ISSN 1 3 4 9 - 4 8 4 8
num ber
159
CO N T E N T S
2
R es earch Ar ticl e
- Polymerizable ionic liquids:
Development to photo functional poly(ionic liquid) materials
Jun-ichi Kadokawa
Professor of Graduate School of Science and Engineering,
Kagoshima University
7
Chem is tr y Chat – Fo cu si ng o n t he E lements –
- Naturally Occurring Organic Fluorine Compounds
Kentaro Sato
10
Chem is tr y Chat –Vi si t to a S cho o l S ci ence La b –
13
Sho r t To pic: M o re ways to us e reagent s
- Visit to a Science Club:
Science Club at Rikkyo Ikebukuro Junior & Senior
High School (Part 2)
- Synthesis of Multi-substituted Olefins via SCOOPY Reaction
Haruhiko Taguchi
Tokyo Chemical Industry Co., Ltd.
15
N ew Pro d uc ts I nfo rm atio n :
- Novel Fluorescent Probe for Visualizing and
Detecting Trace Amounts of Cesium Particulates
- Heteroarenecarbonyl Cinchona Alkaloid Catalysts
- Sparteines as Chiral Ligands for Asymmetric Synthesis
- Fluoresceins for Fluorescent Labeling
- Bone Resorption Inhibitor
- Surfactant for Biochemistry
No.159
Research Article
Polymerizable ionic liquids:
Development to photo functional poly(ionic liquid) materials
Jun-ichi Kadokawa
Graduate School of Science and Engineering, Kagoshima University
1. Introduction
Ionic liquids (ILs) are regarded as low-melting analogous
of classical molten salts, which generally form liquids at
temperatures below the boiling point of water.1) The property
is owing to thermodynamically favorable because of the large
size and conformational flexibility of the ions. Over the past
decade or more, ILs have attracted much attention due to their
specific characteristics such as a negligible vapor pressure and
excellent thermal stability. Therefore, ILs have been employed
as substitutes of volatile organic solvents in a variety of organic
reactions, chemical processing, and extracting. The other
important advantage of ILs is the diverse structure and chemical
composition, which can be constructed by pairing any of a
variety of organic cations with a wide range of either organic or
inorganic anions (Figure 1). Common IL cations are ammonium,
phosphonium, pyridinium, imidazolium, and so on. Accordingly,
ILs have exhibited controllable physical and chemical
properties and specific functions because of a variety of such
ion pairs, and thus, been found for a wide range of applications
in practical fields such as catalysis and electrochemistry. 2)
Beyond the traditional applications of ILs, their interests are
also being extended to the researches related to biomolecules
such as naturally occurring polysaccharides because of specific
affinities of ILs for them. 3) Recently, furthermore, specific
photo functions of ILs have also been reported. In this article,
therefore, the author would like to review his advanced research
development on photo functional poly(ionic liquid)s by radical
polymerization of polymerizable ILs.
Cation structures
R'
R N R
R X
Ammonium
Br-
R'
R'
R P R
R X
N
X
R
Phosphonium Pyridinium
BF4-
Poly(ionic liquid)s (PILs), also called polymerized
ionic liquids or polymeric ionic liquids, refer to polymeric
compounds that feature an IL species in each monomer
repeating unit, connecting through a polymeric backbone, which
are obtained by polymerization of ILs having polymerizable
groups (polymerizable ILs).4) The major advantages for such
polymeric forms of ILs are enhanced stability, improved
processability, flexibility, and durability in applications as
practical materials. Polymerizable ILs as a source of PILs can
be available by incorporating polymerizable groups either at
anionic or at cationic site in the IL structure and which gave
the corresponding PILs by radical polymerization (Scheme
1). In the former case, polymerizable anions are ionically
exchanged with some anions of general ILs to produce the
polymerizable ILs. In the latter case, vinyl, (meth)acryloyl,
and vinylbenzyl groups have typically been employed as the
polymerizable group covalently attached to cationic sites.
1-Vinylimidazole is a commercially available reagent, and
thus 1-vinylimidazolium-type polymerizable ILs are facilely
prepared by its quarternization with a variety of alkyl halides.
The reaction of a commercial available vinylbenzyl chloride
(Scheme 2(a)) or bromoalkyl (meth)acrylates, which are
prepared from bromoalkanols with (meth)acryloyl chloride
(Scheme 2(b)), with 1-alkylimidazoles yields the corresponding
imidazolium-type polymerizable ILs.5) Furthermore, when the
reaction is carried out using 1-vinylimidazole, the polymerizable
ILs having two polymerizable groups are obtained. Because this
R"
Anion structures
Cl-
2.Polymerizable ionic liquids and poly(ionic
liquid)s
PF6-
NO3-
R N
N R'
X
Imidazolium
O
CF3 S O
O
F3CO2S
N
SO2CF3
Figure 1. Typical cation and anion structures of ionic liquids.
2
NC
N
CN
No.159
the practical materials. Furthermore, anionic exchange reaction
of the polymerizable ILs with the corresponding salts can
introduce the prospective anions.
type of ILs can be converted to insoluble and stable PILs with
cross-linked structure by radical polymerization (Scheme 3),
they have a highly potential as the source of the components in
(a)
R
HN
N
Radical polymerization
R'
R
n
HN
N
R'
(b)
Radical polymerization
n
N R
N
N
X
N R
X
O
Polymerizable groups =
O
O
CH2
O
Scheme 1. Polymerization of polymerizable ILs having a polymerizable group at anionic site (a) and cationic site (b).
(a)
R N
N
R N
N
Cl
Cl
(b)
R N
Br
N
O
m
R
O
N
N
m O
Br
O
R = alkyl, vinyl
Br
OH
m
+
Cl
O
Scheme 2. Typical synthetic procedures for polymerizable ILs having vinylbenzyl (a) and (meth)acrylate (b) groups.
O
N
O
N
X
Radical polymerization
N
m
N
X
O
O
n
Cross-linked insoluble PIL
Scheme 3. Polymerization of a polymerizable IL having two polymerizable groups.
3
No.159
3.Development of photo functional poly(ionic
liquid) materials
One of the major driving forces for the preparation
of PILs is to demonstrate their potential as electrolytes in
batteries and fuel cells. 6) For example, Ohno et al. reported
that radical polymerization of imidazolium-type polymerizable
ILs gave highly ion conductive flexible films. 7) Recently,
the author has reported the preparation of cellulose-PIL
composite materials by radical polymerization of appropriate
polymerizable ILs.8) Because the author found in this approach
that some polymerizable ILs exhibited ability to partially
disrupt crystalline structure of cellulose by swelling, cellulose
was first immersed in the ILs for swelling and then their insitu polymerization in the system was performed to obtain the
target composite materials. This approach was also applied to
other polysaccharides to produce the corresponding composite
materials.9)
As one of other unique and specific properties of ILs, it
has been reported that imidazolium-type ILs show excitationwavelength-dependent fluorescent behavior owing to the
presence of energetically different associated species. 10) The
author thus has considered that such ILs have a potential as
components to contribute to developing new fluorescent photo
functional materials. To provide the practical IL material
exhibiting unique fluorescent property, first, an attempt was
made to obtain a transparent imidazolium-type PIL film by
radical copolymerization of two polymerizable ILs, that is,
1-methyl-3-(4-vinylbenzyl)imidazolium chloride (1) and
1-(3-methacryloyloxy)propyl-3-vinylimidazolium bromide
(2) (Figure 2(a)); the former gives PIL with polystyrene-type
backbone and the latter acts as cross-linking agent due to the
presence of two polymerizable groups.11) These polymerizable
ILs were synthesized by quarternization of 1-methylimidazole or
1-vinylimidazole with the corresponding haloalkyl derivatives
according to Scheme 2. For the preparation of film form of PIL
(3), a solution of 1 and 2 (10:1), and a radical initiator, AIBN, in
methanol was sandwiched between two glass plates, and then,
the system was heated at 65 °C for 30 min and subsequently at
75 °C for 2 h to simultaneously occur the polymerization and
evaporation of methanol. The resulting cross-linked PIL (3) had
the film form with transparent appearance and exhibited blue
emission by UV light irradiation at 365 nm as shown in Figure
2(b) and (c), respectively. The resulting film showed excitationwavelength-dependent fluorescent behavior (Figure 2(d))
similar as that of the general imidazolium-type ILs such as a
well-known ionic liquid, 1-butyl-3-methyimidazolium chloride
(BMIMCl).
The author found that the fluorescence resonance-energytransfer (FRET)12) from BMIMCl as a donor to rhodamine 6G,
a representative red fluorescent dye, as an acceptor occurred by
excitation at wide wavelength areas in a solution of rhodamine
6G in BMIMCl because the aforementioned specific excitationwavelength-dependent fluorescent emissions of BMIMCl,
excited at each wavelength, were overlapped with an absorption
of rhodamine 6G. 13) Consequently, the emissions due to
rhodamine 6G appeared by excitation at the wide wavelength
areas in the solution. On the basis of this result, the author has
designed the PIL films which exhibit multicolor emissions
depending on combinations of the three primary colors. 14)
Besides rhodamine for red emission, for this purpose, the
following two fluorescent dyes, that is, 7-(diethylamino)coumarin-3-carboxylic acid (DEAC) and pyranine were
employed for green and blue emissions, respectively.
To incorporate these dye moieties in the PIL film, the
polymerizable rhodamine, DEAC, and pyranine (4–6) having
a methacrylate group were synthesized as follows. The direct
condensation of rhodamine B with 2-hydroxyethyl methacrylate
using a condensing agent gave the polymerizable rhodamine
derivative 4 (Scheme 4). The polymerizable DEAC derivative
5 was synthesized from DEAC chloride and 2-hydroxyethylmethacrylate according to the literature procedure (Scheme 5).15)
The reaction of pyranine with methacryloyl chloride gave the
polymerizable pyranine derivative 6 (Scheme 6).
Then, radical copolymerization of 1, 2, with 4, 5, or 6
was carried out to produce the PIL films 7, 8, and 9 carrying
respective dye moieties (Figure 3(a)). The fluorescence spectra
of the resulting films exhibited the respective dye emissions by
excitation at wide wavelength areas (260–400 nm). Because
fluorescent emissions of the aforementioned PIL film 3 were
partially overlapped with absorptions of the films 7–9, the
emissions of these films excited at 260–400 nm were owing
(a)
O
N
N
N
N
O
AIBN
O
Radical polymerization
O
Br
Cl
1
2
N
(10:1)
N
N
Cl
n
N
Br
m
PIL film (3)
Figure 2. Radical copolymerization of 1 with 2 by AIBN to produce PIL film 3 (a), Photographs of PIL film 3 (b), it under UV light
irradiation at 365 nm (c), and fluorescence spectra of PIL film 3 by excitation at 260–400 nm (d).
4
No.159
to either direct excitation of the dye moieties or FRET from
the units 1 and 2 to the dye moieties. Actually, these films 7–9
showed the red, green, and blue emissions by light irradiation at
365 nm, respectively (Figure 3(b)).
O
OH
O
+
O
DCC / DMAP
(condensing agent)
O
OH
O
O
O
1,2-Dichloroethane
N
2-Hydroxyethyl methacrylate
N
O
N
N
O
4
Cl
Rhodamine B
DCC =
N
DMAP =
C N
N
Cl
N
Scheme 4. Synthesis of polymeirzable rhodamine derivative 4.
O
O
Cl
N
O
+
O
O
O
O
HO
N
Pyridine
O
O
2-Hydroxyethyl methacrylate
O
O
5
DEAC chloride
Scheme 5. Synthesis of polymerizable DEAC derivative 5.
SO3Na
SO3Na
NaO3S
+
OH
Triethylamine
Cl
O
NaO3S
Methacryloyl chloride
SO3Na
O
DMF
O
SO3Na
Pyranine
6
Scheme 6. Synthesis of polymerizable pyranine derivative 6.
Polymerizable fluorescent dyes
(a)
O
O
N
N
N
N
O
Fluorescent dye
O
Br
Cl
1
2
Polymerizable fluorescent dyes (4 - 6)
O
O
O
AIBN
O
n
Fluorescent dye
Cl
Br
N
N
N
Fluorescent dye unit
N
m
Unit 1
Unit 2
PIL filmes carring unit 4; 7
unit 5; 8
unit 6; 9
unit 4 + 5; 10
unit 4 + 6; 11
unit 5 + 6; 12
unit 4 + 5 + 6; 13
(b)
Red
Green
Blue
Yellow
Magenta
Cyan
White
PIL film 7
PIL film 8
PIL film 9
PIL film 10
PIL film 11
PIL film 12
PIL film 13
Figure 3. Radical copolymerization of 1, 2, with polymerizable fluorescent dyes to produce PIL films carrying various combinations
of dye moieties (a) and their multicolor emissions by light irradiation at 365 nm.
5
No.159
By means of possible combinations among the above
red, green, and blue dyes, the PIL films exhibiting tunable
color emissions were synthesized. Three combinations of the
polymerizable dyes (4+5, 4+6, 5+6) were copolymerized with
1 and 2 by AIBN to give the PIL films 10-12 (Figure 3(a)). The
fluorescence spectra of the resulting films showed two kinds of
emissions due to the incorporated dye moieties by excitation at
260–400 nm. These results indicated that the respective dyes
in the films were individually emitted by the direct excitation
or FRET. The PIL film 13 carrying three dye moieties was also
prepared by copolymerization of the three polymerizable dyes
with 1 and 2. The fluorescence spectra of the obtained film
showed three kinds of emissions due to each dye by excitation
at 260–400 nm. The above PIL films having plural dye moieties
exhibited yellow, magenta, cyan, and white fluorescent
emissions by excitation at a sole wavelength according to the
combinations of the dyes (Figure 3(b)).
4. Conclusions
In this article, the author reviewed the preparation of
functional PILs by the radical polymerization of polymerizable
ILs. The prospective polymerizable ILs were synthesized by
simple reaction steps. Specifically, their radical polymerization
efficiently gave PILs, which showed the unique and specific
photo functions as same as those of the general ILs. New
polymerizable ILs will be designed and synthesized in the future
for the production of the further high performance PIL materials
by the polymerization.
Acknowledgement
The author is indebted to the co-workers, whose names
are found in references from his papers, for their enthusiastic
collaborations.
References
1)T. Welton, Chem. Rev. 1999, 99, 2071; J. S. Wilkes, Green
Chem. 2002, 4, 73; T. Erdmenger, C. Guerrero-Sanchez, J.
Vitz, R. Hoogenboom, U. S. Schubert, Chem. Soc. Rev. 2010,
39, 3317.
2)J. H. Davis, Chem. Lett. 2004, 33, 1072; S. G. Lee, Chem.
Commun. 2006, 1049; R. Giernoth, Angew. Chem. Int. Ed.
2010, 49, 2834.
3)O. A. E. Seoud, A. Koschella, L. C. Fidale, S. Dorn, T. Heinze,
Biomacromolecules 2007, 8, 2629; M. E. Zakrzewska, E. B.
Lukasik, R. B. Lukasik, Energy & Fuels 2010, 24, 737.
4)O. Green, S. Grubjesic, S. Lee, M. A. Firestone, J. Macromol.
Sci.: Part C: Polym. Rev. 2009, 49, 339; D. Mecerreyes,
Prog. Polym. Sci. 2011, 36, 1629; J. Yuan, D. Mecerreyes, M.
Antonietti, Prog. Polym. Sci. 2013, 38, 1009.
5)T. Fukushima, A. Kosaka, Y. Ishimura, T. Yamamoto, T.
Takigawa, N. Ishii, T. Aida, Science 2003, 300, 2072; J. Tang,
H. Tang, W. Sun, M. Radosz, Y. Shen, J. Polym. Sci. Polym.
Chem. 2005, 43, 5477; J. Tang, H. Tang, W. Sun, M. Radosz, Y.
Shen, Polymer 2005, 46, 12460.
6)H. Ohno, Electrochim. Acta 2001, 46, 1407; M. Yoshizawa,
W. Ogihara, H. Ohno, Polym. Adv. Technol. 2002, 13, 589; H.
Ohno, M. Yoshizawa, W. Ogihara, Electrochim. Acta 2004,
50, 255.
7)S. Washiro, M. Yoshizawa, H. Nakajima, H. Ohno, Polymer
2004, 45, 1577.
8)M. Murakami, Y. Kaneko, J. Kadokawa, Carbohydr. Polym.
2007, 69, 378; J. Kadokawa, M. Murakami, Y. Kaneko,
Compos. Sci. Technol. 2008, 68, 493; A. Takegawa, M.
Murakami, Y. Kaneko, J. Kadokawa, Polym. Compos. 2009,
30, 1837; K. Prasad, S. Mine, Y. Kaneko, J. Kadokawa, Polym.
Bull. 2010, 64, 341; J. Kadokawa, in Ionic Liquids, Application
and Perspectives, ed. by A. Kokorin, InTech, Rijeka, 2011, pp.
95–114; J. Kadokawa, J. Biobased Mater. Bioenergy 2013, 7, 3.
9)K. Prasad, J. Kadokawa, Polym. Compos. 2010, 31, 799; J.
Kadokawa, T. Kato, M. Setoyama, K. Yamamoto, J. Polym.
Environ. 2013, 21, 512.
10)A. Paul, P. K. Mandal, A. Samanta, Chem. Phys. Lett. 2005,
402, 375; A. Paul, P. K. Mandal, A. Samanta, J. Phys. Chem.
B 2005, 109, 9148; P. K. Mandal, A. Paul, A. Samanta, J.
Photochem. Photobiol. A: Chem. 2006, 182, 113; A. Paul, A.
Samanta, J. Chem. Sci. 2006, 118, 335.
11)S. Wakizono, K. Yamamoto, J. Kadokawa, J. Photochem.
Photobiol. A: Chem. 2011, 222, 283.
12)A. Miyawaki, J. Llopis, R. Heim, J. M. McCaffery, J. A.
Adams, M. Ikura, R. Y. Tsien, Nature 1997, 388, 882; J. R.
Lakowicz, in Principle of Fluorescence Spectroscopy 2nd
Edn., Plenum, New York, 1999.
13)H. Izawa, S. Wakizono, J. Kadokawa, Chem.Commun. 2010,
46, 6359.
14)S. Wakizono, K. Yamamoto, J. Kadokawa, J. Mater. Chem.
2012, 22, 10619; J. Kadokawa, in Ionic Liquids, New Aspects
for the Future, ed. by J. Kadokawa, InTech, Rijeka, 2013, pp.
653– 672.
15)Stępień, D. Bogdał, Czasopismo Techniczne. Chemia 2004,
101, 141; D. Bogdał, I. Stępień, J. Santera, E. Gondek,
Polimery 2003, 48, 111.
Introduction of the author :
Jun-ichi Kadokawa
Professor of Department of Chemistry, Biotechnology, and Chemical Engineering, Graduate School of Science
and Engineering, Kagoshima University, Japan
Jun-ichi Kadokawa was born in Matsuyama in 1964. He studied applied chemistry and materials chemistry
at Tohoku University, where he received his Ph.D. in 1992. He then joined Yamagata University as a Research
Associate. From 1996 to 1997, he worked as a visiting scientist at the Max-Planck-Institute for Polymer
Research in Germany. In 1999, he became an Associate Professor at Yamagata University and moved to Tohoku
University in 2002. He was appointed as a Professor of Kagoshima University in 2004. His research interests
focus on new functional polymeric materials using ionic liquids. He received the Award for Encouragement of
Research in Polymer Science (1997) and the Cellulose Society of Japan Award (2009).
6
No.159
Chemistry Chat
-Focusing on the Elements-
Naturally Occurring Organic Fluorine Compounds
Kentaro Sato
Valuable Fluorinated Compounds
One of the major trends in recent organic reaction
development is the introduction of fluorine atom. Because
fluorine is the most electronegative element of all elements,
the overall property of a given molecule can be changed to
great extent by introducing fluorine atom(s). The atomic
radius of fluorine is similar to that of hydrogen at the
same time, so the size of the molecule is not affected as
much. Due to these properties, the number of compounds
containing fluorine is increasing in pharmaceutical drugs
and organic electronics materials and so is the demand for
effective fluorination reactions.
CF3
N
F
N
N
N
NH2 O
F
F
An example of fluorine containing drug, sitagliptin (antidiabetic
drug)
Of course, fluorine containing compounds are found
in familiar areas outside of chemistry labs. Teflon ® is
not only the essential material for laboratory equipment
but is also used as non-stick coatings of kitchenware.
Chlorofluorocarbons (CFCs) were once used as refrigerants,
but its manufacture has been banned after the destructive
reactivity of CFCs against the ozone layer became widely
recognized. Today, less harmful alternatives of CFCs
(hydrochlorofluorocarbons or HCFCs) are used instead.
Fluorine containing compounds such as these are all
very useful, but in nature fluorine occurs in the form of
inorganic minerals like fluorite (CaF2) and cryolite (Na3AlF6)
and fluorinated organic compounds are extremely rare. C-F
bonds have strength and some unique properties, but Mother
Nature doesn’t seem to have utilized them so much. Still,
there have been about 30 natural products discovered that
contain C-F bonds. In this article, let us take a glance at
these naturally occurring fluorine containing compounds.
Deadly Poison-Monofluoroacetic Acid
The most famous naturally existing organic fluorine
containing compound is probably monofluoroacetic acid
(FCH2CO2H). This compound is found in a South African
plant called “Gifblaar,” which is known to be so poisonous
that ingesting only a half of its leaf is enough to kill a
cow. The compound is regulated as one of the “specified
poisonous substances” in Japan and it is illegal to own
or give it without permission. Let us be careful not to
synthesize it by mistake.
Acetic acid is an important biological substance, so it
may sound strange that structurally close monofluoroacetic
acid has such high toxicity. But in fact, that resemblance
is the very reason why it is so toxic. As mentioned
before, fluorine is about as large as hydrogen, therefore
monofluoroacetic acid can enter the citric acid cycle by
camouflaging acetic acid and inhibits the cycle, inducing the
toxicity.
Some other plants belonging to the Dichapetalaceae
family that includes Gifblaar synthesize fatty acids with a
fluorine atom attached on its end of the alkyl chain. The
7
No.159
from monofluoroacetaldehyde or monofluoroacetic acid are
likely to be discovered in the future.
examples such as ω-fluorostearic acid and ω-fluorooleic
acid are known. These are considered to be biosynthesized
when monofluoroacetic acid is taken into the regular fatty
acid biosynthetic pathway. These ω-fluoro fatty acids are
metabolized in the body to produce monofluoroacetic acid,
therefore show strong toxicity too and are the cause of many
known cases of animal food poisoning.
OH
O
F
OH
NH2
Fluorothreonine
O
More Examples of Fluorine-Containing
Natural Products
OH
F
Many marine natural products containing bromines
or chlorines are known, but those containing C-F bonds
are much rarer. The rarity is considered likely due to the
low concentration of fluorine in sea water and the fact
that fluorine doesn’t participate in biosynthesis as cationic
species unlike bromine. However, in 2003 a Chinese
research group discovered fluorine-containing compounds
from the extract of a marine sponge called Phakellia
fusca. The news drew attentions especially because the
compounds turned out to be structural analogues of
5-fluorouracil, which is a famous anti-cancer drug. These
compounds are again considered to be biosynthesized from
monofluoroacetaldehyde.
ω-Fluorooleic acid
Biosynthesis of Fluorine-Containing Natural
Products
Then how is monofluoroacetic acid biosynthesized?
One of the strains of actinomycete bacteria produces
monofluoroacetic acid and its biosynthetic pathway has
been elucidated. In this case, S-adenosylmethionine (SAM)
is converted into 5′-fluoro-5′-deoxyadenosine (5′-FDA) by
the action of the fluorinase enzyme. 5′-FDA is then thought
to decompose to form monofluoroacetaldehyde and get
oxidized to monofluoroacetic acid.
The fluorinase is an exceptionally unique enzyme
capable of catalyzing the formation of C-F bonds. There
is therefore an expectation that it can be developed into a
useful tool for synthesizing fluorine containing compounds.
O
O
OMe
5-FU derivative from marine sponge
OH
H2N
O
H2N
NH2
S+
O
N
F-
N
F
O
N
N
fluorinase
SAM
HO
N
N
N
N
HO
OH
OH
O
[O]
O
F
OH
F
H
Biosynthetic pathway of monofluoroacetic acid
8
N
O
A compound called fluorothreonine is also known,
and its biosynthetic origin is again considered to be
monofluoroacetaldehyde. More compounds biosynthesized
H3C
F
HN
5'-FDA
No.159
As another example, a natural fluorine-containing
compound called nucleocidin is known. This compound
has antimicrobial property through the inhibition of protein
synthesis. Its structure is unique in that the 4-position of the
ribose unit is fluorinated, which makes you wonder about its
biosynthetic pathway.
H2N
H2N
S
O
N
N
O
O
O
N
N
F
HO
OH
Nucleocidin
Natural or Unnatural?
In addition to these, some unexpected compounds
have been found in nature. Carbon tetrafluoride,
tetrafluoroethylene (the raw material of Teflon ®), and
trichlorotrifluoroethane (F2ClC-CFCl2 or Freon 113), all
of which you would never expect to exist naturally, are
among the examples. These compounds are not spillovers
from artificial source, but they are actually thought to exist
naturally. However, they are not biosynthesized by living
organisms but are believed to be formed from the reactions
between fluorine-containing volcanic gases and organic
compounds under high temperature conditions. There
are quite a few instances in which compounds that were
previously thought of as purely manmade turns out to also
exist in nature, and this one makes a perfect example.
Also worth mentioning is that trifluoroacetic acid is
sometimes detected in rainwater at certain concentrations.
The concentrations are suggested to be too high to be
explained as being originated from artificial sources. The
question of where it came from is yet to be answered.
Natural Elemental Fluorine
In 2012, the amazing discovery of elemental fluorine
gas (F2) in nature was reported. Fluorine gas is known to be
extremely reactive and reacts with even noble metals like
platinum and noble gases like xenon. The news that it can
exist in nature was therefore completely unexpected.
The elemental fluorine was discovered from mineral
rocks called antozonite. The rock is a type of fluorite (CaF2)
that contains radioactive uranium and it had been wellknown that it releases a pungent smell when you crush the
rock. It was named antozonite because the origin of the
smell was initially believed to be “anti-ozone,” which meant
the cation of oxygen speculated to exist in the rocks.
The research group of the Technical University of
Munich analyzed antozonite using 19F-NMR and was able to
prove the existence of molecular fluorine embedded within
the rocks. Because antozonite is mainly made of calcium
fluoride as mentioned earlier, the rocks can contain the
fluorine gas within itself without reacting with it.
But where did the fluorine gas come from in the first
place? According to the German group, the key to answering
the question is apparently in the radioactive uranium
contained in antozonite. The nuclear decay of uranium
gives off daughter nuclides and some of them emit beta and
gamma rays. Therefore, the group is proposing that the slow
nuclear irradiation of calcium fluoride over the period of
millions of years caused the formation of elemental fluorine
inside the rocks.
The existence of elemental fluorine in nature seemed
farfetched at first, but it is much more plausible now thanks
to this research. This story is a great reminder to us about
the remarkable depth of the natural world, and it also tells
us about the importance of believing in your research and
departing from conventional wisdom.
Introduction of the author :
Kentaro Sato
[Brief career history] He was born in Ibaraki, Japan, in 1970. 1995 M. Sc. Graduate School of Science and
Engineering, Tokyo Institute of Technology. 1995-2007 Researcher in a pharmaceutical company. 2007Present Freelance science writer. 2009-2012 Project assinstant professor of the graduate school of Science,
the University of Tokyo.
[Specialty] Organic chemistry
[Website] The Museum of Organic Chemistry <http://www.org-chem.org/yuuki/MOC.html>
9
No.159
Chemistry Chat
-Visit to a School Science Lab-
Visit to a Science Club
Science Club at Rikkyo Ikebukuro Junior & Senior High School (Part 2)
Introduction
In our previous issue, we gave a report about the club activities and recent study achievements of the science club of
Rikkyo Ikebukuro Junior & Senior High School. On this occasion, let us focus on what the students study. We were just
fully amazed to see their capabilities such as a self-constructed spectroscope, research collaboration with universities and
overcoming the limited environment of a high school laboratory. Please note that this report is about the students of academic
year 2012.
Mr. Goto, teacher/advisor, has TCI’s popular ballpoint pen in
his hand. Students are looking at a scroll paper hidden inside
with much interest.
Experiment by the club members. (From the left, Mr. Soejima
and Mr. Arima, former captain.) Both are attending a science
university since this April.
On the right, a whiteboard is placed for sharing member’s
schedules.
Award-winning studies of Japan Science & Engineering Challenge (JSEC2012)
T. Soejima (12th grade), Crystal growth control of MOF-5 with coordination modulation (Honor award).
This is a study that examines the synthesis of MOF-5, a metal organic frameworks (or porous coordination polymers),
from terephthalic acid and zinc with crystal growth controlled by adding benzoic acid. For the analysis and observation
of MOF-5, PXRD (Powder X-Ray Diffractometer, with the assistance of Professor Oyama, Rkkyo University) and SEM
(Scanning Electron Microscope, with the assistance of Professor Kasuga, Tokyo Metropolitan University, and Dr. Qiang Xu,
AIST) are used.
Y. Takahashi (11th grade), Consideration of phthalocyanine synthesis by Wyler’s method (Honorable mention
award).
This is a study that performs the Wyler’s method for phthalocyanine synthesis under aqueous conditions at room
temperature, which is environmentally-friendly and suitable for experiments at a high school laboratory. What is surprising is
that Mr. Takahashi made a self-constructed spectroscope from a store-bought single layer DVD, utilizing the diffraction and
interference phenomenon of its reflective surface.
10
No.159
Cell
Light
Slit
Spectrum
Figure Outline drawing of the DVD spectroscope.
He constructed the DVD spectroscope by reference to an article1), and performed this visible spectroscopic analysis by
processing the obtained spectral data of phthalocyanine with image analysis software. The line density of diffraction on a
DVD surface is about 1350 lines/mm. Thus, a DVD can be used as a high-resolution spectroscope inexpensively. We are very
much impressed with his creative attempt even to an analyzing tool in this way.
1) F . Wakabayashi, K. Hamada, J. Chem. Educ. 2006, 83, 56. http://dx.doi.org/10.1021/ed083p56
Award-winning studies of Japan Student Science Award Tokyo round (High school category)
H. Arima (12th grade), Alteration of a complex based on differences of cations (Grand Award).
This is a study that examines a change of solution color and crystal structure of Fe(III) ion complex [Fe(C2O4)3]3 through
alteration of co-existing cations (alkali metals, group 2 elements, transition elements and main group elements). Mr. Arima
considers crystal systems and causal factors based on X-ray crystal structural analysis (with the assistance of Professor
Morimoto, Rikkyo University).
K. Ohira (12th grade), Depolymerization of PET resin without metal catalyst (Incentive Award).
This is a study that aims to reproduce the depolymerization of PET (Polyethylene terephthalate) with a metal-free catalyst
and short heating time, suitable for experiments at a high school laboratory. It is expected that this study can lead to an
effective application of PET recycling.
Award-winning studies of Japan Student Science Award Tokyo round (Junior high school
category)
Y. Koike (8th grade), S. Hirai (8th grade), Creation of a fine copper mirror (Grand Award).
A fine copper mirror is produced on an inner wall of a test tube by reducing Fehling’s solution. This study examines
conditions to form a fine copper mirror by varying amounts of silver nitrate water solution, tin(II) chloride water solution,
Fehling’s solution A/ B and formaldehyde as reducing agent. Reactions with other reducing agents are also performed.
Y. Tsujimoto (7th grade), S. Nagata (7th grade), Staining of vinylon (Incentive Award).
Vinylon is synthesized by an acid-catalyzed reaction of polyvinyl alcohol with formaldehyde. Vinylon has high-strength,
high modulus, and also has high resistance to heat, weather and chemicals. But on the other hand, it has limited usefulness
due to the difficulty of dyeing it. In this study, he tries to dye it with BTB and litmus solutions.
Other studies performed in 2012
T. Kuramochi (7th grade), T. Okura (8th grade), Making bronze.
This study observes the luster and color of bronze by regulating the amounts of copper and tin.
N. Masaki (8th grade), Study of azo compounds.
In this study, he synthesizes azobenzene, and monitors the light-induced (355 nm) cis-trans isomerization of its azo group
as changing data on a spectrometry chart.
11
No.159
T. Uraki (9th grade), Observation of the surface temperature of rocks.
This study examines a mutual relationship between surface temperature and water absorption value using light-irradiated
water-retentive rocks. This result can be applied to external wall materials of buildings, and is expected to reduce energy
consumption.
T. Matsumoto (9th grade), Variation of the clock reaction under various conditions.
The clock reaction demonstrates the appearance of products after a period of time from the mixing of reactants. This
study analyzes the relationship between concentration and the reaction rate of various reagents, focusing on the iodine-starch
reaction as an example of the clock reaction.
T. Matsumoto (9th grade), Study of the influencing factors of a copper electrolysis reaction.
In this study, he examines the influence of the changes of the concentration of a copper (II) sulfate aqueous solution and
the voltage in the electrolysis reaction. Next, he has a plan for electrolysis reactions using complex ions.
Y. Nishio (10th grade), Effects on the forming of alumite by various negative plates.
Forming of alumite (anodic oxide) layers with high corrosion resistance is achieved by giving pretreatment to an
aluminum plate with steel wool. This study also demonstrates that alumite layers on a negative plate are rapidly formed when
zinc is used as the negative plate instead of aluminum.
R. Maruyama (11th grade), Making of non-woven fabrics by nylon.
Mr. Maruyama synthesizes 6,6-nylon with his self-produced winder and makes it into non-woven fabrics. He also
analyzes the difference in the making and strength of non-woven fabric by using various binders during the production
process.
S. Motohashi (11th grade), Study of chromic molecules with pH indicators.
The chromic molecule is a compound that changes its visible absorption spectrum by external stimuli. This study
measures the changes of the absorption spectrum of pH indicators (phenolphthalein and bromothymol blue) as chromic
molecules, using a self-constructed DVD spectroscope as described above.
Closing Remarks
We visited the school again on April 12, 2013 after the entrance ceremony was held, and saw students performing
demonstration experiments to welcome new students. The scene was just representing the start of a new school year. In May,
they installed a new experiment facility with a local exhaust ventilation system on each table. Also in July, they plan to attend
the “Cambridge Science Workshop” at the University of Cambridge to interact with cutting-edge researchers and British high
school students as a part of international exchange experience through science. We wish them continued success and further
growth in their activities.
We have given a series of two reports about the science club activities of Rikkyo Ikebukuro Junior & Senior High School.
We have great hopes in young and aspiring future researchers. We will continue to give you other reports and introductions
on science clubs in junior and senior high school.
Demonstration experiments are performed to welcome new
students (hydrogen generation experiment).
12
A local exhaust ventilation system is placed in the new
experiment laboratory. A fume hood is on the back. Electronic
balances and spectroscopes will be placed on the left table.
No.159
More ways to use reagents
Synthesis of Multi-substituted Olefins via SCOOPY Reaction
Haruhiko Taguchi
Tokyo Chemical Industry, Co. Ltd.
In this column, we focus on another usage of reagents from the viewpoint of the reagent company. In this
issue, we introduce a certain name reaction with its research progress.
Name reactions are very important synthetic methods in organic synthesis because their discoveries
have developed the progress of organic chemistry. I think young chemists study hard to develop novel and
innovative reactions and to be used as a name reaction in the future. Similarly, named reagents are available
from reagent companies. For chemists, it would be great honor to have their developed compound as a
named reagent. In this way, name reactions and named reagents motivate them to study hard day and night.
On the other hand, examples such as metathesis reaction and malonic ester synthesis, the names of
which are derived from the concept of each reaction, are also categorized as name reactions though they
aren’t people’s names. I think “name reaction” is a useful term since various types of organic reactions can be
expressed by a suitable single phrase.
Now, we are easily able to get the information about name reactions through the internet and a book titled
“STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS”, which has been published
and 250 named reactions are explained in detail. This book is good for study of organic reactions. When I
read it, I remembered a certain name reaction.
The name of this reaction is the SCOOPY reaction. I’m sure if you are fully aware of organic chemistry, you
will well know that reaction. I searched for the SCOOPY reaction using the internet but I could collect only little
related information. It seems that a chemically similar reaction named the Wittig-Schlosser reaction attracts
chemists more compared with the SCOOPY reaction. Due to that reason, the SCOOPY reaction would be not
widely known. However, the SCOOPY reaction has an advantage in the synthesis of trisubstituted olefins with
high stereoselectively.
By the way SCOOPY, who are you? SCOOPY says “I’m not a man, not a people’s name. I’m an
abbreviated word!”. “α-Substitution plus Carbonyl Olefination via β-Oxido Phosphorus Ylides”, which is
abbreviated to S.C.O.O.P.Y.1) This word is named by Prof. M. Schlosser, a developer of the Wittig-Schlosser
reaction. We can understand the concept of S.C.O.O.P.Y. from the above sentence as following, “to achieve
both α-substitution and carbonylolefination utilizing the chemical property of β-oxido phosphorus ylides”. Well,
what chemical properties do β-oxido phosphorus ylides have?
β-Oxido phosphorus ylides are generally formed by the further reaction of betains as intermediates of the
Wittig reaction with one equivalent of phenyl lithium. Initially, the erythro form of β-oxido phosphorus ylide is
kinetically formed as the main intermediate and then it is rapidly transformed to the more stable threo form,
because the rate of isomerization between them is sufficiently fast under low temperature.
O
X
Ph3PCH2R'
X
PhLi
Ph3PCHR'
Li
R C H
H
R' C
C
Ph3P
O
H
R
betaine
LiX
PhLi
Li
R'
C
C
Ph3P
O
H
R
LiX
R'
Li
C
C
H
R
Ph3P
erythro
β-Oxido Phosphorus Ylide
O
LiX
threo
more stable
13
No.159
M. Schlosser and his coworker have discovered the above-mentioned chemical properties of β-oxido
phosphorus ylides and applied them for novel organic synthesis. They have reported disubstituted olefins are
stereospecifically given by the treatment of the threo form of β-oxido phosphorus ylide with tert-butanol. This
synthetic manner is later named as the Wittig-Schlosser reaction.
Li
R'
SCOOPY Reaction
α-Substitution plus Carbonyl Olefination
via β-Oxido Phosphorus Ylides
R'
E
C
C
Ph3P
O
H
R
Ph3P O
C
Ph3P
O
erythro
R'
Li
E+
LiX
E = alkyl, aldehyde,
halide, etc.
C
C
C
Ph3P
O
H
R
Wittig-Schlosser Reaction
LiX
H
R
t
R'
H
C
C
Ph3P
O
LiX
LiX
Ph3P O
β-Oxido Phosphorus Ylide
H
R'
C C
E
H
R
threo
more stable
H
R'
BuOH
C C
R
tri-Substituted E-alkene
H
R
di-Substituted E-alkene
Furthermore, they published the report titled “Carbonyl Olefination with α-Substitution” in the first issue of
“SYNTHESIS” in 1969.2) The phrase in the title “with α-Substitution” can be expressed in “with α-Substitution
of β-oxido phosphorus ylides”. In this report, they showed that β-oxido phosphorus ylides can be α-substituted
by methyl iodide to afford trisubstituted olefins stereoselectively.
This reaction is later called the SCOOPY reaction, but at that time no one had called this reaction such a
name. The concept of “Carbonyl Olefination with α-Substitution” attracted many chemists and some of whom
had studied on the reactivities of β-oxido phosphorus ylides with various electrophiles.
Then, in 1971, M. Schlosser and his coworker reported a paper including the phrase “S.C.O.O.P.Y” in its
title in the journal of “SYNTHESIS”.1) The opening sentence of it is magnificently written and we can feel their
interest and inspiration at that time even after over 40 years have passed.
The SCOOPY reaction has been often used to produce trisubsituted olefins in fine organic chemistry,
especially, synthetic chemistry of natural compounds. This reaction is very excellent but it is very difficult to
control the stereochemistry with 100% selectively and in some cases, given that the reaction products include
almost same equivalent of E : Z mixture.
It seems that the SCOOPY reaction is a minor name reaction in spite of that the chemical property of
β-oxido phosphorus ylides is very attractive due to the similar reaction named the Wittig-Schlosser reaction
is very famous name reaction. However, the SCOOPY reaction gives one effective tool to synthesize
trisubsituted olefins with high stereoselectivity. The process of the S.C.O.O.P.Y, which utilizes the chemical
property of phosphorus to develop novel organophosphorus chemistry is recommended to be used with these
two name reactions, the SCOOPY reaction and the Wittig-Schlosser reaction, for your organic synthesis.
References
1)M. Schlosser, F. K. Christmann, A. Piskala, D. Coffinet, Synthesis 1971, 29.
2) M. Schlosser, F. K. Christmann, Synthesis 1969, 38.
Related Compounds
P1200
P1429
14
Triphenylpropylphosphonium Bromide
Phenyllithium (ca. 16% in Butyl Ether, ca. 1.6mol/L)
25g,
500g
100mL
No.159
Novel Fluorescent Probe for
Visualizing and Detecting Trace Amounts of Cesium Particulates
C2806 Cesium Green (1)
50mg
O
O
O
O
NO2
O
OH
1
Cesium Green (1), which has been developed by Ariga et al., is a fluorescent probe for detectable trace
amounts of cesium particulates. 1 emits green fluorescence under UV irradiation when it coordinates the
cesium cation enabling the cesium cation to be detected. Usually, fluorescent detection of cesium particulates
occurs after preparation of an aqueous solution. However, in fluorescent detection using 1, cesium particulates
on the surface of solids are directly visualized without any pretreatment. In addition, detection resolution of 1 for
cesium particulates reaches the micrometer level which can be seen with the naked eye. Thus, 1 is effectively
used for measuring the diffusion and accumulation process of cesium particulates.
The complex structure and fluorescence property of Cesium Green (1) with
Cs+ under UV irradiation (365 nm).
Reference
T. Mori, M. Akamatsu, K. Okamoto, M. Sumita, Y. Tateyama, H. Sakai, J. P. Hill, M. Abe, K. Ariga, Sci. Technol. Adv. Mater.
2013, 14, 015002.
15
No.159
Heteroarenecarbonyl Cinchona Alkaloid Catalysts
D4305 N-(9-Deoxy-epi-cinchonin-9-yl)picolinamide (1a)
D4306 N-(9-Deoxy-epi-cinchonidin-9-yl)picolinamide (1b)
CH2
100mg
100mg
CH2
N
N
H
N
N
O
O
N
N
1a
1b
Et2Zn (2-30 mol%)
R
N PG
O
+
H
R
PG=4-OMe-2-picolinoyl
Entry
OPh
OPh
benzene, MS 5Å, rt
3
4
H
N
R
P
Yield (%)
ee (%)
1a (10)
12
81
99 (R,R)
1b (15)
12
81
97 (S,S)
N PG
1a (15)
1b (20)
24
24
78
85
97 (R,R)
96 (S,S)
N PG
1a (10)
1b (15)
10
8
90
80
99 (R,R)
97 (S,S)
Me
Me
R
O
(1.5 eq.)
N PG
2
5
6
P
Ligand 1 (2-30 mol%)
Na2CO3 (1.5 eq.)
Aziridine
1
N
H
N
Ligand (mol%) Time
1)
PG
OPh
OPh
Nakamura et al. have developed the heteroarenecarbonyl cinchona alkaloid catalysts 1, and reported
the enantioselective desymmetrization of aziridines with phosphites using 1.1) According to their results,
various aziridines are converted into optically active b-aminophosphonic acids in high yields with high
enantioselectivities by using 1 and Et 2Zn as catalysts. In this approach, both enantiomers are directly
synthesized by using either 1a and 1b. Obtained optically active b-aminophosphonic acids and their derivatives
can be used as biologically active substances and chiral ligands.
Nakamura et al. have also reported the cinchona alkaloid amide/copper(II) catalyzed diastereo- and
enantioselective vinylogous Mannich reaction of ketimines.2) This article has been chosen as a "Hot Paper" by
the editors of "Angewandte Chemie" for its importance.
Typical Procedure: Enantioselective desymmetrization of aziridines with phosphites (Entry 1)
MS 5Å (100 mg) and Na2CO3 (32 mg, 0.30 mmol) are heated with heat-gun, and it is heated at 140 °C
under reduced pressure for 1 h. To a suspension of 1a (8.0 mg, 0.02 mmol), MS 5Å and Na2CO3 in benzene
(1.0 mL) is added Et2Zn (1.0 M in toluene, 20 μL, 0.02 mmol) and stirred for 10 min. A solution of aziridines
(0.20 mmol) and diphenyl phosphite (58 μL, 0.30 mmol) in benzene (0.5 mL) is added to the reaction mixture
and is stirred for 12 h. Then the reaction mixture is diluted with AcOEt and filtered through a celite pad. The
volatile compounds are removed under reduced pressure and the crude product is purified by silica gel column
chromatography (Hexane:AcOEt = 1:1) to give the desired (R,R)-product. The (S,S)-product is obtained by
using 1b instead of 1a.
References
1) C
inchona alkaloid amides/dialkylzinc catalyzed enantioselective desymmetrization of aziridines with phosphites
M. Hayashi, N. Shiomi, Y. Funahashi, S. Nakamura, J. Am. Chem. Soc. 2012, 134, 19366.
2) Cinchona alkaloid amide/copper(II) catalyzed diastereo- and enantioselective vinylogous Mannich reaction of ketimines
with siloxyfurans
M. Hayashi, M. Sano, Y. Funahashi, S. Nakamura, Angew. Chem. Int. Ed. 2013, 52, 5557.
16
No.159
Sparteines as Chiral Ligands for Asymmetric Synthesis
S0461 (−)-Sparteine (1)
S0884 (+)-Sparteine (2)
1g
1g
H
N
N
N
H
H
H
N
2
1
2)
N
N
N
s-Bu Li
HS
O
R
HR
HR
R
O
O
R
HR
O
s-BuLi / 1
N
EIX
O
fast
N
HS O
N
Li
retention
O
major
El
R S OCby
>95% ee
N
O
HR
El = Electrophile
O
kS / kR = 50 : 1
Cby =
O
N
O
N
N
s-Bu Li
HR
O
HS
R
O
N
N
Li
slow
HS
N
O
EIX
O
R
O
minor
retention
R El
HS R OCby
N
O
The alkaloid (−)-sparteine (1) has found widespread use as a chiral ligand for asymmetric reactions.1) The
complex formed from 1 and organolithium has recognized enantiotopic sides in its carbanions and prochiral
reaction partner’s protons.2,3) Asymmetric aldol additions using 1 and TiCl4 have provided aldol products
with excellent chiral selectivities.4) Palladium-catalyzed oxidation and the following resolutions of secondary
alcohols assisted by 1 as a ligand have provided the optically active alcohols.5) In addition, 1 has been used for
enantiomer-selective polymerizations.6)
(+)-Sparteine (2) is not easily obtained from natural source compared with 1. However, 2 has potential for a
chiral ligand which affords the products having an opposite configuration to those obtained by using 1.3)
References
1)
2)
3)
4)
5)
6)
eview of (−)-sparteine as a chiral ligand for metal catalysts
R
O. Chuzel, O. Riant, Top. Organomet. Chem. 2005, 15, 59.
Review of enantioselective synthesis with Li/(−)-sparteine carbanion pairs
D. Hoppe, T. Hense, Angew. Chem. Int. Ed. Engl. 1997, 36, 2282.
Asymmetric lithiation of (−)-sparteine and (+)-sparteine
H. Helmke, D. Hoppe, Synlett 1995, 978.
Asymmetric aldol additions using (−)-sparteine and TiCl4
M. T. Crimmins, B. W. King, E. A. Tabet, K. Chaudhary, J. Org. Chem. 2001, 66 , 894.
Palladium-catalyzed oxidative kinetic resolutions of secondary alcohols with (−)-sparteine
a) E. M. Ferreira, B. M. Stoltz, J. Am. Chem. Soc. 2001, 123, 7725.
b) M. S. Sigman, D. R. Jensen, Acc. Chem. Res. 2006, 39, 221.
Enantiomer-selective polymerizations using (−)-sparteine
Y. Okamoto, J. Polym. Sci. Part A: Polym. Chem. 2004, 42, 4480.
17
No.159
Fluoresceins for Fluorescent Labeling
F0026
F0783
F0784
C2477
C2478
C2479
F0810
A0306
A0864
Fluorescein 5-Isothiocyanate (isomer I) (= 5-FITC) (1)
Fluorescein 6-Isothiocyanate (isomer II) (= 6-FITC) (2)
Fluorescein Isothiocyanate (mixture of 5- and 6- isomers) (3)
5-Carboxyfluorescein Hydrate (= 5-FAM) (4)
6-Carboxyfluorescein Hydrate (= 6-FAM) (5)
5-Carboxyfluorescein N-Succinimidyl Ester (6)
Fluorescein-5-maleimide (7)
5-Aminofluorescein (isomer I) (8)
6-Aminofluorescein (isomer II) (9)
HO
O
OH
O
HO
O
OH
O
. xH2O
3
O
O
O
O
HO
OH
O
2
O
HO
O
SCN
O
1
HO
HO
O
SCN
O
SCN
OH
100mg, 1g
100mg
100mg, 1g
100mg
100mg
20mg, 100mg
25mg
1g, 5g
1g, 5g
OH
HO
O
O
O
HO
O
OH
. xH2O
O
N
O
O
O
O
O
5
4
HO
O
OH
HO
O
O
O
O
N
6
OH
O
HO
O
O
H2 N
O
H2N
OH
O
O
7
8
9
Fluorescein has been well-known as a green-fluorescent substance with the maximum absorption
wavelength (494 nm) and the maximum fluorescence wavelength (521 nm). 1, 2 and 3 containing an
isothiocyanate group can react and bond to an amino goup or a thiol group, so they are applied to the
fluorescent labeling of enzymes, antibodies and peptides.1) By using 4 and 5 which have a carboxyl group,
amino moieties such as the N-terminal of peptides are able to be labeled.2) 6 is a N-substituted succinimide of
4, the carboxyl moiety of which reacts readily with an amino group under mild conditions. It has been reported
that intracellular proteins are fluorescent-labeled by 6 when introduced into a cell. 3) 7 containing a maleimide
group can easily bond to the thiol group of cysteine residue etc.4) 8 and 9 can react with carboxyl moieties to
form amide bonding in the presence of a condensation agent.5)
References
1)a) H. Rinderknecht, Nature 1962, 193, 167. b) K. Muramoto, H. Meguro, K. Tuzimura, Agric. Biol. Chem. 1977, 41, 2059.
2)a) S. Onoue, B. Liu, Y. Nemoto, M. Hirose, T. Yajima, Anal. Sci. 2006, 22, 1531. b) P. Theisen, C. McCullum, K.
Upadhya, K. Jacobson, H. Vu, A. Andrus, Tetrahedron Lett. 1992, 33, 5033.
3)a) P. Breeuwer, J. Drocourt, F. M. Rombouts, T. Abee, Appl. Environ. Microbiol. 1996, 62,178. b) D. A. Fulcher, S. W. J.
Wong, Immunol. Cell Biol. 1999, 77, 559.
4)T. Cihlar, E. S. Ho, Anal. Biochem. 2000, 283, 49.
5)W. B. Dandliker, A. N. Hicks, S. A. Levison, R. J. Brawn, Biochem. Biophys. Res. Commun. 1977, 74, 538.
18
No.159
Bone Resorption Inhibitor
D4167 Disodium Tiludronate (1)
25mg
Cl
O
NH2
HO P ONa
Cl
O S O
O
O P C P O P O
H
O
O
O
S CH
HO P ONa
O
1
2
N
N
N
N
O
OH OH
Bisphosphonates (BPs), including alendronate, ibandronate, etc., are very effective inhibitors of bone
resorption in vivo and in vitro. Disodium tiludronate (1) is one of the BPs. These compounds are characterized
by two C-P bonds which are located on the same carbon atom, i.e. geminal BPs, and have been used in many
research projects regarding bone metabolism.
According to differences in the side chain, BPs can be divided into two groups, non-nitrogen containing
BPs and nitrogen-containing BPs. The former can be metabolized to methylene-containing analogues of
ATP (AppCp) and the metabolite causes osteoclast cell death. The latter can inhibit farnesyl pyrophosphate
synthetase in the mevalonate biosynthetic pathway. 1 is a non-nitrogen containing BP and compound 2 is the
AppCp from 1. For detailed information, please refer to the following references.1-5)
References
1)H. Fleisch, Endocr. Rev. 1998, 19, 80.
2) R. Graham, G. Russell, Ann. N.Y. Acad. Sci. 2006, 1068, 367.
3) R. Graham, G. Russell, Pediatrics 2007, 119, S150.
4) K. Ohno, K. Mori, M. Orita, M. Takeuchi, Cur. Medic. Chem. 2011, 18, 220.
5) M. J. Rogers, J. C. Crockett, F. P. Coxon, J. Mönkkönen, Bone 2011, 49, 34.
Surfactant for Biochemistry
L0254 Lithium Dodecyl Sulfate (1)
5g, 25g
O
CH3(CH2)11O S OLi
O
1
Sodium dodecyl sulfate (SDS) is a detergent used in life science research. Especially, SDS is frequently
used for polyacrylamide gel electrophoresis (PAGE). However, as SDS precipitates at low temperature,
improved methods by substitution of another cation for Na+ have been demonstrated to increase the solubility
of dodecyl sulfate. The method using lithium dodecyl sulfate (LDS, 1) is one of them and 1 is suitable for
electrophoresis at low temperature and low pH.1-3) Similarly, 1 has used for isolation of viruses, membrane
proteins, etc.4-6)
References
1) R. Lichtner, H. U. Wolf, Biochem. J. 1979, 181, 759.
2)P. Delepelaire, N.-H. Chua, Proc. Natl. Acad. Sci. USA 1979, 76, 111.
3) G. D. Jones, M. T. Wilson, V. M. Darley-Usmar, Biochem. J. 1981, 193, 1013.
4) M. C. Croxson, A. R. Bellamy, Appl. Environ. Microbiol. 1981, 41, 255.
5) E. Sugawara, H. Nikaido, J. Biol. Chem. 1992, 267, 2507.
6) S. G. Sawicki, D. L. Sawicki, J. Virol. 1990, 64, 1050.
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