scope-limiting step of the reaction
equivalent of derivatizing agent along with an excess of base sequence was the introduction of a suitable leaving group in the
lead to the 6I-O-substituted products, while the preparation of position 6 of the native CD. For this purpose, the selective
2
I-O-substituted derivatives [15] takes advantage of the highest monotosylation of the free CD was chosen. Several methods for
acidity of 2-OH hydroxy groups. A widely used methodology 6-O-tosylation have already been published [23-26]. Unfortu-
that leads to a variety of 6I-O-substituted analogues is the reac- nately, most of them lead to mixtures of mono- and multi-tosy-
tion with p-toluenesulfonic chloride [16] or p-toluenesulfonic lated products, which cannot be separated by precipitation from
anhydride [17] and an excess of base, which affords 6I-O-tosyl- acetone or crystalization from water. So we developed a new
CD. This can be converted into the desired product by a reac- chromatography-free method for the purification of the reaction
tion with an appropriate nucleophile.
mixture by crystalization. Monosubstitution of β-CD was
Figure 1: Schematic representation of the prepared sets of permanently charged CD derivatives.
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
carried out by the reaction of p-toluenesulfonic anhydride in described in 1978 by Matsui et al. [21] and comprised the reac-
aqueous NaOH as described previously in literature [17]. The tion of mono-Ts-β-CD with trimethylamine solution in DMF.
reaction yielded a mixture of monosubstituted product 6I-O-p- Their procedure afforded the product 4 in only 42% yield,
toluenesulfonyl-β-cyclodextrin (1), unreacted β-CD, and some which may have been caused by the high amount of byproducts
highly-substituted derivatives, which needed to be separated in possibly formed by the decomposition of DMF or by the formy-
order to receive pure tosylate 1. This fact is omitted in the orig- lation side reactions. The authors recovered pure 4 after lengthy
inal paper [17]. We used a strategy based on the repeated crys- chromatographic separation on a carboxymethylcellulose
tallization in a MeOH/H2O (1:1 v/v) mixture, which affords column, involving the collection of 150 fractions. We decided
pure 1 after the third run in the satisfying overall yield of 26%. to optimize the reaction conditions with the goal of improving
TLC and detection by carbonization proved to be a very simple the yield and avoiding the chromatography altogether. 45% v/v
yet very sensitive method to follow the purity of the tosylates.
aqueous solution of trimethylamine, which is cheap and
commercially available, was used (Scheme 1). Only two com-
For the monotosylation of α- and γ-CDs the reaction in water pounds were found in the reaction mixture – product 4 and
offers no advantage due to the high solubility of the products in byproduct 3,6-anhydro-β-cyclodextrin. The product 4 was
aqueous solution (to precipitate out during the work-up) and the easily separated on a short column of strong cation-exchange
lower regioselectivity [27]. A conventional reaction with TsCl resin in a H+ cycle by flushing the column firstly with H2O to
in pyridine [16] was used instead. Similarly as in the case of elute 3,6-anhydro-β-cyclodextrin and then with aqueous
β-CD mentioned above, this reaction provided a mixture of NH4HCO3 to elute the product. The yield of the reaction was
products with several degrees of substitution. The recently 71%. Derivatives of α- and γ-cyclodextrin (5 and 6) with one
published purification procedure [16] yielded just this mixture. tetralkylammonium group were prepared by the identical proce-
The purification on a column of activated charcoal was also dure in 58% and 54% yields, respectively (Scheme 1).
described [28]. We found the most convenient purification
Synthesis of CD derivatives monosubstituted
method to obtain 6I-O-p-toluenesulfonyl-α-cyclodextrin (2) and
6
I-O-p-toluenesulfonyl-γ-cyclodextrin (3) is flash column chro- with quaternary diamine
matography on a reverse phase C18 column with a step 6I-(N,N,N’,N‘,N‘-Pentamethylethane-1,2-diammonio)-6I-deoxy-
gradient. The use of this method allowed for the recovery of β-cyclodextrin diiodide (PEMEDA-β-CD, 12) was prepared by
about 40% of the starting α- or γ-CD by flushing the column modification of the procedure described by Nzeadibe et al. [22],
with 10% MeOH. Pure monotosylated product is then eluted by which neither provides the full NMR assignment of the inter-
2
5% MeOH. This strategy affords compounds 2 and 3 in a very mediates and the product nor the yields of the reactions. In the
high purity and in sufficient yields of 32% and 50%, respective- first step, reagent N,N,N‘-trimethylethane-1,2-diamine (7) was
ly (after subtraction of the recovered native CD).
easily prepared in one step by the published synthetic protocol
29], from inexpensive N-(2-chloroethyl)dimethylamine
[
Synthesis of monotrimethylammonio CD
derivatives
hydrochloride and MeNH2 (40% solution in H2O) (Scheme 2).
In the next step, mono-Ts-β-CD reacts with 7 to obtain inter-
A procedure for the preparation of 6I-(N,N,N-trimethylam- mediate 6I-((2-(dimethylamino)-1-(methyl)ethyl)amino)-6I-
monio)-6I-deoxy-β-cyclodextrin bicarbonate (4) has been deoxy-β-cyclodextrin (9) (Scheme 3). The advantage of this
Scheme 1: Synthesis of monotrimethylammonio-CD derivatives.
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
be precipitated from propan-1-ol. Instead, we employed precipi-
tation from acetone with the subsequent separation of the
byproduct (p-toluenesulfonic acid) on a short column of strong
cation exchanger. This may be the reason of the lower yields of
compounds 10 and 11.
We discovered that compound 12 and its analogues 13 and 14
are liable to decomposition by a Hofmann elimination in
aqueous media, when subjected to higher temperatures or bases.
The degradation can be monitored by TLC, where the decompo-
Scheme 2: Preparation of diamines 7 and 8 as reagents for further
synthesis [29].
conversion is the absence of a solvent. Also, the unreacted 7 can sition product (olefin) was clearly visible. We decided to
be recycled from the reaction mixture by vacuum distillation. prepare another novel series of derivatives, where the two
Pure intermediate 9 was then obtained in 93% yield by simple tetraalkylammonium groups are separated by a propylene linker
precipitation of the reaction mixture from propan-1-ol. In the instead of the ethylene one (Scheme 4). The same synthetic
final step, 9 was quaternized by methyl iodide in DMF. The protocol as for the preparation of 12 and its α- and γ-analogues
reaction produced pure PEMEDA-β-CD after precipitation of was employed, but with N,N,N‘-trimethylpropane-1,3-diamine
the compound from acetone, without the need of any purifica- (8). Products 18, 19 and 20 with a linker between the charged
tion, in an excellent yield of 98%. PEMEDA derivatives of α- nitrogen atoms (PEMPDA series) which is one methylene unit
and γ-CDs were prepared by the procedure analogous to the longer proved to be more stable and resistant toward the
preparation of PEMEDA-β-CD (Scheme 3). The only deviation Hofmann elimination. Some preliminary measurements were
was the purification of intermediates 10 and 11, which cannot performed and revealed a decomposition half-time about 2×
Scheme 3: Synthesis of PEMEDA-CD derivatives.
Scheme 4: Synthesis of PEMPDA-CD derivatives.
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
longer for the series with a propylene linker. Again, yields of (Scheme 5) which would be used for the quaternization of the
the products are very satisfactory, especially for β-CD deriva- tertiary amine intermediate. The reaction sequence for the
tives.
preparation of 24 involved a 4-step protocol. In the first step,
one hydroxy group of ethylene glycol was substituted by tosy-
The decomposition kinetics measurement was carried out in an late to yield 92% of 2-hydroxyethyl-4-methylbenzenesulfonate
NMR tube at 80 °C with 1 equivalent of NaOH as a base and a (21). Next, compound 22 was prepared by a nucleophilic substi-
reaction time of 20 h. A 1H NMR spectrum was acquired every tution with sodium azide. The product of this reaction was not
hour. Integrals of the signals of the H1 protons of CD were isolated due to its possible explosive character, but was directly
compared to integrals of the signals of the N-CH3 protons, subjected to the tosylation to yield 23 [31]. Finally, compound
which were disappearing in time due to the Hofmann elimina- 24 was prepared by means of the Finkelstein reaction (which
tion. Decomposition half-times were estimated to be 3 and 7 h was already published [32]) in 96% yield.
for compounds 12 and 18, respectively.
We presumed that the alkylation of intermediate 9 by 24 in dry
Synthesis of CD derivatives monosubstituted
DMF would result in the product substituted on both nitrogens,
with a quaternary diamine bearing an
azidoethane function
but unfortunately the MS spectra revealed that only one
nitrogen atom gets substituted. We tried different conditions (up
Analogues of PEMEDA and PEMPDA-β-CD with an to 50 equivalents of 24, different sterically hindered bases,
azidoethane function attached to the terminal quaternary ammo- higher temperature) to achieve a conversion, but always only
nium nitrogen were prepared as a basis for further derivatiza- one azidoethane group was bound, possibly for steric reasons.
tion. The azide functional group is reactive and can be used, for So we decided to use a two-step procedure, which involved the
example, for the attachment of various substituted acetylenes by attachment of 24 in the first step and the quaternization by MeI
a Huisgen 1,3-dipolar cycloaddition [30] (most popular ‘click in the second step, without the need of the isolation of the inter-
reaction’) or the reduction to the amine. Our strategy involved mediate (Scheme 6). This strategy afforded compounds 25 and
the synthesis of the alkylation agent 1-azido-2-iodoethane (24) 26 in 98% and 94% yields, respectively.
Scheme 5: Synthesis of 1-azido-2-iodoethane.
Scheme 6: Synthesis of azidoethane-containing derivatives of PEMEDA and PEMPDA-β-CD.
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
Synthesis of CD derivatives monosubstituted
with a quaternary triamine
pounds 30, 32 and 33 were obtained as triacetates after the
purification on a silica gel column with a HOAc containing
To complete the series of cationic CD derivatives, a set of CDs eluent.
monosubstituted with permethylated linear triamine was
prepared (Scheme 7). The dry mono-Ts-β-CD reacted in the Conclusion
first step with diethylenetriamine or bis(3-aminopropyl)amine In summary, a complete series of permanently positively
in order to produce intermediates 27 and 28, respectively. α- charged monosubstituted CD (α-, β-, γ-) derivatives were
and γ- analogues 29 and 30 were prepared by an identical prepared. The synthesis was realized by the introduction of a
procedure in yields around 70%. Different routes were substituent with one, two or three tetraalkylammonium
explored, and the best results were achieved by a modified groups on position 6 of native CD. Some reactions on β-CD
procedure described by Tabushi et al. [33] (for β-CD only), were carried out by modification of already published pro-
which is a solvent-free reaction of the monotosylate with an cedures, but the majority of the products have not been
excess of liquid triamine. The unreacted liquid triamine can be described in the literature yet. Most of the products were
recovered from the reaction mixture by vacuum distillation and obtained by simple conversions, in high yields and without
used repeatedly. Pure intermediates 27 and 28 were obtained the need of chromatographic purification. The complete
after the elution with aqueous NH4OH, from a short column of characterization of the products is given, along with the
strong cation exchanger in hydrogen form, in 70% and 74% unambiguous assignment of the positions of substituents by 2D
yields, respectively. The derivative of γ-CD, compound 30, NMR techniques. We believe that the products presented in this
contained some trace amounts of impurities and needed to be article will find their use as chiral selectors in CZE. They offer
further purified on a silica gel column. In the following step, the the possibility to choose the number of charges to tune
installed triamine was quaternized by methylation with MeI. To the electrophoretic mobility. Furthermore, the diameter of the
achieve a full conversion, the use of a sterically hindered base CD cavity can be modified so that the strength of the
was necessary. First, we attempted to methylate intermediate 27 interaction with the isomers to be separated is adjustable
containing a diethylenetriamine moiety. Different bases to the task at hand. The study of the use of the
(
K2CO3, 2,6-lutidine, 2,4,6-collidine and DBU) and tempera- prepared derivatives for chiral separations in CZE is currently
tures (from rt to 50 °C) were tested, but we were not able to ongoing.
achieve a full conversion and the fraction of the product 27 in
the reaction mixture was not stable either. Similarly, as in the
Supporting Information
case of PEMEDA derivatives, 27 is vulnerable toward decom-
position by a Hofmann elimination. For this reason derivative
Supporting Information File 1
File Name: S1.pdf.
2
8, which has bound bis(3-aminopropyl)amine in position 6 of
β-CD, was prepared. In this derivative charged nitrogen atoms
are separated by a longer propylene linker. Presumable, this was
the reason that the methylation of this intermediate was more
efficient, reached a full conversion after 20 h, and provided pure
Experimental part and copies of 1H and 13C NMR spectra
of prepared compounds.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-142-S1.pdf]
3
1 after simple purification on cation-exchange column. Com-
Scheme 7: Synthesis of CD derivatives monosubstituted with a quaternary triamine moiety.
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Beilstein J. Org. Chem. 2014, 10, 1390–1396.
2
2
2
2
3
6.Tripodo, G.; Wischke, C.; Neffe, A. T.; Lendlein, A. Carbohydr. Res.
Acknowledgements
2013, 381, 59–63. doi:10.1016/j.carres.2013.08.018
This research was supported by the Ministry of Education,
Youth, and Sports of the Czech Republic (project No.
MSM0021620857) and by the Ministry of Industry and Trade
of the Czech Republic (project No. FR-TI3/370).
7.Takahashi, K.; Hattori, K. J. Inclusion Phenom. 1984, 2, 661–667.
doi:10.1007/BF00662233
8.Melton, L. D.; Slessor, K. N. Carbohydr. Res. 1971, 18, 29–37.
doi:10.1016/S0008-6215(00)80256-6
9.De Costa, B. R.; Radesca, L.; Di Paolo, L.; Bowen, W. D.
J. Med. Chem. 1992, 35, 38–47. doi:10.1021/jm00079a004
0.Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001,
References
1
.
Villiers, A. C. R. Hebd. Seances Acad. Sci. 1891, 112, 536–538.
Connors, K. A. Chem. Rev. 1997, 97, 1325–1358.
doi:10.1021/cr960371r
4
0, 2004–2021.
doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO
2-5
2.
;
3.
4.
5.
6.
7.
8.
9.
Hedges, A. R. Chem. Rev. 1998, 98, 2035–2044.
doi:10.1021/cr970014w
3
3
3
1.Demko, Z. P.; Sharpless, K. B. Org. Lett. 2001, 3, 4091–4094.
doi:10.1021/ol010220x
Laza-Knoerr, A. L.; Gref, R.; Couvreur, P. J. Drug Targeting 2010, 18,
2.Khoukhi, M.; Vaultier, M.; Carrié, R. Tetrahedron Lett. 1986, 27,
645–656. doi:10.3109/10611861003622552
1031–1034. doi:10.1016/S0040-4039(86)80040-5
Szejtli, J. J. Inclusion Phenom. Mol. Recognit. Chem. 1992, 14, 25–36.
doi:10.1007/BF01041363
3.Tabushi, I.; Shimizu, N.; Sugimoto, T.; Shiozuka, M.; Yamamura, K.
J. Am. Chem. Soc. 1977, 99, 7100–7102. doi:10.1021/ja00463a073
Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997–2012.
doi:10.1021/cr970011j
Marinescu, L.; Bols, M. Trends Glycosci. Glycotechnol. 2009, 21,
3
09–323. doi:10.4052/tigg.21.309
Khan, A. R.; Forgo, P.; Stine, K. J.; D’Souza, V. T. Chem. Rev. 1998,
8, 1977–1996. doi:10.1021/cr970012b
License and Terms
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Ashton, P. R.; Boyd, S. E.; Gattuso, G.; Hartwell, E. Y.; Koeniger, R.;
Spencer, N.; Stoddart, J. F. J. Org. Chem. 1995, 60, 3898–3903.
doi:10.1021/jo00117a049
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
1
1
1
1
1
1
1
1
1
1
0.Ciucanu, I.; Kerek, F. Carbohydr. Res. 1984, 131, 209–217.
doi:10.1016/0008-6215(84)85242-8
1.Fügedi, P.; Nánási, P.; Szejtli, J. Carbohydr. Res. 1988, 175, 173–181.
doi:10.1016/0008-6215(88)84140-5
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
2.Pitha, J.; Milecki, J.; Fales, H.; Pannell, L.; Uekama, K. Int. J. Pharm.
1986, 29, 73–82. doi:10.1016/0378-5173(86)90201-2
3.Ashton, P. R.; Koniger, R.; Stoddart, J. F.; Alker, D.; Harding, V. D.
J. Org. Chem. 1996, 61, 903–908. doi:10.1021/jo951396d
4.Loftsson, T.; Brewster, M. E. J. Pharm. Pharmacol. 2010, 62,
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
1607–1621. doi:10.1111/j.2042-7158.2010.01030.x
5.Řezanka, M.; Jindřich, J. Carbohydr. Res. 2011, 346, 2374–2379.
doi:10.1016/j.carres.2011.08.011
doi:10.3762/bjoc.10.142
6.Tang, W.; Ng, S.-C. Nat. Protoc. 2008, 3, 691–697.
doi:10.1038/nprot.2008.37
7.Zhong, N.; Byun, H.-S.; Bittman, R. Tetrahedron Lett. 1998, 39,
2919–2920. doi:10.1016/S0040-4039(98)00417-1
8.Cai, H.; Nguyen, T. V.; Vigh, G. Anal. Chem. 1998, 70, 580–589.
doi:10.1021/ac970822n
9.Cucinotta, V.; Contino, A.; Giuffrida, A.; Maccarrone, G.; Messina, M.
J. Chromatogr., A 2010, 1217, 953–967.
doi:10.1016/j.chroma.2009.11.094
2
2
2
2
0.Matsui, Y.; Okimoto, A. Bull. Chem. Soc. Jpn. 1978, 51, 3030–3034.
doi:10.1246/bcsj.51.3030
1.Matsui, Y.; Ogawa, K.; Mikami, S.; Yoshimoto, M.; Mochida, K.
Bull. Chem. Soc. Jpn. 1987, 60, 1219–1223. doi:10.1246/bcsj.60.1219
2.Nzeadibe, K.; Vigh, G. Electrophoresis 2007, 28, 2589–2605.
doi:10.1002/elps.200700028
3.Brady, B.; Lynam, N.; O’Sullivan, T.; Ahern, C.; Darcy, R. Org. Synth.
2000, 220–223.
2
4.Byun, H.-S.; Zhong, N.; Bittman, R. Org. Synth. 2000, 225–228.
5.Law, H.; Benito, J. M.; Garcia Fernandez, J. M.; Jicsinszky, L.;
Crouzy, S.; Defaye, J. J. Phys. Chem. B 2011, 115, 7524–7532.
doi:10.1021/jp2035345
2
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