PROCESS FOR THE SYNTHESIS OF OMEGA-FUNCTIONALIZED ACIDS
FROM FATTY ACIDS OR ESTERS
The work which led to this invention received financial support from the European
Union in the context of Framework Program 7 (FP712007-2013) under the project number
No. 241718 EUROBIOREF.
A subject matter of the present invention is a process for the synthesis of
w-functionalized acids of formula R-(CH2),-COOH in which R represents COOH or
NH2CH2 from a feedstock of natural origin comprising hydroxylated fatty acids.
The polyamides industry uses a whole range of monomers, such as long-chain
diacids, diamines and w-amino acids. These polyamides, normally known as Nylon, are
characterized by the length of methylene chain (-CH2),- separating two amide functional
groups -CO-NH-. Thus it is that Nylon 6, Nylon 6,6, Nylon 6,10, Nylon 7, Nylon 8, Nylon 9,
Nylon 1 1, Nylon 13, and the like, are known.
These monomers are, for example, manufactured by a chemical synthesis route
using in particular, as starting material, C2 to C4 olefins, cycloalkanes or benzene, but also
fatty acids generally comprising 18 carbon atoms, resulting from unsaturated natural oils,
such as, in particular, soybean oil, corn oil, linseed oil, palm oil, and the like.
Current developments with regard to the environment are resulting in the use of
natural starting materials originating from a renewable source being favored in the fields of
energy and chemistry. This is the reason why some studies have been taken up to
develop, industrially, processes using fatty acidslesters as starting materials for the
manufacture of these monomers.
The main studies have related to the synthesis of 9-aminononanoic acid, which is
the precursor of Nylon 9, for oleic acid of natural origin. As regards this specific monomer,
mention may be made of the work "n-Nylons, Their Synthesis, Structure and Properties",
1997, published by J. Wiley and Sons, Chapter 2.9 of which (pages 381 to 389) is devoted
to Nylon 9.
As regards the synthesis of higher monomers, such as, for example, those
resulting, on the one hand, in Nylon 11 or in Nylon 13 and, on the other hand, in higher
diacids, only a little literature and a fortiori few industrial preparations are found.
They are directed virtually exclusively at the conversion of natural oils (castor oil,
olive oil, soybean oil, sunflower oil, palm oil, and the like) comprising unsaturated CIS fatty
acids, such as oleic acid and ricinoleic acid, lesquerella oil comprising CZ0 lesquerolic acid,
erucic rapeseed oil, lunaria oil or sea kale oil comprising C22 erucic acid.
One of the rare examples of an industrial process using a fatty acid as starting
material is that of the manufacture, from the ricinoleic acid extracted from castor oil, of
I I-aminoundecanoic acid, which forms the basis of the synthesis of Rilsan 11@. This
process is described in the work "Les Procedes de Petrochimie" [Petrochemical
Processes] by A. Chauvel et al., which appeared in Editions Technip (1986). 11-
Aminoundecanoic acid is obtained in several stages. The first consists of a methanolysis
of castor oil in a basic medium, producing methyl ricinoleate, which is subsequently
subjected to a pyrolysis in order to obtain, on the one hand, heptanaldehyde and, on the
other hand, methyl undecylenate. The latter is converted to the acid form by hydrolysis.
Subsequently, the acid formed is subjected to a hydrobromination to give the wbrominated
acid, which is converted by amination to I I -aminoundecanoic acid.
The use of hydroxylated fatty acids as starting material for the synthesis of amino
acids is not very common outside the industrial example mentioned above. However,
mention may be made of the patent application FR 2912741 on behalf of the applicant
company, which describes the synthesis of 11-aminoundecanoic acid and 12-aminododecanoic
acid by a process using in particular metathesis.
The most well known saturated diacids (or diesters) are those comprising chains
comprising from 4 to 6 carbon atoms, such as succinic acid (C4), glutaric acid (Cs), or
adipic acid (C6). They are generally synthesized by the chemical route or, more recently,
for succinic acid, by the fermentation route.
On the other hand, long-chain diacids are obtained either by fermentation of
paraffins or of fatty acids or also by oxidation of cycloalkane, as in the case of the
oxidation of cyclododecane to give dodecanedioic acid, or by cracking, in a basic medium,
ricinoleic acid to give sebacic acid (Clo diacid) or lesquerolic acid to give the CIP diacid
dodecanedioic acid.
The properties, syntheses and uses of these diacids are described in Ullmann's
Encyclopedia, Vol. A8, pages 526-536. The saturated or unsaturated diacids are generally
obtained industrially according to the various methods mentioned in this reference. Apart
from the syntheses by condensation or fermentation, methods by decomposition, such as,
in particular, the ozonolysis, the oxidation or the cracking of optionally hydroxylated
unsaturated fatty acids, are encountered (pages 526, 527 and 532 of this publication). In
the patent applications published under the numbers FR 2917406 and FR 2921363, the
applicant company describes this type of synthesis applied to unsaturated fatty acids.
The use of natural oils as source of unsaturated fatty acids presents a tricky
problem insofar as they consist of a mixture of various saturated and unsaturated acids,
optionally polyunsaturated acids, which results in the formation, during the treatment, in
particular when oxidative cleavage is employed, of multiple by-products due to the
presence of multiple unsaturations which require expensive separationlpurification
treatments. This is true both for the fatty acids and for the hydroxylated fatty acids.
The problem posed by the presence, within the oil, of various unsaturated fatty
acids exists with all the more acuteness as, in the future, in order to improve productive
outputs, there will be increasing prompting to use GMO plants.
In order to illustrate this phenomenon, mention may be made of the publication by
Linnaeus Plant Science (Jack Grushcow, "Optimising Oil Seed Potential for lndustrial
Application", Renewable Resources and Biorefineries Conference, 6-8 September 2006,
The University of York, York, UK, and Jack Grushcow, "lndustrial Oil Seed Opportunities",
Soy20-20, September 2004, Annual Meeting) which describes a mechanism of formation
of the various hydroxylated fatty acids synthesized in a process using Arabidopsis thaliana
as model plant. According to this process, oleic acid, the main acid produced, can be
converted by hydroxylation into ricinoleic acid, itself converted by dehydrogenation into
densipolic acid, the latter two being capable, by "elongation", of respectively forming
lesquerolic acid and auricolic acid.
The invention is targeted at overcoming these disadvantages by using, as starting
material, a natural oil rich in unsaturated hydroxylated fatty acids which are converted to
saturated hydroxylated fatty acids, the latter then being dehydrated to give
monounsaturated fatty acids which are optionally converted to nitriles and subsequently
subjected to oxidative cleavage, resulting in the w-functionalized acids, capable of being
converted into dinitriles.
In order to simplify the account, the expression "unsaturated hydroxylated fatty
acids" would denote the acids whether they are in the acid form, in the ester form or in the
polyol ester form, corresponding in practice, in the latter case, to the crude oil.
A subject matter of the present invention is a process for the synthesis of
w-functionalized acids of formula R-(CH2),-COOH, in which R represents COOH or
NH2CH2 and n represents an integer between 9 and 12, from a feedstock of natural origin
comprising unsaturated hydroxylated fatty acids in the acid, ester (such as methyl) or
polyol ester (such as glyceride oil; however, for reasons of ease of reading, reference will
be made subsequently to acid to denote equally well acids and esters of alcohols or of
polyols) form comprising at least 18 carbon atoms per molecule, comprising the following
stages:
a) hydrogenation of the unsaturated hydroxylated fatty acids, resulting in saturated
hydroxylated fatty acids,
b) dehydration of the saturated hydroxylated fatty acids, resulting in monounsaturated
fatty acids,
c) oxidative cleavage at the double bond of the monounsaturated fatty acids,
including unsaturated nitrile derivatives, resulting in an a,w-bifunctional compound
of diacid or nitrile-acid type (or from diacid or nitrile-acid).
The term "acid", in particular "unsaturated hydroxylated fatty acid", as starting
material for the process of the invention, for example as defined in the above
hydrogenation stage a) and for the continuation of the description, means and includes,
systematically, for the continuation (if reference is made to "acid" as starting material),
unless more specifically indicated (means and includes), equally well acids and esters of
alcohols (such as methyl esters) or esters of polyols (such as glycerol esters, which is the
oil) for these fatty acids.
Properly, according to a more specific form of the invention, the starting "acid"
material can be in the ester form of said fatty acid.
In the final case of a product which is an a,w-nitrile-acid compound, according to
the process of the present invention, use is made at the start, as starting material for the
oxidation reaction, of an unsaturated fatty nitrile prepared, according to a first option, after
stage b), by ammoniation (treatment of said fatty acid with ammonia).
According to a second option of the process, said a,w-nitrile-acid compound can
also be prepared from an unsaturated nitrile resulting from the nitrilation of the
hydrogenated acid resulting from stage a) carried out at the same time as the dehydration
stage b).
Thus, the nitrilation resulting in said unsaturated nitrile, the starting material for the
oxidative cleavage of stage c), can be prepared either during a separate stage after the
dehydration stage b) or at the same time as the dehydration stage b). Preferably,
dehydration and ammoniation are carried out simultaneously.
Generally, for the invention, the term "... is between a and b means, unless
otherwise specified, "...is between a and b with a and b included" or means the same
thing as "...varies from a to b").
According to one option of this process, the hydrogenation stage a) is carried out
at a temperature of between 70 and 180°C, preferably between 70 and 150°C, more
preferably between 90 and 130°C, under an Hq pressure of between 1 and 300 bar,
preferably between 5 and 50 bar, in the presence of either homogeneous or
heterogeneous hydrogenation catalysts. Said catalysts can be noble metals, such as Pt,
Pd or Rh, or transition metals, such as Mo, W, Cr, Fe, Co or Ni, used alone or as a
mixture, optionally in the form supported on active charcoal, on alumina and on silica.
Mention may be made, among said catalysts, of Raney nickel and/or palladium-on-active
charcoal.
The process of the invention can use, as feedstock, either the fatty acid or the fatty
ester resulting from the prior hydrolysis or prior alcoholysis of the natural oil, or the crude
oil itself. In the latter case, it will be necessary to provide an additional stage of hydrolysis
or alcoholysis prior to the oxidative cleavage, in order to separate the glycerol from the
reaction medium.
The hydrogenation stage is carried out under operational conditions such that the
double bonds present in the feedstock, which simultaneously comprises unsaturated
hydroxylated fatty acids and saturated, monounsaturated or polyunsaturated fatty acids,
are saturated, while retaining the hydroxyl functional groups present.
According to a specific case, the hydrogenation stage a) is carried out under
operational conditions such that the effluent resulting from this hydrogenation stage
exhibits an iodine number < 5, preferably < 3 and more preferably < 1 and a hydroxyl
number > 100 mg KOHIg.
The effluent resulting from this hydrogenation stage will thus exhibit an iodine
number (as defined in Vol. A 10, page 214, of Ullmann's Encyclopedia) of less than 5,
preferably of less than 3 and more preferably of less than 1 and a hydroxyl number (as
defined in Vol. A 10, page 214, of Ullmann's Encyclopedia) of greater than 100 mg KOHIg.
The operating conditions will be such that the reduction in the hydroxyl number of the
reaction medium at the end of this hydrogenation stage will be 5 10 mg KOHIg.
As regards the stage b) of dehydration of the saturated hydroxylated fatty acids, it
is carried out at a temperature of between 100 and 300°C and in the presence of an acid
catalyst, preferably chosen from: sulfuric acid, phosphoric acid, sulfonic acids, alkyl
sulfonates or ion-exchange acid resins, such as resins of ~mberlystyt~pe .
As regards the oxidative cleavage stage c), it is carried out using an oxidizing
agent chosen from KMn04, hydrogen peroxide or oxidizing ozone, optionally in
combination with a catalyst (for example tungstic acid), in particular ozone in combination
with oxygen.
The invention relates both to the diacids and the a,w-amino acids obtained
according to the process of the invention.
According to one option, the process of the invention comprises an additional
intermediate stage, between stage b) as defined above and stage c) as defined above, of
nitrilation of the acid functional group of the monounsaturated fatty acid, resulting in an
unsaturated nitrile.
According to yet another specific option, the process of the invention comprises a
stage of nitrilation of the acid functional group of the saturated hydroxylated fatty acid
resulting from stage a) with concomitant (or simultaneous) dehydration, resulting in an
unsaturated nitrile.
Said nitrilation stage can be carried out in the liquid phase or in the gas phase
using ammonia at a temperature generally of between 150°C and 350°C and with a
catalyst.
More particularly, said nitrilation is carried out in the liquid phase with, as catalyst,
a metal oxide which is zinc oxide. More particularly still, said nitrilation is carried out in the
gas phase with said catalyst being, for example, supported on a fixed bed of doped or
non-doped alumina.
According to the process of the invention, the effluent from the nitrilation stage can
be subjected to the oxidative cleavage stage c) defined above, the effluent (comprising the
nitrile-acid compound) of which is subjected to a hydrogenation d), as described below.
In particular, the hydrogenation stage is carried out at a temperature of between 70
and 200°C, preferably between 70 and 150°C and more preferably between 90 and
1 30°C, under an Ha pressure of between 1 and 300 bar, preferably between 5 and 50 bar,
in the presence of either homogeneous or heterogeneous hydrogenation catalysts.
The hydrogenation of the unsaturated fatty acids is a well known reaction.
Reference may be made, on this subject, to Vol. A 10 of Ullmann's Encyclopedia,
pages 189, 207 to 209 and 267 to 269. This hydrogenation stage can be carried out at a
temperature of between 70 and 150°C, preferably between 90 and 130°C and more
preferably at approximately 120°C, under an H, pressure of between 1 and 300 bar,
preferably between 5 and 50 bar and more preferably at approximately 20 bar. The
process is carried out in the presence of either homogeneous or heterogeneous
hydrogenation catalysts and preferably heterogeneous hydrogenation catalysts. These
catalysts will, for example, be noble metals, such as Pt, Pd or Rh, or transition metals,
such as Mo, W, Cr, Fe, Co or Nil used alone or as a mixture. They can be deposited on
supports, such as active charcoal, alumina and silica. The preferred catalysts are Raney
nickel or palladium-on-active charcoal. The amount of catalyst used represents from 0.2%
to 5% by weight and preferably from 0.4% to 2% by weight of the treated feedstock.
The hydrogenation stage a) is preferably carried out under operational conditions
such that the effluent resulting from this hydrogenation stage exhibits an iodine number
< 5, preferably < 3 and more preferably < 1 and a hydroxyl number > 100 mg KOHIg.
The stage b) of dehydration of the saturated hydroxylated fatty acids is
conventionally carried out at a temperature of between 200 and 300°C in the presence of
an acid catalyst. This catalyst can be sulfuric acid, phosphoric acid, sulfonic acids, alkyl
sulfonates or ion-exchange acid resins, such as resins of ~mberlystty~pe or of other type.
A copious and long-standing literature exists on the dehydration of castor oil.
Mention may in particular be made of the patents GB 671368, 687986, 691484, 703363
and US 2 567 925, and also in the Kirk-Othmer Encyclopedia, Vol. 8, page 526. It should
be noted that the dehydration results in a mixture of two monounsaturated fatty acids, the
double bond which is located either in the "6-n" position or in the "6-n+l" position with
respect to the acid functional group. On considering, for example, ricinoleic acid, the
mixture will be 61 1 plus 612 and on considering, for example, lesquerolic acid, the mixture
will be 613 plus 614.
The stage c) of oxidative cleavage of the double bond of the monounsaturated fatty
acids or nitriles, which results in the formation of the acid functional group on, the two
carbons of the double bond, is also known per se. It can be carried out using a wide range
of strong oxidizing agents.
The oxidative cleavage stage c) can be carried out by using, for example, a strong
oxidizing agent, such as KMn04 in the concentrated form, and with heat, as is described
in "Organic Chemistry" by L.G. Wade Jr., 5th Edition, Chapter 8: Reactions of Alkenes.
The oxidative cleavage can be obtained via a sulfuric acidlchromic acid derivative,
such as described in the patent USP 2 871 247, in columns 2 and 3.
The oxidative cleavage stage c) can be carried out by using hydrogen peroxide, as
described in the patent GB 743 491, optionally in combination with a catalyst. The use of
H202 is also described in the patent WO 20071039481 (Novamont).
Mention may also be made of the work "Angew. Chem. Int. Ed.", 2000, 39,
pp. 2206-2224, which describes the oxidative cleavage of the double bond either with a
peracid, in combination with a ruthenium-based catalyst, or with H202w, ith catalysts based
on Mo, W or Re.
Numerous studies have been carried out on the use of ozone as oxidizing agent.
Moreover, it is mentioned, in the "Angew. Chem." work cited above, that the oxidative
cleavage of oleic acid to give pelargonic acid and azelaic acid is the most important
industrial application of ozonolysis.
Oxidative ozonolysis is very widely used to carry out cleavage. The patent
US 2 81 3 11 3 describes in particular a process for the oxidative ozonolysis of a fatty acid,
such as oleic acid, which consists, in a first stage, in treating the acid with oxygen in
combination with ozone, in order to form ozonides, and then, in a second stage, in
oxidizing the latter by the oxygen.
In this type of reaction, compounds which block the oxidation process at the stage
of the ketones or aldehydes, in what is referred to as reductive ozonolysis, are not used.
Thus, the oxidative cleavage stage c) can be carried out by using ozone in
combination with oxygen.
Another subject matter of the invention is diacids prepared according to the above
process.
When the process of the invention is intended for the synthesis of w-amino acid, it
will comprise, on the one hand, an additional intermediate stage of nitrilation
(ammoniation) of the acid functional group according to the reaction R-COOH + NH3 3
R-CN + 2 H20 and, on the other hand, a final stage of reduction of the nitrile functional
group to give a primary amine functional group. The overall reaction scheme is described
later.
Thus, in a specific embodiment of the invention, the process comprises an
additional intermediate stage b'), between stage b) and stage c), of nitrilation of the acid
functional group of the monounsaturated fatty acid resulting in an unsaturated nitrile.
Alternatively, the process can comprise a stage a'), between stage a) and stage b),
of nitrilation of the acid functional group of the saturated hydroxylated fatty acid resulting
from stage a), with concomitant dehydration, resulting (subsequent to dehydration) in an
unsaturated nitrile.
The reaction for nitrilation (or ammoniation, the two terms being used without
distinction) of the fatty acids is well known and follows the following simplified reaction
scheme:
NH3
R-COOH ----, [R-COO@ NH?] - [R-CONH~] - R-CN + H20
+
H20
The nitrilation stage can be carried out in the liquid phase (batch process) or in the
gas phase (continuous process) by means of ammonia, at a temperature generally of
between 150°C and 350°C, with a catalyst.
The liquid-phase process is carried out at a temperature of between 150°C
approximately (first phase) and 250"-300°C (second phase) with a catalyst which is
generally a metal oxide and most frequently zinc oxide.
In the continuous process, the reaction takes place in the gas phase at high
temperature levels and generally over a catalyst consisting of a fixed bed of alumina,
which is or is not doped. The fatty acid is vaporized in the presence of a large amount of
ammonia, the excess of which is recycled. The process can thus be carried out in the gas
phase with, as catalyst, a fixed bed of alumina, which is or is not doped.
In the gas-phase version, many other catalysts can be used and there exists
copious literature on this subject. Mention may be made, for example, of the document
JP 2000-16977, which describes catalysis with niobium oxide at a temperature of 260°C
(stearic acid), or the document JP 2000-7637, which describes a process carried out at a
temperature ranging from 180" to 350°C, also with a catalyst of niobium oxide type.
US 6 005 134 describes catalysis with titanium and, finally, JP 10-1 95035 describes
catalysis with iron-doped zirconium oxide.
In a specific embodiment of the invention, the effluent from the nitrilation stage is
subjected to the oxidative cleavage stage c), the nitrile-acid effluent from which is
subjected to a hydrogenation.
The final hydrogenation reaction of the nitrile-acid compound is carried out under
conditions analogous to those described above for the initial hydrogenation reaction.
Raney nickel, deposited or not deposited on a support, such as silica, is the catalyst most
generally adopted. The use of other metals known for their catalytic activity in
hydrogenation has also been envisaged under heterogeneous conditions. Mention may be
made, for example, of platinum, palladium, ruthenium or iridium, alone or in combination.
Mention may be made, on this subject, of GB'I 273 874, which describes the use of a
ruthenium catalyst deposited on silica.
In one embodiment of the alternative form targeted at the synthesis of amino acids,
it will be possible, in some cases, to carry out the ammoniation stage directly after the
initial hydrogenation stage. This is because, under the conditions of the ammoniation, the
dehydration of the hydroxylated fatty acid can occur spontaneously, which makes it
possible to eliminate an intermediate stage.
In the case where the feedstock is composed of the crude oil, an additional
hydrolysis stage is necessary and can occur either after the initial hydrogenation stage or
after the hydrogenation and dehydration stages.
The operating conditions for the hydrolysis stage are well known to a person skilled
in the art. They are described in particular in Ullmann's Encyclopedia, Vol. A 10, pages
188 and 254 to 260.
Naturally, it is perfectly possible to carry out, between each stage, the separation
of the compounds reacting in the following stage from the "useless" compounds.
Likewise, at the end of the process, it is necessary to separate the two forms of
amino acids or of diacids, for example the Cll and C12 forms or the Cl3 and C14 forms
originating from the dehydration stage.
The techniques of the separation of fatty acids in a mixture are well known and are
extensively described in Ullmann's Encyclopedia, Vol. A 10, pages 260 to 267. They are
essentially based on distillation and crystallization and their various alternative forms. The
choice of the technique will depend on the difference in the temperatures of change of
state of the constituents of the mixture, liquidlgas (distillation) or liquid-solid
(crystallization). It is also possible to envisage liquid-liquid extractions using suitable
solvents or chromatographic separations.
In an alternative embodiment of the process of the invention, it is possible to
envisage enriching the reaction medium in one of the targeted amino acids or diacids by
adding thereto, during processing, either after the initial dehydrogenation stage or after the
dehydration stage, a fatty acid comprising just one olefinic unsaturation in a suitable
position 611, 612, 613 or 614. By way of examples, it will be possible to add, to the
medium, if the main target is the Cll amino acid, vaccenic acid andlor gondoic acid.
Likewise, it will be possible to add, to the medium, erucic acid in order to increase the
proportion of CI3 diacid or CI3 nitrile-acid.
The process is particularly advantageous for feedstocks comprising densipolic acid
and auricolic acid, as or not as a mixture with ricinoleic acid and lesquerolic acid, as, after
hydrogenation, saturated acids having the same Cis or C 2c~ha in length are obtained.
In the implementation of the process of the invention, the choice will preferably be
made of feedstocks rich in ricinoleic acid or densipolic acid, resulting in CI1 or CI2 nitrileacids
resulting in the corresponding w-amino acids, and feedstocks rich in lesquerolic acid
or auricolic acid, resulting in the C13 or CI4 diacids.
The process of the invention makes it possible to synthesize, depending on the
alternative form employed, either a fatty diacid or a fatty amino acid comprising from 11 to
14 carbon atoms per molecule, this depending on the composition of the feedstock
treated.
The reaction schemes of the process are illustrated below taking as example
ricinoleic acid, which is the commonest of the unsaturated hydroxylated fatty acids. If the
feedstock treated is in the ester form, the reaction schemes below will be identical except
that the H of the acid functional group is replaced by an alkyl radical (simple alcohol ester,
such as methyl ester, for example) or by a radical comprising 2 or 3 carbon atoms
respectively carrying 1 or 2 alcohol or ester functional groups (polyol esters, such as
glycerol esters, for example).
Diacid alternative form
CH3-(CH2)5-CHOH-CH2-CH=CH-(CH2)7-COO+H H 2 3 CH3-(CH2)5-CHOH-(CH2)10-COOH
The dehydration results in a mixture of unsaturated fatty acids according to
CH3-(CH2)5-CHOH-(CH2)lo-COO3H CH3-(CH2)4-CH=CH-(CH2)lo-COO+H H 20o r
CH3-(CH2)5-CHOH-(CH2)lo-COOH3 CH3-(CH2)5-CH=CH-(CH2)9-COO+H H 20
Oxidative cleavage thus results in a mixture of diacids
CH3-(CH2)4-CH=CH-(CH2)lo-COOH(+ OXY.)+ HOOC-(CH2)10-COOH+ CH3-(CH2)4-COOH
and CH3-(CH2)5-CH=CH-(CH2)9-COO(H+ Oxy.) 3 HOOC-(CH2)9-COOH+ CH3-(CH2)5-COOH
Amino acid alternative form
CH3-(CH2)5-CHOH-CH2-CH=CH-(CH2)7-COOH + H2 3 CH3-(CH2)5-CHOH-(CH2)10-COOH
The dehydration results in a mixture of unsaturated fatty acids according to
CH3-(CH2)5-CHOH-(CH2)lo-COOH. ) CH3-(CH2)4-CH=CH-(CH2)lo-COO+H H 20o r
CH3-(CH2)5-CHOH-(CH2)lo-COOH. ) CH3-(CH2)5-CH=CH-(CH2)9-COO+H H 20
The nitrilation results in the fatty nitriles according to
CH3-(CH2)4-CH=CH-(CH2)~~-CO+O NHH 3 3 CH3-(CH2)4-CH=CH-(CH2)10-C+N 2 H20o r
CH3-(CH2)s-CH=CH-(CH2)g-COOH+ NH3 4 CH3-(CH2)5-CH=CH-(CH2)9-C+N 2 H20
Oxidative cleavage thus results in a mixture of nitrile-acids
CH3-(CH2)4-CH=CH-(CH2)lo-CN (+ Oxy.) 3 HOOC -(CHS)~~-C+ NC H3-(CH2)4-COOHa nd
CH3-(CH2)5-CH=CH-(CH2)g-CN (+ OXY.) 4 HOOC -(CH2)g-CN + CH3-(CH2)5-COOH
Finally, the hydrogenation of the nitrile-acids results in the amino acids according
t 0
HOOC -(CH2)10-CN+ 2 H2 3 HOOC -(CH2)10-CH2NHa2n d
HOOC -(CH2)g-CN + 2 H2 3 HOOC -(CH2)g-CH2NH2
The stage of nitrilation of the fatty acids occurs after the hydrogenation stage. It
can follow the dehydration stage but, in some cases, the nitrilation conditions will make
possible the concomitant dehydration of the saturated hydroxylated fatty acid, which will
be particularly advantageous.
Another subject matter of the invention is w-amino acids prepared according to the
above process.
At a practical level, the process will preferably be able to comprise the sequence of
following stages, starting from a feedstock of natural origin comprising unsaturated
hydroxylated fatty acids in the ester form (alcohol or polyol ester, such as glycerol ester)
and in particular in the form of hydroxylated oil of corresponding fatty acid (the oil being a
glycerol ester), with said stages being:
i) hydrogenation of the hydroxylated ester, in particular the corresponding oil
ii) dehydration of the hydrogenated hydroxylated ester, in particular of the
corresponding oil
iii) hydrolysis of the hydrogenated (and dehydrated) ester, in particular of the
corresponding oil, in order to obtain the corresponding unsaturated fatty acid and
alcohol or polyol, in particular glycerol
iv) separation of the alcohol or polyol, in particular glycerol, and optionally separation
of the unsaturated fatty acid isomers (for example, separation of the
I 1 -0ctadecanoic from the 12-octadecanoic)
v) optionally (only in the case of nitrile), ammoniation of the unsaturated (fatty) acid in
order to obtain the corresponding unsaturated nitrile
vi) oxidative cleavage of the unsaturated nitrile or fatty acid (as the case may be)
vii) optionally, separation of the cleavage products and light acids formed (for
example, of the I I -nitrile-acid from the 12-nitrile-acid, in the case of the nitrile)
viii) optionally (case of nitrile), hydrogenation of the nitrile-acid in order to form the
corresponding amino acid
ix) separation and purification of the diacid formed or of the amino acid formed, as the
case may be.
According to another more specific option of said process where the objective is
first a nitrile-acid and then a corresponding amino acid, said a-functionalized acid is thus
an amino acid and said feedstock of natural origin comprises unsaturated hydroxylated
fatty acids in the ester (alcohol or polyol ester, such as glycerol ester) form, in particular in
the form of a hydroxylated oil (glycerol ester), and said process comprises the sequence
of the following stages:
i) hydrogenation of the hydroxylated ester, in particular of the corresponding oil
ii) hydrolysis of the hydrogenated ester, in particular of the corresponding oil, in order
to obtain the corresponding saturated fatty acid (for example 12-hydroxystearic
acid)'and alcohol or polyol, in particular glycerol
iii) separation of the alcohol or polyol, in particular glycerol, with optional separation of
the saturated fatty acids from the hydroxylated fatty acids
iv) ammoniation of the saturated hydroxylated acid, with simultaneous dehydration, in
order to obtain the corresponding unsaturated nitrile
v) optionally, separation of the unsaturated nitrile isomers
vi) oxidative cleavage of the unsaturated nitrile
vii) optionally, separation of the nitrile-acid cleavage products and of the light acids
formed
viii) hydrogenation of the nitrile-acid, in order to obtain the corresponding amino acid
ix) separation and purification of the amino acid obtained.
In the case where the objective is a nitrile-acid and then an amino acid, starting
from a vegetable oil source which has a low concentration of hydroxylated acid, it is
possible to provide a slightly different sequence:
i) alcoholysis (for example or in particular methanolysis) of the vegetable oil,
optionally concomitant with its extraction from the seed
ii) extraction of a fraction rich in hydroxylated acid ester
iii) hydrogenation of the hydroxylated ester
iv) optionally, hydrolysis of the hydrogenated ester in order to obtain the
corresponding fatty acid (for example, production of 12-hydroxystearic acid or
14-hydroxyeicosanoic acid)
v) ammoniation of the saturated hydroxylated acid with simultaneous dehydration
(including on ester of stage iii) or on acid of stage iv)), in order to obtain the
unsaturated nitrile
vi) optionally, separation of the unsaturated nitrile isomers
vii) oxidative cleavage of the unsaturated nitrile
viii) optionally, separation of the nitrile-acid cleavage products (comprising 11 and 12
carbons, for example) and of the light acids formed
ix) hydrogenation of the nitrile-acid
x) separation and purification of the amino acid.
The examples which follow illustrate in an even more detailed manner the present
invention, without any limitation, by these examples, of its coverage.
Experimental part
Example 1 : Production of lesquerella oil
The procedure with regard to 25 kg of seeds is as follows:
1. Flaking of the fresh lesquerella seed on a smooth roll crusher.
2. The flakes are subsequently dried at 100°C for 16 h.
3. The flakes are introduced into a percolation column.
4. The methanollhexane (50150 by weight) mixture is then circulated over the bed at
40°C for 30 minutes.
5. The miscella is subsequently withdrawn and the bed of flakes is subsequently
washed by 5 successive washing operations with the methanollhexane mixture at
40°C (5 minutes per washing operation).
6. The miscella is then evaporated under vacuum at 90°C under 20 mbar for 5 min.
7. The oil and the gums are separated by centrifuging. The oil yield is calculated on
the basis of the weight of oil obtained versus the theoretical weight of oil expected.
8. The oil is subsequently washed to neutrality by addition of hot water and
centrifuging and then it is dried under vacuum at 90°C and 20 mbar for 5 min. The
acid number and the composition of this oil are then measured.
Table A: Mass balance of the process of nonreactive trituration of the lesquerella seed in
the presence of a methanollhexane mixture
Solids yield (Yd), % (1) 1 107.8 1
Conditions
Close-spaced smooth roll crusher
Drying 100°C, 16 h
Flake thickness, mm
SolventslSeed ratio by weight
I
Phase separation I No
Test 10-E47
Yes
Yes
0.16 to 0.18
2
Test Balance
I (Oil cake MG content, %)
Oil Yd, %
Oil potential in the oil cake, %
Yd of insoluble materials in the oil extracted by centrifuging, % I 0.0
107.8
2.4
the sum of the theoretical amounts of theoretical oil
(2) Oil loss = 100 - Oil Yd - Oil cake oil pot.
Comments:
- In the presence of a methanollhexane mixture, the extraction yield is of the same
I
order as with methanol alone (a 108%), whereas the extraction temperature was
Oil loss (calculated value), % (2)
reduced to 40°C in order to prevent the hexane from boiling;
-1 0.2
the content of insoluble material is zero, appearing to indicate that, if there had
been extraction of gums, the latter are partially liposoluble (< 10% in the oil);
(1) The solids yield is the ratio, times 100, of the solids obtained after evaporation of the miscella to
the oil cake remains relatively well extracted (0.9%);
the phospholipids content of the oil is 1.3%;
qualitatively, the extracted oil is highly acidic (AN > 11). It is highly probable that
the dissolved gums exhibit a significant acidity. Furthermore, the expected content
of lesquerolic acid (52%) is found.
Table 1: Analysis of the oil extracted with a methanollhexane mixture
Criteria
I I
Fatty acids profile
I I
I Palmitic (C16:O) I 1 1.6 I
Method
Acid number (mg KOHIg)
I Palmitoleic (C16: I ) I 1 0.9 I
Test 10-E47 oil
EN 14104 1 11.2
I Stearic (C18:O) I 1 I Oleic (C18:l) I 1 21.83. 8 II
Ricinoleic (C18: 1 -OH)
Linoleic (C18:2) I Densipolic (I 8:2-OH) I 1 I Linolenic and arachidic I 1 01.12. 6 (1) II 1 Eicosenoic (C20: I ) I 1 0.9 I
I Auricolic (20:2-OH) I 1 2.6 I
(2) Calculated value; % phospholipids = % phosphorus x 26
(3) Corrected Yd = Extraction Oil Yd (Table 1) - % phospholipids
Phospholipids (%)
Corrected yield of oil (3), %
The oil thus obtained is subsequently refined by neutralization with sodium
hydroxide and degumming with diluted phosphoric acid, so as to remove the
(1) The two peaks are coeluted. Linolenic acid is predominant
Internal
-
phospholipids. Finally, the oil is dried under vacuum. The oil obtained has the following
1.3 (2)
106.5
characteristics:
Acid number: 0.5 mg KOHlg
Saponification number: 175 mg KOHIg
Hydroxyl number: 100 mg KOHIg
Iodine number: 95 g 1,1100 g
Lesquerolic acid content: 52%
Phosphorus content: 10 ppm
Water and volatiles content: 0.1 % by weight
Ash content: 0.1 % by weight.
Example 2: Preparation of hvdroaenated lessuerella fatty acids
In a first step, the lesquerella oil is transesterified, then hydrogenated and, finally,
hydrolyzed. An extraction stage after the transesterification makes it possible to enrich the
product in lesquerolic acid ester.
The methanolysis of the lesquerella oil is carried out with a methanolloil molar ratio
of 6 (i.e., twice the stoichiometric amount). The catalyst used is sodium methoxide at a
content of 0.5% by weight and the reaction temperature is 60°C. The constituents are
mixed with vigorous stirring for 30 minutes. After methanolysis (transesterification) and
removal of the glycerol by separation by settling, the esters are purified by washing with
water and drying under vacuum. The specifications of the methyl esters are as follows:
Acid number: 0.5 mg KOHIg
Saponification number: 175 mg KOHIg
Iodine number: 95 g 12/1 00 g
Content of residual glycerides (analysis by GPC): 1.9% by weight
Lesquerolic acid content: 52%
The mixed methyl esters obtained in the preceding stage are hydrogenated in an
autoclave (in several goes, as a result of the size of the autoclave). Use is made of a
catalyst of Raney nickel type supplied by Johnson Matthey, at a content of 0.5% by
weight. The hydrogenation temperature is 150°C, under a hydrogen pressure of 8 bar.
This stage results in a product having an iodine number of 3 g 121100 g and a hydroxyl
number of 93 mg KOHIg.
Finally, a saponification stage is carried out by addition of sodium hydroxide to the
mixture of esters and then an acidification stage is carried out with sulfuric acid. The
resulting mixture is washed with water, separated by settling and dried under vacuum. The
fatty acid mixture obtained has the following characteristics:
Acid number of 180 mg KOHIg
Hydroxyl number of 90 mg KOHIg
Iodine number of 3 g 12/100 g
The 14-hydroxyeicosanoic acid content is 50%.
Example 3: Preparation of a mixture enriched in 14-hvdroxveicosanoic acid
The mixture of esters resulting from the transesterification stage as in example 2,
but starting from a commercial lesquerella oil, is subjected to a stage of liquid-liquid
extraction with a methanollhexane mixture. In a practical implementation of the example,
the methanol comprises 5% by weight of water. The nonhydroxylated fatty acids are more
compatible with the hexane phase, whereas the hydroxylated fatty acids, such as
lesquerolic acid, are more compatible with the methanolic phase.
In this example, the hexane was used as nonpolar solvent. As a reminder, the
polar solvent consists of hydrated methanol. A succession of depleting and enriching
stages is carried out.
1. 5 g (methyl ester of lesquerella oil) + 30 ml of nonpolar solvent + 15 ml of polar
solvent are stirred for 5 minutes in a separating funnel and give a heavy phase
HPI + light phase LPI.
The light phase LP1 is taken up with 15 ml of polar solvent and again gives a
heavy phase HP2 and a light phase LP2.
The heavy phase HPI and the heavy phase HP2 are taken up with 30 ml of
nonpolar solvent and again give a heavy phase HP3 and a light phase LP3.
The heavy phase HP3 is taken up with 30 ml of nonpolar solvent to give a heavy
phase HP4 and a light phase LP4.
The fractions recovered are subsequently concentrated by evaporation of the
solvents.
1. The heavy phase HP4 gives the polar fraction.
2. The light phases LP2 + LP3 + LP4 are combined to give the nonpolar fraction.
Table 2: Analytical balance of the esters resulting from the extraction
Polar solvent
Nonpolar solvent
Yd by weight, %
Methyl lesquerolate extraction, Yd, %
Acid number
Me C16:l (%)
Me C16 (%)
Me C18:2 (%)
Me C18:l (%)
Me C18:O (%)
Me C20:O (%)
Me C20: 1 (%)
Me C18: 1 -OH (%)
Starting
material
0.72
0.5
1.3
9.1
23.5
1.8
0.9
1 .O
0.3
Heavy phase
95% Methanol
Hexane
16.5
25.4
nd
0.1
0.1
0.6
0.3
0.1
0.0
0.0
0.2
Light phase
95% Methanol
Hexane
83.5
74.8
1.12
0.6
1.6
11.7
27.5
2.2
1.1
0.7
0.3
With regard to the fraction enriched in lesquerolic acid, a hydrogenation and a
hydrolysis are carried out, as in the preceding example, in order to obtain a mixture rich in
14-hydroxyeicosanoic acid.
The characteristics of the mixture obtained are:
Acid number of 1 mg KOHIg
Hydroxyl number of 145 mg KOHIg
Iodine number of 3 g 12/100 g
14-Hydroxyeicosanoic acid content of 89%.
Example 4: Preparation of 12-hydroxystearic acid
In this example, the procedure is carried out as in example 6.1, test 09-E08, of the
patent application WO 20101076527, by reactive trituration of castor oil plant seeds. The
mixture of methyl esters is subsequently hydrogenated and hydrolyzed. As in example 2,
a mixture rich in 12-hydroxystearic acid is obtained.
After the reactive trituration stage, a mixture of methyl esters having an acid
number of 0.46 mg KOHIg is obtained, comprising 0.85% of palmitic acid ester, 2.9% of
linoleic acid ester, 3.46% of oleic acid ester, 0.96% of stearic acid ester and 90.65% of
ricinoleic acid ester. The mixture also comprises 1.19% of monoglycerides.
The mixture of esters is -then hydrogenated in the presence of a Raney nickel
catalyst (1% by weight), under a pressure of 20 bar of hydrogen and at a temperature of
130°C. The reaction is carried out in 2 hours. The final product is subsequently saponified
with sodium hydroxide and acidified with sulfuric acid. After washing, a mixture rich in
12-hydroxystearic acid is obtained, comprising 0.9% of palmitic acid, 0.3% of linoleic acid,
0.4% of oleic acid, 7.8% of stearic acid and 90% of 12-hydroxystearic acid.
Example 5: Preparation of isooleonitrile (this expression is used to indicate a mixture of
unsaturated isomers comprisinn 18 carbon atoms) from commercial 12-hvdroxvstearic
-acid
In this example, use is made of a commercial 12-hydroxystearic acid supplied by
Mosselman. This batch has the following specifications:
Acid number: 177 mg KOHIg
Saponification number: 182.5 mg KOHIg
Iodine number: 2.3 g 12/ 100 g
Hydroxyl number: 162.7 mg KOHIg.
This stage consists in reacting ammonia with the fatty acid at high temperature in
the presence of a catalyst (zinc oxide), in order to obtain the corresponding nitrile. The
reaction mechanism is probably a conversion of the acid to the ammonium salt, then to
the amide and finally to the nitrile. Due to the extreme conditions of this reaction, the
hydroxylated acid simultaneously dehydrates.
In order to carry out this reaction, use is made of an arrangement consisting of a
reactor heated by a heating mantle, surmounted by a condenser (dephlegmator) which
returns the heavy compounds to the reactor and allows the water resulting from the
reaction and also the excess ammonia to pass. The reactor is fed with gaseous ammonia.
The ammonia bottle is positioned on a balance in order to be able to monitor the amount
used.
250 g of 12-hydroxystearic acid are charged to the reactor. 0.16 g of zinc oxide
catalyst is added. The temperature of the mixture is brought up to the melting of the acid
(82°C) and then, with stirring to 205°C. At this temperature, the ammonia is added to the
reactor, the flow rate being gradually increased up to 0.417 liters1minute.kg. Subsequently,
the temperature of the reactor is increased up to 300°C. The temperature of the
dephlegmator is maintained at 130°C.
The temperature of the reactor is maintained at 300°C until an acid number of less
than 0.1 mg KOHIg is achieved. The progress of the reaction is followed by measuring the
acid number and the amount of water condensed at the reactor outlet. In the present case,
the excess ammonia is not recycled but it can be recycled industrially. After reacting for 10
hours and after the addition of 72 g of ammonia, the reaction is halted. 189.5 g of product
are recovered (but a portion of the losses is related to the numerous samplings during the
synthesis). The crude product is subsequently distilled under a pressure reduced to
16 mbar with a Vigreux column, which amounts to removing the heavy products. The
distillation is carried out at a temperature of 216 to 289°C in the boiler and 205 to 219°C at
the distillation column top. The whole of the product has passed in 20 minutes. 159 g of
distillate and 15.3 g of top fraction are recovered for 13 g of distillation concentrate (heavy
fraction), i.e. a distillation yield of 92%.
The product resulting from this reaction is analyzed by gas chromatography, on an
HP5890 series I1 chromatograph, with an HP5 column (30 m).
The crude product obtained comprises 0.9% by weight of palmitonitrile, 86.3% by
weight of isooleonitrile, 9.1% by weight of stearonitrile, 0.4% by weight of linoleonitrile,
0.3% by weight of eicosenonitrile and 0.3% by weight of eicosanonitrile.
Example 6: Preparation of the nitrile from the 12-hvdroxvstearic acid obtained accordinq to
example 4
The procedure is carried out as in the preceding example but starting from the
12-hydroxystearic acid obtained according to example 4. A mixture rich in isooleonitrile is
obtained, comprising 0.9% of palmitonitrile, 0.2% of linoleonitrile, 8.0% of stearic acid and
90.4% of isooleonitrile.
Example 7: Preparation of isooleic acid, obtained bv dehvdration of 12-hvdroxvstearic
acid, and preparation of the corresponding nitrile
Use is made, for this example, of the commercial 12-hydroxystearic acid of
example 5. The dehydration reaction is followed by monitoring the iodine number and the
hydroxyl number. In order to carry out this reaction, an ~mberl~s1t5@ a cid resin is used
as catalyst at a concentration of 5% by weight. At a reaction temperature of 120°C and
under a high vacuum of 400 mbar, in order to remove the water produced by the reaction,
a product having an iodine number of 68 and a hydroxyl number of 6 was obtained.
Under the same conditions and at. a temperature of 1 50°C, a zero hydroxyl number
is obtained, with an iodine number of 75.
The crude product obtained comprises 1 .O% by weight of palmitic acid, 85.2% by
weight of isooleic acid, 9.2% by weight of stearic acid, 0.3% by weight of linoleic acid,
0.3% by weight of eicosenoic acid and 0.3% by weight of eicosanoic acid.
Example 7a: Preparation of isooleic acid bv dehvdration of 12-hydroxvstearic acid and
preparation of the correspondinq nitrile
Use is made, for this example, of the commercial 12-hydroxystearic acid of
example 5. The dehydration reaction is followed by monitoring the iodine number and the
hydroxyl number. In order to carry out this reaction, a silica/alumina catalyst comprising
10% of alumina (having a specific surface of 406 m2/g) is used as catalyst at a
concentration of 10% by weight. At a reaction temperature of 180°C, under a partial
vacuum in order to remove the water produced by the reaction, a product having an iodine
number of 72 and a hydroxyl number of 6 is obtained.
Example 7b: Preparation of isooleic acid bv dehvdration of 12-hvdroxvstearic acid
Use is made, for this example, of the mixture of hydrogenated methyl esters
produced according to example 4. The dehydration reaction is followed by monitoring the
iodine number and the hydroxyl number. In order to carry out this reaction, use is made of
sulfuric acid (0.1%) and an activated clay (1 .O% by weight) as catalyst. The reaction takes
place at a temperature of 180°C for a duration of 3 hours and under a partial vacuum, inorder
to remove the water produced by the reaction. After reaction, the product is washed
and dried in order to remove the catalyst. A product having an iodine number of 55 and a
hydroxyl number of 2 is obtained.
Example 8: Preparation of isoeicosenonitrile from the 14-hvdroxveicosanoic acid resultinq
from example 2
The procedure is carried out as in example 5, starting from the 14-hydroxyeicosanoic
acid resulting from example 2, and a mixture of nitriles comprising 51% of
isoeicosenonitrile is obtained. The increase in the content of C20:l nitrile with respect to
the lesquerolic acid can be explained by the high reactivity of the polyunsaturated acids
during the conversion to nitriles, these resulting in heavy products which are removed in
the distillation concentrate.
Example 9: Preparation of isoeicosenonitrile from the 14-hvdroxveicosanoic acid resulting
from example 3
The procedure is carried out as in the preceding example 8 with the mixture rich in
14-hydroxyeicosanoic acid of example 3. A mixture of nitriles comprising 90% of
isoeicosenonitrile is obtained.
Example 10: Oxidative cleavaqe with hydrogen peroxide of the isooleonitrile resulting from
example 5
25 g of product obtained, such as in example 5, are mixed with 250 mg of tungstic
acid in a jacketed reactor. With mechanical stirring, the temperature is regulated at 70°C
and approximately 7 grams of 70% by weight hydrogen peroxide (H202) are added
dropwise over approximately 7 minutes. After a reaction time of 2 hours, the aqueous
phase is removed by separation by settling. 250 mg of tungstic acid are again added to
the organic phase and 7 g of 70% hydrogen peroxide are again added dropwise as above.
This operation is repeated after a reaction time of 4 h, 22 h, 24 h and 26 h, with a total
duration of the test of 28 hours and 42 g of H202 added.
After separation of the final fraction of aqueous phase, the organic phase is
washed with water, then dried under vacuum and analyzed by chromatography.
The composition of the mixture obtained indicates a yield of hexanoic acid of
10.4 mol%, of heptanoic acid of 12.3% by weight, of 10-cyanodecanoic acid of 13.1 % by
weight and of I I -cyanoundecanoic acid of 12.1 % by weight.
This distribution confirms that the reaction for the dehydration of 12-hydroxystearic
acid which took place during the formation of the nitrile results in the two unsaturated
isomers C18:l 6-1 1 and C18:l 6-12.
Example 11: Oxidative cleavage with hydrogen peroxide of the isooleic acid obtained in
example 7
The procedure is carried out as in example 10 but with the acid mixture rich in
isooleic acid resulting from example 7.
The yield is 8% of heptanoic acid and 7.1 % of hexanoic acid. These two acids are
the easiest to analyze and characterize oxidative cleavage of the medium. After
esterification of the mixture obtained, the quantification of the diacids produced indicates a
yield of diacids of 8.5% of undecanedioic acid and of 7.5% of dodecanedioic acid.
Example 12: Ozonolvsis of the isoeicosenonitrile obtained in example 8 and
hydroaenation of the nitrile acid (cvanoacid) obtained to aive the corresponding amino
-acid
This example illustrates the oxidative cleavage of the unsaturated nitrile resulting
from example 8 by ozonolysis to form the nitrile-acids of formulae CN-(CH2)11-COOHa nd
CN-(CH2)12-COOH.
Ozone obtained by a Ozania ozone generator is bubbled into 50 grams of a nitrile
obtained in accordance with example 8. An amount of ozone of 50 glh, at a concentration
of 6% in pure oxygen, is produced. The entire apparatus is made of glass. During this
stage, with a duration of 4 hours, the temperature of solution is kept below 30°C. In order
to carry out the conversion of the ozonide to the nitrile-acid, the temperature is first of all
raised to approximately 60°C. When the reaction for decomposition of the ozonide begins,
it is accompanied by a raise in the temperature. A stream of oxygen is continuously added
in order to maintain the temperature and in order to directly oxidize the products resulting
from the decomposition of the ozonide. The procedure is carried out over 4 hours in order
to limit the formation of decomposition products. It is important to maintain the reaction
- 23 -
temperature slightly above the temperature of the decomposition of the ozonide during
this stage. A temperature of 95°C is used in this example.
A yield of 91 mol% of a mixture of 10-cyanodecanoic acid and 11-cyanoundecanoic
acid is obtained.
15 g of nitrile-acid are dissolved in 160 g of ethanol. The solution is placed in a
stirred autoclave with 3 g of Raney nickel catalyst; 15 g of ammonia and a pressure of
110 bar of hydrogen are then added. The temperature is raised to 100°C and the pressure
increases up to 139 bar. The conditions are maintained for 4 hours. The autoclave is
cooled and the contents are filtered in order to recover the catalyst. 50 g of water are then
added and the alcohol is distilled off. The resulting solution is titrated with dilute
hydrochloric acid and the mixture of amino acids is filtered off, washed and treated under
reflux of acetone and dried.
Example 13: Ozonolvsis of the isoeicosenonitrile obtained in example 9
The procedure is carried out as in example 12. On conclusion of the ozonolysis
stage, the reaction mixture consists predominantly of heptanoic acid and hexanoic acid,
and also of cyanoacids. The heptanoic acid and hexanoic acid are removed by washing
with hot water. The cyanoacids are recovered by extraction with cyclohexane at low
temperature and recrystallization. The mixture of cyanoacids is then hydrogenated as in
example 12.

CLAIMS
1) A process for the synthesis of o-functionalized acids, characterized in that said
acids are of formula R-(CH2),-COOH, in which R represents COOH or NH2CH2 and n
represents an integer between 9 and 12, they are obtained from a feedstock of natural
origin comprising unsaturated hydroxylated fatty acids in the acid, ester or polyol ester
form comprising at least 18 carbon atoms per molecule and in that said process
comprises the following stages:
a) hydrogenation of the unsaturated hydroxylated fatty acids, resulting in saturated
hydroxylated fatty acids,
b) dehydration of the saturated hydroxylated fatty acids, resulting in monounsaturated
fatty acids,
c) oxidative cleavage at the double bond of the monounsaturated fatty acids,
resulting in an a,o-bifunctional compound from diacid or nitrile-acid.
2) The process as claimed in claim 1, characterized in that the hydrogenation stage
a) is carried out at a temperature of between 70 and 180°C, preferably 70 and 150°C,
more preferably between 90 and 130°C, under an H2 pressure of between 1 and 300 bar,
preferably between 5 and 50 bar, in the presence of either homogeneous or
heterogeneous hydrogenation catalysts. ,
3) The process as claimed in claim 2, characterized in that said catalysts are noble
metals, such as Pt, Pd or Rh, or transition metals, such as Mo, W, Cr, Fe, Co or Ni, used
alone or as a mixture, optionally in the form supported on active charcoal, on alumina and
on silica.
4) The process as claimed in claim 2 or 3, characterized in that said catalysts are
chosen from Raney nickel and/or palladium-on-active charcoal.
5) The process as claimed in one of claims 1 to 4, characterized in that the
hydrogenation stage a) is carried out under operational conditions such that the effluent
resulting from this hydrogenation stage exhibits an iodine number < 5, preferably < 3 and
more preferably < 1 and a hydroxyl number > 100 mg KOHIg.
6) The process as claimed in one of claims 1 to 5, characterized in that the stage b)
of dehydration of the saturated hydroxylated fatty acids is carried out at a temperature of
between 100 and 300°C and in the presence of an acid catalyst, preferably chosen from:
sulfuric acid, phosphoric acid, sulfonic acids, alkyl sulfonates or ion-exchange acid resins.
7) The process as claimed in one of claims 1 to 6, characterized in that the oxidative
cleavage stage c) is carried out using an oxidizing agent chosen from KMn04, hydrogen
peroxide or oxidizing ozone, optionally in combination with a catalyst, such as tungstic
acid, in particular ozone in combination with oxygen.
8) The process as claimed in one of claims 1 to 7, characterized in that it comprises
an additional intermediate stage, between stage b) and stage c), of nitrilation of the acid
functional group of the monounsaturated fatty. acid, resulting in an unsaturated nitrile.
9) The process as claimed in one of claims 1 to 7, characterized in that it comprises a
stage of nitrilation of the acid functional group of the saturated hydroxylated fatty acid
resulting from stage a) with concomitant dehydration, resulting in an unsaturated nitrile.
10) The process as claimed in either of claims 8 and 9, characterized in that the
nitrilation stage is carried out in the liquid phase or in the gas phase using ammonia at a
temperature generally of between 150°C and 350°C and with a catalyst.
11) The process as claimed in claim 10, characterized in that said nitrilation is carried
out in the liquid phase with, as catalyst, a metal oxide which is zinc oxide.
12) The process as claimed in claim 10, characterized in that said nitrilation is carried
out in the gas phase with said catalyst being supported on a fixed bed of doped or nondoped
alumina.
13) The process as claimed in one of claims 8 to 12, characterized in that the effluent
from the nitrilation stage is subjected to the oxidative cleavage stage c), the effluent
(comprising the nitrile-acid compound) of which is subjected to a hydrogenation d).
14) The process as claimed in claim 13, characterized in that said hydrogenation is
carried out at a temperature of between 70 and 200°C, preferably between 70 and 150°C
and more preferably between 90 and 130°C, under an H2 pressure of between 1 and
300 bar, preferably between 5 and 50 bar, in the presence of either homogeneous or
heterogeneous hydrogenation catalysts.
15) The process as claimed in one of claims 1 to 14, characterized in that said
o-functionalized acid is a diacid or an amino acid and in that said feedstock of natural
origin comprises unsaturated hydroxylated fattyacids in the ester form (alcohol or polyol
ester, such as glycerol ester) and in particular in the form of hydroxylated oil of
corresponding fatty acid (the oil being a glycerol ester), with said stages being:
i) hydrogenation of the hydroxylated ester, in particular the corresponding oil
ii) dehydration of the hydrogenated hydroxylated ester, in particular of the
corresponding oil
iii) hydrolysis of the hydrogenated (and dehydrated) ester, in particular of the
corresponding oil, in order to obtain the corresponding unsaturated fatty acid and
alcohol or polyol, in particular glycerol
iv) separation of the alcohol or polyol, in particular glycerol, and optionally separation
of the unsaturated fatty acid isomers
v) optionally (only in the case of nitrile), ammoniation of the unsaturated (fatty) acid in
order to obtain the corresponding unsaturated nitrile
vi) oxidative cleavage of the unsaturated nitrile or fatty acid (as the case may be)
vii) optionally, separation of the cleavage products and light acids formed
viii) optionally (case of nitrile), hydrogenation of the nitrile-acid in order to form the
corresponding amino acid
ix) separation and purification of the diacid formed or of the amino acid formed, as the
case may be.
16) The process as claimed in one of claims 1 to 14, characterized in that said
a-functionalized acid is an amino acid and in that said feedstock of natural origin
comprises unsaturated hydroxylated fatty acids in the ester (alcohol or polyol ester, such
as glycerol ester) form, in particular in the form of a hydroxylated oil (glycerol ester), and
said process comprises the sequence of the following stages:
i) hydrogenation of the hydroxylated ester, in particular of the corresponding oil
ii) hydrolysis of the hydrogenated ester, in particular of the corresponding oil, in order
to obtain the corresponding saturated fatty acid and alcohol or polyol, in particular
glycerol
iii) separation of the alcohol or polyol, in particular glycerol, with optional separation of
the saturated fatty acids from the hydroxylated fatty acids
iv) ammoniation of the saturated hydroxylated acid, with simultaneous dehydration, in
order to obtain the corresponding unsaturated nitrile
v) optionally, separation of the unsaturated nitrile isomers
vi) oxidative cleavage of the unsaturated nitrile
vii) optionally, separation of the nitrile-acid cleavage products and of the light acids
formed
viii) hydrogenation of the nitrile-acid, in order to obtain the corresponding amino acid
ix) separation and purification of the amino acid obtained.
17. The process as claimed in one of claims 1 to 14, characterized in that said.
a-functionalized acid is an amino acid via a nitrile-acid, starting from a vegetable oil
source which has a low concentration of hydroxylated acid, with a sequence of following
stages:
i) alcoholysis (in particular methanolysis) of the vegetable oil, optionally concomitant
with its extraction from the seed
ii) extraction of a fraction rich in hydroxylated acid ester
iii) hydrogenation of the hydroxylated ester
iv) optionally, hydrolysis of the hydrogenated ester in order to obtain the
corresponding fatty acid
v) ammoniation of the saturated hydroxylated acid with simultaneous dehydration
(including on ester of stage iii) or on acid of stage iv)), in order to obtain the
unsaturated nitrile
vi) optionally, separation of the unsaturated nitrile isomers
vii) oxidative cleavage of the unsaturated nitrile
i i ) optionally, separation of the nitrile-acid cleavage products and of the light acids
formed
ix) hydrogenation of the nitrile-acid in order to obtain the amino acid
x) separation and purification of the amino acid obtained.
Dated this 30.12.201 3
OF REMFRY & SAGAR
ATTORNEY FOR THE APPLICANT[S]