MXPA97009878A - Process for preparing n-fosfonometiliminodiacet acid - Google Patents

Abstract

A process for the preparation of N-phosphonomethyliminodiacetic acid is described. The process comprises simultaneously infusing a reaction mixture, water, an iminodiacetic acid source, a formaldehyde source, and a source of phosphorous acid and strong acid.

Description

PROCESS FOR PREPARING N-FOSFON ACID? PTILIÍ1INODIflCETICQ BACKGROUND OF THE INVENTION (1) Field of the invention The present invention relates to a method for the phosphonorne-t-alation of primary or secondary amines and, more particularly, to an improved process for preparing N-phosphonornethyl rninodi ceti co acid. (2) Description of the related art The N-phosphonornethyl rninodiacetic acid compound (NPMIDA) serves as an intermediary in the preparation of N-phosphonornet glycae (glyphosa + e) which is a large specie impor + before herbicide. The structure of NPMIDA is shown in formula I: In the past, NPMIDA was prepared from a source of hydradiatic acid (IDA) using multiple step procedures. I ??? The candidate is hydrolyzed to f > The rhinodacetyl-t-ryl (IDAN) is placed on an alkali metal base to form the dial-cal metal salt of the dianacetic cell (IDA). Both the IDA alkali metal salts and the IDA itself are used to prepare the NPMIDfl. and isolate the IDA of the TDAN hydrolyzate by acidification with a mineral acid (typically uric acid or hydrochloric acid), cp s-t at the IDA level, and filtration to recover the ADI. Then the IDA is used to prepare NPIUDA. For example, in the patent est doun teaching 3,? 88, R4F > , which is incorporated herein by reference, Iranian and co-inventors first formed the hydrochloric + or IDA salt from IDA, and then submitted it to phosphonornetilac on with phosphorous acid and null fo. In U.S. Patents 4,724,103 and 4,775,498, which are incorporated herein by reference, Gentilcore described a method that used the IDA-dodium salt (DSIDA) as the starting material for phosphonorheylation. The DSIDA was first reacted with hydrochloric acid to form the hydrochloride salt of IDA (IDA.HC1), and then by phospholornethylation with phosphorous acid and tormaldehyde to form the NPHIDA. Phosphorus trichloride served as a source of both hydrochloric acid and phosphorous acid. In the first step, the hydrolysis, phosphorous trichloride was hydrolyzed to phosphorous acid, while simultaneously converting the DSIDA to IDA. HCl and sodium chloride, according to the following general equations: I PCI3 + 3H20 > H3PO3 •• 3HC1 II Na2lDA + 2HC1 --- > IDA »2NaCl III IDA < • HCl < === - > GOING. HCl In the second step, the phosphorylation was added to the reaction mixture by phosphonorne-tllar IDA. HCl according to the following equation: IV H3PO3 + CH2O + IDA. HCl > (H0) 2-P (0) CH2N (CH2C00H) 2 + H2O + HCl In Example 2 of the '103 and' 498 patents, the two-step method was combined by combining a portion of the DSIDA and the entire PCI3 in the first step and then, in the second step of the reaction, adding formalin to phosphonorneneate , and also adding more Na2lDA, so that at least some of the formation of IDA-HC1 in the second reaction mixture occurred simultaneously with the phosphonorheylation reaction. However, none of the PCI3 was infused simultaneously with the DSIDA and the formal ina. In the existing intermittent procedures for the manufacture of NPMIDA, all the phosphorous acid and the strong acid catalyst, as well as the entire IDA are presumed to be added to the formal one and the remaining ADI. It is this approach, which was described in the '103 and' 498 patents, as well as the '845 patent approach have provided useful commercial procedures that achieve the desired phosphonation of the IDA to NPMTDA, at the same time that they reduce at least the undesirable side reactions that would produce N-ineti-1-acetic acid (NMTDA) and hydroxyrne-1-phosphonic acid (HMPA). However, the conventional method could be improved by developing a one-step process in which all the materials are added in a reaction mixture. Such a procedure could be adapted for a continuous synthesis of NP lDA and would provide a method that would simplify the production of NPMIDA and reduce the cost, energy consumption and quantity and complexity of the required manufacturing equipment, while at the same time providing a high level of product performance and minimum levels of undesirable byproducts.

BRIEF DESCRIPTION OF THE INVENTION In accordance with the present invention, it has been discovered that N-phosphonornetiiirninodiacetic acid can be produced from an IDA source by a one-step process, using a method comprising combining in a reaction mixture: water, a source of IDA, a source of formaldehyde, a source of oil and a source of oil; where the source of formaldehyde and the source of acid-phosphorus are dissolved in the reaction mixture. Surprisingly, this simplified procedure of a single step obtains the desired phosphomethylation reaction in a high yield, with minimal byproduct formation. The addition of the phosphorous acid source substantially at the same rate at which the source of formaldehyde is infused, reduces the amount of phosphorous acid present in the reaction mixture, as compared to that present in the reaction mixture. Two-stage procedure, currently in use. The lower concentration of phosphorous acid in the reaction mixture of the present process serves to decrease the amount of HHPA and NMIDA produced as undesirable byproducts. Thus, using the procedure described in greater detail below, it is found that the yield of N-fos fonometi limmodiacetic acid is unexpectedly high, with minimal production of undesirable byproducts. In addition, the present method can use various starting materials as IDA sources, including the IDA disodium salt, the IDA rnonosodium salt, the IDA itself or a strong mineral acid salt of the IDA. The present invention can also be used in a continuous process in which NP lDA is continuously removed from the reaction mixture, while the reactants are continuously added to the reaction mixture.

Thus, among the various advantages provided by the present invention, there is included the provision of a method for the "prosthesis" (NI NIULDA) in a one-step procedure, which is more efficient in cost and energy; the provision of a pat method to produce NPMTDA that is simpler and requires more manufacturing equipment, the provision of everything to produce NPIID in a high yield, without a substantial amount of byproduct production, and the provision of a mé odo pries the continuous production of NPMIDA.

DESCRIPTION OF THE PREFERRED MODALITIES The process of that invention provides a method by which a primary or secondary amine can be phosphonomethylated using a mixture of water, phosphorous acid, strong acid, formaldehyde and the primary or secondary amine. In particular, N-phosphonornetium-ammonium acetic acid can be produced by combining in a reaction mixture: water, a source of phosphorous acid, a source of strong acid, a source of mono-diacetic acid and a source of formaldehyde, wherein the source of The formaldehyde and the source of phosphorous acid are simultaneously infused into the reaction mixture. The reactions that take place are exemplified in the previous equations I-IV, using as starting materials: water, DSIDA, formaldehyde and PCI3, which serves both as a source of phosphorous acid and as a source of strong acid. These reactors are exemplary and are not intended to be quoted in a restrictive manner. Additionally, while the method of the invention is generally described here using DSIDA, other suitable sources of IDA can also be used. One of the goals obtained through the < The single stage of this is the production of NPMIDA in high yield, at the same time that the production of undesirable byproducts is minimized. An undesirable byproduct is HMPA, which is formed by the reaction of phosphorous acid with formaldehyde. The amount of HflPA is decreased by decreasing the relative amount of phosphorous acid present. It is believed that the present process obtains the reduction in the formation of HMPA by maintaining a lower concentration of phosphorous acid during the course of the reaction. The process of the present invention also decreases the relative production of HMPA by increasing the amount of free HCl, as reactive, present in the reaction mixture. The method of the present invention provides a gradual infusion of either HCl or PCI3 as a source of HCl, during the same period of time in which the reactive forms are added. Therefore, it is possible to avoid immediate production and mitigate the loss of excess HCl that is released. As a result, a higher concentration of free HCl is maintained throughout the reaction period. This, in turn, favors the formation of NPM1 A. This increase in the production of NPMTDA increases the relative production of NPMIDA with respect to the HMPA byproduct. Under certain conditions, the ADI and fopnaldehyde can react to form another undesirable byproduct, NMIDA. The production of NMIDA is minimized, maintaining sufficiently high levels of mineral acid, preferably HCl, in the reaction mixture. In the first place, as shown in equation II above, the strong acid, preferably hydrochloric acid, produces the acidic form of the IDA when an alkali metal salt of the acid is used. IDA as starting material, source of IDA. Secondly, the strong acid converts the IDA to the IDA salt with mineral acid, as shown in equation III, when an alkali metal salt of the IDA or the IDA itself is used as the starting material. A third function of the strong acid is to minimize the production of the undesirable by-product N-methylimino-diacetic acid (NMIDA). The inventors have discovered that the three cited functions of the strong acid are advantageously achieved by infusing a phosphorus halide or a mixture of a strong acid with phosphorous acid, simultaneously with the source of IDA and the forrn idehido. When using HCl as a strong mineral acid, the concentration of free HCl in the reaction mixture is on the scale from 0% to 20%, preferably, preferably at least about 5% by weight, calculated on the basis of HCl and H2O, only. As noted above, the process of the present invention maintains a high concentration of free HCl in the reaction mixture, as a result of the infusion of HCl during the same period of time in which the others are added. reagents This maintained a high level of acid, which results in a low yield of the undesirable byproduct, NMIDA. By infusing the source of phosphorous acid, it is possible to avoid the production of high concentrations of phosphorous acid in the reaction mixture. This reduces the amount of by-product produced, in particular- of HMPA and NMIDA. Accordingly, the present process allows high NPMIDA yields and low amounts of byproducts to be obtained, while a one-stage synthesis process is satisfactorily obtained. The yields are calculated as the ratio of the number of moles produced divided by the amount of the number of moles of the initial IDA source to the number of moles of IDA recovered after the reaction ends. More than 90% NPMIDA performance can be obtained using the present method. It is desirable that the phosphorous acid and the strong acid be provided to the reaction mixture from a single source, preferably, a phosphorus halide. Very JU preferable, it is PCI3, which forms phosphorous acid and hydrochloric acid when it reacts < on water, according to the mechanism indicated in equation I. Alternatively, phosphorous acid and a strong acid, such as sulfuric acid or hydrochloric acid, can be added simultaneously to provide the reactants to form an acid salt of IDA and for phosphonomot 1 lac 1 on (equations 1T- 1V). Tal < As used herein, the terms "strong acid" or "mineral acid" include inorganic mineral acids having a pKa of less than about 2.

Typically, said acids include: sulfuric acid, hydrochloric acid, brornhidpco acid, iodidic acid and the like. Hydrochloric acid is a strong source of acid, although any strong mineral acid can be used instead. As noted above, the present method can use various starting materials as IDA sources, for example, the IDA disodium salt (DSIDA), the TDA monosodium salt, the IDA itself, or a salt of TDA with strong mineral acid. The source of formaldehyde may include gaseous formaldehyde, an aqueous solution of gaseous formamide (formalin) or paraformaldehyde. A preferred source of formaldehyde is formalin. In general, the process of the present invention can be carried out at approximate temperatures of 85 to 200 ° C, and under pressure conditions from about 0 to about 4.21 1 g / cm2 manornet rj eos above the pressure environmental. For environmental conditions reference is made to the temperature and pressure that exist in the surrounding air, that is, approximately the room temperature and the normal pressure atmosphere. It is preferred that the temperature scale be from 5 ° C to 145 ° C. Very preferable is a temperature scale of 125 145 ° C, appro priately. Under ambient pressure, the reflux temperatures are around 105 ° C to around 115 ° C. However, it is preferred for the present process that the reaction be operated under increased pressure of about 0.35 to about 4.2 g / ern2 rich nanornet. A pressure of about 1.26 to 2.10 (-g / ern2) is highly preferable.The increased reaction temperature and the increased pressure above ambient pressure give a higher yield of MPMIDA, while producing less NMIDA by-product. When PCI3 is used as a source of phosphorous acid, the hydrolysis of POI3, shown in equation I, is an exothermic reaction.Therefore, the hydrolysis reaction can provide a source of heat- to maintain the reaction temperature. This provides such a high cost saving that the amount of heat required from an external source can be reduced.The simultaneous supply of reactants to the reaction mixture allows the conversion of IDA to NPMIDA in a high yield, with production I sub-products? undesirable. By simultaneous infusion or simultaneous supply it is meant that the addition of the reagents is approximately during the same period of time. Anyone skilled in the field will readily appreciate that this can be achieved by continuous reagent nfusion or by adding reagents in alternating and repeated quantities, or by any other means, as long as the reagents are added to the mixture. reaction during the phosphorylation reaction. In general, it is convenient that the delivery rate of each of the reactants be substantially the same, calculated on a molar basis with r-time. By substantially the same velocity it is meant, for example, that when all reagents are added simultaneously, the source of phosphoric acid, the source of strong acid and the source of formal ehi or, are supplied to the reaction mixture, each, at a speed on moles per number of times, which can be independently from around 80% to 140% of the supply speed of the IDA source. In one of the preferred modalities, the reaction vessel can be loaded initially with about 25% to 75% of the total IDA source to be added to the reaction vessel. When an initial amount of the IDA source is added to the reaction vessel, the rate of supply of the IDA source, subsequently, may be approximately 25% to 125% of the supply rate of 1 J the source of phosphorous acid or the source of formal dehyde, on a molar basis. In a variation of this embodiment, the reaction vessel can be charged with an initial amount of an IDA source in combination with an initial amount of a source of phosphorous acid. In another variation of this mode, the reaction vessel can be charged initially with a strong acid. After the reaction, the NPMTDA is recovered from the reaction mixture. The precipitation of NPMTDA can be facilitated-with emphasis. In order to recover additional amounts of the reaction liquid, a diluted base, such as sodium hydroxide, may optionally be added to the reaction mixture, to adjust the pH to the point of minimum solubility of NPMIDA. The water in the diluted base serves to solubilize the NaCl produced from the reaction of the base. The amount of base required is approximately equal to the HCl present in the reaction mixture, and whoever is skilled in the material can easily calculate it. The process of the present invention can be used in any reactor system known in the art, including intermittent reactors, continuous reactors or semi-continuous reactors. In an intermittent reactor the three reagents are added and the reactions are allowed to proceed; and during that time no product is extracted. In a continuous reactor the reactants are introduced and the products are extracted simultaneously, in a continuous manner. In a nuclear reactor, some of the reactants can be charged to the p? Inception, it is evident that this is continually being fed as the reaction proceeds. In such a way, the present invention can be advantageously used in a continuous or continuous flow reactor system such as, for example, in a tank reactor. In such a system, the reactor can be loaded with the DSIDA (or another source of TDA) and the POI3"followed by a continuous feed of AIDS (or another source of IDA), PCI3, formaldehyde and water. If an initial reaction period is carried out, a fraction of the reaction mixture is extracted from the tank reactor, as an effluent, on a continuous basis. The effluent can be cooled and, optionally, the pH can be adjusted to precipitate adi citonally the liquid compound. Then the precipitate is separated and recovered from the mother liquor. One of skill in the art will appreciate that numerous well known methods can be used to recover the NPMIDA precipitate. For example, the precipitate can be separated and recovered from the mother liquor. Anyone skilled in the art will appreciate that numerous well-known methods can be used to recover the NPMIDA precipitate. For example, the precipitate can be separated from the mother liquor by continuous filtration (see Chemical Engmeers' Handbook, 6th edition, Perry and Green, eds., McGraw-Hill, New York, chapter 19, pages 1-108, 1984, which is incorporated here as reference). When using DSIDA as l's Starting material or when a base, such as sodium hydroxide, is added, in order to precipitate precipitation, a salt is produced in the mother liquor, which, therefore, must be discarded. However, when IDA is used as starting material and no base is added to aid the recovery of dissolved NPMIDA, the mother liquor can be returned to the reactor. This recirculates any remaining NPMI A in the mother liquor, back into the reaction mixture and, finally, allows a greater recovery of the process. The above description 'generally describes the method of the present invention. A more complete understanding can be obtained by reference to the following specific examples, which describe preferred embodiments of the invention. Other modalities within the scope of the claims herein will be apparent to those of skill in the art, from consideration of the specification or practice of the invention, as described herein. It is intended that the specification, together with the examples, be considered as exemplary only, the scope and spirit of the invention being indicated by the claims that follow the examples. In the examples, all percentages are given on the basis of weight, at least as indicated otherwise.10 EXAMPLE 1 This example illustrates the preparation of NPMIDA from DSTDA, PCI3, formaldehyde and water, under increased ion and high temperature, with an initial charge of the reaction vessel with DSIDA and PCI3 - It is charged in a reactor of Cuba of two liters, equipped with condenser and mechanical agitator, 512 g of an aqueous solution (41.5%) of the disodium salt of the imidodiacetic acid 1 co. The reactor was brought to an internal temperature of 85 ° C and 173 g of PCI3 was added through the immersion tube for 28 minutes. The resulting mixture was transferred to a 2-liter reactor system, with pressure and temperature control, and brought to 85 ° C. Another 65 g of PCI3 was charged to the reactor. The reactor temperature was raised to 130 ° C (0.87 l-g / cm2) and the simultaneous PCI3 feeds were started (199 g for 44 minutes), 43.3% aqueous water (219 g for 60 minutes). ) and disodium salt of aqueous im-diacetic acid, at 41.5% (769 g for 54 minutes) to the reactor. During that portion of the reaction the temperature in the reactor reached a maximum of 131 ° C and the pressure was raised to 1.75 kg / cm 2 and kept therein. After all the feeds were complete, the reaction was allowed to proceed for 60 minutes, then cooled and filtered to give 596 g of N-phosphonornet? I? Nn? Nodyl acid to 99.6. The filtrate contained 1 r7 Others: 5 g of N-fos-ionimino diacetic acid and 27 g of irinodiane acid. This is a 97% yield of N-phosphonoinetiminodiacetic acid, based on the disodium salt of iminodiacetic acid not recovered.

EXAMPLE 2 This example invalidates the release of NPM1DA from DSIDA, PCI3, for-rn l clehi and water, at ambient pressure and reflux temperatures, with an initial drop in the reaction vessel with DSIDA and PCI3. To a reactor with a 2 liter jacketed tank, equipped with a condenser and mechanical stirring, 501 g of an aqueous solution (42.4%) of the di-hate salt of irenic acid was charged. The reactor was brought to an internal temperature of 85 ° C and 175 g of PCI3 was added through the immersion tube for approximately 30 minutes. The reactor temperature was raised to reflux (about 110 ° C) and simultaneous feeding of PCI3 (116 g for 24 minutes), 43.6% aqueous formaldehyde (165 g for 62 minutes), and sodium disodium salt were initiated. 42.4% aqueous nano-diacetic acid (334 g for 56 minutes) to the reactor. During this portion of the reaction the temperature in the reactor was maintained at reflux. After all the feeds were complete, and after a residence time of 60 minutes, the reaction was cooled and filtered to give 377 g of 98.3% N-phostonometiiyia non-acetic acid. The filtrate contained another 30 g of N-phosphonomet 11 iminodiacetic acid and 12 g of iminodiacetic acid. Fso is a yield of (-) 5% of N-phosphonornetide acid, based on the dieodium salt of the unrecovered nanoinodiacetic acid.

EXAMPLE 3 This example illustrates the preparation of NPMIDA from DSIDA, PCI3, aldehyde form and water, after an initial charge of the reaction vessel with HCl. 50 g of 37% HCl is charged in a 2 liter, jacketed tank reactor equipped with condenser and mechanical stirring. The solution was heated to reflux and the simultaneous feeding of the sodium salt of the uro-diacetic acid (832.5 g of aqueous solution at 42.5%), forrnaline (140.5 g of material at 47%) and PCI3 (283 g) was initiated. ). The disodium salt of the nninodiacet acid 1 co was fed for a period of 64 minutes, the PCI3 for 53 minutes and the forrnaline for 63 minutes. After all the feeds were completed, and a residence time of 60 minutes was maintained at reflux, the reaction was cooled and filtered to give 361 g of 98.5% N-phosphonornetiiirninodiacetic acid. The filtrate contained another 19 g of N-phosphonomethylimodialytic acid and 27 g of iminodiacetic acid. This is a yield of 93% N-phosphonornethylninodiacetic acid, based on the disodium salt of unrecovered iridium diacetic acid.

EXAMPLE 4 This example illustrates a repeated preparation in water of MPMIDA from IED, PCI3 and formaldehyde with an initial charge of the reaction vessel with IDA, HCl and water; elimination of NPMIDA after the reaction and recharge of mother liquor with TDA. A 2 liter, jacketed reactor, equipped with a condenser and mechanical stirring, charged 266 g of 1-amino diacetic acid, 194 g of concentrated HCl and 358 g of H 2 O. The solution was heated to 103 ° C and the simultaneous feeds of PCI3 and formalma were started. The PCI3 (291 g) was fed over a period of 50 minutes and the formal ina (153 g of 47% material) was fed during a 60 minute period. After all feedings are complete and it is given ,: < or a period of 60 minutes at reflux, the reaction was cooled and filtered to give a solid mass of N-phosphonornetiiirninodiacetic acid. The resulting filtrate was fortified with another 266 g of indole diacetic acid and PCI3 and formalin were fed in the manner and in the amount indicated above. After all the feeds were completed, and a reflux time of 60 minutes was allowed, the reaction was cooled and filtered. The combined cake mass of the two reactions amounted to 678 g and N-osphonomethoxide was 98% by weight, 98% by weight. The mother liquors above contained 123 g of N-phosphonornethyl nitric acid and 34 g of nitrous oxide acid.

This is a yield of 94% of N-fos fonomet iiinino-5 diacetic acid, based on the unrecovered idiodacetic acid. In that way, the process of the present invention, as illustrated in Examples 1-4, gave high yields of 93% to 97%, using the single-step process of the present invention. Lf) In view of the above-, it can be seen that the various advantages of the invention are achieved and other advantageous results are achieved. Since several changes can be made to the above methods and compositions without departing from the scope of the invention, it is intended that the material contained in the preceding description be interpreted as illustrative and not in a limiting sense.

Claims (18)

NOVELTY OF THE INVENTION CLAIMS

1. - A process for preparing N-phosphonomethyl-1,3-diacetic acid, characterized in that it comprises combining in a reaction mixture and water, a source of ammoniacet LCO acid, a source of fnalnaldehyde, a source of phosphorous acid and a source of a strong acid; wherein the source of phosphorous acid and the source of phosphorous acid are simultaneously in the reaction mixture to form the acid N-phosphonomethylnodiacetyl.

2. A process according to claim 1, further characterized by simultaneously infusing the water, the source of nninodiacetic acid, the source of formaldehyde, the source of phosphoric acid and the source of strong acid.

3. A method according to claim 1, further characterized in that the monoamyoacetic acid source is selected from the group consisting of ia modiacetic acid, a strong mineral acid salt of iammodiacetic acid, an alkali metal salt of imino-dithic acid and its combinations.

4. A process according to claim 3, further characterized in that the source of imamodiacetic acid is the rnonosodium salt of IDA. > - >

5. - A process according to claim 1, further characterized in that the source of acid irru nodi cet i co is the disodium salt of TOA.

6. A procedure according to claim 3, also characterized in that the formal source of the group consisting of gaseous formaldehyde, an aqueous solution of formaldehyde and formaldehyde is selected. r

7. - A method according to claim b, characterized in that the source of formaldehyde is an aqueous solution of formal due.

8. A process according to claim 3, further characterized in that the source of phosphorous acid is selected from the group consisting of phosphorous acid and a phosphorus halide.

9. A method according to claim 8, further characterized in that the source of phosphorous acid is phosphorus trichloride.

10. A process according to claim 3, further characterized in that the source of strong acid is selected from the group. which consists of a strong acid and a phosphorus halide.

11. A process according to claim 10, further characterized in that the source of strong acid is phosphorus trichloride.

12. A process according to claim 3, further characterized in that the process comprises adi citonally continuously remove the acid N-tos fonomet i Lirní nodiacot co of the reaction mixture. 13.- A p? ocodimient? of confo mity with claim 2, further characterized by the infusion of the source of irninodiacetic acid, the source of aldehyde, the source of phosphorous acid and the source of strong acid, substantially at the same rate. 14. - A p? or according to claim 1, further characterized in that before infusing the method it comprises additionally adding a source of IDA. 15. A process according to claim 1, further characterized in that before infusing, the process further comprises adding a strong acid and / or a source of phosphorous acid and strong acid. 16. A process according to claim 1, further characterized in that the reaction mixture is maintained under a pressure that increases above the ambient pressure. 17. A method according to claim 16, further characterized in that the pressure is from 1.05 to 2.10 kg / cm2 crn. 18. A process according to claim 1, further characterized in that the reaction mixture is maintained at a temperature above room temperature. 19 .- A method according to claim 18, further characterized in that the temperature is 105 ° C to around 145 ° C.