DE2702631A1 - Hydroxy-aminopropane-di:phosphonic acids prepn. - from beta-alanine or poly-beta-alanine and phosphorous acid-phosphorus oxychloride - Google Patents
Hydroxy-aminopropane-di:phosphonic acids prepn. - from beta-alanine or poly-beta-alanine and phosphorous acid-phosphorus oxychlorideInfo
- Publication number
- DE2702631A1 DE2702631A1 DE19772702631 DE2702631A DE2702631A1 DE 2702631 A1 DE2702631 A1 DE 2702631A1 DE 19772702631 DE19772702631 DE 19772702631 DE 2702631 A DE2702631 A DE 2702631A DE 2702631 A1 DE2702631 A1 DE 2702631A1
- Authority
- DE
- Germany
- Prior art keywords
- alanine
- beta
- hydroxy
- phosphorus oxychloride
- phosphorous acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 229940000635 beta-alanine Drugs 0.000 title claims abstract description 15
- XVNATSNNNSZLPC-UHFFFAOYSA-N P(O)(O)O.P(=O)(Cl)(Cl)Cl Chemical compound P(O)(O)O.P(=O)(Cl)(Cl)Cl XVNATSNNNSZLPC-UHFFFAOYSA-N 0.000 title 1
- 150000003009 phosphonic acids Chemical class 0.000 title 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 5
- 150000007513 acids Chemical class 0.000 claims abstract description 4
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 abstract description 5
- 229910019213 POCl3 Inorganic materials 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YHZCTZGJKHNVQY-UHFFFAOYSA-N 2-(diethylazaniumyl)propanoate Chemical compound CCN(CC)C(C)C(O)=O YHZCTZGJKHNVQY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical class [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- -1 diethylamino-1-hydroxypropane-1,1-diphosphonic acid Chemical compound 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229950011008 tetrachloroethylene Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
Description
Verfahren zur Herstellung von 1-Hydroxy-5-amino-propan-Process for the preparation of 1-hydroxy-5-aminopropane
1, 1 -diphosphonsäuren" Gegenstand der Erfindung ist ein verbessertes Verfahren zur Herstellung von 1-Hydroxy-)-amino-propan-l,l-diphosphonsäuren, wobei die Aminogruppe durch niedere Alkylreste substituiert sein kann. 1, 1 -diphosphonic acids "The invention is an improved Process for the preparation of 1-hydroxy -) - aminopropane-l, l-diphosphonic acids, wherein the amino group can be substituted by lower alkyl radicals.
Aus der deutschen Patentschrift 2 1)0 794 ist es bekannt, 1-Hydroxy-3-amino-propan-1,1-diphosphonsäure durch Umsetzung von ß-Alanin oder Poly-ß-Alanin mit einem Gemisch aus Phosphortrichlorid und phosphoriger Säure in Gegenwart oder in Abwesenheit eines organischen Verdünnungsmittels herzustellen. Vorzugsweise wird in Gegenwart eines organischen Verdünnungsmittels wie Chlorbenzol gearbeitet, um Schwierigkeiten beim Rühren des Reaktionsgemisches zu vermeiden. Bei der Umsetzung entstehen jedoch gelb-rote Nebenprodukte in Form von amorphen Phosphorsauerstoffverbindungen unbekannter Struktur, deren Abtrennung vor allem in Gegenwart von Chlorbenzol sehr aufwendig ist. Bei der Herstellung größerer Mengen ist zu berücksichtigen, daß diese Phosphorverbindungen gefährliche, leicht entzündliche Nebenprodukte darstellen.It is known from German Patent 2 1) 0 794 to use 1-hydroxy-3-aminopropane-1,1-diphosphonic acid by reacting ß-alanine or poly-ß-alanine with a mixture of phosphorus trichloride and phosphorous acid in the presence or absence of an organic diluent to manufacture. It is preferably used in the presence of an organic diluent how chlorobenzene worked to avoid difficulty stirring the reaction mixture to avoid. During the conversion, however, yellow-red by-products are formed of amorphous phosphorus-oxygen compounds of unknown structure, their separation is very expensive, especially in the presence of chlorobenzene. When making larger ones Quantities must be taken into account that these phosphorus compounds are dangerous, easily represent flammable by-products.
Es wurde nun gefunden, daß man diese Nachteile vermeiden kann, wenn man sich des nachstehend beschriebenen Verfahrens zur Herstellung von 1-Hydroxy-3-amino-propan-1,1-diphosphonsäuren bedient. Das neue Verfahren ist dadurch gekennzeichnet, dals man Poly-ß-alanin oder ß-Alanin, wobei die Aminogruppe durch niedere Alkylreste substituiert sein kann, mit einem Gemisch aus phosphoriger Säure und POS1» umsetzt und das Reaktionsgemisch anschließend hydrolysiert.It has now been found that these disadvantages can be avoided if follow the procedure described below for the preparation of 1-hydroxy-3-aminopropane-1,1-diphosphonic acids served. The new process is characterized in that one poly-ß-alanine or ß-alanine, the amino group being replaced by lower Substituted alkyl radicals can be, with a mixture of phosphorous acid and POS1 »and the reaction mixture then hydrolyzed.
Poly-ß-Alanin, welches aus Acrylnitril und Ameisensäure entsteht, wird bei dieser Reaktion zu ß-Alanin hydrolysiert, das dann weiter zur 1-Hydroxy-)-amino-propan-1, 1-diphosphonsäure reagiert.Poly-ß-alanine, which is formed from acrylonitrile and formic acid, is hydrolyzed in this reaction to ß-alanine, which is then further to 1-hydroxy -) - amino-propane-1, 1-diphosphonic acid reacts.
Außer ß-Alanin können auch als Ausgangsprodukte solche ß-Alanine verwendet werden, deren an der Aminogruppe befindlichen Wasserstoffatome ganz oder teilweise durch niedere Alkylreste wie Methyl-, Xthyl- oder Propylgruppen ersetzt sind.In addition to ß-alanine, such ß-alanines can also be used as starting products whose hydrogen atoms located on the amino group are wholly or partially are replaced by lower alkyl radicals such as methyl, ethyl or propyl groups.
Zweckmäßigerweise werden pro Mol ß-Alanin 0,5 bis 2 Mol, vorzugsweise 1 - 2 Mol, phosphoriger Säure sowie 0,5 bis 2 Mol, vorzugsweise 1 - 2 Mol, POCl) eingesetzt. Dabei hat sich gezeigt, daß POC13 teilweise, d. h. etwa bis zur Hälfte durch P205 ersetzt werden kann.Expediently, 0.5 to 2 moles, preferably, are per mole of β-alanine 1 - 2 mol, phosphorous acid and 0.5 to 2 mol, preferably 1 - 2 mol, POCl) used. It has been shown that POC13 partially, i. H. about up to halfway can be replaced by P205.
GewUnschtenfalls können Verdünnungsmittel wie Chlorbenzol, Tetrachloräthan, Tetrachloräthylen, Trichloräthylen oder Tetrachlorkohlenstoff verwendet werden, vorzugsweise wird Jedoch ohne VerdUnnungsmittel gearbeitet.If desired, diluents such as chlorobenzene, tetrachloroethane, Tetrachlorethylene, trichlorethylene or carbon tetrachloride are used, however, preference is given to working without a diluent.
Die Umsetzung erfolgt im allgemeinen bei Temperaturen zwischen 80 und 1300 c. Anschließend wird das Reaktionsgemisch durch Zugabe von Wasser hydrolysiert.The reaction generally takes place at temperatures between 80 and 1300 c. The reaction mixture is then hydrolyzed by adding water.
Aus der wäßrigen Lösung kristallisieren die 3-Amino-l-hydroxypropan-1,1-diphosphonsäuren aus. Die Ausbeute läßt sich noch durch Abtrennen der Mutterlauge und Versetzen mit Alkohol oder Aceton steigern.The 3-amino-1-hydroxypropane-1,1-diphosphonic acids crystallize out of the aqueous solution the end. The yield can still be achieved by separating off the mother liquor and adding it Increase alcohol or acetone.
Die anfallenden 1-Hydroxy-3-amino-propan-1 ,1 -diphosphonsäuren sind gute Komplexbildner, die auch in unterstöchiometrischen Mengen wirksam sind. Sie können daher in Reinigungs- oder Wasser^ behandlungsmitteln Anwendung finden.The resulting 1-hydroxy-3-aminopropane-1, 1 -diphosphonic acids are good complexing agents that are also effective in sub-stoichiometric amounts. she can therefore be used in detergents or water treatment agents.
Beispiel 1 In eine Mischung von 82,8 g (1 Mol) 99,0ige phosphorige Säure und 153,5 g (1 Mol) Phosphorylchlorid wurden langsam 89.1 g (0,5 Mo) 81,4die Diäthylaminopropionsäure eingetragen, wobei die Temperatur maximal auf 40° C anstieg. Nach der Zugabe wurde stufenweise auf 1000 C erhitzt und das Reaktionsgernisch 4 Std. bei dieser Temperatur belassen. Während dieser Zeit wurde das Produkt zunehmend viskoser und schließlich fest; jedoch wurden keine gelben "Phosphorpolymeren" gebildet.Example 1 In a mixture of 82.8 g (1 mol) of 99.0 phosphorous Acid and 153.5 g (1 mol) of phosphoryl chloride slowly became 89.1 g (0.5 mol) of 81.4 g Entered diethylaminopropionic acid, the temperature rising to a maximum of 40 ° C. After the addition, the mixture was gradually heated to 1000 C and the reaction mixture was 4 Leave at this temperature for hours. During this time the product grew more viscous and finally solid; however, no yellow "phosphorus polymers" were formed.
Nach dem Abkühlen wurden zur Hydrolyse 300 ml Wasser zugesetzt und die Lösung bis auf ein Gesamtvolumen von ca. 250 ml verkocht. Durch Eintropfen der Lösung in Äthylalkohol wurde die Diphosphonsäure ausgefällt. Es wurden 8).1 g = 57.1 ffi )-Diäthylamino-1-hydroxypropan-1,1-diphosphonsäure erhalten.After cooling, 300 ml of water were added for hydrolysis and the solution boiled down to a total volume of approx. 250 ml. By instilling the Solution in ethyl alcohol, the diphosphonic acid was precipitated. There were 8) .1 g = 57.1 ffi) diethylamino-1-hydroxypropane-1,1-diphosphonic acid.
Molgewicht lt. pH-Titration = 289.1; ber. 291 Schmelzpunkt: 2020 C gef. C 28.80 H 6.44 N 4.99 P 21.27 ber. 28.87 6.5) 4.81 21.31 Beispiel 2 Gemische von ß-Alanin mit H»PO) und POCl3 ( und ggfs. P205), die in unterschiedlicher Reihenfolge zusammengegeben werden können, wurden bei den in nachfolgender Tabelle angegebenen Molverhältnissen, Zeiten und Temperaturen umgesetzt. Das Reaktionsprodukt wurde anschließend mit der ausreichenden Menge Wasser in der Hitze hydrolysiert..Nach Abkühlen auf -5 bis +100 C wurde die auskristallisierte Diphosphonsäure abgetrennt. Durch Behandeln der Mutterlauge mit Fällungsmitteln wie Alkohol und Aceton läßt sich die Ausbeute noch merklich steigern. Die in der Tabelle angegebenen Ausbeuten sind ohne Fällung erhalten worden.Molecular weight according to pH titration = 289.1; cal. 291 Melting point: 2020 C found C 28.80 H 6.44 N 4.99 P 21.27 calc. 28.87 6.5) 4.81 21.31 Example 2 Mixtures of ß-alanine with H »PO) and POCl3 (and possibly P205), which are in different order can be combined, were given in the table below Molar ratios, times and temperatures implemented. The reaction product was then hydrolyzed with a sufficient amount of water in the heat Cooling to -5 to +100 C, the crystallized diphosphonic acid was separated off. By treating the mother liquor with precipitants such as alcohol and acetone leaves the yield increase noticeably. The yields given in the table have been obtained without precipitation.
Tabelle
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19772702631 DE2702631A1 (en) | 1977-01-22 | 1977-01-22 | Hydroxy-aminopropane-di:phosphonic acids prepn. - from beta-alanine or poly-beta-alanine and phosphorous acid-phosphorus oxychloride |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19772702631 DE2702631A1 (en) | 1977-01-22 | 1977-01-22 | Hydroxy-aminopropane-di:phosphonic acids prepn. - from beta-alanine or poly-beta-alanine and phosphorous acid-phosphorus oxychloride |
Publications (1)
Publication Number | Publication Date |
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DE2702631A1 true DE2702631A1 (en) | 1978-07-27 |
Family
ID=5999321
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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DE19772702631 Withdrawn DE2702631A1 (en) | 1977-01-22 | 1977-01-22 | Hydroxy-aminopropane-di:phosphonic acids prepn. - from beta-alanine or poly-beta-alanine and phosphorous acid-phosphorus oxychloride |
Country Status (1)
Country | Link |
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DE (1) | DE2702631A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0027982A1 (en) * | 1979-10-27 | 1981-05-06 | Henkel Kommanditgesellschaft auf Aktien | Process for preparing 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
EP0039033A1 (en) * | 1980-04-28 | 1981-11-04 | Henkel Kommanditgesellschaft auf Aktien | Process for preparing omega-amino-1-hydroxyalkylidene-1, 1-bis phosphonic acids |
EP0082472A2 (en) * | 1981-12-23 | 1983-06-29 | Henkel Kommanditgesellschaft auf Aktien | Process for the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
DE3535404A1 (en) * | 1984-10-29 | 1986-04-30 | Istituto Gentili S.P.A., Pisa | METHOD FOR PRODUCING DIPHOSPHONIC ACIDS |
US4608368A (en) * | 1984-07-13 | 1986-08-26 | Henkel Kommanditgesellschaft Auf Aktien | 1-hydroxy-1,1-diphosphonic acids and cytostatic use thereof |
US4711880A (en) * | 1984-08-06 | 1987-12-08 | Ciba-Geigy Corporation | Crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate |
US4942157A (en) * | 1986-07-11 | 1990-07-17 | Boehringer Mannheim Gmbh | 1-hydroxy-3-(N-methyl-N-propylamino)propane-1,1-diphosphonic acid, pharmaceutical compositions and methods of use |
WO2005063779A2 (en) * | 2003-12-23 | 2005-07-14 | Lyogen Limited | A process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof |
US7612229B2 (en) | 2003-01-28 | 2009-11-03 | Richter Gedeon Vegyeszeti Gyar Rt. | Industrial process for the synthesis of 2-substituted 1-(hydroxy-ethylidene)-1,1-bisphosfi- conic acids of high purity and the salts thereof |
-
1977
- 1977-01-22 DE DE19772702631 patent/DE2702631A1/en not_active Withdrawn
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0027982A1 (en) * | 1979-10-27 | 1981-05-06 | Henkel Kommanditgesellschaft auf Aktien | Process for preparing 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
EP0039033A1 (en) * | 1980-04-28 | 1981-11-04 | Henkel Kommanditgesellschaft auf Aktien | Process for preparing omega-amino-1-hydroxyalkylidene-1, 1-bis phosphonic acids |
US4407761A (en) | 1980-04-28 | 1983-10-04 | Henkel Kommanditgesellschaft Auf Aktien | Process for the production of ω-amino-1-hydroxyalkylidene-1,1-bisphosphonic acid |
EP0082472A2 (en) * | 1981-12-23 | 1983-06-29 | Henkel Kommanditgesellschaft auf Aktien | Process for the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
EP0082472A3 (en) * | 1981-12-23 | 1984-03-21 | Henkel Kommanditgesellschaft Auf Aktien | Process for the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
US4608368A (en) * | 1984-07-13 | 1986-08-26 | Henkel Kommanditgesellschaft Auf Aktien | 1-hydroxy-1,1-diphosphonic acids and cytostatic use thereof |
US4711880A (en) * | 1984-08-06 | 1987-12-08 | Ciba-Geigy Corporation | Crystalline disodium 3-amino-1-hydroxypropane-1,1-diphosphonate pentahydrate |
DE3535404A1 (en) * | 1984-10-29 | 1986-04-30 | Istituto Gentili S.P.A., Pisa | METHOD FOR PRODUCING DIPHOSPHONIC ACIDS |
US4942157A (en) * | 1986-07-11 | 1990-07-17 | Boehringer Mannheim Gmbh | 1-hydroxy-3-(N-methyl-N-propylamino)propane-1,1-diphosphonic acid, pharmaceutical compositions and methods of use |
US7612229B2 (en) | 2003-01-28 | 2009-11-03 | Richter Gedeon Vegyeszeti Gyar Rt. | Industrial process for the synthesis of 2-substituted 1-(hydroxy-ethylidene)-1,1-bisphosfi- conic acids of high purity and the salts thereof |
WO2005063779A2 (en) * | 2003-12-23 | 2005-07-14 | Lyogen Limited | A process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof |
WO2005063779A3 (en) * | 2003-12-23 | 2005-09-29 | Lyogen Ltd | A process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof |
US7723542B2 (en) | 2003-12-23 | 2010-05-25 | Trifarma S.P.A. | Process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof |
EP2206717A1 (en) * | 2003-12-23 | 2010-07-14 | Alchymars S.p.A. | A process for the preparation of alkyl- and aryl-diphosphonic acids and salts thereof |
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