MXPA00001773A - Method for producing glufosinates and intermediate products for the same - Google Patents

Abstract

According to the invention, glufosinates and their 2-methyl analogues are produced in a multi-stage synthesis from methyl phosphor compounds (II) with unsaturated keto compounds (III) via adducts (IV), subsequent reaction in Strecker synthesis conditions and finally, hydrolysis of the aminonitrile (V):Stage 1:(II) + (III)?Adduct (IV);stage 2:Adduct (IV) for example NH3/NaCN/NH4Cl (V);stage 3:Hydrolysis of (V) to glufosinates. Various compounds are identifiable as adducts (IV), depending on the method conditions and substrates.

Description

* Í3 PROCEDURE FOR PREPARING ELL-PHOSINATE AND INTERMEDIATE COMPOUNDS FOR THE SAME DESCRIPTIVE MEMORY The invention relates to the technical field of the processes for preparing biologically active compounds and precursors thereof, preferably of seed protection agents, in particular glufosinate herbicide, also known as phosphinothricin. Glufosinate (see formula (la)) is the common name for the active compound (D, L) -2-amino-4- [hydroxy (methyl) phosphinyl] butanoic which is commercially available as the monoammonium salt and is used as foliar herbicide (see DE-A-2717440, US-A-4168963).

The herbicide can be used for the non-selective control of weeds in a fruit and viticulture crop, in tree plantings, in a vegetable crop before planting or transplanting, before directing the planting of corn or soybeans, and also on uncultivated land, such as roadsides, industrial land and railways (see Z. PflKrankh, PflSchutz, special edition IX, 431-440, 1981). The selective use for controlling weeds in plantings of useful plants, such as, among others, corn and rapeseed, which have been made resistant by gene technology is also known (see EP-A-0242246). A large number of methods have been provided for preparing glufosinate. According to the variant described in EP-A-0011245 (US-A-4521348), the phosphorus-containing cyanohydrin derivatives of the formula wherein R is a hydrocarbon radical, such as alkyl, haloalkyl, cycloalkyl, phenyl or benzyl, with or without substitution, R 'is hydrogen, alkyl, phenyl or benzyl and R "is hydrogen, acyl, trialkylsilyl or alkylsulfonylalkyl, can be converting to aminonitriles, which at the same time can be hydrolyzed to glufosinate.According to EP-A-0011245, the preparation of the cyanohydrin derivatives is carried out by the reaction of a monoalkyl methanphosphonate and an acrolein-cyanohydrin derivative of the formula in which R 'and R "are as defined above The method described has the disadvantage that the phosphorus-containing derivative and its precursors must be provided in the form of esters, while in the desired product glufosinate (la), the (hydroxy) (methyl) phosphinyl radical in hydrolyzed form is present. It is an object of the present invention to provide an alternative process to the process described above, allowing said process to produce the number of ester precursors and being suitable for preparing glufosinate and related compounds. The invention provides a process for preparing compounds of the formula (I), wherein R is hydrogen or C-? -C alkyl, preferably H or methyl, or salts thereof with acids or bases, which comprises a) (Step 1) reacting a trivalent methylphosphorus compound of the formula II) with an unsaturated derivative of the formula (III), if appropriate in the presence of a condensing or activating agent and, if appropriate, alcohols, to give an adduct (IV), Step 1 : H3C-P - »- Adduct IV (II) (III) (IV) wherein in the formulas R1 and R2 are independently from each other halogen, such as, for example, fluorine, chlorine, bromine or iodine, CC ?8 alkoxy with or without substitution, benzyloxy or phenoxy, which may also be substituted, or one of the radicals R1 and R2 is hydroxyl, and R * is as defined in formula (I); b) (Step 2) the adduct (IV) is reacted, if appropriate after the opening of the hydrolytic ring to aldehydes (R * = H) or ketones (R * = alkyl) of the formula (IV) or salt of the same, (IV ') in which Z is OH, R1 or R2, under the conditions of a Strecker synthesis with ammonia / ammonium chloride and sodium cyanide or alternatively with mixtures of ammonia and hydrocyanic acid or with ammonia or an acid salt hydrocyanic, such as, for example, ammonium cyanide or potassium cyanide, if appropriate in the presence of ammonium chloride, to give the a-aminonitriles of the formula (V) or a salt thereof, Step 2: Adduct IV v.gr. NH3 / NaCN / NH4CI (V) wherein in the formulas (IV) and (V) the radical R * is as defined in the formula (I) and Z is as defined in the formula (IV) or is OH; and c) (Step 3) the compound of the formula (V) is hydrolyzed under acidic or basic conditions to give the compound of the formula (I) or the salt thereof. In the formulas mentioned above and the formulas used hereinafter, the alkyl, alkoxy, haloalkyl, haloalkoxy, alkylamino and alkylthio radicals, and also the corresponding unsaturated radicals and / or radicals which are substituted in the carbon structure, can be each case of straight or branched chain. Unless specifically indicated, preference is given by these radicals to the lower carbon structures, for example those having 1 to 4 carbon atoms and, in the case of the unsaturated groups, those having 2 to 4 carbon atoms. Alkyl radicals, also in the compound meanings such as alkoxy, haloalkoxy, etc. they are, for example, methyl, ethyl, n- or i-propyl, n-, i-, t- or 2-butyl, pentyls, hexyl, such as n-hexyl, i-hexyl and 1,3-dimethylbutyl, heptyls , such as n-heptyl, 1-methylhexyl 1,4-dimethylpentyl; the cycloalkyl is a carbocyclic saturated ring system, having, for example, from 3 to 8 ring atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc .; the alkenyl, alkynyl and cycloalkenyl radicals have the meaning of the possible unsaturated radicals corresponding to the alkyl or cycloalkyl radicals; alkenyl is, for example, allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1- ilo, methylbut-3-en-1-yl and 1-methylbut-2-en-1-yl; cycloalkenyl is, for example, cyclopentenyl or cyclohexenyl; Alkynyl is, for example, propargyl, but-2-yn-1-yl, but-3-yn-1-yl or 1-methylbut-3-yn-1-yl. Alkenyl in the form of "C3-C4 alkenyl" or "C3-C6 alkenyl" is preferably an alkenyl radical having from 3 to 4 and from 3 to 6 carbon atoms, respectively, wherein the double bond is not adjacent to the carbon atom that is attached to the remainder of the molecule portion of the compound (I) ("ilo" position). Alquinílo of C3-C, etc. Halogen is, for example, fluorine, chlorine, bromine or iodine. Halogenoalkyl, -alkenyl and -alkynyl are alkyl, alkenyl and alkynyl, respectively, which are partially or completely substituted by halogen, preferably by fluorine, chlorine and / or bromine, in particular by fluorine or chlorine, for example CF3, CHF2, CH2F, CF3CF2 > CH2FCHCI2 > CCI3, CHCI2, CH2CH2CI; halogenoalkoxy is, for example, OCF3, OCHF2, OCH2F, CF3CF2O, OCH2CF3 and OCH2CH2CI; this applies correspondingly to halogenoalkenyl and to other radicals substituted with halogen.

. »-Ba > * «.arfe, ..

If the substitutions are defined by "one or more radicals selected from a group of radicals", these include both substitution by one or more identical radicals such as mono- or polysubstitution of different radicals. Substituted radicals, such as substituted hydrocarbon radicals, for example, alkenyl, alkynyl, aryl, phenyl and substituted benzyl, or substituted heterocyclyl, are, for example, a substituted radical derived from the original unsubstituted radical, wherein the substituents are, for example, example, one or more, preferably 1, 2 or 3, radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro, cyano, azido, alkoxycarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, amino substituted such as acylamino, mono- or dialkylamino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl and, in the case of the cyclic radicals, also alkyl and haloalkyl, the radical is unsaturated aliphatics corresponding to the unsaturated hydrocarbon-containing radicals mentioned above, such as alkenyl, alkynyl, alkenyloxy, alkynyl, etc. Preferred radicals having carbon atoms are those having 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms. Preferred substituents are usually from the group consisting of halogen, for example fluorine or chlorine, CrC4 alkyl, preferably methyl or ethyl, haloalkyl of C -? - C, preferably trifluoromethyl, C1-C4 alkoxy, preferably methoxy or ethoxy, haloalkoxy of C1-C4, nitro and cyano. Particular preference is given to the methyl, methoxy and chloro substituents. The phenyl with or without substitution is preferably phenyl which is unsubstituted or mono- or polysubstituted, preferably up to trisubstituted, by different identical radicals selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, haloalkyl CrC4 , halogenalkoxy of C? -C4, and nitro, for example o-, m- and p-tolyl, dimethylphenyls, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4-trifluoro- and trichlorophenyl, 2, 4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m- and p-methoxyphenyl. An acyl radical is the radical of an organic acid, for example the radical of a carboxylic acid and acid radicals derived therefrom, such as tricarboxylic acid, iminocarboxylic acids with or without N-substitution, or the monoester radical of carbonic acid , carbaminic acids with or without N-substitution, sulfonic acids, sulfinic acids, phosphonic acids, phosphinic acids. The acyl is, for example, formyl, alkylcarbonyl such as (C 4 -C alkyl) carbonyl, phenylcarbonyl, wherein the phenyl ring can be substituted, for example as shown above by phenyl, or alkyloxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, alkylsulfonyl, alkylsulfinyl, N-alkyl-1-iminoalkyl and other organic acid radicals. Compounds of the formula (II) are known or can be prepared by known procedures; see, for example, J.B. Miles et al. in Org. Prep. Proc. Int., H (1), 11 (1979); B.M. Gladshtein et al., Zh. Obshch. Kim. 39, 1951 (1969); DAS 1098940 (1959), Farbt Bayer, Boetzel et al., J. Fluorine Chem. 68, 11 (1994); Hoffmann et al., JACS 80, 1150 (1958). In the compounds of the formula (II), R1 and R2 are independently of each other preferably halogen, such as, for example, fluorine, chlorine, bromide or iodine, CrC6 alkoxy, CrCβ halogenoalkoxy, benzyloxy or phenoxy, wherein each of the two radicals mentioned to the latter is unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkylthio, nitro, cyano, alkylsulfonyl and haloalkylsulfonyl, preferably having each The case of 1 to 6 carbon atoms, in particular of 1 to 4 carbon atoms, in the alkyl portion, or one of the radicals R1 and R2 is preferably hydroxyl. Particularly preferably, each of R1 and R2 is C? -C4 alkoxy. The compounds of the formula (III) are basic chemical substances and therefore also known. The adducts (IV) can have several structures. Intermediates which are possible in some cases are the 2-methyl-1,2-oxa-4-phospholenes of the formula (IV *), ie the subsequent reactions are compatible with an intermediate compound of the formula (IV *): ».-« *? * "* J In certain cases, the compounds of the formula (IV *) are present as intermediates which can not be detected or are not present at all, depending on which activators or condensing agents reactive additives, such as alcohols, they are used in the condensation / addition reaction. In a preferred embodiment, preference is given to reacting the compounds of the formula (11-1) with a compound of the formula (III) in the presence of A2O anhydrides, preferably carboxylic anhydrides, and alcohols ROH, to give the adducts (IV -1), being the last semiacetals with a salt of them, (IH) (III) (IV-1) wherein -OX and OY correspond to the radials R1 and R2, respectively, if these are radicals of alcohols, ie each of the radicals X and Y is independently of each other H or C-pC-is alkyl which is benzyl or unsubstituted or substituted phenyl, wherein each of the two radicals mentioned above is unsubstituted or substituted, preferably unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkylthio, nitro, cyano, alkylsulfonyl and haloalkylsulfonyl, preferably having in each case from 1 to 6 carbon atoms, in particular from 1 to 4 carbon atoms in the alkyl portion and X and Y are preferably identical radicals and in particular X, Y and R are identical radicals, R * is as defined in formula (I), preferably H, A is an acyl radical, preferably the acyl radical of a carboxylic acid having from 1 to 6 carbon atoms, in particular 1 to 4 carbon atoms. R is a radical selected from the group of radicals defined for X and Y, preferably from the same radical as X or Y. Particularly preferably, X, Y and R are identical radicals selected from the group consisting of C-alkyl. Cβ, phenyl benzyl, in particular C 1 -C alkyl, for example methyl, ethyl, n-propyl, n-, i-, s- or t-butyl. Correspondingly, the compounds (IV) and (V) are, in the preferred variant (starting from the compounds (IV-1)) compounds of the formula (V-1), respectively, wherein X '= H or X and R * and X or salts thereof. The 2-methyl-1,2-oxa-4-phospholenes of the formula (IV *) and the semiacetals of the formula (IV-1) have hitherto been unknown as have the aminonitriles of the formula (V-2) ) (formula (V) where Z = OH).

(V-2) and therefore form part of the subject matter of the present invention. Of the 1,2-oxa-4-phospholenes (IV *), only some higher homologs are known. Thus, phenyldichlorophosphane (lia) reacts with α, β-unsaturated acetonas (VI) by the addition of acetic anhydride to give the 2-phenyl-2-oxo-1,2-oxa-4-phospholenes (VII) (K. Bergesen, Acta Chem. Scand., 19, 1784 (1985)), - s - "'- (» a) (VI) VII) in which R3 and R4 are hydrogen, methyl or phenyl and R5 is methyl or phenyl In addition, it is known that ethyldichlorophosphane (IIb) reacts with methyl vinyl ketone (Via) ) to give 5-methyl-2-ethyl-2-oxo-1,2-oxa-4-phospholene (Vlla) (AN Pudovik et al., Isv. Akad. Nauk. SSSR, Ser. Khim. (English version) ) 2543 (1970)), Et = ethyl in the formula (lb), Me = methyl in the formula Vlla; Ac = acetyl; (llb) (Via) (Vlla) Finally, the reaction of 2-thienyldichlorophosphane (He) with α, β-unsaturated ketones gives 2-thienyl-2-oxo-1,2-oxa-4-phospholenes (Vllb) (Rzaliev, Isv. Akad. Nauk., SSSR, Ser. Khim (English version), 2719 (1973)), íg ^ '* J & r? á ^^ (He) (Vlc) (Vllc) wherein R6 is hydrogen or methyl. No analogous reactions have now been described in the literature, for example with methyldichlorophosphane which is highly reactive compared to phenyldichlorophosphane (see H. Heydt et al, Methoden der Organischen Chemie XII E2, p.29 (1982)) and methane phosphonous acid diesters . Analogous reactions with acrolein (II, R2 = H) are not known either. Since the components (II) and (III) are much more reactive and due to the effect of the complex reactive mixture or the complex cost of the reaction in step 1, it is extremely surprising that the process according to the invention can be carried out with high yields through the intermediates (adducts IV) to give the a-aminonitrile (V) or (V-1) derivatives and subsequently the compounds (I). In step 1, the process according to the invention is generally carried out by reacting the compounds of the formula (II) or (11-1) with unsaturated compounds of the formula (III), preferably in the presence of a condensing agent or activator. Suitable activators / condensing agents are substances that are suitable to promote or catalyze the adhesion of the phosphorus component to the compound fcj 2J ^ t ^ - £ ¿$ s - * & - 'a, ß-unsaturated (III). Suitable condensation agents or activators are carboxylic anhydrides, preferably anhydrides of alcacarboxylic acids having from 1 to 6 carbon atoms, for example acetic anhydride or propionic anhydride. Mixtures of the anhydrides with certain proportions of alcohols of ROH are also suitable, where R is as defined above. The reaction of the compounds (II) and (III) can be carried out without solvent or in the presence of an organic solvent, for example in the presence of aliphatic or aromatic hydrocarbons which can be halogenated, such as dichloromethane, toluene, xylene, chlorobenzene , or ethers, such as dioxane, or alcohols, such as ethanol, n-butanol, etc., or mixtures of these exemplary solvents. The phosphorus components of the formula (II) are used in molar ratios that can deviate considerably from the stoichiometry, preferably in molar ratios of 1: 2 to 2: 1, but in particular essentially in equimolar amounts, based on the component (lll) If the reaction of components (II) and (III) is carried out in the presence of an A2O anhydride, such as, for example, acetic anhydride or propionic anhydride, suitable anhydride entries are usually in the range of more than 0. to 400% by mol, preferably amounts of 50 to 150% by mol, based on the starting component (II) or (III), which is employed in the lowest molar amount. If the reaction of the components (11-1) and (III) presence of the A2O anhydride, for example acetic anhydride, and an alcohol ROH for example (C1-C5) alkanol such as ethanol is carried out, preference is given to use of 50 to 150% in mol of acetic anhydride and 50 to 200% of alcohol, in particular in the anhydride: alcohol ratio from 1: 1 to 1: 1.5, based on the starting component (II) or (III) ), which is used in the lowest molar quantity. The reaction, according to the invention, of the compounds (II) and (III) is generally well at a reaction temperature between -80 ° C and + 200 ° C, preferably between -10 ° C and + 60 ° C. The duration of the reaction depends on the reaction temperature, the batch size, the specific reagents, the solvent and the condensing agents / activators and is, for example, in the range 0.5-48 hours (h) preferably 0.5- 18 h. Surprisingly, the reaction, according to the invention, of the intermediate compounds (IV) and (IV-1) can be carried out to give the desired a-aminonitriles (V) and (V-1), respectively (step 2) ), under conditions that are known analogously to the preparation of aminonitriles from aldehydes or ketone by the type of "Strecker Synthesis" (see textbooks and organic chemical synthesis manuals). According to a possible procedure, the reaction solution containing the crude product (IV) or (IV-1) is added to a solution or suspension containing an alkali metal safe and an ammonium chloride in aqueous ammonia solution. It is also possible to use mixtures of the aforementioned organic solvents, such as toluene, xylene, chlorobenzene, dichloromethane, ethanol, butanol, etc., for this purpose. Instead of alkali metal cyanides, it is also possible to use alkaline earth metal cyanides or an ammonium cyanide, or solutions of cyanhydric acid in ammonia. The cyanides of cyanhydric acid are used, for example, in amounts of 80-130 mol%, but preferably in essentially equimolar quantities, based on the components of the formula (IV). The amount of ammonia based on the compound (IV) is, for example, between 100 and 80% mol, preferably 100 to 400 mol%. The reactions of the compounds (IV) are carried out under the conditions of the Strecker syntheses, for example at -10 ° C and up to 100 ° C, preferably at 0-45 ° C. The compounds of the formula (V) or (V-1) are preferably obtained as salts in which the acid hydrogen atom in the phosphinoyl group is replaced by a cation equivalent, preferably by a cation equivalent such as, for example, , Li + Na +, K +, (Mg2 +) 1/2, (Ca2 +)? / 2, NH4 +. Alternatively, it is possible to initially purify intermediates (IV) or (IV-1) by distillation and extractive methods and reacting in purified form to give the aminonitriles (V) or (V-1).

In a further variant, the intermediates (adults (IV) (IV-1)) are initially hydrolyzed with water to give the aldehydes and acetones of the formula (IV) or (IV-1) and are reacted in a step further to give the a-aminonitriles (V) or (V-1). In the formula (IV), R * is hydrogen or C1-C4 alkyl. The compounds in which R * = hydrogen and Z = hydroxyl or salts thereof are novel compounds in the methylphosphinic acid series and therefore also form part of the subject matter of the invention, ie the compound of the formula (IV- 2) or salts thereof.

However, compound (IV) is known wherein R * = methyl and Z = hydroxyl L.D. Quin et al. J. Org. Chem. 39, 686 (1974)). According to step 3 of the process according to the invention, the a-aminonitriles of the formula (V) or (V-1) are useful intermediates in which, in analogy with the process conditions known from the literature ( Houben-Wyl, Methoden der Organischen Chemie XI / 2, p.305, and p.371, 1958), can be hydrolysed in both acidic and basic media, to give the biologically active amino acids of the formula (I), in particular glufosinate of the formula (la). Compared with the known processes for the synthesis of the herbicidal amino acid (la), the process according to the invention has a number of advantages, for example, the additional esterification of the phosphorus components of the intermediates (IV), (IV) and (V) of the intermediate compounds in unnecessary. In addition, the process can optionally be carried out separately for each step or as a vessel procedure in all 3 steps. Thus, the essential PC bond can be carried out to form the amino acid side chain, for example with methyldialogenophosphanes or, preferably, diesters of methanophosphonous acid (II) or (11-1) and olefins (III), without being necessary the complicated conversion of, for example, methyldichlorophosphate to monoesters of methane-phosphonous acid. Furthermore, in contrast to the process known from EP-A-0011245, the radial addition of the monoesters of methanophosphonous acid derived from acrolein is emitted, according to and easily to their products. In the process according to the invention it is possible to use, for example, easily obtained olefin components, acrolein or methyl vinyl ketone directly, without the transformation of derivatives being necessary. In addition, the a-aminonitriles (V) or (V-1) the process according to the invention is obtained by a group of free phosphenic acid or phosphinate, so that in the last step of the synthesis only the group is hydrolyzed. nitrile to give the free amino acid. In the blockage of the group phosphonic acid, which is required in the prior art mentioned above, is phosphonic, thus it is superfluous.

The examples below illustrate the procedure, without limiting the possible procedural conditions. Not only is it specifically defined differently the established amounts are based on weight.

EXAMPLE 1 2-Amino-2-methyl-4- (hydroxymethylphosphinyl) butyric acid 1 ammonium salt At room temperature and under an inert gas atmosphere, 7.01 g (0.10 mol) of methyl vinyl ketone is mixed with 10.21 g (0.10 mol) of acetic anhydride. Upon cooling to a high 25-30 ° C, another drop 13.61g (0.10 mol) of diethyl metanephosphonate is subsequently added.

The reaction mixture is filtered at 30 ° C for about 6 hours. TO -25 ° C, the mixture or a solution 4.41 g (0.09 mol) d4e sodium cyanide and 9.63 g (0.18 mol) of ammonium chloride in 50 ml of ammonia solution (25% strength) is added dropwise. The mixture is stirred at 25 ° C for a further 4 hours and another drop is quickly added again without isolation of the crude aminonitrile to 200 ml of hydrochloric acid (concentration at 37%). The effective mixture is subsequently boiled under reflux for about 4 hours, while distilling off in ethanol and acetic acid. The mixture is concentrated using a rotary evaporator, a pH of about 9 is adjusted using ammonia solution and salts are released into the desired product by recrystallization from methanol.

This gives 19.1 g (corresponding to 94.5% of theory) of 2-amino-2-methyl-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt. 1 H NMR (D2O): 1.56 (d, J = MHz, 3H); 1.63 (s, 3H); 1.7-2.3 (m, 4H) 31P NMR (D2O): 54.4.

EXAMPLE 2 2-Amino-2-methyl-4- (hydroxymethylphosphonyl) butyric acid, ammonium salt At room temperature, 2.10 g (0.03 mol) of methylvinyl ketone 3.06 g (0.03 mol) of acetic anhydride are dissolved in 20 ml of dichloromethane. At 25-28 ° C, 3.51 g (0.03 mol) of methyldichlorophosphine is added dropwise rapidly and stirred in the mixture at about 30 ° C for 3 hours and then added dropwise to a solution of 1375 g ( 0.0275 mol) of sodium cyanide and 2.94 g (0.055 mol) of ammonium chloride in 25 ml of ammonia (concentration at 25%). The mixture is stirred at 28-30 ° C for about 4 hours and the two-phase crude aminonitrile solution at 25-30 ° C is added dropwise to 100 ml of hydrochloric acid (concentration at 37%). The mixture is subsequently heated under reflux for about 4 hours and worked up as in Example 1. This gives 5.83 g (corresponding 92% of theory) of 2-amino-2-methyl-4- (hydroxymethylphosphonyl) butyric acid, salt of ammonium. 1 H NMR (D2O): 1 57 (d, J = MHz, 3H); 1.65 (s, 3H); 1.7-2.3 (m, 4H) 31P NMR (D2O): 54.5.

EXAMPLE 3 2-Amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt At room temperature, 5.61 g (0.10 mol) of freshly distilled acrolein are added to 10.21 g (0.10 mol) of acetic anhydride. At 25-30 ° C, 13.61 g (0.10 mol) of diethyl methanphosphonate is subsequently added dropwise. The mixture is stirred at 30 ° C for two hours and then at 25-28 ° C, added dropwise to a solution of 4.9 g (0.10 mol) of sodium cyanide and 10.7 g (0.20 mol) of ammonium chloride. in 50 ml of ammonia (25% concentration). After two hours at 30 ° C, the crude aminonitrile is added dropwise to 200 ml of hydrochloric acid (concentration 37%). The mixture is subsequently heated under reflux for two hours, while distilling off ethanol and acetic acid. The mixture is concentrated using a rotary evaporator, a pH of about 9 is adjusted using ammonia solution and the product is purified by crystallization from methanol. This gives 19.4 g (98% of theory) of 2-amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt. 1 HNMR (D2O): 1.60 (d, 14Hz, 3H); 1.8-2.4 (m, 4H); 4.28 (t, J = 6 Hz, 1 H) 31P NMR (D2O): 55.9.

EXAMPLE 2-Amino-2-methyl-4- (hrdroxymethylphosphunyl) butyric acid, ammonium salt At room temperature and under an inert gas atmosphere, 14.02 g (0.20 mol) of methyl vinyl ketone are mixed with 20.42 g (0.20 mol) of acetic anhydride. With cooling at most 25-30 ° C, a mixture of 27.22 g (0.20 mol) of diethyl metanephosphonate and 9.2 g (0.2 mol). The reaction mixture is filtered at 30 ° C for about 6 hours. At 20-25 ° C, the mixture or a solution 8.82 g (0.18 mol) of sodium cyanide and 19 26 g (0.36 mol) of ammonium chloride in 100 ml of ammonia solution (concentration 25%) is added dropwise. ). The mixture is stirred at 25 ° C for a further 4 hours and another drop is quickly added again without isolation of the crude aminonitrile to 400 ml of hydrochloric acid (concentration at 37%). The effective mixture is subsequently boiled under reflux for about 4 hours, while distilling off in ethanol and acetic acid. The mixture is concentrated using a rotary evaporator, a pH of about 9 is adjusted using ammonia solution and salts are released into the desired product by recrystallization from methanol. This gives 38.8 g (corresponding to 96% of the theory) of 2-amino-2-methyl-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt for physical data, see example 1).

EXAMPLE 5 2-Amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt At room temperature, 5.61 g (0.10 mol) of freshly distilled acrolein are added to 10.21 g (0.10 mol) of acetic anhydride. At 25-30 ° C, this mixture is subsequently added dropwise to 13.61 g (0.10 mol) of diethyl methanphosphonate and 4 6 g (0 1 mol) of ethanol. The mixture is stirred at 30 ° C for two hours and then at 25-28 ° C, added dropwise to a solution of 4.9 g (0.10 mol) of sodium cyanide and 10.7 g (0.20 mol) of ammonium chloride. in 50 ml of ammonia (25% concentration). After two hours at 30 ° C, the crude aminonitrile is added dropwise to 200 ml of hydrochloric acid (concentration 37%). The mixture is subsequently heated under reflux for two hours, while distilling off ethanol and acetic acid. The mixture is concentrated using a rotary evaporator, a pH of about 9 is adjusted using ammonia solution and the product is purified by crystallization from methanol. This gives 19.6 g (99% of theory) of 2-amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt. 1HRMN (D2O): 1 60 (d, 14Hz, 3H); 1.8-2.4 (m, 4H); 4.28 (t, J = 6 Hz, 1 H) 31P NMR (D2O): 55.9.

EXAMPLE 6 2-Amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt At room temperature, 5.61 g (0.10 mol) of 5 freshly distilled acrolein are added to 10.21 g (0.10 mol) of acetic anhydride. At 25-30 ° C, this mixture is subsequently added dropwise to 16.41 g (0.10 mol) of diethyl methanphosphonate and 14.8 g (0.2 mol) of n-butanol. The mixture is stirred at 30 ° C for two hours and then at 25-28 ° C, added dropwise to a solution of 4.9 g (0.10 mol) of sodium cyanide and 10.7 g (0.20 mol) of Ammonium chloride in 50 ml of ammonia (25% concentration) After two hours at 30 ° C, the crude aminonitol is added dropwise to 200 ml of hydrochloric acid (concentration 37%). The mixture is subsequently heated under reflux during two hours, while distilling out ethanol and acetic acid. The mixture is concentrated using an evaporator After rotating, a pH of about 9 is adjusted using ammonia solution and the product is purified by methanol crystallization. This gives 17.8 g (90% of theory) of 2-amino-4- (hydroxymethylphosphinyl) butyric acid, ammonium salt. 1HRMN (D2O). 1.60 (d, 14Hz, 3H); 1.8-2.4 (m, 4H); 4.28 (t, J = 6 Hz, 1 H) 31 P NMR (D 2 O): 55.9. siés m is &ákM m-aa *

Claims (14)

NOVELTY OF THE INVENTION CLAIMS

1. - A process for preparing compounds of the formula (I), wherein R is hydrogen or CC alkyl or salts thereof with acids or bases, which comprises: a) (Step 1) reacting a trivalent methylphosphorus compound of the formula (II) with an unsaturated derivative of the formula (III), in the presence of a condensing or activating agent and, if appropriate, alcohols, to give an adduct (IV), Step 1: Adduct IV (II) (III) (IV) wherein in the formulas R1 and R2 are independently from each other halogen, such as, for example, fluorine, chlorine, bromine or iodine, C-? -C-? 8 alkoxy with or without substitution, benzyloxy or phenoxy, which they may also be substituted, or one of the radicals R1 and R2 is hydroxyl, and R * is as defined in formula (I); b) (Step 2) the adduct (IV) is reacted, if appropriate after hydrolysis to aldehydes (R * = H) or ketones (R * = alkyl) of the formula (IV) or salt thereof, (IV) in which Z is OH, R1 or R2, under the conditions of a Strecker synthesis with ammonia / ammonium chloride and sodium cyanide or alternatively with mixtures of ammonia and hydrocyanic acid or with ammonia or a hydrocyanic acid salt , if appropriate in the presence of ammonium chloride, to give the a-aminonitriles of the formula (V) or a salt thereof, Step 2: Adduct IV v.gr. NH3 / NaCN / NH4CI (V) wherein in the formulas (IV) and (V) the radical R * is as defined in the formula (I) and Z is as defined in the formula (IV) or is OH; and c) (Step 3) the compound of the formula (V) is hydrolyzed under acidic or basic conditions to give the compound of the formula (I) or the salt thereof.

2. The process according to claim 1, further characterized in that R1 and R2 are independently of each other Ci-Cß alkoxy, Ci-Cβ halogenoalkoxy, benzyloxy or phenoxy, wherein each of the two radicals mentioned last is unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, alkyl, haloalkyl, alkylthio, nitro, cyano, alkylsulfonyl and haloalkylsulfonyl, each having 1 to 6 carbon atoms in the alkyl portion, or one of the radicals R1 and R2 is preferably hydroxyl.

3. The process according to claim 1 or 2, further characterized in that in step 1, as compounds (II), the compounds of the formula (11-1) are reacted with a compound of the formula (III) in the presence of anhydrides A2O and alcohols ROH to give the adducts (IV) 10 of the formula (IV-1), 15 (11-1) (III) (IV-1) in which each of the radicals X and Y is independently of each other H or (C C-is) alkyl which is unsubstituted or substituted benzyl or phenyl, wherein each of the two radicals mentioned above is unsubstituted or substituted; and A is a radical acyl; R is alkyl of (C C-is), which is benzyl or unsubstituted or substituted phenyl, wherein each of the two above radicals is unsubstituted or substituted.

4. The process according to claim 3, further characterized in that each of X, Y and R is (C1-C4) alkyl; A is an acyl radical of an alkancarboxylic acid having from 1 to 6 carbon atoms; and R * is a hydrogen atom.

5. A process for preparing compounds of the formula (I), wherein R * is hydrogen (C1-C4) alkyl or salts thereof with acids and bases, which comprises hydrolyzing a compound of the formula (V-2) or salts thereof, (V) in which R * is as defined in formula (I) under acidic or basic conditions to give the compound of formula (I) or salts thereof.

6. The process according to claim 5, further characterized in that the compound of the formula (V-2) or a salt thereof is prepared from compounds of the formula (IV *), (IV *) wherein R * is as defined in formula (V), if appropriate after opening of hydrolytic ring aldehydes or ketones of formula (IV), in which Z = OH and R * is as defined in formula (V-2), by reaction and conditions of a Strecker synthesis with ammonia / ammonium chloride and sodium cyanide or relatively with mixtures of ammonia and acid hydrocyanidride or with ammonia and a hydrocyanic acid salt, if appropriate in the presence of ammonium chloride, to give an a-aminonitriles of the formula (V-2) or a salt thereof.

7. A process for preparing compounds of the formula (V) or salts thereof (V) in which Z and R * are as defined in step 2 of claim 1, which comprises reacting compounds of the formula (IV-1), (IV-1) in which X, A and R are as defined in 3 and R * is as defined in formula (V), if appropriate after hydrolysis to aldehydes or ketones of the formula (IV) wherein Z = OH or OX, X is as defined in formula (IV-1) and R * is as defined in formula (V), under the conditions of Strecker synthesis with ammonia / ammonium chloride and Sodium cyanide or alternatively mixtures of hydrocyanic ammonia or with ammonia and a hydrocyanic acid salt, if appropriate in the presence of ammonium chloride, to give α-aminonitriles of the formula (V) or a salt.

8.- A compound of the formula (V-2) or salts thereof with acids and bases, (V-2) wherein R * is H or (C1-C4) alkyl.

9. A compound of the formula (IV *), (IV) wherein R * is hydrogen or (C1-C4) alkyl.

10. The process for preparing compounds of the formula (IV *) according to claim 9, further characterized in that a trivalent methyl phosphorus compound of the formula (II) is reacted with an unsaturated derivative of the formula (III) ) in the presence of an agent of 10 condensation or activator to give a 1,2-oxa-4-phospholene of the formula (IV *), (ll) (III) (IV *) 15 wherein in formulas (II) and (III) R1 and R2 are as defined in claim 1 and R * is as defined in formula (IV *).

11. A compound of the formula (IV-1), (IV-1) It is in which X, A and R are as defined in claim 3 and R * is H or alkyl of (C1-C4) or salts thereof.

12. The process for preparing compounds of the formula (IV-1) or salts thereof according to claim 11, further characterized in that the compounds of the formula (11-1) are reacted with a compound of the formula (III) in the presence of A2O anhydrides and ROH alcohols to give the adducts of the formula (IV-1) or salts thereof. (in) (III) (IV-1) wherein each of the radicals X and Y is independently of each other H or alkyl of (C-I-C-IS) which is benzyl or unsubstituted or substituted phenyl, wherein each of the two radicals mentioned above is unsubstituted or substituted; And it's a radical acyl; R is alkyl of (C-pC-is), which is benzyl or unsubstituted or substituted phenyl, wherein each of the two above radicals is unsubstituted or substituted.

13. The process according to claim 12, further characterized in that from 50 to 150% by mol of A2O anhydride and from 50 to 200% by mol of alcohol ROH, with base of starting component (11-1) or (lll) that has the lowest molarity.

14. - A process for preparing compounds of the formula (I), wherein R * is hydrogen or (C1-C4) alkyl or salts thereof with acids or bases which comprises reacting compounds of the formula (IV-1), (IV-1) in which R * is as defined in formula (I); each of the radicals X and Y is independently of each other H or alkyl of (C-I-C-IS) which is benzyl or unsubstituted or substituted phenyl, wherein each of the two radicals mentioned above is unsubstituted or substituted; and E is an acyl radical; and R is (CIC-IS) alkyl, which is benzyl or unsubstituted or substituted phenyl, wherein each of the two above radicals is unsubstituted or substituted, if appropriate after hydrolysis to aldehydes (R * = H) or ketones (R * = alkyl) of the formula (IV), S wi4f? n ^. ^.?. i ^? ^ j ^ - ^^ .. (IV) in which Z is OH or OX, or salts thereof under the conditions of a Strecker synthesis with ammonia / ammonium chloride and sodium cyanide and alternatively with a mixture of ammonia and cyanic acid or with ammonia and a salt of hydrocyanic acid, if appropriate in the presence of chloride ammonium, to give the a-aminonitriles of the formula (V) or a salt thereof, Adduct IV v.gr. NH3 / NaCN / NH4CI (V) wherein in the formulas (IV) and (V) the radical R * is as defined in the formula (I), X is as defined in the formula (IV-1) and Z in the formula (V ) is as defined in formula (IV) or is OH; and the compound of the formula (V) or a salt thereof is hydrolyzed under acidic or basic conditions to give the compound of the formula (I) or a salt thereof. * -v '^ "T ^ (P ^ í ** SHEET ANNEXE SUMMARY OF THE INVENTION According to the invention, glufosinates and their 2-methyl analogs are produced in a multi-step synthesis from methyl phosphorus compounds with keto unsaturated compounds (III) through adducts (IV), and the subsequent reaction in Strecker synthesis conditions and finally, hydrolysis of the aminonitplo (V): stage 1: (II) + (III)? adduct (IV); step 2: adduct (IV) for example NH3 / NaCN / NH4CL, (V); step 3: hydrolysis of (V) to glufosinates; several compounds are identifiable as adducts (IV), depending on the conditions of the method and the substrates. P00 / 121 F