U.S. patent application number 11/475825 was filed with the patent office on 2007-12-27 for process for converting primary amidoalcohols to amidocarboxylic acids in high yield.
This patent application is currently assigned to Conopco, Inc., d/b/a UNILEVER, Conopco, Inc., d/b/a UNILEVER. Invention is credited to Bijan Harichian, Vivek Subramanian.
Application Number | 20070299270 11/475825 |
Document ID | / |
Family ID | 38480636 |
Filed Date | 2007-12-27 |
United States Patent
Application |
20070299270 |
Kind Code |
A1 |
Harichian; Bijan ; et
al. |
December 27, 2007 |
PROCESS FOR CONVERTING PRIMARY AMIDOALCOHOLS TO AMIDOCARBOXYLIC
ACIDS IN HIGH YIELD
Abstract
The invention relates to an improved process for oxidizing a
primary amidoalcohol to the corresponding amidocarboxylic acid in
high yield.
Inventors: |
Harichian; Bijan;
(Brookfield, CT) ; Subramanian; Vivek; (Southbury,
CT) |
Correspondence
Address: |
UNILEVER INTELLECTUAL PROPERTY GROUP
700 SYLVAN AVENUE,, BLDG C2 SOUTH
ENGLEWOOD CLIFFS
NJ
07632-3100
US
|
Assignee: |
Conopco, Inc., d/b/a
UNILEVER
|
Family ID: |
38480636 |
Appl. No.: |
11/475825 |
Filed: |
June 27, 2006 |
Current U.S.
Class: |
554/63 ;
562/526 |
Current CPC
Class: |
C07C 231/12 20130101;
C07C 231/12 20130101; C07C 231/12 20130101; C07C 233/47 20130101;
C07C 233/49 20130101 |
Class at
Publication: |
554/63 ;
562/526 |
International
Class: |
C07C 237/02 20060101
C07C237/02 |
Claims
1. A process for converting an alcohol comprising amide group to
corresponding carboxylic acid in yield .gtoreq.75% which process
comprises reacting: R.sup.1--CONR.sup.2(CH.sub.2).sub.mOH wherein
R.sup.1 is linear or branched alkyl or alkenyl group having 7 to 22
carbon atoms; R.sup.2 is H, an alkyl or hydroxyalkyl group with 1
to 6 carbon atom(s); and m is an integer from 1 to 6, with an
oxidizing agent in the presence of a hindered nitroxide radical and
optional co-catalyst, wherein the solvent in which the reaction
takes place is selected such that, in the presence of the oxidizing
agent, the solvent layer separates from the aqueous layer, and the
amidoalcohol partitions into the organic liquid solvent layer to
thereby permit the high yields noted; wherein said solvent is
tetrahydrofuran.
2. A process according to claim 1, wherein the alcohol comprising
amide group is an alkanoylmonoalkanolamine.
3. A process according to claim 2, wherein the
alkanoylmonoalkanolamine is lauroyl monoalkanolamide or
cocomonoethanolamide.
4. A process according to claim 1, wherein the oxidizing agent is
selected from the group consisting of chlorine, a hypochlorite,
chloroisocyanuric acid, and mixtures thereof.
5. A process according to claim 1 wherein the oxidizing agent is
selected from the group consisting of NaOBr, bromosuccinimide,
bromoisocyanuric acid, peracids, oxone, H.sub.2O.sub.2 and mixture
thereof.
6. A process according to claim 1, wherein oxidizing agent is
present in amount from equimolar to 8 molar.
7. A process according to claim 1, wherein the nitroxide catalyst
is 4-acetamido-TEMPO.
8. A process according to claim 1, where, in addition to hindered
nitroxide radical co-catalyst is used.
9. A process according to claim 8, wherein co-catalyst is alkali
metal halide or alkali earth metal halide.
10. (canceled)
11. (canceled)
12. A process according to claim 1, wherein solvents contain
substantially no anti-oxidants.
13. A process according to claim 1 where base is additionally added
to the reaction.
14. A process according to claim 1 wherein sufficient base is added
to maintain pH above 6.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a process for converting a
compound or polymer comprising a primary alcohol and an amide group
to amidocarboxylic acid. In particular, the primary amido alcohol
is converted to carboxylic acid in unexpectedly high yields when
proper solvent is selected.
BACKGROUND
[0002] Amidocarboxylic acids are desirable surfactants in that they
have good water solubility, good detergency and foaming properties
and are mild to skin and hair. One method for the production of
such surfactant is through the oxidation of an alcohol containing
an amide group (e.g., coco mono-ethanolamide or CMEA).
[0003] The problem, however, is that it is very difficult to drive
the oxidation of alcohol to carboxylic acid efficiently. The
reaction will often stop at the aldehyde stage, and the yields of
carboxylic acid as final products are quite low.
[0004] Japanese Patent laid-Open No. 05/194,334 (Sandoz) discloses
a process in which a hydroxyl containing compound (which may be,
for example, alkyl amide polyoxyalkanol) is made to react with at
least an equimolar amount of inorganic or organic
halogen-containing oxidizing agent, e.g. NaOCl, in the presence of
weak base and a catalytic amount of hindered nitroxide as
exemplified by 2,2,6,6-tetramethylpiperidine 1-oxyl, hereafter
abbreviated TEMPO, and chemical derivatives thereof. In this
patent, no yield or purity information is given. The process
disclosed is limited to alcohols which have polyethylene glycol or
polypropylene glycol substitution, or to polyglucosides, as
starting reactants. Such compounds are water-soluble or
water-dispersible, which makes possible the use of water as the
solvent. The patent does not teach a process using hydrophobic
primary alcohols (i.e., amido alcohols) of the invention as
starting reactant.
[0005] Japanese Patent Laid Open No. 04/283,537 (Shell) discloses a
process using an oxidizing agent such as sodium hypochlorite in the
presence of TEMPO. The process relates to production of an
alkoxyalkanoic acid from the corresponding alkoxyalkanol, however,
and not to the production of an amidecarboxylic acid from an
alcohol having an amide group.
[0006] Japanese Laid Open No. 10/087,554 (Lion Corporation)
discloses a process for production of amidocarboxylic acid from
alcohol having an amide group using an oxidizing agent of chlorine
type (e.g. NaOCl) in the presence of a nitroxide radical (e.g.,
TEMPO) and further in the presence of alkali metal halide or alkali
earth metal halide (e.g., potassium chloride). In Examples 3 and 5,
for example, an alcohol comprising amide; a nitroxide radical; and
a 10% solution of alkali metal chloride (potassium or sodium
bromide) in water, additional water, and acetonitrile (solvent) are
charged into a beaker and stirred. Under these conditions, the
acetonitrile and water mix together to form a single liquid phase.
In each example, the purity of the carboxylic acid is calculated
from the acid value, but nothing is stated about yield. The acid
value is not selective for the desired carboxylic acid, but would
include all acid components present.
[0007] Unexpectedly, applicants have now found that the type of
solvent or solvents used during the oxidation reaction is critical
to the yield of product (carboxylic acid). Without wishing to be
bound by theory, applicants believe the starting amidoalcohol must
not be in the same phase as the oxidizing agent. Applicants have
found that this separation of oxidizing agent and alcohol can be
accomplished in at least two different ways. According to claims of
the subject application, the final product (e.g., amidocarboxylic
acid) is partitioned into an organic solvent (i.e., using solvent
that will form both a hydrophobic liquid phase and an aqueous
liquid phase, rather than forming one substantially aqueous phase).
In this manner, the exposed amide group on the amidoalcohol is
protected from cleavage (e.g., the bleach which has partitioned
mainly into aqueous phase will not attack the amidoalcohol in the
separate phase), and consequently far greater yield of
amidocarboxylic acid is produced. That is, it is important that, in
the presence of the oxidizing agent, both a solvent rich layer
(substantially free of oxidizing agent) and an aqueous layer
(comprising substantially of the oxidizing agent) form.
[0008] In a second embodiment, subject of applicant's copending
application, the oxidizing agent and the alcohol are also
maintained in separate phases. Here, however, the two phases are a
water phase and a solid phase, and water alone is used as the
solvent. That is, the amidoalcohol, which is hydrophobic, does not
dissolve or disperse into the aqueous phase (rather it stays in the
solid, non-aqueous phase) while the NaOCl remains in the continuous
aqueous phase.
[0009] As indicated, the subject application relates to processes
where a liquid organic solvent is employed and solvent(s) partition
into at least two liquid phases. In such circumstances, applicants
have further discovered that the type of solvent is a critical
parameter.
BRIEF DESCRIPTION OF THE INVENTION
[0010] The present invention provides a process for converting
primary alcohol having an amide group to amidocarboxylic acid in
high yield (e.g., .gtoreq.75, preferably .gtoreq.80%, more
preferably .gtoreq.85%, more preferably .gtoreq.90% yield) which
process comprises reacting a primary alcohol having amide group
(amidoalcohol) with an oxidizing agent, preferably a
chlorine-containing oxidant like NaOCl, in the presence of a
nitroxide radical and optionally in the presence of an alkali metal
halide or alkali earth metal halide. In this process the solvent in
which the reaction takes place is selected such that, in the
presence of the oxidizing agent, the primary amidoalcohol
partitions (after addition of bleach or other oxidizing agent) into
the liquid organic phase while bleach or oxidizing agent stays
substantially in liquid aqueous phase. Such partitioning ensues the
high yields noted above (e.g. because the amide linkage is not
available to be cleaved by the oxidizing agent which has
partitioned into liquid aqueous phase). In other words, the
amidoalcohol partitions quickly enough into the organic phase to
avoid formation of undesired by-product. It is completely
unexpected that the specific type of solvent chosen could make such
critical difference.
[0011] It is also a critical aspect of the invention that the
catalyst used in this reaction be a hindered nitroxide radical. An
optional alkali metal halide or alkali earth metal halide
co-catalyst may also to be used, or the co-catalyst can be, for
example, sodium tetraborate.
[0012] Specifically, in one embodiment of the invention, sufficient
base (e.g., sodium hydroxide) is added to the reaction to ensure
reaction takes place at a pH above 6, preferably 7 to 10, more
preferably 7.5 to 9, even more preferably 8 to 9. Addition of base
is used to make up for consumption of oxidizing agent (e.g., sodium
hypochlorite) during formation of amidocarboxylic acid. Base may be
added to the oxidizing agent solution prior to addition of the
oxidizing agent to the reaction or it may be added during the
course of the reaction (e.g., to maintain constant pH).
[0013] These and other aspects, features and advantages will become
apparent to those of ordinary skill in the art from a reading of
the following detailed description and the appended claims. For the
avoidance of doubt, any feature of one aspect of the present
invention may be utilized in any other aspect of the invention. It
is noted that the examples given in the description below are
intended to clarify the invention and are not intended to limit the
invention to those examples per se. Other than in the experimental
examples, or where otherwise indicated, all numbers expressing
quantities of ingredients or reaction conditions used herein are to
be understood as modified in all instances by the term "about".
Similarly, all percentages are weight/weight percentages of the
total composition unless otherwise indicated. Numerical ranges
expressed in the format "from x to y" are understood to include x
and y. When for a specific feature multiple preferred ranges are
described in the format "from x to y", it is understood that all
ranges combining the different endpoints are also contemplated.
Where the term "comprising" is used in the specification or claims,
it is not intended to exclude any terms, steps or features not
specifically recited. All temperatures are in degrees Celsius
(.degree. C.) unless specified otherwise. All measurements are in
SI units unless specified otherwise. All documents cited are--in
relevant part--incorporated herein by reference.
BRIEF DESCRIPTION OF THE DRAWING
[0014] FIG. 1 is a liquid chromatogram (HPLC) profile of products
formed when reaction was carried out in CH.sub.3CN/water solvent
and only a single liquid phase was formed (bottom figure,
corresponding to example of JP 10/087,554 reference to Lion),
compared to when solvent was THF/water and formed two liquid phases
(top).
[0015] As observed, a solvent which partitions into two liquid
phases leads to high yields of N-lauroylglycine (LG) from
N-lauroylmonoethanolamide (LMEA) starting material. By contrast,
when the organic solvent formed a single liquid phase with the
water, the yield and purity of LG (glycinide) were lower. Thus, for
example, the pure LG product was predominantly formed at 13.54
minutes when two liquid phases formed but, when only one phase
formed, there were huge amounts of impurities at 15.80 seconds.
DETAILED DESCRIPITON OF THE INVENTION
[0016] The present invention relates to a novel and improved
process for converting a primary alcohol comprising an amide group
(e.g., C.sub.8-C.sub.22 alkoylmonoalkanolamide such as lauroyl
monoethanolamide) to the corresponding amidocarboxylic acid (e.g.,
mixture of N-lauroyl glycine and alkalimetal N-lauroyl glycinate),
and which process provides very high yields of product (e.g.,
.gtoreq.75%, preferably .gtoreq.80%, more preferably .gtoreq.85%
yield). More specifically the process comprises reacting a primary
alcohol comprising such amide group with an oxidizing agent in the
presence of a nitroxide radical and optional catalyst (e.g., alkali
metal halide), wherein the solvent in which the reaction takes
place is selected in such way that two liquid phases separating the
amidoalcohol from the oxidizing agent are formed. In other words,
the amidoalcohol is partitioned into the liquid organic phase of
the two phase system thereby and the oxidizing agent stays
predominantly in the liquid aqueous phase. This protects the amide
group on the amidoalcohol from further cleavage and provides the
high yields as noted. In a second embodiment of the invention
(claimed in copending application), the amidoalcohol is separated
from the oxidizing agent using only water as solvent in that the
oxidizing agent partitions into the liquid aqueous phase while the
amidoalcohol stays in the undissolved solid state (heterogeneous
solid-liquid system).
[0017] More specifically, the starting reactant of the subject
invention is an alcohol having an amide group which may be defined
as follows:
R.sup.1--CONR.sup.2(CH.sub.2).sub.mOH
[0018] wherein R.sup.1 is linear or branched alkyl or alkenyl group
having 7 to 22 carbon atoms; R.sup.2 is H, an alkyl or hydroxyalkyl
group with 1 to 6 carbon atom(s); and m is an integer from 1 to
6.
[0019] Examples of compounds which may be encompassed by the
structure are N-alkanoylmonoethanolamines such as
N-lauroylmonoethanolamide (LMEA) or N-cocoylmonoethanolamide
(CMEA).
[0020] The starting product may be a mixture of monoalkanolamides
(e.g., monoethanolamine) including those derived from mixtures of
fatty acids found in nature. N-cocoyl monoethanolamine, for example
may comprise a mixture of C.sub.8, C.sub.10 and C.sub.12 fatty
acids as major component mixed with C.sub.14, C.sub.16 and C.sub.18
fatty acids.
[0021] The oxidizing agent used to oxidize the starting alcohol can
be any oxidizing agent which will allow the alcohol group to be
oxidized to carboxylic acid. Typically, such oxidizing agents
include those of the chlorine type. These may include chlorine, a
hypochlorite (e.g., alkali metal hypochlorite),
trichloroisocyanuric acid and dichloroisocyononic acid. Preferred
oxidizing agents include sodium hypochlorite (e.g., industrial
grade bleach comprises 5% to 13% sodium hypochlorite), calcium
hypochlorite, chlorine itself, and organic chlorine-containing
compounds, for example trichloroisocyanuric acid. Non-chlorine
containing oxidants may be used, for example, oxone (2
KHSO.sub.5.KHSO.sub.4.K.sub.2SO.sub.4), NaOBr, N-bromosuccinimide,
or tribromoisocyanuric acid. Non-halogen containing antioxidants
may also be used, as exemplified by H.sub.2O.sub.2, optionally in
the presence of sodium tungstate dihydrate catalyst.
[0022] The amount of oxidizing agent may vary, but typically
equimolar to 8 molar, preferably 1 to 7 equivalents, more
preferably 2 to 6 molar are used.
[0023] The starting alcohol of the invention is oxidized with an
oxidizing agent (as noted above) in the presence of a hindered
piperidinyloxy radical catalyst (nitroxide) and optionally in the
presence of co-catalyst as are described below.
[0024] The nitroxide catalyst radical used in the invention (e.g.,
hindered nitroxide) is produced by oxidation of a cyclic or acyclic
secondary amine containing no .alpha.-hydrogens (i.e., there are no
hydrogens on the carbon adjacent to N) with peroxide, or by
oxidation of the corresponding hydroxylamine. Examples of stable
nitroxide radicals suitable for use in this invention are mentioned
in the following documents. These include linear, cyclic, dicyclic
or macromolecular compounds to which one or more nitroxyl radicals
are connected. [0025] Chem. Review, 78, 37 (1979): [0026] G.
Rozantsev, "Free Nitroxyl Radicals", Penum Publishing Corporation,
New York, 1970; and [0027] E. G. Rozantsev, V. D., Scholle,
Synthesis, 1971, 190.
[0028] Preferred examples of the nitroxide radical are as follows.
[0029] 2,2,6,6-Tetramethyl-piperidine 1-oxyl (TEMPO); [0030]
2,2,5,5-Tetramethyl-pyrrolidine 1-oxyl; and [0031]
1-Aza-2,2,7,7-tetramethyl-cycloheptane 1-oxyl.
[0032] TEMPO and chemical derivatives thereof are preferred,
examples of which follow: [0033]
4-Hydroxyl-2,2,6,6-tetramethyl-piperidine 1-oxyl; [0034]
4-Methoxy-2,2,6,6-tetramethyl-piperidine 1-oxyl; [0035]
4-Ethoxy-2-2,6,6-tetramethyl-piperidine 1-oxyl; [0036]
4-Acetylamido-2-2,6,6-tetramethyl-piperidine 1-oxyl; [0037]
4-Carbamoyl-2,2,6,6-tetramethyl-piperidine 1-oxyl; [0038]
4-Benzoylamino-2,2,6,6-tetramethyl-piperidine 1-oxyl; [0039]
4-Oxo-2,2,6,6-tetramethyl-piperidine 1-oxyl; [0040]
2,2,6,6-Tetramethyl-piperidine-1-oxyl 4-sulfate; [0041]
2,2,6,6-Tetramethyl-piperidine-1-oxyl 4-phosphate; and [0042]
3-Carbamoyl-2,2,6,6-tetramethyl-pyrrol idine 1-oxyl.
[0043] UV light stabilizers containing
2,2,6,6-tetramethylpiperidine functionality (Hindered Amine Light
Stabilizers, abbreviated HALS), both monomeric and oligomeric, can
serve as precursors to stable nitroxyl radicals by oxidation as
well.
[0044] It is also possible that an amine or a hydroxylamine which
is a precursor thereof is used and, in the actual case, it is
oxidized and then used. The amount of the nitroxide radical used to
1 equivalent of the starting alcohol material is typically from
0.01 to 10 mol % or, preferably, from 0.1 to 5 mol % based on
amidoalcohol.
[0045] An optional co-catalyst is often used with the nitroxide
radical primary catalyst. The co-catalyst, if used, may be for
example an alkali metal halide or alkali earth metal halide. These
may include alkali metal bromide, e.g. sodium bromide, and alkali
metal chloride, e.g. sodium chloride, and potassium chloride,
alkali earth metal bromide, e.g calcium bromide and magnesium
bromide, alkali earth metal chloride, e.g. calcium chloride, and
magnesium chloride.
[0046] Typically the co-catalyst is used from 0.01 to 10 mole %,
preferably 0.1 to 5 mol % equivalent based on amidoalcohol. Sodium
tetraborate may be used in place of the bromide or chloride.
Solvent
[0047] The key to the invention resides in the selection of proper
solvent, i.e., solvent which will partition into liquid organic
phase and liquid aqueous phase upon combination of oxidizing agent
and amidoalcohol in the solvent.
[0048] Although the ideal solvents are at least partially water
miscible (e.g., tetrahydrofuran), the key is that, in the presence
of oxidizing agent (e.g., aqueous sodium hypochlorite), at least
two immiscible liquid layers (e.g., a solvent-rich layer, normally
the upper layer; and a water-rich layer, normally the lower layer)
will form.
[0049] Without wishing to be bound by theory, applicants believe it
is important that the amidoalcohol not be in the same phase as the
oxidizing agent when combined. Applicants have found that this can
be accomplished in two different ways. According to claims of the
subject invention, this can be done by partitioning the final
product (amidocarboxylic acid) into a liquid organic solvent (i.e.,
using solvent that will form two phases, rather than forming one
substantially aqueous phase). The exposed amide group on the
alcohol comprising amide is thus protected from cleavage (e.g.,
through attack by the bleach which has partitioned mainly into
separate liquid aqueous phase), and consequently far greater yield
of carboxylic is produced. That is, it is important that, in the
presence of the oxidizing agent, both a solvent rich layer
(substantially free of oxidizing agent) and an aqueous layer
(comprising substantially of the oxidizing agent) form. It should
be noted that how quickly the two phase separation occurs is
dependent generally on the scale of the reaction. Typically, the
phase separation will occur in an hour or less, and can occur
relatively instantaneously.
[0050] A second way to maintain the oxidizing agent and the alcohol
in separate phases, in this case in a liquid water phase and in a
solid phase, is to use water alone as the solvent. The amidoalcohol
is hydrophobic and does not dissolve or disperse into the aqueous
phase (it stays in solid phase), while the NaOCl remains in the
continuous liquid aqueous phase.
[0051] A reaction in which the solvent will form only one liquid
phase (e.g., CH.sub.3CN/water solvent used in JP 10/087,554), thus,
is not suitable and will form product in lower yield and
purity.
[0052] Surprisingly, solvents at opposite extremes of the polarity
scale may be suitable for the reaction. Suitable polar solvents may
include oxygenated hydrocarbons, more specifically cyclic and
acyclic ethers and polyethers. Suitable non-polar solvents may
include cyclic and acyclic aliphatic solvents, and aromatic
solvents.
[0053] Specific examples of cyclic oxygenated solvents (e.g. polar
solvents) which may be used include tetrahydrofuren (THF) and
dioxolane. Examples of acyclic oxygenated solvents include
1,2-dimethoxyethane, dimethoxymethane, diethoxymethane, and
2-methoxyethyl ether.
[0054] It is preferred that the solvents do not contain
anti-oxidants (e.g., butylated hydroxyl toluene, abbreviated as
BHT) as these anti-oxidants can interfere with the oxidation
reaction. Such anti-oxidants are often found in cyclic and acyclic
ethers and polyethers. Thus, preferably, solvents of the invention
are substantially anti-oxidant free.
[0055] Specific examples of cyclic aliphatic solvents (e.g.,
non-polar solvents) include cyclohexane; examples of acyclic
aliphatic solvents include heptanes and hexanes; and examples of
aromatic solvents include toluene, o, m, or p-xylene, and mixed
xylenes.
[0056] In preferred reaction, because of the consumption of
oxidizing agent (e.g., sodium hypochlorite) and formation of
carboxylic acid as consequence of the reaction, sufficient base
should be used in the reaction to maintain pH above 6, more
preferred above 7, preferably 8-9. An example of base which may be
used is alkali metal hydroxide (e.g., NaOH).
[0057] The base may be added to the oxidizing agent before the
oxidizing agent is added to the reaction or, alternatively, the
base may be added, for example, drop-wise during the course of the
reaction as needed to maintain constant pH.
[0058] The reaction itself typically takes place at room
temperature, but is exothermic. Temperature rises of up to about
35.degree. C. occur without cooling. A cooling bath can be used to
reduce the exotherm.
[0059] A typical example of an oxidation of a monoethanolamide
(N-lauroylmonoethanolamide, or LMEA) to N-lauroylglycine (LG), as
well as reaction conditions, isolation methology and rate of
conversion to LG are set forth below:
##STR00001## [0060] Reaction Conditions: [0061] Solvent:
Tetrahydrofuran (THF)/Water [0062] Oxidizing agent: NaOCl (bleach,
11.5%, 3 eq.)+NaOH (base to maintain pH) [0063] Catalyst: KBr
(co-catalyst), 4-Acetamido-TEMPO (abbreviated AA-TEMPO) [0064]
Reaction temp: 25-30.degree. C. [0065] pH range: 12 (initial) to 6
(final) [0066] Reaction time: 1-4 hr. [0067] Isolation: THF
extraction followed by solvent evaporation [0068] Typical
conversion rate: 95-99%
[0069] It should be noted that a mixture of N-lauroylglycine and
sodium N-laurylglycinate (e.g., salt form) can be obtained
depending on isolation pH and therefore, yields can be calculated
separately for each.
EXAMPLES
Protocol
Extraction Technique to Isolate Carboxylic Acid (e.g.,
N-laurylglycine)
[0070] At completion of oxidation reaction, reaction mixture is
acidified to pH about 3.0 (e.g., by addition of HCl) and layers are
separated. Lower aqueous layer is extracted with THF and the
combined THF layers are concentrated on a rotary evaporator and
dried in vacuo to give carboxylic acid (e.g., N-lauroylglycine) as
a white solid.
Extraction Technique to Isolate Alkali Metal or Alkaline Metal Salt
of Carboxylic Acid (e.g., Sodium N-Lauroylglycinate)
[0071] The reaction here is the same as above except THF layer is
separated without acidification. The aqueous layer must be in the
range of 6-10, preferably 6-8. The aqueous layer is extracted
(preferably twice) with THF. Combined THF layers are concentrated
on a rotary evaporator and dried in vacuo to yield the salt (e.g.,
N-lauroylglycinate)
Alternative Extraction Technique for the Carboxylic Acid
[0072] Besides THF extraction, carboxylic acid can be isolated by a
drowning procedure and filtration. In this procedure, the reaction
mixture is acidified to pH about 2-3 and added to excess of water
(about 3-4 volumes compared to reaction mixture volume) with
vigorous stirring using a stirring paddle. Precipitate is collected
by filtration, washed with water and dried in vacuo to give
carboxylic acid (e.g., N-alkanoyl-glycine).
Reaction Monitoring of Cocoyl MonoEthylAmide (CMEA) Oxidation to
Cocoyl Glycinate (CG) by HPLC
[0073] Instrument: Waters 2695 Separations Module equipped with a
Waters 2996 Photodiode Array Detector [0074] Software: Empower Pro
(version 5.00, Waters Corp.) [0075] Column: Restek Pinnacle DB C18
5 um, 4.6.times.150 mm maintained at 30.degree. C. [0076] Flow
Rate: 1 ml/min [0077] Sample: 1-2 mg/ml in 1:1 water:acetonitrile
(W:ACN) containing 0.04% acetic acid (AcOH) [0078] Injection Vol:
15 uL [0079] Mobile Phase: A=2 mM ammonium acetate, 0.04% AcOH
[0080] B=2 mM ammonium acetate, 0.04% AcOH 90% aqueous ACN [0081]
Gradient: 95:5 A:B to 100% B (gradient, 35 min) followed by 100% B
(isocratic, 5 min) [0082] Detection: 205 nm
Example 1
[0083] Oxidation of N-lauroylethanolamide (LMEA) in THF with 6.5
eq. of NaOCl, and Acid Work-up. 33 mg (4.5 mol %) of KBr
(co-catalyst) was dissolved in 6 mL of water. Tetrahydrofuran
solvent THF (31 mL), AA-TEMPO catalyst (25 mg, 2.5 mol %) and 1.5 g
N-lauroylethanolamide (LMEA) were added with stirring to give a
homogeneous water-white solution. Sodium hypochloride oxidizing
agent (22 mL of 11.5% aq. Solution, 6.5 equivalents) and 2.3 mL of
2 NaOH (to maintain pH above 7) were mixed. The combined solution
was added dropwise to the solution of LMEA and catalyst over a
period of 1.5 hour. A separate aqueous layer immediately formed
upon addition of the sodium hypochlorite solution. The pH of the
aqueous layer was 12.7 after addition of the first 3.5 ml. The
temperature was maintained below 32.degree. C. with an ice-water
bath. The reaction was stirred for 0.5 hr. more until complete
conversion of LMEA to LG as determined by reversed-phase High
Pressure Liquid Chromatography, abbreviated HPLC. The pH at end of
the reaction was 7.6.
[0084] At completion of the reaction, the mixture was acidified to
pH 3.0 (to get the purified carboxylic acid) by addition of 8.5 mL
of 1 N HCl, and the layers were separated. The lower aqueous layer
was extracted with 30 mL THF, and the combined THF layers were
concentrated on a rotary evaporator and dried in vacuo to give
N-lauroylglycine in 116% yield (residual water present).
Example 2
[0085] Oxidation of LMEA with 3.25 eq. of NaOCl, and Acid Work-up.
The procedure in Example 1 was followed, except that the amount of
sodium hypochlorite was decreased to 3.25 equivalents. The isolated
yield was 103% (includes residual water), showing that the
oxidation works with the lower sodium hypochlorite amount.
Example 3
[0086] Oxidation of LMEA with 3.25 eq. of NaOCl, Isolation of
Sodium Salt. In this example, sodium N-lauroylglycinate is obtained
by a small modification of the isolation procedure. The procedure
in Example 2 was followed. The pH was 7.8 upon completion of the
reaction. In this case the THF layer was separated without
acidification. The aq. layer was extracted twice with 30 mL of THF.
After extraction, the pH of the aq. layer was 8.3. The combined THF
layers were concentrated on a rotary evaporator and dried in vacuo
to give sodium N-lauroylglycinate in 99% yield. Unlike
N-lauroylglycine, the sodium N-lauroylglycinate dissolves in water
and affords a foam upon agitation.
Example 4
[0087] Oxidation of LMEA in THF with 6.5 eq. of NaOCl, Drowning
Procedure at pH=2.6. The procedure of Example 1 was followed except
for the isolation step. After completion of the reaction, the
mixture was acidified to pH=2.6 with 9.25 mL of 1 N HCl. The entire
reaction mixture (both THF and water phases) were poured in 240 mL
of water with vigorous stirring. The precipitated product was
isolated by gravity filtration, and washed with 200 mL water. After
air-drying, and further drying in vacuo, the product was obtained
in 77% yield. The yield can be improved by better filtration
techniques, e.g. by pressure filtration through a 0.45 .mu.m or
less filter.
Example 5
[0088] Oxidation of LMEA in THF with 3.25 eq. of NaOCl, Drowning
Procedure, Effect of pH on Yield. The procedure of Example 2 was
followed except for the isolation step. After completion of the
reaction, the mixture was only partially acidified (to pH=5.2 with
3.6 mL of 1 N HCl.) The entire reaction mixture (both THF and water
phases) were poured in 240 mL of water with vigorous stirring. The
precipitated product was isolated by gravity filtration, and washed
with 240 mL water. After drying in vacuo overnight, the product was
obtained in 59% yield (based on free carboxylic acid), and 55%
(based on the sodium carboxylate). The lower yield than Example 4
is attributed to the larger proportion of the water-soluble sodium
carboxylate at the higher pH.
Example 6
[0089] Oxidation of LMEA with 3.25 eq. of NaOCl in Water, Acid
Work-up. KBr (33 mg, 4.5 mol %) and M-TEMPO (25 mg, 2 mol %) were
dissolved in 50 mL water. 1.50 g LMEA was added and the mixture
stirred 1.5 hr. to form a homogeneous suspension. Dilute sodium
hypochlorite (5%) was added in 2.0 mL increments over 1.3 hr. After
each addition, 0.1 N HCl was added, if necessary to maintain a pH
of 8-9.
Details of the addition are given in the Table below:
TABLE-US-00001 5% NaOCl (mL) 0.1 N HCl pH 0.0 -- 6.5 2.0 3.4 8.6
4.0 1.8 8.5 6.0 1.1 8.5 8.0 0.6 8.5 10.0 1.0 8.5 12.0 0.4 8.5 14.0
-- 8.5 16.0 -- 8.2 18.0 -- 8.1 20.0 -- 8.0 22.0 -- 8.0 25.0 --
8.0
[0090] After stirring for 20.5 hr., the pH dropped to 5.9. The
mixture was a translucent white emulsion. It was brought to pH=3.0
by addition of 3.5 mL of 1 N HCl, and extracted twice with 75 mL of
THF. The combined THF layers were concentrated on a rotary
evaporator and further dried in vacuo to give 1.81 g of
N-lauroylglycine in 114% yield (includes residual water).
Example 7
[0091] Oxidation of N-Cocoylmonoethanolamide (CMEA) with 3.25 eq.
of NaOCl using Toluene as Solvent, Acid Work-up. The oxidation
reaction works on mixtures of monoethanolamides as well, including
those derived from mixtures of fatty acids occurring in nature. In
this example, N-cocoylmonoethanolamine (a mixture of C-8, C-10,
C-12 (major component), C-14, C-16, and C-18 monoethanolamides) was
oxidized under similar conditions to give a mixture of the
corresponding N-cocoylglycines. KBr (33 mg, 4.5 mol %) and AA-TEMPO
(25 mg, 2 mol %) were dissolved in 6 mL of water. CMEA (1.50 g,
6.16 mmol assuming 100% LG) was dissolved 60 mL toluene at
32.degree. C., and the solution added to the KBr and M-TEMPO. The
stirred mixture was maintained at 31-37.degree. C. during the
course of the addition and hold period. A solution of sodium
hypochlorite (11 mL of 11.5% aq. solution, 3.25 eq.) and 1.15 mL of
2 N NaOH was added in 2.0 mL increments over a period of 50 min.
The pH was 6.9 at the end of the addition. After 40 min. at
33.degree. C., the pH was adjusted to 8.6 with 0.5 mL of 1 N NaOH.
Stirring was continued for an additional 3.5 hr. and then the
solution was allowed to cool to room temperature.
[0092] The gelatinous reaction mixture was diluted with 70 mL THF
and brought to pH=2.2 with 5.5 mL of 1 N HCl. The layers were
separated, and the aq. layer were extracted with an additional 20
mL THF. The combined THF layers were concentrated on a rotary
evaporator and dried in vacuo to give of N-cocoylglycine in 84%
yield.
Example 8
[0093] Oxidation of N-Cocoylmonoethanolamide (CMEA) with 3.25 eq.
of NaOCl using Cyclohexane as Solvent, Acid Work-up. The procedure
of Example 4 was followed, except that the CMEA was dissolved in
120 mL cyclohexane at 43.degree. C. instead of toluene. After the
reaction a translucent emulsion (pH=6.2) was obtained. The emulsion
was brought to pH 3.1 with 3.0 mL of 1 N HCl, and extracted twice
with 100 mL THF. The combined THF layers were concentrated on a
rotovap and dried in vacuo to give N-cocoylglycine in 73%
yield.
Comparative Example
[0094] To show that correct solvent is required, applicants
conducted an experiment comparing the reaction for production of
N-lauroylmonoethanolamine as set forth in Example 5 in Japanese
patent application Ser. No. 10/087,554 (Assigned to Lion Corp.) to
the reaction of our invention. Results are set forth below.
TABLE-US-00002 Process Parameter JP 10/087,554 Our Invention Conc.
of Oxidant 5% (0.8 M) NaOCl 11.5% (1.85 M) NaOCl Amount of Oxidant
2.8 eq. NaOCl 3.25 eq. NaOCl Solvent Acetonitrile THF Phases
Acetonitrile was dissolved in 2-Phase System: Separate water and
only one liquid THF and aqueous layers. phase formed Two liquid
phases were present Location of LMEA LMEA undissolved in LMEA
dissolved in THF CH.sub.3CN/water --thick slurry layer. was
obtained. Added base No NaOH added to NaOCl 2 N NaOH added to NaOCl
pH Range pH 5.5 6.6 during reaction pH 13.2 7.4 during reaction
Reaction Temperature 33 35.degree. C. 24 26.degree. C. Reaction
Time 6 hr. including NaOCl addition 2 hr. including NaOCl time
addition time. Isolated Yield 81% >100% (water present) Purity
(HPLC Area %) 30.6% 68.5%
Summary of Oxidation Examples
[0095] A summary of the Examples for oxidation of LMEA to LG is set
forth in the Table below.
TABLE-US-00003 Reac Initial Peak Work- Yield Ex. NaOCl Time Temp
Temp Initial Final Isolation up as Yield No NaOCl:Substrate Conc.
Solvent (hr.) (.degree. C.) (.degree. C.) pH pH Method pH Acid as
Salt 1 6.5:1 11.5% THF 2 24 32 12.71 7.57 THF 3.0 116% 107%
Extraction 2 3.25:1 11.5% THF 2 24 26 9.89 7.61 THF 2.1 103% 95%
Extraction 3 3.25:1 11.5% THF 2 25.4 26.9 10.3 7.8 THF 8.3 108% 99%
Extraction 4 6.5:1 11.5% THF 2 24.8 30.2 11.56 7.24 Water 2.6 77%
71% Drowning 5 3.25:1 11.5% THF 3 23 25.2 10.35 -- Water 5.2 59%
55% Drowning 6 3.25 5% Water 21.sup.a 19.5 19.5 8.56 7.81 THF 2.5
114% 105% Extraction .sup.aActual reaction time may be less.
[0096] A summary of the Examples of the oxidation of
N-cocoylmethanolamide to N-cocoylglycine is set forth in the Table
below.
TABLE-US-00004 Reac Initial Peak Yield Yield Ex. NaOCl Time Temp
Temp Initial Final Isolation Work- as as No NaOCl:Substrate Conc.
Solvent (hr.) (.degree. C.) (.degree. C.) pH pH Method up pH
Acid.sup.b Salt.sup.b 7 3.25:1 11.5% Toluene 6.sup.a 31 38 -- 8.9
THF 2.2 84% 78% Extraction 8 3.25:1 11.5% Cyclohexane 16.sup.a 38.5
41 -- 6.2 THF 3.1 73% 67% Extraction .sup.aActual reaction time may
be less. .sup.bAssume CMEA and CG are each the corresponding 100%
C-12 compounds.
* * * * *