Method for preparing n-phosphonomethylglycine and intermediate substance for its preparing

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing N-phosphonomethylglycine. Method involves interaction of derivative of hexahydrotriazine of the formula (II):

wherein X represents CN, COOZ, CH2OY and others; Z and Y represent hydrogen atom and others with triacylphosphite of the formula: P(OCOR3)3 (III) wherein R3 means (C1-C18)-alkyl or aryl that can be substituted. The prepared product is hydrolyzed and (if X represents CH2OY) oxidized. The proposed method is a simple in realization, economy and provides high degree of the end product purity.

EFFECT: improved preparing method.

19 cl, 11 ex

 

The present invention relates to a method for producing N-phosphonomethylglycine carried out by the interaction hexahydrotriazine connection with triarylphosphite, as well as intermediate products for use in this method.

N-phosphonomethylglycine (glyphosate) is a widely used herbicide solid (contact) actions. There are many ways to get phosphonomethylglycine. One such opportunity to obtain a reaction carried out by the interaction of derivatives hexahydrotriazine with esters of phosphorous acid. Thus, in particular, in patent US 4181800 described getting hexahydrotriazine formula

in the patent US 4053505 describes the interaction of these hexahydrotriazine with diesters of phosphorous acid and subsequent hydrolysis of the resulting product is obtained phosphonomethylglycine. However, it was found that both the yield and the selectivity of the actions require further improvements regarding manufacturerowned product. In addition, the diesters of phosphorous acid are extremely costly products.

In the application EP-A 104775 respectively in patents US 4425284, US 4482504 and US 4535181) describes the reaction is carried out by the interaction of the above hexahydrotriazine with with the missing allelochemical, and then Vospominanie using Trevira phosphorous acid and saponification with obtained phosphonomethylglycine according to the following scheme:

Although in this way phosphonomethylglycine and manages to obtain a relatively high yield, the method nevertheless along with the use of expensive esters of phosphorous acid also provides additional application of the acid chloride of the carboxylic acid. In addition, the possibility of recovery of acid chloride of the carboxylic acid optionally in the form of the free acid and the subsequent translation into a separate stage again in the acid chloride acid also significantly increases the cost method. In addition, it is not possible to fully recover the alcohol, which atrificial phosphorous acid, since during the reaction is equivalent to the corresponding alkylchloride, which among other things toxicologically unsafe.

In the patent US 4428888 (respectively, EP-A 149294) described the reaction is carried out by the interaction of the above hexahydrotriazine with the acid chloride of phosphorous acid in the presence of a strong anhydrous acid, for example hydrogen chloride, and C1-C6carboxylic acids, such as acetic acid. When carrying out this reaction formed numerous not podium is to be precise definition of by-products, reducing the output phosphonomethylglycine and causing significant costs to the purification of the resulting product.

In the patent US 4442044 describes the reaction is carried out by interaction hexahydrotriazine formula 5 with trifiro phosphorous acid results in the corresponding phosphonate compound used as a herbicide.

In DD-A 141929 and DD-A 118435 described reaction is carried out by the interaction of the alkali metal salt of the above hexahydrotriazine (R denotes, for example, Na) with W phosphorous acid. However, due to the principle of the poor solubility of salts of alkali metals is unable to achieve a satisfactory degree of chemical transformation.

In the patent US 5053529 describes getting phosphonomethylglycine interaction above hexahydrotriazine with treeframe phosphorous acid in the presence of titanium tetrachloride and subsequent saponification of the resulting product. However, the use of titanium tetrachloride significantly increases the cost of the process. In addition, the output of phosphonomethylglycine remains unsatisfactory.

In patents US 4454063, US 4487724 and US 4429124 describes getting phosphonomethylglycine the interaction of the compounds of formula

where R1and R2represent an aromatic or aliphatic gr is PPI with RCOX (X denotes Cl, Br, I) to obtain the compounds of formula

subsequent reaction of this compound with a metal cyanide and hydrolysis of the resulting product. The disadvantages of this method are connected, as in the above case, the application of a carboxylic acid.

The literature describes other ways of synthesis carried out on the basis of substituted cyanomethyl hexahydrotriazine formula

Thus, in particular, in patents US 3923877 and US 4008296 describes the reaction is carried out by interaction of this derived hexahydrotriazine with dialkylphosphate in the presence of an acid catalyst such as hydrogen chloride, Lewis acid, acid chloride or anhydride of carboxylic acid to obtain the compounds of formula

In the subsequent hydrolysis get phosphonomethylglycine, it is from 8 to 10% twice phosphonomethylglycine product.

In patents US 4067719, US 4083898, US 4089671 and in the application DE-A 2751631 described reaction is carried out by the interaction of substituted cyanomethyl hexahydrotriazine with diarylphosphino without the use of a catalyst to obtain compound (9), where R" represents aryl. This method has the same drawbacks as in the case of applying replaced by carboxypropyl hexahydro the triazine in the above formula 5.

In the application EP-A 097522 respectively in patents US 4476063 and US 4534902) describes the reaction is carried out according to the diagram below, the interaction hexahydrotriazine 6 allelochemical getting connection 10, further Vospominanie using Trevira or diapir phosphorous acid to obtain compound (11) and the final saponification getting phosphonomethylglycine

This version is characterized by the same disadvantages that are inherent to the method, which used replaced by carboxypropyl derivatives hexahydrotriazine.

In conclusion, it should be called the patent US 4415503, which describes the transformation of substituted cyanomethyl hexahydrotriazine similar to the way presented in the patent US 4428888. In this case also there is a significant formation of by-products.

In the application EP 164923 AND describes better the hydrolysis of compounds of formula 11.

With regard to the foregoing, the present invention was based on the task of developing a simple and economical way of obtaining phosphonomethylglycine, which among other things would provide a high degree of purity of the target product.

Unexpectedly, it was found that the above problem can be solved by interaction derived hexahydrotriazine t is allfashion and subsequent saponification of the resulting product to obtain the result desired phosphonomethylglycine.

In accordance with this present invention relates to a method for producing N-phosphonomethylglycine, namely, that

a) derived hexahydrotriazine formula II

in which

X represents CN, COOZ, CONR1R2or CH2OY, where

Y represents H or a residue, easily replaceable on N,

Z represents H, alkali metal, alkaline earth metal,

With1-C18alkyl or aryl, optionally substituted C1-C4the alkyl, NO2or

OC1-C4the alkyl,

R1and R2that may have identical or different meanings, denote N

or1-C4alkyl,

subjected to interaction with triarylphosphite formula III

in which the radicals R3can have identical or different meanings and denote With1-C18alkyl or aryl, optionally substituted C1-C4the alkyl, NO2either OS1-C4the alkyl, to obtain the compounds of formula I

in which R3and X have the above values, and

b) the compound of formula I hydrolyzing and, if X represents CH2OY, oxidizes.

The invention further relates to compounds of formula I, as well as to receive them according stud and a) method of obtaining phosphonomethylglycine.

Under the alkyl refers to an unbranched or branched alkyl chain preferably 1-8 carbon atoms and especially with 1-4 carbon atoms. As examples of the alkyl can be called methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-hexyl, 2-ethylhexyl, etc.

Under the aryl refers preferably phenyl and naphthyl.

X preferably represents CN or COOZ.

Z preferably represents H, alkali metal, or C1-C18alkyl.

If Y is a residue, easily replaceable on N, we mean preferably aliphatic or aromatic acyl residue or C1-C6an alkyl group. Aliphatic residue preferably represents C1-C6-CO-residue, and an aromatic acyl residue represents preferably benzoyl.

R1and R2denote preferably N.

R3especially preferably represents an aryl residue, which is optional, as indicated above, may be substituted. Especially preferred values of R3are phenyl, n-tolyl and n-nitrophenyl.

The compounds of formula II are known and can be obtained in a known manner or analogously to known methods (see, for example, the above prior art). So, h is particularly Amin X-CH2-NH2can be subjected to interaction with a source of formaldehyde, such as an aqueous solution of formalin or paraformaldehyde, for example, dissolving a primary amine in an aqueous solution of formalin. Required hexahydrotriazine can then be obtained by crystallization or evaporation of the water. This method is described in the application DE-A 2645085, respectively, in patent US 4181800, the publication in full included in the present description by reference.

The compounds of formula II in which X represents CN, can be obtained by the reaction of Strecker, i.e. the interaction of ammonia, hydrocyanic acid and a source of formaldehyde. A method of this type is described, for example, in patent US 2823222, which fully included in the present description by reference.

The compounds of formula III can be obtained in several ways. One such opportunity is the reaction carried out by interaction of the corresponding salts of carboxylic acids R3COOH with trihalogen phosphorus, primarily trichloride phosphorus. As a salt of carboxylic acid used is preferably the salt of an alkaline or alkaline-earth metal, especially sodium, potassium or calcium, or ammonium salt. The above reaction can be conducted without using a solvent and the resulting direct product is about to be applied at the stage a). Preferably, however, to work in an inert organic solvent, especially in a simple ether, such as dioxane, tetrahydrofuran and the like, halogenated, especially 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-tetrachlorethane, chlorobenzene or 1,2-dichlorobenzene, aliphatic or aromatic hydrocarbon, such as n-octane, toluene, xylene or nitrobenzene. It is preferable to use the same solvent as provided for stage a). Particularly preferable to use chlorinated hydrocarbons.

Formed by the reaction salt, for example sodium chloride in the case of trichloride phosphorus and sodium salt applied carboxylic acid, upon completion of the reaction can be removed. If you get salt ammonium chloride or other halide ammonia, the ammonia can recover by setting the pH of the aqueous solution of the salt of a strong base, for example sodium hydroxide, alkaline value (pH 11-14) and subsequent distillation of the ammonia in the usual way. The resulting ammonia after drying, for example by distillation to a liquid or gaseous state or in aqueous solution can again be returned to the process cycle and what to use to obtain the ammonium salt of carboxylic acid.

Another possibility of obtaining compounds of the formula III is that the carboxylic acid R3COOH is subjected to interaction with trihalogen phosphorus in the presence of an appropriate amine. As an amine is used primarily aliphatic or cycloaliphatic di - or triamine, such as triethylamine, tributylamine, dimethylethylamine or dimethylcyclohexylamine, and pyridine. As a rule, in the way of this type work in an organic solvent. Suitable for use in these purposes, the solvents mentioned above for the first variant obtain the compounds of formula III. Preferably dioxane, 1,2-dichloropropane, 1,2-dichloroethane, nitrobenzene or toluene. When using the solvent of the resulting amine hydrochloride precipitates and can be filtered. When processing hydrochloride amine strong base, for example aqueous sodium hydroxide solution, amines are allocated in a free form of the hydrochloride. Volatile amines can then recover by distillation or extraction. Non-volatile amines can recover by extraction or in the case of education in the allocation of amines two-phase mixture by phase separation, solid amines can recover by filtration. Recovered amines, optionally after drying, can be returned to the process and conduct the Horno be used in the method.

In another embodiment, obtaining the compounds of formula III interact carboxylic acid R3COOH with trihalogen phosphorus, primarily trichloride phosphorus, without added base. When carrying out this reaction, the resulting halogenated must be removed from the reaction mixture. This operation can be performed in the usual manner, for example by passing a stream of inert gas, such as nitrogen. Selected in free form halogenation can then be used in aqueous solution for hydrolysis in stage b).

Stage a) of the method according to the invention can be performed using a solvent or without, for example in the melt. Preferably, however, to use an inert organic solvent, for example hydrocarbons, such as toluene or xylene, a simple ether, such as tetrahydrofuran, dioxane or disutility ether. Especially, it is preferable to work in a halogenated solvent, particularly in chlorinated, preferably 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-tetrachlorethane, chlorobenzene or 1,2-dichlorobenzene. Components of the reaction are useful in a predominantly stoichiometric quantities. However, one or the other component m which should be used with some excess, for example up to 10%. The reaction temperature is usually in the range from -10 to +140°C, preferably in the range from room temperature to 100°C. When these conditions are met, the reaction requires only a short period of time, as a rule, the reaction is largely completed after 10-30 minutes

Obtained in stage a) the compounds of formula I are important intermediates for obtaining phosphonomethylglycine. With this purpose, the compounds of formula I is subjected to hydrolysis, which can be carried out in acidic or alkaline conditions, preferably acid hydrolysis. As the acid used in this primarily inorganic acids such as hydrochloric acid, sulfuric acid or phosphoric acid. Alkaline hydrolysis is carried out usually using hydroxides of alkaline or alkaline earth metals, especially sodium hydroxide or potassium.

The hydrolysis is expediently be performed using aqueous acid or base. When this aqueous acid or base, generally added to the reaction mixture obtained in stage a). The hydrolysis can be carried out without solvent or in the presence of a miscible with water, partially miscible or not miscible with water and inert organic solvent. It is preferable to use Rast is oritel, used in stage a). In the case of the use of the solvent at the stage a) obtained at this stage (a) reaction mixture, if necessary after removal, for example by distillation of part of the solvent, it is advisable to use directly. However, there is another approach, namely: used in stage a) the solvent to be removed completely and the residue is subjected to hydrolysis. Recuperated from the reaction mixture, the solvent can be reused in obtaining compounds of formula III or stage a).

Especially, it is preferable to carry out the hydrolysis in a two-phase system (aqueous phase/organic phase). Using partially miscible with water or not miscible with water, an organic solvent, preferably a hydrocarbon, such as toluene or xylene, a simple ester, such as dibutylamine the air, but first of all halogenated hydrocarbons mentioned above as solvents for stage a). The hydrolysis is carried out by intensive mixing of the two phases using the normal for these purposes, a device such as a reactor with a stirrer, a circulating reactor or preferably a mixer without additional mixing devices. Upon completion of hydrolysis of the phases are separated and subjected to the following processing.

Particularly preferred variant is Tom the execution of the invention is a method, in which stage a) is carried out in halogenated solvent, the solvent is optionally partially removed and the resulting compound of formula I is subjected to hydrolysis by processing obtained in stage a) of the reaction mixture of aqueous acid or base.

According to another variant, the hydrolysis of the compounds of formula I in obtaining phosphonomethylglycine can be made by enzymatic, for example, by using esterase and nitrilase.

Acid or base hydrolysis is used in at least equivalent amounts, preferably, however, in excess, especially in the amount of not less than 2 equivalents.

The temperature at which conduct the hydrolysis is typically in the range of from about 10 to 180°C, preferably from 20 to 150°C.

If X represents CH2OY, the resulting hydrolysis product is necessary to oxidize. When this comes primarily from the compounds in which X represents CH2HE. Oxidation to phosphonomethylglycine carry out the usual, well-known experts in this field, for example by catalytic dehydrogenation in the presence of copper catalysts.

If X represents CH2OY, where Y represents an acyl residue, while hydrolysis of the product from stage (a) the acyl OST the current otscheplaut with the formation of the corresponding compounds in which X represents CH2HE, then this compound is oxidized as described above to phosphonomethylglycine.

If X represents CH2OY, where Y is an alkyl residue, ether cleavage usually occurs simultaneously in the conditions of acid hydrolysis of the product from stage a). The compound obtained, where X denotes CH2HE, oxidized, as described above, to phosphonomethylglycine.

Obtained by hydrolysis using an excess of acid or base phosphonomethylglycine presented in dissolved form in the aqueous phase. Carboxylic acid R3COOH is formed by hydrolysis using an excess of acid directly, and when the main hydrolysis - after acidification of a strong acid, preferably until reaching pH values<0.5 in. Then the carboxylic acid is separated in the usual manner, for example by filtering off of this acid, precipitated in solid form in the sediment, by distillation or extraction is not miscible with the aqueous phase with an organic solvent. For two-phase hydrolysis of carboxylic acid under certain conditions provided in dissolved form in the organic phase. In these cases, the carboxylic acid is removed, separating the organic phase, after which it can, if necessary, to recover from the last in the usual way. Acid get high is the degree of purity and can be used again to obtain the compounds of formula III. Forming the organic phase, the solvent can be returned to the process cycle and re-used to obtain compounds of the formula III or stage a). Previously, however, the solvent in order to remove impurities, such as water-soluble or water-insoluble alcohols, phenols, ammonium salt and/or carboxylic acids are, as a rule, distillation, extraction, filtration and/or evaporation.

Phosphonomethylglycine can be precipitated by setting the pH of the aqueous phase to a value from 0.5 to 2.0, especially from 0.8 to 1.5, for example, by adding an appropriate acid or base, such as HCl, H2SO4or NaOH, KOH, CA(Oh)2and not necessarily by concentrating the aqueous phase and/or the addition of auxiliary precipitation reagent and get it (phosphonomethylglycine usual manner, for example by filtration. As a subsidiary of precipitation reagent preferably not miscible with water, the solvent, such as methanol, ethanol, isopropanol, acetone and other Solvents can recover from the mother liquor by distillation and then reuse them.

Formed during the saponification ammonia or ammonium chloride can be returned in a way, by establishing, under certain conditions, alkaline pH and recovery of ammonia by distillation.

If necessary, the resulting phosphonomethylglycine can normally discolor. This operation can be performed by processing small amounts of decolourizing agent, such as an oxidant, such as perborate or H2About2or adsorbents, such as activated carbon. The number of decolourizing agent depends on the degree of discoloration and can be defined by experts in the field in a simple way. Processing decolorizing agent can be in any location on completion of the hydrolysis and simple methods. It is advisable to add decolorizing means to deposition phosphonomethylglycine.

Proposed in the invention method, respectively, each of its stages, as such, can be performed in a continuous, periodic or properities mode. For these purposes, use an ordinary reaction vessel such as a reactor with a stirrer, a tubular reactor, if necessary, placed in front of them mixing devices or embedded in a tubular reactor mixing elements.

Thus, the proposed invention the method is characterized by simplicity in the implementation process and the use of inexpensive starting materials. The disadvantage of this method lies in the education going to waste neorganicheskoi. As protective groups, namely acyl residues triarylphosphite formula III, they can easily return in the process. The method allows to obtain phosphonomethylglycine at extremely short duration of the reaction and high yield of over 90% based on hexahydrotriazine formula II.

Below the invention is explained in more detail by way of examples, which in no way limit its scope.

Example 1

to 0.2 mole of Na-benzoate under conditions preventing access of moisture, pre-placed at room temperature in 50 ml of 1,4-dioxane. Then added dropwise 0,0667 mol of trichloride phosphorus and the mixture stirred for 20 min at 85°C. this forms a colorless suspension. Next add 0,0222 mole hexahydrotriazine 6 and the mixture continued to be stirred for additional 20 min at 85-90°With (liquid suspension with good peremeshivaemogo). Then the dioxane is distilled off at 40°With vacuum. To the residue was added 100 ml of concentrated hydrochloric acid for 4 h heated under reflux. After cooling, benzoic acid is filtered, followed by washing (a small amount of cold water) and drying. The combined filtrates evaporated to dryness. To highlight phosphonomethylglycine the residue from evaporation was dissolved in a small amount of water and precipitated in the cold to what t NaOH to achieve a pH of 1.5. Full deposition of reach by adding a small amount of methanol. In conclusion, phosphonomethylglycine filtered and dried.

Yield: 10.3 g of phosphonomethylglycine (purity, 95.3 per cent according IHVR), which corresponds to a yield of 91% based on PCl3. In the mother solution in the crystallization contains a further 1.8 wt.% phosphonomethylglycine.

Example 2

to 0.2 mole of Na-benzoate under conditions preventing access of moisture, pre-placed at room temperature in 50 ml of 1,4-dioxane. Then added dropwise 0,0667 mol of trichloride phosphorus and the mixture stirred for 20 min at 85°C. this forms a colorless suspension. Next, filter, excluding the access of moisture, and the residue is washed with a small amount of dioxane. To the filtrate, while continuing to exclude the access of moisture, add 0,0222 mole hexahydrotriazine 6 and the mixture is stirred for 20 min at 85-90°C. Then the dioxane is distilled off at 40°With vacuum. To the residue was added 100 ml of concentrated hydrochloric acid for 4 h heated under reflux. After cooling, the precipitated precipitated benzoic acid was filtered off, and then carry out the washing (small amount of cold water) and drying. The combined filtrates evaporated to dryness. To highlight phosphonomethylglycine the residue from evaporation was dissolved in a small amount of water and the wasp is give in the cold by the addition of NaOH to achieve a pH of 1.5. Full deposition of reach by adding a small amount of methanol. In conclusion, phosphonomethylglycine filtered and dried.

Yield: 10.5 g phosphonomethylglycine (purity 94,1% according IHVR), which corresponds to a yield of 93% based on PCl3. In the mother solution in the crystallization contains another 1.9 wt.% phosphonomethylglycine.

Example 3

To a solution of 0.04 mole hexahydrotriazine 6 in 80 ml of dioxane is added at room temperature a solution of 0.12 mol of createinvoice in 50 ml of dioxane. Solution for 2 h and stirred at 100°C, after which the solvent is distilled first at 40°under normal pressure and then under vacuum. To the residue was added 100 ml of concentrated hydrochloric acid for 4 h heated under reflux. Next, the reaction mixture is evaporated to dryness. To highlight phosphonomethylglycine the residue from evaporation was dissolved in a small amount of water and precipitated in the cold by the addition of NaOH to achieve a pH of 1.5. Full deposition of reach by adding a small amount of methanol. In conclusion, phosphonomethylglycine filtered and dried.

Output: 15,4 g phosphonomethylglycine (purity, 98.7 per cent according IHVR), which corresponds to a yield of 76% based on PCl3. In the mother solution in the crystallization contains another 1.6 wt.% phosphonomethylglycine.

When is EP 4

In the mixing flask with a volume of 2 l, equipped with a paddle stirrer (with blades made of Teflon) and a reflux condenser, pre-placed 284 g of the benzoate of ammonia in 1000 ml of 1,2-dichloroethane and in nitrogen atmosphere for 30 min added dropwise 91,5 g trichloride phosphorus. Temperature increases up to a maximum of 36°C. Then stirring is continued for another 30 min at 25-36°C. the mixture is filtered through a pressure suction filter and the filter cake washed twice more in an atmosphere of nitrogen dichloroethane portions 500 g (2054 g of the filtrate).

The filtrate is pre-loaded at room temperature in the mixing flask with a volume of 2 l, equipped with a paddle stirrer (with blades made of Teflon) and a reflux condenser, and add 45,54 g hexahydrotriazine 6. With stirring, heated for 30 min to 80°and continue to stir for 30 min at 80°C. Then the solution is allowed to cool, and then directly hydrolyzing.

With this purpose, the substance used load metered portions at 130°and a pressure of 8 bar in a tubular reactor (volume of about 600 ml) placed before him by the mixer without additional mixing devices (1265 g/h of a solution of dichloroethane from the previous stage, 207 g/h 20%HCl). Duration of stay of the material in the machine is 30 minutes First (grown the th) shoulder strap drop. For further processing of the received two-phase mixture catches for 60 minutes and Then the phases are separated at 60°and the aqueous phase is twice extracted with dichloroethane portions 100,

In a round bottom flask with a paddle stirrer (with blades made of Teflon) first transmission for 1 h stream of nitrogen at 60°With distilled residues contained in the aqueous phase of dichloroethane, and then for 15 min with 50%caustic soda at 40-60°To establish the pH at a value of 1.0. Then the resulting suspension is stirred for further 3 h at 40°C, cooled to room temperature, precipitated precipitated product is filtered vacuum-filtered and finally washed with 150 g of ice water. The obtained solid substance for 16 h and then dried at a temperature of 70°and a pressure of 50 mbar.

Output: 54.6 g of phosphonomethylglycine (purity of 96.2% according IHVR), which corresponds to a yield of 80% in terms of PCl3. In the mother solution in the crystallization contains another 2.1 wt.% phosphonomethylglycine.

Example 5

From the remainder of the ammonium chloride formed during the synthesis of tributylphosphite in example 4, to prepare a saturated solution in water. This solution combined with the mother liquor in the crystallization of phosphonomethylglycine according to example 4 and the excess caustic soda pH is adjusted to EIT is a group of 14. Then the ammonia flow of nitrogen is distilled off from the reaction mixture and analysis of the gas trap with GC (purity 99%). United dichlorethane phase of stage saponification dried by azeotrope distillation dichloroethane/water. In dichloroethane served dry ammonia until complete conversion of benzoic acid in ammonium benzoate and the resulting suspension of ammonium benzoate in 1,2-dichloroethane reuse in the synthesis process.

The output (recycling): 54,0 g phosphonomethylglycine (purity 97,0% according IHVR), which corresponds to a yield of 79% in terms of PCl3.

The output (second recycling): 55,1 g phosphonomethylglycine (purity, 95.5% of under IHVR), which corresponds to a yield of 81% in terms of PCl3.

Example 6

The reaction is carried out analogously to example 1, however, the difference is that as the solvent instead of 1,2-dichloroethane using nitrobenzene.

Output: 56,2 g phosphonomethylglycine (purity, 97.4% of under IHVR), which corresponds to a yield of 82% based on PCl3. In the mother solution in the crystallization still contains 2.0 wt.% phosphonomethylglycine.

Example 7

The reaction is carried out analogously to example 4, however, differs in that the solvent instead of 1,2-dichloroethane using 1,2-dichloropropan.

Output: 54,0 g phosphonomethylglycine (purity 96,92% according IHVR), which corresponds to a yield of 79% in terms of PCl3.IN the mother solution in the crystallization contains another 2.1 wt.% phosphonomethylglycine.

Example 8

The reaction is carried out analogously to example 1, however, the difference is that as the solvent instead of dioxane use of 1,2-dichloroethane. Phosphonomethylglycine in this embodiment is obtained in a yield of 75%.

Example 9

The reaction is carried out analogously to example 1, however, the difference is that as the solvent instead of dioxane using toluene. Phosphonomethylglycine in this embodiment is obtained in yield 68%.

Example 10: Getting phosphite from carboxylic acid, amine and PCl3

0.05 m of trichloride phosphorus in 15 ml of toluene are added dropwise at 0°With the solution of 0.15 mol of benzoic acid and 0.15 mol of dimethylcyclohexylamine in 90 ml of toluene. Further stirred for 15 min at 0°and then left to warm to room temperature. Precipitated precipitated hydrochloride is filtered off, excluding the access of moisture, through a pressure suction filter. Characteristics of tributylphosphite (yield 99%) was determined by analysis of the filtrate by the method1H-NMR and31P-NMR. If the residue obtained after distillation of the toluene from the filtrate, dissolving 0.15 mol of 10%NaOH, then by phase separation and subsequent extraction with toluene is possible to ensure the recovery of dimethylcyclohexylamine with quantitative yield.

Example 11

to 0.2 mole of Na-benzoate at room temperature, eliminating the access of moisture, pre-placed in a 50 m is 1,4-dioxane, then added dropwise 0,0667 mol of trichloride phosphorus and the mixture stirred for 20 min at 85° (colorless suspension). Then add 0,0222 mole hexahydrotriazine 1 (X denotes CN) and the mixture continued to stir for 20 min at 85-90°With (liquid suspension, mix well). Further, the dioxane is distilled off at 40°in vacuum, to the residue was added 100 ml of concentrated hydrochloric acid and heated for 4 h under reflux. After cooling, benzoic acid is filtered off and washed with small amount of water). The combined filtrate extracted twice with toluene portions 30 ml, centrifuged prior to the formation of dry residue and to remove excess hydrochloric acid, centrifuged three more times with ethanol. Toluene phase is concentrated and the residue combined with recovered benzoic acid.

To highlight phosphonomethylglycine from the remainder of the aqueous phase, the latter is dissolved in a small amount of water to precipitate in the cold at pH 1.0 (addition of NaOH). Complete precipitation is achieved by adding small amounts of methanol, which Recuperat from the mother liquor by distillation. The output is 91%.

Recovered benzoic acid (0,2 mol, purity above 99% according IHVR) dissolved in 0.2 mol 5%NaOH, then water distillate is ut and the residue is dried. Thus obtained sodium benzoate together with recovered by re-dioxane is used in the synthesis process.

The output (recycling): 90%,

the output (second recycling): 84%,

output (third recycling): 88%.

1. The method of obtaining N-phosphonomethylglycine, characterized in that a) derived hexahydrotriazine formula II

in which X represents CN, COOZ, CONR1R2or CH2OY, where

Y represents H, an aliphatic or aromatic acyl residue or C1-C6alkyl group,

Z represents H, alkali metal, alkaline earth metal, With1-C18alkyl or aryl, optionally substituted C1-C4the alkyl, NO2or OS1-C4the alkyl,

R1and R2that may have identical or different meanings, denote H or C1-C4alkyl,

subjected to interaction with triarylphosphite formula III

in which the radicals R3can have identical or different meanings and denote With1-C18alkyl or aryl, optionally substituted C1-C4the alkyl, NO2or OS1-C4the alkyl, and

b) hydrolyzing the resulting product, and, if X represents CH2OY, islet.

2. The method according to claim 1, in which X represents a CN or COOZ.

3. The method according to claim 1 or 2, in which R3represents phenyl, optionally substituted C1-C4the alkyl, NO2or OC1-C4the alkyl, or CH3.

4. The method according to any of the preceding paragraphs, in which stage a) is carried out in an organic solvent.

5. The method according to claim 4, in which the solvent used dioxane or tetrahydrofuran.

6. The method according to claim 4, in which the use of chlorinated organic solvent.

7. The method according to claim 6, in which the solvent used is 1,2-dichloroethane.

8. The method according to any of the preceding paragraphs, in which the compounds of formulas II and III are mainly used in equivalent quantities.

9. The method according to any of the preceding paragraphs, in which the compound of formula III is produced by interaction of the carboxylic acid of formula IV

in which R3matter specified in claim 1, or a salt thereof with trihalogen phosphorus.

10. The method according to claim 9 in which the salt is an alkali metal or ammonium salt of the carboxylic acid of formula IV is subjected to interaction with a halide of phosphorus.

11. The method according to claim 9, in which the carboxylic acid of formula IV is subjected in the presence of an appropriate amine interaction with a halide of phosphorus.

12. The method according to p., in which the carboxylic acid of formula IV is subjected to interaction with a halide of phosphorus without the use of reason.

13. The method according to any of PP-12, in which the reaction is carried out in an inert organic solvent selected from the group of aromatic or aliphatic hydrocarbons and chlorinated hydrocarbons.

14. The method according to item 13, in which the solvent after the reaction Recuperat and return to the process cycle.

15. The method according to claim 1, in which the product obtained in stage a)hydrolyzing in the presence of the appropriate aqueous acid.

16. The method according to item 15, in which the hydrolysis is carried out in a two-phase system.

17. The method according to clause 16, in which phosphonomethylglycine precipitated from the aqueous phase by establishing a pH of from 0.5 to 2.0.

18. The method according to 17, in which the deposition of phosphonomethylglycine carried out in the presence of mixing with the water solvent.

19. The intermediate product obtained by the interaction derived hexahydrotriazine formula II

in which X represents CN, COOZ, CONR1R2or CH2OY, where

Y represents H, an aliphatic or aromatic acyl residue or1-C6alkyl group.

Z represents H, alkali metal, alkaline earth metal, With1-C18alkyl and is, and aryl, optionally substituted C1-C4the alkyl, NO2or OS1-C4the alkyl,

R1and R2that may have identical or different meanings, denote H or C1-C4alkyl,

subjected to interaction with triarylphosphite formula III

in which the radicals R3that may have identical or different meanings, denote With1-C18alkyl or aryl, optionally substituted C1-C4the alkyl, NO2or OS1-C4the alkyl.



 

Same patents:

FIELD: chemistry of organophosphorus compounds.

SUBSTANCE: invention relates to compounds with the bond C-P, namely to phosphorus-boron-containing methacrylate that can be used as inhibitor of combustion of polyvinyl alcohol-base film materials. Invention describes phosphorus-boron-containing methacrylate of the following formula: wherein n = 4-8. Polyvinyl alcohol films modified with indicated phosphorus-boron-containing methacrylate shows the enhanced refractoriness, rupture strength up to 206 kgf/cm2, water absorption up to 240% and relative elongation up to 12%.

EFFECT: valuable properties of substance.

1 tbl, 2 ex

FIELD: organic chemistry, in particular improved method for production of phosphorinated and chlorinated methacrylates.

SUBSTANCE: invention relates to method for production of compounds having general formula , wherein R is lower alkyl and R1 is lower alkoxyl, phenoxyl, or group of formula . Claimed method includes reaction of pentavalent phosphorous acid chloroanhydride with glycydil methacrylate at 20-50°C in presence of titanium tetrachloride as catalyst in amount of 0.02-0.05 % calculated as reagent mass.

EFFECT: one-step method for production of phosphorous and chlorine containing methacrylates with improved water resistance.

2 tbl, 7 ex

The invention relates to new biologically active phosphonate derivative of acyclovir

The invention relates to the chemistry of organophosphorus compounds, and in particular to a new method of obtaining N-substituted phosphorylated of imidates having the structure zenatello group

The invention relates to derivatives of phosphinic and phosphonic acids of the formula (I)

where R1means unsubstituted or substituted phenyl, -O-(C1-C6)-alkyl, R2means hydrogen, RR3mean hydrogen, alkyl, unsubstituted or substituted phenyl, COOH group or - (CH2)2-CH(COOH)-NH-SO2-C6H4-C6H4-Cl(n), t stands for an integer of 1-4, And is a covalent bond, X is a group-CH=CH -, - group,- (CH2)about- where is 0,1,2 or 3, Y1and Y2mean-OH, -(C1-C4)-alkyl, -O-(C1-C4)-alkyl, and/or their stereoisomeric forms and/or physiologically acceptable salts

The invention relates to new derivatives of benzazepine-N-acetic acid, substituted phosphonic acid, which are pharmaceutically active compounds

The invention relates to new derivatives of anhydride methylenephosphonic acid of the formula I, where Y1, Y2, Y3and Y4group OR1, NR2R3, OCOR1, OCNR2R3, O(CO)OR1, O(SO2R1or OP(O)R2(OR3), where R1, R2and R3- H, C1-22alkyl, aryl, possibly substituted, or SiR3where R3- C1-C4alkyl, provided that at least one of the groups Y1, Y2, Y3and Y4other than the group OR1or NR2R3, Q1and Q2Is H, F, Cl, Br, I, methods of obtaining these new compounds as well as pharmaceutical preparations containing these new compounds

The invention relates to organic chemistry, particularly to a method of obtaining N-substituted alkyl-(2-dialkoxybenzene)alkylamides, which are a new structural type of organophosphorus compounds

The invention relates to chemistry, particularly to a method of obtaining N-acylated alkyl-(2-acetyl-2-dialkoxybenzene)ethanamide, which are a new structural type of organophosphorus compounds

FIELD: organophosphorus compounds, medicine.

SUBSTANCE: invention relates to new biologically active phosphonate compounds. Invention describes phosphonate compound of the formula:

wherein R1 and R'1 represent independently hydrogen atom (-H) substituted possibly with -O-(C1-C24)-alkyl, -O-(C1-C24)-alkenyl, -O-(C1-C24)-acyl, -S-(C1-C24)-alkyl, -S-(C1-C24)-alkenyl or -S-(C1-C24)-acyl wherein at least one among R and R'1 doesn't represent -H and wherein indicated alkenyl or acyl comprise from 1 to 6 double bonds; R2 and R'2 represent independently -H substituted possibly with -O-(C1-C7)-alkyl, -O-(C1-C7)-alkenyl, -S-(C1-C7)-alkyl, -S-(C1-C7)-alkenyl, -O-(C1-C7)-acyl, -S-(C1-C7)-acyl, -N-(C1-C7)-acyl, -NH-(C1-C7)-alkyl, -N-((C1-C7)alkyl)2, oxo-group, halogen atom, -NH2, -OH or -SH; R3 represents phosphonate derivative of nucleoside or biphosphonate; X represents compound of the formula:

L represents a valence bond or a bifunctional binding molecule of the formula: -J-(CR2)t-G- wherein t is a whole number from 1 to 24; J and G represent independently -O-, -S-, -C(O)O- or -NH-; R represents -H, unsubstituted or substituted alkyl or alkenyl; m means a whole number from 0 to 6; n = 0 or 1. Also, invention describes pharmaceutical compositions comprising phosphonate compounds, method for treatment of osteoporosis in mammal, method for increasing mineral osseous density, method for prophylaxis of apoptosis of osteoblasts and osteocytes in mammal, method for treatment of viral infection in mammal, method for treatment of growing neoplasm in mammal and method for proliferation of cells. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of phosphonate compounds.

17 cl, 2 dwg, 7 tbl, 21 ex

The invention relates to new and nitrate salts of compounds of formulas (I) to(VI), which can be used in medicine for the treatment of bone disorders such as abnormalities in bone and joints

New drug substances // 2237657
The invention relates to organic chemistry and can find application in medicine

New drugs // 2237057
The invention relates to organic chemistry and can find application in medicine

The invention relates to a method for dihydrate bis(1-hydroxyethane-1,1-diphosphonate(2-))cuprate(II) ammonium, which is as follows: dehydrate bis(1-hydroxyethane-1,1-diphosphonate(2-))cuprate(II) ammonium is produced by crystallization from a solution prepared by mixing the spent solution from the etching of printed circuit boards containing copper(II) and ammonia or ammonium salts, and 1-hydroxyethane-1,1-diphosphonic acid in an amount to provide a molar ratio of copper(II):1-hydroxyethane-1,1-diphosphonic acid 1.0:(2,0-4,0), and having a pH value preferably of 2.0 to 3.5

The invention relates to chemical technology of organophosphorus substances that can be used to prepare electrolyte galvanic and chemical abaltimore, as well as receive other organophosphorus substances, used as fertilizers in agriculture

The invention relates to the field of chemistry of organophosphorus compounds, in particular to an improved method for producing trinational the salt postemergency acid uranyl, which is carried out by reaction of sililirovanie phosphorous acid hexamethyldisiloxane taken at 1.5 to 2.5-fold excess of the stoichiometric required to monochloramine, subsequent similarobama and alkylation of intermediate reaction products undergo simultaneous introduction into the reaction mass hexamethyldisilazane in number, comprising 75-95% of the stoichiometric required, and alkylphosphonate, and saponification of Trevira postemergency acid is carried out in two stages, with the first stage using 20-70% stoichiometric alkali necessary, and the remaining amount of alkali - second stage

The invention relates to a method for producing bis(1-hydroxyethane-1,1-diphosphonate(1-)) copper(II), which relates to chemical technology of organophosphorus substances

The invention relates to derivatives of phosphinic and phosphonic acids of the formula (I)

where R1means unsubstituted or substituted phenyl, -O-(C1-C6)-alkyl, R2means hydrogen, RR3mean hydrogen, alkyl, unsubstituted or substituted phenyl, COOH group or - (CH2)2-CH(COOH)-NH-SO2-C6H4-C6H4-Cl(n), t stands for an integer of 1-4, And is a covalent bond, X is a group-CH=CH -, - group,- (CH2)about- where is 0,1,2 or 3, Y1and Y2mean-OH, -(C1-C4)-alkyl, -O-(C1-C4)-alkyl, and/or their stereoisomeric forms and/or physiologically acceptable salts

The invention relates to new derivatives of benzazepine-N-acetic acid, substituted phosphonic acid, which are pharmaceutically active compounds

FIELD: organophosphorus compounds, medicine.

SUBSTANCE: invention relates to new biologically active phosphonate compounds. Invention describes phosphonate compound of the formula:

wherein R1 and R'1 represent independently hydrogen atom (-H) substituted possibly with -O-(C1-C24)-alkyl, -O-(C1-C24)-alkenyl, -O-(C1-C24)-acyl, -S-(C1-C24)-alkyl, -S-(C1-C24)-alkenyl or -S-(C1-C24)-acyl wherein at least one among R and R'1 doesn't represent -H and wherein indicated alkenyl or acyl comprise from 1 to 6 double bonds; R2 and R'2 represent independently -H substituted possibly with -O-(C1-C7)-alkyl, -O-(C1-C7)-alkenyl, -S-(C1-C7)-alkyl, -S-(C1-C7)-alkenyl, -O-(C1-C7)-acyl, -S-(C1-C7)-acyl, -N-(C1-C7)-acyl, -NH-(C1-C7)-alkyl, -N-((C1-C7)alkyl)2, oxo-group, halogen atom, -NH2, -OH or -SH; R3 represents phosphonate derivative of nucleoside or biphosphonate; X represents compound of the formula:

L represents a valence bond or a bifunctional binding molecule of the formula: -J-(CR2)t-G- wherein t is a whole number from 1 to 24; J and G represent independently -O-, -S-, -C(O)O- or -NH-; R represents -H, unsubstituted or substituted alkyl or alkenyl; m means a whole number from 0 to 6; n = 0 or 1. Also, invention describes pharmaceutical compositions comprising phosphonate compounds, method for treatment of osteoporosis in mammal, method for increasing mineral osseous density, method for prophylaxis of apoptosis of osteoblasts and osteocytes in mammal, method for treatment of viral infection in mammal, method for treatment of growing neoplasm in mammal and method for proliferation of cells. Invention provides preparing new compounds eliciting useful biological properties.

EFFECT: valuable medicinal properties of phosphonate compounds.

17 cl, 2 dwg, 7 tbl, 21 ex

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