Method for the synthesis of N-phosphonomethyliminodiacetic acid

Abstract

A method for synthesis of N-phosphonoalkyliminodiacetic acid or derivatives thereof by forming a reaction mixture having an acid catalyst, a compound of the following general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 and a compound having one or more POP anhydride moieties to form a compound having a formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3R.sup.3.sub.2)(CH.sub.2R.sup.2) wherein in R.sup.1CH.sub.2NXCH.sub.2R.sup.2: X is CH.sub.2OH or CH.sub.2COOH; R.sup.1 and R.sup.2 are independently selected from the group consisting of nitrile, C.sub.1-C.sub.4 alkyl carboxylate, and carboxylic acid for when X is CH.sub.2OH, or R.sup.1 and R.sup.2 are both carbonyl groups linked by a hydrogen substituted nitrogen atom or a C.sub.1-C.sub.4-alkyl substituted nitrogen atom; and R.sup.3 is H, an alkyl group, or an aryl group; the anhydride moieties in the POP anhydride compound have one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V); and 2) hydrolyzing the mixture to form N-phosphonomethyliminodiacetic acid or one of its derivatives.

Claims

1. A method for synthesis of N-phosphonomethyliminodiacetic acid or derivatives thereof selected from the group consisting of phosphonate esters of N-phosphonomethyliminodiacetic acid, carboxylate esters of N-phosphonomethyliminodiacetic acid, phosphonate and carboxylate esters of N-phosphonomethyliminodiacetic acid, N-phosphonomethyliminodiacetic acid salts, phosphonate esters of N-phosphonomethyliminodiacetic acid salts, carboxylate esters of N-phosphonomethyliminodiacetic acid salts and phosphonate-carboxylate esters of N-phosphonomethyliminodiacetic acid salts, wherein a cation of the salt is selected from the group consisting of ammonium, isopropylammonium, ethanolammonium, dimethylammonium, trimethylsulfonium, sodium and potassium, comprising the steps of: a) forming an anhydrous reaction mixture comprising an acid catalyst, a compound of the following general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 and a compound having one or more POP anhydride moieties, to form a compound having the general formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3R.sup.3.sub.2)(CH.sub.2R.sup.2), wherein in the compound of the formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2: X is CH.sub.2COOH and R.sup.1 and R.sup.2 are each independently nitrile or C.sub.1-C.sub.4 alkyl carboxylate, or R.sup.1 and R.sup.2 are both carbonyl groups linked by means of a hydrogen substituted nitrogen atom or a C.sub.1-C.sub.4-alkyl substituted nitrogen atom; or X is CH.sub.2OH and R.sub.1 and R.sub.2 are each independently nitrile, C.sub.1-C.sub.4 carboxylate, or carboxylic acid, or R.sup.1 and R.sup.2 are both carbonyl groups linked by means of a hydrogen substituted nitrogen atom or a C.sub.1-C.sub.4-alkyl substituted nitrogen atom; and wherein in the compound having the general formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3R.sup.3.sub.2)(CH.sub.2R.sup.2), R.sup.3 is H, an alkyl group; and the POP anhydride moieties comprising compound is a compound wherein at least one of the one or more POP anhydride moieties comprises one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V) and is selected from the group consisting of tetraphosphorus hexaoxide, P.sub.4O.sub.7, P.sub.4O.sub.8, P.sub.4O.sub.9, pyrophosphites of general formula (RO).sub.2POP(OR).sub.2 wherein R is an alkyl or aryl group, and combinations thereof, and b) hydrolyzing the compound having the general formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3R.sup.3.sub.2)(CH.sub.2R.sup.2) to form N-phosphonomethyliminodiacetic acid or one of its derivatives.

2. The method of claim 1 wherein the R.sup.1CH.sub.2NXCH.sub.2R.sup.2 compound is a 4-X-piperazine-2,6-dione or a 4-X-1-(C.sub.1-C.sub.4 alkyl)piperazine-2,6-dione.

3. The method of claim 1, wherein ratio of NX moieties to POP anhydride moieties is between 0.3 and 2.0.

4. The method of claim 1, wherein the compound of the general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 is selected from the group consisting of N-hydroxymethyliminodiacetonitrile, N-hydroxymethyliminodiacetic acid, N-hydroxymethyliminodiacetic acid dimethylester, N-hydroxymethyliminodiacetic acid diethylester, N-carboxymethyliminodiacetonitrile, N-carboxymethyliminodiacetic acid dimethylester and N-carboxymethyliminodiacetic acid diethylester.

5. The method of claim 1, wherein the compound comprising the POP anhydride moieties is selected from the group consisting of tetraphosphorus hexaoxide, P.sub.4O.sub.7, P.sub.4O.sub.8, P.sub.4O.sub.9, tetraethylpyrophosphite, and combinations thereof.

6. The method of claim 1, wherein the compound comprising the POP anhydride moieties is tetraphosphorus hexaoxide.

7. The method of claim 1, wherein the acid catalyst is a homogeneous Brnsted acid catalyst selected from the group consisting of methanesulfonic acid, trifluoromethanesulfonic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, phosphorous acid, phosphoric acid and mixtures thereof.

8. The method of claim 1, wherein the acid catalyst is a heterogeneous Brnsted acid selected from the group consisting of: (i) supported or unsupported solid acidic metal oxides; (ii) cation exchange resins selected from the group consisting of copolymers of styrene, ethylvinyl benzene and divinyl benzene, functionalized so as to graft SO.sub.3H moieties onto an aromatic group and perfluorinated resins carrying carboxylic and/or sulfonic acid groups; (iii) organic sulfonic, carboxylic and phosphonic Brnsted acids, wherein the Brnsted acids are substantially immiscible in the reaction mixture at a reaction temperature; (iv) an acid catalyst derived from: interaction of a solid support having a lone pair of electrons onto which is deposited an organic Brnsted acid; interaction of a solid support having a lone pair of electrons onto which is deposited a compound having a Lewis acid site; or heterogeneous solids functionalized by chemical grafting with a Brnsted acid group or a precursor thereof; and (v) heterogeneous heteropolyacids of the general formula H.sub.xPM.sub.yO.sub.z wherein P is selected from phosphorus and silicon and M is selected from tungsten and molybdenum and combinations thereof.

9. The method of claim 1, wherein the acid catalyst is a homogeneous Lewis acid selected from the group consisting of LiN(CF.sub.3SO.sub.2).sub.2, Mg(OCF.sub.3SO.sub.2).sub.2, Al(OCF.sub.3SO.sub.2).sub.3, Bi(OCF.sub.3SO.sub.2).sub.3, and Sc(OCF.sub.3SO.sub.2).sub.3.

10. The method of claim 1, wherein the acid catalyst is a heterogeneous Lewis acid obtained from interaction of a homogeneous Lewis acid catalyst and an organic or inorganic polymer compound.

11. The method of claim 1, wherein step a) is carried out in the presence of a solvent selected from the group consisting of 1,4-dioxane, toluene, ethyl acetate, acetonitrile, sulfolane, 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl) imide, and mixtures thereof.

12. The method of claim 1, wherein the POP anhydride moiety comprising compound is gradually added to the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 while maintaining a temperature of step a) below 100 C.

13. The method of claim 1, wherein the POP anhydride moiety comprising compound is gradually added in step a) and wherein after completion of addition of the POP anhydride moiety comprising compound, step a) is heated to a temperature between 20 C. and 100 C. and maintained at the temperature for a period of time between 1 hour and 24 hours.

14. The method of claim 1, wherein the hydrolysis of step b) is performed at a temperature between 20 C. and 120 C., for a period between 10 minutes and 24 hours.

15. The method of claim 1, wherein the hydrolysis of step b) is performed under alkali conditions.

16. The method of claim 1, wherein the POP anhydride moiety comprising compound is selected from the group consisting of tetraphosphorus hexaoxide, P.sub.4O.sub.7, P.sub.4O.sub.8, P.sub.4O.sub.9, and combinations thereof.

17. The method of claim 1, further comprising converting the N-phosphonomethyliminodiacetic acid or a derivative thereof to N-(phosphonomethyl)glycine.

18. The method of claim 1, wherein the compound of the following general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 is N-hydroxymethyliminodiacetic acid.

19. The method of claim 18, wherein the POP anhydride moiety comprising compound is selected from the group consisting of tetraphosphorus hexaoxide, P.sub.4O.sub.7, P.sub.4O.sub.8, P.sub.4O.sub.9, and combinations thereof.

20. The method of claim 19, wherein the POP anhydride moiety comprising compound is tetraphosphorus hexaoxide.

21. The method of claim 18, further comprising converting the N-phosphonomethyliminodiacetic acid or a derivative thereof to N-(phosphonomethyl)glycine.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The present invention provides an efficient, economical and environmental friendly method for the synthesis of N-phosphonomethyliminodiacetic acid or its derivatives.

(2) Under derivatives the present invention understands salts, phosphonate and carboxylate esters of N-phosphonomethyliminodiacetic acid.

(3) The phosphonate and carboxylate esters comprise one or more substituted or unsubstituted hydrocarbyl groups which may be branched or unbranched, saturated or unsaturated and may contain one or more rings. Suitable hydrocarbyls include alkyl, alkenyl, alkynyl and aryl moieties. They also include alkyl, alkenyl, alkynyl and aryl moieties substituted with other aliphatic or cyclic hydrocarbyl groups, such as alkaryl, alkenaryl and alkynaryl.

(4) The substituted hydrocarbyl is defined as a hydrocarbyl wherein at least one hydrogen atom has been substituted with an atom other than hydrogen such as a halogen atom, an oxygen atom to form for example an ether or an ester group, a nitrogen atom to form an amide or a nitrile group or a sulfur atom to form for example a thioether group.

(5) The derivatives of N-phosphonomethyliminodiacetic acid preferably are obtained as such as an outcome of step a) or step b) or can be obtained by further treatment of N-phosphonomethyliminodiacetic acid. Under derivatives the present invention understands salts, phosphonate esters, carboxylate esters, phosphonate ester salts, carboxylate ester salts or phosphonate-carboxylate ester salts of N-phosphonomethyliminodiacetic acid. In the present invention it is understood that the expression N-phosphonomethyliminodiacetic acid comprises all derivatives.

(6) The method of the present invention includes the steps of:

(7) a) reacting, in the presence of an acid catalyst, a compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 with a POP anhydride moiety comprising compound to form a compound having the general formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3H.sub.2)(CH.sub.2R.sup.2), its dehydrated forms or their derivatives, wherein

(8) the compound of the formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 is characterized in that:

(9) X is CH.sub.2OH or CH.sub.2COOH and

(10) R.sup.1 and R.sup.2 are independently selected from the group consisting of nitrile, C.sub.1-C.sub.4 alkyl carboxylate, or R.sup.1 an R.sup.2 are both carbonyl groups linked by means of a hydrogen substituted nitrogen atom or a C.sub.1-C.sub.4-alkyl substituted nitrogen atom, the R.sup.1CH.sub.2NXCH.sub.2R.sup.2 formula thus corresponding to 4-X-piperazine-2,6-dione or 4-X-1-(C.sub.1-C.sub.4 alkyl)piperazine-2,6-dione, and wherein

(11) the said POP anhydride comprising compound is characterized in that said anhydride moieties comprise one P atom at the oxidation state (+III) and one P-atom at the oxidation state (+III) or (+V); and

(12) b) hydrolyzing the said compound having the general formula R.sup.1CH.sub.2N(CH.sub.2PO.sub.3H.sub.2)(CH.sub.2R.sup.2), its dehydrated forms or their derivatives to form N-phosphonomethyliminodiacetic acid or one of its derivatives.

(13) While the POP anhydride moiety comprising compound is preferably selected from the group consisting of tetraphosphorus hexaoxide and partially hydrolyzed species of tetraphosphorus hexaoxide obtained through reaction of 1 mole of tetraphosphorus hexaoxide with 1, 2, 3, 4 or 5 moles of water respectively, it is understood that all compounds comprising at least one POP anhydride group wherein one P-atom is at the oxidation state (+III) and the other P-atom is at the oxidation state (+III) or (+V) can be used for the purpose of the present invention.

(14) Suitable POP anhydride moiety comprising compounds can either comprise a POP anhydride moiety in the compound itself (e.g. P.sub.4O.sub.6 or pyrophosphites (RO).sub.2POP(OR).sub.2) or can be generated in situ by combining reagents that will form the required POP anhydride moiety upon combination before reacting with the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2.

(15) Suitable reagent combinations are:

(16) a) compounds containing a least one POH moiety (also accessible by tautomerization of a >P(O)H moiety into >P(LP)OH (where LP stands for lone pair of electrons) such as for example is the case for dimethylphosphite (MeO).sub.2P(O)H) and compounds containing at least one POP anhydride moiety e.g. P.sub.2O.sub.5 or P.sub.4O.sub.6;
b) compounds containing at least one POH moiety and compounds containing at least one PX (X=Cl, I, Br) moiety;
c) compounds containing at least one PX moiety and H.sub.2O;
d) compounds containing POP anhydride moieties and H.sub.2O for partial hydrolysis.

(17) In case a) and b) it is mandatory that at least in one of the utilized compounds the P-atom is in the oxidation state (+III) whereas in case c) each P-atom has to be in the oxidation state (+III) and in case d) the POP anhydride moieties have one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V), in order to form the POP anhydride moiety comprising compound, having one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V).

(18) The POP anhydride moiety comprising compounds wherein the POP anhydride moiety is already present are phosphorus oxides with the formula P.sub.4O.sub.n with n=6-9, pyrophosphites with the general formula (RO).sub.2POP(OR).sub.2 wherein R is an alkyl or aryl group, pyrophosphorous acid (H.sub.4P.sub.2O.sub.5) and isohypophosphoric acid (H)(HO)P(O)OP(O)(OH).sub.2.

(19) Combinations described under a) are obtained by reacting e.g. phosphorus oxides with formula P.sub.4O.sub.n with n=6-10, alkyl substituted pyrophosphites, pyrophosphorous acid, isohypophosphoric acid, metaphosphoric acid or polyphosphoric acid with phosphorous acid, phosphoric acid, mono or disubstituted phosphites with formula (RO)PO.sub.2H.sub.2 or (RO).sub.2POH wherein R is an alkyl or aryl group, phosphate esters (RO)PO.sub.3H.sub.2 or (RO).sub.2PO.sub.2H, phosphonic acids RPO.sub.3H.sub.2 or its monoester RPO.sub.2H(OR) with the proviso that such combinations will lead to POP anhydride moiety comprising compounds having one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V).

(20) Combinations described under b) are obtained by combining PCl.sub.3, PBr.sub.3, POCl.sub.3, mono or dichloro phosphites like (RO).sub.2PCl and (RO)PCl.sub.2 with phosphorous acid, phosphoric acid, mono or disubstituted phosphites with formula (RO)PO.sub.2H.sub.2 or (RO).sub.2POH with the proviso that such combinations will lead to POP anhydride moiety comprising compounds having one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V).

(21) Combinations described under c) are obtained by combining PCl.sub.3, PBr.sub.3, mono or dichloro phosphites like (RO).sub.2PCl and (RO)PCl.sub.2 with H.sub.2O. In order to obtain a POP anhydride moiety comprising compound free of PX functions the remaining PX functions are hydrolyzed with water. Remaining POP anhydride moieties can also be hydrolyzed as long as the required POP anhydride moiety wherein one P-atom is at the oxidation state (+III) and the other P-atom is at the oxidation state (+III) or (+V) remains.

(22) Most preferred species are tetraphosphorus hexaoxide, tetraethylpyrophosphite, and the combinations of phosphorous acid and tetraphosphorus hexaoxide, of phosphorous acid and tetraphosphorus decaoxide, of phosphorous acid and phosphorus trichloride, of dimethylphosphite and tetraphosphorus decaoxide, of phosphorus trichloride and water and of tetraphosphorus hexaoxide and water.

(23) The amount of reactive P(+III) atoms that can be converted into phosphonic acids according to this invention is determined by the amount of P(+III) atoms and the amount of POP anhydride moieties. If there are more POP anhydride moieties than P(+III) atoms, then all P(+III) atoms are converted into phosphonic acids. If there are less POP anhydride moieties than P(+III) atoms, then only a part of P(+III) atoms equal to the amount of POP anhydride moieties is converted into phosphonic acids.

(24) If halogen containing starting materials, e.g. PCl.sub.3, POCl.sub.3 or PBr.sub.3, are used, the level of halogen in the POP anhydride comprising compound shall be kept below 1000 ppm, usually below 500 ppm, preferably below 200 ppm, expressed in relation to the POP material being 100%. Therefore all excess PX functions are hydrolyzed before the reactions with the substrate by addition of one molecule of H.sub.2O per excess of PX function. The formed HX is removed by e.g. blowing a dry inert gas, like nitrogen or helium, through the solution.

(25) The tetraphosphorus hexaoxide preferably used within the scope of the present invention may be represented by a substantially pure compound containing at least 85%, preferably more than 90%, more preferably at least 95% and in one particular execution at least 97% of P.sub.4O.sub.6. While tetraphosphorus hexaoxide, suitable for use within the context of this invention, may be manufactured by any known technology, in preferred executions it is prepared in accordance with the method described in WO 2009/068636 and/or WO 2010/055056 patent applications under the section entitled Process for the manufacture of P.sub.4O.sub.6 with improved yield. In detail, oxygen, or a mixture of oxygen and inert gas, and gaseous or liquid phosphorus are reacted in essentially stoichiometric amounts in a reaction unit at a temperature in the range from about 1600 K to about 2000 K, by removing the heat created by the exothermic reaction of phosphorus and oxygen, while maintaining a preferred residence time of from about 0.5 seconds to about 60 seconds followed by quenching the reaction product at a temperature below 700 K and refining the crude reaction product by distillation. The tetraphosphorus hexaoxide so prepared is a pure product containing usually at least 97% of the oxide. The so produced P.sub.4O.sub.6 is generally represented by a liquid material of high purity containing in particular low levels of elementary phosphorus, P.sub.4, preferably below 1000 ppm, expressed in relation to the P.sub.4O.sub.6 being 100%. The preferred residence time is from 5 seconds to 30 seconds, more preferably from 8 seconds to 30 seconds. The reaction product can, in one preferred execution, be quenched to a temperature below 350 K.

(26) It is presumed that the P.sub.4O.sub.6 participating in a reaction at a temperature of from about 24 C. (melting t) to about 120 C. is necessarily liquid or gaseous although solid species can, academically speaking, be used in the preparation of the reaction medium.

(27) For reasons of convenience and operational expertise, the tetraphosphorus hexaoxide, represented by P.sub.4O.sub.6, is of high purity and contains very low levels of impurities, in particular elemental phosphorus, P.sub.4, at a level below 1000 ppm, usually below 500 ppm and preferably not more than 200 ppm, expressed in relation to the P.sub.4O.sub.6 being 100%.

(28) In the present invention it is understood that when using the terminology POP anhydride moiety comprising compound it is meant POP anhydride moiety comprising compound wherein one P atom is at the oxidation state (+III) and the other P atom is at the oxidation state (+III) or (+V).

(29) The compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 is characterized in that: X is CH.sub.2OH or CH.sub.2COOH R.sup.1 and R.sup.2 are independently selected from the group consisting of nitrile, C.sub.1-C.sub.4 alkyl carboxylate, or are both carbonyl groups linked by means of a hydrogen substituted nitrogen or a C.sub.1-C.sub.4-alkyl substituted nitrogen atom, the R.sup.1CH.sub.2NXCH.sub.2R.sup.2 formula thus corresponding to 4-X-piperazine-2,6-dione or 4-X-1-(C.sub.1-C.sub.4 alkyl)piperazine-2,6-dione.

(30) The compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 is preferably selected from the group consisting of N-hydroxymethyliminodiacetonitrile, N-hydroxymethyliminodiacetic acid, N-hydroxymethyliminodiacetic acid dimethyl ester, N-hydroxymethyliminodiacetic acid diethylester, N-hydroxymethyliminodiacetic acid dipropylester, N-hydroxymethyliminodiacetic acid diisopropylester, N-hydroxymethyliminodiacetic acid di-butylester, N-hydroxymethyliminodiacetic acid di-isobutylester, N-hydroxymethyliminodiacetic acid di-sec-butylester, N-hydroxymethyliminodiacetic acid di-tert-butylester, 4-hydroxymethylpiperazine-2,6-dione, 4-hydroxymethyl-1-methylpiperazine-2,6-dione, 4-hydroxymethyl-1-ethylpiperazine-2,6-dione, 4-hydroxymethyl-1-propylpiperazine-2,6-dione, 4-hydroxymethyl-1-isopropylpiperazine-2,6-dione, 4-hydroxymethyl-1-butylpiperazine-2,6-dione, 4-hydroxymethyl-1-isobutylpiperazine-2,6-dione, 4-hydroxymethyl-1-sec-butylpiperazine-2,6-dione, 4-hydroxymethyl-1-tert-butylpiperazine-2,6-dione, N-carboxymethyliminodiacetonitrile, N-carboxymethyliminodiacetic acid dimethylester, N-carboxymethyliminodiacetic acid diethylester, N-carboxymethyliminodiacetic acid dipropylester, N-carboxymethyliminodiacetic acid diisopropylester, N-carboxymethyliminodiacetic acid di-butylester, N-carboxymethyliminodiacetic acid di-isobutylester, N-carboxymethyliminodiacetic acid di-sec-butylester, N-carboxymethyliminodiacetic acid di-tert-butylester, 4-carboxymethylpiperazine-2,6-dione, 4-carboxymethyl-1-methylpiperazine-2,6-dione, 4-carboxymethyl-1-ethylpiperazine-2,6-dione, 4-carboxymethyl-1-propylpiperazine-2,6-dione, 4-carboxymethyl-1-isopropylpiperazine-2,6-dione, 4-carboxymethyl-1-butylpiperazine-2,6-dione, 4-carboxymethyl-1-isobutylpiperazine-2,6-dione, 4-carboxymethyl-1-sec-butylpiperazine-2,6-dione and 4-carboxymethyl-1-tert-butylpiperazine-2,6-dione.

(31) The compound having the general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 wherein X is CH.sub.2OH may be prepared by reacting R.sup.1CH.sub.2NHCH.sub.2R.sup.2 and formaldehyde in the presence of an acid catalyst and optionally a solvent.

(32) The compound having the general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 wherein X is CH.sub.2COOH may be prepared by reacting R.sup.1CH.sub.2NHCH.sub.2R.sup.2 and chloroacetic acid in an alkaline medium.

(33) The acid catalyst preferably used within the scope of the present invention is a homogeneous Brnsted acid catalyst, optionally in the presence of a solvent, or a heterogeneous Brnsted acid catalyst, in the presence of a solvent, or a Lewis acid catalyst, in the presence of a solvent.

(34) The homogeneous Brnsted acid is preferably selected from the group consisting of methanesulfonic acid, fluoromethanesulfonic acid, trichloromethanesulfonic acid, trifluoromethanesulfonic acid, acetic acid, trifluoroacetic acid, tert-butyl-sulfonic acid, p-toluenesulfonic acid, naphthalene sulfonic acid, 2,4,6-trimethylbenzene-sulfonic acid, perfluoro or perchloro alkyl sulfonic acids, perfluoro or perchloro alkyl carboxylic acids, hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphorous acid and phosphoric acid, and mixtures thereof. The homogeneous Brnsted acid is preferably methanesulfonic acid.

(35) The heterogeneous Brnsted acid is preferably selected from the group consisting of:

(36) (i) solid acidic metal oxide combinations as such or supported onto a carrier material;

(37) (ii) cation exchange resins selected from the group comprising copolymers of styrene, ethylvinyl benzene and divinyl benzene, functionalized so as to graft SO.sub.3H moieties onto the aromatic group and perfluorinated resins carrying carboxylic and/or sulfonic acid groups;

(38) (iii) organic sulfonic, carboxylic and phosphonic Brnsted acids which are substantially immiscible in the reaction medium at the reaction temperature;

(39) (iv) an acid catalyst derived from: the interaction of a solid support having a lone pair of electrons onto which is deposited an organic Brnsted acid; or the interaction of a solid support having a lone pair of electrons onto which is deposited a compound having a Lewis acid site; or heterogeneous solids functionalized by chemical grafting with a Brnsted acid group or a precursor therefore; and

(40) (v) heterogeneous heteropolyacids of the general formula H.sub.xPM.sub.yO.sub.z wherein P is selected from phosphorus and silicon and M is selected from tungsten and molybdenum and combinations thereof.

(41) Preferred homogeneous Lewis acids can be selected from metal salts having the general formula MX.sub.n,

(42) wherein M represents a main group element or transition metal like Li, B, Mg, Al, Bi, Fe, Zn, La, Sc, Yb, or Pd; X in MX.sub.n is typically an anion of an acid or acid derivative like Cl, OTf or NTf.sub.2, where Tf stands for CF.sub.3SO.sub.2.sup. and n is equal to the oxidation state of M, which can be from 1 to 5. Possible combinations are e.g. LiNTf.sub.2, Mg(OTf).sub.2, MgCl.sub.2, ZnCl.sub.2, PdCl.sub.2, Fe(OTf).sub.3, Al(OTf).sub.3, AlCl.sub.3, Bi(OTf).sub.3, BiCl.sub.3, Sc(OTf).sub.3, Ln(OTf).sub.3, Yb(OTf).sub.3. Preferably, combinations of a hard metal or a metal on the borderline between hard and soft according to the HSAB (hard soft acid base) concept like Li, Mg, Al, Sc, Zn, Bi, and weekly coordinating anions like OTf or NTf.sub.2 are used. Examples of such preferred combinations are: LiNTf.sub.2, Mg(OTf).sub.2, Al(OTf).sub.3, Bi(OTf).sub.3.

(43) Preferred heterogeneous Lewis acids can be represented by species of discretionary selected subclasses created by interaction/bonding of homogeneous Lewis acids e.g. metal complexes, metal salts or organometallic species with polymeric organic or inorganic backbones. An example of such subclass is a polystyrene matrix with bonded Sc(OTf).sub.2 groups. Such catalyst can be prepared e.g. by interaction of a polystyrene sulfonic acid resin, e.g. Amberlyst 15, with Sc(OTf).sub.3. The number of equivalents of Lewis acid functions can be determined in this case by different ways e.g. by acid base determination of the unreacted sulfonic acid groups, by quantitative determination of the liberated triflic acid and by ICP measurement of the amount of Sc on the resin.

(44) Typical examples of suitable solvents, optionally used in the method according to the present invention, are anisole; chlorinated and fluorinated hydrocarbons such as fluorobenzene, chlorobenzene, tetrachloroethane, tetrachloroethylene, dichloroethane, dichloromethane; polar solvents like diglyme, glyme, diphenyloxide, polyalkylene glycol derivatives with capped OH groups such as OR*** where R*** is a low alkyl or acyl group, aliphatic hydrocarbons such as hexane, heptane, cyclohexane; non-cyclic ethers like dibutyl ether, diethyl ether, diisopropyl ether, dipentylether, and butylmethylether cyclic ethers like tetrahydrofuran, dioxane, and tetrahydropyran; mixed cyclic/non-cyclic ethers like cyclopentylmethylether; cyclic and non-cyclic sulfones like sulfolane, aromatic solvents like toluene, benzene, xylene; organic acetates like ethylacetate; organic nitriles like acetonitrile, benzonitrile; silicon fluids like polymethylphenyl siloxane or mixtures thereof; non-reactive ionic liquids like 1-n-butyl-imidazolium trifluoromethanesulfonate, and 1-ethyl-3-methyl-imidazolium bis(trifluoromethyl sulfonyl)imide or a mixture thereof.

(45) In a particular embodiment of the present invention the acid catalyst acts as catalyst and as solvent.

(46) In step a) of the process of the present invention, the POP anhydride moiety comprising compound and the compound with general formula

(47) R.sup.1CH.sub.2NXCH.sub.2R.sup.2 are gradually mixed at a temperature of about 100 C. or less.

(48) With the terminology gradually mixed the present invention understands:

(49) the gradual addition of the POP anhydride moiety comprising compound to the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2, the gradual addition of the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 to the POP anhydride moiety comprising compound, the simultaneous gradual addition of the POP anhydride moiety comprising compound and the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 each at independent rate into a medium where reaction between both compounds may proceed.

(50) In general, the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, is gradually added to the compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 while the temperature is maintained at a value of about 100 C. or less and preferably at a temperature comprised between about 20 C. and about 70 C. Once the addition completed, step a) is maintained at a temperature comprised between about 20 C. and about 100 C., preferably between about 30 C. and about 90 C. for a period of time comprised between about 1 hour and about 24 hours.

(51) During the conversion of the compound with general formula

(52) R.sup.1CH.sub.2NXCH.sub.2R.sup.2, wherein X is CH.sub.2COOH, one equivalent of carbon monoxide will be formed for each converted CH.sub.2COOH equivalent. Carbon monoxide will leave the reaction mixture as a gas of very high purity. This carbon monoxide gas can be used in many applications like e.g. as a fuel, in combination with hydrogen for methanol and Fischer-Tropsch hydrocarbons manufacture, for hydroformylation reactions, for alcohol carbonylation e.g. carbonylation of methanol to acetic acid or the conversion of methyl acetate to acetic anhydride.

(53) After completion of the conversion of R.sup.1CH.sub.2NXCH.sub.2R.sup.2 into

(54) R.sup.1CH.sub.2N(CH.sub.2PO.sub.3H.sub.2)(CH.sub.2R.sup.2) in step a), water is optionally added in step b) in order to hydrolyze unreacted POP anhydride moieties, if present, and to convert, N-phosphonomethyliminodiacetonitrile, N-phosphonomethyliminodiacetic acid di-(C.sub.1-C.sub.4)alkylester, 4-phosphonomethyl-piperazine-2,6-dione or 4-phosphonomethyl-1-(C.sub.1-C.sub.4 alkyl)piperazine-2,6-dione into N-phosphonomethyliminodicarboxylic acid.

(55) Unreacted POP anhydride moieties may be the result of an incomplete conversion or of an out of stoichiometric amount of POP anhydride group comprising compounds, i.e. an excess of POP anhydride moieties relative to the NX equivalents.

(56) Preferably, water is added after completion of step a) and after step a) is cooled down to room temperature. Alternatively step a), after being completed, can be cooled down through the addition of the water. This hydrolysis is performed at a temperature comprised between about 20 C. and about 100 C., preferably between about 40 C. and about 100 C., for a period comprised between about 10 minutes and about 24 hours and preferably between about 1 hour and about 10 hours.

(57) When the hydrolysis is performed under alkali conditions the alkali aqueous solution used is preferably obtained from a base selected from the group consisting of alkali hydroxides, alkaline earth hydroxides, ammonia and primary aliphatic amines; preferably said base is sodium hydroxide or potassium hydroxide.

(58) When the hydrolysis is performed under acid conditions the acid aqueous solution used is preferably obtained from a mineral acid; preferably said mineral acid is volatile and most preferable this acid is hydrochloric acid.

(59) The N-phosphonomethyliminodiacetic acid may be recovered from step b) through precipitation. Precipitation can be facilitated by the cooling of step b). Numerous well known methods, such as for example filtration, can be used to recover the precipitate.

(60) The method of the present invention can be utilized in any reactor system known in the art including batch reactors, continuous reactors or semi-continuous reactors.

EXAMPLES

(61) The following examples illustrate the invention; they are merely meant to exemplify the present invention, but are not destined to limit or otherwise define the scope of the present invention.

Example 1

(62) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser 1.53 g (10.0 mmole) N,N-biscyanomethyl glycine and 2.0 g (10.0 mmole of H.sup.+) Amberlyst 15 were mixed with 5 ml acetonitrile and heated to 60 C. Slowly, 0.55 g (2.5 mmole) P.sub.4O.sub.6 was added. The reaction mixture was heated for 3 hours at 60 C. During the addition and reaction time the evolution of CO was observed. 2 ml H.sub.2O was added and afterwards the pH was brought to above 10 by addition of a NaOH solution. The obtained solution was heated for 24 hours at 60 C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-Phosphonomethyliminodiacetic acid was detected at 80.5% by weight. The ratio of mmoles N,N-biscyanomethyl glycine to mmoles P.sub.4O.sub.6 equals 4.0; the ratio of milliequivalents Amberlyst 15 to mmoles N,N-biscyanomethyl glycine equals 1.0; the ratio of milliequivalents Amberlyst 15 to mmoles P.sub.4O.sub.6 equals 4.0.

(63) In table 1 a series of examples (Example 2 to 12), according to the present invention, is reported.

(64) In this table:

(65) Column 1: indicates the identification number of the example. Column 2: indicates the type of compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 Column 3: indicates the number of mmoles of compound with general formula R.sup.1CH.sub.2NXCH.sub.2R.sup.2 Column 4: indicates the type of catalyst and solvent if present. Column 5: indicates the number of mmoles of catalyst. Column 6: indicates the number of mmoles of tetraphosphorus hexaoxide. Column 7: indicates the ratio of mmoles of R.sup.1CH.sub.2NXCH.sub.2R.sup.2 compound to mmoles of tetraphosphorus hexaoxide Column 8: indicates the ratio of mmoles of catalyst to mmoles of R.sup.1CH.sub.2NXCH.sub.2R.sup.2 compound. Column 9: indicates the ratio of mmoles catalyst to mmoles of tetraphosphorus hexaoxide. Column 10: indicates the temperature ( C.) for the gradually mixing the constituents of step a). Column 11: indicates the temperature ( C.) and time (hrs) conditions for completion of step a). Column 12: indicates the temperature ( C.) and time (hrs) conditions for completion of step b). Column 13: indicates the reaction yield, in % by weight, as measured by .sup.1H-NMR and .sup.31P-NMR spectroscopy.

Example 13

(66) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser 10.64 g (80.0 mmole) iminodiacetic acid and 2.40 g (26.7 mmole) 1,3,5-trioxane were mixed with 50 ml acetic acid and heated to 100 C. for 6 hours to form a reaction mixture comprising N-hydroxymethyliminodiacetic acid. After cooling to ambient temperature 4.40 g (20.0 mmole) P.sub.4O.sub.6 was added slowly. Then the reaction mixture was heated for 5 hours at to 50 C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-Phosphonomethyliminodiacetic acid was detected at 19.8% by weight.

Example 14

(67) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser 7.76 g (80.0 mmole) iminodiacetonitrile and 2.40 g (26.7 mmole) 1,3,5-trioxane were mixed with 50 ml acetic acid and heated to 80 C. for 5 hours. After cooling to ambient temperature 4.40 g (20.0 mmole) P.sub.4O.sub.6 was added slowly. Then the reaction mixture was heated for 6 hours at to 80 C. 10 ml H.sub.2O was added and the mixture was heated for 6 hours to 100 C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-Phosphonomethylimino diacetic acid was detected at 18.6% by weight.

Example 15

(68) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser 15.14 g (80.0 mmole) diethyl iminodiacetic acid and 2.40 g (26.7 mmole) 1,3,5-trioxane were mixed with 50 ml acetic acid and heated to 80 C. for 6 hours. After cooling to ambient temperature 4.40 g (20.0 mmol) P.sub.4O.sub.6 was added slowly. Then the reaction mixture was heated for 8 hours at to 80 C. 10 ml H.sub.2O was added and the mixture was heated for 6 hours to 100 C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-Phosphonomethylimino diacetic acid was detected at 53.0% by weight.

Example 16

(69) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 1.30 g (8 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13, was mixed with 5 ml (78 mmole) methanesulfonic acid. Slowly, 4.20 g (16 mmole) tetraethylpyrophosphite was added. Afterwards the reaction mixture was heated to 60 C. for 8 hours. Then 5 ml water was added and the mixture was stirred at 85 C. for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 52.1%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

Example 17

(70) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 6 ml of methanesulfonic acid, 0.97 g (8.8 mmole) of dimethylphosphite and 0.85 g (6 mmole) of P.sub.2O.sub.5 were mixed for 20 minutes at 85 C. Then 1.63 g (10 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13, was added and the reaction mixture was heated to 85 C. overnight. Then 5 ml of water was added and the mixture was stirred at 85 C. for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 42.5%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

Example 18

(71) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 6 ml (92.4 mmole) of methanesulfonic acid, 1.8 g (22 mmole) of phosphorous acid and 0.3 ml (2.6 mmole) of P.sub.4O.sub.6 were premixed for 20 min at 85 C. Then 1.63 g (10 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13, was added and the reaction mixture was heated to 85 C. overnight. Then 5 ml of water was added and the mixture was stirred at 85 C. for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 15.7%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

Example 19

(72) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 10 ml (154 mmole) methanesulfonic acid, 1.64 g (20 mmole) of phosphorous acid and 2.80 g (20 mmole) of P.sub.2O.sub.5 were mixed for 1 hour above 50 C. Then 1.63 g (10 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13, was added and the reaction mixture was heated to 85 C. overnight. Then 6 ml of water was added and the mixture was stirred at 85 C. for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 44.0%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

Example 20

(73) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 10 ml (154 mmole) methanesulfonic acid, 1.8 ml (22 mmole) of dimethylphosphite and 2.8 g (20 mmole) of P.sub.2O.sub.5 were mixed for 1 hour above 50 C. Then 1.63 g (10 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13, was added and the reaction mixture was heated to 85 C. overnight. Then 6 ml of water was added and the mixture was stirred at 85 C. for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 61.0%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

Example 21

(74) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser, 0.82 g (10 mmole) phosphorous acid was mixed with 5 ml (78 mmole) methanesulfonic acid. Slowly 1.37 g (10 mmole) PCl.sub.3 was added, followed by 1.63 g (10 mmole) N-hydroxymethyliminodiacetic acid, obtained as in example 13. Afterwards the reaction mixture was stirred for 6 hours at 60 C. At ambient temperature 0.5 ml water was added and the mixture was kept standing for 1 hour. The yield of N-phosphonomethyliminodiacetic acid was 39.7%, as determined by .sup.1H- and .sup.31P-NMR spectroscopy.

(75) TABLE-US-00001 TABLE 1 Cata P.sub.4O.sub.6 X Cata Cata T.sub.1/ T.sub.2/time T.sub.3/time Ex R.sub.1CH.sub.2NXCH.sub.2R.sup.2 (mmole) Catalyst/Solvent (mmole) (mmole) P.sub.40.sub.6 X P.sub.4O.sub.6 C. C./hrs C./hrs Yield 2 N,N-biscyanomethyl 65.4 Methanesulfonic acid 246 16.3 4.0 3.8 15.0 40 70/5 25 39.3 glycine 3 N,N-biscyanomethyl 65.4 Methanesulfonic acid 131 16.3 4.0 2.0 8.0 25 30/2 25 15.1 glycine Acetonitrile (50 ml) (1*) 4 N,N-biscyanomethyl 65.4 Trifluoromethanesulfonic 130 16.3 4.0 2.0 8.0 25 30/4 100/7 86.1 glycine acid Acetonitrile (50 ml) 5 N,N-biscyanomethyl 65.4 Methanesulfonic acid 196 16.3 4.0 3.0 12.0 25 40/5 90/7 97.3 glycine Acetonitrile (50 ml) 25/16 6 N,N-biscyanomethyl 20.0 Trifluoromethanesulfonic 10 5.0 4.0 0.5 2.0 30 30/3 13.4 glycine acid Acetonitrile (10 ml) (2*) 7 N,N-biscyanomethyl 10.0 Methanesulfonic acid 77 2.5 4.0 7.7 31.0 25 25/3 60/24 74.0 glycine (3*) 8 N,N-biscyanomethyl 10.0 Trifluoroacetic acid 65 2.5 4.0 6.5 26.0 50 50/3 60/24 74.8 glycine (4*) 9 N,N-biscyanomethyl 10.0 Aluminium triflate 0.25 2.5 4.0 0.03 0.1 60 60/3 60/24 75.7 glycine Acetonitrile (5 ml) (5*) 10 N-hydroxymethyl 80.0 Acetic acid 873 20.0 4.0 10.9 43.7 25 50/5 19.8 Iminodiacetic acid 11 N-hydroxymethyl 80.0 Acetic acid 873 20.0 4.0 10.9 43.7 25 80/6 100/6 18.6 Iminodiacetic acid 12 N-hydroxymethylimino 80.0 Acetic acid 873 20.0 4.0 10.9 43.7 25 80/8 100/6 53.0 diacetic acid diethylester (1*): the oil obtained after completion of the hydrolysis comprises 37.6% weight of N,N-biscyanomethylaminomethylphosphonic acid and 15.1% weight of N-phosphonomethyliminodiacetic. (2*): in the synthesis of Example 6, no hydrolysis step is performed; finally 65.3% weight of N-phosphonomethyliminodiacetonitrile and 13.4% weight of N-phosphonomethyliminodiacetic acid is formed. (3*) to (5*): for the hydrolysis, the pH is brought to a value above 10 through the addition of sodium hydroxide.