Method for the synthesis of alpha-aminoalkylenephosphonic acid

Abstract

A method for the synthesis of alpha-aminoalkylenephosphonic acid or its phosphonate esters including the steps of forming a reaction mixture by mixing a P—O—P anhydride moiety including a compound, having one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V), an aminoalkanecarboxylic acid and an acid catalyst, wherein the reaction mixture includes an equivalent ratio of alpha-aminoalkylene carboxylic acid to P—O—P anhydride moieties of at least 0.2, and recovering the resulting alpha-aminoalkylene phosphonic acid compound or an ester thereof from the reaction mixture.

1 . A method for the synthesis of an alpha-aminoalkylenephosphonic acid or an ester thereof comprising the steps of:
 a) forming a reaction mixture by mixing a compound comprising one or more P—O—P anhydride moieties, said moieties comprising one P-atom at the oxidation state (+III) and the other P-atom at the oxidation state (+III) or (+V), an alpha-aminoalkylenecarboxylic acid and an acid catalyst, wherein   said compound comprising one or more P—O—P anhydride moieties is selected from the group consisting of:   tetraphosphorus hexaoxide, tetraethylpyrophosphite, a compound obtained from the combination of one or more compounds comprising one or more P—OH moieties with one or more compounds comprising one or more P—O—P anhydride moieties, wherein the P atom of one or more compounds is at the oxidation state (+III) and wherein the compounds having one or more P—OH moieties are accessible by tautomerization of a >P(═O)H moiety; and   a compound obtained from the combination of one or more compounds having 2 or more P—O—P moieties and water, wherein the P—O—P moieties have one P atom at the oxidation state (+III) and one P-atom at the oxidation state (+III) or (+V);   and wherein
 said reaction mixture comprises an equivalent ratio of alpha-aminoalkylenecarboxylic acid to P—O—P anhydride moieties of at least 0.2, 
   and
 b) recovering the resulting alpha-aminoalkylenephosphonic acid compound or an ester thereof from said reaction mixture. 
   
     
     
         2 . The method according to  claim 1  wherein a reaction mixture is formed by gradually adding a P—O—P 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), to a mixture comprising an alpha-aminoalkanecarboxylic acid and an acid catalyst. 
     
     
         3 . The method according to  claim 1  wherein a reaction mixture is formed by gradually adding a mixture comprising an alpha-aminoalkanecarboxylic acid and an acid catalyst to a P—O—P 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). 
     
     
         4 . The method according to  claim 1  comprising the additional steps of:
 adding water to the reaction mixture after completion of the conversion of alpha-aminoalkylene carboxylic acid into alpha-aminoalkylene phosphonic acid; 
 bringing the reaction mixture comprising the added water, to a temperature comprised between 20° C. and 100° 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 P—O—P anhydride moiety comprising compound is selected from the group consisting of tetraphosphorus hexaoxide, tetraethylpyrophosphite, and the P—O—P anhydride moiety comprising compound obtained from the combination of phosphorous acid and tetraphosphorus hexaoxide, of phosphorous acid and tetraphosphorus decaoxide, of dimethylphosphite and tetraphosphorus decaoxide and of tetraphosphorus hexaoxide and water. 
     
     
         6 . The method according to  claim 1 , wherein the P—O—P anhydride moiety comprising compound is tetraphosphorus hexaoxide. 
     
     
         7 . The method according to  claim 1 , wherein the alpha-aminoalkylene carboxylic acid comprising compound has the general formula:
   R 1 —N(R 2 )—CR 3 R 4 —CO 2 M
   wherein R 1  can be a substituted C or substituted S atom; R 2  can be a H atom, a substituted C or a substituted S atom; R 3  and R 4  can be independently a H atom or a substituted C atom: M can be a H atom or an alkaline or alkaline earth metal.   
     
     
         8 . The method according to  claim 1 , wherein the alpha-aminoalkylene carboxylic acid comprising compound is selected from
 a) a compound wherein the N atom possesses a low basicity by substitution of the N atom with electron withdrawing groups or groups that are able to partly delocalise the N-lone pair;   b) a polyamine wherein at least two N atoms are present and each N atom is separated by at least two carbon atoms from the next neighbouring N atom;   c) a compound wherein the N atom is substituted by alkyl groups.   
     
     
         9 . The method according to  claim 1 , wherein the alpha-aminoalkylene carboxylic acid comprising compound is selected from
 a) nitrilotriacetic acid, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, N-benzyliminodiacetic acid, N-methyliminodiacetic acid, iminodiacetic acid, N,N-bis(carboxymethyl)-1-glutamic acid, trisodium-N,N-bis(carboxymethyl)-alanine, N-cyanomethyl alanine, N,N-bis(cyanomethyl)-glycine, 4-morpholinoacetic acid, pyroglutamic acid, N-acetyl glycine, N,N-bis(carboxymethyl)-6-aminohexanoic acid, N-phenyl glycine, N-tosyl glycine, trans-1,2-cyclohexyldiaminotetraacetic acid monohydrate, N-phosphonomethyliminodiacetic acid, iminodiacetic acid grafted on resin such as for example acidified Amberlite IRC748i;   b) 1,4,7,10-tetraazadodecane-1,4,7,10-tetraacetic acid, trans-1,2-cyclohexyldiaminotetracetic acid monohydrate;   c) N,N′-dimethylglycine.   
     
     
         10 . The method according to  claim 1 , wherein the acid catalyst is a homogeneous Brønsted acid catalyst preferably 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. 
     
     
         11 . The method according to  claim 1 , wherein the acid catalyst is a heterogeneous Brønsted acid catalyst selected from the group consisting of:
 (i) solid acidic metal oxide combinations as such or supported onto 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 3 H moieties onto the aromatic group and perfluorinated resins carrying carboxylic and/or sulfonic acid groups; 
 (iii) organic sulfonic, carboxylic and phosphonic Brønsted 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 Brønsted 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 Brønsted acid group or a precursor therefore; and 
 (v) heterogeneous heteropolyacids of the general formula H x PM y O 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 Lewis acid catalyst selected from the group consisting of LiN(CF 3 SO 2 ) 2 , Mg(OCF 3 SO 2 ) 2 , Al(OCF 3 SO 2 ) 3 , Bi(OCF 3 SO 2 ) 3 , Sc(OCF 3 SO 2 ) 3 . 
     
     
         13 . The method according to  claim 1 , wherein the reaction mixture comprises a diluent selected from the group consisting of 1,4-dioxane, toluene, ethylacetate, sulfolane, acetonitrile, 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide, or a mixture thereof. 
     
     
         14 . The method according to  claim 1 , wherein the equivalent ratio of alpha-aminoalkylenecarboxylic acid to P—O—P anhydride moiety is comprised between 0.2 and 4.5, preferably between 0.3 and 3.0 and more preferably between 0.5 and 1.5. 
     
     
         15 . The method according to  claim 1 , wherein the ratio of the alpha-aminoalkylenecarboxylic acid equivalents to the moles of tetraphosphorus hexaoxide is comprised between 1.0 and 12.0, preferably between 1.5 and 8.0 and more preferably between 2.0 and 6.0. 
     
     
         16 . The method according to  claim 1 , wherein the ratio of the moles of acid catalyst to the alpha-aminoalkylenecarboxylic acid equivalents is comprised between 0.01 and 11.0, preferably between 0.1 and 9.0, more preferably between 1.0 and 7.0 and most preferably between 2.0 and 5.0. 
     
     
         17 . The method according to  claim 1 , wherein the P—O—P anhydride moiety comprising compound is mixed with the mixture of alpha-aminoalkylene carboxylic acid and acid catalyst, at a temperature comprised between 20° C. and 120° C., preferably between 20° C. and 80° C. 
     
     
         18 . The method according to  claim 1 , wherein the reaction mixture, after completion of the mixing, is maintained at a temperature comprised between 20° C. and 100° C., preferably between 40° C. and 90° C. and more preferably between 50° C. and 80° for a period of time comprised between 10 minutes and 72 hours. 
     
     
         19 . The method according to  claim 1 , wherein the obtained alpha-aminoalkylenephosphonic acid is selected from the group consisting of aminomethylphosphonic acid, (N,N-dimethylamino)methylphosphonic acid, phthalimidomethylphosphonic acid, N-phenyl-aminomethylphosphonic acid, N-tosyl-aminomethylphosphonic acid, N-phosphonomethyl glycine, N-(1-phosphonomethyl)-glycine, phosphonomethyliminodiacetic acid, 4-morpholinemethylphosphonic acid, 4-amino-4-phosphonobutyric acid, 5-phosphono-2-pyrrolidone, N,N-bis(phosphonomethyl)-6-amino-hexanoic acid, N,N-bis(phosphonomethyl)-4-amino-4-phosphono-butyric acid, N,N-bis(phosphonomethyl)-4-amino-glutamic acid, N,N-bis(phosphonomethyl)-1-amino-ethyl-phosphonic acid, imino (bismethylenephosphonic acid), N-methyl-imino (bismethylenephosphonic acid), N-benzyl-imino (bismethylenephosphonic acid), aminotrismethylenephosphonic acid, ethylene diamino tetra-(methylene phosphonic acid), trans-1,2-cyclohexyldiaminotetramethylenephosphonic acid, 1,4,7,10-tetraazadodecane-1,4,7, 10-tetramethylenephosphonic acid, N-methyl-iminodiphosphonic acid. 
     
     
         20 . The method according to  claim 1 , wherein carbon monoxide is recovered and reused. 
     
     
         21 . The method comprising the use of alpha-aminoalkylenephosphonic acid or its esters, obtained from the method according to  claim 1 , as scale inhibitor, dispersing agent, sequestering agent, detergent additive, marine-oil drilling adjuvant, pharmaceutical component, for ion exchange when grafted on an organic or inorganic support, as ligands to immobilize homogeneous metallic catalysts and as heterogeneous acid catalysts.