3-Aminopropylphosphonic acid

(3-aminopropyl)phosphonic acid is a phosphonic acid in which the hydrogen attached to the phosphorus of phosphonic acid is substituted by a 3-aminopropyl group. It is a partial agonist of GABAB receptors. It has a role as a GABAB receptor agonist. It is a primary amino compound and a member of phosphonic acids. It derives from a phosphonic acid. It is a tautomer of a (3-aminopropyl)phosphonic acid zwitterion.

Aminotrimethylene phosphonic acid (ATMP) was prepared by reacting phosphorous acid, ammonia and formaldehyde in the presence of a methanesulfonic acid catalyst. The individual components were used in the recited proportions. Reactant g mole(s) Phosphorous acid 100.45 1.225 Methanesulfonic acid 15.43 0.161 Ammonia (25 percent solution) 27.2 0.4 Formaldehyde (36.6 percent solution) 103.27 1.26 Water 58.07 - The phosphorous acid was first added to the reactor followed by the water, the methanesulfonic acid and the ammonia. The reaction mixture so prepared was subsequently heated to 105 °C at which temperature the gradual addition of the formaldehyde was started. The formaldehyde was added in a period of 2 hours. The reaction was, after the addition of the formaldehyde, continued under reflux conditions for a further period of 2 hours. The reaction product was analyzed by means of a 31P-NMR spectroscopic method. It was found that ATMP was formed with a yield of 59.1 percent.Additional ATMP preparations were conducted thereby using the method set forth in and conducting the reactions in accordance with that except that the methanesulfonic acid catalysts were utilized in the following levels. Example g mole(s) 2 61.85 0.644 3 42.33 0.441 The reaction product formed, analyzed as described in Example 1, showed a yield of ATMP of 76.8 percent Example 3 72.7 percent. These Examples (1-3) demonstrate the unexpected benefits of the inventive technology and show that the aminopolymethylene phosphonic acids can be prepared under exclusion of hydrohalogenic reactants in a short cycle time and in high yields as compared to state-of-the-art methods using the PClAminopolymethylene phosphonic acids were prepared, in accordance with Example 1, having the following compositions. Reactant Example 14 15 16 17 Phosphorous acid - g 100.45 100.45 452.05 301.35 - mole 1.225 1.225 5.5125 3.67 Ammonia (25 percent solution) - g 27.2 27.2 122.4 81.6 - mole 0.4 0.4 1.8 1.2 Formaldehyde (36.6 percent solution) - g 103.27 103.27 464.7 309.8 -mole 1.26 1.26 5.67 3.77 Water added -g 30.0 58.07 none none The levels and species of catalysts used were as follows. Example Catalyst Species g mole(s) 14NaHSOAminopolymethylene phosphonic acids were prepared, in accordance with Example 1, having the following compositions. Reactant Example 14 15 16 17 Phosphorous acid - g 100.45 100.45 452.05 301.35 - mole 1.225 1.225 5.5125 3.67 Ammonia (25 percent solution) - g 27.2 27.2 122.4 81.6 - mole 0.4 0.4 1.8 1.2 Formaldehyde (36.6 percent solution) - g 103.27 103.27 464.7 309.8 -mole 1.26 1.26 5.67 3.77 Water added -g 30.0 58.07 none none The levels and species of catalysts used were as follows. Example Catalyst Species g mole(s) 14NaHSOExample 3.; An ATMP composition was made by reacting the listed ingredients in the stated proportions. Reactant g mole(s) Phosphorous acid 47.71 0.5697 Ammonia (32 percent solution) 10.08 0.1899 Formaldehyde (36.6 percent solution) 49.03 0.5981 Perfluoro-undecanoic acid 12.50 0.02215 The perfluoro-undecanoic acid catalyst is immiscible in the reaction medium at the reaction conditions. All the reactants, except the formaldehyde, were charged into a pressure autoclave before starting the heating. The formaldehyde was added starting at a temperature of 120 °C during a period of 2 hours. The reaction product, analyzed in accordance with the method of Example 1, contained the following major compounds. ATMP 58.6 percent N-MeIBMPA 14.6 percentHAdditional aminopolyalkylene phosphonic acid preparations were carried out as described for Examples 4-8, except as specifically recited below. The listed ingredients were used, in Examples 9-13, in identical levels as follows. Reactant g mole(s) Phosphorous acid 452.03 5.5125 Ammonia (25 percent solution) 122.4 1.8 Formaldehyde (36.6 percent solution) 464.71 5.67 The levels and species of catalyst and added water were selected as follows. Example Catalyst Added Water Species g mole(s) g 9CHExample 32. An aminopolymethylene phosphonic acid compound was prepared by reacting, in a closed vessel under autogeneous pressure built up, the listed ingredients in the manner described in Example 1. Reactant g/moles(s) Phosphorous acid 45.20/0.551 Methane sulfonic acid 13.48/0.140 Ammonia (32 percent solution) 9.56/0.18 Formaldehyde (36.6 percent solution) 46.47/0.567 10 percent of the ammonia was added together with the other ingredients whereas the remaining 90 percent of the ammonia was added together with the formaldehyde, starting from 105 °C, over a period of 3 hours. The reaction product analyzed as in contained the following compounds percent-ATMP 55.3 percent-N-MeIBMPA 4.6 percent-Phosphorous acid 17.5 Additional aminopolymethylene phosphonic acids were prepared, Examples 33-46, by reacting, in a closed vessel under autogeneous pressure built up, the listed ingredients in the stated proportions, as set forth in Example 1. Reactant g/mole(s) Example Phosphorous acid 90.40/1.102 all Ammonia (32 percent solution) 19.12/0.36 all Formaldehyde (36.6 percent solution) 92.94/1.134 all Methane sulfonic acid 26.96/0.281 33-44 idem 29.38/0.306 45 idem 14.99/0.153 46 The formaldehyde/ammonia additions in the individual Examples were as follows. Examples 33 10 percent of the ammonia was added at the start and 90 percent was added with the formaldehyde over a period of 90 minutes starting from 115 °C; 34 As in Example 33, except that 40 percent of the ammonia was added at the start and the formaldehyde/ammonia reactant was added over a period of 30 minutes; As in Example 34, except that the formaldehyde/ammonia was added starting from 120 °C; 36 As in Example 34 except that the formaldehyde/ammonia was added starting from 125 °C; 37 As in Example 33, except that the formaldehyde/ammonia was added starting from 115 °C over a period of 30 minutes; 38 As in Example 37, except that the formaldehyde/ammonia was added starting from 125 °C; 39 As in Example 38, except that the formaldehyde/ammonia was added over a period of 30 minutes starting from 120 °C; 40 As in Example 39, except that 30 percent of the ammonia was added at the start while the remaining 70 percent was added with the formaldehyde; 41 As in Example 37, except that 70 percent of the ammonia was added at the start and 30 percent with the formaldehyde; 42 As in Example 41, except that the formaldehyde/ammonia was added starting from 120 °C; 43 As in Example 42, except that the formaldehyde/ammonia was added over a period of 3 minutes starting from 115 °C; 44-46 As in Example 43, except that the formaldehyde/ammonia was added starting from 125 °C. The reaction products, analyzed as in Example 1, contained the following phosphonate compounds. Example percent-ATMP percent-N-MeIBMPApercent-HAminopolymethylene phosphonic acids were prepared, in accordance with Example 1, having the following compositions. Reactant Example 14 15 16 17 Phosphorous acid - g 100.45 100.45 452.05 301.35 - mole 1.225 1.225 5.5125 3.67 Ammonia (25 percent solution) - g 27.2 27.2 122.4 81.6 - mole 0.4 0.4 1.8 1.2 Formaldehyde (36.6 percent solution) - g 103.27 103.27 464.7 309.8 -mole 1.26 1.26 5.67 3.77 Water added -g 30.0 58.07 none none The levels and species of catalysts used were as follows. Example Catalyst Species g mole(s) 14NaHSOExample 32. An aminopolymethylene phosphonic acid compound was prepared by reacting, in a closed vessel under autogeneous pressure built up, the listed ingredients in the manner described in Example 1. Reactant g/moles(s) Phosphorous acid 45.20/0.551 Methane sulfonic acid 13.48/0.140 Ammonia (32 percent solution) 9.56/0.18 Formaldehyde (36.6 percent solution) 46.47/0.567 10 percent of the ammonia was added together with the other ingredients whereas the remaining 90 percent of the ammonia was added together with the formaldehyde, starting from 105 °C, over a period of 3 hours. The reaction product analyzed as in contained the following compounds percent-ATMP 55.3 percent-N-MeIBMPA 4.6 percent-Phosphorous acid 17.5 Additional aminopolymethylene phosphonic acids were prepared, Examples 33-46, by reacting, in a closed vessel under autogeneous pressure built up, the listed ingredients in the stated proportions, as set forth in Example 1. Reactant g/mole(s) Example Phosphorous acid 90.40/1.102 all Ammonia (32 percent solution) 19.12/0.36 all Formaldehyde (36.6 percent solution) 92.94/1.134 all Methane sulfonic acid 26.96/0.281 33-44 idem 29.38/0.306 45 idem 14.99/0.153 46 The formaldehyde/ammonia additions in the individual Examples were as follows. Examples 33 10 percent of the ammonia was added at the start and 90 percent was added with the formaldehyde over a period of 90 minutes starting from 115 °C; 34 As in Example 33, except that 40 percent of the ammonia was added at the start and the formaldehyde/ammonia reactant was added over a period of 30 minutes; As in Example 34, except that the formaldehyde/ammonia was added starting from 120 °C; 36 As in Example 34 except that the formaldehyde/ammonia was added starting from 125 °C; 37 As in Example 33, except that the formaldehyde/ammonia was added starting from 115 °C over a period of 30 minutes; 38 As in Example 37, except that the formaldehyde/ammonia was added starting from 125 °C; 39 As in Example 38, except that the formaldehyde/ammonia was added over a period of 30 minutes starting from 120 °C; 40 As in Example 39, except that 30 percent of the ammonia was added at the start while the remaining 70 percent was added with the formaldehyde; 41 As in Example 37, except that 70 percent of the ammonia was added at the start and 30 percent with the formaldehyde; 42 As in Example 41, except that the formaldehyde/ammonia was added starting from 120 °C; 43 As in Example 42, except that the formaldehyde/ammonia was added over a period of 3 minutes starting from 115 °C; 44-46 As in Example 43, except that the formaldehyde/ammonia was added starting from 125 °C. The reaction products, analyzed as in Example 1, contained the following phosphonate compounds. Example percent-ATMP percent-N-MeIBMPApercent-HExample 1.; Aminotrimethylene phosphonic acid (ATMP) was prepared by reacting phosphorous acid, ammonia and formaldehyde in the presence of a methanesulfonic acid catalyst. The individual components were used in the recited proportions. Reactant g mole(s) Phosphorous acid 100.45 1.225 Methanesulfonic acid 15.43 0.161 Ammonia (25 percent solution) 27.2 0.4 Formaldehyde (36.6 percent solution) 103.27 1.26 Water 58.07 - The phosphorous acid was first added to the reactor followed by the water, the methanesulfonic acid and the ammonia. The reaction mixture so prepared was subsequently heated to 105 °C at which temperature the gradual addition of the formaldehyde was started. The formaldehyde was added in a period of 2 hours. The reaction was, after the addition of the formaldehyde, continued under reflux conditions for a further period of 2 hours. The reaction product was analyzed by means of a 31P-NMR spectroscopic method. It was found that ATMP was formed with a yield of 59.1 percent.Additional ATMP preparations were conducted thereby using the method set forth in and conducting the reactions in accordance with that except that the methanesulfonic acid catalysts were utilized in the following levels. Example g mole(s) 2 61.85 0.644 3 42.33 0.441 The reaction product formed, analyzed as described in Example 1, showed a yield of ATMP of 76.8 percent Example 3 72.7 percent. These Examples (1-3) demonstrate the unexpected benefits of the inventive technology and show that the aminopolymethylene phosphonic acids can be prepared under exclusion of hydrohalogenic reactants in a short cycle time and in high yields as compared to state-of-the-art methods using the PClAdditional aminotrimethylene phosphonic acid compounds, Examples 65-67, were prepared by reacting the listed ingredients in the stated proportions thereby applying the sequence set forth in Example 1. Reactant g mole(s) Phosphorous acid 68.88 0.84 Water 10.0 Ammonia (32 percent solution) 14.87 0.28 Formaldehyde (36.6 percent solution) 72.3 0.882 The acid catalyst was used in the following proportions. Catalyst Example N° g mole(s) Methanesulfonic acid 65 2.016 0.021 Methanesulfonic acid 66 10.08 0.105 Ortho-phthalic acid 67 46.51 0.28 The reactants, except the formaldehyde, were added to the reactor at the start at room temperature. This reaction mixture was then heated to 125 °C at which temperature the gradual addition over a period of 30 minutes of the formaldehyde was started. The reaction was conducted in a closed vessel under autogeneous pressure built up. The reaction products, analyzed thereby using the method of Example 1, showed that the following compounds were formed. Example percent-ATMP percent-N-MeIBMPApercent-HExample 1.; Aminotrimethylene phosphonic acid (ATMP) was prepared by reacting phosphorous acid, ammonia and formaldehyde in the presence of a methanesulfonic acid catalyst. The individual components were used in the recited proportions. Reactant g mole(s) Phosphorous acid 100.45 1.225 Methanesulfonic acid 15.43 0.161 Ammonia (25 percent solution) 27.2 0.4 Formaldehyde (36.6 percent solution) 103.27 1.26 Water 58.07 - The phosphorous acid was first added to the reactor followed by the water, the methanesulfonic acid and the ammonia. The reaction mixture so prepared was subsequently heated to 105 °C at which temperature the gradual addition of the formaldehyde was started. The formaldehyde was added in a period of 2 hours. The reaction was, after the addition of the formaldehyde, continued under reflux conditions for a further period of 2 hours. The reaction product was analyzed by means of a 31P-NMR spectroscopic method. It was found that ATMP was formed with a yield of 59.1 percent.Additional ATMP preparations were conducted thereby using the method set forth in and conducting the reactions in accordance with that except that the methanesulfonic acid catalysts were utilized in the following levels. Example g mole(s) 2 61.85 0.644 3 42.33 0.441 The reaction product formed, analyzed as described in Example 1, showed a yield of ATMP of 76.8 percent Example 3 72.7 percent. These Examples (1-3) demonstrate the unexpected benefits of the inventive technology and show that the aminopolymethylene phosphonic acids can be prepared under exclusion of hydrohalogenic reactants in a short cycle time and in high yields as compared to state-of-the-art methods using the PClExample 2.; Further amino polymethylene phosphonic acids were prepared by reacting in the operational sequence of Example 1, except for the duration of the formaldehyde addition, the listed materials as follows: Reactant g mole(s) Phosphorous acid 100.45 1.225 Amberlyst 15 wet resin 125.0 Ammonia (25 percent-solution) 27.2 0.4 Formaldehyde (36.6 percent-solution) 103.27 1.26 The formaldehyde was added, starting from 105 °C, under distillation, over a period of 2 hours and 30 minutes. The reaction product analyzed thereby using the method of showed the following major component levels. ATMP 62.7 percent; N-MeIBMPA 8.4 percent; andHExample 1. Aminopolymethylene phosphonic acid compounds were prepared by reacting the listed ingredients in the stated proportions. Reactant g mole(s) Phosphorous acid 301.35 3.675 Amberlyst 36 dry 150.0 Ammonia (25 percent-solution) 81.6 1.2 Formaldehyde (36.6 percent-solution) 309.9 3.78 A mixture of the phosphorous acid, the Amberlyst 36 and the ammonia is heated up, under stirring, to 105 °C starting from which temperature the formaldehyde was gradually added, under distillation, over a period of 4 hours and 20 minutes. The reaction product was analyzed with a 31P-NMR spectroscopic method. It was found that major levels of aminotrimethylene phosphonic acid (ATMP) and N-methyleneimino bis(methylene phosphonic acid) (N-MeIBMPA) were present in the reaction product, as follows: ATMP 67.5 percent; N-MeIBMPA 6.3 percent; andH

Molecular Weight:139.09
XLogP3:-4.5
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:139.03983018
Monoisotopic Mass:139.03983018
Topological Polar Surface Area:83.6
Heavy Atom Count:8
Complexity:98.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes