U.S. patent application number 10/678626 was filed with the patent office on 2004-05-13 for process for the preparation of n-phosphonomethylglycine.
Invention is credited to Oftring, Alfred, Orsten, Stefan, Wulff, Christian.
Application Number | 20040092765 10/678626 |
Document ID | / |
Family ID | 7934229 |
Filed Date | 2004-05-13 |
United States Patent
Application |
20040092765 |
Kind Code |
A1 |
Wulff, Christian ; et
al. |
May 13, 2004 |
Process for the preparation of N-phosphonomethylglycine
Abstract
The present invention relates to a process for the preparation
of N-phosphonomethylglycine by reacting a hexahydrotriazine
derivative with a triacyl phosphite. The process gives
N-phosphonomethylglycine in high yield and in a simple and
inexpensive manner.
Inventors: |
Wulff, Christian; (Mannheim,
DE) ; Orsten, Stefan; (Ellerstadt, DE) ;
Oftring, Alfred; (Bad Durkheim, DE) |
Correspondence
Address: |
KEIL & WEINKAUF
1350 CONNECTICUT AVENUE, N.W.
WASHINGTON
DC
20036
US
|
Family ID: |
7934229 |
Appl. No.: |
10/678626 |
Filed: |
October 6, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10678626 |
Oct 6, 2003 |
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10168717 |
Jun 24, 2002 |
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10168717 |
Jun 24, 2002 |
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PCT/EP00/13162 |
Dec 22, 2000 |
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Current U.S.
Class: |
562/18 |
Current CPC
Class: |
C07F 9/4093 20130101;
C07F 9/3813 20130101 |
Class at
Publication: |
562/018 |
International
Class: |
C07F 009/28 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 23, 1999 |
DE |
19962601.4 |
Claims
We claim:
1. A process for the preparation of N-phosphonomethylglycine,
wherein a) a hexahydrotriazine derivative of the formula II 10in
which X is CN, COOZ, CONR.sup.1R.sup.2 or CH.sub.2OY, Y is H or a
radical which is readily exchangable for H, Z is H, an alkali
metal, alkaline earth metal, C.sub.1-C.sub.18-alkyl or aryl, which
is unsubstituted or substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2
or OC.sub.1-C.sub.4-alkyl, R.sup.1 and R.sup.2 can be identical or
different and are H or C.sub.1-C.sub.4-alkyl, is reacted with a
triacyl phosphite of the formula IIIP(OCOR.sup.3).sub.3 (III)in
which the radicals R.sup.3, which can be identical or different,
are C.sub.1-C.sub.18-alkyl or aryl which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl, and b) the product obtained is hydrolyzed,
and, if X is CH.sub.2OY, oxidized.
2. A process as claimed in claim 1, wherein reaction of the
hexahydrotriazine derivative of the formula II with the triacyl
phosphite of the formula III gives a compound of the formula I 11in
which R.sup.3 and X have the meanings stated in claim 1.
3. A process for the preparation of a phosphono compound of the
formula I 12in which the radicals R.sup.3, which can be identical
or different, are C.sub.1-C.sub.18-alkyl or aryl which is
unsubstituted or substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl, and X us CN, COOZ, CONR.sup.1R.sup.2 or
CH.sub.2OY, Y is H or a radical which is readily exchangeable for
H; Z is H, an alkali metal, alkaline earth metal,
C.sub.1-C.sub.18-akyl or aryl, which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl; R.sup.1 and R.sup.2, which can be identical
or different, are H or C.sub.1-C.sub.4-alkyl, in which a
hexahydrotriazine derivative of the formula II 13 is reacted with a
triacyl phosphite of the formula IIIP(OCOR.sup.3).sub.3 (III) in
which R.sup.3 and X are as defined above.
4. A process as claimed in any of the preceding claims, wherein X
is CN or COOZ.
5. A process as claimed in any of the preceding claims, wherein
R.sup.3 is phenyl which is unsubstituted or substituted by
C.sub.1-C.sub.4-alkyl, NO.sub.2 or OC.sub.1-C.sub.4-alkyl, or is
CH.sub.3.
6. A process as claimed in any of the preceding claims, wherein
step (a) is carried out in an organic solvent.
7. A process as claimed in claim 6, wherein the solvent used is
dioxane or tetrahydrofuran.
8. A process as claimed in claim 6, wherein a chlorinated organic
solvent is used.
9. A process as claimed in claim 8, wherein 1,2-dichloroethane is
used as solvent.
10. A process as claimed in any of the preceding claims, wherein
the compounds of the formulae II and III in employed in essentially
equivalent amounts.
11. A process as claimed in any of the preceding claims, wherein
the compound of the formula III is prepared by reacting a
carboxylic acid of the formula IVR.sup.3COOH (IV),in which R.sup.3
has the meanings stated in claim 1 or a salt thereof with a
phosphorus trihalide.
12. A process as claimed in claim 11, wherein an alkali metal salt
or the ammonium salt of the carboxylic acid of the formula IV is
reacted with the phosphorus halide.
13. A process as claimed in claim 11, wherein the carboxylic acid
of the formula IV is reacted with the phosphorus halide in the
presence of an amine.
14. A process as claimed in claim 11, wherein the carboxylic acid
of the formula IV is reacted with the phosphorus halide in the
absence of a base.
15. A process as claimed in any of claims 11 to 14, wherein the
reaction is carried out in an inert organic solvent which is
selected from among the aromatic or aliphatic hydrocarbons and
chlorinated hydrocarbons.
16. A process as claimed in claim 15, wherein the solvent is
recovered after the reaction and recycled.
17. A process as claimed in any of claims 1, 2 or 4 to 9, wherein
the compound of the formula I is hydrolyzed with an aqueous
acid.
18. A process as claimed in claim 17, wherein the hydrolysis is
carried out in a two-phase system.
19. A process as claimed in claim 18, wherein the
phosphono-methylglycine is precipitated from the aqueous phase by
bringing the pH to a value of in the range of 0.5 to 2.0.
20. A process as claimed in claim 19, wherein the
phosphono-methylglycine is precipitated in the presence of a
solvent which is miscible with water.
21. A phosphono compound of the formula I 14in which the radicals
R.sup.3, which can be identical or different, are
C.sub.1-C.sub.18-alkyl or aryl which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl, and X is CN, COOZ, CONR.sup.1R.sup.2 or
CH.sub.2OY, Y is H or a radical which is readily exchangeable for
H; Z is H, an alkali metal, alkaline earth metal,
C.sub.1-C.sub.18-akyl or aryl, which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl; R.sup.1 and R.sup.2, which can be identical
or different, are H or C.sub.1-C.sub.4-alkyl, or a salt
thereof.
22. A compound as claimed in claim 21, wherein R.sup.3 is phenyl
which is unsubstituted or substituted by C.sub.1-C.sub.4-alkyl,
NO.sub.2 or OC.sub.1-C.sub.4-alkyl, or is methyl.
23. A compound as claimed in claim 21 or 22, wherein X is CN or
COOZ, wherein Z is H, alkali metal or C.sub.1-C.sub.18-alkyl.
24. A compound as claimed in claim 21 of the formula 15
25. An intermediate obtainable by reacting a hexahydrotriazine
derivative of the formula II 16in which X is CN, COOZ,
CONR.sup.1R.sup.2 or CH.sub.2OY, Y is H or a radical which is
readily exchangeable for H; Z is H, an alkali metal, alkaline earth
metal, C.sub.1-C.sub.18-alkyl or aryl, which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl; R.sup.1 and R.sup.2 can be identical or
different and are H or C.sub.1-C.sub.4-alkyl, is reacted with a
triacyl phosphite of the formula IIIP(OCOR.sup.3).sub.3 (III) in
which the radicals R.sup.3, which can be identical or different,
are C.sub.1-C.sub.18-alkyl or aryl which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl.
Description
[0001] The invention relates to a process for the preparation of
N-phosphonomethylglycine by reacting a hexahydrotriazine compound
with a triacyl phosphite, and to intermediates for use in this
process.
[0002] N-Phosphonomethylglycine (glyphosate) is a widely employed
nonselective herbicide. A large number of processes for the
preparation of phosphonomethylglycine are known. One possibility of
preparing it exists in reacting hexahydrotriazine derivatives with
phosphorous esters. Thus, U.S. Pat. No. 4,181,800 describes the
preparation of hexahydrotriazines of the formula: 1
[0003] and U.S. Pat. No. 4,053,505 the reaction of these
hexahydrotriazines with phosphorous diesters and subsequent
hydrolysis of the resulting product to give phosphonomethylglycine.
It has emerged that both yield and selectivity favoring the
monophosphonated product are capable of improvement. Also,
phosphorous diesters are very expensive.
[0004] EP-A-104 775 (corresponding to U.S. Pat. No. 4,425,284, U.S.
Pat. No. 4,482,504 and U.S. Pat. No. 4,535,181) describes the
reaction of the above hexahydrotriazines with an acyl halide and
the subsequent phosphonation with a phosphorous triester and
hydrolysis to give phosphonomethylglycine in accordance with the
following equation: 2
[0005] While this process gives relatively good yields of
phosphonomethylglycine, it requires not only the use of the
expensive phosphorous esters, but additionally the use of carbonyl
chloride. In addition, the carbonyl chloride might at most be
recovered in the form of the free acid and then reconverted into
the acid chloride in a separate step, which considerably increases
the costs of the process. Moreover, the alcohol with which the
phosphorous acid is esterified cannot be recycled fully since an
equivalent of the corresponding alkyl chloride, which is, moreover,
toxicologically unacceptable, is formed during the reaction.
[0006] U.S. Pat. No. 4,428,888 (corresponding to EP-A-149 294)
describes the reaction of the abovementioned hexahydrotriazine with
a phosphorous acid chloride in the presence of a strong anhydrous
acid, for example hydrogen chloride, and a
C.sub.1-C.sub.6-carboxylic acid, such as acetic acid. In this
manner, a large number of undefined by-products are obtained, and
these reduce the phosphonomethylglycine yield and necessitate
complicated purification of the product.
[0007] U.S. Pat. No. 4,442,044 describes the reaction of a
hexahydrotriazine of the formula 5 with a phosphorous acid triester
to give the corresponding phosphonate compound, which is used as
herbicide.
[0008] DD-A-141 929 and DD-A-118 435 describe the reaction of an
alkali metal salt of the above hexahydrotriazine (R=for example Na)
with a phosphorous diester. However, since alkali salts are
sparingly soluble, the conversion rate is only low.
[0009] U.S. Pat. No. 5,053,529 describes the preparation of
phosphonomethylglycine by reacting the above hexahydrotriazines
with phosphorous triesters in the presence of titanium
tetrachloride, followed by hydrolysis of the product obtained. The
use of titanium tetrachloride makes the preparation considerably
more expensive. Moreover, the phosphonomethylglycine yields are
unsatisfactory.
[0010] U.S. Pat. No. 4,454,063, U.S. Pat. No. 4,487,724 and U.S.
Pat. No. 4,429,124 describe the preparation of
phosphonomethylglycine by reacting a compound of the formula 3
[0011] in which R.sup.1 and R.sup.2 are aromatic or aliphatic
groups with RCOX (X=Cl, Br, I) to give a compound of the formula
4
[0012] reaction of this product with a metal cyanide and hydrolysis
of the product obtained. The disadvantages of this method are
stated as above in relation to the use of the acid chloride.
[0013] Other possible syntheses which have been described are based
on the cyanomethyl-substituted hexahydrotriazine of the formula.
5
[0014] U.S. Pat. No. 3,923,877 and U.S. Pat. No. 4,008,296 disclose
the reaction of this hexahydrotriazine derivative with a dialkyl
phosphonate in the presence of an acidic catalyst such as hydrogen
chloride, a Lewis acid, a carbonyl chloride or a carboxylic
anhydride to give a compound of the formula: 6
[0015] Subsequent hydrolysis yields the phosphonomethylglycine, 8
to 10% of the diphosphonomethylated product being formed.
[0016] U.S. Pat. No. 4,067,719, U.S. Pat. No. 4,083,898, U.S. Pat.
No. 4,089,671 and DE-A-2751631 describe the reaction of
cyanomethyl-substituted hexahydrotriazine with a diaryl phosphonate
in the absence of a catalyst to give a compound 9 where R"=aryl.
This method has the same disadvantages as described above for the
use of the carboxyl-substituted hexahydrotriazine 5.
[0017] EP-A-097 522 (corresponding to U.S. Pat. No. 4,476,063 and
U.S. Pat. No. 4,534,902) describes the reaction of the
hexahydrotriazine 6 with an acyl halide to give 10, the subsequent
phosphonation with a phosphorous triester or diester to give 11 and
finally the hydrolysis to phosphonomethylglycine as described in
the following equation: 7
[0018] The disadvantages are the same as for the processes in which
the carboxyl-substituted hexahydrotriazine derivatives are
used.
[0019] Finally, U.S. Pat. No. 4,415,503 describes the reaction of
the cyanomethyl-substituted hexahydrotriazine in a manner which is
similar to the process described in U.S. Pat. No. 4,428,888. Again,
substantial formation of by-products can be observed.
[0020] EP 164 923 A describes an improved hydrolysis of a compound
of the formula 11.
[0021] It is an object of the present invention to provide a simple
and economical process for the preparation of
phosphonomethylglycine in which the phosphomethylglycine is
additionally obtained in high purity.
[0022] We have found that this object is achieved by reacting a
hexahydrotriazine derivative with a triacyl phosphite and
subsequently hydrolyzing the product obtained to give
phosphonomethylglycine.
[0023] The present invention therefore relates to a process for the
preparation of N-phosphonomethylglycine, wherein
[0024] a) a hexahydrotriazine derivative of the formula II 8
[0025] in which X is CN, COOZ, CONR.sup.1R.sup.2 or CH.sub.2OY,
[0026] Y is H or a radical which is readily exchangable for H,
[0027] Z is H, an alkali metal, alkaline earth metal,
C.sub.1-C.sub.18-alkyl or aryl, which is unsubstituted or
substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl,
[0028] R.sup.1 and R.sup.2 can be identical or different and are H
or C.sub.1-C.sub.4-alkyl,
[0029] is reacted with a triacyl phosphite of the formula III
P(OCOR.sup.3).sub.3
[0030] in which the radicals R.sup.3, which can be identical or
different, are C.sub.1-C.sub.18-alkyl or aryl which is
unsubstituted or substituted by C.sub.1-C.sub.4-alkyl, NO.sub.2 or
OC.sub.1-C.sub.4-alkyl,
[0031] to give a compound of the formula I 9
[0032] in which R.sup.3 and X have the abovementioned meanings
and
[0033] b) the compound of the formula I is hydrolyzed, and, if X is
CH.sub.2OY, oxidized.
[0034] Furthermore, the invention relates to the compounds of the
formula I and their preparation in accordance with step a) of the
process for the preparation of phosphonomethylglycine.
[0035] Alkyl is a linear or branched alkyl chain having preferably
1 to 8 carbon atoms and in particular 1 to 4 carbon atoms. Examples
of alkyl are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl,
sec-butyl, t-butyl, n-hexyl, 2-ethylhexyl, etc.
[0036] Aryl is preferably phenyl and naphthyl.
[0037] X is preferably CN or COOZ.
[0038] Z is preferably H, alkali metal or
C.sub.1-C.sub.18-alkyl.
[0039] If Y represents a radical which is readily exchangable for
H, this preferably takes the form of an aliphatic or aromatic acyl
radical or C.sub.1-C.sub.6-alkyl group. The aliphatic acyl radical
is preferably a C.sub.1-C.sub.6-CO radical, and the aromatic acyl
radical preferably takes the form of the benzoyl radical.
[0040] R.sup.1 and R.sup.2 are preferably H.
[0041] The radical R.sup.3 especially preferably takes the form of
an aryl radical which can be unsubstituted or substituted as stated
above. Especially suitable radicals R.sup.3 are phenyl, p-tolyl and
p-nitrophenyl.
[0042] The compounds of the formula II are known and can be
prepared in the known manner or analogously to known processes,
see, for example, the state of the art mentioned at the outset. For
example, an amine X--CH.sub.2--NH.sub.2 can be reacted with a
formaldehyde source, such as aqueous formalin solution or
paraformaldehyde, for example by dissolving the primary amine in
the aqueous formalin solution. The desired hexahydrotriazine can
subsequently be obtained by crystallization or evaporation of the
water. This process is described in DE-A-2645085 in accordance with
U.S. Pat. No. 4,181,800, whose full extent is referred to
herewith.
[0043] The compound of the formula II in which X is CN can be
obtained by Strecker synthesis, i.e. by reacting ammonia,
hydrocyanic acid and a formaldehyde source. Such a process is
described, for example, in U.S. Pat. No. 2,823,222, whose full
extent is referred to herewith.
[0044] The compounds of the formula III can be prepared by a
plurality of processes. A first possibility is to react a salt of a
carboxylic acid R.sup.3COOH with a phosphorus trihalide, in
particular phosphorus trichloride. The carboxylate used is
preferably an alkali metal salt or alkaline earth metal salt, in
particular the sodium, potassium or calcium salt, or the ammonium
salt. This reaction can be carried out without using a solvent, and
the reaction product obtained can be used directly in step (a).
However, the process is preferably carried out in an inert organic
solvent, in particular in an ether such as dioxane, tetrahydrofuran
and the like, a halogenated, in particular a chlorinated or
fluorinated, organic solvent such as dichloromethane,
1,2-dichloroethane, 1,2-dichloropropane, 1,1,1-trichloroethane,
1,1,2-trichloroethane, 1,1,2,2-tetra-chloroethane, chlorobenzene or
1,2-dichlorobenzene, an aliphatic or aromatic hydrocarbon such as
n-octane, toluene, xylene or nitrobenzene. It is preferred to use
the same solvent as subsequently in step (a). Especially preferred
is the use of a chlorinated hydrocarbon.
[0045] The salt formed during the reaction, for example sodium
chloride when using phosphorus trichloride and the sodium salt of
the carboxylic acid employed, can be eliminated after the reaction.
If ammonium chloride or another ammonium halide is obtained as the
salt, the ammonia employed can be recovered by basifying (pH 11-14)
an aqueous solution of the salt with a strong base, for example
sodium hydroxide solution, and subsequently stripping the ammonia
in the customary manner. The ammonia obtained in this manner can be
recirculated after drying, for example by distillation in the
liquid or gaseous state, or as aqueous solution, and used for
preparing the ammonium salt of the carboxylic acid.
[0046] Another possibility of preparing the compounds of the
formula III is to react a carboxylic acid R.sup.3COOH with the
phosphorus trihalide in the presence of an amine. Amines which are
used are, in particular, aliphatic or cycloaliphatic di- or
triamines, such as triethylamine, tributylamine, dimethylethylamine
or dimethyl-cyclohexylamine, and pyridine. In general, such a
procedure is carried out in an organic solvent. Suitable solvents
are stated above in connection with the first possibility for
preparation. Dioxane, 1,2-dichloropropane, 1,2-dichloroethane,
nitrobenzene or toluene are preferably used. When using a solvent,
the amine hydrochloride formed precipitates and can be removed by
filtration. If the amine hydrochlorides are treated with a strong
base, for example with aqueous sodium hydroxide solution, the
amines are set free from the hydrochloride. Volatile amines can
then be recovered by distillation or extraction. Nonvolatile amines
can be recovered by extraction or, if a two-phase mixture is
obtained when the amine is set free, by phase separation. Solid
amines can be recovered by filtration. The amines recovered can be
recirculated into the process, if appropriate after drying.
[0047] Another possibility of preparing the compounds of the
formula III is to react the carboxylic acid R.sup.3COOH with a
phosphorus trihalide, in particular phosphorus trichloride, without
addition of a base. In this reaction, the hydrogen halide which
forms must be removed from the reaction mixture. This can be done
in the customary fashion, for example by passing through an inert
gas, such as nitrogen. The hydrogen halide which has been set free
can then be used for the hydrolysis in step (b) in the form of an
aqueous solution.
[0048] Step (a) of the process according to the invention can be
carried out with or without solvent, for example in the melt.
However, it is preferred to use an inert organic solvent, for
example a hydrocarbon such as toluene or xylene, an ether such as
tetrahydrofuran, dioxane or dibutyl ether, nitrobenzene and the
like. It is especially preferred to carry out the process in a
halogenated solvent, in particular a chlorinated, preferably a
chlorinated and/or fluorinated aliphatic hydrocarbon, such as
dichloromethane, 1,2-dichloroethane, 1,2-dichloropropane,
1,1,1-trichloroethane, 1,1,2-trichloroethane,
1,1,2,2-tetra-chloroethane, chlorobenzene or 1,2-dichlorobenzene.
The reactants are expediently employed in essentially
stoichiometric amounts. However, an excess of, for example, up to
10% of one or the other reactant may also be used. In general, the
reaction temperature is in the range of -10.degree. C. to
140.degree. C., preferably in the range of room temperature to
100.degree. C. Only short reaction times are required under these
conditions; in general, the reaction is essentially complete after
10 to 30 minutes.
[0049] The compounds of the formula I obtained in accordance with
step (a) are useful intermediates for preparing
phosphonomethylglycine. To this end, the compounds of the formula I
are hydrolyzed. The hydrolysis can take the form of an acid or
alkaline hydrolysis, preferably an acid hydrolysis. Acids which are
used are, in particular, inorganic acids such as hydrochloric acid,
sulfuric acid or phosphoric acid. Alkaline hydrolysis is generally
carried out using an alkali metal hydroxide or alkaline earth metal
hydroxide, in particular using sodium hydroxide or potassium
hydroxide.
[0050] The hydrolysis is expediently carried out with an aqueous
acid or base. In general, the aqueous acid or base is added to the
reaction mixture obtained in step (a). The hydrolysis can be
carried out without solvent or in the presence of an inert organic
solvent which is fully or in part or not miscible with water. The
solvent employed in step (a) is preferably used. When using a
solvent in step (a), the reaction mixture obtained in step (a) is
expediently employed directly, if appropriate after removing, for
example by distillation, some of the solvent. As an alternative,
the solvent used in step (a) is removed completely and the residue
is hydrolyzed. The solvent recovered from the reaction mixture can
be reused in the preparation of the compounds of the formula III or
in step (a).
[0051] It is especially preferred to carry out the hydrolysis in a
two-phase system (aqueous phase/organic phase). Here, an organic
solvent which is miscible in part with water or not miscible with
water is used, preferably a hydrocarbon such as toluene or xylene,
an ether such as dibutyl ether and in particular a halogenated
hydrocarbon such as stated above as solvent for step (a).
Hydrolysis is carried out with intimate mixing of the two phases
using customary devices, for example stirred reactors, circulating
reactors or, preferably, static mixers. After hydrolysis has ended,
the phases are separated and processed as described below.
[0052] An especially preferred embodiment is a process in which
step (a) is carried out in a halogenated solvent, some of the
solvent is removed, if appropriate, and the resulting compound of
the formula I is hydrolyzed by treating the reaction mixture
obtained in step (a) with an aqueous acid or base.
[0053] As an alternative, the compound of the formula I can also be
hydrolyzed into phosphonomethylglycine by enzymatic means, for
example using an esterase or a nitrilase.
[0054] The acid or base is used in at least equivalent amounts, but
preferably in excess, in particular in an amount of .gtoreq.2
equivalents.
[0055] The temperature at which the hydrolysis is carried out is
generally in the range of approximately 10.degree. C. to
180.degree. C., preferably 20 to 150.degree. C.
[0056] If X is CH.sub.2OY, the product obtained after hydrolysis
still requires oxidation. The starting compound is, in particular,
one in which X is CH.sub.2OH. The oxidation to give
phosphonomethylglycine is carried out in the customary manner which
is known to the skilled worker, for example by catalytic
dehydration with copper catalysis.
[0057] If X is CH.sub.2OY and Y is an acyl radical, hydrolysis of
the product of step a) involves elimination of the acyl radical
with formation of the corresponding compound where X=CH.sub.2OH.
This is oxidized as stated above to give
phosphonomethylglycine.
[0058] If X is CH.sub.2OY and Y is an alkyl radical, ether cleavage
normally takes place simultaneously under the conditions of an acid
hydrolysis of the product of step a). The compound obtained where
X=CH.sub.2OH is oxidized as stated above to give
phosphonomethylglycine.
[0059] The phosphonomethylglycine obtained when hydrolyzing using
an excess of acid or base is dissolved in the aqueous phase. The
carboxylic acid R.sup.3COOH is formed directly when hydrolyzing
with an excess of acid or, when hydrolyzing with a base, after
acidification with a strong acid, preferably to a pH of <0.5.
The carboxylic acid is then removed in the customary manner, for
example by filtration of the carboxylic acid which has precipitated
in solid form, distillation or extraction with an organic solvent
which is not miscible with the aqueous phase. If hydrolysis is
biphasic, the carboxylic acid is present in dissolved form in the
organic phase, if appropriate. The carboxylic acid is then removed
by separating off the organic phase and, if desired, can be
recovered therefrom in the customary manner. It is obtained in high
purity and can be recycled without problems for the preparation of
the compound of the formula III. The solvent which forms the
organic phase can be recirculated and reused in the preparation of
the compounds of the formula III or in step (a). In general,
however, the solvent is previously subjected to distillation,
extraction, filtration and/or stripping in order to remove
contaminants such as alcohols, phenols, ammonium salts and/or
carboxylic acids which are soluble or insoluble in water.
[0060] The phosphonomethylglycine can be precipitated by bringing
the aqueous phase to a pH in the region of 0.5 to 2.0, in
particular 0.8 to 1.5, for example by adding an acid or base, for
example HCl, H.sub.2SO.sub.4 or NaOH, KOH, Ca(OH).sub.2 and
obtained in the customary manner, if appropriate by concentrating
the aqueous phase and/or addition of a precipitant, for example by
filtration. A solvent which is miscible with water, such as
methanol, ethanol, isopropanol, acetone and the like, is preferably
used as precipitant. The solvents can be recovered from the mother
liquor by distillation and reused.
[0061] Ammonia or ammonium chloride formed during the hydrolysis
can be recirculated into the process, if appropriate by basifying
the mixture and recovering the ammonia by stripping.
[0062] If required, the phosphonomethylglycine obtained can be
decolorized in the customary manner. This can be done for example
by treating it with small amounts of a decolorizing agent, for
example oxidants such as perborates or H.sub.2O.sub.2 or adsorbents
such as active charcoal. The amount of decolorizing agent depends
on the degree of the discoloration and can be determined in a
simple manner by the skilled worker. The treatment with the
decolorizing agent can be performed at any point after hydrolysis
and in the customary manner. It is expedient to add the
decolorizing agent before precipitating the
phosphonomethylglycine.
[0063] The process according to the invention, or each step on its
own, can be carried out continuously, discontinuously or as a
semi-batch process. Reaction vessels which are customary for such
purposes are used, such as stirred reactors or tubular reactors, if
appropriate with mixing devices arranged upstream or with mixing
elements integrated into the tubular reactor.
[0064] The process according to the invention is thus distinguished
by simple process control and inexpensive feed stocks. Only an
inorganic chloride is produced as waste product, and the protective
groups, viz. the actyl radicals of the triacyl phosphite of the
formula III, can be recycled in a simple manner. The process yields
phosphonomethylglycine in very short reaction times and high yields
of >90% of hexahydrotriazine of the formula II.
[0065] The examples which follow illustrate the invention without
imposing any limitation.
EXAMPLE 1
[0066] 0.2 mol of sodium benzoate are introduced into 50 ml of
1,4-dioxane at room temperature with the exclusion of moisture.
0.0667 mol of phosphorous trichloride are added dropwise, and
stirring of the reaction is continued for 20 minutes at 85.degree.
C. (colorless suspension). 0.0222 mol of the hexahydrotriazine 6
are added, and the reaction is stirred for a further 20 minutes at
85 to 90.degree. C. (thin suspension, readily stirrable). The
dioxane is subsequently distilled off in vacuo at 40.degree. C. 100
ml of concentrated hydrochloric acid are added to the residue and
the mixture is refluxed for 4 hours. After cooling, the benzoic
acid is filtered off, washed (with a little cold water) and
dried.
[0067] The combined filtrates are evaporated to dryness. To isolate
the phosphonomethylglycine, the residue is taken up in a little
water and precipitated by adding cold NaOH to pH=1.5. Complete
precipitation is achieved by adding a little methanol. The
phosphonomethylglycine is filtered off and dried.
[0068] Yield: 10.3 g of phosphonomethylglycine (purity 95.3%
according to HPLC), corresponding to 91% yield based on PCl.sub.3.
The crystallization mother liquor still contains 1.8% by weight of
phosphonomethylglycine.
EXAMPLE 2
[0069] 0.2 mol of sodium benzoate are introduced into 50 ml of
1,4-dioxane at room temperature with the exclusion of moisture.
0.0667 mol of phosphorous trichloride are added dropwise, and
stirring of the reaction is continued for 20 minutes at 85.degree.
C. (colorless suspension). The reaction is filtered with the
exclusion of moisture and the residue is washed with a little
dixoane. 0.0222 mol of the hexahydrotriazine 6 are added to the
filtrate, still with exclusion of moisture, and the reaction is
stirred for a further 20 minutes at 85 to 90.degree. C. The dioxane
is subsequently distilled off in vacuo at 40.degree. C. 100 ml of
concentrated hydrochloric acid are added to the residue and the
mixture is refluxed for 4 hours. After cooling, the benzoic acid is
filtered off, washed (with a little cold water) and dried.
[0070] The combined filtrates are evaporated to dryness. To isolate
the phosphonomethylglycine, the residue is taken up in a little
water and precipitated by adding cold NaOH to pH=1.5. Complete
precipitation is achieved by adding a little methanol. The
phosphonomethylglycine is filtered off and dried.
[0071] Yield: 10.5 g of phosphonomethylglycine (purity 94.1%
according to HPLC), corresponding to 93% yield based on PCl.sub.3.
The crystallization mother liquor still contains 1.9% by weight of
phosphonomethylglycine.
EXAMPLE 3
[0072] A solution of 0.12 mol of triacetyl phosphite in 50 ml of
dioxane is added at room temperature to a solution of 0.04 mol of
the hexahydrotriazine 6 in 80 ml of dioxane. Stirring of the
solution is continued for 2 hours at 100.degree. C. The solvent is
subsequently distilled off at 40.degree. C., first under
atmospheric pressure and then in vacuo. 100 ml of concentrated
hydrochloric acid are added to the residue and the reaction is
refluxed for 4 hours. The reaction mixture is evaporated to
dryness. To isolate the phosphonomethylglycine, the residue is
taken up in a little water and precipitated by adding cold NaOH to
pH=1.5. Complete precipitation is achieved by adding a little
methanol. The phosphonomethylglycine is filtered off and dried.
[0073] Yield: 15.4 g of phosphonomethylglycine (purity 98.7%
according to HPLC), corresponding to 76% yield based on PCl.sub.3.
The crystallization mother liquor still contains 1.6% by weight of
phosphonomethylglycine.
EXAMPLE 4
[0074] 284 g of ammonium benzoate in 1000 ml of 1,2-dichloroethane
are introduced into a stirred 2-l-flask equipped with a teflon
blade mixer and a reflux condenser, and 91.5 g of phosphorus
trichloride are added dropwise under a nitrogen atmosphere in the
course of 30 minutes. During this, the temperature climbs to a
maximum of 36.degree. C. Stirring is subsequently continued for 30
minutes at 25 to 36.degree. C. The mixture is filtered through a
pressure filter, and the filter cake is washed twice more with two
500 g portions of dichloroethane under nitrogen (2054 g of
filtrate).
[0075] The filtrate is introduced at room temperature into a
stirred 2-l-flask equipped with a teflon blade mixer and a reflux
condenser. The stirred filtrate is heated to 80.degree. C. in the
course of 30 minutes, and stirring is continued for 30 minutes at
80.degree. C. The solution is left to cool and is hydrolyzed
directely thereafter.
[0076] To this end, the feedstock is metered at 130.degree. C. and
8 bar into a tubular reactor (approx. volume 600 ml) with a static
mixer arranged upstream (1265 g/h of the dichloroethane solution
from the preceding step, 207 g/h 20% strength HCl). The residence
time is 30 minutes. The first runnings are discarded. For
processing, the resulting two-phase mixture is collected for 60
minutes. The phases are separated at 60.degree. C. and the aqueous
phase is extracted twice with two 100 g portions of
dichloroethane.
[0077] The dichloroethane, which is still present in the aqueous
phase, is first stripped at 60.degree. C. in a round-bottomed flask
equipped with a teflon blade stirrer by passing in nitrogen. Then,
the pH is brought to 1.0 at 40 to 60.degree. C. in the course of 15
minutes, using 50% strength sodium hydroxide solution. Stirring of
the resulting suspension is continued for 3 hours at 40.degree. C.,
the mixture is left to cool to room temperature, and the product
which has precipitated is filtered off with suction and
subsequently washed with 150 g of ice-water. The resulting solid is
dried for 16 hours at 70.degree. C. and 50 mbar.
[0078] Yield: 54.6 g of phosphonomethylglycine (purity according to
HPLC: 96.2%), which corresponds to 80% yield based on PCl.sub.3.
The crystallization mother liquor still contains 2.1% by weight of
phosphonomethylglycine.
EXAMPLE 5
[0079] A saturated solution in water is prepared from the ammonium
chloride residue of the tribenzoyl phosphite synthesis as described
in Example 4. This saturated solution is combined with the mother
liquor from the crystallization of the phosphono-methyglycine as
described in Example 4 and brought to pH 14 with excess sodium
hydroxide solution. Then, ammonia is stripped from the reaction
mixture using nitrogen and collected for gas analysis by means of
GC (purity 99%). The combined dichloroethane phases from the
hydrolysis are dried by distilling off the azeotrope
dichloroethane/water. Dry ammonia is passed into the dichloroethane
until all of the benzoic acid has been reacted to give ammonium
benzoate, and the resulting suspension of ammonium benzoate in
1,2-dichloroethane is returned into the synthetic procedure.
[0080] Yield (first recycling): 54.0 g of phosphonomethylglycine
(purity 97.0% according to HPLC) corresponds to 79% yield based on
PCl.sub.3. Yield (second recycling): 55.1 g of
phosphonomethylglycine (purity 95.5% according to HPLC) corresponds
to 81% yield based on PCl.sub.3.
EXAMPLE 6
[0081] The reaction is carried out as described in Example 4,
except that nitrobenzene is used as solvent instead of
1,2-dichloromethane.
[0082] Yield: 56.2 g of phosphonomethylglycine (purity according to
HPLC: 97.4%), which corresponds to 82% yield based on PCl.sub.3.
The crystallization mother liquor still contains 2.0% by weight of
phosphonomethylglycine.
EXAMPLE 7
[0083] The reaction is carried out as described in Example 4,
except that 1,2-dichloropropane is used as solvent instead of
1,2-dichloroethane.
[0084] Yield: 54.0 g of phosphonomethylglycine (purity according to
HPLC: 96.92%), which corresponds to 79% yield based on PCl.sub.3.
The crystallization mother liquor still contains 2.1% by weight of
phosphonomethylglycine.
EXAMPLE 8
[0085] The reaction is carried out as described in Example 1,
except that 1,2-dichloroethane is used as solvent instead of
dioxane. The phosphonomethylglycine yield is 75%.
EXAMPLE 9
[0086] The reaction is carried out as described in Example 1,
except that toluene is used as solvent instead of dioxane. The
phosphonomethylglycine yield is 68%.
EXAMPLE 10
Preparation of the Phosphite from Carboxylic Acid, Amine and
PCl.sub.3
[0087] 0.05 mol of phosphorus trichloride in 15 ml of toluene is
added dropwise at 0.degree. C. to a solution of 0.15 mol of benzoic
acid and 0.15 mol of dimethylcyclohexylamine in 90 ml of toluene.
Stirring is continued for 15 minutes at 0.degree. C. and the
mixture is subsequently allowed to come to room temperature. The
hydrochloride which has precipitated is filtered through a pressure
filter with exclusion of moisture. The tribenzoyl phosphite is
characterized via analysis of the filtrate by .sup.1H NMR and
.sup.31P NMR (yield: 99%). If the residue obtained from the
filtrate after the toluene has been distilled off is added to 0.15
mol of 10% strength NaOH, dimethylcyclohexylamine can be recovered
quantitatively by phase separation followed by extraction with
toluene. The solution is subsequently dried by removing the water
azeotropically and can be reused.
EXAMPLE 11
[0088] 0.2 mol of sodium benzoate are added to 50 ml of 1,4-dioxane
at room temperature with exclusion of moisture. 0.0667 mol of
phosphorus trichloride is added dropwise and stirring of the
mixture is continued for 20 minutes at 85.degree. C. (colorless
suspension). 0.0222 mol of the hexahydrotriazine 1 (X=CN) is added,
and stirring of the mixture is continued for another 20 minutes at
85-90.degree. C. (thin suspension, readily stirrable). The dioxane
is subsequently distilled off in vacuo at 40.degree. C. 100 ml of
concentrated hydrochloric acid are added to the residue and the
mixture is refluxed for 4 hours. When cold, the benzoic acid is
filtered off and washed (a little cold water). The combined
filtrates are extracted twice with in each case 30 ml of toluene,
evaporated to dryness on a rotary evaporator and rotary-evaporated
three more times with ethanol to remove excess hydrochloric acid.
The toluene phase is concentrated and the residue is combined with
the benzoic acid which has been recovered.
[0089] To isolate the phosphonomethylglycine from the residue of
the aqueous phase, this may now be taken up in a little water and
precipitated cold at pH 1.0 (addition of NaOH). Complete
precipitation is achieved by adding a little methanol, which is
recovered from the mother liquor by distillation. Yield: 91%.
[0090] The benzoic acid which has been recovered (0.2 mol,
purity>99% according to HPLC) is dissolved in 0.2 mol of 5%
strength NaOH, the water is subsequently distilled off and the
residue is dried. The resulting sodium benzoate together with the
dioxane which has been recovered is reused in the synthetic
procedure.
[0091] Yield (first recycling): 90% Yield (second recycling): 84%
Yield (third recycling): 88%.
* * * * *