METHODS FOR DECOLORIZING COMPOSITIONS COMPRISING BETAINES
The invention relates to a process for decolorizing a composition comprising a
betaine. The invention also relates to uses of polar solid decolorants for decolorizing
solutions, and to compositions obtainable by the inventive process.
Background of the invention
Betaines are neutral chemical compounds with a positively charged cationic
functional group, usually a quaternary ammonium or phosphonium group, and a
negatively charged functional group, usually as a carboxylate group. A betaine is
thus a zwitterion. Historically, the term "betaine" referred only to the specific
compound N,N,N-trimethylglycine.
Many betaines are vitamins, pharmaceuticals or precursors thereof. They are used
as food additives, diet components or pharmaceuticals. An important betaine is
carnitine (vitamin Bt; 3-hydroxy-4-(trimethylammonio)butanoate). Carnitine is a
quaternary ammonium compound biosynthesized from the amino acids lysine and
methionine. Carnitine exists in two stereoisomers. The biologically active form is Lcarnitine
(levocarnitine, LC), whilst its enantiomer, D-carnitine, is biologically inactive.
L-carnitine is an endogenous compound, which plays a key metabolic role,
transporting long chain fatty acids into the mitochondria for energetic oxidation.
Supplementation with acetyl-L-carnitine (ALC) has been shown to increase overall
regional cerebral metabolism in rodents. Carnitine and its esters also have nonmetabolic
roles in brain function as neuroprotectants, antioxidants and modulators of
neurotransmission.
Betaines, such as carnitine, are usually produced by organic synthesis at an
industrial scale. Typically, solutions of betaines in solvents, for example in aqueous
solution or in ethanol, are obtained. The solutions and solid products are subjected to
purification steps for obtaining the betaine at high purity, thereby removing salts,
solvent, residual starting products, side products and the like. Common purification
steps comprise crystallization, recrystallization, washing of crystallized products,
distillation, filtration and salt removal by ion exchange chromatography. As a result,
highly concentrated betaines are obtained in solid form.
Typically, solid betaines, such as carnitine, are colorless and solutions thereof are
likewise colorless and transparent. However, when such betaines are produced by
organic synthesis, and even when purified thereafter, often colorized products are
obtained. For example, carnitine produced by organic synthesis usually has a brown
or yellow coloration. The reason for the coloration is not precisely known.
Methods in the art for producing carnitine usually comprise a decoloration step,
wherein a solution comprising the carnitine product is contacted with activated
carbon. Activated carbon (active carbon, activated charcoal, activated coal) is a nonpolar
adsorbent capable of binding large amounts of non-polar substances due to its
high internal surface. After sufficient incubation time, a colorless solution is obtained,
whilst compounds causing the coloration are absorbed by the carbon. Betaines are
not bound to the activated carbon and thus decolorized. For example, the problem of
colorized carnitine products and decoloration with activated carbon are disclosed in
WO2007/003425 A2 (page 2, lines 14 to 22), US 2009/0325246 (section [0100]) or
EP 2 360 141 A 1 (section [0039]).
In the state of the art, ion exchange chromatography is applied for desalting aqueous
solutions of compositions comprising L-carnitine and converting L-carnitine salts into
the inner salt. CN1 01337902 A discloses a method for purifying L-carnitine from
aqueous solutions, in which pre-desalting steps are carried out with electroosmosis
and an anion exchange material, where after a decoloring treatment is carried out
with activated carbon.
CN1 0 187561 6 discloses another method for producing L-carnitine, wherein a
desalting step is carried out with an ion exchange material.
Decolorization of betaine solutions with activated carbon has certain drawbacks. At
first, activated carbon is relatively costly, especially when used in a large-scale
industrial process. Columns, which are packed with activated carbon, cannot be
recycled efficiently. The efficiency of decoloration is not always sufficient and
relatively large amounts of activated carbon are required for quantitative decoloration.
Trace amounts of carbon may remain in the product and may interfere with
subsequent reactions or uses, for example when subsequent reactions are carried
out with sensitive catalysts.
Moreover, decolorization with activated carbon, although efficient in aqueous
solutions, is not efficient in some organic solvents, such as ethanol. However,
synthesis of betaines in ethanol is an important industrial process. Thus there is a
need for efficient decoloring of betaines directly in such solutions in organic solvents.
WO96/15274 relates to methods for decolorizing aqueous solutions in the sugar
industry, which comprise high amounts of sugars and may comprise additional
A/,/V,/V-trimethylammonioacetat ("betaine"). The inventors suggest decoloration of the
sugar solutions with polyaluminium chlorides.
DE 1 136 7 11 relates to methods for extracting A/,/V,/V-trimethylammonioacetat
("betaine") from natural products, such as sugar rich juices and molasses. The
process is carried out with aqueous sugar-rich solutions and requires several
consecutive ion exchange treatment steps with cation and anion exchange resins.
DE 196 34 640 A 1 relates to methods for desalting aqueous solutions comprising
precursors for the production of L-carnitine. The method comprises at least
electrodialysis and cation exchange chromatography. The method does not relate to
decoloration of the solutions. Further, it is relatively complicated and requires long
treatment times of about 8 to 12 days.
It would be desirable to provide a process for decoloring betaines and betaine
solutions, especially carnitine and carnitine solutions, which overcome the above
mentioned problems. Specifically, it would be desirable to provide a process which
does not require a decoloration treatment with activated carbon, and which is also
efficient in organic solvents.
Problem underlying the invention
The problem underlying the invention is to provide processes, uses and decolorized
compositions, which overcome the above-mentioned problems. Specifically, the
problem underlying the invention is to provide a method for decolorizing betaines,
especially carnitine, without a decoloration step with carbon. The inventive process
shall allow effective decolorization of compositions and solutions whilst being
relatively simple, and being efficient in the presence of organic solvents. Chemicals
and devices required for the decolorization shall be easily available at low costs and
applicable for industrial large scale purification processes. The decolorization shall be
applicable within a relatively short time. Specifically, it shall be applicable for
solutions of purified betaines obtained in organic synthesis processes, for example
for solutions of L-carnitine in alcohols.
Disclosure of the invention
Surprisingly, the problem underlying the invention is solved by the processes, uses
and compositions according to the claims. Further inventive embodiments are
disclosed throughout the description.
Subject of the invention is a process for decolorizing a composition comprising a
betaine comprising the steps of
(a) providing a solution of the composition in an organic solvent,
(b) contacting the solution with a decolorant, wherein the decolorant is a polar
solid decolorant.
The inventive process is also a process for producing a decolorized composition
comprising a betaine. Decolorization of a composition can be monitored by known
methods, preferably by determining the transparency of the solution. In the inventive
process, the coloration of a colorized or at least slightly colorized starting solution, for
example a brown or yellow solution, is reduced or eliminated. Preferably, the product
solution obtained thereby is colorless, as solid betaine obtained from such a solution
after solvent removal. The invention relates to any process, in which the transparency
of the solution is increased and colorization is decreased.
Pure betaine solutions, such as L-carnitine solutions, should be colourless since the
betaines are colourless. However, such solutions tend to have undesired coloration,
often yellow or brown. This is especially a problem with betaine solutions and
betaines, which are a product of a preceding organic synthesis. Colorization seems
to be conferred to betaines and betaine solutions by impurities. However, it is not
known precisely which impurities colorize betaine solution. Such impurities seem to
be removed during the inventive process with a polar solid decolorant. This was
unexpected, because in the art non-polar activated carbon is used for decolorization.
In a preferred embodiment of the invention, the process comprises a subsequent
step of
(c) maintaining the solution for a time period sufficient for decoloring the solution.
In principle, a time period is considered sufficient, in which a desired degree of
decolorization is achieved. Preferably, the time period is of sufficient length to obtain
a fully decolorized, transparent solution. Preferably, the transparency of the solution
after step (c) is more than 70%, more preferably more than 80%, most preferably
more than 90% or more than 95%. Transparency is preferably determined at 430 nm
in a 50 mm cuvette. The betaine solution may be a standard solution of 0% (w/w)
betaine in the respective solvent, such as ethanol. Typically, the time period for
decoloration may be between 5 minutes and 20 hours, preferably between 20
minutes and 8 hours or between 30 minutes and 4 hours. Preferably, the
transparency of a betaine solution is increased at least by 10%, more preferably at
least by 20% or by 50%, preferably when carrying out the inventive process with 5
wt.% solid decolorant for 30 min. Specifically, this increase of transparency may be
observed for the solution obtained after step (b), after step (c) or after step (d), when
compared to the starting solution provided in step (a).
In a preferred embodiment, in step (c) the solution is moved mechanically, for
example by stirring, shaking or swaying. When keeping the solution in motion,
intimate contact of the ion exchange material with the solution is supported, thereby
increasing decolorization speed. When carrying out the process in a column, the
running speed is adapted such that the average contact time is sufficient.
In a preferred embodiment of the invention, the process comprises a subsequent
step
(d) separating the polar solid decolorant from the solution.
Preferably, the polar solid decolorant is removed by mechanical separation, for
example by sedimentation, filtration and/or centrifugation. Alternatively, the solid may
be removed within a device, such as a sieve, which is withdrawn from the solution
after a sufficient time period for decoloration.
In a preferred embodiment, the polar solid decolorant is provided in a column and the
solution is passed through the column. The column dimensions and running
conditions, such as column length and flow, are adapted such that the eluate is
decolorized sufficiently. Decoloration may be improved by using two or more columns
in series.
In the inventive process, the betaine does not bind, or essentially does not bind to the
solid decolorant. In contrast, typical betaine impurities seem to be bound to the polar
solid decolorant and are removed together with the solid decolorant from the solution,
where after a decolorized solution is obtained. According to the invention, the overall
process may comprise introduction of the polar solid decolorant into the solution,
incubation for a sufficient time to reach decoloration and separation of the solid
decolorant from the solution. Additional steps used in column purification processes
in the art, such as binding of betaines and elution with specific buffers, are not
required.
In a preferred embodiment of the invention, the solid decolorant is recycled.
Recycling can be carried out by treating the material with washing solution.
Appropriate washing solutions could have a high salt concentration and/or comprise
additives, such as detergents, for eluting impurities and recovery.
In a preferred embodiment of the invention, the process comprises after step (d) a
subsequent step of
(e) removing the solvent from the solution to obtain a solid decolorized
composition.
The solvent can be removed from the solution by methods known in the art, for
example by distillation. Preferably, the solvent is recycled, i . e. recovered and reused
in the process. In a specific embodiment, steps (b) to (e), or steps (b) to (d), are
carried out in consecutive order without additional purification steps in between these
steps.
After removal of the solvent, a solid decolorized composition is obtained. The
composition comprises, or essentially consists of, the betaines. It may be subjected
to additional purification steps, for example for removing residual solvent or residual
solid decolorant. For example, the solid composition may be dried, recrystallized, and
the like. In another preferred embodiment of the invention, the product, which is the
solid dry composition, is processed further. It may be processed into a desired
constitution, size and shape. For example, it may be converted into a powder,
granulate or tablets, optionally in a mixture with other components, such as
processing aids and/or vitamins.
The inventive process may be a batch process or continuous process. In a
continuous process, the solution passes the polar solid decolorant continuously.
As used herein, the term "betaine" refers to a generic group of chemical compounds.
A betaine is a neutral chemical compound with a single cationic quaternary functional
group, preferably a quaternary ammonium or phosphonium group, and a single
anionic functional group, such as a carboxylate group. The anionic and cationic
charge is permanent. Thus the cationic group does not comprise an acidic hydrogen
atom attached to the N or P atom. The betaine is thus a zwitterion. Preferably, the
betaine comprises a single quaternary ammonium group and a single quaternary
carboxylate group. The generic term "betaine" comprises, but does not specifically
refer to the specific compound N,N,N-trimethylglycine.
Preferably, the betaine used according to the invention is an inner salt. It does not
comprise, or essentially does not comprise an additional anion, such as chloride, or
an additional cation, such as H+ or ammonium. Carboxyl groups are essentially in the
ionic form. However, a minor portion, for example below 2%, below 0.5% or below
0.2% (w/w) may be in the acidic form.
According to the invention, the betaine is preferably not a polymer. In other words, it
is not product of a polymerization process from repetitive monomer units. It is
preferably a low molecular weight substance. Preferably, the molecular weight is
below 500, below 400 or below 300 g/mol.
In a preferred embodiment, the betaine is an ester, the betaine comprising a single
hydroxyl group which is esterified, preferably with an alkyl group having 1 to 20
carbon atoms, more preferably between 1 and 6 carbon atoms.
In a preferred embodiment of the invention, the betaine is a compound of formula (I):
R R2R3N+-X-COO , wherein
R , R2 and R3 are alkyl groups having 1 to 6 carbon atoms, which are selected
independently from each other, and
X is an alkandiyl group having 1 to 6 carbon atoms, which is linear or branched,
which is preferably methandiyl, ,2-ethandiyl or ,3-propandiyl,
the alkandiyl group being optionally substituted, preferably with a residue
selected from -OH, -NH2, -SH, -O-NHR 4 and -O-COR 4, wherein R4 is
preferably an alkyl group having 1 to 20 carbon atoms, which may be linear or
branched, more preferably methyl, ethyl, n-propyl, isopentyl or n-dodecyl.
Preferably, R , R2 and/or R3 is methyl and/or ethyl. Preferably, R R2R3N+- is a
trimethylammonium group. Preferably, the betaine is optically active.
In highly preferred embodiments of the invention, the betaine is L-carnitine, N,N,N-
trimethylglycine or an acylated L-carnitine. Preferably, the acylated L-carnitine is an
ester of L-carnitine and a carbonic acid having 1 to 20 carbon atoms, which is
preferably not branched. Preferably, the acylated L-carnitine is acetyl-L-carnitine
(ALC), propionyl-L-carnitine (PLC), isovaleryl-L-carnitine or lauroyl-L-carnitine.
In a preferred embodiment, the composition provided in step (a) essentially consists
of the betaine. However, relatively small amounts of impurities may be present, which
confer coloration to the composition and to the solution, in which the composition is
dissolved. In a preferred embodiment, the composition is a direct or intermediate
product from organic synthesis of the betaine, possibly with subsequent purification
steps. Preferably, it is already substantially free from salts, side products, starting
products and the like. Preferably, salts were removed in a preceding desalting step.
The desalting step may comprise any common method, such as dialysis, osmosis,
ultrafiltration, nanofiltration, distillation, extraction, crystallization, microfiltration and
the like. Preferably, the desalting step comprised electrodialysis, as disclosed for
example by WO20 0/089095, especially as in examples 1 and 2 thereof.
In a preferred embodiment of the invention, the composition in step (a) comprises
more than 50,%, more than 75%, more than 95%, preferably more than 98%, more
than 99.5% or more than 99.8% (w/w) of the betaine, especially L-carnitine, based on
the total amount of all solid components. More preferably, the composition in step (a)
comprises more than 95% L-carnitine, based on the total amount of all solid
components. In a preferred embodiment of the invention, the composition in step (a)
comprises less than 1%, preferably less than 0.2% or less than 0.05% (w/w) of salts,
based on the total amount of all solid components. Specifically, such salts may be
chlorides, acetates or cyanides. In a specific embodiment, the solution was subjected
to a preceding desalting step.
In a preferred embodiment, the composition in step (a) is a product of an organic
synthesis reaction for producing the betaine, especially L-carnitine. More preferably,
the product is a crude reaction product, which has not been pre-purified, or which has
only been desalted before. Typically, such a reaction product comprises the betaine,
side products and residual unreacted starting materials. Often, such crude reaction
products have an undesired color. The side products and residual starting materials
are often structurally related to the betaine. Therefore, decolorization of such organic
reaction products is relatively difficult.
In a preferred embodiment, the betaine, such as the L-carnitine, is not a natural
product and/or not purified from a natural product. In other words, it is not extracted
from natural products, for example from sugar rich biological materials. Preferably,
the composition provided in step (a) does not comprise sugars, or less than 0.1 %
(w/w) or less than 1% (w/w) sugars, based on the overall solids.
Preferably, the solution provided in step (a) consists of the solid composition and the
organic solvent.
The solvent is an organic solvent, preferably a polar organic solvent, such as an
alcohol, ether or ester. In a highly preferred embodiment, the solvent is an aliphatic
alcohol, more preferably one comprising 1 to 6 carbon atoms, such as methanol,
ethanol, isopropanol or butanol. Most preferably, the solvent is ethanol. The solvent
may also be a mixture of organic solvents, for example a mixture of ethanol with
another organic solvent, for example one comprising up to 90% (w/w) or up to 50%
(w/w) ethanol. In a preferred embodiment of the invention, the solution in step (a)
comprises 5 to 75%, preferably 0 to 50%, more preferably 15 to 40% (w/w) of the
betaine composition, the rest being solvent.
Organic solvents, such as ethanol, may comprise low amounts of water. According to
the invention, the organic solvent, especially ethanol, may comprise low levels of
water, for example less than 5% (w/w), less than 1% (w/w), less than 0.5% (w/w) or
less than 0.1 % (w/w). In specific embodiments, the solvent is technical grade ethanol,
comprising between 2 and 4% (w/w) water, or absolute ethanol, comprising less than
1% (w/w) water, or even less than 0.1 % (w/w) water.
In a preferred embodiment, the organic solvent does not comprise water, or does
essentially not comprise water. The term "essentially" means that only inevitable
impurities of water may be present.
According to the invention, decolorization of the betaine solution is mediated by a
polar solid decolorant. As used herein, the term solid refers to room temperature
(23°C) and to a solid substance remaining after removal of all solvent. The solid
decolorant is not dissolved during the process. At least the surface of the decolorant
is polar. Polar substances have electric dipoles at the surface. Such solids are
hydrophilic. Preferably, the polar solid is capable of forming hydrogen bonds in
aqueous solution. Preferably, the polar solid comprises charged groups, more
preferably cationic groups, and/or oxygen atoms on the surface.
According to the invention, it was found that betaine solutions in organic solvents,
such as ethanol, are decolorized efficiently with polar solid decolorants. This was
unexpected, because according to the state of the art decoloration was carried out
with activated carbon, which is a non-polar adsorbent and thus tends to adsorb
hydrophobic substances. Further, activated carbon, although being efficient in water,
is considerably less efficient in decolorizing betaines in organic solvent, such as
ethanol (see examples).
In a preferred embodiment of the invention, the polar solid decolorant is an ion
exchange material. Typically, the surface of ion exchange materials comprises ionic
groups, Lewis acidic and/or Lewis basic groups. The ion exchange material may be
an anion exchange material, which is preferred, or a cation exchange material. It may
also be an amphoteric exchange material, which is capable of exchanging both
cations and anions. In addition, the ion exchange material may have adsorptive or
absorptive characteristics. Mineral based ion exchangers comprising silicates, such
as bentonite and Fuller's earth; or hydrotalcite, combine ion exchange properties with
adsorptive properties. According to the invention, it was found that with various ion
exchange materials, colorizing impurities can be removed efficiently from solutions
comprising betaines. However, it is not known whether all impurities are removed by
anion exchange interactions, or whether some impurities are also, or partly, removed
by absorption or adsorption. Such interactions tend to interact and thus a clear
distinction, although desirable in theory, is not always practically appropriate. Thus,
the invention is not restricted to specific binding mechanisms.
Unlike activated carbon, common ion exchange materials, such as polymeric ion
exchange resins or mineral-based silicates and hydrotalcite, are colorless. If at all,
they release only trace amounts of impurities into the solutions, mostly traces of salts,
which are usually acceptable for subsequent uses and applications. Thus, the use of
the polar solid decolorants is advantageous for preparing betaine solutions or
betaines.
In a preferred embodiment of the invention, the ion exchange material is an ion
exchange resin, a silicate or hydrotalcite. The process may also use combinations of
such ion exchange materials or combinations with other polar solid decolorant, or
apply multiple consecutive decoloring steps with different ion exchange materials.
In a preferred embodiment of the invention, the ion exchange material is an ion
exchange resin, more preferably an anion exchange resin. Such a resin is based on
an organic polymer matrix. Preferably, the resin comprises ionic groups. Preferably,
the ionic groups are positively charged. In a highly preferred embodiment, the groups
are quaternary ammonium groups. The ionic groups are covalently linked to the
matrix with appropriate spacers. Such anion exchange resins are known in the art
and commercially available, for example from Dow Chemical/Rohm and Haas, US,
under the trademark "Amberlite".
In another preferred embodiment, the ion exchange material is or comprises a
silicate. Silicates comprise silicate groups, but may comprise also other inorganic
groups, atoms and ions. Typically, silicate ion exchange materials are minerals or
derived from minerals. In a preferred embodiment of the invention, the mineral is or
comprises bentonite, montmorillonite and talc, or is derived from such a mineral.
Such minerals are known in the art and commercially available. Bentonite is based
on aluminium silicate, which comprises montmorillonite. Talc is a hydrated
magnesium silicate. Montmorillonite is a hydrated sodium calcium aluminium
magnesium silicate hydroxide. In a preferred embodiment, the silicate comprises
magnesium. Preferably, the mineral is Fuller 's earth. Silicate-based ion exchange
materials useful in the inventive process are commercially available, for example
from Sud-Chemie, DE, under the trademarks "Tonsil" or EXM 607. In a preferred
embodiment, the pH of the silicate, especially the bentonite, when dissolved in water,
is above 5, more preferably about 5 to 9 .
Bentonites are known and available with variations in composition and properties.
According to the invention, it was found that decoloration of betaines is efficient in
organic solvents with various bentonites. However, especially good results were
obtained when using a bentonite comprising about 65 to 75% S1O2, about 8 to 12%
AI2O3, about 3 to 5% MgO and about 2 to 4% Fe2O3 (all percentages are weight %).
Preferably, this bentonite has a pH above 5, such as between 5 and 9, when
dissolved in water. Such a bentonite is available under the trademark EXM 607 from
Sud-Chemie, DE.
In another preferred embodiment, the ion exchange material is or comprises
hydrotalcite. Hydrotalcite is a layered double hydroxide of general formula
(Mg6Al2(CO3)(OH)i6 -4(H2O). Hydrotalcite has anion exchange capabilities. It is
commercially available, for example under the trademark Sorbacid 9 1 from Sud-
Chemie, DE. In a preferred embodiment, the pH of the hydrotalcite, when suspended
in water, is above 7, more preferably about 7 to 11.
Hydrotalcites are known and available with variations in composition and properties.
According to the invention, it was found that decoloration of betaines is efficient in
organic solvents with various hydrotalcites. However, especially good results were
obtained when using a hydrotalcite comprising about 5 to 25% AI2O3 and about 30
to 40% MgO (all percentages are weight %). Preferably, this hydrotalcite has a pH
above 7, more preferably about 7 to 11, when suspended in water. Such a preferred
hydrotalcite is available under the trademark Syntal HAS 696 from Sud-Chemie, DE.
Methods are known in the art for increasing the ion exchange capability and also
absorptive properties of such minerals. The ion exchange capability can be increased
by chemical treatments. In a preferred embodiment of the invention, the mineral is
pre-activated by an acid treatment. Acid treatments, also referred to as "acid
activation", affect the outer and inner surfaces and acidity of such minerals, yielding
products with a specific pore structure and a specific distribution of cationic and
anionic groups on the surface. Fuller's earth is obtained by acidic activation of
minerals, usually from bentonite. It is used in the art for purifying oils and lipids.
In another preferred embodiment of the invention, the polar solid decolorant is or
comprises an alkaline earth metal oxide. The alkaline earth metal oxide may consist
of the alkali metal and oxygen, or may comprise other metal cations and anions. It
may also comprise other components, such as crystal water. Preferably, the alkaline
earth metal oxide is magnesium oxide or calcium oxide. Surprisingly, a very effective
and rapid decoloration was observed in the presence of magnesium oxide. This is
advantageous, because magnesium oxide is colorless and inexpensive.
In a preferred embodiment of the invention, the polar solid decolorant is an inorganic
material, such as a mineral, such as a silicate or hydrotalcite, or an alkali metal oxide.
In the inventive process, a decoloration step with carbon, especially activated carbon,
is not necessary. Thus it is preferred that the overall process does not comprise a
use of molecular carbon or activated carbon for decolorization. In an embodiment of
the invention, the decolorant is not a polyaluminium chloride.
The polar solid decolorant may be provided in any appropriate form, such as a
powder, granules, pellets, a solid block and the like. Preferably, the solid decolorant
has a high internal surface area, and thus a high contact surface. Thus a fine powder
and/or a porous structure may be advantageous.
Subject of the invention is also the use of a polar solid decolorant, which is preferably
an ion exchange material and/or an alkaline earth metal oxide, for decolorizing a
composition comprising betaines, preferably L-carnitine. Subject of the invention is
also the use of a process of the invention for decolorizing a composition comprising
betaines, preferably L-carnitine.
Preferably, the inventive process is also a process for decolorizing betaines,
preferably L-carnitine, or for decolorizing solution comprising betaines, preferably Lcarnitine.
Another subject of the invention is a decolorized solution or composition, obtainable
by an inventive process. According to the invention, it is possible to obtain a
decolorized solution or composition of pure or substantially pure betaine or Lcarnitine.
The inventive solution or composition is distinct from typical decolorized
solutions or compositions of pure betaines or carnitine, because no residual traces of
activated carbon are comprised. This is advantageous for possible subsequent
reactions or uses, which could be impaired by traces of carbon, for example sensitive
reactions in the presence of catalysts.
The inventive process solves the problem underlying the invention. The invention
provides a simple and effective process for the decolorization of betaines, such as Lcarnitine,
which is effective also in the presence of organic solvent. A solution is
decolorized simply by contacting with a polar solid material, especially an ion
exchange material and/or an alkaline earth metal oxide. Mineral based ion exchange
materials, such as Fuller ' s earth, are easily available in large amounts and
significantly cheaper than activated carbon. Thus the use of such materials provides
a significant cost advantage in industrial large scale processes for the production of
betaines, compared to conventional processes using activated carbon. Activated
carbon used in the art for decolorizing betaines does not comprise ionic, acidic or
basic groups on the surface. Thus, it could not be assumed that efficient
decolorization could be achieved by simply contacting a solution of the betaine with
ion exchange material
Examples
General Methods
Transparency of L-carnitine solutions was determined at 430 nm in 50 mm cuvettes
and evaluated according to U.S. Pharmacopeia (USP) chapter 06 .
Examples 1 to 6 : decolorization with ion exchange materials
An L-carnitine solution was decolorized with various ion exchange materials in batch
processes. The L-carnitine was a crude product obtained by organic synthesis having
a brownish to yellowish coloration. An ethanolic L-carnitine solution was prepared
with 20.39% (w/w) L-carnitine concentration. Transparency was determined to be
20.3%. In a flask equipped with a magnetic stir bar and reflux condenser, 80 g of the
ethanolic L-carnitine solution and 6.25 wt.% of the ion exchange resin were charged.
The anion exchange resins used comprised a cross-linked polystyrene matrix with
quaternary ammonium groups (trademark Amberlite FPA90CI and FPA98CI; Dow
Chemical, US). The mixture was stirred for the given time at 60°C before the resin
was removed by filtration. Carnitine concentration and transparency of solutions
obtained thereby were measured. The conditions and results are summarized in
table 1 below.
Example Resin Time Cone. Transp.
[h] [% w/w] [%]
1 Amberlite FPA98CI 0.5 20.49 67.2
2 Amberlite FPA98CI 1.0 20.63 68.2
3 Amberlite FPA98CI 1.5 20.71 70.6
4 Amberlite FPA90CI 0.5 20.53 7 1.8
5 Amberlite FPA90CI 1.0 20.51 7 1.9
6 Amberlite FPA90CI 1.5 20.43 7 1.6
Table : conditions and results of examples 1 to 6
Example 7 : ion exchange chromatography
L-carnitine solution was decolorized in a continuous process by anion exchange
chromatography. A double jacket reactor (500 ml) was provided with an internal
stirrer. A double jacket column (diameter: 15 mm; length: 460 mm) was provided
underneath the reactor. The solution from the reactor was applied to the column inlet
at the head of the column through a connection. A collecting vessel was positioned
underneath the column outlet for collecting the eluate. A thermostat each kept the
temperature in the reactor and in column at 60°C. The anion exchange resin
comprised a cross-linked polystyrene matrix with quaternary ammonium groups
(trademark Amberlite FPA 90CI; Dow Chemical, US). The resin was pre-treated by
washing with 2000 ml deionized water followed by washing with 500 ml anhydrous
ethanol. 50 g fresh resin was filled into the double jacket column and washed with the
given washing solutions, where after the column was warmed up to 60°C. The Lcarnitine
used was a crude product obtained by organic synthesis having a brownish
to yellowish coloration. A feed solution of L-carnitine in ethanol was filled into a
reactor, heated to 60°C and applied with an average flow rate of 6-7 g/min to the
column. A colorless eluate was collected. In total, 24 kg of carnitine in ethanol coming
from three batches (batch 1: 7.6 kg L-carnitine in ethanol, transparency = 64.3%;
batch 2 : 8.5 kg L-carnitine in ethanol, transparency = 8 1%; batch 3 : 7.8 kg L-carnitine
in ethanol, transparency = 63.8%) were treated as described. The yield after anion
exchange chromatography was 00%. A colorless solution (transparency >95%) was
obtained.
Examples 8 to 28
Further examples were carried out with various materials to assess their capability of
decoloring L-carnitine solutions. Solutions of L-carnitine were combined with various
solid materials and the colors of the solutions were monitored. Comparative
examples 8 and 9 were controls without decoloring materials. Examples 0 and 11
were comparative examples with activated carbon. Examples 12 to 19 were carried
out with various polar anion exchange materials. Comparative examples 20 to 22
were carried out with non-polar ion exchange or adsorbent materials. Example 23
was carried out with a cation exchange material. Examples 24 and 25 were carried
out with alkaline metal oxides. Comparative examples 26 to 28 were carried out with
other inorganic compounds. Solutions of L-carnitine in water (40% w/w) and ethanol
( 10-25% w/w) were prepared. The L-carnitine was a crude product obtained from
organic synthesis, having a brownish to yellowish coloration. The solution was heated
to 40°C. The initial transparency of the solutions was determined (430 nm, 50 mm
cuvette), and determined as <7% for EtOH and 4% in water. The decoloring
materials were added (3% w/w), mixed and kept at 40°C for two hours. After two
hours, the ion exchange material was removed by filtration and the transparency was
determined. The ion exchange materials, properties of the materials and results are
summarized in Table 2 below. The compositions and properties of the hydrotalcites
and bentonites are summarized in Table 3 below.
No decolorization was observed in the control experiments with water or ethanol
alone. Strong decolorization was observed with various polar materials, which are
anion exchange resins, silicates, hydrotalcite, magnesium oxide and calcium oxide.
In comparative examples, it was found that activated carbon is efficient in water, but
of low efficiency in ethanol. Also other materials with non-polar surfaces are not
efficient (examples 20 to 22).
Table 2: Ion exchange materials and results. Transp. = transparency; (C) = comparative example
Table 2: Compositions and properties of decolorants used in examples 12 to 17

CLAIMS
1. A process for decolorizing a composition comprising at least one betaine
comprising the steps
(a) providing a solution of the composition in an organic solvent,
(b) contacting the solution with a decolorant, wherein the decolorant is a
polar solid decolorant.
2 . The process of claim 1, comprising a subsequent step
(c) maintaining the solution for a time period sufficient for decoloring the
solution.
3 . The process of claim 1 or 2, comprising a subsequent step
(d) separating the solid decolorant from the solution.
4 . The process of claim 3, comprising a subsequent step
(e) removing the solvent from the solution to obtain the solid decolorized
composition.
5. The process of at least one of the preceding claims, wherein the solvent is
an alcohol, preferably ethanol.
6 . The process of at least one of the preceding claims, wherein the betaine is
a compound of formula R R2R3N+-X-COO , wherein
R , R2 and R3 are alkyl groups having 1 to 6 carbon atoms, which are
selected independently from each other, and
X is an alkandiyl group having 1 to 6 carbon atoms, which is linear or
branched,
the alkandiyl group being optionally substituted, preferably with a residue
selected from -OH, -NH2, -SH, -O-NHR 4 and -O-COR 4, wherein R4 is an
alkyl group having 1 to 20 carbon atoms.
7. The process of at least one of the preceding claims, wherein the betaine is
L-carnitine, N,N,N-trimethylglycine or acylated L-carnitine.
8. The process of at least one of the preceding claims, wherein the
composition in step (a) comprises more than 95%, preferably more than
98% or more than 99.5% (w/w) of the betaine, based on the total amount of
all solid components.
9. The process of at least one of the preceding claims, wherein the solution in
step (a) comprises 5 to 50% (w/w) of the composition.
10. The process of at least one of the preceding claims, wherein polar solid
decolorant is an ion exchange material and/or an alkaline earth metal oxide.
11.The process of claim 10, wherein the ion exchange material is an ion
exchange resin, a silicate or hydrotalcite, and/or wherein the alkaline earth
metal oxide is magnesium oxide or calcium oxide.
12. The process of a claim 11, wherein the ion exchange resin is an anion
exchange resin, which preferably comprises quaternary ammonium groups.
13. The process of claim 11, wherein the silicate is or comprises a mineral
selected from bentonite, montmorillonite, talc, or is derived from such a
mineral, preferably by pre-activation by acid treatment.
14. The process of at least one of the preceding claims, wherein the
composition in step (a) is a product of an organic synthesis reaction for
producing the betaine.
15. The process of at least one of the preceding claims, wherein the
transparency of the betaine solution is increased at last by 10%, when
compared to the transparency of the starting solution provided in step (a).
16.A decolorized solution or composition obtainable by a process of at least
one of the preceding claims.
17. Use of a polar solid decolorant for decolorizing a composition comprising
betaines in a process of at least one of claims 1 to 15.