Method for the synthesis of aminoalkylenephosphonic acid

Abstract

A method for the synthesis of an aminoalkylenephosphonic acid or its phosphonate esters including the following steps: a) forming, in the presence of an aldehyde or ketone and an acid catalyst, a reaction mixture by mixing a compound having at least one HNR.sup.1R.sup.2 moiety or a salt thereof, with a compound having one or more POP anhydride moieties, the moieties having one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V), wherein the ratio of moles of aldehyde or ketone to NH moieties is 1 or more and wherein the ratio of NH moieties to POP anhydride moieties is 0.3 or more, and b) recovering the resulting aminoalkylenephosphonic acid having compound or its phosphonate esters.

Claims

1. A method for the synthesis of an aminoalkylenephosphonic acid or its phosphonate esters, comprising the following steps: a) forming, in the presence of an aldehyde or ketone and an acid catalyst, a reaction mixture by mixing a compound (a.1.) comprising at least one HNR.sup.1R.sup.2 moiety or a salt thereof, with a compound (a.2.) having one or more POP anhydride moieties, said moieties comprising one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V), wherein the ratio of moles of aldehyde or ketone to NH moieties is 1 or more and wherein the ratio of NH moieties to POP anhydride moieties is 0.3 or more, and wherein: the HNR.sup.1R.sup.2 moiety comprising compound (a.1.) is characterized in that: R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkenyl, C.sub.1-C.sub.6 acyl, optionally comprising one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur and optionally comprising one or more carbonyl moieties, wherein R.sup.1 and R.sup.2 may combine to form a 5-6 membered substituted or unsubstituted ring wherein NH is incorporated in said ring, and wherein: the compound (a.2.) comprising one or more POP anhydride moieties, with said moieties comprising one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V), 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; and b) recovering the resulting compound comprising aminoalkylene phosphonic acid or one of its phosponate esters.

2. The method according to claim 1, wherein the ratio of NH moieties to POP moieties is comprised between 0.3 and 2.0.

3. The method according to claim 1, wherein the reaction of step a) is performed at a temperature comprised between 20? C. and 120? C., for a period of time comprised between 30 minutes and 24 hours.

4. The method according to claim 1 comprising the additional steps of: adding water to the reaction mixture after completion of the conversion of the HNR.sup.1R.sup.2 moiety comprising compound into the aminoalkylenephosphonic acid comprising compound; bringing the reaction mixture comprising the added water, to a temperature comprised between 20? C. and 150? C. and maintaining the reaction mixture comprising the added water at said temperature for at least 10 minutes.

5. The method according to claim 1, wherein the compound (a.2.) comprising the POP anhydride moiety is selected from the group consisting of tetraphosphorus hexaoxide, and tetraethylpyrophosphite.

6. The method according to claim 1, wherein the compound (a.2.) comprising the POP anhydride moieties is tetraphosphorus hexaoxide.

7. The method according to claim 1, wherein the aldehyde has the general formula RCOH and R is selected from the group consisting of hydrogen, aliphatic moiety, araliphatic moiety, aromatic moiety and heterocyclic moiety wherein the total number of carbon and hetero atoms is comprised between 1 and 11.

8. The method according to claim 1, wherein the ketone has the general formula RCOR and R and R are independently selected from the group consisting of aliphatic moiety, araliphatic moiety and aromatic hydrocarbon moiety wherein the total number of carbon atoms is comprised between 1 and 12.

9. The method according to claim 1, wherein the aldehyde is formaldehyde.

10. The method according to claim 1, wherein the acid catalyst is a homogeneous Br?nsted acid catalyst selected from the group consisting of methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, phosphorous acid, phosphoric acid and mixtures thereof.

11. The method according to claim 1, wherein the acid catalyst is a heterogeneous Br?nsted acid selected from the group consisting of: (i) solid acidic metal oxide combinations as such or supported by a carrier material; (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; (iii) organic sulfonic, carboxylic and phosphonic Br?nsted acids which are substantially immiscible in the reaction medium at the reaction temperature; (iv) an acid catalyst derived from: the interaction of a solid support having a lone pair of electrons onto which is deposited an organic Br?nsted acid; 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 Br?nsted acid group or a precursor therefore; 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.

12. The method according to 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.

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

14. The method according to claim 1, wherein the reaction mixture of step a) comprises a solvent selected from the group consisting of 1,4-dioxane, toluene, ethylacetate, acetonitrile, acetic acid, sulfolane, 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide, or a mixture thereof.

15. The method according to claim 1, which comprises the steps of: a) forming a reaction mixture by mixing a compound (a.1.) comprising at least one HNR.sup.1R.sup.2 moiety with an aldehyde or a ketone and an acid catalyst optionally in the presence of a solvent, to form a compound comprising at least one aminoalkylol moiety; b) adding a compound (a.2.) comprising at least one POP anhydride moiety, having one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V) to the reaction mixture of step a) comprising at least one aminoalkylol moiety, to form a compound comprising aminoalkylenephosphonic acid; c) adding water to the reaction mixture of step b); and d) recovering the resulting compound comprising aminoalkylenephosphonic acid or one of its phosphonate esters.

16. The method according to claim 1, wherein the hydrolysis, after completion of the formation of the compound comprising aminoalkylenephosphonic acid, is performed at a pH comprised between 4.0 and 7.0.

17. The method according to claim 1, wherein the hydrolysis, after completion of the formation of the compound comprising aminoalkylenephosphonic acid, is performed at a temperature comprised between 20? C. and 150? C. for a period comprised between 10 minutes and 72 hours.

18. The method according to claim 1, wherein the ratio of NH moieties to POP moieties is comprised between 0.5 and 1.5.

19. The method according to claim 3, wherein the reaction of step a) is performed for a period of time comprised between 1 hour and 20 hours.

20. The method according to claim 1, wherein the reaction of step a) is performed at a temperature comprised between 40? C. and 100? C., for a period of time comprised between 30 minutes and 24 hours.

21. The method according to claim 20, wherein the reaction of step a) is performed for a period of time comprised between 1 hour and 20 hours.

22. The method according to claim 17, wherein the hydrolysis, after completion of the formation of the compound comprising aminoalkylenephosphonic acid, is performed for a period comprised between 1 hour and 10 hours.

23. The method according to claim 1, wherein the hydrolysis, after completion of the formation of the compound comprising aminoalkylenephosphonic acid, is performed at a temperature comprised between 40? C. and 100? C., for a period comprised between 10 minutes and 72 hours.

24. The method according to claim 23, wherein the hydrolysis, after completion of the formation of the compound comprising aminoalkylenephosphonic acid, is performed for a period comprised between 1 hour and 10 hours.

25. The method according to claim 1, wherein the compound (a.1.) comprising at least one HNR.sup.1R.sup.2 moiety or a salt thereof is selected from the group consisting of N,N-bis(hydroxymethyl)ethylenediamine, N-hydroxymethylacetamide, N-(2-aminoethyl)ethane-1,2-diamine, N,N-bismethylolurea, glycine methyl ester, N-hydroxymethyl glycine methyl ester, ethylenediamine, morpholine, 2,5-oxazolidinedione, and combinations thereof.

26. The method according to claim 1, wherein the compound (a.2.) comprising the POP anhydride moiety is selected from the group consisting of tetraphosphorus hexaoxide, P.sub.4O.sub.7, P.sub.4O.sub.8, and P.sub.4O.sub.9.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The present invention provides an efficient and economical method for the synthesis of aminoalkylenephosphonic acid or its phosphonate esters with high selectivity and high yield.

(2) The phosphonate esters of the present invention 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.

(3) 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 an halogen atom (F, Cl, Br and I), an oxygen atom to form for example an ether or an ester, a nitrogen atom to form an amide or nitrile group or a sulfur atom to form for example a thioether group.

(4) Phosphonate esters in general are prepared by using the POP anhydride moiety comprising compound substituted with the corresponding hydrocarbyl substituents.

(5) The present method includes an arrangement whereby a compound comprising a POP anhydride moiety, having one P atom at the oxidation state (+III) and the other P atom at the oxidation state (+III) or (+V), ammonia, or a primary or secondary amine and an aldehyde or a ketone are reacted in the presence of an acid catalyst and optionally a solvent.

(6) While the POP anhydride moiety comprising compound is preferably selected from the group consisting of tetraphosphorus hexaoxide and partially hydrolysed species of tetraphosphorus hexaoxide obtained through reaction of 1 mole of tetraphosphorus hexaoxide with 1, 2, 3, 4 and 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.

(7) 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 aminoalkylol.

(8) Suitable reagent combinations are:

(9) a) compounds containing a least one POH moiety (also accessible by tautomerisation 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

(10) In case a) and b) it is mandatory that at least in one of the utilised compounds the P atom is in the oxidation state (+III) whereas in case c) the P atom has to be in the oxidation state (+III) and in case d) the POP 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).

(11) 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.

(12) 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.2Or 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).

(13) Combinations described under b) are obtained by combining PCl.sub.3, PBr.sub.3, POCl.sub.3 or mono or dichloro phosphites like (RO).sub.2PCl and (RO)PCl.sub.2 with phosphorous acid, phosphoric acid or 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).

(14) Combinations described under c) are obtained by combining PCl.sub.3, PBr.sub.3 or mono or dichloro phosphites like (RO).sub.2PCl and (RO)PCl.sub.2 with H.sub.2O.

(15) In order to obtain a POP anhydride moiety comprising compounds free of PX functions the remaining PX functions are hydrolysed. Remaining POP anhydride moieties can also be hydrolysed 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.

(16) Most preferred 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.

(17) 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.

(18) 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 hydrolysed, 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.

(19) 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 1600 K to 2000 K, by removing the heat created by the exothermic reaction of phosphorus and oxygen, while maintaining a preferred residence time of from 0.5 seconds to 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.

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

(21) 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%.

(22) 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)

(23) The HNR.sup.1R.sup.2-comprising compound, used in the present invention, can be a low molecular weight organic molecule or form part of a polymer wherein the low molecular weight organic molecule or the polymer may be grafted on inorganic material.

(24) For the HNR.sup.1R.sup.2 comprising compound being a low molecular weight organic molecule, it is further characterized in that:

(25) R.sup.1 and R.sup.2 are independently selected from hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkynyl, C.sub.1-C.sub.6 acyl, optionally comprising an ethylenically unsaturated double bond, and (meth)acryloyl C.sub.1-C.sub.6 moiety, wherein the C.sub.1-C.sub.6 part of said moieties is normal chained, branched or cyclised and is optionally substituted by one or more moieties selected from the group consisting of C.sub.1-C.sub.4 hydrocarbon, aryl and aralkyl and optionally comprises one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur and optionally comprises one or more carbonyl moieties.

(26) R.sup.1 and R.sup.2 may form a ring structure wherein NH is incorporated in said ring and wherein said ring is optionally substituted by one or more moieties selected from the group consisting of C.sub.1-C.sub.4 hydrocarbon, aryl and aralkyl and optionally comprises one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur and optionally comprises one or more carbonyl moieties.

(27) For the HNR.sup.1R.sup.2 comprising compound forming part of a polymer, at least one >NH is incorporated in the polymer chain or at least one NHR.sup.1 is a repeating substituent moiety on the polymer chain comprising polymerized R.sup.2 moieties, optionally copolymerized with other polymerizable monomers.

(28) The HNR.sup.1R.sup.2 comprising compound forming part of a polymer is further characterized in that R.sup.1 and R.sup.2 are independently selected from the group consisting of:

(29) hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkynyl, C.sub.1-C.sub.6 acyl comprising at least 1 ethylenically unsaturated double bond, and (meth)acryloyl) C.sub.1-C.sub.6 moiety, wherein the C.sub.1-C.sub.6 part of said moieties is normal chained, branched or cyclised and is optionally substituted by one or more moieties selected from the group consisting of C.sub.1-C.sub.4 hydrocarbon, aryl and aralkyl and optionally comprises one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur and optionally comprises one or more carbonyl moieties.

(30) The aldehyde, with general formula RCOH, for being used in the method of the present invention, is selected from the compounds in which R is an hydrogen, an aliphatic, araliphatic, aromatic or heterocyclic moiety and in which the total number of carbon and hetero atoms assumes preferably a value of from 1 to 11. Aliphatic moieties are especially alkyl moieties, preferable those with 1 to 6 carbon atoms, examples being methyl, ethyl, propyl, butyl. The aliphatic moieties can also be branched, examples being isobutyl. Aromatic moieties are for example phenyl or ?- or ?-naphtyl and heterocyclic moieties are for example furfuryl. The aldehyde can also have one or more substituents, such as for example the alkoxy group.

(31) Examples of aldehydes with saturated aliphatic moieties are formaldehyde, acetaldehyde and butyraldehyde. Examples of aldehydes with substituted saturated aliphatic moieties are methoxyacetaldehyde and 3-methoxypropionaldehyde. Examples of aldehydes with araliphatic moieties are phenylacetaldehyde and phenylpropionaldehyde. Examples of aldehydes with aromatic or heterocyclic moieties are benzaldehyde, furfural and 4-methoxyfurfural.

(32) The ketone, with general formula RCOR, for being used in the method of the present invention is a symmetrical or asymmetrical compound with R and R being independently selected from aliphatic, araliphatic, cyclic or aromatic hydrocarbon moieties, the total number of carbon atoms assuming preferably a value of from 1 to 12. The aliphatic moieties are straight-chain or branched and preferably saturated alkyl moieties such as for example methyl, ethyl, propyl and isobutyl. Araliphatic moieties are for example benzyl or phenethyl and aromatic moieties are for example ?- or ?-naphtyl and preferably phenyl. The ketones can also have one or more substituents such as for example the alkoxy group.

(33) Examples of ketones with saturated aliphatic moieties are acetone, methylethylketone, methylisobutylketone; examples of ketones with substituted aliphatic moieties are methoxyacetone. An example of ketones with araliphatic moieties is benzylacetone; examples of ketones with cyclic moieties are cyclohexanone and cyclopentanone while examples of ketones with aromatic moieties are acetophenone and 4-methoxy-acetophenone.

(34) Formaldehyde is used with special preference as aldehyde. Formaldehyde known as oxymethylene having the formula CH.sub.2O is produced and sold as water solutions containing variable, frequently minor, e.g. 0.3-3%, amounts of methanol and are typically reported on a 37% formaldehyde basis although different concentrations can be used. Formaldehyde solutions exist as a mixture of oligomers. Such formaldehyde precursors can, for example, be represented by paraformaldehyde, a solid mixture of linear poly(oxymethylene glycols) of usually fairly short, n=8-100, chain length, and cyclic trimer of formaldehyde designated by the terms 1,3,5-trioxane. Concentrations of liquid formaldehyde above about 37% need to be kept above room temperature to prevent the precipitation of formaldehyde polymers. The temperature necessary to maintain a clear solution and prevent separation of solid polymer increases from room temperature as the solution concentration is increased above about 37%.

(35) While formaldehyde is preferably added as 37% by weight solution in water, known as formalin, it also can be added as an aqueous solution with a formaldehyde concentration different from 37% by weight or as a solid such a for example as paraformaldehyde or as 1,3,5-trioxane.

(36) When formaldehyde is used as an aqueous solution, it goes without saying that the aminoalkylol intermediate first has to be isolated before it is put into reaction with the POP anhydride moiety comprising compound with the proviso that the step of isolating the aminoalkylol can be omitted for those cases where the water quantities, present in the aqueous formaldehyde solution are in accordance with those required for transforming a first POP anhydride moiety comprising compound into a modified POP-anhydride moiety comprising compound through partially hydrolysis of said first POP anhydride moiety comprising compound whereupon said modified POP anhydride moiety comprising compound will react with the aminoalkylol to form aminoalkylenephosphonic acid.

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

(38) The homogeneous Br?nsted acid preferably is selected from the group consisting of methanesulfonic acid, fluoromethanesulfonic acid, trichloromethanesulfonic acid, trifluoromethanesulfonic 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, phosphoric acid, and mixtures thereof. The homogeneous Br?nsted acid is preferably methanesulfonic acid.

(39) The heterogeneous Br?nsted acid is preferably selected from the group consisting of:

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

(41) (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;

(42) (iii) organic sulfonic, carboxylic and phosphonic Br?nsted acids which are substantially immiscible in the reaction medium at the reaction temperature;

(43) (iv) an acid catalyst derived from: the interaction of a solid support having a lone pair of electrons onto which is deposited an organic Br?nsted 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 Br?nsted acid group or a precursor therefore; 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.

(44) Preferred homogeneous Lewis acids can be selected from metal salts having the general formula:
MX.sub.n
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 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, AlCl3, 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 weakly 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.

(45) 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.

(46) Typical examples of suitable organic solvents to be used in the method of the invention are anisole; acetic acid; 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; non-reactive ionic liquids like 1-n-butyl-imidazolium trifluoromethanesulfonate, and 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide.

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

(48) The method of the present invention is started by mixing the HNR.sup.1R.sup.2 comprising compound, the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, and the aldehyde or ketone, preferable formaldehyde, in the presence of an acid catalyst and optionally a solvent, the ratio of equivalents of >NH moieties to moles of aldehyde or ketone is comprised between 0.9 and 1.5 and preferably between 1.1 and 1.4; the ratio of equivalents of >NH moieties to POP anhydride moieties is comprised between 0.3 and 2.0 and preferably between 0.5 and 1.5.

(49) In the present invention, the method may comprise the steps of forming a reaction mixture by the alternating gradual addition of aldehyde or ketone, preferable formaldehyde, and the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, in portions, to the HNR.sup.1R.sup.2 comprising compound in the presence of an acid catalyst and optionally a solvent.

(50) In a particular embodiment of the present invention the method comprises the steps of forming a reaction mixture by mixing the HNR.sup.1R.sup.2 comprising compound and the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, in the presence of a acid catalyst and optionally a solvent; subsequently the aldehyde or ketone, preferable formaldehyde, is gradually added to the reaction mixture (Example 19).

(51) In general the reaction is performed at a temperature comprised between 20? C. and 120? C. and preferably between 50? C. and 110? C. for a period of time comprised between 30 minutes and 24 hours

(52) In the present invention, the method may comprise the steps of forming a reaction mixture by mixing an aldehyde or ketone, preferable formaldehyde, and the HNR.sup.1R.sup.2 comprising compound in the presence of an acid catalyst and optionally a solvent; subsequently the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, is gradually added to the reaction mixture (Example 12 and 13, Example 14 to 18 and Example 20).

(53) In the present invention, the method may also comprise the steps of forming a reaction mixture by mixing an aldehyde or ketone, preferable formaldehyde, and the HNR.sup.1R.sup.2 comprising compound in the presence of an acid catalyst and optionally a solvent; isolating an optionally purifying the aminoalkylol moiety comprising compound and subsequently gradually adding the POP anhydride moiety comprising compound, preferable tetraphosphorus hexaoxide, to the amino alkylol moiety comprising compound in the presence of an acid catalyst and optionally a solvent (Example 1 to 11).

(54) In general, the addition of an aldehyde or ketone, preferably formaldehyde, to the reaction mixture is performed at a temperature comprised between about 20? C. and about 120? C. and preferably between about 40? C. and 100? C. and, after completion of the aldehyde or ketone addition, the reaction mixture is kept at that temperature, for a period of time comprised between about 10 minutes and about 24 hours and preferably between about 1 hour and about 20 hours.

(55) In general, the addition of the POP anhydride moiety comprising compound, preferably tetraphosphorus hexaoxide to the reaction mixture is performed at a temperature comprised between about 20? C. and about 120? C. and preferably between about 40? C. and about 100? C. and, after the completion of the tetraphosphorus hexaoxide addition, the reaction mixture is kept at that temperature for a period of time comprised between about 10 minutes and about 24 hours and preferably between about 1 hour and about 20 hours.

(56) After completion of the conversion of the HNR.sup.1R.sup.2 comprising compound into aminoalkylenephosphonic acid comprising compound, water is optionally added to the reaction mixture in order to hydrolyse the unreacted POP anhydride moieties, if present and optionally to convert the aminoalkylene phosphonic acid comprising compound or its dehydrated forms or their phosphonate esters in its hydrolysed form, such as in Example 14 to 17 where N-phosphonomethyl-2,5-oxazolidinedione is hydrolysed into N-(phosphonomethyl)glycine with the formation of carbon dioxide or in Example 11 where N,N-bis(phosphonomethyl)urea is hydrolysed into aminomethylphosphonic acid with the formation of carbon dioxide.

(57) The hydrolysis is performed at a temperature comprised between about 20? C. and about 150? C., preferably between about 40? C. and about 100? C., for a period comprised between about 10 minutes and about 72 hours and preferably between about 1 hour and about 10 hours.

(58) Unreacted POP anhydride moieties may be the result of an incomplete conversion or of the addition of an excess of POP anhydride group comprising compounds, forming the reaction mixture.

(59) For the case of a substantial complete conversion and a stoichiometric loading of the reactants, the addition of water and thus the hydrolysis step can be omitted.

(60) The hydrolysis preferably is performed for a reaction mixture standing at a pH comprised between 4 and 7 what in general is obtained through the addition of an alkali hydroxides, preferable sodium or potassium hydroxide.

EXAMPLES

(61) The following illustrative examples are meant to exemplify but are not destined to limit the scope the present invention.

Example 1

(62) In a round-bottom flask equipped with a mechanical stirrer, a thermometer and a condenser 3.56 g (40 mmole) N-hydroxymethylacetamide was mixed with 10 ml acetonitrile. Slowly, 2.20 g (10 mmole) P.sub.4O.sub.6 was added. Afterwards the reaction mixture was heated to 80? C. for 1 hour. Then 0.15 g (1 mmole) trifluoromethanesulfonic acid was added and stirring was continued for 2 hours at 80? C. All volatiles were removed in vacuum and the residue was dissolved in 5 ml H.sub.2O and 10 ml NaOH solution (50% w/w in H.sub.2O) and heated to 100? C. for 2 hours. The obtained solution was analysed by .sup.31P-NMR spectroscopy. Aminomethylphosphonic acid was detected at 15.5% w/w.

Example 2

(63) Using the equipment of Example 1, 1.77 g (10 mmole) of N-hydroxymethylphthalimide was mixed with 8.5 ml of methanesulfonic acid at 60? C. under N2. Slowly, 0.285 ml (2.5 mmole) of P.sub.4O.sub.6 was added. Afterwards the reaction mixture was heated at 85? C. overnight. Then 3 ml of water were added and the mixture was heated for 1 hour at 80? C. The solution was diluted with water and brought to pH 5.4 by addition of sodium hydroxide. The mixture was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-Phthalimidomethylphosphonic acid was detected at 11.5% w/w.

(64) In table 1 a series of examples, prepared according to the method of the present invention and using the equipment and the method of Example 1 and Example 2, are reported.

(65) In this table:

(66) Column 1: indicates the identification number of the example. Column 2: indicates the type of aminoalkylol moiety comprising compound put into reaction with tetraphosphorus hexaoxide. Column 3: indicates the number of mmoles of aminoalkylol moiety comprising compound with into brackets the number of aminoalkylol milliequivalents. Column 4: indicates the type of acid catalyst and of solvent used. Column 5: indicates the number of mmoles of acid catalyst. Column 6: indicates the number of mmoles of tetraphosphorus hexaoxide. Column 7: indicates the ratio of mmoles of aminoalkylol comprising compound to mmoles of tetraphosphorus hexaoxide with into brackets the ratio of aminoalkylol milliequivalents to the mmoles of tetraphosphorus hexaoxide. Column 8: indicates the ratio of mmoles of acid catalyst to mmoles of aminoalkylol moiety comprising compound with into brackets the ratio of mmoles of acid catalyst to the milliequivalents of aminoalkylol moieties. Column 9: indicates the ratio of mmoles of acid catalyst to mmoles of tetraphosphorus hexaoxide. Column 10: indicates the temperature (? C.) at which the mixing of the HNR.sup.1R.sup.2 moiety comprising compound, the aldehyde and the POP anhydride comprising compound, in the presence of a solvent, is performed. Column 11: indicates the temperature (? C.) and time (hours) conditions of the reaction mixture once all the components have been added. Column 12: indicates the temperature (? C.) and time (hours) conditions of the hydrolysis. Column 13: indicates the reaction yield, in % by weight, as measured by .sup.1H-NMR and .sup.31P-NMR spectroscopy.

(67) The aminomethylenephosphonic acid moiety comprising compound prepared in the examples of table 1 are: Example 1: aminomethylphosphonic acid Example 2 and 3: N-phthalimidomethylphosphonic acid Example 4: N-phosphonomethyl, N-phenyl hydantoin Example 5: N-phosphonomethyloxazolidinone Example 6 to 10: N-phosphonomethylpyrrolidinone Example 11: N,N-bis(phosphonomethyl)urea further hydrolised into aminomethylphosphonic acid

Example 12

(68) Using the equipment of Example 1, 1 equivalent of glycine methyl ester hydrochloride was mixed with 1.5 equivalents of paraformaldehyde in 18.5 equivalents of methanesulfonic acid at 50? C. for 1 hour and then at 75? C. for 25 minutes under N2. The temperature was adjusted to 25? C. before the slowly addition of 0.25 equivalent of P.sub.4O.sub.6 while keeping the temperature of the reaction medium under 35? C. Afterwards the reaction mixture was heated to 60? C. for 1 hour. Then 30 equivalents of water were added and the mixture was heated at 110? C. for 30 minutes. The solution was diluted with water and brought to pH 5.4. The mixture was analysed by .sup.31P-NMR spectroscopy. N-(Phosphonomethyl)glycine was detected at 5.2% mol.

Example 13

(69) Using the equipment of Example 1, 0.8 equivalent of N-(2-aminoethyl)ethane-1,2-diamine was mixed with 5.35 equivalents of paraformaldehyde in acetonitrile containing 5 equivalents of trifluoroacetic acid. The mixture was stirred for 40 minutes at 65? C. under N2. The reaction medium was cooled to 35? C. and 1.0 equivalent of P.sub.4O.sub.6 was slowly added while the temperature was maintained below 35? C. Afterwards the reaction mixture was heated to 60? C. for 20 minutes. Then an excess of water was added and the mixture was heated at 85? C. for 15 minutes. The solution was diluted with water and brought to pH 5.4. The mixture was analysed by .sup.31P-NMR spectroscopy. Diethylenetriamine penta(methylenephosphonic acid) was detected at 10% mole.

Example 14

(70) Using the equipment of Example 1, 0.30 g (9.9 mmole) paraformaldehyde was mixed with 8 ml trifluoroacetic acid. Subsequently the reaction mixture was heated to 50? C. and 1.00 g (9.9 mmole) 2,5-oxazolidinedione was added. Afterwards the reaction mixture was stirred for 1 hour at 50? C. Slowly, 0.55 g (2.5 mmole) P.sub.4O.sub.6 was added and stirring was continued for 24 hours at 50? C. 10 ml H.sub.2O was added and stirring was continued for 72 hours at 50? C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-(phosphonomethyl)glycine was detected 42.5% w/w.

Example 15

(71) Using the equipment of Example 1, 1.00 g (9.9 mmole) 2,5-oxazolidinedione was mixed with 8 ml trifluoroacetic acid. Subsequently 0.30 g (9.9 mmole) paraformaldehyde was added. Afterwards the reaction mixture was stirred for 24 hours at ambient temperature. Then the temperature was increased to 50? C. and slowly 0.55 g (2.5 mmole) P.sub.4O.sub.6 was added. Stirring was continued for 24 hours at 50? C. 10 ml H.sub.2O was added and stirring was continued for 72 hours at 50? C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-(phosphonomethyl)glycine was detected 44.7% w/w.

Example 16

(72) Using the equipment of Example 1, 1.00 g (9.9 mmole) 2,5-oxazolidinedione was mixed with 8 ml trifluoroacetic acid. Subsequently 0.30 g (9.9 mmole) paraformaldehyde was added. Afterwards the reaction mixture was stirred for 1 hour at ambient temperature. Slowly, 0.55 g (2.5 mmole) P.sub.4O.sub.6 was added. Stirring was continued for 24 hours at 60? C. 10 ml H.sub.2O was added and stirring was continued for 8 hours at 60? C. The obtained solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-(phosphonomethyl)glycine was detected 34.9% w/w.

Example 17

(73) Using the equipment of Example 1, 1.00 g (9.9 mmole) 2,5-oxazolidinedione was mixed with 8 ml toluene. Subsequently 0.30 g (9.9 mmole) paraformaldehyde was added. Afterwards the reaction mixture was stirred for 3 hours at 80? C. Slowly 1 ml methanesulfonic acid and 0.55 g (2.5 mmole) P.sub.4O.sub.6 were added. Stirring was continued for 5 hours at 60? C. 10 ml H.sub.2O was added and stirring was continued for 8 hours at 60? C. The aqueous solution was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. N-(Phosphonomethyl)glycine was detected 5.6% w/w.

Example 18

(74) Using the equipment of Example 1, 7.36 g (245.2 mmole) paraformaldehyde was mixed with 64 ml methanesulfonic acid. Subsequently the reaction mixture was heated to 40? C. and 3.69 g (61.5 mmole) ethylenediamine was added slowly. Afterwards the reaction mixture was heated to 50? C. and 13.55 g (61.6 mmole) P.sub.4O.sub.6 was added slowly. The reaction mixture was heated to 85? C. for 1 hour. At ambient temperature 35 ml H.sub.2O was added and the obtained solution and the solid were analysed by .sup.31P-NMR spectroscopy. Ethylenediamine-tetramethylenephosphonic acid was detected at 36.6% w/w.

Example 19

(75) Using the equipment of Example 1, 11.08 g (184.4 mmole) ethylenediamine was mixed with 64 ml methanesulfonic acid. Subsequently the reaction mixture was heated to 70? C. and 40.64 g (184.7 mmole) P.sub.4O.sub.6 was added slowly. Afterwards the reaction mixture was heated to 105? C. and 60.4 g (735.5 mmole) paraformaldehyde solution (36.6% w/w in H.sub.2O) was added over 30 minutes. The reaction mixture was heated to 105? C. for 1 hour. At ambient temperature 25 ml H.sub.2O was added and the obtained solution and the solid were analysed by .sup.31P-NMR spectroscopy. Ethylenediamine-tetramethylenephosphonic acid was detected at 57.5% w/w.

Example 20

(76) Using the equipment of Example 1, 7.36 g (245.2 mmole) paraformaldehyde was mixed with 64 ml methanesulfonic acid. Subsequently the reaction mixture was heated to 40? C. and 3.69 g (61.5 mmole) ethylenediamine was added slowly. Afterwards the reaction mixture was heated to 55? C. and 13.55 g (61.6 mmole) P.sub.4O.sub.6 was added slowly. The reaction mixture was heated to 80? C. for 3 hours. At ambient temperature 35 ml H.sub.2O was added and the obtained solution and the solid were analysed by .sup.31P-NMR spectroscopy. Ethylenediamine-tetramethylene phosphonic acid was detected at 31.9% w/w.

Example 21

(77) Using the equipment of Example 1, 4.24 g (40.0 mmole) benzaldehyde, 3.48 (40.0 mmole) morpholine and 0.12 g (0.8 mmole) trifluoromethanesulfonic acid were mixed with 10 ml 1,4-dioxane. Subsequently, the reaction mixture was stirred for 48 hours at ambient temperature. Then 2.20 g (10.0 mmole) P.sub.4O.sub.6 was added slowly followed by 0.48 g (3.2 mmole) trifluoromethane sulfonic acid. The reaction mixture was heated to 80? C. for 1 hour. At ambient temperature 20 ml H.sub.2O was added; the obtained solution was evaporated to dryness and the solid was analysed by .sup.1H- and .sup.31P-NMR spectroscopy. 4-Morpholinyl-phenyl-methylphosphonic acid was detected at 72.9% w/w.

(78) In table 2 examples 12 to 21, prepared according to the present invention are summarized. In this table the respective columns have the same meaning as the corresponding columns of table 1.

(79) In table 2, example 12 describes the synthesis of N-(hydroxymethyl)glycine methyl ester from reaction of glycine methyl ester and formaldehyde followed by the formation of N-(phosphonomethyl)glycine through reaction with tetraphosphorus hexaoxide. example 13 describes the synthesis of N,N,N,N,N hydroxymethyl-(2-aminoethyl)ethane-1,2-diamine followed by the formation of N,N,N,N,N-phosphonomethyl-(2-aminoethyl)ethane-1,2-diamine through reaction with tetraphosphorus hexaoxide. example 14 to Example 17 describe the synthesis of N-hydroxymethyl-2,5-oxazolidinedione from reaction of 2,5-oxazolidinedione and formaldehyde followed by the formation of N-(phosphonomethyl)glycine through reaction with tetraphosphorus hexaoxide. example 18 to 20 describe the synthesis of ethylenediamine-tetramethylenephosphonic acid from reaction of ethylenediamine, formaldehyde and tetraphosphorus hexaoxide in the presence of an acid catalyst wherein in example 18 and 20 formaldehyde and ethylenediamine are first reacted with the formation of N,N,N,N tetrakis(hydroxymethyl) ethanediamine followed by the reaction with tetraphosphorus hexaoxide and wherein in example 19 ethylenediamine and tetraphosphorus hexaoxide are first reacted followed by the addition of formaldehyde. example 21 describes the synthesis of 4-morpholinyl-phenylmethanol from the reaction of morpholine and benzaldehyde, in the presence of an acid catalyst, followed by the formation of 4-morpholinyl-phenyl-methylphosphonic acid through the reaction with tetraphosphorus hexaoxide.

(80) TABLE-US-00001 TABLE 1 OH Cata. P.sub.4O.sub.6 OH Cata Cata T.sub.1 T.sub.2/time T.sub.3/time Yield Ex Aminoalkylol (mole) Solvent (mole) (mole) P.sub.4O.sub.6 OH P.sub.4O.sub.6 ? C. ? C./hrs ? C./hrs (%) 1 N-hydroxymethyl 40 Trifluoromethanesulfonic 1 10 4.0 0.025 0.1 25 80/3 100/2 15.5 acetamide acid Acetonitrile (10 ml) 2 N-hydroxymethyl 10 Methanesulfonic acid 130 2.5 4.0 13 52 60 85/16 80/1 11.5 phthalimide 3 N-hydroxymethyl 40 Trifluoromethanesulfonic 1 10 4.0 0.03 0.1 25 80/8 25/1 90.4 phthalimide acid 1,4-dioxane (10 ml) 4 N-hydroxymethyl-N- 10 Methanesulfonic acid 108 2.7 3.7 10.8 40.0 40 40/16 40/1 18.5 phenyl hydantoin 5 N-hydroxymethyl 15 Methanesulfonic acid 123 3.9 3.8 8.2 31.6 25 60/16 25/1 39.7 oxazolidinone 6 N-hydroxymethyl 30 Methanesulfonic acid 308 7.4 4.1 10.3 41.6 25 80/16 25/1 94.1 pyrrolidinone 7 N-hydroxymethyl 20 Trifluoromethanesulfonic 170 4.9 4.1 8.5 34.7 25 80/16 25/1 73.0 pyrrolidinone acid 8 N-hydroxymethyl 30 Trifluoroacetic acid 313 7.4 4.1 104 42.3 25 70/16 25/1 94.9 pyrrolidinone 9 N-hydroxymethyl 30 Trifluoromethanesulfonic 6 7.4 4.1 0.2 0.8 25 70/16 25/1 85.7 pyrrolidinone acid 1,4-dioxane (25 ml) 10 N-hydroxymethyl 30 Trifluoromethanesulfonic 6 7.4 4.1 0.2 0.8 25 70/16 25/1 96 pyrrolidinone acid acetonitrile (25 ml) 11 N,N-bismethylol 40 Methanesulfonic acid 308 10 4.0 7.7 30.8 70 80/4 150/8 34.8 urea (80) (8.0)

(81) TABLE-US-00002 TABLE 2 OH Cata. P.sub.4O.sub.6 OH Cata Cata T.sub.1 T.sub.2/time T.sub.3/time Yield Ex Aminoalkylol (mole) Solvent (mole) (mole) P.sub.4O.sub.6 OH P.sub.4O.sub.6 ? C. ? C./hrs ? C./hrs (%) 12 N-hydroxymethyl 1000 Methanesulfonic acid 18500 250 4.0 18.5 74 25 60/1 110/0.5 5.2 glycine methylester 13 Diethylenetriamine 800 Trifluoroacetic acid 5000 250 3.2 6.25 20 35 60/0.33 85/0.25 10 penta(hydroxymethylene) (4000) (16) (1.25) 14 N-hydroxymethyl 2,5- 9.9 Trifluoroacetic acid 104 2.5 4.0 10.5 41.6 50 50/24 50/72 42.5 oxazolidinedione 15 N-hydroxymethyl 2,5- 9.9 Trifluoroacetic acid 104 2.5 4.0 10.5 41.6 50 50/24 50/72 44.7 oxazolidinedione 16 N-hydroxymethyl 2,5- 9.9 Trifluoroacetic acid 104 2.5 4.0 10.5 41.6 25 60/24 60/8 34.9 oxazolidinedione 17 N-hydroxymethyl 2,5- 9.9 Methanesulfonic acid 15 2.5 4.0 1.5 6.0 80 60/5 60/8 5.6 oxazolidinedione toluene (8 ml) 18 N,N,NN hydroxymethyl 61.5 Methanesulfonic acid 985 61.6 1.0 16.0 16.0 50 85/1 25/1 36.6 ethylenediamine (246) (4.0) (4.0) 19 N,N,NN hydroxymethyl 184.4 Methanesulfonic acid 985 184.7 1.0 5.3 5.3 70 105/1 25/1 57.5 ethylenediamine (738) (4.0) (1.3) 20 N,N,NN hydroxymethyl 61.5 Methanesulfonic acid 985 61.6 1.0 16.0 16.0 55 80/3 25/1 31.9 ethylenediamine (246) (4.0) (4.0) 21 4-morpholinyl- 40.0 Trifluoromethane- 4.0 10.0 4.0 0.1 0.4 25 80/1 25/1 72.9 phenylmethanol sulfonic acid 1,4-dioxane (10 ml)