EP1401847A1 - Procede pour la production d'acides $g(a)-aminophosphoniques - Google Patents

Procede pour la production d'acides $g(a)-aminophosphoniques

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Publication number
EP1401847A1
EP1401847A1 EP02780837A EP02780837A EP1401847A1 EP 1401847 A1 EP1401847 A1 EP 1401847A1 EP 02780837 A EP02780837 A EP 02780837A EP 02780837 A EP02780837 A EP 02780837A EP 1401847 A1 EP1401847 A1 EP 1401847A1
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EP
European Patent Office
Prior art keywords
alkyl
aryl
acid
formula
alkenyl
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EP02780837A
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German (de)
English (en)
Inventor
Christian Wulff
Stefan Orsten
Alfred Oftring
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BASF SE
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BASF SE
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/409—Compounds containing the structure P(=X)-X-acyl, P(=X) -X-heteroatom, P(=X)-X-CN (X = O, S, Se)
    • C07F9/4093—Compounds containing the structure P(=X)-X-C(=X)- (X = O, S, Se)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
    • C07F9/3813—N-Phosphonomethylglycine; Salts or complexes thereof

Definitions

  • the invention relates to a process for the preparation of ⁇ -aminophosphonic acids by reacting special hexahydrotriazine compounds with triorganyl phosphites and to intermediates for use in this process.
  • ⁇ -Aminophosphonic acids are compounds that are of great technical importance. They are used, for example, as agrochemicals, as described in DE 25 57 139, EP 480 307, as pharmaceutical intermediates, as described in US Pat. No. 5,521,179, as flame retardants, as described in DE 25 00 428, as dye intermediates, as described in EP 385 014, or as a gelate former, as described in DE 25 00 428.
  • No. 4,442,044 describes the reaction of a hexahydrotriazine of the formula 5 with a phosphorous triester to give the corresponding phosphonate compound, which is used as a herbicide.
  • No. 5,053,529 describes the production of phosphonomethylglycine by reacting the above hexahydrotriazines with phosphoric acid triggers in the presence of titanium tetrachloride and subsequently eats saponification of the product obtained.
  • the use of titanium tetrachloride significantly increases the cost of production.
  • the yields of phosphonomethylglycine are unsatisfactory.
  • EP-A-097 522 (corresponding to US 4,476,063 and US 4,534,902) describes the reaction of hexahydrotriazine 6 with an acyl halide to 10, subsequent phosphonation with a phosphoric acid triester or diester to 11 and finally saponification to phosphonomethylglycine according to the following reaction:
  • US 4,415,503 describes the reaction of the cyanomethyl-substituted hexahydrotriazine analogously to the process described in US 4,428,888. The increased formation of by-products can also be observed in this case.
  • EP 164 923 A describes an improved hydrolysis of a compound of the formula 11.
  • Glyphosate can also be obtained on the route via diketopiperazine.
  • Diketopiperazine is a simply protected glycine derivative and is therefore a potential educt which is a special enables simple phosphonomethylation.
  • the synthetic route via this compound has three major disadvantages: on the one hand only phosphonomethylglycine is accessible, on the other hand the synthesis of diketopiperazine is difficult and yields poor yields (Curtius et al., J. Prakt. Chem. 1988, 37, 176; Schöllkopf et al., Liebigs Ann. Chem.
  • Protecting groups are often used to force simple phosphonomethylation. Examples are the use of CO 2 (US 4,439,373), benzyl (US 4,921,991), carbamates (US 4,548,760), hydroxylamines (Pastor, Tetrahedron 1992, 48 (14), 45 2911), silyl (Courtois, Synth. Commun. 1991, 21 (2), 201).
  • CO 2 US 4,439,373
  • benzyl US 4,921,991
  • carbamates US 4,548,760
  • hydroxylamines Pastor, Tetrahedron 1992, 48 (14), 45 2911
  • silyl Courtois, Synth. Commun. 1991, 21 (2), 201).
  • the use of a protective group always requires two additional synthetic steps, namely the introduction and the removal of the protective group, which is always unfavorable for economic reasons, especially when the protective group cannot be recycled.
  • N-formylaminomethylphosphonic acid For the synthesis of N-formylaminomethylphosphonic acid, one can start from formamide according to EP 98159, convert it with formaldehyde into the corresponding methylol and then phosphonate with triethyl phosphite. As described above, this process leads to two problems: firstly, the use of expensive phosphite and secondly, poor yields in the phosphonomethylation of amides. An analogous implementation using benzamide is possible (US 5,041,627, WO 92/03448). Both N-benzoyl and N-formylaminomethylphosphonic acid can then be saponified to free aminomethylphosphonic acid.
  • N-acylaminomethylphosphonic acid derivatives are run through when using hexahydrotriazines as intermediates for the aminomethylphosphonic acid synthesis.
  • N-acyl triazines can be reacted with poor yields in acetic acid with PC1 (Soroka, Synthesis 1989, 7, 547).
  • this process provides a large amount of undesirable by-products such as bis (chloroethyl ether), acetyl chloride and acetic anhydride, which must be separated and possibly disposed of.
  • the use of the comparatively expensive phosphites slightly increases the yield. Good yields can be achieved if catalysts such as BF 3 are additionally used (Maier, Phosphorus, Sulfur, and Silicon 1990, 47, 361).
  • X represents CN, COOZ, CONR i R 2 or CH 2 OY,
  • Y is H or a residue that is easily interchangeable with H
  • Z represents H, an alkali metal, alkaline earth metal, Ci-Cig-alkyl or aryl, which is optionally substituted by C 1 -C 4 alkyl, N0 2 or OC 1 -C alkyl;
  • R 1 and R 2 which may be the same or different, for H or
  • radicals R 3 which may be the same or different, represent -C 18 alkyl or aryl, which is optionally substituted by -C 4 alkyl, N0 2 or OC ⁇ -C alkyl,
  • Step (a) of the process is preferably carried out in an inert organic solvent.
  • the hydrolysis of the reaction product either takes place in an aqueous / organic two-phase system, or the solvent used in step (a) is distilled off before the hydrolysis.
  • the problem with synthesis is frequently that exactly one phosphonomethyl group has to be introduced on a primary nitrogen atom.
  • syntheses should start from inexpensive starting materials and cause low manufacturing costs, but should deliver products that are as pure as possible.
  • the present invention is therefore based on the object of providing a simple and inexpensive process for the preparation of ⁇ -aminophosphonic acids, in which the product is also obtained in high purity.
  • the present invention therefore relates to a process for the preparation of ⁇ -aminophosphonic acids of the formula I:
  • R 1 has the meanings given for R 2 , except CH 2 C0 2 H,
  • R 2 is C 1 -C 20 o-alkyl, C 2 -C 2 oo-alkenyl, C 3 -C 10 -cycloalkyl, C 3 -C 12 heterocyclyl, aryl, N (R) 2 or OR 4 ,
  • each alkyl, alkenyl, cycloalkyl, heterocyclyl and aryl radical may have 1, 2, 3 or 4 substituents which are independently selected from Ci-Ci ⁇ -alkyl, C 3 -C 10 heterocyclyl, C0 2 R 5 , C0 2 M, SO 3 R 5 , S0 3 M, HP0 (0H) 0R 5 , HP0 (0H) 0M, CN, N0 2 , halogen, CONR 6 R 7 , NR 6 R 7 , alkoxyalkyl, Ha- logenalkyl, OH, OCOR 5 , NR 6 COR 5 unsubstituted aryl and substituted aryl which has one or two substituents which are selected independently of one another from C 1 -C 0 -alkyl, Alkoxy, halogen, N0 2 , NH 2 , OH, C0 2 H, C0 2 alkyl, OCOR 5 and
  • R 4 are hydrogen, C 2 is o-alkyl, C 2 -C 20 alkenyl, C 3 -C ⁇ 0 -Cy- cloalkyl or aryl,
  • R 5 represents hydrogen, Ci-Ci ⁇ -alkyl, aryl or arylalkyl
  • M stands for a metal cation
  • R 6 and R 7 independently of one another represent hydrogen or -CC-alkyl
  • radicals R 3 may be the same or different, and are -C 18 alkyl, C 5 -C 6 cycloalkyl, aryl, C 18 -C acyl or arylcarbonyl or together form a C 2 -C 3 alkylene radical can and R 3a is -C 8 -acyl or arylcarbonyl, each aryl group may have one or two substituents which are independently selected from C 1 -C 4 -alkyl, N0 2 and OC ⁇ -C-alkyl,
  • Alkyl means a straight or branched alkyl chain with preferably 1 to 20, in particular 1 to 8 carbon atoms.
  • alkyl are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-hexyl, 2-ethylhexyl, etc.
  • Aryl is preferably phenyl and naphthyl.
  • Alkenyl means a straight or branched alkenyl chain with preferably 2 to 20 carbon atoms.
  • alkenyl examples are vinyl, allyl, 1-butenyl, oleyl, etc.
  • Halogen represents fluorine, chlorine, bromine or iodine, in particular chlorine or bromine.
  • Heterocyclyl stands for a mono- or bicyclic, heterocyclic radical with 3 to 12 ring atoms, which has 1, 2 or 3 heteroatoms, which are independently selected from 0, S and N.
  • the heterocyclic radical can be saturated or unsaturated, be aromatic or non-aromatic.
  • a monocyclic radical with 5 or 6 ring atoms or a bicyclic radical with 10, 11 or 12 ring atoms is preferred.
  • heterocyclic radicals are pyrrolyl, imidazolyl, triazolyl, furyl, oxazolyl, oxadiazolyl, thienyl, thiazolyl, thiadiazolyl, pyridyl, pyrimidyl, indolyl, quinolyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl, tetrahydrochin, tetrahydrocholine
  • the cycloalkyl radical is preferably cyclopentyl or cyclohexyl.
  • the metal cation M preferably represents an alkali metal or the equivalent of an alkaline earth metal cation, in particular sodium, potassium or calcium.
  • the radicals R 2 are preferably C 8 -C 8 -alkyl, polyisobutyl, C 2 -C 2 o-alkenyl (derived from the corresponding unsaturated fatty acids), phenyl, benzyl and allyl. Phenyl and the phenyl radical in the benzyl may be substituted as indicated above. Preferred substituents are -CC 8 alkyl, halogen, N0 2 , CN, C0 2 R 5 and C0 2 M.
  • the radical R 1 of the ⁇ -aminophosphonic acid is preferably identical to the radical R 2 .
  • the triorganyl phosphites of the formula III have at least one acyl group R 3a .
  • R 3a represents C 1 -C 8 -acyl or arylcarbonyl, where each aryl radical can have one or two substituents which are selected independently of one another from C 1 -C 4 -alkyl, N0 2 and OC ⁇ -C 4 -alkyl.
  • R 3a is preferably benzoyl or acetyl.
  • the radicals R 3 can be the same or different and have the same meaning as R 3a or represent -C 8 alkyl, C 5 -C 6 cycloalkyl or aryl, where the aryl radical can have one or two substituents which are independent are selected from one another under C 1 -C 4 alkyl, N0 2 and OC 1 -C 4 alkyl.
  • the R 3 radicals can also together form C 2 -C 3 alkylene.
  • Preferred R 3 radicals are methyl, ethyl and an ethylene group formed by two R 3 radicals.
  • the present invention relates to phosphono compounds of the formula IV, in which the radicals have the meaning given above, and to their preparation in step (a) of the process according to the invention for the preparation of ⁇ -aminophosphonic acids.
  • the radical R a R 2 and R 3 has those given for R 3a . Meanings.
  • the compounds of the formula II are known and can be prepared in a known manner or analogously to known processes.
  • an amine X-CH 2 -NH 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.
  • a formaldehyde source such as aqueous formalin solution or paraformaldehyde
  • the desired hexahydrotriazine can then be obtained by crystallization or evaporation of the water. This process is described in DE-A-2645085, to which reference is hereby made in full.
  • the compound of the formula II, in which X is CN, can be obtained by Strecker synthesis, ie by reacting ammonia, hydrocyanic acid and a formaldehyde source.
  • Strecker synthesis ie by reacting ammonia, hydrocyanic acid and a formaldehyde source.
  • Such a driving is described for example in US 2,823,222, to which reference is hereby made in full.
  • the compounds of the formula III can be prepared by a number of processes.
  • a first possibility is the reaction of a salt of a carboxylic acid R 3 COOH with a phosphorus trihalide, in particular phosphorus trichloride.
  • An alkali metal or alkaline earth metal salt, in particular the sodium, potassium or calcium salt, or the ammonium salt is preferably used as the carboxylic acid salt. This reaction can be carried out without using a solvent and the reaction product obtained can be used directly in step (a).
  • an inert organic solvent in particular in an ether, such as dioxane, tetrahydrofuran etc.
  • 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-tetrachloroethane, chlorobenzene or 1,2-dichlorobenzene, an aliphatic or aromatic hydrocarbon, such as n-octane, toluene, xylene , or nitrobenzene.
  • the same solvent is preferably used as subsequently used in step (a).
  • the use of a chlorinated hydrocarbon is particularly preferred.
  • the salt formed during the reaction for example sodium chloride when using phosphorus trichloride and the sodium salt of the carboxylic acid used, can be discharged after the reaction.
  • ammonium chloride or another ammonium halide is obtained as the salt
  • the ammonia used can be recovered by making an aqueous solution of the salt alkaline (pH 11-14) with a strong base, for example sodium hydroxide solution, and then the ammonia in the customary manner ausstrippt.
  • the ammonia obtained in this way can be recycled after drying, for example by distillation in a liquid or gaseous state, or as an aqueous solution and used to prepare the ammonium salt of the carboxylic acid.
  • Another possibility for the preparation of the compounds of formula III is the reaction of a carboxylic acid R 3 COOH with the phosphorus trihalide in the presence of an amine.
  • the amine used is, in particular, aliphatic or cycloaliphatic di- or triamines, such as triethylamine, tributylamine, dimethylethylamine or dimethylcyclohexylamine, and pyridine.
  • Such a process is generally carried out in an organic solvent. Suitable solvents are given above in connection with the first possibility of production.
  • the amine hydrochlorides are preferably treated with a strong base, for example with aqueous sodium hydroxide solution, the amines are released from the hydrochloride.
  • Volatile amines can then be recovered by distillation or extraction.
  • Non-volatile amines can be recovered by extraction or, if a two-phase mixture is obtained in the amine release, by phase separation.
  • Solid amines can be recovered by filtration. The recovered amines can be returned to the process, if appropriate after drying.
  • Another possibility for the preparation of the compounds of formula III is the reaction of the carboxylic acid R 3 COOH with a phosphorus trihalide, in particular phosphorus trichloride, without the addition of a base.
  • a phosphorus trihalide in particular phosphorus trichloride
  • the released hydrogen halide can then be used in the form of an aqueous solution for the hydrolysis in step (b).
  • Phosphites with one or two acyl groups can be prepared analogously from (R 3 0) 2 PC1 or R 3 0PC1 2 .
  • Step (a) of the process according to the invention can be carried out with or without a solvent, for example in the melt.
  • a solvent for example in the melt.
  • an inert organic solvent for example a hydrocarbon, such as toluene or xylene, an ether, such as tetrahydrofuran, dioxane or dibutyl ether, nitrobenzene, etc.
  • a halogenated solvent in particular a chlorinated, preferably one 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-Te - trachloroethane, chlorobenzene or 1,2-dichlorobenzene.
  • the reaction partners are expediently used in essentially stoichiometric amounts. However, an excess of, for example, up to 10% of one or the other reactant can also be used.
  • the reaction temperature is generally in the range from -10 ° C to 140 ° C, preferably in the range from room temperature to 100 ° C. Under these conditions, only short reaction times are required; in general, the reaction is essentially complete after 10 to 30 minutes.
  • the products obtained in step (a) are processed to give the ⁇ -aminophosphonic acids.
  • the products are subjected to hydrolysis.
  • This can be done acidic or alkaline, preferably hydrolyzed in acid.
  • inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid.
  • the alkaline hydrolysis is generally carried out using an alkali or alkaline earth metal hydroxide, in particular using sodium or potassium hydroxide.
  • the hydrolysis is advantageously carried out with an aqueous acid or base.
  • the aqueous acid or base is generally added to the reaction mixture obtained from step (a).
  • the hydrolysis can be carried out without a solvent or in the presence of a water-miscible, partially miscible or immiscible, inert, organic solvent; the solvent used in step (a) is preferably used.
  • the reaction mixture obtained from step (a) is expediently, if appropriate after removal, e.g. by distilling off part of the solvent.
  • the solvent used in step (a) is completely removed and the residue is subjected to hydrolysis.
  • the solvent recovered from the reaction mixture can be used again in the preparation of the compounds of the formula III or in step (a).
  • the hydrolysis is particularly preferably carried out in a two-phase system (aqueous phase / organic phase).
  • An organic solvent which is partially or immiscible with water is used, preferably a hydrocarbon such as toluene or xylene, an ether such as dibutyl ether and in particular a halogenated hydrocarbon as listed above as solvent for step (a).
  • the hydrolysis is carried out with intensive mixing of the two phases using conventional devices, e.g. Stirred reactors, circulation reactors or preferably static mixers. After the hydrolysis has ended, the phases are separated and worked up as described below.
  • a particularly preferred embodiment is a process in which step (a) is carried out in a halogenated solvent, the solvent is optionally partially removed, and the compound of formula IV obtained is subjected to hydrolysis by reacting the reaction mixture obtained from step (a) with a treated aqueous acid or base.
  • the hydrolysis of the compound of formula IV can also be carried out enzymatically, for example using an esterase or a nitrilase.
  • the acid or base is used in at least equivalent amounts, but preferably in excess, in particular in an amount of> 2 equivalents.
  • the temperature at which the hydrolysis is carried out is generally in the range from about 10 ° C. to 180 ° C., preferably 20 ° C. to 150 ° C.
  • the phosphono compound IV obtained in step (a) can also be extracted into an aqueous phase before the hydrolysis. This has the advantage that the costly partial or complete distillation of the solvent used in step (a) is eliminated. In addition, more stringent hydrolysis conditions can be selected than is possible in the presence of an organic solvent ice, since there is no fear of decomposition of the organic solvent.
  • step (b) of the process according to the invention takes place in the following substeps:
  • step (bl) The reaction product from step (a) is extracted from the reaction mixture of step (a) with water or an aqueous solution of an acid or base, partial saponification possibly already occurring. If desired, it can then be made alkaline by adding a base.
  • step (b3) The compounds contained in the water phase are further reacted, i.e. the not yet hydrolyzed product from step (a) is hydrolyzed.
  • the hydrolysis can be acidic, neutral or alkaline.
  • the pH conditions can correspond to the desired conditions in the subsequent saponification, but it is also possible to extract in a different pH range than that in which the subsequent saponification takes place. For example, you can extract in the acidic or neutral range, then add a base and saponify in the alkaline range.
  • the extraction is preferably carried out at a temperature from room temperature to the reflux temperature of the reaction mixture, particularly preferably at at least 50 ° C.
  • the phase transition of the phosphono compound into the water phase is very fast.
  • extraction times of a few minutes, for example from 5 minutes, are generally sufficient.
  • the extraction time is preferably at least 10 minutes, particularly preferably at least 1 hour. A longer extraction time may be necessary, particularly when extracting at low temperatures, for example at least 2 hours.
  • At least part of the phosphono compound is usually already partially saponified during the extraction. Partial saponification is understood to mean that only a part of the R 3 or R 3a residues contained in the product of stage a) is split off. The extent of saponification depends on the phosphono compound itself and the extraction conditions chosen.
  • the acids used in the extraction are, in particular, inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid.
  • the alkaline extraction is generally carried out using an alkali or alkaline earth metal hydroxide, in particular using sodium or potassium hydroxide.
  • step (a) There is essentially no decomposition of the solvent used in step (a) during the extraction, even if it is a particularly decomposition-sensitive chlorinated hydrocarbon, such as 1,2-dichloroethane.
  • the aqueous phase contains the product of stage a) and optionally its partially saponified product.
  • the phases are separated in a conventional manner known to the person skilled in the art.
  • the product is then hydrolyzed.
  • acid or base can be added to the water phase. Because of the high acid surplus required in acidic saponification, saponification under neutral or alkaline conditions is preferred.
  • the saponification is carried out under elevated pressure in order to achieve the desired reaction temperatures.
  • the reaction temperature in the saponification is preferably higher than in the extraction. In general, the reaction temperature is at least around
  • reaction temperatures are in the range between 100 and 180 ° C, particularly preferably between 130 and 150 ° C.
  • the Reak tion time is preferably between about 5 minutes and 4 hours, more preferably 10 minutes to 2 hours, most preferably about 20 minutes.
  • the acids and bases used for the saponification are generally the acids or bases given above in connection with the extraction.
  • the ⁇ -aminophosphonic acid can then be separated from the aqueous phase (step b4).
  • step (b4) recyclable and / or utilizable constituents are preferably separated off and returned to the process.
  • the ⁇ -aminophosphonic acid obtained in the hydrolysis is now dissolved in the aqueous phase.
  • the carboxylic acid R 3 COOH or R 3a COOH forms directly in the case of hydrolysis with an excess of acid or in the case of base hydrolysis after acidification with a strong acid, preferably to a pH ⁇ 2.0.
  • the carboxylic acid is then separated off in a customary manner, for example by filtering off the carboxylic acid which has precipitated in solid form, distillation or extraction with an organic solvent which is immiscible with the aqueous phase.
  • the carboxylic acid is optionally dissolved in the organic phase.
  • the carboxylic acid is then removed by separating the organic phase and can be recovered from it in the usual manner if desired. It is obtained in high purity and can easily be used again for the preparation of the compound of the formula III.
  • the hydrolysis of the phosphono compounds IV additionally releases alcohols, these are preferably present in solution in the aqueous phase and can be recovered therefrom, for example by distillation. If necessary, they can then be returned to the process.
  • the organic phase bii ⁇ en ⁇ e solvent can be recycled and used again in the preparation of the compound of formula III or in step (a). Before this, however, the solvent is generally subjected to distillation, extraction, filtration and / or stripping in order to remove impurities such as water-soluble or water-insoluble alcohols, phenols, ammonium salts and / or carboxylic acids.
  • the ⁇ -aminophosphonic acid can be adjusted to a pH value which approximates or corresponds to the isoelectric point of the ⁇ -aminophosphonic acid, for example by adding an acid or base, for example HC1, H 2 S0 or NaOH, KOH, Ca (0H ) 2 and optionally precipitated by concentrating the aqueous phase and / or by adding a precipitation aid and obtained in a conventional manner, for example by filtration.
  • the isoelectric points of ⁇ -aminophosphonic acids are generally at pH values in the range from 0.5 to 7.0.
  • a water-miscible solvent such as methanol, ethanol, isopropanol, acetone, etc., is preferably used as the precipitation aid.
  • the solvents can be recovered by distillation from the mother liquor and reused.
  • Ammonia or ammonium chloride formed during the saponification can be returned to the process by making it alkaline, if necessary, and the ammonia being recovered by stripping.
  • the ⁇ -aminophosphonic acid obtained can be decolorized in a conventional manner.
  • This can be done, for example, by treatment with small amounts of a decolorizing agent, for example oxidizing agents, such as perborates or H 2 O 2 , or adsorbents, such as activated carbon.
  • a decolorizing agent for example oxidizing agents, such as perborates or H 2 O 2 , or adsorbents, such as activated carbon.
  • the amount of decolorizing agent depends on the degree of discoloration and can easily be determined by a person skilled in the art.
  • the treatment with the decolorizing agent can be carried out anywhere after the hydrolysis and in the usual way
  • the decolorizing agent is expediently added before the ⁇ -aminophosphonic acid precipitates.
  • the process according to the invention or each stage taken separately can be carried out continuously, discontinuously or as a semi-batch process.
  • Conventional reaction vessels are used for such purposes, such as stirred tanks or tubular reactors, extraction columns, mixer-settlers or phase separators, optionally with upstream mixing devices or mixing elements installed in the tubular reactor.
  • the method according to the invention is thus characterized by simple process control and cheap starting materials. Only an inorganic chloride is obtained as waste and the protective groups, namely the residues of the triorganyl phosphite of the formula III, can be recycled in a simple manner.
  • the process gives ⁇ -aminophosphonic acids in very short reaction times and high yields of> 90%, starting from the hexahydrotriazine of the formula II.
  • 0.2 mol Na benzoate are placed in 50 ml 1,4-dioxane with exclusion of moisture at room temperature. For this, 0.0667 mol of phosphorus trichloride are added dropwise and the mixture is stirred at 85 ° C. for 20 min (colorless suspension). 0.0222 mol of hexahydrotriazine 6 are added and the mixture is stirred for a further 20 min at 85-90 ° C. (thin suspension, easily stirrable). The dioxane is then distilled off in vacuo at 40 ° C. 100 ml of concentrated hydrochloric acid are added to the residue and the mixture is refluxed for 4 h. After cooling, the benzoic acid is filtered off, washed (a little cold water) and dried.
  • the combined filtrates are evaporated to dryness.
  • the phosphonomethylglycine is filtered off and dried.
  • 0.2 mol Na benzoate are placed in 50 ml 1,4-dioxane with exclusion of moisture at room temperature. For this, 0.0667 mol of phosphorus trichloride are added dropwise and the mixture is stirred at 85 ° C. for 20 min (colorless suspension). The mixture is filtered with exclusion of moisture and the residue is washed with a little dioxane. 0.0222 mol of hexahydrotriazine 6 are further added to the filtrate with the exclusion of moisture and the mixture is stirred at 85 ° C. to 90 ° C. for a further 20 minutes. The dioxane is then distilled off in vacuo at 40 ° C. One gives to the backlog 100 ml of concentrated hydrochloric acid and refluxed for 4 h. After cooling, the precipitated benzoic acid is filtered off, washed (a little cold water) and dried.
  • the combined filtrates are evaporated to dryness.
  • the phosphonomethylglycine is filtered off and dried.
  • a solution of 0.12 mol of triacetylphosphite in 50 ml of dioxane is added to a solution of 0.04 mol of hexahydrotriazine 6 in 80 ml of dioxane at room temperature.
  • the solution is stirred at 100 ° C for 2 h.
  • the solvent is then distilled off at 40 ° C. first under normal pressure and later in vacuo.
  • 100 ml of concentrated hydrochloric acid are added to the residue and the mixture is refluxed for 4 h.
  • the reaction mixture is evaporated to dryness.
  • the phosphonomethylglycine is filtered off and dried.
  • the filtrate is placed in a 2 l stirred flask with a teflon blade stirrer and reflux condenser at room temperature and the hexahydrotriazine 6 (45.54 g) is added.
  • the mixture is heated to 80 ° C. in the course of 30 minutes and stirred at 80 ° C. for 30 minutes.
  • the solution is allowed to cool and hydrolyzed immediately afterwards.
  • the feed materials are metered into a tubular reactor (volume approx. 600 ml) with an upstream static mixer at 130 ° C. and 8 bar (1265 g / h of the dichloroethane solution from the previous stage, 207 g / h of 20% HCl).
  • the dwell time is 30 minutes.
  • a preliminary run is discarded.
  • the two-phase mixture obtained is collected for 60 minutes. The phases are separated at 60 ° C and the water phase is extracted twice with 100 g dichloroethane.
  • the dichloroethane still contained in the water phase is first stripped by introducing nitrogen at 60 ° C. for one hour.
  • the resulting suspension is stirred for a further 3 hours at 40 ° C., allowed to cool to room temperature, the precipitated product is filtered off with suction and then washed with 150 g of ice water.
  • the solid obtained is dried at 70 ° C. and 50 mbar for 16 hours.
  • a saturated solution in water is prepared from the ammonium chloride residue from the tribenzoyl phosphite synthesis according to Example 4. This is combined with the mother liquor from the crystallization of the phosphonomethylglycine according to Example 4 and adjusted to pH 14 with excess sodium hydroxide solution. Ammonia is then stripped from the reaction mixture with nitrogen and collected by GC for gas analysis (purity 99%). The combined dichloroethane phases from the saponification are dried by distilling off the azeotrope dichloroethane / water.
  • the combined filtrates are extracted twice with 30 ml of toluene each time, evaporated to dryness and rotated three times with ethanol to remove excess hydrochloric acid.
  • the toluene phase is concentrated and the residue is combined with the recovered benzoic acid.
  • the precipitated phosphonomethylglycine was filtered off, washed with a little water and dried.
  • Example 12 The synthesis was carried out as in Example 12. The temperature was kept at 130 ° C for 10 minutes.
  • Example 12 The synthesis was carried out as in Example 12. The temperature was kept at 130 ° C for 20 minutes.
  • Example 13 The synthesis was carried out as in Example 13.
  • the synthesis was carried out as in Example 18.
  • the reaction mixture was extracted with hexane and the hexane phase was concentrated. The residue was boiled three times with acetonitrile and then filtered until it was free of benzoic acid.
  • Example 25 Synthesis of 2-acetyl-1,3-doxa-2-phospholane as a solution in diethyl ether, via compound 13 with acetyl instead of benzoyl residue
  • Example 26 Synthesis of 2-acetyl-1,3-dioxa-2-phospholane as a solution in dioxane, via compound 13 with acetyl instead of benzoyl residue
  • Example 27 Synthesis of acetoxy-diethoxy-phosphite as a solution in diethyl ether, via compound 12 with acetyl instead of benzoyl residue
  • Example 28 The synthesis was carried out as in Example 28 using a solution of the phosphite in dioxane.

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Abstract

L'invention concerne un procédé pour la production d'acides α-aminophosphoniques, par réaction d'un dérivé d'hexahydrotriazine avec un phosphite de triorganyle. Le procédé selon l'invention comprend comme étape intermédiaire un composé phosphono qui est hydrolysé en acide α-aminophosphonique. L'invention concerne également le composé phosphono lui-même et son procédé de production. Le procédé selon l'invention produit de manière simple et économique des acides α-aminophosphoniques de grande pureté avec un rendement élevé.
EP02780837A 2001-06-22 2002-06-21 Procede pour la production d'acides $g(a)-aminophosphoniques Withdrawn EP1401847A1 (fr)

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DE10130134A DE10130134A1 (de) 2001-06-22 2001-06-22 Verfahren zur Herstellung von alpha-Aminophosphonsäuren
DE10130134 2001-06-22
PCT/EP2002/006901 WO2003000702A1 (fr) 2001-06-22 2002-06-21 Procede pour la production d'acides $g(a)-aminophosphoniques

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US4053505A (en) * 1976-01-05 1977-10-11 Monsanto Company Preparation of n-phosphonomethyl glycine
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AR035252A1 (es) 2004-05-05
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WO2003000702A1 (fr) 2003-01-03
US20040236144A1 (en) 2004-11-25

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