TW314522B - - Google Patents

Description

314522 Α7 Β7 Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Description of the invention () The present invention relates to a method for preparing aminophosphonic acid. Aminophosphonic acid is a known compound and a useful intermediate in the preparation of agricultural chemicals. In particular, various methods have been described for converting aminomethylphosphonic acid into a N-Asia® carboxymethylglycine and its salts. For example, a typical preparation method can be found in US Patent No. 4,094,928, which describes the reaction of aminoformic acid or its alkyl ester with glyoxal or glyoxylate to form carbonylaldimine iminomethylphosphonate, and By reduction and hydrolysis, it is converted into N-phosphorous carboxymethylglycine. There are many other published methods for preparing K-phosphoramidylcarboxymethylglycine using aminophosphonic acid as a starting material. However, the commercial development of this type of manufacturing method is still limited by the lack of an economical way to manufacture the starting material aminomethyl phthalic acid. The present invention provides a method for manufacturing aminomethoric acid using low-cost and easily available starting materials. In addition, in addition to the required methacrylic acid, the main product of this method is carbon dioxide, so this method is beneficial to environmental protection. According to the present invention, there is provided a method for producing aminomethylphosphonic acid, which comprises ai under conditions of no water and non-oxidation on the spring, in _, chlorinated hydrocarbons, aromatic solvents, eye or anhydrous carboxylic acid or In the presence of the solvent of its ester, the compound with the most stoichiometric formula R-C Η 2 -N Η -C 0 -N Η -C Η 2 -R 'with a spring is reacted with an acidifying agent, where R and R' It is the same and represents hydroxy or alkoxy, and the phosphorylating agent is: (i) SS trichloride, (ί ί) K acid, Kun Yiding-line-(please read the notes on the back before filling in this Page) This paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (2l〇xf97mm) 314522 A7 B7 V. Description of invention () Ministry of Economic Affairs Central Standards Bureau employee consumption cooperation du printing ui Γ) dioxin dioxin Ester, Π V) compound of formula (VI) (C 1) „P (0 R 1) 3-η (VI) or a mixture of these compounds, where η is 1, R 1 is Ci-7 alkyl, Or (v) a mixture of phosphorus trichloride and an alcohol of formula R 1 ΟΗΗ, wherein R 1 is as defined above, and 1.8 to 2.2 moles of POH alcohol are used per mole of phosphorus trichloride »-Ran After b) the product of step (a) is hydrolyzed to form limpidic phosphonic acid. The back grinding (a) is carried out at a temperature of 0 10 to 50 C, and the hydrolysis reaction (b) is carried out at 100 C to It is carried out at a temperature of 200 t, and the pressure is adjusted accordingly. Although: the invention is not limited by any particular theory, it is still believed that the compound R-CH2-HH-C〇-NH-CH2-R '[formula (1)} and phosphoric acid The reaction of the chemical agent is the reaction of the R and R 'to produce a phosphorylated or partially phosphorylated gland intermediate * This intermediate is hydrolyzed to aminomethylphosphonic acid in step (b). Scheme 1 below illustrates dimethylol The reaction of dolphins with phosphorus trichloride, Scheme 2 illustrates the reaction of dimethylol urea with chlorooxynthoxydimethyl, which will be described in detail below. Suitable R groups include halogen, hydroxyl, Ci-4 Alkoxy (such as methoxy, ethoxy, and butoxy). But generally speaking, from a commercial point of view, the hard-to-remove group of Jane is better, and KR and R 'are both hydroxy dihydroxy Methyl dolphin is ^ clothing line (please read the precautions on the back before filling in this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210_ 乂 is 7 Shili) A 7 B 7. Fifth, the invention description () The Ministry of Economic Affairs Central Standards Bureau employee consumer cooperatives printed excellent starting materials. In the phosphorylating agent of formula (VI), η is preferably 1. n is 1 of formula (VI) The compounds are known and can be explained by various names that are not important, including phosphorus dichlorinated dialkyl esters, chlorophosphite dialkyl esters and chlorophosphonate dialkyl esters. Such compounds are referred to herein as chlorine Dialkyl phosphonates, such as diethyl chlorophosphonate. The R1 group is an unsubstituted Ck alkyl group such as methyl> ethyl * propyl, butyl, and it groups. The compound of formula (Π) can be easily prepared with tridonium phosphate and R 1 ΟΗ alcohol. For example, the compound of formula (VI) where η is 1 can be prepared by reacting the alcohol of the second ear with 1 mol of phosphorus radon. Although the compound of formula (VI) can be isolated from the mixture of R 1 Ο Η alcohol and phosphorus tridonate, and later used as a phosphorylating agent, the alcohol of phosphorus trichloride and the formula ΡΗΗ itself can also be used as a phosphorylating agent, The preferred usage ratio is as described above. ® The properties of the various substances in the mixture during the acidification reaction may be complicated. The scope of the present invention is not affected by the specific substances in the mixture of phosphorous trichloride used as the phosphorylating agent and the enzyme of formula R 1 0 Η (regardless of the formula ( V Π compounds or other compounds). If necessary, you can first remove the hydrochloric acid generated in the reaction, such as spraying non-oxidizing gas (such as nitrogen) to remove hydrochloric acid. SS acid can be combined with acetic acid and acetic anhydride It can be used as a suitable phosphorylating agent. Dialkyl phosphite can also be used as a phosphorylating agent, but we found that this reaction requires 100 ton high turbulence to have a reasonable product yield, and the better phosphorylating agent There is an excellent output ridge under the Jiaojiao Fengfeng. Binding Line 2 (please read the precautions on the back before filling in this page) This paper wave scale is applicable to the Chinese National Standard (CNS) A4 specification Uioxh7 mm) Ministry of Economic Affairs Printed by the Central Bureau of Standards' Staff Consumer Cooperative 314522 A7 B7 Fifth Invention Description () Η phosphorous chloride or chloroxy hypophosphorous acid dioxin, such as diethyl oxyhypophosphite or dibutyl oxyhypophosphite, or three atmospheres Phosphorus and alcohol (such as ethanol or Butanol) is a particularly good phosphorylating agent. The reaction step (a) is carried out under anhydrous and non-oxidizing conditions. If necessary, the inversion step (a) can be carried out in the absence of a solvent. The former problem is that the phosphorylating agent itself can dissolve or suspend the compound of formula U) and can become an effective reaction medium. If necessary, an excessive amount of phosphorylating agent M can be used as the reaction medium, for example, to reduce the viscosity of the medium and make it easy to mix or vibrate ° or anhydrous solvents can also be used in combination with the phosphorylating agent. A suitable solvent is inert under the reaction conditions, and it is not reactive with phosphorylating agents. Such suitable solvents include ketones, chlorinated hydrocarbons, aromatic solvents, nitriles, and anhydrous carboxylic acids and their esters. Particularly preferred solvents are nitriles * such as acetonitrile, benzonitrile, acetonitrile, and nitrile, and carboxylic acids such as acetic acid and ethyl formate. Mixtures of such solvents can also be used, such as a mixture of ethyl formate and acetic acid. The use of a solvent that is not miscible with water has the advantage of later separation of the aminophosphonic acid product. Details will be described later. To provide a removable medium and make it easy to stir, it is preferred to use at least 1 part (weight to cost ratio) of solvent per 1 part (g-most) compound of formula (I). Yes K, the better reaction solvent is 1 part (weight ratio) of the compound of formula (I) 1 part (g ratio) solvent to 1 part (weight ratio) of the compound of formula (I) 20 parts (weight most) Solvent. It is not economical to use super-most solvents, preferably 5 parts (weight per 1 part (weight-most ratio) of formula (Π compound 1 part (M-most ratio) solvent to 1 part (weight-to-weight ratio) formula Π) compound Ratio) solvent. . Reaction step U) is carried out between 0 t and 50 t, but we found that the reaction can be carried out slowly at -30C in a suitable solvent (such as ethyl chloride). The size of this paper is applicable to the Chinese National Standard (CNS> A4 specification (210 X 297 mm) Binding I binding] line V-(please read the precautions on the back before filling in this page) A 7 B7 V. Description of invention () Ministry of Economic Affairs Printed by the Staff Consumer Cooperative of China National Bureau of Standards-Generally speaking, the temperature of reaction step (a) is higher than 5 Ο υ without special advantages, this temperature will lead to a reduction in output ridge. Cool to maintain the desired temperature. Although the phosphorylating agent or the compound of formula (I) in step (a) may be in excess, the reactants are preferably K stoichiometric proportions. As mentioned above, assuming that you need to use ® acidulant as the reaction solvent, a larger excess of phosphorylating agent can be used. The hydrolysis step (b) can be carried out by adding water to the reaction medium formed in step (a). After the solvent K is compatible with water. If necessary, acid or base M can be added to accelerate the hydrolysis step. • Acid hydrolysis is preferred, for example with dilute mineral acids > such as hydrochloric acid. More conveniently, the acid hydrolysis is carried out at an acid strength of 碡 物 of 0 to 36¾ (weight ratio). If phosphorus trichloride is used as the phosphorylating agent, no acid needs to be added in the hydrolysis step, because the acid is already generated in step (a). This acid is believed to be the result of phosphorylation or partial acidification to produce porpoise intermediates (Scheme 1). When a solvent compatible with water is used in the reaction step (a), the addition of water or acid will cause the intermediate phosphorylation product of Scheme 1 (II) and the intermediate SS acidification product of Scheme 2 to move to the aqueous phase. The aqueous phase can be separated from the organic phase, so that the hydrolysis step can be carried out in the aqueous phase, and the organic phase can be recycled as needed. When the reaction (a) is carried out in a water-miscible solvent, it may be necessary to separate the solvent before the hydrolysis step ib) is completed, and K is incompatible with water to replace it, Μ promotes the recovery of the solvent and cycle. Therefore, for example, a solvent that is compatible with water can be removed by distillation and replaced with a solvent that is incompatible with water. If the boiling point of the water-insoluble solvent is higher than that of the water-miscible solvent and no azeotrope can be produced, the water-insoluble solvent can be added before or during distillation -------- -^ ------.- IT ------ A 2 (Please read the precautions on the back before filling in this page) This paper size is applicable to China National Standard (CNS) Α4 specification (210X 297mm ) Printed 314522 by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. V. Inventive () agent, w maintains an effective volume of 1 and helps to remove virtually all solvents that are compatible with water. For example, if the solvent that is incompatible with water is acetonitrile, add dimethyl & or jin · qing ’to heat the compound to the boiling point of acetonitrile, remove the acetonitrile and recycle it. Add water or acid to extract the phosphorylated intermediate into the aqueous phase to prepare for the next step of hydrolysis or hydrolysis. The solvent phase that is not miscible with water is also available for subsequent recycling. The hydrolysis step (b) shown in Scheme 1 and Scheme 2 is a single step. In fact, the it line of hydrolysis is a one-step process as shown in Scheme 3. Step (i) is easy to perform under the conditions of Heyi, for example, it can be contacted with water under the surrounding strips, and it can be probed under the surrounding impact force-it can be carried out. Step (π) requires more severe conditions as described below. We have found that in some environments, and when the solvent that is compatible with water is to be removed, before removing the solvent that is compatible with water, add enough water αρ up to 10,000; a phosphorylated intermediate (〗 [) or ( π,) 4 cumin water) is conducive to the progress of step U) hydrolysis, it is also conducive to the substitution of water-insoluble solvents w * such compounds (〗 ν) (non-compounds (〗 〖) or (丨),) ) It still exists when the solvent that is compatible with water is removed by steaming, and it can be extracted into the water phase later to complete the hydrolysis. Another method is to use alcohols, such as Cl_7 alkyl alcohols, such as R10H or higher alcohols, such as CsSCu alcohols, such as 2-ethylhexyl alcohol, instead of water (Scheme 4), in the process of removing the water-soluble solvent by distillation K That is, there is compound (V) (non-compound U ί)), which is extracted into the aqueous phase after the threshold to complete the hydrolysis. The process of distilling off the solvent that is compatible with water (according to scheme 丨, 2, 3 or 4), the choice of the compound present makes the preparation method quite flexible, which can be borrowed, for example, the boiling point of the compound in a solvent that is not compatible with water Relative thermal stability at the time _-λ-—___________-__ The paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (210X297mm) ---------- 1— (Please read the notes on the back first (Fill in this page again) Order-line _ A7 B7 V. Description of invention () Print control of the employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. The hydrolysis step (b >, whether it is step U as described in Schemes 1 and 2) and (the combination of i U, or the separate method of step (ii) as described in Schemes 3 and 4, is tied to 100 t Between 200 and 200 t, such as 1 5 (ΓΌ, the pressure is also adjusted. Carbon dioxide will be generated during hydrolysis (Scheme 1), and should be discharged during the hydrolysis process. It is preferable that each mole of the entire hydrolysis process ( I) Add 5 to 50 moles of water to the starting material. If necessary, you can add more water, but too much water will make the subsequent separation steps more difficult. Generally, it is better to add a minimum amount of water, as long as It suffices to hydrolyze and dissolve the reaction product. The compound of formula U) is known and can also be prepared in a similar way to prepare known compounds. For example, dimethylol urea can be easily prepared by reacting urea with formaldehyde The compound of formula (I) supplied to the reaction may be a dry solid, or a solution or sludge in an anhydrous solvent * such as a solution or sludge in the solvent used in the reaction step (a). Hydrolysis step (b) The product is generally an aqueous solution containing aminophosphonic acid. The aminophosphonic acid can be used by those skilled in the art. The method is recovered from an aqueous solution, for example, by crystallization. However, the aminophosphonic acid prepared by the present invention is generally a starting material for further reaction, for example, the starting material for the preparation of N-methylene-6 «carboxymethylglycine. Aminomethylphosphonic acid water-soluble is often a suitable raw material for further reactions, and if necessary undergoes an intermediate purification step. In this case, it is not necessary to separate the aminomethyl phthalic acid product from the aqueous solution. Is K, root Another aspect of the present invention is to provide a preparation method in which the amino acid is further reacted with K to prepare N-phosphoramidyl carboxymethylglycine 1 button binding,-line V-(please read the back side first Note: Please fill out this page again.) This paper scale is applicable to the Chinese National Standard (CMS) A4 specification (210 X 297 mm) A7 B7 V. Description of invention () The Ministry of Economic Affairs Central Standards Bureau employee consumption cooperative printed acid, no need to Separated from the aqueous solution. As mentioned above, in the reaction step (a) when two water-insoluble solvents are used or in step (a) when a water-miscible solvent is used and then replaced with a water-insoluble solvent , The solvent phase that is not miscible with water is It is recycled on the basis of ore or semi-connected pump for the next reaction step (a). When using the compound of formula (VI) or the mixture of phosphorus trichloride and alcohol as the phosphorylating agent, one product of hydrolysis is POOH alcohol (scheme 2) If ί ^ ΟΗ is a water-insoluble alcohol, such as alcohol derived from (: 4 or (: 5 alkyl groups (respectively butanol and amyl alcohol), it is possible to separate the alcohol for recycling If necessary, the lower alcohol can also be recovered for recycling by another method, such as the steam feeding method of the hydrolysis step. The order of adding the reactants in step (a) can be changed if necessary. For example, It is convenient to add the compound of formula (Π and phosphorylating agent to the solvent. But it is also possible to add the phosphorylating agent to the solution or mud of the compound of formula (I) in the reaction solvent, or the compound of formula (I) The solution or sludge is added to the solution of the phosphorylating agent in the reaction solvent. When the compound of formula (V [) is used as the phosphorylating agent * and when the compound of formula (VI) is prepared by the reaction of tridonated δδ and R 1 0 Η alcohol on site, it is not necessary to make it before adding it to the reaction medium Compound of formula (VI). For example, phosphorus radon can be added to the reaction solvent, followed by alcohol. The following spring examples of the invention K illustrate that in each example, all parts and percentages are weight ratios unless otherwise stated. Example 1 Fill 25.7g (0.18 丨 g Cumulus triphosphonate) into 250ml round -10 ~ The paper size is applicable to China National Standard (CNS) Α4 specification (210Χ 297mm) Approval of clothing line Two (please read the precautions on the back before filling this page) A 7 B7 V. Invention description () Ministry of Economic Affairs Central Standards Bureau employee consumption cooperation Du printed bottom flask, and began to stir. Add 10 grams of dimethylol gland (0.083 grams of mole) with stirring over 30 minutes. The addition of 10 g (0.07 3 g mol) of phosphorus trichloride makes the reaction mass easy to stir and the reaction is allowed to proceed at ambient temperature for 3 hours. Add 20 grams of anhydrous acetic acid (0.33 3 grams of mole), heat the reaction to 50 t, and maintain this temperature for 3 hours. The temperature was raised to 100 C * again and maintained for 4 hours. The reaction was then cooled to 60 ° C and water (50 g) was added over a period of 15 minutes on K. Reheating the K to generate reflux (1 0 4 t :), and maintained for 20 hours. Analysis of the resulting aqueous solution showed the presence of aminomethyl phthalic acid, yielding more than 50% °. · When Example 2 Loaded acetonitrile (100 g, 2. 44 g Culm) into a vibrator, thermometer and concentrated 500 ml round bottom flask. The device is flushed with chlorine gas and the solvent is cooled to 10 υ. The dimethylol (51.6 g, 0.409 g Cumulus) and o-trichloride (105.9 g, 0.766 g Mohr) were added in ten equal portions over 3 hours while stirring. The antidote was stirred at the surrounding temperature for 16 hours, after which the dimethylol dolphin that had originally formed into a sludge was completely dissolved. Slowly add water (27 g) while maintaining the temperature at 30D. The reaction was heated to the temperature of distilling the umbilical cord with sufficient K under atmospheric pressure, and dimethicone was added slowly during the distillation). Add water (100g), and separate the bottom aqueous phase containing bis (phosphoranylocarboxymethyl) (compound (IV) in Scheme 3). Add dilute hydrochloric acid (200ml, 3.65¾ weight / weight strength) to the aqueous phase ), Heated to 1550 under sufficient pressure] 10 hours, and regularly discharge the pressure tank _ _ 11 ~ _ This paper size is applicable to the Chinese National Standard (CMS) Α4 specification (210X297 mm) binding, Λ ^ .1 '(please read the precautions on the back before filling out this page) ^ 14522 Central Standards Bureau of the Ministry of Economic Affairs W: Printed by the Industrial and Consumer Cooperatives 5. Description of invention () Emission of carbon dioxide produced. Production of phosphinomethylphosphonic acid JM. NMR analysis determined 85%, and MHPLC measured 83-2%. Example 3 Ding Qing (20g) was loaded into a 100ml round-bottomed eel bottle equipped with a vibrator, thermometer, and concentration device Medium. The device is flushed with chlorine gas, and the solvent is cooled to 0¾. Jiang Dimethylol (0.3 g, 95¾ concentration) and phosphorus trichloride (21.3 g) are added in five equal portions in about 1 hour. Phosphorus trichloride was added for each addition, and dimethylol .. urea was added after ten minutes K. The reaction was stirred overnight at room temperature, then heated to 5 5 = 0, and maintained at this temperature for 1 hour. Add water (20g), and the precipitate formed immediately dissolves in the excess water. Separate the colorless nitrile layer and the clear bis (phosphonocarboxymethyl) urea-soluble layer. M NMR determined that the yield of bis (phosphoramidite) urea was 80 SK. The method of Example 1 hydrolyzes the water layer to obtain a quantitative product of aminophosphonic acid. Case 4 Repeat the process of Case 2 and use acetic acid and ethyl formate as water-soluble solvents. KHMR determination, when using acetic acid as the solvent, the yield of bis (phosphonomethyl) is 70 S ;. As shown in Example 1, the water layer was hydrolyzed and the parent compound was converted to aminomethylphosphonic acid. In the K N M R determination, the yield of bis (phosphonomethyl) gland was 5 OX when ethyl formate was used as the solvent. As shown in spring example 1, hydrolyze the water layer and convert it to aminophosphonate. -12-This paper scale is applicable to the Chinese National Standard (CNS) Α4 specification (210X297mm) I Approved Clothing Order * ',-(Please read the precautions on the back before filling this page) Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Printed A7 B7 V. Description of invention ()

Official Example FS Repeat the procedure of Example 3 * Toluene, benzyl eye, propyl eye and 2-methylglutaronitrile were used as water-insoluble solvents, respectively. In the K N M R determination, the yield of the bis (phosphonite methyl) gland was 20¾ when toluene was used as the solvent. For the determination, the yield of bis (phosphinic acid methyl) gland when using benzyl eye as a solvent was 503 ;. In the K N MR measurement, the yield of bis (phosphonite methyl) urea was 80% when using acetonitrile as the solvent. K determination * The yield of bis (phosphonomethyl) porpoise is 40% when using 2-methylglutamine as a solvent. In each case, as shown in Example 1 above, the water layer was hydrolyzed to quantitatively convert to aminomethylphosphonic acid.

Cellar Example R Place phosphorus trichloride (23.4g) and acetonitrile (100g) in a 250ml flask. Add dimethyl ether of dimethylolurea in batches (compound of formula (I), where! Both are-CH2-〇CH3) (12.3 g). The mixture was stirred at the side temperature for 18 hours, then heated to 50 C and maintained at this temperature for 2 hours. A white precipitate was formed and hydrogen gas was discharged. The mixture was heated to reflux * and maintained at this temperature for 2 hours. The mixture was distilled to remove acetonitrile, and near the end of the distillation, 30 ml of xylene was added. The mixture was flooded with 60 grams of water and then divided into two layers. The water layer was distilled in vacuo to remove water (40 g) to obtain a solid product. • Dissolve this product in 40 grams of water and 11.9 grams of 36¾ hydrochloric acid and heat to reflux under ambient pressure. (In a commercial spring practice, it is not necessary to remove water from the water layer to make a solid, and then add water. What K does in this example is to remove hydrochloric acid in steamed rice, and then hydrolyze with hydrochloric acid of known concentration). The hydrolysis was completed in more than 8 days, and the yield of aminomethylphosphonic acid was determined by HPLC to be 48.3%. _- 13 -_ This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) — Binding line-(please read the precautions on the back before filling this page) A7 B7 V. Description of invention () Economy Example 7 Printed by the Ministry of Central Standards Bureau Negative Consumers Cooperative Use compound of formula (I) (where R and R 'are the same, -C Η 2-0-C 4 H g) as the starting material, and repeat the process of Example 6. Η P L C determined that the output of aminophosphonic acid was 35.5%. Example ft A solution of 32.8 grams of phosphoric acid in 60 ml of acetic acid was added dropwise to 112.2 grams of acetic anhydride under cooling over a period of 1 hour. Add dimethylolurea (24 g) in batches over 50 minutes * while maintaining the temperature at 10 to 15 t. This solution was stirred at 10 t for 20 min. Then, the reaction mixture was added to the rollers, and the temperature was maintained at this temperature for 2.5 hours. After cooling to room temperature, add 2.2 g of water dropwise, while cooling, and maintain the temperature between 2 5-3 0 = C. The solution was then cooked to roll back and maintained at this temperature for 2 hours. After cooling, the acetic acid was removed by vacuum distillation to obtain an off-white solid. This solid was dissolved in water (40 g) and hydrochloric acid (U. 9 g 36¾ solution) and heated to reflux under ambient pressure. After 7 days, the hydrolysis was completed, and HP LC determined that the output stems of methacrylic acid were 17.8%. When Example 9 repeats the process of Example 8, except that the hydrolysis is carried out under alkaline conditions. The bis (phosphoramidite) porpoise solution (82.7 g, 30¾ strength; 0.1 g Cumulus) and the sodium hydrazide solution (51.1 g, 47% strength; 0-6 g Cumulus) were heated at 100Ό for 120 hours . Yield 10,5 g of dina salt of aminomethyl phthalic acid (K loaded with bis (sub-fig carboxymethyl) urea-based yield of 9 5: S). _-14-_ This paper scale is applicable to China National Standard Falcon (CNS> A4 specification (210 > < 297mm) --------- ^ ------ 1T ------ 0 Two (please read the precautions on the back before filling this page) 314522 Printed by the Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of Invention () In Example 10, add dimethylol dolphin (6 grams) to Bichai ( : 100 mL), then add diethyl chlorophosphinate (1.565 g) dropwise with cooling and mixing for half a hour K. After all dimethylolurea is dissolved in the solution Afterwards, the mixture was clear. Add water (50 litres 1 and hydrochloric acid (10 ml, 0.1 M), then heat the flask to distill acetonitrile. Add two parts (30 ml each) of ethanol to the azeotrope with water In the middle, further distillation, and then the mixture was heated to reflux under atmospheric pressure. After 7 days of rolling back, the hydrolysis was completed, and the yield of aminophosphonic acid determined by K phosphorus HMR was 88%. -W._Ά_LL 将 乙 _ (2 5 milliopens) Loaded into a flask equipped with a contractor, thermometer, vibrator, and dropping funnel, and cooled together to 0 to 10. Add phosphorus trichloride (7 g), then slowly add ethanol for more than half an hour 4.6 g), while maintaining the temperature at 0-10 t. Allow the reaction mixture to rise to ambient temperature and stir for 3 hours. Vacuum distillation to remove acetonitrile. Add water (50 ml) and mix the water mixture at atmospheric pressure Heated to reflux for 1 hour. Obtained bis (SS carboxymethyl) urea (yield 蹤 80 0 J;), and converted to aminomethylphosphonic acid under the conditions of high quality. When Example 1? Repeat Example 1 1 process, but ketamine is substituted for acetonitrile. After the phosphorylation reaction is complete, add water (.50 ml) and separate the phases. Heat the aqueous phase to reflux for 1 hour at atmospheric pressure. Double bis sub-SS carboxylate Methyl) porpoise (output rate 6 9 S :), and at -15- gutter >-(please read the precautions on the back before filling in this page) This paper size is applicable to China National Standard (CNS) Α4 specifications (210X 297 mm) A7 B7 V. Description of invention () Printed by the employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, which is essentially optimized and converted into aminomethylphosphonic acid. Example 13 Repeat the spring 2 process to the original The dimethylol urea starting material of the sludge sample was completely dissolved. Then slowly add 2-ethylhexanol (20.0.7 ), While maintaining the temperature below 3Ot. The reaction was heated at atmospheric pressure to a temperature sufficient to distill acetonitrile. Add water (100g to heat the reaction to reflux for 2 hours. Then cool the reaction and separate the layers to obtain Aqueous bis (phosphoramidyl) gland solution, and then hydrolyzed by the method of Example 2. Example 14 Diethyl δδ acid diethyl ester (41.4 g) and dimethylol gland U0 g) were placed in a 100 mL Yan bottom flask Inside and heated to 1 2 0 " Ό. Heat and hold for 20 hours, during which a small amount of distillate (7.2 g) is collected. Distill excess diethyl sulfite under reduced pressure and fill with water (40 40 liters). The reaction was rolled back in the presence of 0.8 g of 3 6 X HCL for 2 hours. M N M R determined that the output ridge of the bis (bisphosphonocarboxymethyl) gland was 66¾. After hydrolysis, it was converted into aminomethylphosphonic acid at an essentially quantitative yield. When Example 15 was filled with phosphorus trichloride (7.0 g) in a 100 m.L round low flask, methanol (3.2 hr) was slowly added while maintaining the reaction temperature below 2 (Γ · 〇. Load Ding Jing (25 5 grandsons), and add dimethylol dolphin (3.3 g) in batches on a 30-point mirror K. _-16-_ This paper scale is applicable to the Chinese National Standard Falcon (CN'S) Α4 specification (210Χ 297mm) (please read the precautions on the back before filling this page) A7 B7 V. Invention description () Stir at room temperature overnight, add water (50 ml) and separate into two phases. The water phase was rolled back for 2 hours to obtain an aqueous solution of bis (phosphoramidylcarboxymethyl) urea with an output rate of 82%. After hydrolysis, it was converted into aminomethylphosphonic acid under essentially quantitative production. --------- 1 ------ IT ----- '0 2 (Please read the precautions on the back first and then fill out this page) Printed by the Employees Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs- 17- This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (2I0X297mm) 5. Description of the invention (Fang Lei A7 B7 chemical formula description 0 XH, .CH, HO, ΝΗ, ΝΗ ΌΗ (I) 2PC1- ΟII / CH2 οil

οCHjI

Cl—P, NH NH, P——cl + 2HC1

Cl (II)

Cl ----------- install ------ order ------- line (please read the notes on the back before filling in this page) 5H2〇 Employee Consumer Cooperative of Central Bureau of Standards, Ministry of Economic Affairs Print 〇2 HO——P——CH2-NHn 4HC1

CO 2

HO (III) -18- The scale of this paper is applicable to the Chinese National Standard (〔別) 8 4 specifications (210 ′ and 297 mm) > 14522 A7 B7 Fifth, the description of the invention (chemical formula (the description is 2 0, CH ,

, CH 2 HO, NH, NH ΌΗ (I) 2PC1 (0R1) 2 t o: o:

: p · l o R

H

H 'N: c

OHHT * H · N

CH

0R + 2HC1

OR

I I

OR o 2 H 5 ----------- installed ------ order ------- line-- (please read the precautions on the back before filling this page) Ministry of Economic Affairs Central Standards Printed by the Bureau ’s Consumer Cooperative Society 〇-II 2 HO—P—CH2-NH.

+ 4R1OH

CO 2 HO (III) • 19—This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297mm) V. Description of the invention (Part 3 R o

2 H

f r onnc I -H (1 'N A7 B7 chemical formula (for explanation)

ο / CHjI !, ΝΗ, Ρ——OR

OR o: r o o 2 H 4 ΟΜΠΡ ——c < — 'I c

-a. 1 ΟΠΜΜΤ——c 2 H c \ H N

OH: p

H p onnc

NH

CH o:: p o

OH

OH

VI ----------------- iT ------ 0-(Please read the precautions on the back before filling out this page) Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (Ii) h2o ▼ 〇I. 2 HO—P—-CH2-NH2 + CO2 HO (III) This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) V. Description of the invention (Scheme 4 A7 B7 Chemical formula (for illustration

+ 4HC1 -------- i ------, 1T ------ 0 (Please read the notes on the back before filling this page) Printed by the employee consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs i ο 2 Η 5 ο Η 2 ΟΠΜΡ. Ηό

I I I Η Ν 1 2 Ηc Ηο 1 R 4 02 C + 2 The size of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm)

Claims (1)

Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs ^ 14522 VI. Patent Scope 1 A method for the manufacture of aminomethylphosphonic acid, which includes: a) Under conditions that are substantially free of water and non-oxidizing, Yu Si, chlorine In the presence of a hydrocarbon, an aromatic solvent, a solvent of ophthalmic acid or anhydrous carboxylic acid or its ester, a formula of substantially stoichiometric ratio R-C Η 2-N Η-C 0-N Η-C Η 2-R ' The compound and the dish acidifying agent are inverted, wherein R and R 'are the same and represent hydroxyl or alkoxy groups, and the phosphorylating agent is: (i) phosphorus trichloride, _ (ii) phosphoric acid, Π ii) diphosphite Alkyl esters, f 'iv) formula ί VI) compounds (C!) „P (0 R1) 3-η (VI) or stick compounds of these compounds, where η is 1, is alkyl , Or ('ν) a mixture of phosphorus trichloride and an alcohol of formula R 1 〇Η, wherein R 1 is as defined above, and each mole of phosphorus trichloride uses 1.8 to 2.2 moles of R 1 0 H alcohol, then b ) The product of step (a) is hydrolyzed to produce aminomethylphosphonic acid, wherein reaction (a) is carried out at a temperature of 0T: to 50 °, and wherein hydrolysis reaction (b) is carried out at 100 ^ 0 to 200 ° temperature The pressure is adjusted accordingly. F -22--------- 1¾ .------ 1T ------ ^ (Please read the precautions on the back before filling this page) This paper scale applies the Chinese National Standard (CNS) A4 specification (210X297mm) ^ 14522 Bd. D8 6. Scope of patent application 2- The method of the first item in the scope of patent application, in which the reaction (a) is as complete For} generation (b agent of the instant dissolution step, the dissolving water phase is incompatible with the water, etc. ¾ enter the two agents in the armor, such as the dissolution of the jelly, and the water will come out and kiss: equal parts of the eye before forming acid. Phosphonic acid methylamine glycine group in the methyl amide, the phosphine method N- Fang Cheng's life should be 2 or step 11 first entry 'Fan Lili special application please do not apply based on the root of the product ---- -, 'Installed-- (please read the precautions on the back before filling in this page) Ί Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 3 2 This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 public daughter)